Baptist Health South Florida

Immunotherapy with checkpoint inhibitors targeting the PD1/PD-L1 and CTLA4 pathways has limited activity in patients with microsatellite stable (MSS) colorectal adenocarcinoma (CRC). In a prior study, the combination of cetuximab and pembrolizumab failed to improve outcomes for patients with advanced RAS wild-type (RASwt) CRC. In this post hoc secondary analysis, we show that the cetuximab and pembrolizumab-treated patients with TP53 mutant (p53mt) tumors had significantly higher progression-free survival (PFS) and a decrease in tumor burden compared to patients with TP53 wild-type (p53wt) tumors but no difference in overall survival compared to patients with p53wt tumors. The gene set enrichment analysis showed a uniform upregulation of multiple metabolic and immune gene sets, including NK-mediated immunity and IL-12 pathway, while the IL6 pathway was downregulated. There were no overlapping transcriptional alterations between the p53mt and p53wt groups with treatment that remain constant despite the therapeutic intervention. Functional overlap with treatment in both groups in the proliferative, immune, and metabolic pathways were identified. In the baseline tumor samples, the number of PD-L1+ tumor cells was significantly higher in p53mt tumors while the number of OX40-/AE1_AE3-/PD-L1- non-tumor cells, positive for either LAG3, CTLA4 or TIM3, was significantly higher in p53wt tumors. In conclusion, TP53 status was prognostic of improved PFS with cetuximab plus pembrolizumab in RASwt CRC. Future studies evaluating immune-oncology agents in patients with MSS, RASwt CRC should include TP53 as an integrated biomarker and evaluate its performance as a positive predictive biomarker (ClinicalTrials.gov NCT02713373).

For patients with advanced breast cancer (ABC), standard-of-care (SOC) treatment in first line (1L) with CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) is well established. However, data on treatment patterns in second line (2L), where the treatment landscape is evolving, are lacking. This large real-world study investigated treatment sequencing from 1L to 2L in patients with HR+/HER2- ABC in the post-CDK4/6i era. Data leveraged the Adelphi ABC Disease Specific Programme (DSP)™, a cross-sectional survey conducted in Europe and the United States between July 2022 and March 2023. Physicians provided data for consecutively consulting patients, including current and historic clinical status, treatment sequencing and biomarker testing history. All analyses were descriptive. Data for 767 patients with HR+/HER2- ABC receiving 2L treatment at data collection were analyzed. In 2L, 31.6% received chemotherapy-based regimens, 17.7% received ET monotherapy, 21.5% received CDK4/6i+ET, and 26.3% received a targeted therapy (mTOR/PARP/PI3K inhibitors). Of those receiving 2L, 58% previously received a CDK4/6i regimen in 1L, in line with treatment guidance, while 21% received chemotherapy. Use of targeted therapies in 2L was driven by biomarker testing. Country/region-specific variation in biomarker testing and treatments were likely due to differences in local guidance and practice. This study provides insights into treatment sequencing in patients with HR+/HER2- ABC who progress to 2L in the post-CDK4/6i era. For patients without targetable mutations, there is no clear SOC at 2L and treatment options are limited. New treatments may further shape this developing landscape.

Diagnosing acute appendicitis during pregnancy is challenging due to physiological changes and concerns regarding fetal radiation exposure from Computed Tomography (CT). This systematic review and meta-analysis evaluates the diagnostic accuracy and safety of Magnetic Resonance Imaging (MRI) for suspected acute appendicitis, providing an updated synthesis based on a large dataset and modern MRI protocols. Following PRISMA guidelines and PROSPERO registration, we performed a systematic review and diagnostic meta-analysis. Studies involving pregnant women with suspected appendicitis, extractable diagnostic accuracy data (true positives, false positives, false negatives, true negatives), and surgical/histopathological confirmation were included. PubMed, EMBASE, and Cochrane Central were systematically searched until September 3, 2025. Risk of bias was assessed using QUADAS-2, and evidence certainty with GRADE. Statistical analysis used R, employing bivariate random-effects models for sensitivity/specificity, sROC curves, meta-regression, and Deeks' test for publication bias. Thirty-four studies were included. Pooled sensitivity was 0.95 (95% CI: 0.91-0.98; I² = 0%) and pooled specificity 0.97 (95% CI: 0.96-0.98; I² = 55.3%), demonstrating strong diagnostic performance (AUC = 0.961; Diagnostic Odds Ratio = 273.1). A positive MRI result increased post-test probability from 30% to 93%, while a negative result reduced it to 2.2%. QUADAS-2 revealed patient selection and index-test interpretation as common bias sources, particularly in older retrospective studies. Moderate heterogeneity in specificity (I² = 55.3%) was observed, but not explained by gestational age. Deeks' test indicated potential publication bias (p = 0.0024), though pooled estimates remained robust in sensitivity analyses. Non-contrast MRI is a highly accurate and safe diagnostic tool for suspected acute appendicitis in pregnancy, demonstrating performance comparable to CT in non-pregnant populations. We recommend MRI as the standard second-line imaging modality following inconclusive ultrasound findings to enhance diagnostic confidence, minimize fetal radiation exposure, and reduce unnecessary surgical interventions.

