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Dimitri Maamari1 ,* Habib El-Khoury1 ,* Omran Saifi,1 Samar A Muwakkit,2 Nathalie K Zgheib3 1Faculty of Medicine, American University of Beirut, Beirut, Lebanon; 2Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon; 3Department of Pharmacology and Toxicology, American University of Beirut, Faculty of Medicine, Beirut, Lebanon*These authors contributed equally to this workCorrespondence: Samar A Muwakkit; Nathalie K Zgheib Email sm03@aub.edu.lb; nk16@aub.edu.lbAbstract: Despite major advances in the management and high cure rates of childhood acute lymphoblastic leukemia (ALL), patients still suffer from many drug-induced toxicities, sometimes necessitating dose reduction, or halting of cytotoxic drugs with a secondary risk of disease relapse. In addition, investigators have noted significant inter-individual variability in drug toxicities and disease outcomes, hence the role of pharmacogenetics (PGx) in elucidating genetic polymorphisms in candidate genes for the optimization of disease management. In this review, we present the PGx data in association with main toxicities seen in children treated for ALL in addition to efficacy, with a focus on the most plausible germline PGx variants. We then follow with a summary of the highest evidence drug-gene annotations with suggestions to move forward in implementing preemptive PGx for the individualization of treatment regimens for children with ALL.Keywords: pharmacogenetics, childhood ALL, implementation

Contemporary cooperative group lymphoma trials have developed smaller radiation (RT) fields based on interim (i) or end-of-systemic therapy (EST) PET scans. These fields are used as a "boost" following standard-of-care involved site RT (ISRT) or to replace ISRT entirely. These fields lack standardized nomenclature, complicating comparison of RT approaches across studies. The NRG hematologic working group convened a forum of radiation oncology lymphoma leaders from the National Clinical Trials Network (NCTN) groups (NRG Oncology, COG, SWOG, Alliance for Clinical Trials in Oncology (Alliance), ECOG-ACRIN, CCTG). The forum's objective was to establish standardized nomenclature for contemporary lymphoma RT target volumes. This nomenclature was developed through a comprehensive review of RT volumes utilized in 6 NCTN group lymphoma protocols after 2012 that included non-standard ISRT fields. A classification was developed based on the different fields described in the protocols and nomenclature was chosen to represent the fields. Analysis of the protocols (Table) revealed 5 non-mutually exclusive RT volumes, defined by our group as: ISRT, residual site radiotherapy (RSRT), and 3 PET-directed radiotherapy (PD-RT) types. ISRT considers post-chemo anatomic changes in the axial dimension only, and generally includes the full cranial-caudal extent of pre-chemo disease. RSRT targets only the post-chemo CT-anatomical mass, regardless of its PET avidity and irrespective of pre-chemo disease extent. ISRT and RSRT are independent of EST PET imaging. Conversely, PD-RT is only feasible with EST PET or iPET, and exclusively targets PET-positive disease. The 3 PD-RT types include: PET-directed involved site radiotherapy (pISRT), PET-directed residual site radiotherapy (pRSRT), and PET-directed residual PET radiotherapy (pRPRT). The pISRT target volume includes and follows the superior-inferior aspect of the pre-chemo involved disease site(s) that remain(s) PET-avid on post-treatment imaging. pRSRT target volume includes only the post-systemic therapy CT-anatomical residual mass that contains the PET-avid lesion on EST ± iPET imaging, without including sites that achieved complete metabolic response. pRPRT target volume includes only the PET-avid focus, irrespective of the corresponding adjacent non-PET-avid CT-anatomical disease surrounding it. Detailed target delineation and concept illustrations will be presented at the meeting. NRG Oncology, COG, SWOG, Alliance, ECOG-ACRIN, and CCTG propose a consensus nomenclature for contemporary RT target volumes to be used on lymphoma protocols. Recommendations for using these target volumes are beyond the scope of this work and require comparative studies and/or in-depth analysis of patterns of relapse. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) is an important modality in the management of lymphoma. However, there has been a significant decrease in the use of RT in clinical practice and research studies. This may be due to underrepresentation of radiation oncology (RO) in lymphoma leadership positions. The NRG Hematologic Malignancies Working Group (NRG heme) aimed to assess the inclusion of RO among other specialties in the various lymphoma academic leadership positions. We conducted a comprehensive review of the official websites of National Comprehensive Cancer Network (NCCN), lymphoma cooperative research groups (ECOG, SWOG, NCTN, NRG, EORTC, COG, GHSG, LYSA, CIBMTR), lymphoma research foundations (Leukemia & Lymphoma Society, AACR, EHA, LRF) and hematology journals (Blood, Lancet Heme, AJH, Blood Cancer J, Haematologica, HemaSphere, BJH, Blood Adv; date of access 12/7/2023). The evaluation of participation from various specialties, including RO, hematology/oncology (HO), pathology/molecular biology (PM), diagnostic radiology (DR), and other fields such as patient advocacy, public health, pharmacy, biostatistics, dermatology, and research coordinators, was assessed. Median percentages were then calculated and reported for each specialty. Detailed breakdown of committees and research groups by specialty is provided in the Table. Among the 8 NCCN lymphoma guidelines' committees, HO had a median involvement of 77%, while RO, PM and DR had 6%, 7.5% and 0%, respectively. Of the 9 identified lymphoma research cooperative groups, HO had a median involvement of 50%, compared to RO's 11%, PM's 5% and DR's 3%. Among the 4 lymphoma research foundations, HO had a median involvement of 80%, with 15% for PM and 0% for RO and DR. The editorial boards of the 8 highest impact hematology journals had a median involvement of 82% for HO, 14.5% for PM and 0% for RO and DR. HO holds a predominant role in the clinical and research domains of lymphoma, whereas the representation of RO and DR is notably limited. Acknowledging the indications and the significance of therapeutic and diagnostic RT in hematology/lymphoma research and multidisciplinary care, the NRG heme is actively dedicated to augmenting its representation for the benefit of patients. [ABSTRACT FROM AUTHOR]

Unirradiated relapsed/refractory (r/r) non-Hodgkin lymphoma (NHL) patients who undergo anti-CD19 Chimeric Antigen Receptor T-cell Therapy (CART) have a predominant localized pattern of relapse, the significance of which is heightened in individuals with limited/localized pre-CART disease. This study is the first to report on the role of bridging radiotherapy (BRT) for patients with limited (< 5 involved sites) disease prior to CART. Following Institutional Review Board approval, a retrospective review from 2018 to 2023 across 3 centers was performed and identified 150 patients with r/r B-cell NHL who received CART and had < 5 disease sites prior to leukapheresis. Ann Arbor staging was used to define the number of involved disease sites. Bridging treatment (radiation and/or systemic therapy) was defined as treatment administered between leukapheresis and CART infusion. Bridging radiation (BRT) was defined as comprehensive, treating all PET-avid disease sites, or focal. Local relapse was defined as disease recurring at the same site(s) (with or without new sites) on PET imaging prior to CART infusion. Relapse-free survival (RFS) was defined from CART infusion to any disease relapse/progression. Event-free survival (EFS) was defined from CART infusion to any disease relapse/progression, initiation of post-CART consolidative/salvage therapy, or death. Prior to CART infusion, 48 (32%) patients received BRT and 102 (68%) did not. The median number of involved disease sites prior to leukapheresis was 2 (range = 1-4). Female gender and extranodal involvement were more common in the BRT group. The median equivalent 