Can probiotics be a potential game-changer in reducing mucosal toxicity during head and neck radiotherapy?

Objective: Radiation-induced mucositis (RIM) is an important cause of unplanned treatment breaks during definitive chemo-radiotherapy (CTRT) in locally advanced head-neck cancers (LAHNC). The accelerated repopulation that can occur during this period has proven to significantly compromise local control. Probiotics are currently being evaluated as immunomodulators that, in addition to anti-inflammatory effects, maintain the integrity of mucosal barriers. The current study intends to identify the possible mechanisms by which probiotics can reduce the most important treatment compromising toxicity of radical CTRT, that is, RIM. It is also intended to explore the additional immune enhancement that probiotics can provide by quantifying CD4 T and CD8 T during the course of treatment. Materials and Methods: Patients with LAHNC were randomized to the probiotic arm (A) or control arm (B). A radical dose of 70 Gy equivalent was planned with concurrent platinum-based chemotherapy. All patients underwent CD4 T and CD8 T cell counting pre- and post-completion of treatment. RIM was documented and analyzed in both arms. Results: 31 patients were enrolled; arm A (n=9/15) and arm B (n=15/16) were available for analysis. Arm A showed a 57% relative reduction in grade 3 mucositis compared to Arm B. The mean weight loss in Arm A was 4.6 ± 3.08 kg vs. Arm B was 7 ± 2.3 kg (p = 0.05). A complete response was noted in Arm A at 77% (7/9) vs. Arm B at 33% (5/15). A fall in the CD4 T cell proportion of A = 9% (p=0.08) and B = 5% (p=0.05) was noted post-CTRT. CD8 T cell proportion rose by A = 13% (p=0.04) and B = 10% (p=0.001). Conclusions: Probiotics reduce RIM in LAHNC and enhance the antitumor CD8 T cells, thus suggesting a window for an affordable, non-toxic immunomodulator.