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Sample records for cancer brain metastases

  1. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    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....

  2. 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)

  3. 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)

  4. Results of radiotherapy for brain metastases from lung cancer

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    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.

  5. Brain abscess mimicking lung cancer metastases; a case report.

    Science.gov (United States)

    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.

  6. 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

  7. Lung cancer brain metastases – the role of neurosurgery

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    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.

  8. 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.

  9. Radiological Patterns of Brain Metastases in Breast Cancer Patients : A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry

    NARCIS (Netherlands)

    Laakmann, Elena; Witzel, Isabell; Scriba, Verena; Grzyska, Ulrich; zu Eulenburg, Christine; Burchardi, Nicole; Hesse, Tobias; Wuerschmidt, Florian; Fehm, Tanja; Moebus, Volker; von Minckwitz, Gunter; Loibl, Sibylle; Park-Simon, Tjoung-Won; Mueller, Volkmar

    2016-01-01

    Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans of 300 breast cancer patients with brain

  10. Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC Registry

    Directory of Open Access Journals (Sweden)

    Elena Laakmann

    2016-09-01

    Full Text Available Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT and magnetic resonance imaging (MRI scans of 300 breast cancer patients with brain metastases (BMs were collected retrospectively in four centers participating in the Brain Metastases in Breast Cancer Registry (BMBC in Germany. Patients with positive estrogen (ER, progesterone (PR, or human epidermal growth factor receptor 2 (HER2 statuses, had a significantly lower number of BMs at diagnosis. Concerning the treatment mode, HER2-positive patients treated with trastuzumab before the diagnosis of BMs showed a lower number of intracranial metastases (p < 0.001. Patients with a HER2-positive tumor-subtype developed cerebellar metastases more often compared with HER2-negative patients (59.8% vs. 44.5%, p = 0.021, whereas patients with triple-negative primary tumors had leptomeningeal disease more often (31.4% vs. 18.3%, p = 0.038. The localization of Brain metastases (BMs was associated with prognosis: patients with leptomeningeal disease had shorter survival compared with patients without signs of leptomeningeal disease (median survival 3 vs. 5 months, p = 0.025. A shorter survival could also be observed in the patients with metastases in the occipital lobe (median survival 3 vs. 5 months, p = 0.012. Our findings suggest a different tumor cell homing to different brain regions depending on subtype and treatment.

  11. 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.

  12. Rationale for the Use of Upfront Whole Brain Irradiation in Patients with Brain Metastases from Breast Cancer

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    Agnes V. Tallet

    2014-05-01

    Full Text Available Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

  13. Brain metastases in lung cancer. Impact of prognostic factors on patient survival

    International Nuclear Information System (INIS)

    Smrdel, U.; Zwitter, M.; Kovac, V.

    2003-01-01

    Background. Brain metastases are common patterns of dissemination in lung cancer patients. In this paper we would like to assess the pattern of brain metastases in lung cancer patients and the impact of prognostic factors on the survival of lung cancer patients with brain metastases. Patients and methods. In the year 1998 there were 974 registered patients with lung cancer in Slovenia, six hundred and fifteen of them were treated at the Institute of Oncology Ljubljana and we analyzed them. Among 615 patients 137 (22.3 %) of them have had brain metastases during a natural course of disease. Results. For 12 patients presenting with solitary brain metastases (most of them were undertaken metastasectomy) median survival was 7.6 months, while in patients with multiple brain metastases the median survival was 2.8 months (p 0.0018). Of the 137 patients 45 (32.8 %) were small cell lung cancer patients, 43 (31.4 %) were adenocarcinoma patients and 19 (13.9 %) were squamous cell carcinoma patients. Patients with performance status (WHO scale) less than 2 had the median survival time 3.7 months while patients with performance status 2 or more had median survival time 2.7 moths (p=0.0448). Conclusions. Patients with solitary brain metastases had better survival comparing with those who had multiple metastases. It is surprisingly that the portion of brain metastases patients with adenocarcinoma is almost equal to those with small-call lung cancer therefore, the prophylactic cranial radiation becomes actual for both groups of patients. The performance status of patients with brain metastases remains very important prognostic factor. (author)

  14. Advances in Diagnosis and Treatment of Brain Metastases from the Primary Lung Cancer

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    Yi LIU

    2013-07-01

    Full Text Available Lung cancer with brain metastasis was 23% to 65%, and is the most common type in brain metastasis tumors with the poor prognosis. At present, diagnosis and treatment of brain metastases from lung carcinoma and its molecular mechanism have become one hot spot of amount researches. Here, we made a systematic review of the progress of the clinical features, diagnosis and treatment of brain metastases from lung and its molecular mechanism.

  15. Management of Brain Metastases.

    Science.gov (United States)

    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.

  16. Do patients with very few brain metastases from breast cancer benefit from whole-brain radiotherapy in addition to radiosurgery?

    International Nuclear Information System (INIS)

    Rades, Dirk; Huttenlocher, Stefan; Hornung, Dagmar; Blanck, Oliver; Schild, Steven E; Fischer, Dorothea

    2014-01-01

    An important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients. Fifty-eight patients with 1–3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy. The treatment regimen had no significant impact on local control in the univariate analysis (p = 0.59). Age ≤59 years showed a trend towards improved local control on univariate (p = 0.066) and multivariate analysis (p = 0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p = 0.040) and ECOG 0–1 (p = 0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p = 0.039) and performance status (p = 0.028) maintained significance on multivariate analysis. ECOG 0–1 was positively correlated with survival on univariate analysis (p < 0.001); age ≤59 years showed a strong trend (p = 0.054). On multivariate analysis, performance status (p < 0.001) and age (p = 0.041) were significant. In breast cancer patients with few brain metastases, radiosurgery plus whole-brain

  17. 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.

  18. Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography

    DEFF Research Database (Denmark)

    Lassen, U; Andersen, P; Daugaard, G

    1998-01-01

    for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor r......Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors...

  19. Late brain metastases from breast cancer: clinical remarks on 11 patients and review of the literature.

    Science.gov (United States)

    Piccirilli, Manolo; Sassun, Tanya Enny; Brogna, Christian; Giangaspero, Felice; Salvati, Maurizio

    2007-01-01

    Late brain metastases from breast cancer are a rare event. Only a few cases have been reported in the English literature. The authors describe the clinical and pathological remarks, together with treatment modalities, removal extent and overall survival, of 11 patients in whom brain metastases were detected more than 10 years from the primary tumor. Between January 1997 and April 2001, we hospitalized 11 patients, all females, with a histologically proven diagnosis of brain metastasis from breast invasive ductal carcinoma. We defined 'late metastasis' as those metastases that appeared at least 10 years after the breast cancer diagnosis. The median age at the moment of brain metastasis diagnosis was 59 years (range, 47-70), with a median latency time from breast cancer diagnosis of 16 years (range, 11-30). Ten patients underwent surgery followed by adjuvant radiotherapy (whole brain radiotherapy). Two of them received, after whole brain radiotherapy, stereotaxic radio surgery treatment. One patient had stereotaxic brain biopsy, performed by neuronavigator, followed by palliative corticosteroid therapy. Median survival after brain metastasis diagnosis was 28 months (range, 3 months-4 years). Although late brain metastases are a rare event, specific neurologic symptoms and neuroradiological evidence of a cerebral neoplasm should be correlated to the presence of a cerebral metastasis, in a patient with a previous history of breast cancer. The longer latency time from breast cancer to brain metastasis could be explained by the "clonal dominance" theory and by different genetic alterations of the metastatic cell, which could influence the clinical history of the disease.

  20. SPECIFIC CHARACTERISTICS OF BRAIN METASTASIZING IN PATIENTS WITH LUMINAL SUBTYPE OF BREAST CANCER

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    A. S. Balkanov

    2016-01-01

    Full Text Available Background: More than half of female patients with breast cancer are diagnosed with a  luminal subtype of the disease; however, specific characteristics of its metastases to the brain have been not well studied, unlike those of HER2 positive and triple negative subtypes. Aim: A  comparative analysis of characteristics of metastatic brain lesions in patients with luminal breast cancer. Materials and methods: The time from surgery for breast cancer to the first recurrence and to metastatic brain lesions (assessed by contrast-enhanced MRI imaging was measured in 41 patients with luminal subtype of breast cancer (median age, 49.5±9.6  years, depending on a  diameter of the primary tumor and numbers of involved axillary lymph nodes. Results: The time interval to occurrence of brain metastases in luminal subtype of breast cancer is not associated with the size of the tumor. If≥4  axillary lymph nodes are involved (N2–3, brain metastases are identified much earlier (p<0.05 than in patients with N0–1 (34.5±23.9 months and 62.7±50 months, respectively. Neither the size nor the involvement of axillary lymph nodes has any impact on the rates of metastatic lesion to the brain during the first recurrence. Conclusion: Brain metastases occur at a much shorter time in those patients of luminal subtype of breast cancer who have metastases in≥4  axillary lymph nodes. Brain metastases develop in 50% of patients with the first recurrence of the luminal subtype of breast cancer.

  1. 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

  2. Hemorrhagic brain metastases

    International Nuclear Information System (INIS)

    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)

  3. Brain metastases in patients who receive trastuzumab-containing chemotherapy for HER2-overexpressing metastatic breast cancer

    International Nuclear Information System (INIS)

    Ono, Makiko; Ando, Masashi; Yunokawa, Mayu

    2009-01-01

    Recently, a high rate of brain metastases has been reported among patients with human epidermal growth factor receptor (HER2)-overexpressing metastatic breast cancer who were treated with trastuzumab. The present study examined risk factors for the development of brain metastasis in patients with HER2-overexpressing breast cancer who were treated with trastuzumab. We retrospectively reviewed 204 patients with HER-2-overexpressing breast cancer who were treated with a trastuzumab-containing regimen between 1999 and 2006. Patients with clinical symptoms were diagnosed as having brain metastases when brain magnetic resonance imaging (MRI) or a computed tomography (CT) scan revealed positive findings for brain metastases. The median follow-up time of this cohort was 53.6 months. Among the patients who received a trastuzumab-containing regimen, 74 patients (36.3%) developed brain metastases. The median survival from the diagnosis of brain metastases was 13.5 months (95% confidence interval [CI], 12.2-14.7 months). The median time interval between the beginning of trastuzumab treatment and the diagnosis of brain metastases was 13.6 months (range, 0.0-45.8 months). Among patients with brain metastases, the median overall survival period was 39 months. A multivariate logistic regression analysis showed that age (≤50 years), recurrent breast cancer, and liver metastases were significant risk factors for the development of brain metastases. Patients with HER2-overexpressing breast cancer treated with trastuzumab had a high incidence of brain metastases (36.3%). Routine screening for brain metastases 1 year after the start of trastuzumab treatment, may be warranted in younger patients (≤50 years) who had recurrent breast cancer with liver metastases. (author)

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

    International Nuclear Information System (INIS)

    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

  5. 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

  6. NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer

    International Nuclear Information System (INIS)

    Adkins, Chris E.; Nounou, Mohamed I.; Hye, Tanvirul; Mohammad, Afroz S.; Terrell-Hall, Tori; Mohan, Neel K.; Eldon, Michael A.; Hoch, Ute; Lockman, Paul R.

    2015-01-01

    Brain metastases are an increasing problem in women with invasive breast cancer. Strategies designed to treat brain metastases of breast cancer, particularly chemotherapeutics such as irinotecan, demonstrate limited efficacy. Conventional irinotecan distributes poorly to brain metastases; therefore, NKTR-102, a PEGylated irinotecan conjugate should enhance irinotecan and its active metabolite SN38 exposure in brain metastases leading to brain tumor cytotoxicity. Female nude mice were intracranially or intracardially implanted with human brain seeking breast cancer cells (MDA-MB-231Br) and dosed with irinotecan or NKTR-102 to determine plasma and tumor pharmacokinetics of irinotecan and SN38. Tumor burden and survival were evaluated in mice treated with vehicle, irinotecan (50 mg/kg), or NKTR-102 low and high doses (10 mg/kg, 50 mg/kg respectively). NKTR-102 penetrates the blood-tumor barrier and distributes to brain metastases. NKTR-102 increased and prolonged SN38 exposure (>20 ng/g for 168 h) versus conventional irinotecan (>1 ng/g for 4 h). Treatment with NKTR-102 extended survival time (from 35 days to 74 days) and increased overall survival for NKTR-102 low dose (30 % mice) and NKTR-102 high dose (50 % mice). Tumor burden decreased (37 % with 10 mg/kg NKTR-102 and 96 % with 50 mg/kg) and lesion sizes decreased (33 % with 10 mg/kg NKTR-102 and 83 % with 50 mg/kg NKTR-102) compared to conventional irinotecan treated animals. Elevated and prolonged tumor SN38 exposure after NKTR-102 administration appears responsible for increased survival in this model of breast cancer brain metastasis. Further, SN38 concentrations observed in this study are clinically achieved with 145 mg/m 2 NKTR-102, such as those used in the BEACON trial, underlining translational relevance of these results. The online version of this article (doi:10.1186/s12885-015-1672-4) contains supplementary material, which is available to authorized users

  7. Radiotherapy of brain metastases of a breast cancer: present strategies, technological innovations and biological perspectives

    International Nuclear Information System (INIS)

    Chargari, C.; Vedrine, L.; Bauduceau, O.; Jacob, J.; Fayolle, M.; Chargari, C.; Campana, F.; Pierga, J.Y.; Idrissi, H.R.; Fourquet, A.; Kirova, Y.

    2010-01-01

    The authors propose an overview of strategies which are presently used for the treatment of brain metastases related to a breast cancer. They outline the perspectives and recent developments of encephalic irradiation with new technologies allowing an increased conformation to be obtained, and also in terms of radiosensitization and radioprotection experiences. Short communication

  8. Metabolic Profiles of Brain Metastases

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    Tone F. Bathen

    2013-01-01

    Full Text Available Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49 were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01, irrespective of their primary origin. The principal component analysis (PCA showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01, indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.

  9. The role of chemotherapy in brain metastases

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    Ohori, Hisatsugu; Takahashi, Shin; Ishioka, Chikashi

    2007-01-01

    Brain metastases are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases have a very poor prognosis with a median survival of 1-2 months. Despite the use of surgery and radiotherapy including whole-brain radiation and stereotactic radiosurgery to locally control brain metastases, survival times for those patients has not improved. Although chemotherapy plays a limited role in the treatment of brain metastases, metastases from lung or breast cancer are often well-controlled by chemotherapy. Accumulating evidence suggest that brain metastases are equally sensitive to chemotherapy as are metastases elsewhere in the body in particular chemotherapy-naive cases. Finally, since nearly a half of patients with brain metastases die from progression of systemic disease, control of systemic disease as well as intracranial disease are both important. (author)

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

    Science.gov (United States)

    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.

  11. Bevacizumab in the treatment of five patients with breast cancer and brain metastases: Japan Breast Cancer Research Network-07 trial

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    Yamamoto D

    2012-09-01

    Full Text Available Daigo Yamamoto,1,3 Satoru Iwase,2 Yu Tsubota,1 Noriko Sueoka,1 Chizuko Yamamoto,3 Kaoru Kitamura,4 Hiroki Odagiri,5 Yoshinori Nagumo61Department of Surgery, Kansai Medical University, Hirakata, Osaka, 2Department of Palliative Medicine, University of Tokyo Hospital, Tokyo, 3Department of Internal Medicine, Seiko Hospital, Neyagawa, Osaka, 4Breast Unit, Nagumo Clinic, Fukuoka, 5Department of Surgery, Hirosaki National Hospital, Hirosaki, 6Breast Unit, Nagumo Clinic, Tokyo, JapanBackground: Brain metastases from breast cancer occur in 20%–40% of patients, and the frequency has increased over time. New radiosensitizers and cytotoxic or cytostatic agents, and innovative techniques of drug delivery are still under investigation.Methods: Five patients with brain metastases who did not respond to whole-brain radiotherapy and then received bevacizumab combined with paclitaxel were identified using our database of records between 2011 and 2012. The clinicopathological data and outcomes for these patients were then reviewed.Results: The median time to disease progression was 86 days. Of five patients, two (40% achieved a partial response, two had stable disease, and one had progressive disease. In addition, one patient with brain metastases had ptosis and diplopia due to metastases of the right extraocular muscles. However, not only the brain metastases, but also the ptosis and diplopia began to disappear after 1 month of treatment. The most common treatment-related adverse events (all grades were hypertension (60%, neuropathy (40%, and proteinuria (20%. No grade 3 toxicity was seen. No intracranial hemorrhage was observed.Conclusion: We present five patients with breast cancer and brain metastases, with benefits from systemic chemotherapy when combined with bevacizumab.Keywords: brain, bevacizumab, metastatic breast cancer

  12. Emerging role of brain metastases in the prognosis of breast cancer patients

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    Hambrecht A

    2011-08-01

    Full Text Available Amanda Hambrecht1,2, Rahul Jandial2, Josh Neman21Department of Biology, University of Southern California; 2Department of Neurosurgery, Beckman Research Institute, City of Hope National Cancer Center, CA, USAAbstract: Cancer starts with one rogue cell. Through mutations and genomic alterations, the cell acquires specific and stem cell-like characteristics necessary for invasion of a distant organ and ultimately metastasis. Metastatic brain cancer is a particularly formidable disease because of its poor prognosis and the highly resistant nature of the tumor to chemotherapy. Although several types of primary tumors have a tendency to metastasize to the brain, the incidence of brain metastases has increased dramatically in some subsets of breast cancer patients. Several conventional treatments are available, but success is limited and often short-lived. Given that no standard treatment options exist, there is a significant need to investigate the biology of these clinically recalcitrant tumors. Keywords: metastasis, breast cancer, blood-brain barrier, epithelial-mesenchymal transition, mesenchymal-epithelial transition

  13. 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

  14. 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.

  15. Selection of optimal treatment scheme for brain metastases of non-small cell lung cancer

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    Dong Mingxin; Zhao Tong; Huang Jingzi; Yu Shukun; Ma Yan; Tian Zhongcheng; Jin Xiangshun; Quan Jizhong; Liu Jin; Wang Dongxu

    2006-01-01

    Objective: To select the optimal treatment scheme for brain metastases of non-small cell lung cancers (NSCLCs). Methods: Seventy-two NSCLC cases diagnosesd by pathology with brain metastases were randomly classified into three groups, Group I, 24 cases with whole brain conventional external fractioned irradiation of D T 36-41 Gy/4-5 w, Group II, 22 eases with y-knife treatment plus whole brain conventional external fractioned irradiation, and Group III, 26 cases with γ-knife plus whole brain conventional external fractioned irradiation in combination with chemotherapy of Vm-26. The surrounding area of tumor was strictly covered with 50% para-central-dosal curve in γ-knife treatment (D T 16-25 Gy with a mean of 16 Gy). The muirleaf collimator was selected according to the volume of tumors. Chemotherapy of Vm-26 (60 mg/m 2 d1-3) was applied during the treatment with whole brain conventional external fractioned irradiation (D T 19-29 Gy/2-3 w), 21 days in a period, 2 periods in total. Results: The median survival time was estimated to be 6.0 months (ranged from 1.2 to 19.0 months) in the Group I, 9.2 months (4.4-30 months) in the Group II, and 10.8 months (5.2-42.2 months) in the Group III. The 1-year and 2-year survival rates were 34.6% and 12.6% , 62.2% and 30.2%, and 70.8% and 35.6% respectively in Group I, Group II, and Group III, respectively. Conclusion: For brain metastases of NSCLC, γ-knife plus whole brain conventional external fractioned irradiation combined with treatment of Vm-26 had a significantly beneficial influence on improvement of the local control and 1-year and 2-year survival. There was no complaint about the side-effects of the treatment. (authors)

  16. 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.

  17. 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

  18. Longitudinal MRI evaluation of intracranial development and vascular characteristics of breast cancer brain metastases in a mouse model.

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    Heling Zhou

    Full Text Available Longitudinal MRI was applied to monitor intracranial initiation and development of brain metastases and assess tumor vascular volume and permeability in a mouse model of breast cancer brain metastases. Using a 9.4T system, high resolution anatomic MRI and dynamic susceptibility contrast (DSC perfusion MRI were acquired at different time points after an intracardiac injection of brain-tropic breast cancer MDA-MB231BR-EGFP cells. Three weeks post injection, multifocal brain metastases were first observed with hyperintensity on T2-weighted images, but isointensity on T1-weighted post contrast images, indicating that blood-tumor-barrier (BTB at early stage of brain metastases was impermeable. Follow-up MRI revealed intracranial tumor growth and increased number of metastases that distributed throughout the whole brain. At the last scan on week 5, T1-weighted post contrast images detected BTB disruption in 160 (34% of a total of 464 brain metastases. Enhancement in some of the metastases was only seen in partial regions of the tumor, suggesting intratumoral heterogeneity of BTB disruption. DSC MRI measurements of relative cerebral blood volume (rCBV showed that rCBV of brain metastases was significantly lower (mean= 0.89±0.03 than that of contralateral normal brain (mean= 1.00±0.03; p<0.005. Intriguingly, longitudinal measurements revealed that rCBV of individual metastases at early stage was similar to, but became significantly lower than that of contralateral normal brain with tumor growth (p<0.05. The rCBV data were concordant with histological analysis of microvascular density (MVD. Moreover, comprehensive analysis suggested no significant correlation among tumor size, rCBV and BTB permeability. In conclusion, longitudinal MRI provides non-invasive in vivo assessments of spatial and temporal development of brain metastases and their vascular volume and permeability. The characteristic rCBV of brain metastases may have a diagnostic value.

  19. 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

  20. Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

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    Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

    2015-10-01

    The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. 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.

  2. BRAIN METASTASES OF GERM CELL TUMORS. THE RUSSIAN CANCER RESEARCH CENTER'S EXPERIENCE

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    A. A. Tryakin

    2014-07-01

    Full Text Available This paper analyzes the experience in treating 20 patients with nonseminomatous germ cell tumors metastasizing to the brain. It presents brain metastasis-associated factors: multiple lung metastases; IGCCCG poor prognosis; and a baseline human chorionic gonadotropin level of > 50000 mIU/ml. The authors have identified a group to be screened for brain metastasis, which includes patients with intermediate/poor prognosis and multiple lung metastases. Long-term survival was achieved in 45 % of patients with baseline brain damage and in 22 % of those with metastases revealed after first-line chemotherapy. The positive prognostic factors associated with long-term survival were a single brain lesion, no neurological symptoms, and achievement of clinical complete personse in the brain.

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

    International Nuclear Information System (INIS)

    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

  4. 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.

  5. Relative significance of surgery and radiotherapy in treatment of brain metastases of lung cancer

    International Nuclear Information System (INIS)

    Yamashita, Junkoh; Ohtsuka, Sinichi; Yamasaki, Toshiki; Gi, Hidefuku; Ha, Young-Soo; Handa, Hajime

    1983-01-01

    One hundred and sixteen cases of brain metastases of lung cancer were retrospectively analysed with special reference to the relative significance of surgery and radiotherapy. The median survival time from diagnosis of brain metastases was 1.2 months in 27 cases without treatment, 2.5 months in 51 cases treated by surgery alone, 4.2 months in 31 cases treated by radiotherapy alone and 6.5 months in 7 cases treated by surgery and radiotherapy. The survival rate in patients treated by radiotherapy was significantly better than in those not treated by radiotherapy. However, the effect of surgery was not significant in prolongation of survival time. On the other hand, the rate of improvement in neurological symptoms assessed at one month after the initiation of treatment was 80.9% in 47 cases treated by surgery and 19.4 % in 31 cases treated by radiotherapy. The result suggested that surgery is superior to radiotherapy in alleviating neurological symptoms. It is important to understand the nature of effect of each treatment. A better result will be anticipated by proper selection or combination of these treatments. (author)

  6. Concurrent radiotherapy and fotemustine for brain metastases of non small cell cancer of the lung

    International Nuclear Information System (INIS)

    Pignon, T.; Ruggieri, S.; Orabona, P.; Muracciole, X.; Juin, P.; Astoul, P.; Vialette, J.P.; Boutin, C.

    1994-01-01

    The radiotherapy is the most employed in the treatment of cerebral metastases, even if results are deceptive. The tests with chemotherapy are not better and the nitrosoureas remain the most employed drugs. The fotemustin is a new one which can give good results for bearing cerebral metastases patients's response. The associations radiotherapy and chemotherapy are developing to potentiate radiotherapy action but are still a little studied in the cases of cerebral metastases; that is why we choose to treat in an open study the patients bearers of cerebral metastases in lungs cancers with no little cells. 18 refs

  7. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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

  10. Prognostic indices in stereotactic radiotherapy of brain metastases of non-small cell lung cancer.

    Science.gov (United States)

    Kaul, David; Angelidis, Alexander; Budach, Volker; Ghadjar, Pirus; Kufeld, Markus; Badakhshi, Harun

    2015-11-26

    Our purpose was to analyze the long-term clinical outcome and to identify prognostic factors after Linac-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) on patients with brain metastases (BM) from non-small cell lung cancer (NSCLC). We performed a retrospective analysis of survival on 90 patients who underwent SRS or FSRT of intracranial NSCLC metastases between 04/2004 and 05/2014 that had not undergone prior surgery or whole brain radiotherapy (WBRT) for BM. Follow-up data was analyzed until May 2015. Potential prognostic factors were examined in univariable and multivariable analyses. The Golden Grading System (GGS), the disease-specific graded prognostic assessment (DS-GPA), the RADES II prognostic index as well as the NSCLC-specific index proposed by Rades et al. in 2013 (NSCLC-RADES) were calculated and their predictive values were tested in univariable analysis. The median follow-up time of the surviving patients was 14 months. The overall survival (OS) rate was 51 % after 6 months and 29.9 % after 12 months. Statistically significant factors of better OS after univariable analysis were lower International Union Against Cancer (UICC) stage at first diagnosis, histology of adenocarcinoma, prior surgery of the primary tumor and lower total BM volume. After multivariable analysis adenocarcinoma histology remained a significant factor; higher Karnofsky Performance Score (KPS) and the presence of extracranial metastases (ECM) were also significant. The RADES II and the NSCLC-RADES indices were significant predictors of OS. However, the NSCLC-RADES failed to differentiate between intermediate- and low-risk patients. The DS-GPA and GGS were not statistically significant predictors of survival in univariable analysis. The ideal prognostic index has not been defined yet. We believe that more specific indices will be developed in the future. Our results indicate that the histologic subtype of NSCLC could add to the prognostic

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. 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.

  15. 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.

  16. Radiation therapy of brain metastases

    International Nuclear Information System (INIS)

    Obata, Yasunori; Morita, Kozo; Watanabe, Michiko; Niwa, Kokichi

    1982-01-01

    From January 1974 to December 1980, 104 patients with brain metastases were treated by irradiation to the whole brain. The results of treatment and the relation between CT images and effectiveness of irradiation were analized. The lung was the most common site of the primary tumor (67/104, 64.4%). The breast was a distant second in frequency (13/104, 12.5%) and fewer cases had other primary tumors (24/104, 23.1%). There were 63 males and 41 females. Their mean age was 56.0 years old. The interval between onset of symptoms from primary disease and of those from the brain metastases were 26.5 months for the breast cancer, 7.6 months for undifferentiated carcinoma of the lung and 13.2 months for all patients. Significant neurologic improvement was obtained in 85.7% of the patients (86 cases) irradiated as previous plans. The survival for the entire group of patients (86 cases) was 60.5% at 3 months, 31.4% at 6 months, 11.6% at 12 months an 3.5% at 18 months. Multiplicity of the metastatic brain tumror did not affect the prognosis but the control of the primary lesion affected the prognosis. The CT images of 41 cases before treatment revealed the enhanced mass was mainly homogeneous for the case with the breast cancer and mainly ring like for the case with squamous cell carcinoma of the lung. But the characters of the enhanced mass did not affect the prognosis. On the other hand, the analysis of the CT images of 37 cases before and after the treatment revealed the relation between the tumor regression and the improvement in neurologic symptoms. (J.P.N.)

  17. 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

  18. 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

    Science.gov (United States)

    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

  19. 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.

  20. [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.

  1. Inguinal metastases from testicular cancer

    DEFF Research Database (Denmark)

    Daugaard, Gedske; Karas, Vladimir; Sommer, Peter

    2006-01-01

    To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease.......To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease....

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

    Science.gov (United States)

    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.

  3. Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Halasz, Lia M., E-mail: lhalasz@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Weeks, Jane C.; Neville, Bridget A.; Taback, Nathan [Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Punglia, Rinaa S. [Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2013-02-01

    Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.

  4. Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United States

    International Nuclear Information System (INIS)

    Halasz, Lia M.; Weeks, Jane C.; Neville, Bridget A.; Taback, Nathan; Punglia, Rinaa S.

    2013-01-01

    Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.

  5. 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,

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

    Science.gov (United States)

    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.

  7. Neurosurgical Treatment of Breast Cancer Metastases to the Neurocranium

    OpenAIRE

    Stark, Andreas M.

    2010-01-01

    Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4–11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present...

  8. Bone metastases from gastric cancer

    International Nuclear Information System (INIS)

    Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi

    1983-01-01

    We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N 0 or N 1 regional lymph node metastases, highly deferenciated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone stastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer. (author)

  9. Analysis of outcome in patients irradiated for brain metastases of lung (no oatcell) cancer

    International Nuclear Information System (INIS)

    Lione, Marcelo; Tissera, Norberto

    2004-01-01

    Purpose: To correlate our findings with those of the international literature and identify the factors related to survival. Material and methods: Fifty patients with central nervous system metastases of non-small cell lung cancer were evaluated. Holocranial radiotherapy was performed with a daily dose of 1.8 Gy and a total dose of 50.4 Gy. Results: Overall survival of all patients at 6 months, 1 year and 2 years was 37%, 27% and 5% respectively. Mean survival was 5 months; 9 months for the group with a favorable outcome and 4 months for the group with an unfavorable outcome. Conclusion: The results are similar to those published in the international literature. Factors that relate to survival are: age, performance status, and the presence or absence of metastases in other sites. (author)

  10. Role of palliative radiotherapy in brain metastases

    Directory of Open Access Journals (Sweden)

    Ramesh S Bilimagga

    2009-01-01

    Full Text Available Background: Brain metastases are a common manifestation of systemic cancer and exceed primary brain tumors in number and are a significant cause of neurologic problems. They affect 20-40% of all cancer patients. Aggressive management of brain metastases is effective in both symptom palliation and prolonging the life. Radiotherapy has a major role to play in the management of brain metastases. AIM: The aim of the study was to know the outcome of palliative radiotherapy in symptomatic brain metastases in terms of improvement in their performance status. Materials and Methods: This is a retrospective study of 63 patients diagnosed to have brain metastases and treated with palliative whole brain radiotherapy to a dose of 30 Gy in 10 fractions over two weeks between June 1998 and June 2007. Diagnosis was done in most of the cases with computed tomography scan and in a few with magnetic resonance imaging. Improvement in presenting symptoms has been assessed in terms of improvement in their performance status by using the ECOG scale. Results: Fifty-four patients completed the planned treatment. Eight patients received concurrent Temozolamide; 88% of patients had symptom relief at one month follow-up; 39/54 patients had a follow-up of just one to three months. Hence survival could not be assessed in this study. Conclusion: External beam radiotherapy in the dose of 30 Gy over two weeks achieved good palliation in terms improvement in their performance status in 88% of patients. Addition of concurrent and adjuvant Timozolamide may improve the results.

  11. 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.

    Science.gov (United States)

    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.

  12. 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.)

  13. Stereotactic radiosurgery for brain metastases

    International Nuclear Information System (INIS)

    Obedian, E.; Lotbiniere, A.C.J. de; Haffty, B.G.; Piepmeier, J.M.; Fischer, D.B.; Knisely, J.P.S.

    1997-01-01

    Purpose: This study evaluates the influence of several prognostic factors on overall survival and progression free survival in patients undergoing stereotactic radiosurgery (SRS) for brain metastases. Materials and Methods: Records of 61 coecutive patients with pathologically confirmed extra-cranial malignancies undergoing SRS at Yale University School of Medicine between 12/18/91 and 7/2/96 were reviewed. All patients underwent head frame localization and CT and/or MRI based treatment planning. Outcome was analyzed with respect to age, number of lesions, size of lesions, location of lesions, site and stage of primary tumor, status of primary tumor at time of SRS, history of whole brain radiation therapy (WBRT), surgery, and/or chemotherapy prior to or after SRS, delay in SRS from diagnosis of brain metastases, dose of radiation delivered, and brain metastasis free interval. Both overall survival and progression free survival were analyzed by the Kaplan-Meier method. Tests for statistical significance were performed using the Cox proportional hazards model. Results: Median follow-up was 29 months. 3% ((8(61))) of patients displayed evidence of progressive disease at the site of SRS, and 87% ((53(61))) of patients have died. Overall and progression free survival rates for the entire cohort of patients were 43.8% and 89.5% at 1 year and 11.1% and 71.4% at 2 years, respectively. Patients undergoing SRS for a solitary brain metastasis had a significant improvement in overall survival with 1 year survival rates of 52.6% vs. 32.7% for patients undergoing SRS for more than 1 brain metastasis (p=0.002). Patients who presented with progressive systemic disease at the time of SRS had an inferior overall survival with a 1 year survival rate of 15.4% compared to patients with presumed/known stable disease who had a 1 year survival rate of 51.5%/54.2% (p<0.001). Patients treated for cerebral metastases had a higher progression free survival compared to patients undergoing SRS

  14. Radiation therapy of brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Sauer, R; Huenig, R [Kantonsspital Basel (Switzerland). Universitaetsinstitut fuer Medizinische Radiologie

    1975-08-01

    Experiences are reported obtained with radiation therapy of brain metastases in 121 patients during the last 15 years. The treatment to a lesser extent aimed at prolongation of survival but much more at the attempt to alleviate troubles and to spare pain. The indication thus involved medical points of view as well as ethical ones. The radiotherapy of cerebral metastases comprises the whole cranial volume and requires a focal dose of minimally 4,000 R within four weeks. In 53% of the patients, the regression of neurological symptoms was considerable, in 18% even complete, partly beginning already after a few days of treatment. The number of recurrences was small. Under conditions of rigorous indication, the radiation therapy of brain metastases offers a rewarding palliative measure.

  15. 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.

  16. Consensus for the brain metastases treatment

    International Nuclear Information System (INIS)

    Rabadan, Alejandra; Diez, Blanca; Martinez, Ana M.; Antico, Julio; Saidon, Patricia; Christiansen, Silvia; Rojas, Galeno

    2006-01-01

    The advancement in oncology therapies has made brain metastases treatment a major factor influencing the survival time and quality of life of patients with cancer. Although there are numerous publications on the issue, there is not yet to be consensus regarding the best strategy for treatment, which is probably due to population heterogeneity in terms of functional status, type of neoplasia, control of the systemic disease, and the number and localization of the lesions in the central nervous system. Our objective is to present general recommendations based on rational analysis in order to guide the practical management of brain metastases. With this purpose, a multidisciplinary team composed by neurosurgeons, neuro-oncologists, neuro-pathologist, radio therapist and neurologists was brought together, conducting a thorough search, in english and spanish, for publications in Pub- Med from 1980 to July 2006 (the starting period was set at the beginning of use of RM in medical practice). Review and original articles with n= or >20 were selected. Also, book chapters of renowned authors in the different consulted areas were included. The assessment of the literature, in addition to the experience of the authors allowed for the development of the 'Consensus for the brain metastases treatment'. Finally, the authors expect the present work will contribute to the multidisciplinary approach for the management of brain metastases with simple and practical recommendations, and probably stimulating future developments in this field. (author)

  17. 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....

  18. Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

    International Nuclear Information System (INIS)

    Garsa, Adam A.; Badiyan, Shahed N.; DeWees, Todd; Simpson, Joseph R.; Huang, Jiayi; Drzymala, Robert E.; Barani, Igor J.; Dowling, Joshua L.; Rich, Keith M.; Chicoine, Michael R.; Kim, Albert H.; Leuthardt, Eric C.; Robinson, Clifford G.

    2014-01-01

    Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective

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

    International Nuclear Information System (INIS)

    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.

  20. 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

  1. Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2009-01-01

    Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

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

    Science.gov (United States)

    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.

  3. 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

  4. An Institutional Retrospective Analysis of 93 Patients with Brain Metastases from Breast Cancer: Treatment Outcomes, Diagnosis-Specific Prognostic Factors

    Directory of Open Access Journals (Sweden)

    Delphine Antoni

    2012-12-01

    Full Text Available To evaluate the prognostic factors and indexes of a series of 93 patients with breast cancer and brain metastases (BM in a single institution. Treatment outcomes were evaluated according to the major prognostic indexes (RPA, BSBM, GPA scores and breast cancer subtypes. Independent prognostic factors for overall survival (OS were identified. The median OS values according to GPA 0–1, 1.5–2, 2.5–3 and 3.5–4, were 4.5, 9.5, 14.2 and 19.1 months, respectively (p < 0.0001 and according to genetic subtypes, they were 5, 14.2, 16.5 and 17.1 months for basal-like, luminal A and B and HER, respectively (p = 0.04. Using multivariate analysis, we established a new grading system using the six factors that were identified as indicators of longer survival: age under 60 (p = 0.001, high KPS (p = 0.007, primary tumor control (p = 0.05, low number of extracranial metastases and BM (p = 0.01 and 0.0002, respectively and triple negative subtype (p = 0.002. Three groups with significantly different median survival times were identified: 4.1, 9.5 and 26.3 months, respectively (p < 0.0001. Our new grading system shows that prognostic indexes could be improved by using more levels of classification and confirms the strength of biological prognostic factors.

  5. Multiple metastases from ovarian cancer

    African Journals Online (AJOL)

    Ovarian cancer affects women in the age group >60 years much ... ovarian cancer presenting with liver and thoracic vertebral metastases 4 months after ... manifested by parenchymal liver or lung ... categorised as stage Ic as per International.

  6. Outcome and prognostic factors in single brain metastases from small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bernhardt, Denise; Koenig, Laila [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Adeberg, Sebastian; Debus, Juergen [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Bozorgmehr, Farastuk; Thomas, Michael; Steins, Martin [Heidelberg University, Department of Thoracic Oncology, Thoraxklinik, Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); Opfermann, Nils; Hoerner-Rieber, Juliane; Rieken, Stefan [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Kappes, Jutta [Heidelberg University, Department of Pneumology, Thoraxklinik, Heidelberg (Germany); Unterberg, Andreas [University Hospital Heidelberg, Department of Neurosurgery, INF 400, Heidelberg (Germany); Herth, Felix [Heidelberg University, Department of Pneumology, Thoraxklinik, Heidelberg (Germany); German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); Heussel, Claus Peter [German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); University of Heidelberg, Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik, Heidelberg (Germany); University of Heidelberg, Diagnostic and Interventional Radiology, Heidelberg (Germany); Warth, Arne [German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (DE); Heidelberg University, Institute of Pathology, Heidelberg (DE)

    2018-02-15

    Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1-4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT. A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS. The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06-4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11-0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14-4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35-0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15-0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09-4.45; p = 0.028). Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response

  7. 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

  8. Understanding Heterogeneity and Permeability of Brain Metastases in Murine Models of HER2-Positive Breast Cancer Through Magnetic Resonance Imaging: Implications for Detection and Therapy

    Directory of Open Access Journals (Sweden)

    Donna H. Murrell

    2015-06-01

    Full Text Available OBJECTIVES: Brain metastases due to breast cancer are increasing, and the prognosis is poor. Lack of effective therapy is attributed to heterogeneity of breast cancers and their resulting metastases, as well as impermeability of the blood–brain barrier (BBB, which hinders delivery of therapeutics to the brain. This work investigates three experimental models of HER2+ breast cancer brain metastasis to better understand the inherent heterogeneity of the disease. We use magnetic resonance imaging (MRI to quantify brain metastatic growth and explore its relationship with BBB permeability. DESIGN: Brain metastases due to breast cancer cells (SUM190-BR3, JIMT-1-BR3, or MDA-MB-231-BR-HER2 were imaged at 3 T using balanced steady-state free precession and contrast-enhanced T1-weighted spin echo sequences. The histology and immunohistochemistry corresponding to MRI were also analyzed. RESULTS: There were differences in metastatic tumor appearance by MRI, histology, and immunohistochemistry (Ki67, CD31, CD105 across the three models. The mean volume of an MDA-MB-231-BR-HER2 tumor was significantly larger compared to other models (F2,12 = 5.845, P < .05; interestingly, this model also had a significantly higher proportion of Gd-impermeable tumors (F2,12 = 22.18, P < .0001. Ki67 staining indicated that Gd-impermeable tumors had significantly more proliferative nuclei compared to Gd-permeable tumors (t[24] = 2.389, P < .05 in the MDA-MB-231-BR-HER2 model. CD31 and CD105 staining suggested no difference in new vasculature patterns between permeable and impermeable tumors in any model. CONCLUSION: Significant heterogeneity is present in these models of brain metastases from HER2+ breast cancer. Understanding this heterogeneity, especially as it relates to BBB permeability, is important for improvement in brain metastasis detection and treatment delivery.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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.

  11. Radiosurgery for Large Brain Metastases

    International Nuclear Information System (INIS)

    Han, Jung Ho; Kim, Dong Gyu; Chung, Hyun-Tai; Paek, Sun Ha; Park, Chul-Kee; Jung, Hee-Won

    2012-01-01

    Purpose: To determine the efficacy and safety of radiosurgery in patients with large brain metastases treated with radiosurgery. Patients and Methods: Eighty patients with large brain metastases (>14 cm 3 ) were treated with radiosurgery between 1998 and 2009. The mean age was 59 ± 11 years, and 49 (61.3%) were men. Neurologic symptoms were identified in 77 patients (96.3%), and 30 (37.5%) exhibited a dependent functional status. The primary disease was under control in 36 patients (45.0%), and 44 (55.0%) had a single lesion. The mean tumor volume was 22.4 ± 8.8 cm 3 , and the mean marginal dose prescribed was 13.8 ± 2.2 Gy. Results: The median survival time from radiosurgery was 7.9 months (95% confidence interval [CI], 5.343–10.46), and the 1-year survival rate was 39.2%. Functional improvement within 1–4 months or the maintenance of the initial independent status was observed in 48 (60.0%) and 20 (25.0%) patients after radiosurgery, respectively. Control of the primary disease, a marginal dose of ≥11 Gy, and a tumor volume ≥26 cm 3 were significantly associated with overall survival (hazard ratio, 0.479; p = .018; 95% CI, 0.261–0.880; hazard ratio, 0.350; p = .004; 95% CI, 0.171–0.718; hazard ratio, 2.307; p = .006; 95% CI, 1.274–4.180, respectively). Unacceptable radiation-related toxicities (Radiation Toxicity Oncology Group central nervous system toxicity Grade 3, 4, and 5 in 7, 6, and 2 patients, respectively) developed in 15 patients (18.8%). Conclusion: Radiosurgery seems to have a comparable efficacy with surgery for large brain metastases. However, the rate of radiation-related toxicities after radiosurgery should be considered when deciding on a treatment modality.

  12. Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose Escalation Trial.

    Science.gov (United States)

    Choi, Clara Y H; Wakelee, Heather A; Neal, Joel W; Pinder-Schenck, Mary C; Yu, Hsiang-Hsuan Michael; Chang, Steven D; Adler, John R; Modlin, Leslie A; Harsh, Griffith R; Soltys, Scott G

    2017-09-01

    To determine the maximum tolerated dose (MTD) of vorinostat, a histone deacetylase inhibitor, given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLC) brain metastases. Secondary objectives were to determine toxicity, local failure, distant intracranial failure, and overall survival rates. In this multicenter study, patients with 1 to 4 NSCLC brain metastases, each ≤2 cm, were enrolled in a phase 1, 3 + 3 dose escalation trial. Vorinostat dose levels were 200, 300, and 400 mg orally once daily for 14 days. Single-fraction SRS was delivered on day 3. A dose-limiting toxicity (DLT) was defined as any Common Terminology Criteria for Adverse Events version 3.0 grade 3 to 5 acute nonhematologic adverse event related to vorinostat or SRS occurring within 30 days. From 2009 to 2014, 17 patients were enrolled and 12 patients completed study treatment. Because no DLTs were observed, the MTD was established as 400 mg. Acute adverse events were reported by 10 patients (59%). Five patients discontinued vorinostat early and withdrew from the study. The most common reasons for withdrawal were dyspnea (n=2), nausea (n=1), and fatigue (n=2). With a median follow-up of 12 months (range, 1-64 months), Kaplan-Meier overall survival was 13 months. There were no local failures. One patient (8%) at the 400-mg dose level with a 2.0-cm metastasis developed histologically confirmed grade 4 radiation necrosis 2 months after SRS. The MTD of vorinostat with concurrent SRS was established as 400 mg. Although no DLTs were observed, 5 patients withdrew before completing the treatment course, a result that emphasizes the need for supportive care during vorinostat administration. There were no local failures. A larger, randomized trial may evaluate both the tolerability and potential local control benefit of vorinostat concurrent with SRS for brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Role of surgery in brain metastases.

