Gertjan J L Kaspers

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (336)1804.62 Total impact

  • Molecular Cancer Research 05/2015; DOI:10.1158/1541-7786.MCR-14-0660-T · 4.50 Impact Factor
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    ABSTRACT: Placement of a totally implantable venous access device in children with cancer often leads to hypertrophic scars after its removal. This study investigates whether the use of silicone gel sheets has a beneficial effect on scar outcome in children with cancer. In a three-arm randomized controlled trial, the effects of use of silicone gel sheets for 2 and 6 months were assessed and compared with no intervention in children with cancer after removal of the totally implantable venous access device. Silicone gel sheets were first administered 14 days after surgery. The 1-year follow-up included measurements at seven time points. Next to scar size assessment, the modified Vancouver Scar Scale was used to assess scar outcome. Thirty-six children participated. For hypertrophy, no significant differences were found between the two intervention groups and the control group. However, at 1-year follow-up, the 2-month application group showed significantly smaller scars compared with the group receiving silicone gel sheet treatment for 6 months (p = 0.04), but not when compared with the control group (p = 0.22). Longitudinal multilevel analyses could not confirm these findings and showed no significant intervention effects on both outcomes. This study provides no strong evidence to support the use of silicone gel sheets after totally implantable venous access device removal in children with cancer. There seems to be a small benefit for scar width with application for 2 months. However, for hypertrophy, the scar outcome shows no significant difference between the control group and the 2-month and 6-month treatment groups. Therapeutic, I.
    Plastic and Reconstructive Surgery 04/2015; 135(4):1086-1094. DOI:10.1097/PRS.0000000000001053 · 3.33 Impact Factor
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    ABSTRACT: The purpose of this study is to explore the applicability of a psychosocial intervention in childhood cancer patients. This individualized structured psychosocial program to enhance social-emotional functioning and coping with disease-related effects includes six sessions for children and two sessions for parents. This program was part of a combined intervention with physical exercise. Questionnaires are used to evaluate completion of the psychosocial intervention, coping and satisfaction with the psychosocial intervention by patients and psychologists, and ranking of the individual topics by patients, parents, and psychologists. Of the 30 patients (mean age 13.0 (SD 3.0); 53.3 % male; 30 % still on treatment) who participated in the psychosocial intervention, two dropped out due to medical complications and one due to lack of time; 90 % completed the psychosocial intervention. Overall, patients liked participation in the intervention (4.2 on a 5-point scale; SD 0.8) and were positive about the psychologists (8.1 on a 10-point scale; SD 1.3). Psychologists rated the intervention on several points (e.g., clarity of the manual and content of the intervention), and mean scores ranged from 7.1 (SD 1.1) to 8.6 (SD 0.9) on 10-point scales. Minor adaptations were suggested by patients and psychologists, including customizing according to age and a more patient-tailored approach. This psychosocial intervention for childhood cancer patients appears to be applicable. Future studies need to establish whether this intervention combined with a physical exercise intervention actually improves psychosocial functioning of childhood cancer patients. When proven effective, this combined intervention can be offered to childhood cancer patients and may enhance their physical health and quality of life.
    Supportive Care Cancer 01/2015; DOI:10.1007/s00520-014-2576-6 · 2.50 Impact Factor
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    ABSTRACT: Over the past decade, the proteasome inhibitor bortezomib (Velcade) has not only gained a cornerstone position in the treatment of hematological malignancies, particularly multiple myeloma and mantle cell lymphoma, but also in experimental therapeutics of acute leukemia. However, the therapeutic efficacy of bortezomib is hampered by the emergence of acquired resistance, for which multifactorial mechanisms have been identified. This review summarizes the current status of the molecular mechanisms underlying resistance to proteasome inhibitors that emerged in preclinical therapeutic studies, and discusses these findings in the clinical perspective of novel therapeutic modalities of hematological malignancies. The specific topics that will be addressed in the current review include the recently established mechanisms of resistance to proteasome inhibitors: the role of constitutive and immunoproteasomes, mutations in proteasome subunits, unfolded protein response, XBP1 and MARCKS proteins, multidrug efflux transporters, aggresomes and autophagy, as well as the impact of pro-survival signaling pathways and bone marrow microenvironment. The growing knowledge of the determinants that confer bortezomib resistance and/or toxicity has provided the basis for the rational development of second generation proteasome inhibitors, some of which were recently approved or that are undergoing clinical evaluation as novel strategies to overcome bortezomib resistance as well as to enhance clinical therapeutic efficacy along with minimal side effects. Collectively, these combined approaches should enhance therapeutic efficacy and outcome in patients with hematological malignancies.
    Drug Resistance Updates 12/2014; 18. DOI:10.1016/j.drup.2014.12.001 · 8.82 Impact Factor
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    ABSTRACT: Background Wilms tumour postoperative chemotherapy is ideally stratified according to the pathologist's assessment of tumour stage and risk classification (tumour type). In sub-Saharan Africa results are often not available in time to influence therapy and in Malawi surgical staging has been used to stratify postoperative chemotherapy. Here we compare the results from surgical and both local pathology and central pathology review.ProcedureChildren diagnosed with a Wilms tumour in Blantyre, Malawi between 2007 and 2011 were included if they had a nephrectomy and the pathology slides were available. All tumour specimens were assessed in three different ways: the local surgeon documented the surgical stage of the tumour, and the risk classification and pathology stage were assessed both by the local pathologist and by a SIOP central review pathologist in Europe.ResultsFifty patients had complete data available and were included in the analyses. Tumour risk classification differed between the local and central pathology review in only two patients (4%). Using central pathology review as the gold standard 60% of patients received the correct postoperative chemotherapy treatment based on surgical staging and 84% based on the local pathology stage and risk classification.Conclusion Local pathology capacity building is needed to enable timely assessment and reporting. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 12/2014; 61:2180-2184. DOI:10.1002/pbc.25138 · 2.56 Impact Factor
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    ABSTRACT: Children with and after cancer are found to have a decreased physical fitness, frequently resulting in decreased physical functioning. The gold standard test for assessing aerobic fitness, a component of physical fitness, is the respiratory gas analyses--based cardiopulmonary exercise test (CPET). However, equipment for gas analysis is often unavailable in local physical therapy centres and non--university hospitals. The Steep Ramp Test (SRT), is a cycle ergometer test with a fast increase in workload, a short duration, and does not require respiratory gas analysis equipment. The aim of this study was to compare the results of the CPET and the SRT, in children with cancer, and to assess whether the SRT can be used for aerobic fitness assessment in clinical practice in this population. This study is a cross--sectional assessment using baseline data of a randomized controlled trial. The study was performed in a hospital setting. Sixty--one children (mean age 12.9 years; 33 boys) with cancer were included in the analysis; 16 children were on non--intensive chemotherapy treatment, 45 were in the first year thereafter. Participants performed both the SRT and the CPET on a cycle ergometer with respiratory gas analysis. Data of the two tests were compared and regression analyses were performed. CPET test results revealed a higher impact on the cardiovascular system, as shown by higher peak ventilation (47.8 versus 52.0 Litres per min) and peak heart rates (173 versus 191 beats per min), compared to the SRT. In addition, the test time was significantly longer (90 s versus 390 s). Yet, the primary outcome of the SRT (peak work rate) was able to reliably estimate the peak oxygen uptake of the CPET. The peak oxygen uptake was comparable between the SRT and the CPET, although the peak work rate was significantly higher during the SRT. This study showed that the SRT is a valid instrument to assess aerobic fitness in children with cancer. The SRT is less time consuming and can be performed without gas analysis in a non--clinical setting, making it less demanding for children.
