Society for Neuro-Oncology 2014 annual meeting updates on central nervous system metastases

Abstract Introduction The 19th Annual Meeting of the Society for Neuro-Oncology (SNO) took place in November of 2014. The focus of many abstracts, as well as the Education Day, was on recent advances in the study of central nervous system (CNS) metastases. Tumor Biology Key studies evaluating the factors in tumors and their microenvironment associated with the development and growth of brain metastases are reviewed. Prognostication Studies investigating the factors that independently influence survival in participants with brain metastases are presented. Response Assessment The Response Assessment for Neuro-Oncology criteria for brain metastases (RANO-BM) and the Neurological Assessment in Neuro-Oncology (NANO) criteria, which were both presented, are recapped. Radiotherapy Studies are reviewed evaluating factors that influence survival outcomes in participants with brain metastases who were treated with radiotherapy. Studies investigating the potential risk of radiation necrosis with the combination of radiotherapy and immunotherapies are presented. Systemic Therapies Brain metastases-focused subset analyses from the ASCEND-1 trial for ALK-translocated non–small cell lung cancer are presented. Preclinical and clinical work on solid tumor leptomeningeal carcinomatosis is also covered. Sequelae of Central Nervous System Metastases and Their Treatments An overview is provided of treatment- related toxicities as well as important concepts that may influence strategies to protect against these toxicities. Conclusions Key concepts regarding tumor biology, prognostication, response assessment, therapeutic management, and sequelae of treatment for CNS metastases are summarized. Advances in our understanding of the basic and clinical science of CNS metastases have the potential to improve outcomes for patients.

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Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Central Nervous System Metastases

Journal of Clinical Oncology ◽

10.1200/jco.2008.19.8481 ◽

2009 ◽

Vol 27 (31) ◽

pp. 5278-5286 ◽

Cited By ~ 151

Author(s):

Brian Leyland-Jones

Keyword(s):

Breast Cancer ◽

Central Nervous System ◽

Nervous System ◽

Epidermal Growth Factor Receptor ◽

Growth Factor Receptor ◽

Cns Metastases ◽

Her2 Positive ◽

Central Nervous System Metastases ◽

Epidermal Growth ◽

Positive Breast Cancer

PurposeTo determine the incidence, outcomes, and current strategies for management of brain metastases in patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer.MethodsA literature review was performed to obtain data on central nervous system metastases in patients with breast cancer.ResultsHER2 amplification/overexpression is a prognostic and predictive factor for the development of CNS metastases. Autopsy data show that the incidence rate for CNS metastases in patients with breast cancer is approximately 30%; this may be higher (ie, 30% to 50%) in patients with HER2-positive disease. Treatment with trastuzumab is not associated with an increased incidence of CNS metastases. Data from three phase III adjuvant trials showed the incidence was similar between patients who received trastuzumab and those who did not. Furthermore, trastuzumab can significantly improve overall survival in HER2-positive patients who already have CNS metastases compared with patients who do not receive trastuzumab or those who have HER2-negative brain metastases. This survival advantage is conferred via systemic control of the disease. The current standard of care for patients with CNS metastases is whole-brain radiotherapy (WBRT), with or without surgery, or stereotactic radiosurgery. In the future, novel therapies or combinations of therapies may additionally improve survival in these patients.ConclusionThe incidence of CNS metastases in trastuzumab-treated patients is similar to that in all patients with HER2-positive disease. Trastuzumab can improve survival in patients with HER2-positive disease with CNS metastases.

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Local and systemic treatment for HER2-positive breast cancer with brain metastases: a comprehensive review

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920953729 ◽

2020 ◽

Vol 12 ◽

pp. 175883592095372

Author(s):

Wing-Lok Chan ◽

Tai-Chung Lam ◽

Ka-On Lam ◽

Mai-Yee Luk ◽

Roger Ngan Kai-Cheong ◽

...

