Multi-institutional Study Research Articles

Retrospective evaluation of the prevalence and risk factors associated with red blood cell transfusions in cats with urethral obstruction (2009-2019): 575 cases.

To evaluate the prevalence of red blood cell (RBC) transfusions and factors associated with the need for transfusion in cases of feline urethral obstruction (FUO). Secondarily, to compare survival to discharge in cats receiving an RBC transfusion versus those that did not. Retrospective, multi-institutional study from 2009 to 2019. Four university teaching hospitals. Six hundred twenty-two total occurrences of FUO in 575 cats. None. Medical records were retrospectively reviewed for pertinent information. The overall prevalence of severe anemia (PCV<0.20L/L [<20%]) at presentation was 1.0% (6/622). The prevalence of RBC transfusions during hospitalization was 2.1% (13/622). Cats that received an RBC transfusion weighed significantly less than those that did not (4.9 vs 5.8kg; P=0.034) and had a lower PCV at presentation (0.30L/L [30%] vs 0.41L/L [41%]; P<0.001). Hospitalization time (240 vs 72h) and indwelling urinary catheter time (168 vs 48h) were significantly longer in cats receiving a transfusion compared with those that did not (P<0.001). Creatinine concentrations were not significantly associated with transfusion administration, while BUN was higher in cats receiving a transfusion (15.35mmol/L [43mg/dL] vs. 11.78mmol/L [33mg/dL]; P=0.043). Transfusion rates were significantly higher in cats undergoing perineal urethrostomy (5.5%) compared with those that did not undergo surgery (0.97%; P<0.001). The overall survival to discharge rate was 96%. Cats not receiving an RBC transfusion were significantly more likely to survive to discharge than those that did (odds ratio: 14.7, 95% confidence interval: 1.8-37; P<0.001). FUO is rarely associated with severe anemia and the need for RBC transfusions. In this study, cats receiving an RBC transfusion were less likely to survive to discharge; therefore, requiring a blood transfusion may be associated with a worse prognosis. In addition, the need for surgical intervention was associated with a higher prevalence of RBC transfusions.

Prognostic nomogram to predict cancer-specific survival with small-cell carcinoma of the prostate: a multi-institutional study

ObjectiveThe aim of this study is to examine the predictive factors for cancer-specific survival (CSS) in patients diagnosed with Small-Cell Carcinoma of the Prostate (SCCP) and to construct a prognostic model.MethodsCases were selected using the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method was utilized to calculate survival rates, while Lasso and Cox regression were employed to analyze prognostic factors. An independent prognostic factor-based nomogram was created to forecast CSS at 12 and 24 months. The model’s predictive efficacy was assessed using the consistency index (C-index), calibration curve, and decision curve analysis (DCA) in separate tests.ResultsFollowing the analysis of Cox and Lasso regression, age, race, Summary stage, and chemotherapy were determined to be significant risk factors (P &amp;lt; 0.05). In the group of participants who received training, the rate of 12-month CSS was 44.6%, the rate of 24-month CSS was 25.5%, and the median time for CSS was 10.5 months. The C-index for the training cohort was 0.7688 ± 0.024. As for the validation cohort, it was 0.661 ± 0.041. According to the nomogram, CSS was accurately predicted and demonstrated consistent and satisfactory predictive performance at both 12 months (87.3% compared to 71.2%) and 24 months (80.4% compared to 71.7%). As shown in the external validation calibration plot, the AUC for 12- and 24-month is 64.6% vs. 56.9% and 87.0% vs. 70.7%, respectively. Based on the calibration plot of the CSS nomogram at both the 12-month and 24-month marks, it can be observed that both the actual values and the nomogram predictions indicate a predominantly stable CSS. When compared to the AJCC staging system, DCA demonstrated a higher level of accuracy in predicting CSS through the use of a nomogram.ConclusionClinical prognostic factors can be utilized with nomograms to forecast CSS in Small-Cell Carcinoma of the Prostate (SCCP).

Chronic Health Conditions and Longitudinal Employment in Survivors of Childhood Cancer

Employment is an important factor in quality of life and provides social and economic support. Longitudinal data on employment and associations with chronic health conditions for adult survivors of childhood cancer are lacking. To evaluate longitudinal trends in employment among survivors of childhood cancer. Retrospective cohort study of 5-year cancer survivors diagnosed at age 20 years or younger between 1970 and 1986 enrolled in the multi-institutional Childhood Cancer Survivor Study (CCSS). Sex-stratified employment status at baseline (2002 to 2004) and follow-up (2014 to 2016) was compared with general population rates from the Behavioral Risk Factor Surveillance System cohort. Data were analyzed from July 2021 to June 2022. Cancer therapy and preexisting and newly developed chronic health conditions. Standardized prevalence ratios of employment (full-time or part-time, health-related unemployment, unemployed, not in labor force) among adult (aged ≥25 years) survivors between baseline and follow-up compared with the general population. Longitudinal assessment of negative employment transitions (full-time to part-time or unemployed at follow-up). Female participants (3076 participants at baseline; 2852 at follow-up) were a median (range) age of 33 (25-53) years at baseline and 42 (27-65) years at follow-up; male participants (3196 participants at baseline; 2557 at follow-up) were 33 (25-54) and 43 (28-64) years, respectively. The prevalence of full-time or part-time employment at baseline and follow-up was 2215 of 3076 (71.3%) and 1933 of 2852 (64.8%) for female participants and 2753 of 3196 (85.3%) and 2079 of 2557 (77.3%) for male participants, respectively, with declining standardized prevalence ratios over time (female participant baseline, 1.01; 95% CI, 0.98-1.03; follow-up, 0.94; 95% CI, 0.90-0.98; P < .001; male participant baseline, 0.96; 95% CI, 0.94-0.97; follow-up, 0.92; 95% CI, 0.89-0.95; P = .02). While the prevalence of health-related unemployment increased (female participants, 11.6% to 17.2%; male participants, 8.1% to 17.1%), the standardized prevalence ratio remained higher than the general population and declined over time (female participant baseline, 3.78; 95% CI, 3.37-4.23; follow-up, 2.23; 95% CI, 1.97-2.51; P < .001; male participant baseline, 3.12; 95% CI, 2.71-3.60; follow-up, 2.61; 95% CI, 2.24-3.03; P = .002). Among survivors employed full-time at baseline (1488 female participants; 1933 male participants), 285 female participants (19.2%) and 248 male participants (12.8%) experienced a negative employment transition (median [range] follow-up, 11.5 [9.4-13.8] years). Higher numbers and grades of chronic health conditions were significantly associated with these transitions. In this retrospective analysis of adult survivors of childhood cancer, significant declines in employment and increases in health-related unemployment among cancer survivors compared with the general population were identified. A substantial portion of survivors in the midcareer age range fell out of the workforce. Awareness among clinicians, caregivers, and employers may facilitate clinical counseling and occupational provisions for supportive work accommodations.

