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1.
Anticancer Res ; 40(12): 6971-6978, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33288591

ABSTRACT

BACKGROUND/AIM: We retrospectively investigated the significance of pre-treatment interferon-gamma release (IGR) as a biomarker for predicting the efficacy of immune checkpoint inhibitor treatment (ICI-tx). PATIENTS AND METHODS: This study included non-small-cell lung cancer patients who received ICI-tx between January 1, 2016 and April 30, 2019. IGR was measured using the positive control of an enzyme-linked immunosorbent assay. We defined the pre-treatment cut-off level of IGR as 10 IU/ml. RESULTS: Fifty-four patients were divided into two groups; those with an IGR ≤10 IU/ml (lower group: LG) (n=15) and those with >10 IU/ml (higher group: HG) (n=39). The time to treatment failure (TTF) in the HG was significantly longer than that in the LG. In multivariate analyses, C-reactive protein and IGR levels were significant risk factors for TTF. CONCLUSION: Pre-treatment IGR level of >10 IU/ml is recommended to identify those patients who will respond favourably to ICI-tx.


Subject(s)
Carcinoma, Non-Small-Cell Lung/blood , Interferon-gamma/blood , Lung Neoplasms/blood , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/therapeutic use , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Immune Checkpoint Inhibitors/therapeutic use , Interferon-gamma Release Tests , Kaplan-Meier Estimate , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Treatment Failure , Treatment Outcome
2.
Anticancer Res ; 40(5): 2787-2793, 2020 May.
Article in English | MEDLINE | ID: mdl-32366425

ABSTRACT

BACKGROUND/AIM: We aimed to study the association between the quantitative interferon-gamma (IFN-γ) levels and clinical outcomes in non-small-cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: Sample collection for IFN-γ release assay (IGRA) was performed within 14 days before treatment (T1), on day 22±7 (T3), and on day 43±7 (T4). The stored specimens over 10 IU/ml in IGRA were re-examined using the dilution method (with saline as the dilution medium). The patients were classified into Lower and Higher groups by 7.06 IU/ml as a cut-off of IFN-γ levels at T1. RESULTS: Median progression-free survival in the Higher group was significantly longer than that in the Lower group. IFN-γ levels in the non-progression disease group were significantly higher than those in the progression disease group. IFN-γ levels at T1 in patients with immune-related adverse events were significantly lower compared to those at T3. CONCLUSION: IFN-γ could be a biomarker for NSCLC patients receiving ICIs.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Immunotherapy/methods , Interferon-gamma/metabolism , Lung Neoplasms/genetics , Disease Progression , Female , Humans , Male , Progression-Free Survival
3.
Anticancer Res ; 39(11): 6231-6240, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31704852

ABSTRACT

BACKGROUND/AIM: The present study aimed to prospectively examine the usefulness of interferon-gamma (IFN-γ) release (IGR) as a biomarker in non-small-cell lung cancer patients receiving immune checkpoint inhibitor treatment (ICI-Tx). PATIENTS AND METHODS: IGR was measured using enzyme-linked immunosorbent assay at four time points: within 14 days before ICI-Tx (T1), and 8±3 (T2), 22±7 (T3), and 43±7 (T4) days after ICI-Tx. RESULTS: Twenty-nine patients were divided into three groups based on IFN-γ levels in the IGR-positive control: Group-1 (n=8) with <10 IU/ml at T1, Group-2 (n=12) with a decrease in IFN-γ levels to <10 IU/ml at T3 and/or T4, and Group-3 (n=9) without changes in IFN-γ levels. Early progression and ICI-induced interstitial pneumonitis were frequently observed in Group-1 and Group-2, respectively. Group-3 exhibited more treatment cycles than the other groups. All three groups showed clear differences in clinical outcomes. CONCLUSION: IFN-γ levels could be a biomarker for ICI-Tx.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Interferon-gamma/metabolism , Lung Neoplasms/metabolism , T-Lymphocytes/metabolism , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/metabolism , Biomarkers, Tumor/blood , Carcinoma, Non-Small-Cell Lung/drug therapy , Disease Progression , Female , Humans , Immunotherapy/adverse effects , Immunotherapy/methods , Interferon-gamma/blood , Latent Tuberculosis/diagnosis , Latent Tuberculosis/etiology , Latent Tuberculosis/metabolism , Lung Diseases, Interstitial/etiology , Lung Neoplasms/therapy , Male , Middle Aged , Nivolumab/therapeutic use , Prospective Studies , T-Lymphocytes/immunology , Time Factors
4.
Respir Med Case Rep ; 28: 100862, 2019.
Article in English | MEDLINE | ID: mdl-31194139

ABSTRACT

The present report describes the case of a 64-year-old woman with advanced lung adenocarcinoma expressing mutant epidermal growth factor receptor (EGFR). The patient developed follicular lymphoma during treatment with the EGFR-tyrosine kinase inhibitor afatinib. Standard immunochemotherapy for follicular lymphoma was introduced in addition to continuing treatment with afatinib for lung cancer. Immunochemotherapy was effective and improved the patient's performance status while afatinib controlled the progression of lung cancer. Our case study suggests that it is safe to introduce standard immunochemotherapy for patients who develop malignant lymphoma while continuing treatment with tyrosine kinase inhibitors for lung adenocarcinoma expressing mutant EGFR.

5.
Rinsho Byori ; 56(4): 290-6, 2008 Apr.
Article in Japanese | MEDLINE | ID: mdl-18516963

ABSTRACT

More than 1 asbestos body (AB) per ml of bronchoalveolar lavage fluid (BALF) under light microscopy was defined as AB positive (ABP) and suggests an occupational asbestos exposure. We microscopically evaluated the AB number per one ml of BALF, which we defined as the AB concentration (ABC), using bronchoalveolar lavage (BAL) cytocentrifuge slides obtained from 35 patients having pulmonary nodular lesions (20 carcinoma and 15 nonneoplastic disease) and examined the correlation between ABC and clinicopathological data including findings on Helical computed tomography scan (HCTS) and occupational history of asbestos exposure (OHAE). BAL was performed by the standard technique without removing mucous with a gauze filter. AB was microscopically defined as a structure consisting of a core of transparent asbestos surrounded by an iron-protein coat. Twenty of 35 patients were ABP (ABP rate; 57%) and ABC ranged from 0 to 207.98/ml (mean ABC; 11.33/ml). Mean ABC was significantly higher in patients with OHAE (15.04/ml) compared to that in patients without OHAE (3.23/ml). Twenty-two of 35 patients (63%) lacked abnormality on HCTS and among these, 12 patients (55%) were ABP. In 20 pulmonary carcinoma patients, the ABP rate was 85% and ABC ranged from 0 to 31.1/ml (Mean ABC; 2.99/ml). The ABP rate of pulmonary carcinoma patients was 40% (8 patients) and among these, 5 patients (63%) did not show any abnormality on HCTS. In conclusion, our method was simple and useful and should be applied to patients with pulmonary nodular lesions and OHAE, even if there are no abnormalities on HCTS.


Subject(s)
Asbestos/adverse effects , Asbestos/analysis , Asbestosis/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Carcinoma/metabolism , Lung Neoplasms/metabolism , Microscopy , Occupational Exposure/adverse effects , Adult , Aged , Aged, 80 and over , Female , Histocytochemistry/methods , Humans , Male , Middle Aged
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