Reduced Recurrence-free Survival Research Articles

Fibrinogen to pre-albumin ratio is an independent prognostic index for patients with pancreatic ductal adenocarcinoma after radical resection

BackgroundThis study aims to elucidate the significance of the preoperative fibrinogen to pre-albumin ratio (FPR) in predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC), a correlation not extensively explored previously.MethodsA cohort of 563 patients diagnosed with PDAC and subjected to radical surgical resection was examined. We meticulously documented a range of inflammatory markers, clinical-pathological features, and oncological outcomes. The prognostic value of preoperative FPR was assessed using Kaplan–Meier survival analysis and Cox proportional hazards regression modeling. Furthermore, the predictive accuracy of FPR was evaluated through time-dependent receiver operating characteristic (ROC) curves and decision curve analyses (DCA).ResultsThe determined optimal threshold for FPR was 14.77, which facilitated the stratification of patients into groups with low and high FPR levels. Notably, patients in the high FPR cohort exhibited significantly reduced recurrence-free survival (RFS) and overall survival (OS) rates compared to their low FPR counterparts. Multivariate Cox regression analysis underscored FPR as an independent prognostic indicator for both RFS and OS. In comparison to the neutrophil-to-lymphocyte ratio (NLR), FPR demonstrated superior prognostic accuracy and clinical utility.ConclusionThe preoperative fibrinogen to pre-albumin ratio serves as an independent prognostic marker for RFS and OS among PDAC patients undergoing radical resection. Our findings suggest that FPR could be a valuable addition to the current prognostic models, potentially guiding therapeutic decision-making and patient management strategies in PDAC.

Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer.

Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC). Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4. ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001). ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.

The relationship between cancer associated fibroblasts biomarkers and prognosis of breast cancer: a systematic review and meta-analysis.

To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment. PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias. Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor-β (PDGFR-β) (P=0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) (P<0.0001), matrix metalloproteinase (MMP) 9 (P<0.0001), MMP 11 (P<0.0001) and MMP 13 (P=0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of α-smooth muscle actin (α-SMA) (P=0.0002), podoplanin (PDPN) (P=0.0008), and PDGFR-β (P=0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR-β expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2). The high expression of α-SMA, PDPN, PDGFR-β in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.

Diagnostic and prognostic potential of the intra-tumoral microbiota profile in HPV-independent endocervical adenocarcinoma.

Microbial community dynamics have been involved in numerous diseases, including cancer. The diversity of intertumoral microbiota in human papillomavirus independent endocervical adenocarcinoma (HPVI ECA) is not well-characterized. Our objective is to delineate the intratumoral microbiota profile in HPVI ECA and investigate its potential influence on oncogenesis. We analyzed 45 HPVI ECA cases, comprising 36 gastric-type ECA (GEA) and 9 clear cell carcinomas (CCC). We compared the microbial composition within cancerous and adjacent noncancerous tissue samples using 5R-16S ribosomal DNA sequencing. Further, we investigated the correlation between specific microbes and clinical-pathological metrics as well as patient outcomes. Our findings demonstrate notable differences in the microbial spectra between cancerous and adjacent noncancerous tissues. Amongst HPVI ECA subtypes, GEAs exhibit more microbial variations compared to CCCs. Using the Random Forest algorithm, we identified two distinct microbial signatures that could act as predictive biomarkers for HPVI ECA and differentiate between GEA and CCC. Varied microbial abundances was related to clinical characteristics of HPVI ECA patients. In addition, high levels of Micrococcus and low levels of unknown genus75 from the Comamonadaceae family were associated with poorer outcomes in HPVI ECA patients. Similarly, an abundance of Microbacterium correlated with reduced overall survival (OS), and a high presence of Streptococcaceae family microbes was linked to reduced recurrence-free survival (RFS) in GEA patients. Intriguingly, a high abundance of Micrococcus was also associated with a worse OS in GEA patients. The study reveals distinct microbial signatures in HPVI ECA, which have potential as biomarkers for disease prognosis. The correlation between these tumor-associated microbiota features and clinicopathological characteristics underscores the possibility of microbiome-based interventions. Our research provides a foundation for more in-depth studies into the cervical microbiome's role in HPVI ECA.

The effects of dexmedetomidine on postoperative tumor recurrence and patient survival after breast cancer surgery: a feasibility study

PurposeDexmedetomidine (Dexmed) is a highly selective alpha 2 adrenoceptor (α2-AR) agonist with excellent sedation and analgesic effects and is frequently used in breast cancer surgery. However, the exact impact of Dexmed on breast cancer prognosis is still unclear. The primary objective of this pilot study was to explore study feasibility (recruitment and dropout rates) for future large-scale randomized controlled trial (RCT) to test the hypothesis that intraoperative Dexmed reduced recurrence-free survival (RFS) and overall survival (OS) in patients after breast cancer surgery.MethodsInterviews with patients were performed during the anesthetic preoperative visit for informed consent. Adult females scheduled for a mastectomy due to primary breast cancer were 1:1 randomised to saline (Group Control) or Dexmed (Group Dexmed) treatment groups. The primary outcomes were descriptions of study feasibility (recruitment and dropout rates). We also performed a preliminary analysis of RFS (time from surgery to the earliest date of recurrence/metastasis) and OS (time from surgery to the date of all-cause death) and collected data on percentages/numbers of circulating immune cells at pre- and 24 h post-operation.ResultsA total of 964 patients were screened; 40% (385/964) met the inclusion criteria, among which 39% (150/385) were enrolled and randomly assigned to either Group Control (n = 75) or Group Dexmed (n = 75). The median follow-up duration was 49 months (interquartile range (IQR): 34–58 months) for Group Control and 48 months (IQR: 33–60 months) for Group Dexmed. Five percent (5%, 8/150) patients were lost to follow-up and 1% (2/150) died. There was no significant difference in RFS and OS. The percentage/number of natural killer (NK), B and T-cell subsets and the CD4+/CD8+ ratio were similar between groups at 24 h post-operation.ConclusionThe pilot study was feasible to deliver. In a future definitive trial, the lower recruitment rate may be improved by increasing the number of anesthesiologists involved in the study. The study about the effects of Dexmed on long-term prognoses of breast cancer patients that is planned to follow this pilot study is a large-scaled randomized control study with the aim of providing evidence-based guidelines for rational use of Dexmed in patients undergoing breast cancer surgery.Trial registrationRegistered at ClinicalTrials.gov on October 20, 2016 (ID: NCT03109990).Graphical

Immune landscape of vulvar cancer patients treated with surgery and adjuvant radiotherapy revealed restricted T cell functionality and increased IL-17 expression associated with cancer relapse.

For vulvar cancers, radiotherapy is targeting cancer cells, but also affects the host immune system. As this may affect treatment outcome, in this prospective study, we characterized the individual T cell immune milieu induced by surgery and adjuvant radio +/- chemotherapy (aRT) systemically in the blood of vulvar cancer patients and found increased frequencies of Interleukin (IL)-17-producing CD4+ and CD8+ T cells after aRT while frequencies of Th1 and perforin-producing CD8+ killer cells were strongly diminished. Phenotypic characterization revealed enhanced expression of the ectonucleotidase CD39 on Th17 and Tc17 cells as well as CD8+ perforin+ cells after aRT. Furthermore, the aRT cohort exhibited increased proportions of Programmed Cell Death Protein (PD-1) expressing cells among Th1 and CD8+ perforin+ cells, but not among Th17 and Tc17 cells. High post-therapeutic levels of Th17 and Tc17 cells and low proportions of Th1 and CD8+ perforin+ cells expressing PD-1 was associated with reduced recurrence free survival on follow-up. In conclusion, our study defines individual therapy-induced changes in the cellular immune milieu of patients and their association with cancer relapse. Our results may help to explain differences in the individual courses of disease of vulvar cancer patients and suggest PD-1 and IL-17 as targets for immunotherapy in vulvar cancer.

Neutrophil extracellular trap as a predictive marker to cisplatin-based chemotherapy for patients with muscle-invasive bladder cancer.

