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Background: Malignant epithelial neoplasms of the lacrimal apparatus are rare and are typically treated with surgery and occasionally adjuvant radiation therapy (RT). The purpose of this study was to assess treatment outcomes by type of surgery (orbital exenteration vs eye-sparing surgery) and clarify the role of adjuvant RT for this rare disease.Methods: Forty-six patients with malignant epithelial neoplasms of the lacrimal apparatus were treated at a single institution from 1945 through 2008. Twenty-seven patients (59%) were treated with orbital exenteration and 19 (41%) with eye-sparing surgery; 64% of the orbital exenteration group and 83% of the eye-sparing surgery group also received adjuvant RT (median dose, 60 grays). Median follow-up time for all patients was 38 months (range, 3-460 months).Results: For the orbital exenteration and eye-sparing surgery groups, the 5-year overall survival (OS) rates were 59% and 62%, and the 5-year disease-free survival (DFS) rates were 49% and 39%, respectively (P = .56, P = .35). Tumor status (T1-2 vs T3-4) was associated with OS (P = .02), and tumor size (<3.5 vs >3.5 cm) with DFS (P = .015). Median time to locoregional recurrence was 85 months for orbital exenteration, and 123 months for eye-sparing surgery. All patients who did not receive RT experienced local recurrence, and RT extended time to locoregional recurrence (median 460 vs 30 months, P = .009). Seven grade ≥3 complications were experienced after adjuvant RT.Conclusions: For appropriately selected patients, an eye-sparing surgery for lacrimal apparatus tumors can achieve similar survival outcomes to those in patients treated with an orbital exenteration. Adjuvant RT should be considered for all patients presenting with these rare tumors. [ABSTRACT FROM AUTHOR]

Purpose: Presence of MYC and BCL2 translocations (i.e. double-hit lymphoma, DHL) in large B-cell lymphoma (LBCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy., Methods/materials: Patients with LBCL that received their first course of RT for relapsed/refractory (r/r) disease between 2008-2020 were eligible if there was adequate pathologic evaluation to be categorized as DHL versus non-DHL as per WHO (5 th edition). Separate analyses were conducted by treatment intent. Predictors for response (complete and partial) and local recurrence (LR) were evaluated using Cox regression analysis. LR analysis was restricted to curative-intent patients to ensure adequate follow-up., Results: 383 patients (102 DHL, 281 non-DHL, 44% curative) were treated to 447 sites. Median time from diagnosis to RT was 11.6 months, with 38.7% patients having primary chemorefractory disease, 37.4% having received >2 lines of systemic therapy, and 24% status post stem cell transplant. Median biological equivalent dose (alpha/beta 10) was 28 Gy (range 3.2-60.0) for palliative and 46.9 Gy (range 6.4-84.0) for curative-intent patients. With a median follow-up of 41.1 and 41.5 months among curative and palliative patients, respectively, response was high (81.1% curative, 60.1% palliative). On univariate analysis, DHL pathology was not associated with RT response in either curative or palliative patients. Among curative patients, 2-year LR rate was 38.8%. On multivariable analysis, DHL pathology was associated with a 2 times higher risk of LR (95% CI 1.05-3.67,p=.03), with a crude LR rate of 42.9% (DHL) versus 28.9% (non-DHL). RT was well tolerated with low rates of grade 3 or higher acute toxicity (1.8% curative, 2.9% palliative)., Conclusions: Relapsed/refractory LBCL remains radioresponsive with 60-80% response rate to RT. While DHL pathology does not appear to influence RT response, its presence is associated with higher rates of local recurrence, suggesting it may be more radioresistant., Competing Interests: Declaration of competing interest Richard Hoppe: royalties from UpToDate, honoraria from Mayo Clinic, steering committee for ILROG, executive committee for global nLPHL One Working Group. Nima Nabavizadeh: consulting for Grail LLC and Freenome, honoraria from MJH Lifesciences. Chirayu Patel: research grant from Varian. Ima Paydar: full time employee for Merck. John Plastaras: annual payment from proton advisory committee for IBA. Yolanda Tseng: honoraria from University of Maryland, chair of PCG lymphoma committee, co-chair of PTCOG lymphoma subcommittee, (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Extranodal NK/T-cell lymphoma (ENKTCL) is rare in the Western Hemisphere and is commonly treated with combined modality therapy (CMT)., Methods and Materials: We retrospectively reviewed 35 patients treated with Ann Arbor stage I/II ENKTCL between 1994 and 2015 at a large academic cancer center in the United States., Results: With 11.6 years median follow-up, median overall survival and progression-free survival were 13.5 and 7.5 years, respectively. Eighteen (51%) patients experienced disease relapse, with 5 regional nodal relapses, of which 2 experienced combined regional and distant relapses. All 5 regional nodal relapses occurred exclusively among patients not treated with elective nodal irradiation (ENI). ENI was associated with improved progression-free survival (hazard ratio [HR], 0.21; 95% CI, 0.09-0.52; P = .018) without significant association with OS (HR, 0.33; 95% CI, 0.11-0.94; P = .11). There was a trend toward improved local control with radiation dose to the primary tumor ≥50 Gy (HR, 0.29; 95% CI, 0.08-1.08; P = .098)., Conclusions: In this Western Hemisphere cohort of early-stage ENKTCL patients treated with CMT, ENI may have a potential clinical benefit, particularly in patients who are treated with non-asparaginase-containing CMT, such as in patients treated with radiation alone, patients treated with less intensive chemotherapy concurrently, or patients who are unable to tolerate intensive chemotherapy., Competing Interests: Paolo Strati is a consultant/on the advisory board for Roche-Genentech, Genmab-AbbVie, Kite-Gilead, Sobi, ADC Therapeutics, and AstraZeneca Acerta and has research support from Kite-Gilead, Sobi, ADC Therapeutics, AstraZeneca Acerta, and ALX Oncology. Loretta J. Nastoupil has received honorariums from AbbVie, AstraZeneca, BMS, Genentech, Genmab, Gilead/Kite, Incyte, Ipsen, Janssen, Merck, Novartis, Regeneron, and Takeda and has received research support from BMS, Caribou Biosciences, Genentech, Genmab, Gilead/Kite, IGM Biosciences, Ipsen, Janssen, Merck, Novartis, and Takeda., (© 2024 The Author(s).)

