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Brain Metastases (brain + metastase)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Oncology & Radiotherapy	54%
Neurology	7%
Pathology	4%
7 Other Subdomains	35%

Kinds of Brain Metastases

multiple brain metastase

Selected Abstracts

Headache characteristics and brain metastases prediction in cancer patients

EUROPEAN JOURNAL OF CANCER CARE, Issue 1 2006
A.A. ARGYRIOU md
The aim of this study was to evaluate the headache and other neurological symptoms and signs as guide predictors for the occurrence of brain metastases in cancer patients. We prospectively studied 54 cancer patients with newly appeared headache or with a change in the pattern of an existing headache during the recent months. All patients completed a questionnaire regarding headache's clinical characteristics and existence of accompanying symptoms. They also underwent a detailed neurological, ophthalmologic examination and brain neuroimaging investigation. Brain metastases were diagnosed in 29 patients. Univariate regression analysis showed an association between occurrence of brain metastases and nine clinical symptoms or signs. Multivariate regression analyses emerged only four of them as significant independent predictors. These were: bilateral frontal-temporal headache, more pronounced on the side of metastasis in cases of single metastases, with duration ,8 weeks, pulsating quality and moderate to severe intensity (OR: 11.9; 95% CI. 2.52,56.1), emesis (OR: 10.2; 95% CI. 2.1,55.8), gait instability (OR: 7.4; 95% CI. 1.75,33.9) and extensor plantar response (OR: 12.1; 95% CI. 2.2,120.7). In conclusion, all cancer patients who manifest the above independent clinical predictors should be highly suspected for appearance of brain metastases and therefore should be thoroughly investigated. [source]

Brain metastases from testicular germ cell tumors: A retrospective analysis

INTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2009
Norio Nonomura
Objectives: To review our series of testicular germ cell tumors with brain metastases and to establish an optimal treatment strategy for them. Methods: Twenty-seven cases of testicular germ cell tumors from three institutions were retrospectively reviewed. Results: Twenty-six were non-seminomatous tumors and only one was a seminoma. Based on the International Germ Cell Consensus Classification, two cases were classified as good prognosis, seven as intermediate prognosis and 18 as poor prognosis. Chemotherapy was carried out in all patients. Additionally, whole-brain radiotherapy was performed in 10 cases, stereotactic radiosurgery in six, whole-brain radiotherapy combined with stereotactic radiosurgery in three and complete surgical resection in five. Three patients received chemotherapy only. Cancer-specific 5- and 10-year survival rates were both 35.9%. The prognosis of those with brain metastases at the time of diagnosis tended to be better than those developing brain metastases during treatment. Those with a single brain metastasis showed significantly better survival than those with multiple brain metastases. No other significant prognostic factor was found at multivariate analysis. Conclusion: Testicular germ cell tumors with brain metastases can be managed with the combination of whole-brain radiotherapy, stereotactic radiotherapy, and/or surgical resection in combination with chemotherapy. [source]

Survival in patients with brain metastases from breast cancer

CANCER, Issue 11 2008
The importance of HER-2 status
Abstract BACKGROUND Brain metastases (BM) are the most common intracranial tumors in adults. To the authors' knowledge, established prognostic factors for survival after the diagnosis of BM in breast cancer patients do not take into account HER,2 status, which may have increasing relevance in the trastuzumab therapy era. METHODS The authors identified 83 patients with breast cancer and new parenchymal BM diagnosed between January 1, 2001 and December 31, 2005 who were treated at Massachusetts General Hospital. Survival was estimated using the Kaplan-Meier method and curves were compared using the log-rank test. A Cox proportional hazards model was used to determine independent predictors of survival. RESULTS The median overall survival from the time of BM was 8.3 months. On univariate analysis, HER-2-positive patients were found to have prolonged survival after BM compared with HER-2-negative patients (17.1 months vs 5.2 months). Patients with triple negative disease had a median survival of 4.0 months, compared with 11.2 months for all other patients. Additional predictors of improved survival on univariate analysis included ,3 BM, controlled or absent systemic disease, and controlled local disease. On multivariate analysis, only HER-2 status, number of BM, and local disease status remained independent predictors of survival. CONCLUSIONS HER-2 status is a strong predictor of survival after the diagnosis of BM. The survival of breast cancer patients with BM appears to be improving, but a better understanding of both the predictors of brain recurrence and the delayed effects of treatment is needed to properly counsel patients regarding the risk-benefit ratio of various treatment modalities. Cancer 2008. © 2008 American Cancer Society. [source]

