Management Of Central Nervous System Metastases Research Articles

Outcomes of Operated Cases of Central Nervous System Metastases at a Tertiary Cancer Hospital – An Analysis

Abstract Background: Recent advances in the treatment have increased the survival of patients with common cancers. As a result, the incidence of symptomatic central nervous system (CNS) metastases has increased over time. Although systemic therapies remain the mainstay of metastatic cancers, surgical treatment is often required for progressive neurological deficits and to buy time for other modalities to be effective. The present retrospective study aimed to analyze various demographic, neurological, and short-term survival outcomes among operated cases of symptomatic CNS metastases. Materials and Methods: All surgically treated symptomatic brain and spine metastasis patients between August 2018 and March 2022 were included in the study. Patients who underwent procedures for primary tumors of the brain and spine were excluded. The details of demographic and clinical profile, neurological data, surgical treatment, and short-term survival data were retrieved from hospital medical records and analyzed. Patients with motor deficits (power grade 3/5 or less) were analyzed to look for improvement in motor deficits after surgery. Results: The first 100 operated cases of symptomatic CNS metastases were reviewed. The mean age of presentation was 46.42 years (females – 44.28, males – 49.13). Breast malignancy was the most common source of primary overall (29%) and lung malignancy (15%) was second most common. A total of 53 brain surgeries and 47 spine surgeries were performed. Preoperative motor deficits were seen more commonly among spine metastases (30/47) than brain metastases (17/53) patients. Around 64% of patients who presented with neurological deficits (motor deficits) had improvement postsurgery. Such improvement from deficits was observed more in patients with spine metastases (23/30; 76.7%) than brain metastases (7/17; 41.2%). Conclusion: Neurosurgery has an important role in the management of CNS metastases, and timely surgical intervention in a selected group of symptomatic CNS metastases can improve the quality of life of the patients.

Management of CNS metastases in patients with EGFR mutation-positive NSCLC.

Central nervous system (CNS) metastases are a frequent and severe complication associated with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). The first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) have shown considerable efficacy in EGFR-mutated NSCLC. However, their limited potential to cross the blood-brain barrier (BBB) renders them less effective in the management of CNS metastases in NSCLC. Osimertinib, a third-generation irreversible EGFR-TKI with good potential to cross the BBB, has shown significant clinical activity and acceptable safety profile in patients with EGFR-positive NSCLC brain and leptomeningeal metastases. The progression-free survival (PFS) of up to 15.2 months in CNS metastases patients in the FLAURA trial and the CNS objective response rates (ORRs) of 54% and 43% in the AURA/AURA2 and BLOOM trials, respectively, have established the role of osimertinib in patients with NSCLC with CNS metastases. The AURA3 trial also reported a PFS of 8.5 months and overall ORR of 71%. These data have supported osimertinib to be recognized as a "preferred" first-line treatment for EGFR-positive metastatic NSCLC by the National Comprehensive Cancer Network (NCCN). With limited treatment options available, upfront administration of osimertinib in patients with NSCLC irrespective of EGFR T790M and CNS metastases may improve the overall response rate and potentially reduce the adverse effects of radiotherapy. Our review focuses on the management of EGFR-mutated NSCLC CNS metastases in the context of recent NCCN guidelines.

Systemic Therapy of Lung Cancer CNS Metastases Using Molecularly Targeted Agents and Immune Checkpoint Inhibitors.

Central nervous system (CNS) metastases most commonly arise from lung cancer, with the majority of patients affected during their disease course. The prognosis for patients with untreated brain metastases is poor, with surgical resection and/or radiotherapy as classic therapeutic options. However, the value of systemic therapy in the management of CNS metastases from lung cancer is growing. Novel targeted agents for the treatment of non-small cell lung cancer (NSCLC) have demonstrated activity in treating patients with CNS involvement, and are potential alternatives to radiation and surgery. These agents include anaplastic lymphoma kinase (ALK) inhibitors such as alectinib, crizotinib, ceritinib, lorlatinib, and others; epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, including the recently developed third-generation inhibitor osimertinib, and even immune checkpoint inhibitors such as nivolumab, pembrolizumab, and atezolizumab. This review summarizes current activity of systemic agents in the management of CNS metastases from NSCLC, as well as potential mechanisms of action of these small and large molecules.

Achievements and future developments of ALK-TKIs in the management of CNS metastases from ALK-positive NSCLC

Non-small cell lung cancer (NSCLC) represents the paradigm of personalized treatment of human cancer. Several oncogenic druggable alterations have been so far identified, with anaplastic lymphoma kinase (ALK) gene rearrangements being one of the newest and most appealing. Presence of ALK fusions is associated with some particular clinical and pathological features, including a preferential seeding into the central nervous system (CNS). In addition, ALK rearrangements are recognized as the strongest predictor for benefit of anti-ALK therapy. Crizotinib, the first ALK inhibitor (ALK-I) licensed in clinical practice, is the standard of care for newly diagnosed patients. Unfortunately, within the first year of treatment the majority of patients become insensitive to crizotinib, with approximately one third of them developing brain metastases (BMs). Optimal management of BMs is one of the major challenges in treating ALK positive NSCLC. Several novel and highly CNS penetrant ALK-Is are currently under investigation and available data clearly indicated their ability in controlling intracranial disease.

Abstract P6-11-12: CNS metastases in breast cancer: A comparison report

Abstract Background: Breast cancer is one of the most common causes of central nervous system (CNS) metastases, with 25-34% of patients experiencing brain metastases. Typically, CNS metastasis is associated with a dismal survival largely due to the inability of chemotherapeutic and biologic agents to cross the blood-brain barrier. In the last 5 to 7 years the management of CNS metastases utilizing targeted therapies, stereotactic radiation, and craniotomy have all shown to improve survival. We reviewed and analyzed data for CNS metastastic breast cancer treated at City of Hope (COH), a tertiary cancer center in California, in two cohorts between 2000-2005 and 2006-2011 to compare their survival. Methods/Results: A retrospective, comparative, correlational chart review was performed. Data from 172 women diagnosed with CNS metastases between 2000 and 2011 at COH, was evaluated. There were 47 patients in 2000-2005 and 125 patients in 2006-2011. The sample consisted of Caucasians (49.7%), Hispanics (26.1%), Asians (16.8%), and African Americans (7.4%). The median age at CNS diagnosis was 53 years old (24-87). Of these patients 38.2% were Her2neu positive, 30.6% ER/PR positive, and 21.4% triple negative (TN). In this cohort, the median survival for all patients with brain metastases is 5 months (0.03-85.6 months). The survival with brain metastasis among Her2neu positive, TN, and ER/PR positive is significantly different (8 months, 2.5 months, and, 5.3 months, respectively, p<0.0295). Limited sample size prevented the relatively substantial difference in patients with with Her2+ versus Her2- from reaching significance (median survival 8months vs 3.8 months respectively, p<0.0939). The median survival for patients diagnosed and treated in 2006-2011 is statistically significantly worse than those in 2000-20005 (4.4 months and 7 months, respectively, p = 0.0042). Most patients received treatment for brain metastases with one or more therapies, including whole brain radiation, stereotactic radiation, craniotomy, and intrathecal chemotherapy. Most of the patients who received chemotherapy, craniotomy, and/or stereotactic radiation were in the 2006-2011 group (100%, 82.5%, and 72.6%, respectively).There was also a shift in the incidence of patients with TN, her2neu positive, and ER/PR positive disease in the 2006-2011 as compared to 2000-2005 (24% vs 14.6%, p<0.004; 40% vs 31.3%, p<0.000; 31.2% vs 29.2%, p 0.033, respectively). Conclusion: The results of our study showed that despite the new therapies there was no change in survival for brain metastasis in breast cancer. In this single institution report, this may be in part due to an increase number of patients with TN and Her2neu positive CNS disease, better data collection, or due to better systemic control. We also noted an increase in the number of patients with brain metastases, which may be attributed to the increase in the number of patients presenting with metastatic breast cancer at COH for consideration of investigational therapies. Further studies aimed to determine why there is a shift in the tumor biology, as well as, to characterize risk factors for development of CNS disease and to develop new treatment strategies are warranted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-12.

Abstract ES1-1: Advances in the Neurosurgical Management of CNS Metastases

Abstract As the overall survival of patients with metastatic breast cancer improves, greater attention has been drawn to involvement specific to the central nervous system (CNS). Brain metastases are the most common intracranial tumor in adults with breast cancer representing the second most common type of CNS brain metastasis. These lesions are thought to develop in up to 20% of breast cancer patients with over 15,000 new cases predicted in the United States each year. Spinal metastases, some with involvement of the spinal cord, are also a frequent occurrence in the breast cancer patient with up to 30% of patients developing this form of the disease. Unfortunately, new systemic therapies for CNS metastases have had little impact on disease control, a critical factor in the improvement of quality of life and survival for this group of patients. Data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database reveal that one third of intra-cranial and one-half of spinal breast cancer patients with neurosurgically treated CNS metastases are alive at 1 year and that the overall post-operative survival has increased over time for spinal fusion procedures. We propose to review the current state of knowledge, the existing barriers to more successful neurosurgical treatment, and the future goals for treating CNS metastases with neurosurgical intervention. We will 1) review the clinical factors associated with the development of CNS metastases, 2) summarize current neurosurgical treatment strategies with evidence-based outcome data, 3) highlight possible directions for future research efforts. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES1-1.

Management of CNS metastases in small cell lung cancer: a consensus report

Introduction Prevention and treatment of central nervous system (CNS) metastases remain a major problem in the treatment of small cell lung cancer (SCLC). CNS metastases are normally categorized into parenchymal (brain) metastases, leptomeningeal carcinomatosis and spinal cord compression. The incidence rises with the length of survival [l-3]. The methodological difficulties in establishing the true dimensions of the problem and in evaluating treatment results have been addressed recently elsewhere [4,5]. The present report summarizes information obtained since the last IASLC workshop consensus report [6]. It includes points of interest for future work along with guidelines, in so far as current knowledge permits recommendations to be made. In-depth analysis of the role of elective cranial irradiation (PO, chemoand radiotherapy of CNS metastases and sequelae of these treatments has been prepared in conjunction with the present workshop and can be found elsewhere in this issue [7-91.