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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).

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.

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

Both S, Shen J, Kirk M, et al.
Development and clinical implementation of a universal bolus to maintain spot size during delivery of base of skull pencil beam scanning proton therapy.
Int J Radiat Oncol Biol Phys. 2014; 90(1):79-84 [PubMed] Related Publications
PURPOSE: To report on a universal bolus (UB) designed to replace the range shifter (RS); the UB allows the treatment of shallow tumors while keeping the pencil beam scanning (PBS) spot size small.
METHODS AND MATERIALS: Ten patients with brain cancers treated from 2010 to 2011 were planned using the PBS technique with bolus and the RS. In-air spot sizes of the pencil beam were measured and compared for 4 conditions (open field, with RS, and with UB at 2- and 8-cm air gap) in isocentric geometry. The UB was applied in our clinic to treat brain tumors, and the plans with UB were compared with the plans with RS.
RESULTS: A UB of 5.5 cm water equivalent thickness was found to meet the needs of the majority of patients. By using the UB, the PBS spot sizes are similar with the open beam (P>.1). The heterogeneity index was found to be approximately 10% lower for the UB plans than for the RS plans. The coverage for plans with UB is more conformal than for plans with RS; the largest increase in sparing is usually for peripheral organs at risk.
CONCLUSIONS: The integrity of the physical properties of the PBS beam can be maintained using a UB that allows for highly conformal PBS treatment design, even in a simple geometry of the fixed beam line when noncoplanar beams are used.

Related: Head and Neck Cancers Head and Neck Cancers - Molecular Biology

Wolfson J, Sun CL, Kang T, et al.
Impact of treatment site in adolescents and young adults with central nervous system tumors.
J Natl Cancer Inst. 2014; 106(8):dju166 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
BACKGROUND: Adolescents and young adults (AYAs; aged 15-39 years) have inferior survival in comparison with younger (aged 0-14 years) cancer patients. Impact of care at specialized centers such as National Cancer Institute-designated Comprehensive Cancer Centers (NCICCC) for AYAs of all ages or the Children's Oncology Group (COG) for AYAs aged 15 to 21 years with central nervous system (CNS) tumors remains unstudied.
METHODS: We constructed a cohort of 560 children and 784 AYAs with CNS tumors reported to the Los Angeles cancer registry from 1998 to 2008. Cox and logistic regression models were used, with two-sided P values from Wald χ(2) tests.
RESULTS: In Cox regression analysis restricted to World Health Organization (WHO) grade II tumors, patients of all ages saw worse outcome if not treated at NCICCC/COG sites (non-NCICCC/COG vs NCICCC/COG: hazard ratio [HR] =1.73; 95% confidence interval [CI] = 1.09 to 2.72). Furthermore, the worse outcome for AYAs compared with children (HR = 1.90; 95% CI = 1.21 to 2.98; P = .005) was abrogated (HR = 1.35; 95% CI = 0.79 to 2.29; P = .27) by care at NCICCC/COGs. Those less likely to receive care at NCICCC/COG sites included young AYAs (aged 15-21 years vs children: odds ratio [OR] = 0.23; 95% CI = 0.11 to 0.48; P < .001) and older AYAs (aged 22-39 years) with low socioeconomic status (OR = 0.39; 95% CI = 0.17 to 0.89; P = .02), public/no insurance (OR = 0.30; 95% CI = 0.12 to 0.71; P < .01), and distance to care greater than 5 miles (OR = 0.29; 95% CI = 0.15 to 0.57; P < .001).
CONCLUSIONS: Population-based data reveal that care at NCICCC/COG sites mitigates inferior outcome in AYAs with WHO grade II CNS tumors compared with children. Compared with children, AYAs are less likely to receive care at NCICCC/COGs. Insurance, socioeconomic status, and distance serve as barriers to care at NCICCCs for older AYAs.

