Log-rank Test Research Articles

Unveiling the impact of cirrhotic cardiomyopathy on portal hemodynamics and survival after transjugular intrahepatic portosystemic shunt: a prospective study.

The placement of Transjugular intrahepatic portosystemic shunt (TIPS) results in a sudden increase in central circulating blood volume, which requires proper regulation of the cardiovascular system. We aimed to investigate the impact of TIPS on cirrhotic cardiomyopathy (CCM). A consecutive case series of patients with cirrhosis who underwent TIPS were evaluated by echocardiography and pressure measurements before, immediately after TIPS and 2-4 days later (delayed). Furthermore, all patients underwent a one-year follow-up. In this study, 107 patients were enrolled, 38 (35.5%) with CCM. Echocardiography revealed an increase in postoperative left ventricular filling pressure accompanied by an elevation in left ventricular ejection fraction (LVEF). However, patients in the CCM group exhibited lower LVEF and mean arterial pressure (MAP) compared to the non-CCM group. Post-TIPS, CCM patients showed increased right atrium pressure (RAP) that normalized within 2-4 days, whereas non-CCM patients had lower RAP than baseline. Compared to patient without CCM, CCM patients revealed lower immediate (16.7 ± 4.4 vs. 18.9 ± 4.8, p = 0.022) and delayed 15.9 ± 3.7 vs. 17.7 ± 5.3, p = 0.044) portal vein pressures (PVP) and portal pressure gradients (PPG) (7.7 ± 3.4 vs. 9.2 ± 3.6, p = 0.032 and 10.1 ± 3.1 vs. 12.3 ± 4.9, p = 0.013). The 1-year mortality rates were 13.2% for CCM patients and 4.3% for non-CCM patients (log-rank test, p = 0.093), with MELD score, and preoperative RAP significantly associated with the mortality. Cirrhotic patients with CCM exhibit lower PVP and PPG immediately after TIPS and 2-4 days later, without significantly impacting one-year survival outcomes.

Prognostic clinical and biological markers for amyotrophic lateral sclerosis disease progression: validation and implications for clinical trial design and analysis

With increasing recognition of the value of incorporating prognostic markers into amyotrophic lateral sclerosis (ALS) trial design and analysis plans, there is a pressing need to understand which among the prevailing clinical and biochemical markers have real value, and how they can be optimally used. A subset of patients with ALS recruited through the multi-center Phenotype-Genotype-Biomarker study (clinicaltrials.gov: NCT02327845) was identified as "trial-like" based on meeting common trial eligibility criteria. Clinical phenotyping was performed by evaluators trained in relevant assessments. Serum neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH), urinary p75ECD, plasma microRNA-181, and an array of biochemical and clinical measures were evaluated for their prognostic value. Associations with functional progression were estimated by random-slopes mixed models of ALS functional rating scale-revised (ALSFRS-R) score. Associations with survival were estimated by log-rank test and Cox proportional hazards regression. Potential sample size savings from adjusting for given biomarkers in a hypothetical trial were estimated. Baseline serum NfL is a powerful prognostic biomarker, predicting survival and ALSFRS-R rate of decline. Serum NfL <40pg/mL and >100pg/mL correspond to future ALSFRS-R slopes of ∼0.5 and ∼1.5 points/month, respectively. Serum NfL also adds value to the best available clinical predictors, encapsulated by the European Network to Cure ALS (ENCALS) predictor score. In models of functional decline, the addition of NfL yields ∼25% sample size saving above those achieved by inclusion of either clinical predictors or ENCALS score alone. The prognostic value of serum pNfH, urinary p75ECD, and plasma miR-181ab is more limited. Among the multitude of biomarkers considered, only blood NfL adds value to the ENCALS prediction model and should be incorporated into analysis plans for all ongoing and future ALS trials. Defined thresholds of NfL might also be used in trial design, for enrichment or stratified randomisation, to improve trial efficiency. NIH (U01-NS107027, U54-NS092091). ALSA (16-TACL-242).

Prognostic value of computed tomography‑derived skeletal muscle index and radiodensity in patients with gastric cancer after curative gastrectomy.

The association of computed tomography (CT)-derived skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) with postoperative prognosis in patients with gastric cancer (GC) remains unknown. Therefore, the present study aimed to assess the association between SMI and SMD with 5-year overall survival (OS) and recurrence-free survival (RFS) in patients with GC. SMI and SMD were measured preoperatively in patients who underwent gastrectomy. Patients were categorized into Groups 1 (high SMI and SMD), 2 (high SMI or SMD) and 3 (low SMI and SMD). OS and RFS rates were assessed using Kaplan-Meier analysis and the log-rank test. Among 459 patients, OS and RFS rates were significantly lower in the low-SMD group than in the high-SMD group (OS, 83.4% vs. 88.8%, respectively; P=0.04 and RFS, 80.5% vs. 87.2%, respectively; P=0.02). OS and RFS rates were also significantly lower in Group 3 than in Groups 2 and 1 (P=0.006). Multivariate analysis revealed that a low SMI and SMD (Group 3) was a significant independent prognostic factor for OS [hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.17-4.59; P=0.016] and RFS (HR, 2.28; 95% CI, 1.19-4.37; P=0.013). In summary, low SMI and SMD values may be useful postoperative prognostic indicators for patients with GC.

Assessment of Treatment Sequence in Patients With Stage III Breast Cancer

IntroductionStage III breast cancer is defined as locally advanced breast cancer and is treated with curative intent. Historically, overall survival (OS) did not differ based on treatment sequence (neoadjuvant chemotherapy [NAC] followed by surgery versus surgery followed by chemotherapy). Given recent advancements, we examined if treatment sequence may be associated with improved OS in a contemporary cohort of patients with stage III breast cancer. MethodsPatients aged 18-80 years with prognostic stage III breast cancer who received chemotherapy and surgery were selected from the Surveillance, Epidemiology, and End Results database. Patients were stratified by treatment sequence (NAC versus surgery first). Unadjusted OS and breast cancer–specific survival (BCSS) were estimated using the Kaplan–Meier method and compared with log-rank tests. Cox proportional hazards models were used to estimate the association of treatment sequence with OS and BCSS after adjustment for selected covariates. ResultsThe study included 26,573 patients; median follow-up was 62.0 months (95% confidence interval [CI] 61.0-63.0). Patients receiving NAC had a worse OS and BCSS compared to those who underwent surgery first (5-year OS rates 0.66 versus 0.73; 5-year BCSS rates 0.70 versus 0.77; both log-rank P < 0.001). After adjustment for tumor subtype, receipt of NAC (versus surgery first) remained associated with a worse OS (hazard ratio 1.27, 95% CI 1.2-1.34, P < 0.001) and BCSS (hazard ratio 1.35, 95% CI 1.27-1.43, P < 0.001). ConclusionsBased on data from patients treated largely before 2020, undergoing surgery first may be associated with improved survival, even after adjustment for known covariates including tumor subtype. These findings may inform treatment when caring for patients with operable, locally advanced breast cancer.

Beneficial effects of extravascular lung water index-guided volum management in patients with cardiogenic shock

Objective: To evaluate the role of volume management guided by extravascular lung water index(EVLWI) in improving the clinical outcomes and cardiac function for patients with cardiogenic shock. Methods: This study was a single-center, prospective cohort study. Patients with cardiogenic shock admitted to the Department of Cardiovascular Medicine, Shanghai East Hospital from July 2022 to December 2023 were enrolled. Patients were matched 1∶1 by propensity score and divided into EVLWI group and control group. In the control group, the volume management strategy was determined by the attending physician based mainly on conventional factors, including clinical features, biochemical assessments, and certain blood pressure measurements. In EVLWI group, the volume management plan was formulated by integrating conventional factors with EVLWI derived from pulse index continuous cardiac output (PiCCO) monitoring. Baseline clinical data, in-hospital treatment, and hemodynamic data were collected. Major adverse cardiovascular events and cardiac function related parameters were compared at 30 d after treatment between the two groups. Baseline EVLWI levels were compared between the non-survivors and the survivors in the EVLWI group. The receiver operating characteristic curve was plotted to assess the accuracy of baseline EVLWI and central venous pressure in predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, and subgroup analysis was performed according to ischemic/non-ischemic etiology and with/without use of inotropic drugs. Kaplan-Meier curve was used for survival analysis, with log-rank tests comparing all-cause mortality, cardiac death, and readmission rate for heart failure at 30 d after treatment. Results: A total of 200 patients with cardiogenic shock were enrolled, aged (71.35±12.82) years, 144(72%) males, EVLWI group and control group 100 patients each. Compared with the control group, EVLWI group had lower all-cause mortality (16%(16/100) vs. 42%(42/100), log-rank P<0.01), cardiac death (14%(14/100) vs. 34%(34/100), log-rank P<0.01), and readmission rate for heart failure (4%(4/100) vs. 12%(12/100), log-rank P=0.03) at 30 d after treatment. Subgroup analysis showed that EVLWI-guided volume management was associated with lower all-cause mortality at 30 d after treatment in patients with cardiogenic shock of ischemic or non-ischemic etiology and with or without inotropic drugs (all P<0.05). In EVLWI group, baseline EVLWI levels were higher in non-survivors than those in survivors [(15.99±6.47) ml/kg vs.(9.75±2.55) ml/kg, P<0.01]. The baseline EVLWI could predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, with an area under the receiver operating characteristic curve of 0.84 (95%CI: 0.75-0.94, P<0.01), while the baseline central venous pressure had no predicting value (AUC=0.54, 95%CI: 0.40-0.69, P=0.60). The optimal cutoff value of EVLWI in pridicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock was >10.3 ml/kg. With the optimization of hemodynamic parameters, left ventricular ejection fraction was improved in EVLWI group, and serum levels of N-terminal pro-brain natriuretic peptide, creatinine, alanine aminotransferase and lactic acid were decreased (all P<0.05). Conclusion: EVLWI-guided volume management exerts a beneficial effect on therapeutic decision-making and improves clinical outcomes and cardiac function in patients with cardiogenic shock.

