Accuray Exchange Showcase: 2024 Conference Highlights

3rd-7th, February 2025

Missed the opportunity to watch the AEx Showcase live? Catch-up at your convenience:

Day 1: CNS Indications
Day 2: CNS Indications
Day 3: Breast and Gynecological Cancers
Day 4: Thorax and Rare Indications
Day 5: Genitourinary and Gastrointestinal Cancers

Watch the highlights now:

An opportunity to dive deep into topics related to clinical research on CyberKnife®, TomoTherapy®, and Radixact® Systems.

If you cannot access ON24, please use the following links. Day 1 Day 2 Day 3 Day 4 Day 5

Mon, Feb 3rd
Tues, Feb 4th
Wed, Feb 5th
Thurs, Feb 6th
Fri, Feb 7th

Day 1: CNS Indications

Chaired by:

Alfredo Conti, M.D., Ph.D., FEBNS,
University of Bologna, IRCCS Institute of Neurological Sciences of Bologna, Italy

4:00 PM

Welcome

Presenter: Alfredo Conti, M.D., Ph.D., FEBNS (University of Bologna, IRCCS Institute of Neurological Sciences of Bologna, Italy)

4:05 PM

Frameless Radiosurgery Is a Safe and Effective Treatment for Medically-Refractory Trigeminal Neuralgia in Elderly Patients

Presenter: Pantaleo Romanelli, M.D. (Renaissance Institute of Stereotactic Radiosurgery and Precision Oncology, Winter Park, Florida , USA)

4:15 PM

Phased Relief: Optimizing Dose for Bilateral Trigeminal Neuralgia Radiosurgery

Presenter: Shankar Vangipuram, M.D., DNB (Apollo Cancer Institute, Chennai, India)

4:25 PM

Neuroanatomical Synergy in Cyberknife Stereotactic Ablative Neuromodulation: Revisiting Contouring Paradigms with Dopamine PET-CT and Fgatir MRI for Ventral Intermediate Nucleus Targeting in Parkinson’s Disease for Improved Outcomes

Presenter: G. Lohith, M.D. (Immuno-Rad Lab, HCG Hospitals, Bangalore, India)

4:35 PM

Hypofractionated radiosurgery for functioning and non-functioning pituitary adenomas after surgery: Our working experience with Cyberknife unit.

Presenter: Eva Fernández Lizarbe, M.D. (Radiation Oncology, Ramón y Cajal University Hospital, Madrid, Spain)

4:45 PM

Single center clinical experience with Cyberknife radiosurgery for skull base meningiomas

Presenter: Eva Fernández Lizarbe, M.D. (Radiation Oncology, Ramón y Cajal University Hospital, Madrid, Spain)

4:55 PM

Long-Term Outcomes of Vestibular Schwannoma Treated with Stereotactic Radiosurgery: A Retrospective Study from a Single Institution

Presenter: David J. Park, MD, Ph.D., FCNS (Stanford University School of Medicine · Palo alto, USA)

5:05 PM

Multi-sequential stereotactic radiosurgery (SRS) for brain metastases: 10-year experience from the CHUV (Lausanne, Switzerland) brain metastasis clinic.

Presenter: Luis Schiappacasse, M.D. (CHUV, Lausanne, Switzerland)

5:15 PM

Treatment of glomus tumor with CyberKnife.

Presenter: Zeno Perini (San Bortolo Hospital, Vicenza, Italy)

Day 2: CNS Indications

Chaired by Dr Pantaleo Romanelli, M.D., Renaissance Institute of Precision Oncology & Radiosurgery, Winter Park, Florida, USA

Accuray Exchange President welcome and chair introduction

Presenter: Sean Collins (Tampa General Hospital, USA)

Chair welcome

Presenter: Pantaleo Romanelli (Renaissance Institute of Precision Oncology & Radiosurgery, USA)

Stereotactic diffusion tensor imaging tractography for brain AVM located in the in deep seated eloquent areas during radiosurgery treatment planning

Presenter: Enmin Wang (Huashan, China)

A proof of concept for MR-only workflow in CyberKnife intracranial radiosurgery

Presenter: Evaggelos Pantelis (National and Kapodistrian University of Athens, Greece)

Stereotactic radiosurgery in choroidal hemangioma with CyberKnife

Presenter: Kaan Oysul (Ankara, Turkey)

Simultaneous Multiple Brain Metastases SRS/SRT: An Evaluation of Dose Coverage Uncertainty Induced By Intra-Fraction Patient Motion during Beam Delivery

Presenter: Xiaoming Chen (Fox Chase, USA)

Multicenter approach to guide plan optimization of robotic intracranial SRS/SRT

Presenter: Sara Broggi (San Raffaele, Italy)

Retreatment for Resistant or Recurrent Pain in Trigeminal Neuralgia Using Frameless LINAC Radiosurgery

Presenter: Pantaleo Romanelli (Milan, Italy)

Clinical outcome and dosimetric feasibility of hippocampal sparing whole brain radiotherapy

Presenter: Bhuvana J. (Ahmedabad, India)

Day 3: Breast and Gynecological Cancers

Chaired by Barbara Jereczek-Fossa, M.D., Ph.D., University of Milan & European Institute of Oncology, Milan, Italy

Chief Medical Officer welcome and chair introduction

Presenter: Seth Blacksburg (Accuray)

Chair welcome

Presenter: Barbara Jereczek-Fossa (University of Milan & European Institute of Oncology, Italy)

Research on Thread Effect in HT Radiotherapy for Cervical Cancer

Presenter: Li Guang (Chongqing University Cancer Hospital, China)

Outcomes of pelvic reirradiation with stereotactic radiotherapy for gynaecological cancer recurrence

Presenter: Susan Lalondrelle (The Royal Marsden NHS Foundation Trust, UK)

CYBERNEO trial: Update of results at 14 years of follow-up

Presenter: Syrine Ben Dhia (Antoine Lacassagne Center, France)

Moderate hypofractionation with simultaneous integrated boost after conservative surgery for Bca

Presenter: Roberta Tummineri (San Raffaele, Italy)

Stereotactic Partial Breast Irradiation: 4-year Clinical Results and Cosmetic Outcomes

Presenter: Norbert Meszaros (National Institute of Oncology, Hungary)

Surface guided ring gantry radiotherapy in deep inspiration breath hold for breast cancer patients

Presenter: Mustafa Kadhim (Skåne University Hospital, Sweden)

Left breast cancer dosimetry with Accuray VOLO Ultra optimizer: a comparison with DIBH

Presenter: Patrizia Urso (Gruppo Ospedaliero Moncucco, Italy)

Preoperative single-fraction RT for early stage BC: preliminary results from CRYSTAL phase I/II study

Presenter: Maria Zerella (IEO, Italy)

Day 4: Thorax and Rare Indications

Chaired by Umberto Ricardi, M.D., University of Turin, Italy

Accuray Exchange Executive Board welcome and chair introduction

Presenter: Jun Yang, Ph.D.., JunXin Oncology Group, Foshan, Guangdong, China

Chair welcome

Presenter: Umberto Ricardi, University of Turin, Italy

Efficacy and Toxicity of Moderately Hypofractionated Radiotherapy Via Helical TomoTherapy Versus Conventional Radiotherapy Combined with Concurrent Chemotherapy for Patients with Unresectable Stage III Non-small Cell Lung Cancer: A Multicenter, Randomized Phase III Trial

Presenter: XiaoHong Xu (Zhongshan Hospital, China)

Optimization of Treatment Plan Parameters Used in Helical TomoTherapy for Small Cell Lung Cancer Patients with Extensive Pleural Metastasis

Presenter: Longyan Duan (Shanghai, China)

Radiation-Related Late Toxicities Following Total Marrow Irradiation Transplant Conditioning Regimens

Presenter: Colton Ladbury (City of Hope, USA)

Clinical outcomes following stereotactic ablative body radiotherapy to central lung tumours

Presenter: Julie Duong (Mount Vernon Cancer Centre, UK)

Modern radiotherapy for extended cutaneous lesions from lymphomas: results from a multicenter study

Presenter: Mario Levis (University of Torino, Italy)

Phase II Trial of TMLI 20 Gy in Combination with Cyclophosphamide and Etoposide in Patients with Poor-Risk Acute Leukemia

Presenter: Jeffrey Wong (City of Hope, USA)

Day 5: Genitourinary and Gastrointestinal Cancers

Chaired by Alison Tree, MBBS, BSc, FRCR, M.D.(Res), Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London, UK

Chief Medical Officer welcome and chair introduction

Presenter: Seth Blacksburg (Accuray)

Chair welcome

Presenter: Alison Tree (The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London, UK)

5-Year Outcomes from PACE B: An International Phase III Randomized Controlled Trial Comparing Stereotactic Body Radiotherapy (SBRT) vs. Conventionally Fractionated or Moderately Hypo Fractionated External Beam Radiotherapy for Localized Prostate Cancer

Presenter: Nick van As (The Royal Marsden NHS Foundation Trust, UK)

The UPRATE trial: feasibility of seminal vesicle PTV-margin reduction with online adaptive SBRT

Presenter: Victor Brand (Erasmus, Netherlands)

SBRT Focal Boost for Localised Prostate Cancer: Primary Outcomes of the SPARC Prospective Trial

Presenter: Binnaz Yasar (The Royal Marsden NHS Foundation Trust, UK)

Early PSA Kinetics in Patients Treated with Prostate SBRT with Intra-Prostatic Boost

Presenter: Nima Aghdam (Beth Israel, USA)

Outcomes of a phase II trial of high-dose online-adaptive SBRT for abdominal oligometastases

Presenter: Lucy A. van Werkhoven (Erasmus, Netherlands)

SBRT and systemic therapy for patients with Oligometastatic Renal Cell Carcinoma

Presenter: Miriam Torrisi (Ospedale San Raffaele, Italy)

SABR for Liver De Novo, Repeat, and Induced Oligometastatic Disease

Presenter: Miriam Torrisi (Ospedale San Raffaele, Italy)

Acute toxicity from PACE-C comparing Stereotactic Body Radiotherapy (SBRT) with moderate hypofractionation (MHRT)

Presenter: Alison Tree (The Royal Marsden NHS Foundation Trust, UK)

100 - Primary Outcome Analysis for Shortening Adjuvant Photon Irradiation to Reduce Edema (SAPHIRE): A Randomized, Phase III Trial of Hypo- vs. Conventionally Fractionated Regional Nodal Irradiation (RNI)

Monday, February 3rd, 2025

8:00 AM – 8:10 AM ET

Location: Room 202

Presenter(s)

Name of Presenter

Name of Institution
City, State

K. E. Hoffman¹, S. F. Shaitelman¹, W. Qiao², R. Z. Zacharia³, I. Y. Arzu⁴, E. Bloom¹, C. R. Goodman¹, M. M. Joyner¹, L. L. Mayo⁵, M. P. Mitchell¹, G. H. Perkins⁴, J. Reddy³, P. Singh⁶, M. C. Stauder¹, E. A. Strom¹, V. K. Reed¹, P. J. Schlembach³, W. Tereffe⁴, W. A. Woodward¹, and B. D. Smith¹; ¹Department of Breast Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ²Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, ³Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁴The University of Texas MD Anderson Cancer Center, Houston, TX, ⁵Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁶Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Purpose/Objective(s): Although RNI improves breast cancer survival, it increases risk of upper extremity lymphedema. We hypothesized that hypofractionated RNI may reduce lymphedema risk.

Methods: Patients with a recommendation for RNI for cT0-T3, N0-N2a, N3a invasive breast cancer were randomized between standard RNI (STD-RNI: 50 Gy to breast/chest wall and 45 Gy to RN) or shorter RNI (SH-RNI: 40.05 Gy to breast/chest wall and 37.5 Gy to RN). Patients were stratified by receipt of chemotherapy, body mass index (BMI), type of axillary surgery, and difference in arm volume prior to RNI. RN targets included the internal mammary, infraclavicular, and supraclavicular nodal basins; the level I and II axilla was treated if axillary lymph node dissection was not performed. Boost to the tumor bed or chest wall was permitted. Lymphedema was assessed via standard toxicity grading by the treating physician and by serial perometry measurement prior to surgery, post-operatively and then 6, 12, 18, and 24 months after radiation. The primary outcome was defined as a =10% relative difference in arm volume on at least one post-radiation perometry assessment, normalized by the pre-operative perometry measurement. Secondary outcomes included comparison of physician-reported toxicities using the NCI CTCAE v4.0 scale graded weekly during RT, at 6 months, and then annually. Fisher’s exact tests compared groups. Local-regional recurrence (LRR) was calculated using the Kaplan-Meier method and compared using the log-rank test.

Results: 324 patients across 5 treatment centers were enrolled and randomized from 2017 to 2022 with median follow up of 4.75 years. Clinical-pathologic covariates were well-balanced by treatment arm. Median age was 54 years, 64% were Non-Hispanic White, and 39% had BMI >30. 57% underwent mastectomy with or without reconstruction and 42% underwent segmental mastectomy. 68% underwent axillary lymph node dissection and 90% received chemotherapy. Perometry-assessed lymphedema, the primary outcome, was less common after SH-RNI (29%) than STD-RNI (36%), but the difference was not statistically significant (p=0.24). In contrast, physician-assessed lymphedema was significantly less common with SH-RNI than STD-RNI (15% vs. 27%, p=0.009). Patients randomized to SH-RNI were less likely to experience any grade =2 toxicity (52% vs. 78%, p<0.001). Pneumonitis was uncommon and similar between groups (3% vs 2%, p=0.46). There were no brachial plexopathy events. Five-year LRR risk was 3% with SH-RNI and 2% with STD-RNI (P=0.48).

Conclusion: In this primary outcome analysis of a multisite phase III randomized clinical trial, SH-RNI did not lower risk of perometry-assessed lymphedema. However, SH-RNI conferred a low risk of LRR and reduced the risk of physician-reported lymphedema and grade 2 or higher toxicity when compared to STD-RNI.

Frameless Radiosurgery Is a Safe and Effective Treatment for Medically-Refractory Trigeminal Neuralgia in Elderly Patients

Presenter

Pantaleo Romanelli, M.D.

Renaissance Institute of Stereotactic Radiosurgery and Precision Oncology
Winter Park, Florida , USA

Pantaleo Romanelli¹, Giancarlo Beltramo², Evan Thomas³, Alfredo Conti⁴

1. Neurosurgery, Renaissance Institute of Stereotactic Radiosurgery and Precision Oncology, Winter Park, Florida , USA 2. Radiation Oncology, CDI, Milano, ITA 3. Radiation Oncology, Ohio State University, Columbus, USA, 4. Neurosurgery, University of Bologna, Bologna, ITA

Objectives:

Trigeminal Neuralgia (TN) is a devastating pain disorder often affecting elderly patients. Medical therapy failure is common, either due to drug intolerance or refractoriness. Surgical treatment options in very old patients can be restricted by a variety of health issues. Frameless radiosurgery provides the least invasive treatment today available for TN. Radiosurgery is a widely proven treatment for TN with an exceedingly rare complication rate (aside from sensory dysfunction). This paper aims to investigate the safety and efficacy of frameless radiosurgery for TN in the elderly population.

Methods:

A cohort of 503 TN patients treated with frameless Cyberknife radiosurgery from 2013 to 2023 was retrospectively analyzed to extract outcome data regarding patients older than 80 years. Pain intensity was assessed using the Barrow Neurological Institute Pain Scale (BNI-PS) and the Visual Analogue Score (VAS). Facial numbness was evaluated using the BNI Numbness Scale (BNI-NS). Pre- and post-treatment scores have been assessed, respectively, immediately before undergoing treatment and 3,6,9 and 12 months after. The post-treatment scores after 12 months are reported. Treatment protocol has been previously described: in short, a 6 mm segment of the nerve in retrogasserian/midcisternal location typically receives a prescribed dose of 60 Gy. Prescription isodose is usually set at the 80%. Maximum dose does not exceed 75 Gy. Treatment volume is typically around 30 mm³. In case of retreatment due to failure of the first treatment or relapse, the dose typically prescribed is 40 Gy. Treatment is tailored to patient anatomy, so that length of the nerve treated, prescribed dose and prescription isodose, maximum dose and treatment volume may change substantially from case to case.

Results:

This cohort of 503 patients included 298 patients younger than 70-year-old (59%) and 205 patients older than 70 (41%). Patients older than 70 included 134 patients aged 70-79 (27%), 62 patients aged 80-89 (12%) and 9 patients aged 90-100 (2%). Clinical outcomes of 71 patients aged 80 to 100 years (14 % of the entire cohort, median age 83 y) are reported. The median age of the 90–100-year-old group was 92 y. The median age of the 80–89-year-old group was 82 y. The median prescribed dose in both groups was 60 Gy (range 40-65 Gy). 5 patients out of 71(7%) underwent retreatment after previous CK radiosurgery receiving 45 Gy (2) or 40 Gy (3), all achieved stable pain control.
BNI-PS pre-treatment score was V in 39 patients, IV in 25, III in 7, II and I in 0. No patients had post-treatment BNI-PS scores of V and IV. Scores of III, II, and I have been found, respectively, in 9, 27 and 35 patients.

Pre-treatment VAS score was 7-10 in 64 patients, 4-6 in 7 and < 4 in 0. Post-treatment VAS score was 7-10 in 0, 4-6 in 12 and < 4 in 59.

BNI-NS pre-treatment score was one in 62 patients, II in 9, III and IV in 0. BNI-NS post-treatment score was one in 54, 15 in 9, III in 2 and IV in 0.

In summary, pain disappeared or improved in respectively 59 (83%) and 5 (7%) patients while only 2 out of 71 (3%) developed hypoesthesia associated with bothering paresthesias (grade III BNI-NS).

Conclusion:

Frameless radiosurgery provides excellent outcomes in the treatment of TN in the elderly population. No major medical or neurological complications were found. Pain improved or disappeared in 90% of the patients while only 3% developed bothering paresthesias. These data not only show remarkable efficacy and safety of frameless TN radiosurgery in the elderly population but also support the notion that radiosurgery should be considered as the elective treatment for elderly patients with medically refractory TN. Further study is needed.

Phased Relief: Optimizing Dose for Bilateral Trigeminal Neuralgia Radiosurgery

Presenter

Shankar Vangipuram, M.D., DNB

Apollo Cancer Institute, Chennai, India

V. Shankar1, D. Arjundas2, S. Ghosh3, G. Laksmipathy4, S. Meenakshi Sundaram5, S. Cholayil1, V. L. Arulselvan6, S. Muthukani7, V. R. Anand8, K. Bhanu9, and V. Sai Shreya10

¹Apollo Cancer Centers, Chennai, India, ²Chief Neurologist, Mercury Hospital, Chennai, India, ³Dept. of Neurosurgery, Apollo Proton Cancer Center, Chennai, India, ⁴Dept. of Neurology, Apollo Hospitals, Greams Unit, Chennai, India, ⁵Apollo Hospitals, Madurai, India, ⁶Dept.of Neurology, Apollo Hospitals, Greams Unit, Chennai, India, ⁷Dept. of Neurology, Apollo Hospitals, Greams Road, Chennai, India, ⁸Sai Neuro Hospital, Chennai, India, ⁹Mehtas Hospital,, Chennai, India, ¹⁰ACSR Govt. Medical College, Nellore, India

Purpose/Objective(s):

Bilateral trigeminal neuralgia (BTN), a rare condition that poses a unique therapeutic challenge as aggressive interventions risk bilateral complications which impair QOL like facial numbness and corneal anesthesia, This study aims to evaluate the efficacy and safety of staged radiosurgery (SRS) for BTN, with a focus on adaptive dosing strategies to balance pain control and toxicity reduction.

Materials/Methods:

A retrospective cohort analysis (between 2010-2023) was conducted on 12 patients with medically refractory BTN treated using a frameless robotic radiosurgery. Patients were stratified into two cohorts: idiopathic TN (n=7) and MS-associated TN (n=5). Treatment was delivered in two stages, separated by a minimum 6-month interval to allow toxicity assessment from the first procedure. The initial SRS targeted the trigeminal nerve root entry zone (REZ) at a median dose of 85 Gy (range: 80–90 Gy) prescribed to the 50% isodose line. For the second-side treatment, doses were adapted based on post-first-SRS toxicity: patients with minimal facial numbness (BNI grade =III) received 80 Gy (n=4), while those with significant numbness (BNI grade IV) received reduced doses of 70–75 Gy (n=8). Outcomes were assessed using BNI pain intensity scale and facial numbness scale. Toxicity included bothersome numbness (BNI IV) or severe complications (e.g., anesthesia dolorosa). Non-parametric statistical analyses were employed due to small sample size, with significance set at p<0.05.

Results:

Initial pain relief (BNI I–IIIb) was achieved in 71.4% (10/14) after the first RS and 57.1% (8/14) after the second. At 2 years, 57.1% (8/14) maintained adequate control (BNI I–IIIa). Recurrence occurred in 42.9% (6/14), with a median time to recurrence of 14 months (first-treated side) and 18 months (second-treated side). Patients with MS had lower success rates (40% vs. 66.7% in idiopathic TN; p=0.29) and earlier recurrence (median: 11 vs. 16 months). Facial numbness (BNI IV) developed in 21.4% (3/14) after the first RS and 28.6% (4/14) after the second; one patient (7.1%) experienced bilateral mild numbness. No severe complications (e.g., anesthesia dolorosa, motor deficits) occurred. Higher radiation doses (=80 Gy) correlated with better pain control (p=0.04) but increased numbness risk (p=0.07).

Conclusion:

Staged radiosurgery, with a minimum time interval of 6mo, provides effective pain relief for BTN, with careful dose adaptation playing a critical role in mitigating bilateral toxicity. Reducing the second-side dose to 70–75 Gy in patients with first-side numbness significantly lowers the risk of facial sensory complications without compromising pain control. Patients with MS exhibit lower response rates, necessitating further investigation into alternative strategies. These findings highlight the importance of individualized dosing to optimize therapeutic outcomes in BTN, though larger studies are needed to refine dosing and timing protocols.

Neuroanatomical Synergy in Cyberknife Stereotactic Ablative Neuromodulation: Revisiting Contouring Paradigms with Dopamine PET-CT and Fgatir MRI for Ventral Intermediate Nucleus Targeting in Parkinson's Disease for Improved Outcomes

Presenter

G. Lohith, M.D.

Immuno-Rad Lab, HCG Hospitals, Bangalore, India

G. Lohith¹, K. Sekar², S. S. Shivalingappa³, K. Kallur³, A. K. BS³, A. Pichandi⁴, and H. G. ramesh Gowda⁵

¹Immuno-Rad Lab, HCG Hospitals, BANGALORE, India, ²HCG Hospitals, Bengaluru, karnataka, India, ³Health Care Global Enterprises Ltd, Bangalore, India, ⁴HCG Hospital, Banglore, India, ⁵HCG Hospitals, Bengaluru, Karnataka, India

Purpose/Objective(s):

A frameless robotic radiosurgery system is a non-invasive approach for alleviating motor symptoms in Parkinson’s disease (PD) by targeting dysfunctional neural circuits, such as the ventral intermediate nucleus (ViM), subthalamic nucleus or globus pallidus. This system delivers highly focused radiation for precise neuromodulation. Advanced imaging, including dopamine PET-CT and fast gray matter T1-weighted MRI, enhances treatment precision. Dopamine PET-CT maps dopamine deficiency, a hallmark of PD, while fast gray matter T1 MRI improves structural visualization for accurate ViM localization. Fusing these modalities ensures precise targeting while minimal damage to healthy tissue and improving outcomes.

Materials/Methods:

9 Indian patients with tremor-predominant PD underwent CR ViM targeting using dopamine PET-CT and FGATIR MRI. The mid-commissural line served as reference, with a target 12 mm lateral to this line. A 3 mm volume was contoured above the target across three MRI slices for lesioning precision. The ViM’s horizontal extent ranged from 9 to 11 mm, necessitating individualized adjustments. Instead of relying solely on fixed measurements, we used the internal capsule as lateral endpoint, verified with FGATIR MRI. Dopamine PET-CT also aided in lateralizing the side of dopaminergic deficiency, enhancing targeting accuracy. CR provided frameless, stereotactic Vim ablation using 85Gray single fraction keeping internal capsule max dose < 35 Gray for optimal tremor control.

Results:

90% of patients experienced more than 80% tremor relief, while remaining 10% saw over 50% improvement. The multimodal imaging approach significantly enhanced Vim localization, optimizing stereotactic interventions. Internal capsule-based lateral boundary assessment improved tremor control outcomes, reducing inaccuracies seen with conventional techniques. A frameless robotic radiosurgery system proved to be non-invasive, effective alternative to traditional interventions, achieving durable tremor suppression. Statistical analysis confirms that a frameless robotic radiosurgery system significantly improves tremor severity, validating its efficacy for treating tremor-predominant Parkinson’s disease.

Conclusion:

Integrating PET-CT and FGATIR MRI enables precise ViM localization, particularly in Indian patients with anatomical variations. Using the internal capsule as a lateral boundary improves stereotactic accuracy, minimizing reliance on predefined measurements. Dopamine PET-CT further aids in lateralizing dopaminergic deficiency, supporting patient selection and intervention planning. A frameless robotic radiosurgery system offers a precise and effective non-invasive treatment option, reducing risks associated with invasive procedures

Statistic	Value
Sample Size (n)	9
Mean Pre-Treatment Grade	3.89
Mean Post-Treatment Grade	1.11
Mean Difference (Pre – Post)	2.78
Standard Deviation of Differences	0.83
t-Statistic	10.00
p-Value	8.49 × 10?6

Hypofractionated radiosurgery for functioning and non-functioning pituitary adenomas after surgery: Our working experience with Cyberknife unit.

Presenter

Eva Fernández Lizarbe, M.D.

Radiation Oncology, Ramón y Cajal University Hospital, Madrid, Spain

Julen Azcona Martin1, Marta Camacho Manzanares1, Eva Fernández Lizarbe1, Ignacio Maria Gómez Paloma1, Mercedes Martín Sánchez1, David Sevillano Martínez2, Juan David García Fuentes2, Adrian Durango1, María Dolores Espinosa1, Isabel Alvira1, Margarita Martín2, Patricia Martín Nieto1, Marina Alarza Cano1, Rubén Chillida Rey2, Sonsoles Sancho García1

1 2 Radiation Oncology, Ramón y Cajal University Hospital, Madrid, Spain. Radiophysicis, Ramón y Cajal University Hospital, Madrid, Spain

Purpose/Objective:

The aim of this report is to evaluate and present the clinical outcomes and tolerance profile of hypofractionated radiosurgery for both functioning and non-functioning pituitary adenomas after partial resection. The original single fraction radiosurgery has been limited to those cases presenting small and far from the organs at risk lesions. Using the new intrafraction image guided and frameless technologies, as the Robotic Radiosurgery Unit Cyberknife, we are now allowed to deliver radiosurgery in 3-5 fractions for more complex cases.

Material/Methods:

Between June 2020 and June 2024, a total of 30 patients (13 women and 17 men) with a median age of 48,5 years were treated post-surgically with radiotherapy in our center. 27 patients presented macroadenomas and only 3 microadenomas; 13 were intrasellar (43,3%), 14 presented cavernous sinus invasion (46,7%) and 3 extrasellar (10%).

7 of them were functioning adenomas (2 ACTH-secreting, 2 prolactinoma and 3 GH-secreting). Radiotherapy indications after surgery were either remanent tumor growing, biochemical failure or poor systemic treatment tolerance

A non-contrasted CT scan and a magnetic resonance (MRI) with T1, T2 and T1 with contrast and fat suppressing sequences were used in every patient for treatment planning.

Results:

The most commonly used fractionations were 24 Gy in 3 fractions and 25 Gy in 5 fractions; both used in 9 cases. For the 24 Gy in 3 fr we reached median max doses of 33,61 Gy in hypophysis, 13,8 Gy in optic chiasm; 8 Gy left optic nerve and 10 Gy in right optic nerve. Whereas for the 25 Gy in 5 fractions median max doses were 34,15Gy in hypophysis, 22,79 Gy in optic chiasm; 9,73 Gy left optic nerve and 24 Gy in right optic nerve. The median follow-up was 26 months (7-47 months). We have observed that 40% of the adenomas have decreased in size, and the rest have remained stable without any growth. Two out of six functioning patients have achieved biochemical control.

The tolerance of the treatment was excellent. Only in 10 patients (43,5%) acute toxicity was reported consisting of grade 1-2 transient cephalea. Not chronic toxicity was reported except for a single case of transient diplopia with no visual acuity lost, completely recovered after steroids.

Conclusion:

Hypofractionated radiosurgery for pituitary adenomas appears to be a feasible and safe option for patients with large volumes or sinus involvement. In our series, we report radiological responses or stability for all treated patients with acceptable acute toxicity.

Single center clinical experience with Cyberknife radiosurgery for skull base meningiomas

Presenter

Eva Fernández Lizarbe, M.D.

Radiation Oncology, Ramón y Cajal University Hospital, Madrid, Spain

Mercedes MARTÍN SANCHEZ , Fernández Lizarbe EVA, Martín Martin MARGARITA, Sevillano DAVID, Garcia JUAN DAVID, Alba Perez BEATRIZ, Quintana JUAN VICENTE, Medina Diaz MONTSERRAT, Garcia FELICIANO, Sancho Garcia SONSOLES

Hospital Universitario Ramón y Cajal, Madrid, Spain

Objectives:

The aim of this retrospective study is to evaluate the efficacy in local control and tolerance of radiosurgery (single RS or hypofractionated HRS doses) for the treatment of skull base meningiomas

Material and methods:

We analysed the treatment of 30 patients diagnosed with skull base meningiomas treated with CyberKnife Radiosurgery between March 2020 and February 2024. Planning was performed using CT-plan with termoplastic inmobilization mask registered with brain nuclear magnetic resonance using T1-weighted MRI with contrast and fat saturation (useful in skull base tumors, orbital lesions, or surgical beds) and high-resolution T2-weighted MRI (useful in cisternal segments of cranial nerves, cavernous sinuses or Meckel’s cave). All contours are reviewed by a dedicated neuroradiologist. In resected or unresected grade 1 meningiomas, the GTV = PTV. In grade 2 meningiomas, a margin of 1-5 mm was applied, according to international contouring guidelines.

Results:

Out of 30 patients, 22 women and 8 men. Mean age 62 years old (39-87). Most common locations were: pontocerebellar angle (14p), cavernous sinus (6p), optic nerve (4p) and others (6p). 13 patients had undergone previous surgery. 83% (25p) received a total dose of 25-30Gy in 5 fractions, 17% (5p) single fraction (14-18Gy). Mean lesion volume 10cc .For the 5 fractions scheme: mean maximum dose (Dmax) in PTV was 46.04 Gy,, mean Dmax in visual pathway 30.67Gy, pituitary 36.69Gy and brainstem 30.50Gy. For 1 fraction scheme: mean Dmax in PTV was 20.96 Gy, mean Dmax in visual pathway 7.46Gy, pituitary 7.97 Gy and brainstem 9.84 Gy.Mean conformation index of 1.3.With a median follow-up of 24 months (3-59) for 26 p who underwent the first control RMI, 100% patients achieved radiological stability. Acute toxicity was reported in 46% of patients presenting minor grade 2 toxicity, most frequently mild transient headache and asthenia. Chronic toxicity was evaluated for 26p, 26% presented minor grade 2 headache (6), neurological deterioration (1) and tinnitus (1). No cases of stroke or cranial nerve palsy were reported. Radiologic radionecrosis occurred in 1 asymptomatic patient.

Conclusions:

Our clinical experience using Cyberknife RS or HRS for skull-base meningiomas shows that these schemes are safe, effective, and helpful for patients who are rarely candidates for complete resection.

Long-Term Outcomes of Vestibular Schwannoma Treated with Stereotactic Radiosurgery: A Retrospective Study from a Single Institution

Presenter

David J. Park, MD, Ph.D., FCNS

Stanford University School of Medicine · Palo alto, USA

David J. Park1, Ahed H. Kattaa1, Juan J. Cardona1, Elaheh Shaghaghian1, Amirhossein Akhavan-Sigari1, Shagun Ravi Nasta1, Harini Voruganti1, Isabelle Lee1, Yusuke S. Hori1, Sara Emrich1, Louisa Ustrzynski1, Armine Tayag1, John R. Adler1, Steven D. Chang1

1 Neurosurgery, Stanford University School of Medicine, Palo alto, USA

Objectives:

Vestibular schwannoma (VS) is a benign tumor arising from cranial nerve VIII, commonly affecting the internal auditory canal and the cerebellopontine angle. This study evaluates the long-term efficacy and safety of stereotactic radiosurgery (SRS) using CyberKnife, a platform pioneered at Stanford, highlighting our institution’s extensive long-term experience and data.

Methods:

We retrospectively analyzed a total of 344 VS cases treated with CyberKnife SRS from 1998 to 2014. Data included patient demographics, clinicopathology, radiology, and treatment details. Statistical analyses included Chi-square tests, Mann-Whitney U tests, independent t-tests, and Kaplan-Meier analysis.

Results:

The median follow-up was 157 months, representing one of the longest follow-up periods reported. The mean age was 51.9 years, with 50.9% female patients. The median tumor size was 1.7 cm, with a median target volume of 0.94 cc. Median maximum and prescribed doses were 22.5 Gy and 18 Gy, respectively. NF2 patients received higher doses (P=0.016) and had longer follow-up (P=0.012). NF2-associated tumors more frequently presented with higher Koos grades and required additional interventions (P=0.025). CN V deficits correlated with CN VIII symptom resolution (P=0.002). Notably, smokers (P=0.001) and non-hypertensive patients (P=0.001) had higher symptom resolution rates. Local recurrence was higher in those with prior surgery (P=0.048). Remarkably, local control rates were 100% at 2 years, 98.8% at 5 years, 94.2% at 15 years, and 89.3% at 25 years. Overall survival was 100% at 10 years and remained at 97.1% at 25 years.

Conclusion(s):

Our extensive long-term data confirm that CyberKnife SRS provides sustained local control and safety for VS treatment over decades, reinforcing its role as a reliable and effective management strategy pioneered at Stanford.

Treatment of glomus tumor with CyberKnife.

Presenter

Zeno Perini

San Bortolo Hospital, Vicenza, Italy

Zeno Perini

San Bortolo Hospital, Vicenza, Italy

Introduction:

Glomus tumors, also known as paragangliomas, are benign, slow growing tumors, originating from neuroectodermal tissues. They are highly vascular lesions and arise from the capillary and precapillary blood vessels, located along the tympanic branch of glossopharyngeal nerve (Jacobson’s nerve). It occurs predominantly in women and are typically diagnosed between the fifth and sixth decade of life. Clinical aspects present as pulsatile tinnitus followed by conductive hearing loss, otalgia, and aural fullness.

Materials and Methods:

From January 2003 to December 2023, 51 patients (42 females and 10 males) affected by tympanojugular glomangioma were treated with CyberKnife at our Center. The age ranged from 32 to 85 years (m: 59.7, M: 62). The average lesion volume treated was 4457 mm3 (median: 2660 mm3) while the range: 91-29331 mm3. Four patients showed multicentric lesions. Six patients underwent 2 treatments and three underwent 3 treatments. While the maximum treatment doses delivered were between 16 and 27.5 Gy (average 21.3 Gy). The isodoses are between 75-80%. In particular, a maximum dose of 22.5 Gy was used on 18 patients (34%). As regards fractionation, the majority of patients, 34/51, underwent three fractions while 6 underwent a single session. No re-treatment was performed less than three years after the previous one. The FU has a range of 5-150 months for a total of 2796 months of observation (average: 65). 43 patients underwent FU, 7 patients did not show up for checks while one died from senectus. Radiological FU was scheduled at 6-12-18-24-30 and 36 months after treatment; 38 patients underwent checks with thin-layer contrast-enhanced MRI while the other 5 underwent high-definition contrast-enhanced CT due to no indication for MRI.

Results:

In 43 patients observed, 6 (14%) presented initial disease progression (PD). However, only one actually showed full-blown disease progression while five were re-treated. 27 patients (63%) experienced disease stabilization with a single treatment (SD) while 8/43 patients (23%) experienced disease dimensional regression (RD), 2 of which after retreatment. As regards the clinical aspect, 19 patients showed a clear regression of the initial symptoms; 8 showed new symptoms (not serious and/or debilitating) while 2 underwent progression (hearing loss and tinnitus). The remainder remained neurologically quo-ante.

Safety and efficacy of CyberKnife radiosurgery plus Anlotinib hydrochloride in patients with recurrent glioblastoma: a prospective phase II single-arm study (HSCK-002)

Presenter

Yun Guan

Huashan Hospital, China

Yun Guan, Wei Zou, Li Pan, Enmin Wang, Yang Wang, Xin Wang

Shanghai, China

Background: Glioblastoma (GBM) is a tumor known for its highly vascular nature and limited treatment options upon disease recurrence. While Bevacizumab which target VEGF-A has gained approval for treating recurrent glioblastoma (rGBM), the multi-target tyrosine kinase inhibitor Anlotinib has the ability to directly target Vascular Endothelial Growth Factor Receptor (VEGFR), Platelet-Derived Growth Factor Receptor (PDGFR), and Fibroblast Growth Factor Receptor (FGFR). Theoretically, its anti-angiogenic effect may exceed that of Bevacizumab, and preliminary studies have shown its therapeutic efficacy in rGBM, indicating promising treatment potential. This study aims to present findings regarding the effectiveness and safety of combining Anlotinib with stereotactic radiosurgery (SRS) in treating patients with rGBM.

Methods: HSCK-002 is a prospective single-arm, single center, phase II study (ClinicalTrials.gov Identifier: NCT04197492). Patients who underwent surgery, standard radiotherapy, and temozolomide chemotherapy and were diagnosed with recurrence based on Response Assessment in Neuro-Oncology (RANO) criteria and/or biopsy were eligible for inclusion. Each patient underwent CyberKnife SRS (25Gy/5fx) in combination with oral administration of Anlotinib (12 mg, daily, days 1–14/3 weeks) until encountering disease progression or experiencing intolerable adverse effects. The primary objective was the investigator-assessed median overall survival (OS) using the RANO criteria.

Results:

Between December 2019 and July 2023, 22 patients (median age: 55 years; range: 28–70 years) were included. According to RANO criteria, 21 patients exhibited tumor response, with 6 achieving complete response, resulting in an objective response rate of 95.5%. Additionally, one patient maintained stable disease without progression. Median progression-free survival (PFS) was 9.1 months (95% CI, 7.5–24.7), with a 6-month PFS rate of 85.7% (95% CI, 71.9–100.0). Median overall survival was 19.5 months (95% CI, 10.6–46.8). Common adverse events included hand-foot skin reactions (40.9%), hypercholesterolemia (27.3%), and hypertension (22.7%). Four patients experienced grade 3 adverse events, accounting for an 18.2% incidence rate. Therapy discontinuation due to ischemic stroke (grade 3) occurred in one patient. No grade 4 events or treatment-related deaths were reported.

Conclusions: The combination of salvage SRS with Anlotinib demonstrated promising outcomes and manageable toxicity in managing recurrent GBM. Currently, a phase II randomized controlled trial, supported by the Shanghai Municipal Commission of Health, is underway. This trial aims to compare the efficacy of Anlotinib combined with radiosurgery against Bevacizumab combined with radiosurgery for the treatment of rGBM patients, further exploring this therapeutic regimen.

Stereotactic diffusion tensor imaging tractography for brain AVM located in the in deep seated eloquent areas during radiosurgery treatment planning

Presenter

Enmin Wang

Huashan, China

Enmin WANG, Xiaoxia LIU, Xin WANG, Huaguang ZHU, Xing DI, Wenqian XU
Shanghai, China

Objective:

The integration of modern neuroimaging into treatment planning has increased the therapeutic potential and safety of stereotactic radiosurgery. The authors report their method of integrating stereotactic diffusion tensor imaging (DTI) tractography into treatment planning for CyberKnife radiosurgery (CKRS). The aim of this study was to evaluate whether the use of diffusion-tensor tractography (DTT) of the corticospinal tract could reduce motor complications after radiosurgery.

Methods:

Between 2013 and 2020, 56 patients with arteriovenous malformation (AVM) in the deep frontal lobe, deep parietal lobe, basal ganglia, and thalamus who had undergone CKRS. DTI were obtained on the day before the localization of head. Data from stereotactic 3D imaging studies were co-registered with the data from DTI tractography. The combined images were transferred to a Cyberknife treatment-planning workstation. During the procedure of creation of treatment planning, the corticospinal tract was clearly visualized on the Multiplan.

Results:

56 patients with AVM volume less than 10 cm3 underwent CKRS in Huashan Hosptial. The follow-up time ranged from 36 to 120 months, with median time of 78 months. The prescription dose was 21Gy-22 Gy in 2 fractions or 21Gy – 22.5 Gy in 3 fractions according to AVM volume. A maximum dose to the corticospinal tract of equal to or less than 21 Gy in 3 fractions or 18 Gy in 2 fractions did not cause new neurological deficits. Total obliteration rates were 72% at more than 3 years after one stage or two stage CKRS. One patient had small intracranial hemorrhage 3 years post obliteration. Mild complications were observed in 6 patients because of brain edema, which was required medication.

Conclusion:
Integration of stereotactic tractography into CKRS represents a promising tool for preventing radiosurgery complications by reduction in radiation doses to functional organs at risk, including critical cortical areas and subcortical white matter tracts. DTI improved the obliteration of AVM and reduced the motor deficits.

A proof of concept for MR-only workflow in CyberKnife intracranial radiosurgery

Presenter

Evaggelos Pantelis

National and Kapodistrian University of Athens, Greece

Evaggelos Pantelis1,2, Argyris moutsatsos2, Panagiotis Archodakis1,2, Sami Romdhani3, Anastasia Stergioula2, Panagiotis Papagiannis1, Nikos Paragios3

1National and Kapodistrian University of Athens, Medical Physics Lab, Medical School, Athens, Greece. 2Iatropolis Clinic, Radiotherapy department, Athens, Greece. 3TheraPanacea, R&D Artificial Intelligence, Paris, France

Purpose/Objective: CyberKnife® (Accuray Inc.) radiosurgery relies on CT images for precise dose calculations and generating digital reconstructed radiographs (DRRs) for kV x-ray based image-guided treatment delivery. To enhance the accuracy of target and organ at risk delineation, MR images are routinely acquired and co-registered with the treatment planning CT scan. However, this procedure introduces a registration uncertainty, which is propagated throughout the treatment. Implementing an MR-only workflow using synthetic CTs eliminates registration uncertainties, while optimizes patient comfort and the imaging resources necessitated for treatment planning. In this study, we implemented an MR only workflow for intracranial CyberKnife radiosurgery, utilizing artificial intelligence (AI) techniques to generate synthetic-CT (sCT) images from MRI scans. These sCTs were used for dose calculations and DRR generation.

Material/Methods: A complete set of planning CT along with co-registered T1w-MR images, DRRs and treatment plan details for ten acoustic neurinoma cases equally distributed to both sides of skull base, were exported from the CyberKnife database. SCTs were generated using a novel AI based model. This model was trained using an end-to-end ensemble approach, integrating self-supervised Generative Adversarial Networks (GANs) with focus on cycle consistency, leveraging both planning CTs and T1w-MRIs of the brain as references. The training dataset comprised a retrospective cohort featuring pairs of CT and co-registered MR images obtained from different hardware vendors. sCTs of 1 mm slice thickness, 512 x 512 reconstruction matrix and a 25.5 cm field of view (FOV) were generated from the co- registered patient T1w-MR scans and imported into the CyberKnife system for DRR generation. The sCT-based DRRs (sDDRs) were then exported and compared with the corresponding CT-based DRRs using the structure similarity index (SSIM) and Dice coefficient. Dosimetry was performed using a ray-tracing based dose calculation algorithm developed in-house that accounts for tissue heterogeneities using the effective path length of each voxel traced by the beam. For each case two dosimetry calculations were performed, using either the CT or the sCT, but the same treatment planning parameters (i.e., beam position and orientation, Monitor Unit per beam, etc). Dose results for each case were compared with respect to target coverage, the maximum brainstem dose and the mean dose to the ipsilateral cochlea.

Results: The sCTs and sDRRs displayed similar visualizations compared to their corresponding CT and DRR counterparts, although exhibiting decreased contrast (see Figure 1). The mean Dice coefficient and SSIM index between the DRRs and sDDRs were 0.96 ± 0.1% and 0.91 ± 0.4%, respectively. The mean difference in the target volume covered with the prescribed isodose surface was found equal to 4.3% ± 4.8%. Moreover, the mean difference in the maximum dose to the brainstem and mean dose to the ipsilateral cochlea were found equal to 3.4% ± 8.7% and 4.3% ± 4.8%, respectively. The observed differences could be attributed to the absence of imaging data in the oral cavity in the MRI images, and therefore in the sCTs, that is included in the CTs and DRRs, as well as to the reduced contrast of the sCTs affecting the effective path length calculations.

Conclusion: In this study, we have provided a compelling proof of concept that an AI-based approach to generate synthetic CTs offers a viable solution for an effective implementation in CyberKnife intracranial radiosurgery. AI based sCTs obviate the need for manual structure segmentation or acquisition of special MR sequences. However, prior to its clinical adoption, it is imperative that the MRI scanning protocol encompasses the entirety of the head & neck region, and further refinements should be made to the AI model to augment the contrast of the generated sCTs, thereby optimizing their utility in this critical medical application.

Stereotactic radiosurgery in choroidal hemangioma with CyberKnife

Presenter

Kaan Oysul

Ankara, Turkey

Kaan OYSUL, Murat TUNC, Hasan UYSAL, Mehmet Fazil ENKAVI, Sait SIRIN
Ankara, Turkey

Purpose: To analyze the clinical outcome of stereotactic radiosurgery (SRS) in a series of patients with choroidal hemangioma.

Methods: Twenty-two patients with circumscribed or diffuse choroidal hemangioma with visual deterioration and at least 12 months of follow-up were included in the study. Patients were treated with one fraction of SRS with Cyberknife. Clinical results were analyzed for tumour size, location, subretinal fluid, retinal detachment, visual acuity and visual improvement by Snellen lines. Parametric statistical tests were used for subgroup analysis.

Results: The mean age was 40 (10-78); 17 cases were male, and five were female. The mean follow-up was 22 months. Five cases (23%) had diffuse, and 17 (77%) had circumscribed angioma. Four cases (18%) had peripapillary, and the others had macular lesions. Before treatment, all cases had subretinal fluid (SRF) causing visual deterioration. Nine cases (41%) had serous retinal detachments; mean basal diameter (BD) was 8.6 (5-14) mm, and tumour thickness (TT) was 3.7 (2.5-7) mm. The median radiation dose was 15 (14-18) Gy. After SRS, mean BD regressed to 5.6 (3-9) mm and TT to 1.7 (0.5-4) mm. SRF disappeared in 18 cases (82%) and decreased significantly in the remaining 4 cases. Visual acuity improved in 21 cases (95%) and stayed stable in one case; the mean increase was 5 + 3.3 Snellen lines. In subgroup analysis, tumours greater than 3.7 mm in thickness had significantly more Snellen line increases than those < 3.7 mm (p=0.023). Patients younger than 40 showed a significantly higher rise in Snellen visual acuity than older cases (p=0.001). None of our patients developed radiation retinopathy or radiation-related complications during the follow-up.

Conclusion: Stereotactic radiosurgery with Cyberknife provided excellent visual outcomes with absorption of subretinal fluid and tumour regression in circumscribed or diffuse choroidal hemangioma without toxicity.

Simultaneous Multiple Brain Metastases SRS/SRT: An Evaluation of Dose Coverage Uncertainty Induced By Intra-Fraction Patient Motion during Beam Delivery

Presenter

Xiaoming Chen

Fox Chase, USA

Xiaoming Chen, Lili Chen, Chang Ming Charlie Ma

Fox Chase Cancer Center, USA

Purpose: Treating multiple lesions simultaneously by using a single-isocenter plan is increasingly used for brain metastasis management. However, the treatment accuracy may be compromised due to the intra-fraction head motion, especially for lesions which are far from the treatment isocenter. This study aimed to evaluate the intra-fraction motion-induced dose coverage uncertainty during simultaneous multi-met SRS/SRT by using patient motion tracking data.

Methods: Patient intra-fraction motion data were retrieved from CyberKnife treatment records and include eight patients with a total of 100 lesions (11-15 lesions per patient). The intra-fraction head motion (n = 6616 time points), defined as position deviation from the planned position, was analyzed for each patient. The motion includes patient’s translation (Ant-Post, Sup-Inf, Lt-Rt) and rotation (yaw, pitch, and roll) and was calculated through registering KVs to plan DRRs. These intra-fraction motion data of each patient were then used to calculate the shift of each lesion in that patient. The dose coverage for each lesion after shift was re-calculated using the original plan and the DVH for each lesion was compared to that of the original plan.

Results: The patient motion-induced shift of lesions has a range of [0.4, 2.3]mm (mean: 1.2+/-0.40mm, based on a 50% likelihood threshold). The Rx dose coverage for each lesion changed from average 99.7+/-0.48% (range: 98% – 100%) to 89.2+/-10.24% (range: 54.5% – 100%). The loss of target coverage is associated with the target distance to the treatment isocenter, and small-sized lesion is more sensitive to intra-fraction motion regarding dose coverage change.

Conclusion: Intra-fraction motion can induce a significant drop of the dose coverage for certain lesions during multiple-target brain SRS/SRT (e.g., up to 45.5% decrease). Motion compensation is definitely needed as is used in Cyberknife, or a proper PTV margin and motion reduction device should be used for linac-based multiple-target brain SRS/SRT.

Multicenter approach to guide plan optimization of robotic intracranial SRS/SRT

Presenter

Sara Broggi

San Raffaele, Italy

Laura Masi1, Valeria Landoni2, Sara Broggi3, Roberta Castriconi3, Marcello Serra4, Anna Stefania Martinotti5, Irene Redaelli5, Maria Cristina Frassanito6, Carmelo Siragusa7, Elena De Martin8, Raffaela Doro1, Antonella Soriani2, Alessia Tudda3, Antonella Del Vecchio3, Claudio Fiorino3

1IFCA, Department of Medical Physics and Radiation Oncology, Firenze, Italy. 2IRCCS Regina Elena National Cancer Institute, Medical Physics Department, Roma, Italy. 3IRCCS San Raffaele Scientific Institute, Medical Physics, Milano, Italy. 4Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, Department of Radiation Oncology, Napoli, Italy. 5Centro Diagnostico Italiano, Cyberknife Department, Milano, Italy. 6Mater Dei Hospital, Città di Bari Hospital spa, Cyberknife Department, Bari, Italy. 7A.O.U. Policlinico G. Martino, Medical Physics Unit, Messina, Italy. 8Fondazione IRCCS Istituto Neurologico Carlo Besta, Health Department, Milano, Italy

Purpose/Objective:

Conformity and steep dose fall-off are fundamental requisites for intracranial stereotactic treatments. This study analyzed inter-institute dose gradient variability of CyberKnife (CK) brain SRS/SRT plans. The aim was to investigate the feasibility of simple predictive models to better guide and possibly automate intracranial SRS/SRT planning optimization.

Material/Methods: Seven CK centers joined the present study developed within a broader Italian Multi-Institutional project. Three- hundred clinical plans, created for brain single lesions distant from serial critical structures and treated between 2018 and 2023, were retrospectively enrolled and analyzed. A minimum of 30 to a maximum of 64 cases were enrolled per participant. For each case, geometrical/anatomical, dosimetric and planning details were reported. PTV median volume was 1.44 cc (range 0.06 to 29.9 cc) and lesions were treated in single (211), three (73), four (3), and five (13) fractions schedules with dose prescriptions ranging from 14 Gy to 40 Gy. Centers were equipped with different CK systems: one S7, two M6, two VSI, two G4. Plans were created for Fixed (148), Iris (136) and MLC (16) collimator using different optimization algorithms (VOLO (228), Sequential (39) and Simplex (33)). Prescription dose, minimal prescription isodose, planning optimization approach were specific for each single center. For each plan, conformity index (CI) and Dose gradient index (DGI) were estimated according to Reynolds1 formula. According to this definition, the higher the DGI value the steeper the dose fall-off: DGI values ≥ 100 corresponds to a gradient ≤ 0.3 cm, whereas any additional millimeter corresponds to a loss of 10 DGI points. The equivalent radii of volumes defined by a set of isodose lines (100%, 85%, 50%, 30%) were also calculated 2. Data analysis focused on the correlation between PTV (volume and radius) and parameters quantifying the dose fall off. Patients were stratified into six group by PTV size: Group I (0-1 cc), II (1-3 cc), III (3-5 cc), IV (5-10 cc), V (10-15 cc), VI (15-40 cc). For each group, the DGI average value was defined as “Ideal” and the minimum acceptable DGI (Minimal) as the value rejecting the lowest 10% of cases. To determine the Minimal values a normal distribution of DGIs was assumed. The analysis was repeated restricting to plans with a conformity index (CI) < 1.2 considered an ideal condition for brain SRS plans1.

Results:

CI and DGI median values were respectively 1.09 (0.96-2.23) and 84.77 (range 19.62-108). DGI as a function of PTV volume is shown in figure 1. A strong significant correlation (p<0.0001) was found between PTV size and DGI with Pearson’s r= -0.78 (95% Confidence Interval: -0.82 to -0.73). DGI ideal values were 95, 82, 77, 71, 59 and 52 for group I, II, III, IV, V and VI respectively. The corresponding minimal DGI values were 86, 73, 67, 59, 43, 36. The rate of DGI passing the minimal criteria was about 90% independently of the group. Considering each center separately, the passing rate with respect to the multicenter Minimal values, ranged from 43% to 100% over the six groups. The inter-institute variability of DGI, expressed in terms of standard deviation, increased with target volume from 6.7 for group I to 12.47 for group VI. Restricting to plans with CI<1.2 (n=220), ideal DGI values remain within 1.4% of the values calculated over all cases. Radii of volumes included in 100%, 85%, 50% and 30% isodose lines are shown in figure 2 as a function of PTV radius together with the R2 values for the corresponding linear regression models. The linear fitting showed a good accuracy. R2 ranged from 0.958 (30% isodose) to 0.994 (100% isodose). When considering only plans with CI<1.20, R2 values increased uniformly (0.966-0.997).

S3585 Physics – Dose prediction, optimisation and applications of photon and electron planning ESTRO 2024

Conclusion: An acceptable inter-institute variability in terms of dose gradient was found for CK single lesion intracranial SRS/SRT, although few systematic differences between centers may be appreciated. DGI values can help planners in avoiding the creation of suboptimal plans and can be useful tools for QA audit and tutorial/education process. The good linear fitting between PTV radius and isodose lines radii, can be useful to automatically generate shell constraints and consequently partially automate plan optimization. Our analysis validated the feasibility of using multicenter data to create easy-to-use generalizable predictive models for CK intracranial SRS/SRT planning.

Keywords: Brain SRS, predictive model, multicenter

References:

1.T.A. Reynolds et.al. Int J Radiation Oncol Biol Phys, Vol. 106, No. 3, pp. 604e611, 2020 2.S. Yu et.al. J Appl Clin Med Phys 2021; 22:3:48–5
3.The study was supported by an AIRC grant (IG23150)

Retreatment for Resistant or Recurrent Pain in Trigeminal Neuralgia Using Frameless LINAC Radiosurgery

Presenter

Pantaleo Romanelli

Centro Diagnostico Italiano, Milano, Italy

Pantaleo Romanelli, Giancarlo Beltramo, Livia Corinna Bianchi, Achille Bergantin, Isa Bossi Zanetti, Anna Stefania Martinotti, Irene Redaelli

CyberKnife Center, Centro Diagnostico Italiano, Milano, Italy

Objectives:

Recurrent or resistant pain is a well know occurrence following conventional surgical and radiosurgical treatments for Trigeminal Neuralgia (TN). Frameless LINAC radiosurgery is an emerging treatment for TN. The long term results of this novel and completely noninvasive treatment modality for TN have been previously reported . Safety and efficacy of retreatments using frameless LINAC radiosurgery to improve pain control in patients resistant to first treatment or in patients with recurrent pain are poorly known . A large series of patients undergoing frameless LINAC radiosurgery retreatment for resistant or recurrent TN pain is here reported.

