Appearance Of Brain Metastases Research Articles

Epidemiological, diagnostic and therapeutic profile of cerebral tumors in the radiotherapy department of Dalal Jamm hospital

Introduction: Brain tumors, whether benign or malignant, primary or secondary, raise public health concerns due to their relative rarity and high mortality and morbidity rates. They account for 1.6% of all cancer cases, with types predominating according to patient age and gender. Brain metastases are more frequent than primary malignant brain tumors. Advances in imaging have improved diagnosis and management, but the constraints of the African context limit access to care. Materials and Methods: This retrospective study included 105 patients with brain tumors treated between June 2018 and October 2022 at the Dalal Jamm Hospital in Guediawaye. Sociodemographic, clinical, radiological, therapeutic and evolutionary data were analyzed. Statistical analysis was performed with SPSS. Results: Of 1,740 patients treated with radiotherapy, 105 had brain tumors. Women were more numerous, with a mean age of 43.17 years. The most common symptoms were related to intracranial hypertension. The majority of patients were in good general condition on admission. The mean time from diagnosis of the primary lesion to the appearance of brain metastases was 48.37 weeks. Magnetic resonance imaging was underused. Secondary brain tumors were frequent, mainly of mammary origin. Radiotherapy was the main treatment, but limited access to radiotherapy centers led to delays. Radiotherapy doses varied according to tumor type. Concomitant chemotherapy was given for high-grade gliomas, but its use was limited due to cost and drug shortages. Palliative chemotherapy was rarely used. Median survival was 3 months.

P393 EDOXABAN: NEW PERSPECTIVE IN A PATIENT WITH CANCER–ASSOCIATED THROMBOSIS COMPLICATED BY BRAIN METASTASES. A RARE CLINICAL CASE

Abstract Herein, we present the case of a 58 y–o Caucasian man with unremarkable cardiovascular history and a strong family history for cancer. He was diagnosed with lung adenocarcinoma IVb (pleura, pleural effusion, lymph nodes), PDL1: 2% TPS and absence of actionable driver mutations on DNA and RNA NGS (only ERBB2 mutation). Started first–line chemotherapy with cisplatin–pemetrexed regimen and immunotherapy with pembrolizumab. He developed common/superficial femoral and popliteal deep vein thrombosis (DVT) and pulmonary embolism (PE). The patient started low–molecular–weight heparin (LMWH) namely enoxaparin 1 mg/kg x 2/d (weight: 65 Kg). After 1 mo, CT showed PE resolution. Due to DVT persistence and patient’s preference for oral administration, LMWH was replaced with direct oral anticoagulant (DOAC) namely edoxaban 60 mg 1 cp/d. After 2 mo, resolution of common femoral and popliteal vein thrombosis with partial recanalization of superficial femoral DVT were detected. However, he developed brain metastases treated with WB radiotherapy. We decided for edoxaban full dose long–term anticoagulant treatment with monthly cardioncological surveillance. After 6 mo since cancer diagnosis, the patient was still adherent to DOAC therapy, although in a maintenance combined regimen pemetrexed–pembrolizumab based, without both drug–drug interactions and brain bleeding. Conclusions Thromboembolism is the second leading cause of death in malignancy. In this clinical case, a man with advanced lung cancer developed extended cancer–associated thrombosis (CAT). However, the appearance of brain metastases has posed a clinical dilemma: to continue or to withdraw the anticoagulant therapy and, also, which drug to choose between LMWH and DOAC. Literature is limited on the use of DOACs in cancer patients with brain metastases. Besides, current guidelines neither advocate contraindication to DOAC, nor suggest caution as requested for gastrointestinal and genitourinary sites of cancer. We decided to proceed with edoxaban therapy, despite chemotherapy combined to immunotherapy were still ongoing and the concurrent appearance of brain metastases, with good results in efficacy, patient’s adherence and, mostly, safety. In conclusion, in regard to our clinical experience, we point out DOAC as a reliable and manageable therapeutical choice in CAT, also in active cancer patients with brain metastases receiving chemo–immunotherapy.

Current approaches to the treatment of metastatic brain tumors

Background/Aim. About 10% of patients diagnosed with systemic cancer leads to the appearance of brain metastases in the central nervous system. Diseased lungs, breasts, urinary and digestive tract as well as melanoma of the skin, are increasingly treated by neurosurgeons due to their dissemination and creation of secondary deposits in the brain. Methods. The retrospective study was performed at the Clinic for Neurosurgery and the Clinic for Oncology in the period from 2018 to 2020. 111 patients with solitary changes in the brain and 122 patients with multiple changes were examined. Results. It was found that multiple metastases are more common in primary lung cancer, while single metastases are more common in adenocarcinoma, but patients with primary adenocarcinoma died in a significantly higher number. Conclusion. Surgery and radiation remain the cornerstone of therapy for symptomatic lesions; We should strive to improve surgical techniques in the direction of less damage to the surrounding healthy tissue. Radiosurgery, as well as VBRT radiation, remain the basic form in the treatment of multiple metastases.

P.141 Does BRAF mutation status or being on systemic therapy alter the radiological appearance of brain metastases in metastatic melanoma?

Background: The aim of this study is to investigate the differences in the radiological appearances of brain metastases (BM) in metastatic melanoma (MM) relative to BRAF mutation status. As well as to compare imaging differences in BM that occur prior to starting and during systemic therapy. Methods: A retrospective study was done over a 5 year period. Patients with MM with BM and known BRAF status were identified. 38 met the inclusion criteria. Imaging features on both Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) were reviewed. Results: Irrespective of BRAF mutation status, BM in MM tended to have a peripheral location with 30/38 cases having BM in the cerebral cortex. BRAF positive MM had a higher frequency of irregularly enhancing BM on CT and higher occurrence of BM showing high T1 signal on MRI. BM found during systemic treatment, regardless of BRAF status, showed less surrounding oedema, were smaller and harder to spot on CT. Conclusions: Understanding imaging features based on genetics could inform future management. The subtle features of BM on CT during systemic therapy means careful follow up with MRI may be indicated to confirm the diagnosis and to more accurately assess the burden of brain disease.

Picturing Breast Cancer Brain Metastasis Development to Unravel Molecular Players and Cellular Crosstalk

Simple SummaryBreast cancer is a devastating disorder affecting millions of women worldwide. With improved therapeutics for the primary tumor, the appearance of metastasis has been increasing. Breast cancer frequently metastasizes to the brain, constituting a major hurdle without cure and with a poor survival. It is imperative to better understand the mechanisms involved in malignant cell transposition of the brain microvasculature and parenchymal colonization by deciphering the alterations occurring in the tumor and microvascular cells, as well as the occurrence of intercellular communication during the process. We aimed to profile the process of the formation of breast cancer brain metastasis and the timeline of events governing it. We used a specific mouse model of the disease to perform extensive microscopic analyses. We identified phenotypic changes and the activation of relevant molecular players in tumorigenesis, together with vascular alterations, and the occurrence of crosstalk. Our findings unravel putative therapeutic targets to tackle breast cancer brain metastasis.With breast cancer (BC) therapy improvements, the appearance of brain metastases has been increasing, representing a life-threatening condition. Brain metastasis formation involves BC cell (BCC) extravasation across the blood–brain barrier (BBB) and brain colonization by unclear mechanisms. We aimed to disclose the actors involved in BC brain metastasis formation, focusing on BCCs’ phenotype, growth factor expression, and signaling pathway activation, correlating with BBB alterations and intercellular communication. Hippocampi of female mice inoculated with 4T1 BCCs were examined over time by hematoxylin-eosin, immunohistochemistry and immunofluorescence. Well-established metastases were observed at seven days, increasing thereafter. BCCs entering brain parenchyma presented mesenchymal, migratory, and proliferative features; however, with time, they increasingly expressed epithelial markers, reflecting a mesenchymal–epithelial transition. BCCs also expressed platelet-derived growth factor-B, β4 integrin, and focal adhesion kinase, suggesting autocrine and/or paracrine regulation with adhesion signaling activation, while balance between Rac1 and RhoA was associated with the motility status. Intercellular communication via gap junctions was clear among BCCs, and between BCCs and endothelial cells. Thrombin accumulation, junctional protein impairment, and vesicular proteins increase reflect BBB alterations related with extravasation. Expression of plasmalemma vesicle-associated protein was increased in BCCs, along with augmented vascularization, whereas pericyte contraction indicated mural cells’ activation. Our results provide further understanding of BC brain metastasis formation, disclosing potential therapeutic targets.

