Independent Predictor Of Relapse-free Survival Research Articles

PD-L1 expression and tumor-infiltrating lymphocytes: Correlations and prognostic values in Chinese triple-negative breast cancer patients with different molecular subtyping

ObjectiveTo investigate the correlation between programmed death ligand-1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) and evaluate the prognostic value of PD-L1 and TILs in Chinese triple-negative breast cancer (TNBC) patients with different molecular subtype MethodsThis retrospective study was conducted at 2020. Specifically, the pre-chemotherapy clinical data and non-stained tissue blocks of 465 TNBC patients visited the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014 were collected, with their blocks sliced and stained using PD-L1(SP142), and the outcome of subsequent chemotherapy obtained in 2020. The relapse-free survival (RFS) of the study population was calculated. The baseline PD-L1 expression status correlations with TILs and molecular subtypes were assessed using Spearman’s rank correlation analysis and the Kruskal-Wallis test. Kaplan-Meier survival analyses were undertaken to evaluate the prognosis value of TILs and PD-L1 expression. ResultsPD-L1 expression status on IC was moderately and positively correlated with stromal tumor-infiltrating lymphocytes (sTILs) (rs = 0.502, P <0.001) and iTILs (rs = 0.410, P < 0.001), respectively. PD-L1 expression status and TILs showed significant differences among molecular subtypes (P < 0.001), with the highest proportion of PD-L1+ and high TILs patients observed in the immunomodulatory (IM) subtype. TILs were significantly associated with RFS. Moreover, sTILs could act as an independent predictor of RFS (RR 0.953, 95 % CI 0.920 ∼ 0.987, P = 0.007), while PD-L1 expression status did not show the same prognostic significance. ConclusionsThe incorporation of pre-treatment TILs and PD-L1 expression status as valuable tools for optimizing patient selection for immunotherapy and managing the risks associated with chemotherapy in Chinese TNBC patients. Data availabilityThe data sets generated and analyzed during the current study are available from the corresponding author.

A 69 long noncoding RNA signature predicts relapse and acts as independent prognostic factor in pediatric AML

AbstractRisk stratification using genetics and minimal residual disease has allowed for an increase in the cure rates of pediatric acute myeloid leukemia (pedAML) to up to 70% in contemporary protocols. Nevertheless, ∼30% of patients still experience relapse, indicating a need to optimize stratification strategies. Recently, long noncoding RNA (lncRNA) expression has been shown to hold prognostic power in multiple cancer types. Here, we aimed at refining relapse prediction in pedAML using lncRNA expression. We built a relapse–related lncRNA prognostic signature, named AMLlnc69, using 871 transcriptomes of patients with pedAML obtained from the Therapeutically Applicable Research to Generate Effective Treatments repository. We identified a 69 lncRNA signature AMLlnc69 that is highly predictive of relapse risk (c-index = 0.73), with area under the receiver operating characteristic curve (AUC) values for predicting the 1-, 2-, and 3-year relapse-free survival (RFS) of 0.78, 0.77, and 0.77, respectively. The internal validation using a bootstrap method (resampling times = 1000) resulted in a c-index of 0.72 and AUC values for predicting the 1-, 2-, and 3-year RFS of 0.77, 0.76, and 0.76, respectively. Through a Cox regression analysis, AMLlnc69, nucleophosmin mutation, and white blood cell at diagnosis were identified as independent predictors of RFS. Finally, a nomogram was build using these 2 parameters, showing a c-index of 0.80 and 0.71 after bootstrapping (n = 1000). In conclusion, the identified AMLlnc69 will, after prospective validation, add important information to guide the management of patients with pedAML. The nomogram is a promising tool for easy stratification of patients into a novel scheme of relapse-risk groups.

