Risk Of Recurrence In Patients Research Articles

AB003. SOH22ABS024. Assessment of preoperative and postoperative circulating cell free tumour DNA (ctDNA) can predict risk of recurrence in patients with nonmetastatic breast cancer

Background: Postoperative risk stratification in nonmetastatic breast cancer presents ongoing challenges. Circulating tumour DNA (ctDNA) contains tumour-specific gene mutations detectable in the blood of patients with breast cancer. In this study, we investigated the feasibility of High-Resolution Melting (HRM) PCR technology for detecting PIK3CA mutations in preoperative and postoperative blood samples and its prognostic significance in patients with breast cancer.

Longitudinal Variations of CDC42 in Patients With Acute Ischemic Stroke During 3-Year Period: Correlation With CD4+ T Cells, Disease Severity, and Prognosis.

ObjectiveCell division cycle 42 (CDC42) modulates CD4+ T-cell differentiation, blood lipids, and neuronal apoptosis and is involved in the pathogenesis of acute ischemic stroke (AIS); however, the clinical role of CDC42 in AIS remains unanswered. This study aimed to evaluate the expression of CDC42 in a 3-year follow-up and its correlation with disease severity, T helper (Th)1/2/17 cells, and the prognosis in patients with AIS.MethodsBlood CDC42 was detected in 143 patients with AIS at multiple time points during the 3-year follow-up period and in 70 controls at admission by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, blood Th1, Th2, and Th17 cells and their secreted cytokines (interferon-γ (IFN-γ), interleukin-4 (IL-4), and interleukin-17A (IL-17A)) in patients with AIS were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively.ResultsCompared with controls (p < 0.001), CDC42 was reduced in patients with AIS. CDC42 was negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score (p < 0.001), whereas, in patients with AIS (all p < 0.050), it was positively associated with Th2 cells and IL-4 but negatively correlated with Th17 cells and IL-17A. CDC42 was decreased from admission to 3 days and gradually increased from 3 days to 3 years in patients with AIS (P<0.001). In a 3-year follow-up, 24 patients with AIS recurred and 8 patients died. On the 3rd day, 7th day, 1st month, 3rd month, 6th month, 1st year, 2nd year, and 3rd year, CDC42 was decreased in recurrent patients than that in non-recurrent patients (all p < 0.050). CDC42 at 7 days (p = 0.033) and 3 months (p = 0.023) was declined in reported deceased patients than in survived patients.ConclusionCDC42 is used as a biomarker to constantly monitor disease progression and recurrence risk of patients with AIS.

Iodine Maps from Dual-Energy CT to Predict Extrathyroidal Extension and Recurrence in Papillary Thyroid Cancer Based on a Radiomics Approach.

Accurate prediction of extrathyroidal extension and subsequent recurrence is crucial in papillary thyroid cancer clinical management. Our aim was to conduct iodine map-based radiomics to predict extrathyroidal extension and to explore its prognostic value for recurrence-free survival in papillary thyroid cancer. A total of 452 patients with papillary thyroid cancer were retrospectively recruited between June 2017 and June 2020. Radiomics features were extracted from noncontrast images, dual-phase mixed images, and iodine maps, respectively. Random forest and least absolute shrinkage and selection operator (LASSO) were applied to build 6 radiomics scores (noncontrast radiomics score_random forest; noncontrast rad-score_LASSO; mixed rad-score_random forest; mixed rad-score_LASSO; iodine radiomics score_random forest; iodine radiomics score_LASSO) respectively. Logistic regression was used to construct 6 radiomics models incorporating 6 radiomics scores with clinical risk factors and to compare them with the clinical model. A radiomics model that achieved the highest performance was presented as a nomogram and assessed by discrimination, calibration, clinical usefulness, and prognosis evaluation. Iodine radiomics scores performed significantly better than mixed radiomics scores. Both of them outperformed noncontrast radiomics scores. Iodine map-based radiomics models significantly surpassed the clinical model. A radiomics nomogram incorporating size, capsule contact, and iodine radiomics score_random forest was built with the highest performance (training set, area under the curve = 0.78; validation set, area under the curve = 0.84). Stratified analysis confirmed the nomogram stability, especially in group negative for CT-reported extrathyroidal extension (area under the curve = 0.69). Nomogram-predicted extrathyroidal extension risk was an independent predictor of recurrence-free survival. A high risk for extrathyroidal extension portended significantly lower recurrence-free survival than low risk (P < .001). Iodine map-based radiomics might be a supporting tool for predicting extrathyroidal extension and subsequent recurrence risk in patients with papillary thyroid cancer, thus facilitating clinical decision-making.

Prognostic Factors for Recurrence in Pituitary Adenomas: Recent Progress and Future Directions.

