Postoperative Recurrence-free Survival Research Articles

Genome-wide microRNA Analysis Identified miR-210-3p Over-expression in Pancreatic Cancer Tissues as a Predictor of their Local Invasiveness.

The severe malignancy of pancreatic ductal adenocarcinoma (PDAC) is mainly due to frequent local invasiveness and distant metastasis. As for local invasiveness, we previously reported that cancer-specific molecular alterations detected on resected PDAC specimen surfaces, so-called molecular surgical margin (MSM) positiveness, were significantly associated with postoperative locoregional recurrence and distant metastasis. However, due to anatomical limitations, achieving adequate surgical margins during pancreatic cancer resection is often challenging. Therefore, predicting local invasiveness based on the primary tumor's gene profile is crucial to avoid positive MSM. Genome-wide miRNA expression profiles were examined and compared between MSM-positive and negative cases. Candidate miRNAs were evaluated in another validation cohort, and their clinicopathological characteristics were examined. Mimic or inhibitor constructs of the candidate miRNA were transfected to PDAC cell lines to evaluate the miRNA function in the pancreatic cancer cell lines and detect the downstream targets. Among some candidates with highly expressed miRNAs in MSM-positive cases by miRNA expression array, recurrence-free survival (RFS) was significantly shorter in the miR-210-3p high expression group (p=0.015). High miR-210-3p was significantly associated with large tumor diameter (p=0.001), anterior invasion positive (p=0.010), and positive lymph node metastasis (p<0.001). miR-210-3p inhibition in PDAC cell lines resulted in decreased proliferation and invasiveness. The iron-sulfur cluster assembly enzyme (ISCU) gene was identified as a target of miR-210-3p. ISCU reduction was significantly observed in PDAC primary tumors with high levels of miR-210-3p, leading to mitochondrial dysfunction in miR-210-3p-overexpressing PDAC cell lines, as demonstrated by glycolysis stress tests. Highly expressed hypoxia-inducible miR-210-3p in primary PDAC tissues induces locally invasive characteristics through mitochondrial dysfunction by suppressing ISCU expression, which may result in poor postoperative RFS outcomes.

The Weight of Nutrition on Post-Resection Oncologic Morbidity and Mortality: A Systematic Review and Meta-Analysis of Nutritional Indices

Abstract Context Nutritional status is a critical factor in the selection of patients for solid tumor resection. A variety of indices have been developed to quantify nutritional status, and they have differing degrees of predictive power for various postoperative outcomes. Objective This study aimed to comprehensively evaluate the predictive ability of commonly used nutritional indices in relation to postoperative complications (POCs), recurrence-free survival (RFS), and OS. Data Sources We performed a systematic review of 14 established nutritional indices from January 2015 to July 2022: Data Extraction The primary end point was OS, while the secondary end points were POCs and RFS. A subsequent meta-analysis was performed to further assess the predictive ability of these indices for OS based on general index type, primary tumor site, and the patient’s index status. Data Analysis In this evaluation, 38 articles reporting data on 23 970 patients were analyzed, focusing on 14 nutritional indices. The indices were categorized into phenotypic, metabolic, immunologic, and combined types. Patients within the cut-off range of any index were predicted to have lower OS (hazard ratio [HR] 2.14, 95% CI 1.84–2.49, P &amp;lt; .01). Lower gastrointestinal (GI) and “other” sites were less predictive than upper GI primary tumors (HR 1.63, HR 1.82, and HR 2.54, respectively; all with P &amp;lt; .01). Phenotypic indices were less predictive than combined indices (HR 1.73 vs HR 2.47, P &amp;lt; .01). Within the combined category, there was no significant difference in the predictive ability of Prognostic Nutritional Index (PNI) vs Geriatric Nutritional Risk Index (GNRI) vs Controlling Nutritional Index (CONUT) (HR 2.63 vs HR 2.42 vs HR 2.07, P = .07). Conclusion The predictive efficacy of a nutritional index was found to be highly dependent on the index type, the primary tumor site, and the outcome of interest. In the context of upper GI resections, nutritional status appeared to be more of a significant predictor of OS, compared with cases involving lower GI and hepatic malignancies. Indices that integrate phenotypic, metabolic, and immunologic patient factors potentially offer greater clinical utility in forecasting OS.

539. ASSOCIATION BETWEEN WAITING PERIOD FOR RADICAL SURGERY AND POSTOPERATIVE RELAPSE IN CLINICAL STAGE I ESOPHAGEAL CANCER

Abstract Background Esophagectomy with locolegional lymphanedectomy based on potential lymph node metastatic risk is the current standard treatment for clinical Stage I thoracic esophageal cancer. Local excision by endoscopic submucosal dissection (ESD) is the standard treatment for clinical Stage 0, however surgery is considered as an additional treatment for pathological T1b cases due to potential metastatic risk. Cases of additional resection after ESD are those pathologically demonstrated to have a high risk of metastasis based on tumor depth and vascular invasion, etc. Compared to cases of surgery for clinical Stage I, many of these cases have a high risk of metastasis, and therefore a poor prognosis is generally expected. Addionally, the prolonged waiting time between initial diagnosis and radical surgery due to ESD may be a factor in poor prognosis, but there is currently no consensus on the risk. Therefore, we conducted a study to clarify the effect of waiting period before surgery (WP) on the risk of recurrence in clinical Stage I esophageal cancer surgery. Methods We retrospectively evaluated the association between WP and 3-year postoperative recurrence-free survival (3y-RFS) in 65 patients who underwent primary esophagectomy and gastric tube reconstruction for clinical Stage I esophageal cancer and 22 patients who underwent additional resection after ESD at our hospital. Results The WP of 87 patients was 2.12 ± 1.43 months (mean± SD), and 13 patients had postoperative recurrence (3y-RFS 85.1%). A 2-arm comparison of short or long WP with a cutoff value of 2.83 months (mean+0.5 SD) showed no clear association with 3y-RFS (100% vs 81.4%, p=0.071). A strong correlation was shown between WP and ESD (r=0.647, p&amp;lt;0.01). WP was 1.69±1.20 months (mean± SD) in 65 patients who underwent surgery as initial treatment, and 12 patients had postoperative recurrence (3y-RFS 81.5%). A 2-arm comparison of short or long WP with a cutoff value of 2.29 months (mean+0.5 SD) suggested an association with 3y-RFS (85.7% vs 55.6%, p=0.018). Conclusion Although this is a single-center, retrospective study of a small number of cases and only a univariate study due to the small number of events, it suggests that a longer waiting period before surgery may be a risk factor for postoperative recurrence.

Transmembrane serine protease 4 expression in the prognosis of radical resection for biliary tract cancer.

Recent advancements in biliary tract cancer (BTC) treatment have expanded beyond surgery to include adjuvant therapy, yet the prognosis remains poor. Identifying prognostic biomarkers could enhance the assessment of patients who have undergone radical resection for BTC. To determine transmembrane serine protease 4 (TMPRSS4) utility as a prognostic biomarker of radical resection for BTC. Medical records of patients who underwent radical resection for BTC, excluding intrahepatic cholangiocarcinoma, were retrospectively reviewed. The associations between TMPRSS4 expression and clinicopathological factors, overall survival, and recurrence-free survival were analyzed. Among the 85 patients undergoing radical resection for BTC, 46 (54%) were TMPRSS4-positive. The TMPRSS4-positive group exhibited significantly higher preoperative carbohydrate antigen 19-9 (CA19-9) values and greater lymphatic invasion than the TMPRSS4-negative group (P = 0.019 and 0.039, respectively). Postoperative overall survival and recurrence-free survival were significantly worse in the TMPRSS4-positive group (median survival time: 25.3 months vs not reached, P < 0.001; median survival time: 28.7 months vs not reached, P = 0.043, respectively). Multivariate overall survival analysis indicated TMPRSS4 positivity, pT3/T4, and resection status R1 were independently associated with poor prognosis (P = 0.032, 0.035 and 0.030, respectively). TMPRSS4 positivity correlated with preoperative CA19-9 values ≥ 37 U/mL and pathological tumor size ≥ 30 mm (P = 0.016 and 0.038, respectively). TMPRSS4 is a potential prognostic biomarker of radical resection for BTC.

Development and Validation of a Nomogram for Predicting Postoperative Recurrence-Free Survival in Patients With Nonmetastatic Pathological T3a Stage Renal Cell Carcinoma

BackgroundTo establish a nomogram predicting postoperative recurrence-free survival (RFS) in patients with nonmetastatic renal cell carcinoma (RCC) of pathological T3a (pT3a) stage undergoing nephrectomy. Materials and MethodsA retrospective review included 668 patients with pT3a RCC between 2008 and 2019, randomly divided into training and validation groups (7:3 ratio). Cox regression analysis established the RFS-predicting nomogram in the training group. Nomogram performance was assessed using Harrell's concordance index (C-index), time-dependent receiver operating characteristic curve, decision curve analysis, and Kaplan-Meier survival analysis. ResultsOf the 668 patients with pT3a RCC, 167 patients experienced local recurrence or distant metastasis. Using multivariable Cox regression analysis, tumor size, ISUP grade, necrosis, capsular invasion, pT3a invasion pattern were identified as the significant predictors for RFS to establish the nomogram. The C-index of the nomogram was 0.753 (95% CI, 0.710-0.796) and 0.762 (95% CI, 0.701-0.822) for the training and validating group, respectively. The areas under the 1-year, 3-year and 5-year RFS receiver operating characteristic curves were 0.814, 0.769 and 0.768, respectively. Decision curve analysis showed the optimal application of the model in clinical decision-making. Patients with low risk T3a RCC have better RFS than those with high risk T3a RCC. ConclusionTumor size, ISUP grade, necrosis, capsular invasion and T3a invasion patterns were independent risk factors for worse RFS in patients with nonmetastatic pT3a RCC. The current nomogram could effectively predict the RFS of patients with nonmetastatic pT3a RCC.

Comprehensive assessment of postoperative recurrence and survival in patients with cervical cancer

BackgroundThe prediction of postoperative recurrence and survival in cervical cancer patients has been a major clinical challenge. The combination of clinical parameters, inflammatory markers, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and MRI-derived radiomics is expected to support the prediction of recurrence-free survival (RFS), disease-free survival (DFS), tumor-specific survival (CSS), and overall survival (OS) of cervical cancer patients after surgery. MethodsA retrospective analysis of 181 cervical cancer patients with continuous follow-up was completed. The parameters of IVIM-DWI and radiomics were measured, analyzed, and screened. The LASSO regularization was used to calculate the radiomics score (Rad-score). Multivariate Cox regression analysis was used to construct nomogram models for predicting postoperative RFS, DFS, CSS, and OS in cervical cancer patients, with internal and external validation. ResultsClinical stage, parametrial infiltration, internal irradiation, D-value, and Rad-score were independent prognostic factors for RFS; Squamous cell carcinoma antigen, internal irradiation, D-value, f-value and Rad-score were independent prognostic factors for DFS; Maximum tumor diameter, lymph node metastasis, platelets, D-value and Rad-score were independent prognostic factors for CSS; Lymph node metastasis, systemic inflammation response index, D-value and Rad-score were independent prognostic factors for OS. The AUCs of each model predicting RFS, DFS, CSS, and OS at 1, 3, and 5 years were 0.985, 0.929, 0.910 and 0.833, 0.818, 0.816 and 0.832, 0.863, 0.891 and 0.804, 0.812, 0.870, respectively. ConclusionsNomograms based on clinical and imaging parameters showed high clinical value in predicting postoperative RFS, DFS, CSS, and OS of cervical cancer patients and can be used as prognostic markers.

Impact of pancreatic ductal occlusion on postoperative outcomes in pancreatic head cancer patients undergoing neoadjuvant therapy

BackgroundPancreatic ductal occlusion can accompany pancreatic head cancer, leading to pancreatic exocrine insufficiency (PEI) and adverse effects on nutritional status and postoperative outcomes. We investigated its impact on nutritional status, body composition, and postoperative outcomes in patients with pancreatic head cancer undergoing neoadjuvant therapy (NAT).MethodsWe analyzed 136 patients with pancreatic head cancer who underwent NAT prior to intended pancreaticoduodenectomy (PD) between 2015 and 2022. Nutritional and anthropometric indices (body mass index [BMI], albumin, prognostic nutritional index [PNI], Glasgow prognostic score, psoas muscle index, subcutaneous adipose tissue index [SATI], and visceral adipose tissue index) and postoperative outcomes were compared between the occlusion (n = 78) and non-occlusion (n = 58) groups, in which 61 and 44 patients, respectively, ultimately underwent PD.ResultsThe occlusion group showed significantly lower post-NAT BMI, PNI, and SATI (p = 0.011, 0.005, and 0.015, respectively) in the PD cohort. The occlusion group showed significantly larger main pancreatic duct, smaller pancreatic parenchyma, and greater duct–parenchymal ratio (p < 0.001), and these morphological parameters significantly correlating with post-NAT nutritional and anthropometric indices. Postoperative 3-year survival and recurrence-free survival (RFS) rates were significantly poorer (p = 0.004 and 0.013) with pancreatic ductal occlusion, also identified as an independent postoperative risk factor for overall survival (hazard ratio [HR]: 2.31, 95% confidence interval [CI] 1.08–4.94, p = 0.030) and RFS (HR: 2.03, 95% CI 1.10–3.72, p = 0.023), in multivariate analysis.ConclusionsPancreatic ductal occlusion may be linked to poorer postoperative outcomes due to PEI-related malnutrition.

Analysis of postoperative recurrence-free survival in non–small cell lung cancer patients based on consensus clustering

This study aims to assess whether consensus clustering, based on computed tomography (CT) radiomics from both intratumoral and peritumoral regions, can effectively stratify the risk of non-small cell lung cancer (NSCLC) patients and predict their postoperative recurrence-free survival (RFS). A retrospective analysis was conducted on the data of surgical patients diagnosed with NSCLC between December 2014 and April 2020. After preprocessing CT images, radiomic features were extracted from a 9-mm region encompassing both the tumor and its peritumoral area. Consensus clustering was utilized to analyze the radiomics features and categorize patients into distinct clusters. A comparison of the differences in clinical pathological characteristics was conducted among the clusters. Kaplan-Meier survival analysis was employed to investigate differences in survival among the clusters. A total of 266 patients were included in this study, and consensus clustering identified three clusters (Cluster 1: n=111, Cluster 2: n=61, Cluster 3: n=94). Multiple clinical risk factors, including pathological TNM staging, programmed cell death ligand 1 (PD-L1), and epidermal growth factor receptor (EGFR) expression statusexhibit significant differences among the three clusters. Kaplan-Meier survival analysis demonstrated significant variations in RFS across the clusters (P<0.001). The 3-year cumulative recurrence-free survival rates were 76.5% (95% CI: 68.6-84.4) for Cluster 1, 45.9% (95% CI: 33.4-58.4) for Cluster 2, and 41.5% (95% CI: 31.6-51.5) for Cluster 3. Consensus clustering of CT radiomics based on intratumoral and peritumoral regions can stratify the risk of postoperative recurrence in patients with NSCLC.

LI-RADS Category Can Be a Post-Surgical Prognostic Factor for Intrahepatic Cholangiocarcinoma in Patients with Liver Cirrhosis or Chronic Hepatitis B

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; The Liver Imaging Reporting and Data System (LI-RADS) categorization has been proposed as a potential prognostic indicator for primary liver neoplasms in patients with liver cirrhosis or chronic hepatitis B. This multicenter study aimed to determine whether LI-RADS categorization can offer additional post-surgical prognostic value for intrahepatic cholangiocarcinoma (ICCA) when used in conjunction with the American Joint Committee on Cancer (AJCC) guidelines. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Patients with high risk for hepatocellular carcinoma, surgically confirmed ICCAs, and available preoperative MRI were enrolled. LI-RADS categorization of ICCAs was performed using MRI features, and multivariate analyses were conducted incorporating LI-RADS category, AJCC staging, and clinicopathologic factors to evaluate their predictive value for postoperative recurrence-free survival (RFS) and overall survival (OS). In patients with early recurrence (&amp;lt;2 years), the percentages of AJCC stage I and LR-M or LR tumor-in-vein (TIV) were calculated, respectively. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Among the 166 ICCAs analyzed, 13.3% (22/166) were classified as LR-4/5, 77.7% (129/166) as LR-M, and 9.0% (15/166) as LR TIV. Classifications according to the 8th AJCC guidelines for patients with available post-surgical pathologic data and follow-up imaging were 40.6% (63/155) stage I tumors, 23.9% (37/155) stage II, and 35.5% (55/155) stage III. Multivariate analysis revealed that LI-RADS category (LR-M or LR-TIV) was a significant factor for predicting both RFS (hazard ratio [HR] = 2.86, &lt;i&gt;p&lt;/i&gt; = 0.02) and OS (HR = 3.18, &lt;i&gt;p&lt;/i&gt; = 0.03). Additionally, AJCC staging (II or III) was a significant factor for RFS (HR = 3.90, &lt;i&gt;p&lt;/i&gt; &amp;lt; 0.001) and OS (HR = 3.29, &lt;i&gt;p&lt;/i&gt; &amp;lt; 0.001), male sex was a significant factor for RFS (HR = 1.89, &lt;i&gt;p&lt;/i&gt; = 0.006) and OS (HR = 2.23, &lt;i&gt;p&lt;/i&gt; = 0.002), and positive resection margin was a significant factor for OS (HR = 1.91, &lt;i&gt;p&lt;/i&gt; = 0.03). Among the 80 patients with early recurrence, 97.5% displayed LR-M or LR-TIV features, while 11.3% were AJCC stage I patients. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; The MRI-based preoperative LI-RADS categorization of ICCA provides additional post-surgical prognostic value beyond the AJCC guidelines, with significant implications for both RFS and OS.

Nomograms incorporating hsa_circ_0029325 highly expressed in exosomes of hepatocellular carcinoma predict the postoperative outcomes

BackgroundLiquid biopsies, for example, exosomal circular RNA (circRNA) can be used to assess potential predictive markers for hepatocellular carcinoma (HCC) in patients after curative resection. This study aimed to search for effective prognostic biomarkers for HCC in patients after surgical resection based on exosomal circRNA expression profiles. We developed two nomograms incorporating circRNAs to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) of HCC patients.MethodPlasma exosomes isolated from HCC patients and healthy individuals were used for circRNA microarray analysis to explore differentially expressed circRNAs. Pearson correlation analysis was used to evaluate the correlation between circRNAs and clinicopathological features. Cox regression analysis was used to explore the correlation between circRNA and postoperative survival time as well as recurrence time. A nomogram based on circRNA and clinicopathological characteristics was established and further evaluated to predict prognosis and recurrence.ResultAmong 60 significantly upregulated circRNAs and 25 downregulated circRNAs, hsa_circ_0029325 was selected to verify its power for predicting HCC outcomes. The high expression level of exosomal hsa_circ_0029325 was significantly correlated with OS (P = 0.001, HR = 2.04, 95% CI 1.41–3.32) and RFS (P = 0.009, HR = 1.62, 95% CI 1.14–2.30). Among 273 HCC patients, multivariate regression analysis showed that hsa_circ_0029325 (HR = 1.96, 95% CI 1.21–3.18), tumor size (HR = 2.11, 95% CI 1.33–3.32), clinical staging (HR = 2.31, 95% CI 1.54–3.48), and tumor thrombus (HR = 1.74, 95% CI 1.12–2.7) were independent risk factors for poor prognosis in HCC patients after radical resection. These independent predictors of prognosis were incorporated into the two nomograms. The AUCs under the 1-year, 3-year, and 5-year survival and recurrence curves of the OS and RFS nomograms were 0.755, 0.749, and 0.742 and 0.702, 0.685, and 0.642, respectively. The C-index, calibration curves, and clinical decision curves showed that the two prediction models had good predictive performance. These results were verified in the validation cohort with 90 HCC patients.ConclusionOur study established two reliable nomograms for predicting recurrence and prognosis in HCC patients. We also show that it is feasible to screen potential predictive markers for HCC after curative resection through exosomal circRNA expression profile analysis.

Patterns of recurrence after esophagectomy following neoadjuvant Immunochemotherapy for esophageal squamous cell carcinoma.

e16101 Background: To explore the recurrence pattern and risk factors of the initial relapse for esophageal squamous cell carcinoma (ESCC) who received radical surgery following neoadjuvant Immunochemotherapy (NICT). Methods: We reviewed 191 ESCC patients who underwent radical surgery following NICT from 2020 to 2022. The pattern of the first postoperative failure and simple lymph node (LN) recurrence were analyzed. Risk factors for failure were analyzed using logistic multivariate regression. Postoperative recurrence-free survival (RFS) was determined using the Kaplan-Meier method, and the log-rank test was applied to assess differences. Results: Until November 26, 2023, 66 of 191 patients experienced postoperative failure. The failure rates at 6 months, 1 year and 2 years were 7.3%, 21.0% and 37.4%, respectively. The overall recurrence pattern included single-pattern recurrence (84.8%) and multiple-pattern recurrence (15.2%). Among the single-pattern recurrence, simple LN recurrence (77%) was the most common. In total, 112 recurrent areas were observed in 43 patients with simple LN recurrence, and the failure rates of cervical, mediastinal and abdominal LNs were 15%, 70% and 15%, respectively. In patients with mediastinal LN failure, superior mediastinal LN recurrence accounted for the highest proportion (54%,60/112), of which 2R (16%,18/112) and 4R (14%,16/112) were the most frequent. The highest proportion (71.4%) of LN failure was located outside the scope of surgical dissection, and the highest incidence was in the supraclavicular area (21%) and the mediastinal 4R area (20%). According to the number of dissected LN areas, patients were divided into three groups: 1-6≤, 6-9≤, and 9-14≤. The 2-year RFS rates for three groups were 50.5%, 72.3%, and 63.5%, respectively (P = 0.04). According to the number of dissected LNs, patients were divided into three groups: 15 &lt; , 15-30 &lt; , and ≥30. The 2-year RFS rates of the three groups were 49.7%, 61.6%, and 71.6%, respectively (P = 0.28). Subgroup analysis showed that the 2-year RFS rates in ypT0-1N0 patients were 80%, 90% and 78.4% (P = 0.56), respectively, and ypT0-1N0 patients with more than 30 LNs did not show significant advantage. Multivariate analysis showed that tumor length &gt; 5 cm, preoperative efficacy evaluation of stable disease (SD), number of dissected LN areas≤6, and ypN2-3 stage were unfavorable factors for postoperative failure in patients. Conclusions: LN recurrence is a common failure mode after radical surgery following NICT for ESCC, and the LN recurrence in the mediastinal 4R and 2R regions is the most common. Tumor length &gt; 5cm, preoperative efficacy evaluation of SD, number of dissected LN areas≤6, and ypN2-3 stage were unfavorable factors for postoperative failure in patients. The suitability of extensive and multiple LN dissection after NICT in ESCC remains to be further investigated.

Impact of preoperative chemotherapy on surgical results in 139 patients with locally advanced pancreatic cancer.

The establishment of preoperative chemotherapy (PCT) with FOLFIRINOX and gemcitabine/nab-paclitaxel in recent years has enabled resectability in many patients with initially locally advanced pancreatic cancer (LAPC). Nevertheless, information about the impact of PCT on surgical results is scarce. All patients with initial LAPC who received surgery after chemotherapy at the high-volume centre for pancreatic surgery of St. Josef-Hospital Bochum between 2015 and 2022 were included in this retrospective cohort analysis. A total of 139 patients underwent surgery after pre-treatment with FOLFIRINOX (76.3%), gemcitabine/nab-paclitaxel (11.5%), both (5.8%) and other regimens (6.5%). Eighty-five tumors (61.2%) were resectable after PCT. R0 resection was achieved in 92.9%, R1 in 7.1% and R2 in 0% of cases. Fifty-four tumors were still not resectable at the time of surgery. Surgical results of the patients did not show increased postoperative mortality and morbidity compared to the literature data. Postoperative 30-day mortality was 1.4%. Rates for pancreas-specific complications [postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and others] were not increased. POPF occurred in 10.5% and DGE in 26.3% after pancreaticoduodenectomy. After distal pancreatectomy, POPF was detected in 37.5% and DGE in 12.5%. Median postoperative survival (31 vs. 13 months) and overall survival after initial diagnosis (40 vs. 20 months) were significantly longer in resected patients (P<0.001). Postoperative recurrence-free survival in resected patients amounted to 12 months. This study underlines that PCT allows resectability of primarily unresectable patients with LAPC without increasing perioperative mortality and morbidity. It may lead to a significant prolongation of recurrence-free and overall survival in resected patients after PCT.

A nomogram for preoperative prediction of vessels encapsulating tumor clusters (VETC) pattern and prognosis of hepatocellular carcinoma

BackgroundVessels encapsulating tumor clusters (VETC) pattern of hepatocellular carcinoma (HCC) are associated with unfavorable prognosis. This study aimed to establish a nomogram model to predict VETC patterns based on preoperative CT imaging features. Patients and methodsPatients who underwent surgical resection between January 1, 2016 and August 31, 2022 were retrospectively included. Predictors associated with VETC pattern were determined by using logistic regression analyses, and a nomogram model was constructed. Prognostic factors associated with recurrence-free survival (RFS) after surgical resection were identified by using Cox regression analyses. ResultsA total of 84 patients were included for CT analysis. All patients underwent radical surgical resection. AST/ALT >1.07(odds ratio [OR], 4.91; 95 ​% CI: 1.11, 21.68; P ​< ​0.05), intratumoral necrosis (OR, 4.99; 95 ​% CI: 1.25, 19.99; P ​< ​0.05) and enhancing capsule (OR, 3.32; 95 ​% CI: 1.27, 8.94; P ​< ​0.05) were independent predictors of VETC pattern. These features were used for the construction of nomogram model, which showed comparable prediction performance, with AUC value of 0.767 (95%CI [0.662, 0.852]). CK19 status (Hazard ratio [HR], 2.02; 95 ​% CI: 1.06, 3.86; P ​< ​0.05), the number of tumors (HR, 3.31; 95 ​% CI: 1.47, 7.45; P ​< ​0.05) and VETC pattern (HR, 2.52; 95 ​% CI: 1.31, 4.86; P ​< ​0.05) were independent predictors of postoperative RFS. ConclusionA nomogram model based on preoperative CT imaging features could be used for the characterization of VETC pattern, and has prognostic significance for postoperative RFS in patients with HCC.

A retrospective study of postoperative adjuvant therapy following immunotherapy combined with targeted therapy and sequential curative surgical procedures for initially unresectable hepatocellular carcinoma

Objective: To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma. Methods: This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People's Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer(BCLC) stage C. Survival curves were made using Kaplan Meier method. Results: Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95%CI:93.4% to 100%) and 90.7%(95%CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95%CI:83.0% to 99.8%) and 71.3%(95%CI:58.7% to 86.5%). Conclusions: The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Postoperative long‑term outcomes of acute normovolemic hemodilution in pancreatic cancer: A propensity score matching analysis.

Acute normovolemic hemodilution (ANH) is a useful intraoperative blood conservation technique. However, the impact on long-term outcomes in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The present study investigated the impact of ANH on long-term outcomes in patients with PDAC undergoing radical surgery. Data from 155 resectable PDAC cases were collected. Patients were categorized according to whether or not they had received intraoperative allogeneic blood transfusion (ABT) or ANH. Postoperative complications, recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ANH. A total of 44 patients (28.4%) were included in the ANH group and 30 patients (19.4%) were included in the ABT group; 81 (52.3%) patients, comprising the standard management (STD) group, received neither ANH nor ABT. The ABT group had the worst prognosis among them. Before PSM, ANH was significantly associated with decreased RFS (P=0.043) and DSS (P=0.029) compared with the STD group before applying Bonferroni correction; however, no significant difference was observed after applying Bonferroni correction. Cox regression analysis identified ANH as an independent prognostic factor for RFS [relative risk (RR), 1.696; P=0.019] and DSS (RR, 1.876; P=0.009). After PSM, the ANH group exhibited less favorable RFS [median survival time (MST), 12.1 vs. 18.1 months; P=0.097] and DSS (MST, 32.1 vs. 50.5 months; P=0.097) compared with the STD group; however, these differences were not statistically significant. In conclusion, while ANH was not as harmful as ABT, it exhibited potentially more negative effects on long-term postoperative outcomes in PDAC than STD.

Abstract 3962: A CCR6+Th1-like CD4+T-cell cluster involved in HEV formation predicted lung cancer patients requiring anti-CTLA-4 therapy

Abstract Background: CD4+ T cells are known to help in cytotoxic T-cell priming, clonal proliferation, migratory and infiltrative capacity, and target cell killing function by licensing dendritic cells. Although CXCR3+ CCR6- classical Th1 CD4+ T cells are thought to be essential for acute cellular immunity, such as antiviral responses, the details of Th1-type CD4+ T cells required for anti-tumor immunity as a long-term chronic T cell immune responses over years remain unclear. We reported the Th7R, a CCR6 expressing Th1-like CD4+ T cell cluster predicted anti-PD-1 antibody therapy efficacy and postoperative recurrence-free survival. Objective: In this study, we focus on two Th1-like CD4+ T cell clusters, Th1 and Th7R, to determine their functions and roles in long-lasting anti-tumor immune phenomena. Methods: We studied patients with advanced stage lung cancer treated with immune checkpoint inhibitors (Pembrolizumab monotherapy n=63, Ipilimumab + Nivolumab n=148) and stage I-II lung cancer patients undergoing surgery (n=54). Mass cytometry, single cell RNA sequencing, and immunohistochemical staining were performed using peripheral blood, tumor-infiltrating lymphocytes and lymph node T cells. These studies were approved by the IRB of Saitama Medical University International Medical Center, and all patients gave written consent. Results: Unlike classical Th1, which highly expresses PRF1, GZMB, GNLY, and NKG7, Th7R expressed LTβ, CXCR6, CTLA-4, CD28, and CXCL13. Analysis of HEV index (MECA79+/CD31+ vessels) by MECA79 and CD31 staining of tumor tissues showed that Th7R in peripheral blood correlated with tumor tissue HEV index, suggesting that LTβ and CXCL13 expressed by Th7R are involved in HEV formation.Th1 mainly expressed PD-1 and did not express CTLA-4, whereas Th7R expressed both PD-1 and CTLA-4. When pre-treatment peripheral Th7R quartile was used to analyze OS after Ipilimumab + Nivolumab treatment, both the top 25% and intermediate 50% patients showed favorable prognosis, but the lower 25% had significantly poor OS. In contrast, only the top 25% Th7R patients but not the intermediate 50% and lower 25% patients who were treated with Pembrolizumab had favorable OS. Thus, it is likely that the Th7R intermediate 50% patients required anti-CTLA-4 therapy to achieve antitumor immune responses. These results may be useful for stratification of patients requiring anti-CTLA-4 antibody therapy as well as for predicting the therapeutic response of Ipilimumab + Nivolumab. Conclusion: Th7R exhibits LTβ and CXCL13 expression, which is absent in classical Th1, and may help maintain sustained T-cell immunity through HEV/TLS formation. Th7R may be a biomarker to select the patients who benefit from anti-CTLA-4 treatment. Citation Format: Hiroshi Kagamu, Satoshi Yamasaki, Atsuhito Mouri, Ou Yamaguchi, Ayako Shiono, Fuyumi Nishihara, Yu Miura, Kosuke Hashimoto, Hisao Imai, Kyoichi Kaira, Kunihiko Koabayashi, Katsuhisa Horimoto. A CCR6+Th1-like CD4+T-cell cluster involved in HEV formation predicted lung cancer patients requiring anti-CTLA-4 therapy [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 3962.

Contrasting Roles of Programmed Death-Ligand 1 Expression in Tumor and Stroma in Prognosis of Esophageal Squamous Cell Carcinoma.

The assessment of programmed death-ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) has become increasingly important with the rise of immune checkpoint inhibitors (ICIs). However, challenges persist, including subjective interpretation and the unclear significance of staining intensity, as well as contrasting roles in tumoral and stromal regions. Our study enhances the understanding of PD-L1 in ESCCs by analyzing its expression in tumors and stroma with H-scores, highlighting its distinct clinicopathological impacts. In a retrospective cohort of 194 ESCC specimens from surgical resection, we quantified PD-L1 expression in tumoral and stromal compartments using H-scores, analyzing whole slide images with digital pathology analysis software. Kaplan-Meier analysis demonstrated that higher PD-L1 expression is significantly associated with improved postoperative overall survival (OS) and recurrence-free survival (RFS) in both tumoral and stromal areas. Multivariable analysis identified high tumoral PD-L1 expression as an independent prognostic factor for prolonged OS and RFS (HR = 0.47, p = 0.007; HR = 0.54, p = 0.022, respectively). In a separate analysis, high stromal PD-L1 expression was found to correlate with less advanced pathological stages and a prolonged response to cytotoxic chemotherapy, with no similar correlation found for ICI treatment response. This study reveals PD-L1's contrasting role in the ESCC tumor immune microenvironment, impacting prognosis, tumor stage, and treatment response.

The effect of spread through air spaces on postoperative recurrence-free survival in patients with multiple primary lung cancers

PurposeThe purpose of the study was to investigate the effect of spread through air spaces (STAS) on the postoperative prognosis of patients with multiple primary lung cancers staged from IA to IB based on tumor size.MethodsClinicopathological and follow-up data of 122 patients with multiple primary lung cancers diagnosed at stages IA-IB and surgically treated at the Department of Thoracic Surgery, Shenzhen people’s Hospital from January 2019 to December 2021 were retrospectively analyzed. The study involved 42 males and 80 females. STAS status was used to divide them into two groups (87 cases in STAS (-) and 35 cases in STAS (+)). A logistic regression analysis, univariate and multivariate Cox regression analysis, and Kaplan-Meier curves (K-M) were used to determine how STAS affected recurrence-free survival (RFS) in patients.ResultsSTAS (+) had a significantly higher recurrence rate than STAS (-). STAS was predicted by smoking history (P = 0.044), main tumor diameter (P = 0.02), and solid nodules on chest CT (P = 0.02). STAS incidence was not significantly different between lobectomy and sublobar resection groups (P = 0.17). Solid nodules on CT, tumor diameter, vascular invasion, pleural invasion, and STAS were significant predictors of recurrence in the univariate Cox regression analysis. Tumor diameter, pleural invasion and STAS were significant prognostic factors for recurrence in the multivariate Cox regression analysis. Furthermore, STAS (+) group was at greater risk of recurrence than STAS (-) group (34% vs. 0%, P < 0.05)。.ConclusionStage IA-IB multiple primary lung cancer patients with STAS (+) had a higher recurrence rate and a shorter overall survival rate.

Trajectories of neutrophil-to-lymphocyte ratios during neoadjuvant chemotherapy correlate with short- and long-term outcomes in gastric cancer: a group-based trajectory analysis

BackgroundSystemic inflammatory factors can predict the survival prognosis of gastric cancer (GC) patients after neoadjuvant chemotherapy (NACT). However, whether longitudinal changes in systemic inflammatory factors are associated with short - and long-term outcomes has not been reported.MethodsThis study is a retrospective analysis of 216 patients with advanced gastric cancer who received NACT between January 2011 and June 2019, comparing receiver operating characteristic (ROC) curves for screening suitable inflammatory markers. Group-based trajectory modeling (GBTM) was used to analyze longitudinal changes in inflammatory markers during NACT to identify different potential subgroups and to compare postoperative complications, recurrence-free survival (RFS), and overall survival (OS) among subgroups.ResultsUltimately, neutrophil-lymphocyte ratio (NLR) had the highest area under the curve (AUC) value in predicting prognosis was included in the GBTM analysis. Three trajectories of NLR were obtained: Stable group (SG) (n = 89), Ascent-descend group (ADG) (n = 80) and Continuous descend group (CDG) (n = 47). Compared with SG, ADG and CDG are associated with an increased risk of postoperative recurrence and death. The median time of RFS and OS of SG was longer than that of ADG and CDG (median RFS 81 vs. 44 and 22 months; median OS 69 vs. 41 and 30 months). In addition, CDG had significantly higher postoperative serious complications than SG and ADG (17 (36.2%) vs. 17 (19.1%) and 12 (15.0%); p = 0.005).ConclusionThere were different trajectories of NLR during NACT, and these potential trajectories were significantly associated with severe postoperative complications, recurrence, and mortality in patients with GC.

High serum alpha-fetoprotein and positive immunohistochemistry of alpha-fetoprotein are related to poor prognosis of gastric cancer with liver metastasis

Liver metastasis in gastric cancer is incurable. Alpha-fetoprotein-producing gastric cancer has a poor prognosis and is prone to liver metastasis. We investigated the association between preoperative serum alpha-fetoprotein levels, liver metastasis, and expression of primitive enterocyte phenotype markers. We reviewed the medical records of 401 patients with gastric cancer who underwent curative surgical resection and immunohistochemically evaluated the primitive phenotype markers. The preoperative serum alpha-fetoprotein levels were elevated and normal in 8 and 393 patients, respectively. Liver metastasis was more frequent in patients with higher preoperative alpha-fetoprotein levels. The 5-year postoperative recurrence-free survival and overall survival rates were significantly worse in patients with higher preoperative serum alpha-fetoprotein levels. Although alpha-fetoprotein and Glypican3 and Spalt-like transcription factor 4 tended to be stained with high preoperative serum alpha-fetoprotein levels, these markers were also positive in some patients with normal alpha-fetoprotein levels. In summary, patients with gastric cancer and high preoperative serum alpha-fetoprotein levels have a poor prognosis and high incidence of liver metastasis. Alpha-fetoprotein can help detect liver metastasis relating to the primitive enterocyte phenotype.