Low-Cost Genetic and Clinical Predictors of Response and Toxicity of Platinum-Based Chemotherapy in Advanced Non-Small Cell Lung Cancer

晚期非小细胞肺癌铂类化疗疗效和毒性的低成本遗传和临床预测因素

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作者:Jelena Spasic, Milena Cavic, Nemanja Stanic, Bojan Zaric, Tomi Kovacevic, Davorin Radosavljevic, Ljudmila Nagorni-Obradovic

Background

This study aimed to evaluate for the first time whether certain genetic and clinical factors could serve as minimally invasive predictors of survival and toxicity to platinum-based chemotherapy in advanced lung adenocarcinoma.

Conclusions

A set of easily determined genetic and clinical predictors of survival and specific toxicity profiles of platinum-based chemotherapy in advanced lung adenocarcinoma were determined in this study, which might be useful for the construction of population-specific, time- and cost-efficient prognostic and predictive algorithms.

Methods

The study included 121 advanced lung adenocarcinoma patients treated with platinum-based dublets until progression or unacceptable toxicity. Response was evaluated using standard radiological methods and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Genotyping was performed using PCR-RFLP. Statistical significance was set at P < .05.

Results

No significant influence of the examined polymorphisms on the occurrence of high-grade toxicity was detected. However, TP53 72Pro allele carriers were more prone to nausea (P = .037) and thrombocytopenia (P = .051). Anemia and neuropathy occurred more frequently in XRCC1 399Arg allele carriers (Pearson χ2 test, P = .025 and P = .004 respectively). RAD51 135CC carriers were significantly more prone to neutropenia (P = .027). Conclusions: A set of easily determined genetic and clinical predictors of survival and specific toxicity profiles of platinum-based chemotherapy in advanced lung adenocarcinoma were determined in this study, which might be useful for the construction of population-specific, time- and cost-efficient prognostic and predictive algorithms.

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