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Maastricht, Netherlands

Nout R.A.,Leiden University | Smit V.T.H.B.M.,Leiden University | Putter H.,Leiden University | Jurgenliemk-Schulz I.M.,University Utrecht | And 10 more authors.
The Lancet | Year: 2010

Background: After surgery for intermediate-risk endometrial carcinoma, the vagina is the most frequent site of recurrence. This study established whether vaginal brachytherapy (VBT) is as effective as pelvic external beam radiotherapy (EBRT) in prevention of vaginal recurrence, with fewer adverse effects and improved quality of life. Methods: In this open-label, non-inferiority, randomised trial undertaken in 19 Dutch radiation oncology centres, 427 patients with stage I or IIA endometrial carcinoma with features of high-intermediate risk were randomly assigned by a computer-generated, biased coin minimisation procedure to pelvic EBRT (46 Gy in 23 fractions; n=214) or VBT (21 Gy high-dose rate in three fractions, or 30 Gy low-dose rate; n=213). All investigators were masked to the assignment of treatment group. The primary endpoint was vaginal recurrence. The predefined non-inferiority margin was an absolute difference of 6% in vaginal recurrence. Analysis was by intention to treat, with competing risk methods. The study is registered, number ISRCTN16228756. Findings: At median follow-up of 45 months (range 18-78), three vaginal recurrences had been diagnosed after VBT and four after EBRT. Estimated 5-year rates of vaginal recurrence were 1·8% (95% CI 0·6-5·9) for VBT and 1·6% (0·5-4·9) for EBRT (hazard ratio [HR] 0·78, 95% CI 0·17-3·49; p=0·74). 5-year rates of locoregional relapse (vaginal or pelvic recurrence, or both) were 5·1% (2·8-9·6) for VBT and 2·1% (0·8-5·8) for EBRT (HR 2·08, 0·71-6·09; p=0·17). 1·5% (0·5-4·5) versus 0·5% (0·1-3·4) of patients presented with isolated pelvic recurrence (HR 3·10, 0·32-29·9; p=0·30), and rates of distant metastases were similar (8·3% [5·1-13·4] vs 5·7% [3·3-9·9]; HR 1·32, 0·63-2·74; p=0·46). We recorded no differences in overall (84·8% [95% CI 79·3-90·3] vs 79·6% [71·2-88·0]; HR 1·17, 0·69-1·98; p=0·57) or disease-free survival (82·7% [76·9-88·6] vs 78·1% [69·7-86·5]; HR 1·09, 0·66-1·78; p=0·74). Rates of acute grade 1-2 gastrointestinal toxicity were significantly lower in the VBT group than in the EBRT group at completion of radiotherapy (12·6% [27/215] vs 53·8% [112/208]). Interpretation: VBT is effective in ensuring vaginal control, with fewer gastrointestinal toxic effects than with EBRT. VBT should be the adjuvant treatment of choice for patients with endometrial carcinoma of high-intermediate risk. Funding: Dutch Cancer Society. © 2010 Elsevier Ltd. All rights reserved. Source


Hatt M.,French Institute of Health and Medical Research | Cheze-Le Rest C.,French Institute of Health and Medical Research | Van Baardwijk A.,MAASTricht Radiation Oncology Clinic | Lambin P.,MAASTricht Radiation Oncology Clinic | And 2 more authors.
Journal of Nuclear Medicine | Year: 2011

The objectives of this study were to investigate the relationship between CT- and 18F-FDG PET-based tumor volumes in non-small cell lung cancer (NSCLC) and the impact of tumor size and uptake heterogeneity on various approaches to delineating uptake on PET images. Methods: Twenty-five NSCLC cancer patients with 18F-FDG PET/CT were considered. Seventeen underwent surgical resection of their tumor, and the maximum diameter was measured. Two observers manually delineated the tumors on the CT images and the tumor uptake on the corresponding PET images, using a fixed threshold at 50% of the maximum (T 50), an adaptive threshold methodology, and the fuzzy locally adaptive Bayesian (FLAB) algorithm. Maximum diameters of the delineated volumes were compared with the histopathology reference when available. The volumes of the tumors were compared, and correlations between the anatomic volume and PET uptake heterogeneity and the differences between delineations were investigated. Results: All maximum diameters measured on PET and CT images significantly correlated with the histopathology reference (r > 0.89, P < 0.0001). Significant differences were observed among the approaches: CT delineation resulted in large overestimation (+32% ± 37%), whereas all delineations on PET images resulted in underestimation (from -15% ± 17% for T 50 to -4% ± 8% for FLAB) except manual delineation (+8% ± 17%). Overall, CT volumes were significantly larger than PET volumes (55 ± 74 cm 3 for CT vs. from 18 ± 25 to 47 ± 76 cm 3 for PET). A significant correlation was found between anatomic tumor size and heterogeneity (larger lesions were more heterogeneous). Finally, the more heterogeneous the tumor uptake, the larger was the underestimation of PET volumes by threshold-based techniques. Conclusion: Volumes based on CT images were larger than those based on PET images. Tumor size and tracer uptake heterogeneity have an impact on threshold-based methods, which should not be used for the delineation of cases of large heterogeneous NSCLC, as these methods tend to largely underestimate the spatial extent of the functional tumor in such cases. For an accurate delineation of PET volumes in NSCLC, advanced image segmentation algorithms able to deal with tracer uptake heterogeneity should be preferred. Copyright © 2011 by the Society of Nuclear Medicine, Inc. Source


