Independent Predictor Of Recurrence-free Survival Research Articles

Evaluation of the novel International Association for the Study of Lung Cancer grading system in adenocarcinoma with spread through air space.

The International Association for the Study of Lung Cancer (IASLC) pathology panel has proposed a new grading system for invasive lung adenocarcinoma (LADC). This study aims to validate this novel grading system for invasive LADC using propensity score matching (PSM), with a specific focus on patients exhibiting spread through air space (STAS). We retrospectively analyzed the clinicopathologic features of a large cohort of 910 non-mucinous LADCs with STAS from 2017 to 2020 and classified them according to the novel grading system. We applied PSM to adjust for potential confounders between the grading groups. Kaplan-Meier and Cox proportional hazards models were adopted for prognostic evaluation. The results showed that the IASLC grading system (grades 2 and 3) stratified well in terms of recurrence-free survival (RFS) and overall survival (OS) (P=0.02 and P=0.02, respectively) after matching, with Grade 3 being an independent predictor of RFS [hazard ratio (HR), 1.533; P=0.02] and OS (HR, 2.765; P=0.02) in multivariable models. The concordance index (C-index) and area under the curve (AUC) of the IASLC system were 0.719 and 0.754 for recurrence and 0.844 and 0.891 for death, respectively. In addition, anaplastic lymphoma kinase (ALK) fusion and tumor protein p53 (TP53) mutations were detected more frequently in grade 3 tumors, while epidermal growth factor receptor (EGFR) mutations were more prevalent in grade 2 tumors. The IASLC grade did not predict the benefit of adjuvant chemotherapy (ACT). This study suggests that the new IASLC grading system is a valuable prognostic tool for patients with STAS-positive LADC.

M2BPGi Correlated with Immunological Biomarkers and Further Stratified Recurrence Risk in Patients with Hepatocellular Carcinoma

Introduction Novel biomarkers reflecting liver fibrosis and the immune microenvironment may correlate with the risk of hepatocellular carcinoma (HCC) recurrence. This study aimed to evaluate the prognostic value of serum biomarkers in predicting HCC recurrence. Methods Serum biomarkers, including M2BPGi, IL-6, IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM-3, and LAG-3, were measured in 247 patients with HCC undergoing surgical resection. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were evaluated. The ERASL-post model and IMbrave050 criteria were used to define HCC recurrence risk groups. Results Serum M2BPGi levels significantly correlated with FIB-4 score, APRI, ALBI score, AFP, ALT, AST, IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM-3, and LAG-3 levels. M2BPGi, VEGF-A, soluble PD-1, and TIM-3 levels significantly correlated with RFS. In multivariate analysis, M2BPGi >1.5 COI (hazard ratio (HR) = 2.100, p < 0.001), tumor size >5 cm (HR = 1.859, p = 0.002), multiple tumors (HR = 2.562, p < 0.001), AFP >20 ng/mL (HR = 2.141, p < 0.001), and microvascular invasion (HR = 1.954, p = 0.004) were independent predictors of RFS. M2BPGi levels significantly stratified the recurrence risk in ERASL-post and IMbrave050 risk groups. An M2BPGi-based model could significantly discriminate RFS in the overall cohort as well as in the IMbrave050 low- and high-risk groups. M2BPGi >1.5 COI was also an independent predictor of OS after resection (HR = 2.707, p < 0.001). Conclusion Serum M2BPGi levels significantly correlated with surrogate markers of liver fibrosis, liver function, and immunology. M2BPGi is a significant predictor of HCC recurrence and survival after resection and could be incorporated into recurrence-prediction models.

Implications of pretreatment extramural venous invasion in rectal cancer patients: A population-based study.

