Recent ucsdsom_ram_oapdeposits items

Metformin Is Associated With Reduced Odds for Colorectal Cancer Among Persons With Diabetes

Wed, 17 Jun 2026 00:00:00 +0000

INTRODUCTION: Metformin may be associated with reduced colorectal cancer (CRC) risk, but findings from previous studies have been inconsistent and had insufficient sample sizes to examine whether the association differs by anatomic site. This study examined whether metformin was associated with reduced CRC risk, both overall and stratified by anatomic site, in a large sample of persons with diabetes who underwent colonoscopy. METHODS: We performed a case-control study of US Veterans with prevalent diabetes who underwent colonoscopy between 1999 and 2014 using Department of Veterans Affairs electronic health record data. Cases were defined by presence of CRC at colonoscopy, while controls had normal colonoscopy. The primary exposure was metformin use at time of colonoscopy (yes/no). Association of metformin exposure with CRC (further stratified by proximal, distal, or rectal subsite) was examined using multivariable and multinomial logistic regression and summarized by odds ratios...

Larry and the Contraband Lo Mein

Wed, 10 Jun 2026 00:00:00 +0000

Larry and the Contraband Lo Mein

Radiation-Induced Volume Changes in the Parotid and Submandibular Glands, Intra-Gland Dose Distribution, and Quality of Life Scores Over a Long Follow-Up Period

Sun, 7 Jun 2026 00:00:00 +0000

Purpose Xerostomia remains a common toxicity following head and neck radiotherapy (RT) that significantly impacts patients' quality of life (QOL). Although intensity-modulated RT reduces the dose to the salivary glands, many patients still experience salivary gland toxicity. Methods and Materials This study examined the association between radiation-induced volume changes in the parotid and submandibular glands, mean dose to the salivary glands, and intra-gland dose distribution, as well as its relationship to QOL scores, over a median follow-up period of 47 months. Results Analysis of 329 patients using a linear mixed-effects model revealed distinct volume change patterns. The parotid glands initially underwent significant volume reduction but subsequently showed dose-dependent recovery, increasing in volume by an average rate of 2.4% per doubling of time. This recovery was negatively impacted by higher age and poor performance status. Conversely, the submandibular glands gradually...

Analysis of more than 400,000 women provides case-control evidence for BRCA1 and BRCA2 variant classification

Thu, 4 Jun 2026 00:00:00 +0000

Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS, and previous findings indicate that case-control likelihood ratios (LRs) outperform odds ratios for variant classification. As an initiative of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Analytical Working Group we analyzed germline sequencing data of BRCA1 and BRCA2 from 96,691 female breast cancer cases and 303,925 unaffected controls from three studies: the BRIDGES study of the Breast Cancer Association Consortium, the Cancer Risk Estimates Related to Susceptibility consortium, and the UK Biobank. We observed 11,227 BRCA1 and BRCA2 variants, with 6,921 being coding, covering 23.4% of BRCA1...

A learning-driven automatic planning framework for proton PBS treatments of H&N cancers

Fri, 24 Apr 2026 00:00:00 +0000

Purpose Proton pencil beam scanning (PBS) treatment planning for head & neck (H&N) cancers involves numerous conflicting objectives, requiring iterative objective parameter adjustments to balance multiple clinical goals. We propose a learning-driven inverse optimizer and integrate it into a proximal policy optimization (PPO)-based planning framework to automatically generate high-quality plans for patients with diverse treatment requirements. Methods and Materials The inverse optimizer is a learning-to-optimize (L2O) method that predicts update steps by learning from task-specific data distributions. For the first time, long-context processing techniques developed for large language models (LLMs) are utilized to address the scalability limitations of existing L2O methods, enabling simultaneous optimization over a substantially large set of variables. The PPO framework functions as an outer-loop virtual planner, autonomously adjusting objective parameters through a policy...

The 21st century marks a rise in TURP retreatment rates: an analysis of Veterans Health Administration data

Tue, 25 Nov 2025 00:00:00 +0000

PurposeWith the advent of new and emerging procedures for benign prostatic hyperplasia (BPH), as well as a greater reliance on medical therapies, trainees may be receiving less exposure to the longstanding gold standard of treatment, transurethral resection of the prostate (TURP). Although TURP outcomes are generally durable, success rates vary. We sought to perform a descriptive analysis of temporal trends in TURP outcomes, evaluating whether those performed prior to 2001 were less likely to require re-operation compared to more contemporary TURP procedures.MethodsWe accessed the Veteran’s Affairs (VA) national repository of electronic medical record data. We included veteran males with no prior BPH surgery who received a TURP. We used billing codes to determine retreatment and complications rates within 5 years of TURP. Outcomes were assessed via logistic regression analysis to compare TURP outcomes from before and after the year 2001. Comparisons between variables were done...

Analysis of more than 400,000 women provides case-control evidence for BRCA1 and BRCA2 variant classification

Thu, 20 Nov 2025 00:00:00 +0000

Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS. As an initiative of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Analytical Working Group we analyze germline sequencing data of BRCA1 and BRCA2 from 96,691 female breast cancer cases and 302,116 controls from three studies: the BRIDGES study of the Breast Cancer Association Consortium, the Cancer Risk Estimates Related to Susceptibility consortium, and the UK Biobank. We observe 11,207 BRCA1 and BRCA2 variants, with 6909 being coding, covering 23.4% of BRCA1 and BRCA2 VUS in ClinVar and 19.2% of ClinVar curated (likely) benign or pathogenic variants. Case-control likelihood ratio (ccLR) evidence is highly consistent...

Assessing Recruitment Strategies for Creating an Inclusive Tenure Track Faculty in Health Sciences: A Cohort Study

Fri, 7 Nov 2025 00:00:00 +0000

Assessing Recruitment Strategies for Creating an Inclusive Tenure Track Faculty in Health Sciences: A Cohort Study

IFNγ enhances cytotoxic efficiency of the cytotoxic T lymphocytes against human glioma cells

Thu, 9 Oct 2025 00:00:00 +0000

Cytotoxic T lymphocytes (CTLs) are a key player in cancer immunotherapies, and MHC class I molecules on the cell surface are crucial for cellular recognition. However, the aberrant expression of MHC class I molecules is frequently found in various malignancies. IFNγ has dual functions in cancer progression, and its effect on tumor immunity is controversial. To investigate whether IFNγ can enhance cytotoxic efficiency of the tumor antigen-specific CTLs, we generated the CTLs using modified human dendritic cells as antigen presenting cells, then studied the activities of CTLs on human leukocyte antigen (HLA)-A2 positive glioma cells treated with, or without IFNγ. The results from both ELISpot and cytotoxicity assays demonstrated that the CTLs recognized and eliminated the HLA-A2 positive glioma cells treated with IFNγ more effectively when compared to the glioma cells deprived of IFNγ treatment. In addition, in vitro experiments showed that the levels of MHC class I molecules were...

Tumor growth inhibition by mSTEAP peptide nanovaccine inducing augmented CD8+ T cell immune responses

Thu, 9 Oct 2025 00:00:00 +0000

Poly(lactic-co-glycolic) acid (PLGA) has been successfully used in drug delivery and biomaterial applications, but very little attention has been directed towards the potential in vivo effects of peptide-loaded PLGA nanoparticles (NPs), specifically the potency of intravenous (IV) STEAP peptide-loaded PLGA-NP (nanovaccine) dosing and whether STEAP-specific CD8+ T cells directly play a key role in tumor inhibition. To address these concerns, syngeneic prostate cancer mouse models were established and treated with either mSTEAP peptide emulsified in incomplete Freund’s adjuvant (IFA) via subcutaneous (SC) injection or mSTEAP peptide nanovaccine containing the same amount of peptide via IV or SC injection. Meanwhile, mice were treated with either CD8b mAb followed by nanovaccine treatment, free mSTEAP peptide, or empty PLGA-NPs. Immune responses in these mice were examined using cytotoxicity assays at 14 days after treatment. Tumor size and survival in various treatment groups...

Black–White disparities across the colorectal cancer care continuum in the USA

Mon, 11 Aug 2025 00:00:00 +0000

Colorectal cancer (CRC) remains a substantial public health challenge globally and is the second leading cause of cancer-related death in the USA. Despite advances in screening and treatment, disparities in CRC outcomes persist, especially among Black individuals in the USA, who face higher CRC incidence and mortality and lower survival compared with White individuals. Inequities are largely attributed to social determinants of health (SDOH), such as access to health care, socioeconomic conditions and systemic inequities. In this Review, we examine Black–White disparities in CRC outcomes across the CRC care continuum in the USA, highlighting contributing modifiable (non-biological) and non-modifiable (biological) risk factors. We also discuss successful interventions that have reduced or eliminated disparities. Existing evidence suggests that Black–White differences in CRC screening participation, CRC incidence and CRC mortality can be resolved. Future efforts must emphasize...

The tumor-sentinel lymph node immuno-migratome reveals CCR7⁺ dendritic cells drive response to sequenced immunoradiotherapy

Fri, 1 Aug 2025 00:00:00 +0000

Surgical ablation or broad radiation of tumor-draining lymph nodes can eliminate the primary tumor response to immunotherapy, highlighting the crucial role of these nodes in mediating the primary tumor response. Here, we show that immunoradiotherapy efficacy is dependent on treatment sequence and migration of modulated dendritic cells from tumor to sentinel lymph nodes. Using a tamoxifen-inducible reporter paired with CITE-sequencing in a murine model of oral cancer, we comprehensively characterize tumor immune cellular migration through lymphatic channels to sentinel lymph nodes at single-cell resolution, revealing a unique immunologic niche defined by distinct cellular phenotypic and transcriptional profiles. Through a structured approach of sequential immunomodulatory radiotherapy and checkpoint inhibition, we show that sequenced, lymphatic-sparing, tumor-directed radiotherapy followed by PD-1 inhibition achieves complete and durable tumor responses. Mechanistically, this treatment...

ARRDC3 tyrosine phosphorylation functions as a switch to control c-Src versus WWP2 interactions and distinct scaffolding functions

Tue, 17 Jun 2025 00:00:00 +0000

Mammalian α-arrestins are members of the same arrestin family as the ubiquitously expressed and extensively studied β-arrestins. Arrestins share common structural elements, including the conserved N- and C-arrestin-fold domains, polar core, finger loop, and C-terminal tail, all of which mediate protein-protein interactions. In β-arrestins, these domains enable the control of G protein-coupled receptor (GPCR) signaling and scaffolding interactions with various signaling proteins including c-Src. By contrast, the repertoire of α-arrestin scaffolding partners and regulatory mechanisms that control their interactions are not well-understood. α-arrestins differ considerably from β-arrestins in the C-terminal region; β-arrestins contain clathrin adaptor β-adaptin-binding sites, whereas α-arrestins harbor PPxY motifs, demonstrated to interact with WW domains of E3 ubiquitin ligases such as WWP2. Here we report the identification of a novel phosphorylation site, tyrosine (Y) 394, embedded...

Evaluation of the psychometric properties of the Oral Health Behavior Social Support (OHBSS) Scales in English and Spanish for Mexican-origin young adults

Mon, 26 May 2025 00:00:00 +0000

BackgroundValid, reliable measures of psychosocial constructs are needed in oral health research. This study quantitatively evaluated the psychometric properties of nine new Oral Health Behavior Social Support (OHBSS) scales, which measured support for three oral health behaviors (brushing, flossing, dental care), queried for each of three sources (family, health providers, others/friends).MethodsYoung Mexican-origin adults in the southwestern United States-Mexico border region completed an online survey, in English or Spanish (N = 502). Survey items included: OHBSS scales, general social support scales, oral health behaviors, self-rated oral health status, dental anxiety, acculturation and socio-demographics. Subsample 1 participants also completed a dental exam (N = 41). Subsample 2 participants also completed a repeat OHBSS survey two-to-six weeks later (N = 56).Psychometric properties were tabulated, overall and by language preference (English or Spanish). Convergent and divergent...

Characterization of Wnt Signaling Pathway Aberrations in Metastatic Prostate Cancer.

Thu, 17 Apr 2025 00:00:00 +0000

Wnt (wingless-type) signaling pathway (WSP) alterations have been identified in patients with prostate cancer and are implicated in disease progression and hormonal resistance. In this study, we utilized a multi-institutional dataset to characterize molecular alterations in the canonical and noncanonical WSPs in prostate cancer. Patients with prostate cancer who underwent tissue-based genomic sequencing were investigated. Tumors with somatic activating mutations in CTNNB1 or RSPO2 or inactivating mutations in either APC or RNF43 were characterized as having aberrant canonical Wnt signaling (WSP-activated). Overall survival analyses were restricted to microsatellite-stable (MSS) tumors lacking RNF43 G659fs* mutations. We also investigated noncanonical WSP by evaluation of ROR1, ROR2, and WNT5 in WSP-activated versus WSP wild-type (WSP-WT) tumors. Of 4,138 prostate cancer samples, 3,684 were MSS. Among MSS tumors, 42.4% were from metastatic sites, of which 19.1% were WSP activated,...

Emerging role of immunogenic cell death in cancer immunotherapy

Fri, 11 Apr 2025 00:00:00 +0000

Cancer immunotherapy, such as immune checkpoint blockade (ICB), has emerged as a groundbreaking approach for effective cancer treatment. Despite its considerable potential, clinical studies have indicated that the current response rate to cancer immunotherapy is suboptimal, primarily attributed to low immunogenicity in certain types of malignant tumors. Immunogenic cell death (ICD) represents a form of regulated cell death (RCD) capable of enhancing tumor immunogenicity and activating tumor-specific innate and adaptive immune responses in immunocompetent hosts. Therefore, gaining a deeper understanding of ICD and its evolution is crucial for developing more effective cancer therapeutic strategies. This review focuses exclusively on both historical and recent discoveries related to ICD modes and their mechanistic insights, particularly within the context of cancer immunotherapy. Our recent findings are also highlighted, revealing a mode of ICD induction facilitated by atypical...

Genetic and Regulatory Mechanisms of Comorbidity of Anxiety, Depression and ADHD: A GWAS Meta-Meta-Analysis Through the Lens of a System Biological and Pharmacogenomic Perspective in 18.5 M Subjects

Fri, 11 Apr 2025 00:00:00 +0000

Background: In the United States, approximately 1 in 5 children experience comorbidities with mental illness, including depression and anxiety, which lead to poor general health outcomes. Adolescents with substance use disorders exhibit high rates of co-occurring mental illness, with over 60% meeting diagnostic criteria for another psychiatric condition in community-based treatment programs. Comorbidities are influenced by both genetic (DNA antecedents) and environmental (epigenetic) factors. Given the significant impact of psychiatric comorbidities on individuals' lives, this study aims to uncover common mechanisms through a Genome-Wide Association Study (GWAS) meta-meta-analysis. Methods: GWAS datasets were obtained for each comorbid phenotype, followed by a GWAS meta-meta-analysis using a significance threshold of p < 5E-8 to validate the rationale behind combining all GWAS phenotypes. The combined and refined dataset was subjected to bioinformatic analyses,...

Long-term treatment of metastatic adenoid cystic carcinoma with sequential brachytherapy and stereotactic body radiotherapy

Fri, 11 Apr 2025 00:00:00 +0000

Adenoid cystic carcinoma is a malignancy that is difficult to treat and often metastasizes to the lung. Systemic chemotherapies are not effective for this tumor type, thus local therapies are frequently used. Here, we report a case demonstrating the use of extensive ablative interventions in controlling the progression of metastatic adenoid cystic carcinoma. A patient with adenoid cystic carcinoma developed numerous metastases to his lungs and liver. Local ablative therapies including interstitial brachytherapy and SBRT were used to treat approximately 80 different metastases over the course of a decade. Over 850 brachytherapy seeds were implanted in this patient, and the tumor control and patient outcome were good. As of the most recent follow-up in March 2024, the patient has survived for approximately 12 years since his diagnosis of adenoid cystic carcinoma. To our knowledge, this case represents the most brachytherapy treatments reported in a single patient. It highlights...

Reprogramming of tumor-associated macrophages via NEDD4-mediated CSF1R degradation by targeting USP18

Fri, 11 Apr 2025 00:00:00 +0000

Tumor-associated myeloid cells modulate the tumor microenvironment and affect tumor progression. Type I interferon (IFN-I) has multiple effects on tumors and immune response, and ubiquitin-specific peptidase 18 (USP18) functions as a negative regulator of IFN-I signal transduction. This study aims to examine the function of IFN-I in myeloid cells during tumor progression. Here, we show that deletion of USP18 in myeloid cells suppresses tumor progression. Enhanced IFN-I signaling and blocked USP18 expression prompt downregulation of colony stimulating factor 1 receptor (CSF1R) and polarization of tumor-associated macrophages toward pro-inflammatory phenotypes. Further in vitro experiments reveal that downregulation of CSF1R is mediated by ubiquitin-proteasome degradation via E3 ligase neural precursor cell-expressed, developmentaly downregulated 4 (NEDD4) and the IFN-induced increase in ubiquitin E2 ubiquitin-conjugating enzyme H5. USP18 impairs ubiquitination and subsequent...

Black women's perspectives on bladder health: Social‐ecological and life course contexts

Wed, 9 Apr 2025 00:00:00 +0000

AIMS: This paper explores Black women's perspectives on bladder health using a social-ecological conceptual framework and life course perspective. METHODS: We conducted a directed content analysis of data from the Study of Habits, Attitudes, Realities, and Experiences (SHARE), a focus group study by the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium. Analysis was conducted on data from five focus groups and a member-checking session where all participants self-identified as Black or African American. RESULTS: Forty-two participants aged 11-14 or 45+ years reported life course experiences with their bladder. The intersection of race and gender was the lens through which participants viewed bladder health. Participants' accounts of their perspectives on bladder health explicitly and implicitly revealed structural racism as an explanatory overarching theme. Participants described (a) historically-rooted and still pervasive practices of discrimination and segregation,...

Risk of Esophageal Cancer in Achalasia: A Matched Cohort Study Using the Nationwide Veterans Affairs Achalasia Cohort

Tue, 8 Apr 2025 00:00:00 +0000

INTRODUCTION: Achalasia is a postulated risk factor of esophageal cancer (EC); however, EC-associated risk in achalasia is understudied. We aimed to evaluate EC risk among individuals within the nationwide Veterans Affairs Achalasia Cohort. METHODS: We conducted a matched cohort study among US veterans aged 18 years or older from 1999 to 2019. Individuals with achalasia were age matched and sex matched 1:4 to individuals without achalasia. Follow-up continued from study entry until diagnosis with incident/fatal EC (primary outcome), death from non-EC-related causes, or end of the study follow-up (December 31, 2019). Association between achalasia and EC risk was examined using Cox regression models. RESULTS: We included 9,315 individuals in the analytic cohort (median age 55 years; 92% male): 1,863 with achalasia matched to 7,452 without achalasia. During a median 5.5 years of follow-up, 17 EC occurred (3 esophageal adenocarcinoma, 12 squamous cell carcinoma, and 2 unknown type)...

Effects of Androgen Deprivation Therapy on Prostate Cancer Outcomes According to Competing Event Risk: Secondary Analysis of a Phase 3 Randomised Trial

Mon, 7 Apr 2025 00:00:00 +0000

BACKGROUND: Previous studies indicate that the benefit of short-term androgen deprivation therapy (ADT) with radiotherapy (RT) for prostate cancer depends on competing risks. OBJECTIVE: To determine whether a quantitative method to stratify patients by risk for competing events (omega score) could identify subgroups that selectively benefit from ADT. DESIGN, SETTING, AND PARTICIPANTS: An ancillary analysis of NRG/RTOG 9408 phase 3 trial (NCT00002597) involving 1945 prostate cancer patients was conducted. INTERVENTION: Short-term ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We applied generalised competing event regression models incorporating age, performance status, comorbidity, T category, Gleason score (GS), and prostate-specific antigen (PSA), to stratify patients according to relative hazards for primary cancer-related events (distant metastasis or prostate cancer death) versus competing noncancer mortality. We tested interactions between ADT and subgroups defined...

Development of new bilingual oral health behavior social support (OHBSS) scales in English and Spanish

Thu, 3 Apr 2025 00:00:00 +0000

This paper describes the simultaneous co-development of Oral Health Behavior Social Support (OHBSS) scales in English and Spanish. OHBSS scales assess social support for toothbrushing, flossing, and dental care utilization, which are targets for interpersonal-level interventions to promote oral health among Hispanic/Latino adults. The focus was on Mexican-origin adults, who comprise the largest United States Hispanic/Latino subgroup and experience a high oral disease burden. All participants self-identified as Mexican-origin adults (ages 21-40 years old), living along the California-Arizona-Mexico border. Independent samples were recruited for each study partnering with Federally Qualified Health Centers. First, we conducted semi-structured interviews about social support for oral health behaviors in August to November 2018 (Study 1, N = 72). Interviews were audio recorded, transcribed (in original language, Spanish or English), and qualitative data were coded and analyzed in...

Endosomal actin branching, fission, and receptor recycling require FCHSD2 recruitment by MICAL-L1

Wed, 2 Apr 2025 00:00:00 +0000

Endosome fission is required for the release of carrier vesicles and the recycling of receptors to the plasma membrane. Early events in endosome budding and fission rely on actin branching to constrict the endosomal membrane, ultimately leading to nucleotide hydrolysis and enzymatic fission. However, our current understanding of this process is limited, particularly regarding the coordination between the early and late steps of endosomal fission. Here we have identified a novel interaction between the endosomal scaffolding protein, MICAL-L1, and the human homologue of the Drosophila Nervous Wreck (Nwk) protein, FCH and double SH3 domains protein 2 (FCHSD2). We demonstrate that MICAL-L1 recruits FCHSD2 to the endosomal membrane, where it is required for ARP2/3-mediated generation of branched actin, endosome fission and receptor recycling to the plasma membrane. Because MICAL-L1 first recruits FCHSD2 to the endosomal membrane, and is subsequently responsible for recruitment...