    Science.gov (United States)

    Laghari, Altaf Ali; Ahmed, Syed Ijlal; Shamim, Muhammad Shahzad

    2017-08-01

    Brain metastases remain the commonest type of brain tumour, being four times more common than primary brain tumours. Although surgical intervention may be recommended for one of various reasons in the management of these tumours, including but not limited to conformation of diagnosis, relief of mass effect, improvement of neurological status and prolongation of survival, the guidelines for management of brain metastases remain largely subjective and therefore controversial. Herein the authors have attempted to review some of the existing evidence on role of surgery in the management of brain metastases and have presented their selected guidelines for the readers.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  15. 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

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

    International Nuclear Information System (INIS)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    International Nuclear Information System (INIS)

    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.)

  19. [Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands].

    Science.gov (United States)

    Schmid, K W

    2015-11-01

    The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).

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

    Science.gov (United States)

    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.

  1. Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

    Directory of Open Access Journals (Sweden)

    Anja Kafka

    2014-06-01

    Full Text Available The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1, Dishevelled-3 (DVL3, E-cadherin (CDH1 and beta-catenin (CTNNB1. Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR/loss of heterozygosity (LOH. Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001. Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC were significantly associated to CDH1 LOH (p = 0.001. Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

  2. 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....

  3. 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.

  4. Concurrent radiotherapy and fotemustine for brain metastases of non small cell cancer of the lung. Association concomitante de radiotherapie et de fotemustine dans le traitement des metastases cerebrales des cancers du poumon non a petites cellules

    Energy Technology Data Exchange (ETDEWEB)

    Pignon, T.; Ruggieri, S.; Orabona, P.; Muracciole, X.; Juin, P. (Hopital de la Timone, 13 - Marseille (France)); Astoul, P.; Vialette, J.P.; Boutin, C. (Hopital de la Conception, 13 - Marseille (France))

    1994-01-01

    The radiotherapy is the most employed in the treatment of cerebral metastases, even if results are deceptive. The tests with chemotherapy are not better and the nitrosoureas remain the most employed drugs. The fotemustin is a new one which can give good results for bearing cerebral metastases patients's response. The associations radiotherapy and chemotherapy are developing to potentiate radiotherapy action but are still a little studied in the cases of cerebral metastases; that is why we choose to treat in an open study the patients bearers of cerebral metastases in lungs cancers with no little cells. 18 refs.

  5. A comparison of radiotherapy with radiotherapy plus surgery for brain metastases from urinary bladder cancer. Analysis of 62 patients

    Energy Technology Data Exchange (ETDEWEB)

    Engenhart-Cabillic, Rita [Dept. of Radiotherapy and Radiation Oncology, Philipps Univ. Marburg (Germany); Fokas, Emmanouil; Henzel, Martin

    2010-10-15

    Purpose: To evaluate the role of radiotherapy (RT) and prognostic factors in 62 patients with brain metastases from transitional cell carcinoma (TCC) of the urinary bladder. Patients and Methods: 62 patients received either RT (n = 49), including whole-brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS), or surgery (OP) combined with WBRT (n = 13). Overall survival (OS), intracerebral control (ICC) and local control (LC) were retrospectively analyzed. Six potential prognostic factors were assessed: age, gender, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to RT. Results: Median OS and ICC for the entire cohort were 9 and 7 months. No significant difference between RT and OP + RT was found for OS (p = 0.696) and ICC (p = 0.996). On multivariate analysis, improved OS was associated with lack of extracerebral metastases (p < 0.001) and RPA class (p < 0.001), and ICC with the latter (p < 0.001). SRS-incorporating RT resulted in 1-, 2-, and 3-year LC probability of 78%, 66%, and 51%. No association between LC and any of the potential prognostic factors was observed. The results of the subgroup RPA class analyses were similar to the entire cohort. Conclusion: Patient outcome for the RT-alone arm was not significantly different from OP + RT. SRS-incorporating treatment offers excellent LC rates. RPA class and the presence of extracerebral metastases demonstrated a significant prognostic role for survival. The latter should be used as stratification factors in randomized trials and can help define the cohort of patients that may benefit from more aggressive therapies. (orig.)

  6. Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death

    International Nuclear Information System (INIS)

    Le Scodan, Romuald; Jouanneau, Ludivine; Massard, Christophe; Gutierrez, Maya; Kirova, Youlia; Cherel, Pascal; Gachet, Julie; Labib, Alain; Mouret-Fourme, Emmanuelle

    2011-01-01

    To access the prognostic significance of HER-2 overexpression, the effect of trastuzumab and the cause of death in patients with brain metastases (BM) from breast cancer (BC). We analyzed the outcome of 130 patients with BM from BC who received whole-brain radiotherapy (WBRT) (without surgery or radiosurgery) between January 1998 and April 2006. Demographic data, tumor characteristics, and treatments were prospectively recorded. The impact of HER-2 overexpression and trastuzumab-based therapy on overall survival (OS) and the cause of death were evaluated. The median follow-up for the whole population was 6.25 months (mean: 9.15; range: 0.23-53). The median survival time and 1-year survival rates after BM diagnosis were 7.43 months and 35.8% (95% CI: 28-45.7) respectively. The median survival time for HER-2 negative patients (n = 78), HER-2 positive patients not treated with trastuzumab (n = 20) and HER-2 positive patients treated with trastuzumab (n = 32) were 5.9 months, 5.6 months and 19.53 months, respectively. The 1-year survival rates were 26.1%, 29.2% and 62.6% respectively, (p < 0.004). Among the 18 HER-2 positive patients treated with trastuzumab who died, 11 (61%) apparently succumbed from CNS progression, in the face of stable or responsive non-CNS disease. Trastuzumab-based therapy was associated with a 51% reduction in the risk of death (multiadjusted hazard ratio: 0.49; 95% CI, 0.29-0.83). In our experience, trastuzumab-based therapy for HER-overexpressing tumors was associated with improved survival in BM BC patients. This subgroup of patients may benefit from innovative approaches, in order to obtain better intra cerebral control

  7. 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.

    Science.gov (United States)

    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).

  8. Brain metastases: computed tomography assessment

    International Nuclear Information System (INIS)

    Gordillo, Victoria; Yagual, Glenda; Vinueza, Clayreth

    1998-01-01

    Intracranial metastatic tumor is relatively frequent in patients with cancer from other origin. Its location and type of metastasis varies in relation to its linage from the primary tumor. And the sequence goes from the most frequent: lung and breast cancer, melanoma, GU tract, leukemia, GI tract, head and neck tumor. Computed tomography findings are extremely varied and non specific, so there are no radiologic characteristics even from the primary tumor. We reviewed 29 TC studies in the Radiology department of ION-SOLCA, from patients with diagnosis of brain metastasis, our findings showed the great variability in the radio-diagnosis imaging. (The author)

  9. 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.

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

    Science.gov (United States)

    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

  11. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua, E-mail: wlhwq@yahoo.com

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  12. Immunotherapy targeting immune check-point(s) in brain metastases.

    Science.gov (United States)

    Di Giacomo, Anna Maria; Valente, Monica; Covre, Alessia; Danielli, Riccardo; Maio, Michele

    2017-08-01

    Immunotherapy with monoclonal antibodies (mAb) directed to different immune check-point(s) is showing a significant clinical impact in a growing number of human tumors of different histotype, both in terms of disease response and long-term survival patients. In this rapidly changing scenario, treatment of brain metastases remains an high unmeet medical need, and the efficacy of immunotherapy in these highly dismal clinical setting remains to be largely demonstrated. Nevertheless, up-coming observations are beginning to suggest a clinical potential of cancer immunotherapy also in brain metastases, regardless the underlying tumor histotype. These observations remain to be validated in larger clinical trials eventually designed also to address the efficacy of therapeutic mAb to immune check-point(s) within multimodality therapies for brain metastases. Noteworthy, the initial proofs of efficacy on immunotherapy in central nervous system metastases are already fostering clinical trials investigating its therapeutic potential also in primary brain tumors. We here review ongoing immunotherapeutic approaches to brain metastases and primary brain tumors, and the foreseeable strategies to overcome their main biologic hurdles and clinical challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. 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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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

  15. 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

    International Nuclear Information System (INIS)

    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.

  16. Radiosurgery without whole brain radiotherapy in melanoma brain metastases

    International Nuclear Information System (INIS)

    Grob, J.J.; Regis, J.; Laurans, R.; Delaunay, M.; Wolkenstein, P.; Paul, K.; Souteyrand, P.; Koeppel, M.C.; Murraciole, X.; Perragut, J.C.; Bonerandi, J.J.

    1998-01-01

    To evaluate the effectiveness of radiosurgery without whole brain radiotherapy in the palliative treatment of melanoma brain metastases, we retrospectively assessed the results in 35 patients: 4 with a solitary brain metastasis, 13 with a single brain metastasis and metastases elsewhere and 18 with multiple brain metastases. The local control rate was 98.2% (55/56 metastases) at 3 months. Median survival was 22 months in patients with a solitary brain metastasis, 7.5 months in patients with a single brain metastasis and metastases elsewhere, and 4 months in patients with multiple brain metastases. Complications were unusual and surgery was required in 2 of 35 patients. These results show for the first time that melanoma patients with a unique brain metastasis with or without metastases elsewhere clearly benefit from tumour control easily obtained by radiosurgery. Although the comparison of radiosurgery with surgery and/or whole brain radiotherapy cannot be adequately addressed, radiosurgery alone seems to provide similar results with lower morbidity and impact on quality of life. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

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

    Science.gov (United States)

    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.

  18. Neural Stem Cell Delivery of Therapeutic Antibodies to Treat Breast Cancer Brain Metastases

    Science.gov (United States)

    2010-10-01

    Barry AM, MacKenzie LT, Mikulis DJ, Palmieri D, Bronder JL, Steeg PS, Yoneda T, MacDonald IC, Chambers AF, Rutt BK, Foster PJ: In vivo MRI of cancer...Fransisco, CA). Caspase-3 was immunoprecipitated from cell lysates in the presence of protease inhibitors (Roche complete Mini tablet , EDTA-free and 2

  19. Spine Metastases in Lung Cancer

    Directory of Open Access Journals (Sweden)

    O.Yu. Stolyarova

    2015-10-01

    Full Text Available The purpose and the objectives of the study were to determine the incidence of metastatic lesions to various parts of the spine, the assessment of the association with other clinical signs of lung cancer (localization, form, histology, degree of differentiation, staging, nature of extraosseous metastasis, to investigate the effect of these parameters on the survi­val of the patients. Material and methods. The study included 1071 patients with lung cancer aged 24 to 86 years. None of the examined patients has been operated previously for lung cancer, and after arriving at a diagnosis, all patients received radiation therapy, 73 % of them — combined radiochemothe­rapy. Results. Metastasis in the vertebral bodies and vertebral joints occurs in 13 % of patients with lung cancer and in 61 % of patients with bone form of the disease, the ratio of the defeat of thoracic, sacral, lumbar and cervical spine was 6 : 4 : 2 : 1. The development of metastases in the spine is mostly associa­ted with the localization of the tumor in the upper lobe of the lung, the peripheral form of the disease, with non-small cell histologic variants (adenocarcinoma and squamous cell carcinoma. The number of metastases in the spinal column directly correlates with the degree of metastatic involvement of the inguinal lymph nodes, abdominal wall and the liver, has an impact on the invasion of lung tumor into the esophagus and the trachea. The life expectancy of the deceased persons with spine metastases is less than that of other patients with the lung cancer, but the overall survival rate in these groups of patients is not very different. Conclusions. Clinical features of lung cancer with metastases in the spine necessitate the development of medical technology of rational radiochemotherapy in such patients.

  20. 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)

    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

  1. Delivery of Nanotethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

    Science.gov (United States)

    2016-12-01

    transport in tissue based on the acquired medical images of an individual patient (CT and MRI ) with sufficient accuracy and at accelerated rates for...anatomical and physiological information provided by imaging modalities such as CT, Ultrasound, PET, MRI , etc. In the current work we have developed a...capability to develop and optimize treatment plans for optimal release of pharmaceuticals in the treatment of cancer. Future work will test and

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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

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

    NARCIS (Netherlands)

    Meyners, Thekla; Heisterkamp, Christine; Kueter, Jan-Dirk; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.; Rades, Dirk

    2010-01-01

    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

  5. Selected Arterial Infusion Chemotherapy Combined with Target Drugs 
for Non-small Cell Lung Cancer with Multiple Brain Metastase

    Directory of Open Access Journals (Sweden)

    Jinduo LI

    2012-05-01

    Full Text Available Background and objective The aim of this study is to evaluate the efficacy of selected arterial infusion chemotherapy in treating non-small cell lung cancer (NSCLC with multiple brain metastases and corresponding factors to influencing prognosis. Methods From September 2008 to October 2011, a total of 31 patients of NSCLC with multiple brain metastases (≥3 received selected incranial, bronchial and corresponding target arterial infusion chemotherapy combined with EGFR-TKIs. Interventional treatment was performed every four weeks, two-six cycles with synchronized or sequential targeted drugs (erlotinib, gefitinib or icotinib. Follow-up CT and MRI were regularly finished at interval of four weeks after two cycles of interventional treatment were finished or during taking targeted drugs in order to evaluate efficacy of the therapy. The procedure was stopped for the tumor disease was worse or the patient could not tolerate the toxity of drugs any longer. Results 31 patients was performed two to six cycles of interventional therapy, 3cycles at average. Response assessment showed that 5 (16.1% patients got a complete response (CR, 7 (22.6% had a partial response (PR, 11 (35.5% had a stable disease (SD and 8 (25.8% had a progressive disease (PD. The objective response rate (ORR was 38.7%, and the disease control rate was 74.2%. The median progression free survival (PFS and overall survival (OS were 13.1 months and 15.1 months. The 6-month survival rate, one-year survival rate and two-year survival rate were 79%, 61.1%, and 31.1%, respectively. The patients’ OS and PFS were influenced by smoking state, tumor pathology, extracranial metastases, period of targeted drug taking and performance status, not by sex, age, before therapy and the total of brain metastases. Conclusion Selected arterial infusion chemotherapy with targeted drugs is one of the most effective and safe treatment to NSCLC with multiple brain metastases. Smoking status, tumor

  6. Surgical treatment of brain metastases - a review. Part 2. Results of treatment

    International Nuclear Information System (INIS)

    Wronski, M.; Czernicki, Z.

    1994-01-01

    Results of treatment of most frequent brain metastases from nonsmall cell lung cancer, breast cancer, malignant melanoma and kidney tumors are discussed. Also efficacy of surgical treatment, chemotherapy, radiotherapy and radiosurgery is analyzed

  7. 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.)

  8. [Guideline on brain metastases: not a cookbook].

    Science.gov (United States)

    Reijneveld, Jaap C

    2011-01-01

    The guideline 'Brain Metastases', which was revised on behalf of the Dutch Society for Neuro-Oncology (LWNO), provides an excellent overview of levels of scientific evidence on diagnosis and treatment of patients with parenchymal brain metastases of solid tumours. I would like to emphasize, however, that this guideline is not a cookbook for facilitating individual physicians to treat patients on their own. It is important that every patient suffering from brain metastases is discussed by a multidisciplinary tumour board consisting of at least a neurologist, a neurosurgeon, a medical oncologist, a radiation oncologist, a pathologist and a radiologist, and that several crucial questions need to be explicitly asked and answered about every single patient.

  9. Skin metastases from lung cancer: a case report.

    Science.gov (United States)

    Pajaziti, Laura; Hapçiu, Syzana Rexhepi; Dobruna, Shkendije; Hoxha, Naim; Kurshumliu, Fisnik; Pajaziti, Artina

    2015-04-11

    Lung cancer is one of the most frequent malignancies, with high mortality rates. It can metastasize in almost all organs, but more often invades hilar nodes, liver, adrenal glands, bones and brain. There are various data on the incidence of lung cancer metastases in the skin. In 1-12% of patients with lung cancer are developed skin metastases. Metastases in the skin may be the first sign of lung cancer. Forty-five years old Albanian male, smoker, was admitted to our department with multiple nodules localized in the skin of the head, neck, back and chest. The nodules measuring 5-15 millimeters in greatest dimension were round and skin-colored, with telangiectasias, firm and tender. They appeared in an eruptive form about two weeks before being admitted at our hospital. In addition, the patient exhibited signs of weight loss, anorexia and fatigue. Excisional biopsy was performed to one of the lesions. Histopathology confirmed metastatic nature of the lesion namely, malignant tumor of neuroendocrine phenotype consistent with small-cell carcinoma. Chest X-ray and computed tomography revealed an expansive process in the 7(th) segment of the left lung, left hilar and mediastinal lymphadenopathy and a suspicious initial secondary deposit in the left adrenal gland. The patient was referred to the department of oncology for further treatment. After the third cycle of chemotherapy, the magnetic resonance imaging revealed brain metastases. The patient passed away four months after the diagnosis of lung cancer first presented with skin metastases. Metastases in skin may be the first sign of lung cancer. Although rare appearing, we should raise suspicion in cases of atypical lesions in the skin not only of the smokers, but also of the non-smokers. Skin metastases from small-cell lung carcinoma are a poor prognostic indicator. The appearance of multiple skin metastases with other internal metastases shorten the survival time.

  10. Metastases cerebrales d'un cancer de l'endometre: a propos d'une ...

    African Journals Online (AJOL)

    Mots clés: cancer, endomètre, métastases, cerveau, Lomé, Togo. English Title: Brain metastases of endometrial cancer: an observation at Lome and literature review. English Abstract. Introduction: document the clinical, paraclinical, therapeutic and prognostic of brain metastases of endometrial cancer in hospital in Togo.

  11. Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Mao-hua Zheng

    2016-01-01

    Full Text Available Background. To comprehensively assess the efficacy and safety of whole-brain radiotherapy (WBRT combined with gefitinib/erlotinib for treatment of brain metastases (BM from non-small-cell lung cancer (NSCLC. Methods. Databases including PubMed, EMBASE.com, Web of Science, and Cochrane Library were searched from inception to April 12, 2015. Studies on randomized controlled trials (RCTs and case-control trials comparing WBRT combined with gefitinib/erlotinib versus WBRT alone for BM from NSCLC were included. Literature selection, data extraction, and quality assessment were performed independently by two trained reviewers. RevMan 5.3 software was used to analyze data. Results. A total of 7 trials involving 622 patients were included. Compared with WBRT alone or WBRT plus chemotherapy, WBRT plus gefitinib/erlotinib could significantly improve response rate (OR = 2.16, 95% CI: 1.35–3.47; P=0.001, remission rate of central nervous system (OR = 6.06, 95% CI: 2.57–14.29; P<0.0001, disease control rate (OR = 3.34, 95% CI: 1.84–6.07; P<0.0001, overall survival (HR = 0.72, 95% CI: 0.58–0.89; P=0.002, and 1-year survival rate (OR = 2.43, 95% CI: 1.51–3.91; P=0.0002. In adverse events (III-IV, statistically significant differences were not found, except for rash (OR = 7.96, 95% CI: 2.02–31.34; P=0.003 and myelosuppression (OR = 0.19, 95% CI: 0.07–0.51; P=0.0010. Conclusions. WBRT plus gefitinib/erlotinib was superior to WBRT alone and well tolerated in patients with BM from NSCLC.

  12. Therapeutic challenge in brain metastases: chemotherapy, surgery or radiotherapy

    International Nuclear Information System (INIS)

    Mena, Ivan; Contreras, Manuel; Ceballos Francisco

    1998-01-01

    Metastases to the brain occur in 25 to 35% of patients with systemic cancer. Cerebral metastatic is the most common intracranial tumor in adults and occur up to 10 times more frequently than primary tumors in the central nervous system. Significant advances have occurred in the diagnosis and treatment of metastases to the brain, and the therapeutic nihilism of the past is now no longer warranted for most patients. With the currently available treatments, most patients do not die of their brain metastases and usually experience effective palliation of neurologic symptoms and meaning full extension of life. As a trial to limit the cerebral metastatic disease, many and diverse therapy options have been developed such as: chemotherapy, surgery plus whole-brain radiotherapy, only radiation therapy, therapy with neutron, intersticial brachytherapy and stereotactic radiosurgery. In selected cases, surgery plus whole-brain radiotherapy is the conventional treatment for single metastases. However, recurrence usually limits the quality of life and greatly decrease the patients time life, and the therapy options are scarce. This piece of writing also includes a review of the available therapy forms to manage this kind of lesions. (The author)

  13. 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

  14. Neurosurgical Treatment of Breast Cancer Metastases to the Neurocranium

    Directory of Open Access Journals (Sweden)

    Andreas M. Stark

    2011-01-01

    Full Text Available Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4–11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy.

  15. Neurosurgical treatment of breast cancer metastases to the neurocranium.

    Science.gov (United States)

    Stark, Andreas M

    2010-12-16

    Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4-11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy.

  16. 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.

  17. Radiosurgery for brain metastases: is whole brain radiotherapy necessary?

    International Nuclear Information System (INIS)

    Sneed, Penny K.; Lamborn, Kathleen R.; Forstner, Julie M.; McDermott, Michael W.; Chang, Susan; Park, Elaine; Gutin, Philip H.; Phillips, Theodore L.; Wara, William M.; Larson, David A.

    1999-01-01

    Purpose: Because whole brain radiotherapy (WBRT) may cause dementia in long-term survivors, selected patients with brain metastases may benefit from initial treatment with radiosurgery (RS) alone reserving WBRT for salvage as needed. We reviewed results of RS ± WBRT in patients with newly diagnosed brain metastasis to provide background for a prospective trial. Methods and Materials: Patients with single or multiple brain metastases managed initially with RS alone vs. RS + WBRT (62 vs. 43 patients) from 1991 through February 1997 were retrospectively reviewed. The use of upfront WBRT depended on physician preference and referral patterns. Survival, freedom from progression (FFP) endpoints, and brain control allowing for successful salvage therapy were measured from the date of diagnosis of brain metastases. Actuarial curves were estimated using the Kaplan-Meier method. Analyses to adjust for known prognostic factors were performed using the Cox proportional hazards model (CPHM) stratified by primary site. Results: Survival and local FFP were the same for RS alone vs. RS + WBRT (median survival 11.3 vs. 11.1 months and 1-year local FFP by patient 71% vs. 79%, respectively). Brain FFP (scoring new metastases and/or local failure) was significantly worse for RS alone vs. RS + WBRT (28% vs. 69% at 1 year; CPHM adjusted p = 0.03 and hazard ratio = 0.476). However, brain control allowing for successful salvage of a first failure was not significantly different for RS alone vs. RS + WBRT (62% vs. 73% at 1 year; CPHM adjusted p = 0.56). Conclusions: The omission of WBRT in the initial management of patients treated with RS for up to 4 brain metastases does not appear to compromise survival or intracranial control allowing for salvage therapy as indicated. A randomized trial of RS vs. RS + WBRT is needed to assess survival, quality of life, and cost in good-prognosis patients with newly diagnosed brain metastases

  18. 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

  19. Radiotherapy management of brain metastases using conventional linear accelerator.

    Science.gov (United States)

    Matzenauer, Marcel; Vrana, David; Vlachova, Zuzana; Cwiertka, Karel; Kalita, Ondrej; Melichar, Bohuslav

    2016-09-01

    As treatments for primary cancers continue to improve life expectancy, unfortunately, brain metastases also appear to be constantly increasing and life expectancy for patients with brain metastases is low. Longer survival and improved quality of life may be achieved using localised radiological and surgical approaches in addition to low dose corticosteroids. Stereotactic brain radiotherapy is one rapidly evolving localized radiation treatment. This article describes our experience with stereotactic radiotherapy using a linear accelerator. We reviewed patients treated with stereotactic radiotherapy, from the time of its introduction into daily practice in our Department of Oncology in 2014. We collected the data on patient treatment and predicted survival based on prognostic indices and actual patient outcome. A total of 10 patients were treated by stereotactic radiotherapy, in one case in combination with whole brain radiotherapy and hippocampal sparing. There was no significant treatment related toxicity during the treatment or follow-up and due to the small number of fractions, the overall tolerance of the treatment was excellent. The patient intrafractional movement in all cases was under 1 mm suggesting that 1 mm margin around the CTV to create the PTV is sufficient and also that patient immobilization using the thermoplastic mask compared with invasive techniques, is feasible. We also found that prognostic indices such as the Graded Prognostic Assessment provide accurate predictions of patient survival. Based on our current evidence, patients with brain metastases fit enough, should be considered for stereotactic radiotherapy treatment.

  20. Radiosurgery for brain metastases: the Tuebingen experience

    International Nuclear Information System (INIS)

    Becker, Gerd; Jeremic, Branislav; Engel, Corinna; Buchgeister, Markus; Paulsen, Frank; Duffner, Frank; Meisner, Christoph; Bamberg, Michael

    2002-01-01

    Purpose: To retrospectively investigate the effectiveness of linear accelerator based radiosurgery (RS) in the treatment of brain metastases (BM). Material and methods: Of 55 patients with a total of 72 BM, 41 patients had a single brain metastasis and 14 patients had two or three metastases. Median tumour dose of 15 Gy (range 8-20 Gy) was prescribed to a median isodose surface of 90% (range 70-100%) encompassing the target volume. Results: The median survival time (MST) for all 55 patients was 7 months [95% confidence interval (CI), 5-10 months] and 2-year survival is 18%. There was no significant difference between patients who had one brain metastasis and those with either two or three metastases (log rank P=0.7565). Multivariate analysis in patients with a single BM showed that interval between primary diagnosis (PD) to BM, maximum size of metastasis, and histology (renal cell carcinoma and melanoma versus others) were independent prognostic factors influencing survival. Local control was obtained in 66/72 (92%) metastases. Actuarial local control at 24 months was 52%. Only age (≤50 years vs >50 years) and histology (renal cell versus others) influenced local control in the univariate analysis in patients with a single BM. In multivariate analysis, size, histology (renal cell and melanoma versus others), activity of extracranial metastatic disease, age, interval from PD to BM and location (midline versus other) independently influenced local control, while the dose was not significant for our patient group. Only one patient developed radiographically suspected RS-induced necrosis after previous whole brain RT. Conclusion: RS was effective and little toxic in BM. Identification of prognostic factors must be performed to gain knowledge on patients most likely to benefit from this procedure

  1. Brain Metastases Treatment Worsens Cognitive Decline

    Science.gov (United States)

    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.

  2. Radiosurgery for brain metastases: is whole brain radiation therapy necessary?

    International Nuclear Information System (INIS)

    Forstner, Julie M.; Sneed, Penny K.; Lamborn, Kathleen R.; Shu, H.-K.G.; McDermott, Michael W.; Park, Elaine; Ho, Maria; Chang, Susan; Gutin, Philip H.; Phillips, Theodore L.; Wara, William M.; Larson, David A.

    1996-01-01

    Purpose: Because whole brain radiotherapy (WBRT) carries a significant risk of dementia in long-term survivors, it is desirable to determine if some patients with brain metastases may be managed with radiosurgery (RS) alone, reserving WBRT for salvage therapy as needed. To begin to approach this problem, we retrospectively reviewed freedom from brain failure/progression (Brain FFP) and survival of patients with newly-diagnosed solitary or multiple brain metastases treated with Gamma Knife RS ± WBRT. Materials and Methods: All patients treated at our institution with Gamma Knife RS for newly-diagnosed solitary or multiple (2-8) brain metastases from September 1991 through December 1995 were reviewed. Whether or not WBRT was given depended on physician preference and referral patterns. Brain FFP was measured from the date of RS until development of a new brain metastasis or progression of a treated metastasis, with censoring at the time of the last imaging study. Survival was measured from the date of RS until death or last clinical follow-up. Actuarial curves were estimated using the Kaplan-Meier method and compared with the log rank test. Multivariate analyses to adjust for known prognostic variables (age, KPS, history of extracranial metastases, and total target volume) were performed using the Cox proportional hazards model. Results: From September 1991-December 1995, 90 patients with newly-diagnosed brain metastases underwent RS. Three patients treated palliatively to a small component of their intracranial disease were excluded, leaving 54 treated with RS alone and 33 treated with RS + WBRT. Age ranged from 31-83 years (median, 59 years), KPS from 60-100 (median, 90), and total target volume from 0.15-26.1 cm 3 (median, 5.5 cm 3 ). Fifty patients had a history of extracranial metastases. Results are shown below. In the RS alone group, (22(54)) patients (41%) had a brain failure and (20(54)) (37%) died without evidence of brain failure. In the RS + WBRT group

  3. Therapeutic Effect of Gamma Knife Radiosurgery for Multiple Brain Metastases

    Science.gov (United States)

    Lee, Chul-Kyu; Lee, Sang Ryul; Cho, Jin Mo; Yang, Kyung Ah

    2011-01-01

    Objective The aim of this study is to evaluate the therapeutic effects of gamma knife radiosurgery (GKRS) in patients with multiple brain metastases and to investigate prognostic factors related to treatment outcome. Methods We retrospectively reviewed clinico-radiological and dosimetric data of 36 patients with 4-14 brain metastases who underwent GKRS for 264 lesions between August 2008 and April 2011. The most common primary tumor site was the lung (n=22), followed by breast (n=7). At GKRS, the median Karnofsky performance scale score was 90 and the mean tumor volume was 1.2 cc (0.002-12.6). The mean prescription dose of 17.8 Gy was delivered to the mean 61.1% isodose line. Among 264 metastases, 175 lesions were assessed for treatment response by at least one imaging follow-up. Results The overall median survival after GKRS was 9.1±1.7 months. Among various factors, primary tumor control was a significant prognostic factor (11.1±1.3 months vs. 3.3±2.4 months, p=0.031). The calculated local tumor control rate at 6 and 9 months after GKRS were 87.9% and 84.2%, respectively. Paddick's conformity index (>0.75) was significantly related to local tumor control. The actuarial peritumoral edema reduction rate was 22.4% at 6 months. Conclusion According to our results, GKRS can provide beneficial effect for the patients with multiple (4 or more) brain metastases, when systemic cancer is controlled. And, careful dosimetry is essential for local tumor control. Therefore, GKRS can be considered as one of the treatment modalities for multiple brain metastase. PMID:22102945

  4. 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

  5. Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

    Science.gov (United States)

    2015-12-01

    empirical method was developed to simulate photon transport in tissue based on the acquired medical images of an individual patient (CT and MRI ) with... MRI , etc. In the current work we have developed a fast voxel based empirical approach which can estimate photon fluence in the brain and evaluate...These tools provide the capability to develop and optimize treatment plans for optimal release of pharmaceuticals to metastatic breast cancer in the

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

    International Nuclear Information System (INIS)

    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)

  7. Radiotherapy for brain metastases: defining palliative response

    International Nuclear Information System (INIS)

    Bezjak, Andrea; Adam, Janice; Panzarella, Tony; Levin, Wilfred; Barton, Rachael; Kirkbride, Peter; McLean, Michael; Mason, Warren; Wong, Chong Shun; Laperriere, Normand

    2001-01-01

    Background and purpose: Most patients with brain metastases are treated with palliative whole brain radiotherapy (WBRT). There is no established definition of palliative response. The aim of this study was to develop and test clinically useful criteria for response following palliative WBRT. Materials and methods: A prospective study was conducted of patients with symptomatic brain metastases treated with WBRT (20 Gy/5 fractions) and standardised steroid tapering. Assessments included observer rating of neurological symptoms, patient-completed symptom checklist and performance status (PS). Response criteria were operationally defined based on a combination of neurological symptoms, PS and steroid dose. Results: Seventy-five patients were accrued. At 1 month, presenting neurological symptoms were improved in 14 patients, stable in 17, and worse in 21; 23 patients were not assessed, mainly due to death or frailty. Using response criteria defined a priori, 15% (95% CI 7-23%) of patients were classified as having a response to RT, 25% no response, and 29% progression; 27% were deceased at or soon after 1 month. A revised set of criteria was tested, with less emphasis on complete tapering of steroids: they increased the proportion of patients responding to 39% (95% CI 27-50%) but didn't change the large proportion who did not benefit (44%). Conclusions: Clinical response to RT of patients with brain metastases is multifactorial, comprising symptoms, PS and other factors. Assessment of degree of palliation depend on the exact definition used. More research is needed in this important area, to help validate criteria for assessing palliation after WBRT

  8. Role of the Blood-Brain Barrier in the Formation of Brain Metastases

    Directory of Open Access Journals (Sweden)

    István A. Krizbai

    2013-01-01

    Full Text Available The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma. In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier (BBB. The BBB has a dual role in brain metastasis formation: it forms a tight barrier protecting the central nervous system from entering cancer cells, but it is also actively involved in protecting metastatic cells during extravasation and proliferation in the brain. The mechanisms of interaction of cancer cells and cerebral endothelial cells are largely uncharacterized. Here, we provide a comprehensive review on our current knowledge about the role of junctional and adhesion molecules, soluble factors, proteolytic enzymes and signaling pathways mediating the attachment of tumor cells to brain endothelial cells and the transendothelial migration of metastatic cells. Since brain metastases represent a great therapeutic challenge, it is indispensable to understand the mechanisms of the interaction of tumor cells with the BBB in order to find targets of prevention of brain metastasis formation.

  9. 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...

  10. Whole brain radiotherapy with radiosensitizer for brain metastases

    Directory of Open Access Journals (Sweden)

    Viani Gustavo

    2009-01-01

    Full Text Available Abstract Purpose To study the efficacy of whole brain radiotherapy (WBRT with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment. Methods A meta-analysis of randomized controlled trials (RCT was performed in order to compare WBRT with radiosensitizer for brain metastases and WBRT alone. The MEDLINE, EMBASE, LILACS, and Cochrane Library databases, in addition to Trial registers, bibliographic databases, and recent issues of relevant journals were researched. Significant reports were reviewed by two reviewers independently. Results A total of 8 RCTs, yielding 2317 patients were analyzed. Pooled results from this 8 RCTs of WBRT with radiosensitizer have not shown a meaningful improvement on overall survival compared to WBRT alone OR = 1.03 (95% CI0.84–1.25, p = 0.77. Also, there was no difference in local brain tumor response OR = 0.8(95% CI 0.5 – 1.03 and brain tumor progression (OR = 1.11, 95% CI 0.9 – 1.3 when the two arms were compared. Conclusion Our data show that WBRT with the following radiosentizers (ionidamine, metronidazole, misonodazole, motexafin gadolinium, BUdr, efaproxiral, thalidomide, have not improved significatively the overall survival, local control and tumor response compared to WBRT alone for brain metastases. However, 2 of them, motexafin- gadolinium and efaproxiral have been shown in recent publications (lung and breast to have positive action in lung and breast carcinoma brain metastases in association with WBRT.

  11. Could new reconstruction CT techniques challenge MRI for the detection of brain metastases in the context of initial lung cancer staging?

    Energy Technology Data Exchange (ETDEWEB)

    Millon, Domitille; Byl, David; Coche, Emmanuel E. [Universite Catholique de Louvain, Department of Radiology and Medical Imaging, Cliniques Universitaires Saint Luc, Brussels (Belgium); Collard, Philippe [Universite Catholique de Louvain, Department of Pneumology, Cliniques Universitaires Saint Luc, Brussels (Belgium); Cambier, Samantha E.; Maanen, Aline G. van [Universite Catholique de Louvain, Statistic Unit, King Albert II Cancer Institute, Brussels (Belgium); Vlassenbroek, Alain [Philips Healthcare, Brussels (Belgium)

    2018-02-15

    To evaluate the diagnostic performance of brain CT images reconstructed with a model-based iterative algorithm performed at usual and reduced dose. 115 patients with histologically proven lung cancer were prospectively included over 15 months. Patients underwent two CT acquisitions at the initial staging, performed on a 256-slice MDCT, at standard (CTDIvol: 41.4 mGy) and half dose (CTDIvol: 20.7 mGy). Both image datasets were reconstructed with filtered back projection (FBP) and iterative model-based reconstruction (IMR) algorithms. Brain MRI was considered as the reference. Two blinded independent readers analysed the images. Ninety-three patients underwent all examinations. At the standard dose, eight patients presented 17 and 15 lesions on IMR and FBP CT images, respectively. At half-dose, seven patients presented 15 and 13 lesions on IMR and FBP CT images, respectively. The test could not highlight any significant difference between the standard dose IMR and the half-dose FBP techniques (p-value = 0.12). MRI showed 46 metastases on 11 patients. Specificity, negative and positive predictive values were calculated (98.9-100 %, 93.6-94.6 %, 75-100 %, respectively, for all CT techniques). No significant difference could be demonstrated between the two CT reconstruction techniques. (orig.)

  12. 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

  13. 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.

    Science.gov (United States)

    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

  14. 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.

  15. Innovative Therapeutic Strategies in the Treatment of Brain Metastases

    Directory of Open Access Journals (Sweden)

    Francesco Tomasello

    2013-01-01

    Full Text Available Brain metastases (BM are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases are associated with a poor prognosis and a poor performance status. Metastasis development involves the migration of a cancer cell from the bulk tumor into the surrounding tissue, extravasation from the blood into tissue elsewhere in the body, and formation of a secondary tumor. In the recent past, important results have been obtained in the management of patients affected by BM, using surgery, radiation therapy, or both. Conventional chemotherapies have generally produced disappointing results, possibly due to their limited ability to penetrate the blood–brain barrier. The advent of new technologies has led to the discovery of novel molecules and pathways that have better depicted the metastatic process. Targeted therapies such as bevacizumab, erlotinib, gefitinib, sunitinib and sorafenib, are all licensed and have demonstrated improved survival in patients with metastatic disease. In this review, we will report current data on targeted therapies. A brief review about brain metastatic process will be also presented.

  16. Imaging of rare radiation injuries after radiosurgery for brain metastases

    International Nuclear Information System (INIS)

    Yamanaka, Kazuhiro; Yoshimura, Masaki; Iwai, Yoshiyasu

    2011-01-01

    Gamma knife radiosurgery (GKS) is generally an effective and safe treatment for brain metastases. We report 3 rare complicated cases after GKS due to radiation injury including image findings. Case 1: A 58-year-old man received whole brain radiation therapy for right occipital brain metastasis from lung cancer. However, local recurrence was noted and GKS was carried out 5 months later (size 28 mm, marginal dose 23 Gy (50% isodose)). Four years later, a cyst appeared and the patient developed apraxia and visual disturbance. Surgery was performed and the histopathology showed necrosis. Case 2: A 51-year-old woman received GKS for 4 brain metastases from breast cancer. The right occipital lobe lesion was treated with marginal dose of 18 Gy (size 24 mm, 50% isodose). Thirty-one months later, she developed left homonymous hemianopsia and MR imaging and CT scan showed intracerebral hemorrhage with cyst formation. An operation was performed and the histology revealed necrosis. Case 3: A 37-year-old man received GKS for left temporal brain metastasis from lung cancer (size 14 mm, marginal dose 23 Gy (50% isodose)). Twelve months later, the lesion increased in size again, so we carried out a second GKS on the same lesion (size 15 mm, marginal dose 23 Gy (50% isodose)). Thirty-five months later, massive peritumoral edema appeared and the patient developed left oculomotor palsy. An emergency operation was performed and the histopathological diagnosis was cavernous malformation that was thought to be induced by radiosurgery. Although the incidence is low, rare complications associated with radiation therapy can also occur by radiosurgery. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

  18. A case of lung adenocarcinoma with multiple intracranial hemorrhages of brain metastases after whole-brain radiation therapy

    International Nuclear Information System (INIS)

    Nakamichi, Shinji; Hirano, Satoshi; Asao, Tetsuhiko; Takeda, Yuichiro; Sugiyama, Haruhito; Kobayashi, Nobuyuki

    2011-01-01

    Whole-brain radiation therapy (WBRT) is widely applied in cases of brain metastases of non-small cell lung cancer (NSCLC). However, there are few case reports on hemorrhages of brain metastases occurring after WBRT. A 63-year-old woman was given a diagnosis of stage IV (T4N0M1b) lung adenocarcinoma about 4 years previously, and received chemotherapy regimens and gamma knife radiosurgery. However, her brain metastases exacerbated and she received WBRT in November 2010 and docetaxel monotherapy in December 2010. Two weeks after completing WBRT, she experienced dysarthria and an MRI showed multiple hemorrhages within brain metastases. Over a period of careful observation, these hemorrhages repeatedly alternated between improvement and exacerbation. Radiotherapy for metastatic brain tumors is considered to suppress hemorrhagic events of brain metastases. However, multiple intracranial hemorrhages of brain metastases occurred after WBRT in the present case. The accumulation of further studies of similar cases is necessary to identify the exact mechanism of these hemorrhages. (author)

  19. Impact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases.

    Science.gov (United States)

    Magnuson, William J; Yeung, Jacky T; Guillod, Paul D; Gettinger, Scott N; Yu, James B; Chiang, Veronica L

    2016-06-01

    To perform a retrospective analysis of patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma who developed brain metastases (BM) to evaluate our hypothesis that the use of upfront EGFR-tyrosine kinase inhibitors (TKIs), and deferral of radiation therapy (RT), would result in inferior intracranial progression-free survival but similar overall survival (OS). Of 202 patients diagnosed with EGFR-mutant NSCLC between July 1, 2008, and December 31, 2014, 71 developed BM. Twenty-one patients were excluded owing to prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after whole-brain radiation therapy (WBRT)/stereotactic radiosurgery (SRS) or develop brain metastases. A prospective, multi-institutional, randomized trial of upfront EGFR-TKI with RT at intracranial progression versus upfront RT followed by EGFR-TKI is urgently needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. A phase II study of icotinib and whole-brain radiotherapy in Chinese patients with brain metastases from non-small cell lung cancer.

    Science.gov (United States)

    Fan, Yun; Huang, Zhiyu; Fang, Luo; Miao, Lulu; Gong, Lei; Yu, Haifeng; Yang, Haiyan; Lei, Tao; Mao, Weimin

    2015-09-01

    Icotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. A phase II study was conducted to evaluate the efficacy and safety of icotinib in combination with whole-brain radiotherapy (WBRT) in Chinese NSCLC patients with brain metastases (BMs); the cerebrospinal fluid (CSF)/plasma concentrations of icotinib were also investigated. Eligible patients had BMs from NSCLC, regardless of the EGFR status. Icotinib was administered at 125 mg orally 3 times/day until tumor progression or unacceptable toxicity, concurrently with WBRT (3.0 Gy per day, 5 days per week, to 30 Gy). CSF and plasma samples were collected simultaneously from 10 patients. Icotinib concentrations in the CSF and plasma were measured by high-performance liquid chromatography coupled with tandem mass spectrometry. Twenty patients were enrolled. The median follow-up time was 20.0 months. The overall response rate was 80.0%. The median progression-free survival time was 7.0 months (95% CI 1.2-13.2 months), and the median survival time (MST) was 14.6 months (95% CI 12.5-16.7 months). Of the 18 patients with known EGFR status, the MST was 22.0 months for those with an EGFR mutation and was 7.5 months for those with wild-type EGFR (P = 0.0001). The CSF concentration and penetration rate of icotinib were 11.6 ± 9.1 ng/mL and 1.4 ± 1.1%, respectively. No patient experienced ≥grade 4 toxicity. Icotinib was well tolerated in combination with WBRT and showed efficacy in patients with BMs from NSCLC. This clinical benefit was related to the presence of activating EGFR mutations.

  1. Accelerated split course regimen in the treatment of brain metastases

    International Nuclear Information System (INIS)

    Franchin, G.; Minatel, E.; Roncadin, M.; Trovo, M.G.; De Paoli, A.; Bortolus, R.; Arcicasa, M.; Boz, G.; Gobitti, C.; Grigoletto, E.; Bassignano, G.

    1988-01-01

    63 patients, with brain metastases were treated with an accelerated split course regimen; irradiation was given to the whole brain in 3 daily fractions of 160 cGy each for 5 days a week. The cycle was repeated after 2 weeks to a total dose of 4800 cGy. Male-female ratio was 3:1. Median age was 58 years. The most frequent site of primary tumor was lung (41 patients), breast in 6 patients, melanoma in 3 patients, other sites in 8 patients and unknown cancer in 5 patients. Thirty-five patients had multiple brain metastases localizations. Two patients failed to complete the scheduled treatment: one because of early death and the other by refusal of therapy during treatment. Complete remission was obtained in 4 patients and partial remission in 24 patients. The median survival time was 21 weeks. The overall response rate was 42.5%. Toxicity was not considerable. The treatment results were not influenced by the site of primary tumor or by disease spreading; only the neurologic status before radiotherapy and the response to treatment influenced survival. The results obtained are similar to those reported by others; however, with the accelerated split course regimen the treatment time was reduced and a shorter period of hospitalization was required. 36 refs.; 2 figs.; 3 tabs

  2. Stereotactic radiosurgery for newly diagnosed brain metastases. Comparison of three dose levels

    International Nuclear Information System (INIS)

    Rades, Dirk; Hornung, Dagmar; Blanck, Oliver; Martens, Kristina; Khoa, Mai Trong; Trang, Ngo Thuy; Hueppe, Michael; Terheyden, Patrick; Gliemroth, Jan; Schild, Steven E.

    2014-01-01

    Three doses were compared for local control of irradiated metastases, freedom from new brain metastases, and survival in patients receiving stereotactic radiosurgery (SRS) alone for one to three newly diagnosed brain metastases. In all, 134 patients were assigned to three groups according to the SRS dose given to the margins of the lesions: 13-16 Gy (n = 33), 18 Gy (n = 18), and 20 Gy (n = 83). Additional potential prognostic factors were evaluated: age (≤ 60 vs. > 60 years), gender, Karnofsky Performance Scale score (70-80 vs. 90-100), tumor type (non-small-cell lung cancer vs. melanoma vs. others), number of brain metastases (1 vs. 2-3), lesion size ( 24 months). For 13-16 Gy, 18 Gy, and 20 Gy, the 1-year local control rates were 31, 65, and 79 %, respectively (p [de

  3. Value of stereotactic radiosurgery in patients with multiple brain metastases

    International Nuclear Information System (INIS)

    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

  4. 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.

    Science.gov (United States)

    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

  5. 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.

    Science.gov (United States)

    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.

  6. Radiotherapy for bone metastases from cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Monzen, Yoshio; Nakanishi, Kazue; Ajimu, Akira; Morikawa, Minoru; Hayashi, Kuniaki

    1989-03-01

    The authors have investigated 6 cases of bone metastases from cervical cancer out of a total of 90 cases of metastatic bone tumors that were irradiated for relief of associated pain at the Department of Radiology, Nagasaki University Hospital from April 1977 to March 1987. In 2 of the 6 cases, a rare, delayed recurrence with paraaortic lymph node metastases was seen. An invasion to the proasmajor muscle, iliomajor muscle was demonstrated by Computed Tomography after the initiation of therapy, so that the size of the field was modified. Computed Tomography was found useful to determine the exact field size for radiotherapy of metastatic bone tumor.

  7. Bone metastases from gastric cancer. Clinical evaluation on bone scintigram

    Energy Technology Data Exchange (ETDEWEB)

    Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi [Kanazawa Univ. (Japan). School of Medicine

    1983-07-01

    We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N/sub 0/ or N/sub 1/ regional lymph node metastases, highly differentiated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone metastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer.

  8. Effects of icotinib with and without radiation therapy on patients with EGFR mutant non-small cell lung cancer and brain metastases

    OpenAIRE

    Yun Fan; Yanjun Xu; Lei Gong; luo Fang; Hongyang Lu; Jing Qin; Na Han; Fajun Xie; Guoqin Qiu; Zhiyu Huang

    2017-01-01

    EGFR-TKIs and radiation therapy (RT) are the principal treatment for patients with brain metastases (BM) and EGFR mutant NSCLC. However, the optimal use of brain RT for patients with asymptomatic BM remains undefined. A total of 152 patients were identified. 58 patients were excluded. Of the remaining 97 patients, 56 patients received upfront RT followed by icotinib, including WBRT or SRS. 41 patients received icotinib therapy alone. The mOS from diagnosis of BM was 27.0 months for the whole ...

  9. Neuropsychological testing and biomarkers in the management of brain metastases

    International Nuclear Information System (INIS)

    Baschnagel, Andrew; Wolters, Pamela L; Camphausen, Kevin

    2008-01-01

    Prognosis for patients with brain metastasis remains poor. Whole brain radiation therapy is the conventional treatment option; it can improve neurological symptoms, prevent and improve tumor associated neurocognitive decline, and prevents death from neurologic causes. In addition to whole brain radiation therapy, stereotactic radiosurgery, neurosurgery and chemotherapy also are used in the management of brain metastases. Radiosensitizers are now currently being investigated as potential treatment options. All of these treatment modalities carry a risk of central nervous system (CNS) toxicity that can lead to neurocognitive impairment in long term survivors. Neuropsychological testing and biomarkers are potential ways of measuring and better understanding CNS toxicity. These tools may help optimize current therapies and develop new treatments for these patients. This article will review the current management of brain metastases, summarize the data on the CNS effects associated with brain metastases and whole brain radiation therapy in these patients, discuss the use of neuropsychological tests as outcome measures in clinical trials evaluating treatments for brain metastases, and give an overview of the potential of biomarker development in brain metastases research

  10. Systematic Review of Brain Metastases in Patients With Non-Small-Cell Lung Cancer in the United States, European Union, and Japan.

    Science.gov (United States)

    Fenske, D Christian; Price, Gregory L; Hess, Lisa M; John, William J; Kim, Edward S

    2017-11-01

    Brain metastases (BRM) occur frequently in non-small-cell lung cancer (NSCLC) and present a substantial unmet medical need. Previous literature on global BRM prevalence, treatment patterns, costs, and outcomes typically has described a subset of these factors. The primary objective of this systematic literature review was to summarize BRM-related epidemiology, treatment patterns, costs, and survival of patients with NSCLC in the United States, European Union, and Japan. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. Literature searches were conducted in PubMed, Ovid MedLine, and Embase to identify studies published between 2003 and 2014. Peer-reviewed, English language, and human observational studies of patients with NSCLC and BRM were identified. Demographic characteristics, treatment patterns, histology subtype, costs, and survival data were extracted into Microsoft Excel and descriptively analyzed using SAS version 9.2 (SAS Institute, Inc). Of 8257 studies, 243 were eligible. Data from 46,422 patients with NSCLC and 27,907 patients with BRM were summarized. Radiation therapy was used by 70.7% (n = 19,736) of the total BRM population, followed by systemic therapy (8.9%, n = 2497), and surgery (6.1%, n = 1690). Reported median survival was 9.78 months ranging from 2.5 to 38 months. Radiation therapy had the best outcome at 10.0 months with 41.6% (n = 101) of the studies reporting the use of stereotactic radiosurgery. Highly variable median survival and treatment patterns were reported between countries. Costs and histology subtype data were not reported for most countries, highlighting the need for additional research to describe the economic burden of BRM and improve the diagnosis, prognosis, and prescription of effective therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Stereotactic Radiosurgical Treatment of Brain Metastases to the Choroid Plexus

    International Nuclear Information System (INIS)

    Siomin, Vitaly; Lin, Jennifer L.; Marko, Nicholas F.; Barnett, Gene H.; Toms, Steven A.; Chao, Samuel T.; Angelov, Lilyana; Vogelbaum, Michael A.; Navaratne, Kapila; Suh, John H.; Weil, Robert J.

    2011-01-01

    Purpose: Choroid plexus metastases (CPM) are uncommon lesions. Consequently, optimal management of CPM is uncertain. We summarize our experience with stereotactic radiosurgery (SRS) of CPM. Methods and Materials: Sixteen consecutive patients with presumed CPM treated with SRS between 1997 and 2007 were examined. Twelve were men with a median age at diagnosis of CPM of 61.9 ± 9.9 years; 14 had metastases from renal cell carcinoma (RCC). All patients had controlled primary disease at the time of treatment for CPM. Four patients with RCC and 1 with non-small-cell lung cancer had undergone whole-brain radiotherapy (WBRT) previously and 2 had received SRS to other brain metastases. The disease-free interval from the primary diagnosis to CPM diagnosis averaged 39.3 ± 46.2 months (range, 1.0-156.3). Five patients were asymptomatic; of the remaining 11, none had symptoms related to CPM. All presented with a single CPM. Results: Average maximum diameter of the CPMs was 2.0 ± 1.0 cm (range, 0.9-4.1 cm); mean volume was 2.4 ± 2.6 cm 3 (range, 0.2-9.3). Median SRS dose was 24 Gy to the 53% isodose line (range, 14-24 Gy). Survival after SRS to the CPM was 25.3 ± 23.4 months (range, 3.2-101.6). Patients in Recursive Partitioning Analysis (RPA) class I (n = 10) had improved survival compared to those in class II (n = 6), as did those with better GPA scores. There were no local failures. After SRS, 1 patient underwent WBRT, 3 patients had one, and another had two subsequent SRS treatments to other brain lesions. Of the 14 patients who have died, 11 succumbed to systemic disease progression, 2 to progressive, multifocal central nervous system disease, and 1 to systemic disease with concurrent, stable central nervous system disease. There were no complications related to SRS. Conclusions: Most CPMs are associated with RCC. SRS represents a safe and viable treatment option as primary modality for these metastases, with excellent outcomes.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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)

  14. Incidence of bone metastases and survival after a diagnosis of bone metastases in breast cancer patients.

    Science.gov (United States)

    Harries, M; Taylor, A; Holmberg, L; Agbaje, O; Garmo, H; Kabilan, S; Purushotham, A

    2014-08-01

    Bone is the most common metastatic site associated with breast cancer. Using a database of women with breast cancer treated at Guy's Hospital, London 1976-2006 and followed until end 2010, we determined incidence of and survival after bone metastases. We calculated cumulative incidence of bone metastases considering death without prior bone metastases as a competing risk. Risk of bone metastases was modelled through Cox-regression. Survival after bone metastases diagnosis was calculated using Kaplan-Meier methodology. Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean). Incidence of bone metastases was significantly higher in younger women, tumour size >5 cm, higher tumour grade, lobular carcinoma and ≥ four positive nodes, but was not affected by hormone receptor status. Median survival after bone metastases diagnosis was 2.3 years in women with bone-only metastases compared with early, and proportionately fewer patients in this group. Incidence of bone metastases has decreased but bone metastases remain a highly relevant clinical problem due to the large number of patients being diagnosed with breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. 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: ...

  16. 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: ...

  17. Cytogenetic findings in metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Bardi, G; Parada, L A; Bomme, L

    1997-01-01

    Eighteen tumor samples from 11 patients with metastatic colorectal cancer were cytogenetically analyzed after short-term culturing. Of the 13 metastases examined, 11 were from lymph nodes, 1 from the peritoneum and 1 from the lung. In 5 of the 11 patients, matched samples from the primary tumor...... colorectal carcinomas, and del(10)(q22) and add(16)(p13), which so far have not been associated with primary tumors and which may play a particular pathogenetic role in the metastatic process....

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

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

    International Nuclear Information System (INIS)

    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

  1. Discrimination of different brain metastases and primary CNS lymphomas using morphologic criteria and diffusion tensor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bette, S.; Wiestler, B.; Huber, T.; Boeckh-Behrens, T.; Zimmer, C.; Kirschke, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuroradiology; Delbridge, C. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuropathology; Meyer, B.; Gempt, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neurosurgery

    2016-12-15

    Brain metastases are a common complication of cancer and occur in about 15-40% of patients with malignancies. The aim of this retrospective study was to differentiate between metastases from different primary tumors/CNS lymphyomas using morphologic criteria, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Morphologic criteria such as hemorrhage, cysts, pattern of contrast enhancement and location were reported in 200 consecutive patients with brain metastases/primary CNS lymphomas. FA and ADC values were measured in regions of interest (ROIs) placed in the contrast-enhancing tumor part, the necrosis and the non-enhancing peritumoral region (NEPTR). Differences between histopathological subtypes of metastases were analyzed using non-parametric tests, decision trees and hierarchical clustering analysis. Significant differences were found in morphologic criteria such as hemorrhage or pattern of contrast enhancement. In diffusion measurements, significant differences between the different tumor entities were only found in ADC analyzed in the contrast-enhancing tumor part. Among single tumor entities, primary CNS lymphomas showed significantly lower median ADC values in the contrast-enhancing tumor part (ADC{sub lymphoma} 0.92 [0.83-1.07] vs. ADC{sub no} {sub lymphoma} 1.35 [1.10-1.64] P=0.001). Further differentiation between types of metastases was not possible using FA and ADC. There were morphologic differences among the main subtypes of brain metastases/CNS lymphomas. However, due to a high variability of common types of metastases and low specificity, prospective differentiation remained challenging. DTI including FA and ADC was not a reliable tool for differentiation between different histopathological subtypes of brain metastases except for CNS lymphomas showing lower ADC values. Biopsy, surgery and staging remain essential for diagnosis.

  2. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Thamm Reinhard

    2006-06-01

    Full Text Available Abstract Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical

  3. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    International Nuclear Information System (INIS)

    Nieder, Carsten; Grosu, Anca L; Astner, Sabrina; Thamm, Reinhard; Molls, Michael

    2006-01-01

    Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical implementation. A potential chemotherapy

  4. Brain metastasis from colorectal cancer

    International Nuclear Information System (INIS)

    Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

    2007-01-01

    The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)

  5. 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

  6. Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial.

    Science.gov (United States)

    Churilla, Thomas M; Ballman, Karla V; Brown, Paul D; Twohy, Erin L; Jaeckle, Kurt; Farace, Elana; Cerhan, Jane H; Anderson, S Keith; Carrero, Xiomara W; Garces, Yolanda I; Barker, Fred G; Deming, Richard; Dixon, Jesse G; Burri, Stuart H; Chung, Caroline; Ménard, Cynthia; Stieber, Volker W; Pollock, Bruce E; Galanis, Evanthia; Buckner, Jan C; Asher, Anthony L

    2017-12-01

    To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis. In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using 2 separate cut-points (≥2.0 vs <2.0 and ≥2.5 vs <2.5). A total of 126 NSCLC patients were included for analysis, with median follow-up of 14.2 months. Data for DS-GPA calculation were available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score ≥2.0, and 23.0% of patients had DS-GPA scores ≥2.5. The SRS and SRS + WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA ≥2.0 (favorable prognoses, P=.63; hazard ratio 0.86; 95% confidence interval 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA <2.0 patients (unfavorable prognoses, P=.85; hazard ratio 0.95; 95% confidence interval 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA ≥2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (P=.53). We observed no significant differences in survival according to receipt of WBRT in favorable-prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    International Nuclear Information System (INIS)

    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

  10. 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.

    Science.gov (United States)

    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.

  11. 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

  12. Effects of icotinib with and without radiation therapy on patients with EGFR mutant non-small cell lung cancer and brain metastases.

    Science.gov (United States)

    Fan, Yun; Xu, Yanjun; Gong, Lei; Fang, Luo; Lu, Hongyang; Qin, Jing; Han, Na; Xie, Fajun; Qiu, Guoqin; Huang, Zhiyu

    2017-03-23

    EGFR-TKIs and radiation therapy (RT) are the principal treatment for patients with brain metastases (BM) and EGFR mutant NSCLC. However, the optimal use of brain RT for patients with asymptomatic BM remains undefined. A total of 152 patients were identified. 58 patients were excluded. Of the remaining 97 patients, 56 patients received upfront RT followed by icotinib, including WBRT or SRS. 41 patients received icotinib therapy alone. The mOS from diagnosis of BM was 27.0 months for the whole cohort (95% CI, 23.9-30.1 months). There was no difference in OS between the RT followed by icotinib group and the icotinib alone group (31.9 vs. 27.9 months, P = 0.237), and similar results were found in the SRS subgroup (35.5 vs. 27.9 months, P = 0.12). Patients with the EGFR Del19 mutation had a longer OS than patients with the exon 21 L858R mutation (32.7 vs. 27.4, P = 0.037). Intracranial progression-free survival (PFS) was improved in the patients who received RT followed by icotinib compared to those receiving icotinib alone (22.4 vs. 13.9 months, P = 0.043). Patients with EGFR-mutant adenocarcinoma and BM treated with icotinib exhibited prolonged survival. A longer duration of intracranial control was observed with brain RT.

  13. CEREBRAL METASTASES CANCER OF THE LARYNX: TWO CASE REPORTS

    Directory of Open Access Journals (Sweden)

    N. V. Sevyan

    2013-01-01

    Full Text Available Cerebral metastases cancer of the larynx are rare and poorly understood pathology, many questions of diagnostics and treatment of this pathology remain open. In the work presents clinical cases сerebral metastases cancer of the larynx. Special attention is paid to surgical treatment in complex with chemotherapy.

  14. A Rare Case: Gastric Cancer; Involving Primery Thoracal Vertebral Metastases

    Directory of Open Access Journals (Sweden)

    Harun Arslan

    2013-06-01

    Full Text Available Primery bone metastases rarely occur in gastric cancer. Bone metastases indicate that the prognosis is bad. In that article we present a case that is diagnosed as a gastric cancer with primary bone metasteses that caused pathologic thoracal vertebral fracture seenby computer ised tomography.

  15. Multiple Cutaneous Metastases as Initial Presentation in Advanced Colon Cancer

    Directory of Open Access Journals (Sweden)

    Sudheer Nambiar

    2018-01-01

    Full Text Available Skin metastases from advanced colorectal cancer are relatively rare and occur most often when the cancer is advanced, following the spread to other organs. Cutaneous metastases occur in about 3% of advanced colorectal cancers. We present an extremely rare case of a 68-year-old woman with advanced ascending colon adenocarcinoma that presented with multiple rapidly progressing painless cutaneous metastatic lesions with no other distant metastases. Of all the tumors, breast cancer most commonly spreads as cutaneous metastasis is followed by lung, colorectal, renal, ovarian, and bladder cancers. Cutaneous metastases can present in a variety of clinical manifestations, such as a rapidly growing painless dermal or subcutaneous nodule with intact overlying epidermis or as ulcers. In cases where the cutaneous deposit is isolated, as in visceral metastasis, there is a role for radical management such as wide local excision and reconstruction. In our patient, since she had multiple cutaneous metastases she began treatment with palliative systemic combination chemotherapy.

  16. Retrospective study on therapy options of brain metastases: surgery versus stereotactic radiotherapy with the linear accelerator

    International Nuclear Information System (INIS)

    Fortunati, M.K.S.

    2001-04-01

    Background: in the therapy of brain metastases there has been a great progress in the last years. It was shown, that more aggressive therapies can not only extend the survival of the patients, but also improve quality of life. The major question of this study was, whether surgery or stereotactic radiotherapy with the linear accelerator show better results in behalf of the survival. Beside this major question many parameters regarding the patient or his primary cancer were examined. Methods: from the 1st of January 1995 until the 30th of June 2000 233 patients with one or more brain metastases have been treated in the Wagner Jauregg Landesnervenkrankenhaus Oberoesterreich (WJ LNKH OeO). The LINAC has been established on the 1st of July 1997. The patients have been distributed in three groups: 1. LINAC-group: 81 patients have been treated from the 1st of July 1997 until the 30th of June 2000 with the LINAC. 2. Surgery-group: 81 patients have been operated from the 1st of July 1997 until the 30th June 2000. 3 Control-group: 71 patients have been operated from the 1st of January 1995 until the 30th of June 1997, before the LINAC has been established on the 1st of July 1997. Results: There are shown the mean survival times. Therapy options (0,05): LINAC-group: 377 days. Surgery-group: 195 days. Control-group: 285 days. Primary cancer (0,05): unknown primary: 203 days. Cancer of the colon tract: 218 days. Breast cancer: 314 days. Melanoma: 162 days. Kidney: 466 days. Lung 261 days. Others: 439 days. Metastases in one/in both hemispheres (0,05): in one hemisphere 310 days, in both 184 days. All the other parameters (age, sex, Karnofsky-Index, period between diagnose of the primary and the brain metastases, primary cancer therapy, extra cerebral metastases, number of metastases, localization of metastases supra- or infratentoriell, dose/effect relationship in the LINAC-group, whole brain radiotherapy) showed interesting differences, but the results were not statistically

  17. Whole-brain radiation therapy for brain metastases: detrimental or beneficial?

    International Nuclear Information System (INIS)

    Gemici, Cengiz; Yaprak, Gokhan

    2015-01-01

    Stereotactic radiosurgery is frequently used, either alone or together with whole-brain radiation therapy to treat brain metastases from solid tumors. Certain experts and radiation oncology groups have proposed replacing whole-brain radiation therapy with stereotactic radiosurgery alone for the management of brain metastases. Although randomized trials have favored adding whole-brain radiation therapy to stereotactic radiosurgery for most end points, a recent meta-analysis demonstrated a survival disadvantage for patients treated with whole-brain radiation therapy and stereotactic radiosurgery compared with patients treated with stereotactic radiosurgery alone. However the apparent detrimental effect of adding whole-brain radiation therapy to stereotactic radiosurgery reported in this meta-analysis may be the result of inhomogeneous distribution of the patients with respect to tumor histologies, molecular histologic subtypes, and extracranial tumor stages between the groups rather than a real effect. Unfortunately, soon after this meta-analysis was published, even as an abstract, use of whole-brain radiation therapy in managing brain metastases has become controversial among radiation oncologists. The American Society of Radiation Oncology recently recommended, in their “Choose Wisely” campaign, against routinely adding whole-brain radiation therapy to stereotactic radiosurgery to treat brain metastases. However, this situation creates conflict for radiation oncologists who believe that there are enough high level of evidence for the effectiveness of whole-brain radiation therapy in the treatment of brain metastases

  18. Cerebral control and survival after stereotactic radiotherapy of brain metastases

    International Nuclear Information System (INIS)

    Arnold, Elmar Till

    2014-01-01

    This retrospective study, including 275 patients who underwent stereotactic radiotherapy due to brain metastases between 2003 and 2008, investigates influencing factors regarding cerebral control and survival, symptomatic effects and a potential benefit for patients older than 70 years. We were able to identify risk factors for remote brain failure which leads to a therapeutic recommendation. Furthermore we confirm a positive symptomatic effect and a benefit of stereotactic readiotherapy for patients over 70 years.

  19. Radiation-induced dementia in patients cured of brain metastases

    International Nuclear Information System (INIS)

    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

  20. Impact of Deferring Radiation Therapy in Patients With Epidermal Growth Factor Receptor–Mutant Non-Small Cell Lung Cancer Who Develop Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Magnuson, William J., E-mail: william.magnuson@yale.edu [Department of Radiation Oncology, Yale School of Medicine, New Haven, Connecticut (United States); Yeung, Jacky T. [Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut (United States); Guillod, Paul D. [Yale School of Medicine, New Haven, Connecticut (United States); Gettinger, Scott N. [Department of Medical Oncology, Yale School of Medicine, New Haven, Connecticut (United States); Yu, James B. [Department of Radiation Oncology, Yale School of Medicine, New Haven, Connecticut (United States); Chiang, Veronica L. [Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut (United States)

    2016-06-01

    Purpose: To perform a retrospective analysis of patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma who developed brain metastases (BM) to evaluate our hypothesis that the use of upfront EGFR–tyrosine kinase inhibitors (TKIs), and deferral of radiation therapy (RT), would result in inferior intracranial progression-free survival but similar overall survival (OS). Methods and Materials: Of 202 patients diagnosed with EGFR-mutant NSCLC between July 1, 2008, and December 31, 2014, 71 developed BM. Twenty-one patients were excluded owing to prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after whole-brain radiation therapy (WBRT)/stereotactic radiosurgery (SRS) or <6 months' follow-up. Of the remaining 50 patients, 17 received upfront EGFR-TKI followed by SRS or WBRT, 17 WBRT then EGFR-TKI, and 16 SRS followed by EGFR-TKI. Disease-specific-graded prognostic assessment was similar among all 3 groups. Results: The median OS was longer in the upfront RT group compared with the upfront EGFR-TKI group (34.1 vs 19.4 months; P=.01). On subgroup analysis, the SRS group had longer OS than the upfront EGFR-TKI group (58.4 vs 19.4 months; P=.01), but the WBRT group did not (29.9 vs 19.4 months; P=.09). Intracranial progression-free survival was improved in patients receiving upfront RT compared with those receiving upfront EGFR-TKI (37.9 vs 10.6 months; P<.001). Conclusions: The present study suggests that the use of upfront EGFR-TKI, and the deferral of SRS or WBRT, may result in inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. A prospective, multi-institutional, randomized trial of upfront EGFR-TKI with RT at intracranial progression versus upfront RT followed by EGFR-TKI is urgently needed.

  1. Radiosurgery for brain metastases: a score index for predicting prognosis

    International Nuclear Information System (INIS)

    Weltman, Eduardo; Salvajoli, Joao Victor; Brandt, Reynaldo Andre; Morais Hanriot, Rodrigo de; Prisco, Flavio Eduardo; Cruz, Jose Carlos; Oliveira Borges, Sandra Regina de; Wajsbrot, Dalia Ballas

    2000-01-01

    Purpose: To analyze a prognostic score index for patients with brain metastases submitted to stereotactic radiosurgery (the Score Index for Radiosurgery in Brain Metastases [SIR]). Methods and Materials: Actuarial survival of 65 brain metastases patients treated with radiosurgery between July 1993 and December 1997 was retrospectively analyzed. Prognostic factors included age, Karnofsky performance status (KPS), extracranial disease status, number of brain lesions, largest brain lesion volume, lesions site, and receiving or not whole brain irradiation. The SIR was obtained through summation of the previously noted first five prognostic factors. Kaplan-Meier actuarial survival curves for all prognostic factors, SIR, and recursive partitioning analysis (RPA) (RTOG prognostic score) were calculated. Survival curves of subsets were compared by log-rank test. Application of the Cox model was utilized to identify any correlation between prognostic factors, prognostic scores, and survival. Results: Median overall survival from radiosurgery was 6.8 months. Utilizing univariate analysis, extracranial disease status, KPS, number of brain lesions, largest brain lesion volume, RPA, and SIR were significantly correlated with prognosis. Median survival for the RPA classes 1, 2, and 3 was 20.19 months, 7.75 months, and 3.38 months respectively (p = 0.0131). Median survival for patients, grouped under SIR from 1 to 3, 4 to 7, and 8 to 10, was 2.91 months, 7.00 months, and 31.38 months respectively (p = 0.0001). Using the Cox model, extracranial disease status and KPS demonstrated significant correlation with prognosis (p 0.0001 and 0.0004 respectively). Multivariate analysis also demonstrated significance for SIR and RPA when tested individually (p = 0.0001 and 0.0040 respectively). Applying the Cox Model to both SIR and RPA, only SIR reached independent significance (p = 0.0004). Conclusions: Systemic disease status, KPS, SIR, and RPA are reliable prognostic factors for patients

  2. 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...

  3. Melanoma brain metastases presenting as delirium: a case report

    Directory of Open Access Journals (Sweden)

    Sofia Morais

    Full Text Available Abstract Background Metastatic tumours sometimes present with neuropsychiatric symptoms, however psychiatric symptoms as rarely the first clinical manifestation. Cutaneous melanoma is the third most common cause of brain metastasis, with known risk factors increasing the chance of such central nervous system metastization. Objectives We present a clinical report of delirium as the first clinical manifestation of melanoma brain metastases, illustrating the relevance of an adequate and early differential diagnosis. Methods In addition to describing the clinical case, searches were undertaken in PubMed and other databases using keywords such as “brain metastasis”, “melanoma”, “agitation”, “psychiatric” and “delirium”. Results We here report the case of a 52-year-old female patient evaluated by Liaison Psychiatry after sudden onset of delirium while admitted at the Gastroenterology Department to study a hypothesis of pancreatitis. A head CT scan identified brain metastases, and after further examination, including brain biopsy, melanoma brain metastization was confirmed. Discussion Some of the diagnostic challenges of psychiatric symptoms associated with secondary brain tumours are discussed, underlining the importance of an adequate differential diagnosis when working in Psychiatry Liaison.

  4. Stereotactic Radiosurgery in the Management of Brain Metastases: An Institutional Retrospective Analysis of Survival

    International Nuclear Information System (INIS)

    Frazier, James L.; Batra, Sachin; Kapor, Sumit; Vellimana, Ananth; Gandhi, Rahul; Carson, Kathryn A.; Shokek, Ori; Lim, Michael; Kleinberg, Lawrence; Rigamonti, Daniele

    2010-01-01

    Purpose: The objective of this study was to report our experience with stereotactic radiosurgery performed with the Gamma Knife (GK) in the treatment of patients with brain metastases and to compare survival for those treated with radiosurgery alone with survival for those treated with radiosurgery and whole-brain radiotherapy. Methods and Materials: Prospectively collected demographic and clinical characteristics and treatment and survival data on 237 patients with intracranial metastases who underwent radiosurgery with the GK between 2003 and 2007 were reviewed. Kaplan-Meier and Cox proportional hazards regression analyses were used to compare survival by demographic and clinical characteristics and treatment. Results: The mean age of the patient population was 56 years. The most common tumor histologies were non-small-cell lung carcinoma (34.2%) and breast cancer (13.9%). The median overall survival time was 8.5 months from the time of treatment. The median survival times for patients with one, two/three, and four or more brain metastases were 8.5, 9.4, and 6.7 months, respectively. Patients aged 65 years or greater and those aged less than 65 years had median survival times of 7.8 and 9 months, respectively (p = 0.008). The Karnofsky Performance Score (KPS) at the time of treatment was a significant predictor of survival: those patients with a KPS of 70 or less had a median survival of 2.9 months compared with 10.3 months (p = 0.034) for those with a KPS of 80 or greater. There was no statistically significant difference in survival between patients treated with radiosurgery alone and those treated with radiosurgery plus whole-brain radiotherapy. Conclusions: Radiosurgery with the GK is an efficacious treatment modality for brain metastases. A KPS greater than 70, histology of breast cancer, smaller tumor volume, and age less than 65 years were associated with a longer median survival in our study.

  5. Multiple brain metastases irradiation with Eleka Axesse stereotactic system

    Science.gov (United States)

    Filatov, P. V.; Polovnikov, E. S.; Orlov, K. Yu.; Krutko, A. V.; Kirilova, I. A.; Moskalev, A. V.; Filatova, E. V.; Zheravin, A. A.

    2017-09-01

    Brain metastases are one of the factors complicating the treatment of a malignant tumor. Radiation therapy, especially radiosurgery, plays an important role in the modern treatment practice. During 2011-2016, 32 patients (from 29 to 67 years old) with multiple brain metastases underwent the treatment with SRS or SRT in our center. The number of secondary lesions varied from 2 to 11. Eight patients underwent microsurgery resection. Seven patients had recurrence after whole brain radiotherapy. Thirty patient underwent single fraction SRS and two patients with large metastases (bigger than 3 cm) underwent fractionated SRT. The treatment was done with dedicated linear accelerator stereotactic system Elekta Axesse (Elekta AB, Stockholm, Sweden). Different stereotactic fixation devices were used, namely, Leksell G frame, non-invasive HeadFIX frame, and reinforced thermoplastic mask (IMRT perforation). All treatments included a volumetric modulated arc therapy (VMAT) technique and of Inage Guided Radiation Therapy (IGRT) technique. All lesions were treated from a single isocenter, which allowed reducing the treatment time and overall dose to the patient's body. All patients suffered the treatment satisfactorily. No adverse reactions or complications were met in any case during or right after the treatment. Different stereotactic fixation devices and modern treatment techniques allowed creating an optimal, safe and comfortable way for patient treatment. The treatment time was from 15 to 50 minutes. Patient position verification after or during the treatment demonstrated good accuracy for all fixation types and low level of intrafraction motion.

  6. Viral Immunotherapy to Eradicate Subclinical Brain Metastases

    Science.gov (United States)

    2014-05-01

    flash frozen brain tissue. Hoechst and CFSE labeled cells are readily visualized in fresh CSF. The brightest staining is achieved with Hoechst and is...viral infection in the meninges is in part due to reduction of the effects of suppressor macrophages. The work is complicated by the fact that...therapeutic effect of viral infection in the meninges is in part due to reduction of the effects of suppressor macrophages. • We found that mice cured

  7. SURGICAL TREATMENT FOR BONE METASTASES OF KIDNEY CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Semkov

    2010-01-01

    Full Text Available The data of 67 kidney cancer (KC patients with bone metastases, who had been treated at Moscow City Cancer Hospital Sixty-Two in 2002 to 2009 and had undergone skeletal bone surgery, were retrospectively analyzed. The role of surgical treatment for bone metastases from KC was assessed and the factors influencing the patients survival were determined. Surgical treatment for bone metastases from KC was ascertained to yield satisfactory results in improving the quality of life and increasing survival rates in the patients.

  8. SURGICAL TREATMENT FOR BONE METASTASES OF KIDNEY CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Semkov

    2014-08-01

    Full Text Available The data of 67 kidney cancer (KC patients with bone metastases, who had been treated at Moscow City Cancer Hospital Sixty-Two in 2002 to 2009 and had undergone skeletal bone surgery, were retrospectively analyzed. The role of surgical treatment for bone metastases from KC was assessed and the factors influencing the patients survival were determined. Surgical treatment for bone metastases from KC was ascertained to yield satisfactory results in improving the quality of life and increasing survival rates in the patients.

  9. Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.

    Science.gov (United States)

    Patil, Chirag G; Pricola, Katie; Sarmiento, J Manuel; Garg, Sachin K; Bryant, Andrew; Black, Keith L

    2017-09-25

    Historically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high-dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding SRS to WBRT is unclear. This is an updated version of the original Cochrane Review published in Issue 9, 2012. To assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of adults with brain metastases. For the original review, in 2009 we searched the following electronic databases: CENTRAL, MEDLINE, Embase, and CancerLit in order to identify trials for inclusion in this review. For the first update the searches were updated in May 2012.For this update, in May 2017 we searched CENTRAL, MEDLINE, and Embase in order to identify trials for inclusion in the review. We restricted the review to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus WBRT alone for upfront treatment of adults with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer. We used the generic inverse variance method, random-effects model in Review Manager 5 for the meta-analysis. We identified three studies and one abstract for inclusion but we could only include two studies, with a total of 358 participants in a meta-analysis. This found no difference in overall survival (OS) between the WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.65 to 1.02; 2 studies, 358 participants; moderate-quality evidence). For participants with one brain metastasis median survival was significantly longer in the WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Participants in the WBRT plus SRS group had decreased local failure compared to participants who received WBRT alone (HR 0.27, 95% CI 0.14 to 0.52; 2 studies, 129 participants; moderate-quality evidence). Furthermore, we observed an improvement in

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

    Science.gov (United States)

    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.

  11. Racial disparities in the development of breast cancer metastases among older women: a multilevel study.

    Science.gov (United States)

    Schootman, Mario; Jeffe, Donna B; Gillanders, William E; Aft, Rebecca

    2009-02-15

    Distant metastases are the most common and lethal type of breast cancer relapse. The authors examined whether older African American breast cancer survivors were more likely to develop metastases compared with older white women. They also examined the extent to which 6 pathways explained racial disparities in the development of metastases. The authors used 1992-1999 Surveillance, Epidemiology, and End Results (SEER) data with 1991-1999 Medicare data. They used Medicare's International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify metastases of respiratory and digestive systems, brain, bone, or other unspecified sites. The 6 pathways consisted of patient characteristics, tumor characteristics, type of treatment received, access to medical care, surveillance mammography use, and area-level characteristics (poverty rate and percentage African American) and were obtained from the SEER or Medicare data. Of the 35,937 women, 10.5% developed metastases. In univariate analysis, African American women were 1.61 times (95% confidence interval [CI], 1.54-1.83) more likely to develop metastasis than white women. In multivariate analysis, tumor grade, stage at diagnosis, and census-tract percentage African American explained why African American women were more likely to develop metastases than white women (hazard ratio, 0.84; 95% CI, 0.68-1.03). Interventions to reduce late-stage breast cancer among African Americans also may reduce racial disparities in subsequent increased risk of developing metastasis. African Americans diagnosed with high-grade breast cancer could be targeted to reduce their risk of metastasis. Future studies should identify specific reasons why the racial distribution in census tracts was associated with racial disparities in the risk of breast cancer metastases. (c) 2009 American Cancer Society.

  12. Unsanctifying the sanctuary: challenges and opportunities with brain metastases.

    Science.gov (United States)

    Puhalla, Shannon; Elmquist, William; Freyer, David; Kleinberg, Lawrence; Adkins, Chris; Lockman, Paul; McGregor, John; Muldoon, Leslie; Nesbit, Gary; Peereboom, David; Smith, Quentin; Walker, Sara; Neuwelt, Edward

    2015-05-01

    While the use of targeted therapies, particularly radiosurgery, has broadened therapeutic options for CNS metastases, patients respond minimally and prognosis remains poor. The inability of many systemic chemotherapeutic agents to penetrate the blood-brain barrier (BBB) has limited their use and allowed brain metastases to become a burgeoning clinical challenge. Adequate preclinical models that appropriately mimic the metastatic process, the BBB, and blood-tumor barriers (BTB) are needed to better evaluate therapies that have the ability to enhance delivery through or penetrate into these barriers and to understand the mechanisms of resistance to therapy. The heterogeneity among and within different solid tumors and subtypes of solid tumors further adds to the difficulties in determining the most appropriate treatment approaches and methods of laboratory and clinical studies. This review article discusses therapies focused on prevention and treatment of CNS metastases, particularly regarding the BBB, and the challenges and opportunities these therapies present. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Current management of liver metastases of colon cancer

    International Nuclear Information System (INIS)

    Mainieri Breedy, Giovanna

    2010-01-01

    Colon cancer has been one of the major tumors in the world, both men and women; and it is constituted the third most commonly diagnosed tumor, with approximately 1.2 million of new cases per year. This cancer type is considered of great importance in Costa Rica and has occupied the fifth place. Age is the main risk factor, followed by environmental, diabetic and genetic factors. An IV colon cancer has been manifested with any T, with any N and metastases. Metastases from colon cancer to liver can be classified according to whether have been synchronous (20 to 25%) or metachronous (15 to 29%). In turn, they can be synchronous, resectable or unresectable or mechanical resectable or unresectable. The liver has been the most common site of metastases, and the status of this organ has been an important determinant of overall survival in patients with advanced disease. Half of the patients developed metastases during the course of the disease. Metastases has represented the leading cause of death from this tumor. With the advent of new surgical techniques, new anesthetic care, new chemotherapeutic and molecular agents, together with new radiofrequency modalities and ablative treatment, the approach of metastases from colon cancer to the liver has been shown to be decisive in the prolongation of survival of the patient, who in the past was considered a terminal patient [es

  14. Volumetric Radiosurgery for 1 to 10 Brain Metastases: A Multicenter, Single-Arm, Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Nichol, Alan, E-mail: anichol@bccancer.bc.ca [Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Ma, Roy [Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Hsu, Fred [University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, BC Cancer Agency, Abbotsford Centre, Abbotsford, British Columbia (Canada); Gondara, Lovedeep [Department of Surveillance and Outcomes, BC Cancer Agency, Vancouver, British Columbia (Canada); Carolan, Hannah [Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Olson, Robert [University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, BC Cancer Agency, Centre for the North, Prince George, British Columbia (Canada); Schellenberg, Devin [University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, BC Cancer Agency, Fraser Valley Centre, Surrey, British Columbia (Canada); Germain, François [University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, BC Cancer Agency, Sindi Ahluwalia Centre for the Southern Interior, Kelowna, British Columbia (Canada); Cheung, Arthur [University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, BC Cancer Agency, Fraser Valley Centre, Surrey, British Columbia (Canada); Peacock, Michael [Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); and others

    2016-02-01

    Purpose: Interest is growing in treating multiple brain metastases with radiosurgery. We report on the effectiveness and tolerability of volumetric radiosurgery (VRS). Methods and Materials: We enrolled patients with a ≥6-month estimated life expectancy and 1 to 10 brain metastases with a diameter of ≤3 cm at 5 cancer centers. Volumetric radiosurgery was delivered in 5 fractions with 98% target coverage, prescribed as 95% of 50 Gy (47.5 Gy in 5 fractions) to the metastases with no margin and 95% of 40 Gy (38 Gy in 5 fractions) to their 2-mm planning target volumes, concurrent with 20 Gy to the whole brain planning target volume. The treatment was delivered with daily image guidance using conventional linear accelerators and volumetric modulated arc therapy. A magnetic resonance imaging scan was obtained every 3 months. The primary endpoint was the 3-month objective response in the brain according to the Response Evaluation Criteria in Solid Tumors, version 1.1. The principal secondary endpoint was 1-year actuarial control of treated metastases. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. The present study is registered with (ClinicalTrials.gov) ( (clinicaltrials.gov) identifier (NCT01046123)). Results: From July 2010 to May 2013, 60 patients underwent VRS with 47.5 Gy in 5 fractions for 12 metastases in the thalamus and basal ganglia (deep metastases) and 207 non-deep metastases. The median follow-up period was 30.5 months, and the median survival was 10.1 months. For the 43 patients assessable at 3 months, the objective response in the brain was 56%. The treated metastases were controlled in 88% of patients at 1 year and 84% at 3 years. Overall survival did not differ for patients with 4 to 10 versus 1 to 3 metastases (hazard ratio 1.18, P=.6). The crude incidence of severe radionecrosis (grade 3-5) was 25% (3 of 12) per deep metastasis, 1.9% (4 of 219) per non-deep metastasis, and 10% (6 of 60

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

    Science.gov (United States)

    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.

  16. Stereotactic radiosurgery for treatment of brain metastases. A report of the DEGRO Working Group on Stereotactic Radiotherapy

    International Nuclear Information System (INIS)

    Kocher, Martin; Wittig, Andrea; Piroth, Marc Dieter; Treuer, Harald; Ruge, Maximilian; Seegenschmiedt, Heinrich; Grosu, Anca-Ligia; Guckenberger, Matthias

    2014-01-01

    This report from the Working Group on Stereotaktische Radiotherapie of the German Society of Radiation Oncology (Deutsche Gesellschaft fuer Radioonkologie, DEGRO) provides recommendations for the use of stereotactic radiosurgery (SRS) on patients with brain metastases. It considers existing international guidelines and details them where appropriate. The main recommendations are: Patients with solid tumors except germ cell tumors and small-cell lung cancer with a life expectancy of more than 3 months suffering from a single brain metastasis of less than 3 cm in diameter should be considered for SRS. Especially when metastases are not amenable to surgery, are located in the brain stem, and have no mass effect, SRS should be offered to the patient. For multiple (two to four) metastases - all less than 2.5 cm in diameter - in patients with a life expectancy of more than 3 months, SRS should be used rather than whole-brain radiotherapy (WBRT). Adjuvant WBRT after SRS for both single and multiple (two to four) metastases increases local control and reduces the frequency of distant brain metastases, but does not prolong survival when compared with SRS and salvage treatment. As WBRT carries the risk of inducing neurocognitive damage, it seems reasonable to withhold WBRT for as long as possible. A single (marginal) dose of 20 Gy is a reasonable choice that balances the effect on the treated lesion (local control, partial remission) against the risk of late side effects (radionecrosis). Higher doses (22-25 Gy) may be used for smaller ( [de

  17. Defining treatment for brain metastases patients: nihilism versus optimism.

    Science.gov (United States)

    Craighead, Peter S; Chan, Alexander

    2012-02-01

    Treatment of brain metastases patients has included whole brain radiotherapy (WBRT) for over 50 years, and there is much data showing this to be associated with short-term gains. The integration of resection and radiosurgery to these patients allows some better prognostic groups to experience long-term local control and improvement in quality of life. The recursive partitioning analysis of the Radiation Therapy Oncology Group (RTOG) has been used as a predictive model for over a decade to identify three classes of patients. Number of lesions has been used to define treatment for a good prognostic subgroup that is eligible for surgery or radiosurgery, but there are few prospective studies of poorer prognosis brain metastases patients to evaluate the influence of number of lesions on the prediction of outcome. We examined patient, treatment and outcome parameters of all brain metastases patients in a 5-year period so that we could measure outcome and evaluate various factors on survival. This was a population-based study of all brain metastases patients in Southern Alberta between 2000 and 2005. It used an Excel spreadsheet database and STATA 8 software to analyze outcomes. The study included 568 patients representing 4.4% of our radiotherapy population. Median age, performance status and distribution of primary disease sites were comparable with other large series. Overall survival for the whole group was 3.05 months. Independent factors predicting for improved overall survival included younger age, KPS <70, less than four lesions and the use of stereotactic radiosurgery. Presence of extracranial disease or persistence of primary disease did not adversely impact survival outcome. This series shows that the number of lesions is a strong predictor of outcome. Integration of this factor into a decision-making model allows for identification of not only good prognosis patients who will benefit from aggressive treatment but it also facilitates decision making for poorer

  18. 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...

