Risk Of Recurrence In Patients Research Articles

Abstract PS01-07: Impact of Race and Ethnicity on Recurrence Risk in Patients with Ductal Carcinoma in Situ Treated with Breast-Conserving Surgery

Abstract Background: Among women with invasive breast cancer, clinical presentation, tumor biology and survival vary by race and ethnicity. However, the impact of race and ethnicity on clinical presentation and recurrence risk in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) has not been well studied. We sought to compare rates of recurrence in women with DCIS across racial and ethnic groups and identify factors associated with recurrence. Methods: Patients with DCIS treated with BCS from 1978 to 2016 at a single institution were identified. Patients were grouped and analyzed based on self-reported race and ethnicity as: Asian, Hispanic, non-Hispanic Black (Black), non-Hispanic White (White). Individuals with undefined ethnicity were classified by race, while those lacking both race and ethnicity data were excluded. Clinicopathologic characteristics were compared across racial and ethnic groups. The association of race and ethnicity on recurrence risk was analyzed using Kaplan–Meier methods, competing risk analysis and multivariable analysis. Results: Overall, 4207 cases were included, of which 6% (n= 261) were Asian, 9% (n = 358) Black, 5% (n = 226) Hispanic and 80% (n = 3362) White. Median age was 57 years (IQR 49, 67), 56% received radiotherapy (RT) and 26% received endocrine therapy. Black women with DCIS were older; Asian women were younger (median age: 60 vs 53 respectively, p < 0.001). Black women were more likely to have a clinical presentation (p = 0.006), and Black and Hispanic women were more likely to require ≥3 excisions (p = 0.006). The use of RT was most common among Hispanic women (p = 0.02). At a median follow-up of 8.8 years, 602 (14%) had local recurrence (LR) (315 [52%] DCIS; 284 [47%] invasive and 3 [ < 1%] unknown). The 10-year rate of LR was 15% and was lower in those treated with RT than without (11% vs 20%, respectively; p< 0.0001), despite those receiving RT having more high-risk characteristics. Rates of LR varied significantly by race and ethnicity, with the highest 10-year rate in Black women (25%) compared with Asian (11%), Hispanic (15%) and White (14%) women (p = 0.03). This statistically significant difference persisted among the no RT cohort (10-year rate: 31% [Black], 13% [Asian], 25% [Hispanic], 19% [White], p = 0.043), but did not reach significance in the RT cohort (21% [Black], 9% [Asian], 9% [Hispanic] and 11% [White], p = 0.3). Using competing risk analysis, the risk of invasive recurrence was similar or lower than DCIS recurrence in each racial group with or without RT. After adjusting for other factors on multivariable analysis, there remained a higher risk of LR among Black women (hazard ratio [HR] 1.48, 95% CI 1.12-1.95, p = 0.01). Older age (p < 0.001), radiologic presentation (p = 0.02), margins ≥ 2 mm (p < 0.001), the use of endocrine therapy (p < 0.001) and the use of RT (p < 0.001) were associated with lower rates of LR (Table). Sixteen women (0.4%) developed distant disease, with similar rates among Asian (0%), Black (0.8%), Hispanic (0.9%) and White (0.3%) women (p = 0.2). Conclusion: Compared with Asian, Hispanic and White women, Black women with DCIS had a significantly higher rate of LR after BCS, even after adjusting for known clinicopathologic risk factors. Rates of distant recurrence were low, and similar across racial groups. These higher rates of LR should be considered when making decisions about adjuvant therapy. Table. Factors associated with local recurrence in women with ductal carcinoma in situ treated with breast-conserving surgery. HR, hazard ratio; CI confidence interval; Ref, referent. Citation Format: Natália Polidorio, V. Morgan Jones, Varadan Sevilimedu, Monica Morrow, Kimberly Van Zee, Andrea Barrio. Impact of Race and Ethnicity on Recurrence Risk in Patients with Ductal Carcinoma in Situ Treated with Breast-Conserving Surgery [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 PS01-07.

Abstract PO4-20-03: HIPEx: Adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative early breast cancer with high recurrence score according to GenesWellTM BCT; a multi-center single arm phase II clinical trial (KCSG BR 19-13)

Abstract Background: In estrogen receptor (ER)-positive human epidermal growth factor receptor2 (HER2)-negative early breast cancer (EBC) patients, NCCN treatment guideline recommend 21-gene tests for decision of adjuvant chemotherapy if tumor size is over 0.5cm or node positive disease. In addition, GenesWellTM BCT is a prognostic assay that predict the risk of recurrence in patients with ER-positive HER2-negative and nodal stage 0-1 EBC. According to gene tests, EBC patients with high recurrence risk would have help from adjuvant chemotherapy to increase the rate of disease free survival but toxicities of chemotherapy are not negligible. Therefore, the effort for escaping adjuvant chemotherapy has been performed and currently CDK4/6 inhibitor would be considered as the substitute for cytotoxic chemotherapy in ER-positive HER2-negative EBC patients. Methods: HIPEx trial is a multi-center, phase II clinical trial to determine the efficacy of adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative EBC with high recurrence score according to GenesWellTM BCT (NCT04247633). Eligible patients are women who received curative surgery and diagnosed as ER-positive, HER2-negative and pathologic stage T1b-T2 and/or N0-1. Clinical recurrence risk is high according to the modified Adjuvant! Online guideline and GenesWellTM BCT score is 4 or more which being genomic high risk. Other criteria include ECOG performance status ≤1, adequate organ functions and availability of an archival surgical specimens. Patients receive palbociclib 125mg once daily for 21 days of 28-day cycle plus tamoxifen or aromatase inhibitor (anastrozole, letrozole or exemestane) once daily for every day. Palbociclib would be taken for two years and endocrine therapy for five years or more. If adjuvant radiotherapy is required, palbociclib should be taken two weeks after the end date of radiotherapy. If patients are premenopausal status, GnRH agonist is allowed. Primary endpoint is 3-year event free survival (EFS) rate of high clinical and genetic risk ER-positive EBC. Secondary endpoints include 3-year overall survival, quality of life, safety and tolerability of palbociclib with endocrine therapy as an adjuvant setting, exploratory analysis of predictive and prognostic biomarkers and the performance of GenesWellTM BCT for 3-year EFS rate. In total, 578 patients would be enrolled in this trial. Based on the previous results of GenesWell™ BCT in Korea, the 3-year EFS rate for the past control group (chemotherapy followed by endocrine therapy) is 87.0% and the treatment group in this clinical trial is assumed to be 90.5%.(hazard ratio for EFS = 0.717). Null hypothesis is the 3year-EFS rate in patients received adjuvant palbociclib and endocrine therapy is not less than that of the past control group. Alternative hypothesis is the 3year-EFS rate of this trial is less than that of the past control group (one-sided). Significance level is 0.025, power is 0.80. Considering 10% drop out rate, 4-years of accrual patient enrollment and 3-years of follow up period, 578 patients were required in this clinical trial. Citation Format: Ji-Yeon Kim, Sung Hoon Sim, Jieun Lee, In Hae Park, Kyong Hwa Park, Seock-Ah Im, Jee Hung Kim, Kyoung Eun Lee, Jeong Eon Lee, Jai Min Ryu, Young Kee Shin, Yeon Hee Park. HIPEx: Adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative early breast cancer with high recurrence score according to GenesWellTM BCT; a multi-center single arm phase II clinical trial (KCSG BR 19-13) [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 PO4-20-03.

