Ultra-hypofractionated Radiotherapy Research Articles

Weekly ultra-hypofractionated radiotherapy in localised prostate cancer

BackgroundModerately hypofractionated radiotherapy regimens or stereotactic body radiotherapy (SBRT) are standard of care for localised prostate cancer. However, some patients are unable or unwilling to travel daily to the radiotherapy department and do not have access to, or are not candidates for, SBRT. For many years, The Royal Marsden Hospital NHS Foundation Trust has offered a weekly ultra-hypofractionated radiotherapy regimen to the prostate (36 Gy in 6 weekly fractions) to patients unable/unwilling to travel daily. MethodsThe current study is a retrospective analysis of all patients with non-metastatic localised prostate cancer receiving this treatment schedule from 2010 to 2015. ResultsA total of 140 patients were included in the analysis, of whom 86 % presented with high risk disease, with 31 % having Gleason Grade Group 4 or 5 disease and 48 % T3 disease or higher. All patients received hormone treatment, and there was often a long interval between start of hormone treatment and start of radiotherapy (median of 11 months), with 34 % of all patients having progressed to non-metastatic castrate-resistant disease prior to start of radiotherapy. Median follow-up was 52 months. Median progression-free survival (PFS) and overall survival (OS) for the whole group was 70 months and 72 months, respectively. PFS and OS in patients with hormone-sensitive disease at time of radiotherapy was not reached and 75 months, respectively; and in patients with castrate-resistant disease at time of radiotherapy it was 20 months and 61 months, respectively. ConclusionOur data shows that a weekly ultra-hypofractionated radiotherapy regimen for prostate cancer could be an option in those patients for whom daily treatment or SBRT is not an option.

Stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer – Acute toxicity and patient-reported outcomes in the prospective, multicenter SMILE phase II trial

BackgroundDue to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial. Materials and methodsA total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and gastrointestinal (GI-) toxicity, as defined by CTCAE v. 5.0 and RTOG as well as patient-reported outcomes according to EORTC QLQ-C30 and -PR25 scores were analyzed at completion of radiotherapy, 6 and 12 weeks after radiotherapy and compared to baseline symptoms. ResultsThere were no toxicity-related treatment discontinuations. At the 12-week follow-up visit, no grade 3 + toxicities were reported according to CTCAE. Up until the 12-week visit, in total 16 patients (23 %) experienced a grade 2 GU or GI toxicity. Toxicity rates peaked at the end of radiation therapy and subsided within the 12-week follow-up period. At the 12-week follow-up visit, no residual grade 2 GU toxicities were reported and 1 patient (1 %) had residual grade 2 enteritic symptoms. With exception to a significant improvement in the emotional functioning score following MRgSBRT, no clinically meaningful changes in the global health status nor in relevant subscores were reported. ConclusionDaily online-adaptive MRgSBRT for localized prostate cancer resulted in an excellent overall toxicity profile without any major negative impact on quality of life.

Adaptive ultra-hypofractionated whole-pelvic radiotherapy in high-risk and very high-risk prostate cancer on 1.5-Tesla MR-Linac: Estimated delivered dose and early toxicity results.

Magnetic resonance (MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation (UHF-WPRT) is a novel approach to radiotherapy for patients with high-risk (HR) and very high-risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac. Ten patients with clinical stage T3a-4N0-1M0-1c PCa, who consecutively received UHF-WPRT, were enrolled prospectively. The contours of the target and organ-at-risks on the position verification-MR (PV-MR), beam-on 3D-MR(Bn-MR), and post-MR (after radiotherapy delivery) were derived from the pre-MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses. In total, we collected 188 MR scans (50 pre-MR, 50 PV-MR, 44 Bn-MR, and 44 post-MR scans). With median 59 min, the mean prostate clinical target volume (CTV)-V100% was 98.59% ± 2.74%, and the mean pelvic CTVp-V100% relative percentages of all scans was 99.60% ± 1.18%. The median V29 Gy change in the rectal wall was -2% (-18% to 20%). With a median follow-up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR-based dosimetry analysis. Chinese Clinical Trial Registry ChiCTR2000033382.

Ultra-hypofractionated prostate cancer radiotherapy: Dosimetric impact of real-time intrafraction prostate motion and daily anatomical changes

PurposeTo retrospectively assess the differences between planned and delivered dose during ultra-hypofractionated (UHF) prostate cancer treatments, by evaluating the dosimetric impact of daily anatomical variations alone, and in combination with prostate intrafraction motion. MethodsProstate intrafraction motion was recorded with a transperineal ultrasound probe in 15 patients treated by UHF radiotherapy (36.25 Gy/5 fractions). The dosimetric objective was to cover 99 % of the clinical target volume with the 100 % prescription isodose line. After treatment, planning CT (pCT) images were deformably registered onto daily Cone Beam CT to generate pseudo-CT for dose accumulation (accumulated CT, aCT). The interplay effect was accounted by synchronizing prostatic shifts and beam geometry. Finally, the shifted dose maps were accumulated (moved-accumulated CT, maCT). ResultsNo significant change in daily CTV volumes was observed. Conversely, CTV V100% was 98.2 ± 0.8 % and 94.7 ± 2.6 % on aCT and maCT, respectively, compared with 99.5 ± 0.2 % on pCT (p < 0.0001). Bladder volume was smaller than planned in 76 % of fractions and D5cc was 33.8 ± 3.2 Gy and 34.4 ± 3.4 Gy on aCT (p = 0.02) and maCT (p = 0.01) compared with the pCT (36.0 ± 1.1 Gy). The rectum was smaller than planned in 50.3 % of fractions, but the dosimetric differences were not statistically significant, except for D1cc, found smaller on the maCT (33.2 ± 3.2 Gy, p = 0.02) compared with the pCT (35.3 ± 0.7 Gy). ConclusionsAnatomical variations and prostate movements had more important dosimetric impact than anatomical variations alone, although, in some cases, the two phenomena compensated. Therefore, an efficient IGRT protocol is required for treatment implementation to reduce setup errors and control intrafraction motion.

HypoFocal SRT Trial: Ultra-hypofractionated focal salvage radiotherapy for isolated prostate bed recurrence after radical prostatectomy; single-arm phase II study; clinical trial protocol

IntroductionDespite radical prostatectomy (RP) and radiotherapy (RT) being established treatments for localised prostate cancer, a significant number of patients experience recurrent disease. While conventionally fractionated RT is still being used...

Safety of Ultrahypofractionated Pelvic Nodal Irradiation in the Definitive Management of Prostate Cancer: Systematic Review and Meta-analysis

Aim: This systematic review and meta-analysis aimed to evaluate the evidence for ultra-hypofractionated pelvic nodal irradiation in prostate cancer patients, with a focus on reported acute and late toxicities. Methods: A comprehensive search was conducted in five electronic databases (PubMed, Scopus, Web of Science, Cochrane Library, Clinicaltrials.gov) from inception until 23 March 2023. Eligible publications included patients with intermediate- and high-risk and node positive prostate cancer who underwent elective or therapeutic ultra-hypofractionated pelvic nodal irradiation. Primary outcomes included the presence of grade ≥2 rates of acute and late gastrointestinal and genitourinary toxicity based on the Common Terminology Criteria for Adverse Events (CTCAE) scale or Radiation Therapy Oncology Group (RTOG) scales. Quality assessment was performed using NIH tools for non-controlled before and after clinical trials, as well as single-arm observational studies. Since all outcomes were categorical variables, proportion was calculated to estimate the effect size and compare the outcomes after the intervention. Results: We identified 16 publications that reported the use of ultra-hypofractionated radiotherapy to treat the pelvis in prostate cancer. Seven publications met our criteria and were included in the meta-analysis, including 417 patients. The median total dose to the pelvic lymph nodes was 25 Gy (range: 25 - 28.5 Gy), with a median of 5 fractions. The prostate received a median dose of 40 Gy (range: 35 to 47.5 Gy). All studies utilized androgen deprivation therapy for a median duration of 18 months. The median follow-up period was 3 years (range: 0.5-5.6 years). The rates of acute grade ≥2 gastrointestinal and genitourinary toxicity were 8% (CI 95%: 1% to 15%) and 29% (CI 95%: 18% to 41%), respectively. For late grade ≥2 gastrointestinal and genitourinary toxicity, the rates were 13% (CI 95%: 5% to 21%) and 29% (CI 95%: 17% to 42%), respectively. Conclusion: Ultra-hypofractionated pelvic nodal irradiation appears to be a safe approach in terms of acute and late genitourinary and gastrointestinal toxicity.

