Individualized Treatment in Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA

Inclusion Criteria:

* Biopsy proven (from primary lesion and/or lymph nodes) diagnosis of cancer of the nasopharynx
* Sites are required to complete Step 1 registration before submitting specimens for EBV DNA analysis

  * Patients must have detectable pretreatment plasma EBV DNA, determined by the central lab prior to Step 2 registration
  * For patients who have detectable plasma EBV DNA tested at one of the credentialed central labs within 28 days prior to Step 1 registration: that test result can be used for eligibility without the need for re-testing; to use this test result for eligibility, the central lab must enter the test result through the pathology portal
* Stage II-IVB disease (American Joint Committee on Cancer \[AJCC\], 7th edition \[ed.\]) with no evidence of distant metastasis, based upon the following minimum diagnostic workup:

  * History/physical examination by a Medical Oncologist or Clinical Oncologist or Radiation Oncologist or Ear, Nose, Throat specialist (ENT), which must include an endoscopic evaluation, a complete list of current medications, and assessment of weight and weight loss in the past 6 months within 21 days prior to registration
  * Evaluation of tumor extent required within 28 days prior to registration:

    * Magnetic resonance imaging (MRI) of the nasopharynx and neck; or computed tomography (CT) of the nasopharynx and neck with =\< 3 mm contiguous slices with contrast and bone windows (to evaluate base of skull involvement).

      * Note: If a treatment planning CT scan is used, it must be with =\< 3 mm contiguous slices with contrast and be read by a radiologist
  * To rule out distant metastasis, patients must undergo the following imaging within 28 days prior to registration:

    * A CT scan with contrast of the chest and abdomen (required), and the pelvis (optional), or a total body PET/CT scan (non-contrast PET/CT is acceptable)
    * A bone scan only when there is suspicion of bone metastases (a PET/CT scan can substitute for the bone scan)
* Zubrod performance status 0-1 within 21 days prior to registration
* Age \>= 18
* Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (within 21 days prior to registration)
* Platelets \>= 100,000 cells/mm\^3 (within 21 days prior to registration)
* Hemoglobin \>= 8.0 g/dl (within 21 days prior to registration) (Note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 8.0 g/dl is acceptable)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 21 days prior to registration)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 1.5 x institutional ULN (within 21 days prior to registration)
* Alkaline phosphatase =\< 1.5 x institutional ULN (within 21 days prior to registration)
* Serum creatinine =\< 1.5 mg/dl or calculated creatinine clearance (CC) \>= 50 ml/min determined by 24-hour urine collection or estimated by Cockcroft-Gault formula (within 21 days prior to registration)
* Negative 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 agree to use a medically effective means of birth control throughout protocol treatment
* Patient must provide study specific informed consent prior to study entry, including the mandatory pre-treatment plasma EBV DNA assay

Exclusion Criteria:

* Prior invasive malignancy (except node negative, 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; however, at least 6-weeks recovery is necessary if the last regimen included nitrosourea or mitomycin
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Patients with hearing loss assessed to be primarily sensorineural in nature, requiring a hearing aid, or intervention (i.e. interfering in a clinically significant way with activities of daily living); a conductive hearing loss that is tumor-related is allowed
* \>= Grade 2 peripheral sensory neuropathy (CTCAE, v. 4.0)
* Severe, active co-morbidity, defined as follows:

  * Major medical or psychiatric illness, which in the investigator's opinion would interfere with the completion of therapy and follow up or with full understanding of the risks and potential complications of the therapy
  * Unstable angina and/or uncontrolled congestive heart failure within past 6 months
  * Myocardial infarction within the last 6 months
  * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; note that patients switched from IV antibiotics and currently on oral antibiotics whose infection is assessed to be adequately treated or controlled are eligible
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
  * Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
* Prior allergic reaction to the study drug(s) involved in this protocol
* Patients with undetectable pre-treatment plasma EBV DNA