Preoperative carbon ion radiotherapy for non-small cell lung cancer with chest wall invasion—pathological findings concerning tumor response and radiation induced lung injury in the resected organs

Abstract

The purpose of this study was to make a pathological evaluation of the tumor response and the lung injury of non-small cell lung cancer (NSCLC) patients after carbon ion therapy. We enrolled four NSCLC patients with chest wall invasion but without nodal and distant metastasis (T3N0M0). Only primary lesions were irradiated with carbon ions, followed by surgical resection. The patients consisted of three males and one female varying by age from 54 to 73 (average 66.3). Total treatment dose was 59.4 and 64.8 GyE, respectively, administered in 18 fractions over 6 weeks, or 72.0 GyE in 16 fractions over 4 weeks. Resection after radiation therapy was performed as a combination of lobectomy, lymph node dissection and chest wall surgery. After fixation, the lung was sliced into thin sections to match the CT image. Each slice was anatomically identified and the slices were compared with each other subjected to pathological analysis. No tumor cells were observed in two cases. The other two cases exhibited only a few tumor cells sparsely distributed in the lung tissue. There was evidence of dense pulmonary fibrosis in the limited space surrounding primary tumors, but its density was found to rapidly decrease in the narrow area toward the outside. The rate at which its density subsided mirrored the rapid decrease in the planning CT dose distribution. Microscopy showed no evidence of fibrosis in any of the fields irradiated with less than 15 GyE. Microscopy confirmed an outstanding tumor response with limited pulmonary fibrosis. This substantiates the superior dose localization and strong biological effect of carbon ion beams with a Bragg peak in the lung. The pathological findings have thus provided evidence of the safety and effectiveness of carbon beam therapy in the treatment of NSCLC.