Revised International Society of Paediatric Oncology (SIOP) working classification of renal tumors of childhood

The previous International Society of Paediatric Oncology (SIOP) trials and studies recognized three prognostic groups of renal tumors of childhood: low risk, intermediate risk, and high risk tumors, which were further defined in the SIOP (Stockholm) Working Classification of Renal Tumors of Childhood (1994). The results of the latest SIOP Trials and Studies showed that certain histological features which remain after preoperative chemotherapy, such as blastema, are of prognostic significance while others are not. Therefore, in the next SIOP Trials and Study a revised classification of renal tumors will be followed. It still recognizes the three tumor risk groups with different types in each of them, but for treatment purposes, only three major types of nephroblastoma need to be recognized: completely necrotic (low risk tumor), blastemal (high risk tumor), and others (intermediate risk tumors). Patients will be treated according to tumor histology and stage. Trials which include preoperative chemotherapy have shown that the presence of necrotic tumor or chemotherapy induced changes in the renal sinus or perirenal fat can be ignored for distinguishing between stage I and II, but if present at resection margins or lymph nodes, it should be regarded as stage III. Prognostic significance of all histological component of Wilms tumors will be studied prospectively in the new trial.     

Complete necrosis induced by preoperative chemotherapy in Wilms tumor as an indicator of low risk: report of the international society of paediatric oncology (SIOP) nephroblastoma trial and study 9

BACKGROUND: The SIOP Nephroblastoma therapeutic protocols include a period of preoperative chemotherapy followed by nephrectomy and a period of postoperative chemotherapy. From the outset, identification of low-risk groups has been an aim of the SIOP Nephroblastoma Trials and Studies. Now that 90% of children with Wilms tumor can be cured, attention is even more focused on the identification of patients who could benefit from less aggressive postoperative therapy, thus minimizing the morbidity and late effects associated with treatment. The prognostic implications of total necrosis in nephroblastoma after chemotherapy have not been investigated hitherto. PROCEDURE: Between November 1, 1987 and June 30, 1993, 599 patients referred to the SIOP-9 Nephroblastoma Trial and Study were preoperatively treated and classified as stages I-IV nonanaplastic Wilms tumor. RESULTS: Of these 599 patients, pathologic examination of the nephrectomy specimen revealed a completely necrotic Wilms tumor (CNWT) with no viable tumor remaining in 59 (10%): these comprised 37 stages I-III and 22 stage IV. Of these patients, 58 (98%) had no evidence of disease at 5 years vs. 90% for the rest of the cohort (P < 0.05). Stages I-III patients represented 63% of CNWT and had a 97% overall survival rate. The only death was related to veno-occlusive disease and occurred in a stage I patient in the month following nephrectomy. Stage IV patients represented 37% of CNWT (vs. only 10% of all other cases of unilateral nonanaplastic Wilms tumor) and had a 100% rate of survival. Children with CNWT were older (mean 59 months vs. 43 months); their tumor at diagnosis was larger and had regressed more significantly at subsequent ultrasound examination. The data also uphold the hypothesis that Wilms tumors of blastemic pattern are most aggressive, but also are extremely responsive to chemotherapy. CONCLUSIONS: Patients with unilateral nonanaplastic WT that showed total necrosis following preoperative chemotherapy had excellent outcome and should benefit from less aggressive postoperative treatment in further trials. Other very responsive tumors, such as Wilms with <10% viable tumor, should also be assessed.     

A 23-year experience with malignant renal tumors in infancy and childhood.

A retrospective analysis of 77 children treated between 1974 and 1996 was undertaken to evaluate morbidity and the evolution of therapy. A Wilms' tumor (WT) was present in 73 children. 74% of patients (pats.) with WT survived (54 of 73 pats.). Histological specimens of 67 patients were re-evaluated, including 4 children with non-WT histology. Among patients with Wilms' tumors (WT), nephroblastoma (NB) of intermediate risk predominated (73%; 46 of 63 pats.). Low-risk tumors occurred in 5 of 63 children (8%; mesoblastic nephroma 3, cystic partially diff. NB 1, completely necrotic NB 1). High-risk WT were diagnosed in 12 of 63 patients (19%) (NB with anaplasia 10, clear cell sarcoma 1, malignant rhabdoid tumor 1). Nephrogenic rests were present in 14 cases. We observed 3 children of school age with renal carcinoma and one patient with an intrarenal neuroblastoma. WT histology was the most important factor determining prognosis (p = 0.018). The risk for relapses was 2.6-fold higher in patients with high-risk WT compared to the standard risk group. Stages were re-evaluated according to SIOP 93-01. Comparing relapse-free survival of stages I, II and III, respectively, there was a reduced survival rate for stage III (p=0.019). According to the SIOP/GPOH protocol in 1989, the regimen was switched from primary surgery to preoperative chemotherapy without biopsy in 1989 (11 pats.). Compared to earlier years, survival improved (n.s.). In 3 patients preoperative diagnosis by means of imaging failed. During preoperative chemotherapy a venous occlusive disease of the liver occurred in 2 patients. Preoperative chemotherapy led to an impressive tumor shrinkage in the majority of patients. 2 patients of the preoperative group died (focal anaplastic NB). Long-term morbidity was analysed in 49 patients and included radiation-induced scoliosis (35), chest-wall deformity (3), congestive cardiomyopathy after relapse (1) and arterial hypertension (2). Over the years there was a trend to reduce frequency and dose of irradiation. Prognosis of WT is excellent but unfavorable histology (high risk) predicts a poor prognosis. In our experience, reduction of tumor volume due to preoperative chemotherapy facilitates tumor removal by surgery and may prevent tumor spillage and the deleterious effects of radiation in young children. Surgery without delay is necessary if the diagnosis is unclear or the tumor fails to respond to preoperative chemotherapy.     

New definitions of focal and diffuse anaplasia in Wilms tumor: the International Society of Paediatric Oncology (SIOP) experience

BACKGROUND: Unlike the original definitions of focal (FA) and diffuse anaplasia (DA) in Wilms tumor (WT), recently redefined FA and DA proved to be of prognostic significance. The aim of the study was to analyze WT from the SIOP file, the majority of which were treated with preoperative chemotherapy, in order to investigate whether chemotherapy influenced the presence of anaplasia, whether the new definitions were applicable to these tumors, and whether they were of prognostic significance. PROCEDURE: The unilateral anaplastic WT of children up to 16 years of age from the SIOP 6 and 9 nephroblastoma trials and studies were first classified according to the original definitions and analyzed. Then they were reclassified and analyzed according to the new definitions. RESULTS: Anaplasia was diagnosed in 86 (5.5%) of 1,554 unilateral WT. The age at diagnosis ranged from 9 to 175 months (median, 63) and more than half of children were over 5 years of age. From 15% to 85% of the tumor mass showed chemotherapy-induced changes. Blastemal anaplasia was seen in 74, stromal in 23, and epithelial in 22 cases. According to the original definitions, FA was diagnosed in 55 (64%) and DA in 31 (36%) cases. In total, 48% children were alive and well, including 53% with FA and 39% with DA (P = 0.23). When reclassified, 39 old FA cases were moved to the new DA group, resulting in 70 (81%) DA and 16 (19%) FA cases. The female-to-male ratio for FA changed from 1.9:1 to 1:1 while remained unchanged for DA. The percentage of FA stage I cases increased from 31% to 44%, while it decreased from 25% to 6% for stage III. For other stages it remained virtually unchanged. The overall 4-year actual survival was 75% for FA and 41% for DA (P = 0.03). CONCLUSIONS: Preoperative chemotherapy did not obliterate or produce anaplasia. The new definitions were applicable to pretreated cases and they were of prognostic significance.     

Surgical complications in the treatment of Wilms' tumor.

We present our data on the treatment of Wilms' Tumor (WT) with an emphasis on both the positive effect and the adverse effect of preoperative chemotherapy with regard to surgical intervention. From 1980 to 2000 70 children were treated. 57 % received preoperative chemotherapy (ChTx) and 43 % were operated on primarily. 75 % of the tumors responded to ChTx with significant shrinkage of the size. After preoperative ChTx 54 % of the cases were regrouped as stage I, whereas after primary operation 46 % of the patients were grouped as stage I, thus indicating a downstaging with preoperative ChTx. In 8 % of the patients with preoperative chemotherapy intraoperative complications occurred with a rupture of the tumor in 1 case. In contrast, there were intraoperative complications in 25 % of the patients with a primary operation with rupture of the tumor in 3 cases. 1 child (1.5 %) was treated with chemotherapy who did not have a Wilms' tumor but a benign nephroma (CMN). 3 cases had a clear cell sarcoma (CCSK) and in one case histology revealed a rhabdoid tumor (MRTK). In one case of CCSK only histology of the metastases disclosed the correct diagnosis. The rate of postoperative complications such as ileus was the same for both groups. Irrespective of the known adverse effects such as changing tumor histology, which may affect the correct staging, and the remaining risk of an initial inadequate treatment, our data show that the regimen of preoperative chemotherapy as proposed by the SIOP study should not be abandoned. However, the relatively small number of our patients does not allow a significant statement to be made but confirms the results of past SIOP studies.     

