Tuesday, January 14, 2014

New target discovered for brain cancer treatment

New target discovered for brain cancer treatment
Neurology News & Neuroscience News from Medical News Today

A new study is giving researchers hope that novel targeted therapies can be developed for glioblastoma multiforme (GBM), the most common and most aggressive form of brain cancer, after demonstrating for the first time that a gene known as melanoma differentiation associated gene-9/syntenin (mda-9/syntenin) is a driving force behind the disease's aggressive and invasive nature.

Original Article: http://www.medicalnewstoday.com/releases/271075.php

Radiation therapy combined with intracerebral administration of carboplatin for the treatment of brain tumors

Radiation therapy combined with intracerebral administration of carboplatin for the treatment of brain tumors
Radiation Oncology

Background: In this study we determined if treatment combining radiation therapy (RT) with intracerebral (i.c.) administration of carboplatin to F98 glioma bearing rats could improve survival over that previously reported by us with a 15 Gy dose (5 Gy x 3) of 6 MV photons. Methods: First, in order to reduce tumor interstitial pressure, a biodistribution study was carried out to determine if pretreatment with dexamethasone alone or in combination with mannitol and furosemide (DMF) would increase carboplatin uptake following convection enhanced delivery (CED). Next, therapy studies were carried out in rats that had received carboplatin either by CED over 30 min (20 mug) or by Alzet pumps over 7 d (84 mug), followed by RT using a LINAC to deliver either 20 Gy (5 Gy x 4) or 15 Gy (7.5 Gy x 2) dose at 6 or 24 hrs after drug administration. Finally, a study was carried out to determine if efficacy could be improved by decreasing the time interval between drug administration and RT. Results: Tumor carboplatin values for D and DMF-treated rats were 9.4 +/-4.4 and 12.4 +/-3.2 mug/g, respectively, which were not significantly different (P = 0.14). The best survival data were obtained by combining pump delivery with 5 Gy x 4 of X-irradiation with a mean survival time (MST) of 107.7 d and a 43% cure rate vs. 83.6 d with CED vs. 30-35 d for RT alone and 24.6 d for untreated controls. Treatment-related mortality was observed when RT was initiated 6 h after CED of carboplatin and RT was started 7 d after tumor implantation. Dividing carboplatin into two 10 mug doses and RT into two 7.5 Gy fractions, administered 24 hrs later, yielded survival data (MST 82.1 d with a 25% cure rate) equivalent to that previously reported with 5 Gy x 3 and 20 mug of carboplatin. Conclusions: Although the best survival data were obtained by pump delivery, CED was highly effective in combination with 20 Gy, or as previously reported, 15 Gy, and the latter would be preferable since it would produce less late tissue effects.

Original Article: http://www.ro-journal.com/content/9/1/25

Monday, January 13, 2014

Improved hippocampal dose with reduced margin radiotherapy for glioblastoma multiforme

Improved hippocampal dose with reduced margin radiotherapy for glioblastoma multiforme
Radiation Oncology

Background: To dosimetrically evaluate the effect of reduced margin radiotherapy on hippocampal dose for glioblastoma multiforme (GBM) patients. Methods: GBM patients enrolled on the Radiation Therapy Oncology Group (RTOG) 0825 trial at our institution were identified. Standard RTOG 0825 expansions were 2 cm + 3-5 mm from the gross tumor volume (GTV) to the clinical tumor volume (CTV) and from the CTV to the planning tumor volume (PTV), respectively. These same patients also had reduced margin tumor volumes generated with 8 mm (GTV to CTV) + 3 mm (CTV to PTV) expansions. Individual plans were created for both standard and reduced margin structures. The dose-volume histograms were statistically compared with a paired, two-tailed Student's t-test with a significance level of p < 0.05. Results: A total of 16 patients were enrolled on RTOG 0825. The reduced margins resulted in statistically significant reductions in hippocampal dose at all evaluated endpoints. The hippocampal Dmax was reduced from a mean of 61.4 Gy to 56.1 Gy (8.7%), D40% was reduced from 49.9 Gy to 36.5 Gy (26.9%), D60% was reduced from 32.7 Gy to 18.7 Gy (42.9%) and the D80% was reduced from 27.3 Gy to 15.3 Gy (44%). Conclusions: The use of reduced margin PTV expansions in the treatment of GBM patients results in significant reductions in hippocampal dose. Though the exact clinical benefit of this reduction is currently unclear, this study does provide support for a future prospective trial evaluating the neurocognitive benefits of reduced margin tumor volumes in the treatment of GBM patients.

Original Article: http://www.ro-journal.com/content/9/1/20

Thursday, January 9, 2014

Researchers target cancer stem cells in malignant brain tumors

Researchers target cancer stem cells in malignant brain tumors
Neurology News & Neuroscience News from Medical News Today

Researchers at the Cedars-Sinai Maxine Dunitz Neurosurgical Institute and Department of Neurosurgery identified immune system targets on cancer stem cells - cells from which malignant brain tumors are believed to originate and regenerate - and created an experimental vaccine to attack them.

