Adverse Prognostic Factor In Patients Research Articles

Comorbid thrombosis as an adverse prognostic factor in patients with ovarian clear cell carcinoma regardless of staging.

Patients with ovarian clear cell carcinoma (OCCC) often present with thrombosis. While cancer patients with concomitant thrombosis were generally reported to have worse prognoses than those without, the association between thrombosis and prognosis has not been elucidated in OCCC. This study aimed to determine how the co-occurrence of thrombosis affects OCCC prognoses. We retrospectively examined 115 patients with OCCC who were diagnosed and treated at the University of Tokyo Hospital between 2009 and 2019. Of 115 patients with OCCC, thrombosis was present in 12.5% of 80 patients and in 42.8% of 35 patients who had OCCC stage I/II and stage III/IV, respectively. In stage I/II, the 5-year progression-free survival was 20.6% and 91.8% among patients with thrombosis and among those without, respectively, while the corresponding 5-year overall survival rates were 50.0% and 94.1%. Therefore, the outcomes were significantly poorer among patients with thrombosis (p < 0.0001 and p < 0.0001, respectively). In stage III/IV, the 5-year progression-free survival was 26.7% and 52.8% among patients with thrombosis and among those without, respectively, while the corresponding 5-year overall survival rates were 32.0% and 62.2%. Similarly, the outcomes were significantly poorer among patients with thrombosis (p = 0.0139 and p = 0.369, respectively). We determined that thrombosis is more likely to develop in advanced OCCC stages than in early stages, and its co-occurrence is associated with a poor prognosis, regardless of disease stage.

Renal Sub-Study (GEM-KyCyDex): Cystatin C Improves the Proficiency of Creatinine Alone in the Detection and Management of Myeloma-Related Renal Impairment

Introduction: Renal impairment is an important adverse prognostic factor in patients with multiple myeloma (MM), which limits the use of certain drugs that require dose adjustment. Renal function is measured by the glomerular filtration rate (GFR) which is estimated with equations such as MDRD or CKD-EPI. In clinical practice, serum creatinine (Crea) is the main parameter used in these calculations, however, the recent IMWG recommendations suggest including other parameters such as Cystatin C (CC) to improve the management of kidney disease in patients with MM. AIM: To assess the prevalence of renal impairment in patients with multiple myeloma at relapse (MMRR), comparing the GFR (CKD-EPI), using Crea alone or including also CC in the equation and to study the potential association with the prognosis. Material and methods: Within the phase II GEM-KyCyDex clinical trial, which compared carfilzomib and dexamethasone in combination with cyclophosphamide (KCd) versus carfilzomib and dexamethasone (Kd) in MMRR, a substudy was conducted to analyze in detail the basal renal function and its potential modification during 12 months of follow-up, using CC and Crea to estimate GFR Results: 87 patients were included in the renal substudy (45KCd/42Kd) with a median age of 70 years (40-89 range) and 45% were women. The mean Crea level was 1.06 mg/dL (± 0.36) (normal range 0.7-1.4 mg/dLin men and 0.6-1.2 mg/dL in women). and the mean CC was 1.43 mg/L (± 0.46) (normal range 0.62-1.11 mg/L). Progressive elevations of CC were present as ISS stages increase and according to the elevations of beta2microglobulin, and patients with ISS-1 stage had lower CC levels than patients with ISS-3 stage (1.13 vs 1.63 mg/L. p= 0.001), while Crea levels did not show significant differences (p= 0.62). According to method for estimating GFR that includes the CC and Crea parameters (CKD-EPI Crea-CC), the prevalence of patients at baseline with GFR &amp;lt; 60 mL/min, adjusting for body surface area, was 45% versus 24% detected by the CKD-EPI that only includes creatinine. Interestingly, slight reductions in both CC and Crea levels were observed throughout treatment, from baseline to the end of cycle 12 (median of 1.42 mg/L vs 1.07 for CC and 1.23 mg/dL vs 0.7 for crea), although differences were not statistically significant. When studying the association with response, those patients who maintained an abnormal kappa/lambda free light chain ratio, had higher CC levels (1.51 mg/L). compared to patients who presented a normal ratio (1.33 mg/L). However, in the case of Crea, the values remain within the normal range (1.11 mg/dL) The equation that presented the greatest diagnostic capacity (according to ROC curves) in terms of detecting patients who dropped off the study due to toxicity or progression, was the CKD-EPI CC formula with baseline values lower than 54 mL/min (AUC 0.59 (0.44-0.72, 95% CI), with a sensitivity/specificity of 68/71% respectively. In these same patients, the CKD-EPI equation did not identify renal impairment, since values higher than 62 mL/min (AUC 0.51 (0.37-0.66, 95% CI)) presented the worst prognosis. Conclusions: In the patients included in the renal substudy of the phase II GEM-KyCyDex clinical trial, we observed a prevalence of chronic kidney disease with the CKD-EPI CC-crea equation of 45%, being 21% of them hidden (not detected by creatinine alone). Patients with elevated CC were found mainly in the stage with the worst prognosis ISS-3, they showed a more altered kappa/lambda ratio and a worse prognosis in terms of showing greater toxicity or abandonment of the study due to disease progression, situations not detected with elevations of crea. CC can improve monitoring of patients with MM, to early detect renal impairment and patients with the worst prognosis who will require close monitoring

