Combining External Radiation with High-dose Rate Brachytherapy Effective for Cervical Cancer, IAEA Study Confirms

A five-year long clinical trial conducted in seven low and middle-income countries has confirmed the safety and effectiveness of combining high doses of internal radiation therapy (Brachytherapy) with pelvic external beam radiation therapy in treating cervical cancer.

The IAEA’s study’s findings were presented at the plenary session of the 59th Annual Meeting of the American Society for Radiation Oncology (ASTRO).

The study’s co-author and director of the Division of Human Health at the IAEA, May Abdel-Wahab, said that cervical cancer is a leading cause of cancer death among women in the developing world.

Eighty percent of cancer patients live in low or middle-income countries. It is essential that we have data applicable to these global settings, she said.

A total of 601 patients with locally advanced cervical cancer participated in the study, which took place between September 2005 and May 2010. They came from India, Peru, South Africa, Brazil, Pakistan, Morocco and Macedonia.

Our trial demonstrates that combining pelvic radiation therapy with four fractions of 7 Gray (Gy) High-Dose Radiation (HDR) Brachytherapy is effective and safe for locally advanced cervical cancer, Abdel-Wahab said.

The patients received doses of pelvic external beam radiation therapy. They were randomly assigned to receive one of two brachytherapy schedules: half of them received four applications of 7 Gy (4 fractions X 7Gy) each, while the other half received two applications of 9 Gy (2 fractions X 9Gy) each. In addition, half of the patients in both the 7 Gy and 9 Gy groups received chemotherapy while the other half did not.

The results showed significantly superior tumour control in the group that received external beam radiation therapy plus the(4 fractions X 7Gy) (HDR) Brachytherapy, with 88 and 89 percent local control without and with chemotherapy. The rate of control in patients that received external beam radiation therapy plus the (2 fractions X 9 Gy) HDR Brachytherapy was 78 and 75 percent without and with the addition of chemotherapy.

The effect of chemotherapy did not influence overall survival, cancer-specific survival or tumour control in the cervix and surrounding region.

The findings that chemotherapy did not significantly affect survival or tumour control in this setting seem to be different than the results of the meta-analysis from the Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration, which found six percent differences in local control due to the effect of chemotherapy, explained Abdel-Wahab. However, it is important to note that our study was not powered to detect differences in local control that are less than 10 percent. In other words, the results of the two studies are not mutually exclusive.

The study has provided guidance for clinical teams treating women with cervical cancer and has showed the feasibility of conducting global clinical trials, including in countries where access to research is more difficult.

The trial gives physicians data-supported guidance from a large, randomized study on what to expect in terms of outcomes if a regimen of two, 9-Gy fractions is used in resource-constrained settings, Abdel-Wahab said.


Brachytherapy is a form of internal radiation therapy, by which a radioactive source is placed close to the tumour, either directly adjacent to it or inside the tumour itself. This procedure delivers a high dose of radiation to the target with only a minimal dose affecting the surrounding tissues. It is often used alone or in combination with external beam radiotherapy for gynecological cancers, prostate, breast, soft tissue sarcomas, some head and neck tumours and skin cancers.

Brachytherapy can be administered in a low dose rate (LDR), which utilizes Caesium and Iridium sources, among others. In this technique, an ‘applicator’ is placed in the cavity or inside the tumour and the source is loaded into the applicator, once the patient is in a shielded room. They remain in isolation until the source is removed (usually 12-24 hours). This process often requires hospital admission. It can also be given in a high dose rate (HDR), where the applicator is loaded with high activity, miniaturized sources of 60Cobalt or 192Iridium, which allows a dose rate greater than 12 Grays per hour, accounting for short times of treatment. For this reason, HDR can be administered as an outpatient treatment.

Source: International Atomic Energy Agency