Independent Prognostic Factor For Recurrence-free Survival Research Articles

A Machine Learning-Based Clustering Using Radiomics of F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for the Prediction of Prognosis in Patients with Intrahepatic Cholangiocarcinoma

Background: Intrahepatic cholangiocarcinoma (IHCC) is highly aggressive primary hepatic malignancy with an increasing incidence. Objective: This study aimed to develop machine learning-based radiomic clustering using F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for predicting recurrence-free survival (RFS) and overall survival (OS) in IHCC. Methods: We retrospectively reviewed pretreatment F-18 FDG PET/CT scans of 60 IHCC patients who underwent surgery without neoadjuvant treatment between January 2008 and July 2020. Radiomic features such as first order, shape, and gray level were extracted from the scans of 52 patients and analyzed using unsupervised hierarchical clustering. Results: Of the 60 patients, 36 experienced recurrence and 31 died during follow-up. Eight patients with a negative FDG uptake were classified as Group 0. The unsupervised hierarchical clustering analysis divided the total cohort into three clusters (Group 1: n = 27; Group 2: n = 23; Group 3: n = 2). The Kaplan–Meier curves showed significant differences in RFS and OS among the clusters (p < 0.0001). Multivariate analyses showed that the PET radiomics grouping was an independent prognostic factor for RFS (hazard ratio (HR) = 3.03, p = 0.001) and OS (HR = 2.39, p = 0.030). Oxidative phosphorylation was significantly activated in Group 1, and the KRAS, P53, and WNT β-catenin pathways were enriched in Group 2. Conclusions: This study demonstrated that machine learning-based PET radiomics clustering can preoperatively predict prognosis and provide valuable information complementing the genomic profiling of IHCC.

Depth of Radiographic Response as an Independent Prognostic Factor for Patients with Initially Unresectable Hepatocellular Carcinoma Receiving Hepatectomy following Targeted Therapy plus Immunotherapy

Introduction: Surgical resection following systemic therapy is feasible in patients with initially unresectable hepatocellular carcinoma (HCC). However, postoperative tumor recurrence is common after surgery, and the factors affecting this recurrence remain unclear. This study aimed to assess factors influencing postoperative outcomes in patients with initially unresectable HCC undergoing hepatectomy after systemic therapy. Methods: This study retrospectively enrolled patients with initially unresectable HCC who underwent hepatectomy after targeted therapy plus immunotherapy (with or without locoregional therapy). Multivariate Cox regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS) and overall survival (OS). Machine learning was used to determine the RFS rates at different intervals for different radiographic responses. Results: Eighty-one patients who underwent R0 hepatectomy after systemic therapy were included. With a median follow-up of 17.4 (interquartile range: 7.2–22.3) months, median RFS and OS were not reached. Preoperative tumor downstaging and achieving pathological complete response were associated with improved RFS and OS. Multivariate Cox analyses identified radiographic response as an independent prognostic factor for RFS and OS. Furthermore, a radiographic response >40% (assessed using the Response Evaluation Criteria in Solid Tumors, version 1.1) or >50% (assessed using the modified Response Evaluation Criteria in Solid Tumors) was associated with a longer RFS (p = 0.006 and 0.003, respectively). Conclusion: Radiographic response depth was an independent prognostic factor in patients with initially unresectable HCC who underwent hepatectomy following targeted therapy plus immunotherapy, and the response to systemic therapy may be the determining factor for patient prognosis after surgery.

Chromosomal instability is associated with prognosis and efficacy of bevacizumab after resection of colorectal cancer liver metastasis

Introduction Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab. Methods Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan–Meier method and Cox regression models. Results Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001–3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150–5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078–6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173–12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043). Conclusions Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6–VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.

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.

Prognostic Value of Preoperative N Subcategories in Patients with Stage IIIA N2 Non-Small Cell Lung Cancer.

