Precision Hypofractionated Radiation Therapy in Poor Performing Patients with Non-Small Cell Lung Cancer: Phase I Dose Escalation Trial
Mené sur 55 patients atteints d'un cancer du poumon non à petites cellules de stade II-IV ou récidivant et dont le niveau de performance physique selon l'échelle du système ECOG est supérieur ou égal à 2 (durée médiane de suivi : 12,5 mois), cet essai de phase I évalue la tolérabilité de différentes doses de radiothérapie hypofractionnée
Purpose : Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. Objective : To escalate radiotherapy to a tumorcidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials : Patients with stage II-IV, or recurrent NSCLC with ECOG performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to intrathoracic disease in 15 fractions to a total of 50, 55 or 60 Gy. Results : 55 patients were enrolled: 15 at the 50 Gy, 21 at the 55 Gy, and 19 at the 60 Gy dose levels. 90-day follow-up was completed in each group without exceeding the MTD. With a median follow up of 12.5 months there were 93 total grade ≥3 AE's including 39 deaths, although most AE's were considered related to factors other than radiation therapy. One patient from the 55 and 60 Gy dose groups developed grade ≥3 esophagitis and 5, 4 and 4 patients in the respective dose groups experienced grade ≥3 dyspnea but only 2 of these were considered likely related to therapy. There was no association between fraction size and toxicity (p=0.24). The median overall survival was 6 months with no significant differences between dose levels (p=0.59). Conclusions : Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost-effectiveness of lung cancer therapy. Additional studies of the long term safety and efficacy of this therapy are warranted.