Brain and Spinal Cord Tumours
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Information for Patients and the Public
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Latest Research Publications
Childhood Brain Tumours
Pituitary Tumours
Primary CNS Lymphoma
Acoustic Neuroma
Neuro-oncology (specialty)

Information Patients and the Public (15 links)

Information for Health Professionals / Researchers (24 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Friedmann-Morvinski D
Glioblastoma heterogeneity and cancer cell plasticity.
Crit Rev Oncog. 2014; 19(5):327-36 [PubMed] Related Publications
Glioblastoma (GBM) is the most common and malignant type of primary brain tumor. It represents one of the deadliest human cancers, with an average survival at diagnosis of about 1 year. This poor prognosis is due to therapeutic resistance and tumor recurrence after surgical removal. One of the most important hallmarks of GBM is tumor heterogeneity. Intertumor heterogeneity is mostly characterized by distinct genetic alterations that occur in individual tumors originating in the same organ and allows the classification of these tumors into different molecular subtypes. Intratumor heterogeneity-the diversity within individual tumors-has become the focus of research interest in the past few years, and tumor cell plasticity as a new source of cancer stem cells has added another level of complexity to this phenomenon. This review describes the molecular heterogeneity of GBMs at the transcriptome level and the expression profile-based classification of histopathologically indistinguishable tumors into different subtypes. In addition, the role of dedifferentiation of tumor cells into a stem cell-like state is discussed as a source of cellular heterogeneity within tumors, highlighting tumor cell plasticity as an important driver of GBM heterogeneity. Understanding tumor heterogeneity will help design better therapies against GBM and avoid tumor recurrence.

Rades D, Dziggel L, Bartscht T, Gliemroth J
Predicting overall survival in patients with brain metastases from esophageal cancer.
Anticancer Res. 2014; 34(11):6763-5 [PubMed] Related Publications
AIM: To identify survival predictors and develop a survival score for patients with brain metastases from esophageal cancer.
PATIENTS AND METHODS: In 16 patients, seven factors were analyzed including age, gender, Karnofsky performance score (KPS), time from diagnosis of esophageal cancer to irradiation, number of brain metastases, histology, and presence of extracerebral metastases.
RESULTS: Improved survival was significantly associated with KPS≥80 (p<0.001), the presence of one brain metastasis (p=0.007), and no extra-cerebral metastases (p=0.002). These factors were included in the final score. Factor scores were calculated by dividing 6-month survival rates by 10. Total survival scores represented the sums of factor scores and were 2, 7, 10, 19 or 24 points. Six-month survival rates by score were 0%, 0%, 0%, 67% and 100%, respectively. Two groups were formed, those of patients with 2-10 points and those with 19-24 points; 6-month survival was 0% and 88%, respectively (p<0.001).
CONCLUSION: This new score facilitates the selection of individual therapies for patients with brain metastases from esophageal cancer.

Related: Cancer of the Esophagus Esophageal Cancer

Nieder C, Angelo K, Haukland E, Pawinski A
Survival after palliative radiotherapy in geriatric cancer patients.
Anticancer Res. 2014; 34(11):6641-5 [PubMed] Related Publications
BACKGROUND/AIM: Older cancer patients might experience inferior survival outcomes. However, no standard age cut-off is currently being used for commonly administered treatments such as radiotherapy. We evaluated survival outcomes and prognostic factors for survival after palliative radiotherapy (PRT) in our oldest patients (age≥80 years).
PATIENTS AND METHODS: This retrospective study covered the time period between 2007 and 2012, and included 94 patients in this age group who were treated with PRT. Comparisons to a group of younger patients (31-79 years of age, N=445) treated during the same time period were made. Uni- and multivariate analyses were also performed. Most patients received PRT for bone and brain metastases or in order to improve thoracic symptoms from lung cancer.
RESULTS: Median age was 83 years. Survival outcomes and rates of PRT completion were not significantly different. Short median survival of less than 2 months was observed in two sub-groups of geriatric patients; those with brain metastases and those with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 4. Multivariate analysis confirmed the prognostic impact of PS, adrenal gland metastases, progressive disease outside PRT target volume(s), need for opioid analgetics and steroids (all p<0.05). Brain metastasis was associated with a borderline increase in risk of mortality (p=0.051).
CONCLUSION: Our data support utilization of PRT irrespective of age for most patients with PS 0-3 but care should be taken in selecting the right fractionation regimen in order to avoid lengthy PRT courses when survival is limited.

