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Pediatric head and neck squamous cell carcinoma: Patient demographics, treatment trends and outcomes
International Journal of Pediatric Otorhinolaryngology 106 (2018) 21–25
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Pediatric head and neck squamous cell carcinoma: Patient demographics, treatment trends and outcomes
T
Ankit Modha, Omar H. Gayarb, Mohamed A. Elshaikha, Arnold C. Paulinoc, Farzan Siddiquia,∗ a
Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI, USA Department of Radiation Oncology, Karmanos Cancer Institute - McLaren Flint, Flint, MI, USA c Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA b
A R T I C L E I N F O
A B S T R A C T
Keywords: Pediatric cancer Head and neck cancer Treatment outcomes Trends NCDB
Objectives: To examine patient demographics, temporal and treatment trends, and survival outcomes of pediatric non-nasopharyngeal head and neck squamous cell carcinomas using the National Cancer Database. Methods: The National Cancer Database was queried for pediatric patients (age 0–19 years) diagnosed with squamous cell carcinoma of the head and neck (including oral cavity, oropharynx, nasal cavity, larynx, hypopharynx, and salivary glands) from 2004 to 2013. Results: Of 159 patients identified, the majority had oral cavity SCC (55%). There was no discernable change in incidence trends over the study period with the number of cases per year ranging from 10 to 20 (R2 = 0.174). The predominant treatment regimen for the nasal cavity was trimodality (surgery, radiation, and chemotherapy) treatment (29%), chemotherapy and radiation for the oropharynx (40%), and surgery alone for salivary gland (47%), oral cavity (44%), and larynx (22%). The 5-year overall survival for the entire cohort was 74% and by subsite: oral cavity (66%), oropharynx (68%), nasal cavity (75%), and larynx (95%). Laryngeal disease had statistically significant longer survival when compared to oral cavity (p = .031) or oropharynx (p = .029). Conclusion: Although pediatric non-nasopharyngeal head and neck squamous cell carcinomas are rare, practitioners should be aware of this entity and consider it in the differential diagnosis of pediatric malignancies.
1. Introduction
2. Methods
Head and neck squamous cell carcinomas (SCC) are common in adults but considered very rare in the pediatric population. However, there is evidence of rising incidence of pediatric head and neck cancer [1], which is concerning considering little is known about the characteristics of this malignancy in this population. While nasopharyngeal carcinoma appears to have a bimodal distribution of cases ranging from the young to the elderly [2], non-nasopharyngeal SCC is very uncommon with most studies limited to case reports or small series [3,4]. There is limited information regarding appropriate management and care of these patients and most approaches are extrapolated from adult head and neck SCC [5]. Because paucity of information is available for this rare entity, we used the National Cancer Database (NCDB) to examine temporal and treatment trends as well as survival outcomes of pediatric non-nasopharyngeal HNSCC.
This retrospective study utilized the NCDB, which is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The clinical oncology outcomes database is sourced from hospital registry data collected in more than 1500 Commission on Cancer accredited facilities presenting nearly 70% of all new invasive cancer diagnoses in the US each year [6]. The use of this database is exempt from institutional review board authorization. The NCDB was queried for pediatric (age 0–19 years) patients diagnosed with SCC of the head and neck of all stages (including oral cavity, oropharynx, nasal cavity, larynx, hypopharynx, and salivary glands). Patients with incomplete or missing follow-up were excluded. Only histology codes for carcinoma, not otherwise specified; carcinoma, undifferentiated, not otherwise specified; SCC, not otherwise specified; and lymphoepithelial carcinoma (8010, 8020, 8070-8071, and 80828083) were included. Patient demographics and treatment characteristics were evaluated. Linear regression was used to evaluate the trends in the number of cases by year of diagnosis. Kaplan-Meir plots for overall survival were
∗
Corresponding author. Department of Radiation Oncology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. E-mail address: [email protected] (F. Siddiqui).
https://doi.org/10.1016/j.ijporl.2017.12.032 Received 30 October 2017; Received in revised form 26 December 2017; Accepted 29 December 2017 Available online 03 January 2018 0165-5876/ © 2018 Published by Elsevier B.V.
International Journal of Pediatric Otorhinolaryngology 106 (2018) 21–25
A. Modh et al.
Table 1 (continued)
Table 1 Patient characteristics of the study cohort of 159 patients with pediatric head and neck cancer. Characteristic
Characteristic 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
No. of Patients (%)
Age at diagnosis, years Median (range) 0-4 5-10 11-15 16-19
17 (0–19) 9 (6%) 14 (9%) 35 (22%) 101 (63%)
No. of Patients (%) 20 14 19 10 15 14 16 13 17 11
(13%) (9%) (12%) (13%) (9%) (9%) (10%) (8%) (11%) (7%)
Sex Male Female
FOM, floor of mouth; NCDB, National Cancer Database; NOS, not otherwise specified; SCC, squamous cell carcinoma.
96 (61%) 63 (39%)
generated and log-rank tests were used to evaluate outcomes across the cohort and stratified by subsite.
Race White Black Other
128 (81%) 17 (11%) 14 (8%)
3. Results
Site Lip FOM Gum Palate Tongue Larynx Hypopharynx Parotid gland Other salivary gland Tonsil Oropharynx Pharynx Nasal cavity Other (oral cavity, NOS)
We identified a total of 159 patients from 2004 to 2013. There was a male predominance (61%) with the median age of 17 years (range 0–19). Sixty-three percent of the patients were adolescents aged 16–19 years. Table 1 details the patient demographics. The majority of patients had disease in the oral cavity (55%). Additionally, 14% had a laryngeal primary, 13% in the nasal cavity, 11% in the salivary gland, and 6% with oropharyngeal tumors as well as 1 case in the hypopharynx. The most common stage grouping was stage IV (33%). There was a steady number of cases per year, ranging from 10 to 20 per year, without any discernable increase or decrease (R2 = 0.174). The 5-year overall survival for the entire cohort was 74% (Fig. 1) and by subsite (Fig. 2): oral cavity (66%), oropharynx (68%), nasal cavity (75%), and larynx (95%). Laryngeal disease had statistically significant longer survival when compared to oral cavity (p = .031) or oropharynx (p = .029). Table 2 details the treatment characteristics by head and neck subsite. The predominant treatment regimen for the oral cavity was surgery alone (44%). The nasal cavity was treated equally (29%) with chemotherapy and radiation as well as trimodality treatment. Laryngeal cancers were treated equally (22%) with surgery alone or chemotherapy and radiation. The one case of hypopharyngeal cancer was treated with radiation alone. Forty percent of oropharyngeal cancers were treated with chemotherapy and radiation and 47% of salivary gland cancers were treated with surgery alone.
8 (5%) 3 (2%) 10 (6%) 6 (4%) 57 (36%) 22 (14%) 1 (< 1%) 10 (6%) 7 (4%) 6 (4%) 2 (1%) 2 (1%) 21 (13%) 4 (3%)
Site (sorted) Oral cavity Oropharynx Nasal cavity Larynx Hypopharynx Salivary gland
88 (55%) 10 (6%) 21 (13%) 22 (14%) 1 (< 1%) 17 (11%)
Histology Carcinoma, NOS Papillary SCC SCC, NOS SCC, keratinizing SCC, non- keratinizing Lymphoepithelial carcinoma Basaloid SCC
16 (10%) 5 (3%) 93 (59%) 24 (15%) 7 (4%) 4 (3%) 10 (6%)
NCDB Analytic Stage Group 1 2 3 4 Unknown
48 17 18 52 24
(30%) (11%) (11%) (33%) (15%)
33 53 31 14 28
(21%) (33%) (19%) (9%) (18%)
Grade Well differentiated Moderately differentiated Poorly differentiated Undifferentiated Unknown Year of diagnosis Fig. 1. Kaplan-Meir plot for overall survival for the entire study cohort.
22
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and 1 larynx. The 1 patient with low-risk HPV had cancer of the pharynx. 4. Discussion We present one of the largest series of pediatric head and neck nonnasopharyngeal SCC. Reassuringly, the annual number of cases identified remained steady across the study period. In their analysis of Surveillance, Epidemiology, and End Results data, Albright et al. identified 3050 pediatric head and neck tumors from 1973 to 1996, with histologies ranging from lymphomas, sarcomas, and adenocarcinomas, amongst many others. They found an increased incidence of head and neck malignancies in patients younger than 15 years old when comparing the incidence of pediatric cancers as a whole over that time period. Pediatric cases of SCC in that series, however, accounted for less than 2% (54) of patients [7]. While the data presented here is from a different national database, there were more cases identified in our series over a shorter time period. There are no universally accepted treatment guidelines due to the rarity of pediatric head and neck cancers. The treatment patterns of these malignancies in our series mirror those of their adult subsite counterparts. While there is limited information in our cohort to make inferences of treatment on survival, in their systematic review with individual patient data of 217 cases of pediatric HNSCC, Bhanu Prasad et al. revealed a favorable survival for patients treated with surgery alone or surgery followed by adjuvant radiation. The patterns of care delivered in their study also reflected those of adult patients with HNSCC [8]. Six patients, however, did not receive any treatment in our series. This may reflect a limitation of the database rather than actual nontreatment. The cohorts are hospital-based and not population-based.
Fig. 2. Kaplan-Meir plot for overall survival stratified by head and neck subsite. The one case of hypopharyngeal cancer was included with the laryngeal cohort.
Additional pathologic and tumor characteristics of the study cohort are presented in Table 3. When surgery was performed, the majority of patients had negative margins and no residual tumor present (52%). Of these, the most common pathologic TMN stage group was I (20%). Of 19 patients who had Human Papilloma Virus (HPV) testing, 6 patients were positive for high risk subtypes (16 or 18) and 1 patient was positive with low-risk subtypes. These patients represent 4% (7 of 159) of the entire cohort or 37% (7 of 19) of those tested. Of the high risk subtypes, 3 were cancers of the oral cavity, 1 pharynx, 1 nasal cavity,
Table 2 Treatment characteristics. Surgery
None Biopsy/local excision Radical excisiona Surgery, NOS
Oral Cavity (n = 88)
Oropharynx (n = 10)
Nasal Cavity (n = 21)
Larynx/Hypopharynxb (n = 23)
Salivary Gland (n = 17)
N (%)
N (%)
N (%)
N (%)
N (%)
15 (17%) 8 (9%) 62 (71%) 3 (3%)
6 (60%) 2 (20%) 2 (20%) 0
9 (43%) 5 (24%) 7 (33%) 0
12 (52%) 8 (35%) 1 (4%) 2 (9%)
2 (12%) 5 (29%) 10 (59%) 0
41 (47%) 42 (48%) 1 (1%) 1 (1%) 3 (3%)
2 (20%) 7 (70%) 0 0 1 (10%)
7 (33%) 13 (62%) 0 1 (5%) 0
9 (39%) 13 (57%) 0 1 (4%) 0
8 (47%) 9 (24%) 0 0 0
55 (63%) 30 (34%) 3 (3%)
1 (10%) 8 (80%) 1 (10%)
8 (38%) 13 (63%) 0
14 (61%) 9 (39%) 0
13 (76%) 4 (24%) 0
1 0 0 0 0 1 4 3 1
2 4 0 1 2 0 6 6 0
2 5 4 1 3 1 5 2 0
0 8 0 0 5 0 2 2 0
Radiation None EBRT Brachytherapy Radiation, NOS Unknown Chemotherapy None Administered Unknown
Combined modality treatment No therapy Surgery alone RT alone CT alone S + RT S + CT CT + RT S + RT + CT Unknown
1 (1%) 39 (44%) 0 1 (1%) 14 (16%) 0 13 (15%) 16 (18%) 4 (4%)
(10%)
(10%) (40%) (30%) (10%)
(9%) (19%) (5%) (9%) (29%) (29%)
CT, chemotherapy; EBRT, external beam radiation therapy; NOS, not otherwise specified; RT, radiation; S, surgery. a Includes glossectomy, pharyngectomy, laryngectomy, or parotidectomy when specified. b The one case of hypopharyngeal cancer was treated with radiation alone.
23
(9%) (22%) (17%) (4%) (13%) (4%) (22%) (9%)
(47%)
(29%) (12%) (12%)
International Journal of Pediatric Otorhinolaryngology 106 (2018) 21–25
A. Modh et al.
elsewhere. An advantage of the NCDB over other registry data is that it captures approximately 70% of all incident cancers in the US and includes more complete information on treatment, such as radiation dose/target and chemotherapy data [6]. There are 111 pediatric hospitals that contribute data to the NCDB, including St. Jude Children's Research Hospital, Texas and Boston Children's Hospitals. The patients in our study had a favorable long-term survival when compared to survival for adult head and neck SCC [10]. Bhanuprasad et al. presented their experience treating 12 cases of head and neck SCC, most of which were also of the oral cavity. Of the evaluable patients, all patients were surviving at last follow-up without disease (with a median follow-up of 2 years) [5]. An aged-matched group of 10 pediatric patients with oral tongue SCC treated at Memorial Sloan-Kettering Cancer Center reported an equivalent 5-year overall survival (70% in the pediatric group and 64% in the adult group) [11]. The laryngeal patients in our cohort also had very good overall survival. Over 50% of the laryngeal patients in our cohort had early stage disease, which may explain this favorable outcome. Siddiqui et al. reported 6 patients with SCC of the larynx and hypopharynx. Of these, 3 patients with laryngeal primaries had their disease controlled at last follow-up [4]. Additionally, there may be different etiologic origins of the disease in the larynx of pediatric patients. Two of the 3 larynx patients in another case series were HPV-16 positive [3], which is uncommon in the adult laryngeal cancer population, the majority of which is smoking and alcohol related. There were 7 patients in our cohort which were HPV positive, although only a limited number had HPV testing. Of these only 2 patients had oropharyngeal cancer, where this virus is typically correlated with in the adult population. Additionally, a recent case report discussed a case of spontaneous regression of a 10-year old patient with laryngeal carcinoma which was HPV-26 positive, which is not typically oncogenic [12]. This analysis of a large hospital-based registry has a number of limitations, including inherent biases of retrospective analyses. Registry data have been shown to report variable rates of actual treatment delivered [13]. Additionally, the NCDB lacks data on recurrence patterns, treatment toxicity, and etiologic factors such as smoking, all of which are very relevant for this patient population.
