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Childhood Brain Tumours
Pituitary Tumours
Primary CNS Lymphoma
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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).

Zhang L, Zhao D
Applications of nanoparticles for brain cancer imaging and therapy.
J Biomed Nanotechnol. 2014; 10(9):1713-31 [PubMed] Related Publications
The most common types of malignant brain tumors in adults are brain metastasis and primary glioblastoma multiforme (GBM), both of which are highly lethal, with a median survival of less than a year. A critical challenge in treating brain tumors is the delivery of drugs to the central nervous system (CNS). The blood brain barrier (BBB), which has been shown to be partially disruptive even in the late stage of these brain tumors, prevents the access of therapeutic concentrations of systemic drugs to the tumor in brain parenchyma. Nanoparticle systems can represent optimal carriers for delivery of therapeutic agents. We will summarize various strategies used to improve nano-delivery of imaging contrast or therapeutic agents across BBB to brain tumors. Recent advances in molecular and cellular identifications of neurooncological biomarkers promise the advent of nanotechnology-based brain tumor-targeted detection and therapy. In this review, we will further discuss the current understanding of brain tumor biology and tumor type-specific genetic and epigenetic alterations, and advances in development of the novel nanoparticles for brain tumor imaging and therapy.

Ba JL, Jandial R, Nesbit A, et al.
Current and emerging treatments for brain metastases.
Oncology (Williston Park). 2015; 29(4):250-7 [PubMed] Related Publications
Brain metastasis in patients with cancer can be indicative of multisystem spread or lead to neurological demise if not locally controlled, and is associated with poor survival and high morbidity. Compared with metastasis to other areas of the body, brain metastasis possesses a unique biology that confers high resistance to systemic therapies. This phenomenon has been historically attributed to the inability of chemotherapeutic agents to pass through the blood-brain barrier. Recent studies challenge this premise, revealing other potentially targetable mechanism(s). Therapies that exploit recent advances in the understanding of brain metastasis are still in early stages of development. Encouragingly, and discovered by happenstance, some molecularly targeted drugs already appear to have efficacy against certain tumors and accompanying cerebral edema. In the meantime, conventional treatment modalities such as surgery and radiation have iteratively reached new levels of refinement. However, these achievements are somewhat muted by the emergence of magnetic resonance (MR)-guided laser interstitial thermal therapy, a minimally invasive neuroablative technique. On the horizon, MR-guided focused ultrasound surgery is similarly intriguing. Even in the absence of further advances, local control is frequently achieved with state-of-the-art therapies. Dramatic improvements will likely require sophisticated approaches that account for the particular effects of the microenvironment of the central nervous system on metastasis.

Related: Breast Cancer Colorectal (Bowel) Cancer Kidney Cancer Lung Cancer Skin Cancer

Doron O, Carmon E
An incidental suprasellar mass in a military flying cadet: implications for aircrew.
Aerosp Med Hum Perform. 2015; 86(5):477-80 [PubMed] Related Publications
BACKGROUND: Incidental findings pose a dilemma in aviation medicine, where every finding must be carefully considered in order to ensure the well-being of the aircrew for flight and mission safety. Since suprasellar masses are not uncommon, their possible effects should be addressed.
CASE REPORT: We present an incidental finding of 11.5 mm × 14.4 mm, hyper-intense on T2 and iso-intense on T1-weighted images, of a suprasellar mass in a 19-yr-old man. This finding led to the re-evaluation of his position as a military flight cadet, followed by his later disqualification.
DISCUSSION: No medical waiver regarding asymptomatic suprasellar mass exists. We have carefully examined the differential diagnosis and generated a profile for each possible diagnosis consisting of risks for sudden incapacitation, progression likelihood, and the effect of an aerial environment on a brain lesion. We were able to draw up a medical waiver for some of the possible diagnoses (namely, Rathke's cyst or craniopharyngioma) for nonhigh performance aircraft.

Related: Pituitary Tumors

Rotim K, Sajko T, Škoro I, et al.
Complete neurological recovery after surgery for mesencephalic cavernoma: case report.
Acta Clin Croat. 2014; 53(4):494-8 [PubMed] Related Publications
Cavernous malformations are classified as a group of vascular malformations of the central nervous system. Conservative treatment of brainstem cavernomas is accompanied with poor outcome. Surgery ofbrainstem cavernomas still poses a challenge due to the high risk of neurological damage and respectable morbidity. We report a case of complete neurological recovery in a 24-year-old female patient with mesencephalic cavernoma treated surgically. This case highlights that careful microsurgical treatment with the goal of complete cavernoma excision remains the treatment of choice in cases with de novo or recurrent hemorrhage. Intraoperative neurophysiologic monitoring should be used as the gold standard during brainstem cavernoma operations in order to avoid nuclear and long tract damages.

Morina A, Kelmendi F, Morina Q, Morina D
Cerebellar dermoid cyst with contrast enhancement mural nodule: case report.
Acta Clin Croat. 2014; 53(4):479-82 [PubMed] Related Publications
Typical dermoid cysts are well-circumscribed fat-density masses with no associated contrast enhancement; rarely, they may appear hyperattenuating on CT scan. CT hyperattenuating dermoid cyst (CHADC) is very uncommon, with only nine case reports in the literature update, which occurs exclusively in the posterior fossa. CHADC with mural nodule is extremely rare and, to the best of our knowledge, only two cases have been documented previously in the literature. A 49-year-old farmer had a 2-month history of occipital headaches, which were not suggestive of raised intracranial pressure. During the last month, he experienced loss of balance, frequent falls, anorexia and loss of weight. Magnetic resonance imaging (MRI) showed a huge mass from the tentorium to the foramen occipitale magnum with obliteration of the fourth ventricle; the lesion was well circumscribed. We completely removed the tumor and postoperative MRI showed no residual tumor. Epidermoid tumors with enhancing mural nodule on MRI and with hyperattenuating lesion on CT are extremely rare. Dermoid cysts are never associated with edema and extremely rarely cause obstructive hydrocephalus. MRI investigations are mandatory to diagnose these cases. The best curative treatment is total removal of the lesion.

Pedeutour-Braccini Z, Burel-Vandenbos F, Gozé C, et al.
Microfoci of malignant progression in diffuse low-grade gliomas: towards the creation of an intermediate grade in glioma classification?
Virchows Arch. 2015; 466(4):433-44 [PubMed] Related Publications
Low-grade gliomas (GII) inescapably progress to high-grade gliomas (GIII). The duration of this transition is highly variable between patients and reliable predictive markers do not exist. We noticed in a subset of cases of GII, obtained by awake neurosurgery, the presence of microfoci with high cellular density, high vascular density, or minimal endothelial proliferation, which we called GII+. Our aim was to investigate whether these foci display immunohistochemical and molecular characteristics similar to GIII and whether their presence is correlated to poor prognosis. We analyzed cell proliferation, hypoxia, vascularization, and alterations of tumorigenic pathways by immunohistochemistry (Ki-67, CD31, HIF-1-alpha, EGFR, P-AKT, P53, MDM2) and fluorescence in situ hybridization (EGFR, MDM2, PDGFRA) in the hypercellular foci of 16 GII+ cases. We compared overall survival between GII, GII+, and GIII. Ki-67, and CD31 expression was higher in the foci than in the tumor background in all cases. Aberrant expression of protein markers and genomic aberrations were also observed in some foci, distinct from the tumor background. Survival was shorter in GII+ than in GII cases. Our results suggest that these foci are the early histological hallmark of anaplastic transformation, which is supported by molecular aberrations. Our study is the first to demonstrate intratumoral morphological, immunohistochemical, and molecular heterogeneity in resection specimens of GII, the presence of which is correlated to shorter survival. Our findings question the discriminative capacity of the current glioma classification and provide arguments in favor of the creation of a grade intermediate between GII and GIII, to optimize the treatment strategy of GII.

Related: FISH

Mari AR, Shah I, Imran M, Ashraf J
Role of intraoperative ultrasound in achieving complete resection of intra-axial solid brain tumours.
J Pak Med Assoc. 2014; 64(12):1343-7 [PubMed] Related Publications
OBJECTIVES: To determine the frequency of completeness of resection for intra-axial solid brain tumours with the help of intra-operative ultrasound to detect residual brain tumour.
METHODS: The cross-sectional study was conducted at the Department of Neurosurgery, Dow University of Health Sciences and Civil Hospital Karachi, from September 2009 to June 2010 and comprised patients with intra-axial solid brain lesion. During operation following standard craniotomy, multi-plane sonographic examination was performed using intra-operative ultrasound for tumour localisation and calculation of dimension, followed by tumour resection in the standard fashion. At the end of tumour resection ultrasound was again used for the detection of any residual tumour. Results of intra-operative ultrasound were compared with post-operative contrast magnetic resonance imaging.
RESULTS: Of the 39 cases in which intra-operative ultrasound was performed, 32(82.1%) were males and 7(17.9%) were females, with an overall mean age of 42.6±19.7 years. Intra-operative ultrasonography was able to localise and delineate the tumour in all 39 (100%) cases. It showed no residual tumour in 36 (92.3%) cases, but in 3(7.7%) cases residual tumour was detected. Post-operative contrast enhancing magnetic resonance imaging showed no residual tumour in 35(89.7%) cases and in 4(10.3%) cases residual tumour was detected. The frequency of completely resected intra-axial solid brain tumour was 35(89.7%), while in 4(10.3%) cases incomplete resection was observed.
CONCLUSION: The study concluded that intra-operative ultrasonography has an important role in achieving increased frequency of completely resected intra-axial solid brain tumours.

Related: Childhood Brain Tumours Childhood Brain Tumors

Chiarelli M, De Simone M, Gerosa M, et al.
An incidental pulmonary meningioma revealing an intracranial meningioma: primary or secondary lesion?
Ann Thorac Surg. 2015; 99(4):e83-4 [PubMed] Related Publications
A 68-year-old man underwent a resection of the right middle lobe for a solitary lesion detected at computed tomography. The histologic result was suggestive for a pulmonary meningioma. Although the result of a preoperative brain computed tomography scan was negative, magnetic resonance imaging showed a skull-base meningioma. On the basis of the absence of symptoms, we decided to observe the intracranial meningioma. At 3 years of follow-up, the patient was free of recurrence and the cerebral lesion was stable. Primary pulmonary meningioma and benign meningioma metastasis share identical microscopic findings, and only a central nervous system radiologic study allows their distinction. The pulmonary lesion in our patient was classified as a meningioma metastasis.