Kunneman M.,Leiden University | Pieterse A.H.,Leiden University | Stiggelbout A.M.,Leiden University | Nout R.A.,Leiden University | And 7 more authors.
British Journal of Cancer | Year: 2014

Background:Vaginal brachytherapy (VBT) in high-intermediate-risk endometrial cancer (EC) provides a significant reduction in the risk of local cancer recurrence, but without survival benefit and with increased mucosal atrophy. Five-year local control is estimated to be similar for VBT and a watchful waiting policy (WWP), in which patients receive VBT combined with external radiation in case of a recurrence. Our aim was to assess treatment preferences of EC patients and clinicians regarding VBT and WWP, and to evaluate their preferred and perceived involvement in treatment decision making.Methods:Interviews were held with 95 treated EC patients. The treatment trade-off method was used to assess the minimally desired benefit from VBT in local control. Patients' preferred and perceived involvement in decision making were assessed using a questionnaire. Seventy-seven clinicians completed a questionnaire assessing their minimally desired benefit and preferred involvement in decision making.Results:Minimally desired benefit of VBT was significantly lower for patients than for clinicians (median=0 vs 8%, P<0.001), for irradiated than for non-irradiated patients (median=0 vs 6.5%, P<0.001), and for radiation oncologists than for gynaecologists (median=4 vs 13%, P<0.001). Substantial variation existed within the groups of patients and clinicians. Participants preferred the patient and clinician to share in the decision about VBT. However, irradiated patients indicated low perceived involvement in actual treatment decision making.Conclusions:We found variations between and within patients and clinicians in minimally desired benefit from VBT. However, the recurrence risk at which patients preferred VBT was low. Our results showed that patients consider active participation in decision making essential. © 2014 Cancer Research UK. All rights reserved. Source


Hatt M.,Institute National Of La Sante Et Of La Recherche Medicale U650 Brest | Cheze le Rest C.,Institute National Of La Sante Et Of La Recherche Medicale U650 Brest | Cheze le Rest C.,Center Hospitalier University | Descourt P.,Institute National Of La Sante Et Of La Recherche Medicale U650 Brest | And 7 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: Accurate contouring of positron emission tomography (PET) functional volumes is now considered crucial in image-guided radiotherapy and other oncology applications because the use of functional imaging allows for biological target definition. In addition, the definition of variable uptake regions within the tumor itself may facilitate dose painting for dosimetry optimization. Methods and Materials: Current state-of-the-art algorithms for functional volume segmentation use adaptive thresholding. We developed an approach called fuzzy locally adaptive Bayesian (FLAB), validated on homogeneous objects, and then improved it by allowing the use of up to three tumor classes for the delineation of inhomogeneous tumors (3-FLAB). Simulated and real tumors with histology data containing homogeneous and heterogeneous activity distributions were used to assess the algorithm's accuracy. Results: The new 3-FLAB algorithm is able to extract the overall tumor from the background tissues and delineate variable uptake regions within the tumors, with higher accuracy and robustness compared with adaptive threshold (Tbckg) and fuzzy C-means (FCM). 3-FLAB performed with a mean classification error of less than 9% ± 8% on the simulated tumors, whereas binary-only implementation led to errors of 15% ± 11%. Tbckg and FCM led to mean errors of 20% ± 12% and 17% ± 14%, respectively. 3-FLAB also led to more robust estimation of the maximum diameters of tumors with histology measurements, with <6% standard deviation, whereas binary FLAB, Tbckg and FCM lead to 10%, 12%, and 13%, respectively. Conclusion: These encouraging results warrant further investigation in future studies that will investigate the impact of 3-FLAB in radiotherapy treatment planning, diagnosis, and therapy response evaluation. © 2010 Elsevier Inc. All rights reserved. Source

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