Preliminary Study of Clinical Role of Circulating Tumor Cells in Patients with Small-Cell Lung Cancer Treated By Prophylactic Cranial Irradiation

Abstract

Prophylactic cranial irradiation (PCI) decreases the rate of brain metastases, and improves the overall survival (OS) of small-cell lung cancer (SCLC). However, the improvement of OS is uncertain under the era of MRI. The circulating tumor cells (CTCs) play a vital role in recurrence, prognosis, efficacy evaluation, and individualized therapy of cancer patients. Our aims to investigate the preliminary clinical value of CTCs in SCLC patients treated by PCI. In this prospective study comparing two different thoracic radiotherapy regimens, SCLC patients received chemo-radiotherapy and subsequent PCI after brain metastases were excluded by MRI screening. The blood samples for CTCs analysis were obtained from 20 SCLC patients before and after PCI. Instead of the CellSearch system, CTCs were assessed with a new detection method based on telomerase-specific, replication-selective oncolytic herpes simplex virus-1 that targets telomerase reverse transcriptase-positive cancer cells and expresses a green fluorescent protein that identifies CTCs (oHSV1-hTERT-GFP), with high sensitivity and specificity in lung cancer patients. The endpoints were progression-free survival (PFS) and OS. Eleven patients were limited-stage SCLC, and 9 were extensive-stage SCLC. The CTCs detection rate was 100%. The follow-up time was 39.2 months for the whole group. Seven patients failed with distant metastases. The median CTCs count were 12 (range, 1-43) before PCI, and 4 (range, 0-34) after PCI. Logistic regression showed the CTCs count was not associated with the clinical parameters. Patients with ≥12 CTCs before PCI tended to show worse PFS and OS than those with <12 CTCs (31.8 months vs not reached, p = 0.084; not reached vs not reached, p = 0.457). Six in 12 patients with ≥12 CTCs failed, but only 1 relapsed in 8 patients with <12 CTCs before PCI. PFS and OS were significantly different in patients with ≥4 CTCs after PCI and those with <4 CTCs (28.1 months vs not reached, p = 0.001; not reached vs not reached, p = 0.029). All 10 patients were alive without disease in the group with <4 CTCs, however, 7 relapsed in 10 patients with ≥4 CTCs after PCI. Significantly better PFS and OS were found in 10 patients with the reduction rate of more than 58% than other 10 patients with less than 58% (not reached vs 26.4 months, p = 0.006; not reached vs not reached, p = 0.029). CTCs counts after PCI and CTCs reduction rate are valuable prognostic markers of better survival of SCLC patients. Patients with the high CTCs reduction rate could benefit from PCI. However, the prognostic significance of CTCs needs to be evaluated in large-scale clinical trials.