Mortality of uveal melanoma in children and adolescents from 2004 to 2020

Abstract

Purpose

To analyze epidemiological factors, tumor characteristics, and mortality rates in a cohort of pediatric patients with uveal melanoma (UM) from the National Cancer Database (NCDB).

Methods

In this retrospective cohort study, patients ≤20 years of age in the NCDB diagnosed with UM were included. Patients were identified using ICD-10 and ICD-O-3 codes. Main outcome measures were demographics, clinical features, and overall survival. Mortality was assessed using Kaplan-Meier survival analysis and Cox logistic regression. Significance was defined as P < 0.05.

Results

Of 129 patients (68 females) included, mean age at diagnosis was 15.9 years. Most patients were White (91.5%), followed by Black (3.1%), and other races (5.4%). Tumors were primarily in the choroid (75.2%), followed by ciliary body (13.2%) or iris (7.0%). Kaplan Meier overall survival at 5-,10-, and 15-years was 93.6%, 80.3%, and 63.4%, respectively. Survival was worse with more advanced tumor T category (10-year survival 73.8% for cT1, 82.6% for cT2, 0% for cT4 [P = 0.022]) and American Joint Committee on Cancer stage (15-year survival 61.9% for stage I vs 45.5% for stage III [P < 0.001]). Cox logistic regression analysis identified older age at presentation (OR = 1.618, P = 0.036) and non-White race (OR = 21.39, P = 0.045) as significant predictors of mortality.

Conclusions

In our study cohort, older age, non-White race, and advanced tumor stage at diagnosis were associated with increased mortality in children and adolescents with UM. Adolescents have a similar prognosis to adults, whereas children have more favorable outcomes.

Uveal melanoma (UM) is a rare, aggressive cancer arising from melanocytes in the eye’s uveal tract, which includes the choroid, ciliary body, and iris. UM is the most common primary intraocular malignancy in adults, with an average age of presentation of 60 years old and an age-adjusted incidence of 5.1 per million in the United States.¹ Singh and colleagues² found that the 5-year survival rate of UM in adults was 81.6%.

Although incidence and survival rates of UM have been widely studied in adults, they have not been well studied in children, owing to its rarity in this population. In a large study of 8,033 cases, only 1% were patients ≤20 years of age.³ Research on the long-term mortality rates of pediatric UM is sparse. We present, to our knowledge, the largest retrospective review of UM in the pediatric population. Our study focuses on analyzing epidemiological factors, tumor characteristics, and mortality rates based on a cohort of pediatric patients from the National Cancer Database (NCDB).

Subjects and Methods

This retrospective analysis was performed on patients diagnosed with UM from 2004 to 2020 using the National Cancer Database (NCDB). The NCDB is a collaborative initiative between the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. It serves as a nationwide oncology outcomes database for over 1,500 commission-accredited cancer programs across the United States and Puerto Rico, reporting about 72% of all newly diagnosed cancer cases at the institutional level. Because the database provides only deidentified information, this study was exempted from requiring institutional review board approval. Insight into the composition of NCDB, data collection strategies, and inclusion criteria has been provided in previous studies.⁴

Cases of UM were identified by first categorizing uveal pathologies using primary site ICD-10 codes C69.3 (choroid) and C69.4 (iris and ciliary body). ICD-O-3 histology codes 8720–8790 were then used to specifically address melanomas. Thereafter, NCDB site-specific factor 25 was utilized to distinguish between melanoma of the iris and melanoma of the ciliary body. Patients with missing information, including age at diagnosis, sex, and time in years from diagnosis to last follow-up were excluded. The cohort was further refined to include only children and adolescents (≤20 years of age).

Demographic information, including age at diagnosis, sex, race, ethnicity, and insurance status was extracted from the NCDB database. The Charlson-Deyo score was used as a measure of comorbidity burden for patients.⁵ Since the maximum score that was present in the cohort was 1, it is represented as a binary variable in our data. Further extraction was done for clinical features such as tumor location, laterality, tumor thickness, tumor basal diameter, American Joint Committee on Cancer (AJCC) staging, and clinical T staging. Treatment data, such as treatment type and time in years from diagnosis to treatment, as well as follow-up data, including age at last follow-up and follow-up duration and mortality, were also collected.

