Angela van Baardwijk

Maastro Clinic, Maestricht, Limburg, Netherlands

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Publications (68)231.34 Total impact

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    ABSTRACT: In this open-label phase I study, the maximum-tolerated dose of cetuximab with concurrent chemoradiotherapy (C-CRT) in stage III non-small-cell lung cancer together with individualized, isotoxic accelerated radiotherapy (RT) was investigated. Patients with stage III non-small-cell lung cancer, World Health Organization performance status 0-1, forced expiratory volume in 1 second more than 50%, carbon monoxide diffusing capacity more than 50%, weight loss less than 10%, and no severe comorbidity were enrolled. Patients without progression after one to two cycles of gemcitabine-carboplatin were included and treated with cetuximab 400 mg/kg d7 and 250 mg/kg weekly together with RT and cisplatin (50 mg/m d1, 8; 40 mg/m d22)-vinorelbine for 5 weeks. Vinorelbine was escalated in three steps; (1) 10 mg/m d1, 8 and 8 mg/m d22, 29; (2) 20 mg/m d1, 8 and 8 mg/m d22, 29; (3) 20 mg/m d1, 8; 15 mg/m d22, 29. An individualized prescribed RT dose based on normal tissue dose constraints was applied (e.g., mean lung dose 19 Gy). The primary endpoint was the maximum-tolerated dose 3 months after the end of C-CRT; secondary endpoints were toxicity and metabolic response as assessed by positron emission tomography. Between September 2007 and October 2010, 25 patients (12 men, 13 women, mean age 59 years) were included. The mean RT dose was 62 ± 6.6 Gy. The vinorelbine dose could be escalated to dose level 3. Twelve of 25 patients experienced greater than or equal to grade 3 toxicity (esophagitis 3, rash 1, diarrhea 1, cough 1, dyspnea 1, vomiting 1, and pulmonary embolism 1). No dose-limiting toxicities were observed. One patient with a complete pathological response in dose level 3 developed a fatal hemoptysis 4 months after RT. Metabolic remissions were observed in 19 of 22 patients. C-CRT with cetuximab and cisplatin-vinorelbine is safe to deliver at full dose. The recommended phase II dose is therefore cetuximab 400 mg/m d7 and 250 mg/m weekly, cisplatin 50 mg/m d1, 8; 40 mg/m d22 and vinorelbine 20 mg/m d1, 8; 15 mg/m d22, 29 for 5 weeks together with RT.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2014; 9(5):710-6. · 4.55 Impact Factor
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    ABSTRACT: Non-small cell lung cancer (NSCLC) stage T4N0-1 or single nodal station IIIA-N2 are two stage III sub-groups for which the outcome of non-surgical therapy is not well known. We investigated the results of individualised isotoxic accelerated radiotherapy (INDAR) and chemotherapy in this setting. Analysis of NSCLC patients included in 2 prospective trials (NCT00573040 and NCT00572325) stage T4N0-1 or IIIA-N2 with 1 pathologic nodal station, treated with chemo-radiotherapy (CRT) using INDAR with concurrent or sequential platinum-based chemotherapy. Overall survival (OS) was updated and calculated from date of diagnosis (Kaplan-Meier). Toxicity was scored following CTCAEv3.0. To allow comparison with other articles the subgroups were also analysed separately for toxicity, progression free and overall survival. 83 patients (42 T4N0-1 and 41 IIIA-N2) were identified: the median radiotherapy dose was 65Gy. Thirty-seven percent of patients received sequential CRT and 63% received concurrent CRT. At a median follow-up of 48months the median OS for T4N0-1 patients was 34months with 55% 2-year survival and 25% 5-year survival. For stage IIIA-N2 at a median follow-up of 50months the median OS was 26months with 2- and 5-year survival rates of 53% and 24%, respectively. Chemo-radiation using INDAR yields promising survival results in patients with single-station stage IIIA-N2 or T4N0-1 NSCLC.
