Sunday, October 30, 2011

Valproic acid sensitizes human glioma cells for temozolomide and γ-radiation

Abstract  
Temozolomide (TMZ) is given in addition to radiotherapy in glioma patients, but its interaction with the commonly prescribed antiepileptic drug valproic acid (VPA) is largely unknown. Induction of DNA demethylation by VPA could potentially induce expression of the O6-methylguanine-DNA-methyltransferase (MGMT) protein, causing resistance to TMZ and thereby antagonizing its effect. Therefore, this study investigates the interaction between VPA, TMZ, and γ-radiation. Two glioma cell lines were used that differ in TMZ sensitivity caused by the absence (D384) or presence (T98) of the MGMT protein. VPA was administered before (24/48 h) or after (24 h) single doses of γ-radiation; or, after 24 h, VPA treatment was accompanied by a single dose of TMZ for another 24 h. For trimodal treatment the combination of VPA and TMZ was followed by single doses of γ-radiation. In both cell lines VPA caused enhancement of the radiation response after preincubation (DMF0.2 1.4 and 1.5) but not after postirradiation (DMF0.2 1.1 and 1.0). The combination of VPA and TMZ caused enhanced cytotoxicity (DMF0.2 1.7) in both the TMZ-sensitive cell line (D384) and the TMZ-resistant cell line (T98). The combination of VPA and TMZ caused a significant radiation enhancement (DMF0.2 1.9 and 1.6) that was slightly more effective than that of VPA alone. VPA does not antagonize the cytotoxic effects of TMZ. Preincubation with VPA enhances the effect of both γ-radiation and TMZ, in both a TMZ-sensitive and a TMZ-resistant human glioma cell line. VPA combined with TMZ may lead to further enhancement of the radiation response.

  • Content Type Journal Article
  • Category Laboratory Investigation-Human/Animal Tissue
  • Pages 1-7
  • DOI 10.1007/s11060-011-0725-z
  • Authors
    • Krista A. Van Nifterik, Department of Radiation Oncology, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands
    • Jaap Van den Berg, Department of Radiation Oncology, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands
    • Ben J. Slotman, Department of Radiation Oncology, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands
    • M. Vincent M. Lafleur, Department of Radiation Oncology, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands
    • Peter Sminia, Department of Radiation Oncology, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands
    • Lukas J. A. Stalpers, Department of Radiotherapy, Academic Medical Center, Amsterdam, The Netherlands





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Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcom

Publication year: 2011
Source: European Journal of Cancer, Available online 25 October 2011
Birgit Geoerger, Mark W. Kieran, Stephan Grupp, Danuta Perek, Jill Clancy, ...
PurposeA phase II study of temsirolimus was conducted in children and adolescents with high-grade glioma, neuroblastoma or rhabdomyosarcoma.Patients and methodsTemsirolimus 75 mg/mwas administered once weekly until disease progression or intolerance. Using the Simon 2-stage design, further enrolment in each disease cohort required ⩾2 objective responses within the first 12 weeks for the first 12 evaluable patients (those who received ⩾3 temsirolimus doses).ResultsFifty-two heavily pretreated patients with relapsed (12%) or refractory (88%) disease, median age 8 years (range 1–21 years), were enroled and treated. One patient with neuroblastoma achieved confirmed partial response within the first 12 weeks; thus, none of the 3 cohorts met the criterion for continued enrolment. Disease stabilisation at week 12 was observed in 7 of 17 patients (41%) with high-grade glioma (5 diffuse pontine gliomas, 1 glioblastoma multiforme and 1 anaplastic astrocytoma), 6 of 19 (32%) with neuroblastoma and 1 of 16 (6%) with rhabdomyosarcoma (partial response confirmed at week 18). In the three cohorts, median duration of stable disease or better was 128, 663 and 75 d, respectively. The most common treatment-related adverse events were thrombocytopaenia, hyperlipidaemia and aesthenia. Pharmacokinetic findings were similar to those observed in adults.ConclusionsTemsirolimus administered weekly at the dose of 75 mg/mdid not meet the primary objective efficacy threshold in children with high-grade glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable disease merits further evaluation in combination therapy.





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Presence of chemotherapy-induced toxicity predicts improved survival in patients with localised extr

Publication year: 2011
Source: European Journal of Cancer, Available online 27 October 2011
Anne McTiernan, Rachel C. Jinks, Matthew R. Sydes, Barbara Uscinska, Jane M. Hook, ...
AimChemotherapy-induced toxicity is an independent prognostic indicator in several cancers. We aimed to determine whether toxicity was related to survival and histological response in high-grade localised extremity osteosarcoma. We undertook a retrospective analysis of patients treated within three consecutive randomised controlled trials (RCTs) of the European Osteosarcoma Intergroup.MethodsBetween 1982 and 2002, 533 patients were randomised to six cycles of doxorubicin 75 mg/mand cisplatin 100 mg/m. Toxicity data were collected prospectively and graded according to the World Health Organisation (WHO) criteria. Standard univariate and multivariate models were constructed to examine the relationship between reported toxicity, survival, and histological response.ResultsFive- and 10-year overall survival was 57% (95% confidence interval (CI) 52–61%) and 53% (49–58%), respectively. Grades 3–4 oral mucositis (hazard ratio (HR) 0.51, 95% CI 0.29–0.91), grades 1–2 nausea/vomiting (HR 0.37, 95% CI 0.16–0.85), grades 1–2 thrombocytopenia (HR 0.49, 95% CI 0.27–0.87), good histological response (HR 0.42, 95% CI 0.27–0.65), and distal tumour site (HR 0.45, 95% CI 0.28–0.71) were associated with improved survival in multivariate analysis. The only factors that were independently associated with histological response were older age (odds ratio (OR) 0.18, 95% CI 0.04–0.72) and chondroblastic tumour (OR 0.28, 95% CI 0.10–0.77), both being associated with a significantly lower chance of achieving a good response.ConclusionChemotherapy-induced toxicity predicts survival in patients with localised extremity osteosarcoma. Investigation of the pharmacogenomic mechanisms of constitutional chemosensitivity underlying these observations will present opportunities for personalising treatment and could lead to improved outcomes.