Age, tumor thickness, and tumor basal diameter were further subcategorized. Age was divided into subgroups <10 years and ≥10 years, based on the World Health Organization’s (WHO) definition of adolescence.⁶ Tumor thickness was separated, based on Shields and colleagues,⁷ into small (<2 mm), medium (2–8 mm), and large (>8 mm). Likewise, basal diameter was classified into small (<5 mm), medium (5–15 mm), and large (>15 mm) based on the distribution of our cohort.

The primary variable of interest was mortality, determined using the vital status variable from the NCDB database, which indicates “the patient’s vital status as of the date recorded in date of last contact or death.” Differences in the distribution of demographic and clinical factors between patients who were reported as deceased by the last contact and those who survived were analyzed.

Kaplan-Meier survival analysis was performed on the entire cohort using time-to-follow-up and vital status at the last follow-up. To establish time-to follow-up, we used the variable representing the number of months from diagnosis to the last contact or death. Missing data in this variable and the vital status variable were excluded from the analysis. The Kaplan-Meier estimator in SPSS was used to plot survival. This process was repeated to stratify survival based on primary tumor site, treatment status, age, clinical T categorization, AJCC staging, tumor thickness, tumor diameter, and sex. The χ² value, degrees of freedom, and P value from Mantel-Cox analyses are also included in these tables. To address confounders, Cox logistic regression was used and included variables that had adequate data, namely age, sex, race, ethnicity, primary site, laterality, clinical T staging, and AJCC staging (Table 3). All analyses were conducted using SPSS statistical software version 29.0.0.0 (IBM, Armonk, NY).

Table 3.

Cox logistic regression for risk factors for death

Study parameter	OR	95% CI		P value
		Lower	Upper
Age	1.618	1.031	2.54	0.036
Male Sex	4.777	0.614	37.155	0.135
Non-White Race	21.386	1.073	426.113	0.045
Hispanic ethnicity	10.836	0.409	287.327	0.154
Primary site of tumor
Choroid	Reference	—	—	—
Iris	0	0	2.96E+81	0.933
Ciliary body	0.575	0.075	4.393	0.594
Unknown	0	0	.	0.993
Right laterality	2.041	0.352	11.834	0.426
AJCC staging
I	Reference	—	—	—
II	4.214	0.027	654.096	0.576
III	0.405	0.004	44.726	0.707
IV	3.488	0.085	142.44	0.509
Unknown	267.173	5.948	11999.92	0.004
Clinical T staging
cT1	Reference	—	—	—
cT2	14.15	0.682	293.638	0.087
cT3	0	0	1.73E+68	0.912
cT4	2.154	0.014	326.222	0.764
cTX	6.298	0.055	724.102	0.447

AJCC, American Joint Committee on Cancer; CI, confidence interval; OR, odds ratio.

Results

There were 39,128 eye/orbit cases recorded from patients of all ages in the NCDB database between 2004 and 2020. Of these, 129 patients (68 females [52.7%]) met inclusion criteria. Mean age at diagnosis was 15.9 years (median, 17.0; range, 0.0–20.0). Of the 129 patients, 120 (93%) were aged 10 years or older, and 9 (7%) were younger than 10 years. Among those aged 10 years or older, 7 patients were between 10 and 12 years old. The racial distribution was predominantly White (n = 118 [91.5%]), followed by Black (n = 4 [3.1%]), and other races (n = 7 [5.4%]). Hispanic ethnicity was noted in 9 patients (7.0%). Insurance status varied; most patients had private insurance (n = 93 [72.1%]); others were covered by Medicaid (n = 21 [16.3%]), other government programs (n = 4 [3.1%]), were uninsured (n = 3 [2.3%]), or their insurance status was unknown (n = 8 [6.2%]). The comorbidity score was 1 in 7 patients (5.4%).

Clinically, the tumor was primarily located in the choroid (n = 97 [75.2%]), followed by the ciliary body (n = 17 [13.2%]) and the iris (n = 9 [7.0%]). Six cases (4.7%) had an unknown primary site and could be localized to either the ciliary body or iris because they fell under the ICD10 code C69.4. Laterality was 52.7% in the right eye (n = 68) and 47.3% in the left eye (n = 61). The mean tumor thickness was 5.04 mm (median, 3.70; range, 0.06–19.70); the mean tumor basal diameter, 7.53 mm (median, 5.90; range, 0.40–24.00 mm). AJCC tumor staging was stage I in 40 cases (31.0%), stage II in 44 (34.1%), stage III in 18 (14.0%), stage IV in 4 (3.1%), and unknown in 23 (17.8%). Clinical T categorization was cT1 in 45 cases (34.9%), followed by cT2 (n = 35 [27.1%]), cT3 (n = 15 [11.6%]), cT4 (n = 6 [4.7%]), and cTX (n = 28 [21.7%]).