Related: Cancer Prevention and Risk Reduction

Jarząb A, Grabarska A, Kiełbus M, et al.
Osthole induces apoptosis, suppresses cell-cycle progression and proliferation of cancer cells.
Anticancer Res. 2014; 34(11):6473-80 [PubMed] Related Publications
BACKGROUND: The aim of the present study was to determine the effects of osthole on cell proliferation and viability, cell-cycle progression and induction of apoptosis in human laryngeal cancer RK33 and human medulloblastoma TE671 cell lines.
MATERIALS AND METHODS: Cell viability was measured by means of the MTT method and cell proliferation by the 5-bromo-2-deoxyuridine (BrdU) incorporation assay. Cell-cycle progression was determined by flow cytometry, and induction of apoptosis by release of oligonucleosomes to the cytosol. The gene expression was estimated by a quantitative polymerase chain reaction (qPCR) method. High-performance counter-current chromatography (HPCCC) was applied for isolation of osthole from fruits of Mutellina purpurea.
RESULTS: Osthole decreased proliferation and cell viability of cancer cells in a dose-dependent manner. The tested compound induced apoptosis, increased the cell numbers in G1 and decreased cell number in S/G2 phases of the cell cycle, differentially regulating CDKN1A and TP53 gene expression depending on cancer cell type.
CONCLUSION: Osthole could be considered as a potential compound for cancer therapy and chemoprevention.

Related: Apoptosis CDKN1A Cancer of the Larynx Laryngeal Cancer - Molecular Biology Childhood Medulloblastoma / PNET TP53

Branch BC, Henry J, Vecil GG
Brain metastases from cervical cancer--a short review.
Tumori. 2014 Sep-Oct; 100(5):e171-9 [PubMed] Related Publications
AIMS AND BACKGROUND: Brain metastases from cervical cancer are extremely rare yet local recurrence and systemic spread is fairly common. The role of surgical resection and CNS screening for this pathology was interrogated from a review of the literature.
CLINICAL EXPERIENCE: We present a case of a single brain metastasis that originated from the cervix and describe chronologically the spread of the disease with pathological confirmations.
REVIEW: Following an extensive English literature search, which only yielded 59 reported cases (n = 60 including the present case), we extrapolated basic trends regarding the demographics, pathophysiology, and treatment that portended a longer survival. Despite treatment, the majority of patients do not survive past 1 year from diagnosis of intracranial metastasis. A trend towards prolonged survival was observed among patients who received surgical resection of the brain metastasis.
CONCLUSIONS: Cervical carcinoma has been documented to metastasize to the brain, and this may occur via initial seeding of the lungs. Surgical resection and CNS screening may have beneficial roles in the management of metastatic cervical carcinoma.

Related: Cervical Cancer

Traşcă D, Şerban AS, Ştefănescu V, et al.
Meningeal carcinomatosis in a patient with Crohn's disease.
Rom J Intern Med. 2014 Apr-Jun; 52(2):111-20 [PubMed] Related Publications
Leptomeningeal carcinomatosis, also known as carcinomatous meningitis, is defined by spreading of neoplastic cells to the meninges and ventricles, and is a form of cancer dissemination. In this case, a patient with inflammatory bowel disease had developed a neoplastic process that spread to the meninges. A 49-year-old woman developed an abdominal pain, and was diagnosed the same month with Crohn's disease, complicated with intestinal perforation, for which she was hospitalized. Pathological examination revealed acute phase-terminal ileitis. She undergone many hospitalizations during which she was suspected to have celiac disease, inflammatory bowel disease, and tuberculous meningitis, as well as femoral head necrosis after she had been unsuccessfully treated with Prednisone for Crohn's disease. After she developed peripheral bilateral facial paresis, bilateral hypoacusia, hypotonia, tetraparesis and diminished osteotendinous reflexes at the legs, the patient was admitted in our department. Several lumbar punctures were performed but no specific disease could be detected. The MRI performed showed pachymeningeal and leptomeningeal inflammation. Tuberculous meningitis was taken into consideration and the patient was transferred into an Infectious Disease Department where this diagnostic was infirmed. The patient was retransferred into the Department of Neurology where after an episode of hematemesis she had a cardiac arrest and deceased. Inflammatory bowel disease may involve different segments of the intestine, and may be accompanied by a variety of conditions, such as neurologic findings, osteoarticular manifestations and also may be the starting point of a neoplastic process. The patient had an inflammatory bowel condition, which by the time it was appropriately diagnosed as being Crohn's disease, a neoplastic process spread to the meninges, causing multiple cranial nerve palsy, tetraparesis, along other neurological manifestations.

Kwon D, Shinohara RT, Akbari H, Davatzikos C
Combining generative models for multifocal glioma segmentation and registration.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 1):763-70 [PubMed] Free Access to Full Article Related Publications
In this paper, we propose a new method for simultaneously segmenting brain scans of glioma patients and registering these scans to a normal atlas. Performing joint segmentation and registration for brain tumors is very challenging when tumors include multifocal masses and have complex shapes with heterogeneous textures. Our approach grows tumors for each mass from multiple seed points using a tumor growth model and modifies a normal atlas into one with tumors and edema using the combined results of grown tumors. We also generate a tumor shape prior via the random walk with restart, utilizing multiple tumor seeds as initial foreground information. We then incorporate this shape prior into an EM framework which estimates the mapping between the modified atlas and the scans, posteriors for each tissue labels, and the tumor growth model parameters. We apply our method to the BRATS 2013 leaderboard dataset to evaluate segmentation performance. Our method shows the best performance among all participants.