Neurologic disorders in 432 consecutive patients with small cell lung carcinoma

CANCER, Issue 4 2004
Tatjana Seute M.D.
Abstract BACKGROUND Neurologic complications are an important cause of morbidity and possibly also mortality in patients with small cell lung carcinoma (SCLC). The current study was undertaken to prospectively investigate survival and the frequency of neurologic disorders in patients with SCLC. METHODS Between October 1980 and September 2001, 432 consecutive patients with microscopically proven SCLC were included in the current study. Patients underwent neurologic examinations on a regular basis prior to, during, and after treatment. Routine imaging of the brain (computed tomography or magnetic resonance imaging) was performed before and after systemic therapy. RESULTS A neurologic disorder was diagnosed in approximately 56% of the SCLC patients. In nearly half of the cases, the neurologic disorder already was present at the time of diagnosis. Brain metastases (BM) were diagnosed most frequently. Seventy-four patients (18%) had BM at the time of diagnosis; in 20 of these patients, the BM did not demonstrate clinical signs. Another 101 patients developed BM during follow-up. The 2-year cumulative risk of BM reached 49% for patients with limited disease (LD) and 65% for patients with extensive disease (ED). Patients with BM as the only site of disease dissemination were found to have a poorer survival compared with LD patients. The majority of the nonmetastatic disorders preceded the diagnosis of SCLC. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was diagnosed most frequently. CONCLUSIONS In this prospective study, neurologic disorders were diagnosed in greater than half of the patients with SCLC. BM were detected most frequently. Approximately 18% of the patients were found to have BM at the time of diagnosis. In approximately 33% of the cases, these BM did not cause symptoms. BM were found to have a negative effect on survival in patients with SCLC. Cancer 2004;100:801,6. © 2004 American Cancer Society. [source]

Brain metastases in locally advanced nonsmall cell lung carcinoma after multimodality treatment

CANCER, Issue 3 2002
Risk factors analysis
Abstract BACKGROUND Brain metastases (BM) are frequent sites of initial failure in patients with locally advanced nonsmall cell lung cancer (LAD-NSCLC) undergoing multimodality treatments (MMT). New treatment and follow-up strategies are needed to reduce the risk of BM and to diagnose them early enough for effective treatment. METHODS The incidence rate of BM as the first site of recurrence in 112 patients with LAD-NSCLC treated with the same MMT protocol was calculated. The influence of patient, disease, and treatment-related factors on the incidence of BM and on the time-to-brain recurrence (TBR) was analyzed. RESULTS BM as the first site of failure was observed in 25 cases (22% of the study population and 29% of all recurrences). In 18 of those cases, the brain was the exclusive site of recurrence. Median TBR was 9 months. The 2-year actuarial incidence of BM was 29%. Central nervous system (CNS) recurrence was more common in patients younger than 60 years (P = 0.006) and in whom bulky (, 2 cm) mediastinal lymph nodes were present (P = 0.02). TBR was influenced by age (P = 0.004) and by bulky lymph node disease (P = 0.003). Multivariate analysis confirmed the prognostic role of age, whereas the presence of clinical bulky mediastinal lymph nodes was of borderline significance. CONCLUSIONS Our study confirmed a high rate of BM in patients with LAD-NSCLC submitted to MMT. Most of these CNS recurrences were isolated and occurred within 2 years of initial diagnosis. Age younger than 60 years was associated with an increased risk of BM and reduced TBR, whereas the presence of clinical bulky mediastinal lymph nodes was of borderline significance. Although our data require further validation in future studies, our results suggest that additional trials on prophylactic cranial irradiation and on intensive radiologic follow-up should focus on these high-risk populations. Cancer 2002;95:605,12. © 2002 American Cancer Society. DOI 10.1002/cncr.10687 [source]

Peduncular hallucinosis due to brain metastases from cervix cancer: a case report

ACTA NEUROPSYCHIATRICA, Issue 3 2003
Mustafa Gokce
Background:, Brain metastases from cervical carcinoma are rare. Accompanying symptoms depend on the location of the metastatic lesions. Penduncular hallucinosis is a vivid form of hallucination with clinical findings indicating a lesion of the upper midbrain. We hereby report a probable first case of peduncular hallucinosis associated with brain metastases from cervical cancer. Case:, A 42-year-old woman had been diagnosed with adenocarcinoma of cervix. On admission for her increasing pelvic pain, she had complex visual hallucinations comprising cartoon children, figurative people and a foggy room. Magnetic resonance imaging of the head revealed a lesion in the left mesencephalothalamic area. Conclusion:, Peduncular hallucinosis is well known for its vivid and life-like characteristics associated with a mesencephalic area lesion, and recognition of this may be useful of its diagnosis and differential diagnosis from confusion and other hallucinations. [source]

Aspiration biopsy cytomorphology of primary pulmonary germ cell tumor metastatic to the brain