    Radiotherapy and Oncology 01/2014; · 4.52 Impact Factor
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    ABSTRACT: [(18)F]HX4 is a promising hypoxia PET-tracer. Uptake, spatio-temporal stability and optimal acquisition parameters for [(18)F]HX4 PET imaging were evaluated in non-small cell lung cancer (NSCLC) patients. [(18)F]HX4 PET/CT images of 15 NSCLC patients were acquired 2h and 4h after injection (p.i.). Maximum standardized-uptake-value (SUVmax), tumor-to-blood-ratio (TBRmax), hypoxic fraction (HF) and contrast-to-noise-ratio (CNR) were determined for all lesions. To evaluate spatio-temporal stability, DICE-similarity and Pearson correlation coefficients were calculated. Optimal acquisition-duration was assessed by comparing 30, 20, 10 and 5min acquisitions. Considerable uptake (TBR >1.4) was observed in 18/25 target lesions. TBRmax increased significantly from 2h (1.6±0.3) to 4h p.i. (2.0±0.6). Uptake patterns at 2h and 4h p.i. showed a strong correlation (R=0.77±0.10) with a DICE similarity coefficient of 0.69±0.08 for the 30% highest uptake volume. Reducing acquisition-time resulted in significant changes in SUVmax and CNR. TBRmax and HF were only affected for scan-times of 5min. The majority of NSCLC lesions showed considerable [(18)F]HX4 uptake. The heterogeneous uptake pattern was stable between 2h and 4h p.i. [(18)F]HX4 PET imaging at 4h p.i. is superior to 2h p.i. to reach highest contrast. Acquisition time may be reduced to 10min without significant effects on TBRmax and HF.
    Radiotherapy and Oncology 09/2013; · 4.52 Impact Factor
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    ABSTRACT: To test the hypothesis that cardiac comorbidity before the start of radiotherapy (RT) is associated with an increased risk of radiation-induced lung toxicity (RILT) in lung cancer patients. A retrospective analysis was performed of a prospective cohort of 259 patients with locoregional lung cancer treated with definitive radio(chemo)therapy between 2007 and 2011 ( Identifiers: NCT00572325 and NCT00573040). We defined RILT as dyspnea CTCv.3.0 grade ⩾2 within 6months after RT, and cardiac comorbidity as a recorded treatment of a cardiac pathology at a cardiology department. Univariate and multivariate analyses, as well as external validation, were performed. The model-performance measure was the area under the receiver operating characteristic curve (AUC). Prior to RT, 75/259 (28.9%) patients had cardiac comorbidity, 44% of whom (33/75) developed RILT. The odds ratio of developing RILT for patients with cardiac comorbidity was 2.58 (p<0.01). The cross-validated AUC of a model with cardiac comorbidity, tumor location, forced expiratory volume in 1s, sequential chemotherapy and pretreatment dyspnea score was 0.72 (p<0.001) on the training set, and 0.67 (p<0.001) on the validation set. Cardiac comorbidity is an important risk factor for developing RILT after definite radio(chemo)therapy of lung cancer patients.
    Radiotherapy and Oncology 09/2013; · 4.52 Impact Factor
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    ABSTRACT: PURPOSE: This study explored international radiation oncology trainee decision making in the management of radiotherapy-induced nausea and vomiting (RINV). METHODS: Radiation oncology trainees who were members of the national radiation oncology associations of the USA, Canada, Netherlands, Australia, New Zealand, France, Spain and Singapore completed a Web-based survey. Respondents estimated the risks of nausea and vomiting associated with six standardised radiotherapy-only clinical case vignettes modelled after international anti-emetic guidelines and then committed to prophylactic, rescue or no therapy as an initial management approach for each case. RESULTS: One hundred and seventy-six trainees from 11 countries responded. Only 28 % were aware of any anti-emetic guideline. In general, risk estimates and management approaches for the high-risk and minimal risk cases varied less and were more in line with guideline standards than were estimates and approaches for the moderate- and low-risk cases. Prophylactic therapy was the most common approach for the high-risk and a moderate-risk case (83 and 71 % of respondents respectively), while rescue therapy was the most common approach for a second moderate-risk case (69 %), two low-risk cases (69 and 76 %) and a minimal risk case (68 %). A serotonin receptor antagonist was the most commonly recommended prophylactic agent. On multivariate analysis, a higher estimated risk of nausea predicted for recommending prophylactic therapy, and a lower estimated risk of nausea predicted for recommending rescue therapy. CONCLUSIONS: Radiation oncology trainee risk estimates and recommended management approaches for RINV clinical case vignettes varied and matched guideline standards more often for high-risk and minimal risk cases than for moderate- and low-risk cases. Risk estimates of nausea specifically were strong predictors of management decisions.
