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THRB genetic polymorphisms can predict severe myelotoxicity after definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma.

ABSTRACT: OBJECTIVE:Chemotherapy-related toxicities are difficult to predict before treatment. In this study, we investigated whether thyroid hormone receptor beta (THRB) genetic polymorphisms can serve as a potential biomarker in patients with esophageal squamous cell carcinoma (ESCC). METHODS:Forty-nine Japanese patients with ESCC who received a definitive chemoradiotherapy (CRT) with 5-fluorouracil and cisplatin in conjunction with concurrent irradiation were retrospectively analyzed. Severe acute toxicities, including leukopenia, stomatitis, and cheilitis, were evaluated according to 6 single nucleotide polymorphisms (SNPs) in the gene; the intronic SNPs of rs7635707 G/T, rs6787255 A/C, rs9812034 G/T, and rs9310738 C/T and the SNPs in the 3'-untranslated region (3'-UTR) of rs844107 C/T and rs1349265 G/A. RESULTS:Distribution of the 4 intronic SNPs, but not the 2 SNPs in the 3'-UTR, showed a significant difference between patients with and without severe acute leukopenia. Stomatitis and cheilitis were not associated with any of the 6 analyzed SNPs. Frequency of haplotype of the 4 intronic SNPs reached approximately 97% with the 2 major haplotypes G-A-G-C (73.4%) and T-C-T-T (23.5%). CONCLUSIONS:THRB intronic SNPs can provide useful information on CRT-related severe myelotoxicity in patients with ESCC. Future studies will be needed to confirm these findings.

SUBMITTER: Miki I

PROVIDER: S-EPMC3491433 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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THRB genetic polymorphisms can predict severe myelotoxicity after definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma.

Miki Ikuya I Nakamura Tsutomu T Kuwahara Akiko A Yamamori Motohiro M Nishiguchi Kohshi K Tamura Takao T Okuno Tatsuya T Omatsu Hideaki H Mizuno Shigeto S Hirai Midori M Azuma Takeshi T Sakaeda Toshiyuki T

International journal of medical sciences 20121023 9

<h4>Objective</h4>Chemotherapy-related toxicities are difficult to predict before treatment. In this study, we investigated whether thyroid hormone receptor beta (THRB) genetic polymorphisms can serve as a potential biomarker in patients with esophageal squamous cell carcinoma (ESCC).<h4>Methods</h4>Forty-nine Japanese patients with ESCC who received a definitive chemoradiotherapy (CRT) with 5-fluorouracil and cisplatin in conjunction with concurrent irradiation were retrospectively analyzed. Se ...[more]

PMID: 23136537

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Project description:BackgroundThe objective of this study was to investigate the relationship between clinical characteristics, as well as dosimetric parameters, and the risk of treatment-related lymphopenia in esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT).Materials and methodsClinical characteristics and dosimetric parameters were collected from 436 patients with ESCC who received definitive CRT from 2010 through 2017. Absolute lymphocyte counts (ALCs) were obtained before, during, and 1 month after CRT. Grade 4 (G4) lymphopenia was defined as ALC <0.2 × 109 /L during CRT. Logistic regression analysis was used to evaluate the effect of each factor on predicting G4 lymphopenia. The relationship between lymphopenia and overall survival (OS) was examined, and a nomogram was developed to predict OS.ResultsG4 lymphopenia was observed in 103 patients (23.6%) during CRT. Multivariate analysis indicated that planning target volume (PTV), lung V10 , heart V10 , performance status, and pretreatment lymphopenia were significant risk factors for G4 lymphopenia. Patients with G4 lymphopenia had significantly worse survival than those without. Based on multivariate analysis, clinical TNM stage, radiotherapy modality, pretreatment ALC, and G4 lymphopenia were predictive of OS and were incorporated into the nomogram, yielding a concordance index of 0.71.ConclusionsG4 lymphopenia during definitive CRT was associated with larger PTVs, higher lung V10 and heart V10 , and worse survival.Implications for practiceThe purpose of this study was to investigate the relationship between clinical characteristics, as well as dosimetric parameters, and the risk of treatment-related lymphopenia in 436 patients with esophageal squamous cell carcinoma who received definitive chemoradiotherapy. Grade 4 (G4) lymphopenia was observed in 23.6% of patients during radiotherapy. G4 lymphopenia was associated with larger planning target volumes, higher lung V10 and heart V10 , and worse survival. Then, a nomogram was built based on multivariate analysis, yielding excellent performance to predict overall survival. Prospective studies are needed to investigate potential approaches for mitigating severe lymphopenia, which may ultimately convert into survival benefits.

Dataset Information

THRB genetic polymorphisms can predict severe myelotoxicity after definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma.

Publications

THRB genetic polymorphisms can predict severe myelotoxicity after definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma.

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