Extramural venous invasion detected by MRI (mrEMVI) has in several expert centre studies been identified as an important prognostic factor in rectal cancer, and in guiding neoadjuvant therapy. However, population-based evidence for mrEMVI as a predictor for recurrent disease is lacking. This was a multicentre retrospective study based on the Swedish Colorectal Cancer Registry. The study period encompassed patients operated with abdominal resection for rectal cancer 2017-2021, with follow-up until January 2023. Patients diagnosed at hospitals with radiological registry data coverage <90% or with metastatic disease were excluded. Pretreatment mrEMVI constituted exposure, while recurrence-free survival was the main outcome. Distant and local recurrence, and overall survival were secondary outcomes, and pretreatment and postoperative scenarios were explored using multivariable Cox regression with multiple imputation. Hazard ratios (HRs) with 95% confidence intervals (CIs) were reported. A total of 2737 patients from 13 hospitals were eligible for analysis. Pretreatment mrEMVI was reported in 14.5% of patients, while 71.9% had negative findings and 13.6% had missing data. In the pretreatment scenario, mrEMVI was an independent predictor for worse recurrence-free survival with an adjusted HR of 1.64 (95% CI: 1.31-2.06). In the postoperative MDT setting, the influence of mrEMVI on recurrence-free survival decreased with an adjusted HR of 1.27 (95% CI: 1.00-1.61). mrEMVI at diagnosis is an independent predictor of recurrence-free survival in an unselected population of rectal cancer patients undergoing abdominal resection.

Development and validation of a nomogram to predict recurrence for clinical T1/2 clear cell renal cell carcinoma patients after nephrectomy

ObjectiveTo develop and validate a nomogram for predicting recurrence-free survival (RFS) for clinical T1/2 (cT1/2) clear cell renal cell carcinoma (ccRCC) patients after nephrectomy.MethodsClinicopathological and survival data from 1289 cT1/2 ccRCC patients treated at the Second Hospital of Tianjin Medical University between 2017 and 2020 were included. Cox regression analysis was used to identify independent risk factors in 902 and 387 ccRCC patients in the training and validation cohorts, respectively, and construct the nomogram. The performance of the nomogram was assessed through calibration plots, time-dependent receiver operating characteristic (ROC) curves, C-index (concordance-index), and decision curve analysis (DCA). Kaplan-Meier curves were used to evaluate the probability of RFS in patients with different recurrence risks.ResultsAge, tumor size, surgical approach, Fuhrman grade, and pT3a upstage were identified as independent predictors of RFS. The area under the curve (AUC) for the 3-year and 5-year RFS ROC curves were 0.791 and 0.835 in the training cohort, and 0.860 and 0.880 in the validation cohort. The DCA and calibration plots demonstrated the optimal application and excellent accuracy of the nomogram for predicting 3-year and 5-year RFS. Kaplan-Meier curves revealed significant differences in RFS among the three risk groups in both the training and validation cohorts. Clinically, the developed nomogram provides a more precise tool for risk stratification, enabling tailored postoperative management and surveillance strategies, ultimately aiming to improve patient outcomes.ConclusionsWe developed a nomogram for predicting RFS in cT1/2 ccRCC patients after nephrectomy with high accuracy. The clinical implementation of this nomogram can significantly enhance clinical decision-making, leading to improved patient outcomes and optimized resource utilization in the management of ccRCC.

Preoperative neutrophil-to-lymphocyte ratio predicts recurrence of esophageal squamous cell carcinoma after neoadjuvant triplet chemotherapy.

Neoadjuvant chemotherapy followed by esophagectomy is the standard treatment for resectable advanced esophageal squamous cell carcinoma (ESCC) in Japan. Triplet chemotherapy is the standard neoadjuvant regimen. Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) are well-known prognostic factors for esophageal cancer. However, their usefulness in patients with resectable advanced disease undergoing esophagectomy after neoadjuvant triplet chemotherapy is unknown. We examined 144 ESCC patients who underwent neoadjuvant triplet chemotherapy followed by esophagectomy between January 2015 and December 2020 to investigate the relationship between inflammatory markers and recurrence-free survival (RFS). Optimal marker cutoff values for RFS were determined using receiver operating characteristic curve analysis. Patients were divided into high and low NLR groups (NLR cutoff, 3.0). NLR was high in 61 patients and low in 83. Univariate analyses demonstrated that low NLR was significantly associated with worse RFS (p = 0.049). Multivariate analyses demonstrated that high NLR was an independent predictor of RFS (odds ratio, 1.911; 95% confidence interval, 1.098-3.327; p = 0.022). RFS significantly differed between the low and high NLR groups. RFS did not significantly differ between the patients when stratified according to the other inflammatory markers. Preoperative NLR is an easily obtained and useful predictor of RFS in patients with resectable advanced ESCC treated with neoadjuvant triplet chemotherapy followed by esophagectomy.

