Role of ultrasonography (USG) and color Doppler in the evaluation of thyroid nodules and its association with USG-guided FNAC - A cross-sectional study.

Introduction: Thyroid diseases affect approximately 42 million people in India. The majority (15%-40%) of these cases remain asymptomatic and benign and warrant special investigations such as ultrasonography (USG) and fine-needle aspiration cytology (FNAC) for diagnosis. Early diagnosis and management of thyroid disorders determine the disease course in many patients. Objective: To determine the role of USG and color Doppler in the evaluation of thyroid nodules and its association with USG-guided FNAC. Methods: We did a cross-sectional analytical study over 2 years, where we recruited 108 patients with thyroid swelling attending the OPD. We used a semi-structured data collection proforma that captured information on sociodemographic details, clinical symptoms, physical examination, and all ne cessary laboratory investigations. All patients underwent USG, color Doppler, and FNAC as a part of the investigation of thyroid nodules. The diagnostic value of ultrasound and Doppler parameters was assessed in terms of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for detection of malignancy in comparison to FNAC. Results: Approximately 155 nodules were identified from the selected 108 cases, and the prevalence of malignancy among the selected thyroid nodule patients was found to be 9.1%. We observed that malignant tumors were likely to be solitary with lobulated margins, >2 cm in size with <50% peripheral halo, with markedly hypoechoic, predominantly solid, with nodal involvement and extrathyroidal extension, microcalcifications, and central vascularity. We also observed that tumors that had USG characteristics of being taller than wide (91%), poorly defined margins (92%), marked hypoechoic (95%), and microcalcifications (96%) had the highest diagnostic accuracy in detecting malignancy when compared to FNAC. Conclusion: Thus, through our study findings, we conclude that USG and color Doppler can serve as vital tools for the evaluation of thyroid nodules with high sensitivity and specificity.

Unusual imaging findings associated with abdominal pediatric germ cell tumors.

Germ cell tumors of childhood are tumors arising from germline cells in gonadal or extragonadal locations. Extragonadal germ cell tumors are characteristically located in the midline, arising intracranially or in the mediastinum, retroperitoneum, or pelvis. These tumors are generally easily diagnosed due to typical sites of origin, characteristic imaging findings, and laboratory markers. However, germ cell tumors can be associated with unusual clinical syndromes or imaging features that can perplex the radiologist. This review will illustrate atypical imaging/clinical manifestations and complications of abdominal germ cell tumors in childhood. These features include unusual primary tumors such as multifocal primaries; local complications such as ovarian torsion or ruptured dermoid; atypical presentations of metastatic disease associated with burned-out primary tumor, growing teratoma syndrome, and gliomatosis peritonei; endocrine manifestations such as precocious puberty and hyperthyroidism; and antibody mediated paraneoplastic syndrome such as anti-N-methyl-D-aspartate-receptor antibody-mediated encephalitis. This review aims to illustrate unusual imaging features associated with the primary tumor, metastatic disease, or distant complications of abdominal germ cell tumors of childhood.

Treatment and outcomes of clear cell sarcoma of the kidney: A report from the Children's Oncology Group studies AREN0321 and AREN03B2.

BACKGROUND: On the fifth National Wilms Tumor Study, treatment for clear cell sarcoma of the kidney (CCSK) included combined vincristine, doxorubicin, cyclophosphamide, and etoposide (regimen I) plus radiation therapy (RT), yielding 5-year event-free survival (EFS) rates of 100%, 88%, 73%, and 29% for patients who had with stage I, II, III, and IV disease, respectively. In the Children's Oncology Group study AREN0321 of risk-adapted therapy, RT was omitted for stage I disease if lymph nodes were sampled, and carboplatin was added for stage IV disease (regimen UH-1). Patients who had stage II/III disease received regimen I with RT. METHODS: Four-year EFS was analyzed for patients enrolled on AREN0321 and on those enrolled on AREN03B2 who received AREN0321 stage-appropriate chemotherapy. RESULTS: Eighty-two patients with CCSK enrolled on AREN0321, 50 enrolled on AREN03B2 only. The 4-year EFS rate was 82.7% (95% confidence interval [CI], 74.8%-91.4%) for AREN0321 and 89.6% (95% CI, 81.3%-98.7%) for AREN03B2 only (p = .28). When combining studies, the 4-year EFS rates for patients who had stage I (n = 10), II (n = 47), III (n = 65), and IV (n = 10) disease were 90% (95% CI, 73.2%-100.0%), 93.4% (95% CI, 86.4%-100.0%), 82.8% (95% CI, 74.1%-92.6%), and 58.3% (95% CI, 34%-100.0%), respectively. There were no local recurrences among seven patients with stage I disease who were treated without RT. One stage I recurrence occurred in the brain, which was the most common site of relapse overall. Among patients with local stage III tumors, neither initial procedure type, margin status, nor lymph node involvement were prognostic. CONCLUSIONS: Patients with stage I CCSK had excellent outcomes without local recurrences when treated without RT. Patients with stage IV disease appeared to benefit from a carboplatin-containing regimen, although their outcomes remained unsatisfactory. Further research is needed to improve outcomes for patients with advanced-stage disease (ClinicalTrials.gov identifiers NCT00335556 and NCT00898365).

Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: A report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5.

BACKGROUND: Patients with stage IV favorable histology Wilms tumor (FHWT) with extrapulmonary metastases (EPM) constitute a small subset of patients with FHWT. Because of their rarity and heterogeneity, optimal FHWT treatment is not well understood. Children's Oncology Group protocol AREN0533 assigned patients with FHWT and EPM to intensified chemotherapy, regimen M, after initial DD-4A chemotherapy. To improve understanding of prognostic factors and best therapies, experiences of patients with EPM on AREN0533, as well as on protocols AREN03B2 and NWTS-5, were reviewed. METHODS: Combined outcomes for patients with EPM from NWTS-5, AREN0533, and AREN03B2 were determined. Those treated on AREN0533 were compared with those treated on NWTS-5. Prognostic factors were explored in the pooled cohort. RESULTS: Forty-seven patients with FHWT with EPM enrolled on AREN0533, 37 enrolled on NWTS-5, and 64 were followed only on AREN03B2. The pooled cohort of all 148 patients demonstrated a 4-year event-free survival (EFS) of 77.3% (95% CI, 70.8-84.4) and 4-year overall survival of 88.9% (95% CI, 83.9-94.2). Four-year EFS of patients with EPM treated on AREN0533 was 76.0% (95% CI, 64.6-89.4) vs 64.9% (95% CI, 51.7-82.2) on NWTS-5; hazard ratio, 0.64, p = .26; no difference in overall survival was observed. Increasing linear age and slow incomplete lung response were associated with worse EFS in a pooled cohort. CONCLUSIONS: Outcomes for patients with EPM are among the lowest for children with FHWT. Further trials with standardized surgical and radiation treatment to metastatic sites, and prospectively collected biologic and treatment details are needed. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov identifiers: NCT00379340, NCT00898365, and NCT00002611.

Cancer Therapy-related Hepatic Injury in Children: Imaging Review from the Pediatric LI-RADS Working Group.

The liver is the primary organ for the metabolism of many chemotherapeutic agents. Treatment-induced liver injury is common in children undergoing cancer therapy. Hepatic injury occurs due to various mechanisms, including biochemical cytotoxicity, hepatic vascular injury, radiation-induced cytotoxicity, and direct hepatic injury through minimally invasive and invasive surgical treatments. Treatment-induced liver injury can be seen contemporaneous with therapy and months to years after therapy is complete. Patients can develop a combination of hepatic injuries manifesting during and after treatment. Acute toxic effects of cancer therapy in children include hepatitis, steatosis, steatohepatitis, cholestasis, hemosiderosis, and vascular injury. Longer-term effects of cancer therapy include hepatic fibrosis, chronic liver failure, and development of focal liver lesions. Quantitative imaging techniques can provide useful metrics for disease diagnosis and monitoring, especially in treatment-related diffuse liver injury such as hepatic steatosis and steatohepatitis, hepatic iron deposition, and hepatic fibrosis. Focal liver lesions, including those developing as a result of treatment-related vascular injury such as focal nodular hyperplasia-like lesions and hepatic perfusion anomalies, as well as hepatic infections occurring as a consequence of immune suppression, can be anxiety provoking and confused with recurrent malignancy or hepatic metastases, although there often are imaging features that help elucidate the correct diagnosis. Radiologic evaluation, in conjunction with clinical and biochemical screening, is integral to diagnosing and monitoring hepatic complications of cancer therapy in pediatric patients during therapy and after therapy completion for long-term surveillance. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material See the invited commentary by Ferraciolli and Gee in this issue.

Similarities and controversies in imaging of pediatric renal tumors: A SIOP-RTSG and COG collaboration.

