Our study’s novel finding is that the status of extracranial disease at the time of SRS treatment predicts more strongly than any other clinical or demographic variable for DIF. As a result, it may be possible to more effectively and prospectively identify patients who are most or least likely to have their intracranial disease entirely controlled by SRS alone. This criterion could significantly impact patient care by optimally selecting patients for SRS alone, while limiting the likelihood of needing salvage therapy.
Stereotactic radiosurgery (SRS) is increasingly being used for patients with brain metastases. Debate continues as to whether SRS is an appropriate first-line treatment without the additional use of surgery or whole brain radiation therapy (WBRT), and which endpoints, including OS, LC, DIF, and QOL are the most significant in this patient population [16, 22]. Limited data have demonstrated that in selected patients, an initial approach that includes SRS alone is appropriate [11, 16]. However, these data are tempered by the fact that in clinical practice, many patients do not fit these trial criteria, including those of advanced age, with progressive extracranial disease, and/or poor performance status. As a result, many gaps remain in the literature regarding patient outcomes when using SRS alone as an initial approach. At the same time, the enthusiasm for embarking on SRS alone as initial therapy is necessarily tempered by the risks of development of distant intracranial disease, including risks of neurocognitive decline related to disease progression [14, 23]. Although patient-reported outcomes (PROs)/QOL have not been studied among many subgroups of patients with brain metastases, it is also possible that an initial approach with SRS alone may lead to improved PROs/QOL for some who avoid or asymptomatically delay further intracranial treatment, while impaired long-term PROs/QOL for others who experience recurrence and require salvage therapy in the setting of pre-existing increase in symptoms. As a result, identification of factors predictive of distant intracranial recurrence is essential to refining patient selection for SRS, WBRT, or combination therapy.
Predicting survival of patients with brain metastases also has clinical utility. The first historical system developed for estimating patient prognosis, primarily during an era where treatment included WBRT and/or surgery, were the Recursive Partitioning Analysis (RPA) classes . These classes, separating patients based upon age, status of primary tumor, and performance status, created rough prognostic groupings that, while useful, left large, heterogeneous groups of patients within the same category. For example, in our study, 76% of patients were considered RPA class II. A more modern system, the Diagnosis-Specific Graded Prognostic Index (DS-GPA), incorporates age, KPS, presence of extracranial metastases, and number of brain metastases to develop a score predictive of survival . However, in our series, the DS-GPA was not found to be significantly associated with survival, suggesting that there still exists significant heterogeneity, even among patients within similar prognostic groups. Even more interestingly, the majority (68%) of the patients in this study had DS-GPA scores between 1.5-2.5, which would result in a projected median survival of 6.53 months. Instead, we have demonstrated prolonged survival of over 10 months in this carefully selected patient group, which underscores the importance of considering patients’ longer-term quality of life if they have limited brain metastases, even in the setting of additional adverse prognostic factors.
Although the present study has significant findings regarding survival and DIF, it does have several limitations due to its retrospective nature. Radiographic follow-up did not occur at consistent intervals for the entire study population, so events relating to LC and DIF may have been discovered, in some patients, with lag-time between development of disease and its recognition. The sample size of this study is still relatively small, and all power calculations were completed post-hoc due to the retrospective data collection and analysis. Additionally, no prospective quality of life measures or patient-reported outcomes were included in this study, which are of paramount importance in the palliative setting. Finally, patients were permitted to have additional systemic or local therapies at the discretion of their physicians, and preceding, concurrent, or adjuvant chemotherapy may have impacted DIF and OS in ways that were not analyzed in this study.