Abstract C154: Clinical, genomic, and socioeconomic factors underlying low survival rates from colorectal cancer in African American patients

Abstract Background: Colorectal cancer (CRC) patients of African ancestry (AFR) have higher incidence, higher mortality, and shorter overall survival (OS) than patients of non-African ancestry (non-AFR) in the United States. This disparity is likely due to a combination of clinical, genomic, and socioeconomic factors. We investigated real-world data of patients from a single tertiary cancer center to delineate the contribution of each of those variables. Methods: We analyzed data from 3,995 CRC patients, including 247 AFR and 3,748 non-AFR patients, diagnosed after 2014 and treated at Memorial Sloan Kettering Cancer Center. Every patient had a specimen sequenced with MSK-IMPACT, a targeted DNA sequencing assay that identifies genomic alterations in 341-505 genes. Genetic ancestry was determined using previously published methods by our group. Clinical annotations included sex, age at diagnosis (Dx), stage at Dx, and tumor location. Billing records were used to identify the type of insurance per patient and estimate their Yost Index (YI), a location-dependent socioeconomic status (SES) percentile score based on household incomes, house values, rent, poverty, education, and employment statistics. A multivariate cox proportional hazards model was used to assess the association between clinical variables (stage at Dx, age at Dx, sex, primary tumor location), genomic features (MSI status, BRAF, APC, SMAD4 alterations, chromosome 20Q amplifications), SES (YI) and OS. Propensity score matching (PSM) was performed using all features included in the multivariate model to assess outcome differences after matching for clinical, genomic, and socioeconomic variables. OS was measured in months from time of Dx to last follow-up and compared using the log-rank test. Results: AFR patients had worse OS compared to non-AFR patients (median OS: AFR, 44.9 vs. non-AFR, 64.3, p&amp;lt;0.001). AFR patients were younger at Dx (median 53 vs. 57 yo, p&amp;lt;0.001), had higher rates of right-sided tumors (41.1% vs. 30.2%, p&amp;lt;0.001), and less often had microsatellite unstable (MSI) tumors (5.26% vs 10.0%, p=0.014). Among microsatellite stable cases, AFR patients had a higher frequency of KRAS (57.1% vs. 44.7%, p=0.004) and a lower frequency of BRAF mutations (4.3% vs. 7.7%, p=0.069). Medicaid was more frequent among AFR patients (10.12% vs. 4.87%, p&amp;lt;0.001). AFR patients had lower SES (median YI 42 vs. 17, p&amp;lt;0.001). In a multivariate model accounting for clinical, genomic and socioeconomic features, AFR ancestry remained associated with worse outcomes (HR: 1.35, p = 0.007). AFR patients also had significantly shorter OS than the set of non-AFR patients matched for clinical, genomic, and socioeconomic features (5-yr OS was 31.6% for AFR vs 45.7% for non-AFR, log-rank p-value = 0.014). Conclusions: Colorectal cancer patients of AFR ancestry had significantly shorter OS than patients of other ancestries after accounting for basic clinical, genomic, and socioeconomic variables. Further research is needed in order to understand the causes of this disparity. Citation Format: Sharafudeen D. Abubakar, Henry Walch, Xuechun Bai, Tejiri Agbamu, Michele Waters, Kanika Arora, Farheen Shah, Christopher Fong, Justin Jee, Hannah Williams, Michael F Berger, Karuna Ganesh, Julio Garcia- Aguilar, Nikolaus Schultz, Rona Yaeger, Walid K Chatila, Francisco Sanchez-Vega. Clinical, genomic, and socioeconomic factors underlying low survival rates from colorectal cancer in African American patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C154.

