Diagnosis Of Cerebral Metastases Research Articles

Progression of tumors with development of cerebral metastases is accompanied by suppression of thyroid and glucocorticoid functions.

e14005 Background: Cutaneous melanoma (CM), breast cancer (BC) and lung cancer (LC) metastasize to the brain most frequently. Early diagnosis of cerebral metastases is challenging and requires new prognostic criteria. Imbalance of thyroid and glucocorticoid hormones changes the growth and development of malignant tumors. The purpose of the study was to identify readily available prognostic criteria for cerebral metastases in cancer patients at various stages of treatment and follow-up. Methods: Blood levels of cortisol and total triiodothyronine (tT3) were determined by RIA (Immunotech, Czech Republic) in patients with BC (n = 50), LC (n = 50) and CM (n = 50) without brain metastases and in patients with BC (n = 25), LC (n = 25) and CM (n = 25) with cerebral metastases. Results: Blood levels of cortisol in BC, LC and CM patients were normal in 63-84% and elevated on average by 1.7 times in 16-37%. Levels of tT3 in LC were normal, and in BC and CM – within the normal limits, but 1.3 times lower than the mean values. In patients with cerebral metastases, cortisol was lower than the norm by 4.9, 2.5 and 3.6 times in 36% BC, 75% LC and 45% CM cases, respectively. Levels of tT3 in all patients with cerebral metastases were lower than the norm or values in patients without metastases by 2 times and lower. Conclusions: Decreased levels of both cortisol and tT3 in patients with BC, LC and CM may serve as one of prognostic markers of possible development of cerebral metastases. The dynamic determination of levels of thyroid and glucocorticoid hormones is required in cancer patients at various stages of treatment and follow-up.

Brain metastases-Interdisciplinary approach towards a personalized treatment

The incidence, treatment and prognosis of patients with brain metastases have substantially changed during the last decades. While the survival time after diagnosis of cerebral metastases was on average amaximum of 3-6months only 10years ago, the survival time could be significantly improved due to novel surgical, radiotherapeutic and systemic treatment modalities. Only afew years ago, the occurrence of brain metastases led to a withdrawal from systemic oncological treatment and the exclusion of drug therapy studies and to apurely palliatively oriented treatment in the sense of whole brain radiation therapy (WBRT) with or without surgery. The increasing availability of targeted and immunomodulatory drugs as well as adapted radio-oncological procedures enable increasingly more personalized treatment approaches. The aim of this review article is to demonstrate the progress and complexity of the treatment of brain metastases in the context of modern comprehensive interdisciplinary concepts.

EPID-04. THE SINGLE CENTER STUDY FOR BRAIN METASTASES OF UNDIAGNOSED PRIMARY TUMOR AND THE ROLE OF SURGICAL REMOVAL

Abstract BACKGROUND The diagnosis of a brain metastases is generally made during the follow up examinations of patients with primary known cancer. However, there are some patients presenting brain metastases as the first manifestation of a previously undiagnosed primary tumor (UDP) pathological confirmation of the diagnosis. The timing of a subsequent neurosurgical intervention is influenced by the distribution of primary tumors in UDP patients. The purpose of this study was to investigate the optimal diagnostic approach and the role of surgery for UDP patients. METHODS In a retrospective study, 35 patients admitted to our institution and underwent brain tumor removal from 2017 to 2019 with the diagnosis of cerebral metastases and diagnosed lung cancer as primary tumor subsequently, or previously diagnosed lung cancer. RESULTS UDP patients represented 46% of the whole group. Primary tumor subtype was the adenocarcinoma (n=13, 81%), small cell carcinoma (n=2, 13%), and neuroendocrine carcinoma (n=1, 6%). They did not have bronchoscopy nor excision of lung cancer. On the other hand, the patients previously diagnosed lung cancer represented 54% and subtype was adenocarcinoma (n=14, 74%) and small cell carcinoma (n=5, 26%). EGFR mutation was detected from 7 patients (44%) in UDP group and treated by EGFR tyrosine kinase inhibitor. CONCLUSION The significance of surgical intervention in metastatic brain tumors has been limited. However, active surgical intervention in UDP patients could identify not only histological diagnosis but also molecular biological characteristics. Our study suggests the possibility to avoid whole brain radiation in UDP patient by the active surgery.

