Publications (8)37.98 Total impact
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Article: Residual setup errors caused by rotation and non-rigid motion in prone-treated cervical cancer patients after online CBCT image-guidance.
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ABSTRACT: To quantify the impact of uncorrected or partially corrected pelvis rotation and spine bending on region-specific residual setup errors in prone-treated cervical cancer patients. Fifteen patients received an in-room CBCT scan twice a week. CBCT scans were registered to the planning CT-scan using a pelvic clip box and considering both translations and rotations. For daily correction of the detected translational pelvis setup errors by couch shifts, residual setup errors were determined for L5, L4 and seven other points of interest (POIs). The same was done for a procedure with translational corrections and limited rotational correction (±3°) by a 6D positioning device. With translational correction only, residual setup errors were large especially for L5/L4 in AP direction (Σ=5.1/5.5mm). For the 7 POIs the residual setup errors ranged from 1.8 to 5.6mm (AP). Using the 6D positioning device, the errors were substantially smaller (for L5/L4 in AP direction Σ=2.7/2.2mm). Using this device, the percentage of fractions with a residual AP displacement for L4>5mm reduced from 47% to 9%. Setup variations caused by pelvis rotations are large and cannot be ignored in prone treatment of cervical cancer patients. Corrections with a 6D positioning device may considerably reduce resulting setup errors, but the residual setup errors should still be accounted for by appropriate CTV-to-PTV margins.Radiotherapy and Oncology 05/2012; 103(3):322-6. · 5.58 Impact Factor -
Article: Toward an individualized target motion management for IMRT of cervical cancer based on model-predicted cervix-uterus shape and position.
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ABSTRACT: To design and evaluate a 3D patient-specific model to predict the cervix-uterus shape and position. For 13 patients lying in prone position, 10 variable bladder filling CT-scans were acquired, 5 at planning and 5 after 40Gy. The delineated cervix-uterus volumes in 2-5 pre-treatment CT-scans were used to generate patient-specific models that predict the cervix-uterus geometry by bladder volume. Model predictions were compared to delineations, excluding those used for model construction. The prediction error was quantified by the margin required around the predicted volumes to accommodate 95% of the delineated volume and by the predicted-to-delineated surface distance. The prediction margin was significantly smaller (average 50%) than the margin encompassing the cervix-uterus motion. The prediction margin could be decreased (from 7 to 5mm at planning and from 10 to 8mm after 40Gy) by increasing (from 2 to 5) the number of CT-scans used for the model construction. For most patients, even with a model based on only two CT-scans, the prediction error was well below the margin encompassing the cervix-uterus motion. The described approach could be used to create prior to treatment, an individualized treatment strategy.Radiotherapy and Oncology 05/2011; 99(2):240-5. · 5.58 Impact Factor -
Article: Increasing treatment accuracy for cervical cancer patients using correlations between bladder-filling change and cervix-uterus displacements: proof of principle.
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ABSTRACT: To investigate application of pre-treatment established correlations between bladder-filling changes and cervix-uterus displacements in adaptive therapy. Thirteen cervical cancer patients participated in this prospective study. Pre-treatment, and after delivery of 40 Gy, a full bladder CT-scan was acquired, followed by voiding the bladder and acquisition of 4 other 3D scans in a 1h period with a naturally filling bladder (variable bladder filling CT-scans, VBF-scans). For the pre-treatment VBF-scans, linear correlations between bladder volume change and displacements of the tip of the uterus (ToU) and the center of mass (CoM) of markers implanted in the fornices of the vagina relative to the full bladder planning scan were established. Prediction accuracy of these correlation models was assessed by comparison with actual displacements in CT-scans, both pre-treatment and after 40 Gy. Inter-fraction ToU and marker-CoM displacements were derived from the established correlations and twice-weekly performed in-room bladder volume measurements, using a 3D ultrasound scanner. Target displacement in VBF-scans ranged from up to 65 mm in a single direction to almost 0mm, depending on the patient. For pre-treatment VBF-scans, the linear correlation models predicted the mean 3D position change for the ToU of 26.1 mm±10.8 with a residual of only 2.2 mm±1.7. For the marker-CoM, the 8.4 mm±5.3 mean positioning error was predicted with a residual of 0.9 mm±0.7. After 40Gy, the mean ToU displacement was 26.8 mm±15.8, while prediction based on the pre-treatment correlation models yielded a mean residual error of 9.0 mm±3.7. Target positioning errors in the fractioned treatments were very large, especially for the ToU (-18.5mm±11.2 for systematic errors in SI-direction). Pre-treatment acquired VBF-scans may be used to substantially enhance treatment precision of cervical cancer patients. Application in adaptive therapy is promising and warrants further investigation. For highly conformal (IMRT) treatments, the use of a full bladder drinking protocol results in unacceptably large systematic set-up errors.Radiotherapy and Oncology 02/2011; 98(3):340-6. · 5.58 Impact Factor -
Article: Hyperthermia dose-effect relationship in 420 patients with cervical cancer treated with combined radiotherapy and hyperthermia.
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ABSTRACT: Adding hyperthermia to standard radiotherapy (RT+HT) improves treatment outcome for patients with locally advanced cervical cancer (LACC). We investigated the effect of hyperthermia dose on treatment outcome for patients with LACC treated with RT+HT. We collected treatment and outcome data of 420 patients with LACC treated with hyperthermia at our institute from 1990 to 2005. Univariate and multivariate analyses were performed on response rate, local control, disease-specific survival and toxicity for these patients to search for a thermal dose response relationship. Besides commonly identified prognostic factors in LACC like tumour stage, performance status, radiotherapy dose and tumour size, thermal parameters involving both temperature and duration of heating emerged as significant predictors of the various end-points. The more commonly used CEM43T90 (cumulative equivalent minutes of T90 above 43 degrees C) was less influential than TRISE (based on the average T50 increase and the duration of heating, normalised to the scheduled duration of treatment). CEM43T90 and TRISE measured intraluminally correlate significantly and independently with tumour control and survival. These findings stimulate further technological development and improvement of deep hyperthermia, as they strongly suggest that it might be worthwhile to increase the thermal dose for LACC, either by treatment optimisation or by prolonging the treatment time. These results also confirm the beneficial effects from hyperthermia as demonstrated in our earlier randomised trial, and justify applying radiotherapy and hyperthermia as treatment of choice for patients with advanced cervical cancer.European journal of cancer (Oxford, England: 1990) 05/2009; 45(11):1969-78. · 4.12 Impact Factor -
Article: Surgical clips for position verification and correction of non-rigid breast tissue in simultaneously integrated boost (SIB) treatments.
