Multivariate Survival Analysis Research Articles

Low Expression of FAM96B is Associated with Poor Prognosis in Hepatocellular Carcinoma.

Recently, studies on FAM96B functions mainly focused on its role in maintaining the normal physiological function of cells. However, the clinical implications of FAM96B in hepatocellular carcinoma (HCC) are still unclear. FAM96B mRNA expression was detected in human HCC tissues and the matched nontumorous tissues by quantitative real-time reverse transcription (qRT-PCR) and then validated in The Cancer Genome Atlas (TCGA) database. Immunohistochemistry assay (IHC) was performed on all 137 cases of HCC samples to examine the protein level of FAM96B. Subsequently, the associations between FAM96B expression and clinicopathological parameters and prognosis were further analyzed. The mRNA level of FAM96B was found to be significantly lower in HCC tissues compared to non-tumorous tissues, as observed in both the local hospital and TCGA database.Immunohistochemistry assay analysis revealed a decrease in FAM96B expression in 78 out of 137 cases, which was significantly associated with larger tumor size, higher Barcelona clinic liver cancer or Child stage, and early distant metastasis. Patients with low FAM96B levels tended to have an unfavorable disease-free and overall survival. Moreover, FAM96B was identified as an independent predictor of patient prognosis in both univariate and multivariate survival analyses. Mechanistically, FAM96B was found to inhibit cancer progression by inducing apoptosis in liver cancer cells and inhibiting their growth. Our findings provide the first evidence suggesting the involvement of FAM96B in the progression of HCC. Additionally, FAM96B could potentially serve as a marker for tumor recurrence and prognosis in HCC patients.

Long-term Outcomes of Persistent Postoperative Opioid Use: A Retrospective Cohort Study.

To determine the association between PPOU and the long-term risk of OUD and opioid overdose. PPOU is a commonly used outcome in the surgical literature; its incidence and risk factors have been well described. However, its association to long term outcomes, including OUD and opioid overdose, is unknown. A retrospective cohort study utilizing the Veterans Health Administration corporate data warehouse. Patients undergoing any surgery between January 1, 2008 and December 31, 2018 were included and followed until December 31, 2020. Univariate and multivariate survival analysis were used to determine the association between PPOU and OUD and overdose. Sensitivity analyses were conducted to determine the impact of different definitions of persistent opioid use and the effect of preoperative opioid use. A total of 344,745 patients undergoing surgery were included and followed for a median of 6.18 years (IQR 3.53-9.12). PPOU was associated with an increased hazard of developing both OUD (HR = 1.88, CI: 1.81-1.95, P < 0.001) and overdose (HR = 1.83, CI: 1.72-1.94, P < 0.001). This association remained consistent after adjustment for comorbidities and across all sensitivity analyses. Surgical patients who develop PPOU are at increased risk of both OUD and overdose as compared to surgical patients who do not develop persistent use.

Hierarchically Positioning Laparoscopic Microwave Ablation in the Therapeutic Span of Early Hepatocellular Carcinoma: A Real-Life Comparative Analysis.

Laparoscopic microwave ablation (LMWA) has yet to gain a specific place in treatment guidelines for early hepatocellular carcinoma (HCC). This study compared the outcomes of LMWA and trans-arterial chemoembolization (TACE) for early non-resectable patients with HCC, taking percutaneous radiofrequency ablation (PRFA) as the reference treatment. A retrospective multicenter observational study was conducted, enrolling non-transplantable, non-resectable patients who had early HCC treated with LMWA (n = 658) from Padua and Milan centers, and with PRFA (n = 844), and TACE (n = 425) from the ITA.LI.CA multicenter database. The matching-adjusted indirect comparison (MAIC) method was used to obtain weighted LMWA and TACE populations similar to the reference PRFA population. Laparoscopic ablation showed an excellent safety profile, and MAIC-weighted early postoperative deaths were comparable among the groups. The MAIC-weighted overall survival was similar between the LMWA (1-, 3-, and 5year survival of 91.0 %, 67.9 %, 47.0 %, respectively) and PRFA (1-, 3- and 5year survivals of 90.0 %, 64.7 %, 46.6 %, respectively) groups (p = 0.678) and significantly better for the LMWA group than for the TACE group (1-, 3- and 5year survivals of 84.7 %, 48.8 %, 33.6 %, respectively) (p < 0.001). Weighted multivariate overall survival analysis and competing risk/subgroup analyses confirmed the non-inferiority of LMWA to PRFA and its superiority to TACE. The LMWA- and PRFA-treated patients had a significantly lower risk of HCC-related death (p = 0.004) than the TACE-treated patients (p = 0.001). Conversely, the groups did not differ significantly in terms of non-HCC-related deaths. The non-inferiority of LMWA to PRFA, its superiority to TACE, and its applicability to a wide range of presentations with few contraindications support its inclusion among radical therapies for treating early-HCC patients.