MULTIPLE CEREBRAL MELANOMA METASTASES WITH UNKNOWN PRIMARY TUMOR LOCATION: A CASE REPORT

Introduction. Diagnostic and therapeutic approach of multiple cerebral lesions is often challenging. Case report. A 66-year-old man with unremarkable medical history was admitted to our hospital for recent inability and stereotyped movements of the left upper limb. Brain MRI identified eight tumoral masses with contrast enhancement and marked SWI signal loss that displayed increased metabolic activity on 18F-FDG PET/CT scan. Cerebral biopsy led to the diagnosis of melanoma with BRAF V600E mutation. Stereotactic radiosurgery and molecular therapy were planned afterwards. Conclusion. Brain MRI is an useful tool in guiding diagnosis of cerebral metastases of unknown origin.

Development of brain metastases in patients with metastatic melanoma while receiving ipilimumab.

Ipilimumab is a monoclonal antibody blocking the inhibitory molecule CTLA4 expressed by activated T lympocytes, used for the treatment of metastatic melanoma. Recent studies have shown its potential efficacy on brain metastases. To assess the development of brain metastases under ipilimumab and identify clinical, histological or evolving criteria related to the appearance of these metastases. A retrospective study was conducted in 52 patients treated with 4 cycles of ipilimumab 3 mg/kg every 3 weeks for unresectable stage III or stage IV melanoma between January 2011 and July 2013 in a Department of Dermato-Oncology. As no data has been find in the literature, the results were compared to our other cohort of patients treated with vemurafenib during the same period. Ten patients (21.7 %) developed brain metastases under ipilimumab in a median time of 6.58 months after treatment initiation. The multivariate analysis showed a lower rate of brain metastases in patients with acral lentiginous melanoma and melanoma of unknown primary site. The median survival after diagnosis of brain metastases was of 2.5 months. There was no significant difference with vemurafenib-treated patients in terms of incidence rate of brain metastasis, time of development and survival after diagnosis of cerebral metastases. This was the first study focused on the development of brain metastases under treatment with ipilimumab 3 mg/kg. Although ipilimumab is used for the treatment of brain metastases, it paradoxically did not seem to reduce the risk of developing brain metastases.

Management of Cerebral Metastases from Melanoma Treated at a Single Institution

Objective This retrospective study aimed to analyze prognostic factors, effects of treatment, and survival outcome of patients with brain metastasis from melanoma at a single institution over the last 22 years. Methods Study transversal retrospective of 34 patients with brain metastases from melanoma, histologically proven, surgically treated by the Department of Neurosurgery at the Hospital Santa Isabel, Blumenau, over 22 years. Results The median patient age was 50 years and 67.6% of the patients were men. Most patients (70.6%) had a single cerebral metastasis and 29.4% had two three injuries. Twenty percent of the patients in this series had evidence of extracranial metastasis. The KPS at presentation was ≥70 in 12 patients (35.2%). Evidence of recurrent intracranial melanoma was found during follow-up review in 17.6% of patients. The overall median survival time from diagnosis of cerebral metastasis was 14.4 months. The absence of extracranial metastasis was associated with a significantly prolonged survival ( p = 0.052), as was adjuvant therapy ( p = 0.02). Conclusion The early diagnosis, with total resection of melanoma metastasis and association of adjuvant therapies showed a positive influence on survival. However, the number of lesions and extracranial disease decreased the survival rates.