Pituitary adenomas (PAs) are benign lesions; nonetheless, some PAs exhibit aggressive behaviors, which lead to recurrence. The impact of pituitary dysfunction, invasion-related risks, and other complications considerably affect the quality of life of patients with recurrent PAs. Reliable prognostic factors are needed for recurrent PAs but require confirmation. This review summarizes research progress on two aspects—namely, the clinical and biological factors (biomarkers) for recurrent PAs. Postoperative residue, age, immunohistological subtypes, invasion, tumor size, hormone levels, and postoperative radiotherapy can predict the risk of recurrence in patients with PAs. Additionally, biomarkers such as Ki-67, p53, cadherin, pituitary tumor transforming gene, matrix metalloproteinase-9, epidermal growth factor receptor, fascin actin-bundling protein 1, cyclooxygenase-2, and some miRNAs and lncRNAs may be utilized as valuable tools for predicting PA recurrence. As no single marker can independently predict PA recurrence, we introduce an array of comprehensive models and grading methods, including multiple prognostic factors, to predict the prognosis of PAs, which have shown good effectiveness and would be beneficial for predicting PA recurrence.

Effect of Lipoprotein(a) on Stroke Recurrence Attenuates at Low LDL-C (Low-Density Lipoprotein) and Inflammation Levels.

Lp(a) (lipoprotein(a)) contributes to cardiovascular disease mainly through proatherogenic and proinflammatory effects. Here, we aimed to evaluate whether a residual stroke risk of Lp(a) would remain when the LDL-C (low-density lipoprotein cholesterol) and inflammatory levels are maintained low. This prospective cohort study included 9899 patients with ischemic stroke or transient ischemic attack from the Third China National Stroke Registry who had measurements of plasma Lp(a) and were followed up for 1 year. Cutoffs were set at the 50 mg/dL for Lp(a). LDL-C was corrected for Lp(a)-derived cholesterol (LDL-Cc [LDL-C corrected]) and cutoffs were set at 55 and 70 mg/dL.The threshold values of IL-6 (interleukin 6) and hsCRP (high-sensitive C-reactive protein) were the median 2.65 ng/L and 2 mg/L. Multivariable-adjusted hazard ratio (HR) were calculated using Cox regression models for each category to investigate the associations of Lp(a) with stroke recurrence within 1 year. Among all patients, those with Lp(a) ≥50 mg/dL were at higher stroke recurrence risk than those with Lp(a) <50 mg/dL (11.5% versus 9.4%; adjusted HR, 1.20 [95% CI, 1.02-1.42]). However, the risk associated with elevated Lp(a) was attenuated in patients with LDL-Cc <55 mg/dL (high Lp(a) versus low Lp(a): 8.9% versus 9.0%; adjusted HR, 0.92 [95% CI, 0.65-1.30]) or IL-6 <2.65 ng/L (9.0% versus 7.8%; adjusted HR, 1.14 [95% CI, 0.87-1.49]). Notably, in the group with both low LDL-Cc and inflammation levels, the rate of patients with high Lp(a) did not significantly different from the rate of patients with low Lp(a; LDL-Cc <55 mg/dL and IL-6 <2.65 ng/L: 6.2% versus 7.1%; adjusted HR, 0.86 [95% CI, 0.46-1.62]; LDL-Cc <55 mg/dL and hsCRP <2 mg/L: 7.7% versus 7.6%; adjusted HR, 0.97 [95% CI, 0.57-1.66]). However, there was no interaction between the LDL-Cc, IL-6, hsCRP, and Lp(a) levels on stroke recurrence risk. Increased Lp(a) was significantly associated with stroke recurrence risk in patients with ischemic stroke/transient ischemic attack. However, at low LDL-Cc or IL-6 levels, the elevated Lp(a) -associated stroke recurrence risk was attenuated in a secondary prevention setting.

Predictors of Recurrence in Patients with Papillary Thyroid Carcinoma: Does Male Sex Matter?

Simple SummaryMen with papillary thyroid carcinoma tend to have more high-risk features for recurrence than women. However, the prognostic impact of sex remains controversial and unestablished. Our study of 1252 patients indicated that men had risk of recurrence comparable to that of women, although male sex was associated with more aggressive disease. Furthermore, we also confirmed that the impact of sex for recurrence was not associated with tumor size or patient age. In conclusion, male sex did not increase the risk of recurrence in patients with papillary thyroid carcinoma. Male patients do not always require aggressive treatment and follow-up approaches.Male patients with papillary thyroid carcinoma (PTC) usually have aggressive clinicopathological features, including large tumor size and lymph node metastasis; however, it is unclear whether male sex increases the risk of recurrence. Here, we evaluated the effect of sex on disease-free survival (DFS) of patients with PTC. Between 2009 and 2016, 1252 patients who underwent total thyroidectomy for PTC were enrolled; 157 (12.5%) were male and 1095 (87.5%) were female. With a mean follow-up of 6.6 years, five-year DFS rates were comparable between male and female patients (94.9% vs. 96.9%; p = 0.616) after adjusting for potential confounders. Multivariate Cox regression analysis also demonstrated that male sex was not an independent risk factor for recurrence (HR 1.982, 95% CI 0.831–4.726). Subgroup analyses further indicated that both male and female sex—in terms of their associations with five-year DFS—were comparable with other variables, including age < 55 years (94.5% vs. 97.3%; p = 0.520) and tumor size > 1 cm (91.9% vs. 97.0%; p = 0.243). In conclusion, male sex was not associated with the risk of recurrence in patients with PTC. Male patients do not always require aggressive treatment and follow-up approaches.

