Adjuvant Chemoradiotherapy for Head and Neck Squamous Cell Carcinoma

  • In many scenarios, single-modality radiation therapy:
    • Is a historical standard intervention after primary surgery for stages III and IV head and neck cancer
  • Intergroup study 0034 (RTOG 8503):
    • Which randomly assigned patients with resected head and neck squamous cell carcinoma to receive:
      • Postoperative radiation therapy alone or postoperative cisplatin (100 mg/m2 once every 3 weeks) plus 5-FU (1000 mg/m2/day in a continuous infusion for 120 hours every 3 weeks) followed by radiotherapy:
        • Failed to show significant differences in outcomes between the two treatment groups
    • A retrospective analysis did identify subsets of patients with high-risk features on surgical pathology:
      • The study suggested that clinical studies of postoperative concurrent chemo-radiation should be conducted for patients with high-risk disease
  • Bachaud and colleagues conducted a randomized trial for patients who had undergone primary surgery for head and neck cancer and had high-risk disease:
    • Defined as extracapsular spread of malignancy in resected lymph nodes (Figure)
    • Eighty-three patients were randomly assigned to receive post- operative radiotherapy alone or postoperative radiotherapy with concurrent cisplatin (50 mg administered intravenously once a week in a flat dose)
      • Overall survival and disease-free survival were significantly better:
        • In the combined modality group:
          • OS: 36% vs 13% (p < 0.01)
          • DFS: 45% vs 23% (p < 0.01)
      • The improvement in the locoregional control rate approached statistical significance in favor of the combined modality group:
        • 77% vs 59% (p = 0.08)
Design and results of a trial of postoperative concurrent chemoradiation for locally advanced head and neck carcinoma. (Adapted from Bachaud JM, Cohen-Jonathan E, Alzieu C, et al. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys 1996;36:999–1004.)
  • Cisplatin plus radiotherapy in the postoperative setting was evaluated in the:
    • EORTC 22931 and RTOG 95–01 randomized clinical trials (Figure)
Design and results of European Organization for Research and Treatment of Cancer trial 22931. HNSCC, Head and neck squamous cell carcinoma. (Adapted from Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945–1952.)
Design and results of Radiation Therapy Oncology Group trial 95–01. HNSCC, Head and neck squamous cell carcinoma. (Adapted from Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937–1944.)
  • Both studies were limited to patients who had high-risk features in the surgical pathology, although the studies differed slightly in the high-risk features that were used for eligibility:
    • In EORTC 22931:
      • High risk was defined as:
        • Positive or close surgical margins (≤ 5 mm)
        • Extra-capsular extension of nodal disease
        • Involvement of lymph nodes at level IV or V:
          • From oral cavity or oropharynx primary sites
        • Perineural disease
        • Vascular embolism
    • RTOG 95–01 defined high risk as:
      • Positive surgical margins
      • Extracapsular extension
      • Involvement of two or more lymph nodes
  • In both studies, patients were randomly assigned to radiation alone or radiation plus concurrent cisplatin (100 mg/m2 on days 1, 22, and 43)
  • The estimated 5-year overall survival:
    • From the EORTC 22931 trial was:
      • 53% in the combined modality group and 40% in the radiotherapy group (p < .05)
    • In the EORTC 22931 trial:
      • Progression-free survival and locoregional control:
        • Also were significantly improved in the combined modality group
    • With a median follow-up of 45.9 months, RTOG 95–01:
      • Demonstrated significant improvements in locoregional control and disease-free survival for the cisplatin plus radiation group:
        • But the improvement in overall survival for this group did not reach statistical significance
  • Bernier and colleagues performed a pooled analysis to compare eligibility criteria and outcomes in the two trials:
    • When the analysis was restricted to patients with high-risk disease according to criteria that were used in both studies (positive surgical margin and/or extracapsular extension):
      • A significant improvement in overall survival was seen for the group of patients that received concurrent cisplatin and radiation therapy (Figure)
      • As such, postoperative radiation plus concurrent administration of high- dose cisplatin:
        • Is a widely accepted standard of care for fit patients with either of these high-risk features on surgical pathology
Impact of adjuvant chemoradiation on survival in the presence of extracapsular extension and/or positive surgical margins in the European Organization for Research and Treatment of Cancer 22931 and Radiation Therapy Oncology Group trials 95-01. RCT, Radiochemotherapy; RT, radiotherapy. (Adapted from Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of EORTC (#22931) and RTOG (#9501).
#Arrangoiz #CancerSurgeon #HeadandNeckSurgeon #SurgicalOncologist #MountSinaiMedicalCenter #MSMC #Miami #Mexico #ChemoradiationTherapy

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s