Ultrahypofractionated Radiation Therapy Research Articles

Abstract PO5-22-05: ULTRA-HYPOFRACTIONATED ADJUVANT RADIATION THERAPY FOR BREAST CANCER (UK FAST FORWARD TRIAL): A REAL LIFE SCENARIO ANALYSIS IN A DEVELOPING COUNTRY

Abstract Introduction: Selected patients showed non-inferior outcomes after conservative surgery for early breast cancer in the FAST-Forward UK (26Gy in 5 fractions) when compared to standard to date treatment. This study triggered an important change in radiation therapy routines across the world. We aimed to establish a pattern of treatment related events at a third-world country cancer center. Methods: We retrospectively analyzed all patients treated with 26Gy in 5 fractions (1 week) from January 2020 to June 2023. All data was exported and analyzed for demographics. A clinical profile was traced, dosimetric parameters and side effects assessed based on individual inquiries to each patient, per and post treatment. A strict medical record was kept in order to understand patterns of side effects and results. Results: 101 individuals were identified. Mean age was 64 years, 48 (47%) patients experienced radiation dermatitis of any grade, 33 (32%) grade 1, 9 (8%) grade 2, 6 grade 3 or 4 (5%). Patients older than 60 years showed to be a significant factor for dermatitis development (34 over a total of 48 - 70%) and 8 (53%) over 15 had grade 2 or higher dermatitis. 27 (26%) developed radiation dermatitis during sessions. 21 (20%) took 7 or less days to heal; 27 (26%) had a recovery longer than one week at an average age of 65 years - being the majority of dermatitis grade 1. Reported toxicities were sharp pain 31 (30%), burning pain 24 (23%), edema 17 (16%) and pruritus 5 (4%). At the time of this study was completed, 3 reported deaths (2%) were reported - with a 97% rate of survival. Conclusions: The fast forward trial regimen has 3 years since its publication. Our study shows that in a selected group of breast cancer patients, this novel model has shown to be a safe alternative for adjuvant radiation therapy following breast conservative surgery, results corroborating with published data. To the best of our knowledge, this is the largest single center group analyzed and published. Citation Format: Renne Bart, Daniel Przybysz, Ramon Ferrari, Leonardo Franco, Carlos Almeida, Paulo Canary. ULTRA-HYPOFRACTIONATED ADJUVANT RADIATION THERAPY FOR BREAST CANCER (UK FAST FORWARD TRIAL): A REAL LIFE SCENARIO ANALYSIS IN A DEVELOPING COUNTRY [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-22-05.

Ultrahypofractionated Radiation Therapy for Prostate Cancer Including Seminal Vesicles in the Target Volume: A Treatment-planning Study Based on the HYPO-RT-PC Fractionation Schedule

PurposeUltra-hypofractionated (UHF) radiation therapy (RT) has become a treatment alternative for patients with localized prostate cancer. In more advanced cases, seminal vesicles (SV) are routinely included in the target volume. The Scandinavian HYPO-RT-PC trial, which compared 42.7Gy in 7 fractions (fr) to conventional fractionation (CF), did not include SV in the CTV. The primary objective of the present work is to implement a UHF simultaneous integrated boost (SIB) for prostate cancer RT, incorporating SV into the target volume based on this fractionation schedule. A secondary objective is to analyze the unintentional dose coverage of SV from state-of-the-art VMAT treatments to the prostate gland only. Material and MethodsTwo different equi-effective UHF-SIB treatment schedules to SV were derived based on the CF clinical schedule (50.0Gy/25fr to elective SV and 70.0Gy/35fr to verified SV-invasion (SVI)) using the linear quadric model with α/β=2Gy and 3Gy. The dose to the prostate was 42.7Gy/7fr in both schedules with 31.2Gy/37.8Gy (α/β=2Gy) and 32.7Gy/40.1Gy (α/β=3Gy) to elective SV/verified SVI. VMAT plans to the proximal 10mm and 20mm were optimized and dose-volume-metrics for target volumes and organs at risk (OAR) evaluated. ResultsDose metrics were overall lower for UHF-SIB compared to CF. QUANTEC based volume-criteria are 2-7% lower for rectum and 2-4% lower for bladder in the UHF-SIB. D98% to elective SV were 7-12Gy3 lower with UHF-SIB and the corresponding data for verified SVI were about 2-3Gy3. The SV(10mm) V90%/(29.5Gy) for prostate only treatments (42.7Gy) were in median (IQR) 99% (87-100)/ 78% (58-99) for CTV/PTV. ConclusionUHF RT, based on the HYPO-RT-PC fractionation schedule, with a SIB technique to the prostate and the base of the SV can be planned with lower doses (EQD2) to OARs compared to CF. Unintentional dose to the proximal parts of SV in prostate only treatment can be substantial.

