Difference In Survival Research Articles

Deep PSA response and extended time‐to‐nadir as robust predictors of survival in Asian patients with de novo metastatic hormone‐sensitive prostate cancer receiving upfront intensified treatment

AbstractIntroductionIn de novo metastatic hormone‐sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real‐world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes.MethodsA prospectively maintained database of consecutive prostate cancer cases in Hong Kong was accessed. Patients diagnosed with de novo mHSPC from 2016 to 2022 and treated with upfront intensification were included in this analysis. Landmark analysis on PSA kinetics at 6‐months following treatment intensification was performed. They were classified based on 1) TTPN (≥6 months vs. <6 months), and 2) a combined response (deep responders achieving both ≥95% PSA decline and TTPN ≥ 6 months vs. shallow responders). Multivariable regression analysis was employed to identify the effects of confounders.FindingsA total of 131 patients were included in this analysis. Classifying patients by combined response best predicted survival outcomes. Deep responders had better progression‐free survival (HR = 0.56; 95%CI = 0.34–0.91; p = 0.019), overall survival (HR = 0.50; 95%CI = 0.26–0.97; p = 0.036), and cancer‐specific survival (HR = 0.43; 95%CI = 0.19–0.99; p = 0.042). Difference in overall survival remained significant after adjustment in multivariable regression analysis.ConclusionOur analysis demonstrates that alternative PSA targets can predict treatment response and survival outcomes in de novo mHSPC patients in a real‐world setting, providing valuable information for patient counselling and potentially guiding future trial design.

Differences in Clinical Outcomes and Survival Among Primary, Secondary, and Concomitant Carcinoma In Situ of the Bladder

Differences in Clinical Outcomes and Survival Among Primary, Secondary, and Concomitant Carcinoma In Situ of the Bladder

Role of vesicoureteral reflux on pediatric kidney allograft function.

Vesicoureteral reflux (VUR) is a common urologic complication of pediatric kidney transplant, though there is little data on the effect of VUR on histologic graft changes or graft survival. All pediatric patients who received a kidney transplant from 2007 to 2020 were selected for retrospective chart review. All participants underwent a voiding cystourethrogram (VCUG) at a 6-month post-transplant. Patients were then categorized into two groups based on vesicoureteral reflux grade: no/low-grade VUR (grades 0-2) and high-grade VUR (grades 3-5). Outcomes collected included graft failure rates, graft function, urinary tract infections(UTIs), proteinuria, and Banff scores at 3- and 12-month post-transplant surveillance kidney biopsies. There were 74 pediatric patients who received a kidney transplant in the designated time-period, and of those 39 had no/low-grade VUR and 35 had high-grade VUR. There was no difference in graft failure among the two groups over time when stratified for age (p = 0.389, CI 0.53-5.08). Patients with high grade VUR had a higher risk of UTI development overall (RR 1.89, 95%CI 1-3.6, p = 0.041), mostly accounted for from increased development of febrile UTI (RR 1.66, 95%CI 1.1-2.6, p = 0.038). Unselected pediatric kidney transplant recipients with high-grade vesicoureteral reflux on VCUG at a 6-month post-kidney transplant are more likely to have febrile UTI compared to those in the low-grade VUR group. There is no difference in graft survival among the two groups.

Can waterfowl buffer the mortality risk induced by GPS tags? A cautionary tale for applied inference across species

GPS tags have become a common tool in ecological studies of animal behaviour and demography despite previous research indicating negative impacts on vital rates across a variety of taxa. Many researchers face tradeoffs when deciding whether they are an appropriate tool because GPS tags may impact vital rates, but they provide detailed data on movements and behaviour that often cannot be obtained in other ways. Using band recovery data, we evaluated the strength of effects induced by GPS tags on annual mortality of adult females across 13 waterfowl taxa, and examined whether taxa with a slower life-history strategy and larger body size were more resilient to GPS tag effects than their fast-lived counterparts with small body size. All species were exposed to hunting, which may interact with underlying processes affecting the impact of GPS tags on mortality, but also allowed for robust analysis of overall annual mortality. Hazard ratios, indicating the risk of death for individuals wearing GPS tags compared to those wearing only metal bands, ranged from 1.13 to 3.25 and the mean proportional difference in survival between marker types across species was 0.33. The magnitude of tag effects was surprisingly consistent across life-history tempo and body size, indicating that slower-lived species did not buffer the effect of wearing GPS tags. Our results highlight that even large, long-lived species, which are generally better at buffering their mortality against environmental adversity, are not immune to the effects GPS tags can have on survival and mortality. The results of our study emphasize the importance of testing for such effects across taxa in future research as technology advances.

