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- Osterlund, P., et al.
(författare)
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Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study
- 2022
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Ingår i: ESMO Open. - : Elsevier. - 2059-7029. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce.Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity.Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/ infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11).Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.
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- Galleberg, R. B., et al.
(författare)
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Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas
- 2017
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 43:9, s. 1682-1689
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce. The aim of this study was to evaluate the results of curatively intended resection/radiofrequency ablation (RFA) of liver metastases in patients with metastatic GEP-NEC. Methods: 32 patients with a diagnosis of high-grade gastroenteropancreatic neuroendocrine neoplasm (Ki-67 > 20%) and with intended curative resection/RFA of liver metastases, were identified among 840 patients from two Nordic GEP-NEC registries. Tumor morphology (well vs poor differentiation) was reassessed. Overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan Meier analyses for the entire cohort and for subgroups. Results: Median OS after resection/RFA of liver metastases was 35.9 months (95% -CI: 20.6-51.3) with a five-year OS of 43%. The median PFS was 8.4 months (95% -CI: 3.9-13). Four patients (13%) were disease -free after 5 years. Two patients had well -differentiated morphology (NET G3) and 20 patients (63%) had Ki-67 >= 55%. A Ki-67 < 55% and receiving adjuvant chemotherapy were statistically significant factors of improved OS after liver resection/RFA. Conclusion: This study shows a long median and long term survival after liver surgery/RFA for these selected metastatic GEP-NEC patients, particularly for the group with a Ki-67 in the relatively lower G3 range. Our findings indicate a possible role for surgical treatment of liver metastases in the management of this patient population.
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- Orell, HK, et al.
(författare)
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GLIM in diagnosing malnutrition and predicting outcome in ambulatory patients with head and neck cancer
- 2022
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Ingår i: Frontiers in nutrition. - : Frontiers Media SA. - 2296-861X. ; 9, s. 1030619-
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to determine the prevalence of malnutrition in a head and neck cancer (HNC) population according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and to assess its relation to survival. The secondary aim was to compare GLIM criteria to Patient–Generated Subjective Global Assessment (PG–SGA) and Nutritional Risk Screening 2002 (NRS 2002) methods.MethodsThe assessment was performed in a series of 65 curative patients with newly diagnosed HNC in a nutrition intervention study. Malnutrition was defined as PG-SGA classes BC and nutritional risk as NRS 2002 score ≥3 and was retrospectively diagnosed with GLIM criteria in prospectively collected data at diagnosis. Sensitivity, specificity, and kappa (κ) were analyzed. Predictive accuracy was assessed by calculating the area under curve (AUC) b y receiver operating characteristic (ROC) analysis. Kaplan–Meier and Cox regression analyses were used to evaluate association between malnutrition and overall survival (OS), and disease-free survival (DFS).ResultsGLIM-defined malnutrition was present in 37% (24/65) of patients. The GLIM showed 77% sensitivity and 84% specificity with agreement of κ = 0.60 and accuracy of AUC = 0.80 (p < 0.001) with PG-SGA and slightly higher sensitivity (83%) with NRS 2002 (κ = 0.58). Patients with GLIM-defined malnutrition had shorter OS (56 vs. 72 months, HR 2.26, 95% CI 1.07–4.77, p = 0.034) and DFS (37 vs. 66 months, HR 2.01, 95% CI 0.99–4.09, p = 0.054), than well-nourished patients. The adjusted HR was 2.53 (95% CI 1.14–5.47, p = 0.023) for OS and 2.10 (95% CI 0.98–4.48, p = 0.056) for DFS in patients with GLIM-defined malnutrition.ConclusionA substantial proportion of HNC patients were diagnosed with malnutrition according to the GLIM criteria and this showed a moderate agreement with NRS 2002- and PG–SGA-defined malnutrition. Even though the GLIM criteria had strong association with OS, its diagnostic value was poor. Therefore, the GLIM criteria seem potential for malnutrition diagnostics and outcome prediction in the HNC patient population. Furthermore, NRS 2002 score ≥3 indicates high nutritional risk in this patient group.
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- Carlsson, Karin, et al.
(författare)
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Site-directed fluorescence probing to dissect the calcium-dependent association between soluble tissue factor and factor VIIa domains
- 2003
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Ingår i: Biochimica et Biophysica Acta - Proteins and Proteomics. - 1570-9639 .- 1878-1454. ; 1648:1-2, s. 12-16
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Tidskriftsartikel (refereegranskat)abstract
- We have used the site-directed labeling approach to study the Ca 2+-dependent docking of factor VIIa (FVIIa) to soluble tissue factor (sTF). Nine Ca2+ binding sites are located in FVIIa and even though their contribution to the overall binding between TF and FVIIa has been thoroughly studied, their importance for local protein-protein interactions within the complex has not been determined. Specifically we have monitored the association of the ?-carboxyglutamic acid (Gla), the first EGF-like (EGF1), and the protease domains (PD) of FVIIa to sTF. Our results revealed that complex formation between sTF and FVIIa during Ca2+ titration is initiated upon Ca2+ binding to EGF1, the domain containing the site of highest Ca2+ affinity. Besides we showed that a Ca 2+-loaded Gla domain is required for an optimal association of all domains of FVIIa to sTF. Ca2+ binding to the PD seems to be of some importance for the docking of this domain to sTF. © 2003 Elsevier Science B.V. All rights reserved.
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- Horgan, D, et al.
(författare)
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How Can the EU Beating Cancer Plan Help in Tackling Lung Cancer, Colorectal Cancer, Breast Cancer and Melanoma?
- 2022
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Ingår i: Healthcare (Basel, Switzerland). - : MDPI AG. - 2227-9032. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is the second leading cause of mortality in EU countries, and the needs to tackle cancer are obvious. New scientific understanding, techniques and methodologies are opening up horizons for significant improvements in diagnosis and care. However, take-up is uneven, research needs and potential outstrip currently available resources, manifestly beneficial practices—such as population-level screening for lung cancer—are still not generalised, and the quality of life of patients and survivors is only beginning to be given attention it merits. This paper, mainly based on a series of multistakeholder expert workshops organised by the European Alliance for Personalised Medicine (EAPM), looks at some of those specifics in the interest of planning a way forward. Part of this exercise also involves taking account of the specific nature of Europe and its constituent countries, where the complexities of planning a way forward are redoubled by the wide variations in national and regional approaches to cancer, local epidemiology and the wide disparities in health systems. Despite all the differences between cancers and national and regional resources and approaches to cancer care, there is a common objective in pursuing broader and more equal access to the best available care for all European citizens.
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