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Sökning: WFRF:(Glimelius Bengt) > Pfeiffer Per

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1.
  • Aasebo, Kristine, et al. (författare)
  • CDX2 : A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup
  • 2020
  • Ingår i: Frontiers in Oncology. - : FRONTIERS MEDIA SA. - 2234-943X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Survival of metastatic colorectal cancer (mCRC) patients has improved, but mainly for trial patients. New predictive and prognostic biomarkers validated in the general mCRC population are needed. Caudal-type homeobox 2 (CDX2) is an intestine-specific transcription factor with potential prognostic and predictive effect, but the importance in mCRC has not been fully investigated. Methods: Immunohistochemistry analysis of CDX2 was performed in a Scandinavian population-based cohort of mCRC (n = 796). Frequency, clinical and tumor characteristics, response rate, progression-free survival, and overall survival (OS) were estimated. Results: Loss of CDX2 expression was found in 87 (19%) of 452 stained cases, in 53% if BRAF mutated (BRAFmut) and in 9% if KRAS mutated (KRASmut). CDX2 loss was associated with microsatellite instability, BRAFmut, and poor differentiation and inversely associated with KRASmut. Patients with CDX2 loss received less first-line (53 vs. 64%, p = 0.050) and second-line (23 vs. 39%, p = 0.006) chemotherapy and secondary surgery (1 vs. 9%, p = 0.019). Median progression-free survival and OS for patients given first-line combination chemotherapy was 4 and 10 months if CDX2 loss vs. 9 and 24 months if CDX2 expressed (p = 0.001, p < 0.001). Immediate progression on first-line combination chemotherapy was seen in 35% of patients with CDX2 loss vs. 10% if CDX2 expressed (p = 0.003). Median OS in patients with BRAFmut or KRASmut and CDX2 expressed in tumor (both 21 months) was comparable to wild-type patients (27 months). However, if CDX2 loss, median OS was only 8 and 11 months in BRAFmut and KRASmut cases, respectively, and 10 months in double wild-type patients. In multivariate analysis, CDX2 loss (hazard ratio: 1.50, p = 0.027) and BRAFmut (hazard ratio: 1.62, p = 0.012) were independent poor prognostic markers for OS. Conclusion: In a population-based cohort of mCRC patients, CDX2 loss is an independent poor prognostic marker. Expression of CDX2 defines a new subgroup of BRAFmut cases with a much better prognosis. Loss of CDX2 defines a small group of KRASmut cases with a worse prognosis. Patients with CDX2 loss receive less palliative chemotherapy with less benefit and rarely reach secondary surgery.
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2.
  • Aasebø, Kristine, et al. (författare)
  • Prognostic role of tumour-infiltrating lymphocytes and macrophages in relation to MSI, CDX2 and BRAF status : a population-based study of metastatic colorectal cancer patients
  • 2022
  • Ingår i: British Journal of Cancer. - : Springer. - 0007-0920 .- 1532-1827. ; 126:1, s. 48-56
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Tumour-infiltrating CD3, CD8 lymphocytes and CD68 macrophages are associated with favourable prognosis in localised colorectal cancer, but the effect in metastatic colorectal cancer (mCRC) is not established.METHODS: A Scandinavian population-based cohort of non-resectable mCRC patients was studied. Tissue microarrays (n = 460) were stained with CD3, CD8 and CD68 using fluorescence-based multiplex immunohistochemistry. Associations with clinicopathological variables, overall survival (OS) and progression-free survival were estimated.RESULTS: Two-thirds of microsatellite instable (MSI) and one-fourth of microsatellite stable (MSS) tumours displayed the highest quartile density of CD8. For CD3 high vs low cases, median OS was 20 vs 16 months (HR: 0.76, 95% CI: 0.59, 0.76, p = 0.025) with 3-year OS of 27 vs 13%. For CD68 high vs low cases, median OS was 23 vs 15 months (HR: 0.69, 95% CI: 0.54, 0.88, p = 0.003) with 3-year OS of 28 vs 12%. MSI, BRAF mutation and CDX2 loss were negative prognostic markers independent of tumour immune infiltration.CONCLUSIONS: In mCRC, high lymphocyte infiltration was found in proportions of MSI and MSS tumours-potential subgroups of immunotherapy response. Tumour-infiltrating CD3 lymphocytes and CD68 macrophages were associated with median and long-term survival. MSI was a significant negative prognostic marker despite high immunogenicity.
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3.
  • Aasebö, Kristine Ö., et al. (författare)
  • Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors : A population-based cohort of metastatic colorectal cancer patients
  • 2019
  • Ingår i: Cancer Medicine. - : WILEY. - 2045-7634. ; 8:7, s. 3623-3635
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Immunotherapy for patients with microsatellite-instable (MSI-H) tumors or BRAF-inhibitors combination treatment for BRAF-mutated (mutBRAF) tumors in metastatic colorectal cancer (mCRC) is promising, but the frequency of these molecular changes in trial patients are low. Unselected population-based studies of these molecular changes are warranted.Methods: A population-based cohort of 798 mCRC patients in Scandinavia was studied. Patient and molecular tumor characteristics, overall survival (OS) and progression-free survival (PFS) were estimated.Results: Here, 40/583 (7%) tumor samples were MSI-H and 120/591 (20%) were mutBRAF; 87% of MSI-H tumors were mutBRAF (non-Lynch). Elderly (>75 years) had more often MSI-H (10% vs 6%) and MSI-H/mutBRAF (9% vs 4%) tumors. Response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first-line chemotherapy was all significantly lower in patients with MSI-H compared to patients with microsatellite stable tumors. MSI-H and mutBRAF were both independent poor prognostic predictors for OS (P = 0.049, P < 0.001) and PFS (P = 0.045, P = 0.005) after first-line chemotherapy. Patients with MSI-H tumors received less second-line chemotherapy (15% vs 37%, P = 0.005).Conclusions: In unselected mCRC patients, MSI-H and mutBRAF cases were more common than previously reported. Patients with MSI-H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third-line immunotherapy trial patients as they were older and most had mutBRAF tumor (non-Lynch).
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  • Cavalli-Björkman, Nina, 1970-, et al. (författare)
  • Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone
  • 2012
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 107:1, s. 189-194
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Socioeconomic status (SES) and social support influences cancer survival. If SES and social support affects cancer treatment has not been thoroughly explored. METHODS: A cohort consisting of all patients who were initially diagnosed with or who developed metastatic colorectal cancer (mCRC, n = 781) in three Scandinavian university hospitals from October 2003 to August 2006 was set up. Clinical and socioeconomic data were registered prospectively. RESULTS: Patients living alone more often had synchronous metastases at presentation and were less often treated with combination chemotherapy than those cohabitating (HR 0.19, 95% CI 0.04-0.85, P = 0.03). Surgical removal of metastases was less common in patients living alone (HR 0.29, 95% CI 0.10-0.86, P = 0.02) but more common among university-educated patients (HR 2.22, 95% CI 1.10-4.49, P = 0.02). Smoking, being married and having children did not influence treatment or survival. Median survival was 7.7 months in patients living alone and 11.7 months in patients living with someone (P < 0.001). Living alone remained a prognostic factor for survival after correction for age and comorbidity. CONCLUSION: Patients living alone received less combination chemotherapy and less secondary surgery. Living alone is a strong independent risk factor for poor survival in mCRC. 
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6.
  • Dahl, Olav, et al. (författare)
  • Evaluation of the stage classification of anal cancer by the TNM 8th version versus the TNM 7th version
  • 2020
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 59:9, s. 1016-1023
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The UICC TNM 7th edition introduced stage groups for anal cancer which in 2019 has not yet come into general use. The new TNM 8th edition from 2016 defines 7 sub-stages. Background data for these changes are lacking. We aimed to investigate whether the new classification for anal cancer reliably predict the prognosis in the different stages.Patients and methods: The Nordic Anal Cancer Group (NOAC) conducted a large retrospective study of all anal cancers in Norway, Sweden and most of Denmark in 2000–2007. From the Nordic cohort 1151 anal cancer patients with follow-up data were classified by the TNM 4th edition which has identical T, N and M definitions as the TNM 7th edition, and therefore also can be classified by the TNM 7th stage groups. We used the Nordic cohort to translate the T, N and M stages into the TNM 8th stages and sub-stages. Overall survival for each stage was assessed.Results: Although the summary stage groups for TNM 8th edition discriminates patients with different prognosis reasonably well, the analyses of the seven sub-stages show overlapping overall survival: HR for stage IIA 1.30 (95%CI 0.80–2.12) is not significantly different from stage I (p = .30) and HR for stage IIB 2.35 (95%CI 1.40–3.95) and IIIA 2.48 (95%CI 1.43–4.31) are also similar as were HRs for stage IIIB 3.41 (95%CI 1.99–5.85) and IIIC 3.22 (95%CI 1.99–5.20). Similar overlapping was shown for local recurrence and distant spread.Conclusion: The results for the sub-stages calls for a revision of the staging system. We propose a modification of the TNM 8th edition for staging of anal cancer into four stages based on the T, N and M definitions of the TNM 8th classification.
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7.
  • Dueland, Svein, et al. (författare)
  • Chemotherapy or Liver Transplantation for Nonresectable Liver Metastases From Colorectal Cancer?
  • 2015
  • Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 261:5, s. 956-960
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The primary objective was to compare overall survival (OS) in patients with colorectal cancer (CRC) with nonresectable liver-only metastases treated by liver transplantation or chemotherapy. Background: CRC is the third most common cancer worldwide. About 50% of patients will develop metastatic disease primarily to the liver and the lung. The majority of patients with liver metastases receive palliative chemotherapy, with a median OS of trial patients of about 2 years, and less than 10% are alive at 5 years. Methods: Patients with nonresectable liver-only CRC metastases underwent liver transplantation in the SECA study (n = 21). Disease-free survival (DFS) and OS of patients included in the SECA study were compared with progression-free survival (PFS) and OS in a similar cohort of CRC patients with liver-only disease included in a first-line chemotherapy study, the NORDIC VII study (n = 47). PFS/DFS and OS were estimated by the Kaplan-Meier method. Results: DFS/PFS in both groups were 8 to 10 months. However, a dramatic difference in OS was observed. The 5-year OS rate was 56% in patients undergoing liver transplantation compared with 9% in patients starting first-line chemotherapy. The reason for the large difference in OS despite similar DFS/PFS is likely different metastatic patterns at relapse/progression. Relapse in the liver transplantation group was often detected as small, slowly growing lung metastases, whereas progression of nonresectable liver metastases was observed in the chemotherapy group. Conclusions: Compared with chemotherapy, liver transplantation resulted in a marked increased OS in CRC patients with nonresectable liver-only metastases.
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  • Glimelius, Bengt, et al. (författare)
  • Persistent prevention of oxaliplatin-induced peripheral neuropathy using calmangafodipir (PledOx®) : a placebo-controlled randomised phase II study (PLIANT)
  • 2018
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 57:3, s. 393-402
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Oxaliplatin causes disabling acute and chronic peripheral neuropathy. We explored the preventive effects of calmangafodipir, mimicking the mitochondrial enzyme manganese superoxide dismutase, thereby protecting cells from oxidative stress, in a placebo-controlled, double-blinded randomised phase II study (ClinicalTrials.gov.NCT01619423) in patients with metastatic colorectal cancer (mCRC).Patient and methods: mCRC patients treated with modified FOLFOX-6 (folinic acid 200 mg/m2, 5-fluorouracil bolus 400 mg/m2, oxaliplatin 85 mg/m2 and 5-fluorouracil 2400 mg/m2 continuous infusion for 46 h) every fortnight for 8 cycles in first or second line were eligible. Calmangafodipir was given in a phase I dose-finding and in a phase II placebo-controlled study, as a 5-min infusion 10 min prior to oxaliplatin. Neurotoxicity was evaluated by the physician using the Oxaliplatin Sanofi Specific Scale and by the patient using the cold allodynia test and the Leonard scale.Results: Eleven patients were included in phase I without any detectable toxicity to calmangafodipir. In the phase II study, 173 patients were randomised to placebo (n = 60), calmangafodipir 2 µmol/kg (n = 57) and calmangafodipir 5 µmol/kg (n = 45, initially 10 µmol/kg, n = 11). Calmangafodipir-treated patients (all three doses pooled) had less physician graded neurotoxicity (odds ratio (90% confidence interval one-sided upper level) 0.62(1.15), p = .16), significantly less problems with cold allodynia (mean 1.6 versus 2.3, p < .05) and significantly fewer sensory symptoms in the Leonard scale (cycle 1–8 mean 1.9 versus 3.0, p < .05 and during follow-up after 3 and 6 months, mean 3.5 versus 7.3, p < .01). Response rate, progression-free and overall survival did not differ among groups.Conclusions: Calmangafodipir at a dose of 5 µmol/kg appears to prevent the development of oxaliplatin-induced acute and delayed CIPN without apparent influence on tumour outcomes.
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