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Sample records for preventing brain metastases

  1. Profound prevention of experimental brain metastases of breast cancer by temozolomide in an MGMT-dependent manner

    PubMed Central

    Palmieri, Diane; Duchnowska, Renata; Woditschka, Stephan; Hua, Emily; Qian, Yongzhen; Biernat, Wojciech; Sosińska-Mielcarek, Katarzyna; Gril, Brunilde; Stark, Andreas; Hewitt, Stephen; Liewehr, David J; Steinberg, Seth M; Jassem, Jacek; Steeg, Patricia S

    2014-01-01

    Purpose Brain metastases of breast cancer cause neurocognitive damage and are incurable. We evaluated a role for temozolomide in the prevention of brain metastases of breast cancer in experimental brain metastasis models. Experimental Design Temozolomide was administered in mice following earlier injection of brain-tropic human epidermal growth factor receptor 2 (HER2)-positive Jimt1-BR3 and triple negative 231-BR-EGFP sublines, the latter with and without expression of 06-methylguanine-DNA methyltransferase (MGMT). Additionally, the percentage of MGMT-positive tumor cells in 62 patient-matched sets of breast cancer primary tumors and resected brain metastases was determined immunohistochemically. Results Temozolomide, when dosed at 50, 25, 10 or 5 mg/kg, 5 days/week, beginning 3 days after inoculation, completely prevented the formation of experimental brain metastases from MGMT-negative 231-BR-EGFP cells. At a 1 mg/kg dose, temozolomide prevented 68% of large brain metastases, and was ineffective at a dose of 0.5 mg/kg. When the 50 mg/kg dose was administered beginning on days 18 or 24, temozolomide efficacy was reduced or absent. Temozolomide was ineffective at preventing brain metastases in MGMT-transduced 231-BR-EGFP and MGMT-expressing Jimt-1-BR3 sublines. In 62 patient-matched sets of primary breast tumors and resected brain metastases, 43.5% of the specimens had concordant low MGMT expression, while in another 14.5% of sets high MGMT staining in the primary tumor corresponded with low staining in the brain metastasis. Conclusions Temozolomide profoundly prevented the outgrowth of experimental brain metastases of breast cancer in an MGMT-dependent manner. These data provide compelling rationale for investigating the preventive efficacy of temozolomide in a clinical setting. PMID:24634373

  2. MicroRNAs Linked to Trastuzumab Resistance, Brain Metastases | Division of Cancer Prevention

    Cancer.gov

    Researchers have tied increased levels of a microRNA (miRNA) to resistance to the targeted therapy trastuzumab (Herceptin) in women with HER2-positive breast cancer. Another research team has discovered a “signature” of miRNAs in brain metastases in patients with melanoma—a signature that is also present in the primary tumor and could identify melanoma patients at increased risk of brain metastases. |

  3. [Epidemiology of brain metastases].

    PubMed

    Taillibert, S; Le Rhun, É

    2015-02-01

    The most frequent intracranial brain tumours are brain metastases. All types of cancer can develop brain metastases but two thirds of brain metastases occurring in adult patients are secondary to one of these three cancers: lung cancer, breast cancer and melanoma. In accordance with these data, this review is focusing on the epidemiology of these three types of cancer. We report here the incidence, risk factors, median time of brain metastases occurrence after diagnosis of the primary cancer, prognosis and median survival for these three types of cancer. We also discuss the clinical implications of these data. The second part of this review is focusing on the Graded Prognostic Assessment scores in all types of primary cancer with brain metastases, how they can be applied in clinical research for a better stratification of patients, and to some extent in clinical practice to guide decisions for personalized treatments. These scores provide a better understanding of the different profiles of clinical evolution that can be observed amongst patients suffering from brain metastases according to the type of primary cancer. We highlighted the most remarkable and useful clinical implications of these data. PMID:25636729

  4. [Surgery of brain metastases].

    PubMed

    Métellus, P; Reyns, N; Voirin, J; Menei, P; Bauchet, L; Faillot, T; Loiseau, H; Pallud, J; Guyotat, J; Mandonnet, E

    2015-02-01

    Surgical excision of brain metastases has been well evaluated in unique metastases. Two randomized phase III trial have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful. Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, to rule out a differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system or radionecrosis). Finally, the biological documentation of brain metastatic disease might be useful in situations where a specific targeted therapy can be proposed. Selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved overall survival of cancer patients partially due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to the local treatment of brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients. PMID:25640217

  5. [Radiotherapy for brain metastases].

    PubMed

    Latorzeff, I; Antoni, D; Gaudaire-Josset, S; Feuvret, L; Tallet-Richard, A; Truc, G; Noël, G

    2016-09-01

    Radiotherapy for brain metastases has become more multifaceted. Indeed, with the improvement of the patient's life expectancy, side effects must be undeniably avoided and the retreatments or multiple treatments are common. The cognitive side effects should be warned and the most modern techniques of radiation therapy are used regularly to reach this goal. The new classifications of patients with brain metastases help guiding treatment more appropriately. Stereotactic radiotherapy has supplanted whole brain radiation therapy both for patients with metastases in place and for those who underwent surgery. Hippocampus protection is possible with intensity-modulated radiotherapy. Its relevance in terms of cognitive functioning should be more clearly demonstrated but the requirement, for using it, is increasingly strong. While addressing patients in palliative phase, the treatment of brain metastases is one of the localisations where technical thinking is the most challenging. PMID:27523410

  6. Future directions in treatment of brain metastases

    PubMed Central

    Barani, Igor J.; Larson, David A.; Berger, Mitchel S.

    2013-01-01

    Background: Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. Methods: A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. Results: The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Conclusions: Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT. PMID

  7. [Melanoma brain metastases : Treatment options].

    PubMed

    Rauschenberg, R; Tabatabai, G; Troost, E G C; Garzarolli, M; Beissert, S; Meier, F

    2016-07-01

    The majority of patients with metastatic melanoma will develop brain metastases, which are the most common cause of death. Until recently, local therapies (e. g., neurosurgery, radiotherapy) were the only options for brain metastases; however, effective systemic treatment options are now available. Upon suspicion of brain metastases, diagnostic staging with brain MRI and a neurological investigation are indicated. Prognostic factors such as number of cerebral metastases and symptoms, serum lactate dehydrogenase and S‑100 levels, extracerebral metastases, and ECOG status are considered during therapeutic planning. Treatment planning and therapeutic interventions should be based on an interdisciplinary and multimodal approach. Established treatments for singular brain metastases are neurosurgical resection and stereotactic radiotherapy, which can prolong survival. In patients with asymptomatic BRAF V600E-mutant brain metastases, the BRAF inhibitors dabrafenib, vemurafenib, and immunotherapy with ipilimumab are used. In the case of multiple symptomatic brain metastases, palliative whole-brain radiotherapy is used for treatment, although it has failed to show an overall survival benefit. Increased intracranial pressure and epileptic seizures are addressed with corticosteroids and anticonvulsants. Current clinical studies for melanoma patients with brain metastases are investigating new treatment options such as PD-1 antibodies, combined ipilimumab and nivolumab, combined BRAF inhibitors and MEK inhibitors, and stereotactic radiation in combination with immunotherapy or targeted therapy. PMID:27206449

  8. [Brain metastases imaging].

    PubMed

    Delmaire, C; Savatovsky, J; Boulanger, T; Dhermain, F; Le Rhun, E; Météllus, P; Gerber, S; Carsin-Nicole, B; Petyt, G

    2015-02-01

    The therapeutic management of brain metastases depends upon their diagnosis and characteristics. It is therefore imperative that imaging provides accurate diagnosis, identification, size and localization information of intracranial lesions in patients with presumed cerebral metastatic disease. MRI exhibits superior sensitivity to CT for small lesions identification and to evaluate their precise anatomical location. The CT-scan will be made only in case of MRI's contraindication or if MRI cannot be obtained in an acceptable delay for the management of the patient. In clinical practice, the radiologic metastasis evaluation is based on visual image analyses. Thus, a particular attention is paid to the imaging protocol with the aim to optimize the diagnosis of small lesions and to evaluate their evolution. The MRI protocol must include: 1) non-contrast T1, 2) diffusion, 3) T2* or susceptibility-weighted imaging, 4) dynamic susceptibility contrast perfusion, 5) FLAIR with contrast injection, 6) T1 with contrast injection preferentially using the 3D spin echo images. The role of the nuclear medicine imaging is still limited in the diagnosis of brain metastasis. The Tc-sestamibi brain imaging or PET with amino acid tracers can differentiate local brain metastasis recurrence from radionecrosis but still to be evaluated. PMID:25649387

  9. Brain metastases from ovarian carcinoma.

    PubMed

    Piura, Ettie; Piura, Benjamin

    2011-01-01

    This paper will focus on knowledge related to brain metastases from ovarian carcinoma. So far, less than 600 cases were documented in the literature with an incidence among ovarian carcinoma patients ranging from 0.29% to 11.6%. The ovarian carcinoma was usually an advanced-stage epithelial serous carcinoma, and the median interval between diagnosis of ovarian carcinoma and brain metastases was 2 years. Most often, brain metastases, affected the cerebrum, were multiple and part of a disseminated disease. Treatment of brain metastasis has evolved over the years from whole brain radiotherapy (WBRT) only to multimodal therapy including surgical resection or stereotactic radiosurgery followed by WBRT and/or chemotherapy. The median survival after diagnosis of brain metastases was 6 months; nevertheless, a significantly better survival was achieved with multimodal therapy compared to WBRT only. It is suggested that brain imaging studies should be included in the followup of patients after treatment for ovarian carcinoma. PMID:22191058

  10. [Stereotactic radiotherapy in brain metastases].

    PubMed

    Dhermain, F; Reyns, N; Colin, P; Métellus, P; Mornex, F; Noël, G

    2015-02-01

    Stereotactic radiotherapy of brain metastases is increasingly proposed after polydisciplinary debates among experts. Its definition and modalities of prescription, indications and clinical interest regarding the balance between efficacy versus toxicity need to be discussed. Stereotactic radiotherapy is a 'high precision' irradiation technique (within 1mm), using different machines (with invasive contention or frameless, photons X or gamma) delivering high doses (4 to 25Gy) in a limited number of fractions (usually 1 to 5, ten maximum) with a high dose gradient. Dose prescription will depend on materials, dose constraints to organs at risk varying with fractionation. Stereotactic radiotherapy may be proposed: (1) in combination with whole brain radiotherapy with the goal of increasing (modestly) overall survival of patients with a good performance status, 1 to 3 brain metastases and a controlled extracranial disease; (2) for recurrence of 1-3 brain metastases after whole brain radiotherapy; (3) after complete resection of a large and/or symptomatic brain metastases; (4) after diagnosis of 3-5 asymptomatic new or progressing brain metastases during systemic therapy, with the aim of delaying whole brain radiotherapy (avoiding its potential neurotoxicity) and maintaining a high focal control rate. Only a strict follow-up with clinical and MRI every 3 months will permit to deliver iterative stereotactic radiotherapies without jeopardizing survival. Simultaneous delivering of stereotactic radiotherapy with targeted medicines should be carefully discussed. PMID:25640215

  11. Brain metastases from endometrial carcinoma.

    PubMed

    Piura, Ettie; Piura, Benjamin

    2012-01-01

    This paper will focus on knowledge related to brain metastases from endometrial carcinoma. To date, 115 cases were documented in the literature with an incidence of 0.6% among endometrial carcinoma patients. The endometrial carcinoma was usually an advanced-stage and high-grade tumor. In most patients (~90%), brain metastasis was detected after diagnosis of endometrial carcinoma with a median interval from diagnosis of endometrial carcinoma to diagnosis of brain metastases of 17 months. Brain metastasis from endometrial carcinoma was either an isolated disease limited to the brain only (~50%) or part of a disseminated disease involving also other parts of the body (~50%). Most often, brain metastasis from endometrial carcinoma affected the cerebrum (~75%) and was solitary (~60%). The median survival after diagnosis of brain metastases from endometrial carcinoma was 5 months; however, a significantly better survival was achieved with multimodal therapy including surgical resection or stereotactic radiosurgery followed by whole brain radiotherapy (WBRT) and/or chemotherapy compared to WBRT alone. It is suggested that brain imaging studies should be considered in the routine follow up of patients with endometrial carcinoma and that the search for a primary source in females with brain metastases of unknown primary should include endometrial biopsy. PMID:22523707

  12. Stereotactic radiosurgery of brain metastases.

    PubMed

    Specht, Hanno M; Combs, Stephanie E

    2016-09-01

    Brain metastases are a common problem in solid malignancies and still represent a major cause of morbidity and mortality. With the ongoing improvement in systemic therapies, the expectations on the efficacy of brain metastases directed treatment options are growing. As local therapies against brain metastases continue to evolve, treatment patterns have shifted from a palliative "one-treatment-fits-all" towards an individualized, patient adapted approach. In this article we review the evidence for stereotactic radiation treatment based on the current literature. Stereotactic radiosurgery (SRS) as a local high precision approach for the primary treatment of asymptomatic brain metastases has gained wide acceptance. It leads to lasting tumor control with only minor side effects compared to whole brain radiotherapy, since there is only little dose delivered to the healthy brain. The same holds true for hypofractionated stereotactic radiotherapy (HFSRT) for large metastases or for lesions close to organs at risk (e.g. the brainstem). New treatment indications such as neoadjuvant SRS followed by surgical resection or postoperative local therapy to the resection cavity show promising data and are also highlighted in this manuscript. With the evolution of local treatment options, optimal patient selection becomes more and more crucial. This article aims to aid decision making by outlining prognostic factors, treatment techniques and indications and common dose prescriptions. PMID:27071010

  13. Brain metastases of breast cancer.

    PubMed

    Palmieri, Diane; Smith, Quentin R; Lockman, Paul R; Bronder, Julie; Gril, Brunilde; Chambers, Ann F; Weil, Robert J; Steeg, Patricia S

    Central nervous system or brain metastases traditionally occur in 10-16% of metastatic breast cancer patients and are associated with a dismal prognosis. The development of brain metastases has been associated with young age, and tumors that are estrogen receptor negative, Her-2+ or of the basal phenotype. Treatment typically includes whole brain irradiation, or either stereotactic radiosurgery or surgery with whole brain radiation, resulting in an approximately 20% one year survival. The blood-brain barrier is a formidable obstacle to the delivery of chemotherapeutics to the brain. Mouse experimental metastasis model systems have been developed for brain metastasis using selected sublines of human MDA-MB-231 breast carcinoma cells. Using micron sized iron particles and MRI imaging, the fate of MDA-MB-231BR cells has been mapped: Approximately 2% of injected cells form larger macroscopic metastases, while 5% of cells remain as dormant cells in the brain. New therapies with permeability for the blood-brain barrier are needed to counteract both types of tumor cells. PMID:17473372

  14. Radiosurgery for Large Brain Metastases

    SciTech Connect

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

    2012-05-01

    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{sup 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{sup 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{sup 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.

  15. Comparing Postoperative Radiation Therapies for Brain Metastases

    Cancer.gov

    In this clinical trial, patients with one to four brain metastases who have had at least one of the metastatic tumors removed surgically will be randomly assigned to undergo whole-brain radiation therapy or stereotactic radiosurgery.

  16. Radiosurgery for brain metastases and cerebral edema.

    PubMed

    Gazit, Inbal; Har-Nof, Sagi; Cohen, Zvi R; Zibly, Zion; Nissim, Uzi; Spiegelmann, Roberto

    2015-03-01

    The objective of this study was to assess reduction in cerebral edema following linear accelerator radiosurgery (LINAC) as first line therapy for brain metastasis. We reviewed the medical records of all patients who underwent LINAC radiosurgery for brain metastasis at our institution during 2010-2012, and who had not previously undergone either surgery or whole brain radiotherapy. Data were analyzed for 55 brain metastases from 46 patients (24 males), mean age 59.9 years. During the 2 months following LINAC radiosurgery, the mean steroid dose decreased from 4.8 to 2.6 mg/day, the mean metastasis volume decreased from 3.79±4.12 cc to 2.8±4.48 cc (p=0.001), and the mean edema volume decreased from 16.91±30.15 cc to 12.85±24.47 cc (p=0.23). The 17 patients with reductions of more than 50% in brain edema volume had single metastases. Edema volume in the nine patients with two brain metastases remained stable in five patients (volume change <10%, 0-2 cc) and increased in four patients (by >10%, 2-14 cc). In a subanalysis of eight metastases with baseline edema volume greater than 40 cc, edema volume decreased from 77.27±37.21 cc to 24.84±35.6 cc (p=0.034). Reductions in brain edema were greater in metastases for which non-small-cell lung carcinoma and breast cancers were the primary diseases. Overall, symptoms improved in most patients. No patients who were without symptoms or who had no signs of increased intracranial pressure at baseline developed signs of intracranial pressure following LINAC radiosurgery. In this series, LINAC stereotactic radiosurgery for metastatic brain lesions resulted in early reduction in brain edema volume in single metastasis patients and those with large edema volumes, and reduced the need for steroids. PMID:25533053

  17. [Systemic treatment of melanoma brain metastases].

    PubMed

    Le Rhun, É; Mateus, C; Mortier, L; Dhermain, F; Guillot, B; Grob, J-J; Lebbe, C; Thomas, M; Jouary, T; Leccia, M-T; Robert, C

    2015-02-01

    Melanomas have a high rate of brain metastases. Both the functional prognosis and the overall survival are poor in these patients. Until now, surgery and radiotherapy represented the two main modalities of treatment. Nevertheless, due to the improvement in the management of the extracerebral melanoma, the systemic treatment may be an option in patients with brain metastases. Immunotherapy with anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) - ipilimumab - or BRAF (serine/threonine-protein kinase B-raf) inhibitors - vemurafenib, dabrafenib - has shown efficacy in the management of brain metastases in a- or pauci-symptomatic patients. Studies are ongoing with anti-PD1 (programmed cell death 1) and combinations of targeted therapies associating anti-RAF (raf proto-oncogene, serine/threonine kinase) and anti-MEK (mitogen-activated protein kinase kinase). PMID:25656856

  18. The Blood-Brain Barrier Challenge for the Treatment of Brain Cancer, Secondary Brain Metastases, and Neurological Diseases.

    PubMed

    Weidle, Ulrich H; Niewöhner, Jens; Tiefenthaler, Georg

    2015-01-01

    Formation of metastases from various tumor entities in the brain is a major problem for the treatment of advanced cancer. We describe target molecules and tools for the delivery of small molecules or proteins across the blood-brain barrier (BBB), and the treatment of brain tumors and metastases with antibody-related moieties. In addition, drugs preventing formation of metastases or interfering with the growth of established metastases are described, as well as pre-clinical metastasis models and corresponding clinical data. Furthermore, we discuss the delivery of effector proteins and antibody-based moieties fused with an antibody-based scaffold across the BBB in several model systems which might be applicable for the treatment of brain metastases. PMID:26136217

  19. [Mangement of brain metastases based on EBM].

    PubMed

    Narita, Yoshitaka

    2005-04-01

    Some three hundred thousand of patients die of cancers yearly and at least 20-40%, i. e., 60,000-120,000 of them suffered from brain metastases. Those with such metastases have a generally poor outcome with a median survival of 1-2 months with steroids only, and approximately 6 months with whole-brain radiation therapy (WBRT). The results of important and historical clinical trials including surgery, WBRT, stereotactic radiosurgery (SRS), and chemotherapy are reviewed. Surgery with WBRT has been used in the treatment of a single brain metatasis with a diameter of more than 3 cm, while survival time of those patients is approximately 12 months. SRS including gamma knife is widely used for treatment of small and multiple brain metastases. However, many clinical studies have revealed that SRS+WBRT is superior to WBRT or SRS alone in survival time and local control rates. The accurate incident rates of radiation-induced dementia or neurological deficit are still unclear, so the problem and possible avoidance of an additional WBRT after surgery or SRS are discussed. To improve neurologic function and survival, the treatment for patients with brain metastases should be selected with accurate knowledge of EBM. PMID:15853211

  20. Updates in the management of brain metastases.

    PubMed

    Arvold, Nils D; Lee, Eudocia Q; Mehta, Minesh P; Margolin, Kim; Alexander, Brian M; Lin, Nancy U; Anders, Carey K; Soffietti, Riccardo; Camidge, D Ross; Vogelbaum, Michael A; Dunn, Ian F; Wen, Patrick Y

    2016-08-01

    The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survival, associated with increased time at risk for developing BM. Development of systemic therapies capable of preventing BM and controlling both intracranial and extracranial disease once BM are diagnosed is paramount. The increase in use of stereotactic radiosurgery alone for many patients with multiple BM is an outgrowth of the desire to employ treatments focused on local control while minimizing cognitive effects associated with whole brain radiotherapy. Complications from BM and their treatment must be considered in comprehensive patient management, especially with greater awareness that the majority of patients do not die from their BM. Being aware of significant heterogeneity in prognosis and therapeutic options for patients with BM is crucial for appropriate management, with greater attention to developing individual patient treatment plans based on predicted outcomes; in this context, recent prognostic models of survival have been extensively revised to incorporate molecular markers unique to different primary cancers. PMID:27382120

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25846288

  2. Evolving treatment options for melanoma brain metastases.

    PubMed

    Ajithkumar, Thankamma; Parkinson, Christine; Fife, Kate; Corrie, Pippa; Jefferies, Sarah

    2015-10-01

    Melanoma is a leading cause of lost productivity due to premature cancer mortality. Melanoma frequently spreads to the brain and is associated with rapid deterioration in quality and quantity of life. Until now, treatment options have been restricted to surgery and radiotherapy, although neither modality has been well studied in clinical trials. However, the new immune checkpoint inhibitors and molecularly targeted agents that have been introduced for treatment of metastatic melanoma are active against brain metastases and offer new opportunities to improve disease outcomes. New challenges arise, including how to integrate or sequence multiple treatment modalities, and current practice varies widely. In this Review, we summarise evidence for the treatment of melanoma brain metastases, and discuss the rationale and evidence for combination modalities, highlighting areas for future research. PMID:26433822

  3. Peritoneal Metastases: Prevention and Treatment.

    PubMed

    Sugarbaker, Paul H

    2016-06-01

    Colorectal cancer is a surgicaly curable disease. It requires multimodality of treatment in Localy advanced and metastatic disease. Molecular markers like RAS mutation has brought in change in the mangement of metastatic disease. Nearly 15 to 20 % presents with peritonieal surface metastasis. The debate continues with systomic vs Cyutoreductive surgery with are without HIPEC. This article highlights management of peritoneal metastasis with special reference to prevention and treatment. PMID:27065703

  4. Radiotherapy: Neurocognitive considerations in the treatment of brain metastases.

    PubMed

    Marko, Nicholas F; Weil, Robert J

    2010-04-01

    The results of a randomized, controlled trial investigating the neurocognitive effects of stereotactic radiosurgery (SRS), with or without whole-brain radiation therapy (WBRT), to treat brain metastases demonstrated a significant reduction in learning and memory, associated with the addition of WBRT to SRS. the results indicate that SRS monotherapy is an effective and safe initial management strategy for brain metastases. PMID:20354539

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

    SciTech Connect

    Lester, Jason Francis . E-mail: jason.lester@velindre-tr.wales.nhs.uk; MacBeth, Fergus R.; Coles, Bernadette

    2005-11-01

    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.

  6. Incipient Melanoma Brain Metastases Instigate Astrogliosis and Neuroinflammation.

    PubMed

    Schwartz, Hila; Blacher, Eran; Amer, Malak; Livneh, Nir; Abramovitz, Lilach; Klein, Anat; Ben-Shushan, Dikla; Soffer, Shelly; Blazquez, Raquel; Barrantes-Freer, Alonso; Müller, Meike; Müller-Decker, Karin; Stein, Reuven; Tsarfaty, Galia; Satchi-Fainaro, Ronit; Umansky, Viktor; Pukrop, Tobias; Erez, Neta

    2016-08-01

    Malignant melanoma is the deadliest of skin cancers. Melanoma frequently metastasizes to the brain, resulting in dismal survival. Nevertheless, mechanisms that govern early metastatic growth and the interactions of disseminated metastatic cells with the brain microenvironment are largely unknown. To study the hallmarks of brain metastatic niche formation, we established a transplantable model of spontaneous melanoma brain metastasis in immunocompetent mice and developed molecular tools for quantitative detection of brain micrometastases. Here we demonstrate that micrometastases are associated with instigation of astrogliosis, neuroinflammation, and hyperpermeability of the blood-brain barrier. Furthermore, we show a functional role for astrocytes in facilitating initial growth of melanoma cells. Our findings suggest that astrogliosis, physiologically instigated as a brain tissue damage response, is hijacked by tumor cells to support metastatic growth. Studying spontaneous melanoma brain metastasis in a clinically relevant setting is the key to developing therapeutic approaches that may prevent brain metastatic relapse. Cancer Res; 76(15); 4359-71. ©2016 AACR. PMID:27261506

  7. Stereotactic radiosurgery and stereotactic radiotherapy for brain metastases.

    PubMed

    Halasz, Lia M; Rockhill, Jason K

    2013-01-01

    Stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HFSRT) have become important treatment modalities for brain metastases. While effective, there are still areas of extensive debate on its appropriate use in patients with life-limiting diseases. This review provides an overview of the indications and challenges of SRS and HFSRT in the management of brain metastases. PMID:23717789

  8. Immune Checkpoint Inhibitors in Brain Metastases: From Biology to Treatment.

    PubMed

    Berghoff, Anna S; Venur, Vyshak A; Preusser, Matthias; Ahluwalia, Manmeet S

    2016-01-01

    Cancer immunotherapy has been a subject of intense research over the last several years, leading to new approaches for modulation of the immune system to treat malignancies. Immune checkpoint inhibitors (anti-CLTA-4 antibodies and anti-PD-1/PD-L1 antibodies) potentiate the host's own antitumor immune response. These immune checkpoint inhibitors have shown impressive clinical efficacy in advanced melanoma, metastatic kidney cancer, and metastatic non-small cell lung cancer (NSCLC)-all malignancies that frequently cause brain metastases. The immune response in the brain is highly regulated, challenging the treatment of brain metastases with immune-modulatory therapies. The immune microenvironment in brain metastases is active with a high density of tumor-infiltrating lymphocytes in certain patients and, therefore, may serve as a potential treatment target. However, clinical data of the efficacy of immune checkpoint inhibitors in brain metastases compared with extracranial metastases are limited, as most clinical trials with these new agents excluded patients with active brain metastases. In this article, we review the current scientific evidence of brain metastases biology with specific emphasis on inflammatory tumor microenvironment and the evolving state of clinical application of immune checkpoint inhibitors for patients with brain metastases. PMID:27249713

  9. Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature.

    PubMed

    Piura, E; Piura, B

    2014-01-01

    Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months. PMID:25118474

  10. GE-20GENOMIC CHARACTERIZATION OF BREAST CANCER BRAIN METASTASES

    PubMed Central

    Michelhaugh, Sharon; Bollig-Fischer, Aliccia; Alosh, Baraa; Ali-Fehmi, Rouba; Mittal, Sandeep

    2014-01-01

    BACKGROUND: The incidence of central nervous system metastasis from primary breast cancer has steadily increased with introduction of more effective molecular-targeted therapies resulting in improved long-term survival. Current standard-of-care treatment modalities for CNS metastases include microsurgical resection, whole-brain radiation therapy, and stereotactic radiosurgery, either alone or in combination. There are currently no FDA-approved drugs with an indication for breast cancer brain metastases. Clearly, there is a dire need to identify biomarkers permitting earlier and accurate diagnosis of CNS metastases, development of prevention strategies in high-risk individuals, and establishing more effective treatment options such as targeted systemic and intrathecal therapies. METHODS: Extracted DNA from metastatic brain tumors (MBTs) and matched tissues from primary breast tumors was quantified and array comparative genomic hybridizations (aCGH) were performed with Agilent SurePrint arrays (G3 ISCA CGH + SNP 180K) using a commercially-available, genetically-normal female DNA standard. Bioinformatics analysis was performed using Agilent CytoGenomics Edition 2.5.8.1. Data were filtered against the Cancer Gene Census (Wellcome Trust Sanger Institute) to identify genes with well-characterized roles in cancer. RESULTS: From genomic copy number data analysis tailored to uncover the most frequent gene aberrations in breast cancer MBTs, we identified that MYC oncogene amplification was among the most common. Pathway analysis of the analyzed gene set of recurring gene aberrations identified the Human Embryonic Stem Cell Pluripotency pathway as being over-represented. The genes in this pathway showing copy number gain include NTRK1, PIK3CA and SOX2. Direct comparisons of MBTs with their matched primary tumor (n = 4) revealed a range of examples for highly similar and divergent patterns of gene aberrations. In one case ERBB2 was confirmed to be in the MBT, and not in the

  11. Brain metastases from cervical carcinoma: overview of pertinent literature.

    PubMed

    Piura, E; Piura, B

    2012-01-01

    Brain metastasis from cervical carcinoma is rare with only about 100 cases documented in the literature and an incidence among cervical carcinoma patients of 0.6%. The median interval between diagnosis of cervical carcinoma and brain metastases is 18 months. The brain can be the only site of distant metastasis of cervical carcinoma ("isolated brain metastases") (46.8%) or brain metastasis can be part of a disseminated cervical carcinoma involving also other sites of the body (53.2%). Brain metastasis of cervical carcinoma affects most often the cerebrum (73%) and can be either single (one metastasis) (50.6%) or multiple (> or = two metastases) (49.4%). Treatment of brain metastases has evolved over the years from whole brain radiotherapy (WBRT) alone to multimodal therapy including surgical resection (craniotomy) or stereotactic radiosurgery (SRS) followed by WBRT +/- chemotherapy. The median overall survival after diagnosis of brain metastases is four months; however, a better survival is achieved with multimodal therapy (craniotomy followed by WBRT) compared to craniotomy alone or WBRT alone. The worst survival is observed in patients with no treatment. Although based on a very small number of patients, the best survival is noticed in patients having SRS either alone or in combination with other treatment modality. PMID:23327047

  12. [Systemic treatment of brain metastases from breast cancer].

    PubMed

    Taillibert, S; Conforti, R; Bonneterre, J; Bachelot, T; Le Rhun, E; Bernard-Marty, C

    2015-02-01

    An increase in the incidence of breast cancer patients with brain metastases has been observed over the last years, mainly because the recent development of new drugs including therapies targeting HER2 (human epidermal growth factor receptor 2) resulted in an increased survival of these patients. With HER2+ patients living longer and the well-known neurotropism of HER2+ tumour cells, the resulting high incidence of brain metastases is not really surprising. Moreover, brain metastases more often occur within a context of existing extracranial metastases. These need to be treated at the same time in order to favourably impact patients' survival. Consequently, the management of breast cancer patients with brain metastases clearly relies on a multidisciplinary approach, including systemic treatment. A working group including neuro-oncologists, neurosurgeons, radiation oncologists and oncologists was created in order to provide French national guidelines for the management of brain metastases within the "Association des neuro-oncologues d'expression française" (ANOCEF). The recommendations regarding the systemic treatment in breast cancer patients are reported here including key features of their management. PMID:25662600

  13. [ANOCEF guidelines for the management of brain metastases].

    PubMed

    Le Rhun, É; Dhermain, F; Noël, G; Reyns, N; Carpentier, A; Mandonnet, E; Taillibert, S; Metellus, P

    2015-02-01

    The incidence of brain metastases is increasing because of the use of new therapeutic agents, which allow an improvement of overall survival, but with only a poor penetration into the central nervous system brain barriers. The management of brain metastases has changed due to a better knowledge of immunohistochemical data and molecular biological data, the development of new surgical, radiotherapeutic approaches and improvement of systemic treatments. Most of the time, the prognosis is still limited to several months, nevertheless, prolonged survival may be now observed in some sub-groups of patients. The main prognostic factors include the type and subtype of the primitive, age, general status of the patient, number and location of brain metastases, extracerebral disease. The multidisciplinary discussion should take into account all of these parameters. We should notice also that treatments including surgery or radiotherapy may be proposed in a symptomatic goal in advanced phases of the disease underlying the multidisciplinary approach until late in the evolution of the disease. This article reports on the ANOCEF (French neuro-oncology association) guidelines. The management of brain metastases of breast cancers and lung cancers are discussed in the same chapter, while the management of melanoma brain metastases is reported in a separate chapter due to different responses to the brain radiotherapy. PMID:25666314

  14. Outcomes After Whole Brain Reirradiation in Patients With Brain Metastases

    SciTech Connect

    Son, Christina H.; Jimenez, Rachel; Niemierko, Andrzej; Loeffler, Jay S.; Oh, Kevin S.; Shih, Helen A.

    2012-02-01

    Purpose: Patients with brain metastases are often treated with whole brain radiation therapy (WBRT) for purposes of palliation. The treatment of those who experience subsequent intracranial disease progression can include a second course of WBRT, although there is controversy surrounding its safety and efficacy. This study examines the outcomes in patients at Massachusetts General Hospital who underwent reirradiation. Patients and Methods: We examined the medical records of 17 patients at Massachusetts General Hospital with brain metastases who were initially treated with WBRT between 2002 and 2008 and were subsequently retreated with a second course of WBRT. The median dose for the first course of WBRT was 35 Gy (range, 28-40 Gy), with a fraction size of 2 to 3 Gy (median, 2.5 Gy). The median dose at reirradiation was 21.6 Gy (range, 14-30 Gy), with a fraction size of 1.5 to 2 Gy (median, 1.8 Gy). Results: The second course of WBRT was administered upon radiographic disease progression in all patients. Of 10 patients with complete follow-up data, 8 patients experienced complete or partial symptom resolution, and 2 did not show clinical improvement. The time to radiographic progression was 5.2 months. The median overall survival for all patients after diagnosis of metastases was 24.7 months. The median survival time after initiation of reirradiation was 5.2 months (95% CI, 1.3-8.7). In 6 patients with stable extracranial disease, the median survival time after retreatment was 19.8 months (95% CI, 2.7-{infinity}), compared with 2.5 months (95% CI, 0.8-5.5) for those with extracranial disease progression (p = 0.05). Acute adverse reactions occurred in 70.5% of patients but were mild to moderate in severity. Conclusion: In select patients and especially those with stable extracranial disease, reirradiation may be an appropriate and effective intervention to provide symptomatic relief and slow intracranial disease progression. Side effects were minimal and did not

  15. [Complex treatment of breast cancer patients with brain metastases].

    PubMed

    Medvedev, S V; Tkachev, S I; Moskvina, E A; Mikhina, Z P; Naskhletashvili, D R; Bulychkin, P V; Romanov, D S; Trofimova, O P; Berdnik, A V; Bykova, Yu B; Gutnik, R A; Yazhgunovich, I P; Fedoseenko, D I

    2015-01-01

    Brain metastases in breast cancer develop for 24-32 months after the detection of the primary tumor. The study included patients with brain metastases who were divided into three groups: the first group--with early chemoradiotherapy (CRT) without induction chemotherapy (IC) by capecitabine; the second group--with delayed CRT with 4 or 8 courses of IC by capecitabine; the third group (a historical control) who received only whole brain radiation therapy. The median time to progression of intracranial metastases was 15.3, 12 and 5 months, respectively. The median time to the intracranial progression significantly less in the third group (5 months) compared with the first (15.3 months) (p = 0.0007) and the second (12 months) (p = 0.027) groups. The overall survival rate was 22.1, 15.1 and 6.8 months in three groups, respectively. PMID:26995988

  16. Novel treatment strategies for brain tumors and metastases

    PubMed Central

    El-Habashy, Salma E.; Nazief, Alaa M.; Adkins, Chris E.; Wen, Ming Ming; El-Kamel, Amal H.; Hamdan, Ahmed M.; Hanafy, Amira S.; Terrell, Tori O.; Mohammad, Afroz S.; Lockman, Paul R.; Nounou, Mohamed Ismail

    2015-01-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood–brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

  17. Novel treatment strategies for brain tumors and metastases.

    PubMed

    El-Habashy, Salma E; Nazief, Alaa M; Adkins, Chris E; Wen, Ming Ming; El-Kamel, Amal H; Hamdan, Ahmed M; Hanafy, Amira S; Terrell, Tori O; Mohammad, Afroz S; Lockman, Paul R; Nounou, Mohamed Ismail

    2014-05-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood-brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

  18. Prevention and Treatment of Bone Metastases in Breast Cancer

    PubMed Central

    Carla, Ripamonti; Fabio, Trippa; Gloria, Barone; Ernesto, Maranzano

    2013-01-01

    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. PMID:26237068

  19. Molecular MRI enables early and sensitive detection of brain metastases.

    PubMed

    Serres, Sébastien; Soto, Manuel Sarmiento; Hamilton, Alastair; McAteer, Martina A; Carbonell, W Shawn; Robson, Matthew D; Ansorge, Olaf; Khrapitchev, Alexandre; Bristow, Claire; Balathasan, Lukxmi; Weissensteiner, Thomas; Anthony, Daniel C; Choudhury, Robin P; Muschel, Ruth J; Sibson, Nicola R

    2012-04-24

    Metastasis to the brain is a leading cause of cancer mortality. The current diagnostic method of gadolinium-enhanced MRI is sensitive only to larger tumors, when therapeutic options are limited. Earlier detection of brain metastases is critical for improved treatment. We have developed a targeted MRI contrast agent based on microparticles of iron oxide that enables imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Our objectives here were to determine whether VCAM-1 is up-regulated on vessels associated with brain metastases, and if so, whether VCAM-1-targeted MRI enables early detection of these tumors. Early up-regulation of cerebrovascular VCAM-1 expression was evident on tumor-associated vessels in two separate murine models of brain metastasis. Metastases were detectable in vivo using VCAM-1-targeted MRI 5 d after induction (<1,000 cells). At clinical imaging resolutions, this finding is likely to translate to detection at tumor volumes two to three orders of magnitude smaller (0.3-3 × 10(5) cells) than those volumes detectable clinically (10(7)-10(8) cells). VCAM-1 expression detected by MRI increased significantly (P < 0.0001) with tumor progression, and tumors showed no gadolinium enhancement. Importantly, expression of VCAM-1 was shown in human brain tissue containing both established metastases and micrometastases. Translation of this approach to the clinic could increase therapeutic options and change clinical management in a substantial number of cancer patients. PMID:22451897

  20. Molecular MRI enables early and sensitive detection of brain metastases

    PubMed Central

    Serres, Sébastien; Soto, Manuel Sarmiento; Hamilton, Alastair; McAteer, Martina A.; Carbonell, W. Shawn; Robson, Matthew D.; Ansorge, Olaf; Khrapitchev, Alexandre; Bristow, Claire; Balathasan, Lukxmi; Weissensteiner, Thomas; Anthony, Daniel C.; Choudhury, Robin P.; Muschel, Ruth J.; Sibson, Nicola R.

    2012-01-01

    Metastasis to the brain is a leading cause of cancer mortality. The current diagnostic method of gadolinium-enhanced MRI is sensitive only to larger tumors, when therapeutic options are limited. Earlier detection of brain metastases is critical for improved treatment. We have developed a targeted MRI contrast agent based on microparticles of iron oxide that enables imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Our objectives here were to determine whether VCAM-1 is up-regulated on vessels associated with brain metastases, and if so, whether VCAM-1–targeted MRI enables early detection of these tumors. Early up-regulation of cerebrovascular VCAM-1 expression was evident on tumor-associated vessels in two separate murine models of brain metastasis. Metastases were detectable in vivo using VCAM-1–targeted MRI 5 d after induction (<1,000 cells). At clinical imaging resolutions, this finding is likely to translate to detection at tumor volumes two to three orders of magnitude smaller (0.3–3 × 105 cells) than those volumes detectable clinically (107–108 cells). VCAM-1 expression detected by MRI increased significantly (P < 0.0001) with tumor progression, and tumors showed no gadolinium enhancement. Importantly, expression of VCAM-1 was shown in human brain tissue containing both established metastases and micrometastases. Translation of this approach to the clinic could increase therapeutic options and change clinical management in a substantial number of cancer patients. PMID:22451897

  1. Brain metastases in metastatic non-small cell lung cancer responding to single-agent gefitinib: a case report.

    PubMed

    Stemmler, H J; Weigert, O; Krych, M; Schoenberg, S O; Ostermann, H; Hiddemann, W

    2005-08-01

    Brain metastases are a frequent finding in patients with non-small cell lung cancer (NSCLC). The present case reports the clinical course of a patient who was treated with gefitinib alone for progressive brain metastases after whole-brain irradiation treatment (WBRT). A 50-year-old women with primary stage IV NSCLC (bone metastases) developed brain metastases after 3 cycles of chemotherapy consisting of paclitaxel and carboplatin (CBDA). After completion of the WBRT, magnetic resonance imaging (MRI) indicated further progression. Two cycles of temozolomide and topotecan were applied; this was ineffective in preventing central nervous system progression. For symptomatic brain metastatic disease the patient received gefitinib as single-agent treatment. Within a few weeks of treatment there was an obvious clinical improvement. Follow-up of the brain 2 months after the start of treatment showed a decrease in both the size and number of brain metastases. Additional manifestations in the lungs and the skeletal system were re-assessed as stable disease during the treatment with gefitinib. Within 4 months of treatment there were no side-effects such as skin rash or any other systemic toxicity. Gefitinib may therefore have a role in the treatment of brain metastases from NSCLC. PMID:16027524

  2. Symptoms and Quality of Life in Cancer Patients With Brain Metastases Following Palliative Radiotherapy

    SciTech Connect

    Wong, Jennifer; Hird, Amanda; Zhang Liying; Tsao, May; Sinclair, Emily; Barnes, Elizabeth; Danjoux, Cyril; Chow, Edward

    2009-11-15

    Purpose: To examine prospectively patient self-rated symptoms and quality of life (QOL) indicators in patients with brain metastases following whole brain radiotherapy (WBRT). Methods and Materials: Consecutive patients with brain metastases referred for WBRT were approached for this study. Patients were asked to rate their symptoms and QOL using the Spitzer Quality of Life Index questionnaire. Follow-up was at 1, 2, and 3 months following WBRT. Linear regression analysis was used to determine the change in symptom severity over time. Results: Between August 2005 to October 2007, 129 patients with brain metastases were enrolled. The majority of patients (88%) received 20 Gy in five fractions. Median age was 64 years, and median Karnofsky Performance Status at baseline was 70. The most commonly experienced symptoms at baseline were headaches, weakness, balance problems, and fatigue. Thirty-five percent of patients rated neurological functional (NF) status as 1, indicating moderate neurological symptoms and need for assistance. Forty-three percent of patients had stable or decreased fatigue, and 47% had a stable or improved NF status over time (p = 0.0040). Although certain QOL domains improved over time, all other QOL domains and symptom items did not change significantly following WBRT. Conclusion: WBRT may have contributed to symptom stabilization in our study. An alternative goal of WBRT may be the prevention of symptom progression and QOL deterioration. Further research is required to select the most appropriate group of patients with brain metastases who would benefit most from WBRT.

  3. Ipilimumab and whole brain radiation therapy for melanoma brain metastases

    PubMed Central

    Gerber, Naamit K.; Young, Robert J.; Barker, Christopher A.; Wolchok, Jedd D.; Chan, Timothy A.; Yamada, Yoshiya; Friguglietti, Leigh

    2016-01-01

    Brain metastases (BM) frequently develop in patients with melanoma and are associated with a poor prognosis. Whole brain radiation therapy (WBRT) is a standard intervention for intracranial disease, particularly in patients with multiple BM. Ipilimumab improves survival in patients with advanced melanoma. The purpose of this study is to investigate the safety and efficacy of concurrent WBRT and ipilimumab. A retrospective analysis was conducted of 13 consecutive patients treated with WBRT within 30 days of ipilimumab administration. Radiographic response, as measured by serial magnetic resonance imaging scans post-treatment, was graded by modified World Health Organization (mWHO) and immune-related response criteria (irRC) in the 9 patients with follow-up imaging. Treatment-related toxicity was prospectively assessed during treatment. Four of nine patients (44 %) experienced partial response or stable central nervous system (CNS) disease as measured by mWHO criteria. This number increased to 5 patients (56 %) when irRC criteria were used. Rates of treatment-related neurologic toxicity were low with only one patient experiencing grade 3–4 neurologic toxicity. There was a high rate of intratumoral hemorrhage in this patient population, with 10 of 10 patients with post-treatment imaging demonstrating new or increased intratumoral bleeding after WBRT. This retrospective study demonstrates that the primary pattern of CNS response to WBRT and ipilimumab is stable disease and not regression of BM. Furthermore, while the combination of WBRT and ipilimumab may offer promising efficacy, prospective studies are needed to further assess efficacy and toxicity. PMID:25273687

  4. [Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases].

    PubMed

    Qu, Liyan; Geng, Rui; Song, Xia

    2016-08-20

    Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC) and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized. PMID:27561800

  5. New insights and emerging therapies for breast cancer brain metastases.

    PubMed

    Lim, Elgene; Lin, Nancy U

    2012-07-01

    Breast cancer brain metastases (BCBMs) are the second most frequent secondary central nervous system metastases following those associated with non-small-cell lung cancer. It is increasingly evident that BCBM arises as a function of the biology of the primary tumor and the metastatic niche, which combine to create a unique microenvironment in the brain impacting both metastatic colonization and therapeutic response. Clinical outcomes are improving for BCBM patients as a result of modern combinatorial therapies, challenging the traditionally nihilistic approach to this patient subgroup. This review will focus on the breast cancer subtypes with the highest incidence of BCBM-human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and triple-negative (estrogen receptor [ER]-negative, progesterone receptor [PR]-negative, and HER2-negative) breast cancer (TNBC)-and will characterize differences in the clinical behavior of brain metastases that arise from these different subtypes. We will also highlight some of the recent preclinical studies that may shed light on the biological mechanisms and mediators underlying brain metastases. Finally, we will review published and current prospective trials of systemic therapies specifically for BCBM, including novel pathway-specific therapies. PMID:22888567

  6. The Current and Future Treatment of Brain Metastases.

    PubMed

    Hardesty, Douglas A; Nakaji, Peter

    2016-01-01

    Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient's overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood-brain barrier transgression, cell-cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment. PMID:27252942

  7. The Current and Future Treatment of Brain Metastases

    PubMed Central

    Hardesty, Douglas A.; Nakaji, Peter

    2016-01-01

    Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient’s overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood–brain barrier transgression, cell–cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment. PMID:27252942

  8. [Supportive care, cognition and quality of life in brain metastases].

    PubMed

    Le Rhun, É; Taillibert, S; Blonski, M; Jouniaux Delbez, N; Delgadillo, D; Taillia, H; Auquier, P; Belin, C; Bonnetain, F; Varin, D; Tallet, A; Taillandier, L

    2015-02-01

    Brain metastases impact on the survival of the patients, but on their quality of life as well. The objective of the management of these patients is then double. Currently, due to medical advances, survivals tend to improve, especially for some tumor subtypes. During the course of the disease, different neurological signs and symptoms can be observed according to the location, the number and the volume of the metastase(s). Patients and caregivers are especially worried about the loss of autonomy and cognitive impairments. A permanent dialogue, during the course of the disease, is mandatory, in order to adapt the management to the objectives determined by the patients and the medical team. These objectives may vary according to the objective response rates of the disease to anticancer therapies, according to the impact of the disease and its management in daily living. Anticancer therapies and supportive care must be appreciated according to their impact on the survival, on the preservation of the functional independence and the quality of life of the patient, on their abilities to preserve the neurological status and delay the apparition of new neurological signs and symptoms, and their adverse events. Supportive care, cognition and quality of life should be regularly evaluated and adapted according to the objectives of the management of brain metastases patients. Different approaches are described in this paper. PMID:25640218

  9. [Acute lymphoblastic leukemia presenting with multiple hemorrhagic brain metastases (case report)].

    PubMed

    Halefoğlu, Ahmet M; Ertürk, Mehmet; Ozel, Alper; Calişkan, K Can

    2004-06-01

    Intracranial metastases represent 7-17% of all brain tumors. Renal cell carcinoma, thyroid cancer, choriocarcinoma, melanoma, retinoblastoma, lung cancer and breast cancer have a propensity for producing hemorrhagic brain metastases. Leukemias have also been rarely reported to cause hemorrhagic brain metastases. We describe an 18-year-old girl diagnosed as acute lymphoblastic leukemia presenting with multiple hemorrhagic brain metastases. MRI demonstrated high signal intensity lesions on both T1- and T2-weighted images which were characteristic for extracellular methemoglobin and consistent with hemorrhagic metastases. PMID:15236125

  10. Current and emerging treatments for brain metastases.

    PubMed

    Ba, Jenny Lin; Jandial, Rahul; Nesbit, Amanda; Badie, Behnam; Chen, Mike

    2015-04-01

    Brain metastasis in patients with cancer can be indicative of multisystem spread or lead to neurological demise if not locally controlled, and is associated with poor survival and high morbidity. Compared with metastasis to other areas of the body, brain metastasis possesses a unique biology that confers high resistance to systemic therapies. This phenomenon has been historically attributed to the inability of chemotherapeutic agents to pass through the blood-brain barrier. Recent studies challenge this premise, revealing other potentially targetable mechanism(s). Therapies that exploit recent advances in the understanding of brain metastasis are still in early stages of development. Encouragingly, and discovered by happenstance, some molecularly targeted drugs already appear to have efficacy against certain tumors and accompanying cerebral edema. In the meantime, conventional treatment modalities such as surgery and radiation have iteratively reached new levels of refinement. However, these achievements are somewhat muted by the emergence of magnetic resonance (MR)-guided laser interstitial thermal therapy, a minimally invasive neuroablative technique. On the horizon, MR-guided focused ultrasound surgery is similarly intriguing. Even in the absence of further advances, local control is frequently achieved with state-of-the-art therapies. Dramatic improvements will likely require sophisticated approaches that account for the particular effects of the microenvironment of the central nervous system on metastasis. PMID:25952487

  11. Radiation Therapy for the Management of Brain Metastases.

    PubMed

    Garrett, Matthew D; Wu, Cheng-Chia; Yanagihara, Ted K; Jani, Ashish; Wang, Tony J C

    2016-08-01

    Brain metastases are the most common malignant intracranial tumors and carry a poor prognosis. The management of brain metastases may include a variety of treatment modalities including surgical resection, radiation therapy, and/or systemic therapy. The traditional treatment for brain metastasis involved whole brain irradiation. However, improved systemic control of primary cancers has led to longer survival for some groups of patients and there is increasing need to consider the late effects of radiation to the entire brain. With advances in imaging and radiation treatment planning and delivery stereotactic radiosurgery has become more frequently utilized and may be delivered through Gamma Knife Stereotactic Radiosurgery or linear accelerator-based systems. Furthermore, experience in treating thousands of patients on clinical trials has led to diagnosis-specific prognostic assessment systems that help guide our approach to the management of this common clinical scenario. This review provides an overview of the literature supporting radiotherapy for brain metastasis and an update on current radiotherapeutic options that is tailored for the nonradiation oncologist. PMID:27213494

  12. Radiosurgery for Brain Metastases From Unknown Primary Cancers

    SciTech Connect

    Niranjan, Ajay; Kano, Hideyuki; Khan, Aftab; Kim, In-Young; Kondziolka, Douglas; Flickinger, John C.; Lunsford, L. Dade

    2010-08-01

    Purpose: We evaluated the role of Gamma Knife stereotactic radiosurgery in the multidisciplinary management of brain metastases from an undiagnosed primary cancer. Methods and Materials: Twenty-nine patients who had solitary or multiple brain metastases without a detectable primary site underwent stereotactic radiosurgery between January 1990 and March 2007 at the University of Pittsburgh. The median patient age was 61.7 years (range, 37.9-78.7 years). The median target volume was 1.0 cc (range, 0.02-23.6 cc), and the median margin radiosurgical dose was 16 Gy (range, 20-70 Gy). Results: After radiosurgery, the local tumor control rate was 88.5%. Twenty four patients died and 5 patients were living at the time of this analysis. The overall median survival was 12 months. Actuarial survival rates from stereotactic radiosurgery at 1 and 2 years were 57.2% and 36.8%, respectively. Factors associated with poor progression-free survival included large tumor volume (3 cc or more) and brainstem tumor location. Conclusions: Radiosurgery is an effective and safe minimally invasive option for patients with brain metastases from an unknown primary site.

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

    PubMed

    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. PMID:25043771

  14. Brain metastases management paradigm shift: A case report and review of the literature

    PubMed Central

    REFAAT, TAMER; SACHDEV, SEAN; DESAI, BRIJAL; BACCHUS, IAN; HATOUM, SALEH; LEE, PLATO; BLOCH, ORIN; CHANDLER, JAMES P.; KALAPURAKAL, JOHN; MARYMONT, MARYANNE HOFFMAN

    2016-01-01

    Brain metastases are the most common intracranial tumors in adults, accounting for over half of all lesions. Whole-brain radiation therapy (WBRT) has been a cornerstone in the management of brain metastases for decades. Recently, stereotactic radiosurgery (SRS) has been considered as a definitive or postoperative approach instead of WBRT, to minimize the risk of cognitive impairment that may be associated with WBRT. This is the case report of a 74-year-old female patient who was diagnosed with lung cancer in November, 2002, and histopathologically confirmed brain metastases in January, 2005. The patient received 5 treatments with Gamma Knife SRS for recurring brain metastases between 2005 and 2014. The patient remains highly functional, with stable intracranial disease at 10 years since first developing brain metastases, and with stable lung disease. Therefore, Gamma Knife SRS is a safe and effective treatment modality for patients with recurrent intracranial metastases, with durable local control and minimal cognitive impairment. PMID:27073647

  15. Innovative therapeutic strategies in the treatment of brain metastases.

    PubMed

    Caffo, Maria; Barresi, Valeria; Caruso, Gerardo; Cutugno, Mariano; La Fata, Giuseppe; Venza, Mario; Alafaci, Concetta; Tomasello, Francesco

    2013-01-01

    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. PMID:23340652

  16. Dose Escalation of Whole-Brain Radiotherapy for Brain Metastases From Melanoma

    SciTech Connect

    Rades, Dirk; Heisterkamp, Christine; Huttenlocher, Stefan; Bohlen, Guenther; Dunst, Juergen; Haatanen, Tiina; Schild, Steven E.

    2010-06-01

    Purpose: The majority of patients with brain metastases from melanoma receive whole-brain radiotherapy (WBRT). However, the results are poor. Hypofractionation regimens failed to improve the outcome of these patients. This study investigates a potential benefit from escalation of the WBRT dose beyond the 'standard' regimen 30 Gy in 10 fractions (10x3 Gy). Methods and Materials: Data from 51 melanoma patients receiving WBRT alone were retrospectively analyzed. A dosage of 10x3 Gy (n = 33) was compared with higher doses including 40 Gy/20 fractions (n = 11) and 45 Gy/15 fractions (n = 7) for survival (OS) and local (intracerebral) control (LC). Additional potential prognostic factors were evaluated: age, gender, performance status, number of metastases, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: At 6 months, OS rates were 27% after 10x3 Gy and 50% after higher doses (p = 0.009). The OS rates at 12 months were 4% and 20%. On multivariate analysis, higher WBRT doses (p = 0.010), fewer than four brain metastases (p = 0.012), no extracerebral metastases (p = 0.006), and RPA class 1 (p = 0.005) were associated with improved OS. The LC rates at 6 months were 23% after 10x3 Gy and 50% after higher doses (p = 0.021). The LC rates at 12 months were 0% and 13%. On multivariate analysis, higher WBRT doses (p = 0.020) and fewer than brain metastases (p = 0.002) were associated with better LC. Conclusions: Given the limitations of a retrospective study, the findings suggest that patients with brain metastases from melanoma receiving WBRT alone may benefit from dose escalation beyond 10x3 Gy. The hypothesis generated by this study must be confirmed in a randomized trial stratifying for significant prognostic factors.

  17. Health State Utilities for Patients with Brain Metastases

    PubMed Central

    Dosoretz, Arie P; Hayman, James A; Yu, James B

    2016-01-01

    Purpose: Estimating the cost-effectiveness of whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS), including Gamma Knife radiosurgery (GKRS), requires the quantitative measurement of patients’ health states after treatment. We sought to quantify individuals’ preferences for the relevant health states after WBRT or GKRS for brain metastases on a 0 to 1 scale, where 1 is perfect health and 0 is death. Methods: We prospectively measured utilities in patients with brain metastases evaluated at Yale for consideration of WBRT and/or GKRS, as well as oncology nurses who had cared for patients with brain metastases before and after WBRT or GKRS, using the Standard Gamble (SG) technique. Demographic information was also collected. Nonparametric tests were used to compare potential differences in utility values and for subgroups based on demographic characteristics. Results: There were 24 patients and 31 nurses who completed the study between December 2013 and May 2015. Median utilities ranged from 0.85 for the status-post (S/P) GKRS state to 0.25 (for neurologic dying). The median utility of being S/P WBRT was 0.70 compared to 0.85 S/P GKRS (p < 0.001). The cognitive decline from WBRT was associated with a notably low utility score of 0.30. There were no statistically significant differences between patients’ and nurses’ median utility scores. Conclusions: These SG utilities provide unique insights into brain metastases-related health states from the patient and provider perspective. As perceived by individuals with direct knowledge of the health states in question, WBRT has a significantly lower utility compared to GKRS. Cognitive decline following WBRT is associated with significant perceived reduction in quality of life. Differences in the relative importance of overall survival and quality of life with treatment existed between patients with different stages of disease. These utilities can be used to calculate quality-adjusted life

  18. Pre-treatment factors associated with detecting additional brain metastases at stereotactic radiosurgery.

    PubMed

    Wardak, Zabi; Augustyn, Alexander; Zhu, Hong; Mickey, Bruce E; Whitworth, Louis A; Madden, Christopher J; Barnett, Samuel L; Abdulrahman, Ramzi E; Nedzi, Lucien A; Timmerman, Robert D; Choe, Kevin S

    2016-06-01

    The number of brain metastases identified on diagnostic magnetic resonance imaging (MRI) is a key factor in consideration of stereotactic radiosurgery (SRS). However, additional lesions are often detected on high-resolution SRS-planning MRI. We investigated pre-treatment clinical characteristics that are associated with finding additional metastases at SRS. Patients treated with SRS for brain metastases between the years of 2009-2014 comprised the study cohort. All patients underwent frame-fixed, 1 mm thick MRI on the day of SRS. Patient, tumor, and treatment characteristics were analyzed for an association with increase in number of metastases identified on SRS-planning MRI. 289 consecutive SRS cases were analyzed. 725 metastases were identified on pre-treatment MRI and 1062 metastases were identified on SRS-planning MRI. An increase in the number of metastases occurred in 34 % of the cases. On univariate analysis, more than four metastases and the diameter of the largest lesion were significantly associated with an increase in number of metastases on SRS-planning MRI. When stratified by the diameter of the largest lesion into <2, 2-3, or ≥3 cm, additional metastases were identified in 37, 29, and 18 %, respectively. While this increase in the number of metastases is largely due to the difference in imaging technique, the number and size of the metastases were also associated with finding additional lesions. These clinical factors may be considered when determining treatment options for brain metastases. PMID:26966096

  19. Cabazitaxel in castration resistant prostate cancer with brain metastases: 3 case reports.

    PubMed

    De Placido, Sabino; Rescigno, Pasquale; Federico, Piera; Buonerba, Carlo; Bosso, Davide; Puglia, Livio; Izzo, Michela; Policastro, Tania; Di Lorenzo, Giuseppe

    2014-06-16

    Prostate cancer is the most common non-cutaneous malignancy for men. The skeleton is the most common metastatic site but, following an improvement in survival, metastases in uncommon sites are being found more frequently in clinical practice, especially brain metastases. Despite the new drugs now available for metastatic castration resistant prostate cancer, no clinical evidence exists about their effectiveness on brain metastases. We describe the clinical history of 3 patients treated with cabazitaxel plus whole brain radiotherapy. These case reports demonstrate that cabazitaxel is highly active and well tolerated in brain metastases. PMID:24945013

  20. Cabazitaxel in castration resistant prostate cancer with brain metastases: 3 case reports

    PubMed Central

    Placido, Sabino De; Rescigno, Pasquale; Federico, Piera; Buonerba, Carlo; Bosso, Davide; Puglia, Livio; Izzo, Michela; Policastro, Tania; Lorenzo, Giuseppe Di

    2014-01-01

    Prostate cancer is the most common non-cutaneous malignancy for men. The skeleton is the most common metastatic site but, following an improvement in survival, metastases in uncommon sites are being found more frequently in clinical practice, especially brain metastases. Despite the new drugs now available for metastatic castration resistant prostate cancer, no clinical evidence exists about their effectiveness on brain metastases. We describe the clinical history of 3 patients treated with cabazitaxel plus whole brain radiotherapy. These case reports demonstrate that cabazitaxel is highly active and well tolerated in brain metastases. PMID:24945013

  1. 18F-NaF PET/CT Imaging of Brain Metastases.

    PubMed

    Salgarello, Matteo; Lunardi, Gianluigi; Inno, Alessandro; Pasetto, Stefano; Severi, Fabrizia; Gorgoni, Giancarlo; Gori, Stefania

    2016-07-01

    F-NaF is a radiopharmaceutical widely used in PET imaging to detect bone metastases. Several cases of F-NaF uptake from brain metastases have been described, but a specific protocol for the evaluation of brain metastases with F-NaF has not been developed yet. Here we report images of F-NaF PET/CT, standard CT, and MRI of a brain metastasis in a patient with non-small lung cancer. Through a dynamic acquisition procedure, we have identified the first minutes after injection as the preferable time point of imaging acquisition for the study of brain metastases with F-NaF. PMID:27163462

  2. Tumor bed radiosurgery: an emerging treatment for brain metastases.

    PubMed

    Amsbaugh, Mark J; Boling, Warren; Woo, Shiao

    2015-06-01

    While typically used for treating small intact brain metastases, an increasing body of literature examining tumor bed directed stereotactic radiosurgery (SRS) is emerging. There are now over 1000 published cases treated with this approach, and the first prospective trial was recently published. The ideal sequencing of tumor bed SRS is unclear. Current approaches include, a neoadjuvant treatment before resection, alone as an adjuvant after resection, and following surgery combined with whole brain radiotherapy either as an adjuvant or salvage treatment. Based on available evidence, adjuvant stereotactic radiosurgery improves local control following surgery, reduces the number of patients who require whole brain radiotherapy, and is well tolerated. While results from published series vary, heterogeneity in both patient populations and methods of reporting results make comparisons difficult. Additional prospective data, including randomized trials are needed to confirm equivalent outcomes to the current standard of care. We review the current literature, identify areas of ongoing contention, and highlight ongoing studies. PMID:25911296

  3. Current Perspectives in the Management of Brain Metastases.

    PubMed

    Saria, Marlon G; Piccioni, David; Carter, Joshua; Orosco, Heather; Turpin, Tiffany; Kesari, Santosh

    2015-08-01

    Brain metastases (BMs) are diagnosed in 10%-40% of all patients with cancer, and the incidence continues to increase along with the number of long-term survivors. When BMs occur, they are often associated with a myriad of symptoms, including neurologic dysfunction and functional decline; both are difficult to manage and can be distressing for patients and their caregivers. Although clinically significant findings have not kept up with the rapid pace of scientific breakthroughs in understanding the mechanisms of BMs, novel approaches that affect the prognosis of patients with BMs have been introduced in clinical practice. At a Glance • Screening for brain metastases (BMs) is not routinely performed in patients with no neurologic symptoms. However, screening is indicated in lung cancer and possibly in the context of high-risk cancers. • Individual differences in patients warrant a personalized approach in the management of BMs. • Whole brain radiation therapy and steroids are considered to be the cornerstones of treatment for BMs. PMID:26207714

  4. Stereotactic radiosurgery in elderly patients with brain metastases.

    PubMed

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

    2013-02-01

    Stereotactic radiosurgery (SRS) has been increasingly employed as an alternative to whole brain radiation therapy in patients with brain metastases, with the aim to reduce its potential toxicity. We have evaluated clinical outcomes of SRS as initial treatment for brain metastases in patients 70 years and older. Between November 2007 and October 2011, 102 patients of 70 years and older with 1-4 metastases were treated with SRS. The primary end point of the study was overall survival. Secondary end points were local control and distant failure rates, cause of death, performance measurements, and toxicity of treatment. At a median follow-up of 11.0 months (range 1-48 months), median survival and median time to distant failure were 13.2 and 10 months, respectively. The 1- and 2-year survival rates were 63 and 28 %, and respective distant failure rates were 54 and 78 %. Forty-five patients succumbed to their extracranial disease and 14 patients died of progressive intracranial disease. Nine patients recurred locally after SRS. The 1- and 2-year local control rates were 90 and 84 %, respectively. Evaluation of neurocognitive function using the Mini-Mental State Examination (MMSE) showed no significant neurocognitive decline after SRS. MMSE score improved in 15 % of patients, worsened in 12 % of patients, and remained stable in the others. Severe neurological complications were reported in 7 (7 %) patients, requiring surgery or medical treatment. Initial treatment with SRS with close monitoring may represent a relatively safe treatment strategy associated with survival benefit, with outcomes similar to those reported in historical series of SRS for younger patients. PMID:23187817

  5. Shorter-Course Whole-Brain Radiotherapy for Brain Metastases in Elderly Patients

    SciTech Connect

    Rades, Dirk; Evers, Jasmin N.; Veninga, Theo; Stalpers, Lukas J.A.; Lohynska, Radka; Schild, Steven E.

    2011-11-15

    Purpose: Many patients with brain metastases receive whole-brain radiotherapy (WBRT) alone. Using 10 Multiplication-Sign 3 Gy in 2 weeks is the standard regimen in most centers. Regarding the extraordinarily poor survival prognosis of elderly patients with multiple brain metastases, a shorter WBRT regimen would be preferable. This study compared 10 Multiplication-Sign 3 Gy with 5 Multiplication-Sign 4 Gy in elderly patients ({>=}65 years). Methods and Materials: Data from 455 elderly patients who received WBRT alone for brain metastases were retrospectively analyzed. Survival and local (= intracerebral) control of 293 patients receiving 10 Multiplication-Sign 3 Gy were compared with 162 patients receiving 5 Multiplication-Sign 4 Gy. Eight additional potential prognostic factors were investigated including age, gender, Karnofsky performance score (KPS), primary tumor, number of brain metastases, interval from tumor diagnosis to WBRT, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: The 6-month overall survival rates were 29% after 5 Multiplication-Sign 4 Gy and 21% after 10 Multiplication-Sign 3 Gy (p = 0.020). The 6-month local control rates were 12% and 10%, respectively (p = 0.32). On multivariate analysis, improved overall survival was associated with KPS {>=} 70 (p < 0.001), only one to three brain metastases (p = 0.029), no extracerebral metastasis (p = 0.012), and lower RPA class (p < 0.001). Improved local control was associated with KPS {>=} 70 (p < 0.001), breast cancer (p = 0.029), and lower RPA class (p < 0.001). Conclusions: Shorter-course WBRT with 5 Multiplication-Sign 4 Gy was not inferior to 10 Multiplication-Sign 3 Gy with respect to overall survival or local control in elderly patients. 5 Multiplication-Sign 4 Gy appears preferable for the majority of these patients.

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

    PubMed

    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. PMID:25649388

  7. Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets

    PubMed Central

    Santagata, Sandro; Cahill, Daniel P.; Taylor-Weiner, Amaro; Jones, Robert T.; Van Allen, Eliezer M.; Lawrence, Michael S.; Horowitz, Peleg M.; Cibulskis, Kristian; Ligon, Keith L.; Tabernero, Josep; Seoane, Joan; Martinez-Saez, Elena; Curry, William T.; Dunn, Ian F.; Paek, Sun Ha; Park, Sung-Hye; McKenna, Aaron; Chevalier, Aaron; Rosenberg, Mara; Barker, Frederick G.; Gill, Corey M.; Van Hummelen, Paul; Thorner, Aaron R.; Johnson, Bruce E.; Hoang, Mai P.; Choueiri, Toni K.; Signoretti, Sabina; Sougnez, Carrie; Rabin, Michael S.; Lin, Nancy U.; Winer, Eric P.; Stemmer-Rachamimov, Anat; Meyerson, Matthew; Garraway, Levi; Gabriel, Stacey; Lander, Eric S.; Beroukhim, Rameen; Batchelor, Tracy T.; Baselga, Jose; Louis, David N.

    2016-01-01

    Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases. PMID:26410082

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

    PubMed Central

    Tallet, Agnes V.; Azria, David; Le Rhun, Emilie; Barlesi, Fabrice; Carpentier, Antoine F.; Gonçalves, Antony; Taillibert, Sophie; Dhermain, Frédéric; Spano, Jean-Philippe; Metellus, Philippe

    2014-01-01

    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. PMID:24815073

  9. Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression. A report from the RANO group.

    PubMed

    Lin, Nancy U; Lee, Eudocia Q; Aoyama, Hidefumi; Barani, Igor J; Baumert, Brigitta G; Brown, Paul D; Camidge, D Ross; Chang, Susan M; Dancey, Janet; Gaspar, Laurie E; Harris, Gordon J; Hodi, F Stephen; Kalkanis, Steven N; Lamborn, Kathleen R; 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; Wefel, Jeffrey S; Wen, Patrick Y

    2013-09-01

    Therapeutic outcomes for patients with brain metastases need to improve. A critical review of trials specifically addressing brain metastases shows key issues that could prevent acceptance of results by regulatory agencies, including enrolment of heterogeneous groups of patients and varying definitions of clinical endpoints. Considerations specific to disease, modality, and treatment are not consistently addressed. Additionally, the schedule of CNS imaging and consequences of detection of new or progressive brain metastases in trials mainly exploring the extra-CNS activity of systemic drugs are highly variable. The Response Assessment in Neuro-Oncology (RANO) working group is an independent, international, collaborative effort to improve the design of trials in patients with brain tumours. In this two-part series, we review the state of clinical trials of brain metastases and suggest a consensus recommendation for the development of criteria for future clinical trials. PMID:23993384

  10. Early-onset brain metastases in a breast cancer patient after pathological complete response to neoadjuvant chemotherapy.

    PubMed

    Shimada, Kazuhiro; Ishikawa, Takashi; Yoneyama, Shuko; Kita, Kumiko; Narui, Kazutaka; Sugae, Sadayoshi; Shimizu, Daisuke; Tanabe, Mikiko; Sasaki, Takeshi; Chishima, Takashi; Ichikawa, Yasushi; Endo, Itaru

    2013-11-01

    Breast cancer patients who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) usually have a favourable prognosis. We report on a patient with early metastases to the brain after achieving pCR. The primary tumour was 7.0 cm in diameter with axillary lymph node metastases, hormone receptor-negative, human epidermal growth factor receptor-2-positive (3+), and histological grade 2 with 60% of cells positive for Ki-67. The patient underwent NAC followed by surgery, and achieved pCR. Five months after surgery, during adjuvant treatment with trastuzumab, she developed headache and dizziness. Brain imaging revealed multiple metastatic brain tumours. She received whole-brain radiotherapy followed by lapatinib and capecitabine therapy. At 7 months after surgery, she remains alive with a persistent mild headache. Physicians should be aware of the possibility of early brain metastases, and consider new treatment strategies to prevent brain metastases in high-risk patients who achieve pCR. PMID:24222158

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

    SciTech Connect

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

    2008-12-01

    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.

  12. ROS1 rearranged non-small cell lung cancer brain metastases respond to low dose radiotherapy.

    PubMed

    Lukas, Rimas V; Hasan, Yasmin; Nicholas, Martin K; Salgia, Ravi

    2015-12-01

    We present a young woman with ROS1 gene rearranged non-small cell lung cancer (NSCLC) with brain metastases. ROS is a proto-oncogene tyrosine protein kinase. The patient received a partial course of whole brain radiation therapy and experienced a sustained partial response in the brain. We hypothesize that ROS1 rearranged NSCLC brain metastases may be particularly sensitive to radiation therapy. PMID:26159887

  13. [Advances in diagnosis and treatment of brain metastases from the primary lung cancer].

    PubMed

    Liu, Yi; Chen, Jun

    2013-07-01

    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. PMID:23866671

  14. Prevention of Bone Metastases in Breast Cancer Patients. Therapeutic Perspectives

    PubMed Central

    Beuzeboc, Philippe; Scholl, Suzy

    2014-01-01

    One in four breast cancer patients is at risk of developing bone metastases in her life time. The early prevention of bone metastases is a crucial challenge. It has been suggested that the use of zoledronic acid (ZOL) in the adjuvant setting may reduce the persistence of disseminated tumor cells and thereby might improve outcome, specifically in a population of patients with a low estrogen microenvironment. More recently, the results of a large meta-analysis from 41 randomized trials comparing a bisphosphonate (BP) to placebo or to an open control have been presented at the 2013 San Antonio Breast Cancer Meeting. Data on 17,016 patients confirm that adjuvant BPs, irrespective of the type of treatment or the treatment schedule and formulation (oral or intra-venously (IV)), significantly reduced bone recurrences and improved breast cancer survival in postmenopausal women. No advantage was seen in premenopausal women. BPs are soon likely to become integrated into standard practice. Published data on the mechanisms involved in tumor cell seeding from the primary site, in homing to bone tissues and in the reactivation of dormant tumor cells will be reviewed; these might offer new ideas for innovative combination strategies. PMID:26237389

  15. Treatment of Five or More Brain Metastases With Stereotactic Radiosurgery

    SciTech Connect

    Hunter, Grant K.; Suh, John H.; Reuther, Alwyn M.; Vogelbaum, Michael A.; Barnett, Gene H.; Angelov, Lilyana; Weil, Robert J.; Neyman, Gennady; Chao, Samuel T.

    2012-08-01

    Purpose: To examine the outcomes of patients with five or more brain metastases treated in a single session with stereotactic radiosurgery (SRS). Methods and Materials: Sixty-four patients with brain metastases treated with SRS to five or more lesions in a single session were reviewed. Primary disease type, number of lesions, Karnofsky performance score (KPS) at SRS, and status of primary and systemic disease at SRS were included. Patients were treated using dosing as defined by Radiation Therapy Oncology Group Protocol 90-05, with adjustments for critical structures. We defined prior whole-brain radiotherapy (WBRT) as WBRT completed >1 month before SRS and concurrent WBRT as WBRT completed within 1 month before or after SRS. Kaplan-Meier estimates and Cox proportional hazard regression were used to determine which patient and treatment factors predicted overall survival (OS). Results: The median OS after SRS was 7.5 months. The median KPS was 80 (range, 60-100). A KPS of {>=}80 significantly influenced OS (median OS, 4.8 months for KPS {<=}70 vs. 8.8 months for KPS {>=}80, p = 0.0097). The number of lesions treated did not significantly influence OS (median OS, 6.6 months for eight or fewer lesions vs. 9.9 months for more than eight, p = nonsignificant). Primary site histology did not significantly influence median OS. On multivariate Cox modeling, KPS and prior WBRT significantly predicted for OS. Whole-brain radiotherapy before SRS compared with concurrent WBRT significantly influenced survival, with a risk ratio of 0.423 (95% confidence interval 0.191-0.936, p = 0.0338). No significant differences were observed when no WBRT was compared with concurrent WBRT or when the no WBRT group was compared with prior WBRT. A KPS of {<=}70 predicted for poorer outcomes, with a risk ratio of 2.164 (95% confidence interval 1.157-4.049, p = 0.0157). Conclusions: Stereotactic radiosurgery to five or more brain lesions is an effective treatment option for patients with

  16. Single-Dose Versus Fractionated Stereotactic Radiotherapy for Brain Metastases

    SciTech Connect

    Kim, Yeon-Joo; Cho, Kwan Ho; Kim, Joo-Young; Lim, Young Kyung; Min, Hye Sook; Lee, Sang Hyun; Kim, Ho Jin; Gwak, Ho Shin; Yoo, Heon; Lee, Seung Hoon

    2011-10-01

    Purpose: To evaluate the efficacy of stereotactic radiotherapy in patients with brain metastases by comparing two different treatment regimens, single-dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Between November 2003 and December 2008, 98 patients with brain metastases were included. Fifty-eight patients were treated with SRS, and forty were treated with FSRT. Fractionated stereotactic radiotherapy was used for large lesions or lesions located near critical structures. The median doses were 20 Gy for the SRS group and 36 Gy in 6 fractions for the FSRT group. Results: With a median follow-up period of 7 months, the median survival was 7 months for all patients, with a median of 6 months for the SRS group and 8 months for the FSRT group (p = 0.89). Local progression-free survival (LPFS) rates at 6 months and 1 year were 81% and 71%, respectively, for the SRS group and 97% and 69%, respectively, for the FSRT group (p = 0.31). Despite the fact that FSRT was used for large lesions and lesions in adverse locations, LPFS was not inferior to SRS. Toxicity was more frequently observed in the SRS group than in the FSRT group (17% vs. 5%, p = 0.05). Conclusions: Because patients treated with FSRT exhibited similar survival times and LPFS rates with a lower risk of toxicity in comparison to those treated with SRS, despite the fact that FSRT was used for large lesions and lesions in adverse locations, we find that FSRT can particularly be beneficial for patients with large lesions or lesions located near critical structures. Further investigation is warranted to determine the optimal dose/fractionation.

  17. The treatment of recurrent brain metastases with stereotactic radiosurgery.

    PubMed

    Loeffler, J S; Kooy, H M; Wen, P Y; Fine, H A; Cheng, C W; Mannarino, E G; Tsai, J S; Alexander, E

    1990-04-01

    Between May 1986 and August 1989, we treated 18 patients with 21 recurrent or persistent brain metastases with stereotactic radiosurgery using a modified linear accelerator. To be eligible for radiosurgery, patients had to have a performance status of greater than or equal to 70% and have no evidence of (or stable) systemic disease. All but one patient had received prior radiotherapy, and were treated with stereotactic radiosurgery at the time of recurrence. Polar lesions were treated only if the patient had undergone and failed previous complete surgical resection (10 patients). Single doses of radiation (900 to 2,500 cGy) were delivered to limited volumes (less than 27 cm3) using a modified 6MV linear accelerator. The most common histology of the metastatic lesion was carcinoma of the lung (seven patients), followed by carcinoma of the breast (four patients), and melanoma (four patients). With median follow-up of 9 months (range, 1 to 39), all tumors have been controlled in the radiosurgery field. Two patients failed in the immediate margin of the treated volume and were subsequently treated with surgery and implantation of 125I to control the disease. Radiographic response was dramatic and rapid in the patients with adenocarcinoma, while slight reduction and stabilization occurred in those patients with melanoma, renal cell carcinoma, and sarcoma. The majority of patients improved neurologically following treatment, and were able to be withdrawn from corticosteroid therapy. Complications were limited and transient in nature and no cases of symptomatic radiation necrosis occurred in any patient despite previous exposure to radiotherapy. Stereotactic radiosurgery is an effective and relatively safe treatment for recurrent solitary metastases and is an appealing technique for the initial management of deep-seated lesions as a boost to whole brain radiotherapy. PMID:2179476

  18. [Systemic treatment of brain metastases from breast cancer: cytotoxic chemotherapy and targeted therapies].

    PubMed

    Bachelot, Thomas; Le Rhun, Emilie; Labidi-Gally, Intidar; Heudel, Pierre; Gilabert, Marine; Bonneterre, Jacques; Pierga, Jean-Yves; Gonçalves, Anthony

    2013-01-01

    Prevalence of brain metastases is increasing in breast cancer. Brain metastases represent a poor-prognosis disease for which local treatments continue to play a major role. In spite of the presence of a physiological blood-brain barrier limiting their activity, some systemic treatments may display a significant antitumor activity at the central nervous system level. In HER2-positive metastatic breast cancer with brain metastases not previously treated with whole brain radiotherapy, capecitabine and lapatinib combination obtains a volumetric reponse in two thirds of patients (LANDSCAPE study). If confirmed, these results could modify in selected patients the layout of therapeutic strategies. Promoting novel targeted approaches and innovative therapeutic combinations is a critical need to improve survival of breast cancer patients with brain metastases. PMID:23305997

  19. Brain Metastases in Gastrointestinal Cancers: Is there a Role for Surgery?

    PubMed Central

    Lemke, Johannes; Scheele, Jan; Kapapa, Thomas; von Karstedt, Silvia; Wirtz, Christian Rainer; Henne-Bruns, Doris; Kornmann, Marko

    2014-01-01

    About 10% of all cancer patients will develop brain metastases during advanced disease progression. Interestingly, the vast majority of brain metastases occur in only three types of cancer: Melanoma, lung and breast cancer. In this review, we focus on summarizing the prognosis and impact of surgical resection of brain metastases originating from gastrointestinal cancers such as esophageal, gastric, pancreatic and colorectal cancer. The incidence of brain metastases is <1% in pancreatic and gastric cancer and <4% in esophageal and colorectal cancer. Overall, prognosis of these patients is very poor with a median survival in the range of only months. Interestingly, a substantial number of patients who had received surgical resection of brain metastases showed prolonged survival. However, it should be taken into account that all these studies were not randomized and it is likely that patients selected for surgical treatment presented with other important prognostic factors such as solitary brain metastases and exclusion of extra-cranial disease. Nevertheless, other reports have demonstrated long-term survival of patients upon resection of brain metastases originating from gastrointestinal cancers. Thus, it appears to be justified to consider aggressive surgical approaches for these patients. PMID:25247579

  20. The Brain Metastases Symptom Checklist as a novel tool for symptom measurement in patients with brain metastases undergoing whole-brain radiotherapy

    PubMed Central

    Rodin, D.; Banihashemi, B.; Wang, L.; Lau, A.; Harris, S.; Levin, W.; Dinniwell, R.; Millar, B.A.; Chung, C.; Laperriere, N.; Bezjak, A.; Wong, R.K.S.

    2016-01-01

    Purpose We evaluated the feasibility, reliability, and validity of the Brain Metastases Symptom Checklist (bmsc), a novel self-report measure of common symptoms experienced by patients with brain metastases. Methods Patients with first-presentation symptomatic brain metastases (n = 137) referred for whole-brain radiotherapy (wbrt) completed the bmsc at time points before and after treatment. Their caregivers (n = 48) provided proxy ratings twice on the day of consultation to assess reliability, and at week 4 after wbrt to assess responsiveness to change. Correlations with 4 other validated assessment tools were evaluated. Results The symptoms reported on the bmsc were largely mild to moderate, with tiredness (71%) and difficulties with balance (61%) reported most commonly at baseline. Test–retest reliability for individual symptoms had a median intraclass correlation of 0.59 (range: 0.23–0.85). Caregiver proxy and patient responses had a median intraclass correlation of 0.52. Correlation of absolute scores on the bmsc and other symptom assessment tools was low, but consistency in the direction of symptom change was observed. At week 4, change in symptoms was variable, with improvements in weight gain and sleep of 42% and 41% respectively, and worsening of tiredness and drowsiness of 62% and 59% respectively. Conclusions The bmsc captures a wide range of symptoms experienced by patients with brain metastases, and it is sensitive to change. It demonstrated adequate test–retest reliability and face validity in terms of its responsiveness to change. Future research is needed to determine whether modifications to the bmsc itself or correlation with more symptom-specific measures will enhance validity. PMID:27330360

  1. Concurrent capecitabine and whole-brain radiotherapy for treatment of brain metastases in breast cancer patients.

    PubMed

    Chargari, Cyrus; Kirova, Youlia M; Diéras, Véronique; Castro Pena, Pablo; Pena, Pablo Castro; Campana, Francois; Cottu, Paul H; Pierga, JeanYves; Fourquet, Alain

    2009-07-01

    Preclinical data have demonstrated that ionizing radiation acts synergistically with capecitabine. This report retrospectively assessed the use of capecitabine concurrently with whole-brain radiotherapy (WBRT) in patients with brain metastases from breast cancer. From January 2003 to March 2005, five breast cancer patients with brain metastases were referred for WBRT with concurrent capecitabine. Median age was 44 years (range: 38-53). The median dose of capecitabine was 1,000 mg/m(2) twice daily for 14 days (day1-14). Treatment cycles were repeated every 21 days, concurrently with WBRT (30 Gy, 3 Gy per fraction, 5 days per week). Median survival after starting WBRT plus capecitabine was 6.5 months (range 1-34 months). One patient achieved a complete response. Two patients achieved partial response, including one with local control lasting until most recent follow-up. One patient had stable disease. The remaining patient was not assessable for response because of early death. Most commonly reported adverse events were nausea (n = 2) and headache (n = 2), always grade 1. Other toxicities were grade 3 hand/foot syndrome (n = 1), moderate anemia requiring transfusion and dose reduction of capecitabine (n = 1), and grade 1 mucositis (n = 1). Although promising, these preliminary data warrant further assessment of capecitabine-based chemoradiation in brain metastases from breast cancer and need to be further validated in the setting of a clinical trial. PMID:19169856

  2. BM-35CLINICAL FACTORS IMPACTING SURVIVAL IN BRAIN METASTASES

    PubMed Central

    Veilleux, Olivier; Cottin, Sylvine; Michaud, Karine

    2014-01-01

    BACKGROUND: Metastatic brain tumors are a common complication of systemic cancers. Good performance status, absence of extracranial metastases, age < 65 years and control of the primary tumor are the strongest predictors of survival. Controversy exists regarding best adjuvant treatment for patients. Therefore, careful evaluation of patient features and tumor characteristics must be considered when determining treatment modality. OBJECTIVES: The aim of the study was to assess the treatment management and clinical features of metastatic brain neoplasms following a neurosurgical procedure and evaluate factors conditioning survival. METHODS: Between January 1st 2009 and January 1st 2013, medical files of patients who underwent a surgical procedure for metastatic brain tumors at Hôpital de l'Enfant-Jésus in Québec City were reviewed. Data on patient features, primary and metastatic neoplasm characteristics, procedure and survival were recorded. Wilcoxon rank sum test, Kruskal-Wallis test and Cox proportional-hazards regression for survival data were used to assess the impact of treatments and patient characteristics on survival. Efficacy of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) and combined treatment in terms of patient survival were also evaluated. RESULTS: One hundred and twenty six patient files were reviewed and 109 were included for analysis. The mean survival time for patients was 537.9 days. Age below 65 years (p = 0.08) was a protective factor. WBRT combined with SRS (p < 0.0001), the use of WBRT alone (p = 0.002) or SRS alone (p = 0.004) all significantly improved survival. SRS, when compared to WBRT alone or to combined WBRT and SRS treatment, did not show significant difference in survival. CONCLUSION: Survival in our population is influenced by age and the use of adjuvant treatment. The choice of treatment modality after surgery remains somewhat controversial and our results support the need for further studies to compare

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

    PubMed

    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

    2015-06-01

    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 in the response and progression criteria used across clinical trials. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group is an international, multidisciplinary effort to develop standard response and progression criteria for use in clinical trials of treatment for brain metastases. Previous efforts have focused on aspects of trial design, such as patient population, variations in existing response and progression criteria, and challenges when incorporating neurological, neuro-cognitive, and quality-of-life endpoints into trials of patients with brain metastases. Here, we present our recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials. The proposed criteria will hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity in the assessment of CNS metastases across trials. PMID:26065612

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

    SciTech Connect

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

    1989-06-01

    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.

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

    SciTech Connect

    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.

  6. Prognostic Indexes for Brain Metastases: Which Is the Most Powerful?

    SciTech Connect

    Arruda Viani, Gustavo; Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose

    2012-07-01

    Purpose: The purpose of the present study was to compare the prognostic indexes (PIs) of patients with brain metastases (BMs) treated with whole brain radiotherapy (WBRT) using an artificial neural network. This analysis is important, because it evaluates the prognostic power of each PI to guide clinical decision-making and outcomes research. Methods and Materials: A retrospective prognostic study was conducted of 412 patients with BMs who underwent WBRT between April 1998 and March 2010. The eligibility criteria for patients included having undergone WBRT or WBRT plus neurosurgery. The data were analyzed using the artificial neural network. The input neural data consisted of all prognostic factors included in the 5 PIs (recursive partitioning analysis, graded prognostic assessment [GPA], basic score for BMs, Rotterdam score, and Germany score). The data set was randomly divided into 300 training and 112 testing examples for survival prediction. All 5 PIs were compared using our database of 412 patients with BMs. The sensibility of the 5 indexes to predict survival according to their input variables was determined statistically using receiver operating characteristic curves. The importance of each variable from each PI was subsequently evaluated. Results: The overall 1-, 2-, and 3-year survival rate was 22%, 10.2%, and 5.1%, respectively. All classes of PIs were significantly associated with survival (recursive partitioning analysis, P < .0001; GPA, P < .0001; basic score for BMs, P = .002; Rotterdam score, P = .001; and Germany score, P < .0001). Comparing the areas under the curves, the GPA was statistically most sensitive in predicting survival (GPA, 86%; recursive partitioning analysis, 81%; basic score for BMs, 79%; Rotterdam, 73%; and Germany score, 77%; P < .001). Among the variables included in each PI, the performance status and presence of extracranial metastases were the most important factors. Conclusion: A variety of prognostic models describe the

  7. Efficacy and Safety of Bevacizumab in Active Brain Metastases from Non-Small Cell Lung Cancer

    PubMed Central

    De Braganca, Kevin C.; Janjigian, Yelena Y.; Azzoli, Christopher G.; Kris, Mark G.; Pietanza, Maria C.; Nolan, Craig P.; Omuro, Antonio M.; Holodny, Andrei I.; Lassman, Andrew B.

    2011-01-01

    Background Bevacizumab is effective for the treatment of non-small cell lung cancer (NSCLC). Ongoing trials are exploring the safety of bevacizumab in patients with inactive, previously treated brain metastases. However, bevacizumab safety and efficacy in the treatment of active brain metastases is unknown. Bevacizumab received accelerated FDA approval for progressive glioblastoma, a primary brain tumor, because of high response rates and low incidence of intracranial hemorrhage. Methods We retrospectively identified patients treated with bevacizumab for active (treatment naïve or progressive) central nervous system (CNS) metastases from NSCLC. MRI scans performed at least 6 weeks after initiating bevacizumab were assessed for response. Results There were six patients, four women and two men with a median age of 60 years (range 59–77) at initiation of bevacizumab. Five patients had progressive CNS metastases despite prior treatment including surgery, radiotherapy, and/or chemotherapy; one patient had treatment-naïve brain metastases. Two patients had leptomeningeal metastases, isolated or coexistent with parenchymal brain metastases in one patient each. Bevacizumab was administered alone to one patient and in combination with various cytotoxic chemotherapies in the others. Toxicity included an asymptomatic (Grade 1) intra-tumoral hemorrhage which occurred in one of three patients receiving concurrent anticoagulation with bevacizumab. There was no recurrent CNS bleeding in two patients with a prior history of such hemorrhage. Best response (RECIST) was partial in two, stable disease in three, and progression in one. Median progression-free survival (PFS) was 4.7 months and median overall survival (OS) was 14.1 months following initiation of bevacizumab. Clinical benefit was also observed in the form of improved symptoms and reduced corticosteroid requirements. Conclusions Bevacizumab should be used with caution in patients with active CNS metastases pending

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

    SciTech Connect

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

    2013-04-01

    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.

  9. Complete response of brain metastases from breast cancer overexpressing Her-2/neu to radiation and concurrent Lapatinib and Capecitabine.

    PubMed

    Abboud, Mirna; Saghir, Nagi S El; Salame, Joseph; Geara, Fady B

    2010-01-01

    Breast cancers that overexpress the human epidermal growth factor receptor 2 (HER-2) have a predilection to metastasize to the brain. Therapeutic options for brain metastases with systemic therapy remain a challenge in those patients since targeted and chemotherapeutic agents have limited penetration through the blood-brain barrier. Here we report the case of a patient with brain metastases from breast cancer overexpressing HER-2 who achieved a complete radiologic response after treatment by radiation and concurrent Lapatinib and Capecitabine. PMID:21070441

  10. A pathology-based substrate for target definition in radiosurgery of brain metastases

    SciTech Connect

    Baumert, Brigitta G. . E-mail: brigitta.baumert@maastro.nl; Rutten, Isabelle; Dehing-Oberije, Cary M.Sc.; Twijnstra, Albert; Dirx, Miranda J.M.; Debougnoux-Huppertz, Ria M.T.L.; Lambin, Philippe; Kubat, Bela

    2006-09-01

    Purpose: To investigate the need of a margin other than for accuracy reasons in stereotactic radiosurgery (SRS) of brain metastases by means of histopathology. Methods and Materials: Evaluation of 45 patients from two pathology departments having had brain metastases and an autopsy of the brain. Growth patterns were reviewed with a focus on infiltration beyond the metastases boundary and made visible with immunohistochemical staining: the metastasis itself with tumor-specific markers, surrounding normal brain tissue with a glial marker, and a possible capsule with a soft tissue marker. Measurements were corrected by a tissue-shrinkage correction factor taken from literature. Outcomes parameters for infiltration were mean and maximum depths of infiltration and number of measured infiltration sites. Results: In 48 of 76 metastases, an infiltration was present. The largest group of metastases was lung cancer. Small-cell lung cancer (SCLC) and melanoma showed a maximum depth of infiltration of {>=}1 mm, and other histologies <1 mm. For non-small-cell lung cancer (NSCLC), melanoma, and sarcoma, the highest number of infiltrative sites were observed (median, 2; range, 1-8). SCLC showed significantly larger infiltrative growth, compared with other diagnostic groups. In NSCLC, the highest percentage of infiltration was present (70%). Conclusions: Infiltrative growth beyond the border of the brain metastasis was demonstrated in 63% of the cases evaluated. Infiltrative growth, therefore, has an impact in defining the clinical target volume for SRS of brain metastases, and a margin of {approx}1 mm should be added to the visible lesion.

  11. Treatment of high numbers of brain metastases with Gamma Knife radiosurgery: a review.

    PubMed

    Hatiboglu, Mustafa Aziz; Tuzgen, Saffet; Akdur, Kerime; Chang, Eric L

    2016-04-01

    Effectiveness of stereotactic radiosurgery (SRS) has been shown in patients with one to four brain metastases. Work has been done to evaluate the role of SRS alone treatment without whole-brain radiation therapy in patients with more than four metastases. A recent multiinstitutional JLGK 0901 prospective study revealed the class-2 evidence that SRS without whole-brain radiation therapy is an effective treatment for patients up to 10 metastatic lesions. Several retrospective studies exist to show the efficacy and safety of SRS for patients with even more than 10 lesions. However, patient selection is very critical for SRS alone treatment. The PubMed database was searched using combinations of search terms and synonyms for multiple brain metastases, Gamma Knife and SRS published between January 1, 2005 and January 1, 2015 in order to address the effectiveness of Gamma Knife for patients with multiple brain metastases. Good performance status, controlled primary disease, total treated tumor volume of 15 cm(3) or less have been found to be significant predictors for survival among patients with two or more brain lesions. The data suggest that SRS can be used and whole brain radiation therapy can be withheld in selected patients with multiple lesions to avoid acute or chronic adverse effects, especially neurocognitive decline, without causing survival disadvantage. In this review, we assessed the evidence for SRS treatment of patients with multiple brain metastases. PMID:26811300

  12. Physician Expectations of Treatment Outcomes for Patients With Brain Metastases Referred for Whole Brain Radiotherapy

    SciTech Connect

    Barnes, Elizabeth A.; Chow, Edward; Tsao, May N.; Bradley, Nicole M.; Doyle, Meagan; Li, Kathy; Lam, Kelvin; Danjoux, Cyril

    2010-01-15

    Purpose: Patients with advanced cancer are referred to our Rapid Response Radiotherapy Program for quick access to palliative radiotherapy. The primary objective of this prospective study was to determine the physician expectations of the treatment outcomes for patients with brain metastases referred for whole brain radiotherapy (WBRT). The secondary objectives were to determine the factors influencing the expectations and to examine the accuracy of the physician-estimated patient survival. Methods and Materials: Patients were identified during a 17-month period. The referring physicians were sent a survey by facsimile to be completed and returned before the patient consultation. Information was sought on the patient's disease status, the physician's expectations of WBRT, the estimated patient survival and performance status, and physician demographic data. Results: A total of 137 surveys were sent out, and the overall response rate was 57.7%. The median patient age was 66 years (range, 35-87), 78.5% had multiple brain metastases, 42.3% had a controlled primary tumor, and 62.3% had extracranial disease. WBRT was thought to stabilize neurologic symptoms, improve quality of life, and allow for a Decadron (dexamethasone) taper by >=94.9% of the referring physicians; 87.0% thought WBRT would improve performance status; 77.9% thought it would improve neurologic symptoms; and 40.8% thought it would improve survival. The referring physicians estimated patient survival as a median of 6.0 months; however, the actual survival was a median of 2.5 months, for a median individual difference of 1.9 months (p < .0001). Conclusion: Physicians referring patients with brain metastases for consideration of WBRT are often overly optimistic when estimating the clinical benefit of the treatment and overestimate patient survival. These findings highlight the need for education and additional research in this field.

  13. Multiple calcified brain metastases in a man with invasive ductal breast cancer.

    PubMed

    Ressl, Nadine; Oberndorfer, Stefan

    2015-01-01

    We report a case of a 52-year-old Caucasian man with invasive ductal carcinoma of the breast. One year after initial diagnosis, he developed a generalised epileptic seizure and neuroimaging showed multiple, calcified intracerebral lesions. Owing to these atypical cerebral imaging findings, comprehensive serological and cerebrospinal fluid analysis was conducted and a latent toxoplasmosis was suspected. In order to distinguish between metastases and an infectious disease, a cerebral biopsy was performed, which verified brain metastases. The patient received whole-brain radiotherapy. The last cerebral CT scan, 18 months later showed stable disease. Calcification of brain metastases in patients with breast cancer is very rare. Owing to their non-characteristic radiological appearance with a lack of contrast enhancement, diagnosis of metastases can be difficult. Infectious diseases should be considered within the diagnostic work up. Owing to possible pitfalls, we recommend a widespread differential diagnostic work up in similar cases, and even in cases with a confirmed primary tumour. PMID:26472289

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

    PubMed Central

    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 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 < 0.001), only 1-3 brain metastases (p = 0.007), no extracerebral metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved survival. Local control rates at 6 and 12 months were 37% and 15%, respectively. In the multivariate analyses, KPS ≥70 (p < 0.001), only 1-3 brain metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved local control. In RPA class 3 patients, survival rates at 6 months were 10% (35 of 39 patients) after 10 × 3 Gy and 9% (2 of 23 patients) after greater doses, respectively (p = 0.98). 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. PMID:20977700

  15. Assessment of prognostic scores in brain metastases from breast cancer

    PubMed Central

    Tabouret, Emeline; Metellus, Philippe; Gonçalves, Anthony; Esterni, Benjamin; Charaffe-Jauffret, Emmanuelle; Viens, Patrice; Tallet, Agnés

    2014-01-01

    Background Breast cancer (BC) is the second most common cause of brain metastases (BM). Optimal management of BM from BC is still debated. In an attempt to provide appropriate treatment and to assist with optimal patient selection, several specific prognostic classifications for BM from BC have been established. We evaluated the prognostic value and validity of the 6 proposed scoring systems in an independent population of BC patients with BM. Methods We retrospectively reviewed all consecutive BC patients referred to our institution for newly diagnosed BM between October 1995 and July 2011 (n = 149). Each of the 6 scores proposed for BM from BC (Sperduto, Niwinska, Park, Nieder, Le Scodan, and Claude) was applied to this population. The discriminative ability of each score was assessed using the Brier score and the C-index. Individual prognostic values of clinical and histological factors were analyzed using uni- and multivariate analyses. Results Median overall survival was 15.1 months (95% CI,11.5–18.7). Sperduto-GPA (P < .001), Nieder (P < .001), Park (P < .001), Claude (P < .001), Niwinska (P < .001), and Le Scodan (P = .034) scores all showed significant prognostic value. The Nieder score showed the best discriminative ability (C-index, 0.672; Brier score error reduction, 16.1%). Conclusion The majority of prognostic scores were relevant for patients with BM from BC in our independent population, and the Nieder score seems to present the best predictive value but showed a relatively low positive predictive value. Thus, these results remain insufficient and challenge the routine use of these scoring systems. PMID:24311640

  16. Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain Metastases

    PubMed Central

    Jakubovic, Raphael; Sahgal, Arjun; Ruschin, Mark; Pejović-Milić, Ana; Milwid, Rachael; Aviv, Richard I.

    2015-01-01

    Purpose: To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). Methods: Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. Results: Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. Conclusion: Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio. PMID:26269612

  17. Stereotactic radiosurgery (SRS) in the modern management of patients with brain metastases

    PubMed Central

    Soliman, Hany; Das, Sunit; Larson, David A.; Sahgal, Arjun

    2016-01-01

    Stereotactic radiosurgery (SRS) is an established non-invasive ablative therapy for brain metastases. Early clinical trials with SRS proved that tumor control rates are superior to whole brain radiotherapy (WBRT) alone. As a result, WBRT plus SRS was widely adopted for patients with a limited number of brain metastases (“limited number” customarily means 1-4). Subsequent trials focused on answering whether WBRT upfront was necessary at all. Based on current randomized controlled trials (RCTs) and meta-analyses comparing SRS alone to SRS plus WBRT, adjuvant WBRT results in better intracranial control; however, at the expense of neurocognitive functioning and quality of life. These adverse effects of WBRT may also negatively impact on survival in younger patients. Based on the results of these studies, treatment has shifted to SRS alone in patients with a limited number of metastases. Additionally, RCTs are evaluating the role of SRS alone in patients with >4 brain metastases. New developments in SRS include fractionated SRS for large tumors and the integration of SRS with targeted systemic therapies that cross the blood brain barrier and/or stimulate an immune response. We present in this review the current high level evidence and rationale supporting SRS as the standard of care for patients with limited brain metastases, and emerging applications of SRS. PMID:26848525

  18. Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases

    PubMed Central

    2011-01-01

    Introduction Activation status of the phosphatidylinositol 3-kinase (PI3K) pathway in breast cancer brain metastases (BCBMs) is largely unknown. We examined expression of phospho(p)-AKT, p-S6, and phosphatase and tensin homologue (PTEN) in BCBMs and their implications for overall survival (OS) and survival after BCBMs. Secondary analyses included PI3K pathway activation status and associations with time to distant recurrence (TTDR) and time to BCBMs. Similar analyses were also conducted among the subset of patients with triple-negative BCBMs. Methods p-AKT, p-S6, and PTEN expression was assessed with immunohistochemistry in 52 BCBMs and 12 matched primary BCs. Subtypes were defined as hormone receptor (HR)+/HER2-, HER2+, and triple-negative (TNBC). Survival analyses were performed by using a Cox model, and survival curves were estimated with the Kaplan-Meier method. Results Expression of p-AKT and p-S6 and lack of PTEN (PTEN-) was observed in 75%, 69%, and 25% of BCBMs. Concordance between primary BCs and matched BCBMs was 67% for p-AKT, 58% for p-S6, and 83% for PTEN. PTEN- was more common in TNBC compared with HR+/HER2- and HER2+. Expression of p-AKT, p-S6, and PTEN- was not associated with OS or survival after BCBMs (all, P > 0.06). Interestingly, among all patients, PTEN- correlated with shorter time to distant and brain recurrence. Among patients with TNBC, PTEN- in BCBMs was associated with poorer overall survival. Conclusions The PI3K pathway is active in most BCBMs regardless of subtype. Inhibition of this pathway represents a promising therapeutic strategy for patients with BCBMs, a group of patients with poor prognosis and limited systemic therapeutic options. Although expression of the PI3K pathway did not correlate with OS and survival after BCBM, PTEN- association with time to recurrence and OS (among patients with TNBC) is worthy of further study. PMID:22132754

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

    PubMed Central

    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

    Background 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. Methods 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. Results 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

  20. [Radiotherapy plus concomitant systemic therapies for patients with brain metastases from breast cancer].

    PubMed

    Cao, K I; Kirova, Y M

    2014-06-01

    The incidence of brain metastases from breast cancer is increasing with diagnosis and therapeutics progress, especially with systemic therapies. The occurrence of multiple brain metastases remains a delicate situation when surgery and stereotactic radiosurgery are not indicated, nor available. Treatment strategy is based on the patient's general condition and extracranial disease status. Whole brain radiation therapy remains the gold standard local treatment but its efficacy is limited with a median overall survival of 6 months. New strategies are needed for increasing survival and patients' quality of life. Combining radiation therapy and chemotherapy has been a subject of interest. This article sums up the different radiotherapy plus concomitant systemic therapies combinations for the treatment of brain metastases from breast cancer. PMID:24731405

  1. miR-20b is up-regulated in brain metastases from primary breast cancers

    PubMed Central

    Ahmad, Aamir; Ginnebaugh, Kevin R.; Sethi, Seema; Chen, Wei; Ali, Rouba; Mittal, Sandeep; Sarkar, Fazlul H.

    2015-01-01

    Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with >50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target. PMID:25893380

  2. It is time to reevaluate the management of patients with brain metastases.

    PubMed

    Kondziolka, Douglas; Kalkanis, Steven N; Mehta, Minesh P; Ahluwalia, Manmeet; Loeffler, Jay S

    2014-07-01

    There are many elements to the science that drives the clinical care of patients with brain metastases. Although part of an understanding that continues to evolve, a number of key historical misconceptions remain that commonly drive physicians' and researchers' attitudes and approaches. By understanding how these relate to current practice, we can better comprehend our available science to provide both better research and care. These past misconceptions include: Misconception 1: Once a primary cancer spreads to the brain, the histology of that primary tumor does not have much impact on response to chemotherapy, sensitivity to radiation, risk of further brain relapse, development of additional metastatic lesions, or survival. All tumor primary histologies are the same once they spread to the brain. They are the same in terms of the number of tumors, radiosensitivity, chemoresponsiveness, risk of further brain relapse, and survival. Misconception 2: The number of brain metastases matters. This number matters in terms of subsequent brain relapse, survival, and cognitive dysfunction; the precise number of metastases can also be used as a limit in determining which patients might be eligible for a particular treatment option. Misconception 3: Cancer in the brain is always a diffuse problem due to the presence of micrometastases. Misconception 4: Whole-brain radiation therapy invariably causes disabling cognitive dysfunction if a patient lives long enough. Misconception 5: Most brain metastases are symptomatic. Thus, it is not worth screening patients for brain metastases, especially because the impact on survival is minimal. The conduct and findings of past clinical research have led to conceptions that affect clinical care yet appear limiting. PMID:24662510

  3. In-vivo longitudinal MRI study: an assessment of melanoma brain metastases in a clinically relevant mouse model.

    PubMed

    Henry, Mariama N; Chen, Yuhua; McFadden, Catherine D; Simedrea, Felicia C; Foster, Paula J

    2015-04-01

    Brain metastases are an important clinical problem. Few animal models exist for melanoma brain metastases; many of which are not clinically relevant. Longitudinal MRI was implemented to examine the development of tumors in a clinically relevant mouse model of melanoma brain metastases. Fifty thousand human metastatic melanoma (A2058) cells were injected intracardially into nude mice. Three Tesla MRI was performed using a custom-built gradient insert coil and a mouse solenoid head coil. Imaging was performed on consecutive days at four time points. Tumor burden and volumes of metastases were measured from balanced steady-state free precession image data. Metastases with a disrupted blood-tumor barrier were identified from T1-weighted spin echo images acquired after administration of gadopentetic acid (Gd-DTPA). Metastases permeable to Gd-DTPA showed signal enhancement. The number of enhancing metastases was determined by comparing balanced steady-state free precession images with T1-weighted spin echo images. After the final imaging session, ex-vivo permeability and histological analyses were carried out. Imaging showed that both enhancing and nonenhancing brain metastases coexist in the brain, and that most metastases switched from the nonenhancing to the enhancing phenotype. Small numbers of brain metastases were enhancing when first detected by MRI and remained enhancing, whereas other metastases remained nonenhancing to Gd-DTPA throughout the experiment. No clear relationship existed between the permeability of brain metastases and size, brain location and age. Longitudinal in-vivo MRI is key to studying the complex and dynamic processes of metastasis and changes in the blood-tumor barrier permeability, which may lead to a better understanding of the variable responses of brain metastases to treatments. PMID:25513779

  4. Differential CD44 expression patterns in primary brain tumours and brain metastases.

    PubMed Central

    Li, H.; Liu, J.; Hofmann, M.; Hamou, M. F.; de Tribolet, N.

