Concurrent high-dose intermittent cisplatin should be delivered to patients with stage IVA-IVB OPSCC receiving definitive radiotherapy.

Concurrent cetuximab or carboplatin-fluorouracil may be delivered to patients with stage IVA-IVB OPSCC receiving definitive radiotherapy who are not medically fit for high-dose cisplatin.

Concurrent weekly cisplatin may be delivered to patients with stage IVA-IVB OPSCC receiving definitive radiotherapy who are not medically fit for high-dose cisplatin, after a careful discussion of patient preferences and the limited prospective data supporting this regimen.

Concurrent cetuximab should not be delivered in combination with chemotherapy to patients with stage IVA-IVB OPSCC receiving definitive radiotherapy.

Intra-arterial chemotherapy should not be delivered to patients with stage IVA-IVB OPSCC receiving definitive radiotherapy.

Concurrent systemic therapy should be delivered to patients with T3 N0-1 OPSCC receiving definitive radiotherapy.

Concurrent systemic therapy may be delivered to patients with T1-T2 N1 OPSCC receiving definitive radiotherapy who are considered at particularly significant risk for locoregional recurrence, after a careful discussion of patient preferences and the limited evidence supporting its use.

Concurrent systemic therapy should not be delivered to patients with stage I-II OPSCC receiving definitive radiotherapy.

Concurrent high-dose intermittent cisplatin should be delivered with postoperative radiotherapy to patients with positive surgical margins and/or extracapsular nodal extension; this high-risk population includes patients independent of HPV status or the extent of extranodal tumor.

Concurrent weekly cisplatin may be delivered with postoperative radiotherapy 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.

For the high-risk postoperative patient unable to receive cisplatin-based concurrent chemoradiotherapy, radiotherapy alone should be routinely delivered without concurrent systemic therapy; given the limited evidence supporting alternative regimens, treatment with noncisplatin systemic therapy should be accompanied by a careful discussion of the risks and unknown benefits of the combination.

Patients treated with postoperative radiotherapy should not receive concurrent weekly carboplatin.

Patients treated with postoperative radiotherapy should not receive cetuximab, either alone or in combination with chemotherapy, although such regimens are currently under investigation.

Patients treated with postoperative radiotherapy should not routinely receive concurrent weekly docetaxel given the limited evidence supporting its use, although such regimens are currently under investigation.

Patients treated with postoperative radiotherapy should not receive concurrent mitomycin-C, alone or with bleomycin, given the limited evidence and experience supporting its use.

Postoperative chemotherapy should not be delivered alone or sequentially with postoperative radiotherapy.

Patients with intermediate-risk factors should not routinely receive concurrent systemic therapy with postoperative radiotherapy.

Patients with intermediate-risk factors whose surgical procedure and/or pathologic findings imply a particularly significant risk of locoregional recurrence may receive concurrent cisplatin-based chemotherapy after a careful discussion of patient preferences and the limited evidence supporting its use in this scenario; alternative systemic treatment regimens should only be used in the context of a clinical trial.

Postoperative radiotherapy should be delivered to patients with pathologic T3 or T4 disease.

Postoperative radiotherapy should be delivered to patients with pathologic N2 or N3 disease.

Postoperative radiotherapy may be delivered to patients with pathologic N1 disease without extracapsular nodal extension after a careful discussion of patient preferences and the limited evidence of outcomes following surgery alone in this scenario.

Postoperative radiotherapy may be delivered to patients with lymphovascular invasion and/or perineural invasion as the only risk factor(s) after a careful discussion of patient preferences and the limited evidence of outcomes following surgery alone in this scenario.

Postoperative radiotherapy 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, after a careful discussion of patient preferences and the potential harms and benefits of radiotherapy.

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

A dose of 70 Gy over 7 weeks should be delivered to gross primary and nodal disease in patients with stage III-IV OPSCC selected to receive standard, once-daily definitive radiotherapy.

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.

Altered fractionation should be used in patients with stage IVA-IVB OPSCC treated with definitive radiotherapy who are not receiving concurrent systemic therapy.

Either accelerated radiotherapy or hyperfractionated radiotherapy may be used in patients with OPSCC treated with altered fractionation definitive radiotherapy after a careful discussion of patient preferences and the limited evidence supporting one regimen over the other.

Either standard, once-daily radiotherapy or accelerated fractionation may be used when treating OPSCC with concurrent systemic therapy after a careful discussion of patient preferences and the risks and benefits of both approaches.

Altered fractionation should be used in patients with T3 N0-1 OPSCC treated with definitive radiotherapy who do not receive concurrent systemic therapy.

Altered fractionation may be used in patients with T1-2 N1 or T2 N0 OPSCC treated with definitive radiotherapy alone who are considered at particularly significant risk of locoregional recurrence, after a careful discussion of patient preferences and the limited evidence supporting its use in this scenario.

Adjuvant postoperative radiotherapy 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.

Adjuvant postoperative radiotherapy delivered without concurrent systemic therapy should treat regions of microscopically positive primary site surgical margins and extracapsular nodal extension at 2 Gy/fraction once daily to a total dose of 60 to 66 Gy, although there are limited data guiding this recommendation.

Adjuvant postoperative radiotherapy should be delivered to the tumor bed and involved, dissected lymph node regions at once-daily fractionation to a total dose of 56 to 60 Gy in the absence of primary site positive margins and extracapsular nodal extension.

Unilateral radiotherapy should be delivered to patients with well-lateralized (no soft palate extension or base of tongue involvement), T1-T2 tonsillar cancer, and N0-N1 nodal category.

Unilateral radiotherapy may be delivered to patients with lateralized (<1 cm of soft palate extension but without base of tongue involvement) T1-T2 N0-N2b 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.