HI-CHART: a phase I/II study on the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer.
OBJECTIVE
To determine the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC).


METHODS
In a prospective, Phase I/II study, according to the risk for radiation pneumonitis, three risk groups were defined: V(20) <25%, V(20) 25-37%, and V(20) >37%. The dose was administered in three steps from 61.2 Gy/34 fractions/23 days to 64.8 Gy/36 fractions/24 days to 68.40 Gy/38 fractions/25 days (1.8 Gy b.i.d. with 8-h interval), using a three-dimensional conformal technique. Only the mediastinal lymph node areas that were positive on the pretreatment (18)F-deoxy-D-glucose positron emission tomography scan were included in the target volume. The primary endpoint was toxicity.


RESULTS
A total of 48 Stage I-IIIB patients were included. In all risk groups, 68.40 Gy/38 fractions/25 days could be administered. Maximal toxicity according to the risk groups was as follows: V(20) <25% (n = 35): 1 Grade 4 (G4) lung and 1 G3 reversible esophageal toxicity; V(20) 35-37% (n = 12): 1 G5 lung and 1 G3 reversible esophageal toxicity. For the whole group, local tumor recurrence occurred in 25% (95% confidence interval 14%-40%) of the patients, with 1 of 48 (2.1%; upper one-sided 95% confidence limit 9.5%) having an isolated nodal recurrence. The median actuarial overall survival was 20 months, with a 2-year survival rate of 36%.


CONCLUSIONS
High-dose continuous hyperfractionated accelerated radiotherapy up to a dose of 68.40 Gy/38 fractions/25 days (a biologic equivalent of approximately 80 Gy when delivered in conventional fractionation) in patients with inoperable NSCLC and a V(20) up to 37% is feasible.
De Ruysscher
Dirk
D
Department of Radiation Oncology, University Hospital Maastricht, GROW, Maastricht, The Netherlands. dirk.deruysscher@maastro.nl
Wanders
Rinus
R
van Haren
Erik
E
Hochstenbag
Monique
M
Geraedts
Wiel
W
Pitz
Cordula
C
Simons
Jean
J
Boersma
Liesbeth
L
Verschueren
Tom
T
Minken
Andre
A
Bentzen
Søren M
SM
Lambin
Philippe
P
D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary; D019583:Dose Fractionation, Radiation; D004947:Esophagus / Q000528:radiation effects; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy*; D008198:Lymph Nodes / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011446:Prospective Studies; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D020266:Radiotherapy, Conformal / Q000379:methods; D016019:Survival Analysis
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18