What is the recommended dose and fractionation schedule of radiotherapy for a patient with head and neck cancer, good performance status, and no significant medical comorbidities?

Radiotherapy Dosing for Head and Neck Cancer

For a patient with head and neck cancer, good performance status, and no significant comorbidities, deliver 70 Gy in 35 fractions (2 Gy per fraction) over 7 weeks to gross disease when using standard fractionation with concurrent chemotherapy, or use altered fractionation (hyperfractionation or acceleration) if treating with radiotherapy alone in advanced disease. 1

Definitive Radiotherapy Dose Recommendations

For Gross Disease (Primary Tumor and Involved Nodes)

• Standard fractionation: 70 Gy delivered at 2 Gy per fraction over 7 weeks to all gross primary and nodal disease in stage III-IV head and neck cancer 1
• The NCCN guidelines specify a range of 66-74 Gy at 2.0 Gy/fraction for primary tumor and gross adenopathy 1
• Do not exceed 75 Gy using conventional 2.0 Gy fractionation, as doses above this threshold lead to unacceptable rates of normal tissue injury 1

For Elective Nodal Regions (Microscopic Disease Risk)

• Deliver approximately 50 Gy in 2 Gy fractions (or biologically equivalent dose slightly higher) to clinically and radiographically negative regions at risk for microscopic spread 1
• The NCCN specifies 44-64 Gy for elective nodal irradiation, depending on estimated tumor burden and fraction size 1

Fractionation Strategy Selection

When Using Concurrent Chemotherapy

• Either standard once-daily radiotherapy (70 Gy in 35 fractions) OR accelerated fractionation may be used after discussing patient preferences and the risks/benefits of both approaches 1
• The Danish Head and Neck Cancer Group trial defined accelerated radiotherapy as 66-68 Gy delivered at six fractions per week (instead of five), completing treatment in 6 weeks rather than 7 weeks 1

When NOT Using Concurrent Chemotherapy

Altered fractionation is strongly recommended for:

• Stage IVA-IVB disease treated with definitive radiotherapy alone 1
• T3 N0-1 oropharyngeal cancer treated without concurrent systemic therapy 1

Two altered fractionation options:

1. Hyperfractionation: 1.15 Gy twice daily to 80.5 Gy total over 7 weeks (equivalent to approximately 70 Gy₂) 1, 2

   • The EORTC 22791 trial demonstrated superior local control (56% vs 38% at 5 years, P=.01) compared to conventional fractionation without increased late complications 1

2. Accelerated fractionation: Same total dose (66-68 Gy) delivered over shorter time (6 weeks instead of 7) 1

• Either approach may be selected after careful discussion of patient preferences, as limited evidence supports one regimen over the other 1
• Schedules delivering at least 1000 cGy/week are recommended to counteract accelerated repopulation of squamous cell carcinomas 1

Postoperative Radiotherapy Dosing

High-Risk Features (Positive Margins or Extracapsular Extension)

• Deliver 60-66 Gy at 2 Gy/fraction once daily to regions with microscopically positive surgical margins or extracapsular nodal extension 1
• Higher doses (60-66 Gy) with or without chemotherapy are specifically recommended for these high-risk features 1

Intermediate-Risk Features

• Postoperative radiotherapy is recommended for advanced T stage, depth of invasion, multiple positive nodes (without extracapsular spread), or perineural/lymphatic/vascular invasion 1
• Standard postoperative doses apply, though specific dosing for intermediate-risk features is less well-defined in guidelines 1

Timing Considerations

• Begin postoperative radiotherapy within 6 weeks or less after resection 1

Site-Specific Considerations

Nasopharyngeal Cancer

• T1 N0 M0 tumors: 66-70 Gy with standard fractionation achieves 80-90% local control 1
• Locally advanced disease: Concurrent platinum-based chemotherapy with radiotherapy followed by adjuvant cisplatin/5-FU is standard 1

Early-Stage Disease (T1-2 N0-1)

• Altered fractionation may be considered for T1-2 N1 or T2 N0 oropharyngeal cancer at particularly significant risk of locoregional recurrence, after careful discussion of patient preferences 1

Critical Pitfalls to Avoid

• Do not use induction chemotherapy routinely for oropharyngeal squamous cell carcinoma, as it has not proven additional benefit and represents a strong recommendation against its routine use 1
• Avoid exceeding 75 Gy with conventional fractionation due to unacceptable normal tissue injury rates 1
• When using IMRT (now the predominant technique at major cancer centers), be aware that in-field recurrences can still occur despite improved toxicity profiles 1
• Ensure adequate weekly dose delivery (≥1000 cGy/week) when using radiotherapy alone to prevent tumor repopulation 1

Technical Delivery

• IMRT is widely used and reduces long-term toxicity to salivary glands, temporal lobes, mandible, auditory structures, and optic structures in oropharyngeal and nasopharyngeal cancers 1
• Overall survival remains similar between IMRT and conventional RT, though toxicity profiles favor IMRT 1
• Dose to different risk volumes can be delivered sequentially (shrinking field technique) or simultaneously using twice-daily schemes 1