Methods:

This paper illustrates pain control and complications after frameless radiosurgery for TN pain resistant or recurrent after frameless LINAC radiosurgery. Frameless radiosurgery for TN was introduced at Stanford University in 2002. The senior author refined this technique over the years and introduced a TN frameless radiosurgery protocol at the Cyberknife Center of CDI (Milano,Italy). This protocol aims to deliver an homogeneous radiation dose (60 Gy) to an extended segment of the trigeminal nerve (6 mm) without hot spots. Retreatments are performed on patients resistant to treatment (no pain improvement within 6 months) or in patients with temporary clinical benefit and subsequent recurrent pain. A lower dose (45 Gy) is typically prescribed for the second treatment to reduce the risk of sensory complications. Pain control and sensory complications (facial numbness) are assessed using the dedicated BNI scales, as previously described.

Results:

575 TN patients have been treated at CDI with frameless LINAC radiosurgery. 482 patients (83,8%) required a single treatment to achieve long-term pain control while 93 patients (16,2%) underwent retreatment for resistant or recurrent trigeminal pain. The retreatment group includes 48 men and 45 women, Pain was right-sided in 54 and left-sided in 39. Mean age was 61,3 years (range 29-89). 15 patients (16,1%) had no response to the first treatment (resistant pain) and were retreated within six months. 25 patients (26,9 %) had recurrent pain after a short interval of well-being and were retreated within 12 months. 53 patients (57%) were retreated for recurrent pain at later time (12 to 136 months). Mean interval between first and second treatment was 24,2 months (range 4-136 months). Three patients required a third treatment. Two patients with multiple sclerosis had recurrent pain on the other side and required bilateral treatment( not a retreatment on the same nerve). Mean dose delivered at the first treatment was 58,5 Gy (range; 30-75 Gy), prescribed to a mean 82,6% isodose (range 77-89). Mean dose delivered at the second treatment was 45,3 Gy (range: 30-63 Gy), prescribed to a mean 83,2% isodose (range:79-89). Mean treatment volume at the first treatment was 28,8 mm³ (range: 9-55). Mean treatment volume at the second treatment was 25,1 mm³ (range: 8-44,4). One year after the second treatment satisfactory pain control was achieved in 85 out of 93 pts (91.4%). This pain control rate remained stable after 3 and 5 years. Sensory complications appeared in 27 patients out of 93 (29,3%) after 1 year. Somewhat bothersome facial numbness (BNI grade III) was found in 18 retreated patients (19,4%) while very bothersome facial numbness (BNI grade IV) developed in 3 patients (3,2%).

Conclusion(s):

Radiosurgical retreatment is occasionally needed to achieve or restore pain control in TN patients with resistant or recurrent trigeminal pain, In this series, 16,2% of the patients treated underwent retreatment, achieving long-term pain control. This comes at the price of a higher rate of sensory complications: 29,3% of retreated patients developed grade III-IV facial numbness while previous reports from our group show that the rate of sensory complications including patients with a single treatment is much lower (5%). Further studies are needed to confirm these results and assess wheter the rate of sensory complications can be reduced while preserving long-term pain control. However, it should be noted that the pain control and complications following frameless radiosurgery compare favourably with any other surgical technique available to treat TN.

Clinical outcome and dosimetric feasibility of hippocampal sparing whole brain radiotherapy

Presenter

Bhuvana J.

Ahmedabad, India

Bhuvana J, Ankita Parikh, Suryanarayan Kunikullaya U

Gujarat Cancer and Research Institute, B J Medical college, Radiation Oncology, Ahmedabad, India

Purpose/Objective: Whole brain radiotherapy (WBRT) is one of the mainstay of treatment of brain metastases especially. But, even though cranial irradiation improves overall survival, the associated neurocognitive deficits and declining quality of life have brought this treatment modality under scrutiny. Radiation-induced injury to the neural stem cells in the hippocampal formation is associated with deficits in learning, memory and spatial processing. The aim of this study is to appraise the feasibility of avoiding hippocampus while delivering WBRT in helical TomoTherapy (HT). Also, we aim to evaluate the benefits of HS-WBRT in regards to preventing cognitive decline and assess if the theoretical benefit of sparing hippocampus clinically translate to preservation of neurocognition using standard neurocognitive function(NCF) test instruments.

Material/Methods: We conducted a prospective study on the feasibility of HS-WBRT in 26 patients who presented with brain metastases and the resulting benefit of hippocampal sparing on NCF. All patients were older than 18 years of age and had karnofsky performance status score> 70. Histopathological evidence of malignancy was procured from all patients. Patients with prior cranial irradiation, lesions involving hippocampus, radiographic evidence of hydrocephalus and/or clinical suspicion of leptomeningeal spread were excluded. Selected patients were planned for HS-WBRT in HT and subsequently underwent CT simulation and MRI brain imaging. After CT-MRI images registeration, contouring was done in accordance with standard contouring guidelines and hippocampal contouring atlas for RTOG 0933. Total dose of 30Gy in 10 fractions was prescribed to PTV and the treatment was delivered ibyRadixact X9 helical tomotherapy (Accuray, Sunnyvale, USA). Conformity and homogeneity of dose distribution were analysed using target coverage (TC), homogeneity index (HI), V90, V95, prescription isodose volume to target volume ratio (PITV) and maximum dose divided by the prescription dose (MDPD). NCF was assessed by test batteries namely HVLT-R and MMSE. Quality of life was evaluated by FACT BR questionnaire. Patients underwent these test batteries prior to the start of WBRT, at completion of RT and monthly till 6 months post radiotherapy.

Results: Median age of presentation was 55 years. 54% of patients were males and remaining 46% were females. 77% had KPS score >90. Only 42% of patients presented with solitary lesion in brain and the rest had multiple brain metastases. Overall survival was 92.3%. Mean tumor regression assessed three months post HS-WBRT was 62%. Average PTV volume was 1525.20cc with the maximum volume being 1776.0cc. Dose to 2% volume of PTV was 31Gy± 0.33. Minimum dose to 98% volume of PTV was 26Gy±1.5. D90% was 29.80Gy ±0.2. 96.2% target volume received 95% of prescription dose while 98% volume received 90% of the prescription dose. Average distance between Hippocampus and V95 is 10.17mm. Average time duration for one fraction was 19 minutes±4min. The mean TC for whole brain was 0.95±0.16, mean CN was 0.92±0.16 and mean HI was 0.1±0.04. The mean PITV and MDPD was 0.94±0.18 and 1.1±0.15 respectively. The mean volume of hippocampus was 4.54cc ±1.43. The minimum dose covering 100% hippocampus volume was 5.2Gy. Maximum dose to hippocampus was 14.4Gy while the mean dose was 7.4Gy. MMSE scores significantly improved from baseline after WBRT but there was no strong association with hippocampus dosage till 4 months post WBRT (p<0.01). HVLT-R parameters demonstrated improvement from baseline values and post 4 months of WBRT, had significant negative association with hippocampus dosimetry. Immediate recall had statistically significant negative correlations with minimum and maximum hippocampal dosage after 4months post RT. Immediate recognition and delayed recall showed strong negative association with mean dosage in addition to minimum and maximum hippocampus dosage. FACT-BR scores showed a significant increase from baseline to completion and had strong positive correlation to MMSE scores and HVLT-R parameters. The strength of association was persistent from baseline to 6months post RT.

Conclusion: We conclude that helical TomoTherapy is capable of delivering an highly conformal and homogenous HS-WBRT plan while achieving dose constraints of hippocampus in a reasonable treatment time. Also, anatomical avoidance of hippocampus contribute to preservation of neurocognition and maintain quality of life. Since, deleterious effect of hippocampus irradiation on neurocognitive function is more pronounced after 4months of HS-WBRT, longer administration of NCF test batteries is desirable. The feasibility of HS-WBRT predicts successful sparing of hippocampus without affecting target coverage even in definitive radiotherapy and should be considered for treatment of curable brain tumors, where the advantage of hippocampal sparing will be more profound.

Keywords: Hippocampal sparing, WBRT, TomoTherapy

Research on Thread Effect in Helical TomoTherapy Radiotherapy for Cervical Cancer

Presenter

Li Guang

Chongqing University Cancer Hospital, China

Luo, F. Jin, Y. Wang, M. Q. Yang, T. Qiu, W. Hu, T. Wang, S. Li, and X. Tan
Chongqing University Cancer Hospital

Purpose/Objective(s): In spatially fractionated radiation therapy (SFRT), there is an interaction between irradiated cells, and high-dose irradiated cells might inhibit the growth of low-dose irradiated cells, defined as cohort effect. Given the inherent dose ripple in Helical Tomotherapy (HT), the cohort effect might be triggered by thread effect of HT. Therefore, in this study, a new HT SFRT scheme was proposed and tested by plan simulation, cell experiment and clinical cases.

Materials/Methods: This study adopted Hela cells, and enrolled fourteen patients diagnosed as carcinoma of uterine cervix with stage IA to IIIC. CT images were scanned and both planning target volume (PTV) and organs at risk (OARs) were delineated by the same experienced radiation oncologist. TomoHD system with a 6-MV photon beam simulated HT SFRT plans and also simulated both conventional HT (CHT) and SBRT plans for comparison. The dose threshold triggering the cohort effect was explored via proliferative capacity changes of cells and then regarded as the daily dose of HT SFRT and SBRT plans. The total dose was clinically considered. This study analyzed and compared the physical and biological doses of PTV and OARs, treatment efficiency, TCP and NTCP. The universal survival curve (USC) model was used. Meanwhile, the Poisson and Lyman-Kutcher-Burman (LKB) model calculated TCP and NTCP, respectively.

Results: The HT SFRT plan chosen the combination of FW=5.084 cm, Pitch=0.5 and MF=2.0. A significant decrease in cell viability was observed in HT SFRT with an 8-Gy dose, compared to the CHT. In delivery time, the HT SFRT outperformed SBRT (15.10 minutes vs. 26.43 minutes, p<0.05). In total time, both HT SFRT and SBRT have the significant advantages. For D_max, D_mean, D_median, and D_2% of PTV, HT SFRT in 3 fractions and SBRT was lower than CHT, but HT SFRT in 4 fractions has higher metrics. For bladder and bladder wall, the D_15cc, D_mean and D_max of HT SFRT and SBRT were less than CHT. There were similar values for colon, small intestine and spinal cord between HT SFRT in 4 fractions and CHT. The dose metrics of rectum and femoral head from HT SFRT in 4 fractions were higher than CHT, but this phenomenon can be changed by tightening dose constraints. TCP reached 99.91%-100.00% in all schemes. NTCP of bladder and bladder wall from HT SFRT in 4 fractions was better than CHT, and the two schemes were similar for NTCP of the rectum, colon, and small bowel. But, NTCP of femoral head was greater in HT SFRT with 4 fractions and the phenomenon was also flipped by tightening dose constraints.

Conclusion: The thread effect of HT would trigger the cohort effect. The scheme of HT SFRT in 4 fractions is an excellent option for prospective clinical trial design in cases where dose constraints of normal tissue become more stringent.

Outcomes of Pelvic Reirradiation with Stereotactic Radiotherapy for Gynaecological Cancer Recurrence

Presenter

Susan Lalondrelle

The Royal Marsden NHS Foundation Trust, UK

Benjamin J Thomas¹, Kallol Bhadra¹, Ian Zing Tan¹, Lei Wang¹, Alexandra Taylor^1,2, Susan Lalondrelle^1,2

¹The Royal Marsden NHS Foundation Trust, Department of Radiotherapy, London, United Kingdom. ²Institute of Cancer Research, Division of Radiotherapy and Imaging, London, United Kingdom

Purpose/Objective: Pelvic recurrence of gynaecological cancer is associated with significant morbidity and can be challenging to treat, particularly when arising in a previously irradiated site. For cases of oligo-relapse a targeted approach is favourable, avoiding the need for systemic therapy. For instances where surgery is not feasible due to anatomical proximity of critical structures or would result in morbidity, reirradiation using highly conformal techniques such as stereotactic radiotherapy (SBRT) to radical doses is increasingly used.

There is however limited published data regarding long-term efficacy and safety of pelvic reirradiation using SBRT in gynaecological malignancies^1–3, and a lack of guidance on case selection, technique, dose and fractionation⁴. We present an analysis of our institutional experience of using SBRT for gynaecological cancer reirradiation to

identify efficacy, toxicity and other factors for appropriate case selection.

Material/Methods: Patients treated with pelvic SBRT reirradiation at our institution for histologically proven gynaecological malignancies between July 2012 and January 2021 were identified from local records. Eligibility for SBRT pelvic reirradiation included lymph node or soft tissue recurrence in the pelvis or para-aortic region or positive margin after surgical resection, GTV <6cm max diameter, 1-3 sites of metastatic relapse, life expectancy >6 months, no significant toxicity from previous radiation, ideally >6 months since initial radiation treatment, WHO Performance Status ≤2. Dose constraints for previously irradiated normal tissue were crudely estimated from degree of overlap with the primary RT fields and subtracted from published SBRT constraints5, incorporating time repair calculation where appropriate. Treatment was delivered on C-arm linac, Cyberknife and MR-linac platforms. Data for analysis was collected from hospital electronic records and radiotherapy treatment planning systems. We recorded demographic, planning and follow up data to evaluate for the endpoints of local, regional and distant failure, PFS and OS, as well as acute and chronic toxicity data (CTCAE grading), dosimetric data, treatment site and subsequent lines of treatment. Patients were censored at their last recorded follow-up or up to September 2023.

Outcome data was correlated with primary tumour site, GTV/CTV volume and time from primary radiotherapy to reirradiation. Statistical analysis was performed using written code from Python 3.10 in PyCharm CE and Lifeline package for formulating K-M curves.

Results: 73 patients were identified who had undergone SBRT pelvic reirradiation: 8 patients received 2 courses of SBRT (4 receiving contemporaneous SBRT to 2 treatment sites, 4 receiving sequential SBRT due to disease progression following first SBRT course). Treatment data is included in Table 1.

Median OS was 43.5 months (95% CI 33.8 to 69.9 months) (Figure 1). Median PFS was 12.9 months (95% CI 7.9 to 19.5 months) (Figure 2) and median time to local failure of treated lesion was 35.7 months (95% CI 24.7 months to not reached). For cervix versus uterine cancer relapse the median OS was 36.6 months (95% CI 19.7 months to not reached) versus 69.9 months (95% CI 38.6 months to not reached), median PFS was 7.4 months (95% CI 3.6 – 35.7 months) versus 16.1 months (95% CI 10.7 to 30.2 months). Time from primary radiotherapy (r = 0.74) but not GTV/CTV volume (r = 0.25) correlated with longer time to treatment failure. SBRT reirradiation was well tolerated with acute G3 toxicity reported in 2 patients (1x diarrhoea, 1x fatigue). Late G3 toxicity was documented in 2 patients (1x Nausea, 1x Vaginal Stricture), occurring >2 years after treatment.

Conclusion: In selected patients with oligometastatic pelvic relapse of gynaecological cancer following previous pelvic radiotherapy, SBRT reirradiation is an effective and safe treatment modality. SBRT reirradiation can provide durable local control and delay time to systemic therapy by >12 months. Our outcomes are comparable to other smaller published case series^1,2.

Keywords: SBRT, Reirradiation, Gynaecology

References: 1. Ling DC, Vargo JA, Burton SA, Heron DE, Beriwal S. Salvage Curative-Intent Reirradiation Stereotactic Body Radiation Therapy for Isolated Pelvic and/or Paraortic Recurrences of Gynecologic Malignancies. Pract Radiat Oncol. 2019;9(6):418-425. doi:10.1016/j.prro.2019.05.012

Park HJ, Chang AR, Seo Y, et al. Stereotactic Body Radiotherapy for Recurrent or Oligometastatic Uterine Cervix Cancer: A Cooperative Study of the Korean Radiation Oncology Group (KROG 14-11). Anticancer Res. 2015;35(9):5103-5110.
Seo Y, Kim MS, Yoo HJ, et al. Salvage stereotactic body radiotherapy for locally recurrent uterine cervix cancer at the pelvic sidewall: Feasibility and complication. Asia Pac J Clin Oncol. 2016;12(2):e280-288. doi:10.1111/ajco.12185
Slevin F, Aitken K, Alongi F, et al. An international Delphi consensus for pelvic stereotactic ablative radiotherapy re-irradiation. Radiother Oncol. 2021;164:104-114. doi:10.1016/j.radonc.2021.09.010
Timmerman RD. An overview of hypofractionation and introduction to this issue of seminars in radiation oncology. Semin Radiat Oncol. 2008;18(4):215-222. doi:10.1016/j.semradonc.2008.04.001

Primary Radiotherapy Modality	EBRT + Brachytherapy = 52
	EBRT only = 18
	Brachytherapy only = 3
Primary Gynaecological Malignancy	Cervix = 33
	Uterus = 27
	Ovary = 6
	Vagina = 4
	Vulva = 3
Time from Primary Radiotherapy to Reirradiation	Median 28 months (Range 4 months to 30 years)
Primary EBRT dose fractionation	Median 45Gy/25# (Range 24Gy/12# to 54Gy/28#)
Prescribed SBRT dose	Median 30Gy/5# (Range 24Gy to 33Gy in 3 to 5 fractions)
Delivery platform	Cyberknife = 53
	C-arm linac = 22
	MR-linac = 6
Treatment site	Soft tissue = 49
	Lymph node = 20
	Positive surgical margin = 12
GTV/CTV volume	Median 18.7cm3 (range 2.1 to 91.8cm3)

Table 1. Treatment data for patient cohort

CYBERNEO Trial: Update of Results at 14 Years of Follow-up

Presenter

Syrine Ben Dhia

Antoine Lacassagne Center, France

Syrine Ben Dhia¹, Renaud Schiappa², Joycelin Gal², Jean-Marc Ferrero³, Philippe Bahadoran⁴, Claire Chapellier⁵, Pierre Yves Bondiau¹

¹Antoine Lacassagne Center, Radiation Oncology, Nice, France. ²Antoine Lacassagne Center, Department of Statistics, Nice, France. ³Antoine Lacassagne Center, Medical Oncology, Nice, France. ⁴CHU Pasteur, Dermatology, Nice, France. ⁵Antoine Lacassagne Center, Medical Imagery, Nice, France

Purpose/Objective: The purpose of the phase I “CYBERNEO” trial was to define the efficacy of the CyberKnife®(CK) for locally advanced (stage III) breast tumors combined to a neo-adjuvant treatment with chemotherapy for patients for whom a conservative surgery could not be considered at the onset. Neoadjuvant chemotherapy (NAC) consisted of 6 cycles: 3 cycles of docetaxel and 3 cycles of 5-fluorouracil-epirubicin-cyclophosphamide (FEC). CK was performed during the second cycle of chemotherapy. Breast surgery was performed six to eight weeks later and conventional breast irradiation without boost, afterwards. The main objective was to define the maximum tolerated dose of hypofractionated radiotherapy concurrent with NAC. We present an updated survival data for patients included in this trial and we evaluate the late toxicities of this combination.

Material/Methods: We updated the survival data of 25 patients treated for stage III breast cancer between 2007 and 2009 at the Antoine Lacassagne Center in Nice and included in the CYBERNEO trial by recording late toxicities and esthetic results.

Results: With a median follow-up of 12 years, 95% CI [10-14], 19 patients (76%) were in remission, 1 patient had a controlled axillary lymph node relapse (4%)and 5 patients (20%) died due to metastatic progression within a median of 5 years after treatment (min: 1, max: 9). Nine patients (36%) had a complete histological response (pCR). The highest percentage of pCR was in the group of patients treated in the 4th stage (28.5 Gy in 4 fractions). Overall survival at 14 years was 71%, 95% CI [53%-94%]. Two patients developed chronic radiation toxicity during follow-up with a fibrosis (8%), of which one was in the 4th stage and one in the 5th stage (31.5 Gy). Three patients (12%) had a change of prosthesis after treatment which for one patient was 24 months after the end of support.

Conclusion: The updated results of the CYBERNEO trial with 14 years of follow-up confirm the satisfactory results in terms of local control with an excellent long-term safety profile.

Keywords: SBRT, breast cancer, neoadjuvant

Moderate hypofractionation with simultaneous integrated boost after conservative surgery for Bca

Presenter

Roberta Tummineri

San Raffaele, Italy

Roberta Tummineri¹, Miriam Torrisi¹, Andrei Fodor¹, Marcella Pasetti¹, Martina Midulla^1,2, Laura Giannini^1,2, Chiara Lucrezia Deantoni¹, Barbara Longobardi³, Roberta Castriconi³, Alessia Tudda³, Claudio Fiorino³, Antonella Del Vecchio³, Nadia Gisella Di Muzio^1,4

¹IRCCS San Raffaele Hospital, Radiation Oncology, Milan, Italy. ²Milano-Bicocca University, Radiation Oncology, Milan, Italy. ³IRCCS San Raffaele Hospital, Medical Physics, Milan, Italy. ⁴Vita-Salute University, Radiation Oncology, Milano, Italy

Purpose/Objective: Moderately hypofractionated radiotherapy (HRT) to whole breast (WB) is the standard treatment for breast cancer (BCa) after conservative surgery. Simultaneous integrated boost (SIB) to the tumor bed is delivered to high risk local recurrence (LR) patients(pts). We report toxicity and outcomes in BCa pts treated with WB+SIB HRT in our Institute.

Material/Methods: From December 2017 to March 2023 260 BCa women were treated with WB+SIB HRT after conservative surgery (right 116, left 144). Median age was 60(29-88) y. Molecular subtypes were: Luminal A 37%, Luminal B Her2- 24.5%, Luminal B Her2+ 14%, HR negative Her2+ 4.5%, Triple negative (TN) 18%. The remaining 2% were in situ BCa.

Chemotherapy (CHT) was prescribed to 132 pts (50.7%): neoadjuvant 14.2%, adjuvant 38%, concomitant 0.3%. Adjuvant endocrine therapy was prescribed for 186 pts (71.5%)(Aromatase Inhibitors or Tamoxifen-/+LH-RH analogue), 48pts (18.5%) underwent HER2-targeted therapy. HRT was delivered with Tomotherapy (79.2%), VMAT (20%) or 3DCRT (0.8%), to a total dose of 40.05Gy to WB and 48Gy to the tumor bed, in 15fractions. Acute and late toxicity and cosmesis were registered according to RTOG, SOMA-LENT and Harvard breast cosmesis scale respectively.

Results: Median follow-up was 38.6 (4.8 – 65.5)months(m). All pts were evaluable for acute toxicity. Late toxicity and cosmesis data were available for 251 pts. Acute and late toxicity are summarized in Table1. Only 3 pts experienced ≥ G3 acute toxicity and only 1≥ G3 late toxicity. Cosmetic outcome according Harvard breast cosmesis scale was available for 241 pts: excellent 41.5%, good 47.5%, fair 8%, poor 3%. Fourty pts (16%) had liponecrosis, evaluated by mammography, ultrasound or MRI. At the last follow-up cardiac events were diagnosed in 4 pts (3 cases of Trastuzumab-induced pericarditis and 1 case of post-CHT heart failure) and lung fibrosis with symptomatic pneumonitis in 2 cases. Raw local control was 98.8%. Only 3 pts (1.2%) had LR(1 TN, 1 Luminal B HER2+, 1 Luminal B HER2-) and 5 pts(2%) (3 Luminal B HER2-, 1 TN, 1 Luminal A), had distant progression(4 bone metastasis, 1 axillar lymph node), at median TTP of 38.4(22.8-44.5) m. Four pts were dead at the last follow-up (2 old age, 1 comorbidity, 1 metastatic lung tumor diagnosed 21m after RT). Median OS was 44.5 (8.9-73.9) m.

Conclusion: In our experience HRT+SIB was feasible with low acute and late toxicity profile, highly satisfying cosmetic outcome and excellent local control. A longer follow-up is necessary to confirm these results.

Table 1: Acute and late toxicity according to RTOG and SOMA-LENT scale respectively.
ACUTE TOXICITY	G0	G1	G2	G3
Breast erythema and/or edema	27 (10%)	194 (75%)	36 (14%)	3 (1%)

LATE TOXICITY	G0	G1	G2	G3
Hyperpigmentation	160 (64%)	89 (35.2%)	2 (0.8%)	0
Edema	204 (81%)	36 (14.5%)	10 (4%)	1 (0.5%)
Fibrosis	211 (84%)	38 (15%)	2 (1%)	0
Pain	230 (91.6%)	20 (8%)	1 (0.4%)	0
Telangiectasia	248 (98.8%)	3 (1.2%)	0	0

Stereotactic Partial Breast Irradiation: 4-year Clinical Results and Cosmetic Outcomes

Presenter

Norbert Meszaros

National Institute of Oncology, Hungary

Norbert Meszaros^1,2, Levente Janvary¹, Viktor Smanyko¹, Tibor Major^1,2, Gabor Stelczer¹, Zoltan Nagy Takacsi^1,2, Csaba Polgar^1,2

¹National Institute of Oncology, Center of Radiotherapy, Budapest, Hungary. ²Semmelweis University, Faculty of Medicine, Department of Oncology, Budapest, Hungary

Purpose/Objective: The aim of this study was to evaluate the clinical results and cosmetic outcomes of 4-fraction stereotactic accelerated partial breast irradiation (SAPBI).

Material/Methods: Between November 2018 and November 2022, 71 patients with low risk early invasive (St I-II) breast cancer underwent BCS were enrolled in our phase II prospective study. SAPBI was performed with Cyber-Knife (CK) M6 machine, to a total dose of 25 Gy (4 x 6.25 Gy, delivered daily). Respiratory movements were followed with implanted gold markers and optical markers using Synchrony system. Corrections for patient displacement and respiratory movement during treatment were performed with the robotic arm. Clinical results, side effects, and cosmetic results were assessed.

Results: In all patients, the treatments were successfully completed, and the dose prescriptions and dose limits were observed. Median follow-up time was 48 months (range:11-60 months). During the follow-up, we did not detect any local or regional recurrence or distant metastases. Acute side effects included Grade 1 (G1) erythema, which occurred in 8 (11.2%) patients, while G1 oedema was observed in 7 (9.8%) cases. G1 pain was reported by 1 (1.4 %) patient. Late side effects included G1 fibrosis in 11 (15.5%), G1 pain in 4 (5.6%) patients respectively. Asymptomatic (G1) fat necrosis occurred in 8 (11.2%) patients. Cosmetic outcome was excellent in 44 (61.9%), good in 24 (33.9%), and fair in 3 (4.2%) patients. No grade 1-2 acute or late side-effect was detected.

Conclusion: SAPBI with CK is a feasible technique for the administration of external beam APBI following BCS for the treatment of low-risk, early-stage invasive breast carcinoma. Our findings are promising, CK-SAPBI delivered with four daily fractions is well tolerated by the patients, with excellent clinical result.

Keywords: Stereotactic, partial breast irradiation,

Surface guided ring gantry radiotherapy in deep inspiration breath hold for breast cancer patients

Presenter

Mustafa Kadhim

Skåne University Hospital, Sweden

Mustafa Kadhim^1,2, André Haraldsson^3,2, Malin Kügele^3,2, Hedda Enocson^3,2, Sven Bäck^1,2, Sofie Ceberg²

¹Radiation physics, Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund, Sweden. ²Medical Radiation Physics, Lund University, Lund, Sweden. 3Radiation Physics, Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund, Sweden

Purpose/Objective: Deep inspiration breath hold (DIBH) is a widely adopted treatment technique for left-sided breast cancer patients which reduces ionising radiation exposure to the heart¹. By reducing the dose to the heart, the rate of cardiac complications and toxicity associated with radiotherapy can be mitigated². Accurate DIBH treatments can be achieved using surface guided radiotherapy (SGRT), a technology that enables real-time monitoring and motion management of breast cancer patients³. In combination with TomoDirect^TM (TD), a fixed-angle beam intensity-modulated radiotherapy (IMRT) treatment technique implemented on the Radixact® (Accuray, Madison, USA)⁴, further dose reductions to the heart could potentially be achieved. We investigated as the first in the world the combination of TD and treatment in DIBH using SGRT. Technical challenges for the SGRT system need to be addressed, both the risk of DIBH-signal loss due to camera occlusion in the deep ring gantry bore of the Radixact® and signal stability during constant couch movement. Moreover, a dosimetric investigation motivating the new combination of the techniques is warranted. Thus, the aim of this study is to: 1) investigate the compatibility and feasibility of DIBH utilising SGRT for TD treatments of breast cancer in the Radixact® and 2) measure and compare dosimetric parameters between TD in DIBH and in free breathing (FB) for breast cancer patients.

Material/Methods: To investigate the camera occlusion in the deep bore ring gantry of the Radixact®, surface images (SI) of four healthy volunteers using the Catalyst⁺HD^TM (C-RAD Positioning AB, Uppsala, Sweden) three-camera system were evaluated. The patient setup was done outside the bore at the virtual iso-center, 70 cm from the treatment iso-center (inside the bore). The SGRT system uses a couch tracking laser to track the reference surface during couch movement. The SI coverage and DIBH-signal were evaluated at and beyond the treatment iso-center of the Radixact® For the dosimetric investigation, 20 left-sided breast cancer patients receiving tangential radiotherapy were retrospectively enrolled. For all patients, treatment plans in both FB and DIBH were generated and measured. The plan quality and surface image accuracy were investigated for simulated respiratory motions using a Delta⁴Phantom+ (ScandiDos, Uppsala, Sweden) installed on a HexaMotion (ScandiDos, Uppsala, Sweden) platform. The absorbed dose to the planning target volume (PTV) and organs at risk (OARs) was evaluated for FB and DIBH, respectively. Two-sided paired Wilcoxon signed-ranks tests were performed on the dose-volume histograms (DVH) to investigate significance difference in dosimetric parameters.

Results: The SGRT system maintained adequate surface coverage and an accurate DIBH-signal at depths averaging 33 cm and 42 cm beyond the treatment iso-center during constant couch speed. Due to the steeper angle of the patient scanned inside the bore and loss of surface images from the two side cameras, effects of occlusion in the clavicular and neck regions were observed for all volunteers. The surface coverage was also influenced by the longitudinal and vertical couch positions within the gantry, the gantry geometry, and patient morphology (Figure 1). Accurate detection of the simulated respiratory motion using the HexaMotion platform was obtained for all cases by the Catalyst⁺HD^TM system during constant couch speed. Significant difference in the dose to the heart and left anterior descending artery (LAD) was found between the DIBH and FB plans as the DIBH plans offered a median (range) average dose reduction up to 27% (13-33%) and 40% (26-49%) (p <0.001) to the heart and LAD respectively. As for the near-maximum dose (D2%) to the heart and LAD, the median (range) dose reduction was 50.0% (47-58%) and 47.0% (42-56%) (p <0.001), respectively. No significant difference between DIBH and FB was observed in the average dose to the PTV and ipsilateral lung, nor in the conformity and homogeneity indices.

Conclusion: The real-time surface image coverage and DIBH-signal accuracy were minimally affected by camera occlusion and couch translation in practical clinical settings. The DIBH treatment technique showed a significant reduction of absorbed dose to the heart and LAD compared to FB using TomoDirect^TM radiotherapy. These results demonstrate the feasibility and dosimetric advantage of combining SGRT and DIBH with TomoDirect^TM on the Radixact® ring gantry system for breast cancer treatments.

Keywords: Tomotherapy, Ring gantry bore, DIBH breast cancer

References:

Shah, C. et al. Cardiac dose sparing and avoidance techniques in breast cancer radiotherapy. Radiotherapy and Oncology (2014) doi:10.1016/j.radonc.2014.04.009.
Darby, S. C. et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 368, 987–98 (2013).
Al‐Hallaq, H. A. et al. AAPM task group report 302: Surface‐guided radiotherapy. Med Phys 49, (2022).
Franco, P. et al. TomoDirect: An efficient means to deliver radiation at static angles with tomotherapy. Tumori Journal 97, 498–502 (2011).

Figure 1. The reduction in surface image coverage due to camera occlusion and surface morphology at various positions from the treatment iso-center of the Radixact. The vertical postion was 4.0 cm above teh treatment iso-center. A) surface coverage at the virtual iso-center, B) at the treatment iso-center, C), D) and E) illustrate the surface coverage at 16, 30, and 40 cm beyond the treatment iso-center. F) a measured cut-off in the DIBH-signal 40.0cm beyond the iso-center for this specific volunteer.

Left breast cancer dosimetry with Accuray VOLO Ultra optimizer: a comparison with DIBH

Presenter

Patrizia Urso

Gruppo Ospedaliero Moncucco, Italy

Patrizia Urso, Nathan A Corradini, Giorgio Ballerini, Laura Negretti, Cristina Vite, Alessandra Franzetti-Pellenda

Gruppo Ospedaliero Moncucco, Radiotherapy, Lugano, Switzerland

Purpose/Objective: Even if the radiotherapy for breast cancer is well-known to improve local control and overall survival, clinically induced late side effects on heart and lung for left breast cancer treatments is a serious issue for the health of patients [1]. Aim of this study is the evaluation of dosimetric objectives, in terms of target coverage and organ at risk (OAR) sparing, obtained by the Accuray Precision v.3 treatment planning system (TPS), for Radixact and TomoTherapy systems, recently upgraded with the VOLO^TMUltra optimizer. Results intend to be compared to the dosimetry related to the Deep Inspiration Breath Hold technique (DIBH) reported in the scientific literature, considered one of the most effective approaches in the reduction of the dose to heart and ipsilateral lung [2].

Material/Methods: The analysis deals with the dosimetric results related to the whole set of women treated to the whole breast at the Gruppo Ospedaliero Moncucco, starting from the introduction of VOLO^TMUltra (i.e. from February 2022 to September 2023).

The two techniques, direct (TD) and helical (TH), were used depending on geometry and complexity of the target, preferring as much as possible the TD technique in order to reduce low dose to the OARs. Prescription dose to the whole breast was 50 Gy/25 fx or 42.4 Gy/16 fx. A minimum coverage of 95% of PTV volume by at least 95% of prescribed dose and the maximum volume covered by 107% of prescription dose was required to be less than 1 cc. Constraints to OARs were based on both the international and internal guidelines.

Results: The whole sample included 66 treatment plans, 39 performed using TD (26 with 42.4 Gy/16 fx and 13 with 50 Gy/25 fx) and 27 using TH (11 with 42.4 Gy/16 fx, 16 with 50 Gy/25 fx). The TD plans had a mean beam on time of 168.8±26.5 sec, while TH were about 400.6±74.7 sec, with an average gantry period of 17.2±3.5 sec. On the average, mean dose covering the planning target volume (PTV) was 99.4% for TD and 99.9% for TH, V 95%=96.1±1.7% and 95.9±1.4%, with V107%=0.2±0.3 cc and 0.4±1.1 cc for TD and TH, respectively. Regarding dose to the OARs, detailed results are described in table 1, reported as average and standard deviation.

Briefly, the heart mean doses, for the two fractionations 42.4 Gy/50 Gy, were 1.0±0.5/1.1±0.4 Gy and 1.7±0.7/2.0±0.7 Gy for TD and TH respectively, resulting comparable with the DIBH values reported in the recent meta-analysis [3], ranging between 0.9 and 2.7 Gy. Similarly, for ipsilateral lung the mean dose was 4.4±1.1/5.2±0.9 Gy and 5.1±0.6/5.3±0.9 Gy for TD and TH respectively, that is included in the range of DIBH for the left lung (0.59-14.9 Gy).

Also for LAD, the mean values were 4.3±3.7/5.0±3.5 Gy and 5.0±1.4/4.7±1.9 Gy for TD and TH respectively, that falls within the reported range (0.4-9.4 Gy). Results were also comparable in terms of near maximum dose (D 0.03cc).

Conclusion: Results clearly show that the dosimetric values, obtained with the new algorithm VOLO^TMUltra of TPS Precision v.3 for Radixact and TomoTherapy systems, are largely comparable with dosimetry to OARs obtained by the DIBH technique reported in the literature, while maintaining target coverage. TD and TH treatments in free breathing may be a good alternative to DIBH when it is not appliable or not available. Moreover, this goal can be enhanced by the use of surface guided radiation therapy (SGRT) during treatment delivery.

Keywords: VOLO Ultra, Heart dose, DIBH

References: [1] Darby SC, Ewertz M, McGale P et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 2013; 368:987-98 http://dx.doi.org/10.1056/NEJMoa1209825

[2] Nissen HD, Appelt AL Improved heart, lung and target dose with deep inspiration breath hold in a large clinical series of breast cancer patients. 2013 Radiot Oncol 106(28-32) http://dx.doi.org/10.106.j.radonc.2012.10.016

[3] Lai J et al Meta-analysis of deep inspiration breath hold (DIBH) versus free breathing (FB) in postoperative radiotherapy for left-side breast cancer. 2020 Breast Cancer 27(299-307) http://dx.doi.org/10.1007/s12282-01901023-9

Preoperative Single-Fraction RT for Early Stage BC: Preliminary Results From CRYSTAL Phase I/II Study

Presenter

Maria Zerella

IEO, Italy

Maria Alessia Zerella¹, Mattia Zaffaroni¹, Giovanni Carlo Mazzola¹, Giuseppe Ronci¹, Samantha Dicuonzo¹, Damaris Patricia Rojas¹, Anna Morra¹, Marianna Alessandra Gerardi¹, Cristiana Fodor¹, Elena Rondi², Sabrina Vigorito², Silvia Penco³, Manuela Sargenti⁴, Elisa Vicini⁴, Viviana Enrica Galimberti⁴, Sara Gandini⁵, Giulia Cursano⁶, Elisa De Camilli⁶, Giuseppe Ronci⁶, Federica Cattani², Paolo Veronesi^4,7, Roberto Orecchia⁸, Barbara Alicja Jereczek-Fossa^1,7, Maria Cristina Leonardi¹

¹European Institute of Oncology, Radiotherapy, Milan, Italy. ²European Institute of Oncology, Unit of Medical Physics, Milan, Italy. ³European Institute of Oncology, Breast Radiology, Milan, Italy. ⁴European Institute of Oncology, Breast Surgery, Milan, Italy. ⁵European Institute of Oncology, Experimental Oncology, Milan, Italy. ⁶European Institute of Oncology, Pathology, Milan, Italy. ⁷University of Milan, Oncology and Hemato-oncology, Milan, Italy. ⁸European Institute of Oncology, Scientific Directorate, Milan, Italy

Purpose/Objective: As of today, the main strategies for early-stage breast cancer treatment include breast-conserving surgery (BCS) and WBRT. Given that the majority of local recurrences occured in close proximity of the tumor bed, APBI, which delivers a larger dosage per fraction to the tumor bed during a shorter treatment duration, is becoming more and more popular as a viable option for selected BC patients. This study aims to report first findings from the CRYSTAL trial, which uses CyberKnife to deliver ablative preoperative RT in a single fraction.

