Radiation Therapy Oncology Group Research Articles

Early Endpoints in High-risk Localized Prostate Cancer: Exploratory Analysis of Three Radiation Therapy Oncology Group Phase 3 Studies

BackgroundEarly endpoints in clinical trials of high-risk localized prostate cancer (HRLPC) that resemble those monitored in real-world practice could expedite clinical development. ObjectiveTo assess the association of prostate-specific antigen (PSA) recurrence (PSA-R)-based early endpoints with metastasis-free survival (MFS), overall survival (OS), and prostate cancer (PC)-specific survival (PCSS), and to identify clinically undetectable disease. Design, setting, and participantsA post hoc analysis of patients with HRLPC from Radiation Therapy Oncology Group studies 9202, 9902, and 0521 was performed. InterventionLong-term adjuvant androgen-deprivation therapy (ADT) and post-primary definitive radiotherapy. Outcome measurements and statistical analysisEvent-free survival (EFS; PSA-R, locoregional recurrence [LRR], distant metastasis [DM], or death), biochemical failure (PSA-R), general clinical failure (PSA-R, LRR, DM, ADT initiation, or death), and no evidence of disease (NED; alive patients without PSA-R, LRR, DM, and subsequent PC therapy, and with testosterone recovery) were assessed for association with MFS, OS, and PCSS using correlation and landmark analyses, Kaplan-Meier method, and Cox proportional-hazard model. PSA-R was defined as PSA nadir + 2 ng/ml; PSA nadir + 2 ng/ml and rising; PSA >5, 10, and 25 ng/ml; or PSA doubling time (PSADT) <6 mo. Results and limitationsAmong assessed early endpoints, EFS with PSA nadir + 2 ng/ml and rising, or with PSA >5 ng/ml was associated with MFS, OS, and PCSS. No development of EFS with PSADT <6 mo or ADT initiation event or achievement of NED at 3 yr was associated with prolonged OS, MFS, and PCSS (hazard ratio [95% confidence interval], 0.53 [0.45–0.64], 0.63 [0.52–0.76], and 0.26 [0.18–0.36], or 0.56 [0.48–0.66], 0.62 [0.52–0.74], and 0.26 [0.19–0.37]) after the landmark time. Older studies performed before the current guidance should be interpreted with caution. ConclusionsWe identified EFS with PSA nadir + 2 ng/ml and rising, PSA >5 ng/ml, or PSADT <6 mo ± ADT initiation and NED as potentially promising early endpoints in HRLPC that should be validated further. Patient summaryWe identified novel clinical measures that may expedite the development of new medicines for patients with localized prostate cancer at a high risk of progression. These measures, which took into account prostate-specific antigen assessments and other clinical characteristics, should be confirmed in future studies. We also defined a novel measure of no evidence of disease that can help treating physicians identify patients with clinically undetectable disease.

Canine salivary gland carcinoma treated with stereotactic body radiation therapy: a retrospective case series.

The aim of this study was to describe the therapeutic outcomes of dogs with locally advanced salivary gland carcinomas (SGC) following stereotactic body radiation therapy (SBRT). A single institution retrospective study was conducted of client-owned dogs with macroscopic SGC treated with SBRT. Patient signalment, clinical characteristics, and treatment parameters were recorded. Clinical benefit was determined based on follow-up physical examination and medical history. Progression-free interval (PFI), median survival time (MST), and disease-specific survival (DSS) were calculated using Kaplan-Meier analysis. Acute and late toxicity were recorded according to Veterinary Radiation Therapy Oncology Group (VRTOG) criteria. Six patients were included in the study. Tumor origins were mandibular (n = 3), parotid (n = 2), and zygomatic (n = 1) salivary glands. The SBRT prescription was 10 Gy × 3 daily or every other day. All patients (100%) experienced clinical benefit from treatment at a median time of 34 days (range 28-214). No local or regional nodal failure was reported following SBRT. Progressive pulmonary metastatic disease was documented in three dogs (50%). The median PFI was 260 days (range 43-1,014) and the MST was 397 days (range 185-1,014). Median DSS was 636 days (range 185-1,014). Four dogs (66.6%) died of confirmed or suspected metastatic SGC. The reported acute side effects included grade 2 mucositis (n = 1) and vision loss (n = 1). No late side effects were recorded. This study suggests that SBRT may provide durable local control for invasive SGC in dogs. Further investigation in a larger cohort of patients is warranted. The incidence of reported acute and late toxicity was low.

Interpretable Machine Learning for Choosing Radiation Dose-volume Constraints on Cardio-pulmonary Substructures Associated with Overall Survival in NRG Oncology RTOG 0617

