Pulmonary artery invasion, high-dose radiation, and overall survival in patients with non-small cell lung cancer

Abstract

Purpose: To investigate whether high-dose radiation to the pulmonary artery (PA) affects overall survival (OS) in patients with non-small cell lung cancer (NSCLC).

Methods and materials: Patients with medically inoperable/unresectable NSCLC treated with definitive radiation therapy in prospective studies were eligible for this study. Pulmonary artery involvement was defined on the basis of pretreatment chest CT and positron emission tomography/CT fusion. Pulmonary artery was contoured according to the Radiation Therapy Oncology Group protocol 1106 atlas, and dose-volume histograms were generated.

Results: A total of 100 patients with a minimum follow-up of 1 year for surviving patients were enrolled: 82.0% underwent concurrent chemoradiation therapy. Radiation dose ranged from 60 to 85.5 Gy in 30-37 fractions. Patients with PA invasion of grade ≤2, 3, 4, and 5 had 1-year OS and median survival of 67% and 25.4 months (95% confidence interval [CI] 15.7-35.1), 62% and 22.2 months (95% CI 5.8-38.6), 90% and 35.8 months (95% CI 28.4-43.2), and 50% and 7.0 months, respectively (P=.601). Two of the 4 patients with grade 5 PA invasion died suddenly from massive hemorrhage at 3 and 4.5 months after completion of radiation therapy. Maximum and mean doses to PA were not significantly associated with OS. The V45, V50, V55, and V60 of PA were correlated significantly with a worse OS (P<.05). Patients with V45 >70% or V60 >37% had significantly worse OS (13.3 vs 37.9 months, P<.001, and 13.8 vs 37.9 months, P=.04, respectively).

Conclusions: Grade 5 PA invasion and PA volume receiving more than 45-60 Gy may be associated with inferior OS in patients with advanced NSCLC treated with concurrent chemoradiation.

Figure 1

Pulmonary artery (PA) contouring according to RTOG 1106 atlas A: PA contour starts at this level, B: Left PA trunk, C: Right PA trunk, D: Left PA ends at this level, E: PA trunk and right PA, F: Right PA ends at this level.

Figure 2

CT Grading system of PA invasion. A, B, C, D, E, F, G and H are grade −2, −1, 0, 1, 2, 3, 4 and 5 respectively. White arrow indicates PA invasion. A: Grade −2, >20mm from the closest vessel wall; B: Grade −1, 5-20mm from the closest vessel wall; C: Grade 0, no evidence of vessel invasion, 1-5mm from the closest vessel wall; D: Grade 1, <50% circumferential involvement without presence of narrowing or truncation of vessels; E: Grade 2, >50% circumferential involvement without presence of narrowing or truncation of vessels; F: Grade 3, smooth narrowing without truncation; G: Grade 4, presence of truncation of left PA; H: Grade 5, tumor encasing, narrowing, and invading left PA extensively, with presence of irregularity, and invading 2 great vessels (left PA and descending aorta) I,J: Example CT scans of two patients with grade 5 PA invasion died from massive hemorrhage at 3 and 4.5 months respectively after radiotherapy.

Figure 3

Pulmonary Artery (PA) invasion, radiation dose, dose volume of PA and overall survival. A: PA invasion and overall survival. MS= median survival B: Radiation dose and overall survival. C: Dose volume of PA and overall survival. D: RT dose and PA V45 (70%). There was no linear correlation between RT dose and PA V45. However, overall survivals were significantly different between PA V45 ≤70% vs. PA V45 > 70%, MS 23.0 (95% CI 2.0-44.1) months vs. 13.3 (95% CI 11.4-15.2) months (P=0.016) in patients received RT ≤70 Gy. In patients with PA 45 ≤70%, patients received RT >70 Gy survived significant better, with MS of 42.6 (95% CI 35.9-49.3) months in RT >70 Gy vs 23.0 (95% CI 2.0-44.1) months of RT ≤70 Gy (P=0.015).