Andrew Vincent

Netherlands Cancer Institute, Amsterdamo, North Holland, Netherlands

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Publications (73)337.21 Total impact

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    ABSTRACT: Vulvar squamous cell carcinoma (VSCC) is treated with wide local excision. The challenge is to remove as much skin as necessary to prevent recurrence, but meanwhile preserve genital skin to diminish morbidity. Optical coherence tomography (OCT) is a noninvasive imaging tool that produces cross-sectional images. Optical coherence tomography could be helpful in determining appropriate surgical margins during excision of VSCC.
    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 10/2014;
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    ABSTRACT: Both preclinical and clinical data suggest that activation of the PI3K/AKT/mTOR pathway in response to hormonal therapy results in acquired endocrine therapy resistance. We evaluated differences in activation of the PI3K/AKT/mTOR pathway in estrogen receptor α (ERα) positive primary and corresponding metastatic breast cancer tissues using immunohistochemistry for downstream activated proteins, like phosphorylated mTOR (p-mTOR), phosphorylated 4E Binding Protein 1 (p-4EBP1) and phosphorylated p70S6K (p-p70S6K). For p-mTOR and p-4EBP1, the proportion of immunostained tumor cells (0-100%) was scored. Cytoplasmic intensity (0-3) was assessed for p-p70S6K. The difference between expression of these activated PI3K/AKT/mTOR proteins- in primary and metastatic tumor was calculated and tested for an association with adjuvant endocrine therapy. In patients who had received endocrine therapy (N=34), p-mTOR expression increased in metastatic tumor lesions compared to the primary tumor (median difference 45%), while in patients who had not received adjuvant endocrine therapy (N=37), no difference was found. Similar results were observed for p-4EBP1 and p-p70S6K expression. In multivariate analyses, adjuvant endocrine therapy was significantly associated with an increase in p-mTOR (p=0.01), p-4EBP1 (p=0.03) and p-p70S6K (p=0.001), indicating that compensatory activation of the PI3K/AKT/mTOR pathway might indeed be a clinically relevant resistance mechanism resulting in acquired endocrine therapy resistance. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 02/2014; · 6.20 Impact Factor
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    ABSTRACT: Inhibitors of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycine (PI3K/AKT/mTOR) pathway can overcome endocrine resistance in estrogen receptor (ER) alpha-positive breast cancer, but companion diagnostics indicating PI3K/AKT/mTOR activation and consequently endocrine resistance are lacking. PIK3CA mutations frequently occur in ERalpha-positive breast cancer and result in PI3K/AKT/mTOR activation in vitro. Nevertheless, the prognostic and treatment predictive value of these mutations in ERalpha-positive breast cancer is contradictive. We tested the clinical validity of PIK3CA mutations and other canonical pathway drivers to predict intrinsic resistance to adjuvant tamoxifen. In addition we tested the association between these drivers and downstream activated proteins METHODS: Primary tumors from 563 ERalpha-positive postmenopausal patients, randomized between adjuvant tamoxifen (1-3 years) versus observation were recollected. PIK3CA hotspot mutations in exon 9 and exon 20 were assessed with Sequenom Mass Spectometry. Immunohistochemistry was performed for human epidermal growth factor receptor 2 (HER2), phosphatase and tensin homolog (PTEN) and insulin-like growth factor 1 receptor (IGF-1R). We tested the association between these molecular alterations and downstream activated proteins (like phospho-protein kinase B (p-AKT), phospho-mammalian target of rapamycine (p-mTOR), p-ERK1/2 and p-p70S6K). Recurrence free interval improvement with tamoxifen versus control was assessed according to the presence or absence of canonical pathway drivers, using Cox proportional hazard models including a test for interaction. PIK3CA mutations (both exon 9 and exon 20) were associated with low tumor grade. An enrichment of PIK3CA exon 20 mutations was observed in progesterone receptor positive tumors. PIK3CA exon 20 mutations were not associated with downstream-activated proteins. No significant interaction between PIK3CA mutations or any of the other canonical pathway drivers and tamoxifen treatment benefit was found. PIK3CA mutations do not have clinical validity to predict intrinsic resistance to adjuvant tamoxifen and may therefore be unsuitable as companion diagnostic for PI3K/AKT/mTOR inhibitors in ERalpha- positive, postmenopausal, early breast cancer patients.
    Breast cancer research: BCR 01/2014; 16(1):R13. · 5.87 Impact Factor
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    ABSTRACT: Activation of the phosphatidylinositol-3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathways results in anti-estrogen resistance in vitro, but a biomarker with clinical validity to predict intrinsic resistance has not been identified. In metastatic breast cancer patients with previous exposure to endocrine therapy, the addition of a mammalian target of rapamycine (mTOR) inhibitor has been shown to be beneficial. Whether or not patients on adjuvant endocrine treatment might benefit from these drugs is currently unclear. A biomarker that predicts intrinsic resistance could potentially be used as companion diagnostic in this setting. We tested the clinical validity of different downstream-activated proteins in the PI3K and/or MAPK pathways to predict intrinsic tamoxifen resistance in postmenopausal primary breast cancer patients. We recollected primary tumor tissue from patients who participated in a randomized trial of adjuvant tamoxifen (1-3 years) versus observation. After constructing a tissue micro-array, cores from 563 estrogen receptor alpha positive were immunostained for p-AKT(Thr308), p-AKT(Ser473), p-mTOR, p-p706SK and p-ERK1/2. Cox proportional hazard models for recurrence free interval were used to assess hazard ratios and interactions between these markers and tamoxifen treatment efficacy. Interactions were identified between tamoxifen and p-AKT(Thr308), p-mTOR, p-p70S6K and p-ERK1/2. Applying a conservative level of significance, p-p70S6K remained significantly associated with tamoxifen resistance. Patients with p-p70S6K negative tumors derived significant benefit from tamoxifen (HR 0.24, P < 0.0001), while patients whose tumor did express p-p70S6K did not (HR = 1.02, P =0.95), P for interaction 0.004. In systemically untreated breast cancer patients, p-p70S6K was associated with a decreased risk for recurrence. Patients whose tumor expresses p-p70S6K, as a marker of downstream PI3K and/or MAPK pathway activation, have a favorable prognosis, but do not benefit from adjuvant tamoxifen. A potential benefit from inhibitors of the PI3K/Akt/mTOR pathway in these patients needs to be further explored.
    Breast cancer research: BCR 01/2014; 16(1):R6. · 5.87 Impact Factor
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    ABSTRACT: Ovarian cancer is the leading cause of death in women with gynecologic cancer. CA125 is the commonly used biomarker in the diagnosis of ovarian cancer, but has limitations in both sensitivity and specificity. Human Epididymal secretory protein (HE4) is a promising biomarker and is included in the Risk of Ovarian Malignancy Algorithm (ROMA) score, which is suggested to further increase the diagnostic accuracy than either marker alone. However, information from ultrasound and CT-scan is not included in this algorithm. This study evaluated the diagnostic accuracy of HE4 in the pre-operative diagnosis of ovarian cancer and the predictive values of biomarkers, ultrasound and CT-scan and combinations hereof. HE4 and CA125 were measured in 361 subjects (34 benign, 147 ovarian cancer and 180 controls). Sensitivity, specificity and area under the curve (AUC) for CA125, HE4, ROMA and RMI scores were calculated using the receiver operating characteristic (ROC) methodology. The additional predictive value of ultrasound or CT-scan to the individual markers was analyzed using logistic regression. The sensitivity in predicting ovarian cancer of CA125 was 91% and of HE4 90%. The specificity was 65% and 97% respectively. HE4 demonstrated the highest discrimination (ROC-AUC=0.96), compared to ROMA, RMI and CA125 (AUC=0.95, 0.89 and 0.90 respectively). ROMA did not improve when it was combined with different ultrasound factors. The presence of intra-abdominal metastasis on CT-scan improved the discriminative potential of HE4 (p=0.0004). HE4 in combination with CT-scan may be incorporated in the diagnostic work-up in women with a pelvic mass.