DIAGNOSTIC CYTOPATHOLOGY, Issue 10 2009
Haitham Arabi M.D.
Abstract Extragonadal germ cell tumors are uncommon and such tumors originating from the lung parenchyma are extremely rare. This is a case of 68-year-old female who was admitted with complaints of right-sided weakness, inability to maintain her balance, right-sided headache, and bloody sputum. Her workup revealed two enhancing brain lesions and large lung mass involving the left lower lobe. Fine-needle aspiration (FNA) of the lung followed by craniotomy was performed and the patient was initially diagnosed with lung adenocarcinoma metastatic to the brain based on the cytomorphology of the lung FNA and histology of the brain mass. However, retrospective investigation revealed markedly elevated alpha fetoprotein (AFP) of which the cytopathologist was unaware at the time of diagnosis. A review of the cytology and surgical specimen slides, as well as immunohistochemistry (IHC) on the brain tumor and FNA cell block were preformed. On the basis of the slides review, clinical findings, and immunostaining results, a diagnosis of primary pulmonary mixed germ cell tumor, containing choriocarcinoma and yolk sac elements, with brain metastases, was retrospectively made. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source]

Headache characteristics and brain metastases prediction in cancer patients

Role of endoscopic surgery in the management of selected malignant epithelial neoplasms of the naso-ethmoidal complex

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2007
Piero Nicolai MD
Abstract Background. This study reviews the outcome of patients with adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the naso-ethmoidal complex treated by endoscopic surgery. Methods. Sixteen patients underwent a purely endoscopic excision of AC (n = 12) or SCC (n = 4) at 2 university hospitals. All patients were prospectively followed by endoscopic and MRI evaluations. Results. The tumor originated from the ethmoid in 13 cases and the nasal fossa in 3. Lesions were staged as follows: 5 T1, 10 T2, and 1 T3. Adjuvant radiotherapy was delivered in 7 cases. Follow-up (range, 28,70 months; mean, 47.25) was available for all patients. One patient died for brain metastases 28 months after surgery. Another patient required salvage craniofacial resection and radiotherapy for recurrent AC. Five-year disease-specific and disease-free survival rates were 93.3% and 87.0%, respectively. Conclusions. In selected T1-T2 lesions of the naso-ethmoidal complex, endoscopic surgery seems to offer a satisfactory alternative to external procedures. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source]

Renal cell carcinoma marker reliably discriminates central nervous system haemangioblastoma from brain metastases of renal cell carcinoma

HISTOPATHOLOGY, Issue 6 2008
B Ingold
Aims:, The distinction between central nervous system (CNS) metastases of clear cell renal cell carcinoma (RCC) and CNS haemangioblastoma still poses a challenge to the pathologist. Since both entities occur in von Hippel,Lindau disease, this aggravates the issue. The antibody renal cell carcinoma marker (RCC-ma) has been suggested to identify primary RCCs specifically, but its value for diagnosing metastases of RCC is controversial. The aim was to assess two distinct clones of the RCC-ma for their potential to: (i) identify primary RCCs and (ii) differentiate between CNS metastases of clear cell RCC and CNS haemangioblastomas. Methods and results:, Using tissue microarrays, 77% (n = 363; PN-15) and 66% (n = 355; 66.4C2) of clear cell RCCs, and 93% (PN-15) and 74% (66.4C2) of papillary RCCs (n = 46) were immunopositive for RCC-ma, whereas none of the investigated chromophobe RCCs (n = 22) or any of the oncocytomas (n = 15) showed immunoreactivity. Importantly, 50.9% of CNS metastases of clear cell RCCs (n = 55) exhibited RCC-ma expression, whereas all CNS haemangioblastomas (71) were negative. Conclusions:, Both RCC-ma clones, despite some variation in their sensitivity to detect clear cell and papillary RCCs, are of value in differentiating subtypes of primary RCC and are excellent markers for discriminating clear cell lesions in the brain. [source]

Management of brain metastases

INTERNAL MEDICINE JOURNAL, Issue 5 2004
L. C. Lim
Abstract Solid tumour brain metastases are a frequent clinical dilemma for oncologists and general physicians. The sound management of brain metastases requires a multidisciplinary approach. In this review we discuss the diagnosis and management of brain metastases including the role of surgery, radiotherapy, and chemotherapy. The standard approaches of surgical excision and primary radiotherapy have evolved from randomised studies. However, controversies remain regarding post-surgery irradiation in the setting of a solitary metastasis and the role of palliative chemotherapy. (Intern Med J 2004; 34: 270,278) [source]

Brain metastases from testicular germ cell tumors: A retrospective analysis

Primary Pulmonary Artery Sarcoma: Surgical Management and Differential Diagnosis with Pulmonary Embolism and Pulmonary Valve Stenosis

JOURNAL OF CARDIAC SURGERY, Issue 6 2009
Xiao-Peng Hu M.D.
We present six cases of primary pulmonary artery sarcomas and discuss clinical features, differential diagnosis, surgical treatment, and outcome of the tumors. Methods: Between January 1994 and July 2008, six patients were identified with the disease during operation. Three patients were initially diagnosed with pulmonary valve stenosis, and two patients had a presumptive diagnosis of chronic pulmonary embolism. Two patients had simple or partial tumor resection. Four patients had radical tumor resection and homograft reconstruction of the pulmonary arteries. Results: Histological examinations showed five malignant mesenchymomas and one fibrosarcoma. One patient died of refractory pulmonary hypertension during operation. Two patients died 4 months postoperatively because of brain metastases. Two patients were alive for 3 and 9 months, respectively after the operation with recurrent tumor. One patient is alive even 2 years after resection with no signs of recurrence or metastasis. Conclusions: Because of similar clinical features, pulmonary artery sarcomas are often confused with other pulmonary vascular obstructive diseases. Computed tomography scanning and gadolinium-enhanced magnetic resonance imaging could be useful methods for differential diagnosis. The prognosis is very poor. The survival time after resection varies from several months to several years depending on the presence of recurrence or metastasis. Early diagnosis and radical surgical resection presents the only opportunity for a potential cure. [source]