Contemporary lymphoma radiation target volumes that rely on post-systemic therapy imaging do not have standardised nomenclature. A forum of radiation oncology lymphoma leaders from the National Clinical Trials Network groups (NRG Oncology, Children's Oncology Group, SWOG Cancer Research Network, Alliance for Clinical Trials in Oncology, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, and the Canadian Cancer Trials Group) was convened and established standardised nomenclature for these volumes in the autumn of 2024. Involved-site radiotherapy includes the full cranial-caudal extent of prechemotherapy disease and takes into account axial anatomical changes only. Residual site radiotherapy targets only the postchemotherapy CT-anatomical mass. PET-directed radiotherapy exclusively targets PET-positive disease and includes three types: PET-directed involved site radiotherapy using the superior-inferior aspect of prechemotherapy involved disease sites that remain PET-avid on post-treatment imaging; PET-directed residual site radiotherapy using only the postchemotherapy CT-anatomical residual mass that contains the PET-avid lesion on post-treatment imaging, without excluding sites that had complete metabolic response; and PET-directed residual PET radiotherapy using only the PET-avid focus, irrespective of the corresponding adjacent non-PET-avid CT-anatomical disease surrounding it., Competing Interests: Declaration of interests LKB declares (in the last 36 months) payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events as visiting professor at University of Pittsburgh and Columbia University; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for the American Board of Radiology as Oral Boards chair Hematology. SF declares (in the last 36 months) payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events as visiting professor at University of Kansas; participation on the Proton Collaborative Group Data Safety Monitoring Board; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, as chair of Task Group Number 427 Technical Guidelines for the Use of Proton Therapy in Clinical Trials, for the American Association of Physicists in Medicine. JCG reports (without time limit) research in this publication was supported by the National Cancer Institute of the US National Institutes of Health, under award number U10CA180821 (to the Alliance for Clinical Trials in Oncology). JCG declares (in the last 36 months) grants or contracts from Intra-op Medical as institutional support for clinical trial; honorarium payments from DAVA Oncology and Primo-Oncology; support for travel paid by Alliance for Clinical Trials in Oncology to attend their group meeting as the Publication Committee co-chair; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, as Publications Committee co-chair at Alliance for Clinical Trials in Oncology, president and immediate past president, and a member of the board of directors at the International Society of Intraoperative Radiation Therapy, president and past president; is a councillor at the Ohio Radiological Society, Small Cell Lung Cancer Guideline, and a committee member at National Comprehensive Cancer Network. CSH declares (in the last 36 months) leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, as chair of the Radiation Oncology Committee at SWOG since June, 2023. BSH declares (in the last 36 months) leadership or fiduciary role in other board, society, committee, or advocacy group, unpaid, as NRG Hematologic Working Group co-chair; and travel support to semi-annual meetings from the Children's Oncology Group. SAM declares (in the last 36 months) support for travel to Children's Oncology Group meetings paid for by the Children's Oncology Group, and travel to a National Comprehensive Cancer Network guidelines meeting paid for by the National Comprehensive Cancer Network; leadership or fiduciary role in other board, society, committee, or advocacy group, unpaid, as Children's Oncology Group Hodgkin Lymphoma Committee radiation oncology/imaging lead, American Radium Society Appropriate Use Criteria–Lymphoma chair, and a member of the International Journal of Radiation Oncology, Biology, Physics editorial board. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: Definitive intent radiation therapy (RT) for early-stage mucosa-associated lymphoid tissue (MALT) lymphoma typically includes a dose of 24 to 30 Gy. While modest, these doses may have associated toxicity. For patients with indolent B-cell lymphoma, there is increasing support for the use of ultra-low-dose RT (ULDRT) using 4 Gy in 2 fractions as part of a response-adapted approach, as high rates of complete response have been documented. This paradigm has been prospectively evaluated in the management of orbital and gastric indolent B-cell lymphomas; however, there is limited data guiding the use of ULDRT for lung MALT., Methods: We conducted a retrospective review of 20 patients at our institution with lung MALT treated with ULDRT as part of a response-adapted approach. Clinical variables including prior systemic therapy and symptoms were abstracted from the electronic health record. Responses were assessed using the revised Lugano criteria., Results: At a median follow up of 17 months following 4 Gy (IQR, 8-37 months), we observed 100% local control. Nineteen patients (95%) experienced a complete response. No patients with stage IE disease at RT (17/20; 85%) experienced distant progression. Nine patients (45%) were symptomatic prior to RT, with improvement or resolution of symptoms in 7 (7/9; 78%). One patient developed grade 2 pleuritic pain following RT, which resolved with a brief course of steroids. No other toxicities were noted., Conclusions: ULDRT, given in a response-adapted approach, is effective and well tolerated by patients with lung MALT., Competing Interests: Bouthaina S. Dabaja reports research support from Seattle Genetics. Dai Chihara reports grants from BMS, Genmab, Morphosys, Ono, and Ipsen. He reports honoraria from Ono and BeiGene. Loretta J. Nastoupil reports grants from BMS, Caribou Biosciences, Epizyme, Genentech, Inc, Gilead/Kite, IGM Bioscience, Janssen, Novartis, and Takeda. She reports consulting fees from Sirpant and Interius BioTherapeutics and honoraria from ADC therapeutics, Atara, BMS, Caribou Biosciences, Epizyme, Genentech Gilead/Kite, Janssen, Novartis, and Takeda, and payment for expert testimony from Genentech, Inc/F. Hoffman-La Roche Ltd. Paolo Strati reports grants from AstraZeneca-Acerta, ADC Therapeutics, and ALX Oncology, and consulting fees from Roche-Genentech, Kite Gilead, Hutchinson Medipharma, AstraZeneca-Acerta, Sobi and TB Therapeutics, and ADC Therapeutics. Susan Y. Wu reports grants from Kite/Gilead, and consulting feeds RadOnc Questions. Sattva S. Neelapu reports grants from Kite/Gilead, BMS, Allogene, Precision Biosciences, Adicet Bio, Sana Biotechnology, and Cargo Therapeutics. He reports consulting fees from Kite/Gilead, Merck, Sellas Life Sciences, Athenex, Allogene, Incyte, Adicet Bio, BMS, Bluebird Bio, Fosun Kite, Sana Biotechnology, Caribou, Astellas Pharma, Morphosys, Janssen, Chimagen, ImmunoACT, Orna Therapeutics, Takeda, Synthekine, Carsgen, Appia Bio, and GlaxoSmithKline. He reports stock from Longbow Immunotherapeutics and intellectual property related to cell therapy. Preetesh Jain reports grants from Seagen, BMS, Rafale Pharmaceuticals, and GSK. Raphael Steiner reports grants from Seagen, BMS, Rafale Pharmaceuticals, and GSK., (© 2024 The Authors.)

