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Genetic data improves survival prediction in patients with NSCLC, brain metastases
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The addition of EGFR and ALK gene alterations data to a prognostic tool may improve clinical decision-making and stratification of future clinical trials for patients with non–small-cell lung cancer and brain metastases, according to a multi-institutional retrospective database analysis published in JAMA Oncology.
The Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) — which includes four variables: patient age, Karnofsky Performance Status, extracranial metastases and number of brain metastases — was developed based on data derived from patients between 1985 and 2005.
The new index, called Lung-molGPA, incorporates genetic data.
“The updated Lung-molGPA incorporating gene alteration data into the DS-GPA is a user-friendly tool,” Paul W. Sperduto, MD, MPP, co-director of the Gamma Knife Center at University of Minnesota and medical director of Ridgeview Regional Radiation Oncology in Waconia, Minnesota, told HemOnc Today. These data also are scheduled for presentation at the Society of Neuro-Oncology Annual Meeting on Nov. 20, Sperduto said.
Although systemic therapies have improved OS for lung cancer — the leading cause of cancer-related deaths in the United States — lung cancer survivors face an increased risk for metastasis to the brain.
Sperduto and colleagues updated DS-GPA by incorporating more recently reported gene and molecular data on EGFR and ALK alterations for patients with NSCLC and brain metastases.
To develop the new index, researchers evaluated a retrospective database analysis of 2,186 patients diagnosed with NSCLC (adenocarcinoma, n = 1,521; nonadenocarcinoma, n = 665) and brain metastases between 2006 and 2014.
Survival outcomes served as the main targeted measure.
In the original study used to develop DS-GPA, patients studied had a median survival of 7 months from the time of initial treatment of brain metastases.
Under the new Lung-molGPA tool, Sperduto and colleagues introduced two additional factors, EGFR and ALK alterations in patients with adenocarcinoma — mutation status was not routinely tested for nonadenocarcinoma — in addition to the original four prognostic factors.
Median OS for patients in the new study was 12 months, which included 15.2 months for patients with adenocarcinoma and 9.2 months for patients with nonadenocarcinoma (P < .001).
Both tools scored patients from 0 to 4 based on the presence of these factors, with higher scores corresponding to better prognosis.
Only 4% (n = 65) of patients with adenocarcinoma NSCLC received Lung-molGPA scores of 3.5 to 4.0, but those patients had a median survival of 46.8 months.
Median survival among the original cohort of 161 (9%) of adenocarcinoma and nonadenocarcinoma patients with a score from 3.5 to 4 using DS-GPA was 14.8 months.
Researchers confirmed the original four factors were prognostic in patients with nonadenocarcinoma from the new cohort.
Because the data are retrospective with inherent selection bias, researchers noted they cannot be used to conclude that one treatment is better than another.
Considering biology and patient status will help increase the accuracy of prognoses for patients, John H. Suh, MD, chairman of the department of radiation oncology and associate director of the Gamma Knife Center at the Brain Tumor and Neuro-Oncology Center at Cleveland Clinic, wrote in an invited commentary.
“To improve the value and outcomes of available treatments, patients with poor prognoses, ie, low Lung-molGPA scores, should be offered different therapies than those with good prognoses, who will most likely benefit from the more expensive and aggressive treatment approaches,” Suh wrote.
“...Ultimately, we must move beyond prognostic factors and develop predictive markers of survival, quality of life, neurocognitive function and toxic effects that will further our understanding of brain metastases and aid in the development of personalized therapies that make a meaningful difference,” he added. – by Chuck Gormley
For more information:
Paul W. Sperduto , MD, MSS, can be reached at Gamma Knife Center, University of Minnesota, 560 S Maple St, Suite 10, Waconia, MN 55387; email: psperduto@mropa.com.
Disclosure: Sperduto reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures. Suh reports consulting and research support from Varian Medical Systems and travel support from Elekta.
Perspective
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Stephanie E. Weiss
This is a very important study for patients with lung cancer that has spread to the brain.
It has two immediate practical applications.
First, this index allows doctors to give more nuanced prognostic information to their patients with lung cancer spread to the brain. We used to believe that such a diagnosis heralded a survival of weeks to months. This study proves that for some patients, survival may be on the order of years, and we may now be able to identify such patients up front.
Second, more accurate prognostic tools allow us to better tailor and individualize discussions of the effectiveness and potential side effects of various treatment options, such as radiosurgery and whole brain radiation.
This study also contains other important worth mentioning.
It demonstrates that stage IV lung cancer today does not necessarily mean a dire prognosis. For some patients, it may be managed more like a chronic disease. Further, this study demonstrates that both the inherent biologic features of a particular cancer — such as the genetic expression — and patient factors, such as one’s overall health, have a bearing on survival. It is likely that continued research will lead to the discovery of further lung and other site-specific molecular prognostic markers.
Disclosure: Weiss reports no relevant financial disclosures.
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