Abstract Purpose Upfront quality assurance (QA) is considered essential when starting a multicenter clinical trial in radiotherapy. Despite the long experience gained for external beam radiotherapy ...(EBRT) trials, there are only limited audit QA methods for brachytherapy (BT) and none include the specific aspects of image guided adaptive brachytherapy (IGABT). Methods and materials EMBRACE is a prospective multicenter trial aiming to assess the impact of (MRI)-based IGABT in locally advanced cervical cancer. An EMBRACE dummy run was designed to identify sources and magnitude of uncertainties and errors considered important for the evaluation of clinical, and dosimetric parameters and their relation to outcome. Contouring, treatment planning and dose reporting was evaluated and scored with a categorical scale of 1–10. Active feedback to centers was provided to improve protocol compliance and reporting. A second dummy run was required in case of major deviations (score <7) for any item. Results Overall 27/30 centers passed the dummy run. 16 centers had to repeat the dummy run in order to clarify major inconsistencies to the protocol. The most pronounced variations were related to contouring for both EBRT and BT. Centers with experience in IGABT (>30 cases) had better performance as compared to centers with limited experience. Conclusion The comprehensive dummy run designed for the EMBRACE trial has been a feasible tool for QA in IGABT of cervix cancer. It should be considered for future IGABT trials and could serve as the basis for continuous quality checks for brachytherapy centers.
The purpose of this study was to develop a novel quality assurance (QA) program to check the entire treatment chain of image-guided brachytherapy with dose distribution evaluation in a single setup ...and irradiation using a gel dosimeter.
A polymer gel was used, and the readout was performed by magnetic resonance scanning. A CT-based treatment plan was generated using the Oncentra planning system (Elekta, Sweden), and irradiation was performed three times using an afterloading device with an Ir-192 source. The dose-response curve of the gel was created using 6-MV X-ray, which is independent of the source beams. Planar gamma images on a coronal plane along the source transport axis were calculated using the measured dose as a reference, and the calculated doses were used in several error simulations (no error; 2.0 or 2.5 mm systematic and random source dwell mispositioning; and dose error of 2%, 5%, 10%, and 20%).
The dose-R
(spin-spin relaxation rate) conversion table revealed that the uncertainty and dose resolution of 6-MV X-ray were better than those of Ir-192 and also constant between the three measurements. With the 3%/1 mm criteria, there were statistically significant differences between each pair of settings except dose error of 2% and 5%.
This work depicts a simple and efficient end-to-end test that can provide a clinically useful tool for QA of image-guided brachytherapy. In this QA program, air kerma strength and dwell position setting could also be verified. This test can also distinguish between different types of error.
For medically inoperable endometrial cancer (MIEC), the volumetric target of image-guided brachytherapy (IGBT) techniques is not well established. We propose a high-risk CTV (HRCTV) concept and ...report associated rates of local control and toxicity.
For all MIEC patients receiving definitive external beam radiotherapy (EBRT) followed by MRI-based IGBT at a single institution, BT dose was prescribed to HRCTV defined as GTV plus endometrial cavity with a planning goal of a summed EQD2 D90 of ≥85 Gy. Freedom from local progression (FFLP) and overall survival (OS) were estimated via Kaplan Meier method.
Thirty two MIEC patients received EBRT followed by MRI-based IGBT between December 2015 and August 2020. Median follow up was 19.8 months. A total of 75% of patients had FIGO stage I/II disease, 56% endometrioid histology, and 50% grade 3 disease. OS was 73.6% (95% CI 57.8%-89.3%) at 12 months and 65.8% (95% CI 48.4%-83.2%) at 24 months. FFLP was 93.8% (95% CI 85.3%-100%) at 12 months and 88.8% (95% CI 86.6%-91.0%) at 24 months. 23 (72%) patients experienced no RT-related toxicity, while 2 of 32 patients (6%) experienced late grade 3+ toxicities (grade 3 refractory vomiting; grade 5 GI bleed secondary to RT-induced proctitis).
Patients with MIEC receiving definitive EBRT followed by MRI-based IGBT prescribed to the MRI-defined HRCTV demonstrated favorable long-term local control with an acceptable toxicity profile.