In the PROACTIVE-HF trial, remote heart failure (HF) management using comprehensive vital signs and seated mean pulmonary artery pressure (mPAP) was safe and resulted in a low reported rate of HF hospitalization (HFH) and all-cause mortality (HFH/D) through 12 months. In this report, we extend the results from the PROACTIVE-HF study through 2 years, stratified by ejection fraction (EF). PROACTIVE-HF was a prospective, multicenter, open-label, single-arm trial evaluating the safety and efficacy of patient management using the Cordella PA pressure sensor system in patients with New York Heart Association class III symptoms, regardless of EF. In the first 24 months, the incidence of HF events (HFE)/D was 0.89 (95% CI 0.81-0.99) events per patient, driven by HFH. Patients with HF with reduced EF had greater HFE/D rates than those with HF with preserved EF (1.0 vs 0.8 events per patient, P = .048). For patients with HF experiencing moderate-to-severe symptoms, management using the Cordella PA sensor system was associated with low event rates and improved health status at 2 years, regardless of EF. Comprehensive remote monitoring of vital signs, seated PAP, and patient-reported symptoms via a digital platform supports sustained benefit for high-risk patients with HF.

474 Background: Metastatic non–clear cell renal cell carcinoma (nccRCC) is a rare, heterogeneous disease historically underrepresented in trials. Over the past two decades, systemic therapies including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (IO), and IO/TKI combinations have expanded, but their impact on survival in nccRCC remains poorly defined. Methods: We included patients diagnosed with metastatic nccRCC between 2004-2020 from National Cancer Database. We stratified patients based on therapy eras: pre-TKI, TKI, IO, and IO–TKI. We utilized Kaplan-Meier analysis and Cox proportional hazard models to study overall survival (OS)in patients with nccRCC. Results: We included 2,753 patients diagnosed with metastatic nccRCC from the NCDB. Among patients with nccRCC, those who did not receive systemic therapy had a median survival of 3.29 months (95% CI: 2.99–3.55 months). In contrast, patients who received systemic therapy had a longer median survival of 7.62 months (95% CI: 7.26–7.98 months). At 6 months, patients who did not receive systemic therapy had a survival probability of 32.9% (95% CI: 29.9–35.9%). By 12 months, survival declined further to 16.9% (95% CI: 14.7–19.5%). In contrast, patients who received systemic therapy demonstrated significantly better outcomes. At 6 months, survival probability was 62.1% (95% CI: 59.5–64.6%), and at 12 months, survival remained 27.6% (95% CI: 25.3–30.0%). Patients who received systemic therapy had 18% less risk of death compared to patients who did not receive systemic therapy. Additionally, each subsequent year of diagnosis had HR of 0.96 (95% CI: 0.95–0.97, p = 0.00) compared to previous year. Conclusions: Patients with metastatic nccRCC who received systemic therapy lived longer than those who did not (median 7.6 vs 3.3 months; ~18% lower mortality risk). Year-over-year survival gains (HR 0.96; p<0.001) align with wider use of TKIs, IO, and IO–TKI regimens. Given persistently modest survival, prioritizing enrollment in subtype-specific trials and ensuring timely access to active combinations should be central to care. Cox proportional hazards model evaluating factors associated with overall survival among patients with metastatic nccRCC. Variable Comparator HR (95% CI) P-value Age ≥65 years vs <65 years 1.02 (0.91–1.13) 0.78 Private insurance vs Uninsured 0.78 (0.60–1.01) 0.06 Non-academic facility vs Academic 1.13 (1.04–1.23) <0.001 Comorbidity ≥1 vs 0 1.07 (0.98–1.17) 0.13 Distance ≥50 miles vs <50 miles 0.87 (0.79–0.96) <0.001 Poor/Undifferentiated grade vs Well/Moderate 1.72 (1.50–1.97) <0.001 Cytoreductive nephrectomy: Yes vs No 0.46 (0.41–0.53) <0.001 Each Year of diagnosis vs Previous Year 0.96 (0.95–0.97) <0.001 Systemic therapy: Yes vs No 0.82 (0.76–0.89) <0.001

