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Importance Patients with cancer have high utilization of health care services, and many have high financial burdens from care. High-deductible health plans (HDHPs), which offer lower premiums at the expense of higher deductibles and possibly higher out-of-pocket costs, are associated with decreased care utilization among survivors of cancer. However, it is unclear whether HDHPs are associated with cancer outcomes. Objective To determine whether HDHP status is associated with survival among cancer survivors and individuals without history of cancer and whether financial barriers to care mediate associations between HDHP status and survival. Design, Setting, and Participants This cross-sectional study included US adults ages 18 to 84 years who participated in the National Health Interview Survey from 2011 to 2018. Data were analyzed from December 14, 2023, to December 1, 2025. Exposure HDHP status. Main Outcomes and Measures Outcomes of interest were overall survival (OS) and cancer-specific survival (CSS). Analyses were adjusted for insurance status, marital status, sex, comorbidities, education, household income, geographic region, and cancer site and time since cancer diagnosis (if applicable). Results A total of 147 254 respondents (mean [SD] age, 45.7 [16.4] years; 79 261 [50.9%] female) were identified, including 9799 (5.9%) with history of cancer. A total of 2331 cancer survivors (25.6%) and 37 473 individuals without history of cancer (28.5%) reported an HDHP at the time of NHIS participation. HDHP status was associated with worse OS (hazard ratio [HR], 1.46; 95% CI, 1.19-1.79) and CSS (HR, 1.34; 95% CI, 1.01-1.77) among cancer survivors. In contrast, among adults without history of cancer, HDHP status was not significantly associated with OS (HR, 1.08; 95% CI, 0.96-1.21; P for interaction = .001). In mediation analyses, HDHP status among cancer survivors was associated with increased financial barriers to care, which mediated approximately 30% to 70% of the total association of HDHP with survival. Conclusions and Relevance In this cross-sectional study of nationwide population-based data, HDHPs were associated with worse OS and CSS among cancer survivors. However, HDHPs were not associated with mortality in adults without history of cancer. These data suggest that insurance coverage that financially discourages medical care may financially discourage necessary care and ultimately worsen cancer outcomes.

Abstract Background Computed tomography (CT) is an essential imaging modality for disease diagnosis, treatment efficacy, and image‐based guidance of various medical procedures. The locally deposited radiation dose in tissues, as estimated by the computed tomography dose index (CTDI), can vary considerably across exposures delivered by CT scanners from different vendors, even if the scans are performed using similar technique factors, such as tube potential and tube current. The volumetric CTDI (CTDI vol ) is a common dose metric that reports an average radiation dose (in mGy) delivered to a specific volume within a test phantom. The CTDI vol is important in dosimetry applications as the organ absorbed dose within the patient has been shown to scale in near‐linear proportion, creating a basis for comparing organ doses across different scan protocols and scanner models. Purpose To develop a database of tube current‐time product (mAs) normalized CTDI vol values for currently utilized CT scanner models for each of the four primary CT vendors for use in the MIRDct organ dosimetry software available at MIRDsoft.org. This data forms the basis of the MIRDct code, which reports organ doses across a range of computational phantoms based upon axial organ dose coefficient libraries generated through Monte Carlo radiation transport for a reference CT scanner. Organ doses delivered by alternate CT scanner vendors and models may then be reported using ratios of normalized CTDI vol values under similar technique factors. Methods Scanners were selected from four major CT manufacturers: Philips Healthcare, GE Healthcare, Canon Medical Systems, and Siemens Healthineers. Technique parameters were also selected for each scanner that closely matched values used in the generation of an equivalent CT source term (small to large bowtie filters; 80–140‐kVp tube voltage; and 10‐mm to 40‐mm beam collimation). For each scanner chosen, the appropriate technique factors and protocols were selected, and the console‐reported CTDI vol values were recorded and normalized to a set value of 100 mAs. The normalized CTDI vol data collected for use within the MIRDct code were analyzed for noticeable patterns, features, and trends, and were compared to similar normalized CTDI vol datasets used within the National Cancer Institute NCICT software and the Virtual Phantoms, Inc. VirtualDose software. Results For all given CT scanner and technique factor combinations, there was strong agreement in normalized CTDI vol values across all three codes: between 0% and 12% difference for the compared scanners. Ratios of CTDI vol values for various CT scanner vendors and models to the corresponding CTDI vol values for the MIRDct reference scanner (Cannon Aquilion One Genesis) were also compared on the basis of either the 16‐cm head PMMA phantom or the 32‐cm body PMMA phantom. The mean quotient of these normalized CTDI vol ratios (head ratios to body ratios) was found to be approximately 1.06, and thus either ratio may be applied in reporting patient organ dose by MIRDct. Conclusions A database of normalized CTDI vol (mGy/100 mAs) was created for 17 models of CT scanners from four manufacturers at varying tube potentials, collimations, x‐ray bowtie filters, and phantom sizes for use in the MIRDct software.

Abstract Recent updates to monocyte count thresholds recognize oligomonocytic chronic myelomonocytic leukemia (OM-CMML) as an early form of CMML. However, the clinical validity of these changes remains uncertain without incorporating biological and genomic factors. In this study, we analyzed a cohort of 911 patients (249 with OM-CMML, 359 with overt CMML, and 303 with myelodysplastic syndromes) using unsupervised clustering to evaluate the role of genomic determinants in refining CMML diagnosis. Our findings show that CMML molecular signatures (biallelic TET2 mutations or SRSF2-TET2 comutations) are linked to a distinct transcriptome, monocytic bias, classical monocytosis, and a higher risk of progression to overt CMML in OM-CMML cases. We developed a weighted genomic model and diagnostic workflow showing that combining genomic signatures with bone marrow monocyte frequencies in OM-CMML more accurately predicts progression to overt CMML. These findings support integrating genomic determinants and our clinic-ready diagnostic workflow into the CMML diagnostic framework to improve accuracy. Significance: Through comprehensive clinical and genomic profiling of a large patient cohort, alongside immunophenotypic and transcriptional cellular analyses, this study provides evidence that incorporating genomic determinants into the diagnostic criteria for OM-CMML improves diagnostic accuracy and refines the identification of early-stage CMML, thereby preventing misclassification.

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.

Abstract Cancer occurs in ∼1 per 1000 pregnancies; thousands of patients may require radiation procedures for diagnosis and treatment each year in the United States alone. This rare but high-risk scenario, coupled with fear of radiation, has created ambiguity in the ideal management of pregnant patients. Without a comprehensive guide for the use of radiation in imaging and treatment for pregnant cancer patients, it is difficult for providers to offer optimal patient-centered care without introducing disparities. The goal of this paper is to provide guidance on the use of radiation for screening, diagnosis, staging, and treatment of cancer, while highlighting gaps in existing knowledge and guidelines. The intention is that physicians, medical physicists, and patients could use this document as a resource for shared decision-making, ensuring safe and effective practice. A team of physicians and medical physicists with expertise in imaging, radiotherapy, and maternal fetal medicine was assembled, along with a patient advocate and lawyer. Existing guidelines and recent literature were reviewed. Authors also drew from their experience where published guidance was lacking. The resulting document discusses best practice to guide use of radiation for cancer, as well as patient-centered care management and legal considerations. Overall, it is possible to safely and effectively deliver radiation to pregnant patients in numerous circumstances. Use of radiation or other modalities should be discussed through shared decision-making with the physician and patient, contextualizing the maternal and fetal risk from treatments. Healthcare providers should support wide access to reproductive healthcare to allow equitable, evidence-based, patient-centered healthcare.

Abstract Background Polycystic ovary syndrome (PCOS) affects 10% to 13% of individuals assigned female at birth (AFAB), although a greater prevalence is reported in transgender/gender diverse individuals (TGD) (23.8-38.8%). Testosterone therapy (TT) in TGD individuals is linked to worsening cardiovascular risk factors (CVRFs). Whether TT induces more adverse cardiometabolic changes in TGD with PCOS than TGD without PCOS remains uncertain. Objective To compare the effects of TT on CVRF in TGD with and without PCOS. Methods We retrospectively reviewed 373 records to identify 62 TGD with PCOS (withestablished guideline criteria) and 132 age-matched TGD without PCOS. Data included longitudinal anthropometric measurements, hormone and metabolic parameters, and CVRF before and after TT. Group comparison of PCOS vs without PCOS before and after TT was conducted via independent t-tests, Mann–Whitney-U, and Chi-square. Results At baseline, TGD with PCOS had significantly greater body mass index (BMI), obesity prevalence, and, after controlling for BMI, baseline metformin use. There were no significant differences between TGD with and without PCOS when comparing intra-participant changes after TT. Controlling for BMI, TGD with PCOS on TT exhibited significantly greater hyperlipidemia prevalence, alanine transaminase (ALT) levels, and bioavailable testosterone concentrations than TGD without PCOS on TT. Conclusion Greater baseline cardiometabolic risk was largely BMI-related in TGD with PCOS compared to TGD without PCOS. Only hyperlipidemia and elevated ALT were more prevalent during TT after adjusting for BMI. These findings support cardiometabolic monitoring during TT in all TGD individuals without significant increased risk with PCOS history.

