A Pilot Study of FDG PET Lung Uptake After Thoracic Radiation Therapy and New Pulmonary Symptoms

Abstract

It has been recently reported that a single nucleotide polymorphism (SNP) signature composed of ERCC1/2 genes (ERCC1:rs11615 and ERCC2:rs238406) was predictive of radiosensitivity in stage-III non-small cell lung cancer (NSCLC). That is, at relatively low radiation doses (<70 Gy), patients with a radiosensitive genotype would have better treatment outcome than those with a radioresistant genotype. On the other hand, at relatively high doses (>80 Gy), these radiosensitive patients would have worse treatment outcome due to overdose-related adverse effects. Patients with stereotactic body radiation therapy (SBRT) usually receive very high dose (>80 Gy equivalently). This study aimed to test if the radiosensitive patients predicted by the SNP signature would indeed have a poorer overall survival after SBRT. Materials/Methods: A total of 26 stage I-II NSCLC patients who enrolled in an IRB proved biomarker protocol and underwent SBRT treatment were included in this study. Four different dose regimens, with the minimum equivalent biological dose at 2 Gy/fraction being 83 Gy, were used. The SNPs of ERCC1: rs11615 and ERCC2:rs238406 were genotyped for each patient. Minimum follow-up time was 22 months. Results: The ERCC2 SNP had a <70% call rate for these patients so that it was excluded for the analysis. The ERCC1 SNP had a 100% call rate. Seven patients had the radio-resistant genotype, and 19 had the radiosensitive genotype. The patients with the radio-resistant genotype showed statistically significant better overall survival than the patients with radiosensitive genotype (P < 0.05). Only 1 radio-resistant patient died after 28 months from a surgical procedure to remove a new colon cancer, and all others were alive at the last follow-up date, with minimum follow-up of 27 months. On the other hand, the radiosensitive patients had a medium survival of 23 months, with a 10/19 death rate. The causes of death were distance metastasis (2), cardiac events (2) and unknown (6). For the 6 patients died with unknown cause, one had grade 3 acute lung toxicity, three had grade 2-3 late lung toxicity. There was no significant difference of gender, age, stage, and radiation regimens between the 2 genotype groups. However, there were 3 out of 7 African-Americans in the radio-resistant group, but only 1 out of 19 in the radiosensitive group, consistent with the reports that the African-Americans have much higher frequency in the genotype corresponding to radio-resistant for this SNP. Conclusion: Although limited number of patients, this study supported the previous finding that the SNP ERCC1:rs11615 can serve as a radiosensitivity marker. The radiosensitive patients showed poorer overall survival than the radio-resistant patients after high dose SBRT treatment, possibly due to too-high radiation dose to the normal tissue, suggesting that dose de-escalation may improve survival for the radiosensitive patients in SBRT.