Multicenter Retrospective Study Research Articles

Real-life effectiveness of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir.

Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is the recommended rescue therapy for patients with chronic hepatitis C infection who fail direct-acting antivirals (DAAs). Data are limited on the effectiveness of this treatment after the current first-line therapies. Our aim was to analyse the effectiveness and safety of SOF/VEL/VOX among patients failing sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). Retrospective multicentre study (26 Spanish hospitals), including chronic hepatitis C patients unsuccessfully treated with SOF/VEL or GLE/PIB, and retreated with SOF/VEL/VOX ± ribavirin for 12 weeks between December 2017 and December 2022. In total, 142 patients included: 100 (70.4%) had failed SOF/VEL and 42 (29.6%) GLE/PIB. Patients were mainly men (84.5%), White (93.9%), with hepatitis C virus genotype (GT) 3 (49.6%) and 47.2% had liver cirrhosis. Sustained virological response (SVR) was evaluated in 132 patients who completed SOF/VEL/VOX and were followed 12 weeks after end of treatment; 117 (88.6%) achieved SVR. There were no significant differences in SVR rates according to initial DAA treatment (SOF/VEL 87.9% vs. GLE/PIB 90.2%, p = 0.8), cirrhosis (no cirrhosis 90% vs. cirrhosis 87.1%, p = 0.6) or GT3 infection (non-GT3 91.9% vs. GT3 85.5%, p = 0.3). However, when considering the concurrent presence of SOF/VEL treatment, cirrhosis and GT3 infection, SVR rates dropped to 82.8%. Ribavirin was added in 8 (6%) patients, all achieved SVR. SOF/VEL/VOX is an effective rescue therapy for failures to SOF/VEL or GLE/PIB, with an SVR of 88.6%. Factors previously linked to lower SVR rates, such as GT3 infection, cirrhosis and first-line therapy with SOF/VEL were not associated with lower SVRs.

Abstract PO3-22-08: Impact of Zip Code-Based Income on Reconstructive Method and Outcomes in Mutation-Positive Breast Cancer Patients

Abstract Background: In the United States, 13% of women develop invasive breast cancer, with certain genetic mutations increasing the risk. Genetic screening is costly and burdensome for patients, particularly those from lower socioeconomic backgrounds. Moreover, lower income (LI) patients face barriers in accessing healthcare and have lower rates of breast reconstruction. This study aims to examine the impact of socioeconomic status, as indicated by ZIP code median income, on the type of breast surgery, reconstructive technique, and perioperative outcomes among mutation-positive (M+) patients. Methods: A multicenter retrospective cohort study included patients with a genetic predisposition for breast cancer and undergoing breast and reconstructive surgery between January 2016 and October 2022. Patient demographics, history, operative details, and postoperative outcomes were collected. Patient ZIP codes were cross-referenced with the American Community Survey to determine the median household income, which served as a proxy for the patient-specific household income. Four distinct income quartiles were established: quartile 1 (Q1) = $37,045-$81,586 (“LI”); quartile 2 (Q2) = $81,587-$103,703; quartile 3 (Q3) = $103,704-$129,768; and quartile 4 (Q4) = $129,769-$213,724. Results: Among the 170 patients analyzed, 42 (24.7%) were in Q1, 42 (24.7%) in Q2, 44 (25.9%) in Q3, and 42 (24.7%) in Q4. Most patients had BRCA1 (n=73, 42.9%), BRCA2 (n=68, 40.0%), PALB2 (n=11,6.5%), or CHEK2 (n=8, 64.7%) mutations, and underwent prophylactic mastectomy without evidence of breast cancer (n=119, 70.0%). Mean age and body mass index (BMI) were 41±16 years and 25.0±7.5 kg/m2, respectively. There was a significant association between patient race and income (p< 0.0001), such that 30.1% of White patients were in Q4 (vs. 8.3% of Black patients), compared to 38.9% of Black patients in Q1 (vs.19.0% of White patients). LI was significantly associated with higher BMI (p=0.0083) and obesity rates (p=0.0080). Nipple-sparing mastectomy (NSM) (n=103, 60.6%) was the most frequent surgical approach, followed by skin-sparing mastectomy (SSM) (n=42, 24.7%), simple mastectomy (n=13, 7.6%), lumpectomy (n=4, 2.4%), and radical mastectomy (n=4, 2.4%). Patients in Q3 underwent NSM significantly more often than those in Q1 (p=0.0080). Tissue expander (n=73, 42.9%) was the most common reconstruction method. 34.7% of patients (n=59) experienced postoperative complications. Short-term (< 30 days postoperatively) complications included delayed wound healing (n=22, 12.9%), surgical site infection (n=16, 9.4%), dehiscence (n=12, 7.1%), cellulitis (n=10, 5.9%), seroma (n=9, 5.3%) and hematoma (n=9, 4.7%). Long term (≥30 days postoperatively) complications included mastectomy flap necrosis (n=22, 12.9%), total reconstructive failure (n=8, 4.7%), and red breast syndrome (n=2, 1.2%). There was no significant association between income level and incidence of complications (p >0.05). Income level significantly correlated with cancer recurrence, as patients in Q2 (n=0, 0.0%) and Q4 (n=1, 2.4%) had significantly lower recurrence rates compared to Q1 (n=6, 14.3%) (p=0.0140). Of the 30.0% of patients with diagnosis of cancer at DOS, 66.7% (n=34) of patients had ductal carcinoma in situ (DCIS). Eleven of these patients were in Q1, five in Q2, six in Q3, and twelve in Q4 (p=0.259). Conclusion: LI M+ patients had lower NSM rates than higher income patients, despite similar rates of prophylactic mastectomies, possibly due to perceived costs of increased follow-up care. Moreover, LI patients experienced higher cancer recurrence, despite similar incidences of equivalent cancer subtypes at presentation, likely reflecting differences in post-diagnostic care and morbidity. These findings highlight the need to address financial barriers and ensure equitable access to comprehensive care for M+ patients of all income strata. Citation Format: Jaytin Gupta, Shrayus Sortur, Christian Lava, Margaret Lee, Lauren Berger, Varsha Harish, Daisy Spoer, Lindy Rosal, Ian Greenwalt, Lucy De La Cruz, David Song, Kenneth Fan. Impact of Zip Code-Based Income on Reconstructive Method and Outcomes in Mutation-Positive 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 PO3-22-08.

Effect of Novel Inflammatory Biomarkers on Adverse Outcomes in Patients with Interstitial Lung Disease and Pneumonia: A Multicenter Retrospective Cohort Study.