  19. Classifying brain metastases by their primary site of origin using a radiomics approach based on texture analysis: a feasibility study.

    Science.gov (United States)

    Ortiz-Ramón, Rafael; Larroza, Andrés; Ruiz-España, Silvia; Arana, Estanislao; Moratal, David

    2018-05-14

    To examine the capability of MRI texture analysis to differentiate the primary site of origin of brain metastases following a radiomics approach. Sixty-seven untreated brain metastases (BM) were found in 3D T1-weighted MRI of 38 patients with cancer: 27 from lung cancer, 23 from melanoma and 17 from breast cancer. These lesions were segmented in 2D and 3D to compare the discriminative power of 2D and 3D texture features. The images were quantized using different number of gray-levels to test the influence of quantization. Forty-three rotation-invariant texture features were examined. Feature selection and random forest classification were implemented within a nested cross-validation structure. Classification was evaluated with the area under receiver operating characteristic curve (AUC) considering two strategies: multiclass and one-versus-one. In the multiclass approach, 3D texture features were more discriminative than 2D features. The best results were achieved for images quantized with 32 gray-levels (AUC = 0.873 ± 0.064) using the top four features provided by the feature selection method based on the p-value. In the one-versus-one approach, high accuracy was obtained when differentiating lung cancer BM from breast cancer BM (four features, AUC = 0.963 ± 0.054) and melanoma BM (eight features, AUC = 0.936 ± 0.070) using the optimal dataset (3D features, 32 gray-levels). Classification of breast cancer and melanoma BM was unsatisfactory (AUC = 0.607 ± 0.180). Volumetric MRI texture features can be useful to differentiate brain metastases from different primary cancers after quantizing the images with the proper number of gray-levels. • Texture analysis is a promising source of biomarkers for classifying brain neoplasms. • MRI texture features of brain metastases could help identifying the primary cancer. • Volumetric texture features are more discriminative than traditional 2D texture features.

  20. [Global brain metastases management strategy: a multidisciplinary-based approach].

    Science.gov (United States)

    Métellus, P; Tallet, A; Dhermain, F; Reyns, N; Carpentier, A; Spano, J-P; Azria, D; Noël, G; Barlési, F; Taillibert, S; Le Rhun, É

    2015-02-01

    Brain metastases management has evolved over the last fifteen years and may use varying strategies, including more or less aggressive treatments, sometimes combined, leading to an improvement in patient's survival and quality of life. The therapeutic decision is subject to a multidisciplinary analysis, taking into account established prognostic factors including patient's general condition, extracerebral disease status and clinical and radiological presentation of lesions. In this article, we propose a management strategy based on the state of current knowledge and available therapeutic resources. Copyright © 2015. Published by Elsevier SAS.

  1. 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.

  2. Management of Melanoma Brain Metastases in the Era of Targeted Therapy

    International Nuclear Information System (INIS)

    Shapiro, D. G.; Samlowski, W. E.; Samlowski, W. E.; Samlowski, W. E.; Samlowski, W. E.

    2011-01-01

    Disseminated metastatic disease, including brain metastases, is commonly encountered in malignant melanoma. The classical treatment approach for melanoma brain metastases has been neurosurgical resection followed by whole brain radiotherapy. Traditionally, if lesions were either too numerous or surgical intervention would cause substantial neurologic deficits, patients were either treated with whole brain radiotherapy or referred to hospice and supportive care. Chemotherapy has not proven effective in treating brain metastases. Improvements in surgery, radiosurgery, and new drug discoveries have provided a wider range of treatment options. Additionally, recently discovered mutations in the melanoma genome have led to the development of "targeted therapy."These vastly improved options are resulting in novel treatment paradigms for approaching melanoma brain metastases in patients with and without systemic metastatic disease. It is therefore likely that improved survival can currently be achieved in at least a subset of melanoma patients with brain metastases.

  3. Management of melanoma brain metastases in the era of targeted therapy.

    Science.gov (United States)

    Shapiro, Daniela Gonsalves; Samlowski, Wolfram E

    2011-01-01

    Disseminated metastatic disease, including brain metastases, is commonly encountered in malignant melanoma. The classical treatment approach for melanoma brain metastases has been neurosurgical resection followed by whole brain radiotherapy. Traditionally, if lesions were either too numerous or surgical intervention would cause substantial neurologic deficits, patients were either treated with whole brain radiotherapy or referred to hospice and supportive care. Chemotherapy has not proven effective in treating brain metastases. Improvements in surgery, radiosurgery, and new drug discoveries have provided a wider range of treatment options. Additionally, recently discovered mutations in the melanoma genome have led to the development of "targeted therapy." These vastly improved options are resulting in novel treatment paradigms for approaching melanoma brain metastases in patients with and without systemic metastatic disease. It is therefore likely that improved survival can currently be achieved in at least a subset of melanoma patients with brain metastases.

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

    Science.gov (United States)

    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.

  5. Molecular Concordance Between Primary Breast Cancer and Matched Metastases

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Thomassen, Mads

    2016-01-01

    Clinical management of breast cancer is increasingly personalized and based on molecular profiling. Often, primary tumors are used as proxies for systemic disease at the time of recurrence. However, recent studies have revealed substantial discordances between primary tumors and metastases, both....... The purpose of this review is to illuminate the extent of cancer genome evolution through disease progression and the degree of molecular concordance between primary breast cancers and matched metastases. We present an overview of the most prominent studies investigating the expression of endocrine receptors......, transcriptomics, and genome aberrations in primary tumors and metastases. In conclusion, biopsy of metastatic lesions at recurrence of breast cancer is encouraged to provide optimal treatment of the disease. Furthermore, molecular profiling of metastatic tissue provides invaluable mechanistic insight...

  6. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Choroidal Metastases as the Initial Presentation of Lung Cancer: A ...

    African Journals Online (AJOL)

    We report the case of a 49-year-old female patient who presented with ... nonsmall cell carcinoma of the right lung, which had multiple distant metastases. KEYWORDS: ... metastasis in lung cancer is very low, reported to be ... Kolkata, West Bengal, India. E-mail: .... awareness regarding this rare presentation of lung cancer.

  9. Prevention and Treatment of Bone Metastases in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ripamonti Carla

    2013-09-01

    Full Text Available In breast cancer patients, bone is the most common site of metastases. Medical therapies are the basic therapy to prevent distant metastases and recurrence and to cure them. Radiotherapy has a primary role in pain relief, recalcification and stabilization of the bone, as well as the reduction of the risk of complications (e.g., bone fractures, spinal cord compression. Bisphosphonates, as potent inhibitors of osteoclastic-mediated bone resorption are a well-established, standard-of-care treatment option to reduce the frequency, severity and time of onset of the skeletal related events in breast cancer patients with bone metastases. Moreover bisphosphonates prevent cancer treatment-induced bone loss. Recent data shows the anti-tumor activity of bisphosphonates, in particular, in postmenopausal women and in older premenopausal women with hormone-sensitive disease treated with ovarian suppression. Pain is the most frequent symptom reported in patients with bone metastases, and its prevention and treatment must be considered at any stage of the disease. The prevention and treatment of bone metastases in breast cancer must consider an integrated multidisciplinary approach.

  10. Whole brain helical Tomotherapy with integrated boost for brain metastases in patients with malignant melanoma–a randomized trial

    International Nuclear Information System (INIS)

    Hauswald, Henrik; Habl, Gregor; Krug, David; Kehle, Denise; Combs, Stephanie E; Bermejo, Justo Lorenzo; Debus, Jürgen; Sterzing, Florian

    2013-01-01

    Patients with malignant melanoma may develop brain metastases during the course of the disease, requiring radiotherapeutic treatment. In patients with 1–3 brain metastases, radiosurgery has been established as a treatment option besides surgery. For patients with 4 or more brain metastases, whole brain radiotherapy is considered the standard treatment. In certain patients with brain metastases, radiation treatment using whole brain helical Tomotherapy with integrated boost and hippocampal-sparing may improve prognosis of these patients. The present prospective, randomized two-armed trial aims to exploratory investigate the treatment response to conventional whole brain radiotherapy applying 30 Gy in 10 fractions versus whole brain helical Tomotherapy applying 30 Gy in 10 fractions with an integrated boost of 50 Gy to the brain metastases as well as hippocampal-sparing in patients with brain metastases from malignant melanoma. The main inclusion criteria include magnetic resonance imaging confirmed brain metastases from a histopathologically confirmed malignant melanoma in patients with a minimum age of 18 years. The main exclusion criteria include a previous radiotherapy of the brain and not having recovered from acute high-grade toxicities of prior therapies. The primary endpoint is treatment-related toxicity. Secondary endpoints include imaging response, local and loco-regional progression-free survival, overall survival and quality of life

  11. Multidose Stereotactic Radiosurgery (9 Gy × 3) of the Postoperative Resection Cavity for Treatment of Large Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Minniti, Giuseppe, E-mail: gminniti@ospedalesantandrea.it [Radiation Oncology Unit, Sant' Andrea Hospital, University “Sapienza,” Rome (Italy); Department of Neurological Sciences, Scientific Institute IRCCS Neuromed, Pozzilli (Italy); Esposito, Vincenzo [Department of Neurological Sciences, Scientific Institute IRCCS Neuromed, Pozzilli (Italy); Clarke, Enrico; Scaringi, Claudia [Radiation Oncology Unit, Sant' Andrea Hospital, University “Sapienza,” Rome (Italy); Lanzetta, Gaetano [Department of Neurological Sciences, Scientific Institute IRCCS Neuromed, Pozzilli (Italy); Salvati, Maurizio [Department of Neurological Sciences, Scientific Institute IRCCS Neuromed, Pozzilli (Italy); Neurosurgery Unit, Umberto I Hospital, University “Sapienza,” Rome (Italy); Raco, Antonino [Neurosurgery Unit, Sant' Andrea Hospital, University “Sapienza,” Rome (Italy); Bozzao, Alessandro [Neuroradiology Unit, Sant' Andrea Hospital, University “Sapienza,” Rome (Italy); Maurizi Enrici, Riccardo [Radiation Oncology Unit, Sant' Andrea Hospital, University “Sapienza,” Rome (Italy)

    2013-07-15

    Purpose: To evaluate the clinical outcomes with linear accelerator-based multidose stereotactic radiosurgery (SRS) to large postoperative resection cavities in patients with large brain metastases. Methods and Materials: Between March 2005 to May 2012, 101 patients with a single brain metastasis were treated with surgery and multidose SRS (9 Gy × 3) for large resection cavities (>3 cm). The target volume was the resection cavity with the inclusion of a 2-mm margin. The median cavity volume was 17.5 cm{sup 3} (range, 12.6-35.7 cm{sup 3}). The primary endpoint was local control. Secondary endpoints were survival and distant failure rates, cause of death, performance measurements, and toxicity of treatment. Results: With a median follow-up of 16 months (range, 6-44 months), the 1-year and 2-year actuarial survival rates were 69% and 34%, respectively. The 1-year and 2-year local control rates were 93% and 84%, with respective incidences of new distant brain metastases of 50% and 66%. Local control was similar for radiosensitive (non-small cell lung cancer and breast cancer) and radioresistant (melanoma and renal cell cancer) brain metastases. On multivariate Cox analysis stable extracranial disease, breast cancer histology, and Karnofsky performance status >70 were associated with significant survival benefit. Brain radionecrosis occurred in 9 patients (9%), being symptomatic in 5 patients (5%). Conclusions: Adjuvant multidose SRS to resection cavity represents an effective treatment option that achieves excellent local control and defers the use of whole-brain radiation therapy in selected patients with large brain metastases.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Primary brain tumours, meningiomas and brain metastases in pregnancy

    DEFF Research Database (Denmark)

    Verheecke, Magali; Halaska, Michael J; Lok, Christianne A

    2014-01-01

    to obtain better insight into outcome and possibilities of treatment in pregnancy. METHODS: We collected all intracranial tumours (primary brain tumour, cerebral metastasis, or meningioma) diagnosed during pregnancy, registered prospectively and retrospectively by international collaboration since 1973......, respectively. Eight patients (30%) underwent brain surgery, seven patients (26%) had radiotherapy and in three patients (11%) chemotherapy was administered during gestation. Two patients died during pregnancy and four pregnancies were terminated. In 16 (59%) patients elective caesarean section was performed...... were reassuring. CONCLUSION: Adherence to standard protocol for the treatment of brain tumours during pregnancy appears to allow a term delivery and a higher probability of a vaginal delivery....

  14. Response assessment criteria for brain metastases : proposal from the RANO group

    NARCIS (Netherlands)

    Lin, Nancy U.; Lee, Eudocia Q.; Aoyama, Hidefumi; Barani, Igor J.; Barboriak, Daniel P.; Baumert, Brigitta G.; Bendszus, Martin; Brown, Paul D.; Camidge, D. Ross; Chang, Susan M.; Dancey, Janet; de Vries, Elisabeth G. E.; Gaspar, Laurie E.; Harris, Gordon J.; Hodi, F. Stephen; Kalkanis, Steven N.; Linskey, Mark E.; Macdonald, David R.; Margolin, Kim; Mehta, Minesh P.; Schiff, David; Soffietti, Riccardo; Suh, John H.; van den Bent, Martin J.; Vogelbaum, Michael A.; Wen, Patrick Y.

    CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation

  15. Adverse radiation effect after stereotactic radiosurgery for brain metastases : incidence, time course, and risk factors

    NARCIS (Netherlands)

    Sneed, Penny K.; Mendez, Joe; Vemer-van den Hoek, Johanna; Seymour, Zachary A.; Ma, Lijun; Molinaro, Annette M.; Fogh, Shannon E.; Nakamura, Jean L.; McDermott, Michael W.

    OBJECT The authors sought to determine the incidence, time course, and risk factors for overall adverse radiation effect (ARE) and symptomatic ARE after stereotactic radiosurgery (SRS) for brain metastases. METHODS All cases of brain metastases treated from 1998 through 2009 with Gamma Knife SRS at

  16. Stereotactic radiosurgery for the treatment of brain metastases; results from a single institution experience.

    LENUS (Irish Health Repository)

    Burke, D

    2013-09-01

    Stereotactic radiosurgery is frequently used for the treatment of brain metastases. This study provides a retrospective evaluation of patients with secondary lesions of the brain treated with stereotactic radiosurgery (SRS) at our institution.

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

    Directory of Open Access Journals (Sweden)

    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

  18. External Validity of a Risk Stratification Score Predicting Early Distant Brain Failure and Salvage Whole Brain Radiation Therapy After Stereotactic Radiosurgery for Brain Metastases.

    Science.gov (United States)

    Press, Robert H; Boselli, Danielle M; Symanowski, James T; Lankford, Scott P; McCammon, Robert J; Moeller, Benjamin J; Heinzerling, John H; Fasola, Carolina E; Burri, Stuart H; Patel, Kirtesh R; Asher, Anthony L; Sumrall, Ashley L; Curran, Walter J; Shu, Hui-Kuo G; Crocker, Ian R; Prabhu, Roshan S

    2017-07-01

    A scoring system using pretreatment factors was recently published for predicting the risk of early (≤6 months) distant brain failure (DBF) and salvage whole brain radiation therapy (WBRT) after stereotactic radiosurgery (SRS) alone. Four risk factors were identified: (1) lack of prior WBRT; (2) melanoma or breast histologic features; (3) multiple brain metastases; and (4) total volume of brain metastases external patient population. We reviewed the records of 247 patients with 388 brain metastases treated with SRS between 2010 at 2013 at Levine Cancer Institute. The Press (Emory) risk score was calculated and applied to the validation cohort population, and subsequent risk groups were analyzed using cumulative incidence. The low-risk (LR) group had a significantly lower risk of early DBF than did the high-risk (HR) group (22.6% vs 44%, P=.004), but there was no difference between the HR and intermediate-risk (IR) groups (41.2% vs 44%, P=.79). Total lesion volume externally valid, but the model was able to stratify between 2 levels (LR and not-LR [combined IR and HR]) for early (≤6 months) DBF. These results reinforce the importance of validating predictive models in independent cohorts. Further refinement of this scoring system with molecular information and in additional contemporary patient populations is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Brain-Only Metastases Seen on FDG PET as First Relapse of Papillary Thyroid Carcinoma Two Years Post-Thyroidectomy.

    Science.gov (United States)

    Naddaf, Sleiman Y; Syed, Ghulam Mustafa Shah; Hadb, Abdulrahman; Al-Thaqfi, Saif

    2016-09-01

    We report a case of a 60-year-old man diagnosed with papillary thyroid cancer who had a relapse seen only in the brain at FDG PET on standard images. Total thyroidectomy was performed in July 2013 after initial diagnosis. Patient received I ablation in December 2013, followed by external beam radiotherapy to the neck. In September 2015, the patient presented with neurological symptoms. Brain MRI showed multiple brain metastases later confirmed on histopathology. An FDG PET/CT scan was performed to evaluate the whole body in November 2015. Multiple hypermetabolic lesions were identified in the brain with no other lesion up to mid thighs.

  20. Mechanoresponsive stem cells to target cancer metastases through biophysical cues.

    Science.gov (United States)

    Liu, Linan; Zhang, Shirley X; Liao, Wenbin; Farhoodi, Henry P; Wong, Chi W; Chen, Claire C; Ségaliny, Aude I; Chacko, Jenu V; Nguyen, Lily P; Lu, Mengrou; Polovin, George; Pone, Egest J; Downing, Timothy L; Lawson, Devon A; Digman, Michelle A; Zhao, Weian

    2017-07-26

    Despite decades of effort, little progress has been made to improve the treatment of cancer metastases. To leverage the central role of the mechanoenvironment in cancer metastasis, we present a mechanoresponsive cell system (MRCS) to selectively identify and treat cancer metastases by targeting the specific biophysical cues in the tumor niche in vivo. Our MRCS uses mechanosensitive promoter-driven mesenchymal stem cell (MSC)-based vectors, which selectively home to and target cancer metastases in response to specific mechanical cues to deliver therapeutics to effectively kill cancer cells, as demonstrated in a metastatic breast cancer mouse model. Our data suggest a strong correlation between collagen cross-linking and increased tissue stiffness at the metastatic sites, where our MRCS is specifically activated by the specific cancer-associated mechano-cues. MRCS has markedly reduced deleterious effects compared to MSCs constitutively expressing therapeutics. MRCS indicates that biophysical cues, specifically matrix stiffness, are appealing targets for cancer treatment due to their long persistence in the body (measured in years), making them refractory to the development of resistance to treatment. Our MRCS can serve as a platform for future diagnostics and therapies targeting aberrant tissue stiffness in conditions such as cancer and fibrotic diseases, and it should help to elucidate mechanobiology and reveal what cells "feel" in the microenvironment in vivo. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  1. CSF-ctDNA SMSEQ Analysis to Tailor the Treatment of a Patient with Brain Metastases: A Case Report

    Directory of Open Access Journals (Sweden)

    Wen-Tsung  Huang

    2018-02-01

    Full Text Available Brain metastases are the most common neurological complications of adult cancers, accounting for more than half of brain tumors. The incidence of brain metastases may be increasing due to improved detection of small lesions by advanced imaging technologies. Given the fast evolution of targeted and immunotherapy regimens, it is essential to serially assess brain malignancies during the disease course for disease monitoring and tailoring of the therapeutic management. For such serial and repetitive assessment, cerebrospinal fluid (CSF could be the biological fluid of choice to supplement cytology examination for the presence or absence of CNS malignancy, as well as provide extensive information on tumor mutational profile for personalization of treatment. The case described here emphasizes the importance of CSF-ctDNA analysis with the CellMax SMSEQ technology that led to treatment adjustment resulting in clinical remission of the patient.

  2. Isolated brain metastases of osteosarcoma in a patient presenting with a patent foramen ovale

    International Nuclear Information System (INIS)

    Menassa, L.; Haddad, S.; Aoun, N.; Slaba, S.; Atallah, N.

    1997-01-01

    We report the case of a patient in whom brain MR imaging was requested for initial symptoms of intracranial hypertension. The presence of multiple intracranial hemorrhagic lesions suggested brain metastases. Body screening showed periosteal osteosarcoma of the left fibula with no lung metastases, but with a patent foramen ovale which probably allowed neoplastic cells to reach the brain without being filtered through the lungs. The conclusion of this study was that a left-right cardiac communication is to be considered in cases of isolated brain metastases from osteosarcoma. (orig.). With 3 figs

  3. Stereotactic radiosurgery for newly diagnosed brain metastases. Comparison of three dose levels

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); Hornung, Dagmar [University Medical Center Hamburg-Eppendorf, Department of Radiation Oncology, Hamburg (Germany); Blanck, Oliver [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); CyberKnife Center Northern Germany, Guestrow (Germany); Martens, Kristina [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); University of Luebeck, Center for Integrative Psychiatry, Luebeck (Germany); Khoa, Mai Trong [Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam); Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Trang, Ngo Thuy [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Hueppe, Michael [University of Luebeck, Department of Anesthesiology, Luebeck (Germany); Terheyden, Patrick [University of Luebeck, Department of Dermatology, Luebeck (Germany); Gliemroth, Jan [University of Luebeck, Department of Neurosurgery, Luebeck (Germany); Schild, Steven E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale (United States)

    2014-09-15

    Three doses were compared for local control of irradiated metastases, freedom from new brain metastases, and survival in patients receiving stereotactic radiosurgery (SRS) alone for one to three newly diagnosed brain metastases. In all, 134 patients were assigned to three groups according to the SRS dose given to the margins of the lesions: 13-16 Gy (n = 33), 18 Gy (n = 18), and 20 Gy (n = 83). Additional potential prognostic factors were evaluated: age (≤ 60 vs. > 60 years), gender, Karnofsky Performance Scale score (70-80 vs. 90-100), tumor type (non-small-cell lung cancer vs. melanoma vs. others), number of brain metastases (1 vs. 2-3), lesion size (< 15 vs. ≥ 15 mm), extracranial metastases (no vs. yes), RPA class (1 vs. 2), and interval of cancer diagnosis to SRS (≤ 24 vs. > 24 months). For 13-16 Gy, 18 Gy, and 20 Gy, the 1-year local control rates were 31, 65, and 79 %, respectively (p < 0.001). The SRS dose maintained significance on multivariate analysis (risk ratio: 2.25; 95 % confidence interval: 1.56-3.29; p < 0.001). On intergroup comparisons of local control, 20 Gy was superior to 13-16 Gy (p < 0.001) but not to 18 Gy (p = 0.12); 18 Gy showed a strong trend toward better local control when compared with 13-16 Gy (p = 0.059). Freedom from new brain metastases (p = 0.57) and survival (p = 0.15) were not associated with SRS dose in the univariate analysis. SRS doses of 18 Gy and 20 Gy resulted in better local control than 13-16 Gy. However, 20 Gy and 18 Gy must be compared again in a larger cohort of patients. Freedom from new brain metastases and survival were not associated with SRS dose. (orig.) [German] Drei Dosislevel bei der alleinigen stereotaktischen Radiochirurgie (SRS) von 1 bis 3 neu diagnostizierten Hirnmetastasen wurden hinsichtlich lokaler Kontrolle der bestrahlten Metastasen, Nichtauftreten neuer Hirnmetastasen und Gesamtueberleben verglichen. Nach der am Rand der Metastasen applizierten SRS-Dosis wurden 134 Patienten den Gruppen 13

  4. Intraoperative ultrasonography for presumed brain metastases: a case series study

    Directory of Open Access Journals (Sweden)

    Helder Picarelli

    2012-10-01

    Full Text Available Brain metastases (BM are one of the most common intracranial tumors and surgical treatment can improve both the functional outcomes and patient survival, particularly when systemic disease is controlled. Image-guided BM resection using intraoperative exams, such as intraoperative ultrasound (IOUS, can lead to better surgical results. METHODS: To evaluate the use of IOUS for BM resection, 20 consecutives patients were operated using IOUS to locate tumors, identify their anatomical relationships and surgical cavity after resection. Technical difficulties, complications, recurrence and survival rates were noted. RESULTS: IOUS proved effective for locating, determining borders and defining the anatomical relationships of BM, as well as to identify incomplete tumor resection. No complications related to IOUS were seen. CONCLUSION: IOUS is a practical supporting method for the resection of BM, but further studies comparing this method with other intraoperative exams are needed to evaluate its actual contribution and reliability.

  5. Lung cancer revealed by multiple metastases of the scalp | Fetohi ...

    African Journals Online (AJOL)

    Skin metastases of lung cancer are rare. They are symptoms of progressive disease and usually a sign of a poor prognosis. We report a case of 69-years-old man with no significant medical history, never smoker, which consulted a dermatologist for scalp nodules that appeared for more than 16 months in the scalp and ...

  6. B metastases in breast cancer. Clinical, diagnostic and therapeutic aspects

    International Nuclear Information System (INIS)

    Ferrigno, R.; Petitto, J.V.

    1989-01-01

    Osseous metastases are the most frequent sites of dissemination in breast cancer and diminish the quality of patients life, being one of the most serious problems of the disease. The authors discuss the clinical, diagnosis and therapeutic aspects, based on their own experience and data from the literature. (author)

  7. Osteopoikilosis: A Sign Mimicking Skeletal Metastases in a Cancer Patient

    Directory of Open Access Journals (Sweden)

    Hamid Nasrolahi

    2011-01-01

    Full Text Available Osteopoikilosis is a rare benign osteosclerotic bone disorder that may be misdiagnosed as skeletal metastases. Here we describe a case of coincidental breast cancer and osteopoikilosis mimicking skeletal metastases. A 41-year-old woman underwent right modified radical mastectomy in April 2007. Twenty-eight months after initial treatment,the patient complained of bilateral knee and foot pain. Plain X-rays of the feet and knees showed multiple well-defined osteosclerotic lesions. According to the radiographic appearance, the most likely differential diagnoses included skeletal metastases from breast cancer and osteopoikilosis. A whole-body bone scintigraphy showed no increase in uptake by the sclerotic lesions, and serum lactic dehydrogenase, carcinoembryonic antigen, alkaline phosphatase and cancer antigen 15-3 were not elevated. We therefore diagnosed the patient’s skeletal lesions as osteopoikilosis. This case and ourliterature review suggest that the radiographic appearance of osteopoikilosis may mimic or mask skeletal metastases, potentially leading to misdiagnosis in patients with cancer.

  8. Osteoblast-Prostate Cancer Cell Interaction in Prostate Cancer Bone Metastases

    National Research Council Canada - National Science Library

    Navone, Nora

    2001-01-01

    .... This suggests that prostate cancer cells interact with cells from the osteoblastic lineage. To understand the molecular bases of prostatic bone metastases, we established two prostate cancer cell lines, MDA PCa 2a and MDA PCa 2b (1...

  9. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment

    Directory of Open Access Journals (Sweden)

    Tallet Agnes V

    2012-05-01

    Full Text Available Abstract Whole brain radiation therapy (WBRT is an effective treatment in brain metastases and, when combined with local treatments such as surgery and stereotactic radiosurgery, gives the best brain control. Nonetheless, WBRT is often omitted after local treatment due to its potential late neurocognitive effects. Publications on radiation-induced neurotoxicity have used different assessment methods, time to assessment, and definition of impairment, thus making it difficult to accurately assess the rate and magnitude of the neurocognitive decline that can be expected. In this context, and to help therapeutic decision making, we have conducted this literature review, with the aim of providing an average incidence, magnitude and time to occurrence of radio-induced neurocognitive decline. We reviewed all English language published articles on neurocognitive effects of WBRT for newly diagnosed brain metastases or with a preventive goal in adult patients, with any methodology (MMSE, battery of neurcognitive tests with which baseline status was provided. We concluded that neurocognitive decline is predominant at 4 months, strongly dependant on brain metastases control, partially solved at later time, graded 1 on a SOMA-LENT scale (only 8% of grade 2 and more, insufficiently assessed in long-term survivors, thus justifying all efforts to reduce it through irradiation modulation.

  10. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment

    International Nuclear Information System (INIS)

    Tallet, Agnes V; Azria, David; Barlesi, Fabrice; Spano, Jean-Philippe; Carpentier, Antoine F; Gonçalves, Antony; Metellus, Philippe

    2012-01-01

    Whole brain radiation therapy (WBRT) is an effective treatment in brain metastases and, when combined with local treatments such as surgery and stereotactic radiosurgery, gives the best brain control. Nonetheless, WBRT is often omitted after local treatment due to its potential late neurocognitive effects. Publications on radiation-induced neurotoxicity have used different assessment methods, time to assessment, and definition of impairment, thus making it difficult to accurately assess the rate and magnitude of the neurocognitive decline that can be expected. In this context, and to help therapeutic decision making, we have conducted this literature review, with the aim of providing an average incidence, magnitude and time to occurrence of radio-induced neurocognitive decline. We reviewed all English language published articles on neurocognitive effects of WBRT for newly diagnosed brain metastases or with a preventive goal in adult patients, with any methodology (MMSE, battery of neurcognitive tests) with which baseline status was provided. We concluded that neurocognitive decline is predominant at 4 months, strongly dependant on brain metastases control, partially solved at later time, graded 1 on a SOMA-LENT scale (only 8% of grade 2 and more), insufficiently assessed in long-term survivors, thus justifying all efforts to reduce it through irradiation modulation

  11. The role of whole brain radiotherapy and stereotactic radiosurgery on brain metastases from renal cell carcinoma

    International Nuclear Information System (INIS)

    Goyal, Lav K.; Suh, John H.; Reddy, Chandana A.; Barnett, Gene H.

    2000-01-01

    Purpose: We reviewed our experience with patients who have undergone stereotactic radiosurgery (SRS) for brain metastases secondary to renal cell carcinoma (RCC). Analysis was performed to determine the survival, local control, distant brain failure (DBF), and then to define which tumors may not require upfront whole-brain radiotherapy (WBRT). Methods and Materials: Twenty-nine patients with 66 tumors underwent SRS from 1991 to 1998. Median follow-up from time of brain metastases diagnoses relative to each tumor was 12.5 months and 6.8 months from the time of SRS. Median SRS dose was 1,800 cGy to the 60% isodose line. Three patients had undergone SRS for previously treated tumors. Results: Median survival time from diagnosis was 10.0 months. Overall survival was not affected by age, addition of WBRT, number of lesions, tumor volume, or the presence of systemic disease. Of the 23 patients with follow-up neuroimaging, 4 of 47 (9%) tumors recurred. The addition of WBRT did not improve local control. Of the 13 patients who presented with a single lesion, 3 went on to develop DBF (23%), while 6 of the 10 patients who presented with multiple metastases developed DBF (60%). Conclusion: Patients with brain metastases secondary to RCC treated by SRS alone have excellent local control. The decision of whether or not to add WBRT to SRS should depend on whether the patient has a high likelihood of developing DBF. Our study suggests that patients who present with multiple brain lesions may be more likely to benefit from the addition of WBRT because they appear to be more than twice as likely to develop DBF as compared to patients with a single lesion

  12. Intraoperative ultrasonography in detection of hepatic metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael; Kronborg, Ole; Fenger, Claus

    1995-01-01

    PURPOSE: This study was designed to compare diagnostic accuracies of measuring liver enzymes, preoperative ultrasonography, surgical examination, and intraoperative ultrasonography for detection of liver metastases from colorectal cancer. METHODS: Blind, prospective comparisons of diagnostic...... examinations mentioned above were performed in 295 consecutive patients with colorectal cancer. An experienced ultrasonologist performed the preoperative examinations, and results were unknown to the other experienced ultrasonologist who performed the intraoperative examinations. The latter, also was unaware...

  13. 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.

  14. Cognitive dysfunction in patients with brain metastases: influences on caregiver resilience and coping.

    Science.gov (United States)

    Saria, Marlon Garzo; Courchesne, Natasia; Evangelista, Lorraine; Carter, Joshua; MacManus, Daniel A; Gorman, Mary Kay; Nyamathi, Adeline M; Phillips, Linda R; Piccioni, David; Kesari, Santosh; Maliski, Sally

    2017-04-01

    Neurologic deficits that may be manifested as cognitive impairment contribute to the challenges faced by caregivers of patients with brain metastases. To better address their needs, we examined how caregivers respond to these challenges and explore the relationship between the patient's cognitive impairment and caregiver resilience and coping. We conducted a descriptive, cross-sectional study using self-reported data from 56 caregivers of patients with brain metastases. Study participants from a comprehensive cancer center were asked to complete a series of instruments that measured their perception of the patient's cognitive dysfunction (revised memory and behavior problems checklist, RMBC), their own personal resilience (Resilience Scale, RS), and their utilization of a broad range of coping responses (COPE inventory and Emotional-Approach Coping scale). Caregivers reported that memory-related problems occurred more frequently in the patients they cared for compared to depression and disruptive behavior (mean scores 3.52 vs 2.34 vs. 1.32, respectively). Coping strategies most frequently used by caregivers were acceptance (3.28), planning (3.08), and positive reinterpretation and growth (2.95). Most caregivers scored moderate to high on the RS (77%). The coping strategy acceptance correlated significantly with the memory and disruptive behavior subscales of the RMBC. Given the protective effect of problem-focused coping and the high rate of caregivers utilizing less effective coping strategies in instances of worsening cognitive dysfunction, healthcare professionals need to systematically assess the coping strategies of caregivers and deliver a more personalized approach to enhance effective coping among caregivers of patients with brain metastases.

  15. Accelerated regression of brain metastases in patients receiving whole brain radiation and the topoisomerase II inhibitor, lucanthone

    International Nuclear Information System (INIS)

    Rowe, John D. del; Bello, Jacqueline; Mitnick, Robin; Sood, Brij; Filippi, Christopher; Moran, Justin Ph.D.; Freeman, Katherine; Mendez, Frances; Bases, Robert

    1999-01-01

    Purpose: To determine if lucanthone crossed the blood-brain barrier in experimental animals; and to determine accelerated tumor regression of human brain metastases treated jointly with lucanthone and whole brain radiation. Methods and Materials: The organ distribution of 3 H lucanthone in mice and 125 I lucanthone in rats was determined to learn if lucanthone crossed the blood-brain barrier. Size determinations were made of patients' brain metastases from magnetic resonance images or by computed tomography before and after treatment with 30 Gy whole brain radiation alone or with lucanthone. Results: The time course of lucanthone's distribution in brain was identical to that in muscle and heart after intraperitoneal or intravenous administration in experimental animals. Lucanthone, therefore, readily crossed the blood-brain barrier in experimental animals. Conclusion: Compared with radiation alone, the tumor regression in patients with brain metastases treated with lucanthone and radiation was accelerated, approaching significance using a permutation test at p = 0.0536

  16. SURGICAL TREATMENT FOR KIDNEY CANCER METASTASES TO THE LONG TUBULAR BONES

    Directory of Open Access Journals (Sweden)

    S. V. Kostritsky

    2014-07-01

    Full Text Available The data of 35 kidney cancer patients with metastases in long bones, who had been operated, were retrospectively analyzed. The role of surgery in patients with long bones metastases of kidney cancer was assessed and application of surgical treatment was ascertained to yield satisfactory results in improving the quality of life and duration of life in patients with solitary bone metastases.

  17. SURGICAL TREATMENT FOR KIDNEY CANCER METASTASES TO THE LONG TUBULAR BONES

    Directory of Open Access Journals (Sweden)

    S. V. Kostritsky

    2013-01-01

    Full Text Available The data of 35 kidney cancer patients with metastases in long bones, who had been operated, were retrospectively analyzed. The role of surgery in patients with long bones metastases of kidney cancer was assessed and application of surgical treatment was ascertained to yield satisfactory results in improving the quality of life and duration of life in patients with solitary bone metastases.

  18. Comparison of survival of patients with metastases from known versus unknown primaries: survival in metastatic cancer

    Directory of Open Access Journals (Sweden)

    Riihimäki Matias

    2013-01-01

    Full Text Available Abstract Background Cancer of unknown primary site (CUP is considered an aggressive metastatic disease but whether the prognosis differs from metastatic cancers of known primary site is not known. Such data may give insight into the biology of CUP and the metastatic process in general. Methods 6,745 cancer patients, with primary metastatic cancer at diagnosis, were identified from the Swedish Cancer Registry, and were compared with 2,881 patients with CUP. Patients were diagnosed and died between 2002 and 2008. The influence of the primary site, known or unknown, on survival in patients with metastases at specific locations was investigated. Hazard ratios (HRs of death were estimated for several sites of metastasis, where patients with known primary sites were compared with CUP patients. Results Overall, patients with metastatic cancers with known primary sites had decreased hazards of death compared to CUP patients (HR = 0.69 [95% CI = 0.66–0.72]. The exceptions were cancer of the pancreas (1.71 [1.54–1.90], liver (1.58 [1.36–1.85], and stomach (1.16 [1.02–1.31]. For individual metastatic sites, patients with liver or bone metastases of known origin had better survival than those with CUP of the liver and bone. Patients with liver metastases of pancreatic origin had an increased risk of death compared with patients with CUP of the liver (1.25 [1.06–1.46]. The median survival time of CUP patients was three months. Conclusions Patients with CUP have poorer survival than patients with known primaries, except those with brain and respiratory system metastases. Of CUP sites, liver metastases had the worst prognosis. Survival in CUP was comparable to that in metastatic lung cancer. The aggressive behavior of CUP may be due to initial immunosuppression and immunoediting which may allow accumulation of mutations. Upon escape from the suppressed state an unstoppable tumor spread ensues. These novel data on the epidemiology of the

  19. Analysis of fractional anisotropy facilitates differentiation of glioblastoma and brain metastases in a clinical setting

    Energy Technology Data Exchange (ETDEWEB)

    Bette, Stefanie, E-mail: stefanie.bette@tum.de [Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Huber, Thomas; Wiestler, Benedikt; Boeckh-Behrens, Tobias [Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [Department of Neurosurgery, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Zimmer, Claus; Kirschke, Jan S. [Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich (Germany)

    2016-12-15

    Purpose: Differentiating glioblastoma from brain metastases is important for therapy planning. Diffusion tensor imaging (DTI) was described as a promising tool, however with conflicting results. Aim: of this study was to analyze the clinical utility of DTI for the differentiation of brain metastases and glioblastoma. Methods: 294 patients (165 glioblastoma, 129 brain metastases) with preoperative DTI were included in this retrospective study. Fractional anisotropy (FA) was measured via regions of interest (ROIs) in the contrast-enhancing tumor, the necrosis and the FLAIR-hyperintense non-enhancing peritumoral region (NEPTR). Two neuroradiologists classified patient cases as glioblastoma or brain metastases without and with knowledge of FA values. Results: Glioblastoma showed significantly higher FA{sub contrast} (median glioblastoma = 0.33, metastases = 0.23; P < 0.001) whereas no significant difference was observed for FA{sub NEPTR} (0.21 vs. 0.22; P = 0.28) and for FA{sub necrosis} (0.17 vs. 0.18, P = 0.37). FA improved diagnostic accuracy of the neuroradiologists significantly from an AUC of 0.84/0.85 (Reader1/Reader2) to 0.89/0.92. Conclusions: Glioblastoma show significantly higher FA values in the contrast enhancing tumor part than brain metastases. Implementation of a ROI-based measurement of FA values and FA color maps in clinical routine helps to differentiate between glioblastoma and brain metastases.

  20. Treatment of different cases o esophageal cancer metastases

    International Nuclear Information System (INIS)

    Pirogov, A.I.; Ryndin, V.D.

    1983-01-01

    Treatment of esophagus cancer taking into account frequency of metastatic spread in lymph nodes of different esophagus sections is presented. In the case of metastases in retroperitoneal lymph nodes esophagus resection is useless and radiation therapy is of palliation character. After removal of metastases in paracardial lymph nodes and nodes of the lesser omentum the patients should be considered as a group for provesory radical surgery, radiation and combined treatment for subsequent evaluation of the treatment expediency as more data are accumulated. In cases of middle mediastinum cancer of the lower third of esophagus all lymph nodes along esophagus below bifurcation of the trachea should be subjected to surgical (radiation) treatment. In the case of median third of esophagus cancer - the nodes along the entire thoracic part of the esophagus. For radiation therapy of the upper third of the esophagus irradiation fields should comprise lymph nodes along the esophagus above bifurcation of the trachea and cervicosubclavicular lymph nodes

  1. Clinicopathological features and outcome in advanced colorectal cancer patients with synchronous vs metachronous metastases

    NARCIS (Netherlands)

    Mekenkamp, L. J. M.; Koopman, M.; Teerenstra, S.; van Krieken, J. H. J. M.; Mol, L.; Nagtegaal, I. D.; Punt, C. J. A.

    2010-01-01

    Synchronous metastases of colorectal cancer (CRC) are considered to be of worse prognostic value compared with metachronous metastases, but only few and conflicting data have been reported on this issue. We retrospectively investigated patient demographics, primary tumour characteristics and overall

  2. Sentinel Lymph Node Occult Metastases Have Minimal Survival Effect in Some Breast Cancer Patients

    Science.gov (United States)

    Detailed examination of sentinel lymph node tissue from breast cancer patients revealed previously unidentified metastases in about 16% of the samples, but the difference in 5-year survival between patients with and without these metastases was very small

  3. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    Science.gov (United States)

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  4. AR Expression in Breast Cancer CTCs Associates with Bone Metastases.

    Science.gov (United States)

    Aceto, Nicola; Bardia, Aditya; Wittner, Ben S; Donaldson, Maria C; O'Keefe, Ryan; Engstrom, Amanda; Bersani, Francesca; Zheng, Yu; Comaills, Valentine; Niederhoffer, Kira; Zhu, Huili; Mackenzie, Olivia; Shioda, Toshi; Sgroi, Dennis; Kapur, Ravi; Ting, David T; Moy, Beverly; Ramaswamy, Sridhar; Toner, Mehmet; Haber, Daniel A; Maheswaran, Shyamala

    2018-04-01

    Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing was performed of circulating tumor cells (CTC) isolated from blood samples of women with metastatic estrogen receptor (ER) + breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7. AR expression within CTCs is correlated with the duration of treatment with aromatase inhibitors, suggesting that it contributes to acquired resistance to endocrine therapy. In an established breast cancer xenograft model, a bone-tropic derivative displays increased AR expression, whose genetic or pharmacologic suppression reduces metastases to bone but not to lungs. Together, these observations identify AR signaling in CTCs from women with bone-predominant ER + breast cancer, and provide a rationale for testing androgen inhibitors in this subset of patients. Implications: This study highlights a role for the AR in breast cancer bone metastasis, and suggests that therapeutic targeting of the AR may benefit patients with metastatic breast cancer. Mol Cancer Res; 16(4); 720-7. ©2018 AACR . ©2018 American Association for Cancer Research.

  5. [Isolated splenic metastases from cervical cancer: a rare entity].

