Consecutive Pts Research Articles

Prognostic value of exercise right ventricular-pulmonary arterial coupling in primary mitral regurgitation

Abstract Background Exercise-induced pulmonary hypertension (mPAP/CO slope >3mmHg/L/min) was recently associated with worse outcome in >moderate PMR. However, the prognostic value of right ventricle to pulmonary artery coupling (RVPAc) is unknown. Purpose Assess the prognostic value of RVPAc; determine the additional value of exercise over rest RVPAc and compare these findings to the mPAP/CO slope. Methods Cohort study including consecutive pts submitted to CPET-echo with >moderate PMR, no/discordant symptoms, preserved LV function and without >moderate concomitant valvular disease or atrial fibrillation (AF). Thorough assessment of RV systolic function and RVPAc (TAPSE/sPAP ratio) was obtained by echocardiography using a dedicated RV window. mPAP and CO were obtained by Doppler echocardiography. Primary outcome was the composite of all-cause mortality, cardiovascular hospitalization (CVH), new-onset AF and valvular intervention; secondary outcome was the composite of CVH and new-onset AF. Results A total of 128 consecutive pts (64±11 years, 61% men) underwent CPET-echo. Event-free survival rate was 55% and 46% at 1 and 2 years. Pts that reached the primary combined endpoint were significantly older, had larger left atrium indexed volumes (LAVi), higher proportion of grade 4 MR, lower absolute and normalized peak VO2, and a significantly higher mPAP/CO slope (2,1±0,8 vs.3,7±2,6). They had a significantly lower rest and exercise TAPSE/sPAP, RV global and free wall longitudinal strain, rest and exercise TAPSE and exercise RV free wall S’. Rest and low exercise TAPSE/sPAP scored the highest accuracy in predicting the primary combined endpoint among variables statistically significant in the univariate analysis and therefore were used in the multivariate model. Sequentially adding rest and low exercise TAPSE/sPAP significantly improved the baseline predictive model (age, LAVi and MR grade). Low exercise TAPSE/sPAP and LAVi remained as significant independent variables in the multivariate model. They also correlated with new-onset AF and CVH; with rest and low exercise TAPSE/sPAP constituting significant steps (Fig 2). Replacing low exercise TAPSE/sPAP for mPAP/CO slope in the proposed model only slightly improved its accuracy in predicting the primary and secondary composite outcomes. Adding predicted peak VO2 (≥80% vs <80%) did not significantly improve the accuracy of any of the multivariate models. Low exercise TAPSE/sPAP and mPAP/CO slope both correlated well with peak VO2 and VE/VCO2 slope. Conclusion Decreased rest or exercise TAPSE/sPAP are single point measures of RVPAc, associated with adverse outcome in pts with >moderate PMR and no/discordant symptoms. Low exercise TAPSE/sPAP has independent additional value over rest TAPSE/sPAP in predicting adverse events, with a similar accuracy as mPAP/CO slope. Low exercise TAPSE/sPAP is a potential alternative to mPAP/CO slope in this population and it may be simpler to adopt in clinical practice.Central Illustration

TAVI for treating severe aortic valve disease in cardiogenic shock: a single centre experience

Abstract Introduction Recent evidence shows the safety and efficacy of TAVI in patients with aortic valve disease (AVD) presenting in cardiogenic shock (CS). However, there is limited data regarding CS management in the cardiac intensive care unit (CICU) and its outcomes. We aimed to describe the CS features, pre-TAVI management and short-term clinical outcomes of a cohort of CS patients (pts) submitted to TAVI. Methods Single-centre retrospective registry of consecutive pts with AVD undergoing TAVI in CS, from January 2020 to October 2023. CS was defined as pre-procedural hypotension/hypoperfusion requiring vasoactive drugs or mechanical circulatory support (MCS) devices. The severity of CS was defined according to the SCAI classification. Procedural related outcomes according to the VARC-3 criteria and 30-day mortality were assessed. Results A total of 16 pts (1% of our global TAVI cohort, 62% male, mean age 79±5 years) meet the inclusion criteria. The majority (n=13) presented severe aortic stenosis, two had degenerated aortic bioprosthesis with severe regurgitation and one had native valve severe regurgitation. 6 pts (38%) had isolated left ventricle (LV) dysfunction and 10 (62%) had biventricular dysfunction. The admission LVEF was 33±8% and the mean transaortic gradient for those with aortic stenosis was 46±13mmHg. The EuroSCORE II estimated for a single non-CABG emergency procedure was 37±15%. All patients were refused for surgical treatment upon Heart Team discussion. At admission, 12 (75%) patients presented in CS SCAI-C, 1 (6%) in SCAI-D and 3 (19%) in SCAI-E. These last 3 patients presented in cardiac arrest upon admission to the CICU (time to ROSC from 2 to 15 minutes). The peak lactate level at 48 hours was 3.4 mmol/L [2.1-5.1] and the highest Vasoactive-Inotropic Score (VIS) during admission was 21 [11-45]. None of the patients needed MCS pre-TAVI. 5 (31%) patients required invasive mechanical ventilation and 5 (31%) renal replacement therapy. Median time between CICU admission and transfemoral TAVI was 2.5 days [IQR 1-7]. Procedural success was 100%, with 57% receiving a balloon-expandable and 43% a self-expandable valve. Post-TAVI CICU length of stay was 6 days [IQR 5-9]. Most common procedural complication were the need for permanent pacemaker implantation (n=2, 12%) and access-related bleeding (n=2, 12%). Hospital length-of-stay was 20±15 days. Thirty-day mortality was 12% (n=2). Conclusion In this cohort of CS patients selected for TAVI treatment, procedural success was achieved in all cases. While complications were similar to the general TAVI population, in-hospital mortality remained high but very acceptable. These results suggest that, if correctly selected, aortic valve disease patients in CS represent a niche for whom brief stabilization and urgent percutaneous valve treatment might impact their dismal prognosis.

Weight change does not impact long-term outcomes following cryoballoon pulmonary vein isolation

Abstract Background Weight loss has been suggested to reduce frequency and burden of atrial fibrillation (AF) in overweight patients (pts). However, there are limited data on weight loss impact on outcomes in pts with AF who have undergone pulmonary vein isolation (PVI). Purpose To understand the impact of weight change on long-term outcomes, as assessed by freedom from recurrent AF in pts undergoing cryoballoon (CB) PVI. Methods We enrolled consecutive pts with AF who underwent CB PVI; all had implantable loop recorders (ILR) for long-term ECG monitoring. The cohort was divided into 4 groups based on weight change 1-year post ablation: (1) optimal weight loss (OWL) – weight decrease ≥ 10%; (2) minimal weight loss (MWL) - weight loss (WL) 3-9% weight decrease; (3) no weight change (NWC) - weight change < 3%, (4) weight gain (WG) ≥ 3% weight increase. We assessed for AF recurrence after excluding a 3-month post-ablation blanking period. Results Out of a total of 322 pts who underwent ablation, 241 (75%) pts (69 ± 10 years; 159 (66%) male; 133 (55%) PAF; CHA2DS2-VASc 2.7 ± 1.5; BMI 30 ± 5) had weight information available at ablation and last follow-up. All were off antiarrhythmics by 1 year. There were no differences in the 4 cohorts with respect to baseline characteristics. During the first year, about ¼ of pts were able to lose ≥ 3% of weight but only 8 pts (3%) were able to lose ≥ 10%. AF recurred in 153 (63%); they were older, more likely to have persistent AF (PeAF), and a higher CHA2DS2-VASc score. However, weight change did not impact outcome (Figure). In a multivariate Cox Regression hazards analysis, PAF vs. PeAF at ablation was the only factor associated with any recurrence at follow-up (Figure). Conclusions Post CB PVI only about ¼ of pts are able to lose weight. Weight changes in the first-year post ablation in obese pts did not alter outcomes with respect to likelihood of recurrent AF. These data should be taken into account when considering catheter ablation.

Advanced mapping and ablation technologies to target pulmonary veins gaps and residual antral potentials during repeat paroxysmal AF ablation: acute and long-term follow-up

Abstract Background A comprehensive understanding of pulmonary vein (PV) reconnection and residual potentials (RAP) within the antral scar during repeat atrial fibrillation (AF) ablation, facilitated by advanced mapping and ablation technologies, is currently lacking. Optimizing radiofrequency (RF) deliveries after failed PV isolation (PVI) may enhance ablation efficiency. Purpose This study aims to assess both the acute and long-term outcomes focusing on PV gaps (PVGs) and RAPs, utilizing advanced mapping and ablation technologies during repeat PV ablation in patients (pts) with paroxysmal AF. Methods Repeat AF-CHARISMA study, a prospective, single-arm cohort study, included consecutive pts from 13 centers undergoing repeat ablation of paroxysmal AF. The Lumipoint (Boston Scientific) map-analysis tool was used sequentially on each PV component. All patients were followed-up for at least 12 months after the procedure. The ablation endpoint was PVI and electrical quiescence in the antral region. Long-term outcome was the recurrence of AT/AF over follow-up. Results One-hundred pts were included (69% after failed RF procedure, 31% after failed cryoablation procedure). A total of 276 PVGs (192 after RF ablation, 2.8±1.8/pt; 84 after cryoablation, 2.7±1.9/pt, p=0.665 vs RF) and 44 RAPs (43 after RF ablation, 0.6±1.1/pt; 1 after cryoablation, 0.03±0.2/pt, p=0.002 vs RF) were detected. In the majority of cases (75%), only PVGs were present whereas, in 21%, both PVGs and RAPs were detected (2 pts had only RAPs). In 2 pts no PVG nor RAP were identified. PVGs were most common at anterior sites (103, 37.3%), followed by posterior sites (75, 27.2%) and carina sites (49, 17.8%). PVG location sites did not differ between prior ablation approach. Only 1 pt after cryoablation showed a RAP (at carina site), whereas the 44 RAPs after RF were fairly distributed across different sites. Acute procedural success was 100%, with all PVs successfully isolated and RAPs completely abolished in all study pts. After the blanking period, over a follow-up of 480±211 days, 18 pts (18%) suffered an AT/AF recurrence (time to recurrence: 245±80 days). Previous ablation approach (HR=0.66, 95%CI: 0.2 to 2.0 for previous cryoablation, p=0.46), number of PVGs (1.05, 0.8 to 1.3, p=0.67) or number of RAPs (0.41, 0.1 to 1.2, p=0.12) were not associated to AT/AF recurrence. No major complications or adverse events occurred. Conclusion A structured ablation workflow for repeat catheter ablation, incorporating consistent high-density mapping and improved diagnostic tools to guide the procedure, demonstrated safety and efficacy in treating paroxysmal AF irrespectively of previous ablation approach. Residual potentials within the antral scar were more frequently detected after RF ablation compared to cryoablation.

High density mapping accuracy and efficiency in atrial fibrillation: real-world outcomes from the SECURE registry

Abstract Background/Introduction A high-density (HD) mapping catheter is valuable for validating pulmonary vein isolation (PVI) and analysing arrhythmic substrates of the left atrium (LA) during atrial fibrillation (AF) ablation. Multiple HD mapping catheters are available for use in clinical practice. A novel octa-spline mapping catheter with a close internal unipolar reference electrode is now available and may improve mapping efficiencies and image resolutions (Figure). Purpose This study aims to report real-world experiences with different commercially available HD mapping catheters in AF ablation and compare mapping performance. Methods SECURE is an ongoing observational, prospective, post-marketing study collecting real-world data on ablation procedures performed per standard-of-care. At the time of data extraction (Nov. 2023), 16 sites across 8 countries had enrolled 2,366 patients (pts), with 12-month follow-up data available for 828 pts. The current analysis, which included consecutive pts undergoing AF ablation, evaluated mapping efficiency and procedural outcomes with 3 HD mapping catheters: circular catheter (CC), penta-spline catheter (PSC), and octa-spline catheter (OSC). Mapping data were analysed with a cloud-based data management and artificial intelligence-powered algorithm. Results Overall, 859 pts with AF (paroxysmal AF [PAF], n=465; persistent AF [PsAF], n=240; long-standing PsAF [LS PsAF], n=154) were included in this analysis. The CC, PSC, and OSC were used in 428, 210, and 221 pts, respectively. Procedures using the OSC had a significantly higher mean mapping area (31,989.9 mm2) than those performed with the CC (23,152.2 mm2; P<0.0001) and PSC (29,804.6 mm2; P=0.0027), as well as a >3-fold higher mean mapping rate (138.4 vs 20.8 and 43.4 points/min, respectively; both P<0.0001). The higher number of mapping points translated to a higher mean mapping density (OSC, 0.34 vs CC, 0.05 and PSC, 0.07 points/mm2; both P<0.0001), with more uniform point distribution and less interpolation. With the CC, PSC, and OSC, respectively, total mean procedure times (incl PVI + other targets) were 118.0, 118.7, and 165.1 min, (P<0.0001 for OSC vs. both CC and PSC) and mean pre-ablation mapping times were 25.2, 25.0, and 21.5 min (P<0.0004 for OSC vs. both CC and PSC). The improved mapping quality and efficiency with the OSC allowed to include specific ablation targets beyond PVI. Fewer PVI-only procedures were performed with the OSC (29.4%) versus the CC (62.1%) and PSC (54.8%), while ablation of the PVI+ other targets was more common with the OSC versus the CC and PSC, including the cavotricuspid isthmus (37.1% vs 17.3% and 16.7%), LA roof (42.5% vs 13.1% and 21.4%), and LA posterior wall (21.7% vs 10.5% and 16.2%). Results were overall consistent per AF type (Table). Conclusions By providing more accurate mapping, the OSC allows for improved analysis of the arrhythmic substrate, which may improve ablation outcomes for pts with PAF and PsAF.Figure 1

Clinical History of Patients with Hypertrophic Cardiomyopathy-How to Improve the Initiation Process of the Diagnosis?

Background: Regardless of genetic origin and recommended screening methods, hypertrophic cardiomyopathy (HCM) is commonly diagnosed late in the advanced stages of the disease. The aim of this study was to analyse the case history of patients with HCM in order to obtain an initiation of the diagnostic process. Methods: This study was a retrospective, tertiary, single-centre cohort analysis of 85 consecutive pts with HCM (mean age at the time of HCM diagnosis: 51 ± 15 years; F/M: 42/43) who were hospitalized during the period from 1 January 2013 to 31 December 2022. Type of referral to the hospital, the reason for hospitalization as well as accompanying symptoms, comorbidities, and family history were analysed to obtain an initiation of the diagnostic process. The analysis was limited to hospitalizations in which the diagnosis of HCM was stated for the first time. Results: An analysis of the type of referral to the hospital revealed the following data: 18% of patients were admitted as urgent hospitalizations (UHs) and 82% as elective hospitalizations (EHs). Among the UHs, the majority of patients were transferred from another hospital (13%), and among the EHs, 65% of patients were referred from a specialised outpatient medical care (SMC) facility. The majority of patients in both the UH and EH groups were symptomatic: 84% in the EH group (the most common symptom was exertional dyspnea in 56% of pts) and 93% in the UH group (the most common symptom was syncope in 60% of pts). Among the analysed population, the most frequent comorbidities were systemic hypertension (51%), lipid metabolism disorders (38%) and obesity (23%). Conclusions: A diagnosis of HCM is often made at an advanced age in symptomatic patients, mainly during an EH. Nearly one-fifth of the Polish HCM population is diagnosed during a UH after a sudden event, which suggests the need for improvements in medical care in Poland.

Predicting CDK4/6 inhibitors outcomes in pts with HR+/HER2- metastatic breast cancer: A machine learning approach.

1074 Background: CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) are the current standard of care for pts with newly diagnosed HR+/HER2- metastatic breast cancer (MBC). Although multiple pivotal trials showed a robust benefit of CDK4/6i over ET alone in all the subgroups, there is a subset of pts with a suboptimal response that is difficult to characterize. To predict the benefit on first line CDK4/6i in pts with HR+/HER2- MBC, we created a machine-learning (ML) model based on clinico-pathological features (CPFs) at baseline. Methods: We identified 854 consecutive pts with HR+/HER2- MBC receiving CDK4/6i as 1st line therapy between 12/2013 and 10/2023 from our MSK translational database. OncoCast-MPM ML framework was used to stratify pts based on progression-free survival (PFS) on 1st line CDK4/6i. CPFs of interest were selected as input for the models. Pts with missing data in any of the key inputs were excluded and used as hold out set. We tested 4 algorithms (GBM, ENET, LASSO and SVM), and selected the only model that returned predictions when tested on the hold out dataset containing missing data. The Kaplan-Meier estimator and the log-rank test were used to assess differences in PFS, and Cox regression was used to measure hazard ratios (HR) between groups. Results: Overall, 651 out of 854 pts and 15 CPFs were used in models' creation. The median PFS of the cohort was 15.95 months (95%CI: 14.04-17.95). Of the 4 tested architectures, GBM was the selected architecture based on its ability to be tested on the holdout cohort containing missing data. GBM identified 3 risk groups: good-response risk group (N=279), with a median PFS of 23.8 months (95%CI: 19.6-29.9), intermediate-response risk group (N=231), with a median PFS of 14.7 (I95%CI: 12.2-16.9), and poor-response risk group (N=141), with a median PFS 7.4 (95%CI: 5.3,9.1). The HR between good-response and poor-response RGs was 2.55 (95%CI: 2.0,3.2) with a of p = 2.54e-14. The first 5 CPFs by importance, sorted by Garson algorithm score are: disease-free interval, liver involvement, age at metastatic disease, adjuvant treatment-free interval, and progesterone receptor status. No statistically significant differences were observed between the 3 risk groups identified in the train-validation and tested in the holdout cohort, in terms of median, 1yr, 3yr survival times, as well as in HR. Conclusions: ML-based models have the potential to identify subsets of pts likely to poorly respond to first line CDK4/6i leveraging clinico-pathological features. Risk stratification can help clinicians to select pts who may benefit from short-term interval imaging and potential cfDNA monitoring, as well as to identify the right population to design clinical trials with escalating treatment approaches.

Germline NQO1c.559C>T as a biomarker of genetic susceptibility to immune checkpoint blockade resistance.

8537 Background: Tobacco is the main risk factor for developing lung cancer. Yet, some heavy smokers do not develop cancer while others do at young ages. The study of cancer immunology has led to the surge of immune checkpoint blockade (ICB), which transformed the treatment landscape of cancer pts. NQO1 has been associated with extreme phenotypes of high risk for the development of tobacco-induced NSCLC and with poor survival outcomes for xerographs. Development of biomarkers for ICB has been mainly focused on tumor-related factors while genetic susceptibility of the host has been poorly explored to date and some evidence suggests that genetic dysregulation may enables immune escape. Methods: From June 2016 to January 2023, 326 NSCLC pts from two main University Hospitals of Malaga (Spain) receiving ICB were prospectively enrolled, blood samples were gathered. We selected a representative set of 60 consecutive pts for exome sequencing to characterize the germline contribution to resistance (progression within the first 6 months of treatment). PBMC DNA was extracted and prepared for exome sequencing. Raw sequencing data was processed and aligned to a reference genome using BWA. Base recalibration, germline variant calling and variant filtering was performed through GATK. Survival probabilities were estimated with the Kaplan-Meier method and compared using the log-rank test. We explored the lung cancer related genes among our results. Results: Median age at diagnosis of 64 (54-85). 76,6% were men. 44/60 (73,3%) were adenocarcinoma (ADC), PD-L1≥1% in 55% of patients, 22% shown PD-L≥50%. 78% had advanced disease at diagnosis. 65% received ICB in combination with chemotherapy. We found NQO1c.559C>T in 46,6% of pts (28/60). The variation was not associated with survival outcomes in the multivariant analysis (p>0.05) but with poor OS for non-ADC histology (19.7m vs 6m for mutated and WT, respectively; p<0.01). In addition, we found 26 germline variants associated with OS and PFS, and 52 variants with response to ICB. The variants were missense or involved a stop gain/loss. Conclusions: Exome sequencing analysis of germline variants could be a suitable methodology to identify subrogated biomarkers of immune resistance in NSCLC patients. NQO1c.559C>T might help to identify poor prognosis non-ADC pts in the ICB setting.

Primary localized malignant PEComa treated with surgery: A report of a large series of patients treated in a referral institution.

11582 Background: Perivascular Epithelioid Cell Tumors (PEComa) are mesenchymal neoplasms with a characteristic myomelanocytic immunophenotype. These tumors exhibit a broad anatomic distribution, and aggressive clinical behavior has been correlated with histological features such as tumor size and increasing mitotic activity. PEComas arising from the kidney are referred to as angiomyolipomas and usually lack metastatic potential, whereas epithelioid angiomyolipomas do have metastatic potential. Until now, only case reports or a limited number of patients have been documented in the literature, resulting in a lack of data regarding their clinical behavior. In this study, we present the outcomes of a large series of patients (pts) with primary localized malignant PEComa. Methods: This is a retrospective study involving all consecutive pts of any age affected by primary and localized malignant Pecoma surgically treated with curative intent at our institution from January 2000 to December 2023. Eligible pts had a pathologically confirmed diagnosis of malignant Pecoma. We present the outcome results in terms of Disease-Free Survival (that includes Local Recurrence (LR), Distant Metastases (DM), or death as first events) and Overall Survival (OS). Due to the low number of events only univariable analyses were performed. Results: 48 patients (19/48 M; 29/48 F) were identified. Median age at surgery was 50 yrs (range 18-80). Primary site was extremity and trunk in 19/48 pts, retroperitoneum in 13/48 pts and other in 16/48; median size of tumor was 11 cm (range 1-30 cm). At a m-FU of 57 mos (IQR:22-116), 8 pts died. Five- and 10-yr OS was 81.6% [95% Confidence Interval (CI): 70.1-94.9%)] and 77.3% (CI: 64.2-93.0%), respectively. One patient developed LR as first event, 9 developed DM and 3 died without any LR and DM; 3 and 1 patients developed DM as 2nd and 3rd event, respectively. Five- and 10-yr DFS was 69.4% [CI: 56.3-85.6%] and 65.1% (CI: 50.9-83.1%). Predictors of higher risk of DFS were age (>64 yrs old) and site of origin [p=0.5; HR trunk and arms: 1.2 (CI: 0.38-3.81) vs. retroperitoneum and 3.49 (CI: 0.43-28.37) vs other]. Conclusions: In this series PEComas have a 30% risk of recurrence at 5 years. While age and the site of origin are associated with the natural history of the disease, better pathologic criteria are needed to stratify their risk.

Impact of comorbidity on outcome and treatment choice in patients with head and neck squamous cell carcinoma (HNSCC).

e18033 Background: Most patients (pts) with HNSCC are elderly and suffer from other diseases that, similarly to cancer, are related to smoking and alcohol habit. Therefore, these pts often may present at diagnosis with both comorbidities and other primary tumour with which they share the same risk factors. Several studies have shown that in cancer pts, the presence of comorbidities is a strong negative prognostic factor that can predict worse survival and a factor involved in changing cancer treatment choices. The Charlson Comorbidity Index (CCI) is a known tool for assessing the comorbidity burden of pts, with broad and validated prognostic value in the HNSCC population. Methods: The aim of this study is to retrospectively analyze, in a single cohort of HNSCC pts, the role of comorbidity burden on treatment choice and pts outcome.Data from the medical records of pts treated at Spaziani Hospital, FR, Italy from May 2019 to Jan 2023 for an HNSCC were collected. All pts had received a variable combination of surgery, chemo and radiotherapy for their tumor. All pts were staged according to CCI and divided into four groups of comorbidity burden. Data on treatment choice (trimodal (variable combination of surgery+chemotherapy+radiotherapy) vs non-trimodal) were also recorded for stage III-IVA pts. Results: 54 consecutive pts were enrolled. The disease sites included the oral cavity (14 pts), oropharynx (18 pts), larynx (9 pts), nasal cavity/paranasal sinuses (6 pts), occult primary (4 pts) and hypopharynx (4 pts).Of the 54 pts the 22.2% and 77.8% were female and male, respectively. Most pts (39 pts, 72.2%) had stage III-IVA disease. 35 and 40 pts, respectively received a surgical and nonsurgical primary therapy. 13 pts received a trimodal approach. The median observed PFS was 22.4 months (95% CI: 12.6-32.2). No significant differences in DFS were observed according to age (<65 vs ≥ 65 years, p 0.99), sex (p 0.45), comorbidity burden (CCI 0, CCI 1-2, CCI 3-4, CCI≥5; p 0.99), RT (yes vs no, p 0.90), CT-RT (yes vs no, p 0.62), smoking (p0.91). In our cohort, only an ECOG Performance Status 0 (0 vs ≥1; p 0.028) and HPV status (pos vs neg; p 0.002) were correlated with a better DFS. A high comorbidity burden (CCI score) was present in >85% of pts. In general, those who undergo trimodal treatment among stage III-IV pts are those with PS 0 vs ≥ 1 (40% vs 23.5%), with age < 65 vs ≥65 years (40.0% vs 26.3%), with a CCI ≤1 vs CCI >1 (47.6% vs 16.7%), absence vs presence of CV morbidity (40.6% vs 0%), female vs male (50% vs 27.6%), in the HPV+ vs HPV- (100% vs 25%). Among these, the presence of CV comorbidities (p 0.039), CCI (p 0.041) and HPV (p 0.018) are statistically significant. Conclusions: Our analysis suggests that in pts with Stage III-IVA, the presence of a higher comorbidity burden and CV morbidity are capable of influencing the choice of a trimodal treatment. A broader test is necessary due to the small sample size considered.

Cisplatin and capecitabine as definitive chemoradiation for squamous cell carcinoma of the anal canal (SCCAC): A prospective cohort.

e15503 Background: SCCAC is a rare disease. The standard of care treatment with curative intent is chemoradiation (CRT) with mitomycin (MMC) or cisplatin (CDDP) plus infusional 5-Fluoracil (5-FU). Capecitabine may replace 5-FU in MMC doublet. However, MMC and infusional pumps are frequently unavailable in underdeveloped countries. CCDP and capecitabine are widely available, but there is no prospective data about the feasibility and efficacy of this combination in a definitive SCCAC CRT setting. Methods: A Prospective cohort study aimed to evaluate the safety and efficacy of treatment with chemoradiation with CDDP 60mg/m2 D1 and D29 plus Capecitabine 825mg/m2 BID in a population without MMC and infusional pump access. Eligible patients (pts) had T2-4, N0-3, and M0 disease candidates for a full curative CRT regimen. The study data were prospectively collected using REDCap. The primary endpoint was the response by RECIST v.1.1 at 24 weeks(w). The secondary endpoints included toxicity by CTCAE v.5.0, adherence, PFS, and OS. Results: We enrolled 40 consecutive pts between Aug/2019-Dec/2022 in a tertiary cancer center in Brazil. The median age was 61y, the majority were stage III (n = 31, 77.5%) and ECOG 1 (n = 20, 50%). HIV+ serology was observed in 11 pts (27,5%). All patients received CRT, with a median dose of 54Gy in the primary tumor and 45Gy in the elective nodes. At 8w, 35% (n = 14) had a complete response (CR), 50% (n = 20) partial response (PR), and 2.5% (n = 1) progressive disease (PD). At 6 months, CR was observed in 55% (n = 22), PR in 22.5% (n = 9), and PD in 10% (n = 4). 11 pts had disease recurrence, and six died. 1y OS was 94.7% (IC95%: 80.7- 98.6%), and 1y PFS was 75.3% (IC95%:57.8 - 86.3%). Colostomy-free survival at one year was 89.6% (IC95%: 74.7 - 95.9%). Median PFS and OS were not reached with a 2-year median follow-up. Regarding toxicities, radiodermatitis was observed in 94% (n = 36), nausea in 90% (n = 36), and diarrhea in 65% (n = 26). Any grade 3/4 toxicity was present in 27.5% (n = 11), being the majority of radiodermatitis. Four older pts (average age 73y) had definitive suspension of treatment due to toxicity, 06 pts were hospitalized because of a skin infection, and one died due to treatment toxicity. Conclusions: Definitive chemoradiotherapy with cisplatin and capecitabine is feasible; however, older populations require extra attention to early toxicities management.

Correlation between metastatic site and immunotherapy efficacy in patients with advanced dMMR/MSI colorectal cancer: Real-World Italian multicentric retrospective study (Colon-MSI).

e15544 Background: Immune checkpoint inhibitors (ICIs) are the gold standard therapy in metastatic colorectal cancer (mCRC) patients (pts) with microsatellite instability (MSI). The Colon-MSI study aimed to describe a cohort of MSI mCRC pts treated with ICIs before Italian pembrolizumab approval and to evaluate the efficacy, safety, and possible predictive factors of response in a real-world setting. Methods: We retrospectively collected data of pts with MSI mCRC treated with ICIs before June 30, 2023, in 16 Italian Cancer Centers. The OS was calculated from the diagnosis of metastatic disease, and the PFS from the beginning of ICIs. We explored the correlation between clinicopathological factors, survival outcomes, and treatment response. Results: Between January 2021 and June 2023, we reported 83 consecutive pts with data available. Among all, the median age was 61 years (23-86), 42 (51%) were female, and 45 (54%) had a ECOG PS 0; 35 (42%) pts were at stage IV at diagnosis, and 61 (74%) had right colon tumor site. The most common metastatic sites were liver (35%), lymph nodes (43%), peritoneum (31%), and lung (15%); 48 (58%) pts had a single metastatic site. 33 (39%) pts had a mucinous adenocarcinoma, 32 (39%) BRAF mutated, 32 (39%) RAS mutated, and 26% presented a Lynch syndrome. The majority of pts (69%) were pre-treated, and 26 pts (31%) received ICIs in first line. Nivolumab alone or plus Ipilimumab, and Pembrolizumab, were administered in 23 (28%), 3 (4%), and 57 (68%) pts, respectively. The median follow-up was 23 (1-65) months (m) and the median duration of treatment was 23 m (0-65) with 27 pts still ongoing. Treatment-related severe toxicities (G3 or G4) were observed only in 5.6% of pts. The median OS and PFS were not reached; the mean OS was 45.6 m (IC 95% 39.6-51.6) and the mean PFS was 38.8 m (IC 95% 32.5-45.1). Complete response (CR) was observed in 20 pts (24%), partial response (PR) in 28 (34%), stable disease (SD) in 19 (23%) and progression disease (PD) in 16 (19%). Overall response (ORR) was observed in 48 pts (57.8%; 95 %IC 0.31- 0.53), and disease control rate in 67 pts (80.7%; 95% IC 0.11– 0.29). Lung metastatic site was associated with poorer outcome in terms of OS (p = 0.001, HR 3.88 IC 95% 1.7-8.9), PFS (p = 0.045 HR = 2.31 IC95% 1-5.2), and ORR (p = 0.015 OR = 6.19 IC95% 1.4-26.9). Significantly worse PFS was also observed in pts with liver metastasis (p = 0.009 HR = 2.5 IC 95% 1.3-4.9). Conclusions: Our data confirm that ICIs are effective and well-tolerated treatment in MSI mCRC pts, with long-term clinical outcomes reported. These results suggest an unfavorable correlation between lung and liver metastasis and the ICI response. Further biomolecular analysis will be provided in the future.

TACE combined with tislelizumab and lenvatinib in the treatment of advanced liver cancer: A real world study.

e16270 Background: The combination of transcatheter arterial chemoembolization (TACE) plus Lenvatinib prolonged progression-free survival (PFS) and overall survival (OS) than Lenvatinib or TACE monotherapy for patients with hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of Lenvatinib plus monoclonal antibody against programmed cell death 1 (anti-PD1) and TACE for patients with advanced HCC. Methods: Pts with advanced HCC who treated with Lenvatinib plus anti-PD1 and TACE were enrolled. Objective response rate (ORR), PFS, disease control rate (DCR) and OS were calculated to assess the antitumor response and the treatment-related adverse events to the safety. Consecutive pts were identified from September 2021 to August 2023.The Patients were included based on the following chief eligibility criteria. After signing the informed consent form, patients received sequential treatment with TACE in combination with Lenvatinib and tislelizumab. The anti-PD1 were recommended to be used continually every 3 weeks until disease progression, or intolerable toxicity. Lenvatinib was recommended to be used continually every day until disease progression, or intolerable toxicity. Follow up TACE should be given according to the patient's condition, no more than 3 times. Results: Between Sep. 2021 to Aug. 2023, 45 were enrolled. All pts received at least one dose of study treatment. The median age was 56 years(range34,73), 4 of the pts are BCLC-B stage, 41 of the pts are BCLC-C stage.Progression occurred in 8 of 45 patients and 14 patients died. The median PFS was 13.4 months (95% CI: 10.9-15.8 months) and the median OS was 20 months (95% CI: 9.8-30.4months). Of the 45 patients, a total of 3 (6.7%) patients achieved complete response (CR), and these 3 patients were treated with surgical resection. Partial Response (PR) was achieved in 12 patients (20%), Stable Disease (SD) in 22 pts (33.3%), Progressive Disease (PD) in 8 pts (17.8%), and Objective Response Rate (ORR) in patients. The Objective Response Rate (ORR) was 33.3% and the Disease Control Rate (DCR) was 82.2%.Treatment-related adverse events included increased AST 44.4%(20/45), increased ALT 51.1%(23), increased total bilirubin 42.2%(19/45), rash 44.4%(20/45), pruritus 42.2%(19/45), gastrointestinal reaction 33.3%(15/45), abdominal pain 24.4%(11/45), sensory abnormality 20%(9/45), and arthralgias 4.4%(2/45), etc., and Grade 3 Adverse events were increased ALT 2.2%(1/45), increased AST 4.4%(2/45), increased total bilirubin 2.2%(1/45), rash 2.2%(1/45), and gastrointestinal reaction 2.2%(1/45).No grade 4 or above adverse events occurred. Conclusions: In this study, TACE plus anti-PD1 and targeted therapies showed favorable efficacy and manageability in patients with advanced HCC. Toxicity was manageable with a low incidence of grade 3-4 adverse events. There were no unexpected safety signals.