A Mixed Methods Comparison of Oral Hygiene Behaviors by Gender Among Mexican-Origin Young Adults in California

Thu, 27 Mar 2025 00:00:00 +0000

Objective: This mixed methods study explores gender differences in, and reasons for, toothbrushing and flossing among Mexican-origin adults. Methods: Interviews and surveys about oral hygiene behaviors were collected from 72 adults (ages 21-40) living on the California-Mexico border. Interviews were audio-recorded, transcribed in their original language (English/Spanish), then coded. Survey responses were linked to coded transcripts in Dedoose. Qualitative reports were thematically analyzed for each behavior, stratified into four groups by gender and whether or not participants met American Dental Association (ADA) weekly guidelines (brushing ≥ 14/week; flossing ≥ 7/week). Self-reported weekly frequencies of brushing and flossing were collected continuously, and then dichotomized as meeting guidelines or not. Kruskal-Wallis and chi-square tests assessed differences in hygiene behavior frequency by gender. Negative binomial and logistic regressions were performed, accounting for...

Cardiovascular events after cancer immunotherapy as oncologic emergencies: Analyses of 610 head and neck cancer patients treated with immune checkpoint inhibitors

Wed, 19 Mar 2025 00:00:00 +0000

BACKGROUND: Cardio-oncology and emergency medicine are closely collaborative, as many cardiac events in cancer patients require evaluation and treatment in the emergency department (ED). Immune checkpoint inhibitors (ICIs) have become a common treatment for patients with head and neck cancer (HNC). However, the immune-related adverse events (irAEs) from ICIs can be clinically significant. METHODS: We reviewed and analyzed cardiovascular diagnoses among HNC patients who received ICI during the period April 1, 2016-December 31, 2020 in a large tertiary cancer center. Demographics, clinical and cancer-related data were abstracted, and billing databases were queried for cardiovascular disease (CVD)-related diagnosis using International Classification of Disease-version10 (ICD-10) codes. We recorded receipt of care at the ED as one of the outcome variables. RESULTS: A total of 610 HNC patients with a median follow-up time of 12.3 months (median, interquartile range = 5-30 months) comprised...

Birth Cohort Colorectal Cancer (CRC): Implications for Research and Practice

Tue, 18 Mar 2025 00:00:00 +0000

Colorectal cancer (CRC) epidemiology is changing due to a birth cohort effect, first recognized by increasing incidence of early onset CRC (EOCRC, age <50 years). In this paper, we define "birth cohort CRC" as the observed phenomenon, among individuals born 1960 and later, of increasing CRC risk across successive birth cohorts, rising EOCRC incidence, increasing incidence among individuals aged 50 to 54 years, and flattening of prior decreasing incidence among individuals aged 55 to 74 years. We demonstrate birth cohort CRC is associated with unique features, including increasing rectal cancer (greater than colon) and distant (greater than local) stage CRC diagnosis, and increasing EOCRC across all racial/ethnic groups. We review potential risk factors, etiologies, and mechanisms for birth cohort CRC, using EOCRC as a starting point and describing importance of viewing these through the lens of birth cohort. We also outline implications of birth cohort CRC for epidemiologic...

Mental health and social connection among older lesbian and bisexual women

Tue, 18 Mar 2025 00:00:00 +0000

OBJECTIVE: To assess differences in psychosocial and mental health outcomes between older lesbian and bisexual women compared to heterosexual women. DESIGN: Cross sectional study. SETTING: The study was carried out in the California Teachers Study, a prospective cohort study. PARTICIPANTS: Self-identified heterosexual (n = 35,846), lesbian (n = 710), and bisexual (n = 253) women 50 years of age and older were enrolled. MEASUREMENTS: Validated questionnaires were used to measure social connection, overall happiness, and depression. Logistic regression modeling was used to estimate odds ratios (OR) and 95% confidence intervals (CI) comparing lesbian and bisexual women separately to heterosexual women in relation to psychosocial and mental health outcomes. RESULTS: After controlling for age and marital status, older bisexual women were significantly more likely to report lack of companionship (OR = 2.00; 95% CI, 1.30-3.12) and feeling left out (OR = 2.33; 95%...

Correction: Roy et al. Metformin and ICG-001 Act Synergistically to Abrogate Cancer Stem Cells-Mediated Chemoresistance in Colorectal Cancer by Promoting Apoptosis and Autophagy. Cancers 2022, 14, 1281

Sat, 1 Mar 2025 00:00:00 +0000

In the original publication [...].

Characteristics and Outcomes of T1a Renal Cell Carcinoma Presenting with Metastasis

Sat, 1 Mar 2025 00:00:00 +0000

OBJECTIVES: The incidence of renal cell carcinoma (RCC) has been rising, largely due to increased incidental detection from widespread imaging. Although synchronous distant metastasis (SM) with a primary renal tumor measuring <4 cm (cT1a) is uncommon, its presence may influence survival outcomes and the utility of cytoreductive nephrectomy. We sought to investigate clinical characteristics, metastatic patterns, treatments, and survival outcomes of patients with T1a RCC. METHODS: All patients aged ≥18 years diagnosed with RCC between 2004 and 2019 were extracted from the National Cancer Database. The Cochran-Armitage test was used for trend analysis, while multivariable analyses were conducted to identify variables associated with SM and to assess the impact of cytoreductive surgery on mortality across isolated metastatic sites. Kaplan-Meier analysis was performed to compare survival outcomes. RESULTS: A total of 263,911 individuals diagnosed with T1a RCC were analyzed in the...

Guided Self-Help vs. Group Treatment for Children with Obesity: A Randomized Clinical Trial

Fri, 28 Feb 2025 00:00:00 +0000

BACKGROUND AND OBJECTIVES: Family-based behavioral treatment (FBT) for children with obesity is provided in weekly parent and child groups over 6 months. A guided self-help FBT program (gshFBT) is provided to the dyad in short meetings. Both interventions provide the same content; however, gshFBT provides this content in less time (FBT = 23 hours, gshFBT = 5.3 hours). This study aimed to evaluate whether gshFBT is noninferior to FBT on child weight loss and cost-effectiveness. METHODS: 150 children aged between 7.0 and 12.9 years with a BMI between the 85th and 99.9th percentile and their parent were recruited and randomized to a 6-month program of gshFBT (n = 75) or FBT (n = 75) and were followed 12 months post-treatment. RESULTS: A total of 150 children (mean age = 10.1 years, 49% female, mean BMIz = 2.09) and their parent (mean age = 41.5 years, 87% female, 45% Hispanic, 37% White non-Hispanic, 9.7% Asian, 4.8% Black, 7.3% other) were recruited...

Multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology

Fri, 28 Feb 2025 00:00:00 +0000

Abstract Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we exploit the distributed nature of genetic effects across the brain and apply the Multivariate Omnibus Statistical Test (MOSTest) to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) cortical measures from N=35,657 participants in the UK Biobank. We identified 695 loci for cortical surface area and 539 for cortical thickness, in total 780 unique genetic loci associated with cortical morphology. This reflects an approximate 10-fold increase compared to the commonly applied univariate GWAS methods. Power analysis indicates that applying MOSTest to vertex-wise structural MRI data triples the effective sample size compared to conventional univariate GWAS approaches. Functional follow up including gene-based analyses implicate 10% of all protein-coding genes and point...

Advanced Restriction imaging and reconstruction Technology for Prostate MRI (ART-Pro): Study protocol for a multicenter, multinational trial evaluating biparametric MRI and advanced, quantitative diffusion MRI for detection of prostate cancer

Fri, 14 Feb 2025 00:00:00 +0000

Abstract: Background: Multiparametric MRI (mpMRI) is strongly recommended by current clinical guidelines for improved detection of clinically significant prostate cancer (csPCa). However, major limitations of mpMRI are the need for intravenous (IV) contrast and dependence on reader expertise. Efforts to address these issues include use of biparametric MRI (bpMRI) and advanced, quantitative MRI techniques. One such advanced technique is the Restriction Spectrum Imaging restriction score (RSIrs), an imaging biomarker that has been shown to improve quantitative accuracy of patient-level csPCa detection. Purpose: To evaluate whether IV contrast can be avoided in the setting of standardized, state-of-the-art image acquisition, with or without addition of RSIrs, and to evaluate characteristics of RSIrs as a stand-alone, quantitative biomarker. Design, setting, and participants: ART-Pro is a multisite, multinational trial that will be conducted in two stages, evaluating bpMRI,...

Discrimination Between Benign and Malignant Lesions With Restriction Spectrum Imaging MRI in an Enriched Breast Cancer Screening Cohort

Fri, 14 Feb 2025 00:00:00 +0000

BACKGROUND: Breast cancer screening with dynamic contrast-enhanced MRI (DCE-MRI) is recommended for high-risk women but has limitations, including variable specificity and difficulty in distinguishing cancerous (CL) and high-risk benign lesions (HRBL) from average-risk benign lesions (ARBL). Complementary non-invasive imaging techniques would be useful to improve specificity. PURPOSE: To evaluate the performance of a previously-developed breast-specific diffusion-weighted MRI (DW-MRI) model (BS-RSI3C) to improve discrimination between CL, HRBL, and ARBL in an enriched screening population. STUDY TYPE: Prospective. SUBJECTS: Exactly 187 women, either with mammography screening recommending additional imaging (N = 49) or high-risk individuals undergoing routine breast MRI (N = 138), before the biopsy. FIELD STRENGTH/SEQUENCE: Multishell DW-MRI echo planar imaging sequence with a reduced field of view at 3.0 T. ASSESSMENT: A total of 72 women had at least one biopsied lesion, with...

Restriction Spectrum Imaging as a quantitative biomarker for prostate cancer with reliable positive predictive value

Fri, 14 Feb 2025 00:00:00 +0000

Abstract Background and Objective Positive predictive value of PI-RADS for clinically significant prostate cancer (csPCa, grade group [GG]≥2) varies widely between institutions and radiologists. The Restriction Spectrum Imaging restriction score (RSIrs) is a metric derived from diffusion MRI that could be an objectively interpretable biomarker for csPCa. Methods In patients scanned for suspected or known csPCa at 7 centers, we calculated patient-level csPCa probability based on maximum RSIrs in the prostate, without relying on subjectively defined lesions. We used area under the ROC curve (AUC) to compare patient-level csPCa detection for RSIrs, ADC, and PI-RADS. Finally, we combined RSIrs with clinical risk factors via multivariable regression, training in a single-center cohort and testing in an independent, multi-center dataset. Key Findings and Limitations Among all patients (n=1892), probability of csPCa increased with higher RSIrs . GG≥4 csPCa was most common in patients...

Robustness of a Restriction Spectrum Imaging (RSI) quantitative MRI biomarker for prostate cancer: assessing for systematic bias due to age, race, ethnicity, prostate volume, medication use, or imaging acquisition parameters

Fri, 14 Feb 2025 00:00:00 +0000

Introduction Prostate multiparametric magnetic resonance imaging (mpMRI) has greatly improved the detection of clinically significant prostate cancer (csPCa). However, the limited number of expert sub-specialist radiologists capable of interpreting conventional prostate mpMRI is a bottleneck for universal access to this healthcare advance. A reliable and reproducible quantitative imaging biomarker could facilitate implementation of accurate prostate MRI at clinical sites with limited experience, thus ensuring more equitable patient care. Restriction Spectrum Imaging restriction score (RSIrs) is an MRI biomarker that has shown the ability to enhance the qualitative and quantitative interpretation of prostate MRI. However, patient-level factors (age, race, ethnicity, prostate volume, and 5-alpha-reductase inhibitor (5-ARI) use) and acquisition-level factors (scanner manufacturer/model and protocol parameters) can affect prostate mpMRI, and their impact on quantitative RSIrs is unknown....

From a genomic risk model to clinical trial implementation in a learning health system: the ProGRESS Study

Thu, 13 Feb 2025 00:00:00 +0000

ABSTRACT: Background: As healthcare moves from a one-size-fits-all approach towards precision care, individual risk prediction is an important step in disease prevention and early detection. Biobank-linked healthcare systems can generate knowledge about genomic risk and test the impact of implementing that knowledge in care. Risk-stratified prostate cancer screening is one clinical application that might benefit from such an approach. Methods: We developed a clinical translation pipeline for genomics-informed prostate cancer screening in a national healthcare system. We used data from 585,418 male participants of the Veterans Affairs (VA) Million Veteran Program (MVP), among whom 101,920 self-identify as Black/African-American, to develop and validate the Prostate CAncer integrated Risk Evaluation (P-CARE) model, a prostate cancer risk prediction model based on a polygenic score, family history, and genetic principal components. The model was externally validated in data from...

Barriers and facilitators to telemedicine contraception among patients that speak Spanish: a qualitative study

Thu, 13 Feb 2025 00:00:00 +0000

Background: Telemedicine contraception services have increased since the COVID-19 pandemic. There may be unique equity implications and language barriers for patients who speak Spanish. Objective: To identify the barriers and facilitators of telemedicine for contraception care among patients who speak Spanish using a community-based participatory research approach. Study Design: The study was designed and conducted in consultation with a community advisory board. We interviewed 20 patients after telemedicine and in-person contraception visits conducted in Spanish at Planned Parenthood of the Pacific Southwest in Southern California between April 2022 and May 2023. Telemedicine visits were conducted by audio only. Two coders analyzed the data using thematic analysis. Results: The average age of the participants was 32.5 years old (range 19-45). Most participants had some college education (13/20, 65.0%) and public insurance (18/20, 90.0%). Most chose a short-acting contraceptive...

Clinical Impact of Contouring Variability for Prostate Cancer Tumor Boost

Thu, 13 Feb 2025 00:00:00 +0000

PURPOSE: The focal radiation therapy (RT) boost technique was shown in a phase III randomized controlled trial (RCT) to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. A recent prospective study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists' contour inaccuracies would yield meaningfully worse clinical outcomes. METHODS AND MATERIALS: Forty-five radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the RCT protocol. The...

Deep learning AI and Restriction Spectrum Imaging for patient-level detection of clinically significant prostate cancer on MRI

Thu, 13 Feb 2025 00:00:00 +0000

Abstract Background The Prostate Imaging Reporting & Data System (PI-RADS), based on multiparametric MRI (mpMRI), is widely used for the detection of clinically significant prostate cancer (csPCa, Gleason Grade Group (GG≥2)). However, its diagnostic accuracy can be impacted by variability in interpretation. Restriction Spectrum Imaging (RSI), an advanced diffusion-weighted technique, offers a standardized, quantitative approach for detecting csPCa, potentially enhancing diagnostic consistency and performing comparably to expert-level assessments. Purpose To evaluate whether combining maximum RSI-derived restriction scores (RSIrs-max) with deep learning (DL) models can enhance patient-level detection of csPCa compared to using PI-RADS or RSIrs-max alone. Materials and Methods Data from 1,892 patients across seven institutions were analyzed, selected based on MRI results and biopsy-confirmed diagnoses. Two deep learning architectures, 3D-DenseNet and 3D-DenseNet+RSI (incorporating...

Pancreatic cyst features predict future development of pancreatic cancer: results of a nested case-control study

Tue, 11 Feb 2025 00:00:00 +0000

BACKGROUND AND AIMS: Risk factors for pancreatic cancer among patients with pancreatic cysts are incompletely characterized. The primary aim of this study was to evaluate risk factors for development of pancreatic cancer among patients with pancreatic cysts. METHODS: We conducted a retrospective case-control study of U.S. veterans with a suspected diagnosis of branch-duct intraductal papillary mucinous neoplasm from 1999 to 2013. RESULTS: Age (hazard ratio [HR], 1.03 per year; 95% confidence interval [CI], 1.00-1.06), larger cyst size at cyst diagnosis (HR, 1.03 per mm; 95% CI, 1.01-1.04), cyst growth rate (HR, 1.22 per mm/y; 95% CI, 1.14-1.31), and pancreatic duct dilation (5-9.9 mm: HR, 3.78; 95% CI, 1.90-7.51; ≥10 mm: HR, 13.57; 95% CI, 5.49-33.53) were found to be significant predictors for pancreatic cancer on multivariable analysis. CONCLUSIONS: Age, cyst size, cyst growth rate, and high-risk or worrisome features were associated with a higher...

Advanced Restriction Imaging and Reconstruction Technology for Prostate Magnetic Resonance Imaging (ART-Pro): A Study Protocol for a Multicenter, Multinational Trial Evaluating Biparametric Magnetic Resonance Imaging and Advanced, Quantitative Diffusion Magnetic Resonance Imaging for the Detection of Prostate Cancer

Fri, 31 Jan 2025 00:00:00 +0000

Multiparametric magnetic resonance imaging (mpMRI) is strongly recommended by current clinical guidelines for improved detection of clinically significant prostate cancer (csPCa). However, the major limitations are the need for intravenous (IV) contrast and dependence on reader expertise. Efforts to address these issues include use of biparametric magnetic resonance imaging (bpMRI) and advanced, quantitative magnetic resonance imaging (MRI) techniques. One such advanced technique is the Restriction Spectrum Imaging restriction score (RSIrs), an imaging biomarker that has been shown to improve quantitative accuracy of patient-level csPCa detection. Advanced Restriction imaging and reconstruction Technology for Prostate MRI (ART-Pro) is a multisite, multinational trial that aims to evaluate whether IV contrast can be avoided in the setting of standardized, state-of-the-art image acquisition, with or without addition of RSIrs. Additionally, RSIrs will be evaluated as a stand-alone,...

Personal legacy and treatment choices for serious illness: a scoping review

Fri, 31 Jan 2025 00:00:00 +0000

BACKGROUND: Legacy-how one hopes to be remembered after death-is an unexplored and important dimension of decision-making for people facing serious illness. OBJECTIVES: We conducted a scoping review to answer the following research questions: (1) How do people making treatment choices conceive of legacy? and (2) What treatment choices do people make with legacy in mind? ELIGIBILITY CRITERIA: Participants included people facing serious illness who discussed how they wanted to be remembered after their own death, or how they hoped to impact others, as they made treatment choices. Studies in English published between 1990 and 2022 were included. SOURCES OF EVIDENCE: We conducted searches in electronic databases including Medline/PubMed, CINAHL, PsycInfo, SocialWork, AnthropologyPlus, Web of Science, ProQuest and EMBASE databases. DATA SYNTHESIS: We used an electronic screening tool to screen abstracts and review full-text articles suitable for inclusion. We analysed included articles...

Review article: Lynch Syndrome—a mechanistic and clinical management update

Tue, 28 Jan 2025 00:00:00 +0000

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant familial condition caused by a pathogenic variant (PV) in a DNA mismatch repair gene, which then predisposes carriers to various cancers. AIM: To review the pathogenesis, clinical presentation, differential diagnosis and clinical strategies for detection and management of LS. METHODS: A narrative review synthesising knowledge from published literature, as well as current National Comprehensive Cancer Network guidelines for management of LS was conducted. RESULTS: LS tumours are characterised by unique pathogenesis, ultimately resulting in hypermutation, microsatellite instability and high immunogenicity that has significant implications for cancer risk, clinical presentation, treatment and surveillance. LS is one of the most common hereditary causes of cancer, and about 1 in 279 individuals carry a PV in an LS gene that predisposes to associated cancers. Individuals with LS have increased risks for colorectal, endometrial...

Screening for Colorectal Cancer: The Role of Clinical Laboratories

Sun, 19 Jan 2025 00:00:00 +0000

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer incidence and mortality. Screening can result in reductions in incidence and mortality, but there are many challenges to uptake and follow-up. CONTENT: Here, we will review the changing epidemiology of CRC, including increasing trends for early and later onset CRC; evidence to support current and emerging screening strategies, including noninvasive stool and blood-based tests; key challenges to ensuring uptake and high-quality screening; and the critical role that clinical laboratories can have in supporting health system and public health efforts to reduce the burden of CRC on the population. SUMMARY: Clinical laboratories have the opportunity to play a seminal role in optimizing early detection and prevention of CRC.

Dopamine Dysregulation in Reward and Autism Spectrum Disorder.

Fri, 17 Jan 2025 00:00:00 +0000

Autism spectrum disorder (ASD) is primarily characterized by core deficits in social skills, communication, and cognition and by repetitive stereotyped behaviors. These manifestations are variable between individuals, and ASD pathogenesis is complex, with over a thousand implicated genes, many epigenetic factors, and multiple environmental influences. The mesolimbic dopamine (DA) mediated brain reward system is held to play a key role, but the rapidly expanding literature reveals intricate, nuanced signaling involving a wide array of mesolimbic loci, neurotransmitters and receptor subtypes, and neuronal variants. How altered DA signaling may constitute a downstream convergence of the manifold causal origins of ASD is not well understood. A clear working framework of ASD pathogenesis may help delineate common stages and potential diagnostic and interventional opportunities. Hence, we summarize the known natural history of ASD in the context of emerging data and perspectives to...

Pilot Study of Personalized Transcranial Magnetic Stimulation with Spectral Electroencephalogram Analyses for Assessing and Treating Persons with Autism.

Fri, 17 Jan 2025 00:00:00 +0000

Autism spectrum condition (ASC) is a neurodevelopmental condition that is only partly responsive to prevailing interventions. ASC manifests core challenges in social skills, communication, and sensory function and by repetitive stereotyped behaviors, along with imbalances in the brains excitatory (E) and inhibitory (I) signaling. Repetitive transcranial magnetic stimulation (rTMS) has shown promise in ASC and may be a useful addition to applied behavioral analysis (ABA), a gold-standard psychotherapeutic intervention. We report an open-label clinical pilot (initial) study in which ABA-treated ASC persons (n = 123) received our personalized rTMS protocol (PrTMS). PrTMS uses low TMS pulse intensities and continuously updates multiple cortical stimulation locales and stimulation frequencies based on the spectral EEG and psychometrics. No adverse effects developed, and 44% of subjects had ASC scale scores reduced to below diagnostic cutoffs. Importantly, in PrTMS responders, the spectral...

Personalized repetitive transcranial magnetic stimulation (prtms®) for post-traumatic stress disorder (ptsd) in military combat veterans

Fri, 17 Jan 2025 00:00:00 +0000

Emerging data suggest that post-traumatic stress disorder (PTSD) arises from disrupted brain default mode network (DMN) activity manifested by dysregulated encephalogram (EEG) alpha oscillations. Hence, we pursued the treatment of combat veterans with PTSD (n = 185) using an expanded form of repetitive transcranial magnetic stimulation (rTMS) termed personalized-rTMS (PrTMS). In this treatment methodology spectral EEG based guidance is used to iteratively optimize symptom resolution via (1) stimulation of multiple motor sensory and frontal cortical sites at reduced power, and (2) adjustments of cortical treatment loci and stimulus frequency during treatment progression based on a proprietary frequency algorithm (PeakLogic, Inc. San Diego) identifying stimulation frequency in the DMN elements of the alpha oscillatory band. Following 4 - 6 weeks of PrTMS® therapy in addition to routine PTSD therapy, veterans exhibited significant clinical improvement accompanied by increased...