Prognostic Nutritional Index is a valuable preoperative prognostic biomarker in Mexican patients surgically intervened on gastrointestinal stromal tumors: a retrospective cohort study.

The immunonutritional status of cancer patients has a profound impact on lifespan. Prognostic Nutritional Index (PNI) evaluates prognosis in operated patients with both neoplastic and non-neoplastic conditions. This study estimates the overall survival (OS) of Mexican patients operated on gastrointestinal stromal tumors (GIST) based on PNI. Immune-nutritional status was retrospectively analyzed in a cohort of 104 patients operated on GIST. Receiver operating characteristic (ROC) curves and X-tile software were used to estimate the optimal cutoff point and predict OS stratifying patients by PNI. Survival curves were obtained through Kaplan-Meier and log-rank methods. Multivariate analysis of survival was performed by Cox regression. PNI (≥ 36.5) (p = 0.024) and mitotic index (≥ 5) (p = 0.013) were the only independent prognostic scores; the PNI-high group had better survival with 81.5% less risk of death (HR = 0.185). High PNI was correlated with favorable characteristics, i.e., low/intermediate risk (p = 0.046), reduced mitotic index (< 5) (p = 0.001), and younger age (< 55years, p = 0.047). PNI ≥ 36.5 entails a better prognosis for Mexican patients with surgically resected GIST. PNI represents a simple, reliable, and cost-effective prognostic tool, besides the pathological approach.

The impact of lymph node involvement on adjuvant chemotherapy and survival in patients with resected invasive intraductal papillary mucinous neoplasm: a propensity score matching study based on SEER database and external validation

Background: Limited knowledge and guidelines exist for invasive intraductal papillary mucinous neoplasm (IPMN). This study aims to explore the significance of lymph node involvement on adjuvant chemotherapy (ACT) for invasive IPMN. Materials and Methods: Patients diagnosed with invasive IPMN were selected from both the SEER database and our hospital. Kaplan-Meier analysis, Cox proportional hazards model, and propensity score matching (PSM) were employed in this study. Results: In the SEER group, multivariate analysis involving 775 patients revealed that several factors including age, tumor differentiation, AJCC-T staging, N staging, and TNM stage significantly influenced overall survival (OS) and cancer-specific survival (CSS). Turning to the Zhongshan Hospital group (ZS group), which had 94 recruited patients, multivariate analysis for OS, CSS, and recurrence-free survival (RFS) showed that AJCC N staging emerged as the most significant risk factor, with HR values of 4.664, 4.955, and 3.175, respectively. In subgroup analysis, ACT provided survival advantages for patients with positive lymph node metastasis (LNM). In a PSM analysis focused on patients with positive LNM, the comparison revealed that ACT emerged as a critical factor influencing both OS and CSS (both p&lt;0.005). Especially, these patients younger than 60 year old, or those with AJCC-T2-N+ staging were found to get apparently benefit from ACT as revealed by our subgroup interaction analysis. Conclusion: LNM plays a pivotal role in the management of invasive IPMN patients underwent surgery, and ACT might be a beneficial therapeutic option for individuals concurrent with LNM, particularly among those younger than 60 year old, or with AJCC-T2-N+ staging.

Using Electrocardiogram to Assess Diastolic Function and Prognosis in Mitral Regurgitation

BackgroundThe determination of left ventricular diastolic function (LVDF) in patients with significant (≥moderate) mitral regurgitation (MR) poses a complex challenge. We recently validated an artificial intelligence–enabled electrocardiogram (AI-ECG) algorithm to estimate LVDF. ObjectivesThis study sought to evaluate the risk of all-cause mortality across AI-ECG LVDF-derived myocardial disease (MD) grades in MR. MethodsThis was a retrospective study including all patients in the AI-ECG LVDF study testing group who underwent comprehensive transthoracic echocardiography confirming significant MR and electrocardiogram within 14 days of each other at the Mayo Clinic between September 2001 and April 2023. AI-ECG LVDF status was determined based on the index electrocardiogram and used to categorize patients into 3 stages of MD: MD-1, normal or grade 1 LVDF; MD-2, grade 2 LVDF; and MD-3, grade 3 LVDF. ResultsOf 4,019 patients with significant MR (mean age 69.8 years; 49.0% women), 1,175 (29.2%), 1,881 (46.8%), and 963 (24.0%) were classified by AI-ECG as MD-1, MD-2, and MD-3, respectively. The median mitral effective regurgitant orifice area was 26 mm2 (Q1-Q3: 20-36 mm2). Over a median follow-up of 3.5 years, 1,636 (40.7%) patients died. In multivariable survival analysis adjusted for multiple risk factors, a higher diastolic function grade was independently associated with an increased death risk (MD-2, adjusted HR [aHR]: 1.99; 95% CI: 1.62-2.45; MD-3, aHR: 2.65; 95% CI: 2.11-3.34). These findings were consistent when accounting for mitral valve intervention and across various sensitivity and subgroup analyses. ConclusionsIn patients with significant MR, the grading of LVDF by AI-ECG is independently associated with all-cause mortality.

The role of autophagy dysregulation in low and high-grade nonmuscle invasive bladder cancer: A survival analysis and clinicopathological association

IntroductionBladder cancer disproportionately affects men and often presents as nonmuscle-invasive bladder cancer (NMIBC). Despite initial treatments, the recurrence and progression of NMIBC are linked to autophagy. This study investigates the expression of autophagy genes (mTOR, ULK1, Beclin1, and LC3) in low and high-grade NMIBC, providing insights into potential prognostic markers and therapeutic targets. Material and methodsA total of 115 tissue samples (n = 85 NMIBC (pTa, pT1, and CIS) and n = 30 control from BPH patients) were collected. The expression level of autophagy genes (mTOR, ULK1, Beclin1, and LC3) and their proteins were assessed in low and high-grade NMIBC, along with control tissue samples using quantitative real-time polymerase chain reaction and western blotting. Association with clinicopathological characteristics and autophagy gene expression was analyzed by multivariate and univariate survival analysis using SPSS. ResultIn high-grade NMIBC, ULK1, P = 0.0150, Beclin1, P = 0.0041, and LC3, P = 0.0014, were substantially downregulated, whereas mTOR, P = 0.0006, was significantly upregulated. The KM plots show significant survival outcomes with autophagy genes. The clinicopathological characters, high grade (P = 0.019), tumor stage (CIS P = 0.039, pT1 P = 0.018, P = 0.045), male (P = 0.010), lymphovascular invasion (P = 0.028) and autophagy genes (ULK1 P = 0.002, beclin1 (P = 0.010, P = 0.022) were associated as risk factors for survival outcome in NMIBC patients. ConclusionThe upregulated mTOR, downregulated ULK1, and beclin1 expression is linked to a high-grade, CIS and pT1 stage, resulting in poor recurrence-free survival and progression-free survival and highlights the prognostic significance of autophagy gene in nonmuscle-invasive bladder cancer.

Association Between Socioeconomic Factors and Childhood Acute Lymphoblastic Leukemia Treatment- and Survival-Related Outcomes in Canada.

