Proton FLASH radiotherapy is feasible, safe, and provides pain relief for cancer patients with bone metastases, according to a first-in-human trial presented at the 2022 ASTRO Annual Meeting.
“FLASH is the delivery of radiotherapeutic doses at dose rates several orders of magnitude higher than those currently used in routine clinical practice,” explained study presenter Emily C. Daugherty, MD, of Cincinnati Children’s Hospital and the University of Cincinnati Proton Therapy Center in Ohio.
“This very short amount of time of exposure led to the observation of relative protection of normal tissues after exposure to single doses of FLASH RT as compared to conventional dose rate radiotherapy.”
Dr Daugherty noted that 1 person had previously received electron FLASH radiotherapy. The FAST-01 trial (ClinicalTrials.gov Identifier: NCT04592887) was conducted to evaluate proton FLASH radiotherapy in 10 patients with cancer. All patients had a life expectancy exceeding 2 months and 1 to 3 painful bone metastases in the extremities.
The patients’ median age was 63 years (range, 27-81) at baseline. Half were men and half women. All patients were non-Hispanic White. Cancer types included lung (n=3), breast (n=2), multiple myeloma (n=2), prostate (n=1), thyroid (n=1), and “other” (n=1).
The patients received 8 Gy in a single fraction delivered at a dose rate of 40 Gy or higher per second via a FLASH-enabled proton therapy system. Proton FLASH delivery allows for delivery deeper than 3 cm and more homogeneous dose distribution, Dr Daugherty explained.
There were no FLASH-related technical issues or delays. The total time on the treatment table was 11-22 minutes for 1 site and 32-33 minutes for 2 sites. The mean time on the treatment table was 15.8 minutes per treated site.
The median follow-up was 4.8 months (range, 2.3-13 months). Overall, 67% of patients experienced pain relief, and 50% experienced complete pain response. In 25% of patients, pain remained stable.
Four patients experienced pain flare. Pain flare was defined as a 2-point or greater increase from baseline pain without a decrease in analgesic intake or a 25% or greater increase in analgesic intake without a decrease in pain score, as well as pain and analgesic use returning to baseline after the flare.
There were no serious adverse events (AEs) related to proton FLASH radiotherapy. Six patients had a total of 12 AEs (11 grade 1 AEs; 1 grade 2 AE). The most common AE was grade 1 hyperpigmentation (n=4). Two patients experienced a fracture during follow-up, but neither was attributed to FLASH.
“The treatment efficacy and toxicity profile [of proton FLASH radiotherapy] are qualitatively comparable to the published literature using conventional dose rate photon radiotherapy, and data collection is ongoing,” Dr Daugherty said.
She added that, in the upcoming FAST-02 trial (ClinicalTrials.gov Identifier: NCT05524064), researchers will assess proton FLASH radiotherapy in patients with painful thoracic bone metastases.
Disclosures: This research was supported by Varian, a Siemens Healthineers Company. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Daugherty EC, Mascia AE, Sertorio MGB, et al. FAST-01: Results of the first-in-human study of proton FLASH radiotherapy. ASTRO 2022. October 23-26, 2022. Abstract 6.