Combo Brachytherapy Improves Local Control in Cervical Cancer

Kate Johnson

April 28, 2015

BARCELONA, Spain — A combination of both interstitial (IS) and intracavitary (IC) brachytherapy for the treatment of locally advanced cervical cancer can improve disease control without increasing late morbidity compared with intracavitary brachytherapy alone, new data from the retro-EMBRACE study suggest.

"The new technique does not increase radiation dose to the bladder or bowel, and for local control, we have found that especially women with large tumors have a pronounced benefit of IC/IS brachytherapy," study investigator Lars Fokdal, MD, PhD, from Aarhus University Hospital, Denmark, told Medscape Medical News. "Based on our results, we do believe that the study will serve as benchmark for future image-guided adaptive brachytherapy with combined IC/IS."

The findings were presented here at the European Society for Radiotherapy and Oncology (ESTRO) 3rd Forum.

This study "shows how the best results may be obtained by properly using the newest technical developments in the field of brachytherapy," commented ESTRO president Philip Poortmans, MD, PhD, in a press release.

The next step is to teach these optimized techniques to all our other colleagues. Dr Philip Poortmans

"Now, the next step is to teach these optimized techniques to all our other colleagues who treat locally advanced cervical cancer but do not yet use interstitial techniques as an addition to intracavitary ones," he added.

Multicenter Retrospective Study

Retro-EMBRACE is a multicenter, retrospective analysis of image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer.

This analysis involved 12 institutions from six countries and included 300 patients from institutions that systematically combined IC/IS brachytherapy for more than 20% of patients (advanced adaptive [AD] group) and 310 patients from institutions that most commonly used IC brachytherapy alone (limited adaptive [LA] group).

Compared with the LA patients, more AD patients had combined IC/IS brachytherapy (47% vs 4%; P < .01) and MRI-based dose planning (97% vs 66%; P < .01).

Additionally, more AD patients than LA patients (17% vs 6%; P < .01) were treated with intensity-modulated radiation therapy (IMRT), which uses advanced technology to manipulate the shape and intensity of photon and proton radiation beams to conform to the shape of a tumor, and nodal boost (22% vs 13%; P < .01).

Although patients in the AD group had significantly larger tumors, with a high-risk clinical target volume (HR CTV) of 39 cubic centimeters compared with 33 in the LA group (P < .01), these AD patients received a significantly higher dose to at least 90% of their tumor (92 Gy vs 83 Gy; P < .01).

Despite receiving this higher dose to the tumor, AD patients did not receive a significantly higher dose to the rectum and sigmoid compared with LA patients, and there was a trend toward a lower bladder dose in the AD group (79 Gy vs 83 Gy; P = .07).

The study found that although local control at a median follow-up of 40 months was not significantly different between the two groups overall (P = .06), it did differ significantly when patients were analyzed according to tumor size, said Dr Fokdal.

"We had a group of patients with big tumors and an HR CTV of more than 30 cubic centimeters, and here we could see that these patients had a 10% increase in local control if they received AD rather than LA therapy (P = .02)," he said. "When we analyzed patients with small tumors, we saw no difference at all between those who had LA or AD therapy."

In terms of morbidity, the rate of late gastrointestinal and urinary bladder symptoms did not differ between groups. However, there was a trend toward higher vaginal morbidity in the AD group (for grade 3-4 morbidity, P = .08; for grade 2-5 morbidity, P = .1).

"Many of the AD patients were treated during the initiation of image-guided adaptive radiotherapy at each of the participating centers, when the vagina was not considered an organ at risk, and we did not have dose constraints for this organ," said Dr Fokdal. "We should consider the vagina an organ at risk in future image-guided adaptive brachytherapy and introduce vagina-sparing techniques in future treatments."

Caution in Interpreting Results

This is the first large international study to investigate the late side effects of combined IC/IS therapy, but "prospective studies should be performed to confirm this hypothesis," commented Nam Nguyen, MD, professor and chair of radiation oncology at Howard University, in Washington, DC, and president of the International Geriatric Radiotherapy Group. Approached for comments on the study by Medscape Medical News, he said the results should be interpreted with some caution because of an important confounding factor.

"It is intriguing to postulate that better planning with modern radiotherapy techniques such as IMRT and IGABT may allow radiation dose escalation and potentially improve cure rate without increasing the risk of complications," he told Medscape Medical News.

However, the study investigators attempted to compare patients treated with IC/IS with those treated with IC alone when, in reality, both treatment groups contained patients who received a mixture of therapies.

"Almost three times as many patients in the AD group also benefited from external beam radiation (IMRT), which is more sparing of healthy organs, such as the rectum and bladder. I would be more cautious about the conclusions," he said. "If the authors had excluded the patients who had IMRT (a confounding factor) and the results were the same, the conclusions would have been more valid. I would have concluded that AD may allow increased radiation dose to the clinical target volume, but these patients may also benefit from IMRT, based on the data presented."

Dr Fokdal's group is currently conducting the EMBRACE trial to test the results prospectively.

This study was conducted within the framework of the GEC-ESTRO Gynaecological Working Group recommendations. It received grants from Varian and Nucletron. Dr Fokdal, and Dr Nguyen, and Dr Poortmans have disclosed no relevant financial relationships.

European Society for Radiotherapy and Oncology (ESTRO) 3rd Forum: Abstract OC-0105. Presented April 25, 2015.


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