Extended pleurectomy/decortication and hyperthermic intraoperative intrapleural cisplatin perfusion for malignant pleural mesothelioma

Kenichi Okubo; Hironori Ishibashi; Ryo Wakejima; Shunichi Baba; Ayaka Asakawa; Hiroshi Seshima

doi:10.1016/j.xjon.2023.09.005

Extended pleurectomy/decortication and hyperthermic intraoperative intrapleural cisplatin perfusion for malignant pleural mesothelioma

JTCVS Open. 2023 Sep 14:16:977-986. doi: 10.1016/j.xjon.2023.09.005. eCollection 2023 Dec.

Authors

Kenichi Okubo¹, Hironori Ishibashi¹, Ryo Wakejima¹, Shunichi Baba¹, Ayaka Asakawa¹, Hiroshi Seshima²

Affiliations

¹ Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
² Department of Clinical Engineering, Tokyo Medical and Dental University, Tokyo, Japan.

Abstract

Objective: To evaluate the efficacy of multimodality treatment including extended pleurectomy/decortication (P/D) and hyperthermic intraoperative chemotherapy (HIOC) with cisplatin for malignant pleural mesothelioma (MPM), we investigated the pharmacokinetics of platinum, adverse events after HIOC, and survival outcome.

Methods: Fifty-three patients with pathologically diagnosed MPM (cT1-3N0-1M0, excluding sarcomatoid) underwent an extended P/D and HIOC (cisplatin 80 mg/m² in saline 2 L, 42°C, 60 minutes) since 2011. The protocol includes postoperative 4 cycles of cisplatin and pemetrexed. Platinum concentrations in the perfusate (before and after) and the serum (1, 2, 4, 8, 24, 48, 72 hours after perfusion) were measured in 10 patients. Mortality and morbidity, especially adverse events of renal function, were investigated, and survival and affecting factors were examined.

Results: All patients obtained macroscopic complete resection and pathologic staging revealed as follows: T1/2/3/4: 12/8/23/10, N0/1: 36/17, stage 1A/1B-3A/3B: 12/31/10, respectively. Platinum concentrations in the perfusate indicated that 28% of the dose remained in the pleural cavity, and the maximum concentration in the serum was 0.91 μg/mL. Six patients (11%) showed elevated max-creatinine (>2 mg/dL) postoperatively. Two patients (4%) received renal-replacement therapy, and one was weaned before discharge. There was no 30-day mortality and one in-hospital death (1.9%). Forty-six patients (87%) received multiple cycles of perioperative systemic chemotherapy. Median overall survival (OS) and disease-free survival (DFS) were 52.4 months and 18.7 months. Patents with stage 1A demonstrated a 5-year OS of 67.3% and a median DFS of 67.1 months, and patients with stage 1B-3A demonstrated a 5-year OS of 50.1% and a median DFS of 20.4 months. Univariate analysis showed histological subtype, p-T, p-stage, and multimodality treatment as significant factors affecting OS. Multivariate analysis revealed histology, p-stage, and multimodality as independent.

Conclusions: Extended P/D and HIOC with cisplatin for MPM is acceptable with limited acute kidney injury. This multimodality protocol provides promising favorable survival for stage 1A-3A disease.

Keywords: acute kidney injury; cisplatin; concentration; hyperthermic intraoperative intrapleural chemotherapy; malignant pleural mesothelioma; pleurectomy/decortication; survival.