The first large international study to investigate the late side effects of a combination of two forms of brachytherapy to treat cervical cancer has shown that the technique successfully delivers higher radiation doses to the tumor without an increase in treatment-related problems afterwards. These findings were presented at the 3rd ESTRO (European Society for Therapeutic Radiology and Oncology) Forum in Barcelona, Spain.

Brachytherapy is a type of internal radiotherapy that involves putting a radioactive source close to, or in the tumor. It is often performed after a CT or MRI scan has pinpointed the exact position of the cancer, so that the radiation treatment can be targeted precisely; this is called image-guided brachytherapy (IGBT). During intracavitary (IC) brachytherapy, the radioactive applicator is placed in the uterus and the vagina, while interstitial (IS) brachytherapy involves inserting needles directly into the tumor to deliver the radiation.

“Image-guided brachytherapy has transformed treatment for cervical cancer considerably, and dose adaptation and a combination of intracavitary and interstitial brachytherapy enable us to deliver radiation that is targeted at the tumor while avoiding other organs,” said Lars Fokdal, MD, PhD, a consultant at the Aarhus University Hospital, Denmark. “However, although some centers are using IC/IS brachytherapy, there are concerns that the technique might increase the likelihood of adverse side effects occurring 3 months or more after the end of radiation treatment.”

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Fokdal and colleagues in Austria, France, the United Kingdom, Slovenia, The Netherlands, and Ireland, enrolled 731 women with cervical cancer that had started to spread into nearby tissues (locally advanced) into the “retroEMBRACE” study. The study collected retrospective data on the use of IGBT to treat cervical cancer in nearly 800 women in 12 different countries.

The researchers analyzed data from a group of 300 patients from institutions that systematically used combined IC and IS brachytherapy on more than 20% of women, and a group of 310 patients from institutions where the most common treatment used was IC brachytherapy alone.

“We found that combined IC/IS brachytherapy enabled us to deliver higher doses to the tumor without delivering more radiation to the bladder and the bowel. This meant that there was no increased risk in severe adverse side effects 3 or more months later, but there is a better chance of a cure,” said Fokdal. “These results show that combined IC/IS brachytherapy is a good treatment and should serve as a benchmark for future brachytherapy in cervical cancer.”

After a median follow-up of 40 months, ranging from three to 163 months, the researchers found there was no significant difference in late bladder, gastro-intestinal or vaginal grade 2-5 morbidities between the two groups of patients.

Among the patients in the group more likely to receive IC/IS brachytherapy, 66% (versus 52% in the other group) received high-dose rate brachytherapy, and 47% versus 4% received the combined IC/IS treatment. In addition, 97% (versus 66%) of patients in the IC/IS group benefited from their radiation doses being planned with the aid of MRI scans.

Compared with the group least likely to receive IC/IS brachytherapy, the radiation dose in the IC/IS group of patients reached more of the targeted tumor area, with at least 90% of the tumors receiving a dose that was 9 Gy higher than in the non-IC/IS patients. However, these higher, targeted doses in the IC/IS group of patients did not result in higher doses of radiation to the bowel, and radiation doses to the bladder was an average of 4 Gy lower.