Background: Intensity-modulated proton therapy is sensitive to inter-fraction variations, including density changes along the pencil-beam paths and variations in organ-shape and location. Large day... Show moreBackground: Intensity-modulated proton therapy is sensitive to inter-fraction variations, including density changes along the pencil-beam paths and variations in organ-shape and location. Large day-to-day variations are seen for cervical cancer patients. The purpose of this study was to develop and evaluate a novel method for online selection of a plan from a patient-specific library of prior plans for different anatomies, and adapt it for the daily anatomy. Material and methods: The patient-specific library of prior plans accounting for altered target geometries was generated using a pretreatment established target motion model. Each fraction, the best fitting prior plan was selected. This prior plan was adapted using (1) a restoration of spot-positions (Bragg peaks) by adapting the energies to the new water equivalent path lengths; and (2) a spot addition to fully cover the target of the day, followed by a fast optimization of the spot-weights with the reference point method (RPM) to obtain a Pareto-optimal plan for the daily anatomy. Spot addition and spot-weight optimization could be repeated iteratively. The patient cohort consisted of six patients with in total 23 repeat-CT scans, with a prescribed dose of 45 Gy(RBE) to the primary tumor and the nodal CTV. Using a 1-plan-library (one prior plan based on all motion in the motion model) was compared to choosing from a 2-plan-library (two prior plans based on part of the motion). Results: Applying the prior-plan adaptation method with one iteration of adding spots resulted in clinically acceptable target coverage ( and ) for 37/46 plans using the 1-plan-library and 41/46 plans for the 2-plan-library. When adding spots twice, the 2-plan-library approach could obtain acceptable coverage for all scans, while the 1-plan-library approach showed for 3/46 plans. Similar OAR results were obtained. Conclusion: The automated prior-plan adaptation method can successfully adapt for the large day-to-day variations observed in cervical cancer patients. Show less
Introduction: Although the majority of women with endometrial cancer have a favorable prognosis due to early symptoms, 15-20% have high-risk disease features and are at increased risk of recurrence... Show moreIntroduction: Although the majority of women with endometrial cancer have a favorable prognosis due to early symptoms, 15-20% have high-risk disease features and are at increased risk of recurrence. In order to improve prognosis for these patients, several trials have compared chemotherapy (CT), radiotherapy (RT) or the combination of CTRT. Areas covered: This review focuses on the current evidence on adjuvant treatment for women with high-risk endometrial cancer and future perspectives. Expert commentary: For stage I-II high-risk endometrial cancer, external beam radiotherapy ensured good local control and no significant benefit in progression-free or overall survival was found with the addition of chemotherapy in 2 recent randomized trials. For women with stage III disease, the combination of chemotherapy and radiotherapy improved progression-free survival with a non-significant improvement of overall survival. Adjuvant chemotherapy alone resulted in higher rates of pelvic and para-aortic recurrence. More toxicity and reduced quality of life were found during and after adjuvant CTRT. It is essential to discuss the benefits and disadvantages of chemotherapy and radiotherapy with individual patients for shared decision-making. Translational research is ongoing to further characterize individual tumors, identify sensitivity to (immuno)therapies and find new treatment targets to improve outcomes. Show less
AbstractBackground: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy ... Show moreAbstractBackground: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m2 in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.Patients and methods: A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (κ).Results: In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (κ = 0.72), lymph-vascular space invasion (κ = 0.72) and histological grade (κ = 0.70).Conclusion: Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over- or undertreatment, especially when treatment modalities with substantial toxicity are involved. This study is registered with ISRCTN (ISRCTN14387080, www.controlled-trials.com) and with ClinicalTrials.gov (NCT00411138). Show less
Although the majority of women with endometrial cancer have a favorable prognosis due to early symptoms, 15-20% have high-risk disease features and are at increased risk of recurrence. In order to... Show moreAlthough the majority of women with endometrial cancer have a favorable prognosis due to early symptoms, 15-20% have high-risk disease features and are at increased risk of recurrence. In order to improve prognosis for these patients, several trials have compared chemotherapy (CT), radiotherapy (RT) or the combination of CTRT. Areas covered: This review focuses on the current evidence on adjuvant treatment for women with high-risk endometrial cancer and future perspectives. Expert commentary: For stage I-II high-risk endometrial cancer, external beam radiotherapy ensured good local control and no significant benefit in progression-free or overall survival was found with the addition of chemotherapy in 2 recent randomized trials. For women with stage III disease, the combination of chemotherapy and radiotherapy improved progression-free survival with a non-significant improvement of overall survival. Adjuvant chemotherapy alone resulted in higher rates of pelvic and para-aortic recurrence. More toxicity and reduced quality of life were found during and after adjuvant CTRT. It is essential to discuss the benefits and disadvantages of chemotherapy and radiotherapy with individual patients for shared decision-making. Translational research is ongoing to further characterize individual tumors, identify sensitivity to (immuno)therapies and find new treatment targets to improve outcomes. Show less
Meir, H. van; Nout, R.A.; Welters, M.J.P.; Loof, N.M.; Kam, M.L. de; Ham, J.J. van; ... ; Burg, S.H. van der 2017
