MRI-based Cervical Cancer Brachytherapy Research Articles

Evaluating outcomes and toxicities for a newly implemented MRI-based brachytherapy program for cervical cancer

ObjectiveWe report an updated analysis of the outcomes and toxicities of MRI-based brachytherapy for locally advanced cervical cancer from a U.S. academic center. MethodsA retrospective review was performed on patients treated with MRI-based brachytherapy for cervical cancer. EBRT was standardly 45 Gy in 25 fractions with weekly cisplatin. MRI was performed with the brachytherapy applicator in situ. Dose specification was most commonly 7 Gy for 4 fractions with optimization aim of D90 HR-CTV EQD2 of 85–95 Gyα/β=10 Gy in 2 implants each delivering 2 fractions. ResultsNinety-eight patients were included with median follow up of 24.5 months (IQR 11.9–39.8). Stage IIIA-IVB accounted for 31.6% of cases. Dosimetry results include median GTV D98 of 101.0 Gy (IQR 93.3–118.8) and HR-CTV D90 of 89 Gy (IQR 86.1–90.6). Median D2cc bladder, rectum, sigmoid, and bowel doses were 82.1 Gy (IQR 75.9–88.0), 65.9 Gy (IQR 59.6–71.2), 65.1 Gy (IQR 57.7–69.6), and 55 Gy (IQR 48.9–60.9). Chronic grade 3+ toxicities were seen in the bladder (8.2%), rectosigmoid (4.1%), and vagina (1.0%). Three-year LC, PFS, and OS were estimated to be 84%, 61.7%, and 76.1%, respectively. ConclusionMRI-based brachytherapy demonstrates excellent local control and acceptable rates of high-grade morbidity. These results are possible in our population with relatively large volume primary tumors and extensive local disease.

Can We Avoid Ureters as Organs at Risk With MRI-Based Brachytherapy for Cervical Cancer? A Dosimetric Feasibility Study

Ureteral stenosis (US) is an underreported complication of brachytherapy for cervical cancer, with limited data regarding dose constraints to reduce risk of toxicity. Previous work from our institution demonstrated that an EQD2 ≥ 77 Gy to 0.1 cm3 of ureter correlated with development of US. We sought to determine whether we can reduce ureter dose EQD2 ≤77 Gy while maintaining similar HR-CTV coverage. We also sought to determine if anatomical factors would limit achieving ureter dose constraints.We identified patients with locally advanced cervical cancer treated with external beam radiation therapy plus HDR MRI-guided brachytherapy boost without hydronephrosis at diagnosis who had single or bilateral ureter dose EQD2 ≥ 77 Gy to 0.1 cm3, regardless of subsequent US. Replan was attempted for each individual brachytherapy fraction, aiming to achieve HR-CTV D90 ≥ 80-85 Gy without significant reduction in coverage, while maintaining rectal D2cc ≤65 Gy, bowel D2cc ≤65-70 Gy, sigmoid D2cc ≤70 Gy, and bladder D2cc ≤80 Gy. Distance of each ureter from lateral margin of HR-CTV and tandem were recorded, with mean values calculated on a per patient basis. Dependent samples T-test was performed to compare highest ureteral dose from original plan to replan ureteral dose and original plan HR-CTV D90 to replan HR-CTV D90. Independent samples T-test was performed to compare the mean distance of closest ureter to HR-CTV and tandem in patients for whom ureteral dose reduction was feasible to those for whom reduction was not feasible.25 patients met inclusion criteria, with all patients receiving 45 Gy in 25 fractions to the pelvis plus/minus paraaortic lymph nodes and 20 of 25 patients receiving mean parametrial dose of 5.4 Gy. Replan meeting ureteral dose of ≤77 Gy was feasible in 18 of 25 patients, with significant reduction in highest mean ureteral dose from 85.3 Gy to 76.7 Gy (P < 0.001). Mean original plan HR-CTV dose of 85.06 Gy decreased by 0.94 Gy to replan dose of 84.12 Gy in successfully replanned patients. Mean distance of closest ureter to HR-CTV margin was 1.5mm in patients for whom achieving ureter dose constraints was not feasible compared to 8.2mm for patients for whom replan was feasible (P = 0.038). Mean distance of closest ureter to tandem was 14.5mm for patients whom achieving ureter dose constraints was not feasible compared to 24.7mm for patients for whom replan was feasible (P < 0.001). Replan achieved ureter dose ≤77 Gy in the majority of patients who experienced US (56%), and 100% of unilateral US cases occurred in the ureter closest to HR-CTV.When ureters are contoured, optimization to reduce ureter dose to ≤77 Gy is feasible, potentially allowing for reduction in US risk without significant compromise in HR-CTV D90. Anatomic variation of ureter position may impact this optimization. Ureters may be considered as potential organs at risk during MRI-based brachytherapy treatment if visualization is feasible to reduce risk of US.S.A. Koerner: Stock; Novavax, Pfizer, Inovio Pharmaceuticals, Ocugen, Teladoc, ADC Therapeutics, CVS, Viatris Inc. T. Baig: None. H. Kim: None. J.L. Rodriguez-Lopez: None. A. Keller: None. S. Beriwal: None.