Xiao A, Li Z, He X, You C
A rare tentorial mesenchymal chondrosarcoma in posterior cranial fossa: case report.
Neurol Neurochir Pol. 2014; 48(4):287-91 [PubMed] Related Publications
Intracranial extraskeletal mesenchymal chondrosarcoma is a very rare malignant tumor with predilection site of frontoparietal falx cerebri. Only few cases of mesenchymal chondrosarcoma in posterior cranial fossa are reported. Here, we report a 23-year-old young man with a dura-attached mass in left posterior cranial fossa misdiagnosed as a tentorial meningioma preoperatively. According to the following operation, the lesion was confirmed as mesenchymal chondrosarcoma surgically and pathologically. On MRI, the tumor was characterized by lobulated soft-tissue mass with dura-attached base, patchy calcifications and heterogeneous signal intensities. On contrast-enhanced MRI, it was well-defined, with marked enhancement. We consider that these imaging features above might remind us to consider the diagnosis of mesenchymal chondrosarcoma in posterior cranial fossa. The postoperative treatment of radiotherapy is still controversial. As for our case, according to the 24 months follow-up after postoperative γ-knife, our patient shows an optimistic prognosis so far.

Related: Mesenchymal Chondrosarcoma

He X, Zhang L, Chen Y, et al.
The G protein α subunit Gαs is a tumor suppressor in Sonic hedgehog-driven medulloblastoma.
Nat Med. 2014; 20(9):1035-42 [PubMed] Related Publications
Medulloblastoma, the most common malignant childhood brain tumor, exhibits distinct molecular subtypes and cellular origins. Genetic alterations driving medulloblastoma initiation and progression remain poorly understood. Herein, we identify GNAS, encoding the G protein Gαs, as a potent tumor suppressor gene that, when expressed at low levels, defines a subset of aggressive Sonic hedgehog (SHH)-driven human medulloblastomas. Ablation of the single Gnas gene in anatomically distinct progenitors in mice is sufficient to induce Shh-associated medulloblastomas, which recapitulate their human counterparts. Gαs is highly enriched at the primary cilium of granule neuron precursors and suppresses Shh signaling by regulating both the cAMP-dependent pathway and ciliary trafficking of Hedgehog pathway components. Elevation in levels of a Gαs effector, cAMP, effectively inhibits tumor cell proliferation and progression in Gnas-ablated mice. Thus, our gain- and loss-of-function studies identify a previously unrecognized tumor suppressor function for Gαs that can be found consistently across Shh-group medulloblastomas of disparate cellular and anatomical origins, highlighting G protein modulation as a potential therapeutic avenue.

Related: Childhood Medulloblastoma / PNET Signal Transduction

Gnjidić Z, Kudelić N, Sajko T, et al.
Surgical treatment of prolactinomas--our experience.
Coll Antropol. 2014; 38(2):571-6 [PubMed] Related Publications
The dilemma of whether to apply surgical or drug treatment to prolactinomas has been ongoing for the past 30 years. The aim of this study is to compare the early postoperative values of prolactin (PRL) in two groups of patients with prolactinomas: those who underwent primary surgical-treatment, and those who underwent surgery after a dopamine agonist (DA) therapy. We present the results of surgical treatment on a series of 161 patients with prolactinomas. Surgery was the primary treatment in 65 patients, while 96 patients had surgery following a long-term treatment with a DA. All surgically treated prolactinomas were operated in the standard transsphenoidal, microsurgical approach. The criteria for hyperprolactinemia remission was a PRL level under 25 ng/ml. Early normalization of PRL was achieved in 92% of those patients who underwent primary surgical-treatment, yet it was achieved in only 42% of patients who were operated on after receiving a long-term drug treatment with a DA. The highest prevalence of postoperative normalization of PRL was achieved in a group of patients with microadenomas who were primarily operated on (98%). The worst results in postoperative normalization of PRL were found in the group of patients with macroadenomas who received a long-term drug treatment with a DA first. These results show our surgical experience in treating prolactinomas. Using surgical treatment, the best clinical outcome was achieved with microprolactinomas and intrasellar, well-confined macroprolactinomas. Nevertheless, we stress the need of an individualized approach and recommend treatment in multidisciplinary centres for pituitary diseases.

Related: Pituitary Tumors

Bierman PJ
Surgery for primary central nervous system lymphoma: is it time for reevaluation?
Oncology (Williston Park). 2014; 28(7):632-7 [PubMed] Related Publications
The overall survival rate for primary central nervous system lymphoma (PCNSL) has improved significantly. This prolongation in survival is related mainly to advances in chemotherapy regimens and radiotherapy. In contrast, the role of surgery in PCNSL has been limited because tumors are frequently not amenable to resection and because most studies have failed to show that resection is beneficial. A recent analysis of the German Primary CNS Lymphoma Study Group 1 (G-PCNSL-SG-1) trial has challenged this convention by showing that the survival of patients with PCNSL may actually be prolonged if tumors are resected. While there are a number of weaknesses in the analysis, many authorities now feel that an attempt at gross total resection is reasonable for patients with solitary lesions that can be removed without morbidity. However, even if resection does benefit some patients, the diagnosis of lymphoma is almost always made in retrospect, and there are few occasions when a neurosurgeon will actually need to make a decision whether or not to resect a known PCNSL.