Abstract 7646: Evaluation of tumor immune microenvironment after neoadjuvant immunotherapy in patients with esophageal squamous cell carcinoma (ESCC): Towards a prediction for recurrence risk

Abstract Background: Despite the promising potential of neoadjuvant immune checkpoint blockade (ICB) in ESCC, postoperative recurrence remains a critical challenge. Besides pathological response, there remains no biomarkers for recurrence risk prediction after neoadjuvant ICB. Recent studies have highlighted a strong association between ICB efficacy and tumor immune microenvironment (TIME). Thus, we sought to investigate the TIME features in surgically resected tumors following neoadjuvant ICB from patients with ESCC to develop a potential way for recurrence risk prediction. Methods: This is a side study of a phase 2 NICE trial (ChiCTR1900026240) of 51 patients with resectable locally advanced ESCC who received neoadjuvant ICB plus chemotherapy followed by surgery from 2019 to 2020. TIME features of surgically resected tumors after neoadjuvant therapy were assessed by multiplex immunohistochemistry (mIHC) for immune markers (CD8, PD-L1, CD45RO, PD-1, Pan-CK, CD4, FoxP3, CD68, CD163). We first analyzed TIME features in tumors evaluated as pathological complete response (pCR) and major pathological response (MPR). Then, we divided 51 patients into a training and validation set; and machine learning was applied to identify a list of TIME features that predict recurrence-free survival (RFS) and to develop a TIME-based signature (TIS) on neoadjuvant ICB prognosis. Results: Fifty-one patients from NICE trial were used for primary analysis. A higher positive rate of CD8+ cells, CD163−CD68+ macrophages and CD8+CD45RO+ cells was observed in patients with pCR. Similarly, MPR patients exhibited a higher positive rate of CD8+ cells and CD8+CD45RO+ cells. Regarding RFS prediction, machine learning selection of TIS were identified: CD8+PD1−(cytotoxic T cells), CD4+Foxp3+ (Treg), CD8+CD45RO+ (memory T cells), and M1 macrophages (CD163−CD68+) exhibited significant predictive value. Stratifying patients into low- and high-risk groups using TIS for RFS revealed a prolonged prolonged RFS in the low-risk group (p&amp;lt;0.001; HR: 0.08, 95% CI [0.03-0.25]). Notably, when applying TIS to pCR patients, we identified a subset of high-risk pCR patients (median RFS = 8.9 months, 1- year RFS=32%) relapsed earlier than low-risk pCR patients (median RFS = not reached, 1-year RFS=100%, p&amp;lt;0.001). Multivariable Cox regression analysis demonstrated that TIS was an independent predictor for RFS as well as overall survival (both p&amp;lt;0.001). Further independent validation (ICB and non-ICB cohort) of TIS is ongoing. Conclusion: The establishment of a risk prediction model based on TIME demonstrated the potential to enhance postoperative monitoring management for ESCC patients who underwent surgery after neoadjuvant ICB. Our study provides insights into development of optimal post-immunotherapy management strategy. Citation Format: Zhichao Liu, Boyao Yu, Yuxin Yang, Cong Qi, Chang Yuan, Yang Yang, Jinzhi Wei, Sidong Chen, Yang Wang, Zhigang Li. Evaluation of tumor immune microenvironment after neoadjuvant immunotherapy in patients with esophageal squamous cell carcinoma (ESCC): Towards a prediction for recurrence risk [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 7646.

Comparison between laparoscopic liver resection and open liver resection in patients with hepatocellular carcinoma with portal vein tumor thrombosis.