For treatment, surgery was used alone in 28 cases (21.7%); radiation was used alone in 81 cases (62.8%). Radiation was used in combination with surgery in 10 cases (7.8%) (before surgery in 3, intraoperatively in 1, and after surgery in 6). Additionally, 10 patients (7.8%) received no treatment. The mean time from diagnosis to treatment initiation was 27.03 days (median, 20.50; range, 0.00–180.00).

The mean age at last follow-up was 22.10 years (median, 21.90; range, 3.70–36.10). The average duration from diagnosis to the last follow-up was 6.19 years (median, 5.43 years; range, 0.00–17.18).

When stratified by vital status at last follow-up, 115 patients (89.2%) were alive, and 14 (10.9%) were deceased. The mean age at diagnosis for survivors was 15.66 years (median, 17.0; range, 0.0–20.9), compared with 17.9 years (median, 18.0; range, 16.0–20.9) for those deceased. The mean age at last follow-up was 21.75 years (median, 21.5; range, 3.7–36.1) for survivors and 24.9 years (median, 24.5; range, 16.1–31.1) for the deceased. The average duration from diagnosis to last follow-up was 6.09 years (median, 5.43; range, 0.00–17.18) for survivors and 7.00 years (median, 7.49; range, 0.11–13.11) for deceased patients. Males were more prevalent among the deceased (n = 8 [57.1%]) compared with the surviving cohort (n = 53 [46.1%]). The remainder of the univariate analyses can be found in Table 1.

Table 1.

Demographic and clinical characteristics^a

Study parameter	Alive by last follow-up	Deceased by last follow-up	Total cohort
Demographics
Total	115 (89.2)	14 (10.9)	129 (100)
Age at diagnosis, years, mean (median; range)	15.66 (17.00; 0.00–20.00)	17.93 (18.00; 16–20)	15.91 (17.00; 0.00–20.00)
Sex
Male	53 (46.1)	8 (57.1)	61 (47.2)
Female	62 (53.9)	6 (42.9)	68 (52.7)
Race
White	106 (92.2)	12 (85.7)	118 (81.5)
Black	2 (1.7)	2 (14.3)	4 (3.1)
Other	7 (6.1)	0 (0.0)	7 (5.4)
Hispanic	8 (7.0)	1 (7.1)	9 (7.0)
Insurance status
Not insured	2 (1.7)	1 (7.1)	3 (2.3)
Private / managed care	83 (72.1)	10 (71.4)	93 (72.1)
Medicaid	19 (16.5)	2 (14.3)	21 (16.3)
Other government	4 (3.5)	0 (0.0)	4 (3.1)
Unknown	7 (6.1)	1 (7.1)	8 (6.2)
Charlson-Deyo	7 (6.1)	0 (0.0)	7 (5.4)
Comorbidity Index = 1
Clinical features
Location
Choroid	85 (73.9)	12 (85.7)	97 (75.2)
Iris	9 (7.8)	0 (0.0)	9 (7.0)
Ciliary body	15 (13.0)	2 (14.3)	17 (13.2)
Unknown	6 (5.2)	0 (0.0)	6 (4.7)
Laterality
Right eye	61 (53.0)	7 (50.0)	68 (52.7)
Left eye	54 (47.0)	7 (50.0)	61 (47.3)
Tumor thickness, mm, mean (median; range)	4.79 (3.45; 0.06–19.70)	7.12 (8.57; 0.65–12.00)	5.04 (3.70; 0.06–19.70)
Tumor base diameter, mm, mean (median; range)	7.53 (5.60; 0.40–24.00)	7.44 (6.50; 1.10–19.00)	7.53 (5.90; 0.40–24.00)
AJCC staging
I	37 (32.2)	3 (21.4)	40 (31.0)
II	41 (35.7)	3 (21.4)	44 (34.1)
III	15 (13.0)	3 (21.4)	18 (14.0)
IV	1 (0.9)	3 (21.4)	4 (3.1)
Unknown	21 (18.3)	2 (14.3)	23 (17.8)
Clinical T staging
cT1	43 (37.4)	2 (14.3)	45 (34.9)
cT2	31 (27.0)	4 (28.6)	35 (27.1)
cT3	15 (13.0)	0 (0.0)	15 (11.6)
cT4	4 (3.5)	2 (14.3)	6 (4.7)
cTX	22 (19.1)	6 (42.9)	28 (21.7)
Treatment
Surgery only	23 (20.0)	5 (35.7)	28 (21.7)
Radiation only	74 (64.4)	7 (50.0)	81 (62.8)
Surgery and radiation together	10 (8.7)	0 (0.0)	10 (7.8)
Radiation before surgery	3 (30.0)	0 (0.0)	3 (2.3)
Radiation after surgery	6 (60.0)	0 (0.0)	6 (4.7)
Intraoperative radiation	1 (10.0)	0 (0.0)	1 (0.8)
No treatment	8 (7.0)	2 (14.3)	10 (7.8)
Time, years, from diagnosis to treatment initiation, mean (median; range)	26.88 (21.00; 0.00–180.00)	28.42 (16.00, 0.00–158.00)	27.03 (20.50, 0.00–180.00)
Follow-up
Age, years, at last follow-up, mean (median; range)	21.75 (21.53, 3.73–36.14)	24.93 (24.49, 16.11–31.11)	22.10 (21.89, 3.73–36.14)
Follow-up duration, years, mean (median; range)	6.09 (5.43, 0.00–17.18)	7.00 (7.49 (0.11–13.11)	6.19 (5.43, 0–17.18)

