Maximum tolerated dose in a phase I trial on adaptive dose painting by numbers for head and neck cancer

Radiother Oncol. 2011 Dec;101(3):351-5. doi: 10.1016/j.radonc.2011.06.020.


Purpose: To determine the maximum tolerated dose (MTD) in a phase I trial on adaptive dose-painting-by-numbers (DPBN) for non-metastatic head and neck cancer.

Materials and methods: Adaptive intensity-modulated radiotherapy was based on voxel intensity of pre-treatment and per-treatment [(18)F]fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-FDG-PET) scans. Dose was escalated to a median total dose of 80.9 Gy in the high-dose clinical target volume (dose level I) and 85.9 Gy in the gross tumor volume (dose level II). The MTD would be reached, if ≥ 33% of patients developed any grade ≥ 4 toxicity (DLT) up to 3 months follow-up.

Results: Between February 2007 and August 2009, seven patients at dose level I and 14 at dose level II were treated. All patients completed treatment without interruption. At a median follow-up for surviving patients of 38 (dose level I) and 22 months (dose level II) there was no grade ≥ 4 toxicity during treatment and follow-up but six cases of mucosal ulcers at latency of 4-10 months, of which five (36%) were observed at dose level II. Mucosal ulcers healed spontaneously in four patients.

Conclusions: Considering late mucosal ulcers as DLT, the MTD of a median dose of 80.9 Gy has been reached in our trial.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Fluorodeoxyglucose F18*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Positron-Emission Tomography*
  • Radiotherapy Dosage
  • Radiotherapy, Image-Guided / methods*
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Radiotherapy, Intensity-Modulated / methods*


  • Fluorodeoxyglucose F18