    1995-01-01

    Splicing variants of CD44 (CD44v) are increasingly recognised as metastasis-promoting factors in rodent and some human cancers. However, the frequency for CD44v expression in human cancers and their metastases and the status of CD44v expression in low or non-metastatic tumours is still uncertain. To address this issue, we investigated CD44 expression patterns in brain metastases (BMTs) spread from more than ten organs and five types of primary brain tumours (PBTs) by Northern blot, reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemical analysis. The results demonstrated that all of the 56 PBTs examined express standard form of CD44 (CD44s) but none of them express CD44v. In contrast, 22 of 26 BMTs studied were found with CD44v expression. Our data thus present direct evidence of a general distribution of CD44 in BMTs but suggest that such expression is an extremely rare event in PBTs. Therefore, the presence or absence of CD44v expression may be related to high or low metastatic potential of human malignancies. Images Figure 2 Figure 1 PMID:7541233

  5. Differential Impact of Whole-Brain Radiotherapy Added to Radiosurgery for Brain Metastases

    SciTech Connect

    Kong, Doo-Sik; Lee, Jung-Il; Im, Yong-Seok; Nam, Do-Hyun; Park, Kwan; Kim, Jong-Hyun

    2010-10-01

    Purpose: The authors investigated whether the addition of whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) provided any therapeutic benefit according to recursive partitioning analysis (RPA) class. Methods and Materials: Two hundred forty-five patients with 1 to 10 metastases who underwent SRS between January 2002 and December 2007 were included in the study. Of those, 168 patients were treated with SRS alone and 77 patients received SRS followed by WBRT. Actuarial curves were estimated using the Kaplan-Meier method regarding overall survival (OS), distant brain control (DC), and local brain control (LC) stratified by RPA class. Analyses for known prognostic variables were performed using the Cox proportional hazards model. Results: Univariate and multivariate analysis revealed that control of the primary tumor, small number of brain metastases, Karnofsky performance scale (KPS) > 70, and initial treatment modalities were significant predictors for survival. For RPA class 1, SRS plus WBRT was associated with a longer survival time compared with SRS alone (854 days vs. 426 days, p = 0.042). The SRS plus WBRT group also showed better LC rate than did the SRS-alone group (p = 0.021), although they did not show a better DC rate (p = 0.079). By contrast, for RPA class 2 or 3, no significant difference in OS, LC, or DC was found between the two groups. Conclusions: These results suggest that RPA classification should determine whether or not WBRT is added to SRS. WBRT may be recommended to be added to SRS for patients in whom long-term survival is expected on the basis of RPA classification.

  6. Identification of primary tumors of brain metastases by SIMCA classification of IR spectroscopic images.

    PubMed

    Krafft, Christoph; Shapoval, Larysa; Sobottka, Stephan B; Geiger, Kathrin D; Schackert, Gabriele; Salzer, Reiner

    2006-07-01

    Brain metastases are secondary intracranial lesions which occur more frequently than primary brain tumors. The four most abundant types of brain metastasis originate from primary tumors of lung cancer, colorectal cancer, breast cancer and renal cell carcinoma. As metastatic cells contain the molecular information of the primary tissue cells and IR spectroscopy probes the molecular fingerprint of cells, IR spectroscopy based methods constitute a new approach to determine the origin of brain metastases. IR spectroscopic images of 4 by 4 mm2 tissue areas were recorded in transmission mode by a FTIR imaging spectrometer coupled to a focal plane array detector. Unsupervised cluster analysis revealed variances within each cryosection. Selected clusters of five IR images with known diagnoses trained a supervised classification model based on the algorithm soft independent modeling of class analogies (SIMCA). This model was applied to distinguish normal brain tissue from brain metastases and to identify the primary tumor of brain metastases in 15 independent IR images. All specimens were assigned to the correct tissue class. This proof-of-concept study demonstrates that IR spectroscopy can complement established methods such as histopathology or immunohistochemistry for diagnosis. PMID:16787638

  7. A Multi-institutional Study of Factors Influencing the Use of Stereotactic Radiosurgery for Brain Metastases

    SciTech Connect

    Hodgson, David C.; Charpentier, Anne-Marie; Cigsar, Candemir; Atenafu, Eshetu G.; Ng, Angela; Bahl, Guarav; Zadeh, Gelareh; San Miguel, John; Menard, Cynthia

    2013-02-01

    Purpose: Stereotactic radiosurgery (SRS) for brain metastases is a relatively well-studied technology with established guidelines regarding patient selection, although its implementation is technically complex. We evaluated the extent to which local availability of SRS affected the treatment of patients with brain metastases. Methods and Materials: We identified 3030 patients who received whole-brain radiation therapy (WBRT) for brain metastases in 1 of 7 cancer centers in Ontario. Clinical data were abstracted for a random sample of 973 patients. Logistic regression analyses were performed to identify factors associated with the use of SRS as a boost within 4 months following WBRT or at any time following WBRT. Results: Of 898 patients eligible for analysis, SRS was provided to 70 (7.8%) patients at some time during the course of their disease and to 34 (3.8%) patients as a boost following WBRT. In multivariable analyses, factors significantly associated with the use of SRS boost following WBRT were fewer brain metastases (odds ratio [OR] = 6.50), controlled extracranial disease (OR = 3.49), age (OR = 0.97 per year of advancing age), and the presence of an on-site SRS program at the hospital where WBRT was given (OR = 12.34; all P values were <.05). Similarly, availability of on-site SRS was the factor most predictive of the use of SRS at any time following WBRT (OR = 5.98). Among patients with 1-3 brain metastases, good/fair performance status, and no evidence of active extracranial disease, SRS was provided to 40.3% of patients who received WBRT in a hospital that had an on-site SRS program vs 3.0% of patients who received WBRT at a hospital without SRS (P<.01). Conclusions: The availability of on-site SRS is the factor most strongly associated with the provision of this treatment to patients with brain metastases and appears to be more influential than accepted clinical eligibility factors.

  8. Distribution of Brain Metastases in Relation to the Hippocampus: Implications for Neurocognitive Functional Preservation

    SciTech Connect

    Ghia, Amol; Tome, Wolfgang A.; Thomas, Sayana; Cannon, George; Khuntia, Deepak; Kuo, John S.; Mehta, Minesh P. . E-mail: mehta@humonc.wisc.edu

    2007-07-15

    Purpose: With the advent of intensity-modulated radiotherapy, the ability to limit the radiation dose to normal tissue offers an avenue to limit side effects. This study attempted to delineate the distribution of brain metastases with relation to the hippocampus for the purpose of exploring the viability of tomotherapy-guided hippocampal sparing therapy potentially to reduce neurocognitive deficits from radiation. Methods and Materials: The pre-radiotherapy T1-weighted, postcontrast axial MR images of 100 patients who received whole brain radiotherapy, stereotactic radiosurgery, or a radiosurgical boost following whole brain radiotherapy between 2002 and 2006 were examined. We contoured brain metastases as well as hippocampi with 5-, 10-, and 15-mm expansion envelopes. Results: Of the 272 identified metastases, 3.3% (n = 9) were within 5 mm of the hippocampus, and 86.4% of metastases were greater than 15 mm from the hippocampus (n = 235). The most common location for metastatic disease was the frontal lobe (31.6%, n = 86). This was followed by the cerebellum (24.3%, n = 66), parietal lobe (16.9%, n = 46), temporal lobe (12.9%, n = 35), occipital lobe (7.7%, n = 21), deep brain nuclei (4.0%, n = 11), and brainstem (2.6%, n = 7). Conclusions: Of the 100 patients, 8 had metastases within 5 mm of the hippocampus. Hence, a 5-mm margin around the hippocampus for conformal avoidance whole brain radiotherapy represents an acceptable risk, especially because these patients in the absence of any other intracranial disease could be salvaged using stereotactic radiosurgery. Moreover, we developed a hippocampal sparing tomotherapy plan as proof of principle to verify the feasibility of this therapy in the setting of brain metastases.

  9. βIII-Tubulin Regulates Breast Cancer Metastases to the Brain

    PubMed Central

    Kanojia, Deepak; Morshed, Ramin A.; Zhang, Lingjiao; Miska, Jason M.; Qiao, Jian; Kim, Julius W.; Pytel, Peter; Balyasnikova, Irina V.; Lesniak, Maciej S.; Ahmed, Atique U.

    2015-01-01

    Brain metastases occur in about 10–30% of breast cancer patients, which culminates in a poor prognosis. It is therefore critical to understand the molecular mechanisms underlying brain metastatic processes to identify relevant targets. We hypothesized that breast cancer cells must express brain-associated markers that would enable their invasion and survival in the brain microenvironment. We assessed a panel of brain-predominant markers and found an elevation of several neuronal markers (βIII tubulin, Nestin and AchE) in brain metastatic breast cancer cells. Among these neuronal predominant markers, in silico analysis revealed overexpression of βIII tubulin (TUBB3) in breast cancer brain metastases (BCBM) and its expression was significantly associated with distant metastases. TUBB3 knockdown studies were conducted in breast cancer models (MDA-Br, GLIM2 and MDA-MB-468) which revealed significant reduction in their invasive capabilities. MDA-Br cells with suppressed TUBB3 also demonstrated loss of key signaling molecules such as β3 integrin, pFAK, and pSrc in vitro. Furthermore, TUBB3 knockdown in a brain metastatic breast cancer cell line compromised its metastatic ability in vivo, and significantly improved survival in a brain metastasis model. These results implicate a critical role of TUBB3 in conferring brain metastatic potential to breast cancer cells. PMID:25724666

  10. βIII-Tubulin Regulates Breast Cancer Metastases to the Brain.

    PubMed

    Kanojia, Deepak; Morshed, Ramin A; Zhang, Lingjiao; Miska, Jason M; Qiao, Jian; Kim, Julius W; Pytel, Peter; Balyasnikova, Irina V; Lesniak, Maciej S; Ahmed, Atique U

    2015-05-01

    Brain metastases occur in about 10% to 30% of breast cancer patients, which culminates in a poor prognosis. It is, therefore, critical to understand the molecular mechanisms underlying brain metastatic processes to identify relevant targets. We hypothesized that breast cancer cells must express brain-associated markers that would enable their invasion and survival in the brain microenvironment. We assessed a panel of brain-predominant markers and found an elevation of several neuronal markers (βIII-tubulin, Nestin, and AchE) in brain metastatic breast cancer cells. Among these neuronal predominant markers, in silico analysis revealed overexpression of βIII-tubulin (TUBB3) in breast cancer brain metastases (BCBM) and its expression was significantly associated with distant metastases. TUBB3 knockdown studies were conducted in breast cancer models (MDA-Br, GLIM2, and MDA-MB-468), which revealed significant reduction in their invasive capabilities. MDA-Br cells with suppressed TUBB3 also demonstrated loss of key signaling molecules such as β3 integrin, pFAK, and pSrc in vitro. Furthermore, TUBB3 knockdown in a brain metastatic breast cancer cell line compromised its metastatic ability in vivo, and significantly improved survival in a brain metastasis model. These results implicate a critical role of TUBB3 in conferring brain metastatic potential to breast cancer cells. PMID:25724666

  11. Whole brain reirradiation and concurrent temozolomide in patients with brain metastases.

    PubMed

    Minniti, Giuseppe; Scaringi, Claudia; Lanzetta, Gaetano; Bozzao, Alessandro; Romano, Andrea; De Sanctis, Vitaliana; Valeriani, Maurizio; Osti, Mattia; Enrici, Riccardo Maurizi

    2014-06-01

    A second course of whole brain radiation therapy (WBRT) has been employed in selected patients with progressive brain metastases providing favorable symptomatic palliation with acceptable toxicity, although its efficacy and safety remain matter of debate. In the present study we have evaluated the outcomes in patients with progressive intracranial disease treated with WBRT reirradiation and concurrent temozolomide between October 2010 and May 2013. Data were obtained from a prospectively maintained database including patients with brain tumors treated with radiotherapy at Sant'Andrea Hospital. We identified 27 patients (10 males and 17 females) with a median age of 54 years who received WBRT reirradiation at a dose of 25 Gy in ten fractions plus concomitant daily temozolomide administered orally at a dose of 75 mg/m(2). At the time of repeat WBRT all patients had a KPS ≥ 60. The primary disease sites were lung (n = 18) and breast (n = 9). The median overall survival after the second course of WBRT was 6.2 months and the median time to progression was 5.5 months. Eight patients experienced complete resolution of symptoms, 9 patients had a significant improvement, and 6 patients had no change in their neurologic function. Four patients had further deterioration after reirradiation. Overall, 85 % of patients improved or maintained their neurologic status. No severe acute toxicity during or after the second course of WBRT reirradiation was observed. On multivariate analysis with the Cox proportional hazards model, stable or absent extracranial metastases (p = 0.005) and response to treatment (p = 0.01) were independent favorable prognostic factors for survival. The median and 12-month survival rates were 12 months and 50 % in patients with stable or absent extracranial disease and 4.6 months and 7 % in those with progressive extracranial disease (p = 0.001). In conclusion, in the respect to the small number of treated patients, repeat WBRT plus concomitant

  12. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis

    PubMed Central

    2011-01-01

    Purpose to investigate the factors affecting survival and toxicity in patients treated with stereotactic radiosurgery (SRS), with special attention to volumes of brain receiving a specific dose (V10 - V16 Gy) as predictors for brain radionecrosis. Patients and Methods Two hundred six consecutive patients with 310 cerebral metastases less than 3.5 cm were treated with SRS as primary treatment and followed prospectively at University of Rome La Sapienza Sant'Andrea Hospital. Overall survival, brain control, and local control were estimated using the Kaplan-Meier method calculated from the time of SRS. Univariate and multivariate analysis using a Cox proportional hazards regression model were performed to determine the predictive value of prognostic factors for treatment outcome and SRS-related complications. Results Median overall survival and brain control were 14.1 months and 10 months, respectively. The 1-year and 2-year survival rates were 58% and 24%, and respective brain control were 43% and 22%. Sixteen patients recurred locally after SRS, with 1-year and 2-year local control rates of 92% and 84%, respectively. On multivariate analysis, stable extracranial disease and KPS >70 were associated with the most significant survival benefit. Neurological complications were recorded in 27 (13%) patients. Severe neurological complications (RTOG Grade 3 and 4) occurred in 5.8% of patients. Brain radionecrosis occurred in 24% of treated lesions, being symptomatic in 10% and asymptomatic in 14%. On multivariate analysis, V10 through V16 Gy were independent risk factors for radionecrosis, with V10 Gy and V12 Gy being the most predictive (p = 0.0001). For V10 Gy >12.6 cm3 and V12 Gy >10.9 cm3 the risk of radionecrosis was 47%. Conclusions SRS alone represents a feasible option as initial treatment for patients with brain metastases, however a significant subset of patients may develop neurological complications. Lesions with V12 Gy >8.5 cm3 carries a risk of radionecrosis

  13. A planning study of simultaneous integrated boost with forward IMRT for multiple brain metastases

    SciTech Connect

    Liang, Xiaodong; Ni, Lingqin; Hu, Wei; Chen, Weijun; Ying, Shenpeng; Gong, Qiangjun; Liu, Yanmei

    2013-07-01

    The objective of this study was to evaluate the dose conformity and feasibility of whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in patients with 1 to 3 brain metastases. Forward intensity-modulated radiation therapy plans were generated for 10 patients with 1 to 3 brain metastases on Pinnacle 6.2 Treatment Planning System. The prescribed dose was 30 Gy to the whole brain (planning target volume [PTV]{sub wbrt}) and 40 Gy to individual brain metastases (PTV{sub boost}) simultaneously, and both doses were given in 10 fractions. The maximum diameters of individual brain metastases ranged from 1.6 to 6 cm, and the summated PTVs per patient ranged from 1.62 to 69.81 cm{sup 3}. Conformity and feasibility were evaluated regarding conformation number and treatment delivery time. One hundred percent volume of the PTV{sub boost} received at least 95% of the prescribed dose in all cases. The maximum doses were less than 110% of the prescribed dose to the PTV{sub boost}, and all of the hot spots were within the PTV{sub boost}. The volume of the PTV{sub wbrt} that received at least 95% of the prescribed dose ranged from 99.2% to 100%. The mean values of conformation number were 0.682. The mean treatment delivery time was 2.79 minutes. Ten beams were used on an average in these plans. Whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in 1 to 3 brain metastases is feasible, and treatment delivery time is short.

  14. Unusual Adrenal and Brain Metastases From Follicular Thyroid Carcinoma Revealed by 131I SPECT/CT.

    PubMed

    Zhao, Zhen; Shen, Guo-hua; Liu, Bin; Kuang, An-ren

    2016-01-01

    The adrenal metastasis from differentiated thyroid carcinoma is uncommon. Metastatic involvement of both adrenal and brain in the same patient from differentiated thyroid carcinoma is rare. Here, we described an unusual case with iodine-avid lung, bone, adrenal, liver, and brain metastases from follicular thyroid carcinoma confirmed by 131I SPECT/CT. The utilization of SPECT/CT in thyroid cancer patients can detect the presence of metastases and also exclude potential false-positive lesions. Our case demonstrates that SPECT/CT is helpful in localizing and confirming metastatic lesions from differentiated thyroid carcinoma in rare and unusual sites. PMID:26018699

  15. Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience.

    PubMed

    Madajewicz, S; Karakousis, C; West, C R; Caracandas, J; Avellanosa, A M

    1984-06-01

    One-hundred twenty five of 700 patients with malignant melanoma treated at Roswell Park Memorial Institute from 1972 to 1978 were found to have brain metastases. Seventy-three percent of the patients had multiple brain metastases. Male to female ratio was 1.9:1. The median survival of the untreated group of patients was 3 weeks as compared with that of 6 weeks for the patients maintained on steroids only, 9 weeks for those who received radiotherapy, 11 weeks for the patients treated with intraarterial chemotherapy, and 26 weeks for the patients who underwent successful surgical excision of a solitary lesion. PMID:6713349

  16. Surgery and radiation therapy for brain metastases from classic biphasic pulmonary blastoma

    PubMed Central

    Kawasaki, Kenta; Yamamoto, Kuniatsu; Suzuki, Yoshio; Saito, Hirohisa

    2014-01-01

    Pulmonary blastoma, a rare malignant lung tumour, can metastasise to the brain. However, there is no evidence for any effective treatment. The aim of this report is to discuss the treatment options for pulmonary blastoma and confirm the necessity for a pathological diagnosis. A 75-year-old man was admitted with progressive right-sided hemiplegia and aphasia. MRI showed multiple brain tumours. A left frontal lobe lesion was surgically resected, after which he underwent whole brain radiation (30 Gy/10 fractions). He died of an acute exacerbation of interstitial pneumonia. On performing autopsy, partial responses in the brain metastases that had been irradiated were confirmed pathologically. Thus, we present pathological confirmation that surgery and radiation therapy have therapeutic effects on brain metastases from pulmonary blastoma. PMID:24895392

  17. Tumor Directed, Scalp Sparing Intensity Modulated Whole Brain Radiotherapy for Brain Metastases.

    PubMed

    Kao, Johnny; Darakchiev, Boramir; Conboy, Linda; Ogurek, Sara; Sharma, Neha; Ren, Xuemin; Pettit, Jeffrey

    2015-10-01

    Despite significant technical advances in radiation delivery, conventional whole brain radiation therapy (WBRT) has not materially changed in the past 50 years. We hypothesized that IMRT can selectively spare uninvolved brain and scalp with the goal of reducing acute and late toxicity. MRI/CT simulation image registration was performed. We performed IMRT planning to simultaneously treat the brain tumor(s) on MRI + 5 mm margin to 37.5 Gy in 15 fractions while limiting the uninvolved brain + 2 mm margin to 30 Gy in 15 fractions and the mean scalp dose to #18 Gy. Three field IMRT plans were compared to conventional WBRT plans. Symptomatic patients were started on conventional WBRT for 2 to 3 fractions while IMRT planning was performed. Seventeen consecutive patients with brain metastases with RPA class I and II disease with no leptomeningeal spread were treated with IMRT WBRT. Compared to conventional WBRT, IMRT reduced the mean scalp dose (26.2 Gy vs. 16.4 Gy, p < 0.001) and the mean PTV30 dose (38.4 Gy vs. 32.0 Gy, p < 0.001) while achieving similar mean PTV37.5 doses (38.3 Gy vs. 38.0 Gy, p = 0.26). Using Olsen hair loss score criteria, 4 of 15 assessable patients preserved at least 50% of hair coverage at 1 to 3 months after treatment while 6 patients preserved between 25 and 50% hair coverage. At a median follow-up of 6.8 months (range: 5 to 15 months), the median overall survival was 5.4 months. Four patients relapsed within the brain, one within the PTV37.5 and three outside the PTV37.5. Tumor directed, scalp sparing IMRT is feasible, achieves rational dose distributions and preserves partial hair coverage in the majority of patients. Further studies are warranted to determine whether the increased utilization of resources needed for IMRT are appropriate in this setting. PMID:24750002

  18. New Breast Cancer Recursive Partitioning Analysis Prognostic Index in Patients With Newly Diagnosed Brain Metastases

    SciTech Connect

    Niwinska, Anna; Murawska, Magdalena

    2012-04-01

    Purpose: The aim of the study was to present a new breast cancer recursive partitioning analysis (RPA) prognostic index for patients with newly diagnosed brain metastases as a guide in clinical decision making. Methods and Materials: A prospectively collected group of 441 consecutive patients with breast cancer and brain metastases treated between the years 2003 and 2009 was assessed. Prognostic factors significant for univariate analysis were included into RPA. Results: Three prognostic classes of a new breast cancer RPA prognostic index were selected. The median survival of patients within prognostic Classes I, II, and III was 29, 9, and 2.4 months, respectively (p < 0.0001). Class I included patients with one or two brain metastases, without extracranial disease or with controlled extracranial disease, and with Karnofsky performance status (KPS) of 100. Class III included patients with multiple brain metastases with KPS of {<=}60. Class II included all other cases. Conclusions: The breast cancer RPA prognostic index is an easy and valuable tool for use in clinical practice. It can select patients who require aggressive treatment and those in whom whole-brain radiotherapy or symptomatic therapy is the most reasonable option. An individual approach is required for patients from prognostic Class II.

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

    SciTech Connect

    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.

  20. Isolated brain metastases as first site of recurrence in prostate cancer: case report and review of the literature

    PubMed Central

    Craig, J.; Woulfe, J.; Sinclair, J.; Malone, S.

    2015-01-01

    Fewer than 2% of patients with metastatic prostate cancer (pca) develop brain metastases. Autopsy series have confirmed the rarity of brain metastases. When present, brain metastases occur in end stage, once the pca is castrate-resistant and spread to other sites is extensive. Here, we present a rare case of a patient with pca who developed a solitary parenchymal brain metastasis as first site of relapse 9 years after radical therapy. The patient underwent craniotomy and excision of the tumour. A second recurrence was also isolated to the brain. In the literature, pca patients with brain metastases have a poor mean survival of 1–7.6 months. The patient in our case report experienced a relatively favourable outcome, surviving 19 months after his initial brain relapse. PMID:26715888

  1. Clear cell renal cell carcinoma with vaginal and brain metastases: a case report and literature review

    PubMed Central

    Momah, Tobe; Dhanan, Etwaru; Xiao, Phillip; Kondamudi, Vasantha

    2009-01-01

    There are very few cases of clear cell renal cell carcinoma with metastases to the vagina and brain reported in the literature. Our case study highlights this rare clinical occurrence and its associated complications including pulmonary embolism. In addition we discuss current management guidelines for treating and diagnosing the disease, and how this management improves prognosis.

  2. Current treatment options of brain metastases and outcomes in patients with malignant melanoma.

    PubMed

    Nowak-Sadzikowska, Jadwiga; Walasek, Tomasz; Jakubowicz, Jerzy; Blecharz, Paweł; Reinfuss, Marian

    2016-01-01

    The prognosis for patients with melanoma who have brain metastases is poor, a median survival does not exceed 4-6 months. There are no uniform standards of treatment for patients with melanoma brain metastases (MBMs). The most preferred treatment approaches include local therapy - surgical resection and/or stereotactic radiosurgery (SRS). The role of whole brain radiotherapy (WBRT) as an adjuvant to local therapy is controversial. WBRT remains a palliative approach for those patients who have multiple MBMs with contraindications for surgery or SRS, or/and poor performance status, or/and very widespread extracranial metastases. Corticosteroids have been used in palliative treatment of MBMs as relief from symptoms related to intracranial pressure and edema. In recent years, the development of new systemic therapeutic strategies has been observed. Various modalities of systemic treatment include chemotherapy, immunotherapy and targeted therapy. Also, multimodality management in different combinations is a common strategy. Decisions regarding the use of specific treatment modalities are dependent on patient's performance status, and the extent of both intracranial and extracranial disease. This review summarizes current treatment options, indications and outcomes in patients with brain metastases from melanoma. PMID:27601961

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

    SciTech Connect

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

    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

  4. Identification of primary tumors of brain metastases by infrared spectroscopic imaging and linear discriminant analysis.

    PubMed

    Krafft, Christoph; Shapoval, Larysa; Sobottka, Stephan B; Schackert, Gabriele; Salzer, Reiner

    2006-06-01

    This study applies infrared (IR) spectroscopy to distinguish normal brain tissue from brain metastases and to determine the primary tumor of four frequent brain metastases such as lung cancer, colorectal cancer, breast cancer, and renal cell carcinoma. Standard methods sometimes fail to identify the origin of brain metastases. As metastatic cells contain the molecular information of the primary tissue cells and IR spectroscopy probes the molecular fingerprint of cells, IR spectroscopy based methods constitute a new approach to determine the primary tumor of a brain metastasis. IR spectroscopic images were recorded by a FTIR spectrometer equipped with a macro sample chamber and coupled to a focal plane array detector. Unsupervised cluster analysis of IR images revealed variances within each sample and between samples of the same tissue type. Cluster averaged IR spectra of tissue classes with known diagnoses were selected to develop a metric with eight variables. These data trained a supervised classification model based on linear discriminant analysis that was used to identify the origin of 20 cryosections including one brain metastasis with an unknown primary tumor. PMID:16700626

  5. Comparison of Two Therapeutic Strategies in Patients With Non-squamous Non-small Cell Lung Cancer (NSCLC) With Asymptomatic Brain Metastases

    ClinicalTrials.gov

    2015-11-29

    Non-small Cell Lung Cancer Metastatic; Non Epidermoid; Non-small Cell Lung Cancer; Adenocarcinoma of Lung Metastatic to Brain; Cerebral Metastases; Cerebral Radiotherapy; Brain Radiotherapy; Bevacizumab

  6. Emerging strategies for treating brain metastases from breast cancer

    PubMed Central

    Kodack, David P.; Askoxylakis, Vasileios; Ferraro, Gino B.; Fukumura, Dai; Jain, Rakesh K.

    2015-01-01

    Summary Brain metastasis is an end stage in breast cancer progression. Traditional treatment options have minimal efficacy, and overall survival is on the order of months. The incidence of brain metastatic disease is increasing with the improved management of systemic disease and prolongation of survival. Unfortunately, the targeted therapies that control systemic disease have diminished efficacy against brain lesions. There are reasons to be optimistic, however, as emerging therapies have shown promise in preclinical and early clinical settings. This review discusses recent advances in breast cancer brain metastasis therapy and potential approaches for successful treatment. PMID:25670078

  7. Lapatinib plus capecitabine resolved human epidermal growth factor receptor 2-positive brain metastases.

    PubMed

    Glück, Stefan; Castrellon, Aurelio

    2009-01-01

    Brain metastases affect 25%-30% of women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and are associated with a high burden of disease and poor prognosis. A 55-year-old woman presented with HER2-positive, hormone receptor-positive, locally advanced infiltrating ductal carcinoma. She received 4 cycles of neoadjuvant docetaxel (75 mg/m) plus trastuzumab (6 mg/kg) on a 21-day cycle, resulting in complete pathologic response at the time of surgery. Trastuzumab (6 mg/kg every 21 days) plus anastrozole (1 mg/d) was continued for 1 year. Two years later, the patient progressed with pulmonary nodules and a large pleural effusion. Computed tomography and positron emission tomography revealed multiple lesions in the liver and thoracic spine but no evidence of brain metastases. The patient received weekly trastuzumab (2 mg/kg), paclitaxel (80 mg/m), and carboplatin (area under the curve 2) for 6 months; her symptoms resolved and her disease stabilized. Seven months later, she developed diplopia and gait difficulties, and magnetic resonance imaging revealed multiple brain lesions. Whole-brain radiotherapy (30 Gy in 10 fractions) was delivered with excellent clinical results. The patient remained progression free without symptoms for approximately 3 months. When she developed central nervous system symptoms, she was treated with lapatinib (1250 mg/d continuously) plus capecitabine (2000 mg/m given on days 1-14 of a 21-day cycle). Four months later, a brain computed tomography performed shortly before her death from progressive systemic disease revealed near complete resolution of brain metastases. Lapatinib plus capecitabine seems to have clinical activity in HER2-positive brain metastases. PMID:19287304

  8. Long-term survival in a patient with brain metastases of papillary thyroid carcinoma.

    PubMed

    Guelho, Daniela; Ribeiro, Cristina; Melo, Miguel; Carrilho, Francisco

    2016-01-01

    We present the case of a 43-year-old woman who underwent total thyroidectomy with bilateral lymphadenectomy for a papillary thyroid carcinoma (PTC), solid variant (T4bN1bMx), with V600E BRAF mutation. After ablative therapy, she presented undetectable thyroglobulin (Tg) but progressively increasing anti-Tg antibodies (TgAbs). During follow-up, nodal, lung and brain metastases were identified. She was submitted to surgical excision of lung lesions, radiosurgery of brain metastases and five radioiodine treatments. The latest brain MRI showed no lesions, pulmonary CT showed stable micronodules and there was progressive reduction in TgAbs. This is a peculiar case of a PTC with lung and brain metastatic lesions detected through TgAbs. Initial histological and molecular study suggested a more aggressive clinical behaviour, which was eventually confirmed. Although PTC brain metastases are extremely rare and present poor prognosis, our patient presented a good response to treatment and longer survival than usually reported for similar cases. PMID:26961557

  9. Uptake of ANG1005, a Novel Paclitaxel Derivative, Through the Blood-Brain Barrier into Brain and Experimental Brain Metastases of Breast Cancer

    PubMed Central

    Thomas, Fancy C.; Taskar, Kunal; Rudraraju, Vinay; Goda, Satyanarayana; Thorsheim, Helen R.; Gaasch, Julie A.; Palmieri, Diane; Steeg, Patricia S.; Lockman, Paul R.; Smith, Quentin R.

    2010-01-01

    Purpose We evaluated the uptake of angiopep-2 paclitaxel conjugate, ANG1005, into brain and brain metastases of breast cancer in rodents. Most anticancer drugs show poor delivery to brain tumors due to limited transport across the blood-brain barrier (BBB). To overcome this, a 19-amino acid peptide (angiopep-2) was developed that binds to low density lipoprotein receptor-related protein (LRP) receptors at the BBB and has the potential to deliver drugs to brain by receptor-mediated transport. Methods The transfer coefficient (Kin) for brain influx was measured by in situ rat brain perfusion. Drug distribution was determined at 30 min after i.v. injection in mice bearing intracerebral MDA-MB-231BR metastases of breast cancer. Results The BBB Kin for 125I-ANG1005 uptake (7.3 ± 0.2 × 10−3 mL/s/g) exceeded that for 3H-paclitaxel (8.5 ± 0.5 × 10−5) by 86 fold. Over 70% of 125I-ANG1005 tracer stayed in brain after capillary depletion or vascular washout. Brain 125I-ANG1005 uptake was reduced by unlabeled angiopep-2 vector and by LRP ligands, consistent with receptor transport. In vivo uptake of 125I-ANG1005 into vascularly corrected brain and brain metastases exceeded that of 14C-paclitaxel by 4–54 fold. Conclusions The results demonstrate that ANG1005 shows significantly improved delivery to brain and brain metastases of breast cancer compared to free paclitaxel. PMID:19774344

  10. ACR Appropriateness Criteria® Pre-Irradiation Evaluation and Management of Brain Metastases

    PubMed Central

    Gore, Elizabeth M.; Bradley, Jeffrey D.; Buatti, John M.; Germano, Isabelle; Ghafoori, A. Paiman; Henderson, Mark A.; Murad, Gregory J.A.; Patchell, Roy A.; Patel, Samir H.; Robbins, Jared R.; Robins, H. Ian; Vassil, Andrew D.; Wippold, Franz J.; Yunes, Michael J.; Videtic, Gregory M.M.

    2014-01-01

    Abstract Pretreatment evaluation is performed to determine the number, location, and size of the brain metastases and magnetic resonance imaging (MRI) is the recommended imaging technique, particularly in patients being considered for surgery or stereotactic radiosurgery. A contiguous thin-cut volumetric MRI with gadolinium with newer gadolinium-based agents can improve detection of small brain metastases. A systemic workup and medical evaluation are important, given that subsequent treatment for the brain metastases will also depend on the extent of the extracranial disease and on the age and performance status of the patient. Patients with hydrocephalus or impending brain herniation should be started on high doses of corticosteroids and evaluated for possible neurosurgical intervention. Patients with moderate symptoms should receive approximately 4–8 mg/d of dexamethasone in divided doses. The routine use of corticosteroids in patients without neurologic symptoms is not necessary. There is no proven benefit of anticonvulsants in patient without seizures. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID:24971478

  11. Feasibility, safety, and outcome of frameless image-guided robotic radiosurgery for brain metastases.

    PubMed

    Muacevic, Alexander; Kufeld, Markus; Wowra, Berndt; Kreth, Friedrich-Wilhelm; Tonn, Jörg-Christian

    2010-04-01

    We prospectively analyzed the safety and outcome of frameless image-guided robotic stereotactic radiosurgery (SRS) for treatment of brain metastases in patients that would have otherwise been treated with frame-based techniques. During a three-year period, 333 patients with 783 brain metastases of various histologies underwent 391 outpatient SRS procedures. Fifty-five percent of patients had multiple brain metastases. The median (mean) tumor volume was 1.0 cc (2.7 cc). The mean prescribed tumor dose was 18.5 Gy (+/-1.3 Gy). Local/distant tumor recurrences were treated by additional SRS for patients with stable systemic disease. Survival and freedom from local tumor recurrence was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. System accuracy tests (end-to-end tests) were performed with a standard head phantom. Overall median survival was 12.2 months after SRS. The actuarial one-year local control rate was 95.2% (95% CI: 92.0-97.2); the distant brain tumor control rate was 67% (95% CI: 61.0-71.2). Most patients died from systemically progressing cancer (69%). A Karnofsky performance score (KPS) > 70 was related to prolonged survival in the univariate and multivariate analysis. Recursive partition analysis (RPA) classes I and II were related to prolonged survival in the univariate analysis. Twenty-one patients (6.3%) developed treatment-related neurotoxic effects; no patient died because of complications of SRS. Forty-five end-to-end tests documented a mean targeting accuracy of 0.48 +/- 0.22 mm. Single-session, frameless robotic SRS is feasible, accurate, and safe in selected patients with brain metastases of various primary tumors. There seems to be no difference in patient selection, adverse effects, treatment outcomes, or system accuracy compared with frame-based SRS. PMID:19802718

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

    SciTech Connect

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

    2010-04-15

    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.