2 Gy BRT dose was 25.5 (range = 9.3-43) Gy. There were no grade ≥ 3 BRT-related toxicities. The median follow-up was 21 months. Following CART infusion, BRT patients had better objective response rate (92% vs 78%, P = 0.046). Sustained complete response without subsequent relapse was higher with BRT (54% vs 33%, P = 0.016). Local relapse in sites present prior to CART was lower in the BRT group (21% vs. 46%, P = 0.003). BRT patients had improved 2-year RFS (53% vs 44%, P = 0.023) and 2-year EFS (37% vs 34%, P = 0.039) compared to no BRT patients. Further improvement in 2-year RFS (57% vs 44%, P = 0.003) and 2-year EFS (44% vs 32%, P = 0.008) was seen in patients who received comprehensive BRT to all active disease sites (n = 37) compared to those who did not (n = 113). The impact of BRT was most prominent in patients who had ≤ 2 pre-CART involved disease sites, with 2-year RFS of 62% in patients who received BRT compared to 42% in those who did not (P = 0.002). This improvement in RFS was not seen in patients who had > 2 pre-CART involved disease sites. BRT prior to CART for patients with limited (< 5 involved disease sites) r/r NHL improves response rate, local control, RFS, and EFS without causing significant toxicities. Larger prospective studies are needed to confirm our findings, and clinical predictors of which patients will benefit most from BRT are needed. [ABSTRACT FROM AUTHOR]

Gray zone lymphoma (GZL) is a relatively rare disease predominantly affecting young adults with purportedly poor outcomes with current treatment approaches. The role of radiation therapy (RT) in the management of GZL is not well established. This is the largest study to report on the outcomes of GZL patients treated with and without RT. A retrospective review of 30 patients with GZL treated across 3 institutions from 2009 to 2021 was performed. Event-free survival (EFS) was defined from initiation of frontline chemotherapy (CHT) to disease progression/relapse, initiation of salvage therapy, or death. Local control (LC) was defined from RT start date to in-field recurrence. The median age was 32 (range: 18-86) years, and 16 (53%) patients had early stage (I-II) disease. Bulky mediastinal disease was present in 63% of patients, and the median tumor diameter was 10 (range: 1.5-18) cm. Patients received ABVD (20%), RCHOP (33%), or REPOCH (47%) as frontline CHT. Among 25 patients with interim PET/CT scan, there were 6 rapid early responders and 14 slow early responders (SER), with 2-year EFS of 33% and 24%, respectively (p = 0.13). After the completion of CHT, 15 (50%) patients achieved complete response (CR) and 10 (33%) achieved partial response (PR), with 2-year EFS of 46% and 10%, respectively (p = 0.004). RT was given to 9 patients in CR (n = 3) or in PR (n = 6). The median RT dose was 36 (30.6-48.6) Gy, at 1.8-2 Gy/fraction. Those receiving RT had bulkier disease at diagnosis (p = 0.049) and lower rates of CR following CHT (p = 0.03). After RT, 3/6 (50%) PR patients converted to CR. At a median follow-up of 4 years, the 2-year EFS was 26% for all patients, 33% for RT and 23% for noRT (p = 0.44). Among patients who did not receive upfront RT and experienced progression (n = 17), 16 (94%) relapsed in pre-existing sites. The 5-year OS was 80% for all patients, 88% for RT and 78% for no RT (p = 0.63). Patients who achieved PR to CHT and received RT had better 2-year EFS (17% vs 0%, p = 0.007) compared to patients who did not receive RT. Similarly, patients with SER who received RT had superior 2-year EFS (33% vs 13%, p = 0.038). Patients with bulky mediastinal disease had a 2-year EFS of 43% with RT and 11% without RT (p = 0.08). After 1st line treatment, 22 (73%) patients relapsed and 18 were successfully salvaged with a sustained CR. The most common salvage regimen involved high dose CHT followed by hematopoietic cell transplantation (HCT) (n = 15). RT was given for 7 patients in the relapsed/refractory setting (consolidative peri-HCT n = 4; definitive salvage n = 3) and 5 (71%) achieved a sustained CR. Among the 16 patients who received RT in the upfront (n = 9) or salvage (n = 7) setting, 3 patients experienced in-field recurrence translating to 2-year LC of 79%. GZL patients have high risk of relapse and maximal upfront combined modality therapy should be considered. RT provides good local control and improves EFS particularly for SER, PR, and bulky mediastinal disease. [ABSTRACT FROM AUTHOR]

