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Background: Select patients with relapsed/refractory aggressive B cell lymphoma may benefit from bridging radiation (bRT) prior to anti-CD19-directed chimeric antigen receptor T cell therapy (CAR-T). Here, we examined patient and treatment factors associated with outcomes and patterns of failure after bRT and CAR-T., Methods: We retrospectively reviewed adults with diffuse large B-cell lymphoma (DLBCL) who received bRT prior to axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel between 11/2017-4/2023. Clinical/treatment characteristics, response, and toxicity were extracted. Survival was modeled using Kaplan-Meier or Cox regression models for events distributed over time, or binary logistic regression for disease response. Fisher's Exact Test or Mann-Whitney U methods were used., Results: Of 51 patients, 25.5% had bulky disease and 64.7% had Stage III/IV disease at the time of RT. Comprehensive bRT alone to all disease sites was delivered to 51% of patients, and 29.4% were additionally bridged with systemic therapy. Median follow-up was 10.3 months (95% CI: 7.7-16.4). Overall response rate (ORR) was 82.4% at 30 days post-CAR-T infusion. Median overall survival (OS) was 22.1 months (6.6-not reached) and the median progression-free survival (PFS) was 7.4 months (5.5-30). OS/PFS were 80% (66-99)/78% (64-87) at 1-year, and 59% (44-71)/54% (40-67) at 2-years, respectively. Comprehensive RT to all sites of disease correlated with improved PFS and OS, p ≤ 0.04. Additionally, ECOG ≥2 and Stage III/IV disease predicted poor OS ( p ≤ 0.02). Disease bulk, IPI ≥3, and non-GCB histology were poor predictors for disease-specific survival (DSS), p <0.05. The latter two, as well as bRT dose of ≤30 Gy predicted worse PFS ( p <0.05). Among patients with advanced stage disease, comprehensive bRT to all sites of disease ( n =10) was not associated with improved OS and PFS compared to focal bRT ( n =23), p >0.17. No difference was seen in bridging RT vs. chemoRT. Twenty-six patients developed relapse (50.9%), of which 46% was in-field. Risk of in-field relapse correlated with bulky disease (OR=7, 95% CI: 1.2-41, p =0.03) and lack of response at 30 day post-CAR-T evaluation (OR=16.8, 95% CI: 1.6-176, p =0.02), but not with bRT dose ( p =0.27)., Conclusion: bRT and CART is a good treatment strategy for select patients with aggressive B cell lymphoma. Comprehensive bRT including all sites of disease is associated with improved outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Manzar, Pinnix, Dudzinski, Marqueen, Cha, Nasr, Yoder, Rooney, Strati, Ahmed, Nze, Nair, Fayad, Wang, Nastoupil, Westin, Flowers, Neelapu, Gunther, Dabaja, Wu and Fang.)

Purpose: The impact of bridging radiation therapy (bRT) for chimeric antigen receptor (CAR) T-cell therapy on absolute lymphocyte count (ALC) kinetics and treatment outcome is unknown., Methods and Materials: We retrospectively reviewed adults with relapsed/refractory aggressive large B cell lymphoma who received bRT before CD-19 CAR-T between November 2017 and April 2023. The change in ALC (ALC Δ RT) was computed by subtracting ALC pre- and post-bRT. Percent bone marrow (%BM) irradiated was calculated by estimating skeletal BM distribution. Progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were modeled via Kaplan-Meier., Results: Fifty-one patients received bRT, of which 13 (25.5%) had bulky disease (≥7.5 cm). The median bRT dose was 30 Gy (range, 4-48 Gy); 26 patients (51%) received ≥30 Gy. Thirty-one patients (61%) received bRT comprehensively to all disease sites. The median cumulative %BM irradiated was 5.05% (range, 0-50%). At a median follow-up of 10.3 months (95% CI, 7.7-16.4), the 1-year OS, PFS, and DSS rates were 80% (95% CI, 66-99), 78% (64-87), and 82% (68-90), respectively. The incidence of grade ≥3 lymphopenia was 33% pre-RT and 68% post-RT, but recovered to 43% at the conditioning chemotherapy timepoint. There was no correlation between post-RT grade ≥3 lymphopenia and the receipt of comprehensive bRT, combined modality bridging, ≥30 Gy bRT, or bRT to ≥15% of BM (all P > .2). Among patients with grade 0-2 lymphopenia pre-RT, increased conversion to grade ≥3 lymphopenia post-RT correlated with comprehensive or ≥30 Gy bRT, but these factors did not impair ALC recovery at conditioning chemotherapy. There was no association between ALC Δ RT or post-RT ALC with 30 or 90 day response (P > .25), DSS, PFS, or OS (P > .3)., Conclusions: Lymphocyte change during bRT is not associated with CAR-T outcomes. Persistent cytopenia risk after bRT is not associated with bRT to ≥30 Gy, ≥15% of BM, or comprehensive coverage. Although bRT can be delivered safely, we