  13. CyberKnife therapy of 24 multiple brain metastases from lung cancer: A case report

    PubMed Central

    YANG, GUIQING; WANG, YISHAN; WANG, YUANYUAN; LIN, SIXIANG; SUN, DONGNING

    2013-01-01

    Brain metastasis is a significant cause of morbidity and mortality and a critical complication of non-central nervous system primary carcinoma. The present study describes the clinical case of a 46-year-old male with lung cancer and life-threatening brain metastases. The patient was diagnosed with lung cancer with a clinical stage of T2N0M1 (stage IV). Six months after the initial diagnosis and administration of conformal radiotherapy combined with three cycles of chemotherapy, an enhanced computed tomography (CT) scan of the brain revealed abnormalities with double-dosing of intravenous contrast. The CT scan identified >24 lesions scattered in the whole brain. The patient was treated with three-fraction Cyberknife radiotherapy at 22 Gy, delivered to the brain metastases at the Center for Tumor Treatment of People’s Liberation Army 107th Hospital. Following CyberKnife therapy, a CT scan of the brain revealed that most of the tumors had disappeared with almost no residual traces. The stereotactic radiosurgery (SRS) conducted using CyberKnife, an image-guided frameless robotic technology for whole-body radiosurgery, had produced a marked response. The present case report demonstrates that CyberKnife therapy plays a significant role in the management of multiple meta-static brain tumors. PMID:24137362

  14. Surgical Brain Metastases: Management and Outcome Related to Prognostic Indexes: A Critical Review of a Ten-Year Series

    PubMed Central

    Caroli, Manuela; Di Cristofori, Andrea; Lucarella, Francesca; Raneri, Fabio Angelo; Portaluri, Francesco; Gaini, Sergio Maria

    2011-01-01

    Brain metastasis are the most common neoplastic lesions of the nervous system. Many cancer patients are diagnosed on the basis of a first clinical presentation of cancer on the basis of a single or multiple brain lesions. Brain metastases are manifestations of primary disease progression and often determine a poor prognosis. Not all patients with a brain metastases undergo surgery: many are submitted to alternative or palliative treatments. Management of patients with brain metastases is still controversial, and many studies have been developed to determine which is the best therapy. Furthermore, management of patients operated for a brain metastasis is often difficult. Chemotherapy, stereotactic radiosurgery, panencephalic radiation therapy, and surgery, in combination or alone, are the means most commonly used. We report our experience in the management of a ten-year series of surgical brain metastasis and discuss our results in the preoperative and postoperative management of this complex condition. PMID:22084749

  15. O7.02RADIOSURGERY AND BRAIN METASTASES: ADEQUATE SEQUENCE OF BRAIN MRI CAN SIGNIFICANTLY CHANGE THE INTRACRANIAL DISEASE STAGING

    PubMed Central

    Scoccianti, S.; Greto, D.; Bordi, L.; Bono, P.; Pecchioli, G.; Casati, M.; Vanzi, E.; Compagnucci, A.; Gadda, D.; Livi, L.

    2014-01-01

    INTRODUCTION: Accurate assessment of the exact number of brain metastases is of utmost importance in the decision-making process for the appropriate treatment. The diagnostic efficacy in the detection of additional brain metastases of a double dose contrast three-dimensional, T1-Weighted Gradient-Echo Imaging was evaluated. METHODS: Before undergoing radiosurgical treatment, patients underwent a brain magnetic resonance imaging (MRI) scan to be used during the treatment planning in order to contour the targets and to locate the brain lesions as they relate to the stereotactic frame. All the patients underwent a post-contrast study with T1-weighted, 3D Magnetization-Prepared Rapid Acquisition Gradient Echo (MP RAGE) sequence. We used a double dose of gadobenate dimeglumine and slice thickness of 0.9 mm. RESULTS: Starting from October 2012 to February 2014, we treated with Gamma Knife radiosurgery (GKRS) 62 patients with brain metastases. On the diagnostic MRI, all the patients had a number of lesions ≤4. Median time interval between diagnostic MRI scan and the day of GKRS was 11 days (range 5-20) A total of 54 additional lesions were detected on MR imaging performed in the same day of the GKRS in twenty-two patients out of 62 (35.5%). A median number of 2 additional lesions were detected (range 1-8). Among these 22 patients only 14 patients had a number of lesions ≤4 on the day of treatment. Patients with a total number of lesions ≤10 were treated with GKRS. Two patients with a total number of lesions > 10 were treated with whole brain radiotherapy (WBRT). CONCLUSIONS: A double-contrast study with T1-weighted, volumetric MPRAGE sequence may offer better staging for patients with brain metastases. In our opinion, it should be recommended in all the patients with newly diagnosed brain metastases because the detection of the real number of lesions is crucial for an adequate treatment and it also may lead to choose different therapeutic strategies.

  16. Whole-Brain Radiotherapy With Simultaneous Integrated Boost to Multiple Brain Metastases Using Volumetric Modulated Arc Therapy

    SciTech Connect

    Lagerwaard, Frank J. Hoorn, Elles A.P. van der; Verbakel, Wilko; Haasbeek, Cornelis J.A.; Slotman, Ben J.; Senan, Suresh

    2009-09-01

    Purpose: Volumetric modulated arc therapy (RapidArc [RA]; Varian Medical Systems, Palo Alto, CA) allows for the generation of intensity-modulated dose distributions by use of a single gantry rotation. We used RA to plan and deliver whole-brain radiotherapy (WBRT) with a simultaneous integrated boost in patients with multiple brain metastases. Methods and Materials: Composite RA plans were generated for 8 patients, consisting of WBRT (20 Gy in 5 fractions) with an integrated boost, also 20 Gy in 5 fractions, to Brain metastases, and clinically delivered in 3 patients. Summated gross tumor volumes were 1.0 to 37.5 cm{sup 3}. RA plans were measured in a solid water phantom by use of Gafchromic films (International Specialty Products, Wayne, NJ). Results: Composite RA plans could be generated within 1 hour. Two arcs were needed to deliver the mean of 1,600 monitor units with a mean 'beam-on' time of 180 seconds. RA plans showed excellent coverage of planning target volume for WBRT and planning target volume for the boost, with mean volumes receiving at least 95% of the prescribed dose of 100% and 99.8%, respectively. The mean conformity index was 1.36. Composite plans showed much steeper dose gradients outside Brain metastases than plans with a conventional summation of WBRT and radiosurgery. Comparison of calculated and measured doses showed a mean gamma for double-arc plans of 0.30, and the area with a gamma larger than 1 was 2%. In-room times for clinical RA sessions were approximately 20 minutes for each patient. Conclusions: RA treatment planning and delivery of integrated plans of WBRT and boosts to multiple brain metastases is a rapid and accurate technique that has a higher conformity index than conventional summation of WBRT and radiosurgery boost.

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

    SciTech Connect

    Shultz, David B.; Modlin, Leslie A.; Jayachandran, Priya; Von Eyben, Rie; Gibbs, Iris C.; Choi, Clara Y.H.; Chang, Steven D.; Harsh, Griffith R.; Li, Gordon; Adler, John R.; Hancock, Steven L.; Soltys, Scott G.

    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. Salvage Radiosurgery for Brain Metastases: Prognostic Factors to Consider in Patient Selection

    SciTech Connect

    Kurtz, Goldie; Zadeh, Gelareh; Gingras-Hill, Geneviève; Millar, Barbara-Ann; Laperriere, Normand J.; Bernstein, Mark; Jiang, Haiyan; Ménard, Cynthia; Chung, Caroline

    2014-01-01

    Purpose: Stereotactic radiosurgery (SRS) is offered to patients for recurrent brain metastases after prior brain radiation therapy (RT), but few studies have evaluated the efficacy of salvage SRS or factors to consider in selecting patients for this treatment. This study reports overall survival (OS), intracranial progression-free survival (PFS), and local control (LC) after salvage SRS, and factors associated with outcomes. Methods and Materials: This is a retrospective review of patients treated from 2009 to 2011 with salvage SRS after prior brain RT for brain metastases. Survival from salvage SRS and from initial brain metastases diagnosis (IBMD) was calculated. Univariate and multivariable (MVA) analyses included age, performance status, recursive partitioning analysis (RPA) class, extracranial disease control, and time from initial RT to salvage SRS. Results: There were 106 patients included in the analysis with a median age of 56.9 years (range 32.5-82 years). A median of 2 metastases were treated per patient (range, 1-12) with a median dose of 21 Gy (range, 12-24) prescribed to the 50% isodose. With a median follow-up of 10.5 months (range, 0.1-68.2), LC was 82.8%, 60.1%, and 46.8% at 6 months, 1 year, and 3 years, respectively. Median PFS was 6.2 months (95% confidence interval [CI] = 4.9-7.6). Median OS was 11.7 months (95% CI = 8.1-13) from salvage SRS, and 22.1 months from IBMD (95% CI = 18.4-26.8). On MVA, age (P=.01; hazard ratio [HR] = 1.04; 95% CI = 1.01-1.07), extracranial disease control (P=.004; HR = 0.46; 95% CI = 0.27-0.78), and interval from initial RT to salvage SRS of at least 265 days (P=.001; HR = 2.46; 95% CI = 1.47-4.09) were predictive of OS. Conclusions: This study demonstrates that patients can have durable local control and survival after salvage SRS for recurrent brain metastases. In particular, younger patients with controlled extracranial disease and a durable response to initial brain RT are likely to benefit from salvage SRS.

  19. Targeting SRC in glioblastoma tumors and brain metastases: rationale and preclinical studies

    PubMed Central

    Ahluwalia, Manmeet; de Groot, John; Liu, Wei (Michael)

    2011-01-01

    Glioblastoma (GBM) is an extremely aggressive, infiltrative tumor with a poor prognosis. The regulatory approval of bevacizumab for recurrent GBM has confirmed that molecularly targeted agents have potential for GBM treatment. Preclinical data showing that SRC and SRC-family kinases (SFKs) mediate intracellular signaling pathways controlling key biologic/oncogenic processes provide a strong rationale for investigating SRC/SFK inhibitors, eg, dasatinib, in GBM and clinical studies are underway. The activity of these agents against solid tumors suggests that they may also be useful in treating brain metastases. This article reviews the potential for using SRC/SFK inhibitors to treat GBM and brain metastases. Word count =99/100 PMID:20947248

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

    SciTech Connect

    Ohguri, Takayuki . E-mail: ogurieye@med.uoeh-u.ac.jp; 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.

  1. Recursive partitioning analysis (RPA) of prognostic factors in three radiation therapy oncology group (RTOG) brain metastases trials

    SciTech Connect

    Scott, C.; Gaspar, L.; Rotman, M.

    1995-12-31

    Promising results from new approaches such as radiosurgery or stereotactic radiosurgery of brain metastases have recently been reported. Are these results due to the therapy alone or can the results be attributed in part to patient selection? An analysis of tumor/patient characteristics and treatment variables in previous RTOG brain metastases studies was considered necessary to fully evaluate the benefit of these new interventions.

  2. Erlotinib plus concurrent whole-brain radiation therapy for non-small cell lung cancers patients with multiple brain metastases

    PubMed Central

    Ulahannan, Danny

    2016-01-01

    Sequencing of the epidermal growth factor receptor (EGFR) gene to identify mutations in lung adenocarcinomas is routine in clinical practice. The use of tyrosine kinase inhibitors (TKIs) has transformed the management of patients with brain metastases harboring EGFR mutations, with improved response rates (RR) and survival. We evaluate the role of concurrent TKI therapy and radiotherapy in this group of patients, considering this data in the context of emerging concepts in this advancing field. PMID:27186518

  3. Intracranial hemorrhage in patients with brain metastases treated with therapeutic enoxaparin: a matched cohort study.

    PubMed

    Donato, Jessica; Campigotto, Federico; Uhlmann, Erik J; Coletti, Erika; Neuberg, Donna; Weber, Griffin M; Zwicker, Jeffrey I

    2015-07-23

    Venous thromboembolism occurs frequently in patients with cancer who have brain metastases, but there is limited evidence supporting the safety of therapeutic anticoagulation. To assess the risk for intracranial hemorrhage associated with the administration of therapeutic doses of low-molecular-weight heparin, we performed a matched, retrospective cohort study of 293 patients with cancer with brain metastases (104 with therapeutic enoxaparin and 189 controls). A blinded review of radiographic imaging was performed, and intracranial hemorrhages were categorized as trace, measurable, and significant. There were no differences observed in the cumulative incidence of intracranial hemorrhage at 1 year in the enoxaparin and control cohorts for measurable (19% vs 21%; Gray test, P = .97; hazard ratio, 1.02; 90% confidence interval [CI], 0.66-1.59), significant (21% vs 22%; P = .87), and total (44% vs 37%; P = .13) intracranial hemorrhages. The risk for intracranial hemorrhage was fourfold higher (adjusted hazard ratio, 3.98; 90% CI, 2.41-6.57; P < .001) in patients with melanoma or renal cell carcinoma (N = 60) than lung cancer (N = 153), but the risk was not influenced by the administration of enoxaparin. Overall survival was similar for the enoxaparin and control cohorts (8.4 vs 9.7 months; Log-rank, P = .65). We conclude that intracranial hemorrhage is frequently observed in patients with brain metastases, but that therapeutic anticoagulation does not increase the risk for intracranial hemorrhage. PMID:25987658

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

    SciTech Connect

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

    2007-09-01

    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.

  5. [Whole Brain Irradiation and Hypo-fractionation Radiotherapy for the Metastases in Non-small Cell Lung Cancer].

    PubMed

    Gu, Xingting; Zhao, Yaqin; Xu, Feng

    2016-04-20

    Up to 40% non-small cell lung cancer patients developed brain metastasis during progression. Multiple brain metastases are common in non-small cell lung cancer. The prognosis of brain metastasis is poor with median survival of less than 1 year. Radio therapy for brain metastases has gradually developed from whole brain radiotherapy (WBRT) to various radiation strategies. WBRT, surgery+WBRT, stereotactic radiotherapy+WBRT or WBRT with simultaneous integrated boost (SIB), etc. have better overall survival than those untreated patients. The damage of the cognitive function from WBRT has been realized recently, however, options of radiation strategies for long expected survival patients remain controversial. This paper will discuss different WBRT strategies and treatment side effects of non-small cell lung cancer with brain metastases. PMID:27118651

  6. Structural and functional effects of metastases in rat brain determined by multimodal MRI.

    PubMed

    Serres, Sébastien; Martin, Christopher J; Sarmiento Soto, Manuel; Bristow, Claire; O'Brien, Emma R; Connell, John J; Khrapitchev, Alexandre A; Sibson, Nicola R

    2014-02-15

    Metastasis to the brain results in significant impairment of brain function and poor patient survival. Currently, magnetic resonance imaging (MRI) is under-utilised in monitoring brain metastases and their effects on brain function. Here, we sought to establish a model of focal brain metastasis in the rat that enables serial multimodal structural and functional MRI studies, and to assess the sensitivity of these approaches to metastatic growth. Female Berlin-Druckrey-IX rats were injected intracerebrally with metastatic ENU1564 cells in the ventroposterior medial nucleus (VPM) of the thalamus, a relay node of the whisker-to-barrel cortex pathway. Animals underwent multimodal structural and vascular MRI, as well as functional MRI of the cortical blood oxygenation level dependent (BOLD) responses to whisker pad stimulation. T2 , diffusion, magnetisation transfer and perfusion weighted MRI enabled differentiation between a central area of more advanced metastatic growth and penumbral regions of co-optive perivascular micrometastatic growth, with magnetisation transfer MRI being the most sensitive to micrometastatic growth. Areas of cortical BOLD activation in response to whisker pad stimulation were significantly reduced in the hemisphere containing metastases in the VPM. The reduction in BOLD response correlated with metastatic burden in the thalamus, and was sensitive to the presence of smaller metastases than currently detectable clinically. Our findings suggest that multimodal MRI provides greater sensitivity to tumour heterogeneity and micrometastatic growth than single modality contrast-enhanced MRI. Understanding the relationships between these MRI parameters and the underlying pathology may greatly enhance the utility of MRI in diagnosis, staging and monitoring of brain metastasis. PMID:23913394

  7. Preliminary Results of Whole Brain Radiotherapy With Concurrent Trastuzumab for Treatment of Brain Metastases in Breast Cancer Patients

    SciTech Connect

    Chargari, Cyrus; Idrissi, Hind Riahi; Pierga, Jean-Yves; Bollet, Marc A.; Dieras, Veronique; Campana, Francois; Cottu, Paul; Fourquet, Alain; Kirova, Youlia M.

    2011-11-01

    Purpose: To assess the use of trastuzumab concurrently with whole brain radiotherapy (WBRT) for patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer. Methods and Materials: Between April 2001 and April 2007, 31 patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer were referred for WBRT with concurrent trastuzumab. At brain progression, the median age was 55 years (range, 38-73), and all patients had a performance status of 0-2. The patients received trastuzumab 2 mg/kg weekly (n = 17) or 6 mg/kg repeated every 21 days (n = 14). In 26 patients, concurrent WBRT delivered 30 Gy in 10 daily fractions. In 6 patients, other fractionations were chosen because of either poor performance status or patient convenience. Results: After WBRT, radiologic responses were observed in 23 patients (74.2%), including 6 (19.4%) with a complete radiologic response and 17 (54.8%) with a partial radiologic response. Clinical responses were observed in 27 patients (87.1%). The median survival time from the start of WBRT was 18 months (range, 2-65). The median interval to brain progression was 10.5 months (range, 2-27). No Grade 2 or greater acute toxicity was observed. Conclusion: The low toxicity of trastuzumab concurrently with WBRT should probably not justify delays. Although promising, these preliminary data warrant additional validation of trastuzumab as a potential radiosensitizer for WBRT in brain metastases from breast cancer in the setting of a clinical trial.

  8. Stereotactic Radiotherapy for Cervical Spinal Intramedullary Metastasis and Multiple Brain Metastases: A Case Report.

    PubMed

    Mori, Yoshimasa; Kawamura, Toshiki; Ohshima, Yukihiko; Takeuchi, Arisa; Mori, Toshie; Ishiguchi, Tuneo

    2016-01-01

    A case of cervical (C) spinal intramedullary metastasis and multiple small brain metastases from papillary thyroid carcinoma was presented. Spinal metastasis caused posterior neck and left shoulder pain, dysesthesia in both legs, and motor weakness in both legs and left arm, though the brain metastases were asymptomatic. Both the spinal and brain metastases were successfully treated by frameless stereotactic radiotherapy (SRT)/stereotactic radiosurgery (SRS). The patient's symptoms were almost entirely relieved within two months. A 76-year-old woman was diagnosed as having a thyroid tumor and lung metastasis by roentgenography and computed tomography. Biopsy of the thyroid tumor extending into the mediastinum revealed papillary thyroid carcinoma. She underwent surgical resection of thyroid with dissection of the mediastinum lymph node area. Internal oral radioisotope therapy was not effective for the multiple small lung metastases. She did well for 15 months, but later developed posterior neck and left shoulder pain and dysesthesia in the right leg and then dysesthesia and motor weakness in both legs. Then she experienced weakness in the left upper extremity. Magnetic resonance imaging (MRI) disclosed a small cervical spinal intramedullary mass lesion at the level of C6 and C7 on the left side as well as nine small brain lesions. The cervical spinal intramedullary metastatic tumor was treated by volumetric modulated arc radiotherapy (VMAT) SRT and the nine small brain metastatic tumors were treated by dynamic conformal arc (DCA) SRS uneventfully. A total dose of 39 Gy (100% dose) was delivered in 13 fractions for the spinal lesion (prescription, D95=95% dose; maximum dose=46.3 Gy). Single fraction SRS of 22 Gy (prescription, D95=100% dose) was performed for each of the nine small brain tumors. The spinal tumor was decreased in size on follow-up MRI two months after SRT. Three of the nine brain lesions had disappeared and six were decreased in size on

  9. Stereotactic Radiotherapy for Cervical Spinal Intramedullary Metastasis and Multiple Brain Metastases: A Case Report

    PubMed Central

    Kawamura, Toshiki; Ohshima, Yukihiko; Takeuchi, Arisa; Mori, Toshie; Ishiguchi, Tuneo

    2016-01-01

    A case of cervical (C) spinal intramedullary metastasis and multiple small brain metastases from papillary thyroid carcinoma was presented. Spinal metastasis caused posterior neck and left shoulder pain, dysesthesia in both legs, and motor weakness in both legs and left arm, though the brain metastases were asymptomatic. Both the spinal and brain metastases were successfully treated by frameless stereotactic radiotherapy (SRT)/stereotactic radiosurgery (SRS). The patient's symptoms were almost entirely relieved within two months. A 76-year-old woman was diagnosed as having a thyroid tumor and lung metastasis by roentgenography and computed tomography. Biopsy of the thyroid tumor extending into the mediastinum revealed papillary thyroid carcinoma. She underwent surgical resection of thyroid with dissection of the mediastinum lymph node area. Internal oral radioisotope therapy was not effective for the multiple small lung metastases. She did well for 15 months, but later developed posterior neck and left shoulder pain and dysesthesia in the right leg and then dysesthesia and motor weakness in both legs. Then she experienced weakness in the left upper extremity. Magnetic resonance imaging (MRI) disclosed a small cervical spinal intramedullary mass lesion at the level of C6 and C7 on the left side as well as nine small brain lesions. The cervical spinal intramedullary metastatic tumor was treated by volumetric modulated arc radiotherapy (VMAT) SRT and the nine small brain metastatic tumors were treated by dynamic conformal arc (DCA) SRS uneventfully. A total dose of 39 Gy (100% dose) was delivered in 13 fractions for the spinal lesion (prescription, D95=95% dose; maximum dose=46.3 Gy). Single fraction SRS of 22 Gy (prescription, D95=100% dose) was performed for each of the nine small brain tumors. The spinal tumor was decreased in size on follow-up MRI two months after SRT. Three of the nine brain lesions had disappeared and six were decreased in size on

  10. Characterization of passive permeability at the blood-tumor barrier in five preclinical models of brain metastases of breast cancer.

    PubMed

    Adkins, Chris E; Mohammad, Afroz S; Terrell-Hall, Tori B; Dolan, Emma L; Shah, Neal; Sechrest, Emily; Griffith, Jessica; Lockman, Paul R

    2016-04-01

    The blood-brain barrier (BBB) is compromised in brain metastases, allowing for enhanced drug permeation into brain. The extent and heterogeneity of BBB permeability in metastatic lesions is important when considering the administration of chemotherapeutics. Since permeability characteristics have been described in limited experimental models of brain metastases, we sought to define these changes in five brain-tropic breast cancer cell lines: MDA-MB-231BR (triple negative), MDA-MB-231BR-HER2, JIMT-1-BR3, 4T1-BR5 (murine), and SUM190 (inflammatory HER2 expressing). Permeability was assessed using quantitative autoradiography and fluorescence microscopy by co-administration of the tracers (14)C-aminoisobutyric acid (AIB) and Texas red conjugated dextran prior to euthanasia. Each experimental brain metastases model produced variably increased permeability to both tracers; additionally, the magnitude of heterogeneity was different among each model with the highest ranges observed in the SUM190 (up to 45-fold increase in AIB) and MDA-MB-231BR-HER2 (up to 33-fold in AIB) models while the lowest range was observed in the JIMT-1-BR3 (up to 5.5-fold in AIB) model. There was no strong correlation observed between lesion size and permeability in any of these preclinical models of brain metastases. Interestingly, the experimental models resulting in smaller mean metastases size resulted in shorter median survival while models producing larger lesions had longer median survival. These findings strengthen the evidence of heterogeneity in brain metastases of breast cancer by utilizing five unique experimental models and simultaneously emphasize the challenges of chemotherapeutic approaches to treat brain metastases. PMID:26944053

  11. Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report.

    PubMed

    Morinaga, Nobuhiro; Tanaka, Naritaka; Shitara, Yoshinori; Ishizaki, Masatoshi; Yoshida, Takatomo; Kouga, Hideaki; Wakabayashi, Kazuki; Fukuchi, Minoru; Tsunoda, Yoshiyuki; Kuwano, Hiroyuki

    2016-01-01

    Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. Despite local radiotherapy followed by chemotherapy, the left ovarian lesion grew, so resection of the uterus and bilateral ovaries was performed. Adjuvant chemotherapy with tegafur-uracil (UFT)/calcium folinate (leucovorin, LV) was initiated. Seven months after resection of the ovarian lesion, brain metastases appeared in the bilateral frontal lobes and were treated with stereotactic Gamma Knife radiosurgery. Cervical and mediastinal lymph node metastases were also diagnosed, and irradiation of these lesions was performed. After radiotherapy, 10 courses of oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX) were administered. During FOLFOX administration, recurrent left frontal lobe brain metastasis was diagnosed and treated with stereotactic Gamma Knife radiosurgery. In this case, the brain metastases were well treated with stereotactic Gamma Knife radiosurgery, and the systemic disease arising from sigmoid colon cancer has been kept under control with chemotherapies, surgical resection, and radiotherapy. PMID:27403125

  12. Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report

    PubMed Central

    Morinaga, Nobuhiro; Tanaka, Naritaka; Shitara, Yoshinori; Ishizaki, Masatoshi; Yoshida, Takatomo; Kouga, Hideaki; Wakabayashi, Kazuki; Fukuchi, Minoru; Tsunoda, Yoshiyuki; Kuwano, Hiroyuki

    2016-01-01

    Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. Despite local radiotherapy followed by chemotherapy, the left ovarian lesion grew, so resection of the uterus and bilateral ovaries was performed. Adjuvant chemotherapy with tegafur-uracil (UFT)/calcium folinate (leucovorin, LV) was initiated. Seven months after resection of the ovarian lesion, brain metastases appeared in the bilateral frontal lobes and were treated with stereotactic Gamma Knife radiosurgery. Cervical and mediastinal lymph node metastases were also diagnosed, and irradiation of these lesions was performed. After radiotherapy, 10 courses of oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX) were administered. During FOLFOX administration, recurrent left frontal lobe brain metastasis was diagnosed and treated with stereotactic Gamma Knife radiosurgery. In this case, the brain metastases were well treated with stereotactic Gamma Knife radiosurgery, and the systemic disease arising from sigmoid colon cancer has been kept under control with chemotherapies, surgical resection, and radiotherapy. PMID:27403125

  13. Patterns of Practice of Palliative Radiotherapy in Africa, Part 1: Bone and Brain Metastases

    SciTech Connect

    Sharma, Vinay Gaye, Papa Macoumba M.Med.; Wahab, Sherif Abdel; Ndlovu, Ntokozo; Ngoma, Twalib; Vanderpuye, Verna; Sowunmi, Anthonia; Kigula-Mugambe, Joseph; Jeremic, Branislav

    2008-03-15

    Purpose: To provide data on the pattern of practice of palliative radiotherapy (RT) on the African continent. Methods and Materials: A questionnaire was distributed to participants in a regional training course of the International Atomic Energy Agency in palliative cancer care and sent by e-mail to other institutions in Africa. Requested information included both infrastructure and human resources available and the pattern of RT practice for metastatic and locally advanced cancers. Results: Of 35 centers contacted, 24 (68%) completed the questionnaire. Although RT is used by most centers for most metastatic cancers, liver and lung metastases are treated with chemotherapy. Of 23 centers, 14 (61%) had a single RT regimen as an institutional policy for treating painful bone metastases, but only 5 centers (23%) of 23 used 8 Gy in 1 fraction. Brain metastases were being treated by RT to the whole brain to 30 Gy in 10 fractions, either exclusively (n = 13, 56%) or in addition to the use of 20 Gy in 5 fractions (n = 3, 14%). Conclusion: Radiotherapy is a major component of treatment of cancer patients in African countries. There is consensus among few centers for treatment schedules for almost all sites regarding time and dose-fractionation characteristics of RT regimens used and/or indications for the use of RT in this setting.

  14. Impact of Triple-Negative Phenotype on Prognosis of Patients With Breast Cancer Brain Metastases

    SciTech Connect

    Xu Zhiyuan; Schlesinger, David; Toulmin, Sushila; Rich, Tyvin; Sheehan, Jason

    2012-11-01

    Purpose: To elucidate survival times and identify potential prognostic factors in patients with triple-negative (TN) phenotype who harbored brain metastases arising from breast cancer and who underwent stereotactic radiosurgery (SRS). Methods and Materials: A total of 103 breast cancer patients with brain metastases were treated with SRS and then studied retrospectively. Twenty-four patients (23.3%) were TN. Survival times were estimated using the Kaplan-Meier method, with a log-rank test computing the survival time difference between groups. Univariate and multivariate analyses to predict potential prognostic factors were performed using a Cox proportional hazard regression model. Results: The presence of TN phenotype was associated with worse survival times, including overall survival after the diagnosis of primary breast cancer (43 months vs. 82 months), neurologic survival after the diagnosis of intracranial metastases, and radiosurgical survival after SRS, with median survival times being 13 months vs. 25 months and 6 months vs. 16 months, respectively (p < 0.002 in all three comparisons). On multivariate analysis, radiosurgical survival benefit was associated with non-TN status and lower recursive partitioning analysis class at the initial SRS. Conclusion: The TN phenotype represents a significant adverse prognostic factor with respect to overall survival, neurologic survival, and radiosurgical survival in breast cancer patients with intracranial metastasis. Recursive partitioning analysis class also served as an important and independent prognostic factor.

  15. Prophylactic irradiation of the lungs to prevent development of pulmonary metastases in patients with osteosarcoma of the limbs

    SciTech Connect

    Breur, K.; Schweisguth, O.; Cohen, P.; Voute, P.A.

    1981-04-01

    A controlled clinical trial conducted by the European Organization for Research on Treatment of Cancer Radiotherapy Cooperative Group has shown that prophylactic lung irradiation is effective in preventing lung metastases in patients under 17 years of age. Recently, a new three-armed trial has started in which prophylactic chemotherapy and lung irradiation and chemotherapy combined with radiotherapy to the lungs will be compared for their ability to prevent the development of lung metastases.

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

    PubMed

    Chang, Alex Y; Ying, Xu Xiao

    2015-01-01

    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. PMID:26052228

  17. Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases.

    PubMed

    Kohutek, Zachary A; Yamada, Yoshiya; Chan, Timothy A; Brennan, Cameron W; Tabar, Viviane; Gutin, Philip H; Yang, T Jonathan; Rosenblum, Marc K; Ballangrud, Åse; Young, Robert J; Zhang, Zhigang; Beal, Kathryn

    2015-10-01

    Radionecrosis is a well-characterized effect of stereotactic radiosurgery (SRS) and is occasionally associated with serious neurologic sequelae. Here, we investigated the incidence of and clinical variables associated with the development of radionecrosis and related radiographic changes after SRS for brain metastases in a cohort of patients with long-term follow up. 271 brain metastases treated with single-fraction linear accelerator-based SRS were analyzed. Radionecrosis was diagnosed either pathologically or radiographically. Univariate and multivariate Cox regression was performed to determine the association between radionecrosis and clinical factors available prior to treatment planning. After median follow up of 17.2 months, radionecrosis was observed in 70 (25.8%) lesions, including 47 (17.3%) symptomatic cases. 22 of 70 cases (31.4%) were diagnosed pathologically and 48 (68.6%) were diagnosed radiographically. The actuarial incidence of radionecrosis was 5.2% at 6 months, 17.2% at 12 months and 34.0% at 24 months. On univariate analysis, radionecrosis was associated with maximum tumor diameter (HR 3.55, p < 0.001), prior whole brain radiotherapy (HR 2.21, p = 0.004), prescription dose (HR 0.56, p = 0.02) and histology other than non-small cell lung, breast or melanoma (HR 1.85, p = 0.04). On multivariate analysis, only maximum tumor diameter (HR 3.10, p < 0.001) was associated with radionecrosis risk. This data demonstrates that with close imaging follow-up, radionecrosis after single-fraction SRS for brain metastases is not uncommon. Maximum tumor diameter on pre-treatment MR imaging can provide a reliable estimate of radionecrosis risk prior to treatment planning, with the greatest risk among tumors measuring >1 cm. PMID:26307446

  18. Delayed Effects of Whole Brain Radiotherapy in Germ Cell Tumor Patients With Central Nervous System Metastases

    SciTech Connect

    Doyle, Danielle M. Einhorn, Lawrence H.

    2008-04-01

    Purpose: Central nervous system (CNS) metastases are uncommon in patients with germ cell tumors, with an incidence of 2-3%. CNS metastases have been managed with whole brain radiotherapy (WBRT) and concomitant cisplatin-based combination chemotherapy. Our previous study did not observe serious CNS toxicity (Int J Radiat Oncol Biol Phys 1991;22:17-22). We now report on 5 patients who developed delayed significant CNS toxicity. Patients and Methods: We observed 5 patients with delayed CNS toxicity. The initial diagnosis was between 1981 and 2003. All patients had poor-risk disease according to the International Germ Cell Consensus Collaborative Group criteria. Of the 5 patients, 3 had CNS metastases at diagnosis and 2 developed relapses with CNS metastases. These 5 patients underwent WBRT to 4,000-5,000 cGy in 18-28 fractions concurrently with cisplatin-based chemotherapy. Results: All 5 patients developed delayed symptoms consistent with progressive multifocal leukoencephalopathy. The symptoms included seizures, hemiparesis, cranial neuropathy, headaches, blindness, dementia, and ataxia. The median time from WBRT to CNS symptoms was 72 months (range, 9-228). Head imaging revealed multiple abnormalities consistent with gliosis and diffuse cerebral atrophy. Of the 5 patients, 3 had progressive and 2 stable symptoms. Treatment with surgery and/or steroids had modest benefit. The progressive multifocal leukoencephalopathy resulted in significant debility in all 5 patients, resulting in death (3 patients), loss of work, steroid-induced morbidity, and recurrent hospitalizations. Conclusion: Whole brain radiotherapy is not innocuous in young patients with germ cell tumors and can cause late CNS toxicity.

  19. Metastasis-inducing proteins are widely expressed in human brain metastases and associated with intracranial progression and radiation response

    PubMed Central

    Zakaria, Rasheed; Platt-Higgins, Angela; Rathi, Nitika; Crooks, Daniel; Brodbelt, Andrew; Chavredakis, Emmanuel; Lawson, David; Jenkinson, Michael D; Rudland, Philip S

    2016-01-01

    Background: Understanding the factors that drive recurrence and radiosensitivity in brain metastases would improve prediction of outcomes, treatment planning and development of therapeutics. We investigated the expression of known metastasis-inducing proteins in human brain metastases. Methods: Immunohistochemistry on metastases removed at neurosurgery from 138 patients to determine the degree and pattern of expression of the proteins S100A4, S100P, AGR2, osteopontin (OPN) and the DNA repair marker FANCD2. Validation of significant findings in a separate prospective series with the investigation of intra-tumoral heterogeneity using image-guided sampling. Assessment of S100A4 expression in brain metastatic and non-metastatic primary breast carcinomas. Results: There was widespread staining for OPN, S100A4, S100P and AGR2 in human brain metastases. Positive staining for S100A4 was independently associated with a shorter time to intracranial progression after resection in multivariate analysis (hazard ratio for negative over positive staining=0.17, 95% CI: 0.04–0.74, P=0.018). S100A4 was expressed at the leading edge of brain metastases in image guided sampling and overexpressed in brain metastatic vs non-brain metastatic primary breast carcinomas. Staining for OPN was associated with a significant increase in survival time after post-operative whole-brain radiotherapy in retrospective (OPN negative 3.43 months, 95% CI: 1.36–5.51 vs OPN positive, 11.20 months 95% CI: 7.68–14.72, Log rank test, P<0.001) and validation populations. Conclusions: Proteins known to be involved in cellular adhesion and migration in vitro, and metastasis in vivo are significantly expressed in human brain metastases and may be useful biomarkers of intracranial progression and radiosensitivity. PMID:27100728

  20. Stereotactic Radiosurgery for Patients With Brain Metastases From Small Cell Lung Cancer

    SciTech Connect

    Wegner, Rodney E.; Olson, Adam C.; Kondziolka, Douglas; Niranjan, Ajay; Lundsford, L. Dade; Flickinger, John C.

    2011-11-01

    Background: Patients with small-cell lung cancer have a high likelihood of developing brain metastases. Many of these patients will have prophylactic cranial irradiation (PCI) or eventually undergo whole brain radiation therapy (WBRT). Despite these treatments, a large number of these patients will have progression of their intracranial disease and require additional local therapy. Stereotactic radiosurgery (SRS) is an important treatment option for such patients. Methods: We retrospectively reviewed the charts of 44 patients with brain metastases from small-cell lung cancer treated with gamma knife SRS. Multivariate analysis was used to determine significant prognostic factors influencing survival. Results: The median follow-up from SRS in this patient population was 9 months (1-49 months). The median overall survival (OS) was 9 months after SRS. Karnofsky performance status (KPS) and combined treatment involving WBRT and SRS within 4 weeks were the two factors identified as being significant predictors of increased OS (p = 0.033 and 0.040, respectively). When comparing all patients, patients treated with a combined approach had a median OS of 14 months compared to 6 months if SRS was delivered alone. We also compared the OS times from the first definitive radiation: WBRT, WBRT and SRS if combined therapy was used, and SRS if the patient never received WBRT. The median survival for those groups was 12, 14, and 13 months, respectively, p = 0.19. Seventy percent of patients had follow-up magnetic resonance imaging available for review. Actuarial local control at 6 months and 12 months was 90% and 86%, respectively. Only 1 patient (2.2%) had symptomatic intracranial swelling related to treatment, which responded to a short course of steroids. New brain metastases outside of the treated area developed in 61% of patients at a median time of 7 months; 81% of these patients had received previous WBRT. Conclusions: Stereotactic radiosurgery for small-cell lung carcinoma

  1. Spine Stereotactic Body Radiotherapy Outcomes in Patients with Concurrent Brain Metastases

    PubMed Central

    Park, Henry S; Laurans, Maxwell S; Chiang, Veronica S; Yu, James B; Husain, Zain A

    2016-01-01

    Objectives: Stereotactic body radiotherapy (SBRT) is an emerging technique for maximizing tumor and pain control in selected patients with spinal metastases. Outcomes for those with concurrent brain metastases (CBM) have not been well-described previously. The goal of this study was to compare outcomes for patients with or without CBM treated with spine SBRT. Methods: Records of all patients treated with SBRT for spine metastases at our institution from January 2008 to January 2014 were reviewed. Chi-square analyses and the Mann-Whitney test were used to assess the association of CBM (defined as brain metastasis present prior to or at the time of spinal SBRT) with potential covariates. The log-rank test and Cox proportional hazards regression were used to evaluate the impact of CBM on overall survival and local control from the time of the first course of spine SBRT. Results: Seventy-eight patients and a total of 86 SBRT lesions were treated. Median patient age was 60 years (range: 38-84 years); 28.2% had radioresistant histologies. A single fraction was used in 91.0% of treatments. One-year local control was 89.4%, and one-year overall survival was 45.8%. A total of 19 patients (24.4%) had CBM. Among these CBM patients, 18 (94.7%) underwent intracranial radiosurgery and nine (47.4%) were diagnosed synchronously with their spine metastases. Local control was not significantly different between patients with or without CBM on univariable (median: 58 months vs. not reached, p = 0.53) or multivariable analyses (HR 0.52, 95% CI 0.06-4.33). Overall survival was also not significantly different between patients with or without CBM on univariable (median: 7 vs. 11 months, log-rank p = 0.12) or multivariable analyses (HR 1.62, 95% CI 0.87-3.03). Conclusions: Patients with CBM do not appear to have a statistically significant detriment in clinical outcomes, suggesting that CBM should not necessarily be considered a contraindication for spine SBRT. Although our

  2. Long-term follow-up for brain metastases treated by percutaneous stereotactic single high-dose irradiation.

    PubMed

    Engenhart, R; Kimmig, B N; Höver, K H; Wowra, B; Romahn, J; Lorenz, W J; van Kaick, G; Wannenmacher, M

    1993-02-15

    Surgery is considered the treatment of choice for solitary brain lesions, and radiation therapy is indicated for metastases only in vital or sensitive regions that cannot be excised without risk of disabling neurologic defects. In these cases, radiosurgery may be an alternative to conventionally fractionated radiation therapy. At the Heidelberg linear accelerator-based radiosurgery facility, 69 patients were treated for 102 inoperable brain metastases. The primary tumor sites included non-small cell lung carcinoma (n = 24), renal cell carcinoma (n = 14), melanoma (skin) (n = 14), colorectal carcinoma (n = 6), carcinoma of unknown primary (n = 4), and others (n = 7). Eleven patients were treated for relapse after surgery or after conventional whole-brain irradiation. The doses at the isocenter varied from 15-50 Gy (mean, 21.5 Gy). Ten patients with multiple metastases received a planned combination of whole-brain irradiation plus a single boost of 15 Gy. The median survival time for the entire group was 6 months, with a 1-year-survival of 28.3%. Factors associated with significant improvement of survival were brain metastases without other metastatic disease and good response to radiation therapy. Five of 22 patients (22.9%) with metastases located only in the brain survived longer than 2 years. An improvement in neurologic function was found in 81% within a period of 3 months. With imaging techniques, complete remission was found in 20%, partial remission in 35%, stable disease in 40%, and relapse in 5%. The authors concluded that radiosurgery is an effective and safe therapy for brain metastases. It can be applied as primary treatment, as boost in combination with whole-brain irradiation, or as treatment for patients with relapse in a previously irradiated field. PMID:8435811

  3. Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial12

    PubMed Central

    Kim, Michelle M.; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A.; Oronsky, Arnold; Knox, Susan J.; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S.; Lao, Christopher D.

    2016-01-01

    BACKGROUND: Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. SIGNIFICANCE: Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. PMID:27084426

  4. Treatment of brain metastases of renal cell cancer with combined hypofractionated stereotactic radiotherapy and whole brain radiotherapy with hippocampal sparing

    PubMed Central

    VRÁNA, DAVID; ŠTUDENTOVÁ, HANA; MATZENAUER, MARCEL; VLACHOVÁ, ZUZANA; CWIERTKA, KAREL; GREMLICA, DAVID; KALITA, ONDŘEJ

    2016-01-01

    Renal cell cancer patients with brain metastatic disease generally have poor prognosis. Treatment options include surgery, radiotherapy, targeted therapy or best supportive care with respect to disease burden, patient preference and performance status. In the present case report the radiotherapy technique combining whole brain radiotherapy with hippocampal sparing (hippocampal avoidance whole brain radiotherapy HA-WBRT) and hypofractionated stereotactic radiotherapy (SRT) of the brain metastases is performed in a patient with metastatic renal cell carcinoma. HA-WBRT was administered to 30 Gy in 10 fractions with sparing of the hippocampal structures and SRT of 21 Gy in 3 fractions to brain metastases which has preceded the HA-WBRT. Two single arc volumetric modulated arc radiotherapy (VMAT) plans were prepared using Monaco planning software. The HA-WBRT treatment plan achieved the following results: D2=33.91 Gy, D98=25.20 Gy, D100=14.18 Gy, D50=31.26 Gy. The homogeneity index was calculated as a deduction of the minimum dose in 2% and 98% of the planning target volume (PTV), divided by the minimum dose in 50% of the PTV. The maximum dose to the hippocampus was 17.50 Gy and mean dose was 11.59 Gy. The following doses to organs at risk (OAR) were achieved: Right opticus Dmax, 31.96 Gy; left opticus Dmax, 30.96 Gy; chiasma D max, 32,76 Gy. The volume of PTV for stereotactic radiotherapy was 3,736 cm3, with coverage D100=20.95 Gy and with only 0.11% of the PTV being irradiated to dose below the prescribed dose. HA-WBRT with SRT represents a feasible technique for radiotherapy of brain metastatic disease, however this technique is considerably demanding on departmental equipment and staff time/experience. PMID:27313693

  5. Alveolar soft part sarcoma associated with lung and brain metastases: A case report

    PubMed Central

    Wang, Mingguang; Li, Jinxing; Huan, Linchun; Meng, Fanguo; Pang, Qi

    2016-01-01

    The present case report aimed to improve the understanding of alveolar soft part sarcoma (ASPS) by investigating the clinical characteristics, diagnosis and therapeutic methods used to treat ASPS associated with lung and brain metastases. The clinical data of a single patient diagnosed with ASPS by postoperative pathology was studied retrospectively, and additional associated reports and previous studies of similar cases were reviewed. Clinical symptoms were markedly alleviated following surgical treatment, followed by a chemotherapy regime. During post-treatment follow-up, no tumor recurrence was observed.

  6. O7.01RESPONSE ASSESSMENT IN NEURO-ONCOLOGY (RANO) CRITERIA FOR BRAIN METASTASES

    PubMed Central

    Wen, P.Y.; Lee, E.Q.; Van Den Bent, M.; Soffieti, R.; Bendszus, M.; Mehta, M.; Baumert, B.; Vogelbaum, M.; Chang, S.M.; Lin, N.U.

    2014-01-01

    Currently, there are no standard criteria for evaluating response to therapy in patients with brain metastases. An international multidisciplinary group, The Response Assessment in Neuro-Oncology (RANO) Metastatic Working Group has proposed a RANO-Brain Metastases (RANO-BM) Criteria is based on a modification of RECIST 1.1 criteria and uses unidimensional measurements. Since the CNS is considered as a separate compartment. CNS response will be scored independent of extracranial response. Measurable disease is defined as a contrast enhancing lesion that can be accurately measured in at least one dimension with a minimum size of 10 mm, visible on two or more axial slices that are preferably at most 5 mm apart with no gap. In addition, although the longest diameter in the plane of measurement is to be recorded, the diameter perpendicular to the longest diameter in the plane of measurement should be at least 5 mm for the lesion to be considered measurable. Best overall CNS response represents a composite of radiographic CNS target and non-target response, corticosteroid use, and clinical status. In non-randomized trials where CNS response is the primary endpoint, confirmation of PR or CR at least 4 weeks later is required. The proposed criteria are: Complete response (CR): Disappearance of all CNS target lesions sustained for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. Partial response (PR): At least a 30% decrease in the sum longest diameter (LD) of CNS target lesions, taking as reference the baseline sum LD, sustained for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. Progressive disease (PD): At least a 20% increase in the sum LD of CNS target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The group is

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

    PubMed Central

    He, Yayi; Sun, Wenwen; Wang, Yan; Ren, Shengxiang; Li, Xuefei; Li, Jiayu; Rivard, Christopher J; Zhou, Caicun; Hirsch, Fred R

    2016-01-01

    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 effects in the pemetrexed-group were vomiting and nausea. Conclusion Erlotinib and pemetrexed may be used as second-/third-line treatment in lung adenocarcinoma patients with asymptomatic brain metastases, and detection of EGFR mutation status is very important in these patients. EGFR mutation–positive lung adenocarcinoma patients with asymptomatic brain metastases showed longer PFS when treated with erlotinib as opposed to pemetrexed. PMID:27143936

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

    SciTech Connect

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

    2012-11-01

    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.

  9. Methodology for fiber-optic Raman mapping and FTIR imaging of metastases in mouse brains.

    PubMed

    Krafft, Christoph; Kirsch, Matthias; Beleites, Claudia; Schackert, Gabriele; Salzer, Reiner

    2007-10-01

    The objectives of this study were to optimize the preparation of pristine brain tissue to obtain reference information, to optimize the conditions for introducing a fiber-optic probe to acquire Raman maps, and to transfer previous results obtained from human brain tumors to an animal model. Brain metastases of malignant melanomas were induced by injecting tumor cells into the carotid artery of mice. The procedure mimicked hematogenous tumor spread in one brain hemisphere while the other hemisphere remained tumor free. Three series of sections were prepared consecutively from whole mouse brains: dried, thin sections for FTIR imaging, hematoxylin and eosin-stained thin sections for histopathological assessment, and pristine, 2-mm thick sections for Raman mapping. FTIR images were recorded using a spectrometer with a multi-channel detector. Raman maps were collected serially using a spectrometer coupled to a fiber-optic probe. The FTIR images and the Raman maps were segmented by cluster analysis. The color-coded cluster memberships coincided well with the morphology of mouse brains in stained tissue sections. More details in less time were resolved in FTIR images with a nominal resolution of 25 microm than in Raman maps collected with a laser focus 60 microm in diameter. The spectral contributions of melanin in tumor cells were resonance enhanced in Raman spectra on excitation at 785 nm which enabled their sensitive detection in Raman maps. Possible reasons why metastatic cells of malignant melanomas were not identified in FTIR images are discussed. PMID:17639353

  10. Acetate is a Bioenergetic Substrate for Human Glioblastoma and Brain Metastases

    PubMed Central

    Mashimo, Tomoyuki; Pichumani, Kumar; Vemireddy, Vamsidhara; Hatanpaa, Kimmo J.; Singh, Dinesh Kumar; Sirasanagandla, Shyam; Nannepaga, Suraj; Piccirillo, Sara G.; Kovacs, Zoltan; Foong, Chan; Huang, Zhiguang; Barnett, Samuel; Mickey, Bruce E.; DeBerardinis, Ralph J.; Tu, Benjamin P.; Maher, Elizabeth A.; Bachoo, Robert M.

    2015-01-01

    Glioblastomas and brain metastases are highly proliferative brain tumors with short survival times. Previously, using 13C-NMR analysis of brain tumors resected from patients during infusion of 13C-glucose, we demonstrated that there is robust oxidation of glucose in the citric acid cycle, yet glucose contributes less than 50% of the carbons to the acetyl-CoA pool. Here we show that primary and metastatic mouse orthotopic brain tumors have the capacity to oxidize [1,2-13C]acetate and can do so simultaneously with [1,6-13C]glucose oxidation. The tumors do not oxidize [U-13C]glutamine. In vivo oxidation of [1,2-13C]acetate was validated in brain tumor patients and was correlated with expression of acetyl-CoA synthetase enzyme 2, ACSS2. Together the data demonstrate a strikingly common metabolic phenotype in diverse brain tumors that includes the ability to oxidize acetate in the citric acid cycle. This adaptation may be important for meeting the high biosynthetic and bioenergetic demands of malignant growth. PMID:25525878

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

    SciTech Connect

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

    2010-04-15

    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 <2.0 cm in diameter. The mean dose to the hippocampus was kept at <6 Gy{sub 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{sub 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.

  12. Treatment of brain metastases of lung cancer in the era of precision medicine.

    PubMed

    Haughton, Michael E; Chan, Michael D; Watabe, Kounosuke; Bonomi, Marcelo; Debinski, Waldemar; Lesser, Glenn J; Ruiz, Jimmy

    2016-01-01

    Common and deadly complications of non-small cell lung cancer (NSCLC) are brain metastases (BM). BM portends a poorer prognosis with limited effective treatment options and current management strategies present several challenges from iatrogenic complications of supportive medications, optimal delivery of drug across the blood-brain barrier, and preservation of neurocognitive function. Long term side effects and survivorship issues have become more evident in the era of targeted therapy where a systemic disease is much better controlled. Targeted therapies and immunotherapy are beginning to provide improvements in responses and survival rates. With further advancements and experience, our knowledge in this era of precision medicine will likely lead to strides in improving the quality of life and overall survival of patients with BM from NSCLC. In this review, we present the most recent updates in treatment of BM in NSCLC in regards to targeted and immunotherapy. PMID:26709658

  13. Prognostic Factors for Survival in Patients Treated With Stereotactic Radiosurgery for Recurrent Brain Metastases After Prior Whole Brain Radiotherapy

    SciTech Connect

    Caballero, Jorge A.; Sneed, Penny K.; Lamborn, Kathleen R.; Ma, Lijun; Denduluri, Sandeep; Nakamura, Jean L.; Barani, Igor J.; McDermott, Michael W.

    2012-05-01

    Purpose: To evaluate prognostic factors for survival after stereotactic radiosurgery (SRS) for new, progressive, or recurrent brain metastases (BM) after prior whole brain radiotherapy (WBRT). Methods and Materials: Patients treated between 1991 and 2007 with Gamma Knife SRS for BM after prior WBRT were retrospectively reviewed. Potential prognostic factors were analyzed overall and by primary site using univariate and stepwise multivariate analyses and recursive partitioning analysis, including age, Karnofsky performance status (KPS), primary tumor control, extracranial metastases, number of BM treated, total SRS target volume, and interval from WBRT to SRS. Results: A total of 310 patients were analyzed, including 90 breast, 113 non-small-cell lung, 31 small-cell lung, 42 melanoma, and 34 miscellaneous patients. The median age was 56, KPS 80, number of BM treated 3, and interval from WBRT to SRS 8.1 months; 76% had controlled primary tumor and 60% had extracranial metastases. The median survival was 8.4 months overall and 12.0 vs. 7.9 months for single vs. multiple BM treated (p = 0.001). There was no relationship between number of BM and survival after excluding single-BM patients. On multivariate analysis, favorable prognostic factors included age <50, smaller total target volume, and longer interval from WBRT to SRS in breast cancer patients; smaller number of BM, KPS >60, and controlled primary in non-small-cell lung cancer patients; and smaller total target volume in melanoma patients. Conclusions: Among patients treated with salvage SRS for BM after prior WBRT, prognostic factors appeared to vary by primary site. Although survival time was significantly longer for patients with a single BM, the median survival time of 7.9 months for patients with multiple BM seems sufficiently long for salvage SRS to appear to be worthwhile, and no evidence was found to support the use of a cutoff for number of BM appropriate for salvage SRS.

  14. Five-year survivors of brain metastases: A single-institution report of 32 patients

    SciTech Connect

    Chao, Samuel T.; Barnett, Gene H.; Liu, Stephanie W.; Reuther, Alwyn M.; Toms, Steven A.; Vogelbaum, Michael A.; Videtic, Gregory; Suh, John H. . E-mail: suhj@ccf.org

    2006-11-01

    Purpose: To report on 32 patients who survived {>=}5 years from brain metastases treated at a single institution. Methods and Materials: The records of 1288 patients diagnosed with brain metastases between 1973 and 1999 were reviewed. Patients were treated with whole-brain radiation therapy (WBRT), surgery, and/or stereotactic radiosurgery (SRS). Thirty-two (2.5%) {>=}5-year survivors were identified. Factors contributing to long-term survival were identified. Results: Median survival was 9.3 years for {>=}5-year survivors. Seven of these patients lived {>=}10 years. Female gender was the only patient characteristic that correlated with better survival (p = 0.0369). When these patients were compared with <5-year survivors, age <65 years (p = 0.0044), control of the primary at diagnosis (p = 0.0052), no systemic disease (p = 0.0012), recursive partitioning analysis (RPA) Class 1 (p = 0.0002 with Class 2; p = 0.0022 with Class 3), and single brain metastasis (p = 0.0018) were associated with long-term survival in the univariate logistic regression model. In the multivariate model, RPA Class 1 compared with Class 2 (OR = 0.39, p = 0.0196), surgery (OR = 0.16, p < 0.0001), and SRS (OR = 0.41, p = 0.0188) were associated with long-term survival. Conclusions: For patients with good prognostic factors such as young age, good RPA characteristics and single metastasis, treatment with surgery or SRS offers the best chance for long-term survival.

  15. Cytogenomic profiling of breast cancer brain metastases reveals potential for repurposing targeted therapeutics

    PubMed Central

    Bollig-Fischer, Aliccia; Michelhaugh, Sharon K.; Wijesinghe, Priyanga; Dyson, Greg; Kruger, Adele; Palanisamy, Nallasivam; Choi, Lydia; Alosh, Baraa; Ali-Fehmi, Rouba; Mittal, Sandeep

    2015-01-01

    Breast cancer brain metastases remain a significant clinical problem. Chemotherapy is ineffective and a lack of treatment options result in poor patient outcomes. Targeted therapeutics have proven to be highly effective in primary breast cancer, but lack of molecular genomic characterization of metastatic brain tumors is hindering the development of new treatment regimens. Here we contribute to fill this void by reporting on gene copy number variation (CNV) in 10 breast cancer metastatic brain tumors, assayed by array comparative genomic hybridization (aCGH). Results were compared to a list of cancer genes verified by others to influence cancer. Cancer gene aberrations were identified in all specimens and pathway-level analysis was applied to aggregate data, which identified stem cell pluripotency pathway enrichment and highlighted recurring, significant amplification of SOX2, PIK3CA, NTRK1, GNAS, CTNNB1, and FGFR1. For a subset of the metastatic brain tumor samples (n=4) we compared patient-matched primary breast cancer specimens. The results of our CGH analysis and validation by alternative methods indicate that oncogenic signals driving growth of metastatic tumors exist in the original cancer. This report contributes support for more rapid development of new treatments of metastatic brain tumors, the use of genomic-based diagnostic tools and repurposed drug treatments. PMID:25970776

  16. Intensity-modulated radiosurgery with rapidarc for multiple brain metastases and comparison with static approach

    SciTech Connect

    Wang Jiazhu; Pawlicki, Todd; Rice, Roger; Mundt, Arno J.; Sandhu, Ajay; Lawson, Joshua; Murphy, Kevin T.

    2012-04-01

    Rotational RapidArc (RA) and static intensity-modulated radiosurgery (IMRS) have been used for brain radiosurgery. This study compares the 2 techniques from beam delivery parameters and dosimetry aspects for multiple brain metastases. Twelve patients with 2-12 brain lesions treated with IMRS were replanned using RA. For each patient, an optimal 2-arc RA plan from several trials was chosen for comparison with IMRS. Homogeneity, conformity, and gradient indexes have been calculated. The mean dose to normal brain and maximal dose to other critical organs were evaluated. It was found that monitor unit (MU) reduction by RA is more pronounced for cases with larger number of brain lesions. The MU-ratio of RA and IMRS is reduced from 104% to 39% when lesions increase from 2 to 12. The dose homogeneities are comparable in both techniques and the conformity and gradient indexes and critical organ doses are higher in RA. Treatment time is greatly reduced by RA in intracranial radiosurgery, because RA uses fewer MUs, fewer beams, and fewer couch angles.

  17. Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

    SciTech Connect

    Hartford, Alan C.; Paravati, Anthony J.; Spire, William J.; Li, Zhongze; Jarvis, Lesley A.; Fadul, Camilo E.; Erkmen, Kadir; Friedman, Jonathan; Gladstone, David J.; Hug, Eugen B.; Roberts, David W.; Simmons, Nathan E.

    2013-03-01

    Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, for time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to

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

    SciTech Connect

    Niwinska, Anna; Tacikowska, Malgorzata; Murawska, Magdalena

    2010-07-15

    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.

  19. Delayed Complications in Patients Surviving at Least 3 Years After Stereotactic Radiosurgery for Brain Metastases

    SciTech Connect

    Yamamoto, Masaaki; Kawabe, Takuya; Higuchi, Yoshinori; Sato, Yasunori; Nariai, Tadashi; Barfod, Bierta E.; Kasuya, Hidetoshi; Urakawa, Yoichi

    2013-01-01

    Purpose: Little is known about delayed complications after stereotactic radiosurgery in long-surviving patients with brain metastases. We studied the actual incidence and predictors of delayed complications. Patients and Methods: This was an institutional review board-approved, retrospective cohort study that used our database. Among our consecutive series of 2000 patients with brain metastases who underwent Gamma Knife radiosurgery (GKRS) from 1991-2008, 167 patients (8.4%, 89 women, 78 men, mean age 62 years [range, 19-88 years]) who survived at least 3 years after GKRS were studied. Results: Among the 167 patients, 17 (10.2%, 18 lesions) experienced delayed complications (mass lesions with or without cyst in 8, cyst alone in 8, edema in 2) occurring 24.0-121.0 months (median, 57.5 months) after GKRS. The actuarial incidences of delayed complications estimated by competing risk analysis were 4.2% and 21.2% at the 60th month and 120th month, respectively, after GKRS. Among various pre-GKRS clinical factors, univariate analysis demonstrated tumor volume-related factors: largest tumor volume (hazard ratio [HR], 1.091; 95% confidence interval [CI], 1.018-1.154; P=.0174) and tumor volume {<=}10 cc vs >10 cc (HR, 4.343; 95% CI, 1.444-12.14; P=.0108) to be the only significant predictors of delayed complications. Univariate analysis revealed no correlations between delayed complications and radiosurgical parameters (ie, radiosurgical doses, conformity and gradient indexes, and brain volumes receiving >5 Gy and >12 Gy). After GKRS, an area of prolonged enhancement at the irradiated lesion was shown to be a possible risk factor for the development of delayed complications (HR, 8.751; 95% CI, 1.785-157.9; P=.0037). Neurosurgical interventions were performed in 13 patients (14 lesions) and mass removal for 6 lesions and Ommaya reservoir placement for the other 8. The results were favorable. Conclusions: Long-term follow-up is crucial for patients with brain metastases

  20. Proactive Management for Gastric, Colorectal and Appendiceal Malignancies: Preventing Peritoneal Metastases with Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

    PubMed

    Sammartino, Paolo; Biacchi, Daniele; Cornali, Tommaso; Cardi, Maurizio; Accarpio, Fabio; Impagnatiello, Alessio; Sollazzo, Bianca Maria; Di Giorgio, Angelo

    2016-06-01

    An integrated treatment strategy using peritonectomy procedures plus hyperthermic intraperitoneal chemotherapy (HIPEC) is now a clinical standard of care in selected patients with peritoneal metastases and primary peritoneal tumors. This comprehensive approach can offer many patients, who hitherto had no hope of cure, a good quality of life and survival despite limited morbidity. The increasingly successful results and chance of interfering in the natural history of disease has prompted research to develop for some clinical conditions a therapeutic strategy designed to prevent malignant peritoneal dissemination before it becomes clinically evident and treat it microscopically (tertiary prevention). The main factor governing successful cytoreductive surgery and predicting outcome is the extent of peritoneal spread assessed with the peritoneal cancer index (PCI). In peritoneal metastases from colorectal and gastric cancer the PCI score acquires a specific role acting as the cut-off between patients who can undergo curative surgery or palliation. Long-term results show that the only group enjoying favorable results are patients with limited disease (a statistical minority). By applying to appropriately selected patients with primary malignancies a proactive management strategy including HIPEC we can treat patients with microscopic peritoneal dissemination and therefore at PCI 0. Among treated conditions pseudomyxoma peritonei enjoys the best results. But a major future advance comes from identifying among lesions at major risk of pseudomyxoma. PMID:27065712

  1. SU-E-T-536: LINAC-Based Single Isocenter Frameless SRT for Brain Metastases

    SciTech Connect

    Liu, B; Zhang, L; Rigor, N; Kim, J

    2015-06-15

    Purpose: Single-isocenter Stereotactic Radiotherapy of multiple brain metastases with Varian 21 IX LINAC, using Aktina Pinpoint system for patient setup. Methods: In 2014, five single-isocenter RapidArc SRT plans were delivered to five patients with 2 to 8 brain metastases using Varian 21 IX. Aktina Pinpoint system was used for setup and 2mm PTV margin were used. CBCT was acquired before and after the beam delivery. The prescription is 2100 cGy in 3 fractions. Eclipse planning system was used for treatment planning. Depending on the number of metastases and their locations, 1 to 5 coplanar or non coplanar arcs were used. Typically, 2 or 3 arcs are used. IMRT QAs were performed by comparing an A1SL ion chamber point dose measurement in solid water phantom to point dose of the plan; also, based on EPID measurement, 3D spatial dose was calculated using DosimetryCheck software package from MathResolutions Inc. The EPID system has an active area of 40cm by 30cm with 1024 by 768 photodiodes, which corresponds to a resolution of 0.4mm by 0.4mm pixel dimension. Results: for all the plans, at least 95% PTV coverage was achieved for full prescription dose, with plan normalization > 75%. RTOG conformity indices are less than 1.1 and Paddick gradient indices are less than 4.5. The distance from prescription IDL to 50% IDL increases as the number of metastases increases, and it ranges from 0.6mm to 0.8mm. Treatment time varies from 10mins to 30mins, depending on the number of arcs and if the arcs are coplanar. IMRT QA shows that the ion chamber measurement agree with the eclipse calculation within 3%, and 95% of the points passed Gamma, using 3% dose difference and 3mm DTA Conclusion: High quality single isocenter RapidArc SRT plan can be optimized and accurately delivered using Eclipse and Varian 21IX.

  2. DNA methylation and gene deletion analysis of brain metastases in melanoma patients identifies mutually exclusive molecular alterations

    PubMed Central

    Marzese, Diego M.; Scolyer, Richard A.; Roqué, Maria; Vargas-Roig, Laura M.; Huynh, Jamie L.; Wilmott, James S.; Murali, Rajmohan; Buckland, Michael E.; Barkhoudarian, Garni; Thompson, John F.; Morton, Donald L.; Kelly, Daniel F.; Hoon, Dave S. B.

    2014-01-01

    Background The brain is a common target of metastases for melanoma patients. Little is known about the genetic and epigenetic alterations in melanoma brain metastases (MBMs). Unraveling these molecular alterations is a key step in understanding their aggressive nature and identifying novel therapeutic targets. Methods Genome-wide DNA methylation analyses of MBMs (n = 15) and normal brain tissues (n = 91) and simultaneous multigene DNA methylation and gene deletion analyses of metastatic melanoma tissues (99 MBMs and 43 extracranial metastases) were performed. BRAF and NRAS mutations were evaluated in MBMs by targeted sequencing. Results MBMs showed significant epigenetic heterogeneity. RARB, RASSF1, ESR1, APC, PTEN, and CDH13 genes were frequently hypermethylated. Deletions were frequently detected in the CDKN2A/B locus. Of MBMs, 46.1% and 28.8% had BRAF and NRAS missense mutations, respectively. Compared with lung and liver metastases, MBMs exhibited higher frequency of CDH13 hypermethylation and CDKN2A/B locus deletion. Mutual exclusivity between hypermethylated genes and CDKN2A/B locus deletion identified 2 clinically relevant molecular subtypes of MBMs. CDKN2A/B deletions were associated with multiple MBMs and frequently hypermethylated genes with shorter time to brain metastasis. Conclusions Melanoma cells that colonize the brain harbor numerous genetically and epigenetically altered genes. This study presents an integrated genomic and epigenomic analysis that reveals MBM-specific molecular alterations and mutually exclusive molecular subtypes. PMID:24968695

  3. Stereotactic radiosurgery as therapy for melanoma, renal carcinoma, and sarcoma brain metastases: Impact of added surgical resection and whole-brain radiotherapy

    SciTech Connect

    Rao, Ganesh; Klimo, Paul; Thompson, Clinton J.; Samlowski, Wolfram; Wang, Michael; Watson, Gordon; Shrieve, Dennis; Jensen, Randy L. . E-mail: randy.jensen@hsc.utah.edu

    2006-11-15

    Purpose: Brain metastases of melanoma, renal carcinoma, and sarcoma have traditionally responded poorly to conventional treatments, including surgery and whole-brain radiotherapy (WBRT). Several studies have suggested a beneficial effect of stereotactic radiosurgery (SRS). We evaluated our institutional experience with systematic SRS in patients harboring these 'radioresistant' metastases. Methods and Materials: A total of 68 patients with brain metastases from melanoma, renal carcinoma, and sarcoma underwent SRS with or without WBRT or surgical resection. All patients had Karnofsky performance scores >70, and SRS was performed before the initiation of systemic therapy. The survival time was calculated from the diagnosis of brain metastases using the Kaplan-Meier product-limit method. Statistical significance was calculated using the log-rank test. Factors influencing survival, including surgical resection, WBRT, gender, number of SRS sessions, and histologic type, were evaluated retrospectively using Cox univariate models. Results: The overall median survival was 427 days (14.2 months), which appears superior to the results obtained with conventional WBRT. The addition of neither surgery nor WBRT to SRS provided a statistically significant increase in survival. Conclusion: Our results suggest that patients undergoing SRS for up to five cerebral metastases from 'radioresistant' tumors (melanoma, renal cell carcinoma, and sarcoma) have survival rates comparable to those in other series of more selected patients. The addition of surgical resection or WBRT did not result in improved survival in our series.

  4. [A Case of Effective Whole-Brain Irradiation and Lapatinib/Capecitabine Combination Therapy for HER2-Positive Breast Cancer with Multiple Brain Metastases].

    PubMed

    Shibasaki, Masayuki; Tanabe, Asami; Toda, Tateo; Sakata, Hiroki; Ijichi, Masayoshi; Kusaka, Kouji; Bandai, Yasutsugu

    2015-06-01

    We report the case of a 48-year-old female patient with HER2-positive and hormone receptor-negative breast cancer with multiple liver metastases. She underwent 6 cycles of FEC followed by docetaxel plus trastuzumab (TZB), resulting in a clinical complete response. After 15 cycles of a TZB-containing regimen, she complained of dizziness and nausea, and imaging examinations revealed multiple brain metastases. Whole-brain irradiation(33.6 Gy) was performed, and the chemotherapy regimen was changed to lapatinib (LAP: orally at 1,250 mg/day, every day) and capecitabine (CAP: orally at 2,000 mg/m2, every day for 2 weeks, followed by a 1-week rest interval, as 1 cycle). After 6 weeks of the new treatment, magnetic resonance imaging revealed marked shrinkage of brain metastases. A clinical complete response was maintained for 19 months. While brain metastasis is an important problem with treatment with TZB, LAP is drawing attention because of its ability to pass the blood-brain barrier because of its small molecular weight. LAP/CAP combination therapy may be an effective treatment option for brain metastases of HER2-positive breast cancer in which TZB essentially has no effect. PMID:26199252

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

    SciTech Connect

    Brennan, Cameron; Yang, T. Jonathan; Hilden, Patrick; Zhang, Zhigang; Chan, Kelvin; Yamada, Yoshiya; Chan, Timothy A.; Lymberis, Stella C.; Narayana, Ashwatha; Tabar, Viviane; Gutin, Philip H.; Ballangrud, Åse; Lis, Eric; Beal, Kathryn

    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

  6. Serum Biomarkers Associated with Clinical Outcomes Fail to Predict Brain Metastases in Patients with Stage IV Non-Small Cell Lung Cancers

    PubMed Central

    Li, Bob T.; Lou, Emil; Hsu, Meier; Yu, Helena A.; Naidoo, Jarushka; Zauderer, Marjorie G.; Sima, Camelia; Johnson, Melissa L.; Daras, Mariza; DeAngelis, Lisa M.; Fleisher, Martin; Kris, Mark G.; Azzoli, Christopher G.

    2016-01-01

    Background Lung cancers account for the majority of brain metastases which pose major therapeutic challenges. Biomarkers prognosticating for the development of brain metastases in patients with non-small cell lung cancers (NSCLC) may improve personalized care. Six serum proteomic biomarkers were previously investigated at Memorial Sloan Kettering but their associations with brain metastases were unknown. Methods Serum NSE, CYFRA 21–1, ProGRP, SCC-Ag, TIMP1, and HE4 by ELISA-based proteomic assays were prospectively collected from consecutive patients with stage IV NSCLC. Pre-treatment serum biomarker levels as well as age, histology, and epidermal growth factor receptor (EGFR) mutation status were evaluated for association with the baseline presence of brain metastases using logistic regression and multivariable analysis. For patients without brain metastases at baseline, the cumulative incidence of subsequent brain metastases were compared according to baseline biomarkers and clinical factors using Gray’s test. Results A total of 118 patients were enrolled, 31 (26%; 95% CI 0.19–0.35) had brain metastases at baseline and a further 26 (22%; 95% CI 0.15–0.30) developed brain metastases subsequently. Pre-treatment serum biomarker levels were available in 104 patients. There was no significant association between the six serum biomarkers and the baseline presence or subsequent development of brain metastases. Age younger than 65 years was the only clinical factor significantly associated with brain metastasis at baseline (OR 3.00; 95% CI 1.22–7.34, P = 0.02) by multivariable analysis. A trend toward increased cumulative incidence of subsequent brain metastases was observed in patients with EGFR mutation (p = 0.2), but this was not statistically significant possibly due to small sample size. Conclusions Serum NSE, CYFRA 21–1, Pro-GRP, SCC-Ag, TIMP1, and HE4 are not significantly associated with brain metastases. Our methods taking into account follow-up time

  7. The Effect of Contouring Variability on Dosimetric Parameters for Brain Metastases Treated With Stereotactic Radiosurgery

    SciTech Connect

    Stanley, Julia; Dunscombe, Peter; Lau, Harold; Burns, Paul; Lim, Gerald; Liu, Hong-Wei; Nordal, Robert; Starreveld, Yves; Valev, Boris; Voroney, Jon-Paul; Spencer, David P.