A 46 Long Non-Coding RNAs Expression Signature Accurately Predicts Relapse and Acts As an Independent Prognostic Factor in Pediatric Acute Myeloid Leukemia

Risk stratification using cytogenetics, mutations and minimal residual disease (MRD) has allowed to increase the cure rates of pediatric acute myeloid leukemia (AML), reaching now up to 70% in contemporary protocols. Nevertheless, approximately 30% of patients still experience relapse, indicating that there is a need to optimize stratification strategies. Recently, long non-coding RNA (lncRNA) expression has been shown to hold prognostic power in multiple cancer types. Here, we built a 46 relapse-related lncRNAs prognostic signature, named AML lnc46, using 790 pediatric acute myeloid leukemia transcriptomes obtained from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) repository. Bootstrap validation (bootstrap resampling times = 1000) was used for internal validation and showed that the signature performed good in predicting the 1-, 2-, and 3-year relapse-free survival (RFS), with an area under the curve of 0.825, 0.824, and 0.822, respectively. Moreover, external validation using the TARGET repository validated the efficiency of the signature. Most importantly, we demonstrate that AML lnc46 not only is an independent predictor of RFS, but also identifies patients who were assigned a different risk-group by currently-used classification methods. In conclusion, the identified AML lnc46 might, after further prospective validation, provide additional information to guide management of pediatric AML patients. Figure 1. (A) Kaplan-Meier survival curve of relapse-free survival of high-and-low risk AML lnc46 pediatric AML patients, (B) Univariate and multivariate independent Cox regression analyses of known clinical and molecular characteristics and the AML lnc46 signature.

Serum circRNA_100199 is a Prognostic Biomarker in Acute Myeloid Leukemia.

An aberrant level of serum microRNA expression has been demonstrated to be a prognostic marker for acute myeloid leukemia (AML). The therapeutic relevance of serum circRNA 100199 remained unknown, however. This research aimed to investigate the probable prognostic significance of serum circRNA_100199 for AML. This study included a total of 200 participants consisting of 114 AML-diagnosed patients and 86 healthy people. Blood samples were taken, and the level of circRNA_100199 in the serum was measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to explore its potential clinical significance. Our study demonstrated that circRNA_100199 expression in the serum was substantially higher in AML subjects than in healthy persons. This increase in serum circRNA_100199 levels was particularly noticeable in M4/M5 subtype AML patients, and those with poor cytogenetic risk or higher white blood cell counts. Using receiver operating characteristic (ROC) analysis, AML cases were effectively differentiated from healthy persons based on the level of serum circRNA_100199. Furthermore, it was found that high serum circRNA_100199 expression was strongly linked with shorter survival times and more severe clinical features. Our study also confirmed that high serum circRNA_100199 expression was an independent predictor of relapse-free survival (RFS) and overall survival (OS) in AML patients. Interestingly, the serum expression level of circRNA_100199 was significantly reduced following treatment, and its levels were substantially lower in AML patients who achieved complete remission (CR) than those who did not. Overall, these findings suggest that serum circRNA_100199 has the potential to be a favorable prognostic biomarker for AML.

Lymph node ratio and hematological parameters predict relapse-free survival in patients with high grade rectal neuroendocrine neoplasms after radical resection: a multicenter prognostic study

BackgroundThe prognostic nutritional index (PNI), alkaline phosphatase (ALP), and lymph node ratio (LNR) are reportedly related to prognosis. The aim of this study was to elucidate the clinical importance of the LNR and hematological parameters in patients with high grade rectal neuroendocrine neoplasms (HG-RNENs) who were undergoing radical resection.MethodsWe reviewed the medical records of patients with HG-RNENs from 17 large-scale medical centers in China (January 1, 2010–April 30, 2022). A nomogram was constructed by using a proportional hazard model. Bootstrap method was used to draw calibration plots to validate the reproducibility of the model. Concordance index (C-Index), decision curve analysis (DCA), and time-dependent area under the receiver operating characteristic curve (TD-AUC) analysis were used to compare the prognostic predictive power of the new model with American Joint Committee on Cancer (AJCC) TNM staging and European Neuroendocrine Tumor Society (ENETS) TNM staging.ResultsA total of 85 patients with HG-RNENs were enrolled in this study. In the 45 patients with HG-RNENs who underwent radical resection, PNI ≤ 49.13 (HR: 3.997, 95% CI: 1.379–11.581, P = 0.011), ALP > 100.0 U/L (HR: 3.051, 95% CI: 1.011–9.205, P = 0.048), and LNR > 0.40 (HR: 6.639, 95% CI: 2.224–19.817, P = 0.0007) were independent predictors of relapse-free survival. The calibration plots suggested that the nomogram constructed based on the three aforementioned factors had good reproducibility. The novel nomogram revealed a C-index superior to AJCC TNM staging (0.782 vs 0.712) and ENETS TNM staging (0.782 vs 0.657). Also, the new model performed better compared to AJCC TNM staging and ENETS TNM staging in DCA and TD-AUC analyses.ConclusionsLNR, ALP, and PNI were independent prognostic factors in patients with HG-RNENs after radical resection, and the combined indicator had better predictive efficacy compared with AJCC TNM staging and ENETS TNM staging.

High expression of embryonic stem cell marker SSEA3 confers poor prognosis and promotes epithelial mesenchymal transition in hepatocellular carcinoma

BackgroundMalignant cells may arise from dedifferentiation of mature cells and acquire features of the progenitor cells. Definitive endoderm from which liver is derived, expresses glycosphingolipids (GSLs) such as stage-specific embryonic antigen 3 (SSEA3), Globo H, and stage-specific embryonic antigen 4 (SSEA4). Herein, we evaluated the potential prognosis value of the three GSLs and biological functions of SSEA3 in hepatocellular carcinoma (HCC). MethodsThe expression of SSEA3, Globo H, and SSEA4 in tumor tissues obtained from 328 patients with resectable HCC was examined by immunohistochemistry staining. Epithelial mesenchymal transition (EMT) and their related genes were analyzed by transwell assay and qRT-PCR, respectively. ResultsKaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with higher expression of SSEA3 (p < 0.001), Globo H (p < 0.001), and SSEA4 (p = 0.005) and worse overall survival (OS) for those with high expression of either SSEA3 (p < 0.001) or SSEA4 (p = 0.01). Furthermore, multivariable Cox regression analysis identified the SSEA3 as an independent predictor for RFS (HR: 2.68, 95% CI: 1.93–3.72, p < 0.001) and OS (HR: 2.99, 95% CI: 1.81–4.96, p < 0.001) in HCC. Additionally, SSEA3-ceramide enhanced the EMT of HCC cells, as reflected by its ability to increase migration, invasion and upregulate the expression of CDH2, vimentin, fibronectin, and MMP2, along with ZEB1. Moreover, ZEB1 silencing abrogated the EMT-enhancing effects of SSEA3-ceramide. ConclusionsHigher expression of SSEA3 was an independent predictor for RFS and OS in HCC and promoted EMT of HCC via upregulation of ZEB1.

Genome-wide methylation profiling identifies a novel gene signature for patients with synchronous colorectal cancer.

There are no robust tools for the diagnosis of synchronous colorectal cancer (SyCRC). Herein, we developed the first methylation signature to identify and characterise patients with SyCRC. For biomarker discovery, we analysed the genome-wide methylation profiles of 16 SyCRC and 18 solitary colorectal cancer (SoCRC) specimens. We thereafter established a methylation signature risk-scoring model to identify SyCRC in an independent cohort of 38 SyCRC and 42 SoCRC patients. In addition, we evaluated the prognostic value of the identified methylation profile. We identified six differentially methylated CpG probes/sites that distinguished SyCRC from SoCRC. In the validation cohort, we developed a methylation panel that identified patients with SyCRC from not only larger tumour (AUC = 0.91) but also the paired remaining tumour (AUC = 0.93). Moreover, high risk scores of our panel were associated with the development of metachronous CRC among patients with SyCRC (AUC = 0.87) and emerged as an independent predictor for relapse-free survival (hazard ratio = 2.72; 95% CI = 1.12-6.61). Furthermore, the risk stratification model which combined with clinical risk factors was a diagnostic predictor of recurrence (AUC = 0.90). Our novel six-gene methylation panel robustly identifies patients with SyCRC, which has the clinical potential to improve the diagnosis and management of patients with CRC.

Colon inflammatory index as a useful prognostic marker after R0 resection in patients with colorectal cancer liver metastasis.

