Hypofractionated Radiation Therapy

Jamie DePolo: Hello. Thanks for listening. Dr. Chirag Shah is a radiation oncologist and director of breast radiation and clinical research in the department of radiation oncology at the Cleveland Clinic. Dr. Shah serves as a reviewer for various medical journals and is a member of various medical societies. His primary research interests are breast cancer, sarcoma, and innovative radiation treatment schedules, as well as lymphedema. He has participated in numerous clinical trials.

Today, he joins us to talk about hypofractionated, or accelerated, radiation schedules; what they are; how they’ve become the standard of care; and why they may be even more important during this time of COVID-19. Dr. Shah, welcome to the podcast.

Dr. Chirag Shah: Thank you for having me.

Jamie DePolo: So, first of all, could you explain the difference between what is called hypofractionated, or accelerated, radiation schedules and the older, a bit more longer radiation schedules, and also if you could tell us how and why these shorter schedules were created.

Dr. Chirag Shah: Of course. So, when we first started doing breast-conserving therapy more than 2 decades ago, we predominantly used what’s called standard fractionation. Standard fractionation is typically when we give radiation in 1.8 to 2 units of radiation a day to a total of 45 to 50 units of radiation. Hypofractionation is an evolving area. The most well-studied techniques use, instead of 25 treatments or so, use 15 to 16 treatments and increase the dose per treatment to 2.67 units. The “hypofractionation” is a technical word to basically say higher doses of radiation therapy.

These techniques were born out of clinical trials outside of the United States that looked to shorten the duration of radiation therapy in both the United Kingdom as well as Canada. And more recently, hypofractionation has gone one step further to look at the delivery of radiation therapy in 5 treatments.

Jamie DePolo: So basically, a person would be getting the same amount of radiation, it’s just you’re getting more radiation at each treatment so the total time is shorter.

Dr. Chirag Shah: Correct. Biologically, we’re giving roughly the same amount of radiation. The total doses in hypofractionation tend to be lower than standard, but because we’re giving higher doses per treatment in quicker time, it’s biologically equivalent.

Jamie DePolo: Okay. And part of the reason, at least my understanding, that these were created were because the traditional schedules, which were 5 to 7 weeks going into a treatment center every day, that could be tough for some people especially if they lived quite a distance from the treatment center.

Dr. Chirag Shah: That’s absolutely correct. So, we have data showing that anywhere from 20 to 40% of patients did not get or complete their radiation due to the long courses of radiation, and for those that lived some distances away from centers it was very burdensome. So hypofractionation definitely was driven by that as well.

Jamie DePolo: Okay. Now, are there any other benefits to this shorter schedule besides making it easier for someone to plan?

Dr. Chirag Shah: Interestingly, there has been some data that suggests that hypofractionation may have slightly better control, but that hasn’t been born out in randomized trials. Additionally, some data has suggested less side effects, but the majority of data has shown equivalent side effect profiles to standard treatment.

Jamie DePolo: Okay. So it’s really a convenience thing. That would be the largest benefit?

Dr. Chirag Shah: Yeah. I’d say that absolutely the largest benefit is a decrease in the amount of time patients have to come in.

Jamie DePolo: Okay. Now, are there any risks? Are there any concerns with somebody having a hypofractionated schedule?

Dr. Chirag Shah: I would say in 2020 using modern dose constraints, we really are quite comfortable, and there’s no potentially additional risks, per se, with standard hypofractionation in 2020.

Jamie DePolo: Okay. I know that the American Society of Clinical Oncology and the National Comprehensive Cancer Network both say that a hypofractionated schedule should be the standard of care for breast cancer for someone who’s getting radiation to treat breast cancer. Is your sense that this is happening everywhere? Are most people being prescribed a hypofractionated schedule, or are some folks still better candidates for a longer schedule? I guess that’s a long way of asking would there be any reason why someone wouldn’t get the shorter schedule?

Dr. Chirag Shah: So, there are still some patients even for our current guidelines where we consider standard treatment. So for example, patients who have active connective tissue disorders like lupus may require standard treatment over hypofractionation. Additionally, the use of hypofractionation and patients who need lymph node radiation is still understudied, so not all of those patients are candidates for hypofractionation.

However, among those patients that are candidates for hypofractionation, published data does suggest that there are still a large number that aren’t being given hypofractionation. So there is some room for improvement there based on current recommendation.

Jamie DePolo: Okay. And do we know why patients who may be good candidates are not getting a hypofractionated schedule?

Dr. Chirag Shah: You know, that’s a great question. Unfortunately, the data hasn’t really shown us the reason why they’re not getting hypofractionation, but there certainly has been a big push in our specialty to really adopt hypofractionation for appropriate patients.

Jamie DePolo: Okay. Because it doesn’t require any different equipment or anything like that, does it?

Dr. Chirag Shah: No. The hypofractionation will be given with standard radiation therapy equipment.

Jamie DePolo: Okay. And if I could back up just a little bit, you mentioned that people with connective tissue disease may not be good candidates for a hypofractionated schedule. Could you explain a little bit why?

Dr. Chirag Shah: Sure. So patients who have connective tissue disorders like lupus with skin manifestation may be at higher risk of skin side effects, and so there is not a lot of data on using hypofractionation in this population. And so we tend to be conservative if we don’t have a large amount of data. That being said, in my own practice, I do discuss the pros and cons of both standard and hypofractionation with these patients.

Jamie DePolo: Okay. So the idea is they may get more severe skin side effects if they have a connective tissue disorder?

Dr. Chirag Shah: That’s correct. Yeah.

Jamie DePolo: Okay. Okay. Now, I’m curious, with the pandemic and people being told, “Don’t go in for treatment unless you absolutely have to,” some treatments being delayed... Have you seen that leading to more doctors preferring a hypofractionated schedule?

Dr. Chirag Shah: Yeah. I would say, you know, first of all, we always counsel patients on the pros and cons of radiation even before the pandemic, and now with the pandemic we have that focus. We also let patients know about the safety precautions at radiation centers to ensure their health and well being.

In terms of hypofractionation, I would say that during the pandemic we’ve seen some large trials published, also, that allow for even further hypofractionation. So I previously mentioned 15 or 16 treatments, but now we’ve had some really seminal studies published looking at 5 treatments. So during a pandemic, I have discussed the use of 5-treatment, both whole breast and partial breast, radiation with patients.

Jamie DePolo: Oh, wow. So that would be significantly shorter. That’s just basically a week.

Dr. Chirag Shah: So the regimens depend on the technique. So for partial breast it’s 5 treatments given in one week. For the whole breast it can be 5 treatments given once a week, which has 10 years’ worth of follow-up, or in some cases 5 treatments of whole breast given in one week, which has only 5 years of follow-up.

Jamie DePolo: Oh, I see. Okay. And overall, you talk about the follow-up, what the researchers are looking at with the follow-up is of course recurrence, you know, does the breast cancer come back? But they’re also looking at sort of the cosmetic outcomes and the side effects, too, correct?

Dr. Chirag Shah: That’s absolutely correct. One of the big concerns with hypofractionation initially was the potential for side effects both in the short and long term and impaired cosmetic outcomes. And what we’ve seen at 10 years with multiple of these regimens is that there was no difference in chronic toxicities and just as importantly no difference in cosmetic outcomes. So that’s why we want to follow patients long term, is to look at cancer outcomes as well as side effect profile.

Jamie DePolo: Okay. So it sounds like if someone’s a good candidate for a hypofractionated schedule, the cosmetic outcome, the side effects, and the long-term recurrence rates are really the same for the more traditional schedule versus the shorter schedule.

Dr. Chirag Shah: Correct. I mean, hypofractionation for appropriate patients really kind of ticks all the boxes currently.

Jamie DePolo: Okay. Now, if someone’s radiation oncologist doesn’t recommend a hypofractionated schedule and the person doesn’t have connective tissue disease, isn’t getting radiation to the lymph nodes, so on the surface looks like to be a good candidate, what would be your advice? Can a patient really advocate for a shorter schedule for him or herself?

Dr. Chirag Shah: So, first of all, absolutely. A patient should always advocate for themselves, and I think the first step is to ask their radiation oncologist or their clinician why they’re not felt to be a candidate for hypofractionation, and maybe there’s something that they didn’t see that may have been a reason. But if that’s not really the case, then I think they should absolutely advocate for themselves and if needed, even seek additional opinions about whether they really are a candidate for hypofractionated breast radiation.

Jamie DePolo: So a person could get a second opinion, say, if maybe their radiation oncologist wasn’t comfortable with it or perhaps maybe hadn’t read all the latest research. So a person could go get a second opinion?

Dr. Chirag Shah: Absolutely.

Jamie DePolo: Wonderful. Dr. Shah, thank you so much. I really appreciate your insights on this.

Dr. Chirag Shah: Thank you so much.