Wednesday, August 21, 2019

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

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



National Cancer Institute

Childhood Laryngeal Tumors Treatment (PDQ®)–Health Professional Version

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Childhood Laryngeal Cancer

Histology

Tumors of the larynx are rare. The most common benign tumor is subglottic hemangioma.[1] Malignant tumors, which are especially rare, may be associated with benign tumors such as polyps and papillomas.[2,3]

Clinical Presentation

These tumors may present with the following:
  • Hoarseness.
  • Difficulty swallowing.
  • Enlargement of the lymph nodes of the neck.

Treatment of Childhood Laryngeal Cancer

Rhabdomyosarcoma is the most common pediatric malignant tumor of the larynx and is treated with chemotherapy and radiation therapy.[4] (Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.)
Squamous cell carcinoma of the larynx in children is managed in the same manner as it is in adults with carcinoma at this site, using surgery and radiation therapy.[5] Laser surgery may be the initial treatment used for these lesions. (Refer to the PDQ summary on Laryngeal Cancer Treatment [Adult] for more information about treatment of laryngeal cancer in adults.)

Treatment Options Under Clinical Evaluation for Childhood Laryngeal Cancer

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.
References
  1. Bitar MA, Moukarbel RV, Zalzal GH: Management of congenital subglottic hemangioma: trends and success over the past 17 years. Otolaryngol Head Neck Surg 132 (2): 226-31, 2005. [PUBMED Abstract]
  2. McGuirt WF Jr, Little JP: Laryngeal cancer in children and adolescents. Otolaryngol Clin North Am 30 (2): 207-14, 1997. [PUBMED Abstract]
  3. Bauman NM, Smith RJ: Recurrent respiratory papillomatosis. Pediatr Clin North Am 43 (6): 1385-401, 1996. [PUBMED Abstract]
  4. Pappo AS, Meza JL, Donaldson SS, et al.: Treatment of localized nonorbital, nonparameningeal head and neck rhabdomyosarcoma: lessons learned from intergroup rhabdomyosarcoma studies III and IV. J Clin Oncol 21 (4): 638-45, 2003. [PUBMED Abstract]
  5. Siddiqui F, Sarin R, Agarwal JP, et al.: Squamous carcinoma of the larynx and hypopharynx in children: a distinct clinical entity? Med Pediatr Oncol 40 (5): 322-4, 2003. [PUBMED Abstract]

Childhood Laryngeal Papillomatosis

General Information

Recurrent respiratory papillomatosis is the most common benign laryngeal tumor in children and is associated with human papillomavirus (HPV) infection, most commonly HPV-6 and HPV-11.[1,2] The presence of HPV-11 appears to correlate with a more aggressive clinical course than does the presence of HPV-6.[3] An Australian survey of pediatric otorhinolaryngologists documented a decline in the incidence of laryngeal papillomatosis after the introduction of HPV vaccinations for adolescent girls and young women aged 12 to 26 years.[4]
These tumors can cause hoarseness because of their association with wart-like nodules on the vocal cords, and they may rarely extend into the lung, producing significant morbidity.[5] Malignant degeneration may occur, with development of cancer in the larynx and squamous cell lung cancer.

Treatment of Childhood Laryngeal Papillomatosis

Papillomatosis is not cancerous, and primary treatment is surgical ablation with laser vaporization.[6] Frequent recurrences are common. Lung involvement, although rare, can occur.[5]
If a patient requires more than four surgical procedures per year, other interventions may be necessary, including the following:
  • Interferon therapy.[7]
  • Immunotherapy with HspE7, a recombinant fusion protein that has shown activity in other HPV-related diseases. A pilot study suggested a marked increase in the amount of time between surgeries.[8]
  • Laser therapy combined with intralesional bevacizumab.[9]
The effectiveness of intralesional cidofovir has not been conclusively demonstrated.[10]
The role of checkpoint inhibitors, such as PD-1 inhibitors, is currently being investigated.[11] Reports with small numbers of patients have documented that in selected cases, the administration of a quadrivalent HPV vaccine can be associated with a complete remission and an increase in the intersurgical interval.[12,13] In contrast, other reports have not documented a therapeutic effect of the quadrivalent HPV vaccine.[14]

Treatment Options Under Clinical Evaluation for Childhood Laryngeal Papillomatosis