Ureteral stenosis after 3D MRI-based brachytherapy for cervical cancer – Have we identified all the risk factors?

Background and purposeUreteral stenosis (US) is a known complication from image-guided brachytherapy (IGBT); however, no dosimetric parameter has been associated with ureteral toxicity. We aimed to report the rate of late grade ≥3 US after MRI-based IGBT, and to identify clinical factors and dosimetric parameters predictive for US. Materials and methodsA retrospective review was performed on all cervical cancer patients treated with MRI-based IGBT between 2007 and 2017. Late grade ≥3 US was recorded according to CTCAE 4.03. The minimum dose to the maximally irradiated 0.1 cm3 of ureter (D0.1cm3) was extracted from dose-volume histograms. Binary logistic regression was performed to identify predictors of late grade ≥3 US. Results242 patients with a median follow-up of 35.8 months (IQR, 19.2–60.8) were identified. Late grade ≥3 US occurred in 18 patients, and the actuarial 3-year rate was 7.3% (95% CI 3.3–11.3). After excluding patients with pre-existing hydronephrosis, late grade ≥3 US occurred in 11 patients with an actuarial 3-year rate of 4.4% (95% CI 1.7–7.1). Ureters with D0.1cm3 ≥77 Gy had a 28.6% incidence of late grade ≥3 US compared to 7.5% in those with D0.1cm3 <77 Gy (OR 2.39; 95% CI 1.23–4.65; p = 0.01). The incidence of late grade ≥3 US was 33.3%, and 40.0% for ureters receiving ≥85 and ≥90 Gy, to D0.1cm3, respectively. ConclusionAfter MRI-based IGBT, there is an estimated 4.4% risk of developing late grade ≥3 US among patients without pre-existing hydronephrosis. Ureteral dose ≥77 Gy to D0.1cm3 correlates with development of late grade ≥3 US.

Risk of Ureteral Stenosis after 3D MRI-Based Brachytherapy for Cervical Cancer

The use of image-guided 3D conformal brachytherapy for cervical cancer has led to improved tumor local control as a Result of the ability to dose-escalate. However, some critical organs, like the ureters, are hard to visualize in modern imaging, and these structures may be at risk of severe complications. Hence, we sought to report the rate of late grade ≥3 ureteral stenosis after 3D MRI-based brachytherapy for cervical cancer.

Single-Institution Experience in 3D MRI-Based Brachytherapy for Cervical Cancer for 239 Women: Can Dose Overcome Poor Response?

Recent Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology guidelines recommend that the dose to 90% (D90) of the high-risk clinical target volume (HRCTV) in cervical cancer be at least 85Gy, with higher doses for poor response to radiation therapy. A retrospective review of brachytherapy delivered at a single institution was evaluated for dosimetry and outcomes. Significance of tumor parameters on local control was evaluated with Kaplan-Meier and univariable and multivariable Cox regression analysis. Correlations were determined with a linear regression model. A total of 239 women underwent high-dose-rate brachytherapy for cervical cancer between 2007 and 2018 with evaluable dosimetry. Median follow-up was 28.6months. The median prescribed dose was 27.5Gy in 5 fractions, with a median HRCTV D90 of 83.9Gy (range, 81.9-85.7Gy), HRCTV volume of 31cm3 (range, 14.9-121.9cm3), and treatment time of 51days (range, 36-83days). Local control for the entire cohort at 5years was 90.8%. Local control was worse with adenocarcinomas, HRCTV >40cm3 at brachytherapy, requirement for a higher brachytherapy dose, and treatment >51days. On multivariable analysis, local control was worse with adenocarcinoma (hazard ratio, 4.141; 95% confidence interval, 1.498-11.444; P=.006) and HRCTV >40cm3 (hazard ratio, 3.640; 95% confidence interval, 1.316-10.069; P=.013). HRCTV EQD2 D90>85Gy did not statistically improve outcomes for any subset. The 2-year progression-free survival for HRCTV >40cm3 was 66.2% versus 84.1% if ≤40cm3(P<.001). Overall survival was predicted by HRCTV and overall treatment time in multivariable analysis. For women with HRCTV ≤40cm3, overall survival at 2years was 90.4% versus 68.5% if >40cm3(P<.001). Local control was excellent with magnetic resonance imaging-based planning in the entire cohort of patients. A poor response to external beam radiation (larger HRCTV) and adenocarcinoma histology predicted for worse local control despite association with higher brachytherapy prescription. Women with these riskfactors face higher rates of extrapelvic progression and poorer overall survival.