AJCC, American Joint Committee on Cancer.

^aResults are in the form number (%) unless otherwise indicated.

Kaplan-Meier survival estimates are highlighted in Table 2. Cumulative survival rates for UM were 93.6% at 5 years, 80.3% at 10 years, and 63.4% at 15 years. Choroidal melanomas had the worst survival rate (53.2% at 15 years [log-rank P = 0.536]) (Figure 1). Among treatment groups, patients undergoing surgery alone had the worst 15-year survival (46.7%), followed by radiation only (72.3%), and combined surgery and radiation (100%) (log-rank P = 0.092). Age-stratified analysis showed that children (<10 years) had a 15-year survival of 100%, while adolescents (≥10 years) had a lower survival of 60.8% (log-rank P = 0.252). By 10 years, survival by clinical staging was highest in the cT2 category (82.6%) and lowest in cT4 (0%) (log-rank P = 0.022). Survival rates by AJCC staging at 5 years were 92.9% for stage I, 93.5% for stage II, 90.9% for stage III, and 75.0% for stage IV. At 10 years, survival declined to 77.4% for stage I, 84.1% for stage II, 68.2% for stage III, and 37.5% for stage IV. By 15 years, survival remained 61.9% for stage I and 45.5% for stage III, while estimates for stage II and stage IV were unavailable due to limited follow-up (log-rank P < 0.001). Cox logistic regression analysis, detailed in Table 3, identified significant predictors of death at last follow-up. Older age at presentation (OR 1.618, P = 0.036) and non-White race (OR = 21.386, P = 0.045) were significant predictors.

Table 2.

Kaplan Meier survival estimates for 5-, 10-, and 15-year periods stratified by tumor site, treatment type, age, AJCC staging, clinical T category, thickness in mm, diameter (mm), and sex

