CHICAGO (FRONTLINE MEDICAL NEWS) – Whether proton radiotherapy is an option superior to photon radiotherapy for patients with non–small-cell lung cancer is still unclear, in light of results from a small randomized clinical trial and a review of the National Cancer Data Base.

The randomized trial of 149 patients showed there was no significant difference in radiation pneumonitis incidence rate nor overall survival by treatment received, while a retrospective analysis of 140,383 patients revealed that receipt of proton radiotherapy was associated with higher 5-year survival rates. The findings were presented at the annual meeting of the American Society of Clinical Oncology.

The Bayesian randomized trial compared rates of treatment failure and adverse events in patients receiving either intensity-modulated radiotherapy (IMRT) or 3D passively scattered proton therapy (3DPT). Of the 149 patients who met randomization requirements, 92 received IMRT and 57 received 3DPT. All patients received concurrent chemotherapy, and the patient characteristics were well balanced, although in the 3DPT group target volumes were larger.

Treatment failure rates at 12 months were 15.6% in the IMRT group and 24.6% in the 3DPT group. The median time to treatment failure was 10.5 months for both groups, reported Dr. Zhongxing Liao of the University of Texas MD Anderson Cancer Center, Houston.

The incident rates of radiation pneumonitis were 7.2% among patients receiving IMRT and 11% among patients receiving 3DPT; the median time to radiation pneumonitis was 4.5 and 4.0 months, respectively.

Dr. Liao pointed out that, historically, incidence rates of radiation pneumonitis were 15% in IMRT and 5% in 3DPT, and that rates observed in this study represented a deviation from those rates.

Local recurrence occurred in 22.8% of the IMRT patients and 24.6% of the 3DPT patients; time to local occurrence was 12.7 and 13.4 months, respectively. Finally, statistical analysis revealed no significant difference in overall survival by treatment received, Dr. Liao reported.

“Considerably fewer [adverse] events occurred in the current trial actually suggesting that both IMRT and the proton [therapy] are excellent treatments for non–small-cell lung cancer,” Dr. Liao said. “No differences were found between IMRT versus 3DPT in treatment failure in this randomized trial.”

Dr. Liao pointed out that as the trial went on, patients experienced fewer adverse events and went longer periods of time before experiencing treatment failure. This was an indication that the administration of both proton therapy and radiation therapy improved over time, he said.

In another study presented at the meeting, investigators used the National Cancer Data Base to collect demographic and clinical data on 140,383 patients with non–small-cell lung cancer who were treated with thoracic radiation from 2004 to 2012.

Across the entire cohort, median age was 68 years, 57% were male, 59% had stage II or III cancer, and 85% of patients were white. Only 348 patients received proton radiotherapy while the remaining 140,035 patients received photon radiotherapy, reported Madhusmita Behera, Ph.D., of Winship Cancer Institute at Emory University in Acworth, Georgia.

Multivariate analysis revealed that receipt of photon radiotherapy was associated with an increased risk of mortality, compared to proton radiotherapy (hazard ratio, 1.46; P less than .001).

For patients with stage II or III disease, 5-year overall survival rates were 15% for those who received photon radiotherapy and 22.3% for those who received proton radiotherapy (P = .01).

Patients were less likely to receive proton radiotherapy in community (odds ratio, .2; P less than .001) or comprehensive community (OR, .32; P less than .001) centers compared to academic centers, Dr. Behera reported.

Among the patients who received proton radiotherapy, 45.12% reported residing in a geographical location (defined by ZIP codes) with a median income quartile of $46,000 or more, the “highest median income quartile according to the U.S. census.” In addition, “only 14% of patients were from ZIP codes where more than 29% did not have a high school degree,” Dr. Behera said.

Both Dr. Behera and Dr. Liao noted that insurance denial continues to be a barrier to proton therapy. Following enrollment, 26 patients were denied insurance coverage for proton radiotherapy, Dr. Liao reported.

“This is only the beginning of the story of randomized trials [studying] proton and photon therapy in lung cancer in my opinion,” Dr. Liao said. “We only randomized patients with equivalent plans which may have excluded patients who could have benefited from protons the most.”

The study headed by Dr. Liao was funded by the MD Anderson Cancer Center and the National Cancer Institute. Dr. Liao had no relevant disclosures. One coinvestigator reported having stock or other ownership interest in Liquid Biotech, USA. The study headed by Dr. Behera was funded by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and the National Cancer Institute. Dr. Behera had no relevant disclosures; four of her coinvestigators disclosed having consulting or advisory roles or receiving financial compensation or honoraria from multiple companies.

On Twitter @jessnicolecraig