Graded Prognostic Assessment (GPA) for Patients With Lung Cancer and Brain Metastases: Initial Report of the Small Cell Lung Cancer GPA and Update of the Non-Small Cell Lung Cancer GPA Including the Effect of Programmed Death Ligand 1 and Other Prognostic Factors

Paul W. Sperduto, Brian De, Jing Li, David Carpenter, John Kirkpatrick, Michael Milligan, Helen A. Shih, Tugce Kutuk, Rupesh Kotecha, Hajime Higaki, Manami Otsuka, Hidefumi Aoyama, Malie Bourgoin, David Roberge, Salah Dajani, Sean Sachdev, Jordan Gainey, John M. Buatti, William Breen, Paul D. BrownLisa Ni, Steve Braunstein, Matthew Gallitto, Tony J.C. Wang, Ryan Shanley, Emil Lou, Jay Shiao, Laurie E. Gaspar, Satoshi Tanabe, Toshimichi Nakano, Yi An, Veronica Chiang, Liang Zeng, Hany Soliman, Hesham Elhalawani, Daniel Cagney, Evan Thomas, Drexell H. Boggs, Manmeet S. Ahluwalia, Minesh P. Mehta

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PURPOSE: Patients with lung cancer and brain metastases represent a markedly heterogeneous population. Accurate prognosis is essential to optimally individualize care. In prior publications, we described the graded prognostic assessment (GPA), but a GPA for patients with small cell lung cancer (SCLC) has never been reported, and in non-small cell lung cancer (NSCLC), the effect of programmed death ligand 1 (PD-L1) was unknown. The 3-fold purpose of this work is to provide the initial report of an SCLC GPA, to evaluate the effect of PD-L1 on survival in patients with NSCLC, and to update the Lung GPA accordingly.

METHODS AND MATERIALS: A multivariable analysis of prognostic factors and treatments associated with survival was performed on 4183 patients with lung cancer (3002 adenocarcinoma, 611 nonadenocarcinoma, 570 SCLC) with newly diagnosed brain metastases between January 1, 2015, and December 31, 2020, using a multi-institutional retrospective database. Significant variables were used to update the Lung GPA.

RESULTS: Overall median survival for lung adenocarcinoma, SCLC, and nonadenocarcinoma was 17, 10, and 8 months, respectively, but varied widely by GPA from 2 to 52 months. In SCLC, the significant prognostic factors were age, performance status, extracranial metastases, and number of brain metastases. In NSCLC, the distribution of molecular markers among patients with lung adenocarcinoma and known primary tumor molecular status revealed alterations/expression in PD-L1 50% to 100%, PD-L1 1% to 49%, epidermal growth factor receptor, and anaplastic lymphoma kinase in 32%, 31%, 30%, and 7%, respectively. Median survival of patients with lung adenocarcinoma and brain metastases with 0, 1% to 49%, and ≥50% PD-L1 expression was 17, 19, and 24 months, respectively (P < .01), confirming PD-L1 is a prognostic factor. Previously identified prognostic factors for NSCLC (epidermal growth factor receptor and anaplastic lymphoma kinase status, performance status, age, number of brain metastases, and extracranial metastases) were reaffirmed. These factors were incorporated into the updated Lung GPA with robust separation between subgroups for all histologies.

CONCLUSIONS: Survival for patients with lung cancer and brain metastases has improved but varies widely. The initial report of a GPA for SCLC is presented. For patients with NSCLC-adenocarcinoma and brain metastases, PD-L1 is a newly identified significant prognostic factor, and the previously identified factors were reaffirmed. The updated indices establish unique criteria for SCLC, NSCLC-nonadenocarcinoma, and NSCLC-adenocarcinoma (incorporating PD-L1). The updated Lung GPA, available for free at, provides an accurate tool to estimate survival, individualize treatment, and stratify clinical trials.

Original languageEnglish (US)
Pages (from-to)60-74
Number of pages15
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number1
StatePublished - Sep 1 2022

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health (NIH) grant UL1TR002494 from the National Center for Advancing Translational Sciences (NCATS). Study data were collected and managed using Research Electronic Data Capture electronic data capture tools hosted at the University of Minnesota. This study was also supported by NIH grant P30 CA77598 using the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota, and the NCATS. The design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication were solely the responsibility of the authors and do not necessarily represent the official views of the funders. No author received support for the work described in this article other than R.S. for statistical analyses.

Publisher Copyright:
© 2022 Elsevier Inc.


  • Adenocarcinoma
  • Adenocarcinoma of Lung
  • Anaplastic Lymphoma Kinase
  • B7-H1 Antigen
  • Brain Neoplasms/secondary
  • Carcinoma, Non-Small-Cell Lung/pathology
  • ErbB Receptors
  • Humans
  • Lung Neoplasms/pathology
  • Prognosis
  • Retrospective Studies
  • Small Cell Lung Carcinoma

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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