The concomitant use of the tumor therapy, radiotherapy and temozolomide fields is being investigated as a potential treatment for patients with newly diagnosed stage IV glioblastoma.
The simultaneous use of tumor therapy, radiotherapy and temozolomide fields is being investigated as a potential treatment for patients with newly diagnosed stage IV glioblastoma (GBM), explained Wenyin Shi, MD, PhD, in an interview with OncLiveÂ® before the 10th Annual Brain Tumor Symposium.
âAt the next Brain Tumor Symposium, we will be discussing clinical trial developments in Jefferson, with a focus on GBM. The main topic we will be discussing is a researcher-initiated trial conducted by our group, which is studying the combination of tumor treatment fields with radiation therapy for patients with newly diagnosed GBM, âsaid Shi, Professor and Co-Director of the Brain Tumor Center at the Sidney Kimmel Cancer Center and co-director of the stereotaxic radiosurgery program at Jefferson University Hospitals of Jefferson Health. We will also discuss a trial in development, focusing on thermal radiation treatment. [with] brachytherapy for recurrent GBM.
In the interview, Shi discussed new techniques in radiation therapy and tumor treatment in glioblastoma and clinical trial updates at Jefferson ahead of the annual meeting.
OncLiveÂ®: What is the basis for evaluating the fields of tumor treatment and radiation therapy in patients with newly diagnosed GBM?
Shi: GBM is the most threatening brain cancer in adults, with very low overall survival [OS]. Progress in the management of GBM has been slow, failing to meet the needs of patients and their families. More recently, a phase 3 randomized trial introduced a new treatment device, the tumor treatment fields in the management of GBM. Based on EF-14 test [NCT00916409], patients who used tumor treatment drapes experienced improvement in OS of nearly 5 months. Treatment is currently used when patients complete radiation therapy and the concomitant temozolomide.
However, there is ample preclinical evidence to suggest that the fields of tumor treatment and radiation therapy have synergistic effects. Our group therefore initiated a trial to assess the feasibility and preliminary efficacy of combining the fields of tumor treatment and radiotherapy for patients with newly diagnosed GBM. We will recruit adult patients with newly diagnosed GBM who have a performance index above 60.
What did the preliminary results show?
The trial we conducted and completed a trial that combines fields of tumor treatment with concomitant radiotherapy, and enrolled 30 patients. Our preliminary data indicate that progression-free survival is 9.3 months, which is significantly higher than historical controls, which range from 5.2 months to 7.1 months.
Another trial by a group of Israeli researchers provided evidence of feasibility and tolerability to support this concomitant regimen. Currently, this new approach of combining the fields of tumor treatment with radiotherapy is being tested in a phase 3 randomized trial led by Novocure, which is the TRIDENT trial. The randomized phase 3 trial involving 950 patients is an international trial expected to open in more than 150 sites worldwide. The trial is currently activated in the United States, Israel and countries in southern Europe. The experimental regimen is exactly what we developed in the original study using simultaneous radiochemotherapy with tumor treatment fields.
Regarding the second trial, how could heat therapy work in synergy with local brachytherapy?
GBM has a local recurrence model. Over 90% of tumors will recur at the primary sites, so local therapy has always been the focus of treatment for GBM. Previous studies have focused on accelerating the dose of radiation therapy. Unfortunately, this did not lead to an improvement [in outcomes]. Some studies conducted by the University of California, San Francisco have shown that if we use heat therapy with topical brachyradiation therapy, it can improve OS in patients with GBM.
With this new technology, we are using a very new nanoparticle that can produce heat therapy and combine a device built and developed by our group using high dose radiation therapy in the resection cavity while simultaneously delivering heat therapy to patients with recurrent disease. The study is currently in the preclinical phase; we are doing animal studies and we plan to open the phase 2 study soon.
What are you expecting to see at the symposium?
It is a very exciting time for the management of the GBM and, more recently, for the World Health Organization. [WHO] classification for GBM has undergone an iteration. We are entering an advanced molecular realm. Since the previous WHO classification, we were already using molecular advice for the diagnosis and treatment of GBM patients, but now it’s really prime time and it’s dramatically changing our pattern of diagnosis and management. I am delighted to discuss new developments and [hear from] keynote speakers on new developments and different management strategies for patients with