Nontraditional Risk Factors for Residual Recurrence Risk in Patients with Ischemic Stroke of Different Etiologies

Background and Objective: With the popularization of guideline-based secondary prevention based on traditional risk factors, rates of stroke recurrence reduced greatly after ischemic stroke (IS) or transient ischemic attack (TIA), but the residual risk still exists. We aim to evaluate which IS subtype benefits the most from the current secondary prevention and to evaluate nontraditional risk factors for residual recurrence risk of different IS etiologies. Methods: The study included IS/TIA patients who participated in both biomarker substudy and imaging substudy of the Third China National Stroke Registry. We used 5 guideline-recommended interventions (antiplatelet, statins, anticoagulant, antihypertensive, and antidiabetic therapies) to document the performance of secondary prevention care. Residual risk was defined as the risk of stroke recurrence despite adherence to these 5 guideline-based secondary prevention strategies. Risk factors associated with stroke recurrence were analyzed by using Cox regression models. Results: In total, 9,733 patients were included in this study. At 3 months, 4,186 (43.0%) patients adhered to 5 secondary prevention strategies, and the residual risk of recurrence was 5.1%. According to Trial of Org 10172 in Acute Stroke Treatment subtypes, cardioembolism benefited the most from current secondary prevention (relative risk reduction: 65.2%), followed by large-artery atherosclerosis (LAA) (29.0%) and small-artery occlusion (SAO) (20.0%). Despite adhering to secondary prevention strategies, high sensitivity C-reactive protein, interleukin-6 (IL-6) levels, and impaired renal function were independent risk factors for the residual recurrence risk of LAA subtype, while IL-6 and trimethylamine N-oxide significantly contributed to the residual risk of SAO subtype. Conclusions: LAA and SAO subtypes own the specific nontraditional risk factors while inflammation is a common risk factor for residual recurrence risk of both.

Current Knowledge on Factor V Leiden Mutation as a Risk Factor for Recurrent Venous Thromboembolism: A Systematic Review and Meta-Analysis.

BackgroundThrombophilia screening is widely done in clinical practice, and it is claimed that the extent of venous thromboembolism (VTE) recurrence risk in patients with common defects is still not fully understood.AimWe aimed to summarize data of all observational studies prospectively assessing the association of heterozygous factor V Leiden (FVL) mutation and recurrent VTE in patients with VTE, and to calculate pooled relative risks (RR), overall and in various subgroups.MethodsWe searched MEDLINE and EMBASE databases for cohort studies prospectively assessing VTE recurrence in patients with and without FVL mutation (PROSPERO: CRD42021182800). Data were extracted on cohort and study-level. The methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). RR were calculated overall and in subgroups using a random-effects model.ResultsFrom 31 cohorts, 24 studies were finally included summarizing 13,571 patients. Heterozygous FVL mutation was identified in 2,840 individuals (21%). The methodological quality was estimated to be high in 20 studies (83%). The overall RR was 1.46 (95% CI: 1.31, 1.64), consistent across subgroups.ConclusionsPooling all high-quality epidemiological data, the risk of recurrent VTE was increased by 46% in patients with heterozygous FVL mutation. Against the background of established risk factors, the FVL mutation plays only a marginal role in the risk assessment for recurrent VTE.

Assessment of cell-free DNA (cfDNA) concentrations in the perioperative period can predict risk of recurrence in patients with non-metastatic breast cancer