e16600 Background: Cisplatin-based chemotherapy is the recommended therapy for muscle-invasive bladder cancer (MIBC), in both the neoadjuvant and first-line settings. However, the efficacy of MIBC for chemotherapy is only about 40%~60%. Patients without clear benefits from cisplatin-based chemotherapy still suffer from the potential toxicity, possibly missing the timing for other effective treatments. Therefore, predictors of therapy response are urgently needed. Neutrophils form neutrophil extracellular traps (NETs), a network structure, and growing evidence indicated that it could be a prognostic and predictive marker in cancer. In bladder cancer, NETs were involved in radio-resistance, but the predictive role of chemotherapy is unclear. This study constructed a NET-related signature that predicted chemotherapy efficacy for MIBC patients. Methods: Transcriptome datasets were obtained from the transurethral resection of bladder tumor (TURBT) and metastatic lesion specimens. A dataset (GSE169455) of 149 MIBC patients who received preoperative cisplatin-based chemotherapy (neoadjuvant or induction) was enrolled for the training cohort. We used the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model to select candidate molecules based on the 250 NETs-initial biomarkers collected from the literature, and further developed a NETs-associated signature score (NETs-score) for therapeutic response prediction. The dataset reported by Taber A et al. of 96 MIBC patients who received cisplatin-based chemotherapy (neoadjuvant or first-line) was used as a validation cohort. Immunohistochemistry (IHC) was conducted to evaluate the potential role of NET-related genes in 51 patients who received neoadjuvant chemotherapy at our center from 2012 to 2019. Results: We constructed the NETs-score with 11 NETs-related genes by the LASSO Cox model. A higher NET score was observed in non-responders compared to responders in the training cohort (P&lt;0.001). These results were confirmed in the validation cohort (P=0.006). Moreover, high NETs-score indicated reduced recurrence-free survival (RFS) [HR=2.07, 95% CI (1.26-3.40), P=0.003], cancer-specific survival (CSS) [HR=1.87, 95% CI (1.12-3.12), P=0.014], and overall survival (OS) [HR=1.83, 95% CI (1.13-2.94), P=0.012] among MIBC patients. Furthermore, in the IHC cohort, citrullinated histone H3 (H3Cit) as a hallmark of NETs, was an independent predictor of chemotherapy resistance as determined by the multivariate logistic regression analysis [OR=5.94, 95% CI 1.20–45.50, P=0.045]. Conclusions: In conclusion, our study suggested that NET was a predictive and prognostic biomarker for MIBC patients with cisplatin-based chemotherapy. [Table: see text]

MACC1 as a Potential Target for the Treatment and Prevention of Breast Cancer

Metastasis associated in colon cancer 1 (MACC1) is an oncogene first identified in colon cancer. MACC1 has been identified in more than 20 different types of solid cancers. It is a key prognostic biomarker in clinical practice and is involved in recurrence, metastasis, and survival in many types of human cancers. MACC1 is significantly associated with the primary tumor, lymph node metastasis, distant metastasis classification, and clinical staging in patients with breast cancer (BC), and MACC1 overexpression is associated with reduced recurrence-free survival (RFS) and worse overall survival (OS) in patients. In addition, MACC1 is involved in BC progression in multiple ways. MACC1 promotes the immune escape of BC cells by affecting the infiltration of immune cells in the tumor microenvironment. Since the FGD5AS1/miR-497/MACC1 axis inhibits the apoptotic pathway in radiation-resistant BC tissues and cell lines, the MACC1 gene may play an important role in BC resistance to radiation. Since MACC1 is involved in numerous biological processes inside and outside BC cells, it is a key player in the tumor microenvironment. Focusing on MACC1, this article briefly discusses its biological effects, emphasizes its molecular mechanisms and pathways of action, and describes its use in the treatment and prevention of breast cancer.

Expression and the Prognostic Value of Biglycan in Gastric Cancer.

Background Biglycan (BGN) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer. Material and Methods. Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets (n = 64 and n = 432) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. Protein-protein interaction (PPI) analysis was performed on gastric cancer-related genes and BGN targets, and those interactions with confidence interval (CI) ≥ 0.7 were chosen to construct a PPI network. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Gene Transcription Regulation Database (GTRD) and ALGGEN-PROMO predicted the transcription factor binding sites (TFBSs) of the BGN promoter. BGN protein level in gastric cancer tissue was determined by immunohistochemistry (IHC). Bioinformatic analysis predicted the putative TFs of BGN. Results For gastric cancer, the mRNA expression level of BGN in tumor tissue was significantly higher than that in normal tissue. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN was significantly enriched in gene signatures related to metastasis and poor prognosis, revealing that BGN might be associated with cell proliferation, poor differentiation, and high invasiveness of gastric cancer. Meanwhile, the putative TFs, including AR, E2F1, and TCF4, were predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion High expression of BGN mRNA was significantly related to poor prognosis, which suggested that BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.

Abstract 5115: Combine high risk factors with circulating tumor DNA (ctDNA) to assist adjuvant chemotherapy (ACT) decision in Stage II colorectal cancer (CRC)

Abstract Background: Approximately 10% to 15% have residual disease after surgery in patients with stage II CRC. Identification of this high-risk population and treatment with ACT could potentially reduce their risk of recurrence. However, the relative contribution of the factors used to define high risk stage II disease needs better understanding, although post-surgical ctDNA has been studied as a marker for an elevated risk of recurrence in stage I-III colorectal cancer. Methods: Individual data from 3 early colorectal cancer clinical studies(Tie, 2016;Reinert, 2019; Chen, 2021) that included information on high-risk factors and post-surgical ctDNA status were collected and reanalysed for 595 patients with or without ACT. Results: In stage II CRC patients with ctDNA-negative not treated with ACT form the Tie cohort, with high-risk status (n=42) showed a significantly reduced recurrence-free survival (RFS) compared to those with low-risk status(n=122) [HR, 3.283; 95%CI, 1.398 to 14.18; P = 0.0116], but in the ctDNA-negative patients with high-risk status, ACT (n=32) or not did not affect the RFS(P=0.1758). It meant false negatives of ctDNA made for bias of survival analysis results. Interestingly, in other two cohorts of stage II CRC patients with ctDNA-negative not treated with ACT, high-risk status showed no difference in RFS compared to low-risk status (p=0.3429 and 0.3173, respectively). In addition to the low sample size, the contribution of defined high-risk factors in prognosis was worth exploring which meant pseudo high-risk status also affect survival analysis results. And there were big differences in the high-risk factors included in the three cohorts especially in ctDNA-negative patients, such as the proportion of lymph nodes (LN) yield &amp;lt;12 seemed higher in Tie cohort. Conclutions: It was not enough to predict recurrence depend on ctDNA status alone for stage II CRC. Different risk factors might have different prognostic weights so that different combinations of post-surgical ctDNA status and risk factors might be used to make more accurate ACT decision. Citation Format: Xie Gui Yuan, Liu Miao, Huang Meng Li. Combine high risk factors with circulating tumor DNA (ctDNA) to assist adjuvant chemotherapy (ACT) decision in Stage II colorectal cancer (CRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5115.

SATB2 expression in human tumors: A tissue microarray study on more than 15,000 tumors

Abstract Introduction/Objective Introduction: Special AT-rich sequence-binding protein 2 (SATB2) binds to DNA in specific nuclear matrix attachment regions and facilitates chromatin remodeling. SATB2 immunostaining is commonly used as a marker for colorectal adenocarcinoma and osteosarcoma. Methods/Case Report Methods: To comprehensively evaluate SATB2 expression in normal and tumor tissues, a tissue microarray containing 15,012 samples from 120 different tumor types and subtypes and 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. Results (if a Case Study enter NA) Result: SATB2 positivity was found in 89 different tumor types including 59 with at least one moderately positive and 38 tumor types with at least one strongly positive tumor. Most frequent and strongest expression were found in adenomas (94-96%), adenocarcinomas (86%) and various subtypes of neuroendocrine neoplasms (43-100%) of the colorectum and appendix, Merkel cell carcinoma (74%), osteosarcomas (60%), and papillary renal cell carcinoma (RCC) (52%). In colorectal cancer, weak SATB2 expression was linked to high pT (p&amp;lt;0.0001), nodal metastasis (p&amp;lt;0.0001), right-sided tumor location (p&amp;lt;0.0001), microsatellite instability (p=0.0004), and BRAF mutations (p&amp;lt;0.0224). In papillary RCC, low SATB2 was associated with high pT (p=0.0197), distant metastasis (p=0.042), and reduced tumor specific survival (p=0.0395). In clear cell RCC, low SATB2 was linked to high pT (p&amp;lt;0.0001), high UICC stage (p&amp;lt;0.0001), high Thoenes grade (p=0.0178), and reduced recurrence free survival (p=0.0216). Conclusion SATB2 expression can occur in many different tumor entities. Strong SATB2 expression argues for a colorectal tumor origin within adenocarcinomas and neuroendocrine neoplasms. Weak SATB2 expression reflects cancer progression and poor prognosis in colorectal and kidney cancer.

