Kaplan-Meier Product Limit Estimator Research Articles

Representativeness of race, ethnicity and social determinants of health in patients with advanced non-small cell lung cancer via linkage of real-world electronic health records, administrative claims, and consumer financial data.

e13559 Background: Social determinants of health (SDOH) are both drivers of health disparities and barriers to clinical research participation, particularly among historically underserved or marginalized populations. Using real-world data (RWD), diversity plans in cancer clinical trials frequently aim to reduce disparities and improve representation. Our aim was to describe the representativeness of patients with advanced non-small cell lung cancer (aNSCLC) with respect to race, ethnicity and person-level SDOH in a curated electronic health record (EHR) database. Methods: This was a retrospective cohort study of individuals diagnosed with aNSCLC between 2016–2022 in a US-based oncology EHR database (ConcertAI). Information on person-level SDOH was derived from linkage of curated EHR data to administrative claims and consumer financial data. These data were also compared to a sample of patients diagnosed with first primary NSCLC from the Surveillance, Epidemiology, and End Results (SEER) Program and American Community Survey (ACS), where possible. The Kaplan-Meier product limit estimator was used to compare time from advanced diagnosis to treatment initiation. Results: From an overall sample of 17,772 patients with aNSCLC, a total of 10,390 patients had 1 or more SDOH characteristics of interest documented. Compared with patients without linked SDOH data, a higher proportion of patients with linked person-level SDOH data were non-Hispanic (NH) White patients (79% vs 71%) and lower proportions were NH Black (10% vs 13%), NH Asian/Pacific Islander (2% vs 4%) and Hispanic patients (2% vs 4%). Patients with linked SDOH were also more likely to have aNSCLC progressed from an earlier stage and received biomarker testing for targetable alterations. Overall, 54% of patients were married, 38% completed a bachelor’s degree or higher, 14% worked in a blue-collar occupation, and 61% had an individual income of ≤$35,000. All 4 of these SDOH characteristics differed significantly by race/ethnicity. Differences in time-to-treatment initiation were statistically significant by marital status (median of 50 [married] vs 55 [not married] days; P=0.02) and individual income (median of 50 [>$60,000] vs 55 [≤$30,000] days; P=0.04). Patients with aNSCLC in these data differed from patients in SEER and ACS estimates with respect to greater representation of patients who are NH White, have lower levels of education, and lower individual income. Conclusions: This analysis demonstrated the feasibility of measuring person-level SDOH using EHR from patients with aNSCLC treated at oncology clinics across the US. RWD with linked SDOH characteristics should be used cautiously to address the representativeness gap in evidence from oncology trials given their potential inherent selection biases.

Evaluation of two-dimensional total bone uptake (2D-TBU) and bone scan index (BSI) extracted from active bone metastatic burden on the bone scintigraphy in patients with radium-223 treatment.

Radium-223 is a first alpha-emitting radionuclide treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with bone metastases. Although the spread-based bone scan index (BSI) and novel index of the intensity-based two-dimensional total bone uptake (2D-TBU) from bone scintigraphy may provide useful input in radium-223 treatment, they have not been evaluated in detail yet. This study aimed to fill this gap by evaluating BSI and 2D-TBU in patients treated with radium-223. Twenty-seven Japanese patients with mCRPC treated with radium-223 were retrospectively analyzed. The patients were evaluated via blood tests and bone scans at baseline and 3 cycles intervals of treatment. BSI and 2D-TBU were analyzed via VSBONE BSI in terms of correlations, response to radium-223 treatment, association with treatment completion, and the Kaplan-Meier survival analysis was performed. Nineteen patients (70.4%) completed six cycles of radium-223 treatment, whereas eight patients (29.6%) did not complete the treatment regimen. A significant difference in baseline BSI and 2D-TBU was observed between these groups of patients. Both BSI and 2D-TBU were highly correlated (r = 0.96, p < 0.001). Univariate analysis showed an association between radium-223 completion in median BSI and 2D-TBU values (p = 0.015) and completion percentage differences (91.7% vs. 45.5%; p = 0.027). The Kaplan-Meier product limit estimator showed that the median overall survival was 25.2 months (95% CI 14.0-33.6 months) in the completion group and 7.5 months (95% CI 3.3-14.2 months) in the without completion group (p < 0.001). The overall survival based on median cutoff levels showed a significant difference in 2D-TBU (p = 0.007), but not in BSI (p = 0.15). The 2D-TBU may offer advantages over BSI in classifying patients towards radium-223 treatment based on the degree of progression of bone metastases. This study supports the importance of preliminary assessment of bone metastasis status using BSI and 2D-TBU extracted from VSBONE BSI for radium-223 treatment decisions.

Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort.

