Risk Of Recurrence In Group Research Articles

Prosigna Assay for Treatment Decisions in Early Breast Cancer: A Decision Impact Study.

Introduction: Therapeutic decisions in early breast cancer are based on clinico-pathological features which are subject to intra- and inter-observer variability. This single-center decision impact study aimed to evaluate the effects of the Prosigna assay on physicians' adjuvant treatment choices. Methods: Between 09/2017 and 02/2018, formalin-fixed tumor samples from 52 newly diagnosed, postmenopausal, hormone receptor-positive, HER2-negative breast cancer (T1-T2; pN0-N1a) patients were analyzed. Pre-test clinical judgements and Prosigna test results were compared. Results: The mean age was 59 (42-77). Invasive ductal carcinoma (79.2%), grade 2 (52.8%) and T1c-N0 tumors (43.4%) were represented. There was 40.4% discordance between the pre- and post-test risk of recurrences. No significant change was observed in the clinical intermediate risk category, while there was a net reclassification of low-risk patients into a high Prosigna recurrence risk group. In addition, clinically determined intrinsic subtypes were 34.6% discordant with the Prosigna results, which is largely driven by the reclassification of the luminal A tumors into the Prosigna-assessed luminal B group. Before the Prosigna test, endocrine treatment was the primary choice in 20 patients (39.2%), and chemotherapy was recommended to 31 patients (60.8%). Overall, the Prosigna assay led to a change in treatment choice for one patient. Conclusions: Although conventional risk assessment methods are relatively inexpensive with shorter turnaround times, their accuracy and value for risk reduction are suboptimal. According to our results, the Prosigna assay was found to be a relevant tool for the clinical decision making process. Long-term follow-up of these patients will elucidate the potential benefits of using multigene molecular tests as biomarkers for treatment.

M2BPGi Correlated with Immunological Biomarkers and Further Stratified Recurrence Risk in Patients with Hepatocellular Carcinoma

Introduction Novel biomarkers reflecting liver fibrosis and the immune microenvironment may correlate with the risk of hepatocellular carcinoma (HCC) recurrence. This study aimed to evaluate the prognostic value of serum biomarkers in predicting HCC recurrence. Methods Serum biomarkers, including M2BPGi, IL-6, IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM-3, and LAG-3, were measured in 247 patients with HCC undergoing surgical resection. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were evaluated. The ERASL-post model and IMbrave050 criteria were used to define HCC recurrence risk groups. Results Serum M2BPGi levels significantly correlated with FIB-4 score, APRI, ALBI score, AFP, ALT, AST, IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM-3, and LAG-3 levels. M2BPGi, VEGF-A, soluble PD-1, and TIM-3 levels significantly correlated with RFS. In multivariate analysis, M2BPGi >1.5 COI (hazard ratio (HR) = 2.100, p < 0.001), tumor size >5 cm (HR = 1.859, p = 0.002), multiple tumors (HR = 2.562, p < 0.001), AFP >20 ng/mL (HR = 2.141, p < 0.001), and microvascular invasion (HR = 1.954, p = 0.004) were independent predictors of RFS. M2BPGi levels significantly stratified the recurrence risk in ERASL-post and IMbrave050 risk groups. An M2BPGi-based model could significantly discriminate RFS in the overall cohort as well as in the IMbrave050 low- and high-risk groups. M2BPGi >1.5 COI was also an independent predictor of OS after resection (HR = 2.707, p < 0.001). Conclusion Serum M2BPGi levels significantly correlated with surrogate markers of liver fibrosis, liver function, and immunology. M2BPGi is a significant predictor of HCC recurrence and survival after resection and could be incorporated into recurrence-prediction models.

Prognostic Factors Affecting Recurrence in Peripheral T-Cell Lymphoma Patients with Different HDAC Levels

To analyze the distribution characteristics of prognostic factors affecting recurrence in peripheral T-cell lymphoma (PTCL) patients with different levels of histone deacetylase (HDAC) based on latent class analysis. 112 PTCL patients who were treated in our hospital from September 2012 to September 2019 were selected and divided into recurrence group and non-recurrence group. The clinical data of the two groups of patients were compared. Multivariate logistic regression was used to analyze the risk factors for recurrence. Latent class analysis was used to compare the distribution characteristics of prognostic factors affecting recurrence between the high-risk group and the low-risk group. There were 87 patients (77.68%) in recurrence group and 25 patients (22.32%) in non-recurrence group. The result of multivariate logistic regression showed that ECOG score ≥2, Ann Arbor stage III-IV, IPI score >2, bone marrow involvement, elevated serum β2-microglobulin (β2-MG), short-term efficacy not reaching complete remission (CR) or partial remission (PR), and the high expression of HDAC were all independent risk factors for recurrence in patients with PTCL (P <0.05). The recurrence rate of patients with high HDAC levels was significantly higher than that of patiens with low HDAC levels (P <0.05). The results of cluster analysis showed that the risk of recurrence was obviously clustered, and the patients could be divided into high recurrence risk group (HDAC＞5 points) and low recurrence risk group (HDAC≤5 points). The results of latent class analysis showed that patients with multiple risk factors account for a higher proportion in the high recurrence risk group, compared with the low recurrence risk group (P <0.05). There are differences in recurrence rates among PTCL patients with different HDAC levels and in distribution characteristics of risk factors between high recurrence risk and low recurrence risk groups.