Giant lung metastasis of NRAS-mutant melanoma in a 24-year-old patient with a history of BRAF-mutant conventional melanoma harboring Spitzoid morphology: a case report

BackgroundSpitzoid melanocytic lesions represent a heterogeneous group of proliferations with ambiguous and overlapping terminology. The exact distinction of a Spitz nevus from a Spitzoid melanoma can be very difficult or, in some cases, impossible. Among the Spitzoid lesions, there is a lesion termed an atypical Spitz tumour (AST) that has intermediate histopathologic features between those of a Spitz nevus and a Spitzoid melanoma and thus uncertain malignant potential. There are several rare cases of patients with a Spitzoid melanoma initially misdiagnosed as a Spitz nevus or an AST with fatal consequences. It is, therefore, advised to perform a molecular characterization in cases where uncertain skin lesions are presented, as it may provide extended set of information with a possible impact on the treatment options. Furthermore, preventive measures, such as regular physical and skin examinations, as well as thorough scheduling of individual follow-up visits, are essential in patients with potentially malignant skin nevi.Case reportWe report a case of a young adult female with a history of AST excision with a negative sentinel lymph node biopsy (SLNB) and insufficient follow-up. Four years after the primary dermatological diagnosis, she presented with a giant tumour in the right hemithorax. Radical en bloc resection of the tumour with right pneumonectomy and resection of the pericardium with reconstruction of the pericardium using mesh was performed. A definitive histopathological examination revealed a metastatic melanoma. The association of the previously diagnosed AST and subsequent appearance of melanoma metastases led to a retrospective re-evaluation of the initial lesion. The suspected diagnosis of Spitzoid melanoma, however, was not confirmed. Moreover, the molecular examination revealed a major discordance between the initial lesion and the lung tumour, which most likely excluded the possible association of the lung metastasis with the initial skin lesion. The initial skin lesion was a BRAF-mutant melanoma with Spitzoid features and termed as AST, while the giant lung metastasis was NRAS-mutant melanoma. The subsequent postoperative course was complicated by the appearance of brain metastases that were stereotactically irradiated. Nevertheless, despite complex specialised medical care, the patient’s clinical condition rapidly deteriorated. By this time, no active oncological treatment was possible. The patient was delegated to local hospice for palliative care six months after the surgery and died three weeks later.ConclusionsOur patient was surgically treated at the age of 20 for AST and died four years later of metastatic NRAS-mutant melanoma most likely of different occult origin. Molecular characterization, as well as the close clinical follow-up should be always precisely performed in patients with uncertain skin lesions, such as AST.

CT SCAN AND MRI APPEARANCE OF BRAIN METASTASIS IN LUNG ADENOCARCINOMA PATIENTS WITH EPIDERMAL GROWTH FACTOR RECEPTOR MUTATION STATUS EVALUATION IN DR. SOETOMO GENERAL HOSPITAL JANUARI 2018 – DECEMBER 2019

This study aims to find the prevalence and appearance of brain metastasis from CT and MRI in lung adenocarcinoma with negative and positive EGFR mutation status of exon 19 and 21, with evaluation parameters are location, numbers, presence of miliary lesion, largest size, component, contrast enhancement, and adjacent edema. A descriptive, retrospective study was performed on 119 lung adenocarcinoma patient with EGFR mutation status who underwent underwent head CT or MRI during January 2018 until December 2019. We found 19 (55.9 %) patients with positive EGFR mutation status of exon 19; 13 (48.1 %) patients with positive EGFR mutation status of exon 21; and 20 (37.0 %) patients with negative EGFR mutation status. The CT and MRI of patients with negative and positive EGFR mutation status of exon 19 and 21have similar appearance, with mos common location at corticomedullary, parietal lobe, multiple, with largest size 1.1-2.5 cm and 2.6 cm, solid-necrotic/cystic component, heterogenous ring contrast enhancement, and perifocal edema.

Survival time and prognostic factors after whole-brain radiotherapy of brain metastases from of breast cancer.

