Progression-free Survival In Cancer Patients Research Articles

A novel whole blood purifier for efficient capture and separation of circulating tumor cells

Circulating tumor cells (CTCs) as important biomarkers for noninvasive clinical diagnosis and prognostic evaluation are significant in predicting the overall survival and progression-free survival of cancer patients. However, the current typical CTCs separation and enrichment techniques were limited to a single collection of small-volume blood samples, which was inadequate to comprehensively profile the distribution of CTCs in the systemic blood. In addition, those techniques cannot reduce metastasis of CTCs unless adjuvant chemotherapy. Herein, inspired by hemodialysis, we designed a whole blood purifier (WBP) composed of a functionalized special spiral-like glass tube modified by anti-epithelial cell adhesion molecule (anti-EpCAM). The WBP allowed real-time capture, enrichment and removal of CTCs from systemic blood circulation, and the purified blood was immediately returned to the body. Furthermore, the WBP did not cause any organic damages in vivo. This approach achieves the high accuracy of liquid biopsy technology and is expected to become an effective clinical adjuvant therapy for tumor metastasis.

Systemic immune-inflammation index predicts prognosis of cancer immunotherapy: systemic review and meta-analysis.

Objective: This meta-analysis was designed to explore the association between the systemic immune-inflammation index (SII) and the therapeutic effect of immune checkpoint inhibitors. Materials & methods: The authors retrieved relevant studies published before May 25, 2022. Hazard ratio (HR) with 95% CI was used to evaluate the relationship between SII and overall survival (OS) and progression-free survival (PFS). Results: 14articles comprising 2721 patients were included in this study. The pooled results proved that high SII levels were closely related to poor prognosis in cancer patients receiving immune checkpoint inhibitors (OS HR = 2.40; 95% CI: 2.04-2.82; PFS HR = 1.57; 95% CI: 1.33-1.86) and that an SII value of 750 was appropriate as a cut-off value (OS HR = 2.20; 95% CI: 1.83-2.63; PFS HR = 1.54; 95% CI: 1.33-1.80). Conclusion: High SII levels (>750) may be an indicator of worse OS and PFS in cancer patients treated with immune checkpoint inhibitors.

Soluble PD-L1 as a Prognostic Factor for Immunotherapy Treatment in Solid Tumors: Systematic Review and Meta-Analysis.

Blocking the Programmed Cell Death Protein 1 (PD-1)/programmed death ligand-1 (PD-L1) axis has demonstrated great efficacy in cancer immunotherapy treatment and remains the central modality of immune targeting. To support the rational and tailored use of these drugs, it is important to identify reliable biomarkers related to survival. The role of the soluble form of the PD-L1 (sPD-L1) as a prognostic biomarker related to survival in solid cancer patients treated with immunotherapy has not yet been consistently evaluated. A systematic literature search of original articles in PubMed, MEDLINE and Scopus was conducted. Studies reporting hazard ratios (HRs) with a 95% confidence interval (CI) or Kaplan-Meier curves or individual patient data for overall survival (OS) or progression-free survival (PFS) associated with baseline levels of sPD-L1 in cancer patients undergoing immunotherapy treatment were considered eligible. Twelve studies involving 1076 patients and different tumor types treated with immunotherapy were included in the analysis. High blood levels of sPD-L1 correlated with poorer OS and PFS in cancer patients treated with immunotherapy (HR = 1.49, 95%CI: 1.15, 1.93, p < 0.01, I2 = 77% for OS; HR = 1.59, 95%CI: 1.20, 2.12, p < 0.01, I2 = 82% for PFS). A subgroup analysis highlighted that high levels of sPD-L1 were associated with worse survival in patients affected by NSCLC (HR = 1.81 95%CI: 1.09-3.00, p = 0.02, I2 = 83% for OS; HR = 2.18, 95%CI: 1.27-3.76, p < 0.01, I2 = 88% for PFS). An HR > 1 indicated that patients with low levels of sPD-L1 have the highest rates of OS/PFS. In this meta-analysis, we clarified the role of sPD-L1 in different solid cancers treated exclusively with Immune checkpoint inhibitors (ICIs). sPD-L1 could represent a non-invasive biomarker that is easily dosable in the blood of patients. The pooled data from the selected studies showed that a high circulating concentration of sPD-L1 in cancer patients correlates with worse survival, suggesting that it may be a helpful prognostic biomarker for the selection of cancer patients before immunotherapy, thus improving the efficacy of ICIs and avoiding unnecessary treatment.

Lack of Efficacy of Immune Checkpoint Inhibitors in Cancer Patients Older Than 75?

