Independent expression of circulating and tissue levels of PD-L1: correlation of clusters with tumor metabolism and outcome in patients with non-small cell lung cancer

Grizzi, Fabio; Castello, Angelo; Qehajaj, Dorina; Toschi, Luca; Rossi, Sabrina; Pistillo, Daniela; Paleari, Valentina; Veronesi, Giulia; Novellis, Pierluigi; Monterisi, Simona; Mineri, Rossana; Rahal, Daoud; Lopci, Egesta

doi:10.1007/s00262-019-02387-9

Cited by 10 publications

(9 citation statements)

References 46 publications

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“…On the contrary, SUVmax did not show significant association with both PFS and OS. These results are in accordance with recent studies, suggesting a superior correlation of volumetric 18F-FDG PET/CT parameters, rather than SUVmax only [7,9,20,21]. However, despite the fact that in the Kaplan-Meier analysis, MTV and TLG showed a trend in predicting disease…”

Section: Discussionsupporting

confidence: 92%

“…Focusing on the relationship between quantitative biological features and cancer prognosis by non-invasive method and aiding clinicians in selecting the appropriate treatments, radiomics is considered a step toward the application of personalized medicine in routine practice. In this respect, NSCLC is a key example to show the advantages of a tailored approach [8,9].…”

Section: Introductionmentioning

confidence: 99%

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18F-FDG Pet Parameters and Radiomics Features Analysis in Advanced Nsclc Treated with Immunotherapy as Predictors of Therapy Response and Survival

Polverari

Ceci

Bertaglia

et al. 2020

Cancers

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Objectives: (1.1) to evaluate the association between baseline 18F-FDG PET/CT semi-quantitative parameters of the primary lesion with progression free survival (PFS), overall survival (OS) and response to immunotherapy, in advanced non-small cell lung carcinoma (NSCLC) patients eligible for immunotherapy; (1.2) to evaluate the application of radiomics analysis of the primary lesion to identify features predictive of response to immunotherapy; (1.3) to evaluate if tumor burden assessed by 18F-FDG PET/CT (N and M factors) is associated with PFS and OS. Materials and Methods: we retrospectively analyzed clinical records of advanced NCSLC patients (stage IIIb/c or stage IV) candidate to immunotherapy who performed 18F-FDG PET/CT before treatment to stage the disease. Fifty-seven (57) patients were included in the analysis (F:M 17:40; median age = 69 years old). Notably, 38/57 of patients had adenocarcinoma (AC), 10/57 squamous cell carcinoma (SCC) and 9/57 were not otherwise specified (NOS). Overall, 47.4% patients were stage IVA, 42.1% IVB and 8.8% IIIB. Immunotherapy was performed as front-line therapy in 42/57 patients and as second line therapy after chemotherapy platinum-based in 15/57. The median follow up after starting immunotherapy was 10 months (range: 1.5–68.6). Therapy response was assessed by RECIST 1.1 criteria (CT evaluation every 4 cycles of therapy) in 48/57 patients or when not feasible by clinical and laboratory data (fast disease progression or worsening of patient clinical condition in nine patients). Radiomics analysis was performed by applying regions of interest (ROIs) of the primary tumor delineated manually by two operators and semi-automatically applying a threshold at 40% of SUVmax. Results: (1.1) metabolic tumor volume (MTV) (p = 0.028) and total lesion glycolysis (TLG) (p = 0.035) were significantly associated with progressive vs. non-progressive disease status. Patients with higher values of MTV and TLG had higher probability of disease progression, compared to those patients presenting with lower values. SUVmax did not show correlation with PD status, PFS and OS. MTV (p = 0.027) and TLG (p = 0.022) also resulted in being significantly different among PR, SD and PD groups, while SUVmax was confirmed to not be associated with response to therapy (p = 0.427). (1.2) We observed the association of several radiomics features with PD status. Namely, patients with high tumor volume, TLG and heterogeneity expressed by “skewness” and “kurtosis” had a higher probability of failing immunotherapy. (1.3) M status at 18F-FDG PET/CT was significantly associated with PFS (p = 0.002) and OS (p = 0.049). No significant associations were observed for N status. Conclusions: 18F-FDG PET/CT performed before the start of immunotherapy might be an important prognostic tool able to predict the disease progression and response to immunotherapy in patients with advanced NSCLC, since MTV, TLG and radiomics features (volume and heterogeneity) are associated with disease progression.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

18F-FDG Pet Parameters and Radiomics Features Analysis in Advanced Nsclc Treated with Immunotherapy as Predictors of Therapy Response and Survival

Polverari

Ceci

Bertaglia

et al. 2020

Cancers

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“…CTCs are a noninvasive, surrogate sample accessible to longitudinal sampling and could provide a snapshot of PD-L1 status in patients. Detection of PD-L1 positive (PD-L1 + ) CTCs and their prognostic potential have been demonstrated in NSCLC [186][187][188][189][190][191][192][193], BC [194], urothelial carcinoma [195], gastric cancer [196], cholangiocarcinoma [17], and melanoma [197]. Dynamic changes in the expression of PD-L1 in response to radiotherapy have also been reported in a study in NSCLC [191].…”

Section: Pd-l1 Expression On Ctcsmentioning

confidence: 75%

Relevance of Circulating Tumor Cells as Predictive Markers for Cancer Incidence and Relapse

2022

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Shedding of cancer cells from the primary site or undetectable bone marrow region into the circulatory system, resulting in clinically overt metastasis or dissemination, is the hallmark of unfavorable invasive cancers. The shed cells remain in circulation until they extravasate to form a secondary metastatic lesion or undergo anoikis. The circulating tumor cells (CTCs) found as single cells or clusters carry a plethora of information, are acknowledged as potential biomarkers for predicting cancer prognosis and cancer progression, and are supposed to play key roles in determining tailored therapies for advanced diseases. With the advent of novel technologies that allow the precise isolation of CTCs, more and more clinical trials are focusing on the prognostic and predictive potential of CTCs. In this review, we summarize the role of CTCs as a predictive marker for cancer incidence, relapse, and response to therapy.

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“…As disease-related biomarkers continue to be discovered at widely varying concentrations within biofluid, the need for signal amplification techniques will become ever more important to meet the challenge of ultra-sensitive detection. Biomarkers such as programmed death-ligand 1 (PD-L1), a transmembrane ligand that suppresses the adaptive immune system through binding to its receptor PD-1, 150 have been implicated in non-small cell lung carcinoma 151 , 152 and breast cancer 153 at sub-ng mL-1 concentrations, below the reliable detection limits of a traditional colorimetric ELISA. Similarly, earlier detection of biomarkers such as cardiac troponin I, which are only detectable in blood during pathological conditions such as acute myocardial infarction, 154–156 are enabled by more sensitive techniques that have lower limits of detection, providing opportunities for earlier intervention and potentially improved clinical outcomes.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Challenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics

Lengfeld¹,

Zhang²,

Stoesz³

et al. 2021

BCTT

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Breast cancer is a highly prevalent malignancy that shows improved outcomes with earlier diagnosis. Current screening and monitoring methods have improved survival rates, but the limitations of these approaches have led to the investigation of biomarker evaluation to improve early diagnosis and treatment monitoring. The enzyme-linked immunosorbent assay (ELISA) is a specific and robust technique ideally suited for the quantification of protein biomarkers from blood or its constituents. The continued clinical relevancy of this assay format will require overcoming specific technical challenges, including the ultra-sensitive detection of trace biomarkers and the circumventing of potential assay interference due to the expanding use of monoclonal antibody (mAb) therapeutics. Approaches to increasing the sensitivity of ELISA have been numerous and include employing more sensitive substrates, combining ELISA with the polymerase chain reaction (PCR), and incorporating nanoparticles as shuttles for detection antibodies and enzymes. These modifications have resulted in substantial boosts in the ability to detect extremely low levels of protein biomarkers, with some systems reliably detecting antigen at sub-femtomolar concentrations. Extensive utilization of mAb therapies in oncology has presented an additional contemporary challenge for ELISA, particularly when both therapeutic and assay antibodies target the same protein antigen. Resolution of issues such as epitope overlap and steric hindrance requires a rational approach to the design of diagnostic antibodies that takes advantage of modern antibody generation pipelines, epitope binning techniques and computational methods to strategically target biomarker epitopes. This review discusses technical strategies in ELISA implemented to date and their feasibility to address current constraints on sensitivity and problems with interference in the clinical setting. The impact of these recent advancements will depend upon their transformation from research laboratory protocols into facile, reliable detection systems that can ideally be replicated in point-of-care devices to maximize utilization and transform both the diagnostic and therapeutic monitoring landscape.

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Independent expression of circulating and tissue levels of PD-L1: correlation of clusters with tumor metabolism and outcome in patients with non-small cell lung cancer

Cited by 10 publications

References 46 publications

18F-FDG Pet Parameters and Radiomics Features Analysis in Advanced Nsclc Treated with Immunotherapy as Predictors of Therapy Response and Survival

18F-FDG Pet Parameters and Radiomics Features Analysis in Advanced Nsclc Treated with Immunotherapy as Predictors of Therapy Response and Survival

Relevance of Circulating Tumor Cells as Predictive Markers for Cancer Incidence and Relapse

Challenges in Detection of Serum Oncoprotein: Relevance to Breast Cancer Diagnostics

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