Biological and clinical implications for multimodality treatment in patients affected by squamous cell carcinoma of the head and neck

Aims and background: Several strategies combining radiotherapy and chemotherapy have been developed for the cure of squamous cell carcinoma of the head and neck (SCC-HN) in an attempt to improve loco-regional control and survival. This overview aims to summarize clinical results of reported randomized trials and to discuss the biological mechanisms underlying the interactive and non-interactive processes promoted when chemotherapy is added to radiotherapy. Methods: The clinical goals of combined modality therapy and exploitable associations of chemotherapy and radiotherapy that may lead to a therapeutic gain in comparison with radiotherapy alone are reported and reviewed. Clinical applications of the four main ways of combining chemotherapy with radiotherapy (neoadjuvant, concomitant, alternating and adjuvant) are briefly re-analyzed and discussed. Results and Conclusions: Published evidence suggests that induction chemotherapy (ne-adjuvant) should not be routinely recommended; however, induction chemotherapy increases the likelihood of larynx preservation in patients with laryngeal and hypopharyngeal cancer and should be offered as a treatment option as an alternative to surgery. Positive results of several randomized studies and a recent meta-analysis show that concomitant use of chemotherapy and radiotherapy in unresectable SCC-HN is beneficial and should be considered as a potential standard treatment. A complementary biological staging of SCC- HN, by evaluating new predictive factors of tumor response, is presently under investigation to better interpretate clinical randomized trials exploring chemo-radiotherapy.