Abstract PO5-15-10: Plasticity marker FOXC1 expression accurately predicts efficacy of Adjuvant Tamoxifen + Chemotherapy in reducing all-cause mortality in ER+LN- Breast Cancer: Validation in the SCAN-B Prospective Study (NCT02306096)

Abstract INTRODUCTION: Despite the development and validation of multimarker gene panels like OncotypeDx®, Mammaprint® and EndoPredict®, an affordable and globally accessible biomarker approach that can predict increased risk of all-cause mortality in patients diagnosed with ER+LN- breast cancer, as well as the efficacy of adjuvant endocrine + chemotherapy in mitigating such elevated risk, continues to be an unmet medical need. Lack of such a pragmatic solution continues to be the cause of preventable recurrent/metastatic disease in patients diagnosed with ER+LN- breast cancer in resource-challenged settings around the world. We hypothesized that a predictive biomarker strategy that measures expression of the plasticity marker FOXC1, in combination with clinical parameters like tumor size (TS) and tumor grade (TG), may offer equivalent results to that of the above multimarker gene panels at a significantly lower economic cost without compromising accuracy of prediction results. METHODS: Pre-treatment tumor RNA data obtained from a training cohort (compendium of gene expression microarray datasets, n=2857) and a single large validation cohort (SCAN-B Prospective Multicenter Observational Study, n=3520) for patients diagnosed with ER+LN- breast cancer were analyzed for FOXC1 expression, tumor size (TS) and tumor grade (TG) and correlated with Recurrence-Free Survival (RFS) and Overall Survival (OS). Optimized biomarker cutoff values based on model area-under-curve were leave-one-out cross validated and Risk-of-Recurrence (ROR) prediction algorithm derived utilizing the (compendium) training dataset. The unmodified strategy was then validated in the independent (SCAN-B) validation dataset. RESULTS: A predetermined High ROR score calculated using FOXC1 expression, TS and TG (trained using the compendium dataset) predicted efficacy of adjuvant endocrine + chemotherapy over that of adjuvant endocrine therapy alone in ER+LN- patients in terms of statistically significant reduction in all-cause mortality at 8-years post-diagnosis in the SCAN-B validation dataset (4.66% vs 24.06%, n=326, OR=6.48, 95%CI [2.97-14.11], p< 0.0001). OncotypeDx® (5.7% vs 14.4%, n=762, OR=2.79, 95%CI [1.37-5.67], p=0.002), Mammaprint® (5.1% vs 18.4%, n=665, OR= 95%CI [2.04-8.43], p< 0.0001) and Endopredict® (4.8% vs 15.2%, n=923, OR=3.58 95%CI [1.78-7.21], p=0.0002) were also statistically significant predictors of the same. CONCLUSION: Pre-treatment tumor FOXC1 mRNA or protein expression (assessed using qRT-PCR or routine immunohistochemistry (IHC), respectively, when combined with TS and TG presents a unique and economical alternative solution to multimarker gene panel tests like OncotypeDx®, Mammaprint® or Endopredict®, for guiding therapy of patients diagnosed with ER+LN- breast cancer in resource challenged settings. Such an approach to identify elevated risk of recurrence in patients diagnosed with ER+LN- breast cancer and prevent the same by guiding adjuvant endocrine + chemotherapy decisions, could help to extend recurrence-free and overall survival. Such an approach merits testing in real world ER+LN- patient cohorts in resource-challenged settings to help support implementation of this FOXC1-driven predictive biomarker strategy in the clinic. Citation Format: Partha Ray, Tania Ray, Clive Taylor, Robert Hussa. Plasticity marker FOXC1 expression accurately predicts efficacy of Adjuvant Tamoxifen + Chemotherapy in reducing all-cause mortality in ER+LN- Breast Cancer: Validation in the SCAN-B Prospective Study (NCT02306096) [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 PO5-15-10.

Abstract PS06-08: Longitudinal Neoadjuvant and Post-operative Evaluation of Circulating Tumor DNA in Early Breast Cancer using a Tumor-Informed Assay: Updated Analysis of the TRACER Cohort

Abstract Background: ctDNA is detectable in early breast cancer (EBC) using sensitive assays and treatment-related changes in ctDNA are associated with clinical response. RaDaR® (NeoGenomics), a tumor-informed assay, has been shown to detect circulating tumor DNA (ctDNA) prior to clinical recurrence. We retrospectively quantified ctDNA using RaDaR in serial samples from a large cohort of patients with EBC receiving standard neoadjuvant therapy (NAT). Methods: Unselected patients with EBC were enrolled prior to NAT in the TRACER cohort from 2015 onwards. Plasma samples were collected at baseline, during treatment, perioperatively, and in follow-up. For patients with available tissue for assay generation, RaDaR was performed on all available plasma timepoints. Clinical and pathologic characteristics (assessed on core biopsy), treatment, and outcomes were recorded. Results: Of 128 patients evaluated, 9 (7.0%) were excluded from this analysis due to panel quality control metrics, leaving 119 patients (41 ER+, 32 TNBC, 46 HER2+) with 681 individual timepoints (median=6, range: 1-12). 103/119 patients (86%) received neoadjuvant anthracycline- and taxane-based chemotherapy. Median followup from diagnosis was 3.8 years (range: 0.6-6.3 years) and 16 recurrences have occurred (9 ER+, 6 TN, 1 HER2+). 114 patients had a baseline plasma sample collected prior to NAT, in which the detection rate was 77% (70% ER+, 90% TNBC, 76% HER2+), with a median estimated variant allele frequency (eVAF) of 0.0823% (range: 2.90E-5 - 7.5%). All patients with clinical recurrence had ctDNA detected at baseline. Baseline detection was associated with tumor grade (p=0.050) but not size (p=0.65) or clinical nodal status (p=0.36). There were non-significant associations between eVAF and grade (p=0.097) and eVAF and tumor size (p=0.086). Persistent ctDNA detection midway through neoadjuvant therapy (pre-cycle 5) was associated with an increased risk of recurrence in patients with ER+ (HR: 10.27, 95%CI: 1.61-65.4; p=0.014) and TNBC (HR: 20.17, 95%CI: 1.97-206.4; p=0.011). Residual cancer burden (RCB) status further stratified the risk of recurrence; those with RCB-2/3 disease and ctDNA detected pre-cycle 5 were at the highest risk. Few patients had detectable ctDNA in pre- or initial post-operative specimens, all of which had residual disease (non-pCR). 9/16 patients with clinical recurrence had evaluable post-operative and follow-up samples for lead time calculation; ctDNA was detected prior to recurrence in 7/9 (78 %), with a median lead time of 152 days (range: 13-699 days). Of the 2 patients without a positive test, one had an ipsilateral local recurrence (grade 2, 1.8 mm), the other had a negative, but borderline, test 72 days prior to recurrence (solitary 8 mm lung nodule on PET). Follow up is ongoing for two patients with ctDNA detected but no recurrence at data cutoff (time since last positive test: 0.60 and 1.78 years). Any ctDNA detection postoperatively or in follow-up was strongly associated with disease recurrence (HR: 37.35, 95%CI: 2.7-520.7; p< 0.0001). Conclusion: RaDaR detects ctDNA in most patients prior to the initiation of NAT for EBC. Changes in ctDNA levels during treatment and its presence are associated with clinical outcomes. Prospective evaluation and integration of RaDaR testing into clinical trials are warranted. Further analysis of ctDNA detection, clinical outcomes, and genomic data will be presented at the meeting. Citation Format: Mitchell Elliott, Jesus Fuentes Antras, Philippe Echelard, Aaron Dou, Zachary Veitch, Philippe Bedard, Eitan Amir, Michelle Nadler, Nicholas Meti, Nancy Gregorio, Elizabeth Shah, Celeste Yu, Nathan Campbell, Christodoulos Pipinikas, Karen Howarth, Lillian Siu, Hal Berman, David Cescon. Longitudinal Neoadjuvant and Post-operative Evaluation of Circulating Tumor DNA in Early Breast Cancer using a Tumor-Informed Assay: Updated Analysis of the TRACER 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 PS06-08.

Abstract PO4-01-13: Effect of interruption or discontinuation of endocrine therapy on the prognosis of breast cancer patients: a cohort study using the real-world database

Abstract Background:Adjuvant endocrine therapy is the most important treatment modality as long as one, which can reduce the mortality risk and the recurrence risk for patients with hormone receptor-positive breast cancer. Currently, few studies has reported the association in poor adherence with overall survival(OS) or disease-free-survival(DFS). However, the use of prescription coverage in previous studies to describe patient adherence to endocrine therapy may not be representative of the patient's actual medication. Additionally, previous studies did not distinguish between interruption and discontinuation of endocrine therapy, which is different to clinician. This research used rigorous follow-up data and aims on the effects of discontinuation and interruption on patients with early-stage hormone receptor-positive breast cancer. Methods: Based on the Breast Cancer Information Management System (BCIMS), we identified patients diagnosed with stage I-III breast cancer with hormone receptor-positive and received endocrine therapy during January 1, 1990 to January 1, 2018 in West China Hospital (WCH), Sichuan University, China. Briefly, all patients diagnosed with breast cancer were included and prospectively followed from the diagnosis at WCH or the first visit to WCH for breast cancer. Information, including demographic characteristics, medical history, laboratory results, pathological information, treatments and clinical outcomes, were obtained from clinical records and interviews. Kaplan-Meier analysis, Time-Dependent Cox Regression Model, and subgroup analysis were performed to evaluate the effectiveness of interruption or discontinuation of endocrine therapy. And “X-tile” software is used to select cutoff values in survivorship data. Results:A total of 3,418 eligible patients were included with 8.13(±1.96) years median follow-up. Of these patients, 19.5% did not adhere to standard endocrine regimens, with 6.9% discontinuing and 12.7% discontinuing. The multivariate cox analysis indicates that discontinuation group (DFS:HR=9.71, [95%CI]5.21-18.34,P <0.001; OS:HR=10.41, [95%CI]5.63-19.24,P <0.001) increased the risk of death and breast cancer events compared to the adherence group, but not shown statistical significance difference in the interruption (DFS:HR=1.03,[95%CI]0.23-4.66, P =0.975; OS:HR=1.17, [95%CI]0.26-5.28,P =0.840). We further analyzed the interruption and discontinuation group respectively. In the interruption group, we found cutoff value with 30 months in survival risks but didn't find statistical significance difference in DFS and OS compared to the adherence groups. For the discontinuation group, we divided the patients into low-risk and high-risk groups according to cutoff value (23 months), the final results showed that the high-risk group who took the endocrine therapy less than 23 months had increased the rate of OS(HR=23.98,[95%CI]11.71-49.14, P< 0.001) and DFS(HR=24.03,[95%CI]11.51-50.18, P< 0.001). Conclusion:This study found that interruption of endocrine therapy may not affect prognosis of HR+ breast cancer patients, but prolonged discontinuation increases the risk of relapse and death. Therefore, clinicians should educate patients taking endocrine therapy and encourage those who discontinue the drug to take the drug again as soon as possible. A.Kaplan-Meier Curve for OS B.A.Kaplan-Meier Curve for DFS Kaplan-Meier Curve for OS and DFS in the Interruption Group according to the events location Kaplan-Meier Curve for OS and DFS in the Discontinuation Group according to the total duration of medication Citation Format: Ya Huang, Jie Chen, Yunhao Wu. Effect of interruption or discontinuation of endocrine therapy on the prognosis of breast cancer patients: a cohort study using the real-world database [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 PO4-01-13.