Implementation of a geriatric assessment SmartPhrase: A multi-institutional pilot study.

Implementation of a geriatric assessment SmartPhrase: A multi-institutional pilot study.

High risk features in colorectal adenomatous polyps: A multi-institutional study

High risk features in colorectal adenomatous polyps include size >1 cm and advanced histology: high-grade dysplasia and villous architecture. We investigated whether the diagnostic rates of advanced histology in colorectal adenomatous polyps were similar among institutions across the United States, and if not, could differences be explained by patient age, polyp size, and/or CRC rate. Nine academic institutions contributed data from three pathologists who had signed out at least 100 colorectal adenomatous polyps each from 2018 to 2019 taken from patients undergoing screening colonoscopy. For each case, we recorded patient age and sex, polyp size and location, concurrent CRC, and presence or absence of HGD and villous features. A total of 2700 polyps from 1886 patients (mean age: 61 years) were collected. One hundred twenty-four (5 %) of the 2700 polyps had advanced histology, including 35 (1 %) with HGD and 101 (4 %) with villous features. The diagnostic rate of advanced histology varied by institution from 1.7 % to 9.3 % (median: 4.3 %, standard deviation [SD]: 2.5 %). The rate of HGD ranged from 0 % to 3.3 % (median: 1 %, SD: 1.2 %), while the rate of villous architecture varied from 1 % to 8 % (median: 3.7 %, SD: 2.5 %). In a multivariate analysis, the factor most strongly associated with advanced histology was polyp size >1 cm with an odds ratio (OR) of 31.82 (95 % confidence interval [CI]: 20.52–50.25, p < 0.05). Inter-institutional differences in the rate of polyps >1 cm likely explain some of the diagnostic variance, but pathologic subjectivity may be another contributing factor.

How far are we off? Analyzing the accuracy of surgical margin relocation in the head and neck.

Positive surgical margin rates remain high in head and neck cancer surgery. Relocation is challenging given the complex, three-dimensional (3D) anatomy. Prospective, multi-institutional study to determine accuracy of head and neck surgeons and pathologists relocating margins on virtual 3D specimen models using written descriptions from pathology reports. Using 3D models of 10 head and neck surgical specimens, each participant relocated 20 mucosal margins (10 perpendicular, 10 shave). A total of 32 participants, 23 surgeons and 9 pathologists, marked 640 margins. Of the 320 marked perpendicular margins, 49.7% were greater than 1 centimeter from the true margin with a mean relocation error of 10.2 mm. Marked shave margins overlapped with the true margin a mean 54% of the time, with no overlap in 44 of 320 (13.8%) shave margins. Surgical margin relocation is imprecise and challenging even for experienced surgeons and pathologists. New communication technologies are needed.

Association between consumption of small fish and all-cause mortality among Japanese: the Japan Multi-Institutional Collaborative Cohort Study.

Although small fish are an important source of micronutrients, the relationship between their intake and mortality remains unclear. This study aimed to clarify the association between intake of small fish and all-cause and cause-specific mortality. We used the data from a cohort study in Japan. The frequency of the intake of small fish was assessed using a validated food frequency questionnaire. The hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality according to the frequency of the intake of small fish by sex were estimated using a Cox proportional hazard model with adjustments for covariates. The Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. A total of 80,802 participants (34,555 males and 46,247 females), aged 35-69 years. During a mean follow-up of 9.0 years, we identified 2,482 deaths including 1,495 cancer-related deaths. The intake of small fish was statistically significantly and inversely associated with the risk of all-cause and cancer mortality in females. The multivariable-adjusted HRs (95% CIs) in females for all-cause mortality according to the intake were 0.68 (0.55-0.85) for intakes 1-3 times/month, 0.72 (0.57-0.90) for 1-2 times/week, and 0.69 (0.54-0.88) for ≥3 times/week, compared with the rare intake. The corresponding HRs (95% CIs) in females for cancer mortality were 0.72 (0.54-0.96), 0.71 (0.53-0.96), and 0.64 (0.46-0.89), respectively. No statistically significant association was observed in males. Intake of small fish may reduce the risk of all-cause and cancer mortality in Japanese females.

Abstract PO3-05-13: A Multi-Institutional Review of Contralateral Axillary Metastases: Time for Reclassification as Local-Regional Event?

