Local Control of Brain Metastasis: Treatment Outcome of Focal Brain Treatments in Relation to Subtypes

정재욱,안성귀,이학민,박종태,이승아,박세호,정준,김승일 한국유방암학회 2015 Journal of breast cancer Vol.18 No.1

Purpose: To investigate treatment options for local control of metastasisin the brain, we compared focal brain treatment (FBT)with or without whole brain radiotherapy (WBRT) vs. WBRT alone,for breast cancer patients with tumor relapse in the brain. We alsoevaluated treatment outcomes according to the subtypes. Methods:We conducted a retrospective review of breast cancer patientswith brain metastasis after primary surgery. All patients receivedat least one local treatment for brain metastasis. Surgeryor stereotactic radiosurgery was categorized as FBT. Patientswere divided into two groups: the FBT group received FBT±WBRT, whereas the non-FBT group received WBRT alone. Subtypeswere defined as follows: hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HRpositive/HER2-positive, HR-negative/HER2-positive, and triplenegative(TN). We examined the overall survival after brain metastasis(OSBM), brain metastasis-specific survival (BMSS), andbrain metastasis-specific progression-free survival (BMPFS). Results:A total of 116 patients were identified. After a median follow-up of 50.9 months, the median OSBM was 11.5 months(95% confidence interval, 9.0–14.1 months). The FBT groupshowed significantly superior OSBM and BMSS. However, FBTwas not an independent prognostic factor for OSBM and BMSSon multivariate analyses. In contrast, multivariate analysesshowed that patients who underwent surgery had improvedBMPFS, indicating local control of metastasis in the brain. FBTresulted in better BMPFS in patients with HR-negative/HER2-positive cancer or the TN subtype. Conclusion: We found that patientswho underwent surgery experienced improved local controlof brain metastasis, regardless of its extent. Furthermore, FBTshowed positive results and could be considered for better localcontrol of brain metastasis in patients with aggressive subtypessuch as HER2-positive and TN.

Case Series of Soft Tissue Sarcoma Patients with Brain Metastasis with Implications from Genomic and Transcriptomic Analysis

박창희,김록현,최재용,김미소,김태민,한일규,김종일,김한수 대한암학회 2024 Cancer Research and Treatment Vol.56 No.2

Purpose Brain metastasis rarely occurs in soft tissue sarcoma (STS). Here, we present five cases of STS with brain metastases with genetic profiles.Materials and Methods We included five patients from Seoul National University Hospital who were diagnosed with STS with metastasis to the brain. Tissue from the brain metastasis along with that from the primary site or other metastases were used for DNA and RNA sequencing to identify genetic profiles. Gene expression profiles were compared with sarcoma samples from The Cancer Genome Atlas.Results The overall survival after diagnosis of brain metastasis ranged from 2.2 to 34.3 months. Comparison of mutational profiles between brain metastases and matched primary or other metastatic samples showed similar profiles. In two patients, copy number variation profiles between brain metastasis and other tumors showed several differences including <i>MYCL, JUN, MYC</i>, and <i>DDR2</i> amplification. Gene ontology analysis showed that the group of genes significantly highly expressed in the brain metastasis samples was enriched in the G-protein coupled receptor activity, structural constituent of chromatin, protein heterodimerization activity, and binding of DNA, RNA, and protein. Gene set enrichment analysis showed enrichment in the pathway of neuroactive ligand-receptor interaction and systemic lupus erythematosus.Conclusion The five patients had variable ranges of clinical courses and outcomes. Genomic and transcriptomic analysis of STS with brain metastasis implicates possible involvement of complex expression modification and epigenetic changes rather than the addition of single driver gene alteration.

Genomic and Molecular Characterization of Brain Tumors in Asian and Non-Asian Patients of Los Angeles: A Single Institution Analysis

( Courtney Duong ),( Thien Nguyen ),( John P. Sheppard ),( Vera Ong ),( Lawrance K. Chung ),( Daniel T. Nagasawa ),( Isaac Yang ) 대한뇌종양학회·대한신경종양학회·대한소아뇌종양학회 2017 Brain Tumor Research and Treatment Vol.5 No.2

