Kinetics of postdiagnosis platelet count with overall survival of pancreatic cancer: a counting process approach.
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ABSTRACT:
SUBMITTER: Xiao Y
PROVIDER: S-EPMC4864817 | biostudies-other | 2016 May
REPOSITORIES: biostudies-other
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Project description:Thrombocytosis is associated with cancer progression and death for many cancer types. It is unclear if platelet count is also associated with cancer survival. We conducted a cohort study of 112,231 adults in Ontario with a diagnosis of cancer between January 2007 and December 2016. We included patients who had a complete blood count (CBC) completed in the 30 days prior to their cancer diagnosis. Subjects were assigned to one of three categories according to platelet count: low (≤25th percentile), medium (>25 to <75th percentile), and high (≥75th percentile). Study subjects were followed from the date of their cancer diagnosis for cancer-specific death. Of the 112,231 eligible cancer patients in the cohort study, 40,329 (35.9%) died from their cancer in the follow-up period. Relative to those with a medium platelet count, the rate of cancer-specific death was higher among individuals with a high platelet count (HR 1.52; 95%CI 1.48-1.55) and was lower among individuals with a low platelet count (HR 0.91; 95%CI 0.88-0.93). A high platelet count was associated with poor survival for many cancer types. Platelet count could potentially be used as a risk stratification measure for cancer patients.
| S-EPMC8833779 | biostudies-literature
Project description:ObjectivesTo explore the non-linear relationship between platelet count (PLT) and hepatocellular carcinoma (HCC) overall survival (OS).SettingThe study was done in Sun Yat-sen University Cancer Center (SYSUCC) from January 2007 to May 2012, a total of 5005 consecutive participants at SYSUCC were retrospectively reviewed, and 979 patients with Barcelona clinic liver cancer (BCLC) stage B were selected for the final analysis.ParticipantsA total of 979 newly diagnosed patients with HCC with BCLC stage B were identified for the secondary analysis. Eight cases were excluded for missing data of PLT.Main outcome measuresCox proportional hazard regression models were used to calculate multivariable-adjusted HRs and 95% CIs for HCC. The non-linear relationship was estimated through a restricted cubic spline regression, and a two-piecewise Cox proportional hazards model was further performed to calculate the threshold effect. We used multiple imputation to deal with the missing data.ResultsIn the multivariate analysis, Log PLT was associated with a 91% risk increase in death (HR 1.91; 1.28 to 2.85) with adjustment for gender, Child-Pugh class, age × diameter of main tumour, both lobe with lesions × number of the intrahepatic lesions, alpha-fetoprotein (<25, ≥25) and lactic dehydrogenase (<245, ≥245). We also found a U-shape relationship between PLT and HCC OS at the inflexion point of 67.6×109/L. The HR was 0.12 (95% CI 0.03 to 0.52) for Log PLT≤10.83 and 3.07 (CI 1.91 to 4.92) for Log PLT>10.83 after adjusting for potential confounders. The core results were consistent with those from the sensitivity analysis. Besides, a significantly higher hazard risk was found in the patients with age <55, both lobes with lesions, tumour diameter >50, haemoglobin ≥120 and C reactive protein >10.ConclusionPLT was nonlinearly associated with HCC OS.
| S-EPMC7651714 | biostudies-literature
Project description:BackgroundPlatelets have been reported to influence tumor biology and may promote metastasis. Traditionally, thrombocytopenia, a hallmark of cirrhosis, was associated with hepatocellular carcinoma (HCC) development. However, the impact of platelet count on outcome in patients with established HCC is not well studied.MethodsOutcomes of patients with cirrhosis diagnosed with HCC between 1995 and 2013 (derivation cohort) and 2000-2016 (validation cohort) who were not eligible for surgical treatment and did not receive antiplatelet therapy were retrospectively studied. Thrombocytopenia was defined as platelet count < 150 g/L. High mean platelet volume (MPV) was defined as ≥median value of the respective cohort (derivation cohort: ≥11 fL; validation cohort: ≥10.6 fL).ResultsAmong 626 patients with unresectable HCC, thrombocytopenia was present in 378 (60.4%) and was associated with favorable baseline tumor characteristics: lower diameter of the largest nodule (5.6 ± 3.2 vs. 7.6 ± 4.2 cm), less extrahepatic spread (9.5 vs. 20.2%, both p < 0.001), less macrovascular invasion (21.2 vs. 31.0%, p = 0.005), and lower BCLC stages (63.0 vs. 73.4% BCLC C/D; p = 0.007) as compared to patients with normal platelet count. On univariate analysis, thrombocytopenia and larger MPV were associated with longer overall survival (OS) (thrombocytopenia: median OS [95% CI], 11.5 [9.3-13.8] vs. 5.5 [3.8-7.1] months; p = 0.001; MPV ≥11 fL: 11.7 [9.1-14.2] vs. 6.0 [4.4-7.6] months; p < 0.001). In multivariate analysis, the combined variable of thrombocytopenia and larger MPV was independently associated with longer OS (HR [95% CI], 0.80 [0.65-0.98]; p = 0.029). These results were confirmed in an independent external validation cohort of 525 patients with cirrhosis and HCC. Again, patients with thrombocytopenia and high MPV had significantly longer OS (15.3 [11.7-18.9] vs. 9.3 [7.4-11.2] months; p < 0.001).ConclusionsThrombocytopenia and higher MPV are associated with better outcome in patients with advanced HCC. These findings may prompt further clinical research on additive antiplatelet therapy in the prevention and management of HCC.
