Therapies for diseases of the bone marrow are rapidly evolving with recent improvements in multi-agent chemotherapeutic regimens, immunotherapies, targeted agents, and hematopoietic stem cell transplants. In the recent era of biologically directed treatments and cellular therapies, long-term remissions are possible even in patients with disease progression following salvage systemic therapies or transplantation. Multidisciplinary discussion with medical oncologists is imperative to review the perceived treatment intent and the myriad of available systemic options for patients. Many of the malignant cells in bone marrow diseases are exquisitely sensitive to radiotherapy. In this chapter, we review how this radiodensity can be harnessed in the palliative setting where ultra-low doses of radiotherapy can achieve the desired goals for patients with leukemia and multiple myeloma. We review the available literature on the use of radiotherapy for local manifestations of these diseases and consider commonly encountered clinical scenarios.

Recent improvements in chemotherapies, targeted agents, hematopoietic stem cell transplants, and cellular therapies have revolutionized treatment paradigms for patients with lymphomas. Even in the relapsed or refractory setting, contemporary treatment options are delivered with a curative intent and routinely lead to lasting remissions. While such therapies have improved overall outcomes, they have increasingly led to a wide variety of presentations of recurrent tumors in need of palliation. In this chapter, we discuss the use of radiotherapy in the palliation of symptoms for patients with non-Hodgkin lymphomas, Hodgkin lymphomas, and cutaneous T-cell lymphomas. Lymphomas are frequently exquisitely radiosensitive, and low doses of radiotherapy may be used for palliation. We review the available literature on these topics and draw particular attention to commonly encountered clinical scenarios.

Purpose To assess whether a radiotherapy (RT) dose affects response in bulky tumors in relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). Methods Data from r/r DLBCL patients treated with salvage- or palliative-intent RT (2008-2020) at a single institution were examined. Index lesion size ≥7.5 cm was defined as bulky. Equivalent doses in 2 Gray (Gy) fractions (EQD2) were calculated to compare doses between conventional and hypofractionated (HF, ≥2.5 Gy/fraction) schemes. Objective response rates (ORR) were compared using non-parametric Mann-Whitney U test or Kruskal-Wallis tests with Dunn's multiple comparison corrections. Freedom from local progression (FFLP) was assessed using Kaplan-Meier and Cox proportional hazard regression analyzes. Results 183 courses of 151 unique patients were included (salvage: 37%, palliative: 63%). Non-bulky and bulky tumors were irradiated in 109 (60%) and 74 (40%) courses, respectively. Median EQD2 was 33 Gy (IQR=23-39 Gy) with HF in 84 (46%) cases. Of those with post-RT imaging (80%), the ORR was 59% with a trend towards worsened ORR in bulky tumors (50% vs. 65%, p=0.077). For bulky tumors, RT regimens with EQD2s >30 Gy were associated with better ORR (≤30 Gy vs. >30 Gy: 27% vs. 64%, p=0.0073), whereas a lower EQD2 cut-off was sufficient for non-bulky tumors (≤20 Gy vs. >20 Gy: 38% vs. 75%, p=0.0011). On multivariable regression, bulky tumor size was associated with worsened FFLP (HR=2.07, 95% CI=1.16-3.68, p=0.014), while high EQD2s >30 Gy were associated with better FFLP (HR=0.48, 95% CI=0.25-0.93, p=0.031). Bulky tumors treated with EQD2s ≤30 Gy had the lowest median FFLP (4.0 months), while EQD2s >30 Gy had an unreached median FFLP (p=0.0047). Conclusions Bulky r/r DLBCL tumors were associated with less favorable tumor control outcomes in the salvage and palliative settings. RT regimens with higher EQD2s (>30 Gy) should be considered if durable local control of bulky tumors is desired.

