Scripps Proton Medical Director Cites Flaws in JAMA Article Findings

Note to Patients: The following news is posted for archival purposes only. Scripps is no longer accepting new patients for proton therapy.

The Journal of the American Medical Association (JAMA) published an article today that compared three patient treatment methods for prostate cancer patients: conformal radiation therapy (CRT), intensity-modulated radiation therapy (IMRT), and proton therapy.

In the JAMA article, researchers at the University of North Carolina reached what Scripps believes are misguided conclusions that proton therapy treatment is no more effective than IMRT in treating prostate cancer — and that proton therapy is more likely to cause adverse bowel issues than IMRT.

Dr. Carl Rossi, medical director of Scripps Proton Therapy Center, believes the methodology of this research is seriously flawed and that the conclusions in the article may create public misperceptions about the safety and effectiveness of proton therapy for prostate cancer patients. Important differences in the treatment and follow-up between proton and IMRT patients were not taken into account in this study.

For example:

In this study, no distinction is made regarding the total radiation dose given to the proton patients vs. the IMRT patients. In general (and particularly during the time period that the study patients were treated) proton beam patients routinely receive higher radiation doses than IMRT patients. This is because randomized proton beam trials have proven the benefit (in terms of a better chance of preventing recurrence of prostate cancer) of higher radiation doses.

One consequence of this higher dose is an increased risk of minor bowel side effects. However, published proton beam data (including data published in JAMA in 2010) shows that, unlike IMRT, the higher radiation dose given to the proton patients did not lead to a higher incidence of severe complications.

No effort was made in the UNC study to evaluate the possible differences in treatment planning and treatment delivery between proton and IMRT patients. Was the same volume of rectum included in the planning volume? How was the high-dose volume defined? These are factors which are typically analyzed when studying radiation side effects and attempting to compare different types of radiotherapy.

Unlike IMRT, the vast majority of the proton beam patients treated during the UNC study period received their treatment at one or two academic centers. Proton patients were being treated on protocols which, by design, subjected them to regular, rigorous follow-up and which mandated referral to a GI specialist at the least sign of any bowel issues. This means that the proton patients were far more likely to be referred for GI evaluation than the IMRT patients. Since the UNC study only evaluated whether or not the patients were ever seen by a GI doctor, not on the severity of their complaints, the “difference” seen between the groups is likely of little if any clinical consequence.

The UNC study stands in direct opposition to the published results of a multi-institutional prospective, randomized trial of proton beam treatment of prostate cancer which showed far less bowel toxicity than that experienced by IMRT patients who received a radiation dose equivalent to that of the proton beam patients.

In conclusion, the UNC study does not prove that IMRT treatment of prostate cancer is superior to proton beam therapy. Rather, as its authors point out, it demonstrates that further investigation of both treatment methods is warranted. Such trials are already under way at several institutions in the United States.