Fong, Yuman

Abstract Oncolytic viruses (OV) are live viruses that can selectively replicate in cancer cells. We have engineered an OV (CF33) to make it cancer-selective through the deletion of its J2R (thymidine kinase) gene. In addition, this virus has been armed with a reporter gene, human sodium iodide symporter (hNIS), to facilitate noninvasive imaging of tumors using PET. In this study, we evaluated the oncolytic properties of the virus (CF33-hNIS) in liver cancer model, and its usefulness in tumor imaging. The virus was found to efficiently kill liver cancer cells and the virus-mediated cell death exhibited characteristics of immunogenic death based on the analysis of 3 damage-associated molecular patterns: calreticulin, ATP, and high mobility group box-1. Furthermore, local or systemic administration of a single dose of the virus showed antitumor efficacy against a liver cancer xenograft model in mice and significantly increased survival of treated mice. Finally, PET scanning was performed following injection of the radioisotope I-124, for imaging of tumors, and a single dose of virus as low as 1E03 pfu, administered intra-tumorally or intravenously, allowed for PET imaging of tumors. In conclusion, CF33-hNIS is safe and effective in controlling human tumor xenografts in nude mice, and it also facilitates noninvasive imaging of tumors.

AbstractBackgroundThe feasibility of remote perioperative telemonitoring of patient‐generated physiologic health data and patient‐reported outcomes in a high risk complex general and urologic oncology surgery population is evaluated.MethodsComplex general surgical/urologic oncology patients wore a pedometer, completed ePROs (electronic patient‐reported outcome surveys) and record their vitals (weight, pulse, pulse oximetry, blood pressure, and temperature) via a telehealth app platform. Feasibility (% adherence) was assessed as the primary outcome measure.ResultsTwenty‐one patients with a median age 58 (32−82) years were included. The readmission rate was 33% and the incidence of ≥Grade 3a morbidity was 24%. Adherence to vital sign and ePRO measurements was 95% before surgery, 91% at discharge, and 82%, 68%, and 64% at postdischarge d2, 7, 14, and 30, respectively. There was significant worsening of mobility, self‐care and usual daily activity at postdischarge d2 compared to preoperative baseline (p < 0.05). Median daily preoperative steps taken by patients with <Grade 3a versus ≥Grade 3a postoperative morbidity was 6062 versus 4166 (p < 0.05). Of those interviewed, 87% (13/15) viewed vital sign devices as helpful in recovery.ConclusionsTelemonitoring is feasible in a general surgical and urologic oncology setting. Future studies will ascertain optimal patient selection, duration, and extent of perioperative monitoring.

BACKGROUND: Peritoneal metastases arise in patients with a variety of primary cancers, and are associated with a poor prognosis. Systemic chemotherapy is the mainstay of treatment; however, the morbidity is considerable and the survival benefit is modest. Cytoreductive surgery and heated intraperitoneal chemotherapy is a potentially curative treatment available to a minority of patients; however, most develop recurrent disease. A novel palliative treatment for peritoneal metastases, pressurized intraperitoneal aerosol chemotherapy, has recently been introduced. Pressurized intraperitoneal aerosol chemotherapy utilizes an aerosol of chemotherapy in carbon dioxide gas. It is instilled into the abdomen under pressure via laparoscopic ports. No cytoreduction is performed. Pressurized intraperitoneal aerosol chemotherapy can be repeated at 6-week intervals. Oxaliplatin or cis-platinum and doxorubicin have been used to date. OBJECTIVE: This study aims to systematically review and evaluate the method, and the preclinical and early clinical results of pressurized intraperitoneal aerosol chemotherapy. DATA SOURCES: Medline and the Cochrane Library were the data sources for the study. STUDY SELECTION: Peer-reviewed series of greater than 10 patients, with sufficient patient data, through April 2019, were selected. INTERVENTION: Patients with peritoneal metastases underwent pressurized intraperitoneal aerosol chemotherapy. MAIN OUTCOME MEASURES: Patient dropout, histologic tumor response, adverse events, and 30-day mortality were the primary outcomes measured. RESULTS: A total of 921 patients with peritoneal metastases were brought to the operating room for pressurized intraperitoneal aerosol chemotherapy. The number of pressurized intraperitoneal aerosol chemotherapy treatments administered was as follows: 1 treatment, 862 (94%); 2 treatments, 645 (70%); and 3 treatments, 390 patients (42%). Initial laparoscopic access was not possible in 59 patients (6.4%). Common Terminology Criteria for Adverse Events grade 3 or higher were noted in 13.7% of the patients who, collectively, underwent a total of 2116 treatments. The 30-day mortality was 2.4% (22/921). LIMITATIONS: This study was limited by the heterogeneity of reported data and primary tumor types and by the lack of long-term survival data. CONCLUSIONS: Early clinical results are encouraging, but tumor-specific, prospective, randomized trials are needed to compare pressurized intraperitoneal aerosol chemotherapy to systemic chemotherapy. This method has yet to be introduced to the United States. It is another therapeutic option for patients with peritoneal metastases and will broaden the patient base for future clinical trials.

Hepatocelluar carcinoma (HCC) is the most common primary malignancy of the liver in adults and the third most common cause of cancer death worldwide. The incidence of HCC in the United States is rising steadily because of the prevalence of hepatitis C viral infection and other causes of hepatic cirrhosis. The majority of patients have underlying hepatic dysfunction, which complicates patient management and the search for safe and effective therapies. The Clinical Trials Planning Meeting (CTPM) in HCC was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to identify the key knowledge gaps in HCC and define clinical research priorities. The CTPM structured its review according to current evidence-based treatment modalities in HCC and prioritized the recommendations on the basis of the patient populations representing the greatest unmet medical need.