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医療専門家向け Childhood Pleuropulmonary Blastoma Treatment (PDQ®)

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This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood pleuropulmonary blastoma. 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).

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Types of Pleuropulmonary Blastoma

Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy that can present as a pulmonary or pleural mass. In most cases, pleuropulmonary blastoma is associated with germline mutations of the DICER1 gene. The International Pleuropulmonary Blastoma Registry is a valuable resource for information on this rare malignancy.[ 1 ][ 2 ]

The following three subtypes of pleuropulmonary blastoma have been identified:

The Pleuropulmonary Blastoma Registry reported on 350 centrally reviewed and confirmed cases of pleuropulmonary blastoma over a 50-year period (refer to Table 1).[ 2 ]

Table 1. Relative Proportions and Features of Pleuropulmonary Blastomaa
Type I Type Ir Type II Type II/III or III
aAdapted from Messinger et al.[ 2 ]
Relative proportion of pleuropulmonary blastoma cases 33% 35% 32%
Presence of germline DICER1 mutation 62% 63% 75%
Median age at diagnosis (months) 8 47 35 41
5-year overall survival 89% 100% 71% 53%
参考文献
  1. The International Pleuropulmonary Blastoma/DICER1 Registry. Minneapolis, Minn: Children's Hospitals and Clinics of Minnesota. Available online. Last accessed January 31, 2020.[PUBMED Abstract]
  2. Messinger YH, Stewart DR, Priest JR, et al.: Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer 121 (2): 276-85, 2015.[PUBMED Abstract]
  3. Hill DA, Jarzembowski JA, Priest JR, et al.: Type I pleuropulmonary blastoma: pathology and biology study of 51 cases from the international pleuropulmonary blastoma registry. Am J Surg Pathol 32 (2): 282-95, 2008.[PUBMED Abstract]
  4. Priest JR, McDermott MB, Bhatia S, et al.: Pleuropulmonary blastoma: a clinicopathologic study of 50 cases. Cancer 80 (1): 147-61, 1997.[PUBMED Abstract]
  5. Dehner LP, Messinger YH, Schultz KA, et al.: Pleuropulmonary Blastoma: Evolution of an Entity as an Entry into a Familial Tumor Predisposition Syndrome. Pediatr Dev Pathol 18 (6): 504-11, 2015 Nov-Dec.[PUBMED Abstract]
  6. Priest JR, Hill DA, Williams GM, et al.: Type I pleuropulmonary blastoma: a report from the International Pleuropulmonary Blastoma Registry. J Clin Oncol 24 (27): 4492-8, 2006.[PUBMED Abstract]
  7. Miniati DN, Chintagumpala M, Langston C, et al.: Prenatal presentation and outcome of children with pleuropulmonary blastoma. J Pediatr Surg 41 (1): 66-71, 2006.[PUBMED Abstract]
Molecular Features

In one report, 15 of 16 pleuropulmonary blastoma tumors were positive for IGF1R expression by immunohistochemistry.[ 1 ] Genomic profiling showed amplification of the IGF1R gene in 4 of 16 pleuropulmonary blastoma tumors; all of these gene-amplified tumors were Type III.

参考文献
  1. Vokuhl C, de Leon-Escapini L, Leuschner I: Strong Expression and Amplification of IGF1R in Pleuropulmonary Blastomas. Pediatr Dev Pathol 20 (6): 475-481, 2017 Nov-Dec.[PUBMED Abstract]
Prognostic Factors

In a comprehensive analysis of 350 patients reported by the Pleuropulmonary Blastoma Registry, only two prognostic factors were identified: the type of pleuropulmonary blastoma and the presence of metastatic disease at diagnosis.[ 1 ] (Refer to Table 1.) In three additional small cohort series, the ability to perform a complete surgical resection was also identified as a prognostic factor.[ 2 ][ 3 ][ 4 ]

The presence of a germline DICER1 mutation is not a prognostic factor.[ 1 ]

参考文献
  1. Messinger YH, Stewart DR, Priest JR, et al.: Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer 121 (2): 276-85, 2015.[PUBMED Abstract]
  2. Indolfi P, Bisogno G, Casale F, et al.: Prognostic factors in pleuro-pulmonary blastoma. Pediatr Blood Cancer 48 (3): 318-23, 2007.[PUBMED Abstract]
  3. Bisogno G, Brennan B, Orbach D, et al.: Treatment and prognostic factors in pleuropulmonary blastoma: an EXPeRT report. Eur J Cancer 50 (1): 178-84, 2014.[PUBMED Abstract]
  4. Sparber-Sauer M, Seitz G, Kirsch S, et al.: The impact of local control in the treatment of type II/III pleuropulmonary blastoma. Experience of the Cooperative Weichteilsarkom Studiengruppe (CWS). J Surg Oncol 115 (2): 164-172, 2017.[PUBMED Abstract]
Risk Factors

