Low-risk Cohort Research Articles

Subcutaneous Fat Abundance and Density Are Associated with an Enhanced Response to Immunotherapy in Metastatic Melanoma: A Retrospective Cohort Study

Despite the impressive efficacy of immune checkpoint inhibitors (ICIs) in the treatment of metastatic melanoma, not all patients respond to therapy. In addition, ICI harbors the risk for serious adverse events (AEs), highlighting the need for novel biomarkers predicting treatment response and occurrence of AEs. Recently, the identification of enhanced response to ICI in obese patients has indicated that body composition might influence treatment efficacy. The aim of the current study is to assess radiologic measurements of body composition as biomarkers for treatment response and AEs to ICI in melanoma. In the current work, we analyze adipose tissue abundance and density, as well as muscle mass via computed tomography scans in a retrospective cohort of 100 patients with non-resectable stage III/IV melanoma receiving first-line treatment with ICI in our department. From these, we investigate the impact of the subcutaneous adipose tissue gauge index (SATGI) and other parameters of body composition on treatment efficacy and occurrence of AEs. Low SATGI was associated with prolonged progression-free survival (PFS) in univariate and multivariate analyses (hazard ratio 2.56 [95% CI 1.18-5.55], P = .02), as well as an enhanced objective response rate (50.0% vs 27.1%; P = .02). Further analysis with a random forest survival model highlighted a nonlinear relationship between SATGI and PFS with a clear separation into high- and low-risk cohorts separated by the median. Finally, a significant enrichment of cases with vitiligo, but no other AEs, was observed in the SATGI-low cohort (11.5% vs 0%; P=.03). We identify SATGI as a biomarker predicting treatment response to ICI without increased risk for severe AEs in melanoma.

#3068 POTASSIUM LEVELS AND EGFR DO NOT PREDICT SEVERE HYPERKALEMIA FOLLOWING SPIRONOLACTONE INTRODUCTION IN PATIENTS WITH CKD AT HIGH RISK OF HYPERKALEMIA

Abstract Background and Aims Mineralocorticoid receptor antagonists (MRA) reduce blood pressure, albuminuria and the rate of disease progression in patients with chronic kidney disease (CKD) and albuminuria. Despite these apparent benefits, only a very small fraction of patients with CKD are treated with an MRA. This may in part be due to the fear of hyperkalemia (HK), which in the most severe cases can cause life-threatening arrythmias. Indeed, international guidelines and previous studies have excluded patients believed to be at high risk of severe HK from treatment with MRA including patients with pre-existing high serum potassium. To examine if the risk of HK can in fact be predicted by baseline potassium levels or eGFR, we performed a clinical study testing the effect of introducing spironolactone on plasma potassium (P-K) levels in closely monitored, high-risk patients excluded from other studies. Secondly, we analyzed the effect of spironolactone on eGFR and albuminuria. Method We included patients with eGFR 25-60 ml/min/1.73 m2 on maximal tolerated RAAS-blockade (ACEi or ARB) and a history of at least two HK-episodes (P-K > 4.5mmol/l) within 24 months prior to inclusion. Following dietary counselling on avoidance of potassium-rich foods, spironolactone was initiated at 25 mg daily. If tolerated as defined by a decline in eGFR < 30%, a P-K ≤ 5.5mmol/l and the absence of severe hypotension, the dose was increased to 50 mg after two weeks. Total follow-up was four weeks measuring P-K, eGFR, blood pressure and spot urine albumin creatinine ratio. Results from maximal tolerated dose were compared to baseline using paired t-test. In a post-hoc analysis, patients were grouped based on the occurrence of severe HK (P-K > 5.5mmol/l) or not, and baseline characteristics and the change from baseline to maximal dose were compared using unpaired t-test. Linear regression model was used to test the association between baseline P-K vs. P-K at maximal dose of spironolactone and the change in P-K from baseline to maximal dose of spironolactone vs. baseline eGFR. Results Fifty-eight patients were included with a mean age of 65 years. Forty-seven were males and 23 had diabetes. Forty-eight patients reached a spironolactone dose of 50 mg. Following spironolactone introduction, mean eGFR declined from 39 at baseline to 34ml/min/1.73 m2 (p<0.001) and albuminuria was reduced from a median of 1276mg/g to 654 mg/g (49%; 95%CI: 44 – 54%) with no significant change in blood pressure. Mean P-K increased 0.5mmol/l (95% CI 0.3 - 0.7mmol/l) from 4.7mmol/l to 5.2mmol/l. Seventeen patients developed severe HK with a P-K > 5.5mmol/l and four were briefly admitted with a P-K > 6.2mmol/l. Importantly, there was no difference in baseline P-K nor eGFR in patients that developed severe HK when compared with those that did not (4.70 vs 4.67 mmol/L, p = 0.83 and 36.2 vs. 40.1 ml/min/1.73 m2, p = 0,13). Furthermore, baseline P-K did not correlate with P-K at maximum spironolactone dose (Figure 1) and the change in P-K did not significantly correlate with baseline eGFR (Figure 2). Conclusion Short-term treatment with spironolactone in patients with CKD at high risk of HK leads to similar reductions in albuminuria and eGFR when compared with low-risk cohorts. With dietary counseling, 30% of patients will develop severe HK within 4 weeks. Importantly and contrary to common belief, neither baseline P-K levels nor baseline eGFR were associated with the development of severe HK. Thus, excluding patients from MRA treatment based solely on eGFR and P-K levels is not appropriate. Instead, we believe an empirical approach based on dietary counseling and close monitoring of P-K should be used.

The impact of postoperative complications on oncological outcomes of liver transplantation for hepatocellular carcinoma: A competing risk analysis

ObjectiveTo investigate the influence of postoperative complications on tumor-related (TRD), disease-free survival (DFS) and overall survival (OS) in patients undergoing liver transplant (LT) for hepatocellular carcinoma (HCC). MethodsWe retrospectively evaluated 425 LTs for HCC from 2010 to 2019. Postoperative complications were classified according to Comprehensive Complication Index (CCI) and the posttransplant risk of TRD assessed through Metroticket 2.0 calculator. The population was stratified into high-risk and low-risk cohorts based on the predicted TRD risk of 80%. In a second step, we re-evaluated TRD, DFS and OS of both cohorts according to a further stratification based on 47.3 points of CCI cut-off. ResultsIn the low-risk cohort, we observed a significantly better DFS (84% vs. 46%, p<0.001), TRD (3% vs. 26%, p<0.001) and OS (89% vs. 62%, p<0.001) in the group with CCI < 47.3. In the high-risk cohort, patients with CCI < 47.3 had significantly better DFS (50% vs. 23%, p = 0.003) and OS (68% vs. 42%, p = 0.02) and a comparable TRD (22% vs. 31%, p = 0.142). ConclusionsA complicated postoperative course negatively influenced long-term survival. This poorer oncological outcome associated with in-hospital postoperative complications suggests that every effort should be made to improve the early posttransplant course in HCC patients, including a careful donor-to recipient match and use of new perfusion technologies.

Scientific Review of the Knowledge Gap in the Efficacy of Antiviral Therapy to a Low-Risk Kidney Transplant Population Cohort

Scientific Review of the Knowledge Gap in the Efficacy of Antiviral Therapy to a Low-Risk Kidney Transplant Population Cohort

Response-adapted therapy (tx) with nivolumab plus brentuximab vedotin (nivo + BV) without autologous hematopoietic cell transplantation (auto-HCT) in children, adolescents, and young adults (CAYA) with low-risk relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL): CheckMate 744.

7515 Background: Outcomes are poor for patients (pts) with cHL who develop R/R disease after first-line (1L) chemotherapy ± radiotherapy (RT). Salvage tx that attain high event-free survival (EFS) rates and minimize late toxicity by omitting high-dose chemotherapy (HDCT)/auto-HCT are needed. CheckMate 744 (NCT02927769) is the first multicenter phase 2 study evaluating a risk-stratified, response-adapted salvage tx with nivo + BV in CAYA with R/R cHL. In the standard-risk cohort, complete molecular response (CMR) rate before consolidation with HDCT/auto-HCT was 94% (Harker-Murray et al. Blood 2022). With highly active salvage tx, pts in low-risk cohort could achieve high EFS without HDCT/auto-HCT; we report data from this cohort. Methods: Pts were aged 5–30 y and had ≤ 3 cycles (C) of 1L anthracycline-based systemic tx. Risk stratification was described in Harker-Murray et al. Pts received 4C of nivo + BV induction. Pts with CMR received additional 2C nivo + BV before involved-site radiation therapy (ISRT) consolidation (dose, 30–30.6 Gy). Pts with suboptimal response received 2C BV + bendamustine intensification; pts with CMR proceeded to ISRT consolidation. Primary endpoints: CMR rate (Lugano 2014) any time before ISRT and 3-y EFS rate, both per blinded independent central review (BICR). For CMR and overall response rate (ORR), a 90% confidence interval (CI) was used per statistical plan. Results: Among 28 pts treated with nivo + BV, median (range) age was 17 (6–27) y; 64% of pts were aged &lt; 18 y. Most (64%) pts had stage II disease at relapse; 82% had relapse ≥ 12 mo after 1L tx, 2 pts had prior RT. Median (range) follow-up was 31.9 (2.2–55.3) mo. CMR, ORR, 3-y EFS and PFS rates are shown in Table. Median duration of response was not reached; 87% of pts had sustained response at 36 mo’ follow-up. Efficacy outcomes were comparable in the pediatric population (CMR per BICR before ISRT, 88.9%; 3-y EFS rate, 78.3%). During induction, 22 (78.6%) pts had treatment-related adverse events (TRAEs; grade 3/4, 25.0% pts; hematologic, &lt; 10% pts; immune-mediated, 21.4%). Serious AEs leading to discontinuation included rash, pyrexia, and acute kidney injury (1 pt each). Conclusions: The findings demonstrate that most CAYA with low-risk R/R cHL can be salvaged with chemoimmunotherapy with a favorable toxicity profile, and do not require HDCT/auto-HCT. Clinical trial information: NCT02927769 . [Table: see text]