Introduction: The impact of bridging radiation therapy (bRT) for CAR T-cell therapy on absolute lymphocyte count (ALC) kinetics and treatment outcome is unknown., Methods: We retrospectively reviewed adults with relapsed/refractory aggressive large B-cell lymphoma (LBCL) who received bRT prior to CD-19 CAR-T between 11/2017-4/2023. 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. PFS, DSS, and OS were modeled via Kaplan-Meier., Results: Fifty-one patients received bRT, of which 13 (25.5%) had bulky disease (≥7.5cm). The median bRT dose was 30Gy (range: 4-48Gy); 26 patients (51%) received ≥30Gy. 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 (CC) timepoint. There was no correlation between post-RT Grade ≥3 lymphopenia and the receipt of comprehensive bRT, combined modality bridging, ≥30Gy bRT, or bRT to ≥15% of BM (all p>0.2). Among patients with Grade 0-2 lymphopenia pre-RT, increased conversion to Grade ≥3 lymphopenia post-RT correlated with comprehensive or ≥30Gy bRT, but these factors did not impair ALC recovery at CC. There was no association between ALC Δ RT or post-RT ALC with 30 or 90 day response (p>0.25), DSS, PFS, or OS (p>0.3)., Conclusions: Lymphocyte change during bRT is not associated with CAR-T outcomes. Persistent cytopenia risk following bRT is not associated with bRT to ≥30Gy, ≥15% of BM, or comprehensive coverage. While bRT can be delivered safely, we urge careful treatment planning when incorporating into pre-CAR-T regimens., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: There currently are no established formal mentorship and training programs for radiation oncology (RO) trainees to learn trial design, creation, writing, or implementation. There only exists informal training on analyzing clinical trials in RO residency programs. The integration of a longitudinal formal training and mentorship program for clinical trialists-consisting of clinical trial education, design, mentorship, and implementation during the RO residency education-will give residents not only formal teaching in the subject but also strong tools and requisite mentorship in hopes to help them succeed as future academic physicians and leaders in the field of RO., Methods and Materials: We developed a clinical trial training pathway in 2018 at MD Anderson Cancer Center, proposing it as a pilot program. The "Fletcher-Cox Pathway" was accepted with a highly positive response by trainees and is now offered as a standard option to RO trainees at our institution., Results: With the guidance of their principal investigator, residents participating in this pathway design and submit a clinical trial for institutional review board review. In 2019, after implementation of the pilot program, 4 of the incoming 7 residents joined the pathway. The program continues, and the current cohort of trainees have received training in clinical trial design and worked with dedicated mentor(s) regarding clinical trial ideas; their studies are currently accruing patients., Conclusions: This pilot program has been viewed by trainees and mentors as successful; it highlights how a structured approach meets a clear need within RO training. We envision the creation of a national platform to increase access, whereby programs adopt this clinical trialist educational pathway, which ultimately leads to the development of a robust clinical trial community with communal resources. We hope that this not only improves and provides educational initiatives to all trainees but also initiates further collaboration., Competing Interests: None., (© 2024 The Authors.)

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.)

Importance: Radiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common., Objective: To determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity., Design, Setting, and Participants: This single-institution, phase 2 prospective nonrandomized controlled trial of a response-adapted strategy involved 50 evaluable patients with stage I to IV indolent B-cell lymphoma of the ocular adnexa enrolled between July 2015 and January 2021. This treatment approach was also retrospectively evaluated with a separate 55-patient cohort treated between March 2013 and October 2021. All data were analyzed between November 2021 and December 2023., Interventions: Patients were treated with ultralow-dose radiation therapy to 4 Gy in 2 fractions and assessed for response at 3-month intervals. Patients with persistent orbital lymphoma were offered an additional 20 Gy in 10 fractions to complete the response-adapted treatment., Main Outcome and Measures: The primary end point was 2-year local orbital control within the irradiated field after response-adapted therapy. Secondary end points included overall survival and complete response rate., Results: The 50 prospective patients were a median (range) of 63 (29-88) years old, and 31 (62%) were female. Among the 50 patients, 32 (64%) had mucosa-associated lymphoid tissue lymphoma, 12 (24%) had follicular lymphoma, and 6 (12%) had unclassifiable low-grade B-cell lymphoma. Thirty-one patients (62%) had stage I disease, and 36 (72%) were newly diagnosed. At a median follow-up of 37.4 (95% CI, 33.7-52.5) months, the 2-year local control rate was 89.4% (95% CI, 81.0%-98.7%), and the 2-year overall survival rate was 98.0% (95% CI, 94.1%-100%); 45 patients (90.0%; 95% CI, 78.2%-96.7%) experienced a complete response to response-adapted radiation, including 44 patients with a complete response to ultralow-dose radiation and 1 patient with a complete response after an additional 20 Gy. No local recurrences were observed among patients with a complete response to response-adapted therapy. No grade 3 or higher toxic effects were observed. In a planned subset analysis of 22 patients with newly diagnosed, untreated stage I mucosa-associated lymphoid tissue lymphoma, the 2-year local control rate was 90.7% (95% CI, 79.2%-100%), and the 2-year freedom from distant relapse rate was 95.2% (95% CI, 86.6%-100%)., Conclusion and Relevance: In this nonrandomized controlled trial, response-adapted ultralow-dose therapy for indolent orbital B-cell lymphoma resulted in reduced radiation exposure, negligible toxic effects, and excellent disease outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT02494700.

For localized breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), surgical resection is crucial; however, radiation therapy (RT) can be utilized as local-regional therapy if surgery is incomplete or not recommended. We present the case of a woman with BIA-ALCL who received systemic therapy and consolidation RT., Competing Interests: Dr. Pinnix has research support from Merck. Otherwise, none of the authors report any relevant conflict of interest. Dr. Hunt has the following disclosures: Medical Advisory Board – ArmadaHealth and AstraZeneca; Research funding to my institution – Cairn Surgical, Eli Lilly & Co., Lumicell., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy., Objective: Our aim was to characterize treatment options for PCSM-LPD, with a focus on the role of radiotherapy., Methods: This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM-LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy., Results: All patients achieved a complete response (CR). Sixteen patients (35%) received focal radiotherapy, with a CR in 15 (94%). The CR rate following ultra-low-dose radiotherapy (4 Gy in 1-2 fractions) was 92%. There was no grade 3 toxicity after radiotherapy. Thirty patients were managed without radiotherapy, with excision and observation or steroids., Conclusion: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder has excellent outcomes, and management strategies may include observation following biopsy, steroids, or radiation. Ultra-low-dose radiotherapy results in excellent outcomes with limited toxicity and is effective for persistent lesions after steroidal therapy., (© 2024 the International Society of Dermatology.)

Competing Interests: We declare no competing interests.