Our objective was to use interpretable machine learning for choosing dose-volume constraints on cardiopulmonary substructures (CPSs) associated with overall survival (OS) in radiation therapy for locally advanced non-small cell lung cancer. A total of 428 patients with non-small cell lung cancer were randomly divided into training/validation/test subsets (n=230/149/49) in Radiation Therapy Oncology Group 0617. Manual or automated contouring was performed to segment CPSs, including heart, atria, ventricles, aorta, left/right ventricle/atrium (LV+RV+LA+RA), inferior/superior vena cava, pulmonary artery, and pericardium. Peri (pericardium-heart), rest (heart-[LV+RV+LA+RA]), clinical target volume (CTV), and lungs-CTV contours were also obtained. Dose-volume histogram features were extracted, including minimum/mean dose to the hottest x% volume (Dx%[Gy]/MOHx%[Gy]), minimum/mean/maximum dose, percent volume receiving at least xGy (VxGy[%]), and overlapping volume of each CPS with planning target volume (PTV_Voverlap[%]). Clinical parameters were collected from the National Clinical Trials Network/Community oncology research program data archive. Feature selection was performed using a series of multiblock sparse partial least squares regression, stability selection supervised principal component analysis, and Boruta. Explainable boosting machine (EBM) was trained using a conditional survival distribution-based approach for imputing censored data, treating survival analysis as a regression problem. Harrell's C-index was used to evaluate OS discrimination performance of EBM, Cox proportional hazards (CPH), random survival forest, extreme gradient boosting survival embeddings, and CPH deep neural network (DeepSurv) models in the test set. Dose-volume constraints were selected using the binary change point detection algorithm in Shapley additive explanations-based partial dependence functions. Selected features included LA_V60Gy(%), pericardium_D30%(Gy), lungs-CTV_PTV_Voverlap(%), RA_V55Gy(%), and received_cons_chemo. All models ranked LA_V60Gy(%) as the most important feature. EBM achieved the best performance for predicting OS, followed by extreme gradient boosting survival embeddings, random survival forest, DeepSurv, and CPH (C-index=0.653, 0.646, 0.642, 0.638, and 0.632). EBM global explanations suggested that LA_V60Gy(%) < 25.6, lungs-CTV_PTV_Voverlap(%) < 1.1, pericardium_D30%(Gy) < 18.9, RA_V55Gy(%) < 19.5, and received_cons_chemo='Yes' for improved OS. EBM can be used to discriminate OS while also guiding dose-volume constraint selection for optimal management of cardiac toxicity in lung cancer radiation therapy.

A phase II randomized clinical trial to assess toxicity and quality of life of breast cancer patients with hypofractionated versus conventional fractionation radiotherapy with regional nodal irradiation in the context of COVID-19 crisis.

This study, conducted during the COVID-19 crisis, primarily aimed to compare the acute toxicity between conventional fractionated radiation therapy (CF-RT) with hypofractionated radiation therapy (HF-RT) among patients who underwent breast-conserving surgery or mastectomy in whom breast or chest wall and regional nodal irradiation (RNI) were indicated. The secondary endpoints were both acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. In this open and non-inferiority randomized trial, patients (n = 86) were randomly allocated 2:1 in the CF-RT arm (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus the HF-RT arm (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE) and the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy Oncology Group (RTOG) scale. For the patient-reported quality of life (QoL), the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23) were used. Lymphedema was assessed by comparing volume differences between the affected and contralateral arms using the Casley-Smith formula. Grade 2 and grade 3 dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, and 0% vs. 6%, respectively; p = 0.022). HF-RT had a lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005), compared to CF-RT. No other differences in overall rates of physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT and CF-RT were registered. There was no statistical difference between groups regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000), and functional and symptom scales, during both the irradiation period and after 6 months of the end of treatment. The results revealed that the subset of patients up to 65 years or older did not show a statistical difference between both arm fractionation schedules (p > 0.05) regarding skin rash, fibrosis, and lymphedema. HF-RT was non-inferior to CF-RT, and moderate hypofractionation showed lower rates of acute toxicity, with no changes in quality-of-life outcomes. ClinicalTrials.gov, identifier NCT40155531.

Elective Nodal Irradiation for Oligorecurrent Nodal Prostate Cancer: Interobserver Variability in the PEACE V-STORM Randomized Phase 2 Trial

Consistency in delineation of pelvic lymph node regions for prostate cancer elective nodal radiation therapy is still challenging despite current guidelines. The aim of this study was to evaluate the interobserver variability in elective lymph node delineation in the PEACE V- STORM randomized phase 2 trial for oligorecurrent nodal prostate cancer. Twenty-three centers were asked to delineate the elective pelvic nodal clinical target volume (CTV) of a postoperative oligorecurrent nodal prostate cancer benchmark case using a modified Radiation Therapy Oncology Group (RTOG) 2009 template (upper limit at the L4/L5 interspace). Overall, intersection and overflow volumes, Dice coefficient, Hausdorff distance, and count maps merged with computed tomography images were analyzed. The mean volume including the 23 nodal CTVs was 430.4 ± 64.1 cm3, larger than the modified RTOG 2009 CTV reference volume (386.1 cm3). The intersection common volume between the modified reference RTOG 2009 and the 23 nodal CTVs was estimated at 83.9%, whereas the overflow volume was 23.4%, mainly located at the level of the presacral and the upper limit of the L4/L5 interspace. The mean Dice coefficient was 0.79 ± 0.02, whereas the mean Hausdorff distance was 27 ± 4.4 mm. In salvage radiation therapy treatment of oligorecurrent nodal prostate cancer, variations in elective lymph node volume delineation were mainly observed in the presacral and common iliac areas. Routine implementation and diffusion of available contouring guidelines together with a constant evaluation and evidence-based updating are expected to further decrease the existing variability in pelvic node contouring.

Topical corticosteroids for the prevention of severe radiation dermatitis: a systematic review and meta-analysis.

