The Circular Evolution of Treatment for Advanced Operable Stage III and IV Squamous Cell Carcinoma of the Head and Neck (SCCHN): Standard of Care History and New Data on Fractionated Cisplatin Chemoradiotherapy

Background Multimodality treatments involving radical surgery followed by high-dose cisplatin-sensitized chemoradiotherapy (SCCRT) now are standard of care for Stages III and IV SCCHN, with 5-year survival remaining 25-50%. Simultaneous fractionated cisplatin and radiation therapy (CTRT) is promising. Objective: to review SCCHN treatment history while evaluating parallel CTRT development. Methods The history of surgical, radiotherapy (RT), chemotherapy, immunotherapy, and multimodal SCCHN was reviewed. 187 Stages III/IV SCCHN CTRT patients (cisplatin 20 mg/M 2 IV 4 consecutive days weeks 1, 4, of 7000-7400 cGy (RT)) were examined. CTRT results: CCR = Clinical Complete Response–no clinical tumor. PCR = Partial Clinical Response–clinical residual tumor. HCR = Histologic Complete Response–tumor-free biopsy of primary site. Statistics: Chi-squared, ANOVA, and Kaplan-Meier. Results Fifty years of evolution in SCCHN Stage III/IV treatment identified curative surgery plus combined high-dose cisplatin/radiotherapy as standard of care, with 5-year survival <50% and significant toxicity, leading up to 40% not completing the third round of CCRT. CTRT data: All primary tumor sites included. Stage IV (74%) and Stage III (26%). T4/T3 = 89.9%. CTRT Toxicity: Grade 0 = 32.26%, 1 = 13.98%, 2 = 38.71%, 3 = 14.52%, 4 = 0.54%, and 5 = 0%. CCR overall 152/187 (81.28%). 182/187 (98%) biopsied, 145/182 HCR (79.67%). CTRT response did not vary by primary site, Stage, sex, and T category. 11 (6%) had surgery for residual disease post-CTRT. 51/187 (27.3%) recurred. Kaplan-Meier 5-year (71.58%) and 10-year (60.72%) overall survival; 5-year (63.01%) and 10-year (49.38%) disease-free survival. Discussion Advances have improved SCCHN local control, but survival remains sub-optimal. CTRT might be an alternative to surgery plus high-dose cisplatin chemoradiotherapy, potentially increasing organ preservation and survival with reduced operative morbidity and toxicity.