Biliary atresia (BA) is the most common indication for pediatric liver trans plantation, although portoenterostomy is usually performed first. However, due to the high failure rate of portoenterostomy, liver transplantation has been advocated as the primary procedure for patients with BA. It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes. To investigate the effect of prior portoenterostomy in infants un dergoing liver transplantation for BA. This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in Brazil. Patients with BA were divided into two groups: Those under going primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy. Continuous variables were compared using the Student's t-test or the Kruskal-Wallis test, and categorical variables were compared using the χ2 or Fisher's exact test, as appropriate. Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis. Patient and graft survival analyses were conducted with the Kaplan-Meier product-limit estimator, and patient subgroups were compared using the two-sided log-rank test. Forty-two patients were included in the study (25 [60%] girls), 23 undergoing liver transplantation without prior portoenterostomy, and 19 undergoing liver transplantation with prior portoenterostomy. Patients with prior portoenterostomy were older (12 vs 8 months; P = 0.02) at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores (13.2 vs 21.4; P = 0.01). The majority of the patients (35/42, 83%) underwent living-donor liver transplantation. The group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis (39 vs 11%), but this result did not reach statistical significance. Prior portoenterostomy was not a protective factor against portal vein thrombosis in the multivariable analysis after adjusting for age at liver transplantation, graft-to-recipient weight ratio, and use of vascular grafts. Finally, the groups did not significantly differ in terms of post-transplant survival. In our study, prior portoenterostomy did not significantly affect the outcomes of liver transplantation.

Distal Repair After Total Aortic Arch Replacement With Frozen Elephant Trunk in Patients With Chronic Multilevel Thoracic Aortic Disease

To examine the management of distal aortic disease after total arch replacement with the frozen elephant trunk (TAR + FET) in patients with chronic thoracic aortic disease. Two centre retrospective study of consecutive patients treated between January 2010 and December 2019. Primary endpoint was 30 day/in hospital mortality. Secondary end point was mid-term survival. Data are presented as median (IQR). Chi squared or Fisher's exact test was used as appropriate. Estimated survival (standard error) was assessed by the calculating Kaplan-Meier product limit estimator with right censoring of survival data. A p value of < .050 was considered to be statistically significant. STROBE guidelines were followed. A total of 158 patients (72 men; median age 70, IQR 64, 75; median distal aortic diameter 58 mm (46, 68; 127 aneurysmal disease, 31 chronic dissection) underwent TAR + FET. Peri-operative mortality was 10.1% (9/107 elective, 7/51 non-elective). Of 74 (46.8%) patients with a primary distal seal, seven (9.5%) died peri-operatively, distal seal was maintained during follow up in 51, nine underwent late distal repair (two planned, seven unplanned; one open, eight endovascular; one peri-operative death) with a median interval to unplanned repair of 777 days (462, 1480), and seven with loss of seal had no intervention. Distal seal failed in 2/28 (7%) patients with a distal seal length > 30 mm and device oversizing > 10%, compared with 12/39 (31%) patients who did not meet these criteria (p = .031). In 84 patients without primary distal seal, nine (10.7%) died peri-operatively, the distal aorta remained below the size threshold for repair during follow up in 12 patients, 44 had distal repair (median aortic diameter 64 mm, 60, 75; eight open, one hybrid, 35 endovascular repairs; no mortality) at a median of 256 days (135, 740), and 19 did not have distal repair at the end of the follow up period: six died before planned repair at a median interval of 115 days (85, 120); eight were considered unfit; one was assessed as fit but declined; and four patients were awaiting assessment). Median follow up was 46 months (26, 75): no patients were lost to follow up. Estimated ± standard error five year survival was 61.5 ± 4.1%: elective 70.6 ± 4.7%, non-elective 43.2 ± 7.2%. TAR + FET achieved primary distal seal in 47% of patients, but late failure occurred in 21% of patients. Distal repair was ultimately indicated in 84% of survivors without primary distal seal and of these 70% underwent repair, almost 10% died before planned repair, and 13% were considered unfit. Earlier distal endovascular repair and better assessment of patient fitness may improve mid-term outcomes.

Neuroendocrine neoplasms of the ovary: a review of 63 cases

ObjectiveTo describe the clinicopathological characteristics and survival outcomes of ovarian neuroendocrine neoplasms from a curated registry.MethodsThis is a retrospective cross-sectional study of patients in our registry with confirmed ovarian neuroendocrine...

Mental disorders in judicial workers: analysis of sickness absence in a cohort study.

To analyze risk factors for sickness absence due to mental disorders among judicial workers in Bahia, Brazil. Retrospective cohort with follow-up from 2011 to 2016 with 2,660 workers of a judicial sector in Bahia, Brazil. The main outcome measures were survival curves estimated for the independent variables using the Kaplan-Meier product limit estimator and risk factors for the first episode of sickness absence calculated based on the Cox regression model. The survival estimate of the population of this study for the event was 0.90 and from the Cox model the risk factors for the first episode of sickness absence due to mental disorders were: female (HR = 1.81), occupation of magistrate (HR = 1.80), and age over 30 years old (HR = 1.84). In addition, the risk for new cases of sickness absence among women reached 4.0 times the risk for men, in 2015. The estimated relative risks of sickness absence and the observed survival reduction behavior over time add information to the literature on sociodemographic and occupational factors associated with sickness absence due to mental disorders in the public sector. These results highlight the need for further research to more precisely identify vulnerable groups at risk of preventable mental health-related sickness absence in the workplace, better identify the workplace organizational factors that contribute to these disorders as well as studies on the effectiveness of workplace interventions to improve mental health among judicial and other public sectors workers.

