Predictive Value For Recurrence Research Articles

Prognostic Significance of Tumor and Inflammatory Markers in Disease-Free and Overall Survival Duration in Colonic Adenocarcinoma Patients.

Introduction Colorectal carcinoma (CRC) continues to be a major global health concern, contributing substantially to cancer incidence and mortality. Colonic adenocarcinoma, a common subtype of CRC, is influenced by various prognostic factors, including tumor stage, histopathological characteristics, and tumor markers. Despite their routine use in clinical settings, the prognostic value of traditional tumor markers, such as carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and others, is still under debate. In this study, we aim to analyze the tumor markers' prognostic significance in our CRC patients in terms of disease-free survival and overall survival. Methods A retrospective study was conducted on 71 patients who underwent surgery for colonic adenocarcinoma between January 1, 2018, and January 1, 2024. Data on patient demographics, recurrence rates, survival times, and tumor marker levels (CEA, CA 19-9, CA 125, AFP, and CRP to albumin ratio (CAR)), disease-free survival duration (DFS), and overall survival durations (OS) were collected and analyzed. Statistical analyses included Pearson and Spearman correlation coefficients, the Mann-Whitney U test, ROC curve analysis, and Kaplan-Meier survival analysis. Results The study found that elevated CAR and CA 125 levels were significantly associated with higher mortality and recurrence rates, whereas elevated CEA levels were strongly predictive of recurrence. Receiver operating characteristic (ROC) analysis identified optimal cutoff values for these markers, with CEA ≥ 47.145, CA 125 ≥ 15.85, and CAR ≥ 6.796 demonstrating high specificity and predictive value for recurrence. Kaplan-Meier analysis revealed that patients with CEA < 47.145 had a significantly longer DFS (67.7 months) compared to those with CEA ≥ 47.145 (24 months, p < 0.001). Similarly, patients with CA 125 < 15.85 and CAR < 6.796 showed longer DFS compared to those with higher values. Overall survival analysis also highlighted that patients with CA 125 < 21.71 and CAR < 4.09 had better survival outcomes, with significant differences of 26 and 10 months, respectively (p < 0.001 and p = 0.001). Conclusion Tumor markers, such as CEA, CA 125, and CAR, hold significant prognostic value in colonic adenocarcinoma, with higher levels correlating with poorer outcomes. These findings underscore the importance of integrating tumor markers into clinical decision-making to optimize treatment strategies and improve patient survival. Future research should focus on standardizing the use of these markers and exploring novel biomarkers for enhanced prognostication.

Circulating Exosomal microRNA Profiles Associated with Risk of Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps.

Exosomes carry various types of transcripts and serve as promising biomarkers for inflammatory diseases. However, the role of serum exosomal microRNAs (miRNAs) in chronic rhinosinusitis with nasal polyps (CRSwNP) is poorly clarified. A prospective exploratory cohort of 10 CRSwNP patients was conducted, and the serum exosome samples were subjected to miRNA sequencing. Two independent prospective cohorts, consisting of 40 and 54 patients respectively, were recruited from different medical centers for validation. These cohorts were monitored for over two years, with postoperative recurrence serving as the primary outcome measure. The top 3 differentially exosomal miRNAs were validated in the serum samples, and their predictive values for recurrence were assessed. Eight CRSwNP patients completed the follow-up, comprising 4 non-recurrent cases and 4 recurrent cases. Distinctive profiles of serum exosomal miRNAs were identified between the two groups. In the first validation cohort, reverse transcription-polymerase chain reaction results indicated elevated serum exosomal miR-3174 and miR-6750-5p expressions, along with reduced miR-192-3p levels in the recurrence group compared to the non-recurrence group. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis demonstrated significant correlations between expressions of exosomal miR-3174 and miR-192-3p and the risk of postoperative recurrence. These findings were further validated in the second cohort, confirming the elevation of both miRNAs in the recurrence group and their associations with recurrence risk. Additionally, serum exosomal miR-3174 levels increased in recurrent cases compared to their baseline levels. Circulating exosomal microRNA signatures may influence the risk of postoperative recurrence in CRSwNP patients. Serum exosomal elevated exosomal miR-3174 and decreased miR-192-3p were correlated with CRSwNP recurrence risk.