Malignant renal tumors are rare in children, and Wilms tumors (WTs) are the most common subtype. Imaging plays an essential role in the diagnosis, staging, and follow-up of these patients. Initial workup for staging is mainly performed by cross-sectional imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Imaging approach within the two core international groups, the Children's Oncology Group (COG, North America) and the International Society of Pediatric Oncology - Renal Tumor Study Group (SIOP-RTSG, Europe), differs. Whereas abdominal ultrasound (US) is used for the initial diagnosis of a suspected pediatric renal tumor globally, COG protocols support the use of CT or MRI for locoregional staging, contrary to the preference for MRI over CT for abdominopelvic evaluation within the SIOP-RTSG. The purpose of this manuscript is to summarize current imaging approaches, highlighting differences and similarities within these core international groups, while focusing on future innovative efforts and collaboration within the HARMONICA initiative.

Optimizing Imaging of Pediatric Liver Lesions: Guidelines from the Pediatric LI-RADS Working Group.

A differential diagnosis based on a patient's age, clinical presentation, and serum α-fetoprotein level will help guide the initial imaging workup in children with a liver lesion. Children vary significantly in size, the ability to stay still, and the ability to breath hold for imaging examinations. Choosing and tailoring imaging techniques and protocols for each indication and age group is important for optimal care with minimal invasiveness. The need for sedation or anesthesia can be obviated by using techniques like feed and bundle, distraction, contrast-enhanced US, and motion-insensitive sequences for MRI. US is often the first imaging modality used in children with a suspected abdominal mass. Once a hepatic lesion is confirmed, multiphasic contrast-enhanced MRI is recommended for most lesions as the next imaging modality allowing full characterization of the lesion and assessment of the liver parenchyma. Contrast-enhanced CT can also be performed for assessment of pediatric focal liver lesions, especially in patients who have a contraindication to MRI. Contrast-enhanced US has shown promise to decrease the need for MRI or CT in some lesions such as hemangioma and focal nodular hyperplasia. Children with a history of malignancy can develop multiple types of hepatic lesions at various stages, including infections during an immunocompromised state, manifesting as focal liver lesions. Based on available limited data in the literature and the collective experiences of the Liver Imaging and Reporting Data System Pediatric Working Group, the authors provide guidelines for the imaging workup of pediatric focal liver lesions with an indication- and age-based approach and discuss the selection and performance of various imaging techniques and modalities. ©RSNA, 2022 See the invited commentary by Chojniak and Boaventura in this issue.

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.

Imaging of pediatric liver tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Primary hepatic malignancies are relatively rare in the pediatric population, accounting for approximately 1%-2% of all pediatric tumors. Hepatoblastoma and hepatocellular carcinoma are the most common primary liver malignancies in children under the age of 5 years and over the age of 10 years, respectively. This paper provides consensus-based imaging recommendations for evaluation of patients with primary hepatic malignancies at diagnosis and follow-up during and after therapy.

Pediatric Hepatic Cystic Lesions: Differential Diagnosis and Multimodality Imaging Approach.

When a pediatric hepatic cystic lesion is identified at imaging, the differential diagnosis may be broad, including developmental, infectious, neoplastic, and posttraumatic or iatrogenic causes. The location of a cystic lesion and its number, size, composition, and relationship to the biliary system are features that help in narrowing the differential diagnosis. An incidentally detected simple hepatic cyst is the most commonly encountered. Ciliated foregut cysts are typically located in hepatic segment IVa. The presence of multiple cysts should raise suspicion for fibropolycystic liver disease, a group of related lesions-including biliary hamartoma and choledochal cyst-caused by abnormal embryologic development of the ductal plate. Communication of the cystic lesion with the biliary tree can confirm the diagnosis of choledochal cyst. In a neonate with jaundice, a cystic lesion at the porta hepatis should raise suspicion for choledochal cyst versus cystic biliary atresia. Hepatic abscess can appear cystlike, though typically with internal contents. In an immunocompromised child, multiple cystlike lesions should raise concern for fungal microabscesses. A complex cystic mass in a young child should raise suspicion for mesenchymal hamartoma, which can evolve into undifferentiated embryonal sarcoma if untreated. Hepatic hematoma and biloma can appear cystlike in children with a history of trauma or recent intervention. In neonates with an umbilical vein catheter (UVC), an intrahepatic cyst along the course of the UVC should raise concern for infusate extravasation. Familiarity with imaging findings and clinical features is essential for achieving accurate diagnosis of pediatric hepatic cystic lesions, which in turn can guide appropriate clinical management. Online supplemental material is available for this article. ©RSNA, 2022.

