Proton therapy stakeholder refutes JAMA study

In the wake of a study published April 17 in the Journal of the American Medical Association (JAMA) which reported an increased incidence of gastrointestinal morbidity among men with prostate cancer treated with proton therapy compared with intensity-modulated radiation therapy (IMRT), proton therapy providers have rallied to dispute the findings and study methodology.

An analysis of the Surveillance, Epidemiology, and End Results (SEER) database may not be the right approach and methodology to make statements about treatment modalities, Eugen B. Hug, MD, chief medical officer of ProCure Treatment Centers, told Health Imaging in an interview.

“This study insinuates that it is a comparison of treatment modalities [IMRT, conformal radiation therapy and proton therapy], but it really is not."

The JAMA study was a retrospective analysis of SEER data. One of the fundamental flaws associated with relying on these data; however, is that information about radiation dose is lacking. Patients treated with proton therapy during the study period from 2005 to 2009 may have received higher radiation doses than currently given as providers attempted to define dose limits. If this were the case, it might explain the inflated incidence of gastrointestinal morbidities.

Although this type of study provides some hints about the tendencies of treatment modalities, it does not provide a basis to form conclusions about those modalities, said Hug, who suggested a more useful approach would have been to supplement the analysis with variables such as radiation dose, including total radiation dose delivered, the dose given and the volume of normal structures receiving low, intermediate and high doses.

A second issue with the study is the incongruence between its results and clinical experience and previously published studies. “People on the ground treating patients with proton therapy have not seen these high rates of gastrointestinal morbidities,” said Hug.

In the JAMA study, researchers reported an absolute risk of gastrointestinal morbidity of 17.8 per 100 person-years with proton therapy vs. 12.2 with IMRT. However, previously published studies of proton therapy contradict the current study. One study published March 17, 2010, in JAMA reported gastrointestinal severe side effects of 2 percent and genitourinary severe side effects at 1 percent.

Hug agreed with the study authors on a few points and emphasized the need for appropriate clinical studies to evaluate the effectiveness and limitations of treatment options. He concluded, “The bottom line is as the authors suggest: More clinical studies are needed.”