BackgroundCirculating cell-free DNA (cfDNA) is a potential non-invasive biomarker of disease status in patients with cancer, and provides important diagnostic and prognostic information in breast cancer. The goal of this study was to quantify cfDNA concentrations during the perioperative period and investigate its potential utility to detect recurrence outcomes in patients with breast cancer. MethodsSixty-two (n = 62) patients with non-metastatic breast cancer, undergoing curative-intent surgery were screened for inclusion. Blood samples were collected from these patients: pre-operatively (Preop) and post-operatively (PO) at either of the following PO time points; PO week 1-2, PO week 3-4 and PO weeks 5-12 following surgery. cfDNA was extracted and quantified using nanodrop spectrophotometer. ResultsIn a cohort of 62 patients (age, median (IQR), 51.5(45.0-65.0) years), with a median follow-up of 90 months (interquartile range (IQR),60-120 months), significant association was observed between cfDNA concentrations and risk of recurrence in patients with breast cancer. The group of patients who had disease recurrence during follow-up had significantly higher cfDNA concentrations (cutoff:400 ng/ml) compared to the group of patients who remain disease-free (Preop and PO period: p < 0.0001). The median Recurrence Free Survival (RFS) between the Disease Recurrence (DR) and the Disease Free (DF) groups of patients with breast cancer were 12(20-28.5) months and 72.00 (96-120) months; p < 0.0001). Univariate and multivariate cox regression analysis indicated that postoperative cfDNA concentration (Hazard ratio:5.0, 95% Confidence Interval:1.19-21.28, p = 0.028) was an independent negative prognostic factor for RFS in patients with non-metastatic breast cancer. ConclusionOur study demonstrated that high postoperative cfDNA is associated with increased risk of future recurrence in patients with non-metastatic breast cancer. Further, prospective studies are warranted to validate its clinical utility in breast cancer.

Residual CIS after neoadjuvant chemotherapy and radical cystectomy for muscle invasive bladder cancer: Implications for neoadjuvant trials.

To better define surrogate endpoints for neoadjuvant chemotherapy (NAC) trials in patients with muscle-invasive bladder cancer. We compared survival in patients with carcinoma in-situ (CIS) only vs. complete response following NAC and radical cystectomy (RC). Patients with cT2-4N0M0 disease treated with NAC and RC between 2001 and 2018 were stratified by response: complete response (CR, pT0N0), partial response (PR, pTaN0, pT1N0+/-CIS), CIS-only (pTisN0), stable disease (SD, pT2N0), or progressive disease (PD, >pT2N0). Primary endpoints were overall survival (OS) and risk of recurrence in patients with CIS-only vs. CR. Multivariable Cox proportional hazards regression model was used for OS and a competing risks proportional hazards model was used for risk of recurrence. Of 1,406 patients in our institution cohort, 340 patients met inclusion criteria. Kaplan-Meier mean estimates of OS for CR and CIS-only were 108.9 months (95% CI 89.7-127.9) and 125.8 months (95% CI 112.3-139.3), respectively (P = 0.13). Cox proportional hazards model found no difference in OS between patients with PR (HR 1.06, 95% CI 0.33-2.58, P = 0.897) or CIS-only (HR 0.422, 95% CI 0.15-1.18, P = 0.101) when compared to CR. The risk of recurrence was similar between patients with CIS-only (HR 0.73, 95% 0.29-1.84, P = 0.49) and PR (HR 1.32, 95% CI 0.54-3.29, P = 0.54) when compared to CR on competing risks analysis. Residual CIS-only after NAC and RC demonstrated similar survival outcomes when compared to patients with pathologic CR. Further study in large multi-institutional cohorts may further validate CIS-only as an additional surrogate endpoint after NAC and may inform future trials.

Which Has a Greater Impact on the Recurrence in Young Breast Cancer Patients: Recent Childbirth or Recent Breastfeeding?

Purpose This study explored the effects of recent childbirth and recent breastfeeding on the risk of recurrence in patients with postpartum breast cancer (PPBC). Materials and Methods A bidirectional cohort study was conducted in the First Affiliated Hospital of Nanjing Medical University. 1013 young female breast cancer patients between May 2003 and October 2019 were enrolled. Breast cancer cases were grouped according to the time between giving birth or weaning and diagnosis. The end point of the analysis was disease-free survival (DFS). Results Breast cancer patients diagnosed within 2 years after parturition showed more tumor characteristics that represented poor prognosis and remained at an increased risk for recurrence, even after adjusting for confounding factors (HR = 1.83, p=0.035). When the analysis was limited to patients with ER positive or histological grades I and II, they had a higher risk of recurrence. When weaning was used as the grouping node, patients diagnosed within 2 years after weaning did not show a higher risk of recurrence after adjustment, even when analysis was nearly limited to ER-positive patients. Conclusion Recent reproductive history is an independent prognostic factor and seems to have a stronger impact on breast cancer with lower malignancy. In addition, the effect of recent childbirth on the recurrence of young breast cancer is significantly stronger than that of recent breastfeeding.

Utility of hereditary thrombophilia testing among patients with lower extremity deep vein thrombosis

ObjectiveDespite a growing consensus that testing for hereditary thrombophilia (HT) is not recommended in the setting of venous thromboembolism (VTE), such testing is still often requested. We evaluated the effects of HT on the risk of recurrent VTE for patients with lower extremity deep vein thrombosis (DVT). MethodsWe conducted a multihospital retrospective study of 867 patients with first-time proximal lower extremity DVT who had undergone testing for HT. Patients with and without HT were compared regarding their VTE recurrence risk via Kaplan-Meier and multivariable analysis. ResultsHT was present in 166 patients (19%). The baseline characteristics were similar between the patients with HT and without HT. No significant difference was found in the recurrence rates between the two groups (HT, 17%; no HT, 15%; P = .345). A Kaplan-Meier survival analysis revealed no significant differences in VTE-free survival between the patients with and without HT (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.77-1.84; P = .421). On multivariable analysis, the presence of HT was not associated with recurrent VTE. A higher body mass index (HR, 1.06; 95% CI, 1.03-1.10; P = .004) and unprovoked DVT (HR, 2.48; 95% CI, 1.69-3.66; P < .001) were risk factors for recurrence. ConclusionsHT had no significant impact on the recurrence risk for patients with first-time lower extremity DVT. HT test results would, thus, not be expected to change clinical management and should therefore not be requested routinely for patients with DVT.

