Proton therapy reduces toxicity risk vs. IMRT in locally advanced esophageal cancer
Proton beam therapy appeared to reduce the risk for and severity of adverse events compared with intensity-modulated radiation therapy for patients with locally advanced esophageal cancer, according to results of a randomized phase 2B study published in Journal of Clinical Oncology.
The modalities conferred similar rates of PFS and OS among this patient population.
“The physical nature of particle therapy allows the dose deposition [to occur at a] very discrete and defined location within the beam line based on the energy of the beam; normal tissues beyond this point get very little to no radiation,” Steven H. Lin, MD, PhD, physician-scientist and radiation oncologist in the department of radiation oncology at The University of Texas MD Anderson Cancer Center, told Healio. “X-rays, on the other hand, enter the body at a higher energy and exit the body at lower energies, leaving a trail of radiation through the tumor and beyond.
“Although IMRT planning allows for a relatively low dose to scatter beyond the tumor throughout the normal organs, this dose through the heart and lungs for patients with esophageal cancer is sufficient to cause some post-radiation consequences,” Lin added. “The dose-sparing effect of proton beam therapy to the heart and lungs allows those organs to recover better from the stress and trauma of surgery. For patients who do not get surgery, it reduces the extent of late-term side effects of radiation-related injury to these critical organs.”
It remained unclear, however, whether the dosimetric benefits of proton beam therapy (PBT) translate to better clinical outcomes compared with IMRT.
The analysis included 107 patients with locally advanced esophageal cancer (median age, 67 years; range, 33-84; 90.7% women; 91.6% white). Lin and colleagues randomly assigned them to PBT (n = 46) or IMRT (n = 61) at a dose of 50.4 Gy.
Investigators compared toxicity and PFS between groups.
Researchers stratified patients by histology, resectability, induction chemotherapy and stage.
Total toxicity burden — a composite score of 11 distinct adverse events — and PFS served as the study’s co-primary endpoints. Distinct adverse events included common toxicities, as well as postoperative complications within 1 year of treatment.
Researchers conducted the trial using Bayesian group sequential design with interim analyses planned at 33%, 50% and 67% of expected accrual.
Median follow-up was 44.1 months.
Nearly half of patients in each group (IMRT, n = 30; PBT, n = 21) underwent esophagectomy, and 80% of PBT was passive scattering.
Results showed posterior mean total toxicity burden was more than twice as high with IMRT (39.9; 95% highest posterior density interval, 26.2-54.9) compared with PBT (17.4; 10.5-25). Among those who underwent surgery, the mean postoperative complication score was more than seven times higher for IMRT (19.1; 7.3-32.3) vs. PBT (2.5; 0.3-5.2).
Researchers reported a posterior probability of lower mean total toxicity burden for PBT compared with IMRT of 0.9989, which exceeded the study’s stopping boundary of 0.9942 at the 67% interim analysis.
PBT and IMRT conferred similar rates of 3-year PFS (50.8% vs. 51.2%) and 3-year OS (44.5% vs. 44.5%).
The small sample size, as well as total toxicity burden not being a validated endpoint, served as limitations to this study.
“The use of PBT further reduces the dose to normal tissues, even when compared with IMRT,” Lin told Healio. “For patients with esophageal cancers, this additional dose reduction to the heart and lungs can further reduce the toxicities of chemoradiation.
“As therapies improve patients’ OS outcomes, the long-term consequence of therapy becomes very important,” he added. “This long-term consequence is lower for PBT, and therefore, eventually it will become the preferred standard treatment over IMRT.” – by John DeRosier
For more information:
Steven H. Lin, MD, PhD, can be reached at firstname.lastname@example.org.
Lin reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.