    Gynecologic Oncology 01/2014; · 3.93 Impact Factor
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    ABSTRACT: This study examined the incidence and risk factors of surgical wound complications after inguinal lymph node dissection in melanoma patients. Overall complication rate was 72%. Older age was confirmed as a risk factor, but other risk factors could not be established with certainty.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 01/2014; · 2.56 Impact Factor
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    ABSTRACT: Background After preoperative chemoradiotherapy (CRT) for rectal cancer, clinically undetectable residual tumour deposits or pathologic lymph nodes may remain in the mesorectum. Aim The aim of this study was to report histopathological effects of CRT and factors affecting outcome in a uniformly treated series of locally advanced rectal cancer (LARC) patients. Methods Between 2004 and 2008, 107 patients with cT3 (threatening the mesorectal fascia or <5 cm from the anal verge), cT4 or cN2 rectal cancer were treated with preoperative CRT (25 × 2 Gy with capecitabine) and TME 6–8 weeks later. Central histopathological review followed. Tumour regression grade (TRG) was scored in pCR, near-pCR, response and no response. Cox regression was performed to identify prognosticators. Results The 3-year distant metastasis-free interval, disease-free rate and overall survival rate were 82%, 73% and 87% (median 44 months follow-up). TRG consisted of 20% pCR, 11% near-pCR, 55% response and 14% no response. 6/21 pCR patients harboured nodal metastases. 5/12 near-pCR had ypT3 disease, while 6 harboured node metastases. 5/12 near-PCR patients developed distant metastases. ypN and TRG were powerful outcome discriminators. Conclusion The high number of near-pCR with ypT3 or ypN1/2 and their poor outcome demonstrates that “watch-and-wait” in LARC patients should be applied with care.
    Radiotherapy and Oncology. 01/2014;
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    ABSTRACT: Tamoxifen has dramatically reduced the recurrence and mortality rate of estrogen receptor positive breast cancer. However, the efficacy of tamoxifen varies between individuals and 40% of patients will have a recurrence despite adjuvant tamoxifen treatment. Factors that predict tamoxifen efficacy would be helpful for optimizing treatment. Serum concentrations of the active metabolite, endoxifen, may be positively related to treatment outcome. In addition, hot flashes are suggested to be positively associated with tamoxifen treatment outcome. We investigated in a series of 109 patients whether the frequency and severity of hot flashes were related to concentrations of tamoxifen and its metabolites. A serum sample of all patients was analyzed for the concentration of tamoxifen, N-desmethyltamoxifen, endoxifen and 4-hydroxytamoxifen, as well as for estradiol concentrations and several single nucleotide polymorphisms in CYP2D6. Additionally, these patients completed a questionnaire concerning biometric data and treatment side effects. We found no evidence supporting an association between concentrations of tamoxifen or metabolites and either the frequency or severity of hot flashes in the covariate unadjusted analyses. However, including interactions with menopausal status and pre-treatment hot flash (PTHF) history indicated that post-menopausal women with PTHF experienced an increasing frequency of hot flashes with increasing serum concentrations of tamoxifen and its metabolites. This finding was not altered when adjusting for potential confounding factors (duration of tamoxifen treatment, CYP2D6 phenotype, estradiol serum concentration, age and body mass index). In addition we observed a positive association between body mass index and both hot flash frequency (p = 0.04) and severity (p < 0.0001). We also observed that patients with lower estradiol levels reported more severe hot flashes (p = 0.02). No univariate associations were observed between concentrations of active tamoxifen metabolites and either the frequency or severity of hot flashes during treatment. However, the frequency of hot flashes may be exacerbated by higher serum concentrations of tamoxifen and its metabolites in post-menopausal women with a history of hot flashes prior to tamoxifen treatment.
    BMC Cancer 12/2013; 13(1):612. · 3.33 Impact Factor
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    ABSTRACT: Breathing through a tracheostoma results in insufficient warming and humidification of the inspired air. This loss of air-conditioning, especially humidification, can be partially restored with the application of a Heat and Moisture Exchanger (HME) over the tracheostoma. For medical professionals it is not easy to judge differences in water exchange performance of various HMEs due to the lack of universal outcome measures. This study has three aims: assessment of the water exchange performance of commercially available HMEs for laryngectomized patients, validation of these results with absolute humidity outcomes, and assessment of the role of hygroscopic salt present in some of the tested HMEs. Measurements of weight and absolute humidity at end-inspiration and end-expiration at different breathing volumes of a healthy volunteer were performed using a microbalance and humidity sensor. Twenty-three HMEs of six different manufacturers were tested. Associations were determined between core weight, weight change, breathing volume, and absolute humidity, using both linear and non-linear mixed effects models. Water exchange of the 23 HMEs at a breathing volume of 0.5 liter varies between 0.5-3.6 mg. Both water exchange and wet core weight correlate strongly with the end-inspiratory absolute humidity values (R(2)=0.89 / 0.87). Hygroscopic salt increases core weight. The 23 tested HMEs for laryngectomized patients show wide variation in water exchange performance. Water exchange correlates well with the end-inspiratory absolute humidity outcome, which validates the ex vivo weight change method. Wet core weight is a predictor of HME performance. Hygroscopic salt increases the weight of the core material. The results of this study can help medical professionals to obtain a more founded opinion about the performance of available HMEs for pulmonary rehabilitation in laryngectomized patients, and uniquely allow them to make an informed decision on which of HME type to use.