N107C/CEC.3 (ALLIANCE FOR CLINICAL TRIALS IN ONCOLOGY/CANADIAN CANCER TRIALS GROUP): PHASE III TRIAL OF POST-OPERATIVE RADIOSURGERY COMPARED WITH WHOLE BRAIN RADIOTHERAPY FOR RESECTED METASTATIC BRAIN DISEASE: COGNITIVE FUNCTION OF LONG-TERM SURVIVORS

Thu, 16 Jan 2025 00:00:00 +0000

N107C/CEC.3 (ALLIANCE FOR CLINICAL TRIALS IN ONCOLOGY/CANADIAN CANCER TRIALS GROUP): PHASE III TRIAL OF POST-OPERATIVE RADIOSURGERY COMPARED WITH WHOLE BRAIN RADIOTHERAPY FOR RESECTED METASTATIC BRAIN DISEASE: COGNITIVE FUNCTION OF LONG-TERM SURVIVORS

A randomized phase II trial of atezolizumab with or without tiragolumab before and after definitive chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC; AFT-57)

Thu, 16 Jan 2025 00:00:00 +0000

A randomized phase II trial of atezolizumab with or without tiragolumab before and after definitive chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC; AFT-57)

Transoral Surgery in HPV‐Positive Oropharyngeal Carcinoma: Oncologic Outcomes in the Veterans Affairs System

Mon, 13 Jan 2025 00:00:00 +0000

OBJECTIVES: Most transoral robotic surgery (TORS) literature for HPV-positive oropharyngeal squamous cell carcinoma (HPV-OPC) derives from high-volume tertiary-care centers. This study aims to describe long-term recurrence and survival outcomes among Veterans Health Administration patients. MATERIALS AND METHODS: Using the US Veterans Affairs database, we identified patients with HPV-OPC treated with TORS between January 2010 and December 2016. Patients were stratified in risk categories: low (0-1 metastatic nodes, negative margins), intermediate (close margins, 2-4 metastatic nodes, lymphovascular or perineural invasion, pT3-pT4 tumor), or high (positive margins, extranodal extension (ENE), and/or ≥5 metastatic nodes). Primary outcomes included overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). RESULTS: The cohort included 161 patients of which 29 (18%) were low-risk, 45 (28%) intermediate-risk, and 87 (54%) high-risk. ENE was present...

Tumor-Targeted Cell-Penetrating Peptides Reveal That Monomethyl Auristatin E Temporally Modulates the Tumor Immune Microenvironment

Sat, 4 Jan 2025 00:00:00 +0000

Chemotherapies remain standard therapy for cancers but have limited efficacy and cause significant side effects, highlighting the need for targeted approaches. In the progression of cancer, tumors increase matrix metalloproteinase (MMP) activity. Leveraging and therapeutically redirecting tumor MMPs through activatable cell-penetrating peptide (ACPP) technology offers new approaches for tumor-selective drug delivery and for studying how drug payloads engage the tumor immune microenvironment. ACPPs are biosensing peptides consisting of a drug-conjugated polycationic cell-penetrating peptide masked by an autoinhibitory polyanionic peptide through an interlinking peptide linker. Since tumors overexpress MMPs, ACPP tumor-targeting is achieved using an MMP cleavable linker. Monomethyl auristatin E (MMAE) is a potent anti-tubulin and common drug payload in antibody drug conjugates; however there are limited pre-clinical studies on how this clinically effective drug modulates the interplay...

Social risk factors and cancer prevention care among patients in community health-care settings

Sat, 28 Dec 2024 00:00:00 +0000

BACKGROUND: Social risks are negatively associated with receipt of cancer preventive care. As knowledge is lacking on the pathways underlying these associations, we investigated associations between patient-reported social risks and colorectal cancer (CRC), cervical cancer, and breast cancer screening order provision and screening completion. METHODS: This study included patients eligible for CRC, cervical cancer, or breast cancer screening at 186 community-based clinics between July 1, 2015, and February 29, 2020. Outcomes included up-to-date status for indicated cancer screenings at baseline; percentage of subsequent study months in which patients were up-to-date on screenings; screening order receipt; and screening completion. Independent variables were patient-reported food insecurity, transportation barriers, and housing instability. Analyses used covariate-adjusted generalized estimating equation models, stratified by social risk. RESULTS: Patients with documented social...

Epidemiology of Gastric Malignancies 2000–2018 According to Histology: A Population-Based Analysis of Incidence and Temporal Trends

Wed, 11 Dec 2024 00:00:00 +0000

BACKGROUND & AIMS: Gastric cancer (GC) remains a leading cause of cancer and cancer-related mortality. Recent reports suggest noncardia GC is increasing in certain U.S. POPULATIONS: However, whether these trends are driven by gastric adenocarcinoma (GA) or other histologies, including neuroendocrine tumors (NETs), lymphoma, or gastrointestinal stromal tumors (GISTs), is unclear. METHODS: We analyzed the Surveillance, Epidemiology and End Results-18 cancer registry (2000-2018) to determine age-standardized incidence rates (ASIR) and annual percentage change (APC) trends for histologically-confirmed GCs, stratified by anatomic location (noncardia vs cardia), age group (20-49 vs 50+ years), sex, race, and ethnicity. Joinpoint regression modeling estimated the statistical significance of trend comparisons. RESULTS: Of 74,520 individuals with noncardia GC, most (66.2%) were GA, with the next largest categories being non-mucosa-associated lymphoid tissue (non-MALT) lymphomas (6.9%),...

INTRACOLON COOLING INCREASES SURVIVAL RATE IN THE RAT MODEL OF LETHAL HEMORRHAGE

Tue, 10 Dec 2024 00:00:00 +0000

ABSTRACT: Background: The objective of this study was to investigate whether transrectal intracolon (TRIC) cooling can prolong the survival duration in a rat hemorrhagic shock (HS) model. Methods: A lethal HS was induced by bleeding 47% of the total blood volume. A TRIC device was placed into the colon to maintain the intracolon temperature either at 37°C (TRIC37) or at 10°C (TRIC10) post-HS. In the surface cooling (SC) rats, the body temperatures were maintained at the same level as the esophageal temperature of the TRIC10 rats. A separated group of TRIC10 rats were resuscitated (Res) at 90 min post-HS. A total of six groups were as follows: (i) Sham TRIC37 (n = 5), (ii) Sham TRIC10 (n = 5), (iii) HS TRIC37 (n = 5), (iv) HS TRIC10 (n = 6), (v) HS SC (n = 6), and (vi) HS TRIC10 + Res (n = 6). Results: An average post-HS survival time was 18.4 ± 9.4 min in HS TRIC37 and 82 ± 27.82 min in the HS SC group. In striking contrast, the HS TRIC10 group exhibited an average survival time...

Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial

Fri, 6 Dec 2024 00:00:00 +0000

PURPOSE: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups...

Examining the Association of Social Needs with Future Health Care Utilization in an Older Adult Population: Which Needs Are Most Important?

Fri, 6 Dec 2024 00:00:00 +0000

Abstract Social needs, such as social isolation and food insecurity, are important individual-level social determinants of health, especially for adults ages 65 years and older. These needs may be associated with future health care utilization, but this research area has not been studied extensively. The objective of this study was to examine the independent association of 5 individual social needs with future (1) emergency department (ED) visits and (2) hospital admissions. This observational study included 9649 Kaiser Permanente Northwest (KPNW) Medicare members who completed the Medicare Total Health Assessment (MTHA) quality improvement survey between August 17, 2020 and January 31, 2022. The 5 social needs assessed by the MTHA, defined as binary measures (yes/no), included (1) financial strain, (2) food insecurity, (3) housing instability, (4) social isolation, and (5) transportation needs. ED utilization (yes/no) and hospitalization (yes/no), the current study...

Molecular and clinical correlates of high PSMA/FOLH1 mRNA expression in primary and metastatic prostate cancer (PC).

Thu, 5 Dec 2024 00:00:00 +0000

5051 Background: The FOLH1 gene encodes prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein that is expressed in PC cells. PSMA is a target for diagnostic imaging and treatment in PC. We utilized a database of molecularly profiled PC tumors to evaluate correlates of high FOLH1 mRNA expression. Methods: NextGen sequencing of DNA (592-gene/whole exome) and RNA (whole transcriptome) was performed on PC specimens (n=7,558) through Caris Life Sciences. FOLH1-High/Low expression was defined as above/below median RNA transcripts per million (TPM). Androgen receptor (AR), neuroendocrine (NEPC), MAPK, and T-cell inflamed RNA signature scores were calculated. Tumor cell PD-L1+ expression (≥2+, ≥5%; SP142) was assessed by IHC. Overall survival (OS) and time on treatment (TOT) were calculated from time of diagnosis or therapy start. Results: Specimens were derived from the prostate gland (n=4495, 59.5%), lymph nodes (n=858, 11.4%), bone (n=568, 7.5%), liver (n=359,...

Disparate outcomes among Latino and non-Hispanic White (NHW) patients with metastatic clear cell renal cell carcinoma (mccRCC).

Thu, 5 Dec 2024 00:00:00 +0000

4554 Background: Some studies have demonstrated that Latino patients (pts) with mccRCC have worse clinical outcomes than NHW pts. It is unclear if this disparity is related to biological differences and/or social determinants of health (SDOH). Herein, we investigate clinical-genomic features and outcomes among Latinos and NHW pts with ccRCC. Methods: Pts with mccRCC treated at UCSD were retrospectively identified from an institutional database. Pts with genomic sequencing on tumor tissue samples were included. Pts were categorized as Latino or NHW based on self-identification. Logistic regression was applied for the presence of divergent frequencies of somatic mutations. Cox regression models evaluated the effect of additional factors, including tumor genomic alterations and clinical features, on overall survival (OS). Results: The analysis included 135 pts with mccRCC, of whom 62 were Latinos. There were no significant differences in age at diagnosis (61 vs 62 years), BMI...

MP61-19 INCIDENCE OF ERECTILE DYSFUNCTION AND TESTOSTERONE DEFICIENCY IN TESTICULAR CANCER SURVIVORS

Thu, 5 Dec 2024 00:00:00 +0000

MP61-19 INCIDENCE OF ERECTILE DYSFUNCTION AND TESTOSTERONE DEFICIENCY IN TESTICULAR CANCER SURVIVORS

A phase 2 study of neoadjuvant PARP inhibition followed by radical prostatectomy (RP) in patients with unfavorable intermediate-risk or high-risk prostate cancer with BRCA1/2 gene alterations (NePtune).

Thu, 5 Dec 2024 00:00:00 +0000

TPS5128 Background: Patients with localized high-risk prostate cancer have an increased risk of relapse following RP. Approximately 6% of patients with high-risk disease harbor germline alterations in the DNA repair pathway, of which BRCA1/2 alterations are the most common. Patients with germline BRCA1/2 mutations have higher rates of aggressive disease, distant metastases, and worse survival compared to non-carriers. Olaparib is a PARP inhibitor which demonstrates improved overall survival in patients with metastatic castration resistant prostate cancer with BRCA1/2 germline and somatic alterations. Additionally, olaparib has demonstrated improved invasive disease-free survival as adjuvant therapy in patients with germline BRCA1/2 HER-2 negative breast cancer. Novel, multimodal treatment strategies for patients with high-risk localized prostate cancer with germline or somatic BRCA1/2 may improve outcomes for these patients. Methods: We designed a multicenter phase 2 single...

Dissecting the significance of ACP1 gene alterations in prostate cancer (PCa).

Thu, 5 Dec 2024 00:00:00 +0000

5025 Background: The acid phosphatase 1 ( ACP1) gene encodes low molecular weight protein tyrosine phosphatase (LMPTP), which is overexpressed in PCa. Previous studies demonstrate that LMPTP plays a critical role in PCa growth and metastasis and is evolving as a potential therapeutic target. Thus, we analyzed ACP1 expression in primary and metastatic PCa samples and the association of ACP1 with molecular profiles and clinical outcomes. Methods: NextGen sequencing of DNA (592-gene/whole exome) and RNA (whole transcriptome) was performed for PCa specimens (n=5028) submitted to Caris Life Sciences. ACP1-High/Low expression was defined as quartile 4 (Q4) and 1 (Q1) of RNA transcripts per million (TPM). DNA mutational profiles were analyzed for samples stratified by ACP1 expression quartiles. Gene set enrichment analysis was used to assess the Hallmark collection of cancer pathways. Tumor cell PD-L1+ status (≥2+, ≥5%; SP142) was tested by immunohistochemistry. Immune cell fractions...

Comparing the somatic, germline, and immune landscapes of upper tract urothelial carcinoma (UTUC) and UC of the bladder (UCB).

Thu, 5 Dec 2024 00:00:00 +0000

4520 Background: Molecular characterization of anatomically distinct UCs has been limited by the rarity of UTUC; however, recent advances in real-world data curation have enabled larger UTUC cohort generation. Here, we investigated the somatic, germline, and immunologic landscapes of UTUC compared to UCB. Methods: From the Tempus Database, we retrospectively analyzed de-identified next-generation sequencing data from 505 UTUC (224 ureter, 281 renal pelvis) and 2,416 UCB cases (2,379 bladder, 37 urethra). Tumors were sequenced with the Tempus xT DNA and xR RNA assays. Pathogenic somatic mutations, immune cell infiltration predicted from gene expression patterns, TMB, PD-L1 from IHC, MSI, and mismatch repair (MMR) were evaluated. Incidental germline alterations were assessed in 46 genes for patients with tumor/normal-matched (T/N) sequencing (UTUC n=285, UCB n=1,359). Chi-squared, Fisher's exact, and Wilcoxon rank-sum tests were used to assess statistical significance (p<0.05,...

12 Concordance Analysis of Tissue and Circulating Tumor DNA (ctDNA) in Renal Cell Carcinoma (RCC): Insights from a Multimodal Real-World Database

Thu, 5 Dec 2024 00:00:00 +0000

Abstract: Background: Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) has emerged as a powerful complement to tissue NGS, offering a noninvasive and serially conductible test. Its application holds promise in enhancing the assessment of spatial and temporal molecular tumor heterogeneity, thus providing valuable insights into cancer progression and treatment response. In this study, we explore the mutational landscape of renal cell carcinoma (RCC) patients through comprehensive profiling of mutations in ctDNA and matched tissue samples, aiming to elucidate the concordance and clinical significance of molecular alterations detected in both circulating and tissue-derived DNA. Methods: From the Tempus multimodal database, we retrospectively analyzed de-identified NGS data from patients with RCC that had dual tissue (Tempus xT, 648 genes)...

MP01-07 IMPACT OF CHEMOTHERAPY ON ANXIETY, DEPRESSION, AND SUICIDALITY AMONGST TESTICULAR CANCER SURVIVORS

Thu, 5 Dec 2024 00:00:00 +0000

MP01-07 IMPACT OF CHEMOTHERAPY ON ANXIETY, DEPRESSION, AND SUICIDALITY AMONGST TESTICULAR CANCER SURVIVORS

Readability Assessment of Patient Education Materials on Uro-oncological Diseases Using Automated Measures

Thu, 5 Dec 2024 00:00:00 +0000

BACKGROUND AND OBJECTIVE: Readability of patient education materials is of utmost importance to ensure understandability and dissemination of health care information in uro-oncology. We aimed to investigate the readability of the official patient education materials of the European Association of Urology (EAU) and American Urology Association (AUA). METHODS: Patient education materials for prostate, bladder, kidney, testicular, penile, and urethral cancers were retrieved from the respective organizations. Readability was assessed via the WebFX online tool for Flesch Kincaid Reading Ease Score (FRES) and for reading grade levels by Flesch Kincaid Grade Level (FKGL), Gunning Fog Score (GFS), Smog Index (SI), Coleman Liau Index (CLI), and Automated Readability Index (ARI). Layperson readability was defined as a FRES of ≥70 and with the other readability indexes <7 according to European Union recommendations. This study assessed only objective readability and no other metrics such...

Socioeconomic and Demographic Disparities in Immunotherapy Utilization for Advanced Kidney and Bladder Cancer

Thu, 5 Dec 2024 00:00:00 +0000

Objectives

Immunotherapy (IO) drugs have been increasingly utilized in locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) and urothelial carcinoma of the bladder (UC). Multiple trials have demonstrated clear survival benefit, however, there are often barriers to access for these advanced therapies which has been demonstrated in other non-urologic malignancies. The goal of this study was to assess socioeconomic and demographic factors associated with the receipt of IO for advanced ccRCC and UC.

Materials and methods

We queried the National Cancer Database (NCDB) for patients with stage IV ccRCC and UC. The study period was 2015 to 2020 for ccRCC (FDA approval date of IO) and 2017 to 2020 for UC (FDA approval date of broadened indication for IO, initial limited approval in 2016). The primary outcome of interest was receipt of IO therapy using multivariable logistic regression, adjusting for relevant socioeconomic and demographic variables.

Results

We...

Landscape analysis and oncologic outcomes in advanced urothelial carcinoma (UC) by NECTIN4 RNA expression

Thu, 5 Dec 2024 00:00:00 +0000

Landscape analysis and oncologic outcomes in advanced urothelial carcinoma (UC) by NECTIN4 RNA expression

Re: Long-term Quality of Life of Testicular Cancer Survivors Differs According to Applied Adjuvant Treatment and Tumour Type

Thu, 5 Dec 2024 00:00:00 +0000

Re: Long-term Quality of Life of Testicular Cancer Survivors Differs According to Applied Adjuvant Treatment and Tumour Type

Disparate outcomes among Latino and non-Hispanic White (NHW) patients with metastatic clear cell renal cell carcinoma (mccRCC)

Thu, 5 Dec 2024 00:00:00 +0000

Disparate outcomes among Latino and non-Hispanic White (NHW) patients with metastatic clear cell renal cell carcinoma (mccRCC)

Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): an open-label, multicentre, parallel-group, randomised, phase 2/3 trial

Thu, 5 Dec 2024 00:00:00 +0000

BACKGROUND: Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab. METHODS: NRG-HN004 was designed as an open-label, multicentre, parallel-group, randomised, phase 2/3 trial with safety lead-in conducted at 89 academic and community medical centres in North America. Eligible patients were aged 18 years or older with American Joint Committee on Cancer 8th edition stage III-IVB p16-negative HNSCC or unfavourable stage I-III p16-positive oropharyngeal or unknown primary carcinoma, who had a contraindication to cisplatin (Eastern Cooperative Oncology Group [ECOG] performance status 2, renal or hearing impairment, peripheral neuropathy, aged at least 70 years with moderate or severe comorbidity, or aged younger than 70 years with severe comorbidity)....

Surgeon factors and their association with operating room turnover time

Thu, 5 Dec 2024 00:00:00 +0000

Surgeon factors and their association with operating room turnover time

Characterization of FOLH1 Expression in Renal Cell Carcinoma

Thu, 5 Dec 2024 00:00:00 +0000

PURPOSE: Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of FOLH1 expression in RCC and their impacts on RCC outcomes. METHODS: We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation sequencing. FOLH1-high/low expression was defined as the ≥75th/<25th percentile of RNA transcripts per million (TPM). Angiogenic, T-effector, and myeloid expression signatures were calculated using previously defined gene sets. Kaplan-Meier estimates were calculated from the time of tissue collection or therapy start. RESULTS: We included 1,724 patients in the analysis. FOLH1 expression was significantly higher in clear cell (71%) compared to non-clear cell RCC tumors (19.0 versus 3.3 TPM, p < 0.001) and varied by specimen site (45% primary kidney/55% metastasis, 13.6 versus 9.9 TPM, p < 0.001). FOLH1 expression was correlated with angiogenic...

Matched tissue and circulating tumor DNA (ctDNA) analysis in renal cell carcinoma (RCC): Results from a multimodal real-world database.

Thu, 5 Dec 2024 00:00:00 +0000

4533 Background: Next generation sequencing (NGS) of ctDNA can complement tissue NGS and is a non-invasive test that can be conducted serially, with the potential to enhance assessment of spatial and temporal molecular tumor heterogeneity. Here, we investigated mutations in RCC patients from ctDNA and matched tissue genomic profiling. Methods: From the Tempus multimodal database, we retrospectively analyzed de-identified NGS data from patients (pts) with RCC that had dual tissue (Tempus xT, 648 genes) and ctDNA testing (Tempus xF, 105 genes). Pts with matched samples (collected +/- 90 days of one another) were included. Clinical characteristics and select pathogenic somatic short variants (PSSV) and copy number variants [(amplifications and deletions, two copy number losses (CNL)] were evaluated. Concordance analyses were restricted to the 105 genes tested on the ctDNA panel and further restricted to short variants, with the exception of amplifications and CNL detected by both...

Evaluation and Management of Testicular Cancer After Late Relapse

Thu, 5 Dec 2024 00:00:00 +0000

Evaluation and Management of Testicular Cancer After Late Relapse

Matched tissue and circulating tumor DNA (ctDNA) analysis in renal cell carcinoma (RCC): Results from a multimodal real-world database

Thu, 5 Dec 2024 00:00:00 +0000

Matched tissue and circulating tumor DNA (ctDNA) analysis in renal cell carcinoma (RCC): Results from a multimodal real-world database

Striving for Equity: Examining Health Disparities in Urologic Oncology

Thu, 5 Dec 2024 00:00:00 +0000

Health disparities in urologic oncology, particularly in prostate, bladder, kidney, and testicular cancers, significantly impact patient outcomes across different demographic groups. This narrative review aims to investigate the extent and drivers of these disparities, focusing on the influence of race, socioeconomic status, and geographic location on diagnosis, treatment, and survival outcomes. We conducted a comprehensive review of the existing literature and analyzed data from national cancer databases to identify patterns of inequity. Our findings reveal that minority populations, individuals with lower socioeconomic status, and those residing in underserved areas are less likely to receive timely and guideline-based care, leading to worse outcomes. This review underscores the urgent need for targeted interventions, including policy reforms, health system restructuring, enhanced community outreach, and increased funding for disparity-focused research, to ensure equitable access...

