We applaud the careful wording in this release and all the caveats provided. At the same time, because cancer effects such an emotional response in audiences, including journalists, there is an even higher standard one must meet to provide the appropriate notes of caution. One way to have done this here would have been to flag in the lead sentence — if not the headline — that this is a very small study showing a survival benefit that is less than a year. And at what cost? We don’t know. And with what type of quality of life? We don’t know that either.
Lung cancer is strongly associated with cigarette smoking and remains the most common cause of death due to cancer in the United States. This study reports 5-year treatment outcomes of stage 3 non-small cell lung cancer at a single cancer center. Stage 3 generally means that it is not localized and amenable to surgery, but falls short of widely metastatic (stage 4). All patients in this study (n=64) were treated with chemotherapy and a specific form of radiation therapy (proton beam). There was no concurrent comparison group and results were compared to historical trends.
The release reports that this therapy “prolonged survival” over up to 5 years of follow-up. Compared to historical trends the 29 percent 5-year overall survival (and 26.5 month median overall survival) is quite good. As the lead author comments in the release, the main limitation of the study is how these outcomes compare to current therapy since the study was begun in 2006. Major changes in therapy have taken place. The release comments on new forms of radiation therapy, intensity-modulated radiation therapy, but doesn’t mention new targeted therapies for lung cancer that depend upon genetic analyses. Thus, without a concurrent control group, the reader can’t really be sure how these results would compare to other treatments in similar institutions. Even if these outcomes are superior to what was available at that time, it doesn’t necessarily mean that proton beam therapy will offer the same benefit when added to currently available therapies.
We’re not talking about a few pills a day here. We are talking about ongoing expensive treatment for five years. The costs needed to be explained as well as whether those costs are typically covered by insurance, especially in the kind of political climate we are in now, where health care coverage is the subject of hot debate. It is important for studies such as this to begin addressing the cost of care.
The release spells out the different measurements in both relative and absolute terms about the benefits of the therapy, but it is full of so much medical jargon that journalists and others would have a hard time following. The clearest statement is that they found “an overall survival (OS) of 26.5 months. In contrast, the historical OS rate with standard of care concurrent chemotherapy and traditional radiation was 16 months at the time when the study was designed.” Contrast that with, “In sum, 39 patients experienced a relapse, with distant sites representing 62 percent of all recurrences.” What is a distant site? Were these people living on islands? What they mean is that in 62 percent of the cases where cancer came back, it was where the cancer had spread to other parts of the body. But it’s unclear what this means in relation to the overall purpose of the study. The primary outcome reported is overall survival: 29 percent were alive at 5 years, meaning 71 percent had died. As discussed elsewhere, the key issue is, compared to what?
The release says:
“Among the acute and late toxic effects diagnosed in patients were: esophagitis, pneumonitis and cardiac arrhythmia. Of note, said Chang, no patients developed the most severe, or grade five, toxicities, as seen in patients who receive standard of care.”
So we give the release credit for talking about harms. Some numbers to show how many of the 64 people enrolled had side effects would have been helpful.
We like how the release provided good explanations of the study’s limitations. The release says, for example:
“Chang noted his study is not without limitations. Of greatest significance: the study was designed more than a decade ago. While the study’s survival, recurrence rates and toxic effects are still favorable when compared to rates associated with the most advanced traditional photon radiation therapy, intensity modulated radiation therapy (IMRT), technology to diagnose and stage the disease, as well all treatment modalities have significantly improved.”
At the same time, this is also a lead-in for MD Anderson to advertise therapies that have little evidence behind them. The release goes on to say,
“For example, MD Anderson proton therapy patients with advanced lung cancer now can receive IMPT. The technique uses an intricate network of magnets to aim a narrow proton beam at a tumor and “paint” the radiation dose onto it layer by layer. Healthy tissue surrounding the tumor is spared, and side effects are even more reduced than earlier proton delivery, said Chang.”
OK, but that was not part of the study. So, in effect, the release is saying that there was a marginal benefit shown in a very small study but, hey, come try this new therapy instead!
This is also key info:
“The study opened at MD Anderson in 2006; in this research, Chang and his colleague report on the study’s five-year results. For the prospective Phase II trial, 64 patients with inoperable, Stage III non-small-cell lung cancer were enrolled. The study’s primary endpoint was OS.”
It explains that this was a single site study, in a small number of individuals with a particular type and stage of lung cancer, with overall survival as the primary outcome. But it could have been more clear that there was no direct comparison group and the study was not experimental (randomized design).
There is no disease mongering in the release. Despite the favorable reporting of outcomes, most patients were dead at 5 years.
There is no mention of funding or conflicts of interest in this release.
The release states that results were compared to historical controls, but then goes on to detail all of the limitations with this comparison. The release does mention intensity-modulated radiation therapy (IMRT) at the end and states the historical control was chemotherapy with conventional radiation.
The alternatives could have been presented in a more straight-forward way.
How widespread the treatment options are is not clear. The release does clearly state that this was done at a single site. However, it would have been relatively easy to state that there are only a small number of facilities that can deliver proton beam therapy.
The novelty of the findings are summarized in this sentence: “The findings are the final results of the single institution, Phase II study and represent the longest follow-up to date of stage 3 lung cancer patients who have received proton therapy.”
The release focuses on long-term efficacy and safety. This is what is supposedly novel. The treatment itself isn’t. Again, this could have been made clearer, but it can be discerned on a careful read.
There is no unjustifiable language in the release. However, the headline could have been improved. It states, “Concurrent chemotherapy, proton therapy improves survival in patients with advanced lung cancer.” The first line of the release then clarifies this, “For patients with advanced, inoperable stage 3 lung cancer, concurrent chemotherapy and the specialized radiation treatment, proton therapy, offers improved survival compared to historical data for standard of care.”