Interstitial lung disease frequently coincides with pneumonia in clinical settings, and both conditions are closely associated with immunoinflammation. The Systemic Immune Inflammatory Index (SII) is a recently identified marker, and its connection to the prognosis of individuals suffering from interstitial lung disease and concurrent pneumonia remains unclear. The objective of this study was to scrutinize the correlation between varying SII levels and unfavorable outcomes in patients grappling with interstitial lung disease complicated by pneumonia. This study encompassed a retrospective multicenter cohort of 324 patients diagnosed with interstitial lung disease and pneumonia, all receiving glucocorticoid treatment during their hospitalization. We initially conducted ROC analysis to determine the optimal SII threshold. Subsequently, we examined disparities in clinical symptoms, physical signs, clinical test data, and other clinical attributes among patients with differing SII levels. Later, we employed the Kaplan-Meier survival curve method to assess the association between distinct SII levels and the 30-day and 90-day mortality rates in patients dealing with interstitial lung disease complicated by pneumonia. Finally, a Cox regression model was employed to identify factors influencing adverse prognosis in these patients. The findings demonstrated that the optimal SII threshold for predicting 30-day mortality was 1416.97, with an AUC of 0.633 (95% CI: 0.559-0.708) and a P value of <0.001. For 90-day mortality, the optimal SII threshold was 994.59, yielding an AUC of 0.628 (95% CI: 0.56-0.697) and a P value of <0.001. Noteworthy statistical distinctions emerged in dyspnea, cyanosis, and oxygenation index among patients with varying SII levels. Additionally, invasive mechanical ventilation, non-invasive ventilation, and extended infection duration independently constituted 30-day and 90-day mortality risk factors. Elevated heart rate and higher SII levels emerged as independent risk factors for 90-day mortality. To some extent, SII levels exhibit correlations with the clinical manifestations in patients grappling with interstitial lung disease complicated by pneumonia. Notably, a high SII level is an independent predictor for an unfavorable prognosis in these patients. Nevertheless, these findings warrant further validation through prospective cohort studies.

Abstract PO5-23-06: Predictive Factors for Reconstructive Method and Outcomes in Mutation-Positive Breast Cancer Patients

Abstract Background: BRCA1 and BRCA2 mutations significantly increase the risk of breast cancer, and prophylactic mastectomy reduces the risk by around 90% in these patients. Previous studies have explored predictors of mastectomy type in high-risk genetic mutation patients, but further characterization is needed. This study aims to identify factors associated with resection and reconstruction methods and predictors of postoperative complications in mutation-positive (M+) patients. Methods: A multicenter retrospective cohort study included patients with a genetic predisposition for breast cancer undergoing breast surgery, seen between January 2016 and October 2022. Patient demographics, comorbidities, oncologic history, operative details, and postoperative outcomes were collected. Descriptive statistics and multivariate logistic regression were performed. Results: Among the 176 patients analyzed, 75 (42.6%) had BRCA1, 71 (40.3%) had BRCA2, 11 (6.3%) had PALB2, and 8 (4.5%) had CHEK2 mutations. Mean age and body mass index (BMI) were 41.0±17 years and 24.9±6.9 kg/m2, respectively. Among patients with prior breast reconstruction (n=86, 48.9%), augmentation mammoplasty (n=31, 17.6%) was the most common procedure, followed by oncologic resection (n=21, 11.9%) and reduction mammoplasty (n=15, 8.5%). Nipple-sparing mastectomy (NSM) (n=107, 60.8%) was the most frequent surgical approach, followed by skin-sparing mastectomy (SSM) (n=43, 24.4%), simple mastectomy (n=14, 8.0%), lumpectomy (n=4, 2.3%), and radical mastectomy (n=4, 2.3%). Tissue expander (n=77, 43.8%) was the most common reconstruction method. By a median follow-up duration of 23.9 months, 66 (37.5%) of patients experienced postsurgical complications. Operative complications recorded within 30 days included seroma (n=9, 5.1%), hematoma (n=8, 4.5%), cellulitis (n=10, 5.7%), dehiscence (n=13, 7.4%), surgical site infection (n=11, 6.3%), and delayed wound healing (DWH) (n=24, 13.6%). Other long-term complications included mastectomy flap necrosis (n=22, 12.5%), total reconstructive failure (n=9, 5.1%), red breast syndrome (n=2, 1.1%), and capsular contracture (n=12, 6.8%). The choice of autologous breast reconstruction was correlated with younger age (OR 0.81, 95% CI: 0.69-0.95, p = 0.012) and Hispanic or Latino race (OR 0.01, 95% CI: 0.001-0.25, p=0.007). BMI was significantly correlated with incidence of hematoma (OR 1.17, 95% CI: 1.02-1.33, p=0.024), DWH (OR=1.1, 95% CI: 1.01-1.20, p=0.030), and dehiscence (OR 1.25, 95% CI: 1.09-1.43, p=0.001). Choice of autologous reconstruction was positively correlated with DWH (OR 8.86, 95% CI: 2.25-34.86, p=0.002) and dehiscence (OR 18.24, 95% CI: 2.58-129.158, p=0.004). Conclusion: In this macroscopic study, the most common breast reconstruction method for M+ patients was tissue expander-based. However, only autologous reconstruction was found to have positive correlates, specifically younger age and Hispanic or Latino origin. Younger patients may pursue this method given less concern for short term complications, which are historically increased in autologous reconstruction. Minority distrust of foreign medical material implantation may play a role in Hispanic or Latino choice. Additionally, autologous reconstruction and BMI were associated with certain postoperative complications, particularly dehiscence, DWH, and hematoma, results consistent with general breast cancer surgery cohorts. This study helps better characterize the M+ population and contributes insight into the resection and reconstructive choice in this patient population. Citation Format: Shrayus Sortur, Jaytin Gupta, Christian Lava, Lauren Berger, Varsha Harish, Zoya Khan, Daisy Spoer, Lindy Rosal, Ian Greenwalt, Lucy De La Cruz, David Song, Kenneth Fan. Predictive Factors for Reconstructive Method and Outcomes in Mutation-Positive 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 PO5-23-06.

Prehospital anesthesia in postcardiac arrest patients: a multicenter retrospective cohort study

BackgroundCurrently, the data regarding the impact of prehospital postcardiac arrest anesthesia on target hemodynamic and ventilatory parameters of early postresuscitation care and recommendations on its implementation are rare. The present study examines the incidence and impact of prehospital postcardiac arrest anesthesia on hemodynamic and ventilatory target parameters of postresuscitation care.MethodsIn this multicentre observational study between 2019 and 2021 unconscious adult patients after out-of-hospital-cardiac arrest with the presence of a return-of-spontaneous circulation until hospital admission were included. Primary endpoint was the application of postarrest anesthesia. Secondary endpoints included the medication group used, predisposing factors to its implementation, and its influence on achieving target parameters of postresuscitation care (systolic blood pressure: ≥ 100 mmHg, etCO2:35–45 mmHg, SpO2: 94–98%) at hospital handover.ResultsDuring the study period 2,335 out-of-hospital resuscitations out of 391,305 prehospital emergency operations (incidence: 0.58%; 95% CI 0.54–0.63) were observed with a return of spontaneous circulation to hospital admission in 706 patients (30.7%; 95% CI 28.8–32.6; female: 34.3%; age:68.3 ± 14.2 years). Postcardiac arrest anesthesia was performed in 482 patients (68.3%; 95% CI 64.7–71.7) with application of hypnotics in 93.4% (n = 451), analgesics in 53.7% (n = 259) and relaxants in 45.6% (n = 220). Factors influencing postcardiac arrest sedation were emergency care by an anesthetist (odds ratio: 2.10; 95% CI 1.34–3.30; P < 0.001) and treatment-free interval ≤ 5 min (odds ratio: 1.59; 95% CI 1.01–2.49; P = 0.04). Although there was no evidence of the impact of performing postcardiac arrest anesthesia on achieving a systolic blood pressure ≥ 100 mmHg at the end of operation (odds ratio: 1.14; 95% CI 0.78–1.68; P = 0.48), patients with postcardiac arrest anesthesia were significantly more likely to achieve the recommended ventilation (odds ratio: 1.59; 95% CI 1.06–2.40; P = 0.02) and oxygenation (odds ratio:1.56; 95% CI 1.04–2.35; P = 0.03) targets. Comparing the substance groups, the use of hypnotics significantly more often enabled the target values for etCO2 to be reached alone (odds ratio:2.79; 95% CI 1.04–7.50; P = 0.04) as well as in combination with a systolic blood pressure ≥ 100 mmHg (odds ratio:4.42; 95% CI 1.03–19.01; P = 0.04).ConclusionsPostcardiac arrest anesthesia in out-of-hospital cardiac arrest is associated with early achievement of respiratory target parameters in prehospital postresuscitation care without evidence of more frequent hemodynamic complications.

Cerclage plus Adjuvant Vaginal Progesterone for Preterm Birth Prevention in Patients with a Short or Dilated Cervix without Prior Preterm Birth.

The primary objective was to determine if vaginal progesterone following cerclage for cervical length <10 mm or cervical dilation in patients without a history of spontaneous preterm birth (sPTB) decreased the risk of preterm birth at <34 weeks' gestation compared with cerclage alone. Secondary objectives were to determine if vaginal progesterone following cerclage (1) decreased the risk of preterm birth at <24, <28, and <37 weeks' gestation and (2) increased the latency period from cerclage placement to delivery compared with treatment with cerclage alone. Multicenter retrospective cohort study from 2015 to 2020 of singleton pregnancies, without prior sPTB, who had cerclage placement <24 weeks' gestation for cervical length <10 mm or cervical dilation. Exposure defined as cerclage plus vaginal progesterone postoperatively (dual therapy) and unexposed as cerclage alone (monotherapy), based on surgeon preference. We included 122 patients, 78 (64%) treated with dual therapy and 44 (36%) treated with monotherapy. In the crude analysis, dual therapy was associated with a lower risk of delivery at <28 weeks' gestation (13%) compared with monotherapy (34%; crude risk ratio: 0.38 [95% confidence interval, CI: 0.19-0.75]). When adjusted for preoperative vaginal progesterone, results were attenuated (adjusted risk ratio: 0.45 [95% CI: 0.20-1.01]). In both the crude and adjusted analyses, the risk of sPTB was not statistically different at <24, <34 or <37 weeks' gestation. Dual therapy was associated with a greater pregnancy latency from cerclage to delivery (16.3 vs. 14.4 weeks; p = 0.04), and greater gestational age at delivery (37.3 vs. 35.8 weeks' gestation; p = 0.02) compared with monotherapy. While not statistically significant, the risk of sPTB was lower at all gestational ages studied in patients treated with dual therapy compared with monotherapy. Dual therapy was associated with longer pregnancy latency and greater gestational age at delivery compared with monotherapy. · Dual therapy did not decrease preterm birth risk compared with monotherapy.. · Dual therapy prolonged pregnancy compared with monotherapy.. · Dual therapy can be considered but further studies are needed..

Comparative Outcomes of Empagliflozin to Dapagliflozin in Patients With Heart Failure

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to have benefits when used in patients with heart failure. The comparative outcomes of SGLT2 inhibitors relative to each other has not been well defined and may impact medication selection. To determine the comparative outcomes of empagliflozin and dapagliflozin on reducing the composite of all-cause mortality and hospitalizations in patients with heart failure. This multicenter retrospective cohort study included patients with heart failure from August 18, 2021, and December 6, 2022, in the TriNetX Research Collaborative, a centralized database of deidentified electronic medical record data from a network of 81 health care organizations. Eligible patients had a diagnosis of heart failure, had never received an SGLT2 inhibitor previously, and were newly started on empagliflozin or dapagliflozin. Patients were followed up for 1 year. Initiation of dapagliflozin or empagliflozin. The primary outcome was the time to the composite of all-cause mortality or hospitalization between study days 1 to 365. Kaplan-Meier analyses, hazard ratios (HRs), and 95% CIs were used to assess the primary outcome. Among 744 914 eligible patients, 28 075 began empagliflozin (15 976 [56.9%]) or dapagliflozin (12 099 [43.1%]). After nearest-neighbor matching for demographics, diagnoses, and medication use, there were 11 077 patients in each group. Of patients who received empagliflozin, 9247 (57.9%) were male, 3130 (19.6%) were Black individuals, and 9576 (59.9%) were White individuals. Similarly, of those who received dapagliflozin, 7439 (61.5%) were male, 2445 (20.2%) were Black individuals, and 7131 (58.9%) were White individuals. Patients receiving empagliflozin were less likely to experience the composite of all-cause mortality or hospitalization compared with those initiated on dapagliflozin (3545 [32.2%] vs 3828 [34.8%] events; HR, 0.90 [95% CI, 0.86-0.94]) in the year following SGLT2 inhibitor initiation and less likely to be hospitalized (HR, 0.90 [95% CI, 0.86-0.94]). All-cause mortality did not differ between exposure groups (HR, 0.91 [95% CI, 0.82-1.00]). There was no difference in mean hemoglobin A1c or adverse events between groups. In this cohort study, patients who initiated empagliflozin were less likely to experience the composite of all-cause mortality or hospitalization compared with patients who started dapagliflozin. Additional studies are needed to confirm these finding.

Abstract PO4-01-09: The Prognostic Impact of Adjuvant Endocrine Therapy by Age for Patients with Small Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer

Abstract Backgrounds: We previously reported an analysis of the impact of adjuvant endocrine therapy (ET) for patients with ER+ and HER2- T1a/bN0M0 breast cancer (BC) at ASCO 2023 (Abstract #538). For the whole cohort, adjuvant ET significantly reduced distant metastases, but the absolute overall survival (OS) difference was small. The presence of medical comorbidities related to treatment toxicity and the estimated life-expectancy differ based on age, affecting the clinical impact of ET. There may be settings where comorbidities result in a sufficiently short, expected OS such that the benefit of ET will not outweigh risk. In multivariate analysis, age (&amp;lt;55 vs &amp;gt;55) was not an independent risk factor for distant metastasis. Here we evaluate the impact of adjuvant ET for ER+/HER2- T1a/bN0M0 breast cancer by age-specific subgroups, focusing on younger (&amp;lt; 40) and older (&amp;gt;65) population. Methods: This is a multicenter retrospective cohort study that evaluated the impact of adjuvant ET for patents with ER+/HER2- T1a/bN0M0 BC who underwent primary breast cancer surgery between 2008 and 2012 in 47 institutes of the Japan Clinical Oncology Group (JCOG). We analyzed distant metastatic-free survival (DMFS) and OS using Kaplan-Meier estimates with log-rank test in patients treated with and without ET in each of three age-specific subgroups (&amp;lt;40, 41-64 and 65&amp;gt; years of age). Results: Median follow-up was 9.2 years; the median age of the entire cohort was 55 years. Of 4756 eligible patients, 417 patients were age 65 (1025 (82%) with ET and 227 (18%) without ET). Of all 3989 (84%) patients with ET (2053 (51%) with Tamoxifen, 2142 (54%) with Aromatase inhibitor, 595 (15%) with LH-RH analog and 76 (2%) with others, includes duplicates). In the &amp;lt; 40 subgroup, 9-year DMFS was 97.2% with ET and 91.0% without ET (p=0.023) and 9-year OS was 97.8% with ET and 97.0% without ET (p=0.954). In the &amp;gt; 65 subgroup), 9-year DMFS was 92.6% with ET and 84.0% without ET (p&amp;lt; 0.01) and 9-year OS was 93.8% with ET and 84.9% without ET (p&amp;lt; 0.01). In those aged 41-64, no significant difference was observed in both 9-year DMFS and OS between patients with and without ET (p=0.328 and p=0.731, respectively) See Table for details. Conclusions: Adjuvant endocrine therapy was associated with improved distant metastatic-free survival in the younger (&amp;lt;40) and older (&amp;gt;65) population in this large Japanese dataset and was associated with improved overall survival in those &amp;gt;65. Our findings suggest clinically relevant benefit from ET in both younger and older unselected patients with very small ER+ BC. The lack of benefit in patients aged 41-64 is likely due to individual tumor and treatment factors, which will be evaluated and described in detail at the meeting. Table. The 9-year DMFS and OS of each age-specific three subgroups. *They are analyzed by using Kaplan-Meier estimates with log-rank test between patients treated with and without ET. Citation Format: Yuko Takahashi, Shinsuke Sasada, Naoto Kondo, Hiroya Hashimoto, Kaori Terata, Kumiko Kida, Yasuaki Sagara, Yoichi Naito, Keisei Anan, Takayuki Ueno, Akihiko Suto, Chizuko Kanbayashi, Mina Takahashi, Rikiya Nakamura, Toshiyuki Ishiba, Michiko Tsuneizumi, Seiichiro Nishimura, Yukinori Ozaki, Akihiko Shimomura, Takehiko Sakai, Tsuguo Iwatani, Hideo Shigematsu, Kenji Tamura, Tomomi Fujisawa, Takashi Hojo, Fumitaka Hara, Tadahiko Shien, Hiroji Iwata. The Prognostic Impact of Adjuvant Endocrine Therapy by Age for Patients with Small Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor 2 Negative (HER2-) 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 PO4-01-09.

Abstract PO3-07-09: B3 breast lesions in Asian Centers: malignant upgrade rates and risk factors

Abstract Background Lesions of uncertain malignant potential in the breast (B3 lesions) are composed of a wide spectrum of pathologies with differing risks of breast cancer. With the widespread implementation of screening programs globally, the incidence of these lesions has increased substantially. Asian women tend to have smaller and denser breasts than Western women, making identifying and treating these lesions more challenging. Previous papers quote an upgrade of B3 lesions to malignancy such as ductal carcinoma in situ (DCIS) or cancer at rates of 9.9% to 35.1%. Malignant upgrade on final histology increases patient anxiety and healthcare costs as a second surgical intervention is often required for pathological clearance or lymph node staging. This study aimed to assess the malignant upgrade rate of B3 lesions in Asian women and to evaluate any key factors that may predict the risk of a malignant upgrade. Materials and Methods A retrospective multicentre international study was done on patients at Seoul National University Hospital (SNUH), South Korea, from April 2021 to 2023, and Tan Tock Seng Hospital (TTSH), Singapore, between March 2006 and 2023. Patients who were diagnosed with a B3 lesion on initial breast core needle biopsy and underwent surgical open excision were included in the study. Results A total of 1049 patients were diagnosed with B3 lesions, with 154 (14.7%) upgrading to malignancy. The most common malignancy was DCIS, 118 (76.6%), followed by invasive ductal carcinoma (IDC), 20 (13.0%) and papillary carcinoma, 4 (2.6%). Within the types of B3 lesions, the malignant upgrade rates were found: atypical ductal hyperplasia (ADH), 88/252 (35%); intraductal papilloma (IDP) with atypia, 16/55 (29%); lobular neoplasia (LN), 9/34 (26%); and radial scar (RS), 5/21 (24%). Most patients had both ultrasound and mammographic evaluation, and all lesions in the study were graded BIRADS 4A and above. Univariate analysis showed that age &amp;gt;50 (OR 2.30 [1.61-3.31], p&amp;lt; 0.001), BMI &amp;gt;23 (OR 2.21 [1.20-4.12], p=0.01), post-menopausal status (OR 2.43 [1.34-4.34], p&amp;lt; 0.001), lesion being identified on mammography (OR 3.00 [2.04-4.51], p&amp;lt; 0.001) and presence of microcalcifications on mammography (OR 0.63 [0.41-0.98], p=0.04) were risk factors for malignant upgrade. Conclusion Based on our analysis of Asian women, post-menopausal patients with microcalcifications on mammography and a B3 biopsy result should be treated with a higher degree of suspicion for underlying malignancy. Surgical excision with adequate margins should be routinely considered for B3 lesions such as ADH, IDP with atypia, LN and RS. Avoidance of surgery or vacuum-assisted removal can be considered for younger patients with only ultrasound findings and diagnosis of FEA and IDP. Table 1. Malignant upgrade after excision Table 2. Clinical characteristics of all patients according to malignant upgrade Table 3. Univariate and multivariate analysis for malignant upgrade Citation Format: Wei Wen Ang, Ji-Jung Jung. B3 breast lesions in Asian Centers: malignant upgrade rates and risk factors [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 PO3-07-09.

Abstract PO2-16-07: Real-world eligibility for adjuvant CDK4/6 inhibitors among patients without genomic risk for chemotherapy: a GBECAM multicenter retrospective study

Abstract Background: Oncotype DX (ODX) is a genomic signature (GS) for the prediction of risk of recurrence and benefit of chemotherapy (CT) in both node negative (N0) and positive (N1), hormone receptor positive (HR+), HER2 negative (HER2-) early breast cancer (eBC). ODX was not an inclusion criterion in the MonarchE but was one in the Natalee study, in which trials most patients received neo-adjuvant chemotherapy. We aim to evaluate the proportion of patients potentially eligible for adjuvant CDK4/6 inhibitors (CDK4/6i) without CT indication by genomic risk using real-world data from a large dataset of patients from various Brazilian institutions. Methods: Clinicopathologic and ODX information were reviewed for patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020. Projections of CT indication by genomic criteria were based on TAILORx and RxPONDER data. Projections of adjuvant CDK4/6i indication were based on the MonarchE and Natalee criteria. Results: Of 636 patients, 27.5%/51.8%/20.8% were T1mic-a-b/T1c/T2-3, respectively. 19.5% were grade 1 (G1), 66.9% G2 tumors and 12.9% G3. 74 (11.6%) were N1. The ODX indicated low (&amp;lt; 11), intermediate (11-25) and high ( &amp;gt;25) risk in 117 (18.4%), 408 (64.1%) and 111 (17.5%) patients, respectively. 408 patients (64.2%) had low clinical risk and 228 patients (35.8%) had high clinical risk disease. In the overall cohort, 439 (69%) did not have genomic indication for CT, 25 (3.9%) and 133 (21%) were eligible for adjuvant abemaciclib and ribociclib, respectively. Among patients eligible for adjuvant CDK4/6i, greater than 50% did not meet genomic criteria for recommendation of CT (Table 1). Conclusions: In times of rapid incorporation of both GES (as valuable treatment de-escalation tools) and adjuvant CDK4/6i, our results suggest that a meaningful proportion of patients could be eligible for adjuvant abemaciclib and/or ribociclib independently of CT indication. However, little is currently known about the role of these agents in patients not treated with chemotherapy because they were largely unrepresented in these studies. Proportion of patients eligible for adjuvant CDK4/6i in the overall and non-CT eligible population. CT: chemotherapy Citation Format: Leandro Oliveira, Thais Megid, Daniela Rosa, Daniele Assad-Suzuki, Daniel Argolo, Solange Sanches, Laura Testa, José Bines, Rafael Kaliks, Débora Gagliato, Romualdo Barroso-Sousa, Tatiana Correa, Andrea Shimada, Daniel Batista, Daniel Musse, Marcelle Cesca, Débora Gaudêncio, Larissa Moura, Julio Araujo, Renata Colombo Bonadio, Artur Katz, Max Mano. Real-world eligibility for adjuvant CDK4/6 inhibitors among patients without genomic risk for chemotherapy: a GBECAM multicenter retrospective 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 PO2-16-07.

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.

Assessing the benefits of repeated esophagogastroduodenoscopy at a specialized center before gastric and esophageal cancer surgery.

The surgical treatment of gastric and esophageal cancer in Denmark is centralized in four specialized esophagogastric cancer (EGC) centers. Patients are referred after an esophagogastroduodenoscopy (EGD) at a secondary healthcare facility. The EGD is repeated at the specialized EGC center before determining a surgical treatment strategy. This multicenter retrospective study aimed to investigate the quality of EGDs performed at a secondary healthcare facility and evaluate the clinical value of repeated EGD at a specialized center when determining the surgical treatment strategy. Patients from three of the four centers, who underwent esophagectomy or gastrectomy with curative intent from 1 June 2016 to 1 May 2021, were included. EGD reports from the referral facilities and EGC centers were compared based on a predefined checklist. Furthermore, endoscopist experience, the time between examinations, and histology were registered. Finally, it was assessed whether the specialized EGD led to any substantial changes in surgical treatment. Baseline characteristics and differences in EGD reports were described and McNemar's chi-square test was performed. A logistic regression analysis was conducted to identify risk factors for a change in surgical strategy. The study included 953 patients who underwent both an initial EGD and EGD at referral to a specialized center. In 644 cases (68%), the information from the initial EGD was considered insufficient concerning preoperative tumor information. In 113 (12%) cases, the findings in the specialized EGD would lead to a significant alteration in the surgical strategy compared with the primary EGD. The findings suggest that repeated EGD at a specialized center is of clinical value and helps ensure proper surgical treatment for patients undergoing curative surgery for gastroesophageal cancer.

Abstract PO4-12-10: Sacituzumab Govitecan Toxicity Outcomes In Arab Patients with Metastatic Breast Cancer

Abstract Background: The Arab population is often underrepresented in clinical trials, which limits our knowledge of drug safety and efficacy in this population due to genetic variability that can affect drug metabolism and adverse events (AEs). Sacituzumab govitecan (SG) is approved for metastatic triple negative breast cancer (mTNBC), and recently hormone receptor positive metastatic breast cancer (HR+ MBC). Here we report toxicity outcomes and RDI in Arab population. Methods: A multi-center retrospective study of patients with mTNBC and HR+ MBC treated with SG from January 2021 until May 2023 was conducted. Demographics and clinical variables including site of metastases, prior lines of therapy, relative dose intensity (RDI), adverse events (AEs) 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. SAS v9.4 was used to perform statistical analysis at a significance level of 0.05. Results: A total of 35 patients was enrolled. The median age at diagnosis of metastatic breast cancer was 39 years interquartile range (IQR) (35, 44). The median age at starting SG was 44.5 years IQR (38,50). The majority of patients (65%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 1, (21%) of the patients had an ECOG PS of 0, and (15%) had an ECOG PS of 2. 48.6% received 3 or more lines of prior therapy in the metastatic setting while 51.4% received less than 3 lines of prior therapy in the metastatic setting. 77.1% of patients had 3 or &amp;gt; organs involved with metastatic disease, while 22.9% of patients had &amp;lt; 3 organ involved. The most common metastatic sites were the lung (54.3%), liver (62.9%), bone (68.6%), and brain (45.7%). The median RDI of SG was 100% for a sample of 34 individuals, with one missing value IQR (94%,100%). The rate of overall AEs was (77.1%), with the most common AEs being; neutropenia (44.4%), diarrhea (37.0%), anemia (22.2%), thrombocytopenia (22.2%), nausea (14.8%), and vomiting (7.4%). Garde 3 AEs rate was 34.3%. The most common grade 3 adverse events were diarrhea (11.4%), fatigue (5.7%), and alopecia (2.9%). The rate of treatment interruption and dose reduction due to AEs was 31.4%. Only one patient (2.9%) had to discontinue SG treatment due to adverse events. Conclusion: The study suggests that SG is safe and well-tolerated in young Arab patient population. The sample consisted of relatively young patients, which may reflect a reluctance to prescribe SG to older Arab patients. Caution should be exercised when generalizing the findings due to limitations of the study. Further studies with larger sample sizes are needed to validate these findings and to explore the efficacy of SG in Arab patients with mTNBC and HR+ MBC. Citation Format: Maymouna Altarturi, Kausar Suleman, Adhar AlSayed, Humaid Al-Shamsi, Aydah Alawadhi, Bassam Basuliamn, Sabah Alaklabi. Sacituzumab Govitecan Toxicity Outcomes In Arab Patients with Metastatic 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 PO4-12-10.

Abstract PO3-08-12: Oncologic Safety and Preventive Impact of Nipple-Sparing Mastectomy in BRCA1/2 Mutation Carriers: A Multicenter Retrospective Study of the Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG)

Abstract Purpose: Nipple-sparing mastectomy (NSM) is known for its excellent cosmetic results and acceptable oncologic safety. However, evidence supporting NSM in breast cancer (BC) patients carrying pathogenic variant (PV) or likely pathogenic variant (LPV) in BRCA1/2 genes is still limited. This study aims to evaluate the oncologic safety of NSM in BC patients and examine its preventive effect in unaffected individuals with BRCA1/2 PV/LPV. Methods: In this multicenter, retrospective study was conducted by the Korea Robot-Endoscopic minimal access Breast Surgery study Group (KoREa-BSG). We evaluated data from women who underwent NSM and BRCA1/2 genetic testing across 19 South Korean institutions. This study included BC patients aged between 20 and 80 years who had NSM and BRCA1/2 genetic testing between January 2008 and December 2018. Patients with distant metastasis at the initial diagnosis were excluded. Results: A total of 786 women, encompassing 906 NSM cases, were included. This population comprised 120 patients who underwent bilateral NSM, 666 with unilateral NSM for unilateral BC. Among them, 214 who received neoadjuvant chemotherapy. The median follow-up period was 62 months, with an age range of 26-74 years (median 44). Sentinel lymph node biopsy was carried out in 74.7% of cases. In the bilateral NSM cohort (n=120), 36 were bilateral BC patients, 41 were unaffected carriers of BRCA1/2 PV/LPV who underwent bilateral risk-reducing NSM (RRNSM), and 33 presented with unilateral BC with BRCA1/2 PV/LPV. In the subset of 33 patients who underwent contralateral RRNSM for unilateral BC, incidental ductal carcinoma in situ (DCIS) was discovered in two cases. In comparing NSM outcomes according to BRCA status, we found no significant difference in local recurrence (LR) between BC patients with BRCA1/2 PV/LPV (n=172) and those without BRCA1/2 PV/LPV (n=592) (LR rates: 11 in BRCA1/2 PV/LPV vs. 45 in non-carriers; p = 0.7965). Of the 172 BRCA1/2 PV/LPV carriers who did not undergo RRNSM, contralateral BC occurred in 11 patients (6.4%), while no recurrence was recorded in the RRNSM group. Conclusions: NSM appears to be a feasible option in BC patients with BRCA1/2 PV/LPV. While the long-term impact of NSM on breast cancer prevention in BRCA1/2 PV/LPV carriers requires further investigation, current evidence suggests that NSM could serve as an effective risk-reducing strategy. Citation Format: Hong-Kyu Kim, Sung Yoon Jang, Soong June Bae, Eun Young Kim, Chihwan Cha, Hyung Seok Park, Jeeyeon Lee, Jun-Hee Lee, Eun-Shin Lee, Jung Eun Choi, Soo Youn Bae, Hee-Chul Shin, Dongwon Kim, Moo Hyun Lee, Yong-Yeup Kim, Sang-Ah Han, Janghee Lee, Youngwoo Chang, Junwon Min, Sanghwa Kim, Hee Jun Choi, Young-Joon Kang, Sae Byul Lee, Jai Min Ryu. Oncologic Safety and Preventive Impact of Nipple-Sparing Mastectomy in BRCA1/2 Mutation Carriers: A Multicenter Retrospective Study of the Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) [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 PO3-08-12.

Abstract PS08-02: Efficacy of Sacituzumab-Govitecan (SG) post Trastuzumab-deruxtecan (T-DXd) and vice versa for HER2low advanced or metastatic breast cancer (MBC): a French multicentre retrospective study

Abstract Background: Based on ASCENT, TROPICS-02 and DESTINY-Breast04 trials, SG and T-DXd recently became approved for HER2low MBC. Since the payloads of both SG and T-DXd belong to the same cytotoxic class (topoisomerase-1 inhibitor), cross-resistance is a potential concern. However, no data is available on the efficacy of one antibody drug conjugate (ADC) after another and the best therapeutic sequence has not been evaluated yet. Methods: We conducted a retrospective study in 19 French comprehensive cancer centres. All patients (pts) with HR+ or HR- and HER2low MBC treated with SG followed, immediately or not, by T-DXd (or vice versa) were included. HR expression was defined on the last available tumor sample. The study primary objective was to report the second ADC (ADC2) progression-free survival (PFS) in the whole population. Secondary objectives included first ADC (ADC1) progression-free interval (PFI) and overall survival (OS) in the whole population and subgroup analyses by HR status. Results: The individual data of 126 eligible women were obtained from 19 participating centres. Median age was 54.5 years (range: 30-80y). N=110 (87.3%) pts had invasive carcinoma of not special type, N=12 (9.5%) invasive lobular carcinoma and 4 (3.2%) other histological subtype. N=87 (69%) and 39 (31%) had HR+/HER2low and HR-/HER2low MBC, respectively. N=16 patients were germline mutation carriers (BRCA1 N=7; BRCA2 N=6; other genes on HBOC panel N=3). ADC1 was given as a median of third (range: 1-10) line of chemotherapy and ADC2 as fifth (range: 2-12) line. A large majority (N=94, 74.6%) of pts received SG as ADC1 (N=82 with HR- and N=12 with HR+ MBC) while N=32 (25.4%) received T-DXd as ADC1 (N=27 with HR+ and n=5 with HR- MBC). 53.2% (N=67) received ADC1 immediately followed by ADC2 while 46.8% (N=59) received ADC2 after 1 (N=40) or 2 (N=12) or ≥ 3 (N=6) other lines of chemotherapy. N=19 (15.07%) and N=26 (20.63%) had a meningeal and/or cerebral metastasis at the time of the initiation of ADC1 and ADC2 respectively. After a median follow-up of 3 months, ADC2 was discontinued in 63 pts of which 51 (82.3%) for progression disease and 4 (6.5%) for toxicity due to T-DXd. Importantly, 50% of pts (N=63) were still under ADC2 at the time of this first analysis. The observed median PFS for ADC2 and median PFI for ADC1 are presented in the Table below: Median OS was not reached independently of the sub-populations of pts. Population and sequential regimen Median (mo) PFI ADC1 Median (mo) PFS ADC2 Whole population (N=126) SG → T-DXd (N=94) T-DXd→SG (N=32) 4.5 (95%CI [3.4-5.1]) 2.7 (95%CI [2.1-3.3] HR-/HER2low (N=82) having received SG as ADC1 then T-DXd as ADC2 4.8 (95%CI [3.8-5.1]) 3.3 (95%CI [2.5-3.7]) HR+/HER2low (n=27) having received T-DXd as ADC1 then SG as ADC2 2.7 (95%CI [2.0-3.2]) 2.0 (95%CI [1.6-NR]) Conclusion: To the best of our knowledge, this is the largest cohort evaluating the efficacy of subsequent ADCs administration in HER2low MBC. In these heavily pre-treated pts, subsequent use of ADCs seem to be associated with shortened PFS in both HR+/HR- subgroups, independently of their administration order. Data will be updated and completed for the meeting. Moreover, the number of eligible pts will be increased. Table 1: median TPP and PFS2 in whole population and HR subgroups Citation Format: François Poumeaud, Mathilde Morisseau, Luc Cabel, Anthony Gonçalves, Charlène Rivier, Olivier Trédan, Elsa Volant, Jean Sebastien FRENEL, Sylvain Ladoire, William Jacot, Mathieu Jamelot, Hervé Fokatichoue, Luis Teixeira, Francois-Clement Bidard, Delphine Loirat, Christelle Levy, Bastien Cabarrou, Antoine Deleuze, Elise Deluche, Thomas Grellety, Frédéric Fiteni, Hervé Bischoff, Roman Vion, Stéphanie Becourt, Thibaut Reverdy, Alexandre de Nonneville, Florence Dalenc. Efficacy of Sacituzumab-Govitecan (SG) post Trastuzumab-deruxtecan (T-DXd) and vice versa for HER2low advanced or metastatic breast cancer (MBC): a French multicentre retrospective 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 PS08-02.

Abstract PO2-01-14: Development of Artificial Intelligence-based Machine Learning Models for Predicting Survival In Hormone-Receptor-Positive/HER2-Negative Early Breast Cancer undergoing Neoadjuvant Chemotherapy

Abstract Background. In hormone-receptor positive (HoR)/HER2 negative early breast cancer (BC) multiple efforts have been made to predict disease recurrence and survival. Machine learning techniques have been used but few studies have looked into their applicability in predicting survival on the basis of clinico-pathological characteristics. The aim of this study was to evaluate a random survival forest model to predict the prognosis of this specific BC subtype. Methods. In this multicenter, retrospective study, patients who fulfilled the following inclusion criteria were included: (1) diagnosis of pathologically confirmed HoR-positive/HER2-negative invasive BC; (2) early or locally advanced, stage I-II-III (3) patients receiving neoadjuvant anthracycline and/or taxane-based chemotherapy, concurrently or sequentially; (4) patients undergoing surgery for primary BC. Survival endpoints were disease-free survival (DFS) and overall survival (OS). A random survival forest algorithm was used to develop the predictive model. Ten-fold cross-validation was performed. The C-index and the continuous rank probability score (CRPS) were used to evaluate the discrimination of the predictive model, and a ROC curve was used to evaluate model precision. A cut point analysis based on maximally selected rank statistics was conducted to evaluate the best cut-off in the out-of-bag (OOB) mortality that could maximize DFS and OS prediction. Variable importance was assessed using Breiman-Cutler permutation importance. Results. Overall, 572 patients with HoR-positive/HER2-negative early BC were included. At univariate analysis age, T stage, N stage, grading, ER, PR and Ki67 were found to be significantly associated with DFS and ER, PgR, HER2, pCR ypT and ypN retained statistical significance at multivariate analysis. ER, pCR, pathological T and N stage were found to be significantly associated with OS at univariate and multivariate analysis. The following variables were included in the final model: menopausal status, age, histology, grade, clinical T/N, ER/PgR, Ki67 and HER2, pathological complete response (pCR), ypT and ypN. For DFS, the cross-validated C-index was 0.68 (95% CI 0.63-0.73) and the OOB CRPS was 0.15, with a OOB performance error of 0.31. The AUC calculated at 60 months was 0.91 (95% CI 0.88-0.94). Out-of bag RSF-based risk scores for individual patients were calculated and an optimal cut-off of 22.58 was identified. The HR between high risk and low risk group was 3.08 (95% CI 2.16-4.39, p&amp;lt; 0.001). For OS, the cross-validated C-index was 0.66 (95% CI 0.60-0.71) and the OOB CRPS was 0.17, with a OOB performance error of 0.35. The AUC calculated at 60 months 0.91 (95% CI 0.88-0.95). An optimal cut-off of 21.54 was identified and the HR between low risk and high risk group was 2.50 (95% CI 1.73-3.61, p&amp;lt; 0.001). For DFS, the most important variables were cN (9.00), ypN (7.35), ER (7.21), ypT (5.38), PgR (4.11), pCR (4.01) and age (2.82) while for OS the most important variables were cN (7.88), ER (5.37), PgR (3.61), age (3.37), pCR (2.80), ypT (2.64) and ypN (2.60). Discussion. We analyzed the performance of RSF in the prediction of DFS and OS based on the contribution of clinico-pathological features commonly available at the baseline of the NCT and post-surgery. By selecting patients with HoR-positive HER2-negative disease, we were able to show which clinico-pathological features within a ML model have greater predictive importance. The model could be integrated with image-based tumor and radiology features to improve its predictive accuracy. This retrospective multicenter study suggests that the combination of easily accessible clinico-pathological features within a ML model may reliably predict DFS and OS in the context of HoR-positive/HER2-negative BCs. Citation Format: Luca Mastrantoni, Giovanna Garufi, Noemi Maliziola, Elena Di Monte, Giorgia Arcuri, Valentina Frescura, Angelachiara Rotondi, Giulia Giordano, Luisa Carbognin, Alessandra Fabi, Ida Paris, Gianluca Franceschini, Armando Orlandi, Antonella Palazzo, Giovanni Scambia, Giampaolo Tortora, Emilio Bria. Development of Artificial Intelligence-based Machine Learning Models for Predicting Survival In Hormone-Receptor-Positive/HER2-Negative Early Breast Cancer undergoing Neoadjuvant Chemotherapy [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 PO2-01-14.

