Leptomeningeal Metastasis in ER + HER2- Advanced Breast Cancer Patients: A Review of the Cases in a Single Institute Over a 15-year Period.

PURPOSE: While leptomeningeal metastasis (LM) from estrogen receptor-positive, HER2-negative advanced breast cancer (ER + HER2-ABC) has a poor prognosis, the details of ER + HER2-LM are unclear. We therefore retrospectively investigated patients with LM from ER + HER2-ABC. METHODS: ER + HER2-ABC patients who received any therapy at Shizuoka Cancer Center between October 2002 and December 2017 were retrospectively analyzed. Patients with central nervous system (CNS) metastases were divided into three groups: brain metastasis (BM) only (B group); BM with LM (BL group); and LM only (L group). RESULTS: Among 369 patients, 102 developed CNS metastases: 70 (68.6%), 13 (12.8%), and 19 (18.6%) in the B, BL, and L groups, respectively. The L group showed a later onset, poorer performance status, more symptoms, and more skull metastasis than the other groups. Radiotherapy as the initial treatment was introduced to 13/13 (100%) and 15/19 (78.9%) in the BL and L groups, respectively. Subsequent systemic therapy excluding best supportive care was introduced to 5/13 (38.5%) and 5/19 (26.3%) in the BL and L groups, respectively. The median overall survival from the diagnosis of CNS lesions was 295.0, 146.0, and 99.0 days in the B, BL, and L groups, respectively, and worsening of CNS lesions was the major cause of death in the BL and L groups. Multivariate analyses showed that concurrent soft tissue metastasis (hazard ratio, 4.620) and subsequent systemic therapy (hazard ratio, 0.063) were prognostic for the L group. CONCLUSION: Management of LM from ER + HER2-ABC remains challenging, so a multimodal approach with novel systemic therapy is warranted.

Prevalence of incidental meningiomas and gliomas on MRI: a meta-analysis and meta-regression analysis.

BACKGROUND: The chance of incidentally detecting brain tumors is increasing as the utilization of magnetic resonance imaging (MRI) becomes more prevalent. In this background, knowledge is accumulating in relation to the prediction of their clinical sequence. However, their prevalence-especially the prevalence of glioma-has not been adequately investigated according to age, sex, and region. METHOD: We systematically reviewed the articles according to the PRISMA statement and calculated the prevalence of meningiomas and diffuse gliomas in adults using a generalized linear mixed model. Specifically, the differences related to age, sex, and region were investigated. RESULTS: The pooled prevalence of incidental meningiomas in MRI studies was 0.52% (95% confidence interval (CI) [0.34-0.78]) in 37,697 individuals from 36 studies. A meta-regression analysis showed that the prevalence was significantly higher in elderly individuals, women, and individuals outside Asia; this remained statistically significant in the multivariate meta-regression analysis. The prevalence reached to 3% at 90 years of age. In contrast, the prevalence of gliomas in 30,918 individuals from 18 studies was 0.064% (95%CI [0.040 - 0.104]). The meta-regression analysis did not show a significant relationship between the prevalence and age, male sex, or region. The prevalence of histologically confirmed glioma was 0.026% (95%CI [0.013-0.052]). CONCLUSIONS: Most of meningiomas, especially those in elderlies, remained asymptomatic, and their prevalence increased with age. However, the prevalence of incidental gliomas was much lower and did not increase with age. The number of gliomas that developed and the number that reached a symptomatic stage appeared to be balanced.

Retrospective analysis of salvage surgery for local progression of brain metastasis previously treated with stereotactic irradiation: diagnostic contribution, functional outcome, and prognostic factors.