National data show that about 250 preschoolers are suspended or expelled daily in the United States. Jump Start is a multi-tiered infant and early childhood mental health consultation program that strengthens early care and education centers' capacity to support children's social-emotional development and prevent school suspension and expulsion. This retrospective study examined center-level exclusionary discipline practices, Jump Start participation, and related changes in discipline and expulsion policies. Data from 270 early care and education centers across Miami-Dade County that received Jump Start services during one of three academic years (2022-2023, 2023-2024, or 2024-2025) were included. Analyses examined associations between baseline exclusionary discipline practices, program duration, discipline and expulsion policy changes, and post-Jump Start exclusionary discipline practices. Statistically significant reductions were observed in the frequency of traditional suspensions/expulsions and soft expulsions following Jump Start participation. The association between the Jump Start duration and post-Jump Start soft expulsions was significantly moderated by changes in center discipline policies, such that Jump Start was effective at reducing soft expulsions only when discipline policies showed meaningful improvement. Infant and early childhood consultation models, such as Jump Start, show promise in reducing exclusionary discipline practices, especially when implementation improves discipline policies.

Abstract Background: Brain metastases (BrM) are a frequent and clinically challenging manifestation of HER2-positive (HER2+) metastatic breast cancer (mBC), affecting up to 50% of patients (pts) over the course of their disease. Current guidelines recommend trastuzumab deruxtecan (T-DXd) as the preferred second-line therapy for HER2+ mBC overall, while the combination of tucatinib, trastuzumab, and capecitabine (TTC) remains an important option for pts with active or progressing BrM disease due to its proven intracranial activity. However, there is a lack of real-world data comparing treatment outcomes with these regimens specifically among pts with BrM involvement. This study evaluates real-world time to next treatment (TTNT) in pts with prior HER2+ therapy and documented BrM treated with second-line T-DXd vs TTC. Methods: We used the IntegraConnect PrecisionQ de-identified electronic health record database, which includes data on over 3 million cancer pts across more than 500 care sites, to identify individuals with HER2+ mBC who received either T-DXd or TTC as second-line therapy on or after January 1, 2020. Eligible pts had documented BrM prior to initiating second-line treatment. HER2+ status was inferred based on receipt of at least one HER2-targeted therapy during first-line metastatic treatment. Individuals who received T-DXd in their first-line of metastatic therapy were excluded from the analysis. The index date was defined as the start of second-line therapy with either TTC or T-DXd. Descriptive statistics were used to summarize demographic and clinical characteristics by treatment group, including age at index date, race, ethnicity, health insurance, BMI, ECOG performance status, estrogen receptor status, first-line metastatic regimen (grouped as ado-trastuzumab emtansine, trastuzumab (H) +pertuzumab (P) + taxane, endocrine therapy +/- HP, or other regimens), and presence of liver, bone, or lung metastases. TTNT was analyzed using Kaplan-Meier survival curves, with median estimates reported. Multivariable Cox proportional hazards regression was used to evaluate the association between treatment and TTNT, adjusting for the aforementioned demographic and clinical covariates. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) are presented. Results: A total of 255 pts met study eligibility, of whom 138 (54%) received T-DXd as second-line therapy. Pts treated with T-DXd were slightly older than those who received TTC (median age: 58 vs 55 years; Wilcoxon p=0.026). A lower proportion of pts in the T-DXd group were classified as overweight (BMI 25-30) compared to the TTC group (17% vs 29%; chi-square p=0.026). No other significant differences in demographic or clinical characteristics were observed between treatment groups. Median TTNT was significantly longer among pts who received T-DXd compared to TTC (17 vs 11 months; log-rank p=0.006). This difference remained significant after adjustment for demographic and clinical covariates, with T-DXd associated with a 48% reduced likelihood of requiring subsequent therapy (HR: 0.52; 95% CI: 0.37-0.74; p<0.001). Conclusions: In this real-world analysis of pts with prior HER2+ therapy and documented BrM, second-line treatment with T-DXd was associated with significantly longer TTNT compared to TTC among pts with BrM. These findings may help inform treatment decisions in this high-risk population. However, interpretation is limited by the retrospective design, potential selection bias, and the use of treatment patterns to infer HER2 status. Most importantly, granular clinical data on BrM, including prior local therapies (radiation and/or surgery) and CNS-specific outcomes, were unavailable. Further prospective studies are needed to validate these findings. Citation Format: V. Gorantla, R. Choksi, F. Kudrik, D. Patt, S. Reddy, S. Reganti, S. Rosenfeld, G. Cioffi, T. Sura, D. Parris, A. Rui, M. Gart, C. Wall, B. Wang, P. Varughese, J. Donegan, L. Morere, R. Geller, J. Scott, R. Mahtani. Real-world time to next treatment in HER2+ breast cancer patients with brain metastases: trastuzumab deruxtecan vs tucatinib based therapy as second-line treatment [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-01-12.