Studies examing the impact of socioeconomic factors on outcomes in childhood acute lymphoblastic leukemia (ALL) have yielded inconsistent findings. We aimed to determine whether socioeconomic status (SES) or healthcare access are associated with the presence of potentially time-sensitive high-risk features at diagnosis, times to diagnosis or treatment, or survival among children with ALL in Canada. We conducted a retrospective cohort study of all children aged less than 15years diagnosed with first primary ALL between 2001 and 2019 using the Cancer in Young People in Canada national Data Tool, which is population-based. SES was measured using neighborhood income quintiles, and healthcare access proxy measured as distance to treating center. We used logistic regression to examine the associations between income quintile and distance and two potentially time-sensitive indicators of high-risk ALL at diagnosis, white blood cell count (WBC) ≥50×109/L, and central nervous system (CNS) disease. We used Cox proportional hazards to examine associations with time-to-event outcomes (times to diagnosis and treatment, event-free survival [EFS], and overall survival [OS]). We included 4189 patients. In multivariable analyses, no associations were found between income quintile and potentially time-sensitive high-risk features at diagnosis, time to diagnosis or treatment, or OS. The only significant SES measure in multivariable survival analysis was superior EFS among those in income quintile 4 as compared to those in the lowest income quintile with a hazard ratio (HR) of 0.70 (confidence interval [CI]: 0.54-0.91). Living at increased distance from treating center was not associated with high WBC at diagnosis, time to diagnosis, EFS, or OS. Associations were seen between distance to treating center and CNS disease at diagnosis and time to treatment, but without a clear pattern across distance quartiles. Children diagnosed with ALL and treated within Canada's universal healthcare system experience similar treatment and survival outcomes regardless of SES and distance to treatment center. Further work is required using individual-level SES and demographic data to determine if any associations exist, and qualitative assessments to understand barriers to care.

Lymph node density as prognostic factor in regional recurrent or residual head and neck cancer

Background Prognostic factors from neck dissection for regional recurrent or residual head and neck cancer remain undetermined. Aims/objectives We studied whether continuous variables from pathologic lymph nodes of salvage neck dissection could estimate survival outcomes in patients with head and neck squamous cell carcinomas (HNSCC). Materials and methods Pathologic continuous variables from neck dissection without primary tumor resection in 184 patients with HNSCC were retrospectively evaluated. Cutoff values from both lymph node density (LND) and log odds of positive lymph nodes (LODDS) as the variables were applied to death estimation. Uni-/multivariate survival analyses adjusting for pathologic N classification and extranodal extension were evaluated by log-rank test or Cox’s proportional hazard model, respectively. Results LND ≥ 0.14 and LODDS ≥ −1.72 were significantly related to univariate shorter survival outcomes. Multivariate analysis indicated a significant association between LND ≥ 0.14 and shorter overall (hazard ratio [HR] = 2.16, 95% confidence interval [CI] = 1.30–3.58), local recurrence-free (HR = 2.34, 95% CI = 1.06–5.16), regional recurrence-free (HR = 2.32, 95% CI = 1.27–4.25), and distant metastasis-free survival (HR = 2.17, 95% CI = 1.31–3.61). Conclusions and significance Based on the obtained results, increased LND was a poor prognostic factor following salvage neck dissection.

Predictors of poor treatment outcomes among drug-resistant tuberculosis patients in Hunan province, China

BackgroundDrug-resistant tuberculosis (DR-TB) is a significant public health concern, often resulting in poor treatment outcomes. This study aims to identify predictors of poor treatment outcomes among patients with DR-TB in Hunan Province, China. MethodsA retrospective cohort study was conducted in Hunan Province using data collected between 2013 and 2018 among patients with DR-TB treatment. Univariable and multivariable parametric survival analyses were performed using a shared frailty survival model with a Weibull distribution and Gamma frailty to identify determinants of poor treatment outcomes. Adjusted hazard ratios (AHR) with a 95 % confidence interval (CI) were calculated for the best-fitted model. The goodness of fit for the model was assessed using the Cox-Snell residual test. ResultsA total of 1384 bacteriologically confirmed DR-TB patients were included in the analysis. Of these, 9.97 % (95 % CI: 8.05–11.67 %) experienced poor treatment outcomes. The hazard of poor treatment outcomes was significantly higher among patients with a history of previous TB treatment compared to those with new TB (AHR = 1.82, 95 % CI: 1.27–2.61). Additionally, each one-day delay in diagnosis was associated with a slightly increased hazard of poor treatment outcomes (AHR = 1.00034, 95 % CI:1.000041–1.00064). Patients who received medication supervision and consistent treatment follow-up (i.e., systematic management) had a significantly lower hazard of poor treatment outcomes than those without systematic management (AHR = 0.08, 95 % CI: 0.05–0.14). ConclusionA substantial proportion of DR-TB patients in Hunan Province experience poor treatment outcomes, with prior TB treatment and delays in diagnosis being key predictors. Early diagnosis and systematic management, including medication supervision and consistent follow-up, significantly reduce the risk of poor treatment outcomes. Focused interventions for previously treated TB cases are crucial to improving treatment outcomes and mitigating the risk of long-term physical sequelae among DR-TB survivors.

