Mesothelioma in children and adolescents: the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) contribution

Our plain-English summary of Mesothelioma in children and adolescents: the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) contribution, by D. Orbach, N. André, I.B. Brecht, et al (European Journal of Cancer, 2020).

The study

• Authors: D. Orbach, N. André, I.B. Brecht, R. López Almaraz, T. Ben-Ami, S. Vermersch, M. Carton, C. Virgone, G. Bisogno, D.T. Schneider, V. Bajciova, Y. Reguerre, F. Galateau-Salle, T. Stachowicz-Stencel, R. Dvir, H. Rees, E. Bien, A. Ferrari, M. Ben Arush
• Journal: European Journal of Cancer
• Published: 2020;140:63-70
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Very little is known about the characteristics of mesothelial tumours in the paediatric population. In adults with malignant mesothelioma, the pemetrexed-based regimen with cytoreductive surgery (CRS) is a standard of care in limited tumours, but long-term survival is uncommon.

Material And Methods: The European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT) retrospectively reviewed children, adolescents and young adults (≤21 year) diagnosed with mesothelial tumours treated between 1987 and 2018.

Results: Thirty-three patients were identified, 15 male and 18 female patients. One patient's exposure to asbestos was documented. Primary tumour was mainly in the peritoneum (23 patients). Histology was multicystic mesothelioma of the peritoneum (MCM) (six patients) or malignant mesothelioma (MM) (27 patients). Among MM, the first-line treatment comprised preoperative chemotherapy (14 cases), surgery only (three cases), chemotherapy only (five cases), adjuvant chemotherapy (three cases) or palliative treatment (two cases). The response rate to cisplatin-pemetrexed was 50% (6/12 cases). CRS with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was performed in 19 patients (upfront in three, after neoadjuvant therapy in 12, or after tumour progression in six patients, including three twice). After a median follow-up of 6.7 years (range, 0-20), five-year overall and event-free survivals were 82.3% (95% CI, confidential interval ((CI), 67.8-99.9) and 45.1% (95% CI, 28.4-71.7), respectively. All patients with MCM are alive after surgery (five patients) and CRS-HIPEC (one patient).

Conclusions: Paediatric mesothelioma is exceptional and seems to be different from its adult counterpart with few asbestos exposures, more peritoneal primary, and a better outcome. The cisplatin-pemetrexed regimen showed promising efficacy. Relapses could be salvaged with active therapy including CRS-HIPEC.

Copyright © 2020 Elsevier Ltd. All rights reserved.

In plain English

This retrospective review by the EXPeRT cooperative group covered patients under 21 with mesothelial tumours from registries in 10 countries, treated between 1987 and 2019. Thirty-three patients were identified. Six had multicystic mesothelioma, described as benign, in the peritoneum or the tunica vaginalis; 27 had malignant mesothelioma. Most tumours arose in the peritoneum. One nine-year-old had a familial occupational asbestos exposure; data were missing for five. Six of 12 malignant mesothelioma patients with assessable disease had a partial response to cisplatin-pemetrexed. Six malignant mesothelioma patients died of the disease. For this group, after a median follow-up of 6.7 years, estimated overall survival was 82.3% (95% CI 67.8 to 99.9) and event-free survival 45.1% (95% CI 28.4 to 71.7). The results call these four-year figures, the abstract five-year. Patients with tumour only in the peritoneum fared better than those with chest or multiple sites. All six multicystic patients were alive. The authors concluded that childhood mesothelioma seems different from the adult disease, with few asbestos exposures, more peritoneal tumours and a better outcome. They noted the small retrospective series and varied treatments.

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 multicentre review of patient records (case series) from national and very-rare-tumour registries
• Who was studied: 33 patients under 21 years with mesothelioma (benign or malignant) from registries in 10 countries (France, Italy, Germany, Austria, Spain, Czech Republic, Israel, Poland, United Kingdom, Switzerland), treated between 1987 and 2019. Six had multicystic mesothelioma of the peritoneum and 27 had malignant mesothelioma.
• Exposure: Asbestos exposure was recorded where available. One nine-year-old patient with malignant mesothelioma had a familial occupational asbestos exposure, and data were missing in five cases. Table 1 gives 1 of 24 malignant and 0 of 4 multicystic patients with information. No fiber type is given. The study mainly describes treatments: chemotherapy including cisplatin-pemetrexed, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy (HIPEC).
• Main results:
  • Of the 33 patients, six had multicystic mesothelioma of the peritoneum and 27 had malignant mesothelioma. The main primary site was the peritoneum (26 cases, including three with multiple sites).
  • Despite the group's name, the multicystic tumours arose from the peritoneum or the tunica vaginalis. Table 1 lists five as peritoneal and one under 'Vagina'.
  • Among malignant mesothelioma patients given cisplatin-pemetrexed, six of the 12 with evaluable disease had a partial response. No response was seen with other chemotherapy combinations.
  • Six malignant mesothelioma patients died of disease: 1 of 4 with biphasic and 5 of 21 with epithelioid mesothelioma.
  • In the malignant mesothelioma group, after a median follow-up of 6.7 years (range 0 to 20), overall survival was 82.3% (95% CI 67.8 to 99.9) and event-free survival 45.1% (95% CI 28.4 to 71.7). The results text calls these four-year figures; the abstract calls them five-year figures.
  • The two tunica vaginalis primaries were excluded from this comparison. Malignant mesothelioma patients with an isolated peritoneal primary had better outcomes than those with thoracic or multiple sites. Five-year overall survival was 93.3% (95% CI 81.5 to 100) versus 62.5% (95% CI 36.5 to 100.0), p = 0.0072. Five-year event-free survival was 56.9% (95% CI 38.8 to 83.5) versus 12.5% (95% CI 2.0 to 78.2), p = 0.015.
  • Outcome did not appear statistically different between malignant mesothelioma patients with and without distant metastasis: five-year overall survival 86.3% versus 76.2%, p = 0.13.
  • Among the six patients with multicystic mesothelioma, three peritoneal relapses and one tumour progression occurred during follow-up. All were alive after a median follow-up of 55 months. Five-year event-free survival was 50% and overall survival 100%.
• The authors' conclusion: The authors concluded that paediatric mesothelioma is exceptional and seems to differ from the adult disease, with few asbestos exposures, more peritoneal primaries and a better outcome. They wrote that cisplatin-pemetrexed showed promising efficacy and that relapses could be salvaged with therapy that may include CRS-HIPEC.
• Limitations the authors state:
  • Retrospective design with few patients over a long period
  • Treatment strategies were very heterogeneous
  • Possible recruiting bias, as almost half of all cases were French
  • Some cases had already been published as case reports or small series

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pemetrexed (Alimta), Cytoreductive Surgery, Peritoneum, Histology, Multicystic Mesothelioma (MCM), Chemotherapy, Palliative Care.

Related studies

• 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 perfusion with chemotherapy in children with peritoneal tumor spread: A French nationwide study over 14 years — A. Scalabre, P. Philippe-Chomette, et al. (2018)
• 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)
• Phase II study of first-line bortezomib and cisplatin in malignant pleural mesothelioma and prospective validation of progression free survival rate as a primary end-point for mesothelioma clinical trials (European Organisation for Research and Treatment of Cancer 08052) — M.E. O'Brien, R.M. Gaafar, et al. (2013)
• Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group — K. Mattson, G. Giaccone, et al. (1992)
• Toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric patients with sarcomatosis/carcinomatosis: early experience and phase 1 results — A. Hayes-Jordan, H. Green, et al. (2012)

Browse more research in European Journal of Cancer, or return to medical research.