FMISO-based Adaptive Radiotherapy for Head and Neck Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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FMISO-based Adaptive Radiotherapy for Head and Neck Cancer - a Prospective Multicenter Study

Conditions
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Head and Neck Cancer, Hypoxia, FMISO, Dose Escalation

Intervention / Treatment
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* Radiation: Dose escalation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>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/33 (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/33 LN low risk (for elective irradiation) - CTV - PTV (3mm-5mm): for dose 54 Gy/33 | Radiation: Dose escalation<br>* Dose escalation 75,9 - 79,2 Gy in 33 fractions for GTV hypoxic or any hypoxic LN > 2cm<br>|
| No Intervention: Standard fractionation<br>Standard fractionation regimen: 70 Gy/54 Gy in 33 fractions GTV primary - CTV - PTV (5+5mm): for dose 70 Gy/33 GTV LN bulky (> 3cm) - PTV (5mm): for dose 70 Gy/33 LN low risk (for elective irradiation) - CTV - PTV (3mm-5mm): for dose 54 Gy/33 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate | response rate | 2-year | 
| Locoregional progresion free survival | locoregional progresion free survival | 2-year | 
| Rate of acute (<3 months) radiation-induced events according to CTCAE 5.0 | acute radiation-induced events | 3 months | 
| Rate of late radiation-induced events according to CTCAE 5.0 | late radiation-induced events | 2-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | overall survival | 4 years | 
| Distant metastasis free survival | distant metastasis free survival | 4 years | 
| Change in QoL according to the standardised EQ-5D questionnaire | QoL according to the standardised EQ-5D questionnaire | 2 years | 
| Rate of new hypoxic areas after two weeks of radiotherapy | rate of new hypoxic areas after two weeks of radiotherapy | 2 week after start of radiotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoxia, Head and Neck Cancer, Radiotherapy, Dose escalation