Histologic tumor necrosis rate as a predictor of recurrence after surgical treatment for localized clear cell renal cell carcinoma.

Coagulative tumor necrosis (TN) is a potential negative prognostic marker in clear cell renal cell carcinoma (ccRCC). Our study assessed the significance of the TN rate in histological specimens in terms of the risk of recurrence in patients after surgical treatment for localized disease. Our study included 149 subjects surgically treated for ccRCC from 2011 to 2014. Mean postoperative follow-up was 538 days. Presence of TN was assessed by a physician - pathologist in histological specimens. The following findings were described: without necrosis (79 samples), TN rate below 50% (46 samples) and TN rate higher or equal to 50% of the specimen (24 samples). The Kaplan-Meier method, log-rank test and Cox regression analysis were used to evaluate the disease-free survival (DFS). Seventeen patients experienced recurrence - with no TN detected in 3, TN rate below 50% in 6 and TN rate above 50% in 8 patients. There was a significant difference in DSF in patients with proven TN compared to patients without TN (HR 3.83; CI95% 1.489.94%; p=0.006; in multivariate analysis: p=0.031). Evaluation according to the proportion of TN showed a significant difference in DFS in patients with the TN rate below or equal to 50% compared to patients without TN (HR 16.27; CI95% 4.0066.15; p=0.0001; in multivariate analysis: p=0.041). The difference of DSF between patients without TN and with the TN rate higher than 50%, and patients with the TN rate below 50% and higher than 50% was not statistically significant. Our study confirmed TN as a risk factor of disease recurrence. Additionally, a higher TN rate is associated with a significantly higher risk of recurrence.

Combination of epidermal growth factor receptor mutation and the presence of high-grade patterns is associated with recurrence in resected stage I lung adenocarcinoma.

OBJECTIVESThis study aimed to evaluate the prognostic impact of the combination of epidermal growth factor receptor (EGFR) mutation and the presence of high-grade patterns (solid or micropapillary component) in resected stage I lung adenocarcinoma.METHODSPatients who underwent curative resection for pathological stage I lung adenocarcinoma and EGFR mutation analysis were included in this study. The impact of the combination of EGFR mutation and the presence of >5% high-grade patterns on recurrence-free survival (RFS) was retrospectively analysed using Cox proportional hazards model and propensity score-matched analysis.RESULTSAmong the included 721 patients, EGFR mutations were positive in 380 (52.7%). In the EGFR-mutated group, cases with high-grade patterns showed poorer RFS than those without (5-year RFS, 77.7% vs 92.5%, P < 0.001), whereas there were no significant prognostic differences in the EGFR wild-type group (5-year RFS, 89.8% vs 88.2%, P = 0.807). Multivariable analyses revealed that the combination of EGFR mutations and the presence of high-grade patterns was associated with poor RFS (hazard ratio = 1.655, P = 0.035). Furthermore, EGFR mutation was associated with poor RFS in the group with high-grade patterns (hazard ratio = 2.108, P = 0.008). After propensity score matching, EGFR-mutated cases with high-grade patterns showed poorer RFS (P = 0.028).CONCLUSIONSThe combination of EGFR mutation and the presence of high-grade patterns was associated with recurrence in resected stage I lung adenocarcinoma. Histological subtypes, including minor components, should be considered when evaluating the risk of recurrence in patients with EGFR-mutated lung adenocarcinoma.

Three-Dimensional Radiomics Features of Magnetic Resonance T2-Weighted Imaging Combined With Clinical Characteristics to Predict the Recurrence of Acute Pancreatitis.