This research was designed to compare the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients among different age groups. Electronic databases were searched to identify relevant trials. Randomized-controlled trials (RCTs) with ICIs and RCTs that conducted subgroup analysis of overall survival (OS) and/or progression-free survival (PFS) based on age were included. Summary hazard ratio (HR) and 95% confidence interval (CI) were available. Totally, 35,777 individuals from 59 RCTs were recruited. ICIs can ameliorate OS and PFS of cancer patients in groups of below 65 year and 65-75 years. Conversely, patients in group of 75 years or above failed to acquire benefit from ICIs for both OS (HR=0.99, 95% CI: 0.91-1.09, P =0.8767) and PFS (HR=0.96, 95% CI: 0.82-1.11, P =0.5694). Subgroup analysis was performed based on class of ICIs, type of ICIs, type of cancer, line of treatment, blind method, and type of nonsmall-cell lung cancer. In all subgroups, OS and PFS were not significantly improved in patients 75 years or above. Cancer patients older than 75 years failed to acquire remarkable benefit from ICIs for both OS and PFS.

The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: a systematic review and meta-analysis.

Background:Immune-related adverse events (irAEs) are common during immune checkpoint inhibitor (ICI) treatment and reported to be associated with good survival. This study evaluated the association between onset timing of irAEs and survival of cancer patients treated with ICIs.Methods:Databases including PubMed, Embase, and the Cochrane library were systematically searched to retrieve clinical studies assessing the relationship between irAEs and survival in cancer patients with ICIs. The overall response rate for treatment response and hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were calculated using RevMan 5.3. Subgroup analysis in terms of cancer type, ICIs type, region, specific irAEs, accordingly.Results:A total of 34 studies were included. The HRs for OS and PFS in cancer patients with versus without irAEs were 0.57 [95% confidence interval (CI): 0.44, 0.74; p < 0.0001], and 0.50 (95% CI: 0.37, 0.67; p < 0.00001), respectively. The odds ratio for overall response in cancer patients with irAEs was 4.72 (95% CI: 3.48, 6.40; p < 0.00001) compared with those without irAEs. Subgroup analyses suggested that the prognostic role of irAEs was associated with cancer types and region, but not irAEs types. The landmark analysis of OS revealed that there is a non-proportional (early) effect of irAEs on OS in ICI-treated cancer patients (landmark >12 weeks, HROS = 1.08; 95% CI: 0.89, 1.30; p = 0.46).Conclusion:Our findings suggest that the occurrence of irAEs could be a prognostic factor for cancer patients who were treated with ICIs.

The association of speckle-type POZ protein with lymph node metastasis and prognosis in cancer patients: A meta-analysis.

Speckle-type POZ protein (SPOP) has recently been reported as a prognostic tumor biomarker. However, the predictive value of SPOP remains controversial in human cancers. The current meta-analysis was performed to obtain a comprehensive evaluation of the relationship between SPOP expression and prognosis of cancer patients. Embase, Pubmed, Web of Science, and Chinese Biomedical Literature database were systematically searched up to January 2, 2019. The pooled hazard ratios (HRs) and/or pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantitatively assess the relationship of SPOP expression with prognosis and lymph node metastasis (LNM). A total of 9 studies with 928 patients were included in this meta-analysis. The results showed that low SPOP expression was significantly related to poor overall survival (high/low: HR = 0.55; 95% CI: 0.38-0.79, P = .001), especially for digestive system cancers (high/low: HR = 0.46; 95% CI: 0.27-0.78, P = .003). However, SPOP expression did not affect progression-free survival in cancer patients (high/low: HR = 2.07; 95% CI: 0.16-26.70, P = .578). Additionally, the association between SPOP overexpression and LNM was positive in patients with clear cell renal cell carcinoma (ccRCC) (OR = 5.26; 95% CI: 1.66-16.68, P = .005) but negative in cancer patients without ccRCC (OR = 0.36; 95% CI: 0.21-0.62, P < .001). Decreased SPOP expression could predict poor prognosis of cancer patients, suggesting that SPOP protein may be a useful prognostic biomarker in cancer patients.

Antibiotic use and the efficacy of immune checkpoint inhibitors in cancer patients: a pooled analysis of 2740 cancer patients

ABSTRACTThe gut microbiota plays a critical role in the anti-tumor immune response. There is increasing data showing that antibiotics (ATBs) change the composition of the gut microbiota and affect the efficacy of immune checkpoint inhibitors (ICIs). However, this is the first meta-analysis to evaluate the association between ATB use and ICI efficacy in cancer patients to provide a better understanding of the strength of this association. We performed a literature search for relevant studies that evaluated the relationship between ATB use and ICI efficacy using the PubMed, Embase, and conference databases. The primary outcomes consisted of overall survival (OS) and progression-free survival (PFS) measured by hazard ratios (HR) and corresponding 95% confidence intervals (CI). Subgroup and sensitivity analyses were also performed. A total of 19 eligible studies comprising 2,740 cancer patients treated with ICIs were included in the analysis. Our results indicated that ATB use was negatively associated with OS in cancer patients (HR = 2.37; 95% CI = 2.05–2.75; P < .001), without heterogeneity (I2 = 0.0%; P = .851). Moreover, ATB use significantly reduced PFS in patients treated with ICIs (HR = 1.84; 95% CI = 1.49–2.26; P < .001; I2 = 56.2%). Similar results were obtained in the subgroup analyses stratified by the time of ATB use and cancer type. Sensitivity analyses confirmed the stability of our results. Therefore, the findings of our meta-analysis indicated that ATB use is negatively associated with OS and PFS in cancer patients treated with ICI immunotherapy.

ADAM17 overexpression is associated with poorer clinical outcomes in cancer patients: a systematic review and meta-analysis

// XuFeng Peng 1, * , Bo Hao 3, * , Nailong Cao 1 , Jihong Wang 1 , Xiangguo Lv 2 and XinRu Zhang 1 1 Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China 2 Department of Urology and Andrology, Shanghai Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200001, China 3 Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China * These authors have contributed equally to this work Correspondence to: XinRu Zhang, email: 15800558925@163.com Xiangguo Lv, email: chnlvsc@163.com Keywords: ADAM17; cancer; prognosis; lymph node metastasis; distant metastasis Received: July 15, 2017 Accepted: December 26, 2017 Published: January 02, 2018 ABSTRACT ADAM17 (a disintegrin and metalloproteinase 17) is overexpressed in many types of cancer, and its high expression in cancer patients is associated with increased risk of metastasis and a poorer prognosis. However, the clinical value of ADAM17 as a tumor biomarker remains largely unknown. In this meta-analysis, we investigated the relationships between ADAM17 levels, cancer metastasis, and patient prognosis. Twelve eligible studies involving a total of 1816 patients were identified in searches of the PubMed, Embase, Cochrane, and Chinese National Knowledge Infrastructure databases. Analysis of these studies revealed that ADAM17 overexpression is positively associated with lymph node metastasis in a fixed effect model and distant metastasis in a random effect model. Moreover, high ADAM17 expression was predictive of shorter overall and progression-free survivalof cancer patients in fixed effect models. These results suggest that ADAM17 maybe a useful biomarker for predicting metastasis and prognosis in cancer patients and may also aid in risk stratification and selection of individualized treatments.

Mathematical Modeling of Therapy-induced Cancer Drug Resistance: Connecting Cancer Mechanisms to Population Survival Rates

Drug resistance significantly limits the long-term effectiveness of targeted therapeutics for cancer patients. Recent experimental studies have demonstrated that cancer cell heterogeneity and microenvironment adaptations to targeted therapy play important roles in promoting the rapid acquisition of drug resistance and in increasing cancer metastasis. The systematic development of effective therapeutics to overcome drug resistance mechanisms poses a major challenge. In this study, we used a modeling approach to connect cellular mechanisms underlying cancer drug resistance to population-level patient survival. To predict progression-free survival in cancer patients with metastatic melanoma, we developed a set of stochastic differential equations to describe the dynamics of heterogeneous cell populations while taking into account micro-environment adaptations. Clinical data on survival and circulating tumor cell DNA (ctDNA) concentrations were used to confirm the effectiveness of our model. Moreover, our model predicted distinct patterns of dose-dependent synergy when evaluating a combination of BRAF and MEK inhibitors versus a combination of BRAF and PI3K inhibitors. These predictions were consistent with the findings in previously reported studies. The impact of the drug metabolism rate on patient survival was also discussed. The proposed model might facilitate the quantitative evaluation and optimization of combination therapeutics and cancer clinical trial design.

Effect of angiogenesis inhibitor bevacizumab on survival in patients with cancer: a meta-analysis of the published literature.

Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor which has been used in conjunction with other anti-cancer agents in the treatment of patients with many cancers. It remains controversial whether bevacizumab can prolong survival in cancer patients. This meta-analysis was therefore performed to evaluate effect of bevacizumab on survival in cancer patients. PubMed, EMBASE, and Web of Science databases were searched for English-language studies of randomized controlled trials comparing bevacizumab with control therapy published through February 8, 2012. Progression-free survival, overall survival, and one-year survival rate were analyzed using random- or fixed-effects model. Thirty one assessable randomized controlled trials were identified. A significant improvement in progression-free survival in cancer patients was attributable to bevacizumab compared with control therapy (hazard ratio, 0.72; 95% confidence interval, 0.68 to 0.76; p<0.001). Overall survival was also significantly longer in patients were treated with bevacizumab (hazard ratio, 0.87; 95% confidence interval, 0.83 to 0.91; p<0.001). The significant benefit in one-year survival rate was further seen in cancer patients receiving bevacizumab (odds ratio, 1.30; 95% confidence interval, 1.20 to 1.41; p<0.001). Current evidences showed that bevacizumab prolong progression-free survival and overall survival, and increase one-year survival rate in cancer patients as compared with control therapy.