المؤلفون: Hamfjord, J., Guren, T. K., Dajani, O., Johansen, J. S., Glimelius, Bengt, Sorbye, H., Pfeiffer, P., Lingjaerde, O. C., Tveit, K. M., Kure, E. H., Pallisgaard, N., Spindler, K-L.G.

المصدر: Annals of Oncology. 30(7):1088-1095

مصطلحات موضوعية: colorectal cancer, circulating cell-free DNA, interleukin 6, RAS, BRAF, prognostic biomarker

الوصف: Background Metastatic colorectal cancer (mCRC) is a heterogeneous disease where prognosis is dependent both on tumor biology and host factors. Total circulating cell-free DNA (cfDNA) has shown to harbor prognostic information in mCRC, although less is known about the biological correlates of cfDNA levels in this patient group. The primary objective was to evaluate the prognostic value of pretreatment cfDNA in patients receiving the first-line oxaliplatin-based chemotherapy for mCRC, by using a predefined upper limit of normal (ULN) from a cohort of presumed healthy individuals. The secondary objective was to model cfDNA levels as a function of predefined tumor and host factors. Patients and methods This was a retrospective post hoc study based on a prospective multicenter phase III trial, the NORDIC-VII study. DNA was purified from 547 plasma samples and cfDNA quantified by a droplet digital PCR assay (B2M, PPIA) with controls for lymphocyte contamination. Main clinical end point was overall survival (OS). Results cfDNA was quantified in 493 patients, 54 were excluded mainly due to lymphocyte contamination. Median cfDNA level was 7673 alleles/ml (1050-1645000) for B2M and 5959 alleles/ml (555-854167) for PPIA. High cfDNA levels were associated with impaired outcome; median OS of 16.6months for levels above ULN and 25.9months for levels below ULN (hazard ratio = 1.83, 95% confidence interval 1.51-2.21, P<0.001). The result was confirmed in multivariate OS analysis adjusting for established clinicopathological characteristics. A linear regression model predicted cfDNA levels from sum of longest tumor diameters by RECIST, the presence of liver metastases and systemic inflammatory response as measured by interleukin 6 (F(6, 357) = 62.7, P<0.001). Conclusion cfDNA holds promise as a minimally invasive and clinically relevant prognostic biomarker in mCRC before initiating first-line oxaliplatin-based chemotherapy and may be a complex entity associated with tumor burden, liver metastases and systemic inflammatory response. Trial registration ClinicalTrials.gov, NCT00145314.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-394653Test
https://doi.org/10.1093/annonc/mdz139Test
https://uu.diva-portal.org/smash/get/diva2:1361326/FULLTEXT01.pdfTest

المؤلفون: Duvetorp, Albert, Ostergaard, M., Skov, L., Seifert, Oliver, Tveit, K. S., Danielsen, K., Iversen, Lars

المصدر: Archives of Dermatological Research. 311(5):351-360

مصطلحات موضوعية: Psoriasis, Psoriatic arthritis, Quality of life, Depression

الوصف: Psoriasis (skin psoriasis, PsO) is a chronic inflammatory condition. In about one-third of cases, the joints are affected (psoriatic arthritis, PsA). Both conditions, especially PsA, profoundly impact patients health-related quality of life (HRQoL). To describe the impact of psoriasis on HRQoL and patients contact with the healthcare system in Sweden, Denmark, and Norway, the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP) asked 22,050 adults randomly selected in Sweden, Denmark and Norway if they had psoriasis. 1264 individuals who reported physician-diagnosed PsO/PsA were invited to the full survey; 1221 responded (74.6% diagnosed with PsO alone; 25.4% with PsA +/- PsO). Respondents with PsA most frequently consulted a rheumatologist; however, 14.3% had never seen a rheumatologist. Respondents with PsO alone most frequently consulted a general practitioner and 10.7% had never seen a dermatologist (although those with severe symptoms visited dermatologists more often). Negative impacts on HRQoL were reported by 38.1% of respondents with PsO [mostly limitations on clothing (22.6%), sleep disorders (16%), and depression/anxiety (16%)] and by 73% of respondents with PsA [mostly limitations on clothing (41.8%), sports/leisure (44.0%), or daily routine (45.1%) and sleeping disorders]. Absence from work/education was more common with PsA +/- PsO (51.9%) than PsO alone (15.1%). In this survey in Sweden, Denmark, and Norway, the impact of psoriasis on the respondents HRQoL was profound and was greater for PsA than for PsO, as was sickness absence. Sleeping disorders and depression were common and should not be overlooked.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-158538Test
https://liu.diva-portal.org/smash/get/diva2:1334924/FULLTEXT01.pdfTest

