Sjoukje Oosting - Academia.edu (original) (raw)
Papers by Sjoukje Oosting
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 12, 2016
Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth ... more Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor (VEGF)-A produced locally is supposed to play an important role in development of disease manifestations and is a target for antiangiogenic therapy with the monoclonal antibody bevacizumab. We aimed to assess whether VHL manifestations can be visualized with 89Zirconium-bevacizumab positron emission tomography ((89)Zr-bevacizumab PET) and to explore whether (89)Zr-bevacizumab PET can differentiate progressive from non-progressive lesions. VHL patients with at least one measurable hemangioblastoma were eligible. An intravenous injection with 37MBq (89)Zr-bevacizumab was administered 4 days before the scan. Maximum standardized uptake values were calculated. PET-scans were fused with routine magnetic resonance imaging (MRI) of the central nervous ...
Asco Meeting Abstracts, May 20, 2012
Ejc Suppl, 2010
A major challenge in cancer drug development is early selection of most promising drug candidate(... more A major challenge in cancer drug development is early selection of most promising drug candidate(s) for a specific target and to identify the patient (sub)populations most likely to benefit from such a drug. Therefore there is a need for techniques that can rapidly and precisely elucidate the pharmacokinetic and pharmacodynamic profile of new drugs in patients, and for (predictive) biomarkers of antitumor drug efficacy. Molecular imaging can potentially fulfill all these tasks and can be performed with several modalities, including magnetic resonance imaging, optical imaging, and radionuclide imaging with positron emission tomography (PET) or single photon emission computed tomography (SPECT). Most clinical molecular imaging data are gathered on the visualization of general processes, such as glucose metabolism and DNA synthesis with [ 18 F]fluorodeoxyglucose (FDG) and [ 18 F]fluoro-L-thymidine (FLT) PETimaging, respectively. Molecular imaging can also visualize tumor cell characteristics that are relevant for treatment, like hormone receptors, growth factors and growth factor receptors. It potentially provides serial non-invasive information about the status of these characteristics within the tumor and across lesions in the entire body. PET imaging of the estrogen receptor (ER) with 18 F-fluoro-17-b-estradiol (FES) proved feasible in breast cancer patients, whereas the androgen receptor (AR) was successfully imaged with 18 F-fluoro-5a-dihydrotestosterone (FDHT) in prostate cancer patients. FDHT-PET showed that MDV3100, an AR antagonist that blocks androgens from binding to the AR, substantially reduced FDHT binding (Scher et al, Lancet 2010). We imaged HER2 in metastatic breast cancer patients with 111 Intrastuzumab SPECT and 89 Zr-trastuzumab PET. 89 Zr-trastuzumab showed quantifiable tumor uptake and provided new insights in trastuzumab pharmacokinetics. 111 In-bevacizumab SPECT and 89 Zr-bevacizumab PET visualized VEGF in lesions of several tumor types. SPECT imaging of the TRAIL-R1 with 111 In-mapatumumab showed variable tumor uptake between patients. HER2 and VEGF-PET proved an excellent read out of downregulation of HER2 and VEGF by HSP90 inhibitors and of VEGF by mTOR inhibitors in xenograft mouse models. Preclinical VEGF imaging provided insights in the heterogeneous vascular tumor responses to sunitinib. These observations are now tested in clinical trials. Preclinical HER2-PET imaging showed decreased tumor tracer uptake after lapatinib treatment, due to inhibition of tracer internalization. Thus, new molecular imaging can identify the levels of a specific tumor target across the entire body over time, can provide new mechanistic and pharmacological insight and can contribute to development and selection of drug candidates and distinguish patients most likely to benefit from the treatment.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinom... more No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinoma (mRCC) exist. Tumor vascular endothelial growth factor A (VEGF-A) level may be useful. We determined tumor uptake of (89)Zr-bevacizumab, a VEGF-A-binding PET tracer, in mRCC patients before and during antiangiogenic treatment in a pilot study. Patients underwent (89)Zr-bevacizumab PET scans at baseline and 2 and 6 wk after initiating either bevacizumab (10 mg/kg every 2 wk) with interferon-α (3-9 million IU 3 times/wk) (n = 11) or sunitinib (50 mg daily, 4 of every 6 wk) (n = 11). Standardized uptake values were compared with plasma VEGF-A and time to disease progression. (89)Zr-bevacizumab PET scans visualized 125 evaluable tumor lesions in 22 patients, with a median SUV(max) (maximum standardized uptake value) of 6.9 (range, 2.3-46.9). Bevacizumab/interferon-α induced a mean change in tumor SUV(max) of -47.0% (range, -84.7 to +20.0%; P < 0.0001) at 2 wk and an additional -9.7% (ra...