Brachman DG, Pugh SL, Ashby LS, et al.
Phase 1/2 trials of Temozolomide, Motexafin Gadolinium, and 60-Gy fractionated radiation for newly diagnosed supratentorial glioblastoma multiforme: final results of RTOG 0513.
Int J Radiat Oncol Biol Phys. 2015; 91(5):961-7 [PubMed] Related Publications
PURPOSE: The purpose of phase 1 was to determine the maximum tolerated dose (MTD) of motexafin gadolinium (MGd) given concurrently with temozolomide (TMZ) and radiation therapy (RT) in patients with newly diagnosed supratentorial glioblastoma multiforme (GBM). Phase 2 determined whether this combination improved overall survival (OS) and progression-free survival (PFS) in GBM recursive partitioning analysis class III to V patients compared to therapies for recently published historical controls.
METHODS AND MATERIALS: Dose escalation in phase 1 progressed through 3 cohorts until 2 of 6 patients experienced dose-limiting toxicity or a dose of 5 mg/kg was reached. Once MTD was established, a 1-sided 1-sample log-rank test at significance level of .1 had 85% power to detect a median survival difference (13.69 vs 18.48 months) with 60 deaths over a 12-month accrual period and an additional 18 months of follow-up. OS and PFS were estimated using the Kaplan-Meier method.
RESULTS: In phase 1, 24 patients were enrolled. The MTD established was 5 mg/kg, given intravenously 5 days a week for the first 10 RT fractions, then 3 times a week for the duration of RT. The 7 patients enrolled in the third dose level and the 94 enrolled in phase 2 received this dose. Of these 101 patients, 87 were eligible and evaluable. Median survival time was 15.6 months (95% confidence interval [CI]: 12.9-17.6 months), not significantly different from that of the historical control (P=.36). Median PFS was 7.6 months (95% CI: 5.7-9.6 months). One patient (1%) experienced a grade 5 adverse event possibly related to therapy during the concurrent phase, and none experience toxicity during adjuvant TMZ therapy.
CONCLUSIONS: Treatment was well tolerated, but median OS did not reach improvement specified by protocol compared to historical control, indicating that the combination of standard RT with TMZ and MGd did not achieve a significant survival advantage.

Related: Dacarbazine Temozolomide

Alam MS, Ahsan H, Sajjad Z, et al.
Magnetic resonance spectroscopy of enhancing cerebral lesions: analysis of 78 histopathology proven cases.
J Pak Med Assoc. 2014; 64(10):1141-5 [PubMed] Related Publications
OBJECTIVES: To investigate the efficacy of magnetic resonance spectroscopy in differentiating various types of neoplastic and non-neoplastic enhancing cerebral lesions.
METHODS: The prospective study was conducted from January 2007 to December 2009 at the Department of Radiology, Aga Khan University Hospital, Karachi. All patients with enhancing brain lesions on magnetic resonance imaging who underwent magnetic resonance spectroscopy and a biopsy with histopathological analysis were included in study. The lesions were categorised into neoplastic and non-neoplastic lesions on the basis of spectroscopy findings. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of magnetic resonance spectroscopy were calculated. Predicted probabilities were computed and comparison of median values of metabolites and their ratios was analysed using non-parametric Mann Whitney U test to differentiate between neoplastic and non-neoplastic lesions.
RESULTS: Of the 102 patients enrolled, 78 (76.5%) comprised the final study sample. There were 53 (68%) male and 25 (32%) female patients with an overall mean age of 40.21 ± 17.69 years (range: 4-76 years). The mean overall size of the lesion was 4.01 ± 1.79 cm, and 61(78%) lesions were neoplastic and 17 (22%) were non-neoplastic. The sensitivity, specificity, positive predictive value and negative predictive value and diagnostic accuracy of magnetic resonance spectroscopy in differentiating neoplastic and non-neoplastic lesions were 90.16%, 64.70%, 90.16%, 64.70% and 78.20% respectively. A cut-off value of 2.55 of Choline/N-Acetyl Aspartate ratio depicted sensitivity of 70% in differentiating the lesions.
CONCLUSION: Magnetic resonance spectroscopy is a highly sensitive technique in addition to conventional magnetic resonance imaging in characterising and differentiating between neoplastic and non-neoplastic cerebral lesions.

Related: Childhood Brain Tumours Childhood Brain Tumors

Deutsch MB, Mendez MF
Neurocognitive features distinguishing primary central nervous system lymphoma from other possible causes of rapidly progressive dementia.
Cogn Behav Neurol. 2015; 28(1):1-10 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
OBJECTIVE: Define the neurocognitive features of primary central nervous system lymphoma (PCNSL) presenting with dementia, and compare with other causes of rapidly progressive dementia (RPD).
BACKGROUND: PCNSL can present as an RPD. Differentiating PCNSL from other RPDs is critical because lymphomatous dementia may be reversible, and untreated PCNSL is fatal.
METHODS: We performed a meta-analysis of case reports of dementia from PCNSL (between 1950 and 2013); 20 patients (14 with lymphomatosis cerebri) met our criteria. We compared these patients to a case series of patients with RPD from Creutzfeldt-Jakob disease and other non-PCNSL etiologies (Sala et al, 2012. Alzheimer Dis Assoc Disord. 26:267-271).
RESULTS: Median age was 66 years (range 41 to 81); 70% were men. Time from symptom onset to evaluation was <6 months in 65%. No patients had seizures; 5% had headaches; 45% had non-aphasic speech difficulty. There was significantly more memory impairment in patients with PCNSL than other RPDs and significantly less myoclonus and parkinsonism. Behavioral changes and cerebellar signs were not significantly different. Significantly more patients with PCNSL than other RPDs had white matter changes; significantly fewer had atrophy. Elevated CSF protein and pleocytosis were more frequent in PCNSL; patients with other RPDs tended to have normal CSF±14-3-3 protein.
CONCLUSIONS: Unlike patients with RPD from other causes, those with PCNSL commonly present with impaired memory, apathy, and abnormal speech and gait, without headache, seizure, or myoclonus. White matter changes and CSF abnormalities predominate. Improved clinical awareness of PCNSL can prompt earlier diagnosis and treatment.

