Mature results of an individualized radiation dose prescription study based on normal tissue constraints in stages I to III non-small-cell lung cancer.
OBJECTIVE
We previously showed that individualized radiation dose escalation based on normal tissue constraints would allow safe administration of high radiation doses with low complication rate. Here, we report the mature results of a prospective, single-arm study that used this individualized tolerable dose approach.


METHODS
In total, 166 patients with stage III or medically inoperable stage I to II non-small-cell lung cancer, WHO performance status 0 to 2, a forced expiratory volume at 1 second and diffusing capacity of lungs for carbon monoxide >or= 30% were included. Patients were irradiated using an individualized prescribed total tumor dose (TTD) based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8 Gy fractions twice daily. Only sequential chemoradiation was administered. The primary end point was overall survival (OS), and the secondary end point was toxicity according to Common Terminology Criteria of Adverse Events (CTCAE) v3.0.


RESULTS
The median prescribed TTD was 64.8 Gy (standard deviation, +/- 11.4 Gy) delivered in 25 +/- 5.8 days. With a median follow-up of 31.6 months, the median OS was 21.0 months with a 1-year OS of 68.7% and a 2-year OS of 45.0%. Multivariable analysis showed that only a large gross tumor volume significantly decreased OS (P < .001). Both acute (grade 3, 21.1%; grade 4, 2.4%) and late toxicity (grade 3, 4.2%; grade 4, 1.8%) were acceptable.


CONCLUSIONS
Individualized prescribed radical radiotherapy based on normal tissue constraints with sequential chemoradiation shows survival rates that come close to results of concurrent chemoradiation schedules, with acceptable acute and late toxicity. A prospective randomized study is warranted to further investigate its efficacy.
van Baardwijk
Angela
A
Department of RadiationOncology (MAASTRO), GROWResearch Institute, Maastricht UniversityMedical Center, Maastricht. angela.vanbaardwijk@maastro.nl
Wanders
Stofferinus
S
Boersma
Liesbeth
L
Borger
Jacques
J
Ollers
Michel
M
Dingemans
Anne-Marie C
AM
Bootsma
Gerben
G
Geraedts
Wiel
W
Pitz
Cordula
C
Lunde
Ragnar
R
Lambin
Philippe
P
De Ruysscher
Dirk
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D011832:Radiation Injuries / Q000517:prevention & control; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D055752:Small Cell Lung Carcinoma / Q000473:pathology / Q000532:radiotherapy*; D016019:Survival Analysis