Background Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms of tumor and stroma cell contributions to pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples and analyze multiple independent external cohorts for a total of 487,829 single cells enabling high-resolution depiction of the cellular diversity and heterogeneity within the tumor and microenvironmental cells. Results Tumor cells recapitulate individual CMS subgroups yet exhibit significant intratumoral CMS heterogeneity. Both CMS1 microsatellite instability (MSI-H) CRCs and microsatellite stable (MSS) CRC demonstrate similar pathway activations at the tumor epithelial level. However, CD8+ cytotoxic T cell phenotype infiltration in MSI-H CRCs may explain why these tumors respond to immune checkpoint inhibitors. Cellular transcriptomic profiles in CRC exist in a tumor immune stromal continuum in contrast to discrete subtypes proposed by studies utilizing bulk transcriptomics. We note a dichotomy in tumor microenvironments across CMS subgroups exists by which patients with high cancer-associated fibroblasts (CAFs) and C1Q+TAM content exhibit poor outcomes, providing a higher level of personalization and precision than would distinct subtypes. Additionally, we discover CAF subtypes known to be associated with immunotherapy resistance. Conclusions Distinct CAFs and C1Q+ TAMs are sufficient to explain CMS predictive ability and a simpler signature based on these cellular phenotypes could stratify CRC patient prognosis with greater precision. Therapeutically targeting specific CAF subtypes and C1Q + TAMs may promote immunotherapy responses in CRC patients.

Pancreatic cancer is a challenging disease with a low 5-year survival rate. There are areas for improvement in the tools used for screening, diagnosis, prognosis, treatment selection, and assessing treatment response. Liquid biopsy, particularly cell free DNA liquid biopsy, has shown promise as an adjunct to our standard care for pancreatic cancer patients, but has not yet been universally adopted into regular use by clinicians. In this publication, we aim to review cfDNA liquid biopsy in pancreatic cancer with an emphasis on current techniques, clinical utility, and areas of active investigation. We feel that researchers and clinicians alike should be familiar with this exciting modality as it gains increasing importance in the care of cancer patients.

BACKGROUND:A new bibliometric index called the disruption score was recently proposed to identify innovative and paradigm-changing publications. OBJECTIVE:The goal was to apply the disruption score to the colorectal surgery literature to provide the community with a repository of important research articles.DESIGN: This study is a bibliometric analysis.

Background Despite improvements, disparities in breast cancer care have led to an inequitable distribution of treatment delays and worse outcomes among patients with breast cancer. This study aimed to quantify the contribution of mediators that may explain racial/ethnic disparities in breast cancer treatment delays. Patients and Methods We conducted a retrospective analysis of patients from the National Cancer Database with stage I–III breast cancer who underwent surgical resection. Mediation analyses estimated the extent to which racial/ethnic disparities in the distribution of patient characteristics account for racial/ethnic disparities in delayed treatment. Results Of the 1,349,715 patients with breast cancer included, 10%, 5%, and 4% were Black, Hispanic, and other non-white race/ethnicity, respectively. Multivariable models showed that patients in these racial/ethnic groups had 73%, 81%, and 24% increased odds of having a treatment delay relative to white patients. Mediation analyses suggested that 15%, 19%, and 15% of the treatment delays among Black, Hispanic, and other non-white race/ethnicity patients, respectively, are explained by disparities in education, comorbidities, insurance, and facility type. Therefore, if these mediators had been distributed equally among all races/ethnicities, a reduction of 15–19% in the delayed treatment disparities experienced by minority patients would have been observed. Academic facility type was the factor that could yield the largest reduction in time to treatment disparities, contributing to 8–13% of racial/ethnic disparities. Conclusions Patients with breast cancer who identified as Black, Hispanic, and other non-white races/ethnicities are exposed to longer treatment delays relative to white patients. Efforts to equalize mediators could remove substantial portions of racial/ethnic disparities in delayed treatment.

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