Sex-based differences and risk of recurrence in patients with atrial fibrillation undergoing pulmonary vein isolation

IntroductionStudies suggest increased likelihood of atrial fibrillation (AF) recurrence after catheter ablation (CA) in women than in men, indicating that sex may be an independent risk factor for recurrence. Nevertheless, the influence of sex on AF recurrence and underlying mechanisms remains unclear. MethodsRetrospective, single-centre study including patients undergoing AF CA between 2017 and 2021. Late recurrence (LR) was defined as AF recurrence ≥90 days after ablation, whereas early recurrence (ER) occurred within 90 days. Results656 patients (32% women) were included, with a median follow-up period of 26 months. Compared to men, women undergoing CA were older, had higher body mass indexes, and had higher rates of hypertension, thyroid dysfunction, and valvular disease. Women also had increased LR risk after CA (HR 1.76, 95% CI [1.19, 2.59]). A time-split multivariable analysis at one year of follow-up showed no difference in LR risk during the first 12 months after CA (HR 1.19, 95% CI [0.73, 1.94]); however, LR risk increased in women (HR 2.90, 95% CI [1.68, 5.01]) after 12 months. In a sex-stratified analysis, coronary calcium score (CCS) >100 was associated with increased LR risk in men (HR 1.81, 95% CI [1.06, 3.08]), but not in women. Cardiac adipose tissue volume (CATV) was not associated with increased LR risk. ConclusionsFewer women underwent CA than men and LR was more frequent in women, particularly one year after the procedure. CCS was associated with increased LR risk in men.

Secondary prophylaxis for Clostridioides difficile infection for patients on non- Clostridioides difficile antibiotics: A retrospective cohort study

ObjectivesRecurrent Clostridioides difficile infection (CDI) poses healthcare challenges and morbidity. Preventing recurrence with prophylactic oral CDI antibiotics lack consensus. MethodsWe used data from the largest healthcare provider in Israel to identify all adults aged 18 years or older diagnosed with a first episode of CDI (Index CDI) between February 2018 and December 2022 and subsequently received a non-CDI antibiotic within 2-8 weeks. Patients who received a concurrent prophylactic CDI antibiotic constituted the CDI prophylaxis group. Multivariable Cox proportional hazard regression models were used to examine the association of secondary CDI prophylaxis with CDI recurrence according to the severity of the index CDI (primary objective) and with 4- and 8-week all-cause mortality (secondary objective). ResultsA total of 434 eligible patients were included. Among them, 327 did not receive CDI antibiotic prophylaxis, while 107 did. CDI antibiotic prophylaxis was associated with a significant risk reduction of CDI recurrence with an adjusted HR of 0.51 (95% CI, 0.27-0.97). The magnitude of the association was modified by the severity of the index CDI episode (P for interaction 0.0182). Specifically, the HR for recurrence was 0.163 (95% CI 0.045-0.593) for non-severe CDI, and 1.242 (95% CI 0.524-2.946) for severe CDI. No significant association was found between CDI antibiotic prophylaxis and 4- 8 weeks mortality. ConclusionSecondary prophylaxis with CDI antibiotics appears to be associated with a reduced risk of recurrence in patients with previous non-severe CDI episode. Further studies are needed to confirm this finding.

The added value of ultrasound imaging biomarkers to clinicopathological factors for the prediction of high-risk Oncotype DX recurrence scores in patients with breast cancer.

The Oncotype DX (ODX) recurrence score (RS), a 21-gene assay, has been proven to recognize patients at high risk of recurrence (RS ≥26) who would benefit from chemotherapy. However, it has limited availability and high costs. Our study thus aimed to identify ultrasound (US) imaging biomarkers and develop a prediction model for identifying patients with a high ODX RS. In this retrospective study, consecutive patients with T1-3N0-1M0 breast cancer who were hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative who had an available ODX RS were reviewed. Patients treated from May 2012 and December 2015 were placed into a training cohort, and those treated from January 2016 to January 2017 were placed in a validation cohort. Clinicopathologic data were collected, and preoperative US scans were analyzed. Univariable and multivariable regression analyses were performed to evaluate the independent predictors for a high-risk of breast cancer in the training cohort, and a nomogram was developed and evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). A total of 363 patients were in the training cohort and 160 in the validation cohort, with the proportion with a high RS (RS 26-100) being 14% and 13.1%, respectively. Echogenic halo, enhanced posterior echo, low level of progesterone receptor (PR), and high Ki-67 index were identified as independent risk factors for high RS (all P values <0.05). The nomogram was constructed based on the combined model, which showed a better discrimination ability than did the clinicopathological model [combined model: AUC =0.95, 95% confidence interval (CI): 0.93-0.97; clinicopathological model: AUC =0.89, 95% CI: 0.86-0.92; P=0.001] and greater clinical benefit according to DCA. Furthermore, the nomogram was found to be effective in the validation cohort (AUC =0.90, 95% CI: 0.84-0.94), especially in patients with stage T1N0M0 disease (AUC =0.91, 95% CI: 0.84-0.95). US features may serve as valuable imaging biomarkers for the prediction of high recurrence risk in patients with T1-3N0-1M0 breast cancer and hormone receptor (HR)-positive and HER2-negative status. A nomogram incorporating PR status, Ki-67 index, and US imaging biomarkers showed a good discrimination ability in the early selection of patients at high risk of recurrence, especially in those with stage T1N0M0 disease.

Safety and oncological outcome of early intraoperative intravesicle mitomycin C vs. deferred instillation in patients receiving robot-assisted radical nephroureterectomy.

Radical nephroureterectomy with concurrent bladder cuff excision (RNUBCE) is the gold standard surgical approach for high-risk primary upper tract urothelial carcinoma (UTUC). Given the notably high incidence of bladder tumor recurrence following this procedure, this study aimed to evaluate the effect and safety of intraoperative mitomycin-C (MMC) instillation vs. deferred instillation on overall oncological outcomes following robot-assisted RNUBCE. This is a retrospective chart review study. Patients with non-invasive (N0, not T3/T4) UTUC who underwent robotic RNUBCE combined an intraoperative MMC instillation or a deferred MMC instillation after surgery at a medical center in Taiwan between November 2013 and June 2020 were eligible for inclusion. Patients with prior bladder UC, carcinomas of other origins, received neoadjuvant chemotherapy, and had undergone kidney transplantation were excluded. All surgeries were executed by a single surgical team under the guidance of the same surgeon. The primary outcomes was the risk of bladder tumor recurrence between patients received intraoperative (IO) vs. deferred MMC instillation postoperatively (PO) during one-year follow-up. The secondary outcome was postoperative adverse events assessed by the Clavien-Dindo classification. Univariate and multivariable Cox regression analyses were performed to determine the associations between study variables and the outcomes. A total of 54 patients were included in the analysis. 12 (22.2%) patients experienced a bladder tumor recurrence during follow-up (IO: 7.7%, PO: 35.7%, p < 0.021). After adjustment in the multivariable, intraoperative MMC instillation was significantly associated with lower risk of bladder recurrence [adjusted hazard ratio (aHR) = 0.15, 95% CI: 0.03-0.81, p = 0.028]. No MMC-related Clavien-Dindo Grade III-IV adverse events were found in either group. IIntraoperative MMC instillation is safe and associated with a lower bladder tumor recurrence risk in patients undergoing robotic RNUBCE for UTUC than deferred instillation. Future large, prospective studies are still warranted to confirm the findings.

Novel molecular typing reveals the risk of recurrence in patients with early-stage papillary thyroid cancer

BackgroundPapillary thyroid cancer (PTC) is an indolent disease with a favorable prognosis but characterized by a high recurrence rate. We aimed to improve precise stratification of recurrence risk in PTC patients with early stage using multi-gene signatures.Patients and methodsThe present study was performed using data from The Cancer Genome Atlas (TCGA) and multi-center datasets. Unsupervised consensus clustering was used to obtain the optimal molecular subtypes and least absolute shrinkage and selection operator (LASSO) analysis was performed to identify potential genes for the construction of recurrence signature. Kaplan-Meier survival analysis and the log-rank test was used to detect survival differences. Harrells concordance index (C-index) was used to assess the performance of the DNA damage repair (DDR) recurrence signature.ResultsThrough screening 8 candidate gene sets, the entire cohort was successfully stratified into two recurrence-related molecular subtypes based on DDR genes: DDR-high subtype and DDR-low subtype. The recurrence rate of DDR-high subtype was significantly lower than DDR-low subtype [HR = 0.288 (95%CI, 0.084–0.986), P = 0.047]. Further, a two-gene DDR recurrence signature was constructed, including PER1 and EME2. The high-risk group showed a significantly worse recurrence-free survival (RFS) than the low-risk group [HR = 10.647 (95%CI, 1.363–83.197), P = 0.024]. The multi-center data demonstrated that proportion of patients with low expression of PER1 and EME2 was higher in the recurrence group than those in the non-recurrence group.ConclusionsThese findings could help accurately and reliably identify PTC patients with high risk of recurrence so that they could receive more radical and aggressive treatment strategies and more rigorous surveillance practices.

Impact of aripiprazole discontinuation in remitted major depressive disorder: a randomized placebo-controlled trial.

The efficacy and safety of antidepressant augmentation therapy with aripiprazole (AATA) has been established; however, the ongoing effects of continuing aripiprazole after remission remain unclear because no studies have examined this issue. We aimed to explore the effect of AATA discontinuation on the major depressive disorder (MDD) recurrence risk in patients with remitted MDD after AATA. This 24-week, multicenter, placebo-controlled, double-blind, randomized trial evaluated recurrence risk in patients with MDD who achieved remission with AATA. Differences in MDD recurrence, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, between the two groups were compared using survival analysis. The differences in depressive symptom severity and social functioning between the two groups were compared using a mixed model with repeated measures. Extrapyramidal symptoms and akathisia were also assessed. Twenty-three participants were randomized and treated. Two patients in each group experienced recurrence during the study. Kaplan-Meier analysis with Log-rank comparison showed no difference in recurrence between groups (p = 0.642). No significant difference in interactions between group and period was observed in the 17-item Hamilton depression rating scale (p = 0.492) or the Social and Occupational Functioning Assessment Scale (p = 0.638). No patients developed extrapyramidal symptoms or akathisia. Definitive conclusions could not be drawn owing to the small sample size. This study represents a starting point for investigating the safety of aripiprazole discontinuation on recurrence in patients with MDD who have achieved remission with AATA. Future studies with appropriate sample sizes calculated based on this study are needed.

Pelvic lymph node involvement and risk of recurrence in HPV-associated endocervical adenocarcinoma stage IA2-IB1 according to Silva's system in two Colombian cancer centers.

To compare the pelvic lymph node involvement and risk of recurrence in patients with human papillomavirus (HPV)-associated endocervical adenocarcinoma stage IA2-IB1 undergoing hysterectomy and/or trachelectomy plus lymphadenectomy, according to Silva's classification system. A retrospective cohort study was performed in two Colombian cancer centers. The cases were classified according to the Silva classification system. Clinical, surgical, and histopathological variables were evaluated. Recurrence risk was analyzed by patterns A, B, or C. A logistic regression model was performed for tumor recurrence. The Kaplan-Meier method was used to estimate overall survival and disease-free survival (DFS). A weighted kappa was performed to determine the degree of concordance between pathologists. A total of 100 patients were identified, 33% pattern A, 29% pattern B, and 38% pattern C. The median follow-up time was 42.5 months. No evidence of lymph node involvement was found in patients classified as A and B, while in the C pattern was observed in 15.8% (n = 6) of cases (P < 0.01). There were 7% of cases with recurrent disease, of which 71.5% corresponded to type C pattern. Patients with Silva pattern B and C had 1.22- and 4.46-fold increased risk of relapse, respectively, compared with pattern A. The 5-year DFS values by group were 100%, 96.1%, and 80.3% for patterns A, B, and C, respectively. For patients with early-stage HPV-associated endocervical adenocarcinoma, the type C pattern presented more lymph node involvement and risk of recurrence compared to the A and B patterns. The concordance in diagnosis of different Silva's patterns by independents pathologists were good.

Abstract 5215: Orphan noncoding RNA (oncRNA) liquid biopsy assay is prognostic for survival in patients with triple-negative breast cancer (TNBC) and residual disease

Abstract Introduction: Residual disease (RD) after neoadjuvant systemic therapy is associated with high recurrence risk in patients with TNBC. oncRNAs are a novel category of small RNAs that are largely absent in healthy tissue but enriched in tumors and can be detected using a blood-based assay. This study investigated impact of an oncRNA recurrence risk model on outcomes in TNBC patients with RD. Methods: Study population included stage I-III TNBC patients with RD and available end-of-treatment (EOT) serum samples who were enrolled in a multisite prospective cohort study. EOT samples were collected after completion of all curative treatment (local/systemic). Small RNAs were isolated from EOT serum, sequenced at average depth of 76.5 ± 12.5 million 50bp single end reads, and annotated using a bespoke bioinformatics pipeline to identify oncRNAs. Cancer risk scores were generated using an oncRNA based tumor detection artificial intelligence model trained on 451 treatment naive breast cancer samples and 470 samples from individuals without known cancer diagnosis. Score cutpoint for high vs low recurrence risk was determined through ROC analysis. Impact of EOT oncRNA risk category on event free survival (EFS) and overall survival (OS) was estimated by Kaplan Meier method and compared by log rank test followed by Cox regression. Residual cancer burden (RCB) was determined according to classification by Symmans et al. Results: oncRNA isolation/score generation was successful for 79 out of 80 TNBC patients with RD and available EOT serum sample. Median age was 48 years and 39% had node positive disease. RCB class distribution was as follows: RCB I=27%, RCB II=49%, RCB III=18%. Training set (n=39) was used to define oncRNA risk score cutpoint. In the testing set (n=40), 38% were classified as oncRNA high-risk and 62% as oncRNA low-risk. oncRNA risk category was not associated with baseline T stage, nodal status, or RCB class. oncRNA high-risk status was associated with lower EFS and OS; 3y EFS was 47% and 73% (HR 2.76, 95% CI 0.92-9.24, p=0.058) and OS 53% and 76% (HR 3.78, 95% CI 1.19-12.00, p=0.016) in high and low risk groups, respectively. In multivariable analysis including oncRNA risk status, T stage, nodal status, and RCB class, oncRNA high risk status retained significant association with lower EFS (HR 7.70, 95% CI 1.33-44.64, p=0.023) and OS (HR 7.99, 95% CI 1.36-47.00, p=0.022). Conclusion: EOT oncRNA liquid biopsy assay was independently prognostic for outcomes in TNBC patients with RD. More than half of patients in the oncRNA high-risk group suffered an EFS event by 3 years. oncRNA risk score has potential to provide prognostic utility complementary to clinicopathologic characteristics in patients with TNBC. These findings should be confirmed in other TNBC studies and may provide insights for patient stratification/selection in RD adjuvant therapy intensification trials. Citation Format: Rachel Yoder, Jennifer Yen, Mehran Karimzadeh, Joshua M. Staley, India Fernandez, Adam C. Heinrich, Fereydoun Hormozdiari, Jeffrey Gregg, Andrew K. Godwin, Irene Acerbi, Raaj Trivedi, Babak Alipanahi, Shane R. Stecklein, Priyanka Sharma. Orphan noncoding RNA (oncRNA) liquid biopsy assay is prognostic for survival in patients with triple-negative breast cancer (TNBC) and residual disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5215.

Assessing risk of recurrent small bowel obstruction after non-operative management in patients with history of intra-abdominal surgery: a population-based comprehensive analysis in Taiwan.

Despite a significant 30% ten-year readmission rate for SBO patients, investigations into recurrent risk factors after non-operative management are scarce. The study aims to generate a risk factor scoring system, the 'Small Bowel Obstruction Recurrence Score' (SBORS), predicting 6-month recurrence of small bowel obstruction (SBO) after successful non-surgical management in patients who have history of intra-abdominal surgery. We analyzed data from patients aged ≥ 18 with a history of intra-abdominal surgery and diagnosed with SBO (ICD-9 code: 560, 568) and were successful treated non-surgically between 2004 and 2008. Participants were divided into model-derivation (80%) and validation (20%) group. We analyzed 23,901 patients and developed the SBORS based on factors including the length of hospital stay > 4 days, previous operations > once, hemiplegia, extra-abdominal and intra-abdominal malignancy, esophagogastric surgery and intestino-colonic surgery. Scores > 2 indicated higher rates and risks of recurrence within 6 months (12.96% vs. 7.27%, OR 1.898, p < 0.001 in model-derivation group, 12.60% vs. 7.05%, OR 1.901, p < 0.001 in validation group) with a significantly increased risk of mortality and operative events for recurrent episodes. The SBORS model demonstrated good calibration and acceptable discrimination, with an area under curve values of 0.607 and 0.599 for the score generation and validation group, respectively. We established the effective 'SBORS' to predict 6-month SBO recurrence risk in patients who have history of intra-abdominal surgery and have been successfully managed non-surgically for the initial obstruction event. Those with scores > 2 face higher recurrence rates and operative risks after successful non-surgical management.