Purpose To evaluate the preoperative risk factors in patients with pathologic IIIA N2 non-small cell lung cancer (NSCLC) who underwent upfront surgery and to evaluate the prognostic value of new N subcategories. Materials and Methods Patients with pathologic stage IIIA N2 NSCLC who underwent upfront surgery in a single tertiary center from January 2015 to April 2021 were retrospectively reviewed. Each patient's clinical N (cN) was assigned to one of six subcategories (cN0, cN1a, cN1b, cN2a1, cN2a2, and cN2b) based on recently proposed N descriptors. Cox regression analysis was used to identify the significant prognostic factors for recurrence-free survival (RFS) and overall survival (OS). Results A total of 366 patients (mean age ± SD, 62.0 years ± 10.1; 202 male patients [55%]) were analyzed. The recurrence rate was 55% (203 of 366 patients) over a median follow-up of 37.3 months. Multivariable analysis demonstrated that cN (hazard ratios [HRs] for cN1 and cN2b compared with cN0, 1.66 [95% CI: 1.11, 2.48] and 2.11 [95% CI: 1.32, 3.38], respectively) and maximum lymph node (LN) size at N1 station (≥12 mm; HR, 1.62 [95% CI: 1.15, 2.29]), in addition to clinical T category (HR, 1.51 [95% CI: 1.14, 1.99]), were independent prognostic factors for RFS. For OS, clinical N subcategories (cN1, cN2a2, and cN2b vs cN0; HRs, 1.91 [95% CI: 1.11, 3.27], 1.89 [95% CI: 1.13, 2.18], and 2.02 [95% CI: 1.07, 3.80], respectively) and LN size at N1 station (HR, 1.75 [95% CI: 1.12, 2.71]) were independent prognostic factors. For clinical N1, OS was further stratified according to LN size (log-rank test, P < .001). Conclusion Assessing the proposed N subcategories by reporting single versus multistation involvement of N2 disease and maximum size of metastatic LN, reflecting metastatic burden, at preoperative CT may offer useful prognostic information for planning optimal treatment strategies. Keywords: CT, Lung, Staging, Non-Small Cell Lung Cancer Supplemental material is available for this article. ©RSNA, 2024.

Prognostic effect of microscopically negative but close resection margin in gastric cancer

IntroductionMicroscopically positive resection margin (RM) following curative surgery has been linked to disease recurrence in gastric cancer (GC), but the impact of microscopically negative but close RM (CRM) remains unclear. This study aimed to evaluate the prognostic implications of a CRM of ≤0.5 cm in GC patients. MethodsA retrospective review of the institutional GC database identified 1958 patients who underwent curative gastrectomy for pathologically proven GC between January 2011 and December 2015. The patients were categorized into CRM (RM ≤0.5 cm) and sufficient RM (SRM, RM >0.5 cm) groups. The impact of CRM on recurrence-free survival (RFS) and overall survival (OS) was analyzed compared to the SRM group. ResultsThe cohort comprised 1264 patients with early GC (EGC, 64.6%) and 694 with advanced GC (AGC, 35.4%). Forty-four patients (2.2%) had RM of ≤0.5 cm. CRM was associated with worse RFS in AGC (5-year RFS in the CRM vs. SRM groups; 41.6% vs. 68.7%, p = 0.011); however, the effect on OS was not significant (p = 0.159). Multivariate analysis revealed that CRM was an independent prognostic factor for RFS (hazard ratio [HR] 2.035, 95% confidence interval [CI] 1.097–3.776). In AGC, the locoregional recurrence rate was significantly higher in the CRM group than in the SRM group (15.4% vs. 4.9%, p = 0.044). ConclusionCRM of ≤0.5 cm was a significant prognostic factor for RFS in GC patients and was associated with a significant increase in locoregional recurrence in AGC.

Association Between Preoperative Osteopenia and Prognosis in Breast Cancer Patients.

Osteopenia, the loss of bone mineral density (BMD), was recently reported as a prognostic factor in various cancers. However, the prognostic significance of preoperative osteopenia in breast cancer remains unclear. This study aimed to clarify the clinical significance of preoperative osteopenia in breast cancer. We retrospectively analyzed the relationship between osteopenia and clinical factors and prognosis in 532 patients with pathological Stage I-III primary breast cancer between 2009 and 2017. Osteopenia was assessed by measuring the average pixel density (Hounsfield unit) in the midvertebral core of the 11th thoracic vertebra on enhanced preoperative computed tomography. Osteopenia was diagnosed in 186 (35.0%) patients. The recurrence-free survival (RFS) rate was significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0275), but there was no significant difference in overall survival (OS) between the two groups. When evaluated by menopausal status, RFS and OS were significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0094 and p=0.0264, respectively) in premenopausal patients. However, there were no significant differences in RFS and OS between the two groups among postmenopausal patients. In premenopausal patients, osteopenia was an independent prognostic factor for RFS in a multivariate analysis (p=0.0266). Preoperative osteopenia was independently associated with recurrence of breast cancer.

Prognostic significance of pan-immune-inflammation value in hepatocellular carcinoma treated by curative radiofrequency ablation: potential role for individualized adjuvant systemic treatment

Background This study aimed to explore the prognostic role of pan-immune-inflammation value (PIV) and develop a new risk model to guide individualized adjuvant systemic treatment following radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC). Materials and methods Patients with early-stage HCC treated by RFA were randomly divided into training cohort A (n = 65) and testing cohort B (n = 68). Another 265 counterparts were enrolled into external validating cohort C. Various immune-inflammatory biomarkers (IIBs) were screened in cohort A. Prognostic role of PIV was evaluated and validated in cohort B and C, respectively. A nomogram risk model was built in cohort C and validated in pooled cohort D. Clinical benefits of adjuvant anti-angiogenesis therapy plus immune checkpoint inhibitor (AA-ICI) following RFA was assessed in low- and high-risk groups. Results The cutoff point of PIV was 120. High PIV was an independent predictor of unfavorable recurrence-free survival (RFS) and overall survival (OS). RFS and OS rates of patients with high PIV were significantly lower than those with low PIV both in cohort B (P RFS=0.016, P OS=0.011) and C (P RFS<0.001, P OS<0.001). The nomogram model based on PIV, tumor number and BCLC staging performed well in risk stratification in external validating cohort C. Adjuvant AA-ICI treatment showed an added benefit in OS (p = 0.011) for high-risk patients. Conclusions PIV is a feasible independent prognostic factor for RFS and OS in early-stage HCC patients who received curative RFA. The proposed PIV-based nomogram risk model could help clinicians identify high-risk patients and tailor adjuvant systemic treatment and disease follow-up scheme.

Abstract PO3-02-11: Impact of Tumor Volume on Oncologic Outcomes in Patients with T1 Breast Cancer: A Retrospective Analysis

Abstract Backgrounds: Measuring the extent of tumor cell accretion in the primary organ typically involves assessing the longest diameter, an important component of the widely employed TNM staging system. The largest tumor diameter is considered indicative of the risk of cancer metastasis and the likelihood of distant recurrences. However, relying solely on the unidimensional diameter to determine the degree of cancer cell accretion can be inadequate since each tumor has a unique three-dimensional shape, thus leading to different tumor volumes. Purpose: The aim of this study was to investigate the impact of tumor volume on oncologic outcomes in patients with T1-2 breast cancer. Method: We retrospectively reviewed the medical records of 1,018 patients diagnosed with invasive breast cancer who underwent breast-conserving surgery at Seoul National University Bundang Hospital from 2010 to 2015. Patients with multiple tumors, positive margins leading to mastectomy, or those who received neoadjuvant chemotherapy were excluded. Tumor volume was defined as the product of the length of the three axes to simplify the calculation. Recurrence-free survival (RFS) was estimated by the Kaplan-Meier analysis. Result: The median value for tumor volume was 7.502 cm³. Out of 1,018 patients, 124 patients exhibited tumor volumes greater than the median value. Higher tumor volume was associated with pathologic T stage (P &amp;lt; 0.001), pathologic N stage (P = 0.004), histologic grade (P &amp;lt; 0.001), and luminal B subtype (P = 0.008). In multivariable logistic regression analyses for recurrence, higher tumor volume (OR 3.532, 95% CI 1.708-7.303, P = 0.001), CEA elevation (OR 6.129, 95% CI 1.497-25.092, P = 0.012), pN stage (OR 2.038, 95% CI 1.005-4.132, P = 0.048), and luminal B subtype (OR 2.407, 95% CI 1.060-5.470, P = 0.036) were shown to be predictive factors for recurrence, while completion of radiation therapy (OR 0.142, 95% CI 0.050-0.402, P &amp;lt; 0.001) and completion of hormone therapy (OR 0.200, 95% CI 0.047-0.849, P = 0.029) were identified as protective factors. The 5-year RFS was significantly lower in patients with higher tumor volume compared to those with lower volume (97.4% vs. 91.9%; p &amp;lt; 0.001). In multivariable Cox regression analysis, tumor volume (HR 3.056, 95% CI 1.572-5.940, P = 0.001), CEA elevation (HR 4.934, 95% CI 1.437-16.935, P = 0.011), luminal B subtype (HR 2.336, 95% CI 1.076-5.073, P = 0.032), completion of RT (HR 0.131, 95% CI 0.053-0.325, P &amp;lt; 0.001), and completion of HTx (HR 0.199, 95% CI 0.060-0.655, P = 0.008) were identified as independent prognostic factors for RFS. Conclusion: In the current study, we showed higher tumor volume results in poorer oncologic outcomes in patients with T1-2 breast cancer. Therefore, the T stage based on tumor volume, which includes all three-dimensional measurements, can better predict the prognosis in breast cancer patients than the traditional T stage that is solely dependent on the unidimensional longest tumor diameter. Citation Format: Hyoung Won Koh, Eun-Kyu Kim, Hee-Chul Shin. Impact of Tumor Volume on Oncologic Outcomes in Patients with T1 Breast Cancer: A Retrospective Analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-11.