Enhanced White Adipose Tissue Metabolism in Iatrogenic Cushing's Syndrome With FDG PET/CT

A 35-year-old man commenced high-dose dexamethasone (16 mg/d) at diagnosis of cerebral metastases from non-small cell lung carcinoma. F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/ computed tomography (CT) performed 9 days later (Figure 1) was nondiagnostic due to widespread abnormally increased FDG-uptake in sc and visceral white adipose tissue (WAT). Comparison with baseline CT demonstrated rapid interval growth of ectopic WAT in a Cushingoid distribution (Figure 2). Prominent sc and visceral WAT FDG uptake was also evident in a 14-year-old boy with Hodgkin lymphoma imaged 6 days after commencement of high-dose prednisolone (75 mg/d). Glucocorticoids induce “catabolic” lipolysis, “anabolic” lipogenesis (adipocyte hypertrophy), and adipogenesis (adipocyte hyperplasia) to remodel WAT into the characteristic Cushingoid distribution (1). Dexamethasone-induced adipocyte differentiation (2) required for ectopic WAT remodeling requires increased glycolytic mitochondrial metabolism (3), and thus ectopic WAT FDG uptake. Increased lipogenesis utilizing glucose as a nonlipid substrate could also explain the widespread WAT FDG uptake in these cases (4). Dexamethasone also induces a proinflammatory milieu within WAT (including raised serum amyloid A) (5), potentially increasing WAT FDG uptake associated with macrophage recruitment. The reduced fasting myocardial and skeletal muscle uptake presumably reflects utilization of high circulating levels of free fatty acids and reduced insulin sensitivity. This is the first description of widespread FDG uptake in WAT after commencement of high-dose glucocorticoids, and it provides unique in vivo insight into the rapid developmentof iatrogenicCushing’s syndrome.However, this uncommon finding is potentially influenced by other factors including age, sex, dosage, and duration of glucocorticoid exposure. The potential utility of FDG PET/CT for assessing WAT metabolism warrants prospective clinical evaluation.

Hirnmetastasen beim Lungenkarzinom

Cerebral metastases are a frequent complication of lung cancer. They often determine patients' prognosis and need urgent therapeutic intervention. Based on histologic type, former therapies, age and performance of the patient, the number of cerebral lesions and the extracerebral tumour activity, individualized treatments are applied. For patients who suffer from non-small cell lung cancer and a single CNS lesion the best results can be achieved if they are surgically resected or receive radiosurgery. Their survival time can be markedly increased in comparison to patients who undergo whole brain irradiation. If multiple metastases are seen in CT or MRI, whole brain irradiation is the therapy to choose. Furthermore it should be initiated if small cell lung cancer metastasizes to the brain. More aggressive local treatment options appear promising, but a clear role for them has not yet been defined. Systemic chemotherapy gains more attention in the treatment of small and non-small cell lung cancer with brain metastases. How to increase the efficacy through simultaneous application of chemo- and radiotherapy is tested in current trials. This article gives an overview on clinical presentation and diagnosis of cerebral metastases in lung cancer and reviews current treatment options.

Hirnmetastasen beim Lungenkarzinom

Cerebral metastases are a frequent complication of lung cancer. They often determine patients' prognosis and need urgent therapeutic intervention. Based on histologic type, former therapies, age and performance of the patient, the number of cerebral lesions and the extracerebral tumour activity, individualized treatments are applied. For patients who suffer from non-small cell lung cancer and a single CNS lesion the best results can be achieved if they are surgically resected or receive radiosurgery. Their survival time can be markedly increased in comparison to patients who undergo whole brain irradiation. If multiple metastases are seen in CT or MRI, whole brain irradiation is the therapy to choose. Furthermore it should be initiated if small cell lung cancer metastasizes to the brain. More aggressive local treatment options appear promising, but a clear role for them has not yet been defined. Systemic chemotherapy gains more attention in the treatment of small and non-small cell lung cancer with brain metastases. How to increase the efficacy through simultaneous application of chemo- and radiotherapy is tested in current trials. This article gives an overview on clinical presentation and diagnosis of cerebral metastases in lung cancer and reviews current treatment options.

Clinical presentation, treatment and outcome of patients with cerebral metastases: the University of São Paulo series.

Secondary neoplasias are the most common tumors affecting the central nervous system and several clinical aspects of this disease are still controversial. Forty-seven consecutive patients with the diagnosis of cerebral metastases (CM) were retrospectively studied at the Clinical Hospital of Sao Paulo University Medical School. Mean age was 53.9 years and 25 patients were female. The most frequent primary sites were breast, lung and skin. Symptoms were related to increased intracranial pressure (ICP) in 48.9%, focal neurological events in 27.7% and both in 17.0%. Single brain metastases were found in 57.4% of those cases, the frontal lobe being most frequently affected. Surgical treatment was performed in 68.1%, radiotherapy in 40.4% and chemotherapy in 17.0%. After statistical analysis, there was a trend towards prolonged survival of female patients, patients with ICP symptoms and the surgical group. Data from different centers are essential to establish the best management of CM.

Unusual Metastatic Features in a Patient with Concomitant Malignant Orbital Melanoma and Prostate Carcinoma

A 73-year-old man with a history of malignant orbital melanoma and prostate carcinoma was admitted for progressive visual disturbance. Brain magnetic resonance imaging showed a suprasellar enhancing nodular lesion with major impingement on the anterior optical ways and sellar invasion. The extensive imaging work-up could not demonstrate with certainty its origin. Surprisingly, the transphenoidal biopsy of this patient revealed a prostate cancer metastasis outlining the importance of a histopathological diagnosis of cerebral metastases in patients with multiple malignancies when there is a doubt about the nature of the lesion.

The origin of brain metastases in patients with an undiagnosed primary tumour.

In patients presenting brain metastases as the first manifestation of a previously undiagnosed primary tumour (UDP) histopathological confirmation of the diagnosis can be obtained by either direct surgical sampling of the brain lesion or paraclinical search for an accessible primary tumour. The sequence of the diagnostic work-up and the timing of an eventual neurosurgical intervention are a matter of debate and are mainly influenced by the distribution of primary tumours in UDP patients. The aim of this study was to verify the hypothesis that the distribution of primary tumours differs between UDP patients and the rest of the patients with brain metastases (DP), and to propose a diagnostic work-up specifically tailored to the UDP population. Retrospective study on 342 patients admitted to the Lausanne University hospital between 1983 and 1998 with the diagnosis of cerebral metastases. UDP patients represented 36% of the whole group. Primary tumour location was significantly different between the two groups (p=0.001). Although the lung was the most frequent primary tumour location in both groups (UDP: 60%, DP: 43%), in UDP 14% only of the primaries were found outside of the lung and as much as 26% remained unknown despite thorough investigations. Our study confirmed the hypothesis that the relative frequency of primary tumours differs between DP and UDP patients. This difference therefore mandates a diagnostic strategy specifically tailored for UDP patients: if a radiological lung investigation clearly remains the best initial step in the work-up of these patients, extensive paraclinical investigations without a clear clinical suspicion should probably not be undertaken if this first survey fails to disclose the primary tumour as only 14% of the patients will actually benefit from it. In this situation, a neurosurgical procedure should probably be considered the most appropriate next step to be taken in order to provide a definitive diagnosis without unnecessary delays.

Cerebral metastases. Review of a hospital population

Cerebral Metastases are diagnosed in approximately 20-30% of patients with primary tumours. Because of the improvement of central nervous system imagining technology and of the newly effective therapeutic schemes, the incidence of this particular type of cerebral lesion tends to increase. In this retrospective study the authors review the patients admitted in the Neurology, Neurosurgery and Medicine departments and in the outpatient chemotherapy consultation, with a diagnosis of cerebral metastases. Sex and age, neurologic symptoms at presentation, neuroradiologic findings, primary tumour origin, treatment outcomes and prognosis were evaluated in this population.