Long-term mortality risk of valvular heart disease adults over 35 years old in Chinese communities

Objective: To investigate the risk and influencing factors of long-term mortality of valvular heart disease (VHD) adults aged 35 years and over in Chinese communities. Methods: A cohort study was carried out. The data of the subjects who underwent echocardiography were collected from the Chinese Hypertension Survey between 2012 and 2015 and survival outcomes were followed up between 2018 and 2019. Kaplan-Meier survival curves were plotted and compared using log-rank test. Cox proportional hazards models were used to analyze the influence of VHD on mortality. Results: During an average follow-up time of (4.6±0.9) years, a total of 23 237 participants (10 881 males and 12 356 females) were pooled into the final analysis from 5 eastern, 5 central, and 4 western provinces, cities and autonomous regions in China, with a mean age of (56.9±13.2) years. Among the included participants, 1 004 had VHD (467 males and 537 females), with a mean age was of (68.1±12.6) years. In the Kaplan-Meier analysis, participants with VHD had a significantly increased risk of all-cause mortality (log-rank χ2=351.82, P<0.001) and cardiovascular mortality (log-rank χ2=284.14, P<0.001) compared with those without VHD. Multivariate Cox regression analysis showed that compared with those without VHD, the participants with rheumatic VHD had a 45% increased risk of all-cause mortality (HR=1.45, 95%CI: 1.12-1.89) and degenerative VHD increased the risk of cardiovascular mortality by 69% (HR=1.69, 95%CI: 1.19-2.38). The risk factors of cardiovascular mortality for VHD were age 55 years and over (55-<75 years: HR=4.93, 95%CI: 1.17-20.85;≥75 years: HR=11.92, 95%CI: 2.85-49.80) and diabetes mellitus (HR=1.71, 95%CI: 1.00-2.93). Conclusions: VHD is a risk factor of all-cause mortality and cardiovascular mortality among adults aged 35 years and over. Age 55 years and over and diabetes mellitus are adverse prognostic factors for patients with VHD.

Prognostic significance of mean corpuscular volume in patients with pancreatic ductal adenocarcinoma and multimodal treatment

Mean corpuscular volume (MCV) has shown mounting evidence as a prognostic indicator in a number of malignancies. The aim of this study was to examine the prognostic potential of pretherapeutic MCV among patients with pancreatic ductal adenocarcinoma (PDAC) who underwent upfront resection or resection after neoadjuvant treatment (NT). Consecutive patients with PDAC who underwent pancreatic resection between 1997 and 2019 were included in this study. Neoadjuvantly treated patients' serum MCV was measured before NT and before surgery. In patients undergoing upfront resection serum MCV was measured before surgery. Median MCV values were used as cut-off to distinguish high from low MCV values. Five hundred and forty-nine (438 upfront resected and 111 neoadjuvantly treated) patients were included in this study. Multivariate analysis revealed, that high MCV before and after NT, were independent negative prognostic factors for overall survival (P<0.01, respectively). Furthermore, the median MCV value from before to after NT increased significantly (P<0.001, Wilcoxon signed-rank test) and was (P=0.03, Wilcoxon rank sum test) associated with tumor response to NT. High MCV is an independent adverse prognostic factor in patients with resectable neoadjuvantly treated PDAC and may qualify as useful indicator to help physicians to provide personalized prognostication.

Impact of systemic immune-inflammation index in patients with limited-stage small cell lung cancer.

e20626 Background: The systemic immune-inflammation index (SII) has been suggested as a prognostic marker in several solid malignant neoplasms. However, there are few studies on the prognostic value of SII in patients with limited-stage SCLC. This study explored the impact of SII on overall survival (OS) and progression-free survival (PFS) in patients with limited-stage small cell lung cancer, and compared the predictive ability of SII and platelet/lymphocyte ratio (PLR) to find a better prognostic marker. Methods: In total, 572 patients with new diagnosis of limited-stage SCLC were included in this study. The optimal threshold of SII and PLR were determined using the outcome(OS)-based method by maximizing the log-rank test statistic and the survival differences.The predictive ability of SII and PLR were compared by drawing the continuous time-dependent receiver operating characteristic curves (time-dependent ROC). Logistic multivariable analysis was performed to identify factors associated with high SII. Propensity score matching (PSM) was used to balance confounders between groups and adjust observed selection bias. Kaplan-Meier methods and Cox proportional hazards models were used to assess the impact of pre-treatment SII on OS and PFS. Results: The median age of the whole group was 60.0 (25.0-81.0) years, and the median follow-up time was 56.5 (2.5-95.4) months. The optimal cutoff value of SII and PLR were 760.6 and 137.3, respectively. The area under the time-dependent ROC curves of SII and PLR in 1-, 2- and 3-year were 0.727, 0.708, 0.680 and 0.680, 0.669, 0.649, respectively. The high SII group was correlated with pleural effusion (P = 0.001), T stage (P = 0.009), N stage (P = 0.048), and pretreatment serum sodium (P = 0.003). The median OS and PFS of the whole group was 26.0 months (95%CI 23.8-28.2) and 13.0 months (95%CI 11.3 -14.7), and the 1-, 3-, 5-year OS rates and the 1-, 3-, 5-year PFS rates were 81.1%, 35.5%, 27.1% and 52.8%, 24.8%, 19.9%, respectively.There were 414 patients after PSM. In multivariable survival analysis, SII remained an independent prognostic factor for OS (HR1.792; 95%CI 1.416-2.268; P &lt; 0.001) and PFS (HR1.410; 95%CI 1.043-1.906; P = 0.025). Conclusions: Elevated SII is an independent adverse prognostic factor in patients with limited-stage SCLC and is superior to PLR in terms of prognostic ability.