The role of postmastectomy radiation therapy (PMRT) following primary systemic therapy (PST) in HER-2 positive breast cancer (Her2+BC) remains poorly understood. The current study evaluates PMRT based on the pathological response to PST in Her2+BC. TRYPHAENA and NeoSphere are randomized phase II trials that investigated PST for Her2+BC. Our study is a pooled analysis of both trials, including 312 node-positive patients treated with HER-2 targeted PST followed by mastectomy with or without PMRT. The primary endpoint is loco-regional recurrence-free survival (LRRFS). Our analysis included 172 (55%) patients who achieved nodal pCR and 140 (45%) patients who did not. Patients with nodal pCR had a 5-year LRRFS of 97% with PMRT delivered in 98 patients (57%). Patients without nodal pCR had a 5-year LRRFS of 87% with PMRT delivered in 93 patients (66%). Patients with ypN1 (n = 62) disease who received PMRT (n = 40) had a 5-year LRRFS of 85% as compared to 89% in those who did not (n = 22); (p = 0.60). A significant LRRFS difference was noted in patients with ypN2-3 (n = 78) disease who received PMRT (n = 53) compared to those who did not (n = 25) (5-year LRRFS 92% vs. 75%; p = 0.019). On multivariate analysis, clinical nodal disease at diagnosis and nodal pCR were significantly associated with loco-regional recurrence (LRR). Her2+BC patients who achieve nodal pCR after PST have excellent loco-regional control which supports de-escalation of PMRT. [ABSTRACT FROM AUTHOR]

Up to30% of non-Hodgkin lymphoma (NHL) patients achieve a partial response (PR) to anti-CD19 Chimeric Antigen Receptor T-cell Therapy (CART) on day +30. Most PR patients relapse and only 30% achieve spontaneous complete response (CR) without additional therapies. This study is the first to report on the role of consolidative radiotherapy (cRT) for PR PET-avid disease on day +30 post-CART in NHL. Aretrospective review across 3 institutions from 2018 to 2022 identified 60 patients with B-cell NHL who received CART and achieved PR (Deauville 4-5) with <5 PET-avid disease sites on day +30. Progression-free survival (PFS) was defined from CART infusion to any disease progression. Overall survival (OS) was defined from CART infusion to death. Local relapse-free survival (LRFS), calculated based on the total number of PR sites, was defined from CART infusion to local relapse (LR) in the PR site identified on day +30. cRT was defined as comprehensive (compRT) – treated all PR PET-avid sites – or focal (focRT). Followingday +30 PET scan, 45 PR patients were observed and 15 received cRT. Only one patient received consolidative systemic therapy and belonged to the cRT group. Prior to CART, bridging RT was given to 13 patients (9 in observation group and 4 in cRT group). There were no significant differences in the pre-CART and day +30 baseline characteristics, including the median size and SUVmax of the PR sites, between the two groups. However, the median number of PR sites on day +30 was higher in the cRT group (2 [range 1-3] vs 1 [range 1-3], p = 0.003). The median equivalent 2 Gy dose was 39.1 (Interquartile range 36.8-41) Gy, and the most common cRT regimen was 37.5 Gy in 15 fractions. The median follow-up was 21 months. Among the observed patients, 15 (33%) achieved spontaneous CR, and 27 (60%) experienced disease progression with all relapses involving the initial PR sites. Among patients who received cRT, 10 (67%) achieved CR, and 3 (20%) had disease progression with no relapses in the radiated PR sites. None of the 10 cRT patients achieving CR relapsed or required subsequent therapies. The 2-year PFS was 80% and 37% (p = 0.012) and the 2-year OS was 78% and 43% (p = 0.12) in the cRT and observation groups, respectively. Patients consolidated with