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
Ghuijs, W.; Kemps, P.G.; Capala, M.E.; Verdijk, R.M.; Halteren, A.G.S. van; Wal, R.J.P. van der; Laar, J.A.M. van 2022
Background Langerhans cell histiocytosis (LCH) is a rare haematological neoplasm characterized by the accumulation of CD1a(+), CD207/Langerin(+) histiocytes within inflammatory lesions. LCH can... Show moreBackground Langerhans cell histiocytosis (LCH) is a rare haematological neoplasm characterized by the accumulation of CD1a(+), CD207/Langerin(+) histiocytes within inflammatory lesions. LCH can involve any organ, but osteolytic bone lesions are most often encountered. Unifocal bone lesions may regress spontaneously after a thick needle biopsy has been taken. Case presentation In this case report, we describe the initial presentation of a single BRAF(V600E) mutated osteolytic LCH lesion in the left proximal humerus of a 46-year-old previously healthy woman. Despite multiple surgical interventions, she unexpectedly experienced progressive disease manifestation with significant soft tissue extension to the surrounding musculature, subcutis and epidermis. Because the disease manifestation remained loco-regional, radiotherapy (RT) (total dose of 20 Gy in 10 fractions) was initiated. Conclusion The patient achieved a complete remission without any side effects. This case highlights that RT is a rational and relative mild local treatment option for patients with aggressive LCH affecting the bone and surrounding soft tissue. Show less
Kensen, C.M.; Janssen, T.M.; Betgen, A.; Wiersema, L.; Peters, F.P.; Remeijer, P.; ... ; Heide, U.A. van der 2022
Purpose: To determine PTV margins for intrafraction motion in MRI-guided online adaptive radiotherapy for rectal cancer and the potential benefit of performing a 2nd adaptation prior to irradiation... Show morePurpose: To determine PTV margins for intrafraction motion in MRI-guided online adaptive radiotherapy for rectal cancer and the potential benefit of performing a 2nd adaptation prior to irradiation. Methods: Thirty patients with rectal cancer received radiotherapy on a 1.5 T MR-Linac. On T2-weighted images for adaptation (MRIadapt), verification prior to (MRIver) and after irradiation (MRIpost) of 5 treatment fractions per patient, the primary tumor GTV (GTV(prim)) and mesorectum CTV (CTVmeso) were delineated. The structures on MRIadapt were expanded to corresponding PTVs. We determined the required expansion margins such that on average over 5 fractions, 98% of CTVmeso and 95% of GTV(prim) on MRIpost was covered in 90% of the patients. Furthermore, we studied the benefit of an additional adaptation, just prior to irradiation, by evaluating the coverage between the structures on MRIver and MRIpost. A threshold to assess the need for a secondary adaptation was determined by considering the overlap between MRIadapt and MRIver. Results: PTV margins for intrafraction motion without 2nd adaptation were 6.4 mm in the anterior direction and 4.0 mm in all other directions for CTVmeso and 5.0 mm isotropically for GTV(prim). A 2nd adaptation, applied for all fractions where the motion between MRIadapt and MRIver exceeded 1 mm (36% of the fractions) would result in a reduction of the PTVmeso margin to 3.2 mm/2.0 mm. For PTVprim a margin reduction to 3.5 mm is feasible when a 2nd adaptation is performed in fractions where the motion exceeded 4 mm (17% of the fractions). Conclusion: We studied the potential benefit of intrafraction motion monitoring and a 2nd adaptation to reduce PTV margins in online adaptive MRIgRT in rectal cancer. Performing 2nd adaptations immediately after online replanning when motion exceeded 1 mm and 4 mm for CTVmeso and GTV(prim) respectively, could result in a 30-50% margin reduction with limited reduction of dose to the bowel. Show less
Neelis, K.J.; Kip, D.M.; Speetjens, F.M.; Linden, Y.M. van der 2022
Background and purpose To gain insight into the treatment outcomes for anal cancer a retrospective analysis was performed with a special emphasis on trends in outcome and toxicities over time and... Show moreBackground and purpose To gain insight into the treatment outcomes for anal cancer a retrospective analysis was performed with a special emphasis on trends in outcome and toxicities over time and on treatment of elderly patients. Materials and methods Medical records of 98 consecutive patients with squamous cell carcinoma of the anus of all stages treated with curative intent between 01-01-2009 and 31-12-2018 were analyzed with follow up until 31-12-2020. Standard tumor and pathological lymph node dose were 59.4 Gy (median 59.4 Gy, range 59.4-70 Gy) or 60 Gy (no deviation from intended dose), elective nodal regions were treated with 45 Gy (no deviations). Radiotherapy techniques in this period evolved from 3D-conformal to IMRT and VMAT. In 23 patients electron beams were used. Results Median age was 63 years (range 41-88), the majority of patients were female (60%). Twenty three patients were > 75 years old. The TNM stages were I, II, IIIA, and IIIB in 18%, 40%, 15% and 27%, 58% of patients had N0 status. Concurrent mitomycin C and 5-fluoruracil-based chemotherapy was given in 63 patients (64%). Five-year overall survival (OS), disease free survival (DFS), locoregional control (LRC) and colostomy free survival (CFS) were 71%, 80%, 82%, and 82% for the whole group. Results in patients > 75 years of age were not statistically different from those in younger patients. With the introduction of more conformal techniques DFS did not change and toxicities decreased. Conclusion Real word treatment outcomes per disease stage were in line with what is reported in literature. Older patients should also be offered treatment with curative intent. Show less
Background Radiotherapy (RT) is part of the curative treatment of approximately 70% of breast cancer (BC) patients. Wide practice variation has been reported in RT dose, fractionation and its... Show moreBackground Radiotherapy (RT) is part of the curative treatment of approximately 70% of breast cancer (BC) patients. Wide practice variation has been reported in RT dose, fractionation and its treatment planning for BC. To decrease this practice variation, it is essential to first gain insight into the current variation in RT treatment between institutes. This paper describes the development of the NABON Breast Cancer Audit-Radiotherapy (NBCA-R), a structural nationwide registry of BC RT data of all BC patients treated with at least surgery and RT. Methods A working group consisting of representatives of the BC Platform of the Dutch Radiotherapy Society selected a set of dose volume parameters deemed to be surrogate outcome parameters, both for tumour control and toxicity. Two pilot studies were carried out in six RT institutes. In the first pilot study, data were manually entered into a secured web-based system. In the second pilot study, an automatic Digital Imaging and Communications in Medicine (DICOM) RT upload module was created and tested. Results The NBCA-R dataset was created by selecting RT parameters describing given dose, target volumes, coverage and homogeneity, and dose to organs at risk (OAR). Entering the data was made mandatory for all Dutch RT departments. In the first pilot study (N = 1093), quite some variation was already detected. Application of partial breast irradiation varied from 0 to 17% between the 6 institutes and boost to the tumour bed from 26.5 to 70.2%. For patients treated to the left breast or chest wall only, the average mean heart dose (MHD) varied from 0.80 to 1.82 Gy; for patients treated to the breast/chest wall only, the average mean lung dose (MLD) varied from 2.06 to 3.3 Gy. In the second pilot study 6 departments implemented the DICOM-RT upload module in daily practice. Anonymised data will be available for researchers via a FAIR (Findable, Accessible, Interoperable, Reusable) framework. Conclusions We have developed a set of RT parameters and implemented registration for all Dutch BC patients. With the use of an automated upload module registration burden will be minimized. Based on the data in the NBCA-R analyses of the practice variation will be done, with the ultimate aim to improve quality of BC RT. Trial registration Retrospectively registered. Show less
Ende, R.P.J. van den; Peters, F.P.; Harderwijk, E.; Rutten, H.; Bouwmans, L.; Berbee, M.; ... ; Kerkhof, E.M. 2020
Background The STAR-TReC trial is an international multi-center, randomized, phase II study assessing the feasibility of short-course radiotherapy or long-course chemoradiotherapy as an alternative... Show moreBackground The STAR-TReC trial is an international multi-center, randomized, phase II study assessing the feasibility of short-course radiotherapy or long-course chemoradiotherapy as an alternative to total mesorectal excision surgery. A new target volume is used for both (chemo)radiotherapy arms which includes only the mesorectum. The treatment planning QA revealed substantial variation in dose to organs at risk (OAR) between centers. Therefore, the aim of this study was to determine the treatment plan variability in terms of dose to OAR and assess the effect of a national study group meeting on the quality and variability of treatment plans for mesorectum-only planning for rectal cancer. Methods Eight centers produced 25 x 2 Gy treatment plans for five cases. The OAR were the bowel cavity, bladder and femoral heads. A study group meeting for the participating centers was organized to discuss the planning results. At the meeting, the values of the treatment plan DVH parameters were distributed among centers so that results could be compared. Subsequently, the centers were invited to perform replanning if they considered this to be necessary. Results All treatment plans, both initial planning and replanning, fulfilled the target constraints. Dose to OAR varied considerably for the initial planning, especially for dose levels below 20 Gy, indicating that there was room for trade-offs between the defined OAR. Five centers performed replanning for all cases. One center did not perform replanning at all and two centers performed replanning on two and three cases, respectively. On average, replanning reduced the bowel cavity V20Gy by 12.6%, bowel cavity V10Gy by 22.0%, bladder V35Gy by 14.7% and bladder V10Gy by 10.8%. In 26/30 replanned cases the V10Gy of both the bowel cavity and bladder was lower, indicating an overall lower dose to these OAR instead of a different trade-off. In addition, the bowel cavity V10Gy and V20Gy showed more similarity between centers. Conclusions Dose to OAR varied considerably between centers, especially for dose levels below 20 Gy. The study group meeting and the distribution of the initial planning results among centers resulted in lower dose to the defined OAR and reduced variability between centers after replanning. Show less
Visser, J.; Boer, P. de; Crama, K.F.; Kesteren, Z. van; Rasch, C.R.N.; Stalpers, L.J.A.; Bel, A. 2019
BackgroundOnline magnetic resonance imaging (MRI)-guided radiotherapy of cervical cancer has the potential to further reduce dose to organs at risk (OAR) as compared to a library of plans (LOP)... Show moreBackgroundOnline magnetic resonance imaging (MRI)-guided radiotherapy of cervical cancer has the potential to further reduce dose to organs at risk (OAR) as compared to a library of plans (LOP) approach. This study presents a dosimetric comparison of an MRI-guided strategy with a LOP strategy taking intrafraction anatomical changes into account.MethodsThe 14 patients included in this study were treated with chemo radiation at our institute and received weekly MRIs after informed consent. The MRI-guided strategy consisted of treatment plans created on the weekly sagittal MRI with 3mm and 5mm planning target volume (PTV) margin for clinical target volume (CTV) cervix-uterus (MRI_3mm and MRI_5mm). The plans for the LOP strategy were based on interpolations of CTV cervix-uterus on pretreatment full and empty bladder scans. Dose volume histogram (DVH) parameters were compared for targets and OARs as delineated on the weekly transversal MRI, which was acquired on average 10min after the sagittal MRI.ResultsFor the MRI_5mm strategy D-98% of the high-risk CTV was at least 95% for all weekly MRIs of all patients, while for the LOP and MRI_3mm strategy this requirement was not satisfied for at least one weekly MRI for 1 and 3 patients, respectively. The average reduction of the volume of the reference dose (95% of the prescribed dose) as compared to the LOP strategy was 464cm(3) for the MRI_3mm strategy, and 422cm(3) for the MRI_5mm strategy. The bowel bag constraint V-40Gy<350cm(3) was violated for 13 patients for the LOP strategy and for 5 patients for both MRI_3mm and MRI_5mm strategy.ConclusionsWith online MRI-guided radiotherapy of cervical cancer considerable sparing of OARs can be achieved. If a new treatment plan can be generated and delivered within 10min, an online MRI-guided strategy with a 5mm PTV margin for CTV cervix-uterus is sufficient to account for intrafraction anatomical changes.Trial registrationNL44492.018.13. Show less
Linge, A. van; Os, R. van; Hoekstra, N.; Heijmen, B.; Stienstra, L.; Dallenga, A.; ... ; Romero, A.M. 2018
BackgroundAlthough stereotactic radiotherapy (SRT) for vestibular schwannoma has demonstrated excellent local control rates, hearing deterioration is often reported after treatment. We therefore... Show moreBackgroundAlthough stereotactic radiotherapy (SRT) for vestibular schwannoma has demonstrated excellent local control rates, hearing deterioration is often reported after treatment. We therefore wished to assess the change in hearing loss after SRT and to determine which patient, tumor and treatment-related factors influence deterioration.MethodsWe retrospectively analyzed progression of hearing loss in patients with vestibular schwannoma who had received stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) as a primary treatment between 2000 and 2014. SRS had been delivered as a single fraction of 12Gy, and patients treated with FSRT had received 30 fractions of 1.8Gy. To compare the effects of SRS and FSRT, we converted cochlear doses into EQD(2). Primary outcomes were loss of functional hearing, Gardner Robertson (GR) classes I and II, and loss of baseline hearing class. These events were used in Kaplan Meier plots and Cox regression. We also calculated the rate of change in Pure Tone Average (PTA) in dB per month elapsed after radiationa measure we use in linear regressionto assess the associations between the rate of change in PTA and age, pre-treatment hearing level, tumor size, dose scheme, cochlear dose, and time elapsed after treatment (time-to-first-audiogram).ResultsThe median follow-up was 36months for 67 SRS patients and 63months for 27 FSRT patients. Multivariate Cox regression and in linear regression both showed that the cochlear V90 was significantly associated with the progression of hearing loss. But although pre-treatment PTA correlated with rate of change in Cox regression, it did not correlate in linear regression. The time-to-first-audiogram was also significantly associated, indicating time dependency of the rate of change. None of the analysis showed a significant difference between dose schemes.ConclusionsWe found no significant difference between SRS and FSRT. As the deterioration in hearing after radiotherapy for vestibular schwannoma was associated with the cochlea V90, restricting the V90 may reduce progression of hearing loss. The association between loss of functional hearing and baseline PTA seems to be biased by the use of a categorized variable for hearing loss. Show less
Background: In adults, a single pre-treatment four-dimensional CT (4D-CT) acquisition is often used to account for respiratory-induced target motion during radiotherapy. However, studies have... Show moreBackground: In adults, a single pre-treatment four-dimensional CT (4D-CT) acquisition is often used to account for respiratory-induced target motion during radiotherapy. However, studies have indicated that a 4D-CT is not always representative for respiratory motion. Our aim was to investigate whether respiratory-induced diaphragm motion in children on a single pre-treatment 4DCT can accurately predict respiratory-induced diaphragm motion as observed on cone beam CTs (CBCTs).Methods: Twelve patients (mean age 14.5 yrs.; range 8.6-17.9 yrs) were retrospectively included based on visibility of the diaphragm on abdominal or thoracic imaging data acquired during free breathing. A 4DCT for planning purposes and daily/weekly CBCTs (total 125; range 4-29 per patient) acquired prior to dose delivery were available. The amplitude, corresponding to the difference in position of the diaphragm in cranial-caudal direction in end-inspiration and end-expiration phases, was extracted from the 4DCT (A(4DCT)). The amplitude in CBCTs (A(CBCT)) was defined as displacement between averaged in- and expiration diaphragm positions on corresponding projection images, and the distribution of A(CBCT) was compared to A(4DCT) (one-sample t-test, significance level p<0.05).Results: Over all patients, the mean A(4DCT) was 10.4 mm and the mean A(CBCT) 11.6 mm. For 9/12 patients, A(4DCT) differed significantly (p<0.05) from A(CBCT). Differences >3 mm were found in 69/125 CBCTs (55%), with A(4DCT) mostly underestimating A(CBCT). For 7/12 patients, diaphragm positions differed significantly from the baseline position.Conclusion: Respiratory-induced diaphragm motion determined on 4DCT does not accurately predict the daily respiratory-induced diaphragm motion observed on CBCTs, as the amplitude and baseline position differed statistically significantly in the majority of patients. Regular monitoring of respiratory motion during the treatment course using CBCTs could yield a higher accuracy when a daily adaptation to the actual breathing amplitude takes place. Show less
Huijskens, S.C.; Dijk, I.W.E.M. van; Visser, J.; Balgobind, B.V.; Lindert, D. te; Rasch, C.R.N.; ... ; Bel, A. 2018
