Citations

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Acute Lymphoblastic Leukemia (ALL) were developed as a result of meetings convened by a multidisciplinary panel of pediatric ALL experts, with the goal of providing recommendations on standard treatment approaches based on current evidence. The NCCN Guidelines for pediatric ALL focus on risk assessment and stratification of risk-adapted therapy; treatment strategies for BCR::ABL1 (Philadelphia chromosome [Ph])-negative and BCR::ABL1-positive B-cell lineage, T-cell lineage, and infant ALL; and supportive care considerations. This selection from the NCCN Guidelines for pediatric ALL focuses on the diagnosis of and management of pediatric T-ALL.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses, as well as occult primary cancer, salivary gland cancer, and mucosal melanoma (MM). The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of nasopharynx cancer and ongoing research in this area.

Abstract Background: Waist circumference (WC) and its allometric counterpart, “a body shape index” (ABSI), are risk factors for colorectal cancer; however, it is uncertain whether associations with these body measurements are limited to specific molecular subtypes of the disease. Methods: Data from 2,772 colorectal cancer cases and 3,521 controls were pooled from four cohort studies within the Genetics and Epidemiology of Colorectal Cancer Consortium. Four molecular markers (BRAF mutation, KRAS mutation, CpG island methylator phenotype, and microsatellite instability) were analyzed individually and in combination (Jass types). Multivariable logistic and multinomial logistic models were used to assess the associations of WC and ABSI with overall colorectal cancer risk and, in case-only analyses, to evaluate heterogeneity by molecular subtype, respectively. Results: Higher WC (ORper 5 cm = 1.06, 95% confidence interval, 1.04–1.09) and ABSI (ORper 1-SD = 1.07, 95% confidence interval, 1.00–1.14) were associated with elevated colorectal cancer risk. There was no evidence of heterogeneity between the molecular subtypes. No difference was observed regarding the influence of WC and ABSI on the four major molecular markers in proximal colon, distal colon, and rectal cancers, as well as in early- and late-onset colorectal cancers. Associations did not differ in the Jass-type analysis. Conclusions: Higher WC and ABSI were associated with elevated colorectal cancer risk; however, they do not differentially influence all four major molecular mutations involved in colorectal carcinogenesis but underscore the importance of maintaining a healthy body weight in colorectal cancer prevention. Impact: The proposed results have potential utility in colorectal cancer prevention.

Abstract Aims Transcatheter mitral valve replacement (TMVR) has become a feasible alternative to surgical mitral valve replacement (SMVR) in selected patients at high surgical risk. The risk of valve thrombosis following SMVR and TMVR, and the optimal antithrombotic therapy following these procedures, remains uncertain. We aimed to compare the incidence of bioprosthetic mitral valve thrombosis (bMVT) after SMVR and TMVR, and the incidence of bMVT between patients on different antithrombotic regimens. Methods and results A literature search of Medline, Embase, and Cochrane Library was performed between January 2000 and August 2024. Random-effects models were used to derive pooled estimates of the incidence of bMVT in the absence of prior or active endocarditis and valve thrombosis. A total of 47 studies (6170 patients, total follow-up 9541.8 patient-years) were eligible for inclusion. The overall incidence of bMVT was 5.05 [95% confidence interval (CI) 3.18–8.01, I2 = 82%] per 100-patient-years. Subclinical bMVT was more common than clinically significant bMVT: incidence 19.11 vs. 7.91 per 100-patient-years, adjusted incidence rate ratio (aIRR) 4.62 (95% CI 1.39–15.36), P = 0.012. bMVT was numerically more common after TMVR than SMVR, but the comparison was not statistically significant: incidence 7.03 vs. 0.58 per 100-patient-years, aIRR 2.19 (95% CI 0.72–6.72), P = 0.170. Patients on vitamin-K antagonists (VKA) had a lower incidence of bMVT than patients on direct oral anticoagulants (DOAC; incidence 5.72 vs. 17.08, aIRR 0.31, 95% CI 0.13–0.73, P = 0.007). Conclusions bMVT is not uncommon, with numerically higher incidence in transcatheter compared to surgical valves, but the comparison was not statistically significant. VKAs are associated with a lower incidence of bMVT compared to DOACs.

366 Background: While improved survival has been previously demonstrated, the impact of immunotherapy on HRQoL in ESCC has not been well examined. Traditional PRO-based analyses in oncology trials, such as time to deterioration (TTD) and mixed models for repeated measures (MMRMs), are limited by discounting recurrent PRO events. Thus, we applied a 3-component joint model (JM) framework to define more clinically interpretable associations between patient-reported symptoms, treatment effects, and OS among subgroups of patients with ESCC from RATIONALE-306, which met its primary endpoint, with PD-L1 expression of ≥1%, ≥5%, and ≥10%. Methods: The final analytic sample included 226 patients in the tislelizumab + chemotherapy arm (T+C), 242 in the placebo + chemotherapy arm (P+C) for PD-L1 ≥1%, 113 in the T+C arm and 103 in the P+C arm for PD-L1 ≥5%, and 168 in the T+C arm and 178 in the P+C arm for PD-L1 ≥10%.From EORTC QLQ-C30 and OES18, 7 keysymptom domains were modeled (GHS, physical functioning, fatigue, dysphagia, pain, reflux, dietary restrictions). PRO data were collected at baseline and at every treatment cycle (up to 6 cycles), then every other cycle, and at safety follow-up, and change from baseline (CFBL) was analyzed. The joint model comprised three components: 1) linear mixed model predicting CFBL symptom scores; 2) Cox proportional hazard model (CPH) for time to OS; and 3) frailty (random effects for recurrent deterioration events [RDEs]) CPH model for time to PRO-based RDEs. Osoba (1998) 10-point threshold was used to define RDEs. Results: Adjusted completion rates were >90% in the ITT population for both arms. Significant T+C treatment effects wereobserved for physical functioning in PD-L1 ≥5% ( P =0.0476), and pain in PD-L1 ≥1% ( P =0.0028) and PD-L1 ≥5% ( P =0.0149) subgroups, but not in PD-L1 ≥10%. For other 5 symptoms (ie, GHS, fatigue, reflux, dysphagia, dietary restrictions), there were no statistically significant differences between treatment arms. However, T+C was associated with significant reductions in the risk of death across all 7 key symptoms and PD-L1 subgroups. As one example, with respect to interaction between pain and OS, T+C was associated with a 22% (HR, 0.78 [95% CI, 0.652-0.931]), 33% (HR, 0.67 [95% CI, 0.515-0.860]), and 47% (HR, 0.50 [95% CI, 0.344-0.720]) reduction in the risk of death in PD-L1 ≥1%, ≥5%, and ≥10%, respectively compared with P+C. Conclusions: In this analysis, the addition of tislelizumab to chemotherapy was associated with significantly less deterioration in multiple PRO symptoms including physical functioning and pain, alongside a lower risk of death, after adjusting for recurring deterioration events using a frailty model across multiple PD-L1 expression subgroups.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft tissue sarcoma and affects an estimated 1,500 people annually in the United States. DFSP frequently exhibits extensive local infiltration. Initial treatment is through surgical excision, and care should be taken to ensure that negative margins are achieved to minimize recurrence. Although DFSP has a reported high rate of recurrence, metastasis is more uncommon. Fibrosarcomatous DFSP is an aggressive variant with an increased risk for local recurrence and metastasis. If achieving negative margins or resection is not feasible, radiation therapy or systemic treatment are options that may be considered by a multidisciplinary team. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline recommended treatment options available for DFSP.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide criteria for selecting individuals for screening and offer recommendations for evaluating and managing lung nodules detected during initial and subsequent annual screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

AbstractBackgroundAlzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within the non‐Hispanic White (NHW) population. To address this, Accelerating Medicines Partnership in AD (AMP‐AD) aimed to promote inclusivity in multi‐omics AD research, to unravel unique molecular signatures and pathways. The study aimed to provide comprehensive insights into the proteomic landscape of AD across diverse racial groups.MethodDorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG) brain tissues were donated from multiple centers (Mayo Clinic, Emory University, Rush University, Mt. Sinai School of Medicine) and were harmonized through neuropathological evaluation, specifically adhering to the Braak staging and CERAD criteria. Among 1105 DLPFC tissue samples (980 unique individuals), 322 were from African American donors, 214 from Latino Americans, 551 from NHW donors, and the rest were from a mixed or unknown racial background. Among 280 STG samples, 86 were African American, 76 Latino American, 116 NHW and the rest were mixed or unknown ethnicity. All tissues were uniformly homogenized and analyzed by tandem mass tag‐based mass spectrometry (TMT‐MS). Following quality control (QC), proteins with more than 50% missing values were removed and iterative principal component analysis was conducted to remove outliers within brain regions. Differential protein expression was conducted within and across races after adjusting for batch using regression‐analysis.ResultIn total, 9,180 proteins from the DLPFC, and 9,734 proteins from STG brain tissues were quantified by TMT‐MS. Further analysis identified approximately 3,000 differentially abundant proteins in AD brains compared to controls within race. The AD‐associated differentially abundant proteins were strongly correlated between DLPFC and STG regions and with CERAD and Braak. Protein levels of MAPT and APP demonstrated equivalent disease‐related elevations in both African American and NHW individuals with AD. Notably, after adjusting for AD, significant differences in protein levels were identified across race.ConclusionThe proteomics approach employed by AMP‐AD sheds light on the brain proteome in AD across diverse racial groups, emphasizing the importance of inclusive research in establishing robust and generalizable discoveries. The identified proteins here could underscore racial disparities beyond disease association, contributing to a more nuanced understanding of AD pathophysiology.

