| 51. |
- Glimelius, Bengt, et al.
(författare)
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Two countries - Two treatment strategies for rectal cancer
- 2016
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 121:3, s. 357-363
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Trials in rectal cancer have shown that radiotherapy (RT) decreases local recurrence rates, whereas the effects on survival are uncertain. Swedish and Norwegian oncologists have had different treatment recommendations. The aim was to evaluate local recurrence rates and survival in the two countries. Patients and methods: Between 1995 and 2012 rectal cancer patients registered in Sweden and Norway were analyzed, presenting population-based "real world" data. Results: Totally 29,029 Swedish and 15,456 Norwegian patients were analyzed. Resection for cure was performed in two-thirds of the patients. RT was given to 49% of Swedish patients, mainly short-course RT and to 26% of Norwegian patients, predominantly chemoradiotherapy (CRT). In Sweden, the proportion irradiated was stable whereas in Norway, an increase from 10% to 40% was seen. Local 5-year recurrence rates were initially higher in Norway (12%) than in Sweden (8%), whereas they were equally low (4%) during the latter time. No survival differences were seen, however, survival improved with time in both countries. Conclusions: Two entirely different approaches to preoperative therapy resulted in similar survival with initially higher local recurrence rates in Norway, but similarly low rates in later years. This raises questions about optimal RT rates and regimens.
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| 56. |
- Goey, Kaitlyn K. H., et al.
(författare)
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Consensus statement on essential patient characteristics in systemic treatment trials for metastatic colorectal cancer : Supported by the ARCAD Group
- 2018
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Ingår i: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 100, s. 35-45
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patient characteristics and stratification factors are key features influencing trial outcomes. However, there is substantial heterogeneity in reporting of patient characteristics and use of stratification factors in phase 3 trials investigating systemic treatment of metastatic colorectal cancer (mCRC). We aimed to develop a minimum set of essential baseline characteristics and stratification factors to include in such trials. Methods: We performed a modified, two-round Delphi survey among international experts with wide experience in the conduct and methodology of phase 3 trials of systemic treatment of mCRC. Results: Thirty mCRC experts from 15 different countries completed both consensus rounds. A total of 14 patient characteristics were included in the recommended set: age, performance status, primary tumour location, primary tumour resection, prior chemotherapy, number of metastatic sites, liver-only disease, liver involvement, surgical resection of metastases, synchronous versus metachronous metastases, (K)RAS and BRAF mutation status, microsatellite instability/mismatch repair status and number of prior treatment lines. A total of five patient characteristics were considered the most relevant stratification factors: RAS/BRAF mutation status, performance status, primary tumour sidedness and liver-only disease. Conclusions: This survey provides a minimum set of essential baseline patient characteristics and stratification factors to include in phase 3 trials of systemic treatment of mCRC. Inclusion of these patient characteristics and strata in study protocols and final study reports will improve interpretation of trial results and facilitate cross-study comparisons.
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| 57. |
- Goey, Kaitlyn K. H., et al.
(författare)
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Reporting of patient characteristics and stratification factors in phase 3 trials investigating first-line systemic treatment of metastatic colorectal cancer : A systematic review
- 2018
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 96, s. 115-124
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Forskningsöversikt (refereegranskat)abstract
- Background: Patient characteristics and stratification factors are important factors influencing trial outcomes. Uniform reporting on these parameters would facilitate cross-study comparisons and extrapolation of trial results to clinical practice. In 2007, standardisation on patient characteristics reporting and stratification in metastatic colorectal cancer (mCRC) trials was proposed. We investigated the reporting of prognostic factors and implementation of this proposal in mCRC trials published from 2005 to 2016.Methods: We searched PubMed and Embase (January 2005 – June 2016) for first-line phase 3 mCRC trials. Patient characteristics reporting and use of stratification factors were extracted and analysed for adherence to the proposal from 2007.Results: Sixty-seven trials (35,315 patients) were identified, reporting 48 different patient characteristics (median: 9 [range: 5–18] per study). Age, gender, performance status (PS), primary tumour site and adjuvant chemotherapy were frequently reported (87%–100%), in contrast to laboratory values, such as alkaline phosphatase, lactate dehydrogenase and white blood cell count (10%–25%). We identified 29 different stratification factors (median: 3 [range: 1–9] per study). The most common strata were PS and treatment centre (>60%). A median of 8/12 (range: 4–11) of the proposed parameters was reported. Although the percentage of studies reporting each factor slightly increased over time, there was no significant correlation between publication year and adherence to the proposal from 2007.Conclusions: We observed persistent heterogeneity in the reporting of patient characteristics and use of stratification factors in first-line mCRC trials. The proposal from 2007 has not led to increased uniformity of patient characteristics reporting and use of stratification over time. There is an urgent need to address this issue to improve the interpretation of trial results.
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| 58. |
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| 59. |
- Guren, Tormod Kyrre, et al.
(författare)
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Cetuximab in treatment of metastatic colorectal cancer : final survival analyses and extended RAS data from the NORDIC-VII study
- 2017
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Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 116:10, s. 1271-1278
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Tidskriftsartikel (refereegranskat)abstract
- Background: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival analysis with BRAF and extended RAS mutational status, 5 years after the primary analysis.Methods: A total of 566 patients were included in the intention-to-treat (ITT) population of the NORDIC-VII study. Updated survival status was obtained from 176 patients who were alive in the primary survival analyses. Samples from 223 tumours previously found to be KRAS (exon 2) and BRAF (V600E) wild-type, were re-analysed for KRAS (exons 3 and 4) and NRAS (exons 2-4) mutations.Results: Including the extended RAS analyses, RAS and BRAF mutational status was available from 457 patients (81% of the ITT population). RAS was mutated in 46% and BRAF in 12% of the tumours. RAS and BRAF, if mutated, were negative prognostic factors. The updated analyses confirmed the finding of the primary report that cetuximab did not provide any additional benefit when added to FLOX in patients with RAS/BRAF wild-type tumours, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy.Conclusions: Adding cetuximab to Nordic FLOX did not provide any clinical benefit, but the data suggested an effect of cetuximab monotherapy in patients with RAS/BRAF wild-type tumours in the NORDIC-VII cohort. The data were compatible with a negative interaction between cetuximab and the Nordic FLOX chemotherapy backbone.
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| 60. |
- Hamfjord, J., et al.
(författare)
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Total circulating cell-free DNA as a prognostic biomarker in metastatic colorectal cancer before first-line oxaliplatin-based chemotherapy
- 2019
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:7, s. 1088-1095
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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