Mantle cell lymphoma is an aggressive B-cell lymphoma for which the biology is incompletely understood. Previous studies have reported that somatic hypermutation of the variable region of the immunoglobulin heavy chain gene (V_H), as commonly defined as <98% homology, can be detected in approximately one-third of mantle cell lymphoma, although the V_H mutation status has not been found to significantly correlate with patient survival. In this study, we assessed V_H mutation in 55 mantle cell lymphomas using a method slightly different from those used in the previous studies, and we came to different conclusions. Using DNA extracted from formalin-fixed/paraffin-embedded tumors in all cases, we identified monoclonal IGH bands in 54 of 55 cases with the FR1c/J_H primer; a monoclonal IGH band was amplified using another IGH primer set, FR256/J_H, in the remaining case. Cloning was performed in all cases, and an average of six clones were sequenced and analyzed for each case. Intraclonal heterogeneity was detected in 45 (82%) cases. Further analysis was performed in 53 cases, in which a predominant IGH species was identified. Most (32 of 53 cases, 60%) cases were ‘mutated’, with <98% homology. V_H1-69, V_H4-59 and V_H3-74 were utilized in 29 (55%) cases. Intraclonal evolution and non-productive V_H rearrangements were more frequent in the mutated group. Patients with the ‘mutated’ genotype had longer overall survival (P=0.017, Log rank) that is independent of the international prognostic index. To conclude, our data suggest that the V_H mutation frequency in mantle cell lymphoma may be higher than previously believed. Importantly, using our methodology, we found that the V_H mutation status may be a useful prognostic marker for these patients.

Oligometastases refer to a state of disease where cancer has spread beyond the primary site, but is not yet widely metastatic, often defined as 1–3 or 1–5 metastases in number. Stereotactic ablative radiotherapy (SABR) is an emerging radiotherapy technique to treat oligometastases that require further prospective population-based toxicity estimates. This is a non-randomized phase II trial where all participants will receive experimental SABR treatment to all sites of newly diagnosed or progressing oligometastatic disease. We will accrue 200 patients to assess toxicity associated with this experimental treatment. The study was powered to give a 95% confidence on the risk of late grade 4 toxicity, anticipating a < 5% rate of grade 4 toxicity. SABR treatment of oligometastases is occurring off-trial at a high rate, without sufficient evidence of its efficacy or toxicity. This trial will provide necessary toxicity data in a population-based cohort, using standardized doses and organ at risk constraints, while we await data on efficacy from randomized phase III trials. Registered through clinicaltrials.gov NCT02933242 on October 14, 2016 prospectively before patient accrual.