Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19

IMPORTANCE: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking. OBJECTIVE: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer. DESIGN, SETTING, AND PARTICIPANTS: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022. EXPOSURE: Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19. MAIN OUTCOMES AND MEASURES: Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up. RESULTS: Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13). CONCLUSIONS AND RELEVANCE: In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19-related thromboembolism in patients with cancer

Squamous cell carcinoma in congenital ichthyosis with deafness and keratitis. A case report and review of the literature.

The first case of invasive squamous cell carcinoma (SCC) arising in the skin of a patient afflicted with keratitis, ichthyosis, and deafness (KID) syndrome is reported. A 35-year-old man, diagnosed as having KID syndrome in early childhood, developed bilateral fungating lesions on his feet. The entire left foot became involved with a multinodular fungating mass which proved to harbor a SCC, necessitating a left below-knee amputation. Although rare, KID syndrome can be associated with SCC of the skin

Elevated ras oncogene expression correlates with lymph node metastases in breast cancer patients.

The protein product of the ras cellular oncogene(s) (p21) was assayed in primary breast carcinomas from two groups of patients who had different axillary lymph node status. Using an immunohistochemical assay, the intensity and percent of neoplastic cells demonstrating ras p21 antigen staining were significantly higher in the primary tumors from patients with lymph nodes positive (LN+) for malignancy (20 patients) compared with the lymph node negative (LNO) group (21 patients). The expression of p21 also correlated with tumor size. Age and estrogen receptor status did not influence p21 staining. The antigen expression of p21 was similar in intensity and distribution in the primary tumor and regional lymph node metastases. Enhanced expression of p21 in primary breast cancers that metastasize to regional nodes indicates that ras p21 may be a determinant of the malignant potential of breast cancer cells and may represent a new class of more biologically relevant tumor markers

Oncogene Mutations in Cancer and Dysplasia Associated with Inflammatory Bowel Disease

Chronic inflammatory bowel disease (IBO) predisposes affected individuals to the development of invasive colon cancer. Increased cancer risk has been seen in ulcerative colitis and Crohn's disease in Western societies as well as in schistosomal colitis in China. In this study it was found that the frequency of the 12th codon of c-Ki-ras, as well as the specific amino acid substitutions, were similar in sporadic colon cancers, cancers associated with ulcerative colitis in the United States, and colon cancers found in patients with schistosomal colitis in Jiangsu province in China. Further, activating mutations of codon 12 of e-Ki-ras were found in high grade dysplastic lesions in chronic ulcerative colitis. The latter finding indicates that some dysplasias are clonal proliferative lesions with genetic characteristics associated with invasive cancer

ras p21 expression in the progression of breast cancer.

The differential expression of the ras oncogene product p21 in the primary tumor, regional nodes, and distant metastatic sites in patients with disseminated breast cancer was examined to define the biologic and clinical significance of the ras oncogene in the progression of breast cancer. The avidin-biotin peroxidase complex method was used on formalin-fixed, paraffin-embedded tissues from 16 patients with metastatic disease. The primary antibody used in this protocol was RAP-5, an anti-p21 murine monoclonal IgG2a. p21 antigen staining was similar in the primary tumor and regional nodes from the same patient (P less than 0.05), but the staining of distant metastases was more variable. Expression of ras p21 was consistently increased in invasive components of the primary tumor as compared with intraductal tumor. In addition, a high level of p21 expression was seen in tumor emboli in lymphatics and blood vessels as compared with contiguous tumor in parenchymal tissue. Although p21 staining is present in aggressive primary breast cancers and most metastatic sites, our findings indicate that markedly enhanced p21 expression is associated with the earlier stages (invasion and dissemination) of aggressive breast cancers