Background: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach., Methods: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment., Findings: Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths., Interpretation: Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity., Funding: National Cancer Institute., Competing Interests: Declarations of interests CCP has received research support from Merck. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: Radiation therapy (RT) is the standard treatment for solitary plasmacytoma (SP); however, the optimal management of RT-refractory SPs is unknown. We examined outcomes after early systemic therapy, surgical resection, or observation for patients with RT-refractory disease and assessed the potential impact of treatment selection on disease outcomes., Methods and Materials: We retrospectively reviewed patients with SP treated with definitive radiation and evaluated at a single institution with persistent disease on imaging or biopsy. Descriptive statistics were used to characterize patient and disease characteristics and treatment outcomes., Results: Of 102 total SP patients, 17 (17%) were RT-refractory. The median RT dose was 45 Gy, and median follow-up was 71 months from end of RT. Fifteen patients had additional treatment for refractory disease at a median time of 9.5 months after RT, with the following subsequent interventions: surgical resection (n = 4), additional RT (n = 2), systemic therapy without evidence of multiple myeloma (MM; n = 4), systemic therapy for progression to MM (n = 5), and observation (n = 2). Of 4 patients treated with surgical resection, 3 progressed to MM 22 to 43 months after diagnosis. Of 2 patients treated with additional RT, neither responded, and both had pathologic confirmation of residual disease after the second course. Four patients treated with systemic therapy without MM all had complete responses on positron emission tomography and no subsequent MM progression. Eight patients were initially observed after RT for ≥12 months (n = 8) or ≥24 months (n = 6). Of the 2 patients in continued observation, both had stable/unchanged avidity after radiation treatment for 12 and 22 months and ultimately had a slow decrease of disease avidity over multiple years., Conclusions: Patients with RT-refractory SPs can achieve good local control with alternative therapies, such as surgery or systemic therapy, if needed. Additional RT does not seem to be effective. Given the known high rates of progression from SP to MM, close observation of asymptomatic persistent disease until disease progression is likely sufficient in most cases., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD IV on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median patient age was 37 years, and a high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received 6 cycles of AVD; 55% of patients did not receive the intended cumulative dose of BV (CDB); 28% of patients received two-thirds or less than the planned CDB. At a median follow-up time of 27.4 months (95% confidence interval [CI], 24.8-29), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% CI, 85.9-95.0). The impact of CDB on PFS was not significant (P = .15), nor was high CDB significantly associated with increased adverse events. In real-world experience, A + AVD is a highly effective treatment for patients with advanced-stage cHL, including for patients with prominent dose reductions of BV., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Over the past decade, concerns have arisen in radiation oncology regarding potential workforce supply and demand imbalance. The American Society for Radiation Oncology commissioned an independent analysis in 2022, looking at supply and demand in the United States radiation oncology workforce and projecting future trends for 2025 and 2030. The final report, titled Projected Supply and Demand for Radiation Oncologists in the U.S. in 2025 and 2030, is now available. The analysis included evaluating radiation oncologist (RO) supply (new graduates, exits from the specialty), potential changes in demand (growth of Medicare beneficiaries, hypofractionation, loss of indications, new indications) as well as RO productivity (growth of work relative value units [wRVUs] produced), and demand per beneficiary. The results demonstrated a relative balance between radiation oncology supply and demand for radiation services; the growth in ROs was balanced by the rapid growth of Medicare beneficiaries over the same period. The primary factors driving the model were found to be growth of Medicare beneficiaries and change in wRVU productivity, with hypofractionation and loss of indication having only a moderate effect; although the most likely scenario was a balance of workforce supply and demand, scenarios did demonstrate the possibility of over- and undersupply. Oversupply may become a concern if RO wRVU productivity reaches the highest region; beyond 2030, this is also possible if growth in RO supply does not parallel Medicare beneficiary growth, which is projected to decline and will require corresponding supply adjustment. Limitations of the analysis included uncertainty regarding the true number of ROs, the lack of inclusion of most technical reimbursement and its effect as well as failing to account for stereotactic body radiation therapy. A modeling tool is available to allow individuals to evaluate different scenarios. Moving forward, continued study will be needed to evaluate trends (particularly wRVU productivity and Medicare beneficiary growth) to allow for continued assessment of workforce supply and demand in radiation oncology., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Purpose: Radiation therapy (RT) and the antibody-drug conjugate brentuximab vedotin (BV) are standard-of-care treatment options for patients with certain B and T-cell lymphomas; however, there are limited data exploring the safety of concurrent BV and RT (BVRT)., Methods and Materials: We performed a single institutional retrospective review of 44 patients who received BVRT., Results: Twenty percent of patients (9/44) developed new grade 2 or higher (G2+) hematologic toxicity (HT) after BVRT, which was associated with radiation dose (median dose of 35 Gy in those with new G2+ HT compared with 15 Gy in those without; P < .001). Acute G2+ elevation in aspartate transaminase or alanine transaminase level was associated with administration of concurrent chemotherapy with BVRT (57% vs 21%; P  = .047) but was not associated with any RT factors. Local control (LC) was achieved in 24 of 42 patients (57%) with available follow-up. Ten patients (23%) proceeded to stem cell transplant or cellular therapy after BVRT at a median of 48 days (interquartile range, 27-188 days). At last follow-up, 10 patients (23%) remained without evidence of disease., Conclusions: Our analysis demonstrates that the combination of BV and RT is well tolerated, though care should be taken during RT planning to reduce the risk of HT. This combination can be considered for patients in need of both local and systemic disease control., (© 2023 The Author(s).)

