Impact on survival through consolidation radiotherapy for diffuse large B-cell lymphoma: a comprehensive meta-analysis

Rituximab has improved response rates and overall survival in diffuse large B-cell lymphoma. Radiotherapy is an effective treatment modality for lymphomas, but there is uncertainty on its use as consolidation after chemo-immunotherapy mainly in advanced stages. We evaluated its efficacy with a comprehensive meta-analysis and a systematic search of Pubmed, Embase, Cochrane, and abstracts from the American Society of Clinical Oncology, American Society of Hematology, European Society for Medical Oncology and American Society of Radiation Oncology published from June 1966 and December 2018. We identified 11 trials that evaluated consolidation radiotherapy following chemotherapy in a randomized fashion in 4,584 patients. The primary endpoint of this meta-analysis was progression-free survival (PFS). As three of the 11 trials were retracted, this data is based on 2,414 patients. For the primary endpoint, PFS, we found a hazard ratio (HR) 0.77 (95% Confidence Interval [CI]: 0.51-1.17), pooled (tau(2): 0.25; I(2): 85%), and a HR 0.80 (95% CI: 0.53-1.21), pooled in a bivariate metaanalysis and for the secondary endpoint, overall survival, a HR 0.93 (range, 0.61-1.40), pooled (tau(2): 0.25; I(2): 74%) and a HR 0.86 (95% CI: 0.58-1.27) in a bivariate meta-analysis. The lack of benefit did not change over time (P=0.95 (tau(2): 0.32; I(2): 88%), and was also absent for PFS when stratifying for i) chemotherapy, ii) the use of rituximab, iii) age, iv) the dose of radiotherapy and v) application to patients in complete remission with bulky disease. None of the trials used a positron emission tomography- guided approach. This meta-analysis revealed no survival benefit when consolidation radiotherapy is given to unselected diffuse large Bcell lymphoma patients following chemotherapy. These results need to be considered in future trials in the positron emission tomography-computed tomography era.