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ABSTRACT: The aim of this study is to investigate whether surgical clips in the lumpectomy cavity are representative for position verification of both the tumour bed and the whole breast in simultaneously integrated boost (SIB) treatments. For a group of 30 patients treated with a SIB technique, kV and MV planar images were acquired throughout the course of the fractionated treatment. The 3D set-up error for the tumour bed was derived by matching the surgical clips (3-8 per patient) in two almost orthogonal planar kV images. By projecting the 3D set-up error derived from the planar kV images to the (u, v)-plane of the tangential beams, the correlation with the 2D set-up error for the whole breast, derived from the MV EPID images, was determined. The stability of relative clip positions during the fractionated treatment was investigated. In addition, for a subgroup of 15 patients, the impact of breathing was determined from fluoroscopic movies acquired at the linac. The clip configurations were stable over the course of radiotherapy, showing an inter-fraction variation (1 SD) of 0.5mm on average. Between the start and the end of the treatment, the mean distance between the clips and their center of mass was reduced by 0.9 mm. A decrease larger than 2mm was observed in eight patients (17 clips). The top-top excursion of the clips due to breathing was generally less than 2.5mm in all directions. The population averages of the difference (+/-1 SD) between kV and MV matches in the (u, v)-plane were 0.2+/-1.8mm and 0.9+/-1.5mm, respectively. In 30% of the patients, time trends larger than 3mm were present over the course of the treatment in either or in both kV and MV match results. Application of the NAL protocol based on the clips reduced the population mean systematic error to less than 2mm in all directions, both for the tumour bed and the whole breast. Due to the observed time trends, these systematic errors can be further reduced to about 1mm by using an eNAL protocol instead. The relative positions of implanted surgical clips in the lumpectomy cavity after breast-conserving surgery remain stable during the course of radiotherapy treatment. Application of a NAL or eNAL set-up correction protocol based on surgical clips allows for adequate treatment of both the tumour bed and the whole breast with tight CTV-PTV margins.Radiotherapy and Oncology 12/2008; 90(1):110-5. · 5.58 Impact Factor -
Article: Inter-fraction bladder filling variations and time trends for cervical cancer patients assessed with a portable 3-dimensional ultrasound bladder scanner.
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ABSTRACT: For cervical cancer patients, bladder filling variations may result in inadequate EBRT target coverage, unless large safety margins are used. For a group of patients who received full bladder instructions, inter-fraction variations and time trends in bladder volume were quantified, and a 3D ultrasound (US) scanner was tested for on-line bladder volume measurements. For 24 patients, the bladder volume was measured with US at the time of the planning CT scan, and twice weekly during the course of RT. Comparisons of US with planning CT were used to assess the bladder scanner accuracy. Patients were treated in prone on a belly board, EPID images were acquired to correlate set-up errors with bladder filling variations. Measured US and CT bladder volumes were strongly correlated (R = 0.97, slope 1.1 +/- 0.1). The population mean bladder volume at planning of 378 +/- 209 ml (1 SD) reduced to 109 +/- 88 ml (1 SD) in week 6, a reduction by 71% (average reduction 46 ml/week), revealing a large inter-fraction time trend. Intra-patient variation in bladder volume during RT was 168 ml (1 SD) (range 70-266 ml). Rotation around the LR axis was significantly correlated with bladder volume changes. Despite a full bladder instruction, bladder volumes reduced dramatically during treatment, implying large time trends in target position of these patients. The portable US scanner provides a quick and reliable measurement of the bladder volume, which might assist future online treatment adaptation.Radiotherapy and Oncology 09/2008; 89(2):172-9. · 5.58 Impact Factor -
Article: Acute and late complications after radiotherapy for prostate cancer: results of a multicenter randomized trial comparing 68 Gy to 78 Gy.
