BackgroundSegmentation of the Gross Tumor Volume (GTV) is a crucial step in the brachytherapy (BT) treatment planning workflow. Currently, radiation oncologists segment the GTV manually, which is... Show moreBackgroundSegmentation of the Gross Tumor Volume (GTV) is a crucial step in the brachytherapy (BT) treatment planning workflow. Currently, radiation oncologists segment the GTV manually, which is time-consuming. The time pressure is particularly critical for BT because during the segmentation process the patient waits immobilized in bed with the applicator in place. Automatic segmentation algorithms can potentially reduce both the clinical workload and the patient burden. Although deep learning based automatic segmentation algorithms have been extensively developed for organs at risk, automatic segmentation of the targets is less common. The aim of this study was to automatically segment the cervical cancer GTV on BT MRI images using a state-of-the-art automatic segmentation framework and assess its performance.MethodsA cohort of 195 cervical cancer patients treated between August 2012 and December 2021 was retrospectively collected. A total of 524 separate BT fractions were included and the axial T2-weighted (T2w) MRI sequence was used for this project. The 3D nnU-Net was used as the automatic segmentation framework. The automatic segmentations were compared with the manual segmentations used for clinical practice with Sørensen–Dice coefficient (Dice), 95th Hausdorff distance (95th HD) and mean surface distance (MSD). The dosimetric impact was defined as the difference in D98 (ΔD98) and D90 (ΔD90) between the manual segmentations and the automatic segmentations, evaluated using the clinical dose distribution. The performance of the network was also compared separately depending on FIGO stage and on GTV volume.ResultsThe network achieved a median Dice of 0.73 (interquartile range (IQR) = 0.50–0.80), median 95th HD of 6.8 mm (IQR = 4.2–12.5 mm) and median MSD of 1.4 mm (IQR = 0.90–2.8 mm). The median ΔD90 and ΔD98 were 0.18 Gy (IQR = -1.38–1.19 Gy) and 0.20 Gy (IQR =-1.10–0.95 Gy) respectively. No significant differences in geometric or dosimetric performance were observed between tumors with different FIGO stages, however significantly improved Dice and dosimetric performance was found for larger tumors.ConclusionsThe nnU-Net framework achieved state-of-the-art performance in the segmentation of the cervical cancer GTV on BT MRI images. Reasonable median performance was achieved geometrically and dosimetrically but with high variability among patients. Show less
Suvaal, I.; Kirchheiner, K.; Nout, R.A.; Sturdza, A.E.; Limbergen, E. van; Lindegaard, J.C.; ... ; Kuile, M.M. ter 2023
Objective. The EMBRACE-vaginal morbidity substudy prospectively evaluated physician-assessed vaginal changes and patient-reported-outcomes (PRO) on vaginal and sexual functioning problems and... Show moreObjective. The EMBRACE-vaginal morbidity substudy prospectively evaluated physician-assessed vaginal changes and patient-reported-outcomes (PRO) on vaginal and sexual functioning problems and distress in the first 2-years after image-guided radio(chemo)therapy and brachytherapy for locally advanced cervical cancer.Methods. Eligible patients had stage IB1-IIIB cervical cancer with <= 5 mm vaginal involvement. Assessment of vaginal changes was graded using CTCAE. PRO were assessed using validated Quality-of-Life and sexual question-naires. Statistical analysis included Generalized-Linear-Mixed-Models and Spearman's rho-correlation coeffi-cients.Results. 113 eligible patients were included. Mostly mild (grade 1) vaginal changes were reported over time in about 20% (range 11-37%). At 2-years, 47% was not sexually active. Approximately 50% of the sexually active women reported any vaginal and sexual functioning problems and distress over time; more substantial vaginal and sexual problems and distress were reported by up to 14%, 20% and 8%, respectively. Physician-assessed vag-inal changes and PRO sexual satisfaction differed significantly (p <=.05) between baseline and first follow-up, without further significant changes over time. No or only small associations between physician-assessed vaginal changes and PRO vaginal functioning problems and sexual distress were found.Conclusions. Mild vaginal changes were reported after image-guided radio(chemo)therapy and brachyther-apy, potentially due to the combination of tumors with limited vaginal involvement, EMBRACE-specific treatment optimization and rehabilitation recommendations. Although vaginal and sexual functioning problems and sexual distress were frequently reported, the rate of substantial problems and distress was low. The lack of association between vaginal changes, vaginal functioning problems and sexual distress shows that sexual functioning is more complex than vaginal morbidity alone.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Endometrial cancer (EC) is the most common gynaecological cancer in developed countries. Standard treatment consists of surgery (hysterectomy and bilateral salpingo-oophorectomy) followed by either... Show moreEndometrial cancer (EC) is the most common gynaecological cancer in developed countries. Standard treatment consists of surgery (hysterectomy and bilateral salpingo-oophorectomy) followed by either no adjuvant treatment, vaginal brachytherapy (VBT) or external beam radiotherapy (EBRT) with or without chemotherapy. The type of adjuvant treatment is based on clinicopathologic risk factors as age, FIGO-stage, histologic type and grade, myometrial invasion and lymph-vascular space invasion. In the recent years, knowledge has been gained on molecular risk factors in EC and four different molecular subgroups with distinct prognosis have been defined. The implementation of these subgroups into the treatment guidelines is being investigated in the PORTEC-4a trial. In this trial women with high-intermediate risk EC are randomised to either VBT versus an experimental arm in which a molecular-integrated risk profile is used to guide adjuvant treatment. With the improved patient selection women with favourable prognosis can be spared unnecessary treatment, while those with unfavourable prognosis are treated with more intensive treatment (EBRT). Besides the improvement of patient selection, radiotherapy techniques have developed as well. Modern radiotherapy techniques can increasingly spare healthy tissues with comparable outcomes and less toxicity. These developments will lead to better results and higher(er) quality-of-life for women with EC. Show less
This thesis describes the use of high-dose-rate endorectal brachytherapy as a boost to external beam radiotherapy in patients with rectal cancer. With 60% clinical complete response in the HERBERT... Show moreThis thesis describes the use of high-dose-rate endorectal brachytherapy as a boost to external beam radiotherapy in patients with rectal cancer. With 60% clinical complete response in the HERBERT study, this treatment is very promising for use in organ preservation studies. Both toxicity of external beam radiotherapy as toxicity of brachytherapy are addressed and further improvements to the brachytherapy technique are suggested to increase tumor control while limiting toxicity. Show less
Background and purpose: A matched comparison of external beam radiotherapy (EBRT) versus brachytherapy recently demonstrated that EBRT appears at least as effective for palliating dysphagia in... Show moreBackground and purpose: A matched comparison of external beam radiotherapy (EBRT) versus brachytherapy recently demonstrated that EBRT appears at least as effective for palliating dysphagia in patients with incurable esophageal cancer. The aim of this analysis was to compare patient-reported outcomes (PROs) after EBRT versus brachytherapy.Materials and methods: In a multicenter prospective cohort study, patients with incurable esophageal cancer requiring palliation of dysphagia were included to undergo EBRT (20 Gy in 5 fractions). This EBRT cohort was compared to the single-dose 12 Gy brachytherapy cohort of the previously reported SIRECtrial. Propensity score matching was applied to adjust for baseline imbalances. The primary endpoint of dysphagia improvement was reported previously. PROs were secondary outcomes and assessed at baseline and 3 months after treatment using EORTC QLQ-C30 and QLQ-OES18 questionnaires.Results: A total of 115 enrolled EBRT patients and 93 brachytherapy patients were eligible. After matching, 69 well-balanced pairs remained. At follow-up, significant deteriorations in functioning (i.e. physical, role, social), pain, appetite loss, and trouble with taste were observed after brachytherapy. In the EBRT group, such deterioration was observed only for role functioning, while significant improvements in trouble with eating and pain were found. Between-group comparison showed mostly comparable PRO changes, but significantly favored EBRT with regard to nausea, vomiting, pain, and appetite loss.Conclusion: Short course EBRT results in similar or better PROs at 3 months after treatment compared to single-dose brachytherapy for the palliation of malignant dysphagia. These findings further support its use and inclusion in clinical practice guidelines. (C) 2020 The Author(s). Published by Elsevier B.V. Show less
Improvements in the treatment of rectal cancer patients have led to increased survival. Therefore, long-term outcome has become an increasingly important factor. Both neoadjuvant (chemo... Show moreImprovements in the treatment of rectal cancer patients have led to increased survival. Therefore, long-term outcome has become an increasingly important factor. Both neoadjuvant (chemo)radiotherapy and total mesorectal excision surgery are associated with toxicity. As a result, research for rectal cancer treatment has focused on the reduction of radiation dose to healthy tissue and less extensive surgery or omission of surgery in selected patients. The work described in this thesis can be used to reduce uncertainties related to image-guided external beam radiotherapy (EBRT) and high-dose-rate endorectal brachytherapy (HDREBT) of rectal cancer. By decreasing treatment related uncertainties, dose to surrounding healthy tissue can be reduced and/or a higher dose to the target volume can be delivered with an isotoxic effect. The MRI visibility of four types of fiducial markers as a surrogate for gross tumor volume (GTV) location was evaluated. In addition, it was found that the use of fiducial markers as a surrogate for GTV location in an EBRT GTV boost setting allows smaller treatment margins. For HDREBT, it was found that daily CT imaging should be the minimal standard to verify a correct applicator setup. In addition, we propose the use of an ultrashort echo time MRI sequence to visualize the applicator on MRI. Lastly, we determined the added value of a national study group meeting on the quality and variability of EBRT treatment plans for the introduction of a novel target volume that includes only the mesorectum. Show less
Ende, R.P.J. van den; Ercan, E.; Keesman, R.; Kerkhof, E.M.; Marijnen, C.A.M.; Heide, U.A. van der 2020
PURPOSE: The individual channels in an endorectal applicator for high-dose-rate endorectal brachytherapy are not visible on standard MRI sequences. The aim of this study was to test whether an... Show morePURPOSE: The individual channels in an endorectal applicator for high-dose-rate endorectal brachytherapy are not visible on standard MRI sequences. The aim of this study was to test whether an ultrashort echo time (UTE) MRI sequence could be used to visualize the individual channels to enable MR-only treatment planning for rectal cancer.METHODS AND MATERIALS: We used a radial three-dimensional (3D) UTE pulse sequence and acquired images of phantoms and two patients with rectal cancer. We rigidly registered a UTE image and CT scan of an applicator phantom, based on the outline of the applicator. One observer compared channel positions on the UTE image and CT scan in five slices spaced 25 mm apart. To quantify geometric distortions, we scanned a commercial 3D geometric quality assurance phantom and calculated the difference between detected marker positions on the UTE image and corresponding marker positions on two 3D T-1-weighted images with opposing readout directions.RESULTS: On the UTE images, there is sufficient contrast to discern the individual channels. The difference in channel positions on the UTE image compared with the CT was on average -0.1 +/- 0.1 mm (left-right) and 0.1 +/- 0.3 mm (anteroposterior). After rigid registration to the 3D T-1-weighted sequences, the residual 95th percentile of the geometric distortion inside a 550-mm-diameter sphere was 1.0 mm (left-right), 0.9 mm (anteroposterior), and 0.9 mm (craniocaudal).CONCLUSIONS: With a UTE sequence, the endorectal applicator and individual channels can be adequately visualized in both phantom and patients. The geometrical fidelity is within an acceptable range. (C) 2020 The Authors. Published by Elsevier Inc. on behalf of American Brachytherapy Society. Show less
Introduction: Short-course external beam radiotherapy (EBRT) and intraluminal brachytherapy are both accepted treatments for the palliation of dysphagia in patients with incurable esophageal cancer... Show moreIntroduction: Short-course external beam radiotherapy (EBRT) and intraluminal brachytherapy are both accepted treatments for the palliation of dysphagia in patients with incurable esophageal cancer. We compared the effects of both treatments from two prospective studies.Methods: We performed a multicenter prospective cohort study of patients with metastasized or otherwise incurable esophageal cancer requiring palliation of dysphagia from September 2016 to March 2019. Patients were treated with EBRT in five fractions of 4 Gy. Data were compared with all patients treated with a single brachytherapy dose of 12 Gy in the SIREC (Stent or Intraluminal Radiotherapy for inoperable Esophageal Cancer) trial, both between the original cohorts and between 1:1 propensity score-matched cohorts. The primary end point was an improvement of dysphagia at 3 months without reintervention. The secondary end points included toxicity and time-to-effect.Results: A total of 115 patients treated with EBRT and 93 patients who underwent brachytherapy were eligible for analysis. In the original cohorts, dysphagia improved after EBRT in 79% of patients compared with 64% after brachytherapy (p = 0.058). Propensity score matching resulted in 69 patients in each cohort well-balanced at baseline. Improvement of dysphagia was observed in 83% after EBRT versus 64% after brachytherapy (p = 0.048). In responding patients, improvement of dysphagia at 2 weeks was observed in 67% after EBRT compared with 35% after brachytherapy, and the maximum effect was reached after 4 weeks in 55% and 33%, respectively. Severe toxicity occurred in 3% of patients after EBRT compared with 13% after brachytherapy.Conclusions: Short-course EBRT appears at least as effective as brachytherapy in the palliation of dysphagia in patients with esophageal cancer. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. Show less
Rijkmans, E.C.; Marijnen, C.A.M.; Triest, B. van; Ketelaars, M.; Cats, A.; Inderson, A.; ... ; Nout, R.A. 2019
PURPOSE: Structure-based deformable image registration (DIR) can be used to calculate accumulated dose volume histogram parameters for cervical cancer brachytherapy (BT). The purpose of this study... Show morePURPOSE: Structure-based deformable image registration (DIR) can be used to calculate accumulated dose volume histogram parameters for cervical cancer brachytherapy (BT). The purpose of this study is to investigate dose warping uncertainties for the accumulated dose to the 2 cm(3) receiving the highest dose (D-2 cm(3)) in the rectal wall, using a physically realistic model (PRM) describing rectal wall deformation.METHODS AND MATERIALS: For 10 patients, treated with MRI-guided pulsed dose rate BT (two times 24 x 0.75 Gy, given in two applications BT1 and BT2), the planning images were registered with structure-based DIR. The resulting transformation vectors were used to accumulate the total rectum dose from BT. To investigate the dose warping uncertainty, a PRM describing rectal deformation was used. For point pairs on rectum(BTl) and rectum(BT2) that were at the same location according to the PRM, the dose for BT1 and BT2 was added (D-PRM) and compared to the DIR-accumulated dose (D-DIR) in the BT2 point. The remaining distance after DIR between corresponding point pairs, defined as the residual distance, was calculated.RESULTS: For points within the D-2 cm(3) volume, more than 75% was part of the D-2 cm(3) volume according to both PRM and DIR. The absolute dose difference was <7.3 Gy(EQD2), and the median (95th percentile) of the residual distance was 8.7 (22) mm.CONCLUSIONS: DIR corresponded with the PRM for on average 75% of the D-2 cm(3) volume. Local absolute dose differences and residual distances were large. Care should therefore be taken with DIR for dose-warping purposes in BT. (C) 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. Show less
Ende, R.P.J. van den; Rijkmans, E.C.; Kerkhof, E.M.; Nout, R.A.; Ketelaars, M.; Laman, M.S.; ... ; Heide, U.A. van der 2018
Background and purpose: Structure -based deformable image registration (DIR) can be used to calculate accumulated brachytherapy (BT) and external -beam radiation therapy (EBRT) dose-volume... Show moreBackground and purpose: Structure -based deformable image registration (DIR) can be used to calculate accumulated brachytherapy (BT) and external -beam radiation therapy (EBRT) dose-volume histogram (DVH) parameters in cervical cancer. Since direct parameter addition does not take dose non uniformity into account, the added value of DIR over addition methods was investigated for bladder and rectum.Materials and methods: For twelve patients (EBRT: 46 Gy, EBRT + BT: D-90 85-90 Gy(EQD2) in equivalent dose in 2 Gy fractions) the EBRT planning CT and BT planning MRI were registered using DIR. Affected lymph nodes, located far from the BT boost region, received an EBRT boost (9.2 Gy) not contributing to the BT boost dose. Cumulative bladder/rectum D-2cm3/D-1cm3 were calculated and compared to direct addition methods, assuming uniform EBRT doses (UD), or overlapping high dose volumes (OHD).Results: Between the three methods, the maximum differences in the cumulative DVH parameters were 3.2 GY(EQD2) (bladder) and 3.3 GY(EQD2) (rectum). The difference between DIR and UD was <1.8 GY(EQD2) for both organs.Conclusions: The UD method provides a better estimate of D2cm3/D1cm3 than the OHD method. There is no added value of DIR since differences with direct addition methods are clinically insignificant. EBRT dose distributions can be considered uniform in bladder and rectum for the evaluated dose parameters. (C) 2017 Elsevier B.V. All rights reserved. Show less