Effect of Dietary Short-Chain Fatty Acids on the Immune Status and Disease Resistance of European Seabass Juveniles

(1) Background: This study aimed to evaluate the potential of short-chain fatty acids as functional ingredients to improve the immune status and disease resistance of European seabass (Dicentrarchus labrax) juveniles. (2) Methods: For that purpose, triplicate groups of fish with an initial body weight of 15.2 ± 0.03 g were fed isoproteic (43% crude protein) and isolipidic (18% crude lipids) diets supplemented with sodium acetate (SA), sodium propionate (SP), and sodium butyrate (SB) at two inclusion levels: 0.25% and 0.50%. An unsupplemented diet was used as a control. After 56 days of feeding with the experimental diets, fish were intraperitoneally (i.p.) injected with 100 µL of Vibrio anguillarum (1.2 × 107 Colony Forming Units (CFU)/mL) and mortality was recorded for 3 weeks. At the end of the trial, there were no differences in survival between the treatment groups and the control, but survival was higher in fish fed the diet supplemented with SB 0.50 than SP 0.25 (93.3 vs. 66.7%). Compared to the pre-challenge values, and regardless of diet composition, all hematological parameters (hemoglobin, hematocrit, red blood cells, white blood cells) measured decreased after 4 h of bacterial challenge, except for neutrophils which were increased. Independently of diet composition, lysozyme and nitric oxide decreased at 4 and 24 h post infection. Compared to the control, diets supplemented with SA and SP promoted an up-regulation of both pro- and anti-inflammatory cytokines at 4 h after the challenge, while the diets supplemented with SB promoted an up-regulation of pro- and anti-inflammatory cytokines at 24 h after the challenge. (3) Conclusions: Overall, present results suggest that SA and SP provide a fast response to a bacterial challenge in European sea bass juveniles, while SB provides increased survival.

Worldwide CTEPH Registry: Long-Term Outcomes With Pulmonary Endarterectomy, Balloon Pulmonary Angioplasty, and Medical Therapy.

The European Chronic Thromboembolic Pulmonary Hypertension registry (CTEPH), conducted between 2007 and 2012, reported the major impact of pulmonary endarterectomy (PEA) on the long-term survival of patients with CTEPH. Since then, 2 additional treatments for inoperable CTEPH have become available: balloon pulmonary angioplasty (BPA), and an approved oral drug therapy with the guanylate cyclase stimulator riociguat. The current registry aimed to evaluate the effect of these new therapeutic approaches in a worldwide context. Participation in this international global registry included 34 centers in 20 countries. Between February 2015 and September 2016, 1009 newly diagnosed, consecutive patients were included and followed until September 2019. Overall, 605 patients (60%) underwent PEA and 185 (18%) underwent BPA; 76% of the 219 remaining patients not receiving mechanical intervention (ie, neither PEA nor BPA) were treated with pulmonary hypertension drugs. Oof patients undergoing PEA and BPA, 38% and 78% also received drugs for pulmonary hypertension, respectively. Median age at diagnosis was higher in the BPA and No PEA/BPA groups than in the PEA group: 66 and 69, respectively, versus 60 years. Pulmonary vascular resistance (PVR) was similar in all groups, with an average of 643 dynes/(s·cm-5). During an observation period (>3 years; ≤5.6 years), death was reported in 7%, 11%, and 27% of patients treated by PEA and BPA, and those receiving no mechanical intervention (P<0.001). In Kaplan-Meier analysis, 3-year survival was 94%, 92%, and 71% in the 3 groups, respectively. PEA 3-year survival improved by 5% from that observed between 2007 and 2012. There was no survival difference in patients receiving vitamin K antagonists and non-vitamin K oral anticoagulants (P=0.756). In Cox regression, reduced mortality was associated with: PEA and BPA in the global cohort; history of venous thromboembolism and lower PVR in the PEA group; lower right atrial pressure in the BPA group; and use of pulmonary hypertension drugs, oxygen therapy, and lower right atrial pressure, as well as functional class in the group receiving no mechanical intervention. This second international CTEPH registry reveals important improvement in patient survival since the introduction of BPA and an approved drug for pulmonary hypertension. The type of anticoagulation regimen did not influence survival. URL https://clinicaltrials.gov; Unique identifier: NCT02656238.