	% survival ± SE			P value
	5 years	10 years	15 years
Tumor site				0.536
Iris	100.0 ± 0.0	100.0 ± 0.0	100.0 ± 0.0
Ciliary body	92.9 ± 6.9	84.4 ± 10.2	-
Choroid	92.9 ± 3.2	76.0 ± 8.3	53.2 ± 12.5
Uveal melanoma (all sites)	93.6 ± 2.6	80.3 ± 6.2	63.4 ± 10.0
Treatment type				0.092
Surgery only	84.0 ± 8.7	70.0 ± 14.7	46.7 ± 21.4
Radiation only	93.2 ± 3.4	81.4 ± 8.6	72.3 ± 11.5
Surgery and radiation	100	100	100
Age				0.252
<10 years old (children)	100 ± 0	100 ± 0	100 ± 0
≥10 years old (adolescents)	93.0 ± 2.8	78.5 ± 6.7	60.8 ± 10.4
AJCC staging				<0.001
I	92.9 ± 6.9	77.4 ± 15.2	61.9 ± 18.5
II	93.5 ± 4.5	84.1 ± 9.8	—
III	90.9 ± 8.7	68.2 ± 20.7	45.5 ± 23.1
IV	75.0 ± 21.7	37.5 ± 28.6	—
Clinical T Category				0.022
cT1	92.3 ± 7.4	73.8 ± 17.5	—
cT2	91.7 ± 5.7	82.6 ± 10.1	—
cT3	—	—	—
cT4	80.0 ± 17.9	0.0 ± 0.0	—
cTX	86.0 ± 7.8	70.9 ± 11.6	35.5 ± 25.7
Thickness, mm				0.072
<2	87.5 ± 11.7	43.8 ± 31.5	—
2–8	95.8 ± 4.1	—	—
>8	94.7 ± 5.1	52.1 ± 22.6	26.1 ± 21.6
Diameter, mm				0.217
0–5	92.3 ± 7.4	82.1 ± 11.7	—
5–15	95.7 ± 4.3	79.7 ± 15.0	—
15+	80.0 ± 17.9	—	—
Sex				0.225
Male	87.5 ± 5.5	75.8 ± 9.4	—
Female	95.5 ± 3.1	82.0 ± 9.8	—

AJCC, American Joint Committee on Cancer; SE, standard error.

FIG 1.

Kaplan-Meier survival curve for all sites of uveal melanoma (UM). Cumulative survival rates for UM were 93.6% at 5 years, 80.3% at 10 years, and 63.4% at 15 years.

Discussion

To date, this is the largest study investigating the clinical features and outcomes of UM in children and adolescents. Previous studies investigating the incidence of UM in the pediatric population reported that most cases are diagnosed during the mid-to-late teenage years.^8,9 In 2013, Shields and colleagues¹⁰ reviewed 122 cases and found 3% of their cohort to be from 0–5 years of age, 11% from 5.1 to 10 years, 35% from 10.1 to 15 years, and 50% from 15.1 to 20 years. In our series of 129 cases, mean age at diagnosis was 15.9 years, with 93% of cases presenting during adolescence (≥10). Of note, we report a 100% survival rate at 15 years for patients diagnosed before 10 years of age, compared with 60.8% in those diagnosed after 10 years. Although significant, this survival estimate may not be clinically generalizable given the small sample size of patients diagnosed before 10 years of age. However, we did find age to be a significant predictor of death at last follow-up (P = 0.036). This aligns with previous findings from Al-Jamal and colleagues¹¹ in 2013 that higher mortality was associated with adolescents >17 years of age. Notably, the recent 2023 study by Masoomian and colleagues¹² reported a 2-year mortality of 9% among children aged 12 or younger, with two of the three deaths occurring in patients aged 10 years or older—consistent with our finding that mortality risk may increase with age even within the pediatric population. These findings suggest that older adolescents with UM behave clinically similarly to adults, whereas younger children may have a more favorable prognosis, although the underlying reasons remain unclear. One possible explanation for the observed survival difference is that younger patients may possess a more robust immune system, potentially enhancing their ability to combat cancer cells and prevent metastasis.¹³ Additionally, younger individuals are often able to tolerate more aggressive treatments and may have fewer comorbidities, contributing to improved outcomes.¹⁴ While our study does not include data on clinical features, staging, or genetic differences, the significant association between age and survival highlights the need for further research to determine whether early detection, biological factors, or treatment differences contribute to this trend.

Focusing on overall mortality, we reported a 5-, 10-, and 15-year cumulative survival rate estimate of 93.6%, 80.3%, and 63.4%, respectively. These estimates are more favorable than those of adults who have reported 5-, 10-, and 15- year survival rates of 79%, 66%, and 60%.¹⁵ This is in concordance with what has been previously described by Shields and colleagues¹⁶ in 2012. However, our estimates are notably lower than those presented by Singh and colleagues,⁸ who reported 5-, 10- and 15-year survival of 95%, 89%, and 77% in children and adolescents. Perhaps this is because our cohort consisted of 88% choroid/ciliary body tumors whereas Singh and colleagues⁸ included 75% from this group, with the remaining being iris melanomas. Previous studies, along with our present study, have demonstrated that melanomas arising in the choroid are more deadly than those of the iris. Compared to Singh and colleagues,⁸ our cohort had a longer median, follow-up time (74 vs 51 months) and larger number of patients (129 vs 63 patients).

