Colorectal cancer (CRC) is one of the most lethal malignancies. The extreme heterogeneity in survival rate is driving the need for new prognostic biomarkers. Human endogenous retroviruses (hERVs) have been suggested to influence tumor progression, oncogenesis and elicit an immune response. We examined multiple next-generation sequencing (NGS)-derived biomarkers in 114 CRC patients with paired whole-exome and whole-transcriptome sequencing (WES and WTS, respectively). First, we demonstrate that the median expression of hERVs can serve as a potential biomarker for prognosis, relapse, and resistance to chemotherapy in stage II and III CRC. We show that hERV expression and CD8+ tumor-infiltrating T-lymphocytes (TILs) synergistically stratify overall and relapse-free survival (OS and RFS): the median OS of the CD8-/hERV+ subgroup was 29.8 months compared with 37.5 months for other subgroups (HR = 4.4, log-rank P < 0.001). Combing NGS-based biomarkers (hERV/CD8 status) with clinicopathological factors provided a better prediction of patient survival compared to clinicopathological factors alone. Moreover, we explored the association between genomic and transcriptomic features of tumors with high hERV expression and establish this subtype as distinct from previously described consensus molecular subtypes of CRC. Overall, our results underscore a previously unknown role for hERVs in leading to a more aggressive subtype of CRC.

/pdf/hervs-establish-a-distinct-molecular-subtype-in-stage-ii-iii-1juh92fwns.pdf

HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome.

Incremental delays in time to treatment initiation (TTI) have been shown to cause a proportional, increased independent risk of disease-specific mortality for breast cancer, colorectal cancer (CRC), head and neck cancer (HNC), non-small-cell lung cancer (NSCLC), and pancreatic cancer. Studies suggest that delays are associated with racial and socioeconomic disparities. We evaluated associations between patient factors and TTI to identify those associated with delay.This is a retrospective cohort study at an urban community-based academic center of patients diagnosed with or referred for curative-intent treatment of breast cancer, CRC, HNC, NSCLC, and pancreatic cancer from January 2019 to December 2021. Variables of interest included Charlson Comorbidity Index (CCI) score, insurance type, language preference, and inpatient admission 30 days before diagnosis. Factors associated with TTI delay, defined as TTI ≥ 30 days, were assessed using multivariable logistic regression.Among 2,543 patients (69% female), the mean age was 63.4 years and the median TTI was 25 days (IQR, 6-44). Within multivariable models, patients treated as outpatient and not admitted 30 days before diagnosis experienced statistically significant greater delay for CRC (odds ratio [OR], 2.82; 95% CI, 1.71 to 4.66) and NSCLC (OR, 2.11; 95% CI, 1.31 to 3.39). Higher CCI score was associated with delay for HNC (OR, 2.63; 95% CI, 1.04 to 6.66) and NSCLC (OR, 1.75; 95% CI, 1.14 to 2.71). For breast cancer, uninsured and Spanish-speaking patients (OR, 1.79; 95% CI, 1.21 to 2.67) experienced increased TTI.Care coordination/compliance (eg, inpatient 30 days before diagnosis), clinical (eg, medical comorbidities), and socioeconomic (eg, uninsured status) predictors for delayed TTI were identified and may inform delay minimizing interventions. Our data support evidence that TTI delays are associated with demographic and socioeconomic disparities. Existing disparities are likely exacerbated by delays that disproportionately affect patients with care coordination/compliance issues, multiple comorbidities, and lower socioeconomic status. 

Predictive Factors for Cancer Treatment Delay in a Racially Diverse and Socioeconomically Disadvantaged Urban Population

Background:Chemotherapy is an established treatment for stage III colon cancer cases. Older age is known to be associated with less chemotherapy use in these patients, but there might be other rele...

https://journals.sagepub.com/doi/pdf/10.1177/1758835920986520

The association of comorbidities with administration of adjuvant chemotherapy in stage III colon cancer patients: a systematic review and meta-analysis.

Modification to systemic anticancer therapy at the start of the COVID-19 pandemic and its overall impact on survival outcomes in patients with colorectal cancer

Modification to Systemic Anticancer Therapy at the Start of the COVID-19 Pandemic and its Overall Impact on Survival Outcomes in Patients with Colorectal Cancer

Introduction For stage III colon cancer (CC), surgery followed by chemotherapy is the main curative approach, although optimum times between diagnosis and surgery, and surgery and chemotherapy, have not been established. Materials and methods We analysed a population-based sample of 1912 stage III CC cases diagnosed in eight European countries in 2009–2013 aiming to estimate: (i) odds of receiving postoperative chemotherapy, overall and within eight weeks of surgery; (ii) risks of death/relapse, according to treatment, Charlson Comorbidity Index, time from diagnosis to surgery for emergency and elective cases, and time from surgery to chemotherapy; and (iii) time-trends in chemotherapy use. Results Overall, 97% of cases received surgery and 65% postoperative chemotherapy, with 71% of these receiving chemotherapy within eight weeks of surgery. Risks of death and relapse were higher for cases starting chemotherapy with delay, but better than for cases not given chemotherapy. Fewer patients with high comorbidities received chemotherapy than those with low (P  Conclusions Our data indicate that promptly-administered postoperative chemotherapy maximizes its benefit, and that careful assessment of comorbidities is important before treatment. The survival benefit associated with slightly delayed elective surgery deserves further investigation.

Comorbidities, timing of treatments, and chemotherapy use influence outcomes in stage III colon cancer: A population-based European study

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Comorbidities, timing of treatments, and chemotherapy use influence outcomes in stage III colon cancer: A population-based European study