April 20, 2013
Treatment Of Cervical Cancer Outlined With Two New Studies
redOrbit Staff & Wire Reports - Your Universe Online
Two landmark radiotherapy studies demonstrating cervical cancer tumors can be effectively treated with specifically-adapted high doses will be presented this weekend at the 2nd Forum of the European Society for Radiotherapy and Oncology (ESTRO).
Treating cervical cancer with radiotherapy is problematic because the vagina receives a high dose of radiation, which can lead to symptoms such as vaginal dryness, vaginal narrowing and shortening with a loss of flexibility (stenosis), vaginal inflammation (mucositis), bleeding, or a hole in the wall of the vagina (vaginal fistula). The treatment can also adversely affect the bowel and bladder, the organization said.
However, image-guided brachytherapy delivers the radiotherapy to the tumor by placing a radioactive source inside an applicator. That applicator is then placed internally in the same area as the tumor, and then imaging — in the form of CT or MRI scans — is used at the same time as the treatment in order to delineate the tumor itself and the organs that could be adversely affected by the applicator. This allows radiation oncologists to measure and evaluate the tumor´s response to the treatment and adjust the dose accordingly while protecting nearby organs, ESTRO said.
Establishing A Clinical Benchmark For Brachytherapy
The first study, which will be presented on Saturday, investigates the relationship between the dose of radiotherapy and the impact it has on the vagina during brachytherapy for cervical cancer. It is an international, multi-center clinical trial known as EMBRACE and was led by Kathrin Kirchheiner, a PhD student in the Department of Radiotherapy at the Medical University of Vienna in Austria.
According to Kirchheiner, the researchers have thus far followed 523 patients in 19 facilities worldwide for an average of 14 months in the hopes their study will be able “to establish a benchmark for clinical outcome with regard to control of the tumor´s growth, patient survival, adverse effects of treatment and quality of life.”
Cervical cancer patients participating in the study underwent external beam radiotherapy, chemotherapy and MRI-guided brachytherapy, and the impact of the respective treatments and the condition of the vagina were assessed at the beginning of the study, then again every three months during the first year, twice during the second and third years, and once per year thereafter.
“Our results show that severe vaginal side-effects are rare,” Kirchheiner said. “The majority of patients are likely to experience mild to moderate (grade 1 or 2) vaginal morbidity in the first two years after the end of treatment. The most frequently reported symptom is vaginal shortening and narrowing in the upper vagina. We performed a dose response analysis to measure the relationship between the amount of dose delivered to the upper vaginal wall and the probability of vaginal morbidity and found that with increasing dose to this region, the probability for moderate vaginal morbidity increases significantly.
“This is important for patients because studies on their quality of life have shown that mild and moderate vaginal symptoms and associated sexual dysfunction can cause long-term distress in cervical cancer survivors, but until now a clear dose response relationship had not been established,” she added. “With the possibility of dose adaptation and optimization in image guided adaptive brachytherapy, a highly individualized and tailored treatment has become possible, comparable to the targeted, personalized therapies in medical oncology.”
Controlling Cervical Cancer Through MRI-Guided Brachytherapy
The second study is known as retroEMBRACE, which gathered data on nearly 600 patients in a dozen different institutions throughout Europe and Asia. This research was led by Kari Tanderup, an associate professor in the Department of Oncology at Aarhus University Hospital in Denmark, and the results will be reported Sunday at the ESTRO Forum.
“When using radiotherapy to treat cervical cancer there is a certain distribution of absorbed dose within the body and it is essential to know the dose level needed for local control of the tumor,” Tanderup will report during her presentation, according to the radiotherapy and oncology group. “However, there has been a wide range of brachytherapy schedules throughout the world with application of different dose levels for cervical cancer, and there has been limited evidence for a clearly defined dose response relationship.
“One of the reasons is that most cervical cancer brachytherapy experience has been based on planning on radiographs and not 3D imaging. With radiographs it is difficult to assess the dose to the tumor precisely, whereas with MRI or CT guided brachytherapy is it now possible to assess the dose to the tumor with much higher precision,” she added. “With the retroEMBRACE study it has been possible for the first time to assess a dose response relationship in a large number of patients in a multicenter setting. We looked at different dose levels and found a significant increase in local control with higher doses.”
In this study, cervical cancer patients were treated with external beam radiotherapy, chemotherapy and image-guided adaptive brachytherapy (IGABT) based on either MRI or CT scans. The amount of residual tumor (also known as high risk clinical tumor volume or HR CTV) was analyzed following external beam radiotherapy in order to guide IGABT treatment and target the residual tumor.
By taking the HR CTV into account, Tanderup explained, doctors and health care workers are able to individualize a brachytherapy treatment based on the patient and the tumor´s response — an approach known as “adaptive radiotherapy.”
"Our study shows very clearly that the higher the dose the better the tumor´s response to the brachytherapy for the entire patient population. It is possible to obtain local control in over 90 percent of patients with application of very high doses of over 90Gy,” she reported. “Brachytherapy is a very appropriate technique to obtain highly focused boost doses, and retroEMBRACE shows that it is actually possible to deliver doses greater than 90Gy for a significant fraction of the patients.
“Furthermore, the study also enables us to analyze results in patients with different risks of their tumors recurring or continuing to grow,” Tanderup said. “The retroEMBRACE study is important for the community because it establishes evidence for a dose response relationship in locally advanced cervical cancer; it shows that local control in over 90 percent of patients can be obtained with the use of MRI-guided brachytherapy; retroEMBRACE makes it possible for institutions to change their dose prescription in order to optimize the balance between local control and adverse side-effects; and it demonstrates that the adaptive target concept which has been developed for MRI-guided brachytherapy is robust in a multicenter setting.”