Recently, the outcomes of surgical treatment for advanced hepatocellular carcinoma (HCC) have improved. However, despite the technical advancements in laparoscopic liver resection (LLR), it is still not recommended as the standard treatment for HCC with portal vein tumor thrombosis (PVTT) because of the poor oncological outcomes. This study aims to compare the clinical outcomes of open liver resection (OLR) and LLR in patients with HCC with PVTT. A total of 86 patients with PVTT confirmed in the pathological report between January 2014 and December 2018, were enrolled. Short-term, postoperative, and long-term outcomes, including recurrence-free survival and overall survival rates, were evaluated. No difference between the two groups, except for age, was detected. The median age in the laparoscopic group was significantly higher than that in the open group. Regarding the pathological features, the maximal tumor size was significantly larger in the OLR; other pathological factors did not differ. There was no significant difference between overall survival (OS) and recurrence-free survival (RFS). Vp3 PVTT (hazards ratio [HR] 6.1, 95% confidence interval [CI] 1.9-18.5), Edmondson grade IV (HR 4.7, 95% CI 1.7-12.9, p = 0.003), and intrahepatic metastasis (HR 3.9, 95% CI 2.1-7.2, p < 0.001) remained the unique independent predictors of recurrence-free survival according to a multivariate Cox proportional hazard regression analysis. Laparoscopic liver resection for the management of HCC with PVTT provides the same short- and long-term results as those of the open approach.

Adipose Tissue Quantification Improves the Prognostic Value of GLIM Criteria in Advanced Gastric Cancer Patients.

The present study investigated whether the risk of recurrence after curative surgery could be further stratified by combining the Global Leadership Initiative on Malnutrition (GLIM) criteria and changes in subcutaneous (SAT) and visceral (VAT) adipose tissue mass after surgery in patients with advanced gastric cancer (AGC). This study retrospectively analyzed 302 patients with AGC who underwent curative surgery. Based on the GLIM criteria, patients were classified into malnourished and non-malnourished groups. The cross-sectional areas of SAT and VAT were measured from preoperative and 6-month post-operative computed tomography (CT) images. Multivariate survival analyses demonstrated that GLIM-defined malnutrition (p = 0.008) and loss of VAT after surgery (p = 0.008) were independent risk factors for recurrence-free survival (RFS). Evaluation of the prognostic value of combining the two independent predictors showed that malnourished patients with a marked loss of VAT had the worst 5-year RFS rate of 35.2% (p < 0.001). Preoperative GLIM-defined malnutrition and a loss of VAT during the first 6 months after surgery were independent predictors for RFS in patients with AGC. Changes in the VAT area after surgery could further enhance the prognostic value of the GLIM criteria for predicting the risk of gastric cancer recurrence.

232P Tumor spread through air spaces is an independent predictor of recurrence-free survival in patients with resected pulmonary lymphoepithelial carcinoma

232P Tumor spread through air spaces is an independent predictor of recurrence-free survival in patients with resected pulmonary lymphoepithelial carcinoma

Prognostic Significance of Sarcopenia and Systemic Inflammatory Markers in Biliary Tract Cancer: A Retrospective Cohort Study.

To evaluate the prognostic significance of sarcopenia and systemic inflammatory markers in patients with surgically resected biliary tract cancer (BTC). Between July 2010 and December 2022, 146 patients were recruited. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used to calculate the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine prognostic factors for overall survival (OS) and recurrence-free survival (RFS). P < 0.05 was considered statistically significant. Sixty-four patients had sarcopenia. Sarcopenia was associated with body mass index (< 22 kg/m2), lymph node metastasis, and low PNI (< 42). R1/R2 resection (P = 0.02), sarcopenia (P < 0.001), lymph node metastasis (P = 0.007), intrahepatic cholangiocarcinoma (P < 0.001), and low PNI (P = 0.01) were independent predictors of OS, while male sex (P = 0.04), R1/R2 resection (P < 0.001), lymph node metastasis (P = 0.005), intrahepatic cholangiocarcinoma (P < 0.001), tumor differentiation (other than well; P = 0.003), and low PNI (P = 0.03) were independent predictors of RFS. Patients were stratified into no sarcopenia and high PNI (≥ 42; A), sarcopenia or low PNI (B), and sarcopenia and low PNI (C) groups. Group C had worse OS than the other two groups (P < 0.001 and P = 0.02, respectively). Sarcopenia is associated with the PNI. Sarcopenia and the PNI are independent prognostic factors among patients with resected BTC. Sarcopenia may have better prognostic value when combined with the PNI.

Impact of adjuvant chemotherapy on patients with stage IB non-small cell lung cancer with visceral pleural invasion.

Adjuvant chemotherapy has reduced the risk of recurrence and death in stage IB non-small cell lung cancer (NSCLC) with high-risk factors; however, the impact of visceral pleural invasion (VPI) on outcomes in stage IB NSCLC treated with adjuvant chemotherapy remains controversial. The aim of this study was to explore the clinical and prognostic significance of adjuvant chemotherapy for stage IB (1-4 cm) NSCLC with VPI. This retrospective study included 251 patients admitted between January 2008 and May 2018 from four hospitals who underwent complete resection for Tumor-Node-Metastasis (TNM) 8th edition stage IB NSCLC with VPI. The relationship between adjuvant chemotherapy and overall survival (OS) or recurrence-free survival (RFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards model. Of 251 patients with stage IB NSCLC with VPI, 122 (48.6%) received adjuvant chemotherapy after surgical resection and 129 (51.4%) were placed under observation. Multivariable analysis showed that adjuvant chemotherapy was an independent predictor of RFS [adjusted hazard ratio (aHR), 0.57; 95% confidence interval (CI): 0.33-0.96; P=0.036]. A micropapillary pattern (aHR, 2.46; 95% CI: 1.33-4.55; P=0.004) and lymphovascular invasion (aHR, 2.86; 95% CI: 1.49-5.48; P=0.002) were associated with a higher risk of recurrence. Multivariable analysis also showed that adjuvant chemotherapy was an independent predictor of OS (aHR, 0.22; 95% CI: 0.09-0.58; P=0.002). In a subgroup analysis of patients with a tumor size of 1-3 cm, adjuvant chemotherapy was associated with improved RFS and OS, and this association was maintained even when patients with VPI had additional risk factors. Our study shows that adjuvant chemotherapy is appropriate for patients with stage IB (1-4 cm) NSCLC with VPI, and even those with smaller tumors (1-3 cm).

Prognostic Impact of Preoperative Thrombocytosis on Recurrence-Free Survival in Patients with Upper Tract Urothelial Carcinoma.

The aim of this work was to evaluate the prognostic potential of preoperative thrombocytosis for recurrence-free survival (RFS) and cancer-specific survival (CSS) among patients subjected to radical nephroureterectomy (RNU) due to UTUC. Analytical cohort was composed of a single-center series of 405 patients treated between January 1999 and December 2020. Thrombocytosis was defined as a platelet count exceeding the threshold value of 400 × 109 per L. Along with the Kaplan-Meier survival probability, Cox proportional hazard regression models were used. Preoperative thrombocytosis confirmed in 71 patients (17.5%) was significantly associated with the higher pathological tumor stage, lymph node metastasis, prior bladder cancer diagnosis, and preoperative anemia. With a median post-surgical follow-up period of 33.5 months, 125 patients (30.9%) experienced disease recurrence. The recurrence rate among patients with normal platelet levels was 13.6%, compared with 22.2% in those with preoperative thrombocytosis (p < 0.03). The 5-year RFS estimates reached 36.6% in the thrombocytosis-confirmed group. Multivariate analysis implied that preoperative thrombocytosis was a significant independent prognosticator of both poor RFS (HR 2.22, 95% CI 1.14-4.31, p = 0.02) and CSS (HR 2.48, 95% CI 1.14-3.09, p = 0.01). Patients with a clinically significant elevation of platelet count prior to RNU were more likely to have UTUC with advanced tumor stages and lymph node metastases. Preoperative thrombocytosis was an independent predictor of RFS and CSS in patients who underwent radical nephroureterectomy. Furthermore, preoperative thrombocytosis may complement and refine UTUC clinical prediction algorithms as an independent indicator of adverse survival outcomes.

