| 1. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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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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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:5, s. 807-813
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Tidskriftsartikel (refereegranskat)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. |
- Berglund, Eva Caroline, et al.
(författare)
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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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Ingår i: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media SA. - 2296-858X. ; 9, s. 1-9
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Berglund, Åke, et al.
(författare)
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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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Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 53:9, s. 1212-1220
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Tidskriftsartikel (refereegranskat)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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| 4. |
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| 5. |
- Bergström, Ulf, et al.
(författare)
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Pulmonary dysfunction, smoking, socioeconomic status and the risk of developing rheumatoid arthritis.
- 2011
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 50, s. 2005-2013
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Environmental risk factors are of potential interest for both prevention and treatment of RA. The purpose of this study was to examine the effect of pulmonary function, smoking and socio-economic status on the future risk of RA. Methods. Between 1974 and 1992, 22 444 men and 10 902 women were included in the Malmö Preventive Medicine Program (MPMP). Pulmonary function was assessed by a standard screening spirometry. Chronic obstructive pulmonary disease (COPD) and restrictive pulmonary dysfunction were defined based on pulmonary function tests. Individuals who developed RA were identified by linking the MPMP database to national and local RA registers. The patients were classified according to the 1987 ACR criteria for RA. Four matched controls for every case were selected. Results. We identified 290 cases of incident RA (151 men/139 women; mean age at diagnosis 60 years). The median time from inclusion to diagnosis was 12 years. Forced vital capacity and forced expiratory volume within 1 s values were similar in cases and controls, overall and also in separate analysis of those screened ≤8 years before diagnosis. There was no association between COPD or restrictive pulmonary dysfunction and subsequent development of RA. Current smoking was a strong predictor for RA [odds ratio (OR) 1.79; 95% CI 1.32, 2.42]. Blue-collar workers had an increased risk of RA (OR 1.54; 95% CI 1.12, 2.10), independent of smoking. Conclusion. Pulmonary dysfunction did not predict RA, but smoking and low socio-economic status were independent risk factors for RA. Other effects of smoking may be important for RA susceptibility
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| 6. |
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| 7. |
- Boström, Marja L., et al.
(författare)
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A specific, highly enriching and "green" method for hollow fiber liquid phase microextraction of ionizable pharmaceuticals from fish tissue
- 2014
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Ingår i: Analytical Methods. - : Royal Society of Chemistry (RSC). - 1759-9660. ; 6:15, s. 6031-6037
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Tidskriftsartikel (refereegranskat)abstract
- Ionizable pharmaceuticals are a class of emerging contaminants that pose a challenge to analytical chemistry due to their low environmental concentrations. To measure such low concentrations in organism tissue, e.g. fish muscle, specific extraction techniques minimizing co-extraction and interference alongside providing high enrichment of the compounds are needed. In this study we present a technique using hollow fiber liquid phase microextraction which is selective and highly enriching due to a pH gradient across a selective membrane, trapping ions in the extract. Microextraction minimizes the use of organic solvents, thereby making the technique "green". We used high volume pharmaceuticals for method development, specifically, the weak acids ketoprofen, naproxen, diclofenac and ibuprofen, and the weak bases fluoxetine and sertraline. Lyophilized tissue extraction gave higher enrichment than fresh tissue extraction and concentration enrichment factors ranged from 1900 to 3000 times. Method detection limits with the analysis instruments used in this study were for ketoprofen, 0.23 ng g(-1) fish tissue; naproxen, 0.32 ng g(-1) fish tissue; diclofenac, 0.12 ng g(-1) fish tissue; ibuprofen, 0.34 ng g-1 fish tissue; fluoxetine, 13 ng g-1. fish tissue and sertraline, 23 ng g(-1) fish tissue. All analytes were successfully detected in tissue from fish exposed live via spiked water. The resulting extraction parameters shown in this study suggest the developed technique to be a useful work up method for extensive environmental data collection as well as for toxicokinetic studies.
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| 8. |
- Boström, Marja L., et al.
(författare)
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Bioaccumulation and Trophodynamics of the Antidepressants Sertraline and Fluoxetine in Laboratory-Constructed, 3-Level Aquatic Food Chains
- 2017
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Ingår i: Environmental Toxicology and Chemistry. - : John Wiley & Sons. - 0730-7268 .- 1552-8618. ; 36:4, s. 1029-1037
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Tidskriftsartikel (refereegranskat)abstract
- Although reports of pharmaceutical bioconcentration in aquatic organisms are increasing, less is known about trophic transfer in aquatic food webs. The bioaccumulation and trophodynamics of sertraline and fluoxetine, 2 selective serotonin reuptake inhibitors (SSRIs) frequently detected in aquatic environments, were tested by exposing constructed aquatic food chains to SSRIs under controlled laboratory conditions. Both of these ionizable, weak base pharmaceuticals showed lower bioaccumulation factors (BAFs) with increasing trophic level (i.e., no biomagnifications) in 2 3-level food chains (Acer platanoides, fed to Asellus aquaticus, in turn fed to Notonecta glauca or Pungitius pungitius). Mean sertraline BAFs in A. platanoides, A. aquaticus, N. glauca, and P. pungitus were 2200L/kg, 360L/kg, 26L/kg, and 49L/kg, respectively, and mean fluoxetine BAFs 1300L/kg, 110L/kg, 11L/kg, and 41L/kg, respectively. The weak influence of diet was further demonstrated by measured BAFs being equal to or lower than measured bioconcentration factors (BCFs). Organism lipid content was not positively correlated with BAFs, suggesting that other processes are driving interspecific differences in SSRI bioaccumulation. The empirically derived parameter values were introduced into a proposed bioaccumulation model, and a poor correlation was found between modeled and empirical BAFs (predicted r(2)=-0.63). In conclusion, the apparent lack of biomagnification of these ionizable pharmaceuticals suggests that environmental concern should not necessarily focus only on higher trophic levels, but also on species showing high BCFs at any trophic level.
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| 9. |
- Erlandsson, Johan, et al.
(författare)
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Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial
- 2017
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Ingår i: The Lancet Oncology. - : ELSEVIER SCIENCE INC. - 1470-2045 .- 1474-5488. ; 18:3, s. 336-346
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Tidskriftsartikel (refereegranskat)abstract
- Background Radiotherapy reduces the risk of local recurrence in rectal cancer. However, the optimal radiotherapy fractionation and interval between radiotherapy and surgery is still under debate. We aimed to study recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery. Methods In this multicentre, randomised, non-blinded, phase 3, non-inferiority trial (Stockholm III), all patients with a biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and planned for an abdominal resection from 18 Swedish hospitals were eligible. Participants were randomly assigned with permuted blocks, stratified by participating centre, to receive either 5 x 5 Gy radiation dose with surgery within 1 week (short-course radiotherapy) or after 4-8 weeks (short-course radiotherapy with delay) or 25 x 2 Gy radiation dose with surgery after 4-8 weeks (long-course radiotherapy with delay). After a protocol amendment, randomisation could include all three treatments or just the two short-course radiotherapy treatments, per hospital preference. The primary endpoint was time to local recurrence calculated from the date of randomisation to the date of local recurrence. Comparisons between treatment groups were deemed non-inferior if the upper limit of a double-sided 90% CI for the hazard ratio (HR) did not exceed 1.7. Patients were analysed according to intention to treat for all endpoints. This study is registered with ClinicalTrials.gov, number NCT00904813. Findings Between Oct 5, 1998, and Jan 31, 2013, 840 patients were recruited and randomised; 385 patients in the three-arm randomisation, of whom 129 patients were randomly assigned to short-course radiotherapy, 128 to short-course radiotherapy with delay, and 128 to long-course radiotherapy with delay, and 455 patients in the two-arm randomisation, of whom 228 were randomly assigned to short-course radiotherapy and 227 to short-course radiotherapy with delay. In patients with any local recurrence, median time from date of randomisation to local recurrence in the pooled short-course radiotherapy comparison was 33.4 months (range 18.2-62.2) in the short-course radiotherapy group and 19.3 months (8.5-39.5) in the short-course radiotherapy with delay group. Median time to local recurrence in the long-course radiotherapy with delay group was 33.3 months (range 17.8-114.3). Cumulative incidence of local recurrence in the whole trial was eight of 357 patients who received short-course radiotherapy, ten of 355 who received short-course radiotherapy with delay, and seven of 128 who received long-course radiotherapy (HR vs short-course radiotherapy: short-course radiotherapy with delay 1.44 [95% CI 0.41-5.11]; long-course radiotherapy with delay 2.24 [0.71-7.10]; p=0.48; both deemed non-inferior). Acute radiation-induced toxicity was recorded in one patient (amp;lt;1%) of 357 after short-course radiotherapy, 23 (7%) of 355 after short-course radiotherapy with delay, and six (5%) of 128 patients after long-course radiotherapy with delay. Frequency of postoperative complications was similar between all arms when the three-arm randomisation was analysed (65 [50%] of 129 patients in the short-course radiotherapy group; 48 [38%] of 128 patients in the short-course radiotherapy with delay group; 50 [39%] of 128 patients in the long-course radiotherapy with delay group; odds ratio [OR] vs short-course radiotherapy: short-course radiotherapy with delay 0.59 [95% CI 0.36-0.97], long-course radiotherapy with delay 0.63 [0.38-1.04], p=0.075). However, in a pooled analysis of the two short-course radiotherapy regimens, the risk of postoperative complications was significantly lower after short-course radiotherapy with delay than after short-course radiotherapy (144 [53%] of 355 vs 188 [41%] of 357; OR 0.61 [95% CI 0.45-0.83] p=0.001). Interpretation Delaying surgery after short-course radiotherapy gives similar oncological results compared with short-course radiotherapy with immediate surgery. Long-course radiotherapy with delay is similar to both short-course radiotherapy regimens, but prolongs the treatment time substantially. Although radiation-induced toxicity was seen after short-course radiotherapy with delay, postoperative complications were significantly reduced compared with short-course radiotherapy. Based on these findings, we suggest that short-course radiotherapy with delay to surgery is a useful alternative to conventional short-course radiotherapy with immediate surgery.
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