Whole-Brain Radiotherapy vs. Localized Radiotherapy after Resection of Brain Metastases in the Era of Targeted Therapy: A Retrospective Study

Abstract

Whether targeted therapy (TT) and radiotherapy impact survival after resection of brain metastases (BM) is unknown. The purpose of this study was to analyze the factors affecting overall survival (OS), local control (LC), distant control (DC), and leptomeningeal metastases (LMM) in patients who had undergone resection of BM. We retrospectively analyzed 124 consecutive patients who had undergone resection of BM between 2004 and 2020. Patient information about age, sex, Karnofsky Performance Scale (KPS), origin of cancer, synchronicity, tumor size, status of primary cancer, use of TT, extent of resection, and postoperative radiotherapy was collected. Radiation therapy was categorized into whole-brain radiotherapy (WBRT), localized radiotherapy (local brain radiotherapy or stereotactic radiosurgery (LBRT/SRS)), and no radiation. We identified factors that affect OS, LC, DC, and LMM. In multivariable analysis, significant factors for OS were higher KPS score (≥90) (HR 0.53, p = 0.011), use of TT (HR 0.43, p = 0.001), controlled primary disease (HR 0.63, p = 0.047), and single BM (HR 0.55, p = 0.016). Significant factors for LC were gross total resection (HR 0.29, p = 0.014) and origin of cancer (p = 0.041). Both WBRT and LBRT/SRS showed superior LC than no radiation (HR 0.32, p = 0.034 and HR 0.38, p = 0.018, respectively). Significant factors for DC were use of TT (HR 0.54, p = 0.022) and single BM (HR 0.47, p = 0.004). Reduced incidence of LMM was associated with use of TT (HR 0.42, p = 0.038), synchronicity (HR 0.25, p = 0.028), and controlled primary cancer (HR 0.44, p = 0.047). TT was associated with prolonged OS, improved DC, and reduced LMM in resected BM patients. WBRT and LBRT/SRS showed similar benefits on LC. Considering the extended survival of cancer patients and the long-term effect of WBRT on cognitive function, LBRT/SRS appears to be a good option after resection of BM.

Survival and prognostic factors in patients undergoing the resection of solitary brain metastasis from non-small cell lung cancer: a retrospective cohort study

“…However, in the subgroup of patients who received either targeted therapy or chemotherapy, we found that WBRT did not demonstrate survival benefits, which is consistent with the result of a meta-analysis that found no OS benefit with the addition of targeted therapy to radiotherapy ( 31 ). However, despite previous studies demonstrating that the KPS score is associated with survival outcomes ( 27 , 32 ), we did not observe this in the present study, which might attributable to the high overall KPS scores of our patients. Combining the beneficial features of high KPS, controlled primary disease, and single BM, it is not surprising that the median OS in this patient cohort was 27.1 months, which was longer than that reported previously (11.6–21.1 months) ( 10 , 22 , 27 ).…”

“…However, despite previous studies demonstrating that the KPS score is associated with survival outcomes ( 27 , 32 ), we did not observe this in the present study, which might attributable to the high overall KPS scores of our patients. Combining the beneficial features of high KPS, controlled primary disease, and single BM, it is not surprising that the median OS in this patient cohort was 27.1 months, which was longer than that reported previously (11.6–21.1 months) ( 10 , 22 , 27 ).…”

“…With the development of hippocampus-avoiding and other techniques, WBRT will likely still be widely used as a standard of care, before SRS/ SRT could, if possible, replace WBRT. Another retrospective study including patients who underwent resection of BM from different original malignancies demonstrated that the significant factors associated with improved OS included a higher KPS score, use of targeted treatment, controlled primary disease, and single BM (27). NSCLC with oncogenic driver mutations, such as EGFR or ALK, had a high predilection for BM compared to unselected patients (3,28).…”

Current status and perspectives of interventional clinical trials for brain metastases: analysis of ClinicalTrials.gov

“…At the same manner, immune checkpoint inhibitors (ICI) anti PD-1/PDL-1 (nivolumab, pembrolizumab, atezolizumab, durvalumab) and anti-CTLA-4 inhibitors (Ipilimumab, tremelimumab) are increasingly used for treating patients with advanced disease [12][13][14], whilst combining targeted-and immune-based therapies is being evaluated in a variety of solid tumors [15]. Notably, accordingly to the ability of these drug to penetrate the blood-brain barriers, targeted-and immune-based therapies, alone or in combination, have shown a therapeutic e ciency in treating BM [5][6][7][8], whilst increasing evidence suggest their use in combination with radiotherapy (RT) [16][17][18][19][20].…”