Lim E, Lin NU
Updates on the management of breast cancer brain metastases.
Oncology (Williston Park). 2014; 28(7):572-8 [PubMed] Related Publications
Breast cancer brain metastases (BCBMs) are common in patients with advanced disease. Breast cancer subtype and performance status are the major determinants of the course of the disease and survival time following a diagnosis of brain metastasis. Unique challenges specific to the management of BCBMs include overcoming the blood-brain barrier and resistance to conventional systemic therapies, as BCBMs typically occur in the pretreated patient population. The development of new systemic therapies for breast cancer, coupled with improvements in trial design, imaging modalities, and methods of defining and measuring clinical endpoints, has led to a renewed interest in developing novel therapeutic approaches for BCBMs. In this overview, we will review recent developments in the management of BCBMs and current prospective trials of systemic therapies specifically for patients with BCBMs, with a focus on novel pathway-specific therapies.

Related: Breast Cancer Signal Transduction

Kobayashi K, Imagama S, Ito Z, et al.
Recurrence of solitary fibrous tumor of the cervical spinal cord.
Nagoya J Med Sci. 2014; 76(1-2):217-23 [PubMed] Related Publications
Solitary fibrous tumor (SFT) mostly originates from the pleura because of proliferation of fibroblast cells. It is extremely rare for the tumor to originate from the spinal cord. Here, we report a rare case of SFT in the spinal cord that recurred repeatedly and progressed from intramedullary to extramedullary. A 40-year-old man underwent C4-5 intramedullary and extramedullary tumor resection in another hospital. Eighteen years later, he experienced symptoms of myelopathy because of tumor recurrence; therefore, he consulted with our hospital and underwent tumor resection again. During surgery, we found that the tumor had an intramedullary and extramedullary location. Only partial resection was possible because of intraoperative deterioration in the compound motor action potential (CMAP). After resection, the pathological diagnosis was SFT. The postoperative course was good. However, two years later, a third tumor resection was required because of dysuria and tumor growth. In this surgery, total resection of the tumor was possible without intraoperative deterioration of the CMAP. The tumor has not subsequently recurred. However, SFT recurrence is relatively common and careful follow-up is required for early detection of recurrence, even after successful removal of the tumor.

Kobayashi T, Tsugawa T, Hashizume C, et al.
Gamma knife radiosurgery of brain metastasis from malignant pleural mesothelioma--report of three cases with autopsy study in a case.
Nagoya J Med Sci. 2014; 76(1-2):187-93 [PubMed] Related Publications
The median survival time of malignant pleural mesothelioma (MPM) has been 9 months. Given the short survival, there have been only few cases in which brain metastases have been diagnosed and treated before death. Three cases of brain metastases treated by gamma knife radiosurgery (GKR) are reported. Case I showed a metastatic lesion in the right frontal lobe which was treated by GKR two years after diagnosis of MPM. The lesion markedly reduced and the symptoms were improved, But the patient died of progression of pleural tumor four months after GKR. A year and three months after the diagnosis, asymptomatic bifrontal lesions were treated with GKR. However, Case 2 died of abdominal mass a month after. Case 3 showed headache one and half year after the diagnosis. Three brain lesions were treated by GKR, which disappeared in 4 months. The patient died of new multiple brain metastases and periventricular dissemination seven months after. The autopsy revealed a MPM occupying the left pleural cavity. No neoplastic lesion was found in gamma knife-treated sites. The cause of death was the mass effect by new metastatic lesions. GKR was found effective also for the treatment of brain metastasis of MPM.

