Intensity-modulated radiotherapy for locally advanced non-small-cell lung cancer: a dose-escalation planning study.
OBJECTIVE
To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC).


METHODS
For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity).


RESULTS
IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p ≤.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD.


CONCLUSIONS
In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.
Lievens
Yolande
Y
Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium. yolande.lievens@uzleuven.be
Nulens
An
A
Gaber
Mousa Amr
MA
Defraene
Gilles
G
De Wever
Walter
W
Stroobants
Sigrid
S
Van den Heuvel
Frank
F
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D018287:Carcinoma, Large Cell / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D004947:Esophagus / Q000528:radiation effects; D005260:Female; D006321:Heart / Q000528:radiation effects; D006801:Humans; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects; D011336:Probability; D011832:Radiation Injuries / Q000517:prevention & control; D011877:Radionuclide Imaging; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D020266:Radiotherapy, Conformal / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D013116:Spinal Cord / Q000528:radiation effects