Efficacy of Double Valve Replacement/Repair in Patients with Reduced Left Ventricular Ejection Fractions

Introduction: A reduced left ventricular ejection fraction (LVEF) is a known risk factor for double valve replacement or aortic valve replacement in combination with concomitant mitral valve repair (DVR) and is associated with high morbidity and mortality rates. In this study, we sought to analyze the 30-day mortality and long-term survival rates of patients with reduced LVEFs. Methods: A multicenter, retrospective, observational cohort study of patients who underwent DVR was performed at four centers from January 2016 to December 2021. LVEFs were categorized as 41%–50% (n = 120) or ≤40% (n = 58). For the effects of risk factors on 30-day mortality, binary logistic regression was performed. Survival rates were assessed with the Kaplan–Meier method. Results: A total of 178 patients who underwent DVR were included in this study, of whom 67.42% (n = 120) had LVEFs ranging from 41–50% and 32.58% (n = 58) had LVEFs ≤40%. More mechanical valves and tricuspid valve-forming rings were applied in the LVEF ≤40% group (68.97% versus 53.33%, p = 0.047; 31.03% versus 10.83%, p = 0.001). The 30-day mortality rates of DVR patients with LVEFs ranging from 41–50% and ≤40% were 8.33% and 17.24%, respectively (p = 0.078). During the follow-up period, there were no significant differences in long-term survival (log rank p = 0.75). On multivariable logistic regression analysis, age &gt;65 years [odds ratio (OR): 5.559, 95% confidence interval (CI): 1.668–18.524, p = 0.005] and cardiopulmonary bypass (CPB) duration &gt;200 min (OR: 5.031, 95% CI: 1.773–14.277, p = 0.002) were significantly associated with the likelihood of 30-day mortality. Conclusions: Although the differences in 30-day mortality and long-term survival rates between DVR patients with LVEFs ranging from 41–50% and ≤40% were not statistically significant in our cohort, an age &gt;65 years and a CPB duration &gt;200 min were predictors of 30-day mortality.

Evaluating the impact of surgery sequence on infection rates in hip or knee arthroplasty: does sequence matter?

The potential influence of surgical sequence of elective hip-and-knee reconstructive surgery in relation to an infection-related procedure on postoperative infection rates is not clearly understood. Therefore, we aimed to examine the impact of surgical sequence on the incidence of postoperative infections within one-year and the longest available follow-up period in patients undergoing hip-and-knee reconstructive surgery. A case-control study with propensity matching was utilized to examine elective surgeries conducted at Sunnybrook Holland Orthopaedic & Arthritic centre, Toronto, Canada between 2015 and 2018. We determined and categorized them based on their operating room (OR) sequence in relation to an infected case; the cases were those performed right after (post-infection cohort), and the controls were those performed before an infection-related procedure in the same OR (pre-infection cohort). We employed survival analysis to compare the infection incidence within one year and at the longest available follow-up among the propensity-matched cohort. A total of 13,651 cases were identified during the four year period. We successfully matched 153 cases (21 post-infection and 132 pre-infection) using propensity scores. Demographic and clinical characteristics were balanced through matching. Kaplan-Meier survival analysis showed no significant difference in infection-free survival within one year and at a median follow-up of 2.2 years [interquartile range 0.9-5.0] between surgeries conducted before and after infected cases (both log-rank p-values = 0.4). The hazard ratios for infection within one year and the longest follow-up period were both 0.37 [95%Confidence Interval 0.03-4.09, p = 0.418], as no more events occurred after one year. The sequence of surgical procedures, whether or not an elective arthroplasty or lower limb reconstructive procedure occurs before or after an infection-related case in the same OR, does not significantly affect postoperative infection rates. This finding supports the efficacy of the current infection control measures and suggests a reconsideration of surgical scheduling standards.

Racial Differences in Breast Cancer Survival Between Black and White Women According to Tumor Subtype: A Systematic Review and Meta-Analysis.

