Population Science and Cancer Control

Blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis

Amit Singal, M.D., and an inter-programmatic team of investigators, including Yujin Hoshida, M.D., Ph.D., compared biomarkers predictive of liver cancer risk and incidence among patients with cirrhosis. They identified a serum protein-based biomarker (PLSec) that stratifies patients into high and low risk for developing liver cancer and tracks changes in risk over time, such as reductions after hepatitis C treatment. For early tumor detection, Singal’s team compared a multitarget blood test (mt-HBT) with ultrasound-based surveillance and found mt-HBT detected more HCC cases than no surveillance, ultrasound alone, or ultrasound plus serum alpha-fetoprotein. Specifically, mt-HBT detected 45% of HCCs compared to 38% by ultrasound alone, representing 1,680 additional early-stage cases detected per 100,000 patients. Compared to ultrasound plus AFP, mt-HBT detected 350 more cases, translating to an additional 5,720 and 1,000 life years gained, respectively. 

Molecular signatures of long-term hepatocellular carcinoma risk in non-alcoholic fatty liver disease

For early tumor detection, Amit Singal’s, M.D., team compared a multitarget blood test (mt-HBT) with ultrasound-based surveillance and found mt-HBT detected more HCC cases than no surveillance, ultrasound alone, or ultrasound plus serum alpha-fetoprotein. Specifically, mt-HBT detected 45% of HCCs compared to 38% by ultrasound alone, representing 1,680 additional early-stage cases detected per 100,000 patients. Compared to ultrasound plus AFP, mt-HBT detected 350 more cases, translating to an additional 5,720 and 1,000 life years gained, respectively.  

Program discoveries from analysis of surveillance, epidemiology, and end results (SEER) program data have led to wider inclusion in clinical trials

Sandi Pruitt, Ph.D., M.P.H., and David Gerber, M.D., continue paradigm-shifting and policy-impacting work linking Surveillance, Epidemiology, and End Results (SEER) Medicare data to prevalence and outcomes of clinical trial enrollees with both prior and new cancer diagnoses. Prior cancer diagnosis has historically triggered exclusion from clinical trials, and the outcome and long-term care needs of these patients may be different from patients without a prior cancer diagnosis. Among 112,769 CRC patients >66 years of age, SEER data showed 14% had a previous cancer. Those with previous cancer had worse overall survival, but improved CRC-specific survival. Further those with a previous melanoma and stage IV CRC had equivalent survival to those without previous cancer. In 2023, the team published findings from an expanded dataset with 10 years of linked SEER-Medicare data across multiple cancers, showing a ~15% increase in number of survivors diagnosed with a new cancer over six years, as well as some disparities in second diagnoses by race and ethnicity. Based on these findings, the FDA now advises patients with prior or concurrent malignancies whose natural history or treatment does not have potential to interfere with the safety or efficacy assessment of the investigational drug should generally be eligible for enrollment in clinical trials.