Wednesday, August 21, 2019

Childhood Salivary Gland Tumors Treatment (PDQ®)–Health Professional Version - National Cancer Institute

Childhood Salivary Gland Tumors Treatment (PDQ®)–Health Professional Version - National Cancer Institute



National Cancer Institute

Childhood Salivary Gland Tumors Treatment (PDQ®)–Health Professional Version

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Incidence and Outcome

Salivary gland tumors are rare and account for 0.5% of all malignancies in children and adolescents. After rhabdomyosarcoma, they are the most common tumor in the head and neck.[1,2] Salivary gland tumors may occur after radiation therapy and chemotherapy are given for treatment of primary leukemia or solid tumors.[3,4]
Overall 5-year survival in the pediatric age group is approximately 95%.[5] A review of the Surveillance, Epidemiology, and End Results database identified 284 patients younger than 20 years with tumors of the parotid gland.[6][Level of evidence: 3iA] Overall survival was 96% at 5 years, 95% at 10 years, and 83% at 20 years. Adolescents had higher mortality rates (7.1%) than did children younger than 15 years (1.6%; P = .23).
References
  1. Sultan I, Rodriguez-Galindo C, Al-Sharabati S, et al.: Salivary gland carcinomas in children and adolescents: a population-based study, with comparison to adult cases. Head Neck 33 (10): 1476-81, 2011. [PUBMED Abstract]
  2. Cesmebasi A, Gabriel A, Niku D, et al.: Pediatric head and neck tumors: an intra-demographic analysis using the SEER* database. Med Sci Monit 20: 2536-42, 2014. [PUBMED Abstract]
  3. Chowdhry AK, McHugh C, Fung C, et al.: Second primary head and neck cancer after Hodgkin lymphoma: a population-based study of 44,879 survivors of Hodgkin lymphoma. Cancer 121 (9): 1436-45, 2015. [PUBMED Abstract]
  4. Boukheris H, Stovall M, Gilbert ES, et al.: Risk of salivary gland cancer after childhood cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys 85 (3): 776-83, 2013. [PUBMED Abstract]
  5. Rutt AL, Hawkshaw MJ, Lurie D, et al.: Salivary gland cancer in patients younger than 30 years. Ear Nose Throat J 90 (4): 174-84, 2011. [PUBMED Abstract]
  6. Allan BJ, Tashiro J, Diaz S, et al.: Malignant tumors of the parotid gland in children: incidence and outcomes. J Craniofac Surg 24 (5): 1660-4, 2013. [PUBMED Abstract]

Clinical Presentation

Most salivary gland neoplasms arise in the parotid gland.[1-6] About 15% of these tumors arise in the submandibular glands or in the minor salivary glands under the tongue and jaw.[4] These tumors are most frequently benign but may be malignant, especially in young children.[7]
References
  1. da Cruz Perez DE, Pires FR, Alves FA, et al.: Salivary gland tumors in children and adolescents: a clinicopathologic and immunohistochemical study of fifty-three cases. Int J Pediatr Otorhinolaryngol 68 (7): 895-902, 2004. [PUBMED Abstract]
  2. Muenscher A, Diegel T, Jaehne M, et al.: Benign and malignant salivary gland diseases in children A retrospective study of 549 cases from the Salivary Gland Registry, Hamburg. Auris Nasus Larynx 36 (3): 326-31, 2009. [PUBMED Abstract]
  3. Fu H, Wang J, Wang L, et al.: Pleomorphic adenoma of the salivary glands in children and adolescents. J Pediatr Surg 47 (4): 715-9, 2012. [PUBMED Abstract]
  4. Galer C, Santillan AA, Chelius D, et al.: Minor salivary gland malignancies in the pediatric population. Head Neck 34 (11): 1648-51, 2012. [PUBMED Abstract]
  5. Thariat J, Vedrine PO, Temam S, et al.: The role of radiation therapy in pediatric mucoepidermoid carcinomas of the salivary glands. J Pediatr 162 (4): 839-43, 2013. [PUBMED Abstract]
  6. Chiaravalli S, Guzzo M, Bisogno G, et al.: Salivary gland carcinomas in children and adolescents: the Italian TREP project experience. Pediatr Blood Cancer 61 (11): 1961-8, 2014. [PUBMED Abstract]
  7. Laikui L, Hongwei L, Hongbing J, et al.: Epithelial salivary gland tumors of children and adolescents in west China population: a clinicopathologic study of 79 cases. J Oral Pathol Med 37 (4): 201-5, 2008. [PUBMED Abstract]