Imaging Features of Hepatocellular Carcinoma in Children With and Without Underlying Risk Factors.

BACKGROUND. Pediatric hepatocellular carcinoma (HCC) is an aggressive malignancy for which imaging findings remain poorly described. In comparison with adult HCC, pediatric HCC more commonly occurs without underlying risk factors, and standardized surveillance guidelines for those with predispositions are lacking. OBJECTIVE. The purpose of this article was to evaluate imaging findings of nonfibrolamellar pediatric HCC and to identify associations between these imaging findings and the presence of predisposing factors. METHODS. This retrospective study included children (≤ 18 years) with histologically confirmed nonfibrolamellar HCC who underwent multiphase CT or MRI at one of four academic children's hospitals between July 2009 and April 2019. Surveillance regimens in children with predispositions were at the discretion of treating physicians. Clinical characteristics were recorded. Scan indications were classified as surveillance versus clinical signs and symptoms. Images from all sites were submitted to a cloud-based server. Two radiologists independently assessed imaging features of HCC, including tumor size, tumor in vein, Pre-Treatment Extent of Tumor (PRETEXT) stage, and LI-RADS major features of adult HCC. Imaging findings were compared between patients with and without predispositions. RESULTS. The study included 39 patients: 17 with predispositions (mean age, 10.5 ± 4.5 years; nine boys, eight girls) and 22 without predispositions (mean age, 11.3 ± 5.1 years; 12 boys, 10 girls). Scan indication was surveillance in 14/17 patients with predispositions versus 0/22 patients without predispositions (p < .001). Patients with versus those without predispositions had smaller tumor size (reader 1: 6.0 vs 11.9 cm [p = .003]; reader 2: 6.0 vs 12.9 cm [p < .001]) and less frequent tumor in vein (reader 1: 0% vs 41% [p = .002]; reader 2: 0% vs 36% [p = .006]). PRETEXT stage IV disease was observed in 18% (both readers) of patients with predispositions versus 50-55% of patients without predispositions. No LI-RADS major feature of adult HCC showed a significant difference in frequency between patients with and without predispositions for either reader (all p > .05). CONCLUSION. Among children with HCC, those with predispositions exhibited smaller and lower-stage tumors and less frequent tumor in vein, likely because of surveillance imaging. CLINICAL IMPACT. The study supports the role of routine surveillance imaging in children with HCC predispositions to facilitate earlier detection. Standardization of surveillance guidelines remains needed.

Liver iron quantification in children and young adults: comparison of a volumetric multi-echo 3-D Dixon sequence with conventional 2-D T2* relaxometry.

BACKGROUND: Magnetic resonance imaging (MRI)-based liver iron quantification is the standard of care to guide chelation therapy in children at risk of hemochromatosis. T2* relaxometry is the most widely used technique but requires third-party software for post-processing. Vendor-provided three-dimensional (3-D) multi-echo Dixon techniques are now available that allow inline/automated post-processing. OBJECTIVE: The purpose of our study was to evaluate the diagnostic accuracy of a volumetric multi-echo Dixon technique using conventional T2* relaxometry as the reference standard in a pediatric and young adult population. MATERIALS AND METHODS: In this retrospective study, we queried the radiology information system to identify all MRIs performed for liver iron quantification from July 2015 to January 2020. All patients had undergone T2* relaxometry on a 1.5-tesla (T) scanner for liver iron concentration (LIC) estimation. In addition, a 3-D multi-echo Dixon was performed using Siemens Healthineers LiverLab (Erlangen, Germany). Two readers independently estimated liver R2* and T2* on the multi-echo Dixon by drawing free-hand regions of interest on the scanner-generated R2* and T2* maps. Conventional T2*-relaxometry-based LIC was the reference standard. We estimated interobserver agreement by concordance correlation coefficient (CCC). We used Bland-Altman analysis and Pearson correlation coefficient (r) to compare LIC by the two methods. RESULTS: Fifty-four MRIs on 38 patients (22 females) were available for analysis. Mean patient age was 11.8 years (standard deviation [SD] 5.3 years). Reference standard LIC ranged 1.1-21.1 (median 6.8) mg/g dry weight of liver. The concordance between readers for T2* estimation using 3-D multi-echo Dixon was substantial (CCC 0.99, confidence interval 0.99-1.00). Bland-Altman plot showed that all observations were clustered around the zero bias line if the LIC average was ≤8 mg/g, and r was very strong (reader 1 r=0.93, reader 2 r=0.92, both P-values <0.001). With increasing LIC, there was a pattern of poor agreement on the Bland-Altman plot, with observations crossing the lower limits of agreement, and r was very weak (reader 1 r=0.05, P-value 0.84; reader 2 r=0.17, P-value 0.44). CONCLUSION: Vendor-based 3-D multi-echo Dixon allows for excellent interobserver correlation in liver T2* estimation. LIC estimated by this method has a very strong correlation with conventional T2* relaxometry if liver iron overload is mild-moderate (LIC ≤8 mg/g).

