Preliminary Study of Brain Glucose Metabolism Changes in Patients with Lung Cancer of Different Histological Types

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Wei-Ling Li

2015-01-01

Full Text Available Background: Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. Methods: One hundred and twenty patients with primary untreated lung cancer, who visited People′s Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases, squamous cell carcinoma (43 cases, and small-cell carcinoma (25 cases. The whole body 18F-fluorodeoxyglucose (18F-FDG positron emission tomography (PET/computed tomography (CT of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM software, with 50 age-matched and gender-matched healthy controls for comparison. Results: The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255 was larger than those in the adenocarcinoma group (total voxel value 1217 and squamous cell carcinoma group (total voxel value 1292. Conclusions: The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

The Vitamin D Receptor (VDR Gene Polymorphisms in Turkish Brain Cancer Patients

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Bahar Toptaş

2013-01-01

Full Text Available Objective. It has been stated that brain cancers are an increasingly serious issue in many parts of the world. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR gene polymorphisms and the risk of glioma and meningioma. Methods. We investigated the VDR Taq-I and VDR Fok-I gene polymorphisms in 100 brain cancer patients (including 44 meningioma cases and 56 glioma cases and 122 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (RF LP. Results. VDR Fok-I ff genotype was significantly increased in meningioma patients (15.9% compared with controls (2.5%, and carriers of Fok-I ff genotype had a 6.47-fold increased risk for meningioma cases. There was no significant difference between patients and controls for VDR Taq-I genotypes and alleles. Conclusions. We suggest that VDR Fok-I genotypes might affect the development of meningioma.

Conformity index for brain cancer patients

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Petkovska, Sonja; Tolevska, Cveta; Kraleva, Slavica; Petreska, Elena

2010-01-01

The purpose of this study is to present the level of conformity achieved by using 3D conformal radiotherapy for brain cancer patients. Conformity index is a helpful quantitative tool for assessing (evaluating) the quality of a treatment plan. Treatment plans made for ninety patients with brain tumor are worked on this paper. The patients are in supine position and immobilized with thermoplastic masks for the head. Computed tomography data sets with 5 mm scan thickness are used to create a 3D image. All structures of interest are contoured. In order to obtain an optimal dose distribution, treatment fields are fit around target volume with set-up margins of 7mm in each direction. The conformity index values are between 1.21 and 2.04. Value of 1.8 is exceeded in eighteen cases; nine of them are bigger than 1.9 and only three of them are above 2. The target volume for each of these extreme CI values is ideal covered (between 95% and 105% of the prescribed dose). The most acceptable conformity index value in this paper belongs to the plan with the lowest minimal dose (84.7%). It can be concluded that conformity index is necessary but not sufficient factor for assessing radiation treatment plan conformity. To be able to estimate the acceptability of some treatment plan in daily practice, additional information as minimal, maximal and mean dose into target volume, as well as health tissues coverage must be taken into account.(Author)

Predicting Brain Metastasis in Breast Cancer Patients: Stage Versus Biology.

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Azim, Hamdy A; Abdel-Malek, Raafat; Kassem, Loay

2018-04-01

Brain metastasis (BM) is a life-threatening event in breast cancer patients. Identifying patients at a high risk for BM can help to adopt screening programs and test preventive interventions. We tried to identify the incidence of BM in different stages and subtypes of breast cancer. We reviewed the clinical records of 2193 consecutive breast cancer patients who presented between January 1999 and December 2010. We explored the incidence of BM in relation to standard clinicopathological factors, and determined the cumulative risk of BM according to the disease stage and phenotype. Of the 2193 included women, 160 (7.3%) developed BM at a median follow-up of 5.8 years. Age younger than 60 years (P = .015), larger tumors (P = .004), lymph node (LN) positivity (P < .001), high tumor grade (P = .012), and HER2 positivity (P < .001) were associated with higher incidence of BM in the whole population. In patients who presented with locoregional disease, 3 factors independently predicted BM: large tumors (hazard ratio [HR], 3.60; 95% confidence interval [CI], 1.54-8.38; P = .003), axillary LN metastasis (HR, 4.03; 95% CI, 1.91-8.52; P < .001), and HER2 positivity (HR, 1.89; 95% CI, 1.0-3.41; P = .049). A Brain Relapse Index was formulated using those 3 factors, with 5-year cumulative incidence of BM of 19.2% in those having the 2 or 3 risk factors versus 2.5% in those with no or 1 risk factor (P < .001). In metastatic patients, 3 factors were associated with higher risk of BM: HER2 positivity (P = .007), shorter relapse-free interval (P < .001), and lung metastasis (P < .001). Disease stage and biological subtypes predict the risk for BM and subsequent treatment outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Trajectories of Symptom Clusters, Performance Status, and Quality of Life During Concurrent Chemoradiotherapy in Patients With High-Grade Brain Cancers.

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Kim, Sang-Hee; Byun, Youngsoon

Symptom clusters must be identified in patients with high-grade brain cancers for effective symptom management during cancer-related therapy. The aims of this study were to identify symptom clusters in patients with high-grade brain cancers and to determine the relationship of each cluster with the performance status and quality of life (QOL) during concurrent chemoradiotherapy (CCRT). Symptoms were assessed using the Memorial Symptom Assessment Scale, and the performance status was evaluated using the Karnofsky Performance Scale. Quality of life was assessed using the Functional Assessment of Cancer Therapy-General. This prospective longitudinal survey was conducted before CCRT and at 2 to 3 weeks and 4 to 6 weeks after the initiation of CCRT. A total of 51 patients with newly diagnosed primary malignant brain cancer were included. Six symptom clusters were identified, and 2 symptom clusters were present at each time point (ie, "negative emotion" and "neurocognitive" clusters before CCRT, "negative emotion and decreased vitality" and "gastrointestinal and decreased sensory" clusters at 2-3 weeks, and "body image and decreased vitality" and "gastrointestinal" clusters at 4-6 weeks). The symptom clusters at each time point demonstrated a significant relationship with the performance status or QOL. Differences were observed in symptom clusters in patients with high-grade brain cancers during CCRT. In addition, the symptom clusters were correlated with the performance status and QOL of patients, and these effects could change during CCRT. The results of this study will provide suggestions for interventions to treat or prevent symptom clusters in patients with high-grade brain cancer during CCRT.

A nomogram for predicting survival in patients with breast cancer brain metastasis.

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Huang, Zhou; Sun, Bing; Wu, Shikai; Meng, Xiangying; Cong, Yang; Shen, Ge; Song, Santai

2018-05-01

Brain metastasis (BM) is common in patients with breast cancer. Predicting patient survival is critical for the clinical management of breast cancer brain metastasis (BCBM). The present study was designed to develop and evaluate a prognostic model for patients with newly diagnosed BCBM. Based on the clinical data of patients with BCBM treated in the Affiliated Hospital of Academy of Military Medical Sciences (Beijing, China) between 2002 and 2014, a nomogram was developed to predict survival using proportional hazards regression analysis. The model was validated internally by bootstrapping, and the concordance index (c-index) was calculated. A calibration curve and c-index were used to evaluate discriminatory and predictive ability, in order to compare the nomogram with widely used models, including recursive partitioning analysis (RPA), graded prognostic assessment (GPA) and breast-graded prognostic assessment (Breast-GPA). A total of 411 patients with BCBM were included in the development of this predictive model. The median overall survival time was 14.1 months. Statistically significant predictors for patient survival included biological subtype, Karnofsky performance score, leptomeningeal metastasis, extracranial metastasis, the number of brain metastases and disease-free survival. A nomogram for predicting 1- and 2-year overall survival rates was constructed, which exhibited good accuracy in predicting overall survival with a concordance index of 0.735. This model outperformed RPA, GPA and Breast-GPA, based on the comparisons of the c-indexes. The nomogram constructed based on a multiple factor analysis was able to more accurately predict the individual survival probability of patients with BCBM, compared with existing models.

Risk of intracranial hemorrhage and cerebrovascular accidents in non-small cell lung cancer brain metastasis patients.

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Srivastava, Geetika; Rana, Vishal; Wallace, Suzy; Taylor, Sarah; Debnam, Matthew; Feng, Lei; Suki, Dima; Karp, Daniel; Stewart, David; Oh, Yun

2009-03-01

Brain metastases confer significant morbidity and a poorer survival in non-small cell lung cancer (NSCLC). Vascular endothelial growth factor-targeted antiangiogenic therapies (AAT) have demonstrated benefit for patients with metastatic NSCLC and are expected to directly inhibit the pathophysiology and morbidity of brain metastases, yet patients with brain metastases have been excluded from most clinical trials of AAT for fear of intracranial hemorrhage (ICH). The underlying risk of ICH from NSCLC brain metastases is low, but needs to be quantitated to plan clinical trials of AAT for NSCLC brain metastases. Data from MD Anderson Cancer Center Tumor Registry and electronic medical records from January 1998 to March 2006 was interrogated. Two thousand one hundred forty-three patients with metastatic NSCLC registering from January 1998 to September 2005 were followed till March 2006. Seven hundred seventy-six patients with and 1,367 patients without brain metastases were followed till death, date of ICH, or last date of study, whichever occurred first. The incidence of ICH seemed to be higher in those with brain metastasis compared with those without brain metastases, in whom they occurred as result of cerebrovascular accidents. However, the rates of symptomatic ICH were not significantly different. All ICH patients with brain metastasis had received radiation therapy for them and had been free of anticoagulation. Most of the brain metastasis-associated ICH's were asymptomatic, detected during increased radiologic surveillance. The rates of symptomatic ICH, or other cerebrovascular accidents in general were similar and not significantly different between the two groups. In metastatic NSCLC patients, the incidence of spontaneous ICH appeared to be higher in those with brain metastases compared with those without, but was very low in both groups without a statistically significant difference. These data suggest a minimal risk of clinically significant ICH for NSCLC

Brain metastases from colorectal cancer

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Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

2001-01-01

Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

Inclusion of brain in FDG PET/CT scanning techniques in cancer patients: Does it obviate the need for dedicated brain imaging?

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Purandare, Nilendu C.

2011-01-01

Metastases to the brain can affect about 10-20% cancer patients. Rising incidence of brain metastases in recent years is related to improved survival rates as a result of advances in cancer therapy and development of more sensitive diagnostic imaging techniques. In patients with extracranial malignancies detection of brain metastases is very important in deciding further diagnostic procedures, planning therapeutic strategies and also to ascertain prognosis. Computerized tomography (CT) and magnetic resonance imaging (MRI) are the modalities which have been traditionally used to assess metastatic disease to the central nervous system. It is generally accepted that MRI (contrast enhanced) is superior to CT scan (contrast enhanced) in the diagnosis of brain metastases. An inherently better soft tissue contrast resolution, stronger contrast enhancement, lack of bone artifacts and partial volume effects and direct multiplanar imaging enables MRI to pick up smaller sized as well as more number of metastases than a CT scan

Brain metastasis of breast cancer: clinical and radiologic findings

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An, Jin Kyung; Oh, Ki Keun; Kim, Eun Kyung; Chung, Tae Sub

2001-01-01

To analyse the clinical and radiologic findings brain metastasis of breast cancer. Sixty-one of 1399 patients in whom breast cancer was diagnosed between 1983 and 1999 were affected by brain metastasis. Among these 1399, the stage of the breast cancer, in descending order of frequency, was IIA (n=508), I (n=366), IIB (n=247), IIIA (n=189), IIIB (n=45), 0 (n=33) and IV (n=11). The stage of the 61 brain metastases, similarly ordered, was IIB (12.5%), IIA (3.9%), IIIA (3.1%), IIIB (2.2%) and I (0.8%). In all confirmed breast cancers, the age distribution, in descending order of frequency, was 40-49years (n=610), 50-59 (n=301), 30-39 (n=291), 60-69 (n=124), 20-19 (n=41), 70-79 (n=28), and 80-89 (n=4). The age distribution of brain metastasis was 20-29 (14.6%), 30-39 (7.9%), 50-59 (4.6%). 40-49 (2.6%) and 60-69 (1.6%). Imaging findings were available for 35 of the 61 patients affected by brain metastasis, and symptoms from brain among the 35, analysis of the symptoms of this metastasis, the site of the first distant metastasis to an extracranial or cranial organ, the interval from the diagnosis of breast cancer to brain metastasis, the interval from brain metastasis to death, and the difference in survival time between patients with initial and succeeding brain metastasis was undertaken. Brain CT findings were analysed in 29 cases and MRI findings in eight. The most common symptoms were headache and vomiting. Among the 35 brain metastasis patients for whom imaging findings were available, other systemic metastasis occurred in 22. Initial brain metastasis occurred in the remaining 13, and in seven of these there was also coincident organ metastasis, while six showed only brain metastasis, The most frequent intervals from the diagnosis of breast cancer to brain metastasis were 1-2 years(8/35) and 2-3years(8/35). Twenty-six of 35 patients died within one year of brain metastasis. Patients in whom this occurred later survived for longer than those in whom it occurred

Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

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Ostrom, Quinn T. [Department of Anthropology, Case Western Reserve University, Cleveland, OH (United States); McCulloh, Christopher [Case Western Reserve University School of Medicine, Cleveland, OH (United States); Chen, Yanwen; Devine, Karen; Wolinsky, Yingli, E-mail: qto@case.edu [Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH (United States)

2012-02-28

Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

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Ostrom, Quinn T.; McCulloh, Christopher; Chen, Yanwen; Devine, Karen; Wolinsky, Yingli

2012-01-01

Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

Family history of cancer in benign brain tumor subtypes versus gliomas

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Quinn eOstrom

2012-02-01

Full Text Available Purpose: Family history is associated with gliomas, but this association has not ben established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study (OBTS. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%, 78 meningioma (65%, 49 pituitary adenoma (73.1% and 152 glioma patients (58.2%. The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs and 95% confidence intervals (95% CI. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusions: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

Population-based outcomes after brain radiotherapy in patients with brain metastases from breast cancer in the Pre-Trastuzumab and Trastuzumab eras

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Karam, Irene; Hamilton, Sarah; Nichol, Alan; Woods, Ryan; Speers, Caroline; Kennecke, Hagen; Tyldesley, Scott

2013-01-01

To evaluate the survival of patients with human epidermal growth factor receptor 2 (HER2) positive and negative metastatic breast cancer irradiated for brain metastases before and after the availability of trastuzumab (T). Women diagnosed with brain metastasis from breast cancer in two eras between 2000 and 2007 (T-era, n = 441) and 1986 to 1992 (PreT-era, n = 307), treated with whole brain radiotherapy (RT) were identified. In the T-era, HER2 testing was part of routine clinical practice, and in the preT-era 128/307 (42%) cases had HER2 testing performed retrospectively on tissue microarrays. Overall survival (OS) was estimated using the Kaplan-Meier method and comparisons between eras used log-rank tests. In the preT- and T-era cohorts, the rate of HER2 positivity was 40% (176/441) and 26% (33/128) (p < 0.001). The median time from diagnosis to brain RT was longer in the preT-era (3.3 years versus 2.3 years, p < 0.001). Survival after brain RT was improved in the T-era compared to the preT-era (1-year OS 26% versus 12%, p < 0.001). The 1-year OS rate for HER2 negative patients was 20% in both eras (p = 0.97). Among HER2 positive patients, the 1-year OS in the preT-era was 5% compared to 40% in the T-era (p < 0.001). Distinct from patients with HER2 negative disease in whom no difference in survival after brain RT was observed over time, patients with HER2 positive brain metastases experienced significantly improved survival subsequent to the availability of trastuzumab

Systemic treatment after whole-brain radiotherapy may improve survival in RPA class II/III breast cancer patients with brain metastasis.

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Zhang, Qian; Chen, Jian; Yu, Xiaoli; Ma, Jinli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Chen, Xingxing; Guo, Xiaomao; Chen, Jiayi

2013-09-01

Whole brain radiotherapy (WBRT) is the most widely used treatment for brain metastasis (BM), especially for patients with multiple intracranial lesions. The purpose of this study was to examine the efficacy of systemic treatments following WBRT in breast cancer patients with BM who had different clinical characteristics, based on the classification of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) and the breast cancer-specific Graded Prognostic Assessment (Breast-GPA). One hundred and one breast cancer patients with BM treated between 2006 and 2010 were analyzed. The median interval between breast cancer diagnosis and identification of BM in the triple-negative patients was shorter than in the luminal A subtype (26 vs. 36 months, respectively; P = 0.021). Univariate analysis indicated that age at BM diagnosis, Karnofsky performance status/recursive partitioning analysis (KPS/RPA) classes, number of BMs, primary tumor control, extracranial metastases and systemic treatment following WBRT were significant prognostic factors for overall survival (OS) (P RPA classes and systemic treatments following WBRT remained the significant prognostic factors for OS. For RPA class I, the median survival with and without systemic treatments following WBRT was 25 and 22 months, respectively (P = 0.819), while for RPA class II/III systemic treatments significantly improved OS from 7 and 2 months to 11 and 5 months, respectively (P RPA class II/III patients.

Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report

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Elaimy, Ameer L.; Thumma, Sudheer R.; Lamm, Andrew F.; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

2012-01-01

Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient's primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival. PMID:23091748

Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer

International Nuclear Information System (INIS)

Sundaresan, P.; Yeghiaian, R.; Gebski, V.

2010-01-01

Full text: Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks ('early death') may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of'early death'. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with 'early death'. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of'early death'. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for 'early death'. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.

Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical setting

International Nuclear Information System (INIS)

Lekic, Mirko; Kovac, Viljem; Triller, Nadja; Knez, Lea; Sadikov, Aleksander; Cufer, Tanja

2012-01-01

Small cell lung cancer (SCLC) represents approximately 13 to 18% of all lung cancers. It is the most aggressive among lung cancers, mostly presented at an advanced stage, with median survival rates of 10 to12 months in patients treated with standard chemotherapy and radiotherapy. In approximately 15-20% of patients brain metastases are present already at the time of primary diagnosis; however, it is unclear how much it influences the outcome of disease according the other metastatic localisation. The objective of this analysis was to evaluate the median survival of SCLC patients treated by specific therapy (chemotherapy and/or radiotherapy) with regard to the presence or absence of brain metastases at the time of diagnosis. All SCLC patients have been treated in a routine clinical practice and followed up at the University Clinic Golnik in Slovenia. In the retrospective study the medical files from 2002 to 2007 were review. All patients with cytological or histological confirmed disease and eligible for specific oncological treatment were included in the study. They have been treated according to the guidelines valid at the time. Chemotherapy and regular followed-up were carried out at the University Clinic Golnik and radiotherapy at the Institute of Oncology Ljubljana. We found 251 patients eligible for the study. The median age of them was 65 years, majority were male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients (25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmed by a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. All patients received chemotherapy and all patients with confirmed brain metastases received whole brain irradiation (WBRT). The radiotherapy with radical dose at primary tumour was delivered to 27 patients with limited disease and they got 4–6 cycles of

Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

DEFF Research Database (Denmark)

Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

2011-01-01

Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...... cancer, 13 362 developed brain cancer, and 15 967 developed NHL. In nested studies using Cox regression models on individual participant data, we found that, after adult leukemia, the multivariate adjusted hazard ratios were 4.9 (95% confidence interval [CI], 2.8-8.5) for thyroid cancer, 1.9 (95% CI, 1...

(64)Cu-DOTA-trastuzumab PET imaging and HER2 specificity of brain metastases in HER2-positive breast cancer patients.

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Kurihara, Hiroaki; Hamada, Akinobu; Yoshida, Masayuki; Shimma, Schuichi; Hashimoto, Jun; Yonemori, Kan; Tani, Hitomi; Miyakita, Yasuji; Kanayama, Yousuke; Wada, Yasuhiro; Kodaira, Makoto; Yunokawa, Mayu; Yamamoto, Harukaze; Shimizu, Chikako; Takahashi, Kazuhiro; Watanabe, Yasuyoshi; Fujiwara, Yasuhiro; Tamura, Kenji

2015-01-01

The purpose of this study was to determine whether brain metastases from HER2-positive breast cancer could be detected noninvasively using positron emission tomography (PET) with (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab. PET was performed on five patients with brain metastases from HER2-positive breast cancer, at 24 or 48 h after the injection of approximately 130 MBq of the probe (64)Cu-DOTA-trastuzumab. Radioactivity in metastatic brain tumors was evaluated based on PET images in five patients. Autoradiography, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed in one surgical case to confirm HER2 specificity of (64)Cu-DOTA-trastuzumab. Metastatic brain lesions could be visualized by (64)Cu-DOTA-trastuzumab PET in all of five cases, which might indicated that trastuzumab passes through the blood-brain barrier (BBB). The HER2 specificity of (64)Cu-DOTA-trastuzumab was demonstrated in one patient by autoradiography, immunohistochemistry, and LC-MS/MS. Cu-DOTA-trastuzumab PET could be a potential noninvasive procedure for serial identification of metastatic brain lesions in patients with HER2-positive breast cancer. UMIN000004170.

Psychometric validation of the functional assessment of cancer therapy--brain (FACT-Br) for assessing quality of life in patients with brain metastases.

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Thavarajah, Nemica; Bedard, Gillian; Zhang, Liying; Cella, David; Beaumont, Jennifer L; Tsao, May; Barnes, Elizabeth; Danjoux, Cyril; Sahgal, Arjun; Soliman, Hany; Chow, Edward

2014-04-01

This study aimed to test the reliability, psychometric, and clinical validity of the use of the Functional Assessment of Cancer Therapy--Brain (FACT-Br) in patients with brain metastases. Patients with brain metastases were interviewed using the FACT-Br (including the FACT-general) 1 week prior to treatment. All patients completed a follow-up assessment 1 month post-treatment. Patients with a good performance status and receiving stereotactic radiosurgery completed an additional 1 week follow-up assessment after the initial baseline interview to assess test-retest reliability. Forty patients had complete 1 month follow-up data. Ten of these patients also completed the 1 week follow-up assessment from baseline. The median Karnofsky performance status of patients was 80 and the median age was 64 years. All subscales of the FACT-Br were found to be conceptually related (except for two correlations) using the following subscales: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), FACT-G total score, brain cancer subscale (BrC), and the FACT-Br total score. All FACT-Br scores demonstrated excellent reliability, except for the SWB scale which revealed good reliability. The FACT-Br scores showed no significant change in the quality of life (QoL) of patients from baseline to 1 month follow-up. The use of the combined FACT-G and FACT-Br Subscale to assess QoL specifically in patients with brain metastases has successfully undergone psychometric validation. Future clinical trials should use the FACT-G and FACT-Br Subscale to assess QoL in this patient population.

Validity of Three Recently Proposed Prognostic Grading Indexes for Breast Cancer Patients With Radiosurgically Treated Brain Metastases

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Yamamoto, Masaaki, E-mail: BCD06275@nifty.com [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Tokyo Women' s Medical University Medical Center E, Tokyo (Japan); Kawabe, Takuya [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences, Kyoto (Japan); Higuchi, Yoshinori [Department of Neurosurgery, Chiba University Graduate School of Medicine, Chiba (Japan); Sato, Yasunori [Clinical Research Center, Chiba University Graduate School of Medicine, Chiba (Japan); Barfod, Bierta E. [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Kasuya, Hidetoshi [Department of Neurosurgery, Tokyo Women' s Medical University Medical Center E, Tokyo (Japan); Urakawa, Yoichi [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan)

2012-12-01

Purpose: We tested the validity of 3 recently proposed prognostic indexes for breast cancer patients with brain metastases (METs) treated radiosurgically. The 3 indexes are Diagnosis-Specific Graded Prognostic Assessment (DS-GPA), New Breast Cancer (NBC)-Recursive Partitioning Analysis (RPA), and our index, sub-classification of RPA class II patients into 3 sub-classes (RPA class II-a, II-b and II-c) based on Karnofsky performance status, tumor number, original tumor status, and non-brain METs. Methods and Materials: This was an institutional review board-approved, retrospective cohort study using our database of 269 consecutive female breast cancer patients (mean age, 55 years; range, 26-86 years) who underwent Gamma Knife radiosurgery (GKRS) alone, without whole-brain radiation therapy, for brain METs during the 15-year period between 1996 and 2011. The Kaplan-Meier method was used to estimate the absolute risk of each event. Results: Kaplan-Meier plots of our patient series showed statistically significant survival differences among patients stratified into 3, 4, or 5 groups based on the 3 systems (P<.001). However, the mean survival time (MST) differences between some pairs of groups failed to reach statistical significance with all 3 systems. Thus, we attempted to regrade our 269 breast cancer patients into 3 groups by modifying our aforementioned index along with the original RPA class I and III, (ie, RPA I+II-a, II-b, and II-c+III). There were statistically significant MST differences among these 3 groups without overlap of 95% confidence intervals (CIs) between any 2 pairs of groups: 18.4 (95% CI = 14.0-29.5) months in I+II-a, 9.2 in II-b (95% CI = 6.8-12.9, P<.001 vs I+II-a) and 5.0 in II-c+III (95% CI = 4.2-6.8, P<.001 vs II-b). Conclusions: As none of the new grading systems, DS-GPS, BC-RPA and our system, was applicable to our set of radiosurgically treated patients for comparing survivals after GKRS, we slightly modified our system for breast cancer

Management of lung cancer brain metastasis: An overview

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Himanshu Srivastava

2017-01-01

Full Text Available With the improvements in systemic treatment for lung cancer, distant metastasis to sanctuary sites such as brain has become an increasingly more important issue. The management of these patients consists of supportive care and disease-directed treatment. Combined modality treatment (surgical resection or radiosurgery, followed by whole brain radiotherapy of brain metastases has greatly improved the local control of disease in patients with single lesion, good functional performance status, and controlled extracranial disease as demonstrated in prospective randomized studies. For patients with multiple brain metastases, conventional fractionated whole brain radiotherapy continues to be a standard and efficacious treatment. At present, experience with the use of molecularly targeted tyrosine kinase inhibitors in nonsmall cell lung cancer patients with activating mutations in the epidermal growth factor receptor gene and anaplastic lymphoma kinase gene is growing. However, their effectiveness in patients with brain metastases is not well established. In the arena of targeted therapies, vascular endothelial growth factor pathway inhibitors such as bevacizumab have shown some activity in brain metastases. Further prospective studies are necessary to facilitate selection of patient subpopulation for targeted agents in future studies.

Brain cancer treatment

International Nuclear Information System (INIS)

Gruszow, S.

1998-01-01

As soon as 1936 an American physicist proposed to treat certain forms of cancer by using the nuclear reaction: n + 10 B → 7 Li + 4 He where the alpha particles produced could destroy the DNA of surrounding cells. From 1951 to 1961 62 patients underwent this treatment for brain cancer. The results were unsatisfactory: the neutrons were not energetic enough to enter brain tissues deeply and were accompanied by strongly damaging gamma radiation. In Netherlands an installation using the high flux reactor of Petten has been set up. A highly focused neutron beam of about 10 keV with reduced gamma radiation is produced. The first step is to determine the limit exposure and the maximal permissible concentration of boron. (A.C.)

[Timing of Brain Radiation Therapy Impacts Outcomes in Patients with 
Non-small Cell Lung Cancer Who Develop Brain Metastases].

Science.gov (United States)

Wang, Yang; Fang, Jian; Nie, Jun; Dai, Ling; Hu, Weiheng; Zhang, Jie; Ma, Xiangjuan; Han, Jindi; Chen, Xiaoling; Tian, Guangming; Wu, Di; Han, Sen; Long, Jieran

2016-08-20

Radiotherapy combined with chemotherapy or molecular targeted therapy remains the standard of treatment for brain metastases from non-small cell lung cancer (NSCLC). The aim of this study is to determine if the deferral of brain radiotherapy impacts patient outcomes. Between May 2003 and December 2015, a total of 198 patients with brain metastases from NSCLC who received both brain radiotherapy and systemic therapy (chemotherapy or targeted therapy) were identified. The rate of grade 3-4 adverse reactions related to chemotherapy and radiotherapy had no significant difference between two groups. 127 patients received concurrent brain radiotherapy and systemic therapy, and 71 patients received deferred brain radiotherapy after at least two cycles of chemotherapy or targeted therapy. Disease specific-graded prognostic assessment was similar in early radiotherapy group and deferred radiotherapy group. Median overall survival (OS) was longer in early radiotherapy group compared to deferred radiotherapy group (17.9 months vs 12.6 months; P=0.038). Progression free survival (PFS) was also improved in patients receiving early radiotherapy compared to those receiving deferred radiotherapy (4.0 months vs 3.0 months; Pbrain metastases as any line therapy improved the OS (20.0 months vs 10.7 months; Pbrain radiotherapy may resulted in inferior OS in patients with NSCLC who develop brain metastases. A prospective multi-central randomized study is imminently needed.

CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2-neu-positive breast cancer.

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Sengupta, S; Rojas, R; Mahadevan, A; Kasper, E; Jeyapalan, S

2015-04-01

Nervous system relapse of patients with advanced HER2-neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood-brain barrier, as combination therapy to treat HER2-neu-positive breast cancer with brain metastases.

Relapsing pattern of brain metastasis after brain irradiation in small cell lung cancer

International Nuclear Information System (INIS)

Murakami, Masao; Kuroda, Yasumasa; Okamoto, Yoshiaki; Kono, Koichi; Yoden, Eisaku; Mori, Takeki

1997-01-01

Many reports concerning radiation therapy for brain metastasis have been published, and which of the various methods urged by these reports provide optional control is still controversial. According to developing diagnosis of metastasis in CNS, therapeutic problems should be referred. We reviewed 67 patients with small cell lung cancer and brain metastasis who underwent brain irradiation (Ave. 47 Gy/5W), and all 15 patients with brain relapse after the irradiation. Relapsing patterns in this clinical setting were divided into local regrowth in the same lesions and re-metastasis (reseeding) in other regions, by reviewing follow up CT and MRI studies. Total survival among 15 patients with brain relapse and 52 without relapse was longer in the former cases than the later: 1-, and 2-year survival (47/19%, 13/8%) and MST (10.8/5.7 months), from the initial brain irradiation. The concerned significant factors limited in younger age, low value of LDH and improvement of NF. Of the 15 patients with brain relapse, 4 developed local regrowth and 11 did re-metastasis. The period of remission since brain irradiation were 172±94.4 and 393±281 days, respectively. Lower number of brain metastasis and lower value of LDH were shown in re-metastasis patients. At the time of brain relapse, 11 patients had recurrence of carcinomatous meningitis. 4 patients were treated with whole brain re-irradiation. All patients died of cancer, including 12 of relapsing CNS diseases and 3 of primary lesion and hepatic metastasis. Leukoencephalopathy developed in 2 patients. Survival since the brain relapse was 2 to 238 days without significant difference in cases of local regrowth and re-metastasis. According to our data on relapsing pattern of brain metastasis after conventional fractionated brain irradiation with an objective dose of 50 Gy, 75% of brain relapse were re-metastasis, we appreciate this irradiation for initial brain metastasis if limited to the brain. (author)

Importance of Extracranial Disease Status and Tumor Subtype for Patients Undergoing Radiosurgery for Breast Cancer Brain Metastases

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Dyer, Michael A.; Kelly, Paul J. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Chen, Yu-Hui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (United States); Pinnell, Nancy E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Claus, Elizabeth B. [Harvard Medical School, Boston, MA (United States); Department of Neurosurgery, Brigham and Women' s Hospital, Boston, MA (United States); Yale University School of Medicine, New Haven, CT (United States); Lee, Eudocia Q. [Harvard Medical School, Boston, MA (United States); Center for Neuro-Oncology, Dana-Farber/Brigham and Women' s Center, Boston, MA (United States); Weiss, Stephanie E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Arvold, Nils D. [Harvard Radiation Oncology Program, Boston, MA (United States); Lin, Nancy U. [Harvard Medical School, Boston, MA (United States); Department of Medical Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)

2012-07-15

Purpose: In this retrospective study, we report on outcomes and prognostic factors for patients treated with stereotactic radiosurgery (SRS) for breast cancer brain metastases. Methods and Materials: We identified 132 consecutive patients with breast cancer who were treated with SRS for brain metastases from January 2000 through June 2010. We retrospectively reviewed records of the 51 patients with adequate follow-up data who received SRS as part of the initial management of their brain metastases. Overall survival (OS) and time to central nervous system (CNS) progression from the date of SRS were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results: Triple negative subtype was associated with CNS progression on univariate analysis (hazard ratio [HR] = 5.0, p = 0.008). On multivariate analysis, triple negative subtype (HR = 8.6, p = 0.001), Luminal B subtype (HR = 4.3, p = 0.03), and omission of whole-brain radiation therapy (HR = 3.7, p = 0.02) were associated with CNS progression. With respect to OS, Karnofsky Performance Status (KPS) {<=} 80% (HR = 2.0, p = 0.04) and progressive extracranial disease (HR = 3.1, p = 0.002) were significant on univariate analysis; KPS {<=} 80% (HR = 4.1, p = 0.0004), progressive extracranial disease (HR = 6.4, p < 0.0001), and triple negative subtype (HR = 2.9, p = 0.04) were significant on multivariate analysis. Although median survival times were consistent with those predicted by the breast cancer-specific Graded Prognostic Assessment (Breast-GPA) score, the addition of extracranial disease status further separated patient outcomes. Conclusions: Tumor subtype is associated with risk of CNS progression after SRS for breast cancer brain metastases. In addition to tumor subtype and KPS, which are incorporated into the Breast-GPA, progressive extracranial disease may be an important prognostic factor for OS.

The factors that have an impact on the development of brain metastasis in the patients with breast cancer

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Adem Dayan

2012-01-01

Conclusions: As the prognostic and predictive factors showing the development of brain metastasis in breast cancer patients may be identified, follow-up also including the brain is important in order to take preventive measures.

Epidural Brain Metastases in a Patient with Early Onset Pancreatic Cancer: A Case Report and Literature Review

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Aibek E. Mirrakhimov

2012-01-01

Full Text Available We present a case of early onset pancreatic cancer related extra-axial brain metastases. A 46-year-old Caucasian non-Jewish nonobese male with a history of PC diagnosed 3 months ago with metastases to the liver, omentum, malignant ascites, and a history of a pulmonary embolism was admitted to the hospital because of a new onset headache, nausea, and vomiting which started 2 days prior to the encounter. Brain MRI was ordered, which showed acute bihemispheric subdural hematomas and left hemispheric extra-axial heterogeneously enhancing lesions consisting with metastatic disease. The patient was started on ondansentron, metoclopramide, and dexamethasone. The cranial irradiation was started, and the patient’s headache and nausea significantly improved. There are only 9 published reports of extra-axial brain metastases related to the pancreatic cancer, whereas our paper is the first such case reported on a patient with epidural metastases and early onset pancreatic cancer.

Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer

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Fabian, Katalin; Gyulai, Marton; Furak, Jozsef

2016-01-01

Background: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. Methods: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive...... lung cancer patients with brain metastases. Results: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p ... of peritumoral brain edema (p

Identifying risk factors for brain metastasis in breast cancer patients: Implication for a vigorous surveillance program

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Lorraine Chow

2015-10-01

Conclusion: Chinese breast cancer patients with brain metastasis were more likely to have high-grade tumors and negative estrogen receptor status. A more vigorous surveillance program for the central nervous system should be considered for this group of patients.

Durable Clinical Benefit of Pertuzumab in a Young Patient with BRCA2 Mutation and HER2-Overexpressing Breast Cancer Involving the Brain

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Anna Koumarianou

2016-01-01

Full Text Available Patients with HER2-positive breast cancer and brain metastases have limited treatment options, and, as a result of their poor performance status and worse prognosis, they are underrepresented in clinical trials. Not surprisingly, these patients may not be fit enough to receive any active treatment and are offered supportive therapy. BRCA2 mutations are reported to be rarely associated with HER2-overexpressing advanced breast cancer and even more rarely with brain metastases at diagnosis. We report on a BRCA2-positive breast cancer patient with metastatic disease in multiple sites, including the brain, and poor performance status who exhibited an extraordinary clinical and imaging response to the novel anti-HER2 therapy pertuzumab after multiple lines of therapy including anti-HER2 targeting. To our knowledge, the clinicopathologic and therapeutic characteristics of this patient point to a unique case and an urgent need for further investigation of pertuzumab in patients with brain metastases.

External radiation of brain metastases from renal carcinoma: a retrospective study of 119 patients from the M. D. Anderson Cancer Center

International Nuclear Information System (INIS)

Wronski, Marek; Maor, Moshe H.; Davis, Brian J.; Sawaya, Raymond; Levin, Victor A.

1997-01-01

Purpose: Approximately 10% of patients with metastatic renal cell carcinoma are diagnosed with brain metastases. Most of these patients receive palliative radiotherapy and die of progressive brain metastatic disease. This retrospective study examines the M. D. Anderson Cancer Center experience with such patients who received only whole brain radiation therapy (WBRT). Methods and Materials: Records of 200 patients with brain metastases from renal carcinoma who were treated at M. D. Anderson Cancer Center between 1976 and 1993 were reviewed. Of these patients, 119 received WBRT only and constitute the basis of this study. Different prognostic factors were analyzed. Results: Overall median survival time from diagnosis of the brain metastases was 4.4 months. Multiple brain tumors were treated in 70 patients (58.8%) who had a survival of 3.0 months compared with 4.4 months for patients having a single brain metastasis (p = 0.043). Among 117 patients the causes of death were neurologic in 90 (76%), systemic cancer in 19 (16%), and unknown in 9 (8%). Survival rates at 6 months, 1 year, and 2 years, were 33.6, 16.8, and 5.9%, respectively. Patients in whom brain metastases were diagnosed synchronously with a renal primary (n = 24) had a median survival time of 3.4 months compared with 3.2 months for those 95 who were diagnosed metachronously (p < 0.79, NS). In the Cox multivariate analysis of 13 possible prognostic factors, only a single brain metastasis (p = 0.0329), lack of distant metastases at the time of diagnosis (p = 0.0056), and tumor diameter ≤ 2 cm (p < 0.0016) were statistically significant. Conclusion: These unsatisfactory results with WBRT suggest that more aggressive approaches, such as surgery or radiosurgery should be applied whenever possible

CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2–neu-positive breast cancer

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Sengupta, S.; Rojas, R.; Mahadevan, A.; Kasper, E.; Jeyapalan, S.

2015-01-01

Nervous system relapse of patients with advanced HER2–neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood–brain barrier, as combination therapy to treat HER2–neu-positive breast cancer with brain metastases. PMID:26634139

Changes of Brain Glucose Metabolism in the Pretreatment Patients with Non-Small Cell Lung Cancer: A Retrospective PET/CT Study.

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Zhang, Weishan; Ning, Ning; Li, Xianjun; Niu, Gang; Bai, Lijun; Guo, Youmin; Yang, Jian

2016-01-01

The tumor-to-brain communication has been emphasized by recent converging evidences. This study aimed to compare the difference of brain glucose metabolism between patients with non-small cell lung cancer (NSCLC) and control subjects. NSCLC patients prior to oncotherapy and control subjects without malignancy confirmed by 6 months follow-up were collected and underwent the resting state 18F-fluoro-D-glucose (FDG) PET/CT. Normalized FDG metabolism was calculated by a signal intensity ratio of each brain region to whole brain. Brain glucose metabolism was compared between NSCLC patients and control group using two samples t-test and multivariate test by statistical parametric maps (SPM) software. Compared with the control subjects (n = 76), both brain glucose hyper- and hypometabolism regions with significant statistical differences (Pbrain signal transduction pathways, and the hypometabolism regions (the left superior parietal lobule, bilateral inferior parietal lobule and left fusiform gyrus) lied in dorsal attention network and visuospatial function areas. The changes of brain glucose metabolism exist in NSCLC patients prior to oncotherapy, which might be attributed to lung-cancer related visceral sympathetic activation and decrease of dorsal attention network function.

Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer.