Clinical validation of a prognostic 7-marker IHC assay (7-IHC) in 382 patients (pts) with stage IB/IIA cutaneous melanoma (CM; MELARISK-001).

9572 Background: For pts with resected CM, adjuvant anti-PD1 is approved for AJCC v8 stage IIB–IV and BRAFi/MEKi for stage III–IV disease. Nonetheless, there remains a subgroup of pts within stages IB/IIA, which is at high risk of relapse and death, accounts for a considerable share of overall CM mortality (1), and lacks access to such therapy. Thus, adjuvant clinical trials in this “early”-stage setting may be merited. However, this subgroup is not detectable via AJCC staging alone. A prognostic 7-IHC assay that was developed (2), and analytically (3) and prospectively clinically validated (4) to identify stage IB/IIA pts at high risk of relapse and death, may be useful in selecting pts for adjuvant trials (2,4). Here, we report results from the MELARISK-001 multicenter study of that assay. Methods: MELARISK-001 enrolled consecutive pts diagnosed with stage IB/IIA CM from 2000–16, with available formalin-fixed paraffin-embedded primary melanoma. Specimens were analyzed by 7-IHC and pts classified as either high-risk or low-risk. Kaplan-Meier survival analysis and multivariate Cox regression analysis (MVA) against Breslow thickness, ulceration, age, and sex were performed. Results: MELARISK-001 included 382 pts; 247 (65%) pts in stage IB, 135 (35%) in stage IIA, all sentinel node-negative. Median Breslow thickness was 1.6 mm, median age 60Y. 212 pts (55%) were classified as 7-IHC high-risk, 170 pts (45%) as 7-IHC low-risk. Median follow-up for recurrence-free survival (RFS) was 90 mos, for melanoma-specific survival (MSS) 98 mos. Comparing 7-IHC high-risk vs low-risk pts, 5Y RFS was 79% vs 100%, 10Y RFS, 72% vs 99%, 5Y MSS, 92% vs 100%, and 10Y MSS 82% vs 100% (Table; logrank p<0.001). In MVA, 7-IHC risk class (hazard ratio [HR] 22.3; 95% CI 7.0–70.9), Breslow thickness (1.5; 1.1–1.9), and age (1.61; 1.0–2.5) were significant independent prognosticators of RFS. 7-IHC HR for MSS could not be computed due to 7-IHC's 100% sensitivity. Prognostic performance variables (95% CI) for RFS were: sensitivity 98% (91%–100%), positive predictive value 26% (20%–33%), negative predictive value 99% (97%–100%). Conclusions: 7-IHC risk categorization identified 98% of relapses and 100% of CM-related deaths in stage IB/IIA pts. In MVA, 7-IHC risk class was the strongest independent prognosticator of survival endpoints. 7-IHC high-risk pts have a relapse rate comparable to that of later-stage pts for whom adjuvant therapy is approved. MELARISK-001 provides further evidence supporting use of 7-IHC to identify early-stage pts at high risk of relapse and death who may benefit from adjuvant therapy trials. 1. Whiteman et al J Invest Dermatol 2015. 2. Meyer et al PloS ONE 2012. 3. Ziemer et al Diagnostics2023. 4. Meyer et al Eur J Cancer 2023. [Table: see text]

Preprocedural substrate assessment with computed tomography as an adjunct to endocardial voltage mapping for ablation of ventricular tachycardia: feasibility, procedural data and outcomes

Abstract Background Catheter ablation is an established therapy for ventricular tachycardia (VT) with endocardial voltage map (EVM) being the standard tool to characterize proarrhythmic substrate. However, this method is limited in certain ways, especially as intramural or epicardial substrate is not detected. In this context, multi-detector computed tomography (MDCT) has emerged as a promising alternative to cardiac MRI for preprocedural substrate assessment. Purpose Data regarding MDCT- guided VT ablation is scarce, especially in the context of late iodine enhancement MDCT. Present study sought to assess procedural parameters, safety, and efficacy of MDCT-guided VT ablation in direct comparison with a conventional VT ablation approach and is, to the best of our knowledge, the first systematic evaluation of clinical routine use of MDCT for preprocedural substrate assessment. Methods All patients (pts) undergoing VT ablation between January 2022 and August 2023 were included in this single-center registry. For MDCT-guided VT the CT images were uploaded to an online platform and processed using a dedicated software. Procedural parameters of MDCT-guided procedures were compared with the conventional EVM approach, and the study endpoint was a composite of death from any cause, heart failure hospitalization, and recurrence of VT. Results A total of 70 consecutive pts (age 62±13 y, 83% male) was included, of those 27/70 pts (39%) undergoing MDCT-guided and 43/70 pts (61 %) conventional VT ablation. An additional EVM was acquired in all MDCT pts. Baseline characteristics were similar. At comparable procedure durations (MDCT: 217±74 min, EVM: 194±57 min, p=0.15) the MDCT group showed a trend towards shorter mapping times (MDCT: 42±18 min, EVM: 49±13 min, p=0.09), particularly in cases with non-ischemic cardiomyopathy (NICM) (MDCT: 41±20 min, EVM: 54±15 min, p=0.07). An epicardial access was obtained in 8/23 pts (30 %) in the MDCT group and in 6/47 pts (14 %) in the EVM group (p=0.13). Bipolar ablation due to intramural scar detected by MDCT was performed in 3/27 pts (11 %) and in none in the EVM group. There was no difference in manifestation of acute kidney injury (MDCT: 3/17 pts (18 %) vs. EVM: 4/24 pts (21 %), p=1.0). After a median follow-up of 116 days (IQR 80-260 days), the study endpoint occurred in 8/17 (47 %) pts after MDCT-guided and in 14/31 pts (45 %) after conventional VT ablation. In one patient in the MDCT group a relevant coronary artery stenosis with urgent revascularization occurred immediately after bipolar ablation at the LV summit. No other complications were observed. Conclusion MDCT-guided VT ablation is safe and feasible with no differences in contrast agent-induced kidney injuries. Preprocedural CT substrate assessment identified complex intramural and epicardial scar, leading to bipolar and epicardial ablation. Mapping times trended shorter in the MDCT group, particularly in non-ischemic cardiomyopathy cases.

Mid-term outcomes after stereotactic arrhythmia radioablation for refractory ventricular tachycardia

Abstract Introduction stereotactic arrhythmia radioablation (STAR) is used as a rescue treatment for refractory ventricular tachycardia (VT) originating from unreachable myocardial substrate following unsuccessful radiofrequency catheter ablation (RFCA). The mid-term outcomes of STAR, however, remain poorly known. Objective to report the mid-term efficacy and safety outcomes in our series of 21 patients (pts) treated by STAR over 6 years. Methods Inclusion of consecutive pts treated by STAR with a Cyberknife system between 2017 and 2023. 3D-electroanatomical maps (EAM) of the VT substrate during unsuccessful RFCA were used to delineate the planned target volumes (PTV) on a 4D CT scan. Patients were followed up at least every 6 months by echocardiography and ICD interrogation at the outpatient clinic. Results 21 pts [16 (76 %) male, age 66±8 years] with a mean LVEF of 40±15% were included. The underlying substrate was ischemic in 7 (33 %); non-ischemic dilated in 7 (33 %); inflammatory in 4 (19%); hypertrophic in 1 (5%); neoplasic in 1 (5%); and malignant mitral valve prolapse in 1 (5%). A dose of 21±2 Gray was delivered to the PTV (26 ml, IQR 18-43 ml). After a median follow-up of 39 [IQR, 14-48] months, 12 pts (57%) remained in stable condition, 1 (5%) underwent a heart transplantation, 1 (5%) a left ventricular assistance device, 1 (5%) was in an incessant slow VT and 6 (29%) pts died (3 from end stage heart failure). 15 (71%) pts presented VT recurrences [7 (33%) ATPs; 3 (14%) shocks; 4 (19%) VT storm and 1 (5%) with a well-tolerated slow VT (100 bpm) with an LVAD till transplantation, of whom 9 (43%) required redo RFCA. The median value of total ventricular arrhythmic burden (defined as any arrhythmia requiring ICD therapies) decreased significantly from 31 (IQR, 4-100) to 7 (IQR, 1-23) (p<0.05); for nsVT from 57 (IQR, 1.5- 1196) to 41 (IQR, 0.5-584) (p ns); or ICD shocks from 1.5 (IQR, 0-5.5) to 0 (IQR, 0-2) (p<0.05); for ATPs from 21 (IQR, 2.5-94) to 4 (IQR, 0.5-13) (p<0.05). Figure 1 shows a graphic representation of arrhythmic burden before and after STAR. Conclusion in this cohort of highly selected pts with refractory VT, STAR significantly reduced the arrhythmic burden by a factor of 4 over a 3-year follow-up. Death rate remained high (29%), mostly by terminal heart failure. Nevertheless, a high proportion of pts had VT recurrences that were successfully managed by redo RFCA.VT burden before and after STAR

Use of cardiac MRI and wearable defibrillator to identify patients at low risk for arrhythmic events: single center experience

Abstract Introduction In our Center, patients (pts) with newly diagnosed HF and reduced LVEF underwent MRI to determine the presence and extension of delayed enhancement (DE) or scar areas. These patients were discharged with a wearable cardioverter defibrillator (WCD) as monitoring and temporary antiarrhythmic therapy until a three-month follow-up (FU). Subsequent FU was performed at 6 and 12 months. Methods From May 2016 to July 2023, 120 consecutive pts (97 M; mean age 65.3y±9.7y) with reduced EF (28.5%±8.5%) on OMT, were discharged with WCD and included in clinical FU. Coronary anatomy was acquired in 119 pts: absence of coronary atherosclerosis (ats) (44 pts); not significant ats(39 pts); Significant ats(36 pts). 1 pt did not perform angiography due to thyrotoxicosis. MRI was performed in 95 pts (EDV 181.9 ± 48.7 ml/m2; Mass 96.9± 23.4 g/m2, LVEF MRI 26.8% ±9.2). FU was performed at 3 months in all patients; at 6 months in 111pts and at 12 months in 107pts. WCD is still present in 4 pts. LGE score was used to quantify myocardial fibrosis by defining reduced extension as LGE score <5. Results MRI identified 57 pts with a delayed enhancement(DE) midwall pattern and in 13 of these there was a regional ischemic pattern also; 27 pts with regional scar; 18 pts without DE. During follow-up, 87 patients (75%) recovered LVEF function at 3 months (LVEF 44.3±6.3%) and were no longer indicated for ICD. 29 pts were implanted with ICD (25%). These patients had higher absolute and indexed volumes on MRI (p 0.053; p 0.042) and a greater presence of ischemic pattern (p 0.05). The LGE score was low in 76 pts (<5). A low LGE score is linked to the recovery of LVEF (p 0.04). Patients who undergo ICD had greater DE extension (p 0.01). 1 pt with a high LGE score (36.6) refused ICD and underwent SCD at 6 months. In pts with LGE score <5, 1 major arrhythmic event occurred (1 SVT in pt with ICD). In pts with LGE score >5, 3 major events occurred (1 shock on VF, 1 ATP on SVT, 1 SCD). 1 pt with extensive anterior akinesia who refused MRI presented 1 shock on VF at 6 months. 1 pt with partial recovery of LVEF and extensive anterior akinesia refused MRI and presented cardiac arrest for VF at 6 months. Conclusions MRI has become essential for risk stratification in patients with reduced LVEF. It is useful for identifying pts with severe impairment LVEF and low risk of events. The absence of DE and/or the presence of a low LGE score are linked to a low risk of arrhythmic events at 6 and 12 months and to a higher probability of recovery LVEF regardless of the etiology. The volumetric dimensions found on MRI are inversely linked to the recovery of LVEF. The WCD represents additional safety with excellent compliance in pts who still do not have clear indications for a definitive ICD. The combined MRI and WCD strategy can help to reduce the need for definitive ICD and therefore healthcare costs. The size of the sample does not allow definitive conclusions.

Evaluation of the cavotricuspid isthmus contractile kinetics within an interventional CMR environment

Abstract Background Cavotricuspid isthmus (CTI)-dependent flutter is a common arrhythmia with recurrences following ablation up to 50%. Previous static morphological analysis have shown that CTI anatomical variability has an impact on ablation time and procedural success. However, whether the contractile kinetics of the CTI affect procedural success remains unknown to date. Purpose Assessment of the contractile kinetics of the CTI in a cardiac magnetic resonance (CMR) environment for patients (pts) referred for typical flutter ablation. Method 32 consecutive pts with typical right atrial (RA) flutter from our Heart Center were included in this study. RA wall contours during a single cardiac cycle were delineated on CMR 2D-images using the Tomtec software. CTIs were divided in 5 segments for detailed motion analysis as shown in the figure 1A. CTI length and displacement were measured both in caudo-cranial and postero-anterior directions. Quantification of the CTI kinetics was performed in Python by computing the 2D-Euclidean distance (between two extreme temporal positions of CTI points). Results The mean CTI length of the study population (mean age 66±10 years, 29 males) was 32±13 mm during RA systole and 49±15 mm during RA diastole, resulting in a mean CTI change of 17±7 mm over one cardiac cycle (maximum – minimum length). Figure 1A shows representative MRI views of the CTI during RA systole and diastole. Figure 1B shows examples of hypo- and hyperkinetics CTI from 2 representative pts. Figure 2C shows a gradual increase in segment displacement postero-anteriorly (8.1±7.3 vs 17.2±8.1 mm, p<0.05) and caudo-cranially (1.6±0.8 vs 4.5±2.4 mm) from the Eustachian valve toward the Tricuspid valve. Figure 2D indicates that the 2D-Euclidean displacement of the 5 segments varied between 8±7.7 mm and 18±8.5 mm depending on their location. Interestingly, the overall CTI displacement was 4.5 times greater forward than upward. Conclusion To our knowledge, this is the first study investigating the kinetics properties of the CTI in sinus rhythm of patients with typical RA flutter. The CTI showed displacements both in postero-anterior and caudo-cranial directions, with a gradual increase from the Eustachian to the Tricuspid valves. CTI displacement appeared highly variable across patients. Whether the kinetics of the CTI correlate with ablation success will be investigated shortly.

Influence of prior myocardial infarction on outcome in patients with ischaemic HFrEF: insights from the EVIdence based TreAtment in Heart Failure (EVITA-HF) registry.

There is scarce information about the influence of prior myocardial infarction (pMI) on outcomes in patients (pts) with ischaemic HFrEF. We analysed data from the EVIdence based TreAtment in Heart Failure (EVITA-HF) registry. EVITA-HF comprises web-based case report data on demography, diagnostic measures, adverse events and 1-year follow-up of patients hospitalized for chronic heart failure ≥ 3months (CHF) and an ejection fraction ≤ 40%. In the present study, we focused on the outcomes of pts with and without pMI in ischaemic HFrEF. Between February 2009 and November 2015, a total of 2075 consecutive pts with ischaemic HFrEF were included from 16 centres in Germany. A total of 81.2% were male, and the mean age was 71years. A total of 61.5% of the pts with ischaemic HFrEF had a history of pMI. These pts were treated less often with PCI (20.0 vs. 31.0%, p < 0.001) or CABG (3.8 vs. 7.7%, p < 0.001). They more often received an ICD (40.9 vs. 28.7%, p < 0.001), but less often a CRT-D (11.3 vs. 19.4%, p < 0.001). After multivariate adjustment, pts with pMI had a greater all-cause mortality after 1year than those without pMI (hazard ratio 1.4; 95% CI, 1.10-1.79, p = 0.007). The combined endpoint of death, resuscitation or ICD shock after 1year was greater in patients with pMI (20.8 vs. 16.4%, p = 0.03). Mobility was more often reduced in pts with pMI (46.8% vs. 40.1%, p = 0.03), and overall health status was more frequently worse in patients with pMI than in those 12months ago (23.1 vs. 15.9%, p = 0.01). More than a quarter of the pts with ischaemic HFrEF were anxious or depressive. pMI in patients with CHF and ischaemic HFrEF was associated with increased mortality, increased event rates, and worsened health status. Hence, the subgroup of pts with ischaemic HFrEF and pMI is at higher risk and deserves special attention.

Abstract PO3-05-02: Impact of hormone receptor expression level in HR+/HER2- metastatic breast cancer in the large French ESME cohort

Abstract Background: In patients (pts) with early breast cancer (BC), the level of expression of estrogen receptor (ER) evaluated by immunohistochemistry is prognostic and predictive while progesterone receptor (PR) expression has an additional prognostic value. Allred scoring combines the percentage of positive cells and the intensity of staining. It is widely used for treatment choice for early BC. In metastatic setting, its role is less defined. Methods: The ESME database is a French National cohort of all consecutive pts who initiated a first-line treatment for metastatic BC (MBC) between January 2008 and December 2020 in one of the 18 French Comprehensive Cancer Centers (NCT03275311). For this study, we selected pts with HER2- MBC, known ER expression and intensity percentages, known PR status and who received endocrine-based therapy as first-line metastatic treatment. Primary objective was to evaluate the overall survival (OS) and first line progression-free survival (PFS1) under endocrine therapy according to ER and PR expression level. ER expression was defined using Allred score on the last available tumor sample. PR status was defined using a positive (≥10%)vs negative ( &amp;lt; 10%) threshold. Secondary objective was to evaluate clinical PFS1 whether de novo or recurrent MBC and according to type of first line therapy (mono- vs combined endocrine therapy). Results: In the ER+ ± PR+/HER2- population, 8269 pts had information on ER percentage and staining intensity. Median follow-up was 53.4 months (95%CI [51.9; 54.7]). Allred score distribution, OS and PFS1 are described in table 1. Median OS was 43.1 months [41.1; 45.0] for the PR- group compared with 52.3 months [50.5; 54.4] for the PR+ group. After adjustments, patients with a PR- tumour had still a worse prognosis (HR=1.20, 95%CI [1.12-1.28], p&amp;lt;0.001). Median PFS1 was 10.2 months[9.6; 10.8]and 14.8 months[14.2; 15.4] for pts with PR- vs PR+ tumour (HR=1.36 (1.29-1.43), p&amp;lt;0.001) and PR status remained significant prognostic factor independently of de novo or recurrent status and association or not with a targeted therapy. Conclusion: ER expression evaluated using the Allred scoring, as well as PR positivity, retain prognostic value in first-line MBC patients. Table 1 : OS and PFS according to Allred status, de novo status and type of endocrine therapy. * Selected variables on multivariate model include PR status, age, SBR grade, histological subtype, number of metastatic site, type of metastasis (non visceral, visceral, brain visceral), HER 2 (0 vs 1-2), metastatic-free interval, mono- vs combined endocrine therapy. Citation Format: Marie Alexandre, Florence Castan, Thibault De La Motte Rouge, Audrey Mailliez, Etienne Brain, Thomas Bachelot, Monica Arnedos, Florence Dalenc, Jean-Marc Ferrero, Vincent Massard, Isabelle Desmoulins, Marie-Ange Mouret-Reynier, Christelle Levy, Anthony Gonçalves, Anca Berghian, Aude-marie Savoye, Jean-Sébastien frenel, Lise Bosquet, Suzette Delaloge, William Jacot. Impact of hormone receptor expression level in HR+/HER2- metastatic breast cancer in the large French ESME cohort [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 PO3-05-02.