Amsterdam, Netherlands
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Kruijff S.,University of Groningen | Bastiaannet E.,Leiden University | Francken A.B.,Isala Clinics | Schaapveld M.,NKI AvL | And 2 more authors.
British Journal of Cancer | Year: 2012

Background: Melanoma incidence has increased rapidly in the last decades, and predictions show a continuing increase in the years to come. The aim of this study was to assess trends in melanoma incidence, Breslow thickness (BT), and melanoma survival among young and elderly patients in the Netherlands.Methods: Patients diagnosed with invasive melanoma between 1994 and 2008 were selected from the Netherlands Cancer Registry. Incidence (per 100 000) over time was calculated for young (≥ 65 years) and elderly patients (≥ 65 years). Distribution of BT for young and elderly males and females was assessed. Regression analysis of the log-transformed BT was used to assess changes over time. Relative survival was calculated as the ratio of observed survival to expected survival.Results:Overall, 40 880 patients were included (42.3% male and 57.7% female). Melanoma incidence increased more rapidly among the elderly (5.4% estimated annual percentage change (EAPC), P<0.0001) than among younger patients (3.9% EAPC, P<0.0001). The overall BT declined significantly over time (P<0.001). Among younger patients, BT decreased for almost all locations. Among elderly males, BT decreased for melanomas in the head and neck region (P<0.001) and trunk (P<0.001), but did not decrease significantly for the other regions. Among elderly females, BT only decreased for melanomas at the trunk (P<0.01). The relative survival of elderly patients was worse compared with that of younger patients (P<0.001).Conclusion:Melanoma incidence increases more rapidly for elderly than for younger patients and the decline in BT is less prominent among elderly patients than among young patients. Campaigns in the Netherlands should focus more on early melanoma detection in the elderly. © 2012 Cancer Research UK All rights reserved.


PubMed | AMC UvA, University of Twente and NKI AVL
Type: Journal Article | Journal: Urology annals | Year: 2015

Currently, (multiple) biopsies are taken to obtain histopathological diagnosis of suspicious lesions of the penile skin. Optical coherence tomography (OCT) provides noninvasive in vivo images from which epidermal layer thickness and attenuation coefficient (oct) can be quantified. We hypothesize that qualitative (image assessment) and quantitative (epidermal layer thickness and attenuation coefficient, oct) analysis of penile skin with OCT is possible and may differentiate benign penile tissue from (pre) malignant penile tissue.Optical coherence tomography-imaging was performed prior to punch biopsy in 18 consecutive patients with a suspicious lesion at the outpatient clinic of the NKI-AVL. Qualitative analysis consisted of visual assessment of clear layers and a visible lower border of the lesions, quantitative analysis comprised of determination of the epidermal layer thickness and oct. Results were grouped according to histopathology reports.Qualitative analysis showed a statistically significant difference (P = 0.047) between benign and (pre) malignant lesions. Quantitative analysis showed that epidermal layer thickness and attenuation coefficient was significantly different between benign and (pre) malignant tissue, respectively, P = 0.001 and P < 0.001.In this preliminary study, qualitative and quantitative analysis of OCT-images of suspicious penile lesions shows differences between benign lesions and (pre) malignant lesions. These results encourage further research in a larger study population.


PubMed | EORTC Headquarters, Gelre Hospital, Nij Smellinghe Hospital, European Organisation for Research and Treatment of Cancer and 8 more.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