Original Article: http://www.medicalnewstoday.com/releases/270853.php

The Tumor Radiobiology of SRS and SBRT: Are More Than the 5 Rs Involved?

The Tumor Radiobiology of SRS and SBRT: Are More Than the 5 Rs Involved?
International Journal of Radiation Oncology * Biology * Physics

Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiation therapy (SABR), are rapidly becoming accepted practice for the radiation therapy of certain tumors. Typically, SRS and SBRT involve the delivery of 1 or a few large-dose fractions of 8 to 30 Gy per fraction: a major paradigm shift from radiation therapy practice over the past 90 years, when, with relatively large amounts of normal tissues receiving high doses, the goal was to maximize tumor response for an acceptable level of normal tissue injury. The development of SRS and SBRT have come about because of technologic advances in image guidance and treatment delivery techniques that enable the delivery of large doses to tumors with reduced margins and high gradients outside the target, thereby minimizing doses to surrounding normal tissues. Because the results obtained with SRS and SBRT have been impressive, they have raised the question whether classic radiobiological modeling, and the linear-quadratic (LQ) model, are appropriate for large doses per fraction. In addition to objections to the LQ model, the possibility of additional biological effects resulting from endothelial cell damage, enhanced tumor immunity, or both have been raised to account for the success of SRS and SBRT. In this review, we conclude that the available preclinical and clinical data do not support a need to change the LQ model or to invoke phenomena over and above the classic 5 Rs of radiobiology and radiation therapy, with the likely exception that for some tumors high doses of irradiation may produce enhanced antitumor immunity. Thus, we suggest that for most tumors, the standard radiobiology concepts of the 5 Rs are sufficient to explain the clinical data, and the excellent results obtained from clinical studies are the result of the much larger biologically effective doses that are delivered with SRS and SBRT.

Original Article: http://www.redjournal.org/article/S0360-3016(13)02860-5/abstract?rss=yes

Monday, January 6, 2014

Re-irradiation in the treatment of patients with cerebral metastases of solid tumors: retrospective analysis

Re-irradiation in the treatment of patients with cerebral metastases of solid tumors: retrospective analysis
Radiation Oncology

Background: Goal of this retrospective analysis was to evaluate the role of repeat whole brain radiotherapy in the palliative care of patients with brain metastases due to solid tumors. Methods: Data regarding demographic data, primary tumor, metastasis, radiotherapy and symptoms were compiled on 134 patients with cerebral metastases that received repeat whole brain radiotherapy (WBRT) in our clinic between 2002 and 2011. Results: The analyzed group consisted of 63 (47%) women and 71 (53%) men with a median age of 57 at the start of re-irradiation. Most frequent primary site was the lung (87%).Sixty patients with lung cancer received the first WBRT prophylactically. At the time of re-WBRT 81% of all patients suffered from additional extracerebral metastases.Time between first and second WBRT was a median of 13.4 months. Full dose for the first WBRT was 30 Gy in 2.0 Gy single dose, for the second 20 Gy in 2.0 Gy single dose.At the start of the Re-WBRT 81 patients (60.4%) had mild, 32 (23.9%) severe neurological symptoms, 21 patients (15.7%) were asymptomatic. The median Karnofsky performance status was 70%. Overall, re-WBRT was tolerated satisfactorily. Main side effects were fatigue, erythema and focal alopecia, 10% of patients discontinued treatment before reaching the planned dose. Median survival was 2.8 months since the end of the re-WBRT with good performance status at the start of the re-irradiation being a key indicator for longer survival.Fifty-two patients (39%) showed a clinical improvement of neurological symptoms after the therapy, 59 patients (44%) remained stable, 23 patients (17%) showed worse symptoms. Conclusions: From this large patient collective we were able to show that re-WBRT can be an important therapeutic option with low rate of acute side effects for patients in adequate general condition.

Original Article: http://www.ro-journal.com/content/9/1/4

Friday, January 3, 2014

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[Review] Use of intraoperative cell-salvage for autologous blood transfusions in metastatic spine tumour surgery: a systematic review

[Review] Use of intraoperative cell-salvage for autologous blood transfusions in metastatic spine tumour surgery: a systematic review
The Lancet Oncology

Metastatic spine tumour surgery (MSTS) and metastatic musculoskeletal tumour surgery (MMTS) are associated with substantial blood loss. Allogeneic blood transfusion is the present method used to replenish this blood. Intraoperative cell salvage (IOCS) is a viable alternative, but is contraindicated in tumour surgery because of the risk of tumour dissemination. Use of IOCS–leucocyte depletion filter (LDF) allows removal of tumour cells from blood salvaged during oncological surgery. However, no reports exist on use of IOCS in MSTS or MMTS.

Original Article: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70245-6/abstract?rss=yes

A call for "negative" outcome studies

A call for "negative" outcome studies
Neurology recent issues

Human nature, being what it is, leads to the pernicious phenomenon in the scientific literature of publication bias. We are much more excited and motivated to report our successes than our failures. This is a particularly troublesome tendency when it comes to clinical trials. Studies that fail to reject the null hypothesis are more likely to languish on in draft form and never get published.



Original Article: http://www.neurology.org/cgi/content/short/82/1/11?rss=1