Head and Neck Cancer, Hypoxia, FMISO, Dose Escalation
Conditions
Keywords
Head and Neck Cancer, Hypoxia, Radiotherapy, Dose escalation
Brief 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.
Detailed description
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
Interventions
RADIATIONDose escalation
Dose escalation 75,9 - 79,2 Gy in 33 fractions for GTV hypoxic or any hypoxic LN \> 2cm
Sponsors
Masaryk Memorial Cancer Institute
University Hospital Ostrava
University Hospital Olomouc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of late radiation-induced events according to CTCAE 5.0 | 2-year | late radiation-induced events |
| Complete response rate | 2-year | response rate |
| Locoregional progresion free survival | 2-year | locoregional progresion free survival |
| Rate of acute (<3 months) radiation-induced events according to CTCAE 5.0 | 3 months | acute radiation-induced events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 4 years | overall survival |
| Distant metastasis free survival | 4 years | distant metastasis free survival |
| Change in QoL according to the standardised EQ-5D questionnaire | 2 years | QoL according to the standardised EQ-5D questionnaire |
| Rate of new hypoxic areas after two weeks of radiotherapy | 2 week after start of radiotherapy | rate of new hypoxic areas after two weeks of radiotherapy |
Countries
Czechia
Contacts
Primary ContactMartin Dolezel, Prof
Outcome results
None listed