Disproportionate sex, racial, and ethnic diversity remains in the radiation oncology physician workforce despite widespread awareness and longitudinal efforts to improve representation. In this collaborative review, we define the rationale and components of holistic review and how it can be best used to provide a comprehensive evaluation of applicants to residency programs in radiation oncology. We initially discuss the current state of diversity in the field of radiation oncology and highlight the components of the residency selection process that may serve to perpetuate existing biases. Subsequently, the Accreditation Council for Graduate Medical Education and Association of American Medical Colleges holistic review framework is reviewed in detail to demonstrate the balanced assessment of potential applicants. The implementation of holistic review in medical school and residency selection to date is examined to underscore the potential value of holistic review in the radiation oncology residency selection process. Finally, recommendations for the practical implementation of holistic review in radiation oncology trainee selection are outlined., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Despite remarkable progress in survival with the availability of novel agents, an overwhelming majority of patients with multiple myeloma (MM) have disease that relapses. Allogeneic (allo-) hematopoietic cell transplantation (HCT) is a potentially curative option for a subgroup of patients with high-risk MM. This study assessed the long-term outcome of MM patients who underwent allo-HCT while in first remission as consolidation treatment. Thirty-three patients with newly diagnosed MM who underwent allo-HCT as part of consolidation therapy between 1994 and 2016 were reviewed retrospectively. Of these patients, 70% underwent autologous HCT before allo-HCT. All patients were chemosensitive and achieved at least partial response before proceeding to allo-HCT. Most received nonmyeloablative/reduced-intensity conditioning (88%) and a matched sibling donor graft (85%). Acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 30% and 61% of patients, respectively. The median duration of follow-up was 64.1 months (range, 1.4 to 199.2 months) for all patients and 164.4 months (range, 56.0 to 199.2 months) for survivors. The median progression-free survival (PFS) was 36 months (95% confidence interval (CI), 8.6 to 73.0 months). The median time from treatment to progression was 73.0 months (95% CI, 30.6 months to not reached). The median overall survival (OS) was 131.9 months (95% CI, 38.4 months to not reached). Of all patients, 39% were alive for more than 10 years, with 46% (n = 6) without progression or relapse. The cumulative incidence of relapse was 18% at 1 year, 39% at 5 years, and 46% at 10 years post-allo-HCT. The cumulative incidence of nonrelapse mortality was 3% at 100 days, 18% at 1 year, 21% at 3 years, and 24% at 5 year post-allo-HCT. On multivariable analysis, high-risk cytogenetics were associated with a shorter PFS (hazard ratio [HR], 2.7; 95% CI, 1.01 to 7.21; P = .047) and OS (HR, 4.91; 95% CI, 1.48 to 16.27; P = .009). Achieving complete remission after allo-HCT also was associated with longer PFS (HR, 0.24; 95% CI, 0.09 to 0.64; P = .004) and OS (HR, .23; 95% CI, .07 to .72; P = .012). Allo-HCT may confer a survival advantage in a selected population of MM patients when performed early in the disease course; additional data on identifying the patients who will benefit the most are needed., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The role of radiation therapy (RT) varies across hematologic malignancies (HM). Radiation oncology (RO) resident comfort with specific aspects of HM patient management is unknown. The International Lymphoma RO Group (ILROG) assessed resident HM training opportunities and interest in an HM away elective. RO residents (PGY2-5) in the Association of Residents in RO (ARRO) database (n = 572) were emailed an anonymous, web-based survey in January 2019 including binary, Likert-type scale (1 = not at all, 5 = extremely, reported as median [interquartile range]), and multiple-choice questions. Of 134 resident respondents (23%), 86 (64%) were PGY4/5 residents and 36 (27%) were in larger programs (≥ 13 residents). Residents reported having specialized HM faculty (112, 84%) and a dedicated HM rotation (95, 71%). Residents reported "moderate" preparedness to advocate for RT in multidisciplinary conferences (3 [2-3]); make HM-related clinical decisions (3 [2-4]); and critique treatment planning (3 [2-4]). They reported feeling "moderately" to "quite" prepared to contour HM cases (3.5 [3-4]) and "quite" prepared to utilize the PET-CT five-point scale (4 [3-5]). Overall, residents reported feeling "moderately" prepared to treat HM patients (3 [2-3]); 24 residents (23%) felt "quite" or "extremely" prepared. Sixty-six residents (49%) were potentially interested in an HM away elective, commonly to increase comfort with treating HM patients (65%). Therefore, HM training is an important component of RO residency, yet a minority of surveyed trainees felt quite or extremely well prepared to treat HM patients. Programs should explore alternative and additional educational opportunities to increase resident comfort with treating HM patients., (© 2021. American Association for Cancer Education.)

Subspecialty exposure during medical school can be limited. Moreover, the COVID19 pandemic prevented most onsite elective medical student (MS) rotations during 2020. Therefore, we sought to create and assess the efficacy of an informal virtual elective (IVE) for MSs to explore radiation oncology (RO) at our institution. We created IVE activities including invitations to resident didactics, a faculty lecture series, and interactive virtual events with residents and faculty. MSs were offered RO resident and faculty mentors and the opportunity to deliver a lecture. Pre- and post-IVE evaluation surveys were sent to 27 4th year MSs. Surveys utilized importance ordering (1=most important; reported as median (interquartile range), free response, and Likert-type questions (5 = extremely, 1=not at all). Our IVE, held from July to October 2020, had a median of 11 students (range 7-18) attend each activity. Pre- and post-IVE surveys were completed by 22/27 (81%) and 20/27 (74%) MSs, respectively. In pre-IVE, MSs reported participating in the IVE for faculty/resident interaction (1.5 [1, 2]), networking (3 [2, 3]), and learning (4 [3-5]). In post-IVE, MSs reported benefit from faculty mentors (5 [4, 5]), delivering a presentation (5 [3-5]), and faculty lectures (4.5 [4, 5]). In post-IVE, MSs preferred a full onsite away elective (16, 80%) over an official virtual elective (1, 5%) or IVE (3, 15%). Overall, MSs reported that the IVE provided an adequate introduction to RO at our institution (4 [4, 5]). Alternative virtual elective experiences allow MSs to informally evaluate medical subspecialties and could be offered even if formal elective opportunities are available., (© 2021. The Author(s) under exclusive licence to American Association for Cancer Education.)

Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplantation (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. In this study, we retrospectively examined the possible effect of RT on PBPC collection. We reviewed the charts of 732 patients with MM treated with RT at our institution from 1999 to 2017, including patients who received RT prior to PBPC collection for planned ASCT. RT plans (both MM and non-MM RT) were reviewed to estimate the percentage of bone marrow (BM) treated using published estimates of skeletal BM distribution. Statistics were performed using Pearson correlation and the t-test. The 732 MM patients included 485 planned for ASCT; of these, 223 received RT prior to PBPC collection and were included in the final cohort. The median age at PBPC collection was 59 years (range, 33 to 80 years). For SIT, patients received combination regimens including the following agents: bortezomib (142 patients; 64%), lenalidomide (111 patients; 50%), and alkylators (46 patients; 21%). Nine patients (4%) received dexamethasone alone. The median cumulative %BM treated per patient was 6.7 (range .0 to 47.4). The median RT dose was 24 Gy (range, 10.0 to 75.6 Gy). Mobilization was performed using granulocyte-colony stimulating factor (G-CSF) alone (189 patients; 85%), G-CSF with plerixafor (15 patients; 7%), or chemotherapy (19 patients; 9%). A median of 7.8 × 10 6 CD34 + /kg PBPCs (range, .5 to 54.8× 10 6 CD34 + /kg) were collected in a median of 3 (range, 1 to 9) apheresis procedures. One hundred ninety-six patients (99%) collected ≥2.0 × 10 6 CD34 + /kg PBPCs, and 166 (83%) collected >5.0 × 10 6 CD34 + /kg PBPCs. The number of PBPCs collected was not associated with %BM treated (P = .15) or RT dose (P = .56). The number of apheresis procedures performed was not associated with %BM treated (P = .54) or RT dose (P = .85). The amount of PBPCs collected did not differ significantly between patients receiving RT to the pelvis/sacrum (P = .20) and those receiving RT to the spine (P = .13). The time to platelet engraftment was longer for patients with higher %BM treated (P = .02). Eleven patients did not undergo a confirmed ASCT, owing to patient preference (3 patients), trial therapy (1 patient), comorbidities (1 patient), election for hospice (1 patient), inadequate collection (4 patients), or inadequate follow-up (1 patient). In our study cohort, RT prior to ASCT did not impair successful ASCT. RT must be carefully planned and delivered to ensure safe incorporation into pre-ASCT treatment regimens., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A 18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, maximum standardised uptake value (SUV max ), total metabolic tumour volume (TMTV), and total lesion glycolysis (TLG) were calculated from the post-salvage/pre-ASCT PET scan. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 40% and 54% respectively. A D-5PS score of 5 (p = 0.0082, hazard ratio [HR] 2.09), high SUV max (p = 0.0015, HR 2.48), TMTV (p = 0.035, HR 1.83) and TLG (p = 0.0036, HR 2.27) were associated with inferior PFS. A D-5PS score of 5 (p = 0.030, HR 1.98) and high SUV max (p = 0.0025, HR 2.55) were associated with inferior OS. PET-derived parameters may help prognosticate outcomes after ASCT in patients with rrLBCL with residual disease after salvage chemotherapy., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