Breast Cancer Index re-stratifies 21-gene assay risk groups for late distant recurrence and extended endocrine therapy benefit: Results from the BCI Registry Study.

529 Background: Patients with hormone receptor-positive (HR+) breast cancer face a prolonged risk for late distant recurrence (DR), even after 5 years of adjuvant endocrine therapy. The BCI (Breast Cancer Index, Biotheranostics) is a genomic assay that provides the risk of late DR and predicts the likelihood of benefit from extended endocrine therapy (EET) based on the H/I (HOXB13/IL-17BR) ratio. The 21-gene RS (Recurrence Score; Oncotype DX, Exact Biosciences) test provides the 9-year risk of DR and the benefit from adjuvant chemotherapy (CT) in HR+/HER2− breast cancer. However, the RxPONDER trial showed that RS was not predictive of CT benefit in premenopausal women with N1 disease. Here, we investigated the concordance between BCI prognostic score and H/I versus RS in HR+/HER2- patients from the BCI Registry study. Methods: The BCI Registry study is a prospective, multi-institutional study to evaluate the long-term clinical outcome, decision impact and medication adherence in early-stage HR+ breast cancer patients. Based on TAILORx and RxPONDER results, RS stratified patients into four risk groups: Age ≤ 50, No CT benefit (RS ≤ 15); Age ≤ 50, CT benefit (RS&gt;15); Age &gt; 50, No CT benefit (RS ≤ 25); and Age &gt; 50, CT benefit (RS &gt; 25). Kendall’s correlation coefficient (R) was used to estimate the correlation between BCI prognostic score, BCI (H/I) and RS as continuous variables. Results: BCI and RS results were reported for 847 patients (76% T1; 59% grade II; 85% N0). H/I classified 559 patients (66%) as H/I-Low and 288 (34%) as H/I-High, respectively, while BCI prognostic risk scores classified 434 patients (51%) as low-risk and 413 (49%) as high-risk for late DR. RS classified 30 patients (4%) as Age ≤ 50, No CT benefit, 38 (5%) as Age ≤ 50, CT benefit, 665 (78%) as Age &gt; 50, No CT benefit and 114 (13%) as Age &gt; 50, CT benefit. When analyzed as continuous variables, BCI H/I and prognostic score showed a weak correlation with RS with R=0.18 and R=0.2, respectively. Based on categorical groups, H/I had low concordance with RS for younger women (Age ≤ 50) but showed some correlation with RS for older women (Age &gt; 50). Among those older than Age 50, H/I identified 31% of those with no CT benefit as likely to benefit from EET while 39% of those with CT benefit as not likely to benefit from EET. Conclusions: BCI H/I and prognostic risk scores exhibited low concordance with RS risk categories. H/I consistently re-stratified RS risk categories into distinct H/I-Low and -High groups, further substantiating that prediction of CT benefit does not equate to prediction of EET benefit. [Table: see text]

Supramarginal resection of skull base chordomas: proof of concept and preliminary outcomes.

The mainstay of treatment for skull base chordoma (SBC) is maximal safe resection followed by radiotherapy. However, even after gross-total resection (GTR), the recurrence rate is high due to microscopic disease in the resection margins. Therefore, supramarginal resection (SMR) could be beneficial, as has been shown for sacral chordoma. The paradigm of postoperative radiation therapy for every patient has also begun to change, as molecular profiling has shown variability in the risk of recurrence. The aim of this study was to present the concept of SMR applied to SBC, along with an individualized decision for postoperative radiation therapy. This is a retrospective analysis of all SBCs operated on by the senior author between 2018 and 2023. SMR was defined as negative histological margins of bone and/or dura mater, along with evidence of bone resection beyond the tumor margins in the craniocaudal and lateral planes on postoperative imaging. Tumors were classified into 3 molecular recurrence risk groups (group A, low risk; group B, intermediate risk; and group C, high risk). Postoperative radiation therapy was indicated in group C tumors, in group B chordomas without SMR, or in cases of patient preference. Twenty-two cases of SBC fulfilled the inclusion criteria. SMR was achieved in 12 (55%) cases, with a mean (range) amount of bone resection beyond the tumor margins of 10 (2-20) mm (+40%) in the craniocaudal axis and 6 (1-15) mm (+31%) in the lateral plane. GTR and near-total resection were each achieved in 5 (23%) cases. Three (19%) tumors were classified as group A, 12 (75%) as group B, and 1 (6%) as group C. Although nonsignificant due to the small sample size, the trends showed that patients in the SMR group had smaller tumor volumes (13.9 vs 19.6 cm3, p = 0.35), fewer previous treatments (33% vs 60% of patients, p = 0.39), and less use of postoperative radiotherapy (25% vs 60%, p = 0.19) compared to patients in the non-SMR group. There were no significant differences in postoperative CSF leak (0% vs 10%, p = 0.45), persistent cranial nerve palsy (8% vs 20%, p = 0.57), and tumor recurrence (8% vs 10%, p = 0.99; mean follow-up 15 months) rates between the SMR and non-SMR groups. In select cases, SMR of SBC appears to be feasible and safe. Larger cohorts and longer follow-up evaluations are necessary to explore the benefit of SMR and individualized postoperative radiation therapy on progression-free survival.