    2013-12-01

    Purpose: To quantify the effect of contouring variation on stereotactic radiosurgery plan quality metrics for brain metastases. Methods and Materials: Fourteen metastases, each contoured by 8 physicians, formed the basis of this study. A template-based dynamic conformal 5-arc dose distribution was developed for each of the 112 contours, and each dose distribution was applied to the 7 other contours in each patient set. Radiation Therapy Oncology Group (RTOG) plan quality metrics and the Paddick conformity index were calculated for each of the 896 combinations of dose distributions and contours. Results: The ratio of largest to smallest contour volume for each metastasis varied from 1.25 to 4.47, with a median value of 1.68 (n=8). The median absolute difference in RTOG conformity index between the value for the reference contour and the values for the alternative contours was 0.35. The variation of the range of conformity index for all contours for a given tumor varied with the tumor size. Conclusions: The high degree of interobserver contouring variation strongly suggests that peer review or consultation should be adopted to standardize tumor volume prescription. Observer confidence was not reflected in contouring consistency. The impact of contouring variability on plan quality metrics, used as criteria for clinical trial protocol compliance, was such that the category of compliance was robust to interobserver effects only 70% of the time.

  8. Initial experience with combined BRAF and MEK inhibition with stereotactic radiosurgery for BRAF mutant melanoma brain metastases.

    PubMed

    Patel, Bindiya G; Ahmed, Kamran A; Johnstone, Peter A S; Yu, Hsiang-Hsuan Michael; Etame, Arnold B

    2016-08-01

    The combined use of the BRAF inhibitor dabrafenib and MEK inhibitor trametinib has been found to improve survival over dabrafenib alone. The management of melanoma brain metastases continues to present challenges. In this study, we report our initial experience in the management of melanoma brain metastases with stereotactic radiosurgery (SRS) with the use of BRAF and MEK inhibitors. We identified six patients treated with SRS for 17 brain metastases within 3 months of BRAF and MEK inhibitor administration. The median planning target volume was 0.42 cm (range: 0.078-2.08 cm). The median treatment dose was 21 Gy (range 18-24 Gy). The median follow-up of all lesions from SRS was 10.6 months (range 5.8-28.5 months). One lesion was found to undergo local failure 21.7 months following SRS treatment. The median overall survival was 20.0 months (range 6.1-31.8 months) from the time of SRS treatment and 23.1 months (range: 12.1-30.9 months) from the date of BRAFi and MEKi administration. There was no evidence of increased nor unexpected toxicity with the two modalities combined. In this initial experience of melanoma brain metastases treated with BRAF and MEK inhibition with SRS, we find the two modalities can be combined safely. These outcomes should be assessed further in prospective evaluations. PMID:26926151

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

    PubMed

    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. PMID:27405041

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

    PubMed Central

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

    2016-01-01

    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. PMID:27274284

  11. Afatinib-refractory brain metastases from EGFR-mutant non-small-cell lung cancer successfully controlled with erlotinib: a case report.

    PubMed

    Nonagase, Yoshikane; Okamoto, Kunio; Iwasa, Tsutomu; Yoshida, Takeshi; Tanaka, Kaoru; Takeda, Masayuki; Kaneda, Hiroyasu; Shimizu, Toshio; Tsurutani, Junji; Nakagawa, Kazuhiko

    2016-03-01

    Both afatinib and erlotinib are tyrosine kinase inhibitors that inhibit aberrant epidermal growth factor receptor (EGFR) signals in non-small-cell lung cancer (NSCLC). Afatinib is an irreversible inhibitor directed against EGFR, ErbB-2, and ErbB-4, whereas erlotinib is a reversible inhibitor directed against EGFR only. Although afatinib has been shown to be effective in the treatment for erlotinib-refractory and/or gefitinib-refractory central nervous system metastases from NSCLC, little is known about the efficacy of erlotinib for afatinib-refractory central nervous system metastases. In the present report we describe a case of EGFR mutation-positive NSCLC in which brain metastases developed during first-line afatinib treatment. Whole-brain radiation therapy and substitution of erlotinib for afatinib led to successful shrinkage of the brain metastases. Our report highlights the potential benefit of erlotinib for the management of brain metastases refractory over afatinib in patients with NSCLC. PMID:26575001

  12. Management of Brain Metastases in ALK-Positive Non-Small-Cell Lung Cancer.

    PubMed

    Rusthoven, Chad G; Doebele, Robert C

    2016-08-20

    The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 54-year-old man with a former 15-pack-year smoking history presents with cough and dyspnea. Initial work-up with imaging demonstrates a right suprahilar mass measuring 4.7 cm as well as several enlarged hilar and ipsilateral mediastinal lymph nodes. Bronchoscopy with biopsy reveals adenocarcinoma consistent with a lung primary. Staging with positron emission tomography/computed tomography (PET/CT) reidentifies the primary mass and lymph nodes and shows several PET-avid bone metastases. Brain magnetic resonance imaging (MRI) demonstrates a 1.6-cm right parietal mass with mild vasogenic edema and four additional brain metastases measuring 4 to 9 mm in size. Molecular testing is positive for an anaplastic lymphoma kinase (ALK) gene rearrangement using fluorescence in situ hybridization and negative for EGFR, ROS1, RET, BRAF, KRAS, and other oncogenes. The patient denies any neurologic symptoms and has no significant findings on neurologic exam. He is referred to you for management options for newly diagnosed stage IV (T2aN2M1b) lung adenocarcinoma. PMID:27298405

  13. Frameless Image-Guided Intracranial Stereotactic Radiosurgery: Clinical Outcomes for Brain Metastases

    SciTech Connect

    Breneman, John C. Steinmetz, Ryan; Smith, Aaron; Lamba, Michael; Warnick, Ronald E.

    2009-07-01

    Purpose: After preclinical investigations confirming the accuracy of target localization by frameless image-guided radiosurgery, we report the clinical outcomes of patients with brain metastases who underwent frameless radiosurgery. Methods and Materials: Between 2005 and 2006, 53 patients underwent frameless stereotactic radiosurgery using a linear accelerator equipped with on-board image guidance for the treatment of 158 brain metastases. The radiation doses were delivered in a single fraction (dose range, 12-22 Gy; median, 18). Patients were followed with magnetic resonance imaging scans at 2-3-month intervals. Progression-free survival was the primary study endpoint. Results: With a median follow-up of 38 weeks (range, 14-112), the overall survival rate was 70% at 6 months, 44% at 1 year, 29% at 18 months, and 16% at 24 months. Local control was achieved in 90% of 168 treated lesions at 6 months, 80% at 12 months, 78% at 18 months, and 78% at 24 months. Local control tended to be improved in lesions treated with {>=}18 Gy and for lesions <0.2 cm{sup 3}. Adverse events occurred in 5 patients (9.6%). No evidence of imaging changes on post-stereotactic radiosurgery scans was found to suggest mistargeting of a radiation isocenter. Conclusion: The clinical outcomes after frameless stereotactic radiosurgery were comparable to those after frame-based radiosurgery techniques. Given its significant advantages in terms of patient comfort, ability to use fractionated treatment regimens, and convenience in scheduling of personnel and equipment resources, frameless radiosurgery will likely become a common technique for intracranial radiosurgery.

  14. Pemetrexed/cisplatin as first-line chemotherapy for advanced lung cancer with brain metastases

    PubMed Central

    He, Guangzhao; Xiao, Xiaoguang; Zou, Man; Zhang, Chengliang; Xia, Shu

    2016-01-01

    Abstract Background: Brain metastases (BMs) are a common and serious complication of non-small cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT), surgery, and molecular targeted therapy are usually used to treat NSCLC with BM. Chemotherapeutic options for BM are limited by tumor resistance, ineffective agents, and the blood–brain barrier. Pemetrexed/cisplatin is the preferred chemotherapy in nonsquamous NSCLC, but the efficacy of this treatment for nonsquamous NSCLC with BM is uncertain. Methods: We present a case of nonsquamous NSCLC with asymptomatic BM presenting with irritating cough and right shoulder back pain (unknown sensitizing epidermal growth factor receptor mutations or anaplastic lymphoma kinase). Results: He benefited from administration of first-line chemotherapy of pemetrexed/cisplatin. Partial remission was achieved in the primary lesion of the lungs and BM lesion. He was further given 3 cycles of pemetrexed monotherapy and WBRT. Complete remission was further achieved in BM lesion. Conclusion: The findings of clinical trials and theoretical studies about the current pemetrexed/cisplatin in the treatment of nonsquamous NSCLC with BM are also summarized to provide a reference for the application of pemetrexed/cisplatin in nonsquamous NSCLC with BM. Whether or not pemetrexed/cisplatin is definitely effective in nonsquamous NSCLC with BM must be proven by subsequent phase III clinical trials. PMID:27512852

  15. Breast cancer brain metastases responding to lapatinib plus capecitabine as second-line primary systemic therapy.

    PubMed

    Bergen, Elisabeth S; Berghoff, Anna S; Rudas, Margaretha; Preusser, Matthias; Bartsch, Rupert

    2015-06-01

    Brain metastases (BM) are diagnosed in up to 40% of HER2-positive breast cancer patients. Standard treatment includes local approaches such as whole-brain radiotherapy (WBRT), radiosurgery, and neurosurgery. The landscape trial established primary systemic therapy as an effective and safe alternative to WBRT in selected patients with Her2-positive BM. We aim to further focus on the role of systemic therapy in oligosymptomatic patients by presenting this case report. We report on a 50-year-old patient diagnosed with multiple BM 5 years after early breast cancer diagnosis. As the patient was asymptomatic and had a favorable diagnosis-specific GPA score, she received primary systemic treatment with T-DM1. She achieved partial remission within the brain for eight treatment cycles and then progressed despite stable extracranial disease. As the patient remained asymptomatic and refused WBRT, we decided upon trastuzumab, lapatinib plus capecitabine as second-line therapy. Another partial remission of BM was observed; to date, she has received 11 treatment cycles without any sign of disease progression. In this case, WBRT was delayed by at least 14 months, again indicating the activity of systemic treatment in BM. Apparently, in selected patients, BM can be controlled with multiple lines of systemic therapy similar to extracranial disease. Further investigation of systemic treatment approaches is therefore warranted. PMID:25714248

  16. Treatment of brain metastases from HER-2-positive breast cancer: current status and new concepts.

    PubMed

    Bartolotti, Marco; Franceschi, Enrico; Brandes, Alba A

    2013-11-01

    Breast cancer is the second most common source of brain metastases (BM). The incidence of BM in breast cancer patients has increased over the past decade, especially among patients with HER-2-positive breast cancer. This is probably due to how aggressive the HER-2-positive disease is but also to the prolongation of survival obtained with current treatments, which allow good control of extracranial disease but are unable to cross the blood-brain barrier. At present, whole-brain radiotherapy, surgery and radiosurgery/stereotactic radiotherapy represent the cornerstone of treatment for BM, while the role of pharmacological therapy remains uncertain. Lapatinib demonstrated activity against BM from HER-2-positive breast cancer in small Phase II and retrospective studies, mainly in combination with capecitabine, and cases of dramatic responses to such treatment are present in literature. In this review we focus on the available clinical data regarding the treatment of BM from HER-2-positive breast cancer and on new concepts about the treatment and evaluation of the CNS response. PMID:24156325

  17. Breast Cancer With Brain Metastases: Clinicopathologic Features, Survival, and Paired Biomarker Analysis

    PubMed Central

    Shen, Qi; Hess, Kenneth R.; Suki, Dima; Aldape, Kenneth D.; Sawaya, Raymond; Ibrahim, Nuhad K.

    2015-01-01

    Background. The aim of this study was to describe clinicopathologic features of patients with breast cancer brain metastasis (BCBM); to evaluate survival after diagnosis of BCBM; and to compare estrogen receptor (ER), progesterone receptor (PR), and HER2 expression in the paired primary and brain tumors. Materials and Methods. We identified 140 consecutive patients who underwent craniotomy for BCBM (either for diagnostic purpose or with therapeutic intent) at the University of Texas MD Anderson Cancer Center between 2002 and 2009. Results. Most patients had invasive ductal histology (91%), grade 3 tumors (67%), and positive axillary lymph node (64%). Of the tumors, 56% were ER-negative, 62% were PR-negative, 44% were HER2-positive, and 28% were triple negative (TN). Brain metastasis (BM) was solitary in 51% of patients. Median interval from breast cancer diagnosis to BM was 46 months; median survival after BM was 14.1 months. In the univariate analysis, younger age, solitary brain metastasis, and ER or PR positivity in the breast tumors were associated with longer survival. There was a statistical trend toward increased survival in HER2-positive patients compared with HER2-negative patients (18 vs. 11 months). In the multivariate analysis, predictors for longer survival included younger age, solitary brain lesion, and HER2 positivity in the breast cancer. Biomarkers were evaluated in paired primary and brain tumors in 35 patients for ER status, 34 for PR status, and 36 for HER2 status. Discordant rates were 28% for ER, 20% for PR, and 3% for HER2. Conclusion. Compared with unselected breast cancer patients at the same institution, patients with breast cancer who had brain metastases had a higher proportion of hormone receptor-negative, HER2-positive, and TN tumors. Younger age, solitary brain lesion, and HER2 expression were independent predictors of better survival in patients with BCBM. HER2 status was highly concordant between the paired primary and brain tumors

  18. Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

    SciTech Connect

    Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas; Shi, Weiji; Riely, Gregory J.; Beal, Kathryn; Yu, Helena A.; Chan, Timothy A.; Zhang, Zhigang; Wu, Abraham J.

    2014-06-01

    Purpose/Objectives: Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials: Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results: 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004). Conclusions: The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system activity.

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

    SciTech Connect

    Minniti, Giuseppe; Esposito, Vincenzo; Clarke, Enrico; Scaringi, Claudia; Lanzetta, Gaetano; Salvati, Maurizio; Raco, Antonino; Bozzao, Alessandro; Maurizi Enrici, Riccardo

    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.

  20. Dose-Volume Response Relationship for Brain Metastases Treated with Frameless Single-Fraction Linear Accelerator-Based Stereotactic Radiosurgery

    PubMed Central

    Pan, Jianmin; Yusuf, Mehran B; Dragun, Anthony; Dunlap, Neal; Guan, Timothy; Boling, Warren; Rai, Shesh; Woo, Shiao

    2016-01-01

    Background: Our aim was to identify a dose-volume response relationship for brain metastases treated with frameless stereotactic radiosurgery (SRS). Methods: We reviewed patients who underwent frameless single-fraction linear accelerator SRS for brain metastases between 2007 and 2013 from an institutional database. Proportional hazards modeling was used to identify predictors of outcome. A ratio of maximum lesion dose per mm-diameter (Gy/mm) was constructed to establish a dose-volume relationship. Results: There were 316 metastases evaluated in 121 patients (2 - 33 mm in the largest diameter). The median peripheral dose was 18.0 Gy (range: 10.0 – 24.0 Gy). Local control was 84.8% for all lesions and was affected by location, peripheral dose, maximum dose, and lesion size (p values < 0.050). A dose-volume response relationship was constructed using the maximum dose and lesion size. A unit increase in Gy/mm was associated with decreased local failure (p = 0.005). Local control of 80%, 85%, and 90% corresponded to maximum doses per millimeter of 1.67 Gy/mm, 2.86 Gy/mm, and 4.4 Gy/mm, respectively. Toxicity was uncommon and only 1.0% of lesions developed radionecrosis requiring surgery. Conclusions: For brain metastases less than 3 cm, a dose-volume response relationship exists between maximum radiosurgical dose and lesion size, which is predictive of local control. PMID:27284495

  1. [Two patients having recurrent breast cancer with brain metastases well controlled with a gamma knife radio-surgery].

    PubMed

    Hojo, Shigeyuki; Maeura, Yoshiichi; Yoshioka, Setsuko; Fujie, Yujiro; Fukunaga, Hiroki; Okada, Yoshihiro; Ota, Hirofumi; Endo, Wakio

    2006-11-01

    We report two patients having recurrent breast cancer with brain metastases that was controlled well with a gamma knife radio-surgery. The patient is a 50-year-old woman. She underwent radical mastectomy for right breast cancer in September 1993. She suffered from multiple liver metastases in June 2000, so CEF therapy contained hepatic arterial infusion chemotherapy, and extended right lobectomy of the liver were performed in December 2001. Afterward, pleurodesis was carried out to the carcinomatous pleurisy. Then she underwent simple total hysterectomy and bilateral oophorectomy for torsion of the metastatic ovarian tumor. MRI study revealed brain metastases with a diameter of 1 cm in her right midbrain in April 2005, so a gamma knife radio-surgery was performed. After the radio-surgery, a weekly paclitaxel therapy followed by peroral chemotherapy with capecitabine was started, and she took the regimen continuously. Another patient is a 56-year-old woman. She underwent skin sparing mastectomy with axillary lymph node dissection for right breast cancer in November 2002. Metastases to the base of her skull were found in October 2004, so a gamma knife radio-surgery was carried out. After the radio-surgery, a weekly paclitaxel therapy with anastrozole was started. In both of the two patients, the metastatic brain tumors have not shown growth so far and are under good control as of March 2006. PMID:17212144

  2. Brain metastases from solid tumors: disease outcome according to type of treatment and therapeutic resources of the treating center

    PubMed Central

    2011-01-01

    Background To evaluate the therapeutic strategies commonly employed in the clinic for the management of brain metastases (BMs) and to correlate disease outcome with type of treatment and therapeutic resources available at the treating center. Methods Four Cancer centres participated to the survey. Data were collected through a questionnaire filled in by one physician for each centre. Results Clinical data regarding 290 cancer patients with BMs from solid tumors were collected. Median age was 59 and 59% of patients had ≤ 3 brain metastases. A local approach (surgery and stereotactic radiosurgery) was adopted in 31% of patients. The local approach demonstrated to be superior in terms of survival compared to the regional/systemic approach (whole brain radiotherapy and chemotherapy, p = <.0001 for survival at 2 years). In the multivariate analysis local treatment was an independent prognostic factor for survival. When patients were divided into 2 groups whether they were treated in centers where local approaches were available or not (group A vs group B respectively, 58% of patients with ≤ 3 BMs in both cohorts), more patients in group A received local strategies although no difference in time to brain progression at 1 year was observed between the two groups of patients. Conclusions In clinical practice, local strategies should be integrated in the management of brain metastases. Proper selection of patients who are candidate to local treatments is of crucial importance. PMID:21244695

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

    SciTech Connect

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

    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. A pure non-gestational ovarian choriocarcinoma with delayed solitary brain metastases: Case report and review of the literature.

    PubMed

    Rao, K V L Narasinga; Konar, Subhas; Gangadharan, Jagathlal; Vikas, V; Sampath, S

    2015-01-01

    Choriocarcinoma is the most malignant tumour of gestational trophoblastic origin. Most ovarian choriocarcinomas are gestational in origin and usually metastasize to the ovary from uterine or tubal choriocarcinoma. Non gestational choriocarcinoma (NGOC) of the ovary is exceedingly rare and usually seen along with other germ cell tumors. Non gestational choriocarcinoma has been found to be resistant to single-agent chemotherapy and has a worse prognosis than gestational choriocarcinoma. We are reporting long term follow up of published rare case of pure non gestational ovarian choriocarcinoma (NGOC) with concurrent metastases to the spleen and adrenal glands, who developed a delayed solitary brain metastases, two years after completion of primary treatment. Surgery along with triple agent chemotherapy and radiotherapy was found to give good remission in this aggressive disease. PMID:26752905

  5. Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases?

    PubMed

    Colaco, Rovel J; Martin, Pierre; Kluger, Harriet M; Yu, James B; Chiang, Veronica L

    2016-07-01

    OBJECT Radiation necrosis (RN), or its imaging equivalent, treatment-related imaging changes (TRIC), is an inflammatory reaction to high-dose radiation in the brain. The authors sought to investigate the hypothesis that immunotherapy increases the risk of developing RN/TRIC after stereotactic Gamma Knife (GK) radiosurgery for brain metastases. METHODS A total of 180 patients who underwent GK surgery for brain metastases between 2006 and 2012 were studied. The systemic therapy they received was classified as cytotoxic chemotherapy (CT), targeted therapy (TT), or immunotherapy (IT). The timing of systemic therapy in relation to GK treatment was also recorded. Logistic regression was used to calculate the odds of developing RN according to type of systemic therapy received. RESULTS The median follow-up time was 11.7 months. Of 180 patients, 39 (21.7%) developed RN/TRIC. RN/TRIC rates were 37.5% (12 of 32) in patients who received IT alone, 16.9% (14 of 83) in those who received CT only, and 25.0% (5 of 20) in those who received TT only. Median overall survival was significantly longer in patients who developed RN/TRIC (23.7 vs 9.9 months, respectively). The RN/TRIC rate was increased significantly in patients who received IT alone (OR 2.40 [95% CI 1.06-5.44]; p = 0.03), whereas receipt of any CT was associated with a lower risk of RN/TRIC (OR 0.38 [95% CI 0.18-0.78]; p = 0.01). The timing of development of RN/TRIC was not different between patients who received IT and those who received CT. CONCLUSIONS Patients who receive IT alone may have an increased rate of RN/TRIC compared with those who receive CT or TT alone after stereotactic radiosurgery, whereas receiving any CT may in fact be protective against RN/TRIC. As the use of immunotherapies increases, the rate of RN/TRIC may be expected to increase compared with rates in the chemotherapy era. PMID:26544782

  6. Tumor Bed Dynamics After Surgical Resection of Brain Metastases: Implications for Postoperative Radiosurgery

    SciTech Connect

    Jarvis, Lesley A.; Simmons, Nathan E.; Bellerive, Marc; Erkmen, Kadir; Eskey, Clifford J.; Gladstone, David J.; Hug, Eugen B.; Roberts, David W.; Hartford, Alan C.

    2012-11-15

    Purpose: To analyze 2 factors that influence timing of radiosurgery after surgical resection of brain metastases: target volume dynamics and intracranial tumor progression in the interval between surgery and cavity stereotactic radiosurgery (SRS). Methods and Materials: Three diagnostic magnetic resonance imaging (MRI) scans were retrospectively analyzed for 41 patients with a total of 43 resected brain metastases: preoperative MRI scan (MRI-1), MRI scan within 24 hours after surgery (MRI-2), and MRI scan for radiosurgery planning, which is generally performed {<=}1 week before SRS (MRI-3). Tumors were contoured on MRI-1 scans, and resection cavities were contoured on MRI-2 and MRI-3 scans. Results: The mean tumor volume before surgery was 14.23 cm{sup 3}, and the mean cavity volume was 8.53 cm{sup 3} immediately after surgery and 8.77 cm{sup 3} before SRS. In the interval between surgery and SRS, 20 cavities (46.5%) were stable in size, defined as a change of {<=}2 cm{sup 3}; 10 cavities (23.3%) collapsed by >2 cm{sup 3}; and 13 cavities (30.2%) increased by >2 cm{sup 3}. The unexpected increase in cavity size was a result of local progression (2 cavities), accumulation of cyst-like fluid or blood (9 cavities), and nonspecific postsurgical changes (2 cavities). Finally, in the interval between surgery and SRS, 5 cavities showed definite local tumor progression, 4 patients had progression elsewhere in the brain, 1 patient had both local progression and progression elsewhere, and 33 patients had stable intracranial disease. Conclusions: In the interval between surgical resection and delivery of SRS, surgical cavities are dynamic in size; however, most cavities do not collapse, and nearly one-third are larger at the time of SRS. These observations support obtaining imaging for radiosurgery planning as close to SRS delivery as possible and suggest that delaying SRS after surgery does not offer the benefit of cavity collapse in most patients. A prospective, multi

  7. EGFR, KRAS, BRAF, and HER-2 molecular status in brain metastases from 77 NSCLC patients

    PubMed Central

    Villalva, Claire; Duranton-Tanneur, Valérie; Guilloteau, Karline; Burel-Vandenbos, Fanny; Wager, Michel; Doyen, Jérôme; Levillain, Pierre Marie; Fontaine, Denys; Blons, Hélène; Pedeutour, Florence; Karayan-Tapon, Lucie

    2013-01-01

    The aim of this study was to determine the frequency of EGFR, KRAS, BRAF, and HER-2 mutations in brain metastases from non-small cell lung carcinomas (BM-NSCLC). A total of 77 samples of BM-NSCLC were included and 19 samples of BM from breast, kidney, and colorectal tumors were also studied as controls. These samples were collected from patients followed between 2008 and 2011 at Poitiers and Nice University Hospitals in France. The frequencies of EGFR, KRAS, BRAF, and HER-2 mutations in BM-NSCLC were 2.6, 38.5, 0, and 0% respectively. The incidence of KRAS mutation was significantly higher in female and younger patients (P < 0.05). No mutations of the four genes were found in BM from breast or kidney. However, among six BM from colorectal tumors, we identified KRAS mutations in three cases and BRAF mutations in two other cases. This study is the largest analysis on genetic alterations in BM-NSCLC performed to date. Our results suggest a low frequency of EGFR mutations in BM-NSCLC whereas KRAS mutations are as frequent in BM-NSCLC as in primitive NSCLC. These results raise the question of the variability of the brain metastatic potential of NSCLC cells in relation to the mutation pattern. PMID:23930206

  8. Irinotecan and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases From Solid Tumors

    ClinicalTrials.gov

    2010-03-15

    Brain and Central Nervous System Tumors; Cognitive/Functional Effects; Long-term Effects Secondary to Cancer Therapy in Adults; Long-term Effects Secondary to Cancer Therapy in Children; Poor Performance Status; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  9. A Phase I Study of Short-Course Accelerated Whole Brain Radiation Therapy for Multiple Brain Metastases

    SciTech Connect

    Caravatta, Luciana; Deodato, Francesco; Ferro, Marica; Macchia, Gabriella; Massaccesi, Mariangela; Cilla, Savino; Padula, Gilbert D.A.; Mignogna, Samantha; Tambaro, Rosa; Carrozza, Francesco; Flocco, Mariano; Cantore, Giampaolo; Scapati, Andrea; Buwenge, Milly; and others

    2012-11-15

    Purpose: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. Methods and Materials: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class > or =2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status {<=}3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity {>=}grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. Results: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). Conclusions: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

  10. Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis

    PubMed Central

    Zhao, Qian; Qin, Qin; Sun, Jinglong; Han, Dan; Wang, Zhongtang; Teng, Junjie; Li, Baosheng

    2016-01-01

    Objective We performed a meta-analysis of randomized clinical trials to compare the efficacy of brain radiotherapy (RT) combined with temozolomide (TMZ) versus RT alone as first-line treatment for brain metastases (BM). Methods Medline, Embase, and Pubmed were used to search for relevant randomized controlled trials (RCTs). Two investigators reviewed the abstracts and independently rated the quality of trials and relevant data. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and adverse events. Results Seven studies were selected from the literature search. RT plus TMZ produced significant improvement in ORR with odds ratio (OR) of 2.27 (95% CI, 1.29 to 4.00; P = 0.005) compared with RT alone. OS and PFS were not significantly different between the two arms (OS: HR, 1.00; P = 0.959; PFS: HR, 0.73; P = 0.232). However, the RT plus TMZ arm was associated with significantly more grade 3 to 4 nausea and thrombocytopenia. Conclusion Concomitant RT and TMZ, compared to RT alone, significantly increases ORR in patients with BM, but yields increased toxicity and fails to demonstrate a survival advantage. PMID:26930609

  11. What do patients with brain metastases from non-small cell lung cancer want from their treatment?

    PubMed

    Dorman, S; Hayes, J; Pease, N

    2009-10-01

    Brain metastases are a common complication of non-small cell lung cancer (NSCLC). Prognosis is poor and the effectiveness of whole brain radiotherapy (WBRT) is uncertain for patients with moderate performance status. Studies on WBRT effectiveness have thus far used outcome measures, such as survival, performance status and cognitive function. The aim of this study was to study what patients with recently diagnosed brain metastases from NSCLC want from their treatment. We carried out semistructured interviews with nine patients with brain metastases from NSCLC, for whom the benefit of WBRT is uncertain. Interpretative phenomenological analysis was used. Themes identified included quality versus quantity of life, factors contributing to quality of life (including family, mobility and normality), 'Go for it!' - the desire to try anything, the desire for a cure or 'magic wand', fear and other factors (including family in decision making, information or lack of information, relationship with professionals, experience of steroids and radiotherapy including adverse effects). Quality of life is important to patients, but many are keen to try any treatment which might prolong their life. Understanding patients' values regarding treatment and goals of treatment can help clinicians discuss these issues with patients and provide appropriate information and can aid selection of appropriate outcome measures. PMID:19443522

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

    SciTech Connect

    Dyer, Michael A.; Kelly, Paul J.; Chen, Yu-Hui; Pinnell, Nancy E.; Lee, Eudocia Q.; Arvold, Nils D.; Lin, Nancy U.

    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.

  13. Liver metastases

    MedlinePlus

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases

  14. SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

    SciTech Connect

    Hossain, S; Hildebrand, K; Ahmad, S; Larson, D; Ma, L; Sahgal, A

    2014-06-01

    Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targets were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.

  15. Whole brain radiotherapy plus simultaneous in-field boost with image guided intensity-modulated radiotherapy for brain metastases of non-small cell lung cancer

    PubMed Central

    2014-01-01

    Background Whole brain radiotherapy (WBRT) plus sequential focal radiation boost is a commonly used therapeutic strategy for patients with brain metastases. However, recent reports on WBRT plus simultaneous in-field boost (SIB) also showed promising outcomes. The objective of present study is to retrospectively evaluate the efficacy and toxicities of WBRT plus SIB with image guided intensity-modulated radiotherapy (IG-IMRT) for inoperable brain metastases of NSCLC. Methods Twenty-nine NSCLC patients with 87 inoperable brain metastases were included in this retrospective study. All patients received WBRT at a dose of 40 Gy/20 f, and SIB boost with IG-IMRT at a dose of 20 Gy/5 f concurrent with WBRT in the fourth week. Prior to each fraction of IG-IMRT boost, on-line positioning verification and correction were used to ensure that the set-up errors were within 2 mm by cone beam computed tomography in all patients. Results The one-year intracranial control rate, local brain failure rate, and distant brain failure rate were 62.9%, 13.8%, and 19.2%, respectively. The two-year intracranial control rate, local brain failure rate, and distant brain failure rate were 42.5%, 30.9%, and 36.4%, respectively. Both median intracranial progression-free survival and median survival were 10 months. Six-month, one-year, and two-year survival rates were 65.5%, 41.4%, and 13.8%, corresponding to 62.1%, 41.4%, and 10.3% of intracranial progression-free survival rates. Patients with Score Index for Radiosurgery in Brain Metastases (SIR) >5, number of intracranial lesions <3, and history of EGFR-TKI treatment had better survival. Three lesions (3.45%) demonstrated radiation necrosis after radiotherapy. Grades 2 and 3 cognitive impairment with grade 2 radiation leukoencephalopathy were observed in 4 (13.8%) and 4 (13.8%) patients. No dosimetric parameters were found to be associated with these late toxicities. Patients received EGFR-TKI treatment had higher incidence of grades 2–3

  16. Diagnosis of Brain Metastases from Lung Cancer Using a Modified Electromagnetism like Mechanism Algorithm.

    PubMed

    Chen, Kun-Huang; Wang, Kung-Jeng; Adrian, Angelia Melani; Wang, Kung-Min; Teng, Nai-Chia

    2016-01-01

    Brain metastases are commonly found in patients that are diagnosed with primary malignancy on their lung. Lung cancer patients with brain metastasis tend to have a poor survivability, which is less than 6 months in median. Therefore, an early and effective detection system for such disease is needed to help prolong the patients' survivability and improved their quality of life. A modified electromagnetism-like mechanism (EM) algorithm, MEM-SVM, is proposed by combining EM algorithm with support vector machine (SVM) as the classifier and opposite sign test (OST) as the local search technique. The proposed method is applied to 44 UCI and IDA datasets, and 5 cancers microarray datasets as preliminary experiment. In addition, this method is tested on 4 lung cancer microarray public dataset. Further, we tested our method on a nationwide dataset of brain metastasis from lung cancer (BMLC) in Taiwan. Since the nature of real medical dataset to be highly imbalanced, the synthetic minority over-sampling technique (SMOTE) is utilized to handle this problem. The proposed method is compared against another 8 popular benchmark classifiers and feature selection methods. The performance evaluation is based on the accuracy and Kappa index. For the 44 UCI and IDA datasets and 5 cancer microarray datasets, a non-parametric statistical test confirmed that MEM-SVM outperformed the other methods. For the 4 lung cancer public microarray datasets, MEM-SVM still achieved the highest mean value for accuracy and Kappa index. Due to the imbalanced property on the real case of BMLC dataset, all methods achieve good accuracy without significance difference among the methods. However, on the balanced BMLC dataset, MEM-SVM appears to be the best method with higher accuracy and Kappa index. We successfully developed MEM-SVM to predict the occurrence of brain metastasis from lung cancer with the combination of SMOTE technique to handle the class imbalance properties. The results confirmed that MEM

  17. Subclassification of Recursive Partitioning Analysis Class II Patients With Brain Metastases Treated Radiosurgically

    SciTech Connect

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

    2012-08-01

    Purpose: Although the recursive partitioning analysis (RPA) class is generally used for predicting survival periods of patients with brain metastases (METs), the majority of such patients are Class II and clinical factors vary quite widely within this category. This prompted us to divide RPA Class II patients into three subclasses. Methods and Materials: This was a two-institution, institutional review board-approved, retrospective cohort study using two databases: the Mito series (2,000 consecutive patients, comprising 787 women and 1,213 men; mean age, 65 years [range, 19-96 years]) and the Chiba series (1,753 patients, comprising 673 female and 1,080 male patients; mean age, 65 years [range, 7-94 years]). Both patient series underwent Gamma Knife radiosurgery alone, without whole-brain radiotherapy, for brain METs during the same 10-year period, July 1998 through June 2008. The Cox proportional hazard model with a step-wise selection procedure was used for multivariate analysis. Results: In the Mito series, four factors were identified as favoring longer survival: Karnofsky Performance Status (90% to 100% vs. 70% to 80%), tumor numbers (solitary vs. multiple), primary tumor status (controlled vs. not controlled), and non-brain METs (no vs. yes). This new index is the sum of scores (0 and 1) of these four factors: RPA Class II-a, score of 0 or 1; RPA Class II-b, score of 2; and RPA Class II-c, score of 3 or 4. Next, using the Chiba series, we tested whether our index is valid for a different patient group. This new system showed highly statistically significant differences among subclasses in both the Mito series and the Chiba series (p < 0.001 for all subclasses). In addition, this new index was confirmed to be applicable to Class II patients with four major primary tumor sites, that is, lung, breast, alimentary tract, and urogenital organs. Conclusions: Our new grading system should be considered when designing future clinical trials involving brain MET

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

    SciTech Connect

    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

    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.

  19. [A case of effective lapatinib/capecitabine therapy for HER2-positive breast cancer with multiple brain metastases].