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Saturday, October 29, 2011

A clinical trial of bevacizumab, temozolomide, and radiation for newly diagnosed glioblastoma

Journal of Neurosurgery, Volume 0, Issue 0, Page 1-5, Ahead of Print.
Object The presence of angiogenesis is a hallmark of glioblastoma (GBM). Vascular endothelial growth factor (VEGF), which drives angiogenesis, provides an additional target for conventional therapy. The authors conducted a prospective clinical trial to test the effectiveness of bevacizumab, an inhibitor of VEGF, in newly diagnosed GBM. Methods From 2006 through 2010, 51 eligible patients with newly diagnosed GBM were treated with involved-field radiation therapy and concomitant temozolomide (75 mg/m2 daily for 42 days) along with bevacizumab (10 mg/kg every 2 weeks), starting 29 days after surgery. This was followed by 6 cycles of adjuvant temozolomide therapy (150 mg/m2 on Days 1–7 of a 28-day cycle) with bevacizumab administered at 10 mg/kg on Days 8 and 22 of each 28-day cycle. Results The 6- and 12-month progression-free survival (PFS) rates were 85.1% and 51%, respectively. The 12- and 24-month overall survival (OS) rates were 85.1% and 42.5%, respectively. Grade III/IV toxicities were noted in 10 patients (19.6%). No treatment-related deaths were observed. Asymptomatic intracranial bleeding was noted in 5 patients. Conclusions The addition of bevacizumab to conventional therapy in newly diagnosed GBM appears to improve both PFS and OS in patients with newly diagnosed GBM, with acceptable morbidity. A shift toward diffuse relapse was noted in a significant number of patients. Ongoing Phase III clinical trials will show the true benefit of this antiangiogenic approach.





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Intraspinal primitive neuroectodermal tumor in a man with neurofibromatosis type 1: Case report and

Celene B Mulholland, Garni Barkhoudarian, Marcia E Cornford, Duncan Q McBride

Surgical Neurology International 2011 2(1):155-155

Background: The occurrence of primitive neuroectodermal tumors (PNET) in patients with neurofibromatosis type 1 (NF1) has only been reported in two other cases in English-Language literature. Owing to the rarity of intraspinal PNET and the extremely high gene mutation variability in NF1, there is currently no conclusive evidence to suggest that PNET is associated with NF1. Here, we report a case of intradural PNET in a patient with NF1. Case Description: A 27-year-old male underwent a C1-C3 laminectomy for resection of an intramedullary mass. Histopathology and immunohistopathology analysis was performed. Microscopic examination and immunohistochemical staining indicated the mass was a primitive neuroectodermal tumor. Within 1 month after tumor resection, the patient developed leptomeningeal carcinomatosis. The patient was not a candidate for radiation therapy but underwent palliative systemic chemotherapy. He subsequently developed neutropenia and died 3 months after tumor resection. Conclusion: To our knowledge, this is the first reported intraspinal PNET associated with NF1. Genetic analysis of CNS PNETs suggests a possible correlation, but larger case series are needed to support this theory.





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Familial glioblastoma: A case report of glioblastoma in two brothers and review of literature

Ifeoma Ugonabo, Nader Bassily, Alexandra Beier, Jacky T Yeung, Lynette Hitchcock, Frances De Mattia, Aftab Karim

Surgical Neurology International 2011 2(1):153-153

Background: Gliomas that aggregate in families with history of malignancy may have an inheritable genetic basis. Gliomas can occur in several well known tumor syndromes. However, their occurrence in the absence of these syndromes is quite rare. High-grade gliomas, such as glioblastoma multiforme (GBM), are the most common and most lethal primary cancers of the central nervous system (CNS). Case Description: We present a case of two brothers both diagnosed with GBM. Both siblings underwent biopsy with debulking of the tumors by different surgeons. Only one sibling elected to undergo chemotherapy and radiation. Cytogenetic studies were possible only on one sibling and the tumor specimen revealed multiple chromosomal abnormalities, including triploidies 4, 8, 12, 22 and loss of heterozygosity of 1p, 9p, and 10. Histological samples for both tumors were similar, both revealing increased cellularity consisting of gemistocytic astrocytes, central necrosis, and microvascularization. Conclusion: We present two brothers who display a rare familial relationship in the development of their GBMs. Supplementary and improved genetic studies may allow for specific treatment modalities as certain genetic abnormalities have better response to tailored treatments and carry better prognoses.





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Friday, October 28, 2011

[Correspondence] Pitfalls in the assessment of prognostic factors

Kenneth O'Byrne and colleagues examined whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab for advanced non-small-cell lung cancer. Patients with tumours expressing PTEN who were given chemotherapy plus cetuximab had a median survival of 11·4 months (95% CI 8·6–13·6) versus 6·8 months (5·9–12·7), for those with tumours not expressing PTEN (hazard ratio [HR] 0·80, 95% CI 0·55–1·16, p=0·24). For patients given chemotherapy without cetuximab, the median survival was 11·0 months (9·2–12·6) for patients with tumours expressing PTEN versus 9·3 months (7·6–11·9) for patients with tumours not expressing PTEN (HR 0·77, 0·54–1·10, p=0·16).





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O que é Radiocirurgia ?


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Você lê os posts até o final? pense nisto ao escrever os seus trabalhos científicos.

A quantidade de informação facilmente disponível hoje em dia é muito grande. Além de ser fácil buscar a informação que você precisa, existe uma pletora de informações que chega até você sem que a tenha  necessariamente buscado. Um exemplo desta segunda situação ocorre neste blog, assim como vários outros.  Você vai até a página, diretamente ou via Twitter, Facebook etc., e não sabe exatamente





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Meninges Is Source Of Self-Renewing Stem Cells, Potential For Spinal Cord Injury Treatment

In a study published in STEM CELLS, Italian and Spanish scientists have provided the first evidence to show that meninges, the membrane which envelops the central nervous system, is a potential source of self-renewing stem cells...





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Thursday, October 27, 2011

The CareGiver Oncology Quality of Life questionnaire (CarGOQoL): Development and validation of an in

Publication year: 2011
Source: European Journal of Cancer, Available online 25 October 2011
Patricia Minaya, Karine Baumstarck, Julie Berbis, Anthony Goncalves, Fabrice Barlesi, ...
PurposeThe study objective was to validate a specific quality of life (QoL) questionnaire for caregivers of cancer patients, the CareGiver Oncology Quality of Life questionnaire (CarGOQoL), based on the exclusive points of view of the caregivers.Materials and methodsA 75-item questionnaire generated from content analysis of interviews with caregivers was self-completed by 837 caregivers of cancer patients. In addition to sociodemographic data and patient characteristics, self-reported questionnaires assessing QoL, burden, coping and social support were collected. Psychometric properties combined methods relying on both classical test theory and item response theory.ResultsThe final 29 items selected assessed 10 dimensions: psychological well-being, burden, relationship with health care, administration and finances, coping, physical well-being, self-esteem, leisure time, social support and private life; they were isolated from principal component analysis explaining 73% of the total variance. The missing data and the floor effects were low. Some ceiling effects were found for B (34%). Cronbach's alpha coefficients ranged from 0.72 to 0.89, except private life (PL) (0.55). Unidimensionality of the scales was confirmed by Rasch analyses. Correlations with other instruments confirmed the isolated content and significant links were found with respect to patient's characteristics. Reproducibility and sensitivity to change were found satisfactory.ConclusionThe CarGOQoL could provide a reliable and valid measure of caregivers of cancer patients' QoL which are key-actors in the provision of health care.





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Online information as a decision making aid for cancer patients: Recommendations from the Eurocancer

Publication year: 2011
Source: European Journal of Cancer, Available online 25 October 2011
Carol Maddock, Silvia Camporesi, Ian Lewis, Kafait Ahmad, Richard Sullivan
A pan-European survey was conducted under the auspices of the FP7 Eurocancercoms project during the period September 2010–March 2011. It was designed to broaden public policy understanding of patients' specific needs when seeking online cancer information and aimed to identify gaps in the online cancer information provision across Europe. In this paper we describe the methodology and main findings of the Tenovus survey, and draw some recommendations on the use of online information as a decision making aid for cancer patients and their families, namely: (1) transparency and accountability of the sources of information presented online; (2) accreditation of information by different recognised forms of authority and expertise, i.e. both by health-care professional and by patients/public members belonging to patient advocacy groups; (3) scaling up of information: we envisage a 3-tiered system that would enable patients to access different levels of complexity and volume of information from summary to detailed; (4) embedding of custom search tools and interactive search technologies to allow users to define requirements tailored on their needs and be context-driven; (5) communication across discipline boundaries, as patients' and doctors' online communities have very little or no contact among one another. These recommendations were applied for building the online platform EcancerHub, also under the auspices of the Eurocancercoms project, which by bringing together the different cancer communities seeks to break down traditional information boundaries, and through the interactions produce a surplus knowledge that could aid patients in difficult decision making times.





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Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcom

Publication year: 2011
Source: European Journal of Cancer, Available online 25 October 2011
Birgit Geoerger, Mark W. Kieran, Stephan Grupp, Danuta Perek, Jill Clancy, ...
PurposeA phase II study of temsirolimus was conducted in children and adolescents with high-grade glioma, neuroblastoma or rhabdomyosarcoma.Patients and methodsTemsirolimus 75 mg/mwas administered once weekly until disease progression or intolerance. Using the Simon 2-stage design, further enrolment in each disease cohort required ⩾2 objective responses within the first 12 weeks for the first 12 evaluable patients (those who received ⩾3 temsirolimus doses).ResultsFifty-two heavily pretreated patients with relapsed (12%) or refractory (88%) disease, median age 8 years (range 1–21 years), were enroled and treated. One patient with neuroblastoma achieved confirmed partial response within the first 12 weeks; thus, none of the 3 cohorts met the criterion for continued enrolment. Disease stabilisation at week 12 was observed in 7 of 17 patients (41%) with high-grade glioma (5 diffuse pontine gliomas, 1 glioblastoma multiforme and 1 anaplastic astrocytoma), 6 of 19 (32%) with neuroblastoma and 1 of 16 (6%) with rhabdomyosarcoma (partial response confirmed at week 18). In the three cohorts, median duration of stable disease or better was 128, 663 and 75 d, respectively. The most common treatment-related adverse events were thrombocytopaenia, hyperlipidaemia and aesthenia. Pharmacokinetic findings were similar to those observed in adults.ConclusionsTemsirolimus administered weekly at the dose of 75 mg/mdid not meet the primary objective efficacy threshold in children with high-grade glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable disease merits further evaluation in combination therapy.





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Wednesday, October 26, 2011

Gamma Knife surgery for arteriovenous malformations in children

Journal of Neurosurgery: Pediatrics, Volume 6, Issue 5, Page 426-434, November 2010.

Chun Po Yen, M.D., Stephen J. Monteith, M.D., James H. Nguyen, B.A., Jessica Rainey, B.A., David J. Schlesinger, Ph.D., and Jason P. Sheehan, M.D., Ph.D.

Object

The aim of this study was to evaluate the long-term imaging and clinical outcomes of intracranial arteriovenous malformations (AVMs) in children treated with Gamma Knife surgery (GKS).

Methods

Between 1989 and 2007, 200 patients with AVMs who were 18 years of age or younger were treated at the University of Virginia Health System. Excluding 14 patients who had not reached 2-year follow-up, 186 patients comprised this study. Hemorrhage was the most common presenting symptom leading to the diagnosis of AVMs (71.5%). The mean nidus volume was 3.2 cm3 at the time of GKS, and a mean prescription dose of 21.9 Gy was used.

Results

After initial GKS, 49.5% of patients achieved total angiographic obliteration. Forty-one patients whose AVM nidi remained patent underwent additional GKS. The obliteration rate increased to 58.6% after a second or multiple GKS. Subtotal obliteration was achieved in 9 patients (4.8%). Forty-nine patients (26.3%) still had a patent residual nidus. In 19 patients (10.2%), obliteration was confirmed on MR imaging only. Ten patients had 17 hemorrhages during the follow-up period. The hemorrhage rate was 5.4% within 2 years after GKS and 0.8% between 2 and 5 years. Six patients developed neurological deficits along with the radiation-induced changes. Two patients developed asymptomatic meningiomas 10 and 12 years after GKS. After a mean clinical follow-up of 98 months, less than 4% of patients had difficulty attending school or developing a career.

Conclusions

Gamma Knife surgery offers a reasonable chance of obliteration of an AVM in pediatric patients. The incidence of symptomatic radiation-induced changes is relatively low; however, long-term clinical and imaging follow-up is required to identify delayed cyst formation and secondary tumors.





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Chest X-Ray Screening Does Not Reduce Lung Cancer Mortality

A large study shows that routine chest X-rays do not reduce lung cancer mortality; findings are expected to influence new guidelines on screening for lung cancer.
Medscape Medical News





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Online information as a decision making aid for cancer patients: Recommendations from the Eurocancer

Publication year: 2011
Source: European Journal of Cancer, Available online 25 October 2011
Carol Maddock, Silvia Camporesi, Ian Lewis, Kafait Ahmad, Richard Sullivan
A pan-European survey was conducted under the auspices of the FP7 Eurocancercoms project during the period September 2010–March 2011. It was designed to broaden public policy understanding of patients' specific needs when seeking online cancer information and aimed to identify gaps in the online cancer information provision across Europe. In this paper we describe the methodology and main findings of the Tenovus survey, and draw some recommendations on the use of online information as a decision making aid for cancer patients and their families, namely: (1) transparency and accountability of the sources of information presented online; (2) accreditation of information by different recognised forms of authority and expertise, i.e. both by health-care professional and by patients/public members belonging to patient advocacy groups; (3) scaling up of information: we envisage a 3-tiered system that would enable patients to access different levels of complexity and volume of information from summary to detailed; (4) embedding of custom search tools and interactive search technologies to allow users to define requirements tailored on their needs and be context-driven; (5) communication across discipline boundaries, as patients' and doctors' online communities have very little or no contact among one another. These recommendations were applied for building the online platform EcancerHub, also under the auspices of the Eurocancercoms project, which by bringing together the different cancer communities seeks to break down traditional information boundaries, and through the interactions produce a surplus knowledge that could aid patients in difficult decision making times.





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Rare cancers are not so rare: The rare cancer burden in Europe

Publication year: 2011
Source: European Journal of Cancer, Available online 25 October 2011
Gemma Gatta, Jan Maarten van der Zwan, Paolo G. Casali, Sabine Siesling, Angelo Paolo Dei Tos, ...
PurposeEpidemiologic information on rare cancers is scarce. The project Surveillance of Rare Cancers in Europe (RARECARE) provides estimates of the incidence, prevalence and survival of rare cancers in Europe based on a new and comprehensive list of these diseases.Materials and methodsRARECARE analysed population-based cancer registry (CR) data on European patients diagnosed from 1988 to 2002, with vital status information available up to 31st December 2003 (latest date for which most CRs had verified data). The mean population covered was about 162,000,000. Cancer incidence and survival rates for 1995–2002 and prevalence at 1st January 2003 were estimated.ResultsBased on the RARECARE definition (incidence <6/100,000/year), the estimated annual incidence rate of all rare cancers in Europe was about 108 per 100,000, corresponding to 541,000 new diagnoses annually or 22% of all cancer diagnoses. Five-year relative survival was on average worse for rare cancers (47%) than common cancers (65%). About 4,300,000 patients are living today in the European Union with a diagnosis of a rare cancer, 24% of the total cancer prevalence.ConclusionOur estimates of the rare cancer burden in Europe provide the first indication of the size of the public health problem due to these diseases and constitute a useful base for further research. Centres of excellence for rare cancers or groups of rare cancers could provide the necessary organisational structure and critical mass for carrying out clinical trials and developing alternative approaches to clinical experimentation for these cancers.





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Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcom

Publication year: 2011
Source: European Journal of Cancer, Available online 25 October 2011
Birgit Geoerger, Mark W. Kieran, Stephan Grupp, Danuta Perek, Jill Clancy, ...
PurposeA phase II study of temsirolimus was conducted in children and adolescents with high-grade glioma, neuroblastoma or rhabdomyosarcoma.Patients and methodsTemsirolimus 75 mg/mwas administered once weekly until disease progression or intolerance. Using the Simon 2-stage design, further enrolment in each disease cohort required ⩾2 objective responses within the first 12 weeks for the first 12 evaluable patients (those who received ⩾3 temsirolimus doses).ResultsFifty-two heavily pretreated patients with relapsed (12%) or refractory (88%) disease, median age 8 years (range 1–21 years), were enroled and treated. One patient with neuroblastoma achieved confirmed partial response within the first 12 weeks; thus, none of the 3 cohorts met the criterion for continued enrolment. Disease stabilisation at week 12 was observed in 7 of 17 patients (41%) with high-grade glioma (5 diffuse pontine gliomas, 1 glioblastoma multiforme and 1 anaplastic astrocytoma), 6 of 19 (32%) with neuroblastoma and 1 of 16 (6%) with rhabdomyosarcoma (partial response confirmed at week 18). In the three cohorts, median duration of stable disease or better was 128, 663 and 75 d, respectively. The most common treatment-related adverse events were thrombocytopaenia, hyperlipidaemia and aesthenia. Pharmacokinetic findings were similar to those observed in adults.ConclusionsTemsirolimus administered weekly at the dose of 75 mg/mdid not meet the primary objective efficacy threshold in children with high-grade glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable disease merits further evaluation in combination therapy.





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Tuesday, October 25, 2011

Single brain metastasis: Radiosurgery alone compared with radiosurgery plus up-front whole-brain rad

Abstract

BACKGROUND:

Neurosurgical resection is considered the standard treatment for most patients with a single brain metastasis. However, radiosurgery (RS) is a reasonable alternative. It was demonstrated that whole-brain radiotherapy (WBRT) in addition to RS improves local control of 1-3 brain metastases. Little information is available regarding WBRT in addition to RS for a single lesion.

METHODS:

Data of 63 patients who received RS alone for a single brain metastasis were retrospectively compared with 39 patients treated with WBRT+RS for local control of the treated metastasis, distant intracerebral control, and survival. Seven additional potential prognostic factors were investigated including age, sex, Karnofsky performance score, tumor type, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation.

RESULTS:

The 1-year local control rates were 49% after RS and 77% after WBRT+RS (P = .040). The 1-year distant control rates were 70% and 90%, respectively (P = .08). The 1-year survival rates were 57% and 61%, respectively (P = .47). On multivariate analysis, improved local control was associated with WBRT+RS (risk ratio [RR], 1.95; P = .033) and interval from tumor diagnosis to irradiation >15 months (RR, 1.88; P = .042). Improved distant control was almost associated with WBRT+RS (RR, 2.24; P = .05) and age (RR, 2.20; P = .05). Improved survival was associated with KPS 90-100 (RR, 1.73; P = .040), no extracerebral metastases (RR, 1.88; P = .013), RPA class 1 (RR, 2.06; P = .005), and interval from tumor diagnosis to irradiation >15 months (RR, 1.98; P = .009).

CONCLUSION:

The addition of WBRT to RS was associated with improved local control and distant intracerebral control but not survival. Cancer 2011;. © 2011 American Cancer Society.






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Monday, October 24, 2011

Central nervous system atypical teratoid rhabdoid tumours: The Canadian Paediatric Brain Tumour Cons

Publication year: 2011
Source: European Journal of Cancer, Available online 22 October 2011
L. Lafay-Cousin, C. Hawkins, A.S. Carret, D. Johnston, S. Zelcer, ...
BackgroundAtypical teratoid rhabdoid tumours (ATRT) are aggressive brain tumours mostly occurring in early childhood. Largest published series arise from registries and institutional experiences (1–4). The aim of this report is to provide population-based data to further characterise this rare entity and to delineate prognostic factors.Patients and methodsA national retrospective study of children ⩽18 years diagnosed with a central nervous system (CNS) ATRT between 1995 and 2007 was undertaken. All cases underwent central pathology review.ResultsThere were 50 patients (31 males; median age at diagnosis of 16.7 months). Twelve patients were >36 months. Infratentorial location accounted for 52% of all cases. Nineteen patients (38%) had metastatic disease. Fifteen (30%) underwent gross total resection (GTR). Ten patients (20%) underwent palliation. Among the 40 remaining patients, 22 received conventional chemotherapy and 18 received high dose chemotherapy regimens (HDC); nine received intrathecal chemotherapy and 15 received adjuvant radiation.Thirty of the 40 treated patients relapsed/progressed at a median time of 5.5 months (0–32). The median survival time of the entire cohort was 13.5 months (1–117.5 months).Age, tumour location and metastatic status were not prognostic. Patients with GTR had a better survival (2 years overall survival (OS): 60% ± 12.6 versus 21.7% ± 8.5,p = 0.03). HDC conferred better outcome (2 years OS 47.9% ± 12.1 versus 27.3% ± 9.5,p = 0.036). Upfront radiation did not provide survival benefit. Six of the 12 survivors (50%) did not receive radiation.ConclusionThe outcome of CNS ATRT remains poor. However, the use of HDC provides encouraging results. GTR is a significant prognostic factor. The role of adjuvant radiation remains unclear.





