Study compares treatment frequencies for one type of the disease

Host Amber Smith: Upstate Medical University in Syracuse New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host Amber Smith. Lung cancer remains the leading cause of cancer death in the United States, so efforts to improve survival can make a huge impact. Here to talk about his research on lung cancer treatment is Dr. Jeffrey Bogart. He's professor and chair of radiation oncology at the Upstate Cancer Center, and his lung cancer research was recently published in the Journal of Clinical Oncology. Welcome to "The Informed Patient," Dr. Bogart.

Jeffrey Bogart, MD: Thank you. Nice to talk.

Host Amber Smith: Your research focused on radiotherapy for patients with a small cell lung cancer, that's the type that is often caused by smoking, is that right?

Jeffrey Bogart, MD: That is correct. In fact, the majority of lung cancer is caused by smoking, but there are more and more folks, particularly women who have lung cancer without a history of smoking. So both small cell and non-small cell typically are smoking related, but almost universally small cell is smoking related.

Host Amber Smith: And what is radiotherapy?

Jeffrey Bogart, MD: So radiotherapy is high energy radiation that is focused out of a very state-of-the-art advanced machine that is a local treatment kind of similar to surgery, in a way, that can eliminate and kill off cancers when it's focused appropriately.

Host Amber Smith: And how long does it usually take?

Jeffrey Bogart, MD: Well, there's lots of different ways to give radiotherapy in lots of different situations.

So there are some patients where we do three or five treatments, and there's other patients where we do 35 or 40 treatments, over seven or eight weeks. Small cell lung cancer is a very special type of lung cancer, in that we have a few different options in terms of radiotherapy treatment. We have a lot of clinical experience and data going back 30 years in terms of looking at how to best treat small cell lung cancer with radiotherapy.

Host Amber Smith: Does radiotherapy actually get rid of the cancer cells?

Jeffrey Bogart, MD: That is absolutely the goal of the radiotherapy. The cancer cells, because they're growing and dividing more rapidly, are more likely to die off from the radiotherapy than the surrounding area. So while radiotherapy is not 100% effective, there's a very good chance to shrink down with the goal of completely eliminating the cancer.

Host Amber Smith: How do doctors determine how much radiotherapy is the right amount for each particular patient? Because it varies from patient to patient, right?

Jeffrey Bogart, MD: Most of the time it varies according to the clinical stage in the entity.

So for patients that have small cell lung cancer, there's two basic categories. One is extensive stage. That means that it's spread somewhere else in the body, outside of the lungs and outside of the chest. The other is called limited stage, and that's what we're talking about today. That means it's contained within the lung and the lymph nodes in the middle of the chest, what we call the mediastinum. We do have a lot of information on giving radiotherapy in that situation for limited small cell lung cancer, and that's the patient population that my trial addressed.

Host Amber Smith: I know we're gonna get into this with your trial, but how do you go about determining whether a big dose once a day, or splitting the dose in half, twice a day is going to work better?

Jeffrey Bogart, MD: Really the only way to know for sure is to do comparative trials. So the first modern trial that was done to look at that question in small cell lung cancer was done in the early 1990s. And that trial showed that if you give a smaller dose twice a day and finish in three weeks -- so that's basically twice a day, weekdays, so it's 30 sessions over 15 weekdays -- that was better than giving the same dose once a day, over five weeks, the same total dose. Accelerating the way that we give treatment actually had a fairly noticeable impact on how many patients were cured.

So what has happened in the last 30 years is the technology we have has allowed us to be more aggressive and give much higher doses of radiation than we used to give. So the two times a day to this, what we call standard dose, which is 45 gray or 4,500 units, we compared going up to 7,000 units, or 70 gray.

So we kept the standard, which was twice a day. We went for a full seven weeks. We had done several trials prior to this showing that we were able to give seven weeks of radiotherapy fairly safely, and it looked to be effective. We found that both regimens are fairly effective. The results we saw in this trial were better than results we've seen previously. Part of that is just better care as time goes along, better technology. But, the results were promising for patients, whether they got twice-a-day or once-a-day radiation.

Host Amber Smith: How many patients were involved in your study? And I'm assuming some of them came from Syracuse.

Jeffrey Bogart, MD: Yeah, so it was a national study, so we collaborated through our, what we call our cooperative group that is sponsored by the National Cancer Institute. So there were more than 700 patients on the trial, and I believe about 15 to 20 of them came from Upstate.

Host Amber Smith: How did you decide, or did patients have any say in which one they got, whether they got it once or or twice?

Jeffrey Bogart, MD: Well, the magic of doing these clinical trials is that we don't know the right answer, and patients have to help us, understanding that we don't know which is best, and allow us to assign one or the other. That's really the whole reason to do the trial, to determine which one is better. If we knew in advance, then we wouldn't be asking the question and doing the trial.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith. I'm talking with Dr. Jeffrey Bogart. He's professor and chair of radiation oncology at the Upstate Cancer Center, and in addition to taking care of patients, he's also involved in clinical research.