Despite effective early-detection approaches and innovative treatments, Black women in the United States have higher breast cancer mortality rates compared with White women. The purpose of this systematic review and meta-analysis is to determine the extent of disparities in breast cancer survival between Black and White women according to tumor subtype. A comprehensive database search was performed for full-text, English-language articles published from January 1, 2000, to December 31, 2022. Included studies compared survival between Black and White female patients with breast cancer within subtypes defined by hormone receptor and human epidermal growth factor receptor 2 (HER2)/neu (HER2; now known as ERBB2) status. Random-effects models were used to combine study-specific results and generate pooled relative risks (RRs) and 95% CIs for breast cancer-specific or overall survival (OS). A protocol for this review was registered in PROSPERO (CRD42021268212). Eighteen studies including 228,885 (34,262 Black; 182,466 White) patients with breast cancer were identified. Compared with White women, Black women had a higher risk of breast cancer death for all tumor subtypes. The summary risk of breast cancer death was 50% higher among hormone receptor-positive HER2-negative [HER2-] tumors (RR, 1.50 [95% CI, 1.30 to 1.72]), 34% higher for hormone receptor+/HER2+ (RR, 1.34 [95% CI, 1.10 to 1.64]), 20% higher for hormone receptor-negative (-)/HER2+ (RR, 1.29 [95% CI, 1.00 to 1.43]), and 17% higher among individuals with hormone receptor-/HER2- tumors (hazard ratio, 1.17; 95% CI, 1.10 to 1.25). Black women also had poorer OS than White women for all subtypes. These results suggest there are both subtype-specific and subtype-independent mechanisms that contribute to disparities in breast cancer survival between Black and White women, which require multilevel interventions to address and achieve health equity.

Comparison of outcomes of incremental vs. standard peritoneal dialysis: a systematic review and meta-analysis

BackgroundIncremental peritoneal dialysis (IPD) refers to the use of less than standard full-dose peritoneal dialysis (SPD) in end-stage renal disease patients. While the use of IPD is being reported in the literature, its safety and efficacy vs. SPD is unclear. We hereby performed a systematic review of studies comparing mortality, peritonitis, technique survival, anuria-free survival and residual renal function (RRF) between IPD and SPD.MethodsAll comparative studies published on PubMed, Embase, CENTRAL, Scopus, and Web of Science databases from inception to 5th September 2023 and reporting on given outcomes were eligible.ResultsTen studies were included. Definitions of IPD were heterogenous and hence mostly a qualitative synthesis was undertaken. Majority of studies found no difference in patient survival between IPD and SPD. Meta-analysis of crude mortality data also presented no significant difference. Peritonitis and technique survival were also not significantly different between IPD and SPD in the majority of studies. Data on RRF was conflicting. Some studies showed that IPD was associated with the preservation of RRF while others found no such difference.ConclusionIPD may be a safe alternative to SPD in incident dialysis patients. There seems to be no difference in patient survival, peritonitis, and technique survival between the two modalities. However, the impact of IPD on RRF is still questionable. Evidence is heterogeneous and conflicting to derive firm conclusions.

Abstract A024: ABO blood type and overall survival in patients with pancreatic adenocarcinoma: A systematic review and meta-analysis

Abstract Background/Aim: Recent studies have reported that blood group antigens influence the risk of pancreatic cancer. However, studies on the influence of ABO blood groups on the outcomes of pancreatic cancer have been controversial. Therefore, we aimed to perform a systematic review and meta-analysis to evaluate the association between ABO blood groups and the overall survival in patients with pancreatic adenocarcinoma. Methods: A systematic review of the literature was conducted using the PubMed/Medline, Cochrane Library, and Embase databases in June 2024. This review included observational studies published as complete articles that assessed overall survival or mortality in patients with pancreatic cancer with O blood group compared to non-O. Review Manager 5.1 was used for statistical analysis. Hazard ratios (HRs) with 95% CI were pooled across studies. A random-effects model was used for outcomes with high heterogeneity. In cases where significant heterogeneity was observed (I2 &amp;gt; 40%), sensitivity analyses were conducted. Statistical significance was defined as a p-value &amp;lt; 0.05. Results: Of the 1,624 entries initially identified, nine retrospective studies were included in this meta-analysis, comprising 4,965 individuals. Individuals with O blood type had no statistically significant difference in overall survival compared to the non-O group (HR 1.22; 95% CI 0.97 to 1.53; p = 0.09; I2 = 70%). However, sensitivity analysis revealed one study as the main source of heterogeneity, and its exclusion significantly modified the results favoring the O blood group (HR 1.32; 95% CI 1.13 to 1.54; p = &amp;lt; 0.001; I2 = 10%). Patients with O blood type also had no statistically significant difference in overall survival compared to type A (HR 1.04; 95% CI 0.95 to 1.14; p = 0.43; I2 = 38%) and type B (HR 1.10; 95% CI 0.84 to 1.45; p = 0.49; I2 = 65%). Conclusions: ABO blood groups do not seem to be significantly associated with overall survival and mortality in individuals with pancreatic cancer. However, some analyses revealed significant heterogeneity between the studies. Additionally, a few studies were excluded from the plot because their results were reported in a manner that could not be integrated into a meta-analysis. Further multicenter prospective studies are still needed to validate our results. Citation Format: Tulio L Correa, Marcelo Cristalli, Pedro Luiz Lage Bodour Danielian, Vanio L J Antunes, Matheus Vanzin Fernandes, Natalia Junkes Milioli, Otavio C Martins, Cynthia Florencio de Mesquita, Stefano Baraldo, Bruno Bockorny. ABO blood type and overall survival in patients with pancreatic adenocarcinoma: A systematic review and meta-analysis [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 A024.

