Post operative radiation therapy in endometrial carcinoma : reducing overtreatment and improving quality of life

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 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.KWF Kankerbestrijding Bontius StichtingUBL - phd migration 201

Plan-library supported automated replanning for online-adaptive intensity-modulated proton therapy of cervical cancer

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 dayto-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 (V95% 95% and V107% 2%) for 37/46 plans using the 1-planlibrary 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 V107% > 2% for 3/46 plans. Similar OAR results were obtained. Conclusion: The automated prior-plan adaptation method can successfully adapt for the large day-today variations observed in cervical cancer patients

Practical guidance for mismatch repair-deficiency testing in endometrial cancer

MTG8 - Moleculaire pathologie van gynecologische tumore

Predictive factors for response and toxicity after brachytherapy for rectal cancer; results from the HERBERT study

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Image-guided adaptive brachytherapy (IGABT) for primary vaginal cancer: results of the international multicenter RetroEMBRAVE cohort study.

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Impact of (chemo)radiotherapy on immune cell composition and function in cervical cancer patients

Experimental cancer immunology and therap

PROTECT: prospective phase-II-trial evaluating adaptive proton therapy for cervical cancer to reduce the impact on morbidity and the immune system

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Prognostic refinement of NSMP high-risk endometrial cancers using oestrogen receptor immunohistochemistry

Background: Risk-assessment of endometrial cancer (EC) is based on clinicopathological factors and molecular subgroup. It is unclear whether adding hormone receptor expression, L1CAM expression or CTNNB1 status yields prognostic refinement. Methods: Paraffin-embedded tumour samples of women with high-risk EC (HR-EC) from the PORTEC-3 trial (n = 424), and a Dutch prospective clinical cohort called MST (n = 256), were used. All cases were molecularly classified. Expression of L1CAM, ER and PR were analysed by whole-slide immunohistochemistry and CTNNB1 mutations were assessed with a next-generation sequencing. Kaplan-Meier method, log-rank tests and Cox's proportional hazard models were used for survival analysis. Results: In total, 648 HR-EC were included. No independent prognostic value of ER, PR, L1CAM, and CTNNB1 was found, while age, stage, and adjuvant chemotherapy had an independent impact on risk of recurrence. Subgroup-analysis showed that only in NSMP HR-EC, ER-positivity was independently associated with a reduced risk of recurrence (HR 0.33, 95%CI 0.15-0.75). Conclusions: We confirmed the prognostic impact of the molecular classification, age, stage, and adjuvant CTRT in a large cohort of high-risk EC. ER-positivity is a strong favourable prognostic factor in NSMP HR-EC and identifies a homogeneous subgroup of NSMP tumours. Assessment of ER status in high-risk NSMP EC is feasible in clinical practice and could improve risk stratification and treatment.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer

Development and application of statistical models for medical scientific researc