fmiso-based adaptive radiotherapy for head and neck cancer

Conditions: Head and Neck Cancer; Hypoxia; FMISO; Dose Escalation

Summary: hypoxia occurs in about 80% of head and neck tumors. based on experimental and clinical data, hypoxia is a useful parameter for pretherapeutic stratification. these radioresistant regions can be detected with fmiso pet/ct. moreover, hypoxic subvolumes of tumors can be evolving as target volumes for radiotherapy ("dose painting") in hypoxia imaging-based dose escalation.

the radiotherapy protocol will include two dose-escalation regimens. the dose in hypoxic tumor volume will be escalated either by conventional rt or stereotactic radiotherapy technique. concurrent chemotherapy cisplatin will be administered weekly 35-40 mg/m2 or every three weeks 80-100 mg/m2. the parameter of cumulative cisplatin dose of 200 mg/m2 during the whole course of radiotherapy will be also taken into account. patients will be examined and monitored at least every two weeks. target volumes and dose and fractionation: definition of gross tumor volumes (gtv), clinical target volumes (ctv) and planning target volumes (ptv) will follow recommendations of dahanca, eortc and rtog guidelines. the conventional radiotherapy protocol: standard fractionation regimen: 70 gy/54 gy in 33 fractions gtv primary - ctv - ptv (5+5mm): for dose 70 gy in 33 fractions gtv ln bulky (\> 3cm) - ptv (5mm): for dose 70 gy in 33 fractions ln low risk (for elective irradiation) - ctv - ptv (3mm-5mm): for dose 54 gy in 33 fractions dose escalated radiotherapy protocol: dose escalated radiotherapy protocol: 75,9 - 79,2 gy in 33 fractions gtv hypoxic or any hypoxic ln \> 2cm - ptv (0mm): dose 75,9 - 79,2 gy in 33 fractions (contours must be subtracted and reduce by 3mm in case of close relation to the skin, bones or large blood vessels) gtv primary - ctv - ptv (5+5mm): for dose 70 gy in 33 fractions ln low risk (for elective irradiation) - ctv - ptv (3mm-5mm): for dose 54 gy in 33 fractions

Eligibility criteria:
inclusion criteria: * pathologically proven new diagnosis of oropharyngeal p16 negative, or laryngeal, hypopharyngeal, oral cavity (independent of p16) squamous cell carcinoma of clinical stage iii, iv confined to head and neck area * evaluable tumor burden assessed by computed tomography scan or magnetic resonance imaging, based on recist (response evaluation criteria in solid tumours) version 1.1 * eligibiity for definitive chemoradiation or hyperfractionated accelerated radiotherapy * eastern cooperative oncology group (ecog) performance status of 0 or 1 * adequate kidney and liver function exclusion criteria: * prior surgical treatment - any surgery of primary tumor or involved nodes or prior surgical debulking apart from surgery with diagnostic intention (e.g. open biopsy if necessary) * prior systemic therapy, targeted therapy, radiotherapy treatment for head and neck cancer * cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or unknown primary head and neck cancer * known active central nervous system (cns) metastases and/or carcinomatous meningitis or any distant metastasis * known active hepatitis b or c * history of human immunodeficiency virus (hiv) * history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization * previous allogeneic tissue/solid organ transplant * active infection requiring systemic therapy

Keywords: head and neck cancer hypoxia radiotherapy dose escalation