Impact of longitudinal changes in serum uric acid levels and weight gain on new-onset atrial fibrillation—The Nishimura Health Survey: a retrospective cohort study

ObjectiveUric acid (UA) and obesity are significant risk factors for new-onset atrial fibrillation (AF). Based on the pathogenesis mechanisms of new-onset AF involving obesity and UA, it is possible that...

Prognostic factors for patients with cancer-associated dermatomyositis: a retrospective, multicenter cohort study of 73 patients.

To investigate factors associated with dermatomyositis (DM) complete clinical response and overall survival with a focus on the use of immunosuppressive therapies in patients with cancer-associated DM. We performed a multicentre, retrospective cohort study. Multivariable survival analyses used a Cox model with time-dependent covariates and adjustments with inverse probability censoring weighting. We included 73 patients with cancer-associated DM. Median follow-up was 3.92 years. Overall, 40 (54.8%) patients achieved cancer remission, with DM complete clinical response in 28/40 (70.0%). DM complete clinical response was associated with cancer remission (hazard ratio [HR] 2.46, 95%CI [1.13-5.32]) and younger age (HR 0.68, 95%CI [0.49-0.95]). Risk of mortality was associated with sustained cancer activity (HR 12.93, 95% CI [2.42-69.25]), male sex (HR 2.82, 95% CI [1.19-6.70]), and older age (HR 1.86, 95% CI [1.26-2.79]) but not sustained DM activity (HR 0.40, 95%CI [0.13-1.26]). Oral corticosteroids use was a protective factor only on univariate analysis (HR 0.18, 95% CI [0.08-0.42]). This study provides strong evidence of a significant association between the evolutions of DM and cancer, both in terms of overall survival and DM complete clinical response. Immunosuppressive treatments for DM were not significantly associated with mortality. ClinicalTrials.gov, NCT04637672.

Predictive value of direct bilirubin and total bile acid in lung adenocarcinoma patients treated with EGFR-TKIs

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have been the standard treatment for patients with sensitizing EGFR mutation. However, almost all patients eventually acquire resistance to EGFR-TKIs. Therefore, easily available parameters to estimate the outcome of lung adenocarcinoma patients treated with EGFR-TKIs are in urgent need. Lung adenocarcinoma patients harbored EGFR sensitive mutant and received EGFR-TKIs as first-line or second-line treatment were recruited in the study. X-tile software were utilized to determine the optimal cut-off value of Alkaline phosphatase (ALP), direct bilirubin (DB), total bile acid (TBA), and high-density lipoprotein-cholesterol (HDL-C). The prognostic value of ALP, DB, TBA, and HDL-C for Progression-free survival (PFS) in patients were evaluated by the Kaplan-Meier curve. We applied univariate and multivariate survival analysis to identify the independent predictor for PFS in patients with EGFR-mutant advanced lung adenocarcinoma and received EGFR-TKIs. A total of 131 lung adenocarcinoma patients with a median age of 58 years old were included in the final analysis. Patients with elevated level of DB and HDL-C showed a longer PFS, while high level of ALP and TBA indicated shorter PFS in response to EGFR-TKI treatment. The multivariate survival analyses revealed a significant association of prolonged PFS with increased DB, and decreased TBA. In conclusion, these findings suggest that DB and TBA were significant independent predictors of PFS in EGFR-TKI-treated patients with advanced lung adenocarcinoma.

Dynamic contrast-enhanced and diffusion-weighted MR imaging for predicting tumor growth of sporadic vestibular schwannomas: a prospective study.