Association of α-SMA and EpCAM Expressions with Recurrence Risk Based on Histopathological Subtypes of Basal Cell Carcinoma

Background Basal cell carcinoma (BCC) is the most common skin malignancy in the world with a proportion 70%. Recurrent and aggressive variants are still challenging in diagnosis and treatment. Histopathologically, there are two group of BCC risk of recurrence, i.e low risk and high risk. Assessment the expression of alpha-smooth muscle actin (α-SMA) as a biomarker of cancer associated fibroblast cell in stroma and the expression of epithelial cell adhesion molecule (EpCAM) in tumor cells probably have role in the pathomechanism of BCC progression, suggest its can distinguish the risk of BCC recurrence. This research aims to determine the assosiation between the expression of α-SMA and EpCAM with the recurrence risk group of BCC histopathological subtypes. Methods This was a cross sectional study using 48 samples, with 24 low and high risk groups each. Histopathological subtypes were determined from Hematoxylin and eosin slide. The expression of α-SMA and EpCAM was examined by the immunohistochemical method which was assessed semiquantitatively. Statistical analysis was performed using the Chi-square test with p&lt;0.05 was considered significant. Results Expression of α-SMA with the score 3 was found more in high risk BCC (85.7%), while a score of 1 was more in low risk BCC (100%). Loss of EpCAM expression was mainly found in high risk BCC (82.8%). Statistical analysis showed that there was a significant assosiation between the expression of α-SMA and EpCAM and the recurrence risk group of BCC histopathological subtypes with p value =0.000 for each. Conclusions This study concluded that increased of α-SMA expression and loss of EpCAM expression were associated with a high recurrence risk group of BCC histopathological subtypes.

ЛАТЕНТНАЯ ТУБЕРКУЛЕЗНАЯ ИНФЕКЦИЯ У ЛИЦ С НАЛИЧИЕМ ОСТАТОЧНЫХ ПОСТТУБЕРКУЛЕЗНЫХ ИЗМЕНЕНИЙ В ОРГАНАХ ДЫХАНИЯ ПО ДАННЫМ КОЖНОЙ ПРОБЫ С ПРЕПАРАТОМ ДИАСКИНТЕСТ®

Aim: to study the prevalence of latent tuberculosis infection (LTI) among individuals with residual post-tuberculosis changes in the lungs and assess the effectiveness of the Diaskintest® for LTI detection. Materials and methods. We carried out a retrospective analysis of results of the skin test with recombinant tuberculosis allergen (RTA), i.e. Diaskintest®, in 181 patients (109 men and 72 women) with residual post-tuberculosis changes in the lungs in 2011–2022. The study did not include household or occupational contacts of active TB patients or HIV-infected individuals. Results. We established LTI in 52.5% of individuals with residual post-tuberculosis changes in the lungs. LTI was common among young men (56%) with history of active TB and TB treatment (69%), and those with large residual changes (57.3%). The frequency of LTI detection in individuals with inactive residual post-tuberculosis changes in the lungs allowed classifying them as high riskgroup for TB recurrence. This group requires dynamic observation including yearly fluorography screening and sputum examination for M. tuberculosis detection. Conclusion. Frequent detection of LTI among individuals with residual post tuberculosis changes in the lungs justifies the use of the Diaskintest® during dynamic follow-up of this group, which is predisposed to TB recurrence.

Survival Predictors Before Preoperative Adjuvant Chemotherapy in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma.

Radical resection after preoperative adjuvant chemotherapy (NAC) is a standard treatment for patients with locally advanced esophageal squamous cell carcinoma (LAESCC), but its outcome remains unsatisfactory. In order to develop a personalized treatment program for LAES, we herein compared the survival prediction utility of five pre-NAC nutritional, inflammatory, and immune indexes in patients with LAESCC. We evaluated the survival of 203 patients with LAESCC who underwent radical resection after NAC from January 2011 to September 2019 for the following representative pre-NAC nutritional, inflammatory, and immune indices: modified Glasgow Prognostic Score, Prognostic Nutritional Index, C-reactive protein/albumin ratio, serum neutrophil/lymphocyte ratio, and Geriatric Nutrition Risk Index (GNRI) were evaluated for their impact on survival. Of the five indices, GNRI was the best predictor of survival as determined by the area under the curve (p<0.05). When patients were divided into three groups according to the nutritional risk assessment of Bouillanne et al. using the pre-NAC GNRI, the 5-year overall survival (OS) and recurrence-free survival (RFS) were significantly stratified (p<0.001). On multivariate analysis, the GNRI independently identified a poor OS group [group 1: hazard ratio (HR)=2.598, p=0.002; group 2: HR=6.257, p<0.001] and a high recurrence risk group (group 1: HR=1.967, p=0.016; group 2: HR=4.467, p<0.001). In patients with LAESCC, GNRI may be the most accurate, reliable, and useful prognostic factor among the five major systemic inflammatory and nutritional indices.

