C-Reactive Protein Could Predict Survival in Patients With ICC Taking PD-1 Inhibitors

Measures of inflammation—and C-reactive protein (CRP), in particular—appear to be valuable prognostic tools for patients with intrahepatic cholangiocarcinoma (ICC) who are receiving anti-programmed cell death protein-1 (PD-1) therapy, according to a new study.

Anti-PD-1 immunotherapy has become a major focus of ICC therapy in recent years, but corresponding author Dandan Hu, MD, of Sun Yat-Sen University, in China, wrote along with colleagues that many patients will not respond to the therapy.

“[T]he efficacy of immunotherapy varies from person to person, based on results from completed studies of anti-PD-1 monotherapy in ICC, objective response rates (ORRs) ranged from 3% to 21.4%,” Hu and colleagues said.

Unfortunately, there is not yet a reliable way to predict which patients will respond to the treatment. Hu and colleagues wondered whether inflammation might be the answer.

“In established cancers, there is increasing evidence for the roles that local immune response and systemic inflammation have in progression of tumors and survival of patients with cancer,” the authors wrote.

They said inflammation scores have already been found to have prognostic value in patients with hepatocellular cholangiocarcinoma (HCC), but whether the predictive value might be similar in ICC has not yet been extensively investigated.

In a new study published in the Journal of Inflammation Research, Hu and colleagues sought to evaluate the links between inflammation and outcomes in patients with ICC treated with PD-1 inhibitors.

They recruited a total of 73 patients who were treated with PD-1 inhibitors between February 2019 and February 2021. The group was made up mostly of men (67.1%), and the median age was 57 years. Most patients (68.5%) had multiple tumors, about half of patients had macrovascular invasion (45.2%), and a majority had lymph node metastasis (65.8%). The median tumor size was 8.2 cm, but the largest was 21.5 cm.

The investigators collected a wide array of data about the patients, including demographic data and tumor characteristics. In addition, they scored patients using 10 representative inflammation-based prognostic tools, including CRP, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, and systemic immune inflammation index (SII).

Hu and colleagues found that all 10 of the inflammation-based prognostic scores were able to predict overall survival (OS), but they said CRP was the best predictor of OS in multivariate analysis (HR, 6.032; 95% CI, 2.467-14.752; P < .001). The area under the receiver operating characteristic curve for CRP consistently outperformed the other inflammation scores at 6 months through 24 months.

“CRP is an acute-phase protein and a well-accepted marker of cancer-induced systemic inflammation, a condition which is clinically often reflected in cancer symptoms such as weight loss, fatigue, and anorexia,” Hu and colleagues wrote. “Therefore, the CRP level links with the clinical manifestations and may associate with the clinicopathological features of patients.”

The investigators said their study had limitations, including the relatively small sample size and the retrospective nature of the study. They also noted that the underlying molecular mechanisms of inflammation in ICC are not well understood; they said a better understanding of such connections is necessary to fully understand why CRP appears to correlate with survival.

“Finally, CRP is a sensitive acute-phase protein, which could be affected by many factors, such as acute and chronic inflammation, undocumented infection, and trauma,” they added. “Therefore, serum CRP levels should be detected in the stable phase to avoid the interference of other potential factors.”

Still, Hu and colleagues concluded that their data suggest CRP can be a meaningful and relatively simple way to risk-stratify patients with ICC who are treated with anti-PD-1 therapies.

Reference

Yang Z, Zhang D, Zeng H et al. Inflammation-based scores predict responses to PD-1 inhibitor treatment in intrahepatic cholangiocarcinoma. J Inflamm Res. 2022;(15):5721-5731. doi:10.2147/jir.s385921