Radiation dermatitis (RD) is a frequently occurring adverse reaction during radiotherapy in cancer patients. While the use of topical corticosteroids (TCs) is common for the treatment of RD, its role in preventing severe reactions remains unclear. This systematic review and meta-analysis aim to evaluate the evidence on the use of TCs as prophylaxis of RD. A systematic search was conducted using OVID MedLine, Embase, and Cochrane databases (between 1946 and 2023) to identify studies examining TC use in the prevention of severe RD. Statistical analysis was completed using RevMan 5.4 to calculate pooled effect sizes and 95% confidence intervals. Forest plots were then developed using a random effects model. Ten RCTs with a total of 1041 patients met the inclusion criteria. Six studies reported on mometasone furoate (MF) and four studies reported on betamethasone. Both TCs were associated with a significant improvement in the prevention of moist desquamation [OR = 0.34, 95% CI [0.25, 0.47], p < 0.00001], but betamethasone was found to be more effective than MF [OR = 0.29, 95% CI [0.18, 0.46], p < 0.00001 and OR = 0.39, 95% CI [0.25, 0.61], p < 0.0001, respectively]. A similar finding was seen in reducing the development of grade 2 or higher RD according to the Radiation Therapy Oncology Group scale. The current evidence supports the use of TCs in preventing severe reactions of RD. Both MF and betamethasone were found to be effective; however, betamethasone, a higher potency TC, is more effective despite MF being more commonly reported in literature.

Optimizing surface mould brachytherapy for treatment of nasal basal cell carcinoma using customized applicators

PURPOSESurface mould brachytherapy (SMBT) is ideal in treating superficial skin cancer over the curved surface of the nasal ala. We describe the process of initiating and optimizing SMBT treatment at our institution including clinical workflow, generation of three dimensional (3D) printed custom applicators, and clinical outcomes. METHODS AND MATERIALSPlanning CT scans were used to acquire images for delineating target volumes. The applicator was designed with customized catheter positioning (3–5mm from target) to cover target volume while sparing dose to organs at risk (OAR) such as adjacent skin and nasal mucosa. Applicators were 3D printed, with transparent resin to aid visualization of underlying skin. Dosimetric parameters evaluated included CTV D90, CTV D0.1cc, and D2cc to OARs. Clinical outcomes assessed were local control, acute and late toxicity (Common Terminology Criteria for Adverse Events v5.0 [CTCAEv5.0]), and cosmesis (Radiation Therapy Oncology Group [RTOG]). RESULTSTen patients were treated with SMBT with a median followup of 17.8 months. Dose prescription was 40 Gy in 10 daily fractions. Mean CTV D90 was 38.5 Gy (range 34.7–40.6), mean CTV D0.1cc 49.2 Gy (range 45.6–53.5), which was <140% of the prescription dose in all patients. Treatment was well tolerated, with acceptable Grade 2 acute, Grade 0–1 late skin toxicity, and good-excellent cosmesis for all patients. Two patients experienced local failure, and both underwent surgical salvage. CONCLUSIONSSMBT was successfully planned and delivered for superficial nasal BCC using 3D printed custom applicators. Excellent target coverage was achieved while minimizing dose to OAR. Toxicity and cosmesis rates were good-excellent.

Long-term Outcomes of Bevacizumab and Chemoradiation for Locoregionally Advanced Nasopharyngeal Carcinoma

The long-term outcomes associated with adding bevacizumab, a vascular endothelial growth factor inhibitor, to standard chemoradiation have continued to be favorable for a group of patients with locoregionally advanced nasopharyngeal carcinoma (NPC). To assess long-term toxic effects and clinical outcomes associated with chemotherapy, radiation therapy (RT), and bevacizumab for NPC. This single-arm phase II nonrandomized controlled trial was conducted by the National Cancer Trials Network group and NRG Oncology (formerly Radiation Therapy Oncology Group), with accrual from December 13, 2006, to February 5, 2009, and data analysis from June 26 to July 1, 2019. The study was conducted at 19 cancer centers with a median (IQR) follow-up of 9.0 (7.7-9.3) years. Included patients were adults (aged ≥18 years) with NPC that was World Health Organization (WHO) histologic grade I to IIb or III, American Joint Committee on Cancer stage IIB or greater, and with or without lymph node involvement. Patients received 3 cycles of bevacizumab (15 mg/kg) concurrently with standard cisplatin (100 mg/m2) and RT (69.96 Gy) followed by 3 cycles of adjuvant bevacizumab (15 mg/kg) given concurrently with cisplatin (80 mg/m2) and fluorouracil (1000 mg/m2/d). The primary end point was grade 4 hemorrhage or grade 5 adverse events in the first year. Secondary end points were locoregional progression-free (LRPF) interval, distant metastasis-free (DMF) interval, progression-free survival (PFS), overall survival (OS), and other adverse events. Long-term toxic effects and clinical outcomes were reported due to the limited follow-up in the initial report for this trial and the importance of long-term outcomes when combining bevacizumab with chemoradiation. Among 46 patients with NPC who were enrolled, 44 patients were analyzed (29 males [65.9%]; 23 Asian [52.3%], 2 Black [4.5%], and 16 White [36.4%]; 38 not Hispanic [86.4%]; median [IQR] age, 48.5 [39.0-56.0] years). There were 33 patients with a Zubrod performance status of 0, indicating that they were fully functional and asymptomatic (75.0%); 32 patients with a WHO histologic grade of IIb or III (72.7%); and 39 patients with stage III or IVB disease (88.6%). Among analyzed patients, 42 individuals received radiation therapy of 69.96 Gy or greater (95.5%; dose range, 65.72-70.00 Gy); 30 patients received 3 cycles of cisplatin (68.2%) with RT, and 31 patients received 3 cycles of bevacizumab with RT (70.5%); this was followed by 3 cycles of adjuvant cisplatin in 21 patients (47.7%), fluorouracil in 24 patients (54.5%), and bevacizumab in 23 patients (52.3%). No grade 4 hemorrhage or grade 5 AEs were reported in the first year or thereafter. Late grade 3 AEs occurred in 16 patients (36.4%), including 7 patients with dysphagia (15.9%), 6 patients with hearing impairment (13.6%), and 2 patients with dry mouth (4.5%). The 1- and 5-year rates of feeding tube use were 5 of 41 patients (12.2%) and 0 of 27 patients, respectively. There were 19 patients (43.2%) who progressed or died without disease progression (6 patients with locoregional progression [13.6%], 8 patients with distant progression [18.2%], and 5 patients who died without progression [11.4%]). The 5- and 7-year rates were 79.5% (95% CI, 67.6%-91.5%) and 69.7% (95% CI, 55.9%-83.5%) for OS, 61.2% (95% CI, 46.8%-75.6%) and 56.3% (95% CI, 41.5%-71.1%) for PFS, 74.9% (95% CI, 61.4%-86.6%) and 72.3% (95% CI, 58.4%-84.7%) for LRPF interval, and 79.5% (95% CI,66.4%-90.0%) for both times for DMF interval. Among 13 patients who died, death was due to disease in 8 patients (61.5%). In this nonrandomized controlled trial, no grade 4 hemorrhage or grade 5 AEs were reported in the first year or thereafter among patients with NPC receiving bevacizumab combined with chemoradiation. The rate of distant metastasis was low although 89% of patients had stage III to IVB disease, suggesting that further investigation may be warranted. ClinicalTrials.gov Identifier: NCT00408694.