BACKGROUND: Stereotactic irradiation (STI) is a primary treatment for patients with newly diagnosed brain metastases. Some of these patients experience local progression, which is difficult to differentiate from radiation necrosis, and difficult to treat. So far, just a few studies have clarified the prognosis and effectiveness of salvage surgery after STI. We evaluated the diagnostic value and improvement of functional outcomes after salvage surgery. Based on these results, we reconsidered surgical indication for patients with local progression after STI. METHODS: We evaluated patients with brain metastases treated with salvage surgery for local progression from October 2002 to July 2019. These patients had undergone salvage surgery based on magnetic resonance imaging findings and/or clinical evidence of post-STI local progression and stable systemic disease. We employed two prospective strategies according to the eloquency of the lesions. Lesions in non-eloquent areas had been resected completely with a safety margin, utilizing a fence-post method; while lesions in eloquent areas had been treated with minimal resection and postoperative STI. Kaplan-Meier curves were used for the assessment of overall survival. Prognostic factors for survival were analyzed. RESULTS: Fifty-four salvage surgeries had been performed on 48 patients. The median age of patients was 63.5 years (range 36-79). The median interval from STI to surgery was 12 months. The median overall survival was 20.2 months from salvage surgery and 37.5 months from initial STI. Primary cancers were lung 31, breast 9, and others 8. Local recurrence developed in 13 of 54 lesions (24%). Leptomeningeal dissemination occurred after surgery in 3 patients (5.6%). Primary breast cancer (breast vs. lung: HR: 0.17), (breast vs. others: HR: 0.08) and RPA class 1-2 (RPA 1 vs. 3, HR:0.13), (RPA 2 vs 3, HR:0.4) were identified as good prognostic factors for overall survival (OS) in multivariate analyses. The peripheral neutrophil-to-lymphocyte ratio (NLR) of ≤3.65 predicted significantly longer OS (median 25.5 months) than an NLR > 3.65 (median 8 months). CONCLUSION: We insist that salvage surgery leads to rapid improvement of neurological function and clarity of histological diagnosis. Salvage surgery is recommended for large lesions especially with surrounding edema either in eloquent or non-eloquent areas.

Genetic analysis in patients with newly diagnosed glioblastomas treated with interferon-beta plus temozolomide in comparison with temozolomide alone.

PURPOSE: This study aimed to explore the genetic alterations and to identify good responders in the experimental arm in the tumor samples from newly diagnosed glioblastoma (GBM) patients enrolled in JCOG0911; a randomized phase II trial was conducted to compare the efficacy of interferonß (IFNß) plus temozolomide (TMZ) with that of TMZ alone. EXPERIMENTAL: DESIGN: Of 122 tumors, we performed deep targeted sequencing to determine the somatic mutations, copy number variations, and tumor mutation burden; pyrosequencing for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation; Sanger sequencing for the telomerase reverse transcriptase (TERT) promoter; and microsatellite instability (MSI) testing in 95, 91, 91 and 72 tumors, respectively. We performed a multivariable Cox regression analysis using backward stepwise selection of variables including clinical factors (sex, age, performance status, residual tumor after resection, tumor location) and genetic alterations. RESULTS: Deep sequencing detected an IDH1 mutation in 13 tumors (14%). The MGMT promoter methylation by quantitative pyrosequencing was observed in 41% of the tumors. A mutation in the TERT promoter was observed in 69% of the tumors. While high tumor mutation burden (> 10 mutations per megabase) was seen in four tumors, none of the tumors displayed MSI-high. The clinical and genetic factors considered as independent favorable prognostic factors were gross total resection (hazard ratio [HR]: 0.49, 95% confidence interval, 0.30-0.81, P = 0.0049) and MGMT promoter methylation (HR: 0.43, 0.21-0.88, P = 0.023). However, tumor location at the temporal lobe (HR: 1.90, 1.22-2.95, P = 0.0046) was an independent unfavorable prognostic factor. No predictive factors specific to the TMZ + IFNß + Radiotherapy (RT) group were found. CONCLUSION: This additional sub-analytical study of JCOG0911 among patients with newly diagnosed GBM showed that tumor location at the temporal lobe, gross total resection, and MGMT promoter methylation were significant prognostic factors, although no factors specific to IFNß addition were identified.

Surgical outcome and graded prognostic assessment of patients with brain metastasis from adult sarcoma: multi-institutional retrospective study in Japan.