Multiple cytokine analyses identify CSF1 as a robust biomarker for predicting postoperative recurrence in chronic rhinosinusitis with nasal polyps

ObjectiveChronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with a high rate of postoperative recurrence. This study aimed to discover potential biomarkers by analyzing multiple cytokine profiles in serum to predict postoperative recurrence in CRSwNP and to explore the underlying mechanisms. MethodsIn this prospective study, we enrolled 18 healthy controls (HC) and 60 CRSwNP patients and analyzed the baseline serum cytokine profiles using the Luminex assay. Patients were followed up for more than 2 years and divided into non-recurrence and Recurrence groups. The differentially expressed cytokines were validated in the serum and tissue samples in a validation cohort, and their predictive values for recurrence were evaluated. ResultsFifty-four CRSwNP patients completed the follow-up schedule, including 37 patients in the non-Recurrence group and 17 patients in the Recurrence group. Multiple cytokine analyses showed that serum CD40, CD40L, IL-18, IL-8, MCP1, and CSF1 levels were elevated in the CRSwNP group, especially in the Recurrence group, compared to the HC group. Receiver operating characteristic curves (ROC) and Kaplan-Meier survival analysis showed that serum levels of CD40, CD40L, and CSF1 were closely associated with the risk of postoperative recurrence. Further validation results showed that both serum and tissue mRNA levels of CD40, CD40L, and CSF1 were significantly higher in the Recurrence group in comparison with the non-recurrence and HC groups, and tissue CSF1 mRNA expression exhibited a robust value for predicting the CRSwNP recurrence. Immunofluorescence results revealed that CSF1 was enhanced in the recurrent CRSwNP patients, especially in the epithelial cell area, and CSF1 expressions were augmented when patients suffered postoperative recurrence. ConclusionsCirculating cytokine profiles may affect the risk of postoperative recurrence in CRSwNP patients. Our discovery-validation results suggested that CSF1 might serve as a robust biomarker for predicting CRSwNP recurrence.

Expressions of Progesterone Receptor of Orbital Meningiomas in Indonesia.

Visual disturbances that can heal after a complete resection of orbital meningiomas are only about 2.9%. Grading and expression of the progesterone receptor (PR) in orbital meningiomas, according to World Health Organization (WHO) is a useful predictive value of recurrence in the treatment management of orbital meningiomas. This study aims to determine the relationship of PR expression on the grading of orbital meningiomas as tumour prognostic factors. This cross-sectional observational analysis observed 44 orbital meningioma in Cicendo Eye Hospital Bandung and Hasan Sadikin Hospital between 2017-2020. We performed of mRNA PR with RT-qPCR technique and calculation with the 2∆∆Ct formula. Statistical analysis used the Kruskal-Wallis Test, followed by the Mann-Whitney post hoc test with p<0.005. Relative expression of mRNA PR in meningioma orbita grade I to grade III decreased significantly the expression of relative mRNA PR at grade I, II, III of 21.69±44.35, 20.39±26.30 and 1.25±0.85, with Kruskal-Wallis test, p =0.007. Mann Whitney's test results showed relative mRNA PR expression between grades I and II not different (p = 0.055), relative expression mRNA PR between grades I and III differed significantly (p = 0.024), and relative expression mRNA PR between grades I and III was not different (p = 0.638). mRNA PR expression is viable for prognostic value, predicting recurrence and implementing more effective management of subsequent therapy, it must be combined with other markers to determine the nature of the orbital meningioma.

A meta-analysis of the value of circulating tumor cells in monitoring postoperative recurrence and metastasis of colorectal cancer.

Circulating tumor cells (CTCs) as novel biomarkers are widely investigated in various cancers, although most of the literature shows that CTCs have predictive value for recurrence, metastasis, and prognosis after CRC surgery, results remain controversial. We aimed to systematically evaluate the value of CTCs in monitoring of colorectal cancer (CRC) recurrence and metastasis after surgery. The PubMed, Cochrane Library, Embase, and other databases were searched from the establishment of the database to May 27, 2021. Relevant literature searches and data extraction were performed independently by two reviewers. The quality assessment was performed using the QUADAS2 scale developed by the Cochrane collaboration. The heterogeneity was checked using the Spearman correlation coefficient and the Cochran-Q test in the Meta-Disc1.4 software. Subgroup analysis was used to explore the source of heterogeneity. Considering that all the included papers were clinical studies with clinical heterogeneity, random effect model was adopted for analysis. And the sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves of CTCs, in monitoring recurrence and metastasis after CRC, were calculated. The publication bias of the included studies was assessed using Deek's funnel figure. The literature included a total of 13 articles, comprising 1788 cases, and the overall quality of the literature was high. After summing up the indicators, the sensitivity pooled-value of the peripheral blood CTCs to monitor the recurrence and metastasis value of CRC after CRC was 0.67 [95%CI (0.62, 0.71)], specificity pooled-value was 0.71 [95%CI (0.67, 0.72)], PLR pooled-value was 2.37 [95%CI [1.52, 3.71]), NLR pooled into 0.53 [95%CI (0.36, 0.78)], DOR pooled into 4.97 [95%CI (2.11, 11.72)], AUC was 0.7395. Peripheral blood CTCs have a moderate monitoring value for recurrence and metastasis after CRC; CTCs detected one week after surgery may be more correlated with recurrence and metastasis.

Predictive value of ten risk scores for outcomes of atrial fibrillation patients undergoing radiofrequency pulmonary vein isolation

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction: A significant number of patients experience recurrent atrial fibrillation (AF) after ablation. Predicting who will or will not benefit from AF ablation is challenging. Although various risk scores have been designed to predict outcomes after AF ablation, comparative data are sparse and external risk score validation is often lacking. Purpose In this study, we aimed to compare ten previously described risk scores with regard to their predictive value for post-ablation AF recurrence and procedural complications. Methods A total of 482 AF patients (37% non-paroxysmal AF, 66% male, mean age 62 ± 9 years) undergoing initial radiofrequency pulmonary vein isolation (RF-PVI) were included in the present analysis. Prior to ablation, all patients underwent both transthoracic echocardiography and either cardiac computed tomography imaging or cardiac magnetic resonance imaging. The following risk scores were calculated for each patient: APPLE, ATLAS, BASE-AF2, CAAP-AF, CHADS2, CHA2DS2-VASc, DR-FLASH, HATCH, LAGO and MB-LATER. The predictive performance of the risk scores for AF recurrence and complications were assessed separately by receiver operating characteristic (ROC) curves. Results Median follow-up was 16 (12-31) months. AF recurrence after the 90-day blanking period was observed in 199 patients (41%), occurring after a median of 183 (124-360) days after ablation. Overall procedural adverse event rate was 6%. The HATCH score was the only score without predictive value for recurrent AF after ablation (area under curve [AUC] 0.545). All other investigated scores demonstrated statistically significant but poor predictive value for recurrent AF after ablation (AUC 0.553-0.669). CHA2DS2-VASc and CAAP-AF were the only risk scores with predictive value for procedural complications (AUC 0.616, p = 0.043; AUC 0.615, p = 0.044; respectively). ROC curve analyses of the studied risk scores for the prediction of AF recurrence and complications are shown in Figure. Conclusion Currently available risk scores perform poorly in predicting outcomes after RF-PVI. These data suggest that the utility of these scores for clinical decision-making is limited. Abstract Figure. ROC curve analyses of risk scores

Pain in survivors of Ewing sarcoma: Prevalence, associated factors and prediction of recurrence.

While the prognosis of patients with Ewing sarcoma (EwS) is improving, little is known about the frequency of pain and its risk factors in survivors of EwS. This study aims to analyse the prevalence and risk factors of pain and its predictive value for recurrence. In patients with remission after treatment of EwS, frequency and characteristics of pain within the first 5years of follow up were assessed retrospectively. Of 80 patients, 37 (46%) presented with at least one episode of pain. Chronic pain (>3months) was observed in 10 patients (13%). Experience of at least one episode of pain was associated with prior combined local treatment (surgery and radiation compared to surgery alone; odds ratio [OR] 5.83, 95% confidence interval [CI] 1.43-34.9, P=.007). A total of 59 episodes of pain were observed, including 47 acute and 12 chronic episodes. Lower limb pain accounted for 46% (27/59) of all episodes of pain, and was associated with primary tumour of the pelvis or lower extremity (OR 4.29, 95% CI 1.18-18.21, P=.025), which represented 64% (51/80) of all EwS. The positive predictive value of pain for recurrence was only 12%. Pain is a common problem in survivors of EwS, which mostly affects the lower extremity, and should be regularly assessed. Interventions to reduce pain may be particularly important in patients with combined local treatment with surgery and radiation, who seem to be at considerably increased risk for pain. Patients presenting with pain should be examined for recurrence.

Prognostic phenotypic subtypes to predict recurrence and response to adjuvant chemotherapy for colorectal cancer.

