What are the treatment options for head and neck squamous cell carcinoma?

Treatment Options for Head and Neck Squamous Cell Carcinoma

The treatment of head and neck squamous cell carcinoma (SCCHN) requires a multidisciplinary approach with specific regimens based on tumor resectability, stage, and location, with chemoradiotherapy being the standard of care for unresectable tumors and surgery with adjuvant therapy for resectable disease. 1

Staging and Initial Assessment

• Routine staging includes:

  • Physical examination
  • Head and neck endoscopy
  • Head and neck CT scan or MRI
  • Thoracic CT scan (to rule out metastatic disease)

• TNM staging system is used with T4 tumors subdivided into:

  • T4a (resectable)
  • T4b (unresectable)
  • Stage IV is further subdivided into IVa, IVb, and IVc (metastatic disease) 1

Treatment Algorithm by Resectability Status

Resectable Tumors

1. Early Stage (I-II):

   • Either surgery or radiotherapy (external or brachytherapy) provides similar locoregional control 1
   • For glottic carcinomas, radiotherapy may be used instead of surgery with curative intent 1

2. Advanced Resectable Tumors (III, IVa):

   • Surgery plus postoperative radiotherapy
   • For high-risk features (extracapsular extension and R1 resection): postoperative chemoradiotherapy with single-agent platinum 1
   • Adjuvant chemoradiotherapy with single-agent platinum following surgery increases disease-free and overall survival 1

3. Organ Preservation Strategy:

   • For advanced larynx and hypopharynx cancer requiring total laryngectomy:
     • Neoadjuvant chemotherapy (cisplatin with 5-fluorouracil) followed by radiotherapy allows for organ preservation 1
     • Note: This approach has no impact on disease-free or overall survival 1
     • Concurrent chemoradiotherapy has shown higher larynx preservation rates in some trials 1

Unresectable Tumors

1. Standard Approach:

   • Chemoradiotherapy (concomitant or alternated) is strongly recommended 1
   • This approach is superior to radiotherapy alone for response rate, disease-free and overall survival 1
   • Platinum-based regimens remain the standard chemotherapy for concurrent chemoradiotherapy 1
   • Radiotherapy given concomitantly with cetuximab has demonstrated survival benefit versus radiotherapy alone 1

2. For Poor Performance Status Patients:

   • Standard radiotherapy alone should be considered 1

3. Emerging Approach:

   • Induction chemotherapy with cisplatin/5-fluorouracil/docetaxel followed by radiotherapy alone or chemoradiotherapy leads to higher response rates, longer disease-free progression and longer overall survival versus cisplatin/5-fluorouracil regimen 1

Recurrent/Metastatic Disease

1. Localized Recurrence:

   • Surgery (if operable) or re-irradiation can be considered 1

2. Widespread Recurrence/Metastatic Disease:

   • Palliative chemotherapy is the standard option 1
   • Weekly methotrexate may be considered as the accepted treatment 1
   • Combination chemotherapy (cisplatin, 5-fluorouracil or taxanes) produces higher response rates than single-agent methotrexate, but no survival benefit has been demonstrated 1
   • Nivolumab (anti-PD-1 antibody) is FDA-approved for adult patients with recurrent or metastatic SCCHN with disease progression on or after platinum-based therapy 2, 3

Important Treatment Considerations

1. Multidisciplinary Approach:

   • Treatment schedule should be established by a multidisciplinary team 1

2. Supportive Care:

   • Patient's nutritional status must be corrected and maintained 1
   • Dental rehabilitation is indicated before radiotherapy 1

3. Follow-up Protocol:

   • Treatment response should be evaluated by clinical examination and CT scan or MRI 1
   • Physical examination and radiologic imaging should be included in routine follow-up 1
   • Evaluation of thyroid function in patients with irradiation to the neck is recommended at 1,2, and 5 years 1

Emerging Therapies

• Immune checkpoint inhibitors (ICIs) have shown promising results in second-line treatment of recurrent/metastatic SCCHN 4, 3
• Targeted therapies, including epidermal growth factor receptor antagonists, are showing promise in both locoregionally advanced and recurrent/metastatic SCCHN 5
• Ongoing clinical trials are investigating novel approaches including combination immunotherapies, antibody-drug conjugates, and cellular therapies 6

Common Pitfalls and Caveats

• Induction chemotherapy alone has demonstrated no benefit in disease-free survival or overall survival in most trials 1
• Adjuvant chemotherapy alone (without radiation) has demonstrated no benefit 1
• Increased toxicity is associated with chemoradiotherapy compared to radiotherapy alone 1
• The optimal approach to post-treatment surveillance remains controversial 1