I have an idea for a future Alpha DaRT rGBM trial, is it possible?
Tumor treating fields (TTFields) therapy is a noninvasive anticancer therapy that selectively targets rapidly dividing cancer cells by delivering continuous low-intensity (∼1-3 V/cm), intermediate-frequency (100-500 kHz) alternating electric fields via noninvasive transducer arrays applied to the skin over the tumor-bearing region. TTFields have been shown to prolong survival in patients with newly diagnosed glioblastoma (ndGBM), leading to its approval by the FDA for ndGBM after surgery and chemoradiotherapy, in addition to adjuvant temozolomide (TMZ).
Although TTFields were initially demonstrated to inhibit cancer cells, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects.
(Combination of abstract PMCID: PMC7884384 and source (1))
My idea for a future rGBM trial is to combine the Alpha DaRT and TTFields treatments (and maybe chemo). As most of you probably know, the alpha radiation emitted during the decay of Radium-224 from Alpha DaRT seeds induces DNA damage, double-strand breaks (DSBs), in nearby tumor cells. Therefore, combining Alpha DaRT with TTFields could theoretically increase the persistence of radiation-induced DNA DSBs by impairing the tumor cell's ability to repair this damage.
When doing research on this idea I found an article published 24 April 2026 with the title:
“Prospective randomized trial of tumor-treating fields with chemoradiation in newly diagnosed glioblastoma” (1). This phase II trial investigated the addition of TTFields (through Optune, a medical device made by Novocure) to standard Temozolomide (TMZ) and radiotherapy (RT).
The evaluable patient groups:
N=20 treated with RT+TMZ+TTFields
N=34 treated with RT+TMZ
Both patient groups received TTFields during the maintenance phase (with a ± 14-days window from TMZ+RT)
The 1-year progression-free survival (PFS12) favored the experimental group (37.5% vs 17.3%, P=.06), with a significantly longer median PFS (9.9 vs 4.1 months, P=.016). Median overall survival favored the experimental group (25.9 vs 16.6 months, P=.308).
The primary endpoint, PFS12, did not reach statistical significance. However, the evaluable cohort did show a significantly longer median PFS.
Treatment was well tolerated, with adverse events similar between groups. Serious Adverse Events (SAE) occurred in 33% of patients in the experimental group and 36% in the control group. Only one SAE (folliculitis) was considered related to TTFields. This suggests that the combination of TTFields with chemoradiation is both feasible and well tolerated, with a favorable safety profile. (1)
Both conventional RT and Alpha DaRT induce radiation-associated DNA damage, including DSBs. There is preclinical evidence that TTFields can interfere with DNA-damage repair (homologous recombination for example (1)) and potentially increase PFS while being feasible and well tolerated. I probably do not need to explain why Alpha DaRTs have advantages over conventional RT, but I’ll summarize anyway;
RT delivers external photon radiation to the tumor, while Alpha DaRT delivers highly localized high-LET (Linear Energy Transfer) alpha radiation directly within the tumor using implanted radioactive sources. Because the Alpha DaRT radiation is denser and high-LET, it creates more complex DNA damage to repair. Thus, the tumor is more likely to be killed by this radiation.
I did not find any glioblastoma research on Alpha DaRT in combination with TTFields. Only Alpha DaRT in combination with TMZ or bevacizumab in human glioblastoma multiforme xenografts (2). I also did not find any mention of the TTFields + DaRT combination anywhere else. I did find a mention of Novocure’s TTFields in an Alpha Tau SEC filing, where it is mentioned as competition (3). So, to my knowledge, the combination of Alpha DaRT and TTFields has not yet been investigated.
In what I’ve written above I mostly talked about DNA-damage repair impairing by TTFields to improve the effectiveness of the Alpha DaRT treatment in glioblastoma. But there are other positive effects TTFields have on tumors that I’m not educated enough to expand on, and this is a long post already. One example is the possibility that TTFields suppresses/delays local recurrence.
I found Optune/TTFields therapy while reading through r/glioblastoma. I am a student and do not have professional knowledge on this subject (yet), so feel free to correct what I’ve written. I tried to write as much as possible by copying text written by actual professionals. But I’ve simplified certain things to make it easier to read and more understandable for people who are not in this field. Research might have been subject to cherry picking. The post was improved with assistance from AI and friends.
My main question is: would this be possible and has it ever been mentioned? If it is theoretically possible and has never been mentioned, who should I email to ask about this at Alpha Tau?
AI (Claude and ChatGPT) also mentioned that combining treatments from two “competing” companies could be a problem, in what way is that true?
(1) Limon D, Bokstein F, Blumenthal DT, Ram Z, Grossman R. Prospective randomized trial of tumor-treating fields with chemoradiation in newly diagnosed glioblastoma. Neuro-Oncology Advances [Internet]. 2026 Jan 1;8(1):vdag106. Available from: https://academic.oup.com/noa/article/8/1/vdag106/8662160
(2) Nishri Y, Vatarescu M, Luz I, Epstein L, Dumančić M, Del Mare S, et al. Diffusing alpha-emitters radiation therapy in combination with temozolomide or bevacizumab in human glioblastoma multiforme xenografts. Frontiers in Oncology [Internet]. 2022 Sep 27;12:888100. Available from: https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.888100/full