Meier R, Bauer S, Slotboom J, et al.
Patient-specific semi-supervised learning for postoperative brain tumor segmentation.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 1):714-21 [PubMed] Related Publications
In contrast to preoperative brain tumor segmentation, the problem of postoperative brain tumor segmentation has been rarely approached so far. We present a fully-automatic segmentation method using multimodal magnetic resonance image data and patient-specific semi-supervised learning. The idea behind our semi-supervised approach is to effectively fuse information from both pre- and postoperative image data of the same patient to improve segmentation of the postoperative image. We pose image segmentation as a classification problem and solve it by adopting a semi-supervised decision forest. The method is evaluated on a cohort of 10 high-grade glioma patients, with segmentation performance and computation time comparable or superior to a state-of-the-art brain tumor segmentation method. Moreover, our results confirm that the inclusion of preoperative MR images lead to a better performance regarding postoperative brain tumor segmentation.

Weibel HS, Dahan MH
Pituitary mass and subsequent involution causing fluctuations of serum follicle-stimulating hormone levels in a Turner syndrome patient with premature ovarian failure: a case report.
J Reprod Med. 2014 Sep-Oct; 59(9-10):504-8 [PubMed] Related Publications
BACKGROUND: Premature ovarian failure (POF) is described as estrogen deficiency, amenorrhea, and hypergonadotropinemia in a woman < 40 years old. In a proportion of patients diagnosed with POF, intermittent and unpredictable return of ovarian function can be observed, causing fluctuations of follicle-stimulating hormone (FSH). However, these patients also have return of menstrual cycles. When cycles do not resume, other causes could explain the changes in FSH levels.
CASE: A 43-year-old woman with known premature ovarian failure since age 23 and high serum FSH levels was referred for normalization of FSH levels. She did not have any resumption of menstrual cycles. Karyotype revealed a mosaicism consistent with Turner syndrome. Computed tomography of the head detected a pituitary macroadenoma which is believed to have caused a decrease in FSH production by compression of the pituitary stalk. Spontaneous involution of the mass ensued, and the patient's serum FSH returned to menopausal level accompanied by an empty sella syndrome.
CONCLUSION: In menopausal patients with low FSH and no return of menstrual cycles, further investigations should be pursued in order to exclude a possible pituitary mass.

Related: Pituitary Tumors

Liu X, Niethammer M, Kwitt R, et al.
Low-rank to the rescue - atlas-based analyses in the presence of pathologies.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 3):97-104 [PubMed] Related Publications
Low-rank image decomposition has the potential to address a broad range of challenges that routinely occur in clinical practice. Its novelty and utility in the context of atlas-based analysis stems from its ability to handle images containing large pathologies and large deformations. Potential applications include atlas-based tissue segmentation and unbiased atlas building from data containing pathologies. In this paper we present atlas-based tissue segmentation of MRI from patients with large pathologies. Specifically, a healthy brain atlas is registered with the low-rank components from the input MRIs, the low-rank components are then re-computed based on those registrations, and the process is then iteratively repeated. Preliminary evaluations are conducted using the brain tumor segmentation challenge data (BRATS '12).

Prasanna P, Tiwari P, Madabhushi A
Co-occurrence of local anisotropic gradient orientations (CoLIAGe): distinguishing tumor confounders and molecular subtypes on MRI.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 3):73-80 [PubMed] Related Publications
We introduce a novel biologically inspired feature descriptor, Co-occurrence of Local Anisotropic Gradient Orientations (CoLlAGe), that captures higher order co-occurrence patterns of local gradient tensors at a pixel level to distinguish disease phenotypes that have similar morphologic appearances. A number of pathologies (e.g. subtypes of breast cancer) have different histologic phenotypes but similar radiographic appearances. While texture features have been previously employed for distinguishing subtly different pathologies, they attempt to capture differences in global intensity patterns. In this paper we attempt to model CoLlAGe to identify higher order co-occurrence patterns of gradient tensors at a pixel level. The assumption behind this new feature is that different pathologies, even though they may have very similar overall texture and appearance on imaging, at a local scale, will have different co-occurring patterns with respect to gradient orientations. We demonstrate the utility of CoLIAGe in distinguishing two subtly different types of pathologies on MRI in the context of brain tumors and breast cancer. In the first problem, we look at CoLlAGe for distinguishing radiation effects from recurrent brain tumors over a cohort of 40 studies, and in the second, discriminating different molecular subtypes of breast cancer over a cohort of 73 studies. For both these challenging cohorts, CoLlAGe was found to have significantly improved classification performance, as compared to the traditional texture features such as Haralick, Gabor, local binary patterns, and histogram of gradients.

Related: Breast Cancer

Lauth M, Toftgard R
Think inside the BOCs: a mechanism underlying medulloblastoma progression.
Dev Cell. 2014; 31(1):1-2 [PubMed] Related Publications
Approximately one-third of medulloblastoma cases are associated with genetic lesions of Hedgehog (Hh) signaling pathway components. In this issue of Developmental Cell, Mille et al. (2014) show that the Hh coreceptor Boc functions specifically in the progression of early- to advanced-stage medulloblastoma by promoting Cyclin D1-dependent DNA damage and genomic instability.

