Geke A P Hospers

University of Groningen, Groningen, Groningen, Netherlands

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Publications (102)438.43 Total impact

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    ABSTRACT: Whereas anti-oestrogen therapy is widely applied to treat oestrogen receptor (ER) positive breast cancer, paradoxically, oestrogens can also induce tumour regression. Up-regulation of ER expression is a marker for oestrogen hypersensitivity. We, therefore, performed an exploratory study to evaluate positron emission tomography (PET) with the tracer 16α-[(18)F]fluoro-17β-oestradiol ((18)F-FES) as potential marker to select breast cancer patients for oestradiol therapy. Eligible patients had acquired endocrine-resistant metastatic breast cancer that progressed after ≥2 lines of endocrine therapy. All patients had prior ER-positive histology. Treatment consisted of oestradiol 2 mg, three times daily, orally. Patients underwent (18)F-FES-PET/CT imaging at baseline. Tumour (18)F-FES-uptake was quantified for a maximum of 20 lesions and expressed as maximum standardised uptake value (SUVmax). CT-scan was repeated every 3 months to evaluate treatment response. Clinical benefit was defined as time to radiologic or clinical progression ≥24 weeks. (18)F-FES uptake, quantified for 255 lesions in 19 patients, varied greatly between lesions (median 2.8; range 0.6-24.3) and between patients (median 2.5; range 1.1-15.5). Seven (37 %) patients experienced clinical benefit of oestrogen therapy, eight progressed (PD), and four were non-evaluable due to side effects. The positive and negative predictive value (PPV/NPV) of (18)F-FES-PET for response to treatment were 60 % (95 % CI: 31-83 %) and 80 % (95 % CI: 38-96 %), respectively, using SUVmax >1.5. (18)F-FES-PET may aid identification of patients with acquired antihormone resistant breast cancer that are unlikely to benefit from oestradiol therapy.
    European Journal of Nuclear Medicine 06/2015; DOI:10.1007/s00259-015-3107-5 · 5.22 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the effect on the number of performed biopsies and costs associated with implementing positron emission tomography (PET) and computed tomography (PET/CT) with 16α-[(18)F]fluoro-17β-oestradiol (FES) or 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) as an upfront imaging test for diagnosing metastatic breast cancer (MBC) in comparison with the standard work-up in oestrogen receptor-positive women with symptoms. A published computer simulation model was adapted and validated. Three follow-up strategies were evaluated in a simulated cohort of women with primary breast cancer over a 5-year-time horizon: (1) the standard work-up, (2) upfront FES-PET/CT and (3) upfront FDG-PET/CT. The main outcome was the number of avoided biopsies to assess MBC. The costs for all three strategies were calculated based on the number of imaging tests and biopsies. The incremental cost-effectiveness ratio (ICER) to avoid a biopsy was calculated only based on the costs of initial imaging and staging tests. The FES-PET/CT strategy decreased the number of biopsies by 39±9%, while upfront FDG-PET/CT increased the number of biopsies by 38±15% when compared with the standard work-up. Both PET/CT strategies reduced the number of imaging tests and false positives when compared with the standard work-up. The number of false negatives decreased only in the FES-PET/CT strategy. The ICER in the FES-PET/CT strategy per avoided biopsy was 12.1±3.4 thousand Euro. In the FDG-PET/CT strategy, the costs were higher and there were no avoided biopsies as compared with the standard work-up, hence this was an inferior strategy in terms of cost effectiveness. The number of performed biopsies was lower in the FES-PET/CT strategy at an ICER of 12.1±3.4 thousand Euro per biopsy avoided, whereas the application of the FDG-PET/CT did not reduce the number of biopsies and was more expensive. Whether the FES-PET/CT strategy has additional benefits for patients in terms of therapy management has to be evaluated in clinical studies.British Journal of Cancer advance online publication 16 April 2015. doi:10.1038/bjc.2015.138 www.bjcancer.com.
    British Journal of Cancer 04/2015; 112(10). DOI:10.1038/bjc.2015.138 · 4.82 Impact Factor
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    ABSTRACT: Metastatic rectal cancer patients could benefit from novel therapeutic approaches. The signaling network formed by chemokines and their receptors can promote metastasis and resistance to current anticancer treatments. This study assessed the expression of chemokine receptor 4 (CXCR4) and its ligand CXCL12 immuhistochemically in stage IV rectal tumors. Paraffin-embedded primary tumor collected before and after local radiotherapy and systemic treatment with bevacizumab, oxaliplatin and capecitabine was analyzed. Receptor and ligand expression was assessed in the cytoplasm and nucleus of tumor, stromal and normal rectal crypt cells. Baseline expression of CXCR4 and CXCL12 was correlated with patients' pathologic response to treatment. At diagnosis (n=46), 89% of the rectal tumors expressed cytoplasmic CXCR4 and 81% CXCL12. Nuclear CXCR4 expression in tumor cells was present in 30% and nuclear CXCL12 expression in 35% of the tumors. After radiochemotherapy and bevacizumab, nuclear CXCL12 expression was present in 79% of residual tumors, as compared to 31% of the paired tumor samples expressing nuclear CXCL12 before treatment (P=0.001). There were no differences in CXCR4 or CXCL12 expression at baseline between the patients that had (n=9) and did not have (n=30) a pathologic complete response. Our results show that CXCR4 and CXCL12 are extensively expressed in primary rectal tumors of patients presenting with metastatic disease, while radiochemotherapy and bevacizumab further upregulate CXCL12 expression. These data indicate the importance of the CXCR4/CXCL12 axis in rectal tumor biology, and may suggest the CXCR4/CXCL12 receptor-ligand pair as a potential therapeutic target in metastatic rectal cancer.
  • Radiotherapy and Oncology 12/2014; 111:S97-S98. DOI:10.1016/S0167-8140(15)30359-5 · 4.86 Impact Factor
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    ABSTRACT: The estrogen receptor (ER) α is expressed in ~70% of ovarian cancer tumors. Positron emission tomography (PET) of tumor ERα expression with the tracer 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) may be valuable to select ovarian cancer patients for endocrine therapy. The aim of this study was to evaluate the feasibility of (18)F-FES-PET to determine tumor ERα expression non-invasively in epithelial ovarian cancer patients. (18)F-FES-PET/CT was performed shortly before cytoreductive surgery. Tumor (18)F-FES uptake was quantified for all lesions ≥10 mm on CT and expressed as maximum standardized uptake value (SUVmax). (18)F-FES-PET/CT findings were compared to histology and immunohistochemistry for ERα, ERβ, and progesterone receptor (PR). Receptor expression was scored semi-quantitatively using H-scores (percentage of positive tumor cells x staining intensity). The optimum threshold to discriminate ER-positive and negative lesions was determined by receiver operating characteristic analysis. In the 15 included patients with suspected ovarian cancer, 32 measurable lesions >10 mm were present on CT. Tumor (18)F-FES uptake could be quantified for 28 lesions (88%), four lesions were visible but non-quantifiable due to high uptake in adjacent tissue. During surgery, histology was obtained of 23 out of 28 quantified lesions (82%). Quantitative (18)F-FES uptake correlated with the semi-quantitative immunoscore for ERα (ρ = 0.65, P < 0.01), weakly with PR expression (ρ = 0.46, P = 0.03) and was not associated with ERβ expression (ρ = 0.21, P = 0.33). The optimal threshold to discriminate ERα-positive and ERα-negative lesions was a SUVmax >1.8, which provided a 79% sensitivity, 100% specificity, and area under the curve of 0.86 (95% CI 0.70-1.00). In two of seven patients with cytology/histology available at primary diagnosis and at debulking surgery immunohistochemical ERα expression had changed over time. (18)F-FES-PET was in accordance with histology at debulking surgery, but not at primary diagnosis, indicating that (18)F-FES-PET can provide reliable information about current tumor ERα status. (18)F-FES-PET/CT can reliably assess ERα status in epithelial ovarian cancer tumors and metastases non-invasively. Evaluation of the predictive value of (18)F-FES-PET/CT for endocrine therapy in epithelial ovarian cancer patients is warranted. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 12/2014; DOI:10.2967/jnumed.114.147579 · 5.56 Impact Factor
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    ABSTRACT: The aim of this prospective study was to determine the proportion of locoregional recurrences (LRRs) that could have been prevented if radiotherapy treatment planning for oesophageal cancer was based on PET/CT instead of CT. Ninety oesophageal cancer patients, eligible for high dose (neo-adjuvant) (chemo)radiotherapy, were included. All patients underwent a planning FDG-PET/CT-scan. Radiotherapy target volumes (TVs) were delineated on CT and patients were treated according to the CT-based treatment plans. The PET images remained blinded. After treatment, TVs were adjusted based on PET/CT, when appropriate. Follow up included CT-thorax/abdomen every 6months. If LRR was suspected, a PET/CT was conducted and the site of recurrence was compared to the original TVs. If the LRR was located outside the CT-based clinical TV (CTV) and inside the PET/CT-based CTV, we considered this LRR possibly preventable. Based on PET/CT, the gross tumour volume (GTV) was larger in 23% and smaller in 27% of the cases. In 32 patients (36%), >5% of the PET/CT-based GTV would be missed if the treatment planning was based on CT. The median follow up was 29months. LRRs were seen in 10 patients (11%). There were 3 in-field recurrences, 4 regional recurrences outside both CT-based and PET/CT-based CTV and 3 recurrences at the anastomosis without changes in TV by PET/CT; none of these recurrences were considered preventable by PET/CT. No LRR was found after CT-based radiotherapy that could have been prevented by PET/CT. The value of PET/CT for radiotherapy seems limited. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Radiotherapy and Oncology 11/2014; 113(2). DOI:10.1016/j.radonc.2014.10.016 · 4.86 Impact Factor
  • Frederik H E Schagen, Rob C Hoeben, Geke A P Hospers
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    ABSTRACT: Abstract Recently, the first human medicine containing a genetically modified organism (GMO medicine) was authorized for use in the European market. Just as any medicinal product, the market authorization for a GMO medicine contains a precise description of the therapeutic use for which the medicinal product is intended. Within this use, the application of the GMO medicine is permitted, without the need for the institution to obtain a specific permit. In practice, however, medicinal products are also frequently prescribed for treatment outside the registered therapeutic use, a practice that is referred to as "off-label use." While off-label use of conventional medicines is permitted and has been very useful, the off-label use of GMO medicines is not covered in the European Union (EU) legislation or guidelines and falls under each member state's national environmental legislation. This implies that in the Netherlands and most other EU member states, an environmental permit will be required for any institution that uses the GMO medicine outside the registered application(s). In the Netherlands, this permit is identical to the permits required for the execution of clinical trials involving nonregistered GMOs. The application procedure for such permit is time-consuming. This process can therefore limit the therapeutic options for medical professionals. As a consequence, desired treatment regimens could be withheld for certain patient (groups). To make future off-label use of GMO medicines permissible in a way that is acceptable for all stakeholders, regulators should adopt a proactive attitude and formulate transparent legislative procedures for this. Only then the field can maintain the public acceptance of GMO medicines, while maintaining the freedom to operate of medical professionals.
    Human Gene Therapy 10/2014; 25(10):893-896. DOI:10.1089/hum.2014.090 · 3.62 Impact Factor
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    ABSTRACT: Locally advanced rectal cancer is customarily treated with neoadjuvant chemoradiotherapy (CRT) followed by a total mesorectal excision. During the course of CRT, previously non-detectable distant metastases can appear. Therefore, a restaging CT scan of the chest and abdomen was performed prior to surgery. The aim of this study was to determine the frequency of a change in treatment strategy after this restaging CT scan.
    Annals of Surgical Oncology 08/2014; DOI:10.1245/s10434-014-3996-8 · 3.94 Impact Factor
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    ABSTRACT: Background Neoadjuvant chemoradiotherapy (CRT) in esophageal cancer (EC) patients may increase the formation of thromboembolic events (TEE’s). We analyzed the incidence and impact of TEE’s in EC patients treated with platinum-based CRT. Patient and methods A total of 336 patients with EC underwent an esophagectomy of which 110 patients received neoadjuvant CRT (41.4Gy with concurrent Carboplatin/Paclitaxel). Patients were matched based on pre- and perioperative characteristics. Results Preoperatively, 9 (8.2%) patients with neoadjuvant CRT (p=0.004) were diagnosed with TEE’s. Despite delay until surgery (p=0.021), the postoperative course did not differ. In multivariate analysis, a history of DVT (p=0.005) and neoadjuvant CRT (p=0.004) were identified as risk factors. Postoperatively, there was no differences in TEE’s (p=0.560) observed. In multivariate analysis, a history of pulmonary embolism (p=0.012) was identified as risk factor for postoperative TEE’s. Conclusion Preoperatively, EC patients treated with neoadjuvant CRT have an increased risk to develop a TEE, especially those with a previous history of TEE. After surgery no increased incidence was observed. We recommend secondary prophylaxis during neoadjuvant treatment in this high-risk group.
    American journal of surgery 08/2014; 208(2). DOI:10.1016/j.amjsurg.2013.10.031 · 2.41 Impact Factor
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    ABSTRACT: This study was initiated to investigate the feasibility and efficacy of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally advanced gastric cancer.
    Radiotherapy and Oncology 05/2014; 112(2). DOI:10.1016/j.radonc.2014.05.003 · 4.86 Impact Factor
  • Oncology (Williston Park, N.Y.) 05/2014; 28(5):434-6. · 2.98 Impact Factor
  • Journal of Clinical Oncology 04/2014; DOI:10.1200/JCO.2013.51.4471 · 17.88 Impact Factor
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    ABSTRACT: Methods Patients with advanced cutaneous melanoma were treated in the netherlands (nl) and the United King-dom (UK) with ipilimumab at 3 mg/kg. Baseline charac-teristics and peripheral blood parameters were assessed, and patients were monitored for the occurrence of adverse events and outcomes. Results a total of 166 patients were treated in the neth-erlands. Best overall response and disease control rates were 17 and 35 %, respectively. Median follow-up was 17.9 months, with a median progression-free survival of 2.9 months. Median OS was 7.5 months, and OS at 1 year was 37.8 % and at 2 years was 22.9 %. In a multivariate model, baseline serum lactate dehydrogenase (lDH) was demonstrated to be the strongest predictive factor for OS. Abstract Introduction Ipilimumab, a cytotoxic t lymphocyte-associated antigen-4 blocking antibody, has improved over-all survival (OS) in metastatic melanoma in phase III tri-als. However, about 80 % of patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a 'real world' population of patients treated with ipilimumab to identify markers for treatment benefit.
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    ABSTRACT: Ipilimumab, a cytotoxic T lymphocyte-associated antigen-4 blocking antibody, has improved overall survival (OS) in metastatic melanoma in phase III trials. However, about 80 % of patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a 'real world' population of patients treated with ipilimumab to identify markers for treatment benefit. Patients with advanced cutaneous melanoma were treated in the Netherlands (NL) and the United Kingdom (UK) with ipilimumab at 3 mg/kg. Baseline characteristics and peripheral blood parameters were assessed, and patients were monitored for the occurrence of adverse events and outcomes. A total of 166 patients were treated in the Netherlands. Best overall response and disease control rates were 17 and 35 %, respectively. Median follow-up was 17.9 months, with a median progression-free survival of 2.9 months. Median OS was 7.5 months, and OS at 1 year was 37.8 % and at 2 years was 22.9 %. In a multivariate model, baseline serum lactate dehydrogenase (LDH) was demonstrated to be the strongest predictive factor for OS. These findings were validated in an independent cohort of 64 patients from the UK. In both the NL and UK cohorts, long-term benefit of ipilimumab treatment was unlikely for patients with baseline serum LDH greater than twice the upper limit of normal. In the absence of prospective data, clinicians treating melanoma may wish to consider the data presented here to guide patient selection for ipilimumab therapy.
    Cancer Immunology and Immunotherapy 03/2014; DOI:10.1007/s00262-014-1528-9 · 3.94 Impact Factor
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    ABSTRACT: Methods Patients with advanced cutaneous melanoma were treated in the netherlands (nl) and the United King-dom (UK) with ipilimumab at 3 mg/kg. Baseline charac-teristics and peripheral blood parameters were assessed, and patients were monitored for the occurrence of adverse events and outcomes. Results a total of 166 patients were treated in the neth-erlands. Best overall response and disease control rates were 17 and 35 %, respectively. Median follow-up was 17.9 months, with a median progression-free survival of 2.9 months. Median OS was 7.5 months, and OS at 1 year was 37.8 % and at 2 years was 22.9 %. In a multivariate model, baseline serum lactate dehydrogenase (lDH) was demonstrated to be the strongest predictive factor for OS. Abstract Introduction Ipilimumab, a cytotoxic t lymphocyte-associated antigen-4 blocking antibody, has improved over-all survival (OS) in metastatic melanoma in phase III tri-als. However, about 80 % of patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a 'real world' population of patients treated with ipilimumab to identify markers for treatment benefit.
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    ABSTRACT: The orally available BRAF kinase inhibitor vemurafenib, compared with dacarbazine, shows improved response rates, progression-free survival (PFS), and overall survival in patients with metastatic melanoma that has a BRAF(V600) mutation. We assessed vemurafenib in patients with advanced metastatic melanoma with BRAF(V600) mutations who had few treatment options. In an open-label, multicentre study, patients with untreated or previously treated melanoma and a BRAF(V600) mutation received oral vemurafenib 960 mg twice a day. The primary endpoint was safety. All analyses were done on the safety population, which included all patients who received at least one dose of vemurafenib. This report is the third interim analysis of this study. This study is registered with ClinicalTrials.gov, number NCT01307397. Between March 1, 2011, and Jan 31, 2013, 3226 patients were enrolled in 44 countries. 3222 patients received at least one dose of vemurafenib (safety population). At data cutoff, 868 (27%) patients were on study treatment and 2354 (73%) had withdrawn, mainly because of disease progression. Common adverse events of all grades included rash (1592 [49%]), arthralgia (1259 [39%]), fatigue (1093 [34%]), photosensitivity reaction (994 [31%]), alopecia (826 [26%]), and nausea (628 [19%]). 1480 (46%) patients reported grade 3 or 4 adverse events, including cutaneous squamous cell carcinoma (389 [12%]), rash (155 [5%]), liver function abnormalities (165 [5%]), arthralgia (106 [3%]), and fatigue (93 [3%]). Grade 3 and 4 adverse events were reported more frequently in patients aged 75 years and older (n=257; 152 [59%, 95% CI 53-65] and ten [4%, 2-7], respectively) than in those younger than 75 years (n=2965; 1286 [43%, 42-45] and 82 [3%, 2-3], respectively). Vemurafenib safety in this diverse population of patients with BRAF(V600) mutated metastatic melanoma, who are more representative of routine clinical practice, was consistent with the safety profile shown in the pivotal trials of this drug. F Hoffmann-La Roche.
    The Lancet Oncology 02/2014; 15(4). DOI:10.1016/S1470-2045(14)70051-8 · 24.73 Impact Factor
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    ABSTRACT: In esophageal cancer (EC) patients who are not eligible for surgery, definitive chemoradiation (dCRT) with curative intent using cisplatinum with 5-fluorouracil (5-FU) is the standard chemotherapy regimen. Nowadays carboplatin/paclitaxel is also often used. In this study, we compared survival and toxicity rates between both regimens. This multicenter study included 102 patients treated in five centers in the Northeast Netherlands from 1996 till 2008. Forty-seven patients received cisplatinum/5-FU (75 mg/m(2) and 1 g/m(2)) and 55 patients carboplatin/paclitaxel (AUC2 and 50 mg/m(2)). Overall survival (OS) was not different between the cisplatinum/5-FU and carboplatin/paclitaxel group {[P = 0.879, hazard ratio (HR) 0.97 [confidence interval (CI) 0.62-1.51]}, with a median survival of 16.1 (CI 11.8-20.5) and 13.8 months (CI 10.8-16.9). Median disease-free survival (DFS) was comparable [P = 0.760, HR 0.93 (CI 0.60-1.45)] between the cisplatinum/5-FU group [11.1 months (CI 6.9-15.3)] and the carboplatin/paclitaxel group [9.7 months (CI 5.1-14.4)]. Groups were comparable except clinical T stage was higher in the carboplatin/paclitaxel group (P = 0.008). High clinical T stage (cT4) was not related to OS and DFS in a univariate analysis (P = 0.250 and P = 0.201). A higher percentage of patients completed the carboplatin/paclitaxel regimen (82% versus 57%, P = 0.010). Hematological and nonhematological toxicity (≥grade 3) in the carboplatin/paclitaxel group (4% and 18%) was significantly lower than in the cisplatinum/5-FU (19% and 38%, P = 0.001). In this study, we showed comparable outcome, in terms of DFS and OS for carboplatin/paclitaxel compared with cisplatinum/5-FU as dCRT treatment in EC patients. Toxicity rates were lower in the carboplatin/paclitaxel group together with higher treatment compliance. Carboplatin/paclitaxel as an alternative treatment of cisplatinum/5-FU is a good candidate regimen for further evaluation.
    Annals of Oncology 02/2014; 25(3). DOI:10.1093/annonc/mdt589 · 6.58 Impact Factor
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    ABSTRACT: Objectives This study was initiated to investigate the feasibility and efficacy of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally advanced gastric cancer. Methods In a prospective study, patients with locally advanced gastric cancer stage IB-IV(M0) were treated with chemoradiotherapy followed by surgery 4–6 weeks after the last irradiation. Chemoradiotherapy consisted of radiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy, combined with concurrent weekly carboplatin and paclitaxel. Results Between December 2007 and January 2012, 25 patients with cT3 (64%) or cT4 (36%) gastric cancer were included. One patient discontinued concurrent chemotherapy in the 4th week due to toxicity, but completed radiotherapy. Another patient discontinued chemoradiotherapy after the 3rd week due to progressive disease. Grade III adverse events of chemoradiotherapy were: gastrointestinal 12%, haematological 12% and other 8%. All patients, except one who developed progressive disease, were operated. Surgical complications were: general/infectious 48%, anastomotic leakage 12%, and bowel perforation 8%. Postoperative mortality was 4%. Microscopically radical resection rate was 72%. Pathological complete response rate was 16% and near complete response rate 24%. Conclusions In this study, preoperative chemoradiotherapy for patients with locally advanced gastric cancer was associated with manageable toxicity and encouraging pathological response rates.