Table 3 Additional pathologic and tumor characteristics of the study cohort. Characteristic
No. of Patients (%)
AJCC (TMN) Clinical Stage I II III IV, NOS IVA IVB IVC Unknown
39 (24%) 25 (16%) 12 (8%) 2 (1%) 36 (23%) 4 (2%) 1 (1%) 40 (25%)
AJCC (TMN) Pathological Stage I II III IV, NOS IVA IVB IVC Unknown
32 (20%) 11 (7%) 11 (7%) 1 (1%) 23 (14%) 1 (1%) 1 (1%) 79 (49%)
Tumor Size Microscopic only 4-20 mm 21-40 mm 41-60 mm 61-80 mm 81-100 mm 150 mm 480-500 mm Described as less than Described as less than Described as less than Described as less than Described as less than Unknown
1 cm 2 cm 3 cm 4 cm 5 cm
2 (1%) 42 (26%) 41 (25%) 10 (6%) 4 (2%) 3 (2%) 1 (1%) 2 (1%) 1 (1%) 2 (1%) 0 (0%) 1 (1%) 2 (1%) 48 (29%)
Surgical Margins No residual tumor Residual tumor, NOS Microscopic residual Macroscopic residual Not evaluable No surgery Unknown
83 (52%) 4 (2%) 7 (4%) 1 (1%) 6 (4%) 44 (28%) 14 (9%)
5. Conclusion In conclusion, the number of cases of pediatric non-nasopharyngeal head and neck SCC remained steady over the study period. Although rare, practitioners should be aware of this entity and consider it in the differential diagnosis of pediatric malignancies.
Pathologic Nodal ECE
Funding No nodal involvement Nodal involvement, no ECE ECE present Nodes not collected, FNA, or information not collected Unknown
16 (10%) 7 (4%) 4 (3%) 121 (76%) 11 (7%)
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflicts of interest
HPV Status Negative Positive for low-risk types Positive for high-risk types Not collected or not done Unknown
The authors declare no conflicts of interest.
12 (7%) 1 (1%) 6 (4%) 114 (72%) 26 (16%)
Presentations Accepted for presentation at the 2018 Multidisciplinary Head and Neck Cancers Symposium, Scottsdale, Arizona, February 2018.
AJCC, American Joint Committee on Cancer; ECE, extracapsular extension; HPV, Human Papilloma Virus; NOS, not otherwise specified; TMN tumor, node and metastasis.
References They are identified from the hospitals where they present for diagnosis and/or treatment, and the potential exists for patients to be diagnosed at a participating hospital but treated at a facility not participating or contributing to the NCDB [9]. Four of the 6 patients had their initial diagnosis at the reporting facility and part or all of their treatment
[1] C.F.E. Kirsch, G. Dellacerra, Increasing incidence and imaging in pediatric head and neck cancer and role of the human papilloma virus and Epstein–Barr virus, J. Pediatr. Neuroradiol. 5 (3) (2016) 221–228. [2] F. Bray, M. Haugen, T.A. Moger, et al., Age-incidence curves of nasopharyngeal carcinoma worldwide: bimodality in low-risk populations and aetiologic implications, Canc. Epidemiol. Biomarkers Prev. 17 (9) (2008) 2356–2365.
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[3] C.W. Chow, S.N. Tabrizi, K. Tiedemann, et al., Squamous cell carcinomas in children and young adults: a new wave of a very rare tumor? J. Pediatr. Surg. 42 (12) (2007) 2035–2039. [4] F. Siddiqui, R. Sarin, J.P. Agarwal, et al., Squamous carcinoma of the larynx and hypopharynx in children: a distinct clinical entity? Med. Pediatr. Oncol. 40 (5) (2003) 322–324. [5] V. Bhanuprasad, S. Mallick, S. Bhasker, et al., Pediatric head and neck squamous cell carcinoma: report of 12 cases and illustrated review of literature, Int. J. Pediatr. Otorhinolaryngol. 79 (8) (2015) 1279–1282. [6] M.V. Raval, K.Y. Bilimoria, A.K. Stewart, et al., Using the NCDB for cancer care improvement: an introduction to available quality assessment tools, J. Surg. Oncol. 99 (8) (2009) 488–490. [7] J.T. Albright, A.K. Topham, J.S. Reilly, Pediatric head and neck malignancies: US incidence and trends over 2 decades, Arch. Otolaryngol. Head Neck Surg. 128 (6) (2002) 655–659. [8] V.B. Prasad, S. Mallick, A.D. Upadhyay, et al., Systematic review and individual
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[12]
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patient data analysis of pediatric head and neck squamous cell carcinoma: an analysis of 217 cases, Int. J. Pediatr. Otorhinolaryngol. 92 (2017) 75–81. D.A. Palma, National cancer data base: an important research tool, but not population-based, J. Clin. Oncol. (2016) JCO2016692855. J.S. Cooper, K. Porter, K. Mallin, et al., National Cancer Database report on cancer of the head and neck: 10-year update, Head Neck 31 (6) (2009) 748–758. L.G. Morris, S.G. Patel, J.P. Shah, et al., Squamous cell carcinoma of the oral tongue in the pediatric age group: a matched-pair analysis of survival, Arch. Otolaryngol. Head Neck Surg. 136 (7) (2010) 697–701. V. Uloza, N. Ulozaite, S. Vaitkus, et al., Spontaneous regression of laryngeal carcinoma in 10 year old boy: a case report and review of literature, Int. J. Pediatr. Otorhinolaryngol. 103 (2017) 10–13. G.V. Walker, S.H. Giordano, M. Williams, et al., Muddy water? Variation in reporting receipt of breast cancer radiation therapy by population-based tumor registries, Int. J. Radiat. Oncol. Biol. Phys. 86 (4) (2013) 686–693.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Pediatric head and neck squamous cell carcinoma: Patient demographics, treatment trends and outcomes
T
Ankit Modha, Omar H. Gayarb, Mohamed A. Elshaikha, Arnold C. Paulinoc, Farzan Siddiquia,∗ a
Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI, USA Department of Radiation Oncology, Karmanos Cancer Institute - McLaren Flint, Flint, MI, USA c Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA b
A R T I C L E I N F O
A B S T R A C T
Keywords: Pediatric cancer Head and neck cancer Treatment outcomes Trends NCDB
Objectives: To examine patient demographics, temporal and treatment trends, and survival outcomes of pediatric non-nasopharyngeal head and neck squamous cell carcinomas using the National Cancer Database. Methods: The National Cancer Database was queried for pediatric patients (age 0–19 years) diagnosed with squamous cell carcinoma of the head and neck (including oral cavity, oropharynx, nasal cavity, larynx, hypopharynx, and salivary glands) from 2004 to 2013. Results: Of 159 patients identified, the majority had oral cavity SCC (55%). There was no discernable change in incidence trends over the study period with the number of cases per year ranging from 10 to 20 (R2 = 0.174). The predominant treatment regimen for the nasal cavity was trimodality (surgery, radiation, and chemotherapy) treatment (29%), chemotherapy and radiation for the oropharynx (40%), and surgery alone for salivary gland (47%), oral cavity (44%), and larynx (22%). The 5-year overall survival for the entire cohort was 74% and by subsite: oral cavity (66%), oropharynx (68%), nasal cavity (75%), and larynx (95%). Laryngeal disease had statistically significant longer survival when compared to oral cavity (p = .031) or oropharynx (p = .029). Conclusion: Although pediatric non-nasopharyngeal head and neck squamous cell carcinomas are rare, practitioners should be aware of this entity and consider it in the differential diagnosis of pediatric malignancies.
1. Introduction
2. Methods
Head and neck squamous cell carcinomas (SCC) are common in adults but considered very rare in the pediatric population. However, there is evidence of rising incidence of pediatric head and neck cancer [1], which is concerning considering little is known about the characteristics of this malignancy in this population. While nasopharyngeal carcinoma appears to have a bimodal distribution of cases ranging from the young to the elderly [2], non-nasopharyngeal SCC is very uncommon with most studies limited to case reports or small series [3,4]. There is limited information regarding appropriate management and care of these patients and most approaches are extrapolated from adult head and neck SCC [5]. Because paucity of information is available for this rare entity, we used the National Cancer Database (NCDB) to examine temporal and treatment trends as well as survival outcomes of pediatric non-nasopharyngeal HNSCC.
