Clinical Characteristics, Treatment Patterns, and Outcomes of Patients With Locally Advanced/Metastatic Hepatocellular Carcinoma Treated at the Veterans Health Administration.

PURPOSE: This study retrospectively reviewed the outcomes of patients with advanced hepatocellular carcinoma (HCC) receiving atezolizumab with bevacizumab (A + B) therapy at the Veterans Health Administration (VHA). PATIENTS AND METHODS: Patients with advanced HCC who received first-line systemic therapy with A + B at the VHA between December 1, 2019, and March 1, 2022, were selected from electronic medical records (EMR) using ICD-9 and ICD-10 codes. Abstractors reviewed the EMR of the patients from their index date of A + B initiation until death or their last VHA visit, with the study period ending on January 31, 2023. The chi-square test was used to compare rates, and the Mann-Whitney test was used to compare medians. RESULTS: A total of 332 patients met the study criteria. The median age was 67 years; 99% were male, 63% were non-Hispanic Whites, 26% were Black, and 66% had an Eastern Cooperative Oncology Group performance status of ≥1. 84% had child Pugh score (CPS) class A, 16% had CPS classes B and C, 62% had a grade 2 albumin-bilirubin score, 56% had HCC caused by viral hepatitis, 80% had cirrhosis, and 67% had received prior local therapies. The 6-month progression-free survival (PFS) was 59%, while the 1-year PFS rate was 36%. Overall survival (OS) at 1-year was 52% in our study. CONCLUSION: In real world, despite having similar PFS as the phase III IMbrave 150 trial, our OS at 12 months was lower (52% vs. 67%) because our study included a higher proportion of elderly patients with moderate liver dysfunction and a 40% non-White. This study provided real-world outcomes that differed from the study population in a pivotal trial.

Late-stage diagnosis of carcinoid heart disease due to lack of access to health care.

Carcinoid syndrome (CS) is a unique constellation of symptoms caused by release of vasoactive substances from neuroendocrine tumors (Pandit et al., StatPearls, 2022). Neuroendocrine tumors are rare with an annual incidence of 2 in 100,000 people (Ram et al., 46:21-27, 2019). Up to 50% of patients with these tumors will develop carcinoid syndrome, which is characterized by symptoms caused by elevated levels of serotonin and most commonly include fatigue, flushing, wheezing, and non-specific gastrointestinal symptoms such as diarrhea and malabsorption (Pandit et al., StatPearls, 2022) (Fox et.al., 90:1224-1228, 2004). Over time, patients with carcinoid syndrome can develop carcinoid heart disease (CHD). CHD refers to the cardiac complications that occur when the vasoactive substances, such as serotonin, tachykinins, and prostaglandins, secreted from the carcinoid tumors. These complications most commonly include valvular abnormalities, but can also present as coronary artery damage, arrhythmias or direct myocardial injury (Ram et al., 46:21-27, 2019). While CHD is not typically an initial feature of carcinoid syndrome, it does eventually occur in up to 70% of patients with carcinoid tumors (Ram et al., 46:21-27, 2019) (Jin et.al., 146:65-73, 2021) (Macfie et.al., 224:665-669, 2022). CHD is associated with significant morbidity and mortality due to the risk of progressive heart failure (Bober et.al., 14:1179546820968101, 2020). In this case, we describe a 35-year-old Hispanic woman in South Texas with undiagnosed carcinoid syndrome for over 10 years that eventually progressed to severe CHD. In this patient's case, we emphasize how lack of access to healthcare resulted in delay of diagnosis, appropriate treatment, and worsened prognosis in this young patient.

Cyclophosphamide Use in Multiple Sclerosis: Levels Detected in Human Milk.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune inflammatory neurological disease of the central nervous system. It is the most common immune-mediated disorder, affecting >2 million people worldwide. Cyclophosphamide is an alkylating agent commonly used to treat both malignancies and immune-mediated inflammatory nonmalignant processes. At present, there are no data available on its use in breastfeeding mothers. CASE REPORT: In this study we report a 33-year-old mother who was suffering from MS. To treat her MS, stem cell transplantation protocol required preparation with multiple doses of cyclophosphamide. She had been exclusively breastfeeding for 6 months before undertaking this regimen. She voluntarily collected her milk samples at critical time points after the intravenous doses of 2.8 g cyclophosphamide for each of 4 days. Quantification of cyclophosphamide was determined using liquid chromatography coupled with tandem mass spectrometry. DISCUSSION: Low levels in milk were determined for cyclophosphamide as the area under the curve was 364.1 µg.hour/mL on day 1 and 113.9 µg.hour/mL on day 4. Maximum concentration of cyclophosphamide was observed on day 1 at 40.82 µg/mL, which peaked at 4 hours. For 24 hours, the levels gradually receded to minimum concentrations. The average relative infant dose (RID) for a period of 4 days varied from 4.7% at day 1 to 0.9% at day 4. CONCLUSIONS: Cyclophosphamide is transferred into breast milk in measurable quantities. This case report found RID of cyclophosphamide to be relatively low. However, great caution should be taken in counseling mothers regarding breastfeeding with this toxic drug.