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Cerebral pleomorphic xanthoastrocytoma associated with NF1: an updated review with a rare atypical c

Abstract  
The occurrence of cerebral pleomorphic xanthoastrocytoma (PXA) in individuals with neurofibromatosis type 1 (NF1) is very rare. We present a 10-year-old Nigerian boy with NF1 who was found to harbor a thalamic-lateral ventricular solid mass lesion whose histologic and immunohistochemical findings were in keeping with PXA. We also carried out an updated review of the PXA-NF1 literature and found only eight previous reports of this clinical disease association. These reports have been limited to only certain regions of the world, with none yet reported from Africa, South America, Australia, and Eastern Europe. As far as we know, this might be the first such report from Africa. The case we present, in addition, demonstrated some other unique clinical, radiological, and histopathologic characteristics which have been highlighted in this review.

  • Content Type Journal Article
  • Category Review
  • Pages 1-7
  • DOI 10.1007/s10143-011-0362-1
  • Authors
    • Amos O. Adeleye, Division of Neurological Surgery, Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria
    • Clement A. Okolo, Department of Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria
    • Effiong E. Akang, Department of Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria
    • Adekunle M. Adesina, Department of Pathology, Baylor University College of Medicine, Houston, TX, USA





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Survival outcomes for radiotherapy treatment of epidermoid tumors with malignant transformation

Publication year: 2011
Source: Journal of Clinical Neuroscience, Available online 22 October 2011
Daniel Nagasawa, Andrew Yew, Marko Spasic, Winward Choy, Quinton Gopen, ...
Epidermoid tumors are intracranial lesions that may occasionally undergo malignant transformation. Although surgical resection is the first-line treatment for malignant epidermoids, postoperative radiotherapy has been intermittently reported with favorable findings. Our analysis identified all previously reported patients with malignant epidermoids treated with surgical resection alone or surgery plus radiotherapy to examine the potential role for this adjuvant therapy. Whereas patients treated with surgery only had an overall survival of 6.6 months, those treated with postoperative radiotherapy demonstrated a statistically significant increase in survival to 12.7 months (log-rank test,p < 0.003). Furthermore, the mean dosage of radiation given to this patient population was 52.2 Gy, with no appreciable survival benefit for the utilization of levels of radiation greater than 50 Gy. When determining the management for malignant transformation of epidermoid tumors, the combination of surgical resection and radiotherapy may be associated with improved short-term survival.





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Primary Ewing’s sarcoma affecting the central nervous system: a review and proposed prognostic consi

Publication year: 2011
Source: Journal of Clinical Neuroscience, Available online 22 October 2011
George M. Ibrahim, Aria Fallah, Mehdi Shahideh, Uri Tabori, James T. Rutka
Ewing's sarcoma (ES) is a part of a larger family of round blue cell tumors, which occasionally manifest as osseous or extraosseous lesions adjacent to or within the central nervous system (CNS). While a large body of literature exists on ES of bone, data are lacking on tumors with cranial or spinal components that affect the CNS. Here, we perform a systematic review of the literature and summarize the best available evidence on diagnosis, treatment and outcomes of ES affecting the CNS with emphasis on the breadth of clinical presentations, diagnostic tools and emerging management options for these rare and challenging lesions. We include a review of known prognostic factors and propose several new considerations for prognostication of ES affecting the CNS.





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Sunday, October 23, 2011

Researchers Find Coupling Of Proteins Promotes Glioblastoma Development

Two previously unassociated proteins known to be overly active in a variety of cancers bind together to ignite and sustain malignant brain tumors, a research team led by scientists at The University of Texas MD Anderson Cancer Center reports this week in the journal Cancer Cell...





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Treatment of a supratentorial primitive neuroectodermal tumor using magnetic resonance–guided laser-

Journal of Neurosurgery: Pediatrics, Volume 8, Issue 5, Page 468-475, November 2011.
Supratentorial primitive neuroectodermal tumors (PNETs) are rare tumors that carry a poorer prognosis than those arising from the infratentorial compartment (such as medulloblastoma). The overall prognosis for these patients depends on several factors including the extent of resection, age at diagnosis, CSF dissemination, and site in the supratentorial space. The authors present the first case of a patient with a newly diagnosed supratentorial PNET in which cytoreduction was achieved with MR-guided laser-induced thermal therapy. A 10-year-old girl presented with left-sided facial weakness and a large right thalamic mass extending into the right midbrain. The diagnosis of supratentorial PNET was made after stereotactic biopsy. Therapeutic options for this lesion were limited because of the risks of postoperative neurological deficits with resection. The patient underwent MR-guided laser-induced thermal ablation of her tumor. Under real-time MR thermometry, thermal energy was delivered to the tumor at a core temperature of 90°C for a total of 960 seconds. The patient underwent follow-up MR imaging at regular intervals to evaluate the tumor response to the thermal ablation procedure. Initial postoperative scans showed an increase in the size of the lesion as well as the amount of the associated edema. Both the size of the lesion and the edema stabilized by 1 week and then decreased below preablation levels at the 3-month postsurgical follow-up. There was a slight increase in the size of the lesion and associated edema at the 6-month follow-up scan, presumably due to concomitant radiation she received as part of her postoperative care. The patient tolerated the procedure well and has had resolution of her symptoms since surgery. Further study is needed to assess the role of laser-induced thermal therapy for the treatment of intracranial tumors. As such, it is a promising tool in the neurosurgical armamentarium. Postoperative imaging has shown no evidence of definitive recurrence at the 6-month follow-up period, but longer-term follow-up is required to assess for late recurrence.





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Variation in the BRCA2 gene in a child with medulloblastoma and a family history of breast cancer

Journal of Neurosurgery: Pediatrics, Volume 8, Issue 5, Page 476-478, November 2011.
The fact that BRCA genes operate as tumor suppressors is evident from the genetics of the different human disorders caused by inherited mutations. Germline mutations affecting 1 allele of either BRCA1 or BRCA2 confer susceptibility to different types of cancers such as breast cancer and medulloblastoma. A family with a history of cancer was identified in Eastern Turkey in which one of the family members (a 13-year-old boy) had medulloblastoma. Venous blood was collected from available family members. The BRCA1 and BRCA2 genes were sequenced in the patient with medulloblastoma and the healthy father. An Asn372His homozygous variation was noted in the BRCA2 gene in the patient with medulloblastoma whereas the variation was heterozygous in the healthy father. A biallelic homozygous variation was demonstrated in the BRCA2 gene, which is important in medulloblastoma suppression, and may have caused medulloblastoma formation in the 13-year-old boy. Further investigations in large human populations with medulloblastoma are necessary for further delineation of BRCA gene malfunctions and their relationship to medulloblastoma formation, and to clarify the therapeutic implications of these malfunctions.





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Treatment influencing down-staging in EORTC Melanoma Group sentinel node histological protocol compa

Publication year: 2011
Source: European Journal of Cancer, Available online 22 October 2011
Rikke Riber-Hansen, Nina Hastrup, Ole Clemmensen, Nille Behrendt, Siri Klausen, ...
AimMetastasis size in melanoma sentinel lymph nodes (SLNs) is an emerging prognostic factor. Two European melanoma treatment trials include SLN metastasis diameters as inclusion criteria. Whilst diameter estimates are sensitive to the number of sections examined, the level of this bias is largely unknown. We performed a prospective multicentre study to compare the European Organisation for Research and Treatment of Cancer (EORTC) recommended protocol with a protocol of complete step-sectioning.MethodsOne hundred and thirty-three consecutive SLNs from seven SLN centres were analysed by five central sections 50 μm apart (EORTC Protocol) followed by complete 250 μm step-sectioning.ResultsOverall, 29 patients (21.8%) were SLN-positive. TheEORTC Protocolmissed eight of these metastases (28%), one metastasis measuring less than 0.1 mm in diameter, seven measuring between 0.1 and 1 mm. Complete step-sectioning at 250 μm intervals (Extensive Protocol) missed one metastasis (3%) that measured less than 0.1 mm. Thirteen treatment courses (34%) performed if inclusion was based on theCombined Protocolwould not be performed if assessed by theEORTC Protocol. Thus, 10 patients would be without completion lymph node dissection (EORTC MINITUB study), whilst three patients would not be eligible for anti-CTLA4 trial (EORTC protocol 18071). The corresponding number with theExtensive Protocolwould be three; one patient for the MINITUB registration study and two patients for the anti-CTLA4 study.ConclusionsExamining SLNs by close central sectioning alone (EORTC Protocol) misses a substantial number of metastases and underestimates the maximum metastasis diameter, leading to important changes in patient eligibility for various treatment protocols.





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Central nervous system atypical teratoid rhabdoid tumours: The Canadian Paediatric Brain Tumour Cons

Publication year: 2011
Source: European Journal of Cancer, Available online 22 October 2011
L. Lafay-Cousin, C. Hawkins, A.S. Carret, D. Johnston, S. Zelcer, ...
BackgroundAtypical teratoid rhabdoid tumours (ATRT) are aggressive brain tumours mostly occurring in early childhood. Largest published series arise from registries and institutional experiences (1–4). The aim of this report is to provide population-based data to further characterise this rare entity and to delineate prognostic factors.Patients and methodsA national retrospective study of children ⩽18 years diagnosed with a central nervous system (CNS) ATRT between 1995 and 2007 was undertaken. All cases underwent central pathology review.ResultsThere were 50 patients (31 males; median age at diagnosis of 16.7 months). Twelve patients were >36 months. Infratentorial location accounted for 52% of all cases. Nineteen patients (38%) had metastatic disease. Fifteen (30%) underwent gross total resection (GTR). Ten patients (20%) underwent palliation. Among the 40 remaining patients, 22 received conventional chemotherapy and 18 received high dose chemotherapy regimens (HDC); nine received intrathecal chemotherapy and 15 received adjuvant radiation.Thirty of the 40 treated patients relapsed/progressed at a median time of 5.5 months (0–32). The median survival time of the entire cohort was 13.5 months (1–117.5 months).Age, tumour location and metastatic status were not prognostic. Patients with GTR had a better survival (2 years overall survival (OS): 60% ± 12.6 versus 21.7% ± 8.5,p = 0.03). HDC conferred better outcome (2 years OS 47.9% ± 12.1 versus 27.3% ± 9.5,p = 0.036). Upfront radiation did not provide survival benefit. Six of the 12 survivors (50%) did not receive radiation.ConclusionThe outcome of CNS ATRT remains poor. However, the use of HDC provides encouraging results. GTR is a significant prognostic factor. The role of adjuvant radiation remains unclear.





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Saturday, October 22, 2011

Pathogen Genomics Has Become Dirt Cheap

"The human genome was sequenced, and in the process of moving that forward the technology that was developed was incredible. And because of their efforts in the human genome, that technology is available to folks like us."

Northern Arizona University's Paul Keim at the ScienceWriters2011 conference. The ability to compare genomes is a powerful tool for identifying the origins of a natural disease outbreak or bioterrorism. Keim's team examined the anthrax mailed to victims in the 2001 attacks and determined that it did not come from Iraq.

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Friday, October 21, 2011

Identification of a SOX2-dependent subset of tumor- and sphere-forming glioblastoma cells with a dis

Putative cancer stem cells have been identified in glioblastomas and are associated with radio- and chemo-resistance. Further knowledge about these cells is thus highly warranted for the development of better glioblastoma therapies.

Gene expression analyses of 11 high-grade glioma cultures identified 2 subsets, designated type A and type B cultures. The type A cultures displayed high expression of CXCR4, SOX2, EAAT1, and GFAP and low expression of CNP, PDGFRB, CXCL12, and extracellular matrix proteins. Clinical significance of the 2 types was indicated by the expression of type A– and type B–defining genes in different clinical glioblastoma samples. Classification of glioblastomas with type A– and type B–defining genes generated 2 groups of tumors composed predominantly of the classical, neural, and/or proneural subsets and the mesenchymal subset, respectively. Furthermore, tumors with EGFR mutations were enriched in the group of type A samples. Type A cultures possessed a higher capacity to form xenograft tumors and neurospheres and displayed low or no sensitivity to monotreatment with PDGF- and IGF-1–receptor inhibitors but were efficiently growth inhibited by combination treatment with low doses of these 2 inhibitors. Furthermore, siRNA-induced downregulation of SOX2 reduced sphere formation of type A cultures, decreased expression of type A–defining genes, and conferred sensitivity to monotreatment with PDGF- and IGF-1–receptor inhibitors.

The present study thus describes a tumor- and neurosphere-forming SOX2-dependent subset of glioblastoma cultures characterized by a gene expression signature similar to that of the recently described classical, proneural, and/or neural subsets of glioblastoma. The findings that resistance to PDGF- and IGF-1–receptor inhibitors is related to SOX2 expression and can be overcome by combination treatment should be considered in ongoing efforts to develop novel stem cell–targeting therapies.






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Morbidity and mortality following acoustic neuroma excision in the United States: analysis of racial

Acoustic neuromas present a challenging problem, with the major treatment modalities involving operative excision, stereotactic radiosurgery, observation, and fractionated stereotactic radiotherapy. The morbidity/mortality following excision may differ by patient race. To address this concern, the morbidity of acoustic neuroma excision was assessed on a nationwide level. The Nationwide Inpatient Sample from 1994–2003 was used for analysis. Only patients admitted for acoustic neuroma excision were included (International Classification of Diseases, 9th edition, Clinical Modification = 225.1; primary procedure code = 04.01). Analysis was adjusted for several variables, including patient age, race, sex, primary payer for care, income in ZIP code of residence, surgeon caseload, and hospital caseload. Multivariate analyses revealed that postoperative mortality following acoustic neuroma excision was 0.5%, with adverse discharge disposition of 6.1%. The odds ratio for mortality in African Americans compared with Caucasians was 8.82 (95% confidence interval = 1.85–41.9, P = .006). Patients with high-caseload surgeons (more than 2 excisions/year), private insurance, and younger age had decreased mortality, better discharge disposition, and lower overall morbidity (P < .04). Neither hospital caseload nor median income were predictive factors. African Americans were 9 times more likely to die following surgery than Caucasians over a decade-long analysis. Given the relatively benign natural history of acoustic neuroma and the alarmingly increased mortality rate following surgical excision among older patients, African Americans, and patients receiving care from low-caseload surgeons, acoustic neuromas in these patient populations may be best managed by a more minimally invasive modality such as observation, fractionated stereotactic radiotherapy, or stereotactic radiosurgery.






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Prognostic variables in oligodendroglial tumors: a single-institution study of 95 cases

We analyzed the relationships among clinical variables, histology, 1p/19q status, and outcome in 95 patients with oligodendroglial tumors.

The study enrolled adult patients who underwent first-time surgery for a supratentorial oligodendroglial tumor at Oslo University Hospital, Rikshospitalet. Tumors were: 27 oligodendrogliomas, WHO grade II; 32 oligoastrocytomas, WHO grade II; 16 anaplastic oligodendrogliomas, WHO grade III; 14 anaplastic oligoastrocytomas, WHO grade III; and 6 glioblastomas with a major oligodendroglial component, WHO grade IV. The clinical files were reviewed. Three neuropathologists evaluated the histological slides independently. Loss-of-heterozygosity analysis for 1p and 19q was performed by PCR.

Favorable prognostic factors from univariate analyses included seizures as presenting symptom, female sex, location in the frontal lobe, low WHO grade, classic histology, absence of gemistocytic cells, and combined 1p/19q loss. Solitary 19q loss was a negative prognostic marker. 1p/19q status was of prognostic significance in both tumors with classic and nonclassic oligodendroglial histology. In the multivariate analysis, WHO grade II (P< .001), frontal tumor location (P= .002), and combined 1p/19q loss (P< .001) remained favorable prognostic variables.

Our results suggest that tumor location, WHO grade, and 1p/19q status are important independent variables associated with survival in oligodendroglial tumors. The study suggests that solitary 19q loss is a negative prognostic variable and that 1p/19q loss is associated with prolonged survival also in oligodendroglial tumors without classic histology.






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Stereotactic radiosurgery for benign meningiomas

Abstract  
Meningiomas are the second most common primary tumor of the brain. Surgical resection is the preferred treatment for easily accessible tumors that can be safely removed. However, many tumors arise deep within the skull base making complete surgical resection difficult or impossible. Stereotactic radiosurgery is a highly effective alternative to surgical resection that has been used as a primary therapy for benign meningiomas as well as an adjuvant treatment for residual or recurrent tumors. The 5-year tumor control rates for stereotactic radiosurgery are equivalent to gross-total resection with lower morbidity than surgery, especially for skull base lesions. Additionally, adjuvant treatment of subtotally resected tumors results in tumor control rates equivalent to gross-total resection. Stereotactic radiosurgery has been used extensively for the treatment of small and medium sized skull base meningiomas. This technique has also been applied to large meningiomas and superficial tumors such as convexity and parasagittal meningiomas. However, multiple studies demonstrate that tumor control is decreased for superficial lesions and with increasing tumor size. In addition, radiation toxicity increases with increasing tumor size and superficial location. Based on a thorough review of the literature, stereotactic radiosurgery should be considered the primary treatment for skull base meningiomas with high surgical risk and in cases of superficial meningiomas where surgery is contraindicated.

  • Content Type Journal Article
  • Category Topic Review
  • Pages 1-8
  • DOI 10.1007/s11060-011-0720-4
  • Authors
    • Orin Bloch, Department of Neurological Surgery, University of California San, Francisco, 505 Parnassus Avenue, M779, San Francisco, CA 94143-0112, USA
    • Gurvinder Kaur, Department of Neurological Surgery, University of California San, Francisco, 505 Parnassus Avenue, M779, San Francisco, CA 94143-0112, USA
    • Brian J. Jian, Department of Neurological Surgery, University of California San, Francisco, 505 Parnassus Avenue, M779, San Francisco, CA 94143-0112, USA
    • Andrew T. Parsa, Department of Neurological Surgery, University of California San, Francisco, 505 Parnassus Avenue, M779, San Francisco, CA 94143-0112, USA
    • Igor J. Barani, Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA





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Systematic review of quality of life in the management of vestibular schwannoma

Publication year: 2011
Source: Journal of Clinical Neuroscience, Available online 18 October 2011
Andrew Gauden, Philip Weir, Graeme Hawthorne, Andrew Kaye
Vestibular schwannoma (VS) is a benign tumour arising from the vestibular component of the vestibulocochlear nerve. Treatment protocols range from observation to microsurgical resection (MS) or radiation therapy using focused delivery techniques: either stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). Most reported outcome measures explore medically orientated results such as extent of resection or facial nerve function and do not give any insight into how the initial disease, the treatment or operative complications impinge upon the patient's quality of life (QoL). The primary aim of this review was to appraise the quality of research concerning the measurement of QoL in patients with VS. A systematic review was performed including trials of patients with newly diagnosed VS undergoing MS, SRT/SRS, or observation with a measure of QoL. Only trials of prospective design were included. Excluded trials included participants with recurrent disease or comorbidities, and studies reporting patients with VS in association with neurofibromatosis type 2. Each trial for inclusion was assessed for bias and underwent formal data extraction. Between 1973 and 2010, 47 unique trials were identified with eight trials of prospective design. All included studies were prospective non-randomised, observational convenience sampled trials. No randomised control trials or systematic reviews were identified. The most common QoL measure used was the Short Form Questionnaire (SF-36), although it has not been validated in VS. The included trials suggest that the treatment protocols of MS and SRS/SRT are of equal efficacy with regard to impact on QoL; however, the trials were hetereogenous and suffered from a variety of methodological deficiencies. Given this heterogeneity, no meta-analysis was able to be performed. The available literature on QoL in the treatment of VS suffers from significant methodological weaknesses making it difficult to make any assessment as to the efficacy on QoL of available treatment options for VS. Further well-designed, randomised prospective research is necessary to understand this condition, its effect on QoL and how QoL outcomes may be used alongside clinical indicators in making treatment decisions.