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:
  • NCT02632344 (Pembrolizumab for HPV-associated Recurrent Respiratory Papilloma Patients With Laryngeal, Tracheal, and/or Pulmonary Involvement): In this research study, the investigators are determining whether pembrolizumab can restore the natural ability of the immune system to recognize and eliminate HPV-infected cells from the body. Pembrolizumab will be administered at a dose of 200 mg as a 30-minute intravenous infusion every 3 weeks. Treatment will be administered on day 1 of each cycle.
References
  1. Kashima HK, Mounts P, Shah K: Recurrent respiratory papillomatosis. Obstet Gynecol Clin North Am 23 (3): 699-706, 1996. [PUBMED Abstract]
  2. Derkay CS, Wiatrak B: Recurrent respiratory papillomatosis: a review. Laryngoscope 118 (7): 1236-47, 2008. [PUBMED Abstract]
  3. Maloney EM, Unger ER, Tucker RA, et al.: Longitudinal measures of human papillomavirus 6 and 11 viral loads and antibody response in children with recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 132 (7): 711-5, 2006. [PUBMED Abstract]
  4. Novakovic D, Cheng ATL, Zurynski Y, et al.: A Prospective Study of the Incidence of Juvenile-Onset Recurrent Respiratory Papillomatosis After Implementation of a National HPV Vaccination Program. J Infect Dis 217 (2): 208-212, 2018. [PUBMED Abstract]
  5. Gélinas JF, Manoukian J, Côté A: Lung involvement in juvenile onset recurrent respiratory papillomatosis: a systematic review of the literature. Int J Pediatr Otorhinolaryngol 72 (4): 433-52, 2008. [PUBMED Abstract]
  6. Andrus JG, Shapshay SM: Contemporary management of laryngeal papilloma in adults and children. Otolaryngol Clin North Am 39 (1): 135-58, 2006. [PUBMED Abstract]
  7. Avidano MA, Singleton GT: Adjuvant drug strategies in the treatment of recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg 112 (2): 197-202, 1995. [PUBMED Abstract]
  8. Derkay CS, Smith RJ, McClay J, et al.: HspE7 treatment of pediatric recurrent respiratory papillomatosis: final results of an open-label trial. Ann Otol Rhinol Laryngol 114 (9): 730-7, 2005. [PUBMED Abstract]
  9. Sidell DR, Nassar M, Cotton RT, et al.: High-dose sublesional bevacizumab (avastin) for pediatric recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol 123 (3): 214-21, 2014. [PUBMED Abstract]
  10. Chadha NK, James A: Adjuvant antiviral therapy for recurrent respiratory papillomatosis. Cochrane Database Syst Rev 12: CD005053, 2012. [PUBMED Abstract]
  11. Ivancic R, Iqbal H, deSilva B, et al.: Current and future management of recurrent respiratory papillomatosis. Laryngoscope Investig Otolaryngol 3 (1): 22-34, 2018. [PUBMED Abstract]
  12. Young DL, Moore MM, Halstead LA: The use of the quadrivalent human papillomavirus vaccine (gardasil) as adjuvant therapy in the treatment of recurrent respiratory papilloma. J Voice 29 (2): 223-9, 2015. [PUBMED Abstract]
  13. Mészner Z, Jankovics I, Nagy A, et al.: Recurrent laryngeal papillomatosis with oesophageal involvement in a 2 year old boy: successful treatment with the quadrivalent human papillomatosis vaccine. Int J Pediatr Otorhinolaryngol 79 (2): 262-6, 2015. [PUBMED Abstract]
  14. Katsuta T, Miyaji Y, Offit PA, et al.: Treatment With Quadrivalent Human Papillomavirus Vaccine for Juvenile-Onset Recurrent Respiratory Papillomatosis: Case Report and Review of the Literature. J Pediatric Infect Dis Soc 6 (4): 380-385, 2017. [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 Laryngeal 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.
Childhood Laryngeal Papillomatosis
Added text to state that an Australian survey of pediatric otorhinolaryngologists documented a decline in the incidence of laryngeal papillomatosis after the introduction of human papillomavirus vaccinations for adolescent girls and young women aged 12 to 26 years (cited Novakovic et al. as reference 4).
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 laryngeal cancer and papillomatosis. 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 Laryngeal 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 Laryngeal Tumors Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/child/laryngeal-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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