    Respiratory care. 11/2013;
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    ABSTRACT: Modest benefits from concurrent chemoradiotherapy in patients with locally advanced NSCLC warrant further clinical investigations to identify more effective treatment regimens. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. We report on the safety and efficacy of the combination of daily dose Cisplatin and concurrent radiotherapy with or without weekly Cetuximab. Patients received high dose accelerated radiotherapy (66Gy in 24 fractions) and concurrent daily Cisplatin (6mg/m(2)) without (Arm A) or with (Arm B) weekly Cetuximab (400mg/m(2) loading dose one week prior to radiotherapy followed by weekly 250mg/m(2)). The primary endpoint of the trial was objective local control rate (OLCR) determined at 6-8weeks after treatment. Toxicity was reported as well. Between February 2009 and May 2011, 102 patients were randomized. Median follow up was 29months. The OLCR was 84% in Arm A and 92% in Arm B (p=0.36). The one-year local progression free interval (LPFI) and overall survival (OS) were 69% and 82% for Arm A and 73% and 71% for Arm B, respectively (LPFI p=0.39; OS p=0.99). Toxicity compared equally between both groups. The addition of Cetuximab to radiotherapy and concurrent Cisplatin did not improve disease control in patients with locally advanced NSCLC but increased treatment related toxicity.
    Radiotherapy and Oncology 11/2013; · 4.52 Impact Factor
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    ABSTRACT: To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account. In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis. A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively. In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR.
    European Journal of Nuclear Medicine 08/2013; · 4.53 Impact Factor
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    ABSTRACT: Dyspnea is the most common symptom in patients with malignant pleural effusion (MPE). Treatment decisions are primarily based on the perception of dyspnea severity. To study dyspnea perception following therapeutic thoracentesis using the visual analog scale (VAS) dyspnea score and modified Borg scale (MBS). To investigate whether patient reported outcome (PRO) measures can predict pleural re-interventions. Consecutive patients presenting with symptomatic MPE and planned for therapeutic thoracentesis were asked to complete MBS and VAS dyspnea scores (both at rest and during exercise) daily for 14 consecutive days. Physicians, unaware of the results of these PRO measures, decided on the necessity of a re-intervention, according to routine care. PRO measures were analyzed and correlated with performed re-interventions and the volume of removed fluid. Forty-nine out of 64 consecutive patients returned the diaries. Twenty-eight patients (57 %) had a re-intervention within 30 days. Patients who required a re-intervention reported significantly higher MBS than patients who did not. The extent of increase in MBS during exercise was related to the need for re-intervention. Regarding the MBS during exercise, median time to maximal relief was 2 days. Re-intervention was required sooner when larger volumes were drained. Patient reported outcomes are useful tools to assess treatment effect of therapeutic thoracentesis. Median time to maximal relief is 2 days. MBS rather than VAS dyspnea score appears to be more prognostic for repeat pleural drainage within 30 days.
    Supportive Care in Cancer 07/2013; · 2.09 Impact Factor
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    ABSTRACT: Malignant pleural effusion is a common complication in end-stage cancer patients and can cause severe dyspnea. Therapeutic thoracentesis is often limited to 1 to 1.5 L. Pleural manometry can be used to recognize a not-expanded lung. Interval pleural pressure measurements with a high temporal resolution were performed after each removal of 200 mL of fluid to observe pleural pressure swings. Pleural elastance was defined as the difference in pleural pressure divided by the change in volume. Chest x-rays were performed to evaluate lung expansion, reexpansion pulmonary edema, and fluid residue. Thirty-four procedures in 30 patients were eligible for analysis. Four patients had incomplete lung expansion after drainage. No reexpansion pulmonary edema was observed. Pleural pressure swing after 200 mL drainage was higher when the lung did not expand. Pleural elastance after removal of 500 mL was higher in the not-expanded subgroup. We demonstrated that a high pleural pressure swing after removal of only 200 mL was related to incomplete lung expansion. We confirmed the association between pleural elastance and lung expansion.
