De-escalation of Adjuvant Radio (Chemo) Therapy for HPV-positive Head and Neck Squamous Cell Carcinomas: A Phase I Study to Reduce Late Toxicity
In patients with squamous cell carcinoma of the oral cavity, the oropharynx and larynx with local advanced tumors (pathologic stage T3 = pT3) and or lymph node involvement (pN+) postoperative radio - or radiochemotherapy is the standard of care. Postoperative radiochemotherapy is indicated in patients with multiple lymph node metastasis, lymph node metastasis with extracapsular spread and / or residual tumor (R1-Status) after resection. Oropharyngeal cancer caused by HPV (human papillomavirus 16) is a distinct subgroup with a known sensitivity to radiotherapy (RTx) or radiochemotherapy (RCTx). Additionally a superior outcome after R(C)Tx over HPV negative patients was shown for patients treated with primary or adjuvant RCTx. To date it is unknown if the total dose of the radiotherapy can be safely reduced with the aim to decrease the therapy associated late effects. Patients with a HPV associated carcinoma that take part in the study will be treated with a reduced radiotherapy dose, chemotherapy will be prescribed based on clinical factors (number of affected lymph node, presence of extracapsular spread or residual tumor). Radiation dose will be reduced in two steps.
• Condition after surgical removal of a squamous cell carcinoma of the oropharynx and adequate lymph node dissection
• Indication for adjuvant radiotherapy or radiochemotherapy in the interdisciplinary tumor board
• Good general state (ECOG performance status 0 or 1)
• Adequate compliance to ensure closely follow-up
• Patient's consent and written consent
• Neck dissection of at least the tumor bearing side
⁃ Additional Inclusion Criteria Arm intermediate risk (at least one of the criteria must be fulfilled):
• pT3 and R0 and / or
• histologically confirmed involvement of lymph nodes (n = 1-3) and no extracapsular extension of the lymph node metastasis
⁃ Additional Inclusion Criteria Arm high risk (at least one of the criteria must be fulfilled):
• residual tumor (R1 status) and / or
• pathologic stage T4 (pT4) status and / or
• more than 3 infected lymph nodes and / or
• extracapsular extension of at least one lymph node metastasis