ObjectiveTo explore the diagnostic value of radiomics model based on magnetic resonance T2-weighted imaging for predicting the recurrence of acute pancreatitis.MethodsWe retrospectively collected 190 patients with acute pancreatitis (AP), including 122 patients with initial acute pancreatitis (IAP) and 68 patients with recurrent acute pancreatitis (RAP). At the same time, the clinical characteristics of the two groups were collected. They were randomly divided into training group and validation group in the ratio of 7:3. One hundred thirty-four cases in the training group, including 86 cases of IAP and 48 cases of RAP. There were 56 cases in the validation group, including 36 cases of IAP and 20 cases of RAP. Least absolute shrinkage and selection operator (LASSO) were used for feature screening. Logistic regression was used to establish the radiomics model, clinical model and combined model for predicting AP recurrence. The predictive ability of the three models was evaluated by the area under the curve (AUC). The recurrence risk in patients with AP was assessed using the nomogram.ResultsThe AUCs of radiomics model in training group and validation group were 0.804 and 0.788, respectively. The AUCs of the combined model in the training group and the validation group were 0.833 and 0.799, respectively. The AUCs of the clinical model in training group and validation group were 0.677 and 0.572, respectively. The sensitivities of the radiomics model, combined model, and clinical model were 0.646, 0.691, and 0.765, respectively. The specificities of the radiomics model, combined model, and clinical model were 0.791, 0.828, and 0.590, respectively. There was no significant difference in AUC between the radiomics model and the combined model for predicting RAP (p = 0.067). The AUCs of the radiomics model and combined model were greater than those of the clinical model (p = 0.008 and p = 0.007, respectively).ConclusionsRadiomics features based on magnetic resonance T2WI could be used as biomarkers to predict the recurrence of AP, and radiomics model and combined model can provide new directions for predicting recurrence of acute pancreatitis.

Tumor cell intrinsic and extrinsic features predictprognosis in estrogen receptor positive breast cancer.

Although estrogen-receptor-positive (ER+) breast cancer is generally associated with favorable prognosis, clinical outcome varies substantially among patients. Genomic assays have been developed and applied to predict patient prognosis for personalized treatment. We hypothesize that the recurrence risk of ER+ breast cancer patients is determined by both genomic mutations intrinsic to tumor cells and extrinsic immunological features in the tumor microenvironment. Based on the Cancer Genome Atlas (TCGA) breast cancer data, we identified the 72 most common genomic aberrations (including gene mutations and indels) in ER+ breast cancer and defined sample-specific scores that systematically characterized the deregulated pathways intrinsic to tumor cells. To further consider tumor cell extrinsic features, we calculated immune infiltration scores for six major immune cell types. Many individual intrinsic features are predictive of patient prognosis in ER+ breast cancer, and some of them achieved comparable accuracy with the Oncotype DX assay. In addition, statistical learning models that integrated these features predicts the recurrence risk of patients with significantly better performance than the Oncotype DX assay (our optimized random forest model AUC = 0.841, Oncotype DX model AUC = 0.792, p = 0.04). As a proof-of-concept, our study indicates the great potential of genomic and immunological features in prognostic prediction for improving breast cancer precision medicine. The framework introduced in this work can be readily applied to other cancers.

Abstract P2-11-19: Estimating the long-term risk of recurrence in patients receiving HER2-targeted agents in HER2+ early-stage breast cancer (ESBC)

Abstract Background: The APHINITY, KATHERINE and ExteNET pivotal trials demonstrated the benefits of HER2-targeted agents for disease-free survival in HER2+ ESBC. However, heterogeneity in patient populations and study designs make assessment of treatment benefits challenging. The objective of this study was to project absolute treatment benefits over a standardized 10-year time horizon. Methods: An epidemiologic model was developed to simulate numbers of distant recurrences for 1000 patients with newly diagnosed HER2+ ESBC in the ExteNET, APHINITY and KATHERINE patient populations and select subgroups. ExteNET evaluated neratinib vs. placebo from 2009 to 2012. APHINITY evaluated pertuzumab + trastuzumab vs. placebo + trastuzumab + standard adjuvant chemotherapy in high-risk patients without neoadjuvant therapy treated from 2011 to 2014. KATHERINE evaluated ado-trastuzumab emtansine (T-DM1) vs. trastuzumab in patients without pathologic complete response (pCR) following neoadjuvant therapy treated from 2013 to 2016. We used disease-free survival curves from each trial as model inputs to estimate the risk of distant recurrence and extrapolated these results to a standardized 10-year follow-up period. We assumed there were no further treatment benefits to prevention of recurrence beyond the follow-up period of the trial. Survival curve trends beyond each trial’s observation period were informed by the trastuzumab arm of the long-term HERA trial follow-up data. Model outputs were distant recurrences for the control arms for each study and the number of distant recurrences avoided from treatment. Results: Over a 10-year time horizon, treatment benefits ranged from 11 to 65 distant recurrences avoided. Treatment benefit differed according to baseline risk of the trial population and treatment effect, with higher-risk populations and greater treatment effect (e.g. KATHERINE trial) tending to yield greater absolute treatment benefit, with the exception of the ExteNET ITT population as changes in the treatment effect over time (non-proportional hazards) made modeling long-term results more complex. Absolute treatment benefits were similar for the intent-to-treat (ITT) group in the KATHERINE trial and the no pCR group in the ExteNET trial; and the ITT groups in the APHINITY and ExteNET trials. Refinement of model projections and inclusion of local recurrences in a more complex modeling structure are ongoing. Conclusions: Results of our simulation suggest that patients with HER2+ ESBC experience a range of reductions in distant recurrence from HER2-targeted agents, depending on baseline risk (pCR and hormone receptor status), and treatment effect. Epidemiologic modeling may be a useful method to estimate long-term outcomes and facilitate evaluation across disparate clinical trials. Table. Modeled benefits of HER2-targeted agents in a cohort of 1000 patients with HER2+ ESBC over a standardized 10-year timeframeSource data inputsModeled outputs (n=1000)Distant recurrences at 10 yearsClinical study characteristicsHazard ratio for distant recurrence from study1Baseline risk: Events in control armTreatment effect: Distant recurrences avoided from treatmentExteNET study (ITT)0.78 (0.60-1.01) at 5 years14318APHINITY study (ITT)0.76 (0.62-0.95) at 6 years10320ExteNET study (HR+; treated within 12 months of trastuzumab receipt)0.57 (0.39-0.83) at 5 years14727APHINITY study (HR+)0.78 (0.51-1.18) at 6 years26111KATHERINE study (no pCR, ITT)0.60 (0.45-0.79) at 3 years26464KATHERINE study (no pCR, HR+)0.57 (0.42-0.75) at 3 years223941ExteNET study (no pCR, HR+; treated within 12 months of trastuzumab receipt)0.61 (0.32-1.11) at 5 years265651Values in parentheses represent 95% confidence intervals. 2Hazard ratio not reported in clinical study publication. Estimated based on reported IDFS hazard ratio and proportion of distant to all invasive recurrences in ITT population. HR = hormone receptor; ITT = intent-to-treat; pCR = pathologic complete response. Citation Format: David L Veenstra, Nathaniel Hendrix, Chantal M Dolan, Kathryn A Fisher, Deepa Lalla, Nina Oestreicher, Adam Brufsky. Estimating the long-term risk of recurrence in patients receiving HER2-targeted agents in HER2+ early-stage breast cancer (ESBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-19.

