Prognostic value of programmed cell death ligand 1 (PD-L1) for hepatocellular carcinoma: a meta-analysis

Abstract The prognostic role of programmed death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been widely studied but the results are controversial. In this comprehensive meta-analysis, we elucidated the clinical value of PD-L1 in HCC. Relevant studies were systematically searched in the Cochrane Library, EMBASE, and PubMed until June 27, 2019. Eligible studies were validated for the prognostic effect of PD-L1 on the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) in HCC using a hazard ratio (HR) and its 95% confidence interval (95% CI). Twenty-three studies with 3529 patients were involved in this meta-analysis. The pooled results revealed that high membrane-bound PD-L1 (mPD-L1) expression was associated with poor OS (HR: 1.42; 95% CI: 1.12–1.80; P = 0.004) and had no significant correlation with RFS (HR: 1.14; 95% CI: 0.85–1.54; P = 0.39), and DFS (HR: 1.36; 95% CI: 0.81–2.28; P = 0.25). The results also indicated that high soluble PD-L1 (sPD-L1) levels were associated with worse OS (HR: 2.93; 95% CI: 2.20–3.91; P < 0.00001). In addition, high mPD-L1 expression was associated with high alpha-fetoprotein levels (AFP; OR = 1.46; 95% CI: 1.16–1.84; P = 0.001), hepatitis (OR = 0.72; 95% CI: 0.54–0.98; P = 0.03), poor tumor differentiation (OR = 0.68; 95% CI: 0.55–0.84; P = 0.03), and tumor-infiltrating lymphocytes (OR = 3.39; 95% CI: 1.06–10.91; P = 0.04). The mPD-L1 expression had no significant correlation with age, number of tumors, gender, tumor size, liver cirrhosis, vascular invasion, tumor encapsulation, or TNM stage. The study revealed that high mPD-L1 expression in the tumor tissue and high sPD-L1 levels were associated with shorter OS in HCC. Moreover, overexpression of mPD-L1 was significantly associated with poor tumor differentiation, hepatitis, AFP elevation, and tumor-infiltrating lymphocytes.

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Prognostic Value of Tumor Infiltrating Lymphocytes in Nasopharyngeal Carcinoma Patients: Meta-Analysis

Technology in Cancer Research & Treatment ◽

10.1177/15330338211034265 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110342

Author(s):

Birhanu Aberha Berele ◽

Yuxiang Cai ◽

Guifang Yang

Keyword(s):

Nasopharyngeal Carcinoma ◽

Prognostic Value ◽

Meta Analysis ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Cd4 Cells ◽

Free Survival ◽

Registration Number ◽

Infiltrating Lymphocytes ◽

Disease Free

Objective: To evaluate the prognostic value of tumor infiltrating lymphocytes (TILs) in nasopharyngeal carcinoma (NPC) patients. Method: Meta-analysis was performed on eligible studies that was identified by systematic searching of Google scholar, MEDLINE, CNKI, Scopus, PubMed, PMC, Embase and Web of Science databases. The study protocol was registered in International Platform of Registered Systematic Review and Meta-Analysis Protocols-INPLASY (registration number: INPLASY202160014). Databases were searched from inception to January 20, 2020 to identify eligible studies. Those studies that evaluated survival in the form of hazard ratio (HR) in TILs of NPC patients was analyzed. All statistical analysis was performed by using STATA version 16.0 software. Result: Fourteen studies with a total of 3025 patients was analyzed. The pooled result showed that high TILs was significantly associated with favorable overall survival (OS) (HR = 0.55; 95%CI = 0.39-0.77; P = 0.001) and disease free survival (DFS) (HR = 0.60; 95%CI = 0.44-0.81; P = 0.04). Interestingly, high intratumoral TILs had relatively better OS (HR = 0.45; 95%CI = 0.35-0.58; P = 0.006) than stromal TILs (HR = 0.59; 95%CI = 0.36-0.97; P = 0.03). Moreover, an increased level of CD4+ cells infiltration was correlated with favorable OS (HR = 0.4; 95%CI = 0.18-0.85; P = 0.01). CD3+, CD8+ and FoxP3+ lymphocyte’s better prognosis was not statistically significant for OS ( P = 0.09; P = 0.07; P = 0.52) and for DFS ( P = 0.13; P = 0.29) respectively. However, subgroup analysis of intratumoral CD3+ (HR = 0.48; 95%CI = 0.33-0.70; P = 0.05) and intratumoral CD8+ (HR = 0.32; 95%CI = 0.16-0.62; P = 0.001) was significantly associated with improved OS, but not significant in stromal CD3+ (HR = 0.66; 95%CI = 0.20-2.20; P = 0.62). Conclusion: TILs were variably correlated with better prognosis depending on their microanatomic location and subset of TILs in NPC patients. CD4+, intratumoral CD3+ and intratumoral CD8+ lymphocytes could predict favorable patient outcome which suggest that their role in mediating antitumor immune response could potentially be exploited in the treatment of NPC patients. Future large study on the prognostic value of microanatomic location of TILs is needed for confirmation.

