Assessing the Role of Radiation Therapy for Primary Mediastinal Large B-Cell Lymphoma in the Setting of PET Avid Disease after Chemotherapy

Abstract

Most patients with primary mediastinal large B-cell lymphoma (PMBCL) are treated with dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) without consolidative radiation therapy (RT), and the value of RT is poorly understood. We sought to evaluate the efficacy of RT administered to PMBCL patients with positron emission tomography–computed tomography (PET-CT) positive findings at the time of RT. We conducted a retrospective review of 22 consecutive PMBCL patients who received RT between 2008 and 2018 with residual metabolically active tumor (defined as five-point score [5PS] of 4-5) at the time of RT. Progression-free survival (PFS) and overall survival (OS) were defined from the last day of RT. The median age at diagnosis was 32 years; 68% (n = 15) were female. Frontline DA-R-EPOCH was administered to 86% (n = 19). End of frontline therapy PET-CT revealed 5PS of 4 in 32% (n = 7) and 5PS of 5 in 68% (n = 15). Biopsy was performed in 64% (n = 14), and was positive in 11 (79%) of the patients. RT was given after 1 line of systemic therapy in 59% (n = 13) and after ≥2 lines of therapy in 41% (n = 9). At the time of RT, 23% had a 5PS of 4 (n = 5) and 77% had a 5PS of 5 (n = 17). RT was delivered using a sequential or simultaneous boost to areas of PET-avid disease in 86% of cases (n = 19), with a median dose of 46.7 Gy (R 36-49.8). At a median follow-up of 6.2 years (95% CI 3.0 – 9.5), the 5-year PFS and OS were 54.5% and 76.4%, respectively. The median PFS and OS were not reached. RT resulted in a complete response (CR) rate of 64%; disease progression after RT occurred in 46% (n = 10), all in patients with 5PS of 5, with a median time of 3.0 months (range 0.8 – 6.8). Failures were in-field (n = 2), out-of-field (n = 3), or both (n = 5). PFS was significantly worse for patients with SUVmax>11.6 at the time of RT (p = 0.001), though not affected by RT dose ≥45 Gy (p = 0.47). Patients with a 5PS of 5 had significantly worse PFS compared to patients with a 5PS of 4 at the time of RT (41% vs. 100%, p = 0.04). For these patients with 5PS of 5, the median PFS was 5.3 months (95% CI 1.2 – 9.5), and a pre-RT SUVmax>11.6 was associated with inferior PFS (p = 0.02). In total, 11 patients received stem cell transplant (SCT); in 3 cases RT was given as salvage following SCT relapse. In 8 cases RT was given pre-SCT, with CR achieved due to RT before SCT in 4 patients. Overall, RT was well-tolerated with two cases (9%) of grade 3 toxicity (1 pneumonitis, 1 esophagitis). No cardiac toxicity or secondary malignancies were noted. PMBCL patients with PET avid disease after frontline immunochemotherapy pose a therapeutic challenge. RT achieved a CR in 50% of patients with PET-positive disease, but was less effective for patients with 5PS of 5. Residual SUVmax data may appropriately guide patient selection as higher activity is associated with inferior outcomes.