RT Dose Research Articles

Efficacy and Safety of 4 Fractions of Carbon-Ion Radiation Therapy for Hepatocellular Carcinoma: A Prospective Study

Introduction: Prospective evidence supporting the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for hepatocellular carcinoma (HCC) remains lacking. This prospective study aimed to evaluate the safety and efficacy of hypofractionated C-ion RT in patients with HCC. Methods: The inclusion criteria were as follows: (1) pathologically or clinically diagnosed HCC; (2) measurable tumor and tumor size ≤10 cm; (3) absence of major vascular invasion; (4) no extrahepatic metastasis; (5) the alimentary tract was not adjacent to the target lesion (>1 cm); (6) not suitable for or refusal to undergo surgery or local ablative therapies; (7) an interval ≥4 weeks from previous therapy; (8) no other intrahepatic lesion or at least 2 years after the previous curative therapy; (9) performance status score, 0–2; and (10) Child-Pugh score, 5–9. The prescribed C-ion RT dose was 52.8 Gy (relative biological effectiveness [RBE]) or 60.0 Gy (RBE) in 4 fractions. Results: In total, 35 patients with HCC were enrolled between October 2010 and May 2016. The median follow-up durations in the survivor group (n = 23) and in the whole cohort were 55.1 and 49.0 months, respectively. The 2-, 3-, and 4-year overall survival rates were 82.8%, 76.7%, and 69.4%, respectively. The 2-, 3-, and 4-year local control (LC) rates were 92.6%, 76.5%, and 76.5%, respectively. The median time-to-progression was 25.6 months (95% confidence interval, 13.7–37.5 months). Grade 4 or 5 toxicities were not observed. Grade 3 acute and late toxicities were observed in 2 patients. There was no significant deterioration in serum albumin, bilirubin, prothrombin time-international normalized ratio, platelet count, or Child-Pugh score after C-ion RT. Conclusion: Four fractions of C-ion RT for HCC did not yield serious adverse events and showed promising LC, thus making it a safe and effective modality for this type of malignancy.

Potential Benefits of a Minimal Dose Eccentric Resistance Training Paradigm to Combat Sarcopenia and Age-Related Muscle and Physical Function Deficits in Older Adults.

The ability of older adults to perform activities of daily living is often limited by the ability to generate high mechanical outputs. Therefore, assessing and developing maximal neuromuscular capacity is essential for determining age-related risk for functional decline as well as the effectiveness of therapeutic interventions. Interventions designed to enhance neuromuscular capacities underpinning maximal mechanical outputs could positively impact functional performance in daily life. Unfortunately, < 10% of older adults meet the current resistance training guidelines. It has recently been proposed that a more “minimal dose” RT model may help engage a greater proportion of older adults, so that they may realize the benefits of RT. Eccentric exercise offers some promising qualities for such an approach due to its efficiency in overloading contractions that can induce substantial neuromuscular adaptations. When used in a minimal dose RT paradigm, eccentric-based RT may be a particularly promising approach for older adults that can efficiently improve muscle mass, strength, and functional performance. One approach that may lead to improved neuromuscular function capacities and overall health is through heightened exercise tolerance which would favor greater exercise participation in older adult populations. Therefore, our perspective article will discuss the implications of using a minimal dose, submaximal (i.e., low intensity) multi-joint eccentric resistance training paradigm as a potentially effective, and yet currently underutilized, means to efficiently improve neuromuscular capacities and function for older adults.

NIMG-74. RESPONSE ASSESSMENT AFTER DOSE-ESCALATED RADIOTHERAPY: IMAGING PROTOCOL OF A MULTICENTER PHASE III TRIAL ON INTRAOPERATIVE RADIOTHERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA (INTRAGO-II;ARO2016-1;AG-NRO-03)

Abstract BACKGROUND Reliable response assessment of irradiated glioblastomas remains challenging. In an attempt to better distinguish post-therapeutic alterations (such as reactive gliosis, pseudoprogression and radionecrosis) from tumor progression, especially after (local) RT dose escalation as performed in the multinational INTRAGO-II trial, we modified the classical RANO criteria and developed a protocol and workflow for uniform assessment of post-irradiation tumor response. METHODS INTRAGO-II is a multinational randomized phase III trial (9 nations, 19 centers) that evaluates the benefit of intraoperative radiotherapy (IORT) with 20-30 Gy to the tumor bed after resection of glioblastoma in addition to standard of care (NCT02685605). Within this trial, advanced imaging is mandatory in addition to standard sequences and measurements (such as the sum of the products of perpendicular diameters, SPD). Specifically, the acquisition of dynamic susceptibility contrast (DSC) sequences as well as the calculation of the normalized relative cerebral blood volume (rCBV) is required. All local assessments are subjected to a central neuroradiology read, which is conclusive. The key modifications to RANO are that (i) an ≥25% increase SPD of the target lesions should be associated with a rCBV≥1 of at least one lesion to be considered radiological progression, (ii) new enhancing lesions should become measurable before they can constitute to radiological progression, (iii) rCBV is normalized against normal appearing white matter from the contralateral brain by reference ROI (with a minimal sphere size of 5x5mm) and (iv) confirmatory scans are mandatory for defining progressive disease. CONCLUSION/SUMMARY We present an imaging protocol based on updated RANO that accounts for post-irradiation image alterations. Funding: Carl Zeiss Meditec AG, Germany and MedWave Medical Imaging BV; Registered with ClinicalTrials.gov, number NCT02685605.

Comparison of the Pathological Response and Adverse Effects of Oxaliplatin and Capecitabine versus Paclitaxel and Carboplatin in the Neoadjuvant Chemoradiotherapy Treatment Approach for Esophageal and Gastroesophageal Junction Cancer: A Randomized Control Trial Study.

Background: Neoadjuvant chemoradiation is one of the main treatment approaches in esophageal cancer treatment, which can improve outcomes of a patient with esophageal cancer. In the current study, we aimed to compare the response rate and side effects of 2 distinctive neoadjuvant chemoradiation protocols. Methods: The study was a randomized clinical trial that was performed on 70 patients with esophageal and gastroesophageal junction cancer in Iran. The study participants were randomly assigned to 1 of our treatment groups. The first group received capecitabine (625 mg/m2/TID) and oxaliplatin (50 mg/m2/weekly), while the second group was given a combination of carboplatin (AUC:2/weekly) and paclitaxel (75mg/m2/weekly). Both groups were given weekly 50.4-54 Gy dose of RT. Chi square and Fisher exact tests have been used for data analysis. All statistical tests were performed using SPSS software Version 22.0 and the significance level was set at 0.05. Results: Complete pathological response was detected in 18(51.4%) of patients in group I and 8 (22.8%) in group II (p=0.013). We also observed higher thrombocytopenia in CarTax arm 19 (54.2%) in comparison to CapOX arm 8(22.8%), and the difference was statistically significant (p=0.007). No statistical difference was found regarding neutropenia, fatigue, anorexia, esophagitis, and diarrhea. Conclusion: The CapOxRT regime provides more favorable outcomes and also it is more tolerated by patients.