    Science.gov (United States)

    Villalón-López, José Sebastián; Souto-del Bosque, Rosalía; Montañez-Lugo, Juan Ignacio; Chávez-González, Bruno

    2014-01-01

    Splenic metastases from solid tumors are a rare event with an incidence of only 2.9% to 9%. Splenic metastases from cervical cancer are a rare entity. Only a few cases have been reported of isolated spleen metastases from cervical cancer. We present the case of a 76-year-old woman with moderately differentiated endocervical adenocarcinoma stromal and endocervical invasion. Clinical stage was Ib1 and Ca-125 values of 150 U. She was managed with hysterectomy and pelvic lymphadenectomy. She received pelvic radiotherapy (45 Gy) followed 24 Gy of brachytherapy. Two years later she presented with abdominal pain. Abdominal computed tomography showed two splenic parenchymal lesions without disease in the remainder of the abdominal cavity and chest with a Ca-125 of 2,733 U. The patient is submitted to splenectomy. Histopathology demonstrates splenic metastases of well-differentiated adenocarcinoma from the endocervix. Immunohistochemical stain showed positivity from carcinoembryonic antigen; estrogen and progesterone receptors are negative. Ca-125 level 8 weeks after surgery was 16 U/ml. The patient received six cycles of adjuvant chemotherapy with paclitaxel and cisplatin. At 12 months follow-up the patient is alive and without evidence of tumor activity. The spleen is an uncommon site of metastasis. Splenectomy is considered the appropriate treatment in order to avoid complications such as splenic rupture and splenic vein thrombosis as well as to improve pain control from splenomegaly. Twelve months after surgery our patient is alive and without evidence of tumor activity.

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

    DEFF Research Database (Denmark)

    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

  7. A case of brain and leptomeningeal metastases from urothelial carcinoma of the bladder.

    Science.gov (United States)

    Erhamamcı, S; Reyhan, M; Altinkaya, N

    2014-01-01

    Brain metastases are unusual from urethelial carcinoma of bladder and particularly the occurrence of leptomeningeal metastases is extremely rare, with few cases described in the literature. We present a case of a 45-year-old man with a rare brain metastases as the first metastatic manifestation secondary to urethelial carcinoma of bladder followed by leptomeningeal metastases without any other organ involvement. Eleven months after the diagnosis of high-grade urethelial carcinoma of bladder (T2N0M0), the patient was detected having brain metastases by MRI. FDG PET/CT images for the metastatic evaluation showed no abnormal FDG uptake elsewhere in the body except the brain. Histopathology examination from brain lesion demonstrated the cerebral lesion to be a metastatic urothelial carcinoma. Two months later, the patient was diagnosed to have leptomeningeal metastases by MRI. Our patient's condition gradually worsened, and he died 3 months after the diagnosis of leptomeningeal metastases. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  8. 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 

  9. Combining stereotactic radiosurgery and systemic therapy for brain metastases: a potential role for temozolomide

    Energy Technology Data Exchange (ETDEWEB)

    Hardee, Matthew E. [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Formenti, Silvia C., E-mail: silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Department of Medical Oncology, New York University Langone Medical Center, New York, NY (United States)

    2012-08-09

    Brain metastases are unfortunately very common in the natural history of many solid tumors and remain a life-threatening condition, associated with a dismal prognosis, despite many clinical trials aimed at improving outcomes. Radiation therapy options for brain metastases include whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS). SRS avoids the potential toxicities of WBRT and is associated with excellent local control (LC) rates. However, distant intracranial failure following SRS remains a problem, suggesting that untreated intracranial micrometastatic disease is responsible for failure of treatment. The oral alkylating agent temozolomide (TMZ), which has demonstrated efficacy in primary malignant central nervous system tumors such as glioblastoma, has been used in early phase trials in the treatment of established brain metastases. Although results of these studies in established, macroscopic metastatic disease have been modest at best, there is clinical and preclinical data to suggest that TMZ is more efficacious at treating and controlling clinically undetectable intracranial micrometastatic disease. We review the available data for the primary management of brain metastases with SRS, as well as the use of TMZ in treating established brain metastases and undetectable micrometastatic disease, and suggest the role for a clinical trial with the aims of treating macroscopically visible brain metastases with SRS combined with TMZ to address microscopic, undetectable disease.

  10. A taxonomy of epithelial human cancer and their metastases

    Directory of Open Access Journals (Sweden)

    De Moor Bart

    2009-12-01

    Full Text Available Abstract Background Microarray technology has allowed to molecularly characterize many different cancer sites. This technology has the potential to individualize therapy and to discover new drug targets. However, due to technological differences and issues in standardized sample collection no study has evaluated the molecular profile of epithelial human cancer in a large number of samples and tissues. Additionally, it has not yet been extensively investigated whether metastases resemble their tissue of origin or tissue of destination. Methods We studied the expression profiles of a series of 1566 primary and 178 metastases by unsupervised hierarchical clustering. The clustering profile was subsequently investigated and correlated with clinico-pathological data. Statistical enrichment of clinico-pathological annotations of groups of samples was investigated using Fisher exact test. Gene set enrichment analysis (GSEA and DAVID functional enrichment analysis were used to investigate the molecular pathways. Kaplan-Meier survival analysis and log-rank tests were used to investigate prognostic significance of gene signatures. Results Large clusters corresponding to breast, gastrointestinal, ovarian and kidney primary tissues emerged from the data. Chromophobe renal cell carcinoma clustered together with follicular differentiated thyroid carcinoma, which supports recent morphological descriptions of thyroid follicular carcinoma-like tumors in the kidney and suggests that they represent a subtype of chromophobe carcinoma. We also found an expression signature identifying primary tumors of squamous cell histology in multiple tissues. Next, a subset of ovarian tumors enriched with endometrioid histology clustered together with endometrium tumors, confirming that they share their etiopathogenesis, which strongly differs from serous ovarian tumors. In addition, the clustering of colon and breast tumors correlated with clinico-pathological characteristics

  11. Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

    Science.gov (United States)

    2015-09-10

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

  12. Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

    International Nuclear Information System (INIS)

    Prokic, Vesna; Wiedenmann, Nicole; Fels, Franziska; Schmucker, Marianne; Nieder, Carsten; Grosu, Anca-Ligia

    2013-01-01

    Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 ± 0.62 Gy and 6.29 ± 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 ± 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 ± 0.7 Gy and 32.7 ± 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 ± 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

  13. Radiographic patterns and survival of patients with early and late brain metastases in EGFR wild type and mutant non small cell lung cancer

    DEFF Research Database (Denmark)

    Yuan, Ren; Yamada, Andrew; Weber, Britta

    2016-01-01

    Brain metastasis (BM) in NSCLC is a negative prognostic indicator. In the era of EGFR mutations we evaluated the difference between early (≤6 months from diagnosis) versus late BM (>6 months), in EGFR wild type (WT) and mutant (MT) NSCLC patients with respect to radiographic patterns and overall...... BM: WT 24.9 months versus MT 25.6 months (p = 0.51). In multivariate analysis chemotherapy, single lesion and late BM were associated with better survival in WT patients whereas age, and systemic treatment but not BM timing or single lesion were predictive of better outcomes in MT patients. In early...

  14. Pulmonary nodules and metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas

    2016-01-01

    Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i...

  15. SPECT and PET Serve as Molecular Imaging Techniques and in Vivo Biomarkers for Brain Metastases

    Science.gov (United States)

    Palumbo, Barbara; Buresta, Tommaso; Nuvoli, Susanna; Spanu, Angela; Schillaci, Orazio; Fravolini, Mario Luca; Palumbo, Isabella

    2014-01-01

    Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET) represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI) is discussed. PMID:24897023

  16. The effect of non-small cell lung cancer histology on survival as measured by the graded prognostic assessment in patients with brain metastases treated by hypofractionated stereotactic radiotherapy

    International Nuclear Information System (INIS)

    Ma, Liang-Hua; Li, Guang; Zhang, Hong-Wei; Wang, Zhi-Yu; Dang, Jun; Zhang, Shuo; Yao, Lei

    2016-01-01

    The purpose of this study was to investigate the impact of histology on survival stratified by the Graded Prognostic Assessment (GPA) for non-small cell lung cancer (NSCLC) in a group of selected patients treated recently. A total of 171 NSCLC patients with brain metastases treated by hypofractionated stereotactic radiotherapy with or without whole-brain radiotherapy between 2001 and 2011 were included. The GPA score was calculated for each patient. Tumor histologies were categorized into adenocarcinoma (ADCA) and non-ADCA. Median survival time (MST, in months) was calculated using the Kaplan-Meier method. The log-rank test was used to determine statistical differences. MSTs by histology were: ADCA 15 (n = 92) and non-ADCA 10 (n = 79) (p < 0.001). For all patients, the MSTs by GPA score were: GPA 3.5-4, 24; GPA 2.5-3, 15; GPA 1.5-2, 9 and GPA 0-1, 6 (p < 0.001). The histology of ADCA showed a statistically significant higher MST than non-ADCA for patients with GPA 2.5-4. For GPA 2.5-3, MSTs were: ADCA 18, non-ADCA 10 (p = 0.007); for GPA 3.5-4, MSTs were: ADCA 30, non-ADCA 17 (p = 0.046). For GPA 0-2, MSTs did not differ significantly by histology. For GPA 0-1, MSTs were: ADCA 8, non-ADCA 4 (p = 0.146); GPA 1.5-2, MSTs were: ADCA 10, non-ADCA 8 (p = 0.291). We further found that non-ADCA in upper GPA class (3.5–4) had similar survival with ADCA in lower GPA class (2.5–3) (MSTs were 17 and 18, respectively, p = 0.775). This phenomenon also happened between patients of non-ADCA in upper GPA class (2.5–3) and those of ADCA in lower GPA class (1.5–2) (MSTs were both 10, p = 0.724). We confirmed that the histology of NSCLC had effect on the GPA in these selected patients treated recently. ADCA showed a statistically significant higher MST than non-ADCA with GPA 2.5-4. The non-ADCA in upper GPA classes (3.5-4 and 2.5-3) had similar survival to ADCA in lower GPA classes (2.5-3 and 1.5-2, respectively). The histology as a new factor should be added to the original

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

    Directory of Open Access Journals (Sweden)

    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

  18. BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy

    Directory of Open Access Journals (Sweden)

    Chowdhary M

    2016-12-01

    Full Text Available Mudit Chowdhary,1,2 Kirtesh R Patel,1 Hasan H Danish,1 David H Lawson,3 Mohammad K Khan1 1Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 2Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, 3Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA Abstract: Melanoma is an aggressive malignancy that frequently spreads to the brain, resulting in rapid deterioration in both quality and quantity of life. Historically, treatment options for melanoma brain metastases (MBM have predominantly consisted of surgery and radiotherapy. While these options can help provide local control, the majority of patients still develop intracranial progression. Indeed, novel therapeutic options, including molecularly targeted agents and immunotherapy, have improved outcomes and are now changing the role of radiotherapy. Up to 50% of melanomas contain an activating BRAF mutation, resulting in hyperactive cellular proliferation and survival. Drugs that target BRAF have been introduced for the treatment of metastatic melanoma and offer hope in improving disease outcomes; however, many of these trials either excluded or had a limited amount of patients with MBM. Recent studies have revealed that melanoma cell lines become more radiosensitive following BRAF inhibition, thus providing a potential synergistic mechanism when combining BRAF inhibitor (BRAFi and radiotherapy. However, neurotoxicity concerns also exist with this combination. This article reviews the efficacy and limitations of BRAFi therapy for MBM, describes current evidence for combining BRAFis with radiation, discusses the rationale and evidence for combination modalities, and highlights emerging clinical trials specifically investigating this combination in MBM. Keywords: brain metastases, melanoma, radiation, BRAF inhibitors, vemurafenib, dabrafenib

  19. Computed tomography in evaluation of regional metastases of lung cancer

    International Nuclear Information System (INIS)

    Frolova, I.G.; Velichko, S.A.; Zyryanov, B.N.

    1999-01-01

    The rate of metastatic spread of different groups of intrathoracic lymph nodes has been studied in depending on localization of the tumor by the nodes using CT method. CT-semiotic of metastatic lymph nodes was studied. The indices of the efficiency of diagnostic imaging when using CT were analyzed as well. The analysis of data obtained has shown that CT has great possibilities in evaluation of regional metastases of lung cancer

  20. Cancer stem cells: a metastasizing menace!

    Science.gov (United States)

    Bandhavkar, Saurabh

    2016-04-01

    Cancer is one of the leading causes of death worldwide, and is estimated to be a reason of death of more than 18 billion people in the coming 5 years. Progress has been made in diagnosis and treatment of cancer; however, a sound understanding of the underlying cell biology still remains an unsolved mystery. Current treatments include a combination of radiation, surgery, and/or chemotherapy. However, these treatments are not a complete cure, aimed simply at shrinking the tumor and in majority of cases, there is a relapse of tumor. Several evidences suggest the presence of cancer stem cells (CSCs) or tumor-initiating stem-like cells, a small population of cells present in the tumor, capable of self-renewal and generation of differentiated progeny. The presence of these CSCs can be attributed to the failure of cancer treatments as these cells are believed to exhibit therapy resistance. As a result, increasing attention has been given to CSC research to resolve the therapeutic problems related to cancer. Progress in this field of research has led to the development of novel strategies to treat several malignancies and has become a hot topic of discussion. In this review, we will briefly focus on the main characteristics, therapeutic implications, and perspectives of CSCs in cancer therapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. Pulmonary nodules and metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas

    2016-01-01

    Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i...... detected in 7.5% of the patients and in 37% of these cases the metastatic spread was confined to the lungs. The prevalence of SPCM increased with the implementation of thoracic CT in CRC staging. SPCM impaired survival significantly and was associated with increasing age and rectal cancer. Resection...

  2. Radiotherapy of brain metastases and glioblastomas in elderly patients; Radiotherapie des metastases cerebrales et des glioblastomes chez le sujet age

    Energy Technology Data Exchange (ETDEWEB)

    Lauche, O.; Kerr, C.; Riou, O.; Dhermain, F. [Institut Gustave-Roussy, Villejuif (France)

    2011-10-15

    As the occurrence of malignant gliomas and brain metastases is increasing in elderly people, the authors report the definition of an optimal therapeutic strategy for these patients. For patients in good health condition, a prospective randomized showed a modest benefit of radiotherapy alone with respect to support cares in terms of survival. The radiotherapy scheme is discussed in terms of dose and number of fractions. It seems that the physiological age is a strong prognosis factor. Short communication

  3. Incidence of Leukoencephalopathy After Whole-Brain Radiation Therapy for Brain Metastases

    International Nuclear Information System (INIS)

    Ebi, Junko; Sato, Hisashi; Nakajima, Masaru; Shishido, Fumio

    2013-01-01

    Purpose: To evaluate the incidence of leukoencephalopathy after whole-brain radiation therapy (WBRT) in patients with brain metastases. Methods and Materials: We retrospectively reviewed 111 patients who underwent WBRT for brain metastases from April 2001 through March 2008 and had evaluable computed tomography (CT) and/or magnetic resonance imaging (MRI) at least 1 month after completion of WBRT. We evaluated the leukoencephalopathy according to the Common Terminology Criteria for Adverse Events, version 3.0. The patients who had brain tumor recurrence after WBRT were censored at the last follow-up CT or MRI without recurrence. To evaluate the risk factors for leukoencephalopathy, bivariate analysis was performed using a logistic regression analysis adjusted for follow-up time. Factors included in the analysis were age, gender, dose fractionation, 5-fluorouracil, methotrexate, cisplatin, and other chemotherapeutic agents. Results: The median age of the 111 patients was 60.0 years (range, 23-89 years). The median follow-up was 3.8 months (range, 1.0-38.1 months). Leukoencephalopathy developed in 23 of the 111 patients. Grades 1, 2, and 3 were observed in 8, 7, and 8 patients, respectively. The incidence was 34.4% (11 of 32), 42.9% (6 of 14), 66.7% (2 of 3), and 100% (2 of 2) of the patients who were followed up for ≥6, ≥12, ≥24, and ≥36 months, respectively. In the bivariate analysis, older age (≥65 years) was significantly correlated with higher risk of leukoencephalopathy (odds ratio 3.31; 95% confidence interval 1.15-9.50; P=.03). Conclusions: The incidence of leukoencephalopathy after WBRT was 34.4% with ≥6 months follow-up, and increased with longer follow-up. Older age was a significant risk factor. The schedule of WBRT for patients with brain metastases should be carefully determined, especially for favorable patients

  4. Cancer stem cells: a metastasizing menace!

    International Nuclear Information System (INIS)

    Bandhavkar, Saurabh

    2016-01-01

    Cancer is one of the leading causes of death worldwide, and is estimated to be a reason of death of more than 18 billion people in the coming 5 years. Progress has been made in diagnosis and treatment of cancer; however, a sound understanding of the underlying cell biology still remains an unsolved mystery. Current treatments include a combination of radiation, surgery, and/or chemotherapy. However, these treatments are not a complete cure, aimed simply at shrinking the tumor and in majority of cases, there is a relapse of tumor. Several evidences suggest the presence of cancer stem cells (CSCs) or tumor-initiating stem-like cells, a small population of cells present in the tumor, capable of self-renewal and generation of differentiated progeny. The presence of these CSCs can be attributed to the failure of cancer treatments as these cells are believed to exhibit therapy resistance. As a result, increasing attention has been given to CSC research to resolve the therapeutic problems related to cancer. Progress in this field of research has led to the development of novel strategies to treat several malignancies and has become a hot topic of discussion. In this review, we will briefly focus on the main characteristics, therapeutic implications, and perspectives of CSCs in cancer therapy

  5. 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

  6. Brain cancer spreads

    DEFF Research Database (Denmark)

    Perryman, Lara; Erler, Janine Terra

    2014-01-01

    The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue).......The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue)....

  7. Can surgical oncologists reliably predict the likelihood for non-SLN metastases in breast cancer patients?

    NARCIS (Netherlands)

    Smidt, M.L.; Strobbe, L.J.; Groenewoud, J.M.M.; Wilt, G.J. van der; Zee, K.J. van; Wobbes, Th.

    2007-01-01

    BACKGROUND: In approximately 40% of the breast cancer patients with sentinel lymph node (SLN) metastases, additional nodal metastases are detected in the completion axillary lymph node dissection (cALND). The MSKCC nomogram can help to quantify a patient's individual risk for non-SLN metastases with

  8. Mismatch repair status and synchronous metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Krarup, Peter-Martin; Morton, Dion

    2015-01-01

    The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis....... A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Group's database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial...

  9. Receptor conversion in distant breast cancer metastases

    NARCIS (Netherlands)

    Hoefnagel, L.D.C.

    2013-01-01

    The routine pathological work-up of breast cancer includes the evaluation of the estrogen receptor (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) which reveals biological information about the tumour as well as provides predictive biomarkers regarding hormonal

  10. Hilar and mediastinal lymph node metastases from lung cancer

    International Nuclear Information System (INIS)

    Koganemaru, Michihiko; Fujimoto, Kiminori; Nishimura, Hiroshi; Tabuchi, Akinori; Ohtake, Hisashi; Nishimura, Yutaka

    1990-01-01

    Sixty-one patients with primary lung cancer, who had CT and MR imaging before surgery, were studied. MR imaging used spin-echo sequences with T1 weighted image and T2 weighted image (C-MRI), and included STIR technique (Stir-MRI). The accuracy of diagnosis of mediastinal lymphadenopathy (regarding 10 mm or larger in short transverse diameter as positive) was 89% by CT, 84% by C-MRI and 89% by Stir-MRI. The accuracy of diagnosis of hilar lymphadenopathy was 42% by CT, 67% by C-MRI, and 75% by Stir-MRI. The accuracy of diagnosis of mediastinal lymph node metastases was 89% by CT, 94% by C-MRI and 96% by Stir-MRI. The accuracy of diagnosis of hilar lymph node metastases was 78% by CT, 87% by C-MRI and 89% by Stir-MRI. The possibility of enhancement of diagnostic accuracy of lymph node metastases from lung cancer was suggested by combining MR imaging including STIR technique, with CT. (author)

  11. Breast cancer metastasizing to the stomach mimicking primary gastric cancer: A case report.

    Science.gov (United States)

    Yim, Kwangil; Ro, Sang Mi; Lee, Jieun

    2017-03-28

    Breast cancer with stomach metastasis rare with an incidence of 1% or less among metastatic breast cancer patients. We experienced a case of breast cancer metastasizing to the stomach in 65-year-old female patient. She experienced dyspepsia and poor oral intake before visiting the clinic. Diffuse infiltration with nodular mucosal thickening of the stomach wall was observed, suggesting advanced gastric cancer based on gross endoscopic finding. Spread of poorly cohesive tumor cells in the gastric mucosa observed upon hematoxylin and eosin stain resembled signet ring cell carcinoma, but diffuse positive staining for GATA3 in immunohistochemical stain allowed for a conclusive diagnosis of breast cancer metastasizing to the stomach. Based on the final diagnosis, systemic chemotherapy was administered instead of primary surgical resection. After 2 cycles of docetaxel administration, she showed a partial response based on abdominal computed tomography scan. This case is an unusual presentation of breast cancer metastasizing to the gastrointestinal tract.

  12. Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids

    Science.gov (United States)

    2008-08-01

    SUBJECT TERMS Cancer therapy by localized immune response, Magneto -rehological Fluids 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...Metastasized Breast Cancer by Localized Therapy utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit Evrensel...2008 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy utilizing

  13. Mr imaging and mr spectroscopy of brain metastases by mr perfusion

    International Nuclear Information System (INIS)

    Weber, Marc-Andre; Lichy, M.P.; Thilmann, C.; Guenther, M.; Bachert, P.; Delorme, S.; Schad, L.R.; Debus, J.; Schlemmer, H.P.; Maudsley, A.A.

    2003-01-01

    In follow-up examinations of irradiated brain metastases conventional contrast-enhanced morphological MR imaging is often unable to distinguish between transient radiation effects, radionecrosis, and tumor recurrence. To evaluate changes of relative cerebral blood flow (rCBF) in irradiated brain metastases arterial spin-labeling techniques (ASL) were applied and compared to the outcome of 1 H MR spectroscopy and spectroscopic imaging ( 1 H MRS, SI). Patients and methods In 2 patients follow-up examinations of irradiated brain metastases were performed on a 1.5-T tomograph (average single dose: 20 Gy/80% isodose). Relative CBF values of gray matter (GM), white matter (WM), and metastases (Met) were measured by means of the ASL techniques ITS-FAIR and Q2TIPS. 1 H MRS was performed with PRESS 1500/135. In both patients with initially hyperperfused metastases (Met/GM >1) the reduction of rCBF after stereotactic radiosurgery indicated response to treatment - even if the contrast-enhancing region increased - while increasing rCBF values indicated tumor progression. The findings were confirmed by 1 H MRS, SI and subsequent follow-up. The ASL techniques ITS-FAIR and Q2TIPS are able to monitor changes of rCBF in irradiated brain metastases. The two cases imply a possible role for ASL-MR perfusion imaging and 1 H MR spectroscopy in differentiating radiation effects from tumor progression. (orig.) [de

  14. Diazepam prophylaxis of contrast media-induced seizures during computed tomography of patients with brain metastases

    International Nuclear Information System (INIS)

    Pagani, J.J.; Hayman, L.A.; Bigelow, R.H.; Libshitz, H.I.; Lepke, R.A.; Wallace, S.

    1983-01-01

    The effect of 5 mg of intravenous diazepam (Valium) on contrast media-associated seizer incidence was studied in a randomized controlled trial involving 284 patients with known or suspected brain metastases undergoing cerebral computed tomography. Of these patients, 188 were found to have brain metastases, and it is estimated that for this subgroup prophylactic diazepam reduces the risk of contrast-assocated seizure by a factor of 0.26. Seizures occurred in three of 96 patients with metastases on diazepam and in 14 of 92 patients with metastases but without diazepam. Factors related to increased risk of contrast media-associated seizures are: (1) prior seizure history due to brain metatases and/or prior contrast, (2) progressive cerebral metastases, and (3) prior or concurrent brain antineoplastic therapy. Factors not related to an increased risk of these seizures are: (1) contrast media dosage, chemical composition, or osmolarity, (2) computed tomographic appearance of metastases, and (3) type of primary malignancy. Concomitant therapeutic levels of diphenylhydantoin (Dilantin) do not protect completely against contrast media-associated seizures. Pathophysiology of contrast media-associated seizures is discussed in view of the risk factors determined by this study

  15. CT findings of small bowel metastases from primary lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Wook; Ha, Hyun Kwon; Kim, Ah Young; Kim, Gab Choul; Kim, Tae Kyoung; Kim, Pyo Nyun; Lee, Moon Gyu [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2002-11-01

    To evaluate the CT findings of small bowel metastases from primary lung cancer. Of the 1468 patients with primary lung cancer between 1990 and 2000, 13 patients who had metastasis to the small intestine were collected. Of these 13 patients, nine who underwent CT scan were included for analysis. The pathologic diagnoses of primary lung cancer in these nine patients were squamous cell carcinoma in six, adenocarcinoma in two, and large cell carcinoma in one. CT scans were analyzed with regard to the site and patterns (intraluminal mass/bowel wall thickening/bowel implants) of metastatic masses, and the presence or absence of complication such as intussusception, obstruction, or perforation of the small bowel. The medical records of the patients were also reviewed retrospectively for evaluation of presenting abdominal symptom and time interval of metastases from initial diagnosis of lung cancer. Metastatic lesions were distributed throughout the small intestine: the duodenum in five, the jejunum in four, the ileum in six, and both jejunum and ileum in one patient. The size of metastatic masses of small bowel ranged from 1.3 cm to 5.0 cm (mean size, 2.6 cm) On CT, the small bowel was involved with intraluminal masses (mean size, 3.4 cm) in eight patients, diffuse wall thickening (mean thickness, 1.6 cm) in five, and bowel implants (mean size, 2.2 cm) in two. Complications occurred in seven patients, including intussusceptions without obstruction in two patients and with obstruction in two, obstruction without intussusceptions in two, and bowel perforation in one. Of 9 patients, 6 had at least one symptom referable to the small bowel including abdominal pain in 4, anemia in 3, vomiting in 1, and jaundice in 1. Lung cancer and small bowel lesions were detected simultaneously in four patients and the time interval of metastases from initial diagnosis of lung cancer ranged from 10 days to 30 months (median interval, 54 days) in patients. CT helps in defining the extent and

  16. CT findings of small bowel metastases from primary lung cancer

    International Nuclear Information System (INIS)

    Kim, Jae Wook; Ha, Hyun Kwon; Kim, Ah Young; Kim, Gab Choul; Kim, Tae Kyoung; Kim, Pyo Nyun; Lee, Moon Gyu

    2002-01-01

    To evaluate the CT findings of small bowel metastases from primary lung cancer. Of the 1468 patients with primary lung cancer between 1990 and 2000, 13 patients who had metastasis to the small intestine were collected. Of these 13 patients, nine who underwent CT scan were included for analysis. The pathologic diagnoses of primary lung cancer in these nine patients were squamous cell carcinoma in six, adenocarcinoma in two, and large cell carcinoma in one. CT scans were analyzed with regard to the site and patterns (intraluminal mass/bowel wall thickening/bowel implants) of metastatic masses, and the presence or absence of complication such as intussusception, obstruction, or perforation of the small bowel. The medical records of the patients were also reviewed retrospectively for evaluation of presenting abdominal symptom and time interval of metastases from initial diagnosis of lung cancer. Metastatic lesions were distributed throughout the small intestine: the duodenum in five, the jejunum in four, the ileum in six, and both jejunum and ileum in one patient. The size of metastatic masses of small bowel ranged from 1.3 cm to 5.0 cm (mean size, 2.6 cm) On CT, the small bowel was involved with intraluminal masses (mean size, 3.4 cm) in eight patients, diffuse wall thickening (mean thickness, 1.6 cm) in five, and bowel implants (mean size, 2.2 cm) in two. Complications occurred in seven patients, including intussusceptions without obstruction in two patients and with obstruction in two, obstruction without intussusceptions in two, and bowel perforation in one. Of 9 patients, 6 had at least one symptom referable to the small bowel including abdominal pain in 4, anemia in 3, vomiting in 1, and jaundice in 1. Lung cancer and small bowel lesions were detected simultaneously in four patients and the time interval of metastases from initial diagnosis of lung cancer ranged from 10 days to 30 months (median interval, 54 days) in patients. CT helps in defining the extent and

  17. Tyrosine kinase inhibitors show different anti-brain metastases efficacy in NSCLC: A direct comparative analysis of icotinib, gefitinib, and erlotinib in a nude mouse model.

    Science.gov (United States)

    Tan, Jianlong; Li, Min; Zhong, Wen; Hu, Chengping; Gu, Qihua; Xie, Yali

    2017-11-17

    Brain metastasis is an increasing problem in non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs), including gefitinib, erlotinib, and icotinib, are reported to be effective in patients with brain metastases. However, direct comparative studies of the pharmacokinetics and efficacy of these three drugs in treating brain metastases are lacking. In the present investigation, we found that gefitinib penetrated the blood-tumor barrier and was distributed to brain metastases more effectively than erlotinib or icotinib in a nude mouse model. The 1-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 9.82±1.03%, 4.83±0.25%, and 2.62±0.21%, respectively. The 2-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 15.11±2.00%, 5.73±1.31%, and 2.69±0.31%, respectively. Gefitinib exhibited the strongest antitumor activity ( p gefitinib vs. erlotinib =0.005; p gefitinib vs. icotinib =0.002). Notably, erlotinib exhibited a better treatment efficacy than icotinib ( p =0.037). Consistently, immunohistochemical data showed that TKIs differentially inhibit the proliferation of metastatical tumor cells. Gefitinib and erlotinib markedly inhibited the proliferation of tumor cells, while there were more ki-67-positive tumor cells in the icotinib group. Additionally, gefitinib inhibited the phosphorylation of EGFR better than the other drugs, whereas pEGFR expression levels in erlotinib groups were lower than levels in the icotinib group ( p gefitinib vs. erlotinib =0.995; p gefitinib vs. icotinib =0.028; p erlotinib vs. icotinib =0.042).Altogether, our findings suggest that gefitinib and erlotinib can inhibit the growth of PC-9-luc brain tumors. Gefitinib demonstrated better antitumor activity and penetration rate in brain metastases than erlotinib or icotinib.

  18. A Phase 2 Trial of Stereotactic Radiosurgery Boost After Surgical Resection for Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Brennan, Cameron [Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yang, T. Jonathan [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Hilden, Patrick; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chan, Kelvin; Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chan, Timothy A. [Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lymberis, Stella C. [Department of Radiation Oncology, New York University Langone Medical Center, New York, New York (United States); Narayana, Ashwatha [Department of Radiation Oncology, Greenwich Hospital, Greenwich, Connecticut (United States); Tabar, Viviane; Gutin, Philip H. [Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Ballangrud, Åse [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lis, Eric [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beal, Kathryn, E-mail: BealK@MSKCC.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-01-01

    Purpose: To evaluate local control after surgical resection and postoperative stereotactic radiosurgery (SRS) for brain metastases. Methods and Materials: A total of 49 patients (50 lesions) were enrolled and available for analysis. Eligibility criteria included histologically confirmed malignancy with 1 or 2 intraparenchymal brain metastases, age ≥18 years, and Karnofsky performance status (KPS) ≥70. A Cox proportional hazard regression model was used to test for significant associations between clinical factors and overall survival (OS). Competing risks regression models, as well as cumulative incidence functions, were fit using the method of Fine and Gray to assess the association between clinical factors and both local failure (LF; recurrence within surgical cavity or SRS target), and regional failure (RF; intracranial metastasis outside of treated volume). Results: The median follow-up was 12.0 months (range, 1.0-94.1 months). After surgical resection, 39 patients with 40 lesions were treated a median of 31 days (range, 7-56 days) later with SRS to the surgical bed to a median dose of 1800 cGy (range, 1500-2200 cGy). Of the 50 lesions, 15 (30%) demonstrated LF after surgery. The cumulative LF and RF rates were 22% and 44% at 12 months. Patients who went on to receive SRS had a significantly lower incidence of LF (P=.008). Other factors associated with improved local control include non-small cell lung cancer histology (P=.048), tumor diameter <3 cm (P=.010), and deep parenchymal tumors (P=.036). Large tumors (≥3 cm) with superficial dural/pial involvement showed the highest risk for LF (53.3% at 12 months). Large superficial lesions treated with SRS had a 54.5% LF. Infratentorial lesions were associated with a higher risk of developing RF compared to supratentorial lesions (P<.001). Conclusions: Postoperative SRS is associated with high rates of local control, especially for deep brain metastases <3 cm. Tumors ≥3 cm with superficial dural

  19. Diffusion-weighted imaging of brain metastases: their potential to be misinterpreted as focal ischaemic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Geijer, B. [Department of Radiology, University Hospital, Lund (Sweden); Holtaas, S. [Department of Diagnostic Imaging, King Fahd Hospital, Riyadh (Saudi Arabia)

    2002-07-01

    Small focal ischaemic brain lesions are said to be easy to identify in the acute stage and to differentiate from older lesions using diffusion-weighted imaging (DWI). Brain metastases are common and the aim of this study was to evaluate the risk of misinterpretation as ischaemic lesions in a standard MRI protocol for clinical stroke. Of 26 patients investigated with MRI for possible metastases, 12 did have metastatic brain lesions, including most of the common tumours. On a 1.5 tesla imager, we obtained DWI, plus T2- and T1-weighted images, the latter before and after triple-dose contrast medium. Well-circumscribed brain lesions with a decreased apparent diffusion coefficient and a slightly or moderately increased signal on T2-weighted images were found in patients with metastases from a small-cell bronchial carcinoma and a pulmonary adenocarcinoma. The same features were also found in metastases from a breast carcinoma but the lesions were surrounded by oedema. With a standard DWI protocol, the features of common brain metastases may overlap with those of small acute and subacute ischaemic lesions. (orig.)

  20. Clodronate Therapy in Patients with Breast Cancer and Bone Metastases

    International Nuclear Information System (INIS)

    Saber, M.M.; Shouman, T.

    2003-01-01

    To assess whether clodronate can reduce frequency of skeletal morbidity in women with lytic bone metastases from breast cancer. Methods: Between 1997 and 2001,167 patients with stage IV breast cancer with bone metastases, were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for 12 months, in addition to the standard specific anti cancer therapy (87 patients) or standard anti cancer therapy only (80 patients). Skeletal complications, including pathological fractures, the need for radiation to bone or bone surgery, spinal cord compression and hypercalcaemia (a serum calcium concentration above 12 mg per deci liter (3.0 mmol per liter) or elevated to any degree and requiring treatment) were assessed monthly. Bone pam. use of analgesic drugs, performance status and quality of life were assessed throughout the trial. Results: There was no significant difference between the two groups at study entry regarding clinical characteristics. The median time for first skeletal complication was ,significantly less in the control group (6.1 vs 9.7 months, ρ=0.05). The proportion of patients who had any skeletal complication in the clodronate group than the control group, but the difference was insignificant (ρ 0.09). Clodronate was generally well tolerated and the main side effects were constipation (32%) flatulence/dyspepsia (17%) and anorexia (8%). The overall survival was not affected by clodronate therapy. The median survival was 14 months In the clodronate group and 13.8 months in the control group. Conclusions: Clodronate is an effective supplement to conventional anticancer treatment for breast cancer with bone metastasis. It reduces skeletal complications and relieves symptoms associated with lytic bone lesions. Further clinical trials that recruit a larger number of patients will be needed to clearly define the role of clodronate in metastatic breast cancer

  1. Gamma Knife Radiosurgery for Treatment of Cerebral Metastases From Non–Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Motta, Micaela; Vecchio, Antonella del; Attuati, Luca; Picozzi, Piero; Perna, Lucia; Franzin, Alberto; Bolognesi, Angelo; Cozzarini, Cesare; Calandrino, Riccardo; Mortini, Pietro; Muzio, Nadia di

    2011-01-01

    Purpose: To evaluate clinical and physico-dosimetric variables affecting clinical outcome of patients treated with Gamma Knife radiosurgery (GKRS) for brain metastases from non–small cell lung cancer (NSCLC). Methods and Materials: Between 2001 and 2006, 373 patients (298 men and 75 women, median age 65 years) with brain metastases from NSCLC underwent GKRS. All of them had KPS ≥ 60%, eight or fewer brain metastases, confirmed histopathological diagnosis and recent work-up ( 3 . Median marginal dose was 22.5 Gy at 50% isodose.; median 10 Gy and 12 Gy isodose volumes were 30.8 cm 3 and 15.8 cm 3 , respectively. Follow-up with MRI was performed every 3 months. Overall survival data were collected from internal database, telephone interviews, and identifying registries. Results: Mean follow-up after GKRS was 51 months (range, 6 to 96 months); mean overall survival was 14.2 months. Of 373 patients, 29 were alive at time of writing, 104 had died of cerebral progression, and 176 had died of systemic progression. In 64 cases it was not possible to ascertain the cause. Univariate and multivariate analysis were adjusted for the following: RPA class, surgery, WBRT, age, gender, number of lesions, median tumor volume, median peripheral dose, and 10 Gy and 12 Gy volumes. Identified RPA class and overall tumor volume >5 cc were the only two covariates independently predictive of overall survival in patients who died of cerebral progression. Conclusions: Global volume of brain disease should be the main parameter to consider for performing GKRS, which is a first-line therapy for patient in good general condition and controlled systemic disease.

  2. ANALYSIS OF RELAPSE RATE AND METASTASES OF HIGH DIFFERENTIATED THYROID CANCER

    Directory of Open Access Journals (Sweden)

    E. V. Savenok

    2015-01-01

    Full Text Available  Analysis of rate of relapses and metastases with well-differentiated thyroid cancer was performed for patients in 2009 to 2013. The study involved 189 patients with thyroid cancer including 98 (51.9 % patients suffering from papillary thyroid cancer, 77 (40.7 % patients suffering from follicular thyroid cancer, and 14 (7.4 % patients suffering from medullary thyroid cancer. 2.04 % of the 98 patients suffering from papillary thyroid cancer manifested a relapse, and lymphogenic metastases of cancer were revealed with 1.0 % of patients. With follicular thyroid cancer (n = 77, lymphogenic metastases were registered in 7.8 % of cases, relapses were revealed in 1.3 % of cases. This analysis demonstrated that observation of patients for 5 years revealed a higher percentage of metastases with patients that suffered from follicular thyroid cancer.

  3. Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Trude G. Simonsen

    2016-06-01

    Full Text Available INTRODUCTION: A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. METHODS: A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. RESULTS: Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. CONCLUSION: Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases.

  4. Survival and prognostic factors in patients treated with stereotactic radiotherapy for brain metastases

    DEFF Research Database (Denmark)

    Leth, Thomas; Oettingen, Gorm von; Lassen-Ramshad, Yasmin A.

    2015-01-01

    Abstract Background. Stereotactic radiation therapy (SRT) of brain metastases is used with good effect around the world, but no consensus exists regarding which prognostic factors that are related to favourable or unfavourable prognosis after the treatment. A better definition of these factors...... will ensure a more precise application of the treatment. Material and methods. A consecutive cohort of the 198 patients treated for brain metastases with SRT without concurrent whole-brain radiation therapy at our department from 2001 to 2012 was retrospectively analysed. Results. Median survival was seven...... months and median time to clinical cerebral progression was eight months. The multivariate analysis revealed age ≥ 65 years, Performance Status ≥ 2, extracranial metastases and size of metastasis > 20 mm as independent prognostic factors related to shorter survival. No factors were independently related...

  5. Whole brain radiotherapy for brain metastases: The technique of irradiation influences the dose to parotid glands

    International Nuclear Information System (INIS)

    Loos, G.; Paulon, R.; Verrelle, P.; Lapeyre, M.

    2012-01-01

    In the treatment of brain metastases, whole brain radiotherapy can be carried out according two distinct methods: one using multi-leaf collimator for field shaping and protection of organs at risk, and a second one is to make a rotation of the field to avoid the eyes. The aim of the study was to compare for 10 patients the dose distributions at organs at risk for each method. Patients received 30 Gy in 10 fractions. Except for parotid glands, the dose received by organs at risk and the planning target volume was the same with each method. For whole brain radiotherapy, excluding the cisterna cerebellomedullaris, the mean parotid dose was 9.63 Gy using the multi-leaf collimator versus 12.32 Gy using the field rotation (P = 0.04). For whole brain radiotherapy including the cisterna cerebellomedullaris, the mean parotid dose was 11.12 Gy using the multi-leaf collimator versus 20.06 Gy using field rotation (P < 0.001). Using the multi-leaf collimator seems recommended for whole brain radiotherapy, to reduce the dose to the parotids. (authors)

  6. Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids. Addendum

    Science.gov (United States)

    2009-08-01

    Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit A. Evrensel...AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible... Magneto -rheological Fluid (MRF) iron nano-particles were synthesized using the reverse micelle technique and coated with poly(NIPAAm). The size

  7. Gamma knife radiosurgery for ten or more brain metastases. Analysis of the whole brain irradiation doses

    International Nuclear Information System (INIS)

    Nakaya, Kotaro; Hori, Tomokatsu; Izawa, Masahiro; Yamamoto, Masaaki

    2002-01-01

    Gamma knife (GK) radiosurgery has recently been recognized as the most powerful treatment modality in managing patients with brain metastasis, be they radioresistant or not, solitary or multiple. Very recently, this treatment has been employed in patients with numerous brain metastases, even those with 10 or more lesions. However, cumulative irradiation doses to the whole brain, with such treatment, remain unknown. Since the Gamma Plan ver. 5.10 (ver. 5.30 is presently available, Leksell Gamma Plan) became available in November, 1998, 105 GK procedures have been performed at our two facilities, Tokyo Women's Medical University and Katsuta Hospital Mito Gamma House. The median lesion number was 17, ranging 10-43, and the median cumulative volume of all tumors was 8.72 cm 3 , ranging 0.41-81.41 cm 3 . The selected doses at the lesion periphery ranged 12-25 Gy, the median being 20 Gy. Based on these treatment protocols, the cumulative irradiation dose was computed. The median cumulative irradiation dose to the whole brain was 4.83, ranging 2.16-8.51 Gy: the median integrated dose to the whole brain was 6.2 J, ranging 2.16-11.9 J. The median brain volumes receiving ≥2, ≥5, ≥10, ≥15 and ≥20 Gy were 1105 (range: 410-1501), 309 (46-1247), 64 (13-282), 24 (2-77), and 8 (0-40) cm 3 , respectively. The cumulative whole brain irradiation doses for patients with numerous radiosurgical targets were considered not to exceed the threshold level of normal brain necrosis. (author)

  8. Hemorrhagic brain metastases with high signal intensity on diffusion-weighted MR images. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Mori, H.; Abe, O.; Aoki, S.; Masumoto, T.; Yoshikawa, T.; Kunimatsu, A; Hayashi, N.; Ohtomo, K. [Graduate School of Medicine, Univ. of Tokyo (Japan). Dept. of Radiology

    2002-11-01

    Diffusion-weighted MR imaging has been applicable to the differential diagnosis of abscesses and necrotic or cystic brain tumors. However, restricted water diffusion is not necessarily specific for brain abscess. We describe ring-enhancing metastases of lung carcinoma characterized by high signal intensity on diffusion-weighted MR images. The signal pattern probably reflected intralesional hemorrhage. The present report adds to the growing literature regarding the differential diagnosis of ring-enhancing brain lesions.

  9. Radiosurgery for brain metastases at the Royal Adelaide Hospital: are we treating the right patients?

    International Nuclear Information System (INIS)

    Roos, D.E.; Brophy, B.P.; Zavgorodni, S.F.; Katsilis, E.S.

    2002-01-01

    Although non-randomized data strongly suggest improved outcome from radiosurgery (RS) for brain metastases relative to whole brain radiotherapy (WBRT) alone, selection factors account for much of the observed differences. This retrospective review of the 16 brain metastases patients treated so far with RS at the Royal Adelaide Hospital confirms a median survival of 10.1 months, consistent with recent multi-institutional pooled results and significantly longer than the median survival of 3-6 months typically reported for WBRT alone. The emerging randomized trials comparing surgery, RS and WBRT for brain metastases are reviewed in the context of the Radiation Therapy Oncology Group Recursive Partitioning Analysis prognostic Class concept in order to assess whether we are using this resource intensive technique to treat the 'right' patients. We conclude that it is reasonable to continue our current policy of considering RS primarily for patients of good performance status with solitary brain metastases. VVe have a flexible approach to adjuvant WBRT which appears to decrease brain relapse, but not improve survival. Copyright (2002) Blackwell Science Pty Ltd

  10. Metastatic disease of the brain: extra-axial metastases (skull, dura, leptomeningeal) and tumour spread

    Energy Technology Data Exchange (ETDEWEB)

    Maroldi, Roberto; Ambrosi, Claudia; Farina, Davide [University of Brescia, Department of Radiology, Brescia, BS (Italy)

    2005-03-01

    Extra-axial intracranial metastases may arise through several situations. Hematogenous spread to the meninges is the most frequent cause. Direct extension from contiguous extra-cranial neoplasms, secondary invasion of the meninges by calvarium and skull base metastases, and migration along perineural or perivascular structures are less common. Leptomeningeal invasion gives rise to tumour cell dissemination by the cerebrospinal fluid (CSF), eventually leading to neoplastic coating of brain surfaces. Contrast-enhanced magnetic resonance (MR) imaging is complementary to CSF examinations and can be invaluable, detecting up to 50% of false-negative lumbar punctures. MR findings range from diffuse linear leptomeningeal enhancement to multiple enhancing extra-axial nodules, obstructive communicating and non-communicating hydrocephalus. Both calvarial and epidural metastases infrequently transgress the dura, which acts as a barrier against tumour spread. Radionuclide bone studies are still a valuable screening test to detect bone metastases. With computed tomography (CT) and MR, bone metastases extending intracranially and primary dural metastases show the characteristic biconvex shape, usually associated with brain displacement away from the inner table. Although CT is better in detecting skull base erosion, MR is more sensitive and provides more detailed information about dural involvement. Perineural and perivascular spread from head and neck neoplasms require thin-section contrast-enhanced MR. (orig.)

  11. SPECT and PET Serve as Molecular Imaging Techniques and in Vivo Biomarkers for Brain Metastases

    Directory of Open Access Journals (Sweden)

    Barbara Palumbo

    2014-06-01

    Full Text Available Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI is discussed.

  12. Management of lung cancer brain metastasis: An overview

    Directory of Open Access Journals (Sweden)

    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.

  13. Do patients with a limited number of brain metastases need whole-brain radiotherapy in addition to radiosurgery?

    International Nuclear Information System (INIS)

    Rades, D.; Schild, S.E.

    2012-01-01

    Background: About 40% of patients with brain metastases have a very limited number of lesions and may be candidates for radiosurgery. Radiosurgery alone is superior to whole-brain radiotherapy (WBRT) alone for control of treated and new brain metastases. In patients with a good performance status, radiosurgery also resulted in better survival. However, the question is whether the results of radiosurgery alone can be further improved with additional WBRT. Methods: Information for this review was compiled by searching the PubMed and MEDLINE databases. Very important published meeting abstracts were also considered. Results: Based on both retrospective and prospective studies, the addition of WBRT to radiosurgery improved control of treated and new brain metastases but not survival. However, because a recurrence within the brain has a negative impact on neurocognitive function, it is important to achieve long-term control of brain metastases. Conclusion: The addition of WBRT provides significant benefits. Further randomized studies including adequate assessment of neurocognitive function and a follow-up period of at least 2 years are needed to help customize the treatment for individual patients. (orig.)

  14. 18F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    International Nuclear Information System (INIS)

    Yu, Chunjing; Mi, Baoming; Wan, Weixing; Pan, Donghui; Xu, Yuping; Yang, Min; Lang, Lixin; Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    We report the biodistribution and radiation dosimetry of an integrin α v β 3 specific PET tracer 18 F-AlF-NOTA-E[PEG 4 -c(RGDfk)] 2 (denoted as 18 F-Alfatide II). We also assessed the value of 18 F-Alfatide II in patients with brain metastases. A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of 18 F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with 18 F-FDG (5.55 MBq/kg) and 18 F-Alfatide II. Injection of 18 F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. 18 F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by 18 F-Alfatide II PET, while only ten lesions were visualized by 18 F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that 18 F-Alfatide II is feasible for human studies. 18 F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  15. Sanctuary site leptomeningeal metastases in HER-2 positive breast cancer: A review in the era of trastuzumab.

    Science.gov (United States)

    Kordbacheh, T; Law, W Y; Smith, I E

    2016-04-01

    The development of trastuzumab and other targeted systemic therapies has transformed the management of HER-2 positive breast cancers. However, as patients live longer and systemic therapies may not cross the blood brain barrier a rising number of patients are developing leptomeningeal metastases and brain metastases as a sanctuary site of disease. Intrathecal trastuzumab has been reported to treat these. We describe a breast cancer patient with HER-2 positive leptomeningeal disease in the spinal cord successfully treated with intrathecal trastuzumab and methotrexate, alongside systemic anti-HER-2 therapy and radiotherapy. We also review the literature to date on the efficacy and safety of intrathecal trastuzumab, and recent evidence suggesting that intrathecal trastuzumab passes via the blood brain barrier into the serum to achieve intravenous concentrations similar to that seen with systemic therapy alone. Overall, intrathecal trastuzumab appears to be a safe and often effective treatment for leptomeningeal metastases in HER-2 positive breast cancer. Ongoing phase I and II studies are required to determine optimum dosing schedules, validate CSF and CSF-to-serum pharmacokinetics, determine efficacy, and to assess the added benefits or disadvantages of prior radiotherapy and concomitant systemic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. A deep convolutional neural network-based automatic delineation strategy for multiple brain metastases stereotactic radiosurgery.

    Directory of Open Access Journals (Sweden)

    Yan Liu

    Full Text Available Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS treatment planning. In this work, we developed a deep learning convolutional neural network (CNN algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases.

  17. Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases

    International Nuclear Information System (INIS)

    Steinmann, Diana; Gerstein, Johanna; Gharbi, Nadine; Hagg, Juliane; Hipp, Matthias; Kleff, Irmgard; Müller, Axel; Schäfer, Christof; Schleicher, Ursula; Sehlen, Susanne; Theodorou, Marilena; Paelecke-Habermann, Yvonne; Wypior, Hans-Joachim; Zehentmayr, Franz; Oorschot, Birgitt van; Vordermark, Dirk; Geinitz, Hans; Aschoff, Raimund; Bayerl, Anja; Bölling, Tobias; Bosch, Elisabeth; Bruns, Frank; Eichenseder-Seiss, Ute

    2012-01-01

    Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information

  18. Radiosurgery alone for 5 or more brain metastases: expert opinion survey.

    Science.gov (United States)

    Knisely, Jonathan P S; Yamamoto, Masaaki; Gross, Cary P; Castrucci, William A; Jokura, Hidefumi; Chiang, Veronica L S

    2010-12-01

    Oligometastatic brain metastases may be treated with stereotactic radiosurgery (SRS) alone, but no consensus exists as to when SRS alone would be appropriate. A survey was conducted at 2 radiosurgery meetings to determine which factors SRS practitioners emphasize in recommending SRS alone, and what physician characteristics are associated with recommending SRS alone for ≥ 5 metastases. All physicians attending the 8th Biennial Congress and Exhibition of the International Stereotactic Radiosurgery Society in June 2007 and the 18th Annual Meeting of the Japanese Society of Stereotactic Radiosurgery in July 2009 were asked to complete a questionnaire ranking 14 clinical factors on a 5-point Likert-type scale (ranging from 1 = not important to 5 = very important) to determine how much each factor might influence a decision to recommend SRS alone for brain metastases. Results were condensed into a single dichotomous outcome variable of "influential" (4-5) versus "not influential" (1-3). Respondents were also asked to complete the statement: "In general, a reasonable number of brain metastases treatable by SRS alone would be, at most, ___." The characteristics of physicians willing to recommend SRS alone for ≥ 5 metastases were assessed. Chi-square was used for univariate analysis, and logistic regression for multivariate analysis. The final study sample included 95 Gamma Knife and LINAC-using respondents (54% Gamma Knife users) in San Francisco and 54 in Sendai (48% Gamma Knife users). More than 70% at each meeting had ≥ 5 years experience with SRS. Sixty-five percent in San Francisco and 83% in Sendai treated ≥ 30 cases annually with SRS. The highest number of metastases considered reasonable to treat with SRS alone in both surveys was 50. In San Francisco, the mean and median numbers of metastases considered reasonable to treat with SRS alone were 6.7 and 5, while in Sendai they were 11 and 10. In the San Francisco sample, the clinical factors identified to be

  19. Whole brain irradiation in case of brain metastases in from 2005 to 2011 in the clinic for nuclear medicine of the university hospital Freiburg

    International Nuclear Information System (INIS)

    Hintz, Mandy

    2017-01-01

    Brain metastases are the largest group of brain tumors. Their occurrence influences the overall survival and the quality of life. The retrospective study deals with the overall survival, the local tumor control and the prognostic factors of patients treated with whole brain irradiation. The data were evaluated using multivariate analysis. Whole brain irradiation has shown to be an efficient therapy option for patients with brain metastases and has the possibility to improve the overall progress-free survival and the symptom control.

  20. Predictors of Distant Brain Recurrence for Patients With Newly Diagnosed Brain Metastases Treated With Stereotactic Radiosurgery Alone

    International Nuclear Information System (INIS)

    Sawrie, Stephen M.; Guthrie, Barton L.; Spencer, Sharon A.; Nordal, Robert A.; Meredith, Ruby F.; Markert, James M.; Cloud, Gretchen A.; Fiveash, John B.

    2008-01-01

    Purpose: To ascertain predictors of distant brain failure (DBF) in patients treated initially with stereotactic radiosurgery alone for newly diagnosed brain metastases. We hypothesize that these factors may be used to group patients according to risk of DBF. Methods and Materials: We retrospectively analyzed 100 patients with newly diagnosed brain metastases treated from 2003 to 2005 at our Gamma Knife radiosurgery facility. The primary endpoint was DBF. Potential predictors included number of metastases, tumor volume, histologic characteristics, extracranial disease, and use of temozolomide. Results: One-year actuarial risk of DBF was 61% for all patients. Significant predictors of DBF included more than three metastases (hazard ratio, 3.30; p = 0.004), stable or poorly controlled extracranial disease (hazard ratio, 2.16; p = 0.04), and melanoma histologic characteristics (hazard ratio, 2.14; p = 0.02). These were confirmed in multivariate analysis. Those with three or fewer metastases, no extracranial disease, and nonmelanoma histologic characteristics (N = 18) had a median time to DBF of 89 weeks vs. 33 weeks for all others. One-year actuarial freedom from DBF for this group was 83% vs. 26% for all others. Conclusions: Independent significant predictors of DBF in our series included number of metastases (more than three), present or uncontrolled extracranial disease, and melanoma histologic characteristics. These factors were combined to identify a lower risk subgroup with significantly longer time to DBF. These patients may be candidates for initial localized treatment, reserving whole-brain radiation therapy for salvage. Patients in the higher risk group may be candidates for initial whole-brain radiation therapy or should be considered for clinical trials

  1. Percutaneous Thermal Ablation of Breast Cancer Metastases in Oligometastatic Patients

    Energy Technology Data Exchange (ETDEWEB)

    Barral, M., E-mail: matthias-barral@yahoo.fr [Institut Gustave Roussy, Interventional Radiology Department (France); Auperin, A., E-mail: anne.auperin@gustaveroussy.fr [Institut Gustave Roussy, Biostatistics and Epidemiology Unit (France); Hakime, A., E-mail: thakime@yahoo.com; Cartier, V., E-mail: victoirecartier@hotmail.com; Tacher, V., E-mail: vaniatacher@gmail.com [Institut Gustave Roussy, Interventional Radiology Department (France); Otmezguine, Yves, E-mail: yotmezguine@ccps.com [Centre Clinique de la Porte de Saint-Cloud, Radiotherapy (France); Tselikas, L., E-mail: lambros.tselikas@gmail.com; Baere, T. de, E-mail: thierry.debaere@gustaveroussy.fr; Deschamps, F., E-mail: frederic.deschamps@gustaveroussy.fr [Institut Gustave Roussy, Interventional Radiology Department (France)

    2016-06-15

    ObjectiveTo evaluate prognostic factors associated with local control and disease-free-survival (DFS) of oligometastatic breast cancer patients treated by percutaneous thermal ablation (PTA).Materials and MethodsSeventy-nine consecutive patients (54.5 ± 11.2 years old) with 114 breast cancer metastases (28.9 ± 16.1 mm in diameter), involving the lungs, the liver, and/or the bone, were treated using PTA with a curative intent. The goal was to achieve a complete remission in association with systemic chemotherapy and hormonal therapy. We retrospectively evaluated the prognostic factors associated with 1- and 2-year local control and the 1- and 2-year DFS rates.ResultsThe 1- and 2-year local control rates were 83.0 and 76.1 %, respectively. Tumor burden was associated with a poorer outcome for local control after PTA (HR 1.027 by additional millimeter, p = 0.026; >4 cm HR 3.90). The 1- and 2-year DFS rates were 54.2 and 30.4 %, respectively. In multivariate analysis, triple-negative histological subtype and increased size of treated metastases were associated with a poorer DFS (HR 2.22; 95 % CI [1.13–4.36]; p = 0.02 and HR 2.43; 95 % CI [1.22–4.82]; p = 0.011, respectively).ConclusionPTA is effective for local control of breast cancer oligometastases. Tumor burden >4 cm and triple-negative histological subtype are associated with a poorer outcome.

  2. 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.

  3. Unresectable liver metastases in colorectal cancer: review of current strategies.

    Science.gov (United States)

    Sueur, Benjamin; Pellerin, Olivier; Voron, Thibault; Pointet, Anne L; Taieb, Julien; Pernot, Simon

    2016-12-01

    The objective of the treatment of colorectal cancer patients with unresectable liver metastases should be clearly defined at the outset. Potentially resectable patients should be distinguished from clearly unresectable patients. In defining resectability, it is important to take into account both anatomic characteristics and patient characteristic (comorbidities, symptoms, age). According to this evaluation, treatment should be tailored to each patient. The most widely accepted standard is doublet cytotoxic regimen plus biotherapy (anti-EGFR or anti-VEGF antibodies according to RAS status, but some patients could benefit from an intensified regimen, as triplet chemotherapy ± bevacizumab, or intraarterial treatments (hepatic arterial infusion, radioembolization or chemoembolization), in order to allow resectability. It is therefore very important to discuss the treatments with a multidisciplinary team, including an experienced surgeon, an interventional radiologist and an oncologist. On the other hand, some patients could benefit in terms of quality of life and decreased toxicity from less intense treatment when resection is not an objective. First-line monotherapy or a maintenance strategy with biotherapy and/or cytotoxics could be discussed with these patients, and treatment holidays should be considered in selected patients. Finally, in patients with secondary resection of liver metastases, specificity should be considered in choosing the best adjuvant treatment, such as response to preoperative treatment and individual risk of relapse, which many in some cases justify intensification with hepatic arterial infusion in an adjuvant setting.

  4. Risks of postoperative paresis in motor eloquently and non-eloquently located brain metastases

    International Nuclear Information System (INIS)

    Obermueller, Thomas; Schaeffner, Michael; Gerhardt, Julia; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

    2014-01-01

    When treating cerebral metastases all involved multidisciplinary oncological specialists have to cooperate closely to provide the best care for these patients. For the resection of brain metastasis several studies reported a considerable risk of new postoperative paresis. Pre- and perioperative chemotherapy (Ctx) or radiotherapy (Rtx) alter vasculature and adjacent fiber tracts on the one hand, and many patients already present with paresis prior to surgery on the other hand. As such factors were repeatedly considered risk factors for perioperative complications, we designed this study to also identify risk factors for brain metastases resection. Between 2006 and 2011, we resected 206 brain metastases consecutively, 56 in eloquent motor areas and 150 in non-eloquent ones. We evaluated the influences of preoperative paresis, previous Rtx or Ctx as well as recursive partitioning analysis (RPA) class on postoperative outcome. In general, 8.7% of all patients postoperatively developed a new permanent paresis. In contrast to preoperative Ctx, previous Rtx as a single or combined treatment strategy was a significant risk factor for postoperative motor weakness. This risk was even increased in perirolandic and rolandic lesions. Our data show significantly increased risk of new deficits for patients assigned to RPA class 3. Even in non-eloquently located brain metastases the risk of new postoperative paresis has not to be underestimated. Despite the microsurgical approach, our cohort shows a high rate of unexpected residual tumors in postoperative MRI, which supports recent data on brain metastases’ infiltrative nature but might also be the result of our strict study protocol. Surgical resection is a safe treatment of brain metastases. However, preoperative Rtx and RPA score 3 have to be taken into account when surgical resection is considered

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

    African Journals Online (AJOL)

    of epidermal growth factor receptor (EGFR-TKIs) for patients with brain metastases (BM) from non- small-cell lung ... [9,10]. Many studies have shown the responses of. NSCLC patients with BM to EGFR-TKIs [11-14], but most of ... The ORR was defined as the percentage of ..... d), which permit unrestricted use, distribution,.

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    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

  8. Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases. A single centre study

    Energy Technology Data Exchange (ETDEWEB)

    Wiggenraad, R.; Verbeek-de Kanter, A.; Mast, M. [Radiotherapy Centre West, The Hague (Netherlands); Molenaar, R. [Diaconessenhuis, Leiden (Netherlands). Dept. of Neurology; Lycklama a Nijeholt, G. [Medical Centre Haagladen, The Hague (Netherlands). Dept. of Radiology; Vecht, C. [Medical Centre Haagladen, The Hague (Netherlands). Dept. of Neurology; Struikmans, H. [Radiotherapy Centre West, The Hague (Netherlands); Leiden Univ. Medical Centre (Netherlands). Dept. of Radiotherapy; Kal, H.B.

    2012-08-15

    Purpose: The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases > 3 cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases. Materials and methods: In two consecutive periods, 41 patients with 46 brain metastases received SRT with 1 fraction of 15 Gy, while 51 patients with 65 brain metastases received FSRT with 3 fractions of 8 Gy. We included patients with brain metastases with a planning target volume of > 13 cm{sup 3} or metastases in the brainstem. Results: The minimum follow-up of patients still alive was 22 months. Comparing 1 fraction of 15 Gy with 3 fractions of 8 Gy, the 1-year rates of freedom from any local progression (54% and 61%, p = 0.93) and pseudo progression (85% and 75%, p = 0.25) were not significantly different. Overall survival rates were also not different. Conclusion: The 1-year local progression and pseudo progression rates after 1 fraction of 15 Gy or 3 fractions of 8 Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary. (orig.)

  9. Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases. A single centre study

    International Nuclear Information System (INIS)

    Wiggenraad, R.; Verbeek-de Kanter, A.; Mast, M.; Molenaar, R.; Lycklama a Nijeholt, G.; Vecht, C.; Struikmans, H.; Leiden Univ. Medical Centre; Kal, H.B.

    2012-01-01

    Purpose: The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases > 3 cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases. Materials and methods: In two consecutive periods, 41 patients with 46 brain metastases received SRT with 1 fraction of 15 Gy, while 51 patients with 65 brain metastases received FSRT with 3 fractions of 8 Gy. We included patients with brain metastases with a planning target volume of > 13 cm 3 or metastases in the brainstem. Results: The minimum follow-up of patients still alive was 22 months. Comparing 1 fraction of 15 Gy with 3 fractions of 8 Gy, the 1-year rates of freedom from any local progression (54% and 61%, p = 0.93) and pseudo progression (85% and 75%, p = 0.25) were not significantly different. Overall survival rates were also not different. Conclusion: The 1-year local progression and pseudo progression rates after 1 fraction of 15 Gy or 3 fractions of 8 Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary. (orig.)

  10. A case of leptospirosis simulating colon cancer with liver metastases.

    Science.gov (United States)

    Granito, Alessandro; Ballardini, Giorgio; Fusconi, Marco; Volta, Umberto; Muratori, Paolo; Sambri, Vittorio; Battista, Giuseppe; Bianchi, Francesco-B

    2004-08-15

    We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; alpha-fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was reevaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospirosis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two mo, biochemical data, CT and colonoscopy were totally normal.

  11. A case of leptospirosis simulating colon cancer with liver metastases

    Science.gov (United States)

    Granito, Alessandro; Ballardini, Giorgio; Fusconi, Marco; Volta, Umberto; Muratori, Paolo; Sambri, Vittorio; Battista, Giuseppe; Bianchi, Francesco B.

    2004-01-01

    We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; α - fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was revaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospirosis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two mo, biochemical data, CT and colonoscopy were totally normal. PMID:15285043

  12. Automatic detection and segmentation of brain metastases on multimodal MR images with a deep convolutional neural network.

    Science.gov (United States)

    Charron, Odelin; Lallement, Alex; Jarnet, Delphine; Noblet, Vincent; Clavier, Jean-Baptiste; Meyer, Philippe

    2018-04-01

    Stereotactic treatments are today the reference techniques for the irradiation of brain metastases in radiotherapy. The dose per fraction is very high, and delivered in small volumes (diameter convolutional neural network (DeepMedic) to detect and segment brain metastases on MRI. At first, we sought to adapt the network parameters to brain metastases. We then explored the single or combined use of different MRI modalities, by evaluating network performance in terms of detection and segmentation. We also studied the interest of increasing the database with virtual patients or of using an additional database in which the active parts of the metastases are separated from the necrotic parts. Our results indicated that a deep network approach is promising for the detection and the segmentation of brain metastases on multimodal MRI. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Iodine-125 brachytherapy as upfront and salvage treatment for brain metastases. A comparative analysis

    Energy Technology Data Exchange (ETDEWEB)

    Romagna, Alexander; Schwartz, Christoph; Tonn, Joerg-Christian; Kreth, Friedrich-Wilhelm [Ludwig-Maximilians-University, Department of Neurosurgery, Munich (Germany); Egensperger, Rupert [Ludwig-Maximilians-University, Center for Neuropathology and Prion Research, Munich (Germany); Watson, Juliana; Belka, Claus; Nachbichler, Silke Birgit [Ludwig-Maximilians-University, Department of Radiation-Oncology, Munich (Germany)

    2016-11-15

    Outcome and toxicity profiles of salvage stereotactic ablative radiation strategies for recurrent pre-irradiated brain metastases are poorly defined. This study compared risk-benefit profiles of upfront and salvage iodine-125 brachytherapy (SBT) for small brain metastases. As the applied SBT treatment algorithm required histologic proof of metastatic brain disease in all patients, we additionally aimed to elucidate the value of biopsy before SBT. Patients with small untreated (n = 20) or pre-irradiated (n =28) suspected metastases intended for upfront or salvage SBT, respectively, were consecutively included. Temporary iodine-125 implants were used (median reference dose: 50 Gy, median dose rate: 15 cGy/h). Cumulative biologically effective doses (BED) were calculated and used for risk assessment. Treatment toxicity was classified according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Upfront SBT was initiated in 20 patients and salvage SBT in 23. In 5 patients, salvage SBT was withheld because of proven radiation-induced lesions. Treatment groups exhibited similar epidemiologic data except for tumor size (which was slightly smaller in the salvage group). One-year local/distant tumor control rates after upfront and salvage SBT were similar (94 %/65 % vs. 87 %/57 %, p = 0.45, respectively). Grade I/II toxicity was suffered by 2 patients after salvage SBT (cumulative BED: 192.1 Gy{sub 3} and 249.6 Gy{sub 3}). No toxicity-related risk factors were identified. SBT combines diagnostic yield with effective treatment in selected patients. The low toxicity rate in the salvage group points to protective radiobiologic characteristics of continuous low-dose rate irradiation. Upfront and salvage SBT are similarly effective and safe. Histologic reevaluation should be reconsidered after previous radiotherapy to avoid under- or overtreatment. (orig.) [German] Daten zu Risiko und Effizienz ablativer

  14. Detection of occult bone metastases of lung cancer with fluorine-18 fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Ramdave, Shankar; Berlangieri, Salvatore U.

    2004-01-01

    Accurate staging of cancer has a critical role in optimal patient management. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastases in patients with non-small cell lung cancer. Although Tc-99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X-rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans Copyright (2004) Blackwell Publishing Asia Pty Ltd

  15. Ultrasound imaging of flow patterns in liver metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael; Solvig, Jan

    2004-01-01

    BACKGROUND: The ability of colour Doppler, power Doppler and echo-enhanced Doppler imaging to detect the blood flow in liver metastases from colorectal cancer was investigated. An evaluation was then made to determine whether the flow pattern could be used as an indication of disease elsewhere....... METHODS: Forty-two patients with hepatic metastases from colorectal cancer were examined, 8 of whom had local recurrence of their colorectal cancer. Seventy-seven liver metastases were evaluated with colour Doppler and power Doppler, and the presence or absence of a Doppler signal in the halo or centre...... was noted. Forty-three of these metastases were further examined after contrast media echo-enhancement. RESULTS: Signals from the peripheral halo were detected by colour Doppler imaging in 34% of the metastases, and in 77% by power Doppler (P power Doppler...

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

    International Nuclear Information System (INIS)

    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

  17. Outcome After Radiosurgery for Brain Metastases in Patients With Low Karnofsky Performance Scale (KPS) Scores

    International Nuclear Information System (INIS)

    Chernov, Mikhail F.; Nakaya, Kotaro; Izawa, Masahiro; Hayashi, Motohiro; Usuba, Yuki; Kato, Koichi; Muragaki, Yoshihiro; Iseki, Hiroshi; Hori, Tomokatsu; Takakura, Kintomo

    2007-01-01

    Purpose: The objective of this retrospective study was evaluation of the outcome after stereotactic radiosurgery (SRS) in patients with intracranial metastases and poor performance status. Methods and Materials: Forty consecutive patients with metastatic brain tumors and Karnofsky performance scale (KPS) scores ≤50 (mean, 43 ± 8; median, 40) treated with SRS were analyzed. Poor performance status was caused by presence of intracranial metastases in 28 cases (70%) and resulted from uncontrolled extracerebral disease in 12 (30%). Results: Survival after SRS varied from 3 days to 11.5 months (mean, 3.8 ± 2.9 months; median, 3.3 months). Survival probability constituted 0.50 ± 0.07 at 3 months and 0.20 ± 0.05 at 6 months posttreatment. Cause of low KPS score (p = 0.0173) and presence of distant metastases beside the brain (p = 0.0308) showed statistically significant associations with overall survival in multivariate Cox proportional hazards regression analysis. Median survival was 6.0 months if low KPS score was caused by cerebral disease and distant metastases in regions beyond the brain were absent, 3.3 months if low KPS score was caused by cerebral disease and distant metastases in regions beyond the brain were present, and 1.0 month if poor performance status resulted from extracerebral disease. Conclusions: Identification of the cause of low KPS score (cerebral vs. extracerebral) in patients with metastatic brain tumor(s) may be important for prediction of the outcome after radiosurgical treatment. If poor patient performance status without surgical indications is caused by intracranial tumor(s), SRS may be a reasonable treatment option

  18. A concise review of the efficacy of stereotactic radiosurgery in the management of melanoma and renal cell carcinoma brain metastases

    Directory of Open Access Journals (Sweden)

    Hanson Peter W

    2012-08-01

    Full Text Available Abstract Melanoma and renal cell carcinoma have a well-documented tendency to develop metastases to the brain. Treating these lesions has traditionally been problematic, because chemotherapy has difficulty crossing the blood brain barrier and whole brain radiation therapy (WBRT is a relatively ineffective treatment against these radioresistant tumor histologies. In recent years, stereotactic radiosurgery (SRS has emerged as an effective and minimally-invasive treatment modality for irradiating either single or multiple intracranial structures in one clinical treatment setting. For this reason, we conducted a review of modern literature analyzing the efficacy of SRS in the management of patients with melanoma and renal cell carcinoma brain metastases. In our analysis we found SRS to be a safe, effective and attractive treatment modality for managing radioresistant brain metastases and highlighted the need for randomized trials comparing WBRT alone vs. SRS alone vs. WBRT plus SRS in treating patients with radioresistant brain metastases.

  19. Whole brain radiotherapy after local treatment of brain metastases in melanoma patients - a randomised phase III trial

    International Nuclear Information System (INIS)

    Fogarty, Gerald; Shivalingam, Brindha; Dhillon, Haryana; Thompson, John F; Morton, Rachael L; Vardy, Janette; Nowak, Anna K; Mandel, Catherine; Forder, Peta M; Hong, Angela; Hruby, George; Burmeister, Bryan

    2011-01-01

    Cerebral metastases are a common cause of death in patients with melanoma. Systemic drug treatment of these metastases is rarely effective, and where possible surgical resection and/or stereotactic radiosurgery (SRS) are the preferred treatment options. Treatment with adjuvant whole brain radiotherapy (WBRT) following neurosurgery and/or SRS is controversial. Proponents of WBRT report prolongation of intracranial control with reduced neurological events and better palliation. Opponents state melanoma is radioresistant; that WBRT yields no survival benefit and may impair neurocognitive function. These opinions are based largely on studies in other tumour types in which assessment of neurocognitive function has been incomplete. This trial is an international, prospective multi-centre, open-label, phase III randomised controlled trial comparing WBRT to observation following local treatment of intracranial melanoma metastases with surgery and/or SRS. Patients aged 18 years or older with 1-3 brain metastases excised and/or stereotactically irradiated and an ECOG status of 0-2 are eligible. Patients with leptomeningeal disease, or who have had previous WBRT or localised treatment for brain metastases are ineligible. WBRT prescription is at least 30 Gy in 10 fractions commenced within 8 weeks of surgery and/or SRS. Randomisation is stratified by the number of cerebral metastases, presence or absence of extracranial disease, treatment centre, sex, radiotherapy dose and patient age. The primary endpoint is the proportion of patients with distant intracranial failure as determined by MRI assessment at 12 months. Secondary end points include: survival, quality of life, performance status and neurocognitive function. Accrual to previous trials for patients with brain metastases has been difficult, mainly due to referral bias for or against WBRT. This trial should provide the evidence that is currently lacking in treatment decision-making for patients with melanoma brain

  20. Limphographic characteristics of the metastases in cancer of the urinary bladder

    International Nuclear Information System (INIS)

    Baldzhijski, A.; Panchev, V.; Simeonov, I.

    1984-01-01

    A total of 887 pedal lymphographies have been performed, 178 of them (173 men and 5 women) in a search for metastases of bladder cancer. Lymphography showed positive result for metastases in 110 patients (61,71 per cent); in 58 patients it was evaluated as negative for metastases (32,58 per cent) and in 9 (5,63 per cent) gave equivocal result. Most frequently affected were the iliac lywph groups, thf first barrier - 100 per cent involvement in proven metastases. Next in incidence of involvement (second barrier) were the paraortal lymphgroups - 55,45 per cent. Te external iliac inguinal groups were the ones most seldom affected

  1. Results of radiotherapy for brain metastases in old-aged patients

    International Nuclear Information System (INIS)

    Nieder, C.; Niewald, M.; Schnabel, K.

    1995-01-01

    To evaluate which patients older tahn 70 years will benefit by radiotherapy for their brain metastases the data of 35 patients in this age-group who were treated between 1983 and 1994 were retrospectivley analyzed. All patients were previously untreated and received a whole-brain irradiation and concomitantly corticosteroids. The median total dose was 30 Gy (fractionation: 10 times 3 Gy in 2 weeks). Six patients each received lower or higher total doses with 50.4 Gy at maximum. Six patients failed to complete their prescribed treatment (17%). The median survival of all patients who completed their radiotherapy course was 67 days only. Patients with extracerebral metastases had a median survival of 31 days. Survival was not dependent on total dose of radiotherapy. In 56% of all cases the general condition of the patients improved or remained stable at a high level. Karnofsky-performance status was the most important prognostic factor. Advanced age is an unfavourable prognostic factor. Only patients in good general condition without extracerebral metastases had survival times which justify radiotherapy for their brain metastases. (orig./MG) [de

  2. Risk factors and characteristics of prostate cancer bone metastases

    Directory of Open Access Journals (Sweden)

    Jun-ming LIN

    2017-10-01

    Full Text Available Objective To analyze the risk factors and characteristics of bone metastases in patients with prostate cancer. Methods Patients who were diagnosed as prostate cancer by biopsy and histopathologic analysis between June 2006 and June 2016 were included in this study. The clinical data of the patients were reviewed, and the demographic data, laboratory examination results and Gleason score were recorded. The correlations between clinical factors and bone metastasis were analyzed, and the risk factors of bone metastasis were identified. Results A total of 585 patients were recruited in this study, including 228 with bone metastasis and 357 without bone metastasis. Of the patients with bone metastasis, the incidence of pelvic metastasis was the highest, accounting for 81.58%, followed by spin (63.16% and rib (58.33%, and the incidence of clavicle metastasis was the lowest (14.47%. Logistic regression analysis showed that age 85.5U/L, prostate-specific antigen >79.88μg/L and Gleason score >7.5 were the risk factors of bone metastasis in prostate cancer. ROC curve analysis showed that the sensitivity of diagnosing bone metastasis was 56.1%, 66.7%, 68.4% and 56.1%, and the specificity was 56.6%, 81.8%, 70.0% and 65.3%, respectively for above 4 factors. Conclusions The most common site of bone metastasis in patients with prostate cancer is pelvis. Patients' age, concentrations of plasma ALP and PSA, and Gleason score are the risk factors for bone metastasis in patients with prostate cancer. DOI: 10.11855/j.issn.0577-7402.2017.08.09

  3. Remission of Unresectable Lung Metastases from Rectal Cancer After Herbal Medicine Treatment: A Case Report.

    Science.gov (United States)

    Kim, Kyungsuk; Lee, Sanghun

    2016-01-01

    Lung metastasis is frequent in rectal cancer patients and has a poor prognosis, with an expected three-year survival rate of about 10%. Though western medicine has made great strides in the curative resection of liver metastases, resection of lung metastases has lagged far behind. Many preclinical studies have suggested that herbal treatments block metastasis, but few clinical studies have addressed this topic. We present the case of a 57-year-old Asian male with lung metastases from rectal cancer. He first underwent resection of the primary lesion (stage IIA, T3N0M0) and six cycles of adjuvant chemotherapy. Unfortunately, lung metastases were confirmed about one year later. Palliative chemotherapy was begun, but his disease continued to progress after three cycles and chemotherapy was halted. The patient was exclusively treated with herbal medicine-standardized allergen-removed Rhus verniciflua stokes extract combined with Dokhwaljihwang-tang (Sasang constitutional medicine in Korea). After seven weeks of herbal medicine treatment, the lung metastases were markedly improved. Regression of lung metastases has continued; also, the patient's rectal cancer has not returned. He has been receiving herbal medicine for over two years and very few side effects have been observed. We suggest that the herbal regimen used in our patient is a promising candidate for the treatment of lung metastases secondary to rectal cancer, and we hope that this case stimulates further investigation into the efficacy of herbal treatments for metastatic colorectal cancer patients. Copyright © 2016. Published by Elsevier Inc.

  4. 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...

  5. Assessment of brain metastases by means of dynamic susceptibility contrast enhanced MRI

    International Nuclear Information System (INIS)

    Knopp, M.; Wenz, F.; Debus, J.; Hentrich, H.R.

    2002-01-01

    Full text: To assess if pre therapeutic measurements of regional cerebral blood flow (rCBF) and volume (rCVB) are able to predict the response of brain metastases to radiation therapy and to assess the influence of radiosurgery on rCBF and rCBV on brain metastases and normal surrounding tissue. We examined 25 patients with brain metastases prior to high dose radiosurgery with conventional T1 and T2 weighted MRI and dynamic susceptibility contrast enhanced MRI (DSC MRI). For DSC MRI 55 T2*w GE images of two sections were acquired after bolus administration of 0.1 mmol/kg gadoteridol (ProHance) for the simultaneous measurement of brain feeding arteries and brain tissue. This allowed an absolute quantification of rCBF and rCBV. Follow-up examinations were performed 6 weeks and 3 months after radiotherapy and the acquired perfusion data were related to a 3 point scale of treatment outcome. Radiosurgery was performed by a linear accelerator with a 80% isodose of 18-20 Gv. For treatment planning the heads of the patients were immobilized by a cask mask to avoid head movement. DSC MRI was able to assess perfusion data in all patients. Higher pre therapeutic rCBV seems to predict a poor treatment outcome. After radiosurgery patients with tumor remission and stable disease presented a decrease of rCBV over time regardless of temporary tumor volume increase. Patients with tumor progression at the 3 month followup presented an increase of rCBV. Effects on normal surrounding tissue could not be observed. DSC MRI using Gadoteridol allows the non-invasive assessment of rCBV and rCBF of brain metastases and its changes due to radiosurgery. The method may also be able to predict treatment outcome. Furthermore radiofrequency effects on surrounding unaffected tissue can be monitored. Copyright (2002) Blackwell Science Pty Ltd

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

    Science.gov (United States)

    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

  7. Brain metastases of solid tumour. Treatment distribution and analysis of survival in the period 1/01/2004 to 31/12/2008

    International Nuclear Information System (INIS)

    Xavier, F.; Rodriguez, R.; Lima, R.; Rios, A.; Mara, C.

    2010-01-01

    Objective: To retrospectively analyze the characteristics, treatments and survival analysis in patients with solid tumors with brain metastases (E IV) assisted in Unit Neuro-Oncology over a period of five years. Patients and methods: The records of patients (pts) with diagnosis of brain metastases from solid tumors assisted in Neuro-Oncology Unit, from 1/01/2004 and 31/12/2008. Results: 51 new patients carriers of brain metastases were treated with solid tumors. The median age at diagnosis was 57 years, ranging from 30 to 75. They corresponded to the male 37 and female 14 ratio 2.5 / 1. The majority was presented as metastases 31/51. The location was in the supratentorial region in 27 cases, posterior fossa in 11 and 13 were supra and infratentorial. In only 5 patients cranial MRI was performed in only one case and it changed the therapeutical strategy. In 35 patients he corresponded to the lung primary tumor (CBP), following cancer renal (5/51). Within the CBP, the most common histologic subtypes were to large cells and adenocarcinomas, 11 and 10, respectively. In 32 patients were not found dissemination elsewhere. Surgery + RT was performed in 30 cases, in 11 exclusive RT, exclusive surgery in 4 and 3 patients symptomatic treatment. In 39 cases did not Systemic treatment diagnosis. When a progression was only diagnosed It could make systemic treatment 5 pts. The median survival was 15.4 weeks (1-301 weeks). Conclusions: Lung cancer is the most common source of metastases brain, with a poor survival. The results of other characteristics patients, systemic treatments performed and survival according to the treatments performed will be presented during the congresss

  8. [Liver metastases from colon and rectal cancer in terms of differences in their clinical parameters].

    Science.gov (United States)

    Liška, V; Emingr, M; Skála, M; Pálek, R; Troup, O; Novák, P; Vyčítal, O; Skalický, T; Třeška, V

    2016-02-01

    From the clinical point of view, rectal cancer and colon cancer are clearly different nosological units in their progress and treatment. The aim of this study was to analyse and clarify the differences between the behaviour of liver metastases from colon and rectal cancer. The study of these factors is important for determining an accurate prognosis and indication of the most effective surgical therapy and oncologic treatment of colon and rectal cancer as a systemic disease. 223 patients with metastatic disease of colorectal carcinoma operated at the Department of Surgery, University Hospital in Pilsen between January 1, 2006 and January 31, 2012 were included in our study. The group of patients comprised 145 men (65%) and 117 women (35%). 275 operations were performed. Resection was done in 177 patients and radiofrequency ablation (RFA) in the total of 98 cases. Our sample was divided into 3 categories according to the location of the primary tumor to C (colon), comprising 58 patients, S (c. sigmoideum) in 61 patients, and R (rectum), comprising 101 patients. Significance analysis of the studied factors (age, gender, staging [TNM classification], grading, presence of mucinous carcinoma, type of operation) was performed using ANOVA test. Overall survival (OS), disease-free interval (DFI) or no evidence of disease (NED) were estimated using Kaplan-Meier curves, which were compared with the log-rank and Wilcoxon tests. As regards the comparison of primary origin of colorectal metastases in liver regardless of their treatment (resection and RFA), our study indicated that rectal liver metastases showed a significantly earlier recurrence than colon liver metastases (shorter NED/DFI). Among other factors, a locally advanced finding, further R2 resection of liver metastases and positivity of lymph node metastases were statistically significant for the prognosis of an early recurrence of the primary colon and sigmoid tumor. Furthermore, we proved that in patients with

  9. Biological Differences Between Prostate Cancer Cells that Metastasize to Bone Versus Soft Tissue Sites

    National Research Council Canada - National Science Library

    Pienta, Kenneth J

    2004-01-01

    .... Comparisons were made between patients as well as within the same patient. No consistent differences were found between bone and soft tissue sites that could explain the predilection of prostate cancer cells to metastasize to bone...

  10. Development of a Modelling to Correlate Site and Diameter of Brain Metastases with Hippocampal Sparing Using Volumetric Modulated Arc Therapy

    Directory of Open Access Journals (Sweden)

    Silvia Chiesa

    2013-01-01

    Full Text Available Purpose. To correlate site and diameter of brain metastases with hippocampal sparing in patients treated by RapidArc (RA technique on whole brain with simultaneously integrated boost (SIB. Methods and Materials. An RA plan was calculated for brain metastases of 1-2-3 cm of diameter. The whole brain dose was 32.25 Gy (15 fractions, and SIB doses to brain metastases were 63 Gy (2 and 3 cm or 70.8 Gy (1 cm. Plans were optimized and evaluated for conformity, target coverage, prescription isodose to target volume, homogeneity index, and hippocampal sparing. Results. Fifteen brain lesions and RA plan were generated. Hippocampal volume was 4.09 cm3, and hippocampal avoidance volume was 17.50 cm3. Related to site of metastases, the mean hippocampal dose was 9.68 Gy2 for occipital lobe, 10.56 Gy2 for frontal lobe, 10.56 Gy2 for parietal lobe, 10.94 Gy2 for deep brain structures, and 40.44 Gy2 for temporal lobe. The mean hippocampal dose was 9.45 Gy2, 10.15 Gy2, and 11.70 Gy2 for diameter’s metastases of 1.2 and 3 cm, respectively, excluding results relative to temporal brain lesions. Conclusions. Location more than size of metastases can adversely influence the hippocampus sparing. Further investigation is necessary to meet definitive considerations.

  11. Optimization of brain metastases radiotherapy with TomoHDA

    Energy Technology Data Exchange (ETDEWEB)

    Yartsev, Slav, E-mail: slav.yartsev@lhsc.on.ca; Bauman, Glenn

    2017-04-01

    An upgrade of the helical tomotherapy technology by introducing variable fan-field width (dynamic jaws) reduced the penumbra in superior-inferior direction for the target. Possible implementation of this upgrade even for the cases of the targets with different dose prescriptions is proposed. An example of brain metastasis in proximity to the optical apparatus in need of the whole brain irradiation of 30 Gy and higher dose to the lesion is considered.

  12. Survival in patients with brain metastases treated with radiotherapy holoencefalica at the National Institute of Cancerology

    International Nuclear Information System (INIS)

    Ospino, Rosalba; Cendales, Ricardo; Tria, Jaime

    2009-01-01

    Objective: To describe the overall survival among patients with brain metastases treated with whole brain radiation therapy at the Instituto Nacional de Cancerologia (INC) during 2004-2006. Methods: A survival study was conducted. All patients with brain metastases treated with whole brain radiotherapy were included. Frequencies, central tendency, and dispersion measures were used to describe discrete and continuous variables. Survival analysis was performed by the Kaplan-Meyer method. Results: 109 patients were included and the vital status was updated in 85 patients (80%). The median follow-up time was 2.76 months. 78 deaths were observed; the median survival time was 5.2 months and the cumulated one-year overall survival 25.5%. Karnofsky index, extra-cranial metastases, type of lesion, and recursive partitioning analysis (RPA) were significant prognostic factors. The overall median survival for recursive partitioning analysis class I was 7.2 months; class II 6.9 months; class III 1.8 months. Conclusion: Overall survival INC are similar than previous international series for RPA class I and III, while it was better in RPA class II.