Mandong BM, Emmanuel I, Vandi KB, et al.
Secondary brain choriocarcinoma: a case report.
Niger J Med. 2015 Jan-Mar; 24(1):81-3 [PubMed] Related Publications
Choriocarcinoma metastasizes widely. One in every ten choriocarcinoma that leaves its primary site, metastasizes to the brain. This 27 years old patient presented with symptoms of space occupying lesion that was confirmed by CT-SCAN. There was no history of vaginal bleeding and amenorrhoea was concealed by unmarried patient. Chest X-ray was normal. Tumor was excised after craniotomy. Histology of tumor was that of secondary choriocarcinoma. Patient responded excellently to chemotherapy and was well one year after. We strongly recommend a high index of suspicion of choriocarcinoma in management of brain tumors. β-HCG assay should be included in investigation of all patients with intracranial tumors irrespective of sex.

Molitch ME
Endocrinology in pregnancy: management of the pregnant patient with a prolactinoma.
Eur J Endocrinol. 2015; 172(5):R205-13 [PubMed] Related Publications
A woman with a prolactinoma is usually infertile. Dopamine agonists usually restore ovulation and fertility and such treatment generally is preferred over transsphenoidal surgery because of higher efficacy and safety. Cabergoline is usually preferred over bromocriptine because of its better efficacy with fewer adverse effects. Either drug increases the rates of spontaneous abortions, preterm deliveries, multiple births, or congenital malformations over what may be expected. However, the number of pregnancies reporting such experience is about sevenfold greater for bromocriptine. Tumor growth causing significant symptoms and requiring intervention has been reported to occur in 2.4% of those with microadenomas, 21% in those with macroadenomas without prior surgery or irradiation, and 4.7% of those with macroadenomas with prior surgery or irradiation. Visual fields should be assessed periodically during gestation in women with macroadenomas. If significant tumor growth occurs, most patients respond well to reinstitution of the dopamine agonist. Delivery of the baby and placenta can also be considered if the pregnancy is sufficiently advanced. Transsphenoidal debulking of the tumor is rarely necessary.

Related: Pituitary Tumors Breast cancer in pregnancy

Rabade N, Goel N, Goel A
Clival dedifferentiated chordoma: a case report.
Anal Quant Cytopathol Histpathol. 2014; 36(6):330-4 [PubMed] Related Publications
BACKGROUND: Chordoma is a rare, slowly growing tumor arising from notochordal rests and occurring in several anatomical locations with different clinical patterns of presentation. Dedifferentiation or sarcomatous transformation in a chordoma is a known but rarely recorded event.
CASE: We report the case of a 58-year-old man diagnosed with chordoma of the clivus who, over the course of 5 years, showed histological and immunohistochemical evidence of progressive dedifferentiation in the tumor.
CONCLUSION: Sarcomatous transformation in chordomas is seen less frequently in the clival region. A high degree of suspicion and extensive sampling are essential for diagnosis, especially in recurrent tumors.

Huan C, Cui G, Lu C, et al.
Role of Ki-67 in acromegalic patients with hyperprolactinemia: retrospective analysis in 61 Chinese Patients.
Pak J Pharm Sci. 2015; 28(2 Suppl):719-23 [PubMed] Related Publications
To evaluate the specific characteristics in acromegalic patients with hyperprolactinemia by analyzing the differences between patients with different Ki-67 values. Between 2002 and 2010, a set of data on 61 patients undergoing transsphenoidal surgery was available at the Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University. Patients were divided into Ki-67 >3% group and <3% group. A retrospective analysis of clinical, hormonal, immunohistochemical, and imaging was observed in all patients. There were no significant differences in age, gender, tumor size and apoplexy between the two groups. Time interval in Ki-67 ≥3% group was longer than <3% group (P=0.037). Patients in Ki-67 >3% group had a higher rate of invasiveness (P=0.048), higher incidences of diabetes mellitus (P=0.036), coarse facial features (P=0.048), large hands and feet (P=0.003), higher GH levels (P<0.05), higher diabetes insipidus rate (P<0.001), and more frequent recurrence (P=0.011) than Ki-67 <3% group. Patients with higher Ki-67 value harbored longer time interval, more aggressive tumors, more acromegaly manifestations, higher GH level, and higher recurrence than patients with lower Ki-67 value.

Related: MKI67 Pituitary Tumors

Huan C, Cui G, Ren Z
The characteristics of acromegalic patients with hyperprolactinemia and the differences with hyperprolactinemia patients.
Pak J Pharm Sci. 2015; 28(2 Suppl):713-8 [PubMed] Related Publications
A substantial proportion of acromegalic patients have co-existent hyperprolactinaemia. To compare this group of population (AC+HPRL) to those of patients with merely hyperprolactinemia (HPRL), a retrospective analysis of patients was conducted. Data regarding clinical and immunohistochemical features, and outcome for patients were reviewed throughout the follow-up period. Four hundred and twenty-three patients were enrolled, with 329 in patients with HPRL and 94 in patients with AC+HPRL. Patients in the AC+HPRL group had a younger age at diagnosis (38.13 ± 13.31 vs. 41.95 ± 14.70 years; p=0.025) and a higher rate of invasion (p=0.007) than those in the HPRL group. The AC+HPRL group had higher GH levels but relatively lower PRL levels than the HPRL group before and after surgery. The rates of positive staining for GH and PRL in HPRL group were 15.20% and 93.01%, and the rates in AC+HPRL group were 84.04% and 87.23%. Patients with HPRL had a lower recurrence rate compared with patients in AC+HPRL group (p=0.018). Additionally, there were no significant correlations between the mean degree of preoperative GH or PRL and the positive rates of immunostaining (p>0.05, p>0.05). The Ki-67 indexes in HPRL group and AC+HPRL group were 3.07% ± 2.13 and 2.33% ± 1.71, respectively (p=0.001). In conclusion, acromegalic patients with hyperprolactinemia need careful and long-term follow-up following an operation.