Takeuchi K, Nagatani T, Okumura E, Wakabayashi T
A novel method for managing water and electrolyte balance after transsphenoidal surgery: preliminary study of moderate water intake restriction.
Nagoya J Med Sci. 2014; 76(1-2):73-82 [PubMed] Related Publications
Hyponatremia is a common and potentially serious complication of transsphenoidal surgery (TSS). Since September 2009, we have implemented moderate water intake restriction (< 2500 mL/day) after TSS in an attempt to prevent this complication. The aim of this study was to investigate the efficacy of a combination of moderate restriction of water intake plus antidiuretic hormone (arginine vasopressin [AVP]) replacement therapy in patients with diabetes insipidus (DI) for reducing the incidence of delayed hyponatremia after TSS. Patients treated from September 2005 to August 2009 were allowed to drink water freely after surgery (the control group), while patients treated from September 2009 to June 2012 were restricted to less than 2500 mL water per day (the water restriction group). To reduce the occurrence of hypernatremia, AVP replacement therapy was provided immediately after the development of DI. We retrospectively analyzed the incidence of hyponatremia, DI, and hypernatremia in patients following TSS. Hyponatremia incidence was significantly lower in the water restriction group (P = 0.017); however, there were no significant differences in DI incidence and hypernatremia incidence between the 2 groups. Under DI control with AVP replacement therapy, the water restriction group showed no significant difference in the daily self-rated thirst level for the patients with and without DI. Moderate water intake restriction in addition to AVP replacement therapy significantly decreases the incidence of hyponatremia without patient discomfort (extreme thirst) and other complications. However, further studies are required to determine the most effective amount of water and the optimal duration of postoperative water restriction.

Related: Pituitary Tumors

Qiu XX, Chen L, Wang CH, et al.
High delta-like ligand 4 (DLL4) is correlated with peritumoral brain edema and predicts poor prognosis in primary glioblastoma.
Medicine (Baltimore). 2014; 93(8):e57 [PubMed] Related Publications
Delta-like ligand 4 (DLL4), 1 of the 5 known Notch ligands, is involved in a variety of tumor initiation and progression, particularly in the process of tumor angiogenesis. However, the clinical and prognostic significance of DLL4 in glioblastoma have not been fully elucidated.Tumor tissues from 69 glioblastoma patients were analyzed using immunohistochemistry for DLL4 expression. Peritumoral brain edema (PTBE) on preoperative magnetic resonance imaging of these patients and the relationship with DLL4 expression were evaluated. The effect on prognosis was assessed by using the Kaplan-Meier survival and the Cox proportional hazard model.The results showed that elevated DLL4 expression was primarily distributed in the cytoplasm of tumor vascular endothelial cells and rarely detected in tumor cells. Univariate analysis indicated significant correlation of high DLL4 expression with shorter time to progression (TTP) (P < 0.001) and overall survival (OS) (P < 0.001) in glioblastoma. Multivariate analysis confirmed high DLL4 expression as an unfavorable prognostic indicator for TTP (P < 0.001) and OS (P < 0.001), independent of age, gender, symptom duration, resection degree, and PTBE. Importantly, the study also found that DLL4 expression was positively related with PTBE (Spearman's test: r = 0.845, P < 0.001). A multiple linear regression model was constructed to confirm that the positive index of DLL4 was associated with an increase in maximum extent of PTBE (P < 0.001).It is thus concluded that DLL4 is correlated with PTBE and may be useful for predicting prognosis in glioblastoma.

Piura E, Piura B
Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature.
Eur J Gynaecol Oncol. 2014; 35(4):359-67 [PubMed] Related Publications
Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months.

Ozawa T, Riester M, Cheng YK, et al.
Most human non-GCIMP glioblastoma subtypes evolve from a common proneural-like precursor glioma.
Cancer Cell. 2014; 26(2):288-300 [PubMed] Article available free on PMC after 11/08/2015 Related Publications
To understand the relationships between the non-GCIMP glioblastoma (GBM) subgroups, we performed mathematical modeling to predict the temporal sequence of driver events during tumorigenesis. The most common order of evolutionary events is 1) chromosome (chr) 7 gain and chr10 loss, followed by 2) CDKN2A loss and/or TP53 mutation, and 3) alterations canonical for specific subtypes. We then developed a computational methodology to identify drivers of broad copy number changes, identifying PDGFA (chr7) and PTEN (chr10) as driving initial nondisjunction events. These predictions were validated using mouse modeling, showing that PDGFA is sufficient to induce proneural-like gliomas and that additional NF1 loss converts proneural to the mesenchymal subtype. Our findings suggest that most non-GCIMP mesenchymal GBMs arise as, and evolve from, a proneural-like precursor.

