| 1. |
- Gunnlaugsson, Adalsteinn, et al.
(author)
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Multicentre phase II trial of capecitabine and oxaliplatin in combination with radiotherapy for unresectable colorectal cancer : The CORGI-L study
- 2009
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:5, s. 807-813
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Journal article (peer-reviewed)abstract
- AIMS: This study assessed radiotherapy combined with capecitabine and oxaliplatin in patients with primary, inextirpable colorectal adenocarcinoma. PATIENTS AND METHODS: Forty-nine patients entered the trial. Two cycles of XELOX (capecitabine 1000mg/m(2) bid d1-14+oxaliplatin 130mg/m(2) d1, q3w) were followed by radiotherapy (50.4Gy), combined with capecitabine 825mg/m(2) bid every radiotherapy day and oxaliplatin 60mg/m(2) once weekly. The primary end-point was objective response. RESULTS: Forty-seven patients were evaluable. Twenty-nine (62% [95% CI: 46-75%]) achieved complete or partial response. Thirty-eight (81%) went through surgery of whom 37 (97%) had an R0 resection and five (13%) had a pathological complete response. Seventy-eight percent were alive and estimated local progression rate was 11% at 2 years. The most common grade 3+ toxicity during chemoradiotherapy was diarrhoea (24%). CONCLUSIONS: XELOX-RT was feasible and showed promising efficacy when treating patients with primary inextirpable colorectal cancer, establishing high local control rate.
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| 2. |
- Nilsson, Peter, et al.
(author)
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The enigma of increased non-cancer mortality after weight loss in healthy men who are overweight or obese.
- 2002
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In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 252:1, s. 70-78
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Journal article (peer-reviewed)abstract
- Objective. To study effects on non-cancer mortality of observational weight loss in middle-aged men stratified for body mass index (BMI), taking a wide range of possible confounders into account. Design. Prospective, population based study. Setting. Male population of Malmö, Sweden. Participants. In all 5722 men were screened twice with a mean time interval of 6 years in Malmö, southern Sweden. They were classified according to BMI category at baseline (<21, 22-25, overweight: 26-30, and obesity: 30+ kg m-2) and weight change category until second screening (weight stable men defined as having a baseline BMI ± 0.1 kg m-2 year-1 at follow-up re-screening). Main outcome measures. Non-cancer mortality calculated from national registers during 16 years of follow-up after the second screening. Data from the first year of follow-up were excluded to avoid bias by mortality caused by subclinical disease at re-screening. Results. The relative risk (RR; 95% CI) for non-cancer mortality during follow-up was higher in men with decreasing BMI in all subgroups: RR 2.64 (1.46-4.71, baseline BMI <21 kg m-2), 1.39 (0.98-1.95, baseline BMI 22-25 kg m-2), and 1.71 (1.18-2.47, baseline BMI 26+ kg m-2), using BMI-stable men as reference group. Correspondingly, the non-cancer mortality was also higher in men with increasing BMI, but only in the obese group (baseline BMI 26+ kg m-2) with RR 1.86 (1.31-2.65). In a subanalysis, nonsmoking obese (30+ kg m-2) men with decreased BMI had an increased non-cancer mortality compared with BMI-stable obese men (Fischer's test: P=0.001). The mortality risk for nonsmoking overweight men who increased their BMI compared with BMI-stable men was also significant (P=0.006), but not in corresponding obese men (P=0.094). Conclusions. Weight loss in self-reported healthy but overweight middle-aged men, without serious disease, is associated with an increased non-cancer mortality, which seems even more pronounced in obese, nonsmoking men, as compared with corresponding but weight-stable men. The explanation for these observational findings is still enigmatic but could hypothetically be because of premature ageing effects causing so-called weight loss of involution.
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| 3. |
- Berglund, Eva Caroline, et al.