Close to two-thirds of patients with pleuropulmonary blastoma have a germline DICER1 mutation. Approximately one-third of families of children with pleuropulmonary blastoma manifest a number of dysplastic and/or neoplastic conditions comprising the DICER1 syndrome.[ 1 ][ 2 ][ 3 ] Most mutation carriers are unaffected, indicating that tumor risk is modest.[ 2 ]

Germline DICER1 mutations have been associated with the following:[ 1 ][ 2 ][ 3 ][ 4 ][ 5 ]

The penetrance of DICER1 mutations associated with each pathologic condition is not well understood, but lung cysts, pleuropulmonary blastoma, and thyroid nodules are the most commonly reported manifestations in individuals who have loss-of-function mutations.[ 5 ] Most associated conditions occur in children younger than 10 years, although ovarian tumors and multinodular goiters are described in children and adults aged up to 30 years.[ 3 ][ 5 ] Surveillance and screening recommendations have been proposed.[ 5 ]

参考文献
  1. Hill DA, Ivanovich J, Priest JR, et al.: DICER1 mutations in familial pleuropulmonary blastoma. Science 325 (5943): 965, 2009.[PUBMED Abstract]
  2. Slade I, Bacchelli C, Davies H, et al.: DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet 48 (4): 273-8, 2011.[PUBMED Abstract]
  3. Foulkes WD, Bahubeshi A, Hamel N, et al.: Extending the phenotypes associated with DICER1 mutations. Hum Mutat 32 (12): 1381-4, 2011.[PUBMED Abstract]
  4. Schultz KA, Pacheco MC, Yang J, et al.: Ovarian sex cord-stromal tumors, pleuropulmonary blastoma and DICER1 mutations: a report from the International Pleuropulmonary Blastoma Registry. Gynecol Oncol 122 (2): 246-50, 2011.[PUBMED Abstract]
  5. Schultz KAP, Williams GM, Kamihara J, et al.: DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies. Clin Cancer Res 24 (10): 2251-2261, 2018.[PUBMED Abstract]
  6. Boman F, Hill DA, Williams GM, et al.: Familial association of pleuropulmonary blastoma with cystic nephroma and other renal tumors: a report from the International Pleuropulmonary Blastoma Registry. J Pediatr 149 (6): 850-854, 2006.[PUBMED Abstract]
Surveillance

As with other cancer predisposition conditions, before individuals with DICER1 mutations are screened, factors that must be considered include typical age of onset of each disease, potential benefits of early detection, and risks and availability of screening modalities. A consensus panel convened by the International Pleuropulmonary Blastoma Registry has proposed guidelines for surveillance. In addition to imaging-based surveillance, individuals and families can be counseled at each visit regarding potential signs and symptoms of DICER1-associated conditions and undergo appropriate age-specific and gender-specific preventive screening studies (refer to Figure 1).[ 1 ]

Table showing the suggested signs and symptoms and imaging surveillance by system for individuals with DICER1 pathogenic variants.

画像を拡大する

Figure 1. Suggested signs and symptoms and imaging surveillance by system for individuals with DICER1 pathogenic variants. Adapted from Clinical Cancer Research, Copyright 2018, Volume 20/Issue 10, Pages 2251–2261, Kris Ann P. Schultz, Gretchen M. Williams, Junne Kamihara, et al.: DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies, with permission from AACR.

参考文献
  1. Schultz KAP, Williams GM, Kamihara J, et al.: DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies. Clin Cancer Res 24 (10): 2251-2261, 2018.[PUBMED Abstract]
Clinical Presentation

Presenting symptoms are not specific, and commonly include the following:

The tumor is usually located in the lung periphery, but it may be extrapulmonary with involvement of the heart/great vessels, mediastinum, diaphragm, and/or pleura.[ 1 ][ 2 ] Tumor embolism is a known risk, and radiographic evaluation of the central circulation is performed to identify potentially fatal embolic complications.[ 3 ]

参考文献
  1. Indolfi P, Bisogno G, Casale F, et al.: Prognostic factors in pleuro-pulmonary blastoma. Pediatr Blood Cancer 48 (3): 318-23, 2007.[PUBMED Abstract]
  2. Bisogno G, Brennan B, Orbach D, et al.: Treatment and prognostic factors in pleuropulmonary blastoma: an EXPeRT report. Eur J Cancer 50 (1): 178-84, 2014.[PUBMED Abstract]
  3. Priest JR, Andic D, Arbuckle S, et al.: Great vessel/cardiac extension and tumor embolism in pleuropulmonary blastoma: a report from the International Pleuropulmonary Blastoma Registry. Pediatr Blood Cancer 56 (4): 604-9, 2011.[PUBMED Abstract]
Treatment of Childhood Pleuropulmonary Blastoma

There are no standard treatment options. Current treatment regimens for these rare tumors have been informed by consensus opinion.

