Dataset Information

Impact of pre-existing interstitial lung abnormal shadow on lung injury development and severity in patients of non-small cell lung cancer treated with osimertinib.

ABSTRACT:

Background

First-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sometimes causes lung injury, thereby affecting survival. Although pre-existing interstitial lung abnormal shadow (pre-ILS) increases the risk of lung injury by EGFR-TKIs, its impact on osimertinib, a third-generation EGFR-TKI, remains unknown.

Patients and methods

This retrospective cohort study consecutively enrolled patients of EGFR-mutated non-small cell lung cancer treated with osimertinib. Computed tomography images were obtained and evaluated independently by three pulmonologists in a blinded manner. Factors associated with lung injury were assessed using a logistic regression model. Survival curves were calculated by the Kaplan-Meier method and compared using a log-rank test.

Results

Of the 195 patients, 40 had pre-ILS, and 21 (8 with and 13 without pre-ILS) developed lung injury during the observation period. Multivariate analysis revealed that pre-ILS was independently associated with lung injury (odds ratio, 3.1; 95% confidence interval [CI], 1.1-8.2; p = 0.025). Severe (≥Grade 3) lung injury was observed in eight (4.1%) patients, of whom, two (5%) and six (3.9%) had and did not have pre-ILS (p = 0.67), respectively. Grade 5 lung injury was not observed, and survival curves were similar between the patients who developed lung injury and those who did not (median 11 vs. 12 months; hazard ratio, 1.2; 95% CI, 0.56-2.7; p = 0.60).

Conclusions

Pre-ILS increased the risk of lung injury in patients of non-small cell lung cancer treated with osimertinib, while the severity of lung injury was not clearly affected by the presence of pre-ILS.

SUBMITTER: Shibaki R

PROVIDER: S-EPMC9582680 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of pre-existing interstitial lung abnormal shadow on lung injury development and severity in patients of non-small cell lung cancer treated with osimertinib.

Shibaki Ryota R Ozawa Yuichi Y Noguchi Susumu S Murakami Yusuke Y Takase Eri E Azuma Yuichiro Y Maebeya Masaru M Sugimoto Takeya T Hayata Atsushi A Hayakawa Takahiro T Tamaki Shinya S Nakanishi Masanori M Teraoka Shunsuke S Akamatsu Hiroaki H

Cancer medicine 20220417 20

<h4>Background</h4>First-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sometimes causes lung injury, thereby affecting survival. Although pre-existing interstitial lung abnormal shadow (pre-ILS) increases the risk of lung injury by EGFR-TKIs, its impact on osimertinib, a third-generation EGFR-TKI, remains unknown.<h4>Patients and methods</h4>This retrospective cohort study consecutively enrolled patients of EGFR-mutated non-small cell lung cancer treated with o ...[more]

PMID: 35434933

Similar Datasets

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have demonstrated efficacy over previous cytotoxic chemotherapies in clinical trials among various tumors. Despite their favorable outcomes, they are associated with a unique set of toxicities termed as immune-related adverse events (irAEs). Among the toxicities, ICI-related pneumonitis has poor outcomes with little understanding of its risk factors. This retrospective study aimed to investigate whether pre-existing interstitial lung abnormality (ILA) is a potential risk factor for ICI-related pneumonitis.Materials and methodsPatients with non-small cell lung cancer, malignant melanoma, renal cell carcinoma, and gastric cancer, who was administered either nivolumab, pembrolizumab, or atezolizumab between September 2014 and January 2019 were retrospectively reviewed. Information on baseline characteristics, computed tomography findings before administration of ICIs, clinical outcomes, and irAEs were collected from their medical records. Pre-existing ILA was categorized based on previous studies.ResultsTwo-hundred-nine patients with a median age of 68 years were included and 23 (11.0%) developed ICI-related pneumonitis. While smoking history and ICI agents were associated with ICI-related pneumonitis (P = .005 and .044, respectively), the categories of ILA were not associated with ICI-related pneumonitis (P = .428). None of the features of lung abnormalities were also associated with ICI-related pneumonitis. Multivariate logistic analysis indicated that smoking history was the only significant predictor of ICI-related pneumonitis (P = .028).ConclusionThis retrospective study did not demonstrate statistically significant association between pre-existing ILA and ICI-related pneumonitis, nor an association between radiologic features of ILA and ICI-related pneumonitis. Smoking history was independently associated with ICI-related pneumonitis. Further research is warranted for further understanding of the risk factors of ICI-related pneumonitis.

Project description:BackgroundLung cancer patients with comorbid interstitial lung disease (LC-ILD) have an increased risk of developing severe or even fatal radiation pneumonitis after thoracic radiotherapy. However, the underlying mechanisms of its pathogenesis are still inconclusive. No approved biomarker or medicine is available to prevent pulmonary toxicities in LC-ILD patients. Appropriate management for them remains a challenge for clinicians due to treatment-related complications.MethodsTo elucidate the histopathological characteristics and molecular mechanisms responsible for this severe toxicity in vivo, C57BL/6J mice were used to develop different lung injury models, including radiation-induced lung injury (RILI), bleomycin-induced pulmonary fibrosis (BIPF), and severe radiation-related lung injury (sRRLI) murine model. Biopsy examination was performed on hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemistry-stained lung tissue sections. Changes in lung function were measured. RNA extracted from mouse lung tissues was sequenced on the Illumina Novaseq platform.ResultsA severe lung injury model after irradiation was built based on pre-existing ILD mice induced by BLM administration. Enhanced lung injury was observed in the sRRLI model, including higher mortality and pulmonary function loss within six months compared to the mono-treatment groups. Autopsy revealed that bilateral diffuse alveolar damage (DAD) with an overlap of exudative, proliferative, and fibrosing patterns was usually presented in the sRRLI model. The histological phenotypes manifested exudative predominated DAD phase in the early phase and proliferating DAD pattern in the late phase. Bioinformatic analysis showed signaling pathways relevant to immune cell migration, epithelial cell development, and extracellular structure organization were commonly activated in different models. Furthermore, the involvement of epithelial cells and the infiltration of macrophages and CD4 + lymphocytes were validated during extensive lung remodeling in the sRRLI group.ConclusionsDelayed effects of significantly declined lung function and high mortality were observed in the sRRLI model. DAD with progressive inflammation and fibrosis in bilateral lungs contributed to severe or even fatal complications after partial thoracic irradiation. The hyperactivation of inflammatory responses was clarified during long-term pulmonary toxicities. More studies are needed to investigate potential strategies to prevent and rescue severe lung complications.

Dataset Information

Impact of pre-existing interstitial lung abnormal shadow on lung injury development and severity in patients of non-small cell lung cancer treated with osimertinib.

Background

Patients and methods

Results

Conclusions

Publications

Impact of pre-existing interstitial lung abnormal shadow on lung injury development and severity in patients of non-small cell lung cancer treated with osimertinib.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets