Clinical Features And Prognosis In Patients With Primary Hepatic Sarcomatoid Carcinoma

BackgroundPrimary liver cancer is a major health problem with more than 850,000 new cases annually worldwide.This neoplasm is currently the second leading cause of cancer-related death.Among all primary liver cancers,hepatocellular carcinoma(HCC)is the most common neoplasm,accounting for approximately 85%to 90%of cases.With the progress of medical diagnostic techniques such as immunohistochemistry and genetic testing,the pathological classification of primary liver cancer has become more precise.The abundance of treatment methods has greatly improved the prognosis of patients with liver cancer.However,there are still some rare pathological subtypes that lack reliable treatment regimens and have poor prognosis.Primary hepatic sarcomatoid carcinoma(PHSC)is a malignant liver tumor with both carcinomatous(either hepatocellular or cholangiocellular)and sarcomatoid spindle cell components.The pathological subtype accounts for 1.8%～3.9%of primary liver cancer.PHSC is rarely seen clinically.Many patients survive less than one year once diagnosed,most of articles on PHSC are only case reports,and most of the reported subjects are early operable patients.However,even after surgical resection is completed,the one-year survival rate of PHSC patients is only about 22%.In clinical practice,due to the high degree of malignancy and intense aggressiveness of PHSC,most patients have had distant metastasis at the time of pathological diagnosis and have lost the opportunity of performing radical resection.Meanwhile,the efficacy of traditional chemoradiotherapy,local therapy,and targeted therapy for advanced PHSC is still unclear.Therefore,it is essential for clinicians to have a comprehensive understanding of PHSC and to find the treatment methods for patients with different stages.ObjectiveIn this study,patient information was collected from domestic and foreign databases.We hope to summarize the clinical and pathological characteristics and treatment methods about PHSC by this method,and appropriate statistical methods were used to identify clinical factors that predicted patient outcomes.Furthermore,our research can provide some inspiration for clinicians.MethodsThe clinical data of 35 cases of PHSC patients diagnosed by pathology between January 2013 and January 2020 in the First Affiliated Hospital of Zhengzhou University and 94 cases of PHSC patients diagnosed by pathology between January 2005 and December 2015 in the SEER database of the National Cancer Institute were analyzed retrospectively in this study.The clinicopathological characteristics of PHSC were summarized according to the clinical manifestations,examination results,and treatment methods collected from the First Affiliated Hospital of Zhengzhou University.Based on patients’ survival data from the First Affiliated Hospital of Zhengzhou University and the SEER database,the Kaplan-Meier method was used to draw the survival curve,and comparisons were made using the log-rank test.We examined the prognostic factors by univariate and multivariate analysis(Cox proportional hazards regression model).Results1.A total of 129 PHSC patients were included in this study,with a male to female ratio of 2.39:1 and a median age of 62.Among all patients diagnosed with liver cancer in the First Affiliated Hospital of Zhengzhou University for seven years,the 35 PHSC patients accounted for 0.70%.2.The proportion of abdominal pain and fever in PHSC patients in the First Affiliated Hospital of Zhengzhou University was relatively high,with 54.3%and 34.3%,respectively.74.3%of patients were complicated with cirrhosis,and 62.9%had hepatitis virus infection.The proportion of patients with elevated AFP and CA-199 was 11.4%and 40%,respectively.HCC was mostly diagnosed in imaging examination,immunohistochemistry showed that the positive rates of Vimentin and CK were 100%,two cases showed TP53 gene mutation.3.There were a variety of antitumor drugs for advanced PHSC patients in the First Affiliated Hospital of Zhengzhou University,including chemotherapy drugs,immunotherapy drugs,and targeted drugs,only one patient with stage Ⅳ treated with paclitaxel liposome combined with toripalimab and apatinib achieved partial response in cycle 3,while the other patients with stage Ⅲ-Ⅳ not treated with the immune-combined regimen all experienced progressive disease after cycle 2-3.4.The median overall survival of the 129 patients was only three months,the 6-month survival rate was 26.9%,and the 1-year survival rate was 13.5%.Univariate analysis showed that T stage,M stage,AJCC stage,surgery or not,and treatment method were prognostic factors.Multivariate analysis showed that the treatment method was an independent prognostic factor for PHSC.Compared with non-surgery treatment,surgery significantly improved the prognosis in patients with stage Ⅰ-Ⅱ(median overall survival:13.0 months vs 2.0 months,P=0.006)and stage Ⅲ(median overall survival:4.0 months vs 2.0 months,P=0.035),but there was no statistically significant difference in overall survival with stage Ⅳ patients(median overall survival:4.0 months vs 2.0 months,P=0.204).The median overall survival of the group receiving subsequent treatment was longer than the group receiving surgery alone,but the difference was not statistically significant(P=0.224).Conclusions1.PHSC is rare clinically,mainly in older men with cirrhosis or hepatitis virus infection,and its clinical symptoms are mainly abdominal pain and fever.There are no specific imaging features and tumor markers,a confirmed diagnosis still requires pathological examination.2.PHSC progresses rapidly with a poor prognosis and a very low 1-year survival rate.The treatment method is an independent prognostic factor for PHSC.Surgery is an effective means to prolong patients’ survival time with early PHSC,but patients with Ⅳ stage don’t benefit from surgery.Advanced patients are not sensitive to most chemotherapy drugs and targeted drugs,immunotherapy may become a new direction for the treatment of advanced PHSC.