Abstract B011: Predictors of survival and cachexia in pancreatic cancer: results from the CAMPP study

Abstract Introduction: Pancreatic Ductal Adenocarcinoma (PDAC) is a major cause of cancer-related death in the US and has an overall 5-year survival rate of only 13%. Cachexia, or cancer associated muscle wasting, is common and negatively affects treatment outcomes and quality of life. Despite these poor outcomes, our understanding of PDAC disease processes and improvements in treatments are limited. Here, we present the first results of the Cancer Associations in MUSC PDAC Patients (CAMPP) study. Methods: This retrospective analysis of 133 surgically resectable PDAC patients at the Medical University of South Carolina (MUSC) between May 2016 to 2021 includes chart review data on survival, treatment, and clinical outcomes. Cancer cachexia was evaluated via total psoas area at the L3 vertebral level, which was standardized by height to produce a Total Psoas Index (TPI). Survival was plotted via unadjusted Kaplan-Meier analysis and TPI and cachexic status was examined for 124 patients with both linear and logistic regressions for unadjusted and adjusted data. Results: When analyzing population survival, we observed a mean overall survival (OS) of 23.6 months and mean progression free survival (PFS) of 17.3 months. Notable survival differences include perioperative vs adjuvant only chemotherapy groups in OS at 2 years (p=0.069) and 5 years (p=0.13). Within the perioperative population, there were differences in PFS (p=0.017) and OS (p=0.056) for patients who responded to therapy at 5 years. To explore potential relationships with cachexia, we performed simple bivariate linear regressions for TPI at diagnosis. We found preliminary associations with sex (p&amp;lt;0.001) and creatinine (p=0.062). When adjusting the model for the confounding effects of race, resection status, and perioperative status, sex (p&amp;lt;0.001) and age (p=0.02) were significantly associated. Importantly, creatinine was not significantly associated (p=0.16). Regardless, an adjusted logistic regression using sex-dependent cachexia cutoffs revealed a clinically relevant odds ratio of 0.9 (95% CI [0.72, 1.09]). This indicates a 10% reduction in the odds of cachexia with every 0.1 mg/dL increase in creatinine, all else held constant. Stratifying with sex-dependent cutoffs for both TPI and creatinine revealed significant differences in 5-year OS (p=0.1) between all four groups. Conclusions: Observing survival trends for patients receiving perioperative care is notable as there are currently no clear guidelines for perioperative chemotherapy despite growing evidence for its efficacy. Further, while sex and age are known predictors of cachexia, creatinine is much less studied. Our associations between creatinine and TPI agree with observations in lung cancer, supporting its use as a clinically relevant marker. Ongoing work is exploring longitudinal measures of cachexia and correlating the CAMPP dataset with tumor genomics to reveal individualized factors impacting patient outcomes. Citation Format: Julie A Disharoon, Arash Velayati, Chloe Matila, Andrew Disharoon, Joseph A Karam, John Redhead, Rachel Burge, Elizabeth G Hill, David T Long, Toros A Dincman. Predictors of survival and cachexia in pancreatic cancer: results from the CAMPP study [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 B011.

