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DOI: 10.2174/0250688203666210111153116, 2021, 2(1), 84-90

New Emirates Medical JournalContent list available at: https://newemiratesmedicaljournal.com

RESEARCH ARTICLE

The Clinical Characteristics and Survival Profiles of Wilms Tumor in the UnitedArab Emirates: A Single-center Retrospective Analysis

Abdulrahman Mohammad AlJassmi1,*, Asim Noor Rana1, Hani Humad1 and Anjan Madasu1

1Department of Pediatric Hematology and Oncology, Dubai Hospital, Dubai, United Arab Emirates

Abstract:

Background:

Wilms Tumor (WT) is the most common pediatric kidney tumor, yet the disease has variable clinical characteristics and prognostic outcomesacross different populations.

Objective:

This study aims to review the clinical characteristics and survival outcomes of children with WT who have received treatment at Dubai Hospital,UAE.

Methods:

A retrospective study was conducted involving the medical records of confirmed WT children (aged < 14 years) who had received treatmentbetween 2013 and 2018. Diagnosis should have been established based on the histopathological examination of operable tumors and needle biopsyfor inoperable tumors. The Société Internationale d’Oncologie Pédiatrique (SIOP) WT 2001 protocol was used for patient management, and theUMBRELLA SIOP–RTSG 2016 Wilms tumor pathology and molecular biology protocol was used for histopathologic classification and clinicalstaging. The presenting sign and symptoms, the findings of diagnostic imaging techniques, histological grading, the received treatments, andfollow-up outcomes were collected and analyzed. Kaplan-Meier survival analysis was used to carry out the survival analysis.

Results:

Ten children were diagnosed with WT (median age of 3.40 years, 60% males). All patients presented with abdominal masses without prominentpain. Synchronous bilateral lesions were found at diagnosis in one patient and metastatic lesions in three patients. Four children were dischargedagainst medical advice; five received treatment according to the SIOP WT 2001 regimen, while the remaining patient was managed in the UnitedStates according to the National Wilms Tumor Study Group (NWTSG) protocol. The overall 6-year and relapse-free survival rates were 90% and80%, respectively.

Conclusion:

The clinical characteristics and managemental outcomes of children presenting with WT are promising, possibly owing to adopting the SIOPprotocol. Considering the small sample size, more large-scale, nation-wide studies are warranted.

Keywords: Wilms tumor, Kidney neoplasms, Chemotherapy, Hereditary, Survival, United Arab Emirates.

Article History Received: May 30, 2020 Revised: November 20, 2020 Accepted: December 01, 2020

1. INTRODUCTION

Wilms Tumor (WT), or nephroblastoma, is a form ofkidney cancer that is typically reported in children aged lessthan five years. It was first described in 1814, yet its neoplasticnature and the pluripotent cellular content were first identifiedin 1899 by the German physician Max Wilms [1]. According to

* Address correspondence to this author at the Department of PediatricHematology and Oncology, Dubai Hospital, Dubai, United Arab Emirates;Tel: +971506511190; E-mail: amaljassmi@dha.gov.ae

the American Cancer Society [2], WT ranks fifth among allcancers affecting children and adolescents, with an estimatedincidence of 8.3 per million population during the period2011-2015 (500-600 new cases each year). The affectedchildren usually present with asymptomatic abdominal masses,which could be discovered by the mother during bathing.Abdominal pain is another common symptom (in approxi-mately 30% to 40% of patients. Other symptoms includevaricocele, fever, anemia, urinary tract infections, and eithermicroscopic or macroscopic hematuria [3]. In addition,

A Single-center Retrospective Analysis 85

hypertension may occur due to increased renin activity (withthe presence of a renal mass). Patients may rarely present withhepatomegaly, ascites, and congestive cardiac failure; suchsymptoms result from vascular extension (the inferior venacava or renal vein) or compression of surrounding organs [4].Occasionally, tumor rupture would be associated with a rapidlyenlarging abdominal mass and acute pain.

Clinical evaluation of WT patients relies heavily onimaging studies, such as ultrasonography (US), computedtomography (CT) and magnetic resonance imaging (MRI),which would help in subsequent therapeutic planning anddetecting the potential metastatic sites [5]. WT managemententails a multidisciplinary approach by pediatric oncologists,radiologists, and radiation oncologists to improve survivaloutcomes. Actually, the overall survival following WTdiagnosis has improved from 20% in the 1960s to 92% and78% in developed and developing countries, respectively [6,7]. Indeed, these rates have been attained owing to thesignificant multidisciplinary collaboration of SociétéInternationale d’Oncologie Pédiatrique (SIOP) and theNational Wilms Tumor Study Group (NWTSG) [8]. However,multiple factors could influence patients’ survival acrossdifferent countries, such as the limited access to healthcareresources, shortage of professional personnel, poorinfrastructure, and distance to specialized treatment centers.These factors would lead to late presentation and contribute tolow survival rates [9]. Other factors associated with diminishedsurvival rates include metastatic disease at presentation,intraabdominal recurrence, and anaplasia [10].

Therefore, it is crucial to identify the current clinical statusof WT patients, including the clinical presentation and thediagnostic approaches. Moreover, it is necessary to assess theoutcomes of the used therapeutic regimens in terms of survivaloutcomes. However, as with other members of the GulfCooperation Council, the United Arab Emirates (UAE) has norecent publications concerned with investigating WT featuresand outcomes. Based on the Human Development Reports ofthe United Nations’ Development Program [11], UAE has beenrecently considered a developed nation (with a humandevelopment index > 8) with a fast-growing economy andmodern healthcare infrastructure. However, only tworetrospective analyses were conducted about WT locally, andboth are outdated [12, 13]. Therefore, the present study wasconducted to review the pathological and clinical patterns aswell as surgical outcomes and prognosis in children with WTpresenting to a multispecialty hospital in UAE.

2. MATERIALS AND METHODS

A retrospective study was conducted involving the medicalrecords of children diagnosed with WT at the Department ofPediatric Hematology and Oncology, Dubai Hospital, UAE,during the period between January 2013 and December 2018.Dubai Hospital is a specialized medical institution that receivesabout 250 000 patients per year, with a highly specializedpediatric care center. Verbal consent was obtained from theparents of all included children. Ethical approval was obtainedfrom the institutional review board of Dubai Hospital(Reference number: DSREC-04/2018_12).

The included patients were children (aged <14 years)diagnosed with Wilms tumor based on the results of thepathological examination of lesions (for operable tumors) orneedle biopsy (for inoperable tumors). Patients with incompleteclinical data were excluded. Eligible patients were managedaccording to the SIOP WT 2001 protocol [14], which includesan upfront chemotherapy regimen, followed by surgery andpathological examination. In children aged >6 months, post-chemotherapeutic nephrectomy was planned on week five forpatients with localized tumors and on week seven formetastatic tumors. Younger children were referred to pediatricsurgeons to perform an upfront nephrectomy. Postoperativechemotherapy and/or radiotherapy were given based on thestage and risk stratification of the protocol. Histopathologicclassification and clinical staging of the lesions were based onthe UMBRELLA SIOP–RTSG 2016 Wilms tumour pathologyand molecular biology protocol [15].

Clinical data were collected from medical records,pathology and imaging records. Data in outpatient records wereused to obtain follow-up information. The collected dataincluded: 1) demographic data: age at diagnosis, gender, and ahistory of other anomalies; 2) the presenting signs andsymptoms, such as abdominal pain, fever, hematuria, etc.; 3)imaging-related data, including the results of US, computedtomography CT, and chest X-ray (CXR), stage at presentation,the affected kidney (s), tumor dimensions, and metastasis; 4) management-related data, including undergoing surgery,preoperative chemotherapy; 5) histological grade; 6) follow-updata, such as follow-up time and the response to treatment.

Statistical analysis was carried out using the StatisticalPackage for Social Sciences version 19.0 (SPSS Inc., Chicago,IL, USA). Categorical variables were presented as frequencyand percentage, while quantitative variables were presented asmean ± standard deviation (SD) or median and ranged asappropriate. Normality of data distribution was assessed usinga Kolmogorov-Smirnov test and a Shapiro-Wilk test, wherenormally-distributed data was considered at P>0.05. Tumorvolume was calculated based on the ellipsoid formula:

, where D, L, and W are the tumor radiusin the three dimensions [16]. The mean duration of overallsurvival (OS) and disease-free survival (DFS), as well as theirrespective 95% confidence interval (CI), were estimated usingKaplan-Meier survival analysis and compared using a log-ranktest. The comparative analysis was based on the followingvariables: age (<5 or ≥5 years), gender, tumor stage atpresentation (localized or disseminated), lesion status (solitaryor multiple), abdominal lymph node metastasis (LNM), distantmetastasis (DM), and response to treatment. Statisticalsignificance was considered at P < 0.05.

3. RESULTS

A total of ten children were diagnosed with WT, with amedian age of 3.40 years (0.6-9.5) and a sex ratio (M/F) of1.5:1. No other associated anomalies were reported in allpatients. The mean tumor volume was 572 cm3 (119-2136).Lesions were most common in the left kidney (60%), while onechild presented with lesions in both kidneys (Table 1).