Background Worldwide, approximately 2% of new cancers are of the brain. Five-year survival rates among brain cancer patients have been reported as a little over a third. Differences in clinical outcomes between brain tumor patients of different races remain poorly understood. Methods A retrospective chart review was performed on brain tumor resection patients≥18 years old. Demographics, treatment variables, and survival outcomes were collected. Primary outcomes were length of stay, recurrence rate, progression-free survival (PFS), and overall survival (OS). Results A total of 452 patients were included in analysis. Females and males had nearly a 1:1 ratio (n=242 and n=220, respectively). Mean age was 54.8 years (SD: 14.5 range: 18-90). Females composed 69% (n=48) of Asian patients; males constituted 31% (n=22). Mean age of the Asian pa-tients was 55.9 years (SD: 14.6 range: 26-89). Asian-only cohort tumor pathologies included glioblas-toma (GBM) (n=14), high-grade glioma (n=7), low-grade glioma (n=4), meningioma (n=38), and metastases (n=7). Of the 185 meningioma patients, non-Asian patients comprised 79% of the group (n=146). Of the 65 GBM patients in total, non-Asian patients made up 89% of the GBM cohort (n=58). There were no statistically significant differences between these groups of both cohorts in recurrence (p= 0.1580 and p=0.6294, respectively), PFS (p=0.9662 and p=0.4048, respectively), or OS (p=0.3711 and p=0.8183, respectively). Conclusion Studies evaluating the survival between patients of different racial backgrounds against several tumor varieties are rare. Patients of certain racial backgrounds may need additional consider-ation when being attended to despite the same mutational composition as their counterparts. Repeated studies using national databases may yield more conclusive results.

CASE REPORT : Thrombosed Large Middle Cerebral Artery Aneurysm Mimicking an Intra-Axial Brain Tumor: Case Report and Review of Literature

( Young Joo Kim ),( Sin Soo Jeun ),( Jae Hyun Park ) 대한뇌종양학회 대한신경종양학회 2015 Brain Tumor Research and Treatment Vol.3 No.1

This case report presents a fully thrombosed large aneurysm of middle cerebral artery mimicking an intra-axial brain tumor in a 54-year-old male patient. A small mass like lesion was found incidentally in right frontal area. Brain magnetic resonance image showed dark signal intensity on T2-weighted images and peripheral high signal intensity on T1-weighted images with peripheral rim enhancement. We considered intra-axial tumors such as glioma or metastatic tumor as a differential diagnosis. The lesion was approached transcortically, and intraoperatively, the lesion was found to be a large thrombosed aneurysm originating from the lateral lenticulostriate artery of right middle cerebral artery. One vascular clip was applied at the parent artery, and the thrombosed aneurysm was totally removed. There have been many reports of other intracranial lesions wrongly diagnosed as intracranial neoplasms. And thrombosed aneurysms mimicking intracranial neoplasm have been reported in 4 cases previously. According to those case reports, there were no efficient imaging tools to differentiate between these thrombosed aneurysms and intracranial neoplasms. We reviewed those reports and considered about the efficient method to diagnosed accurately before surgery. To sum up, when a patient presents with an intracranial lesion lying on the course of major or distal cerebral arteries, the surgeon should have thrombosed aneurysm in mind as one of the differential diagnosis and be prepared when surgically treating such lesions.

The Pattern of Care for Brain Metastasis from Breast Cancer over the Past 10 Years in Korea: A Multicenter Retrospective Study (KROG 16-12)

김재식,김규보,정원근,신경환,임석아,김희준,김용배,장지석,김지현,최두호,박연희,김대용,김태현,최병옥,이시원,김수지,권진이,강기문,정웅기,김경수,남지호,윤원섭,김진희,차지혜,오윤경,김인아 대한암학회 2022 Cancer Research and Treatment Vol.54 No.4

Purpose We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. Materials and Methods We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). Results Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. Conclusion The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years. Purpose We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea.Materials and Methods We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients).Results Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance.Conclusion The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

Case Reports : Paroxysmal Autonomic Dysregulation with Fever that was Controlled by Propranolol in a Brain Neoplasm Patient

Su Jin Oh,Yun Kyung Hong,Eun Kee Song 대한내과학회 2007 The Korean Journal of Internal Medicine Vol.22 No.1

