Image-Guided Stereotactic Radiosurgery (SRS) Boost for HPV-Oropharyngeal Cancer
Image-Guided Stereotactic Radiosurgery (SRS) Boost for HPV-Oropharyngeal Cancer
This is a Phase I study looking to evaluate the safety of dose escalated stereotactic
 radiotherapy (SRS) without exceeding the maximum tolerated dose in patients with high-risk
 human papilloma virus (HPV)- unassociated oropharyngeal squamous cancer.
Human Papilloma Virus (HPV) is frequently found within tumor cells removed from patients
 diagnosed with oropharynx cancer. Tumors which do not contain HPV virus (termed
 "HPV-Negative") are not cured as frequently by radiation therapy. Tumors which do contain HPV
 in patients who have a history of cigarette smoking also are not cured as frequently by
 radiation.

 One way to potentially overcome this challenge is to deliver a more intense dose of radiation
 treatment to the tumor. The standard way to deliver radiation, termed Intensity Modulated
 Radiotherapy (IMRT), can protect normal tissues near tumors to a certain degree but not
 completely. Stereotactic radiosurgery (SRS) is a technique which can deliver radiation more
 precisely.

 This trial will test the safety of treating HPV-unassociated oropharynx tumors to higher
 radiation doses wth SRS (termed a "boost") after a standard course of IMRT has been given. In
 addition, the investigators will look at whether magnetic resonance imaging (MRI) scanning
 can detect treatment response in oropharynx tumors earlier than with standard tests.
Inclusion Criteria:

 -  Patients older than 18 years of age with histologically proven squamous cell carcinoma
 of the oropharynx

 -  HPV-negative disease status by routine p16 immunohistochemical (IHC) staining or in
 situ hybridization (ISH) of biopsied tumor tissue or >10 pack-year cigarette smoking
 history

 -  Stage T1-4, N0-3 disease, as defined by American Joint Committee on Cancer (AJCC)
 criteria

 -  Eastern Cooperative Oncology Group (ECOG) (Zubrod) Performance Status 0-2.

 Exclusion Criteria:

 -  Patients who have undergone resection of primary disease

 -  Patients who have received induction chemotherapy for their oropharynx cancer
 diagnosis

 -  Prior cancer diagnosis within 5 years, except appropriately treated localized
 epithelial skin cancer or cervical cancer

 -  Prior radiation therapy to the head and neck region

 -  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 months]) and male participants 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

 -  Patient unable to tolerate MRI or having an estimated Glomerular Filtration Rate (GFR)
 <60 ml/min/1.73 m2.

 -  Severe, active co-morbidity, defined as follows:

 -  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; note,
 however, that laboratory tests for liver function and coagulation parameters are not
 required for entry into this protocol

 -  Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease
 Control (CDC) definition; note, however, that 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

 -  History or treatment with potent immunosuppressive drugs for such conditions as organ
 transplant, severe rheumatoid arthritis, etc. within the past 6 months.