Independent Risk Factors For Early Recurrence Research Articles

Tumor Apparent Diffusion Coefficient is Associated with Early Recurrence of Intrahepatic Cholangiocarcinoma

Rationale and ObjectivesIdentifying intrahepatic cholangiocarcinoma (iCCA) patients who are at high risk for early recurrence (ER) can guide personalized treatment strategy and improve survival. This study aimed to investigate the value of preoperative MRI, especially diffusion-weighted imaging, in predicting ER, including in patients receiving neoadjuvant therapy. Materials and methodsThis study included 175 pathologically-confirmed iCCA patients who underwent curative resection (114 men, 61 women; mean age 59.0±9.56 years). MRI features, particularly apparent diffusion coefficient (ADC), were analyzed and compared between ER and non-ER cases. Survival analyses of ER were evaluated using Cox regression and Kaplan-Meier analysis. ResultsER occurred in 54.3% (95/175) of patients. Multivariate logistic regression analysis identified tumor ADC as the only independent predictor of ER (odds ratio=0.034, P<0.001), with AUCs of 0.758 (95%CI 0.664, 0.836) in the testing cohort and 0.779 (95%CI 0.622, 0.893) in the validation cohort. The optimal ADC threshold was 1.273×10-3mm2/s. Tumor ADC was comparable to the AJCC 8th staging system in predicting ER (AUC 0.758 vs 0.650 in testing cohort and 0.779 vs 0.661 in validation cohort). Multivariate Cox analysis identified high tumor burden score (HR=1.109, P=0.009), non-smooth margin (HR=2.265, P=0.008) and tumor ADC (HR=0.111, P<0.001) as independent risk factors for ER. Lower ADC values were linked to shorter RFS in both testing and validation cohorts (P<0.001 and 0.0219), as well as in patients receiving neoadjuvant therapy (P=0.003). ConclusionPreoperative MRI, particularly ADC, can help predict ER in iCCA, regardless of the application of neoadjuvant therapy, comparable to the AJCC 8th staging system.

CEUS in prediction of early recurrence of hepatocellular carcinoma after curative resection and to stratify the risk of early recurrence: a retrospective observational study.

Early recurrence (ER) after surgery is related to early death in patients with hepatocellular carcinoma (HCC) after radical resection. To explore the role of preoperative contrast-enhanced ultrasound (CEUS) in predicting ER of HCC after curative resection and to stratify the risk of ER. This study evaluated consecutive 556 patients with HCC who were examined by CEUS during the 2weeks before curative resection between January 2011 and December 2018. ER was defined as intrahepatic and/or extrahepatic recurrence within 2year after resection of HCC. Univariate and logistic regression analyses were performed to identify independent risk factors for ER after surgical resection of HCC. Recurrence-free time (RFS) rates were analyzed and compared by log-rank test. ER occurred in 307 (55.2%) of the 556 patients. Univariate and multivariate analyses revealed that a tumor size ≥ 30mm and satellite nodules seen on CEUS, DL(deep learning) radiomics reoccurrence score based on the frame of image with the maximum intensity of CEUS and an elevated alpha-fetoprotein level were significantly associated with ER (P < .05). Based on the number of predictors present, patients with CEUS LR-5 HCC were stratified into three risk subgroups: risk group 3 (high-risk patients, 4 predictors), risk group 2 (medium-risk patients, 2-3 predictors), and risk group 1 (low-risk patients, 0-1 predictor). The 2-year RFS rate was 19.4% in risk group 3, 40.9% in risk group 2, and 48.1% in risk group 1; the corresponding mean RFS times were 14.0 ± 2.9months, 43.7 ± 6.6months, and 55.5 ± 2.8months, respectively (P < .001). Tumor size ≥ 30mm and satellite nodules seen on CEUS, DL radiomics reoccurrence score based on the frame of image with the maximum intensity of CEUS and an elevated alpha-fetoprotein level can predict ER of HCC.

