Objective:Hyper-progression recurrence(HPR)after hepatectomy is a specific recurrence pattern associated with extremely poor prognosis in patients with hepatocellular carcinoma(HCC).This study was aimed at investigati...Objective:Hyper-progression recurrence(HPR)after hepatectomy is a specific recurrence pattern associated with extremely poor prognosis in patients with hepatocellular carcinoma(HCC).This study was aimed at investigating the probable risk factors and establishing comprehensive models for formulating clinical strategies.Methods:Overall,16,158 patients with HCC from 8 hospitals were screened,among whom 3,125 patients who underwent R0 resection were included,and divided into development(n=2,113)and validation(n=1,012)cohorts.A comprehensive study of HPR predictive models and biological features was conducted.Results:Among the 3,125 enrolled patients,506(16.19%)developed HPR.The influence of HPR on extremely poor prognosis was reflected by recurrence features,adverse effects on systemic and liver function,and limited therapeutic options.Nine variables closely associated with HPR were identified,and incorporated into nomogram and conditional inference tree models,which successfully achieved pre-and post-operative HPR risk stratification and facilitated clinical decision-making.Multi-dimensional verification also confirmed the predictive accuracy of model combinations and their reliability in clinical applications.Furthermore,biological analyses revealed that HCCs with HPR exhibited hyperactive biological processes,inactive metabolism,and immune exhaustion features,together with high MYCN/HMGA2 co-expression,thereby enhancing understanding of the molecular events leading to HPR and providing valuable knowledge for HPR management.Conclusions:HPR after hepatectomy is associated with extremely poor prognosis and requires substantial attention.We constructed comprehensive predictive models and propose a clinical strategy for guiding HPR prevention and management.展开更多
Immune checkpoint inhibitors(ICIs)are gradually replacing chemotherapy as the cornerstone of the treatment of advanced malignant tumors because of their long-lasting and significant effect in different tumor types and...Immune checkpoint inhibitors(ICIs)are gradually replacing chemotherapy as the cornerstone of the treatment of advanced malignant tumors because of their long-lasting and significant effect in different tumor types and greatly prolonging the survival time of patients.However,not all patients can respond to ICIs,and even rapid tumor growth after treatment with ICI has been observed in a number of clinical studies.This rapid progression phenomenon is called hyper-progressive disease(HPD).The occurrence of HPD is not uncommon.Past statistics show that the incidence of HPD is 4%-29% in different tumor types,and the progression-free survival and overall survival of patients with HPD are significantly shorter than those of the non-HPD progressor group.With the deepening of the study of HPD,we have established a preliminary understanding of HPD,but the diagnostic criteria of HPD are still not unified,and the addition of biomarkers may break this dilemma.In addition,quite a few immune cells have been found to be involved in the occurrence and development of HPD in the tumor microenvironment,indicating that the molecular mechanism of HPD may be triggered by a variety of ongoing events at the same time.In this review,we summarize past findings,including case reports,clinical trials,and fundamental research;compare the diagnostic criteria,incidence,and clinical prognostic indicators of HPD in different studies;and explore the molecular mechanism and future research direction of HPD.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.NSFC 82273405,and 81972306)supported partly by the Guangxi Nature Sciences grants(Grant No.2018GXNSFAA138028)the Guangxi Medical University Training Program for Distinguished Young Scholars.
文摘Objective:Hyper-progression recurrence(HPR)after hepatectomy is a specific recurrence pattern associated with extremely poor prognosis in patients with hepatocellular carcinoma(HCC).This study was aimed at investigating the probable risk factors and establishing comprehensive models for formulating clinical strategies.Methods:Overall,16,158 patients with HCC from 8 hospitals were screened,among whom 3,125 patients who underwent R0 resection were included,and divided into development(n=2,113)and validation(n=1,012)cohorts.A comprehensive study of HPR predictive models and biological features was conducted.Results:Among the 3,125 enrolled patients,506(16.19%)developed HPR.The influence of HPR on extremely poor prognosis was reflected by recurrence features,adverse effects on systemic and liver function,and limited therapeutic options.Nine variables closely associated with HPR were identified,and incorporated into nomogram and conditional inference tree models,which successfully achieved pre-and post-operative HPR risk stratification and facilitated clinical decision-making.Multi-dimensional verification also confirmed the predictive accuracy of model combinations and their reliability in clinical applications.Furthermore,biological analyses revealed that HCCs with HPR exhibited hyperactive biological processes,inactive metabolism,and immune exhaustion features,together with high MYCN/HMGA2 co-expression,thereby enhancing understanding of the molecular events leading to HPR and providing valuable knowledge for HPR management.Conclusions:HPR after hepatectomy is associated with extremely poor prognosis and requires substantial attention.We constructed comprehensive predictive models and propose a clinical strategy for guiding HPR prevention and management.
文摘Immune checkpoint inhibitors(ICIs)are gradually replacing chemotherapy as the cornerstone of the treatment of advanced malignant tumors because of their long-lasting and significant effect in different tumor types and greatly prolonging the survival time of patients.However,not all patients can respond to ICIs,and even rapid tumor growth after treatment with ICI has been observed in a number of clinical studies.This rapid progression phenomenon is called hyper-progressive disease(HPD).The occurrence of HPD is not uncommon.Past statistics show that the incidence of HPD is 4%-29% in different tumor types,and the progression-free survival and overall survival of patients with HPD are significantly shorter than those of the non-HPD progressor group.With the deepening of the study of HPD,we have established a preliminary understanding of HPD,but the diagnostic criteria of HPD are still not unified,and the addition of biomarkers may break this dilemma.In addition,quite a few immune cells have been found to be involved in the occurrence and development of HPD in the tumor microenvironment,indicating that the molecular mechanism of HPD may be triggered by a variety of ongoing events at the same time.In this review,we summarize past findings,including case reports,clinical trials,and fundamental research;compare the diagnostic criteria,incidence,and clinical prognostic indicators of HPD in different studies;and explore the molecular mechanism and future research direction of HPD.