Keyword(s):

Breast Cancer ◽

Central Nervous System ◽

Nervous System ◽

Brain Metastases ◽

Special Focus ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Systemic Treatments ◽

Central Nervous System Metastases ◽

Positive Breast Cancer

The management of human epidermal growth factor receptor (HER2)-positive breast cancer has improved over the past decade. However, despite improvements in systemic control, a substantial proportion of patients with advanced HER2-positive breast cancer suffer from central nervous system metastases and even intracranial progression after aggressive local treatment. There is paucity of data and no consensus on the systemic therapies for patients with intracranial progression. This review discusses both local and systemic treatments for HER2-positive breast cancer with brain metastases with a special focus on the response of central nervous system metastases. A recommended practical treatment algorithm to guide physicians in selecting the most appropriate anti-HER2 therapy for their patients is suggested.

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Consensus Recommendations for MRI and PET Imaging of Primary Central Nervous System Lymphoma: Guideline Statement from the International Primary CNS Lymphoma Collaborative Group (IPCG)

Neuro-Oncology ◽

10.1093/neuonc/noab020 ◽

2021 ◽

Cited By ~ 1

Author(s):

Ramon F Barajas Jr ◽

Letterio S Politi ◽

Nicoletta Anzalone ◽

Heiko Schöder ◽

Christopher P Fox ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Tumor Imaging ◽

Primary Cns Lymphoma ◽

Central Nervous System Lymphoma ◽

Response Assessment ◽

Integrated Approach ◽

Collaborative Group ◽

Cns Lymphoma ◽

Consensus Recommendations

Abstract Advanced molecular and pathophysiologic characterization of Primary Central Nervous System Lymphoma (PCNSL) has revealed insights into promising targeted therapeutic approaches. Medical imaging plays a fundamental role in PCNSL diagnosis, staging, and response assessment. Institutional imaging variation and inconsistent clinical trial reporting diminishes the reliability and reproducibility of clinical response assessment. In this context, we aimed to: 1) critically review the use of advanced PET and MRI in the setting of PCNSL; 2) provide results from an international survey of clinical sites describing the current practices for routine and advanced imaging, and 3) provide biologically based recommendations from the International PCNSL Collaborative Group (IPCG) on adaptation of standardized imaging practices. The IPCG provides PET and MRI consensus recommendations built upon previous recommendations for standardized brain tumor imaging protocols (BTIP) in primary and metastatic disease. A biologically integrated approach is provided to addresses the unique challenges associated with the imaging assessment of PCNSL. Detailed imaging parameters facilitate the adoption of these recommendations by researchers and clinicians. To enhance clinical feasibility, we have developed both “ideal” and “minimum standard” protocols at 3T and 1.5T MR systems that will facilitate widespread adoption.

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Osimertinib versus afatinib in patients with T790M-positive, non-small-cell lung cancer and multiple central nervous system metastases after failure of initial EGFR-TKI treatment

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01539-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yang Yang ◽

Qilong Liu ◽

Lei Cao ◽

Wei Sun ◽

Xiaowei Gu ◽

...

Keyword(s):

Lung Cancer ◽

Central Nervous System ◽

Nervous System ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Cns Metastases ◽

Tki Treatment ◽

Egfr Tki

Abstract Background The purpose of this study was to compare the efficacy of osimertinib (OSI) versus afatinib (AFA) in patients with T790M-positive, non-small-cell lung cancer (NSCLC) and multiple central nervous system (CNS) metastases after failure of initial epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. Methods Consecutive patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment were retrospectively identified from our medical institution during 2016–2018 and underwent either oral 80 daily OSI or oral 40 daily AFA every 3 weeks for up to 6 cycles, until disease progression, intolerable adverse events (AEs), or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS). Results The cohort consisted of 124 patients (OSI: n = 60, mean age = 64.24 years [SD: 12.33]; AFA: n = 64, mean age = 64.13 years [SD: 13.72]). After a median follow-up of 24 months (range, 3 to 28), a significant improvement in OS was detected (hazard ratio [HR] 0.59, 95% confidence interval [CI], 0.39–0.91; p = 0.0160; median, 13.7 months [95% CI, 11.1–14.8] for OSI vs 9.6 months [95% CI, 8.4–10.2] for AFA). The median duration of PFS was significantly longer with OSI than with AFA (HR 0.62; 95% CI, 0.41–0.91; p = 0.014; median, 4.5 months [95% CI, 3.5–5.7] vs 3.9 months [95% CI, 3.1–4.8]). The proportion of grade 3 or higher adverse events (AEs) was lower with OSI (22.4%) than with AFA (39.4%). Conclusions In patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment, OSI may be associated with significantly improved survival benefit compared with AFA, with a controllable tolerability profile.