Abstract Objective To evaluate the effectiveness of multiple decision aid strategies in promoting high quality shared decision making for prevention of stroke in patients with non-valvular atrial fibrillation. Design Cluster randomized controlled trial. Setting Six academic medical centers in the United States. Participants Patient participants were aged ≥18 with a diagnosis of non-valvular atrial fibrillation, at risk for stroke (CHA 2 DS 2 -VASc ≥1 for men, ≥2 for women), and scheduled for a clinical appointment to discuss stroke prevention strategies. Participating clinicians were those who manage stroke prevention strategies for participating patients. Intervention Patients were randomized to use a patient decision aid or usual care; clinicians were randomized to use an encounter decision aid or usual care with all participating patients. Main outcome measures Primary outcome measures were quality of shared decision making measured by OPTION12, knowledge of atrial fibrillation and its management, and decisional conflict. Results 1117 participants across six sites were included in the analysis. Compared with usual care, the combined use of both the patient decision aid and the encounter decision aid improved the quality of shared decision making (adjusted mean difference 12.1 (95% confidence interval (CI) 8.0 to 16.2; P<0.001), improved patients’ knowledge (odds ratio 1.68 (95% CI 1.35 to 2.09; P<0.001), and reduced patients’ decisional conflict (adjusted mean difference −6.3 (95% CI −9.6 to −3.1; P<0.001). Statistically significant improvements were also observed with the encounter decision aid alone versus usual care for all three outcomes and with the patient decision aid alone versus usual care for quality of shared decision making and knowledge. No important differences were observed in treatment choices for stroke prevention or in participants’ satisfaction. No statistically significant difference in the length of visit across study groups was detected. Conclusion Patients who received any decision aid (encounter decision aid, patient decision aid, or both) had lower decisional conflict, better shared decision making, and greater knowledge than those receiving no decision aid, except for the effect of the patient decision aid on decisional conflict, which did not reach statistical significance. The study establishes that use of either pre-visit or in-visit decision aids individually or in combination is advantageous compared with usual care. Trial registration ClinicalTrials.gov NCT04357288 .

AbstractBackgroundAlzheimer’s disease (AD) is a devastating neurodegenerative disorder with few therapies to treat, mitigate or prevent its onset. Understanding of this disease is predominantly based on research in non‐Hispanic Whites (NHW) although AD disproportionately affects African Americans (AA) and Latin Americans (LA), underrepresented in AD research. To address this knowledge gap, the Accelerating Medicine Partnership for Alzheimer’s Disease (AMP‐AD) Diversity Working Group was launched to generate multi‐omics data from post‐mortem brain tissue from donors of predominantly AA and LA descent. Here, we focus on genomic and transcriptomics measures, made available through the AD Knowledge Portal (ADKP).MethodBrain tissue from dorsolateral prefrontal cortex (DLPFC), caudate nucleus (CN), superior temporal gyrus (STG) and temporal pole (TP) regions of AA (N = 299), LA (N = 344) and NHW (N = 532) donors was obtained through Mayo Clinic, Mt. Sinai School of Medicine, Emory, Columbia, Rush Alzheimer’s Disease Center, Banner Sun Health, and 1Florida. DNA extracted from DLPFC tissue samples (n = 641) was utilized for whole genome sequencing (WGS) at New York Genome Center (NYGC). RNAseq of 2,224 samples was conducted either at Mayo, Rush or NYGC. Sequencing reads were processed through GenomeGPS and MAPRseq pipelines for WGS and RNAseq data, respectively. Following quality control (QC), RNAseq data was normalized and assessed for sources of variation (SOV). Integration of WGS and RNAseq data to perform comparative eQTL analysis across multi‐ethnic populations and brain regions is ongoing.ResultWGS data for 621 donors, and RNAseq data generated at Mayo (n = 1,136 samples), Rush (n = 627), and NYGC (n = 779) sequencing centers, were deposited to the ADKP. Consensus processing of RNAseq data revealed site, sex, race/ethnicity, RIN, AD diagnosis, age at death and/or library batch as SOV across various sites and brain regions. Principal component analysis of gene expression measures revealed no major stratification by disease or brain region. Accompanying clinical metadata of donors have been distributed through ADKP.ConclusionThese multi‐omics data made available to the research community is expected to be an initial step towards bridging our data and knowledge gap to elucidate conserved and distinct AD related pathways across these underrepresented at‐risk populations.