Intractable fever in cancer patients is problematic and the causes of this fever can be diverse. Paroxysmal persistent hyperthermia after sudden mental change or neurologic deficit can develop via autonomic dysregulation without infection or any other causes of fever. Paroxysmal hyperthermic autonomic dysregulation is a rare disease entity. It manifests as a form of paroxysmal hypertension, fever, tachycardia, tachypnea, pupillary dilation, agitation and extensor posturing after traumatic brain injury, hydrocephalus, brain hemorrhage or brain neoplasm. We recently experienced a case of paroxysmal hyperthermia following intracerebral hemorrhage along with brain neoplasm. Extensive fever workups failed to show an infectious or inflammatory source and/or hormonal abnormality. Empirical treatments with antibiotics, antipyretics, morphine, steroid and antiepileptic agents were also ineffective. However, Propranolol, a lipophilic beta-blocker, successfully controlled the fever and stabilized the patient. Fever in cancer patients is a common phenomenon, but a central origin should be considered when the fever is intractable. Propranolol is one of the most effective drugs for treating paroxysmal hyperthermia that is due to autonomic dysregulation.

Co-expression of Survivin and Bcl-2 in Primary Brain Tumors : Their Potential Effect on Anti-apoptosis

Ryu, Je-Il,Kim, Choong-Hyun,Cheong, Jin-Hwan,Bak, Koang-Hum,Kim, Jae-Min,Oh, Suck-Jun The Korean Neurosurgical Society 2006 Journal of Korean neurosurgical society Vol.40 No.1

Objective : Survivin is an inhibitor of apoptosis protein[IAP], which inhibits apoptosis through a pathway distinct from the Bcl-2 family members. Overexpression of survivin and Bcl-2 have been commonly reported in human neoplasms. The authors investigate whether there is a synergistic effect on the anti-apoptosis rate of primary brain tumors "in situ" based on the co-expression of survivin and Bcl-2. Methods : One hundred and two brain tumor patients who had been resected were included in this study. Survivin tin and Bcl-2 were detected by Western blotting analysis, while apoptosis was examined by DNA fragmentation analysis. An anti-apoptotic rate was assessed in these brain tumor samples based on the expression of survivin and Bcl-2 or co-expression of both. Results : Survivin and Bcl-2 were expressed in 57[55.9%] and 53[52.0%] of 102 brain tumor samples studied respectively, and co-expressed in 31[30.4%]. The percentage of astrocytic and meningeal tumors expressing survivin was significantly correlated with histological grades; however, Bcl-2 was not correlated [p=0.106]. The anti-apoptotic rate in primary brain tumors with survivin, Bcl-2, and both was detected in 49[86.0%] of 57 samples, 42[79.9%] of 53 samples, and 27[87.1%] of 31 samples, respectively. Their difference in the frequency of anti-apoptosis was not significant. Conclusion : Survivin or Bcl-2 is involved in the anti-apoptosis. However, it suggests that co-expression of survivin and Bcl-2, together, have no synergistic effect on the anti-apoptotic properties of the primary brain tumors.

Understanding the Brain-Heart Connection Through a Case of Angry Glioma Syndrome

( Johanna Vaylen M. Sarmiento ),( Rhoderick M. Casis ),( Paul Vincent A. Opinaldo ) 대한뇌종양학회·대한신경종양학회·대한소아뇌종양학회 2024 Brain Tumor Research and Treatment Vol.12 No.2

We discuss a patient with a tumor on the anterior corpus callosum who underwent open biopsy eventually succumbing to cerebrogenic fatal arrhythmia following wounded glioma syndrome. A healthy 37-year-old female patient was admitted to our department due to a history of headache for 13 months. MRI revealed a suspicious glioma infiltrating the anterior corpus callosum. Neurologic examination only showed low cognitive assessment score (Montreal Cognitive Assessment score 20/30). ECG was normal sinus rhythm. Steroids and levetiracetam were administered prior to operation. Patient underwent right frontal craniotomy and biopsy of tumor with unremarkable events. During the first hospital day, patient had episodes of bradycardia followed by decrease in sensorium. Brain CT scan showed progression of edema without hemorrhage within the tumor bed. This was followed minutes later by two episodes of generalized tonic-clonic seizures and pulseless ventricular tachycardia. Cardiac resuscitation was done for 24 minutes but patient eventually expired. Location of the lesion and the epileptogenicity of the peritumoral cortex greatly contributed to the patient’s demise. Involvement of the frontomesial structures, particularly the insula and the cingulate cortex, and their connection to the central autonomic network, increased susceptibility to arrhythmias. Decreased seizure threshold worsened post-operative edema, further aggravating the dysregulation of the brain-heart-connection.