Cerebral metastases from ovarian carcinoma

Apart from choriocarcinoma, involvement of the central nervous system (CNS) by gynecologic malignancy is rare. A 10-year retrospective review at the University of Washington Medical Center (Seattle, WA) and Swedish Hospital and Medical Center Tumor Registry (Seattle, WA) identified 14 patients with cerebral metastases from ovarian carcinoma. Median age at diagnosis of cerebral metastases was 52.5 years. Median interval from the diagnosis of ovarian carcinoma to the diagnosis of CNS metastases was 14.5 months. Seven patients had received cisplatin therapy before CNS relapse. Seven patients underwent second-look procedures before developing CNS metastases; in three, results were negative. Eight patients had evidence of extraperitoneal spread to other sites at the time of CNS relapse. Clinical manifestations included motor weakness, seizures, headache, confusion, and speech disturbance. All lesions were contrast enhancing on computed tomography (CT) scans and were located in the cerebral hemispheres. Nine patients had single lesions, five of whom underwent surgical resection of the lesion with histologic confirmation of metastases from the primary site. Median survival was 2 months in patients receiving radiation therapy alone and 17 months in patients who received surgery and radiation. Median survival of the entire series was 3 months. The presence of multiple cerebral metastases or evidence of extraperitoneal spread elsewhere in the body was adversely associated with survival. The prognosis of patients with cerebral metastases from ovarian carcinoma appears poor. However, early diagnosis by routine CT scanning followed by surgical resection and radiation may improve overall survival in a select group of patients.

Surgical treatment of brain metastases from renal cell carcinoma

Between January 1976 and December 1986, 22 patients with renal cell carcinoma underwent surgical resection of brain metastases at Memorial Sloan-Kettering Cancer Center. Ten of the patients had metastases limited to the brain and 12 also had extracranial metastases. Twenty patients received external radiotherapy. Five had craniotomy after failing radiation therapy and 15 had adjuvant radiotherapy. Two patients died within thirty days following craniotomy; the median survival of the remaining 20 patients was 20.9 +/- 6.8 months calculated according to a Weibull survival model. Variables examined in relation to survival included absence or presence of extracranial metastases at time of craniotomy, time interval between nephrectomy and diagnosis of cerebral metastases, neurologic status prior to craniotomy, location of the brain tumor, and patient age. None of the variables was significant at the 10 percent level by the Weibull analysis. However, three favorable prognostic factors, namely metachronous brain metastasis more than one year after nephrectomy, minimal or no neurologic deficit at time of craniotomy, and infratentorial lesions show a trend toward improved survival with p less than 0.20. The data suggest that surgical resection of a single and occasionally multiple brain metastases is warranted in selected patients with renal cell carcinoma.

Cerebral metastases in patients with ovarian cancer treated with chemotherapy

Cerebral metastases are considered an uncommon complication of ovarian carcinoma. In a series of 52 patients treated with platinum, Adriamycin, and cyclophosphamide combination chemotherapy, 6 patients developed cerebral metastases, an incidence (11.6%) higher than that reported by others. The median age of the patients with cerebral metastases was similar to that of patients without this complication. Cerebral metastases occurred as site of first relapse in three of six patients. Only one patient had extraperitoneal disease prior to chemotherapy and four of the six patients had attained a complete response following chemotherapy. Cerebral relapse occurred at 0, 21, 27, 30, 34, and 36 months from original diagnosis of ovarian carcinoma and 0, 9, 11, 19, 25 and 29 months following first treatment with combination chemotherapy. The median survival was 33 months from diagnosis and 28.5 months from first treatment with chemotherapy. This compares with a median survival from diagnosis for the entire series of 30 months (28 months from first treatment). The result of treatment of established metastases was poor. Survival from diagnosis of cerebral metastases was 2, 2, 3, 6, 10, and 41 + months. If other series confirm these findings consideration may need to be given to prophylactic central nervous system radiotherapy for patients achieving complete remission after systemic chemotherapy.

