First Generation Laryngeal Carcinoma Preservation Trials

  • The first generation of larynx preservation chemotherapy trials:
    • Appeared in the 1990s:
      • They randomized patients into surgery and radiotherapy or to induction chemotherapy cycles of cisplatin / 5FU:
        • Patients who responded to chemotherapy then received radiotherapy:
          • With possible salvage surgery
      • If they did not respond to the chemotherapy:
        • They received surgery and postoperative radiotherapy
    • Generally, the results of these studies showed:
      • No significant difference in survival:
        • Between the two treatment arms
    • The larynx was preserved in:
      • 56% of patients undergoing the experimental chemoradiotherapy arm
  • In 2000, Pignon et al:
    • Published a meta-analysis of the first generation of laryngeal preservation chemoradiotherapy trials:
      • In the main, they included T3 laryngeal and hypopharyngeal cancers
    • There was no statistically significant difference in overall survival:
      • However, it is important to note:
        • That there was a trend to benefit from surgery:
          • Hazard ratio 1.19 intervals (0.97–1.46)
        • Surgery ± radiotherapy:
          • Resulted in overall survival of 45%:
            • Compared to an overall survival from chemoradiotherapy of:
              • 39%
        • 56% of those who survived with chemoradiotherapy:
          • Managed to avoid laryngectomy:
            • Giving an overall laryngectomy survival rate of:
              • 23% at five years
        • Patients treated with chemoradiotherapy:
          • Had almost double the local recurrence rate:
            • But less distant metastases than the patients treated with surgery
        • Analysis of laryngeal cancer patients separately from hypopharyngeal cancer patients:
          • Showed that laryngeal cancer patients in the surgical arm:
            • Demonstrated a risk reduction of 32%:
            • This suggests that advanced laryngeal tumors would be better treated with surgery than chemoradiotherapy:
              • On the other hand, hypopharyngeal cancer patients showed no difference in survival between the two modalities of treatment
  • The meta-analysis showed that the overall survival benefit from chemotherapy in addition to radiotherapy:
    • Was 4% at five years
  • Concomitant chemotherapy:
    • Resulted in an 8% overall survival benefit:
      • Compared to a 4% overall survival benefit from neoadjuvant chemoradiotherapy
  • Adjuvant chemoradiotherapy:
    • Resulted in no overall survival benefit
  • These findings have resulted in the adoption of concomitant chemoradiotherapy as the standard regimen for delivery of chemotherapy when treating laryngeal and pharyngeal cancers:
    • Recently, an update of this meta-analysis confirmed an overall survival effect of 6.5% for concomitant chemoradiotherapy
  • References:
    • The Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. New England Journal of Medicine 1991; 324: 1685–90.
    • Pignon JP, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 2000; 355: 949–55.
    • Pignon JP, le Maítre A, Maillard E et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiotherapy and Oncology 2009; 92: 4–14.
    • Forastiere AA, Goepfert H, Maor M et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. New England Journal of Medicine 2003; 349: 2091–8.
#Arrangoiz #CancerSurgeon #HeadandNeckSurgeon #SurgicalOncologist #MountSinaiMedicalCenter #MSMC #Miami #Mexico #LaryngealCancer

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