Outcomes and Patterns of Recurrence for Anaplastic Thyroid Cancer Treated With Comprehensive Chemoradiotherapy

PurposeRadiation therapy (RT) plays an important role in locoregional tumor control for anaplastic thyroid cancer (ATC). Due to its rarity, RT guidelines for ATC are lacking. We describe ATC patterns of nodal disease at presentation and progression and propose corresponding RT target volumes. Methods and MaterialsWe identified all patients with ATC treated at our institution with definitive or adjuvant intensity modulated radiation therapy and concomitant chemotherapy from 2006 to 2020. We identified in-field, marginal, and out-of-field sites of locoregional recurrence and progression (LRR). ResultsForty-seven patients met inclusion. Median follow-up was 6.6 months (interquartile range, 1.9-19.6). Nodal levels involved at presentation included: IB (2.1%), II (23.4%), III (21.3%), IV (21.3%), V (12.8%), VI (34%), and mediastinal (6.4%). All patients received elective nodal RT to levels II-IV and VI. RT volumes also included: IA (23.4%), IB (44.7%), V (87.2%), retropharyngeal/retrostyloid (RP/RS) (27.7%), and mediastinal 1 to 6 (53.2%). Cumulative incidence of LRR at 3- and 12-months was 26.1% (95% confidence interval, 15.9-42.8) and 35.7% (23.9-53.4). Isolated LRR risk at 3- and 12-months was 6.5% (2.2-19.8) and 8.9% (3.4-22.9). Fourteen (29.8%) patients experienced in-field LRR in the thyroid gland or postoperative tumor bed, II-IV, VI, and mediastinal 1 and 3A. Four (8.5%) patients had marginal LRRs, 3 of whom progressed in the mediastinum at 2, 3P, 4, and 6. Two (4.3%) patients experienced out-of-field LRRs. Throughout the pretreatment and follow-up period, no patients had disease at IA, and 1 (2.1%) patient each had disease at IB and RP/RS. No baseline or treatment characteristics, including RT dose (stratified by < or ≥66 Gy), were significant predictors of LRR on univariate analysis. ConclusionsIsolated LRR risk in patients with ATC treated with comprehensive RT and chemotherapy is low. Aggressive multimodality therapy should be reserved for willing, fit patients with no or limited distant disease burden. When treating comprehensively, complete inclusion of mediastinal levels 1 to 6 may be warranted to avoid marginal disease progression. Omission of levels I and RP/RS can be considered.

Risk of Recurrence and Patterns of Failure in Estrogen Receptor-Negative Ductal Carcinoma In Situ Patients

Ductal carcinoma in situ (DCIS) constitutes 15%-25% of newly diagnosed breast cancers. Similar to invasive breast cancer, DCIS tumors vary in terms of immunohistochemistry markers and pathological variables. For invasive carcinoma, treatment options and prognosis depend on these factors, including the expression of estrogen receptors (ER). ER negative (ER-) invasive breast cancers are known to be more aggressive. Treatment guidelines and prognosis for DCIS, however, are less well defined. Compared to ER+ DCIS, ER- DCIS is a far less common diagnosis, with 75% of DCIS expressing ER receptors. Data specific for ER- DCIS patients are thus lacking. The objective of this study was to investigate recurrence rates and patterns of failure of ER- DCIS in a single institution, and compare these statistics to the historic predominantly ER+ data in attempt to enhance risk stratification methods for DCIS patients in the future.We performed a retrospective review of medical records of DCIS patients diagnosed between 2004 and 2018, identifying 138 patients with ER negative tumors. 22 patients were lost to follow up immediately after diagnosis and were excluded from further analysis. Median follow up time for the remaining 116 patients was 46.5 months. Data on recurrence were collected. Statistical analysis included descriptive statistics, chi-square test, T-test for independent samples, and logistic regression.11 (9.5%) patients were found to have breast cancer recurrence. Median time to recurrence was 37 months. 8 (72.7%) patients developed a non-invasive recurrence (DCIS), with the remaining patients diagnosed with invasive ductal carcinoma (IDC). The recurrence was ipsilateral in 7 (63.6%) patients, and contralateral in the remaining 4 (36.4%). All DCIS recurrences were ER- as opposed to IDC recurrences, all of which expressed ER receptors. Patients who developed a recurrence underwent a lumpectomy 90.9% of the time for their initial resection, compared with 56.2% of patients with non-recurrent DCIS. We next evaluated the use of adjuvant RT, RT dose, tumor grade, size, presence of necrosis, and width of surgical margins as predictors of recurrence. Neither rates of RT administration, nor the RT dose were significantly different between the patients who developed recurrent disease versus those who did not. There was a trend toward higher recurrence for patients with high grade DCIS (grade 3) and presence of necrosis. Other factors (tumor size, presence of necrosis, and width of excision margins) did not predict for recurrence risk in our sample.Contrary to expectations, ER- DCIS recurrence rates were similar to previously reported DCIS recurrence rates. This is in contrast to the well described findings for ER- invasive carcinomas. Future prospective studies are needed to further evaluate the outcomes for this patient population.

T-DM1 Increases the Risk of SRS-Induced Radiation Necrosis in Her2+ Breast Cancer

Stereotactic radiosurgery (SRS) is an important treatment modality in the management of breast cancer-related brain metastases (BrM). Recent research has found Trastuzumab emtansine (T-DM1) to be effective against Her2+ BrM. However, the risk of radionecrosis (RN) with T-DM1 in combination with SRS is unclear. The objective of this study was to investigate factors associated with RN post-SRS in patients with Her2+ BrM.Patients with Her2+ BrM treated with SRS at the Sunnybrook Odette Cancer Centre between 2010 and 2020 were retrospectively identified. The incidence of RN was determined on a lesion-by-lesion basis using serial brain imaging with or without histological confirmation. Clinical factors associated with RN, such as age, RT dose, lesion volume, intracranial location, total number of BrM, along with history of whole brain RT, and T-DM1 treatment were investigated with univariable and multivariable competing risks regression (MVR) using death from any cause as a competing risk factor. A P-value of < 0.05 in MVR following backward selection was considered statistically significant.67 patients with Her2+ BrM (223 lesions) treated with SRS were identified; among them, 21 (31.3%) were treated with T-DM1 post-SRS, including 14 (20.9%) who received T-DM1 within 12 months of SRS. The median follow-up was 15.6 (IQR 5.4-35.3) months. The 1-year, and 2-year risk of RN post-SRS was 6.7% (95% CI 2.7-10.7%), and 15.2% (95% CI 9.2-21.3%), respectively. MVR identified T-DM1 treatment post-SRS (HR 2.5, 95% CI 1.2-5.3, P = 0.02) and RT dose with a biologically effective dose (BED) > 50.4 Gy (HR 2.4, 95% CI 1.1-5.1, P = 0.02) as independent risk factors of RN. Patients treated with T-DM1 and SRS had a 25.2% (95% CI 12.8-37.6%) risk of RN at both 1- and 2-years post-T-DM1. The median time to RN after T-DM1 among the affected was 4.8 (95% CI: 3.8-25.6) months with 80% of all RN cases occurring within 12 months of T-DM1 treatment.This study demonstrates that T-DM1 exposure post-SRS was independently associated with a higher risk of RN in Her2+ BrM patients. The potential side effects of brain-penetrating agents post-SRS merit greater awareness.B. Id Said: None. H. Chen: None. K. Jerzak: Research Grant; Astra Zeneca, Eli Lilly. Consultant; Amgen, AstraZeneca, Apo Biologix, Eli Lilly, Esai, Genomic Health, Knight Therapeutics, Merck, Myriad Genetics Inc, Pfizer, Roche, Novartis, Purdue Pharma. S.D. Myrehaug: Advisory Board; Novartis AG.C. Tseng: Consultant; Sanofi. Travel Expenses; Elekta. Member; Elekta MR-LINAC.J. Detsky: None. Z.A. Husain: None. A. Sahgal: Research Grant; Elekta AB. Honoraria; Elekta AB, Varian, BrainLAB, Medtronic Kyphon. Consultant; Varian. Travel Expenses; Elekta AB, Varian. H. Soliman: None.

Phase Ib Study of TAS-102 Plus Radiation Therapy for the Treatment of the Liver in Patients With Hepatic Metastases From Colorectal Cancer

SBRT for liver metastases has emerged as a viable option for treatment of unresectable liver metastases. Among patients with colorectal cancer, however, recent phase II data demonstrated a 1-year local control of 60%, suggesting room for improvement and need for novel strategies to enhance radiosensitivity. TAS 102, an orally administered combination of trifluridine and tipiracil hydrochloride, is an FDA approved regimen for refractor metastatic colorectal cancer. In this study, we evaluated TAS-102 as a radiosensitizer with the goal of improving the efficacy of radiation therapy. In this current abstract, we report the results of the Phase IB study.Patients were enrolled on an investigator-initiated, industry sponsored, prospective, single arm study (NCT03223779). Key eligibility included: histologically confirmed diagnosis of colorectal cancer with 1-4 liver metastases which are deemed unresectable, at least 1 lesion measuring ≥ 1 cm, ECOG PS 0-1, age 18+, and life expectancy > 3 months. Prior treatment including TACE, RFA, and chemotherapy or targeted agents was allowed after a 3-week washout. Prior liver directed RT, including SIRT, was not permitted. Pts were treated with liver RT in 5-6 fractions, delivered 2-4 fractions per week, with RT dose determined by Veff (30-50 Gy in 5 fractions, or 31.8-54 Gy in 6 fractions). TAS 102 dosing occurs on days 1-5 and 8-12. Patients were treated on a 3+3 dose escalation study design, with a starting dose of 20 mg/m2. Dose Limiting Toxicity (DLT) was defined as therapy-related diarrhea, neutropenia, nausea/vomiting, elevation of LFT's, skin toxicity, pain or thrombocytopenia deemed grade ≥ 3. The primary endpoint of the phase Ib component is to determine the maximum tolerated dose (MTD) of TAS-102 when given with SBRT to patients with hepatic metastases from colorectal cancer.From October 2017 to December 2020, 12 patients were enrolled. Median age was 63.5 (range: 32-88), and 7 pts were male (58%). Median RT dose was 50 Gy. On dose level 1 (20 mg/m2 BID), 3 patients were enrolled, none of whom experienced a dose limiting toxicity (DLT). Three patients were enrolled on dose level 2 (25 mg/m2 BID). Two patients completed treatment per protocol, however, the third patient was treated at a reduced dose, on dose level 1, due to elevated bilirubin on C1D1 prior to treatment start and safety concerns. Per protocol design, a fourth patient was enrolled on dose level 2 without toxicity. The third cohort (30 mg/m2 BID) has enrolled 5 patients; 3 have completed treatment as planned, and 2 stopped drug early due to diarrhea (n = 1) and thrombocytopenia (n = 1), both unrelated to study treatment. Of 12 patients, 2 have completed active follow-up, 3 are active in follow-up, and 7 have died. Per protocol design, one more patient is to be enrolled in dose level 3 prior to opening the Phase II portion.In our phase IB study, the MTD dose of TAS-102 with concurrent liver RT is expected to be 30 mg/m2. A phase II study is subsequently planned.

A Population-Based Assessment of Local Therapy for De Novo Oligometastatic Urothelial Carcinoma of the Bladder

<h3>Purpose/Objective(s)</h3> The management of oligometastatic bladder cancer is unclear. Prior data implies site and burden of metastases vary in prognoses. This study evaluates treatment trends, examines the effect of local therapy on survival, and explores if immunotherapy influences outcomes in patients with de novo oligometastatic bladder urothelial carcinoma. <h3>Materials/Methods</h3> A retrospective analysis of the National Cancer Database (NCDB) was performed by identifying bladder urothelial carcinoma patients with metastases (M1 stage) at diagnosis between 2004 and 2016. Local therapy was classified as high-intensity [HT] (i.e., definitive surgery, radiation [RT] dose > 50 Gy) or low-intensity [LT] (i.e., non-definitive surgery, RT dose < 50 Gy). Chemotherapy (CT) was classified relative to local therapy as cytoreductive or consolidative. Metastatic burden was determined by cumulative summation of number of metastatic sites involved (i.e., brain, bone, liver, and lung). Clinicopathologic characteristics were analyzed by descriptive statistics and a Chi-square test was used for comparisons across metastatic disease burden. Univariable (UVA) Kaplan-Meier analysis was used to estimate overall survival (OS). A multivariable Cox regression model was used to estimate the risk of poor survival by treatment modality. Also, effect-modification was assessed between treatment intensity and systemic therapy type. <h3>Results</h3> A total of 11,998 patients were identified with metastases at diagnosis. The median age was 72 years (IQR: 62-80), the majority were Caucasian (87.5%) and male (71.2%). The median follow-up time was 5.5 months (IQR: 2.27-12.62). Patients were treated with definitive surgery (n = 849; 7.1%), perioperative CT (n = 404; 3.4%), CT alone (n = 4,030; 33.6%), RT alone (n = 1,026; 8.6%), CTRT (n = 1,451; 12.1%) or no therapy (n = 3,343; 33.6%). HT and LT were given to 1,083 (9%) and 8,867 (73.9%) patients, respectively. Differences were noted in median OS among treatment groups, such as perioperative CT (OS 16.4 months) or CTRT (> 50 Gy) (12.4 months); <i>P</i> < 0.001. HT vs LT improved OS (10.2 vs 5.7 months; <i>P</i> < 0.001). Consolidative vs cytoreductive therapy improved OS (<i>P</i> < 0.001), but within HT/LT comparisons, sequencing was only significant in HT (16.5 vs 12.7 months; <i>P</i> < 0.001), which was confirmed by interaction analysis. A total of 4,315 patients had site-specific data: bone (n = 1,486), lung (n = 1,175), liver (n = 525) and brain (n = 70). Differences were noted in OS between sites (<i>P</i> < 0.001) with liver and brain having the worst OS. Metastatic burden was also associated with OS (<i>P</i> < 0.001). Immunotherapy was given to 174 patients, which improved OS (12.2 vs 5.7 months; <i>P</i> < 0.001), was independent of metastatic burden, and was associated with 41% reduction in mortality (HR: 0.59, 95% CI: 0.49-0.69; <i>P</i> < 0.001). <h3>Conclusion</h3> This population-based study suggests local aggressive therapy, either surgical or RT (> 50 Gy) is associated with an improved OS benefit in patients with de novo metastatic bladder urothelial carcinoma.

Disease Outcomes Following Low-Dose Radiotherapy vs. Moderate-Dose Radiotherapy for Orbital Low Grade Non-Hodgkin Lymphoma

Orbital low grade non-Hodgkin Lymphomas (LGNHLs) are a common tumor of the ocular adnexa. Courses of low-dose radiotherapy (LDRT), previously defined as 2 Gray (Gy) x 2 fractions, have resulted in excellent short-term outcomes for orbital LGNHLs. Recent data, however, suggests that higher doses are associated with improvements in response rates and progression free survival. RT is a proven treatment modality for this entity, but no prior data exists comparing outcomes following LDRT to moderate-dose RT (MDRT, RT dose > 4 Gy). Herein, we compare outcomes including overall response rates (ORR), local control (LC) and overall survival (OS) for patients treated with LDRT vs MDRT.We reviewed 38 consecutive courses of RT for 36 patients treated for orbital LGNHL at a single institution. Bilateral disease was present in 15 patients. Nine patients had advanced stage disease or secondary orbital lymphoma following systemic dissemination. Indolent histologies included marginal zone lymphoma (20 patients), follicular lymphoma (11 patients), and mantle cell lymphoma (MCL, 5 patients). ORR were recorded according to Deauville or RECIST criteria with a response characterized as a complete response (CR) or partial response. Time to orbital recurrence (TTOR) and OS were estimated with the Kaplan-Meier (KM) method from start of RT to event or last follow-up. Univariate and multivariate Cox regression analysis was performed for characteristics associated with the studied outcomes. RT toxicity was graded per CTCAEv5.Median follow-up time for all patients was 29 months (m) (range, 4-129m) and median MDRT dose used was 24 Gy (range 21-36 Gy) in 1.5-2 Gy fractions. LDRT was delivered for 14 courses and MDRT for 24 courses. Advanced stage (odds ratio (OR) 7, P = 0.021) and year of RT ≥2016 (OR 24, P = 0.008) were associated with increased use of LDRT as compared to MDRT. Acute grade 1 (G1) and G2 RT toxicities occurred following 22 (58%) and 5 (13%) courses, respectively. No ≥G3 acute toxicities occurred. Late toxicities included 6 patients with G1 dry eye (4 MDRT, 2 LDRT), 3 patients with G2 dry eye (3 MDRT) and one patient with a G1 cataract (1 MDRT). ORR were 100% (CR 50%) and 87.5% (CR 58.3%) following LDRT and MDRT, respectively. No evaluated characteristics, including the use of LDRT, were significantly associated with inferior ORR, TTOR or OS. LC at 2 years was 100% and 95% for the LDRT and MDRT groups, respectively.RT for orbital LGNHL is associated with excellent outcomes in terms of response rates and local control. Due to the exquisite radiosensitivity of orbital LGNHL, LDRT produces similar response rates and TTOR as compared to more protracted RT courses. Present data suggests that LDRT should be considered for patients with orbital LGNHL; however, further multi-center studies with larger patient numbers are warranted to show significant associations.

Palliative Radiotherapy for Nonagenarians: A 5-Year Retrospective Analysis

Nonagenarians often present with advanced stage malignancies and complex prior treatment courses. Additionally, the fragility of this patient population can significantly limit surgical or systemic treatment options. Palliative radiotherapy is often offered in these challenging cases, however there is scarce data to help guide clinicians on which select patients may be most appropriate for radiotherapy versus other comfort care measures.A retrospective analysis was performed evaluating all patients from September 2015 to December 2020 who underwent palliative radiotherapy and were ≥ 90 years old at the time of initial treatment. Data pertaining to patient demographics, radiation course details, and survival outcomes were compiled and analyzed using descriptive statistics.35 patients were treated with palliative radiation therapy. Median age 92 (range 90-100). The median ECOG was 1 (range 0-4) and seven patients (20%) had an ECOG of 3-4. Only one patient (2.9%) had received radiotherapy prior to age 90 (8 Gy in 1 fraction). Median number of fractions for all courses was five fractions. Median follow up was 4.6 months. 17 patients (48.6%) presented with symptomatic distant metastases, including 16 for bone metastasis (94.1%) and one for painful right inguinal lymphadenopathy (37.5 Gy in 15 fractions). RT dose for osseous lesions included 6-8 Gy in 1 fraction (n = 10) and 20 Gy in 5 fractions (n = 6). The one month and three-month overall survival for distant palliation was 94.1% and 76.5%, respectively. Seven patients died, all due to their cancer. 18 patients (51.4%) underwent palliative radiotherapy for symptomatic local disease. Median RT dose was 30 Gy in 10 fractions (range, 8-45 Gy in 1-25 fractions). The most common primary anatomic site of progression was gastrointestinal (38.9%), including gastric (2), colorectal (4), and pancreatic (1) malignancies. 10 patients (55.5%) were Stage IV at presentation. Among the 8 patients with stage I-III cancer, four had irretractable gastrointestinal bleeding, three refused definitive treatment, and one presented with non-obstructive painful inoperable colon cancer. The one month and three-month overall survival was 72.2% and 61.1% for local palliation cohort. Six patients died of their cancer, while one patient died of cardiovascular comorbidities.Nonagenarians tolerate palliative radiotherapy for distant metastases and locally progressive disease with over 70% of all patients surviving at least three months. Despite their age, radiotherapy should continue to be considered as palliative treatment for nonagenarians.