This retrospective study utilized the NCDB, which is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The clinical oncology outcomes database is sourced from hospital registry data collected in more than 1500 Commission on Cancer accredited facilities presenting nearly 70% of all new invasive cancer diagnoses in the US each year [6]. The use of this database is exempt from institutional review board authorization. The NCDB was queried for pediatric (age 0–19 years) patients diagnosed with SCC of the head and neck of all stages (including oral cavity, oropharynx, nasal cavity, larynx, hypopharynx, and salivary glands). Patients with incomplete or missing follow-up were excluded. Only histology codes for carcinoma, not otherwise specified; carcinoma, undifferentiated, not otherwise specified; SCC, not otherwise specified; and lymphoepithelial carcinoma (8010, 8020, 8070-8071, and 80828083) were included. Patient demographics and treatment characteristics were evaluated. Linear regression was used to evaluate the trends in the number of cases by year of diagnosis. Kaplan-Meir plots for overall survival were
∗
Corresponding author. Department of Radiation Oncology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. E-mail address: [email protected] (F. Siddiqui).
https://doi.org/10.1016/j.ijporl.2017.12.032 Received 30 October 2017; Received in revised form 26 December 2017; Accepted 29 December 2017 Available online 03 January 2018 0165-5876/ © 2018 Published by Elsevier B.V.
International Journal of Pediatric Otorhinolaryngology 106 (2018) 21–25
A. Modh et al.
Table 1 (continued)
Table 1 Patient characteristics of the study cohort of 159 patients with pediatric head and neck cancer. Characteristic
Characteristic 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
No. of Patients (%)
Age at diagnosis, years Median (range) 0-4 5-10 11-15 16-19
17 (0–19) 9 (6%) 14 (9%) 35 (22%) 101 (63%)
No. of Patients (%) 20 14 19 10 15 14 16 13 17 11
(13%) (9%) (12%) (13%) (9%) (9%) (10%) (8%) (11%) (7%)
Sex Male Female
FOM, floor of mouth; NCDB, National Cancer Database; NOS, not otherwise specified; SCC, squamous cell carcinoma.
96 (61%) 63 (39%)
generated and log-rank tests were used to evaluate outcomes across the cohort and stratified by subsite.
Race White Black Other
128 (81%) 17 (11%) 14 (8%)
3. Results
Site Lip FOM Gum Palate Tongue Larynx Hypopharynx Parotid gland Other salivary gland Tonsil Oropharynx Pharynx Nasal cavity Other (oral cavity, NOS)
We identified a total of 159 patients from 2004 to 2013. There was a male predominance (61%) with the median age of 17 years (range 0–19). Sixty-three percent of the patients were adolescents aged 16–19 years. Table 1 details the patient demographics. The majority of patients had disease in the oral cavity (55%). Additionally, 14% had a laryngeal primary, 13% in the nasal cavity, 11% in the salivary gland, and 6% with oropharyngeal tumors as well as 1 case in the hypopharynx. The most common stage grouping was stage IV (33%). There was a steady number of cases per year, ranging from 10 to 20 per year, without any discernable increase or decrease (R2 = 0.174). The 5-year overall survival for the entire cohort was 74% (Fig. 1) and by subsite (Fig. 2): oral cavity (66%), oropharynx (68%), nasal cavity (75%), and larynx (95%). Laryngeal disease had statistically significant longer survival when compared to oral cavity (p = .031) or oropharynx (p = .029). Table 2 details the treatment characteristics by head and neck subsite. The predominant treatment regimen for the oral cavity was surgery alone (44%). The nasal cavity was treated equally (29%) with chemotherapy and radiation as well as trimodality treatment. Laryngeal cancers were treated equally (22%) with surgery alone or chemotherapy and radiation. The one case of hypopharyngeal cancer was treated with radiation alone. Forty percent of oropharyngeal cancers were treated with chemotherapy and radiation and 47% of salivary gland cancers were treated with surgery alone.
8 (5%) 3 (2%) 10 (6%) 6 (4%) 57 (36%) 22 (14%) 1 (< 1%) 10 (6%) 7 (4%) 6 (4%) 2 (1%) 2 (1%) 21 (13%) 4 (3%)
Site (sorted) Oral cavity Oropharynx Nasal cavity Larynx Hypopharynx Salivary gland
88 (55%) 10 (6%) 21 (13%) 22 (14%) 1 (< 1%) 17 (11%)
Histology Carcinoma, NOS Papillary SCC SCC, NOS SCC, keratinizing SCC, non- keratinizing Lymphoepithelial carcinoma Basaloid SCC
16 (10%) 5 (3%) 93 (59%) 24 (15%) 7 (4%) 4 (3%) 10 (6%)
NCDB Analytic Stage Group 1 2 3 4 Unknown
48 17 18 52 24
(30%) (11%) (11%) (33%) (15%)
33 53 31 14 28
(21%) (33%) (19%) (9%) (18%)
Grade Well differentiated Moderately differentiated Poorly differentiated Undifferentiated Unknown Year of diagnosis Fig. 1. Kaplan-Meir plot for overall survival for the entire study cohort.
