Morton Plant Hospital is a 687-bed hospital at 300 Pinellas Street in Clearwater, Florida. Morton Plant Hospital is community-based and provides services in more than fifty specialty areas. This hospital is part of the greater BayCare Health System. Morton Plant Hospital.
BACKGROUND:Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement for patients with symptomatic severe aortic stenosis. However, long-term outcomes data are lacking for TAVR, particularly with newer-generation transcatheter heart valves. OBJECTIVES:The purpose of this study was to compare 10-year outcomes of intermediate-risk patients who underwent TAVR with the third-generation, balloon-expandable SAPIEN 3 valve in the PARTNER 2 SAPIEN 3 Intermediate-risk Registry (P2S3i) with those who underwent surgery in the PARTNER 2A (P2A) randomized trial. METHODS:Intermediate-risk patients were enrolled in the P2A trial from 2011 through 2013 and in the P2S3i registry in 2014. These prospective, multicenter studies used the same eligibility criteria and stratified patients based on suitability for transfemoral or transthoracic (transapical/transaortic) access. Ten-year outcomes were evaluated, including all-cause mortality, aortic valve reintervention, and core laboratory-adjudicated echocardiographic outcomes. Patient reconsent was required at 5 years for extended 10-year follow-up, and vital status sweeps were implemented to improve data completeness for all-cause mortality. To account for potential baseline differences and reduce confounding, P2S3i TAVR patients were propensity score-matched 1:1 to P2A surgical patients. RESULTS:Among 2,005 patients who received a valve, 1,069 underwent TAVR in P2S3i and 936 underwent surgery in P2A. After propensity score matching (N = 783 patients in each group), baseline characteristics were similar between groups: mean age was approximately 82 years, 43% were female, and mean Society of Thoracic Surgeons score was 5.5%. At 10 years, all-cause mortality rate was 83.4% after TAVR and 82.3% after surgery, respectively (HR: 1.01 [95% CI: 0.91-1.13]; P = 0.82). Aortic valve reintervention rates adjusted for competing mortality were 2.0% for TAVR and 1.9% for surgery (P = 0.47). Among 32 TAVR and 30 surgical patients with available echocardiographic data at 10 years, mean gradients were 11.0 mm Hg and 12.6 mm Hg, respectively. CONCLUSIONS:At 10 years, TAVR with the SAPIEN 3 valve and surgery resulted in similar rates of mortality and aortic valve reintervention, and similar hemodynamics in intermediate-risk patients with symptomatic severe aortic stenosis. This analysis highlights challenges associated with extended long-term follow-up of clinical trials, including differential loss to follow-up and the competing risk of mortality in elderly populations. (PARTNER 2A Trial; NCT01314313; PARTNER 2 SAPIEN 3 Intermediate-Risk Registry; NCT03222128).
Purpose/Objective(s) Radiotherapy (RT) is a central component of treatment for pediatric brain tumors but is prescribed using histology-driven doses without accounting for underlying biologic heterogeneity. The radiosensitivity index (RSI) and genomic-adjusted radiation dose (GARD) have been validated in adult cancers to quantify intrinsic radiosensitivity and biological radiation effect, but their role in pediatric CNS tumors is not well defined. We therefore evaluated RSI-driven tumor biology and assessed whether GARD predicts RT response in pediatric brain tumors to inform biologically personalized radiotherapy in this population. Materials/Methods We performed a retrospective analysis of samples from the Children’s Brain Tumor Network (CBTN). RSI was generated from a 10-gene expression signature and integrated into GARD through the linear-quadratic model. Top-quartile RSI samples was compared to bottom-quartile RSI samples utilizing differential gene expression, pathway analyses and cellular deconvolution. Cox proportional hazards models were used applying GARD as a continuous variable with overall survival and local recurrence as endpoints. Results The cohort included 69 high-grade glioma, 64 ependymoma, and 74 medulloblastoma patients. Median age was 8.9 years old. Medulloblastoma was predicted to be most radioresistant (RSI = 0.75), followed by high-grade glioma (RSI = 0.54), and ependymoma (RSI = 0.49). While RT dose was uniform across tumor types (Median: 54 Gy, SD: 2.5 Gy), GARD varied widely (Median: 16.2, SD: 9.7), Radiosensitive tumors were enriched for immune and inflammatory signaling programs, including TNF-α, IFN-γ, and related inflammatory pathways (all p < 0.001), relative to radioresistant tumors. Deconvolution analyses further demonstrated increased microglial and endothelial cell fractions in radiosensitive tumors (p < 0.001), consistent with a distinct immune–microenvironmental phenotype. GARD was independently associated with improved overall survival (HR = 0.96/unit, p = 0.04) and local recurrence (HR = 0.95/unit, p < 0.001), corresponding to a 35% reduction in mortality risk and 50% reduction in recurrence risk per 10-unit increase. Conclusion Radiosensitivity in pediatric brain tumors demonstrates strong biologic heterogeneity characterized by immune and microenvironmental signaling differences. Additionally, GARD was significantly associated with overall survival and local recurrence, supporting its utility as a biologically informed predictor of radiation effect. These findings suggest RSI- and GARD-based approaches may facilitate biologically personalized radiotherapy dose strategies in pediatric central nervous system tumors.
Purpose/Objective(s) Recent trials (e.g., CALGB-9343, PRIME II, LUMINA, IDEA, DEBRA) support omitting radiotherapy (RT) in select post-menopausal women with early breast cancer, relying on endocrine therapy (ET) alone post-lumpectomy. However, NSABP-B21 showed RT superior to ET for ipsilateral breast tumor recurrence (IBTR), and NCDB analyses in women aged 70 years or older indicate no 5-year overall survival difference between RT and ET monotherapies. ET has significant side effects and variable compliance, while ultra-hypofractionated RT/APBI is safe and convenient. We evaluated IBTR and other recurrence outcomes in post-menopausal breast cancer patients meeting RT-omission criteria but treated with APBI, stratified by endocrine therapy compliance, to assess potential for ET de-escalation. Materials/Methods Retrospective review of post-menopausal patients with early-stage invasive breast cancer treated with lumpectomy + SLNB + HDR brachytherapy APBI (34 Gy/10 fx BID, 2010-2022) at a single community center. Subsets meeting LUMINA criteria (age ≥55 y, T1N0, grade 1-2, luminal A surrogate: ER≥1%, PR>20%, HER2-, Ki67≤13.25%; n=131) and non-eligible (n=499) were stratified by ET duration: APBI only/short ET (≤91 d) vs. APBI + long ET (≥1795 d, ∼5 y). Patients with ER/PR <1% were excluded from ET compliance analysis (n=45). Primary outcome: IBTR. Secondary: contralateral breast tumor recurrence (CBTR), regional recurrence (RR), distant recurrence (DR). Kaplan-Meier and log-rank tests were used. Results Median follow-up was 95.9 months (8.0 years) (range 1.6–189 months). Crude recurrence rates are shown below: Among LUMINA-eligible patients, 5- and 10-year IBTR were 0% and 0% with ≤91 days ET versus 2.3% and 2.3% with long ET (p=0.355). Among non-eligible patients, 5- and 10-year IBTR were 8.8% and 23.9% versus 0% and 3.5% with long ET (p<0.001). Sensitivity analysis of short endocrine adherence extended to ≤1 year showed IBTR of 4.3% (2/46), still comparable to long ET. No significant differences in CBTR, RR, or DR within strata. Conclusion In LUMINA-eligible patients treated with APBI, adjuvant endocrine therapy provided no meaningful benefit (0% IBTR with short/no ET ≤3 months vs. 4.5% with long ET). In non-eligible patients, long ET significantly reduced IBTR (17.6% vs. 3.9%, p<0.01). These results support de-escalation of ET in low-risk cases and continued use in higher-risk disease, challenging reliance on long-term endocrine therapy in all ER+ patients amid its toxicities and supporting prospective trials (e.g., maturing EUROPA) to evaluate ET omission in the ultra-hypofractionated RT/APBI era for select low-risk patients.