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Oral Targeted Therapies and Central Nervous System (CNS) Metastases

CNS Drugs ◽

10.1007/s40263-015-0283-6 ◽

2015 ◽

Vol 29 (11) ◽

pp. 935-952 ◽

Cited By ~ 2

Author(s):

Michael P. Gabay ◽

Scott M. Wirth ◽

Joan M. Stachnik ◽

Colleen L. Overley ◽

Katie E. Long ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Targeted Therapies ◽

Cns Metastases

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Central Nervous System Metastases from Primary Epithelial Ovarian Cancer

Cancer Control ◽

10.1177/107327480301000309 ◽

2003 ◽

Vol 10 (3) ◽

pp. 244-253 ◽

Cited By ~ 18

Author(s):

Lalit Kumar ◽

Suchitra Barge ◽

Ashok K. Mahapatra ◽

Sanjay Thulkar ◽

Gaura Kishore Rath ◽

...

Keyword(s):

Ovarian Cancer ◽

Central Nervous System ◽

Nervous System ◽

Epithelial Ovarian Cancer ◽

Central Nervous System Metastases ◽

Primary Epithelial Ovarian Cancer

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Central nervous system metastases in malignant melanoma

Neurosurgery ◽

10.1097/00006123-198101000-00006 ◽

1981 ◽

Vol 8 (1) ◽

pp. 26???30 ◽

Cited By ~ 1

Author(s):

D E Bullard ◽

E B Cox ◽

H F Seigler

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Malignant Melanoma ◽

Central Nervous System Metastases

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The influence of brain metastases on the central nervous system effects of methylnaltrexone: a post hoc analysis of 3 randomized, double-blind studies

Supportive Care in Cancer ◽

10.1007/s00520-021-06070-7 ◽

2021 ◽

Author(s):

Darren M. Brenner ◽

Neal E. Slatkin ◽

Nancy Stambler ◽

Robert J. Israel ◽

Paul H. Coluzzi

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Brain Metastases ◽

Cancer Patients ◽

Opioid Withdrawal ◽

Double Blind ◽

Post Hoc Analysis ◽

Pain Scores ◽

Opioid Receptor Antagonists ◽

Post Hoc

Abstract Purpose Peripherally acting μ-opioid receptor antagonists such as methylnaltrexone (MNTX, Relistor®) are indicated for the treatment of opioid-induced constipation (OIC). The structural properties unique to MNTX restrict it from traversing the blood-brain barrier (BBB); however, the BBB may become more permeable in patients with brain metastases. We investigated whether the presence of brain metastases in cancer patients compromises the central effects of opioids among patients receiving MNTX for OIC. Methods This post hoc analysis of pooled data from 3 randomized, placebo-controlled trials included cancer patients with OIC who received MNTX or placebo. Endpoints included changes from baseline in pain scores, rescue-free laxation (RFL) within 4 or 24 h of the first dose, and treatment-emergent adverse events (TEAEs), including those potentially related to opioid withdrawal symptoms. Results Among 356 cancer patients in the pooled population, 47 (MNTX n = 27; placebo n = 20) had brain metastases and 309 (MNTX n = 172; placebo n = 137) did not have brain metastases. No significant differences in current pain, worst pain, or change in pain scores from baseline were observed between patients treated with MNTX or placebo. Among patients with brain metastases, a significantly greater proportion of patients who received MNTX versus placebo achieved an RFL within 4 h after the first dose (70.4% vs 15.0%, respectively, p = 0.0002). TEAEs were similar between treatment groups and were generally gastrointestinal in nature and not related to opioid withdrawal. Conclusion Focal disruptions of the BBB caused by brain metastases did not appear to alter central nervous system penetrance of MNTX.

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