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Prognostic Influence of Spontaneous Tumor Rupture in Patients with Hepatocellular Carcinoma After Hepatectomy: A Meta-Analysis of Observational Studies

10.21203/rs.3.rs-665806/v1 ◽

2021 ◽

Author(s):

Jiaxuan Xu ◽

Lihu Gu ◽

Binbin Xu ◽

Yuexiu Si ◽

Yujing He ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Risk Factor ◽

Hepatic Resection ◽

Meta Analysis ◽

Disease Free Survival ◽

Cochrane Library ◽

Tumor Rupture ◽

Free Survival ◽

Spontaneous Tumor ◽

Ruptured Hepatocellular Carcinoma

Abstract Background: This study aims to comprehensively analyze the influence of spontaneous tumor rupture on the prognosis of hepatocellular carcinoma patients following hepatic resection.Methods: We systematically searched four online electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, for eligible studies published from inception to March 2021. The main endpoints were overall survival (OS) and disease-free survival (DFS).Results: This meta-analysis included 21 observational articles with 57241 cases. The results revealed that spontaneous tumor rupture was associated with worse OS (hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.33-2.05) and DFS (HR, 1.42; 95% CI, 1.12-1.80) in resectable hepatocellular carcinoma patients. This phenomenon was observed in most subgroups, which were classified by recorded survival time, age, country, alpha-fetoprotein (AFP) concentration, liver cirrhosis, and microvascular invasion. However, in subgroups of macrovascular invasion positive, spontaneous tumor rupture was not a risk factor for OS (HR, 1.55; 95% CI, 0.99-2.42) and DFS (HR, 1.23; 95% CI, 0.91-1.65) in hepatocellular carcinoma patients after hepatectomy. For macrovascular invasion negative, compared with non-ruptured hepatocellular carcinoma patients, ruptured hepatocellular carcinoma patients exhibited worse prognosis for OS (HR, 1.55; 95% CI, 0.99-2.42) and DFS (HR, 1.23; 95% CI, 0.91-1.65) following hepatectomy.Conclusions: Spontaneous tumor rupture was a prognostic risk factor for hepatocellular carcinoma patients after hepatic resection. However, in macrovascular invasion patients, spontaneous tumor rupture was not a prognostic risk factor.

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Intratumoral immune cells expressing PD-1/PD-L1 and their prognostic implications in cancer: a meta-analysis

The International Journal of Biological Markers ◽

10.1177/1724600818770941 ◽

2018 ◽

Vol 33 (4) ◽

pp. 467-474 ◽

Cited By ~ 5

Author(s):

Younghoon Kim ◽

Xianyu Wen ◽

Nam Yun Cho ◽

Gyeong Hoon Kang

Keyword(s):

Overall Survival ◽

Immune Cells ◽

Meta Analysis ◽

Disease Free Survival ◽

Progression Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Free Survival ◽

Tissue Sections ◽

Infiltrating Lymphocytes ◽

Disease Free

Background: The prognostic value of immune cells expressing programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) in cancer are controversial, and the potential differential impact of using tissue microarrays and whole tissue sections to assess the positivity of immune cells has not been addressed. Methods: The current study included 30 eligible studies with 7251 patients that evaluated the relationship between tumor-infiltrating lymphocytes expressing PD-1/PD-L1 and overall survival and disease-free survival, or progression-free survival. Subgroup analysis was based on the tissue type of cancer and the type of tissue sampling (tissue microarray or whole tissue section). Results: In the meta-analysis, PD-1-positive and PD-L1-positive tumor-infiltrating lymphocytes had a positive effect on disease-free survival or progression-free survival (hazard ratio [HR] 0.732; 95% confidence interval [CI] 0.565, 0.947; and HR 0.727; 95% CI 0.584, 0.905, respectively). PD-L1-positive tumor-infiltrating lymphocytes had a positive impact on overall survival in studies using tissue microarray (HR 0.586; 95% CI 0.476, 0.721), but had a poor impact when only whole tissue sections were considered (HR 1.558; 95% CI 1.232, 1.969). Lung cancer was associated with good overall survival and disease-free survival (HR 0.639; 95% CI 0.491, 0.831; and HR 0.693; 95% CI 0.538, 0.891, respectively) for PD-1-positive tumor-infiltrating lymphocytes, and colorectal cancer showed favorable disease-free survival (HR 0.471; 95% CI 0.308, 0.722) for PD-L1-positive tumor-infiltrating lymphocytes. Conclusion: Immune cells expressing PD-1 and PD-L1 within tumors are associated with the prognosis. However, the correlation may vary among different tumor types and by the type of tissue sampling used for the assessment.

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Prognostic Influence of Spontaneous Tumor Rupture in Patients With Hepatocellular Carcinoma After Hepatectomy: A Meta-Analysis of Observational Studies

Frontiers in Surgery ◽

10.3389/fsurg.2021.769233 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jiaxuan Xu ◽

Jiaze Hong ◽

Yiran Wang ◽

Lingling Zhou ◽

Binbin Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Risk Factor ◽

Hepatic Resection ◽

Meta Analysis ◽

Disease Free Survival ◽

Cochrane Library ◽

Tumor Rupture ◽

Free Survival ◽

Spontaneous Tumor ◽

Ruptured Hepatocellular Carcinoma

Objective: This study aims to comprehensively analyze the influence of spontaneous tumor rupture on the prognosis of hepatocellular carcinoma patients following hepatic resection.Methods: We systematically searched four online electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, for eligible studies published from inception to March 2021. The main endpoints were overall survival (OS) and disease-free survival (DFS).Results: This meta-analysis included 21 observational articles with 57,241 cases. The results revealed that spontaneous tumor rupture was associated with worse OS (hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.33–2.05) and DFS (HR, 1.42; 95% CI, 1.12–1.80) in resectable hepatocellular carcinoma patients. This phenomenon was observed in most subgroups, which were classified by recorded survival time, age, country, alpha-fetoprotein (AFP) concentration, liver cirrhosis, and microvascular invasion. However, in subgroups of macrovascular invasion positive, spontaneous tumor rupture was not a risk factor for OS (HR, 1.55; 95% CI, 0.99–2.42) and DFS (HR, 1.23; 95% CI, 0.91–1.65) in hepatocellular carcinoma patients after hepatectomy. For macrovascular invasion negative, compared with non-ruptured hepatocellular carcinoma patients, ruptured hepatocellular carcinoma patients exhibited worse prognosis for OS (HR, 1.55; 95% CI, 0.99–2.42) and DFS (HR, 1.23; 95% CI, 0.91–1.65) following hepatectomy.Conclusions: Spontaneous tumor rupture was a prognostic risk factor for hepatocellular carcinoma patients after hepatic resection. However, in macrovascular invasion patients, spontaneous tumor rupture was not a prognostic risk factor.

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Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Cellular Physiology and Biochemistry ◽

10.1159/000487164 ◽

2018 ◽

Vol 45 (2) ◽

pp. 720-732 ◽

Cited By ~ 26

Author(s):

Xiao Zheng ◽

Xing Song ◽

Yingjie Shao ◽

Bin Xu ◽

Wenwei Hu ◽

...