Changes in Radiation Therapy: New Ultrahypofractionated Radiation, Repeat Breast Conservation Therapy in the Management of Breast Recurrence with Re-irradiation, Proton Therapy

Changes in Radiation Therapy: New Ultrahypofractionated Radiation, Repeat Breast Conservation Therapy in the Management of Breast Recurrence with Re-irradiation, Proton Therapy

Ultra-Hypofractionated Involved Site Radiation Therapy (ISRT) As Salvage or Bridging Therapy in Aggressive Non-Hodgkin Lymphomas

Introduction: Conventional fractionated radiation treatment (RT) to a total dose of 40-50 Gy in 20-25 fractions is typically recommended in the ‘definitive’ intent treatment of aggressive chemorefractory non-Hodgkin lymphoma. However, during the time of COVID-19, recommendations for hypofractionated courses (5-13 fractions) arose (Yahalom et al Blood 2020) as modern radiation techniques should allow similar total doses to be delivered safely in far fewer fractions. Our aim is to evaluate the outcomes and toxicities of ultra-hypofractionated (</=5 fractions) ‘definitive’ ISRT in aggressive non-Hodgkin lymphomas to see if this may be an acceptable alternate recommendation beyond COVID-19. Methods: We conducted an IRB-approved, retrospective review of all aggressive non-Hodgkin lymphoma patients treated at our institution with ‘definitive’ intent (40-50 Gy EQD2 with an α/β of 10) ultra-hypofractionated ISRT between April 2020 and July 2023. Demographic, disease-specific, and treatment-related variables were collected. Primary outcomes include objective response rate (ORR), defined as complete (CR) or partial response (PR) on post-RT positron emission tomography (PET) scans using the Lugano classification, local failure (LF), and radiation-related toxicity per CTCAE v5. Secondary outcomes include overall disease control and survival. Results: 26 ultra-hypofractionated radiation treatments were identified from 23 unique patients who were treated with ‘definitive’ intent ISRT (39.1% salvage, 30.4% early-salvage post CAR-T, and 30.4% bridging to SCT or CAR-T). The most common dose was 30 Gy in 5 fractions (96%); all patients were treated with IMRT with SBRT-type immobilization and image guidance as clinically indicated. The most common diagnosis was DLBCL (91%). 10/23 (43%) patients were female, the majority (82%) were ECOG 0-1 performance status, and the average age at time of RT was 68.9 years. 39% had all FDG-avid sites at the time of radiation treated. The median follow-up was 8.3 months (range 0.3-27.9 months). 26% of patients had acute radiation related toxicities, which were all grade 1-2 with the most common being fatigue (30%). There were no grade 3-4 toxicities, and no subacute or long-term toxicities. Initial local ORR was 20/21, or 95% (86% CR and 10% PR), while initial overall ORR was 12/21, or 57% (52% CR and 5% PR). At time of last follow up, only 1/24 (4%) of irradiated sites had local failure (2 data points N/A), with a TTLF of 1.5 months. 62% of patients had disease progression, with median time to disease progression of 1.5 months. At time of last follow up, 48% were dead, with a median time to death of 6.6 months. Conclusions: Ultra-hypofractionated ISRT in the ‘definitive’ intent treatment of aggressive non-Hodgkin lymphomas has excellent local tumor control and appears to be safe with minimal acute and subacute toxicities. In addition to patient convenience and cost effectiveness, short-course ISRT allows patients to quickly move on to next-line therapy when indicated. Prospective studies and long-term follow up are needed to further validate this as an alternative radiation treatment option.

