Management of Localized or Locally Advanced Oropharyngeal Squamous Cell Carcinoma – ASTRO Clinical Practice Guideline

SUMMARY: The American Cancer Society estimates that 49,670 people will be diagnosed with Oral cavity and Oropharyngeal cancer in 2017 and an estimated 9700 patients will die of the disease. Over 90% of these malignancies are Squamous Cell Carcinomas (SCCs). OroPharyngeal Squamous Cell Carcinoma (OPSCC) involves the tonsils and base of the tongue, and recent studies have shown that over 70% of these tumors are caused by Human Papilloma Virus (HPV) and HPV-16 is the predominant type present in the tumor cells. The CDC estimates that more than 2,370 new cases of Human Papilloma Virus associated OPSCC are diagnosed in women and nearly 9,356 are diagnosed in men, each year in the United States, and this incidence has been on the rise.

The American Society for Radiation Oncology (ASTRO) convened the OroPharyngeal Squamous Cell Carcinoma (OPSCC) Guideline Panel which consisted of a multidisciplinary team of radiation, medical, and surgical oncologists, to perform a systematic literature review of studies published from January 1990 through December 2014, in an attempt to present evidence-based guidelines, for the treatment of OPSCC, with definitive or adjuvant Radiation Therapy (RT).

The following are the key questions and recommendations of the Guideline panel.

(1) When is it appropriate to add systemic therapy to definitive RT in the treatment of OPSCC?

Stage IVA-B disease

A) Patients with stage IVA-B tumors receiving definitive RT should receive concurrent high-dose intermittent Cisplatin.

B) Patients who are medically unfit for high-dose Cisplatin should receive concurrent Cetuximab or Carboplatin-Fluorouracil.

C) Weekly Cisplatin may be considered for patients who are medically unfit for high-dose Cisplatin.

D) Concurrent Cetuximab should not be administered in combination with chemotherapy.

E) Intra-arterial chemotherapy should not be used in this patient group.

Stage III disease

A) Patients with T3 N0-1 tumors should receive concurrent systemic therapy.

B) Patients with T1-T2 N1 tumors who are at a significant risk for locoregional recurrence may be considered for concurrent systemic therapy.

Stage I to II disease

Concurrent systemic therapy is not recommended for this patient group as there is no evidence supporting the use of systemic therapy in this generally favorable population.

(2) When is it appropriate to deliver PostOperative RT (PORT) with and without systemic therapy following primary surgery for OPSCC?

A) Concurrent high-dose intermittent Cisplatin should be delivered with PORT to patients with positive surgical margins and/or extracapsular nodal extension, independent of HPV status or the extent of extranodal tumor.

B) Concurrent weekly Cisplatin may be administered with PORT to patients who are considered inappropriate for standard high-dose intermittent Cisplatin, after a careful discussion of patient preferences and the limited evidence supporting this treatment schedule.

C) For the high-risk postoperative patient unable to receive Cisplatin-based concurrent chemoradiation therapy, RT alone should be routinely delivered without concurrent systemic therapy. Given the limited evidence supporting alternative regimens, treatment with non-Cisplatin systemic therapy should be accompanied by a careful discussion of the risks and unknown benefits of the combination.

D) Patients treated with PORT should not receive concurrent weekly Carboplatin, weekly Docetaxel or Cetuximab, either alone or in combination with chemotherapy, although such regimens are currently under investigation.

E) Patients treated with PORT should not receive concurrent Mitomycin-C, alone or with Bleomycin, given the limited evidence and experience supporting its use.

F) Postoperative chemotherapy should not be delivered alone or sequentially with postoperative RT.

Intermediate-risk pathologic factors such as lymphovascular invasion (LVI), perineural invasion (PNI), T3-4 disease, or positive lymph nodes

A) These patients should not routinely receive concurrent systemic therapy with PORT.

B) Concurrent Cisplatin-based chemotherapy may be considered if the post operative pathologic findings suggest significant risk of locoregional recurrence.

C) PORT should be delivered to patients with pathologic T3 or T4 and pathologic N2 or N3 disease.

D) PORT may be delivered to patients with pathologic N1 disease after a careful discussion with the patient.

E) PORT may be delivered to patients with LVI and/or PNI as the only risk factor(s), after a careful discussion with the patient.

No pathologic risk factors

PORT may be delivered to patients without conventional adverse pathologic risk factors only if the clinical and surgical findings imply a particularly significant risk of locoregional recurrence and after a careful discussion with the patient.

(3) When is it appropriate to use induction chemotherapy in the treatment of OPSCC?

Induction Chemotherapy should not be routinely delivered to patients with OPSCC.

(4) What are the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC?

A) For patients with stage III-IV disease a dose of 70 Gy over 7 weeks should be delivered to gross primary and nodal disease.

B) The biologically equivalent dose of approximately 50 Gy in 2 Gy fractions or slightly higher should be delivered electively to clinically and radiographically negative regions at-risk for microscopic spread of tumor.

C) Altered fractionation should be used in patients with stage IVA-B disease treated with definitive RT, who are not receiving concurrent systemic therapy as well as patients with T3 N0–1 disease not receiving concurrent chemoradiation. Additionally, it may be considered for patients with T1–2 N1 or T2 N0 disease at high risk for recurrence.

D) When treating OPSCC with concurrent systemic therapy,, either standard or accelerated fractionation may be implemented.

Adjuvant PORT

Adjuvant PORT should be delivered to regions of microscopically positive primary site surgical margins and extracapsular nodal extension at 2 Gy/fraction once daily to a total dose between 60 and 66 Gy.

Early T-stage tonsillar carcinoma

A) Unilateral RT should be delivered to patients with well-lateralized (confined to tonsillar fossa) T1-T2 tonsillar cancer and N0-N1 nodal category.

B) Unilateral RT may be delivered to patients with lateralized (<1 cm of soft palate extension but without base of tongue involvement) T1-T2 N0-N2a tonsillar cancer, without clinical or radiographic evidence of extracapsular extension, after careful discussion of patient preferences and the relative benefits of unilateral treatment versus the potential for contralateral nodal recurrence and subsequent salvage treatment.

Radiation therapy for oropharyngeal squamous cell carcinoma: Executive summary of an ASTRO Evidence-Based Clinical Practice Guideline. Sher DJ, Adelstein DJ, Bajaj GK, et al. DOI: