Will liquid biopsies improve outcomes for patients with small-cell lung cancer?

Blackhall, Fiona; Frese, Kristopher K.; Simpson, Kathryn; Kilgour, Elaine; Brady, Ged; Dive, Caroline

doi:10.1016/s1470-2045(18)30455-8

Cited by 54 publications

(40 citation statements)

References 100 publications

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“…The median survival of limited-stage SCLC has been reported to be 15-20 months, indicating that this cancer extremely malignant (22). For limited-stage SCLC that is not suitable for surgery, the accepted standard treatment is CCRT (23). However, there is much debate about whether radiotherapy should be BID or OD (24).…”

Section: Discussionmentioning

confidence: 99%

A Meta-Analysis of the Efficacy and Toxicity of Twice-Daily vs. Once-Daily Concurrent Chemoradiotherapy for Limited-Stage Small Cell Lung Cancer Based on Randomized Controlled Trials

Xiong

Zhang

et al. 2020

Front. Oncol.

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Background: Currently, the accepted standard management of limited-stage small cell lung cancer (SCLC) is concurrent chemoradiotherapy (CCRT), but the frequency of radiotherapy is controversial. Therefore, this meta-analysis, which compared the efficacy and toxicity between twice-daily (BID) and once-daily (OD) CCRT, was performed to help clinicians make better decisions. Methods: Relevant randomized controlled trials (RCTs) were collected by searching the PubMed, Ovid MEDLINE, Embase, ScienceDirect, Web of Science, the Cochrane Library, Scopus and Google Scholar databases to assess antitumor effects (overall survival, OS; progression-free survival, PFS; overall response rate, ORR) and toxicity (adverse effects, AEs). Results: We screened 1499 articles and included 5 RCTs including 1421 patients. We found that BID CCRT improved OS (hazard ratio, HR = 0.88, 95% confidence interval, CI 0.78-0.99, p = 0.03), the 1-year OS rate (OSR-1y, risk ratio, RR = 1.07, 95%CI 1.01-1.13, p = 0.03), and OSR-4y (RR = 1.22, 95%CI 1.03-1.43, p = 0.02), with better trends in OSR-2y, OSR-3y, and OSR-5y, compared to OD CCRT. In addition, BID CCRT had a higher complete response (CR, RR = 1.31, 95%CI 1.01-1.70, p = 0.04) than OD CCRT. PFS (HR = 0.92, 95%CI 0.79-1.07, p = 0.29), annual PFS rate, ORR (RR = 0.99, 95%CI 0.93-1.05, p = 0.72), and AEs for all grades (RR = 1.00, 95%CI 0.98-1.01, p = 0.57), and grades 3-5 (RR = 1.02, 95%CI 0.95-1.09, p = 0.60) were similar between the two arms. Conclusions: BID CCRT appears to be better than OD CCRT for limited-stage SCLC, with better antitumor effects (OS, OSR, and CR) and similar AEs. However, the high levels of AEs in both arms should be taken as a sign of caution. More large sample and high-quality RCTs need to be conducted to confirm our conclusions.

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Section: Discussionmentioning

confidence: 99%

A Meta-Analysis of the Efficacy and Toxicity of Twice-Daily vs. Once-Daily Concurrent Chemoradiotherapy for Limited-Stage Small Cell Lung Cancer Based on Randomized Controlled Trials

Xiong

Zhang

et al. 2020

Front. Oncol.

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“…26,521,552 SCLC is a highly aggressive neuroendocrine tumor with characteristics of neuroendocrine organ-like nest-like structure, a rapid growth rate, and a natural propensity for early metastatic spread, not typically observed in patients with no history of smoking. [553][554][555] The first description of this trans-differentiation was a case report showing that a 45-yearold patient diagnosed with EGFR-mutant lung adenocarcinoma had obtained a partial response to erlotinib treatment, but 18 months later relapsed with metastatic synaptophysin (a typical neuroendocrine marker)-positive SCLC in multiple organs, with no trace of adenocarcinoma at autopsy. 556 The contributions made by neuroendocrine trans-differentiation to the resistance to TKIbased therapy in EGFR-mutant NSCLC have been excellently presented in a number of recent reviews.…”

Section: Transition Between Non-csc and Csc States Definition And Chamentioning

confidence: 99%

Emerging role of tumor cell plasticity in modifying therapeutic response

Qin

Jiang

Lü

et al. 2020

Sig Transduct Target Ther

153

122

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Resistance to cancer therapy is a major barrier to cancer management. Conventional views have proposed that acquisition of resistance may result from genetic mutations. However, accumulating evidence implicates a key role of non-mutational resistance mechanisms underlying drug tolerance, the latter of which is the focus that will be discussed here. Such non-mutational processes are largely driven by tumor cell plasticity, which renders tumor cells insusceptible to the drug-targeted pathway, thereby facilitating the tumor cell survival and growth. The concept of tumor cell plasticity highlights the significance of re-activation of developmental programs that are closely correlated with epithelial–mesenchymal transition, acquisition properties of cancer stem cells, and trans-differentiation potential during drug exposure. From observations in various cancers, this concept provides an opportunity for investigating the nature of anticancer drug resistance. Over the years, our understanding of the emerging role of phenotype switching in modifying therapeutic response has considerably increased. This expanded knowledge of tumor cell plasticity contributes to developing novel therapeutic strategies or combination therapy regimens using available anticancer drugs, which are likely to improve patient outcomes in clinical practice.

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“…Additionally, we cannot analyze the RNA transcriptome and proteome of the tumor via ctDNA [136]. Furthermore, despite the marker-based enrichment method of CTCs, they are phenotypically heterogeneous, which limits its effectiveness, and markers could be downregulated during different stages of cancer, such as during EMT [137]. As for cf-miRs, they are prone to contamination from several sources, including cell-derived miRNA from puncture site and lysed red blood cells, platelets, and leucocytes from circulation.…”

Section: Advantages Of Utilizing Exosomes Over Ctcs Cfdna/ctdna Andmentioning

confidence: 99%

Exosomal Non Coding RNA in LIQUID Biopsies as a Promising Biomarker for Colorectal Cancer

Baassiri

Nassar

Mukherji

et al. 2020

IJMS

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Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, especially in those that are diagnosed in late stages of the disease. The current screening blood-based markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), have low sensitivity and specificity. Meanwhile, other modalities are either expensive or invasive. Therefore, recent research has shifted towards a minimally invasive test, namely, liquid biopsy. Exosomes are favorable molecules sought in blood samples, since they are abundant, stable in circulation, and harbor genetic information and other biomolecules that could serve as biomarkers or even therapeutic targets. Furthermore, exosomal noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, have demonstrated the diagnostic potential to detect CRC at an early stage with a higher sensitivity and specificity than CEA and CA19-9 alone. Moreover, they have prognostic potential that is TNM stage specific and could serve as predictive biomarkers for the most common chemotherapeutic drug and combination regimen in CRC, which are 5-FU and FOLFOX, respectively. Therefore, in this review, we focus on the role of these exosomal noncoding RNAs as diagnostic, prognostic, and predictive biomarkers. In addition, we discuss the advantages and challenges of exosomes as a liquid biopsy target.

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Will liquid biopsies improve outcomes for patients with small-cell lung cancer?

Cited by 54 publications

References 100 publications

A Meta-Analysis of the Efficacy and Toxicity of Twice-Daily vs. Once-Daily Concurrent Chemoradiotherapy for Limited-Stage Small Cell Lung Cancer Based on Randomized Controlled Trials

A Meta-Analysis of the Efficacy and Toxicity of Twice-Daily vs. Once-Daily Concurrent Chemoradiotherapy for Limited-Stage Small Cell Lung Cancer Based on Randomized Controlled Trials

Emerging role of tumor cell plasticity in modifying therapeutic response

Exosomal Non Coding RNA in LIQUID Biopsies as a Promising Biomarker for Colorectal Cancer

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