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- Tarpgaard, Line S., et al.
(författare)
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Intact and cleaved plasma soluble urokinase receptor in patients with metastatic colorectal cancer treated with oxaliplatin with or without cetuximab
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:10, s. 2470-2477
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Tidskriftsartikel (refereegranskat)abstract
- Circulating forms of the urokinase plasminogen activator receptor (uPAR) are associated with prognosis in patients with colorectal cancer. Preclinical studies have shown that uPAR can influence the state of phosphorylation and signalling activity of the epidermal growth factor receptor (EGFR) in a ligand-independent manner. The purpose of the study was to evaluate whether plasma soluble intact and cleaved uPAR(I-III) + (II-III) levels could identify a subpopulation of patients with metastatic colorectal cancer (mCRC) where treatment with cetuximab would have a beneficial effect. Plasma samples were available from 453 patients treated in the NORDIC VII study. Patients were randomized between FLOX and FLOX + cetuximab. The levels of uPAR(I-III) 1(II-III) were determined by time-resolved fluorescence immunoassay. We demonstrated that higher baseline plasma uPAR(I-III) 1(II-III) levels were significantly associated with shorter progression-free survival (PFS) (HR51.30, 1.14-1.48, p=0.0001) and overall survival (OS) (HR51.75, 1.52-2.02, p < 0.0001). Multivariate Cox analysis showed that plasma uPAR(I-III) 1(II-III) was an independent biomarker of short OS (HR51.45, 1.20-1.75, p=0.0001). There were no significant interactions between plasma uPAR(I-III) 1(II-III) levels, KRAS mutational status and treatment either PFS (p=0.43) or OS (p=0.095). However, further explorative analyses indicated that patients with low levels of circulating suPAR and a KRAS wild-type tumor have improved effect from treatment with FLOX+cetuximab as compared to patients with KRAS wild-type and high levels of suPAR. These results thus support the preclinical findings and should be further tested in an independent clinical data set.
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| 2. |
- Dueland, Svein, et al.
(författare)
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Chemotherapy or Liver Transplantation for Nonresectable Liver Metastases From Colorectal Cancer?
- 2015
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 261:5, s. 956-960
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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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