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 Table of Contents  
ORIGINAL RESEARCH REPORT
Year : 2019  |  Volume : 16  |  Issue : 2  |  Page : 68-73

Management of Wilm's tumor at the Lagos University Teaching Hospital (a 10-year retrospective study)


1 Department of Radiotherapy, Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria
2 Department of Radiation Biology, Radiotherapy, Radiodiagnosis and Radiography, College of Medicine, University of Lagos, Lagos, Nigeria
3 Department of Radiotherapy, National Hospital, Abuja, Nigeria
4 Department of Radiation Oncology, College of Medicine, University of Ibadan, Ibadan, Nigeria
5 College of Medicine, University of Lagos, Lagos, Nigeria

Date of Web Publication20-May-2019

Correspondence Address:
Dr. Anthonia C Sowunmi
Department of Radiation Biology, Radiotherapy, Radiodiagnosis and Radiography, College of Medicine, University of Lagos, Lagos
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcls.jcls_80_18

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  Abstract 


Background: Wilms' tumor (WT), also known as nephroblastoma, is the most frequently diagnosed renal tumor in children, accounting for 6% of all childhood tumors. It is relatively more common in blacks and majority of cases are diagnosed within the first 3 years of life. Aim: The study aimed to review the prevalence, pattern of presentation, and management outcome of WT at the Lagos University Teaching Hospital (LUTH). Methodology: This is a retrospective study of patients diagnosed with WT at LUTH between January 2004 and December 2013. Results: A total of 108 patients were retrieved for this study. Sixty (55.56%) patients were male and 48 (44.44%) were female with a male-to-female ratio of 1.25:1. The age range was from 9 months to 11 years with a mean age of 4 (standard deviation: ±2.37) years. The most common mode of presentation was an abdominal mass, and 66.67% of the patients presented with Stages III–V. Fifty percent of the patients had complete response following treatment (chemotherapy [CHT]) and 33 (30.6%) patients had partial response (i.e., 30% reduction in tumor size). Twenty-one (19.4%) patients had a progression of disease despite the treatment. Eleven (20.37%) had recurrence after 5 years of completing their treatment. Disease-free survival rate at 5-year posttreatment was 31.48%.
Conclusion: Most of the patients presented with advanced disease at diagnosis resulting in poor response and survival. Early presentation and diagnosis will improve the results. Combination treatment with surgery and CHT gives the best results.

Keywords: Management, nephroblastoma, pediatric cancer, Wilms' tumor


How to cite this article:
Mabadeje-Isowo AB, Sowunmi AC, Oyesegun AR, Adenipekun A, Ketiku KK, Okoro US. Management of Wilm's tumor at the Lagos University Teaching Hospital (a 10-year retrospective study). J Clin Sci 2019;16:68-73

How to cite this URL:
Mabadeje-Isowo AB, Sowunmi AC, Oyesegun AR, Adenipekun A, Ketiku KK, Okoro US. Management of Wilm's tumor at the Lagos University Teaching Hospital (a 10-year retrospective study). J Clin Sci [serial online] 2019 [cited 2019 Jun 19];16:68-73. Available from: http://www.jcsjournal.org/text.asp?2019/16/2/68/258643




  Introduction Top


Wilms' tumor (WT) (nephroblastoma) is the most common renal malignancy in children and the fifth most common childhood cancer after leukemia, central nervous system tumor, neuroblastoma, and non-Hodgkin lymphoma.[1]

It accounts for 6% of all childhood tumors with an estimated 500 new cases per year in the United States.[1] A recent study done on all children (all blacks) presenting in a tertiary institution carried out in Lagos, Nigeria, revealed, however, that black children have a 2.5 times increased incidence over their white counterparts when compared with studies done for Caucasian, and the sex ratio is approximately 1.4:1.[2] It is relatively more common in the blacks than in whites and is rare in East Asia.[3]

Estimates suggest 6–9 cases per million person-years in whites, 3–4 cases per million person-years in East Asian, and more than 10 cases per million person-years among blacks population.[3] The study of WT done in a tertiary hospital in northwestern Nigeria recorded a male-to-female ratio of 2:1.[4]

WT study done in two centers in Egypt (South Egypt Cancer Institute and Assiut University, Asyut) revealed a male–to-female ratio of 1:1 and 1:1.2, respectively.[5]

The tumor presents at an earlier age among males, with the mean age at diagnosis for those with unilateral tumors being 41.5 months and with bilateral tumor 29.5 months, compared with 46.9 and 32.6 months, respectively, among females.[6] A study done in Sokoto, northern part of Nigeria, stated that WT has the highest occurrence (48.8%) in malignant renal cancers.[7] The risk of developing WT varies among ethnic groups, with a greater risk in African Americans and a lower risk in the Asian population.[8],[9],[10] WT is primarily a sporadic disease, and only 1%–2% of individuals with WT have a relative with the disease.[11]

In some children, WT occurs as a part of a multiple malformation syndrome. The syndromes include WAGR, Denys–Drash, and Beckwith–Wiedemann syndrome.[12]

The excellent outcome now expected for most children with this tumor is attributed to the combination of effective adjuvant chemotherapy (CHT), improved surgical and anesthetic techniques, and the radio sensitivity of the tumors.[13] Survival has improved from 30% in the 1930s to over 85% currently.[13]

Current management now emphasizes reducing the morbidity of treatment for low-risk patients and reserving more intensive treatment for selected high-risk patients for whom survival remains poor.[13] The prognosis of children with WT has considerably improved from a very high mortality rate at the beginning of the 20th century to the cure rate of >90%.[14]


  Methodology Top


This was a retrospective study conducted in all patients with WT at Lagos University Teaching Hospital (LUTH) between January 2004 and December 2013.

The case files of 108 patients were reviewed from the central record, and data extracted included age, gender, presenting complaint, histological diagnosis, site of lesion, clinical stage at presentation, treatment, and response to treatment.

Data analysis was carried out using the Statistical Package for Social Sciences for Windows, Version 17.0 (SPSS Incorporation, Chicago, Ilinois, United States of America), and the results were presented using frequency tables, charts, and cross-tabulations.


  Results Top


A total of 108 patients with nephroblastoma were seen within the period of review. The patients were between the ages of 9 months and 11 years [Figure 1]. The mean age was 4 years (standard deviation: ±2.37).
Figure 1: Age of patients at presentation

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There were 60 (55.56%) male and 48 (44.44%) female with a male-to-female ratio of about 1.25:1.

The most common age group seen was within 0–2 years with a total of 45 (41.67%) patients, followed by age group of 5–6 years totaling 27 (25%) patients, age group of 3–4 years was 24 (22.22%) patients, age group of 7–8 years was 9 (8.33%) patients, age group of 11–12 years was 3 (2.78%) patients, and age group of 9–10 years was not seen at all.

WT accounts for 20.45% of all the childhood malignancies seen at LUTH between 2004 and 2013.

The most common pattern of presentation was abdominal mass only seen in 48 (44.44%) patients, followed by hematuria only in 24 (22.22%) patients, followed by abdominal mass associated with pain seen in 9 (8.33%) patients, whereas the least was abdominal mass associated with hematuria seen in 3 (2.78%) patients, and other presentations such as abdominal pain only, back pain only, cough only, and weight loss alone were seen in 6 (5.56%) patients each [Figure 2].
Figure 2: Mode of presentation

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Sixty (55.56%) patients had palpable abdominal mass on examination. Seventy-eight (72.22%) patients had palor, whereas 30 (27.78%) patients presented with weight loss. Radiological diagnosis of the primary site of malignancy in patients with WT was carried out with ultrasound scan (USS) alone in 75 patients (69.44%), with both USS and intravenous urography (IVU) in 30 (27.78%) patients and with both USS and computed tomography (CT) scan in 3 (2.78%) patients [Table 1].
Table 1: Clinical and diagnostic findings

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[Figure 3] shows the distribution of stage at presentation. Twenty-seven (25%) patients presented with Stage I disease, 9 (8.33%) presented with Stage II, 39 (36.11%) presented with Stage III, 24 (22.22%) presented with Stage IV, and 9 (8.33%) presented with Stage V.
Figure 3: Distribution of stage at presentation

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Eighty-two (75.93%) patients were histologically diagnosed as favorable and 28 (24.07%) patients had unfavorable histology.

There was no family history of WT in any of our patients.

[Table 2] shows 3 (2.78%) patients underwent surgical procedure alone, 9 (8.33%) had CHT alone, 60 (55.56%) had surgery plus CHT, and 36 (33.33%) had surgery plus CHT plus external beam radiotherapy (EBRT).
Table 2: Types of treatment modalities

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Seventy-two (72.73%) patients had radical nephrectomy, whereas 27 (27.27%) had partial nephrectomy.

Six (5.71%) patients received neoadjuvant CHT only and palliative CHT, 33 (31.43%) patients received both neoadjuvant and adjuvant CHT, and 60 (57.14%) patients received only adjuvant CHT [Table 3].
Table 3: Type of chemotherapy

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Thirty-nine (37.14%) patients in this study commenced vincristine, actinomycin D (VA), and doxorubicin regimen of CHT, followed by VA and cyclophosphamide (VAC) regimen with 30 (28.57%) patients.

Twenty-seven (25.71%) patients had VA, 30 (28.57%) had VAC, and 3 (2.86%) had VAC and doxorubicin regimens as neoadjuvant and adjuvant CHT. However, 3 (2.86%) patients had carboplatin, etoposide, and cyclophosphamide and 3 (2.86%) had cyclophosphamide, etoposide, and epirubicin regimens as palliative CHT [Table 4].
Table 4: Types of chemotherapy regimen

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Response of patients to treatment, namely CHT and radiotherapy administered to patients is shown in [Figure 4]. Fifty-four (50%) patients had complete response following treatment, 33 (30.6%) patients had partial response and required more treatment, and 21 (19.4%) patients had progression of disease despite the treatment.
Figure 4: Response to treatment

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Seventeen (31.48) patients had no recurrence, 11 (20.37%) had recurrence after 5 years of treatment, 12 (22.22%) died, whereas 14 (25.93%) were lost to follow-up [Table 5].
Table 5: Survival at 5 years

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In assessing the treatment outcome and survival rate of the patients after 5 years, only 54 (50%) cases were available for the analysis, and it revealed that 17 (31.48%) patients had no recurrence, 11 (20.37%) were alive with recurrence, 12 (22.20%) were dead, and 14 (25.93%) were lost to follow-up [Table 5].


  Discussion Top


In this retrospective study, majority of the patients studied were 2 years old, with a median age of 3 years. This is comparable with the findings of Bezuneh et al., a Tanzanian study, where the average age at presentation was 44.7 months with a median age of 36 months [15] but is not in agreement with the findings of Uba et al. who observed that the median age at diagnosis was 4 years.[16]

The ratio of male-to-female was 1.25:1 in the patients studied, which is similar to observations of Bezuneh et al., a Tanzanian study, with a male-to-female ratio of 1.4:1.[14] However, this is not in agreement with a study carried out in Jos, which showed female predominance; with a female-to-male ratio of 1.9:1.[16]

WT accounted for 20.45% of all childhood malignancies seen at LUTH between 2004 and 2013. A previous study carried at LUTH by Tijani et al. revealed that nephroblastoma constituted 24.0% of childhood tumors.[17] The difference in Lagos prevalence could be attributed to the different years that the study was conducted. Tijani et al.'s study was conducted in 1995, whereas our study was conducted in 2007; definitely newer and better methods of diagnosis have eliminated overdiagnosis, and also during our study, there were frequent strike actions by LUTH workers, and the hospital was shut down. While, the study carried out in North Central Nigeria by Uba et al. was reported in 2007, that WT constituted 43.2% of childhood cancers.[16] The variation in prevalence between the North and Lagos study can be attributed to a different geographical characteristics, patronage of the various health institutions, and level of patient inflow where these studies took place.

There was no geographical variation in this study which is similar to the one carried out in North Central Nigeria.[16]

The most common mode of presentation at diagnosis in patients studied was abdominal mass observed in 55.56%, which is similar to studies from Egypt which also reported that the most common presenting symptom at diagnosis was an abdominal mass (82%), and the study in Jos, North Central Nigeria, revealed that abdominal mass was the main symptom at presentation (100%).[18] Hematuria was the second most common presenting complaint in this study, which does not correlate with the study of Sah et al. where hematuria was the least mode of presentation.[18]

Radiological diagnosis was carried out using USS only in 69.44% of the patients studied, 27.78% in both USS and IVU, and 2.78% were diagnosed using both USS and CT scan. Recently, a study by Kim and Chung revealed that MRI is the image modality of choice to diagnose WT, as it defines the extent of intravascular involvement.[19]

Majority of patients in this study presented with Stage III (36.11%) at the time of diagnosis, which is similar to the findings observed by Sah et al. which showed that the most common stage at diagnosis was Stage III (36.5%) in Nepal.[18] The study by Uba et al. in Jos revealed that 71.9% of patients presented with Stage III–IV diseases.[16] This study does not correlate with the study by D'Angio which revealed that most patients presented with Stage I (61%).[20] This variation is due to late presentation in our patients as generally most Nigerian patients tend to present late.[16]

Histologically, 75.93% of the patients in this study had favorable histology, whereas 24.07% had unfavorable histology, which is similar to the observations made by Bezuneh et al. in Tanzania which revealed favorable histology in 89.7% and unfavorable histology in 10.3% of patients.[15]

Treatment modalities for patients with WT include surgery, CHT, and EBRT. This is comparable with the findings among the patients studied in this research work because 91.67% of the patients had surgical procedures (either as radical or partial nephrectomy), 105 (97.22%) had CHT (either as neoadjuvant or adjuvant or palliative CHT), and 36 (33.33%) had EBRT.

Surgical procedures carried out in this study were radical nephrectomy and partial nephrectomy which accounted for 72.73% and 27.27%, respectively. Partial nephrectomy was carried out among the patients with Stage III-V diseases in this study because they presented with advanced diseases. However, a report from the literature recommended that partial nephrectomy should be performed at Stage V disease and solitary kidney, or rare cases of horseshoe kidney.[21],[22]

Neoadjuvant CHT was recommended in patients studied to downstage tumors, making it operable. Thirty patients had neoadjuvant CHT which showed a significant reduction in tumor size in few patients. However, 69 patients had adjuvant CHT and 6 patients had palliative CHT, patients who presented with Stage IV disease.

Curative intent radiotherapy dose of 30–40 Gy in 20–26 fractions over 4–41/2 weeks is usually given using linear accelerator (LINAC) machine.

One-third of the patients had radical radiotherapy as adjuvant treatment due to the fact that they did not complete their treatments or the radiotherapy machine (LINAC) was faulty or they were lost to follow-up. Furthermore, patients with Stage I–IV diseases had postoperative EBRT due to the aggressiveness of tumor histology and tumor spillage at surgery. This is comparable with observation from the literature which revealed that postoperative radiation therapy to the tumor bed is required when a biopsy is performed or in the setting of local tumor Stage III.[23],[24],[25],[26]

Fifty-four (50%) patients attained complete response (i.e., all detectable tumor have disappeared), 33 (30.6%) had partial response (i.e., reduction of tumor size by at least 30% in the widest dimension), whereas 21 (19.4%) had no response in the patients studied. Mortality rates for WT have decreased in most of the developed countries in the past few years, and this is most probably due to improvements in the treatment. About 15.74% of the patients had no recurrence which is lower than the findings by Sah et al. conducted in Nepal [18] and Peciulyte et al. in Lithuania [27] (50% and 73%, respectively). This could be due to the fact that supportive care was better in Nepal, as the most common stage at diagnosis was Stage III.

The relapse rate in patients studied was 20.37% which was higher than the findings of Sah et al. (17%). The mortality rate (22.22%) was higher in this study, which is comparable with observations of Sah et al. where death rate was 20%.[18] About 25.93% were lost to follow-up visits in this study, which differs from the report by Sah et al. where 13% of patients were lost to follow–up,[18] and this could be because of low socioeconomic condition and low awareness about the condition. This study also differs from that conducted in Nepal, South Central Asia, by Peciulyte et al. where no one was lost to follow-up.[27]

Survival at 5 years revealed overall disease-free survival of 31.48%. About 20.37% of the patients studied developed recurrence, whereas 22.22% of the patients were dead and 25.93% were lost to follow-up. The outcome of our patients was poor due to late presentation with advanced disease, lack of multidisciplinary treatment, occasional radiotherapy machine breakdown, defaults, and frequent interruptions of treatment with poor compliance. It is comparable with the observation of Uba et al. from Jos in Nigeria where 43.8% of patients studied were alive between 1 and 9 months of follow-up period, but there was no survivor at 2 years after treatment. Their outcome was poor because they lack radiotherapy services, poor availability of cytotoxic drugs, and inadequate follow-up in their center.[16]

However, it is different from the observation from both the National Wilms Tumor Study/Children's Oncology Group and International Society of Paediatric Oncology groups where the overall 5-year survival rates for WT was 90%.[28],[29],[30]


  Conclusion Top


Global cancer scourge and burden is not only limited to adults but to children as well. This study revealed that the most common age groups were from 0 to 6 years, and most of the patients presented with advanced disease at diagnosis resulting in poor treatment response and survival outcome. Thus, the need for massive nationwide education and advocacy to the populace that the key to cure is early presentation. Stage disease can be cured when patients present early.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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