Stereotactic radiosurgery for brain metastasis in non-small cell lung cancer

Won, Yong Kyun,Lee, Ja Young,Kang, Young Nam,Jang, Ji Sun,Kang, Jin-Hyoung,Jung, So-Lyoung,Sung, Soo Yoon,Jo, In Young,Park, Hee Hyun,Lee, Dong-Soo,Chang, Ji Hyun,Lee, Yun Hee,Kim, Yeon-Sil The Korean Society for Radiation Oncology 2015 Radiation Oncology Journal Vol.33 No.3

Purpose: Stereotactic radiosurgery (SRS) has been introduced for small-sized single and oligo-metastases in the brain. The aim of this study is to assess treatment outcome, efficacy, and prognostic variables associated with survival and intracranial recurrence. Materials and Methods: This study retrospectively reviewed 123 targets in 64 patients with non-small cell lung cancer (NSCLC) treated with SRS between January 2006 and December 2012. Treatment responses were evaluated using magnetic resonance imaging. Overall survival (OS) and intracranial progression-free survival (IPFS) were determined. Results: The median follow-up was 13.9 months. The median OS and IPFS were 14.1 and 8.9 months, respectively. Fifty-seven patients died during the follow-up period. The 5-year local control rate was achieved in 85% of 108 evaluated targets. The 1- and 2-year OS rates were 55% and 28%, respectively. On univariate analysis, primary disease control (p < 0.001), the Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs. 2; p = 0.002), recursive partitioning analysis class (1 vs. 2; p = 0.001), and age (<65 vs. ${\geq}65$ years; p = 0.036) were significant predictive factors for OS. Primary disease control (p = 0.041) and ECOG status (p = 0.017) were the significant prognostic factors for IPFS. Four patients experienced radiation necrosis. Conclusion: SRS is a safe and effective local treatment for brain metastases in patients with NSCLC. Uncontrolled primary lung disease and ECOG status were significant predictors of OS and intracranial failure. SRS might be a tailored treatment option along with careful follow-up of the intracranial and primary lung disease status.

Stereotactic radiosurgery for brain metastasis in non-small cell lung cancer

Yong Kyun Won,Ja Young Lee,Young Nam Kang,Ji Sun Jang,Jin-Hyoung Kang,So-Lyoung Jung,Soo Yoon Sung,In Young Jo,Hee Hyun Park,Dong-Soo Lee,Ji Hyun Chang,Yun Hee Lee,Yeon-Sil Kim 대한방사선종양학회 2015 Radiation Oncology Journal Vol.33 No.3

Purpose: Stereotactic radiosurgery (SRS) has been introduced for small-sized single and oligo-metastases in the brain. The aim of this study is to assess treatment outcome, efficacy, and prognostic variables associated with survival and intracranial recurrence. Materials and Methods: This study retrospectively reviewed 123 targets in 64 patients with non-small cell lung cancer (NSCLC) treated with SRS between January 2006 and December 2012. Treatment responses were evaluated using magnetic resonance imaging. Overall survival (OS) and intracranial progression-free survival (IPFS) were determined. Results: The median follow-up was 13.9 months. The median OS and IPFS were 14.1 and 8.9 months, respectively. Fifty-seven patients died during the follow-up period. The 5-year local control rate was achieved in 85% of 108 evaluated targets. The 1- and 2-year OS rates were 55% and 28%, respectively. On univariate analysis, primary disease control (p < 0.001), the Eastern Cooperative Oncology Group (ECOG) performance status (0–1 vs. 2; p = 0.002), recursive partitioning analysis class (1 vs. 2; p = 0.001), and age (<65 vs. ≥65 years; p = 0.036) were significant predictive factors for OS. Primary disease control (p = 0.041) and ECOG status (p = 0.017) were the significant prognostic factors for IPFS. Four patients experienced radiation necrosis. Conclusion: SRS is a safe and effective local treatment for brain metastases in patients with NSCLC. Uncontrolled primary lung disease and ECOG status were significant predictors of OS and intracranial failure. SRS might be a tailored treatment option along with careful follow-up of the intracranial and primary lung disease status.