205 Background: Histological phenotypic subtypes have been proposed that stratify survival in a discovery cohort of patients with stage I-III colorectal cancer (CRC). However, clinical utility has not been validated nor associations with recurrence and chemotherapy assessed. Therefore, this study assessed prognostic value in patients with stage I-III CRC as well as predictive value for recurrence and chemotherapy response. Methods: Two independent stage I-III CRC patient cohorts were utilized to assess associations between phenotypic subtypes, survival, and recurrence. Stage II-III patients, from the SCOT adjuvant chemotherapy trial, were utilized to assess associations between phenotypic subtypes and adjuvant chemotherapy response. Log rank analysis compared immune and stromal subtypes. Results: In an 867-patient internal cohort, phenotypic subtype stratified patients by disease-free survival (DFS) (HR 2.18 95% CI 2.26-4.47, p &lt; 0.001); independent of stage and location. The stromal subtype also predicted increased local and distant recurrence (p &lt; 0.001). In a 146-patient external validation cohort, phenotypic subtype significantly stratified patients by DFS (HR 3.43 95% CI 1.60-7.35, p = 0.001). In 1343 SCOT trial patients, phenotypic subtype significantly stratified patients by DFS (HR 1.59 95% CI 1.13-2.25, p = 0.010). Furthermore, there was evidence that the effect of regimen depended on phenotypic subtype (p = 0.048), only significantly stratifying DFS in patients receiving FOLFOX (HR 3.73 95% CI 1.58-8.81, p = 0.003) but not CAPOX (HR 0.84 95% CI 0.56-1.26, p = 0.396) adjuvant chemotherapy. Interestingly, the immune subtype associated with improved DFS in patients receiving FOLFOX compared to CAPOX adjuvant chemotherapy (HR 3.40 95% CI 1.41-8.19, p = 0.006). Whereas patients with a stromal subtype trended towards improved DFS in patients receiving CAPOX compared to FOLFOX adjuvant chemotherapy (HR 0.72 95% CI 0.50-1.05 p = 0.088). Conclusions: Histological phenotypic subtypes are an effective independent prognostic classification for patients with stage I-III CRC that can predict response to FOLFOX adjuvant chemotherapy as well as the presence of local and distant recurrence.

Prediction of recurrence and remission within 3years in patients with Cushing disease after successful transnasal adenomectomy.

Some laboratory and clinical features are associated with a probability of recurrence after transnasal adenomectomy for Cushing disease (CD). However, there is no consensus on a set of predictors. Rules for prediction of recurrence were not proposed earlier. To develop prediction model of recurrence/remission after successful neurosurgical treatment for CD. Retrospective single-site comparative study included 349 patients (52 men and 297 women) with a verified diagnosis of CD who underwent effective endoscopic transsphenoidal adenomectomy between 2007 and 2014. Clinical and laboratory parameters were evaluated. Laboratory tests were performed using immunochemiluminescent method. Time-to-event analysis and ROC-analysis were applied. Multivariate models were developed using logistic regression and artificial neural network (ANN). Postoperative cortisol and ACTH levels and their combinations cannot be used for prediction of recurrence. ANN for prediction of recurrence within 3years after successful surgery was developed. Input variables are age, duration of the disease, MRI data on adenoma, morning postoperative levels of ACTH and cortisol, output variable is binary (recurrence/remission). Predictive value for remission is 93%, 95% CI [89%; 96%], and predictive value for recurrence is 85%, 95% CI [71%; 94%]. Web-calculator based on the model is developed and free for use. Effective method for prediction of recurrence and long-term remission within 3years after successful endoscopic transsphenoidal adenomectomy is proposed.

Predicative value of radiomics nomogram based on 18F-FDG PET/CT for the prognosis of patients with postoperative gastric carcinoma

Objective To investigate the clinical value of radiomics nomogram, which is established by 18F-fluorodeoxyglucose (FDG) PET/CT radiomics signature combined with clinical-pathologic risk factors, in predicting the prognosis of patients with postoperative gastric carcinoma. Methods 18F-FDG PET/CT data of 207 patients (143 males, 64 females, age range: 20-85 years) with postoperative gastric carcinoma from January 2008 to August 2015 was reviewed retrospectively. Patients were divided into training group (n=104) and validation group (n=103), and the clinicopathologic information and disease-free survival (DFS) data were acquired. Significant textural features were selected from PET/CT images, and radiomics score (RS) for individual patient was calculated based on the radiomics signatures. The relationship between RS and DFS was analyzed. Cox regression analysis was performed to determine the risk factors of DFS. The radiomics nomogram, obtained from combination of RS with clinicopathologic risk factors, was established and further evaluated in predictive value for recurrence or metastasis of postoperative gastric carcinoma, and the concordance index (C-index) was calculated. Results Cox regression analysis demonstrated that RS, tumor location, depth of invasion, lymph node metastasis, and distant metastasis were the significant risk factors for DFS (hazard ratios: 2.148-2.828, all P<0.05). The radiomics nomogram combined with RS and 4 clinicopathologic risk factors had a better prediction for the estimated DFS, comparing to RS alone. C-index of radiomics nomogram and RS were 0.830 and 0.700 in training group, and 0.776 and 0.681 in validation group, respectively. Conclusion Radiomics nomogram which is established by radiomics signatures and clinicopathologic risk factors may be better for predicting DFS of patients with postoperative gastric carcinoma. Key words: Stomach neoplasms; Prognosis; Positron-emission tomography; Tomography, X-ray computed; Nomograms; Deoxyglucose

Left atrium remodeling predicts late recurrence of paroxysmal atrial fibrillation after second generation cryoballoon ablation