Prognostic Analysis of Lymphovascular Invasion in Stages I-III Colorectal Cancer: A Retrospective Study Based on Propensity Score Match.

Lymphovascular invasion (LVI) is a micropathological tumor factor believed to increase the risk of tumor metastasis and spread. Propensity score matching (PSM) is a statistical method that can control confounding factors. Current research rarely considers the confounding relationship between LVI and other factors that may influence prognosis. This study aimed to investigate the relationship between LVI and prognosis in patients with stage I-III colorectal cancer (CRC) by using propensity score matching (PSM). This was a retrospective study involving 610 patients. PSM was used to adjust for baseline differences between the groups. The survival rates were calculated. A nomogram was constructed based on the Cox proportional hazards model before matching. The C-index, receiver operating characteristic curve (ROC), and calibration curve were used to evaluate the nomogram. A total of 150 patients tested positive for LVI, accounting for 24.6% of the total, and 120 couples of patients were identified after PSM. The survival curve and Cox proportional hazards model after matching confirmed the adverse effects of LVI on tumor prognosis. The Cox proportional hazards model before matching showed that age, carcinoembryonic antigen level, T stage, N stage, histologic grade and LVI were independent prognostic factors. The C-index of the nomogram established based on the Cox proportional hazards model was 0.787 (95% CI=0.728-0.845). The areas under the curve were 0.796 in the 3-year ROC. LVI is an adverse prognostic factor in patients with stage I-III colorectal cancer.

Defining subventricular zone involvement to predict the survival of patients in isocitrate dehydrogenase-wild type glioblastoma: validation in a prospective registry.

The prognostic value of subventricular zone distance (SVD) is unclear because of different definitions and lack of evaluation of clinical survival models. The aim of this study was to define SVD and evaluate its prognostic value in a survival nomogram for glioblastoma. This retrospective study included 158 (SVD biomarker) from historical glioblastoma patients and 187 (survival modeling) with IDH-wild type glioblastoma from a prospective registry (NCT02619890). SVD was assessed by two radiologists: definition 1, the distance between the tumor edge to subventricular zone (SVZ); definition 2, the distance between the tumor centroid to SVZ; definition 3, enhancement at the ventricular wall. The associations between SVD and overall survival (OS) were evaluated using multivariable Cox proportional hazards regression analysis. Performance of an updated SVD survival model was compared with that of the Radiation Therapy Oncology Group (RTOG) 0525 nomogram. SVD according to both definition 1 (hazard ratio [HR]: 0.97, 95% CI: 0.94-0.99; p = .011) and definition 2 (HR: 0.96, 0.94-0.98, p < .001) was adversely associated with OS. Definition 1 was adversely associated with PFS (HR: 0.96, 0.94-0.99, p = .008) and showed the highest reproducibility (intraclass correlation coefficient, 0.90). The SVD-updated model showed similar to better performance than the RTOG model for predicting OS of up to 3years (AUC: 0.735-0.738 vs. 0.687-0.708), with higher time-dependent specificity for 1-year (89.9% vs. 70.6%) and 3-year OS (93.3% vs. 80.0%). SVZ distance is an independent adverse prognostic factor in patients with IDH-wild type glioblastoma. Updating the survival model with SVZ provides better time-dependent specificity and reproducibility. •Subventricular zone distance (SVD) measurement from tumor edge showed high reproducibility. •Longer SVD was independently associated with longer overall survival. •Adding SVD improved time-dependent specificity for survival model in a prospective registry.

Metabolic Tumor Volume Measured by 18F-FDG PET/CT is Associated with the Survival of Unresectable Hepatocellular Carcinoma Treated with PD-1/PD-L1 Inhibitors Plus Molecular Targeted Agents.