Pathological differences in tumor location and staging at presentation are key prognostic indicators in adult and childhood UM. Conventionally, UM has been classified based on location (choroid, ciliary body, and iris) due to suspected differences in tumor aggressiveness.^17,18 In 1981, Barr and colleagues¹⁹ identified 5-, 10-, and 15-year mortality for iris melanoma at 8%, 8%, and 13% and for choroid/ciliary body melanoma at 21%, 21%, and 25%. Shields and colleagues^3,20 substantiate this discrepancy in mortality, as they reported the 10-year metastatic rate from iris melanoma in adults was 5 times less than ciliary body and 4 times less than choroidal. Similarly, we demonstrate a favorable prognosis of iris melanomas in children, with no deaths reported over the 16-year period among 9 cases in our series. This represents the lowest reported mortality estimate for iris melanomas in children and adolescents to date. In contrast, for choroidal melanoma, the 5-, 10-, and 15-year survival estimates were 93%, 76%, and 53%, respectively. This represents the highest reported long-term survival estimate for choroidal melanoma in children and adolescents to date.¹⁹ It has been suggested that the lower mortality rate of iris melanomas may be due to biologic activity, tumor size, and earlier diagnosis.

To better understand the relationship between tumor characteristics and UM mortality, we examined the pathological TNM staging at diagnosis for our cohort. According to the AJCC (8th edition) staging system, TNM staging is assigned based on tumor size, ciliary body involvement, and degree of extraocular extension (± 5 mm in diameter).^21,22 Those with a higher stage at diagnosis generally had worse survival rates. On analyzing for tumor size and extent of spread alone (clinical T category), we found worse long-term survival rates for T3 and T4 compared with T1 and T2. This association has been previously shown by Al-Jamal and colleagues¹¹ in their cohort of 18 northern European patients. Our findings are more generalizable because our cohort is larger and more diverse. Our results demonstrate that UM in the pediatric population appears to behave in accordance with established oncologic principles regarding the relationship between mortality and tumor stage, size, and extent of spread.

Regarding the treatment of UM in children and adolescents, those patients who received both surgery and radiation (n = 10) had the highest 15-year survival. Those who received surgery alone had higher mortality rates than those who received radiation alone. This adds to the literature a unique Kaplan-Meier estimate comparing the survival rates between treatment options for UM in the pediatric population. Our findings align with the broader oncologic literature, which indicates that combined treatment modalities often yield better survival outcomes for patients with UM, although detailed explanations of radiation and surgery types were lacking from this database study.²³

Finally, in our cohort, non-White race was a significant risk factor for death in pediatric patients with UM, suggesting that such populations may be at higher risk of mortality from this disease. Given the established rarity of melanoma in such populations, a possible contributing factor could be delayed diagnosis due to lack of adequate screening and low clinician index of suspicion. Previous studies have demonstrated that the racial disparity surrounding melanoma mortality can be attributed to social factors that lead to later stage at first presentation and delayed treatment of non-white patients.²⁴ With this in mind, clinicians should be mindful of the possibility of UM in children and adolescents with pigmented complexion.

We acknowledge some study limitations. First, the small sample sizes for iris (n = 9) and ciliary body (n = 17) melanomas compared with choroidal melanomas (n = 97) reduce the statistical power of our mortality findings, which is likely a reflection of the inherent rarity of these tumors. Second, 21 patients had incomplete data on AJCC cancer staging, thereby limiting our analysis. We also lacked detailed information on metastatic outcomes, preventing us from differentiating between deaths caused by metastasis and other causes. Regarding treatment, the NCDB database lacks adequate data about the specific type of surgery and radiation administered and does not provide reasons for why treatment was delayed in some cases. This information would help contextualize our finding that the mean time from diagnosis to treatment initiation was 27.03 days (range, 0–180). It is possible that some of these cases may have been nevi that were observed for growth and then treated due to changes, but this cannot be confirmed with available information. Lastly, the retrospective nature of our study introduces potential biases in data collection and documentation. Addressing these limitations in future research will provide a better understanding of UM in the pediatric population and improve the reliability of our findings.