Rosai-Dorfman disease (RDD) is a rare, heterogeneous, non-Langerhans type histiocytosis. Local treatment can be recommended for symptomatic patients with unifocal or limited multifocal disease. Systemic treatments are used for patients with symptomatic extensive multifocal disease. Case reports describing radiation therapy for RDD standardly describe conventional dose fractionation schemes. Here we present a case of a woman with symptomatic subcutaneous RDD who was successfully treated with a hypofractionated radiation regimen.

Objectives: Spatially fractionated radiation therapy (SFRT) intentionally delivers a heterogeneous dose distribution characterized by alternating regions of high and low doses throughout a tumor. This modality may enhance response to subsequent whole tumor radiation in bulky and radioresistant lesions that are historically less responsive to conventional radiation doses alone. The current study presents a single institution experience with modern era SFRT using predominantly a volumetric modulated arc therapy (VMAT) lattice technique. Methods: Patients treated with SFRT between 10/2019 and 6/2022 were included for analysis. Patient characteristics, tumor characteristics, and dosimetric parameters were collected retrospectively as part of an institutional review board approved registry and protocol. Descriptive statistics were used to collate patient data and Kaplan Meier analysis were generated for overall survival and local control. Univariate analyses were used to investigate factors associated with outcomes. Results: A total of 176 patients with 186 sites treated were included. Median age was 64 and the most commonly treated histologies were non-small cell lung cancer and sarcoma. The most common SFRT dose was 20 Gy in 1 fraction with 88% of patients receiving follow-up whole tumor radiotherapy to a median EQD2 dose of 32.5 Gy (=10). Median gross tumor volume (GTV) was 480.5 cc (7.8-10,897.8). Median follow-up was 322 days with 1 year overall survival 37% and 1 year local control 81%. Local control was available in 138 treated sites (131 patients. SFRT factors including dose to 10% (D10%), dose to 90% (D90%), equivalent uniform dose, and mean dose were highly predictive of local control. Grade 3 toxicity occurred in 9 patients. All of these patients received follow-up whole tumor radiation and at least two of these were attributable to unexpected rapid regression of tumor. Conclusions: SFRT is a promising technique that appears to confer good local control across a disparate group of patients with bulky and radioresistant tumors. Dosimetric parameters of SFRT treatment plans may be independent predictors of local control. Further investigation is warranted as are prospective trials to evaluate the role of SFRT in both the palliative and definitive setting. (c) 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

e23554 Background: Follicular dendritic cell sarcoma (FDCS) is a low-grade neoplasm arising from follicular dendritic cells. Its diagnosis is challenging due to its extreme rarity, and the optimal management remains unknown. Methods: We conducted a retrospective study of FDCS patients (pts) seen at Mayo Clinic, MN since 2018. Time to event analyses were done from the time of diagnosis. Results: Ten pts with FDCS were identified (Table). The median age was 60 years (range, 38-76) and 5 were males. Abdominal pain was the most common presenting symptom (30%) followed by constitutional symptoms, shortness of breath, and vision change. In 3 pts, the diagnosis was incidental. The 2 most common primary locations were abdomen/pelvis (50%) and mediastinum (30%). Six pts (60%) presented with advanced disease and 3 (30%) had Castleman’s disease. Most (60%) had advanced disease. Six pts had Epstein-Barr virus in situ hybridization and all tested negative. Seven pts had next generation sequencing and 5 (83%) had genetic alterations detected with CDKN2A/B alterations being most frequent (3 pts, all with advanced disease). The median follow up was 4.3 years (range, 0.2-13.3). In the 4 patients with localized disease, 3 underwent complete surgical excision resulting in complete remissions (CRs). The one who received radiation had a partial remission (PR). The median time to progression after 1 st line treatment was 4 months (all with advanced disease). All 3 pts who died had advanced disease and 2 had CDKN2A/B alterations. Conclusions: In FDCS, localized diseases managed by surgical excision with or without radiation can achieve long term remissions. Advanced diseases generally do not respond to multimodality therapy including immunotherapy but can have disease stabilization with variable survival. CDKN2A/B mutations were common and potentially associated with a worse outcome. Better understanding of the impact of the FDCS mutational landscape on prognosis may provide novel approaches to therapy. [Table: see text]

Purpose: To assess any correlation between swallowing dysfunction and radiation dose to 5 subregions of the larynx. Methods and Materials: A cohort of 136 patients with head and neck cancer, treated with either photon or proton radiation therapy, was assessed using an endpoint of patient-reported swallowing scores, evaluated with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-H&N35 survey, within 1 month after treatment. Five subregions of the larynx were contoured, and dosimetric metrics were extracted for each subregion as well as the total larynx. Univariate and multivariate logistic regression statistical analyses were used to determine statistical correlation with the dose metrics and clinical variables. Univariate regression models were statistically compared using a non-nested model test. Results: Under univariate analysis, unilateral versus bilateral nodal irradiation (P = .004), concurrent chemotherapy (P = .007), and surgery (P = .015) were statistically significant predictors of poor swallowing score. Unilateral versus bilateral irradiation was statistically significant under multivariate analysis (P = .039). The epiglottis was the most predictive subregion of swallowing score, with a majority (21 of 25) of dosimetric variables being identified as statistically significant. The maximum dose to the epiglottis was the most significant dosimetric variable tested for poor swallowing score in both univariate (P = .003) and multivariate (P = .051) analyses. Comparison of univariate models indicated a general preference for epiglottic variables with the mean dose to the epiglottis being preferred at a statistically significant level in many cases. Conclusions: These results show the relatively increased sensitivity of the epiglottis compared with the rest of the larynx when considering patient-reported decrements in quality-of-life swallowing score and support both the inclusion of the epiglottis in standard larynx contours and the assessment of the epiglottis dose during plan evaluation. Our data suggest that keeping the mean and max doses to the epiglottis <20 to 37 Gy and <53 to 60 Gy, respectively, will reduce swallowing difficulties.

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.

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.

While much of the focus has shifted toward optimizing outcomes for the more favorable human papillomavirus (HPV)–associated head and neck squamous cell carcinomas (HNSCC), outcomes for HPV-negative HNSCCs have remained static for more than 2 decades. Concurrent systemic therapies beyond cisplatin have failed to deliver improved disease control, although the door remains open for emerging agents and adjuvant therapies. Riding a wave of noninferiority trials, radiation oncologists have adopted hypofractionation in a variety of other cancers.

Introduction: Immune checkpoint inhibitors (ICI) are an essential systemic therapy for advanced melanoma. However, most melanomas develop resistance to ICI. Tumor-derived soluble PD-L1 (sPD-L1) and other soluble immunosuppressive factors drive checkpoint inhibitor resistance and correlate with inferior survival. We previously showed that therapeutic plasma exchange (TPE) removes sPD-L1 from circulation. Thus, we hypothesized that TPE-mediated removal of sPD-L1 and other immunosuppressive factors could overcome immunotherapy resistance in refractory melanoma. Methods: In this clinical trial (NCT04581382), we prospectively enrolled eighteen (18) patients with widely metastatic melanoma with progression despite anti-PD-1 ICI and elevated sPD-L1 by ELISA (≥1.7ng/mL). Each patient received radiotherapy to between one and three metastatic lesions (at least two unirradiated lesions) followed by three TPE sessions on consecutive days and re-challenge with checkpoint inhibitor. The primary safety and efficacy endpoints of the study were adverse events (AEs) and sPD-L1 reduction by TPE, respectively. Secondary endpoints included RECIST-based response in unirradiated lesions and overall survival. Correlative studies included kinetics of sPD-L1 and soluble immonsuppressive factors and dynamics of peripheral immune cell phenotypes. Results: Mean age was 62 (SD 13) and seven of eighteen (39%) were female. Mean baseline sPD-L1 was 26.31 ng/mL (40.01). The treatment was well-tolerated with one (6%) patient with grade 3 and 4 adverse events from a central line infection after TPE. Levels of sPD-L1 were significantly reduced by TPE (mean 80.2% reduction, p<0.0001). Two patients (11.1%) experienced complete response (CR), one (5.6%) partial response, three (16.7%) stable disease, and 12 (66.7%) progressive disease. In one case, immunotherapy was discontinued after two years due to no detectable lesions. Changes in tumor-reactive (TTR) GZMB+/CX3CR1+/CD11ahigh and other peripheral immune cell populations predicted overall survival in this cohort. In addition to sPD-L1, other soluble mediators of ICI resistance were also reduced by TPE and predicted overall survival in this cohort. Summary/Conclusion: sPD-L1 and other soluble immunoregulatory signaling molecules are important mediators of ICI resistance. SBRT and TPE can resensitize ICI-refractory melanoma by removing these factors. Patients with persistently elevated or rapid rebound of sPD-L1 following TPE experienced poor response and overall survival. Serial monitoring of sPD-L1 may predict response to ICI and multiple courses of TPE may be necessary. Our findings may apply in other ICI-resistant cancers with elevated sPD-L1. ClinicalTrials.gov registration: NCT04581382, ReCIPE-M1 (Rescuing Cancer Immunotherapy with Plasma Exchange in Melanoma 1).