PD53-03 LONG TERM OUTCOMES OF DYNAMIC SENTINEL LYMPH NODE BIOPSY (DSNB) FOR CLINICALLY IMPALPABLE (CN0) PENILE CANCER PATIENTS-AN EUROGEN STUDY

You have accessJournal of UrologyPenile & Testicular Cancer: Penile & Testicular Cancer II (PD53)1 Sep 2021PD53-03 LONG TERM OUTCOMES OF DYNAMIC SENTINEL LYMPH NODE BIOPSY (DSNB) FOR CLINICALLY IMPALPABLE (CN0) PENILE CANCER PATIENTS-AN EUROGEN STUDY Edoardo Pozzi, Omer Onur Cakir, Fabio Castiglione, Nicolo' Schifano, Paul Hadway, Raj Nigam, Rowland Rees, Maarten Albersen, Arie Parnham, Maurice Lau, Hussain M. Alnajjar, Vijay Sangar, and Asif Muneer Edoardo PozziEdoardo Pozzi More articles by this author , Omer Onur CakirOmer Onur Cakir More articles by this author , Fabio CastiglioneFabio Castiglione More articles by this author , Nicolo' SchifanoNicolo' Schifano More articles by this author , Paul HadwayPaul Hadway More articles by this author , Raj NigamRaj Nigam More articles by this author , Rowland ReesRowland Rees More articles by this author , Maarten AlbersenMaarten Albersen More articles by this author , Arie ParnhamArie Parnham More articles by this author , Maurice LauMaurice Lau More articles by this author , Hussain M. AlnajjarHussain M. Alnajjar More articles by this author , Vijay SangarVijay Sangar More articles by this author , and Asif MuneerAsif Muneer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002080.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Dynamic sentinel lymph node biopsy (DSNB) is routinely offered to patients presenting with penile cancer ³T1G2 and clinically impalpable inguinal lymph nodes (cN0). We aimed to assess the diagnostic accuracy of DSNB, cancer specific survival (CSS) in patients with positive DSNB and positive LN at further radical lymph node groin dissection (RLND). METHODS: An eUROGEN retrospective study of 509 penile cancer patients undergoing DSNB. Age, type of primary surgery, complications after DSNB, tumour stage, tumour grade were all reported. Number of true positives, true negatives, false negatives and false positives were recorded. False negative was defined as inguinal lymph node recurrence within 12 months from a previous negative DSNB. Sensitivity and specificity of DSNB were calculated. Kaplan-Meier analysis was used to estimate the 5-years CSS and recurrence free-survival rates among patients with positive DNSB and RLND. RESULTS: Overall, 509 patients with cN0 penile cancer were identified. The median follow-up for local recurrence and CSS were 62.5 months (IQR 28.5-91) and 63.5 months (IQR 26.5-90) respectively. All patients underwent DSNB at the time of primary surgery or as a delayed procedure. A total of 993 groins were studied. 37 patients had positive histology at DSNB. 37 patients underwent further RLND with 34 of them having positive histology at RLND. At DSNB true positives were 37 (7.27%), false negatives 3 (0.59). Sensitivity and specificity were 92.5% and 100% respectively. Multivariable Cox regression analysis identified positive LN histology both at DSNB and at RLND as predictors for reduced CSS (HR 4.59, CI: 2.35-8.95, p<0.0001) and (HR 5.64, p = 0.0004). Likewise, positive LN histology at DSNB and RLND was a predictor for reduced recurrence free survival HR 4.04 and HR 6.98 all p<0.0001. At Kaplan-Meier analysis, the 5-years CSS for positive LN histology at DSNB/RLND were 69.7% and 69.6% respectively. CONCLUSIONS: DSNB is now an established procedure with a sensitivity of 92.5%. Positive histology after DSNB and subsequent RLND is a strong predictor of reduced CSS and recurrence free survival. Source of Funding: n/a © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e917-e917 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Edoardo Pozzi More articles by this author Omer Onur Cakir More articles by this author Fabio Castiglione More articles by this author Nicolo' Schifano More articles by this author Paul Hadway More articles by this author Raj Nigam More articles by this author Rowland Rees More articles by this author Maarten Albersen More articles by this author Arie Parnham More articles by this author Maurice Lau More articles by this author Hussain M. Alnajjar More articles by this author Vijay Sangar More articles by this author Asif Muneer More articles by this author Expand All Advertisement Loading ...

The Prognostic Value of FGFR3 Expression in Patients with T1 Non-Muscle Invasive Bladder Cancer.

PurposeFibroblast growth factor receptor 3 (FGFR3) alterations are frequent in non-muscle-invasive bladder cancer (NMIBC), although current data regarding the prognostic and therapeutic relevance are inconsistent. We analyzed the prognostic role of FGFR3 mRNA expression in stage T1 NMIBC.Patients and MethodsThe mRNA expression of FGFR3 and cyclin-dependent kinase inhibitor 2A (CDKN2A) was measured by RT-qPCR in 80 patients with stage T1 NMIBC treated with transurethral resection of the bladder and correlated with clinical data and KRT5 and KRT20 expression, used as surrogate markers for basal and luminal subtypes, respectively.ResultsFGFR3 and CDKN2A transcript levels were not correlated. FGFR3 expression was associated with the expression of KRT5 (p=0.002) and KRT20 (p < 0.001). CDKN2A expression was negatively correlated with KRT5 (p=0.030). In Kaplan–Meier analysis and univariable Cox regression analysis, high FGFR3 expression was associated with significantly reduced recurrence-free survival (RFS) (HR=3.78; p < 0.001) and improved overall survival (OS) (HR=0.50; p=0.043), while high CDKN2A expression was associated with reduced OS (HR=2.34; p=0.034). Patient age was the only clinicopathological parameter associated with reduced OS (HR=2.29; p=0.022). No parameter was an independent prognostic factor in multivariable analysis. Next, we stratified the patients depending on their lineage differentiation. In univariable analysis, the prognostic effect of FGFR3 and CDKN2A was observed primarily in patients demonstrating high expression of KRT5 or KRT20, whereas high FGFR3 expression was associated with significantly reduced RFS, irrespective of instillation therapy.ConclusionStage T1 NMIBC patients with high FGFR3 expression show shorter RFS but better OS than patients with low FGFR3 expression.

Albumin-to-alkaline phosphatase ratio as a predictor of tumor recurrence and prognosis in patients with early-stage hepatocellular carcinoma undergoing radiofrequency ablation as initial therapy

Objective Albumin-to-alkaline phosphatase ratio (AAPR), a newly developed blood biomarker, has been reported to have prognostic value in several types of cancer. This study aimed to investigate the predictive value of AAPR in patients with early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) as initial therapy. Methods This retrospective study analyzed 445 patients with newly diagnosed HCC undergoing RFA as initial therapy. A series of survival analyses were performed to evaluate the prognostic value of AAPR. Univariate and multivariate analyses were performed to identify independent prognostic factors. An AAPR-based nomogram was constructed, and its predictive performance was validated. Results Patients with a low AAPR had a significantly reduced recurrence-free survival (RFS) and overall survival (OS) compared with those with a high AAPR. AAPR was found to be an independent prognostic indicator and showed superior discrimination efficacy than other liver function indices. The AAPR-based nomogram had a concordance index value of 0.72 (95% confidence interval [CI]: 0.65–0.79) in the training cohort and 0.72 (95% CI: 0.63–0.81) in the validation cohort, which significantly outperformed other existing staging systems. Conclusions AAPR serves as a promising indicator of prognosis in patients with early-stage HCC undergoing RFA. The AAPR-based nomogram might contribute to individualized prognosis prediction and clinical decision making.

A step towards personalizing next line therapy for resected pancreatic and related cancer patients: A single institution's experience

BackgroundThere is a lack of precision medicine in pancreatic ductal adenocarcinoma (PDA) and related cancers, and outcomes for patients with this diagnosis remain poor despite decades of research investigating this disease. Therefore, it is necessary to explore novel therapeutic options for these patients who may benefit from personalized therapies. ObjectiveMolecular profiling of hepatopancreaticobiliary malignancies at our institution, including but not limited to PDA, was initiated to assess the feasibility of incorporating molecular profiling results into patient oncological therapy planning. MethodsAll eligible patients from Thomas Jefferson University (TJU) with hepatopancreaticobiliary tumors including PDA, who agreed to molecular testing profiling, were prospectively enrolled in a registry study from December 2014 to September 2017 and their tumor samples were tested to identify molecular markers that can be used to guide therapy options in the future. Next generation sequencing (NGS) and protein expression in tumor samples were tested at CLIA-certified laboratories. Prospective clinicopathologic data were extracted from medical records and compiled in a de-identified fashion. ResultsSeventy eight (78) patients were enrolled in the study, which included 65/78 patients with PDA (local and metastatic) and out of that subset, 52/65 patients had surgically resected PDA. Therapy recommendations were generated based on molecular and clinicopathologic data for all enrolled patients. NGS uncovered actionable alterations in 25/52 surgically resected PDAs (48%) which could be used to guide therapy options in the future. High expression of three proteins, TS (p = 0.005), ERCC1 (p = 0.001), and PD-1 (p = 0.04), was associated with reduced recurrence-free survival (RFS), while TP53 mutations were correlated with longer RFS (p = 0.01). ConclusionsThe goal of this study was to implement a stepwise strategy to identify and profile resected PDAs at our institution. Consistent with previous studies, approximately half of patients with resected PDA harbor actionable mutations with possible targeted therapeutic implications. Ongoing studies will determine the clinical value of identifying these mutations in patients with resected PDA.

High CXCR4 expression in adenoid cystic carcinoma of the head and neck is associated with increased risk of locoregional recurrence

AimTreatment options for head and neck adenoid cystic carcinoma (AdCC) are limited in advanced disease. Chemokine receptor type 4 (CXCR4) is present in various tumour types, including AdCC. Upregulation is...

&lt;p&gt;Poor Prognosis With Coexistence Of &lt;em&gt;EGFR&lt;/em&gt; T790M Mutation And Common &lt;em&gt;EGFR&lt;/em&gt;-Activating Mutation In Non- Small Cell Lung Cancer&lt;/p&gt;

PurposePrevious studies have shown that the presence of EGFR T790M mutation may reduce the treatment efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer. However, little is known about the clinical features and outcomes of EGFR T790M mutation in pretreated patients with NSCLC.Patients and methodsThe clinical features of EGFR-activating and T790M mutations were assessed in a large cohort of patients with EGFR-TKI-naïve NSCLC (all/EGFR mutations, n=16,347/7,687). The correlation between the pretreatment T790M mutation status and clinical outcomes was evaluated using univariate and multivariate analyses.ResultsPretreatment T790M mutation was reported in 1.39% of the patients and coexisted with an EGFR-activating or uncommon mutation. The dual EGFR T790M and common EGFR-activating mutations were more likely to be detected in lung adenocarcinoma, whereas single T790M mutation was more prevalent in non-adenocarcinomas. The presence of de novo T790M mutation correlated with reduced recurrence-free survival (RFS) in patients with NSCLC (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.67–6.79, P = 0.001). After molecular stratification, T790M mutation was shown to exert adverse effects on the RFS of EGFR 19-del group (OR 2.89, 95% CI 1.10–7.91, P = 0.028) and EGFR L858R group (OR 3.43, 95% CI 1.33–8.88, P = 0.013). Furthermore, pretreatment T790M mutation promoted tumor metastasis to different sites.ConclusionT790M-positive tumors presented special clinical features, and the coexistence of T790M and common EGFR-activating mutations was associated with poor prognosis in patients with NSCLC.

The impact of failure to achieve symptom control after resection of functional neuroendocrine tumors: An 8-institution study from the US Neuroendocrine Tumor Study Group.

The goals of resection of functional neuroendocrine tumors (NETs) are two-fold: Oncological benefit and symptom control. The interaction between the two is not well understood. All patients with functional NETs of the pancreas, duodenum, and ampulla who underwent curative-intent resection between 2000 and 2016 were identified. Using Cox regression analysis, factors associated with reduced recurrence-free survival (RFS) were identified. Two-hundred and thirty patients underwent curative-intent resection. Fifty-three percent were insulinomas, 35% gastrinomas, and 12% were other types. Twenty-one percent had a known genetic syndrome, 23% had lymph node (LN) positivity, 80% underwent an R0 resection, and 14% had no postoperative symptom improvement (SI). Factors associated with reduced RFS included noninsulinoma histology, the presence of a known genetic syndrome, LN positivity, R1 margin, and lack of SI. On multivariable analysis, only the failure to achieve SI following resection was associated with reduced RFS. Considering only those patients with an R0 resection, failure to achieve SI was associated with worse 3-year RFS compared with patients having SI (36% vs 80%; P = 0.006). Failure to achieve symptomatic improvement after resection of functional NETs is associated with worse RFS. These patients may benefit from short-interval surveillance imaging postoperatively to assess for earlier radiographical disease recurrence.

