Adequate nephroprotection reduces renal complications after hyperthermic intrathoracic chemotherapy

Our plain-English summary of Adequate nephroprotection reduces renal complications after hyperthermic intrathoracic chemotherapy, by T. Markowiak, N. Kerner, R. Neu, et al (Journal of Surgical Oncology, 2019).

The study

• Authors: T. Markowiak, N. Kerner, R. Neu, T. Potzger, C. Großer, F. Zeman, H.S. Hofmann, M. Ried
• Journal: Journal of Surgical Oncology
• Published: 2019;120(7):1220-1226
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background And Objectives: Hyperthermic intrathoracic chemotherapy (HITOC) is used for the treatment of malignant pleural tumors. Although HITOC proved to be safe, postoperative renal failure due to nephrotoxicity of intrapleural cisplatin remains a concern.

Methods: This single-center study was performed retrospectively in patients who underwent pleural tumor resection and HITOC between September 2008 and December 2018.

Results: A total of 84 patients (female n = 33; 39.3%) with malignant pleural tumors underwent surgical cytoreduction with subsequent HITOC (60 minutes; 42°C). During the study period, we gradually increased the dosage of cisplatin (100-150 mg/m2 BSA n = 36; 175 mg/m2 BSA n = 2) and finally added doxorubicin (cisplatin 175 mg/m2 BSA/doxorubicin 65 mg; n = 46). All patients had perioperative fluid balancing. The last 54 (64.3%) patients also received perioperative cytoprotection. Overall 29 patients (34.5%) experienced renal insufficiency. Despite higher cisplatin concentrations, patients with cytoprotection showed significantly lower postoperative serum creatinine levels after 1 week (P = .006) and at discharge (P = .020). Also, they showed less intermediate and severe renal insufficiencies (5.6% vs 13.3%).

Conclusions: Adequate perioperative fluid management and cytoprotection seem to be effective in protecting renal function. This allows the administration of higher intracavitary cisplatin doses without raising the rate of renal insufficiencies.

© 2019 Wiley Periodicals, Inc.

In plain English

This retrospective single-center study reviewed 84 patients with malignant pleural tumors, about half with malignant pleural mesothelioma. Between September 2008 and December 2018 they had tumor-removal surgery followed by heated chemotherapy circulated through the chest (HITOC). The article does not discuss asbestos. It examined kidney damage from the drug cisplatin. All patients received extra fluids. From June 2013, 54 patients also received the kidney-protecting drugs amifostine and sodium thiosulfate, and most of these patients got a higher cisplatin dose with doxorubicin added. Overall, 29 patients (34.5%) developed kidney impairment, mostly mild. The overall rate did not differ significantly between patients with and without the protective drugs (37% of 54 versus 30% of 30). Moderate or severe impairment was less common with the protective drugs (5.6% versus 13.3%). Blood creatinine, a kidney marker, was significantly lower in these patients one week after surgery and at discharge. Three patients needed temporary dialysis. The authors concluded that the protective drugs seem effective. They noted the study was retrospective, and that cisplatin doses rose at the same time the protective drugs were introduced.

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 single-center study
• Who was studied: 84 patients (33 female, 39.3%) with malignant pleural tumors who had pleural tumor resection followed by HITOC between September 2008 and December 2018. Of these, 43 (51.2%) had malignant pleural mesothelioma and 32 (38.1%) had thymoma. The authors are from thoracic surgery departments in Regensburg, Germany.
• Exposure: This was not an asbestos exposure study. The exposures studied were intrathoracic cisplatin dose and kidney protection. Cisplatin was given at 100 to 150 mg/m2 body surface area in 36 patients, and at 175 mg/m2 in 48 patients (46 of them with doxorubicin 65 mg). All patients had perioperative fluids. From June 2013, 54 patients also received amifostine and sodium thiosulfate.
• Main results:
  • Across all 84 patients, 29 (34.5%) had postoperative kidney impairment of grades 1 to 3: 22 grade 1, 4 grade 2 and 3 grade 3.
  • There was no significant difference in the occurrence of kidney impairment by cisplatin dose (P = .79) or by use of cytoprotection (P = .52). Table 2 shows 20 of 54 (37%) in the cytoprotection group and 9 of 30 (30%) in the hydration-only group.
  • Moderate or severe (grade 2 and 3) kidney impairment occurred in 5.6% of patients with cytoprotection and in 13.3% of patients with hydration only.
  • After adjustment for preoperative levels, serum creatinine was significantly lower with cytoprotection than with hydration only. At 1 week it was 0.85 (95% CI 0.67 to 1.04) versus 1.3 (1.05 to 1.55), P = .006. At discharge it was 0.82 (0.68 to 0.96) versus 1.11 (0.91 to 1.3), P = .020. On day 1 it was higher with cytoprotection: 1.13 versus 0.95, P = .018.
  • Patients receiving cisplatin 175 mg/m2 had significantly lower creatinine than those receiving lower doses, both at 1 week (P = .001) and at discharge (P = .001).
  • Creatinine levels were significantly higher after extrapleural pneumonectomy than after lung-sparing pleurectomy/decortication or extended pleurectomy/decortication.
  • In a logistic regression model, cytoprotection (P = .043) and induction therapy (P = .033) had significant effects on postoperative kidney impairment. Cisplatin dose (P = .131) and type of surgery (P = .52) did not.
  • Temporary dialysis was needed in 3 patients (3.6%), two of them early patients without cytoprotection. No patient needed chronic dialysis.
• The authors' conclusion: The authors concluded that, alongside fluid management, amifostine and sodium thiosulfate seem to be effective in protecting kidney function from cisplatin. In their view this allows higher intracavitary cisplatin doses without raising the rate of kidney impairment. They added that special caution is still needed in patients with raised creatinine or known kidney impairment before surgery.
• Limitations the authors state:
  • The study had a single-center design in selected patients and was retrospective.
  • There was no control group of patients without HITOC.
  • The cisplatin dose was increased at the same time cytoprotection was introduced, so the measured effect of cytoprotection was probably attenuated.
  • The patients were a heterogeneous group with different tumor types and treatment algorithms.

Topics

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

Medical terms in this study, explained in our Lexicon: Intrathoracic, Chemotherapy, Nephrotoxicity, Cisplatin, Cytoreductive Surgery, Doxorubicin.

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• 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)
• Outcomes of Cytoreductive Surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients older than 70 years; survival benefit at considerable morbidity and mortality — K.I. Votanopoulos, N.A. Newman, et al. (2013)
• Cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for children, adolescents, and young adults: the first 50 cases — A. Hayes-Jordan, H. Green, et al. (2015)
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