Annals of Surgical Oncology Landmark Series Disparities in Surgical Oncology: Breast Cancer.

Breast cancer mortality rates have declined steadily over the past 40 years, as enhanced screening has shifted the balance of new diagnoses to curable, early-stage cancers while advances in systemic therapy have yielded improved and increasingly durable outcomes even for locally advanced and metastatic disease. However, this reduction in mortality has not been equitably distributed among all racial groups, and there continue to be significant racial and ethnic disparities. In this review, we summarize research that has contributed to our understanding of disparities in breast surgical oncology across all racial/ethnic groups, however, given that the most egregious disparities exist among Black women, our review will involve considerable focus on this racial group.

Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial.

Breast cancer recurrence may arise from dormant disseminated tumor cells (DTCs) that persist in bone marrow and other sites. Clinically, DTCs are independently associated with breast cancer recurrence and death. Preclinical studies in mouse models identified autophagy and mammalian target of rapamycin (mTOR) signaling as critical mechanisms of tumor dormancy and escape.

Factors Related to Long-Term Caregiving Burden Among Chimeric Antigen Receptor (CAR) T-Cell Recipients and Their Informal Caregivers.

Context: Caregivers are essential in the care of CAR T-cell patients, especially immediately before and after CAR T-cell therapy. However, the long-term CAR T-cell therapy caregiving implications are understudied.

Objectives: We aimed to characterize long-term caregiver health-related quality of life (HRQoL) and caregiving burden and understand the relationship between long-term caregiving burden and patient-reported HRQoL, cognitive function, and symptom burden.

NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in solitary fibrous tumors.

The pathogenesis of many rare tumor types is poorly understood, preventing the design of effective treatments. Solitary fibrous tumors (SFTs) are neoplasms of mesenchymal origin that affect 1/1,000,000 individuals every year and are clinically assimilated to soft tissue sarcomas. SFTs can arise throughout the body and are usually managed surgically.

Belantamab mafodotin does not induce B-cell maturation antigen loss or systemic immune dysfunction in multiple myeloma.

Various drug classes target B-cell maturation antigen (BCMA) including chimeric antigen receptor T-cell (CAR-T) therapies, bispecific antibodies (bsAbs), and antibody-drug conjugates (ADCs). Outcomes with CAR-T and bsAb therapies in multiple myeloma (MM) have been affected by T-cell exhaustion, and abrogated expression/mutation of the BCMA target has been observed with anti-BCMA therapies. Optimal anti-BCMA sequencing strategies are needed to improve long-term clinical outcomes.

Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cells.

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 elicits remarkable clinical efficacy in B cell malignancies, but many patients relapse owing to failed expansion and/or progressive loss of CAR-T cells. We recently reported a strategy to potently restimulate CAR-T cells in vivo, enhancing their functionality by administration of a vaccine-like stimulus comprised of surrogate peptide ligands for a CAR linked to a lymph node-targeting amphiphilic PEG-lipid (amph-vax). Here we demonstrate a general strategy to discover and optimize peptide mimotopes enabling amph-vax generation for any CAR.

Quantitative Evaluation of AI-based Organ Segmentation Across Multiple Anatomical Sites Using Eight Commercial Software Platforms.

Purpose: To evaluate organs-at-risk (OARs) segmentation variability across eight commercial AI-based segmentation software using independent multi-institutional datasets, and to provide recommendations for clinical practices utilizing AI-segmentation.

Methods: 160 planning CT image sets from four anatomical sites: head-and-neck, thorax, abdomen and pelvis were retrospectively pooled from three institutions. Contours for 31 OARs generated by the software were compared to clinical contours using multiple accuracy metrics, including: Dice similarity coefficient (DSC), 95 Percentile of Hausdorff distance (HD95), surface DSC, as well as relative added path length (RAPL) as an efficiency metric.

An eHealth Delivery Alternative for Cancer Genetic Testing for Hereditary Predisposition in Patients With Metastatic Cancers: Protocol for a Randomized Trial.

Background: Germline BRCA1 and BRCA2 testing is a standard evidence-based practice, with established risk reduction and cancer screening guidelines for genetic carriers. With Food and Drug Administration approval for poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors in patients with metastatic breast, ovarian, pancreatic, and prostate cancer, there is an additional therapeutic rationale for testing all patients with these cancers for germline BRCA1 and BRCA2 mutations. However, many at-risk patients do not have access to genetic services, leaving many genetic carriers unidentified.

"What you're hearing from all of us is simplify the language": Patient perspectives on biomarker testing in ovarian cancer.

Objective: To examine the views of patients with ovarian cancer on biomarker (somatic) and genetic testing and existing patient-facing materials.

Methods: We recruited patients with ovarian cancer for virtual focus groups and assessed patient experiences and knowledge of genetic and biomarker testing. We focused on themes of fear, knowledge, financial issues, and communication between patients and providers.

Quality or Quantity of Life? Treatment Priorities in Older Adults with Cancer in the community.

Older adults with cancer often face decisions about prioritizing quality of life, survival, or both. In this prospective study of 181 patients aged ≥65 at a community cancer center, patients completed a geriatric assessment that included a validated trade-off question: "Maintaining my quality of life is more important to me than living longer." Preferences were categorized as prioritizing quality of life, quantity of life, or both.

Pathogenic germline variants in a racially diverse real-world cohort of prostate cancer patients.

Importance: Pathogenic germline variant (PGV) rates in cancer risk genes and their association with clinical pathological features inform genetic testing practices for prostate cancer (PCa) patients.

Objective: To determine the rate of PCa risk gene PGVs in a real-world, diverse cohort of PCa patients and identify clinical predictors of carrier status.

Design Setting Participants Main Outcomes And Measures: Genetic testing results for 12 PCa risk genes, clinical, pathological, and family history of cancer variables were abstracted from clinical records for 1032 PCa patients who met National Comprehensive Cancer Network (NCCN) genetic testing criteria in oncology clinics and 3602 PCa patients who underwent testing in the VA National Precision Oncology Program (VA-NPOP).

Variation at the R181 residue of p53 confers loss of p53 DNA binding cooperativity with the retention of mitochondrial-associated apoptosis.

The p53 tumor suppressor binds DNA cooperatively as a tetramer, mediated by salt-bridge interactions between p53 residues E180 and R181. Variants at the R181 residue are one of the most identified pathogenic variants by germline genetic testing. We show that families with p.

Clinical and molecular dissection of CAR T cell resistance in pancreatic cancer.

Patients with advanced pancreatic ductal adenocarcinoma (PDAC) have a median survival of less than a year, highlighting the urgent need for treatment advancements. We report on a phase 1 clinical trial assessing the safety and feasibility of intravenous and local administration of anti-mesothelin CAR T cells in patients with advanced PDAC. While therapy is well tolerated, it demonstrates limited clinical efficacy.

Engineering Nanoparticles for Gynecologic Cancer Therapy.

The significant morbidity and mortality of gynecologic cancers places a substantial burden on global healthcare and creates an urgent need for new treatment modalities. Here, we explore the emerging role of nanoparticles in treating gynecologic cancers, specifically ovarian, cervical, and endometrial cancers. These diseases are often diagnosed after they have metastasized, developed multidrug resistance, and formed immunosuppressive tumor microenvironments, hampering the effectiveness of traditional debulking surgery and chemotherapy.

Checkpoint antibody receptor modified ARMed CAR T circumvents the suppressive immunome in GBM.

Introduction: Glioblastoma (GBM) remains a deadly cancer with non-curative upfront treatment of radiation, resection, and chemotherapy. Not only has the standard of care for GBM patients not improved significantly over the past decade, life expectancy is less than 18 months, with no standard second-line therapy. We previously developed a 2 generation 4-1BB co-stimulated chimeric antigen receptor (CAR) targeting tumor-specific variant of the epidermal growth factor receptor (EGFRvIII) for treating patients with GBM.

The Continuum of Prevention and Heart Failure in Cardiovascular Medicine: A Joint Scientific Statement from the Heart Failure Society of America and The American Society for Preventive Cardiology.

Heart disease is the leading cause of death worldwide, with heart failure (HF) recognized as its most severe and debilitating manifestation. Though remarkable advancements have led to the establishment of life-saving and quality-of-life-enhancing medical and device-based therapies for HF, HF-related mortality trends have increased over the past decade. To combat this worldwide epidemic, care must evolve so that preventative recommendations are not siloed from HF management.

Barriers, facilitators, and best practices for successful vaping prevention campaigns for sexual and gender minority youth.

Background: Sexual and gender minority youth (SGMY) vape at higher rates than their heterosexual and/or cisgender peers. SGMY prefer SGM-specific anti-tobacco messaging; however, there have been no vaping prevention campaigns designed for SGMY.

Purpose: Using the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, we sought to explore specific barriers, facilitators, and best practices for health promotion for SGMY that will inform future vaping prevention campaigns.

Mitochondrial clone tracing within spatially intact human tissues.

Understanding tissue development and intra-tissue evolution requires the ability to trace clones in intact tissues coupled with high-plex molecular profiling preserving spatial context. However, current lineage tracing tools are incompatible with spatial omics. Here, we present SUMMIT (Spatially Unveiling Mitochondrial Mutations In Tissues), a spatially-resolved lineage tracing technology that integrates gene expression profiling with mitochondrial mutation-based clone identification.

Exploration of possible association of pathogenic variants with central nervous system cancers in an institutional cohort.

(OMIM: 605882), associated with hereditary ovarian cancer, has recently been described in association with central nervous system (CNS) tumours. Institutional germline database review identified 43 families with pathogenic germline variants (PGVs); 7 families (16.3%) reported 8 CNS tumours.

Implementation of and Testing in Patients With GI Cancer: A Prospective, Nonrandomized Clinical Trial.

Purpose: To determine the feasibility and effectiveness of implementing pretreatment testing in patients with gastrointestinal cancer and its impact compared with a biobank population.

Materials And Methods: A prospective, nonrandomized implementation trial of pretreatment testing with preemptive dose reduction was conducted in patients initiating treatment with a fluoropyrimidine (FP, [fluorouracil or capecitabine]) or irinotecan. The primary end point was feasibility, defined as proportion of results available prior to cycle 1 of treatment.

One Size Does Not Fit All: Mediating Effects of Perceived Character Similarity in Tailored Health Messages for Sexual and Gender Minority Young Adults.

This research examines how gender expressions in health messages influence perceived message effectiveness (PME) for sexual and gender minority (SGM) young adults through perceived character similarity. In an online experiment, 1,113 SGM young adults were randomly assigned to view six anti-smoking messages portraying one of four gender expressions: feminine, masculine, gender expansive, or multiple gender. Findings indicated that messages with multiple gender expressions increased perceived character similarity among SGM young adults compared to messages showing masculine expressions; perceived character similarity mediated the relationship between message exposure and PME.