Diacylglycerol kinase alpha is a proliferation marker of intrahepatic cholangiocarcinoma associated with the prognosis.

Intrahepatic cholangiocarcinoma (ICC) has a high recurrence rate and a poor prognosis. Thus, the development of effective treatment and prognostic biomarkers is required. High expression of diacylglycerol kinase alpha (DGKα) is a prognostic factor for the recurrence of hepatocellular carcinoma. However, the relationship between DGKα expression and prognosis in ICC has not been reported. Immunohistochemistry (IHC) with anti-DGKα antibody was performed on surgical specimens of ICC (n = 69). First, DGKα expression in cancer cells was qualitatively classified into four groups (-, 1+, 2+, 3+) and divided into two groups (DGKα- and DGKα+1 + to 3+). The relationship between clinical features and DGKα expression was analyzed. Second, Ki-67 expression was evaluated as a cell proliferation marker. The number of Ki-67-positive cells was counted, and the relationship with DGKα expression was examined. DGKα IHC divided the patients into a DGKα+ group (1+: n = 15; 2+: n = 5; 3+: n = 5) and a DGKα- group (-: n = 44). In the DGKα+ group, patients were older and had advanced disease. Both overall survival and recurrence-free survival (RFS) were significantly worse in the DGKα+ patients. DGKα+ was identified as an independent prognostic factor for RFS by multivariate analysis. Furthermore, the number of Ki-67-positive cells increased in association with the staining levels of DGKα. Pathological DGKα expression in ICC was a cancer proliferation marker associated with recurrence. This suggests that DGKα may be a potential therapeutic target for ICC.

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.

Clinical and Prognostic Significance of Glutathione Peroxidase 2 in Lung Adenocarcinoma.

Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme with an important role in tumor progression in various cancers. However, the clinical significance of GPX2 in lung adenocarcinoma has not been clarified. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze GPX2 mRNA expression. Then, we conducted immunohistochemistry (IHC) to assess GPX2 expression in specimens acquired from 351 patients with lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We investigated the association between GPX2 expression and clinicopathological characteristics and further analyzed the prognostic relevance. qRT-PCR revealed that GPX2 mRNA expression was notably higher in tumor cells than in normal tissues. IHC revealed that high GPX2 expression (n = 175, 49.9%) was significantly correlated with male sex, smoking, advanced pathological stage, and the presence of pleural, lymphatic, and vascular invasion. Patients with high GPX2 expression exhibited significantly shorter recurrence-free survival (RFS) and overall survival. Multivariate analysis identified high GPX2 expression as an independent prognostic factor of RFS. GPX2 expression was significantly associated with pathological malignancy. It is conceivable that high GPX2 expression reflects tumor malignancy. Therefore, high GPX2 expression is a significant prognostic factor of poor prognosis for completely resected lung adenocarcinoma.

Prognostic significance and survival benefits of postoperative adjuvant chemotherapy in patients with stage IA lung adenocarcinoma with non-predominant micropapillary components