Related: Chromosome 10 Chromosome 7 PTEN PDGFB gene PDGFRA gene EGFR

Zadeh G, Aldape K
RESICstance is futile-but not in glioblastoma.
Cancer Cell. 2014; 26(2):156-7 [PubMed] Related Publications
Genomic alterations that occur early in tumorigenesis represent fundamental diver lesions and are perhaps of highest priority as a means to intervene therapeutically. In this issue of Cancer Cell, Ozawa and colleagues apply an algorithm to identify early events in glioblastoma and validate their findings in a rigorous manner.

Bernstein M
Neuro-oncology: Under-recognized mental incapacity in brain tumour patients.
Nat Rev Neurol. 2014; 10(9):487-8 [PubMed] Related Publications
Many patients with brain tumours possess inadequate mental capacity to provide informed consent, but this situation often goes undetected because clinicians do not routinely conduct formal cognitive assessments. This oversight should be recognized and rectified to enable optimum ethical and medical care of these vulnerable individuals.

Peretz B, Sarnat H, Kharouba J
Chemotherapy induced dental changes in a child with medulloblastoma: a case report.
J Clin Pediatr Dent. 2014; 38(3):251-4 [PubMed] Related Publications
We describe the dental findings and therapeutic management of a child aged three years and eight months with medulloblastoma treated by surgical resection at age eight months followed by 20 months of chemotherapy. Thin and short roots of the primary molars were observed, as were microdontia and anodontia of the premolars. The boy suffered from severe early childhood caries (ECC). Dental treatment was carried out under general anesthesia. Follow-up examinations at three, six and twelve months after the initial dental treatment revealed healthy gingival tissue and no new caries. The boy passed away before the next scheduled follow-up dental examination.

Related: Childhood Medulloblastoma / PNET

Bast F, Schrom T
Neurological symptoms of leptomeningeal carcinomatosis as the primary manifestation of an adenocarcinoma of the nasal cavity and sinus: a case report and literature review.
B-ENT. 2014; 10(2):157-60 [PubMed] Related Publications
Carcinomas of the nose and paranasal sinuses are rare solid head and neck tumours. With an incidence of 1-1.5/100,000 per year, they account for only 3% of all malignancies in the head and neck region. Sinonasal carcinomas are often adenocarcinomas. Hardwood dust is one possible triggering agent, although the latency period may extend to decades. Central nervous system complications arising from solid tumours of the head can be explained in terms of the close anatomical relationship between the two areas. However, leptomeningeal spread is rare. To our knowledge, this is the first report demonstrating cranial nerve deficits due to a leptomeningeal carcinomatosis as the primary manifestation of an adenocarcinoma of the paranasal sinus and the nasal cavity.

Sevenich L, Bowman RL, Mason SD, et al.
Analysis of tumour- and stroma-supplied proteolytic networks reveals a brain-metastasis-promoting role for cathepsin S.
Nat Cell Biol. 2014; 16(9):876-88 [PubMed] Related Publications
Metastasis remains the most common cause of death in most cancers, with limited therapies for combating disseminated disease. While the primary tumour microenvironment is an important regulator of cancer progression, it is less well understood how different tissue environments influence metastasis. We analysed tumour-stroma interactions that modulate organ tropism of brain, bone and lung metastasis in xenograft models. We identified a number of potential modulators of site-specific metastasis, including cathepsin S as a regulator of breast-to-brain metastasis. High cathepsin S expression at the primary site correlated with decreased brain metastasis-free survival in breast cancer patients. Both macrophages and tumour cells produce cathepsin S, and only the combined depletion significantly reduced brain metastasis in vivo. Cathepsin S specifically mediates blood-brain barrier transmigration through proteolytic processing of the junctional adhesion molecule, JAM-B. Pharmacological inhibition of cathepsin S significantly reduced experimental brain metastasis, supporting its consideration as a therapeutic target for this disease.