Background and purpose: CD19-targeting chimeric antigen receptor T-cell (CART) therapy is a promising treatment for relapsed/refractory non-Hodgkin lymphoma, but most patients experience post-CART progression. We describe our institutional experience of salvage radiotherapy (SRT) in this setting. Materials and methods: Of 94 patients who received CART therapy from 2018 to 2020, 21 received SRT for post-CART progression. Patients were divided into two groups: locoregional disease (n = 9 [43 %], all disease encompassable within an RT field) and advanced disease (n = 12 [57 %]). Patterns of failure, progression-free survival (PFS), overall survival (OS), and toxicity were assessed. Results: Median time from CART infusion to SRT was 4.0 months (range, 0.6–11.5 months). In the locoregional disease group, 8/9 patients (89 %) were treated with comprehensive SRT to a median dose of 37.5 Gy in a median of 15 fractions. In the advanced disease group, all patients (n = 12) were treated with focal SRT to a median dose of 20.8 Gy in a median of 5 fractions. Median follow-up post-SRT was 15.2 months. In-field response was observed in 8/9 (89 %) in the locoregional disease and 8/9 (89 %) evaluable patients in the advanced disease groups. 17/18 evaluable patients (94 %) patients experienced post-SRT progression, all with a distant component. Median OS was 7.4 months; 21 months for locoregional disease versus 2.4 months for advanced disease (p = 0.0002). Median PFS was 1.1 month, and similarly poor regardless of group. No grade ≥ 3 toxicities occurred. Conclusions: SRT post-CART therapy appears safe with encouraging in-field response but high rates of out-of-field progression, even for those presenting with locoregional disease, highlighting the need for integration of novel systemic agents.

