Second Primary Malignancies in Patients With Hepatocellular Carcinoma: A Population-Based Analysis

Abstract

BackgroundSecond primary malignancy (SPM) is becoming a threat for the health of cancer survivors. However, data on the features and results of patients with hepatocellular carcinoma (HCC) with SPMs are scarce. This study aimed to explore the characteristics of HCC patients with SPMs and to screen HCC patients who are at a high risk of developing SPMs.MethodHCC patients diagnosed between 2000 and 2014 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. Eligible patients were divided into the only one primary malignancy and SPM groups. The Fine-Gray proportional subdistribution hazards model was used to explore the risk factors of developing SPMs, and a competing-risk model was established to predict the probability of developing SPMs for HCC patients after initial diagnosis. The calibration curves, concordance index (C-index), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram.ResultsA total of 40,314 HCC patients were identified, 1,593 (3.95%) of whom developed SPMs 2 months after the initial diagnosis with a maximum follow-up time of approximately 18 years. The 3-, 5-, and 10-year cumulative incidence of SPMs were 2.35%, 3.12%, and 4.51%, respectively. Age at initial diagnosis, extent of disease, tumor size, and treatment were identified as the independent risk factors of developing SPMs and integrated into the competing-risk nomogram. The C-index of the nomogram was 0.677 (95% confidence interval 0.676–0.678), and the calibration curves showed an excellent agreement between the nomogram prediction and the actual observations. Furthermore, DCA indicated that the nomogram had good net benefits in clinical scenarios.ConclusionsHCC survivors remain at a high risk of developing SPMs. The development of SPMs was associated with the clinical features and treatment strategies. A competing-risk nomogram was constructed to help surgeons identify the patients who are at a high risk of developing SPMs and contribute to the further management of SPMs.

Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients

“…Liver transplantation represents the best treatment choice for patients with acute or chronic liver failure and for a fraction of those with HCC ( 6 ); however, after successful liver transplantation, de novo malignancies (DNMs) and HCC recurrence are the most common causes of long-term morbidity and death ( 7 , 8 , 25 ). The need of identifying biological markers predictive of the risk to develop post-transplant malignancies is therefore clinically important.…”

“…HCC is the most common type of liver cancer, accounting for 75%–85% of cases ( 6 , 7 ), and is characterized by rapid progression, frequent metastasis, late diagnosis, high post-operative recurrence and poor prognosis ( 6 ). It has been reported that liver transplanted patients for HCC (LT-HCC) tended to be at higher risk of developing de novo malignancies (DNMs) compared to liver transplanted patients for other causes (LT-no-HCC) ( 7 ). Recently, an earlier onset of solid DNMs in LT-HCC compared to LT-no-HCC has been documented ( 8 ).…”