RTOG 91-11: Landmark Organ-Preservation Trial in Advanced Laryngeal Cancer

Design and Arms:
- Population:
  - 547 patients with stage III to IV (cT2 bulky to cT4) resectable squamous cell carcinoma of the larynx(supraglottic or glottic):
    - Who were candidates for total laryngectomy
Randomization (3 arms):
- Induction PF → RT (Control):
  - Three cycles cisplatin 100 mg / m² day 1 + 5-FU 1 g/m²/day × 5, followed by definitive RT (66 to 76 Gy) for responders
- Concurrent CRT:
  - RT (70 Gy) + cisplatin 100 mg / m² q3wk ×3
- RT Alone:
  - 70 Gy definitive radiation
Primary endpoint:
- Laryngectomy-free survival (LFS) and larynx preservation without loss of overall survival (OS)

Interpretation:
- Concurrent cisplatin-RT produced the highest larynx-preservation rate and superior laryngectomy-free survival compared with both RT alone and induction PF
- No OS advantage for any arm:
  - Survival curves overlapped
Long-Term and Late Toxicities (Forastiere et al., JCO 2013 update):
- Non–cancer deaths:
  - Cardiopulmonary, treatment-related:
    - More frequent in the concurrent CRT arm after year 5
- Late swallowing dysfunction and chronic aspiration:
  - Higher with CRT
- Highlights need for lifelong surveillance and aggressive supportive care:
  - Speech / swallow therapy
  - Pulmonary monitoring
Clinical Application:
- Standard of care for organ preservation:
  - Definitive RT + high-dose cisplatin (100 mg / m² q3wk ×3):
    - For patients who are surgical candidates but wish to avoid total laryngectomy and are cisplatin-eligible
    - Requires baseline audiogram, renal function, and performance status assessment
- Alternatives:
  - For cisplatin-ineligible patients:
    - Cetuximab-RT or carboplatin-based CRT:
      - With the understanding of lower organ-preservation rates

Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO