As Lung Cancer Survival Evolves, So Does a Prognostic Tool

Nick Mulcahy

November 21, 2016

Among lung cancer patients with brain metastases, survival has improved significantly in the past 2 decades ― as has clinicians' ability to estimate that survival, say the authors of a new study on the subject.

As a result, an important prognostic tool, the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA), has needed updating, explain the investigators, led by Paul Sperduto, MD, a radiation oncologist at the University of Minnesota Gamma Knife Center in Minneapolis.

The new study from the team provides the details on the updating of the DS-GPA, which is used for patients with non–small cell lung cancer (NSCLC) and brain metastases. The study also reveals what the researchers newly learned about the evolving lengths of survival in this setting.

The study was published online November 17 in JAMA Oncology and was reported at the Society of Neuro-Oncology annual meeting in Phoenix, Arizona, on November 20.

"In the past, conventional wisdom was that all patients with brain metastases died within 3 to 6 months. Now we know the median survival for some of these patients (ALK-positive) is nearly 4 years," said Dr Sperduto in a press statement.

Dr Paul Sperduto

The new tool, known as the Lung Graded Prognostic Assessment (Lung-molGPA), now incorporates data from patients with genetic alterations who have better survival. The tool is a free smartphone/online app that is available at brainmetgpa.com.

The ramifications of the new tool in the clinic are significant, suggested Dr Sperduto.

"Having a more accurate estimate of survival will affect patients' and doctors' choices about how they wish to spend their time and what treatments are most appropriate," he said.

There is a substantial need for better prognostics in cancer patients with brain metastases, says John Suh, MD, a radiation oncologist at the Taussig Cancer Institute of the Cleveland Clinic in Ohio, in an accompanying editorial.

Dr Suh points out that a recent survey of clinicians found that 45% and 18% of their predictions inaccurately estimated survival in a sample of 150 cancer patients by more than 6 months and more than 12 months, respectively (J Neurosurg. 2014;120:24-30). The surveyed physicians used older prognostic tools along with clinical, radiologic, and primary tumor data in making their predictions.

Dr Suh was also blunt about what should be done with patients whose Lung-molGPAs scores are low and who therefore have a poor prognosis.

"To improve the value and outcomes of available treatments, patients with poor prognosis...should be offered different therapies than those with good prognosis, who will most likely benefit from the more expensive and aggressive treatment approaches," he writes.

The original DS-GPA was based on four factors found in 1833 patients with NSCLC and brain metastases diagnosed between 1985 and 2005: patient age, Karnofsky Performance Status score, extracranial metastases, and number of brain metastases.

Notably, the patients studied for the creation of the first DS-GPA had a median survival of 7 months from the time of initial treatment of brain metastases. Overall, the median survival ranged from 3.0 to 14.8 months, depending on the status of the factors, or "prognostic class."

To design the updated Lung-molGPA, the team analyzed data from 2186 patients from 2006 through 2014 with NSCLC and newly diagnosed brain metastases (1521 adenocarcinoma and 665 nonadenocarcinoma).

The authors note that the analysis is the largest study of lung cancer patients with brain metastases ever reported.

They also note that the type of treatment the patients underwent was not considered because the purpose of a prognostic index is to estimate survival prior to treatment.

The team found that significant prognostic factors for these patients included the original four factors from the DS-GPA index plus two new ones: EGFR and ALK alterations in patients with adenocarcinoma (mutation status is not routinely tested for nonadenocarcinoma and therefore was not relevant in the other group of patients).

Importantly, the overall median survival for the cohort in the present study was 12 months; those patients with NSCLC-adenocarcinoma and higher Lung-molGPA scores (3.5 to 4.0) had a median survival of nearly 4 years. Overall, with the updated Lung-molGPA, median survival ranged from 3.0 to 46.8 months.

Dr Sperduto noted that higher Lung-molGPA scores are desirable. "Just like a grade point average [GPA], this GPA is also on a scale of 0 to 4, where 0 corresponds to the worst prognosis and 4, the best," he told Medscape Medical News.

Dr Sperduto and his colleagues also reported that in the new study, the overall median survival rates for patients with adenocarcinoma (15.2 months) and those without nonadenocarcinoma (9.2 months) were significantly different (P < .001).

An expert not involved with the study said that the Lung-molGPA represents the way forward in oncology.

"This study is important, as it represents the next wave of prognostic tools that incorporate biomarkers into the prediction tool. As we learn more and improve molecular profiling, prior prognostic tools will increasingly become irrelevant," said Arjun Sahgal, MD, a radiation oncologist at the University of Toronto and Sunnybrook Health Sciences Center, in Canada.

Dr Sahgal told Medscape Medical News that oncology is now in the "era of aggressively managing patients with [brain] metastases." But he said that it is important to be "selective" about who undergoes treatments such as stereotactic radiation and surgery because they "are not without adverse events and are expensive to the healthcare system."

Dr Speduto provided a case study to illustrate the impact of the new Lung-molGPA.

He described a 68-year-old female patient with lung adenocarcinoma who had minimal symptoms (Karnofsky Performance Status score of 90) and no evidence of extracranial metastases. She presented with headaches and was found to have four brain metastases.

"The patient comes in with family and grandchildren. One grandchild is getting married next year and another is graduating in 2 years, and they want to know if grandma will be at those important life events," he said.

In the past, this patient, like all patients with brain metastases, would have been told that the median survival for patients such as her was 6 months, observed Dr Sperduto.

But, by using the Lung-molGPA, her physician will answer the simple questions from the app (including those about the presence of any gene alterations) and "learn that her Lung-molGPA score is 4.0," which has a projected median survival of 46.8 months. "This information will affect how the patient and family choose to spend their time and will assist the patient and her doctors in determining which treatments are most appropriate," he commented.

In patients who have NSCLC that is EGFR mutation–positive, systemic therapies for lung cancer now include drugs such as erlotinib (Tarceva, Osi), gefitinib (Iressa, AstraZeneca), and afatinib (Gilotrif, Boehringer Ingelheim), whereas patients who have tumors that are positive for the ALK rearrangement can be treated with crizotinib (Xalkori, Pfizer), alectinib (Alecensa, Genentech), or ceritinib (Zykadia, Novartis).

Lung-molGPA also can be useful in clinical trials, say study author Dr Sperduto and editorialist Dr Suh. Both comment that it will allow for the development of clinical trials that can stratify, select, and randomly assigned patients on the basis of more accurate prognostic criteria and thus ensure that the studies are comparing groups of patients with similar prognoses.

Study funding was provided by the National Institutes of Health and the National Center for Advancing Translational Sciences. Several authors have financial ties to industry, all of which were unrelated to the present study. Dr Suh has financial ties to Varian Medical Systems and Elekta. Dr Sahgal has financial relationships with Medtronic and Elekta.

JAMA Oncol. Published online November 17, 2016. Full text, Editorial

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick

For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc

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