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At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.
These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.
Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.
Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.
The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.
The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.
“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”
Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
Efficacy and toxicity
At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.
The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.
“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.
The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.
The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.
For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.
Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
Room for improvement
“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.
However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.
In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.
Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
A benchmark for brachytherapy
“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.
With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.
Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.
“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.
“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”
The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.
SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.
At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.
These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.
Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.
Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.
The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.
The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.
“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”
Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
Efficacy and toxicity
At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.
The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.
“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.
The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.
The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.
For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.
Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
Room for improvement
“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.
However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.
In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.
Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
A benchmark for brachytherapy
“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.
With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.
Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.
“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.
“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”
The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.
SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.
At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.
These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.
Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.
Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.
The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.
The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.
“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”
Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
Efficacy and toxicity
At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.
The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.
“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.
The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.
The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.
For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.
Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
Room for improvement
“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.
However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.
In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.
Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
A benchmark for brachytherapy
“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.
With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.
Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.
“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.
“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”
The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.
SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.
FROM ESTRO 2020