Toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric patients with sarcomatosis/carcinomatosis: early experience and phase 1 results

Our plain-English summary of Toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric patients with sarcomatosis/carcinomatosis: early experience and phase 1 results, by A. Hayes-Jordan, H. Green, J. Ludwig, et al (Pediatric Blood & Cancer, 2012).

The study

• Authors: A. Hayes-Jordan, H. Green, J. Ludwig, P. Anderson
• Journal: Pediatric Blood & Cancer
• Published: 2012;59(2):395-7
• Cited by: 41 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Intra-abdominal metastasis is a rare form of tumor dissemination in children. Complete surgical resection is usually deemed impossible. Children are frequently offered palliative care only. We adopted an aggressive approach for these cases which includes removal of dozens to hundreds of tumor nodules followed by perfusion of the abdominal cavity with hyperthermic chemotherapy (HIPEC) with a curative intent.

Methods: We evaluated toxicity in 23 children and young adults undergoing 27 HIPEC procedures using cisplatin. Disease diagnoses included rhabdomyosarcoma (RMS), non-RMS soft tissue sarcoma, (NRSTS), desmoplastic small round cell tumor, (DSRCT), mesothelioma, Wilms tumor, melanomatosis, and adenocarcinoma. Patients underwent cytoreductive surgery followed by cisplatin at 40.5-41 °C, for 90 minutes. A subset of these patients was enrolled on our phase 1 study and as part of dose escalation cohort received 150 mg/m(2) of cisplatin. All toxicities were recorded.

Results: Maximum tolerated dose was 100 mg/m(2). Dose limiting toxicity was grade 3 renal failure. In five of 27, 18% had grade 3 or higher renal failure. One patient developed a subclinical decrease in hearing and there were 2 grade 3 hematologic toxicities, 2 grade 3 hepatic toxicities, and one grade 3 ileus. One patient suffered grade3 cardiotoxicity. There were no operative/perioperative mortalities. Surgical complications occurred in 5/27 (18%) of patients. With a follow-up of 6-60 months, seven patients (26%) had no recurrence.

Conclusions: HIPEC is reasonably tolerated in pediatric patients with extensive abdominal metastasis. More study is needed to determine for which histologies HIPEC is most efficacious.

Copyright © 2012 Wiley Periodicals, Inc.

In plain English

This article from the University of Texas M.D. Anderson Cancer Center reported side effects in 23 patients aged 3 to 21 years who had 27 procedures. Surgeons removed abdominal tumors and then bathed the abdomen in heated cisplatin chemotherapy (HIPEC). Complete removal, with no disease left, was achieved in 23 of 27 (85%). Diagnoses included desmoplastic small round cell tumor (13) and mesothelioma (5). The first patients were treated in a phase 1 dose-escalation trial. At 150 mg/m2, two patients had grade III kidney toxicity, so the dose was reduced to 100 mg/m2. In the article's main text, 2 of 27 procedures (7.4%) were followed by kidney insufficiency or failure, and one patient needed dialysis for 3 weeks. One patient had a serious heart problem. No patient died during or around surgery. Surgical complications, mostly wound infections, occurred in 7 of 27 (26%). Nine (9/27) relapsed in the abdomen. The article's abstract gives different figures for kidney failure and complications. The authors concluded that HIPEC was reasonably well tolerated and that its effectiveness needs study in more patients.

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: Report of side effects (toxicity) in pediatric patients treated with HIPEC. A first group was treated on a phase 1 dose-escalation trial (3 by 3 design), and a second group was treated as novel therapy under the same protocol. The results of both groups were combined.
• Who was studied: 23 children and young adults, aged 3 to 21 years, who underwent 27 HIPEC procedures at the University of Texas M.D. Anderson Cancer Center, Houston. Inclusion required extensive disease limited to the abdominal cavity. Diagnoses listed: desmoplastic small round cell tumor (13), mesothelioma (5), rhabdomyosarcoma (2), Wilms tumor (2), and one each of melanoma, liposarcoma, neurofibrosarcoma, pancreatic carcinoma and ovarian adenocarcinoma. Two patients, both with mesothelioma, had HIPEC twice. 60% were male.
• Exposure: Cytoreductive surgery followed by closed-technique hyperthermic intraperitoneal cisplatin for 90 minutes at about 40.5 to 41 °C. The phase 1 trial tested doses of 100 mg/m2 and 150 mg/m2. Intravenous sodium thiosulfate was given afterwards. The study does not concern asbestos exposure.
• Main results:
  • In the phase 1 trial, two patients given 150 mg/m2 had grade III nephrotoxicity, so the dose was reduced. The maximum tolerated dose was 100 mg/m2. The dose-limiting toxicity was grade 3 renal failure, which was non-oliguric in all patients.
  • Overall, renal insufficiency or failure followed 7.4% (2/27) of HIPEC procedures.
  • In 12 patients, creatinine (a kidney blood test) rose more than 50% and then returned to baseline. One patient needed temporary hemodialysis for 3 weeks.
  • Other side effects: 6 grade 1 and 2 hematologic toxicities, 2 grade 3 hematologic toxicities, 2 grade 3 hepatic toxicities, one grade 3 ileus, and one subclinical decrease in hearing.
  • One patient, a 16-year-old male, had grade 3 cardiotoxicity. He had no symptoms, but a screening echocardiogram showed an ejection fraction of 29%. It resolved with beta blockers.
  • There were no operative or peri-operative deaths.
  • Surgical complications occurred in 7/27 (26%) of patients. Most were wound infections, and two small bowel obstructions required readmission. The average time of surgery was 11 hours.
  • Complete surgical resection with no disease left at the end of HIPEC was achieved in 85% (23/27).
  • 33% (9/27) relapsed in the abdomen. 26% had a sustained complete response without recurrence, from 1 year to 4 years after HIPEC.
• The authors' conclusion: The authors concluded that HIPEC is reasonably well tolerated in pediatric patients with diffuse metastatic abdominal disease, mostly sarcomatosis. They also concluded that its efficacy needs further evaluation in a larger cohort.
• Limitations the authors state:
  • The authors state that efficacy needs further evaluation with a larger group of patients.

Topics

Medical terms in this study, explained in our Lexicon: HIPEC, Metastasis, Surgical Resection, Palliative Care, Chemotherapy, Cisplatin, Sarcoma, Desmoplastic Small Round Cell Tumor.

Related studies

• 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)
• 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)
• 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)
• Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) — G.H.C. Tan, C.S. Chia, et al. (2018)
• Peritoneal carcinomatosis from unusual cancer origins: Is there a role for hyperthermic intraperitoneal chemotherapy? — C. Honoré, D. Goéré, et al. (2016)
• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)

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