Development of a ferroptosis-based molecular markers for predicting RFS in prostate cancer patients

The goal of this study was to develop a ferroptosis-based molecular signature that can predict recurrence-free survival (RFS) in patients with prostate cancer (PCa). In this study, we obtained ferroptosis-related genes (FRGs) in FerrDb database and clinical transcriptome data in TCGA database and GEO database. Consensus cluster analysis was used to identify three molecular markers of ferroptosis in PCa with differential expression of 40 FRGs, including PD-L1 expression levels. We conducted a new ferroptosis-related signature for PCa RFS using four FRGs identified through univariate and multivariate Cox regression analyses. The signature was validated in the training, testing, and validation cohorts, and it demonstrated remarkable results in the area under the time-dependent receiver operating characteristic (ROC) curve of 0.757, 0.715, and 0.732, respectively. Additionally, we observed that younger patients, those with stage T III and stage T IV, stage N0, cluster 1, and cluster 2 PCa were more accurately predicted by the signature as independent predictors of RFS. DU-145 and RWPE-1 cells were successfully analyzed by qRT-PCR and Western blot for ASNS, GPT2, RRM2, and NFE2L2. In summary, we developed a novel ferroptosis-based signature for RFS in PC, utilizing four FRGs identified through univariate and multivariate Cox regression analyses. This signature was rigorously validated across training, testing, and validation cohorts, demonstrating exceptional performance as evidenced by its ROC curves. Notably, our findings indicate that this signature is particularly effective as an independent predictor of RFS in younger patients or those with stage T III and T IV, stage N0, and in clusters 1 and 2. Finally, we confirmed the expression of these four FRGs in DU-145 and RWPE-1 cell lines.

Optimal interval timing between transurethral resection of bladder tumors and Bacillus Calmette-Guerin perfusion.

There is no consensus regarding the best interval time between transurethral resection of a bladder tumor and Bacillus Calmette-Guerin (BCG) perfusion. This study was to explore whether the interval time has an impact on the prognosis and adverse effects. We retrospectively reviewed the clinical data of patients who received BCG intravesical perfusion at Sun Yat-sen University Cancer Center (SYSUCC) from September 2015 to October 2021. Recurrence-free survival (RFS) and progression-free survival were the primary endpoints. Cox regression was used to explore independent predictors. The association between interval time and adverse effect grade was detected by logistic regression. Propensity score matching (PSM) was performed. A total of 403 patients were enrolled, the median interval time was 24 days (6-163 days), and the follow-up was 28 months (7-82 months). Eighty-eight (20.9%) patients relapsed, and 40 patients (10.0%) suffered progression. The multivariate Cox regression analysis confirmed that interval time was an independent predictor of RFS (p = 0.017). Notably, when the interval time was less than or equal to 26 days, there was a trend toward better RFS, PSM resulted in 65 matched pairs in each group, and Kaplan-Meier analysis showed that there was a significant difference in RFS between groups (p = 0.009). The logistic regression analysis showed that there was no correlation between interval time and adverse effects and their grades (p > 0.05). We considered that the first BCG perfusion could be performed within 2-4 weeks after surgery.

Risk stratification for overall survival and recurrence-free survival after R0 resection for solitary intrahepatic mass-forming cholangiocarcinoma based on preoperative MRI and clinical features

PurposeThis study aimed to establish two nomograms for predicting overall survival (OS) and recurrence-free survival (RFS) in patients with solitary intrahepatic mass-forming cholangiocarcinoma (IMCC) based on preoperative magnetic resonance imaging (MRI) features. MethodsThis retrospective study included 120 consecutive patients who were diagnosed with solitary IMCC. Preoperative MRI and clinical features were collected. Based on the univariate and multivariate Cox regression analyses, two nomograms were constructed to predict OS and RFS, respectively. The effective performance of the nomograms was evaluated using concordance index (C-index). The prognostic stratification systems for OS and RFS were developed and used to classify patients into high- and low-risk groups. ResultsSuspicious lymph nodes, arterial phase (AP) enhancement patterns, and bile duct dilatation were independent predictors of OS, while suspicious lymph nodes, AP enhancement patterns, and necrosis were independent predictors of RFS. The nomograms achieved the C-index values of 0.705/0.710 for OS and 0.721/0.759 for RFS in the development/validation cohorts, which were significantly higher than those of the T and TNM stages (P < 0.05). Patients were stratified into high- and low-risk groups, the 1-year OS and RFS rates of high-risk patients were poorer than those of patients with low-risk in the development cohort (OS: 93.5% vs 76.3%, P < 0.001; RFS: 74.5% vs 22.4%, P < 0.001). Similar results were observed in the validation cohort. ConclusionsTwo nomograms were constructed based on preoperative MRI features in patients with solitary IMCC for predicting the OS and RFS and facilitate further prognostic stratification.

