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Clinical significance of BIM deletion polymorphism on chemoradiotherapy in patients with non-small cell lung cancer.

若林 優 広島大学

2021.03.23

概要

The standard treatment for locally advanced non-small cell lung cancer (NSCLC)
is chemoradiotherapy (CRT) followed by anti-programmed cell death-ligand 1 (antiPD-L1) treatment. BIM deletion polymorphism induces the suppression of apoptosis
resulting from epidermal growth factor (EGFR)-tyrosine kinase inhibitors in EGFRmutated NSCLC patients. We aimed to examine the effects of BIM polymorphism on
CRT and anti-PD-L1/PD-1 treatment in NSCLC patients. In this retrospective study of
1312 patients with unresectable NSCLC treated at Higashi-Hiroshima Medical Center
and Hiroshima University Hospital between April 1994 and October 2019, we enrolled
those who underwent CRT or chemotherapy using carboplatin + paclitaxel or cisplatin + vinorelbine, or anti-PD-L1/PD-1 treatment. Of 1312 patients, 88, 80, and 74
underwent CRT, chemotherapy, and anti-PD-L1/PD-1 treatment, respectively, and
17.0%, 15.2% and 17.6% of these patients showed BIM polymorphism. Among patients
receiving CRT, the progression-free survival was significantly shorter in those with BIM
deletion than in those without. In the multivariate analyses, BIM polymorphism was
an independent factor of poor anti-tumor effects. These results were not observed
in the chemotherapy and anti-PD-L1/PD-1 treatment groups. In in vitro experiments,
BIM expression suppression using small interfering RNA in NSCLC cell lines showed
a significantly suppressed anti-tumor effect and apoptosis after irradiation but not
chemotherapy. In conclusion, we showed that BIM polymorphism was a poor-predictive factor for anti-tumor effects in NSCLC patients who underwent CRT, specifically
radiotherapy. In the implementation of CRT in patients with BIM polymorphism, we
should consider subsequent treatment, keeping in mind that CRT may be insufficient. ...

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参考文献

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S U P P O R T I N G I N FO R M AT I O N

Additional supporting information may be found online in the

Supporting Information section.

How to cite this article: Wakabayashi Y, Masuda T, Fujitaka

K, et al. Clinical significance of BIM deletion polymorphism in

chemoradiotherapy for non-small cell lung cancer. Cancer Sci.

2020;00:1–11. https://doi.org/10.1111/cas.14711

...

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