Improved response and survival to combined cisplatin and radiation in non-keratinizing squamous cell carcinomas of the head and neck. An RTOG study of 114 advanced stage tumors

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Abstract
Effective treatment modalities for Stage III and IV squamous cell carcinomas (SCC) of the head and neck are limited and seldom result in long term survival. The improved results with cisplatin containing chemotherapy have been encouraging and represent an additional therapeutic modality for head and neck cancer. To estimate the effectiveness of concommitant radiation and cisplatin chemotherapy, the Radiation Therapy Oncology Group (RTOG) initiated a Phase II study for patients with advanced nonresectable SCC of the head and neck. In addition, the diagnostic biopsy specimens were collected. Two pathologists reviewed and scored the biopsy specimens for a number of histologic parameters, including degree of keratinization, nuclear pleomorphism, frequency of mitoses, inflammatory and stromal reaction, pattern of invasion and vascular involvement in order to identify potential prognostically important patient subgroups. A total of 114 patients were evaluated for complete clinical responses (CR). These were achieved in 76% for all head and neck sites (ALL), and in 72% of the patients excluding nasopharyngeal and sinus cancers (REST). Evaluation of histopathologic parameters through multivariate analysis identified the presence of keratin as the most significant in predicting CR. Non‐keratinizing SCC had CRs of 98% (ALL), and 94% (REST), as compared with 64% and 67% in the patients with keratin producing neoplasms (P < 0.001 and 0.05) respectively. Survival at 24 months was found to be improved in the non‐keratinizing SCC (P = 0.002). Multivariate analysis also identified the frequency of mitoses as being important in predicting for CR in patients with keratin in the biopsy findings. Biopsy specimens from ALL patients with two or more mitotic figures per high‐power microscopic field had 76% CRs, in comparison with 46% when none or one mitotic figure was observed (P = 0.02). In the restricted group of patients (REST), the CR was 77% in the high mitotic figure group as opposed to 45% in the lower rate group (P = 0.03). However, this significant difference in CR rates did not translate into improved survival for the high CR subset.