Outcomes of r/r B-cell NHL patients with limited (<5 Sites) pre-CART Disease Bridged With or Without Radiotherapy.

Unirradiated relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL) patients who undergo anti-CD19 Chimeric Antigen Receptor T-cell Therapy (CART) have a predominant localized pattern of relapse, the significance of which is heightened in individuals with limited/localized pre-CART disease. This study reports on the outcomes of r/r NHL patients with limited (<5 involved sites) disease bridged with or without radiotherapy (BRT). A multi-center retrospective review of 150 patients with r/r NHL who received CART with <5 disease sites prior to leukapheresis was performed. Bridging treatment, if any, was administered between leukapheresis and CART infusion. Study endpoints included relapse free-survival (RFS), event-free survival (EFS) and overall survival (OS). Prior to CART infusion, 48 (32%) patients received BRT and 102 (68%) did not. The median follow-up was 21 months. Following CART infusion, BRT patients had higher objective response (92% vs 78%, p=0.046) and sustained complete response (54% vs 33%, p=0.015) rates. Local relapse in sites present prior to CART was lower in the BRT group (21% vs. 46%, p=0.003). BRT patients had improved 2-year RFS (53% vs 44%, p=0.023) and 2-year EFS (37% vs 34%, p=0.039) compared to no BRT patients. The impact of BRT was most prominent in patients who had ≤2 pre-CART involved disease sites, with 2-year RFS of 62% in patients who received BRT compared to 42% in those who did not (p=0.002). BRT prior to CART for patients with limited (<5 involved disease sites) r/r NHL improves response rate, local control, RFS, and EFS without causing significant toxicities.

Fine-Tuning Low-Dose Total Skin Electron Therapy for Optimal Management of Cutaneous T-Cell Lymphoma: A Comparative Analysis of Regimens.

Purpose: Low-dose total skin electron beam therapy (TSEBT) is a proven treatment for managing cutaneous T-cell lymphoma (CTCL) and Sezary syndrome with skin burden. We performed a retrospective comparison of response rates and time to progression for patients receiving low-dose TSEBT based on dose per fractionation, total dose, and stage. Methods and Materials: One hundred and ten patients with CTCL and Sezary syndrome were treated with 135 courses of low-dose (400-1500 cGy) TSEBT or subtotal skin electron therapy at multiple centers of a single institution between August 2003 and June 2023. Patients were stratified according to total dose, dose per fraction, and stage. Results: The median follow-up was 301 days (IQR, 141, 767). The median age at treatment was 69.9 years (range, 29.7-96.5). T-stage distribution was as follows: 3 (2.7%) T1, 74 (67.3%) T2, 16 (14.5%) T3, and 17 (15.5%) T4. American Joint Committee on Cancer eighth edition stage distribution was as follows: 3 (2.7%) IA, 53 (48.2%) IB, 3 (2.7%) IIA, 16 (14.5%) IIB, 8 (7.3%) IIIA, 19 (17.3%) IVA, and 8 (7.3%) IVB. There was no significant difference in disease distribution between patients treated with different fractionation schemes. The overall response rate was 89.6%. Forty-four courses (32.6%), 34 courses (25.2%), and 43 (31.9%) resulted in a complete, near-complete, and partial response, respectively. Fourteen courses (10.4%) resulted in no clinical response. For all patients, the median time to response was 43.0 days (IQR, 23.0-70). The median time to skin progression for all patients was 107.5 days (IQR, 67.8-233.5). Conclusions: This analysis demonstrated that CTCL patients treated with low-dose radiation therapy delivered over various fractionation schemes had similar overall response rates and median time to progression.

Contemporary radiation therapy use in Hodgkin lymphoma.

Radiation therapy assumes a pivotal role in Hodgkin lymphoma management, especially within combined modality therapy. It serves as a cornerstone in early-stage disease and in mitigating high-risk instances of local relapse in advanced stages. Over recent decades, radiation therapy has undergone significant advancements, notably alongside diagnostic imaging improvements, facilitating the reduction of radiation field size and dosage. This progress has notably led to minimized toxicity while upholding treatment efficacy. This comprehensive review extensively evaluates the indications and advancements in radiation therapy for Hodgkin lymphoma, with a primary focus on enhancing treatment efficacy while minimizing radiation-related toxicities. The exploration encompasses a detailed examination of various radiation fields, techniques and delivery modalities employed in Hodgkin lymphoma treatment, including intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and proton therapy. It delves into the intricacies of optimal dose selection and treatment planning strategies aimed at achieving maximal disease control while concurrently minimizing the risk of long-term side effects.

Tailoring Radiation Therapy for Patients With Limited Cutaneous T Cell Lymphoma: Preliminary Clinical Experience With Subtotal Skin Electron Therapy.

BACKGROUND/AIM: Total skin electron beam therapy (TSEBT) is an effective treatment for managing cutaneous T-cell lymphoma (CTCL), but may result in unnecessary toxicity. With the production of a custom rolling shield holding a configurable stack of plastic slats to block uninvolved skin, we implemented a program for subtotal skin electron beam therapy (STSEBT). We report our preliminary experience with STSEBT vs. TSEBT to manage CTCL. PATIENTS AND METHODS: A retrospective review of 32 CTCL patients who were treated at a single institution between February 28th, 2017, and May 25th, 2022, was completed. Of these cases, seven patients received STSEBT and 25 received TSEBT. RESULTS: Thirty-two patients underwent a course of STSEBT or TSEBT. The median follow-up was 465 days and the median age at diagnosis was 70.8 years. Stage distribution was as follows: one (3%) IA, 16 (50%) IB, 6 (19%) IIB, two (6%) IIIA, five (16%) IVA, and two (6%) IVB. The overall response rate was 96%. For patients receiving TSEBT (n=25), three (12%), 10 (40%), and 11 (44%) had a CR, NCR, and PR, respectively. For the patients receiving STSEBT, four (57.1%), three (42.9%), and zero (0%) had a CR, NCR, and PR, respectively. There was one patient (4%) with no response. Cumulative incidence of progressive skin disease requiring additional electron therapy at three months was 21.1% [IQR=8.6, 51.5%], 36.8% [IQR=20, 68%] at six months, and 57.9% [IQR=38.5, 87.1%] at one year. Low rates of toxicities were recorded. CONCLUSION: This analysis demonstrated that treatment of CTCL patients with low disease burden with STSEBT results in similar overall response and time to progression compared to treatment with TSEBT.

International Prognostic Score for Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

PURPOSE: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. METHODS: Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation. RESULTS: We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41). CONCLUSION: In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).

Prompt Pain Relief From Bone Metastases: The Virtual Simulation Program.

Purpose: Rapid pain relief for patients with bone metastases can be a challenge due to the lengthy and complex radiation therapy workflow. The purpose of this study was to evaluate the time (in days) between initial radiation oncology consultation and start of palliative radiation treatment after implementing an alternative virtual simulation palliative workflow. Methods and Materials: Patients meeting strict criteria were selected for virtual simulation, which included only those with painful bone metastases who were recommended palliative radiation therapy using standard anterior-posterior/posterior-anterior or opposed lateral fields. A recent (within 30 days) diagnostic computed tomography (CT) scan clearly visualizing the target volume was required for treatment planning. For comparison, a reference group of 40 consecutive patients with bone metastases who underwent in-person CT simulation before virtual simulation implementation was reviewed. Results: Forty-five patients were treated for painful bone metastases as part of the virtual simulation program from May 2021 to October 2022. Regarding travel distance, 23 patients lived locally (<50 miles from the treatment center) and 22 patients were distant (≥50 miles from the treatment center). Average time from consultation to treatment for all patients undergoing virtual simulation was 3.7 days, compared with 7.5 days for patients undergoing in-person CT simulation (3.8 days sooner, on average; P ≤ .001). Before full implementation of the virtual simulation program, 5 eligible patients participated in a virtual simulation pilot from April 2021 to May 2021, in which each patient was contoured and planned on both a pre-existing diagnostic CT scan and a standard CT simulation scan. For virtual simulation-based plans, the average V90, V95, and V99 were 99.99%, 99.87%, and 96.70%. No significant planning target volume (PTV) coverage difference was found on subsequent in-person CT simulation scans. Conclusions: The virtual simulation program decreased the time from consultation to start of treatment by more than 50% for patients recommended palliative radiation therapy for painful bone metastases. This benefit was most significant for outpatients traveling ≥50 miles for treatment. Virtual simulation-based planning can be considered for patients anxious to proceed with radiation therapy quickly or in underserved settings with limited transportation options to regional treatment centers.

Patterns of progression after immune checkpoint inhibitors for Hodgkin lymphoma: implications for radiation therapy.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have demonstrated remarkable response rates in relapsed or refractory Hodgkin lymphoma (HL). Still, most patients eventually progress. Patterns of progression after ICIs are not well described and are essential to defining the role of local therapies in combination with ICIs. We identified patients who received ICIs for HL between 2013 and 2022. Fludeoxyglucose-18 positron emission tomography (FDG-PET) before initiating ICI and at progression on/after ICI were reviewed, and areas of active HL were recorded. An exploratory analysis of treatable progression included patients with ≤5 sites of disease on pre-ICI FDG-PET and progression only at pre-ICI sites. Ninety patients were identified; 69 had complete records, and of these, 32 (52%) had relapsed at ICI initiation, 17 (25%) were refractory, and 16 (23%) received ICI as first-line therapy. Forty-five of 69 patients had ≤5 sites of disease (limited) on pre-ICI FDG-PET. Patients with >5 sites of disease had a higher risk of progression, and every site of disease >5 sites conferred an additional 1.2x higher chance of progression. At a median follow-up of 4.0 years, 41 of 69 patients had progressed on/after ICIs (cumulative incidence 66.4%), and of these, 22 of 41 patients progressed only at pre-ICI sites (cumulative incidence 39.4%). In an exploratory analysis, the cumulative incidence of a treatable progression among 45 patients with limited disease was 34%. The cumulative incidence of any progression among this cohort was 58.9%. More than one-third of patients with limited disease before ICIs experienced progression only at pre-ICI sites of disease. These patients could be candidates for radiation during or after ICIs.

The Next Chapter in Immunotherapy and Radiation Combination Therapy: Cancer-Specific Perspectives.

Immunotherapeutic agents have revolutionized cancer treatment over the past decade. However, most patients fail to respond to immunotherapy alone. A growing body of preclinical studies highlights the potential for synergy between radiation therapy and immunotherapy, but the outcomes of clinical studies have been mixed. This review summarizes the current state of immunotherapy and radiation combination therapy across cancers, highlighting existing challenges and promising areas for future investigation.

Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases

Chronic Schistosoma mansoni infection leads to a type 2-immune response with increased production of interleukin (IL-10). Evidence indicates chronic exposure to S. mansoni down regulates the type 1 immune response and prevents the onset of Th1-mediated diseases such as multiple sclerosis, diabetes mellitus and Cronh's disease. Furthermore, our own studies have revealed that chronic exposure to S. mansoni also down regulates atopic disease, Th2-mediated diseases. Our studies show an inverse association between the skin prick test reactivity and infection with S. mansoni and show the severity of asthma is reduced in subjects living in an endemic area of S. mansoni. Moreover, we hypothesize the mechanisms involved in the modulation of inflammatory response in atopic individuals, is likely dependent on IL-10 production, an anti-inflammatory cytokine elevated during helminth infections. Patients with asthma and helminth infections produced less IL-5 than patients with asthma without helminth infections, and this down regulation could, in part, be mediated by IL-10. In conclusion, helminthic infections, through induction of regulatory mechanisms, such as IL-10 production, are able to modulate the inflammatory immune response involved in the pathology of auto-immune and allergic disease.