Estimating survival in patients with lung cancer and brain metastases an update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA)

Paul W. Sperduto, T. Jonathan Yang, Kathryn Beal, Hubert Pan, Paul D. Brown, Ananta Bangdiwala, Ryan Shanley, Norman Yeh, Laurie E. Gaspar, Steve Braunstein, Penny Sneed, John Boyle, John P. Kirkpatrick, Kimberley S. Mak, Helen A. Shih, Alex Engelman, David Roberge, Nils D. Arvold, Brian Alexander, Mark M. AwadJoseph Contessa, Veronica Chiang, John Hardie, Daniel Ma, Emil Lou, William Sperduto, Minesh P. Mehta

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

IMPORTANCE: Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. As systemic therapies improve, patients with lung cancer live longer and thus are at increased risk for brain metastases. Understanding how prognosis varies across this heterogeneous patient population is essential to individualize care and design future clinical trials. OBJECTIVE: To update the current Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with non-small-cell lung cancer (NSCLC) and brain metastases. The DS-GPA is based on data from patients diagnosed between 1985 and 2005, and we set out to update it by incorporating more recently reported gene and molecular alteration data for patients with NSCLC and brain metastases. This new index is called the Lung-mol GPA. DESIGN, SETTING, AND PARTICIPANTS: This is a multi-institutional retrospective database analysis of 2186 patients diagnosed between 2006 and 2014 with NSCLC and newly diagnosed brain metastases. The multivariable analyses took place between December 2015 and May 2016, and all prognostic factors were weighted for significance by hazard ratios. Significant factors were included in the updated Lung-molGPA prognostic index. MAIN OUTCOMES AND MEASURES The main outcome was survival. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. Log rank tests were used to compare adjacent classes and to compare overall survival for adenocarcinoma vs nonadenocarcinoma groups. RESULTS: The original DS-GPA was based on 4 factors found in 1833 patients with NSCLC and brain metastases diagnosed between 1985 and 2005: patient age, Karnofsky Performance Status, extracranial metastases, and number of brain metastases. The patients studied for the creation of the DS-GPA had a median survival of 7 months from the time of initial treatment of brain metastases. To design the updated Lung-mol GPA, we analyzed data from 2186 patients from 2006 through 2014 with NSCLC and newly diagnosed brain metastases (1521 adenocarcinoma and 665 nonadenocarcinoma). Significant prognostic factors included the original 4 factors used in the DS-GPA index plus 2 new factors: EGFR and ALK alterations in patients with adenocarcinoma (mutation status was not routinely tested for nonadenocarcinoma). The overall median survival for the cohort in the present study was 12 months, and those with NSCLC-adenocarcinoma and Lung-molGPA scores of 3.5 to 4.0 had a median survival of nearly 4 years. CONCLUSIONS AND RELEVANCE: In recent years, patient survival and physicians' ability to predict survival in NSCLC with brain metastases has improved significantly. The updated Lung-molGPA incorporating gene alteration data into the DS-GPA is a user-friendly tool that may facilitate clinical decision making and appropriate stratification of future clinical trials.

Original languageEnglish (US)
Pages (from-to)827-831
Number of pages5
JournalJAMA oncology
Volume3
Issue number6
DOIs
StatePublished - Jun 1 2017

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Brain Neoplasms
Lung Neoplasms
Neoplasm Metastasis
Lung
Survival
Non-Small Cell Lung Carcinoma
Brain
Adenocarcinoma
Clinical Trials
Karnofsky Performance Status
Genes
Databases
Physicians
Weights and Measures
Mutation
Mortality

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Estimating survival in patients with lung cancer and brain metastases an update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA). / Sperduto, Paul W.; Yang, T. Jonathan; Beal, Kathryn; Pan, Hubert; Brown, Paul D.; Bangdiwala, Ananta; Shanley, Ryan; Yeh, Norman; Gaspar, Laurie E.; Braunstein, Steve; Sneed, Penny; Boyle, John; Kirkpatrick, John P.; Mak, Kimberley S.; Shih, Helen A.; Engelman, Alex; Roberge, David; Arvold, Nils D.; Alexander, Brian; Awad, Mark M.; Contessa, Joseph; Chiang, Veronica; Hardie, John; Ma, Daniel; Lou, Emil; Sperduto, William; Mehta, Minesh P.

In: JAMA oncology, Vol. 3, No. 6, 01.06.2017, p. 827-831.

Research output: Contribution to journalArticle

Sperduto, PW, Yang, TJ, Beal, K, Pan, H, Brown, PD, Bangdiwala, A, Shanley, R, Yeh, N, Gaspar, LE, Braunstein, S, Sneed, P, Boyle, J, Kirkpatrick, JP, Mak, KS, Shih, HA, Engelman, A, Roberge, D, Arvold, ND, Alexander, B, Awad, MM, Contessa, J, Chiang, V, Hardie, J, Ma, D, Lou, E, Sperduto, W & Mehta, MP 2017, 'Estimating survival in patients with lung cancer and brain metastases an update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA)', JAMA oncology, vol. 3, no. 6, pp. 827-831. https://doi.org/10.1001/jamaoncol.2016.3834
Sperduto, Paul W. ; Yang, T. Jonathan ; Beal, Kathryn ; Pan, Hubert ; Brown, Paul D. ; Bangdiwala, Ananta ; Shanley, Ryan ; Yeh, Norman ; Gaspar, Laurie E. ; Braunstein, Steve ; Sneed, Penny ; Boyle, John ; Kirkpatrick, John P. ; Mak, Kimberley S. ; Shih, Helen A. ; Engelman, Alex ; Roberge, David ; Arvold, Nils D. ; Alexander, Brian ; Awad, Mark M. ; Contessa, Joseph ; Chiang, Veronica ; Hardie, John ; Ma, Daniel ; Lou, Emil ; Sperduto, William ; Mehta, Minesh P. / Estimating survival in patients with lung cancer and brain metastases an update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA). In: JAMA oncology. 2017 ; Vol. 3, No. 6. pp. 827-831.
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T1 - Estimating survival in patients with lung cancer and brain metastases an update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA)

AU - Sperduto, Paul W.

AU - Yang, T. Jonathan

AU - Beal, Kathryn

AU - Pan, Hubert

AU - Brown, Paul D.

AU - Bangdiwala, Ananta

AU - Shanley, Ryan

AU - Yeh, Norman

AU - Gaspar, Laurie E.

AU - Braunstein, Steve

AU - Sneed, Penny

AU - Boyle, John

AU - Kirkpatrick, John P.

AU - Mak, Kimberley S.

AU - Shih, Helen A.

AU - Engelman, Alex

AU - Roberge, David

AU - Arvold, Nils D.

AU - Alexander, Brian

AU - Awad, Mark M.

AU - Contessa, Joseph

AU - Chiang, Veronica

AU - Hardie, John

AU - Ma, Daniel

AU - Lou, Emil

AU - Sperduto, William

AU - Mehta, Minesh P.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - IMPORTANCE: Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. As systemic therapies improve, patients with lung cancer live longer and thus are at increased risk for brain metastases. Understanding how prognosis varies across this heterogeneous patient population is essential to individualize care and design future clinical trials. OBJECTIVE: To update the current Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with non-small-cell lung cancer (NSCLC) and brain metastases. The DS-GPA is based on data from patients diagnosed between 1985 and 2005, and we set out to update it by incorporating more recently reported gene and molecular alteration data for patients with NSCLC and brain metastases. This new index is called the Lung-mol GPA. DESIGN, SETTING, AND PARTICIPANTS: This is a multi-institutional retrospective database analysis of 2186 patients diagnosed between 2006 and 2014 with NSCLC and newly diagnosed brain metastases. The multivariable analyses took place between December 2015 and May 2016, and all prognostic factors were weighted for significance by hazard ratios. Significant factors were included in the updated Lung-molGPA prognostic index. MAIN OUTCOMES AND MEASURES The main outcome was survival. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. Log rank tests were used to compare adjacent classes and to compare overall survival for adenocarcinoma vs nonadenocarcinoma groups. RESULTS: The original DS-GPA was based on 4 factors found in 1833 patients with NSCLC and brain metastases diagnosed between 1985 and 2005: patient age, Karnofsky Performance Status, extracranial metastases, and number of brain metastases. The patients studied for the creation of the DS-GPA had a median survival of 7 months from the time of initial treatment of brain metastases. To design the updated Lung-mol GPA, we analyzed data from 2186 patients from 2006 through 2014 with NSCLC and newly diagnosed brain metastases (1521 adenocarcinoma and 665 nonadenocarcinoma). Significant prognostic factors included the original 4 factors used in the DS-GPA index plus 2 new factors: EGFR and ALK alterations in patients with adenocarcinoma (mutation status was not routinely tested for nonadenocarcinoma). The overall median survival for the cohort in the present study was 12 months, and those with NSCLC-adenocarcinoma and Lung-molGPA scores of 3.5 to 4.0 had a median survival of nearly 4 years. CONCLUSIONS AND RELEVANCE: In recent years, patient survival and physicians' ability to predict survival in NSCLC with brain metastases has improved significantly. The updated Lung-molGPA incorporating gene alteration data into the DS-GPA is a user-friendly tool that may facilitate clinical decision making and appropriate stratification of future clinical trials.

AB - IMPORTANCE: Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. As systemic therapies improve, patients with lung cancer live longer and thus are at increased risk for brain metastases. Understanding how prognosis varies across this heterogeneous patient population is essential to individualize care and design future clinical trials. OBJECTIVE: To update the current Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with non-small-cell lung cancer (NSCLC) and brain metastases. The DS-GPA is based on data from patients diagnosed between 1985 and 2005, and we set out to update it by incorporating more recently reported gene and molecular alteration data for patients with NSCLC and brain metastases. This new index is called the Lung-mol GPA. DESIGN, SETTING, AND PARTICIPANTS: This is a multi-institutional retrospective database analysis of 2186 patients diagnosed between 2006 and 2014 with NSCLC and newly diagnosed brain metastases. The multivariable analyses took place between December 2015 and May 2016, and all prognostic factors were weighted for significance by hazard ratios. Significant factors were included in the updated Lung-molGPA prognostic index. MAIN OUTCOMES AND MEASURES The main outcome was survival. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. Log rank tests were used to compare adjacent classes and to compare overall survival for adenocarcinoma vs nonadenocarcinoma groups. RESULTS: The original DS-GPA was based on 4 factors found in 1833 patients with NSCLC and brain metastases diagnosed between 1985 and 2005: patient age, Karnofsky Performance Status, extracranial metastases, and number of brain metastases. The patients studied for the creation of the DS-GPA had a median survival of 7 months from the time of initial treatment of brain metastases. To design the updated Lung-mol GPA, we analyzed data from 2186 patients from 2006 through 2014 with NSCLC and newly diagnosed brain metastases (1521 adenocarcinoma and 665 nonadenocarcinoma). Significant prognostic factors included the original 4 factors used in the DS-GPA index plus 2 new factors: EGFR and ALK alterations in patients with adenocarcinoma (mutation status was not routinely tested for nonadenocarcinoma). The overall median survival for the cohort in the present study was 12 months, and those with NSCLC-adenocarcinoma and Lung-molGPA scores of 3.5 to 4.0 had a median survival of nearly 4 years. CONCLUSIONS AND RELEVANCE: In recent years, patient survival and physicians' ability to predict survival in NSCLC with brain metastases has improved significantly. The updated Lung-molGPA incorporating gene alteration data into the DS-GPA is a user-friendly tool that may facilitate clinical decision making and appropriate stratification of future clinical trials.

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