Related: Pituitary Tumors

Subirá D, Simó M, Illán J, et al.
Diagnostic and prognostic significance of flow cytometry immunophenotyping in patients with leptomeningeal carcinomatosis.
Clin Exp Metastasis. 2015; 32(4):383-91 [PubMed] Related Publications
Some patients with epithelial-cell cancers develop leptomeningeal carcinomatosis (LC), a severe complication difficult to diagnose and with an adverse prognosis. This study explores the contribution of flow cytometry immunophenotyping (FCI) to the diagnosis and prognosis of LC. Cerebrospinal fluid (CSF) samples from patients diagnosed with LC were studied using FCI. Expression of the epithelial-cell adhesion molecule (EpCAM) was the criterion used to identify the epithelial cells. To test the diagnostic precision, 144 patients (94 diagnosed with LC) were included. The prognostic value of FCI was evaluated in 72 patients diagnosed with LC and eligible for therapy. Compared with cytology, FCI showed greater sensitivity and negative predictive value (79.79 vs. 50%; 68.85 vs. 51.55%, respectively), but lower specificity and positive predictive value (84 vs. 100%; 90.36 vs. 100%, respectively). The multivariate analysis revealed that the percentage of CSF EpCAM+ cells predicted an increased risk of death (HR: 1.012, 95% CI 1.000-1.023; p=0.041). A cut-off value of 8% EpCAM+ cells in the CSF distinguished two groups of patients with statistically significant differences in overall survival (OS) (p=0.018). This cut-off value kept its statistical significance regardless of the absolute CSF cell-count. The FCI study of the CSF improved the sensitivity for diagnosing LC, but refinement of the technique is needed to improve specificity. Furthermore, quantification of CSF EpCAM+ cells was revealed to be an independent prognostic factor for OS in patients with LC eligible for therapy. An 8% cut-off value contributed to predicting clinical evolution before initiation of therapy.

Related: EPCAM

Urakawa H, Tsukushi S, Kozawa E, et al.
Postoperative brain metastases in soft tissue sarcomas.
Clin Exp Metastasis. 2015; 32(4):345-51 [PubMed] Related Publications
Brain metastases (BMs) from soft tissue sarcoma (STS) are rare but lethal. We reviewed 187 consecutive patients with STS treated with definitive surgery in Nagoya University Hospital from 2004 to 2014. There were 10 patients with neurofibromatosis-1 (NF-1). We investigated estimated brain metastasis free survival (BMFS) after surgery and overall survival (OS) after BMs in STS. The factors that affected BMFS were also investigated. Eight of 187 patients (4.3%) developed BM with a median period of 18.2 (range 8.8-42.6) months after surgery. Seven of 8 BM patients had metastases at other sites. Estimated 5 year BMFS rate after surgery was 95.2%, and 3 month OS rate after BM was 25.0%. NF-1 (p<0.0001), histological subtype of MPNST (p=0.008), and primary tumor size≥5 cm (p=0.021) were significantly associated with increasing incidence of BM. In this study, postoperative BMs were common in patients with NF-1, MPNST, and large tumors. Considering the impact of NF-1 on BMFS, careful follow up for BM is necessary for NF-1 patients with metastases at other sites.

Related: Soft Tissue Sarcomas Childhood Soft Tissue Sarcomas Soft Tissue Sarcoma

Lu SS, Kim SJ, Kim N, et al.
Histogram analysis of apparent diffusion coefficient maps for differentiating primary CNS lymphomas from tumefactive demyelinating lesions.
AJR Am J Roentgenol. 2015; 204(4):827-34 [PubMed] Related Publications
OBJECTIVE: This study intended to investigate the usefulness of histogram analysis of apparent diffusion coefficient (ADC) maps for discriminating primary CNS lymphomas (PCNSLs), especially atypical PCNSLs, from tumefactive demyelinating lesions (TDLs).
MATERIALS AND METHODS: Forty-seven patients with PCNSLs and 18 with TDLs were enrolled in our study. Hyperintense lesions seen on T2-weighted images were defined as ROIs after ADC maps were registered to the corresponding T2-weighted image. ADC histograms were calculated from the ROIs containing the entire lesion on every section and on a voxel-by-voxel basis. The ADC histogram parameters were compared among all PCNSLs and TDLs as well as between the subgroup of atypical PCNSLs and TDLs. ROC curves were constructed to evaluate the diagnostic performance of the histogram parameters and to determine the optimum thresholds.
RESULTS: The differences between the PCNSLs and TDLs were found in the minimum ADC values (ADCmin) and in the 5th and 10th percentiles (ADC5% and ADC10%) of the cumulative ADC histograms. However, no statistical significance was found in the mean ADC value or in the ADC value concerning the mode, kurtosis, and skewness. The ADCmin, ADC5%, and ADC10% were also lower in atypical PCNSLs than in TDLs. ADCmin was the best indicator for discriminating atypical PCNSLs from TDLs, with a threshold of 556×10(-6) mm2/s (sensitivity, 81.3 %; specificity, 88.9%).
CONCLUSION: Histogram analysis of ADC maps may help to discriminate PCNSLs from TDLs and may be particularly useful in differentiating atypical PCNSLs from TDLs.