Keyword(s):

Fixed Effects ◽

Meta Analysis ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Cochrane Library ◽

Prognostic Role ◽

Cancer Specific Survival ◽

Esophagus Cancer ◽

Infiltrating Lymphocytes

Background/Aims: Several studies have verified the correlation between tumor-infiltrating lymphocytes (TILs) and survival of patients with esophagus cancer (EC). However, the prognostic role of TILs is still controversial. Therefore, we performed this meta-analysis. Methods: We searched PubMed, Embase and the Cochrane Library (last update by August 30, 2017) to identify studies assessing the effect of TILs on survival of patients with EC. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and cancer specific survival (CSS) were estimated using fixed-effects models or random-effects models, which depends on the heterogeneity. Results: Data from 22 observational studies including 2909 patients were summarized. Pooled analysis indicated that generalized TILs were favorable prognostic markers for OS in patients with EC (pooled HR = 0.48; 95% CI = 0.38-0.61; P < 0.001). For TIL subsets, CD8+ TILs were associated with improved OS (pooled HR = 0.68; 95% CI = 0.58–0.84; P < 0.001) and DFS (pooled HR = 0.90; 95% CI = 0.85-0.95; P < 0.001); FoxP3+ TILs were associated with patients’ DFS (pooled HR = 0.88; 95% CI = 0.81-0.96; P = 0.003). High CD57+ TILs indicated a better OS in patients with EC (pooled HR = 0.50; 95% CI = 0.35-0.72; P < 0.001). In addition, the pooled results showed that other TIL subsets including CD3+, CD4+ and CD45RO+ TILs were not associated with patients’ survival (P > 0.05). Conclusions: For patients with EC, some TIL subsets could serve as prognostic biomarkers. The application of TILs in the immunotherapy of EC needs to be verified through a large amount of clinical research.

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The Prognostic Value of Intratumoral and Peritumoral Tumor-Infiltrating FoxP3+Treg Cells in of Pancreatic Cancers: A Meta-Analysis

10.21203/rs.3.rs-651950/v1 ◽

2021 ◽

Author(s):

Lingyu Hu ◽

Mingyuan Zhu ◽

Yiyu Shen ◽

Zhengxiang Zhong ◽

Bin Wu

Keyword(s):

Pancreatic Cancer ◽

Prognostic Value ◽

Meta Analysis ◽

Disease Free Survival ◽

Progression Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Treg Cells ◽

Cochrane Library ◽

Free Survival ◽

The Impact

Abstract Background: Tumor-infiltrating lymphocytes (TILs) are major participants in the tumor microenvironment. The prognostic value of TILs in patients with pancreatic cancer is still controversial. Methods: The aim of our meta-analysis was to determine the impact of FoxP3+Treg cells on the survival of pancreatic cancer patients.We searched for related studies in PubMed, EMBASE, Ovid and Cochrane Library from the time the databases were established to Mar 30, 2017. We identified studies reporting the prognostic value of FoxP3+Treg cells in patients with pancreatic cancer. Overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS)/relapse-free survival (RFS) were investigated by pooling the data. The pooled hazard ratios (HRs) with 95% confidence intervals (95% CI) were used to evaluate the association between FoxP3+Treg cells and survival outcomes of pancreatic cancer patients.A total of 972 pancreatic cancer patients from 8 studies were included in our meta-analysis. Results: High levels of infiltration with FoxP3+Treg cells were significantly associated with poor OS (HR=2.13; 95% CI: 1.64–2.77; P<0.05) and poor DFS/PFS/RFS (HR=1.70; 95% CI: 1.04 ~ 2.78; P< 0.05). Similar results were also observed in peritumoral tissue; high levels of FoxP3+Treg cells were associated with poor OS (HR =2.1795% CI, CI: 1.50–3.13).Conclusion: This meta-analysis indicated that high levels of intratumoral or peritumoral FoxP3+Treg cell infiltration could be recognized as a negative factor in the prognosis of pancreatic cancer.

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Safety of Simultaneous Hepatectomy and Splenectomy in the Treatment of Hepatocellular Carcinoma Complicated with Hypersplenism: A Meta-analysis

Gastroenterology Research and Practice ◽

10.1155/2019/9065845 ◽

2019 ◽

Vol 2019 ◽

pp. 1-17

Author(s):