Combined associations of a healthy lifestyle and body mass index on colorectal cancer recurrence and survival: A cohort study.

3609 Background: Colorectal cancer (CRC) risk is associated with modifiable lifestyle factors including smoking, physical inactivity, Western diet, and excess body weight. The impact of lifestyle factors on survival is less known. A cohort study was conducted to investigate the combined effects of a pre-diagnostic healthy lifestyle and body mass index (BMI) on prognosis following CRC diagnosis. Methods: Treatment and follow-up data were collected from the patient files of 1098 participants from the Swedish Colorectal cancer low-risk study cohort including stage I-III CRC patients. A healthy lifestyle and BMI (HL) score was computed using self-reported data on smoking status, physical activity, adherence to a Mediterranean diet pattern, and BMI five years before diagnosis, and divided into four categories ranging from least to most healthy. Survival analyses were performed to assess recurrence-free survival and overall survival across categories of exposure, using the Kaplan-Meier method and Cox proportional hazards model, the latter adjusted for age, sex, and educational level. Results: Among 1098 participants with stage I-III CRC, 233 (21.2%) had an HL score of 0-1 (least healthy), 354 (32.2%) HL score of 2, 357 (32.5%) HL score of 3 and 154 (14.0) HL score of 4 (most healthy). Participants missing follow-up data (n = 29) or relapsing ≤ 6 months (n = 29) were excluded from the recurrence-free survival analysis. 221 events of cancer recurrence were observed among 1040 participants during a median follow-up time of 4.3 years, and 542 deaths among 1098 participants during a median follow-up time of 6.3 years. Patients with the healthiest lifestyle had an improved recurrence-free survival (HL 4 vs HL0-1, HRadj 0.51 (95% CI 0.31-0.83) and overall survival (HL 4 vs HL 0-1, HRadj 0.52 (95% CI 0.38-0.70)). Stratifying these results for cancer stage (I-III) and tumor site (colon/rectum) did not alter estimated HR:s or 95% CI:s. Avoidance of smoking and being physically active were independently associated with improved recurrence-free survival and overall survival: non-smoking vs smoking HRadj 0.62 (95% CI 0.43-0.90), high vs low levels of physical activity HRadj 0.71 (95% CI 0.54-0-94)). Conclusions: Our study indicates that pre-diagnostic adherence to a healthy lifestyle may increase the recurrence-free and overall survival of patients with stage I-III CRC. Avoidance of smoking and being physically active were the strongest risk-reducing factors for these outcomes. [Table: see text]

0470 Factors Associated with Discordant Initial Home Sleep Apnea Testing and Polysomnography

Abstract Introduction Nocturnal polysomnography (PSG) is the gold standard for diagnosing obstructive sleep apnea (OSA). Home sleep apnea tests (HSAT) have been incorporated in the diagnostic algorithm in patients with a high pre-test suspicion of OSA. While many studies have compared HSATs with PSGs, it is not well understood what factors may be responsible for inconclusive HSAT results. Methods We performed a retrospective chart review of adult patients who underwent a non-diagnostic HSAT evaluation, who subsequently tested positive for OSA (on PSG) between 1/1/2022 and 11/1/2022. We collected demographic and sleep study data. Patients who did not have a follow up PSG were excluded. Results A total of 20 patients were reviewed. 80% had a negative HSAT with a positive subsequent PSG. The average age was 33.9 years (SD +/- 11.3 years). 43% were male and 50% were Caucasian. The average BMI was 29 kg/m2 (SD +/- 5.3 kg/m2). The average Epworth Sleepiness Scale score (ESS) was 8 (median 6.5) with only 31% reporting an ESS &amp;gt;10. The average HSAT recording time was 449.1 minutes. The average respiratory disturbance index (RDI) on the follow up PSG was 17.7 events/hour of sleep (SD +/- 12). Only 1 patient was diagnosed with severe OSA. 38% were diagnosed with anxiety in this cohort. Other co-morbidities were insignificant. Of all the HSATs performed, 40% were denied for an initial PSG evaluation and converted to an HSAT evaluation. Conclusion HSATs are validated in patients with a high pretest probability of OSA. Anxiety was found in one third of patients included (possibly contributing to a negative initial HSAT). Patient demographics however were also not remarkable for a high risk of OSA in this group (e.g. non-obese, &amp;lt; 55 years, female). The subsequent diagnosis for OSA was also only mild or moderate (93.8%) in this lower risk cohort. Hence, another explanation for the initial negative HSAT evaluation may have been the insurance denial of the initial PSG request (40%). Denials of low risk patients for PSG may contribute to a misuse of resources. We also need to educate referring physicians to follow appropriate HSAT ordering criteria (based on high OSA risk factors). Support (if any)