Single-Institution Experience in 3D MRI-Based Brachytherapy for Cervical Cancer for 230 Women: Can Dose Overcome Poor Response?

Brachytherapy is an essential component of the treatment of locally advanced cervical cancer; recent GEC-ESTRO guidelines recommend that the dose to 90% (D90) of the high-risk clinical target volume (HRCTV) be at least 85Gy with even higher doses for poor response to external beam radiation. A retrospective review of brachytherapy plans delivered at a single institution were evaluated for dose parameters and local control following treatment. The HRCTV D90 was retrieved from all plans. Time to local failure was defined as time to event from completion of the last brachytherapy fraction. Significance of tumor parameters on local control was evaluated with univariate and multivariable Cox regression analysis. Correlations were determined with a linear regression model. A total of 230 women underwent high dose-rate brachytherapy for cervical cancer between 2007 and 2016 with evaluable dosimetry. Median follow up was 35.1 months. The median prescribed dose was 27.5Gy/5fx with a median HRCTV D90 of 83.7Gy (range: 74.8-93.5Gy), HRCTV volume of 31cc (range: 14.91-83.76cc), and treatment time of 7.1 weeks. Local control for the entire cohort at 3 years was 90.1%. Factors significantly correlated with higher rates of local failure were: HRCTV volume per cc increase (HR 1.047 [95%CI 1.017-1.078, p=0.002] and adenocarcinoma histology vs squamous (HR 2.773 [95%CI 1.148-6.698], p=0.023). Three-year local control for tumors < 31cc and ≥ 31cc, 3-year local control rates were not statistically different (93.5% vs 86.7%, p=0.055) but when 40cc was used as a cutoff, 3-year local control was 92.6% vs 82.2%, p=0.010. Adenocarcinomas had worse 3-year local control vs squamous cell carcinomas: 83.5% vs 91.7%, p=0.018. On multivariable analysis, HRCTV volume per cc increase (HR 1.044 [95%CI 1.014-1.075], p=0.004) and adenocarcinoma histology (HR 2.597 [95%CI 1.071-6.297], p=0.035) were both predictive of local failure. HRCTV dose at multiple thresholds (85, 90, 95Gy) did not predict for local control. There was a positive correlation between higher HRCTV volume and higher prescribed dose (R2 = 0.131, p<0.001). Adenocarcinomas were also significantly associated with higher prescribed brachytherapy dose (p=0.009). Women with HRCTV < 40cc had 3-year progression-free survival (including distant metastases) of 80.9% vs. 63.7% for ≥ 40cc (p=0.007). This translated to three-year overall survival for women with HRCTV < 40cc of 80.8% vs 61.0%% for ≥ 40cc (p=0.002). Local control is excellent with MRI based planning in the entire cohort of patients. Our data suggest that a poor response to external beam radiation (larger HRCTV volume) predicted for worse local control despite a higher brachytherapy dose delivery. These poor responders are also at higher risk of overall progression and death and may require additional intervention to mitigate this risk.

3D MRI-Based Brachytherapy for Cervical Cancer: Can Dose Overcome Response?

3D MRI-Based Brachytherapy for Cervical Cancer: Can Dose Overcome Response?

