Lymph nodes rather than pleural metabolic activity in ¹⁸F-FDG PET/CT correlates with malignant pleural effusion recurrence in advanced non-small cell lung cancer

Background: Frequently recurrent malignant pleural effusion (MPE) significantly hampers the life quality of advanced non-small cell lung cancer (NSCLC) patients. We aimed to explore the effects of progression patterns and local intervention on MPE recurrence and apply fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) to establish a predictive model for MPE recurrence in NSCLC.

Methods: We retrospectively recruited two cohorts of patients including treatment-naïve NSCLC diagnosed with MPE at the onset and receiving PET/CT scanning, as well as those with MPE and undergoing first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Pleural maximum standardized uptake value (SUV_max), metabolic tumor burden (MTV), total lesion glycolysis (TLG), and uptake patterns as well as SUV_max of lymph nodes (LN) were extracted. The primary outcome was MPE recurrence defined as re-accumulation of cytologically proven ipsilateral MPE. Step-wise multivariate Cox regression was used to identify candidate variables. Cox regression analysis and random survival forest were applied to establish models.

Results: A total of 148 treatment-naïve patients with EGFR-TKI treatment and MPE were recruited during the median follow-up period of 683 days, with 69 (46.6%) and 35 (23.6%) witnessing MPE recurrence at least once and twice. Intrapleural perfusion therapy at first recurrence was a protective factor for the second MPE recurrence (P=0.006), while intrapleural perfusion therapy at baseline could not benefit the first MPE recurrence (P=0.14). Conversely, prior systemic progression indicative of the change of systemic treatment was a protective factor for time to the first MPE recurrence (P<0.001); instead, the change of systemic treatment at the first MPE recurrence was not associated with second MPE recurrence (P=0.53). In another cohort with treatment-naïve NSCLC patients with MPE and PET/CT scanning, 103 patients regardless of the actionable mutation status were recruited during the median follow-up period of 304 days. Multivariate analysis suggested that the LN SUV_max >4.50 g/mL [hazard ratio (HR), 2.54; P=0.01], female gender (HR, 0.40; P=0.01), bone metastases (HR, 3.16; P=0.001), and systemic treatment (targeted therapy vs. chemotherapy: HR, 0.32; P=0.002; immunotherapy therapy vs. chemotherapy: HR, 0.99; P=0.97) could collectively indicate MPE recurrence with an optimal 300-day area under the curve (AUC) of 0.83. For patients with actionable mutation, LN SUV_max >4.50 g/mL (P=0.02) could forecast MPE recurrence independently.

Conclusions: In summary, LN rather than pleural metabolic activity or uptake patterns could predict MPE recurrence for patients with or without targeted therapy. We should re-consider the application of intrapleural perfusion treatment for first-onset MPE and prompt it more at the moment of recurrent MPE. Promisingly, we could probably apply the non-invasive tool to identify the risk factors for MPE recurrence.