A Clinical Perspective of Bilateral Renal Tumors - Data from Three Consecutive German Cooperative Trials

PurposeThe therapeutic approach for bilateral renal masses is different to unilateral renal masses. This is due to biological facts such as a remarkably higher number with nephroblastomatosis, but also to the fact that clinicians must keep drug doses as low as possible to prevent side effects.Material and MethodsWe analysed the prospectively collected data of 138 patients with bilateral renal masses registered in the consecutive German national trials SIOP9/GPO, SIOP93-01/GPOH and SIOP2001/GPOH from January 1989 to May 2005.ResultsThe median follow up was 6.2 years. All but one patient already had bilateral masses at diagnosis. Median age at diagnosis was 1.9 years with a female/male distribution of 1.5/1. 18 (13%) patients had distant metastases at diagnosis. 25% of all registered patients had a concomitant syndrome. Aiming to reduce the tumor mass as much as possible, 132 patients received preoperative chemotherapy according to the trial protocols for stage V, 6 patients underwent initial surgery. Preoperative treatment duration in the nephroblastoma group ranged from 1 to 12 weeks, leading to an average volume reduction of 44%. 11 patients with bilateral nephroblastomatosis suffered from progression, 3 eventually died from nephroblastoma. 2y/5y EFS and OS for the nephroblastoma group were 82.7/71.5% and 89/85.7%, respectively. Metastases at diagnosis, local stage III and anaplasia in histology had a negative impact on outcome.ConclusionsFive treatment-associated deaths including one acute renal failure underline the importance of a cautious approach in the complex treatment of bilateral renal tumours, including nephron-sparing surgery. This aim often can be facilitated by multimodal preoperative treatment (e.g. 1, 2 or 3 four-weeks courses of actinomycin, vincristine and doxorubicin) tailored to the individual tumor status defined by imaging after each cycle.     

Pathological Evaluation of Renal Tumors in Children: International Society of Pediatric Oncology Approach

In the majority of European countries, children with renal tumors now enter the SIOP-93-01 Trial and Study. The objective of this Study is to refine methods of treatment especialy in stage I patients. The role of institutional pathologists is important in this trial. There are new criteria for stages I and II, a new SIOP Working Classification of Renal Tumors of Childhood, and morphologic and prognostic similarities of pretreated and non-pretreated anaplastic cases. Specific problems encountered in assessing tumors treated with preoperative chemotherapy, administered to the majority of children over 6 months of age entering the SIOP Study, are discussed. The identification of a new low-risk group, the completely necrotic Wilms tumor, is outlined. Received October 10, 1997; accepted October 27, 1997.     

Cavoatrial tumor extension in children with wilms tumor: a retrospective review of 17 children in a single center

The aim of this study was to evaluate the clinical characteristics and treatment results of 17 children with cavoatrial tumor extension of Wilms tumor. Of the 360 Wilms tumors diagnosed between 1980 and 2000, 17 patients with intracaval thrombus were identified from the medical records at the pediatric oncology department of Hacettepe University. The following data were collected and reviewed: age, sex, presenting symptoms, tumor site, presence of anaplasia, stage, associated congenital anomalies, localization of tumor thrombus, radiologic findings, type and duration of preoperative chemotherapy, response to preoperative chemotherapy, recurrences, and survival. The frequency of cavoatrial extension in this group was 4.7% (15 in the inferior vena cava and 2 in the right atrium). Fourteen patients received preoperative chemotherapy consisting of two-drug regimen (vincristine and actinomycin D) ranging from 1 to 12 weeks (median 4 weeks). Since intravascular invasion is often asymptomatic, a careful radiologic examination to detect tumor thrombus before surgery is essential. There is no need for aggressive surgery in the presence of tumor thrombus. It may be resolved by preoperative chemotherapy. Surgical removal of the thrombus should be considered in the presence of life-threatening tumor thrombosis at diagnosis and in patients who had residual thrombus after chemotherapy.     