We aimed to investigate whether implicit linguistic biases exist in letters of recommendation (LORs) for applicants to radiation oncology (RO) residency. LORs (n = 487) written for applicants (n = 125) invited to interview at a single RO residency program from the 2015 to 2019 application cycles were included for analysis. Linguistic Inquiry and Word Count (LIWC) software was used to evaluate LORs for length and a dictionary of predetermined themes. Language was evaluated for gender bias using a publicly available gender bias calculator. Non-parametric tests were used to compare linguistic domain scores. The median number of the LORs per applicant was 4 (range 3-5). No significant differences by applicant gender were detected in LIWC score domains or gender bias calculator (P > 0.05). However, LORs for applicants from racial/ethnic backgrounds underrepresented in medicine were less likely to include standout descriptors (P = 0.008). Male writers were less likely to describe applicant characteristics related to patient care (P < 0.0001) and agentic personality (P = 0.006). LORs written by RO were shorter (P < 0.0001) and included fewer standout descriptors (P = 0.014) but were also more likely to include statements regarding applicant desirability (P = 0.045) and research (P = 0.008). While language was globally male-biased, assistant professors were less likely than associate professors (P = 0.0064) and full professors (P = 0.023) to use male-biased language. Significant linguistic differences were observed in RO residency LORs, suggesting that implicit biases related to both applicants and letter writers may exist. Recognition, and ideally eradication, of such biases are crucial for fair and equitable evaluation of a diverse applicant pool of RO residency candidates., (© 2020. American Association for Cancer Education.)

Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel. Patients with CV comorbidities, organ dysfunction, or lower performance status were often excluded in the clinical trials leading to their Food and Drug Adminsitration approval. An improved understanding of CV toxicities in the real-world setting will better inform therapy selection and management of patients receiving these cellular therapies. Here, we retrospectively reviewed the characteristics and outcomes of adult patients with relapsed/refractory large B-cell lymphoma treated with SOC axi-cel or tisa-cel. Among the 165 patients evaluated, 27 (16%) developed at least one 30-day (30-d) major adverse CV event (MACE). Cumulatively, these patients experienced 21 arrhythmias, four exacerbations of heart failure/cardiomyopathy, four cerebrovascular accidents, three myocardial infarctions, and one patient died due to myocardial infaction. Factors significantly associated with an increased risk of 30-d MACE included age ≥60 years, an earlier start of cytokine release syndrome (CRS), CRS ≥ grade 3, long duration of CRS, and use of tocilizumab. After a median follow-up time of 16.2 months (range, 14.3-19.1), the occurrence of 30-d MACE was not significantly associated with progression-free survival or with overall survival. Our results suggest that the occurrence of 30-d MACE is more frequent among patients who are elderly, with early, severe, and prolonged CRS. However, with limited follow-up, larger prospective studies are needed, and multidisciplinary management of these patients is recommended.

Objective: We sought to evaluate patients at a single academic institution in a prospective manner to report patient presentation, clinical course, treatment, and outcomes in breast implant ALCL patients., Background: Breast implant-associated anaplastic large cell lymphoma (breast implant ALCL) is an uncommon T cell lymphoma, which is associated with textured surface breast implants. The disease has received increasing attention over the last 20 years. Previous retrospective studies have begun to outline the clinical course of breast implant ALCL., Methods: We prospectively followed women with cytologically proven breast implant ALCL from 2014 to 2019. Demographic, clinical, treatment, and outcome data were collected and descriptive statistics were performed on variables of interest., Results: We identified 52 women with pathologically confirmed breast implant ALCL. Implants were placed for augmentation in 61.5% of women and reconstruction in 36.5% of women. All of the 41 patients with known implant information had implants with textured surface. The majority of patients presented with delayed seroma (69.2%) and without systemic symptoms (86.5%). Most patients with staging information presented with Stage IA disease. Patient outcomes were excellent with 2 disease recurrence (3.8%) and all patients ultimately achieved complete remission., Conclusions: Further evaluation of the prospective and growing database of patients with breast implant ALCL will further improve our understanding of the disease and its clinical course. Robust participation in the breast implant ALCL PROFILE registry will improve our knowledge of long-term outcomes after implant placement. Finally, increasing awareness for patients and providers will lead to earlier diagnosis and improved outcomes for patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, accounting for 30-40% of all non-Hodgkin lymphoma cases and presenting later in life, most often in the sixth decade. Although DLBCL is curable, long-term remission rates are only 60-80%. The most recent major advance in upfront therapy for DLBCL was the monoclonal anti-CD20 antibody rituximab, which was approved in the late 1990s; now, 25 years later, up to 40% of patients will experience primary refractory or relapsed disease, thereby underscoring the importance of salvage therapy. Radiation therapy can be highly effective in DLBCL, both initially as consolidation therapy and later as salvage therapy and is currently being explored in the context of immune and cellular therapies. The aim of this review is to examine the therapeutic approaches for relapsed or refractory DLBCL, with a focus on whether using radiation therapy as salvage therapy can improve the likelihood of cure.