المؤلفون: Tveit, K. S., Duvetorp, Albert, Ostergaard, M., Skov, L., Danielsen, K., Iversen, L., Seifert, Oliver

المصدر: Journal of the European Academy of Dermatology and Venereology. 33(2):340-354

الوصف: Background There are scarce data in Scandinavia about treatment satisfaction among patients with psoriasis (PsO) and/or psoriatic arthritis (PsA). The number of patients receiving systemic treatment is unknown. Objective To describe patients experience of treatments for PsO/PsA in Sweden, Denmark and Norway, addressing communication with physicians, satisfaction with treatment and concerns regarding treatment options. Methods The NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP) asked 22 050 adults (randomly selected from the YouGov panels in Sweden, Denmark and Norway) whether they had PsO/PsA. A total of 1264 individuals who reported physician-diagnosed PsO/PsA were invited to participate in the full survey; 96.6% responded positively. Results Systemic treatment use was reported by 14.6% (biologic: 8.1%) of respondents with PsO only and by 58.5% (biologic: 31.8%) of respondents with PsA. Biologic treatments were more frequently reported by respondents considering their disease severe (26.8% vs 6.7% non-severe) and those who were members of patient organizations (40.7% vs 6.9% non-members). Discussing systemic treatments with their physician was reported significantly more frequently by respondents with PsA, those perceiving their disease as severe (although 35.2% had never discussed systemic treatment with their physician) and those reporting being a member of a patient organization (P amp;lt; 0.05). Many respondents reported health risk concerns and dissatisfaction with their treatment. Of special interest was that respondents aged 45-75 years reported less experience with biologics (8.1%) than those aged 18-44 years (21.5%). The older respondents also reported more uncertainty regarding long-term health risks related to systemic treatments (most [66.7-72.9%] responded do not know when asked about the risk of systemic options). Conclusion It appears likely that substantial numbers of Scandinavians suffering from severe PsO/PsA are not receiving optimal treatment from a patient perspective, particularly older patients. Also, one-third of respondents with severe symptoms had never discussed systemic treatment with a physician.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-154669Test
https://liu.diva-portal.org/smash/get/diva2:1293181/FULLTEXT01.pdfTest

المؤلفون: Glimelius, B., Sorbye, H., Balteskard, L., Bystrom, P., Pfeiffer, P., Tveit, K., Heikkila, R., Keldsen, N., Albertsson, Maria, Starkhammar, H., Garmo, H., Berglund, A.

المصدر: Annals of Oncology. 19(5):909-914

مصطلحات موضوعية: chemotherapy, irinotecan, 5-fluorouracil, randomized trial, colorectal cancer, Medicin och hälsovetenskap, Klinisk medicin, Cancer och onkologi, Medical and Health Sciences, Clinical Medicine, Cancer and Oncology

الوصف: Background: To compare irinotecan with the Nordic 5- fluorouracil (5- FU) and folinic acid (FA) bolus schedule [ irinotecan 180 mg/m(2) on day 1, 5- FU 500 mg/m(2) and FA 60 mg/m(2) on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [ irinotecan 180 mg/m(2) on day 1, FA 200 mg/m(2), 5- FU bolus 400 mg/m(2) and infused 5- FU 600 mg/m(2) on day 1 and 2 (Lv5FU2- IRI)] due to uncertainties about how to administrate 5- FU with irinotecan. Patients and methods: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2- IRI. Primary end point was progression- free survival (PFS). Results: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did not differ (4% versus 6%, P = 0.3). Grade 3/4 neutropenia (11% versus 5%, P = 0.01) and grade 2 alopecia (18% versus 9%, P = 0.002) were more common in the FLIRI group. The 60- day mortality was 2.4% versus 2.1%. Conclusions: Irinotecan with the bolus Nordic schedule (FLIRI) is a convenient treatment with PFS and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated.

الوصول الحر: https://lup.lub.lu.se/record/1204941Test
http://dx.doi.org/10.1093/annonc/mdm588Test

المؤلفون: Tveit, K., Hermann, M., Waade, R. B., Nilsen, R. M., Wallerstedt, Susanna Maria, 1970, Molden, E.

المصدر: Drugs & Aging. 39(691-701)

مصطلحات موضوعية: Geriatrics, Geriatrik

الوصف: Background According to previous studies, older patients frequently have serum concentrations of antidepressant medication above the recommended reference range. Objective The aim of this study was to investigate whether prescribed doses of antidepressants and the proportion of individuals with serum concentrations above the recommended reference range in older individuals (>= 65 years) have changed over a 10-year period in Norway. Methods Serum concentration measurements and prescribed daily doses of antidepressants in 2007 and 2017 were extracted from a therapeutic drug monitoring (TDM) database at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. The database contains routine follow-up serum concentration measurements of psychotropic drugs for patients from all parts of the country. For citalopram, escitalopram, sertraline, mirtazapine and venlafaxine, the differences between 2007 and 2017 in mean prescribed doses and the proportion of patients with at least one serum concentration above the reference range, according to the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) guidelines, were compared. For the proportion of patients with serum concentrations above the recommended reference range, differences between individuals aged 65-79 and >= 80 years were also examined. Results The analyses of prescribed doses included 806 patients from 2007 and 1932 patients from 2017, with 972 and 2441 TDM samples, respectively. Between 2007 and 2017, modest reductions in prescribed daily doses were observed for citalopram (20 vs. 17 mg/day) and escitalopram (11 vs. 10 mg/day), but the proportion of patients with serum concentrations above the recommended reference range was unchanged for both drugs, i.e. 11.5% vs. 12.4% for citalopram and 3.6% vs. 2.9% for escitalopram. For mirtazapine and venlafaxine, prescribed doses were reduced from 28 to 25 mg/day and 150 to 125 mg/day, respectively. A significant reduction in the proportion of individuals with serum concentrations above the recommended reference range was observed for mirtazapine (27.1% vs. 11.5%) and for individuals aged >= 80 years using venlafaxine (60.0% vs. 30.0%). For sertraline, no differences in prescribed doses or serum concentrations above the recommended reference range were observed. Conclusions Over a 10-year period, prescribed doses of antidepressants have been slightly reduced in older Norwegian patients, but a considerable proportion is still exposed to high serum concentrations of antidepressants.

الوصول الحر: https://gup.ub.gu.se/publication/295505Test

المؤلفون: Kjersem, J B, Thomsen, M, Guren, T, Hamfjord, J, Carlsson, Göran, 1951, Gustavsson, Bengt, 1947, Ikdahl, T, Indrebø, G, Pfeiffer, P, Lingjærde, O, Tveit, K M, Wettergren, Yvonne, 1957, Kure, E H

المصدر: The pharmacogenomics journal. 16(3):272-279

مصطلحات موضوعية: Surgery, Kirurgi

الوصف: The objective of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) with influence on drug transport, biotransformation and repair mechanisms are associated with treatment outcome and toxicity in metastatic colorectal cancer (mCRC). We genotyped blood samples from 519 mCRC patients treated with first-line 5-fluorouracil and oxaliplatin +/- cetuximab for 17 SNPs in 10 genes involved in membrane transport (ABCC1 and ABCC2), drug biotransformation (GSTP1 and AGXT) and DNA repair (ERCC1, ERCC2, XRCC1, XRCC3, XPG and MSH6). The AGXT-rs34116584 and the ERCC2-rs238406 polymorphisms were significantly associated with progression-free survival (P=0.002 and P=0.001, respectively). Associations between 18 toxicity variables and SNPs were identified, although none were significant after Bonferroni correction for multiple comparisons. The study identified SNPs of potential use as markers of clinical outcome in oxaliplatin-treated mCRC patients. If validated in other studies, they could improve the selection of therapy in mCRC.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.54.

الوصول الحر: https://gup.ub.gu.se/publication/222215Test

المؤلفون: Qvortrup, Camilla, Yilmaz, M., Ogreid, D., Berglund, Åke, Balteskard, L., Ploen, J., Fokstuen, T., Starkhammar, H., Sørbye, H., Tveit, K., Pfeiffer, P.