    Supportive Care in Cancer 02/2013; · 2.09 Impact Factor
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    ABSTRACT: Accurate volumetric assessment in non-small cell lung cancer (NSCLC) is critical for adequately informing treatments. In this study we assessed the clinical relevance of a semiautomatic computed tomography (CT)-based segmentation method using the competitive region-growing based algorithm, implemented in the free and public available 3D-Slicer software platform. We compared the 3D-Slicer segmented volumes by three independent observers, who segmented the primary tumour of 20 NSCLC patients twice, to manual slice-by-slice delineations of five physicians. Furthermore, we compared all tumour contours to the macroscopic diameter of the tumour in pathology, considered as the "gold standard". The 3D-Slicer segmented volumes demonstrated high agreement (overlap fractions > 0.90), lower volume variability (p = 0.0003) and smaller uncertainty areas (p = 0.0002), compared to manual slice-by-slice delineations. Furthermore, 3D-Slicer segmentations showed a strong correlation to pathology (r = 0.89, 95%CI, 0.81-0.94). Our results show that semiautomatic 3D-Slicer segmentations can be used for accurate contouring and are more stable than manual delineations. Therefore, 3D-Slicer can be employed as a starting point for treatment decisions or for high-throughput data mining research, such as Radiomics, where manual delineating often represent a time-consuming bottleneck.
    Scientific Reports 01/2013; 3:3529. · 2.93 Impact Factor
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    ABSTRACT: PURPOSE: In non-small cell lung cancer, gross tumor volume (GTV) influences survival more than other risk factors. This could also apply to small cell lung cancer. METHODS AND MATERIALS: Analysis of our prospective database with stage I to III SCLC patients referred for concurrent chemo radiation therapy. Standard treatment was 45 Gy in 1.5-Gy fractions twice daily concurrently with carboplatin-etoposide, followed by prophylactic cranial irradiation (PCI) in case of non-progression. Only fluorodeoxyglucose (FDG)-positron emission tomography (PET)-positive or pathologically proven nodal sites were included in the target volume. Total GTV consisted of post chemotherapy tumor volume and pre chemotherapy nodal volume. Survival was calculated from diagnosis (Kaplan-Meier ). RESULTS: A total of 119 patients were included between May 2004 and June 2009. Median total GTV was 93 ± 152 cc (7.5-895 cc). Isolated elective nodal failure occurred in 2 patients (1.7%). Median follow-up was 38 months, median overall survival 20 months (95% confidence interval = 17.8-22.1 months), and 2-year survival 38.4%. In multivariate analysis, only total GTV (P=.026) and performance status (P=.016) significantly influenced survival. CONCLUSIONS: In this series of stage I to III small cell lung cancer patients treated with FDG-PET-based selective nodal irradiation total GTV is an independent risk factor for survival.
    International journal of radiation oncology, biology, physics 11/2012; · 4.59 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: For stereotactic body radiotherapy (SBRT), typically a scheme of 60Gy in 3-8 fractions is applied, producing local tumour control rates around 90%. The dose specification is in one point only and ignores possible underdosages at the edge of the planning target volume (PTV). We investigated the doses at the edge of the PTV and correlated this with local tumour control with the aim to shed light on the radiation dose needed to eradicate stage I NSCLC. MATERIALS AND METHODS: Published data on the freedom from local progression (FFLP) data from SBRT and accelerated high-dose conventional radiotherapy series for stage I NSCLC with a follow up of at least 30months were included. The EQD(2,T) was calculated from the dose at the periphery of the PTV. RESULTS: Fifteen studies for SBRT (1076 patients) showed a median FFLP of 88.0±10.4% with a median EQD(2,T) of 76.9±17.4Gy. The median FFLP was 87.6±6.0% for the accelerated schedules with an EQD(2,T) of 86.9±39.1Gy, respectively. No significant relation was found between FFLP and the EQD(2,T) (p=0.23). CONCLUSIONS: Several fractionated and accelerated schedules with equal biological doses achieve the same tumour control rates as SBRT. Lower, but more uniform doses to the whole PTV may be sufficient to achieve similar control rates, with the possibility to deliver SBRT in adapted schedules, beneficial to centrally located tumours in the vicinity of critical structures like the oesophagus and great vessels.
    Radiotherapy and Oncology 10/2012; · 4.52 Impact Factor
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    ABSTRACT: BACKGROUND: Positron emission tomography (PET) may be useful for defining the gross tumour volume for radiation treatment planning and for response monitoring of non-small-cell lung cancer (NSCLC) patients. The purpose of this study was to compare tumour sizes obtained from CT- and various more commonly available PET-based tumour delineation methods to pathology findings. METHODS: Retrospective non-respiratory-gated whole body [18 F]-fluoro-2-deoxy-D-glucose PET/CT studies from 19 NSCLC patients were used. Several (semi-)automatic PET-based tumour delineation methods and manual CT-based delineation were used to assess the maximum tumour diameter. RESULTS: The PET-based 50 % and adaptive 41 % threshold-based delineation methods, and contrast-oriented delineation method showed good agreement with pathology after removing two outliers (R2 = 0.82). An absolute SUV threshold of 2.5 also showed a good agreement with pathology after the removal of five outliers (R2 = 0.79) but showed a significant overestimation in the maximum diameter (19.8 mm, p < 0.05). Adaptive 50 % threshold-based, relative threshold level and gradient-based methods did not show any outliers, provided only small, non-significant differences in maximum tumour diameter (<4.7 mm, p > 0.10) and showed fair correlation (R2 > 0.62) with pathology. Although the adaptive 70 % threshold-based method showed underestimation compared to pathology (36 %), it provided the best precision (SD = 14 %) together with good correlation (R2 = 0.81). Good correlation between CT delineation and pathology was observed (R2 = 0.77). However, CT delineation showed a significant overestimation compared with pathology (3.8 mm, p < 0.05). CONCLUSIONS: PET-based tumour delineation methods provided tumour sizes in agreement with pathology and may therefore be useful to define the (metabolically most) active part of the tumour for radiotherapy and monitoring purposes.
    EJNMMI research. 10/2012; 2(1):56.
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    ABSTRACT: BACKGROUND:: Stage IV non-small-cell lung cancer (NSCLC) patients with oligometastases (< 5 metastatic lesions) may experience long-term survival when all macroscopic tumor sites are treated radically, but no prospective data on NSCLCs with synchronous oligometastases are available. METHODS:: A prospective single-arm phase II trial was conducted. The main inclusion criteria were pathologically proven NSCLC stage IV with less than five metastases at primary diagnosis, amendable for radical local treatment (surgery or radiotherapy). The study is listed in, number NCT01282450. RESULTS:: Forty patients were enrolled, 39 of whom were evaluable (18 men, 21 women); mean age was 62.1 ± 9.2 years (range, 44-81). Twenty-nine (74%) had local stage III; 17 (44%) brain, seven (18%) bone, and four (10%) adrenal gland metastases. Thirty-five (87%) had a single metastatic lesion. Thirty-seven (95%) of the patients received chemotherapy as part of their primary treatment. Median overall survival (OS) was 13.5 months (95% confidence interval 7.6-19.4); 1-, 2-, and 3-year OS was 56.4%, 23.3%, and 17.5%, respectively. Median progression-free survival (PFS) was 12.1 months (95% confidence interval 9.6-14.3); 1-year PFS was 51.3%, and both 2- and 3-year PFS was 13.6%. Only two patients (5%) had a local recurrence. No patient or tumor parameter, including volume and F-deoxyglucose uptake was significantly correlated with OS or PFS. The treatment was well tolerated. CONCLUSION:: In this phase II study, long-term PFS was found in a subgroup of NSCLC patients with synchronous oligometastases when treated radically. Identification of this favorable subgroup before therapy is needed.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2012; 7(10):1547-1555. · 4.55 Impact Factor
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    ABSTRACT: The prognosis of patients with lung cancer has improved over the past years. Patient selection, optimal sequencing of systemic and local treatments, and better surgical techniques, together with unprecedented improvements in imaging and computer technology and technical advances in radiation therapy planning and delivery has revolutionized radiation therapy in a short period of time. Among the most significant evolutions that have direct implications for daily practice are the more widespread use of stereotactic body radiation for stage I non-small-cell lung cancer (NSCLC), concurrent chemoradiation for stage III NSCLC, the implementation of 4-dimensional computed tomography and positron emission tomography, adaptive radiation therapy strategies, optimizing the timing of chest radiation therapy for limited disease small-cell lung cancer (SCLC) and prophylactic cranial irradiation for extensive disease SCLC. Molecular-based individualized radiation therapy dose prescription, which goes hand in hand with the realization of decision-support systems and the introduction of proton therapy centers give only a glimpse of what the future will bring.