Abstract Background Current American Joint Committee on Cancer (AJCC) breast cancer staging considers contralateral axillary metastasis (CAM) stage IV disease (M1). Retrospective studies suggest that women with CAM have improved overall survival (OS) compared to those with distant metastasis (M1) and/or comparable OS to locally advanced breast cancer (LABC). These studies support consideration of curative intent treatment; however, they contain heterogeneous cohorts with highly variable treatment strategies. We sought to evaluate treatment and outcomes in a well-defined CAM cohort treated with contemporary systemic and locoregional therapy. Methods We performed a retrospective multi-institution cohort study to compare OS of patients with CAM matched 1:3 on age +/- 5 years to LABC (defined as cN2-3 and/or pN2-3), and to non-CAM M1. CAM patients classified as type 1) de novo CAM, synchronous with the contralateral primary, 2) metachronous isolated CAM in the setting of prior surgical and/or radiation treatment to primary index cancer, 3) synchronous with, or 4) metachronous after an in-breast or axillary nodal recurrence of the primary index cancer. The M1 cohort included de novo and recurrent metastasis with varied sites and number of metastasis. OS was defined as time from CAM diagnosis to death or last follow-up for CAM patients; time from primary diagnosis to death or last follow-up for LABC; and time from metastatic diagnosis to death or last follow-up for M1. Unadjusted OS was estimated with the Kaplan-Meier method, and Cox proportional hazards models were used to estimate the association of group with OS after adjustment for covariates Results We identified 57 CAM and 155 LABC from 8 institutions (2016-2022), and 632 M1 from a single institution. The median age was similar between groups (CAM=59 years, LABC=58, M1=57, p=0.44), and there were no statistically significant differences in hormone receptor status (p=0.25). There were more Non-Hispanic Black patients in the M1 cohort compared to CAM or LABC (p&amp;lt; 0.001). The majority of CAM cases were delayed metachronous from the index cancer (type 2, 35.1%), or synchronous with a recurrence (type 3, 33.3%). Type 1 (de novo, 14%) and type 4 (delayed metachronous after breast cancer recurrence, 17.5%) were less frequent. Among CAM patients, 49.1% were hormone receptor positive (HR+)/HER2-negative (HER2-), 22.8% HR-/HER2-, 10.5% HR+/HER2+, and 5.3% HR-/HER2+. Comparing CAM versus LABC, invasive ductal carcinoma (IDC) was more commonly seen in CAM (82.5% vs 66.5%), as was grade 3 (45.6% vs 35.5%), and triple negative (22.8% vs 13.5%). Conversely, in LABC, treatment of the primary index cancer more frequently included chemotherapy (CAM=71.9%, LABC=92.3%), mastectomy (CAM=54.4%, LABC 74.2%), and adjuvant radiation (CAM=73.7%, LABC=90.3%). On multivariable analysis adjusting for age, race/ethnicity, and hormone receptor status, both CAM and M1 had inferior survival to LABC (Table 1), but with a 2.4-fold difference for CAM (95% CI 1.42-4.07, p=0.001) versus a 6.3-fold difference for M1 (95% CI 4.29-9.23, p=&amp;lt; 0.001). Discussion In this contemporary, multi-institution study, we demonstrated that CAM patients selected for presumed curative intent treatment experienced improved OS when compared to stage IV (M1) patients. Our data adds additional support for re-evaluating the current stage IV designation, in favor of N3, and consideration of curative intent treatment in this disease. Table. Adjusted* Overall Survival Comparing Patients with Breast Cancer Contralateral Axillary Metastasis (CAM) to those with Locally Advanced Breast Cancer (LABC) and Metastatic Disease (M1) *Adjusted for age, race/ethnicity, hormone receptors. Citation Format: Meghan R. Flanagan, Stephanie Downs-Canner, Samantha Thomas, Astrid Botty van de bruele, Margaret Lillie, Kristalyn Gallagher, Tammeza Gibson, James Jakub, Alexandra Verosky, Sarah Tevis, Malia Brennan, Francys Verdial, Jennifer Q. Zhang, Leisha Elmore, Jennifer Plichta, Laura Rosenberger. A Multi-Institutional Review of Contralateral Axillary Metastases: Time for Reclassification as Local-Regional Event? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-13.

Abstract PO3-06-10: Real World Outcomes with Sacituzumab Govitecan in Metastatic Triple Negative Breast Cancer Patients: A Multi-Institution Study