Introduction: Bridging radiotherapy (BRT) may be used prior to chimeric antigen receptor T-cell (CAR T) infusion for tumor cytoreduction, symptom palliation, and lymphodepletion. Case series on BRT are small and typically limited to single-institution reports. Herein, we report a multi-institutional analysis of the use of BRT prior to CD19-targeting CAR T therapy for relapsed/refractory B-cell lymphomas, with a focus on BRT characteristics, toxicity, and disease outcomes. Methods: We retrospectively analyzed 77 patients with diffuse large B-cell lymphoma (n=64, 83%), primary mediastinal B-cell lymphoma (n=11, 14%), mantle cell lymphoma (n=1, 1%), and T-cell/histiocyte rich large B-cell lymphoma (n=1, 1%) who underwent CAR T therapy between 2018 and 2020 at 4 academic institutions. All received BRT within 1 month prior to leukapheresis up until CAR T infusion. BRT toxicities were graded with CTCAE v5.0, cytokine release syndrome (CRS) per ASTCT, and immune effector cell-associated neurotoxicity syndrome (ICANS) using either ASTCT or CTCAE v5.0. PET/CT response post-CAR T therapy was determined according to Lugano criteria. Patterns of failure were classified with respect to both BRT fields (in field, out of field, or both) and immediate pre-CAR T sites of disease (prior site, new site, or both). Progression-free survival (PFS) and overall survival (OS), measured from CAR T infusion, were estimated using the Kaplan-Meier method and modeled using Cox regression. Results: Patients received axicabtagene ciloleucel (axi-cel; n=56, 73%), tisagenlecleucel (tisa-cel; n=20, 26%), and brexucabtagene autoleucel (n=1, 1%). Median age was 64 years (range, 24-81). Majority (n=41, 53%) were female and had advanced stage III/IV relapsed/refractory disease (n=60, 78%). ECOG performance status was 0/1/2/3 for 18 (24%), 41 (55%), 13 (17%), and 3 (4%), respectively. Median prior lines of therapy was 3 (range, 1-6). Extranodal disease was present in 49/75 (65%), central nervous system (CNS) involvement in 8 (10%), and bulky disease (lesion ≥7.5 cm) in 41/69 (59%). Systemic bridging therapy, excluding steroids, was given to 27 patients (35%). Median interval from leukapheresis to BRT start and from BRT end to CAR T infusion were 7 days (interquartile range [IQR], 3-12) and 12 days (IQR, 9-17), respectively. 19 patients (25%) received BRT to more than one anatomic site. BRT was delivered to the abdomen/pelvis (n=39, 51%), head/neck (n=18, 23%), thorax (n=11, 14%), extremity/soft tissue (n=10, 13%), CNS (n=6, 8%), spine/paraspinal region (n=6, 8%), and axilla (n=6, 8%). Median BRT dose was 26 Gy (range, 4-45), median fraction dose 3 Gy (range, 1.3-15), and most common regimen 20 Gy in 5 fractions. 26 patients (34%) received BRT to all active lesions. No grade ≥3 BRT toxicities were observed. Grade ≥3 CRS occurred in 5 patients (6%; 4 Grade 3 and 1 Grade 4). Grade ≥3 ICANS occurred in 17 patients (22%; 13 Grade 3 and 4 Grade 4), including 16/56 (29%) who received axi-cel and 1/20 (5%) who received tisa-cel. 25 patients (32%) received tocilizumab and 30 (39%) received steroids for CAR T toxicity. At a median of 33 days (IQR, 29-66) to first restaging PET/CT, overall response rate (ORR) was 83% (complete response 37/75, partial response 25/75). At a median follow up of 31.3 months (95% CI, 24.3 - 33.6), 44 patients (57%) had experienced disease progression and 41 (53%) had died. Patterns of failure were detailed for 41 patients and included within the BRT field only (n=4, 10%,) out of field only (n=25, 61%), and both (n=12, 29%). Failure occurred at immediate pre-CAR T sites only (n=5, 12%), new sites only (n=15, 37%) and both (n=21, 51%). 1- and 2-year OS rates were 59% and 48%. 1- and 2-year PFS rates were 41% and 35% (Figure 1). On multivariable analysis, age ≥65 (hazard ratio [HR] 1.9, p=0.040), CNS involvement (HR 4.5, p=0.0028), ≥3 prior lines of therapy (HR 2.1, p=0.0095), and bulky disease (HR 2.4, p=0.0063) were associated with inferior PFS. Conclusions: In this multi-institutional study, patients receiving BRT frequently had bulky disease yet experienced favorable ORR, PFS, and OS after CAR T therapy. There were no serious BRT toxicities and acceptable rates of CAR T toxicity. Isolated failure within the BRT field alone was uncommon. Future studies are needed to better define patient selection criteria for BRT versus other bridging therapies, as well as clarify the utility of "debulking” BRT prior to CAR T therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Purpose One significant advantage of proton therapy is its ability to improve normal tissue sparing and toxicity mitigation, which is relevant in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Here, we report our institutional experience and dosimetric results with adjuvant proton radiation therapy (PRT) versus intensity-modulated radiotherapy (IMRT) for Human Papilloma Virus (HPV)-associated OPSCC. Materials and Methods This was a retrospective, single institutional study of all patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019. Each patient had a treatment-approved equivalent IMRT plan to serve as a reference. Endpoints included dosimetric outcomes to the organs at risk (OARs), local regional control (LRC), progression-free survival (PFS), and overall survival (OS). Descriptive statistics, a 2-tailed paired t test for dosimetric comparisons, and the Kaplan-Meier method for disease outcomes were used. Results Fifty-three patients were identified. Doses delivered to OARs compared favorably for PRT versus IMRT, particularly for the pharyngeal constrictors, esophagus, larynx, oral cavity, and submandibular and parotid glands. The achieved normal tissue sparing did not negatively impact disease outcomes, with 2-year LRC, PFS, and OS of 97.0%, 90.3%, and 97.5%, respectively. Conclusion Our study suggests that meaningful normal tissue sparing in the postoperative setting is achievable with PRT, without impacting disease outcomes.

Purpose: Combined modality therapy with multiagent chemotherapy and radiation therapy is a standard treatment option for aggressive mediastinal non-Hodgkin lymphomas (AMNHLs); however, concerns regarding acute and late radiation toxicities have fueled an effort to use systemic therapy alone. The use of proton therapy (PT) is a promising treatment option, but there are still limited data regarding clinical outcomes with this treatment modality. In this Particle Therapy Cooperative Group lymphoma subcommittee collaboration, we report outcomes of patients with AMNHL treated with pencil-beam scanning PT or double-scatter PT after chemotherapy. Methods and Materials: This was a multi-institutional retrospective observational cohort study of patients with AMNHL treated with PT following chemotherapy between 2011 and 2021. Progression-free survival (PFS), local recurrence–free survival (LRFS), and overall survival (OS) rates were estimated with the Kaplan-Meier method. PT toxicity was graded by the Common Terminology Criteria for Adverse Events version 5.0. A 2-tailed paired t test was used for dosimetric comparisons. Results: Twenty-nine patients were identified. With a median follow-up time of 4.2 years (range, 0.2-8.9 years), the estimated 5-year PFS for all patients was 93%, 5-year LRFS was 96%, and estimated 5-year OS was 87%. Maximum acute grade 1 (G1) toxicities occurred in 18 patients, and 7 patients had maximum G2 toxicities. No G3+ radiation-related toxicities were observed. Average mean lung dose and lung V20 Gy were lower for patients treated with pencil-beam scanning PT compared with double-scatter PT (P = .016 and .006, respectively), while patients with lower mediastinal disease had higher doses for all evaluated dosimetric heart parameters. Conclusions: PT after chemotherapy for patients with AMNHL resulted in excellent outcomes with respect to 5-year PFS, LRFS, and OS without high-grade toxicities. Future work with larger sample sizes is warranted to further elucidate the role of PT in the treatment of AMNHL.

PURPOSE:Although dose de-escalation is one proposed strategy to mitigate long-term toxicity in human papillomavirus associated oropharyngeal cancer, applying more stringent normal tissue constraints may be a complementary approach to further reduce toxicity. Our study demonstrates that in a postoperative setting, improving upon nationally accepted constraints is achievable and leads to reductions in normal tissue complication probabilities (NTCP) without compromising disease control.METHODS AND MATERIALS:We identified 92 patients at our institution between 2015 and 2019 with p16+ oropharyngeal cancer who were treated with adjuvant volumetric modulated arc therapy. We included patients treated to postoperative doses and standard volumes (including bilateral neck). Doses delivered to organs at risk were compared with recommended dose constraints from a recent cooperative group head and neck cancer trial of radiation therapy to 60 Gy. We applied validated and published NTCP models for dysphagia, dysgeusia, esophagitis, oral mucositis, and xerostomia relevant to oropharyngeal cancer.RESULTS:Achievable and delivered mean doses to most normal head and neck tissues were well below national recommended constraints. This translates to notable absolute NTCP reductions for salivary flow (10% improvement in contralateral parotid, 35% improvement in submandibular gland), grade ≥ 2 esophagitis (23% improvement), grade ≥ 3 mucositis (17% improvement), dysgeusia (10% improvement), and dysphagia (8% improvement). Locoregional control at a median follow-up of 26.3 months was 96.7%, with only 3 patients experiencing locoregional recurrence (1 local, 2 regional).CONCLUSIONS:Modern radiation therapy planning techniques allow for improved normal tissue sparing compared with currently established dose constraints without compromising disease control. These improvements may lead to reduced toxicity in a patient population expected to have favorable long-term outcomes. Stricter constraints can be easily achieved and should be used in conjunction with other evolving efforts to mitigate toxicity.

The recently identified bilateral macroscopic tubarial salivary glands present a potential opportunity for further toxicity mitigation for patients receiving head and neck radiotherapy. Here, we show superior dosimetric sparing of the tubarial salivary glands with proton radiation therapy (PRT) compared to intensity-modulated radiotherapy (IMRT) for patients treated postoperatively for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). This was a retrospective, single institutional study of all patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019. Each patient had a treatment-approved, equivalent IMRT plan to serve as a reference. The main end point was dose delivered to the tubarial salivary glands by modality, assessed via a 2-tailed, paired t-test. We also report disease outcomes for the entire cohort, via the Kaplan-Meier method. Sixty-four patients were identified. The mean RT dose to the tubarial salivary glands was 23.6 Gy (95% confidence interval (CI) 21.7 to 25.5) and 30.4 Gy (28.6 to 32.2) for PRT and IMRT plans (p < 0.0001), respectively. With a median follow-up of 25.2 months, the two-year locoregional control, progression-free survival and overall survival were 97.8% (95% CI 85.6% to 99.7%), 94.1% (82.8% to 98.1%) and 98.1% (87.4% to 99.7%), respectively. Our study suggests that meaningful normal tissue sparing of the recently identified tubarial salivary glands is achievable with PRT. The apparent gains with PRT did not impact disease outcomes, with only 1 observed locoregional recurrence (0 local, 1 regional). Further studies are warranted to explore the impact of the improved dosimetric sparing of the tubarial salivary glands conveyed by PRT on patient toxicity and quality of life.

Objectives: To assess the prognostic significance of oligometastatic versus polymetastatic disease in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), and to evaluate the impact of definitive tumor directed therapy on the survival outcomes for patients with oligometastatic disease when compared to systemic therapy . Materials and Methods: This was a retrospective observational cohort study of patients with HPV-associated OPSCC who developed distant metachronous metastatic disease after undergoing initial primary surgical management from 2008 to 2017. We classified patients based on the extent of metastatic disease [Oligometastatic (<= 5 metastases) and polymetastatic (>5 metastases)], and the initial treatment of metastatic disease [definitive tumor directed therapy (all metastases treated with surgery or radiotherapy) versus upfront systemic therapy]. Results: Among 676 patients undergoing primary surgical management for HPV-associated OPSCC, 39 patients (5.8%) developed metastases after a median follow-up of 29.6 months (range 4.5-127.0). Of the 34 metastatic patients who met study criteria, 26 (76.5%) were oligometastatic and 8 (23.5%) were polymetastatic. Oligometastatic patients had improved median overall survival (OS) compared to polymetastatic patients (47.9 vs. 22.7 months, p = 0.036). For oligometastatic patients, definitive tumor directed therapy was associated with an improved median progression free survival (not reached vs 6.13 months, p = 0.001) and median OS (not reached vs 40.7 months, p = 0.004). Conclusion: In a cohort of patients surgically treated for HPV-associated OPSCC, metachronous metastatic disease was uncommon and, in most cases, considered oligometastatic. Oligometastasis portends a favorable prognosis and definitive tumor directed therapy may be associated with improved overall survival in these patients. Future multi-institutional efforts are warranted to further demonstrate the impact of definitive tumor directed therapy on disease outcomes.

Financial conflicts of interest (FCOIs) could bias the potentially practice-changing oncologic randomized clinical trials (RCTs) of tomorrow. This investigation characterized the FCOIs of the principal investigators (PIs) of all currently accruing trials of the four (adult) cooperative groups of the National Clinical Trials Network. For our study, the PI list was first compiled, and each name was then searched in the CMS Open Payments database. For each transaction (general payments (GPs) or research funding (RF)), the amount/number/source of payments was recorded. Results showed that from 2014 to 2019, the 91 PIs collectively accepted nearly one-third of a billion dollars ($10 477 023 GPs and $320 096 233 RF). The mean and median GP was $6505 and $945, respectively, and $301 693 and $49 824 RF, respectively. Multivariable Gamma regression analysis revealed that higher GP sums were associated with RCTs involving any type of systemic therapy, and higher RF sums with medical oncologist PIs, trials with phase III components, and RCTs involving radiotherapy (P < .05 for all). Both higher-volume GPs and RF were predicted by PIs having accepted payment(s) from the manufacturer of the drug utilized in their RCT (P < .001 GP, P = .008 RF). Taken together, the main message of this investigation is that FCOIs may be particularly high in PIs of phase III systemic therapy trials, especially if the PI accepted payments from the manufacturer of the drug utilized in their trial. Such RCTs should be thoroughly scrutinized by medical journals, the FDA, and insurance companies for potential "industry bias" that could influence the integrity of their conclusions.

Recent improvements in chemoimmunotherapies, targeted agents, hematopoietic stem cell transplants, and cellular therapies have revolutionized treatment paradigms for patients with diffuse large B-cell lymphoma (DLBCL). Even in the relapsed or refractory setting, contemporary treatment options are delivered with curative intent and can lead to lasting remissions. Although such therapies have improved overall outcomes, they have increasingly led to a wide variety of presentations of recurrent tumors in need of palliation. Here, we review the use of radiotherapy (RT) in the palliation of DLBCL. We draw particular attention to the evolving role for hypofractionated RT and low-dose RT for DLBCL. We review the available literature on these topics and focus on commonly encountered clinical scenarios.