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Table 1. Demographic and clinic-pathological data of children with WT (n=10).

Parameter Category Frequency %

Age<5 years 7 70.0>5 years 3 30.0

GenderMale 6 60.0

Female 4 40.0

The affected kidneyLeft 6 60.0

Right 3 30.0Bilateral 1 10.0

Stage at presentation

I 2 20.0II 3 30.0III 1 10.0IV 3 30.0V 1 10.0

Number of lesionsSingle 7 70.0

Multiple 3 30.0

Metastasis at presentationNone 6 60.0

Lymph nodes 1 10.0Lungs 3 30.0

Response to treatmentComplete response 5 50.0Metastatic relapse 1 10.0

DAMA 4 40.0DAMA: Discharge Against Medical Advice.

Diagnostic data was primarily based on clinical andimaging findings. While an abdominal mass was a predominantclinical feature in all cases, none of them experienced signs ofabdominal pain. Besides, fever, weight loss, and hematuriawere present in 4, 2, and one patient, respectively. Notably,hypertension was not apparent in any case.

Abdominal US was performed and coupled to CXR in allpatients. Nine patients (90%) underwent CT scans. Threepatients had multiple lesions; the left kidney was involved intwo patients and bilateral lesions were found in the third child.The tumors extended to the renal cortex in three patients and tothe renal pelvis and major calyces in one patient. Cystic areaswere observed in three patients. No calcification or vascularinvolvement was visualized. One child with a single largelesion developed hydronephrosis. The tumors displacedcontralateral structures in two patients; bowel loops only in onepatient and bowel loops, the aorta, the pancreas, and the portalvein in one child.

Four patients had disseminated lesions (three children withdistant metastasis and one patient with bilateral renal lesions);and the remainders had localized lesions (stage I-III, Table 1).A distant focal lesion in one lung, as well as distant foci in theaxillary and paraaortic lymph nodes, was observed in onechild, whereas two children had multiple bilateral lung nodules.Metastasis to regional lymph nodes (anterior retroperitonealregion) was revealed by radiography in one child.

Unfortunately, four patients were discharged against

medical advice (DAMA) and thus were deemed lost to follow-up. One of these patients returned back 18 months afterdiagnosis (parental delay) with metastasis and bilateral lesions,and he finally died.

Of the remaining six patients, five children receivedpreoperative chemotherapy followed by surgery according tothe SIOP WT 2001 protocol [14]. One child traveled to theUnited States and received treatment according to the NWTSGprotocol [17]. Hence, the histological grading was available forfive patients (intermediate risk in four children and low risk inone child). The surgical intervention consisted of radicalnephrectomy in all patients.

The mean follow-up period was 45.6 ± 34.39 months. Allpatients, including the NWTSG-receiving child, completedtheir therapies and showed a good response to treatment.However, the child who had presented with a solitarymetastatic lesion developed a metastatic pulmonary relapse twoyears after surgery. The mean duration of overall survival was64.29 months (95% CI, 50.29 to 78.28) and DFS was 57.43months (95% CI, 40.32 to 74.54, Fig. 1). Survival analysisincluded all patients who had entered the study, since theexclusion of those who lost-to-follow-up may induce aselection bias [18]. Therefore, patients with incomplete datawere judged as “censored”, and the last known date of theirobservation was included in the analysis [18]. At the univariateanalysis, the durations of OS and DFS have not beeninfluenced by any of the variables incorporated into the model.The six-year OS and DFS were 90% and 80%, respectively.

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A Single-center Retrospective Analysis 87

Fig. (1). Survival curves depicting the overall survival (A) and disease-free survival (B) of children under study.

4. DISCUSSION

WT is the most common form of kidney cancer inchildhood. In the most recent report of the National CancerRegistry in 2015 [19], cancers of the kidney and renal pelvisrepresented about 6.1% of all cancers among pediatric patientsin UAE. However, little is known about the local clinical andepidemiological patterns of WT. In the present descriptivestudy, we reviewed the clinical findings in a small sample ofchildren who had presented to our hospital during the study

period. There was a predominance of abdominal masses atpresentation. In a 20-year experience in Hong Kong, Chan etal. [20], revealed that the most frequent symptom was anabdominal mass with or without abdominal distension and pain(75% of patients). Similar outcomes were noted in the study ofthe United Kingdom Children's Cancer Study Group [21].Moreover, in the present analysis, the median age at diagnosiswas 3.4 years (40.8 months). Other investigations in Turkey,Eastern China, Jordan, and Egypt [22 - 25] as well as the earlystudy conducted in UAE [12] showed similar age ranges.

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Nonetheless, Al Mulhim [26] found a lower median age (2.5years) in a ten-year experience in Khobar, Saudi Arabia. Ingeneral, as with other reports, most children presenting withWT are less than 5 years. Besides, the presence of anabdominal mass on examination was the most predominantsymptom.

Chemotherapy has proven effective in WT since itcontributes to debulking and downstaging the tumors.Moreover, chemotherapeutic regimens may lead to a totaldisappearance of lesions at least on one side in patients withbilateral tumors [13]. These regimens are included in bothstandard treatments of the SIOP and NWTSG groups.However, the SIOP approach entails preoperative neoadjuvantchemotherapy, while postoperative regimens depend on thestage of the disease. The NWTSG approach includesimmediate surgery with postoperative chemotherapy as app-ropriate. Indeed, both approaches have achieved comparablesurvival rates. While early 5-year survival rates rangedbetween 73% and 91% during the period between 1988 and1997 [27], current rates reached as high as 92% in developedcountries [28 - 30]. In developing countries, these figures stilllag behind those of developed countries. For instance, in India,the OS improved from 55% to 80% in 1985-1995 and2004-2014, respectively [31, 32].

In a large epidemiological analysis of WT children inEuropean countries, Doganis et al. [29], found that complianceto standard treatment is an essential factor in raising survivalrates. Evidently, in the present study, delayed treatment in apatient diagnosed at one year of age led to the development ofa metastatic phenotype as well as a metachronous disease (thecontralateral kidney was subsequently affected) and finallydeath after 1.5 years of diagnosis. This underscores theimportance of rapid intervention as appropriate. Other potentialcauses of low survival rates in other settings include delays inthe application of recent treatment advances, use of modifiedprotocols, variable adherence to guidelines, lack of resources,or lack of trained multidisciplinary teams [33 - 36].

In the present analysis, relapse occurred in one patient withan advanced anatomical grade (grade V). It has been well-established that patients with advanced disease and/or high-riskhistology are more likely to experience poor clinical outcomesand short survival [30]. Although the survival rate in thecurrent study approximates that of other developed countries,four patients (40%) were lost to follow-up and the correlationbetween their clinical characteristics and treatment outcomeswas not investigated. A patient with bilateral lesions hasDAMA and his clinical and prognostic outcomes might affectthe reported results in the current analysis.

There were no significant risk factors of poor survival inthe present study. The lack of statistical significance isattributable to the small sample size and the high frequency ofpatients lost during follow-up. Additionally, the retrospectivedesign of the study based on the medical records did not allowus to detect causal relationships between several clinical factorsand outcomes measures. Supposedly, conducting futureprospective studies of children diagnosed with WT wouldreveal additional covariates that might affect the response totreatment and survival profiles.

CONCLUSION

Children with WT presented with a median age of 3.4years with a predominance of abdominal masses at presen-tation. The percentage of patients with synchronous bilaterallesions and metastatic phenotypes was 10%. The use ofevidence-based protocols, such as the SIOP WT 2001 regimen,has been associated with revolutionary changes in the clinicalburden and survival patterns. The OS rate in the current studywas 90%, reflecting institutional compliance to themanagemental guidelines implied by the SIOP as well asconducting efficient multidisciplinary treatments. However,intensifying medical care to children with advanced anatomicalstaging, bilateral lesions, and metastatic tumors should beemphasized. Considering the experienced limitations,nationwide studies are recommended to investigate theepidemiological profiles of such a common renal tumor on alarge scale.

LIST OF ABBREVIATIONS

CI = Confidence Interval

CT = Computed Tomography

CXR = Chest X-ray

DAMA = Discharged Against Medical Advice

DFS = Disease-free Survival

DM = Distant Metastasis

LNM = Lymph Node Metastasis

MRI = Magnetic Resonance Imaging

NWTSG = The National Wilms Tumor Study Group

OS = Overall Survival

SD = Standard Deviation

SIOP = Société Internationale d’Oncologie Pédiatrique

UAE = United Arab Emirates

US = Ultrasonography

WT = Wilms Tumor

ETHICS APPROVAL AND CONSENT TO PARTI-CIPATE

The ethical approval of the study was obtained from theIRB of Dubai Hospital (Reference number:DSREC-10/2020_28).

HUMAN AND ANIMAL RIGHTS

Not applicable.

CONSENT FOR PUBLICATION

Verbal consent was obtained from the parents of includedchildren.

AVAILABILITY OF DATA AND MATERIALS

The data supporting the findings of the article is availablein the zenodo.org repository at: https://doi.org/10.5281/zenodo.4051125, reference number 4051125.

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FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial orotherwise.

ACKNOWLEDGEMENTS

Declared none.

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