Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection

Our plain-English summary of Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection, by D.J. Sugarbaker, R.R. Gill, B.Y. Yeap, et al (The Journal of Thoracic and Cardiovascular Surgery, 2013).

The study

• Authors: D.J. Sugarbaker, R.R. Gill, B.Y. Yeap, A.S. Wolf, M.C. DaSilva, E.H. Baldini, R. Bueno, W.G. Richards
• Journal: The Journal of Thoracic and Cardiovascular Surgery
• Published: 2013;145(4):955-963
• Cited by: 130 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Local recurrence limits long-term survival in patients with malignant pleural mesothelioma. We investigated whether hyperthermic intraoperative cisplatin chemotherapy lavage affects the interval to recurrence and overall survival among patients with favorable prognostic factors.

Methods: Using a preoperative risk assessment algorithm we had previously developed and validated, we retrospectively identified a cohort of patients treated with cytoreductive surgery from 2001 to 2009. The patients had epithelial histologic findings on biopsy and were characterized as having a low risk of early recurrence and death (ie, tumor volume ≤ 500 cm(3) and were either men with a hemoglobin level of ≥ 13 g/dL or were women). Those patients who had received hyperthermic intraoperative cisplatin chemotherapy were compared with a comparison group of those who had not. Fisher's exact test was used to determine the balance of prognostic factors. The Kaplan-Meier method and log-rank tests were used to estimate and compare the interval to recurrence and overall survival. Cox proportional hazards regression was used for multivariate analysis.

Results: The cohort criteria identified 103 patients: 72 who received hyperthermic intraoperative cisplatin chemotherapy and 31 who did not. The groups were balanced for prognostic factors, except for the use of neoadjuvant chemotherapy (more common in the comparison group). The hyperthermic intraoperative cisplatin chemotherapy group exhibited a significantly longer interval to recurrence (27.1 vs 12.8 months) and overall survival (35.3 vs 22.8 months) than the comparison group. The improved interval to recurrence and overall survival for the hyperthermic intraoperative cisplatin chemotherapy group were particularly evident among the subgroups of patients who had not received hemithoracic radiotherapy and who had pathologic stage N1 or N2 lymph node metastases.

Conclusions: A favorable outcome and minimal incremental morbidity support the incorporation of hyperthermic intraoperative cisplatin chemotherapy into multimodality treatment strategies for patients with low-risk epithelial malignant pleural mesothelioma.

Copyright © 2013. Published by Mosby, Inc.

In plain English

This retrospective study asked whether a heated cisplatin chemotherapy wash of the chest cavity during surgery (HIOC) was linked to longer time before the cancer returned and to longer survival in malignant pleural mesothelioma. It studied a treatment, not asbestos exposure. The authors selected 103 patients who had surgery to remove all visible tumor between 2001 and 2009, whose preoperative biopsies indicated epithelial tumors, and who were judged low-risk before surgery. Of these, 72 received HIOC and 31 did not. Median time to recurrence was 27.1 months with HIOC and 12.8 months without. Median overall survival was 35.3 months with HIOC and 22.8 months without. Differences were seen in patients who had chemotherapy but no radiotherapy and in those with N1 or N2 lymph node spread. They were not statistically significant in patients who also had radiotherapy or had no lymph node spread. More comparison-group patients had chemotherapy before surgery (42% versus 14%). The authors concluded their data suggest, but do not prove, that HIOC improves outcomes in low-risk patients. They noted the sample was small, highly selected and not randomized.

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 cohort study comparing patients who did and did not receive hyperthermic intraoperative cisplatin chemotherapy
• Who was studied: 103 patients with malignant pleural mesothelioma whose preoperative biopsies showed epithelial tumors. All had macroscopic complete resection (extrapleural pneumonectomy or pleurectomy/decortication) between 2001 and 2009. All were judged low-risk before surgery: tumor volume 500 cm3 or less, and either women or men with a hemoglobin level of 13 g/dL or more. 72 received HIOC and 31 formed the comparison group. On final pathologic examination, 16 of the 103 had biphasic tumors.
• Exposure: Treatment, not asbestos exposure: hyperthermic intraoperative cisplatin chemotherapy (HIOC) lavage after tumor removal, cisplatin 175 to 225 mg/m2 for a 1-hour lavage at 42 degrees C, with sodium thiosulfate rescue and/or amifostine protection. This was compared with surgery without HIOC.
• Main results:
  • Median interval to recurrence was 27.1 months in the HIOC group versus 12.8 months in the comparison group (P = .0084).
  • Median overall survival was 35.3 months in the HIOC group versus 22.8 months in the comparison group (P = .026).
  • Among patients who received chemotherapy but no radiotherapy, the interval to recurrence was 26.3 months with HIOC versus 10 months without (P = .013). Median overall survival in this subgroup was 51.1 versus 20.6 months (P = .0042).
  • Among patients who received radiotherapy in addition to chemotherapy, overall survival was not significantly different between the HIOC and comparison groups (36.4 vs 31.2 months; P = .15). The interval to recurrence also did not differ significantly in this subgroup (P = .14).
  • Among patients with pathologic N1 or N2 lymph node disease, the interval to recurrence was 23.5 months with HIOC versus 11.1 months without (P = .0012). Median overall survival in this subgroup was 33.1 versus 17.4 months (P = .018).
  • Among patients with pathologic N0 disease, overall survival did not differ between the groups (36.4 vs 40.3 months; P = .71).
  • In multivariate analysis, the reference group was patients who received neither HIOC nor adjuvant therapy. Against that group, HIOC with adjuvant therapy had a hazard ratio for death of 0.28 (95% CI 0.12-0.65). HIOC without adjuvant therapy had 0.64 (0.25-1.65), and adjuvant therapy without HIOC had 0.48 (0.20-1.13).
  • The groups were not balanced for chemotherapy before surgery: 42% of the comparison group had received it versus 14% of the HIOC group (P = .0037).
  • Although all patients had epithelial tumors on preoperative biopsy, final pathologic analysis showed biphasic tumors in 9 HIOC patients (13%) and 7 comparison patients (23%).
  • All 3 postoperative deaths occurred in the HIOC group (not statistically significant). None was thought to be related to HIOC.
• The authors' conclusion: The authors concluded that their data suggest, but do not prove, that HIOC improves the outcomes of low-risk patients with malignant pleural mesothelioma.
• Limitations the authors state:
  • The study was retrospective and small, particularly the comparison group.
  • The cohort was highly selected, and using patients who did not receive HIOC as the comparison group introduced inherent bias.
  • The comparison group included significantly more patients who had received chemotherapy before surgery.
  • The HIOC group included patients treated on and off various protocols.
  • Including adjuvant therapy in the multivariate analysis was subject to guarantee time bias, which might have overestimated its influence on survival.
  • The subgroup of patients who had extrapleural pneumonectomy with radiotherapy was too small to draw definitive conclusions.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Cisplatin, Chemotherapy, Pleural Mesothelioma, Overall Survival, Cytoreductive Surgery, Biopsy, Multivariate Analysis, Neoadjuvant Chemotherapy.

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• 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)
• Anesthetic management and renal function in pediatric patients undergoing cytoreductive surgery with continuous hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin — P. Owusu-Agyemang, R. Arunkumar, et al. (2012)
• Role of hyperthermic intraoperative peritoneal chemotherapy in the management of peritoneal metastases — D. Elias, D. Goéré, et al. (2014)
• Iterative procedures combining cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for isolated peritoneal recurrence — M. Vaira, M. Robella, et al. (2014)
• Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) — G.H.C. Tan, C.S. Chia, et al. (2018)

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