PurposeRadiation therapy (RT) with doses ranging from 24 Gray (Gy) to 40 Gy is a proven treatment modality for indolent orbital adnexal lymphoma (IOAL), but recently the use of low dose RT (LDRT, defined as 2 Gy x 2 fractions) has become a notable alternative. However, limited data exists comparing outcomes following LDRT to moderate-dose RT (MDRT, RT dose 4 – 36 Gy). We present a single institution retrospective analysis comparing outcomes of patients with IOALs following LDRT or MDRT.MethodsA total of 36 patients treated with 38 consecutive courses of RT were identified; LDRT was delivered for 14 courses and MDRT for 24 courses. Overall response rates (ORR) were recorded according to Deauville or RECIST criteria with a response characterized as a complete response (CR) or partial response. Local control (LC), orbital control (OC), and overall survival (OS) rates were estimated with the Kaplan-Meier method. RT toxicity was graded per CTCAEv5 and compared with the Fisher’s exact test.ResultsMedian follow-up time was 29 months (m) (range, 4-129m), and median MDRT dose used was 24 Gy (range 21-36 Gy). Overall response rates (ORR) were 100% (CR 50%) and 87.5% (CR 58.3%) following LDRT and MDRT, respectively. OS at 2 years was 100% and 95% for the LDRT and MDRT groups, respectively (p=0.36). LC rates at 2 years was 100% for both LDRT and MDRT groups and at 4 years was 100% and 89% for the LDRT and MDRT groups, respectively (p=0.56). The 4-year OC rate (including both ipsilateral and contralateral relapses) was 80% and 85% for the LDRT and MDRT groups, respectively (p=0.79). No patient required treatment with RT to a previously irradiated orbit. Acute toxicities were reported following 6 LDRT courses compared to 20 MDRT courses (p=.014). No Grade 3 or higher acute toxicities occurred in either group. Late toxicities were reported following 2 LDRT courses compared to 10 MDRT courses (p=0.147).ConclusionsLDRT produced similar ORR, LC, OC, and OS rates compared to MDRT with fewer acute and minimal late toxicities reported. Future multi-center studies with larger patient numbers are warranted to show significant associations.

Background: For malignant pleural mesothelioma (MPM), the benefit of resection, as well as the optimal surgical technique, remain controversial. In efforts to better refine patient selection, this retrospective observational cohort study queried the National Cancer Database in an effort to quantify and evaluate predictors of 30and 90-day mortality between extrapleural pneumonectomy (EPP) and pleurectomy/ decortication (P/D), as well as nonoperative management. Methods: After applying selection criteria, cumulative incidences of mortality by treatment paradigm were graphed for the unadjusted and propensity-matched populations, as well as for six a priori age-based intervals (<= 60, 61-65, 66-70, 71-75, 76-80, and >= 81 years). The interaction between age and hazard ratio (HR) for mortality between treatment paradigms was also graphed. Cox multivariable analysis ascertained factors independently associated with 30and 90-day mortality. Results: Of 10,723 patients, 2,125 (19.8%) received resection (n=438 EPP, n=1,687 P/D) and 8,598 (80.2%) underwent nonoperative management. The unadjusted 30/90-day mortality for EPP, P/D, and all operated cases was 3.0%/8.0%, 5.4%/14.1%, and 4.9%/12.8%, respectively. There were no short-term mortality differences between EPP and P/D following propensity-matching, within each age interval, or between age subgroups on interaction testing (P 0.05 for all). Nonoperative patients had a crude 30and 90-day mortality of 9.9% and 24.6%, respectively. Several variables were identified as predictors of short-term mortality, notably patient age (HR 1.022, P<0.001), Charlson-Deyo comorbidity index (HR 1.882, P<0.001), receipt of treatment at high-volume centers (HR 0.834, P=0.032) and induction chemotherapy (HR 1.735, P=0.025), among others. The patient (yearly) incremental increase in age conferred 2.0% (30 day) and 2.2% (90 day) increased risk of mortality (P<0.001). Conclusions: Quantitative estimates of age-associated 30and 90-day mortality of EPP and P/D should be considered when potentially operable patients are counseled regarding the risks and benefits of resection.

CD19-targeting chimeric antigen receptor T-cell (CART) therapy has emerged as a promising treatment for relapsed/refractory non-Hodgkin lymphoma (r/rNHL), culminating in 2 FDA-approved therapies, tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). At our institution, axi-cel is uniformly delivered as an inpatient, while tisa-cel is being explored as an outpatient regimen. Sequencing radiation therapy (RT) prior to CART appears safe and feasible, and may be used to decrease toxicity in select patients (LaRiviere et al., IJROBP 2019). This study's purpose was to review the hospitalization requirement for commercial CART infusion, the incidence and duration of unplanned hospitalizations following CART, and the total hospitalization days required for patients receiving CART. We also sought to explore the impact of RT on unplanned hospitalizations and the overall hospital burden. 31 patients receiving commercial tisa-cel (n=13) or axi-cel (n=18) between 8/2018 and 2/2019 for r/rNHL were identified. Patients were divided into two groups: RT-CART (n=5) for those who received RT<30d prior to CART infusion and CART (n=26) for those with remote RT≥30d (n=7) or no prior RT (n=19). Unplanned hospitalizations were defined as post-CART-infusion in the tisa-cel group and re-hospitalizations in the axi-cel group. All axi-cel patients were hospitalized for infusion as planned. 12/13 tisa-cel patients received infusion as an outpatient. 8/12 tisa-cel outpatients did not require an unplanned hospitalization following infusion. The mean total duration of the infusion admission was 20d [18 and 22d] for RT-CART patients and 24d [95% CI 16-32d] for the CART group. The duration of infusion admission for those receiving axi-cel was 20d [18 and 22d] for the RT-CART group and 27d [18-36d] for the CART group. In the CART group, 5 patients (31%) and 4 patients (40%) receiving axi-cel and tisa-cel, respectively, required an unplanned hospitalization. 0/3 tisa-cel patients and 0/2 axi-cel patients in the RT-CART group required an unplanned hospitalization. Total mean hospitalization duration for axi-cel patients, including both infusion-related and unplanned hospitalizations, was 20d [18 and 22d] for RT-CART patients compared to 34d [18-50d] for the CART group. We report 8 patients receiving CART, with or without RT, as a complete outpatient regimen. No RT-CART patients required an unplanned hospitalization, irrespective of CART product. While this study was underpowered to test associations between groups and outcomes, it invokes an intriguing question as to whether sequencing RT and CART may decrease the incidence of unplanned hospitalizations and the overall duration of admissions. Future work should be undertaken to better understand the potential impact of RT on CART-related toxicities and hospitalization requirements.

Females only account for a minority of malignant pleural mesothelioma (MPM) diagnoses, but may experience differential survival relative to men. It is unclear if differential receipt of treatment may be contributory. In this National Cancer Database analysis, we found that although surgery and chemotherapy are disproportionately underutilized in female patients with MPM, female gender is independently associated with improved survival relative to males. Background: Despite accounting for a minority of malignant pleural mesothelioma (MPM) diagnoses, females may experience differential survival relative to males. It is unclear if there are gender-based differences in receipt of treatment or disease-related outcomes for patients with MPM. We therefore utilized the National Cancer Database (NCDB) to assess patterns-of-care and overall survival (OS) among patients with MPM by gender. Materials and Methods: Patients with histologically confirmed MPM treated from 2004 to 2013 were identified from the NCDB. The association between female gender and OS was assessed using multivariable Cox proportional hazards models with propensity score matching. Patterns-of-care were assessed using multivariable logistic regression. The overall treatment effect was tested in subsets of patients by treatment strategy, histology, and clinical stage. Results: A total of 18,799 patients were identified, of whom 14,728 (78%) were male and 4071 (22%) were female. Females were statistically more likely to present at a younger age, with fewer comorbidities, and with epithelioid histology. Despite these favorable prognostic features, women were less likely to receive surgery (P <= .001) or chemotherapy (P <= .001) compared with males. On multivariable analysis, female gender was associated with improved OS (hazard ratio, 0.83; 95% confidence interval, 0.80-0.86; P <= .001). Gender-based survival differences were seen across all stages, but only among patients with epithelioid (P <= .001) and not biphasic (P = .17) or sarcomatoid (P = 1.00) histology. Conclusions: Surgery and chemotherapy are disproportionately underutilized in female patients with MPM. Despite this concerning disparity, female gender is independently associated with improved survival relative to males. Further research to understand factors that lead to gender disparities in MPM is warranted. (C) 2020 Elsevier Inc. All rights reserved.