Advanced MR imaging, such as diffusion-weighted (DWI) and dynamic contrast-enhanced (DCE) imaging, may provide valuable non-invasive information on intrinsic tumor biology. This study aims to evaluate apparent diffusion coefficient (ADC) and DCE-MRI-derived microvascular parameter values (Ktrans, ve, and vp) as potential imaging predictors for future sporadic vestibular schwannoma (VS) growth. In this prospective cohort study, patients with newly diagnosed unilateral sporadic VS and an initial wait-and-scan strategy were enrolled between January 2021 and January 2023. Patients underwent a single timepoint comprehensive MRI protocol, including DWI and DCE-MRI sequences. The estimated values of ADC, Ktrans, ve, and vp were calculated using established pipelines on a voxelwise basis within the delineated tumor region of interest. Associations of the estimated parameter values with volumetric growth were evaluated in uni- and multivariable logistic regression and survival analyses. Of the 110 analyzed patients, 70 (64%) exhibited growth during follow-up. A significant correlation was primarily observed between the DCE-MRI-derived parameters and VS growth. The combination of mean Ktrans (P<0.001) and ve (P<0.001) tumor values provided an internally validated model with an AUC of 0.85 for growth, yielding a sensitivity of 89% and specificity of 73% at the optimized cutoff value. Only the mean ADC values were found to be significantly higher in shrinking tumors (P=0.04). The strongly significant correlation observed between VS growth and Ktrans and ve tumor values indicates great potential of the non-invasive DCE-MRI for individualized VS management in clinical practice. External validation is needed to further substantiate these findings.

Multimodality Therapy and Survival Outcomes in Resectable Primary Small Cell Carcinoma of the Esophagus: A Multicenter Retrospective Study.

Currently, optimal treatment strategy for resectable primary small cell carcinoma of the esophagus (PSmCCE) remains controversial. To address this, we conducted a multicenter study to evaluate treatment patterns and long-term survival of PSmCCE patients who underwent radical resection. This retrospective multicenter study included resected PSmCCE patients who received radical resection at seven high-volume cancer centers. Overall survival (OS) and median survival time (MST) were calculated by using a Kaplan-Meier method and the log-rank test was utilized to assess differences. Multivariable Cox analysis was performed to identify independent prognostic factors. A total of 352 patients with resected PSmCCE were included. For PSmCCE with stage cT1-2N0M0, patients who received surgery plus adjuvant therapy showed better survival than those who received surgery alone (5-year OS rate: 32.8% vs. 19.2%, MST: 44.0 vs. 33.0 months, P = 0.035). Multivariable Cox survival analysis revealed an independent correlation between receiving surgery plus adjuvant therapy and improved OS (hazard ratio [HR] 0.529; 95% confidence interval [CI] 0.280-0.997; P = 0.049). For stage cT3N0M0/T1-3N1M0 PSmCCE, patients who received neoadjuvant therapy followed by surgery had superior long-term survival compared with those who received surgery combined with adjuvant therapy and those who received surgery alone (5-year OS rate: 27.2% vs. 9.5% vs. 0%, MST: 36.0 vs. 24.0 vs. 20.0 months, P = 0.014). Multivariable Cox survival analysis showed that neoadjuvant therapy was independently associated with improved OS (HR 0.384, 95% CI 0.203-0.728; HR 0.550, 95% CI 0.312-0.968; P = 0.013). Adjuvant therapy was associated with improved survival in stage cT1-2N0M0 PSmCCE, but this should be confirmed in prospective studies. For stage cT3N0M0/T1-3N1M0 cases, neoadjuvant therapy followed by surgery should be considered.

Frailty as an independent predictor for midterm adverse outcomes in the elderly undergoing primary percutaneous coronary intervention: A longitudinal cohort study.

Frailty is associated with poor health outcomes in elderly population. However, its effect on midterm outcomes in elderly patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) remains unknown. This study aimed to evaluate the association between frailty, as classified by the Clinical Frailty Scale (CFS), and midterm adverse outcomes in elderly STEMI patients after primary PCI. In this prospective, observational, multicenter cohort study, frailty status of 426 STEMI patients aged ≥60 years undergoing primary PCI was determined using the nine-point CFS 2 weeks before the occurrence of STEMI. Patients scoring at least four points on the CFS were considered frail. The primary outcome was a composite of cardiovascular death or readmission. Secondary outcomes included cardiovascular death, cardiovascular readmission, heart failure-related death or readmission, and myocardial reinfarction. Follow-up data were collected through medical record reviews and/or telephone interviews. Of 426 elderly patients, 116 were frail. The median follow-up period was 15 months (interquartile range 5-19 months). Primary outcome events occurred in 87 (75.0%) frail and 75 (24.2%) nonfrail patients. The adjusted hazard ratio was 3.278 after model selection using the Bayesian Model Averaging approach (95% confidence interval 2.372-4.531). Multivariate Cox proportional hazard survival analysis showed that frailty was significantly associated with a higher prevalence of all secondary outcome events after adjusting for TIMI, PAMI, and CADILLAC risk scores. Frailty, as defined by the CFS, was independently associated with midterm adverse outcomes in elderly patients undergoing primary PCI for STEMI.

