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Nasopharyngeal carcinoma is known to be highly chemo and radiosensitive and radiotherapy with chemotherapy remains the standard of treatment. Local control has been shown to correlate with the total delivered radiation dose up to 80Gy. However, the dose escalation was associated with additional toxicity. In advanced inoperable oral cavity carcinomas the conventional radiotherapy and chemotherapy regimens have reported poor outcomes. A higher biologically effective dose to the primary tumor is required to improve outcomes. The dose escalation with standard IMRT techniques may be limited by the volume of irradiated organs at risk. Historically brachytherapy in combination with EBRT was an effective technique for dose escalation, but in technically or medically unfeasible cases (large tumor, contraindication to invasive procedures) an image-guided stereotactic radiotherapy technique is a new alternative promising treatment option. We evaluated the efficacy and toxicity of stereotactic hypofractionated boost in combination with EBRT in the treatment of advanced stage of nasopharyngeal and oral cavity cancer.

Between March 2011 and October 2018, twenty-eight patients with nasopharyngeal cancer stage III-IVA and thirty-seven patients with squamous cell carcinoma (p16 negative) of the oral cavity stage IVA-IVB, ineligible for surgical treatment were indicated for radiochemotherapy or hyperfractionated accelerated radiotherapy (HART). Concurrent chemotherapy cisplatin 40mg/m2 weekly was used. The radiotherapy protocol combined EBRT and stereotactic boost to the primary tumor. The dose delivered from EBRT was 70-72.5Gy in 35/50 fractions. The stereotactic boost followed EBRT course with 5-10Gy in 1-2 fractions. For the variables (tumor volume, stage , grade) a multivariate analysis was performed to find the relationship between overall survival, local progression and metastasis. Toxicity was evaluated according to CTCAE scale version 4.

Complete remission was reached in 93% (26 patients) with nasopharyngeal cancer and 62% (23 patients) with oral cavity cancer. None of the patients required reirradiation. The 5y-OS was 75% in nasopharyngeal cancer and 27% in patients with oral cavity cancer. Statistical analysis revealed that larger tumors had worse overall survival and a greater chance of metastasis. Log-Rank GTV >44ccm (HR=1.96; [95% CI(0.87; 4.38)]; p=0.11). The maximum acute toxicity was grade 3 mucositis and dysphagia, manifested in 14 (22%) patients with oral cavity cancer and 4 (14%) patients with nasopharyngeal cancer. Late radiation toxicity manifested as osteonecrosis in 3(8%) and dysphagia 11(30%) in patients with oral cavity cancer. And hearing impairment in 3(11%), difficulty chewing and dysphagia in 6(21%) patients with nasopharyngeal cancer.

Stereotactic hypofractionated boost seems to be a viable option for dose escalation in patients with advanced stages of nasopharyngeal and oral cavity cancer. Dose escalation related toxicity was mild.