The relevance of tumor size and cell kinetics as predictors of radiation response in head and neck cancer.A randomized study on the effect of intraarterial chemotherapy followed by radiotherapy

Abstract

Size and extent of a primary tumor strongly influences its response to irradiation. In order to investigate the relevance of this statement a randomized study was carried out in which irradiation of advanced carcinoma of head and neck was compared with a combined treatment where preirradiation intraarterial chemotherapy was administered in order to reduce the extent of the tumor. Intra-arterial chemotherapy (MTX 3–5 mg/day for 25–35 days) was given to 72 cases with lesions in the oral cavity, the oropharynx and maxillary antrum. Depending on response the patients were restaged and submitted to radiotherapy. In 68 other cases randomly allocated, radiotherapy only was given with the same modality and technique. After chemotherapy 21 cases with intraoral and 14 cases with maxillary antrum and oropharynx cancers were classified Stage I and II (0 and 23, respectively, before treatment). Results after 4 years follow up showed both local control and survival statistically better in the combined treatment in intraoral cancer where irradiation was delivered by a combination of external and interstitial technique. In the other cases no statistically significant difference was found. Amelioration of the results in the oral cavity could be ascribed to the greater use of interstitial irradiation due to the tumor shrinkage obtained with preirradiation chemotherapy more than to some synergistic effect between drug and irradiation. In 8 cases tumor cell kinetics were performed and the nuclear DNA content measured, but none of the kinetic parameters could be correlated with the response to treatment, even when the cancers were grouped according to their clinical growth characteristics. Late results in the irradiation of head and neck cancer probably depends on the presence of some resistant component which cannot be predicted by the cell kinetic or nuclear DNA content. Surgical excision or a second course of chemotherapy must be considered as a part of the multimodality treatment.