Molecular and clinical correlates of high FOLH1 (PSMA) RNA expression in primary and metastatic prostate cancer

Thu, 5 Dec 2024 00:00:00 +0000

BACKGROUND: Prostate-specific membrane antigen (PSMA; FOLH1) is a cell-surface target for diagnostics and treatment in prostate cancer. We utilized a database of molecularly-profiled prostate tumors to evaluate clinical, genomic, and immunologic correlates of high FOLH1 RNA expression. PATIENTS AND METHODS: Prostate cancer specimens (N = 7,082) underwent DNA/RNA sequencing and immunohistochemistry at Caris Life Sciences. FOLH1-High/Low expression was defined by upper/lower quartiles or median transcripts per million (TPM). Overall survival (OS) was calculated from insurance claims. RESULTS: Prostate adenocarcinoma had 2.97-fold higher FOLH1 expression compared to high grade neuroendocrine prostate cancer (q < 0.0001). Of 7,020 adenocarcinomas, 4,464 were primary prostate samples, 828 were lymph node metastases, and 1,686 were distant metastases. FOLH1 expression varied across metastatic sites (highest in lymph node and lowest in liver; 1.2-fold difference, q < 0.05). FOLH1-High...

Driver mutations associated with signatures of platinum sensitivity in germ cell tumors

Thu, 5 Dec 2024 00:00:00 +0000

We sought to evaluate the genomic and transcriptomic landscapes in primary and metastatic germ cell tumors (GCTs; N = 138) to uncover factors that drive cisplatin resistance. Prevalence was calculated for platinum-resistant alterations (PRAs; KRAS, TP53, and KIT mutations, and MDM2 amplification) and high copy number amplifications (CNA ≥ 6 copies). Tumors were designated as chemo-naïve (PreC, N = 66) or post-chemotherapy (PostC, N = 17). A transcriptomic signature associated with platinum sensitivity (PSS, high suggests increased sensitivity) was applied. KIT mutations were observed in 14.5% of primary versus 1.8% of met and 0% of lymph. TP53 mutations were identified in 10% of primary GCTs versus 17% of met and 16.7% of lymph. MDM2 CNAs were similar between sites. PRA-positive PreC GCTs had significantly lower average PSS scores compared to PRA-negative tumors. Lower PSS scores in chemo-naïve tumors were associated with PRAs, suggesting a potential mechanism for platinum resistance.

Landscape analysis and oncologic outcomes in advanced urothelial carcinoma (UC) by NECTIN4 RNA expression.

Thu, 5 Dec 2024 00:00:00 +0000

4585 Background: Advanced UC is a devastating disease, however recent advances with antibody drug conjugates (ADCs), including enfortumab vedotin (EV), have improved outcomes significantly. Currently no biomarkers are clinically available to predict response to therapy. We hypothesized that benefit from EV may correlate with mRNA expression of NECTIN4, the gene encoding the relevant cell surface antigen for EV. Therefore, we performed a landscape analysis of NECTIN4 in advanced UC and correlated expression with oncologic outcomes. Methods: Bladder and upper tract UC samples were tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing on DNA (592 genes or whole exome) and NovaSeq on RNA (whole transcriptome). UC samples were stratified by NECTIN4 mRNA levels into four quartiles. Tumor mutational burden (TMB) totaled somatic nonsynonymous mutations per tumor (high >10 mut/Mb). Insurance claims data were used to calculate survival outcomes using Kaplan-Meier estimates....

ReIGNITE Radiation Therapy Boost: A Prospective, International Study of Radiation Oncologists’ Accuracy in Contouring Prostate Tumors for Focal Radiation Therapy Boost on Conventional Magnetic Resonance Imaging Alone or With Assistance of Restriction Spectrum Imaging

Tue, 3 Dec 2024 00:00:00 +0000

PURPOSE: In a phase III randomized trial, adding a radiation boost to tumor(s) visible on MRI improved prostate cancer (PCa) disease-free and metastasis-free survival without additional toxicity. Radiation oncologists' ability to identify prostate tumors is critical to widely adopting intraprostatic tumor radiotherapy boost for patients. A diffusion MRI biomarker, called the Restriction Spectrum Imaging restriction score (RSIrs), has been shown to improve radiologists' identification of clinically significant PCa. We hypothesized that (1) radiation oncologists would find accurately delineating PCa tumors on conventional MRI challenging and (2) using RSIrs maps would improve radiation oncologists' accuracy for PCa tumor delineation. METHODS AND MATERIALS: In this multi-institutional, international, prospective study, 44 radiation oncologists (participants) and 2 expert radiologists (experts) contoured prostate tumors on 39 total patient cases using conventional MRI with or without...

Multicenter validation of an RNA-based assay to predict anti-PD-1 disease control in patients with recurrent or metastatic head and neck squamous cell carcinoma: the PREDAPT study

Wed, 27 Nov 2024 00:00:00 +0000

BACKGROUND: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors. METHODS: Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from Analysis of Pre-treatment Tumor biopsies (PREDAPT), conducted across 17 US healthcare systems. PREDAPT aimed to validate OncoPrism-HNSCC, a clinical biomarker assay predictive of disease control in patients with recurrent or metastatic HNSCC treated with anti-PD-1 immune checkpoint...

Opioid tapering in older cancer survivors does not increase psychiatric or drug hospitalization rates

Sat, 23 Nov 2024 00:00:00 +0000

BACKGROUND: Opioid tapering in the general population is linked to increases in hospitalizations or emergency department visits related to psychiatric or drug-related diagnoses. Cancer survivors represent a unique population with different opioid indications, prescription patterns, and more frequent follow-up care. This study sought to describe patterns of opioid tapering among older cancer survivors and to test the hypothesis of whether older cancer survivors face increased risks of adverse events with opioid tapering. METHODS: Using the Surveillance, Epidemiology and End Results Medicare-linked database, we identified 15 002 Medicare-beneficiary cancer survivors diagnosed between 2010 and 2017 prescribed opioids consistently for at least 6 months after their cancer diagnosis. Tapering was defined as a binary time-varying event occurring with any monthly oral morphine equivalent reduction of 15% or more from the previous month. Primary diagnostic billing codes associated with...

Development and Validation of the Veterans Affairs Eosinophilic Esophagitis Cohort

Wed, 13 Nov 2024 00:00:00 +0000

BACKGROUND & AIMS: Gaps remain in understanding the epidemiology of eosinophilic esophagitis (EoE). Our aim was to identify and validate a national cohort of individuals with EoE using Veterans Health Administration (VHA) data. METHODS: We used 2 validation strategies to develop algorithms that identified adults with EoE between 1999 and 2020. The first validation strategy applied International Classification of Diseases (ICD) code algorithms to a base cohort of individuals who underwent esophagogastroduodenoscopy with esophageal biopsy specimens. The second applied ICD code algorithms to a base cohort of all individuals in the VHA. For each ICD algorithm applied, a random sample of candidate EoE cases and non-EoE controls were selected and the charts were reviewed manually by a blinded reviewer. Each algorithm was modified iteratively until the prespecified diagnostic accuracy end point (95% confidence lower bound for a positive predictive value [PPV], >88%) was achieved....

Low PD-L1 expression, MAP2K2 alterations, and enriched HPV gene signatures characterize brain metastases in head and neck squamous cell carcinoma

Mon, 11 Nov 2024 00:00:00 +0000

BackgroundBrain metastasis (BM) is a rare but severe complication of head and neck squamous cell carcinoma (HNSCC), with limited knowledge of molecular characteristics and immunogenicity.MethodsWe analyzed 61 cases of HNSCC-BM from three academic institutions (n = 24) and Foundation Medicine Inc (FMI, n = 37). A subset of cases underwent next-generation sequencing, multiple immunofluorescence, and proximity ligation sequencing. Gene enrichment analysis compared alterations in FMI BM samples (n = 37) with local samples (n = 4082).ResultsDemographics included: median age of 59 years, 75% male, 55% current/former smokers, 75% oropharyngeal primary, and 67% human papillomavirus (HPV) +. ATM (54%), KMT2A (54%), PTEN (46%), RB1 (46%), and TP53 (46%) were frequently altered in BM samples from academic centers (62% HPV/p16+). Structural rearrangements ranged from 9 to 90 variants by proximity ligation sequencing. BMs had low densities of CD8+, PD-1+, PD-L1+, and FOXP3 + cells, and 92%...

Hub-and-Spoke centralized intervention to optimize colorectal cancer screening and follow-up: A pragmatic, cluster-randomized controlled trial protocol

Sat, 9 Nov 2024 00:00:00 +0000

BACKGROUND: Guidelines recommend screening for colorectal cancer (CRC), but participation and abnormal test follow up rates are suboptimal, with disparities by demography. Evidence-based interventions exist to promote screening, but community adoption and implementation are limited. METHODS: The San Diego Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) program is an academic-community partnership testing regional implementation of a Hub-and-Spoke model for increasing CRC screening and follow-up. The "hub" is a non-academic, non-profit organization that includes 17 community health center (CHC) systems, serving over 190 rural and urban clinic sites. The "spokes" are 3 CHC systems that oversee 11-28 clinics each, totaling over 60 clinics. Using a cluster-randomized trial design, 9 clinics were randomized to intervention and 16 to usual care. Within intervention clinics, approximately 5000 eligible patients not up-to-date with CRC screening...

Establishing a Regional Health System and Community-Based Organization Social Care Coordination Network: An Application of Geospatial Analysis

Tue, 5 Nov 2024 00:00:00 +0000

INTRODUCTION: Adverse social determinants of health have been shown to be associated with a greater chance of developing chronic conditions. Although there has been increased focus on screening for health-related social needs (HRSNs) in health care delivery systems, it is seldom examined if the provision of needed services to address HRSNs is sufficiently available in communities where patients reside. METHODS: The authors used geospatial analysis to determine how well a newly formed health system and community-based organizations (CBOs) social care coordination network covered the areas in which a high number of patients experiencing HRSNs live. Geospatial clusters (hotspots) were constructed for Kaiser Permanente Northwest members experiencing any of the following 4 HRSNs: transportation needs, housing instability, food insecurity, or financial strain. Next, a geospatial polygon was calculated indicating whether a member could reach a social care provider within 30 minutes of...

Deep Learning Segmentation of Infiltrative and Enhancing Cellular Tumor at Pre- and Posttreatment Multishell Diffusion MRI of Glioblastoma.

Tue, 5 Nov 2024 00:00:00 +0000

Purpose To develop and validate a deep learning (DL) method to detect and segment enhancing and nonenhancing cellular tumor on pre- and posttreatment MRI scans in patients with glioblastoma and to predict overall survival (OS) and progression-free survival (PFS). Materials and Methods This retrospective study included 1397 MRI scans in 1297 patients with glioblastoma, including an internal set of 243 MRI scans (January 2010 to June 2022) for model training and cross-validation and four external test cohorts. Cellular tumor maps were segmented by two radiologists on the basis of imaging, clinical history, and pathologic findings. Multimodal MRI data with perfusion and multishell diffusion imaging were inputted into a nnU-Net DL model to segment cellular tumor. Segmentation performance (Dice score) and performance in distinguishing recurrent tumor from posttreatment changes (area under the receiver operating characteristic curve [AUC]) were quantified. Model performance in predicting...

