Treatment De-Intensification for Squamous Cell Carcinoma of the Oropharynx

• Grade 3+ late toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  To achieve prevalence of grade 3+ late toxicity at 2 years < 15% while maintaining a locoregional tumor control > 85 + or - 7% at the same time interval (toxicity is scored at 5.11 and 9.5 and locoregional and locoregional control at 9.4).
• Quality of Life [ Time Frame: Pretreatment, 8 weeks, 3 months, then every 3 months fo rthe first 2 years, then every 6 months for years 3-5 and finally annually ] [ Designated as safety issue: No ]
  To determine the quality of life of surviving patients (5.11 and 9.5)
• Adverse events and their cause [ Time Frame: Pretreatment, 3 months, then every 3 months for the first 2 years, then every 6 months for years 3-5 and finally annually ] [ Designated as safety issue: Yes ]
  To determine the nature and prevalence of side effects at different time intervals and describe their relationship to pretreatment function and local dose and treated volume.

The purpose of this study is to examine disease control of contemporary oropharyngeal cancer.

As for many other primary subsites of the head and neck district, two main options have been traditionally employed for the treatment of squamous cell carcinoma of the oropharynx (ORO-SCC), surgery and radiotherapy (RT). The latter has been shown to be less 'invasive' and morbid than radical surgery and therefore has gained consensus as first line option in ORO-SCC at many Institutions across the country.

Surveillance Epidemiology and End Results (SEER) data from 1975 to 2002 show an approximate 5% to 8% improvement in 5-year overall survival for squamous head and neck cancer. Most of this improvement occurred in oropharyngeal carcinoma. Table 1 summarizes results from contemporary series using non-surgical-based approach for ORO-SCC. They consistently show that long-term locoregional control rates are in the order of 80-95%.

• Radiation: IMRT
  70 Gy, 63 Gy and 58.1 Gy to primary tumor and whole neck (PTV1-3) in 35 fractions. The Px to each PTV is reported in table 6. Now we have 4 dose levels, 70, 63, 58.1 and 50.75 Gy. In cases after primary tumor surgery where there is no residual macroscopic disease left, the total dose to PTV1 can be reduced from 70 Gy to 68.25 Gy. In this case PTV68.25 is treated as PTV70 regarding overlap with the various OAR's.
• Drug: Cisplatin
  The first dose of cisplatin 40mg/m2 IV will be administered within the first 3 days of the start of RT and repeated weekly for the duration of RT. If RT is held, cisplatin will also be held.
• Drug: Carboplatin
  6.2.4 Switch to Carboplatin: In case of any of the followings, cisplatin will be substituted to carboplatin: serum creatinine above the upper limit of normal and creatinine clearance < 60; refractory magnesium and electrolyte wasting; ototoxicity; peripheral neuropathy grade 2. Weekly carboplatin dosing would be at AUC = 2; q 3wk dosing at AUC = 5.

Inclusion Criteria:

• Biopsy-proven SCC of the oropharynx (tonsil, base of tongue, pharyngeal wall or palate).
• Tumor positive for infection with HPV virus type 16 or other types (section 8.0).
• T stage: 1, 2. T3 tumors are allowed if the tumor is arising from the tonsillar fossa and/or is exophytic based on both clinical exam and CT; Surgery of the primary tumor is limited to incisional or excisional biopsies (i.e tonsillectomy) even without macroscopic disease left. Positive resection margins and/or gross residual disease at the primary site are allowed.
• Any N stage, but resectable; lymph nodes in both sides of the neck are at risk of metastatic disease, according to clinical judgment, and require irradiation; pre-treatment surgery in the neck in the forms of incisional/excisional biopsy or a multilevel neck dissection is allowed only if there is gross tumor left at the primary site.
• No other malignancy except for non-melomatous skin cancer, early stage prostate cancer (T<2a and PSA<10 and GLS<7) or a carcinoma not of head and neck origin disease free for > 5 yrs.
• Cannot have distant metastasis (M0)
• ECOG performance status 0-1.
• Patient's nutritional and general physical condition must be considered compatible with the proposed radiotherapeutic treatment.
• Patient is judged to be mentally reliable to follow instructions and to keep appointments.
• Patient is on no other treatment for head and neck cancer.
• Signed study-specific informed consent prior to registration.

Exclusion Criteria:

• Evidence of distant metastases.
• Absence of macroscopic disease after upfront surgery, i.e., TxNx and TxN0. TxN+ and T1-3Nx are eligible if the T/N stage categories meet the criteria of 3.1.1.
• Previous irradiation for head and neck tumor; concurrent chemotherapy other than the treatment per protocol; previous chemotherapy ≤ 3 months from start of RT.
• Active untreated infection.
• Major medical or psychiatric illness, which in the investigators' opinions would interfere with either completion of therapy and follow-up or with full and complete understanding of the risks and potential complications of the therapy.
• Prophylactic use of amifostine or pilocarpine is not allowed.