Abstract Background Sacituzumab govitecan (SG) is approved for treatment of metastatic triple negative breast cancer (mTNBC) in the second line and beyond. Little is known about the real-world outcomes of SG. We aim to evaluate the real-world effectiveness and toxicity outcomes of SG in heterogenous heavily pretreated mTNBC patients (pts) to investigate the consistency of the outcomes in comparison to the clinical trial population. Methods A multi-center retrospective study of pts with mTNBC treated with SG in the US from January 2021 until May 2023 was conducted. Demographics and clinicopathological variables including site of metastases, prior lines of therapy, relative dose intensity (RDI), adverse events (AEs), HER2 immunohistochemistry (IHC) score at time of metastasis, clinical response, clinical benefit rate (CBR) defined as (complete response, partial response (PR) or stable disease (SD) &amp;gt; 6 months) and last follow-up were collected. For continuous variables, Mann-U Whitney and Kruskal Wallis tests were used to compare mean, median, standard deviation, and range. For categorical variables, Fisher's exact tests and Pearson Chi-square tests were used. Univariate and multivariate cox regression models examined RDI and survival outcomes. SAS v9.4 was used to perform statistical analysis at a significance level of 0.05. Results A total of 111 pts were analyzed. The median age was 58 years (range 29-84). The majority of pts were heavily pretreated: 59.1% received &amp;gt;3 prior lines of treatment (Tx) in the metastatic setting, 54.1% received prior immune checkpoint inhibitor (ICI), 8.1% received prior olaparib. 55% of pts had significant disease burden defined by &amp;gt;=3 organs involved by metastatic disease, with 22.5% having brain metastasis at the time of initiation of SG. Of note, 51% had primary refractory disease defined as relapse within 12 months of completion of adjuvant chemotherapy. 98.1% experienced any grade AEs, with the most common being anemia 63.1%. Grade 3 AEs occurred in 51.4% pts with neutropenia being the highest 32.4% followed by anemia 14.4%, diarrhea 7.2% and fatigue 7.2%. Tx interruptions and dose reductions due to AEs occurred in 52.3% of patients and Tx discontinuation rate due to AEs was 11.8%. Elderly pts (defined as &amp;gt;65 years) did not have higher rates of dose reductions due to AEs compared to young pts (&amp;lt; = 65 years) (37.8% vs 59.7 %), p=0.043). The median RDI is 92% (interquartile range (IQR) 33%-100%). The median RDI in elderly pts was 94% (IQR 50%-100%). Among pts in which response was assessed, objective response rate (ORR) was 26.6% (25 pts had PR), and 38.3% had SD. Interestingly, the rate of alopecia was higher in pts who had PR as the best response (28%), compared to 5.6% in pts who had SD, and 3% in progressive disease (PD) p=0.004. The median prior line of therapy in pts who had PR and SD as best response was 2 (IQR 1, 5) (IQR1, 12), respectively, compared to a median of 3 (IQR 1, 7) in pts with PD, p&amp;lt; 0.001. The CBR was 49% (46/94). The median duration of clinical benefit was 7 months IQR (2, 16) with median overall survival of 13 months IQR (2.5, 39) compared to 5.7 months IQR (0.03, 27) in pts without clinical benefit (p&amp;lt; 0.001). 56.9% (62/109) of pts had HER2 low disease and the clinical benefit rate in this subgroup was 14.3% (23/62). Conclusion: In a heavily pretreated cohort, SG retains clinical activity and tolerability in mTNBC. This is reassuring given pts on clinical trials tend to be healthier compared to real-world clinical practice. Citation Format: Sabah Alaklabi, Arya Mariam Roy, Paola Zagami, Nicole Held, Saba Shaikh, Lubna Chaudhary, Yara Abdou, Shipra Gandhi. Real World Outcomes with Sacituzumab Govitecan in Metastatic Triple Negative Breast Cancer Patients: A Multi-Institution Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-10.

Abstract PS08-03: Sequencing Antibody-Drug Conjugate after Antibody-Drug Conjugate in Metastatic Breast Cancer (A3 study): Multi-Institution Experience and Biomarker Analysis

Abstract Background: Antibody-drug conjugates (ADCs) improve survival in patients with metastatic breast cancer (MBC) and offer the potential for targeted delivery of highly potent therapy. Many patients are now candidates for multiple ADCs, but optimal strategies for sequencing are unknown. We previously reported on a single institution experience of patients receiving multiple ADCs for MBC (Abelman, ASCO 2023). Here we report a multi-institution update with biomarker analysis. Methods: We included all patients treated at three academic medical institutions who received multiple ADCs for MBC. Patients were included if they had hormone receptor positive, HER2-negative (HR+/HER2-) breast cancer or triple-negative breast cancer (TNBC); patients with HER2+ metastatic breast cancer were excluded. Clinical information was determined by chart review. The metric of “cross-resistance” to the second ADC was defined as patients with progressive disease on first restaging assessment or progression within 60 days of treatment initiation. Every subsequent ADC beyond the first was compared against the prior ADC for presence of identical “antibody target” and “payload”. Comparisons across ADCs were performed using Fisher’s exact test. Significance was determined to be a type I error less than 0.05. A subset of patients had available whole exome tissue sequencing through commercially available sequencing platforms (BostonGene and Caris) performed around the time of receipt of ADC. All sequencing reports were examined for presence of pathogenic variants, variants of uncertain significance, and currently undefined variants and fusions as defined by each sequencing platform. Results: 68 patients were identified who received two or more ADCs for metastatic HR+/HER2- breast cancer or TNBC from August 2014-June 2023. 30 patients (44.1%) had HR+/HER2- disease and 38 patients (55.9%) had TNBC; 50 patients (73.5%) had HER2-low disease. Median age at time of second ADC was 59.6 (range 29.9-88.6). Patients had received a median of 4 lines of treatment in the metastatic setting prior to initiation of the second ADC. At time of first restaging, cross-resistance was present in 38/64 evaluable cases (59.4%). When the antibody target of the latter ADC was the same as the prior, cross-resistance was present in 11/14 cases (78.5%) compared to 26/49 cases (53.1%) when the later ADC targeted a different tumor-associated antigen. Relatively similar patterns of cross-resistance were observed regardless of whether the later ADC contained an identical payload to prior (6/10 cases, 60%) versus a different payload (22/42, 52.4%). Sequencing information was available for 20 patients who received multiple ADCs with 15 unique reports performed at the time of resistance to ADC1, prior to initiation of ADC2, or after ADC2 if presence of cross-resistance. Variants in topoisomerase-I associated genes (TOP1, TOP2A, TOP3A, TOP3B) were identified in a subset of patients mediating cross-resistance to the second ADC with a topoisomerase-I inhibitor payload. Conclusions: In this multi-institution study, cross-resistance to the second ADC appears to be driven by the antibody target in some patients versus the payload in others, highlighting the heterogeneity of mechanisms related to ADC resistance. Tumor sequencing revealed candidate resistance mutations that may guide optimal sequencing for patients with MBC. Citation Format: Rachel Occhiogrosso Abelman, Laura Spring, Geoffrey Fell, Andrew Davis, Whitney Hensing, Phoebe Ryan, Neelima Vidula, Seth Wander, Arielle Medford, Jennifer Shin, Elizabeth Abraham, Steven Isakoff, Beverly Moy, Leif Ellisen, Aditya Bardia. Sequencing Antibody-Drug Conjugate after Antibody-Drug Conjugate in Metastatic Breast Cancer (A3 study): Multi-Institution Experience and Biomarker Analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS08-03.

Outcome of video-assisted thoracoscopic treatment of idiopathic chylothorax in 15 cats.