Risk factors for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome: A multicenter retrospective study.

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS-associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013-September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality-related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42-day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42-day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non-antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826-0.884) and 0.778 (95% CI: 0.702-0.854) for SAPA onset and 42-day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14-day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS-endemic areas is crucial, with effective predictive tool.

Diagnostic performance of artificial intelligence in interpreting thyroid nodules on ultrasound images: a multicenter retrospective study.

Thyroid nodules are commonly identified through ultrasound imaging, which plays a crucial role in the early detection of malignancy. The diagnostic accuracy, however, is significantly influenced by the expertise of radiologists, the quality of equipment, and image acquisition techniques. This variability underscores the critical need for computational tools that support diagnosis. This retrospective study evaluates an artificial intelligence (AI)-driven system for thyroid nodule assessment, integrating clinical practices from multiple prominent Thai medical centers. We included patients who underwent thyroid ultrasonography complemented by ultrasound-guided fine needle aspiration (FNA) between January 2015 and March 2021. Participants formed a consecutive series, enhancing the study's validity. A comparative analysis was conducted between the AI model's diagnostic performance and that of both an experienced radiologist and a third-year radiology resident, using a dataset of 600 ultrasound images from three distinguished Thai medical institutions, each verified with cytological findings. The AI system demonstrated superior diagnostic performance, with an overall sensitivity of 80% [95% confidence interval (CI): 59.3-93.2%] and specificity of 71.4% (95% CI: 53.7-85.4%). At Siriraj Hospital, the AI achieved a sensitivity of 90.0% (95% CI: 55.5-99.8%), specificity of 100.0% (95% CI: 69.2-100%), positive prediction value (PPV) of 100.0%, negative prediction value (NPV) of 90.9%, and an overall accuracy of 95.0%, indicating the benefits of AI's extensive training across diverse datasets. The experienced radiologist's sensitivity was 40.0% (95% CI: 21.1-61.3%), while the specificity was 80.0% (95% CIs: 63.6-91.6%), respectively, showing that the AI significantly outperformed the radiologist in terms of sensitivity (P=0.043) while maintaining comparable specificity. The inter-observer variability analysis indicated a moderate agreement (K=0.53) between the radiologist and the resident, contrasting with fair agreement (K=0.37/0.33) when each was compared with the AI system. Notably, 95% CIs for these diagnostic indexes highlight the AI system's consistent performance across different settings. The findings advocate for the integration of AI into clinical settings to enhance the diagnostic accuracy of radiologists in assessing thyroid nodules. The AI system, designed as a supportive tool rather than a replacement, promises to revolutionize thyroid nodule diagnosis and management by providing a high level of diagnostic precision.

Risk factors of periprosthetic joint infection after hemiarthroplasty for displaced femoral neck fracture in the elderly: Analysis of 1619 cases in the multicenter database

PurposeThis multicenter retrospective study focuses on understanding the incidence, causative bacteria, and risk factors for Periprosthetic Joint Infection (PJI) following hemiarthroplasty in elderly patients with displaced femoral neck fractures (FNF). MethodsFrom 2016 to 2020, 1,619 patients were diagnosed with displaced FNFs and treated surgically across 11 centers. After exclusions, 1,438 patients (399 men and 1,039 women) were included in the study, averaging 82.1 years in age and 20.2 kg/m² in BMI, observed over 25.7 months on average. Data on demographics, medical history, surgical details, and complications were described. ResultsPJI occurred in 20 of the 1438 patients (1.4%). The causative organism was methicillin-susceptible Staphylococcus aureus in 6 patients and methicillin-resistant S. aureus in 6 patients. In patients' backgrounds, the average age was slightly higher in the non-PJI group (82.1 years) compared to the PJI group (80.4 years). There was a higher percentage of males in the PJI group (45%) than in the non-PJI group (27.5%). Drug history showed that the prevalence of anticoagulant use in the PJI group was 25%. Peripheral vascular disease and diabetes mellitus were more prevalent in the PJI group. Most patients in both groups were independent in daily activities. The blood transfusion rate was significantly higher in the PJI group (50%) than in the non-PJI group (23.8%). Notably, the incidence of hematoma was higher in the PJI group (40%). ConclusionThis multicenter retrospective study demonstrates a low incidence (1.4%) of PJI in elderly patients undergoing hemiarthroplasty for FNF, primarily due to Staphylococcus aureus. Increased usage of antiplatelets and anticoagulants, as well as comorbidities related to atherosclerosis, like peripheral vascular disease and diabetes mellitus, were observed in patients with PJI. Additionally, these patients experienced higher rates of blood transfusion and postoperative hematomas, highlighting the need for careful management. It should be noted, however, that this finding is a conclusion limited by study design issues, including the retrospective design, small PJI sample size, and variability in treatment approaches.

Survival Analysis up to 8 Years of 304 Anatomic-Contour Implant Zirconia Crowns Fabricated with a Fully Digital Cast-Free Workflow and Directly Screwed on External Hexagonal Implant Connections without the Interposition of a Ti-Base: A Multicentric Retrospective Study.

Data on the clinical performance of monolithic Zirconia screw-retained crowns on external hexagon implants fabricated from digital scans through a cast-free, fully digital workflow is lacking and needs to be included. This retrospective multicentric study aimed to evaluate the real-life clinical results of monolithic Zirconia screw-retained crowns without the interposition of a Ti-base on external hexagon implants fabricated from intraoral scans and a cast-free approach in private practices. Single external hex implant fixtures were restored with monolithic zirconia crowns without the interposition of a Tibase. The crowns were directly screwed on external hexagonal implant connections with a castfree, fully digital workflow. Data were analyzed using descriptive statistics and the Kaplan- Meier test. Between September 2022 and March 2023, the California Dental Association modified criteria were adopted for clinical evaluation after recalling all patients. A total of 304 single tooth restorations in the maxillary and mandibular posterior regions fabricated between July 2014 and July 2022 in 252 patients (120 males and 132 females, mean age 53.6 years, SD 23.3). Seven crowns were excluded because of patient dropout. The most common minor technical complications were screw loosening (3 crowns) and loss of the screw-access hole filling (3 crowns). Four failures included two implant failures with mobility and two fractured crowns. No screw or implant fractures were recorded. The overall cumulative survival rate was 98.6% and the average success rate (crowns experiencing no failures or complications) was 96.0%. The mean overall survival time was 101.3 months (standard error, 0.847; 95% confidence interval for the mean, 99.67-102.99). The overall survival probability was 87.9% up to 97 months. With careful case selection and comprehensive periodontal maintenance program, single crowns directly screwed onto an external hexagon platform have shown to have excellent survival and success (complication-free) rates, comparable to available data regarding single crowns with a metal implant- prosthetic interface.