BackgroundAlthough R0 resection for colorectal cancer liver metastasis (CRLM) is a promising treatment with improved prognosis, the recurrence rate is still high. No prognostic markers have been reported after resection of CRLM. In this study, we investigated the association between inflammation-based score and prognosis after R0 resection in patients with CRLM.MethodsWe retrospectively investigated 90 patients who underwent R0 resection for CRLM between 2008 and 2018. We calculated colon inflammatory index (CII) (CII0, low risk; CII1, intermediate risk; and CII2, high risk), modified Glasgow prognostic score, prognostic nutritional index, and CRP-to-albumin ratio; and retrospectively assessed the relationship between these scores, the clinicopathological features, and prognosis.ResultsThe median follow-up period was 44 months (range, 2–101 months). Five-year relapse-free survival (RFS) (CII2; 12.5%, CII1; 14.5%, CII0; 42.9%) and 5-year overall survival (OS) (CII2; 32.4%, CII1; 25.4%, CII0; 57.7%) were significantly lower in the high CII groups (CII1–2) compared with the low CII group (CII0) (p = 0.021 and p = 0.006, respectively). CEA level was significantly higher in the high CII group than the low CII group (12.4 vs 7.3, p = 0.004). Multivariate analysis showed CII score as an independent predictor of RFS (hazard ratio 2.128, 95%CI 1.147–3.430, p = 0.015) and OS (hazard ratio 2.639, 95%CI 1.331–5.323, p = 0.005).ConclusionCII shows promise as a prognostic marker after R0 liver resection in patients with CRLM.

Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma.

Background: B7-H3, also known as CD276, an important immune checkpoint member of the B7-CD28 family, is confirmed as a promising target after PD-L1 in clinical trials. Although the overexpression of B7-H3 has been associated with invasive metastatic potential and poor prognosis in multiple types of cancer, nothing is known regarding the expression profiles of B7-H3 in papillary thyroid carcinoma (PTC). In this study, we carried out a large-scale analysis of B7-H3 expression in PTC patients and evaluated the potential clinical significance of B7-H3. Methods: In total, data from 1,210 samples, including 867 cases from TCGA and four GEO datasets, were collected for B7-H3–related transcriptome analyses, and 343 postoperative, whole-tumor sections were collected from patients with PTC at our institute for B7-H3–specific immunohistochemistry (IHC) staining. The statistical analysis was primarily accomplished using the R project for statistical computing. Results: B7-H3 positivity was found in 84.8% of PTC patients (291/343), and the mRNA and protein expression levels of B7-H3 in PTC were markedly higher than those of para-tumor tissues (p < 0.001), demonstrating that B7-H3 can serve as a potential diagnostic biomarker for PTC. The significant upregulation of B7-H3 in PTC is caused by distinct patterns of CNVs and CpG DNA methylation. Functional enrichment analysis confirmed that high B7-H3 expression was significantly associated with specific immune features and angiogenesis. High B7-H3 protein expression was associated with tumor size (p = 0.022), extrathyroidal extension (ETE) (p = 0.003), and lymph node metastasis (LNM) (p < 0.001). More importantly, multivariate analysis confirmed that B7-H3 was an independent predictor of relapse-free survival (RFS) (p < 0.05). In the subgroup analysis, positive B7-H3 staining was associated with worse RFS in patients with primary tumor size ≥2 cm (p < 0.05), age ≥55 years (p < 0.05), LNM (p = 0.07), multifocality (p < 0.05), and ETE (p < 0.05). In addition, Circos plots indicated that B7-H3 was significantly associated with other immune checkpoints in the B7-CD28 family. Conclusion: This is the first comprehensive study to elucidate the expression profile of B7-H3 in PTC. Our observations revealed that B7-H3 is a novel independent biomarker for predicting LNM and disease recurrence for PTC patients, and it thus may serve as an indicator that could be used to improve risk-adapted therapeutic strategies and a novel target for immunotherapy strategies for patients who undergo an aggressive disease course.

The influence of familial pancreatic cancer on postoperative outcome in pancreatic cancer: relevance to adjuvant chemotherapy.

