Childhood Mesothelioma Treatment (PDQ®): Treatment - Health Professional Information [NCI]

Incidence, Risk Factors, and Clinical Presentation

Mesothelioma is extremely rare in children and adolescents, with only 2% to 5% of patients presenting during the first two decades of life.[1] Fewer than 300 cases in children have been reported.[2]

In adults, increased mesothelioma risk is associated with inherited BAP1 mutations, exposures to asbestos, and exposures to radiation therapy during previous cancer treatments. These risk factors are rare in pediatric patients, and there are limited data that address cancer risk in children with asbestos exposures. The amount of radiation exposure required to develop cancer is also unknown.[3,4,5,6,7,8]

Mesothelioma may present in the thoracic/pleural region or in the peritoneum. These presentations have different clinical courses and prognoses. This cancer can involve the membranous coverings of the lung, the heart, or the abdominal organs.[9,10,11]; [12][Level of evidence C1] Mesothelioma can spread onto organ surfaces without invading far into the underlying tissue. This cancer may also spread to regional or distant lymph nodes.

Benign and malignant mesotheliomas cannot be differentiated using histological criteria. Benign mesotheliomas are exceedingly rare and often occur in the peritoneal cavity. A poor prognosis is associated with mesotheliomas that are diffuse and invasive or with mesotheliomas that recur.

References:

1. Nagata S, Nakanishi R: Malignant pleural mesothelioma with cavity formation in a 16-year-old boy. Chest 127 (2): 655-7, 2005.
2. Rosas-Salazar C, Gunawardena SW, Spahr JE: Malignant pleural mesothelioma in a child with ataxia-telangiectasia. Pediatr Pulmonol 48 (1): 94-7, 2013.
3. Orbach D, André N, Brecht IB, et al.: Mesothelioma in children and adolescents: the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) contribution. Eur J Cancer 140: 63-70, 2020.
4. Tsao AS, Wistuba I, Roth JA, et al.: Malignant pleural mesothelioma. J Clin Oncol 27 (12): 2081-90, 2009.
5. Carbone M, Ferris LK, Baumann F, et al.: BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs. J Transl Med 10: 179, 2012.
6. Janes SM, Alrifai D, Fennell DA: Perspectives on the Treatment of Malignant Pleural Mesothelioma. N Engl J Med 385 (13): 1207-1218, 2021.
7. Hofmann J, Mintzer D, Warhol MJ: Malignant mesothelioma following radiation therapy. Am J Med 97 (4): 379-82, 1994.
8. Pappo AS, Santana VM, Furman WL, et al.: Post-irradiation malignant mesothelioma. Cancer 79 (1): 192-3, 1997.
9. Kelsey A: Mesothelioma in childhood. Pediatr Hematol Oncol 11 (5): 461-2, 1994 Sep-Oct.
10. Moran CA, Albores-Saavedra J, Suster S: Primary peritoneal mesotheliomas in children: a clinicopathological and immunohistochemical study of eight cases. Histopathology 52 (7): 824-30, 2008.
11. Cioffredi LA, Jänne PA, Jackman DM: Treatment of peritoneal mesothelioma in pediatric patients. Pediatr Blood Cancer 52 (1): 127-9, 2009.
12. Vermersch S, Arnaud A, Orbach D, et al.: Multicystic and diffuse malignant peritoneal mesothelioma in children. Pediatr Blood Cancer 67 (6): e28286, 2020.

Genomic Alterations

Malignant mesotheliomas found in children, adolescents, and young adults are not often associated with asbestos exposures. This differs from most malignant mesotheliomas seen in adults. Recurring ALK gene fusions have been described in children and adolescents with mesothelioma. These fusions occur most often in female patients with peritoneal primary mesotheliomas. ALK gene fusions involve various partner genes, including STRN, TPM1, and EML4.[1]

References:

1. Argani P, Lian DWQ, Agaimy A, et al.: Pediatric Mesothelioma With ALK Fusions: A Molecular and Pathologic Study of 5 Cases. Am J Surg Pathol 45 (5): 653-661, 2021.

Diagnostic Evaluation

Diagnostic thoracoscopy should be considered in suspicious cases to confirm diagnosis.[1] Cross-sectional imaging may suggest the diagnosis of peritoneal mesothelioma, but diagnostic biopsy by laparoscopy or open laparotomy is required.

References:

1. Nagata S, Nakanishi R: Malignant pleural mesothelioma with cavity formation in a 16-year-old boy. Chest 127 (2): 655-7, 2005.

Special Considerations for the Treatment of Children With Cancer

Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975.[1] Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:

• Primary care physicians.
• Pediatric surgeons.
• Radiation oncologists.
• Pediatric medical oncologists/hematologists.
• Rehabilitation specialists.
• Pediatric nurse specialists.
• Social workers.
• Child-life professionals.
• Psychologists.

For information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer.[2] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3,4,5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:

• A consensus effort between the European Union Joint Action on Rare Cancers and the European Cooperative Study Group for Rare Pediatric Cancers estimated that 11% of all cancers in patients younger than 20 years could be categorized as very rare. This consensus group defined very rare cancers as those with annual incidences of fewer than 2 cases per 1 million people. However, three additional histologies (thyroid carcinoma, melanoma, and testicular cancer) with incidences of more than 2 cases per 1 million people were also included in the very rare group because there is a lack of knowledge and expertise in the management of these tumors.[9]
• The Children's Oncology Group (COG) defines rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancers, melanomas and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinomas, nasopharyngeal carcinomas, and most adult-type carcinomas such as breast cancers, colorectal cancers, etc.).[10] These diagnoses account for about 5% of the cancers diagnosed in children aged 0 to 14 years and about 27% of the cancers diagnosed in adolescents aged 15 to 19 years.[4]

  Most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers in children aged 0 to 14 years and 9.3% of the cancers in adolescents aged 15 to 19 years.

These rare cancers are extremely challenging to study because of the low number of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer, such as Malignant Mesothelioma Treatment.

References:

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed December 15, 2023.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 15, 2023.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed August 18, 2023.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr.
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017.
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017.
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019.
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children's Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010.

Treatment of Childhood Mesothelioma

Treatment options for pediatric patients with malignant pleural mesotheliomas are controversial. Outcomes are often poor in these individuals despite treatment with radical surgical resection, chemotherapy, and radiation therapy. Treatments that use newer chemotherapy agents and immunotherapies are under investigation.[1]

Treatment options for childhood malignant mesothelioma include the following:

1. Surgery.
2. Chemotherapy.
3. Surgery and hyperthermic compartmental chemotherapy.
4. Radiation therapy.
5. Targeted therapy (ceritinib).

Surgery

Radical surgical resection has been attempted in patients with mesotheliomas with mixed results.[2] In adults, durable responses may be achieved with multimodal therapy that includes extrapleural pneumonectomy and radiation therapy after combination chemotherapy with pemetrexed-cisplatin.[3][Level of evidence B4] However, this approach remains highly controversial.[4]

Chemotherapy

The European Cooperative Study Group on Pediatric Rare Tumors retrospectively reviewed children, adolescents, and young adults (aged ≤21 years) with mesotheliomas who were treated between 1987 and 2018.[5] Investigators identified 15 male patients and 18 female patients with mesotheliomas. Only one patient had a documented asbestos exposure. In most patients, the primary tumor was located in the peritoneum (23 patients). Tumor histologies were either multicystic mesothelioma of the peritoneum (6 patients) or malignant mesothelioma (27 patients).

• The response rate to treatment with cisplatin-pemetrexed was 50% (6 of 12 cases).
• After a median follow-up period of 6.7 years (range, 0–20 years), the 5-year overall survival rate was 82.3%, and the event-free survival rate was 45.1%.
• All patients with multicystic mesothelioma remained alive after either surgery (5 patients) or cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (1 patient).

