Usefulness of plasma D-dimer level for monitoring development of distant organ metastasis in colorectal cancer patients after curative resection [Corrigendum]

Abstract Introduction Venous thromboembolism is a frequent complication in cancer patients and results in a considerable morbidity and mortality. The underlying mechanisms leading to the increased thrombotic risk are yet poorly understood. We have previously shown that levels of extracellular vesicles (EV) are elevated in patients with colorectal cancer compared to healthy control individuals (Hron et al, Thromb Haemost 2007;97:119-123). EV originate from blood or endothelial cells, or from the underlying tumor itself. They may contribute to coagulation activation and propagation by exposing tissue factor and by providing a surface for the interaction of coagulation factors. In that study, the number of EV was also positively correlated with levels of D-dimer, a fibrin split product and marker of coagulation activation. We hypothesize that number of EV and levels of D-dimer decline with decreasing tumor load during antineoplastic treatment. Therefore, the study aims at evaluating the long-term effect of chemotherapy on hemostatic system activation in patients with advanced colorectal cancer. Methods We conducted a pilot study including patients receiving chemotherapy because of advanced colorectal cancer. All chemotherapy regimens were based on 5-fluorouracilcombined with either oxaliplatin or irinotecan without or with an antibody (bevacizumab in 72%, cetuximab in 11%, and ramucirumab in 5% of patients, respectively). Patients were followed for 3 chemotherapy cycles. The study was approved by the local ethics committee, was conducted according to the Declaration of Helsinki and informed consent was obtained from all study patients. Venous blood was sampled at each cycle immediately before chemotherapy and was centrifuged at 2600 g for 15 minutes. The number of EV was assessed by flow cytometry using a FACSCalibur® flow cytometer with CellQuest™ software (Becton Dickinson) immediately after blood collection and centrifugation in fresh plasma. EV were defined by size (forward scatter, <1 µm) and annexin V binding. Tissue factor positive EV were characterized by an anti-CD142 antibody. Plasma was then frozen and stored at -80°C and was used for determination of markers of coagulation activation (D-dimer, prothrombin fragment f1.2) by commercially available ELISA kits. All outcome variables were log-transformed due to skewed distributions. The paired t-test was used to compare baseline (before the 1st chemotherapy) levels with measurements obtained from the 2nd and 3rd blood sampling. In order to provide a clearer legibility, all data is presented in absolute numbers and all values are given as median (quartiles) if not otherwise stated. Results 18 patients completed 3 cycles of chemotherapy. Their mean (± SD) age was 60.5 (± 12.2) years and 14 (78%) were men. None of the patients developed venous thromboembolism. Table 1 shows the levels of coagulation activation markers and the number of EV at baseline and before the 2nd and 3rd cycle of chemotherapy, respectively. D-dimer levels were 1.22 (0.42-2.31) µg mL-1 at baseline and significantly decreased over the course of treatment. D-dimer levels did not correlate with the number of EV either at baseline or at later time points. The number of EV decreased from 474 (312-617) x 103 mL-1 at baseline to 359 (239-474) x 103 mL-1 before the 3rd cycle. The proportion of tissue factor positive EV was small at baseline and throughout treatment. Levels of prothrombin fragment f1.2 did not change during treatment and did not correlate with number of EV at any time point. Conclusions In patients with advanced colorectal cancer chemotherapy attenuates coagulation activation as indicated by a decline of D-dimer levels and number of EV. These findings warrant further studies in a larger patient population and longer observation time. Table 1 Number of extracellular vesicles (EV) and markers of coagulation activation in plasma of colorectal cancer patients before and during chemotherapy Table 1. Number of extracellular vesicles (EV) and markers of coagulation activation in plasma of colorectal cancer patients before and during chemotherapy Disclosures No relevant conflicts of interest to declare.

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Association of total hysterectomy with survival among newly diagnosed uterine cancer patients with distant organ metastasis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5583 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5583-5583

Author(s):

Yuefeng Wang ◽

Todd D. Tillmanns ◽

Michael Farmer ◽

Lillian Rinker ◽

Bradley G. Somer ◽

...

Keyword(s):

Survival Analysis ◽

Propensity Score ◽

Cancer Patients ◽

Uterine Cancer ◽

Rank Test ◽

Newly Diagnosed ◽

Pelvic Radiotherapy ◽

Distant Organ Metastasis ◽

Organ Metastasis ◽

Distant Organ

5583 Background: There is growing evidence that definitive local therapies (surgery or radiotherapy) may increase patient’s survival for some types of metastatic cancers. However, the role of total abdominal hysterectomy (TAH) for newly diagnosed uterine cancer with distant organ metastasis has not been established. The objective of this study is to determine the potential overall survival (OS) benefit associated with TAH for distant metastatic uterine cancer. Methods: The National Cancer Database was analyzed to evaluate OS for newly diagnosed uterine cancer patients with metastasis to brain, lung, liver, bone or distant lymph node, treated with chemotherapy with or without TAH. Those without treatment, treated with definitive pelvic radiotherapy, or without baseline variables were excluded. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. In order to control the selection biases, we performed Landmark analysis, and survival analysis by the sequence of chemotherapy and TAH. Separate survival analysis was performed for patients who received chemotherapy plus definitive pelvic radiotherapy (RT) or chemotherapy plus TAH and definitive pelvic RT. Results: From 2010 to 2014, 1,809 uterine cancer patients with distant organ metastasis received chemotherapy alone and 1,388 patients received chemotherapy plus TAH. At a median follow-up of 13.4 months, addition of TAH to chemotherapy was associated with improved survival on univariate (HR 0.57; P < 0.001) and multivariate analysis (HR 0.59; P < 0.001) compared to chemotherapy alone. Propensity score-matched analysis demonstrated superior median survival (19.8 vs 11.0 months) and 2-year OS (44% vs 28%) with TAH (multivariate HR 0.59; P < 0.001). Landmark analyses limited to long-term survivors of ≥0.5, ≥1, and ≥2 years showed improved OS with TAH in all subsets (all P < 0.05). The benefit of TAH was present among not only those involving one metastatic site (HR 0.59; P < 0.001), but also those involving multiple metastatic sites (HR 0.60; P < 0.001). Separate survival analyses showed chemotherapy plus definitive pelvic RT or chemotherapy plus TAH and RT were both superior to chemotherapy alone. Conclusions: In this large contemporary analysis, uterine cancer patients with distant organ metastasis receiving TAH and chemotherapy had substantial longer survival than patients treated with chemotherapy alone. Prospective trials evaluating TAH for metastatic uterine cancer are warranted.

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