Background: Interfractional organ position variation might differ for abdominal organs and this could have consequences for defining safety margins. Therefore, the purpose of this study is to... Show moreBackground: Interfractional organ position variation might differ for abdominal organs and this could have consequences for defining safety margins. Therefore, the purpose of this study is to quantify interfractional position variations of abdominal organs in children in order to investigate possible correlations between abdominal organs and determine whether position variation is location-dependent.Methods: For 20 children (2.2-17.8 years), we retrospectively analyzed 113 CBCTs acquired during the treatment course, which were registered to the reference CT to assess interfractional position variation of the liver, spleen, kidneys, and both diaphragm domes. Organ position variation was assessed in three orthogonal directions and relative to the bony anatomy. Diaphragm dome position variation was assessed in the cranial-caudal (CC) direction only. We investigated possible correlations between position variations of the organs (Spearman's correlation test, p), and tested if organ position variations in the CC direction are related to the diaphragm dome position variations (linear regression analysis, R-2) (both tests: significance level p < 0.05). Differences of variations of systematic (Sigma) and random errors (sigma) between organs were tested (Bonferroni significance level p < 0.004).Results: In all directions, correlations between liver and spleen position variations, and between right and left kidney position variations were weak (p <= 0.43). In the CC direction, the position variations of the right and left diaphragm domes were significantly, and stronger, correlated with position variations of the liver (R-2 = 0.55) and spleen (R-2 = 0.63), respectively, compared to the right (R-2 = 0.00) and left kidney (R-2 = 0.25). Differences in Sigma and sigma between all organs were small and insignificant.Conclusions: No (strong) correlations between interfractional position variations of abdominal organs in children were observed. From present results, we concluded that diaphragm dome position variations could be more representative for superiorly located abdominal (liver, spleen) organ position variations than for inferiorly located (kidneys) organ position variations. Differences of systematic and random errors between abdominal organs were small, suggesting that for margin definitions, there was insufficient evidence of a dependence of organ position variation on anatomical location. Show less
Versteijne, E.; Gurney-Champion, O.J.; Horst, A. van der; Lens, E.; Kolff, M.W.; Buijsen, J.; ... ; Tienhoven, G. van 2017
Purpose: To determine the variation in target delineation of nasopharyngeal carcinoma and the impact of measures to minimize this variation.Materials and methods: For ten nasopharyngeal cancer... Show morePurpose: To determine the variation in target delineation of nasopharyngeal carcinoma and the impact of measures to minimize this variation.Materials and methods: For ten nasopharyngeal cancer patients, ten observers each delineated the Clinical Target Volume (CTV) and the CTV elective. After 3D analysis of the delineated volumes, a second delineation was performed. This implied improved delineation instructions, a combined delineation on CT and co-registered MRI, forced use of sagittal reconstructions, and an on-line anatomical atlas.Results: Both for the CTV and the CTV elective delineations, the 3D SD decreased from Phase 1 to Phase 2, from 4.4 to 3.3 mm for the CTV and from 5.9 to 4.9 mm for the elective. There was an increase agreement, where the observers intended to delineate the same structure, from 36 to 64 surface % (p = 0.003) for the CTV and from 17 to 59% (p = 0.004) for the elective. The largest variations were at the caudal border of the delineations but these were smaller when an observer utilized the sagittal window. Hence, the use of sagittal side windows was enforced in the second phase and resulted in a decreased standard deviation for this area from 7.7 to 3.3 mm (p = 0.001) for the CTV and 7.9 to 5.6 mm ( p = 0.03) for the CTV elective.Discussion: Attempts to decrease the variation need to be tailored to the specific causes of the variation. Use of delineation instructions multimodality imaging, the use of sagittal windows and an on-line atlas result in a higher agreement on the intended target. Show less
