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Impact of genetic variant of HIPK2 on the risk of severe radiation pneumonitis in lung cancer patients treated with radiation therapy.

ABSTRACT: BACKGROUND:Homeodomain-interacting protein kinase 2 (HIPK2) has increasingly drawn attention as recent researches demonstrated its unique role in the regulation of multiple fundamental processes such as apoptosis, proliferation and DNA damage repair. Most importantly, HIPK2 was shown to play regulatory role in inflammation and influence the phenotype and activity of fibroblasts. In this study, we aimed to evaluate the impact of HIPK2 gene variant on risk of radiation pneumonitis for patients with pulmonary malignancies. METHODS:169 lung cancer patients with radiotherapy were included in our prospective study and genotyped by Sanger Sequence method. Multivariable Cox hazard analysis and multiple testing were applied to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of all factors possibly related to the risk of radiation pneumonitis (RP). RESULTS:Patients with Mean Lung Dose (MLD)???15Gy, Lung V20???24% had higher risk of RP???grade 2 compared with those counterparts (HR?=?1.888, 95% CI: 1.186-3.004, P?=?0.007; HR?=?2.126, 95% CI: 1.338-3.378, P?=?0.001, respectively). Importantly, CC genotype of HIPK2: rs2030712 were strongly related to an increased occurrence of RP???grade 2 (HR?=?2.146, 95% CI: 1.215-3.791, P?=?0.009). CONCLUSION:HIPK2: rs2030712 was found to be significantly related to RP of grade???2 in our cohort, and may thus be one of the important predictors of severe RP before radiotherapy, if further validated in larger population. TRIAL REGISTRATION:Our study was prospective and observational. The research was registered in ClinicalTrials.gov database as NCT02490319.

SUBMITTER: Tang Y

PROVIDER: S-EPMC6950809 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Impact of genetic variant of HIPK2 on the risk of severe radiation pneumonitis in lung cancer patients treated with radiation therapy.

Tang Yang Y Yang Li L Qin Wan W Yi Min' Xiao MX Liu Bo B Yuan Xiang'Lin X

Radiation oncology (London, England) 20200108 1

<h4>Background</h4>Homeodomain-interacting protein kinase 2 (HIPK2) has increasingly drawn attention as recent researches demonstrated its unique role in the regulation of multiple fundamental processes such as apoptosis, proliferation and DNA damage repair. Most importantly, HIPK2 was shown to play regulatory role in inflammation and influence the phenotype and activity of fibroblasts. In this study, we aimed to evaluate the impact of HIPK2 gene variant on risk of radiation pneumonitis for pati ...[more]

PMID: 31915028

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Project description:Background:Radiation pneumonitis is a critical pulmonary toxicity after irradiation of the lung. Macrolides including clarithromycin (CAM) are antibiotics. They also have immunomodulatory properties and are used to treat respiratory inflammatory diseases. Radiation pneumonitis has similar pathology to them. Adverse reactions to macrolides are few and self-limited. We thus administered CAM to patients with high-risk factors for radiation pneumonitis, and retrospectively investigated whether CAM mitigated radiation pneumonitis following stereotactic body radiotherapy (SBRT). Methods:Among consecutive patients treated with SBRT, we retrospectively examined lung cancer patients treated with a total dose of 40-60 Gy in 5-10 fractions and followed ?6 months. Since January 2014, CAM has been administered in patients with pretreatment predictable radiation pneumonitis high-risk factors, including idiopathic interstitial pneumonias (IIPs), and elevated Krebs von den Lungen-6 (KL-6) and/or surfactant protein D (SP-D), and in patients developing early onset radiation pneumonitis. Results:Five hundred and eighty eligible patients were identified and divided into 445 patients during the non-CAM-administration era (non-CAM-era) (before December 2013) and 136 patients during the CAM-administration era (CAM-era) (after January 2014). Median follow-up durations were 38.0 and 13.9 months, respectively. The rates of radiation pneumonitis ? grade 2 and ? grade 3 were significantly lower in CAM-era (grade ?2, 16% vs. 9.6%, P=0.047; grade ?3, 3.8% vs. 0.73%, P=0.037). For patients with the pretreatment predictable high-risk factors, the rate of radiation pneumonitis ? grade 3 was significantly lower, and that of grade ?2 had a lower tendency (grade ?3, 7.2% vs. 0%, P=0.011; grade ?2, 21% vs. 9.6%, P=0.061). For patients developing early onset radiation pneumonitis, the rate of radiation pneumonitis ? grade 3 was also significantly lower (23% vs. 0%, P<0.05). Multivariate analysis revealed that dose-volumetric factor, the pretreatment predictable high-risk factors and non-CAM-administration era were significantly associated with or trended toward radiation pneumonitis ? grade 2 and ? grade 3. Conclusions:CAM mitigated radiation pneumonitis following SBRT. The efficacy of CAM should be con?rmed in prospective studies.

Dataset Information

Impact of genetic variant of HIPK2 on the risk of severe radiation pneumonitis in lung cancer patients treated with radiation therapy.

Publications

Impact of genetic variant of HIPK2 on the risk of severe radiation pneumonitis in lung cancer patients treated with radiation therapy.

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