Career development: A balance of opportunities and choices.

Career development: A balance of opportunities and choices.

Ten-year outcomes of hypofractionated (45 Gy in 9 fractions) intensity-modulated radiotherapy for localized prostate cancer.

e17100 Background: We reported 10-year outcomes of localized prostate cancers treated with hypofractionated intensity-modulated radiotherapy of 45 Gy in 9 consecutive fractions. Methods: From October 2011 to April 2017, thirty patients with localized prostate cancer were enrolled in this prospective trial. The median age of the patients was 72.5 years. According to NCCN recurrence risk criteria, eight patients were at low risk group, 17 at intermediate risk group, 5 at high risk group. All patients were treated with hypofractionated intensity-modulated radiotherapy (IMRT) of 45 Gy in 9 consecutive fractions to their prostate with or without seminal vesicles. Before radiotherapy, three gold fiducials were implanted into the prostate. In order to reduce the rectal high dose irradiation volume , an inflated rectal balloon was placed in the rectum at simulation and every treatment and patients were treated with comfortable full bladder. Static Intensity-modulated radiotherapy (SIMRT) was applied in 1 patient, Volumetric Modulated Arc Therapy (VMAT) in 27 patients, and tomotherapy in 2 patients. Image guided radiotherapy (IGRT) with gold fiducial registration was adopted. Twenty-six patients also received androgen deprivation therapy (ADT). The median time of ADT was 6 months. Progression⁃free survival(PFS) and overall survival(OS) were analyzed using Kaplan-Meier analysis. All grade ≥1 genitourinary (GU) and gastrointestinal (GI) toxicities were recorded using Common Terminology Criteria for Adverse Event version 5.0 (CTCAE 5.0) and Radiation Therapy Oncology Group (RTOG) late morbidity criteria , and GU and GI toxicities were cumulatively calculated. Results: After a median follow-up of 102 months (65~131 months), the 10-year OS was 90.0%(95% confidence interval, 83.3%-96.7%), and the 10-year PFS was 86.5% (95% confidence interval, 79.1%-93.9%). According to CTCAE 5.0, grade 1 acute gastrointestinal (GI) toxicity developed in 12 patients, grade 2 in 2 patients, grade 3 in 2 patients, and grade 1 acute genitourinary (GU) toxicity developed in 12 patients, grade 2 in 2 patients, and no grade 3 or higher toxicity occurred. According to RTOG late morbidity criteria, late (≥3 months after radiotherapy) grade 1 GI toxicity developed in 4 patients (13.3%), grade 2 in 1 (3.3%), grade 3 in 1 (3.3%), and late grade 1 GU toxicity occurred in 1 patient (3.3%), grade 2 in 1 (3.3%), grade 3 in 1 (3.3%). No grade 4 or higher GI and GU toxicities developed. Only one grade 3 GI and one grade 2 GU toxicities were observed for the maximum toxicity at the last follow-up. The potency was not evaluated. Conclusions: The 10-year oncologic outcomes of this shortened hypofractionated IMRT regimen for mainly low/intermediate risk prostate cancer patients is favorable with acceptable acute and late toxicities.

The role of image-guided volume-adapted high-dose-rate endorectal brachytherapy boost in total neoadjuvant treatment of distal locally advanced rectal cancer.