De-Intensified (DI) IMPT vs. IMRT(Chemo) for HPV-Associated Oropharynx Cancer (HPV-OPC): Initial Quality of Life (QOL) Results From a Prospective, Multi-Institutional Trial

To compare patient-reported QOL/symptoms between DI IMPT(chemo) and IMRT(chemo) for HPV-OPC.LCCC1612 is a multi-institutional phase II trial of DI RT(chemo) using 60 Gy/30 fx in 6 wk with weekly concurrent cisplatin, 30 mg/m2 for HPV-OPC. Eligible patients (AJCC 8 ed, T0-3, N0-2, M0, p16+, regardless of smoking history) received IMPT at one participating center. T0-2, N1 (single node, < 3 cm) received RT alone. ≥10 pk-y smokers underwent p53 mutation analysis, and only those with wild-type p53 received DI RT(chemo). The IMPT cohort (initial 25 patients with 1y f/u) were matched (2:1) to a randomly selected IMRT cohort using the following: T-class, N-class, and uni- vs. bi-lateral neck RT. QOL/symptoms assessed by EORTC QLQ30, HN35, and EAT-10 were compared at baseline, endRT, 3, 6, and 12 mo. Differences of ≥10 in QLQ30 and HN35 (range, 0-100) and ≥3 in EAT-10 (range, 0-40) were considered clinically relevant.The IMRT cohort consisted of 46 matches (only 1:1 available for 4 IMPT pts). There were no significant differences between non-matched variables (RT dose, chemo, age, gender, smoking history, or primary site). 1-yr PFS was comparable (IMPT, 92%; IMRT, 93%). Only 2/25 (8%) IMPT and 18/46 (39%) IMRT patients required short-term feeding tubes. Both cohorts reported excellent QOL/symptom scores with worse mean scores at end of RT, which returned to baseline by 3 mo for most patients with some exceptions such as dry mouth, sticky saliva, and sensory changes. IMPT resulted in higher (better) mean scores for QLQ30 Global QOL at endRT (55.8/45.8), and role function at endRT (60.1/43.6) and 3 mo (91.7/80.4). Several HN35 mean symptom scores were lower (better) after IMPT including fatigue at endRT (49.3/60.4) and 3 mo (17.2/31.6); appetite loss at 3 mo (16.7/34.8), 6 mo (13.9/27.8), and 12 mo (5.8/16.7); impaired social eating at 3 mo (14.0/30.2) and 6 mo (11.1/22.8); coughing at endRT (29.0/43.2) and 6 mo (15.3/25.6); and feeding tube use at endRT (4.3/34.1) and 3 mo (4.5/15.6). IMPT patients reported less dysphagia with lower mean EAT-10 scores at 3 mo (5.8/10.0) and 6 mo (4.5/8). Narcotic use was higher with IMPT than IMRT at end RT and 3 mo without a difference in pain scores. There was no difference in financial difficulties despite the added costs with proton therapy.DI IMPT(chemo) and IMRT(chemo) resulted in favorable patient-reported QOL/symptoms with most patients reporting return to baseline QOL/symptom scores by 3 mo with some exceptions. DI IMPT(chemo) resulted in very low rate of feeding tube use and less swallowing/eating-related symptoms compared with IMRT(chemo) using independently validated instruments. Additional data and long-term follow-up will be needed to validate these findings and confirm the long-term safety/efficacy of DI RT(chemo).

Concurrent Radiation Therapy With the Antibody-Drug Conjugates Brentuximab Vedotin and Polatuzumab Vedotin

Brentuximab vedotin (BV) and polatuzumab vedotin (PV) are antibody-drug conjugates targeting CD30 and CD79B, respectively, approved for the treatment of select T- and B-cell lymphomas. Safety data to inform the use of concurrent radiation therapy (CRT) with BV or PV is lacking.We retrospectively reviewed 31 patients (pts) who received CRT with BV or PV from 5/2018 to 1/2021. We defined CRT as infusion within 3 weeks prior to or concurrent with RT. Timing of toxicity (CTCAE v5.0) was classified as pre-RT (within 1 month prior to RT), acute (start to 1 month post-RT), and subacute (2-3 months following RT), censored at subsequent systemic therapy. Statistics were performed using Mann-Whitney U and Chi-squared tests.Of 31 pts, 20 (65%) received BV and 11 (35%) received PV. Median age at CRT was 55 (range 27-88), and 14 pts were female (45%). 26 pts (84%) had stage III-IV disease at the time of CRT. The most common diagnoses were mycosis fungoides (12 pts, 39%; 7 with large cell transformation) and diffuse large B cell lymphoma (10 pts, 32%). Pts received a median of 4 lines of prior systemic therapy (range 0-8). 22 pts received prior RT courses (median 1, range 1-6). Fourteen pts received combination regimens with BV or PV: bendamustine and rituximab (R) (5, 16%); cyclophosphamide (C) (± R) (3, 10%); R alone (5, 16%); and C with doxorubicin (1, 3%). Eleven pts (35%) were treated with electrons targeting skin, with a median dose of 12 Gy (range 4-32). Twenty pts (65%) were treated with photons to 32 sites, with a median dose of 25 Gy (range 9-44); treatment sites included the spine (14 pts, 45%), abdomen/pelvis (9 pts, 29%), and brain (3 pts, 10%). Median percent bone marrow (BM) treated was 6.6 (range 0-18.3). The rate of grade 2 or higher (G2+) hematologic toxicity (HT) was 45% (14/31) pre-CRT vs. 79% (23/29) in the acute setting (P = 0.044) and 71% (10/14) in the subacute setting (P = 0.29). There was no significant change in acute or subacute pain, fatigue, diarrhea, neuropathy, or hepatotoxicity following CRT. Acute G2+ HT was associated with pre-RT G2+ HT (P = 0.019) and more lines of prior systemic therapy (P = 0.011). Percentage of BM irradiated was not significantly associated with acute G2+ HT (P = 0.09). Age, concurrent chemotherapy with BV or PV, prior RT courses, RT dose, and RT modality were not associated with G2+ HT. Six pts (19%) were bridged to stem cell transplant at a median of 26 days (IQR 16-52). 12 patients (39%) received subsequent systemic therapy for progression at a median of 81 days (IQR 25-87). Median time to progression or last follow-up was 72 days (IQR 20-113). At last follow-up, 18 pts (58%) were deceased; median overall survival from CRT was 177 days (95% CI 92-263).CRT with BV or PV was overall well tolerated. We observed HT, particularly in patients with cytopenias prior to RT. Care should be taken during RT planning to reduce this risk if possible.

