Effect of hyperthermic intrathoracic chemotherapy (HITHOC) on the malignant pleural effusion: A systematic review and meta-analysis

Abstract

Background: Although hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely used to treat malignant ascites or as a preventive strategy for microscopic carcinomatosis following surgical resection of abdominal tumors, application of hyperthermic intrathoracic chemotherapy (HITHOC) in the treatment of malignant pleural effusion is limited. The objective of the current study was to conduct a systematic review and meta-analysis on the application of HITHOC in the palliative treatment of malignant pleural effusion.

Methods: After thorough searching of online databases, total 27 articles were included into qualitative systematic review and 5 of them were used to conduct qualitative meta-analysis.

Results: It was found that most of HITHOC was used in combination of cytoreductive surgery (CRS) including pleurectomy/decortication or after surgical resection of primary tumors, which mainly were lung cancer, thymoma or thymic carcinoma, breast cancer, and ovarian cancer. Patients who received HITHOC had significantly longer median survival length compared to the patients without HITHOC (Hedges g = 0.763, P < 0.001). In addition, HITHOC therapy was favored (Hedges g = 0.848, P < 0.001) in terms of median survival length, tumor-free survival rate, with tumor survival rate or Karnofsky performance status (KPS) scale.

Conclusion: HITHOC is a safe and effective therapy in controlling pleural effusion and increasing patient's survival rate.

Figure 1

Flow diagram of literature search and eligible publication selection.

Figure 2

Forest plot for median survival length. A fixed effect model was used due to nonsignificant heterogeneity of publications (I² = 0.01%, P = 0.99). Effect size was assessed by Hedges g and 95% CI, and the median survival length was in favors HITHOC (Hedges g = 0.763, P < 0.001). Ba ^#1: patients treated with B-ultrasound-guided intrapleural hyperthermic perfusion with 48 °C distilled water; Ba ^#2: patients treated with B-ultrasound-guided intrapleural hyperthermic perfusion with 45 °C physiologic saline solution plus cisplatin; Ba ^#3: patients without HIPTHOC. Isilk ^#1: patients treated with HITHOC following surgical intervention; Isilk ^#2: patients treated with talc pleurodesis followed by systemic treatment; Isilk ^#3: patients treated with pleurectomy/decortication followed by systemic treatment. Zhang ^#1: patients were EGFR positive and treated with HITHOC; Zhang ^#2: patients were EGFR negative but treated with HITHOC; Zhang ^#3: patients were not treated with HITHOC. EGFR = epithermal growth factor receptor positive, HITHOC = hyperthermic intrathoracic chemotherapy.

Figure 3

Forest plot for efficacy of HITHOC. A fixed effect model was used due to significant heterogeneity of publications (I² = 31.23%, P = 0.179). Effect size was assessed by Hedges g and 95% CI, and the efficacy of the treatment was in favor of HITHOC therapy (Hedges g = 0.848, P < 0.001). Matsuzaki studies: response rate and apoptosis rate comparison. Isilk study: comparison of 1-year overall survival rate. Zhang study: comparison of TFS rate and WTS rate. HITHOC = hyperthermic intrathoracic chemotherapy, TFS = tumor free survival, WTS = with tumor survival.