Abstract C054: Clinicogenomic determinants of response to FOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line systemic therapy for pancreatic cancer

Abstract Background: FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GA) are two recommended first-line systemic options for pancreatic cancer; however, there is limited evidence to support a particular regimen or provide guidance for treatment selection. We sought to compare outcomes for FFX versus GA across disease stages, and test whether there was an association between clinicogenomic features, treatment response, and survival. Methods: For this retrospective analysis, we utilized AACR’s GENIE PANC v1.2 database, the first large-scale pancreatic cancer dataset that combines genomic data with clinical annotations. The clinicogenomic profiles of patients were stratified and compared by stage: resectable/borderline resectable (R/BR), locally advanced (LA), or metastatic (MET). Patients who received FFX or GA as first-line therapy were compared across stages, with a focus on MET patients. We evaluated OS and PFS as survival outcomes and performed an adjusted analysis using Cox proportional hazards modeling. Treatment responses were further evaluated by change in serum CA 19-9. To test for features associated with treatment response, the genomic profiles of best and worst responders were compared. Results: Of 987 patients with complete genomic data, there were 452 R/BR, 82 LA, and 453 MET. While there was no difference in KRAS status, patients with later-stage disease accumulated greater common co-alterations: CDKN2A (19%, 23%, 35%), SMAD4 (26%, 29%, 30%), TP53 (72%, 73%, 77%), and ARID1A (6%, 6%, 11). Within MET patients, there was no significant difference in PFS between those treated with FFX (n=239) and GA (n=82), but patients treated with FFX had significantly longer OS, even after multivariable adjustment (median 1.14 vs. 0.854 years, p &amp;lt; 0.01; HR: 0.66, 95% CI: 0.49- 0.89, p &amp;lt; 0.01). Despite improved OS in FFX patients, GA patients had a greater reduction in CA 19-9 (median 50.0 vs. 69.0 U/mL). In addition, when comparing the genomic profiles of best/worst responders for MET patients treated with FFX and GA, there was no clear signal that one regimen should be favored over another in a specific context. Exploratory analyses in the R/BR and LA groups indicated no significant survival differences between first-line FFX vs. GA patients, nor in first-line treatment among patients who developed metastases post- diagnosis. Conclusion: Common co-alterations appear to accumulate in later-stage disease, and outcomes in patients undergoing systemic therapy is worse generally in patients with more complex genomic profiles. However, we did not observe any specific genomic features suggestive of a particular response to FFX vs. GA. Of note, we found that Met GA patients had a larger magnitude in CA 19-9 response, even though Met FFX was associated with improved OS. This provokes important questions regarding how biochemical response should be gauged in patients treated with these regimens. Citation Format: Kunling Tong, Elishama Kanu, Ethan Agritelley, Jiayin Bao, Peter J Allen, Daniel P Nussbaum. Clinicogenomic determinants of response to FOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line systemic therapy for 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 C054.

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.

An open-source framework for end-to-end analysis of electronic health record data.

With progressive digitalization of healthcare systems worldwide, large-scale collection of electronic health records (EHRs) has become commonplace. However, an extensible framework for comprehensive exploratory analysis that accounts for data heterogeneity is missing. Here we introduce ehrapy, a modular open-source Python framework designed for exploratory analysis of heterogeneous epidemiology and EHR data. ehrapy incorporates a series of analytical steps, from data extraction and quality control to the generation of low-dimensional representations. Complemented by rich statistical modules, ehrapy facilitates associating patients with disease states, differential comparison between patient clusters, survival analysis, trajectory inference, causal inference and more. Leveraging ontologies, ehrapy further enables data sharing and training EHR deep learning models, paving the way for foundational models in biomedical research. We demonstrate ehrapy's features in six distinct examples. We applied ehrapy to stratify patients affected by unspecified pneumonia into finer-grained phenotypes. Furthermore, we reveal biomarkers for significant differences in survival among these groups. Additionally, we quantify medication-class effects of pneumonia medications on length of stay. We further leveraged ehrapy to analyze cardiovascular risks across different data modalities. We reconstructed disease state trajectories in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on imaging data. Finally, we conducted a case study to demonstrate how ehrapy can detect and mitigate biases in EHR data. ehrapy, thus, provides a framework that we envision will standardize analysis pipelines on EHR data and serve as a cornerstone for the community.

Management of Ipsilateral Breast Tumor Recurrence Following Breast Conservation Surgery for Ductal Carcinoma In Situ: A Data-Poor Zone.