Low Dose to White Matter Predicts Attention and Processing Speed Decline After Fractionated Brain RT

<h3>Purpose/Objective(s)</h3> Attention and processing speed, an important neurocognitive function, is subserved in the brain by critical white matter (WM): the corpus callosum (CC) and intra-hemispheric white matter tracts (IHWM). We sought to characterize the dose-response relationship of these structures with decline in attention/processing speed at 6 months post-RT in patients with primary brain tumors, with particular attention to low doses. <h3>Materials/Methods</h3> On a prospective trial, 52 primary brain tumor patients receiving fractionated brain RT underwent volumetric MRI, diffusion tensor imaging, and neurocognitive assessments (for processing speed: Delis-Kaplan Executive Function System Trail Making (D-KEFS-TM) Number Sequencing (TM-NS), D-KEFS-TM Letter Sequencing (TM-LS), and Weschler Adult Intelligence Scale (WAIS-IV) Coding; for attention: D-KEFS-TM Visual Scanning (TM-VS) test and WAIS-IV Digit Span Digits Forward (DF) test. Reliable change indices were calculated and adjusted for practice effects (RCI-PE), with decrease in RCI-PE scored as decline. Regions of interest (ROIs) were autosegmented using open source software and atlas-based tractography, including: CC, all WM w/wo CC, total IHWM without CC, and right/left IHWM without CC. Censoring masks excluded tumor, surgical cavity, scarring, and edema. Planning CTs were co-registered to MRIs to extract DVH parameters for each ROI, including V10 Gy and V20 Gy. Univariate logistic regressions were used to test for dosimetric predictors of decline. <h3>Results</h3> Median age was 47y. Most patients (61.5%) had gliomas. Median prescription RT dose was 59.4 Gy. At baseline and 6 months, 37-43 patients completed the neurocognitive assessments, with 61-78% showing decline. Several significant associations between increasing relative volumes exposed to low dose and decline were seen in all assessments except TM-NS (Table). Investigation of mean and maximum dose parameters yielded similar results. <h3>Conclusion</h3> While maximum dose is typically considered the most relevant dosimetric parameter for toxicity endpoints in the brain, we also detected several significant logistic relationships between V10 and V20 to more diffuse white matter networks (CC and IHWM) and decline in attention and processing speed post-RT. Minimization of low dose bath, whether by planning optimization or use of more conformal modalities like protons, may be clinically relevant for preservation of these critical neurocognitive functions.

Chemoradiation vs. Radiation Alone in the Management of Inoperable cT1-T2N1 Non-Small Cell Lung Cancer, a Propensity-Weighted Hospital Database Analysis

<h3>Purpose/Objective(s)</h3> Lobectomy followed by adjuvant chemotherapy is the standard of care for patients with clinically T1-T2N1 non-small cell lung cancer (NSCLC). However, the optimal treatment of patients who cannot undergo or refuse to undergo surgical resection is controversial. Currently, NCCN guidelines recommend concurrent chemoradiation; however, limited evidence exists to substantiate this recommendation for this particular patient population. Many groups advocate for radiation alone with standard or hypofractionated approaches. We hypothesized that concurrent chemoradiation would be associated with longer overall survival (OS) compared to hypofractionated or conventionally fractionated radiation. <h3>Materials/Methods</h3> We queried the National Cancer Database (NCDB) for patients with cT1-T2N1M0 NSCLC treated non-surgically with definitive radiation or concurrent chemoradiation between 2004 and 2016. We further restricted our cohort to patients receiving RT doses with an EQD₂ ≥ 58.4 Gy and > 5 fractions. Patients were divided into four treatment groups: standard fractionated radiation (SFRT), hypofractionated radiation (HFRT), standard fractionated chemoradiation (SFRT+CT), and hypofractionated chemoradiation (HFRT+CT). Chemoradiation was defined as chemotherapy and radiation with start dates within 30 days. To address confounding by indication, inverse probability of treatment weights (IPTW) were constructed regressing sociodemographic, clinical, and facility characteristics on treatment group in a multinomial regression model. Weighted Cox proportional hazard regression models were then used to evaluate the relative hazard of death with SFRT set as the referent treatment group. <h3>Results</h3> A total of 2,534 patients met inclusion criteria and of these 2,200 patients (57,462.83 person-months) had complete data for all confounders and were included in the analytic sample. Of the 2,200 patients 26.6% received SFRT, 7% received HFRT, 62.1% received SFRT+CT, and 4.2% received HFRT+CT. The median EQD₂ (IQR) were: SFRT 66 Gy (60-68), HFRT 66.7 Gy (62.5-71.9), SFRT+CT 65.5 Gy (60-66), and HFRT+CT 67.6 Gy (65.1-72.3). 27% of patients were still alive 36 months after the initiation of RT (17.3% of SFRT, 20.3% of HFRT, 33.2% of SFRT+CT, and 21.8% of HFRT+CT). After IPTW propensity weighting, the probability of death at 3 years was compared between the treatment groups and only SFRT+CT was associated with longer OS. Compared with SFRT, the hazard ratio for all-cause mortality for those treated with SFRT+CT was 0.67 (95% CI: 0.57-0.75), for HFRT was 0.86 (95% CI: 0.61-1.06), and for HFRT+CT was 0.81 (95% CI 0.61-1.06). <h3>Conclusion</h3> To our knowledge, this is the first large database propensity weighted analysis of patients with cT1-T2N1M0 NSCLC managed non-surgically with definitive radiation or chemoradiation. In this group, treatment with SFRT+CT is associated with longer OS relative to treatment with radiation alone.

VMAT Focal Boost to MRI-Defined Intraprostatic Lesion in Localized Prostate Cancer: Results of a Phase II Trial

Advances in the identification of the dominant intraprostatic lesion (DIL) with multi-parametric magnetic resonance imaging (mpMRI) have enabled selective focal radiation dose intensification. The aim of this prospective phase II trial was to determine the PSA and mpMRI response, toxicity and quality of life (QOL) in men with localized prostate cancer (PCa) treated with image-guided focal boost to the DIL. We report early results on local and biological control and toxicity. The hypothesis is that differential boosting with focal dose escalation to an mpMRI defined DIL is associated with a higher clinical control without a significant increase in toxicity.From February 2017 to January 2020, 30 patients with intermediate and high risk PCa with a visible DIL identified on mpMRI were included in a prospective phase II trial. Matching point registration of planning TC and T2-weighted, diffusion-weighted and a gradient recalled echo (GRE) MRI images made in treatment position was used for prostate and DIL delineation. Treatment consisted on 35 daily fractions of 2.17 Gy with a concomitant focal boost to the intraprostatic nodule of 2.43 Gy using VMAT (volumetric modulated arc therapy) and IGRT (image guided radiation therapy) with daily CBCT (cone beam CT) and intraprostatic fiducial markers. Androgen derivation therapy (ADT) was allowed for unfavorable intermediate and high-risk tumors. Biochemical failure was analyzed using nadir+2 ng/ml criteria and local control using mpMRI evaluation at 6 and 9 months following RT. Acute and late toxicity were defined according to CTCAE v4.0 and RTOG/EORTC scales and QoL was assessed using IPSS, EPIC short-form and UCLA-PCI questionnaires.Dose intensification was feasible in the 30 patients. The median prostate dose was 77.6 Gy (IQR 77.3-78.1) and the median DIL RT dose was 85.2 Gy (IQR 85.0-85.4). With a median follow up of 33 moths (IQR 24.5 - 41.5), all 30 patients remain free of biochemical relapse. A mpMRI complete response was observed in 23 patients during the first post-treatment evaluation performed at 6 months. The remaining 7 patients achieved a complete response in the second mpMRI made at 9 months. Six out of 30 (20%) patients presented acute grade 2 urinary toxicity with no grade 3 acute complications. Acute rectal toxicity was only found in 2 (6.6%) patients (both grade 1). Only late grade 1 urinary (3 cases) and rectal (3 cases) complications were observed, with no grade 2 or more late toxicity.Although preliminary, the present results show that focal dose escalation RT using mpMRI guided VMAT technique is associated with an encouraging local and biochemical control and a safe toxicity profile. This trial was registered on ClinicalTrials.gov, NCT03030625.

Radiation for Anorectal Cancers in Patients With a History of Prostate Radiation Therapy

RT for rectal and anal cancer after prostate cancer RT is usually avoided due to fear of complications, and data on this topic is scarce. Our aim was to evaluate outcomes and toxicity associated with RT in this group of patients.We conducted a single institution retrospective study of patients treated with RT for rectal or anal cancer after prior prostate RT from 1/1/1995 - 8/1/2019. Acute and long-term toxicities were collected. Treatment plans were extracted to assess doses to organs at risk and target coverage. Wilcoxon rank sum test was used for correlation between dosimetry and toxicities. Estimated cumulative incidence was used for local progression.We identified 29 patients who received RT after prostate cancer RT, 19 with rectal cancer and 10 with anal cancer. None of those patients had metastatic disease. Prior prostate RT was delivered using low dose rate brachytherapy (LDR) in 15/29 patients with a median dose of 145 Gy (144-160), external beam RT (EBRT) in 10 patients with 79.2Gy/44 or 81Gy/45 fractions (fr), and EBRT + LDR in 4 patients with 50.4/28 + 80-110 Gy I-125 or Pd-103 LDR. RT for rectal cancer was delivered most commonly with 50.4Gy/28 fr or 1.5 Gy twice daily fractionation to 30-45 Gy (53% of patients). The most commonly used RT dose for anal cancer was 50Gy/25 fr. Brachytherapy was used in 6 (21%) patients: as a boost after EBRT in 2 patients with anal cancer and alone in 4 rectal cancer patients. Median interval between prostate and anorectal RT was 134 months (6-303). 68% and 80% of rectal and anal cancer patients got concurrent chemotherapy. Table 1 summarizes toxicities associated with anorectal re-RT. Two patients developed fistulas, one was urinary cutaneous after prostate LDR and 45Gy/25fr for rectal cancer, and the other recto vesicular after prostate LDR and 50Gy/25fr for anal cancer; both repaired by extensive surgery. Both patients had more than 10 years between the two RT courses. In 21 patients with available dosimetry, coverage was adequate with a GTV V100% of 98% for rectal cancer patients and 96% for anal cancer patients. There was no significant correlation between toxicities and dosimetric values probably due to the small sample size. The estimated 5-year local progression incidence for all patients was 22%: 11% for rectal cancer, and 4% for anal cancer patients.RT of anorectal cancer after prior prostate cancer RT is feasible but poses a risk of fistulae. Further studies, possibly using proton therapy and/or rectal hydrogel spacers, are needed to further establish the feasibility of RT in this context, decrease toxicity, and improve outcomes.

Multi-Institutional Outcomes of Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy (SMART) With Median Biologically Effective Dose of 100 Gy10 for Oligometastases

<h3>Purpose/Objective(s)</h3> Randomized data show an overall survival (OS) benefit of stereotactic ablative body radiation therapy (SABR) in addition to chemotherapy (CT) in selected patients with oligometastasis (OM). While ablative dose can be safely delivered to some lesions, others in proximity to some organs at risk (OARs) such as bowel may be treated with non-ablative dose to limit toxicity. Stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting OARs, which may improve long-term disease control. <h3>Materials/Methods</h3> The RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Patients with < 3 months (mo.) follow-up after SMART were excluded. Local control (LC), freedom from distant progression (FFDP), progression free survival (PFS), and OS were estimated using the Kaplan-Meier method. LC was evaluated using RECIST 1.1 criteria. Acute toxicity was defined as within 90 days of SMART and evaluated using CTCAE v4 criteria. <h3>Results</h3> 101 patients with 114 OM lesions were treated on a 0.35T-MR Linac at 2 institutions between 2018-2020. Median age was 62 years (range 23-89), and 99% were ECOG 0-1 performance status. The primary tumor was definitively managed in 34.7%, most commonly in the lung (30.7%), colon/rectum (22.8%), cervix/uterus/ovary (13.9%), or breast (5.9%). About 50% received CT for OM prior to SMART. SMART was delivered to 1 (87.7%) or 2 (10.5%) lesions, mostly involving abdominal/pelvic lymph nodes (40.4%), liver (17.5%), lung (17.5%), or adrenal gland (11.4%). All were treated without fiducial markers and with real-time tissue tracking and automated beam gating, typically in breath hold. The median prescribed RT dose was 45 Gy (range 24-60Gy) in a median 5 fractions (range 3-15). The median biologically effective dose (BED₁₀) was 100 Gy₁₀ (range 41.4-180). The median PTV was 14.5 cm³ (range 1.5-567.8). Median follow-up was 10 months (range 3-25) from SMART. One-year LC, FFDP, PFS, and OS were 88%, 38.2%, 36.1%, and 90.6%, respectively. Median PFS and OS were 9 months and not reached, respectively. No acute/late grade 3+ toxicities were recorded. <h3>Conclusion</h3> To our knowledge, this represents the largest analysis of SMART for OM. A median prescribed BED₁₀ of 100 Gy₁₀ resulted in excellent early LC and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. These outcomes are noteworthy given the predominance of OM, especially LNs, treated with dose escalation in proximity to gastrointestinal OARs; such lesions are notably underrepresented in SABR OM trials. Prospective evaluation of dose-escalated SMART for OM is warranted.