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    ABSTRACT: Background: According to the results of the international study Relapsed AML 2001/01 response was better after re-induction with L-DNR/FLAG (liposomal daunorubicin, fludarabine, cytarabine, G-CSF) compared to FLAG only but survival rate was not improved. However, the findings might be group-specific. Method: Patient characteristics, actual therapy given and long-term course of the disease in 155 pediatric patients (including non-randomized) with first relapse and 10 primary nonresponders treated in Germany were analyzed. Results: Overall 4-year survival rates after relapse were similar in the 2 treatment groups L-DNR/FLAG and FLAG (0.43±0.05 vs. 0.47±0.06, p(log-rank)=0.47). The rate of randomization was low (65%) and 5% of the 101 randomized patients changed the treatment arm. Therefore, induction was based in 40% patients on an individual decision with preference for L-DNR/FLAG. There were less patients with favorable cytogenetics and morphology in the L-DNR/FLAG-group (p<0.04). Response to the first re-induction course at day 28 tended to be more unfavorable with FLAG only. In this patient group protocol intensifications were more frequent as compared to the L-DNR/FLAG-group (p=0.07), and late CR could be achieved after intensification in 9/18 poor responding patients. Conclusion: The initial selection bias of relapse patients with unfavorable risk factors to the disadvantage of the L-DNR/FLAG-group and the more drug- and time-intensive treatment after 1(st) re-induction given in the FLAG-group may have nullified the initial beneficial effect of L-DNR containing re-induction therapy and led to similar and relatively favorable survival rates in both treatment groups in Germany. © Georg Thieme Verlag KG Stuttgart · New York.
    Klinische Pädiatrie 11/2014; 226(6/07):323-331. DOI:10.1055/s-0034-1385918 · 1.90 Impact Factor
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    ABSTRACT: Our study explores socioeconomic, treatment-related, and psychological experiences of parents during cancer treatment of their children at an academic hospital in Kenya.
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    ABSTRACT: Systemic delivery of therapeutic agents remains ineffective against diffuse intrinsic pontine glioma (DIPG), possibly due to an intact blood-brain-barrier (BBB) and to dose-limiting toxicity of systemic chemotherapeutic agents. Convection-enhanced delivery (CED) into the brainstem may provide an effective local delivery alternative for DIPG patients.
    Journal of Neuroscience Methods 09/2014; 238. DOI:10.1016/j.jneumeth.2014.09.020 · 1.96 Impact Factor
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    ABSTRACT: Adrenocortical carcinoma (ACC) is rare in both adult and pediatric populations. Literature suggests significant differences between children and adults in presentation, histological properties and outcome. The aim of this first nationwide study on pediatric ACC was to describe the incidence, presentation, pathological characteristics, treatment and survival in The Netherlands. All ACC patients aged <20 years at diagnosis and registered in the population-based Netherlands Cancer Registry between 1993 and 2010 were included. Clinical data were extracted from medical records. Archival histological slides were collected via the Dutch Pathology Registry (PALGA). We compared our findings to all clinical studies on pediatric ACC that were found on PubMed. Based on the results, 12 patients were identified: 8 females and 4 males. The median age was 4.1 years (range 1.1-18.6). The population-based age-standardized incidence rate for patients <20 years was 0.18 per million person-years. Autonomous hormonal secretion was present in 10 patients. Seven patients were aged ≤4 years at diagnosis, 5 presented with localized disease and 2 with locally advanced disease. Five patients were aged ≥5 years, 3 presented with distant metastases and 1 with locally advanced disease. For all patients, histological examination displayed malignant characteristics. All patients aged ≤4 years at diagnosis survived; the median follow-up was 97 months (57-179 months). All patients aged ≥5 years died; the median survival was 6 months (0-38 months). Pediatric ACC is extremely rare in the Western world. The clinical outcome was remarkably better in patients aged ≤4 years. This is in accordance with less advanced stage of disease at presentation, yet contrasts with the presence of adverse histological characteristics. Clinical management in advanced disease is adapted from adult practice in the absence of evidence regarding pediatric ACC.
    Oncology Reports 09/2014; DOI:10.3892/or.2014.3506 · 2.19 Impact Factor
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    ABSTRACT: Several studies in adults have shown patient reported outcomes (PROs) to be effective in enhancing patient-physician communication and discussion of Health Related Quality of Life outcomes. Although less studied, positive results have been demonstrated in children. A PRO-intervention needs to be feasible in clinical practice to be successful. In the current study, 74 parents of children who successfully completed their cancer treatment and 21 pediatric oncologists (POs) evaluated a PRO-intervention and gave recommendations for future use in their practice. Most parents and POs suggested PROs to be an important part of standard care, starting during treatment, with an assessment frequency of every 3 months. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 09/2014; 61(9). DOI:10.1002/pbc.25034 · 2.56 Impact Factor
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    ABSTRACT: Improvement in survival of pediatric acute lymphoblastic leukemia (ALL) has increased the attention to quality of life (QoL) . QoL is impaired during maintenance treatment, but little is known about QoL during induction therapy. Identification of patients with poor QoL during induction will provide opportunities for early interventions, and may subsequently improve future QoL. This national multi-center study aimed to assess QoL and its determinants during ALL induction treatment. Proxy reports of the Child Health Questionnaire (CHQ) and the PedsQL cancer version were collected. Child, treatment, and parental characteristics were analyzed as potential determinants in a multiple regression model. One hundred thirty parents of children participated (response rate 82 %), median child age was 5.7 years and 48 % were female. QoL, as measured with the CHQ, was significantly lower than the norm, the effect sizes were large, and the differences were clinically relevant. Physical QoL was more often affected than psychosocial QoL. Regression models could be constructed for 4/ 10 CHQ scales and 6/ 8 PedsQL cancer scales, accounting for 7 to 36 % of the variance in scores. Impaired QoL was most often associated with older children, girls, and time since diagnosis. Also, father respondents seem to have a lower QoL perception compared to mother respondents although this needs to be confirmed in future research. Specific counseling for subsets of patients with a higher risk of low QoL during the early phases of therapy is warranted.
    Supportive Care Cancer 07/2014; 22(12). DOI:10.1007/s00520-014-2349-2 · 2.50 Impact Factor
  • Pediatric Hematology and Oncology 07/2014; DOI:10.3109/08880018.2014.924611 · 0.96 Impact Factor
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    ABSTRACT: Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n = 198) of relapsed non-French-American-British M3, non-Down syndrome AML patients that received similar relapse treatment. We correlated molecular aberrations with clinical and biological factors and studied their prognostic relevance. Hotspot mutations in the analysed genes were detected in 92 out of 198 patients (46·5%). In 72 of these 92 patients (78%), molecular aberrations were mutually exclusive for the currently analysed genes. FLT3-internal tandem repeat (ITD) (18% of total group) mutations were most frequent, followed by NRAS (10·2%), KRAS (8%), WT1 (8%), KIT (8%), NPM1 (5%) and FLT3-tyrosine kinase domain (3%) mutations. Presence of a WT1 aberration was an independent risk factor for second relapse (Hazard Ratio [HR] = 2·74, P = 0·013). In patients who achieved second complete remission (70·2%), WT1 and FLT3-ITD aberrations were independent risk factors for poor overall survival (HR = 2·32, P = 0·038 and HR = 1·89, P = 0·045 respectively). These data show that molecular aberrations at first relapse are of prognostic relevance and potentially useful for risk group stratification of paediatric relapsed AML and for identification of patients eligible for personalized treatment.
    British Journal of Haematology 06/2014; 166(6). DOI:10.1111/bjh.12989 · 4.96 Impact Factor
  • Acta Neuropathologica 06/2014; 128(4). DOI:10.1007/s00401-014-1307-x · 9.78 Impact Factor
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    ABSTRACT: Drug resistance is a major issue in the treatment of glioblastoma. Almost all glioblastomas are intrinsically resistant to chemotherapeutic temozolomide (TMZ) or develop resistance during treatment. The interaction networks of microRNAs (miRNAs) and mRNAs likely regulate most biological processes and can be employed to better understand complex processes including drug resistance in cancer. In this study, we examined if integrative miRNA/mRNA network analysis using the web-service tool mirConnX could be used to identify drug resistance factors in glioblastoma. We used TMZ-resistant glioblastoma cells and their integrated miRNA/mRNA networks to identify TMZ-sensitizing factors. TMZ resistance was previously induced in glioblastoma cell lines U87, Hs683, and LNZ308. miRNA/mRNA expression profiling of these cells and integration of the profiles using mirConnX resulted in the identification of plant homeodomain (PHD)-like finger 6 (PHF6) as a potential TMZ-sensitizing factor in resistant glioblastoma cells. Analysis of PHF6 expression showed significant upregulation in glioblastoma as compared to normal tissue. Interference with PHF6 expression in three TMZ-resistant subclones significantly enhanced TMZ-induced cell kill in two of these cell lines. Altogether, these results demonstrate that mirConnX is a feasible and useful tool to investigate miRNA/mRNA interactions in TMZ-resistant cells and has potential to identify drug resistance factors in glioblastoma.
    Scientific Reports 06/2014; 4:5260. DOI:10.1038/srep05260 · 5.08 Impact Factor
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    ABSTRACT: Although diffuse intrinsic pontine glioma (DIPG) carries the worst prognosis of all pediatric brain tumors, studies on prognostic factors in DIPG are sparse. To control for confounding variables in DIPG studies, which generally include relatively small patient numbers, a survival prediction tool is needed.
    Neuro-Oncology 06/2014; DOI:10.1093/neuonc/nou104 · 5.29 Impact Factor
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    ABSTRACT: Background The principal reason for childhood cancer treatment failure in low-income countries is treatment abandonment, the most severe form of nonadherence. Two often neglected factors that may contribute to treatment abandonment are as follows: (a) lack of information and guidance by doctors, along with the negative beliefs of family and friends advising parents, which contributes to misconceptions regarding cancer and its treatment, and (b) a widespread policy in public hospitals by which children are retained after doctor's discharge until medical bills are settled.Objective This study explored parents' experiences with hospital retention policies in a Kenyan academic hospital and the impact of attitudes of family and friends on parents' decisions about continuing cancer treatment for their child.Methods Home visits were conducted to interview parents of childhood cancer patients who had been diagnosed between 2007 and 2009 and who had abandoned cancer treatment.ResultsRetrospective chart review revealed 98 children diagnosed between 2007 and 2009 whose parents had made the decisions to abandon treatment. During 2011–2012, 53 families (54%) could be reached, and 46 (87%) of these agreed to be interviewed. Parents reported the attitudes of community members (grandparents, relatives, friends, villagers, and church members); 61% believed that the child had been bewitched by some individual, and 74% advised parents to seek alternative treatment or advised them to stop medical treatment (54%). Parents also reported that they were influenced by discussions with other parents who had a child being treated, including that their child's life was in God's hands (87%), the trauma to the child and family of forced hospital stays (84%), the importance of completing treatment (81%), the financial burden of treatment (77%), and the incurability of cancer (74%). These discussions influenced their perceptions of cancer treatment and its usefulness (65%). Thirty-six families (78%) had no health insurance, and 19 of these parents (53%) could not pay their medical bills and were not allowed to take their child home when treatment ended. Parents reported feelings of desperation (95%), powerlessness (95%), and sadness (84%) and that their child has been imprisoned (80%), during the period of retention. The majority of parents (87%) felt that hospital retention of children must cease.Conclusions The attitudes and beliefs of parents of children with cancer are impacted by those close to them and their community and may influence their perceptions of cancer treatment and decisions to stop treatment. Hospital retention policies are highly distressing for parents and may contribute to both treatment delays and treatment abandonment. These factors jeopardize treatment outcomes for young patients and require attention and modification. Copyright © 2014 John Wiley & Sons, Ltd.