Material/Methods: CRYSTAL trial (NCT04679454) is a monocentric phase I/II, single-arm and open-label study which enrolls patients to receive an ablative dose (18–24 Gy) to the tumor with CyberKnife before the surgery. The primary endpoint for the phase I study is the identification of the maximum tolerated dose (MTD) which meets a specific target toxicity level (no grade 3-4 toxicity). For the phase II study, the primary aim is the evaluation of treatment efficacy measured in terms of pathological complete response rate.

Results: A total of 14 patients with a median age at enrollment of 66.8 years (IQR 63.4 – 69.0) were treated within the study. Nine of them have been enrolled and treated within the phase I of the study (3 patients for each dose step: 18-21 24 Gy) while five were treated within the phase II with 24 Gy in single fraction. Stage at diagnosis was T1N0 for nine patients and T2N0 for 5 patients (luminal A for 10 patients, luminal B for 1 patient, luminal B-HER2+ for 2 patient and triple negative histology for 1 patient). Median PTV volume was 15.1 cm3 (range 3.6-47.8 cm3). At pre-surgery MRI 7 patients experienced stability disease, 4 patients a partial response and one patient a complete response, with a median disease extension reduction of 17.9%. Median time to surgery was 33 days (range 28 – 40 days) with 3 patients who underwent mastectomy and 11 QUAD+BLS. One post-surgical complications (liponecrosis) has been reported. All patients except one experienced a reduction in Ki67 proliferation index (median change between biopsy and histologic exam of 7%). Eleven among the 14 treated patients have received post-operative RT according to study protocol, with two patients receiving also chemotherapy. No G>2 acute toxicities have been reported and only one G1 chronic toxicity (breast pain) has been reported at last follow-up. 1-year follow-up was available for 9 out of 14 patients. At a medium follow up of 13.1 months (range 1.4 – 23.3 months) two patients developed a regional relapse and two patients a second tumor in another site. All the other patients are alive with no evidence of disease.

Conclusion: The present analysis reports preliminary results of the first 14 patients enrolled in the study. These preliminary data support the feasibility and safety of preoperative APBI which might be considered as an attractive treatment strategy in early BC setting. Updated data with additional patients, longer follow-up and findings that will become available from similar ongoing investigations will give a clearer indication about this innovative approach.

Keywords: preoperative radiotherapy, radiosurgery

Efficacy and Toxicity of Moderately Hypofractionated Radiotherapy Via Helical TomoTherapy Versus Conventional Radiotherapy Combined with Concurrent Chemotherapy for Patients with Unresectable Stage III Non-small Cell Lung Cancer: A Multicenter, Randomized Phase III Trial

Presenter

XiaoHong Xu

Zhongshan Hospital, China

Jian He, Wenhan Huang, Qi Zhang, Shaonan Fan, Xiaohong Xu

Zhongshan Hospital, Fudan University, Department of Radiation Oncology, Shanghai, China

Chinese clinical trial registration: ChiCTR1800017367

Purpose/Objective: The standard treatment schedule for unresectable stage III non-small-cell lung cancer (NSCLC) delivers 60 Gy in 30 fractions combined with concurrent chemotherapy, but an alternative strategy that can deliver a moderately hypofractionated radiotherapy (Hypo-RT) is found. This study aimed to compare the efficacy and toxicity of helical tomotherapy (HT)–based moderately Hypo-RT versus conventional fractionated radiotherapy (Con-RT) in unresectable stage III NSCLC.

Material/Methods: This is a randomized, multicenter, non-blinded, phase 3 clinical trial. Eligible patients were randomized to the experimental group (Hypo-RT: 60 Gy in 20 fractions) or control group (Con-RT: 60 Gy in 30 fractions). All patients received 2 cycles of concurrent platinum-based chemotherapy plus 2 cycles of consolidation therapy. The primary endpoint was 3-year overall survival (OS) rate (intention-to-treat [ITT] population). The secondary endpoints were progression-free survival (PFS), and treatment-related adverse events (TRAE).

Results: A total of 146 patients were finally enrolled from July 27, 2018 to November 1, 2021 . Seventy-three patients each were assigned to the experimental group and control group. The median follow-up was 46 months. The 3-year OS was 58.36% in the Hypo-RT versus 38.39% in the Con-RT (P = 0. 02). The median OS from randomization was 41 months in the Hypo-RT group and 30 months in the Con-RT group (HR, 0.61; 95% CI, 0.395–0.939; P = 0. 022). No significant differences in grade 2 or greater TRAEs were found between the two groups.

Conclusion: This clinical trial shows that moderately Hypo-RT using HT improves the OS in patients with unresectable stage III NSCLC, with similar toxicity rates compared with Con-RT.

Keywords: NSCLC,helical tomotherapy (HT),chemoradiotherapy

Optimization of Treatment Plan Parameters Used in Helical Tomotherapy for Small Cell Lung Cancer Patients with Extensive Pleural Metastasis

Presenter

Longyan Duan

Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

L. Duan¹, W. Qi¹, C. Li¹, J. Y. Chen^1,2, and S. Zhao¹
¹Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, ²Shanghai Key Laboratory of Proton-therapy, Shanghai, China

Purpose/Objective(s): The study aimed to evaluate the impact of various parameters (field width: FW, pitch factor: PF, and modulation factor: MF) on the quality of treatment plans and treatment time, and identify the optimal combination of plan parameters in helical tomotherapy (HT) technology for small cell lung cancer patients with extensive pleura metastasis (SCLC-EPM).

Materials/Methods: A total of four extensive stage SCLC patients with EPM were included for analysis. Each patient’s target volume and organs at risk (OARs) included PTV, left lung, right lung, sum lung, heart, esophagus, spinal cord. For each patient, 27 treatments were created, consisting of different combination of planning parameters (FW = 1, 2.5, 5 cm; PF = 0.215, 0.287, 0.43; MF = 2.4, 3, 3.6). Default values used in the study were FW = 2.5 cm, PF = 0.287 and MF = 3. The reference plan was optimized for the default values, which was assumed to result in the best dose distribution and treatment time. Finally, 108 plans were created. Each plan was analyzed for dose distribution and treatment time. Dose distribution indices included homogeneity index (HI), conformity index (CI), D_95%, D_90%, D_2% for PTV, D_mean, D_max, V_5Gy, V_20Gy, V_25Gy, V_30Gy for OARs.

Results: FW could impact the dose distribution for both the target volume and OARs, particularly for homogeneity, right lung, liver, and esophagus. Meanwhile, FW emerged as the most influential parameter affecting treatment time, resulting in a significant average time reduction of more than half. A tighter PF could slightly reduce OARs dose, especially for the left lung, sum of lung, and liver without increasing the treatment time. MF could impact the dose distribution, especially for the lung. But no obvious differences were observed for CI an HI under varied MFs conditions. The treatment time increased gradually with the rise in MFs, but the increase was modest. After thoracic radiation, three patients archived partial response and on patient with stable disease at 6 months. No severe lung toxicities could be observed in these four patients.

Conclusion: Considering the balance between plan quality and treatment time, the study suggested that the optimal parameter combination in the HT technique for SCLC-EPM was FW:2.5 cm, PF:0.287, and MF:3. EPM-radiation was efficient and safety for a highly-selected SCLC-EPM patients after first-line chemotherapy with or without immunotherapy.

Radiation-Related Late Toxicities Following Total Marrow Irradiation Transplant Conditioning Regimens

Presenter

Colton Ladbury

City of Hope, USA

C.J. Ladbury1, S. V. Dandapani1, C. Han1, S. K. Hui1, D. Yang2, G. Marcucci3, J. Rosenthal3, A. M. Monzr3, R. Nakamura3, A. Stein3, A. Liu1, and J. Y. C. Wong1

1Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, 2Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, 3Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA

Purpose/Objective: Total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI) have been developed as a component of organ sparing myeloablative conditioning hematopoietic cell transplant (HCT) regimens via delivery using intensity-modulated radiation therapy, with the goal of achieving reduced toxicities and potentially dose-escalation. However, long-term toxicities after TMI/TMLI are not well characterized. This study sought to prospectively quantify pulmonary, renal, thyroid, and cataract toxicities as part of a trial that monitored after TMI/TMLI.

Materials/Methods: A total of 302 patients with primarily multiple myeloma or acute leukemia undergoing HCT with TMI/TMLI conditioning were prospectively followed after treatment as part of an IRB-approved prospective trial. Follow-up included pulmonary function tests, serum creatinine, glomerular filtration rate, thyroid panel, and ophthalmologic examinations performed at 100 days, 6 months, and annually thereafter, though not all patients had assessments for each toxicity. Median TMI dose was 12.5 Gy (10-20 Gy) delivered at 1.5 to 2.0 Gy twice per day at a dose-rate of 200 cGy/min. Radiation-related toxicities including pulmonary toxicity, renal toxicity, hypothyroidism, and cataract formation after HCT were evaluated using cumulative incidence, reported at 8 years. Patients with organ impairment preceding transplant were excluded.

Results: Median age was 48 years (range 9-72). Median follow-up (range) for all patients was 2.2 (0.0-15.1) years and for patients alive at the time of last follow-up (n=58), 6.3 (3.0-8.3) years. Mean organ doses in Gy were lung 7.1, kidneys 6.7, thyroid 6.8, and lens 2.5. The cumulative incidence of radiation pneumonitis (RP) was 0.5%. The cumulative incidence of infection and RP (I/RP) was 35.4% (95%CI: 24.9-46.1%). Mean lung dose <8 Gy predicted for numerically lower cumulative rates of I/RP (30.5% vs 51.0%, P=.10). No radiation-induced renal toxicity was noted. Cumulative incidence of elevated TSH was 16.5% (95%CI: 8.2-27.4%) with 14.1% (95%CI: 6.0-25.5%) requiring replacement therapy. Cumulative incidence of cataract formation was 25% (95%CI: 13.5-39.0%) with 12.0% (95%CI: 4.6-23.2%) requiring surgery.

Conclusion: To our knowledge, this represents the largest study to date reporting long term toxicities after TMI/TMLI. TMI/TMLI is associated with lower rates of pulmonary toxicity, renal toxicity, and hypothyroidism compared with historical cohorts treated with conventional total body irradiation. Rates of cataract formation were comparable. This study supports continued evaluation of TMI/TMLI conditioning regimens in patients undergoing HCT.

Clinical Outcomes Following Stereotactic Ablative Body Radiotherapy to Central Lung Tumours

Presenter

Julie Duong

Mount Vernon Cancer Centre, UK

Julie Duong, Riya Patel, Prasana Nariyangadu, Karen Venables, Anup Vinayan, Mark Harrison, Peter Ostler, Nihal Shah, Yat Tsang, Suraiya Dubash

Mount Vernon Cancer Centre, Oncology, London, United Kingdom

Purpose/Objective: The safety and effectiveness of using stereotactic ablative body radiotherapy (SABR) for central lung tumours is associated with increased toxicity. We present our centres experience and clinical outcomes.

Materials/Methods: The study encompasses patients diagnosed with both primary and oligometastatic central lung tumours, specifically those positioned within 2 cm of the proximal bronchial tree, mediastinal and pericardial pleura, as well as the brachial plexus. This retrospective analysis includes all patients treated with a specialized robotic stereotactic RT machine from May 2016 till July 2023. The treatment protocol employed consisted of administering 50 Gray in 5 fractions, which were delivered on consecutive days propelled by image-guided RT under autonomous breathing, all while under the meticulous surveillance of real-time motion tracking. An integral component of this study is the scrutiny of the maximum dose absorbed by the trachea & bronchus. Follow-ups were systematically arranged 6 weeks post-treatment, semi-annually for the subsequent two years, and annually for years 3 through 5.

Furthermore, the overall survival (OS) rate was computed using Kaplan-Meier methodology, and post-radiotherapy toxicity data was classified following the CTCAE v4.0 protocol.

Results: Of the 68 eligible patients, median age was 73 yrs (range 50-90). Non-small cell lung cancer was the most prominent primary tumour (n=62), followed by colorectal (n=8), cervix (n=1), and renal (n=1). The median tumour volume reached 12.40cc (ranging from 1.24 to 77.30cc). The median maximum dose (Dmax 0.5cc) to the trachea and bronchus was recorded to be 23.2Gy (0.7-59.5Gy range). The median follow-up period lasted 16 months (spanning from 1-67), with a projected median OS of 39 months and an OS at the 12-month mark of 82%. Recorded toxicity rates remained low, with grade 1 toxicity including fatigue and grade 2 comprising of cough and dyspnoea.

Importantly, no evidence was detected for grade 3 or higher toxicities.

Conclusion: Our study substantiates existing literature conclusions by demonstrating that the utilization of SABR for central lung tumours yields acceptable overall survival rates and manageable post-radiotherapy toxicity levels. Elevated grade toxicities were not evident, thereby underscoring the safety and practicality of this treatment approach.

Keywords: SABR, Central Lung Tumours

References:

Chang JY, Senan S, Paul MA, Mehran RJ, Louie AV, Balter P, Groen HJ, McRae SE, Widder J, Feng L, van den Borne BE, Munsell MF, Hurkmans C, Berry DA, van Werkhoven E, Kresl JJ, Dingemans AM, Dawood O, Haasbeek CJ, Carpenter LS, De Jaeger K, Komaki R, Slotman BJ, Smit EF, Roth JA. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol. 2015 Jun;16(6):630-7. doi: 10.1016/S1470-2045(15)70168-3. Epub 2015 May 13. Erratum in: Lancet Oncol. 2015 Sep;16(9):e427. PMID: 25981812; PMCID: PMC4489408.

Modern Radiotherapy for Extended Cutaneous Lesions from Lymphomas: Results from a Multicenter Study

Presenter

Mario Levis

University of Torino, Italy

Mario Levis¹, Fabio Matrone², Gabriele Simontacchi³, Michela Buglione⁴, Michael Oertel⁵, Patrizia Ciammella⁶, Pierina, Navarria⁷, Marco Galaverni⁸, Emanuela Olmetto³, Sara Bartoncini¹, Khaled Elsayad⁵, Andrea Guerini⁴, Monica, Mangoni⁹, Chiara Cavallin¹, Stephan Rehn⁵, Emanuele Alì⁶, Damiano Dei⁷, Paola De Franco¹⁰, Giuliana Pascale¹¹, Ilenia Iamundo De Cumis¹², Alessandra Donofrio², Claudia Grondelli⁸, Francesca Clot¹, Hans T Eich⁵, Umberto Ricardi

¹University of Torino, Department of Oncology, Torino, Italy. ²Centro di Riferimento Oncologico CRO Aviano, Department of Radiation Oncology, Aviano, Italy. ³AOU Careggi, Radiotherapy unit, Firenze, Italy. ⁴University of Brescia, Department of Oncology, Brescia, Italy. ⁵University Hospital Muenster, Department of Radiation Oncology, Muenster, Germany. ⁶AUSL IRCCS di Reggio Emilia, Radiation Oncology Unit, Reggio Emilia, Italy. ⁷Humanitas Research Hospital, Radiotherapy and Radiosurgery Department, Rozzano, Milano, Italy. ⁸AOU di Parma, Radiotherapy unit, Parma, Italy. ⁹University of Firenze, Department of Experimental and clinical biomedical sciences “Mario Serio”, Firenze, Italy. ¹⁰Ospedale Vito Fazzi, U.O. Radioterapia Oncologica, Lecce, Italy. ¹¹IRCCS Dino Amadori, Radiotherapy Unit, Meldola, Italy. ¹²Businco Hospital, ARNAS G. Brotzu, Department of Radiation Oncology, Cagliari, Italy

Purpose/Objective: Cutaneous lymphomas are a heterogeneous group of highly radiosensitive diseases and radiotherapy (RT) is a highly effective skin directed therapy in case of either primary or secondary skin involvement. Given the superficial localization of these lesions, electron beam therapy is largely adopted and delivered locally (EBT) or comprehensively to the total skin (TSEBT), depending on clinical indication(1). However, the treatment of extended or irregularly shaped cutaneous lesions is often unfeasible with EBT for technical reasons or not indicated with TSEBT for clinical reasons. Modern and highly conformal delivery techniques, such as intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), may be a possible solution to solve this unmeet clinical need. Literature data on the adoption of modern techniques in this setting are scarse and limited to case reports (2-3). In this multi-institutional collaboration, we report real-world data in the largest published series to date with the aim of demonstrating the safety and the efficacy of IMRT and VMAT to treat extended primary or secondary cutaneous lesions in lymphoma patients.

Material/Methods: We conducted a multi-institutional retrospective analysis, including data from 10 Italian and 1 German institutions. The study was approved by the ethical committee of each participating center. Eligibility criteria included a histological confirmation of lymphoproliferative disorder, receipt of a RT course planned with a high dose-gradient technique (IMRT or VMAT) and delivered with a conventional LINAC or with helical tomotherapy (HT) between 2010 and 2023 and age >=18 at the time of treatment. Primary endpoints were overall response rate (ORR) and acute treatment-related morbidity, defined as the appearance of any skin adverse event (AE). ORR was defined as the achievement of complete response (CR) or partial response (PR) and was estimated at least 1 month after the end S1151 Clinical – Haematology ESTRO 2024 of RT. Acute skin AEs were estimated within 3 months by the end of RT and scored with CTCAE 5.0 classification. Secondary endpoints were local control (LC) and progression-free survival (PFS). Time to event endpoints were calculated from the starting date of RT with the Kaplan-Meier method, and were compared among subgroups using the log-rank test. Univariate and Multivariable (MVA) Cox proportional hazards were calculated to estimate the effect of covariates on patients’ outcome. Logistic regression models were used to investigate the correlation between RT-related factors and clinical toxicity events.

Results: 125 patients were included: 79 (63%) were male and median age at treatment was 69 (range 22-94) years. The median number of previous treatment lines was 1 (range 0-11). Indolent B-cell, diffuse large B-cell and T-cell histology were detected in 24%, 22% and 42% of the patients respectively. Before treatment, 45% of the patients had local skin symptoms such as itching, pain or ulceration in the treated site. RT was delivered with HT in 74% and with LINAC in 26% of patients. Median prescribed dose was 30 Gy (range 4-50 Gy), delivered in daily fractions of 2 Gy (range 1.6-8 Gy) to a median PTV volume of 488 cc (range 7-7871 cc). ORR at 1 month was 97% (61% CR and 36% PR). Acute skin AEs of any grade (G>=1) were detected in 73%, G>=2 events in 22% and G3 events only in 3% of patients. No G4-5 events were observed (Table). Total RT dose >30 Gy was related with higher risk of developing any grade AE (85% vs 54%, p700 cc was related with higher risk of G>=2 AEs (34% vs 16%, p = 0.03). Daily RT dose had no impact on acute AEs. With a median follow-up of 15 months, 1-year LC and PFS were 84% and 60%, respectively (Figure). On MVA, PTV volume >700 cc had a negative impact on LC (HR=5.48; p=0.01). The presence of skin symptoms before RT (HR=2.90; p=0.003), T-cell histology (HR=1.59; p=0.04) and again PTV volume >700 cc (HR=2.90; p=0.003) negatively affected PFS. The prescribed RT dose did not affect neither LC nor PFS.

