Lattice-Based Radiotherapy and Chemo-Immunotherapy for Oral Cavity Squamous Cell Carcinoma

Inclusion Criteria: * Non-metastatic, pathologically confirmed oral cavity squamous cell carcinoma, cT3-T4a cN0-N3 or cT1-T2 cN1-N3. Histologic variants will be included (papillary squamous cell carcinoma and basaloid squamous cell carcinoma, e.g.). Cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oral cavity (oral tongue, floor of mouth, alveolar ridge, buccal or lip, i.e.) * Surgically resectable * Zubrod Performance Status of 0-1 * (Phase I) Primary and lymph node ≥ 3 cm * (Phase II) Primary and lymph node ≥ 3 cm OR Primary ≥ 3 cm * Patients must provide their personal smoking history prior to registration. * Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy. Female subjects of childbearing potential who are undergoing RT or who are partners to male subjects in the study should avoid sexual activity or use a highly effective method of birth control during sexual intercourse. Acceptable, highly effective methods of birth control include: intrauterine device (IUD)/intrauterine hormone releasing system (IUS), bilateral tube occlusion, vasectomized partner, combined (estrogen and progesterone containing) or progesterone-only hormonal contraceptives (oral, intravaginal, transdermal, injectable). * Males who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception (abstinence/protection) for the duration of treatment/study participation. * The patient must provide study-specific informed consent prior to study entry. * Adequate renal function within 2 weeks prior to registration * Adequate hematologic function within 2 weeks prior to registration * Patients who are HIV positive but who have no prior AIDS-defining illness and have CD4 cells of at least 350/mm3 are eligible. HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions. Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B). Exclusion Criteria: * Cancers considered to be primarily located in the oropharynx even if p16 negative * Carcinoma of the neck of unknown primary site origin (even if p16 negative) * Distant metastasis or adenopathy below the clavicles; * Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. * Simultaneous primary cancers or separate bilateral primary tumor sites; * Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible); * Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; * Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields; * Severe, active co-morbidity * Pregnancy; this exclusion is necessary because the treatment in this study may be significantly teratogenic * Prior allergic reaction to cisplatin * Exclusion Criteria for MRI: Normal MRI exclusion criteria will apply, including those on the following list. A standard MRI safety form will be used to identify potential conditions warranting exclusion. 1. Electrical implants such as cardiac pacemakers or perfusion pumps 2. Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial heart, valves with steel parts, metal fragments, shrapnel, bullets, tattoos near the eye, or steel implants 3. Ferromagnetic objects such as jewelry or metal clips in clothing 4. Claustrophobia 5. History of seizures