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Presence of MYC, BCL2 , and/or BCL6 translocations (i.e., double/triple-hit lymphoma [DHL/THL]) among patients with large cell lymphoma (LCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy. This retrospective, multi-institutional, international cohort included 211 patients with LCL and known DHL/THL status, who received RT in the relapsed/refractory (r/r) setting. Only the first RT course was included. Separate analyses were conducted for curative versus palliative intent. Response was defined as a radiographic or clinical complete or partial response (PR). Primary chemorefractory disease was defined as less than a PR to initial chemotherapy. Predictors for response and local recurrence (LR) were evaluated using Cox regression analysis. LR analyses and estimates were restricted to patients treated with curative intent to ensure adequate follow-up (median 39.6 months among surviving patients). Patients were heavily pretreated prior to RT (25% stem cell transplant, 8.5% CART, 41% >2 lines of therapy); 49% were irradiated with curative intent. Most patients (90% curative, 100% palliative) had macroscopic disease at RT. Response rates were similar among those with versus without DHL/THL pathology: 71.4% vs 81.2% (curative), 54.5% vs 64.7% (palliative). DHL/THL was not associated with response on univariate analysis in either the curative (HR 1.03, 95% CI 0.58-1.84, p=.91) or palliative setting (HR 1.42, 95% CI 0.73-2.76, p=.29). In contrast among patients irradiated with curative intent, presence of DHL/THL pathology was associated with increased LR risk (HR 2.38, 95% CI 1.15-4.92, p=.02), controlling for primary chemorefractory disease and radiation biologically effective dose (BED10). LR at 6 and 12 months was 21% and 30% among non-DHL/THL and 41% and 45% among DHL/THL, respectively. R/R LCL is radioresponsive. Though presence of DHL/THL pathology does not appear to impact RT response , it is associated with increased LR risk, suggesting that it may influence radiation sensitivity. These findings require confirmation in other cohorts. [ABSTRACT FROM AUTHOR]

To report an ILROG multi-institutional analysis of bridging radiotherapy (BRT) prior to CD19-targeting chimeric antigen receptor T-cell (CAR T) therapy for relapsed/refractory aggressive B-cell lymphomas (BCL). Weretrospectively reviewed 115 patients (pts) with diffuse large BCL (n = 101, 88%), primary mediastinal BCL (n = 11, 10%), mantle cell lymphoma (n = 2, 2%), and T-cell/histiocyte rich large BCL (n = 1, 1%) who received BRT prior to commercial CAR T from 2018-2020 across 6 institutions. BRT toxicities were graded per CTCAE v5.0, cytokine release syndrome (CRS) per ASTCT, and immune effector cell-associated neurotoxicity syndrome (ICANS) per either ASTCT or CTCAE v5.0. Progression-free survival (PFS) and overall survival (OS), measured from CAR T infusion, were estimated using the Kaplan-Meier method. PFS was modeled using Cox regression with stepwise variable selection. BRTwas given prior to axicabtagene ciloleucel (axi-cel; n = 82, 71%), tisagenlecleucel (tisa-cel; n = 31, 27%), or brexucabtagene autoleucel (n = 2, 2%). Median age was 62 years with median of two prior lines of therapy. Most pts had advanced stage III/IV disease at leukapheresis (n = 87, 76%), elevated pre-leukapheresis LDH (n = 73, 63%), and bulky disease (n = 55, 50%) (1 lesion ≥7.5 cm). 78 pts (68%) had extranodal disease, 12 (10%) had central nervous system (CNS) involvement, and 36 (31%) had bone involvement. Systemic bridging therapy was given to 42 pts (37%). Median intervals from leukapheresis to BRT start and from BRT completion to CAR T infusion were 5 days (IQR -6, 11) and 12 days (IQR 9, 23), respectively. BRT was delivered to 163 total sites; most commonly the abdomen/pelvis (n = 58, 50%), head/neck (n = 34, 30%), thorax (n = 20, 17%), extremity/soft tissue (n = 20, 17%), and CNS (n = 13, 11%). Median biologically effective dose was 31.3 Gy (IQR 24, 39). Most common regimen was 30 Gy in 10 fractions (n = 27, 17%). 40 pts (35%) received comprehensive BRT (to all active lesions). There were no grade ≥3 BRT toxicities. Grade ≥3 CRS occurred in 9 pts (8%), including 8/82 (10%) after axi-cel and 1/31 (3%) after tisa-cel. Grade ≥3 ICANS occurred in 23 pts (20%), including 22/82 (27%) after axi-cel and 1/31 (3%) after tisa-cel. Median follow up was 26.9 months. 1- and 2-year OS rates were 60% and 49%. 1- and 2-year PFS rates were 41% and 35%. Comprehensive BRT associated with superior PFS (HR 0.34, 95% CI 0.19-0.62, p<0.001) in a multivariable model with age ≥60, ECOG ≥2, advanced stage, CNS disease, pre-leukapheresis LDH, and axi-cel. In this multi-institutional study, pts receiving BRT prior to CAR T therapy for BCL frequently had bulky disease yet experienced favorable PFS and OS. There were no serious toxicities attributable to BRT, and the rates of CRS and ICANS are comparable to those after CAR T alone. Comprehensive BRT associated with superior PFS. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Despite being an integral part of stem cell transplant, the technical aspects of classical total body irradiation (TBI) remain relatively crude. In particular, the implementations of lung and cardiac shielding vary widely between institutions. We hypothesize that the block margins away from anatomical landmarks could substantially alter lung and cardiac dose parameters, and thus affecting the likelihood of TBI-related toxicities such as radiation pneumonitis and late cardiotoxicities. This work seeks to utilize a newly commissioned 3D TBI beam model to determine potential dosimetric effects caused by variations in the choice of shielding parameters to better understand the potential for such detrimental effects.Materials/methods: We commissioned a TBI beam model in a treatment planning system. CT scans of 3 anonymized patients without gross disease are contoured following typical clinical practice. Patients are planned in the classic standing AP/PA at extended distance technique for a total dose of 1200 cGy in 6 fractions to midline at umbilicus level, with 3/6 fractions delivered with lung blocks. Lung blocks are modeled using automated script in the treatment planning system, with varying superior (from clavicles), inferior (from diaphragms), and lateral margins from 0 to 2 cm, as well as cases for which the cardiac silhouette was blocked or unblocked for the study. Dose to lungs and heart were calculated and compared for the following metrics: mean dose, volume receiving 10 Gy (V10 Gy) and 12 Gy (V12 Gy), and point dose behind the blocks.Results: The results showed that the point dose behind the blocks is approximately 75% of prescription dose for all patients, with insignificant changes with varying block margins. The dose off the block center increases rapidly that much of the tissue under the blocks receives 80% to 90% of prescription dose. Similar results are observed for mean lung dose. In contrast, the lung V10 Gy increases by nearly two-fold, from approximately 30% to 60% over the 0 to 2 cm block margin range. The mean heart dose increased by approximately 7.5% when the cardiac silhouette is unblocked, while the cardiac V12 Gy increased by approximately 25%. The mean dose to left anterior descending artery (LAD) increases significantly in the unblocked case, with as much as 43% difference.Conclusion: This work has shown that margins of lung blocks could affect the dose to lungs and heart substantially, despite the indifference that the commonly used point dose parameter, point dose behind the blocks, indicates. A 3D TBI model could provide more dosimetry data to help future studies to correlate TBI-associated toxicity to the heart and lungs. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): In the absence of randomized prospective data, the role of postoperative radiotherapy (PORT) for localized Merkel cell carcinoma (MCC) is controversial with varying practice patterns. Although a majority of patients with resected stage I/II MCC without adverse features may be cured with surgery alone, those with adverse features including head and neck (HN) primary tumors have local recurrence rates of 20% or more without PORT (Takagishi et al. Adv Radiat Oncol, 2016). Extrapolating from our experience demonstrating high rates of local control with single fraction radiotherapy (SFRT) for metastatic MCC (Iyer et al. Cancer Med, 2015), we hypothesized that SFRT (8 Gy) may be effective as PORT to optimize local control for stage I/II MCC with adverse risk features (e.g., HN disease, immunosuppression, recurrent disease, non-oncologic resection, lymphovascular space invasion (LVSI)), especially in patients for whom a conventional RT course may not be feasible.Materials/methods: A single-institution, retrospective review of patients with clinical or pathological stage I/II MCC receiving SFRT (8 Gy) as postoperative treatment (SF-PORT) was completed from a prospectively-enrolled database.Results: Thirty patients (median age 78 years) were identified who received SFRT after wide local excision (n = 24; 80%), Mohs surgery (n = 1; 3%), shave or excisional biopsy only (n = 5; 17%) of the primary. Patients had pathological stage I (n = 15; 50%), clinical stage I (n = 10: 33%), pathological stage II (n = 3; 10%) or clinical stage II (n = 2; 7%) disease. All patients received SF-PORT (8 Gy) at a median of 43 days (range: 14-203) following resection or biopsy. Five patients (4 with HN disease) received SFRT to draining lymph nodes. The majority of patients had HN tumors (77%), LVSI was present in 23%,17% were immunosuppressed and 7% had locally recurrent disease (n = 2). At median follow-up of 11.3 months (range: 3-45.7), no local or in-field recurrences were observed. No local or distant recurrences, MCC specific deaths, or RT related toxicities grade > 1 (CTCAE v5.0) were observed. There were two out-of-field regional nodal recurrences in HN patients who did not receive elective nodal RT.Conclusion: Our early experience demonstrates a high rate of in-field local control in patients with stage I/II MCC with adverse features managed with SF-PORT. This approach warrants further study. [ABSTRACT FROM AUTHOR]