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Duchnowska, Renata; Loibl, Sibylle; Jassem, Jacek

2018-06-01

Approximately 30-50% of advanced HER2-positive breast cancer patients will develop central nervous system (CNS) metastases, with an annual risk of around 10%, and a half of them will die from brain progression. An increased risk of brain metastases is also seen in patients with early HER2-positive breast cancer administered curative therapy. Brain metastases in HER2-positive breast cancer patients usually constitute the first site of recurrence. The administration of anti-HER2 monoclonal antibodies, trastuzumab and pertuzumab, considerably delays the onset of symptomatic brain disease: however, the limited penetration of these compounds into the CNS hinders their efficacy. The small-molecule tyrosine kinase inhibitors of epidermal growth factor receptors family have established activity in HER2-positive breast cancer in both advanced disease and neoadjuvant setting. Favorable physico-chemical properties of these compounds allow them for a more efficient penetration through the blood-brain barrier, and hold the promise for more effective prevention and treatment of brain metastases. In this article we review the role of currently available or investigational HER2 tyrosine kinase inhibitors: lapatinib, neratinib, afatinib and tucatinib in the treatment of brain metastases in HER2-positive breast cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Characterization of Cancer Stem Cells in Patients with Brain ...

African Journals Online (AJOL)

Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a ...

Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain

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Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi Reddy; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M.; Fidler, Isaiah J.; Cantley, Lewis C.; Locasale, Jason W.; Weihua, Zhang

2014-01-01

Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain-metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the non-oxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBPs) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis, and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients. PMID:25511375

A delayed radiation necrosis of the brain in a patient with maxillary cancer

International Nuclear Information System (INIS)

Koike, Satoshi; Ogawa, Akihiro; Uno, Kinya; Okushi, Ikuyo; Inatsuki, Shinichi

1987-01-01

A 63-year-old male with maxillary cancer (T 4 N 0 M 0 ), who had been treated initially with 50 Gy of radiotherapy and 95 mg of Pepleomycin by intraarterial administration, was treated with 60 Gy of internal irradiation of Cesium source for the residual tumor. Furthermore, radical operation was performed to eradicate the tumor. A low density area (LDA) in the right temporal to occipital lobe of the brain was found by CT examination, when patient suffered from mental disturbance one year and 8 months postoperatively. Because a definite mass lesion could not be identified in the LDA, brain metastasis was ruled out. Patient was treated with a conservative medication using Glyceol, and his symptoms were successfully improved. (author)

Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis.

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Zhang, Qian; Chen, Jian; Yu, Xiaoli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Hu, Chaosu; Guo, Xiaomao; Sun, Jing; Chen, Jiayi

2016-09-01

We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

Clinical features of brain metastases in breast cancer: an implication for hippocampal-sparing whole-brain radiation therapy

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Wu S

2016-12-01

Full Text Available San-Gang Wu,1,* Jia-Yuan Sun,2,* Qin Tong,3 Feng-Yan Li,2 Zhen-Yu He2 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, 3Department of Radiation Oncology, The First Affiliated Hospital of University of South China, Hengyang, People’s Republic of China *These authors contributed equally to this work Objective: The objectives of this study were to describe the distribution of brain metastases (BM in breast cancer patients and investigate the risk factors for perihippocampal metastases (PHM. Patients and methods: Retrospective analysis of the clinicopathological characteristics and patterns of BM was performed. Associations between clinicopathological characteristics and PHM (the hippocampus plus 5 mm margin were evaluated using logistic regression analyses. Results: A total of 1,356 brain metastatic lesions were identified in 192 patients. Patients with 1–3 BM, 4–9 BM, and ≥10 BM accounted for 63.0%, 18.8%, and 18.2%, respectively. There were only 7 (3.6% patients with hippocampal metastases (HM and 14 (7.3% patients with PHM. On logistic regression, the number of BM was an independent risk factor for PHM. Patients with ≥10 BM had a significantly higher risk of PHM compared with those with <10 BM. Breast cancer subtype (BCS was not associated with PHM. The number of BM was significantly correlated with various BCSs. Patients with hormone receptor (HR+/human epidermal growth factor receptor 2 (HER2+, HR-/HER2+, and HR-/HER2- subtypes had a higher probability of ≥10 BM, relative to patients with an HR+/HER2- subtype. Conclusion: Our study suggests that a low incidence of PHM may be acceptable to perform hippocampal-sparing whole-brain radiation therapy for breast cancer patients

An active treatment of lung adenocarcinoma cancer with brain metastases: icotinib

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Zhang Y

2015-06-01

Full Text Available Ying Zhang, Huaping Tang, Jun Li, Meng Li Department of Respiration Medicine, Municipal Hospital, Qingdao, People’s Republic of China Abstract: Lung cancer has the highest mortality rate of all cancers world­wide. A total of 70%–75% of all lung cancers are non-small cell lung cancer (NSCLC with two-thirds presenting with locally advanced or metastatic disease at diagnosis. Brain metastasis is one of the most common problems in the management of NSCLC, worsening the prognosis and quality of life of NSCLC patients. The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs gefitinib and erlotinib have been tested in patients with NSCLC and brain metastasis. Icotinib is a new type of oral EGFR-TKI. In this report, we describe a patient with lung adenocarcinoma cancer with brain metastases who received icotinib treatment and kept satisfactory health-related quality of life for 1 year. Keywords: EGFR, non-small cell lung cancer, tyrosine kinase inhibitor

Brain imaging before primary lung cancer resection: a controversial topic.

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Hudson, Zoe; Internullo, Eveline; Edey, Anthony; Laurence, Isabel; Bianchi, Davide; Addeo, Alfredo

2017-01-01

International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England Clin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources. Our aim was to determine local practice based on historic outcomes in this patient cohort. This retrospective study took place in a regional thoracic surgical centre in the United Kingdom. Pathology records for all patients who had undergone lung resection with curative intent during the time period January 2012-December 2014 were analysed in October 2015. Electronic pathology and radiology reports were accessed for each patient and data collected about their histological findings, TNM stage, resection margins, and the presence of brain metastases on either pre-operative or post-operative imaging. From the dates given on imaging, we calculated the number of days post-resection that the brain metastases were detected. 585 patients were identified who had undergone resection of their lung cancer. Of these, 471 had accessible electronic radiology records to assess for the radiological evidence of brain metastases. When their electronic records were evaluated, 25/471 (5.3%) patients had radiological evidence of brain metastasis. Of these, five patients had been diagnosed with a brain metastasis at initial presentation and had undergone primary resection of the brain metastasis followed by resection of the lung primary. One patient had been diagnosed with both a primary lung and a primary bowel adenocarcinoma; on review of the case, it was felt that the brain metastasis was more likely to have

The Effect of Early Detection of Occult Brain Metastases in HER2-Positive Breast Cancer Patients on Survival and Cause of Death

International Nuclear Information System (INIS)

Niwinska, Anna; Tacikowska, Malgorzata; Murawska, Magdalena

2010-01-01

Purpose: The aim of the study is to evaluate disease-free survival, survival from the detection of brain metastases, overall survival, and cause of death in patients with occult brain metastases (Group I) vs. patients with symptomatic brain metastases (Group II). Methods and Materials: In 80 HER2-positive breast cancer patients, treated with trastuzumab and cytostatic agents for metastatic disease, magnetic resonance imaging screening of the brain was performed, and in 29 patients (36%) occult brain metastasis was detected (Group I). Whole-brain radiotherapy was delivered to Group I. This first group was compared with 52 patients who had symptomatic brain metastases (Group II) and was treated the same way, at the same clinic, during the same time period. Results: Median disease-free survival was 17 months in Group I and 19.9 months in Group II (p = 0.58). The median time interval between the dissemination of the disease and the detection of occult or symptomatic brain metastases was 9 and 15 months, respectively (p = 0.11). When the brain metastases were detected, the median survival was 9 and 8.78 months, respectively (p = 0.80). The median overall survival was 53 and 51 months, respectively (p = 0.94). In the group with occult brain metastases (Group I) 16% of patients died because of progression within the brain. In the group with symptomatic brain metastases (Group II) the rate of cerebral death was 48% (p = 0.009). Conclusions: Whole-brain radiotherapy of occult brain metastases in HER2-positive breast cancer patients with visceral dissemination produces a three-fold decrease in cerebral deaths but does not prolong survival.

Brain Cancer—Patient Version

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Brain cancer refers to growths of malignant cells in tissues of the brain. Tumors that start in the brain are called primary brain tumors. Tumors that spread to the brain are called metastatic brain tumors. Start here to find information on brain cancer treatment, research, and statistics.

Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer

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Nagla Abdel Karim

2015-01-01

Full Text Available Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%–14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%–80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting.

Brain cortical structural differences between non-central nervous system cancer patients treated with and without chemotherapy compared to non-cancer controls: a cross-sectional pilot MRI study using clinically indicated scans

Science.gov (United States)

Shiroishi, Mark S.; Gupta, Vikash; Bigjahan, Bavrina; Cen, Steven Y.; Rashid, Faisal; Hwang, Darryl H.; Lerner, Alexander; Boyko, Orest B.; Liu, Chia-Shang Jason; Law, Meng; Thompson, Paul M.; Jahanshad, Neda

2017-11-01

Background: Increases in cancer survival have made understanding the basis of cancer-related cognitive impairment (CRCI) more important. CRCI neuroimaging studies have traditionally used dedicated research brain MRIs in breast cancer survivors with small sample sizes; little is known about other non-CNS cancers. However, there is a wealth of unused data from clinically-indicated MRIs that could be used to study CRCI. Objective: Evaluate brain cortical structural differences in those with non-CNS cancers using clinically-indicated MRIs. Design: Cross-sectional Patients: Adult non-CNS cancer and non-cancer control (C) patients who underwent clinically-indicated MRIs. Methods: Brain cortical surface area and thickness were measured using 3D T1-weighted images. An age-adjusted linear regression model was used and the Benjamini and Hochberg false discovery rate (FDR) corrected for multiple comparisons. Group comparisons were: cancer cases with chemotherapy (Ch+), cancer cases without chemotherapy (Ch-) and subgroup of lung cancer cases with and without chemotherapy vs C. Results: Sixty-four subjects were analyzed: 22 Ch+, 23 Ch- and 19 C patients. Subgroup analysis of 16 LCa was also performed. Statistically significant decreases in either cortical surface area or thickness were found in multiple ROIs primarily within the frontal and temporal lobes for all comparisons. Limitations: Several limitations were apparent including a small sample size that precluded adjustment for other covariates. Conclusions: Our preliminary results suggest that various types of non-CNS cancers, both with and without chemotherapy, may result in brain structural abnormalities. Also, there is a wealth of untapped clinical MRIs that could be used for future CRCI studies.

The attitudes of brain cancer patients and their caregivers towards death and dying: a qualitative study

Directory of Open Access Journals (Sweden)

Kimmelman Jonathan

2007-11-01

Full Text Available Abstract Background Much money and energy has been spent on the study of the molecular biology of malignant brain tumours. However, little attention has been paid to the wishes of patients afflicted with these incurable tumours, and how this might influence treatment considerations. Methods We interviewed 29 individuals – 7 patients dying of a malignant brain tumor and 22 loved ones. One-on-one interviews were conducted according to a pre-designed interview guide. A combination of open-ended questions, as well as clinical scenarios was presented to participants in order to understand what is meaningful and valuable to them when determining treatment options and management approaches. The results were analyzed, coded, and interpreted using qualitative analytic techniques in order to arrive at several common overarching themes. Results Seven major themes were identified. In general, respondents were united in viewing brain cancer as unique amongst malignancies, due in large part to the premium placed on mental competence and cognitive functioning. Importantly, participants found their experiences, however difficult, led to the discovery of inner strength and resilience. Responses were usually framed within an interpersonal context, and participants were generally grateful for the opportunity to speak about their experiences. Attitudes towards religion, spirituality, and euthanasia were also probed. Conclusion Several important themes underlie the experiences of brain cancer patients and their caregivers. It is important to consider these when managing these patients and to respect not only their autonomy but also the complex interpersonal toll that a malignant diagnosis can have.

Whole-brain radiotherapy with 20 Gy in 5 fractions for brain metastases in patients with cancer of unknown primary (CUP)

International Nuclear Information System (INIS)

Rades, D.; Bohlen, G.; Dunst, J.; Lohynska, R.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.

2007-01-01

Background: Whole brain radiotherapy (WBRT) is the most common treatment for brain metastases. Survival of patients with cancer of unknown primary (CUP) presenting with brain metastases is extremely poor. A radiation program with a short overall treatment time (short-course RT) would be preferable to longer programs if it provides similar outcomes. This study compares short-course RT with 20 Gy in 5 fractions (5 x 4 Gy) given over 5 days to longer programs in CUP patients. Patients and Methods: Data regarding 101 CUP patients who received either short course WBRT (n = 34) with 5 x 4 Gy or long-course WBRT (n = 67) with 10 x 3 Gy given over 2 weeks or 20 x 2 Gy given over 4 weeks for brain metastases were analyzed retrospectively. Six additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, RPA-(Recursive Partitioning Analysis-)class. Results: On univariate analysis, the radiation program was not associated with survival (p = 0.88) nor intracerebral control (p = 0.36). Improved survival was associated with KPS ≥ 70 (p < 0.001), absence of extracranial metastases (p < 0.001), and RPA-class 1 (p < 0.001). On multivariate analyses, KPS (risk ratio [RR]: 4.55; p < 0.001), extracranial metastases (RR: 1.70; p = 0.018), and RPA-class (RR: 2.86; p < 0.001) maintained significance. On univariate analysis, KPS (p < 0.001) and RPA-class (p < 0.001) were significantly associated with intracerebral control. On multivariate analyses, KPS (RR: 2.72; p < 0.001) and RPA-class (RR: 2.09; p < 0.001) remained significant. Conclusion: Short-course WBRT with 5 x 4 Gy provided similar intracerebral control and survival as longer programs for the treatment of brain metastases in CUP patients. 5 x 4 Gy appears preferable because it is more convenient for patients. (orig.)

The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer

Science.gov (United States)

DENG, YANMING; FENG, WEINENG; WU, JING; CHEN, ZECHENG; TANG, YICONG; ZHANG, HUA; LIANG, JIANMIAO; XIAN, HAIBING; ZHANG, SHUNDA

2014-01-01

It has been demonstrated that erlotinib is effective in treating patients with brain metastasis from non-small-cell lung cancer. However, the number of studies determining the erlotinib concentration in these patients is limited. The purpose of this study was to measure the concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung carcinoma. Six patients were treated with the standard recommended daily dose of erlotinib (150 mg) for 4 weeks. All the patients had previously received chemotherapy, but no brain radiotherapy. At the end of the treatment period, blood plasma and cerebrospinal fluid samples were collected and the erlotinib concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The average erlotinib concentration in the blood plasma and the cerebrospinal fluid was 717.7±459.7 and 23.7±13.4 ng/ml, respectively. The blood-brain barrier permeation rate of erlotinib was found to be 4.4±3.2%. In patients with partial response (PR), stable disease (SD) and progressive disease (PD), the average concentrations of erlotinib in the cerebrospinal fluid were 35.5±19.0, 19.1±8.7 and 16.4±5.9 ng/ml, respectively. In addition, the efficacy rate of erlotinib for metastatic brain lesions was 33.3%, increasing to 50% in patients with EGFR mutations. However, erlotinib appeared to be ineffective in cases with wild-type EGFR. In conclusion, a relatively high concentration of erlotinib was detected in the cerebrospinal fluid of patients with brain metastases from non-small-cell lung cancer. Thus, erlotinib may be considered as a treatment option for this patient population. PMID:24649318

Changes in Brain Structural Networks and Cognitive Functions in Testicular Cancer Patients Receiving Cisplatin-Based Chemotherapy

NARCIS (Netherlands)

Amidi, Ali; Hosseini, S. M.Hadi; Leemans, Alexander; Kesler, Shelli R.; Agerbæk, Mads; Wu, Lisa M.; Zachariae, Robert

2017-01-01

Background: Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore

Value of brain computed tomography in small cell lung cancers

International Nuclear Information System (INIS)

Fernet, M.; Breau, J.L.; Goldlust, D.; Israel, L.

1988-01-01

88 patients with small cell lung cancer were studied. Brain scans were performed first at initial staging and repeated at regular intervals during the survey. The results confirm the limited value of brain scans in the detection of metastases in neurologically asymptomatic patients [fr

Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Harris, Sunit [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States); Chan, Michael D., E-mail: mchan@wfubmc.edu [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States); Lovato, James F. [Division of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University, Winston-Salem, North Carolina (United States); Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P. [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States)

2012-05-01

Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10-24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients' ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to

Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Freund, Derek; Zhang, Rui, E-mail: rzhang@marybird.com [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Department of Physics and Astronomy, Louisiana State University, Nicholson Hall, Tower Dr., Baton Rouge, LA 70810 (United States); Sanders, Mary [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Newhauser, Wayne [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Department of Physics and Astronomy, Louisiana State University, Nicholson Hall, Tower Dr., Baton Rouge, LA 70810 (United States)

2015-04-13

Cancer of the brain and central nervous system (CNS) is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN) can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT) compared to passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT). Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV) and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis.

Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

Directory of Open Access Journals (Sweden)

Derek Freund

2015-04-01

Full Text Available Cancer of the brain and central nervous system (CNS is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT compared to passively scattered proton therapy (PSPT and intensity modulated proton therapy (IMPT. Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis.

Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Harris, Sunit; Chan, Michael D.; Lovato, James F.; Ellis, Thomas L.; Tatter, Stephen B.; Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P.

2012-01-01

Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10–24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients’ ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to

Motexafin Gadolinium Combined With Prompt Whole Brain Radiotherapy Prolongs Time to Neurologic Progression in Non-Small-Cell Lung Cancer Patients With Brain Metastases: Results of a Phase III Trial

International Nuclear Information System (INIS)

Mehta, Minesh P.; Shapiro, William R.; Phan, See C.; Gervais, Radj; Carrie, Christian; Chabot, Pierre; Patchell, Roy A.; Glantz, Michael J.; Recht, Lawrence; Langer, Corey; Sur, Ranjan K.; Roa, Wilson H.; Mahe, Marc A.; Fortin, Andre; Nieder, Carsten; Meyers, Christina A.; Smith, Jennifer A.; Miller, Richard A.; Renschler, Markus F.

2009-01-01

Purpose: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. Methods and Materials: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. Results: Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% of the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed. Conclusion: In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable

The use and impact of quality of life assessment tools in clinical care settings for cancer patients, with a particular emphasis on brain cancer: insights from a systematic review and stakeholder consultations.

Science.gov (United States)

King, Sarah; Exley, Josephine; Parks, Sarah; Ball, Sarah; Bienkowska-Gibbs, Teresa; MacLure, Calum; Harte, Emma; Stewart, Katherine; Larkin, Jody; Bottomley, Andrew; Marjanovic, Sonja

2016-09-01

Patient-reported data are playing an increasing role in health care. In oncology, data from quality of life (QoL) assessment tools may be particularly important for those with limited survival prospects, where treatments aim to prolong survival while maintaining or improving QoL. This paper examines the use and impact of using QoL measures on health care of cancer patients within a clinical setting, particularly those with brain cancer. It also examines facilitators and challenges, and provides implications for policy and practice. We conducted a systematic literature review, 15 expert interviews and a consultation at an international summit. The systematic review found no relevant intervention studies specifically in brain cancer patients, and after expanding our search to include other cancers, 15 relevant studies were identified. The evidence on the effectiveness of using QoL tools was inconsistent for patient management, but somewhat more consistent in favour of improving patient-physician communication. Interviews identified unharnessed potential and growing interest in QoL tool use and associated challenges to address. Our findings suggest that the use of QoL tools in cancer patients may improve patient-physician communication and have the potential to improve care, but the tools are not currently widely used in clinical practice (in brain cancer nor some other cancer contexts) although they are in clinical trials. There is a need for further research and stakeholder engagement on how QoL tools can achieve most impact across cancer and patient contexts. There is also a need for policy, health professional, research and patient communities to strengthen information exchange and debate, support awareness raising and provide training on tool design, use and interpretation.

Outcomes of aggressive treatment in esophageal cancer patients with synchronous solitary brain metastasis.

Science.gov (United States)

Onal, Cem; Akkus Yildirim, Berna; Guler, Ozan Cem

2017-07-01

The aim of the present study was to investigate the outcomes of esophageal cancer (EC) patients with isolated synchronous brain oligometastasis (oligo-BM) treated with chemoradiotherapy (CRT) of the primary site and localized treatment of the BM with surgery, radiotherapy (RT) or radiosurgery. Of 125 EC patients investigated, seven patients (6%) had solitary BM. Six patients were diagnosed prior to, and one patient was diagnosed during, treatment. All patients were treated with neoadjuvant chemotherapy and whole-brain RT (WBRT) for BM. All but one patient received definitive CRT with a median RT dose of 50.4 Gy using conventional fractionation RT. The median age at diagnosis was 59 years (range, 48-77 years). Six patients succumbed to mortality, and one continued to receive systemic chemotherapy at the last visit. The median survival time of the patients was 18.9 months (range, 10.0-27.2 months). Median time to progression after completion of the treatments was 8 months (range, 3-9 months). Two patients had progression of the primary tumor, and one patient had progression of the BM. The neurological status of three patients with BM who were identified during the staging work-up did not deteriorate as a consequence of WBRT. In conclusion, the present study has demonstrated that aggressive treatment of the primary tumor and oligo-BM in patients with EC may prolong the survival time.

The Biology of Breast Cancer in Brain Metastasis

National Research Council Canada - National Science Library

Price, Janet

2001-01-01

...% of breast cancer patients and found at autopsy in 20 to 30%. Survival after detection of brain metastases can be short, and the therapy currently available only offers the hope of surviving one year to 20% of patients...

Temozolomide in patients with advanced non-small cell lung cancer with and without brain metastases. a phase II study of the EORTC Lung Cancer Group (08965).

NARCIS (Netherlands)

Dziadziuszko, R; Ardizzoni, A.; Postmus, P.E.; Smit, E.F.; Price, A; Debruyne, C.; Legrand, C; Giaccone, G.

2003-01-01

This study was performed to evaluate the activity of single-agent temozolomide in two groups of chemotherapy-naive non-small cell lung cancer (NSCLC) patients, with (12 patients) and without (13 patients) brain metastases (BM). Patients in both groups were treated with temozolomide 200 mg/m(2)/day,

Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets

Directory of Open Access Journals (Sweden)

Nitesh Rohatgi

2018-01-01

Full Text Available Breast cancer is a common cause of brain metastases, with metastases occurring in at least 10–16% of patients. Longer survival of patients with metastatic breast cancer and the use of better imaging techniques are associated with an increased incidence of brain metastases. Current therapies include surgery, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy and targeted therapies. However, the timing and appropriate use of these therapies is controversial and careful patient selection by using available prognostic tools is extremely important. Expert oncologist discussed on the mode of treatment to extend the OS and improve the quality of life ofHER2-positivebreast cancer patients with Solitary brain metastases. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Correlates of objectively measured sedentary behavior in cancer patients with brain metastases: an application of the theory of planned behavior.

Science.gov (United States)

Lowe, Sonya S; Danielson, Brita; Beaumont, Crystal; Watanabe, Sharon M; Baracos, Vickie E; Courneya, Kerry S

2015-07-01

The aim of this study is to examine the demographic, medical, and social-cognitive correlates of objectively measured sedentary behavior in advanced cancer patients with brain metastases. Advanced cancer patients diagnosed with brain metastases, aged 18 years or older, cognitively intact, and with palliative performance scale greater than 30%, were recruited from a Rapid Access Palliative Radiotherapy Program multidisciplinary brain metastases clinic. A cross-sectional survey interview assessed the theory of planned behavior variables and medical and demographic information. Participants wore activPAL™ (PAL Technologies Ltd, Glasgow, United Kingdom) accelerometers recording time spent supine, sitting, standing, and stepping during 7 days encompassing palliative whole brain radiotherapy treatments. Thirty-one patients were recruited. Correlates of median time spent supine or sitting in hours per day were instrumental attitude (i.e., perceived benefits) of physical activity (r = -0.42; p = 0.030) and affective attitude (i.e., perceived enjoyment) of physical activity (r = -0.43; p = 0.024). Moreover, participants who sat or were supine for greater than 20.7 h per day reported significantly lower instrumental attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.051) and affective attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.041). Finally, participants who were older than 60 years of age spent more time sitting or being supine. Instrumental attitude and affective attitude were the strongest correlates of objectively measured sedentary behavior. This information could inform intervention studies to increase physical activity in advanced cancer patients with brain metastases. Copyright © 2014 John Wiley & Sons, Ltd.

Clinical characteristics and treatment outcomes of patients with colorectal cancer who develop brain metastasis: a single institution experience.

Science.gov (United States)

Fountzilas, Christos; Chang, Katherine; Hernandez, Brian; Michalek, Joel; Crownover, Richard; Floyd, John; Mahalingam, Devalingam

2017-02-01

The development of brain metastasis (BM) in patients with colorectal cancer (CRC) is a rare and late event. We sought to investigate the clinical characteristics, disease course and safety using biologic agents in our patients with CRC who develop brain metastases. A retrospective review of patients with CRC with brain metastases treated at our institution from 01/2005-01/2015 was performed. Survival analysis was performed using the Kaplan-Meier method. Forty patients were included in the analysis. Median age was 55.5 years, 67.5% were males, and 28% had a KRAS mutation. Twenty-four percent were treatment-naive at the time of BM diagnosis. Patients had a median of two brain lesions. Sixty-five percent of the patients were treated with radiotherapy alone, 22.5% had both surgical resection and brain radiotherapy. Median overall survival was 3.2 months after development of BM. Overall survival was longer in patients who received combined modality local therapy compared to patients treated with surgical resection or radiotherapy alone. Patients who received systemic treatment incorporating biologics following development of BM had a median overall survival of 18.6 months. Overall, the administration of biologic agents was safe and well tolerated. In summary, BM is an uncommon and late event in the natural history of metastatic CRC. The ability to deliver combined-modality local brain therapy as well as availability of more systemic therapy options appear to lead to improved outcomes.

Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases

International Nuclear Information System (INIS)

Welzel, Grit; Fleckenstein, Katharina; Schaefer, Joerg; Hermann, Brigitte; Kraus-Tiefenbacher, Uta; Mai, Sabine K.; Wenz, Frederik

2008-01-01

Purpose: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. Methods and Materials: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. Results: Before therapy, prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. Conclusions: The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects

Mesothelin-specific Immune Responses Predict Survival of Patients With Brain Metastasis

DEFF Research Database (Denmark)

Zhenjiang, Liu; Rao, Martin; Luo, Xiaohua

2017-01-01

BACKGROUND: Patients with advanced malignancies, e.g. lung cancer, ovarian cancer or melanoma, frequently present with brain metastases. Clinical presentation and disease progression of cancer is in part shaped by the interaction of the immune system with malignant cells. Antigen-targeted immune ...... of the primary tumor origin. Analyses of immunological markers could potentially serve as prognostic markers in patients with brain metastases and help to select patients in need for adjunct, immunological, treatment strategies....... were tested for interferon gamma (IFN-γ) production, after which univariate and multivariate analyses (Cox stepwise regression model) were performed to identify independent clinical and immunological factors associated with patient survival. Patients were followed-up for at least 500days after surgery...

High-grade glioma in a patient with breast cancer

Directory of Open Access Journals (Sweden)

Che-Chao Chang

2014-07-01

Full Text Available Breast cancer is one of the most common origins of metastatic lesions in the central nervous system. Many patients with a breast cancer and concurrent brain tumor(s were diagnosed to have a metastatic lesion or lesions in the brain, based exclusively on their image findings without further pathologic verification, and received radiotherapy alone thereafter. It is, however, possible that a different pathology such as primary brain malignancy, which actually warrants a specific treatment modality, may occur in such patients with an already known malignancy. We, herein, reported a 61-year-old female patient who suffered from an anaplastic oligodendroglioma 1 year after her diagnosis of breast cancer. Demographic data, characteristic imaging findings, treatment, and outcome of the patient were discussed.

Results of radiotherapy for brain metastases from lung cancer

International Nuclear Information System (INIS)

Tatsuno, Ikuro; Tada, Akira; Takanaka, Tsuyoshi; Choto, Shuichi; Watanabe, Kihichiro

1987-01-01

Ten patients with brain metastases from lung cancer treated by irradiation between 1982 and 1985 were reviewed. Neurologic improvement by irradiation was obtained in all patients. The median duration of neurologic function control by irradiation and the median survival from the diagnosis of brain metastases were 9 months and 11 months, respectively. General performance status, neurologic function class and the presence or absence of other sites of metastases were important prognostic factors for survival. More than 50 Gy brain irradiation except small cell carcinoma was thought to be necessary to control the brain metastases. CT examinations were useful but limited to evaluate the effectiveness of irradiation. (author)

Results of radiotherapy for brain metastases from lung cancer

Energy Technology Data Exchange (ETDEWEB)

Tatsuno, Ikuro; Tada, Akira; Takanaka, Tsuyoshi; Choto, Shuichi; Watanabe, Kihichiro

1987-02-01

Ten patients with brain metastases from lung cancer treated by irradiation between 1982 and 1985 were reviewed. Neurologic improvement by irradiation was obtained in all patients. The median duration of neurologic function control by irradiation and the median survival from the diagnosis of brain metastases were 9 months and 11 months, respectively. General performance status, neurologic function class and the presence or absence of other sites of metastases were important prognostic factors for survival. More than 50 Gy brain irradiation except small cell carcinoma was thought to be necessary to control the brain metastases. CT examinations were useful but limited to evaluate the effectiveness of irradiation.

Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer

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Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

2018-01-01

Abstract This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population. A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study. The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study. This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population. PMID:29642161

Long-Term Survival in Patients With Synchronous, Solitary Brain Metastasis From Non-Small-Cell Lung Cancer Treated With Radiosurgery

International Nuclear Information System (INIS)

Flannery, Todd W.; Suntharalingam, Mohan; Regine, William F.; Chin, Lawrence S.; Krasna, Mark J.; Shehata, Michael K.; Edelman, Martin J.; Kremer, Marnie; Patchell, Roy A.; Kwok, Young

2008-01-01

Purpose: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). Patients and Methods: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. Results: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS ≥90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). Conclusions: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy

CXCR4/CXCL12 in Non-Small-Cell Lung Cancer Metastasis to the Brain

Directory of Open Access Journals (Sweden)

Sebastiano Cavallaro

2013-01-01

Full Text Available Lung cancer represents the leading cause of cancer-related mortality throughout the world. Patients die of local progression, disseminated disease, or both. At least one third of the people with lung cancer develop brain metastases at some point during their disease, even often before the diagnosis of lung cancer is made. The high rate of brain metastasis makes lung cancer the most common type of tumor to spread to the brain. It is critical to understand the biologic basis of brain metastases to develop novel diagnostic and therapeutic approaches. This review will focus on the emerging data supporting the involvement of the chemokine CXCL12 and its receptor CXCR4 in the brain metastatic evolution of non-small-cell lung cancer (NSCLC and the pharmacological tools that may be used to interfere with this signaling axis.

Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

Institute of Scientific and Technical Information of China (English)

Susanne Bartelt; Felix Momm; Christian Weissenberger; Johannes Lutterbach

2004-01-01

AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract.METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively.RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n = 0, stomach:n = 10, colorectal: n = 47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients.WBRTwas applied with daily fractions of 2 Gray (Gy) or 3 Gy to a total dose of 50 Gy or 30 Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6 mo vs8.0 mo for patients with primary tumors of the colon/rectum vs other primary tumors,respectively (P＜0.01, log-rank). Median overall survival for all patients with brain metastases (n = 916) was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms.Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P＜0.05, log-rank). In patients with gastrointestinal neoplasms (n = 57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for patients with multiple brain metastases (P＜0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70was 5.5 mo vs2.1 mo for patients with KPS ＜70 (P＜0.01,log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival.CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the

Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases.

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Freedman, Rachel A; Gelman, Rebecca S; Wefel, Jeffrey S; Melisko, Michelle E; Hess, Kenneth R; Connolly, Roisin M; Van Poznak, Catherine H; Niravath, Polly A; Puhalla, Shannon L; Ibrahim, Nuhad; Blackwell, Kimberly L; Moy, Beverly; Herold, Christina; Liu, Minetta C; Lowe, Alarice; Agar, Nathalie Y R; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F; Krop, Ian E; Wolff, Antonio C; Winer, Eric P; Lin, Nancy U

2016-03-20

Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥ 50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression--the threshold for success was five of 40 responders. Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients

BRCA1 Mutations Associated With Increased Risk of Brain Metastases in Breast Cancer: A 1: 2 Matched-pair Analysis.

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Zavitsanos, Peter J; Wazer, David E; Hepel, Jaroslaw T; Wang, Yihong; Singh, Kamaljeet; Leonard, Kara L

2018-05-18

Brain metastases (BM) occur in ∼5% of breast cancer patients. BRCA1-associated cancers are often basal-like and basal-like cancers are known to have a predilection for central nervous system metastases. We performed a matched-pair analysis of breast cancer patients with and without BRCA mutations and compared the frequency of BM in both groups. From a database of 1935 patients treated for localized breast cancer at our institution from 2009 to 2014 we identified 20 patients with BRCA1 or BRCA2 mutations and manually matched 40 patients without BRCA mutations accounting for age, stage, estrogen receptor expression, and human epidermal growth factor receptor 2 (HER2) expression. Comparisons of freedom from brain metastasis, brain metastasis-free survival, and overall survival were made using the log rank test. Testing for a basal-type phenotype using the immunohistochemistry definition (ER/PR/HER2 and either CK 5/6 or EGFR) was performed for BRCA patients who developed BM and their matched controls. We analyzed 60 patients: 20 BRCA and 40 were matched controls. Median follow-up was 37 and 49 months, respectively. Three years freedom from brain metastasis was 84% for BRCA patients and 97% for BRCA controls (P=0.049). Three years brain metastasis-free survival was 84% and 97% for the BRCA+ and controls, respectively (P=0.176). Mean time to brain failure was 11 months from diagnosis for the BRCA patients. All 3 BRCA1 patients who developed BM were of a basal-type triple negative phenotype. Breast cancer patients with germline BRCA1 mutations appear to have a shorter interval to brain progression while accounting for confounding factors.

Nanotherapeutic approaches for brain cancer management.

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Saenz del Burgo, Laura; Hernández, Rosa María; Orive, Gorka; Pedraz, Jose Luis

2014-07-01

Around the world, cancer remains one of the most important causes of morbidity and mortality. Worldwide, approximately 238,000 new cases of brain and other central nervous system tumors are diagnosed every year. Nanotherapeutic approaches hold tremendous potential for diagnosis and treatment of brain cancer, including the ability to target complex molecular cargoes to the tumor sites and the capacity of crossing the blood-brain barrier and accessing to the brain after systemic administration. A new generation of "smart" nanoparticles has been designed as novel targeted delivery devices for new therapies including gene therapy, anti-angiogenic and thermotherapy. This review highlights the latest research, opportunities and challenges for developing novel nanotherapeutics for treating brain cancers. This comprehensive review highlights the latest research results, opportunities and challenges for developing novel nanotherapeutics for treating brain cancers, with a special focus on "smart" nanoparticles as novel targeted delivery devices for new therapies including gene therapy, anti-angiogenic therapy and localized thermotherapy. © 2014.

American brain tumor patients treated with BNCT in Japan

International Nuclear Information System (INIS)

Laramore, G.E.; Griffin, B.R.; Spence, A.

1995-01-01

The purpose of this work is to establish and maintain a database for patients from the United States who have received BNCT in Japan for malignant gliomas of the brain. This database will serve as a resource for the DOE to aid in decisions relating to BNCT research in the United States, as well as assisting the design and implementation of clinical trials of BNCT for brain cancer patients in this country. The database will also serve as an information resource for patients with brain tumors and their families who are considering this form of therapy

Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

Directory of Open Access Journals (Sweden)

Couraud Pierre-Olivier

2009-07-01

Full Text Available Abstract Background The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BKCa channels in breast cancer metastasis and invasion. Methods We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A, non-metastatic breast cancer (MCF-7, non-brain metastatic breast cancer cells (MDA-MB-231, and brain-specific metastatic breast cancer cells (MDA-MB-361 to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX. Results The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Conclusion Determining the relative abundance of BKCa channel expression in breast

Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

International Nuclear Information System (INIS)

Khaitan, Divya; Sankpal, Umesh T; Weksler, Babette; Meister, Edward A; Romero, Ignacio A; Couraud, Pierre-Olivier; Ningaraj, Nagendra S

2009-01-01

The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BK Ca ) channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BK Ca channels in breast cancer metastasis and invasion. We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BK Ca channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A), non-metastatic breast cancer (MCF-7), non-brain metastatic breast cancer cells (MDA-MB-231), and brain-specific metastatic breast cancer cells (MDA-MB-361) to study whether BK Ca channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX). The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BK Ca channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Determining the relative abundance of BK Ca channel expression in breast cancer metastatic to brain and the mechanism of its

Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study.

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Chen, Bihong T; Sethi, Sean K; Jin, Taihao; Patel, Sunita K; Ye, Ningrong; Sun, Can-Lan; Rockne, Russell C; Haacke, E Mark; Root, James C; Saykin, Andrew J; Ahles, Tim A; Holodny, Andrei I; Prakash, Neal; Mortimer, Joanne; Waisman, James; Yuan, Yuan; Somlo, George; Li, Daneng; Yang, Richard; Tan, Heidi; Katheria, Vani; Morrison, Rachel; Hurria, Arti

2018-05-02

Cognitive decline is among the most feared treatment-related outcomes of older adults with cancer. The majority of older patients with breast cancer self-report cognitive problems during and after chemotherapy. Prior neuroimaging research has been performed mostly in younger patients with cancer. The purpose of this study was to evaluate longitudinal changes in brain volumes and cognition in older women with breast cancer receiving adjuvant chemotherapy. Women aged ≥ 60 years with stage I-III breast cancer receiving adjuvant chemotherapy and age-matched and sex-matched healthy controls were enrolled. All participants underwent neuropsychological testing with the US National Institutes of Health (NIH) Toolbox for Cognition and brain magnetic resonance imaging (MRI) prior to chemotherapy, and again around one month after the last infusion of chemotherapy. Brain volumes were measured using Neuroreader™ software. Longitudinal changes in brain volumes and neuropsychological scores were analyzed utilizing linear mixed models. A total of 16 patients with breast cancer (mean age 67.0, SD 5.39 years) and 14 age-matched and sex-matched healthy controls (mean age 67.8, SD 5.24 years) were included: 7 patients received docetaxel and cyclophosphamide (TC) and 9 received chemotherapy regimens other than TC (non-TC). There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group pre-chemotherapy (p > 0.05). Exploratory hypothesis generating analyses focusing on the effect of the chemotherapy regimen demonstrated that the TC group had greater volume reduction in the temporal lobe (change = - 0.26) compared to the non-TC group (change = 0.04, p for interaction = 0.02) and healthy controls (change = 0.08, p for interaction = 0.004). Similarly, the TC group had a decrease in oral reading recognition scores (change = - 6.94) compared to the non-TC group (change = - 1.21, p for

Lymphopenia: A new independent prognostic factor for survival in patients treated with whole brain radiotherapy for brain metastases from breast carcinoma

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Claude, Line; Perol, David; Ray-Coquard, Isabelle; Petit, Thierry; Blay, Jean-Yves; Carrie, Christian; Bachelot, Thomas

2005-01-01

Background and purpose: To determine overall survival (OS) and independent prognostic factors in patients with brain metastases (BM) from breast cancer treated by whole brain radiotherapy (WBR). Patients and methods: One hundred and twenty (120) women with BM, treated in a single French cancer center between 02/91 and 06/01, were reviewed. BM were confirmed by computed tomography or magnetic resonance imaging. Survival time was defined as the time interval from the date of BM to the date of death or last follow-up. A Cox proportional hazards regression model was used to determine significant prognostic factors in a multivariate analysis. Results: Surgery was followed by WBR in 5 patients. One hundred and four (104) patients received exclusive WBR, eight received concomitant chemo-radiation, and one received chemo-radiation after surgery. The median survival time was 5 months (95% CI: 3-7 months). In the multivariate analysis, performance status over 1 and lymphopenia (<0.7 G/L) were found to be independent prognostic factors for poor survival. Based on the number of these independent prognostic factors, we propose a predictive model for survival in brain metastatic cancer patients. Median survival was 7 months for patients presenting none or one poor prognosis factor at diagnosis versus 2 months for patients with 2 poor prognosis factors (p<0.0001) Conclusion: Brain metastases from breast cancer remain associated with very poor prognosis and there is a need for better treatment procedures. If confirmed in predictive models, the identification of prognostic subgroups, based on KPS and lymphopenia, among patients with BM from breast cancer would help physicians select patients for future clinical trials

Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases

Science.gov (United States)

Gelman, Rebecca S.; Wefel, Jeffrey S.; Melisko, Michelle E.; Hess, Kenneth R.; Connolly, Roisin M.; Van Poznak, Catherine H.; Niravath, Polly A.; Puhalla, Shannon L.; Ibrahim, Nuhad; Blackwell, Kimberly L.; Moy, Beverly; Herold, Christina; Liu, Minetta C.; Lowe, Alarice; Agar, Nathalie Y.R.; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F.; Krop, Ian E.; Wolff, Antonio C.; Winer, Eric P.; Lin, Nancy U.