(author)
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A Study Protocol for Validation and Implementation of Whole-Genome and -Transcriptome Sequencing as a Comprehensive Precision Diagnostic Test in Acute Leukemias
- 2022
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In: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media SA. - 2296-858X. ; 9, s. 1-9
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Journal article (peer-reviewed)abstract
- Background: Whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS), with the ability to provide comprehensive genomic information, have become the focal point of research interest as novel techniques that can support precision diagnostics in routine clinical care of patients with various cancer types, including hematological malignancies. This national multi-center study, led by Genomic Medicine Sweden, aims to evaluate whether combined application of WGS and WTS (WGTS) is technically feasible and can be implemented as an efficient diagnostic tool in patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In addition to clinical impact assessment, a health-economic evaluation of such strategy will be performed. Methods and Analysis: The study comprises four phases (i.e., retrospective, prospective, real-time validation, and follow-up) including approximately 700 adult and pediatric Swedish AML and ALL patients. Results of WGS for tumor (90×) and normal/germline (30×) samples as well as WTS for tumors only will be compared to current standard of care diagnostics. Primary study endpoints are diagnostic efficiency and improved diagnostic yield. Secondary endpoints are technical and clinical feasibility for routine implementation, clinical utility, and health-economic impact. Discussion: Data from this national multi-center study will be used to evaluate clinical performance of the integrated WGTS diagnostic workflow compared with standard of care. The study will also elucidate clinical and health-economic impacts of a combined WGTS strategy when implemented in routine clinical care. Clinical Trial Registration: [https://doi.org/10.1186/ISRCTN66987142], identifier [ISRCTN66987142].
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| 4. |
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| 5. |
- Norinder, A, et al.
(author)
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Costs for screening, intervention and hospital treatment generated by the Malmö Preventive Project: a large-scale community screening programme.
- 2002
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In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 251:1, s. 44-52
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The purpose of this study was to estimate retrospectively the costs of health care resources used in the Malmö Preventive Project, Sweden and estimate the costs of in-patient care that were avoided because of early intervention. SETTING AND SUBJECTS: A large-scale community intervention programme was conducted from 1974 to 1992 in Malmö, Sweden with the aim of reducing morbidity and mortality of cardiovascular diseases (CVD), alcohol related illnesses, and breast cancer. Between 1974 and 1992, 33 336 male and female subjects were screened for hypertension, hyperlipidaemia, type-2 diabetes and alcohol abuse. Intervention programmes that included life-style modifications, follow-up visits with physicians and nurses and drug therapy were offered to about 25% of screened subjects. METHODS: Recruitment costs were generated through out the screening period. Intervention costs were estimated for 5 years after screening. Excess in-patient care costs were estimated by subtracting hospital consumption for an unscreened, matched cohort from that of the screened cohort over follow-up periods of 13-19 years. Intervention and excess in-patient care costs were estimated until 1996. RESULTS: The net expenditures for recruitment and intervention was SEK253 million and saved costs for in-patient care of SEK143 millions (1998 prices). Considering the opportunity cost of the resources used in the study, the net cost rises to about SEK200 millions. CONCLUSIONS: The results suggest that only part of the intervention costs were offset by reduction in future morbidity health care costs. This is in line with results from prospective analyses of other primary prevention programmes.
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| 6. |
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| 7. |
- Johnsson, A., et al.
(author)
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A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer : the Nordic ACT Trial
- 2013
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 24:9, s. 2335-2341
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Journal article (peer-reviewed)abstract
- Background: The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC). Patients and methods: Patients with untreated mCRC received doublet chemotherapy + bevacizumab during 18 weeks and those without tumor progression were eligible for randomization to bevacizumab + erlotinib (arm A) or bevacizumab alone (arm B), until progression or unacceptable toxic effect. Results: Of the 249 patients enrolled, 80 started maintenance treatment in arm A and 79 in arm B. The rate of any grade 3/4 toxic effect was 53% in arm A and 13% in arm B. Median PFS was 5.7 months in arm A and 4.2 months in arm B (HR = 0.79; 95% confidence interval 0.55-1.12; P = 0.19). Overall survival (OS) from start of induction chemotherapy was 26.7 months in the randomized population, with no difference between the two arms. Conclusions: The addition of erlotinib to bevacizumab as maintenance treatment after first-line chemotherapy in mCRC did not improve PFS significantly. On-going clinical and translational studies focus on identifying subgroups of patients that may benefit from erlotinib in the maintenance setting.
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| 8. |
- Hagman, H., et al.
