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A sequence polymorphism on 8q24 is associated with survival in hepatocellular carcinoma patients who received radiation therapy.

ABSTRACT: There is a growing consensus that genetic variation in candidate genes can influence cancer progression and treatment effects. In this study, we genotyped the rs9642880 G?>?T polymorphism using DNA isolated from blood samples of 271 hepatocellular carcinoma (HCC) patients who received radiotherapy treatment. We found that patients who carried the GT or TT genotypes had significantly shorter median survival times (MSTs) compared to patients with the GG genotype (14.6 vs.21.4 months). The multivariate P value was 0.027, the hazard ratio (HR) was 1.38, and the 95% confidence interval was 1.04-1.84. Further analysis revealed that patients with the variant genotypes had an increased risk of poor tumour response to radiotherapy (P?=?0.036 and 0.002 for stable disease and progressive disease, respectively) and higher incidence of multiple intrahepatic lesions (P?=?0.026) and BCLC C stage (P?=?0.027). Moreover, further stratified survival analyses revealed that at least radioresponse and BCLC stage contributed to the association between the rs9642880 G?>?T polymorphism and survival of HCC patients in this study (P value, 0.017 vs 0.053 for BCLC C stage vs B stage; 0.011 vs 0.531 for radioresponse SD?+?PD vs CR?+?PR). These results illustrate the potential association between rs9642880 G?>?T and survival in HCC patients who received radiotherapy treatment.

SUBMITTER: Zhao XM

PROVIDER: S-EPMC5797243 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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A sequence polymorphism on 8q24 is associated with survival in hepatocellular carcinoma patients who received radiation therapy.

Zhao Xiao-Mei XM Xiang Zuo-Lin ZL Chen Yi-Xing YX Yang Ping P Hu Yong Y Zeng Zhao-Chong ZC

Scientific reports 20180202 1

There is a growing consensus that genetic variation in candidate genes can influence cancer progression and treatment effects. In this study, we genotyped the rs9642880 G > T polymorphism using DNA isolated from blood samples of 271 hepatocellular carcinoma (HCC) patients who received radiotherapy treatment. We found that patients who carried the GT or TT genotypes had significantly shorter median survival times (MSTs) compared to patients with the GG genotype (14.6 vs.21.4 months). The multivar ...[more]

PMID: 29396413

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Project description:BackgroundMore than 70% of patients with hepatocellular carcinoma (HCC) are not candidates for curative therapy or recur after curative-intent therapy. There is growing evidence on the use of ablative radiation therapy (RT) for liver tumors. We aimed to analyze outcomes of HCC patients treated with conventional versus ablative RT.MethodsWe retrospectively analyzed medical records of HCC patients treated with liver RT from 2001 to 2019. We defined ablative RT as biologically effective dose (BED) ≥80 Gy. RECIST 1.1 was used to define early responses at 3-6 months after RT, and local control (LC) at last follow-up (FU). Data was analyzed using Fisher exact test, Kaplan-Meier, cumulative incidence rates, Cox proportional hazards model and Fine-Gray competing risks.ResultsForty-five patients were identified, of whom 14 (31.1%) received ablative RT using a stereotactic technique. With median FU of survivors of 10.1 months, 1-year cumulative incidence of LC was 91.7% for ablative and 75.2% for BED <80 Gy. At early FU, patients treated with ablative RT had better responses compared to BED <80 Gy, with 7% progressing versus 19%, and 21.4% with complete response versus none (P=0.038). On univariate analysis (UVA), Child-Pugh (CP) score [hazard ratio (HR): 3 for CP-B, HR: 16 for CP-C] and BED (HR: 7.69 for BED <80 Gy) correlated with deterioration of liver function, leading to liver failure. Most liver failure cases were due to disease progression. No RT-related liver failure occurred in the ablative RT group. On UVA, only BED ≥80 Gy was associated with improved overall survival (OS) (HR: 0.4; P=0.044). Median OS (mOS) and 1-year OS were 7 months and 35% respectively for BED <80 Gy compared to 28 months and 66% for BED ≥80 Gy. No grade 3+ bowel toxicity was reported in either group.ConclusionsGreater than 90% LC was achieved after stereotactic ablative RT, which was associated with minimized tumor- and treatment-related liver failure and improved survival for highly selected inoperable HCC patients.

Project description:IntroductionFirst-line systemic therapy (ST) options for advanced hepatocellular carcinoma (HCC) include tyrosine kinase inhibitors and immunotherapy (IO). Evolving data suggest prolonged overall survival (OS) when ST is combined with stereotactic body radiation therapy (SBRT), although evidence is significantly limited in HCC populations. We hypothesized that advanced HCC patients in the National Cancer Database (NCDB) would have improved OS when receiving ST+SBRT vs ST alone.MethodsStage III/IV HCC patients diagnosed from 2010-2020 and treated with first-line ST±SBRT were identified from the NCDB. The primary endpoint was OS from date of diagnosis stratified by the receipt of SBRT (ST+SBRT vs ST alone). Survival was estimated using Kaplan-Meier methodology and compared via log-rank. Multivariate analysis (MVA) was performed by Cox regression.ResultsOf 10,505 eligible patients with stage III disease, 115 (1.1%) received ST+SBRT and 10,390 (98.9%) received ST alone. Of 9,617 eligible patients with stage IV disease, 127 (1.3%) received ST+SBRT and 9,490 (98.7%) received ST alone. Median follow-up time was 6.8 months. Baseline characteristics were similar between cohorts. Patients with stage III disease receiving ST+SBRT had improved median OS (12.62 months vs 8.38 months) and higher rates of survival at 1-year (53.0% vs 38.7%) and 2-years (27.0% vs 20.7%) compared to those receiving ST alone (log-rank P=0.0054). Similarly, patients with stage IV disease receiving ST+SBRT had improved median OS (11.79 months vs 5.72 months) and higher rates of survival at 1-year (49.6% vs 26.2%) and 2-years (23.6% vs 12.0%) (log-rank P<0.0001). On MVA, receipt of SBRT predicted improved OS (HR=0.748, 95%CI 0.588-0.951; P=0.0178) and receipt of IO trended towards improved OS (HR=0.859, 95%CI 0.735-1.003; P=0.0538).ConclusionIn advanced HCC, patients receiving ST+SBRT had improved OS compared to those receiving ST alone. Prospective clinical trials are warranted to better identify HCC populations which may benefit from combined modality therapy.

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A sequence polymorphism on 8q24 is associated with survival in hepatocellular carcinoma patients who received radiation therapy.

Publications

A sequence polymorphism on 8q24 is associated with survival in hepatocellular carcinoma patients who received radiation therapy.

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