compRT (n = 12) had superior 2-year PFS (92% vs 37%, p = 0.003) and 2-year OS (86% vs 43%, p = 0.048) compared to observed or focRT patients (n = 48). There were no grade 3+ RT-related toxicities. A total of 90 PR sites were identified; 64 were observed and 26 received cRT. Fourteen (22%) observed PR sites achieved spontaneous sustained CR and 42 (66%) experienced LR. Twenty-four (92%) PR sites consolidated with cRT achieved sustained CR and none experienced LR. The 2-year LRFS was 100% in the cRT sites and 31% in the observed sites (p<0.001). NHL patients who achieve PR by PET to CART are at high risk of local progression. cRT for residual PET-avid disease on day +30 post-CART appears to alter the pattern of relapse and improve LRFS and PFS. [ABSTRACT FROM AUTHOR]

The optimal way to utilize radiotherapy (RT) in conjunction with CD19 chimeric antigen receptor T-cell therapy (CART) for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL) remains unclear. RT can be used as bridging treatment (BRT) prior to CART cell infusion, or as salvage intervention (SRT) following CART for patients with residual or progressive disease. While both scenarios feature grossly visible chemoresistant lymphoma at the time of RT, the response to RT may be impacted by the biological differences of these patients and the optimal RT dose, technique, and timing that has not yet been identified. This study investigates whether delaying RT after CART infusion as salvage therapy compromises the RT local control effect when compared to BRT. Following IRB approval, 83 patients with aggressive r/r B-cell NHL who received CART and RT, either as BRT between leukapheresis and CART infusion or as SRT after CART infusion, between 2018 and 2021 at a multi-site single institution were retrospectively reviewed. RT local control rate (LC) was calculated based on the total number of irradiated sites and was defined from RT start date to in-field recurrence. In-field recurrence was defined as disease relapse overlapping the radiation planning target volume. Time-to-event analysis was estimated by Kaplan-Meier plot. Thirty-five patients received BRT and 48 received SRT. At the time of RT, patients who received BRT had bulkier (median diameter 8.7cm vs 5.5cm; p=0.01) and more diffuse disease (59% vs 35% p=0.04), compared to SRT. The median equivalent 2 Gy dose (EQD2) was 23.3 Gy (range 4-41 Gy) for BRT, significantly lower than that of SRT, 34.5 Gy (range 4-52) (p=0.002). Bridged disease sites had better response to treatment (complete response BRT 59% vs SRT 19%, p<0.001), and salvaged sites were more refractory/resistant to treatment (progression of disease/no response 11% vs 3.5%, p<0.001). Among 124 total irradiated sites identified, 8/59 (13%) bridged sites and 21/65 (32%) salvaged sites experienced in-field recurrence translating to 1-year site-specific LC of 84% and 62%, respectively (p=0.009). BRT followed by CART was associated with improved LC compared to SRT in r/r B-cell NHL despite significantly lower RT doses and higher disease burden at the time of radiation. This augmented local control may reflect a sensitization/immunomodulatory effect induced by the synergy of BRT and CART. The compromised LC in the salvage setting may owe to the absence of this synergy and/or potential radioresistance acquired by the post CART relapsed disease. [ABSTRACT FROM AUTHOR]

Significant relapse rates following CD19 Chimeric Antigen Receptor T-Cell Therapy (CART) for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL) remain a challenge. This study aims to better define the role of salvage radiotherapy (SRT) after CART. We retrospectively reviewed 48 patients with r/r aggressive B-cell NHL who received SRT following CART from 2018 to 2021. SRT local control rate (LC) - calculated based on the total number of irradiated sites, freedom from subsequent progression (FFSP), freedom from subsequent event (FFSE) – accounting for subsequent progressions and salvage therapies, and overall survival (OS) were defined from SRT start date. In-field recurrence was defined as disease relapse occurring within the radiation planning target volume. SRT was defined as comprehensive (compSRT) – treated all sites of active disease – or focal (focSRT). Limited disease was defined as disease amenable to comprehensive RT, either as localized (encompassable in one RT field) or oligo-diffuse (≤4 sites). Kaplan-Meier plots and Cox regression modeling were used to estimate the desired output. Median age of the cohort at time of CART infusion was 58 (range 19-73) years, and median time from CART infusion to SRT was 103 (range: 23-842) days. The median equivalent 2 Gy dose (EQD2) was 37.4 Gy (range 4-52 Gy) for compSRT and 24.2 Gy (range 4.7-48.8) for focSRT. The most common regimens were 36 Gy in 12 fractions in compSRT and 20 Gy in 5 fractions in focSRT. A total of 65 sites treated in 37 patients had adequate imaging follow-up after SRT. Of the irradiated sites, 21 lesions (32%) in 16 patients experienced in-field recurrence, translating to 1-year LC of 62%. No in-field recurrence occurred beyond 210 days. On univariate analysis, tumor size, SUVmax, and LDH >2x upper limit (UL) at the time of SRT were significantly associated with increased risk of in-field recurrence. On the multivariate analysis, LDH >2x UL (OR 6.5, CI: 1.8-24.3; p=0.005) and SUVmax (OR 1.06, CI: 1.002-1.12; p=0.044) retained significant association with in-field recurrence. There were 37 patients with limited disease and 11 with extensive disease and the 1-year OS was 39% and 0% (p<0.001), respectively. Among those with limited disease, 26 received compSRT and 11 received focSRT. At a median follow-up period of 20 months, patients with limited disease who received compSRT had significantly higher 1-year FFSP (31% vs. 0%; p<0.001), 1-year FFSE (19% vs. 0%; p=0.01), and 1-year OS (51% vs. 12%; p=0.028) compared to focSRT. Post-CART compSRT for r/r B-cell NHL is a reasonable salvage intervention for patients with limited relapsed disease and is associated with better FFSP, FFSE and OS compared to focSRT. Patients who have elevated LDH >2 x UL and high SUVmax prior to SRT are likely at the highest risk of in-field recurrence and may benefit from escalation of therapy. [ABSTRACT FROM AUTHOR]

Approximately 30% of patients treated with 4 Gy delivered at 2 Gy/fraction (4Gy) will experience local progression at 18 months after treatment. In 2020, we introduced 8 Gy delivered at 4 Gy/fraction (8Gy) into routine clinical practice at our institution. We hypothesized that 8 Gy would result in less local recurrences (LR) and more complete responses (CR) compared to 4 Gy, and herein report early outcomes. This was an IRB-approved retrospective review of patients treated from 2013 to 2024 with 4 Gy or 8 Gy for low grade B-cell lymphomas including follicular (FL) and marginal zone lymphoma (MZL). The reverse Kaplan Meier method was utilized to calculate cumulative incidence of local recurrence (LR) and CR, with death and initiation of systemic therapy as competing risks. Univariate and multivariable Cox models were performed to identify any patient, disease, or treatment factors associated with LR and with CR. 77 sites of disease (68 patients) were treated with 4 Gy and 56 sites (49 patients) were treated with 8 Gy. The majority (71%) of 4 Gy was administered between 2013-2020, while 95% of 8 Gy was delivered from 2020-2023. Therefore, median follow up was 2.1, 5.8, and 1.2 years for the overall cohort, 4 Gy, and 8 Gy groups, respectively. The two treatment groups were balanced with respect to prior systemic therapy receipt, previous non-local radiation for lymphoma, and size of GTV (gross tumor volume, cm). FL represented a larger proportion of the 8 Gy group (64%) than the 4 Gy group (35%), which approached statistical significance (p=0.058). More patients with orbital tumors were treated with 4 Gy: 40% of the 4 Gy vs 4% of the 8 Gy group. There were 20 local recurrences in the 4 Gy group (26.0%) and four in the 8 Gy group (7.1%) (HR 2.63, 0.74 – 9.30, p=0.134). The 2, 3, and 5-year cumulative incidences of LR after 4 Gy were 19%, 25%, and 30%. The 2-year cumulative incidence of LR after 8 Gy was 14%. On