Large scale experience of two ultrahypofractionated 5 fractions regimes after breast conserving surgery from a single centre

Purpose Ultra-hypofractionation breast radiotherapy is a safe alternative to moderate hypofractionation. This study reports the results of two ultrahypofractionated regimens used in clinical practice in a high-volume radiotherapy center in terms of efficacy and of tolerance. Methods we included all patients treated in an adjuvant setting with five fractions after breast conserving surgery (BCS), for a histologically-confirmed invasive or in situ breast carcinoma. Radiotherapy regimens after BCS were either a 5-week schedule with 5 weekly fractions of 5,7 Gy or a one-week schedule with 5 daily fractions of 5,2 Gy. Adverse events were recorded and local-relapse free survival (LRFS), locoregional-relapse free survival (LRRFS), metastasis-free survival (MFS), for breast-cancer specific survival (BCSS) and overall survival (OS) were evaluated. Results Between December 2014 and December 2022, 396 patients (400 breasts) were treated with ultrahypofractionated radiotherapy. Five-year LRFS was 98.8% (95% confidence interval: 97.1%–100%), and 5-year OS was 96.0% (95%CI: 92.6–99.5%). Age was statistically associated with OS in univariate analysis (HR: 1.16, 95%CI: 1.04–1.42, p = .01). Four patients (1.0%) experienced acute grade 3 radiation-induced adverse events, and 8 patients (2.3%) acute grade 2 toxicities. Twenty-three patients (5.8%) experienced late toxicity, all of them being graded as grade 1. The use of the 5.7 Gy-weekly-fraction regimen and the delivery of a tumor bed boost were significantly associated with acute radiodermatitis (p < .01; p = .02; respectively) and late fibrosis (p < .01; p = .049; respectively). Conclusions ultrahypofractionated radiotherapy was associated with an excellent tumor control rate in our ‘real-life’ cohort with low-risk breast cancer patients. However, delivery of a tumor bed boost and using weekly 5.7-Gy fractions were associated with an increased risk of acute and late cutaneous toxicities.

Long-Term Outcomes Following Fairly Brief Androgen Suppression and Stereotactic Radiation Therapy in High-Risk Prostate Cancer: Update from the FASTR/FASTR-2 Trials.

There has been emerging interest in the role of ultra-hypofractionated radiotherapy for high-risk prostate cancer, especially given its low α/β ratio. However, there is limited data on the long-term outcomes of this treatment strategy. The FASTR and FASTR-2 clinical trials were designed to assess the tolerability of stereotactic ablative body radiotherapy (SABR) in high-risk prostate cancer. FASTR was discontinued early due to unacceptable acute toxicity, whereas the acute toxicities in FASTR-2 were minimal. Herein, the long-term results from these trials are reported. Eligible patients had at least 1 high-risk feature as per the National Comprehensive Cancer Network criteria for high-risk prostate cancer, no evidence of metastatic disease, and either a score of 3+ on the Vulnerable Elderly Scale or declined standard therapy. A total of 19 patients from a single institution were enrolled on FASTR between 2011 and 2015. They received 40 Gy to the prostate and 25 Gy to the pelvic lymph nodes in 5 fractions delivered once weekly for 5 weeks, along with 1 year of androgen deprivation therapy (ADT). The excessive acute toxicity in FASTR prompted several modifications in FASTR-2, including the omission of nodal irradiation. A total of 30 patients from the same institution were enrolled on FASTR-2 between 2015 and 2017. They received 35 Gy to the prostate alone in 5 fractions delivered once weekly for 5 weeks, along with 18 months of ADT. A total of 44 patients were eligible for analysis, 16 from FASTR and 28 from FASTR-2. Most patients were >70 years old (77%). High-risk features included Gleason score ≥8 (46%), T3-T4 disease (27%) and baseline PSA >20 (50%). With a median follow-up of 6.4 years, the cumulative incidence of grade ≥3 genitourinary/gastrointestinal toxicity was 50% among FASTR patients and 7% among FASTR-2 patients. At 5 years, the combined rates of biochemical failure-free survival, freedom from distant metastases, prostate cancer-specific survival and overall survival were 72%, 90%, 92% and 83%, respectively. A total of 12 patients (27%) required further treatment. No significant differences in clinical outcomes were noted between the FASTR and FASTR-2 cohorts. SABR for high-risk prostate cancer is an attractive option for reducing treatment burden. Clinical outcomes and toxicity with the FASTR-2 protocol were comparable to conventionally-fractionated radiotherapy plus ADT. Larger prospective, randomized trials exploring the role of SABR with ADT in high-risk disease are necessary to better understand the efficacy and tolerability of this approach.

Interim Toxicity Analysis From the Randomized HERMES Trial of 2- and 5-Fraction Magnetic Resonance Imaging–Guided Adaptive Prostate Radiation Therapy

Ultrahypofractionated radiation therapy (UHRT) is an effective treatment for localized prostate cancer with an acceptable toxicity profile; boosting the visible intraprostatic tumor has been shown to improve biochemical disease-free survival with no significant effect on genitourinary (GU) and gastrointestinal (GI) toxicity. HERMES is a single-center noncomparative randomized phase 2 trial in men with intermediate or lower high risk prostate cancer. Patients were allocated (1:1) to 36.25 Gy in 5 fractions over 2 weeks or 24 Gy in 2 fractions over 8 days with an integrated boost to the magnetic resonance imaging (MRI) visible tumor of 27 Gy in 2 fractions. A minimization algorithm with a random element with risk group as a balancing factor was used for participant randomization. Treatment was delivered on the Unity MR-Linac (Elekta AB) with daily online adaption. The primary endpoint was acute GU Common Terminology Criteria for Adverse Events version 5.0 toxicity with the aim of excluding a doubling of the rate of acute grade 2+ GU toxicity seen in PACE. Analysis was by treatment received and included all participants who received at least 1 fraction of study treatment. This interim analysis was prespecified (stage 1 of a 2-stage Simon design) for when 10 participants in each treatment group had completed the acute toxicity monitoring period (12 weeks after radiation therapy). Acute grade 2 GU toxicity was reported in 1 (10%) patient in the 5-fraction group and 2 (20%) patients in the 2-fraction group. No grade 3+ GU toxicities were reported. At this interim analysis, the rate of GU toxicity in the 2-fraction and 5-fraction treatment groups was found to be below the prespecified threshold (5/10 grade 2+) and continuation of the study to complete recruitment of 23 participants per group was recommended.

Incidence, Radiologic and Dosimetric Parameters Associated with Radiation Induced Breast Lymphedema

Radiation induced breast lymphedema (BL) is an underreported but common finding. This study aimed to report the incidence of clinical BL and investigate the radiologic and dosimetric parameters associated with higher risk of BL. This IRB approved study included women with breast cancer who underwent breast conservative surgery followed by adjuvant radiation therapy between 2019 and 2021 at our institution. We reviewed the eligible patients' charts for incidence of clinical BL resulting in symptoms and requiring physical therapy referral. Thickness of the skin at defined center and bottom points of the breast was measured for patient' baseline and follow up mammograms. Dosimetric parameters were imported from patients' radiation plans including mean, maximum doses, and volumes receiving 20, 30, 40, & 50 Gy (V20, V30, V40, & V50), of the whole breast (WB), breast_eval (BE), and breast skin (BS) (defined as the superficial 5 mm of the skin). A chi-square test was used to test the association between clinical BL and radiation treatment regimens and beam energies and the association of skin thicknesses between those who had clinical BL and those who did not. A Wilcoxon rank sum test was used to test the association of the dosimetric parameters with clinical BL. We identified 268 patients who were eligible for the study. After chart and radiologic review, 119 patients had complete records available and were included in this study. Twenty-nine patients (24.4%) of the patients presented with symptomatic BL. Most patients (68%) received hypofractionated (42.56 Gy with or without 10 Gy boost), while 25% received conventional and 7% received ultra-hypofractionated radiotherapy. There was no association between the fractionation and incidence of BL (p = 0.4). There was no association between breast size and BL (mean 1065 cc vs 1232 cc, p = 0.35). There was significant association between BL and BS V30 (142cc vs 162 cc, p = 0.02), and BS V40 (82 cc vs 102 cc, p = 0.02), and a trend towards significant association with BS V20 (172cc vs. 193cc, p = 0.08), BS V50 (8 cc vs. 16 cc, p = 0.06). There was no significant association between BL and BS mean dose (36.9 Gy vs 39 Gy p = 0.11), or BS max dose (53.9 Gy vs 54.1 Gy, p = 0.21). None of the dosimetric parameters of WB and BE had significant association with clinical BL. Utilizing ROC analysis, there was significant association between clinical BL and the change of baseline mammogram breast skin thickness and skin thickness at 6 months follow up mammograms (+13 mm center point p = 0.04, +9 mm bottom point p<0.5), and at 12 months mammograms (+15 mm center point p<0.5, +11 mm bottom point p<0.5). Almost 1 in 4 women experienced radiation induced BL in our cohort. BS V30 & V40 are significantly associated with higher risk of BL. There was significant association between increased skin thickening in 6- and 12-months follow up mammograms and BL. Further analysis will follow to assess the association between surgical and clinical characteristics and BL.