Breast conserving surgery (BCS) is well established for the management of ductal carcinoma in situ (DCIS), but neither randomized trials nor guidelines address management of ipsilateral breast tumor recurrence (IBTR) after BCS for DCIS. We identified women treated with BCS for DCIS who developed IBTR as a first event. Between those treated with mastectomy versus re-BCS, we compare the clinicopathologic characteristics, the use of adjuvant radiotherapy (RT) both upfront ("primary RT") and post IBTR ("secondary RT"), of tamoxifen, the rate of third events (local, regional, distant), and both breast cancer specific (BCSS) and overall survival (OS). Of 3001 women treated with BCS for DCIS (1978-2010), 383 developed an IBTR as a first event (1983-2023) and were treated by mastectomy (51%) versus re-BCS (49%). Compared with re-BCS, mastectomy patients at initial treatment were higher grade (74% versus 59%, p = 0.004), with more frequent primary RT (61% versus 21%, p < 0.001). Third local events were more frequent for re-BCS than mastectomy (16% versus 3%, p = 0.001), but there were no differences in breast cancer specific or overall survival. For isolated IBTR following BCS for DCIS and treated by mastectomy versus re-BCS (1) mastectomy was associated with less favorable initial pathology and more frequent use of primary RT, (2) re- recurrence was more frequent with re-BCS, and (3) BCSS and OS were comparable. Our data suggest a wider role for re-BCS and further study of the relationship between secondary RT and the rate of third breast events.

Effects of feeding a negative dietary cation and anion difference diet to twin-bearing Merino ewes in late gestation on parturition outcomes.

In Australia, dystocia is responsible for 53% of lamb mortalities, and calcium deficiencies may be a contributing factor. A negative dietary cation anion difference (DCAD) diet can increase calcium concentrations in sheep. Therefore, this study aimed to investigate the effects of a negative DCAD diet on metabolic state, mineral status and parturition duration in ewes compared with those fed a positive DCAD diet. At approximately day 130 of gestation (dG), 71 twin-bearing ewes were placed in the following treatment groups; ewes receiving a positive DCAD TMR (total mixed ration) (DCAD of total diet = 281.8 mEq/kg DM; n = 35) and twin-bearing ewes receiving a negative DCAD TMR (DCAD of total diet = -89.0 mEq/kg DM; n = 36). Urine and blood were sampled on dG 130, 140, and 145, and blood was also sampled at the onset of parturition and 4h post-partum. Urine was analysed for pH and blood was analysed for metabolites, mineral concentration and acid-base balance. Lamb liveweight, rectal temperature, blood glucose and lactate, and body morphology were measured. Serum phosphate concentrations at dG 145 were significantly lower for negative DCAD ewes compared with positive DCAD ewes (1.9 ± 0.1 versus 2.1 ± 0.1 mmol/L, P = 0.047). Ionised calcium (P = 0.09) and serum magnesium (P = 0.09) pre-partum were marginally greater in the negative DCAD ewes (1.35 ± 0.06 and 1.06 ± 0.03 mmol/L respectively) compared with the positive DCAD ewes (1.18 ± 0.08 and 0.98 ± 0.04 mmol/L respectively). Urine pH was lower in the negative DCAD ewes compared with positive DCAD ewes at both dG 140 (7.38 ± 0.17 versus and 8.10 ± 0.19. P = 0.01) and dG 145 (and 7.20 ± 0.19 versus 8.25. P < 0.01). The birth interval between the first the second-born lamb was shorter in the negative DCAD ewes compared with the positive DCAD ewes (P = 0.02), but no differences in lamb survival or lamb viability (P > 0.05) were seen. The negative DCAD diet reduced parturition duration, most likely due to the marginally greater ionised calcium and magnesium concentrations. Despite this improvement, the negate DCAD ewes did not reach urinary acidification, indicating that the marginally significant greater ionised calcium and serum magnesium concentrations was due to the magnesium in the diets and not metabolic acidosis. Further research testing a negative DCAD diet that can achieve the target urine pH is required to determine whether this diet can decrease parturition duration and improve lamb viability.

Survival associated with the use of sentinel lymph node in addition to lymphadenectomy in early-stage cervical cancer treated with surgery alone: A sub-analysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study

AimThe aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer. MethodsInternational, multicenter, retrospective study. Inclusion criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy (‘SLN’ group) or pelvic lymphadenectomy alone (‘non-SLN’ group). Results1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5–98.5 versus 92.0 %,95 %CI:90.0–94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8–99.9 versus 96.8 %,95 %CI:95.4–98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266–0.959, p = 0.037 and HR:2.703,95 %CI:1.389–5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039). ConclusionAdding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer.