(author)
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A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer : the Nordic ACT2 trial
- 2016
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:1, s. 140-147
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Journal article (peer-reviewed)abstract
- Maintenance treatment (mt) with bevacizumab (bev) +/- erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies with bev +/- erlo and low-dose capecitabine (cap). Included patients had mCRC scheduled for first-line therapy, Eastern Cooperative Oncology Group (ECOG) 0-1 and no major comorbidities. Treatment with XELOX/FOLFOX or XELIRI/FOLFIRI + bev was given for 18 weeks. After induction, patients without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev +/- erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression-free survival (PFS) rate (PFSr) at 3 months after start of mt. A pooled analysis of KRAS wt patients from the previous ACT study was performed. We included 233 patients. Median age was 64 years, 62% male, 68% ECOG 0, 52% with primary tumor in situ. A total of 138 patients started mt after randomization. PFSr was 64.7% versus 63.6% in wt-B versus wt-BE, P = 1.000; and 75% versus 66.7% in mut-B versus mut-C, P = 0.579, with no significant difference in median PFS and overall survival (OS). In the pooled cohort, median PFS was 3.7 months in wt-B (N = 64) and 5.7 months in wt-BE (N = 62) (hazard ratios 1.03, 95% confidence interval 0.70-1.50, P = 0.867). The frequency of any grade 3/4 toxicities during mt was: 28%/58%/18%/15% (wt-B/wt-BE/mut-B/mut-C). Addition of erlo to bev as mt in KRAS wt mCRC did not significantly improve PFS or OS, but it did increase toxicity. KRAS status does not seem to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results. NCT01229813.
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| 9. |
- Berglund, Åke, et al.
(author)
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First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies
- 2015
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In: Investigational new drugs. - : Springer Science and Business Media LLC. - 0167-6997 .- 1573-0646. ; 33:6, s. 1232-1241
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Journal article (peer-reviewed)abstract
- Purpose Melflufen (melphalan flufenamide, previously designated J1) is an optimized and targeted derivative of melphalan, hydrolyzed by aminopeptidases overexpressed in tumor cells resulting in selective release and trapping of melphalan, and enhanced activity in preclinical models. Methods This was a prospective, single-armed, open-label, first-in-human, dose-finding phase I/IIa study in 45 adult patients with advanced and progressive solid tumors without standard treatment options. Most common tumor types were ovarian carcinoma (n = 20) and non-small-cell lung cancer (NSCLC, n = 11). Results In the dose-escalating phase I part of the study, seven patients were treated with increasing fixed doses of melflufen (25-130 mg) Q3W. In the subsequent phase IIa part, 38 patients received in total 115 cycles of therapy at doses of 30-75 mg. No dose-limiting toxicities (DLTs) were observed at 25 and 50 mg; at higher doses DLTs were reversible neutropenias and thrombocytopenias, particularly evident in heavily pretreated patients, and the recommended phase II dose (RPTD) was set to 50 mg. Response Evaluation Criteria In Solid Tumors (RECIST) evaluation after 3 cycles of therapy (27 patients) showed partial response in one (ovarian cancer), and stable disease in 18 patients. One NSCLC patient received nine cycles of melflufen and progressed after 7 months of therapy. Conclusions In conclusion, melflufen can safely be given to cancer patients, and the toxicity profile was as expected for alkylating agents; RPTD is 50 mg Q3W. Reversible and manageable bone marrow suppression was identified as a DLT. Clinical activity is suggested in ovarian cancer, but modest activity in treatment of refractory NSCLC.
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| 10. |
- Berglund, Åke, et al.
(author)
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The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab
- 2014
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In: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 53:9, s. 1212-1220
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Journal article (peer-reviewed)abstract
- It is debated whether cancer patients treated with chemotherapy can mount an adequate response to vaccination.Material and methods: Ninety-six adult outpatients with cancer, who were undergoing chemotherapy and/or monoclonal antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments, were studied. Two doses of the pandemic infl uenza A(H1N1)/09 AS03-adjuvanted split virion vaccine, one dose of the seasonal infl uenza vaccine and one dose of the 23-valent pneumococcal polysaccharide vaccine were given. Serum haemagglutination inhibition (HI) assays were used to determine antibody titres against the infl uenza strains. For the pneumococcal vaccine 14 different serotypespecifi c anti-capsular antibodies were measured by bead assay xMAP ® .Results: Patients treated with rituximab did not respond to vaccination. For patients without rituximab treatment 4% had putatively protective antibodies before vaccination (HI 40) to the pandemic-like strain A/California7/2009HINI. After the fi rst and second dose of vaccine, seroprotection rates (SPR) were 62% and 87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal fl u vaccination SPR against infl uenza A/Brisbane/59/2007H1N1 and A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were 70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine protective antibodies were found to 40% of the 14 strains before and to 68% after vaccination. The mean response to pneumococcal vaccination was to 44% of the 14 serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the patients. No serious adverse events were reported.Conclusion: A substantial number of adult cancer patients with ongoing chemotherapy treatment could mount an adequate serological response to infl uenza and pneumococcal vaccination without severe adverse events. Thus, vaccination should be recommended. Adjuvanted vaccines may improve the vaccine response among this patient group. Patients recently treated with rituximab do not respond to vaccination.
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