Recent widespread use of three-dimensional image-guided brachytherapy (3D-IGBT) has improved radiotherapy outcomes of cervical cancer dramatically. In 2018, the International Federation of Gynecology ...and Obstetrics (FIGO) staging system for cervical cancer was revised. However, the influence of the revisions on the stage distribution and outcomes of cervical cancers treated with 3D-IGBT remains unclear. Here, we retrospectively analyzed 221 patients with cervical squamous cell carcinoma treated with definitive radiotherapy using 3D-IGBT (median follow-up, 60 months). The stage distribution and outcomes were compared between the 2009 and 2018 schemas. Stage migration occurred in 52.9% of the patients. Patients classified with the 2018 criteria as stage IIICr had the highest proportion (43.8%) of migration, and were mainly from the 2009 stages IIB and IIIB. The 2009 and 2018 schemas showed comparable performance at stratifying 5-year overall survival (OS) and 5-year progression-free survival (PFS) for patients in stages IB–IVA. The 2018 criteria effectively stratified 5-year OS and PFS in the stage III substages. The 5-year OS and PFS for stage IIIC1r patients varied according to tumor T stage. These data provide evidence for the utility of the revised 2018 FIGO staging system in the clinical management of cervical cancers in the 3D-IGBT era.
Historically, external beam parametrial boost (EBPB) has been used in locally advanced cervical cancers to supplement radiation dose. However, it has become controversial in the era of image-guided ...brachytherapy. Modern 3D imaging and brachytherapy techniques have improved delineation and coverage of tumor. Outcomes with and without parametrial boost were analyzed.
Women with cervical cancer involving the parametria (clinically or radiographically) diagnosed between 2001 and 2017 were identified. Clinicopathologic and treatment features, survival and patterns of failure data were collected. Univariate and multivariable data analysis was performed to evaluate association of these variables, including parametrial boost, with local failure-free survival and overall survival. Competing risks analysis was performed for cumulative incidence of local failure, with death and other failures treated as competing events.
A total of 100 women were identified (median follow-up 26.8 mo). Forty-one (41%) received EBPB; these patients were less likely to have received magnetic resonance imaging, positron emission tomography, interstitial, or high-dose rate brachytherapy. Magnetic resonance imaging, positron emission tomography, dose rate, and treatment era were highly correlated (Cramer's V: 0.43 to 0.68, P<0.01). Two-year overall survival and local failure were 78% and 12% for the entire cohort. While the use of EBPB was not associated with any outcome on multivariable analysis, treatment year after 2009 was highly associated with improved outcomes in all models.
In this study, omission of EBPB did not compromise local control or survival in the modern era, supporting a decreased need for standardized use of parametrial boost.
Aim
Locally advanced cervical cancer is frequently treated using a combination of external beam radiotherapy and brachytherapy. Radiotherapy often leads to vaginal morbidity, which poses a ...significant problem. This study aims to analyze the impact of reducing ovoid loading on dosimetry.
Materials and methods
We analyzed forty-five CT-based intracavitary brachytherapy plans from fifteen patients. Three plan sets were created for the 45 applications: a standard loading plan (A), a plan with reduced ovoid loading (B), and a tandem-only loading plan (C). We generated Dose-Volume Histograms and recorded dose volume parameters for the three plan sets.
Results
The D90 for the Clinical Target Volume (CTV) did not show significant differences among the three plan sets (
p
= 0.20). The average D90 values for plans A, B, and C were 8.15 Gy, 8.16 Gy, and 7.4 Gy, respectively. No statistically significant differences were observed in D2cc bladder (
p
= 0.09) (average values: 6.8 Gy, 6.5 Gy, and 5.9 Gy for plans A, B, and C, respectively) and D2cc sigmoid (
p
= 0.43) (average values: 2.8 Gy, 2.6 Gy, and 2.4 Gy, respectively) among the three plan sets. However, there was a statistically significant difference in D2cc rectum (
p
< 0.001) (average values: 4 Gy, 3.3 Gy, and 1.8 Gy, respectively), as well as in vaginal dose points (
p
< 0.001).
Conclusion
Reducing ovoid loading significantly decreased the doses to vaginal dose points and the rectum without compromising the dose to the Clinical Target Volume (CTV). Therefore, in carefully selected cases, the adoption of tandem-only loading or reduced ovoid loading could be considered to minimize vaginal morbidity following high dose rate intracavitary brachytherapy.
Re-irradiation historically has been associated with unacceptable toxicity and limited benefit. Recent advances in radiotherapy can change the treatment paradigm to provide new salvage treatments for ...recurrences of cervical and endometrial cancer.
Image-guided brachytherapy is an effective method for salvaging central pelvic recurrence, although it has resulted in 20-25% severe late toxicity. Pelvic sidewall disease is not accessible to brachytherapy, so a combined modality approach with radical surgery and intraoperative radiotherapy is an alternative approach. Stereotactic body radiotherapy (SBRT) now provides the option of radical re-irradiation with local control rates of 50-80% and a low incidence of severe late complications.
