S100 Calcium-Binding Protein P Predicts Early Recurrence and Poor Survival in Distal Cholangiocarcinoma: A Proteomics Study.

Introduction: Colon cancer is the third most common cancer worldwide. The mainstay treatment for localized disease is surgical resection, often followed by adjuvant chemotherapy in stage III patients, and stage II patients with high-risk features. Unfortunately, some patients experience early local and/or distant recurrence. Besides classic anatomical/pathological tumor features, insight into the genomic determinants of early recurrence in colon cancer is lacking. Herein, we utilize a multi-omics approach to identify early-recurrence-specific features that could aid in more accurate risk stratification. Methods: We utilized the Cancer Genomic Atlas Colon Adenocarcinoma (TCGA-COAD) Database. Clinical, histopathological and genomic data were retrieved through the cBioPortal database. Our analysis was limited to patients with stage 2 or 3 (n = 390) disease based on the American Joint Committee on Cancer Code. Early recurrence (ER) was defined as disease relapse/recurrence within 12 months of sample acquisition post-surgery. Accordingly, patients were categorized into the ER and non-early recurrence (NER) groups based on a cut-off point of 12 months of disease-free survival. Results: The colon cancer ER and NER group included 45 and 345 patients, respectively. Comparable age, sex and race percentages were found between both groups. The ER group had significantly worse overall, progression-free, and disease-specific survival (HR: 0.083 95% CI: 0.031-0.220, HR: 0.035 95% CI: 0.011-0.0109, HR: 0.021 95% CI: 0.006-0.076, respectively). ER patients had a significantly higher proportion of patients with T4 and N2 disease based on the TNM staging system. ER patients had significant (P< 0.05) expression of TRIM46, TRPC4, ELOVL7, CSMD1, BCLAF1, and CD70 mutations, while tumor mutational burden was comparable between both groups (median TMB in ER vs NER: 4.2 vs 3.62, p = 0.28). Differential gene expression analysis revealed 68 genes to be upregulated in the ER group which were found to be enriched in hypoxia and interleukin-11 pathway genes. Genes upregulated in the NER group (n = 49) were enriched in interferon-alpha response and glycolysis/gluconeogenesis pathway genes. Proteomics analysis revealed significantly higher levels of EIF4E, CCNE1, SRSF1, SCD, and PECAM1 proteins in NER patients .Conclusion: Our results highlight insights into molecular and genomic features unique to colon cancer patients with early recurrence. Understanding such predictors for early recurrence will aid in risk stratification and help in determining patients who would derive the most benefit from adjuvant treatment considerations. Citation Format: Salma Al-Aomar, Hassan Abushukair, Alaa Zaitoun, Sara Zytoon, Sara Illeyyan, Husam Almomani, Ghayda'a Al-Majali, Arafat Hammad, Khaled Obeidat, Fuad Turfah, Awni Shahait, Fadwa Ali. Determinants of early recurrence in surgically-resected colon cancer: A multi-omics analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2400.

The occurrence of recurrent papillary and follicular thyroid carcinomas is not unusual. Numerous studies have reported the association between risk factors of initial surgery and recurrence of papillary and follicular thyroid carcinomas. However, we do not have sufficient data to analyze the time of postoperative recurrence associated with therapeutic results and cancer mortality. We hypothesized that an early recurrence of papillary and follicular thyroid cancers implies a rapid growth of cancer resulting in high mortality rate. We conducted a retrospective study in a medical center in northern Taiwan. The investigation included 2148 cases of papillary and follicular thyroid carcinoma, including 325 recurrent cases during the period between 1977 and 2006. The studied cases were categorized into early or late recurrence groups. Cases with an early recurrence were defined as those in which recurrence occurred in the first year following thyroid surgery. Tumor size, radioactive iodide treatment, multifocality, and tumor-node metastasis stage were independent predictors of recurrence. After a mean follow-up of 8.7 +/- 0.1 years, death due to thyroid cancer was observed to occur in 105 (32.3%) recurrent cases. Among the 325 recurrent cases, early recurrence was detected in 185 cases, and late recurrence was detected in 140 cases. Early recurrence was mostly observed in older male patients; a high mortality rate was associated with these cases. Distant metastases were observed in about 80% of the cases in the early recurrence group, whereas localized metastases in the neck region were observed in more than half the cases in the late recurrence group. The percentage of patients with a non-disease-free status and distant metastases in the early recurrence group was higher than that in the late recurrence group. The 10-year disease-specific survival rates were 52.5% and 85.1% for the early and late recurrence groups, respectively. Early recurrent papillary and follicular thyroid carcinomas are associated with high mortalities. Tumor size and multifocality deserve consideration as indicators of recurrence. Therefore, patients whose primary follicular or papillary thyroid carcinoma has features associated with early recurrence should probably receive more aggressive initial treatment.

Objective: To investigate the feasibility of contrast-enhanced computer tomography (CT) texture analysis in predicting early recurrence after transarterial chemoembolization (TACE) in patients with liver cancer. Methods: A retrospective analysis was performed for 47 patients with liver cancer confirmed by liver biopsy and digital subtraction angiography who underwent upper abdominal contrast-enhanced CT scan before TACE, and according to the presence or absence of focal recurrence within half a year, these patients were divided into early recurrence (ER) group and non-early recurrence (NER) group. The texture analysis was used to delineate tumor boundary layer by layer on the axial contrast-enhanced CT image before liver cancer surgery, and related parameters of tumor heterogeneity, including entropy, mean, non-uniformity, skewness, and kurtosis, were obtained. The independent samples t-test was used for comparison of texture parameters between the two groups. The receiver operating characteristic (ROC) curve was used for the analysis of entropy, mean, and non-uniformity, and the area under the ROC curve (ROC), optical cut-off value, sensitivity, and specificity were calculated to evaluate the efficiency of texture analysis in predicting early focal recurrence after TACE. Results: There were 20 patients in the ER group and 27 in the NER group. The ER group had a maximum major axis length of 88.2±36.3 mm and a maximum minor axis length of 41.4±21.4 mm, and the NER group had a maximum major axis length of 66.9±30.2 mm and a maximum minor axis length of 29.3±19.8 mm; the ER group had significantly higher maximum major and minor axis lengths than the NER group (t = 4.89 and 4.62, P < 0.001). The ER group had significantly higher entropy and non-uniformity values than the NER group, and there were no significant differences in skewness and kurtosis between the two groups. Entropy, non-uniformity, and mean had high efficiency in predicting early recurrence after TACE, and the optimal cut-off value of entropy was 4.135. Conclusion: Volumetric texture analysis of contrast-enhanced CT images before liver cancer surgery has a high value in predicting early recurrence after TACE.

PurposeEarly recurrence of hepatocellular carcinoma (HCC) remains a challenging issue after hepatic resection (HR) because of the associated poor prognosis. Models for tumor recurrence after liver transplantation (MoRAL) have been designed to predict tumor recurrence in HCC patients in the liver transplantation setting. This study aimed to validate the predictability of MoRAL for HCC recurrence or patient death and to evaluate the predictors of early HCC recurrence in hepatectomy patients with treatment-naïve solitary HCC.MethodsThis study included 443 patients with HCC recurrence after HR from January 2005 to December 2011. Patients were stratified into early recurrence (n = 312) and late recurrence (n = 131) groups according to the development of recurrence either within or more than 2 years after hepatectomy.ResultsThe median levels of alpha-fetoprotein and protein induced by vitamin K absence-II and the median MoRAL score were significantly higher in the early recurrence group than in the late recurrence group. Regarding pathologic characteristics, the median tumor size, prevalence of tumor grade 3 or 4, microvascular invasion, presence of tumor necrosis, and macrovascular invasion in the early recurrence group were greater than those in the late recurrence group. Multivariate analysis showed that tumor grade 3 or 4, microvascular invasion, and high preoperative MoRAL score were predisposing factors for early HCC recurrence after HR.ConclusionThe MoRAL score can be used to predict early recurrence in patients with HCC who undergo curative HR. Using this model, other treatments could be considered for patients with early recurrence predicted after HR.

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.

Durvalumab consolidation after concurrent chemoradiotherapy (CCRT) is the present standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). However, some patients experience early recurrence. This study sought risk factors for early recurrence during durvalumab consolidation. This retrospective multicenter study was conducted between September 2017 and September 2022. We categorized patients into early and non-early recurrence groups. Early recurrence was defined as recurrence within 6 months after the first dose of durvalumab. Of the 222 patients, 40 (18.0%) experienced early recurrence and 182 (82.0%) experienced non-early recurrence. The former group was younger than the latter group (P=0.02). Patients exhibiting lower-level programmed cell death-ligand 1 (PD-L1) expression were more likely to experience early recurrence (P=0.02). Stage IIIC patients tended to experience more early recurrence than stage IIIA/IIIB patients (P=0.055). Multivariate analyses revealed that older age [odds ratio (OR), 0.945; 95% confidence interval (CI): 0.902-0.991; P=0.02] and PD-L1 level ≥50% (OR, 0.303; 95% CI: 0.125-0.736; P=0.008) protected against early recurrence in NSCLC patients on durvalumab consolidation. Median overall survival was significantly longer in the non-early recurrence group than in the early recurrence group (non-evaluable vs. 11.0 months, respectively; P<0.001). Younger age and lower PD-L1 expression predicted early recurrence during durvalumab consolidation after CCRT. Careful follow-up of such patients is essential.

e15760 Background: Limited data exist on outcomes after recurrence after curative intent resection for pancreatic adenocarcinoma (PC). We analyzed the prognostic significance of time to recurrence and associated factors in patients with post-pancreatectomy recurrence. Methods: Patients with a documented recurrence were identified from a prospectively maintained database of all patients undergoing pancreatectomy for PC between 2009-2015 at Indiana University Simon Cancer Center. Patients were divided into early (≤12 mos after surgery) and late recurrence ( &gt; 12 mos after surgery) groups. Demographic (age, race, sex) and clinical (CA19-9, bilirubin, tumor location, diabetes at presentation, ECOG performance status, margin status, adjuvant radiation, and adjuvant and metastatic chemotherapy) data were obtained by manual chart abstraction and the IUSCC cancer registry. The primary outcome was survival after recurrence (SAR- time from recurrence to death). Chi-square was used for univariate analysis (except t-test for age). SAR was estimated with the Kaplan-Meier method and 95% CI. Cox proportional-hazard model was used for multivariate analysis (MVA). Results: Of 437 patients undergoing surgical resection for PC, 235 had documented recurrence. More patients had an early recurrence (ER) as compared to late recurrence (LR; 58.3% vs 41.7%). Median SAR was significantly shorter in ER vs LR patients (6.2 vs 8.6 months; HR, 0.71; 95% CI, 0.53-0.95; P = 0.02). Median age was higher in ER vs LR groups (64.7 and 64.2 years, P = 0.002). Diabetes at presentation was more common in ER vs LR group (42.3% vs 30.6%, P = 0.09). ER patients were significantly less likely to have received adjuvant chemotherapy (70.7% vs 84.7%, P = 0.02) or adjuvant radiation (17.8% vs 40%, P &lt; .001). MVA showed a trend towards longer SAR in LR vs ER group (adjusted HR = 0.75, 95% CI, 0.55-0.1.03, p = 0.08) however age, adjuvant chemotherapy, adjuvant radiation and diabetes at presentation were not significant predictors of SAR. Conclusions: Early recurrence after resection of PC is associated with poor SAR. Patients with early recurrence tend to be older, diabetic at presentation and were less likely to have received adjuvant chemotherapy or adjuvant radiation.

MicroRNA‐125b expression and intrahepatic metastasis are predictors for early recurrence after hepatocellular carcinoma resection

Treatment Planning for Resectable Pancreatic Cancer Based on Prediction of Postoperative Early Recurrence

Timing of death from tumor recurrence after curative gastrectomy for gastric cancer.

Optimized early recurrence score for distal cholangiocarcinoma: A new attempt by adding imaging indicators

Recurrence after liver resection for hepatocellular carcinoma (HCC) is a major clinical problem, and prognostic markers for recurrence are urgently required. For 390 HCC cases, segmented linear regression analysis with two segments was performed, and the interval for the early and late recurrence groups was partitioned at the crosspoint (676 days). We investigated whether gene expression in non-tumorous tissues of remnant liver from 39 hepatitis C virus-positive HCC cases may be associated with early recurrence of this disease. By microarray analysis, 21 genes were identified as candidate recurrence-associated genes. Further gene expression analysis was performed, and the localization and expression of the gene products of these candidate genes were immunohistochemically evaluated. Low expression of the GBP1 gene and high expression of the TSC22D3 gene were significantly (both P=0.04) associated with the risk of early recurrence. Through backward step-wise multivariate logistic regression analysis for the 21 candidate genes, high expression of GBP1 reduced [odds ratio (OR)=0.20; 95% confidence interval (CI) 0.06-0.73, P=0.02] and high expression of TSC22D3 increased the risk of early recurrence (OR=19.6; 95% CI 1.14-337.2; P=0.04). Immunohistochemical analysis revealed that hepatocytes showed strong membranous expression for GBP1 in the late recurrence group, but weak membranous expression for GBP1 in the early recurrence group. TSC22D3 was frequently expressed in lymphocytes and in a few hepatocytes in tissues of the early recurrence group. Our observations suggest that the combination of the high expression of the TSC22D3 gene and low expression of the GBP1 gene in the non-tumorous tissue of the remnant liver is significantly associated with early recurrence after surgical resection of HCC.

To determine an optimal cut-off value for distinguishing early and late recurrence in patients with laryngeal cancer after initial surgery and to evaluate the risk factors for early recurrence. This retrospective study included 328 patients with laryngeal cancer who underwent initial resection in our hospital from January 2014 to April 2018. A minimum P-value approach was used to determine the optimal cut-off value to divide patients into early and late recurrence groups. The clinicopathological characteristics were compared between the two groups. The risk factors for early recurrence were evaluated using logistic regression analysis. The optimal cut-off value to identify between early recurrence (n = 51, 50.5%) and late recurrence (n = 50, 49.5%) was 17 months (p < 1e−17). The overall survival of the late recurrence group (48.36 ± 16.02 months) was longer than the early recurrence group (32.61 ± 19.65 months) significantly (p < 0.001). Lymphovascular invasion (p = 0.038), patients without adjuvant radiotherapy (p = 0.043), advanced tumor, node, metastasis (TNM) stage (p = 0.035), and positive surgical margins (p = 0.045) were independent risk factors for early recurrence. The best cut-off value to identify early recurrence after initial surgery for laryngeal cancer was 17 months. Intensive follow-up and adjuvant radiotherapy may be beneficial for patients with risk factors for early recurrence.

Purpose: Although many studies have focused on clinical risk factors for prognosis of patients with surgically treated gastric cancer, little information is available regarding the timing of recurrent malignant disease. The purpose of this study was to determine the factors that are predictive of early and late recurrences after gastrectomy. Patients and Methods: We reviewed the hospital records of patients with hisotological proof of gastric cancer who were admitted to Sendai National Hospital during the period from 1985 to 1995. A total of 923 records were examined, and 251 patients with recurrent disease were identified. The patients were divided into an "early recurrence group" consisting of 195 patients (died within one year after surgery) and a "late recurrence group" of 56 patients (died two years or more after surgery). Clinicopathological characteristics were examined, and independent risk factors influencing the timing of recurrence were determined by a multiple logistic regression analysis. Results: The mean tumor size of early recurrence cases was larger than that of late recurrence cases (p=0.0294). Tumors penetrating the serosa with direct invasion to continuous structures were found more frequently in the early recurrence group than in the late recurrence group. The patients with early recurrence showed a higher tendency to have nodal involvement, lymphatic invasion and vascular invasion. The relative risks of early and late recurrences associated with different variables were estimated by a multiple logistic regression method. The following variables were found to be significant risk factors for early recurrence: male gender (p=0.0382), lymph node metastasis (p=0.0016), and vascular invasion (p=0.0006).Conclusion: Male patients who have node-positive gastric cancer with vascular invasion have a high risk of early recurrence.

Predictors of Recurrence After Pancreaticoduodenectomy in Ampullary Cancer: Comparison Between Non-, Early and Late Recurrence