Long-term Survival in Esophageal Cancer: Comparison of Minimally Invasive and Open Esophagectomy

Thoracoscopic esophagectomy is a less invasive surgical procedure; however, evidence of its effect on long-term survival is limited. We evaluated long-term survival after the procedure in patients with esophageal carcinoma. This retrospective multicenter study involved 1,559 consecutive patients with esophageal carcinoma who underwent thoracoscopic esophagectomy or open esophagectomy between 2012 and 2019 at two Japanese high-volume cancer centers. Propensity score matching analysis was performed to compare short- and long-term outcomes. Additionally, stage-specific survival rates were compared between the two groups. Three-hundred-and-thirteen patients were matched and analyzed. The 1-, 3-, and 5-year overall survival rates were 84.5%, 60.5%, and 52.1%, respectively, in the matched open esophagectomy group; and 87.2%, 68.6%, and 61.8%, respectively, in the matched thoracoscopic esophagectomy group. The weighted Cox regression model showed significantly better survival in the thoracoscopic esophagectomy group than in the open esophagectomy group (hazard ratio = 0.74, 95% confidence interval: 0.582-0.941). Deaths from other causes occurred more frequently in the open esophagectomy group than in the thoracoscopic esophagectomy group. Stratified analysis showed no significant survival differences between the cStage I or II and pStage 0 or I subgroups. However, the thoracoscopic esophagectomy groups with cStage III or IV and pStage II, III, or IV had significantly better overall survival. This study demonstrated the survival benefits of thoracoscopic esophagectomy particularly for highly advanced esophageal carcinoma.

Unveiling the mysteries of HER2-low expression in breast cancer: pathological response, prognosis, and expression level alterations

BackgroundThe novel anti-HER2 antibody drug conjugates (ADCs) can effectively improve the long-term survival of patients with HER2-low expression breast cancer. However, pathological responses to neoadjuvant therapy (NAT) within HER2-low expression breast cancer, the relationship between pathological response and prognosis and the transformation of HER2 status are all now poorly understood.MethodsThe patients with HER2-0 and HER2-low expression breast cancer receiving NAT at Harbin Medical University Cancer Hospital between Jan. 2014 and Nov. 2018 were retrospectively explored. HER2 low expression refers to the IHC 1 + or 2 + and FISH negative. The Kappa test was utilized for analyzing the consistency rate of HER2 expression. To evaluate disease-free survival (DFS) and overall survival (OS), this research employed both the Kaplan-Meier analysis and the Cox regression.ResultsIn this study, 178 patients with HER2-0 and 344 patients with HER2-low expression breast cancer were included. In comparison with the HER2-0 group, it is shown that patients in the HER2-low group have more possibility to be younger compared to those 50 years old (P < 0.014), have more premenopausal patients (P < 0.001), a higher proportion of hormone receptor (HR) positive patients (P < 0.001), and less proportion of stage III V patients (P < 0.034). When NAT was finished, the pCR rate became 23.6% in the HER2-0 group while 22.1% in the HER2-low group, and there was also a higher pCR rate in HR- patients in comparison with that in HR + patients (P < 0.01). Considering HER2 expression inconsistency, the overall HER2 inconsistency rate was 30.4% (Kappa = 0.431, P < 0.01). Among patients initially diagnosed as HER2-0, 34% (N = 61) were re-diagnosed as HER2-low after NAT. After stratification by HR expression status, HR+/HER2-0 patients transformed to HER2-low after NAT in 37%, and 32% of HR- patients changed from HER2-0 to HER2-low. In this survival analysis, there were both better DFS rates (P = 0.009) and OS rates (P = 0.026) in the HR-/HER2-low patients in comparison with the HR-/HER2-0 patients, while the HER2-0 and HER2-low patients in the HR + group had no significant survival difference. Additionally, for non-pCR patients, there was better DFS (P = 0.029) and OS (P = 0.038) in the HER2-low group in comparison with that of the HER2-0 group, while no significant survival difference exists between pCR patients.ConclusionAfter HR stratification, there are unique clinical characteristics and prognostic outcomes in HER2-low expression breast cancer, which indicates the potential to become a specific molecular subtype of breast cancer. The significant instability of HER2-low expression status between primary tumor and residual invasive disease suggests that multiple detections of HER2 status should be emphasized in NAT strategies.