| 1. |
- Tran, K. B., et al.
(författare)
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The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet. - 0140-6736. ; 400:10352, s. 563-591
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Tidskriftsartikel (refereegranskat)abstract
- Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 2. |
- Cousin, E., et al.
(författare)
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Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 10:3, s. 177-192
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990-2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73.7% (68.3 to 77.4) were classified as due to type 1 diabetes. The age-standardised death rate was 0.50 (0.44 to 0.58) per 100 000 population, and 15 900 (97.5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0.13 (0.12 to 0.14) per 100 000 population in the high SDI quintile, 0.60 (0.51 to 0.70) per 100 000 population in the low-middle SDI quintile, and 0.71 (0.60 to 0.86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r(2)=0.62). From 1990 to 2019, age-standardised death rates decreased globally by 17.0% (-28.4 to -2.9) for all diabetes, and by 21.0% (-33.0 to -5.9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (-13.6% [-28.4 to 3.4]) and for type 1 diabetes (-13.6% [-29.3 to 8.9]). Interpretation Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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| 3. |
- Kristensen, G B, et al.
(författare)
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First-line treatment of ovarian cancer FIGO stages IIb-IV with paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin.
- 2003
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Ingår i: International Journal of Gynecological Cancer. - : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 13:s2, s. 172-177
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to compare the safety and efficacy of carboplatin plus epirubicin and paclitaxel (TEC) to carboplatin and paclitaxel (TC), in the treatment of epithelial ovarian, peritoneal, or tubal carcinoma. Between March 1999 and August 2001, 887 patients were randomized to receive six to nine cycles of paclitaxel (175 mg/m2, 3 h intravenously) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m2 intravenously prior to paclitaxel), on a 3-weekly schedule. The primary endpoint was progression-free survival. Demographic information: Residual disease <1 cm was reported on 41% of patients. At the end of treatment, 65% in the TEC and 55% in the TC arm had achieved a clinical complete response, and 18 and 25% a clinical partial response resulting in an overall response rate of 83% in the TEC and 80% in the TC arm, whereas 7 and 9% had progressive disease, respectively. The three-drug combination produced a markedly higher myelotoxicity, resulting in a higher frequency of febrile neutropenia (12.5% of the TEC and 1.5% of the TC patients) and a higher number of dose reductions and treatment delays. Cycle prolongation above seven days was seen in 7 and 5% of cycles in the TEC and TC arm, respectively. Stomatitis > or = grade 3 was also higher with TEC (4% TEC and 0.5% TC). Reductions in left ventricular ejection fraction of more than 15% after six courses were slightly more common with the TEC regimen (3% versus 1.5%), but the difference was not statistically significant (P = 0.2). In conclusion, treatment with the TEC combination produced a higher rate of complete responses than treatment with the TC combination. Toxicity was manageable. Long-term survival data are awaited.
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| 4. |
- Mirza, M. R., et al.
(författare)
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Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer
- 2016
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 375:22, s. 2154-2164
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. METHODS In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2: 1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. RESULTS Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P amp;lt; 0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. CONCLUSIONS Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274.)
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| 5. |
- Ray-Coquard, I., et al.
(författare)
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Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:2, s. 439-448
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Tidskriftsartikel (refereegranskat)abstract
- AGO-OVAR 12 investigated the effect of adding the oral triple angiokinase inhibitor nintedanib to standard front-line chemotherapy for advanced ovarian cancer. At the primary analysis, nintedanib demonstrated significantly improved progression-free survival (PFS; primary endpoint) compared with placebo. We report final results, including overall survival (OS). Patients with primary debulked International Federation of Gynaecology and Obstetrics (FIGO) stage IIB–IV newly diagnosed ovarian cancer were randomised 2:1 to receive carboplatin (area under the curve 5 or 6) plus paclitaxel (175 mg/m2) on day 1 every 3 weeks for six cycles combined with either nintedanib 200 mg or placebo twice daily on days 2–21 every 3 weeks for up to 120 weeks. Between December 2009 and July 2011, 1,366 patients were randomised (911 to nintedanib, 455 to placebo). Disease was considered as high risk (FIGO stage III with amp;gt;1 cm residuum, or any stage IV) in 39%. At the final analysis, 605 patients (44%) had died. There was no difference in OS (hazard ratio 0.99, 95% confidence interval [CI] 0.83–1.17, p = 0.86; median 62.0 months with nintedanib vs. 62.8 months with placebo). Subgroup analyses according to stratification factors, clinical characteristics and risk status showed no OS difference between treatments. The previously reported PFS improvement seen with nintedanib did not translate into an OS benefit in the nonhigh-risk subgroup. Updated PFS results were consistent with the primary analysis (hazard ratio 0.86, 95% CI 0.75–0.98; p = 0.029) favouring nintedanib. The safety profile was consistent with previous reports. © 2019 UICC
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| 6. |
- Sharma, R., et al.
(författare)
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Global, regional, and national burden of colorectal cancer and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:7, s. 627-647
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Tidskriftsartikel (refereegranskat)abstract
- Background Colorectal cancer is the third leading cause of cancer deaths worldwide. Given the recent increasing trends in colorectal cancer incidence globally, up-to-date information on the colorectal cancer burden could guide screening, early detection, and treatment strategies, and help effectively allocate resources. We examined the temporal patterns of the global, regional, and national burden of colorectal cancer and its risk factors in 204 countries and territories across the past three decades. Methods Estimates of incidence, mortality, and disability-adjusted life years (DALYs) for colorectal cancer were generated as a part of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019 by age, sex, and geographical location for the period 1990-2019. Mortality estimates were produced using the cause of death ensemble model. We also calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. Findings Globally, between 1990 and 2019, colorectal cancer incident cases more than doubled, from 842 098 (95% uncertainty interval [UI] 810 408-868 574) to 2.17 million (2.00-2.34), and deaths increased from 518 126 (493 682-537 877) to 1.09 million (1.02-1.15). The global age-standardised incidence rate increased from 22.2 (95% UI 21.3-23.0) per 100 000 to 26.7 (24.6-28.9) per 100 000, whereas the age-standardised mortality rate decreased from 14.3 (13.5-14.9) per 100 000 to 13.7 (12.6-14.5) per 100 000 and the age-standardised DALY rate decreased from 308.5 (294.7-320.7) per 100 000 to 295.5 (275.2-313.0) per 100 000 from 1990 through 2019. Taiwan (province of China; 62.0 [48.9-80.0] per 100 000), Monaco (60.7 [48.5-73.6] per 100 000), and Andorra (56.6 [42.8-71.9] per 100 000) had the highest age-standardised incidence rates, while Greenland (31.4 [26.0-37.1] per 100 000), Brunei (30.3 [26.6-34.1] per 100 000), and Hungary (28.6 [23.6-34.0] per 100 000) had the highest age-standardised mortality rates. From 1990 through 2019, a substantial rise in incidence rates was observed in younger adults (age <50 years), particularly in high Socio-demographic Index (SDI) countries. Globally, a diet low in milk (15.6%), smoking (13.3%), a diet low in calcium (12.9%), and alcohol use (9.9%) were the main contributors to colorectal cancer DALYs in 2019. Interpretation The increase in incidence rates in people younger than 50 years requires vigilance from researchers, clinicians, and policy makers and a possible reconsideration of screening guidelines. The fast-rising burden in low SDI and middle SDI countries in Asia and Africa calls for colorectal cancer prevention approaches, greater awareness, and cost-effective screening and therapeutic options in these regions. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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| 7. |
- Vergote, I., et al.
(författare)
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European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer
- 2022
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 33:3, s. 276-287
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Forskningsöversikt (refereegranskat)abstract
- Background: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition.Design: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts' consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.Results: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive.Conclusion: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer.
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| 8. |
- Wilking, N., et al.
(författare)
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Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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