Late Toxicity of Prostate Ultrahypofractionated Radiation Therapy Compared With Moderate Hypofractionation in a Randomized Trial

PurposeWe report late toxicity, quality of life (QOL) and urinary symptom score with prostate cancer radiotherapy in a randomized trial comparing moderate hypofractionation (MHF) and ultrahypofrationation (UHF) Methods and MaterialsPatients with intermediate and high risk prostate cancer were randomized to either Arm 1 (70Gy/28 fractions) or Arm 2 (36.25Gy/5 weekly fractions). Late toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) and Radiation Therapy Oncology Group/Subjective, Objective, Management, Analytic (RTOG/SOMA) scales. QOL was assessed with the Expanded Prostate Inventory Composite-26 Short Form (EPIC-26) and urinary function with the International Prostate Symptom Score (IPSS). ResultsEighty participants were randomized. Two from Arm 1 withdrew, leaving 36 patients in Arm 1 and 42 in Arm 2. There were no significant differences in baseline characteristics, except for worse IPSS in Arm 2. No difference was observed in freedom from grade 3 or worse toxicity between treatments (p=0.921), with only a single grade 3 event in each arm. There was no significant difference in freedom from grade 2 or worse toxicity (p=0.280). No difference was observed in freedom from grade 2 or worse genitorurinary toxicity, with cumulative probabilities of 69.0% and 87.0% at 5-years for Arms 1 and 2, respectively (0.132). No difference was observed in freedom from grade 2 or worse gastrointestinal toxicity, with cumulative probabilities of 74.0% in Arm 1 and 80.0% in Arm 2 (p=0.430). There were no significant differences in EPIC-26 QOL between arms. ConclusionUHF, delivered weekly, is well tolerated with no significant differences in freedom from late toxicity compared to MHF.

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 is limited data on the long-term outcomes of ultrahypofractionated radiation therapy in high-risk prostate cancer. The FASTR and FASTR-2 trials were designed to assess the tolerability of stereotactic ablative radiation therapy (SABR) in this context. Herein, the long-term results are reported. Eligible patients had localized high-risk prostate cancer and were either ≥70 years old, had a score of ≥3 on the Vulnerable Elderly Scale, or declined standard therapy. Nineteen 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 weekly fractions, with 12 months of androgen deprivation therapy (ADT). Thirty patients from the same institution were enrolled on FASTR-2 between 2015 and 2017. They received 35 Gy to the prostate alone in 5 weekly fractions, with 18 months of ADT. Updated toxicity and outcomes were assessed retrospectively. Kaplan-Meier estimates were calculated for biochemical failure-free survival, freedom from distant metastases, prostate cancer-specific survival, and overall survival. Forty-four patients were eligible for analysis, 16 from FASTR and 28 from FASTR-2. Thirty-four patients (77%) were >70 years old. High-risk features included Gleason score ≥8 (n=20, 46%), T3-T4 disease (n=12, 27%), and baseline prostate-specific antigen > 20 (n=22, 50%). Median follow-up was 6.4 years. The 5-year cumulative incidence of late grade ≥3 genitourinary/gastrointestinal toxicity was 32% in FASTR and 11% in FASTR-2. 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. SABR can be safely delivered in high-risk prostate cancer by optimizing technical delivery, particularly with adherence to strict dose constraints for organs at risk. The clinical outcomes in FASTR and FASTR-2 were largely comparable to more standard fractionation schemes plus ADT, but further modifications may improve disease control. Larger randomized trials are necessary to better understand the efficacy and tolerability of this approach.

Favorable Toxicity and Local Control with Ultrahypofractionated Radiation Therapy (UH-RT) for Melanoma of the Lower Genital Tract (LGT)

