In Sinonasal Cancer, New Radiotherapy Trumps Old?

Nick Mulcahy

July 10, 2014

In oncology, there is an ongoing question about proton-beam therapy that is made urgent by its costliness: Does it provide better outcomes than older forms of radiotherapy?

There are theoretic reasons that suggest it is better. Now, theory might be catching up with practice, at least in cancer of the nasal cavity and paranasal sinuses.

Researchers from the Mayo Clinic report that "charged-particle therapy," which includes proton-beam therapy, appears to be more effective than traditional photon therapy in these sinonasal cancers.

At 5 years, pooled overall survival was significantly better with charged-particle therapy than with photon therapy in an analysis of more than 1400 patients from 41 noncomparative observational studies (relative risk [RR], 1.51; P = .0038).

Disease-free survival was also significantly better at 5 years with charged-particle therapy than with photon therapy (RR, 1·93; P = .0003).

The meta-analysis was published online June 27 in the Lancet Oncology.

The clinical benefits of charged-particle therapy might reflect theoretic advantages, according Samir Patel, MD, from the Mayo Clinic in Scottsdale, Arizona, and colleagues.

They observe that tumors in the paranasal sinus and nasal cavity are in close proximity to the vital structures of the brain, eyes, cranial nerves, and optic pathways.

Thus, the "unique physical properties" of charged-particle therapy, including the "rapid fall off" of dose beyond its peak, could allow clinicians to escalate dose and improve tumor control and survival, despite these tight quarters.

On the basis of their findings, the investigators state that "the theoretical advantages of charged-particle therapy might in fact be real."

An expert not involved in the study agrees — up to a point.

"I agree that sinus and nasal cancers and protons are an ideal fit theoretically," said Piet Dirix, MD, PhD, from the Iridium Cancer Network in Wilrijk, Belgium.

Particle therapy is clearly the best choice for base-of-skull tumors.

"Particle therapy is clearly the best choice for base-of-skull tumors," he told Medscape Medical News in an email.

But there is a problem. "Evidence is still lacking, despite this good-quality meta-analysis," he noted.

In addition to not containing any trials that were randomized, the meta-analysis is potentially flawed, he explained.

Selection bias, which is "very important," might have occurred in the study. To their credit, the investigators acknowledge as much.

A higher proportion of patients with high-risk histologic types were treated with photon therapy than with charged-particle therapy (50% vs 27%; P = .06), they report, which could have resulted in selection bias.

But there were also higher proportions of patients with recurrent previously treated disease and advanced disease in the charged-particle group, said senior investigator Robert Foote, MD, from the Mayo Clinic in Rochester, Minnesota, in an email.

None of these differences between the 2 groups were statistically significant, he told Medscape Medical News.

Dr. Dirix noted that "the number of proton therapy centers is very limited."

"Most" of the 286 patients who received charged-particle therapy, including proton-beam therapy, were treated at just 3 centers — the Massachusetts General Hospital in Boston; the National Cancer Center Hospital East in Chiba, Japan; and the Hyogo Ion Beam Medical Center in Japan — the investigators report.

In contrast, the 1186 patients who underwent photon therapy were treated at a variety of centers in a number of different countries, including Belgium (in a study led by Dr. Dirix).

Surgery is the "mainstay" of treatment for early-stage resectable sinonasal cancers, the investigators state. But radiation therapy is needed as an adjunct in advanced disease and as primary therapy for unresectable cancers and for patients who are not candidates for surgery.

Charged-particle therapy is heterogenous in terms of the actual particles (carbon ion and proton) and delivery techniques, Dr. Patel and colleagues point out.

Photon therapies in the analysis included, among other techniques, 3D conformal radiotherapy and intensity-modulated radiation therapy (IMRT).

In a subgroup analysis, the investigators compared the 2 leading types from each group — proton-beam therapy and IMRT. Disease-free survival was significantly better with proton-beam therapy than with IMRT at 5 years (RR, 1.44; P = .045), as was locoregional control at the longest follow-up (RR, 1.26; P = .011).

The only measure in the study in which charged-particle therapy did not trump the older photon therapy was in locoregional control, which did not differ between treatment groups at 5 years (RR, 1.06; P = .79).

However, locoregional control was better with charged-particle therapy than with photon therapy at longest follow-up (RR, 1.18; P = .031).

Charged-particle therapy is coming on strong in the United States, where there are multiple proton-beam therapy centers under construction and going online.

However, there has been criticism that proton-beam therapy is being "hyped" and that it "sells hope" without any clear benefit for patients.

The new technology is also far more expensive than other radiotherapy. For instance, a 2013 report noted that the median Medicare reimbursement for prostate cancer treatment was $32,428 for proton therapy and $18,575 for IMRT.

In fact, some private medical insurers have stopped reimbursing proton-beam therapy for prostate cancer because of the lack of evidence of its advantages, as reported by Medscape Medical News.

In addition, there are still unknowns about best usage. "Several problems regarding proton therapy — for example, the lack of image guidance — need to be solved," Dr. Dirix said.

This study was funded by the Mayo Foundation for Medical Education and Research. Dr. Patel, Dr. Foote, and Dr. Dirix have disclosed no relevant financial relationships.

Lancet Oncol. Published online June 27, 2014. Abstract


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