Financial Implications of Evolving Breast Cancer Radiotherapy Treatment Protocols

Adjuvant radiotherapy for breast cancer represents a significant portion of radiotherapy (RT) treatments. The resource implications of evidence-based changes in treatment protocols must be defined to facilitate RT service planning. We designed a study to calculate the impact of past changes and create a model to allow prediction of costs implications for future changes. Changes in RT treatment (shown in table 1) in the past 3 years were identified in consultation with clinical staff and by reviewing institutional treatment guidelines. Resource and infrastructure costs were calculated for each protocol. Staff time was calculated using standard time slots where known (e.g., CT simulation appointment) and estimates based on discussion with staff (e.g., time to plan whole breast RT). Cost / Gy was calculated based on Linac cost of €2.5M, 10% annual service charge over 12-year lifetime, 2.7 patients treated / hour (verified institutional metric) and standard 2Gy fraction, giving €37.72 / Gy. We did not include facilities costs nor account for differing treatment outcomes. We collected relevant data on a consecutive 6-month sample (Jan - Jun 2019) of women receiving adjuvant RT for breast cancer (n = 224). Total costs were calculated by applying costs for each protocol change to the women in this cohort eligible for the changes. Protocol changes and costs are summarized in table 1. The use of DIBH for women <60 years receiving IMN RT (left and right sided) added a cost. The largest cost saving resulted from more selective tumor bed boost, a saving of €462,138. The potential impact of a 5-fraction boost for women with non-low risk DCIS was estimated. In the cohort analyzed, identified changes in adjuvant breast radiotherapy resulted in overall savings due to updated indications for boost and the implementation of ultra-hypofractionated radiotherapy. We are now analyzing the impact of introducing simultaneous integrated boost and partial breast radiotherapy.

MRI-Guided Radiation Therapy for Prostate Cancer: The Next Frontier in Ultrahypofractionation.

Technological advances in MRI-guided radiation therapy (MRIgRT) have improved real-time visualization of the prostate and its surrounding structures over CT-guided radiation therapy. Seminal studies have demonstrated safe dose escalation achieved through ultrahypofractionation with MRIgRT due to planning target volume (PTV) margin reduction and treatment gating. On-table adaptation with MRI-based technologies can also incorporate real-time changes in target shape and volume and can reduce high doses of radiation to sensitive surrounding structures that may move into the treatment field. Ongoing clinical trials seek to refine ultrahypofractionated radiotherapy treatments for prostate cancer using MRIgRT. Though these studies have the potential to demonstrate improved biochemical control and reduced side effects, limitations concerning patient treatment times and operational workflows may preclude wide adoption of this technology outside of centers of excellence. In this review, we discuss the advantages and limitations of MRIgRT for prostate cancer, as well as clinical trials testing the efficacy and toxicity of ultrafractionation in patients with localized or post-prostatectomy recurrent prostate cancer.

Stereotactic Body Radiation Therapy: A Radiosurgery Society Guide to the Treatment of Localized Prostate Cancer Illustrated by Challenging Cases

Traditionally, external beam radiotherapy (EBRT) for localized prostate cancer (PCa) involved lengthy courses with low daily doses. However, advancements in radiation delivery and a better understanding of prostate radiobiology have enabled the development of shorter courses of EBRT. Ultrahypofractionated radiotherapy, administering doses greater than 5 Gy per fraction, is now considered a standard of care regimen for localized PCa, particularly for intermediate-risk disease. Stereotactic body radiotherapy (SBRT), a specific type of ultrahypofractionated radiotherapy employing advanced planning, imaging, and treatment technology to deliver in five or fewer fractions, is gaining prominence as a cost-effective, convenient, and safe alternative to longer radiotherapy courses. It is crucial to address practical considerations related to patient selection, fractionation scheme, target delineation, and planning objectives. This is especially important in challenging clinical situations where clear evidence for guidance may be lacking. The Radiosurgery Society endorses this case-based guide with the aim of providing a practical framework for delivering SBRT to the intact prostate, exemplified by two case studies. The article will explore common SBRT dose/fractionation schemes and dose constraints for organs-at-risk. Additionally, it will review existing evidence and expert opinions on topics such as SBRT dose escalation, the use of rectal spacers, the role of androgen deprivation therapy in the context of SBRT, SBRT in special patient populations (e.g., high-risk disease, large prostate, high baseline urinary symptom burdens, and inflammatory bowel disease), as well as new imaging-guidance techniques like Magnetic Resonance Imaging for SBRT delivery.

