Biological basis for concurrent chemoradiation in head and neck cancer: Timing matters

Given that the addition of cytotoxic chemotherapy to radiation has been shown to improve overall survival and local-regional control for select patients with head and neck cancer, concurrent chemoradiation constitutes a mainstay of treatment. In pre-clinical studies, platinum-based chemotherapy, when delivered concurrently with radiation, is intended to serve as a radio-sensitizer, potentiating the cytotoxic effects of radiation on proliferating squamous cell carcinoma cells. From a biological basis, it is thus advisable that patients begin chemotherapy and radiation as synchronously as possible to optimize the benefits of dual treatment. While most guidelines for concurrent chemoradiation recommend initiating concurrent chemotherapy on day 1 of radiation (with the administration of chemotherapy preceding radiation), the actual clinical practice may vary in the timing and sequencing of these treatments. This is largely because coordination can be challenging from a logisitical and social standpoint, leading to deviations from the standard. Indeed, we recently showed that variations in the timing of how concurrent chemoradiation is delivered are signficiant and may have clinical implications.