Deformable image registration–based contour propagation yields clinically acceptable plans for MRI-based cervical cancer brachytherapy planning

PurposeTo study the dosimetric impact of deformable image registration–based contour propagation on MRI-based cervical cancer brachytherapy planning. Methods and MaterialsHigh-risk clinical target volume (HRCTV) and organ-at-risk (OAR) contours were delineated on MR images of 10 patients who underwent ring and tandem brachytherapy. A second set of contours were propagated using a commercially available deformable registration algorithm. “Manual-contour” and “propagated-contour” plans were optimized to achieve a maximum dose to the most minimally exposed 90% of the volume (D90) (%) of 6 Gy/fraction, respecting minimum dose to the most exposed 2cc of the volume (D2cc) OAR constraints of 5.25 Gy and 4.2 Gy/fraction for bladder and rectum/sigmoid (86.5 and 73.4 Gy equivalent dose in 2 Gy fractions [EQD2] for external beam radiotherapy [EBRT] + brachytherapy, respectively). Plans were compared using geometric and dosimetric (total dose [EQD2] EBRT + brachytherapy) parameters. ResultsThe differences between the manual- and propagated-contour plans with respect to the HRCTV D90 and bladder, rectum, and sigmoid D2cc were not statistically significant (per-fraction basis). For the EBRT + brachytherapy course, the D2cc delivered to the manually contoured OARs by the propagated-contour plans ranging 98–107%, 95–105%, and 92–108% of the dose delivered by the manual-contour plans (max 90.4, 70.3, and 75.4 Gy for the bladder, rectum, and sigmoid, respectively). The HRCTV dose in the propagated-contour plans was 97–103% of the dose in the manual-contour plans (maximum difference 2.92 Gy). Increased bladder filling resulted in increased bladder dose in manual- and propagated-contour plans. ConclusionsWhen deformable image registration–propagated contours are used for cervical brachytherapy planning, the HRCTV dose is similar to the dose delivered by manual-contour plans and the doses delivered to the OARs are clinically acceptable, suggesting that our algorithm can replace manual contouring for appropriately selected cases that lack major interfractional anatomical changes.

How one institution overcame the challenges to start an MRI-based brachytherapy program for cervical cancer.

PurposeAdaptive magnetic resonance imaging (MRI)-based brachytherapy results in improved local control and decreased high-grade toxicities compared to historical controls. Incorporating MRI into the workflow of a department can be a major challenge when initiating an MRI-based brachytherapy program. This project aims to describe the goals, challenges, and solutions when initiating an MRI-based cervical cancer brachytherapy program at our institution.Material and methodsWe describe the 6-month multi-disciplinary planning phase to initiate an MRI-based brachytherapy program. We describe the specific challenges that were encountered prior to treating our first patient.ResultsWe describe the solutions that were realized and executed to solve the challenges that we faced to establish our MRI-based brachytherapy program. We emphasize detailed coordination of care, planning, and communication to make the workflow feasible. We detail the imaging and radiation physics solutions to safely deliver MRI-based brachytherapy. The focus of these efforts is always on the delivery of optimal, state of the art patient care and treatment delivery within the context of our available institutional resources.ConclusionsPrevious publications have supported a transition to MRI-based brachytherapy, and this can be safely and efficiently accomplished as described in this manuscript.

Dosimetric impact of interobserver variability in MRI-based delineation for cervical cancer brachytherapy

Purpose and backgroundTo study the dosimetric impact of interobserver delineation variability (IODV) in MRI-based cervical cancer brachytherapy. Materials and methodsMR images of six patients were distributed to 10 experienced observers worldwide. They were asked to delineate the target volumes and the organs at risk (OARs) for each patient. Two types of reference contours were created (Expert Consensus – EC and Simultaneous Truth and Performance Level Estimation – STAPLE). Optimised plans based on both EC- and STAPLE-contours were prepared. These plans were transferred to each of the observer contour sets and the resulting DVH parameters (D90 and D2cc) were calculated. For each patient the standard deviation (SD) for the 10 observers was calculated. ResultsA mean relative SD of 8–10% was found for GTV and High Risk CTV (HR-CTV) D90 analysing one single fraction. For rectum and bladder the mean relative SD for D2cc was 5–8% while sigmoid was at 11%. For the whole treatment the IODV in HR-CTV caused an uncertainty of ±5Gyα/β=10 (1SD). The corresponding figure for OARs was ±2–3Gyα/β=3. The results were not sensitive as to which structure set was used for the optimisation. ConclusionsFor the target volumes the dosimetric impact of IODV was smallest for the GTV and HR-CTV, while IODV had an even smaller impact on the bladder and rectum.