urge careful treatment planning when incorporating into pre-CAR-T regimens., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Diffuse large B-cell lymphoma (DLBCL) involving the gastrointestinal (GI) organs is rare, and real-world outcomes after combined modality therapy (CMT) with systemic therapy (ST) and radiotherapy (RT) are not well-characterized, particularly in the contemporary era. We characterized outcomes in a large cohort of GI-DLBCL patients treated with ST alone or CMT., Methods: Patients with GI-DLBCL treated at a single institution were retrospectively reviewed. Kaplan-Meier and Cox regression models estimated survival. Multivariable analyses were conducted using the Cox proportional hazards model., Results: Of 204 patients, gastric involvement was most common (63%). Most presented with early-stage disease (61%). All patients received ST and 65 patients (32%) received RT, 88% as part of first-line CMT. Median dose was 36 Gy (IQR 30.6-39.6) in 18 fractions (IQR 17-22). Median follow-up was 46 months. Five-year overall survival (OS) and progression-free survival (PFS) was 88% and 84%, respectively; complete response (CR) rate was 82%. Improved OS associated with low IPI ( p =0.001), fewer chemotherapy lines ( p <0.001), early stage ( p <0.006), and CR ( p <0.001). Survival did not differ by RT receipt ( p >0.25). Only early stage and CR correlated with improved OS on multivariable analysis. Stomach-directed RT vs. RT to other sites correlated with improved PFS and OS ( p <0.04). Patients with early stage DLBCL treated with CMT in the post-rituximab era had equivalent OS vs. ST alone, even with fewer chemotherapy cycles ( p <0.02; median of 4 with RT vs. 6 cycles without). Fifty patients had bulky disease (≥7.5 cm), of whom 18 (36%) had early stage disease. Among patients with bulky disease, 5 (10%) developed relapse at the initial site of disease bulk. Four of the 5 patients did not receive consolidative radiation. Among these 4 patients, 3 relapsed only in their initial site of bulky disease. Of 191 patients with luminal GI-DLBCL, n =4 (2.1%) developed perforation; only one received RT. Acute Grade 3 toxicities were reported in 41.2% of patients, and 12 (5.8%) patients had late Grade 3 toxicities, 99% attributed to chemotherapy., Conclusion: GI-DLBCL patients have favorable outcomes after CMT with minimal late toxicity. CMT may be offered with abridged systemic regimens with equivalent outcomes. Stomach directed-RT may mitigate relapse risk associated with incomplete disease response or bulky disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Manzar, Cha, Corrigan, Yoder, Schrank, Nasr, Chihara, Castillo, Nair, Jain, Neelapu, Rodriguez, Strati, Nastoupil, Gunther, Dabaja, Pinnix, Wu and Fang.)

Purpose: : Guidelines for early-stage breast cancer allow for radiation therapy (RT) omission after breast conserving surgery among older women, though high utilization of RT persists. This study explored surgeon referral and the effect of a productivity-based bonus metric for radiation oncologists in an academic institution with centralized quality assurance review., Methods and Materials: : We evaluated patients ≥70 years of age treated with breast conserving surgery for estrogen receptor (ER)+ pT1N0 breast cancer at a single tertiary cancer network between 2015 and 2018. The primary outcomes were radiation oncology referral and RT receipt. Covariables included patient and physician characteristics and treatment decisions before versus after productivity metric implementation. Univariable generalized linear effects models explored associations between these outcomes and covariables., Results: : Of 703 patients included, 483 (69%) were referred to radiation oncology and 273 (39%) received RT (among those referred, 57% received RT). No difference in RT receipt pre- versus post-productivity metric implementation was observed ( P  = .57). RT receipt was associated with younger patient age (70-74 years; odds ratio [OR], 2.66; 95% confidence interval [CI], 1.54-4.57) and higher grade (grade 3; OR, 7.75; 95% CI, 3.33-18.07). Initial referral was associated with younger age (70-74; OR, 5.64; 95% CI, 3.37-0.45) and higher performance status (Karnofsky performance status ≥90; OR, 5.34; 95% CI, 2.63-10.83)., Conclusions: : Nonreferral to radiation oncology accounted for half of RT omission but was based on age and Karnofsky performance status, in accordance with guidelines. Lack of radiation oncologist practice change in response to misaligned financial incentives is reassuring, potentially reflecting incentive design and/or centralized quality assurance review. Multi-institutional studies are needed to confirm these findings., (© 2022 The Authors.)