Circulating Micro-RNAs Predict the Risk of Recurrence in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a high tendency for developing a recurrent disease. Circulating micro-RNAs (cmiRNAs) obtained through liquid biopsy are potential prognostic biomarkers for the assessment of TNBC recurrence risk. In this study, we sequenced cmiRNAs from the serum samples of 14 recurrent and 19 non-recurrent TNBC cases and compared expression profiles in relation to recurrence status, survival data and miRNA expression in matched tumor samples. Differential expression analysis between recurrent and non-recurrent cases identified ten differentially expressed (DE) cmiRNAs, of which cmiRNAs miR-21-5p (p = 0.030, HR = 1.87, 95% CI 1.06-3.30), miR-16-5p (p = 0.032, HR = 0.53, 95% CI 0.30-0.95), and miR-26b-5p (p = 0.023, HR = 0.52, 95% CI 0.29-0.91) were associated with recurrence-free survival in multivariable survival analysis. Expression profiles of matched tumor and serum samples were shown to correlate with each other. DE cmiRNAs were associated with common cancer-related signaling pathways and improved the overall predictive performance of the logistic regression model assessing the recurrence risk. Our results indicate that recurrent and non-recurrent TNBC differ in their cmiRNA expression profiles, and that three specific cmiRNAs can be used to assess the risk of recurrence in TNBC.

Survival outcomes for HER2-low breast cancer: Danish national data.

We investigated the prognosis of breast cancer (BC) with low expression of human epidermal growth factor receptor 2 (HER2), as previous studies have found varying impacts on survival of HER2-low BC compared with HER2 0 BC (HER2 IHC score of 0). HER2-low is defined as a score of 1+ or 2+ in an immunohistochemical (IHC) assay without HER2 gene amplification. Patients with HER2 0 or HER2-low BC from the national Danish Breast Cancer Group database were examined by multivariable survival analysis in a retrospective noninterventional investigation. Patients were grouped as either HER2 0 or HER2-low. The primary endpoint was time to recurrence (TR), and the secondary endpoints were overall survival (OS) and distant recurrence-free interval (DRFI). 41,610 patients were included (12,981 with HER2 0 BC and 28,629 with HER2-low BC). HER2-low BC was associated with a lower risk of recurrence (hazard ratio [HR]: 0.92, p = 0.03). Regarding secondary endpoints, HER2-low disease was linked to improved overall OS (HR: 0.94, p = 0.02). No statistically significant effect of HER2-low was found for DRFI, along with no differential effect of HER2-low according to estrogen receptor (ER) status. HER2-low BC was found to show an improved HR for OS and DRFI compared with HER2 0 BC; however, further studies are need to establish whether it represents a separate biological entity.

Abstract 4136202: Incident Hypertension and Survival Outcomes After Immune Checkpoint Inhibitor Initiation