2016-01-01

Purpose Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Patients and Methods Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression—the threshold for success was five of 40 responders. Results Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Conclusion Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies

Variation in 'fast-track' referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites.

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Zhou, Y; Mendonca, S C; Abel, G A; Hamilton, W; Walter, F M; Johnson, S; Shelton, J; Elliss-Brookes, L; McPhail, S; Lyratzopoulos, G

2018-01-01

In England, 'fast-track' (also known as 'two-week wait') general practitioner referrals for suspected cancer in symptomatic patients are used to shorten diagnostic intervals and are supported by clinical guidelines. However, the use of the fast-track pathway may vary for different patient groups. We examined data from 669 220 patients with 35 cancers diagnosed in 2006-2010 following either fast-track or 'routine' primary-to-secondary care referrals using 'Routes to Diagnosis' data. We estimated the proportion of fast-track referrals by sociodemographic characteristic and cancer site and used logistic regression to estimate respective crude and adjusted odds ratios. We additionally explored whether sociodemographic associations varied by cancer. There were large variations in the odds of fast-track referral by cancer (P<0.001). Patients with testicular and breast cancer were most likely to have been diagnosed after a fast-track referral (adjusted odds ratios 2.73 and 2.35, respectively, using rectal cancer as reference); whereas patients with brain cancer and leukaemias least likely (adjusted odds ratios 0.05 and 0.09, respectively, for brain cancer and acute myeloid leukaemia). There were sex, age and deprivation differences in the odds of fast-track referral (P<0.013) that varied in their size and direction for patients with different cancers (P<0.001). For example, fast-track referrals were least likely in younger women with endometrial cancer and in older men with testicular cancer. Fast-track referrals are less likely for cancers characterised by nonspecific presenting symptoms and patients belonging to low cancer incidence demographic groups. Interventions beyond clinical guidelines for 'alarm' symptoms are needed to improve diagnostic timeliness.

Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer

International Nuclear Information System (INIS)

Ge, Xiao-hui; Liu, Miao-ling; Lin, Qiang; Ren, Xiao-cang; Liu, Yue-e; Chen, Xue-ji; Wang, Dong-ying; Wang, Yong-qiang; Cao, Bin; Li, Zhi-gang

2013-01-01

Patients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer. Patients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT). From March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ 2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ 2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ 2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups. Compared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent

Management of brain metastasis in a patient with advanced epithelial ovarian carcinoma by gamma-knife radiosurgery.

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Nikolaoul, Marinos; Stamenković, Srdjan; Stergiou, Christos; Skarleas, Christos; Torrens, Michael

2015-01-01

Brain metastases from epithelial ovarian cancer (EOC) are rare events. We present a rare case of single ovarian cancer metastasis to the brain treated with gamma-knife radiosurgery (GKRS). A 65-year-old woman with advanced EOC presented with severe neurologic symptoms. A single brain metastasis of 3.2 cm with surrounding edema in the left parietal lobe was detected by brain magnetic resonance imaging (MRI) scan during the work-up. The decision to perform GKRS was due to a surgical inaccessibility of intracranial lesion. Twelve weeks after the procedure, the MRI scan showed reduction in the diameter of brain metastasis and surrounding edema and the patient returned to good mental and motor performance.The patient survived for 22 months following treatment and died from a progressive intra-abdominal disease. Prognosis of ovarian cancer patients with brain metastases is generally poor regardless of treatment. Our case shows that GKRS as primary treatment modality for the control of ovarian cancer metastases to the brain was effective and can be considered as a treatment of choice if international selection criteria are followed.

Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

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Evers, Patrick; Lee, Percy P; DeMarco, John; Agazaryan, Nzhde; Sayre, James W; Selch, Michael; Pajonk, Frank

2010-01-01

Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs

Treatment of brain metastases from primary lung cancer

International Nuclear Information System (INIS)

Ryan, Gail F.; Ball, David L.; Smith, Jennifer G.

1995-01-01

Purpose: A retrospective study of patients treated at the Peter MacCallum Cancer Institute for brain metastases from primary carcinoma of the lung is presented. Methods and Materials: The medical records of 416 patients with the diagnosis of primary carcinoma of the lung who presented with, or subsequently developed, brain metastases during the period January 1984 to December 1987 were reviewed. Information on a number of factors of potential prognostic significance (sex, age, histology, performance status and interval between diagnosis of the primary and brain metastases) was collected. Details of surgery, radiation and steroid usage were recorded, and any steroid side effects documented. Survival was calculated from the date of diagnosis of brain metastases. Stepwise regression based on Cox's proportional hazards model was used to determine significant prognostic factors affecting survival. Patients with and without steroid side effects were compared using Yate's corrected chi-square test. Results: The overall estimated median survival was only 3.3 months (95% confidence interval 2.9-3.7 months). Only two factors were found to be associated with a significantly improved survival--surgical intervention and good performance status. After taking these two factors into account, the dose of radiation used (< 30 Gy or ≥ 30 Gy) did not influence survival. There was a 3% incidence of gastric bleeding or perforation in patients taking steroids, with a 40% fatality rate. Predisposing factors to gastric side effects were a prior history of peptic ulcer and/or aspirin or nonsteroidal anti-inflammatory drug consumption. Conclusion: Radiation of brain metastases from primary lung cancer results in modest survival benefit. Radiation dose (< 30 Gy or ≥ 30 Gy) is not a significant determinant of survival. Other treatment modifications, such as concurrent radiation and chemotherapy, should be explored. Steroids should be used with caution as fatal side effects can occur

Prognostic factors for survival and intracerebral control after irradiation for brain metastases from gynecological cancer

NARCIS (Netherlands)

Rades, Dirk; Fischer, Dorothea; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.

2009-01-01

The most appropriate treatment for the individual patient with brain metastases from gynecological cancer is unclear. Most of these patients receive whole-brain radiotherapy (WBRT) alone. Prognostic factors predicting the outcomes of these patients may guide the physician to select the appropriate

Benefit of brain prophylactic irradiation in patients suffering from a small-cell bronchial cancer: retrospective study on 289 cases

International Nuclear Information System (INIS)

Assouline, A.; Tai, P.; Jancewicz, M.; Joseph, K.; Krzisch, C.; Yu, E.

2011-01-01

The authors report a study which aimed at determining the benefit of a brain prophylactic irradiation for patients suffering from a localized small-cell bronchial cancer and in partial response to the local-regional treatment of their disease. A retrospective analysis has been performed on a set of 289 patients who had been treated by chemo-radiotherapy with or without brain prophylactic irradiation between 1981 and 2007. Data are discussed in terms of remission level, survival with respect to the level of response to the local-regional treatment. Depending on this response level the irradiation increases or not the probability of global survival, or the probability of specific survival. Short communication

Altered intrinsic brain activity after chemotherapy in patients with gastric cancer: A preliminary study

International Nuclear Information System (INIS)

Kim, Hyun Gi; Shin, Na-Young; Bak, Yunjin; Lim, Soo Mee; Kim, Kyung Ran; Jung, Young-Chul; Han, Kyunghwa; Lee, Seung-Koo

2017-01-01

To characterize the pattern of altered intrinsic brain activity in gastric cancer patients after chemotherapy (CTx). Patients before and after CTx (n = 14) and control subjects (n = 11) underwent resting-state functional MRI (rsfMRI) at baseline and 3 months after CTx. Regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF) were calculated and compared between the groups using the two-sample t test. Correlation analysis was also performed between rsfMRI values (i.e., ReHo, ALFF, and fALFF) and neuropsychological test results. Patients showed poor performance in verbal memory and executive function and decreased rsfMRI values in the frontal areas even before CTx and showed decreased attention/working memory and executive function after CTx compared to the control subjects. In direct comparison of values before and after CTx, there were no significant differences in neuropsychological test scores, but decreased rsfMRI values were observed at the frontal lobes and right cerebellar region. Among rsfMRI values, lower ALFF in the left inferior frontal gyrus was significantly associated with poor performance of the executive function test. We observed decreased attention/working memory and executive function that corresponded to the decline of frontal region activation in gastric cancer patients who underwent CTx. (orig.)

Altered intrinsic brain activity after chemotherapy in patients with gastric cancer: A preliminary study

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyun Gi [Ajou University Medical Center, Department of Radiology, Ajou University School of Medicine, Suwon (Korea, Republic of); Shin, Na-Young [Ewha Womans University School of Medicine, Department of Radiology, Seoul (Korea, Republic of); Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea, Republic of); Bak, Yunjin; Lim, Soo Mee [Ewha Womans University School of Medicine, Department of Radiology, Seoul (Korea, Republic of); Kim, Kyung Ran; Jung, Young-Chul [Yonsei University College of Medicine, Department of Psychiatry, Seoul (Korea, Republic of); Han, Kyunghwa; Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea, Republic of)

2017-07-15

To characterize the pattern of altered intrinsic brain activity in gastric cancer patients after chemotherapy (CTx). Patients before and after CTx (n = 14) and control subjects (n = 11) underwent resting-state functional MRI (rsfMRI) at baseline and 3 months after CTx. Regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF) were calculated and compared between the groups using the two-sample t test. Correlation analysis was also performed between rsfMRI values (i.e., ReHo, ALFF, and fALFF) and neuropsychological test results. Patients showed poor performance in verbal memory and executive function and decreased rsfMRI values in the frontal areas even before CTx and showed decreased attention/working memory and executive function after CTx compared to the control subjects. In direct comparison of values before and after CTx, there were no significant differences in neuropsychological test scores, but decreased rsfMRI values were observed at the frontal lobes and right cerebellar region. Among rsfMRI values, lower ALFF in the left inferior frontal gyrus was significantly associated with poor performance of the executive function test. We observed decreased attention/working memory and executive function that corresponded to the decline of frontal region activation in gastric cancer patients who underwent CTx. (orig.)

Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs

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Thirugnanam Sivasakthivel

2013-02-01

Full Text Available Abstract Background The obligate intracellular protozoan parasite Toxoplasma gondii infects humans and other warm-blooded animals and establishes a chronic infection in the central nervous system after invasion. Studies showing a positive correlation between anti-Toxoplasma antibodies and incidences of brain cancer have led to the notion that Toxoplasma infections increase the risk of brain cancer. However, molecular events involved in Toxoplasma induced brain cancers are not well understood. Presentation of the hypothesis Toxoplasma gains control of host cell functions including proliferation and apoptosis by channelizing parasite proteins into the cell cytoplasm and some of the proteins are targeted to the host nucleus. Recent studies have shown that Toxoplasma is capable of manipulating host micro RNAs (miRNAs, which play a central role in post-transcriptional regulation of gene expression. Therefore, we hypothesize that Toxoplasma promotes brain carcinogenesis by altering the host miRNAome using parasitic proteins and/or miRNAs. Testing the hypothesis The miRNA expression profiles of brain cancer specimens obtained from patients infected with Toxoplasma could be analyzed and compared with that of normal tissues as well as brain cancer tissues from Toxoplasma uninfected individuals to identify dysregulated miRNAs in Toxoplasma-driven brain cancer cells. Identified miRNAs will be further confirmed by studying cancer related miRNA profiles of the different types of brain cells before and after Toxoplasma infection using cell lines and experimental animals. Expected outcome The miRNAs specifically associated with brain cancers that are caused by Toxoplasma infection will be identified. Implications of the hypothesis Toxoplasma infection may promote initiation and progression of cancer by modifying the miRNAome in brain cells. If this hypothesis is true, the outcome of this research would lead to the development of novel biomarkers and

Dynamic contrast-enhanced MR imaging pharmacokinetic parameters as predictors of treatment response of brain metastases in patients with lung cancer

Energy Technology Data Exchange (ETDEWEB)

Kuchcinski, Gregory; Duhal, Romain; Lalisse, Maxime; Dumont, Julien; Lopes, Renaud; Pruvo, Jean-Pierre; Leclerc, Xavier; Delmaire, Christine [University of Lille, CHU Lille, Department of Neuroradiology, Lille (France); Le Rhun, Emilie [University of Lille, CHU Lille, Department of Neurosurgery, Lille (France); Oscar Lambret Center, Department of Medical Oncology, Lille (France); Inserm U1192-PRISM-Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse, Lille (France); Cortot, Alexis B. [University of Lille, CHU Lille, Department of Thoracic Oncology, Lille (France); Drumez, Elodie [University of Lille, CHU Lille, Department of Biostatistics, Lille (France)

2017-09-15

To determine the diagnostic accuracy of pharmacokinetic parameters measured by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting the response of brain metastases to antineoplastic therapy in patients with lung cancer. Forty-four consecutive patients with lung cancer, harbouring 123 newly diagnosed brain metastases prospectively underwent conventional 3-T MRI at baseline (within 1 month before treatment), during the early (7-10 weeks) and midterm (5-7 months) post-treatment period. An additional DCE MRI sequence was performed during baseline and early post-treatment MRI to evaluate baseline pharmacokinetic parameters (K{sup trans}, k{sub ep}, v{sub e}, v{sub p}) and their early variation (∇K{sup trans}, ∇k{sub ep}, ∇v{sub e}, ∇v{sub p}). The objective response was judged by the volume variation of each metastasis from baseline to midterm MRI. ROC curve analysis determined the best DCE MRI parameter to predict the objective response. Baseline DCE MRI parameters were not associated with the objective response. Early ∇K{sup trans}, ∇v{sub e} and ∇v{sub p} were significantly associated with the objective response (p = 0.02, p = 0.001 and p = 0.02, respectively). The best predictor of objective response was ∇v{sub e} with an area under the curve of 0.93 [95% CI = 0.87, 0.99]. DCE MRI and early ∇v{sub e} may be a useful tool to predict the objective response of brain metastases in patients with lung cancer. (orig.)

Validity of two recently-proposed prognostic grading indices for lung, gastro-intestinal, breast and renal cell cancer patients with radiosurgically-treated brain metastases.

Science.gov (United States)

Yamamoto, Masaaki; Serizawa, Toru; Sato, Yasunori; Kawabe, Takuya; Higuchi, Yoshinori; Nagano, Osamu; Barfod, Bierta E; Ono, Junichi; Kasuya, Hidetoshi; Urakawa, Yoichi

2013-02-01

We tested the validity of two prognostic indices for stereotactic radiosurgically (SRS)-treated patients with brain metastases (BMs) from five major original cancer categories. The two indices are Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) and our Modified Recursive Partitioning Analysis (RPA). Forty-six hundred and eight BM patients underwent gamma knife SRS during the 1998-2011 period. Primary cancer categories were non-small cell lung cancer (NSCLC, 2827 patients), small cell lung cancer (SCLC, 460), gastro-intestinal cancer (GIC, 582), breast cancer (BC, 547) and renal cell cancer (RCC, 192). There were statistically significant survival differences among patients stratified into four groups based on the DS-GPA systems (p failed to reach statistical significance with this system. There were, however, statistically significant MST differences (p < 0.001) among the three groups without overlapping of 95 % CIs between any two pairs of groups with the Modified RPA system in all five categories. The DS-GPA system is applicable to our set of patients with NSCLC only. However, the Modified RPA system was shown to be applicable to patients with five primary cancer categories. This index should be considered when designing future clinical trials involving BM patients.

Management of brain metastasis in a patient with advanced epithelial ovarian carcinoma by gamma-knife radiosurgery

Directory of Open Access Journals (Sweden)

Nikolaou Marinos

2015-01-01

Full Text Available Introduction. Brain metastases from epithelial ovarian cancer (EOC are rare events. We present a rare case of single ovarian cancer metastasis to the brain treated with gamma-knife radiosurgery (GKRS. Case Outline. A 65-year-old woman with advanced EOC presented with severe neurologic symptoms. A single brain metastasis of 3.2 cm with surrounding edema in the left parietal lobe was detected by brain magnetic resonance imaging (MRI scan during the work-up. The decision to perform GKRS was due to a surgical inaccessibility of intracranial lesion. Twelve weeks after the procedure, the MRI scan showed reduction in the diameter of brain metastasis and surrounding edema and the patient returned to good mental and motor performance. The patient survived for 22 months following treatment and died from a progressive intra-abdominal disease. Prognosis of ovarian cancer patients with brain metastases is generally poor regardless of treatment. Conclusion. Our case shows that GKRS as primary treatment modality for the control of ovarian cancer metastases to the brain was effective and can be considered as a treatment of choice if international selection criteria are followed.

Cognitive and brain structural changes in a lung cancer population.

Science.gov (United States)

Simó, Marta; Root, James C; Vaquero, Lucía; Ripollés, Pablo; Jové, Josep; Ahles, Tim; Navarro, Arturo; Cardenal, Felipe; Bruna, Jordi; Rodríguez-Fornells, Antoni

2015-01-01

No study has examined structural brain changes specifically associated with chemotherapy in a lung cancer population. The aim of this cross-sectional study was to assess differences in brain structure between small-cell lung cancer patients (C+) following chemotherapy, non-small-cell lung cancer patients (C-) before chemotherapy and healthy controls (HC). Twenty-eight small-cell lung cancer patients underwent a neuropsychological assessment and a structural magnetic resonance imaging, including T1-weighted and diffusion tensor imaging to examine gray matter density and white matter (WM) integrity, respectively, 1 month following completion of platinum-based chemotherapy. This group was compared with 20 age and education-matched non-small-cell lung cancer patients before receiving chemotherapy and 20 HC. Both C+ and C- groups exhibited cognitive impairment compared with the HC group. The C+ group performed significantly worse than HC in verbal fluency and visuospatial subtests; C- performed significantly worse than both C+ and HC in verbal memory. Voxel-based morphometry analysis revealed lower gray matter density in the insula and parahippocampal gyrus bilaterally, and left anterior cingulate cortex in C+ compared with HC. Diffusion tensor imaging indices showed focal decreased WM integrity in left cingulum and bilateral inferior longitudinal fasciculus in the C+ group and more widespread decreased integrity in the C- group compared with the HC group. This study demonstrates that lung cancer patients exhibit cognitive impairment before and after chemotherapy. Before the treatment, C- showed verbal memory deficits as well as a widespread WM damage. Following treatment, the C+ group performed exhibited lower visuospatial and verbal fluency abilities, together with structural gray matter and WM differences in bilateral regions integrating the paralimbic system.

Variation in ‘fast-track’ referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites

Science.gov (United States)

Zhou, Y; Mendonca, S C; Abel, G A; Hamilton, W; Walter, F M; Johnson, S; Shelton, J; Elliss-Brookes, L; McPhail, S; Lyratzopoulos, G

2018-01-01

Background: In England, ‘fast-track’ (also known as ‘two-week wait’) general practitioner referrals for suspected cancer in symptomatic patients are used to shorten diagnostic intervals and are supported by clinical guidelines. However, the use of the fast-track pathway may vary for different patient groups. Methods: We examined data from 669 220 patients with 35 cancers diagnosed in 2006–2010 following either fast-track or ‘routine’ primary-to-secondary care referrals using ‘Routes to Diagnosis’ data. We estimated the proportion of fast-track referrals by sociodemographic characteristic and cancer site and used logistic regression to estimate respective crude and adjusted odds ratios. We additionally explored whether sociodemographic associations varied by cancer. Results: There were large variations in the odds of fast-track referral by cancer (P<0.001). Patients with testicular and breast cancer were most likely to have been diagnosed after a fast-track referral (adjusted odds ratios 2.73 and 2.35, respectively, using rectal cancer as reference); whereas patients with brain cancer and leukaemias least likely (adjusted odds ratios 0.05 and 0.09, respectively, for brain cancer and acute myeloid leukaemia). There were sex, age and deprivation differences in the odds of fast-track referral (P<0.013) that varied in their size and direction for patients with different cancers (P<0.001). For example, fast-track referrals were least likely in younger women with endometrial cancer and in older men with testicular cancer. Conclusions: Fast-track referrals are less likely for cancers characterised by nonspecific presenting symptoms and patients belonging to low cancer incidence demographic groups. Interventions beyond clinical guidelines for ‘alarm’ symptoms are needed to improve diagnostic timeliness. PMID:29182609

Boron-neutron capture therapy for incurable cancer and inoperable brain tumors

International Nuclear Information System (INIS)

Hatanaka, Hiroshi

1993-01-01

Recent advances in cancer diagnosis and treatment have not yet improved the survival rate of patients with cancers of the brain, liver, etc. In these organs, an extirpation of the organ, which can be done for stomach, breast, cervix, lung, etc. is not allowed, and this fact is the cause of poor therapeutic results. Boron-neutron capture therapy (BNCT) utilizes the nuclear reaction which will take place between the boron-10 (loaded in the cancer cells artificially) and the thermal neutrons (delivered by reactors). The secondary radiations, helium and lithium hit the cancer cell itself and cause the death of the cancer cell while sparing the surrounding normal cells. BNCT is now being tried also by Oda of Kyoto University (9 cases) and by Nakagawa of Tokushima University (7 cases). It has been tried by Mishima (Kobe University) on 12 skin melanoma patients, proving satisfactory local control of the melanomas. Mercaptoundecahydrododecaborate (BHS) and boronophenylalanine (BPA) have been tried for brain tumors and for melanoma. For cancers of the liver and abdominal viscerae, antibody to the tumor specific antigen has been considered a good carrier of boron-10. Surgeons Takahashi, Fujii, Fujii, Yanagie, and Sekiguchi and immunologist Nariuchi of Tokyo University have been involved in the research and have obtained encouraging results in animals. Hatanaka has been proving good effect of BNCT upon giant cerebral arteriovenous malformation (AVM) and skull base meningioma. These diseases, although pathologically benign, have posed difficult problems in neurosurgery. It will be exciting good news to the patients. In conclusion, BNCT appears to be a good means to treat difficult lesions in the brain and other organs which defy sophisticated modern therapeutic means. (author)

Correlation between quantitative HER-2 protein expression and risk for brain metastases in HER-2+ advanced breast cancer patients receiving trastuzumab-containing therapy.

Science.gov (United States)

Duchnowska, Renata; Biernat, Wojciech; Szostakiewicz, Barbara; Sperinde, Jeff; Piette, Fanny; Haddad, Mojgan; Paquet, Agnes; Lie, Yolanda; Czartoryska-Arłukowicz, Bogumiła; Wysocki, Piotr; Jankowski, Tomasz; Radecka, Barbara; Foszczynska-Kłoda, Małgorzata; Litwiniuk, Maria; Debska, Sylwia; Weidler, Jodi; Huang, Weidong; Buyse, Marc; Bates, Michael; Jassem, Jacek

2012-01-01

Patients with human epidermal growth factor receptor (HER)-2+ breast cancer are at particularly high risk for brain metastases; however, the biological basis is not fully understood. Using a novel HER-2 assay, we investigated the correlation between quantitative HER-2 expression in primary breast cancers and the time to brain metastasis (TTBM) in HER-2+ advanced breast cancer patients treated with trastuzumab. The study group included 142 consecutive patients who were administered trastuzumab-based therapy for HER-2+ metastatic breast cancer. HER-2/neu gene copy number was quantified as the HER-2/centromeric probe for chromosome 17 (CEP17) ratio by central laboratory fluorescence in situ hybridization (FISH). HER-2 protein was quantified as total HER-2 protein expression (H2T) by the HERmark® assay (Monogram Biosciences, Inc., South San Francisco, CA) in formalin-fixed, paraffin-embedded tumor samples. HER-2 variables were correlated with clinical features and TTBM was measured from the initiation of trastuzumab-containing therapy. A higher H2T level (continuous variable) was correlated with shorter TTBM, whereas HER-2 amplification by FISH and a continuous HER-2/CEP17 ratio were not predictive (p = .013, .28, and .25, respectively). In the subset of patients that was centrally determined by FISH to be HER-2+, an above-the-median H2T level was significantly associated with a shorter TTBM (hazard ratio, [HR], 2.4; p = .005), whereas this was not true for the median HER-2/CEP17 ratio by FISH (p = .4). Correlation between a continuous H2T level and TTBM was confirmed on multivariate analysis (HR, 3.3; p = .024). These data reveal a strong relationship between the quantitative HER-2 protein expression level and the risk for brain relapse in HER-2+ advanced breast cancer patients. Consequently, quantitative assessment of HER-2 protein expression may inform and facilitate refinements in therapeutic treatment strategies for selected subpopulations of patients in this

Palliative care in patients who receive whole brain radiotherapy for ...

African Journals Online (AJOL)

Background: Brain Metastases is a devastating complication of Cancer affecting 10-50% of patients with systemic disease. It by far outnumbers primary Brain tumor in a 10:1 ratio. Aims and Objective: To determine the age distribution, gender distribution, tumor of origin, commonest radiotherapy regimen and median survival ...

Treatment strategies for lung cancer brain metastases

International Nuclear Information System (INIS)

Nakade, Masaharu; Kohno, Keijirou; Watanabe, Hiroyoshi

1997-01-01

Forty-one patients suffered initial relapses with brain metastasis after surgery for non-small lung cancer at our hospital between 1978 and 1995. These patients were a total of 8.4% of all cases of surgical removal, and had an average relapse period of 8.6 months ± 8.0 months after surgery on the primary lesions. Of these, surgical removal of metastasized lesions was performed on 18 patients (43%), in which the 5-year post-operative survival rate was 35.7%, and the median survival time was good at 28 months. It was found that the survival period was significantly extended in the group whose relapse period was less than one year after surgery on the primary lesions, and in the group who received cranial irradiation post-operatively on the metastasized brain lesion. Following surgery on the metastasized lesion, second relapses occurred in nine patients, and six patients suffered from second relapses in the brain, of which four did not receive cranial irradiation post-operatively. Cases of radiotherapy in patients of 70 years of age or more frequently manifested post-radiotherapy subacute neuropathy. From the above, it is thought that the following procedures should be adopted: Periodic examination for brain metastasis during the 24 months following surgery for non-small cell lung carcinoma for purposes of early detection; in cases where brain metastasis is detected, if no metastasis is identified in other organs, a policy of surgical removal should be adopted where possible; and, in cases of 70 years of age or less following surgery on the metastasized lesion, cranial irradiation should be considered. (author)

Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

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VandenBerg Scott R

2010-04-01

Full Text Available Abstract Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3% cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

Variations of blood glucose in cancer patients during chemotherapy

African Journals Online (AJOL)

2016-05-23

May 23, 2016 ... Purpose: The aim of this study was to analyze the blood glucose (BG) variations in cancer patients .... cancer, brain tumor, cervical cancer, and leukemia were the ... excess glucose supply for these glucose‑hungry cells and it.

PET/MRI in cancer patients

DEFF Research Database (Denmark)

Kjær, Andreas; Loft, Annika; Law, Ian

2013-01-01

Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear...... described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision...... that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations....

High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats.

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Wu, Yingjen Jeffrey; Pagel, Michael A; Muldoon, Leslie L; Fu, Rongwei; Neuwelt, Edward A

2017-08-01

Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Prolonged survival after resection and radiotherapy for solitary brain metastases from non-small-cell lung cancer

International Nuclear Information System (INIS)

Chee, R. J.; Bydder, S.; Cameron, F.

2007-01-01

Selected patients with brain metastases from non-small-cell lung cancer benefit from aggressive treatment. This report describes three patients who developed solitary brain metastases after previous resection of primary adenocarcinoma of the lung. Each underwent surgical resection of their brain metastasis followed by cranial irradiation and remain disease free 10 or more years later. Two patients developed cognitive impairment approximately 8 years after treatment of their brain metastasis, which was felt to be due to their previous brain irradiation. Here we discuss the treatment of solitary brain metastasis, particularly the value of combined method approaches in selected patients and dose-volume considerations

Effect of Tumor Subtype on Survival and the Graded Prognostic Assessment for Patients With Breast Cancer and Brain Metastases

Energy Technology Data Exchange (ETDEWEB)

Sperduto, Paul W., E-mail: psperduto@mropa.com [University of Minnesota Gamma Knife, Minneapolis Radiation Oncology, Minneapolis, MN (United States); Kased, Norbert [Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA (United States); Roberge, David [Radiation Oncology, McGill University Health Center, Montreal, QC (Canada); Xu Zhiyuan [Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Shanley, Ryan [Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Luo, Xianghua [Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN (United States); Sneed, Penny K. [Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA (United States); Chao, Samuel T. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Weil, Robert J. [Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Suh, John [Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Bhatt, Amit [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Jensen, Ashley W.; Brown, Paul D. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Shih, Helen A. [Massachusetts General Hospital, Department of Radiation Oncology, Harvard Medical School, Boston, MA (United States); Kirkpatrick, John [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Gaspar, Laurie E. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO (United States); Fiveash, John B. [Radiation Oncology, University of Alabama Medical Center at Birmingham, Birmingham, AL (United States); and others

2012-04-01

Purpose: The diagnosis-specific Graded Prognostic Assessment (GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast-GPA by analyzing a larger cohort and tumor subtype. Methods and Materials: A multi-institutional retrospective database of 400 breast cancer patients treated for newly diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression and recursive partitioning analysis (RPA). Factors were weighted by the magnitude of their regression coefficients to define the GPA index. Results: Significant prognostic factors by multivariate Cox regression and RPA were Karnofsky performance status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60 to 80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 3.4 (n = 23), 7.7 (n = 104), 15.1 (n = 140), and 25.3 (n = 133) months, respectively (p < 0.0001). Among HER2-negative patients, being ER/PR positive improved MST from 6.4 to 9.7 months, whereas in HER2-positive patients, being ER/PR positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA vs. 55 for tumor subtype. Conclusions: The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision making and stratification in clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone.

Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer: A retrospective study.

Science.gov (United States)

Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

2018-04-01

This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population.A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study.The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study.This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population.

Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

Energy Technology Data Exchange (ETDEWEB)

Koo, Tae Ryool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

2016-03-15

Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

Lung cancer brain metastases – the role of neurosurgery

Directory of Open Access Journals (Sweden)

V. A. Aleshin

2016-01-01

Full Text Available Lung cancer is mostly common occurring oncological disease in the developed countries. Currently lung cancers are subdivided into nonsmall-cell (adenocarcinoma, large-cell, squamous cell and small-cell. The difference in the clinical and morphological picture leads to the necessity of choosing therapeutic approaches to patients of various groups.Lung cancer should be referred to encephalotropic diseases since metastatic lesion of the central nervous system is sufficiently common complication. Successes of complex treatment of primary tumor result in increase of total longlivety currently ther is ageing of patients suffering lung cancer. These factors increase the risk of metastatic lesions of the brain.Interest to the problem of neurosurgical treatment of patients suffering lung cancer is determined by frequency of lesion, varicosity of morphological variants of the disease, requiring various algorithms of treatment and diagnosis.The main role of neurosurgical intervention in cerebral metastases of lung cancer consist in creation of the paled of carrying out combined therapy. Ideally, a neurosurgical operation should be carried out with clearcut observance of oncological principles of ablasty.Adequate comprehensive approach to treatment or patients with cerebral metastases of various forms of lung cancer with the developed of optimal tactics of and stages of treatment would make it possible to increase duration and quality of life of patients.

Icotinib as initial treatment in lung adenocarcinoma patients with brain metastases.

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Xu, Jian-Ping; Liu, Xiao-Yan; Yang, Sheng; Zhang, Chang-Gong; Wang, Lin; Shi, Yuan-Kai

2016-07-01

To evaluate the antitumor activity and toxicity of icotinib as initial treatment in lung adenocarcinoma patients with brain metastases. Twenty-one patients with histologically or pathologically documented brain metastatic lung cancer were administered icotinib as initial treatment from 2011 to 2015 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Chemotherapy response was assessed by Response Evaluation Criteria in Solid Tumors and toxicity was evaluated according to National Cancer Institute-Common Toxicity Criteria. Icotinib was administered three times per day at a dose of 125mg. The median overall and progression-free survival rates were 15.2 (1.2-31.5 months, 95% confidence interval [CI] 6.6-23.7 months) and 8.9 months (0.6-30.5 months, 95% CI 3.4-14.3 months), respectively. The overall response and disease control rates were 61.9% and 90.5%, respectively. Icotinib was well tolerated, and no grade 3/4 adverse events were observed. The most common grade 1/2 adverse events included acneiform eruptions (38.1%), diarrhea (19.0%), and stomatitis (9.5%). Icotinib is effective and well tolerated as initial treatment in lung adenocarcinoma patients with brain metastases.

Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.

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Patrick N Harter

Full Text Available The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to netrin-1 expression. Therefore, the aim of our study was to elucidate the association of netrin-1 expression and patient survival in brain metastases since those constitute one of the most limiting factors for patient prognosis. We investigated 104 brain metastases cases for netrin-1 expression using in-situ hybridization and immunohistochemistry with regard to clinical parameters such as patient survival and MRI data. Our data show that netrin-1 is strongly upregulated in most cancer subtypes. Univariate analyses revealed netrin-1 expression as a significant factor associated with poor patient survival in the total cohort of brain metastasis patients and in sub-entities such as non-small cell lung carcinomas. Interestingly, many cancer samples showed a strong nuclear netrin-1 signal which was recently linked to a truncated netrin-1 variant that enhances tumor growth. Nuclear netrin-1 expression was associated with poor patient survival in univariate as well as in multivariate analyses. Our data indicate both total and nuclear netrin-1 expression as prognostic factors in brain metastases patients in contrast to other prognostic markers in oncology such as patient age, number of brain metastases or Ki67 proliferation index. Therefore, nuclear netrin-1 expression constitutes one of the first reported molecular biomarkers for patient survival in brain metastases. Furthermore, netrin-1 may constitute a promising target for future anti-cancer treatment approaches in brain metastases.

Cerebellar metastases in patients with uterine cervical cancer. Two cases reports and review of the literature

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El Omari-Alaoui, H.; Gaye, P.M.; Kebdani, T.; El Ghazi, E.; Benjaafar, N.; Mansouri, A.; Errihani, H.; Kettani, F.; El Ouahabi, A.; El Gueddari, B.K.

2003-01-01

Brain metastases from cervical cancer are extremely rare. We report on two patients who developed cerebellar metastases following uterine cervical cancer. The interval between diagnosis of the primary cancer and diagnosis of brain metastasis was 8 months. The main complaint was symptoms of increased intracranial pressure and cerebellar syndrome. Surgical excision of the brain lesion followed by radiation therapy was performed in the first case. The second patient received palliative radiation therapy. The first patient died 8 months after diagnosis. The second patient is alive 2 months after diagnosis. (authors)

EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer: a pooled analysis of published data

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Fan Y

2014-11-01

Full Text Available Yun Fan,1,2 Xiaoling Xu,3 Conghua Xie4 1Zhongnan Hospital of Wuhan University, Department of Radiation Oncology, Wuhan, People's Republic of China; 2Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 3Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 4Zhongnan Hospital of Wuhan University, Department of Radiation Oncology, Wuhan, People’s Republic of China Introduction: Brain metastases are one of the leading causes of death from non-small-cell lung cancer (NSCLC. The use of epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs to treat brain metastases remains controversial. Thus, we performed a pooled analysis of published data to evaluate the efficacy of EGFR-TKIs in NSCLC patients with brain metastases, particularly for tumors with activating EGFR mutations. Methods: Several data sources were searched, including PubMed, Web of Science, and ASCO Annual Meetings databases. The end points were intracranial overall response rate (ORR, disease control rate (DCR, progression-free survival (PFS, overall survival (OS, and adverse events. The pooled ORR, DCR, PFS, and OS with 95% confidence intervals (CIs were calculated employing fixed- or random-effect models, depending on the heterogeneity of the included studies. Results: Sixteen published studies were included in this analysis, with a total of 464 enrolled patients. The EGFR mutational status was unknown for 362 (unselected group, and 102 had activating EGFR mutations. The pooled intracranial ORR and DCR were 51.8% (95% CI: 45.8%–57.8% and 75.7% (95% CI: 70.3%–80.5%, respectively. A higher ORR was observed in the EGFR mutation group than in the unselected group (85.0% vs 45.1%; a similar trend was observed for the DCR (94.6% vs 71.3%. The pooled median PFS and OS were 7.4 months (95% CI, 4.9–9.9 and 11.9 months (95% CI, 7.7–16.2, respectively, with longer PFS (12.3 months vs 5.9 months and OS (16.2 months vs

Radiation dose and cancer risk among pediatric patients undergoing interventional neuroradiology procedures

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Thierry-Chef, Isabelle; Simon, Steven L.; Miller, Donald L.

2006-01-01

During interventional neuroradiology procedures, patients can be exposed to moderate to high levels of radiation. Special considerations are required to protect children, who are generally more sensitive to the short- and long-term detrimental effects of radiation exposure. Estimates of dose to the skin of children from certain interventional procedures have been published elsewhere, but we are not aware of data on dose to the brain or on the long-term risk of cancer from brain radiation. Our goals were to estimate radiation doses to the brain in 50 pediatric patients who had undergone cerebral embolization and to assess their lifetime risks of developing radiation-related brain cancer. Entrance-peak skin dose and various assumptions on conditions of exposure were used as input for dosimetric calculations to estimate the spatial pattern of dose within the brain and the average dose to the whole brain for each child. The average dose and the age of the child at time of exposure were used to estimate the lifetime risk of developing radiation-related brain cancer. Among the 50 patients, average radiation doses to the brain were estimated to vary from 100 mGy to 1,300 mGy if exposed to non-collimated fields and from 20 mGy to 160 mGy for collimated, moving fields. The lifetime risk of developing brain cancer was estimated to be increased by 2% to 80% as a result of the exposure. Given the very small lifetime background risk of brain tumor, the excess number of cases will be small even though the relative increase might be as high as 80%. ALARA principles of collimation and dose optimization are the most effective means to minimize the risk of future radiation-related cancer. (orig.)

Comparison of cerebral metabolism of glucose in normal human and cancer patients

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Si, M.

2007-01-01

Full text: Objective: To determine whether the cerebral metabolism in various regions of the normal human brain differs from those of cancer patients in aging by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples so called 'normal group' (ranging 21 to 88; mean age+/-SD: 50+/-14) and 290 cancer patients called 'cancer group' (ranging 21 to 85; mean age+/-SD: 54+/-14) who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They were selected with: (i) absence of clear focal brain lesions (epilepsy, cerebrovascular diseases etc.); (ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes; (iii) absence of psychiatric disorders and abuse of drugs and alcohol;( iiii) cancer patients were diagnosed definitely of variable cancers except brain cancer or brain metastasis. Both groups were sub grouped into six with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose are matched. All 12 subgroups were compared to the subgroup of normal 31-40 years old called 'control subgroup' (84 samples; mean age+/-SD: 37.15+/- 2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later; their brains were scanned for 10 minutes. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2). The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three dimensional localized by MNI Space utility (MSU) software. Results:1.With increasing of age interval, similar hypometabolic brain areas are detected in both 'normal group' and 'cancer group', they are mainly in the cortical structures such as bilateral prefrontal cortex (BA9), superior temporal gyrus (BA22), parietal cortex (inferior parietal lobule and precuneus(BA40), insula (BA13

Causes of death among cancer patients.

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Zaorsky, N G; Churilla, T M; Egleston, B L; Fisher, S G; Ridge, J A; Horwitz, E M; Meyer, J E

2017-02-01

The purpose of our study was to characterize the causes of death among cancer patients as a function of objectives: (i) calendar year, (ii) patient age, and (iii) time after diagnosis. US death certificate data in Surveillance, Epidemiology, and End Results Stat 8.2.1 were used to categorize cancer patient death as being due to index-cancer, nonindex-cancer, and noncancer cause from 1973 to 2012. In addition, data were characterized with standardized mortality ratios (SMRs), which provide the relative risk of death compared with all persons. The greatest relative decrease in index-cancer death (generally from > 60% to deaths were stable (typically >40%) among patients with cancers of the liver, pancreas, esophagus, and lung, and brain. Noncancer causes of death were highest in patients with cancers of the colorectum, bladder, kidney, endometrium, breast, prostate, testis; >40% of deaths from heart disease. The highest SMRs were from nonbacterial infections, particularly among 1,000 for lymphomas, P death from index- and nonindex-cancers varies widely among primary sites. Risk of noncancer deaths now surpasses that of cancer deaths, particularly for young patients in the year after diagnosis. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The role of chemotherapy in the treatment of patients with brain metastases from solid tumors

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Walbert, T.; Gilbert, M.R.