3611 Background: Endorectal brachytherapy has been used as palliative or preoperative treatment for advanced or locally advanced rectal cancer, with moderate radiation induced toxicity. This study aimed to explore the efficacy of high-dose-rate 192Ir brachytherapy combined with external beam radiotherapy (EBRT) in total neoajuvant treatment (TNT) of distal rectal cancer. Methods: From January 2017 to December 2022, eligible rectal adenocarcinoma patients were assessed as clinical stage II -III, with primary tumor located in distal rectum (≤5 cm from anal verge). The local staging was determined using endorectal ultrasound and magnetic resonance imaging (MRI). In addition, cases included in this study underwent preoperative semiweekly endorectal brachytherapy of 8-12Gy/2-3F/1-1.5w, followed by EBRT of 45-50.4Gy/25-28F, fluorouracil-based concurrent and consolidation chemotherapy. The brachytherapy was image-guided volume-adapted, and delivered by multi-channel 192Ir source applicators with different diameters. Radiation proctitis was graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: A total of 40 cases were enrolled in this retrospective study, biopsy-proven and diagnosed as clinical stage II (n = 8), stage III (n = 32). The rates of T4 and positive circumferential resection margin (CRM) were 35% and 87.5% respectively. The median value of the interval from completion of radiotherapy to operation was 86 days (interquartile range: 75-98 days). After neoadjuvant treatment, 2 cases were undergoing the watch-and-wait strategy with sustained clinical complete response (cCR), 38 patients received operation and R0 resection rate was 97.4%. The pathological complete response (pCR) rate was 28.9%, and major pathological regression rate was 67.5%. The theoretical rate of anus preservation was 62.5%, including 6 of 21 cases underwent abdominoperineal resection but achieved pCR, 17 cases underwent low anterior resection or intersphincteric resection, and 2 cases with sustained cCR. After a median follow-up of 37 months (range 12-68 months), the 3-year disease-free survival, local-regional reccurence-free survival and overall survival was 81.1% (95%CI: 64.3%-91.2%), 94.9% (95%CI: 80.6%-98.5%) and 96.9% (95%CI: 82.1%-99.4%), respectively. No patients experienced Grade ≥3 radiation proctitis. The median Wexner fecal incontinence score of anus-preserving cases was 1 (range 0-8). Subgroup analysis showed that the complete response rate (pCR or sustained cCR) was lower in cases received 2 fractions brachytherapy than those received 3 fractions (27.8% vs 36.4%). Conclusions: The addition of image-guided volume-adapted high-dose-rate 192Ir endorectal brachytherapy boost to TNT could improve the pathological tumor response and anus preservation rate in distal locally advanced rectal cancer.

High-Grade Pneumonitis Events in Patients With Unresectable, Locally Advanced NSCLC Treated With Definitive Chemoradiation Followed By Adjuvant Durvalumab

BackgroundThe standard of care for unresectable locally advanced NSCLC is concurrent chemotherapy and radiation (CRT) followed by adjuvant durvalumab, established by the PACIFIC trial, which revealed acceptable although higher rates of pneumonitis with durvaluamb than placebo. We retrospectively reviewed patients with locally advanced NSCLC from 2018 to 2022 treated with definitive CRT (≥60 Gy) followed by at least one dose of adjuvant durvalumab. ObjectiveTo review the incidence of pneumonitis and contributing factors, and also to review grade 5 pneumonitis (G5) events. MethodsWe identified 78 cases with a median age of 70.0 years and a median follow-up of 36 months. All patients received CRT of at least 60 Gy at 2 Gy per fraction. A total of 22 patients (28.2%) completed 12 months of durvalumab. The cumulative incidence of any-grade pneumonitis was 28.2%. Pneumonitis rate in grades 1, 2, 3, 4, and 5 was 1.3%, 10.3%, 7.7%, 0.0%, and 9.0%, respectively. ResultsMultivariate analysis did not reveal significant factors associated with G5 pneumonitis. There were 8 patients who received radiation therapy doses above standard limits and, of these, only two developed G5 pneumonitis. All patients with G5 pneumonitis had multiple comorbidities and/or previous malignancy treated with systemic therapy. The median overall survival was 31.1 months and the median progression-free survival was 12.7 months. ConclusionsWe report comparable overall rates of pneumonitis relative to published data with higher rates of G5 pneumonitis. Patients with high-dose radiation therapy (≥60 Gy) and Eastern Cooperative Oncology Group performance status greater than or equal to 2 may tolerate adjuvant durvalumab, though providers should exercise caution in patients with extensive comorbidities.

Efficacy and toxicity of hypofractionated radiation therapy for patients with hematologic malignancies: update on a COVID era ILROG collaborative report

Purpose/Objectives: During COVID19, shorter radiation therapy (RT) courses were considered to minimize patient exposure, ensure staff safety, and conserve healthcare resources. Due to concerns with the safety of systemic therapy, RT demands were also increased. In response, guidelines were published by the International Lymphoma Radiation Oncology Group (ILROG) to guide the treatment of hematologic malignancies patients with hypofractionated radiation therapy (hRT) regimens. These guidelines suggested hRT dose/fractionation schemes based on the known radiosensitivity of various hematologic malignancies with consideration of the biologically equivalent doses in the hRT setting. However, the outcomes for these dose/fractionation regimens in terms of efficacy and toxicity are unknown. Materials/Methods: In collaboration with ILROG, we performed a retrospective multinational, multicenter study. We included any patient treated from 1/1/2020 to 8/31/2020 with hRT given according to the published ILROG guidelines or hRT given at >3 Gy per fraction. We abstracted patient and treatment data from the respective institutional databases. CTCAE v5.0 was used to grade toxicity. Results: We included 237 patients from 8 different institutions treated with 282 RT courses. Patient and treatment details are reported in Table 1. Median RT dose was 12 Gy (range 4–39) in a median of 3 fractions (range 1–13). Median follow up was 181 days, with 174 patients (73%) alive at last follow up. Response within the RT field was assessed in 228 sites: complete response (CR) (n = 143, 63%); partial response (PR) (n = 59, 26%); stable disease (SD) (n = 15, 7%); and progressive disease (PD) (n = 11, 5%). Maximal toxicities reported were Grade 1 (n = 45), Grade 2 (n = 24), Grade 3 (n = 4) and Grade 4 (n = 1). Grade 3 toxicities occurred with the following treatment regimens: 12 Gy in 3 fx to extremity (dermatitis, given concurrent with methotrexate); 30 Gy in 6 fx to extremity (dermatitis); 20 Gy in 5 fx to pelvis (pain); 25 Gy in 5 fx to abdomen (pain). One grade 4 toxicity occurred with 12 Gy in 3 fx to the CNS (hematologic toxicity). Conclusions: Treatment of hematologic malignancies patients with hRT was generally well tolerated with few unexpected toxicities. Evaluation of efficacy is limited by patient and treatment heterogeneity but appears to be reasonable. These data can provide guidance for emergency situations requiring minimization of patient and staff exposure. Perhaps more importantly, hRT could be considered even in routine settings to spare patients time on treatment, especially for certain patient subgroups. Keyword: Radiation Therapy Conflicts of interests pertinent to the abstract. U. Ricardi Consultant or advisory role: Advisory Board member and Speaker Honoraria: Astra Zeneca Research funding: Institutional Research Cooperation: Accuray, BrainLab L. Specht Consultant or advisory role: Takeda, Kyowa Kirin, MSD Honoraria: Takeda Research funding: Varian, ViewRay, Danish Cancer Society