Abstract P1-13-06: The influence of the oncotype DX breast recurrence score on persistence to endocrine therapy in patients with low-risk ER/PR+ invasive breast cancer

Abstract Intro: The Oncotype DX breast recurrence score provides newly diagnosed patients with low-risk ER/PR+ invasive breast cancer with an estimation of their 10-year risk of distant recurrence if compliant with five years of endocrine therapy. Despite the well-established benefits of endocrine therapy, to include a decrease in local and distant disease recurrence, many patients will discontinue endocrine therapy prior to five years, defined as non-persistence. We hypothesized that the individual perception of risk of recurrence conveyed by the Oncotype DX breast recurrence score directly influences persistence with endocrine therapy and patients with higher Oncotype DX breast recurrence scores may have higher rates of persistence when compared to a similar cohort with lower recurrence scores. Further, we hypothesized that disease recurrence in women with low-risk (defined as less than 26) ER/PR+ breast cancer is due primarily to non-persistence with endocrine therapy. Methods: Our study included 198 patients with low-risk ER/PR+ breast cancer treated at a comprehensive cancer center between April 2011 and April 2014 with sufficient-follow-up data of at least 5 years. Persistence was determined by chart review and defined as a minimum duration of 55 months on endocrine therapy. Multivariable ANOVA and Fisher Chi Square Exact test were used to compare the recurrence score, 10-year risk of distant recurrence, and rates of recurrence between persistent vs non-persistent patients. Results: The average recurrence score of our cohort was 14.74 with an average 10-year risk of distant recurrence of 9.8 percent with five years of endocrine therapy. The average recurrence score was 15.24 in the persistent group vs. 13.18 for the non-persistent group (p=0.029). The average 10-year risk of distance recurrence was 10.1% in persistent patients vs 9% in non-persistent patients (p=0.019). The recurrence rate (both local and distant) was 4% in persistent patients vs 16% in non-persistent patients at 5- year follow (P=&amp;lt;0.01). Discussion: Non-persistence to endocrine therapy represents a major unmet need in breast cancer care. The Oncotype DX breast recurrence score significantly influences persistence to endocrine therapy as our retrospective review demonstrated that patients with low-risk ER/PR+ locally invasive breast cancer with higher Oncotype DX scores are more likely to complete the recommended 5-years of endocrine therapy. Further, despite having a lower average Oncotype DX score overall, the non-persistent group had a higher rate of recurrence when compared to the persistent group. This finding further substantiates the overall effectiveness of endocrine therapy in reducing the risk of future recurrence in patients with low-risk ER/PR+ breast cancer. Mindful framing of Oncotype DX test results by providers represents a potential avenue to increase persistence through the modulation of individual risk perception and may ultimately lead to decreased rates of disease recurrence in patients with low-risk ER/PR+ invasive breast cancer. Citation Format: Jonathan Pirruccello, Elaine Kuhn, Mary Chamberlin. The influence of the oncotype DX breast recurrence score on persistence to endocrine therapy in patients with low-risk ER/PR+ invasive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-13-06.