    PubMed

    Fujita, Yoshifumi; Mizuta, Naruhiko; Sakaguchi, Koichi; Nakatsukasa, Katsuhiko; Imai, Aya; Umeda, Yoshimi; Hamaoka, Asako; Morita, Midori; Shouji, Mari; Goto, Mariko; Taguchi, Tetsuya

    2012-11-01

    A 63-year-old woman was suffering from HER2-positive and hormone receptor-negative breast cancer with bone metastasis. She received 16 cycles of paclitaxel(PTX 80mg/m2)plus trastuzumab(TRA 2mg/kg)on a 7-day cycle, and zoledronic acid(ZOL 4mg/body every 28 days), resulting in a near clinical complete response(cCR). Two years later, the patient complained of dizziness and nausea, and magnetic resonance imaging revealed multiple brain metastases. The prior treatments with PTX and TRA were changed to lapatinib(LAP)(orally at 1, 250mg/day every day)and capecitabine(CAP)(orally at 2, 000mg/m2 every day for 2 weeks, followed by a 1-week rest interval as 1 cycle)because of the multiple brain metastases. After 4 cycles of treatment, the number of brain lesions and the tumor sizes were significantly reduced. After 7 cycles, however, magnetic resonance imaging revealed the deterioration of some brain lesions. After whole-brain irradiation(30 Gy in 10 fractions)was added to the treatment, the outcome was near cCR. In conclusion, combination therapy of Lap and Cap may be an effective treatment option for brain metastasis of HER2-positive breast cancer. PMID:23152022

  20. Prediction of Clinical Outcomes by Chemokine and Cytokine Profiling In CSF from Radiation Treated Breast Cancer Primary with Brain Metastases

    NASA Astrophysics Data System (ADS)

    Lok, Edwin

    Whole brain radiation is the standard treatment for patients with brain metastasis but unfortunately tumors can recover from radiation-induced damage with the help of the immune system. The hypothesis that differences in immunokines in the cerebrospinal fluid (CSF) pre- and post-irradiation could reveal tumor biology and correlate with outcome of patients with metastatic breast cancer to the brain is tested. Collected CSF samples were analyzed using Luminex's multiplexing assays to survey global immunokine levels while Enzyme-Linked Immunosorbent Assays were used to quantify each individual immunokines. Cluster analysis was performed to segregate patients based on their common immunokine profile and each cluster was correlated with survival and other clinical parameters. Breast cancer brain metastasis was found to have altered immunokine profiles in the CSF, and that Interleukin-1α expression was elevated after irradiation. Therefore, immunokine profiling in the CSF could enable cancer physicians to monitor the status of brain metastases.

  1. Perillyl Alcohol and Its Drug-Conjugated Derivatives as Potential Novel Methods of Treating Brain Metastases.

    PubMed

    Chen, Thomas C; Da Fonseca, Clovis O; Schönthal, Axel H

    2016-01-01

    Metastasis to the central nervous system remains difficult to treat, and such patients are faced with a dismal prognosis. The blood-brain barrier (BBB), despite being partially compromised within malignant lesions in the brain, still retains much of its barrier function and prevents most chemotherapeutic agents from effectively reaching the tumor cells. Here, we review some of the recent developments aimed at overcoming this obstacle in order to more effectively deliver chemotherapeutic agents to the intracranial tumor site. These advances include intranasal delivery to achieve direct nose-to-brain transport of anticancer agents and covalent modification of existing drugs to support enhanced penetration of the BBB. In both of these areas, use of the natural product perillyl alcohol, a monoterpene with anticancer properties, contributed to promising new results, which will be discussed here. PMID:27598140

  2. Radiotherapy of brain metastases from breast cancer: Treatment results and prognostic factors

    PubMed Central

    KÜHNÖL, JULIA; KÜHNÖL, CASPAR; VORDERMARK, DIRK

    2016-01-01

    Brain metastases (BM) from breast cancer are associated with high morbidity and a poor prognosis. The aim of this study was to analyse the role of radiotherapy in treatment of BM from breast cancer in the context of modern local therapy modalities, current systemic treatment options and prognostic factors. A retrospective analysis of 86 consecutive female patients treated with radiotherapy for BM from breast cancer between 2000 and 2010 was conducted. Patient and treatment characteristics were registered and survival data calculated. All patients received whole-brain radiotherapy (WBRT) with a median dose of 36 Gy, and 19 patients were treated with an additional boost; this included fractionated schemes (median dose, 18 Gy) and radiosurgery (5 and 17 Gy). The median overall survival time from the start of WBRT was 4.1 months in the present cohort. Patients receiving a boost survived 19.7 months in comparison to 3.1 months for patients treated with WBRT alone (P<0.001). Other factors that improved overall survival, based on a univariate analysis, were dose of WBRT and number of BM. There was no statistical evidence for the influence of the human epidermal growth factor receptor 2 status on survival in the current study. The administration of boost treatment following WBRT was also identified as a significant factor influencing survival on multivariate analysis (P=0.030). In conclusion, radiotherapy affects the survival time of patients with BM from breast cancer. In particular, the implementation of boost treatment following WBRT in selected patients seems to extend survival time. PMID:27123095

  3. Activity of T-DM1 in Her2-positive breast cancer brain metastases.

    PubMed

    Bartsch, Rupert; Berghoff, Anna S; Vogl, Ursula; Rudas, Margaretha; Bergen, Elisabeth; Dubsky, Peter; Dieckmann, Karin; Pinker, Katja; Bago-Horvath, Zsuzsanna; Galid, Arik; Oehler, Leopold; Zielinski, Christoph C; Gnant, Michael; Steger, Guenther G; Preusser, Matthias

    2015-10-01

    Brain metastases (BM) are frequently diagnosed in metastatic Her2-positive breast cancer. Local treatment remains the standard of care but lapatinib plus capecitabine was recently established as systemic therapy option. Due to a disruption of the blood-brain/tumour-barrier at metastatic sites, even large molecules may penetrate into the central nervous system (CNS). Here, we report on the activity of T-DM1 in Her2-positive breast cancer BM. T-DM1 was administered at a dose of 3.6 mg once every 3 weeks as primary systemic therapy for BM or upon documented CNS progression after initial local treatment. Thus, this study allowed for the appraisal of T-DM1 activity in BM. Restaging was conducted every 12 weeks with MRI or whenever symptoms of disease progression occurred. Ten patients were included; in two asymptomatic subjects, T-DM1 was administered as primary therapy, while eight had progressive BM. All patients had received prior treatment with trastuzumab, six had already received lapatinib, and three pertuzumab as well. Three patients had partial remission of BM, and two patient had stable disease lasting for ≥6 months; two further patients had stable disease for <6 months while three progressed despite treatment. At 8.5 months median follow-up, intracranial PFS was 5 months, and median OS from initiation of T-DM1 was not reached. Local treatment of BM remains the standard of care; lapatinib plus capecitabine is currently the best established systemic therapy option. Still, T-DM1 apparently offers relevant clinical activity in BM and further investigation is warranted. PMID:26303828

  4. Phase I Trial of Simultaneous In-Field Boost With Helical Tomotherapy for Patients With One to Three Brain Metastases

    SciTech Connect

    Rodrigues, George; Yartsev, Slav; Yaremko, Brian; Perera, Francisco; Dar, A. Rashid; Hammond, Alex; Lock, Michael; Yu, Edward; Ash, Robert; Caudrelier, Jean-Michelle; Khuntia, Deepak; Bailey, Laura; Bauman, Glenn

    2011-07-15

    Purpose: Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present study's objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT. Methods and Materials: The inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lower dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort. Results: A total of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients. Conclusion: The delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.

  5. Microenvironmental acidosis in carcinogenesis and metastases: new strategies in prevention and therapy.

    PubMed

    Fais, Stefano; Venturi, Giulietta; Gatenby, Bob

    2014-12-01

    Much effort is currently devoted to developing patient-specific cancer therapy based on molecular characterization of tumors. In particular, this approach seeks to identify driver mutations that can be blocked through small molecular inhibitors. However, this approach is limited by extensive intratumoral genetic heterogeneity, and, not surprisingly, even dramatic initial responses are typically of limited duration as resistant tumor clones rapidly emerge and proliferate. We propose an alternative approach based on observations that while tumor evolution produces genetic divergence, it is also associated with striking phenotypic convergence that loosely correspond to the well-known cancer "hallmarks". These convergent properties can be described as driver phenotypes and may be more consistently and robustly expressed than genetic targets. To this purpose, it is necessary to identify strategies that are critical for cancer progression and metastases, and it is likely that these driver phenotypes will be closely related to cancer "hallmarks". It appears that an antiacidic approach, by targetting a driver phenotype in tumors, may be thought as a future strategy against tumors in either preventing the occurrence of cancer or treating tumor patients with multiple aims, including the improvement of efficacy of existing therapies, possibly reducing their systemic side effects, and controlling tumor growth, progression, and metastasis. This may be achieved with existing molecules such as proton pump inhibitors (PPIs) and buffers such as sodium bicarbonate, citrate, or TRIS. PMID:25376898

  6. Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival

    SciTech Connect

    Stea, Baldassarre . E-mail: bstea@azcc.arizona.edu; Suh, John H.; Boyd, Adam P. M.S.; Cagnoni, Pablo J.; Shaw, Edward

    2006-03-15

    Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases. Methods and Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months. Results: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival. Conclusions: The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm.

  7. [A clinical case of combined treatment of a patient with breast cancer and metastases to the brain and meninges].

    PubMed

    Moskvina, E A; Naskhletashvili, D R; Bekyashev, A Kh; Medvedev, S V; Belov, D M; Gasparyan, T G

    2016-01-01

    The article describes a clinical case of successful chemotherapeutic and radiation treatment of a patient with breast cancer and metastases to the brain and meninges and with a pronounced neurological deficit. The patient underwent combined treatment (whole brain radiation with TBD of 30 Gy and local radiation of a metastasis with TBD of 15 Gy associated with capecitabine therapy) with continued administration of capecitabine until improvement. A partial metastasis reduction by 50% and complete regression of the neurological deficit were observed. Disease-free period was 1 year and 10 months, and the overall survival amounted to 2 years. PMID:27029334

  8. A Simple and Efficient Methodology To Improve Geometric Accuracy in Gamma Knife Radiation Surgery: Implementation in Multiple Brain Metastases

    SciTech Connect

    Karaiskos, Pantelis; Moutsatsos, Argyris; Pappas, Eleftherios; Georgiou, Evangelos; Roussakis, Arkadios; Torrens, Michael; Seimenis, Ioannis

    2014-12-01

    Purpose: To propose, verify, and implement a simple and efficient methodology for the improvement of total geometric accuracy in multiple brain metastases gamma knife (GK) radiation surgery. Methods and Materials: The proposed methodology exploits the directional dependence of magnetic resonance imaging (MRI)-related spatial distortions stemming from background field inhomogeneities, also known as sequence-dependent distortions, with respect to the read-gradient polarity during MRI acquisition. First, an extra MRI pulse sequence is acquired with the same imaging parameters as those used for routine patient imaging, aside from a reversal in the read-gradient polarity. Then, “average” image data are compounded from data acquired from the 2 MRI sequences and are used for treatment planning purposes. The method was applied and verified in a polymer gel phantom irradiated with multiple shots in an extended region of the GK stereotactic space. Its clinical impact in dose delivery accuracy was assessed in 15 patients with a total of 96 relatively small (<2 cm) metastases treated with GK radiation surgery. Results: Phantom study results showed that use of average MR images eliminates the effect of sequence-dependent distortions, leading to a total spatial uncertainty of less than 0.3 mm, attributed mainly to gradient nonlinearities. In brain metastases patients, non-eliminated sequence-dependent distortions lead to target localization uncertainties of up to 1.3 mm (mean: 0.51 ± 0.37 mm) with respect to the corresponding target locations in the “average” MRI series. Due to these uncertainties, a considerable underdosage (5%-32% of the prescription dose) was found in 33% of the studied targets. Conclusions: The proposed methodology is simple and straightforward in its implementation. Regarding multiple brain metastases applications, the suggested approach may substantially improve total GK dose delivery accuracy in smaller, outlying targets.

  9. Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

    SciTech Connect

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

    2012-10-01

    Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests. Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients. Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.

  10. Early Significant Tumor Volume Reduction After Radiosurgery in Brain Metastases From Renal Cell Carcinoma Results in Long-Term Survival

    SciTech Connect

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

    2012-04-01

    Purpose: To retrospectively evaluate survival of patients with brain metastasis from renal cell carcinoma (RCC) after radiosurgery. Patients and Methods: Between 1998 and 2010, 46 patients were treated with radiosurgery, and the total number of lesions was 99. The mean age was 58.9 years (range, 33-78 years). Twenty-six patients (56.5%) had a single brain metastasis. The mean tumor volume was 3.0 cm{sup 3} (range, 0.01-35.1 cm{sup 3}), and the mean marginal dose prescribed was 20.8 Gy (range, 12-25 Gy) at the 50% isodose line. A patient was classified into the good-response group when the sum of the volume of the brain metastases decreased to less than 75% of the original volume at a 1-month follow-up evaluation using MRI. Results: As of December 28, 2010, 39 patients (84.8%) had died, and 7 (15.2%) survived. The overall median survival time was 10.0 {+-} 0.4 months (95% confidence interval, 9.1-10.8). After treatment, local tumor control was achieved in 72 (84.7%) of the 85 tumors assessed using MRI after radiosurgery. The good-response group survived significantly longer than the poor-response group (median survival times of 18.0 and 9.0 months, respectively; p = 0.025). In a multivariate analysis, classification in the good-response group was the only independent prognostic factor for longer survival (p = 0.037; hazard ratio = 0.447; 95% confidence interval, 0.209-0.953). Conclusions: Radiosurgery seems to be an effective treatment modality for patients with brain metastases from RCC. The early significant tumor volume reduction observed after radiosurgery seems to result in long-term survival in RCC patients with brain metastases.

  11. Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases

    PubMed Central

    Lee, Seung Heon; Choi, Jinho; Kim, Hye Young; Lee, Seok Ho; Sung, Ki Hoon; Kim, Yunmi

    2012-01-01

    Purpose To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Materials and Methods Nine patients with multiple (≥4) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10-12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. Results The median biologically effective dose to metastatic tumors was 68.1 Gy10 and 67.2 Gy10 and the median brain volume irradiated more than 100 Gy3 were 1.9% (24 cm3) and 0.8% (13 cm3) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. Conclusion RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application. PMID:22984683

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

    SciTech Connect

    Likhacheva, Anna; Pinnix, Chelsea C.; Parikh, Neil R.; Allen, Pamela K.; McAleer, Mary F.; Chiu, Max S.; Sulman, Erik P.; Mahajan, Anita; Guha-Thakurta, Nandita; Prabhu, Sujit S.; Cahill, Daniel P.; Luo, Dershan; Shiu, Almon S.; Brown, Paul D.; Chang, Eric L.

    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.

  13. A Rare Cause of Bowel Obstruction: Peritoneal Metastases in Osteosarcoma at the Tibia in a Young Female Patient with Brain Metastasis. Case Report.

    PubMed

    Badiu, Dumitru Cristinel; Manea, Cristina Alexandra; Porojan, Vlad; Paraschiv, Marius; Mehedintu, Claudia; Coman, Ionut Simion; Grigorean, Valentin Titus

    2016-01-01

    Osteosarcomas are the most frequent primary malignant bone tumors in children and adolescents. Like brain metastases in osteosarcomas, the bowel metastases are very rare. We present the case of a 23-year-old female patient, diagnosed and operated in 2008 of osteosarcoma at the tibia, for which she had sessions of neoadjuvant and adjuvant chemotherapy, but presented lungs metastases for which she underwent surgery in 2014. Then, in March 2015, she was diagnosed with an intracranial expansive process, an osteosarcoma metastasis, for which a total ablation of the tumor was performed during the early postoperatory period, being transferred to the General Surgery Clinic for abdominal pain, abdominal distention, vomiting, and lack of intestinal transit regarding faeces and intestinal gas. Both clinically and imagistically, the diagnosis was of bowel obstruction. This was the reason for performing surgery, thus discovering a bowel obstruction secondary to a metastasis of the terminal ileum and liver metastases that were confirmed as osteosarcoma metastases from an anatomopathological and immunohistochemical point of view. The bowel metastases and the osteosarcoma brain metastases are very rare entities and, their association, most often with young patients, is exceptional. However, bowel metastases must be taken into account as a possible cause of bowel obstruction in patients with osteosarcoma. PMID:27452942

  14. Malignant potential of cells isolated from lymph node or brain metastases of melanoma patients and implications for prognosis.

    PubMed

    Zhang, R D; Price, J E; Schackert, G; Itoh, K; Fidler, I J

    1991-04-15

    We studied the correlation between the formation of brain metastasis and the malignant growth potential of seven human melanoma cell lines, isolated from lymph node metastases (A375-SM, TXM-1, DM-4) or from brain metastases (TXM-13, TXM-18, TXM-34, TXM-40), and the potential of three variants of the mouse K-1735 melanoma. Growth rates in different concentrations of fetal bovine serum and colony-forming efficiency in semisolid agarose were measured, and the tumorigenicity and metastatic ability were determined in nude mice (for the human melanoma cell lines) or in C3H/HeN mice (for the K-1735 variants). The ability to form brain metastasis was tested by injection of cells into the carotid artery. A high colony-forming efficiency in agarose, especially at concentrations of agarose greater than 0.6%, corresponded with high tumor take rates, rapid tumor growth rates, and metastatic colonization of the lungs of the recipient mice. For the human melanomas, the lymph node metastasis-derived cells were more tumorigenic and metastatic than the brain metastasis-derived cells. In the K-1735 mouse melanoma, the tumorigenic and metastatic behavior of the cells after i.v. and s.c. injection corresponded with growth in agarose cultures. However, for growth in the brain after intracarotid injection, the different melanoma cell lines showed similar frequencies of tumor take, regardless of tumorigenicity in other sites of the recipient mice, although mice given injections of brain metastasis-derived cells survived longer than mice given injections of lymph node metastasis (human melanoma) or lung metastasis (K-1735 M-2)-derived cell lines. The results from the human and mouse melanoma cell lines show that the brain metastasis-derived cell lines were not more malignant than the lymph node or lung metastasis-derived cells. These data imply that the production of brain metastasis is not always the final stage of a metastatic cascade. PMID:1826230

  15. Incidence of Brain Atrophy and Decline in Mini-Mental State Examination Score After Whole-Brain Radiotherapy in Patients With Brain Metastases: A Prospective Study

    SciTech Connect

    Shibamoto, Yuta Baba, Fumiya; Oda, Kyota; Hayashi, Shinya; Kokubo, Masaki; Ishihara, Shun-Ichi; Itoh, Yoshiyuki; Ogino, Hiroyuki; Koizumi, Masahiko

    2008-11-15

    Purpose: To determine the incidence of brain atrophy and dementia after whole-brain radiotherapy (WBRT) in patients with brain metastases not undergoing surgery. Methods and Materials: Eligible patients underwent WBRT to 40 Gy in 20 fractions with or without a 10-Gy boost. Brain magnetic resonance imaging or computed tomography and Mini-Mental State Examination (MMSE) were performed before and soon after radiotherapy, every 3 months for 18 months, and every 6 months thereafter. Brain atrophy was evaluated by change in cerebrospinal fluid-cranial ratio (CCR), and the atrophy index was defined as postradiation CCR divided by preradiation CCR. Results: Of 101 patients (median age, 62 years) entering the study, 92 completed WBRT, and 45, 25, and 10 patients were assessable at 6, 12, and 18 months, respectively. Mean atrophy index was 1.24 {+-} 0.39 (SD) at 6 months and 1.32 {+-} 0.40 at 12 months, and 18% and 28% of the patients had an increase in the atrophy index by 30% or greater, respectively. No apparent decrease in mean MMSE score was observed after WBRT. Individually, MMSE scores decreased by four or more points in 11% at 6 months, 12% at 12 months, and 0% at 18 months. However, about half the decrease in MMSE scores was associated with a decrease in performance status caused by systemic disease progression. Conclusions: Brain atrophy developed in up to 30% of patients, but it was not necessarily accompanied by MMSE score decrease. Dementia after WBRT unaccompanied by tumor recurrence was infrequent.

  16. [The case of a long-surviving patient with breast cancer and brain metastases treated using multidisciplinary therapy].

    PubMed

    Nishimura, Akimasa; Nishi, Takashi; Morohashi, Satoko; Okano, Kensuke; Hakamada, Kenichi

    2014-11-01

    We present the case of a 55-year-old-woman who was diagnosed with left breast cancer, and underwent a left mastectomy and left axillary lymph node resection. The histopathological examination indicated scirrhous carcinoma and lesser papillotubular carcinoma[estrogen receptor-negative (ER-), progesterone receptor-negative(PgR-), and human epidermal growth factor receptor 2-positive, grade 3 (HER2, 3+)] with lymph node metastases. Adjuvant chemotherapy consisting of epirubicin and cyclophosphamide (EC) followed by paclitaxel was administered. During the therapy, the patient noticed a mass on her left chest wall. It was diagnosed as a locally recurrent tumor. A computed tomography (CT) scan indicated supraclavicular lymph node metastasis. The patient underwent radiotherapy and was administered chemotherapy with TS-1 and trastuzumab. Brain metastases were found 24 months postoperatively, and the patient underwent surgery and wholebrain radiotherapy. After these, systemic capecitabine and trastuzumab chemotherapy was administered. The therapy was subsequently changed to capecitabine and lapatinib. There have been no subsequent metastatic tumors, and good control has been achieved for a long time after the detection of brain metastases. PMID:25731368

  17. Prognostic Value of MR Imaging Texture Analysis in Brain Non-Small Cell Lung Cancer Oligo-Metastases Undergoing Stereotactic Irradiation

    PubMed Central

    Tini, Paolo; Biondi, Michelangelo; Sebaste, Lucio; Vanzi, Eleonora; De Otto, Gianmarco; Rubino, Giovanni; Carfagno, Tommaso; Battaglia, Giuseppe; Pastina, Pierpaolo; Cerase, Alfonso; Mazzoni, Lorenzo Nicola; Banci Buonamici, Fabrizio; Pirtoli, Luigi

    2016-01-01

    Background  Stereotactic irradiation is widely used in brain oligo-metastases treatment. The aim of this study is to evaluate the prognostic value of magnetic resonance imaging (MRI) texture analysis (TA) of brain metastases (BM) of non-small cell lung cancer (NSCLC). Materials and methods  This study included thirty-eight consecutive patients undergoing stereotactic irradiation, that is, stereotactic fractionated radiotherapy (SRT) or radiosurgery (SRS), from January 2011 to December 2014 for 1-2 brain BM from NSCLC. Whole-brain radiotherapy (WBRT) was not delivered. The diagnostic MRI DICOM (Digital Imaging and Communications in Medicine) images were collected and analyzed with a homemade ImageJ macro, and typical TA parameters (mean, standard deviation, skewness, kurtosis, entropy, and uniformity) were evaluated for: brain progression-free survival; modality of brain metastatic progression (local progression or/and new metastases); and overall survival, after SRT/SRS. Results After SRT/SRS 14 patients (36.8%) experienced recurrence in the brain, with a recurrence in the irradiated site (five patients, 13.2%), new metastases (11 patients, 28.9%), local recurrence and new metastases (two patients, 5.25%). Nineteen patients (50%) died of tumor progression or other causes. Entropy and uniformity were significantly associated with local progression, whereas kurtosis was significantly associated with both local progression and new brain metastases. Conclusions  These results appear promising, since the knowledge of factors correlated with the modality of brain progression after stereotactic irradiation of brain oligo-metastatic foci of NSCLC might help in driving the best treatment in these patients (association of SRT/SRS with WBRT? Increase of SRT/SRS dose?). Our preliminary data needs confirmation in large patient series. PMID:27226944

  18. Ultrasound Imaging-guided Intracardiac Injection to Develop a Mouse Model of Breast Cancer Brain Metastases Followed by Longitudinal MRI

    PubMed Central

    Zhou, Heling; Zhao, Dawen

    2014-01-01

    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. PMID:24637963

  19. Clinical and molecular characteristics of HNSCC patients with brain metastases: a retrospective study.

    PubMed

    Bulut, Olcay Cem; Lindel, Katja; Hauswald, Henrik; Brandt, Regine; Klauschen, Frederick; Wolf, Janina; Wolf, Thomas; Plinkert, Peter K; Simon, Christian; Weichert, Wilko; Stenzinger, Albrecht

    2014-06-01

    Among the metastasis patterns of head and neck squamous cell carcinoma (HNSCC), intracranial spread is a rare but dreaded event. To date only very few cases have been reported and clinical and molecular data are sparse. We screened our archives for HNSCC patients from 1992 to 2005 who were diagnosed with brain metastases (BM). For retrospective analysis, all clinico-pathological data including disease-free survival (DFS), local progression-free survival (LPFS), and overall survival (OS) were compiled. Additionally, we assessed the mutational status of the TP53 gene and the prevalence of HPV serotypes by PCR and Sanger sequencing. Immunohistochemistry was applied to detect p16INK4A expression levels as surrogate marker for HPV infection. The prevalence rate of BM in our cohort comprising 193 patients with advanced HNSCC was 5.7%. Of 11 patients with BM, 3 were female and 9 were male. Seven of the primary tumors were of oropharyngeal origin (OPSCC). LPFS of the cohort was 11.8 months, DFS was 12.1 months and OS was 36.0 months. After the diagnosis of BM, survival was 10.5 months. Five tumors showed a mutation in the TP53 gene, while five of the seven OPSCC tumors had a positive HPV status displaying infection with serotype 16 in all cases. Compared with patients who harbored TP53wt/HPV-positive tumors, patients with TP53 mutations showed a poor prognosis. Compared with the whole cohort, the interval between diagnosis of the primary and the detection of BM was prolonged in the HPV-infected OPSCC subgroup (26.4 vs. 45.6 months). The prognosis of HNSCC patients with BM is poor. In our cohort, most tumors were OPSCC with the majority being HPV positive. Our study points toward a putatively unusual metastatic behavior of HPV-positive OPSCC. PMID:23990032

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

    SciTech Connect

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

    2012-04-01

    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.

  1. Gamma Knife radiosurgery combined with stereotactic aspiration as an effective treatment method for large cystic brain metastases

    PubMed Central

    WANG, HONGWEI; QI, SONGTAO; DOU, CHANGWU; JU, HAITAO; HE, ZHANBIAO; MA, QINGHAI

    2016-01-01

    In the present study, the efficacy and clinical outcomes of stereotactic aspiration combined with the Gamma Knife radiosurgery (GKRS) method were evaluated retrospectively for patients with large cystic brain metastases. This combined method aims to decrease the tumor weight (volume) and increase the possible radiation dose. The present study involved 48 patients who were diagnosed with cystic metastatic brain tumors between January 2008 and December 2012 in the Department of Neurosurgery of Nanfang Hospital Southern Medical University (Guangzhou, China). Every patient underwent Leksell stereotactic frame, 1.5T magnetic resonance imaging (MRI)-guided stereotactic cyst aspiration and Leksell GKRS. Subsequent to the therapy, MRI was performed every 3 months. The results indicated that 48 cases were followed up for 24–72 months, with a mean follow-up duration of 36.2 months. Following treatment, 44 patients (91.7%) exhibited tumor control and 4 patients (8.3%) experienced progression of the local tumor. During this period, 35 patients (72.9%) succumbed, but only 2 (4.2%) of these succumbed to the brain metastases. The total local control rate was 91.7% and the median overall survival time of all patients was 19.5 months. The 1-year overall survival rate was 70.8% and the 2-year overall survival rate was 26.2%. In conclusion, these results indicated that the method of stereotactic cyst aspiration combined with GKRS was safe and effective for patients with large cystic brain metastases. This method is effective for patients whose condition is too weak for general anesthesia and in whom the tumors are positioned at eloquent areas. This method enables patients to avoid a craniotomy, and provides a good tumor control rate, survival time and quality of life. PMID:27347148

  2. Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases

    PubMed Central

    Harter, Patrick N.; Bernatz, Simon; Scholz, Alexander; Zeiner, Pia S.; Zinke, Jenny; Kiyose, Makoto; Blasel, Stella; Beschorner, Rudi; Senft, Christian; Bender, Benjamin; Ronellenfitsch, Michael W.; Wikman, Harriet; Glatzel, Markus; Meinhardt, Matthias; Juratli, Tareq A.; Steinbach, Joachim P.; Plate, Karl H.; Wischhusen, Jörg; Weide, Benjamin; Mittelbronn, Michel

    2015-01-01

    The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts. PMID:26517811

  3. Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance.

    PubMed

    Saunus, Jodi M; Quinn, Michael C J; Patch, Ann-Marie; Pearson, John V; Bailey, Peter J; Nones, Katia; McCart Reed, Amy E; Miller, David; Wilson, Peter J; Al-Ejeh, Fares; Mariasegaram, Mythily; Lau, Queenie; Withers, Teresa; Jeffree, Rosalind L; Reid, Lynne E; Da Silva, Leonard; Matsika, Admire; Niland, Colleen M; Cummings, Margaret C; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Kassahn, Karin S; Narayanan, Vairavan; Taib, Nur Aishah; Teo, Soo-Hwang; Chow, Yock Ping; kConFab; Jat, Parmjit S; Brandner, Sebastian; Flanagan, Adrienne M; Khanna, Kum Kum; Chenevix-Trench, Georgia; Grimmond, Sean M; Simpson, Peter T; Waddell, Nicola; Lakhani, Sunil R

    2015-11-01

    Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2)  = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting

  4. Prevention of nodal metastases in breast cancer following the lymphatic migration of paclitaxel-loaded expansile nanoparticles

    PubMed Central

    Liu, Rong; Gilmore, Denis M.; Zubris, Kimberly Ann V.; Xu, Xiaoyin; Catalano, Paul J.; Padera, Robert F.; Grinstaff, Mark W.; Colson, Yolonda L.

    2012-01-01

    Although breast cancer patients with localized disease exhibit an excellent long-term prognosis, up to 40% of patients treated with local resection alone may harbor occult nodal metastatic disease leading to increased locoregional recurrence and decreased survival. Given the potential for targeted drug delivery to result in more efficacious locoregional control with less morbidity, the current study assessed the ability of drug-loaded polymeric expansile nanoparticles (eNP) to migrate from the site of tumor to regional lymph nodes, locally deliver a chemotherapeutic payload, and prevent primary tumor growth as well as lymph node metastases. Expansile nanoparticles entered tumor cells and paclitaxel-loaded eNP (Pax-eNP) exhibited dose-dependent cytotoxicity in vitro and significantly decreased tumor doubling time in vivo against human triple negative breast cancer in both microscopic and established murine breast cancer models. Furthermore, migration of Pax-eNP to axillary lymph nodes resulted in higher intranodal paclitaxel concentrations and a significantly lower incidence of lymph node metastases. These findings demonstrate that lymphatic migration of drug-loaded eNP provides regionally targeted delivery of chemotherapy to both decrease local tumor growth and strategically prevent the development of nodal metastases within the regional tumor-draining lymph node basin. PMID:23228419

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

    SciTech Connect

    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.

    2014-10-01

    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

  6. Phase 3 Trials of Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis

    SciTech Connect

    Sahgal, Arjun; Aoyama, Hidefumi; Kocher, Martin; Neupane, Binod; Collette, Sandra; Tago, Masao; Shaw, Prakesh; Beyene, Joseph; Chang, Eric L.

    2015-03-15

    Purpose: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRS alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group.

  7. [A Case of Brain Metastasis from Rectal Cancer with Synchronous Liver and Lung Metastases after Multimodality Treatment--A Case Report].

    PubMed

    Udagawa, Masaru; Tominaga, Ben; Kobayashi, Daisuke; Ishikawa, Yuuya; Watanabe, Shuuichi; Adikrisna, Rama; Okamoto, Hiroyuki; Yabata, Eiichi

    2015-11-01

    We report a case of brain metastasis from rectal cancer a long time after the initial resection. A 62-year-old woman, diagnosed with lower rectal cancer with multiple synchronous liver and lung metastases, underwent abdominoperineal resection after preoperative radiochemotherapy (40 Gy at the pelvis, using the de Gramont regimen FL therapy: 1 kur). The histological diagnosis was a moderately differentiated adenocarcinoma. Various regimens of chemotherapy for unresectable and metastatic colorectal cancer were administered, and a partial response was obtained; thereby, the metastatic lesions became resectable. The patient underwent partial resection of the liver and lung metastases. Pathological findings confirmed that both the liver and lung lesions were metastases from the rectal cancer. A disease-free period occurred for several months; however, there were recurrences of the lung metastases, so we started another round of chemotherapy. After 8 months, she complained of vertigo and dizziness. A left cerebellar tumor about 3 cm in diameter was revealed by MRI and neurosurgical excision was performed. Pathological findings confirmed a cerebellar metastasis from the rectal cancer. Twenty months after resection of the brain tumor, the patient complained of a severe headache. A brain MRI showed hydrocephalia, and carcinomatous meningitis from rectal cancer was diagnosed by a spinal fluid cytology test. A ventriculo-peritoneal shunt was inserted, but the cerebrospinal pressure did not decreased and she died 20 months after the first surgery. Although brain metastasis from colorectal cancer is rare, the number of patients with brain metastasis is thought to increase in the near future. Chemotherapy for colorectal cancer is effective enough to prolong the survival period even if multiple metastases have occurred. However, after a long survival period with lung metastases such as in our case, there is a high probability of developing brain metastases. PMID:26805112

  8. Brain metastases in Asian HER2-positive breast cancer patients: anti-HER2 treatments and their impact on survival

    PubMed Central

    Yap, Y S; Cornelio, G H; Devi, B C R; Khorprasert, C; Kim, S B; Kim, T Y; Lee, S C; Park, Y H; Sohn, J H; Sutandyo, N; Wong, D W Y; Kobayashi, M; Landis, S H; Yeoh, E M; Moon, H; Ro, J

    2012-01-01

    Background: In Asia, large-scale studies on anti-HER2 treatment in HER2-positive breast cancer patients with brain metastases are limited. We studied the treatment patterns of these patients in Asia to evaluate the impact of anti-HER2 treatment on the time to occurrence of brain metastases (TTBM) and survival after brain metastasis (BM). Methods: A retrospective study of HER2-positive breast cancer patients diagnosed with BM between January 2006 and December 2008 in six Asian countries was conducted. Demographics, tumour characteristics, treatment details, and events dates were collected from medical records. Results: Data from 280 patients were analysed. Before BM, 63% received anti-HER2 treatment. These patients had significantly longer TTBM than those without anti-HER2 treatment (median 33 vs 19 months; P<0.002). After BM, 93% received radiotherapy, 57% received chemotherapy, and 41% received anti-HER2 treatment (trastuzumab and/or lapatinib). Use of both anti-HER2 agents, primarily sequentially, after BM demonstrated the longest survival after BM and was associated with a significant survival benefit over no anti-HER2 treatment (median 26 vs 6 months; hazard ratio 0.37; 95% CI 0.19–0.72). Conclusion: Anti-HER2 treatment before BM was associated with longer TTBM. Anti-HER2 treatment after BM was associated with a survival benefit, especially when both trastuzumab and lapatinib were utilised. PMID:22918394

  9. A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

    SciTech Connect

    Knisely, Jonathan P.S. Berkey, Brian; Chakravarti, Arnab; Yung, Al W.K.; Curran, Walter J.; Robins, H. Ian; Movsas, Benjamin; Brachman, David G.; Henderson, Randall H.; Mehta, Minesh P.

    2008-05-01

    Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.

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

    SciTech Connect

    Sperduto, Paul W.; Kased, Norbert; Roberge, David; Xu Zhiyuan; Shanley, Ryan; Luo, Xianghua; Sneed, Penny K.; Chao, Samuel T.; Weil, Robert J.; Suh, John; Bhatt, Amit; Jensen, Ashley W.; Brown, Paul D.; Shih, Helen A.; Kirkpatrick, John; Gaspar, Laurie E.; Fiveash, John B.; 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.