Predictors of Nodal and Metastatic Failure in Early Stage Non–small-cell Lung Cancer After Stereotactic Body Radiation Therapy

Alberto Cerra-Franco, Sheng Liu, Michella Azar, Kevin Shiue, Samantha Freije, Jason Hinton, Christopher R. Deig, Donna Edwards, Neil C. Estabrook, Susannah G. Ellsworth, Ke Huang, Khalil Diab, Mark Langer, Richard Zellars, Feng Ming Kong, Jun Wan, Tim Lautenschlaeger

Research output: Contribution to journalArticle

Abstract

Introduction/Background: Many patients with early stage non–small-cell lung cancer (ES-NSCLC) undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. Materials and Methods: We included 363 patients with ES-NSCLC who received SBRT; the median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): gender; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. Results: A total of 111 (27.3%) of 406 lesions metastasized. GTV and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (P <.001 and hazard ratio [HR], 1.02 per mL; P <.05 and HR, 0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV and prescription dose was built: risk score = (0.01611 × GTV) − (0.00525 × dose [BED10]). Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk score identified significant differences in time to metastases between low-, medium-, and high-risk patients (P <.001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. Conclusion: GTV and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT.

Original languageEnglish (US)
JournalClinical Lung Cancer
DOIs
StateAccepted/In press - Jan 1 2019

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Non-Small Cell Lung Carcinoma
Radiotherapy
Neoplasm Metastasis
Tumor Burden
Lung
Histology
Proportional Hazards Models
Prescriptions
Linear Models
Smoking
Radiation

Keywords

  • Metastasis
  • SABR
  • SBRT
  • Stereotactic body ablative radiotherapy
  • Stereotactic body radiation therapy

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Predictors of Nodal and Metastatic Failure in Early Stage Non–small-cell Lung Cancer After Stereotactic Body Radiation Therapy. / Cerra-Franco, Alberto; Liu, Sheng; Azar, Michella; Shiue, Kevin; Freije, Samantha; Hinton, Jason; Deig, Christopher R.; Edwards, Donna; Estabrook, Neil C.; Ellsworth, Susannah G.; Huang, Ke; Diab, Khalil; Langer, Mark; Zellars, Richard; Kong, Feng Ming; Wan, Jun; Lautenschlaeger, Tim.

In: Clinical Lung Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Cerra-Franco, A, Liu, S, Azar, M, Shiue, K, Freije, S, Hinton, J, Deig, CR, Edwards, D, Estabrook, NC, Ellsworth, SG, Huang, K, Diab, K, Langer, M, Zellars, R, Kong, FM, Wan, J & Lautenschlaeger, T 2019, 'Predictors of Nodal and Metastatic Failure in Early Stage Non–small-cell Lung Cancer After Stereotactic Body Radiation Therapy', Clinical Lung Cancer. https://doi.org/10.1016/j.cllc.2018.12.016
Cerra-Franco, Alberto ; Liu, Sheng ; Azar, Michella ; Shiue, Kevin ; Freije, Samantha ; Hinton, Jason ; Deig, Christopher R. ; Edwards, Donna ; Estabrook, Neil C. ; Ellsworth, Susannah G. ; Huang, Ke ; Diab, Khalil ; Langer, Mark ; Zellars, Richard ; Kong, Feng Ming ; Wan, Jun ; Lautenschlaeger, Tim. / Predictors of Nodal and Metastatic Failure in Early Stage Non–small-cell Lung Cancer After Stereotactic Body Radiation Therapy. In: Clinical Lung Cancer. 2019.
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abstract = "Introduction/Background: Many patients with early stage non–small-cell lung cancer (ES-NSCLC) undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. Materials and Methods: We included 363 patients with ES-NSCLC who received SBRT; the median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): gender; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. Results: A total of 111 (27.3{\%}) of 406 lesions metastasized. GTV and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (P <.001 and hazard ratio [HR], 1.02 per mL; P <.05 and HR, 0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV and prescription dose was built: risk score = (0.01611 × GTV) − (0.00525 × dose [BED10]). Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk score identified significant differences in time to metastases between low-, medium-, and high-risk patients (P <.001), with 3-year estimates of 81.1{\%}, 63.8{\%}, and 38{\%}, respectively. Conclusion: GTV and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT.",
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T1 - Predictors of Nodal and Metastatic Failure in Early Stage Non–small-cell Lung Cancer After Stereotactic Body Radiation Therapy

AU - Cerra-Franco, Alberto

AU - Liu, Sheng

AU - Azar, Michella

AU - Shiue, Kevin

AU - Freije, Samantha

AU - Hinton, Jason

AU - Deig, Christopher R.

AU - Edwards, Donna

AU - Estabrook, Neil C.

AU - Ellsworth, Susannah G.

AU - Huang, Ke

AU - Diab, Khalil

AU - Langer, Mark

AU - Zellars, Richard

AU - Kong, Feng Ming

AU - Wan, Jun

AU - Lautenschlaeger, Tim

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Introduction/Background: Many patients with early stage non–small-cell lung cancer (ES-NSCLC) undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. Materials and Methods: We included 363 patients with ES-NSCLC who received SBRT; the median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): gender; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. Results: A total of 111 (27.3%) of 406 lesions metastasized. GTV and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (P <.001 and hazard ratio [HR], 1.02 per mL; P <.05 and HR, 0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV and prescription dose was built: risk score = (0.01611 × GTV) − (0.00525 × dose [BED10]). Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk score identified significant differences in time to metastases between low-, medium-, and high-risk patients (P <.001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. Conclusion: GTV and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT.

AB - Introduction/Background: Many patients with early stage non–small-cell lung cancer (ES-NSCLC) undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. Materials and Methods: We included 363 patients with ES-NSCLC who received SBRT; the median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): gender; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. Results: A total of 111 (27.3%) of 406 lesions metastasized. GTV and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (P <.001 and hazard ratio [HR], 1.02 per mL; P <.05 and HR, 0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV and prescription dose was built: risk score = (0.01611 × GTV) − (0.00525 × dose [BED10]). Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk score identified significant differences in time to metastases between low-, medium-, and high-risk patients (P <.001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. Conclusion: GTV and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT.

KW - Metastasis

KW - SABR

KW - SBRT

KW - Stereotactic body ablative radiotherapy

KW - Stereotactic body radiation therapy

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