Predicting post-discharge venous thromboembolism and bleeding among medical patients: External validation of a novel risk score utilizing ubiquitous biomarkers

BackgroundPost-hospitalization thromboprophylaxis can reduce venous thromboembolism (VTE) risk for non-surgical patients but may carry bleeding risks. We aimed to externally validate the Intermountain Risk Scores for hospital-associated venous thromboembolism (HA-VTE IMRS) and major bleeding (HA-MB IMRS) for VTE and bleeding outcomes. MethodsRetrospective cohort study of adult patients discharged alive from medical services between 2015 and 2019. HA-VTE IMRS and HA-MB IMRS were calculated at the time of hospital discharge and dichotomized as high- or low-risk as described in the derivation manuscript. 90-day post-discharge VTE outcomes were assessed from diagnostic radiology reports, and bleeding outcomes were assessed using ICD-10 codes and blood bank transfusion records. ResultsAmong 113,578 patients in the study, 66,340 patients (58.4 %) had a low-risk HA-VTE IMRS <7, versus 47,238 (41.6 %) high-risk ≥7. For bleed prediction, 71,576 patients (63 %) had a low-risk HA-MB IMRS <8, versus 42,002 (37 %) high-risk ≥8. VTE incidence was 1.1 % and 0.6 % while major bleeding incidence was 1.3 % and 0.1 % in high-risk versus low-risk cohorts, respectively. AUCs for VTE and bleed outcome discrimination were 0.59 and 0.78, respectively. Patients with a combined high-risk VTE score and low-risk bleeding score comprised 14.5 % of the population. ConclusionIn this external validation study, the HA-VTE IMRS had poor discrimination for VTE but the HA-MB IMRS had good discriminatory ability for major bleeding events. A sizable minority of patients were categorized as high VTE risk with low bleed risk, a population which may have an optimal risk-benefit profile for post-hospital thromboprophylaxis.

Mast cell marker gene signature: prognosis and immunotherapy response prediction in lung adenocarcinoma through integrated scRNA-seq and bulk RNA-seq.

Mast cells, comprising a crucial component of the tumor immune milieu, modulate neoplastic progression by secreting an array of pro- and antitumorigenic factors. Numerous extant studies have produced conflicting conclusions regarding the impact of mast cells on the prognosis of patients afflicted with lung adenocarcinoma (LUAD). Employing single-cell RNA sequencing (scRNA-seq) analysis, mast cell-specific marker genes in LUAD were ascertained. Subsequently, a mast cell-related genes (MRGs) signature was devised to stratify LUAD patients into high- and low-risk cohorts based on the median risk value. Further investigations were conducted to assess the influence of distinct risk categories on the tumor microenvironment. The prognostic import and capacity to prognosticate immunotherapy benefits of the MRGs signature were corroborated using four external cohorts. Ultimately, the functional roles of SYAP1 were validated through in vitro experimentation. After scRNA-seq and bulk RNA-seq data analysis, we established a prognostic signature consisting of nine MRGs. This profile effectively distinguished favorable survival outcomes in both the training and validation cohorts. In addition, we identified the low-risk group as a population more effective for immunotherapy. In cellular experiments, we found that silencing SYAP1 significantly reduced the proliferation, invasion and migratory capacity of LUAD cells while increasing apoptosis. Our MRGs signature offers valuable insights into the involvement of mast cells in determining the prognosis of LUAD and may prove instrumental as a navigational aid for immunotherapy selection, as well as a predictor of immunotherapy response in LUAD patients.

Identification of m6A-related lncRNAs as prognostic signature within colon tumor immune microenvironment.

The current study probed prognosis-related potential for m6A-related lncRNAs signatures within colon tumor immune microenvironment (TIM). After downloading transcriptomic datasets for colon cancer (CC) patients from The Cancer Genome Atlas (TCGA), they were divided, in a 1:1 ratio, within training or test datasets. m6A-related lncRNAs were then scrutinized across such dataset using Pearson correlation assessment before generating a m6A-related lncRNAs prognosis-related model using the training dataset. The latter was then validated with the test and the whole dataset. In addition, we compared the differences of TIM and the estimated IC50 of drug response between the high- and low-risk groups. Overall survival (OS) resulted as linked with 11 m6A-related lncRNAs, while within the developed prognosis-related model, areas-under-curves were as follows: within training dataset, values at 3-, 4-, and 5-years were 0.777, 0.819, and 0.805, accordingly, and for test one, they were 0.697, 0.682, and 0.706, respectively. Finally, the values for the whole dataset were 0.675 (3-year), 0.682 (4-years), and 0.679 (5-years), accordingly. Moreover, CC cases categorized within low-risk cohort demonstrated enhanced OS (p < .0001), lower metastasis (p = 2e-06) and lower T stage (p = .0067), more instability for microsatellite status (p = .012), and downregulation for PD-L1, PD-1, CTLA-4, LAG3, and HAVCR2 (p < .05). In addition, risk scorings were significantly linked to the degree of infiltrative intensity for CD8 and CD4 (memory resting) T-cells, T-regulatory (Tregs), and Mast cells triggering (p < .05). Patients with low infiltrative propensity for CD4 T-cells also had better OS (p = .016). Moreover, six representative drugs were found to be sensitive for treating CC patients. A robust m6A-related prognostic model with great performances was developed before exploring the TIM characteristics and its potential therapeutic drugs, which might improve the prognosis and therapeutic efficacy.

Morpho-mechanistic screening criteria for the echocardiographic detection of rheumatic heart disease

IntroductionScreening echocardiography, guided by the current World Heart Federation (WHF) criteria, has important limitations that impede the establishment of large-scale rheumatic heart disease (RHD) control programmes in endemic regions. The...

A nomogram for predicting overall survival of patients with squamous cell carcinoma of the floor of the mouth: a population-based study.

Floor of mouth squamous cell carcinoma (SCCFOM) is a rare but aggressive malignancy with 5-year overall survival (OS) rates below 40% in published studies. However, the clinicopathological predictors of the prognosis of SCCFOM remain undefined. We aimed to establish a model to predict the survival outcomes of SCCFOM. We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with SCCFOM between 2000 and 2017. Data on patient demographics, treatment modalities, and survival outcomes were retrieved. Risk factors for OS were evaluated by survival and Cox regression analyses. A nomogram for OS was developed based on the multivariate model and split the patients into high- and low-risk cohorts based on cutoff values. Overall, 2014 SCCFOM patients were included in this population-based study. Multivariate Cox regression showed that age, married status, grade, American Joint Committee on Cancer stage, radiotherapy, chemotherapy, and surgery were significant risk factors for survival. A nomogram was established using the regression model. The C-indices, areas under the receiver operating characteristic curves, and calibration plots demonstrated the reliable performance of the nomogram. Patients assigned to the high-risk group had a significantly lower survival rate. The nomogram predicting survival outcomes of SCCFOM patients based on clinical information showed good discriminative ability and prognostic accuracy. Our nomogram could be used to predict the survival probabilities for SCCFOM patients at different timepoints.

External validation of the ACC/AHA ASCVD risk score in a Colombian population cohort

No cardiovascular risk score has included Latin American patients in its development. The ACC/AHA ASCVD risk score has not been validated in Latin America; consequently, its predictive capacity in the population of the region is unknown. The aim of this study is to evaluate the discrimination capacity and calibration of the ACC/AHA ASCVD score to predict the 10-year risk of a cardiovascular event in a primary prevention cohort followed in a Colombian hospital. A retrospective cohort study was conducted in primary prevention patients belonging to an intermediate/high-risk and low-risk cohort without established atherosclerotic disease. Cardiovascular risk was calculated at inclusion. The calibration was analyzed by comparing observed and expected events in the different risk categories. A discrimination analysis was made using the area under the ROC curve and C statistic. A total of 918 patients were included—202 from the intermediate/high-risk and 716 from the low-risk cohort. The median cardiovascular risk was 3.6% (IQR 1.7–8.5%). At the 10-year follow-up, 40 events (4,4%) occurred. The area under the ROC curve was 0.782 (95% CI 0.71–0.85). The Hosmer–Lemeshow test did not show differences between expected and observed events. The ACC/AHA ASCVD score is calibrated and has good discrimination capacity in predicting 10-year risk of cardiovascular events in a Colombian population.

Quantitative background parenchymal enhancement and fibro-glandular density at breast MRI: Association with BRCA status.