BackgroundAtrial fibrillation (AF) is the most common arrhythmia worldwide. Nowadays, AF ablation is a valuable treatment option. It has been shown that the left atrium (LA) diameter is a predictor of AF recurrence after cryoballoon ablation (CBA). Since it does not reflect the true LA size, we compared the role of different LA anatomical parameters using echocardiography for the prediction of AF recurrence after CBA.MethodsWe retrospectively included 209 patients (mean age 56.1 ± 13.6 years, male 62%) with paroxysmal AF undergoing CBA. A transthoracic echocardiography was performed in all patients.ResultsAt a mean follow-up of 16.9 ± 6.3 months, AF recurred in 25.4% of the patients. LA anterior - posterior diameter (LAD), LA minimum volume (LAmin) and early AF recurrence were independent predictors of recurrence. Based on receiver operating characteristics, cut – off values for LAD and, LAmin were 41 mm, 23.69 mL, respectively. The negative predictive values for recurrence were 73% and 87.3% respectively. In patients with AF recurrence, a significant proportion (30.2%) showed LA longitudinal remodeling (LA superior – inferior diameter) even though classically measured LAD was normal.ConclusionsLongitudinal LA remodeling plays an additional role for predicting AF recurrence after CBA, in patients without LAD dilation. Moreover, LAmin had a high negative predictive value and was an independent predictor of AF recurrence. Therefore, a more complete LA anatomical assessment allows a better prediction of AF recurrences after CBA.

Abstract 3643: Utility of peritoneal and pleural lavages for detection of somatic alterations: A proof-of-concept study

Abstract Background: Surgical resection remains the best treatment option for early-stage endometrial (CE), colorectal (CRC) and lung cancer (LC) patients. However, a proportion of patients (p) develop tumor recurrence, even after curative resection. Peritoneal or pleural lavages may be performed during surgery but little data is available about their potential as liquid biopsies with predictive value for recurrence. This proof-of concept study aimed to determine if somatic mutations can be detected in these lavages. Methods: We analyzed mutations in paired surgical biopsies, blood and peritoneal or pleural lavages supernatants in an early-stage cohort of 25 EC, 12 CRC and 19 LC p. Molecular characterization of surgical biopsies was performed using the GeneReader NGS platform (Qiagen) and the Actionable Insight Tumor Panel, which includes 12 genes (KRAS, NRAS, KIT, BRAF, PDGFRA, ALK, EGFR, ERBB2, PIK3CA, ERBB3, ESR1, and RAF1). cfDNA was purified from blood and lavages using an automatic extractor and the hotspot mutations identified in tumor tissue were tested using a sensitive Taqman assay for codons 12, 13, and 61 in KRAS, codons 542, 545 and 1047 in PIK3CA and codon 600 in BRAF. Results: NGS of tumor biopsies revealed hotspot KRAS, PIK3CA or BRAF mutations in a total of 11/25 (44%) early-stage EC p, 7/12 (58%) early-stage CRC p and 6/19 (32%) early-stage LC p. In peritoneal lavages, hotspot mutations were found in 6/11 (55%) EC p and 2/7 (29%) CRC p and, in pleural lavages, hotspot mutations appeared in 2/6 (33%) LC p. Furthermore, 2/11 (18%) blood samples from EC p, 1/7 (14%) blood samples from CRC p and 1/6 (17%) blood samples from LC p were positive. Conclusions: Our study reveals that mutational analysis in peritoneal or pleural lavages from early stage tumors is feasible and that mutations are more frequently detected in lavages than in blood. Further research will determine if positivity in blood or lavages is associated with early relapse. Citation Format: Núria Jordana Ariza, Mónica Garzón Ibañez, Alejandro Martinez-Bueno, Sonia Gatius Caldero, Clara Mayo de las casas, Ana Velasco, Maria Ruiz, Berta Roman Canal, Jordi Bertran Alamillo, Sonia Rodríguez Muñoz, Raquel Campos Fuentes, Beatriz García, Ariadna Balada Bel, Sergi Villatoro, Miguel Ángel Molina-Vila, Xavier Matias-Guiu. Utility of peritoneal and pleural lavages for detection of somatic alterations: A proof-of-concept study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3643.