To report our experience using UH-RT +/- immunotherapy (IO) in women with melanoma of the LGT. We retrospectively identified 23 patients who received UH-RT to primary tumor for vulvovaginal melanoma from 2012 to 2022. Median age was 69 years (IQR: 62-76). Stage included localized, node positive, or metastatic. 18 (78%) had tumors involving the vagina/cervix and 5 (22%) had vulvar tumors. 6 patients had c-KIT mutations; 13 patients were wild-type; 4 patients were unknown. 12 (52%) were treated at initial presentation (cohort A) and 11 (48%) at local progression/recurrence following prior therapy (cohort B). In cohort A, most (n = 11) received concurrent IO. In cohort B, 3 recurred after surgery alone, 4 after systemic therapy alone and 4 after surgery and systemic therapy. RT consisted of 6 Gy x 6 (n = 11), 6 Gy x 5 (n = 10) and 5 Gy x 5-6 (n = 2) delivered to the primary tumor + 0.5 cm margin. Patients initiated IO either ≥3 months preRT (n = 8), concurrent with RT (n = 12) or ≥3 months following RT (n = 2). 1 patient in cohort B did not receive IO. Toxicity was graded using CTCAE v 5. Overall survival (OS) was measured from end of RT. Cumulative incidence of local progression was measured from end of RT. Kaplan-Meier method and Cox regression were used for survival analyses. Landmark method was used for timing of IO. Median follow-up as determined by reverse Kaplan-Meier method was 60 months (95% CI: 37-N/A). Overall incidence of acute/late grade 2+ toxicity for the entire cohort was 34%. Grade 2 acute toxicity included: dermatitis (n = 3), urinary (n = 2), vaginitis (n = 2) and diarrhea (n = 1). 3 patients experienced grade 3 acute dermatitis. 1 patient experienced late grade 2 vaginitis. No grade 3 or 4 toxicity was noted. No significant differences in toxicity were noted between RT regimens. Local disease control was achieved in 61% of patients. Local only, local and distant, and distant-only progression were seen in 17%, 22%, and 30% of patients respectively. 2-year cumulative incidence of local progression was 33% for the whole cohort, 28% for cohort A, and 36% for cohort B (p = 0.4). On UVA, factors associated with local progression were vulvar disease (p = 0.02) and c-KIT mutation (p = 0.011). No significant difference in local control was noted based on biologic effective dose (BED10 < = 48Gy vs >48Gy) (p = 0.06). Median OS for entire cohort, cohort A, and cohort B were 46, 72, and 30 months, respectively. 2-year survival (95% CI) was 67% (50%-91%), 73% (51%-100%), and 64% (41%-99%) respectively. On UVA, non-local disease at time of RT (p = 0.016) and receipt of IO ≥3 months prior to RT (p = 0.030) had worse OS. UH-RT+/- IO for melanoma of the LGT is well-tolerated with local disease control achieved in 61% of patients. Vulvar primary and c-Kit mutations were associated with worse local control. Additional follow-up may be necessary to determine the value of dose escalation.

Dosimetric Analysis of Major Wound Complications Following Preoperative Ultra-Hypofractionated Radiation Therapy for Soft Tissue Sarcoma

Preoperative radiation therapy (RT) for soft tissue sarcomas (STS), delivered with conventional fractionation, has been shown to reduce long-term toxicity at the expense of increased postoperative major wound complications (MWC). Ultra-hypofractionated RT has emerged as a potential alternative preoperative modality with early but comparable outcomes to conventional regimens. However, limited data are available evaluating dosimetric, patient, and treatment specific factors associated with development of MWC in this setting. This IRB approved review included STS patients treated with preoperative 5 fraction daily RT followed by surgical resection within 7 days. Patients were evaluated for MWCs in association with patient and tumor characteristics, dosimetric parameters, and treatment techniques. MWCs were defined as a return to operating room, readmission for wound care or IV antibiotics, and persistent deep packing for >120 days. Prescription isodose line, PTV mean dose and the PTV volume exposed to 105% and 110% of prescribed dose were recorded. Dose to tissue likely to be involved in wound healing was assessed by creating a 1 cm thick superficial skin strip within 2 cm of the PTV which was then evaluated for volume, mean dose, V15, V21, V27, and V30. Secondary endpoints were locoregional control (LRC), metastasis free survival (MFS), and overall survival (OS). A total of 31 patients with a median age of 66 years (range 28-87) and a median follow up of 21 months (IQR 8-43) were included. All patients received 30 Gy in 5 fractions using IMRT/VMAT. There were 11 upper limb (36%) and 20 lower limb (65%) tumors included. Median time to resection following RT was 1 day (IQR 0-3). Median tumor size was 8 cm (IQR 5-13). MWC occurred in 13 patients (42%) with 10 patients (32%) requiring additional surgery. Dehiscence and infection requiring IV antibiotics occurred in 12 (39%) and 6 patients (19%), respectively. RT plans were predominately prescribed to the PTV mean (87%) with a median prescription isodose of 97% (IQR 96-97) and PTV mean dose of 3110 cGy (IQR 3089-3142). Median PTV volume, mean dose, and volume of PTV receiving 105% and 110% of the prescribed dose were higher in the MWC cohort although none reached significance. Similarly, for the 1 cm skin strip the median volume, mean dose, V30, V27, V21, and V15 were all higher in the MWC cohort without significant difference. Among patient, treatment, and tumor factors: tumor size, location, grade, margin status, type of wound closure, and prior non-oncologic resection were not associated with MWC. LRC, MFS, and OS at 3-years were 96%, 67%, and 76%, respectively. Although not reaching significance, increased plan homogeneity and reduced dose/volume relationships in proximity to the skin trended to reduced MWC in this limited cohort. Multi-institutional collaboration may be warranted to better identify factors associated with MWC in patients treated with preoperative ultra-hypofractionated RT.