Preferences for Public Health Messaging Related to Bladder Health in Adolescent and Adult Women

Tue, 5 Nov 2024 00:00:00 +0000

Objective: The purpose of this analysis was to explore adolescent and adult women's preferences for the content and delivery of public health messaging around bladder health. Materials and Methods: This was a directed content analysis of focus group data from the Study of Habits, Attitudes, Realities, and Experiences, which explored adolescent and adult women's experiences, perceptions, beliefs, knowledge, and behaviors related to bladder health and function across the life course. This article reports an analysis of the "Public Health Messaging" code, which includes participants' views on what information is needed about bladder health, attributes of messaging, and preferred locations and delivery methods. Results: Forty-four focus groups were conducted with 360 participants (ages 11-93 years) organized into six age groups. Across age groups, participants wanted messaging on maintaining bladder health and preventing bladder problems....

Spending for Advanced Cancer Diagnoses: Comparing Recurrent Versus De Novo Stage IV Disease.

Mon, 4 Nov 2024 00:00:00 +0000

PURPOSE: Spending for patients with advanced cancer is substantial. Past efforts to characterize this spending usually have not included patients with recurrence (who may differ from those with de novo stage IV disease) or described which services drive spending. METHODS: Using SEER-Medicare data from 2008 to 2013, we identified patients with breast, colorectal, and lung cancer with either de novo stage IV or recurrent advanced cancer. Mean spending/patient/month (2012 US dollars) was estimated from 12 months before to 11 months after diagnosis for all services and by the type of service. We describe the absolute difference in mean monthly spending for de novo versus recurrent patients, and we estimate differences after controlling for type of advanced cancer, year of diagnosis, age, sex, comorbidity, and other factors. RESULTS: We identified 54,982 patients with advanced cancer. Before diagnosis, mean monthly spending was higher for recurrent patients (absolute difference: breast,...

Building Community Engagement Capacity in a Transdisciplinary Population Health Research Consortium.

Mon, 21 Oct 2024 00:00:00 +0000

Community engagement has been named a research priority by the National Institutes of Health, and scholars are calling for community engagement as an approach to address racism and equity in science. Robust community-engaged research can improve research quality, increase inclusion of traditionally marginalized populations, broaden the impact of findings on real-life situations, and is particularly valuable for underexplored research topics. The goal of this paper is to describe lessons learned and best practices that emerged from community engagement in a multi-institution population health research consortium. We describe how a foundation was laid to enable community-engaged research activities in the consortium, using a staged and stepped process to build and embed multi-level community-engaged research approaches.. We staged our development to facilitate (a) awareness of community engagement among consortium members, (b) the building of solidarity and alliances, and (c) the...

A pragmatic randomized trial of mailed fecal immunochemical testing to increase colorectal cancer screening among low‐income and minoritized populations

Mon, 23 Sep 2024 00:00:00 +0000

BACKGROUND: Colorectal cancer (CRC) screening is underused, particularly among low-income and minoritized populations, for whom the coronavirus disease 2019 (COVID-19) pandemic has challenged progress in achieving equity. METHODS: A hub-and-spoke model was used. The hub was a nonacademic organization and the spokes were three community health center (CHC) systems overseeing numerous clinic sites. Via a cluster-randomized trial design, nine clinic sites were randomized to intervention and 16 clinic sites were randomized to usual care. Patient-level interventions included invitation letters, mailed fecal immunochemical tests (FITs), and call/text-based reminders. Year 1 intervention impact, which took place during the COVID-19 pandemic, was assessed as the proportion completing screening among individuals not up to date at baseline, which compared intervention and nonintervention clinics accounting for intraclinic cluster variation; confidence intervals (CIs) around differences...

Higher tumor mutational burden and PD-L1 expression correlate with shorter survival in hematologic malignancies

Thu, 19 Sep 2024 00:00:00 +0000

Background: The prognostic implications of tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are poorly studied in hematologic malignancies. Objectives: This study aimed to better understand the characteristics and prognostic value of TMB and PD-1/PD-L1 in hematologic malignancies. Design: This real-world study was conducted among patients with hematologic malignancies who had next-generation sequencing (NGS) (Foundation Medicine) at the University of California San Diego Moores Cancer Center (2014-2018). Methods: TMB was measured by NGS. PD-L1 expression (tumor proportion score, TPS) was measured by immunohistochemistry (classified as high (⩾50%), low (1-49%), and negative (<1%)). Data was curated from the electronic medical records. Results: In 388 evaluable patients, the most common diagnoses were B-cell non-Hodgkin lymphoma (NHL) (35%) and Philadelphia chromosome-negative myeloproliferative disorders (16%). Median TMB was 1.6 mutations/Mb (range,...

Risk of Incident and Fatal Colorectal Cancer After Young-Onset Adenoma Diagnosis: A National Cohort Study

Wed, 4 Sep 2024 00:00:00 +0000

INTRODUCTION: Colorectal cancer (CRC) incidence and mortality rates are increasing in adults aged <50 years. Young-onset adenoma (YOA)-adenoma detected in adults younger than 50 years-may signify increased CRC risk, but this association has not been widely studied. Our aim was to compare the risk of incident and fatal CRC in adults aged <50 years with YOA diagnosis compared with those with a normal colonoscopy. METHODS: We conducted a cohort study of US Veterans aged 18-49 years who received colonoscopy between 2005 and 2016. The primary exposure of interest was YOA. Primary outcomes included incident and fatal CRC. We used Kaplan-Meier curves to calculate cumulative incident and fatal CRC risk and Cox models to examine relative CRC risk. RESULTS: The study cohort included 54,284 Veterans aged <50 years exposed to colonoscopy, among whom 13% (n = 7,233) had YOA at start of follow-up. Cumulative 10-year CRC incidence was 0.11% (95% confidence interval [CI]: 0.00%-0.27%)...

Agent orange exposure and prostate cancer risk in the million veteran program

Sat, 31 Aug 2024 00:00:00 +0000

BACKGROUND: The US government considers veterans to have been exposed to Agent Orange if they served in Vietnam while the carcinogen was in use, and these veterans are often deemed at high risk of prostate cancer (PCa). Here, we assess whether presumed Agent Orange exposure is independently associated with increased risk of any metastatic or fatal PCa in a diverse Veteran cohort still alive in the modern era (at least 2011), when accounting for race/ethnicity, family history, and genetic risk. PATIENTS AND METHODS: Participants in the Million Veteran Program (MVP; enrollment began in 2011) who were on active duty during the Vietnam War era (August 1964-April 1975) were included (n = 301,470). Agent Orange exposure was determined using the US government definition. Genetic risk was assessed via a validated polygenic hazard score. Associations with age at diagnosis of any PCa, metastatic PCa, and death from PCa were assessed via Cox proportional hazards models. RESULTS AND INTERPRETATION:...

Ultraprocessed Foods and Kidney Disease Progression, Mortality, and Cardiovascular Disease Risk in the CRIC Study

Tue, 13 Aug 2024 00:00:00 +0000

RATIONALE & OBJECTIVE: Ultraprocessed foods are widely consumed in the United States and are associated with cardiovascular disease (CVD), mortality, and kidney function decline in the general population. We investigated associations between ultraprocessed food intake and chronic kidney disease (CKD) progression, all-cause mortality, and incident CVD in adults with chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Chronic Renal Insufficiency Cohort Study participants who completed baseline dietary questionnaires. EXPOSURE: Ultraprocessed food intake (in servings per day) classified according to the NOVA system. OUTCOMES: CKD progression (≥50% decrease in estimated glomerular filtration rate [eGFR] or initiation of kidney replacement therapy), all-cause mortality, and incident CVD (myocardial infarction, congestive heart failure, or stroke). ANALYTICAL APPROACH: Cox proportional hazards models adjusted for demographic, lifestyle,...

Cytomegalovirus Retinitis in an Eye with Unilateral Retinoblastoma: A Case Report

Fri, 2 Aug 2024 00:00:00 +0000

Introduction: Cytomegalovirus (CMV) retinitis in the setting of pediatric retinoblastoma is exceedingly unusual. Here, we present the first reported case of CMV retinitis in an enucleated eye with retinoblastoma after chemotherapy in the western hemisphere. Case Presentation: A 2-year-old Hispanic male without a family history of retinoblastoma presented with a 3-month history of right eye exotropia and squinting. Clinical examination revealed dense white vitreous opacities in the right eye. Ocular oncology evaluation unveiled an exudative retinal detachment with vitreous seeds, subretinal seeding, and a tumor emanating from the retina in the superonasal quadrant of the right eye. The patient was diagnosed with unilateral Group D retinoblastoma, and RB1 sequencing revealed a pathogenic variant with mosaicism. Treatment involved systemic chemotherapy, intravitreal chemotherapy, and cryotherapy. However, the patient developed a rhegmatogenous retinal detachment with diffuse vitreous...

Protocol to study the immune profile of syngeneic mouse tumor models

Sat, 20 Jul 2024 00:00:00 +0000

Flow cytometry, single-cell RNA sequencing, and other analyses enable us to capture immune profiles of the tumor microenvironment. Here, we present a protocol to characterize the immune profile of tumor-bearing mice. We describe steps for establishing mouse models and preparing single-cell suspensions from tumor tissue and other immune-related organs, which can be further analyzed by flow cytometry and other omics assays. We then detail procedures for staining, flow cytometry analysis, and phenotyping of the immune cell populations. For complete details on the use and execution of this protocol, please refer to Miyauchi et al.¹.

Comparison of synthesized and acquired high b-value diffusion-weighted MRI for detection of prostate cancer

Tue, 16 Jul 2024 00:00:00 +0000

BackgroundHigh b-value diffusion-weighted images (DWI) are used for detection of clinically significant prostate cancer (csPCa). This study qualitatively and quantitatively compares synthesized DWI (sDWI) to acquired (aDWI) for detection of csPCa.MethodsOne hundred fifty-one consecutive patients who underwent prostate MRI and biopsy were included in the study. Axial DWI with b = 0, 500, 1000, and 2000 s/mm2 using a 3T clinical scanner using a 32-channel phased-array body coil were acquired. We retrospectively synthesized DWI for b = 2000 s/mm2 via extrapolation based on mono-exponential decay, using b = 0 and b = 500 s/mm2 (sDWI500) and b = 0, b = 500 s/mm2, and b = 1000 s/mm2 (sDWI1000). Differences in signal intensity between sDWI and aDWI were evaluated within different regions of interest (prostate alone, prostate plus 5 mm, 30 mm and 70 mm margin and full field of view). The maximum DWI value within each ROI was evaluated for prediction...

A Retrospective Observational Analysis of Overall Survival with Sipuleucel-T in Medicare Beneficiaries Treated for Advanced Prostate Cancer

Tue, 16 Jul 2024 00:00:00 +0000

IntroductionSince sipuleucel-T approval in 2010, the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) now includes the androgen-receptor signaling pathway inhibitors (ASPIs) abiraterone acetate or enzalutamide. In 2013 and 2014, these oral agents were approved for use in men with metastatic prostate cancer who had minimal to no symptoms. We compared overall survival (OS) in men who received their first mCRPC treatment using the Medicare Fee-for-Service 100% administrative claims research dataset with patient-level linkage to the National Death Index.MethodsThis retrospective cohort analysis (January 2013 to December 2017) included men who were chemo-naïve at treatment start in 2014 and who had continuous Medicare Parts A, B, and D eligibility during the 3-year observation period. We compared: first-line sipuleucel-T vs. first-line ASPIs and any-line sipuleucel-T vs. any-line ASPIs (without sipuleucel-T). We used a multivariable regression model to...