2009-01-01

Brain metastases are the most frequent cancer in the central nervous system, being ten times more common than primary brain tumors. Patients generally have a poor outcome with a median survival of 4 months after diagnosis of the metastases. Therapeutic options include surgery, stereotactic, radiosurgery, whole-brain radiotherapy (WBRT), and chemotherapy. Patients with a limited number of brain metastases and well-controlled systemic cancer benefit from brain metastases-specific therapies, including surgery, radiosurgery, and conventional radiation. The role of chemotherapy for brain metastases remains limited. There is concern about drug delivery because of the blood-brain barrier. However, higher response rates are noted with initial therapies, suggesting that part of the poor response rate may be related to the late onset of brain metastases and the use of second- and third-line regimens. Recent studies have demonstrated objective responses with systemic therapy in a variety of cancer types, especially when combined with WBRT. Individual therapeutic strategies for central nervous system metastases must be chosen based on performance status, the extent of intracranial disease, and the chemosensitivity of the underlying tumor, as well as the control of the systemic cancer. In this article we review important prognostic factors and challenges in using chemotherapy. We specifically review recent advances in the treatment of brain metastases from breast and lung cancer as well as melanoma. Future treatment advances will require a multidisciplinary approach integrating surgical, radiation, and chemotherapeutic options to improve neurological function and quality of life, rather than just focusing on survival endpoints. (author)

Self-Reported Cognitive Outcomes in Patients With Brain Metastases Before and After Radiation Therapy

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Cole, Ansa Maer [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany); Scherwath, Angela [Department of Medical Psychology, University Medical Centre Hamburg-Eppendorf, Hamburg (Germany); Ernst, Gundula [Department of Medical Psychology, Medical School Hannover, Hannover (Germany); Lanfermann, Heinrich [Institute for Neuroradiology, Medical School Hannover, Hannover (Germany); Bremer, Michael [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany); Steinmann, Diana, E-mail: steinmann.diana@mh-hannover.de [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany)

2013-11-15

Purpose: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. Methods and Materials: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). Results: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. Conclusion: Self-reported attention declined in

Self-Reported Cognitive Outcomes in Patients With Brain Metastases Before and After Radiation Therapy

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Cole, Ansa Maer; Scherwath, Angela; Ernst, Gundula; Lanfermann, Heinrich; Bremer, Michael; Steinmann, Diana

2013-01-01

Purpose: Patients with brain metastases may experience treatment-related cognitive deficits. In this study, we prospectively assessed the self-reported cognitive abilities of patients with brain metastases from any solid primary cancer before and after irradiation of the brain. Methods and Materials: The treatment group (TG) consisted of adult patients (n=50) with brain metastases who received whole or partial irradiation of the brain without having received prior radiation therapy (RT). The control group (CG) consisted of breast cancer patients (n=27) without cranial involvement who were treated with adjuvant RT. Patients were recruited between May 2008 and December 2010. Self-reported cognitive abilities were acquired before RT and 6 weeks, 3 months, and 6 months after irradiation. The information regarding the neurocognitive status was collected by use of the German questionnaires for self-perceived deficits in attention (FEDA) and subjectively experienced everyday memory performance (FEAG). Results: The baseline data showed a high proportion of self-perceived neurocognitive deficits in both groups. A comparison between the TG and the CG regarding the course of self-reported outcomes after RT showed significant between-group differences for the FEDA scales 2 and 3: fatigue and retardation of daily living activities (P=.002) and decrease in motivation (P=.032) with an increase of attention deficits in the TG, but not in the CG. There was a trend towards significance in FEDA scale 1: distractibility and retardation of mental processes (P=.059) between the TG and the CG. The FEAG assessment presented no significant differences. An additional subgroup analysis within the TG was carried out. FEDA scale 3 showed significant differences in the time-related progress between patients with whole-brain RT and those receiving hypofractionated stereotactic RT (P=.025), with less decrease in motivation in the latter group. Conclusion: Self-reported attention declined in

Subjective cognitive impairment and brain structural networks in Chinese gynaecological cancer survivors compared with age-matched controls: a cross-sectional study.

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Zeng, Yingchun; Cheng, Andy S K; Song, Ting; Sheng, Xiujie; Zhang, Yang; Liu, Xiangyu; Chan, Chetwyn C H

2017-11-28

Subjective cognitive impairment can be a significant and prevalent problem for gynaecological cancer survivors. The aims of this study were to assess subjective cognitive functioning in gynaecological cancer survivors after primary cancer treatment, and to investigate the impact of cancer treatment on brain structural networks and its association with subjective cognitive impairment. This was a cross-sectional survey using a self-reported questionnaire by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) to assess subjective cognitive functioning, and applying DTI (diffusion tensor imaging) and graph theoretical analyses to investigate brain structural networks after primary cancer treatment. A total of 158 patients with gynaecological cancer (mean age, 45.86 years) and 130 age-matched non-cancer controls (mean age, 44.55 years) were assessed. Patients reported significantly greater subjective cognitive functioning on the FACT-Cog total score and two subscales of perceived cognitive impairment and perceived cognitive ability (all p values impairment (r = -0.388, p = 0.034). When compared with non-cancer controls, a considerable proportion of gynaecological cancer survivors may exhibit subjective cognitive impairment. This study provides the first evidence of brain structural network alteration in gynaecological cancer patients at post-treatment, and offers novel insights regarding the possible neurobiological mechanism of cancer-related cognitive impairment (CRCI) in gynaecological cancer patients. As primary cancer treatment can result in a more random organisation of structural brain networks, this may reduce brain functional specificity and segregation, and have implications for cognitive impairment. Future prospective and longitudinal studies are needed to build upon the study findings in order to assess potentially relevant clinical and psychosocial variables and brain network measures, so as to more accurately understand the

Neuro emotional technique effects on brain physiology in cancer patients with traumatic stress symptoms: preliminary findings.

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Monti, Daniel A; Tobia, Anna; Stoner, Marie; Wintering, Nancy; Matthews, Michael; He, Xiao-Song; Doucet, Gaelle; Chervoneva, Inna; Tracy, Joseph I; Newberg, Andrew B

2017-08-01

The purpose of this study was to characterize the neurophysiological and clinical effects that may result from the neuro emotional technique (NET) in patients with traumatic stress symptoms associated with a cancer-related event. We hypothesized that self-regulatory processing of traumatic memories would be observable as physiological changes in key brain areas after undergoing the NET intervention and that these changes would be associated with improvement of traumatic stress symptoms. We enrolled 23 participants with a prior cancer diagnosis who expressed a distressing cancer-related memory that was associated with traumatic stress symptoms of at least 6 months in duration. Participants were randomized to either the NET intervention or a waitlist control condition. To evaluate the primary outcome of neurophysiological effects, all participants received functional magnetic resonance imaging (fMRI) during the auditory presentation of both a neutral stimulus and a description of the specific traumatic event. Pre/post-comparisons were performed between the traumatic and neutral condition, within and between groups. Psychological measures included the Impact of Event Scale (IES), State Trait Anxiety Index (STAI), Brief Symptom Inventory (BSI)-18, and Posttraumatic Cognitions Inventory (PTCI). The initial fMRI scans in both groups showed significant increases in the bilateral parahippocampus and brainstem. After NET, reactivity in the parahippocampus, brainstem, anterior cingulate, and insula was significantly decreased during the traumatic stimulus. Likewise, participants receiving the NET intervention had significant reductions (p stress as measured by the IES and PTCI. This study is an initial step towards understanding mechanistic features of the NET intervention. Specifically, brain regions involved with traumatic memories and distress such as the brainstem, insula, anterior cingulate gyrus, and parahippocampus had significantly reduced activity after the NET

SU-E-J-90: MRI-Based Treatment Simulation and Patient Setup for Radiation Therapy of Brain Cancer

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Yang, Y [UCLA School of Medicine, Los Angeles, AA (United States); Cao, M; Han, F; Santhanam, A; Neylon, J; Gomez, C; Kaprealian, T; Sheng, K; Agazaryan, N; Low, D; Hu, P

2014-06-01

Purpose: Traditional radiation therapy of cancer is heavily dependent on CT. CT provides excellent depiction of the bones but lacks good soft tissue contrast, which makes contouring difficult. Often, MRIs are fused with CT to take advantage of its superior soft tissue contrast. Such an approach has drawbacks. It is desirable to perform treatment simulation entirely based on MRI. To achieve MR-based simulation for radiation therapy, bone imaging is an important challenge because of the low MR signal intensity from bone due to its ultra-short T2 and T1, which presents difficulty for both dose calculation and patient setup in terms of digitally reconstructed radiograph (DRR) generation. Current solutions will either require manual bone contouring or multiple MR scans. We present a technique to generate DRR using MRI with an Ultra Short Echo Time (UTE) sequence which is applicable to both OBI and ExacTrac 2D patient setup. Methods: Seven brain cancer patients were scanned at 1.5 Tesla using a radial UTE sequence. The sequence acquires two images at two different echo times. The two images were processed using in-house software. The resultant bone images were subsequently loaded into commercial systems to generate DRRs. Simulation and patient clinical on-board images were used to evaluate 2D patient setup with MRI-DRRs. Results: The majority bones are well visualized in all patients. The fused image of patient CT with the MR bone image demonstrates the accuracy of automatic bone identification using our technique. The generated DRR is of good quality. Accuracy of 2D patient setup by using MRI-DRR is comparable to CT-based 2D patient setup. Conclusion: This study shows the potential of DRR generation with single MR sequence. Further work will be needed on MR sequence development and post-processing procedure to achieve robust MR bone imaging for other human sites in addition to brain.

Use of bone and brain scans as screening procedures in patients with malignant lesions

International Nuclear Information System (INIS)

Felix, E.L.; Sindelar, W.F.; Bagley, D.H.; Johnston, G.S.; Ketcham, A.S.

1975-01-01

A retrospective study to determine the value of bone and brain scans was performed in preoperative patients with melanoma, sarcoma, cancer of the head and neck and carcinoma of the pelvis. No occult metastases were identified in 170 patients in whom brain scan was performed. On late follow-up data, eight patients had neurologic symptoms develop and had brain metastases identified on scan. Of 223 bone scans performed, only one distant metastatic lesion was identified. It is, therefore, suggested that, in these types of patients, bone and brain scans be reserved for those with symptoms referable to the neurologic or skeletal systems

Gamma-knife radiosurgery for metastatic brain tumors from primary lung cancer

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Uchiyama, Bine; Satoh, Ken; Saijo, Yasuo

1998-01-01

Forty patients with metastatic brain tumors from primary lung cancer underwent radiosurgery (γ-knife). We retrospectively compared their prior treatment history, number of metastatic foci, and performance status, to evaluate the effects of, and indications for, γ-knife therapy. After both the primary and the metastatic tumors were controlled, performance status could be used as an index in the choice of γ-knife therapy. Our results demonstrate that repeated γ-knife radiosurgeries prolonged survival time. Gamma-knife radiosurgery improves quality of life and prognosis of patients with metastatic brain tumors. (author)

A case of leukoencephalopathy caused by radiation and chemotherapy for brain metastasis of breast cancer

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Yamamoto, Shigeru; Sonoo, Hiroshi; Nomura, Tsunehisa; Ohkubo, Sumiko; Yamamoto, Yutaka; Tanaka, Katsuhiro; Kurebayashi, Junichi; Hiratsuka, Junichi [Kawasaki Medical School, Kurashiki, Okayama (Japan)

2002-08-01

A case of treatment-related leukoencephalopathy is presented. A patient with breast cancer metastasis to the brain, liver, bone and distant lymph nodes was treated with whole brain radiation and docetaxcel. Eleven months after radiation, magnetic resonance imaging showed diffuse leukoencephalopathy. Twenty-two months after radiation, the patient had gait disturbance, parkinsonism, dementia and urinary incontinence. From this experience, stereotactic radiosurgery such as cyber knife and gamma knife therapy, representing a new modality for delivering intense focal radiation, should be come preferred techniques for treating patients with brain metastases, to avoid the potential cognitive side effects of fractionated whole-brain radiotherapy. (author)

Neurocognitive function, brain-derived neurotrophic factor (BDNF) and IL-6 levels in cancer patients with depression.

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Jehn, C F; Becker, B; Flath, B; Nogai, H; Vuong, L; Schmid, P; Lüftner, D

2015-10-15

Increased IL-6 and decreased brain-derived neurotrophic factor (BDNF) levels have been implicated in the pathophysiology of depression. The objective was to assess the influence of BDNF and IL-6 on cognitive function and depression in patients with cancer. Serum BDNF and plasma IL-6 were measured in patients with metastatic cancer. Diagnosis of depression was established according to DSM-IV criteria. Cognitive function was assessed by the Verbal Learning and Memory Test (VLMT). A total of 59 patients were recruited in this study. Only IL-6 levels were significantly elevated in patients with clinical depression (35.7 vs. 6.9 pg/ml; pBDNF levels (p=0.16). Patients with clinical depression showed significant impairment of short-term memory (STM) (24.4 vs. 37.5; p=0.01), but not of long-term memory (LTM) (3.9 vs. 2.8; p=0.3). STM was dependent on the level of BDNF and younger age (b=0.60; p=0.001; b= -0.63; p=0.003, respectively). IL-6 was not only strongly associated with depression, but was an independent predictor of BDNF level as well (b= -0.50; p=0.01). LTM was associated only with a good KPS (b=0.47; p=0.037). Hemoglobin levels and the prior number of chemotherapy lines were not predictive of memory performance. Low BDNF is associated with cognitive impairment, STM, in patients with cancer, however no influence on depression could be found. IL-6 is strongly associated with depression and an independent predictor of BDNF levels. Copyright © 2015 Elsevier B.V. All rights reserved.

Uterine cervical cancer with brain metastasis as the initial site of presentation.

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Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

2015-07-01

Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets.

Science.gov (United States)

Seyfried, Thomas N; Kiebish, Michael; Mukherjee, Purna; Marsh, Jeremy

2008-11-01

Information is presented on the calorically restricted ketogenic diet (CRKD) as an alternative therapy for brain cancer. In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic due to mitochondrial defects and have a reduced ability to metabolize ketone bodies. The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms.

Incidence, symptoms, treatment, and prognosis in 113 patients with brain/meningeal metastasis from breast cancer. Screening in accordance with hormone receptor and HER2/neu

International Nuclear Information System (INIS)

Kan, Norimichi; Takada, Masayasu; Kuwata, Katsuya

2009-01-01

In 113 of 422 patients with metastatic/recurrent breast cancer (MBC who were treated in our hospital after 2001, brain/meningeal metastasis was detected. In 240 patients who died, the overall incidence of brain/meningeal metastasis was 36.3% (n=87). With respect to hormone receptor (HR) and HER2 presence, metastasis was detected in 32 (58.2%) of 55 patients showing HR(-) and HER2(+), 17 (39.5%) of 43 patients showing HR(-) and HER2(-), 19 (31.5%) of 54 patients showing HR(+) and HER2(+), and 17 (20%) of 85 patients showing HR(+) and HER2(-) (brain metastasis was detected in 2 of 3 patients in whom HR or HER2 was unclear); the incidence was significantly higher in HR(-) or HER2(+) patients. Of our series including surviving patients, asymptomatic brain metastasis was detected using contrast-enhanced MRI in 24 HER2(+) patients. In the above 113 patients, the median survival time (MST) after diagnosis was 10 months. However, it was 17 months in 24 patients who underwent screening. For treatment, whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) mainly with a gamma knife was performed. During a follow-up of more than 12 months, 1 to 4 sessions of treatment (mean: 2.39, median: 2) were required. In 50% of the patients, both WBRT and SRS were performed. There were no HR- or HER2- related differences in survival after brain metastasis. However, the MST was 34 months in 7 patients in whom the 1st relapse site involved the brain. In the future, the usefulness of early treatment via brain metastasis screening should be reviewed in HR(-) and HER2(+) patients. (author)

Phase I Study of Concurrent Whole Brain Radiotherapy and Erlotinib for Multiple Brain Metastases From Non-Small-Cell Lung Cancer

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Lind, Joline S.W.; Lagerwaard, Frank J.; Smit, Egbert F.; Senan, Suresh

2009-01-01

Purpose: Erlotinib has shown activity in patients with brain metastases from non-small-cell lung cancer. The present dose-escalation Phase I trial evaluated the toxicity of whole brain radiotherapy (WBRT) with concurrent and maintenance erlotinib in this patient group. Methods and Materials: Erlotinib (Cohort 1, 100 mg/d; Cohort 2, 150 mg/d) was started 1 week before, and continued during, WBRT (30 Gy in 10 fractions). Maintenance erlotinib (150 mg/d) was continued until unacceptable toxicity or disease progression. Results: A total of 11 patients completed WBRT, 4 in Cohort 1 and 7 in Cohort 2. The median duration of erlotinib treatment was 83 days. No treatment-related neurotoxicity was observed. No treatment-related Grade 3 or greater toxicity occurred in Cohort 1. In Cohort 2, 1 patient developed a Grade 3 acneiform rash and 1 patient had Grade 3 fatigue. Two patients in Cohort 2 developed erlotinib-related interstitial lung disease, contributing to death during maintenance therapy. The median overall survival and interval to progression was 133 and 141 days, respectively. Six patients developed extracranial progression; only 1 patient had intracranial progression. In 7 patients with follow-up neuroimaging at 3 months, 5 had a partial response and 2 had stable disease. Conclusion: WBRT with concurrent erlotinib is well tolerated in patients with brain metastases from non-small-cell lung cancer. The suggestion of a high intracranial disease control rate warrants additional study.

Evaluation of Biomarkers Predictive of Benefit from the PD-1 Inhibitor MK-3475 in Patients with Non-Small Cell Lung Cancer and Brain Metastases

Science.gov (United States)

2017-07-01

Small Cell Lung Cancer and Brain Metastases PRINCIPAL INVESTIGATOR: Sarah B. Goldberg, MD CONTRACTING ORGANIZATION: Yale University New Haven, CT...benefit in patients with non- small cell lung cancer (NSCLC). However, the overall response rate is only 20-30% and there is no clearly-defined...9. Appendices……………………………………………………………14 4 1. INTRODUCTION: Lung cancer is the leading cause of cancer death in the United States, resulting in more

Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small-cell lung cancer: A Cochrane Review

International Nuclear Information System (INIS)

Lester, Jason Francis; MacBeth, Fergus R.; Coles, Bernadette

2005-01-01

Purpose: To investigate whether prophylactic cranial irradiation (PCI) has a role in the management of patients with non-small-cell lung cancer (NSCLC) treated with curative intent. Methods and Materials: A search strategy was designed to identify randomized controlled trials (RCTs) comparing PCI with no PCI in NSCLC patients treated with curative intent. The electronic databases MEDLINE, EMBASE, LILACS, and Cancerlit were searched, along with relevant journals, books, and review articles to identify potentially eligible trials. Four RCTs were identified and reviewed. A total of 951 patients were randomized in these RCTs, of whom 833 were evaluable and reported. Forty-two patients with small-cell lung cancer were excluded, leaving 791 patients in total. Because of the small patient numbers and trial heterogeneity, no meta-analysis was attempted. Results: Prophylactic cranial irradiation did significantly reduce the incidence of brain metastases in three trials. No trial reported a survival advantage with PCI over observation. Toxicity data were poorly collected and no quality of life assessments were carried out in any trial. Conclusion: Prophylactic cranial irradiation may reduce the incidence of brain metastases, but there is no evidence of a survival benefit. It was not possible to evaluate whether any radiotherapy regimen is superior, and the effect of PCI on quality of life is not known. There is insufficient evidence to support the use of PCI in clinical practice. Where possible, patients should be offered entry into a clinical trial

Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.

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Cortés, Javier; Rugo, Hope S; Awada, Ahmad; Twelves, Chris; Perez, Edith A; Im, Seock-Ah; Gómez-Pardo, Patricia; Schwartzberg, Lee S; Diéras, Veronique; Yardley, Denise A; Potter, David A; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol; Hoch, Ute; Tagliaferri, Mary; Hannah, Alison L; O'Shaughnessy, Joyce

2017-09-01

Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician's choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744).

Greater efficacy of chemotherapy plus bevacizumab compared to chemo- and targeted therapy alone on non-small cell lung cancer patients with brain metastasis.

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Tang, Ning; Guo, Jun; Zhang, Qianqian; Wang, Yali; Wang, Zhehai

2016-01-19

Control of non-small-cell lung cancer (NSCLC) with brain metastasis is clinically challenging. This study retrospectively evaluated the efficacy of different adjuvant therapies for 776 cases of advanced NSCLCs with brain metastasis who treated with chemotherapy, chemotherapy plus bevacizumab, tyrosine kinase inhibitor (TKI) alone, or supportive care. The median progression-free survival (mPFS) and median overall survival (mOS) of patients treated with chemotherapy plus bevacizumab were 8.5 and 10.5 months, respectively, which were better than those of patients treated with other three therapies(P chemotherapy plus bevacizumab but was significantly better than that of other therapies. Moreover, for patients with EGFR wild-type NSCLC, the mPFS and mOS after chemotherapy plus bevacizumab were greater than those with other two therapies (P Chemotherapy plus bevacizumab was more effective for NSCLC patients with brain metastasis. Further studies will investigate the benefit of TKI alone for patients with EGFR-mutated. For patients with EGFR wild-type, chemotherapy plus bevacizumab did improve PFS and OS. Furthermore, regimens including pemetrexed led to a greater RR.

Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline.

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Ramakrishna, Naren; Temin, Sarah; Chandarlapaty, Sarat; Crews, Jennie R; Davidson, Nancy E; Esteva, Francisco J; Giordano, Sharon H; Gonzalez-Angulo, Ana M; Kirshner, Jeffrey J; Krop, Ian; Levinson, Jennifer; Modi, Shanu; Patt, Debra A; Perez, Edith A; Perlmutter, Jane; Winer, Eric P; Lin, Nancy U

2014-07-01

To provide formal expert consensus-based recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer. The American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus-based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations. No studies or existing guidelines met the systematic review criteria; therefore, ASCO conducted a formal expert consensus-based process. Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. Clinicians should not perform routine magnetic resonance imaging (MRI) to screen for brain metastases, but rather should have a low threshold for MRI of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer. © 2014 by American Society of Clinical Oncology.

Stacking denoising auto-encoders in a deep network to segment the brainstem on MRI in brain cancer patients: A clinical study.

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Dolz, Jose; Betrouni, Nacim; Quidet, Mathilde; Kharroubi, Dris; Leroy, Henri A; Reyns, Nicolas; Massoptier, Laurent; Vermandel, Maximilien

2016-09-01

Delineation of organs at risk (OARs) is a crucial step in surgical and treatment planning in brain cancer, where precise OARs volume delineation is required. However, this task is still often manually performed, which is time-consuming and prone to observer variability. To tackle these issues a deep learning approach based on stacking denoising auto-encoders has been proposed to segment the brainstem on magnetic resonance images in brain cancer context. Additionally to classical features used in machine learning to segment brain structures, two new features are suggested. Four experts participated in this study by segmenting the brainstem on 9 patients who underwent radiosurgery. Analysis of variance on shape and volume similarity metrics indicated that there were significant differences (p<0.05) between the groups of manual annotations and automatic segmentations. Experimental evaluation also showed an overlapping higher than 90% with respect to the ground truth. These results are comparable, and often higher, to those of the state of the art segmentation methods but with a considerably reduction of the segmentation time. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

International Nuclear Information System (INIS)

Gorovets, Daniel; Ayala-Peacock, Diandra; Tybor, David J.; Rava, Paul; Ebner, Daniel; Cielo, Deus; Norén, Georg; Wazer, David E.; Chan, Michael; Hepel, Jaroslaw T.

2017-01-01

Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

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Gorovets, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, Perlmutter Cancer Center, NYU School of Medicine, New York, New York (United States); Ayala-Peacock, Diandra [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Tybor, David J. [Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts (United States); Rava, Paul [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, UMass Memorial Medical Center, University of Massachusetts School of Medicine, Worcester, Massachusetts (United States); Ebner, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Cielo, Deus; Norén, Georg [Department of Neurosurgery, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Wazer, David E. [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Chan, Michael [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States)

2017-02-01

Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

The validation of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30 in pre-operative patients with brain tumor in China

Directory of Open Access Journals (Sweden)

Zhang Hong-ying

2011-04-01

Full Text Available Abstract Background Health related quality of life (HRQOL has increasingly emphasized on cancer patients. The psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0 in brain tumor patients wasn't proven, and there was no baseline HRQOL in brain tumor patients prior to surgery. Methods The questionnaire EORTC QLQ-C30 (version 3.0 was administered at three time points: T1, the first or the second day that patients were hospitalized after the brain tumor suspected or diagnosed by MRI or CT; T2, 1 to 2 days after T1, (T1 and T2 were both before surgery; T3, the day before discharge. Clinical variables included disease histologic types, cognitive function, and Karnofsky Performance Status. Results Cronbach's alpha coefficients for multi-item scales were greater than .70 and multitrait scaling analysis showed that most of the item-scale correlation coefficients met the standards of convergent and discriminant validity, except for the cognitive functioning scale. All scales and items exhibited construct validity. Score changes over peri-operation were observed in physical and role functioning scales. Compared with mixed cancer patients assessed after surgery but before adjuvant treatment, brain tumor patients assessed pre-surgery presented better function and fewer symptoms. Conclusions The standard Chinese version of the EORTC QLQ-C30 was overall a valid instrument to assess HRQOL in brain tumor patients in China. The baseline HRQOL in brain tumor patients pre-surgery was better than that in mixed cancer patients post-surgery. Future study should modify cognitive functioning scale and examine test-retest reliability and response validity.

Chemotherapy in the management of brain metastases: the emerging role of fotemustine for patients with melanoma and NSCLC.

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Addeo, Raffaele; Zappavigna, Silvia; Luce, Amalia; Facchini, Sergio; Caraglia, Michele

2013-09-01

An estimated 20 - 40% of cancer patients will develop brain metastases that are the most common intracranial tumors in adults. Patients with cerebral metastases represent a variegate group where selection of the most appropriate treatment depends on many patient- and disease-related factors. The impact of therapeutic option on overall survival is lacking and it is important to consider quality of life (QOL) when treating patients with brain metastases. A considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. The role of chemotherapy was limited in the past. Recently, several chemotherapeutic agents have been identified as potentially useful. This article examines the pharmacokinetics, efficacy and safety and tolerability of fotemustine (FTM) for the management of patients with cerebral metastasis from melanoma and non-small cell lung cancer (NSCLC). FTM is a third-generation nitrosourea that has proved its efficacy on brain metastases of melanoma and showed promising results for the treatment of brain metastasis of NSCLC because of its ability to pass the blood-brain barrier.

Gamma knife radiosurgery for metastatic brain tumors from lung cancer

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Serizawa, Toru; Ono, Junichi; Iuchi, Toshihiko [Chiba Cardiovascular Center, Ichihara (Japan). Chiba Cancer Center] (and others)

2003-01-01

The purpose of this retrospective study is to evaluate the effectiveness of gamma knife radiosurgery (GKS) alone for metastatic brain tumors from lung cancer. Two hundred thirty-one consecutive patients with metastatic brain tumors from lung cancer filling the following 4 criteria were analyzed for this study; no prior brain tumor treatment, 25 or fewer lesions, a maximum 5 tumors with diameter of 2 cm or more, no surgically inaccessible tumor 3 cm or greater in diameter. According to the same treatment protocol, large tumors ({>=} 3 cm) were surgically removed and all the other small lesions (<3 cm) were treated with GKS. New lesions were treated with repeated GKS. The tumor-progression-free, overall, neurological, lowered-QOL (quality of life)-free and new-lesion-free survivals were calculated with the Kaplan-Meier method. The poor prognostic factors for each survival were also analyzed with the Cox's proportional hazard model. The tumor control rate at 1 year was 96.5%. The estimated median overall survival time was 7.7 months. The first-year survival rates were 83.0% in neurological survival and 76.0% in lowered-QOL-free survival. The new-lesion-free survival at 1 year was 27.9%. Multivariate analysis revealed significant poor prognostic factors for neurological and lowered-QOL-free survivals were carcinomatous meningitis and >10 brain lesions. This study suggests the results of GKS for metastatic brain tumors from lung cancer are quite satisfactory considering prevention of neurological death and maintenance of QOL. But cases with carcinomatous meningitis and/or >10 brain lesions are not good candidates for GKS alone. (author)

Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial.

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Yang, Jin-Ji; Zhou, Caicun; Huang, Yisheng; Feng, Jifeng; Lu, Sun; Song, Yong; Huang, Cheng; Wu, Gang; Zhang, Li; Cheng, Ying; Hu, Chengping; Chen, Gongyan; Zhang, Li; Liu, Xiaoqing; Yan, Hong Hong; Tan, Fen Lai; Zhong, Wenzhao; Wu, Yi-Long

2017-09-01

For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China. Eligible participants were patients with NSCLC with EGFR mutations, who were naive to treatment with EGFR-TKIs or radiotherapy, and had at least three metastatic brain lesions. We randomly assigned participants (1:1) to either icotinib 125 mg orally (three times per day) or WBI (30 Gy in ten fractions of 3 Gy) plus concurrent or sequential chemotherapy for 4-6 cycles, until unacceptable adverse events or intracranial disease progression occurred. The randomisation was done by the Chinese Thoracic Oncology Group with a web-based allocation system applying the Pocock and Simon minimisation method; groups were stratified by EGFR gene mutation status, treatment line (first line or second line), brain metastases only versus both intracranial and extracranial metastases, and presence or absence of symptoms of intracranial hypertension. Clinicians and patients were not masked to treatment assignment, but individuals involved in the data analysis did not participate in the treatments and were thus masked to allocation. Patients receiving icotinib who had intracranial progression only were switched to WBI plus either icotinib or chemotherapy until further progression; those receiving icotinib who had extracranial progression only were switched to icotinib plus chemotherapy. Patients receiving WBI who progressed were switched to icotinib until further progression. Icotinib could be continued beyond progression if a clinical benefit

Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis.

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Saldana, Sandra M; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

2013-01-01

Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.

Computed tomography in brain metastases of colorectal cancer

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Kuratsu, Jun-ichi; Matsukado, Yasuhiko; Sueyoshi, Nobuyuki [Kumamoto Univ. (Japan). School of Medicine; Nonaka, Nobuhito; Sano, Yoshinori; Itoyama, Yoichi; Miura, Giichi

1984-10-01

Metastatic brain tumors from colorectal cancers are relatively rare. In previous reports, the incidence ranged from 3 to 5 percent of all metastatic brain tumors. We report 7 cases of metastatic brain tumors from colorectal cancers. The time interval from the diagnosis of the primary tumors to the brain metastasis was 3 years on the average. Metastasis to the lung and liver were also found in 6 cases at the time of the diagnosis of the brain metastasis. The CEA levels in the serum were highly elevated in all cases. Solitary metastasis was found in all cases; cancers tend to metastasize in the deep area of the cerebrum or cerebellum. On a plain CT scan, tumors were demonstrated as ring-type, with a high-density mass, and ring-like enhancement was seen in 6 cases. Prognosis was very poor in most cases. The median survival time from diagnosis of brain metastasis was 4.5 months in the 2 cases with surgery and 3.5 months in the 4 cases without surgery.

Brain Functional Connectivity in Small Cell Lung Cancer Population after Chemotherapy Treatment: an ICA fMRI Study

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Bromis, K.; Kakkos, I.; Gkiatis, K.; Karanasiou, I. S.; Matsopoulos, G. K.

2017-11-01

Previous neurocognitive assessments in Small Cell Lung Cancer (SCLC) population, highlight the presence of neurocognitive impairments (mainly in attention processing and executive functioning) in this type of cancer. The majority of these studies, associate these deficits with the Prophylactic Cranial Irradiation (PCI) that patients undergo in order to avoid brain metastasis. However, there is not much evidence exploring cognitive impairments induced by chemotherapy in SCLC patients. For this reason, we aimed to investigate the underlying processes that may potentially affect cognition by examining brain functional connectivity in nineteen SCLC patients after chemotherapy treatment, while additionally including fourteen healthy participants as control group. Independent Component Analysis (ICA) is a functional connectivity measure aiming to unravel the temporal correlation between brain regions, which are called brain networks. We focused on two brain networks related to the aforementioned cognitive functions, the Default Mode Network (DMN) and the Task-Positive Network (TPN). Permutation tests were performed between the two groups to assess the differences and control for familywise errors in the statistical parametric maps. ICA analysis showed functional connectivity disruptions within both of the investigated networks. These results, propose a detrimental effect of chemotherapy on brain functioning in the SCLC population.

The role of brain/behavioural systems in prediction of quality of life and coping strategies in cancer patients

Directory of Open Access Journals (Sweden)

Shala Jangi Goujeh Biglou

2014-03-01

Full Text Available Background: It seems that individual differences in personality characteristics are implicated in the incidence and progress of physical diseases and socio-psychological consequences. However, there are a few studies about the role of personality in the prediction of socio-psychological consequences of cancer. The aim of this research was to survey the role of personality in the prediction of socio-psychosocial factors: quality of life and coping strategies. Methods: This research was a descriptive-correlational study in which the sample included fifty cancer patients who were selected through convenience sampling method. To assess the personality differences, quality of life and coping strategies, the Carver and White (1994 BIS/BAS Scales, SF-12 Health Survey and Coping Inventory for Stressful Situation (CISS were used, respectively. The data were analysed by SPSS software using Pearson correlation coefficient and stepwise regression. Results: The findings showed that Both BIS and BAS systems could predict the quality of life (P<0.001, BIS system could explain the emotion-oriented coping strategy (P<0.05 and avoidance-oriented coping stratesy (P<0.01 and BAS system could explain the problem-oriented coping strategy (P<0.001. Conclusion: The findings of this study showed that brain/behavioural systems can predict the quality of life and coping strategies in cancer patients. The identification of these systems in cancer patients can help recognize the persons that are under the risk of poor quality of life or have a higher chance of using inconsistent coping strategies, and execute preventive measures about them.

[A case of rectal cancer with brain metastasis successfully treated with combined modality therapy - a case report].

Science.gov (United States)

Nishimura, Junya; Noda, Eiji; Kitayama, Kishu; Nomura, Shinya; Teraoka, Hitoshi; Nishino, Hiroji; Hirakawa, Kosei

2014-11-01

The authors report their experience in a patient with brain metastasis from rectal cancer who has survived without recurrence after multidisciplinary treatment. A 60-year-old man presented to the Department of Neurosurgery with the primary complaint of spasm of the left side of the face. Examination revealed a tumor 2 cm in diameter in the right frontal lobe. The tumor was suspected to be metastatic, and brain metastasis from rectal cancer was diagnosed. The brain tumor was removed by a neurosurgeon, and the patient was transferred to the Department of Surgery. Removal of the primary lesion in the rectum was attempted, but only colostomy could be performed due to extensive anterior invasion. Postoperatively, 5 courses of capecitabine and oxaliplatin (XELOX) + bevacizumab were administered. The rectal tumor shrank in size, while another mass, suspected to be a lung metastasis, remained unchanged. Therefore, a second surgery on the rectum was scheduled, and abdominoperineal resection of the rectum and lateral lymphadenectomy were performed. Postoperatively, 4 courses of XE LOX therapy were administered. The patient is currently alive without recurrence at 1 year after surgery. Treatment (including timing) for brain metastasis from rectal cancer has not been established and prognosis is poor. However, multidisciplinary treatment may provide the possibility of cure.

A Comparative Study of Personality Traits and Brain Behavioral activation Systems and Inhibition in Women with Cancer, Cardiovascular Diseases and Normal Women

Directory of Open Access Journals (Sweden)

Sohrab Amiri

2017-04-01

Full Text Available Background and Objectives: Chronic diseases are among the most important causes of mortality. The aim of the current study was to compare the Brain/behavioral systems and Dark personality traits of Machiavellianism, narcissism, and psychopathy in cancer, cardiovascular female patients and normal women. Methods: In this study, 60 individuals were selected using available sampling in three groups of 20 cancer patients, cardiovascular patients, and normal subjects. Finally, in order to test the goals and hypotheses of the research, the participants were studied based on Behavioral Activation System and Behavioral Inhibition System, and Dark Triad traits. Data analysis was performed using multivariate ANOVA, univariate ANOVA and post-hoc tests. Results: In this study, there was a significant difference among the three groups in Brain/behavioral systems and traits of Machiavellianism, narcissism, and psychopathy, so that the cancer and cardiovascular patients had higher score in dark triad traits compared to normal individuals. Also, the cancer patients had a higher score in Machiavellianism trait compared to the cardiovascular patients. In the brain/behavioral systems, cardiovascular and cancer patients had higher score in behavioral inhibition system (BIS component compared to the normal individuals in the of behavioral inhibition system (BIS. Also, in the reward seeking subscale of behavioral activation system (BAS-f, cancer patients had a higher score compared to cardiovascular patients, which was significantly different. Conclusion: The results of this study indicated that cancer and cardiovascular patients, have greater extent of social disgusting personality traits as well as behavioral inhibition system as anxiety-predisposing factor.

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.

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Hayashi, Nakamasa; Takahashi, Hideaki; Hasegawa, Yuzo; Higuchi, Fumi; Takahashi, Masamichi; Makino, Keishi; Takagaki, Masatoshi; Akimoto, Jiro; Okuda, Takeshi; Okita, Yoshiko; Mitsuya, Koichi; Hirashima, Yasuyuki; Narita, Yoshitaka; Nakasu, Yoko

2017-06-02

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. 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. 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 Brain Tumor Registry of Japan. 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.

Managing brain metastases patients with and without radiotherapy: initial lessonsfrom a team-based consult service through a multidisciplinary integrated palliative oncology clinic.

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Jung, Hellen; Sinnarajah, Aynharan; Enns, Bert; Voroney, Jon-Paul; Murray, Alison; Pelletier, Guy; Wu, Jackson Sai-Yiu

2013-12-01

A new ambulatory consultative clinic with integrated assessments by palliative care, radiation oncology, and allied health professionals was introduced to (1) assess patients with brain metastases at a regional comprehensive cancer center and (2) inform and guide patients on management strategies, including palliative radiotherapy, symptom control, and end-of-life care issues. We conducted a quality assurance study to inform clinical program development. Between January 2011 and May 2012, 100 consecutive brain metastases patients referred and assessed through a multidisciplinary clinic were evaluated for baseline characteristics, radiotherapy use, and supportive care decisions. Overall survival was examined by known prognostic groups. Proportion of patients receiving end-of-life radiotherapy (death within 30 and 14 days of brain radiotherapy) was used as a quality metric. The median age was 65 years, with non-small cell lung cancer (n = 38) and breast cancer (n = 23) being the most common primary cancers. At least 57 patients were engaged in advance care planning discussions at first consult visit. In total, 75 patients eventually underwent brain radiotherapy, whereas 25 did not. The most common reasons for nonradiotherapy management were patient preference and rapid clinical deterioration. Overall survival for prognostic subgroups was consistent with literature reports. End-of-life brain radiotherapy was observed in 9 % (death within 30 days) and 1 % (within 14 days) of treated patients. By integrating palliative care expertise to address the complex needs of patients with newly diagnosed brain metastases, end-of-life radiotherapy use appears acceptable and improved over historical rates at our institution. An appreciable proportion of patients are not suitable for palliative brain radiotherapy or opt against this treatment option, but the team approach involving nurses, palliative care experts, allied health, and clinical oncologists facilitates

Microenvironment Determinants of Brain Metastasis

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Zhang Chenyu

2011-02-01

Full Text Available Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis.

Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.

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Kesler, Shelli R; Watson, Christa L; Blayney, Douglas W

2015-08-01

Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes. Copyright © 2015 Elsevier Inc. All rights reserved.

Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems

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Viani, Gustavo A; Castilho, Marcus S; Salvajoli, João V; Pellizzon, Antonio Cassio A; Novaes, Paulo E; Guimarães, Flavio S; Conte, Maria A; Fogaroli, Ricardo C

2007-01-01

Brain metastases (BM) are the most common form of intracranial cancer. The incidence of BM seems to have increased over the past decade. Recursive partitioning analysis (RPA) of data from three Radiation Therapy Oncology Group (RTOG) trials (1200 patients) has allowed three prognostic groups to be identified. More recently a simplified stratification system that uses the evaluation of three main prognostics factors for radiosurgery in BM was developed. To analyze the overall survival rate (OS), prognostic factors affecting outcomes and to estimate the potential improvement in OS for patients with BM from breast cancer, stratified by RPA class and brain metastases score (BS-BM). From January 1996 to December 2004, 174 medical records of patients with diagnosis of BM from breast cancer, who received WBRT were analyzed. The surgery followed by WBRT was used in 15.5% of patients and 84.5% of others patients were submitted at WBRT alone; 108 patients (62.1%) received the fractionation schedule of 30 Gy in 10 fractions. Solitary BM was present in 37.9 % of patients. The prognostic factors evaluated for OS were: age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, neurosurgery, chemotherapy, absence extracranial disease, RPA class, BS-BM and radiation doses and fractionation. The OS in 1, 2 and 3 years was 33.4 %, 16.7%, and 8.8 %, respectively. The RPA class analysis showed strong relation with OS (p < 0.0001). The median survival time by RPA class in months was: class I 11.7, class II 6.2 and class III 3.0. The significant prognostic factors associated with better OS were: higher KPS (p < 0.0001), neurosurgery (P < 0.0001), single metastases (p = 0.003), BS-BM (p < 0.0001), control primary tumor (p = 0.002) and absence of extracranial metastases (p = 0.001). In multivariate analysis, the factors associated positively with OS were: neurosurgery (p < 0.0001), absence of extracranial metastases (p <0.0001) and RPA class I (p < 0.0001). Our

Gender, Race, and Survival: A Study in Non-Small-Cell Lung Cancer Brain Metastases Patients Utilizing the Radiation Therapy Oncology Group Recursive Partitioning Analysis Classification

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Videtic, Gregory M.M.; Reddy, Chandana A.; Chao, Samuel T.; Rice, Thomas W.; Adelstein, David J.; Barnett, Gene H.; Mekhail, Tarek M.; Vogelbaum, Michael A.; Suh, John H.

2009-01-01

Purpose: To explore whether gender and race influence survival in non-small-cell lung cancer (NSCLC) in patients with brain metastases, using our large single-institution brain tumor database and the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) brain metastases classification. Methods and materials: A retrospective review of a single-institution brain metastasis database for the interval January 1982 to September 2004 yielded 835 NSCLC patients with brain metastases for analysis. Patient subsets based on combinations of gender, race, and RPA class were then analyzed for survival differences. Results: Median follow-up was 5.4 months (range, 0-122.9 months). There were 485 male patients (M) (58.4%) and 346 female patients (F) (41.6%). Of the 828 evaluable patients (99%), 143 (17%) were black/African American (B) and 685 (83%) were white/Caucasian (W). Median survival time (MST) from time of brain metastasis diagnosis for all patients was 5.8 months. Median survival time by gender (F vs. M) and race (W vs. B) was 6.3 months vs. 5.5 months (p = 0.013) and 6.0 months vs. 5.2 months (p = 0.08), respectively. For patients stratified by RPA class, gender, and race, MST significantly favored BFs over BMs in Class II: 11.2 months vs. 4.6 months (p = 0.021). On multivariable analysis, significant variables were gender (p = 0.041, relative risk [RR] 0.83) and RPA class (p < 0.0001, RR 0.28 for I vs. III; p < 0.0001, RR 0.51 for II vs. III) but not race. Conclusions: Gender significantly influences NSCLC brain metastasis survival. Race trended to significance in overall survival but was not significant on multivariable analysis. Multivariable analysis identified gender and RPA classification as significant variables with respect to survival.

Brain abscess mimicking lung cancer metastases; a case report.

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Asano, Michiko; Fujimoto, Nobukazu; Fuchimoto, Yasuko; Ono, Katsuichiro; Ozaki, Shinji; Kimura, Fumiaki; Kishimoto, Takumi

2013-01-01

A 76-year-old woman came to us because of staggering, fever, dysarthria, and appetite loss. Magnetic resonance imaging (MRI) of the brain revealed multiple masses with surrounding edema. Chest X-ray and computed tomography demonstrated a mass-like lesion in the left lung and left pleural effusion. Lung cancer and multiple brain metastases were suspected. However, the brain lesions demonstrated a high intensity through diffusion-weighted MRI. The finding was an important key to differentiate brain abscesses from lung cancer metastases. Copyright © 2013 Elsevier Inc. All rights reserved.

Efficacy of EGFR-TKI therapy in patients with brain metastases from ...

African Journals Online (AJOL)

Purpose: This meta-analysis aimed to systematically evaluate the efficacy of tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) for patients with brain metastases (BM) from nonsmall- cell lung cancer (NSCLC), and to compare this treatment modality to chemotherapy or radiotherapy. Methods: ...

Childhood Brain Stem Glioma Treatment (PDQ®)—Patient Version

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Childhood brain stem glioma can be a benign (not cancer) or malignant (cancer) condition where abnormal cells form in the tissues of the brain stem. Get information about the symptoms, diagnosis, prognosis, and treatment of newly diagnosed and recurrent childhood brain stem glioma in this expert-reviewed summary.

Identification of prognostic factors in patients with brain metastases: a review of 1292 patients

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Lagerwaard, Frank J.; Levendag, Peter C.; Nowak, Peter J.C.M.; Eijkenboom, Wilhelmina M.H.; Hanssens, Patrick E.J.; Schmitz, Paul I.M.

1999-01-01

Purpose: Prognostic factors in 1292 patients with brain metastases, treated in a single institution were identified in order to determine subgroups of patients suitable for selection in future trials. Materials and Methods: From January 1981 through December 1990, 1292 patients with CT-diagnosed brain metastases were referred to the Department of Radiation Oncology, Daniel den Hoed Cancer Center, Rotterdam. The majority of patients were treated with whole brain radiotherapy (84%), the remainder were treated with steroids only or surgery and radiotherapy. Information on potential prognostic factors (age, sex, performance status, number and distribution of brain metastases, site of primary tumor, histology, interval between primary tumor and brain metastases, systemic tumor activity, serum lactate dehydrogenase, response to steroid treatment, and treatment modality) was collected. Univariate and multivariate analyses were performed to determine significant prognostic factors. Results were compared with literature findings using a review of prognostic factors in 18 published reports. Results: Overall median survival was 3.4 months, with 6-month, 1-year, and 2-year survival percentages of 36%, 12%, and 4% respectively. Survival was statistically significantly different between treatment modalities, with median survival of 1.3 months in patients treated with steroids only, 3.6 months in patients treated with radiotherapy, and 8.9 months in patients treated with neurosurgery followed by radiotherapy (p < 0.0001). Multivariate analysis confirmed literature findings of the major prognostic value of treatment modality on survival of patients with brain metastases. Performance status, response to steroid treatment, systemic tumor activity, and serum lactate dehydrogenase were independent prognostic factors with the strongest impact on survival, second only to treatment modality. Site of primary tumor, age, and number of brain metastases were also identified as prognostic

Impact of immunotherapy among patients with melanoma brain metastases managed with radiotherapy.

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Stokes, William A; Binder, David C; Jones, Bernard L; Oweida, Ayman J; Liu, Arthur K; Rusthoven, Chad G; Karam, Sana D

2017-12-15

Patients with melanoma brain metastases (MBM) have been excluded from trials evaluating immunotherapy in melanoma. As such, immunotherapy's role in MBM is poorly understood, particularly in combination with radiotherapy. The National Cancer Database was queried for patients with MBM receiving brain radiotherapy. They were classified according to immunotherapy receipt. Multivariate Cox regression was performed to identify factors associated with survival. Among 1287 patients, 185 received immunotherapy. Factors associated with improved survival included younger age, academic facility, lower extracranial disease burden, stereotactic radiotherapy, chemotherapy, and immunotherapy. Adding immunotherapy to radiotherapy for MBM is associated with improved survival. Copyright © 2017 Elsevier B.V. All rights reserved.

Hemorrhagic brain metastases

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Takahashi, Motoichiro; Takekawa, S.D.; Suzuki, Kenzo

1986-01-01

Tumor hemorrhage on computed tomography (CT) was found in 14 patients with brain metastases (7 % of two hundred patients with brain metastases), from April 1979 to July 1983. Primary foci of these lesions were the lung (6 patients), breast (2), kidney (2), uterus (2), colon (1) and adrenal gland (1). ''Stroke'' syndrome was the initial presenting symptom in 3 patients; neurological focal sign or symptoms of increased intracranial pressure in the remaining patients. CT demonstrated peritumoral hemorrhage in all patients with solid mass, intratumoral hemorrhage in a few patients and also cerebral or ventricular hemorrhage, which was fatal complication, in 2 patients (colon and breast cancers). A cystic mass with fluid-blood level was noted in a patient with breast cancer. Several predisposing factors including chemotherapy, thrombocytopenia, radiotherapy or combination of these were recognized in 8 patients. Of these, chemotherapy was the most causative factor of tumor hemorrhage. Brain irradiation for hemorrhagic brain metastases was effective for prolongation of mean survival time of these patients as follows; 10 months in irradiated group, whereas 1.5 months in non-irradiated group. (author)

Association of brain cancer with dental x-rays and occupation in Missouri

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Neuberger, J.S.; Brownson, R.C.; Morantz, R.A.; Chin, T.D.

1991-01-01

This investigation of a brain cancer cluster in Missouri used two approaches to investigate associations with potential risk factors. In a case-control study in a rural town, we interviewed surrogates of cases and controls about potential risk factors. We found a statistically significant positive association of brain cancer with reported exposure to dental x-rays. Occupation was not associated with the cluster in the rural town. In a standardized proportional mortality study for the state of Missouri, we calculated the observed and expected proportion of brain cancers by occupation and industry in Missouri decedents. We found that motor vehicle manufacturers, beauty shop workers, managers and administrators, elementary school teachers, and hairdressers and cosmetologists had significantly elevated proportions of brain cancer. Brain tumors are inconsistently associated with occupation in the literature. Further study of brain cancer etiology with respect to dental x-ray exposures seems warranted

Efficacy of EGFR-TKI therapy in patients with brain metastases from ...

African Journals Online (AJOL)

Purpose: This meta-analysis aimed to systematically evaluate the efficacy of tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) for patients with brain metastases (BM) from non- small-cell lung cancer (NSCLC), and to compare this treatment modality to chemotherapy or radiotherapy. Methods: ...

Questionnaire survey of treatment choice for breast cancer patients with brain metastasis in Japan. Results of a nationwide survey by the task force of the Japanese Breast Cancer Society

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Matsumoto, Koji; Ando, Masashi; Yamauchi, Chikako

2009-01-01

A nationwide survey was performed to investigate the current patterns of care for brain metastasis (BM) from breast cancer in Japan. A total of 351 survey questionnaires were sent to community or academic breast oncologists who were members of the Japanese Breast Cancer Society as of December 2005. The questionnaire consists of 40 multiple choice questions in eight categories. Of 240 institutions sent survey questionnaires, 161 (67.1%) answered; 60% of institutions answered with '<5' patients with BM every year; almost half (83 of 161) screened for BM in asymptomatic patients; surgical resection was rarely performed, as ∼75% of institutions (118 of 160 institutions) answered 'none or one case of surgery per year'; 27% (41 of 154) preferred stereotactic radiosurgery (SRS) over whole-brain radiotherapy (WBRT) as the initial treatment in all cases, although ∼70% (100 of 154) of them answered 'depend on cases'. The preference for SRS over WBRT mainly depends on the impressions of breast oncologists about both safety (late normal tissue damage and dementia in WBRT) and efficacy (better local control by SRS). Eighty-one percent (117 of 144) of institutions did not limit the number of SRS sessions as far as technically applicable. SRS is widely used as the first choice for BM from breast cancer in Japan. Considerable numbers of Japanese breast oncologists prefer SRS over WBRT as the initial treatment for BM. A randomized trial comparing SRS and WBRT is warranted. (author)

Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study

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Poujol Sylvain

2010-06-01

Full Text Available Abstract Background Since 1999, patients presenting with brain metastases (BM from breast cancer (BC are treated in our institution with a carmustine (BCNU - methotrexate (MTX combination. We report here our clinical experience regarding this combination. Patients and Methods Patients were treated by a combination of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 day cycle. Treatment was continued until progression or unacceptable toxicity. Results 50 patients were treated between 1999 and 2007. 94% of the patients presented with concomitant extra-cerebral disease. Median number of previous metastatic setting chemotherapy regimens was 2 (0-5. Median number of cycles was 3 (1-20. There were 11 objective responses (23% [95%CI 12-37] among 48 evaluable patients. Median progression-free survival and overall survival (OS were 4.2 (95%CI: 2.8-5.3 and 6.9 (4.2-10.7 months respectively, with a one-year OS rate of 32% (20-46. Median Relative Dose Intensity for BCNU and MTX were 0.98 (0.31-1.1 and 0.96 (0.57-1.66 respectively. There were 2 presumed treatment-related deaths. One patient developed febrile neutropenia. Performance status, BS-BM score and presence of liver metastases were associated with OS in univariate analysis. Conclusions This combination appears to be effective and well tolerated in good performance status BC patients presenting with BM.

Value of stereotactic radiosurgery in patients with multiple brain metastases

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Chen Jie; Lin Zhiguo; Li Qingguo; Shen Hong

2002-01-01

Objective: To analyze the prognostic factors and evaluate the effect of stereotactic radiosurgery for patients with multiple brain metastases. Methods: Comparison was made in 53 such patients treated by stereotactic radiosurgery plus radiotherapy and 53 treated by radiotherapy alone. Patients were matched-paired according to the following criteria: age, Karnofsky performance scale (KPS) before treatment, extent of systemic cancer and number of brain metastasis. Forty patients had stereotactic radiosurgery, 13 patients stereotactic fractionated radiosurgery. In the stereotactic radiosurgery group, the patients were given a mean marginal dose of 20 Gy. Methods of stereotactic fractionated radiosurgery was 4-12 Gy per fraction , twice a week to a total dose of 15-30 Gy. Whole brain radiotherapy was given immediately after stereotactic radiosurgery. For patients treated by radiotherapy alone, the entire brain was treated by 30-40 Gy in 3-4 weeks. Results: The median survival was 11.6 months in stereotactic radiosurgery plus radiotherapy and 6.7 months in radiotherapy alone. The one year survival rate and one year local control rate were 44.3%, 17.1% and 50.9%, 13. 2%. Those with KPS increased after treatment gave 1-year survivals of 69.8% and 30.2%, respectively. The validity rates in CT or MRI three months after treatment were 82.0% and 55.0%. The difference in the two groups was found to be statistically significant (P < 0.01). 23.3% of death in the stereotactic radiosurgery plus radiotherapy group was due to brain metastasis vs 51.0% in the radiotherapy alone group (P < 0.05). Complication of the two groups was similar. Conclusion: Stereotactic radiosurgery plus radiotherapy is superior to radiotherapy alone for multiple brain metastases in improving the local control and ultimate outcome

[Brain metastasis from breast cancer: who?, when? and special considerations about the role of technology in neurosurgery].

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Dutertre, Guillaume; Pouit, Bruno

2011-04-01

Questions about both the place and the role of surgery on brain metastasis from breast cancer are arising more and more frequently in practice due to the increase of brain metastasis in patients suffering from a form of cancer recognized as one of the most recurrent cancers in adults but also one of the most sensitive to general treatments of the systemic disease. With improvements in anaesthesia, in surgical instruments, and in global care, neurosurgery has taken advantage of new techniques such as pre- and even per-operative imagery and also neuronavigation. These techniques enable radical and effective surgical intervention with a high level of safety for the patient, making neurosurgery perfectly competitive with other therapeutic modalities, particularly on functional grounds. As for symptomatic treatments or other anti-metastasis treatments, most situations allow a reflection on the global therapeutic strategy which can be adapted to individual cases depending on the patient's general prognosis. In developing this global therapeutic strategy, surgical treatment is still as relevant as ever.

Brain cancer mortality rates increase with Toxoplasma gondii seroprevalence in France

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Vittecoq, Marion; Elguero, Eric; Lafferty, Kevin D.; Roche, Benjamin; Brodeur, Jacques; Gauthier-Clerc, Michel; Missé, Dorothée; Thomas, Frédéric

2012-01-01

The incidence of adult brain cancer was previously shown to be higher in countries where the parasite Toxoplasma gondii is common, suggesting that this brain protozoan could potentially increase the risk of tumor formation. Using countries as replicates has, however, several potential confounding factors, particularly because detection rates vary with country wealth. Using an independent dataset entirely within France, we further establish the significance of the association between T. gondii and brain cancer and find additional demographic resolution. In adult age classes 55 years and older, regional mortality rates due to brain cancer correlated positively with the local seroprevalence of T. gondii. This effect was particularly strong for men. While this novel evidence of a significant statistical association between T. gondii infection and brain cancer does not demonstrate causation, these results suggest that investigations at the scale of the individual are merited.

Migration Phenotype of Brain-Cancer Cells Predicts Patient Outcomes

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Chris L. Smith

2016-06-01

Full Text Available Glioblastoma multiforme is a heterogeneous and infiltrative cancer with dismal prognosis. Studying the migratory behavior of tumor-derived cell populations can be informative, but it places a high premium on the precision of in vitro methods and the relevance of in vivo conditions. In particular, the analysis of 2D cell migration may not reflect invasion into 3D extracellular matrices in vivo. Here, we describe a method that allows time-resolved studies of primary cell migration with single-cell resolution on a fibrillar surface that closely mimics in vivo 3D migration. We used this platform to screen 14 patient-derived glioblastoma samples. We observed that the migratory phenotype of a subset of cells in response to platelet-derived growth factor was highly predictive of tumor location and recurrence in the clinic. Therefore, migratory phenotypic classifiers analyzed at the single-cell level in a patient-specific way can provide high diagnostic and prognostic value for invasive cancers.

Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

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Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L. [Taian City Central Hospital, Taian, Shandong (China); Jiang, Z.M., E-mail: dmyh2436@126.com [Qianfoshan Hospital of Shandong Province, Shandong University, Ji’nan, Shandong (China)

2018-02-01

Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinibWBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Po0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Po0.05). Although bevacizumabgefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. (author)

Radiation-induced dementia in patients cured of brain metastases

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DeAngelis, L.M.; Delattre, J.Y.; Posner, J.B.

1989-01-01

When a patient with cancer develops a brain metastasis, death is usually imminent, but aggressive treatment in some patients with limited or no systemic disease yields long-term survival. In such patients, delayed deleterious effects of therapy are particularly tragic. We report 12 patients who developed delayed complications of whole brain radiotherapy (WBRT) given as sole treatment (4 patients) or in combination with surgical resection (8 patients). Within 5 to 36 months (median, 14) all patients developed progressive dementia, ataxia, and urinary incontinence causing severe disability in all and leading to death in 7. No patient had tumor recurrence when neurologic symptoms began. Cortical atrophy and hypodense white matter were identified by CT in all. Contrast-enhancing lesions were seen in 3 patients; 2 of the lesions yielded radionecrosis on biopsy. Autopsies on 2 patients revealed diffuse chronic edema of the hemispheric white matter in the absence of tumor recurrence. Corticosteroids and ventriculoperitoneal shunt offered significant but incomplete improvement in some patients. The total dose of WBRT was only 2,500 to 3,900 cGy, but daily fractions of 300 to 600 cGy were employed. We believe that these fractionation schedules, several of which are used commonly, predispose to delayed neurologic toxicity, and that more protracted schedules should be employed for the safe and efficacious treatment of good-risk patients with brain metastases. The incidence of WBRT-induced dementia was only 1.9 to 5.1% in the 2 populations reviewed here; however, this underestimates the incidence because only severely affected patients could be identified from chart review

A Single-Institution Analysis of 126 Patients Treated with Stereotactic Radiosurgery for Brain Metastases

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Kevin B. Harris

2017-05-01

Full Text Available BackgroundThe objective of this study was to report our institutional experience with Gamma Knife® Radiosurgery (GKRS in the treatment of patients with brain metastases.MethodsRetrospectively collected demographic and clinical data on 126 patients with intracranial metastases were reviewed. The patients in our study underwent GKRS at Vidant Medical Center between 2009 and 2014. Kaplan–Meier curves were used to compare survival based on clinical characteristics for univariate analysis, and a Cox proportional hazards model was used for multivariate analysis.ResultsThe median age of the patient population was 62 years. Medicare patients constituted 51% of our patient cohort and Medicaid patients 15%. The most common tumor histologies were non-small cell lung cancer (50%, breast cancer (12.7%, and melanoma (11.9%. The median overall survival time for all patients was 5.8 months. Patients with breast cancer had the longest median survival time of 9.15 months, while patients with melanoma had the shortest median survival time of 2.86 months. On univariate analysis, the following factors were predictors for improved overall survival, ECOG score 0 or 1 vs. 2 or greater (17.0 vs. 1.8 months, p < 0.001, controlled extracranial disease vs. progressive extracranial disease (17.4 vs. 4.6 months, p = 0.0001, recursive partitioning analysis Stage I vs. II–III (18.2 vs. 6.2 months, p < 0.007, multiple GKRS treatments (p = 0.002, prior brain metastasectomy (p = 0.012, and prior chemotherapy (p = 0.021. Age, ethnicity, gender, previous external beam radiation therapy, number of brain metastases, and hemorrhagic vs. non-hemorrhagic tumors were not predictors of longer median survival time. Number of metastatic brain lesions of 1–3 vs. ≥4 (p = 0.051 and insurance status of Medicare/Medicaid vs. commercial insurance approached significance (13.7 vs. 6.8 months, p = 0.08. On multivariate analysis, ECOG

MRI findings of radiation encephalopathy of brain stem after radiotherapy for nasopharyngeal cancer

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Liang Changhong; Li Guoye; Huang Biao; Huang Meiping; Zheng Junhui; Tan Shaoheng; Zeng Qiongxin

1998-01-01

Purpose: To study MRI findings and clinical manifestation of radiation encephalopathy (RE) of brain stem. Methods: MRI findings and clinical symptoms in 51 patients with RE of brain stem after radiotherapy for nasopharyngeal cancer were reviewed. Results: Clinical symptoms included number weakness or paralysis in the limbs and symptoms of damaged cranial nerves. All lesions appeared hypo- or iso-intense on spin echo(SE) T 1 -weighted images and inhomogeneous and mixed hyper- and iso-intense on Turbo spin echo (TSE) T 2 -weighted images. The lesions were located in mesencephalon, pons, medulla, basilar part of pons, basilar part of pons and medulla oblongata in 2,7,3,9 and 30 patients respectively. The enhancement patterns included irregular rings in 39 patients, spotty in 3 and no enhancement in 9 patients. Mass effect was minimal in all patients. On follow-up MRI, the lesions disappeared in 4 patients, did not change in size and shape in 8 patients and enlarged in 2 patients. Conclusion: MRI could demonstrate the characteristic findings of RE of brain stem. MRI findings sometimes are not consistent with the clinical symptoms

Brain Injury After Proton Therapy or Carbon Ion Therapy for Head-and-Neck Cancer and Skull Base Tumors

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Miyawaki, Daisuke; Murakami, Masao; Demizu, Yusuke; Sasaki, Ryohei; Niwa, Yasue; Terashima, Kazuki; Nishimura, Hideki; Hishikawa, Yoshio; Sugimura, Kazuro

2009-01-01

Purpose: To assess the incidence of early delayed or late morbidity of Brain after particle therapy for skull base tumors and head-and-neck cancers. Methods and Materials: Between May 2001 and December 2005, 59 patients with cancerous invasion of the skull base were treated with proton or carbon ion therapy at the Hyogo Ion Beam Medical Center. Adverse events were assessed according to the magnetic resonance imaging findings (late effects of normal tissue-subjective, objective, management, analytic [LENT-SOMA]) and symptoms (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0). Dose-volume histograms were used to analyze the relationship between the dose and volume of the irradiated brain and the occurrence of brain injury. The median follow-up time was 33 months. Results: Of the 48 patients treated with proton therapy and 11 patients treated with carbon ion radiotherapy, 8 (17%) and 7 (64%), respectively, developed radiation-induced brain changes (RIBCs) on magnetic resonance imaging (LENT-SOMA Grade 1-3). Four patients (7%) had some clinical symptoms, such as vertigo and headache (CTCAE Grade 2) or epilepsy (CTCAE Grade 3). The actuarial occurrence rate of RIBCs at 2 and 3 years was 20% and 39%, respectively, with a significant difference in the incidence between the proton and carbon ion radiotherapy groups. The dose-volume histogram analyses revealed significant differences between Brain lobes with and without RIBCs in the actuarial volume of brain lobes receiving high doses. Conclusion: Particle therapies produced minimal symptomatic brain toxicities, but sequential evaluation with magnetic resonance imaging detected a greater incidence of RIBCs. Significant differences were observed in the irradiated brain volume between Brain lobes with and without RIBCs.

Validation and Development of a Modified Breast Graded Prognostic Assessment As a Tool for Survival in Patients With Breast Cancer and Brain Metastases.

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Subbiah, Ishwaria M; Lei, Xiudong; Weinberg, Jeffrey S; Sulman, Erik P; Chavez-MacGregor, Mariana; Tripathy, Debu; Gupta, Rohan; Varma, Ankur; Chouhan, Jay; Guevarra, Richard P; Valero, Vicente; Gilbert, Mark R; Gonzalez-Angulo, Ana M

2015-07-10

Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky performance score. However, number of brain metastases-a highly relevant clinical variable-is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases. Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index. In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P formative part of the clinician's discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials. © 2015 by American Society of Clinical Oncology.

Is a diagnostic CT of the brain indicated in patients with choroidal metastases before radiotherapy?

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Bottke, D.; Wiegel, T.; Hoecht, S.; Hinkelbein, W.; Kreusel, K.M.

2005-01-01

Background and purpose: there is no evidence in the literature about the incidence of synchronous brain metastases in patients with choroidal metastases. This is of major importance, because the radiation fields of choroidal metastases and, later on, brain metastases, if treated consecutively, are partly overlapping, thus potentially increasing the rate of late side effects such as brain necrosis. The goal of this study was to determine the frequency of synchronous brain metastases. Patients and methods: 50 patients with choroidal metastases were enrolled into a study of the ''Arbeitsgemeinschaft Radiologische Onkologie'' of the German Cancer Society (ARO 95-08) with standardized 40 Gy radiotherapy, 2 Gy single dose. All patients were staged before treatment with a computed tomography of the brain (CCT). No patient showed clinical signs of brain metastases. Results: 13 out of 50 patients (26%) had brain metastases in the CCT leading to radiotherapy of the brain and choroidal metastases in one volume. Conclusion: a CCT is indicated at the diagnosis of choroidal metastases for screening of synchronous brain metastases. The incidence is about 25%, and the diagnosis of brain metastases results in a different target volume: the whole brain including the posterior parts of the eyes compared to the posterior parts of the eyes alone. Therefore, the risk of late side effects could be reduced compared with an additional later radiotherapy of the whole brain with partly overlapping fields. (orig.)

Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial

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Mulvenna, Paula; Nankivell, Matthew; Barton, Rachael; Faivre-Finn, Corinne; Wilson, Paula; McColl, Elaine; Moore, Barbara; Brisbane, Iona; Ardron, David; Holt, Tanya; Morgan, Sally; Lee, Caroline; Waite, Kathryn; Bayman, Neil; Pugh, Cheryl

2016-01-01

Summary Background Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life. Methods The Quality of Life a...

Follow-up of cognitive functioning in patients with small cell lung cancer

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Oosterhout, Ansel G.M. van; Boon, Peter J; Houx, Peter J; Velde, Guul P.M. ten; Twijnstra, Albert

1995-02-15

Purpose: Study of the course of possible treatment-related cognitive impairment in patients with small cell lung cancer. Methods and Materials: Thirty-two consecutive patients with small cell lung cancer underwent successive neurologic and neuropsychologic examinations until 5 months after prophylactic cranial irradiation, and in their pretherapeutic condition were compared to matched controls. Patients with brain metastases were excluded from this study. Results: Neurologic examination revealed central nervous system (CNS) abnormalities only in the 14 patients with brain metastases. In the remaining patients, neuropsychologic tests showed clear differences between the pretherapeutic performance of patients and that of matched controls (p < 0.001), but no significant deterioration either during or after therapy (0.1 < p < 0.8). Conclusion: The difference between the pretherapeutic performance of patients and that of matched controls may indicate disease-related cognitive impairment. Within the observation period, no adverse effects of the used therapy were found. Our observations underline the importance of a pretherapeutic assessment in neurotoxicity research.

Follow-up of cognitive functioning in patients with small cell lung cancer

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Oosterhout, Ansel G.M. van; Boon, Peter J.; Houx, Peter J.; Velde, Guul P.M. ten; Twijnstra, Albert

1995-01-01

Purpose: Study of the course of possible treatment-related cognitive impairment in patients with small cell lung cancer. Methods and Materials: Thirty-two consecutive patients with small cell lung cancer underwent successive neurologic and neuropsychologic examinations until 5 months after prophylactic cranial irradiation, and in their pretherapeutic condition were compared to matched controls. Patients with brain metastases were excluded from this study. Results: Neurologic examination revealed central nervous system (CNS) abnormalities only in the 14 patients with brain metastases. In the remaining patients, neuropsychologic tests showed clear differences between the pretherapeutic performance of patients and that of matched controls (p < 0.001), but no significant deterioration either during or after therapy (0.1 < p < 0.8). Conclusion: The difference between the pretherapeutic performance of patients and that of matched controls may indicate disease-related cognitive impairment. Within the observation period, no adverse effects of the used therapy were found. Our observations underline the importance of a pretherapeutic assessment in neurotoxicity research

Prognostic factors and multidisciplinary treatment modalities for brain metastases from colorectal cancer: analysis of 93 patients

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Gu, Xiao-Dong; Cai, Yan-Tao; Zhou, Yi-Ming; Li, Zhen-Yang; Xiang, Jian-Bin; Chen, Zong-You

2015-01-01

The purpose of this study was to review patient characteristics and evaluate the potential factors affecting prognosis in cases of brain metastasis (BM) from colorectal cancer (CRC). We retrospectively reviewed 93 cases of BM from CRC in our hospital. Patient demographics, neurologic symptoms, and location and number of BMs were recorded. Factors analyzed included: age; sex; Karnofsky performance score; number of BMs; presence of extracranial metastases; dimensions; location of tumors; treatment modalities. The overall 1- and 2-year survival rates were 27.7 and 9.9 %. On multivariate analysis, the number of BMs, extracranial metastases and the initial treatment modalities were found to be independent prognostic factors for overall survival. Patients treated with surgical resection followed by WBRT or SRS had an improved prognosis relative to those treated with surgery alone (P = 0.02 and P = 0.02, respectively). No significance difference in survival rate was found between patients treated with SRS alone or SRS plus WBRT (P = 0.11). Surgical resection of BMs from CRC in selected patients may help prolong survival. Additional radiotherapy following surgery is valuable in improving prognosis. Extracranial metastasis, multiple BM lesions and initial non operation can be considered as independent factors associated with poor prognosis

Brain Metastases from Breast Cancer and Response to Treatment with Eribulin: A Case Series

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Alex Y. Chang

2015-01-01

Full Text Available Brain metastases are common in patients with advanced breast cancer (BC, causing considerable morbidity and mortality. Eribulin is a microtubule dynamics inhibitor approved for treating certain patients with metastatic BC, previously treated with an anthracycline and a taxane. In the 301 phase 3 study in 1102 women with advanced BC, eribulin and capecitabine treatments did not differ for co-primary endpoints (overall survival [OS]: 15.9 vs 14.5 months, P = 0.056; progression-free survival [PFS]: 4.1 vs 4.2 months, P = 0.30. Here, we report outcomes for six patients (eribulin, n = 3; capecitabine, n = 3 who had received treatment for brain metastases from BC (BCBM at baseline. All eribulin-treated patients experienced brain lesion shrinkage at some point during treatment, compared with one capecitabine-treated patient. Fewer patients in study 301 developed new BCBM with eribulin (13/544, 2.4% compared with capecitabine (25/546, 4.6%. Eribulin does not cross the healthy blood–brain barrier (BBB, but could have the potential to do so after cranial radiation therapy. Capecitabine may cross the BBB and has demonstrated activity in BCBM. Data from these patients and previous cases suggest that further investigation of eribulin for BCBM may be warranted.

Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

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Rades, Dirk; Nadrowitz, Roger; Buchmann, Inga; Meller, Birgit; Hunold, Peter; Noack, Frank; Schild, Steven E.

2010-01-01

Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m 2 cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m 2 cetuximab (cold antibody) were given. Weekly doses of 250 mg/m 2 cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab ( 123 I-Erbi) on scintigraphy; 123 I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

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Rades, Dirk; Nadrowitz, Roger [Dept. of Radiation Oncology, Univ. of Luebeck (Germany); Buchmann, Inga; Meller, Birgit [Section of Nuclear Medicine, Univ. of Luebeck (Germany); Hunold, Peter [Dept. of Radiology, Univ. of Luebeck (Germany); Noack, Frank [Inst. of Pathology, Univ. of Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

2010-08-15

Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m{sup 2} cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m{sup 2} cetuximab (cold antibody) were given. Weekly doses of 250 mg/m{sup 2} cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab ({sup 123}I-Erbi) on scintigraphy; {sup 123}I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

Olanzapine and Betamethasone Are Effective for the Treatment of Nausea and Vomiting due to Metastatic Brain Tumors of Rectal Cancer

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M. Suzuki

2014-01-01

Full Text Available Brain lesions originating from metastasis of colorectal cancer represent 3-5% of all brain metastases and are relatively rare. Of all distant metastases of colorectal cancer, those to the liver are detected in 22-29% of cases, while those to the lungs are detected in 8-18% of cases. In contrast, brain metastasis is quite rare, with a reported incidence ranging from 0.4 to 1.8%. Treatments for metastatic brain tumors include surgery, radiotherapy, chemotherapy and supportive care with steroids, etc. Untreated patients exhibit a median survival of only approximately 1 month. The choice of treatment for brain metastasis depends on the number of lesions, the patient's general condition, nerve findings and presence of other metastatic lesions. We herein report the case of a 78-year-old male who presented with brain metastases originating from rectal carcinoma. He suffered from nausea, vomiting, anorexia and vertigo during body movement. He received antiemetics, glycerol and whole brain radiation therapy; however, these treatments proved ineffective. Olanzapine therapy was started at a dose of 1.25 mg every night. The persistent nausea disappeared the next day, and the frequency of vomiting subsequently decreased. The patient was able to consume solid food. Olanzapine is an antipsychotic that has recently been used as palliative therapy for refractory nausea and vomiting in patients receiving chemotherapy. We consider that olanzapine was helpful as a means of supportive care for the treatment of nausea and vomiting due to brain metastasis.

Association of Ki-67, p53, and bcl-2 expression of the primary non-small-cell lung cancer lesion with brain metastatic lesion

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Bubb, Robbin S.; Komaki, Ritsuko; Hachiya, Tsutomu; Milas, Ivan; Ro, Jae Y.; Langford, Lauren; Sawaya, Raymond; Putnam, Joe B.; Allen, Pamela; Cox, James D.; McDonnell, Timothy J.; Brock, William; Hong, Waun K.; Roth, Jack A.; Milas, Luka

2002-01-01

Purpose: The study was conducted to determine whether immunohistochemical analysis of Ki-67, p53, and bcl-2 in patients with non-small-cell lung cancer is associated with a higher rate of brain metastases and whether the intrapatient expression of these biomarkers (in the primary tumors vs. brain lesions) is similar. Methods and Materials: At the M. D. Anderson Cancer Center, tumors from 29 case patients with primary lung tumor and brain metastasis and 29 control patients with primary lung tumor but no brain metastasis were resected and examined for immunohistochemical expression. Ki-67, p53, and bcl-2 were analyzed in resected primary lung, lymph node, and metastatic brain tumors. Each control patient was matched by age, gender, and histology to a patient with brain metastasis. Results: No significant differences in patient survival characteristics were detected between the case group and control group. Also, difference in patient outcome between the two groups was not generally predicted by biomarker analysis. However, when the groups were combined, the biomarker analysis was predictive for certain patient outcome end points. Using median values as cutoff points between low and high expression of biomarkers, it was observed that high expression of Ki-67 (>40%) in lung primaries was associated with poorer disease-free survival (p=0.04), whereas low expression of p53 in lung primaries was associated with poorer overall survival (p=0.04), and these patients had a higher rate of nonbrain distant metastases (p=0.02). The patients with brain metastases were particularly prone to developing nonbrain distant metastases if the percentage of p53-positive cells in brain metastases was low (p=0.01). There was a positive correlation in the expression of Ki-67 (p=0.02) (r 2 =0.1608), as well as p53 (p 2 =0.7380), between lung primaries and brain metastases. Compared to Ki-67 and p53, bcl-2 was the least predictive. Conclusion: Differences in biomarker expression between the

A radiologic study by CT scan of pineal size in cancer patients

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Tagliabue, M.; Macchi, I.; Salvini, E.; Lissoni, P.; Tancini, G.; Barni, S.; Crispino, S.

1989-01-01

Alterations in size of the pineal body and melatonin secretion have been observed in cancer patients. The present study was carried out to evaluate pineal dimension in a group of cancer patients and their relation to melatonin blood levels. The study included 70 oncologic patients. As controls, 41 patients with acute or chronic disease other than cancer entered the study. Melatonin serum levels were measured by radioimmunoassay on venous blood samples collected at 9:00 a.m. Pineal size was determined by brain CT scan, by considering the product of the two longest perpendicular diameters, multiplied by the thickness of the stratum. The volume of the pineal body was found to be enlarged in 12/70 (17%) cancer patients, and its mean value was significantly higher than that observed in controls. Melatonin levels were also significantly higher in oncologic patients than in controls. However, there was no correlation between melatonin levels and pineal size in cancer patients. Finally, cancer patients did not show a higher degree of pineal calcifications than controls. The clinical significance of pineal enlargement in cancer patients remains to be understood

[Actual questions about the prevention of venous thromboembolism in cancer patients receiving chemotherapy].

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Losonczy, Hajna; Nagy, Ágnes; Tar, Attila

2016-02-07

Cancer patients have a 2-7 fold increased risk of venous thromboembolism compared with the general population and, since 1990, this is associated with significant morbidity and mortality. This review summarizes the current knowledge on venous thromboembolism and cancer. Notably, the risk of venous thromboembolism varies depending on the type and stage of cancer. For instance, pancreatic and brain cancer patients have a higher risk of venous thromboembolism than breast and prostate cancer patients. Moreover, patients with metastatic disease have a higher risk than those with localized tumors. Tumor-derived procoagulant factors, cytokines and growth factors may directly and indirectly enhance venous thromboembolism. Chemotherapy produces ~6,5 fold increase in venous thromboembolism incidence in cancer patients compared to the general population. Prevention of this complication is challenging. The authors review the development of guidelines concerning venous thromboembolism prevention in hospitalized and also in ambulatory cancer patients treated with chemotherapy. Current guidelines recommend the use of low-molecular-weight heparin. Understanding the underlying mechanisms may allow the development of new therapies to safely prevent venous thromboembolism in cancer patients.