Nederlands tijdschrift voor geneeskunde, 2011
Testicular carcinoma is a rare tumour but the most frequently occurring form of cancer in men age... more Testicular carcinoma is a rare tumour but the most frequently occurring form of cancer in men aged 18-35 years. In metastatic disease, following orchidectomy three or four courses of combination chemotherapy with cisplatin are given. With a general chance of cure of 80-90%, testicular cancer is still regarded as a model for a form of cancer that is curable. Due to this favourable prognosis--and to its rising incidence--the group of people who survive testicular cancer is growing and more attention is being paid to the risk of adverse consequences of treatment: secondary tumours and cardiovascular morbidity. Shared care follow-up for testicular cancer survivors with participation of both primary and secondary care is currently developed.
The Lancet Oncology, 2010
The metabolic syndrome, as a cluster of cardiovascular risk factors, may represent an important c... more The metabolic syndrome, as a cluster of cardiovascular risk factors, may represent an important connection between cancer treatment and its common late eff ect of cardiovascular disease. Insight into the aetiology of the metabolic syndrome after cancer treatment might help to identify and treat cancer survivors with increased cardiovascular risk. In this review, we summarise current knowledge on the prevalence and pathophysiology of the metabolic syndrome in cancer survivors, and discuss current intervention strategies with an emphasis on new developments.
Journal of Nuclear Medicine, 2014
Everolimus increases progression-free survival in patients with advanced neuroendocrine tumors (N... more Everolimus increases progression-free survival in patients with advanced neuroendocrine tumors (NETs). Currently, no biomarkers are available for early selection of patients who will benefit from everolimus. Everolimus can reduce vascular endothelial growth factor A (VEGF-A) production by tumor cells. Therefore, we aimed to investigate the effect of everolimus on tumor uptake of the radioactive-labeled VEGF-A antibody bevacizumab with PET in NET patients. Methods: Patients with advanced progressive well-differentiated NETs underwent 89 Zr-bevacizumab PET scans before and at 2 and 12 wk during everolimus treatment. 89 Zr-bevacizumab uptake was quantified by the maximum standardized uptake value (SUV max ). Tumor response and the percentage change in the sum of target lesion diameters were determined according to Response Evaluation Criteria in Solid Tumors 1.1 on CT (3 monthly). Results: In 4 of the 14 patients entered, no tumor lesions were visualized with 89 Zr-bevacizumab PET. In the remaining patients, 19% of tumor lesions 1 cm or greater known by CT were visualized. Tumor SUV max decreased during everolimus treatment, with a median of −7% at 2 wk (P 5 0.09) and a median of −35% at 12 wk (P , 0.001). The difference in SUV max at 2 and 12 wk with respect to SUV max at baseline correlated with percentage change on CT at 6 mo (r 2 5 0.51, P , 0.05, and r 2 5 0.61, P , 0.01, respectively). Conclusion: This study demonstrates variable 89 Zr-bevacizumab PET tumor uptake in NET patients. 89 Zr-bevacizumab tumor uptake diminished during everolimus treatment. Serial 89 Zr-bevacizumab PET might be useful as an early predictive biomarker of anti-VEGFdirected treatment in NET patients.
Cancer Research, 2011
Non-invasive imaging of angiogenesis could ease the optimization of antiangiogenesis treatments f... more Non-invasive imaging of angiogenesis could ease the optimization of antiangiogenesis treatments for cancer. In this study, we evaluated the role of VEGF-PET as a biomarker of dynamic angiogenic changes in tumors following treatment with the kinase inhibitor sunitinib. The effects of sunitinib treatment and withdrawal on the tumor was investigated using the new VEGF-PET tracer (89)Zr-ranibizumab as well as (18)F-FDG PET, and (15)O-water PET in mouse xenograft models of human cancer. The obtained imaging results were compared with tumor growth, VEGF plasma levels and immunohistologic analyzes. In contrast to (18)F-FDG and (15)O-water PET, VEGF-PET demonstrated dynamic changes during sunitinib treatment within the tumor with a strong decline in signal in the tumor center and only minimal reduction in tumor rim, with a pronounced rebound after sunitinib discontinuation. VEGF-PET results corresponded with tumor growth and immunohistochemical vascular- and tumor- markers. Our findings highlight the strengths of VEGF-PET imaging to allow serial analysis of angiogenic changes in different areas within a tumor.
