Restricted Mean Survival Time Research Articles

Development of graded prognostic assessment for breast Cancer brain metastasis incorporating extracranial metastatic features: a retrospective analysis of 284 patients

BackgroundBreast cancer brain metastasis (BCBM) is associated with poor survival outcomes and reduced quality of life. The Graded Prognostic Assessment (GPA) score model serves as a well-established tool for predicting the prognosis of BCBM. Notably, the presence of extracranial metastasis (ECM) is considered as a significant prognostic factor in the breast GPA model. This study aims to further refine other features of ECM to enhance the prognostic prediction for BCBM.MethodsThis study included all inpatients diagnosed with BCBM at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2010 to July 2021. Baseline characteristics of patients were compared based on features of ECM, including the presence, number, location, and control status of metastases. Overall survival (OS) were compared using the Kaplan–Meier method with log-rank tests. Cox regression analyses were conducted to identify significant prognostic factors. The aforementioned ECM features were incorporated into the original Breast-GPA model to enhance its prognostic accuracy. The concordance index (C-index) and restricted mean survival time (RMST) were utilized to evaluate and compare the predictive accuracy of the updated and original survival models.Results284 patients with BCBM were included in the study. Kaplan–Meier survival curves suggested that patients without ECM when diagnosed with BCBM showed better survival (p = 0.007). In the subgroups with ECM, more than 3 organs involved, both bone and visceral metastasis and progressive ECM portended dismal OS (p = 0.003, 0.001 and <0.001). Multivariate analysis demonstrated that molecular subtype, presence of ECM, and number of brain metastasis significantly influenced OS after BCBM. By modifying the current GPA model to include more precise characteristics of ECM, the predictive accuracy was further enhanced as indicated by the C-index and RMST curve.ConclusionsMore ECM sites, both bone and visceral invasion and uncontrolled ECM were dismal prognostic factors for survival outcomes of BCBM patients. A new Breast-GPA model with better predictive effect was constructed.

Impact of complementary health approaches on opioid prescriptions among veterans with musculoskeletal disorders – A retrospective cohort study

To examine whether complementary and integrative health approaches mitigate opioid prescriptions for pain and whether the relationship differs by post-dramatic stress disorder (PTSD) diagnosis, we followed 1,993,455 Veterans with musculoskeletal disorders during 2005–2017 using Veterans Healthcare Administration electronic health records. Complementary and integrative health (CIH) approaches were defined as ≥ 1 primary care visits for meditation, Yoga, and acupuncture etc using natural language processing. Opioid prescriptions were ascertained from pharmacy dispensing records. A propensity score was estimated and used to match one control Veteran to each CIH recipient. Over the 2-year follow-up period after the index diagnosis, 140,902 (7.1 %) Veterans received ≥ 1 modalities. Among the matched analytic sample (272,296 Veterans), the likelihood of dispensing opioid prescriptions was significantly lower for Veterans in the CIH group than their controls [adjusted hazard ratio (aHR), 0.45 (95 % Confidence Intervals (CI): 0.44–0.46)]. The association did not differ between Veterans with [aHR: 0.46 (95 % CI: 0.45–0.47)] and without [aHR: 0.44 (95 % CI: 0.43–0.45)] PTSD. In sensitivity analyses, the exposure group had 3.82 (95 % CI: 3.76–3.87) months longer restricted mean survival time to opioid initiation, 2 % (95 % CI: 4 %–1 %) lower morphine equivalent and 17 % lower total days’ supply (95 % CI: 18 %–16 %). The relationship remains significant but was attenuated after eliminating waiting time for the exposure group (aHR, 0.63 (95 % CI: 0.62–0.64)). These observations suggest that CIH approaches may help reduce opioid prescriptions for Veterans with musculoskeletal disorders and related pain. The impact of the timing of receiving such approaches warrants further investigation. PerspectiveThis article presents a quasi-experimental investigation into potential benefit of complementary and integrative health approaches (CIH) on de-prescribing opioids. The findings may potentially help clinicians who are seeking non-pharmacological alternative options to manage patient pain and opioid dependence”.

Sensitivity analysis for unmeasured confounding in estimating the difference in restricted mean survival time.

The difference in restricted mean survival time has been increasingly used as an alternative measure to the hazard ratio in survival analysis. Although some statistical methods have been developed for estimating the difference in restricted mean survival time adjusted for measured confounders in observational studies, the impact of unmeasured confounding on the estimate has rarely been assessed. We develop a novel sensitivity analysis for the estimate of the difference in restricted mean survival time with respect to unmeasured confounding. After formulating the sensitivity analysis problem as an optimization problem, we explain how to obtain the sensitivity range of the difference in restricted mean survival time efficiently and assess its uncertainty using the percentile bootstrap confidence interval. Analytic results are provided for some important survival settings. Simulation studies show that the proposed methods perform well in various settings. We illustrate the proposed sensitivity analysis method by analyzing data from the German Breast Cancer Study Group study.

Causal effect estimation in survival analysis with high dimensional confounders.

With the ever advancing of modern technologies, it has become increasingly common that the number of collected confounders exceeds the number of subjects in a data set. However, matching based methods for estimating causal treatment effect in their original forms are not capable of handling high-dimensional confounders, and their various modified versions lack statistical support and valid inference tools. In this article, we propose a new approach for estimating causal treatment effect, defined as the difference of the restricted mean survival time (RMST) under different treatments in high-dimensional setting for survival data. We combine the factor model and the sufficient dimension reduction techniques to construct propensity score and prognostic score. Based on these scores, we develop a kernel based doubly robust estimator of the RMST difference. We demonstrate its link to matching and establish the consistency and asymptotic normality of the estimator. We illustrate our method by analyzing a dataset from a study aimed at comparing the effects of two alternative treatments on the RMST of patients with diffuse large B cell lymphoma.

The application of photodynamic therapy in recurrent genital herpes

BackgroundFrequently recurrence of genital herpes imposes significant physical and psychological burdens on patients, while existing treatments are often ineffective in preventing recurrence. Previous studies have indicated that photodynamic therapy (PDT) showed promising outcomes in the treatment of labial herpes simplex virus (HSV) infections; however, its efficacy for genital herpes remained unclear. MethodThe study screened patients with genital herpes at Daping Hospital from July 2020 to May 2024. Patients were divided into two groups based on whether they received PDT treatment. Over a one-year follow-up period, patients' healing time and recurrence rates were compared between the two groups. The cumulative incidence of recurrence and restricted mean survival time (RMST) were used to assess outcomes. Propensity score matching (PSM) was employed to minimize bias. ResultA total of 41 patients enrolled in our study, with 8 (19.5%) received PDT. The non-PDT group exhibited a slower skin lesion healing time, averaging at 7.2 days compared to 5.4 days in the PDT group. A significant difference was observed in the cumulative incidence of recurrence between the PDT and non-PDT groups (37.5% versus 71.4%) after PSM. The RMST in the PDT group was 9.94 days, compared to 5.13 days in the non-PDT group before PSM, and 4.14 after PSM. ConclusionOur study demonstrated that the PDT effectively reduced lesion recovery time and delayed recurrences of genital herpes. We recommend considering PDT as a potential treatment option for patients with recurrent genital herpes.

Impact of early palliative care referral in patients with locally advanced and metastatic GI/lung cancer.

201 Background: Early palliative care improves quality of life and survival in patients with metastatic NSCLC. As a result, ASCO recommends early palliative care integration in patients with metastatic cancer. However, generalizing the benefits outside of a clinical trial may be difficult due to selection bias of patients that opt into palliative care due to advanced symptom burden and real-world resource constraints. Therefore, the benefits of this in real-world practice may not be realized. We aimed to evaluate early vs late palliative care referral impact on unplanned hospital visits and survival among GI and lung cancer patients at a large health system cancer center. Methods: The study design was a retrospective, single health system, review of patients treated at Orlando Health from 2021-2022.156 patients of all stage GI and Lung cancers were included. For these patients, early referral was defined as receiving a palliative referral within 8 weeks of cancer diagnosis. Any referral later than this was considered late and it was possible for patients to opt out of referral. Our main outcomes were unplanned hospital visits and survival. To compare the rates of these between palliative care referral groups, a multivariable negative binomial regression model was fitted. To assess any differences in survival, a multivariable cox hazard regression model was fitted. These were adjusted for age, sex, diagnosis, stage, ECOG, race, and insurance. Results: Patients with any palliative care referral had increased unplanned hospital visits and shorter survival than patients who did not have referrals. Specifically, patients with no palliative care referrals had a 62% lower relative rate of unplanned hospital visits compared to patients with early referral (RR = 0.38 [0.22-0.66], p&lt;0.001). And patients with any time referral had approximately 8 months lower restricted mean survival times (RMST) when followed for 2 years for stage 1-3 cancers than patients receiving no palliative care (14 vs 22 month RMST; stage x palliative care interaction, p &lt;0.05). In contrast, stage 4 patients had similar survival of ~14-month RMST when followed for 2 years regardless of referral. Conclusions: In real world practice palliative care referral was associated with increased unplanned hospital visits. Additionally, in this retrospective review, palliative care referral was not found to confer a survival advantage in gastrointestinal and Lung cancer patients. We postulate that this is related to selection bias in the opt in approach to palliative care referral biasing towards a sicker population with higher symptom burden and comorbidities. Our future prospective study will build upon this work through expansion of palliative care services and to better evaluate patient co-morbidities. Our goal is to increase utilization of palliative care for patients with GI and lung malignancies as part of a multidisciplinary integrative approach.

Intra-arterial chemotherapy combined with BCG immunotherapy is more effective than intra-arterial chemotherapy plus intravesical chemotherapy or standard BCG immunotherapy in preventing the recurrence and progression of high-risk non–muscle-invasive bladder cancer

BackgroundUp to 45% of patients with high-risk non–muscle-invasive bladder cancer (NMIBC) will not benefit from adjuvant intravesical instillation. We aimed to introduce intra-arterial chemotherapy (IAC) to existing intravesical treatment and evaluate its feasibility and safety. Materials and methodsWe collected data from 170 patients who had been diagnosed with high-risk NMIBC and underwent transurethral resection of bladder tumor (TURBT) over the last 5 years. Twenty-seven patients were excluded according to specific exclusion criteria. The remaining 143 patients were divided into 3 groups according to their treatment: intravesical instillation of Bacillus Calmette – Guerin (BCG), BCG+ intra-arterial chemotherapy (IAC), and intravesical chemotherapy (IVC)+IAC groups. All groups received standard intravesical instillation of BCG or chemotherapeutic agents. In contrast, both the BCG+IAC and IVC+IAC groups received four courses of IAC (injection of cisplatin [60 mg/m2] and epirubicin [50 mg/m2] in the internal iliac arteries via Seldinger's percutaneous technique). ResultsThe median follow-up time was 47 months, ranging from 20 to 60 months. The restricted mean survival time (RMST), which represents the recurrence and progression rate of the BCG+IAC group, differed significantly when compared with the BCG group (P = 0.029 and 0.004, respectively) and the IVC+IAC group (P = 0.004 and 0.006, respectively). Kaplan-Meier plots revealed that the recurrence and progression-free survival of the BCG+IAC group were significantly higher than the BCG and IVC+IAC groups (P = 0.033 and 0.028, respectively). In contrast, the BCG and IVC+IAC groups showed similar RMST (P = 0.156 and 0.935, respectively), recurrence (P = 0.627), and progression-free (P = 0.931) survival. A small proportion of patients (20%) suffered from the adverse effects of IAC while 65% suffered from adverse reactions to intravesical instillation. Most adverse effects were ranked as grade I or II according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. ConclusionAnalysis showed that tumor recurrence and progression rate in the BCG+IAC group was lower than the BCG and IVC+IAC groups while patients in the IVC+IAC group suffered from milder adverse effects in cystitis and flu-like symptoms. Our findings may provide a new perspective for urologists when treating patients with high-risk NMIBC.

Slipping Away: Slippage in Hazard Ratios Over Datacuts and Its Impact on Immuno-oncology Combination Economic Evaluations

ObjectivesThis study examines the impact of slippage in hazard ratios (tending toward the null over subsequent datacuts) for overall survival for combination treatment with a PD-(L)-1 inhibitor and a tyrosine kinase inhibitor in advanced renal cell carcinoma. MethodsFour trials’ Kaplan-Meier curves were digitized over several datacuts and fitted with standard parametric curves. Accuracy and consistency of early data projections were calculated versus observed restricted mean survival time and fitted lifetime survival from the longest follow-up datacut. The change in economically justifiable price (eJP) was calculated fitting the same curve to both arms, using an assumed average utility of 0.7 and willingness-to-pay threshold of £30 000 per quality-adjusted life-year. The eJP represents the lifetime justifiable price increment for the new treatment, including differences in drug-, administration-, and disease-related costs. ResultsSlippage in hazard ratios was observed in trials with longer follow-up, potentially influenced by subsequent PD-(L)-1 use after tyrosine kinase inhibitor monotherapy, early stoppage of PD-(L)-1, and development of resistance. Lognormal and log-logistic curves were more likely to overpredict the observed result; Gompertz and gamma underpredicted. Statistical measures for goodness of fit did not reliably predict the restricted mean survival time. Large differences in incremental mean life-years were observed between even the penultimate and final datacuts for most of the fitted curves, meaningfully affecting the eJP. ConclusionsThis work demonstrates the challenge in predicting treatment benefits with novel therapies using immature data. Incorporating information on the impact of subsequent treatment is likely to play a key role in improving predictions.

Incidence, Risk Factors, Organism Types, and Outcomes of Catheter-Related Bloodstream Infections in Hemodialysis Patients.

Background Patients undergoing hemodialysis for End-Stage Renal Disease (ESRD) are at risk for Hemodialysis Catheter-Related Bloodstream Infections (CRBSIs). This study evaluates the incidence, risk factors, organism types, and outcomes of CRBSI in adult patients on maintenance hemodialysis at King Faisal Hospital, Rwanda. Methods This was a prospective cohort study of adult patients with end-stage renal disease undergoing hemodialysis via central venous hemodialysis catheters at King Faisal Hospital, Rwanda. Upon receiving the IRB approval, 81 eligible patients, women, and men aged between 19 and 74, were enrolled. Restricted Mean Survival Time (RMST) analysis evaluated the risk factors for CRBSI. The statistical significance was determined using p-values, with a cut-off of 0.05. Results The incidence of CRBSI was found to be 0.78 episodes per 1,000 catheter-days. Acute hemodialysis catheter type and anemia were associated with increased risk for CRBSI, with a P-value less than 0.05. In addition, all CRBSI cases were due to bacteria, with 52.63% gram-negative and 47.37% gram-positive. Out of 19 CRBSI events,nine cases (47.37%) required hospitalization with a median duration of seven days. Approximately half of the CRBSIs required catheter removal. No metastatic infection or death was noted. Conclusion The present study demonstrated that our hemodialysis unit has an incidence of 0.78 episodes per 1,000 catheter-days. Catheter type and anemia were significantly associated with CRBSI.

Tailoring nonsurgical therapy for elderly patients with head and neck squamous cell carcinoma: A deep learning-based approach.

To assess deep learning models for personalized chemotherapy selection and quantify the impact of baseline characteristics on treatment efficacy for elderly head and neck squamous cell carcinoma (HNSCC) patients who are not surgery candidates. A comparison was made between patients whose treatments aligned with model recommendations and those whose did not, using overall survival as the primary metric. Bias was addressed through inverse probability treatment weighting (IPTW), and the impact of patient characteristics on treatment choice was analyzed via mixed-effects regression. Four thousand two hundred seventy-six elderly HNSCC patients in total met the inclusion criteria. Self-Normalizing Balanced individual treatment effect for survival data model performed best in treatment recommendation (IPTW-adjusted hazard ratio: 0.74, 95% confidence interval [CI], 0.63-0.87; IPTW-adjusted risk difference: 9.92%, 95% CI, 4.96-14.90; IPTW-adjusted the difference in restricted mean survival time: 16.42 months, 95% CI, 10.83-21.22), which surpassed other models and National Comprehensive Cancer Network guidelines. No survival benefit for chemoradiotherapy was seen for patients not recommended to receive this treatment. Self-Normalizing Balanced individual treatment effect for survival data model effectively identifies elderly HNSCC patients who could benefit from chemoradiotherapy, offering personalized survival predictions and treatment recommendations. The practical application will become a reality with further validation in clinical settings.

General Population Mortality Adjustment in Survival Extrapolation of Cancer Trials: Exploring Plausibility and Implications for Cost-Effectiveness Analyses in HER2-Positive Breast Cancer in Sweden.

In economic evaluations of novel therapies, assessing lifetime effects based on trial data often necessitates survival extrapolation, with the choice of model affecting outcomes. The aim of this study was to assess accuracy and variability between alternative approaches to survival extrapolation. Data on HER2-positive breast cancer patients from the Swedish National Breast Cancer Register were used to fit standard parametric distribution (SPD) models and excess hazard (EH) models adjusting the survival projections based on general population mortality (GPM). Models were fitted using 6-y data for stage I and II, 4-y data for stage III, and 2-y data for stage IV cancer reflecting an early data cutoff while maintaining sufficient events for comparison of model estimates with actual long-term outcomes. We compared model projections of 15-y survival and restricted mean survival time (RMST) to 15-y registry data and explored the variability between models in extrapolations of long-term survival. Among 11,224 patients compared with the observed registry 15-y RMST estimates across the disease stages, EH cure models provided the most accurate estimates in patients with stage I to III cancer, whereas EH models without cure most closely matched survival in patients with stage IV cancer, in which cure assumption was less plausible. The Akaike information criterion-averaged model projections varied as follows: -8.2% to +5.3% for SPD models, -4.9% to +5.2% for the EH model without a cure assumption, and -19.3% to -0.2% for the EH model with a cure assumption. EH models significantly reduced between-model variance in the predicted RMSTs over a 50-y time horizon compared with SPD models. EH models may be considered as alternatives to SPD models to produce more accurate and plausible survival extrapolation that accounts for general population mortality. Excess hazard (EH) methods have been suggested as an approach to incorporate background mortality rates in economic evaluation using survival extrapolation.We highlight that EH models with or without a cure assumption can produce more accurate survival projections and significantly reduce between-model variability in comparison with standard parametric distribution models across cancer stages.EH models may be a preferred modeling method to reduce model uncertainty in health economic modeling since models that would otherwise have produced implausible extrapolations are constrained by the EH framework.Reduced uncertainty in economic evaluations will enhance the application of evidence-based health care decision making.

COVID-19 Policy Decisions in Manitoba and the Experiences of the Red River Métis: A partnership-based, whole-population linked administrative data study

Systematically marginalized populations, like Red River Métis, have been greatly affected by COVID-19. Manitoba’s Indigenous COVID-19 vaccine policy initially delayed prioritization of Métis. Our research team, which included Métis partners, examined the consequences of these decisions (COVID-19 infections, health service use, vaccine uptake) among Métis, and how earlier prioritization could have improved outcomes. This retrospective cohort study linked data from the Métis Population Database to whole-population COVID testing and vaccination data, and administrative data on health service use. Restricted mean survival time models tested whether vaccination uptake differed between Métis and all other Manitobans (AOM), adjusting for sociodemographic characteristics and comorbidities. A Bayesian model will simulate how prioritization of Métis for vaccination two weeks earlier could have impacted infections. Cumulative prevalence of COVID-19 infection rates were similar among Métis and AOM until May 2021 when rates became higher among Métis. Between May and December 2021, rates of first vaccination were lower among Metis than AOM, as were second vaccination rates between July and November 2021. Métis were more likely than AOM to be hospitalized due to Covid-19 between March and August 2021 and visit physicians for COVID related reasons from October 2020 to Feb 2021 and November 2021 to March 2022. Our analyses simulated what would have occurred had Métis been prioritized for vaccination two weeks before AOM, alongside other Indigenous peoples. Understanding the experiences of Métis relative to AOM is critical to identifying public health strategies which close gaps in vaccine uptake and infections.

Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial

There is an unmet need for second-line and third-line treatments that are effective and tolerable for advanced or metastatic non-small-cell lung cancer (NSCLC) with no driver mutations. In this phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial, we enrolled patients from 58 medical centres in Australia, China, and the USA. Eligible patients were adults with epidermal growth factor receptor (EGFR) wild-type NSCLC who had progressed after first-line platinum-based therapy. Patients were randomly assigned (1:1) using an independent stratified randomisation schedule with a block size of four to receive intravenous docetaxel 75 mg/m2 on day 1 and either plinabulin (30 mg/m2) or placebo on days 1 and 8 in 21-day cycles until progression, unacceptable toxic effects, withdrawal, or death. The primary endpoint was overall survival (OS) in the intention-to-treat (ITT) population. Safety was analysed in all patients who had received at least one dose of study drug or placebo. This trial is registered with ClinicalTrials.gov (NCT02504489) and is now closed. Between Nov 30, 2015, and Jan 6, 2021, 919 patients were screened for inclusion. 360 patients were excluded, and 559 were enrolled and randomly assigned to receive either docetaxel and plinabulin (n=278) or docetaxel and placebo (n=281). 406 (73%) of 559 patients were male, 153 (27%) were female, and 488 (87%) were Asian. Median OS was 10·5 months (95% CI 9·34-11·87) in the plinabulin group compared with 9·4 months (8·38-10·68) in the control group (stratified HR 0·82, 95% CI 0·68-0·99; p=0·0399). Mean OS was 15·08 months (13·42-16·74) in the plinabulin group compared with 12·77 months (11·45-14·10) in the placebo group using restricted mean survival time analysis (difference 2·31 months, 95% CI 0·18-4·44; p=0·0332). Treatment-emergent adverse events occurred in 273 (>99%) of 274 patients in the plinabulin group and 276 (99%) of 278 patients in the control group. Grade 3 or 4 gastrointestinal disorders occurred more frequently in the plinabulin group than in the placebo group, with the most frequent being diarrhoea (24 [9%] of 274 patients vs three [1%] of 278) and vomiting (six [2%] vs one [<1%]), as did transient grade 3 hypertension (50 [18%] vs eight [3%]). Treatment-emergent death was reported in 12 patients (4%) in the plinabulin group and ten patients (4%) in the placebo group. Plinabulin plus docetaxel significantly improved OS as second-line and third-line treatment in patients with advanced or metastatic EGFR wild-type NSCLC and could be considered as a new treatment option in this population. BeyondSpring Pharmaceuticals.

Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer: reconstructed patient-level meta-analysis of randomized clinical trials.

Neoadjuvant treatment has shown promising results in patients with borderline resectable pancreatic ductal adenocarcinoma. The potential benefits of neoadjuvant treatment on long-term overall survival in patients with resectable pancreatic ductal adenocarcinoma have not yet been established. The aim of this study was to compare long-term overall survival of patients with resectable pancreatic ductal adenocarcinoma based on whether they received neoadjuvant treatment or underwent upfront surgery. A systematic review including randomized clinical trials on the overall survival outcomes between neoadjuvant treatment and upfront surgery in patients with resectable pancreatic ductal adenocarcinoma was conducted up to 1 August 2023 from PubMed, MEDLINE and Web of Science databases. Patient-level survival data was extracted and reconstructed from available Kaplan-Meier curves. A frequentist one-stage meta-analysis was employed, using Cox-based models and a non-parametric method (restricted mean survival time), to assess the difference in overall survival between groups. A Bayesian meta-analysis was also conducted. Five randomized clinical trials comprising 625 patients were included. Among patients with resectable pancreatic ductal adenocarcinoma, neoadjuvant treatment was not significantly associated with a reduction in the hazard of death compared with upfront surgery (shared frailty HR 0.88, 95% c.i. 0.72 to 1.08, P = 0.223); this result was consistent in the non-parametric restricted mean survival time model (+2.41 months, 95% c.i. -1.22 to 6.04, P < 0.194), in the sensitivity analysis that excluded randomized clinical trials with a high risk of bias (shared frailty HR 0.91 (95% c.i. 0.72 to 1.15; P = 0.424)) and in the Bayesian analysis with a posterior shared frailty HR of 0.86 (95% c.i. 0.70 to 1.05). Neoadjuvant treatment does not demonstrate a survival advantage over upfront surgery for patients with resectable pancreatic ductal adenocarcinoma.

Geriatric conditions and invasive management in frail patients with NSTEMI. A subgroup analysis of a randomized clinical trial

Introduction and objectivesInvasive management in frail patients with non–ST-segment elevation myocardial infarction (NSTEMI) remains controversial. We investigated the impact of various geriatric conditions. MethodsThe MOSCA-FRAIL trial included 167 adults aged ≥ 70 years with frailty (Clinical Frailty Scale [CFS] ≥ 4 points) and NSTEMI, who were randomized to either an invasive (n=84) or conservative (n=83) strategy. In addition to frailty, we measured activities of daily living (Barthel index), cognitive impairment (Pfeiffer test), and comorbidities (Charlson index). The primary endpoint was the difference (invasive minus conservative) in restricted mean survival time (RMST) for all-cause mortality at a median follow-up of 3.9 years. ResultsA total of 93 patients died. The RMST difference favored invasive management at the CFS 25th percentile (CFS=4; 157 days, 95%CI, 18-295; P=.027), which changed to a nonsignificant effect at the 50th and 75th percentiles. The RMST difference remained nonsignificant, irrespective of the severity of other geriatric assessments. In time-to-event analysis, invasive management was associated with an initially lower life expectancy, peaking at around 1 year, among all subgroups. However, patients with CFS=4 experienced a benefit at the end of follow-up (181 days, 95%CI, 19-343), whereas those with CFS >4 did not (−16 days, 95%CI, −217 to 186; interaction P=.16). Subgroups defined by other geriatric markers showed a similar time-dependent trend, albeit with weaker statistical interaction. ConclusionsAmong adults with frailty and NSTEMI, the CFS might be useful for evaluating the relative risks and benefits of invasive management. A CFS >4 could serve as a valuable threshold for decision-making.

Re-exploration for bleeding and long-term survival after adult cardiac surgery: a meta-analysis of reconstructed time-to-event data.

Postoperative bleeding requiring re-exploration is a serious complication that occurs in 2.8-4.6% of patients undergoing cardiac surgery. Re-exploration has previously been associated with a higher risk of short-term mortality. However, a comprehensive analysis of long-term outcomes after re-exploration for bleeding has not been published. The authors performed a systematic, three databases search to identify studies reporting long-term outcomes in patients who required re-exploration for bleeding after cardiac surgery compared to patients who did not, with at least 1-year of follow-up. Long-term survival was the primary outcome. Secondary outcomes were operative mortality, myocardial infarction, stroke, renal and respiratory complications, and hospital length of stay. Random-effects models was used. Individual patient survival data was extracted from available survival curves and reconstructed using restricted mean survival time. Six studies totaling 135456 patients were included. The average follow-up was 5.5 years. In the individual patient data, patients who required re-exploration had a significantly higher risk of death compared with patients who did not [hazard ratio (HR): 1.21; 95% CI: 1.14-1.27; P <0.001], which was confirmed by the study-level survival analysis (HR: 1.32; 95% CI: 1.12-1.56; P <0.01). Re-exploration was also associated with a higher risk of operative mortality [odds ratio (OR): 5.25, 95% CI: 4.74-5.82, P <0.0001], stroke (OR: 2.05, 95% CI: 1.72-2.43, P <0.0001), renal (OR: 4.13, 95% CI: 3.43-4.39 P <0.0001) respiratory complications (OR: 3.91, 95% CI: 2.96-5.17, P <0.0001), longer hospital length of stay (mean difference: 2.69, 95% CI: 1.68-3.69, P <0.0001), and myocardial infarction (OR: 1.85, 95% CI: 1.30-2.65, P =0.0007). Postoperative bleeding requiring re-exploration is associated with lower long-term survival and increased risk of short-term adverse events including operative mortality, stroke, renal and respiratory complications, and longer hospital length of stay. To improve both short-term and long-term outcomes, strategies to prevent the need for re-exploration are necessary.

Sex-mismatching in isolated heart transplantation confers no postoperative risk

BackgroundFor heart transplantation, optimal donor-recipient matching is an important factor in the ongoing development of the United Network for Organ Sharing (UNOS) continuous distribution framework. Donor-recipient sex-mismatch has decreased since the 1990s, but this may be related to the risk posed by size mismatching, particularly when donor hearts are undersized. Thus, the impact of sex-mismatching, controlling for other factors including size mismatch, is uncertain. MethodsAdult first-time, isolated heart transplant patients from the UNOS database between October 1, 1987 and December 31, 2022 were analyzed. Cohorts were separated into male and female recipients. Propensity score matching on known preoperative risk factors was performed. Equivalence testing via Two One-Sided Testing (TOST) was performed to assess between-arm equivalence in postoperative outcomes. Survival differences were measured by the between-arm ratio of Restricted Mean Survival Time and binary outcome differences by the Odds Ratio (OR). ResultsIn the propensity matched cohort, we found significant equivalence between arms in both male (TOST P<0.001) and female (TOST P<0.001) recipients for overall survival at all temporal endpoints, postoperative treatment for rejection within one year, and pre-discharge dialysis. ConclusionsSex-mismatch in isolated heart transplantation confers no additional risk to postoperative outcomes when controlling for other factors, including size mismatch. Consequently, sex-mismatch should not factor into individual assessments of organ acceptance or be incorporated into any national organ allocation policy. Increasing the acceptance of sex-mismatched donors has the potential to expand the donor pool and increase female donor utilization.

731: Assessing metastasis-directed therapy in oligometastatic disease using restricted mean survival time

731: Assessing metastasis-directed therapy in oligometastatic disease using restricted mean survival time

Comparative analysis among therapeutic modalities in ruptured hepatocellular carcinoma and identification of imaging predictors for survival

BackgroundSpontaneous rupture of hepatocellular carcinoma (rHCC) poses a life-threatening complication with a mortality rate of 25–75%. Treatment aims at achieving hemostasis and includes options such as trans-arterial embolization, perihepatic packing, and hepatic resection. The optimal treatment remains a subject of debate. Our retrospective review evaluates these treatments and investigates imaging’s role in prognosis for rHCC patients.PurposeWe aimed to compare survival outcomes among rHCC patients who received transarterial embolization (TAE), surgery (perihepatic packing, hepatectomy), or best supportive care (BSC), while also identifying predictive imaging factors in these patients.Materials and methodsAll patients diagnosed with rHCC and admitted to Maharaj Nakorn Chiangmai Hospital between January 2012 and December 2021 were included. We reviewed clinical features, imaging results, treatment modalities, and outcomes. In order to balance pretreatment confounders, inverse probability treatment weighting (IPTW) was employed. Flexible parametric survival regression was utilized to compare survival outcomes and identify imaging factors predicting the survival of rHCC patients. Hazard ratios (HR) and the difference in restricted mean survival time (RMST) were reported.ResultAmong the 186 rHCC patients included, we observed 90-day and 1-year mortality rates of 64% and 84%, respectively. Both the TAE and surgery groups exhibited significantly lower 1-year mortality rates compared to BSC. The HR were 0.56 (95% CI 0.33–0.96) for TAE and 0.52 (95% CI 0.28–0.95) for surgery compared to BSC. Both the TAE and surgery also significantly extended the 1-yeaar life expectancy post-initial treatment when compared to BSC, with an RMST difference of + 55.40 days (95% CI 30.18–80.63) for TAE vs. BSC and + 68.43 days (95% CI 38.77–98.09) for surgery vs. BSC. The presence of active contrast extravasation and bleeding in both lobes were independent prognostic factors for 1-year survival.ConclusionsTAE and surgical treatments provide comparable survival benefits for rHCC patients, extending survival time by approximately 2 months compared to best supportive care. We strongly recommend active management for all rHCC patients whenever possible.

Estimation of change-point in the covariate effects on restricted mean survival time

The restricted mean survival time (RMST) emerges as a crucial summary metric in survival analysis. In some cases, certain covariates may have a varying impact on RMST at one specific change-point. For instance, consider studies focusing on women’s health, where a notable shift in a patient’s lifespan might occur when the age at menopause surpasses a particular cutoff value. To tackle this complex phenomenon, we consider a regression analysis of RMST with change-point in the covariate effects. This involves building a generalized linear model that directly captures the relationship between RMST and associated covariates that may have a change-point. Using the smoothed estimating equation with pseudo-observations, we obtain parameter estimators and establish the large sample properties. Finally, we assess the finite sample performance of the proposed method through simulation studies and apply it to real data examples from primary biliary cirrhosis and rectal cancer studies.