title: Positron emission tomography-guided, focal-dose escalation using intensity-modulated radiotherapy for head and neck cancer.
abstract: OBJECTIVE
  To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer.
  
  
  METHODS
  A Phase I clinical trial was designed to escalate the dose limited to the [(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy.
  
  
  RESULTS
  Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p = n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted (18)F-FDG-PET-delineated region.
  
  
  CONCLUSIONS
  For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.
authors: Department of Radiotherapy, Ghent University Hospital, Ghent, Belgium. indira@krtg1.ugent.be
authors: Indira
authors: I
authors: Madani
authors: Wim
authors: W
authors: Duthoy
authors: Cristina
authors: C
authors: Derie
authors: Werner
authors: W
authors: De Gersem
authors: Tom
authors: T
authors: Boterberg
authors: Micky
authors: M
authors: Saerens
authors: Filip
authors: F
authors: Jacobs
authors: Vincent
authors: V
authors: Grégoire
authors: Max
authors: M
authors: Lonneux
authors: Luc
authors: L
authors: Vakaet
authors: Barbara
authors: B
authors: Vanderstraeten
authors: Wouter
authors: W
authors: Bauters
authors: Katrien
authors: K
authors: Bonte
authors: Hubert
authors: H
authors: Thierens
authors: Wilfried
authors: W
authors: De Neve
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D017211:Treatment Failure
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18