Related: Childhood Medulloblastoma / PNET

Piccirilli M, Maiola V, Salvati M, et al.
Granular cell tumor of the neurohypophysis: a single-institution experience.
Tumori. 2014 Jul-Aug; 100(4):160e-4e [PubMed] Related Publications
Granular cell tumor (GCT) is a rare neoplasm occurring in the sellar and suprasellar spaces. It is a primary tumor of the neurohypophysis, presumably arising from the pituicytes, a distinctive glial cell of the neurohypophysis. GCTs in most reported cases show biologically benign behavior with slow growth. Only 70 cases of hypophyseal GCTs have been reported in the literature. We report a case of GCT in the neurohypophysis of a 46-year-old woman and discuss the histological and clinical features of this neoplasm together with the treatment modalities, reviewing the pertinent literature.

Related: Pituitary Tumors

Ganau M, Foroni RI, Gerosa M, et al.
Radiosurgical options in neuro-oncology: a review on current tenets and future opportunities. Part I: therapeutic strategies.
Tumori. 2014 Jul-Aug; 100(4):459-65 [PubMed] Related Publications
Stereotactic radiosurgery can nowadays be considered not only as a potential adjuvant to surgical treatment of several neuro-oncological pathologies, including primary tumors and metastatic lesions, but in some cases also as a valuable alternative tailored option. In Part I of the review, we propose a dissertation focused on the different irradiation stereotactic radiosurgery techniques to date available for clinical indications more relevant to oncologists and oncologic surgeons, such as high-grade and low-grade gliomas, metastases and meningiomas. It is noteworthy that the most recent body of literature correlated with this topic shows that the therapeutic results presently achievable are revolutionizing the way patients are diagnosed and managed worldwide. As we sought to shed light on the current potentialities of stereotactic radiosurgery, we must consider that to exploit all the benefits provided by this shift in clinical practice, a profound awareness by all practitioners involved in the care of neoplastic patients is certainly warranted.

Ojha SS, Naik LP, Kothari KS, et al.
Amyloid goiter: cytomorphological features and differential diagnosis on fine needle aspiration cytology: a case report.
Anal Quant Cytopathol Histpathol. 2014; 36(4):241-4 [PubMed] Related Publications
BACKGROUND: Amyloid goiter is a rare cause of thyroid enlargement which can be confused clinically as well as cytologically with both colloid goiter and neoplastic process of thyroid.
CASE: A 30-year-old man, diagnosed with chronic kidney disease 5 months previously and currently on dialysis and awaiting renal transplant, was referred by clinicians for fine needle aspiration cytology (FNAC) for thyroid swelling. FNAC showed dense amorphous clumps of extracellular material which appeared magenta colored on Giemsa and eosinophilic on Papanicolaou stain. Congo red staining and polarization showed characteristic apple green birefringence, thus confirming the material as amyloid, and the diagnosis of amyloid goiter was made.
CONCLUSION: Amyloid on FNAC smears can be easily mistaken for colloid, and correct interpretation can avoid a false diagnosis of colloid goiter. A search should be made to look for any features suggestive of medullary carcinoma of the thyroid as amyloid is more often associated with it.

Solomon IH, Ramkissoon SH, Milner DA, Folkerth RD
Cytomegalovirus and glioblastoma: a review of evidence for their association and indications for testing and treatment.
J Neuropathol Exp Neurol. 2014; 73(11):994-8 [PubMed] Related Publications
Glioblastoma is the most common and most fatal primary malignant brain tumor in adults. Despite progress in characterizing the genetic and molecular mechanisms of glioblastomas, advances in treatment that translate into substantial improvement in prognosis have yet to be realized. A role for cytomegalovirus in glioblastoma pathogenesis was proposed more than a decade ago and has generated considerable debate as a possible therapeutic target. Independent groups have had variable success in detecting cytomegalovirus infection in tumor cells; the overall consensus is that very low levels of viral proteins and nucleic acids can be observed. Although cytomegalovirus has not been found to be oncogenic in this context, a possible oncomodulatory role has been suggested. A recent clinical trial evaluating valganciclovir as an adjuvant therapy for the treatment of glioblastoma did not demonstrate a beneficial effect on tumor growth or overall survival, although retrospective analysis subsequently indicted a significant survival benefit. In light of the publicity of that report, patients and neuro-oncologists are requesting cytomegalovirus testing to justify antiviral treatment. Based on questions on the significance of cytomegalovirus infection in glioblastomas and the lack of a clear clinical benefit of valganciclovir, we reviewed this topic and conclude that, at this time, there is insufficient evidence to recommend routine testing and treatment.

