Research News in the Fifth Two-Months of 2023

This is the twenty-second article of the project which aims to periodically (every two months) collect the latest research on possible treatments for glioblastoma multiforme.
Below is the news that we considered most significant. As with the previous articles in the series, each piece of news will be preceded by the original title with a link to the source and followed by a short comment. The criterion with which the news is chosen is always to generally include only news relating to research in the clinical phase, unless the potential of the research for the treatment of glioblastoma is truly remarkable.

Study shows how microdevices can be used to treat brain cancer
Researchers at Brigham and Women’s Hospital have developed a micro-device to improve glioma treatment. Implanted during surgery, the device tests multiple drugs on the tumor in real time, offering personalized treatment options. Phase I studies have shown no adverse effects, making it a promising tool for addressing difficult-to-treat brain tumors such as gliomas and particularly glioblastoma. The device is installed and works during surgery offering information on which drugs work on the patient’s specific tumor and is then removed.

Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: to whom do the results of the trials apply?
Clinical trials, especially randomized phase 3 trials, are essential for evaluating new treatments. For glioblastoma, these studies have strict eligibility criteria, which exclude most patients. This may lead to results that are not applicable to the general patient population. Patients ineligible for these studies often have much worse outcomes, experiencing significantly shorter survival. There is a clear need for a system that includes a broader range of glioblastoma patients to gain a comprehensive understanding of the disease.
The article suggests creating a comprehensive learning system to monitor all glioblastoma patients, collecting real-world data on treatment responses, side effects and survival rates.
The use of contemporary matched control groups, which compare similar patient profiles, could offer clearer information about how treatments work outside of clinical trials.
In conclusion, relying solely on randomized phase 3 trials is not sufficient to understand the complexities of glioblastoma. Moving to a broader research system may help create more personalized treatment strategies. Now this is exactly what the Glioblastoma Navigator aims to do, nothing more, nothing less! We have to hurry up!

Impact of extent of resection on outcome from glioblastoma using the RANO resect group classification system: a retrospective, population-based cohort study
This article describes how the extent of tumor resection affects glioblastoma survival. Notably, if all the tumor is removed during surgery, the 2-year survival probability rises to 40%, compared to only 7.7% for a near-total resection, defined as less than 1 cubic cm of non-tumor removed. This is why it is so urgent to look for the best surgeons and the best neurosurgeries. Specialized centers have a better chance of removing all of the tumor, usually with less collateral damage.

CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020
The US Central Brain Tumor Registry publishes this report every year. Unfortunately, this report shows that the median glioblastoma survival in the United States is still stuck at just 8 months. We have always heard that glioblastoma survival is 18-24 months, but this comes from clinical trials and only about 8% of adult glioblastoma patients participate in clinical trials.

Ruxolitinib Plus Radiation and Temozolomide is Safe and Feasible for High-Grade Glioma
Ruxolitinib targets the JAK/STAT signaling pathway which has been associated with tumor progression and worse outcomes in patients with glioblastoma. The article reports the results of the trial in which Ruxolitinib was combined with radiation alone in unmethylated MGMT patients and combined with temozolomide and radiation in methylated MGMT patients. The overall patient population in the phase I CRUX study had a 1-year overall survival (OS) rate of 77%. In the unmethylated MGMT group, the 1-year OS rate was 62% while in the methylated MGMT group it was 93%.

Network-targeting combination therapy of leptomeningeal glioblastoma using multiple synthetic lethal strategies: a case report 
This is a single case. What is really interesting is the process adopted. An in-depth genetic analysis of the tumor was carried out and all the signaling pathways that drive tumor growth were identified. What is different in this case is that we tried to hit all the pathways simultaneously with a new combination of drugs never tried before. An intra-patient dose escalation technique was used to determine the correct dosage of the drugs. The patient was given a treatment regimen consisting of lomustine, olaparib, digoxin, metformin, and intravenous ascorbate. Two years after the recurrence the patient no longer has neurological deficits and has returned to normal life.

That’s all for this research news issue. Thanks to those who provided feedback on how to improve Glioblastoma Navigator. The development of the new version of the system is already underway.
Good luck from the bottom of my heart and a sincere wish to all those who are fighting against glioblastoma and to their loved ones!