Dataset Information

Genetic variants of SP-D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy.

ABSTRACT:

Background

Surfactant protein D (SP-D) is an innate immunity molecule in the alveoli. However, the associations between genetic variants of SP-D and radiation pneumonitis (RP) have never been investigated.

Methods

The Linkage disequilibrium of SP-D and tagSNPs were analyzed by using Haploview 4.1. Eight tagSNPs were genotyped among 396 lung cancer patients who received thoracic radiation therapy with follow-up time (median [P25, P75]: 11[6, 18]) using improved multiplex ligation detection reaction (iMLDR). The associations between clinical characteristics, tagSNP alleles, genotypes, haplotypes and onset time of grade ≥2 or ≥3 RP were evaluated by using univariate and multivariate Cox proportional hazard regression model.

Results

Three tagSNPs of SP-D (rs1998374, rs911887 and rs2255326) were significantly associated with grade ≥2 RP in multivariate analysis with multiple testing (Q test). The rs199874 had a protective effect for grade ≥2 RP in the dominant model (Hazard ratio (HR), 0.575; 95% confidence interval (CI), 0.378-0.875). The homozygous mutant genotype for rs911887 had risk effect for grade ≥2 RP (HR, 2.209; 95% CI, 1.251-3.902). The A mutant allele of rs2255326 also showed an elevated risk for grade ≥2 RP (HR, 1.777; 95% CI, 1.283-2.461) and this risk effect was still significant in the recessive genetic model (HR, 3.320; 95% CI, 1.659-6.644) and dominant genetic model (HR, 1.773; 95% CI, 1.166-2.696). Compared to the lung cancer patients bearing the most common haplotype C-G-T, the patients bearing the haplotype T-A-C (rs1998374-rs2255326-rs911887) showed a significant risk of both grade ≥2 RP (HR, 1.885; 95% CI, 1.284-2.765) and grade ≥3 RP (HR, 2.256; 95% CI, 1.248-4.080).

Conclusions

Genetic variants of SP-D were associated with risk of RP development in lung cancer patients receiving thoracic radiotherapy.

SUBMITTER: Xu L

PROVIDER: S-EPMC6536953 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Genetic variants of SP-D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy.

Xu Li L Jiang Junhong J Li Yunming Y Zhang Ling L Li Zhihui Z Xian Jing J Jiang Chaoyang C Diao Yong Y Su Xiaomei X Xu Hongyu H Zhang Yue Y Zhang Tao T Yang Zhenzhou Z Tan Bangxian B Li Hua H

Cancer medicine 20190321 5

<h4>Background</h4>Surfactant protein D (SP-D) is an innate immunity molecule in the alveoli. However, the associations between genetic variants of SP-D and radiation pneumonitis (RP) have never been investigated.<h4>Methods</h4>The Linkage disequilibrium of SP-D and tagSNPs were analyzed by using Haploview 4.1. Eight tagSNPs were genotyped among 396 lung cancer patients who received thoracic radiation therapy with follow-up time (median [P25, P75]: 11[6, 18]) using improved multiplex ligation d ...[more]

PMID: 30897289

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Project description:PurposeWhilst survival benefits of thoracic radiotherapy (TRT) followed by immune checkpoint inhibitor (ICI) have been reported in patients with lung cancer, the potential high risk of treatment-related pneumonitis remains a concern. Asians may be more sensitive to lung toxicity than other races. This retrospective study intended to provide a comprehensive pneumonitis profile of TRT followed by ICI and investigate the risk factors from a Chinese cohort of lung cancer.Methods and materialsFrom January 2016 to July 2021, 196 patients with lung cancer who received TRT prior to ICI were retrospectively analyzed. Treatment-related pneumonitis, including checkpoint inhibitor pneumonitis (CIP), radiation pneumonitis (RP), and radiation recall pneumonitis (RRP), were recorded and graded through medical records and chest computed tomography. Characteristics predictive of pneumonitis were assessed using logistic regression models, and the receiver operating characteristic analyses were performed to identify optimal cut points for quantitative variables.ResultsWith a median follow-up of 18 months, a total of 108 patients (55.1%) developed treatment-related pneumonitis during ICI therapy, with an incidence of 25.5% for grade 2 or higher (G2+) and 4.1% for G3+. The overall rates of CIP, RP and RRP were 8.2% (n=16), 46.9% (n=92) and 7.1% (n=14), respectively. With a total mortality rate of 1.5%, vast majority of the patients recovered from pneumonitis or remained stable. No patients died of RRP. Half of the patients with G2+ RP who withheld ICI therapy restarted ICI safely after resolution of RP. The history of chronic pulmonary diseases (P=0.05), mean lung dose (MLD, P=0.038), percent volume of lung receiving ≥5 Gy (V5, P=0.012) and percent volume of lung receiving ≥20 Gy (V20, P=0.030) predicted the occurrence of RRP in univariate analyses. Interval between TRT and ICI less than 3 months was an independent predictor for G2+ treatment-related pneumonitis in a multivariate model (Odds ratio OR=2.787, P=0.004).ConclusionsTreatment-related pneumonitis, especially RRP, is acceptable and manageable in the setting of TRT followed by ICI in this Asian population. Dosimetric parameters MLD, V5 and V20 may improve the predictions of RRP in clinical practice.

Project description:PurposeRadiation pneumonitis (RP) is a common and potentially life-threatening toxicity from lung cancer radiation therapy. Data sets reporting RP rates after postoperative radiation therapy (PORT) have historically been small and with predominantly outdated field designs and radiation techniques. We examined a large cohort of patients in this context to assess the incidence and causes of RP in the modern era.Methods and materialsWe reviewed 285 patients with non-small cell lung cancer treated with PORT at our institution from May 2004 to January 2017. Complete dosimetric data and clinical records were reviewed and analyzed with grade 2 or higher RP as the endpoint (RP2+) (Common Terminology Criteria for Adverse Events v4.0). Patients were a median of 67 years old (range, 28-87), and most had pathologic stage III non-small cell lung cancer (91%) and received trimodality therapy (90%). Systematic dosimetric analyses using Dx increments of 5% and Vx increments of 2 Gy were performed to robustly evaluate dosimetric variables. Lung V5 was also evaluated.ResultsThe incidence of RP2+ after PORT was 12.6%. Dosimetric factors most associated with RP2+ were total lungV4 (hazard ratio [HR] 1.04, P < .001) and heart V16 (HR 1.03, P = .001). On univariate analysis, the clinical factors of age (HR 1.05, P = .006) and carboplatin chemotherapy (HR 2.32, P = .012) were correlated with RP2+. On step-up multivariate analysis, only bivariate models remained significant, including lungV5 (HR 1.037, P < .001) and age (HR 1.052, P = .011).ConclusionsThe incidence of RP after PORT is consistent with the literature. Factors correlated with RP include lung and heart doses, age, and carboplatin chemotherapy. These data also suggest that elderly patients may be more susceptible to lower doses of radiation to the lung. Based on these data, dose constraints to limit the risk of RP2+ to <5% in the setting of PORT include lungV5 ≤65% in patients <65 years old and lungV5 ≤36% in patients 65 years or older.

Dataset Information

Genetic variants of SP-D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy.

Background

Methods

Results

Conclusions

Publications

Genetic variants of SP-D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy.

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