Granulomatous dermatitis is a common tissue reaction pattern seen in the skin or systematically in various presentations. Granulomatous dermatitis can be subclassified into infectious and non-infectious categories. This article focuses on a patient with non-infectious granulomatous dermatitis followed for many years. Past medical history included bilateral total shoulder arthroplasty complicated by prosthetic joint infections. In its early stages, the axillary rash was painful and had many fluid-filled blisters. Ultimately, the histology of the rash deemed the lesion non-infectious and mostly due to an inflammatory process. Specifically, ionizing radiation was used for this patient. The category of granulomatous processes is broad and there are many subtypes. Other treatment options for non-infectious granulomatous processes may include corticosteroids, phototherapy, and interferon-gamma injections. The differential for granulomatous processes is extensive and treatment should be decided on a case-by-case basis.

Leonine facies (LF), characterized by lion-like appearance with prominent furrows, can arise from a variety of conditions including cutaneous T-cell lymphoma (CTCL) / mycosis fungoides (MF). It is an uncommon and aggressive manifestation of CTCL, generally associated with a poor prognosis and other high risk features of disease including blood involvement [1]. While it can occur at the initial diagnosis, it is most commonly encountered as a manifestation of progression after previous therapies. No standard therapy exists specifically for CTCL with LF and treatment is individualized. Complete remission is rare and survival after diagnosis is quite limited. Herein we report our experience using intensity modulated proton therapy (IMPT) as a salvage strategy for a patient with stage IVA CTCL and LF and discuss the unique rationale for considering proton therapy for this uncommon circumstance.

Introduction: Outcomes from multidisciplinary lymphoma tumor boards in the molecular era are limited, and the effects of transitioning to virtual formats during the COVID-19 pandemic are not well-documented. This study evaluates how the transition of the Mayo Clinic Lymphoma Tumor Board to a virtual format has impacted its effectiveness and operations. The board, part of the International Mayo Clinic Care Network (MCCN), involves case presentations, subspecialist reviews, and collaborative recommendations. Methods: The Mayo Clinic Lymphoma Tumor Board, an integral part of the Mayo Clinic Care Network (MCCN), conducted a comprehensive review of lymphoma cases from 2014 to 2024. The board's review process involves a structured approach including the presentation of clinical case details, radiology and hematopathology findings, proposed treatment options, relevant literature review, and discussions. From 2014 to 2024, the Mayo Clinic Lymphoma Tumor Board reviewed a total of 722 patients. The review process involves a multidisciplinary team, including physicians, pharmacists, clinical research associates, and trainees. Recommendations and changes related to radiology interpretation, pathologic diagnosis, and treatment approaches were documented and tracked prospectively. In March 2020, the board transitioned to a virtual format due to the COVID-19 pandemic. This shift allowed for remote participation and continued collaborative review while maintaining the board's structured approach and documentation practices. Results: In a total of 722 patients, changes in care were identified in 423 patients, including 287 with newly diagnosed lymphoma and 136 with relapse or refractory disease. Among those who experienced changes, 94 had diffuse large B-cell lymphoma, 49 had follicular lymphoma, 39 had marginal zone lymphoma, 36 had classical Hodgkin lymphoma, and 29 had mantle cell lymphoma. Prior to the COVID-19 pandemic, 431 patients were analyzed, with 217 (50.3%) experiencing changes. A total of 268 changes were documented among these patients. Changes in radiologic interpretation occurred in 9 patients (2.1% of 431 total patients). Pathologic diagnosis changes were noted in 42 patients (9.7%). Additional testing was recommended for 73 patients (16.9%), and clinical management was altered for 144 patients (33.4%). After transitioning to a virtual format, 291 patients were reviewed post-COVID, with 206 (70.8%) having recommended changes. The total number of change recommendations was 322, reflecting increases across all components compared to previous data, with adjustments for varying numbers of patients reviewed. Specifically, radiologic interpretation changes occurred in 21 patients (7.2%), pathologic diagnosis changes in 57 patients (19.6%), additional testing recommendations for 85 patients (29.2%), and clinical management alterations in 159 patients (54.7%). Conclusion: Transitioning to a virtual format in the Mayo Clinic Lymphoma Tumor Board's continued to demonstrate the effectiveness, with increased changes in diagnostic interpretations and clinical management. These results illustrate the potential of virtual tumor boards to improve collaborative decision-making and adapt to evolving clinical needs.

