Improving Glioblastoma Treatment with Imaging, Radiotherapy, Drug Delivery, and Therapeutic Systems

Academic Background

Glioblastoma (GBM) is the most common and aggressive type of brain cancer, with an extremely poor prognosis and a five-year survival rate of less than 10%. Despite decades of extensive research in drug therapy, radiation therapy, and surgery, patients’ survival rates have only slightly improved. The current standard treatment is the Stupp protocol, which involves surgical resection followed by radiotherapy and chemotherapy with temozolomide. However, the Stupp protocol remains a palliative treatment, and almost all patients experience tumor recurrence after treatment. Therefore, finding more effective treatments, particularly through innovations in medical devices to enhance existing therapeutic regimens, has become a focus of current research.

This article aims to explore how improvements in imaging techniques, radiotherapy devices, drug delivery systems, and therapeutic devices can enhance the treatment outcomes of glioblastoma. The focus is on how medical devices can augment the efficacy of the Stupp protocol and how devices that directly target tumors can improve patient prognosis.

Source of the Paper

This article was co-authored by Katarzyna Mnich, Stéphanie Lhomond, Eimear Wallace, Pierre-Jean Le Reste, Abhay Pandit, Eric Chevet, Clare Reidy, Afshin Samali, Garry Duffy, and Adrienne M. Gorman, among others, from various research institutions. These authors are affiliated with the University of Galway in Ireland, the University of Rennes in France, and multiple medical research centers. The paper was published in 2024 in the journal Device, with the DOI 10.1016/j.device.2024.100685.

Key Points of the Paper

1. Application of Imaging Techniques in Surgery

The application of imaging techniques in glioblastoma surgery is crucial. Maximal safe resection is a key step in improving patient prognosis. Existing imaging technologies include multiparametric magnetic resonance imaging (MRI), positron emission tomography (PET), and diffusion tensor imaging (DTI). These techniques help surgeons precisely locate the tumor during surgery, allowing for the removal of as much tumor tissue as possible while preserving normal brain function. For example, MRI with contrast enhancement can reveal tumor morphology and surrounding pathological changes, while PET, using radioactive-labeled amino acids such as 11C-methionine, can detect metabolically active tumor regions.

The article points out that although these imaging techniques are highly effective in preoperative planning, intraoperative brain shifts can lead to inaccuracies in resection. To address this, intraoperative MRI and intraoperative ultrasound techniques have been introduced to monitor tumor location in real-time, further improving resection accuracy. Additionally, fluorescence-guided surgery using fluorescent agents such as 5-aminolevulinic acid (5-ALA) allows for real-time visualization of tumor cells during surgery, thereby increasing the rate of gross total resection.

2. Advances in Radiotherapy Devices

Radiotherapy plays a significant role in glioblastoma treatment. Although radiotherapy alone cannot completely prevent recurrence, its combination with surgery and chemotherapy can significantly extend patient survival. The goal of radiotherapy devices is precise radiation delivery, maximizing tumor destruction while minimizing damage to surrounding healthy tissues. In recent years, technologies such as three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and proton therapy have enabled more accurate targeting of radiation doses to tumor regions.

The article also mentions brachytherapy, which involves the implantation of radioactive sources into the surgical cavity to deliver high-dose radiation directly to the tumor site, reducing damage to normal brain tissue. However, due to technical complexity and potential side effects, the clinical application of this method remains limited.

3. Innovations in Drug Delivery Systems

Drug delivery systems are another critical area in glioblastoma treatment. The presence of the blood-brain barrier (BBB) prevents many chemotherapy drugs from effectively reaching brain tumor sites. To overcome this challenge, researchers have developed various local drug delivery systems, such as Gliadel wafers, drug-eluting microspheres, and nanoparticles. These systems can deliver chemotherapy drugs directly to the tumor site, reducing systemic toxicity and improving treatment efficacy.

For example, Gliadel wafers are biodegradable polymer wafers containing carmustine, which are implanted into the tumor cavity during surgery and release the drug over time. Although Gliadel wafers have shown some efficacy in clinical trials, their side effects and limited clinical application have led to their gradual replacement by the Stupp protocol.

4. Devices for Direct Tumor Treatment

In addition to medical devices that support the treatment process, some devices can directly exert therapeutic effects on tumors. For example, laser interstitial thermal therapy (LITT) uses laser energy to heat the tumor to temperatures above 46°C, killing tumor cells. Additionally, the Optune device employs low-intensity electric fields (tumor-treating fields, TTFields) to disrupt tumor cell mitosis, promoting cell death. These devices have shown some efficacy in clinical trials, but design and cost issues limit their widespread application.

Significance and Value of the Paper

This article comprehensively reviews the current medical devices used in glioblastoma treatment and explores how innovations in these devices can enhance existing therapeutic regimens. The article notes that although the Stupp protocol is the current standard treatment, its efficacy remains limited. Future research directions may include the development of more advanced imaging techniques, drug delivery systems combined with personalized therapy, and nanotechnology devices capable of penetrating the blood-brain barrier.

The highlight of this article lies in its systematic summary of the current applications of medical devices in glioblastoma treatment and its potential directions for future research. By combining multimodal therapies, researchers hope to provide more effective treatment options for glioblastoma patients, thereby improving their prognosis and quality of life.

Other Valuable Information

The article also mentions potential future treatment directions, such as immunotherapy and focused ultrasound systems. These emerging technologies may enhance treatment efficacy by disrupting the blood-brain barrier or activating the immune system. Additionally, the development of novel devices like biodegradable electronic patches offers new possibilities for local drug delivery.

This article provides a comprehensive review of glioblastoma treatment and serves as an important reference for future research and clinical practice.