September 2019 HSC Section 1 Congenital and Pediatric Problems

ZAMANI ET AL .

Follow-up and survival of pediatric salivary gland cancer

TAB L E 3

Patients available for follow-up

Disease-free survival (5-year)

Overall survival (5-year)

Mean/median follow-up,

Median time to recurrence,

Alive at follow-up

Recurrence

Authors

(%)

years (range)

(%)

years (range)

(%)

(%)

(%)

Rebours et al

97.7

4.8 (0.1–23.5)

14.3

1.1 (0.8–12.5)

97.6

60

100

Mao et al

100

7.2 (5–13.4)

0

–

100

100

100

Radomski et al

100

5

–

–

95.5

–

–

Locati et al

100

7.3/7 (3–18)

6.9

1.7 (1.7–1.8)

100

–

–

Xu et al

78.9

4.8 (0.2–19.1)

16.7

1.4 (1.3–5.9)

96.7

83

96

Qureshi et al

100

3.8 (0.8–7.3)

4.2

2.9 (2.9–2.9)

100

91.7

100

Cockerill et al

100

14 (0.2–62.3)

30.4

0.8 (0.2–45)

92.9

–

–

Fang et al

100

(2–21.5)

35.3

–

76.5

–

–

Liu et al

69.2

2.5 (1.4–5.1)

44.4

1.0 (0.6–2.5)

66.7

–

–

Aro et al

100

3.1 (0.4–14)

0

–

100

–

–

Galer et al

100

–

11.4

–

91.4

88.4

89.3

Kupferman et al

100

9.5

26.2

–

88.5

85

93

Laikui et al

78.9

4.8 (0.3–10)

13.3

3.5 (3–4)

86.7

–

–

Ellies et al

100

(0.5–16.5)

8.3

1.0 (1–1)

66.7

–

–

Whatley et al

91.7

6.6/6 (3–13)

18.2

–

100

–

–

Ribeiro et al

100

17.5 (1.8–40.3)

25.9

0.7 (0.2–26.4)

77.8

–

81.6

Yu et al

65.2

8 (1–23)

33.3

–

93.3

–

–

Hicks and Flaitz

100

9

–

–

92.3

–

–

Weighted average (95% CI) 94.2 (93.5–94.9) This outlines follow-up characteristics, including recurrence rate, 5-year disease-free survival, and overall survival in children with salivary gland cancer. CI, confidence interval. 95.4 (94.6–96.1) 7.9 (7.5–8.3)/ 6.7 (6.4–6.9) 19.8 (18.8–20.8) 1.1 (0.9–1.3) 92.8 (92.2–93.3) 82.7 (81.1–84.3)

negative surgical margins had fewer recurrences. 22,23 To reduce the risk of tumor seeding and recurrences, fine needle aspiration cytology supported by perioperative frozen sections to confirm the diagnosis may be sufficient, and postoperative MRI and PET-CT controls to ensure that no tumor tissue remains. Five-year overall- and disease-free survival in pediatric SGC was excellent in studies that assessed survival. Radomski et al found a lower 5-year overall survival ( ∼ 84%) with adjuvant radiotherapy in children versus surgery as the only treatment modality ( ∼ 98%). 13 However, the authors did not adjust for tumor grade or stage, which is important considering adjuvant radiotherapy is often reserved for highly aggres- sive or recurrent tumors. 4,5,8 Of the seven studies that estimated 5-year overall survival, four studies had a survival less than 100%. These deaths were often due to recurrences of the primary tumor. Three of the studies found significant correlations between high tumor grade and lower survival. 22,23,27 Adjuvant radiotherapy is known to cause long-term complications such as added risk of sec- ondary cancers, facial deformity, dental complications, and permanent xerostomia. 23 In an alternative approach, Mao et al treated 24 children with advanced or recurrent MEC of the parotids using brachyther- apy; all children were alive without disease after a median follow-up of 7.2 years (range 5–13.4 years). 12 This may prove to be an interest- ing alternative to external beam radiation in children, considering the lower dose of radiation to adjacent structures with brachytherapy. 12

Some studies have observed that childhood survivors of cancer treated with external beam radiotherapy or chemotherapy had increased risk of developing secondary MEC. 11,26,34 Vedrine et al reported on 11 children with secondary MEC, where they observed a mean latency period of 5.5 years from the primary cancer, and no difference in sur- vival compared to children with primary MEC. 34 Thariat et al note that 6% of secondary cancers in children are salivary gland MEC and that risk factors include radiotherapy, anthracyclines, epipodophyllotoxine, and alkylating agents. 35 In the studies included in this review, primary and adjuvant chemotherapies were rarely used, mostly in palliation. 21 This was possibly due to the low rate of disseminated SGC in children. In conclusion, we reported on 749 children with SGC and found a median age at diagnosis of 14.2 years and a F:M ratio of 1.4:1. Lower grade and low-stage parotid gland MEC was the most frequent sub- type. Children with persistent palpable masses in the salivary glands must be referred to specialized cancer centers, where ultrasound- guided fine needle aspiration cytology and magnetic resonance imag- ing should be performed. Primary surgery with perioperative frozen sections is advised to confirm the histopathology and margin con- trol, and the option for facial nerve reconstruction should be available in case of nerve involvement. Adjuvant treatment must be discussed in multidisciplinary teams on a case-by-case level, as very few chil- dren have metastatic disease. Due to the risk of recurrence, frequent

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