Xuefeng Liu ◽

Zhiqiang Chen ◽

Meng Yu ◽

Wei Zhou ◽

Xuting Zhi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Meta Analysis ◽

Disease Free Survival ◽

Operation Time ◽

Cochrane Library ◽

Perioperative Mortality ◽

Free Survival ◽

Newcastle Ottawa Scale ◽

Disease Free ◽

Ottawa Scale

Background. We conducted this meta-analysis to compare the efficacy and safety of simultaneous hepatectomy and splenectomy (HS) with hepatectomy alone (HA) in patients with hepatocellular carcinoma (HCC) and hypersplenism. Materials and Methods. A systematic search was conducted in PubMed, Embase, Cochrane Library, and Wanfang Data through March 1, 2018, with no limits. Two investigators independently screened all retrieved studies. The investigators of the original publications were contacted if required information was absent. All the included studies were managed by EndNote X7. Quality assessment of the included studies was performed using a modified Newcastle-Ottawa Scale judgment. Extracted data for each endpoint were analyzed by using STATA 12.0 software. Results. Thirteen studies, including a total of 1468 patients, comparing the effects of HS with HA were pooled in this meta-analysis. Outcomes including postoperative complications, perioperative mortality, intraoperative blood transfusion, and albumin (ALB) content at postoperation day (POD) 7 did not differ significantly between the two groups. Simultaneous approaches significantly promoted 1-, 3-, and 5-year disease-free survival (DFS) rates and overall survival (OS) rates, prolonged operation time, aggravated intraoperative blood loss, increased white blood cell (WBC) and platelet (PLT) counts at POD 7, and lowered total bilirubin (T-Bil) contents at POD 1 and 7. Conclusion. Compared to HA, HS is safer and more effective in ameliorating liver function and improving survival of HCC patients complicated with hypersplenism. This trial is registered with CRD42018093779.

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Survival benefits from adjuvant transcatheter arterial chemoembolization in patients undergoing liver resection for hepatocellular carcinoma: a systematic review and meta-analysis

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284820977693 ◽

2020 ◽

Vol 13 ◽

pp. 175628482097769

Author(s):

Lei Liang ◽

Chao Li ◽

Yong-Kang Diao ◽

Hang-Dong Jia ◽

Hao Xing ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transcatheter Arterial Chemoembolization ◽

Meta Analysis ◽

Disease Free Survival ◽

Pooled Analysis ◽

Cochrane Library ◽

Free Survival ◽

Subgroup Analyses ◽

Disease Free ◽

Arterial Chemoembolization

Background: Although adjuvant transcatheter arterial chemoembolization (TACE) has been used to prevent recurrence after surgery in patients with hepatocellular carcinoma (HCC), the survival benefits from adjuvant TACE remain controversial. We sought to systematically evaluate the data on the effectiveness of adjuvant TACE for HCC, as well as identify patient populations that might benefit from adjuvant TACE. Methods: The PubMed, Embase, Medline and Cochrane library were systematically searched for studies published before July 2019 that compared adjuvant TACE versus surgery alone for HCC. The study endpoints were overall survival (OS) and disease-free survival (DFS). Patients with large HCC (⩾5 cm), multinodular HCC, microvascular invasion (MVI), or portal vein tumor thrombosis (PVTT) were analyzed in subgroup analyses. Results: Twenty-four studies with 6977 patients were included in the analytic cohort. The pooled analysis demonstrated that adjuvant TACE was associated with a better OS and DFS [hazard ratio (HR): 0.67 and 0.67, both p < 0.01]. In subgroup analyses, pooled results revealed that adjuvant TACE was associated with an improved OS and DFS in patients with multinodular HCC (HR: 0.79 and 0.31, both p < 0.01), MVI (HR: 0.62 and 0.67, both p < 0.01), or PVTT (HR: 0.49 and 0.58, both p < 0.01), but not among patients with large HCC (⩾5 cm). Conclusion: Postoperative adjuvant TACE may be effective to improve OS and DFS in patients with multinodular HCC, or HCC with MVI or PVTT. Future randomized controlled trials are needed to better define the benefit of adjuvant TACE in subset patients with HCC.

