Radiotherapy protocol deviations: an interview with Dr Nitin Ohri

Interview conducted by April Cashin-Garbutt, MA (Editor)Nov 12 2012

Please could you give a brief introduction to radiotherapy?

Radiotherapy is a key component of cancer therapy. A majority of cancer patients get radiotherapy in some form at some point in their disease course. It can be used in a curative setting or in a palliative setting.

What types of radiotherapy did your recent research look at?

My recent research was focusing on radiotherapy trials performed by cooperative cancer study groups. What the trials had in common is that they were all external radiotherapy. This means that they were using X-rays generated by a machine directed at the patient externally, rather than internally implanting a device.

Aside from that, the studies included in my analysis varied widely. Some of them were pediatric patients, some were adult patients. There were a wide variety of disease sites. There were all curative disease therapies though.

Please could you outline current radiotherapy protocols?

The recommended use of radiotherapy varied depending on:

• the diagnosis
• the stage
• the particular patient
• what kinds of other therapy they were receiving

What I did was looked at radiotherapy trials and in each radiotherapy trial there were instructions on how the radiotherapy should be delivered based on what was thought to be appropriate at the time the study was designed. I was looking at what the effects, or associations, are of delivering radiotherapy that does not meet those pre-specified criteria.

Your recent research looked at the effects of deviations from these protocols. What kinds of deviation did you look at?

What I did was an analysis based on published reports by other investigators. In each case they assigned deviation differently depending on these sites. For example, for a trial of treating pediatric patients with brain tumors, they would define deviation as being a treatment area that did not include the whole brain, or had an inadequate safety margin around the brain, or if the calculated dose was not appropriate.

In other cases, for example in head and neck cancer, it may be that deviation was assigned if a certain high risk lymph node region was left out of treatment. It really varied significantly depending on the disease site.

What were the effects of these deviations?

I found that there were eight papers that met the criteria of exploring the association of these deviations with outcomes for patients. In 6 of those 8 studies, overall survival data were provided and in 6 out of 8, other end points were reported like local control, or disease-free survival. In all of these studies except for one, radiation deviations were associated with worse clinical outcomes, including overall survival.

What I did was called a meta-analysis, which is a statistical technique to combine the effects from different studies to try to summarize the data in a quantitative way. The summary statistics indicated that based on the available data deviations some radiation protocols are associated with an approximately 75% increase in the risk of treatment failure and death.

What impact do you think your work will have?

Cooperative groups have understood for some time, and it intuitively makes sense, that if you don’t deliver the radiotherapy appropriately the outcomes may suffer. Over the past decade some cooperative groups have been incorporating quality assurance measures into their trials. What has not been well established is how important are these deviations – that is where my analysis helps in quantifying the consequences of not delivering appropriate radiotherapy.

What we still don’t know is what measures should be put in place. One strategy is that the study coordinators look over every radiation plan before the patient actually starts to get treated. In some ways that would be ideal as you can tell the people treating the patient to make changes and have those changes reviewed, that way no therapy will start before it is checked over. But, the downside of that is that it is very labor intensive and is also very time consuming. In lots of cases, it is important to start radiotherapy in a timely fashion. Having these sorts of complicated real-time procedures may cause significant treatment delays.

It is really a challenge for physicians these days to come up with quality assurance that reviews the techniques that are both effective and also efficient. That is a big challenge for cooperative groups. Currently, the lead radiation cooperation group in the US is the radiation therapy oncology group (RTOG) and they have different policies in place, each on a trial by trial basis. Some trials are reviewed real-time, some trials’ radiation plans are reviewed semi-annually or quarterly and if deviations are noted then changes can be made to the protocol, but it may be too late to make changes to the treatment of the patients that have been treated already.

Do you have any plans for further research into this topic?

Yes, absolutely. I am working at my own institution which is Albert Einstein Medical College, in the Bronx, to strengthen and develop our own quality assurance procedures. In our department I am also hoping to continue to work with the cooperative groups to try and analyze data they’ve already collected to come up with hypothesizes about how quality assurance procedures should be carried out in the future.

Would you like to make any further comments?

One interesting implication of the work that I did was that I only was looking at radiation protocols, which were patients treated during clinical studies, but the vast majority of patients receive treatment as part of routine clinical care, which means they are treated with standard treatment techniques that is outside of studies.

If patients that are being treated at academic centers, presumably by experts in their field, are having such deviations from what are recommended, one can only imagine what is happening to patients that are treated off of these studies, without these centralized reviews. So once we work out what the best quality assurance procedures are, they may benefit even more patients who are treated outside clinical trials, which account for about 97% of patients in the US.

Where can readers find more information?

They can find more information on the ASTRO website: https://www.astro.org/

About Dr Nitin Ohri

Dr. Nitin Ohri is a graduate of the Washington University School of Medicine.  He performed residency training in Radiation Oncology at Thomas Jefferson University. 

He is currently an assistant professor at Albert Einstein College of Medicine and a radiation oncologist at Montefiore Einstein Center for Cancer Care in New York City.

Dr. Ohri specializes in the management of lung, liver and soft tissue malignancies.  His research interests include the use of functional imaging for radiotherapy planning and response assessment, development of models to predict clinical outcomes following radiotherapy, and the combination of radiotherapy with immunomodulatory agents.