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 de fining the role of local therapies in combination with ICIs. We identi fied 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 identi fied; 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.

PURPOSE:H. pylori eradication therapy (HPE) can lead to tumor regression in H. pylori-positive (HPP) gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, some patients do not have detectable H. pylori (HP) infection (H. pylori-negative [HPN]) and the guidelines differ in their initial approach to HPN patients. The National Comprehensive Cancer Network (NCCN) recommends proceeding to radiation therapy, whereas European Society for Medical Oncology suggests HPE for every patient, even those who are HPN. To address this issue, we evaluated the effectiveness of HPE in limited-stage gastric MALT lymphoma. MATERIALS AND METHODS:We retrospectively reviewed patients newly diagnosed with stage IE gastric MALT lymphoma between January 2002 and December 2022. The primary outcome was the complete remission (CR) rate defined as no macroscopic findings of lymphoma and negative gastric biopsy at the follow-up gastric endoscopy. RESULTS:Fifty-two patients were reviewed, and HP infection was detected in 19 (36.5%) patients-14 by immunostaining, three by serology, and one each by stool antigen and urea breath test. All 19 HPP and eight of the 33 HPN patients received HPE treatment. The CR rate was 63% (12/19) in HPP patients and 13% (1/8) in HPN patients (P = .033). After a median follow-up of 89.7 months, only two of the 12 HPP patients achieving CR have relapsed; the one HPN patient who received HPE remains in CR at 12+ months. CONCLUSION:For limited-stage HPP gastric MALT lymphoma, HPE is an effective and durable first-line treatment and should be used. For HPN patients, the CR rate with HPE is very low in our experience and is thus in support of the NCCN guideline.

Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing integral dose and reducing acute and late toxicities, such as dysgeusia, feeding tube dependence, xerostomia, secondary malignancies, and neurocognitive dysfunction. Despite its benefits in dose distribution and biological effectiveness, the application of proton therapy is challenged by uncertainties in its relative biological effectiveness (RBE). Overcoming the challenges related to RBE is key to fully realizing proton therapy’s potential, which extends beyond its physical dosimetric properties when compared with photon-based therapies. In this paper, we discuss the clinical significance of RBE within treatment volumes and adjacent serial organs at risk in the management of head and neck and skull-base tumors. We review proton RBE uncertainties and its modeling and explore clinical outcomes. Additionally, we highlight technological advancements and innovations in plan optimization and treatment delivery, including linear energy transfer/RBE optimizations and the development of spot-scanning proton arc therapy. These advancements show promise in harnessing the full capabilities of proton therapy from an academic standpoint, further technological innovations and clinical outcome studies, however, are needed for their integration into routine clinical practice.

OBJECTIVES:Social determinants of health (SDOH) can influence access to cancer care, clinical trials, and oncologic outcomes. We investigated the association between SDOH, distance from treatment center, and treatment type with outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] patients treated at a tertiary care center. STUDY DESIGN:Retrospective review. METHODS:HPV(+)OPSCC patients treated surgically from 2006 to 2021 were selected from our departmental Oropharyngeal Cancer RedCap database. Demographic data, treatment, and oncologic outcomes were extracted. Distance was calculated in miles between the centroid of each patient zip code and our hospital zip code (zipdistance). RESULTS:874 patients (89 % male; mean age: 58 years) were identified. Most patients (96 %) reported Non-Hispanic White as their primary race. 204 patients (23 %) had a high-school degree or less, 217 patients (25 %) reported some college education or a 2-year degree, 153 patients (18 %) completed a four-year college degree, and 155 patients (18 %) had post-graduate degrees. Relative to those with a high-school degree, patients with higher levels of education were more likely to live further away from our institution (p < 0.0001). Patients who received adjuvant radiation therapy elsewhere lived, on average, 104 miles further away than patients receiving radiation at our institution (Estimate 104.3, 95 % CI 14.2-194.4, p-value = 0.02). In univariable Cox PH models, oncologic outcomes did not significantly differ by zipdistance. CONCLUSIONS:Education level-and access to resources-varied proportionally to a patient's distance from our center. Patients travelling further distances for surgical management of OPSCC were more likely to pursue adjuvant radiation therapy at an outside institution. Distance traveled was not associated with oncologic outcomes. Breaking down barriers to currently excluded populations may improve access to clinical trials and improve oncologic outcomes for diverse patient populations.