Familial pancreatic cancer (FPC) is defined as a family in which at least two first-degree relatives have pancreatic cancer (PC). The prognostic significance of PC in an FPC family after surgery is not fully understood. This was a retrospective study of 427 patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2008 and December 2016. PC patients who also had at least one first-degree relative with PC were defined as FPC patients. The associations between recurrence and clinicopathological characteristics were analyzed for both FPC and non-FPC patients. FPC patients accounted for 31 of the 427 (7.3%) patients. Recurrence occurred in 72.1% of the total cohort and in 87.1% of the 31 FPC patients. Multivariate analysis showed that being an FPC patient was an independent predictor for relapse-free survival (RFS) (hazard ratio [HR] 1.52, P = 0.038). Although univariate analysis revealed that being an FPC patient was significantly associated with poorer overall survival (OS) (P < 0.001), multivariate analysis showed that being an FPC patient was not an independent predictor for OS (P = 0.164). Dichotomization of the 427 patients into those who received (n = 317: 17 FPC and 300 non-FPC patients) and did not receive (n = 110: 14 FPC and 96 non-FPC patients) adjuvant chemotherapy revealed that being an FPC patient was an independent predictor for RFS (HR 2.50, P < 0.001) and OS (HR 2.30, P = 0.003) only for patients who received adjuvant chemotherapy. This study has shown that being an FPC patient is a significant prognostic indicator for PC patients who undergo resection and receive adjuvant chemotherapy.

SLC25A11 serves as a novel prognostic biomarker in liver cancer

Liver cancer is a disease with high mortality; it is often diagnosed at intermediate and advanced stages and has a high recurrence rate. ROS restriction and adequate energy supply play significant roles in liver cancer. SLC25A11, a member of the malate-aspartate shuttle (MAS), regulates electroneutral exchange between 2-oxoglutarate and other dicarboxylates. It transports glutathione (GSH) from the cytoplasm into mitochondria to maintain GSH levels to limit ROS production. Moreover, SLC25A11 is essential for ATP generation in cancers as it regulates NADH transportation from the cytoplasm to mitochondria. The purpose of this research was to investigate the prognostic value of SLC25A11 in liver cancer. The Cancer Genome Atlas database was used to analyze the levels of SLC25A11 in liver cancer. Fisher’s exact and chi-square tests were used to evaluate the relationship between SLC25A11 expression and clinical characteristics. Finally, we explored the value of SLC25A11 in prognosis by Cox analysis and Kaplan-Meier curves. Our results revealed that SLC25A11 was downregulated in liver cancer compared to normal controls. Low expression of SLC25A11 was associated with clinical stage, vital status, histologic grade, overall survival (OS) and relapse-free survival (RFS). Liver cancer patients with low SLC25A11 expression had shorter OS and RFS than patients with high SLC25A11 expression. Multivariate analysis showed that the expression of SLC25A11 was an independent predictor of RFS and OS. In conclusion, this study identified that SLC25A11 serves as a new prognostic marker for liver cancer.

A Quantitative Centrosomal Amplification Score Predicts Local Recurrence of Ductal Carcinoma In Situ.

The purpose of this study is to predict risk of local recurrence (LR) in ductal carcinoma in situ (DCIS) with a new visualization and quantification approach using centrosome amplification (CA), a cancer cell-specific trait widely associated with aggressiveness. This first-of-its-kind methodology evaluates the severity and frequency of numerical and structural CA present within DCIS and assigns a quantitative centrosomal amplification score (CAS) to each sample. Analyses were performed in a discovery cohort (DC, n = 133) and a validation cohort (VC, n = 119). DCIS cases with LR exhibited significantly higher CAS than recurrence-free cases. Higher CAS was associated with a greater risk of developing LR (HR, 6.3 and 4.8 for DC and VC, respectively; P < 0.001). CAS remained an independent predictor of relapse-free survival (HR, 7.4 and 4.5 for DC and VC, respectively; P < 0.001) even after accounting for potentially confounding factors [grade, age, comedo necrosis, and radiotherapy (RT)]. Patient stratification using CAS (P < 0.0001) was superior to that by Van Nuys Prognostic Index (VNPI; HR for CAS = 6.2 vs. HR for VNPI = 1.1). Among patients treated with breast-conserving surgery alone, CAS identified patients likely to benefit from adjuvant RT. CAS predicted 10-year LR risk for patients who underwent surgical management alone and identified patients who may be at low risk of recurrence, and for whom adjuvant RT may not be required. CAS demonstrated the highest concordance among the known prognostic models such as VNPI and clinicopathologic variables such as grade, age, and comedo necrosis.