Stereotactic Radiosurgery in the Management of Patients With Brain Metastases of Non-Small Cell Lung Cancer: Indications, Decision Tools and Future Directions

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Dianne Hartgerink

2018-05-01

Full Text Available Brain metastases (BM frequently occur in non-small cell lung cancer (NSCLC patients. Most patients with BM have a limited life expectancy, measured in months. Selected patients may experience a very long progression-free survival, for example, patients with a targetable driver mutation. Traditionally, whole-brain radiotherapy (WBRT has been the cornerstone of the treatment, but its indication is a matter of debate. A randomized trial has shown that for patients with a poor prognosis, WBRT does not add quality of life (QoL nor survival over the best supportive care. In recent decades, stereotactic radiosurgery (SRS has become an attractive non-invasive treatment for patients with BM. Only the BM is irradiated to an ablative dose, sparing healthy brain tissue. Intracranial recurrence rates decrease when WBRT is administered following SRS or resection but does not improve overall survival and comes at the expense of neurocognitive function and QoL. The downside of SRS compared with WBRT is a risk of radionecrosis (RN and a higher risk of developing new BM during follow-up. Currently, SRS is an established treatment for patients with a maximum of four BM. Several promising strategies are currently being investigated to further improve the indication and outcome of SRS for patients with BM: the effectivity and safety of SRS in patients with more than four BM, combining SRS with systemic therapy such as targeted agents or immunotherapy, shared decision-making with SRS as a treatment option, and individualized isotoxic dose prescription to mitigate the risk of RN and further enhance local control probability of SRS. This review discusses the current indications of SRS and future directions of treatment for patients with BM of NSCLC with focus on the value of SRS.

Brain tumour stem cells: implications for cancer therapy and regenerative medicine.

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Sanchez-Martin, Manuel

2008-09-01

The cancer relapse and mortality rate suggest that current therapies do not eradicate all malignant cells. Currently, it is accepted that tumorigenesis and organogenesis are similar in many respects, as for example, homeostasis is governed by a distinct sub-population of stem cells in both situations. There is increasing evidence that many types of cancer contain their own stem cells: cancer stem cells (CSC), which are characterized by their self-renewing capacity and differentiation ability. The investigation of solid tumour stem cells has gained momentum particularly in the area of brain tumours. Gliomas are the most common type of primary brain tumours. Nearly two-thirds of gliomas are highly malignant lesions with fast progression and unfortunate prognosis. Despite recent advances, two-year survival for glioblastoma (GBM) with optimal therapy is less than 30%. Even among patients with low-grade gliomas that confer a relatively good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells endowed with features of primitive neural progenitor cells and a tumour-initiating function. In general, this fraction is characterized for forming neurospheres, being endowed with drug resistance properties and often, we can isolate some of them using sorting methods with specific antibodies. The molecular characterization of these stem populations will be critical to developing an effective therapy for these tumours with very dismal prognosis. To achieve this aim, the development of a mouse model which recapitulates the nature of these tumours is essential. This review will focus on glioma stem cell knowledge and discuss future implications in brain cancer therapy and regenerative medicine.

Exposure to magnetic field and brain cancer among child

International Nuclear Information System (INIS)

Mir, L.

2008-01-01

The risk of childhood brain cancer as a function of magnetic field exposure has been studied less than the risk of leukemia. this updated meta-analysis of thirteen epidemiologic studies thus provides an important contribution to the literature. No increased risk of brain cancer was found, and there were no differences by method of exposure assessment. Doubt remains only for the highest exposure levels, for which very limited data are available. (author)

Mechanisms and Therapy for Cancer Metastasis to the Brain

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Federica Franchino

2018-05-01

Full Text Available Advances in chemotherapy and targeted therapies have improved survival in cancer patients with an increase of the incidence of newly diagnosed brain metastases (BMs. Intracranial metastases are symptomatic in 60–70% of patients. Magnetic resonance imaging (MRI with gadolinium is more sensitive than computed tomography and advanced neuroimaging techniques have been increasingly used in the detection, treatment planning, and follow-up of BM. Apart from the morphological analysis, the most effective tool for characterizing BM is immunohistochemistry. Molecular alterations not always reflect those of the primary tumor. More sophisticated methods of tumor analysis detecting circulating biomarkers in fluids (liquid biopsy, including circulating DNA, circulating tumor cells, and extracellular vesicles, containing tumor DNA and macromolecules (microRNA, have shown promise regarding tumor treatment response and progression. The choice of therapeutic approaches is guided by prognostic scores (Recursive Partitioning Analysis and diagnostic-specific Graded Prognostic Assessment-DS-GPA. The survival benefit of surgical resection seems limited to the subgroup of patients with controlled systemic disease and good performance status. Leptomeningeal disease (LMD can be a complication, especially in posterior fossa metastases undergoing a “piecemeal” resection. Radiosurgery of the resection cavity may offer comparable survival and local control as postoperative whole-brain radiotherapy (WBRT. WBRT alone is now the treatment of choice only for patients with single or multiple BMs not amenable to surgery or radiosurgery, or with poor prognostic factors. To reduce the neurocognitive sequelae of WBRT intensity modulated radiotherapy with hippocampal sparing, and pharmacological approaches (memantine and donepezil have been investigated. In the last decade, a multitude of molecular abnormalities have been discovered. Approximately 33% of patients with non

Comparison of erlotinib and pemetrexed as second-/third-line treatment for lung adenocarcinoma patients with asymptomatic brain metastases

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He YY

2016-04-01

Full Text Available Yayi He,1,* Wenwen Sun,2,* Yan Wang,3,* Shengxiang Ren,1 Xuefei Li,3 Jiayu Li,3 Christopher J Rivard,4 Caicun Zhou,1 Fred R Hirsch4 1Department of Oncology, Shanghai Pulmonary Hospital, 2Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, 3Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, USA *These authors contributed equally to this work Objective: Brain metastases occur in one-third of all non-small-cell lung cancer patients. Due to restrictive transport at the blood–brain barrier, many drugs provide poor control of metastases in the brain. The aim of this study was to compare erlotinib with pemetrexed as second-/third-line treatment in patients with lung adenocarcinoma with asymptomatic brain metastases.Methods: From January 2012 to June 2014, all lung adenocarcinoma patients with asymptomatic brain metastases who received treatment with erlotinib or pemetrexed as second-/third-line treatment were retrospectively reviewed. Chi-square and log-rank tests were used to perform statistical analysis.Results: The study enrolled 99 patients, of which 44 were positive for EGFR mutation. Median progression-free survival (PFS in months was not significantly different between the erlotinib- and pemetrexed-treated groups (4.2 vs 3.4 months; 95% confidence interval [CI]: 2.01–6.40 vs 2.80–5.00, respectively; P=0.635. Median PFS was found to be significantly longer in EGFR mutation–positive patients in the erlotinib-treated group (8.0 months; 95% CI 5.85–10.15 compared to the pemetrexed group (3.9 months; 95% CI: 1.25–6.55; P=0.032. The most common treatment-related side effect was mild-to-moderate rash and the most common drug-related side

Trends in brain cancer mortality among U.S. Gulf War veterans: 21 year follow-up.

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Barth, Shannon K; Dursa, Erin K; Bossarte, Robert M; Schneiderman, Aaron I

2017-10-01

Previous mortality studies of U.S. Gulf War veterans through 2000 and 2004 have shown an increased risk of brain cancer mortality among some deployed individuals. When veterans possibly exposed to environmental contaminants associated with demolition of the Khamisiyah Ammunition Storage Facility at Khamisiyah, Iraq, have been compared to contemporaneously deployed unexposed veterans, the results have suggested increased risk for mortality from brain cancer among the exposed. Brain cancer mortality risk in this cohort has not been updated since 2004. This study analyzes the risk for brain cancer mortality between 1991-2011 through two series of comparisons: U.S. Gulf War deployed and non-deployed veterans from the same era; and veterans possibly exposed to environmental contaminants at Khamisiyah compared to contemporaneously deployed but unexposed U.S. Gulf War veterans. Risk of brain cancer mortality was determined using logistic regression. Life test hazard models were created to plot comparisons of annual hazard rates. Joinpoint regression models were applied to assess trends in hazard rates for brain cancer mortality. U.S. Army veterans possibly exposed at Khamisiyah had similar rates of brain cancer mortality compared to those not possibly exposed; however, veterans possibly exposed had a higher risk of brain cancer in the time period immediately following the Gulf War. Results from these analyses suggest that veterans possibly exposed at Khamisiyah experienced different patterns of brain cancer mortality risk compared to the other groups. Published by Elsevier Ltd.

Quality of Life in Patients With Primary and Metastatic Brain Tumors in the Literature as Assessed by the FACT-Br.

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Chiu, Nicholas; Chiu, Leonard; Zeng, Liang; Zhang, Liying; Cella, David; Popovic, Marko; Chow, Ronald; Lam, Henry; Poon, Michael; Chow, Edward

2012-12-01

The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a quality of life (QOL) assessment tool that was originally developed for use in patients with primary brain tumors. However, the tool has also been used to assess QOL in patients with metastatic brain tumors. The purpose of this study is to compare the differences in QOL responses as assessed by the FACT-Br in patients with primary and metastatic brain neoplasms. A systematic literature search was conducted using the OvidSP platform in MEDLINE (1946 to July Week 2 2012) and EMBASE (1980 to 2012 Week 28). Articles in which the FACT-Br was used as a QOL assessment for patients with malignant brain tumors (both primary and metastatic) were included in the study. The weighted means of FACT-Br subscale and overall scores were calculated for the studies. To compare these scores, weighted analysis of variance was conducted and PROC GLM was performed for the data. A P-value of Br for assessment of QOL were identified. Social and functional well-being were significantly better in patients with primary brain tumors (weighted mean score of 22.2 vs. 10.7, P = 0.0026, 16.9 vs. 6.2, P = 0.0025, respectively). No other scale of the FACT-Br was significantly different between the two groups and the performance status of patients included in both groups was similar. Patients with primary brain cancer seemed to have better social and functional well-being scores than those with metastatic brain tumors. Other QOL domains were similar between these two groups. However, the heterogeneity in the included studies and the low sample size of included samples in patients with metastatic brain tumors could have confounded our findings.

Efficacy and safety of icotinib in patients with brain metastases from lung adenocarcinoma

OpenAIRE

Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2016-01-01

Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China Objective: The objective of this study was to evaluate the efficacy and safety of icotinib in patients with brain metastases (BMs) from lung adenocarcinoma.Patients and methods: Clinical data of 28 cases with BMs from lung adenocarcinoma were retrospectively analyzed. All the patients took 125&am...

Ultrasound imaging-guided intracardiac injection to develop a mouse model of breast cancer brain metastases followed by longitudinal MRI.

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Zhou, Heling; Zhao, Dawen

2014-03-06

Breast cancer brain metastasis, occurring in 30% of breast cancer patients at stage IV, is associated with high mortality. The median survival is only 6 months. It is critical to have suitable animal models to mimic the hemodynamic spread of the metastatic cells in the clinical scenario. Here, we are introducing the use of small animal ultrasound imaging to guide an accurate injection of brain tropical breast cancer cells into the left ventricle of athymic nude mice. Longitudinal MRI is used to assessing intracranial initiation and growth of brain metastases. Ultrasound-guided intracardiac injection ensures not only an accurate injection and hereby a higher successful rate but also significantly decreased mortality rate, as compared to our previous manual procedure. In vivo high resolution MRI allows the visualization of hyperintense multifocal lesions, as small as 310 µm in diameter on T2-weighted images at 3 weeks post injection. Follow-up MRI reveals intracranial tumor growth and increased number of metastases that distribute throughout the whole brain.

Improving Care in Pediatric Neuro-oncology Patients: An Overview of the Unique Needs of Children With Brain Tumors.

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Fischer, Cheryl; Petriccione, Mary; Donzelli, Maria; Pottenger, Elaine

2016-03-01

Brain tumors represent the most common solid tumors in childhood, accounting for almost 25% of all childhood cancer, second only to leukemia. Pediatric central nervous system tumors encompass a wide variety of diagnoses, from benign to malignant. Any brain tumor can be associated with significant morbidity, even when low grade, and mortality from pediatric central nervous system tumors is disproportionately high compared to other childhood malignancies. Management of children with central nervous system tumors requires knowledge of the unique aspects of care associated with this particular patient population, beyond general oncology care. Pediatric brain tumor patients have unique needs during treatment, as cancer survivors, and at end of life. A multidisciplinary team approach, including advanced practice nurses with a specialty in neuro-oncology, allows for better supportive care. Knowledge of the unique aspects of care for children with brain tumors, and the appropriate interventions required, allows for improved quality of life. © The Author(s) 2015.

Efficacy and adverse effects of icotinib in treatment of 30 NSCLC patients with brain metastases

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Yu-hong DAI

2016-06-01

Full Text Available Objective 　To evaluate the efficacy and adverse effects of icotinib in the treatment for non-small cell lung cancer (NSCLC patients with brain metastases. Methods 　This study was performed at Tongji Hospital Cancer Center over the period between September 2011 and November 2015. Thirty cases of advanced NSCLC patients with icotinib monotherapy were enrolled, all with brain metastases, the median follow-up time being 24 months (5.5-49.0 months, with no case censored. The follow-up rate was 100%, and the data of efficacy and adverse effects were collected. Results 　The intracranial progression-free survival (iPFS was 9.6 months, while no patient exhibited complete remission (CR, 8 patients showed partial remission (PR and 14 showed stable disease (SD in the intracranial foci. The intracranial disease control rate (DCR was 73.3%, and the objective remission rate (ORR was 26.7%. The extracranial progression-free survival (ePFS was 10.1 months, while no patient exhibited CR, 11 patients showed PR and 11 patients showed SD in the extracranial foci. The extracranial DCR was 73.3%, and the ORR was 36.7%. The one-year survival rate was 63.8% in all the 30 patients. Twelve (40.0% of the total 30 patients developed rash, five (16.7% developed grade 1 diarrhea, one (3.3% developed grade 2 transaminase elevation. None of the patients experienced headache, nausea, vomiting, fatigue, etc. Conclusion 　Icotinib hydrochloride is effective and safe for NSCLC patients with brain metastasis. DOI: 10.11855/j.issn.0577-7402.2016.06.11

Altered resting brain connectivity in persistent cancer related fatigue

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Johnson P. Hampson

2015-01-01

Full Text Available There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI. Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected. This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52 and poor sleep quality (P = 0.04, r = 0.52 in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected. Mental fatigue scores were associated with greater default mode network (DMN connectivity to the superior frontal gyrus (P = 0.05 FDR corrected among fatigued subjects (r = 0.82 and less connectivity in the non-fatigued group (r = −0.88. These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent

Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases

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Atalar, Banu [Department of Radiation Oncology, Acibadem University School of Medicine, Istanbul (Turkey); Modlin, Leslie A. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Choi, Clara Y.H.; Adler, John R. [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Gibbs, Iris C. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Chang, Steven D.; Harsh, Griffith R.; Li, Gordon [Department of Neurosurgery, Stanford University Medical Center, Stanford, California (United States); Nagpal, Seema [Department of Neurology, Stanford University Medical Center, Stanford, California (United States); Hanlon, Alexandra [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Soltys, Scott G., E-mail: sgsoltys@stanford.edu [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States)

2013-11-15

Purpose: We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients. Methods and Materials: We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other). Results: With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004). Conclusions: In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

Incidental findings on brain Magnetic Resonance Imaging in long-term survivors of breast cancer treated with adjuvant chemotherapy.

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Koppelmans, Vincent; Schagen, Sanne B; Poels, Mariëlle M F; Boogerd, Willem; Seynaeve, Caroline; van der Lugt, Aad; Breteler, Monique M B

2011-11-01

Incidental brain findings defined as previously undetected abnormalities of potential clinical relevance that are unexpectedly discovered at brain imaging and are unrelated to the purpose of the examination are common in the general population. Because it is unclear whether the prevalence of incidental findings in breast cancer patients treated with chemotherapy is different to that in the general population, we compared the prevalence in breast cancer survivors treated with chemotherapy to that in a population-based sample of women without a history of any cancer. Structural brain MRI (1.5T) was performed in 191 female CMF (Cyclophosphamide, Methotrexate, 5-Fluorouracil) chemotherapy-exposed breast cancer survivors. A reference group of 1590 women without a history of cancer was sampled from a population-based cohort study. All participants were aged 50 to 80 years. Five trained reviewers recorded the brain abnormalities. Two experienced neuro-radiologists reviewed the incidental findings. The cancer survivors had completed chemotherapy on average 21 years before. Of the 191 subjects, 2.6% had an aneurysm and 3.7% had a meningioma. The prevalence of meningiomas and aneurysms was not different between the groups. The prevalence of pituitary macro adenomas in the breast cancer survivors (1.6%) was higher than that in the reference group (0.1%) (OR=23.7; 95% CI 2.3-245.8). Contrary to commonly held opinions, we did not observe an increased prevalence of meningiomas in cancer survivors. Breast cancer survivors previously treated with chemotherapy are more likely to develop pituitary adenomas than persons without a history of cancer and chemotherapy treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Non-small cell lung cancer brain metastasis screening in the era of positron emission tomography-CT staging: Current practice and outcomes.

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Diaz, Mauricio E; Debowski, Maciej; Hukins, Craig; Fielding, David; Fong, Kwun M; Bettington, Catherine S

2018-05-10

Several clinical guidelines indicate that brain metastasis screening (BMS) should be guided by disease stage in non-small cell lung cancer (NSCLC). We estimate that screening is performed more broadly in practice, and patients undergo brain imaging at considerable cost with questionable benefit. Our aim was to quantify the use and detection rate of BMS in a contemporary cohort staged with 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT). We conducted a retrospective review of prospectively collected data from three major lung cancer referral centres in Brisbane between January 2011 and December 2015. Patients included had a new diagnosis of NSCLC and had undergone a PET-CT to stage extra-cranial disease. BMS was defined as dedicated brain imaging with contrast-enhanced computed tomography (CE-CT) or magnetic resonance (MR), in the absence of clinically apparent neurological deficits. A total of 1751 eligible cases were identified and of these 718 (41%) underwent BMS. The majority had CE-CT imaging (n = 703). Asymptomatic brain metastases (BM) were detected in 18 patients (2.5%). Of these patients, 12 had concurrent non-brain metastases. Only six patients (0.8%) had BM alone. The rate of detection increased with N-stage (P = 0.02) and overall stage (P < 0.001). It was 0.5%, 1%, 1.6% and 7.3% for stage I, II, III and IV respectively. The overall screening rate increased with T-stage (P = 0.001), N-Stage (P < 0.001) and overall stage (P < 0.001). Non-small cell lung cancer BMS practices remain at odds with published guidelines. The low number of occult BMs detected supports the existing international recommendations. Rationalising BMS would minimise the burden on patients and the health care system. © 2018 The Royal Australian and New Zealand College of Radiologists.

Risk of Developing Second Cancer From Neutron Dose in Proton Therapy as Function of Field Characteristics, Organ, and Patient Age

International Nuclear Information System (INIS)

Zacharatou Jarlskog, Christina; Paganetti, Harald

2008-01-01

Purpose: To estimate the risk of a second malignancy after treatment of a primary brain cancer using passive scattered proton beam therapy. The focus was on the cancer risk caused by neutrons outside the treatment volume and the dependency on the patient's age. Methods and Materials: Organ-specific neutron-equivalent doses previously calculated for eight different proton therapy brain fields were considered. Organ-specific models were applied to assess the risk of developing solid cancers and leukemia. Results: The main contributors (>80%) to the neutron-induced risk are neutrons generated in the treatment head. Treatment volume can influence the risk by up to a factor of ∼2. Young patients are subject to significantly greater risks than are adult patients because of the geometric differences and age dependency of the risk models. Breast cancer should be the main concern for females. For males, the risks of lung cancer, leukemia, and thyroid cancer were significant for pediatric patients. In contrast, leukemia was the leading risk for an adult. Most lifetime risks were <1% (70-Gy treatment). The only exceptions were breast, thyroid, and lung cancer for females. For female thyroid cancer, the treatment risk can exceed the baseline risk. Conclusion: The risk of developing a second malignancy from neutrons from proton beam therapy of a brain lesion is small (i.e., presumably outweighed by the therapeutic benefit) but not negligible (i.e., potentially greater than the baseline risk). The patient's age at treatment plays a major role

Taurine-modified Ru(ii)-complex targets cancerous brain cells for photodynamic therapy.

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Du, Enming; Hu, Xunwu; Roy, Sona; Wang, Peng; Deasy, Kieran; Mochizuki, Toshiaki; Zhang, Ye

2017-05-30

The precision and efficacy of photodynamic therapy (PDT) is essential for the treatment of brain tumors because the cancer cells are within or adjacent to the delicate nervous system. Taurine is an abundant amino acid in the brain that serves the central nervous system (CNS). A taurine-modified polypyridyl Ru-complex was shown to have optimized intracellular affinity in cancer cells through accumulation in lysosomes. Symmetrical modification of this Ru-complex by multiple taurine molecules enhanced the efficiency of molecular emission with boosted generation of reactive oxygen species. These characteristic features make the taurine-modified Ru-complex a potentially effective photosensitizer for PDT of target cancer cells, with outstanding efficacy in cancerous brain cells.

Delayed Development of Brain Abscesses Following Stent-Graft Placement in a Head and Neck Cancer Patient Presenting with Carotid Blowout Syndrome

International Nuclear Information System (INIS)

Oweis, Yaseen; Gemmete, Joseph J.; Chaudhary, Neeraj; Pandey, Aditya; Ansari, Sameer

2011-01-01

We describe the delayed development of intracranial abscesses following emergent treatment with a covered stent-graft for carotid blowout syndrome (CBS) in a patient with head and neck cancer. The patient presented with hemoptysis and frank arterial bleeding through the tracheostomy site. A self-expandable stent-graft was deployed across a small pseudoaneurysm arising from the right common carotid artery (RCCA) and resulted in immediate hemostasis. Three months later, the patient suffered a recurrent hemorrhage. CT of the neck demonstrated periluminal fluid around the caudal aspect of the stent-graft with intraluminal thrombus and a small pseudoaneurysm. Subsequently, the patient underwent a balloon test occlusion study and endovascular sacrifice of the RCCA and right internal carotid artery. MRI of the brain demonstrated at least four ring-enhancing lesions within the right cerebral hemisphere consistent with intracranial abscesses that resolved with broad-spectrum antibiotic coverage.

Translation and pilot validation of Hindi translation of assessing quality of life in patients with primary brain tumours using EORTC brain module (BN-20

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Budrukkar Ashwini

2006-01-01

Full Text Available Aim: To translate and validate the European Organisation for Research and Treatment for Cancer (EORTC brain cancer module (BN-20 into Hindi to make it available for patients and scientific community. Methods and Results: The EORTC BN-20 was translated into Hindi using standard guidelines by EORTC. The process included forward translation by two translators, discussion with the translators in case of discrepancies and formation of first intermediate questionnaire. This questionnaire was then given to two more translators who translated this questionnaire back into English. These 2 questionnaires were then compared with the original EORTC questionnaire and the second intermediate questionnaire was formed. The second intermediate questionnaire was subsequently administered in 10 patients with brain tumors who had never seen the questionnaire before, for pilot-testing. Each of these 10 patients after filling up the questionnaire themselves was then interviewed for any difficulty encountered during the filling up of the questionnaire. These were in the form of specific modules including difficulty in answering, confusion while answering and difficulty to understand, whether the questions were upsetting and if patients would have asked the question in any different way. There were major suggestions in three questions, which were incorporated into the second intermediate questionnaire to form the final Hindi BN-20 questionnaire. Conclusion: The final Hindi BN-20 has been approved by EORTC and can be used in clinical practice and studies for patients with brain tumors.

Metachronous brain and intramedullary spinal cord metastases from nonsmall-cell lung cancer: A case report

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Wen-Chih Liu

2012-05-01

Full Text Available A 44-year-old man had a brain tumor secondary to lung adenocarcinoma and underwent craniectomy to remove the brain tumor. After postoperative whole-brain radiation therapy, he underwent pneumonectomy followed by chemotherapy, mediastinal radiotherapy, and target therapy for lung cancer. Thirty-six months after the initial brain surgery, he suffered from neck pain and right upper limb numbness that rapidly progressed to upper extremity weakness and paralysis in 2 months. Magnetic resonance imaging demonstrated an intramedullary spinal cord lesion at the C4 level. Laminectomy and gross intramedullary tumor removal were performed. The patient’s neurological function improved after the operation. Nevertheless, 4 months after the intramedullary tumor removal, he began to show multiple metastases. Unfortunately, the patient died from respiratory failure 8 months after diagnosis with intramedullary spinal cord metastasis. In this case, early diagnosis and aggressive surgical treatment combined with postoperative radiotherapy and chemotherapy might have provided this patient with a prolonged survival and better quality of life.

Complete remission through icotinib treatment in Non-small cell lung cancer epidermal growth factor receptor mutation patient with brain metastasis: A case report

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Wang Tao

2016-01-01

Full Text Available Brain metastasis (BM has been universally recognized as a poor prognostic factor in non-small cell lung cancer (NSCLC. Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs have shown efficacy in treating BM with an EGFR mutation. This paper reports a case of BM patient with EGFR-mutated NSCLC. According to the findings, a complete remission (CR of the BM was achieved by icotinib treatment without conducting a radiotherapy, which was followed by a resection of the primary lung cancer lesion and lymph nodes. After one-year follow-up, the disease progressed to liver metastasis and liver lesion biopsy showed a T790M mutation. The patient responded well to the combination treatment of AZD9291 and icotinib after the failure of transcatheter arterial chemoembolization (TACE. This case report suggests that icotinib has a sustainable anticancer response to BM and the combination with icotinib and AZD9291 is effective for liver metastasis with T790M.

Overall Survival After Whole-Brain Radiation Therapy for Intracerebral Metastases from Testicular Cancer.

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Rades, Dirk; Dziggel, Liesa; Veninga, Theo; Bajrovic, Amira; Schild, Steven E

2016-09-01

To identify predictors and develop a score for overall survival of patients with intracerebral metastasis from testicular cancer. Whole-brain radiation therapy program, age, Karnofsky performance score (KPS), number of intracerebral metastases, number of other metastatic sites and time between testicular cancer diagnosis and radiation therapy were analyzed for their association with overall survival in eight patients. KPS of 80-90% was significantly associated with better overall survival (p=0.006), one or no other metastatic sites showed a trend for a better outcome (p=0.10). The following scores were assigned: KPS 60-70%=0 points, KPS 80-90%=1 point, ≥2 other metastatic sites=0 points, 0-1 other metastatic sites=1 point. Two groups, with 0 and with 1-2 points, were formed. Overall survival rates were 33% vs. 100% at 6 months and 0% vs. 100% at 12 months (p=0.006), respectively. A simple instrument enabling physicians to judge the overall survival of patients with intracerebral metastasis from testicular cancer is provided. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

A mathematical theory of shape and neuro-fuzzy methodology-based diagnostic analysis: a comparative study on early detection and treatment planning of brain cancer.

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Kar, Subrata; Majumder, D Dutta

2017-08-01

Investigation of brain cancer can detect the abnormal growth of tissue in the brain using computed tomography (CT) scans and magnetic resonance (MR) images of patients. The proposed method classifies brain cancer on shape-based feature extraction as either benign or malignant. The authors used input variables such as shape distance (SD) and shape similarity measure (SSM) in fuzzy tools, and used fuzzy rules to evaluate the risk status as an output variable. We presented a classifier neural network system (NNS), namely Levenberg-Marquardt (LM), which is a feed-forward back-propagation learning algorithm used to train the NN for the status of brain cancer, if any, and which achieved satisfactory performance with 100% accuracy. The proposed methodology is divided into three phases. First, we find the region of interest (ROI) in the brain to detect the tumors using CT and MR images. Second, we extract the shape-based features, like SD and SSM, and grade the brain tumors as benign or malignant with the concept of SD function and SSM as shape-based parameters. Third, we classify the brain cancers using neuro-fuzzy tools. In this experiment, we used a 16-sample database with SSM (μ) values and classified the benignancy or malignancy of the brain tumor lesions using the neuro-fuzzy system (NFS). We have developed a fuzzy expert system (FES) and NFS for early detection of brain cancer from CT and MR images. In this experiment, shape-based features, such as SD and SSM, were extracted from the ROI of brain tumor lesions. These shape-based features were considered as input variables and, using fuzzy rules, we were able to evaluate brain cancer risk values for each case. We used an NNS with LM, a feed-forward back-propagation learning algorithm, as a classifier for the diagnosis of brain cancer and achieved satisfactory performance with 100% accuracy. The proposed network was trained with MR image datasets of 16 cases. The 16 cases were fed to the ANN with 2 input neurons, one

Impact of whole brain radiation therapy on CSF penetration ability of Icotinib in EGFR-mutated non-small cell lung cancer patients with brain metastases: Results of phase I dose-escalation study.

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Zhou, Lin; He, Jiazhuo; Xiong, Weijie; Liu, Yongmei; Xiang, Jing; Yu, Qin; Liang, Maozhi; Zhou, Xiaojuan; Ding, Zhenyu; Huang, Meijuan; Ren, Li; Zhu, Jiang; Li, Lu; Hou, Mei; Ding, Lieming; Tan, Fenlai; Lu, You

2016-06-01

Whole-brain radiation therapy (WBRT) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are both treatment options for EGFR-mutated non-small cell lung cancer (NSCLC) patients with brain metastases. However, the dose-escalation toxicity and efficacy of combination therapy, and the effect of WBRT on cerebrospinal fluid (CSF) penetration of EGFR-TKIs are still unclear. EGFR-mutated NSCLC patients with brain metastases were enrolled in this study, and the cohorts were constructed with a 3+3 design. The patients received icotinib with escalating doses (125-625mg, tid), and the concurrent WBRT (37.5Gy/15f/3weeks) started a week later. The CSF penetration rates of icotinib were tested before, immediately after, and 4 weeks after WBRT, respectively. Potential toxicities and benefits from dose-escalation treatment were analyzed. Fifteen patients were included in this study, 3 at each dose level from 125mg-375mg and 6 at 500mg with 3 occurred dose-limiting toxicities. The maximal tolerated dose of icotinib was 375mg tid in this combination therapy. There was a significant correlation between icotinib concentration in the CSF and plasma (R(2)=0.599, Picotinib, from 1.2% to 9.7%, reached a maximum at 375mg (median, 6.1%). There was no significant difference for CSF penetration rates among the three test points (median, 4.1% vs. 2.8% vs. 2.8%, P=0.16). The intracranial objective response rate and median intracranial progression free survival are 80% and 18.9 months. WBRT plus concurrent icotinib is well tolerated in EGFR-mutated NSCLC patients with brain metastases, up to an icotinib dose of 375mg tid. The icotinib CSF concentration seemed to have a potential ceiling effect with the dose escalation, and WBRT seemed to have no significant impact on CSF penetration of icotinib till 4 weeks after the treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Multiple brain metastases - current management and perspectives for treatment with electrochemotherapy

DEFF Research Database (Denmark)

Linnert, Mette; Iversen, Helle Klingenberg; Gehl, Julie

2012-01-01

BACKGROUND: Due to the advanced oncological treatments of cancer, an overall increase in cancer incidence, and better diagnostic tools, the incidence of brain metastases is on the rise. This review addresses the current treatment options for patients with multiple brain metastases, presenting...... of the chemotherapeutic drug bleomycin by 300 times. Preclinical data are promising and the first patient has been treated in an ongoing clinical trial for patients with brain metastases. Perspectives for ECT in the brain include treatment of primary and secondary brain tumors as well as soft tissue metastases elsewhere....

Causes of death of patients with lung cancer.

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Nichols, Larry; Saunders, Rachel; Knollmann, Friedrich D

2012-12-01

The causes of death for patients with lung cancer are inadequately described. To categorize the immediate and contributing causes of death for patients with lung cancer. The autopsies from 100 patients who died of lung cancer between 1990 and February 2011 were analyzed. Tumor burden was judged the immediate cause of death in 30 cases, including 26 cases of extensive metastases and 4 cases with wholly or primarily lung tumor burden (causing respiratory failure). Infection was the immediate cause of death for 20 patients, including 8 with sepsis and 12 with pneumonia. Complications of metastatic disease were the immediate causes of death in 18 cases, including 6 cases of hemopericardium from pericardial metastases, 3 from myocardial metastases, 3 from liver metastases, and 3 from brain metastases. Other immediate causes of death were pulmonary hemorrhage (12 cases), pulmonary embolism (10 cases, 2 tumor emboli), and pulmonary diffuse alveolar damage (7 cases). From a functional (pathophysiologic) perspective, respiratory failure could be regarded as the immediate cause of death (or mechanism of death) in 38 cases, usually because of a combination of lung conditions, including emphysema, airway obstruction, pneumonia, hemorrhage, embolism, resection, and lung injury in addition to the tumor. For 94 of the 100 patients, there were contributing causes of death, with an average of 2.5 contributing causes and up to 6 contributing causes of death. The numerous and complex ways lung cancer kills patients pose a challenge for efforts to extend and improve their lives.

Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

International Nuclear Information System (INIS)

Picano, Eugenio; Vano, Eliseo; Domenici, Luciano; Bottai, Matteo; Thierry-Chef, Isabelle

2012-01-01

According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906), the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of < 200 mSv, but with head exposure which may (in absence of protection) arrive at a head equivalent dose of 1 to 3 Sv after a professional lifetime (corresponding to a brain equivalent dose around 500 mSv). At this point, a systematic assessment of brain (cancer and non-cancer) effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed

PULMONARY EMBOLISM: SOME ISSUES OF EPIDEMIOLOGY AND TREATMENT IN CANCER PATIENTS

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I. D. Rozanov

2015-01-01

Full Text Available The risk of pulmonary embolism (PE in cancer patients  is 4–7-fold, compared to other  patient  categories. PE is the  second  most frequent  cause of death  in the first year after cancer diagnosis. PE is diagnosed in 7.5% of patients with malignant brain tumors, in 1 to 25% of those  with gastrointestinal tumors, in 4.5 to 17.5% of those with breast cancer and in 4 to 10% of lung cancer patients. The risk of PE is higher with surgical interventions and chemotherapy, as well as in metastatic tumors. In 13% of cases, PE may be the first symptom of cancer manifestation. For prevention and treatment of PE low molecular weight heparin (LMWH and warfarin are   used. The risk of recurrent  PE is 2-fold lower with LMWH. The frequency of bleeding with LMWH and warfarin treatment is from 14 to 19%. Placement of a cava filter is indicated  only if anticoagulation is inefficient.  New oral anticoagulants,  which act as selective thrombin  or Factor Xa inhibitors, are not used in cancer patients. Thus, diagnostics and treatment of PE is a very urgent  problem in oncology that requires new approaches to be looked for.

The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

OpenAIRE

Zhou Weihua; Mukherjee Purna; Kiebish Michael A; Markis William T; Mantis John G; Seyfried Thomas N

2007-01-01

Abstract Background Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and su...

Clinical Outcome in Gamma Knife Radiosurgery for Metastatic Brain Tumors from the Primary Breast Cancer : Prognostic Factors in Local Treatment Failure and Survival

OpenAIRE

Choi, Seung Won; Kwon, Do Hoon; Kim, Chang Jin

2013-01-01

Objective Brain metastases in primary breast cancer patients are considerable sources of morbidity and mortality. Gamma knife radiosurgery (GKRS) has gained popularity as an up-front therapy in treating such metastases over traditional radiation therapy due to better neurocognitive function preservation. The aim of this study was to clarify the prognostic factors for local tumor control and survival in radiosurgery for brain metastases from primary breast cancer. Methods From March 2001 to Ma...

Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer.

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Papademetriou, Iason T; Porter, Tyrone

2015-01-01

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood-brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future.

Initial psycho-oncological counselling in neuro-oncology: analysis of topics and needs of brain tumour patients.

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Schipmann, Stephanie; Suero Molina, Eric; Frasch, Anna; Stummer, Walter; Wiewrodt, Dorothee

2018-02-01

Diagnosis of a brain tumour is associated with a tremendous disruption of emotional, physical and social well-being. Due to the complexity of the disease and the affection of the central organ, the brain, brain tumour patients differ from other cancer patients. The purpose of this study was to evaluate the concerns and burdens presented by brain tumour patients during their initial psycho-oncological consultation. We performed a retrospective analysis of 53 patients with the diagnosis of either benign or malignant brain tumour, seeking counsel by a neurosurgeon specialised in psycho-oncology. We performed a thematic analysis of the interviews at first consultation identifying themes and patterns and created thematic categories. The main concerns of the patients presented during the first consultations were psychological problems, reported by 40 patients (75.5%). Death and dying was mentioned by more than half of the patients (n = 30, 56.6%). In addition, 62.3% of the patients (n = 33) asked for information regarding the medical treatment and diagnosis. With our study, we created greater awareness of the psychological needs of brain tumour patients in order to define treatment strategies for this important aspect of disease. We showed that there is a need for patients to talk about death even during the initial consultation. Psycho-oncologist in a neuro-oncological setting should be prepared for topics like that and should have a neurosurgical background or collaborate with members of the surgical team in order to provide the patients with medical details and to better understand the impact of the disease.

Computer screens and brain cancer

International Nuclear Information System (INIS)

Wood, A.W.

1995-01-01

Australia, both in the media and at the federal government level, over possible links between screen-based computer use and cancer, brain tumour in particular. The screen emissions assumed to be the sources of the putative hazard are the magnetic fields responsible for horizontal and vertical scanning of the display. Time-varying fluctuations in these magnetic fields induce electrical current flows in exposed tissues. This paper estimates that the induced current densities in the brain of the computer user are up to 1 mA/m 2 (due to the vertical flyback). Corresponding values for other electrical appliances or installations are in general much less than this. The epidemiological literature shows no obvious signs of a sudden increase in brain tumour incidence, but the widespread use of computers is a relatively recent phenomenon. The occupational use of other equipment based on cathode ray tubes (such as TV repair) has a much longer history and has been statistically linked to brain tumour in some studies. A number of factors make this an unreliable indicator of the risk from computer screens, however. 42 refs., 3 tabs., 2 figs

Validation of the RTOG recursive partitioning analysis (RPA) classification for small-cell lung cancer-only brain metastases

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Videtic, Gregory M.M.; Adelstein, David J.; Mekhail, Tarek M.; Rice, Thomas W.; Stevens, Glen H.J.; Lee, S.-Y.; Suh, John H.

2007-01-01

Purpose: Radiation Therapy Oncology Group (RTOG) developed a prognostic classification based on a recursive partitioning analysis (RPA) of patient pretreatment characteristics from three completed brain metastases randomized trials. Clinical trials for patients with brain metastases generally exclude small-cell lung cancer (SCLC) cases. We hypothesize that the RPA classes are valid in the setting of SCLC brain metastases. Methods and Materials: A retrospective review of 154 SCLC patients with brain metastases treated between April 1983 and May 2005 was performed. RPA criteria used for class assignment were Karnofsky performance status (KPS), primary tumor status (PT), presence of extracranial metastases (ED), and age. Results: Median survival was 4.9 months, with 4 patients (2.6%) alive at analysis. Median follow-up was 4.7 months (range, 0.3-40.3 months). Median age was 65 (range, 42-85 years). Median KPS was 70 (range, 40-100). Number of patients with controlled PT and no ED was 20 (13%) and with ED, 27 (18%); without controlled PT and ED, 34 (22%) and with ED, 73 (47%). RPA class distribution was: Class I: 8 (5%); Class II: 96 (62%); Class III: 51 (33%). Median survivals (in months) by RPA class were: Class I: 8.6; Class II: 4.2; Class III: 2.3 (p = 0.0023). Conclusions: Survivals for SCLC-only brain metastases replicate the results from the RTOG RPA classification. These classes are therefore valid for brain metastases from SCLC, support the inclusion of SCLC patients in future brain metastases trials, and may also serve as a basis for historical comparisons

Insights into brain metastasis in patients with ALK+ lung cancer: is the brain truly a sanctuary?

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Toyokawa, Gouji; Seto, Takashi; Takenoyama, Mitsuhiro; Ichinose, Yukito

2015-12-01

Anaplastic lymphoma kinase (ALK) has been identified to exert a potent transforming activity through its rearrangement in non-small cell lung cancer (NSCLC), and patients (pts) with ALK rearrangement can be treated more successfully with ALK inhibitors, such as crizotinib, alectinib, and ceritinib, than with chemotherapy. Despite the excellent efficacy of ALK inhibitors, resistance to these drugs is inevitably encountered in most ALK-rearranged pts. Cases of resistance are subtyped into three groups, i.e., systemic, oligo, and central nervous system (CNS) types, with the CNS being used to be considered a sanctuary. With regard to the management of CNS lesions in pts with ALK+ NSCLC, a growing body of evidence has gradually demonstrated the intracranial (IC) efficacy of ALK inhibitor (ALKi) in ALK+ NSCLC pts with brain metastases (BMs). Although the efficacy of crizotinib for the CNS lesions remains controversial, a recent retrospective investigation of ALK+ pts with BM enrolled in PROFILE 1005 and PROFILE 1007 demonstrated that crizotinib is associated with a high disease control rate for BM. However, BM comprises the most common site of progressive disease in pts with or without baseline BMs, which is a serious problem for crizotinib. Furthermore, alectinib can be used to achieve strong and long-lasting inhibitory effects on BM. In addition to alectinib, the IC efficacy of other next-generation ALK inhibitors, such as ceritinib, AP26113 and PF-06463922, has been demonstrated. In this article, we review the latest evidence regarding the BM and IC efficacy of ALK inhibitors in pts with ALK+ NSCLC.