BACKGROUND: Brain metastasis (BM) is an uncommon complication of sarcomas with a poor prognosis. Little information is available about the feasibility and prognostic factors of surgical resection of BM from sarcomas. METHODS: This study involved a retrospective analysis of 22 patients with BM from sarcomas who underwent resection at six institutes in Japan. Prognostic factors were analyzed to develop a graded prognostic assessment (GPA) using the log-rank test and Cox regression analysis. For validation of this GPA, we collected data on 100 surgical cases from 48 published reports. RESULTS: Postoperative Karnofsky Performance Status (KPS) improved in 50% of our patients. Median overall survival (OS) was 21 months. Multivariate analysis showed age and alveolar soft part sarcoma (ASPS) were significant preoperative prognostic factors (P < 0.05). RTOG-RPA classification had no significant prognostic value. We developed a GPA system for OS after resection of BM. A score of 0 was assigned to patients aged 18-29 years with non-ASPS, 2 to patients aged 18-29 years with ASPS or 30-76 years with non-ASPS, and 4 to patients aged 30-76 years with ASPS. Median OS for patients with GPA scores of 0, 2, and 4 were 6.5, 16.0, and 44.0 months, respectively (P = 0.002). The results were validated by the data of 100 cases compiled (P < 0.001). CONCLUSION: Median OS of patients with BM from sarcomas was comparable to that from carcinomas after resection. A new sarcoma-specific GPA may help patients and clinicians to select resection as an option for treatment of BM from sarcomas.

Posterior reversible encephalopathy syndrome (PRES) induced by pazopanib, a multi-targeting tyrosine kinase inhibitor, in a patient with soft-tissue sarcoma: case report and review of the literature.

Posterior reversible encephalopathy syndrome (PRES) is a clinical entity characterized by acute neurological symptoms such as severe headache, seizures, and visual disturbance, and by typical reversible lesion on brain magnetic resonance (MR) images. Since PRES is thought to be caused by vascular endothelial injury due to cytotoxic agents or acute systemic hypertension, the number of reports on PRES associated with angiogenesis inhibitors has been increasing. Although five cases that developed PRES due to pazopanib for renal cell carcinoma have already been reported, none of PRES due to pazopanib for soft-tissue sarcoma has been reported thus far. We describe a case of a 49-year-old woman with retroperitoneal soft-tissue sarcoma who developed PRES during pazopanib administration. Pazopanib at 800 mg/day was administered as her third-line treatment at relapse. After 38 days of pazopanib, she was admitted to our hospital with severe headache, vomiting, and systemic hypertension. The next day, she developed consciousness deterioration and visual disturbance together with exacerbated systemic hypertension. Brain MR images revealed hyper-intense signals on FLAIR sequences in the bilateral occipital lobes and the left thalamus. Intravenous nicardipine injection was immediately started to control her blood pressure and pazopanib was discontinued. Her symptoms gradually improved and disappeared on the fifth hospital day. After 2 weeks, hyper-intense signals on a FLAIR sequence disappeared completely. She restarted a low dose of pazopanib under good blood pressure control and experienced no subsequent recurrence of PRES.

JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonß plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma.

PURPOSE: This study explored the superiority of temozolomide (TMZ) + interferonß (IFNß) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. EXPERIMENTAL DESIGN: Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m2, daily) followed by TMZ maintenance (100-200 mg/m2/day, days 1-5, every 4 weeks) for 2 years. Patients in the TMZ + IFNß + RT arm intravenously received IFNß (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8). RESULTS: Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNß + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65-1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85-1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNß + RT (grade 3-4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%. CONCLUSIONS: TMZ + IFNß + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.

Clinical outcomes of brain metastases from hepatocellular carcinoma: a multicenter retrospective study and a literature review.

INTRODUCTION: The introduction of systemic chemotherapy for advanced hepatocellular carcinoma in recent years has led to the prediction that cases of brain metastases from hepatocellular carcinoma will increase. However, because brain metastases from hepatocellular carcinoma are relatively rare, the characteristics of this pathology are poorly understood. METHODS: We carried out a multicenter retrospective study to verify the characteristics of brain metastases from hepatocellular carcinoma in Japan. RESULTS: A total of 38 patients were enrolled and patient characteristics were poor general condition in many patients due to the progression of primary cancers. Stereotactic radiosurgery/stereotactic radiotherapy alone was the most common treatment (39.5%), with best supportive care provided for 10.5%. Median survival was 6 months, the neurological death rate was 28%, and the rate of brain hemorrhage was high (39.5%). Overall survival was analyzed for correlations with age, etiology of chronic liver disease, albumin-bilirubin (ALBI) grade, RPA classification, control of the primary tumor, number of brain metastases, brain hemorrhage, surgical resection, and radiotherapy. In multivariate analysis, ALBI grade, number of brain metastases and brain hemorrhage showed statistically significant correlation. CONCLUSIONS: A multivariate analysis extracted three items-ALBI grade, number of brain metastases, and brain hemorrhage-as prognostic factors for survival of brain metastases from hepatocellular carcinoma.