  13. Post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Su; Kim, Kyu Bo; Chie, Eui Kyu; Kim, Yoon Jun; Yoon, Jung Hwan; Lee, Hyo Suk; Ha, Sung W. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-03-15

    To evaluate the incidence and risk factors of post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma (HCC). Medical records of 81 patients who have been diagnosed of brain metastases from HCC and underwent surgery, radiosurgery and/or whole brain radiotherapy (WBRT) between January 2000 and December 2013 were retrospectively reviewed. Intracranial hemorrhage was present in 64 patients (79%) at the time of diagnosis. Median value of alpha-fetoprotein (AFP) level was 1,700 ng/mL. The Eastern Cooperative Oncology Group (ECOG) performance status for 20 patients was greater than 2. Fifty-seven patients underwent WBRT and the others were treated with surgery and/or radiosurgery without WBRT. During follow-up, 12 events of intracranial hemorrhage after treatment were identified. Three-month post-treatment hemorrhage rate was 16.1%. Multivariate analyses revealed that ECOG performance status, AFP, and WBRT were associated with post-treatment hemorrhage (p = 0.013, 0.013, and 0.003, respectively). Kaplan-Meier analysis showed that 3-month post-treatment hemorrhage rate of new lesion was higher in patients treated without WBRT, although statistical significance was not reached. (18.6% vs. 4.6%; p = 0.104). Ten of 12 patients with post-treatment hemorrhage died with neurologic cause. WBRT should be considered to prevent post-treatment hemorrhage in the treatment of brain metastases from HCC.

  14. Primary pleuropulmonary synovial sarcoma with brain metastases in a paediatric patient: an unusual presentation.

    Science.gov (United States)

    Chirmade, Pushpak Chandrakant; Parikh, Sonia; Anand, Asha; Panchal, Harsha; Patel, Apurva; Shah, Sandip

    2017-01-01

    Primary lung neoplasms are rare in children. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumour. Synovial sarcoma (SS) accounts for approximately 1% of all childhood malignancies. In absolute terms, the SS of the lungs and pleura are extremely rare and pose a diagnostic difficulty. Soft tissue sarcomas usually have a high potential for metastases, however, metastasis to the brain is rare, even in widely disseminated disease, and it has been described only in 3 case reports previously. Primary pleuropulmonary SS with brain metastases is even rarer. Here we present a case of an 11-year-old boy who presented with respiratory complaints, viz. fever and cough for 20 days. Initial impression was lung abscess, however, on histopathological, immunohistochemical and molecular study, the disorder was diagnosed as synovial sarcoma. After a week from the first consult, the child developed neurological symptoms, viz., an episode of convulsion and gradually worsening power of the lower limb. Computed tomography scan and Magnetic Resonance Spectroscopy was suggestive of brain metastases. Given the rarity of primary lung neoplasms in children, clinical detection remains a challenge. Delayed diagnoses are common as respiratory symptoms may be attributed to inflammatory or infective processes. Primary pleuropulmonary synovial sarcoma is a rare tumour and it is not known to commonly metastasise to the brain. Though rare, primary pleuropulmonary SS should be considered an important differential among peadiatric primary lung neoplasms due to its potential for curability if detected early, and more aggressive metastatic pattern, e.g. brain metastases making early detection imperative.

  15. Intensity-modulated Radiosurgery for patients with brain metastases: a mature outcomes analysis.

    Science.gov (United States)

    Wang, Samuel J; Choi, Mehee; Fuller, Clifton D; Salter, Bill J; Fuss, Martin

    2007-06-01

    The purpose of this study was to evaluate the outcomes of patients with brain metastases treated by tomotherapeutic Intensity-modulated Radiosurgery (IMRS). Using retrospective chart review, we analyzed the outcomes of 78 patients (age 33-83 years, median 57 years) who underwent 111 sessions of IMRS (1 to 7 sessions per patient, median 1) for brain metastases (1 to 4 targets per IMRS session, median 1) treated between 2000 and 2005 using a serial tomotherapeutic intensity-modulated radiotherapy treatment (IMRT) planning and delivery system (Peacock, Nomos Corp., Cranberry Township, PA). Treatment planning was performed using an inverse treatment planning optimization algorithm that was optimized for IMRS. A median prescription dose of 15 Gy in combination with WBI, and median 20 Gy for IMRS alone was delivered using 2-4 couch angles over 4-24 rotational arcs. Overall survival was calculated using Kaplan-Meier analysis. To determine the effects of prognostic variables on survival, univariate and multivariate analyses using proportional hazards were performed to assess the effects of age, tumor size, the combination with whole brain irradiation, presence of multiple brain metastases, and presence of extracranial disease. The median overall survival was 6.5 months (95% CI, 5.5-7.9). One- and two-year survival rates were 24% and 10%. In multivariate analyses, age greater than 60 years was the only statistically significant variable that affected survival (hazard rate 1.29, p=0.049). We conclude that tomotherapeutic IMRS is safe and effective to treat patients with brain metastases.

  16. Foe or friend? Janus-faces of the neurovascular unit in the formation of brain metastases.

    Science.gov (United States)

    Wilhelm, Imola; Fazakas, Csilla; Molnár, Kinga; Végh, Attila G; Haskó, János; Krizbai, István A

    2018-04-01

    Despite the potential obstacle represented by the blood-brain barrier for extravasating malignant cells, metastases are more frequent than primary tumors in the central nervous system. Not only tightly interconnected endothelial cells can hinder metastasis formation, other cells of the brain microenvironment (like astrocytes and microglia) can also be very hostile, destroying the large majority of metastatic cells. However, malignant cells that are able to overcome these harmful mechanisms may benefit from the shielding and even support provided by cerebral endothelial cells, astrocytes and microglia, rendering the brain a sanctuary site against anti-tumor strategies. Thus, cells of the neurovascular unit have a Janus-faced attitude towards brain metastatic cells, being both destructive and protective. In this review, we present the main mechanisms of brain metastasis formation, including those involved in extravasation through the brain vasculature and survival in the cerebral environment.

  17. Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS

    Energy Technology Data Exchange (ETDEWEB)

    Shultz, David B.; Modlin, Leslie A.; Jayachandran, Priya; Von Eyben, Rie; Gibbs, Iris C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Choi, Clara Y.H. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Department of Radiation Oncology, Santa Clara Valley Medical Center, San Jose, California (United States); Chang, Steven D.; Harsh, Griffith R.; Li, Gordon; Adler, John R. [Department of Neurosurgery, Stanford University School of Medicine, Stanford, California (United States); Hancock, Steven L. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Soltys, Scott G., E-mail: sgsoltys@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2015-08-01

    Purpose: To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS). Patients and Methods: We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS. Results: Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites. Conclusion: Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.

  18. The role of stereotactic radiation therapy and whole-brain radiotherapy in the treatment of multiple brain metastases

    International Nuclear Information System (INIS)

    Chen Xiujun; Xiao Jianping; Li Xiangpan; Jiang Xuesong; Zhang Ye; Xu Yingjie; Dai Jianrong; Li Yexiong

    2012-01-01

    Objective: To summarize the results of stereotactic radiation therapy (SRT) with or without whole-brain radiotherapy (WBRT) in the treatment of multiple brain metastasis. Methods: From May 1995 to April 2010, totally 98 newly diagnosed multiple (2 - 13 lesions) brain metastases patients were treated in our centre. Forty-four patients were treated with SRT alone and 54 with SRT + WBRT. Dose fractionation schemes were 15 -26 Gy in 1 fraction or 24.0 -52.5 Gy in 2 - 15 fractions with 3.5 - 12.0 Gy per fraction, depending on the tumor volume, location, and history of prior irradiation. Kaplan-Meier and Cox proportional hazards regression analyses were used for survival analysis. The median age of the whole group was 55 years. The survival time was calculated from the date of radiation treatment to the day of death by any cause. Results: The median follow-up time for the whole group was 12 months, and the follow-up rate was 100%. The median overall survival time was 13.5 months for the whole group, there was no difference between SRT alone group and SRT + WBRT group (13.0 months vs. 13.5 months, χ 2 =0.31, P =0.578). The Karnofsky Performance Score (KPS) at the time of treatment (χ 2 =6.25, P =0.012), the interval between the diagnosis of the primary tumor and brain metastases (χ 2 =7.34, P =0.025) and the status of extracranial metastases (χ 2 =4.20, P =0.040) were independent prognosis factors for survival in multivariate analyses. Conclusions: Stereotactic radiation therapy is an effective and alternative treatment choice for multiple brain metastases. (authors)

  19. Rectal Metastases from Squamous Cell Carcinoma: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    S. Cedrés

    2012-01-01

    Full Text Available Non-small-cell lung cancer (NSCLC represents 85% of lung cancer. The most frequent sites of distant metastasis are the liver, adrenal glands, bones and brain. Gastrointestinal metastases are uncommon and rectal metastases are extremely rare. Here we report a case of squamous cell carcinoma of the lung with rectal metastases.

  20. Stereotactic radiosurgery in the palliative treatment of brain metastases

    International Nuclear Information System (INIS)

    Faria, Sergio L.; Souhami, Luis; Bahary, Jean-Paul; Clark, Brenda; Adamson, Nelson; Podgorsak, Ervin B.; Caron, Jean-Louis; Villemure, Jean-Guy; Olivier, Andre

    1995-01-01

    Between October, 1988 and November, 1993, 57 patients with metastatic brain disease underwent stereotactic radiosurgery at McGill University, canada. Four patients were excluded from this analysis leaving a total of 53 evaluable patients (with 57 lesions). Radiosurgery was performed with the dynamic rotation technique which uses an isocentric, 10 MV, linear accelerator. A median dose of 1,800 c Gy was given in a single session. In 89% of the cases radiosurgery was used after failure to conventional brain radiotherapy. With a median follow-up of 6 months, the response rate was 65% . Treatments were well tolerated and only 4 patients (7%) developed late complications related to the therapy, with one patient requiring a surgical resection of an area of radionecrose. Radiosurgery appears to be and effective and safe treatment for selected patients with metastatic brain disease, recurrent post-conventional radiotherapy. Its value as a single treatment modality for patients with isolated brain metastasis is now being studied in prospective trials. (author). 29 refs., 4 figs., 4 tabs

  1. Brain metastases from thyroid carcinoma : studies of cases

    International Nuclear Information System (INIS)

    Perumal, N.S.; Kotze, T.; Vangu, M.D.T.H.W.

    2004-01-01

    Full text: Introduction: Because brain metastasis from well differentiated thyroid carcinoma is rare, management of patients presenting with this condition lacks consensus. A recent review of the literature found 17 reports of 75 cases from 1966-2001 in which 28 metastasis were from the brain, 5 from the spinal cord, 2 to both brain and spinal cord, We report our 5 cases with a focus on the last patient. Clinical presentation: A 66-year-old female treated by us for the past 10 years for papillary carcinoma of the thyroid with metastasis to bone. She presented in July 2003 with sudden onset of seizure. A non contrast CT scan demonstrated a solitary lesion in the right anterior high parietal region with a possible second lesion. Intervention: She underwent right frontal craniotomy to expose superior sagittal sinus. An inter-hemispheric approach demonstrated a tumor in the supra-meningeal gyrus that was attached to the calloso-meningeal artery. The histopathology of the surgical specimen confirmed a follicular variant of papillary carcinoma of the thyroid. She then received 11100 MBq 1-131 irradiation, Conclusion: the best therapeutic option for brain metastasis seems to be surgical resection with or without post operative Irradiation with 1-131. Central nervous system metastasis should always be investigated and treated aggressively to improve patients' long term outcome. (author)

  2. Detection of occult bone metastases of lung cancer with Fluorine-18 fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Foo, S.S.; Ramdave, S.; Berlangieri, S.U.; Scott, A.M.

    2004-01-01

    Accurate staging of cancer has a critical role in optimal patient management. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastasesin patients with non-small cell lung cancer. Although Tc-99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X-rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans. Copyright (2004) Blackwell Science Pty Ltd

  3. Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

    International Nuclear Information System (INIS)

    Ahmed, Kamran A.; Fulp, William J.; Berglund, Anders E.; Hoffe, Sarah E.; Dilling, Thomas J.; Eschrich, Steven A.; Shridhar, Ravi; Torres-Roca, Javier F.

    2015-01-01

    Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger

  4. Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Kamran A. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Fulp, William J.; Berglund, Anders E. [Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Hoffe, Sarah E.; Dilling, Thomas J. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Eschrich, Steven A. [Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Shridhar, Ravi [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States)

    2015-07-15

    Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger

  5. 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.

  6. The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer

    International Nuclear Information System (INIS)

    Brockton, Nigel T.; Gill, Stephanie J.; Laborge, Stephanie L.; Paterson, Alexander H. G.; Cook, Linda S.; Vogel, Hans J.; Shemanko, Carrie S.; Hanley, David A.; Magliocco, Anthony M.; Friedenreich, Christine M.

    2015-01-01

    Bone is the most common site of breast cancer distant metastasis, affecting 50–70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the

  7. The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer.

    Science.gov (United States)

    Brockton, Nigel T; Gill, Stephanie J; Laborge, Stephanie L; Paterson, Alexander H G; Cook, Linda S; Vogel, Hans J; Shemanko, Carrie S; Hanley, David A; Magliocco, Anthony M; Friedenreich, Christine M

    2015-07-10

    Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the

  8. Reliability of the Bony Anatomy in Image-Guided Stereotactic Radiotherapy of Brain Metastases

    International Nuclear Information System (INIS)

    Guckenberger, Matthias; Baier, Kurt; Guenther, Iris; Richter, Anne; Wilbert, Juergen; Sauer, Otto; Vordermark, Dirk; Flentje, Michael

    2007-01-01

    Purpose: To evaluate whether the position of brain metastases remains stable between planning and treatment in cranial stereotactic radiotherapy (SRT). Methods and Materials: Eighteen patients with 20 brain metastases were treated with single-fraction (17 lesions) or hypofractionated (3 lesions) image-guided SRT. Median time interval between planning and treatment was 8 days. Before treatment a cone-beam CT (CBCT) and a conventional CT after application of i.v. contrast were acquired. Setup errors using automatic bone registration (CBCT) and manual soft-tissue registration of the brain metastases (conventional CT) were compared. Results: Tumor size was not significantly different between planning and treatment. The three-dimensional setup error (mean ± SD) was 4.0 ± 2.1 mm and 3.5 ± 2.2 mm according to the bony anatomy and the lesion itself, respectively. A highly significant correlation between automatic bone match and soft-tissue registration was seen in all three directions (r ≥ 0.88). The three-dimensional distance between the isocenter according to bone match and soft-tissue registration was 1.7 ± 0.7 mm, maximum 2.8 mm. Treatment of intracranial pressure with steroids did not influence the position of the lesion relative to the bony anatomy. Conclusion: With a time interval of approximately 1 week between planning and treatment, the bony anatomy of the skull proved to be an excellent surrogate for the target position in image-guided SRT

  9. Pattern of Colon Cancer Lymph Node Metastases in Patients Undergoing Central Mesocolic Lymph Node Excision

    DEFF Research Database (Denmark)

    Bertelsen, Claus A; Kirkegaard-Klitbo, Anders; Nielsen, Mingyuan

    2016-01-01

    BACKGROUND: Extended mesocolic lymph node dissection in colon cancer surgery seems to improve oncological outcome. A possible reason might be related to metastases in the central mesocolic lymph nodes. OBJECTIVE: The purpose of this study was to describe the pattern of mesocolic lymph node...... metastases, particularly in central lymph nodes, and the risk of skip, aberrant, and gastrocolic ligament metastases as the argument for performing extended lymph node dissection. DATA SOURCES: EMBASE and PubMed were searched using the terms colon or colorectal with sentinel node, lymph node mapping, or skip...... node; lymph node resection colon; and complete or total and mesocolic excision. STUDY SELECTION: Studies describing the risk of metastases in central, skip, aberrant, and gastrocolic ligament lymph node metastases from colon adenocarcinomas in 10 or more patients were included. No languages were...

  10. Identification of a seasonal pattern to brain metastases

    Directory of Open Access Journals (Sweden)

    Sakellakis M

    2016-03-01

    Full Text Available Minas Sakellakis,1 Angelos Koutras,1 Maria Pittaka,2 Dimitrios Kardamakis,2 Melpomeni Kalofonou,1 Haralabos P Kalofonos,1 Despina Spyropoulou2 1Division of Oncology, Department of Medicine, 2Department of Radiation Oncology, University Hospital, Patras Medical School, Rion, Patras, GreeceWe have previously tested our hypothesis that there is a seasonality in the incidence of carcinomatous meningitis.1 Although further validation is needed in a larger cohort, we found that leptomeningeal metastasis occurred more often during warm months of the year which, in the case of Greece, is the period generally marked with the larger daytime length.1 Carcinomatous meningitis is closely related to brain metastasis, and a logical question is whether warm season is marked by a greater propensity also for brain metastasis.2 

  11. Effect of prophylactic hyperbaric oxygen treatment for radiation-induced brain injury after stereotactic radiosurgery of brain metastases

    International Nuclear Information System (INIS)

    Ohguri, Takayuki; Imada, Hajime; Kohshi, Kiyotaka; Kakeda, Shingo; Ohnari, Norihiro; Morioka, Tomoaki; Nakano, Keita; Konda, Nobuhide; Korogi, Yukunori

    2007-01-01

    Purpose: The purpose of the present study was to evaluate the prophylactic effect of hyperbaric oxygen (HBO) therapy for radiation-induced brain injury in patients with brain metastasis treated with stereotactic radiosurgery (SRS). Methods and Materials: The data of 78 patients presenting with 101 brain metastases treated with SRS between October 1994 and September 2003 were retrospectively analyzed. A total of 32 patients with 47 brain metastases were treated with prophylactic HBO (HBO group), which included all 21 patients who underwent subsequent or prior radiotherapy and 11 patients with common predictors of longer survival, such as inactive extracranial tumors and younger age. The other 46 patients with 54 brain metastases did not undergo HBO (non-HBO group). Radiation-induced brain injuries were divided into two categories, white matter injury (WMI) and radiation necrosis (RN), on the basis of imaging findings. Results: Radiation-induced brain injury occurred in 5 lesions (11%) in the HBO group (2 WMIs and 3 RNs) and in 11 (20%) in the non-HBO group (9 WMIs and 2 RNs). The WMI was less frequent for the HBO group than for the non-HBO group (p = 0.05), although multivariate analysis by logistic regression showed that WMI was not significantly correlated with HBO (p = 0.07). The 1-year actuarial probability of WMI was significantly better for the HBO group (2%) than for the non-HBO group (36%) (p < 0.05). Conclusions: The present study showed a potential value of prophylactic HBO for Radiation-induced WMIs, which justifies further evaluation to confirm its definite benefit

  12. Putting on the Brakes: Blocking the Growth of Metastases | Center for Cancer Research

    Science.gov (United States)

    Most of the suffering and death caused by cancer is due, not to the primary tumor, but to the ability of cancer cells to spread throughout the body and to form metastases in other organs. Breast and prostate cancers often have periods of dormancy, which can extend up to 30 years, between the identification and treatment of a primary tumor and the growth of overt metastases. What induces or inhibits metastatic dormancy is unknown, but prolonging this period may improve the survival of patients with these types of cancer.

  13. Homogeneous MGMT immunoreactivity correlates with an unmethylated MGMT promoter status in brain metastases of various solid tumors.

    Directory of Open Access Journals (Sweden)

    Barbara Ingold

    Full Text Available The O(6-methylguanine-methyltransferase (MGMT promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical reports on treating brain metastases with temozolomide describe varying effects. This may be due to the fact that MGMT promoter methylation of brain metastases has not yet been explored in depth. Therefore, we assessed MGMT promoter methylation of various brain metastases including those derived from lung (n = 91, breast (n = 72 kidney (n = 49 and from malignant melanomas (n = 113 by methylation-specific polymerase chain reaction (MS-PCR and MGMT immunoreactivity. Fifty-nine of 199 brain metastases (29.6% revealed a methylated MGMT promoter. The methylation rate was the highest in brain metastases derived from lung carcinomas (46.5% followed by those from breast carcinoma (28.8%, malignant melanoma (24.7% and from renal carcinoma (20%. A significant correlation of homogeneous MGMT-immunoreactivity (>95% MGMT positive tumor cells and an unmethylated MGMT promoter was found. Promoter methylation was detected in 26 of 61 (43% tumors lacking MGMT immunoreactivity, in 17 of 63 (27% metastases with heterogeneous MGMT expression, but only in 5 of 54 brain metastases (9% showing a homogeneous MGMT immunoreactivity. Our results demonstrate that a significant number of brain metastases reveal a methylated MGMT-promoter. Based on an obvious correlation between homogeneous MGMT immunoreactivity and unmethylated MGMT promoter, we hypothesize that immunohistochemistry for MGMT may be a helpful diagnostic tool to identify those tumors that probably will not benefit from the use of alkylating agents. The discrepancy between promoter methylation and a lack of MGMT immunoreactivity argues for assessing MGMT promoter methylation both by immunohistochemical as well as by molecular approaches for diagnostic purposes.

  14. 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.)

  15. Bone scintilography for detection of breast cancer metastases

    International Nuclear Information System (INIS)

    Silva Neto, J.B. da; Fontes, C.E.M.; Serson, D.; Oliveira Nunes, J.E. de; Quadros, J.

    1979-01-01

    Eighty seven patiensts with mammary carcinoma and positive skeletal scintigram were submitted to a roentgenologic study to determine the accuracy of the scintigram findings. The skeletal roentgenograms performed immediately after the scintigram confirmed osseous metastases in 60.9% of the cases, after 3 months in 76.5%, after 6 months in 81.5% and, finally, after 12 months the metastases were radiologically confirmed in 89.3% of the cases. The reasons of no confirmation of metastases in 10.7% of the cases are discussed. (Author) [pt

  16. {sup 18}F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Chunjing; Mi, Baoming; Wan, Weixing [Affiliated Hospital of Jiangnan University (Wuxi No. 4 People' s Hospital), Department of Nuclear Medicine, Wuxi (China); Pan, Donghui; Xu, Yuping; Yang, Min [Jiangsu Institute of Nuclear Medicine, Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Wuxi (China); Lang, Lixin; Niu, Gang; Chen, Xiaoyuan [National Institutes of Health, Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States)

    2015-12-15

    We report the biodistribution and radiation dosimetry of an integrin α{sub v}β{sub 3} specific PET tracer {sup 18}F-AlF-NOTA-E[PEG{sub 4}-c(RGDfk)]{sub 2} (denoted as {sup 18}F-Alfatide II). We also assessed the value of {sup 18}F-Alfatide II in patients with brain metastases. A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of {sup 18}F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with {sup 18}F-FDG (5.55 MBq/kg) and {sup 18}F-Alfatide II. Injection of {sup 18}F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. {sup 18}F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by {sup 18}F-Alfatide II PET, while only ten lesions were visualized by {sup 18}F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that {sup 18}F-Alfatide II is feasible for human studies. {sup 18}F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  17. An analysis of the relationship between metastases and cachexia in lung cancer patients.

    Science.gov (United States)

    Shiono, Masatoshi; Huang, Kan; Downey, Robert J; Consul, Nikita; Villanueva, Nicolas; Beck, Kristen; Fenn, Kathleen; Dietz, Donald; Yamaguchi, Takuhiro; Kato, Shunsuke; Divgi, Chaitanya; Kalinsky, Kevin; Wei, Ying; Zhang, Yuan; Borczuk, Alain C; Inoue, Akira; Halmos, Balazs; Acharyya, Swarnali

    2016-09-01

    Weight loss and hematogenous metastases are poor prognosis factors in lung cancer patients that can but do not necessarily co-occur. We retrospectively investigated the clinical association between cachexia, tumor characteristics (such as metastatic burden and mutational status), and treatment in lung cancer patients. The medical records of 394 lung cancer patients from two institutions (Columbia University, USA and Tohoku University, Japan) were reviewed. Information collected included the presence of cachexia, histologic subtype, tumor stage, number of metastases, mutation status, treatment, and survival. Descriptive statistics were performed. Only stage IV patients exhibited >5% weight loss (0.8%, 2.2%, 3.6%, and 5.1%, for stages I to IV; P = 0.0001). Patients with metastases developed cachexia more often than patients without metastases independent of treatment (6.0% and 7.1% weight loss in patients with metastases vs. 2.5% and 2.0% in patients without metastases, before [P = 0.0001] and after [P cachexia had worse survival than patients without cachexia (hazard ratio, 2.94; 95% confidence interval, 2.08-4.16; P cachexia might be linked intrinsically and are independent of treatments administered. KRAS-mutated tumors were more commonly associated with cachexia. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  18. Recurrent spinal primitive neuroectodermal tumor with brain and bone metastases: A case report.

    Science.gov (United States)

    Chen, Frank; Chiou, Shyh-Shin; Lin, Sheng-Fung; Lieu, Ann-Shung; Chen, Yi-Ting; Huang, Chih-Jen

    2017-11-01

    Primary spinal primitive neuroectodermal tumor (PNET) is relatively rare in all age groups, and the prognosis in most cases of spinal PNETs appears to be poor, with a median patient survival of 1 to 2 years. We present a case with recurrent spinal PNET with brain and bone metastases that was successfully treated by multimodality treatment. A 14-year-old teenage girl had suffered from progressive left upper back pain with bilateral lower legs weakness and numbness for 1 year. After treatment, left neck mass was noted 3 years later. Initially, magnetic resonance imaging (MRI) showed neurogenic tumor involving intradural extramedullary space of T5-T10. Pathology report showed PNET (World Health Organization grade IV) featuring lobules of neoplastic cells with round regular nuclei, high nucleus-to-cytoplasm ratio, and fibrillary cytoplasm. At the time of tumor recurrence, chest MRI then showed recurrent tumor at T2-T3 level of the epidural space with right neural foramina invasion. Brain MRI showed extensive bilateral calvarial metastases and leptomeningeal metastases in the right frontoparietal regions. Bone scan showed multiple bone metastases. T-spine tumor removal and adjuvant radiotherapy (RT) to T-spine tumor bed were performed in the initial treatment. After clinical tumor recurrence, tumor removal was done again. She then received chemotherapy followed by whole brain irradiation with hippocampal sparing with 35 gray in 20 fractions. After treatment, follow-up images showed that the disease was under control. There was no neurological sequela. She has survived more than 7 years from diagnosis and more than 4 years from recurrence to date. Multimodality treatments including operation, RT, and chemotherapy should be considered in the initial treatment planning, and salvage chemotherapy was useful in this case.

  19. Incidence and sites of distant metastases from head and neck cancer.

    Science.gov (United States)

    Ferlito, A; Shaha, A R; Silver, C E; Rinaldo, A; Mondin, V

    2001-01-01

    . Extensive evaluation for distant metastases is justified for these tumors. Knowledge of the natural history of various neoplasms and the factors that contribute to distant metastases as well as good judgement are essential for cost-effective treatment planning and decision-making with regard to pre- and postoperative evaluation for distant metastases in cancer of the head and neck. Copyright 2001 S. Karger AG, Basel

  20. Predictors of Survival in Contemporary Practice After Initial Radiosurgery for Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Likhacheva, Anna; Pinnix, Chelsea C. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Parikh, Neil R. [Baylor College of Medicine, Houston, Texas (United States); Allen, Pamela K.; McAleer, Mary F. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chiu, Max S. [University of Nebraska-Lincoln, Lincoln, Nebraska (United States); Sulman, Erik P.; Mahajan, Anita [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Guha-Thakurta, Nandita [Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Prabhu, Sujit S. [Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cahill, Daniel P. [Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Luo, Dershan; Shiu, Almon S. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Brown, Paul D. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Eric L., E-mail: eric.chang@med.usc.edu [Department of Radiation Oncology, University of Southern California, Los Angeles, Los Angeles, California (United States)

    2013-03-01

    Purpose: The number of brain metastases (BM) is a major consideration in determining patient eligibility for stereotactic radiosurgery (SRS), but the evidence for this popular practice is equivocal. The purpose of this study was to determine whether, following multivariate adjustment, the number and volume of BM held prognostic significance in a cohort of patients initially treated with SRS alone. Methods and Materials: A total of 251 patients with primary malignancies, including non-small cell lung cancer (34%), melanoma (30%), and breast carcinoma (16%), underwent SRS for initial treatment of BM. SRS was used as the sole management (62% of patients) or was combined with salvage treatment with SRS (22%), whole-brain radiation therapy (WBRT; 13%), or resection (3%). Median follow-up time was 9.4 months. Survival was determined using the Kaplan-Meier method. Cox regression was used to assess the effects of patient factors on distant brain failure (DBF), local control (LC), and overall survival (OS). Results: LC at 1 year was 94.6%, and median time to DBF was 10 months. Median OS was 11.1 months. On multivariate analysis, statistically significant predictors of OS were presence of extracranial disease (hazard ratio [HR], 4.2, P<.001), total tumor volume greater than 2 cm{sup 3} (HR, 1.98; P<.001), age ≥60 years (HR, 1.67; P=.002), and diagnosis-specific graded prognostic assessment (HR, 0.71; P<.001). The presence of extracranial disease was a statistically significant predictor of DBF (HR, 2.15), and tumor volume was predictive of LC (HR, 4.56 for total volume >2 cm{sup 3}). The number of BM was not predictive of DBF, LC, or OS. Conclusions: The number of BM is not a strong predictor for clinical outcomes following initial SRS for newly diagnosed BM. Other factors including total treatment volume and systemic disease status are better determinants of outcome and may facilitate appropriate use of SRS or WBRT.

  1. Soft tissue metastases from differentiated thyroid cancer diagnosed by {sup 18}F FDG PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Califano, Ines; Quildrian, Sergio; Otero, Jose; Coduti, Martin; Califano, Leonardo; Rojas Bilbao, Erica, E-mail: ines.m.califano@gmail.com [Instituto de Oncologia Angel H. Roffo, Universidad de Buenos Aires (Argentina)

    2013-06-15

    Distant metastases of differentiated thyroid cancer are unusual; lung and bones are the most frequently affected sites. Soft tissue metastases (STM) are extremely rare. We describe two cases of patients with differentiated thyroid cancer metastasizing to soft tissues. Both patients had widespread metastatic disease; clinically asymptomatic soft tissue metastases were found by 18-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F FDG PET-CT), and confirmed by cytological and/or histopathological studies. These findings underscore the ability of {sup 18}F FDG PET-CT in accurately assessing the extent of the disease, as well as the utility of the method to evaluate regions of the body that are not routinely explored. (author)

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

    Science.gov (United States)

    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

  3. Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

    International Nuclear Information System (INIS)

    Roth, Eira S; Fetzer, David T; Barron, Bruce J; Joseph, Usha A; Gayed, Isis W; Wan, David Q

    2009-01-01

    It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis. We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18 F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression. No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does

  4. Novel Approaches to Breast Cancer Prevention and Inhibition of Metastases

    Science.gov (United States)

    2015-10-01

    widespread epithelial hyperplasia (Figure 1a) as well as low and high grade mammary W81XWH-12-1-0093 / Penninger 8 intraepithelial neoplasias (MIN) and...system, expression of oncogenic dRasV12 in the eye epithelium results in a rough adult eye phenotype due to epithelial hyperplasia that can be then...metastases of epithelial tumors, a finding that provided a mechanistic underpinning for clinical trials to delay bone metastases in prostate and breast

  5. Stereotactic radiosurgery for the treatment of brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Hiyama, Hirofumi; Arai, Koji; Izawa, Masahiro; Takakura, Kintomo [Tokyo Women`s Medical Coll. (Japan). Neurological Inst.

    1996-02-01

    The treatment outcome of the metastatic brain tumor in Tokyo Women`s Medical College was reported, and it was described on present state and problem of radiosurgery (RS). One hundred five lesions of 50 patients (male 36, female 12, age 27-85 years) undertaken RS by gamma knife were studied. The primary lesions were the lungs in 23 patients, digestive tract in 12, mammary gland in 4, kidney in 3, thyroid gland in 13, prostate gland in 2 and the other in 3. Thirty nine patients had primary tumor, and 11 patients had recurrent tumor. The volume of 105 lesions was 0.03-56 ml (mean 6.4 ml), and the treatment was carried out for these tumors at average maximum dose 47Gy, average limbic dosage 23Gy. In the image findings, elimination of 46 lesions (44%), reduction of 39 lesions (37%), unchangeable 7 lesions (7%), increase of 13 lesions (13%) were recognized, and tumor reduction rate 81%, local control rate 88% were obtained. The local control rate was around 90% of the tumor, which seize was 15 ml or less. After the treatment, radionecrosis were suspected in 2 lesions of 1 patient. Appearance or aggravation of the edema by the radiation were observed 1-2 month after the treatment in 6 lesions of 5 patients. By the treatment, the following were improved: the hemiplegia in 9 patients, the aphasia in 2, the vertigo in 3. On prognosis, 21 of 46 patients except for the uncertain 4 were alive and 25 died. Through RS is the therapy which is very effective for the metastatic brain tumor, it also exists on some problems to be reached. (A.N.).

  6. THE ABILITY OF CONTRAST-ENHANCED ULTRASOUND IN THE DIAGNOSIS OF LIVER METASTASES IN CERVICAL CANCER

    OpenAIRE

    V. S. Kryazheva; M. A. Chekalova; Z. R-B. Musaeva; V. V. Kuznetsov

    2017-01-01

    Objective: to explore the possibilities of contrast-enhanced ultrasound (CEUS) in the diagnosis of liver metastases in patients with a diagnosis of cervical cancer.Materials and methods. We analyzed the results of 4 clinical cases, of which 3 cases according CEUS diagnosed with liver metastases, in 1 case – nodular hyperplasia.Results and conclusions. Despite the small number of observations, we have concluded that the use of CEUS allows to expand possibilities of the ultrasound method in the...

  7. Sequential surgical resection of hepatic and pulmonary metastases from colorectal cancer

    OpenAIRE

    Limmer, Stefan; Oevermann, Elisabeth; Killaitis, Claudia; Kujath, Peter; Hoffmann, Martin; Bruch, Hans-Peter

    2010-01-01

    Background Resection of isolated hepatic or pulmonary metastases from colorectal cancer is widely accepted and associated with a 5-year survival rate of 25?40%. The value of aggressive surgical management in patients with both hepatic and pulmonary metastases still remains a controversial area. Materials and methods A retrospective review of 1,497 patients with colorectal carcinoma (CRC) was analysed. Of 73 patients identified with resection of CRC and, at some point in time, both liver and l...

  8. Surgical Resection of Brain Metastases and the Risk of Leptomeningeal Recurrence in Patients Treated With Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Johnson, Matthew D.; Avkshtol, Vladimir; Baschnagel, Andrew M.; Meyer, Kurt; Ye, Hong; Grills, Inga S.; Chen, Peter Y.; Maitz, Ann; Olson, Rick E.; Pieper, Daniel R.; Krauss, Daniel J.

    2016-01-01

    Purpose: Recent prospective data have shown that patients with solitary or oligometastatic disease to the brain may be treated with upfront stereotactic radiosurgery (SRS) with deferral of whole-brain radiation therapy (WBRT). This has been extrapolated to the treatment of patients with resected lesions. The aim of this study was to assess the risk of leptomeningeal disease (LMD) in patients treated with SRS to the postsurgical resection cavity for brain metastases compared with patients treated with SRS to intact metastases. Methods and Materials: Four hundred sixty-five patients treated with SRS without upfront WBRT at a single institution were identified; 330 of these with at least 3 months' follow-up were included in this analysis. One hundred twelve patients had undergone surgical resection of at least 1 lesion before SRS compared with 218 treated for intact metastases. Time to LMD and overall survival (OS) time were estimated from date of radiosurgery, and LMD was analyzed by the use of cumulative incidence method with death as a competing risk. Univariate and multivariate analyses were performed with competing risk regression to determine whether various clinical factors predicted for LMD. Results: With a median follow-up time of 9.0 months, 39 patients (12%) experienced LMD at a median of 6.0 months after SRS. At 1 year, the cumulative incidence of LMD, with death as a competing risk, was 5.2% for the patients without surgical resection versus 16.9% for those treated with surgery (Gray test, P<.01). On multivariate analysis, prior surgical resection (P<.01) and breast cancer primary (P=.03) were significant predictors of LMD development. The median OS times for patients undergoing surgery compared with SRS alone were 12.9 and 10.6 months, respectively (log-rank P=.06). Conclusions: In patients undergoing SRS with deferral of upfront WBRT for intracranial metastatic disease, prior surgical resection and breast cancer primary are associated with an

  9. The level of serum tumor makers and bone metastases of lung cancer correlation

    International Nuclear Information System (INIS)

    Li Li; Jin Jianhua

    2014-01-01

    Objective: To study the correlation between the level of serum tumor makers and bone metastases of lung cancer. Method: In 128 diagnosed patients with lung cancer, small cell lung cancer were 26 cases, non-small cell lung cancer were 102 cases which included 44 cases of adenocarcinoma, 50 cases of squamous cell carcinoma, 4 cases of large cell carcinoma, 4 cases of squamous adenocarcinoma. "9"9"mTc-MDP whole-body bone scanning was performed in 128 patients with lung cancer. over the same period, the serum samples were collected in these patients and 30 comparison controls. CEA, CA125, CA199, SCC, NSE, CA15-3, and AFP were measured by ELISA technique. Bone imaging findings analysis used t-test, and serum levels of tumor markers analysis used χ"2 test. Results: The diagnostic of 53 cases of lung cancer with bone metastasis was subject to clinical criteria of lung cancer with bone metastases. The positive ratio of patients with osseous metastasis was confirmed by "9"9"mTc-MDP whole-body bone scanning was 23.44% (30/128), including 16 cases of lung adenocarcinoma, 9 cases of squamous cell carcinoma, 3 cases of small cell lung cancer , 1 case of large cell lung cancer, 1 case of squamous adenocarcinoma and multiple bone metastases accounted for 66.67% (20/30). The levels of serum CEA, CA125, CA199, SCC, NSE and CA15-3 were higher than the control group (P < O.05). 29 cases of CEA positive and 21 cases of CA125 positive were included in 30 cases of lung cancer with bone metastasis. There was a significant difference between the levels of CEA, CA125, CA199, NSE in lung cancer with bone metastases and without bone metastases (P < 0.05). The sensitivity of "9"9"mTc-MDP whole-body bone scanning in diagnosis of lung cancer with bone metastasis was 84.91%. Conclusion: The average value of CEA, CA125, and CA199, SCC, NSE and CA15-3 in lung cancer patients were significantly higher than the control group. In addition, there is a significantly correlation between the occurrence

  10. Endometrial and cervical metastases leading to the diagnosis of a primary breast cancer: A case report

    Directory of Open Access Journals (Sweden)

    E Chupryna

    2017-10-01

    Full Text Available Breast cancer can metastasize to a vast array of organs, but in rare cases cancer can form secondary lesions in the uterus and cervix. In our case report we have a 56 years old female with gynaecologic bleeding, bloating, and difficulty in breathing, fatigue, weakness and polyuria. After performing of dilatation and curettage the result was endometrial and cervical metastases which show histopathological and immunohistochemical results suggesting invasive lobular carcinoma of the breast that leads to primary breast cancer. The treatment was estimated on the basis of her status.

  11. Research of bone metastases in prostate cancer: scintigraphy and radiological study

    International Nuclear Information System (INIS)

    Seibel, I.; Monteiro, T.S.

    1981-01-01

    This paper analyses the results of bone scan and radiologic study of the bones on the search of metastases of prostate cancer seen in the last two years. In 44 patients with prostatic cancer the diagnostic of metastatic disease was made by the 99m Tc scan in 52%, and by the metastatic radiologic survey in only 25%. (author)

  12. Prognostic indices for brain metastases – usefulness and challenges

    Directory of Open Access Journals (Sweden)

    Nieder Carsten

    2009-03-01

    Full Text Available Abstract Background This review addresses the strengths and weaknesses of 6 different prognostic indices, published since the Radiation Therapy Oncology Group (RTOG developed and validated the widely used 3-tiered prognostic index known as recursive partitioning analysis (RPA classes, i.e. between 1997 and 2008. In addition, other analyses of prognostic factors in groups of patients, which typically are underrepresented in large trials or databases, published in the same time period are reviewed. Methods Based on a systematic literature search, studies with more than 20 patients were included. The methods and results of prognostic factor analyses were extracted and compared. The authors discuss why current data suggest a need for a more refined index than RPA. Results So far, none of the indices has been derived from analyses of all potential prognostic factors. The 3 most recently published indices, including the RTOG's graded prognostic assessment (GPA, all expanded from the primary 3-tiered RPA system to a 4-tiered system. The authors' own data confirm the results of the RTOG GPA analysis and support further evaluation of this tool. Conclusion This review provides a basis for further refinement of the current prognostic indices by identifying open questions regarding, e.g., performance of the ideal index, evaluation of new candidate parameters, and separate analyses for different cancer types. Unusual primary tumors and their potential differences in biology or unique treatment approaches are not well represented in large pooled analyses.

  13. Recursive partitioning analysis (RPA) classification predicts survival in patients with brain metastases from sarcoma.

    Science.gov (United States)

    Grossman, Rachel; Ram, Zvi

    2014-12-01

    Sarcoma rarely metastasizes to the brain, and there are no specific treatment guidelines for these tumors. The recursive partitioning analysis (RPA) classification is a well-established prognostic scale used in many malignancies. In this study we assessed the clinical characteristics of metastatic sarcoma to the brain and the validity of the RPA classification system in a subset of 21 patients who underwent surgical resection of metastatic sarcoma to the brain We retrospectively analyzed the medical, radiological, surgical, pathological, and follow-up clinical records of 21 patients who were operated for metastatic sarcoma to the brain between 1996 and 2012. Gliosarcomas, sarcomas of the head and neck with local extension into the brain, and metastatic sarcomas to the spine were excluded from this reported series. The patients' mean age was 49.6 ± 14.2 years (range, 25-75 years) at the time of diagnosis. Sixteen patients had a known history of systemic sarcoma, mostly in the extremities, and had previously received systemic chemotherapy and radiation therapy for their primary tumor. The mean maximal tumor diameter in the brain was 4.9 ± 1.7 cm (range 1.7-7.2 cm). The group's median preoperative Karnofsky Performance Scale was 80, with 14 patients presenting with Karnofsky Performance Scale of 70 or greater. The median overall survival was 7 months (range 0.2-204 months). The median survival time stratified by the Radiation Therapy Oncology Group RPA classes were 31, 7, and 2 months for RPA class I, II, and III, respectively (P = 0.0001). This analysis is the first to support the prognostic utility of the Radiation Therapy Oncology Group RPA classification for sarcoma brain metastases and may be used as a treatment guideline tool in this rare disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Overexpression of β1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases

    International Nuclear Information System (INIS)

    Fujita, Manabu; Khazenzon, Natalya M; Bose, Shikha; Sekiguchi, Kiyotoshi; Sasaki, Takako; Carter, William G; Ljubimov, Alexander V; Black, Keith L; Ljubimova, Julia Y

    2005-01-01

    Laminins are the major components of vascular and parenchymal basement membranes. We previously documented a switch in the expression of vascular laminins containing the α4 chain from predominantly laminin-9 (α4β2γ1) to predominantly laminin-8 (α4β1γ1) during progression of human brain gliomas to high-grade glioblastoma multiforme. Here, differential expression of laminins was studied in blood vessels and ductal epithelium of the breast. In the present study the expressions of laminin isoforms α1–α5, β1–β3, γ1, and γ2 were examined during progression of breast cancer. Forty-five clinical samples of breast tissues including normal breast, ductal carcinomas in situ, invasive ductal carcinomas, and their metastases to the brain were compared using Western blot analysis and immunohistochemistry for various chains of laminin, in particular laminin-8 and laminin-9. Laminin α4 chain was observed in vascular basement membranes of most studied tissues, with the highest expression in metastases. At the same time, the expression of laminin β2 chain (a constituent of laminin-9) was mostly seen in normal breast and carcinomas in situ but not in invasive carcinomas or metastases. In contrast, laminin β1 chain (a constituent of laminin-8) was typically found in vessel walls of carcinomas and their metastases but not in those of normal breast. The expression of laminin-8 increased in a progression-dependent manner. A similar change was observed from laminin-11 (α5β2γ1) to laminin-10 (α5β1γ1) during breast tumor progression. Additionally, laminin-2 (α2β1γ1) appeared in vascular basement membranes of invasive carcinomas and metastases. Chains of laminin-5 (α3β3γ2) were expressed in the ductal epithelium basement membranes of the breast and diminished with tumor progression. These results suggest that laminin-2, laminin-8, and laminin-10 are important components of tumor microvessels and may associate with breast tumor progression. Angiogenic switch

  15. Overexpression of β1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases

    Science.gov (United States)

    Fujita, Manabu; Khazenzon, Natalya M; Bose, Shikha; Sekiguchi, Kiyotoshi; Sasaki, Takako; Carter, William G; Ljubimov, Alexander V; Black, Keith L; Ljubimova, Julia Y

    2005-01-01

    Introduction Laminins are the major components of vascular and parenchymal basement membranes. We previously documented a switch in the expression of vascular laminins containing the α4 chain from predominantly laminin-9 (α4β2γ1) to predominantly laminin-8 (α4β1γ1) during progression of human brain gliomas to high-grade glioblastoma multiforme. Here, differential expression of laminins was studied in blood vessels and ductal epithelium of the breast. Method In the present study the expressions of laminin isoforms α1–α5, β1–β3, γ1, and γ2 were examined during progression of breast cancer. Forty-five clinical samples of breast tissues including normal breast, ductal carcinomas in situ, invasive ductal carcinomas, and their metastases to the brain were compared using Western blot analysis and immunohistochemistry for various chains of laminin, in particular laminin-8 and laminin-9. Results Laminin α4 chain was observed in vascular basement membranes of most studied tissues, with the highest expression in metastases. At the same time, the expression of laminin β2 chain (a constituent of laminin-9) was mostly seen in normal breast and carcinomas in situ but not in invasive carcinomas or metastases. In contrast, laminin β1 chain (a constituent of laminin-8) was typically found in vessel walls of carcinomas and their metastases but not in those of normal breast. The expression of laminin-8 increased in a progression-dependent manner. A similar change was observed from laminin-11 (α5β2γ1) to laminin-10 (α5β1γ1) during breast tumor progression. Additionally, laminin-2 (α2β1γ1) appeared in vascular basement membranes of invasive carcinomas and metastases. Chains of laminin-5 (α3β3γ2) were expressed in the ductal epithelium basement membranes of the breast and diminished with tumor progression. Conclusion These results suggest that laminin-2, laminin-8, and laminin-10 are important components of tumor microvessels and may associate with breast

  16. Early PET/CT after radiofrequency ablation in colorectal cancer liver metastases: is it useful?

    Institute of Scientific and Technical Information of China (English)

    LIU Zhao-yu; CHANG Zhi-hui; LU Zai-ming; GUO Qi-yong

    2010-01-01

    Background Morphologic imaging after radiofrequency ablation (RFA) of liver metastases is hampered by an inflammatory response in the ablation margin, making the identification of local tumor progression (LTP) difficult. The aim of this study was to evaluate the efficacy of early 18F-FDG PET/CT scanning to monitor the effectiveness of RFA in colorectal liver metastases.Methods Twelve patients with 20 metastases were treated with RFA for colorectal liver metastases. They underwent PET/CT within 2 weeks before RFA and within 24 hours after RFA (so termed "early PET/CT"). PET/CT was repeated at 1, 3, and 6 months, and then every 6 months after ablation. The standard of reference was based on available clinical and radiological follow-up data.Results Early PET/CT revealed total photopenia in 16 RFA-treated metastases, which were found to be without residual tumor on the final PET/CT scan. Three RFA-treated metastases with focal uptake were identified as local tumor progression, which necessitated further treatment. One RFA-treated metastasis with rim-shaped uptake was regarded as inflammation. The results of the early PET/CT scanning were consistent with the findings of the final follow-up. Conclusions PET/CT performed within 24 hours after RFA can effectively detect whether residual tumor exists for colorectal cancer liver metastases. The results can guide further treatment, and may improve the efficacy of RFA.