Çavuşoğlu M, Ciliz DS, Duran S, Elverici E
Intramedullary lipoma of the cervico-thoracic spinal cord.
JBR-BTR. 2014 Nov-Dec; 97(6):346-8 [PubMed] Related Publications
Most of the spinal cord lipomas reported in the literature are intradural extramedullary, and true intramedullary lipomas are very rare. We present a case of intramedullary spinal cord lipoma of the cervico-thoracic region with extensions over many spinal segments. Magnetic resonance (MR) examination showed an intramedullary lipoma of the cervico-thoracic spinal cord of both high T1 and T2-weighted signal intensity and suppression on fat saturation sequence. MR imaging assessment is critical in the detection of intramedullary lipomas which may present without any neurological deficit at an early stage. Early diagnosis may lead to prevention of the irreversible deterioration of neurological functions.

Soni A, Ren Z, Hameed O, et al.
Breast cancer subtypes predispose the site of distant metastases.
Am J Clin Pathol. 2015; 143(4):471-8 [PubMed] Related Publications
OBJECTIVES: The distant organs to which breast cancer preferentially metastasizes are of significant clinical importance.
METHODS: We explored the relationship between the clinicopathologic factors and the common sites of distant metastasis in 531 consecutive patients with advanced breast cancer.
RESULTS: Breast cancer subtype as a variable was significantly associated with all five common sites of relapse by multivariate analysis. The luminal tumors were remarkable for their significant bone-seeking phenotype and were less frequently observed in lung, brain, and pleural metastases and less likely to be associated with multiorgan relapse. The HER2 subtype demonstrated a significant liver-homing characteristic. African Americans were significantly less likely to have brain-only metastasis in patients with brain relapse.
CONCLUSIONS: These findings further articulate that breast cancer subtypes differ not only in tumor characteristics but also in their metastatic behavior, thus raising the possibility that this knowledge could potentially be used in determining the appropriate strategy for follow-up of patients with newly diagnosed breast cancer.

Related: Breast Cancer

Jiang L, Zhang C, Wu Y, et al.
67kDa laminin receptor regulates the activation of MAPKs through DUSPs in glioma cell line U251.
J BUON. 2015 Jan-Feb; 20(1):253-60 [PubMed] Related Publications
PURPOSE: All-trans-retinoic-acid (ATRA), the active derivative of vitamin A, is critical in regulating cell cycle as well as inhibiting tumor growth and angiogenesis. It has been used in the clinical treatment of leukemia. 67kDa laminin receptor (67LR), as one of the receptor of laminin, plays an important role in tumor cells invasion, proliferation and metastasis. Current research indicates that 67LR is highly expressed in glioma and is associated with tumor progression. However, the underlying molecular mechanisms, especially the signaling pathways involved, have not been reported yet. Therefore it is of great importance to clarify its downstream targets.
METHODS: The U251 glioma cell line was used in this study. Cell Counting Kit-8 was used in cell proliferation assay. Quantitative real-time PCR (qRT-PCR) was used to determine the transcription level of dual specificity phosphatases (DUSPs). Western blot analysis was used to detect the expression of mitogen activated protein kinases (MAPKs) and phosphorylated MAPKs.
RESULTS: 67LR could influence the transcription of DUSPs and expression of MAPKs. ATRA could enhance the expression of 67LR in U251 cells and this enhancement was dose-dependent. ATRA was able to inhibit the growth of U251 cells.
CONCLUSIONS: ATRA expressed significant therapeutic effect on glioma cells, and 67LR is not the only factor that can influence the proliferation of U251 cells.

Zheng R, Fan R, Wen H, et al.
Dosimetric comparison of intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for cerebral malignant gliomas.
J BUON. 2015 Jan-Feb; 20(1):248-52 [PubMed] Related Publications
PURPOSE: To compare the dose distribution characteristics of tumor target area, normal tissues and organs at risk in patients with malignant gliomas treated with intensity- modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT).
METHODS: Plans of IMRT and 3DCRT were designed for each of the 96 included patients with malignant gliomas. Tumor dose was 60 Gy, and the dose distribution differences between the target area and normal tissues were compared using dose-volume histogram (DVH).
RESULTS: Gross tumor volume (GTV) doses for 95% of the volume in the plans of IMRT and 3DCRT were as follows: 59.82±0.43, 57.68±0.62 Gy (p<0.05); clinical target volume (CTV): 58.16±0.48, 54.47±0.28 Gy (p<0.05); and planning treatment volume (PTV): 57.38±0.74, 54.21±0.48 Gy (p<0.05). The conformal index (CI) values of IMRT and 3DCRT plans were 0.92±0.15 and 0.73±0.12, respectively (p<0.05), whereas the homogeneity index (HI) values variability of IMRT and 3DCRT were 0.78±0.12 and 1.13±0.09 respectively (p<0.05). For normal brain tissues pituitary and optic chiasm, the maximum dose (Dmax) and the mean dose (Dmean) of lens exposure differed significantly between thw two plans (p<0.05).
CONCLUSION: The target dose distribution of IMRT was superior to that of 3DCRT in terms of rationality, uniformity and conformal nature. IMRT may be better in protecting normal tissue and increasing the tumor radiation dose compared with 3DCRT.

Pastuszak Ż, Tomczykiewicz K, Piusińska-Macoch R, et al.
The occurrence of tumors of the central nervous system in a clinical observation.
Pol Merkur Lekarski. 2015; 38(224):88-92 [PubMed] Related Publications
UNLABELLED: Brain tumor is an abnormal growth of cells in central nervous system (CNS). The most common primary brain tumors are: gliomas, meningiomas, pituitary adenomas and craniopharyngiomas. The secondary group are metastatic tumors. About 25% patients with cancers have metastasis to CNS.
AIM: The aim of this study was to evaluate the most common symptoms and localization of brain tumors, time from first symptoms to diagnosis and patients' survival rate.
MATERIALS AND METHODS: In this retrospective study 106 patients with primary and metastatic brain tumors hospitalized in Military Institute of Medicine from 2007 to 2012 year were investigated.
RESULTS: The most common cause of metastases to brain is non-smallcell lung carcinoma. The most frequent symptom of brain tumor is headache but very often patients have seizures, vomits, arms and legs weakness. The mean time of life for patients with gliomas was 9 month and 13 days for patients with brain metastases.
CONCLUSIONS: It occurred that patients with primary and secondary brain tumors lived shorter than it is described in literature. In group of patients with metastases to brain 60% had one or two brain tumors so they could be treated with surgery and prognosis for them was better.

