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Clinical course of asymptomatic malignant pleural effusion in non-small cell lung cancer patients: A multicenter retrospective study.

ABSTRACT:

Abstract

The British Thoracic Society guidelines recommend observation for patients with asymptomatic malignant pleural effusion (MPE). However, asymptomatic MPE can become symptomatic. This study examined the clinical course of asymptomatic MPE in patients with non-small cell lung cancer (NSCLC), including the incidence and timing of symptom development of asymptomatic MPE and the associated factors.Retrospective data of 4822 NSCLC patients between January 2012 and December 2017 were reviewed. Symptom development of asymptomatic MPE was defined as the development of symptoms requiring additional treatment, such as insertion of a chest tube, within 1 year in patients who lacked MPE symptoms at the time of diagnosis. Clinical information, pathological parameters, and radiological characteristics were reviewed. Patient data up to 1 year from the initial diagnosis were reviewed.Of 113 patients with asymptomatic MPE, 46 (41%) became symptomatic within 1 year despite appropriate anticancer treatment. The median time to symptom development was 4 months, and 38 patients (83%) developed symptoms within 6 months. Multivariate logistic regression showed that female sex (odds ratio [OR], 0.256; 95% confidence interval [CI], 0.101-0.649; P = .004) and the depth of pleural effusion on initial computed tomography (CT) (OR, 0.957; 95% CI, 0.932-0.982; P = .001) were independently associated with symptom development of asymptomatic MPE.A fraction of 41% of patients with asymptomatic MPE became symptomatic within 1 year. Female sex and larger MPE on initial CT were independently associated with symptom development of asymptomatic MPE.

SUBMITTER: Roh J

PROVIDER: S-EPMC8133234 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNon-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10-12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively.MethodsGenotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing (WES), and patients and xenograft-bearing mice received targeted treatment (crizotinib or osimertinib) accordingly. Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size. Finally, the pathology of patients biopsies and xenograft tumors were compared histologically.ResultsThe histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients. WES showed that the genotypes of the xenograft and patient tumors were similar (an echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) gene fusion (patient/xenograft: CTC15035EML4-ALK) and EGFR L858R and T790M mutations (patient/xenograft: CTC15063EGFR L858R, T790M)). After continuous crizotinib or osimertinib treatment, WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035EML4-ALK xenograft, while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B (BRAF) G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha (PIK3C2A) A86fs frame shift mutations led to osimertinib resistance in the CTC15063EGFR L858R, T790M xenografts.ConclusionsWe successfully developed a new method of generating drug resistance xenograft models from liquid biopsies using microfluidic technology, which might be a useful tool to investigate the mechanisms of drug resistance in NSCLC.

Project description:Simple Summary Minimal data exists on pleural effusion (PE) for non-small cell lung cancer (NSCLC) patients undergoing combined ICI and chemotherapy. We retrospectively investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival and overall survival than those without PE. In addition, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. In conclusion, PE was associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy. Abstract Objectives: Combined immune checkpoint inhibitor (ICI) therapy and chemotherapy has become the standard treatment for advanced non-small-cell lung cancer (NSCLC). Pleural effusion (PE) is associated with poor outcomes among patients with NSCLC undergoing chemotherapy. However, minimal data exists on PE for patients undergoing combined ICI and chemotherapy. Therefore, we investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. Methods: We identified patients with advanced NSCLC undergoing chemotherapy and ICI therapy from the Okayama Lung Cancer Study Group–Immune Chemotherapy Database (OLCSG–ICD) between December 2018 and December 2020; the OLCSG–ICD includes the clinical data of patients with advanced NSCLC from 13 institutions. Then, we analyzed the treatment outcomes based on the presence of PE. Results: We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without PE (median PFS: 6.2 months versus 9.1 months; p < 0.001; median OS: 16.4 months versus 27.7 months; p < 0.001). The negative effect of PE differed based on the patient’s programmed cell death-ligand 1 (PD-L1) expression status; with the effect being more evident in patients with high PD-L1 expression. In addition, PFS and OS did not differ between patients who did and did not undergo bevacizumab treatment; thus, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. Conclusion: PE is associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy.

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Clinical course of asymptomatic malignant pleural effusion in non-small cell lung cancer patients: A multicenter retrospective study.

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