Upregulated miRNA‑182‑5p expression in tumor tissue and peripheral blood samples from patients with non‑small cell lung cancer is associated with downregulated Caspase 2 expression

Background: n-ELAV (neuronal-Embryonic Lethal, Abnormal Vision)-like genes belong to a family codifying for onconeural RNA-binding proteins. Anti-Hu-antibodies (anti-Hu-Ab) are typically associated with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN), and low titres of anti-Hu-Ab, were found in newly diagnosed Small Cell Lung Cancer (SCLC). The aim of this study is to develop a sensitive and quantitative molecular real-time PCR assay to detect SCLC cells in peripheral blood (PB) through nELAV-like transcripts quantification.Methods: Peripheral blood samples from 25 SCLC untreated patients and 12 healthy blood donors were investigated by realtime PCR. mRNA levels for HuB (ELAV2), HuC (ELAV3) and HuD (ELAV4) were measured in peripheral blood samples with an absolute quantification method using plasmid dilutions as calibration curves.Results: A statistically significant increase in mRNA expression level was detected for HuB and HuD in SCLC patients as compared with samples from healthy blood donors. After establishing cut off values based on the level of expression in control samples, 28% of the SCLC samples were positive for HuD expression. Overall 60% of the SCLC displayed increased level of HuD or HuB transcripts.Conclusion: Our preliminary results suggest that neuron-ELAV mRNA are detectable in peripheral blood of SCLC patients using real-time quantitative PCR.

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7P Peripheral blood-based biomarkers of prognosis and treatment response in patients with non-small cell lung cancer treated with PD-1 inhibitors

Annals of Oncology ◽

10.1016/j.annonc.2020.10.492 ◽

2020 ◽

Vol 31 ◽

pp. S1419

Author(s):

I. Tourkantonis ◽

D. Grapsa ◽

A. Charpidou ◽

I. Gkiozos ◽

H. Gogas ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Treatment Response ◽

Cell Lung Cancer ◽

Peripheral Blood ◽

Small Cell ◽

Small Cell Lung

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Durvalumab and tremelimumab with or without stereotactic body radiation therapy in relapsed small cell lung cancer: a randomized phase II study

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001302 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001302

Author(s):

Suchita Pakkala ◽

Kristin Higgins ◽

Zhengjia Chen ◽

Gabriel Sica ◽

Conor Steuer ◽

...

Keyword(s):

Lung Cancer ◽

T Cells ◽

Radiation Therapy ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Peripheral Blood ◽

Stereotactic Body Radiation Therapy ◽

Small Cell ◽

Small Cell Lung ◽

Stereotactic Body Radiation

BackgroundImmune checkpoint blockade (ICB) targeting programmed cell death protein 1 and cytotoxic T lymphocyte-associated protein 4 has achieved modest clinical activity as salvage therapy in relapsed small cell lung cancer (SCLC). We conducted this signal-finding study to assess the efficacy of ICB with or without radiation in relapsed SCLC.MethodsPatients with relapsed SCLC and ≤2 previous lines of therapy were randomized to (1) arm A: durvalumab (D) 1500 mg/tremelimumab (T) 75 mg (intravenously every 4 weeks without stereotactic body radiation therapy (SBRT)) or (2) arm B: immune-sensitizing SBRT to one selected tumor site (9 Gy × 3 fractions) followed by D/T. Treatment continued until progression or a maximum of 12 months. The co-primary endpoints of the study were overall response rate (ORR) and progression-free survival (PFS). We evaluated circulating lymphocyte repertoire in serial peripheral blood samples and tumor infiltrating lymphocytes (TILs) from on-treatment biopsies as pharmacodynamic markers.ResultsEighteen patients were randomized to arms A and B (n=9 each): median age 70 years; 41.2% women. The median PFS and ORR were 2.1 months and 0% in arm A and 3.3 months and 28.6% in arm B. The median overall survival (OS) was 2.8 months in arm A and 5.7 months in arm B (p=0.3772). Pooled efficacy of D/T±SBRT in 15 Response evaluation criteria in solid tumors (RECIST) evaluable patients across both arms showed the best ORR in terms of partial response in 13.3%, stable disease in 26.6% and progressive disease in 60.0%; the overall median PFS and OS were 2.76 and 3.9 months. The most common adverse events were grade 1 fatigue (66%) and grade 1 elevated amylase (56%) in arm A, and grade 1 fatigue (56%) and pain (44%) in arm B. There was a significant increase in activated CD8(+)ICOS+ T cells (p=0.048) and a reduction in naïve T cells (p=0.0454) in peripheral blood following treatment, along with a significant amount of activated CD8+ICOS+ T cells in TILs from responders.ConclusionsThe D/T combination with and without SBRT was safe but did not show sufficient efficacy signal in relapsed SCLC. Changes in peripheral blood lymphocyte and TILs were consistent with an immunologic response.Trial registration numberNCT02701400.

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