A common side effect of radiation treatment for prostate cancer can be reduced by factoring in anatomy and the dose of therapy into a new treatment formula, according to the results of a large population-based study.
Men with prostate cancer who have shorter rectums and those who receive intermediate to high doses of radiation are at higher risk of late rectal bleeding, and should receive tailored treatments to prevent the complication, according to a study presented at the American Association of Physicists in Medicine Annual Meeting (Abstract TH-AB-304-1).
“The risk of late rectal bleeding increases with increasing rectal volume receiving even mild dose spillover—above about 65 percent of the typical prescription dose,” the study's senior author, Joseph Deasy, PhD, Chair of the Department of Medical Physics at Memorial Sloan Kettering Cancer Center (MSKCC), explained in an interview.
“Patients with shorter rectums have a larger risk, all other factors being equal, of late rectal bleeding. By reducing the dose to the edge of the area being irradiated in men with shorter rectums, possibly using better treatment image guidance, we can significantly reduce the risk of late-stage rectal bleeding.”
Confirms Importance of Dose
Asked for his perspective for this article, Howard Sandler, MD, Professor and Chair of the Department of Radiation Oncology at Cedars-Sinai Medical Center in Los Angeles, said the study confirms that dose is important for late rectal bleeding. “The model might be useful to practicing radiation oncologists as a tool to guide their plan to reduce the risk of late rectal bleeding.”
Deasy said that as many as 10 percent of men who have radiation therapy for prostate cancer suffer from rectal bleeding that can occur several months after the treatment, and about five to 20 percent of prostate cancer patients have late rectal bleeding even years after treatment.
“Chronic late bleeding occurs over an extended time—years after radiation therapy. It can be treated, but it can be painful, uncomfortable, and reduces quality of life of patients. We can change treatments to reduce the risk of bleeding.”
1,001 Men from 5 Institutions
At the AAPM meeting, Maria Thor, PhD, a post-doctoral fellow at MSKCC, presented the results of the study from five institutions that analyzed 1,001 men who received various types of radiation therapy for prostate cancer. Rectal cross-sectional area, length, and volume were compared between patients who did and did not have late rectal bleeding.
Patients with the late effect were found to have had significantly smaller and shorter rectums than non-late rectal bleeding patients, and a larger volume of the rectum was exposed to a medium to high dose of radiation.
“We found that for patients with a larger cross-sectional area on imaging showing the rectum and prostate in square centimeters, those with smaller rectums had a higher risk of having this complication,” Deasy said.
“We also found the relative volume of rectum exposed at about 45 Gy was at increased risk—This is a new result because it was thought that only the very highest doses of radiation increased the risk of complications.”
The probability of bleeding was able to be predicted using a mathematical formula during treatment planning to minimize the risk. “This formula potentially could be put into treatment planning systems that are routinely used,” Deasy said.
If the model continues to hold up to the criticism of peer-review as part of publication, “then we need to work with the treatment-planning company vendors, and possibly the FDA as well, to put the model into the clinical environment as a decision support tool for planners and physicians.”
Radiation technique matters as well, he continued. In comparing three-dimensional conformal radiotherapy versus more modern intensity-modulated radiotherapy (IMRT), the team found a larger rectal volume of radiation among those receiving intermediate-high doses in 3D-conformal radiotherapy.
“Newer technology, IMRT, is effective at reducing this problem. We don't have a complete picture of why that is the case, although we know it is related to a reduced high dose to the rectum.”
Affirmation for IMRT
Sandler agreed that the study is another affirmation of the use of IMRT. “The principle is that the more radiation a normal structure gets, the more likely the patient will have side effects. We have worked hard over the last 20 years to improve the therapeutic ratio of radiation, to continue to provide radiation to the tumor and less radiation to normal tissues. But this is still complex.
“We have developed useful metrics about the risks of side effects based on the shape of radiation dose curves. But sometimes there is a tradeoff. We may give a large dose to a small area, or a low dose to a large volume of area.”
There are also individual patient factors to consider. “We can give the same treatment and one patient has complications, and another one does not,” he said.
The group at MSKCC has taken a different approach to accurately assessing the risk of complications, Sandler continued: “They were able to predict the risk of late rectal bleeding in about 15 percent of patients. The sample size of the study is good, and there are a good number of events.”
The results are similar to previous studies in that more radiation and a larger volume of the dose led to a higher risk of side effects.
“The utility of the information is that a practicing physician could potentially use their formula to predict the risk of late rectal bleeding,” Sandler said. “If the risk is above an acceptable threshold, the radiation oncology team could improve the plan to get a lesser dose to the rectum. For patients with a short rectum, we can work harder to make up for that by improving the dose distribution of radiation.”
Sandler added: “When I plan a case, I mostly focus on the high doses to the rectum. I usually don't emphasize instructions on low doses, but with this observation, I might consider low doses as important as well.”
Deasy said: “We can potentially modify the details of dose distributions as they are now generated by using treatment plan optimization. This optimization is performed by the computer using mathematical algorithms, to find the best treatment plan that has the desired dose characteristics as translated into mathematical terms.”
Also asked for her opinion, Colleen A. F. Lawton, MD, a former President of the American Society for Radiation Oncology, who is Professor and Vice Chair of the Department of Radiation Oncology at Medical College of Wisconsin, said: “The data says we need to pay attention to mid-range doses of radiation and the length of the patient's rectum. We always knew that on the high-dose end we needed to be careful in the rectum. Here's some science that proves that this is the right thing to do in using a mid-range dose of radiation in addition to the high dose.
“This is the first information I have seen about shorter rectums, and it makes sense,” she continued. “If a rectum has a smaller volume with shorter length, there is a higher risk of complications than a rectum with larger volume due to the longer length.”
Lawton agreed that this new formula could be very helpful for radiation oncologists in the community. “The simple thing would be to plug the formula into the planning system on the front side of the radiation plan. If a patient has a risk of rectal bleeding at a certain level, it will tell you what the V50 should be.”
Or a radiation oncologist could use the formula on the backside of the plan. “Based on the plan generated, if the patient has a certain risk of late rectal bleeding, then you could use the formula to get the V50 down.”
She added: “We all want our patients to avoid late complications. This data helps us in planning to reduce significant late rectal bleeding.”
Deasy said that as more comprehensive datasets and analyses are brought forward, “we can expect some updating of well-accepted dose-volume tolerance guidelines.”