Proton therapy may prolong OS in stage II, III NSCLC

Issue: July 25, 2016

CHICAGO — Proton beam therapy improved OS compared with conventional photon-based therapy in patients with stage II/III non–small cell lung cancer, according to results of a retrospective database analysis presented at the ASCO Annual Meeting.

Perspective from Nathan Pennell, MD, PhD

Further, patients with higher income and education levels and those with government-issued insurance treated at academic centers were the most likely to undergo proton therapy.

“Clinical outcomes in patients with newly diagnosed NSCLC are best in patients with resectable early-stage disease where 5-year OS rates range between 15% and 17%,” Madhusmita Behera, PhD, director or Winship Research Informatics at Winship Cancer Institute at Emory University, said during a presentation. “Photon-based external beam radiation plus concurrent chemotherapy is the current standard of care for patients with unresectable stage III NSCLC.”

Proton beam therapy has emerged as an alternative to conventional photon therapy for many cancer types. Recent data suggest proton therapy has a significant advantage in sparing healthy tissue compared with photon therapy. However, it is not known whether proton therapy improves OS in patients with NSCLC.

Behera and colleagues pooled data from the National Cancer Data Base to assess outcomes and predictors associated with thoracic radiation in 140,383 patients (median age, 68 years; 57% men; 59% white) with stage I to stage IV NSCLC treated between 2001 and 2012. Fifty-nine percent of patients had stage II/III disease.

Of these patients, 140,035 were treated with photon therapy and 348 received proton therapy. Seventy-two percent of patients were treated at metropolitan centers and the other 28% were treated at academic centers.

Researchers conducted logistic regression analyses to determine predictors of proton therapy use.

Results showed proton therapy was less likely among patients treated in community (OR = 0.2; P < 0.001) or comprehensive community centers (OR = 0.32; P < 0.001) compared with academic centers.

Further, patients who underwent proton therapy were more likely to have a higher income and education level. Forty-five percent of patients who received proton therapy were from zip codes with a median income of more than $46,000 — the highest income quartile according to the U.S. Census Bureau.

Results of multivariate analysis indicated that the risk for death was greater with use of photon therapy (HR = 1.46; P < .001).

Among patients with stage II/III disease, a greater proportion of those who received proton therapy achieved 5-year OS (22.3% vs. 15%; P = .01). Patients with stage II/III disease who received photon therapy had worse OS in multivariate (HR = 1.19; P = .06) and univariate (HR = 1.23; P = .02) analyses.

Further, results of a propensity-matched analysis showed more patients achieved 5-year OS with proton therapy vs. photon therapy (23% vs. 14%; P = .02).

Median OS was 11 months with photon therapy vs. 19 months with proton therapy.

The researchers acknowledged limitations of their study, including a potential influence of patient section, small sample size and a lack of toxicity data.

“Our results show that thoracic radiation with proton therapy is associated with favorable survival,” Behera said. “Also, the use of proton therapy was associated with higher education and higher income levels as well as treatment received at an academic center. The ongoing phase 3 randomized trial, NRG Oncology 1308, will hopefully provide us with additional information on the role of proton therapy in stage II/III patients.” – by Jennifer Southall

Reference :

Behera M, et al. Abstract 8501. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclosure: Behera reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.

Perspective

Nathan Pennell, MD, PhD

At the ASCO Annual Meeting, two highly anticipated abstracts were presented in the locally advanced non–small cell lung cancer session, both addressing the pressing question of whether proton beam radiation has advantages over conventional, photon-based radiation. Protons theoretically have advantages over photons due to the physical properties of the particles, with protons depositing all of their energy at a specified depth (eg, the Bragg peak) and having no exit dose, thus sparing adjacent tissues. Retrospective and single-institution series have shown that protons can be an effective treatment for patients with NSCLC, but up to this point no direct comparisons with conventional radiation had been completed.
In a retrospective analysis using the National Cancer Data Base (NCDB), Behera and colleagues examined the survival of patients with NSCLC of all stages who were treated with conventional or proton beam radiation. The analysis included 140,383 patients with NSCLC treated with radiation, the vast majority (n = 140,035) of whom were treated with conventional radiation. Only 348 were treated with protons. The researchers did their best to compensate for this huge disparity by using propensity matching and concluded that OS was superior in patients treated with protons compared with photon-based therapy — both in the overall group and in a subset of patients with stage II or III NSCLC, in which 78,000 patients in the conventional group were compared with only 193 in the proton group.
So does this mean that protons are more effective than photons for treating NSCLC? Unfortunately, this study cannot answer that question adequately. The NCDB is a powerful tool for retrospective analyses, with outcomes data available from 70% of patients treated in the United States, but its power is derived from the sheer numbers of patients available for analysis. It is much less useful when numbers are small. In this study, the conventional arm likely does reflect the real-world outcomes of patients with NSCLC treated with radiation, with a median survival for stage II/III patients of only 13.4 months. Compare that to the median OS of 28.7 months in the recent phase 3 RTOG 0617 trial, and you can easily see the “apples and oranges” difference between a selected trial population and the real-world experience reflected in the NCDB.
In the current study, the proton beam-treated group has a similar problem. The researchers showed that patients treated with protons were more likely to be white, better educated, have a higher socioeconomic status and to be treated at academic centers. Essentially, this study compared those patients — treated in one of only 23 proton centers in the United States — with the rest of the country, and as such, the conclusions really are not interpretable. Given the relatively small numbers and favorable prognostic characteristics of proton-treated patients with NSCLC, this simply is not a question that can be answered retrospectively.
The good news is that there are prospective, randomized trials that should provide better answers to this question. The first was presented by Zhongxing Liao, MD, in the same ASCO session. The randomized phase 2 trial of chemoradiation with protons vs. intensity-modulated radiation therapy for patients with stage III NSCLC demonstrated no significant differences between the two modalities in terms of local control, survival or toxicity.
The second is the ongoing phase 3 RTOG 1308 trial making this same comparison, which should be strongly supported if we hope to ever put this issue to rest.

References:

Bradley JD, et al. Lancet Oncol. 2015;doi;10.1016/S1470-2045(14)71207-0.
Liao Z, et al. Abstract 8500.

Nathan Pennell, MD, PhD

Cleveland Clinic

Disclosures: Pennell reports no relevant financial disclosures.