The combination of PD-1/PD-L1 inhibitors and molecular targeted agents showed promising efficacy for unresectable hepatocellular carcinoma (uHCC). This study aimed to investigate the prognostic value of metabolic parameters from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in patients with uHCC underwent the combined therapies. Patients with uHCC treated with a combination of immunotherapy and targeted therapy who underwent baseline 18F-FDG PET/CT between July 2018 and December 2021 were recruited retrospectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake values (SUVmax), and clinical and biological parameters were recorded. A multivariate prediction model was developed for overall survival (OS) using these parameters together with clinical prognostic factors. Seventy-seven patients were finally included. The median OS was 16.8 months. We found that a high MTV (≥39.65 cm3 as the median value) was significantly associated with OS (P<0.05). In multivariate analyses for OS, a high MTV, high Eastern Cooperative Oncology Group performance status (ECOG-PS, ≥1), Child-Pugh (B-C) grade, and the presence of bone metastasis were significantly associated with poor OS (HR 1.371, HR 3.73, HR 15.384, and HR 2.994, all P<0.05, respectively). A multivariate prognostic model including MTV and prognostic factors, such as ECOG-PS, Child-Pugh grade, and bone metastasis, further improved the identification of different OS subgroups. High MTV is an adverse prognostic factor in patients with uHCC treated with a combination of immunotherapy and molecular targeted agents. Integrating PET/CT parameters with clinical prognostic factors could help to personalize immunotherapy.

Decreased transthyretin predicts a poor prognosis in primary myelodysplastic syndrome.

This study aims to investigate the prognostic significance of transthyretin in newly diagnosed myelodysplastic syndromes (MDS). The clinical, laboratory, and follow-up data of 280 newly diagnosed patients with MDS were collected. The relationship between serum transthyretin levels and overall survival (OS) and leukemia-free survival (LFS) were analyzed by Kaplan-Meier analysis and Cox Regression Model. In the MDS cohort, there were 121 cases in the low transthyretin group and 159 cases in the normal transthyretin group. MDS patients with decreased transthyretin had a higher risk score on the Revised International Prognostic Scoring System (IPSS-R) (p = 0.004) and on the molecular IPSS (IPSS-M) (p = 0.005), a higher frequency of TP53 mutation (p < 0.0001), a shorter OS (p < 0.0001) and LFS (p < 0.0001). Multivariate analyses showed that higher IPSS-R and IPSS-M score were adverse factors for OS (p = 0.008 and p = 0.015, respectively) and LFS (p = 0.024 and p = 0.005, respectively). Mutations of TP53 and NRAS were also poor factors for LFS (p = 0.034 and p = 0.018, respectively). Notably, decreased transthyretin was an independent adverse predictor for OS (p = 0.009, HR = 0.097, 95%CI, 0.017-0.561) but not for LFS (p = 0.167) when IPSS-R was included in the Cox regression model and an independent poor one for OS (p = 0.033, HR = 0.267, 95%CI, 0.080-0.898) and LFS (p = 0.024, HR = 0.290, 95%CI, 0.099-0.848) while IPSS-M involved. The results indicate that decreased transthyretin could be an independent adverse prognostic factor in patients with MDS and may provide a supplement to IPSS-R and IPSS-M.

Abstract GS3-09: GS3-09 Circulating Tumor Cells-driven choice of first line therapy for ER+ HER2- metastatic breast cancer: overall survival analysis of the randomized STIC CTC trial

Abstract Background: High circulating tumor cell (CTC) count (CTChigh) is a strong adverse prognostic factor in patients with metastatic breast cancer (mBC). In the STIC CTC trial (NCT01710605), run before the introduction of CDK4/6 inhibitors for ER+/HER2- mBC, we showed that CTC count (CTC arm) was non inferior to clinician’s choice (standard arm) on progression-free survival (PFS) to guide first line treatment selection between chemotherapy (CT) and endocrine therapy (ET) (Bidard et al., JAMA Oncol 2021). Of note, patients who had treatment escalated from ET (a priori clinician choice) to CT in the CTC arm, had a significantly longer PFS. We report here overall survival (OS) results of this multicenter CTC clinical utility trial. Methods: In the CTC arm, N=377 patients had their treatment determined by baseline CTC count: CT if CTChigh (≥5 CTCs/7.5 mL, CellSearch®), ET if CTClow. In the standard arm (N=378 patients), the choice was left to the investigator: CT if clinical high risk (Clinhigh), ET if clinical low risk (Clinlow). Therefore, patients with discordant Clinlow/CTChigh or Clinhigh/CTClow profiles had their first line treatment escalated from ET (standard arm) to CT (CTC arm) or de-escalated from CT (standard arm) to ET (CTC arm), respectively. Patients with concordant Clinlow/CTClow and Clinhigh/CTChigh profiles received ET and CT in both arms, respectively. Results: Among 755 randomized patients, N=189 (25.0%) had a Clinlow/CTChigh profile, N=103 (13.6%) Clinhigh/CTClow, N=363 (48.2%) Clinlow/CTClow and N=100 (13.2%) Clinhigh/CTChigh. OS was analyzed after a median follow-up of 57 months and 382 events (50.6%). In the Clinlow/CTChigh subgroup, CT in the CTC arm led a longer OS (mOS: 51.8 months [43.3-NR]) than ET in the standard arm (35.4 months [30.4-45.4]; HR=0.53 [0.36-0.78], p=0.001). In patients Clinhigh/CTClow, no significant difference was observed whether they received CT (standard arm) or ET (CTC arm) (45.9 months [36.3-59.8] vs 49.4 months [35.4-65.4]; HR=0.88 [0.51-1.51], p=0.63). Pooling the two discordant groups (Clinlow/CTChigh or Clinhigh/CTClow), the CTC-driven strategy was superior to the clinician-driven treatment decision (HR=0.63 [0.46-0.86], p=0.02). Pooling all concordant and discordant groups together, a median OS of 45.5 (95%CI=[40.9-51.1]) and 51.3 months [46.8-55.1] was observed in the standard and CTC arms, respectively (HR=0.84 [0.69-1.03], p=0.10). Conclusions: Prognostic information brought by CTC or standard factors is discordant in 40% of patients with ER+ HER2- mBC. In case of a discordant estimate, the STIC CTC trial shows the superiority on OS of the CTC-driven treatment decision strategy. These results also suggest a possible clinical utility of CTC to adjust systemic treatment for mBC in second and later lines, after progression on CDK4/6 inhibitors. Funding:The study was funded by Institut Curie; the French National Cancer Institute (INCa), as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011 (STIC 2011); and Menarini Silicon Biosystems (Castel Maggiore, Italy). Citation Format: Francois-Clement Bidard, Nicolas Kiavue, Catherine Alix-Panabières, Sylvain Dureau, Thomas Bachelot, Hugues Bourgeois, Anthony Gonçalves, Etienne Brain, Sylvain Ladoire, Florence Dalenc, Joseph Gligorov, Luis Teixeira, George Emile, Jean-Marc Ferrero, Delphine Loirat, Luc Cabel, Véronique Diéras, Frédérique Berger, William Jacot, Jean-Yves Pierga. GS3-09 Circulating Tumor Cells-driven choice of first line therapy for ER+ HER2- metastatic breast cancer: overall survival analysis of the randomized STIC CTC trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS3-09.

Association of Phase Angle with Overall Survival in Patients with Cancer: A Prospective Multicenter Cohort Study

Low phase angle (PhA) is related with poor clinical status of cancer patients. The objective of this study was to establish sex- and age-specific cutoff points and examine the association between PhA and overall survival (OS) in Chinese cancer patients. This cohort study included data on 1,814 patients with cancer from December 2013 to October 2020. The association between low PhA and overall survival was analyzed using the Kaplan-Meier method and Cox regression model. Among 1,814 participants, there were 993 (54.70%) male and 821 (45.30%) female patients. The optimal cutoff points of low PhA were 4.8°, 4.2°, 4.4°, and 3.8° for the young male, elderly male, young female, and elderly female, respectively. Low PhA was independently associated with poorer OS in young female, elderly female and male (HR: 1.59, 95% CI: 1.08-2.34; HR: 1.65, 95% CI: 1.03-2.67; HR: 2.00, 95% CI: 1.45-2.75). In addition, low PhA was demonstrated to be an adverse prognostic factor in patients with lung cancer, colorectal cancer, and esophagus cancer (HR: 1.85, 95% CI: 1.39-2.47; HR: 2.05, 95% CI: 1.13-3.70; HR: 2.92, 95% CI: 1.49-5.71). Based on cutoff points, low PhA was associated with worse prognosis in patients with cancer.

Computed Tomography-Defined Sarcopenia in Outcomes of Patients with Unresectable Hepatocellular Carcinoma Undergoing Radioembolization: Assessment with Total Abdominal, Psoas, and Paraspinal Muscles

Introduction: Sarcopenia is an adverse prognostic factor in patients with liver cirrhosis and hepatocellular carcinoma (HCC). Image-based sarcopenia assessment allows a standardized method to assess abdominal skeletal muscle. However, which is an index muscle for sarcopenia remains unclear. Therefore, we investigated whether sarcopenia defined according to different muscle groups with computed tomography (CT) scans can predict the prognosis of HCC after radioembolization. Methods: In this retrospective study, we analyzed patients who underwent radioembolization for unresectable HCC between January 2010 and December 2019. Before treatment, the total abdominal muscle (TAM), psoas muscle (PM), and paraspinal muscle (PS) areas were evaluated using a single CT slice at the third lumbar vertebra. In previous studies, sarcopenia was determined using the TAM, PM, and PS after stratifying by sex. Finally, we investigated each muscle-defined sarcopenia to decide whether or not it can serve as a prognostic factor for overall survival (OS). Results: We included 92 patients (74 men and 18 women). TAM, PM, and PS areas were significantly higher in the men than in the women (all p < 0.05). The patients with sarcopenia defined using PM, but not TAM and PS, exhibited significantly poorer OS than those without sarcopenia (median 15.3 vs. 23.8 months, p = 0.034, 0.821, and 0.341, respectively). After adjustment for clinical variables, such as body mass index, liver function, alpha-fetoprotein level, clinical staging, treatment response, and posttreatment curative therapy, PM-defined sarcopenia (hazard ratio: 1.899, 95% confidence interval: 1.087–3.315) remained an independent predictor for the poor OS. Conclusion: CT-assessed sarcopenia defined using PM was an independent prognostic factor for the poorer prognosis of unresectable HCC after radioembolization.