Abstract P1-10-03: Ultra-hypofractionated Radiotherapy for Breast Cancer: A Brazilian Single-Institutional Series

Abstract INTRODUCTION Extreme hypofractionation in patients with early-stage breast cancer has been studied in randomized phase III non-inferiority trials. There is scarce data on this strategy in Latin American patients. OBJECTIVES To describe the profile of patients diagnosed with breast cancer treated with radiotherapy with an ultra-hypofractionated regimen (5 fractions of 5.2 Gy, in one week), as well as the dosimetric aspects and acute toxicity related to the treatment. METHOD Retrospective cohort through a Brazilian uni-institutional series, with analysis of pathological, dosimetric, and toxicity variables. RESULTS Between May 2020 and March 2022, 67 patients were included, with a median age at diagnosis of 71 years (41-93). Regarding staging, 25.8% had in situ tumors, 60.6% of patients were IA, and only 3% were stage IIA. Nineteen percent of patients had histological grade 3; 24.6%, had nuclear grade 3. Hormone receptors were positive in 92.1% of patients. The mean ki67 was 19%, and HER2 was negative at 84.5%. All patients underwent conservative surgery, and 5 underwent reconstruction with autologous flaps. Fifty-one patients underwent hormone therapy and only 2 underwent adjuvant chemotherapy. All but two patients were treated with the conformal technique (VMAT was used due to unfavorable anatomy). The mean volume of the irradiated breast was 926 cm3 (ranging from 920 to 932 cm3). Regarding the constraints of the organs at risk, the average V8Gy of the ipsilateral lung was 11.4%, ranging from 0 to 24%. In the heart, the average volumes receiving 1.5Gy and 7Gy were, respectively, 9.2% and 0.7%. No patient had acute toxicity greater than grade 2. The effects on the skin appeared on average 20 days after the end of treatment, with resolution in a maximum of 3 months. The median follow-up time was 10 months (3 - 26). We did not observe any case of local-recurrence, of breast-cancer-related death. CONCLUSION Although our follow-up time is premature, we have found that ultra-hypofractionated radiotherapy was feasible, tolerable, and safe, for patients with early breast cancer. Also, the constraints on the organs at risk were respected. There were no high-grade acute toxicities. Besides convenience, ultra-hypofractionation can improve access to radiotherapy in resource-scarce settings. Citation Format: Leticia Hernandes de Brito, Felipe Cicci Farinha Restini, Maria Thereza Mansur Starling, Gabriela Silva Moreira de Siqueira, Gustavo Nader Marta, Heloisa de Andrade Carvalho, Samir Abdallah Hanna. Ultra-hypofractionated Radiotherapy for Breast Cancer: A Brazilian Single-Institutional Series [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-03.

Assessment of delivered dose in prostate cancer patients treated with ultra-hypofractionated radiotherapy on 1.5-Tesla MR-Linac.

To quantitatively characterize the dosimetric effects of long on-couch time in prostate cancer patients treated with adaptive ultra-hypofractionated radiotherapy (UHF-RT) on 1.5-Tesla magnetic resonance (MR)-linac. Seventeen patients consecutively treated with UHF-RT on a 1.5-T MR-linac were recruited. A 36.25 Gy dose in five fractions was delivered every other day with a boost of 40 Gy to the whole prostate. We collected data for the following stages: pre-MR, position verification-MR (PV-MR) in the Adapt-To-Shape (ATS) workflow, and 3D-MR during the beam-on phase (Bn-MR) and at the end of RT (post-MR). The target and organ-at-risk contours in the PV-MR, Bn-MR, and post-MR stages were projected from the pre-MR data by deformable image registration and manually adapted by the physician, followed by dose recalculation for the ATS plan. Overall, 290 MR scans were collected (85 pre-MR, 85 PV-MR, 49 Bn-MR and 71 post-MR scans). With a median on-couch time of 49 minutes, the mean planning target volume (PTV)-V95% of all scans was 97.83 ± 0.13%. The corresponding mean clinical target volume (CTV)-V100% was 99.93 ± 0.30%, 99.32 ± 1.20%, 98.59 ± 1.84%, and 98.69 ± 1.85%. With excellent prostate-V100% dose coverage, the main reason for lower CTV-V100% was slight underdosing of seminal vesicles (SVs). The median V29 Gy change in the rectal wall was -1% (-20%-17%). The V29 Gy of the rectal wall increased by >15% was observed in one scan. A slight increase in the high dose of bladder wall was noted due to gradual bladder growth during the workflow. This 3D-MR-based dosimetry analysis demonstrated clinically acceptable estimated dose coverage of target volumes during the beam-on period with adaptive ATS workflow on 1.5-T MR-linac, albeit with a relatively long on-couch time. The 3-mm CTV-PTV margin was adequate for prostate irradiation but occasionally insufficient for SVs. More attention should be paid to restricting high-dose RT to the rectal wall when optimizing the ATS plan.