Koschny R, Boehm C, Sprick MR, et al.
Bortezomib sensitizes primary meningioma cells to TRAIL-induced apoptosis by enhancing formation of the death-inducing signaling complex.
J Neuropathol Exp Neurol. 2014; 73(11):1034-46 [PubMed] Related Publications
A meningioma is the most common primary intracranial tumor in adults. Here, we investigated the therapeutic potential of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in 37 meningiomas. Freshly isolated primary meningioma cells were treated with TRAIL with or without different sensitizing protocols, and apoptotic cell death was then quantified. Mechanisms of TRAIL sensitization were determined by a combination of Western blotting, flow cytometry, receptor complex immunoprecipitation, and siRNA-mediated knockdown experiments. Tumor necrosis factor-related apoptosis-inducing ligand receptor expression was analyzed using immunohistochemistry and quantified by an automated software-based algorithm. Primary tumor cells from 11 (29.7%) tumor samples were sensitive to TRAIL-induced apoptosis, 12 (32.4%) were intermediate TRAIL resistant, and 14 (37.8%) were completely TRAIL resistant. We tested synergistic apoptosis-inducing cotreatment strategies and determined that only the proteasome inhibitor bortezomib potently enhanced expression of the TRAIL receptors TRAIL-R1 and/or TRAIL-R2, the formation of the TRAIL death-inducing signaling complex, and activation of caspases; this treatment resulted in sensitization of all TRAIL-resistant meningioma samples to TRAIL-induced apoptosis. Bortezomib pretreatment induced NOXA expression and downregulated c-FLIP, neither of which caused the TRAIL-sensitizing effect. Native TRAIL receptor expression could not predict primary TRAIL sensitivity. This first report on TRAIL sensitivity of primary meningioma cells demonstrates that TRAIL/bortezomib cotreatment may represent a novel therapeutic option for meningiomas.

Related: Apoptosis TNFSF10 Bortezomib

Xiong A, Kundu S, Forsberg-Nilsson K
Heparan sulfate in the regulation of neural differentiation and glioma development.
FEBS J. 2014; 281(22):4993-5008 [PubMed] Related Publications
Heparan sulfate proteoglycans (HSPGs) are the main components of the extracellular matrix, where they interact with a large number of physiologically important macromolecules. The sulfation pattern of heparan sulfate (HS) chains determines the interaction potential of the proteoglycans. Enzymes of the biosynthetic and degradation pathways for HS chains are thus important regulators in processes ranging from embryonic development to tissue homeostasis, but also for tumor development. Formation of the nervous system is also critically dependent on intact HSPGs, and several studies have outlined the role of HS in neural induction from embryonic stem cells. High-grade glioma is the most common malignant primary brain tumor among adults, and the outcome is poor. Neural stem cells and glioma stem cells have several common traits, such as sustained proliferation and a highly efficient migratory capacity in the brain. There are also similarities between the neurogenic niche where adult neural stem cells reside, and the tumorigenic niche. These include interactions with the extracellular matrix, and many of the matrix components are deregulated in glioma, e.g. HSPGs and enzymes implementing the biosynthesis and modification of HS. In this article, we will present how HS-regulated pathways are involved in neural differentiation, and discuss their impact on brain development. We will also review and critically discuss the important role of structural modifications of HS in glioma growth and invasion. We propose that targeting invasive mechanisms of glioma cells through modulation of HS structure and HS-mediated pathways may be an attractive alternative to other therapeutic attempts, which so far have only marginally increased survival for glioma patients.

Related: Angiogenesis and Cancer Signal Transduction

Joo JH, Park JH, Ra YS, et al.
Treatment outcome of radiation therapy for intracranial germinoma: adaptive radiation field in relation to response to chemotherapy.
Anticancer Res. 2014; 34(10):5715-21 [PubMed] Related Publications
AIM: To determine the optimal radiotherapy (RT) target volume in correlation with tumor response to chemotherapy in patients with intracranial germinoma.
PATIENTS AND METHODS: Seventy-two patients received chemotherapy followed by RT. The RT field was tailored to chemotherapy response.
RESULTS: Five-year recurrence-free survival (RFS) was 87% and overall survival was 97%. RT field was significantly associated with RFS, with 5-year RFS rates of 95%, 91%, and 62% in those who received craniospinal irradiation, whole-brain/whole-ventricle RT, and focal RT, respectively (p=0.01). In the complete-response group after chemotherapy, 5-year RFS rates were 100% after whole-brain RT/whole-ventricle RT and 70% after focal RT (p=0.04). In the partial-response group, 5-year RFS rates after craniospinal irradiation, whole-brain RT, and focal RT were 100%, 85%, and 33%, respectively (p<0.01).
CONCLUSION: Regardless of response, those treated with focal RT had an excessively high relapse rate. Whole-brain/whole-ventricle RT could be applied to patients who show a complete response to chemotherapy, but the optimal strategy for patients with partial response needs further investigation.

Related: Childhood Brain Tumours Childhood Brain Tumors

Fábián K, Németh Z, Furák J, et al.
Protein expression differences between lung adenocarcinoma and squamous cell carcinoma with brain metastasis.
Anticancer Res. 2014; 34(10):5593-7 [PubMed] Related Publications
AIM: We investigated tissue biomarkers in non-small cell lung cancer (NSCLC) to find indicators of brain metastasis and peritumoral brain edema.
PATIENTS AND METHODS: Fifty-two cases were studied out of which 26 had corresponding brain metastatic tissue. Clinicopathological characteristics of tumors were correlated with biomarkers of cell adhesion, cell growth, cell cycle and apoptosis regulation that were previously immunohistochemically studied but never analyzed separately according to histological subgroups, gender and smoking history.
RESULTS: Increased collagen XVII in adenocarcinoma (ADC) and increased caspase-9, CD44v6, and decreased cellular apoptosis susceptibility protein (CAS) and Ki-67 in squamous cell carcinoma (SCC) correlated significantly with brain metastasis. Increased β-catenin, E-cadherin and decreased caspase-9 expression in primary SCC, and decreased CD44v6 expression in brain metastatic SCC tissues showed a significant correlation with the extent of peritumoral brain edema. Positive correlation between smoking and biomarker expression could be observed in metastatic ADCs with p16 and caspase-8, while-negative correlation was found in SCC without brain metastasis with caspase-3, and in SCC with brain metastasis with p27.
CONCLUSION: Our results highlight the importance of separate analysis of biomarker expression in histological subtypes of NSCLC.

Related: Lung Cancer

Huttenlocher S, Sehmisch L, Schild SE, et al.
Identifying melanoma patients with 1-3 brain metastases who may benefit from whole-brain irradiation in addition to radiosurgery.
Anticancer Res. 2014; 34(10):5589-92 [PubMed] Related Publications
BACKGROUND/AIM: To develop a tool for estimating the risk of developing new cerebral lesions in 69 melanoma patients receiving radiosurgery for 1-3 cerebral metastases.
PATIENTS AND METHODS: Ten factors were investigated: lactate dehydrogenase (LDH), radiosurgery dose, age, gender, performance status, maximum diameter, location and number of cerebral lesions, extra-cranial spread, time between melanoma diagnosis and radiosurgery. Two factors, number of lesions and extra-cranial spread, were included in the tool. Scoring points were achieved by dividing the 6-month rate of freedom from new cerebral lesions by 10.
RESULTS: Sum scores were 9, 11, 12 or 14 points. Six-month rates of freedom from new brain metastases were 28%, 63%, 59% and 92% (p=0.002). Three prognostic groups were designed: A (9 points), B (11-12 points) and C (14 points). Freedom from new cerebral lesion rates were 28%, 60% and 92% (p<0.001).
CONCLUSION: Group A and B patients should be considered for additional whole-brain radiotherapy (WBRT).

Related: Melanoma

Bălinişteanu B, Cimpean AM, Melnic E, et al.
Crosstalk between tumor blood vessels heterogeneity and hormonal profile of pituitary adenomas: evidence and controversies.
Anticancer Res. 2014; 34(10):5413-20 [PubMed] Related Publications
AIM: Pituitary adenomas are intracranial tumors with controversial histopathology and heterogeneous clinical behaviour. Angiogenesis and tumor blood vessels' role in pathogenesis, remain one of the great pituitary tumor mysteries. No connection between tumor vessel heterogeneity, hormonal profile and biological behaviour has been reported. We aimed to study pituitary adenomas blood vessels concerning their immature, intermediate or mature phenotype and microvessel density, correlated with immunohistochemical hormonal profile and hormone values in serum and cerebrospinal fluid.
MATERIALS AND METHODS: We classified pituitary adenomas according to hormone profile and we applied a double immunostaining highlighting both endothelial and perivascular cells for a more accurate assessment of blood vessel types.
RESULTS: Overall microvessel density was found to be highest in growth hormone-secreting adenomas (48.51 ± 12.15) and lowest in prolactinomas (29.15 ± 18.78). When we differentially counted tumor blood vessels we observed a predominance of immature and intermediate blood vessels compared to mature ones. A significant correlation was found between immature tumor blood vessels and tissue prolactin expression, as assessed by immunhistochemistry (p=0.044). A partial correlation was found between serum (p=0.036) and cerebrospinal prolactin values (p=0.006) with immature and intermediate blood vessels. Also, a partial correlation has been reported only between mature blood vessels and cerebrospinal fluid prolactin values (p=0.008). No correlation was obtained for other types of pituitary adenomas.
CONCLUSION: Our results suggest a strong involvement of prolactin with a dual role in pituitary adenomas vasculature remodelling by acting both on endothelial and perivascular cells, a finding that could partially explain discrepancies between clinical diagnosis and hormonal profile.

