individualized radiation dose prescription in hnscc based on f-miso-pet hypoxia-imaging

Conditions: Head and Neck Squamous Cell Carcinoma

Summary: the trial evaluates the value of radiation dose escalation based on hypoxia detection by 18f_misonidazole positron emission tomography (18f-miso-pet) for primary radiochemotherapy of head and neck squamous cell carcinoma. patients negative for human papillomavirus (hpv) and with hypoxic tumours after 2 weeks of radiochemotherapy are randomized to completion of standard radiochemotherapy or radiochemotherapy with escalated radiation dose. an additional interventional arm includes a carbon ion boost. hpv positive tumours can be included in a control arm. primary endpoint is local tumour control 2 years after radiochemotherapy.

previous preclinical data and a prospective validated patient cohort have shown that patients with head and neck squamous cell carcinoma, whose tumours are hypoxic after 2 weeks of primary radiochmeotherapy, have a significantly lower chance of locoregional tumour control. the multi-center trial evaluates the value of radiation dose escalation based on hypoxia detection by 18f_misonidazole positron emission tomography (18f-miso-pet) for primary radiochemotherapy of head and neck squamous cell carcinoma. patients negative for human papillomavirus (hpv) and with hypoxic tumours after 2 weeks of radiochemotherapy are randomized to completion of standard radiochemotherapy (70 gy) or radiochemotherapy with escalated radiation dose (77 gy). an additional interventional arm includes a carbon ion boost to 77 gy. hpv positive tumours can be included in a control arm. primary endpoint is local tumour control 2 years after radiochemotherapy. secondary endpoints include acute and late toxicity (ctcae 5.0), regional tumor control, overall survival, disease free survival, distant metastases, kinetics analysis of dynamic fmiso-pet scans, quality of life (qol). the hypothesis is that local tumour control 2 years after radiochemotherapy is higher in the dose escalated compared to the control arm.

Eligibility criteria:
inclusion criteria: * age: older than 18 years * who (ecog) performance status 0-2 * histological proven hnscc * hpv negative tumors or hpv positive tumors * stage iii, iva or ivb hnscc according to uicc and ajcc guidelines * tumor classified as irresectable or patient inoperable or patient refused surgery * tumor extension and localization suitable for radiochemotherapy with curative intent * simultaneous standard chemotherapy with cisplatin applicable (no contra-indications) * dental examination and -treatment before start of therapy * for women with childbearing potential and men in reproductive ages adequate contraception. * ability of subject to understand character and individual consequences of the clinical trial * written informed consent (must be available before enrolment in the trial) exclusion criteria: * refusal of the patients to take part in the trial * presence of distant metastases (uicc stage ivc) * previous radiotherapy in the head and neck region * second malignancy that is likely to require treatment during the trial intervention or follow-up period or that, in the opinion of the physician, has a considerable risk of recurrence or metastases within the follow-up period * serious disease or medical condition with life expectancy of less than one year * participation in competing interventional trial on cancer treatment * patients who are not suitable for radiochemotherapy * pregnant or lactating women * patients not able to understand the character and individual consequences of the trial * nasopharyngeal carcinomas

Keywords: head and neck cancer radiochemotherapy hpv