Cost-effectiveness analysis of ultra-hypofractionated radiotherapy and conventionally fractionated radiotherapy for intermediate- to high-risk localized prostate cancer.

Radiotherapy is an effective curative treatment option for intermediate- to high-risk localized prostate cancer. According to the HYPO-RT-PC trial (ISRCTN45905321), there was no significant difference in 5 years of follow-up in terms of failure-free survival, overall survival, urinary toxicity, and bowel toxicity, while erectile function decreased between ultra-hypofractionated radiotherapy with conventionally fractionated radiotherapy, except that the incidence of urinary toxicity in ultra-hypofractionated radiotherapy was higher at 1 year of follow-up. We evaluated the cost-effectiveness of ultra-hypofractionated radiotherapy and conventionally fractionated radiotherapy for intermediate- to high-risk localized prostate cancer from the Chinese payer's perspective. We developed a Markov model with a 15-year time horizon to compare the cost and effectiveness of ultra-hypofractionated radiotherapy with those of conventionally fractionated radiotherapy for localized intermediate- to high-risk prostate cancer. The outcomes were measured in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and willingness-to-pay (WTP). Univariable and probability sensitivity analyses were performed to evaluate the robustness of the Markov model. Based on the Markov model, conventionally fractionated radiotherapy yielded 2.32 QALYs compared with 2.14 QALYs in ultra-hypofractionated radiotherapy in China. The cost of ultra-hypofractionated radiotherapy was found to be decreased by about 14% folds ($4,251.04) in comparison with that of conventionally fractionated radiotherapy. The ICER of conventionally fractionated radiotherapy versus that of ultra-hypofractionated radiotherapy was $23,616.89 per QALY in China. The failure-free survival with grade 2 or worse urinary toxicity and the discount rate per annum were the most sensitive parameters utilized in ultra-hypofractionated radiotherapy. The cost-effectiveness acceptability curve showed that conventionally fractionated radiotherapy had 57.7% probability of being cost-effective under the Chinese WTP threshold. From the perspective of Chinese payers, ultra-hypofractionated radiotherapy was not a cost-effective strategy compared with conventionally fractionated radiotherapy for patients with localized intermediate- to high-risk prostate cancer. Nevertheless, reduction of the grade 2 or worse urinary toxicity of ultra-hypofractionated radiotherapy could alter the results.

Prostate Cancer: Management of Biochemical Recurrence after Surgery.

Radical prostatectomy (RP) is one of the primary treatment options for localised prostate cancer (PCa). Despite its curative intent, 1/3 of patients will experience biochemical recurrence (BCR) during follow-up. Experts have devoted efforts to associate the influence of each individual factor with the risk of BCR to select the optimal treatment for each patient. Optimal management must aim to find a balance between delaying the onset of metastatic disease and overtreating an indolent disease with treatments that can affect quality of life of the patients. Thus far, effective treatment options for men with BCR remain controversial in terms of ideal treatment timing (adjuvant vs. salvage), radiotherapy (RT) fields and doses, selection and duration of systemic therapy and potential synergies between treatments and their therapeutic sequencing. Next-generation imaging techniques, such as Prostate-Specific Membrane Antigen Positron Emission Tomography, are used for early detection of disease progression and exact site of recurrence or progression, thereby enhancing decision making for future disease management. In this review, we evaluate available evidence of controversial topics regarding BCR after RP and explore future directions, such as prognostic and/or predictive factors of response, genetic panels, second-generation hormone treatments, ultra-hypofractionated RT and ongoing clinical trials in this clinical scenario.

