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1.
Ther Adv Med Oncol ; 14: 17588359221138386, 2022.
Article in English | MEDLINE | ID: mdl-36506107

ABSTRACT

Background: A significant proportion of patients with non-small-cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICIs). Since metabolic reprogramming with increased glycolysis is a hallmark of cancer and is involved in immune evasion, we used 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) to evaluate the baseline glycolytic parameters of patients with advanced NSCLC submitted to ICIs, and assessed their predictive value. Methods: 18F-FDG PET/CT results in the 3 months before ICIs treatment were included. Maximum standardized uptake values, whole metabolic tumor volume (wMTV), and whole-body total lesion glycolysis (wTLG) were evaluated. Cutoff values for high or low glycolytic categories were determined using receiver-operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were evaluated. Patients with a complete response and a matching group with resistance to ICIs underwent immunohistochemistry analysis. An unsupervised k-means clustering model integrating programmed cell death ligand 1 (PD-L1) expression, glycolytic parameters, and ICIs therapy was performed. Results: In all, 98 patients were included. Lower baseline 18F-FDG PET/CT parameters were associated with responses to ICIs. Patients with low wMTV or wTLG had improved PFS and OS. High wTLG, strong tumor expression of glucose transporter-1, and lack of responses were significantly associated. Patients with low glycolytic parameters benefited from ICIs, regardless of chemotherapy. Conversely, those with high parameters benefited from the addition of chemotherapy. Patients with higher wTLG and lower PD-L1 were associated with progression and worse survival to ICIs monotherapy. Conclusions: Glycolytic metabolic profiles established through baseline 18F-FDG PET/CT are useful biomarkers for evaluating ICI therapy in advanced NSCLC.

2.
Clin Lung Cancer ; 22(5): e708-e711, 2021 09.
Article in English | MEDLINE | ID: mdl-33658161

ABSTRACT

Immunotherapy based on immune checkpoint inhibitors (ICIs) either alone or in combination with platinum-based chemotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer. However, only a subset of patients derives clinical benefits. Although programmed death-ligand 1 (PD-L1) and tumor mutational burden (TMB) are known to be prognostic and demonstrated utility in selecting patients for immunotherapy response, they are imperfect biomarkers. Recent evidence demonstrates that AT-rich interaction domain 1A (ARID1A) deficiency is associated with high antitumor immunity, mismatch repair and TMB, and thus may potentially contribute as a predictive biomarker for ICIs. We herein describe a 60-year-old woman, former smoker, who was diagnosed with lung adenocarcinoma metastatic to the left adrenal gland, with a PD-L1 expression of 60%. Next-generation sequencing test revealed an ARID1A mutation (F2141fs*59, variant allele frequency = 22.5%), TMB of 92 mut/Mb and stable microsatellite status. Given the high PD-L1 expression, elevated TMB, and ARID1A mutation, the patient started on first-line treatment with pembrolizumab monotherapy, and, 5 months after initiating treatment, presented an expressive reduction of lung lesion and a complete response of the adrenal gland. This case illustrates a dramatic response to ICI monotherapy in a lung cancer patient with ARID1A mutation. Predictive biomarkers for immune checkpoint blockade are of the utmost importance to select the patients who truly benefit from immunotherapy. The combination of biomarkers may be the most effective strategy to improve outcomes with ICIs, and ARID1A status should definitely be taken into account when present.


Subject(s)
Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/pathology , Antibodies, Monoclonal, Humanized/administration & dosage , DNA-Binding Proteins/genetics , Mutation/genetics , Transcription Factors/genetics , Female , Humans , Immunotherapy , Middle Aged , Treatment Outcome
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