Cerebral metastases in patients with ovarian cancer treated with chemotherapy

Cerebral metastases are considered an uncommon complication of ovarian carcinoma. In a series of 52 patients treated with platinum, Adriamycin, and cyclophosphamide combination chemotherapy, 6 patients developed cerebral metastases, an incidence (11.6%) higher than that reported by others. The median age of the patients with cerebral metastases was similar to that of patients without this complication. Cerebral metastases occurred as site of first relapse in three of six patients. Only one patient had extraperitoneal disease prior to chemotherapy and four of the six patients had attained a complete response following chemotherapy. Cerebral relapse occurred at 0, 21, 27, 30, 34, and 36 months from original diagnosis of ovarian carcinoma and 0, 9, 11, 19, 25 and 29 months following first treatment with combination chemotherapy. The median survival was 33 months from diagnosis and 28.5 months from first treatment with chemotherapy. This compares with a median survival from diagnosis for the entire series of 30 months (28 months from first treatment). The result of treatment of established metastases was poor. Survival from diagnosis of cerebral metastases was 2, 2, 3, 6, 10, and 41 + months. If other series confirm these findings consideration may need to be given to prophylactic central nervous system radiotherapy for patients achieving complete remission after systemic chemotherapy.

Computerized axial tomography in the diagnosis of cerebral metastases

The importance of CT scan in the diagnosis of cerebral metastases cannot be disputed. Four hundred and thirty two metastases were found in 188 patients. The aspects of the masses may vary in two ways after injection: homogeneous or ring-like enhancement. Ring-like appearance is often discovered in the biggest masses most likely due to an area of necrosis within it. The size and number of metastases are variable, an area of edema often accompanies one of the masses. When there is only one mass, differential diagnosis is more difficult and clinical data are very important.

Brain metastases in malignant teratoma: a review of four years' experience and an assessment of the role of tumour markers.

Between 1973 and 1977, 247 patients with malignant teratoma have been treated in two units in London. Seventeen have developed brain metastases, an overall incidence of 6.2%. The median survival from diagnosis of cerebral metastases is 6 weeks and all patients except one have died. The survivor is disease-free 12 months after completing treatment, which included extensive use of chemotherapy, surgery and radiotherapy. Serum gonadotrophin (HCG) and alpha-foetoprotein (AFP) estimations have been performed in 264 patients as a means of monitoring the effects of therapy. In 42 patients (37 of whom had Stage IV disease) the peak HCG level was greater than 10(4) iu/l, and the incidence of brain metastases in this group was 26%, significantly higher than in the group with HCG levels below 10(4) iu/l, for which the incidence of cerebral deposits was 1.8% (P less than 0.0001). No significant correlation was seen between peak AFP levels and the incidence of brain metastasis. With the aim of improving results by earlier diagnosis, cerebrospinal fluid (CSF) specimens have been examined for HCG and AFP levels in 56 subjects, 9 of whom had brain metastases. A serum: CSF HCG ratio less than 40 is an accurate indication of the presence of brain metastases, and may have considerable predictive value. However, false-negative serum: CSF HCG rations (greater than 40) frequently occur in patients with proven brain deposits. Estimation of AFP in spinal fluid has not contributed to the early diagnosis of brain metastases in malignant teratoma.

Diagnostic problems of cerebral metastases.

1. The diagnosis of cerebral metastasis is very probable when a primary tumour in another body organ has been identified. — 2. Diagnosis is also very probable in the presence of multiple intracranial tumours which, except in the exceptional cases of multiple neurinomas and multiple meningiomas, are always metastatic. — 3. Diagnosis of metastasis is probable in the presence of an abnormal vascularity of the “rim” or “blot” type. — 4. Diagnosis of metastasis can also be tentatively made in the presence of an abnormal vascularity, meningioma or glioblastoma type, on the basis of the form, size and type of outline. — 5. In all other cases, differential diagnosis between metastases and intracranial primary tumours is impossible.