Related: Lung Cancer

Rojiani MV, Ghoshal-Gupta S, Kutiyanawalla A, et al.
TIMP-1 overexpression in lung carcinoma enhances tumor kinetics and angiogenesis in brain metastasis.
J Neuropathol Exp Neurol. 2015; 74(4):293-304 [PubMed] Related Publications
Tissue inhibitors of matrix metalloproteinase (TIMP) orchestrate many biologic activities, including inhibition of matrix metalloproteinase activity, activation of pro-matrix metalloproteinases, and regulation of cell proliferation, angiogenesis, and apoptosis induction. Tissue inhibitors of matrix metalloproteinase can play a protective role during tumor invasion and metastasis, but elevated TIMP messenger RNA levels have also been associated with aggressive cancers and poor clinical outcome. We examined the potential roles of TIMP-1 in H2009 lung adenocarcinoma cells and in cells transfected with a human TIMP-1-overexpressing vector (HB-6 and HB-1). Tumors resulting from the implantation of parental cell lines and transfected HB-1 cells into the brains of nude mice had a typical carcinoma profile, but human TIMP-1-overexpressing tumors showed enhanced tumor kinetics and focally more infiltrative features; vessel density assessed with anti-CD31 immunohistochemistry was also greater within HB-1 tumor implants. Similar effects on HB-6 and HB-1 cells versus parental cell lines and empty vector clones were observed in endothelial cell assays. Anchorage-independent growth and invasion through Matrigel were also increased in TIMP-1-overexpressing cells. Together, these results indicate tumor-promoting functions of TIMP-1 through alterations in angiogenesis, increased tumorigenicity, and invasive behavior. Although matrix metalloproteinase inhibition has been the traditionally identified function of TIMP-1, matrix metalloproteinase-independent interactions may contribute to the growth of metastatic carcinomas in the brain.

Related: Angiogenesis and Cancer TIMP1

Walter AC, Gunderson CC, Vesely SK, et al.
Central nervous system metastasis in gynecologic cancer: symptom management, prognosis and palliative management strategies.
Gynecol Oncol. 2015; 136(3):472-7 [PubMed] Related Publications
INTRODUCTION: CNS metastasis (CNSmet) with gynecologic malignancy (GM) is associated with poor prognosis and symptom burden. Two prognostic indices, the recursive partitioning analysis (RPA) and graded prognostic assessment (GPA), used in other solid tumors to guide intervention options were evaluated among GM patients.
METHODS: Retrospective chart review was performed to identify patients with primary GM diagnosed with CNSmet from 2005-2014. RPA and GPA were applied and evaluated for goodness of fit. Long-term survivors (LTS) were those with survival time from CNSmet ≥9 months.
RESULTS: 35 patients were identified with median age of 62 years (range, 41-78). The majority had ovarian cancer (54%). Median survival was 4.5 months (0.1-25.9), and median time from initial diagnosis was 2.6 years (0-19.6). Presenting symptoms varied but headache (57%) and altered mental status (23%) were most common. 37% had a solitary CNS lesion, 31% had 2-8, and 31% >8. 57% were treated with WBRT, 14% with stereotactic radiosurgery (SRS), and 20% with combinations of treatments, and 2 elected for hospice. 27% (9/33) of the patients were LTS. The GPA was not significantly associated with patient outcome (p=0.46). The RPA predicted time to death (p=.0010).
CONCLUSION: Prognostic indices used to guide therapeutic interventions perform poorly in GM. Detection and aggressive symptom management are critical in maintaining QOL. Multidisciplinary consultation is critical to optimize outcomes and symptom control.

Related: Gynacological Cancers

Yu VY, Nguyen D, Pajonk F, et al.
Incorporating cancer stem cells in radiation therapy treatment response modeling and the implication in glioblastoma multiforme treatment resistance.
Int J Radiat Oncol Biol Phys. 2015; 91(4):866-75 [PubMed] Related Publications
PURPOSE: To perform a preliminary exploration with a simplistic mathematical cancer stem cell (CSC) interaction model to determine whether the tumor-intrinsic heterogeneity and dynamic equilibrium between CSCs and differentiated cancer cells (DCCs) can better explain radiation therapy treatment response with a dual-compartment linear-quadratic (DLQ) model.
METHODS AND MATERIALS: The radiosensitivity parameters of CSCs and DCCs for cancer cell lines including glioblastoma multiforme (GBM), non-small cell lung cancer, melanoma, osteosarcoma, and prostate, cervical, and breast cancer were determined by performing robust least-square fitting using the DLQ model on published clonogenic survival data. Fitting performance was compared with the single-compartment LQ (SLQ) and universal survival curve models. The fitting results were then used in an ordinary differential equation describing the kinetics of DCCs and CSCs in response to 2- to 14.3-Gy fractionated treatments. The total dose to achieve tumor control and the fraction size that achieved the least normal biological equivalent dose were calculated.
RESULTS: Smaller cell survival fitting errors were observed using DLQ, with the exception of melanoma, which had a low α/β = 0.16 in SLQ. Ordinary differential equation simulation indicated lower normal tissue biological equivalent dose to achieve the same tumor control with a hypofractionated approach for 4 cell lines for the DLQ model, in contrast to SLQ, which favored 2 Gy per fraction for all cells except melanoma. The DLQ model indicated greater tumor radioresistance than SLQ, but the radioresistance was overcome by hypofractionation, other than the GBM cells, which responded poorly to all fractionations.
CONCLUSION: The distinct radiosensitivity and dynamics between CSCs and DCCs in radiation therapy response could perhaps be one possible explanation for the heterogeneous intertumor response to hypofractionation and in some cases superior outcome from stereotactic ablative radiation therapy. The DLQ model also predicted the remarkable GBM radioresistance, a result that is highly consistent with clinical observations. The radioresistance putatively stemmed from accelerated DCC regrowth that rapidly restored compartmental equilibrium between CSCs and DCCs.