Noninvasive inter- and intrafractional motion control in ultrahypofractionated radiation therapy of prostate cancer using RayPilot HypoCath™—a substitute for gold fiducial-based IGRT?

PurposeIn ultrahypofractionated radiation concepts, managing of intrafractional motion is mandatory because tighter margins are used and random errors resulting from prostate movement are not averaged out over a large number of fractions. Noninvasive live monitoring of prostate movement is a desirable asset for LINAC-based prostate stereotactic body radiation therapy (SBRT).MethodsWe prospectively analyzed a novel live tracking device (RayPilot HypoCath™; Micropos Medical AB, Gothenburg, Sweden) where a transmitter is noninvasively positioned in the prostatic urethra using a Foley catheter in 12 patients undergoing ultrahypofractionated intensity-modulated radiation therapy (IMRT) of the prostate. Gold fiducials (Innovative Technology Völp, Innsbruck, Austria) were implanted to allow comparison of accuracy and positional stability of the HypoCath system and its ability to be used as a standalone IGRT method. Spatial stability of the transponder was assessed by analyzing transmitter movement in relation to gold markers (GM) in superimposed kV image pairs. Inter- and intrafractional prostate movement and the impact of its correction were analyzed.ResultsA total of 64 fractions were analyzed. The average resulting deviation vector compared to the GM-based position was 1.2 mm and 0.7 mm for inter- and intrafractional motion, respectively. The mean intrafractional displacement vector of the prostate was 1.9 mm. Table readjustment due to exceeding the threshold of 3 mm was required in 18.8% of fractions. Repositioning reduced the time spent outside the 3‑mm margin from 7.9% to 3.8% of beam-on time. However, for individual patients, the time spent outside the 3‑mm margin was reduced from to 49% to 19%.Conclusionthe HypoCath system allows highly accurate and robust intrafractional motion monitoring. In conjunction with cone beam CT (CBCT) for initial patient setup, it could be used as a standalone image-guided radiation therapy (IGRT) system.

Current evidence for moderate and ultra-hypofractionated radiation therapy in prostate cancer: a summary of the results from phase 3 randomised trials.

A low α/β ratio for prostate cancer (PCa) compared to surrounding normal tissue theoretically implies therapeutical advantages with hypofractionated treatment. Data from large randomised control trials (RCTs) comparing moderate hypofractionated (MHRT, 2.4-3.4 Gray/fraction (Gy/fx)) and ultra-hypofractionated (UHRT, >5 Gy/fx) with conventionally fractionated radiation therapy (CFRT, 1.8-2 Gy/fx) and the possible clinical implications have been reviewed. We searched PubMed, Cochrane and Scopus for RCT comparing MHRT/UHRT with CFRT treatment of locally and/or locally advanced (N0M0) PCa. We found six RCTs, which compared different radiation therapy regimes. Tumour control and acute and late toxicities are reported. MHRT was non-inferior to CFRT for intermediate-risk PCa, non-inferior for low-risk PCa and not superior in terms of tumour control for high-risk PCa. Acute toxicity rates were increased compared to CFRT, especially an increase in acute gastrointestinal adverse effects was seen. Late toxicity related to MHRT seems to be comparable. UHRT was non-inferior in terms of tumour control in one RCT, with increased acute toxicity, but with comparable late toxicity. One trial, however, indicated increased late toxicity rates with UHRT. MHRT delivers similar therapeutic outcomes compared to CFRT in terms of tumour control and late toxicity for intermediate-risk PCa patients. Slightly more acute transient toxicity could be tolerated in favour of a shorter treatment course. UHRT should be regarded as an optional treatment for patients with low- and intermediate-risk disease applied at experienced centres in concordance with international and national guidelines.