LBA1001 Background: Sentinel node biopsy (SNB) is standard in assessing axillary lymph node status for cN0 breast cancer patients. In case of a positive SNB, if treatment is advised, axillary lymph node dissection (ALND) is the current standard. Although ALND provides excellent regional control, it may give harmful side effects. Axillary radiotherapy (ART) instead of ALND was hypothesized to provide comparable regional control and less side effects.From 2001 to 2010, patients with cT1E2N0 primary breast cancer were enrolled in the EORTC phase III non-inferiority AMAROS trial. Patients were randomized between ALND and ART in case of a positive SNB. Primary endpoint was 5-year axillary recurrence rate. Secondary endpoints were overall survival (OS), disease-free survival (DFS), quality of life (QOL), shoulder movement and lymphedema at 1 and 5 years.Of the 4,806 patients entered in the trial, 744 in the ALND-arm and 681 in the ART-arm had a positive SNB, 60% with a macrometastasis. The two treatment-arms were comparable regarding age, tumor size, grade, tumor type, and adjuvant systemic treatment. With a median follow up of 6.1 years, the 5-year axillary recurrence rate after a positive SNB was 0.54% (4/744) after ALND versus 1.03% (7/681) after ART. The planned non-inferiority test was underpowered because of the unexpectedly low number of events. The axillary recurrence rate after a negative SNB was 0.8% (25/3131). There were no significant differences between treatment arms regarding OS (5 yr estimates: 93.27% ALND, 92.52% ART, p=0.3386) and DFS (5 yr estimates: 86.90% ALND, 82.65% ART, p=0.1788). Lymphedema was found significantly more often after ALND (1yr: 40% ALND, 22% ART, p<0.0001 and 5yr: 28% ALND, 14% ART, p<0.0001). There was a nonsignificant trend toward more early shoulder movement impairment after ART. These findings were compatible with a trend in two QOL items in the arm symptom scale: swelling (ART better) and movement (ALND better). There were no other differences in QOL.ALND and ART after a positive SNB provide excellent and comparable regional control. ART reduces the risk of short-term and long-term lymphedema compared to ALND.NCT00014612.


PubMed | University Utrecht, Max Delbrück Center for Molecular Medicine and NKI AVL
Type: Journal Article | Journal: Assay and drug development technologies | Year: 2016

High-content screening (HCS) can generate large multidimensional datasets and when aligned with the appropriate data mining tools, it can yield valuable insights into the mechanism of action of bioactive molecules. However, easy-to-use data mining tools are not widely available, with the result that these datasets are frequently underutilized. Here, we present HC StratoMineR, a web-based tool for high-content data analysis. It is a decision-supportive platform that guides even non-expert users through a high-content data analysis workflow. HC StratoMineR is built by using My Structured Query Language for storage and querying, PHP: Hypertext Preprocessor as the main programming language, and jQuery for additional user interface functionality. R is used for statistical calculations, logic and data visualizations. Furthermore, C++ and graphical processor unit power is diffusely embedded in R by using the rcpp and rpud libraries for operations that are computationally highly intensive. We show that we can use HC StratoMineR for the analysis of multivariate data from a high-content siRNA knock-down screen and a small-molecule screen. It can be used to rapidly filter out undesirable data; to select relevant data; and to perform quality control, data reduction, data exploration, morphological hit picking, and data clustering. Our results demonstrate that HC StratoMineR can be used to functionally categorize HCS hits and, thus, provide valuable information for hit prioritization.


Wessels R.,NKI AvL | De Bruin D.M.,AMC UvA | Relyveld G.N.,NKI AvL | Faber D.J.,AMC UvA | And 5 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2015

Background Cutaneous melanomas are diagnosed worldwide in 231 130 patients per year. The sensitivity and specificity of melanoma diagnosis expresses the need for an additional diagnostic method. Optical coherence tomography (OCT) has shown that it allows morphological (qualitative) description of image features and quantitative analysis of pathology related light scattering by means of the attenuation coefficient (μoct). Objective We hypothesize that OCT images of nevi will differ qualitatively and quantitatively from melanomas. Methods Forty lesions from 33 consecutive patients were imaged with OCT. After data acquisition, excision was performed. Epidermal layer thickness was measured and values of μoct were extracted from 200 OCT images of pigmented lesions. Results Morphologically, absence of the lower border of the lesion was characteristic for melanoma (P = 0.02). Also, the μoct was different between benign and malignant lesions (P = 0.02). There were no differences in epidermal layer thickness of benign lesions and melanoma. Conclusion Although this preliminary study comprised a small number of patients, quantitative analysis of OCT images in pigmented skin lesions give valuable additional information about lesions characteristics. When using the attenuation coefficient, it might be possible to distinguish between benign lesions and melanomas. © 2014 European Academy of Dermatology and Venereology.


