A proactive financial navigation intervention in patients with newly diagnosed gastric and gastroesophageal junction adenocarcinoma.

PURPOSE: Many cancer patients and caregivers experience financial hardship, leading to poor outcomes. Gastric and gastroesophageal junction (GEJ) cancer patients are particularly at risk for financial hardship given the intensity of treatment. This pilot randomized study among gastric/GEJ cancer patients and caregivers tested a proactive financial navigation (FN) intervention to obtain a signal of efficacy to inform a larger, more rigorous randomized study. METHODS: We tested a 3-month proactive FN intervention among gastric/GEJ cancer patients and caregivers compared to usual care. Caregiver participation was optional. The primary endpoint was incidence of financial hardship, defined as follows: accrual of debt, income decline of ≥ 20%, or taking loans to pay for treatment. Data from participant surveys and documentation by partner organizations delivering the FN intervention was analyzed and outcomes were compared between study arms. RESULTS: Nineteen patients and 12 caregivers consented. Primary FN resources provided included insurance navigation, budget planning, and help with out-of-pocket medical expenses. Usual care patients were more likely to experience financial hardship (50% vs 40%) and declines in quality of life (37.5% vs 0%) compared to intervention patients. Caregivers in both arms reported increased financial stress and poorer quality of life over the study period. CONCLUSIONS: Proactive financial navigation has potentially positive impacts on financial hardship and quality of life for cancer patients and more large-scale randomized interventions should be conducted to rigorously explore the impact of similar interventions. Interventions that have the potential to lessen caregiver financial stress and burden need further exploration. TRIAL REGISTRATION: TRN: NCT03986502, June 14, 2019.

Quantification of circulating HBV RNA expressed from intrahepatic cccDNA in untreated and NUC treated patients with chronic hepatitis B.

OBJECTIVE: A convenient, reproducible biomarker of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) transcriptional activity is lacking. We measured circulating HBV RNA (cirB-RNA) in untreated and nucleos(t)ide analogues (NUC) treated chronic hepatitis B (CHB) patients to define its correlation with intrahepatic viral markers and HBV core-related antigen (HBcrAg). DESIGN: Paired liver biopsy and serum samples were collected from 122 untreated and 30 NUC-treated CHB patients. We measured cirB-RNA, HBV DNA, hepatitis B surface antigen (HBsAg), HBcrAg and alanine aminotransferase levels. cirB-RNA was quantified using an investigational HBV RNA assay for use on the cobas 6800 system. The test detects a region spanning the HBV canonical polyadenylation site. cccDNA and 3.5 kb RNA in liver tissue were assessed by quantitative PCR and droplet digital PCR. RESULTS: cirB-RNA was detectable in 100% of HBeAg(+) chronic hepatitis (CH), 57% and 14% of HBeAg(-) CH and chronic infection untreated patients and 47% of NUC-treated patients. cirB-RNA undetectability was associated with lower intrahepatic cccDNA transcriptional activity, as well as serum HBcrAg, but no significant differences in HBsAg, in both untreated and treated patients. In untreated HBeAg(-) patients, cirB-RNA correlated with intrahepatic 3.5 kb RNA and cccDNA transcriptional activity, serum HBV DNA and HBcrAg, but not with HBsAg or total cccDNA levels. Combined undetectability of both cirB-RNA and HBcrAg detection in untreated HBeAg(-) patients identified a subgroup with the lowest levels of intrahepatic transcriptionally active cccDNA. CONCLUSION: Our results support the usefulness of quantification of circulating HBV RNA expressed from cccDNA as an indicator of intrahepatic active viral reservoir in both untreated and NUC-treated CHB patients. TRIAL REGISTRATION NUMBER: NCT02602847.

Insertional activation of STAT3 and LCK by HIV-1 proviruses in T cell lymphomas.

Retroviruses cause cancers in animals by integrating in or near oncogenes. Although HIV-1 infection increases the risk of cancer, most of the risk is associated with immunodeficiency and coinfection by oncogenic virus (Epstein-Barr virus, Kaposi sarcoma herpesvirus, and human papillomavirus). HIV-1 proviruses integrated in some oncogenes cause clonal expansion of infected T cells in vivo; however, the infected cells are not transformed, and it is generally believed that HIV-1 does not cause cancer directly. We show that HIV-1 proviruses integrated in the first introns of signal transducer and activator of transcription 3 (STAT3) and lymphocyte-specific protein tyrosine kinase (LCK) can play an important role in the development of T cell lymphomas. The development of these cancers appears to be a multistep process involving additional nonviral mutations, which could help explain why T cell lymphomas are rare in persons with HIV-1 infection.