Epigenome‐wide three‐way interaction study identifies a complex pattern between TRIM27 , KIAA0226 and smoking associated with overall survival of early‐stage NSCLC

Purpose Lung cancer, of which 85% is non–small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC. Patients and Methods One hundred early-stage NSCLC patients from Massachusetts General Hospital (MGH) were used as a discovery set and 89 NSCLC patients collected by the National Institute of Occupational Health, Norway, were used as a validation set. DNA was extracted from flash-frozen lung tissue with at least 70% tumor cellularity. Genome-wide genotyping was done using the high-density SNP chip. Copy numbers were inferred using median smoothing after intensity normalization. Cox models were used to screen and validate significant SNPs associated with the overall survival. Results Copy number gains in chromosomes 3q, 5p, and 8q were observed in both MGH and Norwegian cohorts. The top 50 SNPs associated with overall survival in the MGH cohort (P ≤ 2.5 × 10−4) were selected and examined using the Norwegian cohort. Five of the top 50 SNPs were validated in the Norwegian cohort with false discovery rate lower than 0.05 (P < .016) and all five were located in known genes: STK39, PCDH7, A2BP1, and EYA2. The numbers of risk alleles of the five SNPs showed a cumulative effect on overall survival (Ptrend = 3.80 × 10−12 and 2.48 × 10−7 for MGH and Norwegian cohorts, respectively). Conclusion Five SNPs were identified that may be prognostic of overall survival in early-stage NSCLC.

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Impact of Sarcopenia Using Normalized Total Psoas Area as a Surrogate on Overall Survival and Recurrence in Early Stage NSCLC Patients Treated with Stereotactic Body Radiotherapy

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2019.06.2446 ◽

2019 ◽

Vol 105 (1) ◽

pp. E535

Author(s):

J. Taylor ◽

A. David ◽

A.J. Song ◽

J. Guo ◽

B. Lu ◽

...

Keyword(s):

Overall Survival ◽

Stereotactic Body Radiotherapy ◽

Early Stage ◽

Early Stage Nsclc ◽

Nsclc Patients

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MA 13.06 New Risk Factors for Overall Survival After SBRT in Early Stage NSCLC: A Role of RT Plan Optimization

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.09.564 ◽

2017 ◽

Vol 12 (11) ◽

pp. S1853 ◽

Cited By ~ 1

Author(s):

F. Kong ◽

Y. Liu ◽

H. Zhang ◽

H. Yao ◽

A. Cerra-Franco ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Early Stage ◽

Early Stage Nsclc ◽

Plan Optimization

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Prolonged Overall Treatment Time Negatively Affects the Outcomes of Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: A Propensity Score-Weighted, Single-Center Analysis

10.21203/rs.3.rs-100183/v1 ◽

2020 ◽

Author(s):

TOSHIKI IKAWA ◽

Takahiro Tabuchi ◽

Koji Konishi ◽

Masahiro Morimoto ◽

Takero Hirata ◽

...

Keyword(s):

Overall Survival ◽

Propensity Score ◽

Local Control ◽

Treatment Time ◽

Early Stage ◽

Small Cell ◽

Tumor Control ◽

Small Cell Lung ◽

Overall Treatment Time ◽

Early Stage Nsclc

Abstract BackgroundPrevious studies have reported conflicting results for the effect of overall treatment time (OTT) on tumor control with stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). To examine this effect, we conducted a propensity score-weighted, retrospective, observational study at a single institution.MethodsWe analyzed the data of 200 patients with early-stage NSCLC who underwent SBRT (48 Gy in 4 fractions) at our institution between January 2007 and October 2013. Patients were grouped into consecutive (OTT = 4–5 days, n = 116) or non-consecutive treatment groups (OTT = 6–10 days, n = 84). The outcomes of interest were local control and overall survival. The Cox regression model was used with propensity score and inverse probability of treatment weighting.ResultsThe median OTTs in the consecutive and non-consecutive groups were 4 and 6 days, respectively. The 5-year local control and overall survival rates in the consecutive group vs. non-consecutive group were 86.3% vs. 77.2% and 55.5% vs. 51.8%, respectively. After propensity score-weighting, consecutive SBRT was associated with positive local control (adjusted hazard ratio 0.30, 95% confidence interval 0.14–0.65; p=0.002) and overall survival benefits (adjusted hazard ratio 0.56, 95% confidence interval 0.34–0.91; p=0.019). ConclusionsProlonged OTT negatively affected the outcomes of patients with early-stage NSCLC treated with SBRT. To our knowledge, this is the first study to show that in patients with early-stage NSCLC treated with the same dose-fractionation regimen, consecutive SBRT has a more beneficial effect on tumor control than does non-consecutive SBRT.

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Epigenetic–smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early‐stage NSCLC patients

Molecular Oncology ◽

10.1002/1878-0261.12785 ◽

2020 ◽

Vol 14 (11) ◽

pp. 2759-2774

Author(s):

Xinyu Ji ◽

Lijuan Lin ◽

Sipeng Shen ◽

Xuesi Dong ◽

Chao Chen ◽

...

