Prognostic and Predictive Biomarkers in Non-Small Cell Lung Cancer Patients on Immunotherapy—The Role of Liquid Biopsy in Unraveling the Puzzle

Augustus, Elien; Zwaenepoel, Karen; Siozopoulou, Vasiliki; Raskin, Jo; Jordaens, Stephanie; Baggerman, Geert; Sorber, Laure; Roeyen, Geert; Peeters, Marc; Pauwels, Patrick

doi:10.3390/cancers13071675

Cited by 21 publications

(16 citation statements)

References 107 publications

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“…Rebiopsies of lung tumors are difficult to perform in the clinical setting, and immunoscoring (e.g., PD-L1 analysis) is mostly done only once at diagnosis; therefore, the results are not applicable for longitudinal monitoring of responses (26). For lung cancer diagnostics, "liquid biopsies" are performed when tissue biopsy procurement is too hazardous or when therapy resistance develops [25][26][27]. Such blood-based analysis aims to identify genomic features with the rationale that tumor DNA is leaking from the cancer tissue into the bloodstream [28].…”

Section: Discussionmentioning

confidence: 99%

Plasma Proteomic Analysis in Non-Small Cell Lung Cancer Patients Treated with PD-1/PD-L1 Blockade

Eltahir

Isaksson

Mattsson

et al. 2021

Cancers

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Checkpoint inhibitors have been approved for the treatment of non-small cell lung cancer (NSCLC). However, only a minority of patients demonstrate a durable clinical response. PD-L1 scoring is currently the only biomarker measure routinely used to select patients for immunotherapy, but its predictive accuracy is modest. The aim of our study was to evaluate a proteomic assay for the analysis of patient plasma in the context of immunotherapy. Pretreatment plasma samples from 43 NSCLC patients who received anti-PD-(L)1 therapy were analyzed using a proximity extension assay (PEA) to quantify 92 different immune oncology-related proteins. The plasma protein levels were associated with clinical and histopathological parameters, as well as therapy response and survival. Unsupervised hierarchical cluster analysis revealed two patient groups with distinct protein profiles associated with high and low immune protein levels, designated as “hot” and “cold”. Further supervised cluster analysis based on T-cell activation markers showed that higher levels of T-cell activation markers were associated with longer progression-free survival (PFS) (p < 0.01). The analysis of single proteins revealed that high plasma levels of CXCL9 and CXCL10 and low ADA levels were associated with better response and prolonged PFS (p < 0.05). Moreover, in an explorative response prediction model, the combination of protein markers (CXCL9, CXCL10, IL-15, CASP8, and ADA) resulted in higher accuracy in predicting response than tumor PD-L1 expression or each protein assayed individually. Our findings demonstrate a proof of concept for the use of multiplex plasma protein levels as a tool for anti-PD-(L)1 response prediction in NSCLC. Additionally, we identified protein signatures that could predict the response to anti-PD-(L)1 therapy.

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Section: Discussionmentioning

confidence: 99%

Plasma Proteomic Analysis in Non-Small Cell Lung Cancer Patients Treated with PD-1/PD-L1 Blockade

Eltahir

Isaksson

Mattsson

et al. 2021

Cancers

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“…e commonly used biomarkers for liquid biopsy include circulating tumor DNA (ctDNA), CTCs, exosomes, and circulating tumor RNA (ctRNA). Currently, only ctDNA and CTC have been approved for clinical use by the FDA [33,34]. Zhang et al tested CTC in patients with bladder cancer planned for surgery and found that 44 cases (86.3%) were positive [35].…”

Section: Discussionmentioning

confidence: 99%

Application of Circulating Tumor Cells and Circulating Free DNA from Peripheral Blood in the Prognosis of Advanced Gastric Cancer