BackgroundBreast cancer has a poor prognosis due to the high risk of distant metastasis.PurposeTo identify the prognosticators of brain metastasis from breast cancer treated by whole-brain radiotherapy.Material and MethodsWe evaluated patients diagnosed with primary brain metastasis without carcinomatous meningitis from breast cancer and had undergone whole-brain radiotherapy as initial treatment between 1 January 2010 and 30 September 2019. We investigated associations between overall survival time from diagnosis using cranial contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) and the following parameters: (i) age; (ii) sex; (iii) time to appearance of brain metastasis; (iv) other metastasis at appearance of brain metastasis; (v) blood test; (vi) symptoms at time of brain metastasis; (vii) whole-brain radiotherapy dose; (viii) whether whole-brain radiotherapy was completed; (ix) course of chemo- or radiotherapy; (x) subtype; (xi) additional irradiation after whole-brain radiotherapy; (xii) pathology; and (xiii) imaging findings.ResultsWe evaluated 29 consecutive female patients (mean age 55.2 ± 12.1 years). Median overall survival time after diagnosis on cranial contrast-enhanced MRI/CT was 135 days (range 16–2112 days). Multivariate stepwise analysis of the three parameters of lactate dehydrogenase, dose, and subtype identified the following significant differences: Hazard Ratio (HR) for dose (discontinued, 30 Gy/10 fractions, 31.5 Gy/11 fractions, 32.5 Gy/11 fractions, 37.5 Gy/15 fractions) was 0.08 (95% confidence interval [CI] 0.02–0.30, P < 0.01), and HR for subtype (luminal, HER2, triple-negative) was 2.70 (95% CI 1.16–6.243, P < 0.01).ConclusionHER2-type and 37.5 Gy/15 fractions are good prognostic factor after whole-brain radiotherapy in breast cancer with brain metastases.

Unusual Cystic and Papillary Appearance of Brain Metastasis from Papillary Lung Adenocarcinoma on MRI. Radiologic-Pathologic Correlations in Two Similar Cases

We report two cases of brain metastasis from a lung adenocarcinoma. Magnetic Resonance Imaging (MRI) appearance was closely correlated with the macroscopic and microscopic findings that showed multiples nodules of a well-differentiated papillary adenocarcinoma with secreting tubules, surrounded by mucoid fluid.

Prognostic Value of Brain Metastasis-Free Interval in Patients with Breast Cancer Brain Metastases

In patients with breast cancer brain metastases (BCBM), time between primary tumor diagnosis and appearance of brain metastases varies widely. Despite being a readily available clinical parameter, it remains unclear whether brain metastasis-free interval (BMFI) carries prognostic value among breast cancer patients. The aim of this study was to compare characteristics and overall survival among patients with varying BMFIs and to assess the prognostic role, if any, for BMFI. We retrospectively reviewed 3 institutional databases of adult female patients who were treated for BCBM between 1996 and 2017. Cox proportional hazards model and Kaplan-Meier survival curves were used to determine prognostic value of BMFI for survival. A total of 503 patients were included. Median age at first brain metastasis was 52 (interquartile range [IQR]: 45-58) years. Median BMFI was 38 months (IQR: 18-66), and median overall survival was 17 months (IQR: 8-31). In univariate Cox proportional hazards model, younger age at BCBM, estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)+ tumor subtype, and the absence of liver or lung metastases were associated with longer survival. BMFI >3 years was not associated with longer survival (hazard ratio [HR]= 1.13; P= 0.21). In multivariate analysis, only subtype (ER+/HER2+ vs. ER-/HER2-; HR= 0.77; P=0.02) and liver metastases (HR= 1.36; P= 0.01) were prognostic for survival. There was no significant association between BMFI and overall survival (HR= 0.99; P= 0.91). In this large, retrospective cohort of breast cancer patients, BMFI was not prognostic for overall survival.

The role of surgical resection in patients with brain metastases.

Treatment of brain metastases represent a critical issue and different options have to be considered according to patients and tumour characteristics; in recent years, new therapeutic strategies have been proposed. In this review, we discuss the role of surgical resection on the basis of patient selection, new surgical techniques and the use of intraoperative adjuncts. The integration with postoperative whole brain radiotherapy will be also outlined because alternative treatment options are currently available. Surgical removal has been considered the mainstay in the treatment of brain metastases, in selected patients, with limited number of intracranial lesions and controlled primary disease, mainly in combination with whole brain radiotherapy. In the last few years, the increasing role of stereotactic focal radiotherapy has deeply modified the indications to open surgical procedures and whole brain radiotherapy. The appearance of brain metastases is considered a sign of bad prognosis. Treatment of these lesions is important for quality of life, providing local tumour control, preventing death from neurological causes and improving survival, although potentially only in a minority of patients. Careful patient selection, with adequate evaluation of clinical prognostic score, the use of appropriate surgical techniques and surgical adjuncts are major determinants of favourable outcome in patients undergoing resection of brain metastases.

Fatores prognósticos e tratamento de pacientes com metástases cerebrais

O desenvolvimento de metástases cerebrais é um evento muito freqüente no paciente com câncer, sendo a neoplasia maligna mais prevalente do sistema nervoso central (SNC). O tratamento médico destes pacientes inclui: 1) Medidas inespecíficas, tais como cuidados clínicos gerais (por exemplo, o uso de corticosteróide e drogas anticonvulsivantes, entre outros); 2) Medidas específicas gerais (que tratam todos os possíveis focos de doença no SNC, como radioterapia cerebral total e quimioterapia); e 3) Medidas específicas focais (que tratam somente os focos macroscópicos da doença cerebral, como radiocirurgia estereotáxica e neurocirurgia). Embora o aparecimento de metástases cerebrais represente uma situação clínicadramaticamente negativa, a crença que associa o diagnóstico desta entidade com uma sentença de morte iminente deve ser revista, pois dependendo dos fatores prognósticos associados, certamente a sobrevida dos pacientes pode variar desde semanas até anos. Esta revisão tem foco de discussão na influência que a correta valorização de possíveis fatores prognósticos pode exercer na escolha adequada da terapia para pacientes com metástases cerebrais, no sentido de maximizar benefícios, em termos de qualidade e tempo de sobrevida. A observação dos fatores prognósticos na avaliação do tratamento de metástases cerebrais, certamente uma forma de estadiamento desta entidade, pode ser um importante aliado do paciente na busca de algo além da mera paliação de sua doença.

Can anticancer chemotherapy promote the progression of brain metastases?

Brain metastases natural history from one primary tumor type might be accelerated or favored by using certain systemic chemotherapy. A great deal was described in mice and suggested in human with antiangiogenic drugs, but little is known about the metastatic progression generated by the perverse effect of anticancer drugs. A total of 413 patients who underwent treatment for brain metastasis (2013-2016) were included. The identification of all previous anticancer drugs received by patients from primary tumor diagnosis to brain metastases diagnosis was collated. The median value for the time of first appearance of brain metastasis in all patients was 13.1months (SD 1.77). The values of brain metastasis-free survival (bMFS) for each primary cancer were: 50.9months (SD 8.8) for breast, 28.5months (SD 11.4) for digestive, 27.7months (SD 18.3) for melanoma, 12.3months (SD 8.3) for kidney, 1.5months (SD 0.1) for lung and 26.9months (SD 18.3) for others (p<0.009). Through Cox multivariate proportional hazard model, we identified that the only independent factors associated with short bMFS were: lung primary tumor [odd ratio (OR) 0.234, CI 95% 0.16-0.42; p<0.0001] and mitotic spindle inhibitor (taxanes) chemotherapy [OR 0.609, CI 95% 0.50-0.93; p<0.001]. Contrariwise, breast primary tumor [odd ratio (OR) 2.372, CI 95% 1.29-4.3; p<0.005] was an independent factor that proved a significantly longer bMFS. We suggest that anticancer drugs, especially taxane and its derivatives, could promote brain metastases, decreasing free survival. Mechanisms are discussed but still need to be determined.

The problem of current classications of the hepatocellular carcinoma. Analytical review

Hepatocellular carcinoma (HCC) in vast majority of cases develops on the background of the chronic liver diseases, more often – viral hepatitis B and C, and is diagnosed at the advanced stages [1, 3]. Despite the advantages of the modern oncology (some patients live till appearance of brain metastases [1]), prognosis in HCC is still poor. In general, prognosis depends on not only biological characteristics of the tumor itself, but also on the background of the liver condition, often – at the stage of the cirrhosis. As distinct from the other malignant tumor of liver – cholangiocellular carcinoma, there are no universal prognostic classifications for HCC [2]. International classification TNM used for majority of solid tumors is not appropriate to be ‘reference’ for HCC [4]. There are several prognostic scales and classifications created recently in West and Asian countries. For the creation of such systems they use more often the regression model on the basis of prognostic variables of the investigated population. Currently, there is no universal prognostic classification or scale for HCC ГЦР. Almost all these classifications included the features; liver function, tumor characteristics, clinical behavior, undercurrent diseases, presence of the cirrhosis [3].

脳転移巣の出現から7年後に顕在化した潜在性肺癌の1例

脳転移巣の出現から7年後に顕在化した潜在性肺癌の1例

Abstract 3140: Differential clonal selection in tumor tissue and cell-free DNA from a neratinib-treated refractory breast cancer patient harboring an activating ERBB2 (HER2) mutation

Abstract The ongoing Copenhagen Prospective Personalized Oncology (CoPPO) research program aims to offer patients with exhausted treatment options, targeted therapy against actionable driver mutations identified in freshly obtained biopsies by whole exome sequencing (WES). Mutations are tracked in circulating cell free DNA (cfDNA) to examine the clonal selection of tumor cells evoked by therapy. Here we report the results from a patient with metastasizing HER2 negative and estrogen receptor (ER) positive breast cancer (Luminal A) previously exposed to seven lines of chemotherapy as well as ER antagonists and aromatase inhibitors. After enrollment in the program, examination of liver metastases by whole exome sequencing, RNA-Seq and microarray expression analysis revealed high expression of the estrogen receptor 1 (ESR1) as well as a mutation in the ligand-binding domain of ESR1 (H524L). Moreover, somatic variants in ERBB2 and PIK3CA were identified, including an activating mutation in ERBB2 (S310Y), and consequently the patient treated with neratinib, an irreversible pan-HER (EGFR/ERBB2/ERBB4) tyrosine kinase inhibitor, through a compassionate use program (Puma Biotechnology Inc.). Neratinib caused a rapid decrease in the allelic frequency of ERBB2 (S310Y) cfDNA after 2 days with a continuous decline during the next 7 days. Consistent with this neratinib treatment effect, MRI scans showed regression of the liver metastases. In contrast, the PIK3CA mutation showed an increase in the allele frequency, indicating the existence of a subclone that was insensitive to neratinib. Two months later, the total amount of cfDNA increased and continued to do so. After 5 months on neratinib, the patient progressed with the appearance of brain metastases which were surgically removed and subject to WES. The vast majority of the mutations, including the ERBB2 mutation, observed in the liver metastasis could not be identified in the brain metastases, except for the PIK3CA mutation. More than 300 new variants were exclusively identified in the brain metastases, among these, ERBB3 as well as new PIK3CA, and ESR1 mutations, that were not present in the pre-treatment cfDNA samples. After 4 months of treatment, an increase in the mutation frequency of the liver metastasis specific ESR1 and ERBB2 mutations was observed. In conclusion, neratinib was able to suppress an activating ERBB2 mutation in a heavily pre-treated ER+ breast cancer patient. However, refractory tumor clones harboring ERBB3, PIK3CA and ESR1 mutations developed in brain. These data indicate that combining neratinib with fulvestrant or inhibitors of the HER3/PI3K/AKT/mTOR pathway might prove beneficial to overcome potential resistance mechanisms to therapy. The two first authors contributed equally. Citation Format: Lars Joenson, Christina W. Yde, Olga Østrup, Morten Mau-Sørensen, Finn C. Nielsen, Ulrik Lassen. Differential clonal selection in tumor tissue and cell-free DNA from a neratinib-treated refractory breast cancer patient harboring an activating ERBB2 (HER2) mutation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3140.

