Postoperative serum tumor markers-based nomogram predicting early recurrence for patients undergoing radical resections of pancreatic ductal adenocarcinoma.

Early recurrence (ER) after surgical resection is an important factor that impacts the survival of patients with pancreatic ductal adenocarcinoma (PDA). We examined risk factors for ER after PDA resection. One hundred and thirteen PDA patients who underwent R0 or R1 resection were retrospectively analyzed. Thirty-four patients (30.1%) received neoadjuvant chemotherapy (NAC) for borderline resectable (BR) (n=13) or initially unresectable (n=21) disease. ER was defined as that diagnosed within 6 months after surgery. Receiver operating characteristic analysis was performed for each variable to determine the optimal cutoff value. ER occurred in 21 patients (18.6%). In univariate analysis, preoperative platelet-to-lymphocyte ratio (PLR) ≥144, carbohydrate antigen (CA) 19-9 ≥162 U/mL, and pathological tumor size ≥3 cm were significantly associated with ER. High PLR and CA19-9 were independent risk factors for ER by multivariate analysis. Area under the curve (AUC) for predicting ER from a combination of PLR and CA19-9 was 0.765 (95% confidence interval: 0.664-0.866), which increased the AUC compared to that for each risk factor alone. Patients with both risk factors had a significantly worse overall survival than those with one or no risk factors. When 24 patients with BR-PDA were considered, NAC was associated with a reduced likelihood of having risk factors and with a low ER rate. A combination of PLR and CA19-9 is a useful predictor of ER after macroscopic curative resection for PDA. NAC may reduce the risk of ER in selected patients.

Pancreatectomy with concomitant portomesenteric vein resection (PVR) enables patients with portomesenteric vein (PV) involvement to achieve radical resection of pancreatic ductal adenocarcinoma, however, early recurrence (ER) is frequently observed. To predict ER and identify patients at high risk of ER for individualized therapy. Totally 238 patients undergoing pancreatectomy and PVR were retrospectively enrolled and were allocated to the training or validating cohort. Univariate Cox and LASSO regression analyses were performed to construct serum recurrence score (SRS) based on 26 serum-derived parameters. Uni- and multivariate Cox regression analyses of SRS and 18 clinicopathological variables were performed to establish a Nomogram. Receiver operating characteristic curve analysis was used to evaluate the predictive accuracy. Survival analysis was performed using Kaplan-Meier method and log-rank test. Independent serum-derived recurrence-relevant factors of LASSO regression model, including postoperative carbohydrate antigen 19-9, postoperative carcinoembryonic antigen, postoperative carbohydrate antigen 125, preoperative albumin (ALB), preoperative platelet to ALB ratio, and postoperative platelets to lymphocytes ratio, were used to construct SRS [area under the curve (AUC): 0.855, 95%CI: 0.786-0.924]. Independent risk factors of recurrence, including SRS [hazard ratio (HR): 1.688, 95%CI: 1.075-2.652], pain (HR: 1.653, 95%CI: 1.052-2.598), perineural invasion (HR: 2.070, 95%CI: 0.827-5.182), and PV invasion (HR: 1.603, 95%CI: 1.063-2.417), were used to establish the recurrence nomogram (AUC: 0.869, 95%CI: 0.803-0.934). Patients with either SRS > 0.53 or recurrence nomogram score > 4.23 were considered at high risk for ER, and had poor long-term outcomes. The recurrence scoring system unique for pancreatectomy and PVR, will help clinicians in predicting recurrence efficiently and identifying patients at high risk of ER for individualized therapy.

BackgroundGiven the poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC), the accurate stratification of patients at high risk for early recurrence (ER) is an urgent need. Conventional predictors such as carbohydrate antigen 19-9 (CA19-9) and tumor diameter have suboptimal efficacy. Quantitative parameters derived from dual-energy computed tomography (DECT) and the 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) serve as validated imaging biomarkers for aggressive tumor biology. This study aimed to develop an integrative nomogram that combines these imaging markers with clinicopathological factors to preoperatively predict ER in resectable PDAC.MethodsIn this single-center retrospective study, we analyzed 80 patients diagnosed with pathologically confirmed PDAC from November 2021 to July 2023. ER was defined as disease relapse within 12 months postoperatively, and patients were categorized into ER and non-early recurrence (non-ER) groups. Clinicopathological variables, including tumor markers, pathological T stage (pTs), pathological N stage (pNs), tumor location, maximum tumor diameter, perineural invasion (PNI), and lymphovascular invasion (LVI), were collected. The following preoperative DECT parameters were obtained: dual-energy index (DEI), effective atomic number (Zeff), electron density (Rho), fat fraction, iodine concentration (IC), normalized iodine concentration (NIC), and vascular involvement. The maximum standardized uptake value (SUVmax) values were extracted from the PET/CT images. Univariate and multivariate logistic regression analyses were employed to identify independent clinicopathologic and imaging predictors of early postoperative recurrence, and a nomogram was subsequently constructed. The discrimination, calibration, and clinical utility of the nomogram were evaluated via receiver operating characteristic (ROC) curves, calibration curves, and a decision curve, respectively.ResultsComparative analysis revealed significant differences between the non-ER and ER groups in terms of the maximum tumor diameter, serum CA19-9 level, pNs, LVI, portal-venous-phase (PV-NIC) value, number of veins involved, and SUVmax (all P values <0.05). Multivariate logistic regression analysis revealed lymph node metastasis [odds ratio (OR) =19.610; 95% confidence interval (CI): 1.211–340.406; P=0.032], a low PV-NIC value (OR =0.769; 95% CI: 0.617–0.945; P=0.028), a greater number of invaded vessels (OR =8.660; 95% CI: 1.083–110.245; P=0.043), and an elevated SUVmax (OR =1.739; 95% CI: 1.091–4.142; P=0.027) as independent predictors of ER in patients with PDAC. The comprehensive model achieved an area under the curve of 0.979, along with robust calibration (calibration slope =0.91).ConclusionsThe nomogram model based on DECT parameters, the PET/CT SUVmax, and clinicopathological parameters effectively predicted early postoperative recurrence in patients with PDAC.

A preoperative risk model for early recurrence after radical resection may facilitate initial treatment decisions concerning the use of neoadjuvant therapy for patients with pancreatic ductal adenocarcinoma

BACKGROUNDPredicting early recurrence (ER), (≤ 12 months) after pancreatic ductal adenocarcinoma (PDAC) resection remains challenging. Preoperative biomarkers such as carbohydrate antigen 19-9 (CA19-9) and computed tomography (CT) lack optimal specificity and reproducibility. Extracellular volume (ECV), measured on equilibrium-phase CT to quantify stromal fibrosis, correlates with PDAC progression but its utility for ER prediction is unknown. This study evaluates preoperative CT-ECV as a novel biomarker to predict ER following curative-intent PDAC resection.AIMTo investigate the utility of CT-ECV for preoperative prediction of ER in PDAC patients after R0 resection.METHODSThis retrospective study included 93 PDAC patients undergoing R0 resection and preoperative pancreatic CT from January 2020 to November 2023. Clinical and CT features were analyzed. ECV was calculated using unenhanced and equilibrium-phase CT. Univariable and multivariable Cox regression identified ER predictors, followed by receiver operating characteristic analysis. Recurrence-free survival (RFS) was assessed by the Kaplan-Meier method.RESULTSMultivariable analysis identified elevated CT-ECV [hazard ratio (HR) = 1.05; 95% confidence interval (CI): 1.02-1.09; P = 0.003], high preoperative CA19-9 (HR = 1.00; 95%CI: 1.00-1.00; P = 0.002), and poor tumor grade (HR = 2.51; 95%CI: 1.20-5.22; P = 0.014) as independent ER predictors. CT-ECV demonstrated comparable predictive accuracy to tumor grade [areas under the curve (AUC): 0.736 vs 0.650; P = 0.202]. Combining CT-ECV and CA19-9 achieved a higher AUC than tumor grade alone (0.759 vs 0.650; P < 0.05). Kaplan-Meier analysis revealed significantly shorter RFS in patients with low CT-ECV (≤ 35.37%), elevated CA19-9 (> 55 U/mL), or poorly differentiated tumors compared to those with high CT-ECV (> 35.37%), low CA19-9 (≤ 55 U/mL), or moderately/well-differentiated tumors.CONCLUSIONCT-derived ECV is a promising non-invasive biomarker for preoperative ER prediction in PDAC. Combined with CA19-9, it outperforms tumor grade in stratifying recurrence risk, offering a clinically actionable tool for optimizing postoperative management.

Objectives Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate post-curative surgery. This study aimed to evaluate the combined predictive value of preoperative carbohydrate antigen 19-9 (CA19-9) and neutrophil-to-lymphocyte ratio (NLR) for early recurrence in resected PDAC patients. Methods This was a single-centre retrospective study involving 151 patients diagnosed with PDAC. Data on patient demographics, clinical characteristics and preoperative haematological parameters were collected. Early recurrence was defined as recurrence within the first 12 months after surgery. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with early recurrence. Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) analyses were used to assess the diagnostic performance of CA19-9, NLR and their combination. Results Among 151 patients (median follow-up: 21 months), 32.45% (n = 49) experienced early recurrence. Multivariate logistic regression analysis revealed that preoperative CA19-9 levels and NLR were independently associated with early recurrence. ROC curve analysis demonstrated that the combination of NLR and CA19-9 had significantly better performance in predicting early recurrence compared to NLR or CA19-9 alone. Conclusion The combination of preoperative CA19-9 and NLR enhances predictive accuracy for early recurrence in PDAC, offering a useful tool for postoperative risk stratification.

Initial pancreatic ductal adenocarcinoma tumor resectability status is associated with early distant recurrence after neoadjuvant therapy followed by resection

Pancreatic ductal adenocarcinoma (PDAC) is a disease with a very unfavorable prognosis. Surgical resection represents the only potentially curative treatment option, but recurrence after complete resection is almost certain. In an exploratory attempt we here aimed at identifying preoperative plasma protein biomarkers with the potential to predict early recurrence after resection of PDAC. Peripheral blood samples from 14 PDAC patients divided into three groups according to their time to tumor recurrence after curatively intended resection (early: < 6 months, medium: 6–12 months, late: > 12 months) underwent targeted proteome analysis. Proteins most strongly discriminating early and late recurrence were then examined in a number of established PDAC cell lines and their culture supernatants. Finally, PDAC organoid lines from primary tumors of patients with early and late recurrence were analyzed for confirmation and validation of results. In total, 23 proteins showed differential abundance in perioperative plasma from PDAC patients with early recurrence when compared to patients with late recurrence. Following confirmation of expression on a transcriptional and translational level in PDAC cell lines we further focused on three upregulated (MAEA, NT5E, AZU1) and two downregulated proteins (ATP6AP2, MICA). Increased expression of NT5E was confirmed in a subset of PDAC organoid cultures from tumors with early recurrence. MICA expression was heterogeneous and ATP6AP2 levels were very similar in both organoids from early and late recurrent tumors. Most strikingly, we observed high MAEA expression in all tested PDAC (n = 7) compared to a non-cancer ductal organoid line. MAEA also demonstrated potential to discriminate early recurrence from late recurrence PDAC organoids. Our study suggests that identification of plasma protein biomarkers released by tumor cells may be feasible and of value to predict the clinical course of patients. Prediction of recurrence dynamics would help to stratify up-front resectable PDAC patients for neoadjuvant chemotherapy approaches in an individualized fashion. Here, MAEA and NT5E were the most promising candidates for further evaluation.

BackgroundMinimally invasive diagnostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are warranted to facilitate accurate diagnosis. This study identified diagnostic plasma proteins based on proteomics of tumor secretome.Materials and MethodsSecretome of tumor and normal tissue was collected after resection of PDAC and dCCA. Differentially expressed proteins were measured by mass spectrometry. Selected candidate biomarkers and carbohydrate antigen 19‐9 (CA19‐9) were validated by enzyme‐linked immunosorbent assay in plasma from patients with PDAC (n = 82), dCCA (n = 29), benign disease (BD; n = 30), and healthy donors (HDs; n = 50). Areas under the curve (AUCs) of receiver operator characteristic curves were calculated to determine the discriminative power.ResultsIn tumor secretome, 696 discriminatory proteins were identified, including 21 candidate biomarkers. Thrombospondin‐2 (THBS2) emerged as promising biomarker. Abundance of THBS2 in plasma from patients with cancer was significantly higher compared to HDs (p < .001, AUC = 0.844). Combined expression of THBS2 and CA19‐9 yielded the optimal discriminatory capacity (AUC = 0.952), similarly for early‐ and late‐stage disease (AUC = 0.971 and AUC = 0.911). Remarkably, this combination demonstrated a power similar to CA19‐9 to discriminate cancer from BD (AUC = 0.764), and THBS2 provided an additive value in patients with high expression levels of bilirubin.ConclusionOur proteome approach identified a promising set of candidate biomarkers. The combined plasma expression of THBS2/CA19‐9 is able to accurately distinguish patients with PDAC or dCCA from HD and BD.Implications for PracticeThe combined plasma expression of thrombospondin‐2 and carbohydrate antigen 19‐9 is able to accurately diagnose patients with pancreatic cancer and distal cholangiocarcinoma. This will facilitate minimally invasive diagnosis for these patients by distinguishing them from healthy individuals and benign diseases.

Pancreatic cancer is a highly aggressive malignancy that is characterized by early metastasis, high recurrence, and therapy resistance. Early recurrence after surgery is one of the important reasons affecting the prognosis of pancreatic cancer. This study aimed to establish an accurate preoperative nomogram model for predicting early recurrence (ER) for resectable pancreatic adenocarcinoma. We retrospectively analyzed patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2011 and December 2020. The training set consisted of 604 patients, while the validation set included 222 patients. Survival was estimated using Kaplan–Meier curves. The factors influencing early recurrence of resectable pancreatic cancer after surgery were investigated, then the predictive model for early recurrence was established, and subsequently the predictive model was validated based on the data of the validation group. The preoperative risk factors for ER included a Charlson age-comorbidity index ≥ 4 (odds ratio [OR]: 0.628), tumor size > 3.0 cm on computed tomography (OR: 0.628), presence of clinical symptoms (OR: 0.515), carbohydrate antigen 19-9 > 181.3 U/mL (OR 0.396), and carcinoembryonic antigen > 6.01 (OR: 0.440). The area under the curve (AUC) of the predictive model in the training group was 0.711 (95% confidence interval: 0.669–0.752), while it reached 0.730 (95% CI: 0.663–0.797) in the validation group. The predictive model may enable the prediction of the risk of postoperative ER in patients with resectable pancreatic ductal adenocarcinoma, thereby optimizing preoperative decision-making for effective treatment.

Gene Variants That Affect Levels of Circulating Tumor Markers Increase Identification of Patients With Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) often recurs early after radical resection, and such early recurrence (ER) is associated with a poor prognosis. Predicting ER is useful for determining the optimal treatment. One hundred fifty-three patients who underwent pancreatectomy for PDAC were divided into an ER group (n = 54) and non-ER group (n = 99). Clinicopathological factors were compared between the groups, and the predictors of ER and prognosis after PDAC resection were examined. The ER group had a higher platelet count, higher platelet-to-lymphocyte ratio (PLR), higher preoperative CA19-9 concentration, higher SPan-1 concentration, larger tumor diameter, and more lymph node metastasis. The receiver operating characteristic (ROC) curve analysis identified cut-off values for PLR, carbohydrate antigen 19-9 (CA19-9), SPan-1, and tumor diameter. In the multivariate analysis, a high PLR, high CA19-9, and tumor diameter of >3.1 cm were independent predictors of ER after resection (all p < 0.05). When the parameter exceeded the cut-off level, 1 point was given, and the total score of the three factors was defined as the ER prediction score. Next, our new ER prediction model using PLR, CA19-9 and tumor diameter (Logit(p) = 1.6 + 1.2 × high PLR + 0.7 × high CA19-9 + 0.5 × tumor diameter > 3.1cm) distinguished ER with an area under the curve of 0.763, a sensitivity of 85.2%, and a specificity of 55.6%. ER after resection of PDAC can be predicted by calculation of a score using the preoperative serum CA19-9 concentration, PLR, and tumor diameter.

This study aimed to identify predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma (PDAC) resection with and without neoadjuvant therapy. Included were patients who underwent PDAC resection (2014-2016). Multivariable multinomial regression was performed to identify preoperative predictors for manifestation of recurrence within 3, 6 and 12 months after PDAC resection. 836 patients with a median follow-up of 37 (interquartile range [IQR] 30-48) months and overall survival of 18 (IQR 10-32) months were analyzed. 670 patients (80%) developed recurrence: 82 patients (10%) <3 months, 96 patients (11%) within 3-6 months and 226 patients (27%) within 6-12 months. LogCA 19-9 (OR 1.25 [95% CI 1.10-1.41]; P<0.001) and neoadjuvant treatment (OR 0.09 [95% CI 0.01-0.68]; P=0.02) were associated with recurrence <3 months. LogCA 19-9 (OR 1.23 [95% CI 1.10-1.38]; P<0.001) and 0-90° venous involvement on CT imaging (OR 2.93 [95% CI 1.60-5.37]; P<0.001) were associated with recurrence within 3-6 months. A Charlson Age Comorbidity Index ≥4 (OR 1.53 [95% CI 1.09-2.16]; P=0.02) and logCA 19-9 (OR 1.24 [95% CI 1.14-1.35]; P<0.001) were related to recurrence within 6-12 months. This study demonstrates preoperative predictors that are associated with the manifestation of early and very early recurrence after PDAC resection. Knowledge of these predictors can be used to guide individualized surveillance and treatment strategies.

Several patients with pancreatic ductal adenocarcinoma (PDAC) experience postoperative early recurrence (ER). We evaluated PDAC patients to identify the risk factors for postoperative ER (≤6 months), including preoperative serum DUPAN-2 level. We retrospectively evaluated 74 PDAC patients who underwent pancreatectomy with curative intent. Clinicopathological factors including age, sex, body mass index, postoperative complications, pathological factors, preoperative C-reactive protein/albumin ratio, neutrophil/lymphocyte ratio, modified Glasgow prognostic score, preoperative tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, SPAN-1, and DUPAN-2), and history of adjuvant chemotherapy were investigated. Early recurrence risk factors were determined using multivariate logistic regression analysis. Recurrence and ER occurred in 52 (70.3%) and 23 (31.1%) patients, respectively. Univariate analysis revealed that postoperative complications, C-reactive protein/albumin ratio ≥0.02, neutrophil/lymphocyte ratio ≥3.01, carbohydrate antigen 19-9 ≥ 92.3 U/mL, SPAN-1 ≥ 69 U/mL, DUPAN-2 ≥ 200 U/mL, and absence of adjuvant chemotherapy were significant risk factors for ER. In multivariate analysis, DUPAN-2 ≥ 200 U/mL (P = 0.04) and absence of adjuvant chemotherapy (P = 0.02) were identified as independent risk factors for ER. A higher level of preoperative DUPAN-2 was an independent risk factor for ER. For patients with high DUPAN-2 level, neoadjuvant therapies might be required to avoid ER.

Background: We aimed to evaluate the use of preoperative clinicophysiological parameters as predictive risk factors for early recurrence of pancreatic ductal adenocarcinoma (PDAC) after curative resection. Methods: A total of 260 patients who underwent pancreatic resection for PDAC between 2007 and 2015 were examined retrospectively. We divided the patients into those with early recurrence (within 6 months; group A, n = 52) and those with relapse within ≥6 months or without recurrence (group B, n = 208). Data regarding clinicophysiological parameters were analyzed as predictors of disease-free survival (DFS). These factors were analyzed by χ² tests on univariate analysis and Cox proportional hazard models on multivariate analyses. Kaplan-Meier survival curves were generated using log-rank tests. Results: Groups A and B had significantly different preoperative carbohydrate antigen 19-9 (CA19-9) levels, carcinoembryonic antigen (CEA) levels, and curability. Univariate and multivariate analysis showed that CA19-9 and CEA were independent prognostic factors for early recurrence. Patients with CA19-9 levels > 124.65 U/mL had significantly shorter DFS than those with lower levels, as did patients with CEA levels > 4.45 ng/mL. Conclusions: Our results show that elevated CA19-9 (> 124.65 U/mL) and CEA (> 4.45 ng/mL) were independent predictors of early recurrence after pancreatic resection in PDAC patients.