Characterization of the tumour microenvironment phenotypes in malignant tissues and pleural effusion from advanced osteoblastic osteosarcoma patients.

Malignant pleural effusion (MPE) is an adverse prognostic factor in patients with osteoblastic osteosarcoma; however, the cellular contexts of MPE are largely unknown. We performed single-cell RNA-sequencing (scRNA-seq) on 27260 cells from seven MPE samples and 91186 cells from eight osteosarcoma tissues, including one recurrent, one lung metastasis and six primary tumour (PT) samples, to characterize their tumour microenvironment. Thirteen main cell groups were identified in osteosarcoma tumour and MPE samples. Immune cells dominate the cellular contexts in MPE with more T/NK cells and less osteoclasts compared to PT samples. Of T/NK cells, CD8+ GNLY+ , CD8+ KLRC2+ T cells and FCGR3A+ NK cells were enriched in MPE but CD4+ FOXP3+ Tregs were enriched in PT samples. Naïve IGHD+ B and immune regulatory IGHA1+ B cells were largely identified in MPE, whereas bone metabolism-related CLEC11A+ B cells were significantly enriched in osteosarcoma PT. M2-type TAMs, including CLEC11A_TAM, C1QC_TAM and Prolif_TAMs, among myeloid cells were enriched in PT, which may suppress cytotoxicity activities of T cells through multiple ligand-receptor interactions. Mature LAMP3+ DCs were transformed from CD1C+ DC and CLEC9A+ DC sub-clusters when exposure to tumour alloantigens, which may improve T cell cytotoxicity activities on tumour cells under anti-PD-L1 treatments. In further, immune cells from MPE usually present up-regulated glycolysis and down-regulated oxidative phosphorylation and riboflavin metabolism activities compared to those in PT samples. Our study provided a novel cellular atlas of MPE and PT in patients with advanced osteosarcoma, which may provide potential therapeutic targets in the future.

ALL-228 Unfavorable Influence of Minimal Residual Disease on the Outcome of Allogeneic Hematopoietic Cell Transplantation in Acute Lymphoblastic Leukemia in the First Remission

Persistence of minimal residual disease (MRD) is the most important adverse prognostic factor for patients with acute lymphoblastic leukemia (ALL), irrespective of classical risk factors identified at onset. Detection of MRD in the post-induction phase of ALL treatment is the only generally accepted risk factor that is considered a direct indication for inclusion in the treatment of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several studies in recent years have shown that MRD determined before transplantation may increase the risk of disease relapse in ALL patients. To assess the impact of pre-transplant MRD status determined by multiparameter flow cytometry (MFC) on the long-term results of allo-HSCT in ALL patients. The study involved 98 patients with ALL in the 1st CR (n=58) and 2nd or 3rd CR (n=40) who underwent allo-HSCT in our center from November 2015 to July 2021. The median follow-up was 11.7 (1-65.5) months. To determine MRD, 12-color MFC was performed on bone marrow samples obtained before allo-HSCT. The probabilities of OS and DFS and the probability of relapse (PR) were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to assess the influence of various independent factors (donor type, conditioning regimen, graft source, GVHD prophylaxis, pre-transplant MRD status, age) on PR. Ten patients in 1st CR and 14 patients in 2nd or 3rd CR were identified as MRD+ before allo-HSCT. OS of MRD+ patients in 1st CR did not significantly differ from MRD- patients, although it was worse (28% vs. 78%, P=0.09). Significant differences were found in the DFS of MRD+ and MRD- patients (20% vs. 56%, P=0.0317); PR was also significantly higher in MRD+ patients (73% vs. 22%, P=0.0079). OS, DFS, and PR in MRD+ and MRD-patients were comparable. In our study, the presence of MRD before allo-HSCT (HR=3.858) was an independent factor influencing the probability of relapse. MRD determined by MFC is an independent predictor of the risk of relapse after allo-HSCT in ALL patients. Detection of MRD in patients with ALL in 1st CR before allo-HSCT is necessary to stratify the risk and identify patients who need post-transplant therapy.

GIV is a promising novel poor prognostic factor in liver hepatocellular carcinoma.

