Citations

Background: Acute otitis media (AOM) is among the most common pediatric infections and a leading indication for antibiotic prescribing. Although current guidelines recommend 5 to 7 days of therapy for children 2 to 5 years of age with uncomplicated AOM, variation in antibiotic duration remains common. We evaluated whether a 5-day antibiotic course was associated with similar short-term outcomes compared with a 7-day course. Methods: We conducted a retrospective multicenter cohort study using electronic health record data from 44 pediatric emergency departments, urgent care centers, and primary care practices within an integrated health care system. Children 2 to 5 years of age with uncomplicated AOM treated with a single oral antibiotic during 2022 were included. The primary analysis compared children prescribed 5 versus 7 days of therapy. Treatment failure was defined as an AOM-related return encounter requiring a new systemic antibiotic prescription within 7 days after completion of therapy (EOT+7). Secondary analyses evaluated outcomes by antibiotic class and prespecified sensitivity analyses. Results: The final analytic cohort included 7528 children; 906 received 5-day therapy, and 1799 received 7-day therapy. Treatment failure occurred in 0.44% and 0.61%, respectively (absolute risk difference: −0.17%; 95% CI: −0.73 to 0.39; risk ratio: 0.72; 95% CI: 0.23-2.26). Findings were consistent across antibiotic-specific and sensitivity analyses. Conclusions: Among children 2 to 5 years of age with uncomplicated AOM, a 5-day antibiotic course was not associated with an increased risk of short-term treatment failure compared with a 7-day course, supporting guideline-concordant prescribing and outpatient antimicrobial stewardship.

Background: The current guidelines recommend that women at elevated risk for breast cancer (BC), defined as lifetime BC risk ≥ 20%, undergo annual screening with breast magnetic resonance imaging (MRI) and mammogram. However, limited evidence exists in the literature to guide the optimal timing of the MRI relative to the mammogram. Our study evaluated women undergoing high-risk BC screenings to determine the impact of timing for supplemental MRI on BC detection. Methods: Patients who completed high-risk screening MRI at a single institution from January 2019 through June 2022 were included. Baseline characteristics and clinical outcomes were collected through retrospective chart review. MRI exams were divided into two groups based on timing of MRI: concurrent (<90 days from mammogram) and staggered (≥90 days from mammogram). Results: Of 1115 patients initially identified, 770 met inclusion criteria, with a total of 3707 screening exams performed (2073 mammograms and 1634 MRIs). The final analysis included 1355 MRI exams for 712 patients, where a prior mammogram and MRI were available. Of the MRIs included, 784 (57.9%) were concurrent and 571 (42.1%) were staggered. Additional imaging was performed for 12.5% (98/784) of concurrent MRIs and 9.6% (55/571) of staggered MRIs. Biopsy rates were 9.8% (77/784) for concurrent and 7.0% (40/571) for staggered MRIs. In this high-risk population, there were surprisingly low BC detection rates, with a BC incremental detection rate of 0.5% in both the concurrent and staggered groups (p = 1.0), with the median size of detected invasive BCs equaling 5 mm in the concurrent group and 4 mm in the staggered group (p = 0.72). Conclusions: When comparing concurrent and staggered MRI regimens, there were no significant differences in incremental cancer detection rate, tumor size, rates of additional imaging, or negative biopsies. Further investigation with prospective analysis is needed to validate these findings.

564 Background: HER2+ ILC is rare (~5% of ILC), with limited data on long-term adjuvant trastuzumab outcomes. We investigated late recurrence and immune landscapes of HER2+ ILC vs invasive ductal carcinoma (IDC) in the phase III NCCTG N9831 trial (NCT00005970) and a real-world cohort. Methods: We evaluated 3304 early-stage HER2+ breast cancer patients (pts) enrolled in N9831 (122 ILC, 3182 IDC). Recurrence-free survival (RFS) and overall survival (OS) were estimated (Kaplan-Meier) and compared using multivariable Cox regression adjusting for age, tumor size, grade, hormone receptor (HR), and nodal status. Findings were validated in a real-world cohort of HER2+ pts (Caris Life Sciences CODEai platform). Immune microenvironments were profiled by WTS deconvolution (Quantiseq). Real-world overall survival was calculated from trastuzumab start to last contact. Results: In N9831, ILC pts were older (median 54 vs 49 y), more ER+ (74.6% vs 51.4%), and had more N3 disease (25.4% vs 12.7%) compared to IDC. ILC pts derived a comparable magnitude of benefit from adjuvant trastuzumab compared to the overall population (HR 0.58 vs 0.67). However, long-term outcomes diverged: while the 5-year RFS was similar (77.1% vs 82.7%), ILC pts experienced a steep decline between years 5-15 (77.1% to 57.7%; ~20% decline) vs IDC (82.7% to 72.7%; ~10% decline) after multivariable Cox analysis (Table). In the real-world early/advanced cohort (n=1328; 26 ILC vs 1302 non-ILC [subset IDC n=595]) treated with trastuzumab-based therapy, ILC pts had worse mOS (33.7 vs 68.6 m, HR 2.01, 95%CI 1.00-4.07, p=0.04) compared to non-ILC. However, there was no statistically significant difference when compared specifically to IDC (HR 1.77, 95% CI 0.87-3.61, p=0.11). ILC had: i) numerically lower tumor mutation burden (TMB)-high (4.2% vs 9.5%, p=0.38); ii) higher infiltration of B cells, Tregs, and M2 macrophages (p<0.05); iii) upregulated MHC class II expression (HLA-DOA, p<0.05); and iv) downregulated proliferative and DNA repair pathways (E2F, G2M, MYC; FDR <0.25) compared to non-ILC. Conclusions: HER2+ ILC carries late recurrence risk despite initial trastuzumab benefit. The unique immune landscape (Treg/M2 macrophage enrichment and lower proliferative signatures) distinguishes HER2+ ILC from IDC, highlighting the need for tailored strategies. Long-term RFS and OS in HER2-positive ILC vs IDC (N9831 trial). Population N 5-year% (95% CI) 10-year% (95% CI) 15-year% (95% CI) ILC 122 RFS 77.13% (69.9, 85.1) OS 84.04% (77.7, 90.9) RFS 70.57% (62.7, 79.4) OS 76.0% (68.7, 84.2) RFS 57.67% (44.2, 75.1) OS 65.22% (56.6, 75.2) IDC 3182 RFS 82.71% (81.4, 84.1) OS 90.18% (89.1, 91.2) RFS 77.45% (75.9, 78.9) OS 81.81% (80.4, 83.2) RFS 72.68% (70.77, 74.6) OS 76.68% (75, 78.4)

This guideline has been updated. This ASCO Living Guideline is reviewed on an eight-week cycle. Please see the online dynamic version for the latest updates. Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information ( Appendix 1 and Appendix 2 ). Updates are published regularly and can be found on the ASCO Publications website .

Measurable residual disease (MRD) has established prognostic significance in patients with myeloid disorders; however, there is limited data regarding its prognostic and predictive value and the optimal technique for measurement in the setting of post allogeneic hematopoietic cell transplantation (allo-HCT). A multi-gene next generation sequencing (NGS) panel can overcome the limitations of conventional techniques for measurement of MRD and can shed light onto the longitudinal evolution and genomic complexity of patients undergoing allo-HCT for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In this study, patients with AML or MDS who underwent their first allo-HCT and completed NGS testing at day +100 and were in a state of morphological remission were identified from the transplant registry of Mayo Clinic in Florida. The primary aim was to evaluate the prognostic impact of somatic variants detected via NGS at day +100 post allo-HCT on long-term outcomes. In total, 105 patients who underwent allo-HCT for AML and MDS and completed NGS testing on day +100 were included in the study population. Seventeen patients were found to have detectable variants, and 88 patients were without a detectable variant. At a median follow up of 1.4 years (0.1–5.5), presence of any variant at day +100 was associated with inferior 4-year overall survival (OS) (32% vs. 69%, P < 0.001), decreased progression free survival (PFS) (34% vs. 61%, P < 0.001), and a higher incidence of relapse (64% vs. 23%, P < 0.001). In univariate models, a lower Karnofsky performance score and presence of variants post allo-HCT remained significantly associated with inferior OS, higher relapse incidence, and a decreased PFS. The presence of variants at day +100 post allo-HCT remained significant in multivariate models for relapse ( P = 0.002) but not for OS ( P = 0.06) and PFS ( P = 0.08). These results indicate that the presence of detectable somatic variants at day +100 is associated with poor long-term outcomes and are predictive of a higher incidence of relapse.

Abstract Background Abdominal arterial calcification is a well-established predictor of cardiovascular events and mortality in kidney failure. Autosomal dominant polycystic kidney disease (ADPKD), a common genetic cause of kidney failure, presents with a distinct vascular profile. However, the burden of abdominal arterial calcification in ADPKD remains inadequately characterized. Clarifying these differences may improve cardiovascular risk stratification and transplant timing. Methods We conducted a retrospective cohort study of 4088 adult patients listed for kidney transplant at three Mayo Clinic sites (2005–2024). Patients were categorized by kidney failure cause: ADPKD vs. non-ADPKD. Abdominal arterial calcification was quantified on non-contrast computed tomography (CT) scans using a modified Agatston scoring method. Propensity score matching (1:1) adjusted for age, sex, race, lipid levels, left ventricular ejection fraction, dialysis exposure, coronary artery disease, neurovascular disease, and smoking history, was performed. Abdominal arterial calcification scores were compared between matched groups, and subgroup analyses evaluated abdominal arterial calcification severity across dialysis durations in ADPKD patients. Results After matching, 309 patients with ADPKD were compared with 309 non-ADPKD chronic kidney disease (CKD) controls. Abdominal arterial calcification scores were significantly lower in the ADPKD group (median: 425.3; IQR: 0.0–2033.5) than in the non-ADPKD group (median: 1256.8; IQR: 96.5–5033.8). Among ADPKD patients, abdominal arterial calcification scores increased with dialysis duration (P &lt; .001). Conclusion ADPKD patients exhibit lower abdominal arterial calcification scores than their non-ADPKD counterparts after adjusting for clinical variables. Abdominal arterial calcification progression with dialysis highlights the importance of early transplant evaluation. This study introduces a novel adaptation of coronary calcium scoring software for quantifying abdominal calcification, offering a standardized approach to vascular risk assessment in kidney transplant candidates.

ABSTRACT 162 patients with relapsed secondary central nervous system lymphoma (R‐SCNSL) (median age, 65 years; male, 59.9%) including central nervous system (CNS)‐only ( n = 120) and concomitant CNS/systemic relapse ( n = 42) were retrospectively analyzed. Overall, 21.9% of patients were classified as high risk according to the CNS International Prognostic Index (CNS‐IPI). Several biological and clinical features were significantly associated with leptomeningeal involvement, including double‐ or triple‐hit (DHL/THL) status, MYC rearrangement, negative BCL6 expression by IHC, bone marrow involvement, and concomitant R‐SCNSL. Multivariable analysis showed that leptomeningeal involvement independently predicted inferior OS and was associated with a 98% increase in the hazard of death compared with parenchymal relapse (HR = 1.98, 95% CI: 1.20–3.26, p = 0.008). Based on anatomical localization, R‐SCNSL was classified into four subtypes: parenchymal‐only involvement (parenchymal‐CNS [P‐CNS], 68/42%) and parenchymal involvement plus systemic relapse (parenchymal‐concomitant [P‐concomitant], 17/10.5%); and leptomeningeal with or without parenchymal involvement (leptomeningeal‐CNS [LM‐CNS], 52/32.1%) and leptomeningeal with systemic relapse (leptomeningeal‐concomitant [LM‐concomitant], 25/15.4%). This anatomical classification significantly impacted OS and PFS ( p < 0.001). Two‐year OS and PFS were 58.2% and 29.1% for P‐CNS, 32.4% and 17.7% for P‐concomitant, 22% and 13.9% for LM‐CNS, and 7.1% and 0% for LM‐concomitant, respectively. ASCT showed a trend toward improved survival among patients with a response (CR/PR) in a 4‐month landmark analysis. These findings support the clinical application of the anatomical classification in the management of R‐SCNSL.

Background Vocal cord dysfunction (VCD) is an underrecognized differential diagnosis for asthma and is often influenced by psychological factors. The COVID-19 pandemic introduced new stressors and disrupted access to pediatric care, potentially affecting VCD incidence and recognition. Objectives This study aimed to determine whether the incidence of pediatric VCD at Nemours Children's Hospital in Orlando changed during the COVID-19 pandemic and to identify psychological diagnoses most associated with VCD. Methods A retrospective chart review was conducted for patients diagnosed with VCD between January 2017 and July 2022, including 2.5 years before and 2.5 years during the pandemic. Demographics, diagnostic methods, triggers, comorbidities, and psychological conditions were extracted from the electronic medical record. Results Among 74,022 patients (45,199 pre-pandemic; 28,823 pandemic), VCD incidence significantly decreased during the pandemic (0.7% vs. 0.3%, p &lt; 0.001). Psychological diagnoses also declined modestly: anxiety (2.6% vs. 2.0%), depression (0.3% vs. 0.2%), and ADHD (4.4% vs. 3.5%). Compared with non-VCD patients, those with VCD were older (median 14 vs. 9 years), predominantly female (71% vs. 47%), and more often White/non-Hispanic. They had higher rates of asthma (41% vs. 16%), allergic rhinitis (20% vs. 11%), gastroesophageal reflux (31% vs. 4%), and psychological conditions, including anxiety (8.5% vs. 2.3%), depression (1.5% vs. 0.2%), and panic attacks (0.8% vs. 0.1%). Conclusions In contrast to prior reports, VCD incidence declined during the pandemic, likely reflecting reduced healthcare access or underdiagnosis. Persistent associations with psychological conditions highlight the biopsychosocial nature of VCD and the importance of multidisciplinary evaluation in pediatric populations.

Background While SARS-CoV-2 vaccines are highly effective in healthy individuals, the magnitude and durability of humoral and cellular responses in patients with solid malignancies receiving chemotherapy remain understudied. Previous reports suggest that patients with cancer may not mount adequate immune response after SARS-CoV-2 vaccination. Additionally, most studies focused on humoral responses, while data regarding cellular immune responses are scarce. In this study, we evaluated humoral and cellular responses in patients with solid tumors receiving chemotherapy compared to healthy individuals up to one year after vaccinations. Methods Patients aged ≥18 who were willing to receive the SARS-CoV-2 vaccine were enrolled. Anti-SARS-CoV-2 immunoassays were used to detect antibodies against nucleocapsid and spike proteins. Human IFN-γ Fluorospot assay was used to determine antigen−specific T-cell responses. Data were compared between groups using Mann−Whitney test for continuous variables and Fisher’s exact test for categorical variables. Results A total of 67 subjects (47 patients with cancer and 20 healthy individuals) were included. 1–3 months following the second vaccine doses, 96% of patients with cancer and 100% of healthy individuals demonstrated a positive humoral response. While the positivity rate was not significantly different, patients with cancer had significantly lower spike IgG antibodies than healthy individuals. However, this difference diminished at 6 months when patients with cancer had increased antibodies compared to decreased antibodies in the healthy cohort and no difference was noticed at 12-month. Patients with cancer developed a similar antigen-specific T-cell response as healthy individuals at 1–3 months, 6 months and 12 months. There were no significant differences when comparing patients aged ≤ 55 years vs. &gt;55 years, stages I-III vs. IV, single vs. multiple chemotherapy, and BNT162b2 vs. mRNA-1273 vaccines. There was a significant moderate correlation between neutralization and antibody levels at 12 months. However, despite patients with cancer having a significantly higher COVID risk score, there were no significant differences in COVID-19 infection and hospitalization between patients with cancer and healthy individuals. Conclusion Despite initial impaired antibody responses to SARS-CoV-2 vaccinations, patients with solid malignancies receiving chemotherapy effectively generated long-term cellular and humoral responses by 6 and 12 months, leading to similar infection and hospitalization rates compared to healthy individuals.