Management of Wilms tumors in Drash and Frasier syndromes

Background

Children with WT1 gene‐related disorders such as Denys–Drash syndrome (DDS) and Frasier syndrome (FS) are at increased risk of Wilms tumor and end‐stage renal disease. We investigated whether Wilms tumors in these patients displayed a specific phenotype or behavior and whether nephron‐sparing surgery was beneficial.

Procedure

We retrospectively studied all patients with DDS, FS, or other WT1 mutations treated at our institutions between 1980 and 2007.

Results

We identified 20 patients, of whom 18 had benign or malignant tumors. Wilms tumors occurred in 15 patients, being unilateral in 10 and bilateral in 5 (20 tumors). Median age at Wilms tumor diagnosis was 9 months. No patients had metastases. According to the International Society of Pediatric Oncology Working Classification, there were 19 intermediate‐risk tumors and one high‐risk tumor; no tumor was anaplastic. In patients with nephropathy who underwent unilateral nephrectomy for Wilms tumor or nephron‐sparing surgery for bilateral Wilms tumor, mean time to dialysis was 11 or 9 months, respectively. Other tumors included three gonadoblastomas (in two patients), one retroperitoneal soft‐tissue tumor, and one transitional cell papilloma of the bladder. Two patients, both with stage I Wilms tumor, died from end‐stage renal disease‐related complications. The median follow‐up time for the 18 survivors was 136 months (range, 17–224 months).

Conclusion

Most Wilms tumors in children with WT1‐related disorders were early‐stage and intermediate‐risk tumors, with a young age at diagnosis. In patients without end‐stage renal disease, nephron‐sparing surgery should be considered for delaying the onset of renal failure. Pediatr Blood Cancer 2009;52:55–59. © 2008 Wiley‐Liss, Inc.     

Treatment of nephroblastoma in Africa: results of the first French African pediatric oncology group (GFAOP) study

Background

The multidisciplinary management of nephroblastoma has been defined through multicentric prospective studies and an average 90% of patients cured expected. In Africa, such studies are uncommon and results are fragmentary or unknown in most of the countries. We report the results of the GFAOPNEPHRO 01 study using SIOP 2001 protocol approach.

Procedure

From April 1, 2001 to March 31, 2004, 8 African Pilot Units were selected to participate in a nonrandomized prospective study. All patients referred with a clinical and radiological diagnosis of nephroblastoma were registered, those aged over 6 months and less than 18 years with a unilateral tumor not previously treated were included in this study and received preoperative chemotherapy. Patients with unfavorable histology or with a tumor other than Wilms tumor, and those with stage IV tumor and persistent disease after surgery were secondarily excluded.

Results

Of the 229 patients initially registered, 166 were included and finally 133 retained in the study, after surgery. Tumor rupture occurred in 7.5% of the patients. Thirty‐five percent were stage I, 22% stage II, 23% stage III, and 18% stage IV. Two‐year disease‐free survival and 5‐year survival are, respectively: 77.9% and 76.7% for localized tumors, 72.7% and 71.6% for all study patients.

Conclusions

It is possible to conduct African multicentric therapeutic studies within the framework of GFAOP. Results in terms of event‐free survival and survival are satisfactory. Improvements with respect to procedure, data collection, and outcome are expected in a new study. Pediatr Blood Cancer 2012; 58: 37–42. © 2011 Wiley Periodicals, Inc.     