المصدر: Annals of Oncology. 19(6):1154-9

مصطلحات موضوعية: capecitabine, chronotherapy, metastatic colorectal cancer, oxaliplatin, short-time infusion, XELOX, MEDICINE, MEDICIN

الوصف: BACKGROUND: Oxaliplatin in combination with capecitabine prolongs survival in patients with metastatic colorectal cancer (mCRC). Chronomodulation might reduce toxicity and improve efficacy. PATIENTS AND METHODS: A phase II study examining chronomodulated XELOX(30) (XELOX(30chron)): oxaliplatin: 130 mg/m(2) on day 1, as a 30-min infusion between 1 and 3 p.m. Capecitabine: total daily dose of 2000 mg/m(2), 20% of the dose between 7 and 9 a.m. and 80% of the dose between 6 and 8 p.m. in patients with mCRC resistant to irinotecan. Seventy-one patients were enrolled. Response rate was 18%; median progression-free survival 5.1 months and median overall survival (OS) 10.2 months. Platelet count and performance status were significantly correlated to OS in multivariate analyses. Neurotoxicity grade 2 and 3 was seen in 25% and 2% of patients, respectively, other grade 3 toxic effects were as follows: nausea 6%, vomiting 3%, diarrhoea 12% (3% experienced grade 4) and palmoplantart erytem 9%. CONCLUSION: XELOX(30chron) is a convenient second-line regimen with efficacy and safety profile similar to other oxaliplatin schedules. To further investigate chronomodulated XELOX, we have started a Nordic randomised phase II study comparing XELOX(30) and XELOX(30chron) as first-line therapy in patients with mCRC.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-105354Test

المؤلفون: Pfeiffer, P, Sorbye, H, Ehrsson, H, Fokstuen, T, Mortensen, J P, Baltesgard, L, Tveit, K M, Ogreid, D, Starkhammar, H, Wallin, I, Qvortrup, C, Glimelius, B

المصدر: Ann Oncol. 17(2):252-8

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-25381Test
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=16291583&dopt=CitationTest

المؤلفون: Glimelius, B., Dahl, O., Cedermark, B., Jakobsen, A., Bentzen, S. M., Starkhammar, H., Gronberg, H., Hultborn, Ragnar, 1946, Albertsson, M., Pahlman, L., Tveit, K. M.

المصدر: Acta Oncol. 44(8):904-12

مصطلحات موضوعية: Cancer and Oncology, Cancer och onkologi, Adenocarcinoma/drug therapy/surgery, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Chemotherapy, Adjuvant, Colorectal Neoplasms/*drug therapy/surgery, Combined Modality Therapy, Female, Fluorouracil/administration & dosage, Humans, Leucovorin/administration & dosage, Levamisole/administration & dosage, Male, Middle Aged, Neoplasm Staging, Survival Rate

الوصف: Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to+/-levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations.

الوصول الحر: https://gup.ub.gu.se/publication/52337Test

المؤلفون: Myklebust, M P, Li, Z, Tran, T H, Rui, H, Knudsen, E S, Elsaleh, H, Fluge, Ø, Vonen, B, Myrvold, H E, Leh, S, Tveit, K M, Pestell, R G, Dahl, O

المصدر: British Journal of Cancer; 11/6/2012, Vol. 107 Issue 10, p1684-1691, 8p, 2 Color Photographs, 1 Chart, 3 Graphs

مصطلحات موضوعية: COLON cancer treatment, CYCLINS, CANCER chemotherapy, FLUOROURACIL, LEVAMISOLE, IMMUNOHISTOCHEMISTRY, BIOMARKERS

مستخلص: Background:The aim of this study was to investigate the value of the cyclin D1 isoforms D1a and D1b as prognostic factors and their relevance as predictors of response to adjuvant chemotherapy with 5-fluorouracil and levamisole (5-FU/LEV) in colorectal cancer (CRC).Methods:Protein expression of nuclear cyclin D1a and D1b was assessed by immunohistochemistry in 335 CRC patients treated with surgery alone or with adjuvant therapy using 5-FU/LEV. The prognostic and predictive value of these two molecular markers and clinicopathological factors were evaluated statistically in univariate and multivariate survival analyses.Results:Neither cyclin D1a nor D1b showed any prognostic value in CRC or colon cancer patients. However, high cyclin D1a predicted benefit from adjuvant therapy measured in 5-year relapse-free survival (RFS) and CRC-specific survival (CSS) compared to surgery alone in colon cancer (P=0.012 and P=0.038, respectively) and especially in colon cancer stage III patients (P=0.005 and P=0.019, respectively) in univariate analyses. An interaction between treatment group and cyclin D1a could be shown for RFS (P=0.004) and CSS (P=0.025) in multivariate analysis.Conclusion:Our study identifies high cyclin D1a protein expression as a positive predictive factor for the benefit of adjuvant 5-FU/LEV treatment in colon cancer, particularly in stage III colon cancer. [ABSTRACT FROM AUTHOR]

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