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 who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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).

Incidence, Risk Factors, and Clinical Presentation

Mesothelioma is extremely rare in childhood, 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] Mesothelioma may present in the thoracic/pleural region or in the peritoneum, and the two presentations have different clinical courses and prognoses.

Mesothelioma may develop after successful treatment of an earlier cancer, especially after treatment with radiation.[3,4] The amount of exposure required to develop cancer is unknown. In adults, these tumors have been associated with exposure to asbestos, which was used as building insulation.[5] There is no information about the risk for children exposed to asbestos.

This tumor can involve the membranous coverings of the lung, the heart, or the abdominal organs.[6-8]; [9][Level of evidence: 3iiA] These tumors can spread over the surface of organs, without invading far into the underlying tissue, and may spread to regional or distant lymph nodes.

Biologically, malignant mesothelioma occurring in children, adolescents, and young adults differs from its adult counterpart because there is no relationship to asbestos exposure. Recurrent genomic alterations have been described, including ALK fusions or fusions between the EWSR1 or FUS genes with either the ATF1 or YY1 genes.[10]

A multi-institutional collaboration performed an analysis of five children with intraperitoneal or paratesticular mesothelioma.[10] All five cases demonstrated fusions involving the ALK gene.

Prognosis

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

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.

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 for children and adolescents with cancer. 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.

(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)

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 2010, childhood cancer mortality decreased by more than 50%.[3] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[4] 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.[5,6] Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:

• The Italian Tumori Rari in Eta Pediatrica group defines a pediatric rare tumor as one with an incidence of less than two cases per 1 million population per year and is not included in other clinical trials.[7]
• The Children's Oncology Group has opted to define rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancer, melanoma and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinoma, nasopharyngeal carcinoma, and most adult-type carcinomas such as breast cancer, colorectal cancer, etc.).[8] These diagnoses account for about 4% of cancers diagnosed in children aged 0 to 14 years, compared with about 20% of cancers diagnosed in adolescents aged 15 to 19 years.[9]
  Most cancers within subgroup XI are either melanomas or thyroid cancer, with other types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of 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 the PDQ summary on Malignant Mesothelioma Treatment (Adult).

Treatment of Childhood Mesothelioma

Treatment options for childhood malignant mesothelioma include the following:

1. Surgery.
2. Chemotherapy.
3. Radiation therapy.

The treatment of patients with malignant pleural mesothelioma is controversial. Outcomes for patients are poor despite treatment with radical surgical resection, chemotherapy, and radiation therapy. Treatment with newer agents and immunotherapy is under investigation.[1]

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

Hyperthermic intrapleural chemotherapy, in conjunction with radical surgical resection, has been used to treat adults with pleural mesothelioma. Although results have been encouraging, hyperthermic intrapleural chemotherapy has not been validated in controlled clinical trials because of the rarity of the tumor.[1,5,6]

The European Cooperative Study Group on Pediatric Rare Tumors retrospectively reviewed children, adolescents, and young adults (aged ≤21 years) diagnosed with mesothelial tumors and treated between 1987 and 2018.[7] Investigators identified 15 male patients and 18 female patients. Only one patient had documented exposure to asbestos. The primary tumor was mainly in the peritoneum (23 patients). The histology was 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 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 were alive after surgery (5 patients) and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (1 patient).

Pain is an infrequent symptom. However, if it occurs, radiation therapy may be used for palliation.

Refer to the PDQ summary on Malignant Mesothelioma Treatment [Adult] for more information.

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, refer to the ClinicalTrials.gov website.

The following is an example of a national and/or institutional clinical trial that is currently being conducted:

• APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 4,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
  Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.

(Refer to the PDQ summary on Malignant Mesothelioma Treatment [Adult] for more information.)

Changes to This Summary (09/20/2021)

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.

Incidence, Risk Factors, and Clinical Presentation

Added text to state that mesothelioma may present in the thoracic/pleural region or in the peritoneum, and the two presentations have different clinical courses and prognoses.

Added text to state that biologically, malignant mesothelioma occurring in children, adolescents, and young adults differs from its adult counterpart because there is no relationship to asbestos exposure. Recurrent genomic alterations have been described, including ALK fusions or fusions between the EWSR1 or FUS genes with either the ATF1 or YY1 genes (cited Argani et al. as reference 10).

Added text to state that a multi-institutional collaboration performed an analysis of five children with intraperitoneal or paratesticular mesothelioma. All five cases demonstrated fusions involving the ALK gene.

Diagnostic Evaluation

Added text to state that cross-sectional imaging may suggest the diagnosis of peritoneal mesothelioma, but diagnostic biopsy by laparoscopy or open laparotomy is required.

Special Considerations for the Treatment of Children With Cancer

Added American Academy of Pediatrics as reference 2.

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® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary