Citations

The treatment landscape of invasive early-stage and metastatic breast cancer is evolving constantly. These NCCN Guidelines Insights focus on recent updates included in the most recent version (version 5.2025) of the NCCN Guidelines for Breast Cancer specific to workup, locoregional therapy, surveillance, and systemic neoadjuvant/adjuvant therapy recommendations for invasive, nonmetastatic breast cancer.

Abstract Background The associations between different types of diabetes, characterized by distinct pathophysiology and genetic architecture, and pancreatic ductal adenocarcinoma (PDAC) risk are not understood. Methods We investigated associations of genetic susceptibility to type 2 diabetes (T2D), 8 T2D mechanistic clusters, type 1 diabetes (T1D), and maturity-onset diabetes of the young (MODY) with PDAC risk. We used genome-wide association study (GWAS) summary-level statistics for T2D (242 283 cases, 1 569 734 controls), T1D (18 942 cases, 501 638 controls), and PDAC (10 244 cases and 360 535 controls) in individuals of European ancestry. Results Two-sample Mendelian randomization (MR) using the Robust Adjusted Profile Score (MR-RAPS) method indicated that genetically predicted T2D was associated with PDAC risk (OR = 1.10; 95% CI = 1.05 to 1.15), particularly the T2D obesity (OR = 1.28; 95% CI = 1.15 to 1.42) and lipodystrophy (OR = 1.25; 95% CI = 1.03 to 1.51) clusters. No association was observed for T1D with PDAC risk (OR = 1.01; 95% CI = 0.99 to 1.02). Pathway/gene-set analysis using the summary-based Adaptive Rank Truncated Product (sARTP) method revealed a significant association between the MODY gene-sets and PDAC risk (P = 1.5 × 10−8), which remained after excluding 20 known PDAC GWAS loci (P = 7.6 × 10−4). HNF1A, FOXA3, and HNF4A were the top contributing genes after excluding the previously identified GWAS loci regions. Conclusions Our results from this genetic association study support that T2D, particularly the obesity and lipodystrophy mechanistic clusters, and MODY genomic susceptibility regions play a role in the etiology of PDAC.

Abstract In recent years, various tracking technologies that work independently of imaging systems have been proposed to automate, simplify, and enhance various tasks in the brachytherapy treatment workflow. These tasks, critical to the overall accuracy of the therapeutic dose delivery, include applicator, catheter and needle insertion guidance, and reconstruction as well as transfer tube connection in afterloading technique. Task Group 317 was established as a joint American Association of Physicists in Medicine (AAPM) and European Society for Radiotherapy and Oncology (ESTRO) committee to review: the current state‐of‐the‐art scientific literature as it pertains to tracking technology in the field of brachytherapy; the benefits and issues related to the use of the technology for automated reconstruction of brachytherapy implants, quality control (QC) tasks such as channel path and tip reconstruction, and real‐time guidance tasks; their limitations, in particular in the clinical environment and, finally, to develop recommendations related to commissioning, quality assurance (QA) and clinical use. The Task Group has looked in detail at key tracking technologies in advanced brachytherapy applications: infrared, electromagnetic, fiber optic shape sensing (fiber Bragg grating), and active radiofrequency coil tracking. For each, the performance and accuracy in well‐controlled conditions as well as in clinically relevant environments are provided. Guidelines for clinical implementations, including target accuracy and performance needed for critical tasks, are summarized. Risk‐based analysis is discussed in the context of an electromagnetic‐based tracking system used as part of a clinical trial. The report concludes with the essential elements of an effective quality management program dedicated to the advanced features enabled by the above‐described technology.

Abstract Obesity has been associated with non‐Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome‐wide association studies of European ancestry ( N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist‐to‐hip ratio (WHR), and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05–1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (OR per SD = 1.12, 95% CI: 1.02–1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.

Objective: Describe changes in symptoms of velopharyngeal insufficiency (VPI)—hypernasality, audible nasal emission, and VPI-related quality of life—following LeFort I osteotomy in individuals with cleft palate +/- cleft lip. Design: Single-center, retrospective cohort study. Participants: Twenty-one patients with a history of cleft palate repaired in infancy were included in this study. Ten patients had no prior history of VPI surgery and eleven had a pharyngeal flap in place at the time of LeFort I osteotomy. The mean age at time of surgery was 17.2 years. Main Outcome Measure: Pre- and postoperative hypernasality severity, frequency of audible nasal emission, and total score on the VPI Effects on Life Outcomes youth questionnaire (VELO-Y) before and after LeFort osteotomy I. Fischer exact test was used to assess differences between groups for categorical variables and a t test was used for continuous variables. Results: Patients with no prior history of VPI management had a significant increase in hypernasality severity compared with those with a pharyngeal flap in place at the time of surgery ( P =0.004). Patients without a prior history of VPI management also had a significant increase in frequency of audible nasal emission, while patients with a pharyngeal flap had decreased audible nasal emission ( P =0.004). There was not a significant difference between groups for change in the total score on the VELO-Y ( P =0.16). Conclusions: Findings from this study may improve preoperative counseling provided to patients and caregivers on the risk of acquiring VPI after LeFort I osteotomy based on prior VPI surgical history.

SummaryIn individuals with high‐count monoclonal B‐cell lymphocytosis (MBL), we investigated if lymphadenopathy or splenomegaly found by imaging was associated with shorter time to first chronic lymphocytic leukaemia (CLL) therapy (TTFT) and overall survival (OS). Individuals with MBL seen at Mayo Clinic (2002–2019) were retrospectively divided into three cohorts based on imaging studies within 1 year of diagnosis: no imaging studies (Cohort A); imaging with no evidence of lymphadenopathy/splenomegaly (Cohort B); imaging with evidence of lymphadenopathy/splenomegaly (Cohort C). We compared baseline characteristics, TTFT and OS across the MBL cohorts to a cohort of individuals with small lymphocytic lymphoma (SLL). A total of 1078 patients were included: 640 with MBL and 438 with SLL. Compared to Cohort B, individuals in Cohort C were more likely to have unmutated immunoglobulin heavy chain variable region (IGHV) (43% vs. 25% p = 0.016), high‐risk fluorescence in situ hybridization (FISH) (del17p and del11q in 15% vs. 4%, p = 0.038) and higher expression of CD38 (31% vs. 16%; p = 0.011). After adjusting for sex and CLL‐International Prognostic Index (IPI), lymphadenopathy/splenomegaly was associated with a shorter TTFT (hazard ratio [HR] = 2.04, 95% confidence interval [CI]: 1.02–4.04, p = 0.042) but not OS (HR = 1.09, 95% CI: 0.62–1.92, p = 0.775). Lymphadenopathy/splenomegaly on imaging in individuals with high‐count MBL is associated with a more unfavourable risk profile and shorter time to first CLL‐directed therapy.

OBJECTIVE In many individuals, type 2 diabetes (T2D) remains poorly controlled despite taking multiple glucose-lowering therapies. Several studies have demonstrated that endogenous hypercortisolism is prevalent among these individuals. We tested whether cortisol-directed therapy improves their glycemic control. RESEARCH DESIGN AND METHODS In this prospective, multicenter, double-blind study, 136 individuals with T2D (hemoglobin A1c [HbA1c] 7.5%–11.5% [58–102 mmol/mol] on multiple medications) and hypercortisolism (by dexamethasone suppression test) were randomized 2:1 to the glucocorticoid receptor antagonist mifepristone (300–900 mg once daily; n = 91) or placebo (n = 45) for 24 weeks, with stratification by presence/absence of an adrenal imaging abnormality. The primary end point was the change in HbA1c. Secondary end points included changes in glucose-lowering medications, weight, and waist circumference and safety. RESULTS Mean baseline HbA1c in the study cohort was 8.55% (69.9 mmol/mol). At 24 weeks, the least squares mean (LSM) difference from placebo in HbA1c was −1.32% (95% CI −1.81 to −0.83; P < 0.001). Participants receiving mifepristone experienced reductions in body weight and waist circumference (placebo-adjusted LSM differences of −5.12 kg [95% CI −8.20 to −2.03] and −5.1 cm [−8.23 to −1.99], respectively). Of participants on mifepristone, 46% discontinued therapy, compared with 18% on placebo. Adverse events with mifepristone (>10% of participants) included hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness, consistent with mifepristone’s known tolerability profile. Increases in blood pressure also occurred. CONCLUSIONS In individuals with inadequately controlled T2D and hypercortisolism, cortisol-directed medical therapy with mifepristone reduced HbA1c, with a manageable tolerability profile.

Abstract Introduction A previously published case report suggested that alcohol might cause false-negative results in home sleep apnea testing (HSAT) utilizing Peripheral Arterial Tonometry (PAT). Alcohol is consumed by nearly a third of people globally. Based on this, along with rapid growth in PAT HSAT utilization, we aimed to prospectively study the interaction between alcohol consumption and PAT HSAT technology. We hypothesized that alcohol use would significantly attenuate sleep disordered breathing metrics in contrast to existing literature suggesting alcohol may exacerbate sleep apnea. Methods We planned to recruit subjects (N=100) from Mayo Clinic Arizona sleep clinic who were being evaluated for sleep-disordered breathing and elected to undergo home sleep apnea testing (WatchPAT ONE). Participants were required to report social alcohol use (no more than 1-3 drinks per day). The first and second home sleep apnea test were conducted on separate nights (night 1: without alcohol; night 2: with alcohol). Patients also completed a questionnaire, detailing their normal alcohol intake as well as intake during the respective sleep tests. Statistical analysis included paired sample t-test as well as a descriptive analysis. Results A total of 75 subjects were recruited (mean age [± SD] 56.8 ± 11.9; 90.7% male; mean BMI 29.8 ± 5.8) and 56 patients completed both sleep tests. The mean apnea hypopnea index (AHI) was not statistically different (p=0.784) between night 1 and night 2 (without alcohol: 19.6/hour ± 21.0; with alcohol: 19.3 ± 21.5, respectively). Similarly, no statistically significant difference was found in the AHI during REM and NREM sleep. Conclusion Preliminary data does not suggest a statistically significant difference in AHI without or with alcohol. While no significant change in AHI was observed, this study highlights the need for further investigation into the impact alcohol may have on PAT technology. Further analyses and data enrichment are underway. Support (if any) Mayo Foundation