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and 1 larynx. The 1 patient with low-risk HPV had cancer of the pharynx. 4. Discussion We present one of the largest series of pediatric head and neck nonnasopharyngeal SCC. Reassuringly, the annual number of cases identified remained steady across the study period. In their analysis of Surveillance, Epidemiology, and End Results data, Albright et al. identified 3050 pediatric head and neck tumors from 1973 to 1996, with histologies ranging from lymphomas, sarcomas, and adenocarcinomas, amongst many others. They found an increased incidence of head and neck malignancies in patients younger than 15 years old when comparing the incidence of pediatric cancers as a whole over that time period. Pediatric cases of SCC in that series, however, accounted for less than 2% (54) of patients [7]. While the data presented here is from a different national database, there were more cases identified in our series over a shorter time period. There are no universally accepted treatment guidelines due to the rarity of pediatric head and neck cancers. The treatment patterns of these malignancies in our series mirror those of their adult subsite counterparts. While there is limited information in our cohort to make inferences of treatment on survival, in their systematic review with individual patient data of 217 cases of pediatric HNSCC, Bhanu Prasad et al. revealed a favorable survival for patients treated with surgery alone or surgery followed by adjuvant radiation. The patterns of care delivered in their study also reflected those of adult patients with HNSCC [8]. Six patients, however, did not receive any treatment in our series. This may reflect a limitation of the database rather than actual nontreatment. The cohorts are hospital-based and not population-based.
Fig. 2. Kaplan-Meir plot for overall survival stratified by head and neck subsite. The one case of hypopharyngeal cancer was included with the laryngeal cohort.
Additional pathologic and tumor characteristics of the study cohort are presented in Table 3. When surgery was performed, the majority of patients had negative margins and no residual tumor present (52%). Of these, the most common pathologic TMN stage group was I (20%). Of 19 patients who had Human Papilloma Virus (HPV) testing, 6 patients were positive for high risk subtypes (16 or 18) and 1 patient was positive with low-risk subtypes. These patients represent 4% (7 of 159) of the entire cohort or 37% (7 of 19) of those tested. Of the high risk subtypes, 3 were cancers of the oral cavity, 1 pharynx, 1 nasal cavity,
Table 2 Treatment characteristics. Surgery
None Biopsy/local excision Radical excisiona Surgery, NOS
Oral Cavity (n = 88)
Oropharynx (n = 10)
Nasal Cavity (n = 21)
Larynx/Hypopharynxb (n = 23)
Salivary Gland (n = 17)
N (%)
N (%)
N (%)
N (%)
N (%)
15 (17%) 8 (9%) 62 (71%) 3 (3%)
6 (60%) 2 (20%) 2 (20%) 0
9 (43%) 5 (24%) 7 (33%) 0
12 (52%) 8 (35%) 1 (4%) 2 (9%)
2 (12%) 5 (29%) 10 (59%) 0
41 (47%) 42 (48%) 1 (1%) 1 (1%) 3 (3%)
2 (20%) 7 (70%) 0 0 1 (10%)
7 (33%) 13 (62%) 0 1 (5%) 0
9 (39%) 13 (57%) 0 1 (4%) 0
8 (47%) 9 (24%) 0 0 0
55 (63%) 30 (34%) 3 (3%)
1 (10%) 8 (80%) 1 (10%)
8 (38%) 13 (63%) 0
14 (61%) 9 (39%) 0
13 (76%) 4 (24%) 0
1 0 0 0 0 1 4 3 1
2 4 0 1 2 0 6 6 0
2 5 4 1 3 1 5 2 0
0 8 0 0 5 0 2 2 0
Radiation None EBRT Brachytherapy Radiation, NOS Unknown Chemotherapy None Administered Unknown
Combined modality treatment No therapy Surgery alone RT alone CT alone S + RT S + CT CT + RT S + RT + CT Unknown
1 (1%) 39 (44%) 0 1 (1%) 14 (16%) 0 13 (15%) 16 (18%) 4 (4%)
(10%)
(10%) (40%) (30%) (10%)
(9%) (19%) (5%) (9%) (29%) (29%)
CT, chemotherapy; EBRT, external beam radiation therapy; NOS, not otherwise specified; RT, radiation; S, surgery. a Includes glossectomy, pharyngectomy, laryngectomy, or parotidectomy when specified. b The one case of hypopharyngeal cancer was treated with radiation alone.
23
(9%) (22%) (17%) (4%) (13%) (4%) (22%) (9%)
(47%)
(29%) (12%) (12%)
International Journal of Pediatric Otorhinolaryngology 106 (2018) 21–25
A. Modh et al.
elsewhere. An advantage of the NCDB over other registry data is that it captures approximately 70% of all incident cancers in the US and includes more complete information on treatment, such as radiation dose/target and chemotherapy data [6]. There are 111 pediatric hospitals that contribute data to the NCDB, including St. Jude Children's Research Hospital, Texas and Boston Children's Hospitals. The patients in our study had a favorable long-term survival when compared to survival for adult head and neck SCC [10]. Bhanuprasad et al. presented their experience treating 12 cases of head and neck SCC, most of which were also of the oral cavity. Of the evaluable patients, all patients were surviving at last follow-up without disease (with a median follow-up of 2 years) [5]. An aged-matched group of 10 pediatric patients with oral tongue SCC treated at Memorial Sloan-Kettering Cancer Center reported an equivalent 5-year overall survival (70% in the pediatric group and 64% in the adult group) [11]. The laryngeal patients in our cohort also had very good overall survival. Over 50% of the laryngeal patients in our cohort had early stage disease, which may explain this favorable outcome. Siddiqui et al. reported 6 patients with SCC of the larynx and hypopharynx. Of these, 3 patients with laryngeal primaries had their disease controlled at last follow-up [4]. Additionally, there may be different etiologic origins of the disease in the larynx of pediatric patients. Two of the 3 larynx patients in another case series were HPV-16 positive [3], which is uncommon in the adult laryngeal cancer population, the majority of which is smoking and alcohol related. There were 7 patients in our cohort which were HPV positive, although only a limited number had HPV testing. Of these only 2 patients had oropharyngeal cancer, where this virus is typically correlated with in the adult population. Additionally, a recent case report discussed a case of spontaneous regression of a 10-year old patient with laryngeal carcinoma which was HPV-26 positive, which is not typically oncogenic [12]. This analysis of a large hospital-based registry has a number of limitations, including inherent biases of retrospective analyses. Registry data have been shown to report variable rates of actual treatment delivered [13]. Additionally, the NCDB lacks data on recurrence patterns, treatment toxicity, and etiologic factors such as smoking, all of which are very relevant for this patient population.
Table 3 Additional pathologic and tumor characteristics of the study cohort. Characteristic
No. of Patients (%)
AJCC (TMN) Clinical Stage I II III IV, NOS IVA IVB IVC Unknown
39 (24%) 25 (16%) 12 (8%) 2 (1%) 36 (23%) 4 (2%) 1 (1%) 40 (25%)
AJCC (TMN) Pathological Stage I II III IV, NOS IVA IVB IVC Unknown
32 (20%) 11 (7%) 11 (7%) 1 (1%) 23 (14%) 1 (1%) 1 (1%) 79 (49%)
Tumor Size Microscopic only 4-20 mm 21-40 mm 41-60 mm 61-80 mm 81-100 mm 150 mm 480-500 mm Described as less than Described as less than Described as less than Described as less than Described as less than Unknown
1 cm 2 cm 3 cm 4 cm 5 cm
2 (1%) 42 (26%) 41 (25%) 10 (6%) 4 (2%) 3 (2%) 1 (1%) 2 (1%) 1 (1%) 2 (1%) 0 (0%) 1 (1%) 2 (1%) 48 (29%)
Surgical Margins No residual tumor Residual tumor, NOS Microscopic residual Macroscopic residual Not evaluable No surgery Unknown
83 (52%) 4 (2%) 7 (4%) 1 (1%) 6 (4%) 44 (28%) 14 (9%)
5. Conclusion In conclusion, the number of cases of pediatric non-nasopharyngeal head and neck SCC remained steady over the study period. Although rare, practitioners should be aware of this entity and consider it in the differential diagnosis of pediatric malignancies.
Pathologic Nodal ECE
Funding No nodal involvement Nodal involvement, no ECE ECE present Nodes not collected, FNA, or information not collected Unknown
16 (10%) 7 (4%) 4 (3%) 121 (76%) 11 (7%)
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflicts of interest
HPV Status Negative Positive for low-risk types Positive for high-risk types Not collected or not done Unknown
The authors declare no conflicts of interest.
12 (7%) 1 (1%) 6 (4%) 114 (72%) 26 (16%)
Presentations Accepted for presentation at the 2018 Multidisciplinary Head and Neck Cancers Symposium, Scottsdale, Arizona, February 2018.
AJCC, American Joint Committee on Cancer; ECE, extracapsular extension; HPV, Human Papilloma Virus; NOS, not otherwise specified; TMN tumor, node and metastasis.
References They are identified from the hospitals where they present for diagnosis and/or treatment, and the potential exists for patients to be diagnosed at a participating hospital but treated at a facility not participating or contributing to the NCDB [9]. Four of the 6 patients had their initial diagnosis at the reporting facility and part or all of their treatment
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