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

JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 1 2010
P Sundaresan
Summary Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks (,early death') may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of ,early death'. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with ,early death'. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of ,early death'. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for ,early death'. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool. [source]

Pulmonary myoepithelial carcinoma resembling matrix-producing carcinoma of the breast: case report and review of the literature

APMIS, Issue 5 2010
JIN TANAHASHI
Tanahashi J, Kashima K, Daa T, Yada N, Tanaka K-I, Kawano Y, Yokoyama S. Pulmonary myoepithelial carcinoma resembling matrix-producing carcinoma of the breast: case report and review of the literature. APMIS 2010; 118: 401,6. We report a case of pulmonary myoepithelial carcinoma with extensive myxohyaline stroma, resembling matrix-producing carcinoma of the breast. A 76-year-old Japanese man presented with a nodular lesion in the left lung (S8), and underwent partial resection of the left lower lobe. Microscopically, the resected tumor was relatively well circumscribed with central hypocellular myxohyaline and peripheral hypercellular area. In the central area, eosinophilic and clear polygonal cells proliferated in a cord-like or reticulated pattern with extensive myxohyaline stroma, while the peripheral area was composed of solid lobules of different shapes and sizes with occasional comedonecrosis. The tumor cells were markedly atypical with frequent mitotic figures. Vascular and lymphatic invasion was evident with regional lymph node metastasis. No squamous or glandular differentiation was evident in the tumor. Immunohistochemical staining implied myoepithelial differentiation. The patient developed multiple brain metastases, and died of the disease 11 months after the surgery. In this report, we discuss the histopathologic uniqueness of the present case together with a review of the literature. [source]

Clinical recommendations for the use of lapatinib ditosylate plus capecitabine for patients with advanced or metastatic HER2-positive breast cancer

ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2009
Raymond D SNYDER
Abstract Primary and acquired resistance to trastuzumab pose a therapeutic challenge when treating patients with HER2 (erbB-2)-positive locally advanced or metastatic breast cancer (MBC). The recent introduction of lapatinib (Tykerb/Tyverb, GlaxoSmithKline, Brentford, UK) provides a new management option for such patients. A prospective, randomized phase III clinical trial has confirmed that lapatinib in combination with capecitabine extends time to progressive disease in HER2-positive MBC, compared with capecitabine alone in patients with disease progression despite prior anthracycline, taxane and trastuzumab therapy. Preliminary data also indicate that lapatinib may exert a beneficial effect on brain metastases, a common sanctuary site for HER2-positive breast cancer following trastuzumab treatment. The tolerability of lapatinib is commensurate with that of other erbB family tyrosine kinase inhibitors and no significant new adverse events have emerged following its introduction into clinical practice. In particular, no additive cardiotoxicity has been observed when lapatinib is prescribed after trastuzumab therapy. Based on the published literature and supplemented by clinical experience, this article provides practical management recommendations for the use of lapatinib plus capecitabine in patients with MBC. Issues addressed include patient selection, baseline evaluation and monitoring for clinical benefit. The minimization and management of adverse events is also discussed in detail, particularly the dermatological and gastrointestinal effects, which are the most clinically significant side-effects of lapatinib therapy. Further recommendations cover the minimization of drug interactions, anticipated dosing alterations and the optimal employment of oral anticancer regimens. [source]

Intracranial tumor surgery in patients >70 years of age: is clinical practice worthwhile or futile?

ACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009
S. G. Rogne
Objectives,,, To study survival and functional outcome after intracranial tumor surgery in elderly patients. Materials and methods,,, This is a retrospective study of 289 consecutive patients of age ,70 years, who underwent primary surgery (resection or biopsy) in the time period 2003,2007 for an intracranial tumor (87 astrocytomas, 79 meningiomas, 62 brain metastases, 33 pituitary adenomas and 28 other tumors). Results,,, The surgical mortality was 2.8%. Overall survival at 6 months, 1, 2 and 5 years was 73%, 57%, 46% and 38% respectively. Histology, pre-operative Eastern Cooperative Oncology Group (ECOG) performance score and resection, as opposed to biopsy, were significantly associated with survival. Gender, age and American Association of Anaesthetists (ASA) score were not significantly related to survival. One-year survival after surgery for astrocytoma, meningioma, brain metastases and pituitary adenoma were 24%, 94%, 31% and 96% respectively. More than 85% of the patients who were alive 6 months after surgery had a stable or improved ECOG score compared with their pre-operative score. Conclusions,,, Surgery for intracranial tumors in selected elderly patients is worthwhile, not futile. Age alone should not be used as a selection criterion for treatment. [source]

