To describe the development of a web-based, theory-guided narrative intervention that replaces conventional pre-test genetic counseling for women at elevated breast cancer risk.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Final overall survival (OS) in SOPHIA (ClinicalTrials.gov identifier: NCT02492711), a study of margetuximab versus trastuzumab, both with chemotherapy, in patients with previously treated human epidermal growth factor receptor 2-positive advanced breast cancer, is reported with updated safety. Overall, 536 patients in the intention-to-treat population were randomly assigned to margetuximab (15 mg/kg intravenously once every 3 weeks; n = 266) plus chemotherapy or trastuzumab (6 mg/kg intravenously once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy. Primary end points were progression-free survival, previously reported, and OS. Final OS analysis was triggered by 385 prespecified events. The median OS was 21.6 months (95% CI, 18.89 to 25.07) with margetuximab versus 21.9 months (95% CI, 18.69 to 24.18) with trastuzumab (hazard ratio [HR], 0.95; 95% CI, 0.77 to 1.17; P = .620). Preplanned, exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients versus trastuzumab (median OS, 23.6 v 19.2 months; HR, 0.72; 95% CI, 0.52 to 1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients versus margetuximab (median OS, 31.1 v 22.0 months; HR, 1.77; 95% CI, 1.01 to 3.12). Margetuximab safety was comparable with trastuzumab. Final overall OS analysis did not demonstrate margetuximab advantage over trastuzumab. Margetuximab studies in patients with human epidermal growth factor receptor 2-positive breast cancer with different CD16A allelic variants are warranted.

High levels of ERBB2 (formerly HER2)-specific type 1 T cells in the peripheral blood are associated with favorable clinical outcomes after trastuzumab therapy; however, only a minority of patients develop measurable ERBB2 immunity after treatment. Vaccines designed to increase ERBB2-specific T-helper cells could induce ERBB2 immunity in a majority of patients.

The extracellular matrix (ECM) is a vital component of the tumor microenvironment, which interplays with stromal and tumor cells to stimulate the capacity of cancer cells to proliferate, migrate, invade, and undergo angiogenesis. Nevertheless, the crucial functions of ECM-related genes (ECMGs) in pancreatic adenocarcinoma (PAAD) have not been systematically evaluated. Hence, a comprehensive evaluation of the ECMGs is required in pan-cancer, especially in PAAD. First, a pan-cancer overview of ECMGs was explored through the integration of expression profiles, prognostic values, mutation information, methylation levels, and pathway-regulation relationships. Seven ECMGs (i.e. LAMB3, LAMA3, ITGB6, ITGB4, ITGA2, LAMC2, and COL11A1) were identified to be hub genes of PAAD, which were obviously up-regulated in PAAD and considerably linked to tumor stage as well as prognosis. Subsequently, patients with PAAD were divided into 3 clusters premised on ECMG expression and ECM scores. Cluster 2 was the subtype with the best prognosis accompanied by the lowest ECM scores, further verifying ECM's significant contribution to the pathophysiological processes of PAAD. Significant differences were observed for oncogene and tumor suppressor gene expression, immune microenvironment, and chemotherapy sensitivity across three ECM subtypes. After applying a variety of bioinformatics methods, a novel and robust ECM-associated mRNA-lncRNA-based prognostic panel (ECM-APP) was developed and validated for accurately predicting clinical outcomes of patients with PAAD. Patients with PAAD were randomly categorized into the train, internal validation, and external validation cohorts; meanwhile, each patient was allocated into high-risk (unfavorable prognosis) and low-risk (favorable prognosis) populations premised on the expression traits of ECM-related mRNAs and lncRNAs. The discrepancy in the tumor mutation burden and immune microenvironment might be responsible for the difference in prognoses across the high-risk and low-risk populations. Overall, our findings identified and validated seven ECMGs remarkably linked to the onset and progression of PAAD. ECM-based molecular classification and prognostic panel aid in the prognostic assessment and personalized intervention of patients with PAAD.

Obtaining comprehensive family health history (FHH) to inform colorectal cancer (CRC) risk management in primary care settings is challenging.