Related: Breast Cancer

Tjörnstrand A, Gunnarsson K, Evert M, et al.
The incidence rate of pituitary adenomas in western Sweden for the period 2001-2011.
Eur J Endocrinol. 2014; 171(4):519-26 [PubMed] Related Publications
OBJECTIVE: The number of studies on the incidence of pituitary adenomas (PAs) is limited. The aim of this study was to evaluate the standardised incidence rate (SIR) of PAs in western Sweden.
DESIGN, SUBJECTS AND METHODS: Data from adult patients diagnosed with PAs in 2001-2011, living in the Västra Götaland County, were collected from the Swedish Pituitary Registry (SPR). In addition, medical records on all patients diagnosed with PAs at the six hospitals in the region were reviewed. In total, 592 patients were included in the study.Age-SIR, given as rate/100 000 inhabitants (95% CI), was calculated using the WHO 2000 standard population as a reference.
RESULTS: The total SIR for PAs was 3.9/100 000 (3.6-4.3); 3.3/100 000 (2.9-3.7) for men and 4.7/100 000 (4.1-5.3) for women. In men, SIR increased with age, while in women SIR peaked at 25-34 years, mainly due to prolactinomas. Non-functioning PA (NFPA) was the most common PA (54%, 1.8/100 000 (1.6-2.0)) followed by prolactinomas (32%, 1.6/100 000 (1.3-1.9)), acromegaly (9%, 0.35/100 000 (0.25-0.45)), Cushing's disease (4%, 0.18/100 000 (0.11-0.25)) and TSH-producing PA (0.7%, 0.03/100 000 (0.00-0.05)). The proportion of macroadenomas for NFPA was 82%, prolactinomas 37%, GH-producing PA 77%, ACTH-producing PA 28% and TSH-producing PA 100%. The lifetime risk for PAs was 0.27% (0.24-0.31) in men and 0.29% (0.26-0.33) in women.
CONCLUSION: This study provides a reliable estimate on the overall incidence of PAs and confirms an increased incidence of PAs compared with studies conducted in the pre-magnetic resonance imaging era. The lower proportion of prolactinomas compared with previous studies is probably explained by the different criteria used.

Related: Pituitary Tumors

Shamisa A, Bance M, Nag S, et al.
Glioblastoma multiforme occurring in a patient treated with gamma knife surgery: case report and review of the literature.
J Neurosurg. 2013; 119 Suppl:816-21 [PubMed] Related Publications
Stereotactic radiosurgery is being increasingly advocated as the primary modality for treatment of vestibular schwannomas (VS). This modality has been shown to arrest tumor growth, with few associated short-term morbidities, and with possibly better hearing and facial nerve preservation rates than microsurgery. Radiation-induced oncogenesis has long been recognized, although stereotactic radiosurgery de novo induction of a secondary tumor has never been clearly described. The authors report on a patient with a VS who did not have neurofibromatosis Type 2 and who underwent gamma knife surgery (GKS). This patient required microsurgical removal of the VS within 8 months because of development of a tumor cyst with associated brainstem compression and progressive hydrocephalus. The operation resulted in clinical stabilization and freedom from tumor recurrence. Seven and a half years after undergoing GKS, the patient presented with symptoms of raised intracranial pressure. Magnetic resonance imaging demonstrated a new ring-enhancing lesion in the inferior temporal lobe adjacent to the area of radiosurgery, which on craniotomy was confirmed to be a glioblastoma multiforme (GBM). Despite additional conventional external-beam radiation to the temporal lobe, the GBM has progressed. Whereas this first reported case of a GBM within the scatter field of GKS does not conclusively prove a direct causal link, it does fulfill all of Cahan's criteria for radiation-induced neoplasia, and demands increased vigilance for the potential long-term complications of stereotactic radiosurgery, and reporting of any similar cases.

Related: Acoustic Neuroma

Iordache A, Cosman M, Dumitrescu GF, Poeată I
Singular case of third ventricle metastasis of colorectal carcinoma--case report.
Rev Med Chir Soc Med Nat Iasi. 2014 Apr-Jun; 118(2):427-31 [PubMed] Related Publications
Third ventricle tumors are uncommon central nervous system lesions and unusual locations for metastatic colorectal cancer. We present a case of a 68 year old woman with a solitary 3rd ventricle lesion found on a computed tomography scan of the brain and the synchronous mass of the right colon. The aim in this case was local control of cerebral lesion with pathological diagnosis. Surgery was followed by a short-term good evolution but with sudden death.

