Radiation Therapy and Cisplatin With or Without Surgery in Treating Patients With Stage III-IV Oropharyngeal Cancer

This randomized phase II trial studies radiation therapy and cisplatin with or without surgery in treating patients with stage III-IV oropharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with radiation therapy may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without surgery in treating patients with oropharyngeal cancer.

PRIMARY OBJECTIVES:

I. To determine if primary treatment with transoral endoscopic head and neck surgery will improve progression free survival (PFS) for patients with human papilloma virus negative (HPV-) oropharyngeal cancer (OPC).

SECONDARY OBJECTIVES:

I. To compare patterns of failure (local-regional relapse versus distant) and survival (overall and progression-free).

II. To determine the safety and efficacy (rate of positive surgical margins) of using transoral robotic surgery for patients with T3 tumors of the tonsil, tongue-base, or glossopharyngeal sulcus.

III. To compare head and neck cancer-specific quality of life (QOL) short-term (\< 6 months) and long-term (2 years) relating to swallowing function.

IV. To compare subjective (patient reported) and objective (physiologic) measures of swallowing function short-term and long-term.

V. To assess effect of neck dissection on shoulder function using a validated QOL instrument for patients undergoing neck dissection VI. To assess the correlation of physician derived clinical target volumes (CTV's) with locoregional control or failure.

VII. To determine whether specific molecular profiles are associated with overall or progression-free survival or other clinical endpoints.

VIII. To determine the sensitivity and specificity of pre-treatment computed tomography (CT) scans detecting the presence of lymph node extracapsular extension by examining the surgically dissected lymph nodes.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo transoral endoscopic head and neck surgery (eHNS). Depending on post-operative pathology findings, patients may undergo intensity modulated radiation therapy (IMRT) once daily (QD) five days a week for 6 weeks. High-risk patients also receive cisplatin intravenously (IV) on days 1, 8, 15, 22, 29, and 36 during radiation therapy.

ARM II: Patients undergo IMRT QD five days a week for 7 weeks. Patients also receive cisplatin IV on days 1, 8, 15, 22, 29, and 36 during radiation therapy.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Eligibility Criteria:
Inclusion Criteria:

* Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the oropharynx, localized to the tonsil, glossopharyngeal sulcus, and tongue-base within 6 weeks (42 days) of registration
* The primary tumor must be resectable through a transoral endoscopic head and neck surgery with anticipation of resection free margins (resection does not require total or subtotal glossectomy or total laryngectomy); specifically, patients must (1) not have trismus, (2) not have interincisor opening less than 2.5 cm, and (3) not have poor transoral exposure of the tumor itself nor surrounding soft-tissue margins, regardless of etiology
* Clinical stage III-IV; T1-2, N1-2b; T3, N0-2b, with only well-lateralized exophytic T3 tumors not approaching within 1 cm of midline, and amenable to transoral eHNS
* p16 protein (p16) negative by immunohistochemistry (documented by the institution's pre-enrollment biomarker screening at a Clinical Laboratory Improvement Amendments \[CLIA\]-certified lab), defined as absent, weak, and/or only focal nuclear and cytoplasmic staining in less than 70% of the tumor cells
* Appropriate stage for protocol entry, including no distant metastases or adenopathy below the clavicles, based upon the following minimum diagnostic workup:

  * History/physical examination by the treating physician (radiation oncologist, medical oncologist, or head and neck surgeon) within 30 days prior to registration
  * Imaging of the head and neck (CT with contrast, positron emission tomography \[PET\]/CT, and/or magnetic resonance imaging \[MRI\]) within 30 days prior to registration; a CT scan with contrast is mandatory (unless contraindicated, e.g. contrast allergy, etc.); note that a PET/CT scan alone (unless performed with contrast) is not sufficient
  * Chest CT scan (with or without contrast) or PET/CT of chest (with or without contrast) within 30 days prior to registration
  * Modified barium swallow (MBS) to assess swallowing function within 30 days prior to registration
  * Preoperative Mallampati assessment as documented by attending surgeon within 30 days prior to registration
* Zubrod performance status 0-1 within 30 days prior to registration
* Absolute neutrophil count (ANC) \>= 1,800 cells/mm\^3 based upon complete blood count (CBC)/differential
* Platelets \>= 100,000 cells/mm\^3 based upon CBC/differential
* Hemoglobin \>= 8.0 g/dl based upon CBC/differential (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 8.0 g/dl is acceptable)
* Total bilirubin =\< 2 mg/dl
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x the upper limit of normal
* Serum creatinine =\< 1.5 mg/dl and/or creatinine clearance (CC) \>= 50 ml/min; CC can be determined by 24-hour collection or estimated by Cockcroft-Gault formula
* Serum pregnancy test within 14 days prior to registration for women of childbearing potential
* Women of childbearing potential and male participants who are sexually active must practice medically effective contraception during treatment and for 42 days following completion of treatment
* Patient must be able to provide study-specific informed consent prior to study entry

Exclusion Criteria:

* 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 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, defined as follows:

  * \> 2 based on the American Society of Anesthesiologists (ASA) physical status classification system
  * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  * Transmural myocardial infarction within the last 6 months
  * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
  * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  * Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive; protocol-specific requirements may also exclude immuno-compromised patients
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
* Prior allergic reaction to cisplatin
* Radiographic evidence of retropharyngeal metastasis