For the past 100 years, oncologists have relentlessly pursued the destruction of tumor cells by surgical, chemotherapeutic or radiation oncological means. Consistent with this focus, treatment plans are typically based on key characteristics of the tumor itself such as disease site, histology and staging based on local, regional and systemic dissemination. Precision medicine is similarly built on the premise that detailed knowledge of molecular alterations of tumor cells themselves enables better and more effective tumor cell destruction. Recently, host factors within the tumor microenvironment including the vasculature and immune systems have been recognized as modifiers of disease progression and are being targeted for therapeutic gain. In this review, we argue that-to optimize the impact of old and new treatment options-we need to take account of an epidemic that occurs independently of-but has major impact on-the development and treatment of malignant diseases. This is the rapidly increasing number of patients with excess weight and its' attendant metabolic consequences, commonly described as metabolic syndrome. It is well established that patients with altered metabolism manifesting as obesity, metabolic syndrome and chronic inflammation have an increased incidence of cancer. Here, we focus on evidence that these patients also respond differently to cancer therapy including radiation and provide a perspective how exercise, diet or pharmacological agents may be harnessed to improve therapeutic responses in this patient population.

Background: Radiation therapy (RT) can provide effective symptomatic palliation in patients with malignant pleural mesothelioma (MPM). Advances in RT technology, including intensity-modulated RT (IMRT) and volumetric-modulated arc therapy (VMAT), have improved treatment conformality, potentially improving the therapeutic ratio of RT. A novel 6-MV flattening-filter-free O-ring linear accelerator, Halcyon (TM) (Varian Medical Systems, Palo Alto, CA, USA), was built to provide such advanced therapies, while possibly reducing treatment time. Here, we report the initial clinical experience using HalcyonTM to deliver palliative RT for patients with MPM. Methods: We retrospectively assessed consecutive patients with MPM who received thoracic RT on Halcyon (TM). Their electronic medical records were reviewed for clinical, RT planning, treatment timing, and image-guidance RT (IGRT) data. Results: Four patients with metastatic MPM received palliative RT on HalcyonTM between 1/2017-1/2020 for severe pain (50%), dysphagia (25%), or dyspnea (25%). Targets included a combination of pleura, chest wall, lung, hilum, and mediastinum, with patient-specific dose and fractionation regimens ranging from 20-45 Gy in 5-15 fractions, and 75% of patients receiving concurrent systemic therapy. Pre-specified target and organ-at-risk constraints were met for nearly all plans. At a median follow-up of 2.2 months (range, 1.6-7.1 months), all patients experienced either improved (75%) or stable (25%) tumor-related symptoms following palliative RT. The mean 3D vector couch correction was 0.67 +/- 0.15 cm. The mean beam-on, treatment (beam-on plus cone-beam computed tomography times), and approximated total room usage times were 1.6 +/- 0.2, 1.8 +/- 0.2, and 9.8 +/- 0.2 min, respectively. Grade 2 fatigue and cough occurred in 25% and 25% of patients, and no patients experienced Grade >= 3 toxicity. Conclusions: In this initial clinical experience treating patients with palliative RT for MPM on Halcyon (TM), treatment provided symptom palliation and local control across multiple palliative scenarios, with minimal toxicity, acceptable dosimetry, and setup corrections and treatment times that compared favorably with other published experiences of MPM RT. Palliative RT on Halcyon (TM) can provide patients with MPM quick and safe tumor-related symptom relief, even in a frail, elderly population.