In John Grisham’s book The Tumor, he tells a story of the typical clinical pathway and trajectory of a patient diagnosed with glioblastoma (GBM), a devastating brain tumor. Then, he sets the stage for a re-imagination of this patient’s clinical course if focused ultrasound were added to his treatment armamentarium. What this could look like is less suffering, longer life expectancy, and cost savings.

Glioblastoma has a 90% mortality rate within 5 years of diagnosis. This disease has lacked any significant improvement in survival in over 30 years, despite scientific advances in many areas, such as molecular subtyping, tailored chemotherapy regimens, and immunotherapy. The current standard-of-care treatment for GBM includes surgical resection, chemotherapy, and radiation.

Focused ultrasound is an emerging therapeutic technology that has the potential to change the treatment landscape and clinical trajectory for a multitude of diseases and conditions, including GBM. The fascinating thing about focused ultrasound is that scientists and clinicians have discovered that the properties of the ultrasound energy can be manipulated in such a way as to induce a variety of different biological effects and mechanisms of action. The technology was initially designed to thermally ablate tissue, but since that time, more than 20 mechanisms of action have been identified.

In GBM, there are three focused ultrasound mechanisms of action that are being employed as an adjunct or complement to traditional therapies: opening of the blood-brain barrier (BBB), sonodynamic therapy (SDT), and radiation sensitization or enhancement (Figure 1).^1,2

The most clinically advanced of these three focused ultrasound mechanisms is BBB opening, which is currently being investigated in numerous clinical trials that combine this technique with delivery of chemotherapeutic agents.^3–5 Thus far, safety and efficacy have been confirmed, and I am excited to see additional clinical trial results. SDT clinical trials are also underway and have shown promise. Lastly, using focused ultrasound to enhance radiation is being investigated.

There are also a variety of focused ultrasound devices being investigated for use, from MRI-guided to neuronavigation-guided to implantable devices. Each system offers unique benefits and challenges, which continue to be elucidated through ongoing clinical work.

One more promising frontier for focused ultrasound and GBM is liquid biopsy. Just as focused ultrasound plus microbubbles can disrupt the BBB to allow the passage of therapeutics into the tumor, this method also allows for the leakage of tumor biomarkers into the blood from the tumor, enabling enhanced diagnosis and monitoring methodologies for GBM.⁶

While this blog post provides a brief overview of focused ultrasound for GBM, it hopefully conveys that the technology is ripe for helping patients live longer, more comfortable lives. The Focused Ultrasound Foundation is on a mission to engage and convene the scientific and medical communities to make this happen as quickly, safely, and effectively as possible so that the fictional character that Grisham described can become a reality.

Author’s note: The Foundation is also enthusiastic about using this technology in a similar fashion for children with diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG), and this area has experienced significant growth over the past year. To learn more, visit the Foundation’s webpage dedicated to DIPG/DMG.

References

1. Roberts JW, Powlovich L, Sheybani N, LeBlang S. Focused ultrasound for the treatment of glioblastoma. J Neurooncol 2022; 157(2):237–247. doi: 10.1007/s11060-022-03974-0. Epub 2022 Mar 10. PMID: 35267132; PMCID: PMC9021052.
2. Parekh K, LeBlang S, Nazarian J, et al. Past, present and future of focused ultrasound as an adjunct or complement to DIPG/DMG therapy: A consensus of the 2021 FUSF DIPG meeting. Neoplasia 2023; 37:100876. doi: 10.1016/j.neo.2023.100876. Epub 2023 Jan 28. PMID: 36709715; PMCID: PMC9900434.
3. Bunevicius A, McDannold NJ, Golby AJ. Focused ultrasound strategies for brain tumor therapy. Oper Neurosurg 2020; 19:9–18. doi: 10.1093/ons/opz374
4. Mainprize T, Lipsman N, Huang Y, et al. Blood-brain barrier opening in primary brain tumors with non-invasive MR-guided focused ultrasound: a clinical safety and feasibility study. Sci Rep 2019; 9:321. doi: 10.1038/s41598-018-36340-0.
5. Meng Y, Hynynen K, Lipsman N. Applications of focused ultrasound in the brain: From thermoablation to drug delivery. Nat Rev Neurol 2021; 17:7–22. doi: 10.1038/s41582-020-00418-z. 
6. Meng Y, Pople CB, Suppiah S, et al. MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors. Neuro Oncol 2021; 23:1789–1797. doi: 10.1093/neuonc/noab057.

Lauren Powlovich, MD, MBA(c), serves as Associate Chief Medical Officer at the Focused Ultrasound Foundation (FUSF). She brings together key stakeholders and synthesizes and executes cohesive plans to lead initiatives in the advancement of focused ultrasound for several applications including glioblastoma, neurodegenerative disorders, pediatrics, pain management, and sonodynamic therapy. She is a co-leader of the Research and Education Team, which strategizes on the allocation of FUSF’s resources to best position the field for success. Prior to joining the Foundation, Lauren trained as an anesthesiologist, and she has always been passionate about putting patients first. She continues to have that mindset and works hard to ensure that focused ultrasound reaches patients as efficiently and safely as possible.