Wine international market structure and competitiveness

PurposeThis paper aims to analyse the wine market in relation to international competitiveness and international market structure.Design/methodology/approachTo describe the international market structure, this paper uses Herfindahl–Hirschman Index and Net Export Index to measure export competitiveness revealed symmetric comparative advantage (RSCA). Finally, survival function analyses were developed using the Kaplan–Meier product-limit estimator to characterise the stability and duration of the competitiveness in the international wine market of each country and after they were grouped into Old and New World wine-exporting countries, and Wilcoxon and the Log-rank tests were used to compare the survivor functions.FindingsThe findings have revealed that the import market structure has remained unconcentrated, whereas the export market structure is moderately concentrated. Concerning trade characteristics, France, Italy, Spain, Australia, Chile, New Zealand, Portugal, Argentina, South Africa and Georgia are exporters. Austria is a trader (re-exporter), and the USA, Germany, the UK and the Netherlands are importers with strong domestic consumption. Regarding the RSCA, the New and Old World wine-exporting countries have high scores, specifically France, Italy, Spain, Australia, Chile, New Zealand, Portugal, Argentina, South Africa and Georgia. However, the advantages have weakened for most of the countries analysed. Only a few Old World wine-exporting counties (France, Italy, Spain, Portugal and Georgia) have demonstrated stable comparative advantages over time. However, when grouped into Old World and New World, their survivor functions present little statistical differentiation during the period.Originality/valueThe originality of the paper is that it applies the industrial organisation and comparative advantage approaches to the wine international market, highlighting the top global players. The paper also makes valuable contributions to the wine literature by analysing the duration and stability of comparative advantage in the worldwide wine trade at a country level and comparing them grouped into Old and New World wine-exporting countries.

Disparities in Survival Outcomes among Racial/Ethnic Minorities with Head and Neck Squamous Cell Cancer in the United States

Racial/ethnic (R/E) minorities with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared to White patients. While disparities in patient outcomes for R/E minorities have been well documented, the specific drivers of the inferior outcomes remain poorly understood. This was a population-based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database (NCDB) from 2000-2016. Patient outcomes were stratified by R/E groups including White, Black, Hispanic, Native American/Other, and Asian. The main outcome in this study was overall survival (OS). Univariate time-to-event survival analyses were performed using the Kaplan-Meier product limit estimates and the log-rank test to evaluate the differences between strata. There were 304,138 patients with HNSCC identified in this study, of which 262,762 (86.3%) were White, 32,528 (10.6%) were Black, 6191 were Asian (2.0%), and 2657 were Native American/Other (0.9%). Black R/E minorities were more likely to be uninsured (9% vs. 5%, p < 0.0001), have Medicaid insurance (22% vs. 8%, p < 0.0001), be in a lower income quartile (<30,000, 42% vs. 13%, p < 0.0001), have metastatic disease (5% vs. 2%, p < 0.001), and have a total treatment time 6 days longer than White patients (median 107 vs. 101 days, p < 0.001). The 5-year OS for White, Black, Native American/Other, and Asian patients was 50.8%, 38.6%, 51.1%, and 55.8%, respectively. Among the oropharynx HNSCC patients, the 5-year OS rates in p16+ White, Black, and Asian patients were 65.7%, 39.4%%, and 55%, respectively. After a multivariate analysis, Black race was still associated with an inferior OS (HR:1.09, 95% CI: 1.03-1.15, p = 0.002). This large cohort study of HNSCC patients demonstrates that Black race is independently associated with worse OS, in part due to socioeconomic, clinical, and treatment-related factors.

Disparities in survival outcomes among Black patients with HPV-associated oropharyngeal cancer.

Patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma(HPV-OPSCC) have a favorable prognosis and excellent overall survival (OS), and studies have demonstrated these findings in cohorts of predominantly White patients. Racial/ethnic (R/E) minorities, particularly Black patients, with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared with White patients. In this study, we aimed to determine if Black patients with HPV-OPSCC have a similar favorable prognosis to the White population. This was a population-based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database from 2010 to 2016. We identified patients with Stage I-IV HPV- OPSCC who were treated with radiation, surgery, chemotherapy, or a combination of modalities. Patient outcomes were stratified by R/E groups including White Versus Black patients. The main outcome in this study was OS. Analyses for proportions of categorical variables were performed using a χ2 or Fisher's exact test. Univariate and multivariate time-to-event survival analyses were performed using Kaplan-Meier product limit estimates and log-rank test to test the differences between strata. A Cox proportional hazards regression model was used to assess the association between covariates and risk of death (OS).We identified 9256 OPSCC patients who met inclusion criteria and were treated between 2010 and 2016, of which 7912 were White (85.5%) and 1344 were Black (14.5%). A total of 1727 were HPV-OPSCC, of which 1598 were White (92.5%) and 129 (7.5%) were Black. By race, the 5-year OS for White versus Black OPSCC patients was 42% versus 23%, respectively (log-rank, p < 0.0001). Among HPV-positive OPSCC patients, the 5-year OS for White versus Black patients was 65% versus 39% (log-rank, p < 0.0001). Among HPV-negativepatients, the 5-year OS for White versus Black patients was 36% versus 13% (log-rank, p < 0.0001). On multivariate analysis, after accounting for age, sex, insurance status, income, Charlson-Deyo score, receipt of surgery, distance from facility, and total treatment time, Black race trended toward, but was not associated with worse survival. Hazard ratio(HR:1.24, 95% confidence interval[CI] 0.85-1.81, p = 0.255). This national cohort study of OPSCC patients demonstrates that Black patients with HPV-OPSCC have a poor prognosis and OS similar to HPV-negative White patients. This may be partly due to socioeconomic barriers such as insurance and income. Further work is needed to better understand the specific drivers of inferior survival outcomes in this specific patient population.

Prognostic Value of Translocation 11;14 in Patients with Relapsed/Refractory Myeloma Receiving Anti-CD38 Therapy

Introduction: The translocation t(11;14) is present in ~15% of patients newly diagnosed MM and is associated with a unique clinical and pathological phenotype, despite still being classified as standard risk MM. Ex-vivo studies have also suggested that CD38 expression is decreased in patients with MM that harbors t(11;14), and hence there is a need for real-world data that compares the efficacy of anti-CD38 therapy for patients with and without t(11;14). We used clinical and cytogenetic data from a large, group of real-world patients with relapsed/refractory MM. We hypothesized that CD38 expression would be sufficient in those with t(11;14) to permit activity of anti-CD38 antibodies and that amongst patients receiving anti-CD38 therapies, outcomes would be similar in patients with t(11;14) when compared to those without the translocation. Methods: We conducted a retrospective cohort study using the Flatiron Health electronic health record (EHR)-derived database. We evaluated data from relapsed/refractory MM patients initiating treatment including anti-CD38 therapy in their 2nd or later line of therapy between November 2015 and December 2021. Patients were also required to have documented cytogenetic testing by FISH for high-risk cytogenetic abnormalities (HRCAs) and t(11;14). Presence of t(11;14) and HRCAs defined as deletion 17p, amplification or gain 1q21, t(4;14), t(14;16) and t(14;20) was determined from FISH testing. Our primary outcomes of interest were progression-free survival (PFS) and overall survival (OS). We used the Kaplan-Meier product limit estimator to calculate survivor functions for PFS and OS and compared equality of survivor functions between groups stratified by t(11;14) and HRCA status using log-rank tests. A multivariate analysis was done adjusting for age, sex, functional status, ISS Stage, eGFR and autologous stem cell transplant receipt. Separate analysis was performed for patients with just t(11;14) and no other HRCA, as well as those without (t11;14) and no HRCA (defined as wildtype). Results: An overall cohort of 1,685 patients with MM initiating anti-CD38 therapy as 2nd or later treatment with a median follow up of 22.6 months was identified. Patient characteristics are listed in Table 1. In the overall study sample, patients with and without t(11;14) had a similar median PFS, 16.6 months and 15.0 months respectively (Figure 1, p = 0.24). Median PFS was also similar when comparing patients with t(11;14) and no HRCAs (19.9 months) to wild-type patients (19.6 months) (p = 0.59). Similar associations were observed for these comparisons in OS. Median OS for patients with and without t(11;14) was 49.8 months and 31.9 months respectively (p = 0.07). In multivariable models comparing PFS in patients with t(11;14) to patients without t(11;14), we observed similar risks (HR 1.07, 95% CI 0.80-1.44, p = 0.65) after adjustment for confounders and presence of other HRCAs. When comparing PFS in patients with t(11;14) and no HRCAs to wildtype patients, no statistically significant differences were observed (HR 1.27, 95% CI 0.84-1.94, p = 0.26). In multivariable models comparing OS in patients with t(11;14) to patients without t(11;14), we observed similarly not significant risks (HR 0.82, 95% CI 0.56-1.20, p = 0.31) after adjustment for confounders and presence of other HRCAs. When comparing OS in patients with t(11;14) and no HRCAs to wildtype patients, we also observed similar risks of overall mortality (HR 0.90, 95% CI 0.50-1.61, p = 0.72). Conclusion: In this large real-world study of outcomes of anti-CD38 therapy with relapsed/refractory MM, no significant difference in outcomes were observed between those who had t(11;14) compared to those who did not. This study has important implications as t(11;14) is increasingly recognized as a unique subset of MM with different biology, treatment response rates, and prognosis. As targeted therapies specific to patients with t(11;14) such as venetoclax are increasingly utilized in this patient population, it is important to recognize that anti-CD38 therapy should remain an important part of the treatment landscape for these patients, and that synergistic strategies incorporating bcl-2 inhibition and anti-CD38 targeting should be explored further in clinical trials. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prostate specif c antigen density as a prognostic factor in patients with prostate cancer treated with combined hormonal radiation therapy

Purpose. To evaluate prostate specifc antigen density (PSAD) as a predictor of overall (OS) and cancerspecifc survival (CSS) in patients with prostate cancer (PC) who have undergone combined hormonal-radiation therapy.Material and Methods. In order to assess the prognostic signifcance of PSAD we retrospectively analyzed outcomes of 714 PCa patients who received combined hormonal-radiation therapy at the A.M. Granov Russian Scientifc Center of Radiology and Surgical Technologies, Ministry of Healthcare of Russia, between January 1996 and December 2016. Since the prognosis and management differ according to the extent of tumor involvement, patients were categorized into localized (n=272), locally advanced (n=231) and metastatic (n=211) PC groups. We equentially applied ROC-analysis, Kaplan-Meier product limit estimator and Cox proportional hazards model to assess the prognostic relevance and establish threshold values of PSAD that had a signifcant impact on survival rates.Results. In the localized PC group, PSAD threshold values of 0.34 ng/mL/cc and 0.36 ng/mL/cc were associated with a decrease in OS and CSS, respectively. Patients with “low” PSAD had signifcantly better OS and CSS survival rates in both uni- and multivariate analyses. In locally advanced PC group, PSAD threshold values were 0.28 ng/mL/cc and 0.63 ng/mL/cc for OS and CSS, respectively. However, exceeding the specifed values, in the locally advanced PC group, was not accompanied by a statistically signifcant decrease in survival rates. Finally, in the metastatic PC group, established PSAD threshold values were 2.25 ng/mL/cc and 2.30 ng/mL/ccfor OS and CSS, respectively. According to the results of univariate analysis, patients with “low” PSA tend to demonstrate statistically signifcant better OS and CSS rates. The results of multivariate analysis, however, failed to prove PSAD as an independent prognostic factor within the metastatic PC cohort. Conclusion. PSA density is a reliable tool for assessing survival rates in patients with localized PC who have undergone combined hormonal-radiation therapy.

Behind a cup of coffee: international market structure and competitiveness

PurposeThis study aims to analyse the structure and the competitiveness of the international coffee market.Design/methodology/approachTo describe the international market structure, this study uses Herfindahl–Hirschman index, net export index (NEI), and to measure export competitiveness revealed symmetric comparative advantage (RSCA). Finally, survival function analyses were developed using the Kaplan–Meier product-limit estimator to characterize the stability and duration of the competitiveness in the international coffee market.FindingsThe results reveal that the imports and exports market structure are unconcentrated. NEI shows that several countries are stable in their commercial characteristics (imports, exports and re-exports), nevertheless, NEI also revealed countries transitioning through the commercial characteristics, that the international coffee market structure presents dynamic commercial characteristics. The result for (RSCA shows that Uganda, Ethiopia, Honduras, Brazil, Colombia, Guatemala and Indonesia had the highest values and also resulted in better survival rates along with Italy, India, Mexico and Switzerland. The stability of RSCA indices is investigated by regression analysis, showing a tendency to increase expertise in coffee exports from 2015.Originality/valueThis study provides a comprehensive and recent analysis of the international coffee market structure and competitiveness, contributing to the analysis of the international market of the product.

Maternal lactational investment is higher for sons in chimpanzees

Maternal lactational investment can affect female reproductive rates and offspring survival in mammals and can be biased towards infants of one sex. We compared estimates of lactation effort among mothers, assessed as their potential milk contribution to age-specific infant diets (mother-infant differences in fecal stable nitrogen isotopes, δ15N), to the timing of weaning (infant age at last nursing bout) and to maternal inter-birth interval lengths for male and female infant chimpanzees (Pan troglodytes) at Ngogo, Uganda. Infant males had greater proportions of milk in their age-specific diets, indicated by higher mother-infant differences in δ15N (Generalized Estimating Equation, GEE: p < 0.01). This may mean that mothers of sons showed greater lactation effort than mothers of daughters. Infant males stopped nursing at older ages than infant females (Kaplan–Meier product limit estimate, Breslow estimator: p < 0.05). Mothers of sons showed longer interbirth intervals than mothers of daughters (GEE: p < 0.01). All three measures indicated maternal lactational investment was higher for sons. Male infants may cost mothers more to ensure infant survival than female infants because males are more vulnerable and/or because maternal genetic returns on investment are greater for sons than daughters, as male philopatry means that chimpanzee mothers can have more influence on the reproductive success of sons. Chimpanzee females may trade off growth-related benefits of high lactational investment in male offspring against reduced reproductive rates.Significance statementMaternal investment via lactation affects the reproductive success of female mammals and their offspring and can be biased towards infants of one sex. We investigated lactational variation among wild chimpanzees in relation to infant sex using three proxies for maternal lactational investment: fecal stable nitrogen isotopes, a physiological biomarker that may provide an estimate of lactation effort; observations of nursing, which we used to establish weaning ages; and the lengths of intervals between births of surviving infants. Chimpanzee mothers biased lactational investment toward sons on all three indicators and showed reduced fecundity due to longer inter-birth intervals for mothers of sons than for mothers of daughters. These results would be expected if greater maternal investment toward sons leads to better condition and higher reproductive success for sons later in life, thus to greater inclusive fitness for mothers.

Abstract GS4-05: Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes. A multicenter randomized clinical trial. Sinodar One

Abstract Introduction: Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients. The SLN is the only site of axillary metastasis (MTS) in ≥60% of cases. Recently, a randomized controlled trial (Z0011) comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+ demonstrated no significant statistical difference in relapse and overall survival (OS) rates among the two different groups. However, this study had some limitations: small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (&amp;gt;90%). Given these considerations, the SINODAR-ONE study started in April 2015. Objectives: The aims are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse. Thus evaluating whether SLNB is or is not inferior to ALND. Primary endpoint is OS. Secondary endpoints are disease-free survival (DFS) referring to distant MTS and loco-regional recurrence. Methods: Patients received either mastectomy or conservative surgery plus radiotherapy. They all underwent SLNB and were randomly divided into two arms of treatment: standard (SLNB plus ALND) or experimental treatment (only SLNB). According to multidisciplinary evaluation, patients could undergo additional adjuvant radiotherapy, chemo- and/or hormonal therapy, or no further therapy. Eligibility criteria: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes cN0; no more than 2 macro-metastatic SLNs; no distant MTS; no neo-adjuvant therapy; no previous invasive BC. Exclusion criteria: in situ, inflammatory, contralateral BC; micro-metastatic SLNs; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. All analyses were performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Statistical analysis: OS and DFS were calculated using the Kaplan-Meier Product Limit Estimator and differences between arms were assessed with the log-rank test. Results: The enrollment of patients ended in April 2020 with a total of 889 cases (443: standard arm; 446: experimental arm). In April 2021, we conducted a preliminary analysis on 889 patients. We found the two groups homogeneous for epidemiologic characteristics (age and menopausal status), tumor characteristics (tumor size, pTNM, immunohistochemistry, histology, grading, vascular and lymphatic invasion), and adjuvant therapies. The majority of patients (77.2%) received breast conserving surgery, while 22.8% of patients underwent mastectomy. A median of 2 SLNs were removed in both arms. Overall, only 3 micro-metastatic SNLs were found (1 in the standard arm and 2 in the experimental arm). Conclusion: In sum, OS rate is 99.1% and 99.3% in the standard and experimental arm, respectively; DFS rate is 96.8% and 95.9% in the standard and experimental arm, respectively. After a median follow-up of 36 months, there has been only one axillary recurrence in the experimental arm. Additionally, we found seven distant relapses in both arms; four and three deaths in the standard and experimental arm, respectively. Citation Format: Damiano Gentile, Wolfgang Gatzemeier, Erika Barbieri, Andrea Sagona, Alberto Bottini, Valentina Errico, Alberto Testori, Marta Scorsetti, Giuseppe Canavese, Corrado Tinterri. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes. A multicenter randomized clinical trial. Sinodar One [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-05.

Profiles and Characteristics of Patients with Mild to Moderate COVID -19 Disease Phenotypes in a Teaching Hospital in Kano, Northern Nigeria

Background and Introduction: COVID-19 has affected almost 180 million people around the world, causing the death of about 5 million persons, as of November 16, 2021. The disease presents with a plethora of pulmonary and extrapulmonary symptoms of varying severity. After an exhaustive review of the literature, we found no data on the mild and moderate COVID-19 disease phenotypes in Northern Nigeria. Our objective is to describe the clinical characteristics of non-severe COVID -19 disease phenotypes in Kano State. Methods: This is a retrospective cohort study at the COVID-19 Isolation Center of Muhammad Buhari Specialist Hospital Kano, Nigeria. We included all patients admitted from May 2020 to December 2020. Patients’ medical records were assessed and evaluated to describe the clinical characteristics at presentation. We explored time to discharge between patients aged ≤ 50 years old versus those &gt;50. We applied the Kaplan-Meier product-limit estimator to generate cumulative probabilities of discharge over time and used the Log-rank test to determine differences between the two age groups. We applied Cox Proportional Hazards to identify predictors of time to discharge among the patients in the study. The study variables comprised of time of viral clearance and time to discharge as outcome variables, while main exposure variables included, age, sex, occupation, mode of exposure, presence of co-morbidity, and duration of hospitalization. Results: A total of 187 COVID-19 patients were reviewed. The commonest symptoms were fever, breathing difficulty, and dry cough. There was no recorded death. Contact with a confirmed COVID-19 positive person was the source of infection in 167(89.3%) of patients. We noted faster time to viral clearance in patients on lopinavir compared to those on chloroquine (Log-rank test p-value = 0.048). There were no significant differences in time to discharge between younger (&lt; 50 years) versus older patients (≥ 50 years) [24 days vs. 26 days respectively; Log-rank test p-value = 0.082]. Age, sex, and source of infection did not appear to be predictors of infection phenotype. Conclusion and Implications for Translation: The findings of this study have a bearing on the surveillance and diagnosis of COVID-19 in Nigeria. While the plethora of clinical features may not be limited to infection with the SARS-CoV-2 virus, healthcare practitioners should consider these symptom clusters in addition to cognate contact and travel history when confronted with a suspected COVID-19 infection. Copyright © 2022 Maiyaki et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

Survival outcomes associated with chemotherapy-induced neutropenia in the adjuvant treatment of colorectal cancer with FOLFOX.

81 Background: Patients undergoing adjuvant treatment with FOLFOX for colorectal cancer (CRC) are at risk of developing chemotherapy-induced neutropenia (CIN). We assessed survival outcomes in patients who develop CIN in this setting. Methods: We performed a retrospective chart review of patients with CRC treated with FOLFOX at our institution in Canada from 2013 to 2015. The survival follow-up cut-off date was August 2021. Demographic, treatment, and outcome data were collected. CIN was defined as ANC &lt;1.5, and all episodes of neutropenia were assumed to be the result of chemotherapy. Median OS was calculated using Kaplan-Meier product limit estimates. Results: A total of 302 patients were included (baseline demographics in the table). Median follow-up was 110 months. In the overall cohort, 174 patients (58%) had at least one episode of CIN. CIN occurred in 56% of those with stage II cancer, 43% of those with low risk stage III cancer (T1-3 and N1), and 45% of those with high risk stage III cancer (T4 or N2). Median time to first CIN event was 4.3 months. Among patients with at least one episode of CIN, the first CIN event occurred during the first 3 months of treatment in 110 (63%). Among patients with at least one episode of CIN, 79 (45%) received subsequent granulocyte colony-stimulating factor (GCSF). The median OS in the overall cohort was 171 months. For patients with and without CIN the median OS had not been reached, HR 0.84 (95% CI 0.55-1.29, p=0.43). The median OS for patients with CIN treated with and without GCSF had not been reached, HR 1.02 (95% CI 0.57-1.82, p=0.94). The 5-year survival rate for patients with and without CIN was 87% vs 77%. The 10-year survival rate for patients with and without CIN was 70% vs 64%. A trend toward improved survival in those with CIN remained when results were analyzed by cancer stage. Conclusions: Patients with CIN had a trend toward improved survival compared to those who did not have CIN. There was no indication that GCSF in the setting of CIN impacted survival. The causes for the potentially protective effect of CIN in the setting of adjuvant CRC treatment require further elucidation.[Table: see text]

Northern Bobwhite Survival and Productivity in Relation to Food Supplementation

Northern bobwhite (Colinus virginianus; hereafter, bobwhite) populations have experienced a 3.4% decline annually nation-wide from 1966 to 2018. Limitations on resources, such as food, can regulate population growth. Supplemental food could alleviate resource limitation by raising carrying capacity, leading to increased survival and breeding productivity. Studies have shown higher survival rates and higher nest production when food is supplemented; however, repeating experiments in different contexts allows for strong inference. Our objectives were to assess how supplemental food influenced survival and breeding productivity of resident and translocated bobwhite during a 2-year study on public lands in Leon County, Florida, USA within the Apalachicola National Forest. In accordance with the food limitation hypothesis, we predicted that provisioning of supplemental food would have a positive influence on survival rates and nest productivity. We split the study site into 4 approximately 400-ha zones and randomly assigned 2 treatment (fed) and 2 control (unfed) replicates. Treatment and control zones were flipped during the second field season. Treatments received approximately 1.75 bushels of milo (Sorghum bicolor)/acre 2 times/month year-round via broadcast spreader. We radio-marked 205 bobwhites (102 treatment, 103 control) from February 2019 through October 2020. Individuals were tracked 3–4 times/week for location and survival via radio-telemetry to estimate the breeding season survival and reproduction rates. We estimated survival rates using the Kaplan-Meier product limit estimator. The survival rate during the breeding seasons was higher on average for treatment zones (x̄ = 0.38, standard error [SE] = 0.040) than for control zones (x̄ = 0.29, SE = 0.045). We also observed that 79% of nests found were located in treatment zones compared to 21% in control zones. Our results suggest that food supplementation can improve survival rates and nest production of bobwhite in a food-limited landscape.

Renal Morbidity Following Radical Cystectomy in Patients with Bladder Cancer

BackgroundPatients with chronic kidney disease (CKD) are poor candidates for standard treatments for muscle-invasive bladder cancer (MIBC) and may be more likely to experience adverse outcomes when diagnosed with MIBC. ObjectiveTo investigate factors associated with the development of advanced CKD following radical cystectomy. Design, setting, and participantsUsing national Veterans Health Administration utilization files, we identified 3360 patients who underwent radical cystectomy for MIBC between 2004 and 2018. Outcome measurements and statistical analysisWe examined factors associated with the development of advanced CKD (estimated glomerular filtration rate [eGFR] of <30 ml/min/1.73 m2) after radical cystectomy using multivariable logistic and proportional hazard regression, with and without consideration of competing risks. We examined survival using Kaplan-Meier product limit estimates and proportional hazard regression. Results and limitationsThe median age at surgery was 67 yr and the mean preoperative eGFR was 69.1 ± 20.3 ml/min/1.73 m2. Approximately three out of ten patients (n = 962, 29%) progressed to advanced CKD within 12 mo. Older age (hazard ratio [HR] per 5-yr increase 1.15, 95% confidence interval [CI] 1.10–1.20), preoperative hydronephrosis (HR 1.50, 95% CI 1.29–1.76), adjuvant chemotherapy (HR 1.19, 95% CI 1.00–1.41), higher comorbidity index (HR 1.13, 95% CI 1.11–1.16 per point), and lower baseline kidney function (HR 0.75, 95% CI 0.73–0.78) were associated with the development of advanced CKD. Baseline kidney function at the time of surgery was associated with survival. Generalizability is limited due to the predominantly male cohort. ConclusionsImpaired kidney function at baseline is associated with progression to advanced CKD and mortality after radical cystectomy. Preoperative kidney function should be incorporated into risk stratification algorithms for patients undergoing radical cystectomy. Patient summaryImpaired kidney function at baseline is associated with progression to advanced chronic kidney disease and mortality after radical cystectomy.

Real-world Overall Survival Using Oncology Electronic Health Record Data: Friends of Cancer Research Pilot.

In prior work, Friends of Cancer Research convened multiple data partners to establish standardized definitions for oncology real‐world end points derived from electronic health records (EHRs) and claims data. Here, we assessed the performance of real‐world overall survival (rwOS) from data sets sourced from EHRs by evaluating the ability of the end point to reflect expected differences from a previous randomized controlled trial across five data sources, after applying inclusion/exclusion criteria. The KEYNOTE‐189 clinical trial protocol of platinum doublet chemotherapy (chemotherapy) vs. programmed cell death protein 1 (PD‐1) in combination with platinum doublet chemotherapy (PD‐1 combination) in first‐line nonsquamous metastatic non‐small cell lung cancer guided retrospective cohort selection. The Kaplan‐Meier product limit estimator was used to calculate 12‐month rwOS with 95% confidence intervals (CIs) in each data source. Cox proportional hazards models estimated hazard ratios (HRs) and associated 95% CIs, controlled for prognostic factors. Once the inclusion/exclusion criteria were applied, the five resulting data sets included 155 to 1,501 patients in the chemotherapy cohort and 36 to 405 patients in the PD‐1 combination cohort. Twelve‐month rwOS ranged from 45% to 58% in the chemotherapy cohort and 44% to 68% in the PD‐1 combination cohort. The adjusted HR for death ranged from 0.80 (95% CI: 0.69, 0.93) to 1.15 (95% CI: 0.71, 1.85), controlling for age, gender, performance status, and smoking status. This study yielded insights regarding data capture, including ability of real‐world data to precisely identify patient populations and the impact of criteria on end points. Sensitivity analyses could elucidate data set–specific factors that drive results.

Disease Control After Hypofractionation Versus Conventional Fractionation for Triple Negative Breast Cancer: Comparative Effectiveness in a Large Observational Cohort

Questions remain about whether moderately hypofractionated whole-breast irradiation is appropriate for patients with triple-negative breast cancer. Using the prospective database of a multicenter, collaborative quality improvement consortium, we identified patients with node-negative, triple-negative breast cancer who received whole-breast irradiation with either moderate hypofractionation or conventional fractionation. Using inverse probability of treatment weighting (IPTW), we compared outcomes using the Kaplan-Meier product-limit estimation method with Cox regression models estimating the hazard ratio for time-to-event endpoints between groups. The sample included 538 patients treated at 18 centers in 1 state in the United States, of whom 307 received conventionally fractionated whole-breast irradiation and 231 received moderately hypofractionated whole-breast irradiation. The median follow-up time was 5.0 years (95% confidence interval [CI], 4.77-5.15 years). The 5-year IPTW estimates for freedom from local recurrence were 93.6% (95% CI, 87.8%-96.7%) in the moderate hypofractionation group and 94.4% (95% CI, 90.3%-96.8%) in the conventional fractionation group. The hazard ratio was 1.05 (95% CI, 0.51-2.17; P=.89). The 5-year IPTW estimates for recurrence-free survival were 87.8% (95% CI, 81.0%-92.4%) in the moderate hypofractionation group and 88.4% (95% CI 83.2%-92.1%) in the conventional fractionation group. The hazard ratio was 1.02 (95% CI, 0.62-1.67; P=.95). The 5-year IPTW estimates for overall survival were 96.6% (95% CI, 92.0%-98.5%) in the moderate hypofractionation group and 93.4% (95% CI, 88.7%-96.1%) in the conventional fractionation group. The hazard ratio was 0.65 (95% CI, 0.30-1.42; P=.28). Analysis of outcomes in this large observational cohort of patients with triple-negative, node-negative breast cancer treated with whole-breast irradiation revealed no differences by dose fractionation. This adds evidence to support the use of moderate hypofractionation in patients with triple-negative disease.