VERY LOW DOSE RADIATION THERAPY FOR INDOLENT LYMPHOMA: COMPARING “BIG BOOM” (4GY × 1) VERSUS “BOOM BOOM” (2GY × 2)

Purpose/Objectives: Indolent lymphomas are exquisitely sensitive to radiation therapy (RT). Programs of 2Gy × 2 were shown to be highly effective in controlling irradiated site(s). During the COVID-19 pandemic, the International Lymphoma Radiation Oncology Group (ILROG) proposed guidelines that offered substitution of the Boom Boom (2Gy × 2) regimen with Big Boom of 4Gy × 1. This report compares our center’s experience with both regimens. Materials/Methods: We included patients with indolent lymphomas in this retrospective single institution study. After April 2020, both options of very low dose and choice of a standard full dose of 24Gy were discussed with the patients. Patients were treated with a definitive or palliative intent depending on disease stage and prior therapy exposure. Patients treated with 24Gy are not included in this report. Overall response rate (ORR) was assessed with Lugano PET criteria at the initial post-RT imaging. Differences between the two groups were examined using the Fisher’s exact test and Mann-Whitney test. Results: We evaluated a total of 471 lesions in 386 patients, including 172 lesions (37%) treated with 4Gy × 1 and 299 lesions (63%) treated with 2Gy × 2. Table 1 summarizes the patient and treatment characteristics. Age at the time of RT and sex were not significantly different between the two groups. The 2Gy × 2 cohort was more likely to have follicular lymphomas (FL) (66% vs. 54%, p = 0.011), though the proportion of higher-grade FL was similar between cohorts. The ORR was similar (4Gy × 1 = 86%, 2Gy × 2 = 87%) at the first post-RT evaluation (median of 2 months from RT for both cohorts). There was no significant difference in the rate of complete response, partial response, stable disease, or progressive disease between the cohorts at initial post-RT imaging. For both regimens, no directly related short-term side effects were observed. Conclusions: Both the 4Gy × 1 and 2Gy × 2 regimens demonstrated excellent ORR at the initial post-RT imaging assessment among patients with indolent lymphomas. While longer term follow-up is required to confirm durability of these findings, our initial experience suggests that 4Gyx1 regimen recommended by ILROG during the pandemic is an effective treatment approach. FL Grade 3A FL Grade 3B FL Grade 1-2 7 (4.1%) 0 86 (50%) 7 (2.3%) 2 (0.7%) 188 (63%) >5 cm ≤5 cm Unknown 15 (8.7%) 96 (56%) 61 (35%) 40 (13%) 259 (87%) 0 Complete Response Partial Response Progressive Disease Stable Disease Not assessed yet 93 (62%) 35 (23%) 6 (4%) 15 (10%) 23 190 (64%) 68 (23%) 16 (5.4%) 24 (8.1%) 1 Keywords: indolent non-Hodgkin lymphoma, radiation therapy No conflicts of interests pertinent to the abstract.

The quality of life in nasopharyngeal carcinoma radiotherapy: A longitudinal study

ObjectiveThis article aims to longitudinally compare nasopharyngeal carcinoma (NPC) patients' quality of life (QoL) during radiotherapy (RT) and identify QoL correlates. MethodsThis study included 98 patients, with 85 completing full follow-up. Data were collected at baseline (T1), midpoint of RT (T2), and RT completion (T3), between October 2021 and November 2022. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). RIOM severity was evaluated by the toxicity criteria of Radiation Therapy Oncology Group (RTOG). The nutritional status was evaluated using the Nutritional Risk Screening 2002 (NRS 2002), body mass index (BMI), and the Patient-Generated Subjective Global Assessment (PG-SGA). The generalized estimating equation described the QoL evolution and correlated it with RIOM, nutritional status, and other influential factors. ResultsSignificant deterioration was observed in various subscales of EORTC QLQ-C30 during RT, including global health status (GHS), physical function, role function, emotional function, fatigue, nausea/vomiting, pain, insomnia, appetite loss, and constipation (all P ​< ​0.05). Substantial deterioration was also observed in RIOM, nutritional status, and part of hematological indexes (all P ​< ​0.05). The decline of QoL was associated with gender, age, education level, chemotherapy regimen, Karnofsky performance status (KPS) score, RIOM severity, NRS 2002 score, PG-SGA score, and lymphocyte level (all P ​< ​0.05). ConclusionsQoL declined during RT and were associated with certain factors. Healthcare professionals should focus on alleviating treatment-related complications and identifying individuals at high risk of malnutrition early to improve outcomes for patients with NPC.