Background and Purpose: We previously evaluated late cardiac disease in long-term survivors in the Childhood Cancer Survivor Study (CCSS) based on heart radiation therapy (RT) doses estimated from an age-scaled phantom with a simple atlas-based heart model (H Atlas ). We enhanced our phantom with a high-resolution CT-based anatomically realistic and validated age-scalable cardiac model (H Hybrid ). We aimed to evaluate how this update would impact our prior estimates of RT-related late cardiac disease risk in the CCSS cohort., Methods: We evaluated 24,214 survivors from the CCSS diagnosed from 1970 to 1999. RT fields were reconstructed on an age-scaled phantom with H Hybrid and mean heart dose (D m ), percent volume receiving ≥ 20 Gy (V 20 ) and ≥ 5 Gy with V 20  = 0 ( [Formula: see text] ) were calculated. We reevaluated cumulative incidences and adjusted relative rates of grade 3-5 Common Terminology Criteria for Adverse Events outcomes for any cardiac disease, coronary artery disease (CAD), and heart failure (HF) in association with D m , V 20 , and [Formula: see text] (as categorical variables). Dose-response relationships were evaluated using piecewise-exponential models, adjusting for attained age, sex, cancer diagnosis age, race/ethnicity, time-dependent smoking history, diagnosis year, and chemotherapy exposure and doses. For relative rates, D m was also considered as a continuous variable., Results: Consistent with previous findings with H Atlas , reevaluation using H Hybrid dosimetry found that, D m  ≥ 10 Gy, V 20  ≥ 0.1%, and [Formula: see text]  ≥ 50% were all associated with increased cumulative incidences and relative rates for any cardiac disease, CAD, and HF. While updated risk estimates were consistent with previous estimates overall without statistically significant changes, there were some important and significant (P < 0.05) increases in risk with updated dosimetry for D m in the category of 20 to 29.9 Gy and V 20 in the category of 30% to 79.9%. When changes in the linear dose-response relationship for D m were assessed, the slopes of the dose response were steeper (P < 0.001) with updated dosimetry. Changes were primarily observed among individuals with chest-directed RT with prescribed doses ≥ 20 Gy., Conclusion: These findings present a methodological advancement in heart RT dosimetry with improved estimates of RT-related late cardiac disease risk. While results are broadly consistent with our prior study, we report that, with updated cardiac dosimetry, risks of cardiac disease are significantly higher in two dose and volume categories and slopes of the Dm-specific RT-response relationships are steeper. These data support the use of contemporary RT to achieve lower heart doses for pediatric patients, particularly those requiring chest-directed RT., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aimed to assess the prognostic value of baseline disease distribution for patients with the secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy and radiation (RT). 44 patients with secondary CNS DLBCL were reviewed. Twenty patients had leptomeningeal disease (LMD), and 24 had localized/targetable disease (LTD). Of 8 patients who received stem cell transplantation (SCT) after RT, 6 had LTD with a complete or partial response after RT. Median time to CNS relapse after RT was 10.1 months; 3/24 patients with LTD and 5/15 with LMD had CNS relapse. The median overall survival (OS) was 8 and 20 months for patients with LMD and LTD, respectively ( p  = 0.20). On multivariable analysis, LTD, receipt of SCT, and response after RT were associated with better OS and CNS-disease-free survival. Patients with localized secondary CNS DLBCL may benefit from RT serving as a bridge to SCT.

Purpose: Primary mediastinal B cell lymphoma (PMBCL) is a highly curable subtype of non-Hodgkin lymphoma that is diagnosed predominantly in adolescents and young adults. Consequently, long-term treatment-related morbidity is critical to consider when devising treatment strategies that include different chemoimmunotherapy strategies with or without radiation therapy. Furthermore, adaptive approaches using the end-of-chemotherapy (EOC) positron emission tomography (PET)/computed tomography (CT) scanning may help to determine which patients may benefit from additional therapies. We aimed to develop evidence-based guidelines for treating these patients., Methods and Materials: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the PubMed database. The ARS expert committee, composed of radiation oncologists, hematologists, and pediatric oncologists, developed consensus guidelines using the modified Delphi framework., Results: Nine studies met the full criteria for inclusion based on reporting outcomes on patients with primary mediastinal B cell lymphoma with EOC PET/CT response scored with the 5-point Deauville scale. These studies formed the evidence for these guidelines in managing patients with PMBCL according to the EOC PET response, including after a 5-point Deauville scale of 1 to 3, 4, or 5, and for patients with relapsed and refractory disease. The expert group also developed guidance on radiation simulation, treatment planning, and plan evaluation based on expert opinion., Conclusions: Various treatment approaches exist in the management of PMBCL, including different chemoimmunotherapy regimens, the use of consolidative radiation therapy, and adaptive approaches based on EOC PET/CT response. These guidelines can be used by practitioners to provide appropriate treatment according to different disease scenarios., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study's objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T-related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration., (© 2021 by The American Society of Hematology.)

Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy-associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy-associated toxicities., (© 2021 by The American Society of Hematology.)

We addressed the prognostic impact of cell-of-origin (COO), MYC and Bcl-2 overexpression as well as isolated MYC rearrangement among 111 patients with limited stage diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiation therapy (RT) after a metabolic complete response to immunochemotherapy. With a median follow-up of 31.1 months (95% CI 27.4 - 34.8), 4 relapses occurred. The 3-year progression free survival (PFS), overall survival (OS), and loco-regional relapse free survival (LRFS) for the cohort were 95%, 96%, and 100%, respectively. There were no differences in OS, PFS, or LRFS based on COO or MYC/Bcl-2 dual expression (DE). Similarly, patients with MYC translocations without BCL2 or BCL6 rearrangements did not have worse outcomes. Consolidative RT produced excellent local control, regardless of DLBCL biology, with one late in-field failure.

This guideline for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) by the American Radium Society was developed by a multidisciplinary expert panel of medical, pediatric, and radiation oncologists convened to formulate guidelines for evaluation and treatment. The guideline development was based on an in-depth literature review and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of the recommendations by the panel. Given the scarcity of compelling data for strong recommendations for a rare lymphoma that has been shown to be more indolent than classical Hodgkin lymphoma, in instances where evidence is not available or equivocal, expert opinion guided the recommendations. Four clinical variants exemplify common scenarios and represent the consensus recommendations for patients with nodular lymphocyte Hodgkin lymphoma. A summary of the available published literature is also presented.