[Classification of Clinical Syndromes Associated with Skull-Base Metastasis in the MR Era].

BACKGROUND: Skull-base metastases frequently cause progressive ipsilateral disturbances of cranial nerves or pain, resulting in poor quality of life in patients with cancer. Magnetic resonance(MR)imaging is the method to detect skull-base metastases, which demonstrates focal lesions of low-intensity signal and enhancement on T1-weighted MR images. METHODS: We reviewed clinical data and MR images from 127 patients with skull-base metastases diagnosed at Shizuoka Cancer Center Hospital between August 2012 and November 2017. RESULTS: The most common primary site was the lung(44 patients), followed by the breast(34), colon(8), and prostate(8). The interval from diagnosis of the primary tumor to skull-base metastasis ranged from 0 to 276 months(median, 9 months). The interval was shortest with lung cancer(median, 0 month), and longest with carcinoma of the liver(median, 81 months). The most commonly affected site was the clivus(74%), followed by the petrous(35%), and the occipital condyle(18%). We classified 55 symptomatic patients into 6 clinical syndromes: orbital(18%), parasellar(7%), middle cranial fossa(24%), jugular foramen(7%), and occipital condyle(15%), described by Greenberg, and a new entity "clivopetrosal" syndrome presenting diplopia due to abducens palsy(20%). Of 47 patients who underwent irradiation, 29 patients(62%)achieved relief of their symptoms. Median overall survival after diagnosis of a skull-base metastasis was 7 months. Male sex and colon cancer were associated with poor prognosis. CONCLUSION: When a cancer patient presents with new-onset cranial nerve palsies or craniofacial pain, physicians need to identify skull-base metastases for prompt radiotherapy.

[Surgical Resection of Metastatic Brain Tumors:Risk of Local Recurrence and Leptomeningeal Dissemination, and Implications for Individualized Treatment].

Metastatic brain tumors are important complications in the overall management of cancers. We sought to determine the risk of local recurrence and leptomeningeal carcinomatosis(LC)in patients treated with surgical resection and adjuvant radiation therapy. We retrospectively reviewed 173 consecutive patients with metastatic brain tumors managed by surgical resection between 2002 and 2015 in a single institution. Eighty-seven percent of the patients underwent postoperative adjuvant radiotherapy. The median overall survival from surgery was 9.8 months. Thirty of 173 patients(17.3%)developed local recurrence and 14(8.1%)developed LC following surgery. Male sex(hazard ratio(HR): 2.8, 95% confidence interval(CI): 1.0-10.0), colon cancer(HR: 6.5, 95% CI: 2.2-24.2), and no postoperative radiation(HR: 5.6, 95% CI: 2.1-13.7)were identified as risk factors of local recurrence in multivariate analysis. Female sex(HR: 4.4, 95% CI: 1.2-20.9)and recursive partitioning analysis(RPA)class 3(HR: 1.0e+9, 95%CI: 1.7-)were identified as risk factors of LC in multivariate analysis. Our retrospective review showed that individualized treatment with surgical resection followed by adjuvant radiation therapy is a safe and feasible method to control metastatic brain tumors in the real world.

Brain metastasis in patients with metastatic breast cancer in the real world: a single-institution, retrospective review of 12-year follow-up.