The impact of failure to achieve symptom control after resection of functional neuroendocrine tumors: An 8-institution study from the US Neuroendocrine Tumor Study Group

Introduction: The goals of resection for pts with functional neuroendocrine tumors(F-NETs) are two-fold: oncologic benefit and symptom control. The interaction between the two is not well-understood. Method: All pts with F-NETs of the pancreas, liver, duodenum, and ampulla who underwent curative-intent resection from 2000-2016 were identified. Cox regression analysis was utilized to determine factors associated with reduced recurrence-free survival(RFS). A multivariable model was created by incorporating variables associated with RFS with p< 0.1. Results: Of 260 pts with resected F-NETs, 230 underwent curative-intent resection. 53% were insulinomas, 35% gastrinomas, and 12% other. 21% had a known genetic syndrome(majority MEN-1), 23% had LN(+) disease, 80% underwent an R0 resection, and 14% had no postoperative symptom improvement(SI). Pts who did have SI were more likely to have an insulinoma(p=0.01), no genetic syndrome(p=0.001), and R0 resection(p=0.007). LN(+) disease did not correlate with postoperative SI. Factors associated with reduced RFS included non-insulinoma histology, known genetic syndrome, LN(+) disease, R1 margin, and lack of SI. On MV analysis, only the failure to achieve SI following resection persisted as being associated with reduced RFS(Table). Considering only pts with an R0 resection, failure to achieve SI was still associated with worse 3-yr RFS compared to pts with SI(36%vs80%;p=0.006). Conclusions: Failure to achieve symptomatic improvement after resection of functional NETs is associated with worse recurrence-free survival, even when accounting for histologic type, presence of genetic syndromes, R1 resection, and LN involvement. These patients may benefit from short-interval periodic imaging postoperatively to assess for earlier radiographic recurrence of disease.Tabled 1FP04-05 Table 1VariableUnivariableMultivariableHazard Ratio95% CIp-valueHazard Ratio95% CIp-valueType of Functional TumorInsulinomaRef----Ref----Gastrinoma2.8(1.3-6.1)0.0061.1(0.6-2.0)0.75Other (glucagonoma, somatostatinoma, VIPoma)2.7(1.0-7.2)0.042------Known Genetic Syndrome1.8(0.9-3.5)0.0770.68(0.2-2.0)0.49Lymph Node Positive1.8(0.9-3.6)0.0801.6(0.6-4.6)0.35R1 Resection Margin2(1.0-3.9)0.0520.45(0.1-1.8)0.25Failure of Symptom Improvement3.1(1.3-7.2)0.0084.7(1.3-16.6)0.016 Open table in a new tab

MicroRNA dysregulation in adenoid cystic carcinoma of the salivary gland in relation to prognosis and gene fusion status: a cohort study.

Adenoid cystic carcinoma (ACC) is among the most frequent malignancies of the salivary gland, and is notorious for its prolonged clinical course characterized by frequent recurrences often years after initial treatment. No molecular marker has been shown to have independent prognostic value in ACC, including characteristic gene fusions involving MYB, MYBL1, and NFIB. MicroRNA has been shown to be associated with clinical outcome in numerous malignancies, including one study of ACC, warranting further validation of this class of markers in this disease. Here, we investigate the prognostic value of microRNA in two ACC cohorts: a training cohort (n = 64) and a validation cohort (n = 120) with microarray and qPCR. In the training cohort, multivariate analysis of microarray data found high expression of hsa-miR-6835-3p to be associated with reduced recurrence-free survival (RFS) (p = 0.016). Measuring the highest ranking microRNAs identified in survival analysis in the same cohort, qPCR identified high expression of hsa-miR-4676 to be associated with reduced overall survival (OS) and high expression of hsa-mir-1180 to be associated with improved RFS. This was not confirmed in the validation cohort, in which qPCR identified high expression of hsa-mir-21, hsa-mir-181a-2, and hsa-mir-152 to be associated with reduced OS and high expression of hsa-miR-374c to be associated with improved RFS. Interestingly, two distinct subsets of ACC separated in microRNA expression irrespective of gene fusion status, but without significant difference in outcome. Collectively, qPCR identified several microRNAs associated with OS and RFS, and different subsets of ACC separated according to microRNA expression, suggestive of ACC being a heterogeneous group of malignancies in its microRNA profile.