Histology and Molecular Features

The most common malignant salivary gland tumor in children is mucoepidermoid carcinoma, followed by acinic cell carcinoma and adenoid cystic carcinoma; less common malignancies include rhabdomyosarcoma, adenocarcinoma, and undifferentiated carcinoma.[1-6] Mucoepidermoid carcinoma is usually low or intermediate grade, although high-grade tumors do occur. Mammary analog secretory carcinoma (MASC) of the salivary gland is a newly described pathologic entity that has been seen in children. In one review, it was estimated that 12% of MASC cases occurred in the pediatric population.[7,8]
Immunohistochemical and molecular profiling in a series of pediatric patients with salivary gland tumors showed similarities to those tumors observed in adults.[9] In one study, 12 of 12 tumors were positive for MECT1-MAML2 fusion transcripts. This reflects the common chromosome translocation t(11;19)(q21;p13) that is seen in adults with salivary gland tumors.[10] MASC is characterized by an ETV6-NTRK3 fusion.[11]
Mucoepidermoid carcinoma is the most common type of treatment-related salivary gland tumor, and with standard therapy, the 5-year survival is about 95%.[5,12,13]
References
  1. Rahbar R, Grimmer JF, Vargas SO, et al.: Mucoepidermoid carcinoma of the parotid gland in children: A 10-year experience. Arch Otolaryngol Head Neck Surg 132 (4): 375-80, 2006. [PUBMED Abstract]
  2. Kupferman ME, de la Garza GO, Santillan AA, et al.: Outcomes of pediatric patients with malignancies of the major salivary glands. Ann Surg Oncol 17 (12): 3301-7, 2010. [PUBMED Abstract]
  3. Sultan I, Rodriguez-Galindo C, Al-Sharabati S, et al.: Salivary gland carcinomas in children and adolescents: a population-based study, with comparison to adult cases. Head Neck 33 (10): 1476-81, 2011. [PUBMED Abstract]
  4. Galer C, Santillan AA, Chelius D, et al.: Minor salivary gland malignancies in the pediatric population. Head Neck 34 (11): 1648-51, 2012. [PUBMED Abstract]
  5. Aro K, Leivo I, Mäkitie A: Management of salivary gland malignancies in the pediatric population. Curr Opin Otolaryngol Head Neck Surg 22 (2): 116-20, 2014. [PUBMED Abstract]
  6. Chiaravalli S, Guzzo M, Bisogno G, et al.: Salivary gland carcinomas in children and adolescents: the Italian TREP project experience. Pediatr Blood Cancer 61 (11): 1961-8, 2014. [PUBMED Abstract]
  7. Ngouajio AL, Drejet SM, Phillips DR, et al.: A systematic review including an additional pediatric case report: Pediatric cases of mammary analogue secretory carcinoma. Int J Pediatr Otorhinolaryngol 100: 187-193, 2017. [PUBMED Abstract]
  8. Khalele BA: Systematic review of mammary analog secretory carcinoma of salivary glands at 7 years after description. Head Neck 39 (6): 1243-1248, 2017. [PUBMED Abstract]
  9. Locati LD, Collini P, Imbimbo M, et al.: Immunohistochemical and molecular profile of salivary gland cancer in children. Pediatr Blood Cancer 64 (9): , 2017. [PUBMED Abstract]
  10. Techavichit P, Hicks MJ, López-Terrada DH, et al.: Mucoepidermoid Carcinoma in Children: A Single Institutional Experience. Pediatr Blood Cancer 63 (1): 27-31, 2016. [PUBMED Abstract]
  11. Skálová A, Vanecek T, Sima R, et al.: Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol 34 (5): 599-608, 2010. [PUBMED Abstract]
  12. Verma J, Teh BS, Paulino AC: Characteristics and outcome of radiation and chemotherapy-related mucoepidermoid carcinoma of the salivary glands. Pediatr Blood Cancer 57 (7): 1137-41, 2011. [PUBMED Abstract]
  13. Védrine PO, Coffinet L, Temam S, et al.: Mucoepidermoid carcinoma of salivary glands in the pediatric age group: 18 clinical cases, including 11 second malignant neoplasms. Head Neck 28 (9): 827-33, 2006. [PUBMED Abstract]