Numerous studies have implicated Gα-interacting, vesicle-associated protein (GIV) in the development and metastasis of various cancers. However, its role remains unclear in liver hepatocellular carcinoma (LIHC). We aimed to demonstrate the relationship between GIV and LIHC based on The Cancer Genome Atlas database. We use the Gene Expression Profiling Interactive Analysis and UALCAN to explore the expression of GIV and the survive analysis of GIV in patients with LIHC, genetic alteration analysis, immune infiltration analysis, functional enrichment, protein-protein interaction network analyses, and transcription factor targets of GIV-correlated genes and GIV-interacting genes were performed this study. GIV expression was significantly elevated in LIHC tissues. Remarkable correlation was established between GIV expression and LIHC pathological stage. Low expression of GIV in tumor tissues had a better prognosis than GIV-high expression. GIV alteration frequency was 1.44% in patients with LIHC. GIV-unaltered patients had better survival than GIV-altered ones. Moreover, GIV expression level in LIHC significantly correlated with the infiltration level of immune cells and cancer-associated fibroblasts. The functions of differentially expressed GIVs are associated with the cell cycle pathway. Our data imply that E2F4, E2F1, MYC, and MYCN are key transcription factors for GIV-correlated genes and GIV-interacted genes. GIV may be an adverse prognostic factor for patients with LIHC; it also can be a potential therapeutic target against LIHC. Further studies are required to validate our findings.

LRFN2 binding to NMDAR inhibits the progress of ESCC via regulating the Wnt/β-Catenin and NF-κB signaling pathway.

As a neuronal transmembrane protein, leucine‐rich repeat and fibronectin type‐III domain‐containing protein 2 (LRFN2) can recruit and combine with N‐methyl‐d‐aspartate receptors (NMDARs) to promote nerve growth. Genetic studies suggest that mutations in LRFN2 are associated with various cancers. However, the role and mechanism of LRFN2 in the progression of ESCC have not been elucidated. In this study, we demonstrated that LRFN2 was significantly downregulated in ESCC tissues by qRT‐PCR and immunohistochemistry. Low LRFN2 expression was an adverse prognostic factor in patients with ESCC. Overexpression of LRFN2 effectively suppressed the proliferation, migration, invasion, and epithelial‐to‐mesenchymal transition in vitro and tumor growth in vivo. Bioinformatics analysis indicated that Wnt/β‐catenin signaling regulation was one of the most potential mechanisms and studies confirmed that overexpression of LFRN2 obviously downregulated the expression of β‐catenin, c‐Myc, and cyclin D1 in ESCC cells and tumor tissues. Further studies revealed that LRFN2 plays an anti‐ESCC role by binding with NMDAR‐GRIN2B and this effect can be weakened by NR2B‐selective NMDA antagonist‐NMDA‐IN‐1. Moreover, the bioinformatics analysis showed that the interaction of GRIN2B and GSK3β affects the NF‐κB pathway, which was demonstrated by western blot experiments. Collectively, our results indicate that LRFN2 binding to NMDARs inhibits the progression of ESCC by regulating the Wnt/β‐catenin and NF‐κB pathway, which provides a new therapeutic target for improving the prognosis of patients with ESCC.

Radiomics for differentiating tumor deposits from lymph node metastasis in rectal cancer.

BACKGROUNDTumor deposits (TDs) are not equivalent to lymph node (LN) metastasis (LNM) but have become independent adverse prognostic factors in patients with rectal cancer (RC). Although preoperatively differentiating TDs and LNMs is helpful in designing individualized treatment strategies and achieving improved prognoses, it is a challenging task.AIMTo establish a computed tomography (CT)-based radiomics model for preoperatively differentiating TDs from LNM in patients with RC.METHODSThis study retrospectively enrolled 219 patients with RC [TDs+LNM- (n = 89); LNM+ TDs- (n = 115); TDs+LNM+ (n = 15)] from a single center between September 2016 and September 2021. Single-positive patients (i.e., TDs+LNM- and LNM+TDs-) were classified into the training (n = 163) and validation (n = 41) sets. We extracted numerous features from the enhanced CT (region 1: The main tumor; region 2: The largest peritumoral nodule). After deleting redundant features, three feature selection methods and three machine learning methods were used to select the best-performing classifier as the radiomics model (Rad-score). After validating Rad-score, its performance was further evaluated in the field of diagnosing double-positive patients (i.e., TDs+LNM+) by outlining all peritumoral nodules with diameter (short-axis) > 3 mm.RESULTSRad-score 1 (radiomics signature of the main tumor) had an area under the curve (AUC) of 0.768 on the training dataset and 0.700 on the validation dataset. Rad-score 2 (radiomics signature of the largest peritumoral nodule) had a higher AUC (training set: 0.940; validation set: 0.918) than Rad-score 1. Clinical factors, including age, gender, location of RC, tumor markers, and radiological features of the largest peritumoral nodule, were excluded by logistic regression. Thus, the combined model was comprised of Rad-scores of 1 and 2. Considering that the combined model had similar AUCs with Rad-score 2 (P = 0.134 in the training set and 0.594 in the validation set), Rad-score 2 was used as the final model. For the diagnosis of double-positive patients in the mixed group [TDs+LNM+ (n = 15); single-positive (n = 15)], Rad-score 2 demonstrated moderate performance (sensitivity, 73.3%; specificity, 66.6%; and accuracy, 70.0%).CONCLUSIONRadiomics analysis based on the largest peritumoral nodule can be helpful in preoperatively differentiating between TDs and LNM.

