News & Blog

Brain Tumor Research Highlights: May 2017

See April’s Brain Tumor Research Highlights, here.


Over the years, NBTS has given more than $35 million to brain tumor research projects. We’re very proud of the impact this funding has made in advancing the neuro-oncology field closer to better treatments and ultimately a cure. And while NBTS is currently focused on driving our flagship research projects – like the Defeat GBM Research Collaborative – forward, there also continues to be great scientific research efforts happening in the neuro-oncology field, en masse. This is critical, as no one researcher, one lab, or one institution can cure this disease alone. Below are highlights of some newly published research from the brain tumor scientific and medical community, compiled by NBTS Director of Research & Scientific Policy, Ann Kingston, PhD and NBTS Research Programs Manager, Amanda Bates:


 

Multicenter Phase II Study of Temozolomide and Myeloablative Chemotherapy with Autologous Stem Cell Transplant for Newly Diagnosed Anaplastic Oligodendroglioma: Thomas AA, Abrey LE, Terziev R et al (2017) Neuro Oncol. 2017 May 2. doi: 10.1093/neuonc/nox086. [Epub ahead of print] – Link to paper

Two previous multicenter clinical trials have demonstrated a survival benefit of procarbazine, lomustine, and vincristine (PCV) chemotherapy and radiotherapy (RT) compared with RT alone for anaplastic oligodendroglioma (AO) patients with 1p/19q-codeleted tumors. However, there is significant concern over the long-term neurotoxic effects that RT may have on survivors on quality-of-life. To investigate whether chemotherapy alone can effectively treat patients, the investigators conducted a multicenter phase II study in newly diagnosed AO patients using temozolomide (TMZ) as the initial chemotherapy, followed by a high dose chemotherapy (HDC) thiotepa/busulfan myeloablative regimen and autologous stem cell transplant (ASCT). The objective was to determine whether such a regimen could result in long-term control, potentially delaying or eliminating the need for RT.

Forty-one patients were enrolled onto this trial between August 2005 and November 2012. Twenty-seven men and 14 women, with a median age of 44 years (range 30-66) and median KPS of 90 (range 70-100) were treated. The histology was AO in 36 tumors (87.8%) and AOA in 5 (12.1%). Following TMZ treatment, patients who were eligible underwent myeloablative chemotherapy with thiotepa, busulfan, and infusion of autologous CD34+ stem cells previously harvested from patients’ peripheral blood following G-CSF administration.

The results of the study show that intensive chemotherapy with TMZ followed by HDC-ASCT afforded significant disease control and survival with minimal toxicity in a select population of patients with 1p/19q-codeleted tumors. Among all transplanted patients, the 2-year progression free survival (PFS) was 86% and 5-year PFS was 60%, with no deaths after a median follow-up of 66 months. The treatment was reasonably well tolerated, with no toxic deaths and no harvest failures. The results also indicate that chemotherapy alone is not an appropriate strategy for oligodendroglial tumors without 1p19q codeletion, These findings suggest that such a chemotherapy based treatment strategy could delay the need for radiotherapy and associated toxicities during survivorship

Minimally Invasive Biopsies of Deep-Seated Brain Lesions Using Tubular Retractors Under Exoscopic Visualization: Jackson C, Gallia GL, Chaichana L (2017) J Neurol Surg A Cent Eur Neurosurg. May 8. doi: 10.1055/s-0037-1602698. [Epub ahead of print] – Link to paper

Diagnosing brain lesions is critical for informing treatment decisions. Commonly, burr hole needle biopsies or open biopsies through craniotomies are techniques used to access and collect tissue for diagnosis. However, access to deep-seated brain lesions presents a surgical challenge for collecting tissue and can be associated with significant post-surgical morbidities.

In this study a novel method that provides tissue for diagnoses and molecular analyses was evaluated. The method included a transparent plastic tubular retractor with a diameter that allows for displacement of white matter tracts and an exoscope, or an extracorporeal scope to provide optimum visualization through the transparent retractor system. From January 2013 to September 2016, eleven patients underwent minimally invasive surgery for brain tumor biopsies using image guided navigation and tubular retractors with cannula and exoscopic guidance for deep-seated brain lesions. Specimens were obtained using tumor forceps and/or a side-biting tissue aspiration device. The median tissue volume obtained for analysis was 0.1 cm3.  The locations of the lesions included thalamus (3 cases), optic pathway (2 cases), deep cerebellar nuclei (1 case), centrum semiovale/corpus callosum (4 cases), and multifocal (2 cases). In all cases with tumors, diagnosis and the molecular analyses were conducted successfully.  On postoperative CT, no patients had notable hematomas, malignant edema, new deficits, wound infection, symptomatic stroke, and/or required repeat surgery for more tissue for diagnosis. Further surgical resection of the lesions was not undertaken for any of the patients because either it would not affect the natural history of the presumed disease or surgical morbidity would be too high.

This study identifies a surgical method that provides an alternative to burr hole–based needle biopsies and open craniotomies for obtaining adequate tissue for diagnosis, molecular analysis and tissue banking.

Survival benefit of glioblastoma patients after FDA approval of temozolomide concomitant with radiation and bevacizumab: A population-based study: Zhu, P., Du, X. L., Lu, G, Zhu, J. J. (2017) Oncotarget. doi: 10.18632/oncotarget.17054link to paper

Few studies have looked at real-world patient data to determine the benefits of current standard of care (i.e. radiotherapy and concomitant temozolomide [TMZ] followed by adjuvant TMZ for newly diagnosed GBM patients and bevacizumab [BEV] for recurrent GBM), since the time of their regulatory approval. The authors of this study looked at median overall survival of a total of 28,933 GBM patients from January 2000 through December 2013. Patients were divided into three groups based on date of diagnosis. These groups were selected to coincide with the periods before FDA approval of TMZ (1/2000–2/2005), after TMZ approval (3/2005–4/2009), and following FDA approval of BEV (5/2009–12/2013). The aim of the study was to determine if there were statistically significant changes in median overall survival associated with the treatment approvals.

Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) and Texas Cancer Registry (TCR) databases. Data from each database was analyzed individually and as a combined dataset. These databases do not have individual chemotherapy information for each patient, so the researchers relied on the assumption that the newly approved treatments would be implemented by most clinicians shortly after FDA approval. This assumption has been shown to be reasonable by previous studies. These datasets also do not include information on the specific cause of death, which may affect overall survival calculations.

The study shows that using retrospective data analysis, overall survival for GBM patients was significantly improved over the calendar period of diagnosis from January 2000 to December 2013 with median OS of 8 months in 2000-2005 which extended to a median OS of 11 months in 2009-2013.  The researchers considered a number of factors that may influence the survival patterns and concluded that the improved survival was likely attributable to the 2005 approval of TMZ as part of standard of care for newly diagnosed patients and to the subsequent approval of BEV in 2009 for treating recurrent GBM.

Combination of Optune™ with Standard of Care Chemotherapy, Temozolomide, Delayed Decline in Several Health-Related Quality of Life Scales Compared to Temozolomide Alone for Newly Diagnosed Glioblastoma Patients: (2017) – link to press release

Novocure’s Optune™ is a tumor treating field device that uses low frequency alternating electric fields believed to help disrupt cell division in tumor cells. The device has been approved for use in newly diagnosed and recurrent glioblastoma GBM patients. Early in May, at the World Federation of Neuro-oncology Societies 5th Quadrennial meeting, Novocure announced the health-related quality of life outcomes from the EF-14 trial. GBM patients, completed two validated health-related quality of life questionnaires (EORTC QLQ-C30 and BN20), at the beginning of the trial, and every three months thereafter. The study results suggest that Optune™ did not have a negative impact on quality of life, and that deterioration in quality of life was delayed, except for the side effect of itchy skin, for patients using the device. The researchers concluded that Optune and temozolomide provided stability or improvement in the quality of life for GBM patients compared to the use of temozolomide alone.


If you want to help fund research for new and better treatments for brain tumors – and ultimately a cure – please consider making a gift here.

*Cover photo courtesy of the National Cancer Institute’s (NCI) website (www.cancer.gov)
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