September 2019 HSC Section 1 Congenital and Pediatric Problems

ZAMANI ET AL .

Pediatric salivary gland cancer primary and adjuvant treatment distribution

TAB L E 2

Parotid surgery

Surgery total (%)

Surgery only (%)

Adj. radiation (%)

Neck dissection (%)

Other a (%)

PP (%)

TP/RRx (%)

FNRx (%)

Authors

Rebours et al

11.6

97.6

62.8

25.5

39.5

8.3

86.1

13.9

Mao et al b

0

100

0

100

0

0

100

0

Radomski et al

3.7

96.3

60.4

35.9

–

56.9

40.8

16.6

Locati et al

0

100

79.3

20.7

–

40.9

59.1

–

Qureshi et al

0

100

62.5

37.5

29.2

18.8

81.3

50

Cockerill et al

12.5

91

82.1

5.4

39.3

33.3

66.7

–

Fang et al

11.8

88.2

82.4

5.9

11.8

100

0

23.1

Liu et al

7.7

92.3

61.5

30.8

7.7

50

50

16.7

Aro et al

0

100

90

10

10

75

25

–

Galer et al

31.4

71.4

54.3

14.3

–

–

–

–

Kupferman et al

4.9

98.4

52.5

42.6

68.9

66.7

33.3

2

Laikui et al

0

100

84.2

15.8

36.8

22.2

77.8

–

Ellies et al

0

100

100

0

16.7

8.3

91.7

33.3

Whatley et al

0

100

45.5

54.5

36.4

66.7

33.3

11.1

Ribeiro et al

11.1

100

63

25.9

37

20

80

20

Yu et al

17.4

82.6

82.6

0

4.4

30.8

69.2

46.2

Hicks and Flaitz

19.2

100

80.8

0

–

–

–

–

Weighted average (95% CI) 17.5 (16.3– 18.6) Adj., adjuvant; PP, partial parotidectomy; TP, total parotidectomy; RRx, radical resection; FNRx, facial nerve resected; CI, confidence interval. a It includes palliation, adjuvant chemotherapy ( ± radiotherapy), primary chemo/radiotherapy, unspecified and no treatment. b In this study, childrenwere treated postoperatively with brachytherapy instead of conventional radiotherapy andwere not included in theweighted average for adjuvant radiotherapy. 7.7 (7.2–8.3) 94.7 (94.2–95.2) 64.5 (63.2–65.7) 24.3 (23.2–25.5) 32.2 (30.0–34.5) 44.7 (42.8–46.6) 53.9 (52.1–55.9)

minor salivary glands (14%; n = 13). The third most common type was AdCC in the parotid glands (5%; n = 21), AciCC in the submandibular glands (9%; n = 4), and adenocarcinoma (not otherwise specified) in the minor salivary glands (9%; n = 9) (Figure 2, Supporting Information Tables S2 and S3). 11,13,14,16–22,24–28 Grade of differentiation was only available for MEC, in a total of 11 studies ( n = 182). Overall, 87% of the SGCs were of low/intermediate grade ( n = 158) and 10%were of high grade ( n = 18) (Supporting Infor- mation Table S4). 11,12,14–16,21,24–27,29 TNM stage was only available for MEC, in a total of eight studies ( n = 142); six studies had available T-stage ( n = 110), 72% were T1/T2 ( n = 63), and 23%were T3/4 ( n = 13). Five studies had availableN-stage for MEC ( n = 93) and 11%were N + ( n = 10). All cases of MEC were M0 at time of diagnosis (Supporting Information Table S4). 11,12,14,15,21,24,27 Follow-up was available in 95% of cases ( n = 693) with a mean/median follow-up of 7.9/6.7 years (95% CI: 7.5-8.3 years/6.4-6.9 years). At last follow-up, 93% of the children were alive ( n = 647). Seventeen stud- ies reported on recurrence of SGC ( n = 422) and recurrences were observed in 20% of the children ( n = 83) after a median time of 1.1 years (95% CI: 0.9-1.3 years). In seven of 19 studies ( n = 233), 5-year overall survival was 94%. In six of 19 studies ( n = 210), 5-year disease- free survival was 83% (Table 3). 11–18,20–30 3.4 Outcome

4 DISCUSSION

In this systematic review and meta-analysis, our aimwas to investigate the characteristics, tumor histopathology, treatment, and survival of children with SGC by combining all available, recent, and larger case series. In children with SGC, we observed an overall ratio of 1.4:1, match- ing the F:M ratio found in children with benign tumors of the salivary glands. 4,8 The median age at diagnosis for children with SGC was 14.2 years, being slightly younger than for children with benign salivary gland tumors. 8 The most common tumor site was the parotid gland, which is similar to the general population. 31 Children were referred to university hospitals or tertiary cancer centers in most studies, usu- ally with a solid palpable mass as their only symptom. One-fifth of the children experienced pain in conjunction with palpable masses, however facial nerve involvement was rare, which is in agreement with previous reviews. 4 Previous reviews note that children experi- ence symptoms of salivary gland masses for at least 8-12 months prior to diagnosis. 1,4,8 Furthermore, with fine needle cytology, there is a risk of misdiagnosing masses as benign tumors, when they are in fact malignant. 11 It is, therefore, important to assess children with sali- vary gland masses in specialized cancer centers, where a combination of ultrasound-guided fine needle aspiration cytology, magnetic res- onance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) is available. Additional perioperative frozen

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