Cancers of the Brain and CNS: Global Patterns and Trends in Incidence.

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Mortazavi, S M J; Mortazavi, S A R; Paknahad, M

2018-03-01

Miranda-Filho et al. in their recently published paper entitled "Cancers of the brain and CNS: global patterns and trends in incidence" provided a global status report of the geographic and temporal variations in the incidence of brain and CNS cancers in different countries across continents worldwide. While the authors confirm the role of genetic risk factors and ionizing radiation exposures, they claimed that no firm conclusion could be drawn about the role of exposure to non-ionizing radiation. The paper authored by Miranda-Filho et al. not only addresses a challenging issue, it can be considered as a good contribution in the field of brain and CNS cancers. However, our correspondence addresses a basic shortcoming of this paper about the role of electromagnetic fields and cancers and provides evidence showing that exposure to radiofrequency electromagnetic fields (RF-EMFs), at least at high levels and long durations, can increases the risk of cancer.

Brain magnetic resonance imaging screening is not useful for HIV-1-infected patients without neurological symptoms.

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Nishijima, Takeshi; Gatanaga, Hiroyuki; Teruya, Katsuji; Tajima, Tsuyoshi; Kikuchi, Yoshimi; Hasuo, Kanehiro; Oka, Shinichi

2014-10-01

We investigated the diagnostic usefulness of brain magnetic resonance imaging (MRI) screening in HIV-1-infected patients without neurological symptoms in detecting intracranial diseases at early stages. In this retrospective analysis, the study patients were HIV-1-infected patients who underwent brain MRI scan in clinical practice between 2001 and 2013. We excluded patients with MRI for (1) follow-up examination for prediagnosed intracranial diseases, (2) cancer staging, (3) screening mycobacterium/bacteria/fungi disease proliferation in the brain, and (4) evaluation for meningitis/encephalitis. The study patients (n=485) were classified into two groups: those who underwent brain MRI scan without any neurological symptoms/signs (asymptomatic patients, n=158) and those who underwent MRI due to such symptoms (symptomatic patients, n=327). Asymptomatic patients had lower CD4 counts than symptomatic patients (median 78 versus 241/μl). Intracranial diseases were detected in three (2%) of the asymptomatic patients [two toxoplasmosis and one progressive multifocal leukoencephalopathy (PML)] compared to 58 (19%) of the symptomatic patients (the χ(2) test, pHIV-associated dementia (n=17). Among symptomatic patients, intracranial diseases were common in those with slurred speech (3/6, 50%), seizure (4/10, 40%), eyesight/vision abnormality (5/16, 31%), altered mental status (8/31, 26%), and hemiplegia/numbness (13/50, 26%). For patients with CD4 count HIV-1-infected patients without neurological symptoms is of little value.

Differences in Brain Glucose Metabolism During Preparation for 131I Ablation in Thyroid Cancer Patients: Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin.

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Jeong, Hyeonseok S; Choi, Eun Kyoung; Song, In-Uk; Chung, Yong-An; Park, Jong-Sik; Oh, Jin Kyoung

2017-01-01

In preparation for 131 I ablation, temporary withdrawal of thyroid hormone is commonly used in patients with thyroid cancer after total thyroidectomy. The current study aimed to investigate brain glucose metabolism and its relationships with mood or cognitive function in these patients using 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG-PET). A total of 40 consecutive adult patients with thyroid carcinoma who had undergone total thyroidectomy were recruited for this cross-sectional study. At the time of assessment, 20 patients were hypothyroid after two weeks of thyroid hormone withdrawal, while 20 received thyroid hormone replacement therapy and were euthyroid. All participants underwent brain 18 F-FDG-PET scans and completed mood questionnaires and cognitive tests. Multivariate spatial covariance analysis and univariate voxel-wise analysis were applied for the image data. The hypothyroid patients were more anxious and depressed than the euthyroid participants. The multivariate covariance analysis showed increases in glucose metabolism primarily in the bilateral insula and surrounding areas and concomitant decreases in the parieto-occipital regions in the hypothyroid group. The level of thyrotropin was positively associated with the individual expression of the covariance pattern. The decreased 18 F-FDG uptake in the right cuneus cluster from the univariate analysis was correlated with the increased thyrotropin level and greater depressive symptoms in the hypothyroid group. These results suggest that temporary hypothyroidism, even for a short period, may induce impairment in glucose metabolism and related affective symptoms.

Long-term survival, prevalence, and cure of cancer: a population-based estimation for 818 902 Italian patients and 26 cancer types

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Dal Maso, L.; Guzzinati, S.; Buzzoni, C.; Capocaccia, R.; Serraino, D.; Caldarella, A.; Dei Tos, A. P.; Falcini, F.; Autelitano, M.; Masanotti, G.; Ferretti, S.; Tisano, F.; Tirelli, U.; Crocetti, E.; De Angelis, R.; Virdone, S.; Zucchetto, A.; Gigli, A.; Francisci, S.; Baili, P.; Gatta, G.; Castaing, M.; Zanetti, R.; Contiero, P.; Bidoli, E.; Vercelli, M.; Michiara, M.; Federico, M.; Senatore, G.; Pannozzo, F.; Vicentini, M.; Bulatko, A.; Pirino, D. R.; Gentilini, M.; Fusco, M.; Giacomin, A.; Fanetti, A. C.; Cusimano, R.

2014-01-01

Background Persons living after a cancer diagnosis represent 4% of the whole population in high-income countries. The aim of the study was to provide estimates of indicators of long-term survival and cure for 26 cancer types, presently lacking. Patients and methods Data on 818 902 Italian cancer patients diagnosed at age 15–74 years in 1985–2005 were included. Proportions of patients with the same death rates of the general population (cure fractions) and those of prevalent patients who were not at risk of dying as a result of cancer (cure prevalence) were calculated, using validated mixture cure models, by cancer type, sex, and age group. We also estimated complete prevalence, conditional relative survival (CRS), time to reach 5- and 10-year CRS >95%, and proportion of patients living longer than those thresholds. Results The cure fractions ranged from >90% for patients aged cancers to cancers of all ages. Five- or 10-year CRS >95% were both reached in cancers of the stomach, colon–rectum, pancreas, corpus and cervix uteri, brain, and Hodgkin lymphoma. For breast cancer patients, 5- and 10-year CRSs reached >95% after 19 and 25 years, respectively, and in 15 and 18 years for prostate cancer patients. Five-year CRS remained 25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Overall, the cure prevalence was 67% for men and 77% for women. Therefore, 21% of male and 31% of female patients had already reached 5-year CRS >95%, whereas 18% and 25% had reached 10-year CRS >95%. Conclusions A quarter of Italian cancer patients can be considered cured. This observation has a high potential impact on health planning, clinical practice, and patients' perspective. PMID:25149707

Long term imaging of living brain cancer cells

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Farias, Patricia M. A.; Galembeck, André; Milani, Raquel; Andrade, Arnaldo C. D. S.; Stingl, Andreas

2018-02-01

QDs synthesized in aqueous medium and functionalized with polyethylene glycol were used as fluorescent probes. They label and monitor living healthy and cancer brain glial cells in culture. Physical-chemical characterization was performed. Toxicological studies were performed by in vivo short and long-term inhalation in animal models. Healthy and cancer glial living cells were incubated in culture media with highly controlled QDs. Specific features of glial cancer cells were enhanced by QD labelling. Cytoplasmic labelling pattern was clearly distinct for healthy and cancer cells. Labelled cells kept their normal activity for same period as non-labelled control samples.

Information needs and requirements in patients with brain tumours and their relatives.

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Reinert, Christiane; Rathberger, Katharina; Klinkhammer-Schalke, Monika; Kölbl, Oliver; Proescholdt, Martin; Riemenschneider, Markus J; Schuierer, Gerhard; Hutterer, Markus; Gerken, Michael; Hau, Peter

2018-06-01

Patients with brain tumours face a number of medical and social challenges. Previous studies have shown that these patients and their relatives need a high level of patient-oriented information and counselling. However, these needs are often underestimated. In this single-centre cross-sectional study, we evaluated, for the first time, the information needs of patients with brain tumours and their relatives depending on diagnosis, age and level of education. The participants were interviewed using pre-specified questionnaires. Answers were evaluated descriptively using standard statistical methods. A total of 888 questionnaires were sent out. The return rate was 50.7%. The majority of patients (nP = 103; 59.9%) and a higher proportion of relatives (nR = 103; 72.5%; p = 0.019) wished to receive a maximum of information. The majority (79.7% of patients; 83.1% of relatives) also stated that they preferred a personal, face-to-face meeting as primary source of information. The need for information increased with education (p = 0.015), and decreased with tumour grade (p = 0.025) and age (p = 0.118). Our data indicate that patients with brain tumours and their relatives have high information needs throughout their disease and continuously require information and counselling. Optimal provision of information is based on personal preferences, which needs to be evaluated appropriately. Patient-oriented information and counselling are parts of a successful communication strategy that can improve cancer care significantly.

Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

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Yang, Heekyoung; Yoon, Su Jin; Jin, Juyoun; Choi, Seung Ho; Seol, Ho Jun; Lee, Jung-Il

2011-01-01

Research highlights: → The most important therapeutic tool in brain metastasis is radiation therapy. → Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. → Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. → Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

Management of Brain Metastases.

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Jeyapalan, Suriya A.; Batchelor, Tracy

2004-07-01

Advances in neurosurgery and the development of stereotactic radiosurgery have expanded treatment options available for patients with brain metastases. However, despite several randomized clinical trials and multiple uncontrolled studies, there is not a uniform consensus on the best treatment strategy for all patients with brain metastases. The heterogeneity of this patient population in terms of functional status, types of underlying cancers, status of systemic disease control, and number and location of brain metastases make such consensus difficult. Nevertheless, in certain situations, there is Class I evidence that supports one approach or another. The primary objectives in the management of this patient population include improved duration and quality of survival. Very few patients achieve long-term survival after the diagnosis of a brain metastasis.

Pesticides and brain cancer linked in orchard farmers of Kashmir.

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Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A R; Raina, T H

2010-10-01

-related patients. The significantcase/control odds ratio (OR) of 0.28, hospital control SCE OR of 1.1 and family control SCE OR of 1.5, points the finger of suspicion toward the link between pesticides and brain cancer.

Dynamic glucose enhanced (DGE) MRI for combined imaging of blood-brain barrier break down and increased blood volume in brain cancer.

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Xu, Xiang; Chan, Kannie W Y; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T; van Zijl, Peter C M

2015-12-01

Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared with contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (P blood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. © 2015 Wiley Periodicals, Inc.

Dynamic Glucose Enhanced (DGE) MRI for Combined Imaging of Blood Brain Barrier Break Down and Increased Blood Volume in Brain Cancer

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Xu, Xiang; Chan, Kannie WY; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T.; van Zijl, Peter C.M.

2015-01-01

Purpose Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Methods Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. Results DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared to contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (pblood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. PMID:26404120

Efficacy and safety of icotinib in patients with brain metastases from lung adenocarcinoma

Directory of Open Access Journals (Sweden)

Xu J

2016-05-01

Full Text Available Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China Objective: The objective of this study was to evaluate the efficacy and safety of icotinib in patients with brain metastases (BMs from lung adenocarcinoma.Patients and methods: Clinical data of 28 cases with BMs from lung adenocarcinoma were retrospectively analyzed. All the patients took 125 mg icotinib orally three times a day. Progression of disease, intolerable adverse reactions, and number of deaths were recorded.Results: For all the patients, the remission rate of icotinib was 67.8% and the disease control rate was 96.4%. The median overall survival time of patients was 21.2 months, and the median progression-free survival time of patients was 10.9 months. Only mild adverse events of grade 1/2 were observed during the treatment.Conclusion: Icotinib was an effective and safe strategy to treat patients with BMs from lung adenocarcinoma.Keywords: icotinib, lung adenocarcinoma, brain metastases 

Offspring of patients treated for cancer in childhood

International Nuclear Information System (INIS)

Li, F.P.; Fine, W.; Jaffe, N.; Holmes, G.E.; Holmes, F.F.

1979-01-01

Genetic effects of cancer in childhood were examined among offspring of patients enrolled in the tumor registries of the Sidney Farber Cancer Institute and the Kansas University Medical Center. For 146 patients, 84 women and 62 men, 293 pregnancies were reported after cessation of treatment of diverse neoplasms. The outcomes of 286 completed pregnancies were as follows: 242 live births (1 set of twins), 1 stillbirth, 25 spontaneous abortions, and 19 therapeutic abortions. Seven live-born infants died during the first 2 years of life, a frequency in accord with expectation. Two offspring have developed cancer. One girl and her father had bilateral hereditary retinoblastoma. A second girl developed acute myelocytic leukemia; her mother had received radiotherapy during childhood for a brain tumor. Compared with their cousins and with published figures for the general population, the study progeny had no excess of congenital anomalles or other diseases. Chromosome and immunoglobulin studies of a few offspring did not reveal damage from preconception exposure to cancer chemotherapy and radiotherapy. Findings indicated that large collaborative studies are needed to monitor the offspring of childhood cancer survivors for inherited traits associated with the parental tumors and for mutagenic effects of therapy, particularly intense multimodality treatments

Place of death of pediatric cancer patients in a single institute during 7 years.

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Yanai, Tomoko; Hirase, Satoshi; Matsunoshita, Natsuki; Yamamoto, Nobuyuki; Ninchoji, Takeshi; Kubokawa, Ikuko; Mori, Takeshi; Hayakawa, Akira; Takeshima, Yasuhiro; Iijima, Kazumoto; Matsuo, Masafumi

2012-06-27

Place of death is an important issue at the end-of-life. It is poorly understood in pediatric cancer patients in Japan. This study aimed to clarify place of death of children with cancer as well as variables associated with place of death. Study population was pediatric cancer patients who died in the Department of Pediatrics at Kobe University Hospital during the last 7 years. The medical records were retrospectively reviewed regardless of cause of death to derive data relating to patients' characteristics and disease. 18 patients were included. Median age at death was 12.2 years old. 6 patients including 5 children in complete remission had hematological disease and 12 patients suffered from solid tumors. 4 patients (22.2%) died at home, whereas 14 patients (77.8%) died in the hospital including 6 ICU deaths. No one died in hospices. Preference of patients was unavailable due to the lack of inquiry. Factors influencing place of death (home, ICU, non-ICU) were disease (hematological disease vs. solid tumor, p=0.010, brain tumor vs. non-brain tumor, p=0.023), disease status (complete remission vs. non-complete remission, p=0.0014) and preference of families (p=0.029). Among 6 families who expressed preference, no disparity was observed between actual and preferred place of death. This is the first English publication of place of death of pediatric cancer patients in Japan. The low percentage of home death, factors influencing place of death and the lack of disparity between actual and preferred place of death were indicated. Further studies are required to better understand place of death.

Microwave beamforming for non-invasive patient-specific hyperthermia treatment of pediatric brain cancer

International Nuclear Information System (INIS)

Burfeindt, Matthew J; Zastrow, Earl; Hagness, Susan C; Van Veen, Barry D; Medow, Joshua E

2011-01-01

We present a numerical study of an array-based microwave beamforming approach for non-invasive hyperthermia treatment of pediatric brain tumors. The transmit beamformer is designed to achieve localized heating-that is, to achieve constructive interference and selective absorption of the transmitted electromagnetic waves at the desired focus location in the brain while achieving destructive interference elsewhere. The design process takes into account patient-specific and target-specific propagation characteristics at 1 GHz. We evaluate the effectiveness of the beamforming approach using finite-difference time-domain simulations of two MRI-derived child head models from the Virtual Family (IT'IS Foundation). Microwave power deposition and the resulting steady-state thermal distribution are calculated for each of several randomly chosen focus locations. We also explore the robustness of the design to mismatch between the assumed and actual dielectric properties of the patient. Lastly, we demonstrate the ability of the beamformer to suppress hot spots caused by pockets of cerebrospinal fluid (CSF) in the brain. Our results show that microwave beamforming has the potential to create localized heating zones in the head models for focus locations that are not surrounded by large amounts of CSF. These promising results suggest that the technique warrants further investigation and development.

Brain Tumor’s Radioresistance: The Neighborhood Helps | Center for Cancer Research

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Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. The primary treatment for GBM is radiation therapy. Unfortunately, while some patients initially respond, the vast majority of GBM patients fail radiotherapy, and the tumor usually grows back within two years. To gain a better understanding of the biological basis for GBM resistance to radiation, researchers initially studied GBM cell lines in vitro. In recent years, the focus has been on so-called tumor stem-like cells (TSCs), which are thought to be responsible for driving and maintaining tumor growth. To the researchers’ surprise, TSCs grown in vitro did not have the same ability to resist radiation as TSCs in the GBM tumors.

Recurrently Mutated Genes Differ between Leptomeningeal and Solid Lung Cancer Brain Metastases.

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Li, Yingmei; Liu, Boxiang; Connolly, Ian David; Kakusa, Bina Wasunga; Pan, Wenying; Nagpal, Seema; Montgomery, Stephen B; Hayden Gephart, Melanie

2018-03-29

When compared with solid brain metastases from NSCLC, leptomeningeal disease (LMD) has unique growth patterns and is rapidly fatal. Patients with LMD do not undergo surgical resection, limiting the tissue available for scientific research. In this study we performed whole exome sequencing on eight samples of LMD to identify somatic mutations and compared the results with those for 26 solid brain metastases. We found that taste 2 receptor member 31 gene (TAS2R31) and phosphodiesterase 4D interacting protein gene (PDE4DIP) were recurrently mutated among LMD samples, suggesting involvement in LMD progression. Together with a retrospective review of the charts of an additional 44 patients with NSCLC LMD, we discovered a surprisingly low number of KRAS mutations (n = 4 [7.7%]) but a high number of EGFR mutations (n = 33 [63.5%]). The median interval for development of LMD from NSCLC was shorter in patients with mutant EGFR (16.3 months) than in patients with wild-type EGFR (23.9 months) (p = 0.017). Targeted analysis of recurrent mutations thus presents a useful complement to the existing diagnostic tool kit, and correlations of EGFR in LMD and KRAS in solid metastases suggest that molecular distinctions or systemic treatment pressure underpin the differences in growth patterns within the brain. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Treatment of metastatic brain lesion

Directory of Open Access Journals (Sweden)

A. M. Zaytsev

2015-01-01

Full Text Available Objective. Increasing survival in patients with secondary brain damage, and identifying the factors of favorable and adverse prognosis.Material and method. In P. A. Hertsen Moscow Oncology Research Institute from 2007 to 2013 there were treated 268 patients with brain metastases. The mean age was 55.8 years (from 24 to 81 years. Metastases of colorectal cancer identified in 7.8%, cases of lung cancer in 34%, melanoma 9.3 %, breast cancer in 26%, kidney cancer in 11%, with non-identified primary tumor in 4.5%, other tumors accounted for 6.7%. Solitary metastasis was diagnosed in 164 (61,19% patients, oligometastasis (2-3 - 72 (26,87% patients with polymetastasis (more than 3 – 32 (11,94% patients. In 106 (39,55% of patients with brain metastases it was the only manifestation of the generalization process. To control the radical removal of the tumor in 93 (34,7% patients we used the method of fluorescence navigation (FN with the drug Alasens. In 66 (24,6% patients intraoperatively was held a session of photodynamic therapy (PDT. In 212 (79,1% cases, the removal of metastasis performed totally, 55 (20,9% patients stated Subtotal removal.Results. The observation period for the patients ranged from 3 to 79 months. Survival median among the entire group of patients with metastatic brain lesion was 12 months. Overall survival was significantly dependent on RPA class, the volume of postoperative treatment, histological type of primary tumor, number of intracerebral metastases and the timing of the relapse-free period.Conclusions. Factors that affects the overall survival are the features of the histology of the primary lesion, multiplicity of metastatic lesions, RPA class and the synchronous nature of the metastasis. The median of overall survival of patients who did not receive after surgical treatment of a particular type of therapy was only 4 months. If to use the combined treatment (surgical treatment with the irradiation of the whole brain median

Paraneoplastic brain stem encephalitis.

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Blaes, Franz

2013-04-01

Paraneoplastic brain stem encephalitis can occur as an isolated clinical syndrome or, more often, may be part of a more widespread encephalitis. Different antineuronal autoantibodies, such as anti-Hu, anti-Ri, and anti-Ma2 can be associated with the syndrome, and the most frequent tumors are lung and testicular cancer. Anti-Hu-associated brain stem encephalitis does not normally respond to immunotherapy; the syndrome may stabilize under tumor treatment. Brain stem encephalitis with anti-Ma2 often improves after immunotherapy and/or tumor therapy, whereas only a minority of anti-Ri positive patients respond to immunosuppressants or tumor treatment. The Opsoclonus-myoclonus syndrome (OMS) in children, almost exclusively associated with neuroblastoma, shows a good response to steroids, ACTH, and rituximab, some patients do respond to intravenous immunoglobulins or cyclophosphamide. In adults, OMS is mainly associated with small cell lung cancer or gynecological tumors and only a small part of the patients show improvement after immunotherapy. Earlier diagnosis and treatment seem to be one major problem to improve the prognosis of both, paraneoplastic brain stem encephalitis, and OMS.

Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial.

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Mulvenna, Paula; Nankivell, Matthew; Barton, Rachael; Faivre-Finn, Corinne; Wilson, Paula; McColl, Elaine; Moore, Barbara; Brisbane, Iona; Ardron, David; Holt, Tanya; Morgan, Sally; Lee, Caroline; Waite, Kathryn; Bayman, Neil; Pugh, Cheryl; Sydes, Benjamin; Stephens, Richard; Parmar, Mahesh K; Langley, Ruth E

2016-10-22

Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life. The Quality of Life after Treatment for Brain Metastases (QUARTZ) study is a non-inferiority, phase 3 randomised trial done at 69 UK and three Australian centres. NSCLC patients with brain metastases unsuitable for surgical resection or stereotactic radiotherapy were randomly assigned (1:1) to optimal supportive care (OSC) including dexamethasone plus WBRT (20 Gy in five daily fractions) or OSC alone (including dexamethasone). The dose of dexamethasone was determined by the patients' symptoms and titrated downwards if symptoms improved. Allocation to treatment group was done by a phone call from the hospital to the Medical Research Council Clinical Trials Unit at University College London using a minimisation programme with a random element and stratification by centre, Karnofsky Performance Status (KPS), gender, status of brain metastases, and the status of primary lung cancer. The primary outcome measure was quality-adjusted life-years (QALYs). QALYs were generated from overall survival and patients' weekly completion of the EQ-5D questionnaire. Treatment with OSC alone was considered non-inferior if it was no more than 7 QALY days worse than treatment with WBRT plus OSC, which required 534 patients (80% power, 5% [one-sided] significance level). Analysis was done by intention to treat for all randomly assigned patients. The trial is registered with ISRCTN, number ISRCTN3826061. Between March 2, 2007, and Aug 29, 2014, 538 patients were recruited from 69 UK and three Australian centres, and were randomly assigned to

Role of prophylactic brain irradiation in limited stage small cell lung cancer: clinical, neuropsychologic, and CT sequelae

International Nuclear Information System (INIS)

Laukkanen, E.; Klonoff, H.; Allan, B.; Graeb, D.; Murray, N.

1988-01-01

Ninety-four patients with limited stage small cell lung cancer treated between 1981 and 1985 with a regimen including prophylactic brain irradiation (PBI) after combination chemotherapy were assessed for compliance with PBI, brain relapse, and neurologic morbidity. Seventy-seven percent of patients had PBI and of these, 22% developed brain metastases after a median time of 11 months post treatment. The brain was the apparent unique initial site of relapse in 10% of PBI cases but more commonly brain relapse was preceded or accompanied by failure at other sites, especially the chest. Brain metastases were the greatest cause of morbidity in 50% of PBI failures. Twelve of 14 PBI patients alive 2 years after treatment had oncologic, neurologic, and neuropsychological evaluation, and brain CT. All long-term survivors were capable of self care and none fulfilled diagnostic criteria for dementia, with three borderline cases. One third had pretreatment neurologic dysfunction and two thirds post treatment neurologic symptoms, most commonly recent memory loss. Fifty percent had subtle motor findings. Intellectual functioning was at the 38th percentile with most patients having an unskilled occupational history. Neuropsychologic impairment ratings were borderline in three cases and definitely impaired in seven cases. CT scans showed brain atrophy in all cases with mild progression in those having a pre-treatment baseline. Periventricular and subcortical low density lesions identical to the CT appearance of subcortical arteriosclerotic encephalopathy were seen in 82% of posttreatment CT studies, and lacunar infarcts in 54%. Neuropsychologic impairment scores and the extent of CT periventricular low density lesions were strongly associated

Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer

OpenAIRE

Papademetriou, Iason T; Porter, Tyrone

2015-01-01

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers non...

Efficacy of prophylactic cranial irradiation in patients with limited-disease small-cell lung cancer who were confirmed to have no brain metastasis via magnetic resonance imaging after initial chemoradiotherapy

Science.gov (United States)

Mamesaya, Nobuaki; Wakuda, Kazushige; Omae, Katsuhiro; Miyawaki, Eriko; Kotake, Mie; Fujiwara, Takumi; Kawamura, Takahisa; Kobayashi, Haruki; Nakashima, Kazuhisa; Omori, Shota; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Murakami, Haruyasu; Mori, Keita; Harada, Hideyuki; Endo, Masahiro; Nakajima, Takashi; Takahashi, Toshiaki

2018-01-01

Background Prophylactic cranial irradiation (PCI) is recommended for patients with limited-disease small-cell lung cancer (LD-SCLC) who achieved good response to definitive chemoradiotherapy. However, most clinical studies lacked brain imaging scans before PCI. Our study aimed to investigate whether PCI has a survival benefit in patients who have no brain metastases (BM) confirmed via magnetic resonance imaging (MRI) before PCI. Results Eighty patients were included in this study. Sixty patients received PCI (PCI group) and 20 patients did not (non-PCI group). OS was not significantly different between the two groups. The median OS time was 4.3 years (95% CI: 2.6 years–8.6 years) in the PCI group and was not reached (NR) (95% CI: 1.9 years–NR) in the non-PCI group (p = 0.542). Moreover, no differences were observed in the 3-year rates of PFS (46.2% and 44.4%, p = 0.720) and cumulative incidence of BM (24.0% vs. 27%, p = 0.404). Conclusions Our result suggests that PCI may not have a survival benefit in patients with LD-SCLC confirmed to have no BM after initial therapy, even if patients achieve a good response to definitive chemoradiotherapy. Patients and Methods We retrospectively evaluated patients with LD-SCLC who were confirmed to have no BM via MRI after initial chemoradiotherapy at the Shizuoka Cancer Center between September 2002 and August 2015. The overall survival (OS), progression-free survival (PFS), and cumulative incidence of BM were estimated using the Kaplan–Meier method between patients who received PCI and those who did not. Propensity score matching was used to balance baseline characteristics. PMID:29707139

A Neuro-oncologist's Perspective on Management of Brain Metastases in Patients with EGFR Mutant Non-small Cell Lung Cancer.

Science.gov (United States)

McGranahan, Tresa; Nagpal, Seema

2017-04-01

Management of non-small cell lung cancer (NSCLC) with brain metastasis (BrM) has been revolutionized by identification of molecular subsets that have targetable oncogenes. Historically, survival for NSCLC with symptomatic BrM was weeks to months. Now, many patients are surviving years with limited data to guide treatment decisions. Tumors with activating mutations in epidermal growth factor receptor (EGFRact+) have a higher incidence of BrM, but a longer overall survival. The high response rate of both systemic and BrM EGFRact+ NSCLC to tyrosine kinase inhibitors (TKIs) has led to the rapid incorporation of new therapies but is outpacing evidence-based decisions for BrM in NSCLC. While whole brain radiation therapy (WBRT) was the foundation of management of BrM, extended survival raises concerns for the subacute and late effects radiotherapy. We favor the use of TKIs and delaying the use of WBRT when able. At inevitable disease progression, we consider alternative dosing schedules to increase CNS penetration (such as pulse dosing of erlotinib) or advance to next generation TKI if available. We utilize local control options of surgery or stereotactic radiosurgery (SRS) for symptomatic accessible lesions based on size and edema. At progression despite available TKIs, we use pemetrexed-based platinum doublet chemotherapy or immunotherapy if the tumor has high expression of PDL-1. We reserve the use of WBRT for patients with more than 10 BrM and progression despite TKI and conventional chemotherapy, if performance status is appropriate.

How to treat brain metastasis in 2012?

International Nuclear Information System (INIS)

Braccini, A.L.; Azria, D.; Mazeron, J.J.; Mornex, F.; Jacot, W.; Metellus, P.; Tallet, A.

2012-01-01

During the last French radiation oncology society annual congress, the therapeutic options for the management of brain metastases were presented. The indications and limits of surgery, stereotactic radiotherapy and whole brain radiotherapy, as well as their benefit in terms of overall survival, local control and improvement of the functional and neuro-cognitive status were discussed. The prognosis significance of the different phenotypes of breast cancer on the risk for BM as well as their roles in the treatment of brain metastases were also described. Surgery improves overall survival for patients with a single brain metastase and should be considered in the case of symptomatic lesions. The overall survival of patients treated with stereotactic radiotherapy do not differ from that of patients treated with surgery. These treatments should be mainly considered for patients with good performance status, one to three small brain metastases (< 3 cm) and limited extracranial disease. Whole brain radiotherapy is more and more discussed in adjuvant setting due to potential late neuro-cognitive toxicity. This toxicity could be improved with the development of techniques sparing the hippocampus. HER2+ and triple-negative breast cancer patients are at increased risk for brain metastases. Prognosis of these patients differs as the overall survival of HER2+ patients has improved with anti-HER2 therapies. The optimal combination of local and systemic therapies remain to be determined. (authors)

Metastasis of Pregnancy-Associated Breast Cancer (Suspected to Be Hereditary Breast and Ovarian Cancer to the Brain, Diagnosed at 18 Weeks’ Gestation: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Tomohiro Okuda

2016-01-01

Full Text Available We report a case of pregnancy-associated breast cancer with metastasis to the brain, likely resulting from hereditary breast and ovarian cancer (HBOC. A 35-year-old woman (gravida 2, para 0-1-0-1 underwent a right mastectomy and right axillary dissection after a cesarean section at 30 years of age; her mother died at 47 years of age due to breast cancer. Histopathological examination indicated an invasive ductal carcinoma with triple-negative cancer (cancer stage 2B [pT3N0M0]. The patient refused adjuvant therapy because of the risk of infertility. After 4 years, she became pregnant naturally. At 18 weeks’ gestation, she experienced aphasia and dyslexia due to brain metastasis. The pregnancy was terminated at 21 weeks’ gestation after thorough counseling. Her family history, young-onset disease, and histopathological findings suggested HBOC. She declined genetic testing for BRCA1/2, though genetic counseling was provided. In cases of pregnancy-related breast cancer, consideration must be given to whether the pregnancy should be continued and to posttreatment fertility. HBOC should also be considered. Genetic counseling should be provided and the patient should be checked for the BRCA mutation, as it is meaningful for the future of any potential children. Genetic counseling should be provided even if the cancer is advanced or recurrent.

Relationship Between HER2 Status and Prognosis in Women With Brain Metastases From Breast Cancer

International Nuclear Information System (INIS)

Xu Zhiyuan; Marko, Nicholas F.; Chao, Sam T.; Angelov, Lilyana; Vogelbaum, Michael A.; Suh, John H.; Barnett, Gene H.; Weil, Robert J.

2012-01-01

Purpose: To analyze factors affecting outcomes in breast cancer patients with brain metastases (BM) and characterize the role of HER2 status. Methods and Materials: We identified 264 breast cancer patients treated between 1999 and 2008 for BM. HER2 status was known definitively for 172 patients and was used to define cohorts in which survival and risk factors were analyzed. Results: Kaplan-Meier survival analysis demonstrated improved mean overall survival (105.7 vs. 74.3 months, p < 0.02), survival after diagnosis of BM (neurologic survival, NS) (32.2 vs. 18.9 months, p < 0.01), and survival after treatment with stereotactic radiosurgery (RS) (31.3 vs. 14.1, p < 0.01) in HER2+ patients relative to those with HER2− breast cancer. HER2+ status was an independent, positive prognostic factor for survival on univariate and multivariate hazard analysis (hazard ratio: overall survival = 0.66, 0.18; NS = 0.50, 0.34). Additionally, subgroup analysis suggests that stereotactic radiosurgery may be of particular benefit in patients with HER2+ tumors. Conclusions: Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2− lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2− and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions.

Using lithium as a neuroprotective agent in patients with cancer

Directory of Open Access Journals (Sweden)

Khasraw Mustafa

2012-11-01

Full Text Available Abstract Neurocognitive impairment is being increasingly recognized as an important issue in patients with cancer who develop cognitive difficulties either as part of direct or indirect involvement of the nervous system or as a consequence of either chemotherapy-related or radiotherapy-related complications. Brain radiotherapy in particular can lead to significant cognitive defects. Neurocognitive decline adversely affects quality of life, meaningful employment, and even simple daily activities. Neuroprotection may be a viable and realistic goal in preventing neurocognitive sequelae in these patients, especially in the setting of cranial irradiation. Lithium is an agent that has been in use for psychiatric disorders for decades, but recently there has been emerging evidence that it can have a neuroprotective effect. This review discusses neurocognitive impairment in patients with cancer and the potential for investigating the use of lithium as a neuroprotectant in such patients.

Brain tumors in patients primarly treated psychiatrically

Directory of Open Access Journals (Sweden)

Ignjatović-Ristić Dragana

2011-01-01

Full Text Available Introduction. Psychiatric symptoms are not rare manifestations of brain tumors. Brain tumors presented by symptoms of raised intracranial pressure, focal neurological signs, or convulsions are usually first seen by the neurologist or less frequently by the neurosurgeon in routine diagnostic procedures. On the other hand, when psychiatric symptoms are the first manifestation in “neurologically silent” brain tumors, the patients are sent to the psychiatrist for the treatment of psychiatric symptoms and brain tumors are left misdiagnosed for a long period of time. Case Report. We presented three patients with the diagnosed brain tumor where psychiatrist had been the first specialist to be consulted. In all three cases neurological examination was generally unremarkable with no focal signs or features of raised intracranial pressure. CT scan demonstrated right insular tumor in a female patient with obsessive-compulsive disorder (OCD; right parietal temporal tumor in a patient with delusions and depression and left frontal tumor in a patient with history of alcohol dependency. Conclusion. Psychiatric symptoms/disorders in patients with brain tumors are not specific enough and can have the same clinical presentation as the genuine psychiatric disorder. Therefore, we emphasize the consideration of neuroimaging in patients with abrupt beginning of psychiatric symptoms, in those with a change in mental status, or when headaches suddenly appear or in cases of treatment resistant psychiatric disorders regardless the lack of neurological symptoms.

Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

Science.gov (United States)

Thomas, Frédéric; Lafferty, Kevin D.; Brodeur, Jacques; Elguero, Eric; Gauthier-Clerc, Michel; Missé, Dorothée

2012-01-01

We explored associations between the common protozoan parasite Toxoplasma gondii and brain cancers in human populations. We predicted that T. gondii could increase the risk of brain cancer because it is a long-lived parasite that encysts in the brain, where it provokes inflammation and inhibits apoptosis. We used a medical geography approach based on the national incidence of brain cancers and seroprevalence of T. gondii. We corrected reports of incidence for national gross domestic product because wealth probably increases the ability to detect cancer. We also included gender, cell phone use and latitude as variables in our initial models. Prevalence of T. gondii explained 19 per cent of the residual variance in brain cancer incidence after controlling for the positive effects of gross domestic product and latitude among nations. Infection with T. gondii was associated with a 1.8-fold increase in the risk of brain cancers across the range of T. gondii prevalence in our dataset (4–67%). These results, though correlational, suggest that T. gondii should be investigated further as a possible oncogenic pathogen of humans.

Brain Metastases Treatment Worsens Cognitive Decline

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In some patients with cancer that has spread to the brain, whole brain radiation following radiosurgery causes more severe cognitive decline and does not improve survival compared with radiosurgery alone, a new study has found.

Predictors of quality of life and survival following Gamma Knife surgery for lung cancer brain metastases: a prospective study.

Science.gov (United States)

Bragstad, Sidsel; Flatebø, Marianne; Natvig, Gerd Karin; Eide, Geir Egil; Skeie, Geir Olve; Behbahani, Maziar; Pedersen, Paal-Henning; Enger, Per Øyvind; Skeie, Bente Sandvei

2017-08-18

OBJECTIVE Lung cancer (LC) patients who develop brain metastases (BMs) have a poor prognosis. Estimations of survival and risk of treatment-related deterioration in quality of life (QOL) are important when deciding on treatment. Although we know of several prognostic factors for LC patients with BMs, the role of QOL has not been established. Authors of this study set out to evaluate changes in QOL following Gamma Knife surgery (GKS) for BMs in LC patients and QOL as a prognostic factor for survival. METHODS Forty-four of 48 consecutive LC patients with BMs underwent GKS in the period from May 2010 to September 2011, and their QOL was prospectively assessed before and 1, 3, 6, 9, and 12 months after GKS by using the Functional Assessment of Cancer Therapy-Brain (FACT-BR) questionnaire. A mixed linear regression model was used to identify potential predictive factors for QOL and to assess the effect of GKS and the disease course on QOL at follow-up. RESULTS Mean QOL as measured by the brain cancer subscale (BRCS) of the FACT-BR remained stable from baseline (score 53.0) up to 12 months post-GKS (57.1; p = 0.624). The BRCS score improved for 32 patients (72.3%) with a total BM volume ≤ 5 cm 3 . Mean improvement in these patients was 0.45 points each month of follow-up, compared to a decline of 0.50 points each month despite GKS treatment in patients with BM volumes > 5 cm 3 (p = 0.04). Asymptomatic BMs (p = 0.01), a lower recursive partitioning analysis (RPA) classification (p = 0.04), and a higher Karnofsky Performance Scale (KPS) score (p Knife surgery is a safe and effective therapeutic modality that improves QOL for LC patients with a BM volume ≤ 5 cm 3 at treatment. Careful follow-up and salvage therapy on demand seem to prevent worsening of QOL due to relapse of BMs.

SFRO booklets - The radiotherapy of cancers: of anal canal (Anus), brain, mediastinum, pancreas, lung, prostate, rectum, breast, upper aero-digestive tract (ENT cancers), cervix, endometrium (cervical cancers), and bladder for a better understanding of radiotherapy, sarcoma radiotherapy - To better understand your treatment

International Nuclear Information System (INIS)

Leroy, Thomas; Mornex, Francoise; Peiffert, Didier; Thariat, Juliette; Faivre, Jean-Christophe; Huguet, Florence; Vendrely, Veronique; Barillot, Isabelle; Janoray, Guillaume; Bibault, Jean-Emmanuel; Antoni, Delphine; Crehange, Gilles; Meillan, Nicolas; Pichon, Baptiste; Biau, Julian; Pointreau, Yoann; Mirabel, Xavier; Leysalle, Axel; Claren, Audrey; Cartier, Lysian; Chand, Mari-Eve; Jacob, Julian; Renard-Oldrini, Sophie; Le Pechoux, Cecile; Ducassou, Anne; Moureau-Zabotto, Laurence; Lagrange, Jean Leon; Molina, Sarah

2016-07-01

This document gathers several booklets which, for different types of cancers, propose information regarding the anatomy and location of the cancer, its diagnosis, possible treatments, secondary effects during treatment, some practical advices, issues related to the post-treatment period, associations and other resources which can be useful for patient information, and a glossary of the main terms used for this cancer and its treatment. Cancer types are anal canal (Anus), brain, mediastinum, pancreas, lung, prostate, rectum, breast, upper aero-digestive tract (ENT cancers), cervix, endometrium (cervical cancers), and bladder cancers

Reference Data for Standardized Quality of Life Questionnaires in Indian Patients with Brain Metastases from Non-small Cell Lung Cancer: Results from a Prospective Study.

Science.gov (United States)

Aggarwal, Jaiprakash; Chakraborty, Santam; Ghosh Laskar, Sarbani; Patil, Vijay M; Prabhash, Kumar; Bhattacharya, Atanu; Noronha, Vanita; Purandare, Nilendu C; Joshi, Amit; Mummudi, Naveen; Arora, Jitendra; Badhe, Rupali

2017-04-10

Reference data for European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaires do not include studies from the Indian subcontinent. The objective of the current study was to establish a reference dataset for Indian patients of non-small cell lung cancer (NSCLC) presenting with brain metastases (BM). One hundred forty patients with NSCLC with BM treated between 2012-2015 were registered in a prospective cohort study (CTRI/2013/01/003299). The baseline quality of life was evaluated using the EORTC general quality of life questionnaire QLQ-C30 and lung cancer specific module LC13. Minimum important difference (MID) scores for individual domains of the EORTC QLQ-C30 and LC13 questionnaires were derived (MID = 0.2 x standard deviation) from the reference data for patients with recurrent/metastatic lung cancers. In addition, a systematic review was conducted to identify studies reporting baseline quality of life scores for recurrent/metastatic NSCLC. Scores of several functional as well as symptom scales in the current NSCLC population differed by more than the MID from the baseline mean scores in the reference EORTC population as well as that reported from other studies. Differences in mean score from the EORTC reference data ranged from 6.2 and 9.4 points for the role functioning and cognitive functioning domains. In the symptom scales, the largest differences were observed for the financial difficulties (23.9) scores for the QLQ-C30 and peripheral neuropathy (21.7) for LC13 questionnaires. The current study demonstrates that baseline reference scores need to be established for patients from the Indian subcontinent. The findings from the current study have important implications for studies employing quality of life (QOL) assessment in the Indian NSCLC patient population.

Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

OpenAIRE

Thomas, Frédéric; Lafferty, Kevin D.; Brodeur, Jacques; Elguero, Eric; Gauthier-Clerc, Michel; Missé, Dorothée

2011-01-01

We explored associations between the common protozoan parasite Toxoplasma gondii and brain cancers in human populations. We predicted that T. gondii could increase the risk of brain cancer because it is a long-lived parasite that encysts in the brain, where it provokes inflammation and inhibits apoptosis. We used a medical geography approach based on the national incidence of brain cancers and seroprevalence of T. gondii. We corrected reports of incidence for national gross domestic product b...

Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

NARCIS (Netherlands)

A. Niwińska (Anna); W. Olszewski (Wojciech); M. Murawska (Magdalena); K. Pogoda (Katarzyna)

2011-01-01

textabstractThe aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive

The brain stem function in patients with brain bladder

International Nuclear Information System (INIS)

Takahashi, Toshihiro

1990-01-01

A syndrome of detrusor-sphincter dyssynergia (DSD) is occasionally found in patients with brain bladder. To evaluate the brain stem function in cases of brain bladder, urodynamic study, dynamic CT scan of the brain stem (DCT) and auditory brainstem response (ABR) were performed. The region of interest of DCT aimed at the posterolateral portion of the pons. The results were analysed in contrast with the presense of DSD in urodynamic study. DCT studies were performed in 13 cases with various brain diseases and 5 control cases without neurological diseases. Abnormal patterns of the time-density curve consisted of low peak value, prolongation of filling time and low rapid washout ratio (low clearance ratio) of the contrast medium. Four of 6 cases with DSD showed at least one of the abnormal patterns of the time-density curve bilaterally. In 7 cases without DSD none showed bilateral abnormality of the curve and in 2 of 7 cases only unilateral abnormality was found. ABR was performed in 8 patients with brain diseases. The interpeak latency of the wave I-V (I-V IPL) was considered to be prolonged in 2 cases with DSD compared to that of 4 without DSD. In 2 cases with DSD who had normal DCT findings, measurement of the I-V IPL was impossible due to abnormal pattern of the ABR wave. Above mentioned results suggests the presence of functional disturbance at the posterolateral portion of the pons in cases of brain bladder with DSD. (author)

Risk factors for local failure requiring salvage neurosurgery after radiosurgery for brain metastases

International Nuclear Information System (INIS)

Weltman, Eduardo; Hanriot, Rodrigo de Morais; Prisco, Flavio Eduardo; Nadalin, Wladimir; Brandt, Reynaldo Andre; Moreira, Frederico Rafael

2004-01-01

Objective: the aim of this study is to select the risk factors for local failure requiring salvage neurosurgery in patients with brain metastases treated with stereotactic radiosurgery in a single institution. Methods: the follow-up of 123 patients, with 255 brain metastases treated with radiosurgery at the Radiation Oncology Department of the Hospital Israelita Albert Einstein from July 1993 to August 2001, was retrospectively analyzed. The criteria for salvage neurosurgery were tumor volume enlargement, or tumor persistence leading to severe neurological symptoms, life threatening situation or critical steroid dependence. We considered the case as local failure when the histopathologic evaluation showed morphologically preserved cancer cells (tumor recurrence, persistence or progression). We applied the Fisher's exact test to evaluate the statistical correlation between local failure and primary tumor histology, volume of the brain metastases, prescribed radiosurgery dose, and whole brain radiotherapy. Results: fourteen of 123 patients (11%) underwent salvage neurosurgery. Histology showed preserved cancer cells with necrosis and/or bleeding in 11 cases (9% of the total accrual), and only necrosis with or without bleeding (without preserved cancer cells) in three cases. The primary tumor histology among the 11 patients considered with active neoplasia was malignant melanoma in five cases (21% of the patients with melanoma), breast adenocarcinoma in three (16% of the patients with breast cancer), and other histology in the remaining three. Breast cancer diagnosis, non-elective whole brain irradiation, volume of the brain metastases, and the prescribed radiosurgery dose did not correlate with the risk of local failure. Patients treated with elective whole brain radiotherapy showed fewer local failures, when compared to all patients receiving whole brain radiotherapy, and to the patients not receiving this treatment, with incidence of failure in 4%,7% and 14

Role of infectious agents in the carcinogenesis of brain and head and neck cancers

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Alibek Kenneth

2013-02-01

Full Text Available Abstract This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV in distinct types of brain tumour, namely glioblastoma multiforme (GBM and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV and nasopharyngeal carcinoma (NPC. Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV and head and neck squamous cell carcinoma (HNSCC; specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90% and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of

Is admittance to specialised palliative care among cancer patients related to sex, age and cancer diagnosis? A nation-wide study from the Danish Palliative Care Database (DPD)

DEFF Research Database (Denmark)

Adsersen, Mathilde; Thygesen, Lau Caspar; Jensen, Anders Bonde

2017-01-01

/units. Patients with brain cancer were more often admitted to hospices, whereas patients with prostate cancer were more often admitted to hospital-based palliative care teams/units. CONCLUSION: It is unlikely that the variations in relation to sex, age and cancer diagnoses can be fully explained by differences...... to investigate whether cancer patients' admittance to SPC in Denmark varied in relation to sex, age and diagnosis, and whether the patterns differed by type of institution (hospital-based palliative care team/unit, hospice, or both). METHODS: This was a register-based study of adult patients living in Denmark......BACKGROUND: Specialised palliative care (SPC) takes place in specialised services for patients with complex symptoms and problems. Little is known about what determines the admission of patients to SPC and whether there are differences in relation to institution type. The aims of the study were...

Survival prediction using temporal muscle thickness measurements on cranial magnetic resonance images in patients with newly diagnosed brain metastases

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Furtner, Julia; Prayer, Daniela [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Berghoff, Anna S.; Zielinski, Christoph C.; Preusser, Matthias [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Albtoush, Omar M. [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); University of Jordan, Department of Radiology and Nuclear Medicine, Amman (Jordan); Woitek, Ramona; Asenbaum, Ulrika [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Widhalm, Georg; Gatterbauer, Brigitte [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Dieckmann, Karin [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Radiotherapy, Vienna (Austria); Birner, Peter [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Medical University of Vienna, Department of Pathology, Vienna (Austria); Aretin, Bernadette [General Hospital Vienna, Pharmacy Department, Vienna (Austria); Bartsch, Rupert [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumor Unit (CCC-CNS), Vienna (Austria); Schoepf, Veronika [University of Graz, Institute of Psychology, Graz (Austria); BioTechMed, Graz (Austria)

2017-08-15

To evaluate the prognostic relevance of temporal muscle thickness (TMT) in brain metastasis patients. We retrospectively analysed TMT on magnetic resonance (MR) images at diagnosis of brain metastasis in two independent cohorts of 188 breast cancer (BC) and 247 non-small cell lung cancer (NSCLC) patients (overall: 435 patients). Survival analysis using a Cox regression model showed a reduced risk of death by 19% with every additional millimetre of baseline TMT in the BC cohort and by 24% in the NSCLC cohort. Multivariate analysis included TMT and diagnosis-specific graded prognostic assessment (DS-GPA) as covariates in the BC cohort (TMT: HR 0.791/CI [0.703-0.889]/p < 0.001; DS-GPA: HR 1.433/CI [1.160-1.771]/p = 0.001), and TMT, gender and DS-GPA in the NSCLC cohort (TMT: HR 0.710/CI [0.646-0.780]/p < 0.001; gender: HR 0.516/CI [0.387-0.687]/p < 0.001; DS-GPA: HR 1.205/CI [1.018-1.426]/p = 0.030). TMT is easily and reproducibly assessable on routine MR images and is an independent predictor of survival in patients with newly diagnosed brain metastasis from BC and NSCLC. TMT may help to better define frail patient populations and thus facilitate patient selection for therapeutic measures or clinical trials. Further prospective studies are needed to correlate TMT with other clinical frailty parameters of patients. (orig.)

Survival prediction using temporal muscle thickness measurements on cranial magnetic resonance images in patients with newly diagnosed brain metastases

International Nuclear Information System (INIS)

Furtner, Julia; Prayer, Daniela; Berghoff, Anna S.; Zielinski, Christoph C.; Preusser, Matthias; Albtoush, Omar M.; Woitek, Ramona; Asenbaum, Ulrika; Widhalm, Georg; Gatterbauer, Brigitte; Dieckmann, Karin; Birner, Peter; Aretin, Bernadette; Bartsch, Rupert; Schoepf, Veronika

2017-01-01

To evaluate the prognostic relevance of temporal muscle thickness (TMT) in brain metastasis patients. We retrospectively analysed TMT on magnetic resonance (MR) images at diagnosis of brain metastasis in two independent cohorts of 188 breast cancer (BC) and 247 non-small cell lung cancer (NSCLC) patients (overall: 435 patients). Survival analysis using a Cox regression model showed a reduced risk of death by 19% with every additional millimetre of baseline TMT in the BC cohort and by 24% in the NSCLC cohort. Multivariate analysis included TMT and diagnosis-specific graded prognostic assessment (DS-GPA) as covariates in the BC cohort (TMT: HR 0.791/CI [0.703-0.889]/p < 0.001; DS-GPA: HR 1.433/CI [1.160-1.771]/p = 0.001), and TMT, gender and DS-GPA in the NSCLC cohort (TMT: HR 0.710/CI [0.646-0.780]/p < 0.001; gender: HR 0.516/CI [0.387-0.687]/p < 0.001; DS-GPA: HR 1.205/CI [1.018-1.426]/p = 0.030). TMT is easily and reproducibly assessable on routine MR images and is an independent predictor of survival in patients with newly diagnosed brain metastasis from BC and NSCLC. TMT may help to better define frail patient populations and thus facilitate patient selection for therapeutic measures or clinical trials. Further prospective studies are needed to correlate TMT with other clinical frailty parameters of patients. (orig.)

Re-irradiation for metastatic brain tumors with whole-brain radiotherapy

International Nuclear Information System (INIS)

Akiba, Takeshi; Kunieda, Etsuo; Kogawa, Asuka; Komatsu, Tetsuya; Tamai, Yoshifumi; Ohizumi, Yukio

2012-01-01

The objective of this study was to determine whether second whole-brain irradiation is beneficial for patients previously treated with whole-brain irradiation. A retrospective analysis was done for 31 patients with brain metastases who had undergone re-irradiation. Initial whole-brain irradiation was performed with 30 Gy/10 fractions for 87% of these patients. Whole-brain re-irradiation was performed with 30 Gy/10 fractions for 42% of these patients (3-40 Gy/1-20 fractions). Three patients underwent a third whole-brain irradiation. The median interval between the initial irradiation and re-irradiation was 10 months (range: 2-69 months). The median survival time after re-irradiation was 4 months (range: 1-21 months). The symptomatic improvement rate after re-irradiation was 68%, and the partial and complete tumor response rate was 55%. Fifty-two percent of the patients developed Grade 1 acute reactions. On magnetic resonance imaging, brain atrophy was observed in 36% of these patients after the initial irradiation and 74% after re-irradiation. Grade ≥2 encephalopathy or cognitive disturbance was observed in 10 patients (32%) after re-irradiation. Based on univariate analysis, significant factors related to survival after re-irradiation were the location of the primary cancer (P=0.003) and the Karnofsky performance status at the time of re-irradiation (P=0.008). A Karnofsky performance status ≥70 was significant based on multivariate analysis (P=0.050). Whole-brain re-irradiation for brain metastases placed only a slight burden on patients and was effective for symptomatic improvement. However, their remaining survival time was limited and the incidence of cognitive disturbance was rather high. (author)

Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

DEFF Research Database (Denmark)

Zukauskaite, Ruta; Schmidt, Henrik; Asmussen, Jon T

2013-01-01

-enhanced CT scan of the brain before the start of interleukin-2 (IL-2)-based immunotherapy. Among the 697 patients, 80 had asymptomatic brain metastases (12%). Patients' characteristics did not differ significantly between groups with and without brain metastases. Patients received systemic treatment (IL-2......The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast......-based or cytotoxic chemotherapy), local treatment (stereotactic radiotherapy, whole-brain radiotherapy or surgery), or best supportive care only. The survival was significantly shorter for patients with asymptomatic brain metastases compared with patients without brain metastases (P...

Current status of sperm banking for young cancer patients in Japanese nationwide survey.

Science.gov (United States)

Yumura, Yasushi; Tsujimura, Akira; Okada, Hiroshi; Ota, Kuniaki; Kitazawa, Masahumi; Suzuki, Tatsuya; Kakinuma, Tosiyuki; Takae, Seido; Suzuki, Nao; Iwamoto, Teruaki

2018-02-02

This study aimed to ascertain the current status of Japanese sperm banking for young cancer patients. During 2015, we mailed the directors of 695 institutes where sperm cryopreservation might be performed with questionnaires requesting information on the number of patients, age, precryopreservation chemotherapy, semen analyses results and diagnoses, cryopreservation success rate, and causes of unsuccessful cryopreservation. Of these 695 institutes, 92 had cryopreserved sperm before chemotherapy within the study period. In all, 820 cancer patients (237 testicular, 383 hematological, 46 bone and soft tissue, 20 brain, and 134 other malignancy) consulted the responding institutes for sperm cryopreservation. Except for testicular tumor, the number of patients whose sperm was preserved before cancer treatment was low compared to that of young cancer patients. Approximately 20% of patients with malignancies other than testicular tumor underwent chemotherapy before cryopreservation. The success rate of cryopreservation in hematological malignancy was 82.5%, significantly lower than that of both the testicular cancer (93.6%) and other malignancy groups (95.6%) (P < 0.05). The primary reasons for preservation failure were azoospermia and poor semen quality. Patients with hematological malignancies had a higher rate of unsuccessful cryopreservation compared to those in other groups, possibly due to the large number of patients requesting sperm cryopreservation after chemotherapy induction. In Japan, information regarding sperm banking prior to cancer treatment appears to be lacking. Information regarding sperm preservation before chemotherapy should be provided to all Japanese oncologists.

Prophylactic Anticonvulsants in patients with brain tumour

International Nuclear Information System (INIS)

Forsyth, P.A.; Weaver, S.; Fulton, D.

2003-01-01

We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13 -30.1 months). Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p=0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p=0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need ≥900 patients to have a suitably powered study. These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure. (author)

Prophylactic Anticonvulsants in patients with brain tumour

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Forsyth, P.A. [Depts. of Oncology and Clinical Neurosciences, Univ. of Calgary, Calgary, Alberta (Canada); Tom Baker Cancer Centre, Calgary, Alberta (Canada); Weaver, S. [Depts. of Neurology and Medicine, Albany Medical College, Albany, New York (United States); Fulton, D. [Dept. of Radiation Oncology, Cross Cancer Institute and Dept. of Medicine/Neurology, Univ. of Alberta, Edmonton, Alberta (Canada)

2003-05-01

We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis. One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13 -30.1 months). Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p=0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p=0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need {>=}900 patients to have a suitably powered study. These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure. (author)

EG-17SUV420-MEDIATED HETEROCHROMATIN CHANGES IN PEDIATRIC BRAIN CANCERS

Science.gov (United States)

Van Meter, Timothy E.; Terry, Jocelyn; Rockwell, Nathan; Goggin, Sarah; Nethala, Priya; Khan, Asadullah

2014-01-01

Silencing mechanisms play a role in genomic stability by maintaining condensed, non-active regions of the genome. SUV420 enzymes contain a SET domain conferring methyltransferase activity toward histones. The Histone H4 lysine 20 trimethylation (H4K20me3) mark maintained by SUV420H2 is associated with heterochromatin formation and gene silencing, whereas the dimethylated mark (H4K20me2) is associated with DNA repair. In studies of epigenetic factors in large patient cohorts with ependymoma, it was found that SUV420H2 expression was lost or diminished in patients with reciprocal increases in prognostic markers such as hTERT. To better understand the normal function of Suv4-20H1/H2 enzyme in neural progenitors, and pathological changes in cancers, a variety of differentiation paradigms were used. The NT2D1 neurally restricted cell line, and BGO1V and H9 human embryonic stem cells (ESCs), and differentiated progeny, were used alongside tumors to better understand enzyme targets and functional outcomes (e.g.,lineage, differentiation, regional chromatin modifications). Lineage stages were verified with stage-specific markers by immunofluorescence and qPCR. Suv4-20 H1 and H2 were present in ESCs and neural progenitors and decreased thereafter. RNAi knockdown of SUV420 enzymes led to decreased H4K20 methylation in cancer cells. DNA methylation microarrays and ChIP-PCR suggest 1) that SUV420 is not regulated by DNA methylation in ependymomas; 2) that active chromatin marks such as H3K4 dimethylation are enriched near the transcriptional start site in the SUV420H2 gene, and 3) that hTERT is hyper-methylated at specific CpG islands and histones in a tumor sub-group-specific manner. This data supports the hypothesis that Suv4-20H2 is highly active in progenitor cells and functionally lost in some brain cancers. These studies begin to elucidate coincident mechanisms of gene silencing active in neural progenitors that may be altered in a subset of pediatric brain cancers.

Analysis of outcome in patients reirradiated for brain metastases

International Nuclear Information System (INIS)

Wong, William W.; Schild, Steven E.; Sawyer, Timothy E.; Shaw, Edward G.

1995-01-01

Purpose: Patients with brain metastases generally benefit from whole brain irradiation (WBRT). However, the role of reirradiation for patients who develop progressive brain metastases after a course of WBRT has been controversial. This retrospective study examines our experience with reirradiation of patients for progressive brain metastases after an initial course of WBRT. Materials and Methods: From 1975 to 1993, 2658 patients received WBRT for brain metastases at our institutions. Eighty-six patients were subsequently reirradiated for progressive brain metastases. The median age of these patients was 58 (range: 31-81). The primary sites included breast (31 patients), lung (31 patients), colon (6 patients), melanoma (5 patients), and others (13 patients). Fifty patients had metastatic disease at other sites. Most patients had ECOG performance status of 2 (39 patients) or 3 (36 patients). The median dose of the first course of irradiation was 30 Gy (range: 20-50.4 Gy). The median time interval between the first and second courses of irradiation was 7.6 months (range: 1.5-50.6 months). The median dose of the second course of irradiation was 20 Gy (range: 8.0 to 30.6 Gy). All except one patients were given steroids. Patients were followed until death, except for one patient who was lost to follow-up and one long-term surviver who was followed for 72 months. Results: Twenty-three patients (27%) had complete resolution of neurologic symptoms, 37 patients (43%) had partial improvement of neurologic symptoms, and 24 patients (28%) had either no subjective response or worsened after reirradiation. The RTOG neurological function class improved in 32 patients, remained unchanged in 40 patients, and deteriorated in 8 patients. Survival following reirradiation ranged from 0.25 to 72 months with a median survival of 4 months. The majority of patients had no toxicity secondary to reirradiation. Five patients had radiographic abnormalities of their brains consistent with

Depression in Cancer Patients

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Beyhan Bag

2014-06-01

Full Text Available It is not enough to consider treatment and care depression in the oncology that is the most common psychiatric illness in cancer patient affects of cancer treatment and the patient`s quality of life negatively, which is determined through researches in the field. With development of psycho-oncology it has been demonstrated to establish an important link between the cancer patient`s treatment as well as psycho-social support for the patient and psychiatric treatment and care for the if it is needed. With this connection between them it has been proposed to use of bio-psycho-social-model in cancer patient to improve their care. To achieve this goal, it is expected from medical personnel to realize patients psychosocial need und if he/she has a psychiatric disorders or syndromes. For the medical personnel that work in oncology services, it is inevitable to organize in order to raise the awareness of depression in the cancer patients. In the present study, it is focused on raising the awareness of depression in cancer patient for the medical personnel. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(2.000: 186-198

Pathologic Characteristics and Treatment Outcome of Patients with Malignant Brain Tumors: A Single Institutional Experience from Iran

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Abdolazim Sedighi Pashaki

2014-03-01

Full Text Available Background: Central nervous system tumors account for 2%-5% of all malignancies in humans. These tumors account for 2% of all pediatric cancers. The worldwide incidence of primary central nervous system tumors is estimated at 3.9 (males and 3.2 (females per 100000 person-years. The incidence of brain tumor cases has been reported as 3.67% of all malignancies and 4% of all cancer mortalities in Iran. The five most common histological types of brain tumor in Iran according to different case studies are; meningioma, astrocytoma, glioblastoma, pituitary adenoma and ependymoma. The aim of this study is to determine the histopathological pattern and characteristics of patients with brain tumors who have referred to the Mahdieh Radiotherapy Department, Hamadan, Iran. Methods: This descriptive, retrospective study was performed at the Mahdieh Radiotherapy Department, between 2005 and 2012. We included 220 patients who referred to the Radiotherapy Department with diagnoses of primary brain tumor in this study. Results: Between 2005 and 2012, we treated 220 new cases of primary brain tumor at Mahdieh Radiotherapy Department. The mean age at diagnosis was 39.95±15.48 years with a median age of 39 years. Patients' ages ranged from 4 to 75 years. Among the 220 patients, 138 were male and 82 were female with a male to female ratio of 1.68. For most tumors there was a male predominance, with the exception of meningioma (M/F: 0.23, ependymoma (M/F: 1 and pituitary adenoma (M/F: 0.6. Astrocytomas, glioblastomas, high grade meningiomas and oligodendrogliomas were the four most common pathologies treated in this department. The best treatment results were achieved in patients with astrocytomas. Conclusion: The present study is a retrospective radiotherapy centre-based study designed in a pioneer radiotherapy centre in Western Iran, not a prospective population study. These data have provided a baseline for further epidemiological studies. Our encouraging results

Cognition and brain abnormalities on MRI in pituitary patients

International Nuclear Information System (INIS)

Brummelman, Pauline; Sattler, Margriet G.A.; Meiners, Linda C.; Berg, Gerrit van den; Klauw, Melanie M. van der; Elderson, Martin F.; Dullaart, Robin P.F.; Koerts, Janneke; Werumeus Buning, Jorien; Tucha, Oliver; Wolffenbuttel, Bruce H.R.; Bergh, Alfons C.M. van den; Beek, André P. van

2015-01-01

Highlights: • Cognitive impairments are frequently observed in treated NFA patients. • NFA patients with cognitive impairments do not show brain abnormalities on MRI more frequently than patients without cognitive impairments. • The absence of brain abnormalities on brain MRI does not exclude impairments of cognition. - Abstract: Purpose: The extent to which cognitive dysfunction is related to specific brain abnormalities in patients treated for pituitary macroadenoma is unclear. Therefore, we compared brain abnormalities seen on Magnetic Resonance Imaging (MRI) in patients treated for nonfunctioning pituitary macroadenoma (NFA) with or without impairments in cognitive functioning. Methods: In this cross-sectional design, a cohort of 43 NFA patients was studied at the University Medical Center Groningen. White matter lesions (WMLs), cerebral atrophy, (silent) brain infarcts and abnormalities of the temporal lobes and hippocampi were assessed on pre-treatment and post-treatment MRI scans. Post-treatment cognitive examinations were performed using a verbal memory and executive functioning test. We compared our patient cohort with large reference populations representative of the Dutch population. Results: One or more impairments on both cognitive tests were frequently observed in treated NFA patients. No treatment effects were found with regard to the comparison between patients with and without impairments in executive functioning. Interestingly, in patients with one or more impairments on verbal memory function, treatment with radiotherapy had been given more frequently (74% in the impaired group versus 40% in the unimpaired group, P = 0.025). Patients with or without any brain abnormality on MRI did not differ in verbal memory or executive functioning. Conclusions: Brain abnormalities on MRI are not observed more frequently in treated NFA patients with impairments compared to NFA patients without impairments in verbal memory or executive functioning

Cognition and brain abnormalities on MRI in pituitary patients

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Brummelman, Pauline [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Sattler, Margriet G.A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen (Netherlands); Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Meiners, Linda C. [Department of Radiology, University of Groningen, University Medical Center Groningen (Netherlands); Berg, Gerrit van den; Klauw, Melanie M. van der [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Elderson, Martin F. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); LifeLines Cohort Study and Biobank, University of Groningen, University Medical Center Groningen (Netherlands); Dullaart, Robin P.F. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Koerts, Janneke [Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen (Netherlands); Werumeus Buning, Jorien, E-mail: j.werumeus.buning@umcg.nl [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Tucha, Oliver [Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen (Netherlands); Wolffenbuttel, Bruce H.R. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); LifeLines Cohort Study and Biobank, University of Groningen, University Medical Center Groningen (Netherlands); Bergh, Alfons C.M. van den [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen (Netherlands); Beek, André P. van, E-mail: a.p.van.beek@umcg.nl [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands)

2015-02-15

Highlights: • Cognitive impairments are frequently observed in treated NFA patients. • NFA patients with cognitive impairments do not show brain abnormalities on MRI more frequently than patients without cognitive impairments. • The absence of brain abnormalities on brain MRI does not exclude impairments of cognition. - Abstract: Purpose: The extent to which cognitive dysfunction is related to specific brain abnormalities in patients treated for pituitary macroadenoma is unclear. Therefore, we compared brain abnormalities seen on Magnetic Resonance Imaging (MRI) in patients treated for nonfunctioning pituitary macroadenoma (NFA) with or without impairments in cognitive functioning. Methods: In this cross-sectional design, a cohort of 43 NFA patients was studied at the University Medical Center Groningen. White matter lesions (WMLs), cerebral atrophy, (silent) brain infarcts and abnormalities of the temporal lobes and hippocampi were assessed on pre-treatment and post-treatment MRI scans. Post-treatment cognitive examinations were performed using a verbal memory and executive functioning test. We compared our patient cohort with large reference populations representative of the Dutch population. Results: One or more impairments on both cognitive tests were frequently observed in treated NFA patients. No treatment effects were found with regard to the comparison between patients with and without impairments in executive functioning. Interestingly, in patients with one or more impairments on verbal memory function, treatment with radiotherapy had been given more frequently (74% in the impaired group versus 40% in the unimpaired group, P = 0.025). Patients with or without any brain abnormality on MRI did not differ in verbal memory or executive functioning. Conclusions: Brain abnormalities on MRI are not observed more frequently in treated NFA patients with impairments compared to NFA patients without impairments in verbal memory or executive functioning

Analysis of outcome in patients reirradiated for brain metastases

International Nuclear Information System (INIS)

Wong, William W.; Schild, Steven E.; Sawyer, Timothy E.; Shaw, Edward G.

1996-01-01

Purpose: Patients with newly diagnosed brain metastases generally benefit from whole brain radiation therapy (WBRT). However, the role of reirradiation for patients who develop progressive brain metastases has been controversial. This retrospective study examines our experience with reirradiation of patients for progressive brain metastases after an initial course of WBRT. Methods and Materials: From 1975-1993, 2658 patients received WBRT for brain metastases at our institution. Eighty-six patients were subsequently reirradiated for progressive brain metastases. The median age of these patients was 58 (range: 31-81). The most common primary sites were breast and lung. Fifty patients had metastatic disease at other sites. Most patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 (40 patients) or 3 (38 patients). The median dose of the first course of irradiation was 30 Gy (range: 1.5-50.6 Gy). The median dose of the second course of irradiation was 20 Gy (range: 8.0-30.6 Gy). Results: Twenty-three patients (27%) had resolution of neurologic symptoms, 37 patients (43%) had partial improvement of neurologic symptoms, and 25 patients (29%) had either no change or worsened after reirradiation. The median survival following reirradiation was 4 months (range: 0.25-72 months). The majority of patients had no significant toxicity secondary to reirradiation. Five patients had radiographic abnormalities of their brain consistent with radiation-related changes. One patient had symptoms of dementia that was thought to be caused by radiotherapy. Various potential prognostic factors were evaluated for possible associations with survival, including age, sex, primary site, ECOG performance status, RTOG neurologic functional class, absence of extracranial metastases, number of brain metastases, and dose of reirradiation. Absence of extracranial metastasis, solitary brain metastasis, and a retreatment dose > 20 Gy were associated with improved survival in

Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet

Directory of Open Access Journals (Sweden)

Seyfried B

2009-09-01

Full Text Available Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect, malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.

Stereotactic radiosurgery improves the survival in patients with solitary brain metastasis: a reasonable alternative to surgery

International Nuclear Information System (INIS)

Kwan, H. Cho; Hall, Walter A.; Lee, Andrew K.; Gerbi, Bruce J.; Higgins, Patrick D.; Nussbaum, Eric S.; Chung, K.K. Lee; Bohen, Marva; Clark, H. Brent

1996-01-01

Purpose: To evaluate the efficacy of stereotactic radiosurgery (SRS) in patients with solitary brain metastasis from extracranial primary cancer and to compare the outcome with that of external whole brain irradiation with or without surgical resection. Materials and Methods: Between September 1970 and November, 1995, 231 patients with solitary brain metastasis were treated at the Department of Radiation Oncology, University of Minnesota Hospital. One hundred twenty six patients (56%) were treated with external whole brain irradiation (WBI) only (Group 1), seventy three (32%) underwent surgical resection prior to WBI (Group 2) and thirty two (14%) underwent stereotactic radiosurgery (SRS) with WBI (Group 3). Lung (38%) was the most common site of primary cancer, followed by breast (15%), unknown primary (12%), gastro-intestinal tract (10%), skin (malignant melanoma: 9%), kidney (renal cell carcinoma: 8%) and others (9%). The median dose to the whole brain was 3750 cGy in 15 fractions (ranges from 2000 cGy to 5000 cGy). The median radiosurgical dose of 17.5 Gy (range, 12-40 Gy) was delivered to the 40%-90% isodose line encompassing the target. Eighteen patients were treated with SRS for recurrent or persistent disease following WBI and 14 patients received SRS as a boost in conjunction with WBI. Actuarial survival was calculated from the date of treatment according to the Kaplan-Meier method and statistical significance was assessed with the log-rank test. Results: The actuarial median survivals were 3.8 months for Group 1 (ranges from 1 to 84 months), 10.5 months for Group 2 (ranges from 1 to 125 months) and 9.8 months for Group 3 (ranges from 1 to 36 months). The survivals at one and two years were 19% and 6% for Group 1, 47% and 19% for Group 2, and 44% and 21% for Group 3, respectively. The survival advantage of Groups 2 or 3 over Group 1 was statistically significant (p < 0.0001 by log-rank test). There was no survival advantage of surgery (Group 2) over SRS

Diagnosis and treatment of brain metastasis

International Nuclear Information System (INIS)

Sajama, Carlos; Lorenzoni, Jose; Tagle, Patricio

2008-01-01

Cerebral metastasis occur in 20 to 30 percent of patients with systemic cancer and are the most common type of intracranial tumor. The median survival of untreated patients is one month with a slightly longer survival in those treated with steroids. Patients treated with whole brain radiation therapy survive between 3 to 6 months. In selected cases survival can increase to 10 to 12 months with combination of surgery and radiotherapy or stereotactic radiosurgery alone or associated to radiotherapy. Most brain metastasis arise from lung, breast and melanomas. The most important criteria for selecting patients who will benefit from surgery or stereotactic radiosurgery are a Karnofsky score of 70 or more, systemic control of the cancer and absence of leptomeningeal involvement. Surgery is indicated in patients with a single lesion located in an accessible zone and stereotactic radiosurgery is indicated for lesions up to 3 cm of diameter, and in patients with up to 3 or 4 metastasis, no matter their location. The survival benefit of chemotherapy in brain metastasis has not been demonstrated

Nanotech revolution for the anti-cancer drug delivery through blood-brain barrier.

Science.gov (United States)

Caraglia, M; De Rosa, G; Salzano, G; Santini, D; Lamberti, M; Sperlongano, P; Lombardi, A; Abbruzzese, A; Addeo, R

2012-03-01

Nanotechnology-based drug delivery was born as a chance for pharmaceutical weapons to be delivered in the body sites where drug action is required. Specifically, the incorporation of anti-cancer agents in nanodevices of 100-300 nm allows their delivery in tissues that have a fenestrated vasculature and a reduced lymphatic drainage. These two features are typical of neoplastic tissues and, therefore, allow the accumulation of nanostructured devices in tumours. An important issue of anti-cancer pharmacological strategies is the overcoming of anatomical barriers such as the bloodbrain- barrier (BBB) that protects brain from toxicological injuries but, at the same time, makes impossible for most of the pharmacological agents with anti-cancer activity to reach tumour cells placed in the brain and derived from either primary tumours or metastases. In fact, only highly lipophilic molecules can passively diffuse through BBB to reach central nervous system (CNS). Another possibility is to use nanotechnological approaches as powerful tools to across BBB, by both prolonging the plasma half-life of the drugs and crossing fenestrations of BBB damaged by brain metastases. Moreover, modifications of nanocarrier surface with specific endogenous or exogenous ligands can promote the crossing of intact BBB as in the case of primary brain tumours. This aim can be achieved through the binding of the nanodevices to carriers or receptors expressed by the endothelial cells of BBB and that can favour the internalization of the nanostructured devices delivering anti-cancer drugs. This review summarizes the most meaningful advances in the field of nanotechnologies for brain delivery of drugs.

Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

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Schild Steven E

2010-10-01

Full Text Available Abstract Background This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the radiation dose was investigated. Methods Data from 220 patients were retrospectively analyzed for overall survival and local control. Nine potential prognostic factors were evaluated: tumor type, WBI schedule, age, gender, Karnofsky performance score, number of brain metastases, extracerebral metastases, interval from diagnosis of cancer to WBI, and recursive partitioning analysis (RPA class. Results Survival rates at 6 and 12 months were 32% and 19%, respectively. In the multivariate analysis, WBI doses >30 Gy (p = 0.038, KPS ≥70 (p Conclusions Improved outcomes were associated with WBI doses >30 Gy, better performance status, fewer brain metastases, lack of extracerebral metastases, and lower RPA class. Patients receiving WBI alone appear to benefit from WBI doses >30 Gy. However, such a benefit is limited to RPA class 1 or 2 patients.

Characteristics of breast cancer patients with central nervous system metastases: a single-center experience.

Science.gov (United States)

Harputluoglu, Hakan; Dizdar, Omer; Aksoy, Sercan; Kilickap, Saadettin; Dede, Didem S; Ozisik, Yavuz; Guler, Nilufer; Barista, Ibrahim; Gullu, Ibrahim; Hayran, Mutlu; Selek, Ugur; Cengiz, Mustafa; Zorlu, Faruk; Tekuzman, Gulten; Altundag, Kadri

2008-05-01

The aim of this study was to assess the characteristics of breast cancer patients with central nervous system (CNS) metastases and factors associated with survival after development of CNS metastasis. One-hundred-forty-four patients with brain metastases were retrospectively analyzed. Median age at the time of brain metastasis diagnosis was 48.9. Median time between initial diagnosis and development of brain metastasis was 36 months. Fourteen cases had leptomeningeal involvement. Twenty-two patients (15.3%) had single metastasis. Ten percent of the patients had surgery, 94% had radiotherapy and 63% had chemotherapy. Median survival after development of brain metastasis was 7.4 months. Survival of patients with single metastasis was significantly longer than those with multiple metastases (33.5 vs. 6.5 months, p = 0.0006). Survival of patients who received chemotherapy was significantly longer than those who received radiotherapy alone (9.9 vs. 2 months, p < 0.0001). In multivariate Cox regression analyses, presence of single metastasis and application of chemotherapy were the only significant factors associated with better survival (p = 0.047 and p < 0.0001, respectively). Age at initial diagnosis or at the time of brain metastasis, time from initial diagnosis to development of brain metastasis, menopausal status, tumor stage, grade, hormone receptor or HER2 status individually were not associated with survival. In this study, survival after the diagnosis of CNS metastases appeared to be affected by patient characteristics rather than biologic characteristics of the tumor. This is probably secondary to the lack of effective treatment options in these patients and overall poor prognosis.

Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

NARCIS (Netherlands)

Meyners, T.; Heisterkamp, C.; Kueter, J.D.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.; Rades, D.

2010-01-01

Background: This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from

Assessment of brain phenylalanine dynamics in phenylketonuria patients

International Nuclear Information System (INIS)

Bik-Multanowski, M.; Pietrzyk, J. J.; Pasowicz, M.; Banys, R.P.

2006-01-01

Phenylketonuria (PKU) is the most common inborn error of metabolism in man. Brain phenylalanine kinetics can determine neurological treatment outcome in phenylketonuria. The aim of our study wa sto test a simplified magnetic resonance spectroscopy method for assessment of brain phenylalanine dynamics in PKU patients. Brain phenylalanine concentration (measured by means of magnetic resonance spectroscopy) and blood phenylalanine concentrations changes occurring within 24 hours after oral phenylalanine loading were analyzed in 5 PKU patients. The brain/blood phenylalanine ratio in 3 persons with normal intelligence was lower than in 2 with borderline intelligence or mild mental retardation. In our opinion the proposed method could be useful for assessment of brain phenylalanine dynamics in PKU patients. (author)

Brain Tumor Trials Collaborative | Center for Cancer Research

Science.gov (United States)

Brain Tumor Trials Collaborative In Pursuit of a Cure The mission of the BTTC is to develop and perform state-of-the-art clinical trials in a collaborative and collegial environment, advancing treatments for patients with brain tumors, merging good scientific method with concern for patient well-being and outcome.

Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome.

Science.gov (United States)

Abu-Judeh, H H; Levine, S; Kumar, M; el-Zeftawy, H; Naddaf, S; Lou, J Q; Abdel-Dayem, H M

1998-11-01

Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

A systematic review of trastuzumab and lapatinib in the treatment of women with brain metastases from HER2-positive breast cancer

DEFF Research Database (Denmark)

Larsen, Pia Bükmann; Kümler, Iben; Nielsen, Dorte Lisbet

2013-01-01

Patients with HER2-positive breast cancer are living still longer and increasingly experiencing brain metastases. Current HER2-targeted therapies have limited potential to cross the blood-brain-barrier. We performed a systematic review to investigate data on HER2-targeting therapies in the treatm......, it is still not evident which HER2-targeting agent should be preferred when brain metastases occur. The choice of chemotherapy to accompany the blockade is not obvious and we do not know if dual is better than single blockade. Further clinical trials are urgently needed....