BackgroundThe prognostic significance of adjuvant chemotherapy (ACT) for patients with stage IA micropapillary non-predominant (MPNP) lung adenocarcinoma (LUAD) remains unknown. This study aimed to investigate the effects of postoperative ACT in patients with stage IA MPNP-LUAD.MethodsA total of 149 patients with pathological stage IA MPNP-LUAD who underwent surgery at our center were retrospectively analyzed. Propensity score matching (PSM) analysis was conducted to reduce potential selection bias. Kaplan–Meier analyses were used to assess the impact of ACT on recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS). Subgroup analyses were performed for the survival outcomes based on the percentage of micropapillary components. Cox proportional hazards regression analyses were applied to identify risk factors associated with survival.ResultsThe receipt or non-receipt of postoperative ACT had no significant effect on RFS, OS, and DSS among all enrolled patients with stage IA MPNP-LUAD (P > 0.05). For patients with a micropapillary component > 5%, the 5-year rates of RFS, OS, and DSS were significantly higher in the ACT group compared to the observation group, both before and after PSM (P < 0.05). However, the differences between the two groups were not significant for patients with a micropapillary component ≤ 5% (P > 0.05). The resection range (HR = 0.071; 95% CI: 0.020–0.251; P < 0.001), tumor size (HR = 2.929; 95% CI: 1.171–7.330; P = 0.022), and ACT (HR = 0.122; 95% CI: 0.037–0.403; P = 0.001) were identified as independent prognostic factors for RFS through Cox regression analysis.ConclusionPatients with stage IA MPNP-LUAD who have a micropapillary component greater than 5% might benefit from postoperative ACT, while those with a micropapillary component ≤ 5% did not appear to derive the same benefit from postoperative ACT.

Infiltrating characteristics and prognostic value of tertiary lymphoid structures in resected gastric neuroendocrine neoplasm patients.

Tertiary lymphoid structures (TLSs) are lymphocyte aggregates that play an anti-tumor role in most solid tumors. However, the functions of TLS in gastric neuroendocrine neoplasms (GNENs) remain unknown. This study aimed to determine the characteristics and prognostic values of TLS in resected GNEN patients. Haematoxylin-eosin, immunohistochemistry (IHC) and multiple fluorescent IHC staining were used to assess TLS to investigate the correlation between TLSs and clinicopathological characteristics and its prognostic value. Tertiary lymphoid structures were identified in 84.3% of patients with GNEN. They were located in the stromal area or outside the tumor tissue and mainly composed of B and T cells. A high density of TLSs promoted an anti-tumor immune response in GNEN. CD15+ TANs and FOXP3+ Tregs in TLSs inhibited the formation of TLSs. High TLS density wassignificantly associated with prolonged recurrence-free survival(RFS) and overall survival (OS) of GNENs. Univariate and multivariate Cox regression analyses revealed that TLS density, tumor size, tumor-node-metastasis (TNM) stage and World Health Organisation (WHO) classification were independent prognostic factors for OS, whereas TLS density, tumor size and TNM stage were independent prognostic factors for RFS. Finally, OS and RFS nomograms were developed and validated, which were superior to the WHO classification and the TNM stage. Tertiary lymphoid structures were mainly located in the stromal area or outside the tumor area, and high TLS density was significantly associated with the good prognosis of patients with GNEN. Incorporating TLS density into a nomogram may improve survival prediction in patients with resected GNEN.

Lymph node ratio as an indicator of nodal status in the assessment of survival and recurrence in vulvar cancer: A cohort study.

Inguinal lymph node (LN) metastasis and particularly the number of metastatic lymph nodes (NMLN) represent a determinant prognostic factor in vulvar squamous cell carcinoma (VSCC). However, the NMLN may be related to the number of removed LNs. Therefore, the lymph node ratio (LNR) reflects not only the burden of LN involvement but also the quality and extent of lymphadenectomy. To investigate the value of the LNR and the count of LN on overall survival (OS) and recurrence-free survival (RFS). This study is a retrospective, longitudinal, institution-based study. This study included 192 patients treated for VSCC at the Salah Azaiez Institute between 1994 and 2022. Clinical, pathological, and evolutionary data were reported. Survival curves were generated by the Kaplan-Meier method, and predictive factors of outcome were analyzed using Cox proportional hazards models. Surgery consisted of a radical vulvectomy, hemivulvectomy, and pelvic exenteration in, respectively, 96.4%, 2.1%, and 1.6% of cases followed by adjuvant radiotherapy in 38.5% of cases. LN dissection was bilateral in 88.5% of cases. LNR = 0, LNR = 0-0.2, and LNR ⩾0.2 were recorded in, respectively, 64.7%, 22.1%, and 13.2% of cases. With a mean follow-up time of 35 ± 42.06 months, the 5-year OS was 52.5% and the 5-year RFS was 55.8%. On multivariate analysis, the independent prognostic factors of OS were the LNR (hazard ratio (HR) = 5.702; 95% confidence interval (CI) = 2.282-14.245; p < 0.0001), Federation of Gynecology and Obstetrics (FIGO) stage (HR = 2.089; 95% CI = 1.028-4.277; p = 0.042), and free margins (HR = 2.247; 95% CI = 1.215-4.155; p = 0.01). Recurrences were recorded in 37.5% of cases. Independent prognostic factors of RFS were the LNR (HR = 2.911; 95% CI = 1.468-5.779; p = 0.002), FIGO stage (HR = 1.835; 95% CI = 1.071-3.141; p = 0.027), and free margins (HR = 2.091; 95% CI = 1.286-3.999; p = 0.003). Surgical margin, FIGO stage, and LNR represent the independent prognostic factors of survival and LNR showed superior prognostic predictive accuracy compared with the revised 2021 FIGO staging system for predicting OS and RFS in VSCC.

