What are the treatment options for head and neck cancer?

Head and Neck Cancer Treatment

Treatment Selection by Disease Stage

For early-stage head and neck cancer (Stage I-II), either surgery or radiotherapy alone provides equivalent locoregional control with 5-year overall survival rates of 70-90%, and the choice should be based on anticipated functional outcomes. 1, 2

Early-Stage Disease (Stage I-II)

• Surgery or radiotherapy alone are equally effective standard options for T1-2, N0 tumors, with treatment selection based on tumor location and expected functional impact 1
• For glottic carcinomas specifically, radiotherapy is the treatment of choice for T2N0 disease 1
• Modern radiotherapy should utilize 3D conformal radiation therapy and/or intensity-modulated radiation therapy (IMRT) 1
• Standard conventional fractionation is preferred when radiotherapy is used definitively for T1-2, N0 tumors 1

Locally Advanced Resectable Disease (Stage III-IVa)

Concurrent cisplatin-based chemoradiation is the standard category 1 treatment for locally advanced disease in patients with good performance status (PS 0-1), using high-dose cisplatin 100 mg/m² every 3 weeks with conventional fractionation radiotherapy (70 Gy in 7 weeks). 3, 4

Primary Treatment Options:

• Concurrent chemoradiation with cisplatin is superior to radiotherapy alone for response rate, disease-free survival, and overall survival, achieving 5-year survival rates of 25-60% (>80% for HPV-associated oropharynx cancer) 1, 2
• Surgery with neck dissection followed by postoperative chemoradiation with single-agent platinum is indicated for patients with high-risk features (extracapsular extension and/or R1 resection) 1, 4
• Radiotherapy with cetuximab (category 1) is an alternative for patients not medically fit for cisplatin-based chemoradiation, demonstrating higher response rates, longer disease-free progression, and longer overall survival versus radiotherapy alone 1, 4

Alternative Concurrent Regimens:

• Carboplatin/5-FU (category 1) 4
• Weekly low-dose cisplatin, weekly taxanes, or combinations are inadequately studied for specific recommendation 1

Induction Chemotherapy Consideration:

• TPF regimen (docetaxel + cisplatin + 5-fluorouracil) is FDA-approved for induction treatment of locally advanced squamous cell carcinoma of the head and neck 5
• TPF shows superior response rates, disease-free survival, and overall survival compared to the older cisplatin/5-FU doublet 3, 4
• Induction chemotherapy remains category 3 with significant controversy regarding its role compared to concurrent chemoradiation alone, and should be reserved for patients with PS 0-1 seeking organ preservation 3
• For advanced larynx and hypopharynx cancer requiring total laryngectomy, neoadjuvant chemotherapy followed by radiotherapy allows organ preservation, though it has no impact on disease-free or overall survival 1

Unresectable Disease (T4b)

Concurrent chemoradiation is the standard treatment for unresectable tumors, with platinum-based regimens remaining the standard chemotherapy. 1

• For patients with poor performance status (PS 2-3), standard radiotherapy alone should be considered due to increased toxicity risks with combined modality treatment 1, 3

Recurrent/Metastatic Disease

First-line treatment for incurable locoregional recurrences or distant metastatic disease is pembrolizumab (programmed death ligand-1 inhibitor) alone or in combination with platinum-doublet chemotherapy, achieving median survival of 12-15 months. 2

Chemotherapy Options:

• Cisplatin or carboplatin + 5-FU + cetuximab (category 1 for non-nasopharyngeal cancer) improves median survival to 10.1 months versus 7.4 months with platinum/5-FU alone 3, 4
• Cisplatin or carboplatin + taxane (docetaxel or paclitaxel) is an alternative combination 3, 4
• Weekly methotrexate is considered standard palliative treatment for patients with poor performance status 1, 4
• Combination chemotherapy produces higher response rates than single-agent methotrexate but without demonstrated survival benefit 1, 4

Nasopharyngeal Cancer

• T1, N0, M0 nasopharyngeal tumors may be treated with definitive radiotherapy alone 1
• Concurrent radiotherapy with cisplatin is standard for locally advanced nasopharyngeal tumors, showing improved survival compared to radiotherapy alone 1

Essential Treatment Principles

Multidisciplinary Approach

• A multidisciplinary treatment team must establish the treatment plan in all cases 1, 6, 2
• The complexity of disease requires coordination among surgeons, radiation oncologists, medical oncologists, and supportive care specialists 6, 7

Supportive Care Requirements

• Nutritional status must be corrected and maintained throughout treatment 1, 4
• Dental rehabilitation is mandatory prior to radiotherapy to prevent complications 1, 4
• Evaluation of thyroid function in patients with neck irradiation is recommended at 1,2, and 5 years post-treatment 1, 4

Workup and Staging

• Complete staging includes physical examination, head and neck endoscopy, and CT scan or MRI 1
• Thoracic CT scan should be performed to rule out metastatic disease 1
• FDG-PET at staging is under investigation 1
• Routine esophagoscopy and bronchoscopy are not recommended 1

Follow-Up Protocol

• Clinical examination every 3 months for 2 years, then every 6 months for years 3-5, then annually 1
• Imaging should be performed as clinically indicated for suspected recurrence 1
• The aim is early detection of locoregional recurrence and potentially curable second primary tumors 1

Critical Caveats

Toxicity Considerations

• All combined chemoradiotherapy regimens are associated with significant mucosal toxicities requiring close monitoring by an experienced team 4
• Acute toxicity of combined chemotherapy and radiation is significant, though acute side effects usually resolve after treatment 8
• Xerostomia is the major long-term complication affecting patients undergoing radiation or chemoradiation 8
• Speech disorder, dysphagia, pain, and depression are common side effects affecting quality of life regardless of treatment modality 8

Treatment Selection Pitfalls

• Avoid combined modality therapy when possible in certain settings, as it increases complication rates without improving survival compared to either modality alone 9
• Adjuvant chemotherapy alone (without radiation) has demonstrated no benefit 1
• Neoadjuvant chemotherapy has demonstrated no effect on disease-free survival or overall survival when not followed by appropriate definitive treatment 1
• Performance status is essential for treatment selection—PS 0-1 is required for intensive regimens like TPF or high-dose cisplatin 3, 4

Organ Preservation

• Despite significant acute toxicity, organ preservation with chemoradiation may improve quality of life compared to surgery and postoperative radiation 8
• Treatment goals must balance cure, organ preservation, function preservation, and quality of life 6, 7
• Choice of treatment for locoregionally advanced disease should involve shared decision-making and consideration of effects on speech, swallow function, and appearance 2