Recent clinical trial results show that reducing the dose and duration of radiation therapy for anal cancer may result in fewer side effects.
The study, called PLATO, is being conducted through the Leeds CRUK clinical trials unit at the University of Leeds and is funded by Cancer Research UK and Stand Up To Cancer. It consists of three clinical trials (ACT 3, 4, 5) aimed at optimizing radiotherapy treatment for patients with anal cancer.
The ACT 4 trial is the first clinical trial in the world to randomize patients between standard and low-dose treatments for anal cancer. The results of this short-term study were presented at the 2023 European Society for Radiation Therapy and Oncology (ESTRO) Congress, Europe’s largest radiotherapy conference.
The presentation was made by Dr. Alexandra Gilbert, Associate Professor of Clinical Oncology, University of Leeds. Although the ACT 4 arms have not been compared statistically, the PLATO team found that six months of low-dose radiation therapy resulted in fewer side effects, improved sexual function, and higher levels of cancer than patients receiving standard care. He detailed that he had observed that it had completely disappeared. dose treatment.
Both groups had high rates of complete cancer response at 6 months. This means that all signs of cancer have disappeared in response to treatment with both low-dose and standard-dose radiotherapy.
The PLATO ACT 4 presentation detailed short-term results up to 6 months. Further follow-up is needed to determine the impact of low-dose radiotherapy on local recurrence of anal cancer, the results of which will be published next year.
Professor David Sebag-Montefiore is a Principal Investigator at PLATO and an Academic Clinical Oncologist at the University of Leeds. “The side effects of radiotherapy treatment have a significant impact on the lives of patients, their friends and family, and the results of the ACT4 trial using low-dose radiotherapy are very encouraging,” he said.
“The current approach to anal cancer treatment is essentially ‘one-size-fits-all’, meaning that whether the tumor being treated is very small or very large, the dose of radiotherapy is the same. It sacrifices cure rates.” If we could offer a customized approach without compromising the cure rate, radiation therapy doses could be comparable, and patients wouldn’t suffer side effects unnecessarily.
“PLATO’s ACT4 trial results are an important step towards a personalized approach to anal cancer and a smarter, more compassionate treatment approach.”
patient quality of life
Anal cancer is a rare disease, with about 1,500 people diagnosed in the UK each year, but the incidence of the disease is expected to increase by 14% over the next 15 years.
The current standard treatment for anal cancer is chemoradiation. Although this method yields relatively high cure rates, it results in significant side effects. The most common side effects of radiation therapy include skin pain, diarrhea, incontinence, fatigue, vaginal irritation, and loss of sexual function.
The global standard of care for anal cancer has not changed for over 20 years. Current approaches are associated with significant short- and long-term side effects, and high-quality evidence is needed to determine the optimal dose of radiotherapy for tumors of various sizes and degrees of local spread.
Despite its rarity, we were able to successfully complete a clinical trial, providing important evidence that will help determine the best treatments for future anal cancer patients and help maintain their quality of life. was able to provide ”
Dr. Alexandra Gilbert, Associate Professor of Clinical Oncology, University of Leeds
ACT4 PLATO Trial
The PLATO team worked with colleagues across the UK to develop and introduce a new radiotherapy approach, intensity-modulated radiotherapy (IMRT).
IMRT reduces treatment side effects and allows different radiotherapy doses to be applied to visible cancers. This requires a higher dose, but at the same time a lower dose for surrounding lymph node areas that are at risk of containing cancer cells.
It also provides a basis for testing the individualization of radiotherapy doses delivered to visible tumors.
The purpose of the ACT4 trial is to determine whether low-dose, short-dose radiotherapy in combination with chemotherapy can reduce short- and long-term side effects of treatment and still achieve rates as high as local eradication of cancer. was to do It is achieved with a combination of standard-dose radiation therapy and chemotherapy.
The ACT 4 trial enrolled 163 patients with anal cancer up to 4 centimeters who had not spread to nearby lymph nodes. They were recruited from 28 locations in the UK from January 2017 to December 2020.
The current standard of care, determined by previous randomized trials, is a total dose of 50.4 Gy combining 28 sessions of outpatient radiation therapy over 5.5 weeks and the same duration of chemotherapy.
The shorter course of treatment assessed by ACT4 is 41.4 Gy combining 23 outpatient radiation treatments over 4.5 weeks and chemotherapy for the same duration.
Sarah Brown, Professor of Cancer Clinical Trial Methodology, said: “PLATO will work in Leeds and Leeds with experts in anal cancer, clinical trials, radiotherapy, cancer biology, data science, computation and image processing. It’s a great example of a ‘team science’ approach at work.” A comprehensive study design of three studies in one means that this can be done efficiently, and in the future we can take a step towards more individualized treatment. ”
The co-chairs of the ACT4 trial are Prof. Richard Adams (Cardiff University) and Dr. Mark Harrison (Mount Vernon Hospital). We have a broader clinical trials unit team and a trial management group that includes patient and public engagement representatives.
Dr Ian Fawkes, Executive Director of Research and Innovation, Cancer Research UK, said: “Anal cancer is a devastating disease and treatment is often associated with life-altering side effects. There is a real need for treatments that improve people’s quality of life.
“The PLATO trial is an excellent example of making smarter use of existing resources and using the latest advances in radiotherapy to target cancer cells and leave healthy cells intact.
“We are really pleased that judicious use of radiation therapy has minimized these side effects. I look forward to it.”
Encouraging Patients to Participate in Clinical Trials – Rosie’s Story
Rosie Sanderson was diagnosed with anal cancer in 2019 at the age of 61. She entered her PLATO trial as part of a randomized patient set.
Rosie began experiencing shortness of breath four years ago and was initially diagnosed with anemia due to anal bleeding after an examination by her GP. She attributed the symptoms to Rosie’s pre-existing illness, which she attributed to her. It is not uncommon for people to ignore cases of anal bleeding, sometimes believing it to be caused by other ailments such as hemorrhoids, diarrhea or constipation. But this is her one of the few early symptoms of anal cancer.
A colonoscopy and biopsy confirmed she had anal cancer, and she was referred to St. James, led by a team led by Professor David Sebag Montefiore.
Rosie immediately became interested in the possibility of participating in a clinical trial and consulted with her doctor. “I have always recognized the importance of clinical trials to improve the treatment of rare diseases, especially for diseases such as anal cancer,” Rosie said.
“It was clear from the beginning that participating in a clinical trial would not compromise my care. I was confident that my health would remain a priority during the trial.”
As part of PLATO ACT4, Rosie underwent standard dose radiotherapy for five and a half weeks. Because the trial was randomized, Rosie did not know which treatment she would receive at enrollment. Rosie also received chemotherapy as standard treatment for anal cancer.
She said, “About two to three weeks after starting the treatment, I started to really feel side effects such as pain and fatigue. I can’t go to the hospital anymore, before I start treatment,” he said. , I was a really healthy and active person. That loss of independence and constant fatigue was a big challenge for me. ”
Rosie was declared cancer-free in 2020, with a five-year follow-up planned. Her pain and fatigue disappeared a few weeks after her treatment ended, although she still suffers from long-term side effects. Rosie is still part of PLATO, and she continues to complete regular surveys to track long-term side effects and her health.
Rosie says: “Having experienced treatment for anal cancer, I fully understand how it would be helpful to have more treatment options. Future patients will not have to face so many side effects and treatment duration will be shorter. It’s really great to have the potential.”
“My advice to anyone considering joining a clinical trial is, ‘Go for it!’ Let your doctor know you’re interested,” Rosie said. I know the options available and can decide together if it’s right for me.”
“Clinical trials allow researchers and doctors to find better ways to help people, and it’s really nice to be a part of it.”