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Prognostic Value of Lactate Dehydrogenase in Patients with Hepatocellular Carcinoma: A Meta-Analysis

BioMed Research International ◽

10.1155/2018/1723184 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Weihao Kong ◽

Xiaomin Zuo ◽

Hao Liang ◽

Jingxiong Hu ◽

Huabing Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Sensitivity Analysis ◽

Lactate Dehydrogenase ◽

Publication Bias ◽

Subgroup Analysis ◽

Prognostic Value ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Free Survival

Background. Previous studies have shown the prognostic value of lactate dehydrogenase (LDH) in hepatocellular carcinoma (HCC), but the results are not persuasive. Therefore, the purpose of our study was to quantitatively explore the prognostic value of LDH in hepatocellular carcinoma.Methods. We searched the Web of Science, Embase, PubMed, and the Cochrane Library for literature published before October 2018 on the prognostic value of LDH in patients with hepatocellular carcinoma. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized to assess the prognostic value of LDH in overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) of HCC. Subgroup analysis, sensitivity analysis, and metaregression were used to explore the source of heterogeneity. Funnel plots with Begg’s test and Egger’s test were used to detect potential publication biases. Furthermore, combined odds ratios (ORs) were utilized to assess the correlation between LDH and clinicopathological features.Results. A total of 10 nonrandomized controlled studies were included in this meta-analysis. The combined effects of LDH on HCC patients’ OS, RFS/DFS, and PFS were HR = 2.07, 95% CI: 1.63-2.62, P < 0.001; HR = 1.62, 95% CI: 1.37-1.90, P < 0.001; and HR = 1.96, 95% CI: 1.14-3.36, P = 0.014, respectively. Subgroup analysis and sensitivity analysis showed that the outcome was stable, and the results of the metaregression also identified statistical models as an important source of heterogeneity. Potential publication bias was detected in the OS studies, so the trim-and-fill method was used to explore publication bias, and the results showed stability. Furthermore, the combined OR suggests that LDH was significantly correlated with gender, Child-Pugh grade, alpha-fetoprotein, vascular invasion, and tumor size.Conclusions. Preoperative LDH elevation is significantly associated with poor prognosis in patients with HCC, which may be a promising factor in assessing the prognosis of patients with HCC.

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Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers

Journal of Clinical Oncology ◽

10.1200/jco.18.01010 ◽

2019 ◽

Vol 37 (7) ◽

pp. 559-569 ◽

Cited By ~ 122

Author(s):

Sherene Loi ◽

Damien Drubay ◽

Sylvia Adams ◽

Giancarlo Pruneri ◽

Prudence A. Francis ◽

...

Keyword(s):

Triple Negative ◽

Early Stage ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Cox Proportional Hazards ◽

Prognostic Information ◽

Free Survival ◽

Node Negative ◽

Infiltrating Lymphocytes ◽

Disease Free

Purpose The aim of the current study was to conduct a pooled analysis of studies that have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in early-stage triple negative breast cancer (TNBC). Methods Participating studies had evaluated the percentage infiltration of stromally located TILs (sTILs) that were quantified in the same manner in patient diagnostic samples of early-stage TNBC treated with anthracycline-based chemotherapy with or without taxanes. Cox proportional hazards regression models stratified by trial were used for invasive disease-free survival (iDFS; primary end point), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors. Results We collected individual data from 2,148 patients from nine studies. Average age was 50 years (range, 22 to 85 years), and 33% of patients were node negative. The average value of sTILs was 23% (standard deviation, 20%), and 77% of patients had 1% or more sTILs. sTILs were significantly lower with older age ( P = .001), larger tumor size ( P = .01), more nodal involvement ( P = .02), and lower histologic grade ( P = .001). A total of 736 iDFS and 548 D-DFS events and 533 deaths were observed. In the multivariable model, sTILs added significant independent prognostic information for all end points (likelihood ratio χ2, 48.9 iDFS; P < .001; χ2, 55.8 D-DFS; P < .001; χ2, 48.5 OS; P < .001). Each 10% increment in sTILs corresponded to an iDFS hazard ratio of 0.87 (95% CI, 0.83 to 0.91) for iDFS, 0.83 (95% CI, 0.79 to 0.88) for D-DFS, and 0.84 (95% CI, 0.79 to 0.89) for OS. In node-negative patients with sTILs ≥ 30%, 3-year iDFS was 92% (95% CI, 89% to 98%), D-DFS was 97% (95% CI, 95% to 99%), and OS was 99% (95% CI, 97% to 100%). Conclusion This pooled data analysis confirms the strong prognostic role of sTILs in early-stage TNBC and excellent survival of patients with high sTILs after adjuvant chemotherapy and supports the integration of sTILs in a clinicopathologic prognostic model for patients with TNBC. This model can be found at www.tilsinbreastcancer.org .

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