Applicator reconstruction in MRI 3D image-based dose planning of brachytherapy for cervical cancer

Background and purpose To elaborate a method for applicator reconstruction for MRI-based brachytherapy for cervical cancer. Materials and methods Custom-made plastic catheters with a copper sulphate solution were made for insertion in the source channels of MR-CT compatible applicators: plastic and titanium tandem ring applicators, and titanium needles. The applicators were CT and MR scanned in a phantom for accurate 3D assessment of applicator visibility and geometry. A reconstruction method was developed and evaluated in 19 patient MR examinations with ring applicator (plastic: 14, titanium: 5). MR applicator reconstruction uncertainties related to inter-observer variation were evaluated. Results The catheters were visible in the plastic applicator on T1-weighted images in phantom and in 14/14 clinical applications. On T2-weighted images, the catheters appeared weaker but still visible in phantom and in 13/14 MR clinical applications. In the titanium applicator, the catheters could not be separated from the artifacts from the applicator itself. However, these artifacts could be used to localize both titanium ring applicator (5/5 clinical applications) and needles (6/6 clinical applications). Standard deviations of inter-observer differences were below 2 mm in all directions. Conclusion 3D applicator reconstruction based on MR imaging could be performed for plastic and titanium applicators. Plastic applicators proved well to be suited for MRI-based reconstruction. For improved practicability of titanium applicator reconstruction, development of MR applicator markers is essential. Reconstruction of titanium applicator and needles at 1.5 T MR requires geometric evaluations in phantoms before using the applicator in patients.

3D MRI-based brachytherapy for cervical cancer

Brachytherapy (BT) represents an essential aspect of radical radiotherapy of cervical cancer. Within the last decade, 3D MRI-based BT was introduced into clinical practice at some institutions and it was shown that this advanced approach could successfully replace the traditional 2D x-ray-based methods of treatment planning. MRI has general advantages in the depiction of soft tissue and, in particular, in discrimination of cervical cancer from normal uterine and adjacent tissue. Accurate representation of pelvic anatomy and topography, together with detailed information regarding tumor extent and regression during the course of treatment, makes MRI essential for cervical cancer radiotherapy, particularly for BT. The process of implementation of 3D MRI-based BT is described in detail. The first reported single institutional retrospective analysis with systematic utilization of this novel treatment approach in a large consecutive patient series (n = 145) demonstrated the increase in local tumor control up t...

Applicator reconstruction in MRI 3D image-based dose planning of brachytherapy for cervical cancer

0167-8140/$ see front matter 2008 Elsevier Irelan doi:10.1016/j.radonc.2008.09.002 * Corresponding author. Address: Department of Bio University Hospital, Brendstrupgaardsvej, DK-8200 A E-mail address: sha@mta.aaa.dk (S. Haack). Background and purpose: To elaborate a method for applicator reconstruction for MRI-based brachytherapy for cervical cancer. Materials and methods: Custom-made plastic catheters with a copper sulphate solution were made for insertion in the source channels of MR-CT compatible applicators: plastic and titanium tandem ring applicators, and titanium needles. The applicators were CT and MR scanned in a phantom for accurate 3D assessment of applicator visibility and geometry. A reconstruction method was developed and evaluated in 19 patient MR examinations with ring applicator (plastic: 14, titanium: 5). MR applicator reconstruction uncertainties related to inter-observer variation were evaluated. Results: The catheters were visible in the plastic applicator on T1-weighted images in phantom and in 14/ 14 clinical applications. On T2-weighted images, the catheters appeared weaker but still visible in phantom and in 13/14 MR clinical applications. In the titanium applicator, the catheters could not be separated from the artifacts from the applicator itself. However, these artifacts could be used to localize both titanium ring applicator (5/5 clinical applications) and needles (6/6 clinical applications). Standard deviations of inter-observer differences were below 2 mm in all directions. Conclusion: 3D applicator reconstruction based on MR imaging could be performed for plastic and titanium applicators. Plastic applicators proved well to be suited for MRI-based reconstruction. For improved practicability of titanium applicator reconstruction, development of MR applicator markers is essential. Reconstruction of titanium applicator and needles at 1.5 T MR requires geometric evaluations in phantoms before using the applicator in patients. 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 91 (2009) 187–193

Dose volume relations in HR-CTV as predictive factors for local tumor control in MRI-based cervical cancer brachytherapy: Comparison between patients with and without recurrence

Purpose: The aim of this evaluation was to investigate dose-volume effect relationships in the CTV in MRI-based cervical cancer brachytherapy (BT) in order to obtain predictive factors for outcome. DVH-parameters from recurrent patients were compared to those of two other groups, both being representative for locally controlled disease, but differing in terms of technique and response.

22 Dose-volume-effect relations and pattern of response in MRI-based cervical cancer brachytherapy — Comparison between recurred and disease free patients

22 Dose-volume-effect relations and pattern of response in MRI-based cervical cancer brachytherapy — Comparison between recurred and disease free patients