Related: Angiogenesis and Cancer Pituitary Tumors

Ceresa C, Nicolini G, Semperboni S, et al.
Synchrotron-based photon activation therapy effect on cisplatin pre-treated human glioma stem cells.
Anticancer Res. 2014; 34(10):5351-5 [PubMed] Related Publications
BACKGROUND: Glioblastoma multiforme (GBM) is one of the deadliest cancers characterized by very limited sensitivity to chemo- and/or radiotherapy. The presence of GBM stem-like cells in the tumor might be relevant for GBM treatment resistance.
AIM: To provide a proof-of-concept of the efficacy of photon activation therapy (PAT) using monochromatic synchrotron radiation (SR), in killing GBM stem cells pre-treated with cisplatin.
MATERIALS AND METHODS: Irradiation was performed using a 1-8 Gy dose range and energies just above or below the platinum K-shell edge (78.39 keV) or with a conventional X-ray source. Cells were exposed to drug concentrations allowing 90% cell survival, mimicking the unfavourable tissue distribution generally achieved in GMB patients.
RESULTS: a significant enhancement in cell lethality was observed using SR compared to conventional X-ray irradiation.
CONCLUSION: PAT deserved to be further explored in in vivo models based on GBM stem-like cells.

Related: Cisplatin

Longo L, Slater S
Challenges in providing culturally-competent care to patients with metastatic brain tumours and their families.
Can J Neurosci Nurs. 2014; 36(2):8-14 [PubMed] Related Publications
Being diagnosed with a metastatic brain tumour can be devastating as it is characterized by very low cure rates, as well as significant morbidity and mortality. Given the poor life expectancy and progressive disability that ensues, patients and family members experience much turmoil, which includes losses that bring about changes to family roles, routines and relationships. Crisis and conflict are common during such major disruptions to a family system, as individual members attempt to make sense of the illness experience based on cultural and spiritual beliefs, past experiences and personal philosophies. It is imperative health care providers strive towards increased awareness and knowledge of how culture affects the overall experience of illness and death in order to help create a mutually satisfactory care plan. Providing culturally-competent care entails the use of proper communication skills to facilitate the exploration of patient and family perspectives and allows for mutual decision making. A case study will illustrate the challenges encountered in providing culturally-competent care to a woman with brain cancer and her family. As the patient's health declined, the family entered into a state of crisis where communication between family members and health care professionals was strained; leading to conflict and sub-optimal outcomes. This paper will address the ethical dilemma of providing culturally-competent care when a patient's safety is at risk, and the nursing implications of upholding best practices in the context of differing beliefs and priorities.

Related: Lung Cancer

Mille F, Tamayo-Orrego L, Lévesque M, et al.
The Shh receptor Boc promotes progression of early medulloblastoma to advanced tumors.
Dev Cell. 2014; 31(1):34-47 [PubMed] Related Publications
During cerebellar development, Sonic hedgehog (Shh) signaling drives the proliferation of granule cell precursors (GCPs). Aberrant activation of Shh signaling causes overproliferation of GCPs, leading to medulloblastoma. Although the Shh-binding protein Boc associates with the Shh receptor Ptch1 to mediate Shh signaling, whether Boc plays a role in medulloblastoma is unknown. Here, we show that BOC is upregulated in medulloblastomas and induces GCP proliferation. Conversely, Boc inactivation reduces proliferation and progression of early medulloblastomas to advanced tumors. Mechanistically, we find that Boc, through elevated Shh signaling, promotes high levels of DNA damage, an effect mediated by CyclinD1. High DNA damage in the presence of Boc increases the incidence of Ptch1 loss of heterozygosity, an important event in the progression from early to advanced medulloblastoma. Together, our results indicate that DNA damage promoted by Boc leads to the demise of its own coreceptor, Ptch1, and consequently medulloblastoma progression.

Related: Childhood Medulloblastoma / PNET Signal Transduction

Arslan A, Guney Y, Cihan YB, Cetindag MF
Characteristics of childhood glial tumors, management approaches and life expectancy of the patients.
J BUON. 2014 Jul-Sep; 19(3):724-32 [PubMed] Related Publications
PURPOSE: To evaluate the clinical characteristics, management approaches and life expectancy in pediatric patients with neuroepithelial glial tumors except ependymal tumors.
METHODS: Between January 2003 and August 2008, 48 patients (30 boys, 18 girls; mean age: 10.9 ± 4.6 years) who were diagnosed with neuroepithelial glial tumors except ependymal tumors and underwent curative radiotherapy (RT) for inoperable, postoperative adjuvant or palliative for residual/recurrent disease at Dr. Abdurahman Yurtsalan Ankara Oncology Education and Research Hospital, Radiation Oncology Clinic, were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were evaluated in relation to sex, previous surgical procedure, pathological diagnosis, low/high grade and the histopathological grade of disease.
RESULTS: The mean follow-up was 28.8 ± 4.8 months. The mean and median PFS were 36.2 months and 20 months, respectively, while mean and median OS were 40.3 months and 23 months, respectively. One-year PFS and OS were 65.8% and 71%, respectively, whereas 3-year PFS and OS were 36.3% and 42.3%, respectively. Univariate Cox regression model and Log-Rank test revealed no statistical significance. Prolonged PFS and OS were observed in boys compared to girls, those who underwent total/gross total resection compared to subtotal resection, those with low grade tumors compared to high-grade tumors, and those with histopathological grade I disease compared to grade IV disease (p>0.05). The PFS and OS times were shortened in patients who developed side effects at any time following surgery and RT, compared to those without any side effects (p>0.05).
CONCLUSION: Low-grade disease and total/gross total resection prolong PFS and OS in patients with childhood glial tumors.

