Image-guided IMRT reduces bowel effects in cervical cancer patients
Dr Supriya Chopra - Tata Memorial Centre, Mumbai, India
This is a study that we started way back in 2011 that we did. The main reason for doing that is that most of the time patients who have early cervical cancer and get operated and require further treatment because of some poor risk factors that are identified on pathology. So the risk-benefit ratio, it’s very, very clear if you have high risk features you have to go ahead with post-operative radiation but sometimes if you have intermediate risk factors the risk-benefit ratio is not that clear or it’s not very great so you surely don’t want to give too much toxicity to patients. Even for high risk patients, because they are early cervical cancer and they are going to survival longer than other patients, you want to be sure that the toxicity is less. So once you use post-operative radiation. Now, a substantial proportion of patients would have moderate to severe bowel toxicity and this evolves as their life evolves. Most of the patients would be continually bothered about having chronic diarrhoea or having an abdominal bloating sensation which cannot be cured by anything or just having some lower abdominal pain which definitely affects their quality of life but there’s no way to reduce it.
So in 2011 we started this randomised trial which utilised a new radiation technique called IMRT which reduces dose to the adjacent bowel structures. Once you use it you are able to potentially reduce side effects. The study was looking into are we really able to do it – everything looks good when you plan treatment for the patient, does it affect patient reported outcomes or toxicity when you measure? So we planned to accrue around 240 patients and planned a mid-treatment analysis at 120 patients when these patients reached almost 18 months of follow-up. At that time point we observed that there was almost a 14% difference in their grade 2 and higher toxicity and a 14% difference in grade 3 and higher toxicity with the use of IMRT. IMRT could reduce it by 14% but just going by the statistical part of it. The difference was not identified to be statistically significant so we are hoping to accrue more patients on this study, a completely planned accrual of 240, and then have a final analysis. These early results are very encouraging but not robust enough to change practice at the moment so we still wait. IMRT is still not a standard of care, we’ll have to wait for the final results of the study. I think the benefit that would be drawn out of the study is not restricted to cervical cancer patients because endometrial cancer, which is more common in the UK, Europe and America, they get treated in exactly the same way once they undergo surgery and require post-operative radiation. So the results of the study would be applicable to patients with endometrial cancer, prostate cancer, rectal cancer who require post-operative pelvic radiation. So we wait to accrue more patients and have the final analysis.
What does a 14% reduction really mean for patients?
It’s a major difference for the patients, 14%. We really debated is this a time point to stop this trial and say that IMRT is standard of care but no, statistical endpoints are not met. Clinically it looks very different but there is obviously a chance that when you’re doing interim analysis when the total number of patients is less the chance is that you falsely conclude that something is better when really speaking it is not. I want to also highlight that at present the follow up is short, it’s just 20 months. So toxicity sometimes continues to evolve so you don’t want to be in a situation where later on at three years you observe that the difference is really not there. So I will be cautious.
What is standard practice for radiation therapy of cervical cancer in India?
Standard practice is 3D conformal radiation in which patients would receive 4-field box radiation and that is pretty much standard throughout the world. Patients of cervical cancer, in addition they receive concurrent chemotherapy if they have high risk factors as compared to an endometrial cancer who may not receive concurrent chemotherapy or receive after completing radiation.
How applicable are your results to the rest of the world?
If this trial turns out to be positive, it will be practice changing because right now IMRT is not standard of care in America, the UK, US, India. Any part of the world post-operative IMRT is not standard of care and these results are very, very encouraging for the use of IMRT but statistically they are not robust enough. They will be applicable throughout the globe.
When do you hope to finish recruiting into the study?
We’ve already accrued 167 patients on the study and I think it will be another two years before we complete the study accrual. The median follow up has to be around three years so I’m hoping by the end of 2018 we’ll have some more insights into the results of the study.
Are you aware of any other trials looking at this topic?
Not with the similar endpoint but I’m aware that RTOG is doing a similar study in endometrial and cervical cancer patients but their primary endpoint is week five toxicity; they’re not looking at late toxicity. In addition, I think they’re looking to patient reported outcomes as the primary endpoint whereas that is a secondary endpoint in our study. So it’s a similar design so it would be very interesting. I am aware that they have just accrued their last patient so they may be also out with their results in six months to a year.
What is your take-home message?
The only thing is that we shouldn’t jump the gun and start using IMRT because toxicities are evolving. The clinical difference, being a clinician, it looks to be very, very important, 14% is not a small difference. But then we have to go by the methodology of doing a randomised trial. If the statistics say that it is not significant then it’s not significant.