To evaluate the outcomes and complications of video-assisted thoracoscopic (VATS) treatment of chylothorax in cats. Multi-institutional retrospective study. Fifteen client-owned cats. The medical records of cats undergoing thoracoscopic thoracic duct ligation (TDL) for treatment of idiopathic chylothorax were reviewed. Cats undergoing additional procedures including thoracoscopic pericardectomy and/or laparoscopic cisterna chyli ablation (CCA)_were included. Follow up was obtained through communication with the referring veterinarian or owner. All cats underwent thoracoscopic TDL. Thirteen cats underwent simultaneous pericardectomy and two cats underwent laparoscopic CCA without pericardectomy. Conversion from a thoracoscopic to open approach was necessary in 2/15 (13%) of thoracic duct ligations and 1/11 (9%) of pericardectomies. The most common postoperative complication was persistent pleural effusion in five cats (33%). Four of 15 cats (27%) died or were euthanized prior to hospital discharge following surgery. Recurrence of effusion occurred in 1/7 (14%) of cats that sustained resolution of the effusion at the time of surgery with a median follow up of 8 months. The overall mortality attributed to chylothorax was 47%. Thoracoscopic treatment of idiopathic chylothorax resulted in a low incidence of intraoperative complications or conversion in the study population; however, mortality related to feline idiopathic chylothorax remained high. While VATS treatment of idiopathic chylothorax is technically feasible, further consideration of the underlying pathology and current treatment algorithm is needed to improve outcomes as this remains a frustrating disease to treat in the feline population.

Abstract PO3-03-01: Impact of Environmental Temperature on Clinical Outcomes and Tumor Microenvironment of Early-Stage Breast Cancer

Abstract Background Preclinical evidence using mouse model suggests that thermal/cold stress increases tumor growth by modulating the tumor microenvironment (TME); however, the clinical relevance of temperature on breast cancer (BC) outcomes is unknown. Studies show that residing in cold regions is associated with higher incidence of BC. We aim to study the impact of environmental temperature on the pathological complete response (pCR) and survival of early-stage BC patients (pts). Methodology A multi-institutional study was conducted within the Oncology Research Information Exchange Network (ORIEN). We analyzed the clinical and genomic data for early-stage BC pts from 12 centers in different environment zones (5 warm and 7 cold) (based on average annual regional temperature obtained from National Centers for Environmental Information). Cox regression was used to measure the association of climate and overall/relapse-free survival (OS/RFS) after adjusting for age, race, body mass index, grade, stage, treatments, comorbidities, and subtype. Raw feature counts were normalized, and differential expression analysis was carried out using DESeq2, while adjusting for all of the covariates. Differential expression rank order was used for subsequent gene set enrichment analysis (GSEA), performed using the cluster profile package in R. Gene sets queried included the Hallmark, Canonical pathways, and GO Biological Processes Ontology collections available through the Molecular Signatures Database (MSigDB). Results Out of the 1,304 early-stage BC pts, 271 pts received neoadjuvant chemotherapy (NAC) (186 warm, 85 cold). Higher clinical T- and N-stages were observed in pts from warm compared to cold regions (p&amp;lt; 0.001). Pts residing in cold regions had more comorbidities (57.6% vs 4.8%, p&amp;lt; 0.001). Pts in warm regions had higher pCR, though not statistically significant (8% vs 2.5%, p= 0.1). In the overall population, the OS (univariate (UV) HR= 0.48, 95% CI 0.27-0.64, p &amp;lt; 0.001; adjusted HR (aHR)= 0.56, 95% CI 0.32 - 0.96, p= 0.03) and RFS (UV HR= 0.51, 95% CI 0.38 - 0.68, p&amp;lt; 0.001; aHR= 0.52, 95% CI 0.36 - 0.75, p= 0.0005) were higher in pts from warm compared to cold regions (Table 1). Among the patient subgroup treated with NAC, the OS (aHR= 0.35, p= 0.02) and RFS (aHR= 0.49, p= 0.02) of pts from warmer regions was also higher than cold regions. RNA sequencing was performed on 826 tumors (443 warm, 383 cold) using pre-treatment samples. Naïve B-cells (mean: 0.09 vs 0.08, p=0.004), CD4 naïve T cells (0.03 vs 0.02, p= 0.0008), CD4+ memory T cells (0.03 vs 0.02, p= 0.04), gamma-delta T-cells (0.007 vs 0.004, p= 0.006) were higher in pts residing in cold compared to warm regions while CD8 T cells, T regulatory cells, macrophages, dendritic cells, natural killer cells were similar in both regions. Macrophage signaling, cholesterol metabolism and the pathway for negative regulation of cell migration in angiogenesis were upregulated in pts living in warm compared to cold regions. Conclusion Early-stage BC pts living in cold have worse OS and RFS compared to warm regions. Our study is the first to report significant differences in the TME among these pts. However, it is important to acknowledge that the limited availability of comprehensive data regarding patients' relocation to different environmental temperature zones during treatments, and individual temperature preferences may be considered a potential limitation of our study. To ensure the validity and robustness of these intriguing findings, larger multi-center studies should be conducted, encompassing detailed information on the duration of exposure to both warm and cold weather conditions. Table 1: OS and RFS of patients living in warm vs cold environments Citation Format: Arya Mariam Roy, Spencer Rosario, Anthony George, Qiang Hu, Brian Czerniecki, John Carpten, Virginia Borges, Bryan Schneider, Jill Kolesar, Christopher Moskaluk, Craig Shriver, Cindy Matsen, Shridar Ganesan, Sneha Phadke, Wajeeha Razaq, Kristopher Attwood, Shipra Gandhi. Impact of Environmental Temperature on Clinical Outcomes and Tumor Microenvironment of Early-Stage Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-01.