PURPOSE There is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs. METHODS Using the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) a two-round international multistakeholder Delphi survey (N = 109 in Round 1 [October 2024]; N = 96 in Round 2 [December 2024]); and (4) an independently chaired virtual consensus meeting (N = 31; January 2025) where multidisciplinary, international experts reviewed and voted to finalize items for inclusion. RESULTS Consensus was reached on six recommendations emphasizing three core PRO tolerability concepts: overall side effect impact, symptomatic adverse events, and overall health-related quality of life. The integration of PROs to inform final dose recommendations in dose escalation and optimization trials should be considered, regardless of trial design. The recommendations highlight the importance of PRO data analysis over time and across dose levels, defining PRO research objectives as descriptive or statistically powered, and assessing PRO-related end points to guide end point selection for subsequent studies. CONCLUSION This foundational guidance outlines key PRO research objectives in DFOTs. By facilitating the systematic integration of PROs, this guidance supports the utilization of patient-centered evidence for the tolerability and efficacy assessment of therapies to inform dose escalation, optimization, and regulatory evaluation—ultimately contributing to the development of safer, more effective therapies.

Background: For women in the United States desiring implant-based breast reconstruction, the maximum volume of commercially available silicone breast implants has, to date, been 800 cc. The authors evaluated the safety of Mentor larger-size MemoryGel Ultra-High Profile breast implants (≥930 cc) in women undergoing postmastectomy breast reconstruction. Methods: This 10-year, multicenter, open-label, prospective, investigational study assessed the safety and effectiveness of larger-volume implants in women undergoing postmastectomy 2-stage primary or revision reconstruction. Three-year Kaplan-Meier curves and multivariable Cox regression analyzed the association between patient and treatment characteristics and surgical outcomes. The BREAST-Q was used to assess effectiveness at 3 years. Results: A total of 400 women were enrolled (225 primary and 175 revision reconstruction). Mean body mass index was 35.8 kg/m 2 ; 81% had a body mass index greater than or equal to 30 kg/m 2 . At 3 years, the cumulative incidence of postoperative complications (excluding rupture) was 63.0% (95% confidence interval, 58.1% to 67.9%). The reoperation rate was 24.5% (95% CI, 20.4% to 29.1%), and the explantation rate was 15.8% (95% CI, 23.5% to 19.9%). Independent predictors of complications included radiation therapy and a history of smoking. There were no significant associations between postoperative complications and implant volume greater than or equal to 1135 cc or less than 1135 cc. BREAST-Q scores at year 3 showed significant improvements from baseline in Satisfaction with Breasts, Psychosocial Well-Being, Sexual Well-Being, and Physical Well-Being (all P < 0.0001). The mean score for Satisfaction with Outcome was 79.9. Conclusions: These 3-year results demonstrate that larger-volume silicone breast implants represent a safe and effective option for patients with larger breasts who are requesting postmastectomy implant-based reconstruction.

ABSTRACT Background While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune‐related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs. Methods A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as monotherapy or in combination, and had HLA typing available. This analysis spans from 2003 to 2023 with a focus on cutaneous irAEs. Statistical analyses were conducted to assess the association between HLA alleles and irAEs. Results Our analysis revealed that the HLA‐B*51:01 allele was associated with a higher risk of cutaneous irAEs after adjusting for ICI regimen (hazard ratio: 1.71 [95% CI, 1.12–2.61], p = .013.) Conclusion This is the largest study to link an HLA allele with ICI‐induced cutaneous irAEs. The findings may support the use of HLA typing as an initial screen for developing irAEs, providing a simple, straightforward metric that can be rapidly performed on patients prior to initiation of ICIs. However, further research is needed across different cancer and toxicity types.