A Prognostic Immunoscore for Relapse-Free Survival Prediction in Colorectal Cancer.

We aimed to establish a novel immunoscore (IS) model based on the transcriptomes of tumor tissues to improve the relapse-free survival (RFS) prediction of colorectal cancer (CRC). CIBERSORT was used to estimate the immune cell fractions based on the Gene Expression Omnibus (GEO) database. Then, a least absolute shrinkage and selection operator regression was applied to construct the IS model based on the immune cell fractions. After screening, four GEO databases were included in the CIBERSORT transformation. A total of 13 types of immune cells were selected and constructed an IS model. In the training set (n = 613) and test set (n = 262), the patients in the high-immunoscore group showed a significant poor RFS than that in the low-immunoscore group. Stratified analysis also found similar results in patients with identical age, sex, adjunctive chemotherapy, or TNM stage I-II. Multivariate Cox regression further demonstrated that the IS model was an independent predictor of RFS in CRC. In addition, the IS was highly associated with the expression of several immune checkpoints, inflammatory mediators, cell cycle, and epithelial-mesenchymal transformation regulators in CRC. We proposed a novel IS model for estimating RFS in CRC patients.

Prognostic role of lymphocyte-to-monocyte ratio in pancreatic neuroendocrine neoplasms.

ObjectivesSystemic inflammation markers have been demonstrated to be associated with prognosis in various tumors. In this study, we aimed to assess the value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index and the counts of lymphocyte, monocyte and neutrophil in predicting prognosis among patients with resected pancreatic neuroendocrine neoplasms (pNENs).MethodsA total of 174 patients were included in the study. Univariate and multivariate analyses were performed to evaluate the predictive roles of inflammation markers for relapse-free survival (RFS) and overall survival (OS) in pNEN patients.ResultsThe optimal cut-off values of NLR, LMR and lymphocyte count were 1.9, 5.0 and 1.4 × 109/L, respectively, determined by the X-tile software. RFS was found to be significantly longer in patients with NLR ≤1.9 (P = 0.041), LMR >5.0 (P < 0.001) and lymphocyte count >1.4 × 109/L (P = 0.002) in comparison to those with NLR >1.9, LMR ≤5.0 and lymphocyte count ≤1.4 × 109/L, respectively. Multivariate analysis revealed that LMR (hazard ratio 0.30, 95% CI 0.11–0.85, P = 0.023) was an independent predictor for RFS, but not NLR or lymphocyte count. For long-term survival analysis, patients with NLR ≤1.9 (P = 0.016) were found to be associated with favorable OS, but NLR was not an independent factor validated by multivariate analysis.ConclusionsPreoperative LMR is an independent systemic inflammation marker to predict relapses in pNEN patients who underwent curative resections, whose clinical value needs to be verified in further large sample-based prospective studies.