Abstract PO4-27-08: A Phase II Multi-Institutional Study of Concurrent Radiotherapy, Palbociclib, and HormoneTherapy for Treatment of Bone Metastasis in Breast Cancer Patients

Abstract Background: This Phase II study aimed to determine the efficacy and safety of administering palliative radiotherapy (RT) to bone metastases (mets) in patients (pts) receiving concurrent palbociclib and hormone therapy (HT) for hormone receptor positive, Her2/neu negative breast cancer. The primary endpoint was response rate 3 months after RT. Methods: Pts with painful bone mets or asymptomatic bone mets with risk for impending clinical event were treated with RT to 30 Gy in 10 fractions or 20 Gy in 5 fractions with concurrent palbociclib and HT. Change in maximum pain score on the Brief Pain Inventory was used to assess pain response 3 months post RT relative to baseline. Among pts with asymptomatic bone lesions, response was defined as prevention of a clinical event (e.g., bone fracture) without evidence of local tumor growth on surveillance imaging. Patient reported outcomes (PROs) of fatigue, depression, anxiety, and quality of life were collected. Blood-based biomarkers were examined to determine their relationship with response and PROs. Using a non-inferiority study design, a sample size of at least 33 pts was needed to achieve 80% power to detect a non-inferiority proportion of 60% using a one-sided binomial test and assuming a Type I error of 0.05. Results: Among 38 patients enrolled, 79% had painful bone mets. 35 pts completed baseline and 3-month post RT assessments. 61% and 37% of pts received aromatase inhibitors and fulvestrant, respectively, with palbociclib. Median age was 60 years (31-83) and 25% of pts were non-Hispanic Black. The majority (72%) of pts received 5 fraction RT and 69% received RT to one bone region. 29 patients (83%) were responders [95% CI: 66%-93%, p=.003]. Median progression free survival (PFS) was 30.4 months (1.3 - 44.0). Three-year PFS and overall survival were 45.6% and 67.2%, respectively. Grade 3 neutropenia developed in 4 (11%), 4 (11%), and 7 (20%) pts at end of RT, 1 month, and 3 months post RT, respectively. No pts developed Grade 4 neutropenia. One patient developed Grade 3 gastrointestinal toxicity during RT, another developed Grade 3 dyspnea 1 month post XRT, and another developed a bone fracture 6 months after RT. &amp;gt;While patient reported measures of fatigue, depression, and overall quality of life did not significantly change during or after RT relative to baseline, pain scores (i.e., BPI pain severity and interference, BM22 pain characteristics and pain site subscales, EORTC C15 pain) significantly decreased 3 months post XRT relative to baseline. Heightened inflammatory marker levels (e.g., TNFRII, IL1ra, CRP, TNF alpha) were significantly associated with worse symptoms of fatigue (MFI) and depression (HADS), increased pain interference (BPI), and lower overall quality of life (SF-36), controlling for age and time using mixed effect models. Patients with improved pain symptoms and lower pain scores had significantly lower inflammatory marker levels relative to baseline (e.g., interleukin-6). Conclusions: Our study demonstrated high rates of response to concurrent RT with palbociclib and HT with acceptable levels of toxicity. These results suggest that RT to bone mets effectively alleviates pain in patients taking palbociclib and pain response to treatment is associated with decreased inflammatory markers. RT may be given to pts receiving palbociclib and HT for breast cancer. Clinical Trial Identification: NCT03691493 Citation Format: Mylin Torres, Jolinta Lin, Sarah Friend, Canhua Xiao, Yichun Cao, Shannon Kahn, Karen Godette, Sheela Hanasoge, David Yu, Tony Eng, Matthew Cheney, Nancy Wiggers, Andrew Pippas, Keerthi Gogineni, Jane Meisel, David Schuster, Aditya Bardia, Andrew Miller, Jennifer Felger, Jeffrey Switchenko, Amelia Zelnak, Kevin Kalinsky, Manali Bhave. A Phase II Multi-Institutional Study of Concurrent Radiotherapy, Palbociclib, and HormoneTherapy for Treatment of Bone Metastasis in Breast Cancer Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-27-08.

Abstract PO1-22-10: Long term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases

Abstract Background: The number of breast cancer patients in Japan undergoing immediate breast reconstruction (IBR) has increased and the postoperative follow-up period has been extended. This study was conducted to clarify the clinical aspects of and factors associated with local recurrence (LR) after IBR. Methods: This was a multicenter study which included 4153 early breast cancer patients who underwent IBR. Clinicopathological characteristics were examined and factors potentially contributing to LR were analyzed. Risk factors for LR were examined separately for non-invasive and invasive breast cancers. Results: The median follow-up period was 75 months. The 7-year LR rates were 2.1% and 4.3% for non-invasive and invasive cancers, respectively (p &amp;lt; 0.001). The proportions of LR detected by palpation, subjective symptoms, and ultrasonography were 40.0%, 27.3%, and 25.9%, respectively. Overall, 75.7% of LR were solitary, and 92.7% of these cases had no further recurrences during the observational period. Multivariate analysis of LR for invasive cancer showed that skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM), the presence of lymphovascular invasion, cancer at the surgical margin, and not receiving radiation therapy were factors related to LR. The 7-year overall survival rates of the patients with LR and non-LR of invasive cancers were 92.5% and 97.3%, respectively, (p=0.002). Conclusions: The rate of LR after IBR was acceptably low and IBR can thus be performed safely for early breast cancer patients. Invasive cancer, SSM/NSM, lymphovascular invasion, and/or cancer at the surgical margin should prompt awareness of the possibility of LR. Citation Format: Akiko Ogiya, Naomi Nagura, Ayaka Shimo, Hiroko Nogi, Kazutaka Narui, Hirohito Seki, Hiroki Mori, Shinsuke Sasada, Makoto Ishitobi, Naoto Kondo, Chikako Yamauchi, Kohei Akazawa, Tadahiko Shien. Long term outcomes of breast cancer patients with local recurrence after mastectomy undergoing immediate breast reconstruction: A retrospective multi-institutional study of 4153 cases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-10.