Related: Colorectal (Bowel) Cancer

Cheah CY, Herbert KE, O'Rourke K, et al.
A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma.
Br J Cancer. 2014; 111(6):1072-9 [PubMed] Related Publications
BACKGROUND: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear.
METHODS: We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX 'group 3'.
RESULTS: Overall, 217 patients were identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of 3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5-33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively (P=0.009).
CONCLUSIONS: The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.

Related: Cyclophosphamide Cytarabine Doxorubicin Etoposide Ifosfamide Methotrexate Vincristine Rituximab (Mabthera)

Zukotynski K, Fahey F, Kocak M, et al.
18F-FDG PET and MR imaging associations across a spectrum of pediatric brain tumors: a report from the pediatric brain tumor consortium.
J Nucl Med. 2014; 55(9):1473-80 [PubMed] Related Publications
UNLABELLED: The purpose of this study was to describe (18)F-FDG uptake across a spectrum of pediatric brain tumors and correlate (18)F-FDG PET with MR imaging variables, progression-free survival (PFS), and overall survival (OS).
METHODS: A retrospective analysis was conducted of children enrolled in phase I/II clinical trials through the Pediatric Brain Tumor Consortium from August 2000 to June 2010. PET variables were summarized within diagnostic categories using descriptive statistics. Associations of PET with MR imaging variables and PFS and OS by tumor types were evaluated.
RESULTS: Baseline (18)F-FDG PET was available in 203 children; 66 had newly diagnosed brain tumors, and 137 had recurrent/refractory brain tumors before enrolling in a Pediatric Brain Tumor Consortium trial. MR imaging was performed within 2 wk of PET and before therapy in all cases. The (18)F-FDG uptake pattern and MR imaging contrast enhancement (CE) varied by tumor type. On average, glioblastoma multiforme and medulloblastoma had uniform, intense uptake throughout the tumor, whereas brain stem gliomas (BSGs) had low uptake in less than 50% of the tumor and ependymoma had low uptake throughout the tumor. For newly diagnosed BSG, correlation of (18)F-FDG uptake with CE portended reduced OS (P = 0.032); in refractory/recurrent BSG, lack of correlation between (18)F-FDG uptake and CE suggested decreased PFS (P = 0.023). In newly diagnosed BSG for which more than 50% of the tumor had (18)F-FDG uptake, there was a suggestion of lower apparent diffusion coefficient (P = 0.061) and decreased PFS (P = 0.065).
CONCLUSION: (18)F-FDG PET and MR imaging showed a spectrum of patterns depending on tumor type. In newly diagnosed BSG, the correlation of (18)F-FDG uptake and CE suggested decreased OS, likely related to more aggressive disease. When more than 50% of the tumor had (18)F-FDG uptake, the apparent diffusion coefficient was lower, consistent with increased cellularity. In refractory/recurrent BSG, poor correlation between (18)F-FDG uptake and CE was associated with decreased PFS, which may reflect concurrent tissue breakdown at sites of treated disease and development of new sites of (18)F-FDG-avid malignancy.

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

Khan UA, Shanholtz CB, McCurdy MT
Oncologic mechanical emergencies.
Emerg Med Clin North Am. 2014; 32(3):495-508 [PubMed] Related Publications
Prevalence of cancer and its various related complications continues to rise. Increasingly these life-threatening complications are initially managed in the emergency department, making a prompt and accurate diagnosis crucial to effectively institute the proper treatment and establish goals of care. The following oncologic emergencies are reviewed in this article: pericardial tamponade, superior vena cava syndrome, brain metastasis, malignant spinal cord compression, and hyperviscosity syndrome.

