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
Groen, V.H.; Schie, M. van; Zuithoff, N.P.A.; Monninkhof, E.M.; Kunze-Busch, M.; Boer, J.C.J. de; ... ; Kerkmeijer, L.G.W. 2022
Purpose or objectives: The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractionated EBRT in the treatment of localized prostate cancer, the five-year biochemical... Show morePurpose or objectives: The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractionated EBRT in the treatment of localized prostate cancer, the five-year biochemical disease-free survival increased, without significantly increasing toxicity. The aim of the present study was to investigate the association between radiation dose to the bladder and urethra and genitourinary (GU) toxicity grade >= 2 in the entire cohort.Material and methods: The dose-effect relations of the urethra and bladder dose, separately, and GU toxicity grade >= 2 (CTCAE 3.0) up to five years after treatment were assessed. A mixed model analysis for repeated measurements was used, adjusting for age, diabetes mellitus, T-stage, baseline GU toxicity grade >= 1 and institute. Additionally, the association between the dose and separate GU toxicity subdomains were investigated.Results: Dose-effect relations were observed for the dose (Gy) to the bladder D2 cm(3) and urethra D0.1 cm(3), with adjusted odds ratios of 1.14 (95% CI 1.12-1.16, p < 0.0001) and 1.12 (95% CI 1.11-1.14, p < 0.0001), respectively. Additionally, associations between the dose to the urethra and bladder and the subdomains urinary frequency, urinary retention and urinary incontinence were observed.Conclusion: Further increasing the dose to the bladder and urethra will result in a significant increase in GU toxicity following EBRT. Focal boost treatment plans should incorporate a urethral dose-constraint. Further treatment optimization to increase the focal boost dose without increasing the dose to the urethra and other organs at risk should be a focus for future research, as we have shown that a focal boost is beneficial in the treatment of prostate cancer. (C) 2021 The Author(s). Published by Elsevier B.V. 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
Walterbos, N.R.; Fiocco, M.; Neelis, K.J.; Linden, Y.M. van der; Langers, A.M.J.; Slingerland, M.; ... ; Lips, I.M. 2019
Background and purpose: High-risk prostate cancer patients are frequently treated with external-beam radiotherapy (EBRT). Of all patients receiving EBRT, 15–35% will experience biochemical... Show moreBackground and purpose: High-risk prostate cancer patients are frequently treated with external-beam radiotherapy (EBRT). Of all patients receiving EBRT, 15–35% will experience biochemical recurrence (BCR) within five years. Magnetic resonance imaging (MRI) is commonly acquired as part of the diagnostic procedure and imaging-derived features have shown promise in tumour characterisation and biochemical recurrence prediction. We investigated the value of imaging features extracted from pre-treatment T2w anatomical MRI to predict five year biochemical recurrence in high-risk patients treated with EBRT. Materials and methods: In a cohort of 120 high-risk patients, imaging features were extracted from the wholeprostate and a margin surrounding it. Intensity, shape and textural features were extracted from the original and filtered T2w-MRI scans. The minimum-redundancy maximum-relevance algorithm was used for feature selection. Random forest and logistic regression classifiers were used in our experiments. The performance of a logistic regression model using the patient’s clinical features was also investigated. To assess the prediction accuracy we used stratified 10-fold cross validation and receiver operating characteristic analysis, quantified by the area under the curve (AUC). Results: A logistic regression model built using whole-prostate imaging features obtained an AUC of 0.63 in the prediction of BCR, outperforming a model solely based on clinical variables (AUC = 0.51). Combining imaging and clinical features did not outperform the accuracy of imaging alone. Conclusions: These results illustrate the potential of imaging features alone to distinguish patients with an increased risk of recurrence, even in a clinically homogeneous cohort. Show less
Fernandes, C.D.; Dinh, C.V.; Steggerda, M.J.; Beek, L.C. ter; Smolic, M.; Buuren, L.D. van; ... ; Heide, U.A. van der 2017
This thesis describes the results of the first en second Post Operative Radiation Therapy in Endometrial Cancer (PORTEC) trials. The 15-year results of PORTEC-1 confirm the importance of the... Show moreThis thesis describes the results of the first en second Post Operative Radiation Therapy in Endometrial Cancer (PORTEC) trials. The 15-year results of PORTEC-1 confirm the importance of the prognostic factors age, grade and depth of myometrial invasion for selection of patients with high-intermediate risk (HIR) features. Postoperative pelvic external beam radiotherapy (EBRT) reduces the risk of locoregional recurrence (mainly due to a decrease in vaginal recurrences), without a survival benefit compared to no additional therapy. The PORTEC-2 trial has shown that EBRT and vaginal brachytherapy (VBT) offer excellent rates of vaginal control and similar overall survival for HIR patients, while VBT has a clearly more favourable health related quality of life profile, with results similar to an age-matched norm population. EBRT is associated with a higher risk of long-lasting bowel symptoms that impact on patients__ daily lives and physical functioning. Therefore, VBT is the treatment of choice for HIR patients. Finally, a pilot study in PORTEC-2 patients showed that the presence of multiple activated oncogenic pathways was the most powerful independent prognostic factor for decreased disease free survival, indicating that molecular prognostic factors refine the currently used system for risk classification. Show less