So you said there's not a big difference in survival, is that right?

Jeffrey Bogart, MD: That is correct. There was a prior trial done in Europe that suggested that the twice a day might be better than going to a higher dose once a day. Our trial found that going to the seven weeks was looked to be just as good, maybe slightly better numbers, but not significantly different than twice a day.

Host Amber Smith: When you are prescribing this for patients, can you take into consideration what's convenient for them? If both of them will work, but it's easier for them to just have it once a day? Can that help you in your decision making?

Jeffrey Bogart, MD: It's a good question because there's pros and cons to both approaches, right? One advantage of twice a day is that you get the treatment in, and it's done. For those that have once a day, they're also getting chemotherapy together with the radiation, which is important.

And we're looking in more detail at the trial now, but it may be more likely that you might need a treatment break or interruption because of the blood counts going down if you extend the treatment out over six or seven weeks, whereas you may be able to get through the treatment a little bit quicker without needing to stop if you do it twice a day.

Host Amber Smith: People with small cell lung cancer, are they all recommended for radiation? Is that pretty standard?

Jeffrey Bogart, MD: It's standard for patients that have the limited stage. Those that have more extensive disease, meaning that it's spread somewhere else in the body, there's a subset of those that get radiation. But for that patient population, the newest treatment is that we know that immunotherapy -- that's medication that stimulates the body's immune system to recognize and fight the cancer -- has been found effective to help with those patients.

We also just finished the clinical trial that we participated in, another national trial, that looked at whether or not immunotherapy would be beneficial for patients with limited stage disease. And that trial has completed, that's about 500 patients, but we don't yet have the results. And in that trial, patients could either get twice-a-day or once-a-day radiotherapy. So it was up to the patient and the physician in terms of the treatment.

Host Amber Smith: So you really have to think about all of the other treatments that are going to be part of this in addition to the radiotherapy, because you mentioned chemotherapy as well, and/or immunotherapy, right?

Jeffrey Bogart, MD: Absolutely. There've been a lot of advances in lung cancer. Most of the changes have been in the non-small cell lung cancer with what we call targeted agents looking at very personalized medicine. But we're beginning to do that in small cell lung cancer as well. And the first advance really was with immunotherapy for patients that have extensive stage disease.

What we're trying to do now is really determine which patients benefit the most from immunotherapy and maybe which patients would benefit more from other treatments.

Host Amber Smith: Now getting back to the study that you did, I'd like to ask you about the adverse events or the side effects. I think you were saying that there weren't more side effects from having more intensive radiation than with it spread out more. Is that right?

Jeffrey Bogart, MD: Overall, there was no major difference in side effects. The main thing we worried about is swallowing, because the esophagus runs down the middle of the chest. And most of the time with small cell lung cancer, there's lymph glands involved with the cancer that are near the esophagus. And if the esophagus gets irritated, that could cause difficulty swallowing and eating. It's generally temporary and manageable.

In the prior trial, the one from 30 years ago, those that got radiation twice a day, because it was more intensive, got more severe difficulty with swallowing an esophagitis. That was not the case for our trial. It was about the same on both what we call treatment arms. There may have been a small difference. We talked a little bit about the blood counts, and there probably were a few more patients that had difficulty recovering blood counts over time with the more prolonged radiotherapy. But there wasn't a significant difference.

Host Amber Smith: Now, based on the results of your study, which small cell lung cancer patients with limited small cell lung cancer might be candidates for the once a day versus twice a day?

Jeffrey Bogart, MD: It's a good question, and actually there's no particularly great answer right now. What we are doing right now is doing in depth subset analysis. So it may be that certain patients -- based on perhaps gender, or age, or other factors -- may do better with one versus the other. We're looking also at the extent of how big the cancer was, how extensive the involvement in lymph nodes was. So that's research that we're doing right now. We hope to present that in April in a European lung cancer meeting in Copenhagan.

Host Amber Smith: How long do you think it'll be before the results of your study are reflected in national guidelines?

Jeffrey Bogart, MD: There are national guidelines that are published called NCCN (National Comprehensive Cancer Network) guidelines. So, our trial will be part of those guidelines in helping physicians choose how to treat patients.

Host Amber Smith: Just how important is radiotherapy to the overall survival of someone with small cell lung cancer?

Jeffrey Bogart, MD: Radiotherapy has been shown to improve cure rates for small cell lung cancer, and it's one of the diseases where we have a lot of information, a lot of clinical data, showing that with the use of radiotherapy, patients do better. The likelihood of being alive five years down the road is much better with radiotherapy. So it's become standard, when there's disease limited to the chest, to use radiotherapy.

Host Amber Smith: Well, Dr. Bogart, thank you so much for making time to tell us about your research.

Jeffrey Bogart, MD: Pleasure. Thank you for having me.

Host Amber Smith: My guest has been professor and chair of radiation oncology, Dr. Jeffrey Bogart from the Upstate Cancer Center. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at Upstate.edu/Informed. This is your host, Amber Smith, thanking you for listening.