Host Nuclear Genome Copy Number Variations Identify High-Risk Anal Precancers in People Living With HIV.

BACKGROUND: People living with HIV (PLWH) have substantially increased incidence of anal precancer and cancer. There are very little data regarding genomic disturbances in anal precancers among PLWH. In this study, specific chromosomal variants were identified in anal squamous intraepithelial lesions. METHODS: Overall, 63 anal biopsy specimens (27 low-grade intraepithelial lesions [LSIL] and 36 high-grade intraepithelial lesions [HSIL]) were collected from PLWH obtained as part of anal cancer screening in our NYC-based health system. Data on patient demographics, anal cytological, and high-risk human papillomavirus (HR-HPV) diagnoses were collected. Specimens were tested for a panel of chromosomal alterations associated with HPV-induced oncogenesis using fluorescence in situ hybridization, and analyses compared the associations of these alterations with clinical characteristics. RESULTS: Gains of 3q26, 5p15, 20q13, and cen7 were detected in 42%, 31%, 31%, and 19% of HSIL compared with 7%, 0%, 4%, and 0% of LSIL, respectively. If at least 1 abnormality was observed, 89% had a 3q26 gain. In lesions with 5p15 gains, 20q13 gains co-occurred in 91% of cases, while cen7 gain only co-occurred with the other 3 alterations. The sensitivity and specificity of any alteration to predict HSIL were 47% (95% CI: 30%-65%) and 93% (95% CI: 76%-99%), respectively. CONCLUSIONS: Genomic alterations seen in HPV-associated cancers may help distinguish anal LSIL from HSIL. 3q26 amplification may be an early component of anal carcinogenesis, preceding 5p16, 20q13, and/or chr7. IMPACT: Insights into potential genomic biomarkers for discriminating high-risk anal precancers are shared.

Care disruptions among patients with lung cancer: A COVID-19 and cancer outcomes study.

INTRODUCTION: Patients with lung cancer (LC) are susceptible to severe outcomes from COVID-19. This study evaluated disruption to care of patients with LC during the COVID-19 pandemic. METHODS: The COVID-19 and Cancer Outcomes Study (CCOS) is a prospective cohort study comprised of patients with a current or past history of hematological or solid malignancies with outpatient visits between March 2 and March 6, 2020, at two academic cancer centers in the Northeastern United States (US). Data was collected for the three months prior to the index week (baseline period) and the following three months (pandemic period). RESULTS: 313 of 2365 patients had LC, 1578 had other solid tumors, and 474 had hematological malignancies. Patients with LC were not at increased risk of COVID-19 diagnosis compared to patients with other solid or hematological malignancies. When comparing data from the pandemic period to the baseline period, patients with LC were more likely to have a decrease in in-person visits compared to patients with other solid tumors (aOR 1.94; 95% CI, 1.46-2.58), but without an increase in telehealth visits (aOR 1.13; 95% CI 0.85-1.50). Patients with LC were more likely to experience pandemic-related treatment delays than patients with other solid tumors (aOR 1.80; 95% CI 1.13-2.80) and were more likely to experience imaging/diagnostic procedure delays than patients with other solid tumors (aOR 2.59; 95% CI, 1.46-4.47) and hematological malignancies (aOR 2.01; 95% CI, 1.02-3.93). Among patients on systemic therapy, patients with LC were also at increased risk for decreased in-person visits and increased treatment delays compared to those with other solid tumors. DISCUSSION: Patients with LC experienced increased cancer care disruption compared to patients with other malignancies during the early phase of the COVID-19 pandemic. Focused efforts to ensure continuity of care for this patient population are warranted.

Cost-Effectiveness and Clinical Effectiveness of the Risk Factor Management Clinic in Atrial Fibrillation: The CENT Study.

BACKGROUND: Atrial fibrillation (AF) imposes a substantial cost burden on the healthcare system. Weight and risk factor management (RFM) reduces AF burden and improves the outcomes of AF ablation. OBJECTIVES: This study sought to evaluate the cost and clinical effectiveness of integrating RFM into the overall management of AF. METHODS: Of 1,415 consecutive patients with symptomatic AF, 825 patients had body mass index ≥27 kg/m2. After screening for exclusion criteria, the final cohort comprised 355 patients: 208 patients who opted for RFM and 147 control subjects and were followed by 3 to 6 monthly clinic review, 7-day Holter monitoring, and AF Symptom Score. A decision analytical model calculated the incremental cost-effectiveness ratios of cost per unit of global well-being gained and unit of AF burden reduced. RESULTS: There were no differences in baseline characteristics or follow-up duration (p = NS). Arrhythmia-free survival was better in the RFM compared with control subjects (Kaplan-Meier: 79% vs. 44%; p < 0.001). At follow-up, RFM group had less unplanned specialist visits (0.19 ± 0.40 vs. 1.94 ± 2.00; p < 0.001), hospitalizations (0.74 ± 1.3 vs. 1.05 ± 1.60; p = 0.03), cardioversions (0.89 ± 1.50 vs. 1.51 ± 2.30; p = 0.002), emergency presentations (0.18 ± 0.50 vs. 0.76 ± 1.20; p < 0.001), and ablation procedures (0.60 ± 0.69 vs. 0.72 ± 0.86; p = 0.03). Antihypertensive (0.53 ± 0.70 vs. 0.78 ± 0.60; p = 0.04) and antiarrhythmic (0.26 ± 0.50 vs. 0.91 ± 0.60; p = 0.003) use declined in RFM. The RFM group had an increase of 0.1930 quality-adjusted life years and a cost saving of $12,094 (incremental cost-effectiveness ratios of $62,653 saved per quality-adjusted life years gained). CONCLUSIONS: A structured physician-directed RFM program is clinically effective and cost saving.

Human monoclonal antibodies to the insulin-like growth factor 1 receptor inhibit receptor activation and tumor growth in preclinical studies.

INTRODUCTION: The insulin-like growth factor type 1 (IGF-1) receptor contributes importantly to transformation and survival of tumor cells both in vitro and in vivo, and selective antagonists of the IGF-1 receptor (IGF-1R) activity represent an attractive experimental approach for human cancer therapy. METHODS: Using a phage display library, we identified several high-affinity fully human monoclonal antibodies with inhibitory activity against both human and rodent IGF.1Rs. RESULTS: These candidate therapeutic antibodies recognized several distinct epitopes and effectively blocked ligand-mediated receptor signal transduction and cellular proliferation in vitro. They also induced IGF-1R downregulation and catabolism following antibody-mediated endocytosis. These antibodies exhibited activity against human, primate, and rodent IGF-1Rs, and dose-dependently inhibited the growth of established human tumors in nude mice. CONCLUSION: These fully human antibodies therefore have the potential to provide an effective anti-tumor biological therapy in the human clinical setting.