Zhu

Luo

et al. 2022

Journal of Oncology

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Objective. To explore the application value of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood in the prognosis of advanced gastric cancer (AGC). Here, we measured CTCs and cfDNA quantity for predicting the outcome of patients. Patients and Methods. Forty-five patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and surgical treatment were enrolled in this study. All patients received neoadjuvant chemotherapy with paclitaxel + S-1 + oxaliplatin (PSOX) regimen, and CTCs and cfDNA of the peripheral blood were detected before and after neoadjuvant therapy. Relationships between the number/type of CTC or cfDNA and the efficacy of neoadjuvant chemotherapy were analyzed. Results. Among 45 patients, 43 (95.6%) were positive, and the positive rate of mesenchymal CTC was increased with the increase in the T stage. The proportion of mesenchymal CTC was positively correlated with the N stage ( P < 0.05 ), and the larger N stage will have the higher proportion of mesenchymal CTC. Patients with a small number of mesenchymal CTC before neoadjuvant chemotherapy were more likely to achieve partial response (PR) with neoadjuvant therapy. Patients with positive CA-199 were more likely to achieve PR with neoadjuvant therapy ( P < 0.05 ). Patients in the PR group were more likely to have decreased/unchanged cfDNA concentration after neoadjuvant therapy ( P = 0.119 ). After neoadjuvant therapy (before surgery), the cfDNA concentration was higher and the efficacy of neoadjuvant therapy (SD or PD) was lower ( P = 0.045 ). Conclusions. Peripheral blood CTC, especially interstitial CTC and cfDNA, has a certain value in predicting the efficacy and prognosis of neoadjuvant chemotherapy in advanced gastric cancer.

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“…Circulating tumor cells, circulating DNA, microRNA, extracellular vesicles and epigenetic signatures, among others, are commonly determined in blood, urine and saliva samples, while volatile compounds and gut microbiota are determined in breath and feces samples, respectively. [ 63 ]. However, blood samples are the ones most commonly utilized.…”

Section: Potential Future Refinementsmentioning

confidence: 99%

“…However, blood samples are the ones most commonly utilized. The determination of biomarkers in liquid biopsy is useful in early diagnosis of lung cancer [ 64 , 65 ], in monitoring patients and genetic alterations during therapy [ 63 , 66 ], in characterizing molecular tumor profile [ 66 , 67 ], in assessing prognosis [ 68 ] and in detecting minimal residual disease in early stage lung cancer after curative resection [ 69 ]. Regarding the latter, Wu et al determined the circulating tumor cell count before and after resection on the day of surgery, and on postoperative days 1 and 3 in 41 patients with lung cancer, 30 (80%) adenocarcinomas.…”

Section: Potential Future Refinementsmentioning

confidence: 99%

The Evolving Concept of Complete Resection in Lung Cancer Surgery

Rami–Porta

2021

Cancers

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Different definitions of complete resection were formulated to complement the residual tumor (R) descriptor proposed by the American Joint Committee on Cancer in 1977. The definitions went beyond resection margins to include the status of the visceral pleura, the most distant nodes and the nodal capsule and the performance of a complete mediastinal lymphadenectomy. In 2005, the International Association for the Study of Lung Cancer (IASLC) proposed definitions for complete, incomplete and uncertain resections for international implementation. Central to the IASLC definition of complete resection is an adequate nodal evaluation either by systematic nodal dissection or lobe-specific systematic nodal dissection, as well as the integrity of the highest mediastinal node, the nodal capsule and the resection margins. When there is evidence of cancer remaining after treatment, the resection is incomplete, and when all margins are free of tumor, but the conditions for complete resection are not fulfilled, the resection is defined as uncertain. The prognostic relevance of the definitions has been validated by four studies. The definitions can be improved in the future by considering the cells spread through air spaces, the residual tumor cells, DNA or RNA in the blood, and the determination of the adequate margins and lymphadenectomy in sublobar resections.

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Prognostic and Predictive Biomarkers in Non-Small Cell Lung Cancer Patients on Immunotherapy—The Role of Liquid Biopsy in Unraveling the Puzzle

Cited by 21 publications

References 107 publications

Plasma Proteomic Analysis in Non-Small Cell Lung Cancer Patients Treated with PD-1/PD-L1 Blockade

Plasma Proteomic Analysis in Non-Small Cell Lung Cancer Patients Treated with PD-1/PD-L1 Blockade

Application of Circulating Tumor Cells and Circulating Free DNA from Peripheral Blood in the Prognosis of Advanced Gastric Cancer

The Evolving Concept of Complete Resection in Lung Cancer Surgery

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