Scientists create imaging ‘toolkit’ to help identify new brain tumor drug targets

Breckwoldt, M. et al. Correlated magnetic resonance imaging and ultramicroscopy (MR-UM) is a tool kit to assess the dynamics of glioma angiogenesis. eLife, 2016; 5

160202090702_1_540x360

Brain tumor vascularisation is visualized using T2*-weighted magnetic resonance imaging.
Credit: Breckwoldt, Bode et al.

Stopping the growth of blood vessels in tumors is a key target for glioblastoma therapies, and imaging methods are essential for initial diagnosis and monitoring the effects of treatments. A team of researchers has developed a combined magnetic resonance imaging (MRI) and ultramicroscopy ‘toolkit’ to study vessel growth in glioma models in more detail than previously possible.

In their study in mice, the team combined an MRI approach in vivo with ultramicroscopy of ex vivo whole brains cleared for imaging.

The technique is based on T2*-weighted (T2*-w) MRI images, one of the basic pulse sequences in MRI, with high resolution to allow for substantially more detail than conventional T2*-w imaging. Pre- and post-contrast MR scans were performed to define the growth of vessels during glioma development in two different glioma models.

The team further mapped the development of vessels by dual-colour ultramicroscopy of whole, cleared brains. Using fluorescent labelling of microvessels, they collected complementary 3D MR and ultramicroscopy data sets (dubbed the ‘MR-UM’), which could be compared side-by-side.

Read the commentary article via ScienceDaily

Impact of vision loss among survivors of childhood central nervous system astroglial tumors

de Blank, P.M.K. et al. Cancer: Article first published online 11 JAN 2016

eye test.jpg

BACKGROUND: The impact of impaired vision on cognitive and psychosocial outcomes among long-term survivors of childhood low-grade gliomas has not been investigated previously but could inform therapeutic decision making.

METHODS: Data from the Childhood Cancer Survivor Study were used to investigate psychological outcomes (measures of cognitive/emotional function) and socioeconomic outcomes (education, income, employment, marital status, and independent living) among astroglial tumor survivors grouped by 1) vision without impairment, 2) vision with impairment (including unilateral blindness, visual field deficits, and amblyopia), or 3) bilateral blindness. The effect of vision status on outcomes was examined with multivariate logistic regression with adjustments for age, sex, cranial radiation therapy, and medical comorbidities.

 

RESULTS: Among 1233 survivors of childhood astroglial tumors 5 or more years after their diagnosis, 277 (22.5%) had visual impairment. In a multivariate analysis, survivors with bilateral blindness were more likely to be unmarried (adjusted odds ratio (OR), 4.7; 95% confidence interval [CI], 1.5-15.0), live with a caregiver (adjusted OR, 3.1; 95% CI, 1.3-7.5), and be unemployed (adjusted OR, 2.2; 95% CI, 1.1-4.5) in comparison with those without visual impairment. Bilateral blindness had no measurable effect on cognitive or emotional outcomes, and vision with impairment was not significantly associated with any psychological or socioeconomic outcomes.

 

CONCLUSIONS: Adult survivors of childhood astroglial tumors with bilateral blindness were more likely to live unmarried and dependently and to be unemployed. Survivors with visual impairment but some remaining vision did not differ significantly with respect to psychological function and socioeconomic status from those without visual impairment.

 

Read the abstract here

Immunotherapy response assessment in neuro-oncology: a report of the RANO working group

The Lancet Oncology: Volume 16, No. 15, e534–e542, November 2015

Immunotherapy is a promising area of therapy in patients with neuro-oncological malignancies. However, early-phase studies show unique challenges associated with the assessment of radiological changes in response to immunotherapy reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumour regression, can still occur after initial disease progression or after the appearance of new lesions. Refinement of the response assessment criteria for patients with neuro-oncological malignancies undergoing immunotherapy is therefore warranted. Herein, a multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describe immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria based on guidance for the determination of tumour progression outlined by the immune-related response criteria and the RANO working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease within 6 months of initiating immunotherapy, including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for the use of corticosteroids. We review the role of advanced imaging techniques and the role of measurement of clinical benefit endpoints including neurological and immunological functions. The iRANO guidelines put forth in this Review will evolve successively to improve their usefulness as further experience from immunotherapy trials in neuro-oncology accumulate.

Supplementary audio
Immunotherapy response assessment criteria for neuro-oncology: The Lancet Oncology. Hideho Okada discusses immunotherapy response assessment criteria in neuro-oncology.

via Immunotherapy response assessment in neuro-oncology: a report of the RANO working group – The Lancet Oncology.

Tetanus shot improves patient survival with brain tumor immunotherapy

An innovative approach using a tetanus booster to prime the immune system enhances the effect of a vaccine therapy for lethal brain tumors, dramatically improving patient survival, according to a study led by Duke Cancer Institute researchers.

In a small human study, they enrolled 12 brain tumor patients, with half randomly assigned to receive a tetanus booster and the other half a placebo injection. The next day, patients in both groups were then given the dendritic cell immunotherapy. Researchers did not know which therapies the patients received.

Patients randomized to get a tetanus shot showed a significant increase in survival from the time of pre-conditioning compared to patients receiving just the dendritic cell therapy, with half living from 51 to 101 months, compared to 11.6 months for the comparison group. One patient from the tetanus group continues to have no tumor growth and is still alive at eight years after the treatment.

Link to the research: Duane A. Mitchell, et al., Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature, 2015; DOI: 10.1038/nature14320