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

Our plain-English summary of Extended pleurectomy/decortication and hyperthermic intraoperative intrapleural cisplatin perfusion for malignant pleural mesothelioma, by K. Okubo, H. Ishibashi, R. Wakejima, et al (JTCVS Open, 2023).

The study

• Authors: K. Okubo, H. Ishibashi, R. Wakejima, S. Baba, A. Asakawa, H. Seshima
• Journal: JTCVS Open
• Published: 2023;16:977-986
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2023 The Author(s).

In plain English

This retrospective analysis covered 53 consecutive patients with malignant pleural mesothelioma (sarcomatoid type excluded) treated at Tokyo Medical and Dental University, Japan, between 2010 and 2022. All had extended pleurectomy/decortication, then a one-hour, 42 degrees C chest-cavity rinse with cisplatin (80 mg/m2). Four cycles of cisplatin and pemetrexed were planned afterward. The article did not report asbestos exposure. Six patients (11%) had postoperative creatinine above 2 mg/dL, and 2 (4%) needed renal-replacement therapy. No patient died within 30 days, and one died in hospital (1.9%). Median overall survival was 52.4 months and median disease-free survival was 18.7 months. Of 52 surgical survivors, 35 had a recurrence. Five-year overall survival was 67.3% (95% CI 27.7-88.5) in the 12 stage 1A patients and 50.1% (95% CI 27.6-69.0) in the 31 stage 1B-3A patients. Stage 3B patients had a median overall survival of 16.4 months. Histology, stage and completing the treatment program were independently associated with survival. The authors concluded the approach was acceptable with limited acute kidney injury. They noted the small, single-institution design and the difficulty of evaluating any single treatment's effect.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of consecutive patients prospectively enrolled in a single-institution multimodality treatment protocol, with a pharmacokinetic sub-study in 10 patients
• Who was studied: 53 patients with pathologically proven malignant pleural mesothelioma (epithelioid 45, biphasic 8; sarcomatoid excluded), clinically T1-3N0-1 without distant metastasis, treated at Tokyo Medical and Dental University, Japan, 2010 to 2022. Mean age 67.2 years, 47 men (89%). Pathologic stages: 1A 12, 1B-3A 31, 3B 10.
• Exposure: The article does not report asbestos or other exposures. The intervention studied was extended pleurectomy/decortication plus hyperthermic intraoperative intrapleural cisplatin perfusion (80 mg/m2 in 2 L saline at 42 degrees C for 1 hour), with 4 planned postoperative cycles of cisplatin 60 mg/m2 and pemetrexed 500 mg/m2.
• Main results:
  • In the 10-patient pharmacokinetic study, the authors reported that 28% of the platinum in the perfusate remained in the pleural cavity after perfusion.
  • In the same 10 patients, maximum serum total platinum concentration was 0.91 micrograms per mL, at the end of perfusion.
  • Six of 53 patients (11%) had postoperative maximum serum creatinine above 2 mg/dL; one was oliguric and 5 were non-oliguric.
  • Two patients (4%) received renal-replacement therapy. At discharge, 2 patients (4%) still had creatinine above 2 mg/dL, and one of them continued hemodialysis.
  • Acute kidney injury (creatinine above 2) was significantly associated with preoperative serum creatinine (P = .021), but not with operating time or blood loss.
  • There were no deaths within 30 days and one in-hospital death (1.9%), from nonocclusive mesenteric ischemia on postoperative day 70.
  • Other complications included arrhythmia in 17 patients (32%), prolonged air leak over 7 days in 16 (30%), and pneumonia/atelectasis in 12 (23%).
  • 46 of 53 patients (87%) received multiple cycles of perioperative systemic chemotherapy, regarded as completing the multimodality treatment.
  • Among 52 patients who survived surgery, 35 (67%) had a recurrence.
  • Median overall survival in all 53 patients was 52.4 months; 2- and 5-year overall survival were 65.2% and 45.0%.
  • Median disease-free survival in all patients was 18.7 months.
  • Stage 1A patients (n = 12): median disease-free survival 67.1 months; 5-year overall survival 67.3% (95% CI 27.7-88.5).
  • Stage 1B-3A patients (n = 31): median disease-free survival 20.4 months; median overall survival 69.5 months; 5-year overall survival 50.1% (95% CI 27.6-69.0).
  • Stage 3B patients (n = 10): median disease-free survival 9.5 months; median overall survival 16.4 months.
  • In multivariate Cox analysis, histology (epithelioid vs biphasic: HR 4.087, 95% CI 1.469-11.371), pathologic stage (HR 3.286, 95% CI 1.440-7.499) and multimodality treatment were independent significant factors for overall survival.
  • Completing the multimodality treatment had a multivariate hazard ratio of 0.241 (95% CI 0.077-0.751, P = .014) for overall survival.
• The authors' conclusion: The authors concluded that extended pleurectomy/decortication with hyperthermic intraoperative cisplatin is acceptable with limited acute kidney injury. They also concluded that the protocol provides promising favorable survival for stage 1A-3A disease.
• Limitations the authors state:
  • Generalizability is limited because the study comes from a single institution performing a technically demanding procedure.
  • The number of patients was limited, and the stage subgroups were too small for statistical analysis.
  • The single-dose pharmacokinetic study could not quantify outcomes or risk factors.
  • Chemotherapy after recurrence was not consistent over the study period; immune checkpoint inhibitors became available only for later recurrences.
  • The specific effect of a single treatment component is difficult to evaluate in the multimodality setting.

Topics

Medical terms in this study, explained in our Lexicon: Pleurectomy/Decortication (P/D), Cisplatin, Pleural Mesothelioma, Chemotherapy, Sarcomatoid, Pemetrexed (Alimta), Staging, Pleural Cavity.

Related studies

• Interim results of pleurectomy/decortication and intraoperative intrapleural hyperthermic cisplatin perfusion for patients with malignant pleural mesothelioma intolerable to extrapleural pneumonectomy — H. Ishibashi, M. Kobayashi, et al. (2015)
• Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies — M. Ried, T. Potzger, et al. (2013)
• Efficacy of Intraoperative Hypertonic Glucose Solution Administration on Persistent Air Leak After Extended Pleurectomy/Decortication for Malignant Pleural Mesothelioma: A Retrospective Case-Control Study — A. Testori, G. Perroni, et al. (2021)
• Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion — H. Sakaguchi, H. Ishida, et al. (2017)
• Induction Chemotherapy Followed by Pleurectomy Decortication and Hyperthermic Intraoperative Chemotherapy (HITHOC) for Early-Stage Epitheliod Malignant Pleural Mesothelioma-A Prospective Report — S. Bongiolatti, F. Mazzoni, et al. (2021)
• Effect of intraoperative hyperthermic intrathoracic chemotherapy after pleurectomy decortication for treatment of malignant pleural mesothelioma: a comparative study — H.H. Elsayed, H.Y. Sharkawy, et al. (2024)

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