Multi-marker analysis of circulating tumor cells in localized intermediate/high-risk and metastatic prostate cancer

AbstractCirculating tumor cells (CTCs) are an established prognostic marker in metastatic prostate cancer (PrC) but have received little attention in localized high-risk disease. Peripheral blood was obtained from patients with early intermediate and high-risk PrC (n = 15) at baseline, after radiotherapy, and during follow-up, as well as from metastatic PrC patients (n = 23). CTCs were enriched using the microfluidic Parsortix® technology. CTC-related marker were quantified with qPCR and RNA in-situ hybridization (ISH). Positivity and associations to clinical parameters were assessed using McNemar test, Fisher Exact test or log-rank test. The overall positivity was high in both cohorts (87.0% metastatic vs. 66.7% early at baseline). A high concordance of qPCR and RNA ISH was achieved. In metastatic PrC, PSA and PSMA were prognostic for shorter overall survival. In early PrC patients, an increase of positive transcripts per blood sample was observed from before to after radiation therapy, while a decrease of positive markers was observed during follow-up. CTC analysis using the investigated qPCR marker panel serves as tool for achieving high detection rates of PrC patient samples even in localized disease. RNA ISH offers the advantage of confirming these markers at the single cell level. Employing the clinically relevant marker PSMA, our CTC approach can be used for diagnostic purposes to screen patients profiting from PSMA-directed PET-CT or PSMA-targeted therapy.

High-Risk HLA-DQ Mismatches Are Associated With Adverse Outcomes After Lung Transplantation

Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students’ t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients (p = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR (p = 0.03) and CLAD (p = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.

Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab.

Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC). This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab. We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions. Of 44patients, 77.3% were men with median age of 67years. All but 3patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04). ctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.

Total versus Partial Pancreatectomy in Patients with Pancreatic Cancer Arising from Multifocal or Diffuse Intraductal Papillary Mucinous Neoplasia - A Multicenter Observational Study.

To investigate the impact of total pancreatectomy (TP) on oncological outcomes for patients at high-risk of local recurrence or secondary progression in the remnant gland after partial pancreatectomy (PP) for IPMN-associated cancer. Major risk factors for invasive progression in the remnant gland include multifocality, diffuse main duct dilation, and the presence of invasive cancer. In these high-risk patients, a TP may be oncologically beneficial. However, current guidelines discourage TP, especially in elderly patients. This international multicenter study compares TP versus PP in patients with adenocarcinoma arising from multifocal or diffuse IPMN (2002-2022). Log-rank test and multivariable Cox-analysis with interaction analysis was performed to assess overall survival (OS), disease-free survival (DFS), and local-DFS. Of 359 included patients, 162 (45%) were treated with TP, whereas 197 (55%) underwent PP. Despite TP and PP having similar R0-rates (59% vs. 58%, P=0.866), patients undergoing a TP had significantly longer local-DFS compared to PP (P=0.039). However, no difference in OS was observed between the two surgical approaches (P=0.487). In a multivariable analysis, young age (optimal cut-off ≤63.6yrs) was associated with an OS benefit derived from TP (HR:0.44, 95%CI:0.22-0.89), whereas no significant difference was observed in elderly patients (HR:1.24, 95%CI:0.92-1.67, Pinteraction=0.007). Since overall, patients with diffuse or multifocal IPMN with an invasive component do not benefit from TP in terms of OS, the indication for TP may be individualized to young patients who have sufficient life expectancy to benefit from the prevention of secondary progression or local recurrence.

Efficacy and safety of calcineurin inhibitors (CNIs) for septic patients in ICU: a cohort study from MIMIC database

BackgroundSepsis is marked by a dysregulated immune response to infection. Calcineurin inhibitors (CNIs), commonly used as immunosuppressants, have unique properties that may help mitigate the overactive immune response in sepsis, potentially leading to better patient outcomes. This study aims to assess whether CNIs improve prognosis in septic patients and to evaluate any associated adverse reactions.MethodsWe utilized the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2) database to identify septic patients who were treated with CNIs and those who were not. Propensity score matching (PSM) was employed to balance baseline characteristics between the CNI user group and the non-user group. The primary outcome was 28-day mortality, analyzed using the Kaplan-Meier method and Cox proportional hazard regression models to examine the relationship between CNI use and patient survival.ResultsFrom the MIMIC-IV database, 22,517 septic patients were identified. After propensity score matching, a sample of 874 patients was analyzed. The CNI group exhibited a significantly lower 28-day mortality risk compared to the non-user group (HR: 0.26; 95% CI: 0.17, 0.41) in the univariate Cox hazard analysis. Kaplan-Meier survival curves also demonstrated a significantly higher 28- and 365-day survival rate for CNI users compared to non-users (log-rank test p-value = 0.001). No significant association was found between CNI use and an increased risk of new-onset infection (p = 0.144), but an association with mild hypertension (P &amp;lt; 0.001) and liver injury (P &amp;lt; 0.001) was observed.ConclusionThe use of calcineurin inhibitors was associated with reduced short- and long-term mortality in septic patients without an increased incidence of new-onset infections, hyperkalemia, severe hypertension, or acute kidney injury (AKI). However, CNI use may lead to adverse effects, such as liver injury and mild hypertension.

Association of CYP7B1 expression with the prognosis of endometrial cancer: a retrospective study

BackgroundEndometrial cancer (EC) tissues express CYP7B1, but its association with prognosis needs to be investigated.MethodsImmunohistochemistry and image analysis software were used to assess CYP7B1 protein expression in paraffin-embedded endometrial tumor sections. Associations between CYP7B1 and clinical factors were tested with the Wilcoxon rank-sum test. Kaplan-Meier curves were employed to describe survival, and differences were assessed using the log-rank test. Cox regression analysis was used to assess the association between CYP7B1 expression and the prognosis of patients with EC.ResultsA total of 307 patients were enrolled with an average age of 52.6 ± 8.0 years at diagnosis. During the period of follow-up, 46 patients (15.0%) died, and 29 (9.4%) suffered recurrence. The expression of CYP7B1 protein is significantly higher in the cytoplasm than in the nucleus (P < 0.001). Patients aged < 55 years (P = 0.040), ER-positive patients (P = 0.028) and PR-positive patients (P < 0.001) report higher levels of CYP7B1 protein. Both univariate (HR = 0.41, 95% CI: 0.18–0.90, P = 0.025) and multivariate (HR = 0.35, 95%CI:0.16–0.79, P = 0.011) Cox regression analyses demonstrate that high CYP7B1 protein expression predicts longer overall survival (OS). When considering only ER-positive patients (n = 265), CYP7B1 protein expression is more strongly associated with OS (HR = 0.20,95%CI:0.08–0.52, P = 0.001). The 3-year OS and 5-year OS in the low-CYP7B1 subgroup are 81.6% and 76.8%, respectively; while in the high-CYP7B1 subgroup are 93.0% and 92.0%, respectively (P = 0.021).ConclusionsHigh CYP7B1 protein expression predicted longer OS, suggesting that it may serve as an important molecular marker for EC prognosis.

Absolute lymphocyte count predicts efficacy of palbociclib in patients with metastatic luminal breast cancer

BackgroundAbsolute lymphocyte count (ALC) is a predictive and prognostic factor for various tumor types, including breast cancer. Palbociclib is a CDK4/6 inhibitor widely used for the treatment of metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer. However, predictive biomarkers of the efficacy of palbociclib remain unelucidated. We conducted a retrospective study to examine the predictive value of the baseline ALC in patients treated with palbociclib.MethodsThe medical records of patients with ER-positive, HER2-negative breast cancer treated with palbociclib plus hormonal therapy between December 2017 and December 2021 were analyzed retrospectively. The cutoff value of ALC was set at 1800 cells/μL at the initiation of palbociclib treatment. The clinical benefit rate (CBR) was defined as the rate of complete or partial response or stable disease for at least 6 months. Progression-free survival (PFS) rates were estimated using the Kaplan–Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards regression.ResultsAll of the 202 patients were women, with a median age of 59 years and a performance status (PS) of ≤ 2. The median numbers of lines of chemotherapy and endocrine therapy before palbociclib treatment were 0 (range, 0–9) and 1 (range, 0–7), respectively. Fifty-one patients had liver metastases. Forty-six patients tested negative for progesterone receptor (PgR) expression. The median follow-up time was 9.1 months. The CBR was significantly higher in the ALC-high group than in the ALC-low group (79% vs. 60%; P = 0.018). The median PFS was significantly longer in the ALC-high group than in the ALC-low group (26.8 months vs. 8.4 moths, respectively; P = 0.000013). ALC, age, PS, PgR status, prior chemotherapy, prior endocrine therapy, and liver metastasis were entered into the multivariate analysis. ALC was identified as an independent factor for PFS (P = 0.00085), along with liver metastasis (P = 0.0020), PS (P = 0.026), and prior endocrine therapy (P = 0.019).ConclusionALC can serve as a predictor of palbociclib efficacy in patients with metastatic ER-positive, HER2-negative breast cancer.