Treatment options for childhood pleuropulmonary blastoma include the following:

  1. Surgery.
  2. Adjuvant chemotherapy.

A complete surgical resection is required for cure.[ 1 ]

Data from the International Pleuropulmonary Blastoma Registry and the European Cooperative Study Group in Pediatric Rare Tumors (EXPeRT) suggest that adjuvant chemotherapy may reduce the risk of recurrence.[ 2 ]; [ 3 ][Level of evidence: 3iiiA] Responses to chemotherapy have been reported with agents similar to those used for the treatment of rhabdomyosarcoma.[ 2 ][ 3 ][ 4 ]

Some general treatment considerations from the International Pleuropulmonary Blastoma Registry include the following:[ 2 ][ 5 ]

  1. Type I and Type Ir: Surgery is the treatment of choice for Type I and Type Ir pleuropulmonary blastoma. In the Pleuropulmonary Blastoma Registry series, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 82% and 91%, respectively. Approximately 10% of the cases may progress to Type II or Type III after surgery, but adjuvant chemotherapy does not appear to have an impact on the rate of progression and survival.[ 2 ][ 3 ]
  2. Type II and Type III: A multimodal sarcoma treatment approach is recommended for Type II and Type III pleuropulmonary blastoma, usually including rhabdomyosarcoma regimens and either upfront or delayed surgery.[ 2 ][ 3 ][ 6 ] Anthracycline-containing regimens appear to be superior.[ 3 ] The respective 5-year DFS and OS rates were 59% and 71% for Type II and 37% and 53% for Type III.[ 2 ] The role of radiation therapy is not well defined. While the use of radiation did not impact survival in the International Pleuropulmonary Blastoma Registry series, only 20% of patients with Type II and Type III received it.[ 2 ] Approximately 50% of relapses occur in the brain.[ 2 ]
参考文献
  1. Indolfi P, Bisogno G, Casale F, et al.: Prognostic factors in pleuro-pulmonary blastoma. Pediatr Blood Cancer 48 (3): 318-23, 2007.[PUBMED Abstract]
  2. Messinger YH, Stewart DR, Priest JR, et al.: Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer 121 (2): 276-85, 2015.[PUBMED Abstract]
  3. Bisogno G, Brennan B, Orbach D, et al.: Treatment and prognostic factors in pleuropulmonary blastoma: an EXPeRT report. Eur J Cancer 50 (1): 178-84, 2014.[PUBMED Abstract]
  4. Venkatramani R, Malogolowkin MH, Wang L, et al.: Pleuropulmonary blastoma: a single-institution experience. J Pediatr Hematol Oncol 34 (5): e182-5, 2012.[PUBMED Abstract]
  5. The International Pleuropulmonary Blastoma/DICER1 Registry. Minneapolis, Minn: Children's Hospitals and Clinics of Minnesota. Available online. Last accessed January 31, 2020.[PUBMED Abstract]
  6. Sparber-Sauer M, Seitz G, Kirsch S, et al.: The impact of local control in the treatment of type II/III pleuropulmonary blastoma. Experience of the Cooperative Weichteilsarkom Studiengruppe (CWS). J Surg Oncol 115 (2): 164-172, 2017.[PUBMED Abstract]
Treatment Options Under Clinical Evaluation for Childhood Pleuropulmonary Blastoma

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:

Special Considerations for the Treatment of Children With Cancer

Cancer in children and adolescents is rare, although the overall incidence of childhood cancer 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:

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

Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[ 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 in these trials 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 therapy that is currently accepted as standard. 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 cancer therapy side effects 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 persons. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. Adult rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people, and they are estimated to 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:

These rare cancers are extremely challenging to study because of the low incidence 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.

参考文献
  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.[PUBMED Abstract]
  2. Corrigan JJ, Feig SA; American Academy of Pediatrics: Guidelines for pediatric cancer centers. Pediatrics 113 (6): 1833-5, 2004.[PUBMED Abstract]
  3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.[PUBMED Abstract]
  4. 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.[PUBMED Abstract]
  5. 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.[PUBMED Abstract]
  6. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017.[PUBMED Abstract]
  7. Ferrari A, Bisogno G, De Salvo GL, et al.: The challenge of very rare tumours in childhood: the Italian TREP project. Eur J Cancer 43 (4): 654-9, 2007.[PUBMED Abstract]
  8. 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.[PUBMED Abstract]
  9. Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2012. Bethesda, Md: National Cancer Institute, 2015. Also available online. Last accessed February 20, 2020.[PUBMED Abstract]
Changes to This Summary (01/31/2020)

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.

Molecular Features

Added this new section.

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

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood pleuropulmonary blastoma. 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.

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:

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.

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PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Pleuropulmonary Blastoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/lung/hp/child-pleuropulmonary-blastoma-treatment-pdq. Accessed <MM/DD/YYYY>.

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