Abstract 5243: Prognostic value of nuclear and non-nuclear estrogen receptor expression by immunohistochemistry with phosphor-integrated dots in hormone receptor-positive early breast cancer

Abstract Background: Estrogen receptor α (ERα) is associated to cell proliferation and survival through genomic (nuclear) and non-genomic (non-nuclear) signaling pathway. Endocrine therapy is the most effective therapies for patients with hormone receptor(HR) positive breast cancer. Recent progress shows that both nuclear and non-nuclear crosstalk was considered to contribute to endocrine resistance. Clinically, ERα is predominantly observed using immunohistochemistry(IHC) as a nuclear protein while unable to detect nuclear and non-nuclear ERα separately. Our group recently created new fluorescent nanoparticles called phosphor-integrated dots (PIDs). PIDs has extremely brightness so that it could be double stained with hematoxylin and quantitated without influence. In addition, the localization of biomarker protein can be visualized and analyzed on cell as PIDs score by this method. Methods: 65 HR+/HER2- breast cancer patients from 2001 to 2003 who treated with postoperative endocrine therapy were selected in this study. Expression levels of total ERα, nuclear-ERα, non-nuclear-ERα, progesterone receptor (PR) was examined by IHC with PIDs. Nuclear-ERα was recognized by double staining using hematoxylin. IHC with DAB was carried out to analyze the expression levels of ER and PR and H score was automatically calculated. In addition, PIDs score of non-nuclear-ERα can be calculated through PIDs score of total ERα and nuclear-ERα by PID analyzer. Optimal cutoff value of PIDs score of each receptor to predict survival were derived and independently tested. The correlation among every clinical characteristic and pathological feature was examined. Result: PIDs score of total ERα(χ2=5.17, p=0.023) and nuclear-ERα is negative correlated with relapse (χ2=6.46, p=0.011), ratio of non-nuclear-ERα to total ERα is positive correlated with relapse (χ2=5.82, p=0.016).The cutoff value as 37.46 of nuclear-ERα PIDs score was statistically proved significant for predicting disease-free survival(DFS) (log-rank p=0.020).We also found that cutoff value as 0.32 which represents ratio of non-nuclear-ERα PIDs score to total ERα PIDs score was statistically proved significant for predicting DFS (log-rank p=0.022). H score of ER, PR and PIDs score of non-nuclear-ERα, PR has no predictive value for recurrence. Conclusion: Our result demonstrates that nuclear-ERα PIDs score obtain a higher prognostic value than that of total-ERα PIDs score and H score detected by DAB-IHC. Ratio of non-nuclear-ERα to total ERα may play a role of prognostic factor in HR positive breast cancer. Citation Format: Zhaorong Guo, Hiroshi Tada, Narufumi Kitamura, Yoh Hamada, Shin-ichi Hayashi, Noriaki Ohuchi, Kosuke Gonda, Takanori Ishida. Prognostic value of nuclear and non-nuclear estrogen receptor expression by immunohistochemistry with phosphor-integrated dots in hormone receptor-positive early breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5243.

Survival Outcomes for Patients With Indeterminate 18FDG-PET Scan for Extrahepatic Disease Before Liver Resection for Metastatic Colorectal Cancer

The aim of this study was to evaluate overall survival (OS) and cancer recurrence for patients with indeterminate positron emission tomography (PET) scan for extrahepatic disease (EHD) before liver resection (LR) for colorectal liver metastases (CLMs). Indeterminate EHD as determined by PET imaging indicates a probability of extrahepatic malignancy and potentially excludes patients from undergoing LR for CLM. In a retrospective analysis of prospectively collected data from February 2006 to December 2014, OS for patients with indeterminate EHD on FDG-PET scan before LR for CLM was performed using standard survival analysis methods, including Kaplan-Meier estimator and Cox proportional hazard models for multivariate analyses. Postoperative imaging was used as reference to evaluate the association between indeterminate EHD and recurrence. Of 267 patients with PET scans before LR, 197 patients had no EHD and 70 patients had indeterminate EHD. Median follow-up was 33 months. The estimated 5-year OS was 60.8% versus 59.4% for indeterminate and absent EHD, respectively (P = 0.625). Disease-free survival was comparable between both groups (P = 0.975) and overall recurrence was 57.1% and 59.5% for indeterminate and absent EHD, respectively (P = 0.742). About 16.9% of recurrence was associated with the site of indeterminate EHD, with 80% of associated recurrence occurring in the thorax. The site of indeterminate EHD appears to have a predictive value for recurrence, with indeterminate EHD in the thorax having a higher probability of malignancy. The evidence in this report supports the critical evaluation of PET scan results and that patients are not denied potential curative LR unless the evidence for unresectable EHD is certain.

The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence.

