Nomograms predict risk for early death in HCC, may guide ‘individualized treatment’
Internally validated nomograms predicted the probability of early death and identified risk factors among patients with advanced hepatocellular carcinoma, according to research published in BMC Gastroenterology.
“Studies have shown that the survival rates among patients with advanced HCC at 1, 2 and 3 years were 29%, 16% and 8%, and the median survival time was 5.3 months, indicating that advanced HCC patients were prone to early death,” Haidong Zhang, of the medical school at Southeast University in Nanjing, China, and colleagues wrote. “Therefore, early identification of risk factors for early death of advanced HCC patients and assessment of the incidence of early death will not only help clinicians discern high-risk patients in time, but also be conducive to reducing the pain and economic burden of patients.”

Seeking to explore the risk factors for early death ( 3 months of diagnosis) in patients with advanced HCC and develop nomograms to guide care, Zhang and colleagues evaluated 6,603 patients from the Surveillance, Epidemiology and End Results (SEER) database. They stratified patients according to the latest American Joint Commission on Cancer staging, defining patients with stage IVA HCC (21%) as those with regional lymph node metastasis but without distant metastasis and patients with stage IVB HCC (79%) as those with distant metastasis with or without lymph node metastasis.
According to study results, 44.6% of patients with stage IVA HCC experienced early death and 62.8% of patients with stage IVB HCC experienced early death.
For patients with stage IVA HCC, univariable and multivariable logistic regression yielded nine risk factors for early death, including:
- age (41-60 years: OR = 4.097; 95% 1.158-17.179; 61-80 years: OR = 4.444; 95% CI, 1.259-18.591; and > 80 years: OR = 2.675; 95% CI, 0.7-11.897)
- tumor size (21-50 mm: OR = 1.642; 95% CI, 0.746-3.880; 51-100 mm: OR = 2.571; 95% CI, 1.173-6.054; >100 mm: OR = 5.521; 95% CI, 2.443-13.37; and unknown: OR = 4.376; 95% CI, 1.897-10.795)
- histological grade (Grade 1-2: OR = 1.754; 95% CI, 1.079-2.869) and Grade 3-4/unknown: OR = 0.826; 95% CI, 0.59-1.156)
- alpha-fetoprotein ([AFP] positive: OR = 1.796; 95% CI, 1.191-2.728) and unknown: OR = 1.387; 95% CI, 0.844-2.289)
- Fibrosis score (Ishak 0-4: OR = 2.528; 95% CI, 1.174-5.650 and Ishak 5-6: OR = 2.043; 95% CI, 0.993-4.369)
- T stage (T 3-4: OR = 2.061; 95% CI, 1.501-2.838 and TX: OR = 1.714; 95% CI, 0.977-3.022)
- surgery (local tumor destruction: OR = 0.187; 95% CI, 0.053-0.502; wedge resection: OR = 0.083; 95% CI, 0.012-0.332; and lobectomy: OR = 0.02; 95% CI, 0.001-0.108)
- radiotherapy (OR = 0.08; 95% CI, 0.041-0.145)
- chemotherapy (OR = 0.144; 0.109-0.19)
Ten risk factors for early death among patients with stage IVB HCC include:
- age (OR = 1.728; 95% CI, 1.09-2.740; OR = 1.804; 95% CI, 1.137-2.864; and OR = 1.44; 95% CI, 0.864-2.403; respectively)
- histological grade (OR = 2.178; 95% CI, 1.703-2.792 and OR = 1.4; 95% CI, 1.176-1.666)
- AFP (OR = 1.462; 95% CI, 1.194-1.791 and OR = 1.24; 95% CI, 0.984-1.563)
- T stage (OR = 1.363; 95% CI, 1.171-1.588 and OR = 1.249; 95% CI 1.03-1.516)
- N stage (N1: OR = 1.21; 95% CI, 1.029-1.426 and NX: OR = 0.994; 95% CI, 0.821-1.206)
- bone metastasis (yes: OR = 1.239; 95% CI, 1.05-1.463 and unknown: OR = 0.715; 95% CI, 0.487-1.057)
- lung metastasis (yes: OR = 2.195; 95% CI, 1.901-2.537 and unknown: OR = 1.214; 95% CI, 0.839-1.763)
- surgery (OR = 0.139; 95% CI, 0.067-0.265; OR = 0.204; 95% CI, 0.089-0.441; OR = 0.077; 95% CI, 0.032-0.165; and OR = 0.649; 95% CI, 0.141-2.597)
- radiotherapy (OR = 0.342; 95% CI, 0.281-0.415)
- chemotherapy OR = 0.163; 95% CI, 0.142-0.187)
Researchers reported the nomographs had significant “predictive ability” and “high accuracy,” with area under the curve of 0.83 (95% CI, 0.809-0.851) among patients with stage IVA HCC and 0.789 (95% CI, 0.768-0.81) among patients with stage IVB HCC.
“Based on the large sample size provided by the SEER database, the risk factors for early death of patients with advanced HCC were identified and nomograms were developed,” Zhang and colleagues concluded. “The nomograms may help oncologists and clinicians identify risk factors and probability of early death more quickly and accurately, so as to allow for more precise individualized treatment plans to be formulated, thereby improving the patients’ survival probability and quality of life.”