PRIMARY MEDIASTINAL LARGE B‐CELL LYMPHOMA—THE ROLE OF MEDIASTINAL RADIATION

Introduction: Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare subtype of diffuse large B-cell lymphoma. The most standard approaches include a combination of immunochemotherapy and mediastinal radiotherapy (RT). Because mediastinal RT is associated with significant long-term toxicities, it was necessary the development of effective therapeutic strategies (rituximab with increased dose intensity regimens) that changed the need for routine RT. Patients and Methods: Fifteen patients with diagnosis of PMLBCL between 2005 and 2015 were treated according to protocol DA-R-EPOCH (infusional dose-adjusted etoposide, doxorubicin and cyclophosphamide with vincristine, prednisone and rituximab). Patients were classified into 3 risk groups (according to presence of pleural/pericardial effusion and IPI high/intermediate-risk or high-risk). Residual disease (RD) was evaluated by FDG-PET and defined as score 2 according to Deauville Criteria and partial response (PR) defined as score 4–5 with a reduction >50% in size of mass. Results: Median age at diagnosis was 29 (21–43) years, age <40 years in 86.7% (n = 13). Eleven patients (78.6%, n = 14) had a bulky disease (tumor mass ≥ 10 cm), and 6 (42.9%, n = 14) had superior vena cava syndrome at presentation. Presence of pleural/pericardial effusion in 7 patients (53.8%, n = 13) and pulmonary involvement in 5 (38.5%, n = 13). According to the prognostic score, two patients (15.4%) were classified as high risk (2 adverse factors), five (38.5%) in intermediate risk (1 factor) and six (42.2%) in low risk (0 factors). All patients were treated with 6 cycles of immunochemotherapy. Seven patients (46.7%) achieved complete response (CR), confirmed by FDG-PET in five. Another 3 (20%) had RD. All patients who achieved CR/RD did not perform RT with an event-free survival (EFS) of 100%. PR was attained in 3 patients (20%), two had high-risk disease. All patients in PR were submitted to RT, reaching CR (confirmed by FDG-PET) without relapse during the follow-up time. Progressive/stable disease was observed in 2 patients (13.3%). They were submitted to autologous stem cell transplant reaching CR. With a median follow-up of 52 (14–116) months, it was obtained an overall survival/EFS of 100% without evidence of disease. No cardiac events or second tumors were observed, so far. Conclusion: The use of therapeutic approaches with rituximab and increased dose intensity regimens (like DA-R-EPOCH) has shown excellent efficacy and challenge the need for mediastinal radiation (5-year OS and EFS >90%, according to data from several studies). In conclusion, our results indicate that patients who had CR/RD evaluated by FDG-PET after treatment with DA-R-EPOCH, EFS was 100% with a median follow up of 52 months. In these patients, the use of DA-R-EPOCH obviated the need for routine mediastinal RT. In patients with persistent disease after treatment, RT is a necessary approach though. Keywords: DA-R-EPOCH; primary mediastinal large B-cell lymphoma (PMLBCL).