Low-Dose Hypofractionated Total Skin Electron Beam Therapy for Adult Cutaneous T-Cell Lymphoma

PurposeHistorically, the standard of care for total skin electron beam therapy (TSEBT) delivered 30 to 36 Gy over 5 to 10 weeks. Given the high risk of relapse, a majority of patients require additional treatments. Therefore, attempts to use a shortened course of TSEBT have been investigated.Methods and MaterialsWe conducted a single-institution retrospective review to evaluate disease response, control, and toxicity using a low-dose, hypofractionated course of TSEBT (HTSEBT) in patients with mycosis fungoides.ResultsForty patients received 57 courses of HTSEBT. Median dose (Gy)/fractionation was 12/3, spanning a median time of 2.4 weeks. Overall response rate of patients assessed (n = 54) was 100%. Thirty-one courses (57.4%) resulted in a complete response and 23 courses (42.6%) resulted in a partial response. Cumulative incidence of progressive skin disease at 3 months was 37.2%, at 6 months, 56.9%, and at 1 year, 81.5%. Of the 40 patients treated with a first course of HTSEBT, 31 received subsequent courses of radiotherapy. Cumulative incidence of subsequent treatment was 28.0% at 3 months, 46.8% at 6 months, and 70.0% at 1 year. Patients who underwent repeat courses of HTSEBT continued to have similar treatment responses to repeat courses without increased toxicities. Toxicities from all courses were acceptable with the exception of 1 patient, who experienced grade 4 skin toxicity (moist desquamation requiring hospitalization).ConclusionsLow-dose HTSEBT provides good palliation in patients with cutaneous T-cell lymphoma with a satisfactory response and toxicity profile. HTSEBT allows therapy to be completed in far fewer treatments. Low-dose HTSEBT is an appropriate treatment option for patients unable to come for daily treatment. HTSEBT provides a way to decrease exposure to other patients and staff during public health emergencies such as the coronavirus disease 2019 (COVID-19) pandemic.     

Maintenance Therapy for Cutaneous T-cell Lymphoma After Total Skin Electron Irradiation: Evidence for Improved Overall Survival With Ultraviolet Therapy

BackgroundTreatment of cutaneous T-cell lymphoma (CTCL) with total skin electron beam (TSEB) therapy has been associated with deep responses but short progression-free intervals. Maintenance therapy might prolong the response duration; however, limited data assessing the outcomes with maintenance therapy after TSEB are available. We evaluated the effect of maintenance therapy on the outcomes for patients with CTCL receiving TSEB therapy.Materials and MethodsWe conducted a single-center retrospective analysis of 101 patients with CTCL who had received TSEB therapy from 1998 to 2018 at the Winship Cancer Institute of Emory University and compared the overall survival (OS) and progression-free survival (PFS) for patients had received maintenance therapy, including retinoids, interferon, ultraviolet therapy, nitrogen mustard, and extracorporeal photopheresis compared with those who had not.ResultsWe found that pooled maintenance therapies improved PFS (hazard ratio [HR], 0.60; P = .026) but not OS (median HR, 0.73; P = .264). The median PFS and OS was 7.2 months versus 9.6 months and 2.4 years versus 4.2 years for the no maintenance and maintenance groups, respectively. On exploratory analysis of the individual regimens, ultraviolet therapy was associated with improved OS (HR, 0.21; P = .034) and PFS (HR, 0.26; P = .002) compared with no maintenance.ConclusionAmong the patients with CTCL who had received TSEB therapy, maintenance therapy improved PFS for all patients, and ultraviolet-based maintenance improved both PFS and OS in a subset of patients.     

Temozolomide as a Single Agent Maintenance Therapy in Elderly Patients With Primary CNS Lymphoma

IntroductionOptimal management of elderly patients with primary central nervous system lymphoma (PCNSL) after induction therapy is unclear. Whole-brain radiotherapy and autologous stem cell transplantation carry increased toxicity in patients older than 60 years of age, which might outweigh the benefits in this group. Temozolomide (TMZ) has established antineoplastic activity in the central nervous system in other disease states, with a favorable toxicity profile.Patients and MethodsWe report efficacy and tolerability in a series of 10 patients treated off-label with TMZ maintenance after completion of R-MPV (rituximab, methotrexate, procarbazine and vincristine) treatment for or primary diagnosed PCNSL.ResultsMedian progression-free survival (PFS) was 57 months, 2-year PFS was 67%, and 5-year PFS was 33%. Median overall survival (OS) was 63 months, 2-year OS was 88%, and 5-year OS was 57%. TMZ was generally well tolerated, with the most common toxicity of Grade 3 or higher being thrombocytopenia in 3 patients (30%).ConclusionThese outcomes suggest that TMZ might have activity for maintenance in elderly patients with PCNSL, when more aggressive treatments are contraindicated.     

Risk-Stratified Intraoperative Radiation Therapy as a Definitive Adjuvant Radiation Therapy Modality for Women With Early Breast Cancer

Radiation therapy is an integral component of adjuvant therapy in women who undergo breast conservative surgery, decreasing the likelihood of tumor recurrence and extending survival. The likelihood of tumor recurrence is highest within a proximity of the lumpectomy cavity, which prompted the idea of partial breast irradiation in place of the usual standard-of-care treatment with external beam whole breast radiation therapy. Targeted intraoperative radiation therapy (TARGIT-A) is a multicenter trial initially developed in 1999 and designed as a randomized clinical trial comparing whole breast radiation therapy to risk-adapted intraoperative radiation therapy (IORT). TARGIT-A recruited its first patient in March 2000, with the study concluding in 2012. At a median follow-up of 8.6 years, the prepathology TARGIT-A trial noted results to be noninferior to external beam radiation therapy, with no statistically significant difference in ipsilateral breast tumor recurrence, mastectomy-free survival, distant disease-free survival, or breast cancer–specific mortality. These results are consistent with the majority of retrospective and prospective trials. Risk-adapted IORT, as performed in the prospective randomized TARGIT-A trial, gives level 1 evidence that this approach is a standard option in the treatment of breast cancer.     

Pneumothorax as a Complication of Radiation Therapy for Primary Lung Cancer

A case of spontaneous pneumothorax complicating irradiation for bronchogenic carcinoma is presented. Pneumothorax developed in a collapsed lung caused by a central bronchogenic carcinoma. The cause is presumably secondary to either a bronchopleural fistula by tumour or sudden expansion of the lung following irradiation. Various tumours of the lung have been associated with spontaneous pneumothorax, including metastatic osteogenic sarcoma¹², eosinophilic granuloma⁴, teratoma¹¹, other metastatic sarcomas³, lymphoma following radiation therapy⁸, and primary bronchogenic carcinomas^{1,2,3,5,6,7,9,10}. We have encountered a case of spontaneous pneumothorax complicating irradiation for bronchogenic carcinoma. To our knowledge, this is the first report in the English radiologic literature, and the second, in the English literature, of a case of spontaneous pneumothorax following radiation therapy for proven bronchogenic carcinoma.     

Salvage Therapy for Relapsed Mediastinal B-Cell Lymphoma with Allogeneic HLA-Identical Related Donor Bone Marrow Transplantation, Donor Lymphocyte Infusion and IDEC-C2B8

Primary B-cell lymphoma of the mediastinum is an aggressive non-Hodgkin's lymphoma with distinct clinicopathologic features. Response rates are between 60-80% following intensive chemotherapy regimens. Poor responders or patients with an early relapse usually do not achieve a prolonged second remission with conventional salvage therapy protocols and therefore qualify for intensive or experimental approaches. Here we describe two patients of same age, gender and stage with primary mediastinal B-cell lymphoma and an early relapse after the first courses of combination chemotherapy and irradiation of the mediastinum. One patient relapsed after a salvage therapy with allogeneic donor-related bone marrow transplantation and donor lymphocyte infusion but responded again with a continuing good partial remission after infusion of the chimeric anti-CD20 antibody IDEC-C2B8. For the other patient an allogeneic bone marrow transplantation was not possible. He finally failed to respond to salvage therapy with IDEC-C2B8 and died of progressive disease. The anti-CD20 antibody IDEC-C2B8 induced a partial remission in a patient with primary mediastinal B-cell lymphoma refractory to other therapeutic approaches, including allogeneic bone marrow transplanatation (alloBMT), donor lymphocyte infusion (DLI) and irradiation. The role of IDEC-C2B8 as a component of salvage regimens appears to be worthy for further evaluation in high-risk patients with primary mediastinal B-cell lymphoma     

Tumor bulk as a prognostic factor for the management of localized aggressive non-Hodgkin's lymphoma: a survey of the Japan Lymphoma Radiation Therapy Group

PURPOSE: To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL). METHODS AND MATERIALS: The survey was carried out at 25 radiation oncology institutions in Japan in 1998. The 5-year event-free (EFS) and overall survival rates (OAS) were calculated, and univariate and multivariate analyses were done to identify which of the following factors, namely, gender, age, performance status (PS), serum lactate dehydrogenase (LDH) level, Stage (I vs. II), tumor bulk (maximum diameter), and treatment, were significant from the viewpoint of prognosis. RESULTS: A total of 1141 patients with Stage I and II NHL were treated by the Japanese Lymphoma Radiation Therapy Group between 1988 and 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate- and high-grade lymphomas in working formulation, constituted the core of this study. Primary tumors arose mainly from extranodal organs (71%) in the head and neck (Waldeyer's ring: 36% and sinonasal cavities: 9%). The factors associated with poorer prognosis were age over 60 years old (p < 0. 0001), radiation therapy alone (p < 0.0001), PS = 2-4 (p = 0.0011), (sex male, p = 0.0078), a bulky tumor more than 6 cm in maximum diameter (p = 0.0088), elevated LDH (p = 0.0117), and stage II (p = 0.0642). A median dose of 42 Gy was delivered mainly to the involved fields. Short-course chemotherapy was provided in 549 (70%) patients. The 5-year OAS and EFS rates for all patients were 71% and 67%, respectively. According to the stage-modified International Prognostic Index, the 5-year EFS of the patients with risk factors from 0 to 1 was 76%, 61% for patients with two risk factors, and 26% for patients with three or more risk factors. CONCLUSION: Extranodal presentation, especially Waldeyer's ring and sinonasal cavities, is encountered more frequently in Japan than in Western countries. Tumor bulk is an important prognostic factor in patients with localized aggressive extranodal NHL. Short course chemotherapy followed by radiation therapy was associated with prolonged survival in patients with localized aggressive NHLs of extranodal origin and 0-1 risk factor.