Preventive and therapeutic effects of rifaximin on hepatic encephalopathy with differential application dosages and strategies: a network meta-analysis

BackgroundHepatic encephalopathy (HE) is a neuropsychiatric syndrome that affects the prognosis of patients with liver disease and is considered an independent risk factor for hospitalization and death. Rifaximin has been approved for HE treatment. This review will analyze the effect of rifaximin on different stages of HE with differential application dosages and strategies by traditional and network meta-analyses.MethodsWe performed a systematic search of PubMed, EmBase, and Cochrane Library databases up to February 26, 2023, to identify randomized controlled trials (RCTs) about rifaximin for the prevention and treatment of HE. The outcomes included incidence of HE and HE progression, HE reversal, mortality, and adverse effects.ResultsA total of 21 studies were included. In the primary prevention of HE, rifaximin significantly reduced the incidence of HE (OR: 0.66; 95% CI: 0.45, 0.96; p = 0.032). In secondary prevention, rifaximin significantly reduced the risk of recurrence in patients who were in remission (OR: 0.38; 95% CI: 0.28, 0.52; p < 0.001). In the treatment of minimal HE, rifaximin significantly reduced the breakthrough of MHE to OHE (OR: 0.17; 95% CI: 0.04,0.63; p = 0.008). Rifaximin also significantly improved the clinical symptoms of MHE and OHE patients (OR: 3.76; 95% CI: 2.69, 5.25; p < 0.001). However, rifaximin did not reduce mortality at any stage in HE patients (OR: 0.79; 95% CI: 0.58, 1.08; p = 0.133). Additionally, rifaximin did not increase the risk of adverse effects (OR: 0.96; 95% CI: 0.74, 1.24; p = 0.749). In the network meta-analysis, the 400 mg T.I.D. intervention had a relative advantage for HE risks in primary and secondary prevention. In the treatment of MHE, 600 mg b.i.d. was superior in preventing the breakthrough from MHE to OHE.ConclusionRifaximin prevented HE risks and progression and improved clinical symptoms in patients with MHE but did not reduce mortality. For primary and secondary prevention, 400 mg t.i.d. could be considered. 600 mg b.i.d. could be considered in patients with MHE.

Association of preoperative and postoperative circulating tumour DNA (ctDNA) with PIK3CA gene mutation with risk of recurrence in patients with non-metastatic breast cancer

BackgroundCirculating tumour DNA (ctDNA), contains tumour-specific gene mutation in blood circulation and could aid in postoperative risk stratification of non-metastatic breast cancer. In this study, we investigated the feasibility of detecting PIK3CA gene mutations in ctDNA in the preoperative (preop) and postoperative period (postop), and its prognostic significance in patients with breast cancer. MethodsA cohort of patients with breast cancer undergoing curative surgery with available blood samples preoperatively and postoperatively (PO) at either of PO time point; PO week 1–2, PO week 3–4 and PO weeks 5–12 were enrolled. PIK3CA gene mutations at exons 9 and 20 were detected in ctDNA with High resolution melting (HRM) PCR and Allele specific fluorescence probe-based PCR. ResultsA total of 62 patients (age, median (IQR), 51.50 (45.0–65.0) years), with a median follow-up of 90 months (interquartile range (IQR),60–120 months) were enrolled. In total, 25 (40.3%) and 22 (35%) patients with breast cancer had detectable PIK3CA mutations in ctDNA in preop and postop period, respectively. PIK3CA mutations in ctDNA in postop period (hazard ratio (H.R: 18.05, p = 0.001) were negative prognostic factor for recurrence-free survival (RFS) and overall survival (O·S) (H.R: 11.9, p = 0.01) in patients with breast cancer. Subgroup analysis of ctDNA indicate that positive ctDNA in both preop/postop period and post op period only were found to have prognostic effect on RFS and O·S (RFS; p < 0.0001, O·S; p = 0.0007. Moreover, ctDNA-based detection preceded clinical detection of recurrence in patients with an average lead time of 12.00 months (IQR:20–28.5 months) across all breast cancer subtypes. ConclusionWe highlighted the prognostic ability of ctDNA in patients with breast cancer in perioperative period. However, future prospective studies are needed to assess the utility of ctDNA in breast cancer.

Atypical meningioma: Histopathological, genetic, and epigenetic features to predict recurrence risk.

Grading assessed according to World Health Organization (WHO) criteria is a major prognostic factor for determining the risk of recurrence in patients with meningiomas and establishing the most appropriate therapeutic strategy after surgery. However, the main issue is to predict the recurrence risk of WHO grade 2 meningioma and, more specifically, of the atypical subtype. Indeed, owing to a reported recurrence rate of 50%, either radiotherapy or observation is currently considered an option after gross total surgical resection of atypical meningiomas. These heterogeneous clinical outcomes are likely related to the broad histopathological diagnostic criteria for this subtype, and whether meningiomas only present as brain invasion should be classified as atypical remains controversial. Over the last few years, several studies have shown that DNA methylation profiling, next-generation sequencing, and transcriptomics can better stratify meningiomas for their recurrence risk than histology. The main limitations to the widespread use of these approaches to classify meningiomas are their high cost and the need for sophisticated technologies. However, all studies concurred that atypical meningiomas without chromosome 1p deletion display a low recurrence risk, suggesting that the assessment of this cytogenetic alteration could represent an easy and quick method to determine which patients could benefit from adjuvant treatment after surgery. In addition, prognostically unfavorable molecular groups can be distinguished using specific immunostainings, although further validation is required.