Breast cancer subtypes and response to systemic treatment after whole-brain radiotherapy in patients with brain metastases

CANCER, Issue 18 2010
Anna Niwi, ska MD
Abstract BACKGROUND: The aim of this study was to assess the role of systemic treatment after whole-brain radiotherapy (WBRT) in immunohistochemically defined biological subsets of breast cancer patients with brain metastases. METHODS: The group of 420 consecutive breast cancer patients with brain metastases treated at the same institution between the years of 2003 to 2009 was analyzed. Patients were divided into 4 immunohistochemically biological subsets, based on the levels of estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptors, and labeled as luminal A, luminal B, HER2, and triple-negative. Survival from brain metastases with and without systemic treatment after WBRT was calculated in 4 subsets. RESULTS: In the entire group, the median survival from brain metastases in patients without and with systemic treatment after WBRT was 3 and 10 months, respectively (P < .0001). In the triple-negative subset, the median survival from brain metastases with and without systemic treatment was 4 and 3 months (P = .16), and in the luminal A subset, it was 12 and 3 months, respectively (P = .003). In the luminal B subset, the median survival without further treatment, after chemotherapy and/or hormonal therapy, and after chemotherapy and/or hormonal therapy with targeted therapy was 2 months, 9 months, and 15 months, respectively (P < .0001). In the HER2 subset, the median survival was 4 months, 6 months, and 13 months, respectively (P < .0001). No significant response to systemic treatment was noted in the triple-negative breast cancer population. CONCLUSIONS: Systemic therapy, ordered after WBRT, appears to improve survival in patients with the luminal A, luminal B, and HER2 breast cancer subtypes. Targeted therapy was found to have an additional positive impact on survival. In patients with triple-negative breast cancer, the role of systemic treatment after WBRT appears to be less clear, and therefore this issue requires further investigation. Cancer 2010. © 2010 American Cancer Society. [source]

Phase 2 trial of combination thalidomide plus temozolomide in patients with metastatic malignant melanoma: Southwest Oncology Group S0508,

CANCER, Issue 2 2010
Joseph I. Clark MD
Abstract BACKGROUND: In limited institution phase 2 studies, thalidomide and temozolomide has yielded response rates (RRs) up to 32% for advanced melanoma, leading to the use of this combination as "standard" by some. We conducted a multicenter phase 2 trial to better define the clinical efficacy of thalidomide and temozolomide and the immune modulatory effects of thalidomide, when combined with temozolomide, in patients with metastatic melanoma. METHODS: Patients must have had stage IV cutaneous melanoma, no active brain metastases, Zubrod PS 0-1, up to 1 prior systemic therapy excluding thalidomide, temozolomide, or dacarbazine, adequate organ function, and given informed consent. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included overall survival (OS), RR, toxicities, and assessment of relationships between biomarkers and clinical outcomes. Patients received thalidomide (200 mg/d escalated to 400 mg/d for patients <70, or 100 mg/d escalated to 250 mg/d for patients ,70) plus temozolomide (75 mg/m2/d × 6 weeks, and then 2 weeks rest). RESULTS: Sixty-four patients were enrolled; 2 refused treatment. The 6-month PFS was 15% (95% confidence interval [CI], 6%-23%), the 1-year OS was 35% (95% CI, 24%-47%), and the RR was 13% (95% CI, 5%-25%), all partial. One treatment-related death occurred from myocardial infarction; 3 other grade 4 events occurred, including pulmonary embolism, neutropenia, and central nervous system (CNS) ischemia. There was no significant correlation between biomarkers and PFS or OS. CONCLUSIONS: This combination of thalidomide and temozolomide does not appear to have a clinical benefit that exceeds dacarbazine alone. We would not recommend it further for phase 3 trials or for standard community use. Cancer 2010. © 2010 American Cancer Society. [source]

Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma

CANCER, Issue 8 2008
A phase II Cytokine Working Group study
Abstract BACKGROUND. The combination of temozolomide (TMZ) and thalidomide was reported to produce a high response rate, including shrinkage of brain metastases, in patients with metastatic melanoma. The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma. METHODS. Patients with melanoma, CNS metastases documented by magnetic resonance imaging, and no prior systemic chemotherapy received WBRT, 30 Gray in 10 fractions, Days 1 to 5 and 8 to 12; TMZ, 75 mg/m2/day, Weeks 1 to 6; and thalidomide, 100 mg/day, Weeks 1 to 4, then escalated by 100 mg/day at Weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at Week 10. Patients without CNS or clinically significant systemic disease progression received additional cycles of TMZ at 10-week intervals. RESULTS. Thirty-nine patients received treatment, and 3 exhibited CNS response (1 complete response, 2 partial responses) (response rate, 7.6%; 95% confidence interval, 0.7%-16.1%), all unconfirmed by repeat imaging. Seven patients had stable CNS disease at 10 weeks. No patient exhibited a systemic response. Only 4 patients received 2 cycles of therapy, and just 1 received 3. Median time to progression was 7 weeks, and median overall survival was 4 months. Grade 3-4 side effects included deep venous thrombosis (3), pulmonary embolism (1), and CNS events (12). Eighteen (45%) patients required admission for side effects (7) and/or symptomatic disease progression (11). CONCLUSIONS. The efficacy of TMZ, thalidomide, and WBRT in the treatment of CNS metastatic melanoma is low. Other treatment approaches should be considered for this patient population. Cancer 2008. © 2008 American Cancer Society. [source]