Related: Childhood Brain Tumours Childhood Brain Tumors Brain Stem Glioma - Childhood

Peponi E, Tourkantonis I, Tasiou I, et al.
Prognostic factors in glioblastoma patients managed with radiotherapy combined with temozolomide.
J BUON. 2014 Jul-Sep; 19(3):718-23 [PubMed] Related Publications
PURPOSE: No consensus on clinicopathologic prognostic factors that predict the outcome of patients with newly diagnosed glioblastoma multiforme (GBM) managed with resection, postoperative radiotherapy (RT) and adjuvant temozolomide (TMZ) exists today. The purpose of this study was to assess the outcome, compliance and toxicity in GBM patients treated with TMZ at our Center, as well as to evaluate factors with prognostic significance.
METHODS: 91 GBM patients were enrolled in this retrospective study (2004-2012). 3D-conformal RT was given to a median total dose of 60Gy (daily dose 2Gy). Eighty nine (98%) of the patients received concurrent TMZ (75mg/m²) and 74 (81%) received adjuvant TMZ (150-200mg/m² for 5 days every 28 days) up to 12 cycles.
RESULTS: At a mean follow up of 18.6 months, the median overall survival (OS) was 15.1 months. Grade 3/4 haematologic toxicity was observed in 19.8% of the patients while 4 patients (4.4%) experienced grade 3/4 non haematologic toxicity. In univariate analysis, significant correlation was found between OS and no/minor neurologic deficit at diagnosis (p=0.02), acute onset of symptoms (p=0.04) and 6 cycles of adjuvant TMZ (p<0.001). The addition of more than 6 cycles of TMZ did not offer any statistically significant survival benefit. In multivariate analysis, only the absence of major neurologic deficit remained associated with overall survival (p=0.016).
CONCLUSION: 3D conformal RT with TMZ achieved acceptable disease control with satisfactory compliance and toxicity. Intact neurologic function was associated with superior outcome, as a surrogate of low tumor burden, early treatment start and/or indolent tumor biology.

Related: Dacarbazine Temozolomide

Wang X, Zhao HY, Zhang FC, et al.
Dendritic cell-based vaccine for the treatment of malignant glioma: a systematic review.
Cancer Invest. 2014; 32(9):451-7 [PubMed] Related Publications
OBJECTIVE: Glioblastoma multiforme (GBM) has a poor prognosis. The purpose of this systematic review and meta-analysis was to analyze the outcomes of clinical trials which compared immunotherapy with conventional therapy for the treatment of malignant gliomas.
METHODS: PubMed, Cochrane and Google Scholar databases were searched for relevant studies. The 2-year survival rate was used to evaluate effectiveness of immunotherapy.
RESULTS: Of 171 studies identified, six comparative trials were included in the systematic review. Immunotherapy was associated with a significantly longer OS and 2-year survival compared to conventional therapy.
CONCLUSION: Immunotherapy may improve the survival of patients with GBM.

Smith SJ, Rahman CV, Clarke PA, et al.
Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma.
Ann R Coll Surg Engl. 2014; 96(7):495-501 [PubMed] Related Publications
INTRODUCTION: The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.
METHODS: Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.
RESULTS: Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.
CONCLUSIONS: Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.

Qing HS, Shuhui G, Jiagang L
Surgical management of intramedullary cavernous angiomas and analysis pain relief.
Neurol India. 2014 Jul-Aug; 62(4):423-8 [PubMed] Related Publications
OBJECTIVE: The objective of this study was to conduct a retrospective analysis of the clinical characteristics of 20 individuals with intramedullary cavernous angiomas (ICA) presented with serious pain complaints. This study was to investigate the efficacy of short- and long-term pain relief following surgical resection.
MATERIALS AND METHODS: Between 2006 and 2012, 55 patients with ICA were surgically managed in our institution. Of these 20 (36.4%) patients presented with serious pain as a unique clinical feature. Numerical pain scores (NPS: 0-10) were used to assess the patients' pain levels preoperatively, as well as at 1 month and 1 year postoperatively. All the patients had magnetic resonance imaging (MRI) preoperatively and during follow-up. IBM SPSS Statistics 19.0 was used to analysis the outcomes.
RESULTS: Of the 20 patients with ICA, 9 (45%) required cervical and 11 (55%) thoracic surgery. Seven (35%) patients presented with radicular pain and 13 (65%) presented with central pain. Pain improved from a total mean preoperative score of 8.60 to total mean score of 2.95 (P < 0.01) at one month and 3.35 (P < 0.01) at one year post-surgery. However, the pain symptoms completely disappeared in the long-term follow-up only in three (15%) patients. Five (25%) patients reported new pain symptoms with no lesion reoccurrence postoperatively.
CONCLUSION: Pain is the common complaint in patients with ICA. Surgery is effective in providing short- and long-term pain relief. However, long-term follow-up measures on postoperative pain levels show that the pain does recur in the months following surgery.

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