Related: Bone Cancers Breast Cancer Non-Small Cell Lung Cancer Melanoma Osteosarcoma Prostate Cancer Cervical Cancer

Kundapur V, Ellchuk T, Ahmed S, Gondi V
Risk of hippocampal metastases in small cell lung cancer patients at presentation and after cranial irradiation: a safety profile study for hippocampal sparing during prophylactic or therapeutic cranial irradiation.
Int J Radiat Oncol Biol Phys. 2015; 91(4):781-6 [PubMed] Related Publications
PURPOSE: Neurocognitive impairment (NI) in patients with small cell lung cancer (SCLC) after whole brain radiation treatment (WBRT) is a significant cause of morbidity. Hippocampal avoidance (HA) during WBRT may mitigate or prevent NI in such patients. However, this has not been tested in SCLC patients. The estimated risk of metastases in the HA region (HM) in patients with SCLC at diagnosis or after WBRT is unknown. Our study aimed to determine the risk of HM in patients with SCLC and to assess correlated clinical factors.
METHODS AND MATERIALS: Patients with SCLC who experienced brain metastases (BM) at presentation (de novo) or after WBRT treated at the Saskatoon Cancer Centre between 2005 and 2012 were studied. Relevant neuroimaging was independently reviewed by a neuroradiologist. HM was defined as metastases within 5 mm of the hippocampus. Logistic regression analysis was performed to assess correlation between various clinical variables and HM.
RESULTS: Seventy eligible patients were identified. Of 59 patients presenting with de novo BM, 3 patients (5%, 95% confidence interval [CI]: 0%-10.7%) had HM. Collectively there were 359 (range, 1-33) de novo BM with 3 (0.8%, 95% CI: 0%-1.7%) HM deposits. Twenty patients experienced progression of metastatic disease in the brain after WBRT. Of the 20 patients, only 1 patient (5%, 95% CI: 0%-14.5%) experienced HM. On logistic regression, no factors significantly correlated with HM.
CONCLUSION: The overall incidence of HM before or after WBRT in SCLC patients is low, providing preliminary support for the safety of HA during planned clinical trials of HA-WBRT for SCLC.

Related: Lung Cancer

Sahgal A, Aoyama H, Kocher M, et al.
Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis.
Int J Radiat Oncol Biol Phys. 2015; 91(4):710-7 [PubMed] Related Publications
PURPOSE: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases.
METHOD AND MATERIALS: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm.
RESULTS: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRS alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups.
CONCLUSIONS: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group.

Patel B, Chacko G, Nair S, et al.
Clinicopathological correlates of primary central nervous system lymphoma: experience from a tertiary care center in South India.
Neurol India. 2015 Jan-Feb; 63(1):77-82 [PubMed] Related Publications
BACKGROUND: Primary central nervous system lymphomas (PCNSL) constitute a rare group of extranodal non-Hodgkin's lymphomas (NHLs).
AIM: To study the clinical and immunophenotypic profile of patients with a PCNSL who presented between the years 2000 and 2013 in a tertiary care center in South India.
MATERIALS AND METHODS: This was a retrospective study. Demographic and clinical data were obtained from the clinical case records.
INCLUSION CRITERIA: Cases of PCNSL involving brain.
EXCLUSION CRITERIA: Cases of PCNSL involving the spinal cord, meninges and orbit as well as intravascular large B-cell lymphoma, lymphomas with evidence of systemic disease or secondary lymphomas. Archived slides and tissue blocks were retrieved. All cases had hematoxylin and eosin stained sections and immunohistochemistry for CD20, CD3, and MIB-1. Additional immunohistochemistry was performed for CD10, BCL6, and MUM1 on paraffin blocks with sufficient tissue.
RESULTS: There were a total of 73 cases with the mean age of presentation being 45.9 years (range 8-71 years) and with a male predominance (male: female (M:F) = 2.3:1). Headache was the commonest presenting complaint. The mean duration of symptoms was 10.6 weeks. All patients were immunocompetent. Most tumors were supratentorial in location. Out of 73 cases, 70 presented with a diffuse large B-cell lymphoma (DLBCL), two with a Burkitt's lymphoma, and one with a lymphomatoid granulomatosis. Only 51 of the DLBCL cases had sufficient tissue for additional studies. Non-germinal center was the most common phenotype seen in 65.7% (33/51) of cases. Germinal center B-cell (GCB) phenotype was seen in 18/51 cases (34.3%).
CONCLUSION: DLBCL constituted the majority of PCNSLs and although non-germinal center was the predominant phenotype, more than a third of the cases were of the GCB phenotype. As the germinal center phenotype is known to have a better prognosis, further studies to explore its relevance in the Asian population are indicated.

Related: Non Hodgkin's Lymphoma Childhood Non-Hodgkin's Lymphoma NHL - Molecular Biology

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