PP150 The Role Of Expert Consensus In UK Guidance: Patient Selection For Hydrogel Spacer Use During Prostate Cancer Radiotherapy

IntroductionIn UK males, prostate cancer is the most common cancer, with over 47,500 diagnosed annually. Radiotherapy is a highly effective curative treatment but can be limited by dose to surrounding normal-tissues such as the rectum. Radiation to the rectum can be reduced by increasing the distance between prostate and rectum with a hydrogel spacer. Despite National Institute of Health and Care Excellence guidance, spacers are not widely funded in the UK. Limited funding has necessitated patient prioritization, without any existing consensus on method.Studies have shown generally homogenous results in reduction of rectal toxicity across assessed subgroups, but the requirement to prioritize remains. One way of addressing the appropriate use of beneficial health technologies is the inclusion of end-user experts in decision-making. The study aim was to identify consensus among radiation oncologists on patient prioritization for rectal hydrogel spacers.MethodsWe conducted a Delphi study where six leading clinical oncologists and one urologist from across the UK experienced in using rectal hydrogel spacers participated in two rounds of online questionnaires and two virtual advisory board meetings.ResultsThe experts estimated that 83 percent of patients who could potentially benefit from a spacer were denied access. Overall, ten points of consensus were reached. Key ones concerning patient-access were:•Spacer use in eligible patients significantly reduces radiation dose to the rectum and toxicity-related adverse events.•Increased benefit is expected in patients on anticoagulation, with diabetes and with inflammatory bowel disease.•Increased benefit can be expected with ultra-hypofractionated radiotherapy, but radiotherapy modality is not a key consideration for patient selection.•Patients should have the opportunity to actively participate in the discussion regarding the use of a spacer.ConclusionsCurrently, not all patients who would benefit can access funding for hydrogel spacers. Consensus in this study indicates that appropriate health policy and funding mechanisms are warranted for patients, to provide equitable access to technologies improving quality of life.

Acute Toxicity and Quality of Life in a Post-Prostatectomy Ablative Radiation Therapy (POPART) Multicentric Trial

The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). Patients with post-radical prostatectomy PSA levels of ≥0.1-2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD21.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. From April 2021 to June 2022, thirty men with a median age of 72 years (range 55-82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18-1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0-0.48 ng/mL). Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy.

Early Institutional Experience of Ultra-Hypofractionated Breast Radiotherapy in a Large Academic Cancer Center

<h3>Purpose/Objective(s)</h3> Ultra-hypofractionated radiotherapy (U-HFRT) is non-inferior to moderate hypofractionation (M-HFRT) for local control following breast-conserving surgery for early-stage breast cancer and is safe in terms of normal tissue toxicity. Our objective was to evaluate early institutional experience of U-HFRT in a real-world setting at a large academic cancer center. <h3>Materials/Methods</h3> Stage 0-II breast cancer patients who received adjuvant whole breast irradiation (WBI) or partial breast irradiation (PBI) between May 2020 and March 2021 were compiled. Patients were divided into 2 cohorts: U-HFRT (26 Gy in 5 daily fractions) and M-HFRT (40.05 Gy in 15 fractions). Clinical and treatment characteristics were extracted from medical records and displayed using descriptive statistics. Physician-assessed skin toxicity was collected for patients treated with U-HFRT during RT and at follow-up visits using the RTOG radiation morbidity scale. Associations between toxicity and clinical/treatment characteristics were determined using mixed effects logistic regression, accounting for time. Comparisons between the U-HFRT and M-HFRT cohorts were performed using the Wilcoxon rank sum test (continuous) and Chi-square/Fisher's exact test (categorical). <h3>Results</h3> Median age at diagnosis for the entire cohort was 60.5 years: U-HFRT 66.2 years and M-HFRT 55.1 years (p<0.001). For the U-HFRT cohort, 70% had hormone-receptor positive invasive breast cancer (70% pT1c, 95% pN0) and 20% had DCIS. WBI/PBI was delivered to 385 patients, of which 188 (49%) received U-HFRT. For these patients, the majority (72%) received WBI, 28% PBI and a boost was used in 26%, compared to 96%, 4% and 47%, respectively, for those treated with M-HFRT (p<0.001). Grade 1 RTOG skin toxicity significantly improved over time for patients who received U-HFRT: 37% during RT, 57% within 90 days post-RT and 6% >1-year post-RT (p<0.001). Grade 2 toxicity was minimal (5% within 90 days post-RT) and there were no grade 3 toxicities. Age, RT volume (WBI vs. PBI) and chemotherapy were not associated with toxicity for U-HFRT; however, increased toxicity was observed for patients who received a boost (p<0.001). Factors associated with increased usage of U-HFRT were older age, use of PBI, no boost and no breast reconstruction (p<0.001). <h3>Conclusion</h3> U-HFRT was rapidly adopted at our institution for early-stage breast cancer and is associated with low rates of reported skin toxicity. The use of U-HFRT was greatest in patients with low-risk breast cancer, consistent with a conservative approach to implementation in a real-world setting.