Dose-Escalated Hypofractionated Adaptive Radiotherapy for Head and Neck Cancer

Inclusion Criteria

• Age ≥18 years
• Diagnosis of T3-T4 N0-N3 M0 or T0-T4 N1-N3 M0 squamous cell carcinoma of the head and neck squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of unknown head/neck primary) based on American Joint Committee on Cancer guideline (AJCC; 8th edition) with measurable disease who meet at least 1 one of the following 3 criteria:
• Not a candidates for concurrent, bolus, cisplatin-based chemoradiation therapy based on one of the following criteria (a-e)
• Age ≥ 70 with moderate to severe comorbidity or vulnerability to cisplatin, defined as having one or more of the following conditions within 4 week of registration:
• Modified Charlson Comorbidity Index ≥ 1
• Adult Comorbidity Evaluation-27 (ACE-27) Index ≥ 1
• ω score 3
• Inability to encompass all gross disease in 19 cm superior to inferior planning target volume to be treated on the MR LINAC
• MRI-incompatible foreign body
• Claustrophobia precluding ability to tolerate multiple MRIs
• MRI-incompatible pacemaker or implantable cardioverter defibrillator (ICD) placement
• Patients with Cochlear implant
• Patients with prior radiation therapy to the head and neck Note: Prior external beam radiotherapy is excluded, but Iodine 131 is allowed.
• Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer
• Major surgery within 28 days prior to registration
• Body weight ≤ 30 kg
• Any of the following severe laboratory abnormalities within 14 days of registration, unless corrected prior to it: Sodium 155 mmol/L; Potassium 6 mmol/L ;Fasting glucose 400 mg/dl;Serum calcium (ionized or adjusted for albumin) 12.5 mg/dl; Magnesium 3 mg/dl
• Unstable angina and/or congestive heart failure requiring hospitalization within 3 months prior to Step 1 registration
• Transmural myocardial infarction within 3 months prior to Step 1 registration
• Respiratory illness requiring hospitalization at the time of Step 1 registration
• Note: If the respiratory illness is resolved and the patient meets the eligibility status above, then the patient can be considered for the trial.
• Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to Step 1 registration
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Clinically apparent jaundice and/or known coagulation defects
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion: Patients with vitiligo or alopecia; Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; Any chronic skin condition that does not require systemic therapy; Patients without active disease in the last 5 years may be included but only after consultation with the medical oncology study chair; Patients with celiac disease controlled by diet alone.
• History of active primary immunodeficiency including, but not limited to Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition. The need to exclude patients with AIDS from this protocol is necessary because the treatment involved in this protocol may be immunosuppressive. Patients with known HIV, cluster of differentiation 4 (CD4) cell counts ≥ 200/μL, and undetectable viral loads who are stable on an antiretroviral regimen may be included.
• Current or prior use of immunosuppressive medication within 14 days before registration, with the exceptions of intranasal and inhaled corticosteroids or systemic corti