Solitary fibrous tumor: Can the new Huang risk stratification system for orbital tumors improve prognostic accuracy in other tumor locations?

Solitary fibrous tumors (SFTs) are known for their heterogeneous morphology, characterized by a variety of cell shapes and different growth patterns. They can also arise in various anatomical locations, most commonly in extremities and deep soft tissues. Despite this diversity in morphology and location, all SFTs share a common molecular signature involving the NAB2::STAT6 gene fusion. Due to their unpredictable clinical behavior, establishing prognostic factors is crucial. This study aims to evaluate an orbital risk stratification system (RSS) proposed by Huang et al. for use in extraorbital SFTs using a database of 97 cases. The Huang model takes into consideration tumor size, mitotic figures, Ki-67 index, and dominant constituent cell (DCC) as key variables. Survival analysis confirmed the model's predictive value, with higher-risk scores being associated with poorer outcomes. However, in contrast to the orbital SFTs studied by Huang et al., our study did not find a correlation between tumor size and recurrence in extraorbital cases. While the Huang model performs slightly better than other RSS, it falls short on achieving statistical significance in distinguishing recurrence risk groups in extraorbital locations. In conclusion, this study validates the Huang RSS for use in extraorbital SFTs and underscores the importance of considering DCC, mitotic count, and Ki-67 together. However, we found that including tumor size in this model did not improve prognostic significance in extraorbital SFTs. Despite the benefits of this additional RSS, vigilant monitoring remains essential, even in cases classified as low-risk due to the inherent unpredictability of SFT clinical outcomes.

Integrated analysis of tumor and adjacent non-tumor proteomic data reveals SERPINH1 as a recurrence biomarker and drug target in hepatocellular carcinoma.

The high rate of postoperative recurrence contributes to the poor outcome in hepatocellular carcinoma (HCC), and effective strategies for managing recurrence are currently lacking. Based on seven pairs of tumors and non-tumor adjacent tissues (NATs) proteomic datasets across five cancer types, this study systematically investigates the stratified and therapeutic value of tumors and NATs for tumor recurrence. NATs exhibited stable and irreplaceable independent prognostic capabilities for recurrence, complementing clinical indicators and tumor characteristics. In comparison to tumor tissues, NATs exhibit higher enrichment levels of recurrence-related proteins in pathways such as immunity, extracellular matrix, and angiogenesis. Taking HCC as an example, we identified SERPINH1 as a recurrent biomarker with drug-targeting potential that applied to both tumors and NATs and then validated them through independent immunohistochemistry cohorts and animal experiments. Patients with high SERPINH1 expression in both tumors and NATs have the highest 5-year recurrence rates, even among clinically low recurrence risk groups. Targeting SERPINH1 can effectively delay tumor occurrence and progression. This study highlights the significant importance of NATs in recurrence prediction and postoperative management, proposing a recurrence management strategy that focuses on both tumors and NATs. SERPINH1 emerges as a valuable biomarker and drug target for addressing postoperative recurrence in HCC.

HER2 positivity predicts BCG unresponsiveness and adaptive immune cell exhaustion in EORTC risk-stratified cohort of bladder cancer.

Predicting the response to Bacillus Calmette-Guérin (BCG) therapy in high-risk patients with non-muscle invasive bladder cancer (NMIBC) is crucial, as failure may necessitate interventions, such as radical cystectomy or salvage therapy. With the recent classification of genetic class 2a (which has HER2 protein abundance as its signature mutation of ERBB2), evaluating its prognostic role and relationship with BCG response could yield important results. This retrospective study included 160 patients with NMIBC who underwent transurethral resection of bladder tumors at Gangneung Asan Hospital between 2000 and 2013 and were stratified based on the European Organization for Research and Treatment of Cancer (EORTC) risk criteria. In addition, we analyzed a subset of 67 patients who had received BCG induction therapy to identify factors predictive of BCG treatment response. Univariate and multivariate analyses were used to assess the impact of clinicopathological factors, HER2 positivity, and EORTC risk on recurrence, progression, survival, and BCG response. Each variable's prognostic significance was determined using the Kaplan-Meier analysis. The tumor microenvironments (TMEs) were evaluated in relation to HER2 and EORTC risk. Patients with HER2+ had a higher median age, a greater prevalence of high-grade tumors, and more frequent recurrences. The univariate analysis demonstrated that the HER2+, intermediate (vs. low-risk) high (vs. low-risk), and EORTC recurrence risk groups were significantly associated with recurrence. In patients treated with BCG, only the HER2+ status predicted recurrence. In the univariate analysis for progression, age, high EORTC progression risk (vs. low-to-intermediate), HER2+, and programmed death-ligand 1 positive (PD-L1+) were significant factors. In multivariate analyses for progression, age, high EORTC progression risk, and PD-L1+ were significant factors for progression. HER2 expression was associated with the TME, influencing the proportion of PD-L1+ cells, as well as other markers of PD-1, CD8, and Ki67. The HER2+ status may be related to genetic characteristics that appear more frequently in older age, which suggests a potential for predicting the recurrence and response to BCG treatment. Additionally, analyzing TME trends of aggressive adaptive immune response characterized by HER2 expression provides insight into recurrence and BCG response mechanisms.