Abstract Background: According to recent findings from the DESTINY-06 trial, HR-positive (HR+)/HER2-low metastatic breast cancer (mBC) patients (pts) who received trastuzumab deruxtecan (T-Dxd) following ≥1 line of endocrine therapy (ET) experienced improved progression-free survival (PFS) compared to those who received chemotherapy (chemo) in a second-line (2L) setting. To assess whether similar benefits are seen in a real-world setting, we evaluated overall survival (OS) and time to next treatment (TTNT). TTNT was used as a surrogate measure for PFS. Methods: We used the IntegraConnect PrecisionQ de-identified electronic health record database of >3 million cancer pts across >500 care sites, to identify pts. Eligible pts for the study were adults with a confirmed diagnosis of HR+/HER2-low mBC who had ≥2 documented visits and a CDK4/6 inhibitor(i) +/- ET in the first-line metastatic setting. Pts with a subsequent treatment (2L) with T-Dxd or chemo were identified and observed between 6-1-2022 and 4-30-2025. TTNT was defined as time from the 2L start to either the initiation of a subsequent line of therapy or death. We did not assess for the reason pts discontinued (e.g., toxicity or disease progression). TTNT and OS were analyzed using Kaplan-Meier analysis. Hazard ratios (HR) adjusting for age at treatment and race were estimated using Cox proportional hazard models. Results: Among 340 eligible pts, 82 received TDxd and 248 received chemo in the 2L setting. The median age at treatment was 64 (interquartile range 55, 70) years old with a composition of 70.0% White, 10.6% African American. Among pts with a reported Eastern Cooperative Oncology Group (ECOG) status at treatment, 91.5% had an ECOG score of ≤1. Median OS was not significantly different for pts who received T-Dxd compared to chemo (Table), but median TTNT was significantly longer for pts who received T-Dxd (10.1 months, 95% CI: 7.8, 13.1) compared to chemo (6.0 months, 95% CI: 5.1, 6.5). Pts using T-Dxd were significantly less likely to change treatment compared to chemo after adjusting for age, and race [HR (95% CI): 0.45 (0.30, 0.66), P<0.01)]. Treatment crossover occurred in both cohorts: 28% of pts in the chemo group utilized T-Dxd in a later line of therapy, and 19% of pts in the T-Dxd group utilized chemo in a later line of therapy. Conclusions: Consistent with findings from a subset of the Destiny-06 trial, HR+/HER2-low mBC pts previously treated with a CDK4/6i who then utilized T-Dxd in the 2L setting were associated with a significantly improved TTNT compared to 2L chemo utilization. OS was not statistically different between T-Dxd and Chemo. These results may be impacted by unmeasured factors such as, tumor burden, endocrine resistance, and access to care. Further studies are needed to confirm the optimal sequencing of TDxd in the real-world setting. Citation Format: R. Mahtani, R. Choksi, F. Kudrik, D. Patt, S. Reddy, S. Reganti, S. Rosenfeld, S. W. Champaloux, D. Parris, A. Rui, A. Sharma, M. Gart, C. Wall, B. Wang, P. Varughese, J. Donegan, L. Morere, R. Geller, J. Scott, V. Gorantla. Real-world comparison of time to next treatment for patients with HR-positive, HER2-low metastatic breast cancer treated with either chemotherapy or trastuzumab deruxtecan in the second-line [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-11-17.