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Multicenter Study
. 2017 Jun 1;3(6):827-831.
doi: 10.1001/jamaoncol.2016.3834.

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  1 , T Jonathan Yang  2 , Kathryn Beal  2 , Hubert Pan  3 , Paul D Brown  3 , Ananta Bangdiwala  4 , Ryan Shanley  4 , Norman Yeh  5 , Laurie E Gaspar  5 , Steve Braunstein  6 , Penny Sneed  6 , John Boyle  7 , John P Kirkpatrick  7 , Kimberley S Mak  8 , Helen A Shih  8 , Alex Engelman  9 , David Roberge  10 , Nils D Arvold  11 , Brian Alexander  11 , Mark M Awad  12 , Joseph Contessa  12 , Veronica Chiang  12 , John Hardie  13 , Daniel Ma  13 , Emil Lou  14 , William Sperduto  7 , Minesh P Mehta  9
Affiliations
Multicenter Study

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 et al. JAMA Oncol. .

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-molGPA.

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-molGPA, 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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Conflict of interest statement

Conflict of Interest Disclosures: The following authors have served as consultants on other topics unrelated to the present work: Dr Kirkpatrick (Varian), Dr Shih (Genentech), Dr Roberge (Varian, Siemens, Accuray, BrainLab, Elekta), Dr Alexander (Abbvie, Precision Health Economics, Amgen), and Dr Mehta (Abbott, Novelos, Phillips, BMS, Celldex, Roche, Elekta, Novocure, Novartis, Cavion, Pharmacyclics). No other conflicts are reported.

Figures

Figure.
Figure.. Kaplan-Meier Curves Showing Survival by the Lung-molGPA for Non–Small-Cell Lung Cancer
GPA indicates graded prognostic assessment.
See this image and copyright information in PMC

Comment in

References

    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108. - PubMed
    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30. - PubMed
    1. Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol. 2005;75(1):5-14. - PubMed
    1. Park DM, Posner JB. Management of intracranial metastases: history In: Sawaya R, ed. Intracranial Metastases: Current Management Strategies. Oxford, England: Blackwell Publishing Ltd; 2004:3-19.
    1. Rosell R, Carcereny E, Gervais R, et al. ; Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica . Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239-246. - PubMed

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