Clinicopathological characteristics, surgical treatments, and oncological outcomes of localized primary unifocal urothelial carcinoma involving the ureterovesical junction.

To investigate clinicopathological characteristics, surgical treatments, and oncological outcomes of patients with localized primary unifocal urothelial carcinoma involving the ureterovesical junction (UC-UVJ). Localized primary unifocal UC-UVJ cases in patients admitted to our hospital from March 2013 to August 2021 were reviewed. Clinicopathological parameters, perioperative data, and oncological outcomes were compared between patients grouped by tumor location and surgical treatment. A total of 130 patients with localized primary unifocal UC-UVJ were enrolled in this study. These included 72 cases of bladder cancer (BC) involving the ureteral orifice, and 58 cases of upper urinary tract urothelial carcinoma (UTUC) involving the intramural ureter. The proportion of male patients, hydronephrosis, flank pain/abdominal pain, and tumor size differed significantly between the BC and UTUC groups (all P < 0.05). During the median follow-up period of 32.9months, 49 cases (37.7%) recurred and 29 (22.3%) died from urothelial carcinoma (UC), though no statistical difference in recurrence (P = 0.436) or cancer-specific mortality (P = 0.653) was observed between the BC and UTUC groups. Cox proportional hazards regression analysis identified age, tumor grade, and lymphovascular invasion (LVI) as independent predictors of cancer-specific survival (CSS), and sex, T stage, tumor grade, and LVI as independent predictors of recurrence-free survival (RFS). Owing to positional properties, patients with localized primary unifocal UC-UVJ exhibited significant heterogeneity, leading to varied treatment strategies. No statistically significant differences in CSS or RFS were observed between the BC and UTUC groups. Furthermore, age, sex, T stage, tumor grade, and LVI should be carefully considered in clinical practice because of their associations with CSS and RFS.

Residual circulating tumor DNA after adjuvant chemotherapy effectively predicts recurrence of stage II-III gastric cancer.

Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context. From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer-related genes. The plasma was defined as ctDNA-positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors. Compared with ctDNA-negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37-5.48; P = 0.003], while patients with positive post-ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08-72.96; P < 0.001). Multivariate analyses indicated that both postoperative and post-ACT ctDNA positivity were independent predictors of recurrence-free survival (RFS). Moreover, post-ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C-index (0.78; 95% CI = 0.71-0.84) than the model without ctDNA (0.71; 95% CI = 0.64-0.79; P = 0.009). Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue-based and circulating tumor features could achieve better risk prediction.

Plasma EBV DNA in Nasopharyngeal Cancer (NPC) Treated with Definitive Radiotherapy (RT)