Related: Cancer Prevention and Risk Reduction

Oddone E, Scaburri A, Bai E, et al.
Occupational brain cancer risks in Umbria (Italy), with a particular focus on steel foundry workers.
G Ital Med Lav Ergon. 2014 Apr-Jun; 36(2):111-7 [PubMed] Related Publications
OBJECTIVES: As a part of the Occupational Cancer Monitoring (OCCAM) project, a routine analysis based on Umbria region cancer registry (RTUP) database in 2002-2008 was performed. Among other results, the incidental finding of brain cancer increased risk in steel foundry workers in Terni province (Italy), lead us to deepen the analysis, focusing on this specific industrial sector.
METHODS: A monitoring study, based on Umbria Regional Cancer Registry data, was recently carried out. Brain cancer cases and controls identified within this preliminary study were selected. Therefore, we considered all incident cases (in Umbria region 2002-2008) of brain cancer occurred among workers occupied for at least one year in private companies since 1974 and controls randomly sampled from the same population. Afterwards, taking in to account results from steel foundry in Terni province, we further deepened our analysis, focusing on this productive sector. Odds ratios (ORs) and corresponding 90% confidence intervals (CIs) were calculated using multiple logistic regression models, adjusted by age at diagnosis or sampling, sex and province of residence, when appropriate.
RESULTS: Statistical analyses were carried out on 14913 subjects, 56 cases and 14857 controls. Significantly increased ORs were observed for garment, mechanical manufacturing and chemical industries. Moreover, the risk estimates were strongly correlated with exposures in iron and steel foundries and a cluster of 14 cases in the same foundry in Terni was observed (OR 9.59, 90% CI 2.76-33.34).
CONCLUSIONS: Results of this explorative study showed increased ORs of brain cancer in some productive branches, involving possible exposures to chemical compounds and/or solvents. Moreover, our results pointed out a significantly increased risk in Terni foundry workers, determining an interesting brain cancer cluster (14 cases). Further studies on this industrial sector are needed with improved definitions of tasks and exposures.

Shim H, Wei L, Holder CA, et al.
Use of high-resolution volumetric MR spectroscopic imaging in assessing treatment response of glioblastoma to an HDAC inhibitor.
AJR Am J Roentgenol. 2014; 203(2):W158-65 [PubMed] Related Publications
OBJECTIVE: Improved predictive imaging would enable personalization and adjustment of treatment, which are critical for patients with glioblastomain whom therapy is likely to fail. This article describes the use of MR spectroscopic imaging (MRSI) to predict early clinical and behavioral response to a therapy and an effort to develop high-resolution, volumetric MRSI to improve its clinical application.
CONCLUSION: MRSI may enable quantitative analysis of brain tumor response, offering a precise tool for monitoring of patients in clinical trials.

Gong A, Ge N, Yao W, et al.
Aplysin enhances temozolomide sensitivity in glioma cells by increasing miR-181 level.
Cancer Chemother Pharmacol. 2014; 74(3):531-8 [PubMed] Related Publications
PURPOSE: Aplysin, a natural brominate compound from marine organisms, has been demonstrated to exhibit anti-tumor activity, mainly by inducing apoptosis and cell cycle arrest. However, its effect on glioma is still unknown. In this study, we evaluated the effects of aplysin on the malignant properties of glioma cells and its enhancing effect on temozolomide (TMZ) action against drug-resistant glioma cell lines.
METHODS: We employed several human glioma cell lines and primary glioma cells to address this issue with multidisciplinary approaches.
RESULTS: The combined application of aplysin and TMZ significantly sensitizes glioma cells to TMZ action, compared with TMZ alone. miRNA profile analysis revealed that the abundance of miR-181, an important glioma tumor suppressors believed to enhance TMZ effect, was greatly elevated in aplysin-treated glioma cell lines. The aplysin-induced TMZ sensitivity is dependent on MEK1 in glioma cells. Overexpression of MEK1 was able to abolish the effect of aplysin on glioma cells.
CONCLUSIONS: We found that aplysin can enhance the effect of TMZ on glioma cells by increasing miR-181 expression.

Related: Apoptosis Dacarbazine Temozolomide

Gao X, Jin W
The emerging role of tumor-suppressive microRNA-218 in targeting glioblastoma stemness.
Cancer Lett. 2014; 353(1):25-31 [PubMed] Related Publications
Glioblastoma multiforme (GBM) is by far the most common and most aggressive malignant primary tumor in humans and has poor outcomes despite many advances in treatment using combinations of surgery, radiotherapy and chemotherapy. Recent studies demonstrate that GBM contains a subpopulation of cancer cells with stem cell characteristics, including self-renewal and multipotentiality, and that these cancer stem cells contribute to disease progression. MicroRNAs (miRNAs) are small non-coding regulatory RNA molecules that regulate a variety of cellular processes, including stem cell maintenance. An accumulating body of evidence shows that miR-218 may act as a tumor suppressor by inhibiting glioblastoma invasion, migration, proliferation and stemness through its different targets, indicating the great potential and relevance of miR-218 as a novel class of therapeutic target in glioblastoma.

Related: Apoptosis

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