The effect of breath-hold technique on conformal and intensity modulated radiotherapy techniques at right breast cancer radiotherapy including internal mammarian field

Background/Aim: Significantly lower heart doses can be achieved by breath-hold technique at left-sided breast cancer radiotherapy (RT). We see high doses at organs at risk such as lung, heart, and contralateral breast during right-sided breast cancer RT planning especially in the presence of RT indication for mammaria interna (MI) lymph nodes. This study compared RT-planning methods that are conformal with intensity-modulated RT (IMRT) with breath holding and free breathing for right-sided breast cancer RT including full axillary and MI lymph node fields. Methods: Computed tomography (CT) simulations were performed using free-breath (FB) and breath-hold (BH) methods in 10 patients with right-sided breast cancer. A total of 40 RT treatment plans were calculated. Right-sided breast, level 1-2-3 axillary regions, and MI regions served for the target-planning volume. Left-sided breast, heart, as well as right-sided and left lungs were contoured as critical organs according to the atlas of the "Radiation Therapy Oncology Group." We used a Varian Eclipse v.13 for treatment planning. Conformal “FieldinField” RT (FinFRT) and dynamic IMRT (dIMRT) planning were performed separately for each patient over breath-hold and free-breath images. For PTV, 50 Gy was prescribed in 25 fractions and optimized such that the planned target volume (PTV) remained between 95% and 110% of the dose. The mean and maximum doses of the heart, V5 and V20 of the lungs, as well as V95 doses for MI were recorded. Statistical analyses were performed with SPSS version 22, and a paired t-test was used for comparison. Results: Four treatment plans (FB FinFRT, BH FinFRT, FB dIMRT, BH dIMRT) were made separately for 10 patients. For comparison, common FB FinFRT plans were accepted as the baseline plan. As expected, there were no significant differences in PTV coverage. The mean dose received by 95% of the MI volume was between 42.27 Gy and 42.4 Gy. For the maximum heart dose, the breath hold technique had no significant effect on plans. The lowest average maximum heart dose was seen in the BH FinFRT group. Mean heart doses are between 1.28 Gy – 4.85 Gy. There was no significance between BH FinFRT and FB FinFRT plan (P=0.504), and there was a significant difference for heart mean dose versus dIMRT plans (P=0.001). The mean V20 of the lungs ranged from 11.9 to 17.8. There was a significant decrease in V20 with BH or FB dIMRT plans (P=0.001). There was no difference between BH FinFRT (P=0.138). On the contrary, lung V5 values were significantly higher in dIMRT plans, and the lowest mean V5 value was seen in BH FinFRT plan. Conclusion: With the BH method, lower doses (but not significantly lower doses) were obtained in critical organ doses. There was a significant decrease with FinFRT plans in terms of heart mean and maximum dose and lung V5 percentages. The dIMRT plans were significant only in lung V20 percentages. When planning RT, we recommend evaluating all treatment techniques individually for right-sided breast cancer patients to obtain lower doses in critical organs.

Single-Institution Prospective Evaluation of Moderately Hypofractionated Whole-Breast Radiation Therapy With Simultaneous Integrated Boost With or Without Lymphatic Drainage Irradiation After Breast-Conserving Surgery

We report treatment outcomes for patients who received adjuvant moderate hypofractionated whole-breast radiation therapy with simultaneous integrated boost (SIB-mhWBRT) after breast-conserving surgery. SIB-mhWBRT for patients with breast cancer was introduced in our department in July 2017. This prospective evaluation includes 424 consecutive patients treated with SIB-mhWBRT for stage I-III invasive breast cancer (n=391) and/or ductal carcinoma in situ (n=33) until December 2021. SIB-mhWBRT was applied with 40 Gy in 15 daily fractions over 3 weeks according to the START B trial, with an SIB dose to the tumor bed of 48 Gy according to Radiation Therapy Oncology Group 1005/UK-IMPORT-HIGH, delivered as 3-dinemsional conformal radiation therapy (RT; n=402), intensity modulated RT (n=4), or volumetric modulated arc therapy (n=18). The mean patient age was 60 years (range, 27-88). Since May 2018, patients with indications for lymphatic pathway RT were included (n=62). Baseline parameters and follow-up data were recorded and reported, including objective assessment of treatment-related outcomes and subjective patient-reported outcome measures (PROMs). Mean/median follow-up was 29/33 months (range, 2-60). Acute toxicity grade 0, 1, 2, and 3 was observed in 25.0%, 61.4%, 13.3%, and 0%, respectively, at the completion of RT. Data of 281, 266, 243, 172, and 58 patients were available for 6-month and 1-, 2-, 3-, and 4-year follow-up, respectively. Grade 2 late effects were identified in 8.5%, 6.0%, 4.9%, 2.2%, and 10.2% and grade 3 in 2.8%, 1.1%, 1.2%, 0%, and 0% of patients at 6-month and 1-, 2-, 3-, and 4-year follow-up, respectively. Medical treatment of breast edema was the only grade 3 late effect observed. PROM cosmesis results were evaluated as excellent-good, fair, and poor in 97.2%, 2.5%, and 0.4%; 96.5%, 3.1%, and 0.4%; 97.4%, 2.2%, and 0.4%; 97.5%, 2.5%, and 0%; and 96.5%, 3.5%, and 0.0% at 6 months and 1, 2, 3, and 4 years post-RT, respectively. For all patients, the 3-year overall, cancer-specific, and disease-free survival rates were 98.2%, 99.1%, and 95.9%, respectively. Three-year risk of any locoregional recurrence was 0.6%. No mortality or relapse was observed in patients with ductal carcinoma in situ. SIB-mhWBRT demonstrated very favorable side effect profiles and cosmesis/PROMs. Three-year results demonstrate excellent locoregional control. This short-term regimen offers substantial patient comfort and improves institutional efficacy.

Investigating Predictive Factors of Dysphagia and Treatment Prolongation in Patients with Oral Cavity or Oropharyngeal Cancer Receiving Radiation Therapy Concurrently with Chemotherapy

Radiation therapy (RT) treatment for head and neck cancer has been associated with dysphagia manifestation leading to worse outcomes and decrease in life quality. In this study, we investigated factors leading to dysphagia and treatment prolongation in patients with primaries arising from oral cavity or oropharynx that were submitted to radiation therapy concurrently with chemotherapy. The records of patients with oral cavity or oropharyngeal cancer that received RT treatment to the primary and bilateral neck lymph nodes concurrently with chemotherapy were retrospectively reviewed. Logistic regression models were used to analyze the potential correlation between explanatory variables and the primary (dysphagia ≥ 2) and secondary (prolongation of total treatment duration ≥ 7 days) outcomes of interest. The Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) were used to evaluate dysphagia. A total of 160 patients were included in the study. Age mean was 63.31 (SD = 8.24). Dysphagia grade ≥ 2 was observed in 76 (47.5%) patients, while 32 (20%) experienced treatment prolongation ≥ 7 days. The logistic regression analysis showed that the volume in the primary site of disease that received dose ≥ 60 Gy (≥118.75 cc, p < 0.001, (OR = 8.43, 95% CI [3.51-20.26]) and mean dose to the pharyngeal constrictor muscles > 40.6 Gy (p < 0.001, OR = 11.58, 95% CI [4.84-27.71]) were significantly associated with dysphagia grade ≥ 2. Treatment prolongation ≥ 7 days was predicted by higher age (p = 0.007, OR = 1.079, 95% CI [1.021-1.140]) and development of grade ≥ 2 dysphagia (p = 0.005, OR = 4.02, 95% CI [1.53-10.53]). In patients with oral cavity or oropharyngeal cancer that receive bilateral neck irradiation concurrently with chemotherapy, constrictors mean dose and the volume in the primary site receiving ≥ 60 Gy should be kept below 40.6 Gy and 118.75 cc, respectively, whenever possible. Elderly patients or those that are considered at high risk for dysphagia manifestation are more likely to experience treatment prolongation ≥ 7 days and they should be closely monitored during treatment course for nutritional support and pain management.

Long-Term Outcomes of TROG 13.01 SAFRON II Randomized Trial of Single- Versus Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In a randomized phase II clinical trial, the Trans Tasman Radiation Oncology Group compared single- versus multifraction stereotactic ablative body radiotherapy (SABR) in 90 patients with 133 oligometastases to the lung. The study found no differences in safety, efficacy, systemic immunogenicity, or survival between arms, with single-fraction SABR picked as the winner on the basis of cost-effectiveness. In this article, we report the final updated survival outcome analysis. The protocol mandated no concurrent or post-therapy systemic therapy until progression. Modified disease-free survival (mDFS) was defined as any progression not addressable by local therapy, or death. At a median follow-up of 5.4 years, the 3- and 5-year estimates for overall survival (OS) were 70% (95% CI, 59 to 78) and 51% (95% CI, 39 to 61). There were no significant differences between the multi- and single-fraction arms for OS (hazard ratio [HR], 1.1 [95% CI, 0.6 to 2.0]; P = .81). The 3- and 5-year estimates for disease-free survival were 24% (95% CI, 16 to 33) and 20% (95% CI, 13 to 29), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.6]; P = .92). The 3- and 5-year estimates for mDFS were 39% (95% CI, 29 to 49) and 34% (95% CI, 24 to 44), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.8]; P = .90). In this patient population, where patients receive SABR in lieu of systemic therapy, one-in-three patients are alive without disease in the long term. There were no differences in outcomes by fractionation schedule.

Salvage Radiation Therapy After Radical Prostatectomy: Analysis of Toxicity by Dose-Fractionation in the RADICALS-RT Trial

Emerging data indicate comparable disease control and toxicity of normal postoperative fractionation and moderate hypofractionation radiation therapy (RT) in prostate cancer. In RADICALS-RT, patients were planned for treatment with either 66 Gy in 33 fractions (f) over 6.5 weeks or 52.5 Gy in 20 f over 4 weeks. This non-randomized, exploratory analysis explored the toxicity of these 2 schedules in patients who had adjuvant RT. Information on RT dose was collected in all patients. The Radiation Therapy Oncology Group toxicity score was recorded every 4 months for 2 years, every 6 months until 5 years, then annually until 15 years. Patient-reported data were collected at baseline and at 1, 5, and 10 years using standard measures, including the Vaizey fecal incontinence score (bowel) and the International Continence Society Male Short-Form questionnaire (urinary incontinence). The highest event grade was recorded within the first 2 years and beyond 2 years and compared between treatment groups using the χ² test. Of 634 patients, 217 (34%) were planned for 52.5 Gy/20f and 417 (66%) for 66 Gy/33f. In the first 2 years, grade 1 to 2 cystitis was reported more frequently among the 66 Gy/33f group (52.5 Gy/20f: 20% vs 66 Gy/33f: 30%; P=.04). After 2 years, grade 1 to 2 cystitis was reported in 16% in the 66-Gy group and 9% in the 52.5-Gy group (P=.08). Other toxic effects were similar in the 2 groups, and very few patients had any grade 3 to 4 toxic effects. Patients reported slightly higher urinary and fecal incontinence scores at 1 year than at baseline, but no clinically meaningful differences were reported between the 52.5 Gy/20f and 66 Gy/33f groups. Patient-reported health was similar at baseline and at 1 year and similar between the 52.5 Gy/20f and 66 Gy/33f groups. Severe toxic effects were rare after prostate bed radiation therapy with either 52.5 Gy/20f or 66 Gy/33f. Only modest differences were recorded in toxic effects or in patient-reported outcomes between these 2 schedules.