ObjectivesTo investigate the relationship between nutritional supplementation and radiation dose to the pharyngeal constrictor muscles and larynx for head and neck (HN) cancer patients undergoing radiotherapy.MethodsWe retrospectively analyzed radiotherapy (RT) dose for 231 HN cancer patients, focusing on the pharyngeal constrictors and larynx. We defined nutritional supplementation as feeding tube utilization or >10% weight loss from baseline within 90 days after radiotherapy completion. Using deformable image registration (DIR), we mapped each patient’s anatomical structures to a reference coordinate system, and corresponding deformations were applied to dose matrices. Voxel doses were utilized as features for ridge logistic regression models, optimized through 5-fold cross-validation. Model performance was assessed with area under the curve of a receiver operating curve (AUC) and F1 score. We built and compared models using 1) pharyngeal constrictor voxels, 2) larynx voxels, 3) clinical factors and mean regional dose metrics, and 4) clinical factors and dose-volume histogram metrics. Test set AUCs were compared among the models, and feature importance was evaluated.ResultsDIR of the pharyngeal constrictors and larynx yielded mean Dice coefficients of 0.80 and 0.84, respectively. Pharyngeal constrictors voxels and larynx voxel models had AUC of 0.88 and 0.82, respectively. Voxel-based dose modeling identified the superior to middle regions of the pharyngeal constrictors and the superior region of larynx as most predictive of feeding tube use/weight loss. Univariate analysis found treatment setting, treatment laterality, chemotherapy, baseline dysphagia, weight, and socioeconomic status predictive of outcome. An aggregated model using mean doses of pharyngeal constrictors and larynx subregions had an AUC of 0.87 and the model using conventional DVH metrics had an AUC of 0.85 with p-value of 0.04. Feature importance calculations from the regional dose model indicated that mean doses to the superior-middle pharyngeal constrictor muscles followed by mean dose to the superior larynx were most predictive of nutritional supplementation.ConclusionsMachine learning modeling of voxel-level doses enables identification of subregions within organs that correlate with toxicity. For HN radiotherapy, doses to the superior-middle pharyngeal constrictors are most predictive of feeding tube use/weight loss followed by the doses to superior portion of the larynx.

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.

PURPOSE:Minibeam radiation therapy (MBRT) is characterized by the delivery of submillimeter-wide regions of high "peak" and low "valley" doses throughout a tumor. Preclinical studies have long shown the promise of this technique, and we report here the first clinical implementation of MBRT. METHODS AND MATERIALS:A clinical orthovoltage unit was commissioned for MBRT patient treatments using 3-, 4-, 5-, 8-, and 10-cm diameter cones. The 180 kVp output was spatially separated into minibeams using a tungsten collimator with 0.5 mm wide slits spaced 1.1 mm on center. Percentage depth dose (PDD) measurements were obtained using film dosimetry and plastic water for both peak and valley doses. PDDs were measured on the central axis for offsets of 0, 0.5, and 1 cm. The peak-to-valley ratio was calculated at each depth for all cones and offsets. To mitigate the effects of patient motion on delivered dose, patient-specific 3-dimensional-printed collimator holders were created. These conformed to the unique anatomy of each patient and affixed the tungsten collimator directly to the body. Two patients were treated with MBRT; both received 2 fractions. RESULTS:Peak PDDs decreased gradually with depth. Valley PDDs initially increased slightly with depth, then decreased gradually beyond 2 cm. The peak-to-valley ratios were highest at the surface for smaller cone sizes and offsets. In vivo film dosimetry confirmed a distinct delineation of peak and valley doses in both patients treated with MBRT with no dose blurring. Both patients experienced prompt improvement in symptoms and tumor response. CONCLUSIONS:We report commissioning results, treatment processes, and the first 2 patients treated with MBRT using a clinical orthovoltage unit. While demonstrating the feasibility of this approach is a crucial first step toward wider translation, clinical trials are needed to further establish safety and efficacy.