Combined treatment with pegylated interferon,,-2a and dacarbazine in patients with advanced metastatic melanoma

CANCER, Issue 6 2008
A phase 2 study
Abstract BACKGROUND. Dacarbazine (DTIC) and pegylated interferon (IFN),,-2a have both demonstrated some efficacy as single agents in metastatic melanoma. To the authors' knowledge, the current study is the first to test a combination of these 2 agents in a phase 2 trial. METHODS. Twenty,eight patients with stage IV melanoma without brain metastases were treated with DTIC (at a dose of 850 mg/m2 every 3 weeks) combined with weekly pegylated IFN,,-2a at a dose of 180 ,g. The study was initiated to evaluate the efficacy and tolerability of the combination. The primary study endpoint was objective response. RESULTS. Twenty,five patients were evaluable for response. Two patients (8.0%) achieved a complete response that continued for >480 days and 746 days, respectively. Four patients (16.0%) demonstrated a partial response, and another patient experienced stable disease. Six of 7 nonprogressive patients had either not received treatment or had not developed disease progression during adjuvant IFN treatment for stage II/III disease. The median duration of response was 236 days, the median progression-free survival was 56 days, and the overall survival time was 403 days. Few grade 3 toxicities and only 1 grade 4 toxicity were observed (according to National Cancer Institute Common Toxicity Criteria). CONCLUSIONS. The combination of DTIC and pegylated IFN,,-2a was found to be well tolerated in patients with metastatic melanoma. The response rate of 24%, including 2 long-lasting complete responses, is encouraging, but must be confirmed in larger trials. Cancer 2008. © 2008 American Cancer Society. [source]

Survival in patients with brain metastases from breast cancer

A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions,

CANCER, Issue 3 2008
Michael T. Milano MD
Abstract BACKGROUND. It is hypothesized that oligometastatic disease represents a state of potentially curable, limited metastases. Stereotactic body radiation therapy (SBRT) is an option for patients who are not amenable to or do not want resection. METHODS. From 2001 to 2006, 121 patients with ,5 detectable metastases were enrolled in 2 prospective studies that used curative-intent SBRT. Most patients were treated with 10 fractions of 5 Gray. Stereotactic radiosurgery was offered to patients with brain metastases. RESULTS. The 2-year overall survival (OS), progression-free survival (PFS), local control (LC), and distant control (DC) rates were 50%, 26%, 67%, and 34%, respectively; and the respective 4-year rates values were 28%, 20%, 60%, and 25%. A greater net tumor volume predicted significantly worse OS, PFS, LC, and DC. Patients with breast cancer fared significantly better with respect to OS, PFS, LC, and DC; and patients with adrenal metastases had significantly worse OS, PFS, and DC despite the small number of such patients enrolled. Neither the number of metastatic lesions nor the number of organs involved was a significant predictor of outcome. Among 45 patients who remained alive at the last follow-up, 29 patients had no evidence of disease, including 23 patients with ,2 years of follow-up. CONCLUSIONS. Oligometastatic disease is a potentially curable state of distant cancer spread. In this hypothesis-generating analysis, patients with less volume burden of their metastatic disease and those with primary breast cancer fared better. SBRT delivered with curative intent in patients with limited metastases should be investigated further. The Southwest Oncology Group is developing a prospective protocol to treat women who have limited breast cancer metastases with SBRT. Cancer 2008. © 2007 American Cancer Society. [source]

Whole-brain radiotherapy versus stereotactic radiosurgery for patients in recursive partitioning analysis classes 1 and 2 with 1 to 3 brain metastases

CANCER, Issue 10 2007
Dirk Rades MD
Abstract BACKGROUND. The authors investigated whether stereotactic radiosurgery (SRS) alone improved outcomes for patients in recursive partitioning analysis (RPA) Classes 1 and 2 who had 1 to 3 brain metastases compared with whole-brain radiotherapy (WBRT). METHODS. Data regarding 186 patients in RPA Classes 1 and 2 who had 1 to 3 brain metastases and who received either 30 to 40 grays (Gy) of WBRT (n = 91 patients) or 18 to 25 Gy SRS (n = 95 patients) were analyzed retrospectively. Eight other potential prognostic factors were evaluated regarding overall survival (OS), entire brain control (BC), local control (LC) of treated metastases, and brain control distant from treated metastases (distant control [DC]): Those 8 factors were age, sex, performance status, tumor type, number of brain metastases, extracranial metastases, RPA class, and interval from tumor diagnosis to radiotherapy. RESULTS. On multivariate analysis of OS, age ( risk ratio [RR], 1.51; P = .024), Karnofsky performance status (KPS) (RR, 1.98; P = .002), and extracranial metastases (RR, 2.26; P < .001) were significant, whereas the radiation regimen was not significant (P = .89). On multivariate analysis of BC, only the radiation regimen (RR, 1.33; P = .003) was found to be significant. On multivariate analysis of LC, radiation regimen (RR, 1.63; P < .001) and sex (RR, 1.62; P = .022) were significant. On multivariate analysis of DC, KPS (RR, 1.85; P = .049) and extracranial metastases (RR, 1.69; P = .047) were significant. The radiation regimen was not found to be significant even on univariate analysis (P = .80). In RPA class subgroup analyses, BC and LC were better after SRS than WBRT for patients in RPA Classes 1 and 2, whereas OS and DC did not differ significantly. CONCLUSIONS. For patients in RPA Classes 1 and 2 who had 1 to 3 brain metastases, SRS alone was associated with improved BC and LC compared with 30 to 40 Gy WBRT, whereas OS and DC were not significantly different. Similar results were observed in separate subgroup analyses of patients in RPA Class 1 and RPA Class 2. Cancer 2007. © 2007 American Cancer Society. [source]

A boost in addition to whole-brain radiotherapy improves patient outcome after resection of 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients

CANCER, Issue 7 2007
Dirk Rades MD
Abstract BACKGROUND. The current study was conducted to compare 2 treatment regimens including surgical resection and whole-brain radiotherapy (WBRT) for patients with 1 to 2 brain metastases. METHODS. A total of 201 patients with recursive partitioning analysis (RPA) class 1 to 2 disease with 1 to 2 resectable brain metastases were analyzed retrospectively. Patients underwent either resection of the metastases plus WBRT with 10 fractions of 3 grays (Gy) each or 20 fractions of 2 Gy each (99 patients; Group A) or the same treatment plus a WBRT boost to the metastatic site (10 fractions of 3 Gy each plus 5 fractions of 3 Gy each or 20 fractions of 2 Gy each plus 5 fractions of 2 Gy each) (102 patients; Group B). Eight other potential prognostic factors were evaluated with regard to overall survival (OS), brain control (BC), and local control of resected metastases (LC): age, gender, Karnofsky performance status, extent of surgical resection, tumor type, extracranial metastases, RPA class, and interval from tumor diagnosis to WBRT. RESULTS. Group B patients had better 1-year OS (66% vs 41%; P < .001). On multivariate analysis of OS, treatment regimen (relative risk [RR] of 1.94; P < .001), extent of surgical resection (RR of 1.80; P = .001), and interval from tumor diagnosis to WBRT (RR of 1.62; P = .010) were found to be statistically significant. On multivariate analysis of BC, treatment regimen (RR of 2.15; P = .002), extent of surgical resection (RR of 2.78; P < .001), and interval from tumor diagnosis to WBRT (RR of 1.52; P = .034) were found to be statistically significant. On multivariate analysis of LC, treatment regimen (RR of 2.31; P = .002) and extent of surgical resection (RR of 3.79; P < .001) were found to be statistically significant. On RPA class subgroup analyses, outcome was found to be significantly better with a WBRT boost in both RPA class 1 and class 2 patients. A WBRT boost resulted in better outcome after both complete and incomplete surgical resection. However, the results concerning BC and LC were not found to be statistically significant if surgical resection was incomplete. CONCLUSIONS. After surgical resection of 1 to 2 brain metastases, a boost of 10 to 15 Gy in addition to WBRT was found to improve outcome. After incomplete surgical resection, further dose escalation to the metastatic site may be considered. Cancer 2007. © 2007 American Cancer Society. [source]

Temozolomide in advanced malignant melanoma with small brain metastases

CANCER, Issue 2 2007
Can we Withhold Cranial Irradiation?
Abstract BACKGROUND. The efficacy of radiotherapy (RT) in patients who have brain metastases from melanoma is limited. In this study, the authors evaluated the efficacy of treatment with temozolomide in patients with metastatic melanoma, including small brain metastases, who did not require immediate RT and investigated the feasibility of deferring RT. METHODS. Patients with brain metastasis were identified from 3 prospective studies of temozolomide (with or without immunotherapy) for metastatic melanoma. Patients with brain metastasis that measured >2 cm, extensive edema, and localization in the brain stem were excluded from the study. For the current analysis, patients with leptomeningeal metastasis and patients who received previous stereotactic RT were excluded. In patients who achieved a systemic response or stabilization to temozolomide, the response of brain metastasis and the necessity for palliative cranial RT were evaluated. RESULTS. Among 179 patients who received temozolomide for advanced melanoma, 52 patients with brain metastasis were evaluable. Stabilization of systemic metastasis was noted in 7 of 52 patients (13%), and there were 6 responses (5 partial responses and 1 complete response; 11%); thus, in those 13 patients, 6 had stabilization of brain metastasis (11%) and 5 had a response (2 partial responses and 3 complete responses; 9%). Immunotherapy did not influence the neurologic response. The median time to neurologic progression was 7 months (range 2,15, months). RT for cerebral recurrence was required in 2 patients. The median survival of patients with brain metastases was 5.6 months (95% confidence interval, 4.4,6.8 months). Intracranial hemorrhagic complications were not observed. CONCLUSIONS. The current results indicated that it is feasible to treat patients who have advanced melanoma and small brain metastasis with temozolomide as the single treatment. The small subset of patients with systemic response usually showed durable stabilization or a response of brain metastasis. With this approach, neurologic disease can be controlled, and cranial irradiation may be deferred and even withheld in most of patients. Cancer 2007. © 2006 American Cancer Society. [source]

High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib

CANCER, Issue 11 2005
Antonio M. P. Omuro M.D.
Abstract BACKGROUND Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor that induces an early and dramatic response in 10% of patients with advanced nonsmall cell lung carcinoma (NSCLC). Long- term outcome and patterns of disease recurrence after response have not been described. METHODS The authors evaluated 139 patients with NSCLC treated with gefitinib at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1998 and 2002. They focused on patterns of disease recurrence, risk of brain metastases (BM) and leptomeningeal metastasis (LM), and long-term outcome after initial response to gefitinib. RESULTS Of the 139 patients treated with gefitinib, 21 (15%) achieved a partial response. The median age of the responders was 64 years (range, 38,87 years), the median Karnofsky performance score was 80 (range, 60,90), and 4 of the patients were men. All responders had adenocarcinoma. The central nervous system (CNS) was the initial site of disease recurrence in 7 (33%) patients (BM in 5 and LM in 2). In 9 (43%) patients, the initial site of disease recurrence was the lung and in 1 it was the liver and bone. Four (57%) of the patients with disease recurrence in the CNS had lung disease under control. BM also developed in 2 patients who had initial disease recurrence in the lungs. The actuarial 5-year incidence of CNS metastases was 60%. The median overall survival periods were 15 months and 23 months for patients with and without CNS metastases, respectively (P = 0.24). CONCLUSIONS The CNS was a frequent site of disease recurrence in patients with NSCLC after an initial response to gefitinib, regardless of disease control in the lungs. Patients should be carefully monitored for neurologic symptoms. Intrinsic resistance of metastatic clones, incomplete CNS penetrance of the drug, and longer survival are possible explanations for this high incidence. Cancer 2005. © 2005 American Cancer Society. [source]

Survival by radiation therapy oncology group recursive partitioning analysis class and treatment modality in patients with brain metastases from malignant melanoma

CANCER, Issue 8 2002
A retrospective study
Abstract BACKGROUND In a population of patients with brain metastases from melanoma, the authors sought to determine whether various therapies provided any benefit at all, whether local therapy was better than whole brain radiotherapy (WBRT), and whether combined local therapy and WBRT provided any advantage over local therapy alone. They also analyzed survival according to a Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) to determine how well the RTOG RPA classes predicted survival in this patient population and whether treatments varied in effectiveness from category to category. METHODS A total of 74 patients with brain metastases from melanoma were treated at The Cleveland Clinic Foundation between 1984 and 1998. For this study, the authors reviewed patient charts and confirmed survival status. Survival was compared by treatment modality (surgical resection, WBRT, stereotactic radiosurgery, or WBRT combined with local therapy). Survival also was compared according to the RTOG RPA prognostic classes (Class 1, Class 2, or Class 3), which has not been validated previously in patients with malignant melanoma. RESULTS The median survival was 5.5 months for all patients. Survival varied significantly by RTOG prognostic class; The median survival was 10.5 months (range, 2.2,99.2 months) for patients in Class 1, 5.9 months (range, 0.2,43.9 months) for patients in Class 2, and 1.8 months (range, 0.1,6.9 months) for patients in Class 3 (P < 0.0001). Survival analysis showed that combined treatment offered significantly better survival (P < 0.0001; combined vs. other). The median survival was 8.8 months (range, 1.8,99.2 months) for the combined therapy group, 4.8 months (range, 1.2,27.8 months) for the local therapy alone group, 2.3 months (range, 0.2,9.6 months) for the WBRT alone group, and 1.1 months (0.1,3.0 months) for the group that received no therapy. CONCLUSIONS Adding WBRT to local therapy may improve survival in this group of patients: Combined therapy was superior to WBRT alone. The RPA classification scheme likely has prognostic value for patients with brain metastases from malignant melanoma. Prospective studies are required to overcome selection bias and confirm these results. Cancer 2002;94:2265,72. © 2002 American Cancer Society. DOI 10.1002/cncr.10426 [source]