How Should We Approach Locally Advanced Squamous Cell Carcinoma of Head and Neck Cancer Patients Ineligible for Standard Non-surgical Treatment?

Clinical criteria for CDDP ineligibility have been discussed in HNC. When considering cisplatin-based chemotherapy as part of a non-surgical approach, precise evaluation of the patient's physical condition, nutritional status, and comorbidities is needed. Upfront surgery is an important option with high curability, if a de-intensified non-surgical approach is estimated to be unavoidable. Although no prospective data are available regarding alternatives to definitive cisplatin-based combination therapy for patients undergoing a non-surgical approach, cetuximab, carboplatin, or split-dose cisplatin-based regimens may be employed for cisplatin-ineligible patients in clinical practice. The combination of immune checkpoint inhibitors with radiotherapy may be a promising novel approach, and some trials are currently targeting the specific cohort of patients ineligible for high-dose cisplatin. There are no standard treatments for patients ineligible for high-dose cisplatin. A personalized treatment strategy should be proposed based on the individual benefit-to-risk ratio of each treatment option in patients ineligible for the standard of care. Prospective clinical trials for cisplatin-ineligible patients with locally advanced HNC still need to be performed.