Natural history and prognostic factors for localised small bowel adenocarcinoma

ObjectiveSmall bowel adenocarcinoma (SBA) is a rare malignancy with limited evidence regarding outcomes after curative resection of localised disease. We aimed to evaluate presentation and prognostic factors affecting overall survival (OS), relapse-free survival (RFS) and recurrence of SBA.MethodsConsecutive patients with completely resected localised SBA (1979–2019) were retrospectively reviewed for presentation, patient and tumour characteristics, perioperative treatment, recurrence, outcomes, and prognostic factors.ResultsAmong 257 total patients, median age was 58 years. Primary location was in the duodenum, jejunum and ileum in 52%, 29%, and 19% of patients, respectively. Median OS was 57.5 months and median follow-up was 40 months. In multivariate analysis, lymph node involvement, lymphovascular invasion, histologic grade and race were independent predictors of RFS, while race, stage and histologic grade were independent predictors of OS. No significant difference in OS or RFS was seen when evaluating the role of perioperative treatment. Median time to diagnosis from first medical evaluation was 31 days and did not change over time. Overall recurrence rate was 56%. Recurrence rate was higher in ileal (77%), than duodenal (54%) and jejunal (65%) SBA (p=0.01). Recurrence presented most commonly as distant metastasis (71%). Proficient mismatch repair was associated with decreased risk of locoregional recurrence (LR) but increased risk of distant recurrence (DR) when compared with deficient mismatch repair (dMMR) in univariate analysis.ConclusionsDespite advances in diagnostic modalities, this study did not show any improvement in earlier diagnosis of SBA over the course of the past three decades. The predominant pattern of disease recurrence was distant across all SBA locations, but dMMR status demonstrated a robust predilection for LR as opposed to DR. Perioperative treatment did not improve outcomes; however, a lower stage disease was seen in patients that received neoadjuvant therapy, suggesting further exploration of this approach.

The interplay of adiposity, metabolic factors, and tumor infiltrating lymphocytes in an East Asian breast cancer cohort.

e14207 Background: Breast cancer is rapidly emerging in East Asian countries in recent 2 decades. Unlike western countries in which obesity are quite prevalent and contributes to BC patients, the body mass index (BMI) of BC patients in East Asian countries are usually normal to no more than overweight. In our previous study, we noticed a 30% incidence of crown-like structure of breast (CLS-B) in our BC patients. Despite a lower BMI in this East Asian cohort than the US cohort, the body fat percentage (BF%) is significantly higher in the East Asian The roles of tumor infiltrating lymphocytes (TILs) in BC are inconslusive in different disease contexts. This study aims to decipher the interplay of adiposity, metabolic factors, and TILs in a BC cohort from an East Asian country. Methods: Breast cancer patients from National Taiwan University Hospital were prospectively enrolled into the protocol. Clinicopathologic factors were collected from electronic medical records. Fasting serum collected prior to surgery was used to quantify metabolic factors, including lipid and glucose profiles. Adiposity, including BF% and BMI were quantified by bioimpedance analysis method prior to surgery. Immunohistochemical staining from formalin-fixed, paraffin-embedded BC tumor samples were done to profile TILs by pathologist. CLS-B was stained and interpreted by pathologists. The correlation of TILs with different clinicopathologic factors, adiposity, or relapse-free survival (RFS) were analyzed. Results: 72 BC patients were included in this analysis. The density of CLS-B positively correlates with tumor infiltrating lymphocyte (TIL) percentage ( p = .042), higher BF% correlates with higher regulatory T cells ( p = .026) and tumor associated macrophages (TAM, p = .010), high glucose level is associated with higher CD56 ( p = .040) and higher TAMs ( p &lt; 0.0001). Higher BMI is also associated with higher TAMs ( p= .005). In multivariate analysis, TAMx M2 macrophage is an independent predictor for RFS. Higher TAM level is associated with shorter RFS. Conclusions: Higher TAMs are associated with metabolic alterations such as higher adiposity, higher glucose level, and higher BMI. This result suggests a potential interplay between higher TAMs, altered metabolic factors, and worse RFS.

Oncological control in high-risk prostate cancer after radical prostatectomy and salvage radiotherapy compared to radiotherapy plus primary hormone therapy

IntroductionIn patients with high-risk localized prostate cancer (HRPCa), multimodal treatment plays a fundamental role. ObjectiveTo compare relapse-free survival (RFS) in patients with HRPCa, treated primarily with radiotherapy (RT)+hormone therapy (HT) versus radical prostatectomy (RP) and salvage RT (sRT)±HT when biochemical recurrence (BCR) appears. Material and methodsRetrospective analysis of 226 patients with HRPCa (1996–2008), treated primarily with RT+HT (n=137) or RP (n=89). The Kaplan–Meier method has been used to evaluate survival and the log-rank test has been used to evaluate the contrast between the different categories of the variables. Multivariate analysis has been performed using Cox regression to determine variables with an impact on RFS with statistical significance (p<0.05). ResultsThe median follow-up of the series was 111 (IQR 85–137.5) months. After RT+HT, 32 (23.4%) patients relapsed, and after RP 41 (46.1%) cases, (p=0.0001). When comparing the primary treatments, the RFS at 5 and 10 years was higher after RT+HT versus RP in monotherapy (p=0.001). The primary treatment with RT+HT reduced the risk of BCR when compared to the RP (HR=0.41, p=0.002). The estimation of the RFS at 5 and 10 years after RP+sRT±HT was 89.7 and 87.1%, while after primary RT+HT was 91.6 and 71.1%, respectively (p=0.01). The only factor that behaved as an independent predictor of RFS was the multimodal treatment with RP+sRT±HT when BCR showed up (HR=2.39, p=0.01). ConclusionIn HRPCa, multimodal treatment with RP+sRT±HT if BCR, significantly improves RFS with respect to treatment with RT+HT.

Control oncológico en cáncer de próstata de alto riesgo tras prostatectomía radical y radioterapia de rescate en comparación con radioterapia más hormonoterapia primaria

IntroductionIn patients with high-risk localized prostate cancer (HRPCa), multimodal treatment plays a fundamental role. ObjectiveTo compare relapse-free survival (RFS) in patients with HRPCa, treated primarily with radiotherapy (RT)+hormone therapy (HT) versus radical prostatectomy (RP) and salvage RT (sRT)±HT when biochemical recurrence (BCR) appears. Material and methodsRetrospective analysis of 226 patients with HRPCa (1996-2008), treated primarily with RT+HT (n=137) or RP (n=89). The Kaplan-Meier method has been used to evaluate survival and the log-rank test has been used to evaluate the contrast between the different categories of the variables. Multivariate analysis has been performed using Cox regression to determine variables with an impact on RFS with statistical significance (P<0.05). ResultsThe median follow-up of the series was 111 (IQR 85-137.5) months. After RT+HT, 32 (23.4%) patients relapsed, and after RP (P=0.0001), 41 (46.1%) cases. When comparing the primary treatments, the RFS at 5 and 10 years was higher after RT+HT versus RP in monotherapy (P=0.001). The primary treatment with RT+HT reduced the risk of BCR when compared to the RP (HR=0.41, P=0.002). The estimation of the RFS at 5 and 10 years after RP+sRT±HT was 89.7 and 87.1%, while after primary RT+HT was 91.6 and 71.1%, respectively (P=0.01). The only factor that behaved as an independent predictor of RFS was the multimodal treatment with RP+sRT±HT when BCR showed up (HR=2.39, P=0.01). ConclusionIn HRPCa, multimodal treatment with RP+sRT±HT if BCR, significantly improves RFS with respect to treatment with RT+HT.

High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma

Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previously we reported that definitive endoderm from which liver was derived, expressed Globo H, SSEA-3 and SSEA-4. In this study, we examined the expression of their biosynthetic enzymes, FUT1, FUT2, B3GALT5 and ST3GAL2, in 135 hepatocellular carcinoma (HCC) tissues by qRT-PCR. High expression of either FUT1 or B3GALT5 was significantly associated with advanced stages and poor outcome. Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with high expression of either FUT1 or B3GALT5 (P = 0.024 and 0.001, respectively) and shorter overall survival (OS) for those with high expression of B3GALT5 (P = 0.017). Combination of FUT1 and B3GALT5 revealed that high expression of both genes had poorer RFS and OS than the others (P < 0.001). Moreover, multivariable Cox regression analysis identified the combination of B3GALT5 and FUT1 as an independent predictor for RFS (HR: 2.370, 95% CI: 1.505–3.731, P < 0.001) and OS (HR: 2.153, 95% CI: 1.188–3.902, P = 0.012) in HCC. In addition, the presence of Globo H, SSEA-3 and SSEA-4 in some HCC tissues and their absence in normal liver was established by immunohistochemistry staining and mass spectrometric analysis.

Tumour front inflammation and necrosis are independent prognostic predictors in high-grade urothelial carcinoma of the bladder

AimsInflammation and necrosis have been associated with prognosis in multiple epithelial malignancies. Our objective was to evaluate inflammation and necrosis in a cohort of patients with high-grade urothelial carcinomas of...