O138: Predictors of early recurrence of oesophagogastric adenocarcinoma after neoadjuvant FLOT

Abstract Background Although survival of patients with oesophagogastric adenocarcinomas has improved over the years, rates of cancer recurrence remain high. There is limited research on predictors for early recurrence (ER), especially in patients receiving FLOT chemotherapy. The aim of this study was to investigate ER and survival rates and identify risk factors of ER. Methods Patients receiving neoadjuvant chemotherapy with FLOT for oesophagogastric adenocarcinoma at single high-volume centre between August 2018 and October 2022 were evaluated for early recurrence defined as disease present within 1 year of surgery. Multivariable analysis was conducted to identify risk factors for ER. Patients who died in-hospital or within 90 days of surgery and those with positive longitudinal margin were excluded. Results 169 patients were included. 92.9% and 41.4% of patients completed all four neoadjuvant and adjuvant cycles of FLOT respectively. 51 patients (30.2%) developed recurrence in the follow up period with 24 patients (14.2%) having ER. Recurrence free survival and overall survival at one year were 84.1% and 91.7% respectively. The estimated median survival after recurrence was 4.8 months. Extracapsular spread was found to be independent risk factor for ER (OR 6.507, 95% CI 1.964-21.556, p=0.002) in multivariable analyses together with ypN3 stage (OR 7.204, 95% CI 1.118-46.403, p=0.038). Conclusions The variables identified in this study may be helpful in determining patients at a higher risk of ER following curative surgery. Understanding these predictors may help tailor the follow up care of these patients, such as regular surveillance imaging, treatment, and frequency of reviews.

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

PurposeTo improve the preoperative prediction efficacy for patients with risk for early recurrence (ER) of distal cholangiocarcinoma (DCC). Methods56 patients pathologically diagnosed as DCC were included. Their clinical data and preoperative upper abdominal enhanced MSCT images were retrospectively reviewed to look for risk factors associated with ER. ER scores were calculated by Distal Cholangiocarcinoma Early Recurrence (DICER) score and optimized ER score (OERS). Chi-square test or Mann-Whitney U test was used to compare the differences between ER group and Non-ER group, DICER score and OERS, and TNM stage and OERS. Binary logistic regression analyses were performed to identify risk factors of ER. ResultsOf 56 DCC patients, 15 (26.8 %) experienced ER who were classified as ER group. Patients in ER group had significantly higher percentage of soft tissue around superior mesenteric artery (STASMA), positive lymph node, microvascular invasion and TNM stage III than those in Non-ER group, among which STASMA and positive lymph node were found to be independent risk factors for ER of DCC (All P values < 0.050). DICER score was optimized by adding STASMA and positive lymph node score to form OERS. OERS predicted more accurately than DICER score in low- and high-risk patients for ER of DCC (30.0 % vs. 0 %, 50.0 % vs. 75.0 %, P < 0.001). ConclusionsBy adding preoperative imaging indicators, OERS could improve the predictive efficacy for ER of DCC.

Development and validation of web calculators to predict early recurrence and long-term survival in patients with duodenal papilla carcinoma after pancreaticoduodenectomy

BackgroundDuodenal papilla carcinoma (DPC) is prone to relapse even after radical pancreaticoduodenectomy (PD) (including robotic, laparoscopic and open approach). This study aimed to develop web calculators to predict early recurrence (ER) (within two years after surgery) and long-term survival in patients with DPC after PD.MethodsPatients with DPC after radical PD were included. Univariate and multivariate logistic regression analyses were used to identify independent risk factors. Two web calculators were developed based on independent risk factors in the training cohort and then tested in the validation cohort.ResultsOf the 251 patients who met the inclusion criteria, 180 and 71 patients were enrolled in the training and validation cohorts, respectively. Multivariate logistic regression analysis revealed that tumor size [Odds Ratio (OR) 1.386; 95% confidence interval (CI) 1070–1.797; P = 0.014]; number of lymph node metastasis (OR 2.535; 95% CI 1.114–5.769; P = 0.027), perineural invasion (OR 3.078; 95% CI 1.147–8.257; P = 0.026), and tumor differentiation (OR 3.552; 95% CI 1.132–11.152; P = 0.030) were independent risk factors for ER. Nomogram based on the above four factors achieved good C-statistics of 0.759 and 0.729 in predicting ER in the training and the validation cohorts, respectively. Time-dependent ROC analysis (timeROC) and decision curve analysis (DCA) revealed that the nomogram provided superior diagnostic capacity and net benefit compared with single variable.ConclusionsThis study developed and validated two web calculators that can predict ER and long-term survival in patients with DPC with high degree of stability and accuracy.

Effect of multiple peritumoral regions of interest ranges based on computed tomography radiomics for the prediction of early recurrence of hepatocellular carcinoma after resection.

Early recurrence (ER) of hepatocellular carcinoma (HCC) is defined as recurrence that occurs within two years after resection. Our study aimed to determine the optimal peritumoral regions of interest (ROI) range by comparing the effect of multiple peritumoral radiomics ROIs on predicting ER of HCC, and to develop and validate a combined clinical-radiomics prediction model. A total of 160 HCC patients were randomly divided into a training cohort (n=112) and a validation cohort (n=48). The intratumoral original ROI was outlined based on enhanced computed tomography images and then used as the base to sequentially extend outward 1-5 mm to form peritumoral ROI. We developed a logistic regression model to predict ER of HCC. The efficacy of different ROI prediction models was compared to determine the optimal ROI. The combined model divided the patients into a high-risk group and low-risk group. Ninety-seven (60.6%) of the patients were ER; the remaining 63 (39.4%) were not ER. The area under the curve values and 95% confidence intervals for ROI 3 were 0.867 (0.802-0.933) and 0.807 (0.682-0.931) in the training and validation cohorts, respectively, and ROI 3 was identified as the optimal ROI. Multivariate logistic regression analysis determined microvascular invasion (MVI) (P=0.037) and alpha-fetoprotein (AFP) (P=0.013) to be independent risk factors for ER. The combined clinical-radiomic model containing the radiomics score, MVI, and AFP had the optimal predictive efficacy, with area under the curve values and 95% confidence intervals of 0.903 (0.848-0.957) and 0.830 (0.709-0.952) in the training and validation cohort, respectively. Subgroup analysis showed significantly ER predicted in the high-risk group than the low-risk group (P<0.001). Peritumoral radiomics 3 mm range was determined as the optimal ROI in this study. The clinical-radiomics combined models can effectively stratify high- and low-risk patients for timely clinical treatment and decision making.

Abstract 2206: Machine learning radiomics to predict early recurrence of intrahepatic cholangiocarcinoma after curative resection: a multicenter cohort study

Abstract Background and Aims: The prognosis of intrahepatic cholangiocarcinoma (ICC) is dismal because of a high incidence of postoperative recurrence. Identifying patients who are likely to experience recurrence is important. We aim to construct radiomics models by machine learning algorithms to predict early recurrence (ER) of ICC after curative resection. Methods: Patients with ICC undergoing curative resection from three institutions were retrospectively recruited and assigned to training and external validation cohorts. Clinical data, contrast-enhanced computed tomography (CECT) images and follow-up information were collected. MRIcroGL and python software were used to segment and extract radiomics features, and student's t-test and mRMR algorithm were performed to further screen features. Logistic regression analysis was used to identify risk factors of ER. Various machine learning algorithms were used to construct predictive models. Predictive performances were evaluated by the receiver operating characteristic (ROC) curves, calibration curves and decision curves analysis (DCA) curves in the external validation cohort. Results: A total of 127 patients with ICC undergoing curative liver resection were enrolled, including 90 patients in the training set and 37 patients in the validation set. Seventy-one (55.9%) patients exhibited ER within one year after surgery, who experienced worse overall survival (OS) than patients with late recurrence and without recurrence (p&amp;lt;0.001).Male gender, vascular invasion, TNM stage III-IV and elevated CA19-9 were independent risk factors of ER, and the resulting clinical model had an AUC value of 0.685.A total of 57 differential radiomics features were identified from pre-treatment CECT images and the 10 most important features were utilized for subsequent modeling. Seven machine learning radiomics models were developed to predict ER of ICC,with the mean AUC value of 0.87±0.02.Among various machine learning algorithms, Random Forest, Neural Network and Support Vector Machine achieved the highest AUCs of 0.89.Additionally, we incorporated clinical data to build seven clinical-radiomics models, of which the Neural Network model had highest AUC value of 0.93.The calibration and DCA curves also indicated that machine learning radiomics models and clinical-radiomics models performed much better than the clinical model. Conclusions: We construct valuable machine learning radiomics models derived from preoperative CECT to predict postoperative ER of ICC, which may serve as an novel non-invasive tool for clinicians to determine surveillance strategies and optimize individual management. Citation Format: Zhiyuan Bo, Bo Chen, Yi Yang, Zhengxiao Zhao, Yi Wang, Gang Chen. Machine learning radiomics to predict early recurrence of intrahepatic cholangiocarcinoma after curative resection: a multicenter cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2206.

DUPAN-2 as a Risk Factor of Early Recurrence After Curative Pancreatectomy for Patients With Pancreatic Ductal Adenocarcinoma.

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.

Preoperative prediction of early recurrence of HBV-related hepatocellular carcinoma (≤5 cm) by visceral adipose tissue index.

This study aimed to investigate whether visceral adipose tissue index (VATI) is a significant risk factor for the early recurrence (ER) of HBV-related hepatocellular carcinoma (HCC) (≤5 cm) after hepatectomy. The recruited cohort patients who were positive for hepatitis B virus, presented with surgically confirmed HCC (≤5 cm) from Army Medical University (internal training cohort: n = 192) and Chongqing Medical University (external validation group: n = 46). We measured VATI, subcutaneous adipose tissue index (SATI) via computed tomography (CT). ER was defined as recurrence within 2 years after hepatectomy. The impact of parameters on outcome after hepatectomy for HCC was analyzed. Univariate analysis showed that alpha-fetoprotein levels (p = 0.044), body mass index (BMI) (p < 0.001), SATI (p < 0.001), and VATI (p < 0.001) were significantly different between ER and non-ER groups in internal training cohort. Multivariate analysis identified VATI as an independent risk factor for ER (odds ratio = 1.07, 95% confidence interval: 1.047-1.094, p < 0.001), with a AUC of 0.802, based on the cut-off value of VATI, which was divided into high risk (≥37.45 cm2/m2) and low risk (<37.45 cm2/m2) groups. The prognosis of low risk group was significantly higher than that of high risk group (p < 0.001). The AUC value of VATI in external validation group was 0.854. VATI was an independent risk factor for the ER, and higher VATI was closely related to poor outcomes after hepatectomy for HBV-related HCC (≤5 cm).

Efficacy and Safety of Sustained-Release Metoprolol With Dronedarone After Radiofrequency Ablation of Paroxysmal Atrial Fibrillation: A Propensity Matched Analysis

The high early recurrence (ER) rate after radiofrequency catheter ablation (RFCA) seriously affects the prognosis of patients with atrial fibrillation (AF), and there are still controversies regarding the best preventive drugs for postoperative recurrence. A single-center retrospective study was conducted on patients with paroxysmal atrial fibrillation (PAF) who received metoprolol sustained-release tablets combined with dronedarone (observation group) and dronedarone alone (control group) after the first RFCA. A matching cohort was established using a 1:1 propensity score matching method to compare the incidence of ER, cardiac function, inflammation level, quality of life (QoL), and antiarrhythmic drugs (AADs)-related adverse reactions between groups. A total of 56 pairs of patients were successfully matched. The incidence of ER in the observation group was significantly lower than that in the control group (32% vs 14%, p=0.033); the left atrial diameter in the observation group was significantly lower than that in the control group on Day 90 after RFCA (38 ±4 vs 40 ± 5, p=0.021), and the QoL of the observation group was significantly improved on the thirtieth and ninetieth days after RFCA compared with the control group (72 ± 5 vs 69 ± 9, p=0.031; 73 ± 4 vs 70 ± 9, p=0.025). Multifactorial Cox analysis showed that diabetes mellitus, left atrial diameter >45 mm, ventricular rate >110 beats/min, and postoperative AADs were independent risk factors for ER in patients with PAF. The incidence of sinus bradycardia in the observation group was significantly higher than that in the control group (18% vs 3.6%, p=0.029), but there was no statistical difference in the overall incidence of AADs-related adverse reactions between groups. Compared with dronedarone alone, dronedarone combined with metoprolol sustained-release tablets can significantly reduce ER after RFCA in patients with PAF and improve cardiac function and QoL, without increasing the AADs-related adverse reactions.

Long-term outcomes of staged liver resection for synchronous liver metastases from colorectal cancer and the clinical impact of early recurrence: A single-center retrospective cohort study.

This study was undertaken to evaluate the long-term outcomes of staged liver resection for synchronous liver metastases (SLM) from colorectal cancer (CRC), and to elucidate the prognostic impact and predictors of early recurrence (ER), which was defined as recurrence within 6 mo. Patients with SLM from CRC, except for initially unresectable SLM, from January 2013 to December 2020 were included. First, overall survival (OS) and relapse-free survival (RFS) after staged liver resection were evaluated. Second, eligible patients were classified as follows: patients who were unresectable after resection of CRC (UR), patients with ER, and patients without ER (non-ER), and their OS after resection of CRC were compared. In addition, risk factors for ER were identified. The 3-y OS and RFS rates after resection of SLM were 78.8% and 30.8%, respectively. Next, the eligible patients were classified as follows: ER (N=24), non-ER (N=56), and UR (N=24). The non-ER group had a significantly better OS than the ER (3-y OS: 89.7% vs 48.0%, P=.001) and UR (3-y OS: 89.7% vs 61.6%, P < .001) groups, while there was no significant difference between the ER and UR groups in OS (3-y OS: 48.0% vs 61.6%, P=.638). Increasing carcinoembryonic antigen (CEA) before and after resection of CRC was identified as an independent risk factor for ER. Staged liver resection for SLM from CRC was feasible and useful for oncological evaluation, as changes in CEA could predict ER, which was associated with a poor prognosis.

A novel online calculator to predict early recurrence and long-term survival of patients with resectable pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: A multicenter study

BackgroundPancreatic ductal adenocarcinoma (PDAC) is prone to relapse even after radical pancreaticoduodenectomy (PD) (including robotic, laparoscopic and open approach). This study aimed to develop an online nomogram calculator to predict early recurrence (ER) (within one year after surgery) and long-term survival in patients with PDAC. MethodsPatients with PDAC after radical PD were included. Univariate and multivariate logistic regression analysis was used to identify independent risk factors. An online nomogram calculator was developed based on independent risk factors in the training cohort and then tested in the internal and external validation cohorts. ResultsOf the 569 patients who met the inclusion criteria, 310, 155, and 104 patients were in the training, internal and external validation cohorts, respectively. Multivariate analysis revealed that preoperative carbohydrate antigen19-9 (CA19-9) [Odds Ratio (OR) 1.002; 95% confidence interval (CI) 1.001–1.003; P = 0.001], fibrinogen/albumin (FAR) (OR 1.132; 95% CI 1.012–1.266; P = 0.029), N stage (OR 2.291; 95% CI 1.283–4.092; P = 0.005), and tumor differentiation (OR 3.321; 95% CI 1.278–8.631; P = 0.014) were independent risk factors for ER. Nomogram based on the above four factors achieved good C-statistics of 0.772, 0.767 and 0.765 in predicting ER in the training, internal and external validation cohorts, respectively. Time-dependent ROC analysis (timeROC) and decision curve analysis (DCA) revealed that the nomogram provided superior diagnostic capacity and net benefit compared with other staging systems. ConclusionThis multi-center study developed and validated an online nomogram calculator that can predict ER and long-term survival in patients with PDAC with high degrees of stability and accuracy.

Multiparametric liver MRI for predicting early recurrence of hepatocellular carcinoma after microwave ablation

BackgroundHigh early recurrence (ER) of hepatocellular carcinoma (HCC) after microwave ablation (MWA) represents a sign of aggressive behavior and severely worsens prognosis. The aim of this study was to estimate the outcome of HCC following MWA and develop a response algorithmic strategy based on multiparametric MRI and clinical variables.MethodsIn this retrospective study, we reviewed the records of 339 patients (mean age, 62 ± 12 years; 106 men) treated with percutaneous MWA for HCC between January 2014 and December 2017 that were evaluated by multiparametric MRI. These patients were randomly split into a development and an internal validation group (3:1). Logistic regression analysis was used to screen imaging features. Multivariate Cox regression analysis was then performed to determine predictors of ER (within 2 years) of MWA. The response algorithmic strategy to predict ER was developed and validated using these data sets. ER rates were also evaluated by Kaplan–Meier analysis.ResultsBased on logistic regression analyses, we established an image response algorithm integrating ill-defined margins, lack of capsule enhancement, pre-ablative ADC, ΔADC, and EADC to calculate recurrence scores and define the risk of ER. In a multivariate Cox regression model, the independent risk factors of ER (p < 0.05) were minimal ablative margin (MAM) (HR 0.57; 95% CI 0.35 – 0.95; p < 0.001), the recurrence score (HR: 9.25; 95% CI 4.25 – 16.56; p = 0.021), and tumor size (HR 6.21; 95% CI 1.25 – 10.82; p = 0.014). Combining MAM and tumor size, the recurrence score calculated by the response algorithmic strategy provided predictive accuracy of 93.5%, with sensitivity of 92.3% and specificity of 83.1%. Kaplan–Meier estimates of the rates of ER in the low-risk and high-risk groups were 6.8% (95% CI 4.0 – 9.6) and 30.5% (95% CI 23.6 – 37.4), respectively.ConclusionA response algorithmic strategy based on multiparametric MRI and clinical variables was useful for predicting the ER of HCC after MWA.

Early Recurrence in Resected Gallbladder Carcinoma: Clinical Impact and Its Preoperative Predictive Score.

Surgical resection is the only potentially curative therapy for gallbladder carcinoma (GBC). However, the postoperative recurrence rate is high (approximately 50%), and recurrence occasionally develops early after surgery. A total of 139 patients who underwent macroscopically curative resection for GBC between 2002 and 2018 were retrospectively reviewed. Early recurrence (ER) was defined as recurrence within 6 months after surgery. Univariate and multivariate logistic regression analysis was performed using preoperative factors that may influence early recurrence, namely patient background factors, tumor markers, imaging findings, and body composition parameters obtained preoperatively, to create a predictive score for ER. The median follow-up period was 21.9 months (range, 6.2-195.7months). Postoperative recurrence was observed in 55 (39.6%) patients, of whom 14 (25.5%) developed ER. The median overall survival after surgery was 104.7 months for the non-ER group and 15.7 months for the ER group. On multivariate analysis, high carbohydrate antigen 19-9, low muscle attenuation, high visceral fat attenuation, liver invasion, and other organ invasion on preoperative computed tomography were identified as independent risk factors for ER. A preoperatively predictive scoring system for ER was constructed by weighting the above five factors. The nomogram showed an area under the curve of 0.881, indicating good predictive potential for ER. ER in resected GBC indicates a very poor prognosis. The present preoperative scoring system can sufficiently predict ER and may be helpful in determining the optimal treatment strategies.

Tumor Stage-Based Gross Tumor Volume of Resectable Esophageal Squamous Cell Carcinoma Measured on CT: Association With Early Recurrence After Esophagectomy.

ObjectiveTo investigate relationship of tumor stage-based gross tumor volume (GTV) of esophageal squamous cell carcinoma (ESCC) measured on computed tomography (CT) with early recurrence (ER) after esophagectomy.Materials and MethodsTwo hundred and four consecutive patients with resectable ESCC including 159 patients enrolled in the training cohort (TC) and 45 patients in validation cohort (VC) underwent contrast-enhanced CT less than 2 weeks before esophagectomy. GTV was retrospectively measured by multiplying sums of all tumor areas by section thickness. For the TC, univariate and multivariate analyses were performed to determine factors associated with ER. Mann-Whitney U test was conducted to compare GTV in patients with and without ER. Receiver operating characteristic (ROC) analysis was performed to determine if tumor stage-based GTV could predict ER. For the VC, unweighted Cohen’s Kappa tests were used to evaluate the performances of the previous ROC predictive models.ResultsER occurred in 63 of 159 patients (39.6%) in the TC. According to the univariate analysis, histologic differentiation, cT stage, cN stage, and GTV were associated with ER after esophagectomy (all P-values < 0.05). Multivariate analysis revealed that cT stage and GTV were independent risk factors with hazard ratios of 3.382 [95% confidence interval (CI): 1.533–7.459] and 1.222 (95% CI: 1.125–1.327), respectively (all P-values < 0.05). Mann-Whitney U tests showed that GTV could help differentiate between ESCC with and without ER in stages cT1-4a, cT2, and cT3 (all P-values < 0.001), and the ROC analysis demonstrated the corresponding cutoffs of 13.31, 17.22, and 17.83 cm3 with areas under the curve of more than 0.8, respectively. In the VC, the Kappa tests validated that the ROC predictive models had good performances for differentiating between ESCC with and without ER in stages cT1-4a, cT2, and cT3 with Cohen k of 0.696 (95% CI, 0.498–0.894), 0.733 (95% CI, 0.386–1.080), and 0.862 (95% CI, 0.603–1.121), respectively.ConclusionGTV and cT stage can be independent risk factors of ER in ESCC after esophagectomy, and tumor stage-based GTV measured on CT can help predict ER.

Effectiveness of the Albumin-bilirubin Score as a Prognostic Factor for Early Recurrence after Curative Hepatic Resection for Hepatocellular Carcinoma

Introduction: The albumin-bilirubin (ALBI) score has been validated as a predictor of disease-free survival and overall survival in hepatocellular carcinoma (HCC). The purpose of this study was to assess the ALBI score as a risk factor for early recurrence (ER) after curative liver resection in HCC. Methods: Patients who underwent liver resection with curative intent for HCC without previous treatment between January 2004 and December 2014 were included in this retrospective study. The utility of the ALBI score in predicting ER and late recurrence (LR) was evaluated. Results: A total of 465 HCC patients were enrolled; multivariate analysis identified ALBI grade ≥2 (p=0.003) as a risk factor for ER, in addition to hepatitis B virus surface antigen (HBsAg)-positive status (p < 0.001), tumor size ≥3.5cm (p≤0.001), lymph-vascular invasion (p=0.001), and the presence of satellite lesions (p=0.009). In subgroup analysis for ALBI grade 1, Model for End-stage Liver Disease score >9 (p=0.046), HBsAg positive status (p=0.004), tumor size ≥3.5 cm (p < 0.001), lymph-vascular invasion (p=0.001), presence of satellite lesions (p=0.002), and poor tumor differentiation (p=0.007) were independent risk factors for ER; however, in subgroup analysis for ALBI grade 2, no significant associations with ER were found. Kaplan-Meier curve analysis showed that long-term survival in HCC with ER was significantly shorter than in patients with LR. Conclusions: The ALBI score was a preoperative risk factor for ER and may be useful in determining appropriate management according to liver function when recurrence develops.

A combination of platelet-to-lymphocyte ratio and carbohydrate antigen 19-9 predict early recurrence after resection 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.

Predictive Value of Contrast-enhanced Ultrasound for Early Recurrence of Single Lesion Hepatocellular Carcinoma After Curative Resection.

This retrospective study aimed to use preoperative and contrast-enhanced ultrasound (CEUS) factors to assess and reveal risk factors of early recurrence (ER) in patients with hepatocellular carcinoma (HCC). We enrolled 141 patients with primary HCC who had undergone surgical resection. The assessment of the CEUS scan includes (a) the maximum diameter of the lesion, (b) the tumor echogenicity of gray-scale ultrasound (US), (c) the morphology of the tumor, (d) the margin of the tumor, (e) the peripheral hypoechoic halo, (f) tumor necrosis, (g) nutritional arteries shown by tumors, (h) ultrasonography for diagnosis of cirrhosis, and (i) the timer on the US screen displayed the time elapsed from the saline flush and was used to determine time to washout. According to the degree of the phase, the washout rate is divided into four grades, namely, levels 1 to 4. ER is defined as the time between resection and recurrence within 12 months after surgery. Risk factors for ER HCC were analyzed. Predictors of ER on a univariate logistic regression analysis in CEUS are size, washout rate, morphology, center necrosis, and feeding artery appearing in the tumor. Multivariate analysis results indicated that feeding artery, microvascular invasion (MVI), and washout rate were independent risk factors for ER. The relative high risk of ER for washout rate 1, 2, 3, and 4 were 29.3%, 43.2%, 53.1%, and 71.4%, respectively. The appropriateness of hepatectomy in the treatment of single lesion HCC should be carefully considered when the washout rate was 4.

Effectiveness of the albumin-bilirubin score as a prognostic factor for early recurrence after curative hepatic resection for hepatocellular carcinoma.

Backgrounds/AimsThe albumin-bilirubin (ALBI) score has been validated as a predictor of disease-free survival and overall survival in hepatocellular carcinoma (HCC). The purpose of this study was to assess the ALBI score as a risk factor for early recurrence (ER) after curative liver resection in HCC.MethodsPatients who underwent liver resection with curative intent for HCC without previous treatment between January 2004 and December 2014 were included in this retrospective study. The utility of the ALBI score in predicting ER and late recurrence (LR) was evaluated.ResultsA total of 465 HCC patients were enrolled; multivariate analysis identified ALBI grade ≥2 (p=0.003) as a risk factor for ER, in addition to hepatitis B virus surface antigen (HBsAg)-positive status (p<0.001), tumor size ≥3.5cm (p≤0.001), lymph-vascular invasion (p=0.001), and the presence of satellite lesions (p=0.009). In subgroup analysis for ALBI grade 1, Model for End-stage Liver Disease score >9 (p=0.046), HBsAg positive status (p=0.004), tumor size ≥3.5 cm (p<0.001), lymph-vascular invasion (p=0.001), presence of satellite lesions (p=0.002), and poor tumor differentiation (p=0.007) were independent risk factors for ER; however, in subgroup analysis for ALBI grade 2, no significant associations with ER were found. Kaplan-Meier curve analysis showed that long-term survival in HCC with ER was significantly shorter than in patients with LR.ConclusionsThe ALBI score was a preoperative risk factor for ER and may be useful in determining appropriate management according to liver function when recurrence develops.

Correlation Between Postoperative Early Recurrence of Hepatocellular Carcinoma and Mesenchymal Circulating Tumor Cells in Peripheral Blood

BackgroundCirculating tumor cells (CTCs) have been actively studied for their functions in hepatocellular carcinoma (HCC) recurrence. However, the relationship between circulating tumor cells subtypes and hepatocellular carcinoma recurrence is still unclear. MethodsCTCs were collected from the peripheral blood of 62 postoperative HCC patients. The CTCs were isolated with a filtration-based method. Multiplex fluorescence in situ hybridization was used to characterize the CTCs based on mRNA expression levels of epithelial and mesenchymal markers. ResultsOf the 62 HCC patients, 26 were diagnosed with early recurrence (ER) and 36 did not experience recurrence. Comparison between the recurrence group and the non-recurrence group showed the total number of CTCs, mesenchymal CTCs, and mixed CTCs in the recurrence group was significantly higher than in the non-recurrence group. Receiver operator characteristic (ROC) curve analysis was performed to define the positive cutoff values as follows: total number of CTCs ≥ 4, mesenchymal CTCs ≥ 1, and mixed CTCs ≥ 3. Analysis showed that portal vein tumor thrombus (hazard ratio [HR] = 2.905, P = 0.023) and mesenchymal CTC positivity (HR = 3.453, P = 0.007) were independent risk factors for ER. The correlation between the presence of mesenchymal CTCs and time to recurrence was further examined, and the results showed significantly shortened postoperative disease-free survival in patients positive for mesenchymal CTCs (P < 0.001). ConclusionsHCC patients with positive peripheral mesenchymal CTCs have a more serious risk of ER, which could be a potential biomarker in HCC prognosis monitoring.