NEW STUDY. Patients who have undergone pelvic radiotherapy may live with low-grade chronic inflammation of the lower intestine at least 20 years after their cancer treatment. This has been shown in a new study by researchers at the University of Gothenburg.
Radiotherapy is often necessary to cure or slow down a cancer. Even though today’s radiotherapies feature a high level of precision, healthy tissue in and around the radiation field is still affected. This study highlights a previously unknown side effect of radiotherapy to the lower abdomen.
The mucous membrane of the large intestine is normally protected against contact with bacteria in feces by a thin barrier of mucus. In the current study, researchers at the University of Gothenburg have shown that radiotherapy to the pelvic area affects this thin layer of mucus, allowing bacteria to come into contact with cells on the surface of the intestine. This could be a reason for the low-grade inflammation that the researchers also found in intestines that had been exposed to radiotherapy several years previously.
“It can be hard to detect low-grade inflammation,” says Sravani Devarakonda, a researcher at the University of Gothenburg’s Sahlgrenska Academy and lead author of the study. “This is the first time researchers have been able to show with certainty that this is happening in cancer survivors, a long time after pelvic radiotherapy has ended. We saw signs of low-grade inflammation as late as twenty years after radiotherapy.”
The study was carried out in broad collaboration between clinical and basic science researchers at the University of Gothenburg, Sahlgrenska University Hospital, and Karolinska Institutet. The results of the study have been published in the journal eBioMedicine.
Common intestinal problems
It is common for those who have received radiotherapy for cancer of the cervix, prostate, or rectum, for example, to experience intestinal symptoms many years after completing their treatment. The severity ranges from tenesmus (a feeling of not having emptied the bowels properly despite multiple toilet visits), to very frequent diarrhea (fifteen times a day or more).
The study is based on samples from 28 people, including 24 cancer survivors. Four of the subjects had not undergone radiotherapy and served as a control group. Among the subjects, the shortest time since radiotherapy was two years and the longest time was twenty years. The median was five years between the end of radiotherapy and intestinal biopsy.
“Our study subjects included both patients who had received traditional radiotherapy and those who had the more targeted form, IMRT,” adds Cecilia Bull, an associate professor at the University of Gothenburg’s Sahlgrenska Academy who led the research cooperation behind the study. “We saw low-grade inflammation in both groups. The damage to the surrounding tissue can be limited by IMRT, but there are still long-term inflammatory changes.”
Maintain intestinal health
The next step for the researchers will involve finding out whether this low-grade inflammation after radiotherapy causes some of the intestinal symptoms often seen in these cancer survivors and, if so, which symptoms are due to the inflammation.
Research is already being carried out to find ways of strengthening the intestines’ resistance to radiotherapy, so that long-term symptoms which affect quality of life can be alleviated or even prevented entirely. In an extensive study involving more than 300 patients, researchers are trying to strengthen the protective mucosal barrier by adding extra dietary fiber to the diet before beginning radiotherapy.
The study (FIDURA, dietary Fiber Intake DUring pelvic RAdiotherapy) is a randomized, placebo-controlled study that aims to build up knowledge for use during pelvic radiotherapy to maintain intestinal health. The study is part of Rebecca Ahlin’s doctoral project, with Maria Hedelin acting as main supervisor. In the study, patients have been randomized to capsules with or without fiber supplements, which they started taking shortly before the actual radiotherapy and up to one month after. They have also received dietary advice to increase their fiber intake, using a mobile app and surveys to record what they eat and providing answers about their intestinal health. The study also includes taking blood and stool samples. The final follow-up takes place one year after the end of radiotherapy.
“We already know that dietary fiber can strengthen mucus protection in the intestine,” says Cecilia. “The findings from the study we have now published – Biopsies in cancerSURVivors, or BIOSURV for short – lead us to believe that FIDURA has a good chance of making a difference.”
Many researchers have contributed
The study would not have been possible without the contributions from researchers and healthcare professionals at Sahlgrenska University Hospital. It also required collaboration between clinical and basic science researchers with expertise within oncology, gastrointestinal diseases, and mucosal biology. Additionally, important contributions were made by Sahlgrenska Academy’s Proteomics Core Facility.
The idea of looking at long-term changes in the intestinal wall after radiotherapy via a biopsy study at Sahlgrenska University Hospital was initiated by Gunnar Steineck, an oncology physician and professor of epidemiology at the University of Gothenburg’s Sahlgrenska Academy, together with Karin Bergmark, a university hospital consultant, gynecological oncologist, and associate professor of oncology. Karin has built up the Pelvic Cancer Rehabilitation Unit, a clinic that is primarily for women who have suffered late effects following pelvic radiation due to cancer.
“Gunnar and I have been working together for decades on questionnaires for cancer survivors to map their perceived intestinal problems after receiving radiotherapy,” she explains.
Later in his career, Gunnar became particularly interested in the pathological processes that lie behind long-term intestinal dysfunction after radiotherapy, for which we only have very limited knowledge. Sadly, he passed away this summer, but witnessed the results of the study.
“As an oncologist, Gunnar noticed the clear intestinal problems that patients experienced after radiotherapy,” concludes Cecilia. “He was enthusiastic about the collaboration with basic science researchers, which would provide more mechanistic answers and hopefully result in preventing problems.”
Title: Low-grade intestinal inflammation two decades after pelvic radiotherapy; https://doi.org/10.1016/j.ebiom.2023.104691
BY: ELIN LINDSTRÖM