EAU Biochemical Recurrence Risk Classification and PSA Kinetics Have No Value for Patient Selection in PSMA-Radioguided Surgery (PSMA-RGS) for Oligorecurrent Prostate Cancer.

To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen (PSMA-RGS). Currently, neither BCR risk group nor PSA doubling time (PSA-DT), or PSA velocity (PSA-V) are actively assigned or relevant for counseling prior to PSMA-RGS. We retrospectively analyzed PSMA-RGS cases for oligorecurrent prostate cancer between 2014 and 2023. BCR risk groups, PSA-DT, and PSA-V were analyzed as predictors for complete biochemical response (cBR, PSA < 0.2 ng/mL), BCR-free, and therapy-free survival (BCRFS, TFS). Of 374 included patients, only 21/374 (6%) and 201/374 (54%) were classified as low- and high-risk BCR (no group assignment possible in 152/374, 41%). A total of 13/21 (62%) patients with low- and 120/201 (60%) with high-risk BCR achieved cBR (p = 1.0). BCR classification was no predictor for BCRFS (HR:1.61, CI: 0.70-3.71, p = 0.3) or subsequent TFS (HR:1.07, CI: 0.46-2.47, p = 0.9). A total of 47/76 (62%) patients with PSA-DT ≤ 6 mo and 50/84 (60%) with PSA-DT > 6 mo achieved cBR (p = 0.4). PSA-DT was not associated with cBR (OR: 0.99, CI: 0.95-1.03, p = 0.5), BCRFS (HR: 1.00, CI: 0.97-1.03, p = 0.9), or TFS (HR: 1.02, CI: 0.99-1.04, p = 0.2). Consistent negative findings were recorded for PSA-V. The BCR risk groups and PSA kinetics do not predict the oncological success of PSMA-RGS performed at low absolute PSA values. Indolent low-risk BCR is rarely treated by PSMA-RGS.

Molecular landscape and clinical significance of exon 11 mutations in KIT gene among patients with gastrointestinal stromal tumor: a retrospective exploratory study.

This aim of this study was to investigate the prognostic significance of KIT exon 11 mutation subtypes in patients with GISTs. A total of 233 consecutive patients diagnosed with GISTs at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2018 were included in this study. The prevalence and mutation landscape of exon 11 in KIT was presented. The clinicopathological characteristics and prognosis among the different mutation subtypes were analyzed. All the statistical analyses were performed by SPSS22.0. Somatic mutational analysis indicated that point mutations were the most frequently detected mutations followed by deletions & compound mutations and insertion and tandem duplication mutations in the stomach. Point mutations showed a low mitotic count and a high risk of recurrence, and deletions and compound mutations have a high mitotic count while insertions and tandem duplication mutations showed a low mitotic count with an intermediate recurrence risk. Point mutations and deletions frequently occurred in sequence region codons 550-560 of exon 11, while compound mutations, insertion, and tandem duplication were mainly detected in codons 557-559, 572-580, and 577-581, respectively. The multi-variation analysis demonstrated that tumor diameter and high recurrence risk groups had worse prognostic values. However, mutation types were not significant predictors of relapse-free survival (RFS) in GISTs. Survival analysis suggested no significant difference in RFS between the 557/558 deletion and the other deletions. This study suggested that mutations in exon 11 of the KIT gene were common with intermediate/high recurrence risk in GISTs patients. Tumor diameter ≥5 cm, and deletions mutations might predict a worse prognosis.

Global Antiphospholipid Syndrome Score (GAPSS) in Patients with Systemic Lupus Erythematosus

The Global Antiphospholipid Syndrome Score (GAPSS) is a tool proposed to quantify the risk of clinical manifestations associated with antiphospholipid antibodies (aPL) and certain cardiovascular risk factors. To validate GAPSS in a cohort of patients with systemic lupus erythematosus in Russia. 115 patients with SLE were included in the study, including 51 (44%) patients with systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS), 14 (12%) SLE patients with aPL, and 50 (44%) patients with SLE. There was a history of thrombosis in 58 (50%) out of 115 patients; of them, 14 (24%) had arterial thrombosis, 29 (50%) had venous thrombosis, and 15 (26%) had combined thrombosis. Pregnancy against the background of the disease occurred in 43 women included in the study. Of them, 29 (67%) had obstetric pathology. Patients with thrombosis and obstetric pathology had a GAPSS score of 7.17 ± 5.64 versus 4.48 ± 4.55 without these manifestations (p = 0.0003). There was a significant association between GAPSS levels and thrombosis: patients with thrombosis had a GAPSS of 7.31 ± 5.70, those without thrombosis—4.00 ± 4.81 (p = 0.001). GAPPS values were higher in arterial thrombosis compared to venous thrombosis (10.40 ± 25.30 versus 5.82 ± 5.28, p = 0.01). GAPSS levels ≥ 6 and ≥10 were analyzed to select GAPSS values at which a high risk of recurrent thrombosis and/or obstetric pathology could be indicated. All GAPSS levels had a significant association with clinical manifestations of APS. The quality of GAPSS by ROC analysis showed an area under the curve (AUC) for GAPSS of 0.697. GAPSS can be used to assess the risk of recurrence or development of thrombosis and/or obstetric pathology in patients with SLE in the Russian Federation. The GAPSS ≥6 values should be used to stratify patients with SLE into high risk group for recurrence of vascular complications. Further prospective follow-up is needed to confirm the value of GAPSS.

