A Review of the Use of Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignancy in Pediatric Patients

Our plain-English summary of A Review of the Use of Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignancy in Pediatric Patients, by D.J. Byrwa, C.J. Twist, J. Skitzki, et al (Cancers, 2023).

The study

• Authors: D.J. Byrwa, C.J. Twist, J. Skitzki, E. Repasky, P.B. Ham, A. Gupta
• Journal: Cancers
• Published: 2023;15(10)
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Hyperthermic intraperitoneal chemotherapy (HIPEC) can directly target microscopic peritoneal disease, has achieved regular consideration in the treatment of several adult cancer types, and is more recently being studied in pediatrics. This review paper provides an overview of the use of this modality in pediatrics in order to identify medication choice, discuss post-operative morbidity and mortality, and evaluate impact on overall survival. Four databases were searched including Scopus, PubMed, Embase, and CINAHL and ultimately 37 papers documenting the use of this modality comprising 264 pediatric patients were included. Malignancies treated include desmoplastic small round cell tumor, rhabdomyosarcoma, angiosarcoma, colorectal carcinoma, and mesothelioma, with several rarer tumor types. Cisplatin was the most commonly used drug for HIPEC at varying concentrations for 30-90 min in duration at temperatures of approximately 41-42 °C. Reported toxicities were generally self-limited and there was no post-operative mortality. The impact on overall survival versus systemic chemotherapy and debulking surgery is uncertain due to lack of clinical trials and very small sample size across tumor subsets and the overall pediatric population. The relationship between degree of tumor burden and extent of surgical debulking needs to be further clarified. Future directions include prospective clinical trials, establishment of patient databases to facilitate standardization of HIPEC in pediatric patients, and additional approaches to optimize HIPEC.

In plain English

This article was a review of published reports, not a new patient study. The authors searched four databases in February 2023 for reports of hyperthermic intraperitoneal chemotherapy (HIPEC) in children and adolescents. HIPEC means circulating heated chemotherapy inside the abdomen during surgery. The authors said the review was not formally a systematic review. They included 37 papers covering 264 pediatric patients. The commonest cancers were desmoplastic small round cell tumor (87), mesothelioma (64) and rhabdomyosarcoma (30). Cisplatin was used most often, usually for 30 to 90 minutes at about 41 to 42 degrees Celsius. Reported side effects were generally self-limited, most often low blood counts. No deaths within 30 days of surgery were reported. No evidence of disease was noted in 33% at last follow-up, which varied in length. The authors concluded that HIPEC was generally tolerated. They also concluded that its effect on survival compared with chemotherapy and surgery was uncertain, citing a lack of clinical trials and small numbers; the pediatric evidence came from non-randomized trials, case series and case reports, with no multicenter randomized trials. The article did not examine asbestos exposure.

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: Literature review of published reports on HIPEC in pediatric patients; the authors state it is not officially a systematic review
• Who was studied: 264 pediatric patients described in 37 published papers. The papers were found by searching Scopus, PubMed, Embase and CINAHL in February 2023, with no limit on publication date. Cancers included desmoplastic small round cell tumor (87 patients), mesothelioma (64), rhabdomyosarcoma (30), primary ovarian tumors (19), colon carcinoma (11) and others.
• Exposure: Not an asbestos exposure study. The review covered a treatment: hyperthermic intraperitoneal chemotherapy (HIPEC), usually combined with cytoreductive surgery, given to children with cancer that had spread within the abdomen.
• Main results:
  • Across the reviewed reports, cisplatin (alone or with other drugs) was the most commonly used HIPEC drug. It was given for 30 to 90 minutes at about 41 to 42 degrees Celsius, with slight variation.
  • Reported toxicities and complications in the pediatric patients were generally self-limited. The most common were pancytopenia, anemia or thrombocytopenia (low blood counts).
  • None of the pediatric reports reviewed recorded a post-operative death, defined as a death within 30 days of the procedure.
  • No evidence of disease was noted in 33% of the 264 patients at last follow-up. The length of follow-up varied across the papers.
  • Among patients still alive at last follow-up, median follow-up was 19.5 months (standard deviation 24.1 months).
  • The largest pediatric mesothelioma series the review describes came from the European Cooperative Study Group for Pediatric Rare Tumors: 27 patients under 18 with malignant mesothelioma, 19 of whom received cytoreductive surgery with HIPEC. It reported a median follow-up of 6.7 years and a 5-year overall survival of 82.3%. The review does not make clear whether the 82.3% figure applies to all 27 patients or only to the 19. The authors note that all pediatric mesothelioma HIPEC studies were retrospective.
• The authors' conclusion: The authors concluded that HIPEC, most commonly with cisplatin, was generally tolerated, with short-term post-operative complications. They judged its effect on overall survival compared with systemic chemotherapy and debulking surgery to be uncertain, because of a lack of clinical trials and small sample sizes. They called for long-term outcome data and for prospective, multi-institutional randomized trials.
• Limitations the authors state:
  • The pediatric evidence was limited to single-arm, single-institution non-randomized trials, case series and case reports. There were no multicenter randomized controlled trials in this population.
  • The tumors are rare, and the surgery requires specialized cancer centers.
  • The reported patients were likely a highly selected group.
  • The source papers did not consistently report degree of tumor burden.
  • Some patients also received radiotherapy and stem cell transplant, which may have affected illness and survival.
  • Length of follow-up varied across the papers.
  • The review was not a formal systematic review: not all sections of the PRISMA 2020 checklist were completed.

Topics

Medical terms in this study, explained in our Lexicon: HIPEC, Overall Survival, Desmoplastic Small Round Cell Tumor, Carcinoma, Mesothelioma, Cisplatin, Chemotherapy, Cytoreductive Surgery.

Related studies

• Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in pediatric patients with peritoneal mesothelioma: a single institution experience and long term follow up — P. Malekzadeh, M. Good, et al. (2021)
• What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: A 25-year experience with 1,125 procedures — G. Passot, D. Vaudoyer, et al. (2016)
• The results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1200 patients with peritoneal malignancy — B. Moran, T. Cecil, et al. (2015)
• Outcomes of repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal surface malignancy — K.I. Votanopoulos, C. Ihemelandu, et al. (2012)
• Evaluation of the cost-effectiveness of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (peritonectomy) at the St George Hospital peritoneal surface malignancy program — T.C. Chua, S. Martin, et al. (2010)
• Long-term outcomes and survival analysis of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei at a newly established peritoneal malignancy centre in Japan — H. Yano, Y. Gohda, et al. (2024)

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