P2-003 - Retrospective Study of Prophylactic Cranial Irradiation in Small-Cell Lung Cancer: Neurocognitive Analysis

ABSTRACT Background PCI has been established as the standard therapy for SCLC. The concerns of severe late neurotoxicity and detrimental impact on the QOL of patients undergoing PCI have been reported but never seriously studied. We therefore studied the neurocognitive functioning (NCF) of small-cell lung cancer cases treated with PCI in our institution. Patients and methods We retrospectively analyzed small-cell lung cancer cases treated with PCI atour hospital between 2004 and 2011. NCF was assessed using the Mini-Mental Status Examination (MMSE). The median follow-up time for all patients was 25 months (range, 4–85 months). Results Seventeen small-cell lung cancer cases treated with PCI were identified. Their median age was 66 years (range, 52–78 years). Brain metastases after PCI occurred in six patients (35%). Dementia occurred in five patients (29%, 3–40 months after PCI) without or before appearance of brain metastases. The median age of patients with dementia was 75 years (range, 68–78 years). Gait disturbance appeared in three patients (18%, 9–27 months after PCI). Conclusion The impact of PCI on NCF needs to be considered, especially in older patients. We should consider the risk and the beneficial effects of PCI on survival and incidence of brain metastases.

Chemotherapy response assessment in stage IV melanoma patients—comparison of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B

This study aims to compare the use of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B in chemotherapy response assessment of stage IV melanoma patients. In 25 patients with stage IV melanoma, FDG-PET/CT and S-100B after 2-3 months (three cycles) of chemotherapy was compared with baseline PET/CT and baseline S-100B. Retrospectively, the response was correlated with the outcome. In patients with clinical suspicion for brain metastases, MRI or CCT was performed. There was agreement between FDG-PET/CT and CT regarding response to chemotherapy in all patients. There was a clear trend to a longer OS of PET/CT responders (n=10) compared with PET/CT non-responders (n=15; p=0.072) with remarkably better 1-year OS of 80% compared to 40% (p=0.048). There was a significant longer PFS of PET/CT responders compared with PET/CT non-responders (p=0.002). S-100B was normal at baseline in eight of 22 patients where it was available. Chemotherapy response assessment with S-100B failed to show correlation with OS or PFS. Eleven patients developed brain metastases during treatment, first detected by PET/CT in two and by MRI or CCT in nine of 11 patients. Appearance of brain metastases was associated with a poor survival. 18F-FDG-PET/CT and CT alone are equally suitable for chemotherapy response assessment in melanoma patients and clearly superior to S-100B. PET/CT responders have better early survival, but this is shortlived due to late therapy failure--often with brain recurrence. Additional brain MRI for therapy response assessment in such high-risk patients is mandatory to detect brain metastases missed by PET/CT.

Factors affecting the prognosis of breast cancer patients with brain metastases

The aim of this retrospective analysis was to investigate the factors affecting the prognosis of brain metastases in breast cancer patients to identify subgroups which might benefit from prophylactic treatments in future. Seventy-three early and 13 advanced stage patients with known Erb-2 status were included. In 14% of the early stage patients, the first recurrence site was isolated brain metastasis. None of the anthracycline resistant patients had brain metastases as their first recurrence site. The median interval between diagnosis and brain metastasis was 41.5 months (95% CI, 35.79–47.20) in early stage patients. The median interval between the first extracerebral metastases to the brain metastases was 15.5 months (95% CI, 12.24–18.76) in all patients. High histologic and nuclear grade, large tumor, anthracycline resistance were the factors which significantly affected the early appearance of brain metastases but only advanced age (≥55 years, P = .035) correlated with isolated brain metastasis. Progression with isolated brain metastases was significantly higher in responsive ErbB-2 positive population ( P = .036) and none of other pathological factors was associated with isolated brain metastasis in advanced stage. The median survival after brain metastasis in patients with brain metastasis as first recurrence was longer than the patients with brain metastasis after other organ metastasis (13 months vs 2 months P = .003). The median survival following brain metastases in complete responsive patients was higher than the others (24 months vs 6 months, P = .002). Therefore, response to systemic treatment was more determinative in the development of isolated brain metastases than clinical and pathologic features. ErbB-2 should be emphasized in prophylactic treatment strategies. Prophylactic cranial radiotherapy may be an effective treatment option for metastatic patients with complete responsive disease and with controlled ErbB-2 positive disease.

Headache characteristics and brain metastases prediction in cancer patients

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 > or =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.