Clinical Trials

Inclusion Criteria:

• Age ≥ 18 years.
• Histological confirmation of a newly diagnosed non-HPV associated malignant epithelial cancer in the head and/or neck. Diagnosis requires confirmation of p16 and/or HPV DNA negativity for oropharyngeal and unknown primary sites. p16 positivity in skin cancers is allowed.
• Primary lesion located in the nasal cavity, paranasal sinuses, oral cavity, oropharynx, larynx, hypopharynx, salivary glands, lymph nodes (unknown primary or metastasis from HN-skin primary), or skin cancer where lymph node radiation is recommended.
  • NOTE: Patients with primary lesions in the larynx must have a T3 primary, bulky T2 primary (>6 cc), and/or at least 1 regional lymph node.
• Confirmation of AJCC 8th edition defined M0 established by PET/CT or PET/MRI or initial M+ disease if all metastatic sites have been resected, ablated, or treated with definitive doses of radiation.
• ECOG Performance Status (PS) 0-1 prior to initial treatment.
• Able to provide written informed consent.
• Able to complete questionnaires independently or with assistance.
• Willing to return to enrolling institution for follow-up during the observation phase.
• CBC within 8 weeks of registration with adequate marrow function defined by the following:
  • Hemoglobin > 8.0 g/dl.
  • Platelets > 100, 000 cells/mm3.
  • Absolute neutrophil count > 1500 cells/mm3.
• Covid-19 testing per institutional standard. If pre-treatment testing, patients should be negative prior to starting treatment or symptom free for at least 14 days from documented positive test. Vaccination status should be documented.

Exclusion Criteria:

• Pregnant women (serum pregnancy test required before treatment per department policy).
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy. 
  • NOTE:  Patients known to be HIV positive, but without clinical evidence of immunocompromised state, are eligible for this trial.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Other active malignancy ≤ 2 years prior to registration. 
  • EXCEPTIONS:  Non-melanotic skin cancer or carcinoma-in-situ of the cervix. 
  • NOTE:  If there is a history or prior malignancy, they must not be receiving ongoing anticancer treatment.
• History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
• Prior radiation therapy that would in the investigator’s discretion potentially increase the risk for radiation-related side effects.
• Unable to receive proton therapy because of extensive metallic hardware in close proximity to treatment site, logistical circumstances, or any other reason.
• Any of the following diagnoses: HPV-associated squamous cell carcinoma, germ cell tumors, hematologic malignancies, neuroendocrine malignancies, adenoid cystic carcinoma, sarcomas of bone, benign tumors.