Role of tumor volume in endometrial cancer: An imaging analysis and prognosis significance.

To evaluate the prognostic value of tumor volume on preoperative MRI in endometrial cancer (EC) patients and its association with adverse prognostic factors and survival. A retrospective observational study with 127 consecutive patients with endometrioid EC was carried out between 2016 and 2021 at Juan Ramón Jiménez University Hospital, Huelva (Spain). All patients underwent preoperative magnetic resonance imaging (MRI) for local staging. The tumor volume was analyzed on MRI by two different methods: by measuring the three maximum diameters of the tumor according to an ellipse formula and by manual region of interest in different sections; the ratio between tumor volume and uterus volume was also calculated as a third tool. The relationships between volume, prognostic factors, and survival were analyzed. A total of 127 patients with endometroid EC underwent preoperative MRI and were included in the study. Tumor volume was significantly higher for deep myometrial invasion, cervical stromal involvement, infiltrated serosa, lymph node metastases, high-grade EC, and lymphovascular space involvement, advanced FIGO stage, and High Recurrence Risk Group (P < 0.001). ROC curves showed that tumor volume greater than 25 cm3 predicts lymph node metastases. Volume index greater than 17 cm3 was associated with reduced disease-free survival (P < 0.001) and overall survival (P < 0.003). Multivariate analysis showed that the greatest tumor volume had an independent impact on recurrence (odds ratio [OR]1.019, 95% confidence interval [CI] 1.005-1.032) and survival (OR 1.027, 95% CI 1.009-1.046). This study shows an important correlation between tumor volume on MRI and poor prognostic factors. Preoperative tumor volume on MRI is a valuable biomarker to be considered for management of EC.

Detection of methylation-based prognostic signatures in liquid biopsy specimens from patients with meningiomas.

2073 Background: Detection of distinct epigenetic biomarkers in circulating cell-free DNA (cfDNA) of liquid biopsy (LB) specimens (e.g. blood) fosters opportunity for prognostication of central nervous system (CNS) tumors and has not been thoroughly explored in patients with meningiomas. Methods: We profiled the cfDNA methylome (EPIC array) in serum from patients with meningiomas (MNG; n = 93) and harnessed internal and external meningioma tissue methylome data with reported follow up (n = 77). To predict recurrence risk (RR), we consolidated a tissue cohort with at least 5 years of follow up and divided them into confirmed recurrence (CR; either reported progressive disease in post-surgical imaging, or additional resections following initial surgery) and confirmed no-recurrence (CNR: no confirmed disease progression w/in at least 5-years of follow-up). Then through application of an iterative process consisting of multiple tissue- and serum-based supervised analyses, we identified risk-specific methylation markers with potential for serum application. which, when inputted into a random forest algorithm allowed for segregation of both tumor tissue and liquid biopsy specimens according to recurrence risk. We estimated immune cell composition using MethylCIBERSORT, where a reference methylome atlas of chosen immune cell types was utilized to deconvolute the MNG samples. Results: The resulting recurrence risk classifier demonstrated an appreciable predictive power in classifying samples as high or low recurrence risk across the tumor tissue cohort (ACC: 87.7%, CUI+: 86.4%). When compared to another classifier of rivaling purpose, our model demonstrated statistically significant agreement across primary meningioma samples (κ = 0.269, p = 0.01), and more accurately predicted samples to recur across expanded time windows (time to recurrence &gt; 5 yrs). Across resulting liquid biopsy classifications, recurrence risk subgroups were analogous with reported risk factors, including WHO grade, extent of resection, and tumor location. Recurrence risk subgroups also demonstrated differential estimated immune cell contributions, with low-risk samples exhibiting a “hot” profile, or enrichment of B-Cells, CD56- and CD4 T-Cells, and natural killer cells. Notably, the estimated neutrophil to lymphocyte ratio, previously purported to be relevant to tumor prognosis, was appreciably higher for those meningioma samples with the highest recurrence risk. Conclusions: DNA methylation markers identified in the serum are suitable for the development of machine learning-based models which present high predictive power to prognosticate patients with meningioma and estimate a differential immune profile across recurrence risk groups. After validation in an external cohort, this noninvasive approach may improve the presurgical therapeutic management of patients with meningiomas.

Peering through the PSMA PET Lens: The Role of the European Association of Urology Biochemical Recurrence Risk Groups after Radical Prostatectomy.