A Multi-Institutional Phase 2 Trial of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer

Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART. One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%. The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy.

PO-1285 Post pandemic ultra-hypofractionated radiation in breast cancer from a tertiary Institution in India

PO-1285 Post pandemic ultra-hypofractionated radiation in breast cancer from a tertiary Institution in India

PO-1087 Use of breast cancer ultra-hypofractionated radiation treatments during and post COVID19 pandemic

PO-1087 Use of breast cancer ultra-hypofractionated radiation treatments during and post COVID19 pandemic

Treatment planning comparison of high-dose-rate brachytherapy vs. robotic and conventional stereotactic body radiotherapy for ultrahypofractionated treatment of prostate cancer.

Ultrahypofractionated radiation therapy is increasingly used in the treatment of prostate cancer. High-dose-rate brachytherapy (HDR-BT) and stereotactic body radiotherapy (SBRT) are representative methods of ultrahypofractionation. This study was performed to compare clinically applied treatment plans for patients who had been treated using HDR-BT vs. conventional or robotic SBRT. Calculated dose-volume indices between HDR-BT without a perirectal spacer (n=20), robotic SBRT without a spacer (n=40), and conventional (non-robotic) SBRT with a spacer (n=40) were compared. Percentages against the prescription dose regarding the planning target volume (PTV), bladder, rectum, and urethra were statistically compared. The D50% of the PTV with HDR-BT (140.5%±4.9%) was significantly higher than that with robotic or conventional SBRT (116.2%±1.6%, 101.0%±0.4%, p<0.01). The D2cm3 of the bladder with HDR-BT (65.6%±6.4%) was significantly lower than those with SBRT (105.3%±2.9%, 98.0%±1.3%, p<0.01). The D2cm3 of the rectum with HDR-BT (60.6%±6.2%) was also significantly lower than those with SBRT (85.1%±8.8%, 70.4%±9.6%, p<0.01). By contrast, the D0.1cm3 of the urethra with HDR-BT (117.1%±3.6%) was significantly higher than those with SBRT (100.2%±0.7%, 104.5%±0.6%, p<0.01). HDR-BT could administer a higher dose to the PTV and a lower dose to the bladder and rectum, at the cost of a slightly higher dose to the urethra compared with SBRT.

Alleviating Morbidity From Locally Advanced Breast Cancer Using a Practical and Short Radiation Therapy Regimen: Results of the HYPORT Palliative Studies

Locally advanced breast cancers lead to debilitating local symptoms. Treatment of these women encountered commonly in less resourced countries is not backed by strong evidence. We formulated the HYPORT and HYPORT B phase 1/2 studies to evaluate the safety and efficacy of hypofractionated palliative breast radiation therapy. Two studies (35 Gy/10 fractions; HYPORT ) and (26 Gy to breast/32 Gy tumor boost in 5 fractions; HYPORT B) were designed with increasing hypofractionation to save overall treatment time from 10 to 5 days. We report the acute toxicity, symptomatic, metabolic response, and quality of life (QOL) changes after radiation therapy. Fifty-eight patients, the majority of whom were pretreated with systemic therapy, completed the treatment. No grade 3 toxicity was reported. Response assessment at 3 months showed improvement in ulceration (58% vs 22%, P=.013) and bleeding (22% vs 0%, P=.074) within the HYPORT study. Similarly, in the HYPORT B study, ulceration (64% and 39%, P=.2), fungating (26% and 0%, P=.041), bleeding (26% and 4.3%, P=.074), and discharge (57% and 8.7%, P=.003) was reduced. Metabolic response was noted in 90% and 83% of patients, respectively, in the 2 studies. Improvement in the QOL scores were evident in both studies. Only 10% of the patients relapsed locally within 1 year. Palliative ultrahypofractionated radiation therapy to the breast is well tolerated, is effective, and results in a durable response with improved QOL. This could be considered a standard for locoregional symptom control.