Factors Associated With Family Decision-Making After Pediatric Out-of-Hospital Cardiac Arrest

AimThis study aims to identify demographic factors, area-based social determinants of health (SDOH), and clinical features associated with medical decision-making after pediatric out-of-hospital cardiac arrest (OHCA). MethodsThis is a retrospective, exploratory, descriptive analysis of patients < 18 years old admitted to the pediatric intensive care unit (ICU) after OHCA from 2011 to 2022 (n=217) at an urban tertiary care, free-standing children’s hospital. Outcomes of interest included: (1) whether a new advance care plan (ACP) (defined as a written advance directive including do not resuscitate and/or do not intubate) was ordered during hospitalization, and (2) whether the patient was discharged with new medical technology (defined as tracheostomy and/or feeding tube). Logistic regression models identified features associated with these outcomes. ResultsOf the 217 patients, 78 patients (36%) had a new ACP placed during their admission. Of the survivors, 26% (27/102) were discharged home with new medical technology. Factors associated with ACP were greater change in Pediatric Cerebral Performance Category (PCPC) score (aOR=1.49, 95% CI [1.28-1.73], p-value <0.001) and palliative care consultation (aOR = 2.39, 95% CI [1.16-4.89], p-value 0.018). Factors associated with new medical technology were lower change in PCPC score (aOR=0.76, 95% C.I. [0.61-0.95], p-value=0.015) and palliative care consultation (aOR = 7.07, 95% CI [3.01-16.60], p-value <0.001). There were no associations between area-based SDOH and outcomes. ConclusionsUnderstanding factors associated with decision-making related to ACP after OHCA is critical to optimize counseling for families. Multi-institutional studies are warranted to identify whether these findings are generalizable.

Unrecognized Focal Nonmotor Seizures in Adolescents Presenting to Emergency Departments.

Many adolescents with undiagnosed focal epilepsy seek evaluation in emergency departments (EDs). Accurate history-taking is essential to prompt diagnosis and treatment. In this study, we investigated ED recognition of motor vs nonmotor seizures and its effect on management and treatment of focal epilepsy in adolescents. This was a retrospective analysis of enrollment data from the Human Epilepsy Project (HEP), an international multi-institutional study that collected data from 34 sites between 2012 and 2017. Participants were 12 years or older, neurotypical, and within 4 months of treatment initiation for focal epilepsy. We used HEP enrollment medical records to review participants' initial diagnosis and management. A total of 83 adolescents were enrolled between 12 and 18 years. Fifty-eight (70%) presented to an ED before diagnosis of epilepsy. Although most ED presentations were for motor seizures (n = 52; 90%), many patients had a history of nonmotor seizures (20/52 or 38%). Adolescents with initial nonmotor seizures were less likely to present to EDs (26/44 or 59% vs 32/39 or 82%, p = 0.02), and nonmotor seizures were less likely to be correctly identified (2/6 or 33% vs 42/52 or 81%, p = 0.008). A history of initial nonmotor seizures was not recognized in any adolescent who presented for a first-lifetime motor seizure. As a result, initiation of treatment and admission from the ED was not more likely for these adolescents who met the definition of epilepsy compared with those with no seizure history. This lack of nonmotor seizure history recognition in the ED was greater than that observed in the adult group (0% vs 23%, p = 0.03) and occurred in both pediatric and nonpediatric ED settings. Our study supports growing evidence that nonmotor seizures are often undiagnosed, with many individuals coming to attention only after conversion to motor seizures. We found this treatment gap is exacerbated in the adolescent population. Our study highlights a critical need for physicians to inquire about the symptoms of nonmotor seizures, even when the presenting seizure is motor. Future interventions should focus on improving nonmotor seizure recognition for this population in EDs.

A Multi-Institutional Study Comparing Stoma Location in Neonates With Intestinal Perforation

IntroductionNeonates with intestinal perforation often require laparotomy and intestinal stoma creation, with the stoma placed in either the laparotomy incision or a separate site. We aimed to investigate if stoma location is associated with risk of postoperative wound complications. MethodsA multi-institutional retrospective review was performed for neonates ≤3 mo who underwent emergent laparotomy and intestinal stoma creation for intestinal perforation between January 1, 2009 and April 1, 2021. Patients were stratified by stoma location (laparotomy incision versus separate site). Outcomes included wound infection/dehiscence, stoma irritation, retraction, stricture, and prolapse. Multivariable regression identified factors associated with postoperative wound complications, controlling for gestational age, age and weight at surgery, and diagnosis. ResultsOverall, 79 neonates of median gestational age 28.8 wk (interquartile range [IQR]: 26.0-34.2 wk), median age 5 d (IQR: 2-11 d) and median weight 1.4 kg (IQR: 0.9-2.42 kg) had perforated bowel from necrotizing enterocolitis (40.5%), focal intestinal perforation (31.6%), or other etiologies (27.8%). Stomas were placed in the laparotomy incision for 41 (51.9%) patients and separate sites in 38 (48.1%) patients. Wound infection/dehiscence occurred in 7 (17.1%) neonates with laparotomy stomas and 5 (13.2%) neonates with separate site stomas (P = 0.63). There were no significant differences in peristomal irritation, stoma retraction, or stoma stricture between the two groups. On multivariable regression, separate site stomas were associated with increased likelihood of prolapse (odds ratio 6.54; 95% confidence interval: 1.14-37.5). ConclusionsStoma incorporation within the laparotomy incision is not associated with wound complications. Separate site stomas may be associated with prolapse. Patient factors should be considered when planning stoma location in neonates undergoing surgery for intestinal perforation.

Multi-Institutional Study Evaluating the Role of Circulating Tumor DNA in the Management of Appendiceal Cancers.

Conventional surveillance methods are poorly sensitive for monitoring appendiceal cancers (AC). This study investigated the utility of circulating tumor DNA (ctDNA) in evaluating systemic therapy response and recurrence after surgery for AC. Patients from two specialized centers who underwent tumor-informed ctDNA testing (Signatera) were evaluated to determine the association between systemic therapy and ctDNA detection. In addition, the accuracy of ctDNA detection during surveillance for the diagnosis of recurrence after complete cytoreductive surgery (CRS) for grade 2-3 ACs with peritoneal metastases (PM) was investigated. In this cohort of 94 patients with AC, most had grade 2-3 tumors (84.0%) and PM (84.0%). Fifty patients completed the assay in the presence of identifiable disease, among which ctDNA was detected in 4 of 7 (57.1%), 10 of 16 (62.5%), and 19 of 27 (70.4%) patients with grade 1, 2, and 3 diseases, respectively. Patients who had recently received systemic chemotherapy had ctDNA detected less frequently (7 of 16 [43.8%] v 26 of 34 [76.5%]; odds ratio, 0.22 [95% CI, 0.06 to 0.82]; P = .02). Among 36 patients with complete CRS for grade 2-3 AC-PM, 16 (44.4%) developed recurrence (median follow-up, 19.6 months). ctDNA detection was associated with shorter recurrence-free survival (median 11.3 months v not reached; hazard ratio, 14.1 [95% CI, 1.7 to 113.8]; P = .01) and showed high accuracy for the detection of recurrence (sensitivity 93.8%, specificity 85.0%). ctDNA was more sensitive than carcinoembryonic antigen (62.5%), CA19-9 (25.0%), and CA125 (18.8%) and was the only elevated biomarker in four (25%) patients with recurrence. This study revealed a reduced ctDNA detection frequency after systemic therapy and accurate recurrence assessment after CRS. These findings underscore the role of ctDNA as a predictive and prognostic biomarker for grade 2-3 AC-PM management.

First-line immune combination therapies for non-clear cell vs. clear cell metastatic renal cell carcinoma: Real-world multicenter data from Germany

IntroductionThe aim was to compare treatment outcomes of clear cell metastatic renal cell carcinoma (ccmRCC) vs. non-ccmRCC (nccmRCC) patients who received first-line immune combination therapies. MethodsWithin our retrospective multi-institutional consecutive database of eight tertiary-care centers, we identified mRCC patients treated with first-line immune combination therapies between 11/2017 and 12/2022. Using log-rank analysis and multivariable Cox regression, we tested for differences in overall survival (OS) and progression-free survival (PFS) of nccmRCC vs. ccmRCC patients. Covariables consisted of age at diagnosis, sex, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups, Eastern Cooperative Oncology Group (ECOG) status and sarcomatoid feature. ResultsOf 289 study patients, 39 (13%) patients harbored nccmRCC. Median OS was 37 months vs. not reached for ccmRCC vs. nccmRCC patients (p=0.6). Median PFS was 13 vs.15 months (p=0.9). Multivariable Cox regression models did not identify nccmRCC as an independent predictor of higher overall mortality in mRCC patients (Hazard Ratio [HR]: 1.23; p=0.6) or a higher progression rate (HR: 1.0; p=1.0). ConclusionIn our real-world multi-institutional study, no differences between ccmRCC and nccmRCC patients receiving first-line immune combination treatment were observed, even after adjustment for important patient and tumor characteristics. More prospective trials in nccmRCC patients are needed. Micro abstractIn our German mutiinstitutional retrospective study of 289 mRCC patients with 39 (13%) patients harbored non-clear cell metastatic renal cell carcinoma, no significant overall or progression-free differences were observed between nccmRCC and clear cell metastatic renal cell carcinoma (ccmRCC) groups undergoing first-line immune combination therapy, indicating similar outcomes regardless of histological type.

Prognostic value of preoperative combined neutrophil, monocyte, and lymphocyte scores in patients with renal cell carcinoma undergoing laparoscopic nephrectomy: A retrospective study.

In a multi-institutional clinical study, we assessed the prognostic significance of a novel indicator preoperative peripheral blood immune (PBIS) scores that combined ratios of preoperative lymphocyte, monocyte, and neutrophil of renal cell carcinoma (RCC) patients undergoing laparoscopic nephrectomy. Between January 2014 and December 2019, 438 patients with RCC were retrospectively analyzed in three centers. We used X-tile software to obtain the optimum cut-off values for neutrophils, monocytes, and lymphocytes to classify the patients. To assess the relationship between PBIS score and overall survival (OS), and cancer-specific survival (CSS) in patients with RCC by Kaplan-Meier survival curves and Cox regression analyses. In addition, predictive OS and CSS nomograms were constructed. The discriminative ability of nomogram and predictive performance accuracy were verified with consistency index (C-index), calibration curves, receiver operating curve (ROC) curves, decision curve analysis (DCA) curves, and time-dependent ROC curves. The optimum cutoff values for monocytes, lymphocytes, and neutrophils were 0.46, 1.01, and 4.50, respectively. We divided patients into four subgroups according to PBIS scores, which were significantly associated with M-stage (p = 0.008), T-stage (p < 0.001), N-stage (p = 0.006), and AJCC stage (p < 0.001). Multivariate Cox regression analysis revealed that RCC patients with lower PBIS scores showed a worse postoperative prognosis and served as an independent predictor of OS (p = 0.002) and CSS (p < 0.001). Ultimately, the nomograms based on PBIS scores demonstrated excellent predictive performance for OS (C-index: 0.770) and CSS (C-index: 0.828) through the analysis of calibration curves, ROC curves, DCA curves, and time-dependent ROC curves. PBIS score served as novel and effective predictor to accurately predict OS and CSS in patients with RCC receiving laparoscopic nephrectomy.