Health expectations : an international journal of public participation in health care and health policy, Jan 15, 2017
Audit and feedback on professional practice and health care outcomes are the most often used inte... more Audit and feedback on professional practice and health care outcomes are the most often used interventions to change behaviour of professionals and improve quality of health care. However, limited information is available regarding preferred feedback for patients, professionals and health insurers. Investigate the (differences in) preferences of receiving feedback between stakeholders, using the Dutch Head and Neck Audit as an example. A total of 37 patients, medical specialists, allied health professionals and health insurers were interviewed using semi-structured interviews. Questions focussed on: "Why," "On what aspects" and "How" do you prefer to receive feedback on professional practice and health care outcomes? All stakeholders mentioned that feedback can improve health care by creating awareness, enabling self-reflection and reflection on peers or colleagues, and by benchmarking to others. Patients prefer feedback on the actual professional pract...
International journal of radiation oncology, biology, physics, Jan 6, 2017
We sought to assess the effect of age on overall survival (OS), cancer-specific survival (CSS), a... more We sought to assess the effect of age on overall survival (OS), cancer-specific survival (CSS), and non-cancer-related death (NCRD) in elderly (aged ≥70 years) head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radiation therapy. The results were compared with those of younger patients, and the most important prognostic factors for survival endpoints were determined. Treatments may be better justified based on identification of the main differences in survival between young and elderly patients. Data were analyzed from all consecutive HNSCC patients treated with definitive radiation therapy (66-70 Gy) in our department between April 2007 and December 2014. A total of 674 patients, including 168 elderly patients (24.9%), were included in the study. Multivariate association models were constructed to assess the effect of age on survival endpoints. Multivariate analysis was performed to identify potential prognostic factors for survival in elderly patients. ...
Journal of Nuclear Medicine, 2017
Currently, biomarkers that predict efficacy of everolimus in metastatic renal cell carcinoma (mRC... more Currently, biomarkers that predict efficacy of everolimus in metastatic renal cell carcinoma (mRCC) patients are lacking. Everolimus inhibits vascular endothelial growth factor A (VEGF-A) expression. We performed PET scans in mRCC patients with (89)Zr-bevacizumab, a VEGF-A-binding antibody tracer. Aims were to determine change in tumor tracer uptake after start of everolimus and to explore if (89)Zr-bevacizumab PET can identify patients with early disease progression. (89)Zr-bevacizumab PET was done before and 2 and 6 weeks after start of everolimus 10 mg/day in mRCC patients. Routine CT scans were performed at baseline and every 3 months thereafter. Tumor tracer uptake was quantified using maximum Standardized Uptake Value (SUVmax). Endpoints were change in tumor tracer uptake and treatment response on CT after 3 months. Thirteen patients participated. Median SUVmax of 94 tumor lesions was 7.3 (range 1.6-59.5). Between patients, median tumor SUVmax varied up to 8-fold. After 2 weeks, median SUVmax was 6.3 (1.7-62.3) corresponding to a mean decrease of 9.1% (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Three patients discontinued everolimus early. At 6 weeks, a mean decrease in SUVmax of 23.4% compared to baseline was found in 70 evaluable lesions of 10 patients, with a median SUVmax of 5.4 (1.1-49.4, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). All 10 patients who continued treatment had stable disease at 3 months. Everolimus decreases (89)Zr-bevacizumab tumor uptake. Further studies are warranted to evaluate predictive value of (89)Zr-bevacizumab PET for everolimus antitumor efficacy.
Critical Issues in Head and Neck Oncology, 2016
Head & neck, Jan 10, 2016
There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermedia... more There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck. All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed. We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%. In 50 patients with surgically resected high- or intermediate-grade osteosarcoma of the head and neck younger than 75 years, univariate and multivariable analysis, adjusting for age and resection margins, showed that patients who had not received chemotherapy had a significantly higher risk of local recurrence (hazard ratio [HR] = 3.78 and 3.66, respectively). In patients younger than 75 years of age with surgically resected high- and intermediate-grade osteosarcoma of the head and neck, treatment with (neo-)adjuvant chemotherapy resulted in a significantly smaller risk of local...
Oral oncology, 2016
To compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus w... more To compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus weekly cisplatin during adjuvant radiotherapy for high-risk head and neck squamous cell carcinoma (HNSCC). Consecutive HNSCC patients with involved resection margins and/or extra-capsular extension in two tertiary cancer centers with different institutional practices were identified. Cumulative cisplatin dose was calculated and information on toxicity reviewed and compared between patients who received 3-weekly versus weekly cisplatin. Of 270 high risk patients, 60 received 3-weekly 100mg/m(2) and 48 received weekly 50mg/m(2) cisplatin during adjuvant radiotherapy (60-66Gy in 30-33 fractions). Fourteen patients received other chemotherapy schedules and 148 received no chemotherapy. Mean cumulative cisplatin dose was 199.4mg/m(2) (standard error (SE) 5.4) in 3-weekly versus 239.8mg/m(2) (SE 11.0, P=0.001) in weekly treated patients. Cumulative cisplatin ⩾200mg/m(2) was given to 67.7% of pa...
The oncologist, Jan 21, 2016
In metastatic testicular cancer patients treated with bleomycin, etoposide, and cisplatin (BEP) c... more In metastatic testicular cancer patients treated with bleomycin, etoposide, and cisplatin (BEP) chemotherapy, bleomycin-induced pneumonitis is a well-known and potentially fatal side effect. We sought to determine the prevalence of lesions as signs of bleomycin-induced pulmonary changes on restaging computed tomography (CT) scans after treatment and to ascertain whether fibrosis markers were predictive of these changes. This prospective nonrandomized cohort study included metastatic testicular cancer patients, 18-50 years of age, treated with BEP chemotherapy. Restaging CT scans were examined for lesions as signs of bleomycin-induced pulmonary changes by two independent radiologists and graded as minor, moderate, or severe. Plasma samples were collected before, during, and after treatment and were quantified for transforming growth factor-β1 (TGF-β1), growth differentiation factor-15 (GDF-15), and high-sensitivity C-reactive protein (hs-CRP). In total, 66 patients were included: For...
Plos One, 2014
Background: Curative radiotherapy or chemoradiation for head and neck cancer (HNC) may result in ... more Background: Curative radiotherapy or chemoradiation for head and neck cancer (HNC) may result in severe acute and late side effects, including tube feeding dependence. The purpose of this prospective cohort study was to develop a prediction model for tube feeding dependence 6 months (TUBE M6 ) after curative (chemo-) radiotherapy in HNC patients. Patients and Methods: Tube feeding dependence was scored prospectively. To develop the multivariable model, a group LASSO analysis was carried out, with TUBE M6 as the primary endpoint (n = 427). The model was then validated in a test cohort (n = 183). The training cohort was divided into three groups based on the risk of TUBE M6 to test whether the model could be extrapolated to later time points (12, 18 and 24 months).
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 12, 2016
Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth ... more Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor (VEGF)-A produced locally is supposed to play an important role in development of disease manifestations and is a target for antiangiogenic therapy with the monoclonal antibody bevacizumab. We aimed to assess whether VHL manifestations can be visualized with 89Zirconium-bevacizumab positron emission tomography ((89)Zr-bevacizumab PET) and to explore whether (89)Zr-bevacizumab PET can differentiate progressive from non-progressive lesions. VHL patients with at least one measurable hemangioblastoma were eligible. An intravenous injection with 37MBq (89)Zr-bevacizumab was administered 4 days before the scan. Maximum standardized uptake values were calculated. PET-scans were fused with routine magnetic resonance imaging (MRI) of the central nervous ...
Asco Meeting Abstracts, May 20, 2012
Familial cancer, Jan 26, 2016
Central nervous system hemangioblastomas occur sporadically and in patients with von Hippel-Linda... more Central nervous system hemangioblastomas occur sporadically and in patients with von Hippel-Lindau (VHL) disease due to a VHL germline mutation. This mutation leads to enhanced transcription of chemokine receptor 4 (CXCR4), its ligand (CXCL12) and vascular endothelial growth factor A (VEGFA). We aimed to determine in VHL-related and sporadic hemangioblastomas CXCR4, CXCL12, and VEGFA protein expression and to correlate this to hemangioblastoma size and expression in normal surrounding tissue. 27 patients with a hemangioblastoma were included for analysis of immunohistochemistry of tissue, MRI and DNA. Hemangioblastomas overexpress CXCR4, CXCL12, and VEGFA compared to normal surrounding tissue. In sporadic hemangioblastomas the mean percentage of CXCR4 positive hemangioblastoma cells was 16 %, SD 8.4, in VHL-related hemangioblastomas 8 %, SD 4.4 (P = 0.002). There was no relation between preoperative tumor size and CXCR4 or CXCL12 expression. Compared to normal surrounding tissue CXC...
Oncotarget, Jan 14, 2016
Vascular endothelial growth factor (VEGF) pathway targeting agents have been combined with other ... more Vascular endothelial growth factor (VEGF) pathway targeting agents have been combined with other anticancer drugs, leading to improved efficacy in carcinoma of the cervix, stomach, lung, colon and rectum, ovary, and breast. Vessel normalization induced by VEGF pathway targeting agents influences tumor drug uptake. Following bevacizumab treatment, preclinical and clinical studies have shown a decrease in tumor delivery of radiolabeled antibodies and two chemotherapeutic drugs. The decrease in vessel pore size during vessel normalization might explain the decrease in tumor drug uptake. Moreover, the addition of bevacizumab to cetuximab, or panitumumab in colorectal cancer patients or to trastuzumab in breast cancer patients, did not improve efficacy. However, combining bevacizumab with chemotherapy did increase efficacy in some cancer types. Novel biomarkers to select patients who may benefit from combination therapies, such as the effect of an angiogenesis inhibitor on tumor perfusio...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 12, 2016
Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth ... more Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor (VEGF)-A produced locally is supposed to play an important role in development of disease manifestations and is a target for antiangiogenic therapy with the monoclonal antibody bevacizumab. We aimed to assess whether VHL manifestations can be visualized with 89Zirconium-bevacizumab positron emission tomography ((89)Zr-bevacizumab PET) and to explore whether (89)Zr-bevacizumab PET can differentiate progressive from non-progressive lesions. VHL patients with at least one measurable hemangioblastoma were eligible. An intravenous injection with 37MBq (89)Zr-bevacizumab was administered 4 days before the scan. Maximum standardized uptake values were calculated. PET-scans were fused with routine magnetic resonance imaging (MRI) of the central nervous ...
Asco Meeting Abstracts, May 20, 2012
Ejc Suppl, 2010
A major challenge in cancer drug development is early selection of most promising drug candidate(... more A major challenge in cancer drug development is early selection of most promising drug candidate(s) for a specific target and to identify the patient (sub)populations most likely to benefit from such a drug. Therefore there is a need for techniques that can rapidly and precisely elucidate the pharmacokinetic and pharmacodynamic profile of new drugs in patients, and for (predictive) biomarkers of antitumor drug efficacy. Molecular imaging can potentially fulfill all these tasks and can be performed with several modalities, including magnetic resonance imaging, optical imaging, and radionuclide imaging with positron emission tomography (PET) or single photon emission computed tomography (SPECT). Most clinical molecular imaging data are gathered on the visualization of general processes, such as glucose metabolism and DNA synthesis with [ 18 F]fluorodeoxyglucose (FDG) and [ 18 F]fluoro-L-thymidine (FLT) PETimaging, respectively. Molecular imaging can also visualize tumor cell characteristics that are relevant for treatment, like hormone receptors, growth factors and growth factor receptors. It potentially provides serial non-invasive information about the status of these characteristics within the tumor and across lesions in the entire body. PET imaging of the estrogen receptor (ER) with 18 F-fluoro-17-b-estradiol (FES) proved feasible in breast cancer patients, whereas the androgen receptor (AR) was successfully imaged with 18 F-fluoro-5a-dihydrotestosterone (FDHT) in prostate cancer patients. FDHT-PET showed that MDV3100, an AR antagonist that blocks androgens from binding to the AR, substantially reduced FDHT binding (Scher et al, Lancet 2010). We imaged HER2 in metastatic breast cancer patients with 111 Intrastuzumab SPECT and 89 Zr-trastuzumab PET. 89 Zr-trastuzumab showed quantifiable tumor uptake and provided new insights in trastuzumab pharmacokinetics. 111 In-bevacizumab SPECT and 89 Zr-bevacizumab PET visualized VEGF in lesions of several tumor types. SPECT imaging of the TRAIL-R1 with 111 In-mapatumumab showed variable tumor uptake between patients. HER2 and VEGF-PET proved an excellent read out of downregulation of HER2 and VEGF by HSP90 inhibitors and of VEGF by mTOR inhibitors in xenograft mouse models. Preclinical VEGF imaging provided insights in the heterogeneous vascular tumor responses to sunitinib. These observations are now tested in clinical trials. Preclinical HER2-PET imaging showed decreased tumor tracer uptake after lapatinib treatment, due to inhibition of tracer internalization. Thus, new molecular imaging can identify the levels of a specific tumor target across the entire body over time, can provide new mechanistic and pharmacological insight and can contribute to development and selection of drug candidates and distinguish patients most likely to benefit from the treatment.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinom... more No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinoma (mRCC) exist. Tumor vascular endothelial growth factor A (VEGF-A) level may be useful. We determined tumor uptake of (89)Zr-bevacizumab, a VEGF-A-binding PET tracer, in mRCC patients before and during antiangiogenic treatment in a pilot study. Patients underwent (89)Zr-bevacizumab PET scans at baseline and 2 and 6 wk after initiating either bevacizumab (10 mg/kg every 2 wk) with interferon-α (3-9 million IU 3 times/wk) (n = 11) or sunitinib (50 mg daily, 4 of every 6 wk) (n = 11). Standardized uptake values were compared with plasma VEGF-A and time to disease progression. (89)Zr-bevacizumab PET scans visualized 125 evaluable tumor lesions in 22 patients, with a median SUV(max) (maximum standardized uptake value) of 6.9 (range, 2.3-46.9). Bevacizumab/interferon-α induced a mean change in tumor SUV(max) of -47.0% (range, -84.7 to +20.0%; P < 0.0001) at 2 wk and an additional -9.7% (ra...
Nederlands tijdschrift voor geneeskunde, 2011
Testicular carcinoma is a rare tumour but the most frequently occurring form of cancer in men age... more Testicular carcinoma is a rare tumour but the most frequently occurring form of cancer in men aged 18-35 years. In metastatic disease, following orchidectomy three or four courses of combination chemotherapy with cisplatin are given. With a general chance of cure of 80-90%, testicular cancer is still regarded as a model for a form of cancer that is curable. Due to this favourable prognosis--and to its rising incidence--the group of people who survive testicular cancer is growing and more attention is being paid to the risk of adverse consequences of treatment: secondary tumours and cardiovascular morbidity. Shared care follow-up for testicular cancer survivors with participation of both primary and secondary care is currently developed.
The Lancet Oncology, 2010
The metabolic syndrome, as a cluster of cardiovascular risk factors, may represent an important c... more The metabolic syndrome, as a cluster of cardiovascular risk factors, may represent an important connection between cancer treatment and its common late eff ect of cardiovascular disease. Insight into the aetiology of the metabolic syndrome after cancer treatment might help to identify and treat cancer survivors with increased cardiovascular risk. In this review, we summarise current knowledge on the prevalence and pathophysiology of the metabolic syndrome in cancer survivors, and discuss current intervention strategies with an emphasis on new developments.
Journal of Nuclear Medicine, 2014
Everolimus increases progression-free survival in patients with advanced neuroendocrine tumors (N... more Everolimus increases progression-free survival in patients with advanced neuroendocrine tumors (NETs). Currently, no biomarkers are available for early selection of patients who will benefit from everolimus. Everolimus can reduce vascular endothelial growth factor A (VEGF-A) production by tumor cells. Therefore, we aimed to investigate the effect of everolimus on tumor uptake of the radioactive-labeled VEGF-A antibody bevacizumab with PET in NET patients. Methods: Patients with advanced progressive well-differentiated NETs underwent 89 Zr-bevacizumab PET scans before and at 2 and 12 wk during everolimus treatment. 89 Zr-bevacizumab uptake was quantified by the maximum standardized uptake value (SUV max ). Tumor response and the percentage change in the sum of target lesion diameters were determined according to Response Evaluation Criteria in Solid Tumors 1.1 on CT (3 monthly). Results: In 4 of the 14 patients entered, no tumor lesions were visualized with 89 Zr-bevacizumab PET. In the remaining patients, 19% of tumor lesions 1 cm or greater known by CT were visualized. Tumor SUV max decreased during everolimus treatment, with a median of −7% at 2 wk (P 5 0.09) and a median of −35% at 12 wk (P , 0.001). The difference in SUV max at 2 and 12 wk with respect to SUV max at baseline correlated with percentage change on CT at 6 mo (r 2 5 0.51, P , 0.05, and r 2 5 0.61, P , 0.01, respectively). Conclusion: This study demonstrates variable 89 Zr-bevacizumab PET tumor uptake in NET patients. 89 Zr-bevacizumab tumor uptake diminished during everolimus treatment. Serial 89 Zr-bevacizumab PET might be useful as an early predictive biomarker of anti-VEGFdirected treatment in NET patients.
Cancer Research, 2011
Non-invasive imaging of angiogenesis could ease the optimization of antiangiogenesis treatments f... more Non-invasive imaging of angiogenesis could ease the optimization of antiangiogenesis treatments for cancer. In this study, we evaluated the role of VEGF-PET as a biomarker of dynamic angiogenic changes in tumors following treatment with the kinase inhibitor sunitinib. The effects of sunitinib treatment and withdrawal on the tumor was investigated using the new VEGF-PET tracer (89)Zr-ranibizumab as well as (18)F-FDG PET, and (15)O-water PET in mouse xenograft models of human cancer. The obtained imaging results were compared with tumor growth, VEGF plasma levels and immunohistologic analyzes. In contrast to (18)F-FDG and (15)O-water PET, VEGF-PET demonstrated dynamic changes during sunitinib treatment within the tumor with a strong decline in signal in the tumor center and only minimal reduction in tumor rim, with a pronounced rebound after sunitinib discontinuation. VEGF-PET results corresponded with tumor growth and immunohistochemical vascular- and tumor- markers. Our findings highlight the strengths of VEGF-PET imaging to allow serial analysis of angiogenic changes in different areas within a tumor.
Health expectations : an international journal of public participation in health care and health policy, Jan 15, 2017
Audit and feedback on professional practice and health care outcomes are the most often used inte... more Audit and feedback on professional practice and health care outcomes are the most often used interventions to change behaviour of professionals and improve quality of health care. However, limited information is available regarding preferred feedback for patients, professionals and health insurers. Investigate the (differences in) preferences of receiving feedback between stakeholders, using the Dutch Head and Neck Audit as an example. A total of 37 patients, medical specialists, allied health professionals and health insurers were interviewed using semi-structured interviews. Questions focussed on: "Why," "On what aspects" and "How" do you prefer to receive feedback on professional practice and health care outcomes? All stakeholders mentioned that feedback can improve health care by creating awareness, enabling self-reflection and reflection on peers or colleagues, and by benchmarking to others. Patients prefer feedback on the actual professional pract...
International journal of radiation oncology, biology, physics, Jan 6, 2017
We sought to assess the effect of age on overall survival (OS), cancer-specific survival (CSS), a... more We sought to assess the effect of age on overall survival (OS), cancer-specific survival (CSS), and non-cancer-related death (NCRD) in elderly (aged ≥70 years) head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radiation therapy. The results were compared with those of younger patients, and the most important prognostic factors for survival endpoints were determined. Treatments may be better justified based on identification of the main differences in survival between young and elderly patients. Data were analyzed from all consecutive HNSCC patients treated with definitive radiation therapy (66-70 Gy) in our department between April 2007 and December 2014. A total of 674 patients, including 168 elderly patients (24.9%), were included in the study. Multivariate association models were constructed to assess the effect of age on survival endpoints. Multivariate analysis was performed to identify potential prognostic factors for survival in elderly patients. ...
Journal of Nuclear Medicine, 2017
Currently, biomarkers that predict efficacy of everolimus in metastatic renal cell carcinoma (mRC... more Currently, biomarkers that predict efficacy of everolimus in metastatic renal cell carcinoma (mRCC) patients are lacking. Everolimus inhibits vascular endothelial growth factor A (VEGF-A) expression. We performed PET scans in mRCC patients with (89)Zr-bevacizumab, a VEGF-A-binding antibody tracer. Aims were to determine change in tumor tracer uptake after start of everolimus and to explore if (89)Zr-bevacizumab PET can identify patients with early disease progression. (89)Zr-bevacizumab PET was done before and 2 and 6 weeks after start of everolimus 10 mg/day in mRCC patients. Routine CT scans were performed at baseline and every 3 months thereafter. Tumor tracer uptake was quantified using maximum Standardized Uptake Value (SUVmax). Endpoints were change in tumor tracer uptake and treatment response on CT after 3 months. Thirteen patients participated. Median SUVmax of 94 tumor lesions was 7.3 (range 1.6-59.5). Between patients, median tumor SUVmax varied up to 8-fold. After 2 weeks, median SUVmax was 6.3 (1.7-62.3) corresponding to a mean decrease of 9.1% (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Three patients discontinued everolimus early. At 6 weeks, a mean decrease in SUVmax of 23.4% compared to baseline was found in 70 evaluable lesions of 10 patients, with a median SUVmax of 5.4 (1.1-49.4, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). All 10 patients who continued treatment had stable disease at 3 months. Everolimus decreases (89)Zr-bevacizumab tumor uptake. Further studies are warranted to evaluate predictive value of (89)Zr-bevacizumab PET for everolimus antitumor efficacy.
Critical Issues in Head and Neck Oncology, 2016
Head & neck, Jan 10, 2016
There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermedia... more There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck. All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed. We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%. In 50 patients with surgically resected high- or intermediate-grade osteosarcoma of the head and neck younger than 75 years, univariate and multivariable analysis, adjusting for age and resection margins, showed that patients who had not received chemotherapy had a significantly higher risk of local recurrence (hazard ratio [HR] = 3.78 and 3.66, respectively). In patients younger than 75 years of age with surgically resected high- and intermediate-grade osteosarcoma of the head and neck, treatment with (neo-)adjuvant chemotherapy resulted in a significantly smaller risk of local...
Oral oncology, 2016
To compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus w... more To compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus weekly cisplatin during adjuvant radiotherapy for high-risk head and neck squamous cell carcinoma (HNSCC). Consecutive HNSCC patients with involved resection margins and/or extra-capsular extension in two tertiary cancer centers with different institutional practices were identified. Cumulative cisplatin dose was calculated and information on toxicity reviewed and compared between patients who received 3-weekly versus weekly cisplatin. Of 270 high risk patients, 60 received 3-weekly 100mg/m(2) and 48 received weekly 50mg/m(2) cisplatin during adjuvant radiotherapy (60-66Gy in 30-33 fractions). Fourteen patients received other chemotherapy schedules and 148 received no chemotherapy. Mean cumulative cisplatin dose was 199.4mg/m(2) (standard error (SE) 5.4) in 3-weekly versus 239.8mg/m(2) (SE 11.0, P=0.001) in weekly treated patients. Cumulative cisplatin ⩾200mg/m(2) was given to 67.7% of pa...
The oncologist, Jan 21, 2016
In metastatic testicular cancer patients treated with bleomycin, etoposide, and cisplatin (BEP) c... more In metastatic testicular cancer patients treated with bleomycin, etoposide, and cisplatin (BEP) chemotherapy, bleomycin-induced pneumonitis is a well-known and potentially fatal side effect. We sought to determine the prevalence of lesions as signs of bleomycin-induced pulmonary changes on restaging computed tomography (CT) scans after treatment and to ascertain whether fibrosis markers were predictive of these changes. This prospective nonrandomized cohort study included metastatic testicular cancer patients, 18-50 years of age, treated with BEP chemotherapy. Restaging CT scans were examined for lesions as signs of bleomycin-induced pulmonary changes by two independent radiologists and graded as minor, moderate, or severe. Plasma samples were collected before, during, and after treatment and were quantified for transforming growth factor-β1 (TGF-β1), growth differentiation factor-15 (GDF-15), and high-sensitivity C-reactive protein (hs-CRP). In total, 66 patients were included: For...
Plos One, 2014
Background: Curative radiotherapy or chemoradiation for head and neck cancer (HNC) may result in ... more Background: Curative radiotherapy or chemoradiation for head and neck cancer (HNC) may result in severe acute and late side effects, including tube feeding dependence. The purpose of this prospective cohort study was to develop a prediction model for tube feeding dependence 6 months (TUBE M6 ) after curative (chemo-) radiotherapy in HNC patients. Patients and Methods: Tube feeding dependence was scored prospectively. To develop the multivariable model, a group LASSO analysis was carried out, with TUBE M6 as the primary endpoint (n = 427). The model was then validated in a test cohort (n = 183). The training cohort was divided into three groups based on the risk of TUBE M6 to test whether the model could be extrapolated to later time points (12, 18 and 24 months).
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 12, 2016
Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth ... more Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor (VEGF)-A produced locally is supposed to play an important role in development of disease manifestations and is a target for antiangiogenic therapy with the monoclonal antibody bevacizumab. We aimed to assess whether VHL manifestations can be visualized with 89Zirconium-bevacizumab positron emission tomography ((89)Zr-bevacizumab PET) and to explore whether (89)Zr-bevacizumab PET can differentiate progressive from non-progressive lesions. VHL patients with at least one measurable hemangioblastoma were eligible. An intravenous injection with 37MBq (89)Zr-bevacizumab was administered 4 days before the scan. Maximum standardized uptake values were calculated. PET-scans were fused with routine magnetic resonance imaging (MRI) of the central nervous ...
Asco Meeting Abstracts, May 20, 2012
Familial cancer, Jan 26, 2016
Central nervous system hemangioblastomas occur sporadically and in patients with von Hippel-Linda... more Central nervous system hemangioblastomas occur sporadically and in patients with von Hippel-Lindau (VHL) disease due to a VHL germline mutation. This mutation leads to enhanced transcription of chemokine receptor 4 (CXCR4), its ligand (CXCL12) and vascular endothelial growth factor A (VEGFA). We aimed to determine in VHL-related and sporadic hemangioblastomas CXCR4, CXCL12, and VEGFA protein expression and to correlate this to hemangioblastoma size and expression in normal surrounding tissue. 27 patients with a hemangioblastoma were included for analysis of immunohistochemistry of tissue, MRI and DNA. Hemangioblastomas overexpress CXCR4, CXCL12, and VEGFA compared to normal surrounding tissue. In sporadic hemangioblastomas the mean percentage of CXCR4 positive hemangioblastoma cells was 16 %, SD 8.4, in VHL-related hemangioblastomas 8 %, SD 4.4 (P = 0.002). There was no relation between preoperative tumor size and CXCR4 or CXCL12 expression. Compared to normal surrounding tissue CXC...
Oncotarget, Jan 14, 2016
Vascular endothelial growth factor (VEGF) pathway targeting agents have been combined with other ... more Vascular endothelial growth factor (VEGF) pathway targeting agents have been combined with other anticancer drugs, leading to improved efficacy in carcinoma of the cervix, stomach, lung, colon and rectum, ovary, and breast. Vessel normalization induced by VEGF pathway targeting agents influences tumor drug uptake. Following bevacizumab treatment, preclinical and clinical studies have shown a decrease in tumor delivery of radiolabeled antibodies and two chemotherapeutic drugs. The decrease in vessel pore size during vessel normalization might explain the decrease in tumor drug uptake. Moreover, the addition of bevacizumab to cetuximab, or panitumumab in colorectal cancer patients or to trastuzumab in breast cancer patients, did not improve efficacy. However, combining bevacizumab with chemotherapy did increase efficacy in some cancer types. Novel biomarkers to select patients who may benefit from combination therapies, such as the effect of an angiogenesis inhibitor on tumor perfusio...