To investigate whether MRI-based measurements of fibro-glandular tissue volume, breast density (MRBD), and background parenchymal enhancement (BPE) could be used to stratify two cohorts of healthy women: BRCA carriers and women at population risk of breast cancer. Pre-menopausal women aged 40-50years old were scanned at 3T, employing a standard breast protocol including a DCE-MRI (35 and 30 participants in high- and low-risk groups, respectively). The dynamic range of the DCE protocol was characterised and both breasts were masked and segmented with minimal user input to produce measurements of fibro-glandular tissue volume, MRBD, and voxelwise BPE. Statistical tests were performed to determine inter- and intra-user repeatability, evaluate the symmetry between metrics derived from left and right breasts, and investigate MRBD and BPE differences between the high- and low-risk cohorts. Intra- and inter-user reproducibility in estimates of fibro-glandular tissue volume, MRBD, and median BPE estimations were good, with coefficients of variation < 15%. Coefficients of variation between left and right breasts were also low (< 25%). There were no significant correlations between fibro-glandular tissue volume, MRBD, and BPE for either risk group. However, the high-risk group had higher BPE kurtosis, although linear regression analysis did not reveal significant associations between BPE kurtosis and breast cancer risk. This study found no significant differences or correlations in fibro-glandular tissue volume, MRBD, or BPE metrics between the two groups of women with different levels of breast cancer risk. However, the results support further investigation into the heterogeneity of parenchymal enhancement. • A semi-automated method enabled quantitative measurements of fibro-glandular tissue volume, breast density, and background parenchymal enhancement with minimal user intervention. • Background parenchymal enhancement was quantified over the entire parenchyma, segmented in pre-contrast images, thus avoiding region selection. • No significant differences and correlations in fibro-glandular tissue volume, breast density, and breast background parenchymal enhancement were found between two cohorts of women at high and low levels of breast cancer risk.

Abstract 5471: Integrating tumor-intrinsic and immunological factors to identify immunogenic breast cancers from a low-risk cohort; results from the randomized SweBCG91RT trial

Abstract Purpose: The local immune infiltrate’s influence on tumor progression may be linked to tumor-intrinsic factors. This study aimed to investigate whether integrating immunological and tumor-intrinsic factors could identify patients who may be candidates for de-escalation of radiotherapy (RT).Experimental Design: The practice-changing SweBCG91RT trial included 1178 patients with stage I-IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT with sparse use of systemic therapy (95% without systemic therapy) and followed for a median time of 15.2 years. We developed two gene expression models to capture immunological activity and immunomodulatory tumor-intrinsic qualities, respectively. We then analyzed if combining these two variables could identify a subgroup where RT de-escalation is feasible. Results: The immunomodulatory model correlated with proliferation and was named Proliferative Index. The immunological model was enriched for T cell signatures and was named Immunescore. Increased Proliferative Index predicted an increased prognostic benefit from Immunescore (pinteraction=0.01). Combining the two models stratified patients who may be recommended an escalated RT (RT boost) by RT benefit and prognosis. Patients with a low predicted risk benefited from standard RT (HR: 0.28, CI 95% 0.09-0.85, p=0.025) and had a 5.4% 10-year incidence of ipsilateral breast tumor recurrence (IBTR) after radiation. In contrast, the group with a high predicted risk, characterized by rapidly proliferating tumors without an immune infiltrate, had a clinically meaningful high 10-year incidence of IBTR despite RT treatment (19.5% (CI 95% 12.2-30.3)). Conclusions: Integrating tumor-intrinsic and immunological factors may identify immunogenic tumors in early-stage breast cancer populations and identify patients for whom de-escalated RT may be appropriate. Patients with rapidly proliferating tumors and an immune infiltrate may be candidates for RT de-escalation. Citation Format: Axel Stenmark Tullberg, Martin Sjöström, Emma Niméus, Fredrik Killander, Laura Chang, Felix Y. Feng, Corey W. Speers, Lori J. Pierce, Anokó Kovács, Dan Lundstedt, Erik Holmberg, Per Karlsson. Integrating tumor-intrinsic and immunological factors to identify immunogenic breast cancers from a low-risk cohort; results from the randomized SweBCG91RT trial. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5471.

Cerebral Embolic Protection Devices: Current State of the Art.

Transcatheter aortic valve replacement (TAVR) has become a first-line treatment for severe aortic stenosis with intermediate to high-risk population with its use increasingly expanding into younger and low-risk cohorts as well. Cerebrovascular events are one of the most serious consequential complications of TAVR, which increase morbidity and mortality. The most probable origin of such neurological events is embolic in nature and the majority occur in the acute phase after TAVR when embolic events are most frequent. Cerebral embolic protection devices have been designed to capture or deflect these emboli, reducing the risk of peri-procedural ischaemic events. They also carry the potential to diminish the burden of new silent ischemic lesions during TAVR. Our review explores different types of these device systems, their rationale, and the established clinical data.