The Naples Prognostic Score Is an Independent Prognostic Factor for Gastric Cancer Patients Who Receive Curative Treatment.

This study aimed to evaluate the clinical impact of the Naples Prognostic Score (NPS) in patients with gastric cancer and to clarify the potential of the NPS as a nutritional and inflammation evaluation system. This study included 158 patients who underwent curative treatment for gastric cancer between 2005 and 2020. The prognosis and clinical pathological parameters of the high-NPS (NPS >2) and low-NPS (NPS=0, 1) groups were analyzed. The overall survival (OS) rates at 3 and 5 years were 86.7% and 77.7%, respectively, in the low-NPS group and 55.4% and 47.4%, respectively, in the high-NPS group. There were significant differences in OS between the two groups. Uni- and multivariate analyses demonstrated that the NPS was an independent prognostic factor for OS (HR=2.495, 95%CI=1.240-5.451). In addition, the 3- and 5-year recurrence-free survival (RFS) rates were 82.1% and 76.0%, respectively, in the NPS-low group, and 43.8% and 36.6% in the NPS-high group. Univariate and multivariate analyses demonstrated that the NPS was an independent prognostic factor for RFS (HR=2.739, 95%CI=1.509-4.972). When the first site of recurrence was compared between the low-NPS group and high-NPS group, there were significant differences in peritoneal recurrence (8.7% vs. 34.3%, p=0.001) and hematologic recurrence (5.6% vs. 21.9%, p=0.004). The NPS was a significant prognostic factor in patients with gastric cancer who received curative treatment. The NPS may be a promising biomarker for the treatment and management of gastric cancer.

Prognostic significance of positive lymph node regression grade to neoadjuvant chemoradiation for esophageal squamous cell carcinoma.

To assess the relationship between metastatic lymph node (LN) responder status and recurrence-free survival (RFS) in patients undergoing neoadjuvant chemoradiotherapy (NCRT). We retrospectively reviewed 304 patients with local advanced esophageal squamous cell carcinoma received NCRT followed by esophagectomy. For 112 patients with positive node, according to the proportion of residual viable tumor cells area within the whole tumor beds of all metastatic LNs, we classified LN-tumor regression grade (LN-TRG) into four categories: grade 1, 0%; 2, <10%; 3, 10%-50%; 4, >50%. Patients with grade 1-2 LN-TRG of were considered LN responders, and those with grades 3-4, as LN nonresponders. Univariate and multivariate analyses of RFSwere estimated by a Cox regression model, Kaplan-Meier curve, and log-rank test. The median follow-up time of a total of 112 patients was 29.6 months. Fifty-two (46.4%) patients have experienced recurrence. In Cox univariate analysis, differentiation, AJCC stage LN responder status, nerve invasion, and lymphovascular invasion significantly correlated with RFS. Multivariate analysis for RFS revealed that LN responder status and AJCC stage (p < 0.05) were independent prognostic factor. The 3-year RFS rates for patients with LN-TRG of 1-4 grades were 72.7%, 76.5%, 37.4%, and 28.5%, respectively, and the median RFS times were not reach, 43.56, 28.09, and 22.77, respectively. LN responder status is an independent prognostic factor for RFS in esophageal cancer patients who received NCRT.

Surgical outcomes of hepatocellular carcinoma with extrahepatic bile duct tumor thrombus: a multicenter study.

The long-term prognosis after surgery of patients with hepatocellular carcinoma (HCC) and extrahepatic bile duct tumor thrombus (Ex-BDTT) remains unknown. We aimed to identify the surgical outcomes of patients with HCC and Ex-BDTT. A total of 138 patients with Ex-BDTT who underwent hepatectomy with preservation of the extrahepatic bile duct from five large hospitals in China between January 2009 and December 2017 were included. The Cox proportional hazards model was used to analyze overall survival (OS) and recurrence-free survival (RFS). With a median follow-up of 60 months (range, 1-127.8 months), the median OS and RFS of the patients were 28.6 and 8.9 months, respectively. The 1-, 3-, and 5-year OS rates of HCC patients with Ex-BDTT were 71.7%, 41.2%, and 33.5%, respectively, and the corresponding RFS rates were 43.5%, 21.7%, and 20.0%, respectively. Multivariate analysis identified that major hepatectomy, R0 resection, and major vascular invasion were independent prognostic factors for OS and RFS. In addition, preoperative serum total bilirubin ≥ 4.2 mg/dL was an independent prognostic factor for RFS. Major hepatectomy with preservation of the extrahepatic bile duct can provide favorable long-term survival for HCC patients with Ex-BDTT.

Clinical benefits of intraoperative radiotherapy for the recurrence of centrally located hepatocellular carcinoma with microvascular invasion.

Although the efficacy and safety of intraoperative radiotherapy (IORT) in the treatment of malignant tumours, such as breast cancer, have been documented, it remains unclear whether this treatment is effective for centrally located hepatocellular carcinoma (HCC) with microvascular invasion (MVI). This study aimed to explore the efficacy and safety of IORT in the treatment of centrally located HCC with MVI. Patients with centrally located HCC, who underwent surgery between January 2016 and January 2020, were enrolled. The patient cohort was then allocated to two groups: those who underwent IORT combined with liver resection (IORT+LR); or LR alone (LR). Propensity score matching and Cox proportional hazards regression analyses were performed. The Kaplan-Meier method was used to estimate recurrence-free survival (RFS), and the log-rank test was used to determine whether RFS differed between the groups. Subgroup analysis was performed to evaluate differences in RFS and early recurrence rates in patients with different MVI grades. E-values were generated to measure the sensitivity to unmeasured confounding factors. In total, 97 patients were enrolled, 27 of whom underwent IORT+LR and 70 underwent LR alone. The 1-, 3-, and 5-year RFS rates in the IORT+LR group were 66%, 50%, and 32%, respectively, whereas those in the LR group were 54%, 37%, and 26%, respectively. After matching analysis, 23 patients were successfully matched, and RFS was found to be significantly different between the two groups (p = .04). IORT was an independent prognostic factor for RFS (hazard ratio 0.46 [95% confidence interval 0.21-0.99]). In subgroup analysis, RFS between the IORT+LR and LR groups was significantly different in patients with MVI (M1 grade) (p = .0067). The postoperative early recurrence rate was significantly reduced with IORT (p < .05). No serious complications were reported in either group following surgery. Based on E-values, the results appeared to be robust against unmeasured confounding factors. IORT+LR provided safe, feasible treatment for patients with centrally located HCC with MVI, along with an improvement in prognosis and lower early recurrence rates.

Membranous Expression of Heart Development Protein with EGF-like Domain 1 Is Associated with a Good Prognosis in Patients with Bladder Cancer.

To investigate the correlation between total protein expression of heart development protein with EGF-like domain 1 (HEG1) and clinicopathological characteristics in patients with bladder cancer (BC) after radical cystectomy (RC). We retrospectively analyzed data from 110 patients who underwent RC at Kitasato University Hospital. And we prepared an anti-HEG1 monoclonal antibody W10B9, which can detect total HEG1 protein. HEG1 protein expression in tumor cells was evaluated separately for membrane and cytoplasmic staining using immunohistochemistry. Membranous HEG1 expression was associated with absent lymphovascular invasion (p < 0.01) and low pT stage (p < 0.01). Kaplan-Meier analysis revealed that the membranous HEG1-positive group had significantly long recurrence-free survival (RFS) (p < 0.01) and cancer-specific survival (p = 0.01). Expression of membranous HEG1 was identified as an independent prognostic factor for RFS (p = 0.04). There were no significant differences between cytoplasmic HEG1 expression and clinicopathologic factors including prognosis. The expression of membranous HEG1 could serve as a favorable prognostic indicator in patients with BC treated with RC.