Surgery and Hyperthermic Compartmental Chemotherapy

Hyperthermic intrapleural/intraperitoneal chemotherapy (HIPEC) has been used to treat pleural and intraperitoneal mesotheliomas. HIPEC, in conjunction with radical surgical resection, has been used to treat adults with pleural mesotheliomas. Although results have been encouraging, HIPEC has not been validated in controlled clinical trials because pleural mesotheliomas are rare.[1,6,7] A single-institution study followed seven children with intraperitoneal mesotheliomas who were treated with surgery and HIPEC.[8] At last available follow-up, five of the seven patients were alive and had either minimal disease or no evaluable disease.

Radiation Therapy

Pain is an infrequent symptom in patients with mesotheliomas. However, if pain occurs, radiation therapy may be used for palliation.

Targeted Therapy (Ceritinib)

In one case report, a 13-year-old patient with a peritoneal mesothelioma and a STRN::ALK fusion responded to ceritinib treatment.[9]

For more information, see Malignant Mesothelioma Treatment.

References:

1. Carbone M, Adusumilli PS, Alexander HR, et al.: Mesothelioma: Scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin 69 (5): 402-429, 2019.
2. Maziak DE, Gagliardi A, Haynes AE, et al.: Surgical management of malignant pleural mesothelioma: a systematic review and evidence summary. Lung Cancer 48 (2): 157-69, 2005.
3. Krug LM, Pass HI, Rusch VW, et al.: Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clin Oncol 27 (18): 3007-13, 2009.
4. Treasure T: What is the best approach for surgery of malignant pleural mesothelioma? It is to put our efforts into obtaining trustworthy evidence for practice. J Thorac Cardiovasc Surg 151 (2): 307-9, 2016.
5. Orbach D, André N, Brecht IB, et al.: Mesothelioma in children and adolescents: the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) contribution. Eur J Cancer 140: 63-70, 2020.
6. Nguyen D, Sugarbaker DJ, Burt BM: Therapeutic R2 resection for pleural mesothelioma. J Thorac Cardiovasc Surg 155 (6): 2734-2735, 2018.
7. Wald O, Sugarbaker DJ: New Concepts in the Treatment of Malignant Pleural Mesothelioma. Annu Rev Med 69: 365-377, 2018.
8. Malekzadeh P, Good M, Hughes MS: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in pediatric patients with peritoneal mesothelioma: a single institution experience and long term follow up. Int J Hyperthermia 38 (1): 326-331, 2021.
9. Rüschoff JH, Gradhand E, Kahraman A, et al.: STRN -ALK Rearranged Malignant Peritoneal Mesothelioma With Dramatic Response Following Ceritinib Treatment. JCO Precis Oncol 3: , 2019.

Treatment Options Under Clinical Evaluation for Childhood Mesothelioma

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Latest Updates to This Summary (01 / 03 / 2024)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood mesothelioma. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Childhood Mesothelioma Treatment are:

• Denise Adams, MD (Children's Hospital Boston)
• Karen J. Marcus, MD, FACR (Dana-Farber Cancer Institute/Boston Children's Hospital)
• William H. Meyer, MD
• Paul A. Meyers, MD (Memorial Sloan-Kettering Cancer Center)
• Thomas A. Olson, MD (Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta - Egleston Campus)
• Alberto S. Pappo, MD (St. Jude Children's Research Hospital)
• Arthur Kim Ritchey, MD (Children's Hospital of Pittsburgh of UPMC)
• Carlos Rodriguez-Galindo, MD (St. Jude Children's Research Hospital)
• Stephen J. Shochat, MD (St. Jude Children's Research Hospital)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Mesothelioma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/mesothelioma/hp/child-mesothelioma-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 31593397]

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Last Revised: 2024-01-03