Prognostic Significance of NLR, LMR, PLR, and CRP-Albumin Ratio in Lower Extremity Cellulitis: A Hospitalization and Recurrence Analysis.

Cellulitis, an inflammatory disease of the skin and subcutaneous tissue caused by bacterial agents, frequently causes lower-extremity wounds. Many new biomarkers have been introduced to aid the diagnosis of inflammatory diseases. In this study, we aimed to evaluate the risk of recurrence of lower-extremity cellulitis wounds and the factors determining the need for hospitalization. Demographic characteristics and underlying diseases of the patients, white blood cell count, neutrophil, lymphocyte, monocyte, neutrophil, lymphocyte, lymphocyte and monocyte counts at admission, white blood cell count at admission, platelet count, total protein, albumin, erythrocyte sedimentation rate, C-reactive protein (CRP), procalcitonin level, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and CRP/albumin ratio were evaluated. Of the 132 patients with lower extremity cellulitis wounds, the median age was 56 years (range, 20-96 years), and 88 (66.7%) were male. Diabetes mellitus was the most commonly associated systemic disease. The most common symptom (97%) was a rash. Of the patients, 80 (60.6%) were hospitalized and 52 (39.4%) were treated as outpatients. Seventeen (12.9%) patients had recurrent cellulitis. While comorbidities and increased lesion size increased the risk in patients with recurrent cellulitis, median platelet count (P = .010), D-dimer level (P = .036), and CRP-Alb ratio (P = .019) were higher. Particularly increased lesion size, platelet count, total protein, and CRP levels should be a warning to clinicians in terms of the need for hospitalization and the risk of recurrence in patients with cellulite. In our study, PLR and CRP/albumin ratios were found to be high in these patient groups, and determining the usefulness of new biomarkers through new studies will give us a new perspective in clinical practice.

Association of preoperative muscle-adipose index measured by computed tomography with survival in patients with esophageal squamous cell carcinoma

BackgroundConventional nutritional metrics are closely associated with the prognosis of patients with radically resected esophageal squamous cell carcinoma (ESCC). Nevertheless, the prognostic implications of muscle and adipose tissue composite indexes in ESCC remain unknown.MethodsWe retrospectively analyzed clinicopathological data of 304 patients who underwent resected ESCC. To obtain measurements of the muscle and adipose indexes, preoperative computed tomography (CT) images were used to quantify skeletal-muscle adipose tissue. The diagnostic threshold for muscle-adipose imbalance was determined using X-tile software and used to analyze the association between the muscle-adipose index (MAI) and survival. Instantaneous risk of recurrence was assessed using a hazard function. We constructed a nomogram based on the MAI and other clinical characteristics and established a novel predictive model with independent prognostic factors. The prognostic capabilities of these nomograms were evaluated using calibration curves, receiver operating characteristic (ROC) curves, and decision-curve analysis (DCA).ResultsThe overall survival (OS) and disease-free survival (DFS) rates in the muscle-adipose-balanced group were significantly better than those in the muscle-adipose-imbalanced group. Multivariate analyses revealed that the MAI, prognostic nutritional index (PNI), tumor stage, and tumor differentiation were independent prognostic factors for OS and DFS in patients with resected ESCC (P < 0.05). The nuclear density curve indicated a lower risk of recurrence for patients in the muscle-adipose-balanced group than that for their imbalanced counterparts. Conversely, the nuclear density curve for PNI was confounded. Postoperative radiotherapy- (RT) benefit analysis demonstrated that patients with ESCC in the muscle-adipose-balanced group could benefit from adjuvant RT.ConclusionThis study confirmed that preoperative MAI could serve as a useful independent prognostic factor in patients with resected ESCC. A nomogram based on the MAI and other clinical characteristics could provide individualized survival prediction for patients receiving radical resection. Timely and appropriate nutritional supplements may improve treatment efficacy.

Pregnancy and the disease recurrence of patients previously treated for differentiated thyroid cancer: A systematic review and meta analysis.

Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remains controversial. This study aimed to summarize existing evidence regarding the association of pregnancy with recurrence risk in patients previously treated for DTC. We searched PubMed, Embase, Web of Science, Cochrane, and Scopus based on the prespecified protocol registered at PROSPERO (CRD42022367896). After study selection, two researchers independently extracted data from the included studies. For quantitative data synthesis, we used random-effects meta-analysis models to pool the proportion of recurrence (for pregnant women only) and odds ratio (OR; comparing the risk of recurrence between the pregnancy group and the nonpregnancy group), respectively. Then we conducted subgroup analyses to explore whether risk of recurrence differed by response to therapy status or duration of follow-up time. We also assessed quality of the included studies. A total of ten studies were included. The sample size ranged from 8 to 235, with participants' age at pregnancy or delivery ranging from 28 to 35 years. The follow-up time varied from 0.1 to 36.0 years. The pooled proportion of recurrence in all pregnant patients was 0.13 (95% confidence intervals [CI]: 0.06-0.25; I2 : 0.58). Among six included studies reporting response to therapy status before pregnancy, we observed a trend for increasingly higher risk of recurrence from excellent, indeterminate, and biochemically incomplete to structurally incomplete response to therapy ( Ptrend <0.05). The pooled risk of recurrence in the pregnancy group showed no evidence of a significant difference from that in the nonpregnancy group (OR: 0.75; 95% CI: 0.45-1.23; I2 : 0). The difference in follow-up time (below/above five years) was not associated with either the proportion of recurrence in all pregnant patients ( P >0.05) or the OR of recurrence in studies with a comparison group ( P >0.05). Two included studies that focused on patients with distant metastasis also did not show a significant difference in disease recurrence between pregnancy and nonpregnancy groups (OR: 0.51 [95% CI: 0.14-1.87; I2 : 59%]). In general, pregnancy appears to have a minimal association with the disease recurrence of DTC with initial treatment. Clinicians should pay more attention to progression of DTC among pregnant women with biochemical and/or structural persistence. PROSPERO, https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022367896.