BackgroundThe 2004 World Health Organization classification introduced atypical pituitary adenoma (aPA), which was equivocally defined as invasion with increased mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and extensive p53 immunoreactivity. However, aPAs that exhibit all of these features are rare and the predictive value for recurrence in pituitary adenomas (PAs) remains uncertain. Thus, we sought to characterize pathological features of PAs that correlated with recurrence.MethodsOne hundred and sixty-seven cases of surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St. Mary’s Hospital. Among them, 28 cases were confirmed to be recurrent, based on pathologic or radiologic examination. The pathologic characteristics including mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to recurrence.ResultsAnalysis of the pathologic features indicated that only Ki-67 LI over 3% was significantly associated with tumor recurrence (p = .02). The cases with at least one pathologic feature showed significantly higher recurrence rates (p < .01). Analysis indicated that cases with two pathologic features, Ki-67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly associated with tumor recurrence (p < .01).ConclusionsBased on these results, PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%), or extensive p53 immunoreactivity (≥ 20%). Assessment of these features is recommended for PA diagnosis for more accurate prediction of recurrence.

Prognostic value of total lesion glycolysis on preoperative 18F-FDG PET/CT in patients with uterine carcinosarcoma.

To investigate the relationship between functional tumour parameters measured during preoperative 18F-FDG PET/CT and clinical outcomes in patients with uterine carcinosarcoma. For patients with pathologically proven uterine carcinosarcoma, we determined the maximal and average standardized uptake values, cumulative total lesion glycolysis (TLG) and sum of all metabolic tumour volumes (MTVs). Their predictive value for recurrence and the effects of pretreatment functional tumour activity on patient survival were compared. Clinicopathological data from 28 eligible patients were reviewed. The median duration of progression-free survival was 18.6months (range 6.1-84.5months), and 10 (35.7%) patients experienced recurrences. Univariate analyses showed significant associations between recurrence and tumour size, lymph node metastasis, high TLG and MTV values, and ovarian invasion. Multivariate analysis identified high TLG value as an independent risk factor for recurrence (p = 0.048, hazard ratio 115.261, 95% confidence interval 1.041-12,765.483). Kaplan-Meier survival curves showed that progression-free survival significantly differed in groups categorized according to TLG (p = 0.007, log-rank test). Preoperative TLG measured with 18F-FDG PET/CT was statistically significantly associated with uterine carcinosarcoma recurrence. Metabolic parameters can provide useful quantitative criteria for disease prognostication in patients with uterine carcinosarcoma before treatment. • Preoperative TLG was an independent risk factor for recurrence in uterine carcinosarcoma. • Progression-free survival significantly differed in groups categorized by TLG. • Metabolic parameters can provide useful quantitative criteria for disease prognostication.

The predictive value of electroencephalography in recurrence of the first-ever unprovoked idiopathic seizure

Aim of the study We aimed to study the role of electroencephalography (EEG) and its predictive value for recurrence after the first-ever seizure. Patients and methods Patients who presented with first idiopathic seizure attack were included in this prospective study. The study group included 70 patients (39 male and 31 female). Their ages ranged from 1 to 58 years. All patients included were subjected to history taking and full analysis of the seizure, full neurological examination, routine laboratory tests, neuroimaging, and EEG evaluation, and then all patients were interviewed monthly for 3 successive months. Results Sixteen patients (23%) had focal seizures and 54 patients (77%) had generalized seizure. Nocturnal seizures were found in 45.7% of patients, whereas diurnal seizures were found in 54.3% patients. Aura was recorded in 17% of cases, whereas postictal state (confusion, headache, muscle ache, and Todd’s paralysis) occurred in 60% of cases. Past history of febrile seizures was present in 17% of cases, family history of epilepsy was positive in 10% of cases, and 31.4% of cases had positive consanguinity. Abnormal EEG was found in 54.3% of patients [31.4% of patients had generalized epileptiform discharge, 15.7% of patients had focal epileptiform discharge with or without secondary generalization, and 7.2% of patients had no specific changes (focal or generalized slowness)] and lastly normal EEG was found in 45.7% of patients. After 3 months of follow-up, 37 patients (52.9%) had recurrence of seizure: 75.6% of patients had generalized seizures and 24.4% of patients had focal seizures. The percent of recurrence among patients with abnormal EEG was 70.3% and that among those with normal EEG was 29.7%. As regards EEG findings, there were a significant correlation between abnormal EEG and generalized epileptiform discharge and recurrence of seizure. Conclusion EEG, especially during the first 48 h after seizure, had a prognostic value for recurrence of seizure.

Positive predictive value of CEA and Ca19-9 as tumor markers for recurrent colorectal cancer in cases where conventional work-up fail to localize disease.

Introduction: Routine surveillance of colorectal cancer includes serial measurements of CEA levels. Although not routinely indicated Ca 19-9 is also a tool for recurrence. When any of these serum markers is elevated during follow up, this could represent a recurrence. The management of elevated tumor marker levels include clinical exams, endoscopy and conventional imaging –ultrasound, CT, MRI.Objective: To evaluate the positive predictive value of CEA and Ca19-9 as tumor markers for recurrent colorectal cancer in cases where conventional imaging and endoscopic studies fail to localize disease.Materials and methods: A total of 75 patients with elevated CEA and/or Ca19-9 serum levels and negative endoscopic exam as well as negative abdominal CT and Chest X-ray were included in the study. CEA levels were tested in 50 patients. Ca 19-9 was tested in 65 patients. 34 of the patients had both markers tested. All patients underwent whole body 18F-FDG PET/CT. Patients with negative of equivocal PET scan were further followed up (10 to 24 months).Results: Based on the reference standard – the results from PET/CT, if positive and the results from follow-up in cases of negative or equivocal scans, the positive predictive value of Ca 19-9 was 84% and that of CEA -83%. There was no significant difference in the PPV of Ca19-9 and CEA.Conclusion: Elevated CEA and Ca 19-9 levels in patients under active surveillance after operation for colorectal cancer have high positive predictive value for recurrence, even in cases where conventional work-up – endoscopy and CT don’t localize disease.

Low P-wave amplitude (

We hypothesized that P-wave amplitude in lead I is related to left atrial (LA) remodelling and inter-atrial conduction pattern, and has a predictive value for recurrence after radiofrequency catheter ablation (RFCA) among patients with paroxysmal atrial fibrillation (PAF). A total of 525 consecutive patients with PAF (76% male, 56 ± 12 years old) who underwent RFCA were included. We compared pre-procedural sinus rhythm electrocardiograms without antiarrhythmic drug effect with LA volume (CT), LA voltage (NavX), the earliest activation site (EAS) conduction pattern of LA, and clinical recurrence rate. P-wave amplitude in lead I was significantly lower in patients with recurrence than in those that remained in sinus rhythm (P < 0.001) during 21 ± 10-month follow-up. P-wave amplitude in lead I was linearly correlated with LA voltage (β = 2.52, 95% CI 0.606-4.425, P = 0.010), LA conduction velocity (β = 1.91, 95% CI 0.941-2.876, P < 0.001), and low septal displacement of EAS (β = -1.67, 95% CI -2.352 to -0.996, P < 0.001). P-wave amplitudes <0.1 mV in lead I were independently associated with clinical recurrence of AF on multivariate Cox regression analysis (adjusted HR 2.163, 95% CI 1.307-3.581, P = 0.003). The integrated area under the curves was 0.705 (95% CI 0.655-0.755). Low P-wave amplitude (<0.1 mV) in lead I is related to LA remodelling and displaced inter-atrial conduction pattern to low septum, and independently predicts clinical recurrence after RFCA in patients with PAF.

Textural features in pre-treatment [F18]-FDG-PET/CT are correlated with risk of local recurrence and disease-specific survival in early stage NSCLC patients receiving primary stereotactic radiation therapy.

BackgroundTextural features in FDG-PET have been shown to provide prognostic information in a variety of tumor entities. Here we evaluate their predictive value for recurrence and prognosis in NSCLC patients receiving primary stereotactic radiation therapy (SBRT).Methods45 patients with early stage NSCLC (T1 or T2 tumor, no lymph node or distant metastases) were included in this retrospective study and followed over a median of 21.4 months (range 3.1–71.1). All patients were considered non-operable due to concomitant disease and referred to SBRT as the primary treatment modality. Pre-treatment FDG-PET/CT scans were obtained from all patients. SUV and volume-based analysis as well as extraction of textural features based on neighborhood gray-tone difference matrices (NGTDM) and gray-level co-occurence matrices (GLCM) were performed using InterView Fusion™ (Mediso Inc., Budapest). The ability to predict local recurrence (LR), lymph node (LN) and distant metastases (DM) was measured using the receiver operating characteristic (ROC). Univariate and multivariate analysis of overall and disease-specific survival were executed.Results7 out of 45 patients (16%) experienced LR, 11 (24%) LN and 11 (24%) DM. ROC revealed a significant correlation of several textural parameters with LR with an AUC value for entropy of 0.872. While there was also a significant correlation of LR with tumor size in the overall cohort, only texture was predictive when examining T1 (tumor diameter < = 3 cm) and T2 (>3 cm) subgroups. No correlation of the examined PET parameters with LN or DM was shown.In univariate survival analysis, both heterogeneity and tumor size were predictive for disease-specific survival, but only texture determined by entropy was determined as an independent factor in multivariate analysis (hazard ratio 7.48, p = .016). Overall survival was not significantly correlated to any examined parameter, most likely due to the high comorbidity in our cohort.ConclusionsOur study adds to the growing evidence that tumor heterogeneity as described by FDG-PET texture is associated with response to radiation therapy in NSCLC. The results may be helpful into identifying patients who might profit from an intensified treatment regime, but need to be verified in a prospective patient cohort before being incorporated into routine clinical practice.