Purpose: We report the long-term results of a prospective trial conducted to determine the efficacy and safety of radiation therapy (RT) alone in treating localized mucosa-associated lymphoid tissue (MALT) lymphoma., Methods and Materials: Patients with localized MALT lymphoma were eligible and treated with involved field RT to doses of 24 to 39.6 Gy. Relapse-free survival (RFS) was the primary endpoint. Kaplan-Meier analysis was used to estimate RFS, progression-free survival (PFS), and overall survival (OS) defined from time of study entry. Preplanned subgroup analyses were performed based on site of involvement., Results: From 2000 to 2012, 75 patients were accrued; 73 received protocol-specified RT. Median follow-up was 9.8 years. Thirty-four patients had gastric MALT, 17 orbital, 13 head and neck nonorbit, 4 skin, and 5 disease of other sites. Thirteen of 34 patients with gastric MALT were Helicobacter pylori positive at the time of initial diagnosis and underwent 1 to 3 courses of triple antibiotic therapy. All gastric MALT patients had documented persistent MALT without H. pylori on endoscopy before enrollment in the study. All patients achieved a complete response with a median time of 3 months. Eleven patients (15%) had disease relapse, 9 of which were at sites outside the RT field with median time to progression of 38.3 months. Median PFS was 17.5 years, and median RFS and OS were not reached. The 10-year relapse-free rate was 83% (95% confidence interval [CI], 74%-93%). The 10-year PFS rate was 71% (95% CI, 60%-84%). The 10-year OS rate was 86% (95% CI, 77%-96%). RFS, PFS, and OS did not differ by disease site (P = .17, .43, and .50, respectively). All relapses were successfully salvaged. One patient developed metastatic gastric adenocarcinoma and was found to also have recurrent MALT on biopsy. Otherwise, all relapsed patients were alive without evidence of disease at last follow-up, and no patient died of MALT lymphoma. Sixty-seven patients (92%) experienced acute toxicity during radiation, all of which were grade 1 and 2, with only 1 grade 3 toxicity. Twenty-two patients (30%) experienced late toxicity, with only 1 grade 3 toxicity., Conclusions: This prospective study confirms that RT for MALT lymphoma provides excellent long-term RFS with acceptable rates of toxicity. Current efforts are focused on RT de-escalation in an effort to further avoid treatment-related morbidity. CLINICALTRIALS.GOV: NCT04465162., (Copyright © 2020. Published by Elsevier Inc.)

CAR T-cell therapy has revolutionized the treatment approach to patients with relapsed/refractory hematologic malignancies; however, there continues to be opportunity for improvement in treatment toxicity as well as response durability. Radiation therapy can play an important role in combined modality treatments for some patients undergoing CAR T-cell therapy in various clinical settings. In this review, we discuss the current evidence for RT in the setting of CAR T-cell therapy for patients with hematologic malignancies and propose potential opportunities for future investigation of RT and CAR T-cell treatment synergy. Future research frontiers include investigation of hypotheses including radiation priming of CAR T-cell mediated death, pre-CAR T-cell tumor debulking with radiation therapy, and selection of high risk patients for early radiation salvage after CAR T cell therapy., Competing Interests: LN: Honorarium: Bayer, Celgene, Genentech, Gilead/Kite, Janssen, Juno, Novartis, TG Therapeutics, and Spectrum Therapeutics; Research: Celgene, Genentech, Janssen, TG Therapeutics, and Karus Therapeutics. SN: Research support from Kite/Gilead, Merck, BMS, Cellectis, Poseida, Karus, Acerta, and Unum Therapeutics. Advisory Board Member/Consultant for Kite/Gilead, Merck, Celgene, Novartis, Unum Therapeutics, Pfizer, Precision Biosciences, Cell Medica, Calibr, Allogene, Incyte, and Legend Biotech. CP: Research support from Merck. The remaining 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 © 2021 Fang, Gunther, Wu, Dabaja, Nastoupil, Ahmed, Neelapu and Pinnix.)

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity, with limited data on the outcome in the relapsed/refractory setting. We evaluated the outcome of all patients diagnosed between 04/1979 and 01/2019 with relapsed or progressive NLPHL after initial active therapy at two institutions, refractory disease being defined as lack of response to treatment and/or relapse within three months of treatment. NLPHL patients with histological evidence of transformation at time of first relapse or progression were excluded. In total, 69 patients with recurrent NLPHL were included in the study. After a median follow-up after initial diagnosis of 14 years (range, 0·5-46 years), median progression-free survival after front-line treatment (PFS-1) was four years. Second-line therapy included chemotherapy in 28 (41%) patients, biological therapy (rituximab, lenalidomide or brentuximab vedotin) in 14 (20%), high-dose chemotherapy followed by autologous stem cell transplant in 14 (20%) and radiation therapy (RT) alone in 10 (15%). The five-year PFS after second-line therapy (PFS-2) was 68% [95% confidence interval (CI), 54-79%] but the five-year overall survival (OS) after second-line therapy (OS-2) remained excellent, at 94% (95% CI, 85-99%). Due to excellent outcome in case of recurrence, studies aimed at characterizing its biology to guide therapy de-escalation are needed., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Background and Purpose: Radiation therapy is a risk factor for late cardiac disease in childhood cancer survivors. Several pediatric cohort studies have established whole heart dose and dose-volume response models. Emerging data suggest that dose to cardiac substructures may be more predictive than whole heart metrics. In order to develop substructure dose-response models, the heart model previously used for pediatric cohort dosimetry needed enhancement and substructure delineation., Methods: To enhance our heart model, we combined the age-scalable capability of our computational phantom with the anatomically-delineated (with substructures) heart models from an international humanoid phantom series. We examined cardiac volume similarity/overlap between registered age-scaled phantoms (1, 5, 10, and 15 years) with the enhanced heart model and the reference phantoms of the same age; dice similarity coefficient (DSC) and overlap coefficient (OC) were calculated for each matched pair. To assess the accuracy of our enhanced heart model, we compared doses from computed tomography-based planning (ground truth) with reconstructed heart doses. We also compared doses calculated with the prior and enhanced heart models for a cohort of nearly 5000 childhood cancer survivors., Results: We developed a realistic cardiac model with 14-substructures, scalable across a broad age range (1-15 years); average DSC and OC were 0.84 ± 0.05 and 0.90 ± 0.05, respectively. The average percent difference between reconstructed and ground truth mean heart doses was 4.2%. In the cohort dosimetry analysis, dose and dose-volume metrics were approximately 10% lower on average when the enhanced heart model was used for dose reconstructions., Conclusion: We successfully developed and validated an anatomically realistic age-scalable cardiac model that can be used to establish substructure dose-response models for late cardiac disease in childhood cancer survivor cohorts., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

CT-guided treatment delivery can improve target localization in mediastinal lymphoma patients treated with "butterfly" intensity-modulated radiotherapy and deep-inspiration breath hold. Although daily CT imaging adds additional radiation exposure, its use may be justified given the greater normal tissue sparing enabled by PTV margin reduction., (Copyright © 2020. Published by Elsevier B.V.)