Skin cancer has become increasingly common among young adults; however, this population does not consistently adhere to recommended methods for preventing the disease. Interventions in college settings have relied on appearance-focused appeals and have not been able to examine the cumulative effect of multiple behavior change and skin cancer risk communication strategies. The goal of the current study was to examine the unique and combined impacts of personalized ultraviolet (UV) radiation photographs, genetic testing for skin cancer risk, and general skin cancer prevention education. Participants were randomly assigned to one of four conditions: (1) skin cancer prevention education, (2) education + UV photo, (3) education + genetic testing, and (4) education + UV photo + genetic testing. Self-reported sun protection, tanning, and sunburn were assessed at baseline, immediately post-intervention, and 1 month post-intervention. The findings indicated benefits of the interventions to skin cancer prevention behaviors in the overall sample; however, the combined (UV photo + genetic testing) intervention had the most consistent positive effects on behaviors. Intervention effects were distinct across seasons. These results suggest that interventions containing multiple skin cancer risk communication strategies hold promise in benefitting health-promoting behavior changes in an at-risk, young adult population.Trial Registration Number: NCT03979872; Registered 6/5/2019.

ARIEL3 (NCT01968213) is a placebo-controlled randomized trial of the poly(ADP-ribose) polymerase inhibitor rucaparib as maintenance treatment in patients with recurrent high-grade ovarian carcinoma who responded to their latest line of platinum therapy. Rucaparib improved progression-free survival across all predefined subgroups. Here, we present an exploratory analysis of clinical and molecular characteristics associated with exceptional benefit from rucaparib.

Adverse childhood experiences (ACEs, i.e., abuse, neglect, household dysfunction) represent a potential risk factor for a wide range of long-lasting diseases and shorter life expectancy. We recently described a 1-week residential group program, based on mindfulness training, artistic expression and EMDR group therapy, that significantly reduced PTSD-related symptoms and increased attention/awareness-related outcomes in adolescent girls with multiple ACEs in a randomized controlled study. Since epigenetic mechanisms (i.e., DNA methylation) have been associated with the long-lasting effects of ACEs, the present report extends these prior findings by exploring genome-wide DNA methylation changes following the program. Saliva samples from all participants (n = 44) were collected and genomic DNA was extracted prior (T1) and following (T2) the intervention. Genome-wide DNA methylation analysis using the MethylationEPIC beadchip array (Illumina) revealed 49 differentially methylated loci (DML; p value < 0.001; methylation change > 10%) that were annotated to genes with roles in biological processes linked to early childhood adversity (i.e., neural, immune, and endocrine pathways, cancer and cardiovascular disease). DNA sequences flanking these DML showed significant enrichment of transcription factor binding sites involved in inflammation, cancer, cardiovascular disease, and brain development. Methylation changes in SIRT5 and TRAPPC2L genes showed associations with changes in trauma-related psychological measures. Results presented here suggest that this multimodal group program for adolescents with multiple victimization modulates the DNA methylome at sites of potential relevance for health and behavioral disorders associated with ACEs.

Cediranib, a pan-vascular endothelial growth factor receptor inhibitor, suppresses expression of homologous recombination repair (HRR) genes and increases sensitivity to poly-(ADP-ribose) polymerase inhibition in preclinical models. We investigated whether cediranib combined with olaparib improves the clinical outcomes of patients with prostate cancer.

Outcomes are poor in patients with HER2-negative, advanced gastric or gastro-oesophageal junction adenocarcinomas. In this study, we investigated efficacy and safety of the first-in-class, afucosylated, humanised IgG1 anti-fibroblast growth factor receptor 2 isoform IIb (FGFR2b) monoclonal antibody bemarituzumab with modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma.

To investigate the clinical application value of radiomics features based on preoperative magnetic resonance imaging for predicting B-Raf proto-oncogene serine/threonine-protein (BRAF) V600E mutation in pediatric low-grade gliomas.

Immune checkpoint blockade (ICB) results in radiologic tumour response dynamics that differ from chemotherapy efficacy measures and require an early signal of clinical utility.

The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety.

We present 5-year results from CheckMate 227 Part 1, in which nivolumab plus ipilimumab improved overall survival (OS) versus chemotherapy in patients with metastatic non-small-cell lung cancer, regardless of tumor programmed death ligand 1 (PD-L1) status.

In breast cancer (BC) patients, the involvement of four or more lymph nodes (LN) is an indication of regional irradiation. The optimal treatment strategy remains unclear when fewer nodes are involved and lymphadenectomy is not performed. We designed a clinical trial to show the non-inferiority of Incidental (INC) compared to intentional (INT) irradiation of axillary nodes in patients with early-stage BC and low burden LN involvement.