Marinkovic, M.; Horeweg, N.; Fiocco, M.; Peters, F.P.; Sommers, L.W.; Laman, M.S.; ... ; Creutzberg, C.L. 2016
PURPOSE: To quantify distortions on MR images of the Utrecht interstitial CT/MR applicator at a field strength of 3T using an MRI-only method.MATERIALS AND METHODS: An MR-compatible phantom... Show morePURPOSE: To quantify distortions on MR images of the Utrecht interstitial CT/MR applicator at a field strength of 3T using an MRI-only method.MATERIALS AND METHODS: An MR-compatible phantom suspending the applicator in water was built and imaged on a Philips Ingenia 3T MRI scanner. A map of the magnetic field (B-0) was calculated from multiecho images and used to quantify the field inhomogeneity. The expected displacements of the applicator could be quantified using the measured field inhomogeneity and sequence bandwidth. Additionally, two scans were acquired using opposing readout gradients. These scans were rigidly matched and their displacement was compared with the expected displacements from the B-0 map.These same methods were applied in 4 patients. By rigid matching of the scans acquired with opposing readout direction the applicator displacement due to image distortion from B-0 inhomogeneity as well as patient movement and organ deformation was determined.RESULTS: According to the B-0 map, the displacement on the intrauterine device of the plastic brachytherapy applicator was <0.4 mm for both the phantom and patients. Displacements obtained by the opposing readout method were <= 0.8 mm for each patient with a mean +/- SD over the patients of 0.3 +/- 0.1 mm.CONCLUSION: The results of our study indicate that the B-0 method agrees with the opposing readout method. Displacements caused by magnetic field inhomogeneity on 3T MRI were small compared with displacements due to patient movement and organ deformation. (C) 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. Show less
Objective. The aim of this study is to investigate the impact of treatment policy changes in cervical cancer patients treated with adjuvant (chemo) radiotherapy.Methods. Between 1970 and 2007, 292... Show moreObjective. The aim of this study is to investigate the impact of treatment policy changes in cervical cancer patients treated with adjuvant (chemo) radiotherapy.Methods. Between 1970 and 2007, 292 patients received adjuvant radiotherapy after a radical hysterectomy with pelvic lymphadenectomy for early stage cervical carcinoma. All patients received pelvic radiotherapy (40 Gy-46 Gy in 1.8 Gy-2 Gy/fraction). Vaginal vault brachytherapy boost (10-14 Gy) was increasingly used for patients with high-risk factors, and since 1993 systematically applied in patients with at least 2 of the 3 risk factors: adenocarcinoma, nodal involvement and parametrial invasion. Cisplatin-based chemotherapy was introduced in this group of patients from 2000.Results. The 5-year cumulative risk of local recurrence (CRLR) was 13% (95%CI 9%-17%), resulting in an overall 5-year survival (OS) of 78% (95%CI 83%-73%). Since 1970, the OR for the 5-year locoregional recurrence risk (LRR) decreased from 2.5 to 1.15 (linear-OR = -0.02/year). The OR for the 5-year mortality risk reduced from 2.2 in 1970 to 1.0 in 2007 (linear-OR = -0.03/year). The largest risk reductions were observed before 1990 with a minor rise after 2002. The risk of severe late toxicity reduced from 1.8% to 1.5% (linear-OR = -0.03/year). The addition of concomitant adjuvant chemotherapy since 2000 may have benefited a subgroup of patients with squamous cell carcinoma, but not the patients with adenocarcinoma, and after introduction of chemotherapy the risk of severe late toxicity tripled from 2% to 7%.Conclusion. Since 1970, tumour recurrence risk and mortality have decreased, as radiation dose increased. The potential benefit of concomitant adjuvant chemotherapy could not be demonstrated in this nonrandomized study. (C) 2014 Elsevier Inc. All rights reserved. Show less
