Cancer Network: What were some other important or interesting findings from the study?
Dr. Huddart: The other thing that we wanted to show was that the hypofractionated regimen of 36 Gy and six fractions, across both arms, actually achieves a good level of local control. We expected that the local control rate would be about 60% and wanted to rule out a rate lower than 40%.
Of the patients we were able to assess (47/65 patients), we had a local control rate of over 80%. Assessing this is a little bit tricky, because not every patient can have the ideal assessment modality, but that’s our best estimate. Even if you take all the patients that weren’t able to be assessed and assume they all failed, we get a local control rate of 58%—that’s still a pretty satisfactorily level of control.
We also looked at survival data. It’s quite difficult to know what you would expect from this elderly population, but we had over 80% of patients alive at 6 months post-treatment and a median overall survival of 18 months. At 2 years, over one-third of patients were still alive. Given that that these patients had muscle-invasive bladder cancer and are elderly, I think these are actually very promising results.
I think the data we have from this study—and from a previous pilot study from Royal Marsden that included 50 patients and showed very similar results—suggest that if you’ve got a patient in front of you who looks like they would be eligible for curative treatment, but for whatever reason (social, medical) are not fit enough to come every day for treatment, this regimen of 36 Gy over six weekly fractions is a reasonable treatment approach. The regimen was well tolerated, with some acute toxicity. The control rates were not that dissimilar from what you’d expect from a standard course of radiotherapy, and the survival is respectable. I think some form of image guidance will improve the quality of treatment. It then depends on your healthcare system whether you want to do the more adaptive approach, which needs more investment in terms of money and resources.
Cancer Network: Could you discuss the extra time involved in the adaptive treatment planning? How is it more resource intensive, and does it require more time from patients as well?
Dr. Huddart: In this study, we based our plans on a single CT scan, so the CT scan that the patient attends for planning is exactly the same as if they were receiving standard of care. Because the bladder is fairly round, a pretty straightforward conformal plan was used. The physics department and dosimetrist, however, are making three plans rather than a single plan. The dosimetrists who do the work with me say it probably takes twice as long—not three times as long—as they’re using the same type of beam arrangements and just making the Gy volumes different. So it does double that planning input.
In terms of the time for the patient, most of our work suggests you can select the plan in about 5 minutes. Most patients completed treatment in about 12–15 minutes. Given older patients take a bit of extra setting up, this is pretty reasonable and achievable in most radiation departments.
Cancer Network: Are there plans to continue following these patients or study this approach in other patient populations?
Dr. Huddart: The data we have here on adaptive planning is promising in terms of supporting that this approach may offer benefit for patients. A formal comparative study is needed, though, and I think this data should encourage us to carry on this approach in the future, in either this context or other contexts.
One of the reasons we want to prove that adaptive planning actually makes things better is because that time investment is required, but that will require further study. We have been back to the funders to ask whether they would support a larger continuation study, but unfortunately we have been unsuccessful so far. It’s disappointing that we’ve not yet been able to support that larger confirmatory study, but some of this data has only recently come through so there may still be a chance.