Conclusion: In our study, highly conformal delivery techniques proved to be effective to treat extended cutaneous lesions from lymphomas, achieving good LC rates. Moreover, these techniques can be safely administered, as the risk of G3 events is very low. Doses >30 Gy should be discouraged in this particular setting for the higher risk of cutaneous AEs, without a positive impact on disease control.

Keywords: Cutaneous lymphoma, IMRT/VMAT; Modern Radiotherapy

References: (1) Specht L, Dabaja B, Illidge T, et al. Modern radiation therapy for primary cutaneous lymphomas: field and dose guidelines from the International Lymphoma Radiation Oncology Group. IJROBP 2015;92:32-39( (2) Samant RS, Fox GW, Gerig LH, et al. Total scalp radiation using image-guided IMRT for progressive cutaneous Tcell lymphoma. BJR 2009;82:e122-e125 (3) Ostheimer C, Janich M, Hubsch P, et al. Radiat Oncol 2014;9:82

Phase II Trial of TMLI 20 Gy in Combination with Cyclophosphamide and Etoposide in Patients with Poor-Risk Acute Leukemia

Presenter

Jeffrey Wong

City of Hope, USA

J. Y. C. Wong¹, A. M. Monzr², A. Salhotra², S. V. Dandapani¹, Y. Wang³, J. Palmer³, C. Han¹, A. Liu¹, E. H. Radany¹, I. Aldoss², H. Ali², L. Farol², F. Sahebi², R. Spielberger², G. Marcucci², R. Nakamura², E. Smith², S. K. Hui¹, S. J. Forman², and A. Stein²
¹Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, ²Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, ³Division of Biostatistics, City of Hope National Medical Center, Duarte, CA

Purpose/Objective(s): Patients with relapsed or refractory (R/R) acute leukemia have a poor prognosis with current hematopoietic cell transplant (HCT) options. Total marrow and lymphoid irradiation (TMLI), which delivers escalated targeted radiation doses to bone marrow (BM) while reducing doses to multiple organs at risk (OARs), was developed to address this unmet need. We report results of a phase II study (NCT02446964) which combined TMLI (20 Gy to BM/ lymph nodes/ spleen; 12 Gy to liver/brain) with cyclophosphamide (Cy) and etoposide (VP16) as a conditioning regimen in patients with R/R acute leukemia undergoing allogeneic HCT.

Materials/Methods: TMLI was administered 2 Gy twice a day on days -9 to day -5, VP16 60mg/kg on day -4, and Cy 100mg/kg on day -2. Graft versus host disease (GVHD) prophylaxis was tacrolimus and sirolimus. The primary endpoint was progression free survival (PFS), and secondary endpoints included overall survival (OS), non-relapse mortality (NRM), and toxicity.

Results: 74 patients (AML n=56, ALL n=18) were treated from 5/2014-9/2020. Median age was 40.1 (16.5 – 59.3) years. 51 (69%) patients were induction failures. 72 (97%) patients had detectable marrow blasts and 36 (49%) detectable circulating blasts just prior to TMLI. The day+30 BM biopsy CR rate was 92%. Engraftment occurred for all subjects. Mean organ doses (Gy) were lung 8.8, kidneys 7.3, heart 7.5, thyroid 8.0, lens 2.5 and lower GI 10.2. Grade =2 Bearman scale toxicities were stomatitis (Gr2 n=17, Gr3 n=5), gastrointestinal (Gr2 n=10, Gr3 n=4), renal (Gr2 n=1, Gr3 n=5), hepatic (Gr2 n=3, Gr3 n=2), central nervous system (Gr2 n=3, Gr3 n=1), bladder (Gr2 n=4), pulmonary (Gr2 n=1), and cardiac (Gr2 n=1). Median follow-up was 1.8 years (range: 0.1-5.9) and for surviving patients 4.2 years (range: 2.0-5.9). The 2-year PFS and 2-year OS were 31.1% (95%CI: 21%-42%) and 45.9% (95%CI: 34%-57%). The cumulative incidence of NRM at day+100, year 1, and year 2 were 4.1% (95%CI: 1-10%), 8.1% (95%CI: 3-16%), and 12% (95%CI: 6-21%), respectively. Peripheral blasts = 20% prior to TMLI was associated with higher risk of disease relapse/progression or death.

Conclusion: To our knowledge this is the largest prospective experience using TMLI 20 Gy. TMLI results in significant dose reduction to OARs allowing for target doses of 20 Gy to be safely delivered in combination with VP16 and Cy in patients < 60 years of age. This regimen provides an effective HCT option for patients with R/R acute leukemia, with PFS, OS and NRM rates that compare favorably to historical results. Given these results, TMLI 20 Gy followed by post-transplant Cy is currently being evaluated as a potential replacement for standard TBI conditioning in patients with AML in complete remission (NCT03467386).

5-Year Outcomes from PACE B: An International Phase III Randomized Controlled Trial Comparing Stereotactic Body Radiotherapy (SBRT) vs. Conventionally Fractionated or Moderately Hypo Fractionated External Beam Radiotherapy for Localized Prostate Cancer

Presenter

Nick van As

The Royal Marsden NHS Foundation Trust, UK

N. van As¹, A. Tree¹, J. Patel², P. Ostler³, H. Van Der Voet⁴, D.A. Loblaw⁵, W. Chu⁶, D. Ford⁷, S. Tolan⁸, S. Jain⁹, J.G. Armstrong^10,11, P. Camilleri¹², K. Kancherla¹³, J. Frew¹⁴, A. Chan¹⁵, O. Naismith¹, G. Manning², S. Brown², C. Griffin², E. Hall²
¹The Royal Marsden NHS Foundation Trust, London, United Kingdom, ²The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, United Kingdom, ³Mount Vernon Cancer Centre, Northwood, United Kingdom, ⁴The James Cook University Hospital, Middlesbrough, United Kingdom, ⁵Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁶Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁷Queen Elizabeth Hospital, Birmingham, United Kingdom, ⁸The Clatterbridge Cancer Centre, Liverpool, United Kingdom, ⁹Queen’s University Belfast, Belfast, United Kingdom, ¹⁰Cancer Trials Ireland, Dublin, Ireland, ¹¹St Luke’s Radiation Oncology Network, Dublin, Ireland, ¹²Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom, ¹³University Hospitals Leicester, Leicester, United Kingdom, ¹⁴Freeman Hospital, Newcastle, United Kingdom, ¹⁵University Hospitals Coventry and Warwickshire, Coventry, United Kingdom

Purpose/Objective(s): External beam radiotherapy (EBRT) is a curative treatment for Localized Prostate Cancer (LPCa). Large randomized controlled trials (RCTs) have shown moderately hypo fractionated regimens (2.5 – 3 Gy/fraction(f)) as non-inferior to 2Gy/f regimens. PACE-B aims to demonstrate non-inferiority of SBRT compared to conventionally or moderately hypo fractionated regimens for biochemical and/or clinical failure (BCF).

Materials/Methods: PACE (NCT01584258) is an international phase III open-label multiple-cohort RCT. Men with LPCa, stage T1-T2, ≤ Gleason 3 + 4, PSA ≤ 20 ng/mL, unsuitable for surgery or preferring EBRT, were eligible. Participants (pts) were randomized (1:1) to SBRT (36.25 Gy / 5f in 1-2 weeks (wks)) or control radiotherapy (CRT) (78 Gy / 39 f over 7.5 wks, or 62 Gy / 20 f in 4 wks) to the planning target volume. Androgen deprivation therapy was not permitted. The primary endpoint was freedom from biochemical (BF)/clinical (CF) failure. BF is based on PSA rises, commencement of ADT or date of orchiectomy and CF is based on local recurrence, nodal recurrence, distant metastases and death from prostate cancer. 858 pts were needed to rule out 6% inferiority (80% power, one-sided alpha 5%) assuming 85% event-free rate with CRT, corresponding to a critical hazard ratio (HR) of 1.45. Analysis was done by intention to treat.

Results: 874 pts were randomized from 38 centers (n=441 (CRT) and n=433 (SBRT)) between 08/2012 and 01/2018. Baseline characteristics were well balanced across CRT and SBRT groups: median age 69.8 years (IQR 65.4,74.0); median PSA ng/mL (IQR): 8.1 (6.3,11) vs 7.9 (5.5,10.9); NCCN risk group 9.3% low, 90.7% intermediate. With median follow-up of 73.1 months (IQR 62.6, 84.0), 5-year BCF event free-rate (95% CI) was 94.6% (91.9% – 96.4%) vs 95.7% (93.2% – 97.3%) for CRT and SBRT groups respectively. SBRT was non inferior to CRT with unadjusted HR (90% CI) = 0.74 (0.47 – 1.17), p-value for non-inferiority=0.007. The estimated absolute differences in the proportion of patients event free in the SBRT group compared with that in the CRT group at 5 years was: 1.36% (90% CI: 0.87 – 2.80). At 5 years, RTOG grade 2 or worst (G2+) genitourinary toxicity was seen in 3.2% (11/348) pts who received CRT and 5.5% (20/363) pts who received SBRT (p=0.14); RTOG G2+gastrointestinal toxicity was seen in 1/348 receiving CRT and 1/363 received SBRT (p=0.99).

Conclusion: Five-year BCF free rates are high in PACE-B participants. After median follow-up of six years, five-fraction-SBRT is non-inferior to CRT for BCF. SBRT reduces pts attendances, shortens treatment time and 5 fraction SBRT should be a new standard of care for pts with low/favourable intermediate risk LPCa.

The UPRATE trial: feasibility of seminal vesicle PTV-margin reduction with online adaptive SBRT

Presenter

Victor Brand

Erasmus, Netherlands

Victor J. Brand, Maaike T.W. Milder, Femke E. Froklage, Miranda E.M.C. Christianen, Kim C. de Vries, Mischa S. Hoogeman, Luca Incrocci

Erasmus MC Cancer Institute, University Medical Center Rotterdam, Radiotherapy, Rotterdam, Netherlands

Purpose/Objective: The low α/β ratio for prostate cancer (PCa) suggests a benefit of ultra-hypofractionation (UHF). However, for a subgroup of high-risk PCa patients, for whom the seminal vesicles (SV) need to be included in the target volume, UHF can be challenging. Generating clinically acceptable UHF treatment plans is difficult for these patients as the SV require a rather generous PTV-margin (around 8 mm). The UPRATE trial (clinicaltrials.gov; NCT05361902) aims to prove feasibility of SV PTV-margin reduction in low volume metastatic PCa. For this purpose, an online adaptive workflow combining daily replanning, using an in-room CT scanner on rails, and intra-fraction fiducial tracking, as available on the CyberKnife system using 2D KV imaging, is used. Here the results of the first 12 patients, including the observed acute toxicity rates, are reported.

Material/Methods: In this single-arm, single-centre, phase 2 trial, men with histologically and radiologically proven low volume metastatic PCa, referred for local treatment according to the STAMPEDE trial [1] were eligible. After intraprostatic fiducial implantation, patients were treated with six weekly fractions of 6 Gy. All fractions were adapted using the online adaptive workflow for the CyberKnife combining online replanning together with intrafraction fiducial tracking. The clinical target volumes included the prostate and base or entire SV, at the discretion of the treating physician, with PTV-margins of 3 mm around the prostate and 5 mm around the SV. The dose was prescribed to the 95% isodose line aiming for a PTV V95 ≥99% and adherence to all OAR constraints.

Dosimetric coverage of the SV was estimated on a post-fraction CT-scan, on which, after contouring, the adapted plan was rigidly transferred based on a fiducial match with the pre-fraction CT-scan. In case only the base of the SV was part of the target volume, a treatment on the entire SV was simulated and used for analysis. For all participants, SV V95 and relevant OAR-dosimetric parameters were recorded. A treatment was considered successful when, for one patient, a maximum of one out of six fractions showed underdosage of the SV (V95 <99%) on the post-fraction CT-scan.

Regarding adaptation, the online adapted plans and the non-adapted baseline plan made during preparation were compared on SV V95 and relevant OAR-dosimetric parameters, after a rigid transfer onto the post-fraction CT-scan based on a fiducial match.

As per trial protocol, genitourinary (GU) and gastrointestinal (GI) toxicities were recorded prior to, directly after and three months after treatment, using CTCAE version 5.0.

Results: Of the 12 completed treatments analysed, 11/12 were considered successful. One simulated treatment was considered unsuccessful as two out of the six fractions exhibited underdosage of the SV on the post-fraction CT scan. For both fractions, bladder volumes increased substantially (<200 mL pre-fraction to >800 mL post-fraction) resulting in a large posterior/caudal displacement of the SV and subsequently SV V95 of 78.2% and 84.9%, respectively. Of the remaining 11 treatments (consisting of 66 fractions), only two fractions of different patients exhibited SV underdosage on the post-fraction CT-scan. One fraction showed an anterior/cranial displacement of the SV caused by an intrafraction large rectal gas pocket, whereas the second fraction exhibited a posterior/caudal displacement of the SV due to an intrafraction bladder volume increase.

Comparing adaptation to the non-adapted treatment plan, an improvement in the population average SV V95 on the post-fraction CT-scan from 97.6% to 99.3% (aim ≥ 99%) was seen, as well as a slight improvement of the OAR dosimetrics, within the constraints. However, on an individual patient level, adaptation resulted in only one unsuccessful treatment compared to four using non-adapted plans. Looking at the individual fractions, adaptation resulted in a total of only four fractions with SV underdosage compared to a total of 18 fractions for the non adapted plans. Furthermore, the adapted plans resulted in OAR doses adhering to the OAR constraints for 13 of the fractions in which the non-adapted plans did not adhere to the constraints.

Regarding GU and GI toxicity none out of 12 patients reported toxicity more than grade 1. See figure 1 for a detailed bar chart regarding toxicity scores for all patients.

Conclusion: Current preliminary data suggests that a PTV-margin of 5 mm is sufficient to cover the SV when using online adaptation together with intra-fraction fiducial tracking. The treatment is very well tolerated, with a toxicity profile comparable to or even better than reported in the STAMPEDE trial [1]. These preliminary data from the UPRATE trial can be considered a successful first step towards ultra-hypofractionation for high-risk PCa patients when including the entire SV in the target volume.

Keywords: Adaptive, Seminal vesicles, Ultrahypofractionation

References: [1] Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392:2353-66.

SBRT Focal Boost for Localised Prostate Cancer: Primary Outcomes of the SPARC Prospective Trial

Presenter

Binnaz Yasar

The Royal Marsden NHS Foundation Trust, UK

Binnaz Yasar^1,2, Yae-Eun Suh¹, Ewan Chapman³, Luke Nicholls⁴, Daniel Henderson⁵, Caroline Jones6, Kirsty Morrison⁷, Emma Wells¹, Julia Henderson¹, Carole Meehan¹, Aslam Sohaib¹, Helen Taylor¹, Alison Tree^1,2, Nicholas Van As^1,2

¹Royal Marsden NHS Foundation Trust, Urology Unit, London, United Kingdom.²The Institute of Cancer Research, Urology Research, London, United Kingdom. ³St Bartholomew’s Hospital, Radiotherapy department, London, United Kingdom. ⁴University of Queensland, School of Medicine, Brisbane, Australia. ⁵University Hospitals Birmingham NHS Foundation Trust, Radiotherapy department, Birmingham, United Kingdom.⁶Leeds Teaching Hospitals NHS Trust, Physics department, London, United Kingdom. ⁷Guy’s and St Thomas’ NHS Foundation Trust, Radiotherapy department, London, United Kingdom

Purpose/Objective: Dose escalated radiotherapy is associated with better outcomes at the expense of increased toxicity.[1] Stereotactic radiotherapy with dose escalation to the dominant intraprostatic lesion (DIL) is one logical approach to improve disease control in high-risk disease whilst limiting toxicity. In this prospective phase 2 trial, we evaluated the toxicity and quality of life outcomes in participants treated with CyberKnife based stereotactic body radiotherapy (SBRT) with simultaneous integrated boost to the MRI defined DIL in localised prostate cancer.

Material/Methods: SPARC is a single institution phase II prospective trial that was approved by the local Research Ethics Committee (Clinical Trials.gov ID: NCT02145494). Eligible participants were men with newly diagnosed, biopsy-proven localized prostate cancer with unfavourable intermediate to high-risk features with up to two MRI identified DILs. Participants had at least one of the following: Gleason 4+3 or above, MRI defined T3a N0, PSA greater than 20 ng per millilitre.

SBRT was prescribed to 36.25Gy to the prostate delivered on alternative days with a simultaneous boost to DIL up to 47.5Gy as allowed by organs at risk (OAR) constraints delivered by CyberKnife. All participants received androgen deprivation therapy. The primary outcome measure was acute grade 2 and above genitourinary (GU) toxicity. Acute and late GU and gastrointestinal (GI) toxicity using RTOG scoring, biochemical parameters, IPSS, IIEF5, EQ5D quality of life outcomes were assessed at end of treatment (last fraction for SBRT), 2 weeks, 4 weeks and 12 weeks following treatment, then every 3 months for the first 2 years, every 6months from year 2 to 5, and annually thereafter for 10 years.

Results: Between July 2013 and March 2023, 20 participants were enrolled on the study with a median follow-up of 30 months. The median D95 dose to DIL was 47.43Gy. Cumulative acute grade 2 and above genitourinary (GU) and gastrointestinal (GI) toxicity was 25% and 30%, respectively. One patient developed acute grade 3 GU toxicity (5%).

By week 12 post treatment, all grade 2 or above GU and GI toxicity had resolved. There is no late grade 3 GU or GI toxicity to date. IPSS score and urinary quality of life scores recovered to baseline by 6months. Patient-reported outcomes showed no significant change in EQ-5D quality of life scores at 12 weeks and 1 year compared to baseline. There are no cases of biochemical relapse reported to date.

Conclusion: CyberKnife SBRT delivered to a dose of 36.25Gy to the prostate gland and a simultaneous integrated boost to DIL up to 47.5Gy is feasible and well tolerated. Rates of acute and late GU and GI toxicity are comparable to other recent contemporary SBRT trials and series with focal boost.

Keywords: Prostate Cancer, SBRT, dominant lesion

References: [1] Kerkmeijer LGW, Groen VH, Pos FJ, Haustermans K, Monninkhof EM, Robert ;, et al. Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: Results From the FLAME Randomized Phase III Trial. J Clin Oncol . 2021;39:787–96.