    Journal of bronchology & interventional pulmonology. 07/2013; 20(3):200-5.
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    ABSTRACT: BACKGROUND: We investigated whether genomic aberrations in primary colorectal cancer (CRC) can identify patients who are at increased risk of developing additional hepatic recurrence after colorectal liver metastases (CLM) resection. METHODS: Primary tumour DNA from 79 CLM resected patients was analysed for recurrent copy number changes (12x135k NimbleGen(™) aCGH). The cohort was divided into three groups: CLM patients with a recurrence-free survival after hepatic resection of at least 5 years (n = 21), patients who developed intra-hepatic recurrence (n = 32), and patients who developed extrahepatic recurrence (n = 26). By contrasting the primary tumour profiles of recurrence free and the extrahepatic recurrence CLM patients, a classifier, the extra-hepatic recurrence classifier (ERC1), predictive for subsequent extrahepatic-recurrence was developed. RESULTS: The ERC1 had an accuracy of 70 % (95 % confidence interval (CI): 55-82 %, misclassification error 30 %, base error rate: 45 %). This analysis identified a region on Chromosome 12p13 as differentially aberrated between these two groups. The classifier was further optimized by contrasting the extrahepatic recurrence group with the combined group of intrahepatic and no recurrence group, resulting in an extrahepatic prognostic classifier (ERC2) able to classify patients with CLMs suitable for hepatic resection with 74 % accuracy (95 % CI: 62-83 %, misclassification error 26 %, base error rate: 32 %). CONCLUSIONS: Patients with CLM who will develop extrahepatic recurrence may be identified with ERCs based on information in the primary tumour. Risk estimates for the occurrence of extrahepatic metastases may allow a reduction of hepatic resections of colorectal liver metastases for those who are unlikely to develop extrahepatic metastases.
    Annals of Surgical Oncology 06/2013; · 4.12 Impact Factor
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    ABSTRACT: Estrogen catabolism is a major function of CYP2C19. The effect of CYP2C19 polymorphisms on tamoxifen sensitivity may therefore not only be mediated by a variation in tamoxifen metabolite levels but also by an effect on breast cancer risk and molecular subtype due to variation in lifelong exposure to estrogens. We determined the association between these polymorphisms and tamoxifen sensitivity in the context of a randomized trial, which allows for the discernment of prognosis from prediction. We isolated primary tumor DNA from 535 estrogen receptor-positive, stages I-III, postmenopausal breast cancer patients who had been randomized to tamoxifen (1-3 years) or no adjuvant therapy. Recurrence-free interval improvement with tamoxifen versus control was assessed according to the presence or absence of CYP2C19*2 and CYP2C19*17. Hazard ratios and interaction terms were calculated using multivariate Cox proportional hazard models, stratified for nodal status. Tamoxifen benefit was not significantly affected by CYP2C19*17. Patients with at least one CYP2C19*2 allele derived significantly more benefit from tamoxifen (HR 0.26; p = 0.001) than patients without a CYP2C19*2 allele (HR 0.68; p = 0.18) (p for interaction 0.04). In control patients, CYP2C19*2 was an adverse prognostic factor. In conclusion, breast cancer patients carrying at least one CYP2C19*2 allele have an adverse prognosis in the absence of adjuvant systemic treatment, which can be substantially improved by adjuvant tamoxifen treatment.
    Breast Cancer Research and Treatment 06/2013; · 4.47 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: The aim of this study was to correlate clinical and dosimetric variables with acute esophageal toxicity (AET) following Intensity Modulated Radiotherapy (IMRT) with concurrent chemotherapy for locally advanced non-small cell lung cancer (NSCLC). In addition, timeline of AET was reported. MATERIAL AND METHODS: 153 patients with locally advanced NSCLC treated with 66Gy/2.75Gy/24 fractions of radiotherapy and concurrent daily low dose cisplatin were selected. Medical records and treatments of these patients were retrospectively reviewed. Maximum AET grade ⩾2 and maximum grade 3 were the endpoints of this study. Dates for onset, maximum and recovery (to baseline) of AET were reported. Univariate and multivariate analysis were applied to correlate clinical, tumor, dosimetric and chemotherapy dose variables to AET grade ⩾2 and grade 3. RESULTS: AET grade 2 occurred in 37% and grade 3 in 20% of the patients. The median onset of AET was around day 15 for all grades. The median onset of the maximum grade was day 30 for both grades 2 and 3. The median duration was 43days for grade 1, 50days for grade 2 and >80days for grade 3. Of the grade 3 AET patients, 48% recovered within 3months. Esophagus V50, ethnic background, and the number of cisplatin administrations were significantly correlated with grade 3 AET. CONCLUSIONS: For NSCLC patients treated with concurrent chemotherapy and IMRT A higher number of cisplatin administrations, non-Caucasian background and higher V50oes were associated with grade 3 AET. The median onset of AET grade 3 is 15days after the start of treatment, maximized at day 30, with a median duration of >80days.
    Radiotherapy and Oncology 05/2013; · 4.52 Impact Factor
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    ABSTRACT: Laryngectomized patients suffer from respiratory complaints due to insufficient warming and humidification of inspired air in the upper respiratory tract. Improvement of pulmonary humidification with significant reduction of pulmonary complaints is achieved by the application of a heat and moisture exchanger (HME) over the tracheostoma. The aim of this study was to determine whether the new Provox HMEs (XM-HME and XF-HME) have a better water exchange performance than their predecessors (R-HME and L-HME, respectively; Atos Medical, Hörby, Sweden). The other aim was to assess the short-term clinical feasibility of these HMEs. The XM-HME and XF-HME were weighed at the end of inspiration and at the end of expiration at different breathing volumes produced by a healthy volunteer. The associations between weight changes, breathing volume and absolute humidity were determined using both linear and non-linear mixed effects models. Study-specific questionnaires and tally sheets were used in the clinical feasibility study. The weight change of the XM-HME is 3.6 mg, this is significantly higher than that of the R-HME (2.0 mg). The weight change of the XF-HME (2.0 mg) was not significantly higher than that of the L-HME (1.8 mg). The absolute humidity values of both XM- and XF-HME were significantly higher than that of their predecessors. The clinical feasibility study did not reveal any practical problems over the course of 3 weeks. The XM-HME has a significantly better water exchange performance than its predecessor (R-HME). Both newly designed HMEs did succeed in the clinical feasibility study.
    Archives of Oto-Rhino-Laryngology 05/2013; · 1.29 Impact Factor
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    ABSTRACT: BACKGROUND: Standard chemotherapy does not lead to long-term survival in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma is strongly dependent on vasculature with high vessel counts and high concentrations of serum vascular growth factors. Thalidomide has shown antiangiogenic activity, and we hypothesised that its use in the maintenance setting could improve outcomes. METHODS: In this open-label, multicentre, randomised phase 3 study, eligible patients had proven malignant pleural or peritoneal mesothelioma and had received a minimum of four cycles of first-line treatment containing at least pemetrexed, with or without cisplatin or carboplatin, and had not progressed on this treatment. Patients were randomly assigned (in a 1:1 ratio, stratified by previous first-line chemotherapy, histological subtype, and recruiting hospital) to receive thalidomide 200 mg per day (including a 2 week run in of 100 mg per day) plus active supportive care or active supportive care alone until disease progression. Patients were required to be registered and to start treatment with thalidomide within 10 weeks after the end of the first-line chemotherapy. Thalidomide was given for a maximum of 1 year or until unacceptable toxicity. The primary endpoint was time to progression. The primary analyses were by intention to treat. The study is registered, ISRCTN13632914. FINDINGS: Between May 11, 2004, and Dec 23, 2009, we randomly assigned 222 patients, 111 in each group (one patient on active supportive care later withdrew consent and was excluded from analyses). At the time of this final analysis, median follow-up was 33·1 months (IQR 22·3-66·8), and physician-reported disease progression had occurred in 104 patients in the thalidomide group and 107 in the active supportive care group; 92 patients in the thalidomide group and 93 in the active supportive care group had died. Median time to progression in the thalidomide group was 3·6 months (95% CI 3·2-4·1) compared with 3·5 months (2·3-4·8) in the active supportive care group (hazard ratio 0·95, 95% CI 0·73-1·20, p=0·72). 43 (39%) grade 3 or 4 adverse events were reported in the thalidomide group and 31 (28%) in the active supportive care group; neurosensory events were reported by two (2%) patients on thalidomide and none on active supportive care, cardiac events by two (2%) patients on thalidomide and three (3%) on active supportive care, and thromboembolic events by three (3%) patients on thalidomide and none on active supportive care. INTERPRETATION: No benefit was noted in time to progression with the addition of thalidomide maintenance to first-line chemotherapy. Different treatment strategies are needed to improve outcomes in patients with malignant mesothelioma. FUNDING: Dutch Cancer Society (KWF), Eli Lilly, NSW Dust Disease Compensation Board, University of Sydney, and Cancer Australia.
    The Lancet Oncology 04/2013; · 25.12 Impact Factor
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    ABSTRACT: Background:Breathing through a tracheostomy results in insufficient warming and humidification of inspired air. This loss of air-conditioning can be partially compensated for with the application of a Heat and Moisture Exchanger (HME) over the tracheostomy. In vitro (ISO 9360-2:2001) and in vivo measurements of the effects of an HME are complex and technically challenging. Aim of this study is to develop a simple method to measure the ex vivo HME performance comparable with previous in vitro and in vivo results.Materials and methods:HMEs are weighed at the end of inspiration and at the end of expiration at different breathing volumes. Four HMEs (Atos Medical, Hörby, Sweden) with known in vivo humidity and in vitro water loss values were tested. The associations between weight change, volume and absolute humidity were determined using both linear and non-linear mixed effects models.Results:The rating between the four HMEs by weighing correlates with previous intra-tracheal measurements (R2 = 0.98), and the ISO-standards (R2 = 0.77).Conclusion:Assessment of the weight change between end of inhalation and end of exhalation is a valid and simple method of measuring the water exchange performance of an HME.
    Respiratory care 03/2013; · 2.03 Impact Factor
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    ABSTRACT: BACKGROUND: Complication rates after inguinal lymph node dissection (ILND) are high. Risk factors for early wound complications after ILND in patients with penile carcinoma have not yet been studied. OBJECTIVES: To assess the frequency of early wound complications in a contemporary series and to identify clinical risk factors for early wound complications after ILND for penile carcinoma. DESIGN, SETTING, AND PARTICIPANTS: We evaluated 237 ILNDs in 163 patients with penile cancer treated between 2003 and 2012 at the Netherlands Cancer Institute. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the occurrence of wound infection, skin-flap problems, and seroma formation and graded complications using the modified Clavien system. Univariable and multivariable penalised mixed effects logistic regression was used to identify clinical risk factors for occurrence of any complication (grade ≥1) and of moderate to severe complications (grade ≥2). RESULTS AND LIMITATIONS: One complication or more occurred in 58% of the procedures, and 10% of those complications were severe. Wound infection occurred in 43%, seroma formation occurred in 24%, and skin-flap problems occurred in 16%. Palpable disease was the only factor associated with grade ≥1 complications in the univariable analysis (odds ratio [OR]: 0.43; p=0.02). In the multivariable model, after penalisation, no statistically significant risk factors remained. Univariable associations for grade ≥2 complications were present for body mass index (BMI; OR of 1.66 for a 5.8-point change in BMI; p=0.05) and sartorius muscle transposition (OR: 2.64; p=0.04). In the reduced multivariable model, the OR for sartorius muscle transposition was 2.12 (p=0.06) and for BMI was 1.76 (p=0.03). In addition, bilateral dissection approached significance in the multivariable model (OR: 2.17; p=0.06). This study is limited by its observational nature. CONCLUSIONS: Wound complication rates after ILND are high in this cohort. BMI, sartorius muscle transposition, and bilateral dissection were the factors most strongly associated with the occurrence of grade ≥2 wound complications.
    European Urology 03/2013; · 10.48 Impact Factor

Publication Stats

552 Citations
337.21 Total Impact Points

Institutions

  • 2007–2014
    • Netherlands Cancer Institute
      • • Department of Biometrics
      • • Department of Medical Oncology
      • • Department of Head and neck Oncology / Surgery
      Amsterdamo, North Holland, Netherlands
  • 2011
    • Kantonsspital St. Gallen
      San Gallo, Saint Gallen, Switzerland
  • 2006–2010
    • VU University Medical Center
      • Department of Radiation Oncology
      Amsterdam, North Holland, Netherlands
  • 2008
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdam, North Holland, Netherlands