Integrating surgery into treatment paradigms for organ preservation: tailoring treatment to biology improves outcomes.

Abstract

Neoadjuvant chemotherapy was introduced into treatment paradigms for curable head and neck cancer in the early 1970s in an effort to reduce the magnitude of mutilating surgery and to provide a rationale for adjuvant systemic chemotherapy in patients who responded to initial chemotherapy. The large number of trials that followed failed to demonstrate improved survival when neoadjuvant chemotherapy was added to conventional surgery or radiation. Importantly, a consistent observation in these neoadjuvant trials was the significant association of clinical tumor response to neoadjuvant therapy and favorable prognosis. The findings led to development of a new treatment paradigm that was based on the hypothesis that the biology of an individual cancer is more predictive of response to specific therapy and overall outcome than is anatomic tumor site or extent, and on the corollary that matching treatment modality to biology will improve overall survival rates. This report identifies key findings that are important in the design and analysis of organ preservation trials and biologic markers predictive of response and outcomes. Ongoing studies incorporating biomarkers such as p53, Bcl-xL, HPV, EGFR, COX-2, and tumor promoter gene methylation are underway and will identify new targets for molecular manipulation, response monitoring, and tumor imaging that could allow real-time changes in how we integrate the various components of multi-modal therapy.