The role of multiparametric magnetic resonance in active surveillance of a low-risk prostate cancer cohort from clinical practice.

Active surveillance (AS) is considered a suitable management practice for those patients with low-risk prostate cancer (PCa). At present, however, the role of multiparametric magnetic resonance imaging (mpMRI) in AS protocols has not yet been clearly established. To determine the role of mpMRI and its ability to detect significant prostate cancer (SigPCa) in PCa patients enrolled in AS protocols. There were 229 patients enrolled in an AS protocol between 2011 and 2020 at Reina Sofía University Hospital. MRI interpretation was based on PIRADS v.1 or v.2/2.1 classification. Demographics, clinical, and analytical data were collected and analyzed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for mpMRI in different scenarios. We defined SigPCa and reclassification/progression as a Gleason score (GS) ≥ 3 + 4, a clinical stage ≥T2b, or an increase in PCa volume. Kaplan-Meier and log-rank tests were used to estimate progression-free survival time. Median age was 69.02 (±7.73) at diagnosis, with a 0.15 (±0.08) PSA density (PSAD). Eighty-six patients were reclassified after confirmatory biopsy, with a suspicious mpMRI an indication for a clear reclassification and risk-predictor factor in disease progression (p < 0.05). During follow-up, 46 patients were changed from AS to active treatment mainly due to disease progression. Ninety patients underwent ≥2mpMRI during follow-up, with a median follow-up of 29 (15-49) months. Thirty-four patients had a baseline suspicious mpMRI (at diagnostic or confirmatory biopsy): 14 patients with a PIRADS 3 and 20 patients with ≥PIRADS 4. From 14 patients with a PIRADS 3 baseline mpMRI, 29% progressed radiologically, with a 50% progression rate versus 10% (1/10 patients) for those with similar or decreased mpMRI risk. Of the 56 patients with a non-suspicious baseline mpMRI (PIRADS < 2), 14 patients (25%) had an increased degree of radiological suspicion, with a detection rate of SigPCa of 29%. The mpMRI NPV during follow-up was 0.91. A suspicious mpMRI increases the reclassification and disease progression risk during follow-up and plays an important role in monitoring biopsies. In addition, a high NPV at mpMRI follow-up can help to decrease the need to monitor biopsies during AS.

Abstract P4-03-15: Does age affect outcome? Data from a large cohort from British Columbia, 2005-2014

Abstract Background Prior data has been conflicting about how age at diagnosis impacts patient outcomes and survival. Some studies suggest that younger age at diagnosis may negatively affect survival, independent of other disease characteristics. Accurate predictions of outcomes and patterns of relapse provide invaluable information to patients and help inform physician treatment recommendations, such as the role of extended adjuvant endocrine therapy. Purpose To determine the relapse free survival and overall survival data for all patients diagnosed with invasive breast cancer and treated at BC Cancer from 2005 to 2014. Methods Using the BC Cancer Breast Cancer Outcomes Unit (BCOU) database, we identified all patients referred with newly diagnosed invasive breast cancer at any stage between 2005 and 2014. For descriptive statistics, we analyzed clinical and pathological features at diagnosis and treatment specific variables compared across the following age cohorts: &amp;lt; 35, 35-39, 40-49, 50-59, 60-69, 70-79, and 80 years of age or more. To model the non-linear relationship of age at diagnosis as a continuous variable with the risk of relapse and death, we used an additive Cox proportional hazards model adjusting for subtype, LVI status, use of RT, chemotherapy, hormone therapy, and nodal status. We employed the fitted model to extract estimates for specific values of age while fixing other covariates at different values to create high and low risk cohorts. For subtypes Luminal B, HER2 positive and triple negative breast cancer, high-risk subgroups were defined as node-positive plus treatment with chemotherapy. Low risk was defined as Luminal A and node-negative. The extracted estimates were used to investigate the patterns of relapse among different ages via the means of adjusted cumulative incidence curves and to report the 10 year adjusted relapse free survival and overall survival estimates. Results We identified 24,469 patients who met the inclusion criteria with a median follow-up of 11.5 years. Patients &amp;lt; 35 and between 35-39 years of age were more likely to be diagnosed with breast cancer that was ductal histology, grade 3, LVI positive, HER2 positive, triple negative, and more advanced TNM stage at diagnosis. These younger patients were also more likely to undergo mastectomy, neoadjuvant and adjuvant chemotherapy compared to older age cohorts. Additive Cox proportional hazards revealed a statistically significant and clinically meaningful reduction in 10-year relapse free survival amongst patients with early-stage disease aged 30 and 35 as well as those aged 80, compared to patients aged 50 when adjusted for stage and treatment exposure. This was consistent across all high- and low-risk subgroups (Table 1). 10-year overall survival was significantly and meaningfully reduced in patients aged 30 and 80 compared to age 50 only amongst the high-risk patient populations. Conclusion Both younger and elderly age at breast cancer diagnosis were independent risk factors for poorer prognosis. To our knowledge, this is the largest patient cohort detailing such outcomes differences. Furthermore, this represents a more contemporary clinical context, compared to earlier publications. This work will help clinicians more accurately estimate disease trajectory, and may influence treatments recommendations. Other parameters for the entire cohort will be presented, including a more detailed identification and assessment of patient risk categories and its impact on outcomes. Table 1: 10 year estimates of relapse-free survival and overall survival age estimates by additive Cox proportional hazards model adjusting for subtype, LVI status, use of RT, chemotherapy, hormone therapy, and nodal status. Citation Format: Emily B. Jackson, Lovedeep Gondara, Caroline H. Speers, Karen Gelmon. Does age affect outcome? Data from a large cohort from British Columbia, 2005-2014 [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 P4-03-15.

Using Machine Learning to Develop a Predictive Model of Infant Hypoglycemia Based on Maternal and Infant Variables in an Electronic Health Record

All newborns experience low blood glucose levels when they first initiate carbohydrate metabolism. Some levels remain low, with potential seizures and severe brain injury. Predicting newborns at higher risk is clinically useful because newborns can have their blood sugar raised with breastfeeding, donor milk, formula, or oral dextrose gels. Additionally, informing parents of this higher risk can enhance shared decision-making in the first 48 hours after birth. To address this, we propose three predictive models using binary logistic regression for newborns receiving treatment with oral dextrose gels for hypoglycemia. The first is a parsimonious model, where a high-risk newborn's first blood glucose value is highly predictive of requiring an oral dextrose gel treatment. The second model can be used earlier in the clinical workflow. It is based on the most predictive variables that are also electronically available for all newborns and do not change much in the electronic health record. The third model explores the most predictive variables based on a conceptual model of factors associated with health disparities. These three models are informed from insights gleaned by an exploratory analysis of alternative outcome measures, variables, and threshold cutoffs using a standard heuristic of greedily finding the highest average difference for records on both sides of partitions. We discuss how the dynamics of when data are available during a hospital stay in the postnatal care unit for all patients impact the selection of useful variables for electronically-based decision support. We plan to modify handouts for postnatal care nurses that detail treatment guidance and support shared decision-making. We plan to embed stratified guidance, recommended scripts for high and low-risk cohorts, orientation materials for float and junior nurses, and patient-facing educational materials.

Can We Predict Length of Stay for CJR Patients Who Sustain a Displaced Femoral Neck Fracture?

AbstractThe Comprehensive Care for Joint Replacement (CJR) model holds hospitals financially accountable for the outcomes of patients undergoing hip and knee replacements. The purpose of this study is to see if a validated inpatient risk assessment tool can be used to predict patients with poor outcomes following hip arthroplasty. We hypothesize that the validated risk prediction tool (Score for Trauma Triage in the Geriatric and Middle-Aged [STTGMA]) can be modeled to stratify these patients at highest risk for poor outcomes at emergency department (ED) presentation. Between October 2018 and September 2020, 237 patients subject to the CJR bundle program were treated for a displaced femoral neck fracture with total hip arthroplasty or hemiarthroplasty and analyzed for demographics, comorbidities, injury details, and outcomes. A poor outcome was considered to be a longer length of inpatient hospital stay, venous thromboembolism (VTE), or readmission within 30, 60, or 90 days. Each patient's STTGMA score was calculated using their demographics, functional status, and injury details at time of ED admission. Patients were divided into risk quartiles based on STTGMA score. The top 25% risk cohort was compared against the bottom 25% risk cohort using chi-square or t-tests as appropriate. Mean STGGMA scores were 0.046 ± 0.028 in the highest risk cohort and 0.007 ± 0.001 in the lowest risk cohort. STTGMA was able to adequately risk stratify patients at risk for a longer length of inpatient hospital stay (p &lt; 0.01). The STTGMA tool was unable to risk stratify patients with postoperative VTE within 90 days (p = 0.986) or readmission within 90 days (p = 0.087). Providers can calculate STTGMA scores on admission for CJR patients to help identify which patients may require a longer length of inpatient hospital stay. These patients can be targeted with strategies to address these deficiencies.