PURPOSE: The data of 589 metastatic breast cancer (MBC) patients in a single institution were reviewed to determine the outcomes of patients with brain metastasis (BM) and assess the efficacy of BM screening. METHODS: The patients with BM among the 589 MBC patients who underwent treatment at Shizuoka Cancer Center (Shizuoka, Japan) from 09/2002 to 03/2014 were retrospectively analyzed. RESULTS: During the study period, BM developed in 187 (31.7%) patients. The tumor subtypes were as follows: luminal (hormone receptor [HR]+, HER2-), 44.9%; luminal-HER2 (HR+, HER2+), 14.9%; HER2 (HR-, HER2+), 21.3%; and triple-negative (TN), 16.0%. BM was detected in 48.6% of the patients by screening MRI. While 137 of 187 patients underwent local therapy, whole-brain irradiation was the most frequently applied therapy (63.5%). The median overall survival from the diagnosis of BM was as follows: luminal, 7.0 months (M); luminal-HER2, 13.3 M; HER2, 17.7 M; TN, 4.2 M. The HER2 status (hazard ratio [HR]: 0.58, 95% confidence interval [CI] 0.38-0.88) and nonprogressive extracranial lesion(s) (HR: 0.45, 95% CI 0.29-0.71) were identified as prognostic factors in a multivariate analysis. When limited to HER2-overexpressed MBC patients, the multivariate analysis revealed that non-progressive extracranial lesion(s) (HR: 0.20, 95% CI 0.088-0.47) and stereotactic irradiation (STI) as an initial treatment (HR: 0.18, 95% CI 0.061-0.56) were prognostic factors. CONCLUSIONS: Our retrospective review showed that early detection of BM by screening MRI, followed by STI, improved the prognosis of HER2-overexpressed MBC patients with BM. A further prospective randomized study is needed to confirm our findings.

A nationwide multi-institutional retrospective study to identify prognostic factors and develop a graded prognostic assessment system for patients with brain metastases from uterine corpus and cervical cancer.

BACKGROUND: The prevalence of brain metastases (BM) from uterine cancer has recently increased because of the improvement of overall survival (OS) of patients with uterine cancer due to its early detection and improved local control as a result of new effective treatments. However, little information is available regarding their clinical characteristics and prognosis, because oncologists have encountered BM from uterine cancer on rare occasions. METHODS: Records from 81 patients with uterine BM were collected from 10 institutes in Japan. These were used in a multi-institutional study to identify prognostic factors and develop a graded prognostic assessment (GPA) for patients with BM from uterine cancer. RESULTS: Median OS after the development of BM was 7 months (95% confidence interval, 4 to 10 months). Multivariate analysis revealed that there were survival differences according to the existence of extracranial metastases and number of BM. In the present uterine-GPA, a score of 0 was assigned to those patients with ≥5 BM and extracranial metastasis, a score of 2 was assigned to those patients with one to four BM or without extracranial metastasis, and a score of 4 was assigned to those patients with one to four BM and without extracranial metastasis. The median OS for patients with a uterine-GPA scores of 0, 2, and 4 was 3, 7, and 22 months, respectively. A survival analysis confirmed the presence of statistically significant differences between these groups (p < 0.05). The results were validated by data obtained from the National Report of Brain Tumor Registry of Japan. CONCLUSION: Uterine GPA incorporates two simple clinical parameters of high prognostic significance and can be used to predict the expected survival times in patients with BM from uterine cancer. Its use may help in determining an appropriate treatment for individual patients with BM.

Negative impact of leukoaraiosis on the incidence of brain metastases in patients with lung cancer.

The embolization of cancer cells to cerebral vessels occurs early in the multi-step metastatic process. We aimed to determine whether the presence of leukoaraiosis (LA) before treatment would predict the development of brain metastases (BM) in patients with lung cancer. Between January 2014 and June 2015, 1007 patients underwent initial (i.e., prior to any chemotherapy) or routine magnetic resonance (MR) imaging of the brain and exhibited no evidence of BM. Of these, 189 underwent repeat MR imaging; 34 of 189 patients (18%) developed new BM, whereas 155 patients did not. LA was retrospectively evaluated according to Fazekas scale on the initial screening MR images of these 189 patients. The frequency of grade 0 periventricular hyperintensity (PVH) was greater among patients with BM, compared to those without BM (p = 0.001). In a multivariate analysis, patients with adenocarcinoma (95% confidence interval [CI] 1.8-171.8) and small cell carcinoma (95% CI 1.4-172.4) respectively developed BM at 9.3- and 8.8-fold higher rates than those with squamous cell carcinoma. Patients with grade 0 PVH developed BM at a rate 3.5-, 8.6-, and 3.6-fold higher rates than those with grade 1 (95% CI 1.4-9.0), 2 (95% CI 2.4-41.9), and 3 (95% CI 1.02-15.0), respectively. Lung cancer patients with grade 0 PVH on initial MR images have a high subsequent incidence of BM. PVH is a useful method for evaluating risk of BM.

[Cotton-Dam Wash Cytology:A Technique for Diagnosis and Prevention of Dissemination during Resection of Metastatic Brain Tumors].

The management of brain metastases has been important in neurosurgical oncology. Resection of a brain metastasis carries an increased risk of leptomeningeal dissemination than other treatment modalities such as irradiation or pharmacotherapy. We have utilized intraoperative wash cytology of cotton patties covering the brain surface. The cytology information contributes to making a decision of postoperative whole brain radiation. We named the method as "cotton dam", that serves as a check and catch of neoplastic cells on the brain surface during resection surgery.

Expansive hematoma in delayed cerebral radiation necrosis in patients treated with T-DM1: a report of two cases.

BACKGROUND: Multiple new targeted agents have been developed for patients with human epidermal growth factor receptor type 2 (HER2) - positive breast cancer. Patients with HER2- positive breast cancer will develop brain metastases with greater incidence than patients with non-HER2 cancers, and many of them will undergo stereotactic radiosurgery (SRS) or other CNS radiotherapy. The interaction between radiation effects and new targeted agents is not well understood. We report two cases suggesting a novel adverse effect of T-DM1 (trastuzumab emtansine) on symptomatic enlargement of radiation necrosis (RN) after SRS. CASE PRESENTATION: Two patients with HER2-positive breast cancer had received SRS for single brain metastasis more than 5-years ago. They had been heavily treated for HER2-positive metastatic breast cancer (trastuzumab and pacritaxel, lapatinib and capecitabine). They initiated T-DM1 therapy for progressive systematic disease 5.5 years after stereotactic irradiation, when a small RN was recognized on brain MR images of each patient. The RN lesions increased in size and became symptomatic during 13 or 14 months of T-DM1 treatment. The patients underwent surgical resection of the lesion. Pathological examination revealed necrosis, hematoma, granulation tissue and telangiectasia without neoplastic cells. CONCLUSIONS: A potential enhancement of RN by T-DM1 in the brain may be one of important adverse events associated with the use of T-DM1 for patients after SRS. These cases highlight the need of careful follow-up when combining new systemic targeted therapies and SRS for brain metastases.

"Comet tail sign": A pitfall of post-gadolinium magnetic resonance imaging findings for metastatic brain tumors.

A highly enhanced cap attached to the surface of metastatic tumors in the brain parenchyma is occasionally encountered on magnetic resonance (MR) images. This atypical enhanced cap tends to occur in severe peritumoral edema and may produce the characteristic bulge of a metastatic mass lesion termed the "comet tail sign" (CTS). The purpose of this study was to demonstrate the features of the CTS using MR imaging and pathological findings, and to clarify its clinical relevance. We selected 21 consecutive cases of newly diagnosed metastases from MR imaging studies that demonstrated the CTS; all had diffuse peritumoral edema. The MR T2-weighted images showed similarly homogenous and high intensity signals in both the tail and peritumoral edema. Fourteen of the 21 patients underwent surgical resection of their tumors, and 12 tails were separately removed for pathological examination, no tumor cells which revealed. We speculate that the CTS does not contain neoplastic tissues but is observed as a result of the leakage of contrast medium from the tumor body into the interstitial space of the white matter. Although CTS is a peculiar and uncommon enhancement pattern, it has clinical significance in determining the extent of the margin for invasive local treatments, such as surgical resection or stereotactic radiotherapy; this is particularly true in and near the eloquent areas.

[Two Surgical Techniques for Metastatic Brain Tumors:Minimum Resection and Removal with Safety Margin].

Successful resection of cerebral metastases is based on good basic neurosurgical techniques, in conjunction with technologies for tumor localization. A clear understanding about the border zone pathology of metastatic lesions leads to two different techniques for safe and effective tumor removal. There is no capsule or pseudocapsule around the metastatic brain tumors. The border zone is widely heterogeneous, especially in lesions after stereotactic irradiation. Resection can be performed in a circumferential and en bloc fashion with sufficient safety margin of the normal brain in non-eloquent area. However, enucleation should be done without surrounding brain damage in and near eloquent areas.

[Leptomeningeal Dissemination in Patients with Pituitary Metastasis from Breast Cancer].

Pituitary metastases are uncommon complications of systemic cancer and account for only 1% of pituitary lesions. Breast cancer is one of the most common tumors to metastasize to the pituitary gland. A multidisciplinary approach that calls for close collaboration among oncologists, neurosurgeons, radiologists, and endocrinologists is mandatory for diagnosis and treatment of pituitary metastasis. From 2002 through 2013, 6 patients with pituitary metastases were treated at Shizuoka Cancer Center Hospital. The patients' age at presentation ranged from 45 to 75 years (average 59 years). Five of 6 patients had symptoms: anterior pituitary insufficiency in 4, diabetes insipidus in 3, and visual deficits in 2 patients. Five patients had other metastases at the time of presentation. Local irradiation to the metastatic lesion was adopted in 4, and whole brain irradiation was in 2 patients. In all cases, local control was achieved after irradiation, however, the pituitary insufficiency did not recover. Two of 4 patients treated with local irradiation suffered from meningeal dissemination within 5 months after treatment, and died at 8 and 11 months after diagnosis of pituitary metastasis, respectively. The patients treated with whole brain irradiation had longer survival periods. Early diagnosis, endocrinological management, and radiation therapy improve the quality of life in patients suffering from pituitary metastasis. Whole brain irradiation may be favorable in order to prevent meningeal dissemination.

[Posterior Reversible Encephalopathy Syndrome Associated with Cancer Therapy].

Posterior reversible encephalopathy syndrome(PRES)is a subacute neurological syndrome typically manifesting with headache, cortical blindness, and seizures. This syndrome is associated with risk factors such as malignant hypertension, eclampsia, and renal failure. Numerous case reports depict its occurrence in cancer patients. The direct causal mechanisms of PRES in cancer patients have not yet been identified. Cytotoxic chemotherapy may cause direct endothelial damage, which would impact the blood brain barrier. Angiogenesis inhibitors also cause elevation in blood pressure;this is significant, because PRES onset may be solely related to hypertension. An increased number of case reports involving new molecular targeted agent suggests that incidence of PRES as an oncological emergency may increase in the future.

Brain metastasis from hepatocellular carcinoma: The impact of radiotherapy on control of intracranial hemorrhage.

AIM: Brain metastasis from hepatocellular carcinoma (HCC) is rare and causes devastating outcomes with intracranial hemorrhage. We retrospectively analyzed the impact of radiotherapy in preventing hemorrhagic events among patients with brain metastasis from HCC. METHODS: Patients who underwent treatment for brain metastasis from HCC at our cancer center between January 2003 and December 2012 were identified from a prospectively compiled hospital database. Clinical characteristics were analyzed in patients with and without radiotherapy. RESULTS: Fifteen HCC patients with brain metastasis from HCC were classified into two groups: 11 patients underwent radiotherapy (group R) and four patients received best supportive care without radiotherapy (group N). Six patients (54.5%) in group R and four patients (100%) in group N showed intracranial hemorrhage at presentation of brain metastasis. No patients in group R experienced intracranial hemorrhage during follow up, although two patients in group N did. Median overall survival was 22.4 weeks (range, 5.42-69.1) in group R and 2.24 weeks (range, 1.0-15.4) in group N. CONCLUSION: For patients with brain metastasis from HCC, radiotherapy appears useful for controlling brain lesions, preventing intracranial hemorrhage and improving survival. Radiotherapy may contribute to control of intracranial tumor and prevention of intracranial hemorrhage for selected patients with brain metastasis from HCC.