Randomized trial comparing two methods of re-irradiation after salvage surgery in head and neck squamous cell carcinoma: Once daily split-course radiotherapy with concomitant chemotherapy or twice daily radiotherapy with cetuximab

Radiother Oncol. 2018 Sep;128(3):467-471. doi: 10.1016/j.radonc.2018.05.005. Epub 2018 May 18.


Background: A previous randomized trial in recurrent Head and Neck squamous-cell carcinoma (HNSCC) has shown re-irradiation combined with chemotherapy after salvage surgery significantly improved disease-free survival (DFS). The objective of this randomized trial was to compare two methods of re-irradiation in terms of toxicity and survival.

Patients and methods: Patients with recurrence/second primary in previously irradiated area were randomly allocated to receive either 60 Gy over 11 weeks with concomitant 5FU - hydroxyurea (VP-arm), or 60 Gy (1.2 Gy twice daily) over 5 weeks with cetuximab (HFR-arm). Primary endpoint was treatment interruption >15 days (acute toxicity).

Results: Twenty-six patients were included in VP-arm and 27 in HFR-arm. One patient in VP-arm experienced >15 days interruption due to toxicity, and none in HFR-arm. In both arms, all patients received at least 60 Gy. In VP-arm, 8/26 patients had chemotherapy delay and/or dose reduction. In HFR-arm, 4/27 patients had <6 cycles cetuximab. There was no significant difference in overall survival (Median OS: 37.4 months vs 21.9 months, p = 0.12). Toxicities and DFS were not different between 2 arms.

Conclusions: Twice daily schedule of re-irradiation of 60 Gy/5 weeks with cetuximab was tolerable and no significant difference in treatment delays occurred between two arms.

Keywords: Cetuximab; Head and neck squamous cell carcinoma; Hyperfractionation; Re-irradiation; Recurrent or second primary.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy*
  • Cetuximab / administration & dosage
  • Chemoradiotherapy*
  • Female
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / therapy
  • Re-Irradiation / methods*
  • Salvage Therapy
  • Squamous Cell Carcinoma of Head and Neck


  • Cetuximab