Salvage of patients with relapsed and refractory Hodgkin disease (HD) with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dose-dense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P < .001). These results compare favorably with other series and document the feasibility and efficacy of giving uniform dose-dense and dose-intense cytoreductive chemotherapy and integrating accelerated fractionation radiotherapy into an ASCT treatment program. This prognostic model provides a basis for risk-adapted HDT.

Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL). Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL), consolidation after systemic therapy, salvage treatment, or palliation. The wide range of presentations of ENL, involving any organ in the body and the spectrum of histological sub-types, poses a challenge both for routine clinical care and for the conduct of prospective and retrospective studies. This has led to uncertainty and lack of consistency in RT approaches between centers and clinicians. Thus far there is a lack of guidelines for the use of RT in the management of ENL. This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL, and to address the technical challenges of simulation, volume definition and treatment planning for the most frequently involved organs. Specifically, detailed recommendations for RT volumes are provided. We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL. We have adopted RT volume definitions based on the International Commission on Radiation Units and Measurements (ICRU), as has been widely adopted by the field of radiation oncology for solid tumors. Organ-specific recommendations take into account histological subtype, anatomy, the treatment intent, and other treatment modalities that may be have been used before RT.

PURPOSE: We conducted a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) as second-line therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) (ClinicalTrials.gov identifier: NCT03618550 ). METHODS: Transplant eligible patients with rel/ref cHL following first-line therapy were treated with two to four cycles of pembrolizumab (200 mg intravenous [IV], day 1), gemcitabine (1,000 mg/m² IV, days 1 and 8), vinorelbine (20 mg/m² IV, days 1 and 8), and liposomal doxorubicin (15 mg/m², days 1 and 8), given on 21-day cycles. The primary end point was complete response (CR) following up to four cycles of pembro-GVD. Patients who achieved CR by labeled fluorodeoxyglucose-positron emission tomography (Deauville ≤ 3) after two or four cycles proceeded to high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). HDT/AHCT was carried out according to institutional standards, and brentuximab vedotin maintenance was allowed following HDT/AHCT. RESULTS: Of 39 patients enrolled, 41% had primary ref disease and 38% relapsed within 1 year of frontline treatment. 31 patients received two cycles of pembro-GVD, and eight received four cycles. Most adverse events were grade 1 or two, whereas few were grade 3 and included transaminitis (n = 4), neutropenia (n = 4), mucositis (n = 2), thyroiditis (n = 1), and rash (n = 1). Of 38 evaluable patients, overall and CR rates after pembro-GVD were 100% and 95%, respectively. Thirty-six (95%) patients proceeded to HDT/AHCT, two received pre-HDT/AHCT involved site radiation, and 13 (33%) received post-HDT/AHCT brentuximab vedotin maintenance. All 36 transplanted patients are in remission at a median post-transplant follow-up of 13.5 months (range: 2.66-27.06 months). CONCLUSION: Second-line therapy with pembro-GVD is a highly effective and well-tolerated regimen that can efficiently bridge patients with rel/ref cHL to HDT/AHCT.

During the last century, the role of radiation therapy in the treatment of Hodgkin's disease (HD) has changed drastically. From a palliative treatment reserved for bulky lymph nodes of an incurable disease at the beginning of the century, to an exciting primary treatment used alone to cure most stages in the 1960s and 1970s, to the present more limited role as consolidation treatment after chemotherapy. Interestingly, the radiation field size has always influenced the evolution of treatment principles of HD. Over several decades, large or extended field radiotherapy has become synonymous with the successful treatment of HD. But the critical transformation from a single‐modality to a combined‐modality therapy, together with improvement in imaging and radiation planning techniques, mandates a reassessment of the delineation of appropriate radiation fields in HD. In this manuscript we review the comeback of the involved field, address design questions and offer field borders for common disease sites.

Background: Although reports have suggested that FDG-PET scans were not useful for staging of extranodal marginal zone lymphomas (MZL), experience at our center suggests otherwise. Thus we reviewed the findings of FDG-PET scans in patients with extranodal MZL seen at our center. Patients and methods: A database of 175 patients with histologically-confirmed diagnoses of extranodal MZL was reviewed. Forty-two patients who had had FDG-PET scans for initial staging were identified. All information was obtained by retrospective review of medical records and PET scans. Results: Thirty-four (81%) patients had focal tracer uptake within verified tumor sites, six (14%) patients did not, and two (5%) patients had indeterminate uptake. Seven of the 34 (21%) patients with uptake within verified tumor sites had uptake in regional lymph nodes and four patients were upstaged due to FDG-PET findings. Eight patients also obtained post-treatment FDG-PET scans. In five of those eight, the repeated FDG-PET scan indicated a complete response, and in three there was an indeterminate or mixed response. Conclusion: FDG-PET scans carried out for initial staging of extranodal MZL detected disease in a high proportion of patients. This study suggests that imaging with FDG-PET scans is useful for both initial staging and follow-up of patients with extranodal MZL.