Treatment of Childhood Salivary Gland Tumors

Treatment options for childhood salivary gland tumors include the following:
  1. Surgery.
  2. Radiation therapy.
  3. Targeted therapy.
Radical surgical removal is the treatment of choice for salivary gland tumors whenever possible, with additional use of radiation therapy for high-grade tumors or tumors that have invasive characteristics such as lymph node metastasis, positive surgical margins, extracapsular extension, or perineural extension.[1-3]; [4][Level of evidence: 3iiiA] Parotid gland tumors are removed with the aid of neurological monitoring to prevent damage to the facial nerve.
One retrospective study compared proton therapy with conventional radiation therapy and found that proton therapy had a favorable acute toxicity and dosimetric profile.[5] Also, in a retrospective study, brachytherapy with iodine I 125 seeds was used to treat 24 children with mucoepidermoid carcinoma who had high-risk factors. Seeds were implanted within 4 weeks of surgical resection. With a median follow-up of 7.2 years, the disease-free and overall survival rates were 100%; no severe radiation-associated complications were reported.[6][Level of evidence: 3iiDi]
Objective responses have been observed in all reported patients with recurrent NTRKfusion–positive mammary analog secretory carcinomas who were treated with entrectinib or larotrectinib.[7,8] Ten of 11 adolescent or adult patients with TRK fusion–positive salivary gland tumors who were treated with larotrectinib experienced partial or complete responses.[8]
(Refer to the PDQ summary on Salivary Gland Cancer Treatment [Adult] for more information.)
References
  1. Rutt AL, Hawkshaw MJ, Lurie D, et al.: Salivary gland cancer in patients younger than 30 years. Ear Nose Throat J 90 (4): 174-84, 2011. [PUBMED Abstract]
  2. Ryan JT, El-Naggar AK, Huh W, et al.: Primacy of surgery in the management of mucoepidermoid carcinoma in children. Head Neck 33 (12): 1769-73, 2011. [PUBMED Abstract]
  3. Morse E, Fujiwara RJT, Husain Z, et al.: Pediatric Salivary Cancer: Epidemiology, Treatment Trends, and Association of Treatment Modality with Survival. Otolaryngol Head Neck Surg : 194599818771926, 2018. [PUBMED Abstract]
  4. Thariat J, Vedrine PO, Temam S, et al.: The role of radiation therapy in pediatric mucoepidermoid carcinomas of the salivary glands. J Pediatr 162 (4): 839-43, 2013. [PUBMED Abstract]
  5. Grant SR, Grosshans DR, Bilton SD, et al.: Proton versus conventional radiotherapy for pediatric salivary gland tumors: Acute toxicity and dosimetric characteristics. Radiother Oncol 116 (2): 309-15, 2015. [PUBMED Abstract]
  6. Mao MH, Zheng L, Wang XM, et al.: Surgery combined with postoperative (125) I seed brachytherapy for the treatment of mucoepidermoid carcinoma of the parotid gland in pediatric patients. Pediatr Blood Cancer 64 (1): 57-63, 2017. [PUBMED Abstract]
  7. Drilon A, Siena S, Ou SI, et al.: Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov 7 (4): 400-409, 2017. [PUBMED Abstract]
  8. Drilon A, Laetsch TW, Kummar S, et al.: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378 (8): 731-739, 2018. [PUBMED Abstract]

Treatment Options Under Clinical Evaluation for Childhood Salivary Gland Tumors

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.

Sialoblastoma

Sialoblastoma is a usually benign tumor presenting in the neonatal period, but has been reported to present as late as age 15 years. Sialoblastoma rarely metastasizes to the lungs, lymph nodes, or bones.[1]
Chemotherapy regimens with carboplatin, epirubicin, vincristine, etoposide, dactinomycin, doxorubicin, and ifosfamide have produced responses in two children with sialoblastoma.[2]; [3][Level of evidence: 3iiiDiv]
References
  1. Irace AL, Adil EA, Archer NM, et al.: Pediatric sialoblastoma: Evaluation and management. Int J Pediatr Otorhinolaryngol 87: 44-9, 2016. [PUBMED Abstract]
  2. Prigent M, Teissier N, Peuchmaur M, et al.: Sialoblastoma of salivary glands in children: chemotherapy should be discussed as an alternative to mutilating surgery. Int J Pediatr Otorhinolaryngol 74 (8): 942-5, 2010. [PUBMED Abstract]
  3. Scott JX, Krishnan S, Bourne AJ, et al.: Treatment of metastatic sialoblastoma with chemotherapy and surgery. Pediatr Blood Cancer 50 (1): 134-7, 2008. [PUBMED Abstract]

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:
  • 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.)
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 2002defines 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:
  • The Italian cooperative project on rare pediatric tumors (Tumori Rari in Eta Pediatrica [TREP]) 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 the remaining subgroup XI cancer 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 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.
Information about these tumors may also be found in sources relevant to adults with cancer such as the PDQ summary on Salivary Gland Cancer Treatment (Adult).
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. [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 June 04, 2019.

Changes to This Summary (08/16/2019)

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.
Treatment of Childhood Salivary Gland Tumors
Added targeted therapy as a treatment option for childhood salivary gland tumors.
Added text to state that ten of 11 adolescent or adult patients with TRK fusion–positive salivary gland tumors who were treated with larotrectinib experienced partial or complete responses.
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 salivary gland tumors. 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:
  • 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 Salivary Gland Tumors Treatment are:
  • Denise Adams, MD (Children's Hospital Boston)
  • Karen J. Marcus, MD (Dana-Farber Cancer Institute/Boston Children's Hospital)
  • 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)
  • R Beverly Raney, MD (Consultant)
  • 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.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”
The preferred citation for this PDQ summary is:
PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Salivary Gland Tumors Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/child/salivary-gland-treatment-pdq. Accessed <MM/DD/YYYY>.
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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