The prognostic implications of radiologic extranodal extension in the lymph nodes of patients with nasopharyngeal cancer.

Objective: This study was developed to explore the prognostic relevance of radiologic extranodal extension (rENE) in lymph node-positive nasopharyngeal carcinoma (NPC) patients. Materials and methods: A retrospective review of data from 249 eligible patients with NPC was performed, with magnetic resonance imaging scans being used for rENE grading. The prognostic value of rENE was assessed through univariate and multivariate analyses. Results: Log-rank tests revealed significant differences between patients with and without rENE in terms of overall survival, progression-free survival (PFS) and distant metastasis-free survival (DMFS). G2 and G3 patients tended to exhibit worse PFS and DMFS relative to G0/G1 patients (p <0.05). Long-term chemotherapy cycles were associated with significant improvements in the PFS and DMFS of G2 and G3 patients. Conclusion: These results suggest that higher rENE grades (G2/G3) are independently associated with worse survival outcomes among NPC patients, with more aggressive treatment strategies potentially affording greater prognostic benefits to these individuals.

Low UKA implantation volume, comorbidities, male sex, and implantation of constrained TKA are risk factors for septic revision after knee arthroplasty implantation : A register-based study from the German Arthroplasty Register

Periprosthetic joint infection (PJI) is one of the main causes of revision surgeries after total knee arthroplasty (TKA) and unicondylar knee replacement. Patient- and hospital-related risk factors must be evaluated to prevent PJI. This study identifies influencing factors and differences in infection rates between various types of implant. The basis for the data is the German Arthroplasty Register (EPRD). Septic revisions were calculated with the aid of Kaplan-Meier estimates, with septic revision surgery defined as the primary endpoint. Patients with constrained and unconstrained TKA or UKA were analysed using the Holm multiple log-rank test and the Cox proportional hazard model. The 300,998 cases of knee arthroplasty analysed included 254,144 (84.4%) unconstrained TKA, 9993 (3.3%) constrained TKA and 36,861 (12.3%) UKA, with a maximum follow-up of 7 years. After 1 year, the PJI rate was 0.5% for UKA and 2.8% for TKA, whereas after 7 years it was 4.5% for UKA and 0.9% for TKA (p < 0.0001). In constrained TKA, the PJI rate was significantly increased compared with unconstrained TKA (p < 0.0001). After 1 year, the PJI rate was 2.0% for constrained TKA and 0.8% for unconstrained TKA, as well as 3.1% and 1.4% respectively after 7 years. Implantation of a constrained TKA (HR = 2.55), male sex (HR = 1.84), an increased Elixhauser Comorbidity Index score (HR = 1.18-1.56) and an implantation volume of less than 25 UKA per year (HR = 2.15) were identified as risk factors for revision surgeries; an Elixhauser Comorbidity Index score of0 (HR = 0.80) was identified as a preventive factor. A reduced implantation volume and constrained knee arthroplasty are linked to a higher risk of PJI. Comorbidities (increased Elixhauser Comorbidity Index score), male sex and a low UKA-implantation volume were identified as risk factors for PJI. Patients who fulfil these criteria need specific infection prevention measures. Further analyses are required to investigate the potential influence of prevention and risk factor modification. III.

Impact of preoperative inflammatory and nutritional markers on the prognosis of patients with peritoneal metastasis of colorectal cancer

BACKGROUND Identifying patients with peritoneal metastasis (PMs) of colorectal cancer (CRC) who will benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is crucial before surgery. Inflammatory and nutritional indicators play essential roles in cancer development and metastasis. AIM To investigate the association of preoperative inflammatory and nutritional markers with prognosis in patients with CRC-PM. METHODS We included 133 patients diagnosed with CRC-PM between July 2012 and July 2018. Patients’ demographics, overall survival (OS), and preoperative inflammatory and nutritional markers were evaluated. The Kaplan-Meier method and log-rank test were used to estimate differences. RESULTS Of the 133 patients, 94 (70.6%) had normal hemoglobin (Hb) and 54 (40.6%) had a high neutrophil-to-lymphocyte ratio (NLR). The median OS (mOS) was significantly lower for patients with high NLR (7.9 months) than for those with low NLR (25.4 months; P = 0.002). Similarly, patients with normal Hb had a longer mOS (18.5 months) than those with low Hb (6.3 months; P &lt; 0.001). Multivariate analysis identified age, carbohydrate antigen 199 levels, NLR, Hb, and peritoneal cancer index as independent predictors of OS. Based on these findings, a nomogram was constructed, which demonstrated a good capacity for prediction, with a C-index of 0.715 (95% confidence interval: 0.684-0.740). Furthermore, the 1- and 2-year survival calibration plots showed good agreement between predicted and actual OS rates. The areas under the curve for the 1- and 2-year survival predictions of the nomogram were 0.6238 and 0.6234, respectively. CONCLUSION High NLR and low Hb were identified as independent predictive risk factors for poor prognosis in patients with CRC-PM. The established nomogram demonstrated high accuracy in predicting OS for patients with CRC-PM, indicating its potential as a valuable prognostic tool for this patient population.

