New treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not... Show moreNew treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not included in pivotal trials. Therefore, we investigated treatment patterns and overall survival over time in older patients with metastatic colorectal cancer in a population-based study. We identified 22.192 Dutch patients aged & GE;70 years diagnosed with synchronous metastatic colorectal cancer between 2005 and 2020 from the Netherlands Cancer Registry. Changes in treatment over time were assessed with logistic regression models. Survival was assessed by Cox proportional hazard ratios (HR). Results showed that chemotherapy use increased between 2005 and 2015, but declined from 2015 onwards, while more patients received best supportive care. Over time, fewer patients underwent primary tumor resection alone. Although survival of both metastatic colon and rectal cancer improved until 2014, survival of colon cancer decreased from 2014 onwards (HR 1.04, 95% confidence interval [CI] 1.01-1.05), which was seen in all age groups. Survival of metastatic rectal cancer patients remained unchanged from 2014 onwards (HR 1.00, 95% CI 0.98-1.03) in all age groups. In conclusion, treatment patterns of Dutch older patients with synchronous metastatic colorectal cancer rapidly changed from 2005 to 2020, with increasing percentages of patients receiving best supportive care. Survival of metastatic colon cancer decreased from 2014 onwards. The implementation of a colorectal cancer screening program and patient selection might explain why only a subset of older patients seem to benefit from the availability of novel treatment options. Show less
Baltussen, J.C.; Glas, N.A. de; Liefers, G.J.; Slingerland, M.; Speetjens, F.M.; Bos, F. van den; ... ; Derks, M.G.M. 2023
New treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not... Show moreNew treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not included in pivotal trials. Therefore, we investigated treatment patterns and overall survival over time in older patients with metastatic colorectal cancer in a population-based study. We identified 22.192 Dutch patients aged ≥70 years diagnosed with synchronous metastatic colorectal cancer between 2005 and 2020 from the Netherlands Cancer Registry. Changes in treatment over time were assessed with logistic regression models. Survival was assessed by Cox proportional hazard ratios (HR). Results showed that chemotherapy use increased between 2005 and 2015, but declined from 2015 onwards, while more patients received best supportive care. Over time, fewer patients underwent primary tumor resection alone. Although survival of both metastatic colon and rectal cancer improved until 2014, survival of colon cancer decreased from 2014 onwards (HR 1.04, 95% confidence interval [CI] 1.01-1.05), which was seen in all age groups. Survival of metastatic rectal cancer patients remained unchanged from 2014 onwards (HR 1.00, 95% CI 0.98-1.03) in all age groups. In conclusion, treatment patterns of Dutch older patients with synchronous metastatic colorectal cancer rapidly changed from 2005 to 2020, with increasing percentages of patients receiving best supportive care. Survival of metastatic colon cancer decreased from 2014 onwards. The implementation of a colorectal cancer screening program and patient selection might explain why only a subset of older patients seem to benefit from the availability of novel treatment options. Show less
Background: Patients with osteosarcoma (OS) and Ewing sarcoma (ES) are considered to have a high venous thromboembolism (VTE) risk, although the exact incidence and prognostic impact are under... Show moreBackground: Patients with osteosarcoma (OS) and Ewing sarcoma (ES) are considered to have a high venous thromboembolism (VTE) risk, although the exact incidence and prognostic impact are under-researched in general as well as in relevant age groups. Aims: To study the impact of VTE and major bleeding (MB) in OS and ES patients, subdivided in children, Ad-olescents Young Adults (AYAs; aged 18-39) and older adults. Methods: Retrospective single-center chart review in 519 OS and 165 ES patients treated between 1980 and 2018. Patients were followed from sarcoma diagnosis until an outcome of interest (VTE, MB) or death occurred. Cu-mulative incidences were estimated with death as competing risk. Cox models were used to determine prognostic impact. Results: Five-year cumulative incidences of VTE were 12 % (95%CI 9.1-15) for OS and 6.7 % (95%CI 3.5-11) for ES patients, mostly happening in patients >= 18 years; the most frequent VTE presentation was catheter-related upper-extremity thrombosis (OS: 18/65, ES: 7/11). Five-year cumulative incidences for MB were 5.8 % (95% CI 4.0-8.1) in OS and 5.4 % (95%CI 2.5-9.8) in ES patients. 192 OS and 77 ES AYAs were included, who faced similar VTE and MB incidences as older adults. In OS, VTE and MB were both associated with mortality (adjusted HRs 2.0 [95%CI 1.4-2.9] and 2.4 [95%CI 1.4-4.0], respectively), whereas in ES this association was only present for MB (aHR 3.4 [95%CI 1.2-9.6]). Conclusions: VTE is a frequent complication in adult OS and to a lesser extent in ES patients, while the rate of MB was comparably high in both sarcoma types. Show less
This thesis describes several retrospective studies in mesenchymal tumours. Sarcomas are the malignant variant and are very rare with an incidence of approximately 1000 patients per year in the... Show moreThis thesis describes several retrospective studies in mesenchymal tumours. Sarcomas are the malignant variant and are very rare with an incidence of approximately 1000 patients per year in the Netherlands divided over more than 50 subtypes. It is essential to use the available patient data as much as possible.Due to its rarity, all stages of sarcomas are usually grouped in one study. This thesis shows that patients with distant metastatic disease have a worse prognosis compared to patients with locally advanced disease. To improve the prognosis of sarcoma patients, maintenance treatment after first line doxorubicin treatment is currently considered. However, we show that only 33% of the patients qualifies for maintenance treatment. Patients that qualify for maintenance treatment have a significantly better prognosis than all doxorubicin treated sarcoma patients.Further, this thesis describes several rare side effects and treatment for this side effect of treatment in mesenchymal tumours and it reports the incidences of giant cell tumours of bone and gastro-intestinal stromal tumours . It also studies the outcomes of non-surgical treatment options for desmoid-type fibromatosis. Last, the outcomes of ifosfamide treatment as second line treatment for osteosarcoma are reported. Show less
Verschoor, A.J.; Litiere, S.; Marreaud, S.; Judson, I.; Toulmonde, M.; Wardelmann, E.; ... ; Gelderblom, H. 2020
Background Doxorubicin based chemotherapy is standard first line treatment for patients with soft tissue sarcoma. Currently several options to improve survival after doxorubicin based chemotherapy... Show moreBackground Doxorubicin based chemotherapy is standard first line treatment for patients with soft tissue sarcoma. Currently several options to improve survival after doxorubicin based chemotherapy are being studied. This study reports on survival after completing 6 cycles of doxorubicin containing first line treatment, which is important when designing studies trying to improve outcomes of first line treatment. Methods A retrospective database analysis was performed on 2045 patients from 12 EORTC sarcoma trials (inclusion period 1980-2012) receiving first line doxorubicin based chemotherapy for advanced soft tissue sarcoma in order to establish progression free survival and overall survival after completing 6 cycles of first line doxorubicin based chemotherapy. Endpoints were overall survival and progression free survival. Factors studied were histologic subtype and type of doxorubicin chemotherapy. Results 748 of 2045 (36.6%) received at least 6 cycles and did not progress during or at the end of chemotherapy. 475 of 2045 (23.2%) of patients received exactly 6 cycles and did not progress during or at the end of chemotherapy. Median progression free survival after 6 cycles of doxorubicin based chemotherapy was 4.2 months (95% confidence interval 3.7-4.8) and median overall survival 15.7 months (14.0-17.8). Median progression free survival and overall survival from randomisation/registration were 8.7 months (95% confidence interval 8.2-9.1) and 20.1 months (95% confidence interval 18.3-22.3) respectively. Significant differences in progression free survival were found between chemotherapy regimens, but not for overall survival. These data are also reported for patients receiving 7 or more cycles of chemotherapy and for patients with 3 or more cycles of chemotherapy. Conclusion This large retrospective study is the first to report progression free survival and overall survival after completion of 6 cycles of first line doxorubicin containing chemotherapy. These results are important when designing new studies exploring for example maintenance therapy after doxorubicin based chemotherapy. Show less
Mass is traditionally the unique measure of the administered dose in toxicity studies with conventional chemical substances. Because of the variety of specific physical properties of nanoparticles,... Show moreMass is traditionally the unique measure of the administered dose in toxicity studies with conventional chemical substances. Because of the variety of specific physical properties of nanoparticles, other dose metrics such as the number of particles, their size, shape, surface area or volume may be more appropriate. Here we applied a systematic, unbiased approach to derive the most appropriate dose metric for nanoparticles from experimental data. The approach was exemplified for copper, zinc oxide, and silver nanoparticles with different diameters, coatings and shapes, combining experiments with six aquatic organisms, two mammalian and two piscine liver cell lines from different research groups. The nanoparticle diameter appeared to be a powerful estimator of metal oxide nanoparticle effects. Since effect concentrations were related to size to the power 3, it is indicated that volume (mass) is the appropriate dose metric for all tested species and toxicological endpoints and all tested metal oxide nanoparticles within the tested size range (25–500 nm). The new method enables extrapolation of test results from one type of metal oxide nanomaterial to another, thereby offering a powerful tool to improved efficiency in risk research and risk assessment of nanomaterials. Show less
Background: Home treatment of cancer-associated venous thromboembolism (VTE) is challenging due to thehigh risk of adverse events. While home treatment is quite agreeable to cancer patients,... Show moreBackground: Home treatment of cancer-associated venous thromboembolism (VTE) is challenging due to thehigh risk of adverse events. While home treatment is quite agreeable to cancer patients, studies evaluating thesafety of VTE home treatment in this setting are largely unavailable.Methods: This was an observational study in patients with cancer-associated VTE. The main outcomes were theproportion of patients treated at home (hospital discharge < 24 h after diagnosis) and the 3-month incidence ofVTE-related adverse events (major bleeding, recurrent VTE and/or suspected VTE-related mortality) in patientsmanaged in hospital versus at home.Results: A total of 183 outpatients were diagnosed with cancer-associated VTE: 69 had deep vein thrombosis(DVT) and 114 had pulmonary embolism (PE ± DVT). Of those, 120 (66%) were treated at home; this was 83%for patients with DVT and 55% for patients with PE ( ± DVT). The 3-month incidence of any VTE-related adverseevent was 13% in those treated at home versus 19% in the hospitalized patients (HR 0.48; 95%CI 0.22–1.1),independent of initial presentation as PE or DVT. All-cause 3-month mortality occurred in 33 patients treated asinpatient (54%) compared to 29 patients treated at home (24%; crude HR 3.1 95%CI 1.9–5.0).Conclusions: Two-third of patients with cancer-associated VTE - including PE - were selected to start antic-oagulant treatment at home. Cancer-associated VTE is associated with high rates of VTE-related adverse eventsindependent of initial in hospital or home treatment. However, home treatment may be a good option forselected patients with cancer-associated DVT or PE. Show less
Verschoor, A.J.; Bovee, J.V.M.G.; Mastboom, M.J.L.; Dijkstra, P.D.S.; Sande, M.A.J. van de; Gelderblom, H. 2018
Many surface waters in The Netherlands do not comply with environmental quality standards for metals. This doesn't mean that the aquatic ecosystem is actually affected. Toxic effects of metals on... Show moreMany surface waters in The Netherlands do not comply with environmental quality standards for metals. This doesn't mean that the aquatic ecosystem is actually affected. Toxic effects of metals on aquatic life (for example fish, crustaceans and algae) are often higher in test with "standard" water, than in natural surface water. This implies that environmental quality standards, which are derived from tests with standard water, may be stricter than necessary to protect aquatic life. As a result, unnecessary and ineffective measures aiming to reduce emissions may be taken Show less