(1) Background: The European Association of Urology (EAU) biochemical recurrence (BCR) risk grouping relies on data from historical cohorts that used conventional imaging techniques. In the era of PSMA PET/CT, we compared the patterns of positivity in the two risk groups and provided insight into positivity predictive factors. (2) Methods: Data from 1185 patients who underwent 68Ga-PSMA-11PET/CT for BCR was analyzed, out of which 435 patients treated initially treated by radical prostatectomy were included in the final analysis. (3) Results: A significantly higher rate of positivity in the BCR high-risk group was observed (59% vs. 36%, p < 0.001). BCR low-risk group demonstrated more local (26% vs. 6%, p < 0.001) and oligometastatic (100% vs. 81%, p < 0.001) recurrences. The BCR risk group and PSA level at the time of PSMA PET/CT were independent predictive factors of positivity. (4) Conclusions: This study confirms that the EAU BCR risk groups have different rates of PSMA PET/CT positivity. Even with a lower rate in the BCR low-risk group, oligometastatic disease was 100% in those with distant metastases. Given the presence of discordant positivity and risk classification, integrating PSMA PET/CT positivity predictors into risk calculators for BCR might improve patient classification for subsequent treatment options. Future prospective studies are still needed to validate the above findings and assumptions.

90-Days Outcomes In Patients With Minor Strokes Or Transient Ischemic Attacks Discharged On Single Vs Dual Anti Platelet-Therapy In the Middle East (P7-5.019)

<h3>Objective:</h3> To compare the 90-day outcome in patients with minor stroke (MIS) or transient ischemic attack (TIA) who were discharged on single versus dual anti-platelet therapy after index event in the multiethnic Middle Eastern community. <h3>Background:</h3> Recent studies have shown that dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke (MIS) or transient ischemic attack (TIA). However, there is paucity of data from middle east regarding role of such intervention and outcome of these patients <h3>Design/Methods:</h3> We inquired all Ischemic stroke and TIA patients from our prospectively collected stroke database admitted since January 2014. We separated them into two groups-discharged on single(SAP) vs DAPT. High risk group for recurrence was defined as patients with ABCD2 score of ≥ 4 or more and NIHSS ≤ 3 at index event. We assessed the outcome as measured with modified Rankin Score (mRS), recurrent ischemic stroke, and other vascular events. <h3>Results:</h3> The data provided yielded 1357 (16.8%) patients with TIAs and 6725 (83.2%) with MIS. Of these only 35% (1481/4219) of high risk patient were discharged on DAPT (38.5% of TIA patients and 30.0% MIS patients). DAPT was initiated within 24 hours of arrival at hospital in 86.3% of patients (p&lt;0.001) with a mean duration of 12.5 ±15.6 hours (p&lt;0.001). Poor outcome (mRS 3–6) (27.9% vs 15.1%, p&lt;0.001), and increased mortality (2.2% vs 1.1%, p&lt;0.001) was more significant in patients discharged on SAP versus DAPT. <h3>Conclusions:</h3> The rates of DAPT in patients with TIA and MIS is low. Patients with high risk TIA and MIS discharged on DAPT has better outcome at 90-days in ethnically diverse group of patients in the Middle East. <b>Disclosure:</b> Ms. Naveed has nothing to disclose. Dr. Akhtar has nothing to disclose. Dr. Shuaib has nothing to disclose. Dr. Al Jerdi has nothing to disclose.

Abstract P2-11-05: Effects of Intrinsic Subtypes and 21-gene Assay on the Early and Late Recurrence Risks in Patients with Early Stage HER2+ Breast Cancer: An Analysis of the North Central Cancer Treatment Group (NCCTG) N9831 (Alliance) Trial

