Japanese Journal of Clinical Oncology 30:17-20 (2000)
© 2000 Foundation for Promotion of Cancer Research
Multidisciplinary Approach to Wilms’ Tumor: 18 Years of Experience
Cerrahpasa Medical Faculty, Department of Paediatric Haematology–Oncology, University of Istanbul, Istanbul, Turkey
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: The aim was to evaluate the characteristics of Wilms’ tumor and the results of combined modality treatment obtained in our center in Turkey.
Methods: From January 1978 to December 1996, 106 patients with Wilms’ tumor were diagnosed. Of these 106 patients, 61 were male and 45 were female (M/F = 1,35); the median age at diagnosis was 39 months. The distribution of the 106 patients according to clinical stage was stage I 10%, stage II 42%, stage III 35%, stage IV 9% and stage V 4%. Histologically, 102 of the cases could be evaluated: favorable histology was diagnosed in 88.2% and unfavorable histology in 11.8% of the patients. Ninety-eight patients were treated according to NWTS and eight patients according to SIOP protocols.
Results: The EFS and overall survival rates at 2 years were 74.2 and 79.5% respectively, and at 5 years 72.4 and 76.6% respectively.
Conclusion: As a developing country we evaluated our survival rates and report an improvement in treatment in recent years.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Wilms’ tumor, the most common genitourinary malignancy of childhood, is a triphasic embryonal neoplasm consisting of varying proportions of blastema, stroma and epithelium. The tumor accounts for about 8% of childhood malignancies and so ranks fifth in incidence among the solid tumors of childhood, after central nervous system tumors, lymphoma, neuroblastoma and soft tissue sarcomas (1–3).
In past years, great progress was achieved in the treatment of Wilms’ tumor with the aid of multimodal therapy protocols (2). The goal now is to diminish late sequelae due to radiotherapy in most cases and to define risk groups to give appropriate therapy to special risk patients. In this study, the aim was to evaluate the characteristics of Wilms’ tumor and the results of combined modality treatment obtained in our centre in Istanbul, Turkey.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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From January 1978 to December 1996, 106 patients with Wilms’ tumor were admitted to the paediatric oncology unit of Cerrahpasa Medical School.
Histopathological classification and clinical staging were done according to the system of the National Wilms’ Tumor Study (NWTS) Group (4).
Clinical records were surveyed for all patients and data including age, gender, symptoms at presentation, sites of initial involvement, laboratory results, initial treatment, therapeutic response and all necessary information for life-table analysis (date of diagnosis, date of first treatment, date of relapse, date of death or last follow-up) were collected.
All the patients had complete blood counts, urine analysis and chest X-ray, hepatic and renal function tests and intravenos pyelogram (IVP). After 1987 the patients also underwent abdominal ultrosonography and computed tomography or magnetic resonance imaging as routine examination.
The histological sections were reviewed without a knowledge of outcome and other clinical details.
The majority of the patients (98) were treated with the relevant NWTS protocols and eight patients with SIOP protocols. As surgery, nephrectomy or biopsy were the main procedures. Chemotherapy treatments included actinomycin-D, vincristine and doxorubicine, cyclophosphamide for some cases. Radiotherapy was administered according to NWTS protocols, with diminishing radiation doses and field in subsequent years.
The overall survival and disease-free survival curves were plotted according to the Kaplan–Meier method.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Clinical Data
Of the 106 patients, 61 (58%) were male and 45 (42%) were female (M/F = 1.35). The median age at diagnosis was 39 months (range 2–144 months), the peak age being between 2 and 3 years of age.The age, gender and stage distribution are shown in Table 1 and the most frequent presenting findings are given in Table 2. Associated malformations were present in three patients (2.8%): macroglossia, hypospadias and aniridia. The last was a case of non-familial aniridia with 11p13 deletion. Four of the tumors were bilateral. One bilateral tumor presented with an atrial thrombus.
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Therapy
As surgical treatment, nephrectomy (50 left, 42 right) was performed in 92 patients, partial nephrectomy in four cases and only biopsy in 10 cases. Before 1990 two bilateral Wilms’ tumor cases were treated with total nephrectomy on one site and partial nephrectomy on the opposite kidney. After chemotherapy and radiotherapy, both cases were lost with renal insufficiency. Tumorectomy and partial nephrectomy were the surgical procedure since 1990; both cases have been free of tumor and renal insufficiency, for 4 and 5 years.
Toxicity
There were 19 recorded complications requiring hospitalization, in 12 children directly attributable to myelosuppression (15 episodes of febrile neutropenia and four episodes of thrombocytopenia). The majority (9; 75%) of these patients were receiving the stage IV/UH four-drug regimen. Four children who developed sepsis due to Gram-negative infection while neutropenic and three children who developed bronchopneumonia and cardiac failure were lost. Five of these patients were treated before 1987. The mortality rate due to infection and toxicity is 6.6% (7/106), while toxicity and infections account for 29% (7/24) of deaths among Wilms’ tumor patients. Five of 106 children (4.7%) developed clinically significant neuropathy due to vincristine. The children developed various forms of peripheral neuropathy. In all cases vincristine doses were delayed, decreased or both. All of the children regained their lost neurological function. Cardiotoxicity was not experienced in patients receiving adriamycin.
Histopathology
Histologically, 102 of the cases were evaluable: favorable histology was diagnosed in 90 (88.2%) and unfavorable histology in 12 patients (11.8%) (Table 1). We tried to correlate tumor DNA ploidy with outcome in 40 Wilms’ tumor cases retrospectively (5). The tumor showed heterogeneity histologically and according to DNA ploidy, but aneuploidy and tetraploidy correlated with adverse prognosis (5). The distribution of the cases with unfavorable histology were as follows: anaplasia (focal or diffuse) in 5.8%, clear cell sarcoma in 3% and rhabdoid sarcoma in 3% of the cases.
Relapse
Tumor relapse was seen in 20/99 patients (20%): two in stage I, five in stage II, seven in stage III, four in stage IV and two in stage V. Regarding histology, 15 of the patients with favorable (16.6%) and five patients with unfavorable histology (41.6%) relapsed. The most frequent site of relapse was the lung (50%) (Table 3). Three of our relapse cases who survived received the Children’s Cancer Group’s (CCG-4921) recurrent or unresponsive Wilms’ tumor treatment protocol. According to the protocol, carboplatin and etoposide were added. The EFS and overall survival rates at 2 years are 74.2 and 79.5%, respectively, and those at 5 and 10 years are 72.4, 72.4% and 76.6, 76.6%, respectively (Fig. 1). The relapse-free survival and overall survival rates according to stage and histology are presented in Table 4.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The study population was analyzed using the NWTS staging system and similar histopathological classification criteria. The incidence of Wilms’ tumor in Turkey is similar to that in others (1,2). The gender ratio (M/F) in our series was 1.35. In Turkey, Wilms’ tumor is more frequent in boys than in girls (6). In Europe the gender ratio approaches 1 while in the USA there is a female predominance (1,2). The median age of the entire patient population in our study is similar to those in other countries (6,7).
In our study, the most frequent presenting symptom was abdominal mass (95%) (Table 2). In a large series in Turkey reported by Agaoglu et al. (6), the rate of abdominal mass as a presenting symptom was given as 67%; the United Kingdom Children’s Cancer Study Group Wilms’ Tumor Trial reported this rate to be 74% (7). In our study, the reason for abdominal mass being the most frequent symptom may be explained by the advanced stages of disease of our patients at presentation.
The distribution of our patients according to clinical stages revealed that only 9% of our patients were stage I (Table 1). In the Turkish series of Agaoglu et al. (6), stage I patients were 7%. In NWTS 3, stage I patients constituted 42% of all patients (4). We may conclude that in Turkey cancer patients reach specialized centers very late for diagnosis and treatment.
In our series the associated malformation rate (2.8%) was lower than the rate of the NWTS group (7.3%) (4). This lower malformation rate may be explained by the small number of patients in the study group in comparison with the NWTS group where 3442 patients were recruited. Another point is that hemihypertrophy was the most common congenital malformation in the NWTS group (4), whereas in our series we had none. One of our patients with aniridia underwent chromosomal analysis and was revealed to have 11p13 deletion.
In our series, the localization of the tumor was the left kidney in 53% of the patients. In another large series from Turkey, the left kidney also predominated (6). Lemerle et al. (8) reported that the left kidney was involved more frequently than the right. According to Mott (9), right and left kidney involvement rates were the same.
Histopathologically, 88.2% of our patients had favorable and 11.8% had unfavorable histology. In NWTS 3 the rate of unfavorable histology was 11.12% (4), which is similar. The lungs are the most frequent (50%) organs involved as distant metastasis (1,2). The second most frequent site is the liver. Some 40% of cases with lung metastasis at diagnosis are alive, three of them free of disease and one surviving with metastasectomies.
The most frequent site of relapse was the lungs (50%) (Table 3). In the second and third NWTS, this site accounted for 58% of all relapses (10). Isolated pulmonary relapse accounted for 41% of all relapses in the first UKW study (11). In the fifth SIOP study, 54% of all relapses were isolated pulmonary events (12).
Ninety-one of our patients received NWTS 3 and NWTS 4 protocols according to years and stages. As a result, 62.6% of our patients received chemotherapy combined with radiotherapy, while 37.4% received chemotherapy alone.The distribution of our patients according to clinical stages, histological classification and survival rates can be seen in Table 4. The EFS rates at 2 years of the patients with favorable histology are 90, 83.8 and 71.4% for stages I, II and III, respectively. In NWTS 3 and UKW these rates are between 92, 87, 78% and 90, 85, 82%, respectively (4,7). In our series stage I–V and unfavorable histology the 5 year overall survival rate is 50%. In UKW the 6 year overall survival rate is 50% (7).Overall survival rates at 2, 5 and 10 years are 79.5, 76.6 and 76.6%, respectively. Event-free survival rates are 74.2, 72.4 and 72.4% 2, 5 and 10 years, respectively. The overall survival rate at 5 years was found to be 71% by Agaoglu et al. (6) in the study of 120 patients with 21 years of follow-up.
Our survival rates are lower than those of the NWTS and UKW groups. The most important cause of this difference seems to be the very low percentage of Stage I patients (9% in our patients versus 42% in NWTS 3 and 39% in UKW ), who universally have very good prognosis. When the study period was analyzed separately for 1978–87 and 1988–96, it was seen that the overall survival was 71.9 ± 6.64% for the first and 82.5 ± 6.01% for the second group. The latter value is similar to the overall survival rates reported by UKW (83%). In the literature there are only a few publications concerning the protocols and treatment results from developing countries. As a developing country we aimed to assess our adaptation to the treatment protocol and our success in treatment. The improvement in our treatment results after 1987 is probably due to the lower percentage of patients lost to follow-up, early diagnosis faciliated by ultrasonography, CT and MRI, better conditions achieved in our clinic, together with improvements in combined treatment and interdisciplinary cooperation. We believe, in fact, that the most important reason underlying all of these is the improvement in socioeconomic status.
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FOOTNOTES |
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+ For reprints and all correspondence: Alp Özkan, Suadiye Kavisli Sokak, Fidan Apt. No. 15/13, 81070 Istanbul,Turkey. E-mail: alpok @ superonline.comAbbreviations: NWTS, National Wilms’ Tumor Study; SIOP, International Society of Pediatric Oncology; UKW, United Kingdom Wilms’ Tumor Trial; EFS, event-free-survival; CT, computed tomography; MRI, magnetic resonance imaging
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REFERENCES |
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Received July 9, 1999; accepted September 30, 1999.
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