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    ABSTRACT: Neoadjuvant chemoradiotherapy (CRT) improves locoregional control and overall survival in esophageal cancer patients. Although adverse events are relatively low during neoadjuvant CRT, severe postoperative adverse effects may occur, leading to morbidity and even mortality. We investigated the impact of a more frequently used neoadjuvant CRT regimen of 41.4 Gy/5 weeks radiotherapy with concurrent carboplatin and paclitaxel (CROSS schedule) on the postoperative course. Between 2006 and 2012, a total of 96 esophageal cancer patients (staged cT1N+/T2-4a/N0-3 and M0) were treated according to the above neoadjuvant scheme. To reduce bias in this single-center study, we performed a propensity score-matched analysis with patients who underwent surgery alone (n = 230) from a prospectively maintained database (n = 326). Baseline characteristics between both groups were equally distributed in the matched cohort. In the neoadjuvant treated group, significantly more patients were diagnosed with pneumonia (27.1 vs. 51.0 %; p = 0.001), pleural effusion (12.5 vs. 24.0 %; p = 0.040), and arrhythmia (20.4 vs. 34.4 %; p = 0.008). In addition, in the multivariate analysis, neoadjuvant CRT was significantly associated with an increased risk of pneumonia (p = 0.001, odds ratio 2.896), pleural effusion (p = 0.041, odds ratio 2.268), and arrhythmia (p = 0.023, odds ratio 2.215). Despite these outcomes, no differences were detected in duration of intensive care unit or hospital stay. Short-term mortality did not differ between both groups. We observed an increase of cardiopulmonary complications in the neoadjuvant CRT group, without any effect on hospital or intensive care unit stay and mortality. Further research is warranted on the limitation of chemoradiation-induced cardiopulmonary toxicity.
    Annals of Surgical Oncology 10/2013; 21(2). DOI:10.1245/s10434-013-3316-8 · 3.94 Impact Factor
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    ABSTRACT: Oestrogen receptors are overexpressed in around 70% of all breast cancers, and are a target for endocrine therapy. These receptors can be visualised on PET with use of 16α-[(18)F]-fluoro-17β-oestradiol ((18)F-FES) as a tracer. Compared with biopsy, which enables assessment of individual sites, whole-body (18)F-FES-PET enables quantification of oestrogen-receptor expression in all metastases. In several studies, measurement of tumour protein expression in oestrogen receptors by (18)F-FES-PET, concurrent with biopsy, detected oestrogen-receptor-positive tumour lesions with a sensitivity of 84% and specificity of 98%. Roughly 45% of patients with metastatic breast cancer have discordant oestrogen-receptor expression across lesions (ie, (18)F-FES-positive and (18)F-FES-negative metastases). Low tumour (18)F-FES uptake in metastases can predict failure of hormonal therapy in patients with oestrogen-receptor-positive primary tumours. Finally, (18)F-FES-PET has shown that oestrogen-receptor binding capacity changes after intervention with hormonal drugs, but findings need to be confirmed. Factors other than oestrogen-receptor expression, including menopausal status and concomitant therapies, that can affect tumour (18)F-FES uptake must be taken into account.
    The Lancet Oncology 10/2013; 14(11):e465-e475. DOI:10.1016/S1470-2045(13)70292-4 · 24.73 Impact Factor

Publication Stats

2k Citations
438.43 Total Impact Points

Institutions

  • 2002–2015
    • University of Groningen
      • • Department of Medical Oncology
      • • Department of Internal Medicine
      • • Department of Internal Medicine
      Groningen, Groningen, Netherlands
  • 1988–2014
    • Universitair Medisch Centrum Groningen
      • • Department of Internal Medicine
      • • Department of Cardiology
      Groningen, Groningen, Netherlands
  • 2005
    • Bethesda Hospital
      Hoogeveen, Drenthe, Netherlands
  • 2000
    • GGD Groningen
      Groningen, Groningen, Netherlands