Uyterlinde W.,NKI AVL | Chen C.,NKI AVL | Kwint M.,NKI AVL | De Bois J.,NKI AVL | And 4 more authors.
Radiotherapy and Oncology | Year: 2013

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 66 Gy/2.75 Gy/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 43 days for grade 1, 50 days for grade 2 and >80 days for grade 3. Of the grade 3 AET patients, 48% recovered within 3 months. 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 15 days after the start of treatment, maximized at day 30, with a median duration of >80 days. © 2013 Elsevier Ltd. All rights reserved.


PubMed | Gelderse Vallei Hospital, VU University Amsterdam and NKI AVL
Type: Journal Article | Journal: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology | Year: 2016

Neoadjuvant chemotherapy (NACT) is increasingly used in patients with operable disease due to the potential of converting patients requiring mastectomy to breast conserving surgery (BCS) or lowering resection volumes to improve cosmetic outcome. This nationwide retrospective study aims to determine margin status and specimen volume in patients with invasive breast cancer who underwent BCS after NACT.All patients who underwent BCS in 2012-2013 for invasive breast cancer were selected from a nationwide network and registry of histology and cytopathology in the Netherlands (PALGA).Of the 9901 patients, 626 (6.3%) received NACT. After primary surgery 949 (10.2%) patients had tumour-involved margins compared to 152 (24.3%) after NACT. Close margins (1mm) were seen in another 111 (17.7%) patients after NACT. The adjusted odds ratio for involved margins after NACT was 2.94, meaning a three times higher risk of involved margins compared with primary surgery. In patients with lobular carcinoma (54.9%) and no response to NACT (42.1%) higher tumour-involved margins were seen. High resection volumes >60cc were observed in 224 (36%) patients after NACT of which 37 (16.5%) had tumour involved margins and 32 (14.3%) close margins 1mm.The primary goal of the surgeon performing BCS after NACT, to reach tumour-free margins, is not accomplished in one out of four patients. Patients especially at risk are patients with ILC and no pathological tumour response. Excessive resection volumes after NACT do not guarantee tumour-free margins. Further research is necessary to analyze whether we are counterproductive when NACT is given in order to lower resection volumes.


PubMed | NKI AvL
Type: Journal Article | Journal: Journal of the European Academy of Dermatology and Venereology : JEADV | Year: 2015

Cutaneous melanomas are diagnosed worldwide in 231,130 patients per year. The sensitivity and specificity of melanoma diagnosis expresses the need for an additional diagnostic method. Optical coherence tomography (OCT) has shown that it allows morphological (qualitative) description of image features and quantitative analysis of pathology related light scattering by means of the attenuation coefficient (oct ).We hypothesize that OCT images of nevi will differ qualitatively and quantitatively from melanomas.Forty lesions from 33 consecutive patients were imaged with OCT. After data acquisition, excision was performed. Epidermal layer thickness was measured and values of oct were extracted from 200 OCT images of pigmented lesions.Morphologically, absence of the lower border of the lesion was characteristic for melanoma (P = 0.02). Also, the oct was different between benign and malignant lesions (P = 0.02). There were no differences in epidermal layer thickness of benign lesions and melanoma.Although this preliminary study comprised a small number of patients, quantitative analysis of OCT images in pigmented skin lesions give valuable additional information about lesions characteristics. When using the attenuation coefficient, it might be possible to distinguish between benign lesions and melanomas.


PubMed | Gelderse Vallei Hospital, VU University Amsterdam and NKI AVL
Type: | Journal: Breast (Edinburgh, Scotland) | Year: 2016

The current study aims to assess margin status in relation to amount of healthy breast tissue resected in breast-conserving surgery (BCS) on a nationwide scale.Using PALGA (a nationwide network and registry of histology and cytopathology in the Netherlands), all patients who underwent BCS for primary invasive carcinoma in 2012-13 were selected (10,058 excerpts). 9276 pathology excerpts were analyzed for a range of criteria including oncological margin status and distance to closest margin, specimen weight/volume, greatest tumor diameter, and with or without localization method. Calculated resection ratios (CRR) were assessed to determine excess healthy breast tissue resection.Margins for invasive carcinoma and in situ carcinoma combined were tumor-involved in 498 (5.4%) and focally involved in 1021 cases (11.0%) of cases. Unsatisfactory resections including (focally) involved margins and margins1mm were reported in 33.8% of patients. The median lumpectomy volume was 46cc (range 1-807cc; SD 49.18) and median CRR 2.32 (range 0.10-104.17; SD 3.23), indicating the excision of 2.3 the optimal resection volume.The unacceptable rate of tumor-involved margins as well as margins1mm in one third of all patients is also achieved at the expense of healthy breast tissue resection, which may carry the drawback of high rates of cosmetic failure. These data clearly suggest the need for improvement in current breast conserving surgical procedures to decrease tumor-involved margin rates while reducing the amount of healthy breast tissue resected.


PubMed | RTP Research Group and NKI AVL
Type: Evaluation Studies | Journal: Medical physics | Year: 2015

MRI guidance during radiotherapy has the potential to enable more accurate dose delivery, optimizing the balance between local control and treatment related toxicity. However, the presence of a permanent magnetic field influences the dose delivery, especially around air cavities. Here, electrons are able to return to the surface through which they entered the air cavity (electron return effect, ERE) locally resulting in dose hot- and cold-spots. Where RT of rectal cancer patients might benefit from MRI guidance for margin reduction, air cavities in and around the target volume are frequently present. The purpose of this research is to evaluate the impact of the presence of a 1.5 T transverse magnetic field on dose delivery in patients with rectal cancer.Ten patients treated with 5 5 Gy RT having large changes in pelvic air content were selected out of a cohort of 33 patients. On the planning CT, a 1.5 T, 6 MV, 7-field intensity modulated radiotherapy (IMRT) plan was created. This plan was subsequently recalculated on daily CT scans. For each daily CT, the CTV V95% and V107% and bowel area V(5Gy), V(10Gy), V(15Gy), V(20Gy), and V(25Gy) were calculated to evaluate the changes in dose distribution from fraction to fraction. For comparison, the authors repeated this procedure for the 0 T situation. To study the effect of changing air cavities separate from other anatomical changes, the authors also generated artificial air cavities in the CTV of one patient (2 and 5 cm diameter), in the high dose gradient region (2 cm), and in the low dose area (2 cm). Treatment plans were optimized without and with each simulated air cavity. For appearing and disappearing air cavities, the CTV V95% and V107% were evaluated. The authors also evaluated the ERE separate from attenuation changes locally around appearing gas pockets.For the ten patients, at 1.5 T, the V95% was influenced by both appearing and disappearing air, and dropped to <98% in 2 out of 50 fractions due a disappearing air cavity of 150 cm(3). V95% differences between 0 and 1.5 T were all within 2%. The V107% was below 1% in 46 out of 50 fractions, and increased to 3% in the remaining fractions due to appearing air of around 120 cm(3). For comparison, V107% was <1% at 0 T for all fractions. In the bowel area, the V15Gy varied strongest from fraction to fraction, but differences between 1.5 and 0 T were minimal with an average difference of 2.3 cm(3) (SD = 18.7 cm(3), p = 0.38). For the simulated air cavities, the ERE resulted in cold-spots maximally 5% lower than prescribed and hot-spots maximally 6% higher than prescribed.The presence of a 1.5 T magnetic field has an impact on the dose distribution when the air content changes of within a few percent in these selected rectal cancer patients. The authors consider this influence of the transverse magnetic field on the dose distribution in IMRT for rectal cancer patients clinically acceptable.

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