    Clinical Lung Cancer 07/2012; · 2.04 Impact Factor
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    ABSTRACT: To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately and committed to an initial management approach. In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT)₃ receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual patient risk assessment and to refine antiemetic guideline management recommendations.
    International journal of radiation oncology, biology, physics 06/2012; 84(1):e49-60. · 4.59 Impact Factor
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    ABSTRACT: Sequential chemotherapy and individualised accelerated radiotherapy (INDAR) has been shown to be effective in non-small cell lung cancer (NSCLC), allowing delivering of high biological doses. We therefore performed a phase II trial (; NCT00572325) investigating the same strategy in concurrent chemo-radiation in stage III NSCLC. 137 stage III patients fit for concurrent chemo-radiation (PS 0-2; FEV(1) and DLCO ⩾30%) were included from April 2006 till December 2009. An individualised prescribed dose based on normal tissue dose constraints was applied: mean lung dose (MLD) 19Gy, spinal cord 54Gy, brachial plexus 66Gy, central structures 74Gy. A total dose between 51 and 69Gy was delivered in 1.5Gy BID up to 45Gy, followed by 2Gy QD. Radiotherapy was started at the 2nd or 3rd course of chemotherapy. Primary end-point was overall survival (OS) and secondary end-point toxicity common terminology criteria for adverse events v3.0 (CTCAEv3.0). The median tumour volume was 76.4±94.1cc; 49.6% of patients had N2 and 32.1% N3 disease. The median dose was 65.0±6.0Gy delivered in 35±5.7days. Six patients (4.4%) did not complete radiotherapy. With a median follow-up of 30.9months, the median OS was 25.0months (2-year OS 52.4%). Severe acute toxicity (⩾G3, 35.8%) consisted mainly of G3 dysphagia during radiotherapy (25.5%). Severe late toxicity (⩾G3) was observed in 10 patients (7.3%). INDAR in concurrent chemo-radiation based on normal tissue constraints is feasible, even in patients with large tumour volumes and multi-level N2-3 disease, with acceptable severe late toxicity and promising 2-year survival.
    European journal of cancer (Oxford, England: 1990) 05/2012; 48(15):2339-46. · 4.12 Impact Factor
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    ABSTRACT: Radiation-induced oesophagitis is a major side effect of concurrent chemotherapy and radiotherapy. A strong association between neutropenia and oesophagitis was previously shown, but external validation and further elucidation of the possible mechanisms are lacking. A total of 119 patients were included at two institutions. The concurrent group comprised 34 SCLC patients treated with concurrent carboplatin and etoposide, and concurrent chest irradiation, and 36 NSCLC patients with concurrent cisplatin and etoposide, and concurrent radiotherapy, while the sequential group comprised 49 NSCLC patients received sequential cisplatin and gemcitabine, and radiotherapy. Severe neutropenia was very frequent during concurrent chemoradiation (grade: 4 41.4%) and during induction chemotherapy in sequentially treated patients (grade 4: 30.6%), but not during radiotherapy (only 4% grade 1). In the concurrent group, the odds ratios of grade 3 oesophagitis vs. neutropenia were the following: grade 2 vs. grade 0/1: 5.60 (95% CI 1.55-20.26), p = 0.009; grade 3 vs. grade 0/1: 10.40 (95% CI 3.19-33.95); p = 0.0001; grade 4 vs. grade 0/1: 12.60 (95% CI 4.36-36.43); p < 0.00001. There was no correlation between the occurrence of neutropenia during induction chemotherapy and acute oesophagitis during or after radiotherapy alone. In the univariate analysis, total radiation dose (p < 0.001), overall treatment time of radiotherapy (p < 0.001), mean oesophageal dose (p = 0.038) and neutropenia (p < 0.001) were significantly associated with the development of oesophagitis. In a multivariate analysis, only neutropenia remained significant (p = 0.023). We confirm that neutropenia is independently correlated with oesophagitis in concurrent chemoradiation, but that the susceptibility for chemotherapy-induced neutropenia is not associated with radiation-induced oesophagitis. Further studies focusing on the underlying mechanisms are thus warranted.