Initial outcomes using SBRT and image-guided brachytherapy for re-irradiation of gynaecological cancer are encouraging. There has been good local control and acceptable toxicity. Further, large-scale studies are required to define optimal target doses and OAR limits.
To investigate the outcomes of definitive external-beam radiation therapy (EBRT) plus image-guided brachytherapy (IGBT) in patients with endometrial cancer (EC) unsuitable for surgery.
A total of 50 ...patients with inoperable EC were included. The patients received EBRT in a median dose of 45 Gy to the pelvis over 5 weeks. Thereafter, the patients received brachytherapy using tandem and ovoid applicators. High-risk clinical target volume (HR-CTV) and gross tumor volume in brachytherapy (GTVp) were defined by the assistance of patients' pre-IGBT magnetic resonance imaging.
The medical records of the 50 patients were analyzed. The main causes of inoperability were anesthesia contraindications, namely medical comorbidities and obesity. The median cumulative D90s (the minimum dose delivered to 90% of the volume) in EQD2 (equivalent dose in 2-Gy fractions) to the HR-CTV and GTVp were 72.9 Gy10 (range, 64.9 to 80.3) and 166.2 Gy10 (range, 123.0 to 189.8), respectively. Over a median follow-up period of 27 months, 8 of the patients died of cancer. The 2-year overall and cancer-specific survival rates were 75% and 83%, respectively. The cumulative incidences of pelvic and distant failure were 4% (n = 2) and 16% (n = 8), respectively. Gastrointestinal complications of grade 2 or above were noted in 2 patients (4%), and a grade 2 genitourinary complication was noted in one.
For patients with inoperable EC, EBRT followed by IGBT is an effective approach for achieving high local control without a high risk of complications.
The standard of care for locally advanced cervical cancer is external beam radiotherapy (EBRT) with simultaneous chemotherapy followed by an internal radiation boost. New imaging methods such as ...positron-emission tomography and magnetic resonance imaging have been implemented into daily practice for better tumor delineation in radiotherapy planning. The method of delivering radiation has changed with technical advances in qualitative imaging and treatment delivery. Image-guided radiotherapy (IGRT) plays an important role in minimizing treatment toxicity of pelvic radiation and provides a superior conformality for sparing the organs at risk (OARs) such as bone marrow, bowel, rectum, and bladder. Similarly, three-dimensional image-guided adaptive brachytherapy (3D-IGABT) with computed tomography (CT) or magnetic resonance imaging (MRI) has been reported to improve target coverage and reduce the dose to normal tissues. Brachytherapy is a complementary part of radiotherapy treatment for cervical cancer and, over the past 20 years, 3D-image-based brachytherapy has rapidly evolved and established itself as the gold standard. With new techniques and adaptive treatment in cervical cancer, the concept of personalized medicine is introduced with an enhanced comprehension of the therapeutic index not only in terms of volume (three-dimensional) but during treatment too (four-dimensional). Current data show promising results with integrated IGRT and IGABT in clinical practice and, therefore, better local control and overall survival while reducing treatment-related morbidity. This review gives an overview of the substantial impact that occurred in the progress of image-guided adaptive external beam radiotherapy and brachytherapy.
Abstract
We analyzed the local control (LC) of cervical squamous cell carcinoma treated by computed tomography (CT)-based image-guided brachytherapy (IGBT) using central shielding (CS). We also ...examined the value of tumor diameter before brachytherapy (BT) as a factor of LC. In total, 97 patients were analyzed between April 2016 and March 2020. Whole-pelvic (WP) radiotherapy (RT) with CS was performed, and the total pelvic sidewall dose was 50 or 50.4 Gy; IGBT was delivered in 3–4 fractions. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions, and distribution was modified manually by graphical optimization. The median follow-up period was 31.8 months (6.3–63.2 months). The 1- and 2-year LC rates were 89% and 87%, respectively. The hazard ratio was 10.11 (95% confidence interval: 1.48–68.99) for local recurrence in those with a horizontal tumor diameter ≥ 4 cm compared to those with < 4 cm before BT. In CT-based IGBT for squamous cell carcinoma, favorable LC can be obtained in patients with a tumor diameter < 4 cm before BT. However, if the tumor diameter is ≥ 4 cm, different treatment strategies such as employing interstitial-BT for dose escalation may be necessary.