Introduction: Immune checkpoint inhibitors (ICIs) are commonly used as anticancer agents linked with dramatic antitumor response but are associated with cardiotoxicity. Recent isolated reports have suggested ICIs may link with hypertension (HTN) after years of treatment. Yet, the timing and long-term ramifications of this HTN are unknown. Methods: From a large cohort of well-phenotyped cancer patients treated with ICIs from 2011-2022, we assessed the incidence of new or worsened HTN [systolic blood pressure (SBP) ≥130 mmHg (or in a higher HTN stage) on two occasions within a three-month period or addition of an antihypertensive medication] after ICI initiation. Secondary endpoints included major cardiovascular events (MACE), defined as symptomatic arrhythmia, myocardial infarction, stroke, heart failure, or cardiac death. Observed incident HTN rates were compared to Framingham-predicted rates, using JNC 8 cutoffs of 140/90 mmHg. Landmark analysis, excluding patients who were observed to have new HTN but had SBPs ≥130 mmHg on two occasions within six-months prior to ICI initiation, identified patients with possible undiagnosed HTN. Multivariable regression and survival analysis were used to define factors associated with new worsened HTN and MACE and the relationship between SBP increase and MACE risk. Further, the effect of standard antihypertensive classes on the prevention of ICI-related HTN will be assessed. Results: Overall, from 312 patients treated with ICIs (mean age 63.5 years, 67.4% baseline HTN, 11.0% on dual ICI-therapy), 50.0% (156/312) developed new or worsened HTN over a mean of 27 months follow-up. Cumulative incidence of new HTN by 1-year was 50.0% wherein the mean peak increase in SBP was 12 mmHg. In landmark analysis, excluding those with undiagnosed HTN and applying the JNC 8 cutoff of ≥140/90 mmHg, the observed new HTN rate was 21.4% at 1 year, &gt;2-fold higher than the Framingham-predicted rate of 9.3% (RR 2.3, P &lt;0.0001). In those with preexisting HTN, 49% developed worsened HTN. In multivariate analysis, only time on ICI treatment, ECOG status, and autoimmune disease history were associated with new or worsened HTN after ICI-initiation ( P &lt;0.05 for all). Further, only prior autoimmune disease and ECOG status associated with MACE; while beyond traditional cancer factors, only new or worsening HTN associated with lower mortality. Conclusions: Collectively, these data suggest that HTN may be common with ICIs, and prognosticates survival.

BIOS-03. CLINICAL PRESENTATION, MANAGEMENT, AND OUTCOME IN NEUROLYMPHOMATOSIS: A SYSTEMATIC REVIEW AND ANALYSIS OF INDIVIDUAL PATIENT DATA FROM 459 CASES

Abstract BACKGROUND Neurolymphomatosis (NL) refers to lymphomatous infiltration of the peripheral nervous system (PNS). NL diagnosis and treatment are challenging given the broad differential diagnosis of peripheral neuropathy, the lack of larger cohorts and the subsequent unavailability of prognostic factors or consensus therapy. This study aimed to define characteristics and prognostic factors of NL. METHODS A systematic review of the literature (2004-2023) was performed using PubMed and Scopus databases and reported following PRISMA guidelines. Clinical, radiological, pathological and outcome information were extracted. Multivariable survival analyses were performed using Cox proportional hazard models. RESULTS A total of 459 NL cases from 264 studies were accumulated. NL was the first manifestation of malignancy (primary NL) in 197 patients. PNS relapse of known non-Hodgkin lymphoma (secondary NL) occurred in 262 cases after a median 12 months. NL predominantly presented with rapidly deteriorating, asymmetric painful polyneuropathy. Infiltrated structures included peripheral nerves (56%), nerve roots (52%), plexus (33%) and cranial nerves (32%). Diagnosis was established at a median of 3 months after symptom onset with substantial delays in primary NL. It mainly relied on PNS biopsy or FDG-PET, which carried high diagnostic yields (&amp;gt; 90%). Post mortem diagnoses were rare (3%). Most cases were classified as B-cell (90%) lymphomas. Tumor-directed therapy was administered in 96% of patients and typically consisted of methotrexate or rituximab-based polychemotherapy. Median overall survival was 18 months. Primary NL without concurrent systemic disease outside the nervous system (hazard ratio [HR]: 0.44; 95% confidence interval (CI): 0.25-0.78; p = 0.005), performance status (ECOG &amp;lt; 2, HR: 0.30; 95% CI: 0.18-0.52; p &amp;lt; 0.0001), and rituximab-based treatment (HR: 0.46; 95% CI: 0.28-0.73; p = 0.001) were identified as favorable prognostic markers on multivariable analysis when adjusting for clinical and sociodemographic parameters. CONCLUSIONS Advances in neuroimaging modalities, particularly FDG-PET, facilitate NL diagnosis and offer a high diagnostic yield. Rituximab-based therapy improves NL outcome. Findings may assist clinicians in early recognition, prognostic stratification, and treatment of NL.