Pretreatment, ultrasound-guided cutting needle biopsies in childhood renal tumors

BACKGROUND: The current International Society of Paediatric Oncology (SIOP)-10 protocol does not allow pretreatment histological classification of low-stage renal tumors in children for fear of needle tract recurrences. The aims of this retrospective study were to evaluate the safety, sensitivity, and specificity of ultrasound-guided cutting needle biopsies (UCNB) performed at our institution in pediatric patients with renal tumors. PROCEDURE: Of 28 pediatric patients presenting with a renal tumor between 1988 and 1996, 25 underwent biopsy with the Biopty biopsy instrument (needle diameter 1.2 mm). The preoperative biopsy and nephrectomy slides were reviewed by a SIOP reference pathologist. The patients' hospital records were reviewed and biopsy complications were noted. RESULTS: At review of the nephrectomy slides, the diagnoses were: Wilms tumor (16 patients), with anaplasia in one case, rhabdoid tumor (2 patients), neuroblastoma (2 patients), mesoblastic nephroma (2 patients), clear cell sarcoma (1 patient), malignant teratoma (1 patient), and renal cell carcinoma (1 patient). No needle tract recurrence or other major complication was observed. The only complication was local pain at the biopsy site, which occurred in 24% (6/25) of the cases. The sensitivity of UCNB was 76% (19/25); five biopsies did not yield diagnostic material and one was not concordant. All cases of Wilms tumor were correctly diagnosed by UCNB, but only 33% (3/9) of the other tumors. CONCLUSIONS: In all cases of Wilms tumor a correct diagnosis was made. The overall sensitivity was 76%. UCNB proved to be a safe procedure that was not associated with needle tract recurrence or other serious complications.     

CT-estimated volume of Wilms tumor can predict weight

Wilms tumor weight was used to recruit patients in a recent National Wilms Tumor Study (NWTS) group trial. The authors hypothesized that a simple calculation of tumor volume based on a preoperative CT scan could predict tumor weight. The authors reviewed charts and CT images of patients with Wilms tumors who were treated at their institution between 1985 and 2002. Tumor volume was calculated as: V = 1/6pi x d (long axis) x d (short axis) x d (craniocaudal). Weight and calculated tumor volume were correlated using linear regression. Complete data of tumor weight and volume could be determined in 25 of the 49 patients. These were highly correlated (Spearman R = 0.97). Wilms tumor weight can be predicted based on a simple estimate of tumor volume on a preoperative CT scan. CT-estimated volume may replace weight as a prognostic factor and in guiding management.     

Treatment of Wilms tumor according to SIOP 9 protocol in Casablanca, Morocco

BACKGROUND: Childhood Wilms tumor represents one of the challenge for pediatric oncologists in developing countries. We report the characteristics and treatment results of patients with Wilms tumor according to SIOP 9 protocol in Morocco. PROCEDURE: From January 1989 to December 2000, 86 children with Wilms tumor were admitted. The diagnosis was based on physical exam and abdominal ultrasound. The metastatic work-up was based on abdominal ultrasound and chest X-ray. RESULTS: The mean age was 36 months (3-120 months). The sex-ratio was 1. Abdominal mass was the main symptom at presentation (84 cases). There were 13 metastatic cases. Treatment applied was according to SIOP 9 Protocol without randomization. Local deases was present in 75 patients with stage I in 38 cases (50%), IIN0 in 4 cases (6%), IIN1 in 9 cases, and III in 24 cases (44%). The distribution of pathologic groups was: favorable in 4 cases, standard in 69 cases, and unfavorable anaplastic type in 2 cases. Sixty-nine patients were evaluable for therapeutic evaluation. Other patients were lost to follow-up. Three patients died of treatment related toxicity and 13 patients relapsed. With a median follow-up of 70 months, the 5-year EFS and 5 years overall survival for evaluable patients are 77.4% and 79%, respectively while the 5-year EFS for all patients was 56%. CONCLUSION: These results are encouraging for a developing country but special efforts should be done to reduce the rate of abandonment.     

Pediatric Renal Tumors: Practical Updates for the Pathologist

Pediatric renal tumors were targeted by the National Wilms Tumor Study Group for 4 decades with extraordinary success. Within this historic context, this review provides a summary of the new Children’s Oncology Group renal tumor protocols that will be opening in the very near future, focusing on their pathologic requirements. All renal tumors must first be registered on the Renal Tumor Classification and Banking Protocol, followed by registration on 1 of 4 primary therapeutic protocols based on histology, stage, and molecular analysis. This requires prompt submission of samples for molecular analysis and central pathologic review. Changes in staging criteria include classification of all tumor spillage as stage III, and requirement of regional lymph node evaluation for eligibility for stage I Wilms tumors (WTs) weighing less than 550 g in infants younger than 24 months and for stage I clear cell sarcoma. Patients with unilateral favorable histology WT with loss of heterozygosity for chromosomes 1p and 16q will receive more aggressive chemotherapy at each stage. Patients with bilateral WT and patients with diffuse hyperplastic perilobar nephroblastomatosis will be eligible for a novel therapeutic protocol requiring pathologic classification based on response of tumor to previous therapy. Stage I anaplastic WT will be targeted with more aggressive chemotherapy than in the past. For the first time, pediatric renal cell carcinoma will be eligible for a cooperative group protocol. All rhabdoid tumors outside the central nervous system will be eligible for a single protocol. In conclusion, these new protocols bring considerable change in their overall organization, in eligibility, and in therapy.     

基于美国儿童肿瘤学组方案治疗68例神经母细胞瘤的中长期随访结局

目的基于美国儿童肿瘤学组(COG)危险度分级的化疗方案,探讨神经母细胞瘤(NB)患儿诊断年龄与预后的相关性。方法以2007年1月至2013年3月复旦大学附属儿科医院外科诊断为NB的连续病例为研究对象,划分低危、中危和高危,分析不同INSS分期NB患儿的5年总体生存率和5年无事件生存率(EFS),并对诊断年龄和5年EFS行受试者工作特征(ROC)曲线分析,获得与EFS相关的最佳诊断年龄界值。结果 68例NB患儿进入分析,男41例(60.3%),女27例;Ⅰ期7例(10.3%),Ⅱ期14例(20.6%),Ⅲ期11例(16.2%),Ⅳ期23例(33.8%),Ⅳs期13例(19.1%)。低危24例,中危14例,高危30例。128例高危患儿术前行诱导化疗,非常好的部分缓解率为60.7%(17/28),部分缓解率为14.3%。60/68例接受手术治疗,肉眼完整切除(GTR)率为71.7%。28例失访,32例随访至5年,5年总体生存率为65.6%,其中Ⅲ期为66.7%,Ⅳ期为22.2%;5年EFS为59.4%,其中Ⅲ期为50.0%,Ⅳ期为11.1%,GTR患儿5年EFS高于未GTR患儿(70.2%vs 57.4%)。35/30例MYCN基因扩增阳性(Ⅱ期1例,Ⅳ期4例),2年总体生存率为40%(2/5),2年EFS为20%(1/5);25例MYCN基因阴性患儿,2年总体生存率为92%(23/25),2年EFS为88%(22/25)。4诊断年龄和5年EFS的ROC曲线下面积为0.713,诊断年龄2.4岁时的敏感度为75.0%,特异度为66.7%。结论采用COG治疗方案的Ⅳ期患儿的5年总体生存率为22.2%,5年EFS为11.1%。GTR与NB的预后相关,诊断年龄2.4岁可能提示预后不良。     

The prognosis of prechemotherapy blastemal predominant histology subtype in Wilms tumor: A retrospective study in China

Purpose : This study aimed to retrospectively analyze survival outcomes for Chinese patients with prechemotherapy blastemal predominant histology type Wilms tumors (WTs). Methods : We collected and analyzed clinical data concerning patients aged <15 years with favorable histology (FH) WTs treated at the Sun Yat‐Sen University Cancer Center from December 2005 to May 2016, based on the Children's Oncology Group protocol. Pathological specimens were collected through biopsy or surgical resection before initiation of chemotherapy. We analyzed survival outcomes involving different prechemotherapy histology subtypes. Results : We enrolled 97 patients with FH WTs (median follow‐up, 71.5 months; range, 22.2‐170.7). The total recurrence rate was 17.5%, and the subtype recurrence rates were as follows: blastemal predominant (45.5%), mixed (7.5%), epithelial (14.3%), and mesenchymal (9.5%) (P = .010). Five‐year event‐free survival (EFS) and overall survival (OS) rates were 84.9% and 81.4%, respectively. Respective 5‐year EFS and OS rates for subtypes were as follows: blastemal predominant (54.5% and 68.2%), mixed (90.0% and 88.9%), epithelial (85.7% and 85.1%), and mesenchymal (90.5% and 94.7%). Multivariate survival analyses showed that the blastemal predominant subtype was an independent prognostic factor of EFS (P = .001) and OS (P = .017). Conclusions : Our findings showed that prechemotherapy blastemal predominant WTs had higher recurrence and lower EFS and OS rates. Our findings suggested that, albeit with some deficiencies, blastemal predominant histology WT–diagnosed prechemotherapy may have prognostic relevance. Further research into other potential confounding variables are required to determine whether such patients warrant altered risk‐stratified therapy.     

Surgery of cavoatrial tumor thrombus in nephroblastoma: a report of the SIOP/GPOH study

BACKGROUND: Resection of a Wilms tumor extending through the inferior vena cava into the right atrium represents a challenge to the pediatric surgeon. Exact preoperative diagnosis is essential to identify the tumor and its intravascular extension. To achieve a complete excision of the tumor cardiopulmonary bypass and hypothermia may be required. The feasibility of a complete resection is important as it guides subsequent therapy such as chemotherapy and radiation. PROCEDURE: In order to define these issues, we reviewed the records of 33 of 1,151. Patients enrolled in the SIOP 93-01/GPOH Study and the SIOP 2001/GPOH Study who had a tumor thrombus into the inferior vena cava and into the right atrium. RESULTS: The median age at diagnosis was 3.73 years. Twenty-four patients had a tumor thrombus into the inferior vena cava, in nine patients the thrombus reached into the right atrium. All patients were operated on; cardiopulmonary bypass was used in nine patients. There were no deaths intraoperatively. Twenty-nine children are still alive; four patients died, one patient due to aspiration and failed resuscitation, two patients died from a recurrent tumor, and one child due to an unresectable primary tumor. CONCLUSION: Our report suggests that Wilms tumor extending to the inferior vena cava and the right atrium is technical challenging, but with adequate preoperative diagnosis and a multidisciplinary surgical approach including cardiopulmonary bypass and hypothermia, the prognosis is favorable.     

Maintenance chemotherapy to reduce the risk of a metachronous Wilms tumor in children with bilateral nephroblastomatosis

From 2009 to 2018, 10 consecutive patients with Wilms tumors and bilateral nephroblastomatosis, who had completed standard therapy, were provided a maintenance chemotherapy regimen consisting of vincristine and dactinomycin every 3 months for 12 months in order to prevent an early metachronous Wilms tumor. One patient (10%) with Beckwith‐Wiedemann syndrome developed a new tumor, without anaplasia. There were no significant toxicities reported during maintenance. All patients are currently alive with no evidence of disease. Further investigations are recommended to determine the utility of this approach.     

Imaging of pediatric renal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper focused on Wilms tumor and nephrogenic rests

Malignant renal tumors account for approximately 6% of pediatric malignancies, with Wilms tumor (WT) representing approximately 90% of pediatric renal tumors. This paper provides consensus-based imaging guidelines for the initial evaluation of a child with suspected WT and follow-up during and after therapy co-developed by the Children's Oncology Group (COG) Diagnostic Imaging and Society for Pediatric Radiology (SPR) oncology committees. The guidelines for Wilms Tumor Imaging in the Society of International Pediatric Oncology (SIOP) are briefly discussed to highlight some of the differences in imaging approach.     

Radiotherapy in the SIOP (international society of pediatric oncology) nephroblastoma studies: A review

For decades radiation has generally been accepted as a valuable supplement to surgery in the treatment of Wilms' tumor; unfortunately, it may produce undesirable late effects. It turned out, however, that when treatment is adjusted to known variables, the risk for late sequelae can be diminished in some groups of children. SIOP clinical trials have been based on children with unilateral tumors of standard histology and free of metastasis at diagnosis. The first two clinical trials, SIOP-1 (started in 1971) and SIOP-2 (started in 1974), established the beneficial effect (such as less ruptures, lower stage) of preoperative radiation and actinomycin D (AMD) in SIOP-2, with all children having radiation therapy either pre-operatively, postoperatively, or both. In the SIOP-5 trial (started in 1977), preoperative radiation therapy and AMD were compared with preoperative chemotherapy resulting in only 50% of children having radiation. The result permitted disuse of preoperative radiation in the SIOP-6 trial (started in 1980), where only one-third of the patients received postoperative radiation therapy. At present, in the SIOP-9 trial (started in 1987), fewer than 20% of children are having radiotherapy. The survival rates meanwhile have been increasing steadily from 64% in SIOP-1 to 84% in SIOP-6 for stages I, II, and III combined. © 1994 Wiley-Liss, Inc.