EBV DNA has well-studied roles in NPC including early detection and surveillance. There are limited North American data on EBV DNA testing. Our center has used EBV DNA testing since 2010. We hypothesized: (1) higher first post-RT EBV DNA level is associated with worse prognosis, and (2) surveillance EBV DNA is specific for recurrence at a low detection threshold. We retrospectively reviewed all patients with non-metastatic (TNM-7 stage I-IVB) NPC treated with definitive RT/chemoRT (CRT) ± adjuvant chemotherapy (AC) between 2010-2017. EBV DNA was assayed by quantitative PCR in a CAP/CLIA-certified laboratory and reported in copies/mL of plasma. Pre-RT is defined as 0-90 days before the first RT fraction and post-RT within one year after RT. We report log odds ratios (LOR) from a linear model of T- and N-category with log-adjusted EBV DNA as the response variable. Survival outcomes were analyzed with log-rank tests and Cox multivariate analyses (MVA) adjusted for age, stage, and treatment, reporting hazard ratios (HR). A total of 95% confidence intervals of LOR and HR are reported. The detection threshold that maximized the F1 accuracy score was considered optimal. Of 271 patients in the study window, 179 had pre-RT +/- post-RT EBV DNA testing. Six received RT, 43 CRT, and 130 CRT+AC. With 7-yr median follow-up, 37 recurred and 37 died. Detectable pre-RT EBV DNA was found in 154 (86%) with a median of 928 copies/mL (range: 1-239214). EBV DNA level correlated with higher N category (LOR: 0.28, 0.15-0.42, p<0.001), but not T category (0.04, -0.06-0.13, p = 0.5). Above-median pre-RT EBV DNA was associated with worse recurrence-free survival (RFS) by log-rank test (p = 0.016) and Cox MVA (HR: 2.2, 1.1-4.8, p = 0.03) along with N category, age, and no AC. Post-RT EBV DNA was available in 99 patients at a median of 54 days. RFS, progression-free survival (PFS), and overall survival (OS) were worse in patients with detectable post-RT EBV DNA (Table). RFS and PFS drop further to 20% if EBV DNA was detectable after the full treatment (RT±AC, n = 71). In Cox MVA, post-RT EBV DNA remained independently prognostic (Table). EBV DNA was performed within 30 days of recurrence in 30 patients, and 24 were detectable (80% sensitivity). Conversely, of 152 patients without recurrence and at least 3-yr follow-up, 95 had post-RT EBV DNA testing and 84 were undetectable (88% specificity). An EBV DNA threshold of 31 copies maximized F1 accuracy metric, yielding 74% sensitivity and 97% specificity. Pre-RT EBV DNA is prognostic and associated with higher N-category. Post-RT EBV DNA is a strong, independent predictor of RFS, PFS, and OS; 31 copies/mL may be a useful threshold to detect recurrence.

Overexpressed transferrin receptor implied poor prognosis and relapse in gastrointestinal stromal tumors.

Ferroptosis, as a novel-induced programmed cell death, plays critical roles in the pathogenesis of cancers. However, the promising biomarkers of ferroptosis in gastrointestinal stromal tumor (GIST) remain to be elucidated. Herein, the expression of ferroptosis-related genes was analyzed in GIST. Among the 64 ferroptosis-related genes, transferrin receptor (TFRC) expression presented a remarkable upregulation in high-risk patients through Gene Expression Omnibus (GEO) dataset analysis, as well as its significant change after imatinib was treated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of TFRC-relevant genes revealed that TFRC expression was closely associated with cell growth pathways and metabolism-related pathways. Furthermore, patients at high risk of recurrence were more likely to exhibit high TFRC expression by immunohistochemistry. Additionally, high TFRC expression indicated an undesirable state of patient relapse, which could serve as a powerful significant independent predictor of recurrence-free survival (RFS). In summary, we systematically summarize the expression characteristics and clinical relevance of TFRC and show that TFRC can be used as a prognostic factor, which can be considered a potential therapeutic target in GIST.

Prognostic significance of the preoperative platelet-lymphocyte ratio in nonmetastatic renal cell carcinoma: cross-sectional study.

The objective of our study was to evaluate the prognostic significance of the PLR in patients with nonmetastatic RCC. The authors performed a retrospective analysis of patients with nonmetastatic RCC who were operated between 2004 and 2020. Five years recurrence-free survival and metastasis-free survival were calculated. The prognostic significance of the preoperative PLR was assessed. The Kaplan-Meier method was utilized to graphically display survivor functions. Univariate and multivariate Cox's proportional hazards regression models were utilized to analyze the association between PLR and oncological outcomes. Differences were considered significant if P<0.05. Two hundred and two patients were included. The mean follow-up was 56.8±3 months. Patients with a higher PLR had larger tumors (P=0.02), higher ASA score (P=0.001), symptomatic forms (P=0.01), and more frequent tumor necrosis (P=0.02). Recurrence-free survival and metastasis-free survival rates were significantly lower in patients with high PLR than in those with low ratios (each P<0.005). Multivariate analysis identified PLR as an independent predictor of recurrence-free survival (P=0.002) and metastasis-free survival (P<0.001). A higher PLR was associated with aggressive renal cancer. In addition, the PLR was a significant prognostic factor for both recurrence-free survival and metastasis-free survival in patients with nonmetastatic RCC.