In a phase II trial reported in The Lancet Oncology, Vora et al found that short-course hypofractionated proton-beam therapy guided by 3,4-dihydroxy-6-[F-18]fluoro-L-phenylalanine (F-18–DOPA) positron-emission tomography (PET) and contrast-enhanced MRI produced good outcomes in patients aged ≥ 65 years with newly diagnosed glioblastoma.
Study Details
In the study, 39 patients (median age = 70.2 years) enrolled at the Phoenix and Rochester Mayo Clinic sites between May 2019 and May 2021 received dose-escalated hypofractionated proton beam therapy at 35- to 40-Gy equivalents in 5 (tumor volume ≤ 65 cm3) or 10 treatments (tumor volume > 65 cm3) plus concurrent temozolomide at 75 mg/m2 daily on days 1 to 7 in the 5-treatment regimen or on days 1 to 14 in the 10-treatment regimen; 1 month after completing radiotherapy, patients received adjuvant temozolomide at 150 to 200 mg/m2 on days 1 to 5 for six 28-day cycles. The primary outcome measure was overall survival at 12 months.
Key Findings
At data cutoff (in January 2024), median follow-up was 25.4 months (interquartile range = 22.1–29.7 months). Among the 39 patients, 22 (56%, 95% confidence interval [CI] = 39%–72%) were alive at 12 months. Median overall survival was 13.1 months (95% CI = 11.1–19.1 months). As noted by the investigators, the outcomes compared favorably with median overall survival of 6 to 9 months and 12-month survival of 33% observed in historical controls.
At data cutoff, median progression-free survival was 7.1 months (95% CI = 6.0–11.0 months); at 12 months, progression-free survival was 31% (95% CI = 19%–49%).
All patients completed radiotherapy courses with concurrent temozolomide without treatment breaks. Grade 3 treatment-related adverse events occurred in five patients (13%), consisting of CNS necrosis in four (10%) and thrombocytopenia in one (3%). No treatment-related grade 4 or 5 adverse events were observed.
The investigators concluded: “We observed improved overall survival compared with historical controls and a promising adverse event profile by using [F-18–DOPA] PET−guided, dose-escalated, hypofractionated proton beam therapy. These findings have resulted in the opening of a phase 2 study (NCT05781321) investigating this regimen versus standard-of-care treatment in adults of any age with newly diagnosed glioblastoma.”
Sujay A. Vora, MD, of Mayo Clinic, Phoenix, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the Mayo Clinic Marley Endowment Funds and the Lawrence W. and Marilyn W. Matteson Fund in Cancer Research. For full disclosures of the study authors, visit www.thelancet.com.