Abstract PR-21: Temporal stability and chemotherapy responsiveness of classical and basal transcriptional subtypes of pancreatic cancer

Abstract Background: Transcriptional profiling of pancreatic cancers (PC) has defined classical and basal subtypes; basal tumors have worse outcomes. Initial data suggest worse outcomes to FOLFIRINOX (FFX) compared with gemcitabine nab-paclitaxel (GnP) in basal tumors. In addition, it is hypothesized that classical to basal conversion may lead to chemotherapy resistance, although clinical evidence for subtype conversion and subtype specific chemotherapy sensitivity are sparse. Here, we examined the temporal stability and clinical implications of PC transcriptional subtypes in a large, real-world dataset. Methods: We examined patients with metastatic PC, who had outcomes data and RNA sequencing (n=5,335) performed at Caris Life Sciences (Phoenix, AZ). Classical and basal subtypes were identified along a six subtype continuum from strong classical (SC) to strong basal (SB) on either pole using PurIST algorithm. Overall survival (OS) was defined from date of biopsy of metastatic site to date of death or last known contact and estimated using Kaplan-Meier method. Survival was compared between groups using log-rank test and cox proportional hazards regression. Predictors of subtype discordance were assessed in patients who underwent RNA-sequencing of two tumor biopsies using multivariable logistic regression. Results: In patients with metastatic PC, SB tumors (n = 1,579) had significantly worse OS compared to SC tumors (n = 2,118), with a median OS of 5.7 vs. 10.0 months, respectively (hazard ratio [HR] 1.49, 95% confidence interval [CI], 1.39-1.60, p = 2.77e-27) independent of impact of age, gender and mutations in KRAS, TP53, CDKN2A or SMAD4 in cox proportional hazard models. OS was worse in patients with SB tumors who received either 1L GnP [SB (n = 112) vs. SC (n = 178), median OS: 6.0 vs. 10.4 months (HR 1.35 [95% CI, 1.05-1.75], p = 0.02)], or 1L FFX [SB (n = 155) vs. SC (n = 215), median OS: 8.9 vs. 12.5 months (HR 1.35 (95% CI, 1.06-1.72), p = 0.013)]. The prognostic impact of transcriptional subtype within different KRAS-mutant alleles is not well defined. OS was short and not significantly different between the three most frequent KRAS alleles (G12 V/D/R) in SB tumors (median OS, KRAS G12R/V/D: 5.4 vs. 5.4 vs. 5.5 months). In SC tumors, KRAS G12D was associated with a significantly worse OS compared to KRAS G12R (median OS: 8.6 vs. 11.9 months, HR 1.23 (95% CI, 1.04-1.47), p = 0.018). KRAS G12V had a numerically worse survival compared with KRAS G12R in SC tumors (median OS: 9.4 vs. 11.9 months, HR 1.15 (95% CI, 0.96-1.37), p = 0.12). Sixty of 77 cases (78%) maintained their transcriptional subtype between two temporally &amp;/or spatially disparate lesions. The likelihood of transcriptional subtype change was independent of the duration between (p = 0.79) or site of (p = 0.37) the two biopsies. Conclusions: SB subtype is a strong independent predictor of worse outcomes, irrespective of mutant KRAS allele or upfront chemotherapy regimen, and tends to remain stable between biopsies in individual patients Citation Format: Harshabad Singh, Joanne Xiu, Kevin Kapner, Chen Yuan, Raja R Narayan, Matthew Oberley, Alex Farrell, Rishi Surana, Brandon M Huffmann, Kimberly J Perez, James M Cleary, Alexander C Jordan, Andressa Dias Costa, Hannah L Williams, Srivatsan Raghavan, Benjamin Weinberg, Michael J Pishvaian, Rachna T Shroff, Sanjay Goel, Stephanie K Dougan, Jonathan Nowak, David Spetzler, George Sledge, Brian M Wolpin, Andrew J Aguirre. Temporal stability and chemotherapy responsiveness of classical and basal transcriptional subtypes of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-21.

Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer.

Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes. In this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine-cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine-cisplatin followed by radical cystectomy alone (comparison group). Event-free survival was one of two primary end points. Overall survival was the key secondary end point. In total, 533 patients were assigned to the durvalumab group and 530 to the comparison group. The estimated event-free survival at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the durvalumab group and 59.8% (95% CI, 55.4 to 64.0) in the comparison group (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). The estimated overall survival at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the durvalumab group and 75.2% (95% CI, 71.3 to 78.8) in the comparison group (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P = 0.01 by stratified log-rank test). Treatment-related adverse events of grade 3 or 4 in severity occurred in 40.6% of the patients in the durvalumab group and in 40.9% of those in the comparison group; treatment-related adverse events leading to death occurred in 0.6% in each group. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of those in the comparison group. Perioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherapy alone. (Funded by AstraZeneca; NIAGARA ClinicalTrials.gov number, NCT03732677; EudraCT number, 2018-001811-59.).

Increased serum albumin corrected anion gap levels are associated with poor prognosis in septic patients with liver cirrhosis

The prognosis of septic patients with cirrhosis is worse compared to septic patients without cirrhosis. Early and accurate prognosis determination in patients with cirrhosis and sepsis is pivotal for guiding treatment decisions. The aim of this study was to investigate the association between albumin-corrected anion gap (ACAG) and clinical prognosis of patients with sepsis and cirrhosis. This study extracted data of patients with sepsis and cirrhosis from the Medical Information Mart for Intensive Care (MIMIC-IV) database. A total of 1340 patients (64.6% male) were enrolled. After confounders adjusting, elevated ACAG had a significant association with 28-day mortality (HR1.604; 95% CI 1.258–2.048; P < 0.001). Restricted cubic spline revealed that a linear relationship between ACAG and 28-day mortality (P-nonlinear = 0.089, P-overall = 0.001). According to the ROC curve analysis, the ACAG demonstrated a higher area under the curve (AUC) of 0.703 compared to AG (0.675). Kaplan–Meier analysis revealed higher 28-day mortality in high ACAG group (log-rank test, χ^2 = 175.638, P < 0.001). Furthermore, subgroup analysis showed a significant interaction between ACAG and etiology of cirrhosis (P for interaction = 0.014). Therefore, ACAG could provide clinicians with valuable insights for guiding interventions in this high-risk population.

Comparison of efficacy between anti-PD-1 antibody monotherapy and nivolumab plus ipilimumab therapy as first-line immunotherapy for advanced mucosal melanoma in Japanese patients: A single-center, retrospective cohort study.

Mucosal malignant melanoma (MMM) is a rare subtype of malignant melanoma with a more aggressive biological behavior than cutaneous melanoma (CM). Owing to its rarity, it is necessary to accumulate information on treatments, especially in Asians, in whom MMM occurs more frequently than in Caucasians. In this study, we investigated the efficacy and adverse events (AEs) of nivolumab plus ipilimumab therapy (NIVO+IPI) versus immune checkpoint inhibitor (ICI) monotherapy (PD-1) in Japanese patients with MMM. We reviewed patients with advanced or recurrent MMM who received ICIs as first-line systematic therapy between February 2012 and February 2024 at the Shizuoka Cancer Center. We enrolled a total of 57 patients: 10 (17.5%) were treated with NIVO+IPI, and 47 (82.5%) were treated with PD-1 as first-line systemic therapy. Objective response rates (ORR) did not differ significantly between the NIVO+IPI and PD-1 groups (40.0% vs 27.7%; p = 0.176). There was also no statistically significant difference in progression-free survival (PFS) (median PFS time: 4.3 months vs 9.9 months, log-rank test, p = 0.578) or overall survival (OS) (median OS time: 33.1 months vs. 22.8 months, log-rank test, p = 0.697) between the two groups. However, regarding AEs, grade ≥3 AEs leading to discontinuation of first-line treatment occurred in 80% of patients in the NIVO+IPI group and in 22.6% of patients in the PD-1 group (p = 0.002). No difference was found in the efficacy of NIVO+IPI therapy and anti-PD-1 antibody monotherapy as the first-line treatment for MMM in Japanese patients, but an increase in AEs was observed with combination therapy. This study suggests that patients with MMM may receive less benefit from NIVO+IPI than from PD-1.