Keyword(s):

Dna Methylation ◽

Overall Survival ◽

Early Stage ◽

Early Stage Nsclc ◽

Heterogeneous Effects ◽

Nsclc Patients ◽

Smoking Interaction

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Lung stereotactic body radiation therapy for elderly patients aged ≥ 80 years with pathologically proven early-stage non-small cell lung cancer: a retrospective cohort study

Radiation Oncology ◽

10.1186/s13014-021-01769-7 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Kenta Watanabe ◽

Kuniaki Katsui ◽

Soichiro Sugiyama ◽

Kotaro Yoshio ◽

Masahiro Kuroda ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Elderly Patients ◽

Stereotactic Body Radiation Therapy ◽

Radiation Pneumonitis ◽

Early Stage ◽

Small Cell ◽

Small Cell Lung ◽

Survival Curves ◽

Early Stage Nsclc

Abstract Background Stereotactic body radiation therapy (SBRT) is an established therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). Many elderly patients are medically inoperable owing to comorbidities. Therefore, SBRT may be a useful therapy for elderly patients. However, the application of SBRT for patients aged ≥ 80 years has not been completely elucidated. Therefore, this study aimed to assess the clinical utility of SBRT for elderly patients aged ≥ 80 years with pathologically proven early-stage NSCLC. Methods We retrospectively evaluated the data of patients aged ≥ 80 years with pathologically proven primary NSCLC who underwent SBRT at our institution between January 2009 and March 2020. Treatment outcomes and toxicities were analyzed. We used the Kaplan–Meier method to estimate survival curves and the log-rank test to compare the survival curves. We performed univariate and multivariate Cox regression analyses. p-values < 0.05 were regarded significant. Results Sixty-four patients (65 lesions) were included, and the median follow-up period was 38.7 (range 3.5–95.7) months. The median age was 82.9 (range 80.0–94.8) years. Sixteen patients were medically operable, and 48 patients were medically inoperable. The prescribed dose of SBRT was either 48 Gy in four fractions or 60 Gy in 10 fractions. The median survival time was 60.0 months (95% confidence interval, 43.5–71.1). The 1-, 3-, and 5-year local control, cancer-specific survival, progression-free survival, and overall survival rates were 98.4%, 98.4%, 81.0%, and 88.9%; 90.1%, 93.7%, 58.9%, and 68.3%; and 87.4%, 83.5%, 38.2%, and 47.5%, respectively. Multivariate analysis revealed that inoperability and solid nodules were the predictors of poor overall survival after SBRT in elderly patients. Two patients (3.1%) had grade 3 radiation pneumonitis, and one patient (1.6%) had grade 5 radiation pneumonitis. Conclusions SBRT was feasible in patients aged ≥ 80 years with NSCLC. It achieved good local control with minimal toxicity. SBRT may be beneficial in elderly patients with early-stage NSCLC.

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Stereotactic body radiotherapy for early-stage non-small cell lung cancer in patients with subclinical interstitial lung disease.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21050 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21050-e21050

Author(s):

Min Hu ◽

Xiaojiang Sun ◽

Yuanjun Liu ◽

Yaoyao Zhu ◽

Qinghua Xu ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Early Stage ◽

Survival Rates ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Free Survival ◽

Early Stage Nsclc ◽

Nsclc Patients

e21050 Background: Stereotactic body radiotherapy (SBRT) is a highly focused radiation treatment, which is now recommended to treat non-small cell lung cancer (NSCLC) patients with early stage disease. The purpose of this study is to evaluate the efficacy and toxicity of SBRT for early stage NSCLC patients with subclinical interstitial lung disease (ILD). Methods: One hundred and nine patients with early stage NSCLC were treated with SBRT between December 2011 and August 2016 in our institution; patients with subclinical (untreated and oxygen-free) ILD were treated with SBRT, while those with clinical ILD (post- or under treatment) were not. The median SBRT dose was 50 Gy in 5 fractions and the median biologically effective dose (BED; α/β = 10) was 100 Gy (range:72-119 Gy). The presence of subclinical ILD in the pre-SBRT CT findings was reviewed by two chest radiologists. The relationships among the efficacy, radiation pneumonitis (RP) and clinical factors were investigated. Results: Subclinical ILD was recognized in 38 (35%) of 109 patients. Grade 2–4 RP was recognized in 48 (44%) of 109 patients, no Grade 5 RP was happened. Grade 2–4 RP was observed in 17 (45%) of 38 patients with subclinical ILD. Subclinical ILD was not found to be a significant factor influencing Grade 2–4 RP; however, extensive RP beyond the irradiated field, including the contralateral lung, was recognized in only two patients who were both suffering from subclinical ILD, and the rate of extensive RP was significantly high in the patients with subclinical ILD. Dosimetric factors of the lungs (V5, V10, V20, MLD, V12.5, V13.5) were significantly associated with Grade 2–4 RP. The three-year overall survival and progression-free survival rates of all patients were 82.8% and 62.5%, respectively. No significant differences were seen in either overall survival or progression-free survival rates among the patients with ILD and those without ILD, or with RP and those without RP. Conclusions: Subclinical ILD was not found to be a significant factor for Grade 2–5 RP or clinical outcomes in early stage NSCLC treated with SBRT; however, uncommon extensive RP can occur in patients with subclinical ILD.

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