univariate analysis, nodal sites of disease were more likely to recur (HR 3.63, 1.30 – 10.11, p=0.014): 2-year cumulative incidence of nodal LR was 32.6%. Larger tumors were also more likely to recur (HR 1.25 per 1 cm size, p=0.010). There was no difference in LC between 4 Gy and 8 Gy within the FL and MZL groups when examined individually (p=0.336 and p=0.251, respectively). The cumulative incidence of CR at one year after treatment was 58.5% for the 4 Gy group and 83.5% for the 8 Gy group. On univariate analysis, 4 Gy was associated with a lower chance of CR (HR 0.53, 0.32 – 0.89, p=0.016), which on multivariable analysis did not differ depending on size of GTV. For MZL, 4 Gy produced an inferior CR (HR 0.47, 0.23 – 0.95, p=0.037), while for FL there was no difference in CR between the two doses. Early outcomes of utilizing 8 Gy for indolent lymphomas compare favorably to 4 Gy, with better CR rates and encouraging local control rates. Longer follow-up and additional studies are needed, and toxicity data are forthcoming. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Anti-CD19-directed chimeric antigen receptor T-cell therapy (CART) is a new treatment option for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL). We reviewed the outcomes of patients receiving CART and the potential role of bridging radiation therapy (bRT) in reducing local recurrences.Materials/methods: Following IRB approval, we retrospectively reviewed 120 patients with NHL who received CART between 2018 and 2020 at a multi-site single institution. Baseline clinical and treatment characteristics were compared between patients who received bRT (≤30 days prior to CART or after leukapheresis) and those who did not using chi-square and Fisher's exact tests. Overall-survival (OS) and progression-free survival (PFS) were defined from date of CART infusion and estimated by Kaplan-Meier curves. Response rate was based on the post-CART PET scan with the best attained response.Results: Of 120 patients who received CART, 2 (1.7%) died soon after CART infusion from infection. Of the 118 remaining patients (88% diffuse large B-cell, 7.5% high-grade B-cell, 2.5% mantle cell, 2% primary mediastinal B-cell), 14 (12%) received bRT, while 104 (88%) did not (noRT). There were no significant differences in the baseline clinicopathological characteristics between the two groups. bRT was delivered with a median dose of 20 Gy (range 15-36) in 5 fractions (range: 3-24). No grade 2+ radiation-related toxicities were noted. Median time between end of bRT and the CART infusion was 19 days (range: 8-38). Rates of grade > 2 ICANS (21% vs 16%; P = .70) and CRS (7% vs 2%; P = .32) were not significantly different between bRT and noRT, respectively. Median follow-up was 7 months (range: 1-31). There were 42 (36%) deaths: 31 due to progression, 9 due to infection and 2 of unknown causes. The 6-month and 1-year OS were 67% and 67% for the bRT, and 76% and 63% for the noRT groups, respectively (P = .96). The median time to CART failure for the cohort was 78 days (range: 22-627). The 6-month and 1-year PFS were 47% and 47% for the bRT, and 47% and 42% for the noRT groups, respectively (P = .73). Median time to achieve the best response on PET scan was 30 days (range 22-382). Sixty patients (51%) achieved complete remission to CART, 7 (50%) in the bRT group and 53 (51%) in the noRT group, while 40 (34%) achieved partial remission, 5 (36%) in the bRT group and 35 (34%) in the noRT group (P = .97). For the entire cohort, pattern of failure analysis revealed that progression in pre-existing sites alone or in combination with new sites was the predominant site of failure in the bRT and noRT groups (86% and 88%, respectively). However, 71.4% of progressions in the bRT group occurred outside the RT field (n = 5), compared to 28.6% (n = 2) inside the RT field.Conclusion: Bridging RT prior to CAR T-cell infusion is well tolerated and appears to provide excellent in-field local control. Large prospective studies evaluating the value of integrating bRT with CAR T-cell therapy are needed. [ABSTRACT FROM AUTHOR]