Long-Term Patient-Reported Quality of Life and Functional Outcomes After Chemoradiation Using Intensity Modulated Radiotherapy for Anal Cancer

Few studies have long-term follow-up assessing patient-reported outcomes (PROs) after intensity-modulated radiation therapy (IMRT)-based chemoradiation (CRT) for squamous cell carcinoma of the anus (SCCA). There is poor agreement between physician-graded toxicity and PROs regarding quality of life (QOL) in patients with SCCA. Therefore, we surveyed SCCA survivors ≥ 2 years out from CRT with validated PRO instruments assessing bowel, bladder, and sexual function.We identified 248 patients with SCCA treated with definitive IMRT-based CRT at a large tertiary cancer center from 2010-2018, who were alive and without recurrence. Patients were asked to complete five PRO instruments: Fecal Incontinence QOL Scale (FIQOL), Low Anterior Resection Syndrome Score (LARS), International Consultation on Incontinence Questionnaire (ICIQ), male and female lower urinary tract symptoms (MLUTS and FLUTS, respectively), International Index of Erectile Function (IIEF), and Female Sexual Function Index (FSFI). FIQOL, LARS, IIEF, and FSFI scores were dichotomized and logistic regression used to identify predictors of QOL scores.One hundred eight (44%) patients completed the PROs. Respondents' median [interquartile range, (IQR)] age was 66 [59-72] years, 80% were female, and 95% were white. Median [IQR] gross tumor volume (GTV) was 45 [27-71] cc; dose to GTV was 50 Gray (Gy), 54 Gy and 58 Gy in 25%, 53%, and 22%, respectively. Median [IQR] time from CRT was 51 [37-84] months. Median [IQR] FIQOL score was 14.3/20 [11.2-16.1]; higher is better. Larger GTV size (OR 0.99; P = 0.03) was associated with lower FIQOL score. Sixty-one (56%) patients met major LARS criteria. There was a trend towards a higher incidence of major LARS with GTV dose ≥ 54 Gy (OR 2.39; P = 0.08). Men had median [IQR] ICIQ MLUTS voiding and incontinence scores of 5/20 [2-6] and 1/24 [1-3], respectively. Women had median [IQR] ICIQ FLUTS voiding and incontinence scores of 1/12 [1-3] and 5/20 [3-8], respectively; higher is worse. Fifty-nine (55%) patients reported being sexually active in the last month. Men had a median [IQR] IIEF score of 14/25 [6-19]; higher is better. Only age (OR 1.17; P = 0.04) was significantly associated with IIEF ≤ 11 (moderate or severe ED). Women had a median [IQR] FSFI score of 20.2/26 [13.6-24.9]; higher is better. Age < 65 was associated with sexual dysfunction, defined as FSFI < 26.55 (OR, 5.5; P = 0.04). Forty (37%) patients disagreed or strongly disagreed that they were prepared for long-term side effects. Seventy (65%) patients agreed or strongly agreed that educational materials would have been helpful.SCCA survivors experience significant long-term bowel and sexual toxicities from modern CRT. Larger tumors and higher RT doses may be associated with worse function. Interventions to reduce toxicities and improve patient education are needed.

Salvage Radiotherapy for Relapsed/Refractory Non‐Hodgkin Lymphomas Following CD19 Chimeric Antigen Receptor T-Cell (CART) Therapy

<h3>Purpose/Objective(s)</h3> CD19-directed CART therapy has emerged as a promising treatment for relapsed/refractory non-Hodgkin lymphoma. However, sustained efficacy is limited with durable complete response rates of 40% (Schuster & Locke, 2019). Salvage radiotherapy (SRT) is potentially an important strategy post‐CART, but current data is limited to one series of 14 patients. <h3>Materials/Methods</h3> We retrospectively analyzed 21 patients who received SRT after commercial CART therapy between 8/2018 and 6/2020. Patients who relapsed after CART were divided into two groups: locoregional disease (LD, all relapsed disease encompassable within an RT field) and advanced disease (AD). SRT was defined as comprehensive (treated all sites of active disease) or focal. Post-SRT in-field objective response rates (ORR) were recorded according to Deauville or RECIST criteria with a response characterized as a complete response or partial response. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Acute RT toxicity was graded by CTCAEv5. <h3>Results</h3> Median time from CART infusion to SRT was 4.0 months (m) (range, 0.6-11.6m). Within the LD group, 8/9 patients were treated with comprehensive SRT (median SRT dose 37.5 Gy, range 8-45 Gy, and number fractions 15, range 2-25 fractions). The in-field ORR was 8/9 (89%). For the AD group, 12/12 patients were treated with focal SRT (median SRT dose 20.8 Gy, range 8-30 Gy, and number fractions 5, range 1-12 fractions). 11/12 AD patients were treated with hypofractionated SRT (≥2.5Gy fractions). Three patients died prior to subsequent imaging with an ORR of 8/9 (89%) for the remaining evaluable patients. Distant progression occurred in 17/18 patients post-SRT (Table). Three-month PFS was 24% for the entire cohort, and 33% and 17% for the LD and AD groups, respectively (<i>P</i> = 0.258). Median OS was 7.4m for the entire cohort, and 21.1m and 2.4m for the LD and AD groups, respectively (<i>P</i> < 0.001). Grade 1 (G1) and G2 acute SRT toxicities occurred in 10 and 4 patients, respectively. No G3 or higher toxicities occurred. <h3>Conclusion</h3> SRT post-CART therapy appears safe (no ≥G3 RT toxicities) in our series. SRT led to an ORR of 89% with only 1 observed local relapse. Patients with LD relapse post-CART had significantly improved survival compared with AD relapse. Unfortunately, prognosis remains poor as 17/18 patients with evaluable imaging progressed outside of the RT field. Thus, prolonged RT courses may not be warranted given the practical inevitability of out of field disease progression. Multi-institutional review of SRT following CART is warranted to further elucidate the impact of RT dose and fractionation on disease outcomes.