Abstract P2-13-14: Pattern of recurrence after pathologic complete response after neoadjuvant chemotherapy in patients with early HER2-positive breast cancer: Real-world evidence

Abstract Background The real-world risk of disease recurrence in patients with HER2-positive early breast cancer who achieved pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) and/or HER2-targeted therapy is unclear. This study aims to identify the patterns and risk factors of disease recurrence after NAC in patients with HER2-positive early breast cancer who achieved a pCR or not. Methods 930 HER2 positive early breast cancer patients who received NAC were identified in the Severance Breast Cancer Registry at the Yonsei Cancer Center and Gangnam Severance Hospital in Seoul, Republic of Korea, between 2006 and 2020. NAC included 3 regimens: only chemotherapy. (CTx), chemotherapy plus trastuzumab (CTx+H), and chemotherapy plus dual anti-HER2 therapy (TCHP). The pCR was defined as the absence of residual invasive cancer in the resected breast specimen and the axillary lymph nodes (ypT0/TisN0) after neoadjuvant systemic therapy. Recurrence of disease was defined as recurrence of ipsilateral locoregional invasive breast cancer, distant disease recurrence, or death. Results The median follow-up duration was 42.0 months (range 4-171), and median age was 51 years old (range 22-80). The rate of pCR was 52.2% (485/930). Depending on the achieved a pCR, the loco-regional recurrence rate was 4.0% (18/445) vs 1.0% (5/485), and the distant recurrence rate was 11.0% (49/445) vs 3.9% (19/445). Of the 79 patients who relapsed, 30.4% (n=24) had achieved a pCR and 69.6% (n=55) had residual disease. The 4-year recurrence risk was 6.9% for patients who achieved pCR versus 12.8% for those who did not (p&amp;lt;0.001). Of the 24 patients who achieved pCR who relapse, 22 (91.7%) occurred within 4 years of diagnosis. Of the 55 patients who did not achieve a pCR who relapse, 48 (87.3%) occurred within 4 years of diagnosis. Among the 19 patients who developed distant recurrence who attained a PCR, the most common first recurrent sites were lung (42.1%), brain (36.8%), and distant lymph nodes (36.1%). Lung and brain metastases occurred in 87.5% and 85.7% within 3years of diagnosis. If pCR was reached, the NAC regimen or HR status did not affect the recurrence-free survival. However, clinical stages II and III at diagnosis (HR (hazard ratio) =35.3 and HR=114.5, p=0.037) were independent predictor of inferior recurrence-free survival in the pCR group. Conclusion Overall, patients who attained a pCR have a better outcome compared to those with residual disease, regardless of hormone status or type of NAC regimen. However, despite achieving pCR after NAC, patients with HER2-positive, clinical stage II/III remain at risk for disease recurrence within 4 years of diagnosis. Citation Format: Jee Hung Kim, Jii Bum Lee, Soong Joon Bae, Sung Gwe Ahn, Joon Jeong, Min Hwan Kim, Seul-Gi Kim, Gun Min Kim, Jee Ye Kim, Hyung Seok Park, Seho Park, Byeong Woo Park, Seung Il Kim, Joohyuk Sohn. Pattern of recurrence after pathologic complete response after neoadjuvant chemotherapy in patients with early HER2-positive breast cancer: Real-world evidence [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-14.

Expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study

Objective National Comprehensive Cancer Network (NCCN) guidelines for cutaneous melanoma (CM) recommend physicians consider increased surveillance for patients who typically have lower melanoma survival rates (stages IIB-IV as determined by the American Joint Committee on Cancer (AJCC), 8th edition). However, up to 15% of patients identified as having a low recurrence risk (stages I-IIA) experience disease recurrence, and some patients identified as having a high recurrence risk will not experience any recurrence. The 31-gene expression profile test (31-GEP) stratifies patient recurrence risk into low (Class 1) and high (Class 2) and has demonstrated risk-appropriate impact on disease management and clinical decisions. Methods Five-year plans for lab work, frequency of clinical visits, and imaging pre- and post-31-GEP test results were assessed for a cohort of 509 stage I-III patients following an interim subset analysis of 247 patients. Results After receiving 31-GEP results, 50.6% of patients had a change in management plans in at least one of the following categories—clinical visits, lab work, or surveillance imaging. The changes aligned with the risk predicted by the 31-GEP for 76.1% of patients with a Class 1 result and 78.7% of patients with a Class 2 result. A Class 1 31-GEP result was associated with changes toward low-intensity management recommendations, while a Class 2 result was associated with changes toward high-intensity management recommendations. Conclusion The 31-GEP can stratify patient recurrence risk in patients with CM, and clinicians understand and apply the prognostic ability of the 31-GEP test to alter patient management in risk-appropriate directions.