Positron emission tomography-guided, focal-dose escalation using intensity-modulated radiotherapy for head and neck cancer.
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.
Madani
Indira
I
Department of Radiotherapy, Ghent University Hospital, Ghent, Belgium. indira@krtg1.ugent.be
Duthoy
Wim
W
Derie
Cristina
C
De Gersem
Werner
W
Boterberg
Tom
T
Saerens
Micky
M
Jacobs
Filip
F
Grégoire
Vincent
V
Lonneux
Max
M
Vakaet
Luc
L
Vanderstraeten
Barbara
B
Bauters
Wouter
W
Bonte
Katrien
K
Thierens
Hubert
H
De Neve
Wilfried
W
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
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18