Image-guided Proton Therapy for the Treatment of Locally Advanced Unresectable Head and Neck Cancer

Inclusion Criteria:

* Biopsy proven diagnosis of squamous cell carcinoma of head and neck cancer originating in the oropharynx, hypopharynx, larynx, oral cavity (base of tongue) or nasopharynx. Clinical evidence should be documented, and may consist of imaging, endoscopic evaluation, palpation, and should be sufficient to estimate the image tumor characteristic of the primary tumor
* Negative for HPV by p16 immunohistochemistry (IHC) or in situ hybridization (ISH)
* Inoperable locally advances disease, i.e. stage \>= III and T stage \>= 2
* The primary radiotherapy, either in combination with chemotherapy or not, with curative intent
* No head and neck surgery of the primary tumor or lymph nodes except for incisional or excisional biopsies
* Eastern Cooperative Oncology Group (ECOG) = 0, 1, or 2
* For females of child-bearing age, a negative pregnancy test

Exclusion Criteria:

* Patients who have undergone definitive resection of their primary or nodal disease as well as any chemotherapy or radiation therapy for their head and neck squamous cell carcinoma (HNSCC)
* Patient that refuse or are unable to stop smoking and/or consuming alcohol during and after radiotherapy. In addition, patients that refuse or fail tobacco and alcohol blood test
* Patients that have no detectable no tumor in both the primary site and lymph nodes at week 4 in treatment, because there will not be a volume to boost
* Patients unable or unwilling to give written, informed consent or to undergo magnetic resonance imaging (MRI) imaging
* Women of childbearing potential (a woman of child-bearing potential is a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months \[i.e., who has had menses at any time in the preceding 24 consecutive months\]). Male partners must practice effective contraception (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study
* Patients unable to tolerate intravenous contrast for both computed tomography (CT) and MRI, having an estimated glomerular filtration rate (GFR) \< 60 ml/min/1.73 m\^2 or any contraindications to gadolinium-based contrast agents
* Contraindications to iron supplementation include hemochromatosis, colitis, history of gastrointestinal (GI) bleeds, alcoholism, or liver disease. Ferumoxytol is contraindicated in patients with evidence of iron overload and/or known hypersensitivity to Feraheme or any of its components. Consequently, we will plan to exclude patients who have symptoms or signs that might be caused by iron overload. These include patients with (unexplained): arthritis (including premature osteoarthritis), congestive heart failure or cardiomyopathy, adult-onset diabetes, secondary hypogonadism, increased skin pigmentation, or patients with persistently elevated serum ferritin not explained by an underlying inflammatory/systemic disease, unless these patients demonstrate a fasting transferrin saturation =\< 0.45
* Patients with any evidence of iron overload on pre-imaging laboratory studies