Urethra and Bladder Dosimetry in Patients Treated with Prostate SBRT with and without Intra-Prostatic Boost (IPB)

Presenter

Nima Aghdam

Beth Israel, USA

N. Bhargava ∙ M. Hurwitz ∙ L. Bennett ∙ J.A. Aronovitz ∙ D.R. Schmidt ∙ I.D. Kaplan ∙ N. Aghdam
Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA

Purpose:To evaluate the dosimetric and toxicity profiles of stereotactic body radiotherapy (SBRT) for prostate cancer, comparing treatments with and without intraprostatic boost (IPB) to assess feasibility, safety, and effectiveness, with particular attention to urethral and bladder dosimetry.

Materials/Methods: This retrospective study analyzed 349 patients with localized prostate cancer treated between 2018 and 2023. Of these, 266 received SBRT with IPB (cohort A), and 83 received uniform-dose SBRT (cohort B). Patients were treated using a robotic SBRT platform with fiducial tracking. Dosimetric parameters for the urethra, including D0.03cc, D0.3cc, and V40Gy, and for the bladder, including D0.03cc, D5cc, D10cc, and V37Gy, were evaluated. Acute and late toxicities were assessed using CTCAE criteria.

Results: For the urethra, median (range) D0.03cc was 41.8 Gy (38.9–46.8 Gy) and 41.6 Gy (36.2–46.5 Gy), D0.3cc was 41.0 Gy (38.0–46.0 Gy) and 40.9 Gy (34.3–46.0 Gy), and V40Gy was 0.76 cc (0–4.92 cc) and 0.97 cc (0–6.83 cc) for cohorts A and B, respectively. For the bladder, median (range) D0.03cc was 41.2 Gy (29.1–49.0 Gy) and 41.3 Gy (35.7–46.7 Gy), D5cc was 34.5 Gy (17.2–39.5 Gy) and 34.9 Gy (17.9–38.9 Gy), D10cc was 30.1 Gy (14.4–36.4 Gy) and 30.4 Gy (9.6–36.3 Gy), and V37Gy was 2.4 cc (0–8.3 cc) and 2.7 cc (0–7.8 cc) for cohorts A and B, respectively. No statistically significant differences in these parameters were observed between the two cohorts. Late urinary toxicity of grade 3 or higher occurred in 2.25% of patients in the IPB group, with no grade 3 acute toxicities reported.

Conclusion: Intraprostatic boost during SBRT achieves focal dose escalation to dominant intraprostatic lesions (DILs) without significantly increasing urethral or bladder doses or compromising toxicity profiles. These findings support the feasibility and safety of IPB, reinforcing its role in management of localized prostate cancer. Future research should focus on standardizing DIL contouring and exploring adaptive planning techniques to optimize clinical outcomes.

Outcomes of a Phase II Trial of High-Dose Online-Adaptive SBRT for Abdominal Oligometastases

Presenter

Lucy A. van Werkhoven

Erasmus, Netherlands

Lucy A. van Werkhoven, Maaike T.W. Milder, Mischa S. Hoogeman, Remi A. Nout, Joost J. Nuyttens

Erasmus MC Cancer Institute, Radiotherapy, Rotterdam, Netherlands

Purpose/Objective: In the phase II prospective STEAL trial, online adaptive stereotactic body radiotherapy (SBRT) with a library of plans is employed to safely increase the dose to the target for patients with abdominopelvic lymph node oligometastases.

Here, we report the primary endpoint local control, toxicity, and provide insights into the process of selecting the plans from the library.

Material/Methods: Oligometastatic patients with abdominal lymphadenopathies were enrolled in the STEAL trial, and treated with CyberKnife with an integrated CT scanner on rails [1]. Patients were all treated with a total dose of 45 Gy in 5 daily consecutive fractions of 9 Gy. For each patient, a library of 3 plans was created pretreatment: plan A, based on the planning CT; plan B, with OARs contours based on their location on a diagnostic CT scan both with 45 Gy prescribed to the 90% isodose-line; and plan C, based on the planning CT with 45 Gy prescribed to the 80% isodose-line. Before each fraction a CT scan was made with the in-room CT scanner. Next, the planning CT and fraction CT were rigidly matched based on the spine. Based on this match, the dose of the three plans and the target volumes (GTV and PTV) were rigidly transferred to the fraction CT. Organs at Risk (OAR) as contoured in the planning CT were propagated to the fraction CT scan by deformable image registration (DIR). For each plan, relevant DVH parameters such as PTV coverage and dose to bowel (V35) were computed and presented in a tabular format indicating whether they passed or failed. Following a decision tree, the radiotherapy technologist (RTT) selected the best plan of the day, i.e. the plan with the highest target coverage without exceeding OAR constraints. Plan selection took place without interference of a radiation oncologist. The RTT’s underwent training to ensure safe execution of the workflow.

Results: We included 52 patients and performed 55 treatments. The primary tumor was prostate adenocarcinoma in 19 patients (36 %), colorectal in 17 (33%) and 16 patients (31%) had a primary tumor with a different origin. For only 12 patients (22%) plan A was delivered in all fractions and thus received the standard treatment. An adaptive treatment plan was chosen in 58% of the fractions. Plan C was most frequently selected from the library in 45% of the fractions, followed by plan A in 43%. Plan B was chosen in 12% of the fractions. Anatomical variations observed in the fraction CT scan led to replanning for 4 patients, with in 3 cases due to a constraint violation and in 1 patient due to movement of the GTV outside the PTV. A local control of 96% was achieved at 1 year, as shown by the Kaplan Meijer curve displayed in Figure 1. The median overall survival was 49 months (95% CI 39-58). One patient developed a late grade 3 ureter stenosis 2 years after treatment of a left iliacal lymph node. Grade ≤ 2 acute toxicity was reported in 34 patients (62%). Grade ≤2 late toxicity was reported in 4 patients (8%).

Conclusion: The observed low toxicity demonstrates that SBRT with plan-library based online adaptation can be safely employed to treat abdominopelvic lymph node oligometastases. This strategy resulted in a one-year local control rate of 96% with minimal toxicity. Currently, this approach has become the standard of care in our department. Regarding the plan selection process, the treatment is carried out without the need for the involvement of a radiation oncologist.

Keywords: Online adaptive, SBRT, Oligometastases

References: 1. Papalazarou C, Klop GJ, Milder MTW, Marijnissen JPA, Gupta V, Heijmen BJM, Nuyttens JJME, Hoogeman MS. CyberKnife with integrated CT-on-rails: System description and first clinical application for pancreas SBRT. Med Phys. 2017 Sep;44(9):4816-4827.

SBRT and Systemic Therapy for Patients with Oligometastatic Renal Cell Carcinoma

Presenter

Miriam Torrisi

Ospedale San Raffaele, Italy

Miriam Torrisi¹^,2, Chiara Lucrezia Deantoni¹, Andrei Fodor¹, Laura Giannini^1,2, Martina Midulla^1,2, Roberta Tummineri¹, Italo Dell’Oca¹, Sara Broggi³, Antonella Del Vecchio³, Stefano Arcangeli⁴, Nadia Gisella DiMuzio^1,5

¹IRCCS Ospedale San Raffaele, Radioterapia, Milano, Italy. ²Università degli studi Milano-Bicocca, Radioterapia, Monza, Italy. ³IRCCS Ospedale San Raffaele, Fisica Medica, Milano, Italy.⁴IRCCS San Gerardo dei Tintori, Radioterapia, Monza, Italy. ⁵Università Vita Salute San Raffaele, Radioterapia, Milano, Italy

Purpose/Objective: Renal cell carcinoma (RCC) is an aggressive malignancy, and often carries a poor prognosis, especially in metastatic patients. RCC has traditionally been considered radio-resistant with a limited role for conventional fractionation as a local approach. However, since the advent of stereotactic body radiation therapy (SBRT), radiotherapy has been increasingly used in the management of metastatic RCC (mRCC). The aim of our analysis is to evaluate the role of SBRT as Metastasis-Directed Therapy for synchronous and metachronous oligo- metastatic (OMD) RCC pts in terms of local control and delay of prescription of Next-line Systemic Therapy (NEST).

Material/Methods: A monocentric retrospective data collection was performed. Between 02/2019-07/2023, 97 treatments in 61 pts were delivered with CyberKnife™ (Accuray, Sunnyvale, CA, USA). All metastatic sites were considered. Tumor response was evaluated using the response evaluation criteria in solid tumors (RECIST). Time to NEST was calculated from the end of SBRT to the start of any new systemic therapy. Progression-free survival (PFS), Local Control (LC) and overall survival (OS) were calculated via the Kaplan-Meier method.

Results: Median follow-up was 13.9 (0-61.9) months. Median time between primary tumor diagnosis and SBRT for OMD was 62.2 (0-356.7) months. Median prescribed dose was 30 Gy (16-60) in a median of 3 (1-8) fractions, at a median isodose of 80% (63%-85%). For 47 treatments (48.4%) concomitant systemic therapy was prescribed. Median Biological Equivalent Dose (BED), calculated with tumor specific a/b coefficient of 3, was 146.7 (66.7-378) Gy. OS of all pts at 12- and 24-months was 87.1% and 63.6%, respectively. Twelve- and 24-month LRFS was 81.8% and 78.7%, respectively. At the last follow-up NEST was necessary for 11 pts (25 lesions). Median time to NEST was 8 (1.6-30.8) months. NEST-free survival at 12- and 24-months was 70.7% and 63.2%, respectively. Median NEST-free survival for pts with SBRT only was not reached, and was 30.8 months for pts with SBRT and systemic therapy. Six-, 12- and 24 months NEST-free survival was 85.1%, 82%, and 69% for pts with SBRT only vs 76.5%, 56.6% and 56% for pts with SBRT and systemic therapy (p=0.15), probably due to the selection of pts with more advanced disease for systemic therapy.

Conclusion: SBRT is a feasible and effective treatment in patients with mRCC with good LC. These results of combined local and systemic treatments should be verified in prospective trials.

Keywords: kidney, SBRT, metastasis

SABR for Liver De Novo, Repeat, and Induced Oligometastatic Disease

Presenter

Miriam Torrisi

Ospedale San Raffaele, Italy

Miriam Torrisi¹^,2, Chiara Lucrezia Deantoni¹, Laura Giannini^1,2, Andrei Fodor¹, Lucia Perna³, Sara Broggi³, Martina Midulla^1,2, Roberta Tummineri¹, Claudio Fiorino³, Najla Slim¹, Paolo Passoni¹, Antonella Del Vecchio³, Stefano Arcangeli^4,2, Nadia Gisella Di Muzio^1,5

¹IRCCS Ospedale San Raffaele, Radioterapia, Milano, Italy. ²Università degli studi Milano Bicocca, Radioterapia, Monza, Italy. ³IRCCS Ospedale San Raffaele, Fisica Medica, Milano, Italy. ⁴IRCCS San Gerardo dei Tintori, Radioterapia, Monza, Italy. ⁵Università Vita Salute San Raffaele, Radioterapia, Milano, Italy

Purpose/Objective: Non-surgical local ablative approaches for liver metastasis are increasingly used for patients (pts) not eligible for surgery. The role of Stereotactic Ablative Radiotherapy (SABR) in the management of oligometastatic cancer pts have been widely investigated confirming its safety and efficacy. Here we report our results based on the ESTRO EORTC definition of oligometastatic disease (OMD).

Material/Methods: All pts with OMD treated at our institution with SABR from 02/2016- 02/2023, were retrospectively investigated. SABR was delivered with Helical Tomotherapy® (HT) or CyberKnife® (CK). For CK pts a median number of four (3-8) radiopaque gold fiducials were implanted before the treatment. All pts underwent contrast-enhanced simulation CT scan. Based on the metastatic disease history all pts were divided into 3 groups. Group 1 includes de-novo OMD (NOMD) (32 pts), group 2 repeat OMD (ROMD) (14 pts),and group 3 induced OMD (IOMD) (10 pts). Kaplan-Meyer estimate was used to report Overall survival (OS) and Local Relapse Free Survival (LRFS). Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Results: A total of 56 lesions in 40 pts were treated. Median age of the patients at diagnosis was 66 years (29-83). Median follow up was 14.5 months (0.6-81.9). Twenty-five lesions were treated with CK, the remaining 31 with HT. Median number of liver metastases/patient was 4 (1-6). Median GTV was 16.65 (0.3-631.7) cc. Median BED, calculated with tumor specific a/b coefficient, was 100 (59.5-378) Gy. No ≥ G3 toxicities and radiation-induced liver disease (RILD) were recorded. OS at 6- and 12-months of NOMD, ROMD and IOMD were 90%, 84.6%, 80% and 73%, 75.2%, 70% (p=0.4), respectively. Six- and 12-month LRFS for NOMD, ROMD and IOMD was 85.9%, 100%, 100% and 85.9 %, 77.8% and 100%, respectively (p=0.48) (Figure 1).

Conclusion: SABR for liver metastasis in OMD is an effective and well-tolerated in all settings of pts. In our cohort no statistical difference was observed in the 3 main OMD groups. Probably larger cohorts and longer follow-up are needed to observe a difference in groups of patients who theoretically have different prognostics.

Keywords: Liver, SBRT, oligometastasis

Acute Toxicity from PACE-C Comparing Stereotactic Body Radiotherapy (SBRT) with Moderate Hypofractionation (MHRT)

Presenter

Alison Tree

The Royal Marsden NHS Foundation Trust, UK

Alison Tree^1,2, Victoria Hinder³, Andrew Chan⁴, Shaun Tolan⁵, Peter Ostler⁶, Hans Van Der Voet⁷, Kiran Kancherla⁸, Andrew Loblaw⁹, Olivia Naismith¹⁰, Suneil Jain¹¹, Alexander Martin¹², Derek Price¹³, Douglas Brand³, William Chu⁹, John Armstrong¹⁴, Aileen Duffton¹⁵, John Staffurth¹⁶, Julia Pugh³, Georgina Manning³, Stephanie Brown³, Stephanie Burnett³, Clare Griffin³, Emma Hall³, Nicholas Van As^1,2

¹The Royal Marsden Hospitals NHS Foundation Trust, The Royal Marsden Hospital, London, United Kingdom. ²The Institute of Cancer Research, The Institute of Cancer Research, London, United Kingdom. ³The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, United Kingdom. ⁴University Hospitals Coventry & Warwickshire NHS Trust, University Hospitals Coventry & Warwickshire, Warwickshire, United Kingdom. ⁵The Clatterbridge Cancer Centre NHS Foundation Trust, The Clatterbridge Cancer Centre, Liverpool, United Kingdom.⁶The Hillingdon Hospitals NHS Foundation Trust, Mount Vernon Cancer Centre, Northwood, United Kingdom. ⁷South Tees NHS Foundation Trust, The James Cook University Hospital, Middlesbrough, United Kingdom. ⁸University Hospitals of Leicester NHS Trust, University Hospitals of Leicester, Leicester, United Kingdom. ⁹Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, Canada. ¹⁰The Royal Marsden Hospitals NHS Foundation Trust, Radiotherapy Trial Quality Assurance, London, United Kingdom. ¹¹Belfast Health and Social Care Trust, Queen’s University Belfast, Belfast, United Kingdom. ¹²Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, United Kingdom. ¹³Patient and Public Involvement (PPI) representative, Independent, London, United Kingdom.¹⁴Cancer Trials Ireland, St. Luke’s Radiation Oncology Centre, Dublin, Ireland. ¹⁵Beatson West Of Scotland Cancer Centre, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom. ¹⁶Cardiff University, School of Medicine, Cardiff, United Kingdom

Purpose/Objective: The PACE-B trial has established SBRT as a standard of care in low/favourable intermediate risk localised prostate cancer (LPCa). This is the first report of PACE-C which aims to demonstrate non-inferiority of SBRT compared to MHRT for biochemical/clinical failure for intermediate or high-risk LPCa, in combination with androgen deprivation therapy (ADT). Compared to PACE-B, a larger volume of seminal vesicles were permitted to be irradiated in PACE-C hence acute toxicity is of interest; MHRT was 60Gy in 20 fractions (f) rather than the 62Gy/20f used in PACE-B.

Material/Methods: PACE (NCT01584258) is a phase 3 open-label multiple-cohort RCT. Men with LPCa, stage T1c –T3a, ≤ Gleason 4+4, PSA≤30ng/mL were eligible for PACE-C. Between 11/2019 and 06/2022, 1208 pts (51 centres) were randomised (1:1) to SBRT or MHRT; all were planned to receive 6-12 months ADT. SBRT dose was 36.25Gy/5f in 1-2 weeks (wks), MHRT was 60Gy/20 f in 4 wks. Acute toxicity was assessed at baseline, 2-weekly during MHRT/final day of SBRT, and at 2, 4, 8 & 12 wks post-treatment. Primary acute toxicity outcomes were percentage of pts with grade 2 or higher (G2+) RTOG genitourinary (GU) and gastrointestinal (GI) toxicities during the acute period, compared by Χ 2 test (α 0.025 for each outcome), analysis by treatment received. Other key outcomes were percentage G2+ CTCAE GI and GU toxicities (collected post-treatment only) and percentage of pts with minimally clinically important difference (MCID) in EPIC-26 subdomain scores urinary incontinence (UI) (8 points), urinary irritative or obstructive (UO) (6 points) and bowel (5 points).

Results: Characteristics of the MHRT (608 treated/601 allocated) and SBRT (584/607) groups respectively were: median age: 72.4 vs 73.1 years; NCCN intermediate risk 63.3% vs 64.6%, high risk 36.7% vs 35.4%; Gleason score≤3+4: 62.4% vs 59.9%, 4+3: 30.8% vs 35.6%, 4+4: 6.8% vs 4.5%; PSA median (IQR) 8.3 (6-12.4) vs 8.5 (6-12.4).

RTOG G2+ toxicity was not significantly different for GI events (MHRT 69/606 (11.4%) vs SBRT 75/581 (12.9%), p=0.422; G3+ 3/606 (0.5%) vs 2/581 (0.3%)), nor GU events (MHRT 166/605 (27.4%) vs SBRT 160/579 (27.6%) p=0.94; G3+ 10/605 (1.7%) vs 12/579 (2.1%)). There were differences in CTCAE G2+ GI toxicity: MHRT 60/604 (9.9%) vs SBRT 90/584 (15.4%) p=0.004) but not GU: MHRT 170/604 (28.2%) vs SBRT 194/582 (33.3%) p=0.053. Percentage of pts with MCID for MHRT vs SBRT; UI was 187/511 (36.6%) vs 184/496 (37.1%), p=0.869; UO was 324/493 (65.7%) vs 336/478 (70.3%), p=0.127; bowel was 251/514 (48.8%) vs 287/488 (58.8%), p=0.002

Conclusion: Despite an accelerated treatment schedule and a larger treated volume compared to PACE-B, RTOG assessments show similar rates of acute GI and GU toxicity for SBRT and MHRT. CTCAE and EPIC-26 bowel effects are more common after SBRT. Late toxicity and efficacy data are awaited.

Keywords: Prostate cancer, SBRT, Randomised controlled trial