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ABSTRACT: To compare acute and late gastrointestinal (GI) and genitourinary (GU) side effects in prostate cancer patients randomized to receive 68 Gy or 78 Gy. Between June 1997 and February 2003, 669 prostate cancer patients were randomized between radiotherapy with a dose of 68 Gy and 78 Gy, in 2 Gy per fraction and using three-dimensional conformal radiotherapy. All T stages with prostate-specific antigen (PSA) <60 ng/mL were included, except any T1a and well-differentiated T1b-c tumors with PSA < or =4 ng/mL. Stratification was done for four dose-volume groups (according to the risk of seminal vesicles [SV] involvement), age, hormonal treatment (HT), and hospital. The clinical target volume (CTV) consisted of the prostate with or without the SV, depending on the estimated risk of SV invasion. The CTV-planning target volume (PTV) margin was 1 cm for the first 68 Gy and was reduced to 0.5 cm (0 cm toward the rectum) for the last 10 Gy in the 78 Gy arm. Four Dutch hospitals participated in this Phase III trial. Evaluation of acute and late toxicity was based on 658 and 643 patients, respectively. For acute toxicity (<120 days), the Radiation Therapy Oncology Group (RTOG) scoring system was used and the maximum score was reported. Late toxicity (>120 days) was scored according to the slightly adapted RTOG/European Organization for Research and Treatment of Cancer (EORTC) criteria. The median follow-up time was 31 months. For acute toxicity no significant differences were seen between the two randomization arms. GI toxicity Grade 2 and 3 was reported as the maximum acute toxicity in 44% and 5% of the patients, respectively. For acute GU toxicity, these figures were 41% and 13%. No significant differences between both randomization arms were seen for late GI and GU toxicity, except for rectal bleeding requiring laser treatment or transfusion (p = 0.007) and nocturia (p = 0.05). The 3-year cumulative risk of late RTOG/EORTC GI toxicity grade > or =2 was 23.2% for 68 Gy, and 26.5% for 78 Gy (p = 0.3). The 3-year risks of late RTOG/EORTC GU toxicity grade > or =2 were 28.5% and 30.2% for 68 Gy and 78 Gy, respectively (p = 0.3). Factors related to acute GI toxicity were HT (p < 0.001), a higher dose-volume group (p = 0.01), and pretreatment GI symptoms (p = 0.04). For acute GU toxicity, prognostic factors were: pretreatment GU symptoms (p < 0.001), HT (p = 0.003), and prior transurethral resection of the prostate (TURP) (p = 0.02). A history of abdominal surgery (p < 0.001) and pretreatment GI symptoms (p = 0.001) were associated with a higher incidence of late GI grade > or =2 toxicity, whereas HT (p < 0.001), pretreatment GU symptoms (p < 0.001), and prior TURP (p = 0.006) were prognostic factors for late GU grade > or =2. Raising the dose to the prostate from 68 Gy to 78 Gy resulted in higher incidences of acute and late GI and GU toxicity, but these differences were not significant, except for late rectal bleeding requiring treatment and late nocturia. Other factors than the studied dose levels appeared to be important in predicting toxicity after radiotherapy, especially previous surgical interventions (abdominal surgery or TURP), hormonal therapy, and the presence of pretreatment symptoms.International Journal of Radiation OncologyBiologyPhysics 04/2005; 61(4):1019-34. · 4.11 Impact Factor -
Article: Radiation therapy in early stage Hodgkin's disease: long-term results and adverse effects.
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ABSTRACT: Radiation therapy (RT) was the first treatment modality demonstrating cure of Hodgkin's disease. Long-term side-effects of this treatment, however, have become evident in the past few years. By reviewing the results of megavoltage radiotherapy as initial treatment in a consecutive series of 106 patients with early-stage Hodgkin's disease (HD), survival, relapse-free interval, salvage rate of relapsing cases, and incidence of second tumours were evaluated. Subtotal node irradiation was given to all patients with supradiaphragmatic disease, except for 15 patients with limited stage IA-IIA, who received mantle field treatment only. Inverted Y field irradiation was given to all seven patients with subdiaphragmatic disease. The median age was 32 years (range 14-77). The median follow-up was 140 months. The relapse-free interval of the patient population was 78% at 5 years and 72% at 10 years. The overall survival (OS) was 90% and 79%, respectively. Salvage therapy was successful in 26 of 30 relapsing patients. Twelve recurrences were located inside the treatment field. Sixteen patients (15%) developed second malignancies: cancer of the lung (two), ovary (two), cervix (one), colon (two), breast (three), stomach (one), skin (two), hypopharynx (one), and non-Hodgkin lymphoma (two). Eleven of these were located within the radiation field. Although RT is intended to be a curative treatment, up to 30% recurrences occur. Mortality was not determined by primary HD, but by second malignancies, which are likely related to treatment. New treatment strategies, aiming at long-term freedom from relapse without carcinogenic side-effects, are urgently needed.The Hematology Journal 02/2002; 3(4):179-84. · 1.86 Impact Factor
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2008–2012
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Erasmus MC
Rotterdam, South Holland, Netherlands
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