PurposePancreatic cancer is an aggressive solid tumor with a severe prognosis. Although tumor biomarkers are often used to identify advanced pancreatic cancer, this is not accurate, and the currently used biomarkers are not indicative of prognosis. The present study evaluated circulating tumor DNA (ctDNA) as a biomarker for prognosis prediction and disease monitoring in metastatic pancreatic adenocarcinoma (PAC).MethodsFrom 2017 to 2018, 40 patients with metastatic PAC were enrolled, and tumor tissue and blood samples were collected from 40 and 35 patients, respectively. CtDNA was sequenced by next-generation sequencing (NGS) with a 425-gene capture panel. The association of clinical characteristics, laboratory indicators, and dynamic ctDNA with patient outcomes was analyzed.ResultsMutations in KRAS (87.5%, N = 35) and TP53 (77.5%, N = 31) were most common in 40 tumor tissue. Patients’ ECOG score, CA19-9, CEA, neutrophil-lymphocyte ratio (NLR), platelet- lymphocyte ratio (PLR) levels and mutations in ≥ 3 driver genes were strongly correlated with patients’ overall survival (OS). Patients’ gender, ECOG score, CA19-9, and CEA levels were associated with progression-free survival (PFS) (P<0.05). In 35 blood samples, univariate analysis showed a significant association between ECOG score, CA19-9, KRAS or CDKN2A mutation in ctDNA and OS and between CA19-9, CDKN2A or SMAD4 mutation in ctDNA and PFS. Cox hazard proportion model showed that patients’ CDKN2A mutation in ctDNA (HR=16.1, 95% CI=4.4-59.1, P<0.001), ECOG score (HR=6.2, 95% CI=2.4-15.7, P<0.001) and tumor location (HR=0.4, 95% CI=0.1-0.9, P=0.027) were significantly associated with OS. Patients’ CDKN2A mutation in ctDNA (HR=6.8, 95% CI=2.3-19.9, P=0.001), SMAD4 mutation in ctDNA (HR=3.0, 95% CI=1.1-7.9, P=0.031) and metastatic organ (HR=0.4, 95% CI=0.2-1.0, P=0.046) were significantly associated with PFS. Longitudinal changes in gene mutation allelic frequency (MAF) value were evaluated in 24 patients. Detection of progression disease (PD) by ctDNA was 0.9 months earlier than by radiological imaging (mean PFS: 4.6m vs 5.5m, P=0.004, paired t-test).ConclusionsThe ctDNA has the potential as a specific survival predictive marker for metastatic PAC patients. Longitudinal ctDNA tracking could potentially help identify disease progression and be a valuable complement for routine clinical markers and imaging.
Aims The preoperative serum levels of inflammatory mediators, including C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), have been demonstrated to be correlated with patient outcomes in colorectal cancer (CRC); however, the prognostic role of these levels has been less well-studied in postoperative settings. Materials and methods A total of 122 stage I-III CRC patients were retrospectively enrolled. Serum levels of CRP, PCT and IL-6 were measured after surgery, and their prognostic value was evaluated. Kaplan-Meier analysis was used to determine the differences in disease-free survival (DFS) and overall survival (OS) between patients with different levels of these mediators, and the Cox proportional hazards model was used to estimate the risk factors. Results In contrast to CRP and PCT, only the level of IL-6 was significant in predicting DFS (P = 0.01) but not OS (P = 0.07). A total of 66.39% (81/122) of patients were assigned to the low IL-6 group and no significant differences were found in the collected clinicopathological parameters among the low or high IL-6 subgroups. The level of IL-6 was negatively correlated with postoperative (1 w) (R=-0.24, P = 0.02) absolute lymphocyte counts. Patients with low levels of IL-6 had better DFS (log rank = 6.10, P = 0.01) but not OS (log rank = 2.28, P = 0.13). Finally, the level of IL-6 was an independent risk factor for DFS (HR: 1.81, 95% CI: 1.03–3.15, P = 0.04). Conclusions Compared to CRP and PCT, the level of IL-6 was observed to be the only significant factor in predicting the prognosis of stage I-III CRC patients after surgery, and a low level of IL-6 was associated with good DFS.
Aims Adjuvant chemotherapy (ACT) plays an important role in improving the survival of stage II-III colorectal cancer (CRC) patients after curative surgery. However, the prognostic role of irregular delay of ACT (IDacT) for these patients has been less studied. Materials and methods A total of 117 stage II-III CRC patients who underwent radical resection and received at least 3 months ACT were enrolled retrospectively. The significance of IDacT, including total delay (TD) and delay per cycle (DpC), in predicting disease-free survival (DFS) was determined using receiver operating characteristic curve (ROC) analysis. The survival differences between the TD, DpC-short and DpC-long subgroups were tested using Kaplan–Meier analysis, and risk factors for prognosis were determined using a Cox proportional hazards model. Results Using 35.50 and 3.27 days as the optimal cut-off points for TD and DpC, respectively, ROC analysis revealed that TD and DpC had sensitivities of 43.60% and 59.00% and specificities of 83.30% and 62.80%, respectively, in predicting DFS (both P < 0.05). No differences in the clinicopathological parameters were found between the TD, DpC-short or -long subgroups except histological differentiation in different TD subgroups and combined T stages in different DpC subgroups (both P = 0.04). Patients in the TD or DpC-long group exhibited significantly worse survival than in the -short group (TD: Log rank = 9.11, P < 0.01; DpC: Log rank = 6.09, P = 0.01). DpC was an independent risk factor for prognosis (HR = 2.54, 95% CI: 1.32–4.88, P = 0.01). Conclusions IDacT had a profound effect on the outcome for stage II-III CRC. Although TD and DpC were significant for the prognosis, DpC was more robust, and patients who presented DpC for a long time had a significantly worse DFS.
Background: Preoperative serum albumin (ALB) and carcinoembryonic antigen (CEA) were useful prognostic factors in colorectal cancer (CRC); however, the ALB to CEA ratio (ACR) and their individual prognostic efficacies have been less studied. Methods: A retrospective study with 156 CRC patients staged I to IV was performed. The prognostic efficacy of ACR was estimated and subsequently compared with ALB, CEA, and other systemic inflammation markers, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). Differences in progression-free survival (PFS) and overall survival (OS) were determined by Kaplan–Meier (K-M) analysis, and the risk factors for survival were calculated by the Cox proportional hazards model. Results: A total of 31.41% (49 of 156) of patients presented with ACR-low disease, and these patients had tumors with advanced T stages, larger tumor diameters and distant metastases, and a lower LMR. When 5.98 was used as the cut-off point, it had a sensitivity of 58.50% and 61.50% and a specificity of 83.50% and 80.50% for PFS and OS, respectively. ACR displayed a superior prognostic efficacy than individual ALB, CEA and NLR, LMR, and PLR for both PFS and OS (except LMR). Patients in the ACR-low group displayed significantly worse PFS and OS than those in the ACR-high group. Finally, ACR was an independent prognostic factor for both PFS (HR = 0.31, 95% CI: 0.17−0.56, P < .01) and OS (HR = 0.33, 95% CI: 0.16−0.66, P < .01). Conclusions: ACR was a robust prognostic factor in CRC, and patients with a relatively low preoperative ACR would have significantly worse survival.
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