Abstract Background: We previously demonstrated that intrinsic subtypes were associated with prognosis for early recurrence risk in patients (pts) with early-stage HER2-positive (HER2+) BC treated with trastuzumab (H) in the N9831 trial. Here, we evaluated the prognostic value of Intrinsic subtypes and 21-gene assay and the risk of early and late recurrence in the N9831 trial. Methods: NanoString custom code set, which included PAM50 and housekeeping genes, was used to quantify mRNA and generated intrinsic subtypes and risk of recurrence (ROR) score from the N9831 trial in Arms A and C: Arm A chemotherapy alone and arm C concurrent H. Quantitative RT-PCR of 21 genes, calculation of the axis, including estrogen axis (ER, PGR, BCL2, SCUBE2), HER2 axis (GRB7, HER2), proliferation axis (Ki67, STK15, Survivin, CCNB1, MYBL2), invasion axis (MMP11, CTSL2), and recurrence score (RS) risk group assignment (RS group 1 and 2: RS &amp;lt; 31 and RS group 3: RS ≥ 31) were performed using Oncotype DX assay. Cox regression models for RFS were used for analysis. Early recurrence was defined as a recurrence that occurred at ≤ 5 years, and late recurrence was defined as recurrence at &amp;gt; 5 years. Results: A total of 783 patients (Arm A 409 and Arm C 374) were included in this analysis. Using multivariate Cox regression analysis to evaluate the risk of early recurrence in patients who received chemotherapy alone in arm A, both invasion genes (MMP11 HR 1.23, 95%CI 1.05-1.44, p 0.01 and CTSL2 HR 1.36, 95%CI 1.1-1.69, p 0.005) and invasion axis (HR 1.64, 95%CI 1.26-2.13, p &amp;lt; 0.001) were associated with a higher rate of early recurrence. CD68 was associated with improved outcomes (HR 0.56, 95%CI 0.38-0.83, p 0.004). For the risk of early recurrence in patients treated with trastuzumab in arm C, ER (HR 0.85, 95%CI 0.74-0.97, p 0.02), PR (HR 0.78, 95%CI 0.64-0.94, p 0.008), and estrogen axis (HR 0.7, 95%CI 0.57-0.87, p 0.001) were associated with improved outcomes. Invasion axis (HR 1.61, 95%CI 1.08-2.41, p 0.02), Oncotype Dx risk group (3 vs. 1 and 2, HR 8.89, 95%CI 1.27-1124, p 0.02), and basal subtype (HR 2.77, 95%CI 1.1-5.95, p 0.03) were also significantly associated with worse outcomes. For risk of late recurrence, in arm A, ER (HR 1.22, 95%CI 1.04-1.44, p 0.02), PR (1.26, 95%CI 1.05-1.5, p 0.01), and estrogen axis (1.39, 95%CI 1.09-1.77, p 0.008) were associated with worse outcomes. Oncotype Dx risk group (3 vs. 1 and 2, HR 0.4, 95%CI 0.16-0.98, p 0.05) was associated with improved outcomes. However, neither individual gene, axis, nor intrinsic subtypes were associated with the risk of late recurrence in patients treated with trastuzumab. Conclusions: For risks of early recurrence, the invasion genes/axis were associated with increased risks of recurrence in patients with early-stage HER2+ BC regardless of trastuzumab treatment. Among patients treated with trastuzumab, ER genes/axis, Oncotype Dx risk group, and intrinsic subtype were prognostic for risks of recurrence in the first five years. For risks of late recurrence, ER genes/axis and Oncotype Dx risk group were prognostic but only in patients treated with chemotherapy alone. The ER genes/axis were associated with less recurrence in the first five years but worse after five years, reflecting a higher risk of late recurrence in ER/PR+ HER2+ BC patients treated with chemotherapy alone. However, none of the individual gene, axis, or intrinsic subtypes were associated with the risk of late recurrence in patients treated with trastuzumab. Therefore, future studies are needed to identify biomarkers for the risk of late recurrence in HER2+ BC patients treated with adjuvant trastuzumab. Support: BCRF-19-161; U10CA180821, U10CA180882, Genentech. https://acknowledgments.alliancefound.org; Clinicaltrials.gov Identifier: NCT00005970 Citation Format: Saranya Chumsri, Zhuo Li, Nadine Norton, Alvaro Moreno-Aspitia, Gerardo Colon-Otero, Keith L. Knutson, Antonio C. Wolff, Edith A. Perez, E. A. Thompson. Effects of Intrinsic Subtypes and 21-gene Assay on the Early and Late Recurrence Risks in Patients with Early Stage HER2+ Breast Cancer: An Analysis of the North Central Cancer Treatment Group (NCCTG) N9831 (Alliance) Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-05.

European Association of Urology biochemical recurrence risk groups after radical prostatectomy: External validation and identification of independent risk factors for progression and death

BackgroundThe EAU proposed a progression and death risk classification in patients with biochemical recurrence after radical prostatectomy (PR). ObjectiveTo validate the EAU BCR-risk classification in our setting and to find factors related to progression and death. Material and methodsMulticenter, retrospective, observational study including 2140 patients underwent RP between 2011 and 2015. Patients with BCR were identified and stratified in low risk (PSA-DT >1yr and pGS <8) or high-risk (PSA-DT ≤1yr or pGS ≥8) grouping. PSA and metastatic free survival (PSA-PFS, MFS), cancer specific survival (CSS) and overall survival (OS) were calculated (Kaplan Meier curves and log-rank test). Independent risk factors were identified (Cox regression). Results427 patients experienced BCR (32.3% low-risk and 67.7% high-risk). Median PSA-PFS was 135,0 mo (95% CI 129,63-140,94) and 115,0 mo (95% CI 104,02-125,98) (p<0,001), for low and high-risk groups, respectively. There were also significant differences in MFS and OS. The EAU BCR risk grouping was independent factor for PSA-progression (HR 2.55, p 0.009). Time from PR to BCR, was an independent factor for metastasis onset (HR 0.43, 95% CI 0.18−0.99; p 0.044) and death (HR 0.17, 95% CI 0.26.0.96; 23 p 0.048). Differences in MFS (p 0.001) and CSS (p 0.004) were found for <12, ≥12–<36 and ≥36 months from PR to BCR. Others independent factors were early salvage radiotherapy and PSA at BCR. ConclusionsHigh-risk group is a prognostic factor for biochemical progression, but it has a limited accuracy on MP and death in our setting. The inclusion of other factors could increase its predictive power.