Comparison of four-year toxicities and local control of ultra-hypofractionated vs moderate-hypofractionated image guided prostate radiation with HDR brachytherapy boost: A phase I-II single institution trial

Purpose/Objective(s)To analyze the long term efficacy and safety of an ultra-hypofractionated (UHF) radiation therapy prostate treatment regimen with HDR brachytherapy boost (BB) and compare it to moderate-hypofractionated regimens (MHF). Materials/MethodsIn this single arm, prospective monocentric study, 28 patients with intermediate risk prostate cancer were recruited in an experimental treatment arm of 25 Gy in 5 fractions plus a 15 Gy HDR BB. They were then compared to two historical control groups, treated with either 36 Gy in 12 fractions or 37.5 Gy in 15 fractions with a similar HDR BB. The control groups included 151 and 311 patients respectively. Patient outcomes were reported using the International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC-26) questionnaires at baseline and at each follow-up visit. ResultsMedian follow-up for the experimental arm was 48.5 months compared to 47 months and 60 months compared to the 36/12 and 37,5/15 groups respectively.The IPSS and EPIC scores did not demonstrate any significant differences in the gastrointestinal or genitourinary domains between the three groups over time. No biochemical recurrence occurred in the UHF arm as defined by the Phoenix criterion. ConclusionThe UHF treatment scheme with HDR BB seems equivalent to standard treatment arms in terms of toxicities and local control. Randomized control trials with larger cohorts are ongoing and needed to further confirm our findings.

Magnetic Resonance-Guided Adaptive Radiation Therapy for Prostate Cancer: The First Results from the MOMENTUM study—An International Registry for the Evidence-Based Introduction of Magnetic Resonance-Guided Adaptive Radiation Therapy

Magnetic resonance (MR)-guided radiation therapy (MRgRT) is a new technique for treatment of localized prostate cancer (PCa). We report the 12-month outcomes for the first PCa patients treated within an international consortium (the MOMENTUM study) on a 1.5T MR-Linac system with ultrahypofractionated radiation therapy. Patients treated with 5×7.25 Gy were identified. Prostate specific antigen-level, physician-reported toxicity (Common Terminology Criteria for Adverse Events [CTCAE]), and patient-reported outcomes (Quality of Life Questionnaire PR25 and Quality of Life Questionnaire C30 questionnaires) were recorded at baseline and at 3, 6, and 12 months of follow-up (FU). Pairwise comparative statistics were conducted to compare outcomes between baseline and FU. The study included 425 patients with localized PCa (11.4% low, 82.0% intermediate, and 6.6% high-risk), and 365, 313, and 186 patients reached 3-, 6-, and 12-months FU, respectively. Median prostate specific antigen level declined significantly to 1.2 ng/mL and 0.1 ng/mL at 12 months FU for the nonandrogen deprivation therapy (ADT) and ADT group, respectively. The peak of genitourinary and gastrointestinal CTCAE toxicity was reported at 3 months FU, with 18.7% and 1.7% grade ≥2, respectively. The QLQ-PR25 questionnaire outcomes showed significant deterioration in urinary domain score at all FU moments, from 8.3 (interquartile range [IQR], 4.1-16.6) at baseline to 12.4 (IQR, 8.3-24.8; P=.005) at 3 months, 12.4 (IQR, 8.3-20.8; P=.018;) at 6 months, and 12.4 (IQR, 8.3-20.8; P=.001) at 12 months. For the non-ADT group, physician- and patient-reported erectile function worsened significantly between baseline and 12 months FU. Ultrahypofractionated MR-guided radiation therapy for localized PCa using a 1.5T MR-Linac is effective and safe. The peak of CTCAE genitourinary and gastrointestinal toxicity was reported at 3 months FU. Furthermore, for patients without ADT, a significant increase in CTCAE erectile dysfunction was reported at 12 months FU. These data are useful for educating patients on expected outcomes and informing study design of future comparative-effectiveness studies.

144 (PB-057) Poster - Ultrahypofractionated radiation therapy for breast cancer: two-year normal tissue effects

Introduction: Parallel with the emerging results of the FAST-Forward (FF) trial, we implemented ultrahypofractionated radiation therapy (RT) for early-stage breast cancer in our clinic at the beginning of the COVID-19 pandemic [Brunt 2020]. This scheme of 26 Gy in 5 consecutive fractions, was given to all breast cancer patients referred for postoperative RT of the breast only. Uniquely, in view of the pandemic, we also gave a single ultrahypofractionated sequential tumourbed boost of 6 Gy, if indicated according to our local protocol.

Changes in Fractionation Schedules for Breast Cancer Treatment during the COVID-19 Pandemic

Purpose/Objective(s)In 2020, 5-year results of the FAST-Forward trial and 10-year results for both the FAST trial and APBI-IMRT-Florence trials using ultrahypofractionated radiation (UHFR) were all published, each detailing equivalent outcomes for partial and whole breast UHFR schedules compared to more conventional fractionation regimes in early-stage breast cancer. Due to concerns over viral exposure, these treatment regimens were adopted in an effort to minimize patient exposure while achieving equivalent oncologic control. The purpose of this study was to compare the use of UHFR schedules for breast cancer patients before COVID-19, at the height of the pandemic and after widespread vaccination and analyze factors predictive of use.Materials/MethodsBetween October 2019 and February 2022, 733 patients with stage 0 or I breast cancer were offered radiation at our institution following breast conserving surgery. 43 patients were excluded (35 declined radiation and 8 received partial breast re-irradiation). We analyzed target volume (whole vs partial breast) and fractionation schemes (1 week vs 3 or more weeks) for 3 time periods of interest: pre-COVID-19 (October 2019-March 2020), height of COVID-19 (March 2020-March 2021) and post-COVID-19 vaccine (March 2021-February 2022). Fisher's exact test was used to compare frequencies of treatment parameters across groups and time periods. Logistic regression was used to determine factors associated with UHFR use. R (v4.1.2) was used for analysis.ResultsThe use of UHFR increased during the post-vaccine period as compared to pre-Covid-19 and the pre-vaccine time periods (p<0.001), with 4.6%, 9.2% and 23%, receiving UHFR respectively. On univariate analysis in the pre-vaccine time period, patients with grade 2 and 3 cancers were less likely to get UHFR (p = 0.003 and p = 0.005, respectively). Receiving radiation from an academic attending was associated with higher use of UHFR (p = 0.0004). On multivariate (MVA) patients with grade 2 and 3 disease remained less likely to get UHFR (p 0.001 and 0.004). Treatment by an academic attending remained a significant factor for use of UHFR (p=0.0003). In the post-vaccine time period, on univariate analysis, negative ER status and grade 3 tumors were associated with less use of UHFR (p = 0.04 and p = 0.0001, respectively). On MVA, only grade 3 was associated with less UHFR use (p = 0.0002).ConclusionDuring COVID there was a significant increase in the use of UHFR regimens for treatment of early-stage breast cancer patients at our institution that persisted and increased after the introduction of the vaccine despite return to pre-COVID patient volumes. Uptake of these new regimens was initially higher among academic radiation oncologists, however with education of community physicians and implementation of treatment planning scorecards, widespread adoption was seen.

Favorable outcome in advanced pheochromocytoma and paraganglioma after hypofractionated intensity modulated radiotherapy.

The purpose of this study was to review outcomes of patients with advanced/metastatic pheochromocytoma/paraganglioma (PPGL) treated at our institution with Intensity-modulated radiotherapy (IMRT), describe the treatment outcomes, and determine predictors. A retrospective study on patients with advanced/metastatic PPGL who received IMRT at Peking Union Medical College Hospital between 2014 and 2019. A total of 14 patients with 17 lesions were included in this study. Ultra-hypofractionated radiation therapy was used for 7 lesions in 5 patients, while hypofractionated radiation therapy was used for 8 lesions in 7 patients. 2 patients got conventional fractionated radiotherapy. Patients who received external beam radiation therapy were given a median total radiation dose of 74.4/130Gy (BED10/3) in a median of 13 fractions. OS at 2years was 78% for all patients. For lesions evaluated by RECIST response, at least stable disease of the target lesion was achieved in 94% and distant progression in 28.5%, with an average time to progression of 5.2months. Patients with locally advanced primary tumors or recurred in situ (n = 8) achieved 100% local control, and none of them got recurrence or distant metastasis after radiotherapy at last follow-up (median 29months). Of patients with catecholamine-related syndromes (n = 12), 91% of symptomatic lesions improved following radiation therapy and a more than 50% decline in catecholamines. We have found hypofractionated IMRT effective as an additional therapy for patients with advanced primary tumors or recurrence in situ and not amenable to complete surgical resection.