    Strahlentherapie und Onkologie 04/2012; 188(7):564-7. · 4.16 Impact Factor
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    ABSTRACT: Individualised, isotoxic, accelerated radiotherapy (INDAR) allows the delivery of high biological radiation doses, but the long-term survival associated with this approach is unknown. Patients with stage III NSCLC in the Netherlands Cancer Registry/Limburg from January 1, 2002 to December 31, 2008 were included. Patients (1002) with stage III NSCLC were diagnosed, of which 938 had T4 and/or N2-N3 disease. Patients treated with curative intent were staged with FDG-PET scans and a contrast-enhanced CT or an MRI of the brain. There were no shifts over time in the patient or tumour characteristics at diagnosis. The number of stage III NSCLC patients remained stable over time, but the proportion treated with palliative intent decreased from 47% in 2002 to 37% in 2008, and the percentage treated with chemo-radiation (RT) increased from 24.6% in 2002 to 47.8% in 2008 (p<0.001). The proportion of surgical patients remained below 5%. Sequential chemotherapy and conventional RT resulted in a median and a 5-year survival of 17.5 months and 8.4%, respectively, whereas with sequential chemotherapy and INDAR this was 23.6 months and 31%, respectively (p<0.001). Concurrent chemotherapy and INDAR was associated with a median and 2-year survival that was not reached and 66.7%, respectively (p=0.004). The proportion of patients treated with a curative intention with chemo-RT has increased markedly over time of observation. INDAR is associated with longer survival when compared to standard dose RT alone given with or without chemotherapy.
    Radiotherapy and Oncology 11/2011; 102(2):228-33. · 4.52 Impact Factor
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    ABSTRACT: The objectives of this study were to investigate the relationship between CT- and (18)F-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. Twenty-five NSCLC cancer patients with (18)F-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. 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. 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.
    Journal of Nuclear Medicine 11/2011; 52(11):1690-7. · 5.77 Impact Factor
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    ABSTRACT: To indicate which clinical target volume (CTV) margin (if any) is needed for an adequate treatment of non-small-cell lung cancer (NSCLC) using either 3D conformal or stereotactic radiotherapy, taking the distribution of the microscopic disease extension (MDE) into account. On the basis of the linear-quadratic biological model, a Monte-Carlo simulation was used to study the impact of MDE and setup deviations on the tumor control probability (TCP) after typical 3D conformal and stereotactic irradiation techniques. Setup deviations were properly accounted for in the planning target volume (PTV) margin. Previously measured distributions of MDE outside the macroscopic tumor in NSCLC patients were used. The dependence of the TCP on the CTV margins was quantified. The presence of MDE had a demonstratable influence on the TCP in both the 3D conformal and the stereotactic technique when no CTV margins were employed. The impact of MDE on the TCP values was greater in the 3D conformal scenario (67% TCP with MDE; 84% TCP without MDE) than for stereotactic radiotherapy (91% TCP with MDE; 100% TCP without MDE). Accordingly, an increase of the CTV margin had the greatest impact for the 3D conformal technique. Larger setup errors, with appropriate PTV margins, lead to an increase in TCP for both techniques, showing the interdependence of CTV and PTV margins. MDE may not always be eradicated by the beam penumbra or existing PTV margins using either 3D conformal or stereotactic radiotherapy. Nonetheless, TCP modeling indicates an overall local control rate above 90% for the stereotactic technique, while a non-zero CTV margin is recommended for better local control of MDE when using the 3D conformal technique.
    Radiotherapy and Oncology 09/2011; 100(3):344-50. · 4.52 Impact Factor
  • D De Ruysscher, B Reymen, A Van Baardwijk
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    ABSTRACT: The observation that improved local tumour control also results in increased survival rates, even in a disease such as non-small cell lung cancer (NSCLC), has fuelled the interest in strategies aimed at local tumour eradication. It has been demonstrated that a clear dose-response relationship exists for radiotherapy, i.e. higher doses of radiation lead to increased local tumour control. However, prolongation of the overall treatment time beyond 4-5 weeks renders radiotherapy less effective because of increased proliferation of tumour cells. It is therefore of interest to deliver as high doses as possible in short overall treatment times. An extreme example of this strategy is stereotactic body radiotherapy (SBRT), where a few large radiation doses, equalling very high biological doses, delivered in a short overall treatment time has resulted in at least 90 % tumour control in stage I NSCLC. However, when large volumes or critical normal structures such as the main bronchi are in the high-dose radiation volumes, more extensive fractionation schedules have been used, such as 70 Gy in 35 daily fractions of 2 Gy. As the overall treatment time than exceeds 4-5 weeks, hyperfractionated radiotherapy schedules have been introduced, which all delivered 2-3 relatively small fractions per day to total doses that are similar to the so-called standard regimen. Several randomized phase III trials and a meta-analysis based on individual patient data have demonstrated a superior 5-year survival with this strategy, without increased side effects. Our group has also shown that individualised hyperfractionated accelerated radiotherapy (INDAR) makes treatment with curative intent even in patients with large tumour volumes possible with few important side effects. Early results of INDAR with concurrent chemotherapy or with cetuximab are promising.
    Minerva chirurgica 08/2011; 66(4):341-5. · 0.39 Impact Factor
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    ABSTRACT: A pre-operative CT scan with contrast enhancement (CE) has recently been proposed to improve tumorbed delineation in breast conserving therapy. However, it is not clear whether CE is required for visualization of a known breast tumor. The main aims of this study were to compare the sensitivity of a CE-CT scan with a native CT scan (i.e. without CE) and to identify characteristics predictive for the requirement of CE. Both a CE-CT and a native CT were made in 58 breast cancer patients (age 37-75 yr), prior to breast conserving surgery. Visibility of the tumor on CT was scored by three observers (clearly visible/doubtful/not visible). Age, tumor size, palpable tumor yes/no, histology, and visibility on mammography were analyzed with respect to the visibility of the tumor on the native CT. The sensitivity for tumor detection was better for CE-CT (95%) than for native CT (83%) (p<0.001). Only mammographic visibility scores appeared to be significantly correlated with the visibility of the tumor on the native CT (p=0.013). In most patients CE is not required to visualize a known breast tumor. Mammographic visibility is a good parameter to decide on the use of CE.
    Radiotherapy and Oncology 07/2011; 100(2):271-5. · 4.52 Impact Factor
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    ABSTRACT: There is little data on the survival of elderly patients with stage III non-small cell lung cancer (NSCLC). Patients with stage III NSCLC in the Netherlands Cancer Registry/Limburg from January 1, 2002 to December 31, 2008 were included. One thousand and two patients with stage III were diagnosed, of which 237 were 75 years or older. From 228 patients, co-morbidity scores were available. Only 33/237 patients (14.5%) had no co-morbidities, 195 (85.5%) had one or more important co-morbidities, 60 (26.3%) two or more co-morbidities, 18 (7.9%) three or more co-morbidities and 2 patients (0.9%) suffered from four co-morbidities. Forty-eight percent were treated with curative intent. No significant difference in Charlson co-morbidity, age or gender was found between patients receiving curative or palliative intent treatment. Treatment with curative intent was associated with increased overall survival (OS) compared to palliative treatment: median OS 14.2 months (9.6-18.7) versus 5.2 months (4.3-6.0), 2-year OS 35.5% versus 12.1%, for curative versus palliative treatment. Patients who received only radiotherapy with curative intent had a median OS of 11.1 months (95% confidence interval [95% CI] 6.4-15.8) and a 5-year OS of 20.3%; for sequential chemotherapy and radiotherapy, the median OS was 18.0 months (95% CI 12.2-23.7), with a 5-year OS of 14.9%. Only four patients received concurrent chemo-radiation. In this prospective series treating elderly patients with stage III NSCLC with curative intent was associated with significant 5-year survival rates.
    European journal of cancer (Oxford, England: 1990) 07/2011; 47(18):2691-7. · 4.12 Impact Factor

Publication Stats

1k Citations
231.34 Total Impact Points


  • 2005–2014
    • Maastro Clinic
      Maestricht, Limburg, Netherlands
  • 2007–2013
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
    • Catholic University of Louvain
      Walloon Region, Belgium
  • 2010–2011
    • Hospital Universitario de Salamanca
      Helmantica, Castille and León, Spain
  • 2006–2011
    • Maastricht University
      • • Radiologie
      • • Department of Radiotherapy
      • • GROW School for Oncology & Developmental Biology
      Maastricht, Provincie Limburg, Netherlands