  17. Effective treatment of the brachial plexus syndrome in breast cancer patients by early detection and control of loco-regional metastases with radiation or systemic therapy

    International Nuclear Information System (INIS)

    Kamenova, B.; Braverman, A.S.; Schwartz, M.; Sohn, C.; Lange, C.; Efiom-Ekaha, D.; Rotman, M.; Yoon, H.

    2009-01-01

    In breast cancer (BC) patients the brachial plexus syndrome (BPS) has been reported to be due to loco-regional metastases or radiation plexopathy. Associated arm edema is considered more suggestive of the latter. Radiation therapy is the only effective treatment for BPS reported. The charts of all BC patients who presented to our clinic from 1982 to 2006 with homolateral arm pain and neurological deficits, without humerus, cervical spine, or brain metastases, were reviewed. There were 28 patients fulfilling these criteria for BPS. Supraclavicular, axillary or chest wall metastases developed synchronously with the BPS in 26 patients; in 21 they were recurrences, found 6-94 months (median 34 months) after primary BC treatment, while in 5 others they were progressing inoperable primary tumors and nodes. Arm edema first occurred at the same time as loco-regional metastases in 19 patients. Treatment for the BPS was administered to 22 patients; it was directed at their loco-regional metastases. The BPS was initially treated with radiation (8 patients) or chemo- or endocrine therapy (14 patients); 19 (86%) had partial or complete remission of pain and neurologic deficits, with an 8-month median duration. The BPS in BC patients is due to loco-regional metastases and is often associated with arm edema. Chemo- or endocrine therapy induced the remission of pain and deficits as frequently as radiation therapy. (author)

  18. Integrin Alpha-v and HER2 in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    ZOOM live cell imaging machine (ESSEN Bioscience; Figure 2). c. Interactions of αv integrin and HER2 in breast cancer brain metastases. We found...HCC1954 breast cancer cells. C) Real time live cell imaging of MM2BH cells treated with cilengitide (0, .3, 1, 3, and 10 µg/mL) using IncuCyte ZOOM

  19. Clinical observation of 89Sr treatment efficacy of multiple bone metastases in breast and prostate cancer patients

    International Nuclear Information System (INIS)

    Yuan Chao; Li Weipeng; Hu Yongquan; Tao Jian

    2010-01-01

    Objective: To evaluate the efficacy of 89 Sr in treatment of multiple bone metastases of breast and prostate cancer patients. Methods: Seventy multiple bone metastases patients (30 females with breast cancer and 40 males with prostate cancer) were treated with 89 Sr. The clinical effectiveness was assessed by Karnofsky performance score and whole body bone scanning data. Results: The total pain relief rate was 79% in bone metastases of breast cancer and 85% in bone metastases of prostate cancer, respectively. There was no significant differences between the two groups (χ 2 =0.78, P>0.05). The Karnofsky score was significantly improved in both groups (t=2.46, P 89 Sr treatment was good, and the quality of life was improved in patients with multiple bone metastases breast or prostate cancer. (authors)

  20. Fractionated stereotactic radiosurgery for patients with skull base metastases from systemic cancer involving the anterior visual pathway

    International Nuclear Information System (INIS)

    Minniti, Giuseppe; Osti, Mattia Falchetto; Maurizi Enrici, Riccardo; Esposito, Vincenzo; Clarke, Enrico; Scaringi, Claudia; Bozzao, Alessandro; Falco, Teresa; De Sanctis, Vitaliana; Enrici, Maurizio Maurizi; Valeriani, Maurizio

    2014-01-01

    To analyze the tumor control, survival outcomes, and toxicity after stereotactic radiosurgery (SRS) for skull base metastases from systemic cancer involving the anterior visual pathway. We have analyzed 34 patients (23 females and 11 males, median age 59 years) who underwent multi-fraction SRS for a skull base metastasis compressing or in close proximity of optic nerves and chiasm. All metastases were treated with frameless LINAC-based multi-fraction SRS in 5 daily fractions of 5 Gy each. Local control, distant failure, and overall survival were estimated using the Kaplan-Meier method calculated from the time of SRS. Prognostic variables were assessed using log-rank and Cox regression analyses. At a median follow-up of 13 months (range, 2–36.5 months), twenty-five patients had died and 9 were alive. The 1-year and 2-year local control rates were 89% and 72%, and respective actuarial survival rates were 63% and 30%. Four patients recurred with a median time to progression of 12 months (range, 6–27 months), and 17 patients had new brain metastases at distant brain sites. The 1-year and 2-year distant failure rates were 50% and 77%, respectively. On multivariate analysis, a Karnofsky performance status (KPS) >70 and the absence of extracranial metastases were prognostic factors associated with lower distant failure rates and longer survival. After multi-fraction SRS, 15 (51%) out of 29 patients had a clinical improvement of their preexisting cranial deficits. No patients developed radiation-induced optic neuropathy during the follow-up. Multi-fraction SRS (5 x 5 Gy) is a safe treatment option associated with good local control and improved cranial nerve symptoms for patients with a skull base metastasis involving the anterior visual pathway

  1. A case of rectal cancer successfully treated with surgery and stereotactic radiotherapy for metachronous lung metastases

    International Nuclear Information System (INIS)

    Oshima, Yu; Hosoda, Yohei; Tachi, Hidekazu

    2016-01-01

    A 64-year-old woman underwent polypectomy for a rectal polyp (Isp). Pathological findings were invasion of the submucosa (3,500 μm diameter), and she underwent anterior resection for rectal cancer (RS, pT1b, pN0, cM0, Stage I ) without adjuvant chemotherapy. Lung masses were found in her right (8 mm) and left lung (7 mm). The tumors enlarged during the 4 month follow-up period. We decided to perform left partial pneumonectomy. The tumor was diagnosed as a lung metastasis from colon cancer by pathology. Because the right tumor was located towards the center, performing right pneumonectomy would have been quite invasive and we feared occult metastases. We decided to apply SRT (50 Gy) to the right tumor. The tumor shrunk and became a scar after treatment. There were no complications such as radiation pneumonitis. The patient was in good health without any recurrence for 12 months after SRT. Surgical resection is an optimal method to control lung metastasis from colon cancer if the lesion is operable. However, in the case of a tumor centrally located, surgical resection may cause deterioration of lung function. There are also cases with contraindications for surgery due to co-morbidities. In addition, there is no consensus on observation periods to exclude occult metastases. SRT can be an effective treatment for lung metastases from colon cancer when there are bilateral lung metastases and no metastases outside the lungs. (author)

  2. Mutational profiles of breast cancer metastases from a rapid autopsy series reveal multiple evolutionary trajectories.

    Science.gov (United States)

    Avigdor, Bracha Erlanger; Cimino-Mathews, Ashley; DeMarzo, Angelo M; Hicks, Jessica L; Shin, James; Sukumar, Saraswati; Fetting, John; Argani, Pedram; Park, Ben H; Wheelan, Sarah J

    2017-12-21

    Heterogeneity within and among tumors in a metastatic cancer patient is a well-established phenomenon that may confound treatment and accurate prognosis. Here, we used whole-exome sequencing to survey metastatic breast cancer tumors from 5 patients in a rapid autopsy program to construct the origin and genetic development of metastases. Metastases were obtained from 5 breast cancer patients using a rapid autopsy protocol and subjected to whole-exome sequencing. Metastases were evaluated for sharing of somatic mutations, correlation of copy number variation and loss of heterozygosity, and genetic similarity scores. Pathological features of the patients' disease were assessed by immunohistochemical analyses. Our data support a monoclonal origin of metastasis in 3 cases, but in 2 cases, metastases arose from at least 2 distinct subclones in the primary tumor. In the latter 2 cases, the primary tumor presented with mixed histologic and pathologic features, suggesting early divergent evolution within the primary tumor with maintenance of metastatic capability in multiple lineages. We used genetic and histopathological evidence to demonstrate that metastases can be derived from a single or multiple independent clones within a primary tumor. This underscores the complexity of breast cancer clonal evolution and has implications for how best to determine and implement therapies for early- and late-stage disease.

  3. Referral patterns of patients with liver metastases due to colorectal cancer for resection.

    LENUS (Irish Health Repository)

    Al-Sahaf, O

    2012-02-01

    INTRODUCTION: Colorectal carcinoma accounts for 10% of cancer deaths in the Western World, with the liver being the most common site of distant metastases. Resection of liver metastases is the treatment of choice, with a 5-year survival rate of 35%. However, only 5-10% of patients are suitable for resection at presentation. AIMS: To examine the referral pattern of patients with liver metastases to a specialist hepatic unit for resection. METHODOLOGY: Retrospective review of patient\\'s charts diagnosed with colorectal liver metastases over a 10-year period. RESULTS: One hundred nine (38 women, 71 men) patients with liver metastases were included, mean age 61 years; 79 and 30 patients had synchronous and metachronus metastases, respectively. Ten criteria for referral were identified; the referral rate was 8.25%, with a resection rate of 0.9%. Forty two percent of the patients had palliative chemotherapy; 42% had symptomatic treatment. CONCLUSION: This study highlights the advanced stage of colorectal cancer at presentation; in light of modern evidence-based, centre-oriented therapy of liver metastasis, we conclude that criteria of referral for resection should be based on the availability of treatment modalities.

  4. Pseudo-Meigs' syndrome secondary to metachronous ovarian metastases from transverse colon cancer.

    Science.gov (United States)

    Kyo, Kennoki; Maema, Atsushi; Shirakawa, Motoaki; Nakamura, Toshio; Koda, Kenji; Yokoyama, Hidetaro

    2016-05-14

    Pseudo-Meigs' syndrome associated with colorectal cancer is extremely rare. We report here a case of pseudo-Meigs' syndrome secondary to metachronous ovarian metastases from colon cancer. A 65-year-old female with a history of surgery for transverse colon cancer and peritoneal dissemination suffered from metachronous ovarian metastases during treatment with systemic chemotherapy. At first, neither ascites nor pleural effusion was observed, but she later complained of progressive abdominal distention and dyspnea caused by rapidly increasing ascites and pleural effusion and rapidly enlarging ovarian metastases. Abdominocenteses were repeated, and cytological examinations of the fluids were all negative for malignant cells. We suspected pseudo-Meigs' syndrome, and bilateral oophorectomies were performed after thorough informed consent. The patient's postoperative condition improved rapidly after surgery. We conclude that pseudo-Meigs' syndrome should be included in the differential diagnosis of massive or rapidly increasing ascites and pleural effusion associated with large or rapidly enlarging ovarian tumors.

  5. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Local tumour control and survival

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, Oliver; Wucherpfennig, David; Prokic, Vesna [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Fels, Franziska [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); St. Josefs Hospital, Department of Radiation Oncology, Offenburg (Germany); Frings, Lars [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); University Hospital Freiburg, Department of Geriatrics and Gerontology, Freiburg (Germany); University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Egger, Karl [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Weyerbrock, Astrid [University Medical Center Freiburg, Department of Neurosurgery, Freiburg (Germany); Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Grosu, Anca-Ligia [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK), Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2015-01-16

    Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D{sub 98} {sub %} to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. D{sub mean} to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration. (orig.) [German] Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusaetzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie praesentieren wir erste Ergebnisse

  6. Radiosurgery for brain metastases: relationship of dose and pattern of enhancement to local control

    International Nuclear Information System (INIS)

    Shiau, C.-Y.; Sneed, Penny K.; Shu, H.-K.G.; Lamborn, Kathleen R.; McDermott, Michael W.; Chang, Susan; Nowak, Peter; Petti, Paula L.; Smith, Vernon; Verhey, Lynn J.; Ho, Maria; Park, Elaine; Wara, William M.; Gutin, Philip H.; Larson, David A.

    1997-01-01

    Purpose: This study aimed to analyze dose, initial pattern of enhancement, and other factors associated with freedom from progression (FFP) of brain metastases after radiosurgery (RS). Methods and Materials: All brain metastases treated with gamma-knife RS at the University of California, San Francisco, from 1991 to 1994 were reviewed. Evaluable lesions were those with follow-up magnetic resonance or computed tomographic imaging. Actuarial FFP was calculated using the Kaplan-Meier method, measuring FFP from the date of RS to the first imaging study showing tumor progression. Controlled lesions were censored at the time of the last imaging study. Multivariate analyses were performed using a stepwise Cox proportional hazards model. Results: Of 261 lesions treated in 119 patients, 219 lesions in 100 patients were evaluable. Major histologies included adenocarcinoma (86 lesions), melanoma (77), renal cell carcinoma (21), and carcinoma not otherwise specified (17). The median prescribed RS dose was 18.5 Gy (range, 10-22) and the median tumor volume was 1.3 ml (range, 0.02-30.9). The initial pattern of contrast enhancement was homogeneous in 68% of lesions, heterogeneous in 12%, and ring-enhancing in 19%. The actuarial FFP was 82% at 6 months and 77% at 1 year for all lesions, and 93 and 90%, respectively, for 145 lesions receiving ≥ 18 Gy. Multivariate analysis showed that longer FFP was significantly associated with higher prescribed RS dose, a homogeneous pattern of contrast enhancement, and a longer interval between primary diagnosis and RS. Adjusted for these factors, adenocarcinomas had longer FFP than melanomas. No significant differences in FFP were noted among lesions undergoing RS for recurrence after prior radiotherapy (119 lesions), RS alone as initial treatment (45), or RS boost (55). Conclusion: A minimum prescribed radiosurgical dose ≥ 18 Gy yields excellent local control of brain metastases. The influence of pattern of enhancement on local control, a

  7. Intrahepatic and systemic therapy with oxaliplatin combined with capecitabine in patients with hepatic metastases from breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D L; Nørgaard, H; Weber Vestermark, Lene

    2012-01-01

    The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease.......The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease....

  8. Neurological Change after Gamma Knife Radiosurgery for Brain Metastases Involving the Motor Cortex

    Science.gov (United States)

    Park, Chang-Yong; Choi, Hyun-Yong; Lee, Sang-Ryul; Roh, Tae Hoon; Seo, Mi-Ra

    2016-01-01

    Background Although Gamma Knife radiosurgery (GKRS) can provide beneficial therapeutic effects for patients with brain metastases, lesions involving the eloquent areas carry a higher risk of neurologic deterioration after treatment, compared to those located in the non-eloquent areas. We aimed to investigate neurological change of the patients with brain metastases involving the motor cortex (MC) and the relevant factors related to neurological deterioration after GKRS. Methods We retrospectively reviewed clinical, radiological and dosimetry data of 51 patients who underwent GKRS for 60 brain metastases involving the MC. Prior to GKRS, motor deficits existed in 26 patients (50.9%). The mean target volume was 3.2 cc (range 0.001–14.1) at the time of GKRS, and the mean prescription dose was 18.6 Gy (range 12–24 Gy). Results The actuarial median survival time from GKRS was 19.2±5.0 months. The calculated local tumor control rates at 6 and 12 months after GKRS were 89.7% and 77.4%, respectively. During the median clinical follow-up duration of 12.3±2.6 months (range 1–54 months), 18 patients (35.3%) experienced new or worsened neurologic deficits with a median onset time of 2.5±0.5 months (range 0.3–9.7 months) after GKRS. Among various factors, prescription dose (>20 Gy) was a significant factor for the new or worsened neurologic deficits in univariate (p=0.027) and multivariate (p=0.034) analysis. The managements of 18 patients were steroid medication (n=10), boost radiation therapy (n=5), and surgery (n=3), and neurological improvement was achieved in 9 (50.0%). Conclusion In our series, prescription dose (>20 Gy) was significantly related to neurological deterioration after GKRS for brain metastases involving the MC. Therefore, we suggest that careful dose adjustment would be required for lesions involving the MC to avoid neurological deterioration requiring additional treatment in the patients with limited life expectancy. PMID:27867921

  9. Intracrainal metastases of lung cancer -CT and histopathologic correlation-

    International Nuclear Information System (INIS)

    Park, Hyun Ju; Kim, Myung Soon; Kang, Myung Jae

    1991-01-01

    The authors retrospectively analyzed high resolution (HR) CT scans of the brain in 23 patients with surgically proved primary lung cancer and intracranial metastatic lesions from April 1986 to March 1990. The purpose of this study was to evaluate the relationship between histopathologic types of primary lung cancer and HRCT findings of brain. The results were as follows: The locations of metastatic lesion were intraaxial in 93% and extraaxial in 7%. In the intraaxial lesions, most were in the supratentorial area (83%) and the remainer in the infratentorial area (10%). Among the supratentorial lesions, the parietal lobe was the most commonly involved (33%), while the second most common location was frontal lobe (22%). The HRCT showed multiple lesions in 52% and solitary lesions in 48%. All cell types except for squamous cell carcinoma showed the same incidence in multiplicity, and the squamous cell carcinoma showed slightly more multiple lesions rather than solitary ones. The degree of peritumoral edema was none in 4%, mild in 25%, moderate in 46%, and severe in 25%. All cell types except for squamous cell carcinoma in general showed a moderate degree of edema, and the squamous cell carcinoma mainly showed mild and severe edema. Precontrast CT scans showed mixed density in 52%, isodensity in 24%, low density in 19%, and high density in 5%. All cell types except for large cell carcinoma showed mixed density, the large cell carcinoma showed a low density unlike the others. Hemorrhages were seen in 24% and noted in all cell types except for large cell carcinoma. Postcontrast CT scans showed ring enhancement in 64%, nodular enhancement in 20%, and inhomogeneous enhancement in 16%. All cell types except for small cell carcinoma generally showed ring enhancement, and the small cell carcinoma showed a variable degree of enhancement

  10. CURRENT POSSIBILITIES OF TREATMENT FOR VISCERAL METASTASES IN PATIENTS WITH METASTATIC CASTRATION-REFRACTORY PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2014-07-01

    Full Text Available Medications increasing the survival of patients with metastatic castration-refractory prostate cancer (CRPC are lacking today. In the past 3 years, in the pharmaceutical market there have been a few novel drugs to treat progressive prostate cancer. Abiraterone acetate is an androgen synthesis inhibitor, which is also used to increase the survival of patients with metastatic CRPC that progresses after chemotherapy. The results of treatment for metastatic CRPC depend on a number of factors. Visceral metastases are poor predictors of the course of the disease. The results of abiraterone acetate treatment were analyzed in CRPC patients with visceral metastases.

  11. Interest of radiotherapy of rectal cancer with synchronous metastases

    International Nuclear Information System (INIS)

    Tournat, H.; Vendrely, V.; Smith, D.; Capdepont, M.; Maire, J.P.; Cherciu, B.; Laurent, C.; Kantor, G.

    2008-01-01

    Purpose: There is no consensus about the treatment of rectal tumour when there are synchronous metastases. The interest of radiotherapy is debated. Patients and methods: Thirty-seven patients with rectal tumour and synchronous metastases were treated with radiotherapy first between September 1994 and December 2004. We analysed the tolerance, local control, resectability, overall survival of such a therapeutic strategy. Results: The mean follow-up was 30 months. Twenty-four tumors were resectable for both the primary site and the metastases. Thirteen were unresectable at the time of diagnosis. Thirty-three patients were treated with radio chemotherapy, ten with radiotherapy alone. Eighty-six decimal five percent of them had no pelvic symptom six weeks after the treatment. Twenty-one rectal tumours were finally resected. The disease progressed in six cases during the radiotherapy. Surgery of the metastases was possible for 12 patients with tumour initially resectable. Conclusion: Radio chemotherapy is a 'tolerable' treatment, in spite of more frequent urinary or digestive side-effects. But, if there is no surgery, palliative effect of radiotherapy is limited. (authors)

  12. Cold metastases detected by bone scintigraphy in aggressive lung cancer

    International Nuclear Information System (INIS)

    Martinez Carsi, C.; Perales Vila, A.; Ruiz Hernandez, G.; Sanchez Marchori, C.; Oro Camps, J.

    1998-01-01

    A case of a 55-year-old man was remitted to Traumatology Department to present back pain of two weeks of evolution. The results of bone scintigraphy and the patient's evolution allowed the diagnosis. This case report and a literature review showed the importance of using a routine bone scan in diagnosis of bone metastases. (orig.) [de

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

    Science.gov (United States)

    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

  14. Prognostic factors of HER2-positive breast cancer patients who develop brain metastasis: a multicenter retrospective analysis.

    Science.gov (United States)

    Hayashi, Naoki; Niikura, Naoki; Masuda, Norikazu; Takashima, Seiki; Nakamura, Rikiya; Watanabe, Ken-ichi; Kanbayashi, Chizuko; Ishida, Mayumi; Hozumi, Yasuo; Tsuneizumi, Michiko; Kondo, Naoto; Naito, Yoichi; Honda, Yayoi; Matsui, Akira; Fujisawa, Tomomi; Oshitanai, Risa; Yasojima, Hiroyuki; Yamauchi, Hideko; Saji, Shigehira; Iwata, Hiroji

    2015-01-01

    The clinical course and prognostic factors of HER2-positive breast cancer patients with brain metastases are not well known because of the relatively small population. The aim of this study was to determine prognostic factors associated with HER2-positive patients who develop brain metastases. This retrospective study assessed the largest dataset to date of 432 HER2-positive patients who were diagnosed with brain metastases from 24 institutions of the Japan Clinical Oncology Group, Breast Cancer Study Group. The median age of the 432 patients was 54 years (range, 20-86 years). Of the patients, 162 patients (37.5 %) had ER-positive/HER2-positive (ER+HER2+) breast cancer, and 270 (62.5 %) had ER-negative/HER2-positive (ER-HER2+) breast cancer. The median brain metastasis-free survival period from primary breast cancer was 33.5 months in both groups. The median survival after developing brain metastasis was 16.5 and 11.5 months in the ER+HER2+ and ER-HER2+ groups, respectively, (p = 0.117). Patients with >3 brain metastases had significantly shorter overall survival in both ER+HER2+ (p developing brain metastases was not associated with survival duration after developing brain metastases (p = 0.571). However, patients treated with both trastuzumab and lapatinib after developing metastasis had significantly longer survival than patients treated with trastuzumab alone, lapatinib alone, or no HER2-targeting agent (p brain metastases, regardless of the use of trastuzumab before developing brain metastasis, treatment with both trastuzumab and lapatinib might improve survival.

  15. Changes in the renin angiotensin system during the development of colorectal cancer liver metastases

    International Nuclear Information System (INIS)

    Neo, Jaclyn H; Ager, Eleanor I; Angus, Peter W; Zhu, Jin; Herath, Chandana B; Christophi, Christopher

    2010-01-01

    Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease. Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software. Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen. These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade

  16. What Is the Optimal Treatment of Large Brain Metastases? An Argument for a Multidisciplinary Approach

    International Nuclear Information System (INIS)

    Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.; Adler, John R.; Harsh, Griffith R.; Atalar, Banu; Lieberson, Robert E.; Soltys, Scott G.

    2012-01-01

    Purpose: Single-modality treatment of large brain metastases (>2 cm) with whole-brain irradiation, stereotactic radiosurgery (SRS) alone, or surgery alone is not effective, with local failure (LF) rates of 50% to 90%. Our goal was to improve local control (LC) by using multimodality therapy of surgery and adjuvant SRS targeting the resection cavity. Patients and Methods: We retrospectively evaluated 97 patients with brain metastases >2 cm in diameter treated with surgery and cavity SRS. Local and distant brain failure (DF) rates were analyzed with competing risk analysis, with death as a competing risk. The overall survival rate was calculated by the Kaplain-Meier product-limit method. Results: The median imaging follow-up duration for all patients was 10 months (range, 1–80 months). The 12-month cumulative incidence rates of LF, with death as a competing risk, were 9.3% (95% confidence interval [CI], 4.5%–16.1%), and the median time to LF was 6 months (range, 3–17 months). The 12-month cumulative incidence rate of DF, with death as a competing risk, was 53% (95% CI, 43%–63%). The median survival time for all patients was 15.6 months. The median survival times for recursive partitioning analysis classes 1, 2, and 3 were 33.8, 13.7, and 9.0 months, respectively (p = 0.022). On multivariate analysis, Karnofsky Performance Status (≥80 vs. <80; hazard ratio 0.54; 95% CI 0.31–0.94; p = 0.029) and maximum preoperative tumor diameter (hazard ratio 1.41; 95% CI 1.08–1.85; p = 0.013) were associated with survival. Five patients (5%) required intervention for Common Terminology Criteria for Adverse Events v4.02 grade 2 and 3 toxicity. Conclusion: Surgery and adjuvant resection cavity SRS yields excellent LC of large brain metastases. Compared with other multimodality treatment options, this approach allows patients to avoid or delay whole-brain irradiation without compromising LC.

  17. Prognostic factors derived from recursive partition analysis (RPA) of radiation therapy oncology group (RTOG) brain metastases trials applied to surgically resected and irradiated brain metastatic cases

    International Nuclear Information System (INIS)

    Agboola, Olusegun; Benoit, Brien; Cross, Peter; Silva, Vasco da; Esche, Bernd; Lesiuk, Howard; Gonsalves, Carol

    1998-01-01

    Purpose: (a) To identify the prognostic factors that determine survival after surgical resection and irradiation of tumors metastatic to brain. (b) To determine if the prognostic factors used in the recursive partition analysis (RPA) of brain metastases cases from Radiation Therapy Oncology Group (RTOG) studies into three distinct survival classes is applicable to surgically resected and irradiated patients. Method: The medical records of 125 patients who had surgical resection and radiotherapy for brain metastases from 1985 to 1997 were reviewed. The patients' disease and treatment related factors were analyzed to identify factors that independently determine survival after diagnosis of brain metastasis. The patients were also grouped into three classes using the RPA-derived prognostic parameters which are: age, performance status, state of the primary disease, and presence or absence of extracranial metastases. Class 1: patients ≤ 65 years of age, Karnofsky performance status (KPS) of ≥70, with controlled primary disease and no extracranial metastases; Class 3: patients with KPS < 70. Patients who do not qualify for Class 1 or 3 are grouped as Class 2. The survival of these patients was determined from the time of diagnosis of brain metastases to the time of death. Results: The median survival of the entire group was 9.5 months. The three classes of patients as grouped had median survivals of 14.8, 9.9, and 6.0 months respectively (p = 0.0002). Age of < 65 years, KPS of ≥ 70, controlled primary disease, absence of extracranial metastases, complete surgical resection of the brain lesion(s) were found to be independent prognostic factors for survival; the total dose of radiation was not. Conclusion: Based on the results of this study, the patients and disease characteristics have significant impact on the survival of patients with brain metastases treated with a combination of surgical resection and radiotherapy. These parameters could be used in selecting

  18. Breast Cancer-Derived Lung Metastases Show Increased Pyruvate Carboxylase-Dependent Anaplerosis

    Directory of Open Access Journals (Sweden)

    Stefan Christen

    2016-10-01

    Full Text Available Cellular proliferation depends on refilling the tricarboxylic acid (TCA cycle to support biomass production (anaplerosis. The two major anaplerotic pathways in cells are pyruvate conversion to oxaloacetate via pyruvate carboxylase (PC and glutamine conversion to α-ketoglutarate. Cancers often show an organ-specific reliance on either pathway. However, it remains unknown whether they adapt their mode of anaplerosis when metastasizing to a distant organ. We measured PC-dependent anaplerosis in breast-cancer-derived lung metastases compared to their primary cancers using in vivo 13C tracer analysis. We discovered that lung metastases have higher PC-dependent anaplerosis compared to primary breast cancers. Based on in vitro analysis and a mathematical model for the determination of compartment-specific metabolite concentrations, we found that mitochondrial pyruvate concentrations can promote PC-dependent anaplerosis via enzyme kinetics. In conclusion, we show that breast cancer cells proliferating as lung metastases activate PC-dependent anaplerosis in response to the lung microenvironment.

  19. Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases

    International Nuclear Information System (INIS)

    Gaspar, Laurie E.; Scott, Charles; Murray, Kevin; Curran, Walter

    2000-01-01

    Purpose: The Radiation Therapy Oncology Group (RTOG) previously developed three prognostic classes for brain metastases using recursive partitioning analysis (RPA) of a large database. These classes were based on Karnofsky performance status (KPS), primary tumor status, presence of extracranial system metastases, and age. An analysis of RTOG 91-04, a randomized study comparing two dose-fractionation schemes with a comparison to the established RTOG database, was considered important to validate the RPA classes. Methods and Materials: A total of 445 patients were randomized on RTOG 91-04, a Phase III study of accelerated hyperfractionation versus accelerated fractionation. No difference was observed between the two treatment arms with respect to survival. Four hundred thirty-two patients were included in this analysis. The majority of the patients were under age 65, had KPS 70-80, primary tumor controlled, and brain-only metastases. The initial RPA had three classes, but only patients in RPA Classes I and II were eligible for RTOG 91-04. Results: For RPA Class I, the median survival time was 6.2 months and 7.1 months for 91-04 and the database, respectively. The 1-year survival was 29% for 91-04 versus 32% for the database. There was no significant difference in the two survival distributions (p = 0.72). For RPA Class II, the median survival time was 3.8 months for 91-04 versus 4.2 months for the database. The 1-year survival was 12% and 16% for 91-04 and the database, respectively (p = 0.22). Conclusion: This analysis indicates that the RPA classes are valid and reliable for historical comparisons. Both the RTOG and other clinical trial organizers should currently utilize this RPA classification as a stratification factor for clinical trials

  20. Scanning usefulness for bone metastases diagnosis in the breast cancer follow-up

    International Nuclear Information System (INIS)

    Guillen, G.; Martinez, P.; Garcia, F.; Tres, A.

    1988-01-01

    It is studied the incidence of osseus metastases and the usefulness of 179 bone scanning realized in the diagnosis and follow-up (average: 23,6 months) of 87 patients operated by breast cancer. It is obvious the scan sensitivity and its unspecificity (15,08% phase-positives). In 13 (14,9%) patients who showed them, during the follow-up, scan was pathological at the moment of the osseus metastases diagnosis or a bit later; there were other clinical data or abnormal analytical ones of suspicion in 77% of them. The time average of appearance is 27 months after surgery. We concluded that the bone scan in the follow-up of breast cancer will be realized only when clinical or analytical suspicion of bone metastases. (Author)

  1. Whole Brain Radiotherapy With Hippocampal Avoidance and Simultaneous Integrated Boost for 1-3 Brain Metastases: A Feasibility Study Using Volumetric Modulated Arc Therapy

    International Nuclear Information System (INIS)

    Hsu, Fred; Carolan, Hannah; Nichol, Alan; Cao, Fred; Nuraney, Nimet; Lee, Richard; Gete, Ermias; Wong, Frances; Schmuland, Moira; Heran, Manraj; Otto, Karl

    2010-01-01

    Purpose: To evaluate the feasibility of using volumetric modulated arc therapy (VMAT) to deliver whole brain radiotherapy (WBRT) with hippocampal avoidance and a simultaneous integrated boost (SIB) for one to three brain metastases. Methods and Materials: Ten patients previously treated with stereotactic radiosurgery for one to three brain metastases underwent repeat planning using VMAT. The whole brain prescription dose was 32.25 Gy in 15 fractions, and SIB doses to brain metastases were 63 Gy to lesions ≥2.0 cm and 70.8 Gy to lesions 2 . Plans were optimized for conformity and target coverage while minimizing hippocampal and ocular doses. Plans were evaluated on target coverage, prescription isodose to target volume ratio, conformity number, homogeneity index, and maximum dose to prescription dose ratio. Results: Ten patients had 18 metastases. Mean values for the brain metastases were as follows: conformity number = 0.73 ± 0.10, target coverage = 0.98 ± 0.01, prescription isodose to target volume = 1.34 ± 0.19, maximum dose to prescription dose ratio = 1.09 ± 0.02, and homogeneity index = 0.07 ± 0.02. For the whole brain, the mean target coverage and homogeneity index were 0.960 ± 0.002 and 0.39 ± 0.06, respectively. The mean hippocampal dose was 5.23 ± 0.39 Gy 2 . The mean treatment delivery time was 3.6 min (range, 3.3-4.1 min). Conclusions: VMAT was able to achieve adequate whole brain coverage with conformal hippocampal avoidance and radiosurgical quality dose distributions for one to three brain metastases. The mean delivery time was under 4 min.

  2. Can the National Health Service Cancer Plan timeline be applied to colorectal hepatic metastases?

    LENUS (Irish Health Repository)

    Jones, Claire

    2012-02-01

    INTRODUCTION: The National Health Service (NHS) Cancer Plan guidelines recommend a maximum 2-week wait from referral to first appointment, and 2 months from referral to treatment for primary cancers. However, there are currently no guidelines available for metastatic disease. In the UK, nearly half of all colorectal cancer patients develop hepatic metastases. Timely, surgical resection offers the potential for cure. The aim of this study was to audit current practice for colorectal liver metastases in a regional hepatobiliary unit, and compare this to the NHS Cancer Plan standards for primary disease. PATIENTS AND METHODS: A retrospective review of the unit\\'s database was performed for all hepatic metastases referrals from January 2006 to December 2008. The dates of referral, first appointment, investigations and initiation of treatment, along with patient\\'s age and sex, were recorded on Microsoft Excel and analysed. Time was expressed as mean +\\/- SD in days. RESULTS: A total of 102 patients with hepatic metastases were identified. Five were excluded due to incomplete data. The average time from referral to first appointment was 10.6 +\\/- 9.4 days and the average time from referral to treatment was 38.5 +\\/- 28.6 days. Seventy-five (72.7%) had surgical intervention, of whom 37 also had chemotherapy. CONCLUSIONS: The data compare favourably to the NHS Cancer Plan guidelines for primary malignancy, demonstrating that a regional hepatobiliary unit is capable of delivering a service for colorectal liver metastases that adheres to the NHS Cancer Plan. Therefore, the NHS Cancer Plan can be applied to this cohort.

  3. Rare aggressive behavior of MDM2-amplified retroperitoneal dedifferentiated liposarcoma, with brain, lung and subcutaneous metastases

    Directory of Open Access Journals (Sweden)

    Imen Ben Salha

    2016-10-01

    Full Text Available Dedifferentiated liposarcoma (DDL is a histologically pleomorphic sarcoma, traditionally defined as well-differentiated liposarcoma with abrupt transition to high grade, nonlipogenic sarcoma. It can occur as part of recurrent well-differentiated liposarcoma, or may arise de novo. DDL most frequently occurs within the retroperitoneum, and while it is prone to local recurrence, it usually has a lower rate of metastasis than other pleomorphic sarcomas. We describe a case of retroperitoneal dedifferentiated liposarcoma in a 63-year-old male, who showed MDM2 amplification with fluorescence in situ hybridization, which displayed unusually aggressive behavior, with brain, lung and subcutaneous soft tissue metastases. As previous reports of metastatic liposarcoma have largely grouped DDL in with other (genetically and clinically distinct liposarcoma subtypes, we highlight and discuss the rare occurrence of brain metastasis in MDM2-amplified retroperitoneal liposarcoma.

  4. Risk of port-site metastases in pelvic cancers after robotic surgery.

    Science.gov (United States)

    Seror, J; Bats, A-S; Bensaïd, C; Douay-Hauser, N; Ngo, C; Lécuru, F

    2015-04-01

    To assess the risk of occurrence of port-site metastases after robotic surgery for pelvic cancer. Retrospective study from June 2007 to March 2013 of patients with gynecologic cancer who underwent robot-assisted surgery. We collected preoperative data, including characteristics of patients and FIGO stage, intraoperative data (surgery performed, number of ports), and postoperative data (occurrence of metastases, occurrence of port-site metastases). 115 patients were included in the study: 61 with endometrial cancer, 50 with cervical cancer and 4 with ovarian cancer. The surgical procedures performed were: hysterectomy with bilateral salpingo-oophorectomy, radical hysterectomy, pelvic lymphadenectomy, para-aortic lymphadenectomy and omentectomy. All surgical procedures required the introduction of 4 ports, 3 for the robot and 1 for the assistant. With a mean follow-up of 504.4 days (507.7 days for endometrial cancer, 479.5 days for cervical cancer, and 511.3 for ovarian cancer), we observed 9 recurrences but no port-site metastasis. No port-site metastasis has occurred in our series. However, larger, prospective and randomized works are needed to formally conclude. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. A randomised trial to compare cognitive outcome after gamma knife radiosurgery versus whole brain radiation therapy in patients with multiple brain metastases : Research protocol CAR-study B

    NARCIS (Netherlands)

    Schimmel, W.C.M.; Verhaak, E.; Hanssens, Patrick E. J.; Gehring, K.; Sitskoorn, M.M.

    2018-01-01

    Background Gamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is

  6. Radioimmune imaging of bone marrow in patients with suspected bone metastases from primary breast cancer

    International Nuclear Information System (INIS)

    Duncker, C.M.; Carrio, I.; Berna, L.; Estorch, M.; Alonso, C.; Ojeda, B.; Blanco, R.; Germa, J.R.; Ortega, V.

    1990-01-01

    Radioimmune imaging of bone marrow was performed by technetium-99m- (99mTc) labeled antigranulocyte monoclonal antibody BW 250/183 (AGMoAb) scans in 32 patients with suspected bone metastases from primary breast cancer. AGMoAb scans showed bone marrow defects in 25/32 (78%) patients; bone invasion was subsequently confirmed in 23 (72%) patients. Conventional bone scans performed within the same week detected bone metastases in 17/32 (53%) patients (p less than 0.001). AGMoAb scans detected more sites indicating metastatic disease than bone scans in 12 of these 17 patients (71%). All patients with bone metastases in the axial skeleton had bone marrow defects at least at the sites of bone metastases. Of 15 patients with normal, or indicative of, benign disease bone scans, 8 patients (53%) presented with bone marrow defects in the AGMoAb scans. Bone invasion was confirmed in six of them. AGMoAb bone marrow scans provide a method for the early detection of bone metastatic invasion in patients with breast cancer and suspected bone metastases

  7. Enhancing Quality of Life for Breast Cancer Patients with Bone Metastases

    Science.gov (United States)

    2008-04-01

    paclitaxel. British Journal of Cancer 84:1126-34; 2001. 46. Jilka, R. L., Weinstein , R. S., Bellido, T., Roberson, P., Parfitt, A. M., and Manolagas...D., and Harvey , W. J. Correlation of neoplasms with incidence and localization of skeletal metastases: An analysis of 1,355 diphosphonate bone scans

  8. Preventing surgery-induced NK cell dysfunction and cancer metastases with influenza vaccination

    Science.gov (United States)

    Tai, Lee-Hwa; Zhang, Jiqing; Auer, Rebecca C

    2013-01-01

    Surgical resection is the mainstay of treatment for solid tumors, but the postoperative period is uniquely inclined to the formation of metastases, largely due to the suppression of natural killer (NK) cells. We found that preoperative influenza vaccination prevents postoperative NK-cell dysfunction, attenuating tumor dissemination in murine models and promoting the activation of NK cells in cancer patients. PMID:24404430

  9. Zoledronic acid use in patients with bone metastases from renal cell carcinoma or bladder cancer.

    Science.gov (United States)

    Saad, Fred; Eastham, James A

    2010-06-01

    Approximately 30% of patients with renal cell carcinoma (RCC) and 40% of patients with bladder cancer develop bone metastases that can disrupt normal bone homeostasis and place patients at risk for potentially life-limiting skeletal-related events (SREs). In the absence of bone-directed therapies, patients with RCC may experience up to four SREs per year. In patients with bone metastases from RCC or bladder cancer, zoledronic acid (ZOL) significantly reduced the risk of SREs compared with placebo. In addition to its bone-protective effects, preclinical and early clinical evidence indicates that ZOL prevents tumor progression. For example, retrospective subset analysis in patients with RCC indicated that ZOL extended time to disease progression and demonstrated a trend toward improved overall survival compared with placebo. Additionally, a study in patients with bone metastases from bladder cancer demonstrated that ZOL improved 1-year overall survival compared with placebo. Bone metastases place a heavy burden on patients with RCC or bladder cancer, and early, continuous treatment with ZOL may provide anticancer benefits in addition to important patient quality of life. 2010. Published by Elsevier Inc.

  10. Prognostic Value of Estrogen Receptor alpha and Progesterone Receptor Conversion in Distant Breast Cancer Metastases

    NARCIS (Netherlands)

    Hoefnagel, Laurien D. C.; Moelans, Cathy B.; Meijer, S. L.; van Slooten, Henk-Jan; Wesseling, Pieter; Wesseling, Jelle; Westenend, Pieter J.; Bart, Joost; Seldenrijk, Cornelis A.; Nagtegaal, Iris D.; Oudejans, Joost; van der Valk, Paul; van Gils, Carla H.; van der Wall, Elsken; van Diest, Paul J.

    2012-01-01

    BACKGROUND: Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor alpha (ER alpha) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ER alpha and

  11. SU-E-T-536: LINAC-Based Single Isocenter Frameless SRT for Brain Metastases

    International Nuclear Inf