The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non-small-cell lung cancer (NSCLC).

Necroptosis is a kind of programmed necrosis mode that plays a double-edged role in tumor progression. However, the role of necroptosis-related Messenger RNA (mRNA) in predicting the prognosis and immune response of cervical squamous carcinoma and adenocarcinoma (CESC) has not been fully studied. Firstly, the incidence of somatic mutation rate and copy number variation for 74 necroptosis-related mRNAs (NRmRNAs) were analyzed. Secondly, CESC patients were divided into four stable clusters based on the consensus clustering results and analyzed for correlations with a series of clinical factors. Subsequently, a total of 291 The Cancer Genome Atlas samples were randomly divided into either training or validation cohorts. A Cox proportional hazard model consisting of three NRmRNAs (CXCL8, CLEC9A, and TAB2) was constructed by univariate, least absolute shrinkage and selection operator and multivariate COX regression analysis to identify the prognosis and immune response. Its performance and stability were further validated in another testing dataset (GSE44001) from Gene Expression Omnibus database. The results of the receiver operating characteristic curve, principal component analysis, t-SNE, and nomogram indicated that the prognostic model we constructed can serve as an independent prognostic factor. The combination of the prognostic model and the classic TNM staging system could improve the performance in predicting the survival of CESC patients. In addition, differentially expressed genes from high and low-risk patients are screened by R software for functional analysis and pathway enrichment analysis. Besides, single-sample gene set enrichment analysis revealed that tumor-killing immune cells were reduced in the high-risk group. Moreover, patients in the low-risk group are more likely to benefit from immune checkpoint inhibitors. The analysis of tumor immune dysfunction and exclusion scores, M6A-related genes, stem cell correlation and Tumor mutational burden data with clinical information has quantified the expression levels of NRmRNAs between the two risk subgroups. According to tumor immune microenvironment scores, Spearman's correlation analysis, and drug sensitivity, immunotherapy may have a higher response rate and better efficacy in patients of the low-risk subgroup. In conclusion, we have reported the clinical significance of NRmRNAs for the prognosis and immune response in CESC patients for the first time. Screening of accurate and effective prognostic markers is important for designing a multi-combined targeted therapeutic strategy and the development of individualized precision medicine.

Approximately 20% of men with metastatic castration-sensitive prostate cancer (mCSPC) progress within 1 year of treatment, and biomarkers to identify them up front are lacking. In a randomized phase III trial in men with mCSPC (SWOG S1216), higher baseline circulating tumor cells (CTCs) were prognostic of inferior outcomes. We aimed to validate these findings and interrogate corresponding tumor genomic profiles. Consecutively seen men with newly diagnosed mCSPC undergoing systemic therapy and baseline CTC enumeration by CellSearch assay were included. Gene alterations were determined by comprehensive genomic profiling of tumor tissue by Clinical Laboratory Improvement Amendments-certified lab. The relationship between categorized CTC counts and both progression-free survival (PFS) and overall survival (OS) was assessed in the context of Cox proportional hazards models, both unadjusted and adjusted for age, Gleason score, PSA at androgen-deprivation therapy initiation, disease volume, de novo status, treatment intensification, and number of altered genes. Overall, 103 patients were included in the analysis. On multivariate analysis high CTCs (≥ 5 vs. 0) were associated with poorer PFS [HR, 4.52; 95% confidence interval (CI), 1.84-11.11; P = 0.001) and OS (HR, 3.59; 95% CI, 0.95-13.57; P = 0.060). Patients with higher CTC counts had a greater number of altered genes and total number of alterations (all P < 0.02). In this article, for the first time, we externally validate the association of higher CTC counts with inferior survival outcomes in men with mCSPC and show a distinct associated tumor genomic landscape. These findings may improve prognostication, patient counseling, and treatment selection in men with mCSPC.

Investigate whether adjuvant everolimus, an mTOR inhibitor, improves progression-free survival (PFS) in advanced-stage head and neck squamous cell carcinoma (HNSCC) and provide outcomes related to correlative biological factors associated with disease control.

In advanced oestrogen receptor-positive, HER2-negative breast cancer, acquired resistance to aromatase inhibitors frequently stems from ESR1-mutated subclones, which might be sensitive to fulvestrant. The PADA-1 trial aimed to show the efficacy of an early change in therapy on the basis of a rising ESR1 mutation in blood (bESR1mut), while assessing the global safety of combination fulvestrant and palbociclib.