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.
For all patients taking part in the study the HPV status of the resected tumor will be determined centrally by p16 immunohistochemistry and confirmation will be done by HPV DNA assessment using Polymerase Chain Reaction (PCR)-based array. Patients positive for HPV will be treated with a reduced RT dose to the tumor and to elective neck. HPV negative patients will be treated with standard radio- or radiochemotherapy. Patients deemed at high risk for locoregional recurrences (presence of extracapsular spread, residual tumor or multiple affected nodes) will be treated separately from patients deemed at intermediate risk (T\>=3, and / or 1-3 nodes positive). The high risk group will be treated with a higher dose and concurrent chemotherapy. After inclusion of 30 patients per treatment group, follow up for the first 10 patients of the of the first de-escalation level will be awaited for two years and safety of the intervention will be assessed. The second de-escalation level will only be opened for accrual if less than 2 locoregional recurrences will occur within the first 10 patients per treatment group.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
304
55/ 59,4 Gy (intermediate / high risk group)
48,4/ 55 Gy (intermediate / high risk group)
60/ 66 Gy (intermediate / high risk group)
University Clinic Tübingen
Tübingen, Baden-Wurttemberg, Germany
RECRUITINGUniversity Clinic Essen
Essen, North Rhine-Westphalia, Germany
RECRUITINGUniversity Clinic Dresden
Dresden, Saxony, Germany
RECRUITINGCharité - Universitätsmedizin Berlin
Berlin, Germany
NOT_YET_RECRUITINGUniversity Clinic Frankfurt
Frankfurt am Main, Germany
RECRUITINGUniversity Clinic Freiburg
Freiburg im Breisgau, Germany
RECRUITINGUniversity Clinic Heidelberg
Heidelberg, Germany
RECRUITINGLMU Munich University Hospital
München, Germany
RECRUITINGTUM University Hospital
München, Germany
RECRUITINGUniversity Clinic Regensburg
Regensburg, Germany
RECRUITINGrate of locoregional recurrences
measured from the last day of treatment
Time frame: 24 months after end of treatment
overall survival
measured from the last day of treatment
Time frame: 60 months and 5 years after end of treatment
acute toxicity
The occurrence of acute side effects (up to 90 days after start of treatment) will be recorded and documented based on CTCAE 4.0.
Time frame: 3 months after end of treatment
late toxicity
The occurrence of late side effects will be recorded and documented based on CTCAE 4.0 after every follow-up visit.
Time frame: 24 months after end of treatment
quality of life of cancer patients
The assessment of quality of life (QoL) is carried out using the EORTC quality of life questionnaire (QLQ) C30. Quality of life will be documented immediately before the start of therapy, after completion of postoperative radiotherapy and at every follow-up visit. QOL will be measured as change from baseline over time.
Time frame: 24 months after end of treatment
quality of life - disease specific
The assessment of quality of life (QOL) is carried out using the EORTC quality of life questionnaire (QLQ) disease-specific module for head and neck cancer H\&N35. Quality of life will be documented immediately before the start of therapy, after completion of postoperative radiotherapy and at every follow-up visit. QOL will be measured as change from baseline over time.
Time frame: 24 months after end of treatment
rate of locoregional recurrences
measured from the last day of treatment
Time frame: 5 years after end of treatment
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