BACKGROUND:Standardized implant protocols have shown promise in improving outcomes in transcatheter aortic valve replacement (TAVR). However, the impact of implantation depth on clinical outcomes remains unclear. OBJECTIVES:The aim of this study was to evaluate clinical and hemodynamic outcomes across varying TAVR implantation depths using data from the Optimize PRO study. METHODS:This prospective, multicenter Optimize PRO study included patients with symptomatic severe aortic stenosis undergoing TAVR with Evolut PRO and Evolut PRO+ systems. Patients were stratified by core laboratory-adjudicated noncoronary cusp implantation depth. The echocardiographic outcome composite included no or trace paravalvular regurgitation, aortic mean gradient ≤ 10 mm Hg, and no prosthesis-patient mismatch at discharge. RESULTS:Patients (N = 603) were stratified by implantation depth: <1 mm (n = 88), 1 to ≤3 mm (n = 196), >3 to ≤5 mm (n = 170), and >5 mm (n = 149). Baseline characteristics were similar across implantation depth groups, except for a higher proportion of women for higher implantation depths. Higher implantation depths were associated with less resheathing and recapture (27.3% [24 of 88], 33.7% [66 of 196], 48.8% [83 of 170], and 51.7% [77 of 149]; P < 0.001) and shorter median hospital stay (1 day [Q1-Q3: 1-1 day], 1 day [Q1-Q3: 1-2 days], 2 days [Q1-Q3: 1-3 days], and 2 days [Q1-Q3: 1-4 days]; P < 0.001). Rates of valve migration (0%, 0.5% [95% CI: 0.1%-3.6%], 0.6% [95% CI: 0.1%-4.1%], and 1.3% [95% CI: 0.3%-5.3%]; P = 0.63) were low across implantation depth groups. The 1-year all-cause mortality or all-stroke rate was comparable across implantation depth groups (8.1% [95% CI: 3.9%-16.2%], 7.2% [95% CI: 4.3%-11.8%], 10.7% [95% CI: 6.9%-16.5%], and 12.5% [95% CI: 8.1%-19.2%]; P = 0.40). After 1 year, higher implantation depths were associated with lower rates of permanent pacemaker implantation (2.3% [95% CI: 0.6%-8.8%], 9.2% [95% CI: 5.9%-14.3%], 15.9% [95% CI: 11.2%-22.4%], and 20.3% [95% CI: 14.6%-%27.7]; P < 0.001). Rates of NYHA functional class I were numerically different across implantation depth groups but did not reach statistical significance (77.8% [56 of 72], 71.8% [130 of 181], 65.2% [101 of 155], and 67.7% [84 of 124]; P = 0.09 across all classes). In men, echocardiographic outcome composite rates were not statistically different across depth groups (58.6% [17 of 29], 50.6% [39 of 77], 43.8% [35 of 80], and 36.1% [26 of 72]; P = 0.14), although the exploratory trend test reached statistical significance (P = 0.02). CONCLUSIONS:Higher TAVR device implantation was associated with improved clinical outcomes with similar safety events, including valve migration, across depths. The long-term effect of this approach, including the ability to perform redo TAVR safely, will be further studied in the future. (Optimize PRO; NCT04091048).
Purpose/Objective(s) While recent data suggests partial breast irradiation (PBI) may be safe in high genomic risk patients compared to whole breast irradiation (WBI), outcomes with accelerated PBI (APBI) using HDR brachytherapy stratified by genomic risk remain understudied. We hypothesized that high genomic risk would not be associated with increased ipsilateral breast tumor recurrence (IBTR) after APBI using HDR brachytherapy. The primary objective was to compare the cumulative incidence of IBTR between high- and low-genomic-risk groups in patients treated uniformly with APBI. Materials/Methods We analyzed 171 patients with early-stage, ER positive, HER2 negative invasive breast cancer treated from 2010–2022 with lumpectomy, sentinel lymph node biopsy, and APBI using HDR brachytherapy (34 Gy in 10 twice-daily fractions) at one institution who had available genomic testing (Oncotype DX or MammaPrint). High genomic risk was defined as Oncotype DX >25 or high-risk MammaPrint (n=63). Patient, tumor, and treatment characteristics were abstracted from the electronic medical record. Outcomes, including IBTR, regional recurrence (RR), contralateral breast tumor recurrence (CBTR), distant recurrence (DR), any recurrence (AR), and overall survival (OS) were estimated with Kaplan-Meier analysis. Results Median follow-up was 88.6 months (range 10.7–189). The median age at the time of PBI was 64 years (range 49-88). Most patients were postmenopausal (n=160). Most tumors were grade 1-2 (N=123) invasive ductal carcinoma (N=152). Adjuvant endocrine therapy was initiated by 161 patients (94%; 58 high-risk, 103 low-risk), and chemotherapy by 41 patients (24%; 39/62 assessable high-risk). There were 18 IBTR events overall (6 in high-risk, 12 in low-risk). Five-year IBTR, RR, CBTR, DR, AR, and OS were 3.8%, 2.0%, 0%, 1.2%, 5.2%, and 4.0%, respectively. High genomic risk patients did not have higher IBTR (5 year 5.2% vs 3.0%, 10 year 10.9% vs 16.9%, p=0.698), RR (5 year 3.9% vs 0%, 10 year 6.6% vs 0.9%, p=0.09), CBTR (5 year 0% vs 0%, 10 year 0% vs 3.3%, p=0.597), DR (5 year 0% vs 1.9%, 10 year 2.7% vs 1.9%, p=0.956), or AR (5 year 7.4% vs 3.9%, 10 year 13.1% vs 19.9 %, p=0.77). Conclusion In this large cohort with long-term follow-up treated uniformly with HDR brachytherapy APBI, there were no statistically significant differences in IBTR or other recurrence rates between high- and low-genomic-risk groups. These findings support the oncologic safety of APBI in carefully selected patients with high genomic risk.