| S-EPMC6547277 | biostudies-literature
Project description:To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART.SMART patients from sites that determined platelets routinely.Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2.Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: -24 000/?l (-54 000 to 4000) vs. 3000 (-22 000 to 24 000), respectively, P < 0.0001)] and the rate of developing thrombocytopenia (<100 000/?l) was significantly higher in the drug conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2-2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = -0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels.Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study.
| S-EPMC4024440 | biostudies-literature
Project description:PurposeTo evaluate the relationship between serum CA19-9 and overall survival in patients with advanced pancreatic cancer.Methods109 advanced pancreatic cancer patients with gemcitabine based first-line chemotherapy were included. The effect of pretreatment CA19-9 level on overall survival was modeled by Cox proportional hazard regression. The effect of CA19-9 kinetics on overall survival was modeled by an extended Cox regression with a time varying coefficient and a time varying covariate.ResultsUnivariate analysis indicated that baseline CA19-9 correlated with OS (HR = 1.66, p < 0.01) and this association remained significant within multivariate analysis (HR = 1.56, P < 0.01). For the analysis of CA19-9 kinetics, the extended Cox model showed that the effect of CA19-9 on overall survival changed with time: increased in the first two months and reached the top at a HR of about 2, then decreased for the next two months to a HR of about 1.56 and finally tended to be stable. The combination of pretreatment CA19-9 and CA19-9 at 2 month may better evaluate the patients' prognosis compared to pretreatment CA19-9 alone.ConclusionPretreatment CA19-9 and CA19-9 kinetics may serve as a useful serum biomarker in advanced pancreatic cancer.
| S-EPMC5444714 | biostudies-literature
Project description:Prognosis of lower-risk (International Prognostic Scoring System [IPSS] low/intermediate-1) myelodysplastic syndrome (MDS) is heterogeneous and relies on steady-state assessment of cytopenias. We analyzed relative drops in neutrophil and platelet counts during the first 6 months of follow-up of lower-risk MDS patients. We performed a landmark analysis of overall survival (OS) of lower-risk MDS patients prospectively included in the European LeukaemiaNet MDS registry having a visit at 6 ± 1 month from inclusion to assess the prognostic relevance of relative drops in neutrophils and platelets, defined as (count at landmark - count at inclusion)/count at inclusion. Of 2102 patients, 807 were eligible for the stringent 6-month landmark analysis. Median age was 73 years. Revised IPSS was very low, low, and intermediate/higher in 26%, 43%, and 31% of patients, respectively. A relative drop in platelets >25% at landmark predicted shorter OS (5-year OS, 21.9% vs 48.6% with platelet drop ≤25%, P < 10-4), regardless of baseline IPSS-revised or absolute platelet counts. Relative neutrophil drop >25% had no significant impact on OS. We built a classifier based on red blood cell transfusion dependence (RBC-TD) and relative platelet drop >25% at landmark. Patients with none (62%), either (27%), or both criteria (11%) had 5-year OS of 53.3%, 32.7%, and 9.0%, respectively (P < 10-4). This classifier was validated in an independent cohort of 335 patients. Combining relative platelet drop >25% and RBC-TD at 6 months from diagnosis provides an inexpensive and noninvasive way to predict outcome in lower-risk MDS. This study was registered at www.clinicaltrials.gov as #NCT00600860.
| S-EPMC6113605 | biostudies-literature
Project description:BackgroundPancreatic carcinoma is one of the most lethal human cancers. In patients with resectable tumors, surgery followed by adjuvant chemotherapy is the only curative treatment. However, the 5-year survival is 20%. Because of a strong metastatic propensity, neoadjuvant chemotherapy is being tested in randomized clinical trials. In this context, improving the selection of patients for immediate surgery or neoadjuvant chemotherapy is crucial, and high-throughput molecular analyses may help; the present study aims to address this.MethodsClinicopathological and gene expression data of 695 pancreatic carcinoma samples were collected from nine datasets and supervised analysis was applied to search for a gene expression signature predictive for overall survival (OS) in the 601 informative operated patients. The signature was identified in a learning set of patients and tested for its robustness in a large independent validation set.ResultsSupervised analysis identified 1400 genes differentially expressed between two selected patient groups in the learning set, namely 17 long-term survivors (LTS; ≥ 36 months after surgery) and 22 short-term survivors (STS; dead of disease between 2 and 6 months after surgery). From these, a 25-gene prognostic classifier was developed, which identified two classes ("STS-like" and "LTS-like") in the independent validation set (n = 562), with a 25% (95% CI 18-33) and 48% (95% CI 42-54) 2-year OS (P = 4.33 × 10-9), respectively. Importantly, the prognostic value of this classifier was independent from both clinicopathological prognostic features and molecular subtypes in multivariate analysis, and existed in each of the nine datasets separately. The generation of 100,000 random gene signatures by a resampling scheme showed the non-random nature of our prognostic classifier.ConclusionThis study, the largest prognostic study of gene expression profiles in pancreatic carcinoma, reports a 25-gene signature associated with post-operative OS independently of classical factors and molecular subtypes. This classifier may help select patients with resectable disease for either immediate surgery (the LTS-like class) or neoadjuvant chemotherapy (the STS-like class). Its assessment in the current prospective trials of adjuvant and neoadjuvant chemotherapy trials is warranted, as well as the functional analysis of the classifier genes, which may provide new therapeutic targets.