Study of Podoplanin Expression in Head and Neck Squamous Cell Carcinoma.

Background & Objective:Head and Neck Squamous cell carcinoma (HNSCC) is one of the leading cancers worldwide. Cervical lymph node metastasis is the most adverse prognostic factor for patients with HNSCC. As there are no reliable factors in predicting lymph node metastasis, recent researchers focus on identifying various metastasis markers that will aid treatment selection. Podoplanin is a recent marker strongly associated with lymph node metastasis, aggressive tumor behavior, and poor prognosis. The expression of podoplanin in human squamous cell cancers and its association with cancer cell motility suggest a possibility that it could be used as a biomarker to predict lymph node metastasis. To study the expression of podoplanin in head and neck squamous cell carcinoma, determine its association with clinicopathological variables, and predict its use as a biomarker in predicting lymph node metastasis. Methods:The present study was conducted in a tertiary care hospital. Podoplanin expression was studied in 45 cases of HNSCC and its association with clinicopathological variables. The predictive power of podoplanin was further analyzed using univariate and multivariate logistic regression analysis. The positive and negative predictive values of podoplanin were determined concerning the presence or absence of lymph node metastasis.Results:Podoplanin expression is significantly associated with histological grade (P=0.03) and lymph node metastasis (P=0.01). In logistic regression analysis, podoplanin expression (Odds Ratio: 5.66, Confidence Interval: 1.23 -25.87, P=0.02) was a significant independent predictor of lymph node metastasis. Conclusion: Our study demonstrates that podoplanin provides prognostic information and predicts lymph node metastasis which was consistent with our studies in the literature. Thus, podoplanin may help better stratify patients selected for elective neck node dissection in early tumor stages and clinically negative regional disease.

Dynamic plasticity of prostate cancer intermediate cells during androgen receptor-targeted therapy.

Treatment-emergent small cell neuroendocrine prostate cancer (t-SCNC) is associated with an epithelial lineage switch from an androgen receptor (AR)-positive to neuroendocrine (NE)-marker-positive status. Understanding the potential for reversibility of this aggressive disease state has been hampered by the paucity of models suitable for studying rate-limiting, transitional, or intermediate tumor cell subpopulations. We define a dual reporter model that measures acute transcriptional changes in response to castration or AR targeting agents. We identify steady-state transcriptional heterogeneity in AR and NE biomarkers, including intermediate subpopulations that are coordinately high for prostate-specific antigen (PSA) and neuron-specific enoclase (NSE) promoter activity. In the presence of castration or AR inhibitors, intermediate cells were necessary and sufficient for therapy-induced conversion of human PC cells to an NSE-high transcriptional status. Using hormone add-back studies, treatment-induced PSA-NSE transcriptional plasticity was reversible in PTEN-deficient PC cells but not in the presence of secondary genetic driver genes, including MYCN.

Prognostic Value of Metabolic Syndrome in Patients With Non-ST Elevated Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

ObjectiveWe aim to investigate the prognostic effects of metabolic syndrome (MS) on patients with non-ST elevated myocardial infarction (NSTEMI) after percutaneous coronary intervention (PCI).MethodsPatients with NSTEMI undergoing PCI were consecutively collected. According to the presence or absence of MS, they were divided into two groups and followed up for 1 year. The endpoint was major adverse cardiovascular events (MACE), including all-cause death, unstable angina hospitalization, heart failure (HF) hospitalization, non-fatal recurrent myocardial infarction (MI), and target lesion revascularization. Also, six subgroups were made according to gender, age, left ventricular ejection fraction (LVEF), Global Registry of Acute Coronary Events (GRACE) score, hypersensitive troponin (hsTNT), and several diseased vessels. Cox proportional hazard model was adopted to analyze the effect of MS on MACE in all the patients and different subgroups.ResultsA total of 1,295 patients were included in the current analysis and 660 (50.97%) of them had MS. About 88 patients were lost to follow-up, and the overall average follow-up was 315 days. MS was an independent risk factor for MACE (HR 1.714, CI 1.265–2.322, p = 0.001), all-cause death, heart failure (HF) hospitalization, and non-fatal recurrent MI. In the MS component, BMI ≥28 kg/m2 was positively associated with MACE. Subgroup analysis indicated the prognostic value of MS was more striking for patients with the following: age of >60, LVEF of ≤40%, GRACE of >140, multivessel disease, or hsTNT of >0.1 ng/ml.ConclusionsThe MS was a robust adverse prognostic factor in patients diagnosed with NSTEMI, especially among those of older age and at higher ischemic risk. A BMI of ≥28 kg/m2 independently predicted the occurrence of MACE. Prognosis may be improved by controlling abdominal obesity.