Early Response Evaluation of Proton Therapy by PET-imaging in Squamous Cell Carcinoma Located in the Head and Neck

Inclusion Criteria:

In order to be eligible to participate in this study, a subject must meet all following criteria:

* has reached adult age (≥ 18 years) at time of signing informed consent;
* is diagnosed with primary, cytologically/histologically proven, unresected invasive HNSCC;
* has at least one measurable lesion at baseline CT/MRI larger than 2 cm in diameter;
* is eligible for and thus candidate for PT ± systemic therapy with curative intent (for locally advanced HNSCC);
* has a life expectancy of at least 3 months;
* is expected able to undergo and willing to participate in all study and clinical procedures;
* has provided legal informed consent according to ICH/GCP and national/local regulations.

Exclusion Criteria:

A potential subject who meets any of the following criteria will be (secondarily) excluded:

* has known presence of distant metastases;
* suffers from paranasal sinus, salivary cancer, or thyroid malignancies;
* had prior chemotherapy within the last 3 years which is considered influencing tumour biology, proposed treatment or outcome (site investigator discretion);
* had previous surgical resection for the same disease;
* had any prior radiotherapy to the head and neck region within the last 3 years which is considered influencing tumour biology, proposed treatment or outcome (site investigator discretion);
* suffers any other prior (5 years) or current malignancy (except for basal/squamous cell skin cancer, lentigo maligna, surgically cured carcinoma in situ of the cervix, in situ breast cancer or incidental finding of stage T1a-T1b prostate cancer) or serious (psychiatric) disease at study entry that could affect the treatment, evaluation or outcome of current HSCC e.g. a Karnofsky Performance Score \<60 / ECOG Performance Status \>2 (left to the discretion of the SI entering patient in the study);
* has uncontrolled diabetes mellitus resulting in a fasting hyperglycaemia ≥11.1 mmol.L-1 (≥200 mg.dL-1) at time of 18F-FDG PET-CT and rescheduling this investigation within the set time-window is not possible. The use of short-acting insulins within 4 h of the 18F-FDG PET scan is not allowed;
* has evidence of infection localised to the neck in the 14 days prior to 18F-FDG PET-CT;
* cannot undergo each baseline PET-CT investigations within 28 days and the start of PT;
* underwent biopsy of tumour of lymph nodes in the 14 days prior to the PET-CT scan that could interfere with imaging (left to the discretion of the PI entering patient in the study);
* is unable to tolerate lying supine for the duration of a PET-CT examination;
* is known pregnant/lactating at time of PET-CT. A negative test is not obligatory;
* specific for activation PET-CT: is scheduled to be treated in Gantry-2 (nearest to PET-CT scanner), is mobile and in case of multiple beams, only patients irradiated with a maximum angle between two beams of 90º are eligible;
* suffers from (severe) claustrophobia. Low dose benzodiazepines are allowed;
* has a history of allergic reaction or hypersensitivity attributed to compounds of similar chemical or biologic composition to 18F-FDG or 18F-FAZA (extremely unlikely);
* is known with a condition resulting in high radiation sensitivity (e.g. ataxia telangiectasia, Nijmegen Breakage Syndrome, DNA LIG4-deficiency, Fanconi anaemia \[68\]);
* has a known adequate renal function (creatinine clearance ≥60 mL/min/1.73m2).
* is not proficient in the Dutch or English language or has access to unbiased translators that can aid in the study procedures or clinical questionnaires;
* is unwilling or unable to provide legal informed consent (e.g. incapacitated adult), a serious (mental) condition arises, which questions persistence of informed consent, or withdraws (part) of his/her informed consent;
* in case a patient already participates in another imaging study (especially when involving additional ionising radiation such as CT-imaging), the cumulative (radiation) burden should be discussed with the PI; Participation to other than routine PT schemes (paragraph 4.4) is not an exclusion criterion per se and should be evaluated case-by-case by the coordinating investigator.