| S-EPMC5606023 | biostudies-literature
Project description:ObjectivePlatelets have been implicated in cancer metastasis and prognosis. No population-based study has been reported as to whether preoperative platelet count directly predicts metastatic recurrence of colorectal cancer (CRC) patients.DesignUsing a well-characterized cohort of 1,513 surgically resected CRC patients, we assessed the predictive roles of preoperative platelet count in overall survival, overall recurrence, as well as locoregional and distant metastatic recurrences.ResultsPatients with clinically high platelet count (≥400 × 10(9)/L) measured within 1 month before surgery had a significantly unfavorable survival (hazard ratio [HR] = 1.66, 95 % confidence interval [CI] 1.34-2.05, P = 2.6 × 10(-6), P(log rank) = 1.1 × 10(-11)) and recurrence (HR = 1.90, 1.24-2.93, P = 0.003, P(log rank) = 0.003). The association of platelet count with recurrence was evident only in patients with metastatic (HR = 2.81, 1.67-4.74, P = 1.1 × 10(-4), P(log rank) = 2.6 × 10(-6)) but not locoregional recurrence (HR = 0.59, 95 % CI 0.21-1.68, P = 0.325, P(log rank) = 0.152). The findings were internally validated through bootstrap resampling (P < 0.01 at 98.6 % of resampling). Consistently, platelet count was significantly higher in deceased than living patients (P < 0.0001) and in patients with metastatic recurrence than locoregional (P = 0.004) or nonrecurrent patients (P < 0.0001). Time-dependent modeling indicated that the increased risks for death and metastasis associated with elevated preoperative platelet counts persisted up to 5 years after surgery.ConclusionOur data demonstrated that clinically high level of preoperative platelets was an independent predictor of CRC survival and metastasis. As an important component of the routinely tested complete blood count panel, platelet count may be a cost-effective and noninvasive marker for CRC prognosis and a potential intervention target to prevent metastatic recurrence.
| S-EPMC3748145 | biostudies-literature
Project description:An elevated platelet count has been associated with an increased incidence of cancer and poor survival for many cancer types. In this study, platelet levels were captured among cancer patients in the 2 years prior to and following a cancer diagnosis. I investigated if the trends in platelet count differ between patients that died or did not die from their cancer. For many cancer types, including colon, lung, ovary, and stomach, platelet counts rose as they approached the date of diagnosis. Patients that died from their cancer within 3 years of diagnosis had a higher peak platelet count than those who survived. Following diagnosis, platelet count was elevated among patients that died from their cancer as compared to patients who survived. An elevated platelet count could potentially indicate the presence of an occult cancer or be used as a prognostic measure for cancer-specific survival.
| S-EPMC8944120 | biostudies-literature
Project description:BackgroundMutations in the KRAS gene can be detected in about 70-90% of pancreatic cancer (PC) cases. Whether these mutations have a prognostic or predictive value remains elusive. Furthermore, the clinical relevance of the extended RAS (KRAS+NRAS) mutational status is unclear in PC.MethodsWe prospectively defined a PC patient population who received erlotinib-free chemotherapy regimens. A statistically significant difference between KRAS wild-type and KRAS mutated tumours in at least 160 patients in this population would support the assumption of a rather prognostic role of KRAS.ResultsOne hundred and seventy-eight tumour samples were collected from prospective clinical studies and successfully analysed for the extended RAS status: 37 tumours were KRAS wild-type (21%), whereas 141 (79%) carried a KRAS mutation; 132 of these mutations were found in KRAS exon 2 (74%), whereas only 9 mutations (5%) were detected in KRAS exon 3. Within KRAS exon 4 and NRAS exons 2-4, no mutations were apparent. There was no significant difference in overall survival for KRAS wild-type vs mutant patients (9.9 vs 8.3 months, P=0.70).ConclusionsTogether with the results of the AIO-PK-0104-trial, the present analysis supports the notion that KRAS mutation status is rather predictive than prognostic in advanced PC.
| S-EPMC5520094 | biostudies-literature