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The therapeutic efficacy of fractionated radiotherapy and gamma-knife radiosurgery for craniopharyng

Publication year: 2011
Source: Journal of Clinical Neuroscience, Available online 19 October 2011
Chiman Jeon, Sejin Kim, Hyung Jin Shin, Do-Hyun Nam, Jung-Il Lee, ...
There is no consensus regarding the optimal timing of radiation treatment (RT) for residual or recurrent craniopharyngioma or the preferred treatment modality between fractionated radiotherapy (FRT) and gamma-knife radiosurgery (GKRS) in terms of morbidity and efficacy. This study aims to clarify the optimal timing of RT for residual or recurrent tumors by analyzing the outcomes of RT as a salvage or adjunctive treatment, and to compare the therapeutic efficacy of FRT and GKRS. Between April 1995 and November 2009, 50 of 129 patients received RT for recurrent or residual tumors. The patients were analyzed for medical data, endocrine outcome, long-term morbidity and mortality rates, recurrence rates, and responses to adjuvant RT and GKRS. Mean progression-free survival was 92.5 months (95% confidence interval, 70.9–114.1 months). Univariate analysis revealed that pre-irradiation tumor volume was closely related to better prognosis (p = 0.01). We found that there was no significant difference in recurrence between patients treated with adjuvant compared to salvage RT (p > 0.05). Although we found no difference in the efficacy of FRT and GKRS, five patients were newly diagnosed with hypopituitarism following RT. We concluded that RT has a very high rate of tumor control after both adjuvant or salvage RT. This study highlights the relative safety and efficacy of FRT and GKRS.





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Masked hyperprolactinemia: Tumor-derived factors inhibiting prolactin secretion caused by pituitary-

Publication year: 2011
Source: Journal of Clinical Neuroscience, Available online 19 October 2011
Yasuyuki Kinoshita, Seiji Hama, Atsushi Tominaga, Kazunori Arita, Kazuhiko Sugiyama, ...
Tumor-induced secondary hyperprolactinemia in patients with non-prolactin (PRL)-secreting pituitary tumors has traditionally been ascribed to pituitary stalk damage. We conducted a retrospective analysis of secondary hyperprolactinemia in 106 patients who underwent surgery for non-PRL-secreting pituitary adenoma. The incidence of hyperprolactinemia was evaluated, and pituitary-stalk damage was assessed radiographically using MRI (size of tumor and extension type) and endocrinologically by monitoring hormonal function using a provocation test. The effect of a tumor-derived intrasellar factor, leukemia inhibitory factor (LIF), on hyperprolactinemia was also investigated. Hyperprolactinemia was observed in 31 of the 106 (29.2%) patients. It was not correlated with either physical stalk compression or endocrinological dysfunction. However, LIF expression was negatively correlated with the incidence of secondary hyperprolactinemia (p < 0.01). Although secondary hyperprolactinemia might be caused by pituitary stalk damage, it is possible that LIF masks the effect.





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Cell Phone Use Not Linked To Brain Cancer, Large Study

In recent years we have seen studies yielding conflicting evidence on links between mobile phone use and risk of developing brain cancer as a result of radiation exposure. Now an update of a large and long-running nationwide study in Denmark concludes there is little evidence of a causal link between cell phone use and brain cancer and other types of central nervous system tumors...





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During Brain Surgery, New Tool Helps Surgeons Remove More Cancer Tissue

Scientists are reporting development and successful initial testing of a new tool that tells whether brain tissue is normal or cancerous while an operation is underway, so that surgeons can remove more of the tumor without removing healthy tissue, improving patients' survival. The report appears in ACS' journal Analytical Chemistry...





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Cell Phones Don't Raise Brain Cancer Risk

One of the largest, longest looks at possible dangers found none, researchers report

HealthDay news image

Source: HealthDay





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Toxicity after radiochemotherapy for glioblastoma using Temozolomide - a retrospective evaluation

Purpose: Retrospective evaluation of toxicity and results after radiochemotherapy for glioblastoma Methods: 46 patients with histopathologically proven glioblastoma received simultaneous radiochemotherapy (RCT). The mean age at the beginning of therapy was 59 years, the mean Karnofsky performance index 80%. 44 patients had been operated on before radiotherapy, two had not. A total dose of 60 Gy was applied in daily single fractions of 2.0 Gy within six weeks, 75mg/m^2/day Temozolomide were given orally during the whole radiotherapy period. Results: A local progression could be diagnosed in 34/46 patients (70%). The median survival time amounted to 13.6 months resulting in one-year and two-year survival probabilities of 48% and 8%, respectively.Radiotherapy could be applied completely in 89% of the patients. Chemotherapy could be completed according to schedule only in 56.5%, the main reason being blood toxicity (50% of the interruptions). Most of those patients suffered from leucopenia and/or thrombopenia grade III and IV CTC (Common toxicity criteria). Further reasons were an unfavourable general health status or a rise of liver enzymes.The mean duration of thrombopenia and leucopenia amounted to 64 and 20 days. In two patients, blood cell counts remained abnormal until death. In two patients we noticed a rise of liver enzymes. In one of these in the healing phase of hepatitis a rise of ASAT and ALAT CTC grade IV was diagnosed. These values normalized after termination of temozolomide medication. One patient died of pneumonia during therapy. Conclusion: Our survival data were well within the range taken from the literature. However, we noticed a considerable frequency and intensity of side effects to bone marrow and liver. These lead to the recommendations that regular examinations of blood cell count and liver enzymes should be performed during therapy and temozolomide should not be applied or application should be terminated according to the criteria given by the manufacturer.





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Stereotactic body radiotherapy for multisite extracranial oligometastases

Abstract

BACKGROUND:

A subset of patients with metastatic cancer in limited organs may benefit from metastasis-directed therapy. The authors investigated whether patients with limited metastases could be safely treated with metastasis-directed radiotherapy.

METHODS:

Patients with 1 to 5 metastatic cancer sites with a life expectancy of >3 months received escalating stereotactic body radiotherapy (SBRT) doses to all known cancer sites. Patients were followed radiographically with CT scans of the chest, abdomen, and pelvis and metabolically with fluorodeoxyglucose-positron emission tomography, 1 month after treatment, and then every 3 months. Acute toxicities were scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0, and late toxicities were scored using the Radiation Therapy Oncology Group late toxicity scoring system.

RESULTS:

Sixty-one patients with 113 metastases were enrolled from November 2004 to November 2009 on a prospective radiation dose escalation study. Median follow-up was 20.9 months. Patients tolerated treatment well; the maximal tolerated dose was not reached in any cohort. Eleven patients (18.3%) have not progressed. One and 2-year progression-free survival are 33.3% (95% confidence interval [CI], 22.8-46.1) and 22.0% (95% CI, 12.8-34.4); 1-year and 2-year overall survival are 81.5% (95% CI, 71.1-91.1) and 56.7% (95% CI, 43.9-68.9). Seventy-two percent of patients whose tumors progressed did so in limited (1-3) metastatic sites.

CONCLUSIONS:

Patients with 1 to 5 metastases can be safely treated to multiple body sites and may benefit from SBRT. Further investigation should focus on patient selection. Cancer 2011;. © 2011 American Cancer Society.






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