    Psycho-Oncology 06/2014; 23(6). DOI:10.1002/pon.3571 · 4.04 Impact Factor
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    ABSTRACT: Background: Chemotherapy and radiotherapy for childhood cancer can result in a decreased reproductive function. It is therefore important that paediatric oncologists discuss the possible impact of treatment on female fertility and available fertility preservation options with their patients. However, it is unknown what Dutch paediatric oncologists know about of the effect of cancer treatment on female fertility, whether or not they address this issue in clinical practice, what their attitudes are towards addressing fertility after cancer treatment and fertility preservation options, and to what extent they require additional information resources. Methods: In this nationwide quantitative cross-sectional study a survey was sent to all registered paediatric oncologists in the Netherlands (n=64). Results: Thirty-seven paediatric oncologists participated (participation rate 58%). Fertility issues were discussed with patients and÷or parents by 97%. Of the paediatric oncologists, 54-76% were aware of possibilities for fertility preservation; however only.
    The Netherlands Journal of Medicine 06/2014; 72(5):264-70. · 2.21 Impact Factor
  • Gertjan Kaspers
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    ABSTRACT: The prognosis of paediatric acute myeloid leukaemia (AML) has improved significantly over the recent decades, but still about one-third of patients relapse. These patients have a relatively poor prognosis, with a probability of long-term survival from relapse of about 35%. This can only be achieved with very intensive chemotherapy and, usually, allogeneic stem cell transplantation, leading to very significant toxicity and even treatment-related mortality. Major improvements in the treatment of paediatric relapsed AML thus are required still, and several possibilities are discussed. In case of a suspected relapse, a comprehensive diagnostic work-up has to be undertaken, because significant changes in the biological features of the AML cells may have occurred between initial diagnosis and relapse. This review discusses many practical issues that one encounters in the treatment of children with relapsed AML. It will also be of interest for those involved in translational research in AML.
    British Journal of Haematology 05/2014; 166(5). DOI:10.1111/bjh.12947 · 4.96 Impact Factor

Publication Stats

6k Citations
1,804.62 Total Impact Points

Institutions

  • 2002–2014
    • VU University Medical Center
      • • Department of Clinical Genetics
      • • Department of Pediatrics
      • • Department of Haematology
      Amsterdamo, North Holland, Netherlands
  • 1994–2014
    • VU University Amsterdam
      • • Department of Pediatric Hematology/Oncology
      • • Department of Medical Oncology
      Amsterdamo, North Holland, Netherlands
    • Post University
      Post, Texas, United States
  • 2013
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
    • University of New South Wales
      Kensington, New South Wales, Australia
    • National Heart, Lung, and Blood Institute
      • Hematology Branch
      Maryland, United States
  • 2006–2013
    • Dutch Childhood Oncology Group
      Rotterdam, South Holland, Netherlands
  • 2011
    • Leiden University Medical Centre
      • Department of Pediatrics
      Leiden, South Holland, Netherlands
  • 2010–2011
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 2009
    • University of Groningen
      Groningen, Groningen, Netherlands
    • St. Jude Medical
      Little Canada, Minnesota, United States
    • Aarhus University Hospital
      • Department of Pediatrics
      Aarhus, Central Jutland, Denmark
  • 2008–2009
    • Charles University in Prague
      • Department of Paediatric Haematology and Oncology (2. LF)
      Praha, Praha, Czech Republic
    • Università degli Studi di Milano-Bicocca
      Milano, Lombardy, Italy
  • 2004
    • University of Münster
      Muenster, North Rhine-Westphalia, Germany
  • 2003
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
    • Kent Hospital
      Warwick, Rhode Island, United States
  • 1999–2002
    • University of Hamburg
      Hamburg, Hamburg, Germany
  • 2001
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 1991–2000
    • University of Amsterdam
      • Department of Paediatrics
      Amsterdamo, North Holland, Netherlands
  • 1995
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands