Proton Therapy Not Better Than IMRT in Lung Cancer

Roxanne Nelson, RN, BSN

January 18, 2018

The first randomized trial to compare proton therapy with conventional radiotherapy has not found a difference in toxicity, which is the main claim for superiority of proton therapy.

The trial was conducted in patients with inoperable non-small cell lung cancer (NSCLC) and showed that proton therapy was not superior in reducing serious lung toxicity compared with intensity-modulated (photon) radiotherapy (IMRT).

This finding "challenges the assumption on the part of many that protons would certainly be superior and emphasizes the importance of evidence-based medicine and randomized trials," comments Feng-Ming (Spring) Kong, MD, from the Indiana University School of Medicine, Indianapolis, in an editorial that accompanies the publication of the findings.

"Personally, as a radiation oncologist, I would not recommend proton therapy for NSCLC outside a clinical trial setting until a clinical benefit is demonstrated in a prospective randomized study," she writes.

The  results were published online January 2 in the Journal of Clinical Oncology.

They were initially presented at the 2016 annual meeting of the American Society of Clinical Oncology and reported at the time by Medscape Medical News.  Discussing the new results at the meeting, Martin Edelman, MD, from the University of Maryland Greenebaum Cancer Center in Baltimore, said that proton therapy should remain experimental in this setting.

"Radiation oncologists have the same obligation as medical oncologists," Dr Edelman pointed out. "A technology, like a drug, should not be adopted until its benefits are demonstrated."

Similar Results for Both Therapies

The randomized trial, conducted by Zhongxing Liao, MD, from the University of Texas MD Anderson Cancer Center in Houston, and colleagues, involved 149 patients with inoperable NSCLC. The cohort was randomly assigned to receive one of the two  radiation therapies if both plans met the same prespecified dose-volume constraints for at-risk organs at the same tumor dose (n = 92 for IMRT and n = 57 for proton therapy).

The trial set out to determine whether proton therapy would reduce lung toxicity compared with IMRT. The end point was grade 3 or greater radiation pneumonitis (RP).

It did not.

The proton therapy group had a 10.5% rate of grade 3 or greater RP at 1 year compared with only 6.5% in the IMRT group (P = .537), despite a significant reduction in low-dose volume in the dosimetric histograms for the proton therapy group, as the editorialist points out.

However, two patients receiving IMRT had grade 5 RP vs none with grade 4 or 5 RP in the proton therapy group, the authors point out.  In addition, while the outcome improved in both groups, "the magnitude of improvement in RP was greater and statistically more significant in the PSPT [proton therapy] arm," they comment.

The other endpoint of the trial was local failure, which also did not significantly differ between the two treatment groups: The local failure rate at 1 year was 10.9% after IMRT and 10.5% after proton therapy (P = 1.0).

Compared with conventional radiotherapy,  proton therapy exposed less lung tissue at doses of 5 to 10 Gy (relative biologic effectiveness), but more lung tissue was exposed at doses greater than 20 Gy (relative biologic effectiveness).

The mean radiation dose to the heart was significantly reduced with proton therapy (P = .002), but  mean doses to the lung or esophagus did not differ between the two modalities.

The median overall survival was similar for the two groups: 29.5 months for the IMRT group vs 26.1 months for the proton therapy group (P = .297).

The authors conclude that they found no benefit in grade 3 or greater RP or local failure after proton therapy, presumably because proton therapy was not associated with improved lung dose-volume indices.

Looking Ahead  

The results of the current study suggest a "dismal future" for proton therapy in locally advanced NSCLC, Dr Kong writes in the editorial, but  these negative results "cannot exclude the potential benefit of proton therapy in other clinical situations, such as for pediatric patients."

There may be room for optimism, she adds.

Uptake of proton therapy has been slow mainly because of cost (a proton therapy center costs about 40 times more than an IMRT center, she points out), but this will fall in the future. "The cost of proton therapy will be significantly reduced by newer technological changes," Dr Kong predicts..

"With decreased costs, improved delivery systems, decreased doses to normal tissues including immune system, and improved understanding of the biology, proton therapy may yet be proven to be a cost-effective cancer treatment of specific diseases in specific settings," she concludes.

 The study was supported by the National Cancer Institute. Dr Liao has disclosed relationships with Varian Medical Systems; several coauthors have disclosed relationships with industry.  Dr Kong has disclosed relationships with Varian Medical Systems.

J Clin Oncol. Published online on January 2, 2018. Abstract, Editorial

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