Outcomes based on histopathologic response to preoperative chemotherapy in children with bilateral Wilms tumor: A prospective study (COG AREN0534).

BACKGROUND: An objective of the Children's Oncology Group AREN0534 Study was to improve the survival of patients with bilateral Wilms tumors (BWT) by using preoperative chemotherapy of limited duration and tailoring postoperative therapy based on histopathologic response. The authors report outcomes based on postoperative histopathologic responses. METHODS: Patients with BWT received treatment with vincristine, dactinomycin, and doxorubicin for 6 or 12 weeks followed by surgery. Postoperative therapy was prescribed based on the highest risk tumor according to the International Society of Pediatric Oncology classification and the Children's Oncology Group staging system. RESULTS: Analyses were performed on data from 180 evaluable children. The 4-year event-free survival (EFS) and overall survival (OS) rates were 81% (95% CI, 74%-87%) and 95% (95% CI, 91%-99%), respectively. Seven patients who had completely necrotic tumors had a 4-year EFS rate of 100%. Of 118 patients who had tumors with intermediate-risk histopathology, the 4-year EFS and OS rates were 82% (95% CI, 74%-90%) and 97% (95% CI, 94%-100%), respectively. Fourteen patients who had blastemal-type tumors had 4-year EFS and OS rates of 79% (95% CI, 56%-100%) and 93% (95% CI, 79%-100%), respectively. Eighteen patients who had diffuse anaplasia had 4-year EFS and OS rates of 61% (95% CI, 35%-88%) and 72% (95% CI, 47%-97%), respectively; and the 4-year EFS and OS rates of 7 patients who had focal anaplasia were 71% (95% CI, 38%-100%) and 100%, respectively. There was no difference in the outcomes of patients who had different histopathologic subtypes within the intermediate-risk group (P = .54). CONCLUSIONS: A risk-adapted treatment approach for BWT results in excellent outcomes. This approach was not successful in improving the outcome of patients who had diffuse anaplasia.

Kidney Preservation and Wilms Tumor Development in Children with Diffuse Hyperplastic Perilobar Nephroblastomatosis: A Report from the Children's Oncology Group Study AREN0534.

INTRODUCTION: Diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) represents a unique category of nephroblastomatosis. Treatment has ranged from observation to multiple regimens of chemotherapy. Wilms tumors (WTs) develop in 100% of untreated patients and between 32 and 52% of treated patients. Renal preservation rates have not been previously reported. An aim of the Children's Oncology Group (COG) study AREN0534 was to prospectively evaluate the efficacy of chemotherapy in preserving renal units and preventing WT development in children with DHPLN. METHODS: Patients were enrolled through the COG protocol AREN03B2 with central radiological review. DHPLN was defined as the cortical surface of the kidney being composed of hyperplastic rests, with the entire nephrogenic zone involved, and with a thick rind capping all of one or both kidneys. Treatment was with vincristine and dactinomycin (regimen EE4A), with cross-sectional imaging at weeks 6 and 12. If the patient's disease was stable or decreasing, treatment was continued for 19 weeks. Renal preservation, WT development rates at 1 year, and overall survival (OS) are reported. RESULTS: Nine patients were enrolled (five females and four males), with a median age at enrollment of 10.22 months (range 2.92-29.11). One patient who was enrolled was deemed unevaluable because they did not meet the radiological criteria for DHPLN, resulting in eight evaluable patients. These eight patients had DHPLN confirmed via radiological criteria (all bilateral). Initial chemotherapy was EE4A for all eight patients, with seven of eight patients starting chemotherapy without tissue diagnosis.One patient who had an upfront partial nephrectomy was found to have DHPLN in the specimen and was subsequently treated with EE4A. All patients remained alive, with a median follow-up of 6.6 years (range 4.5-9.1). No patients were anephric; 14 of 16 kidneys were functioning (87.5%). Six of eight patients (75%) did not have WT on therapy, but two of these patients relapsed within 6 months of stopping therapy; both had favorable histology WT. One patient who was diagnosed with WT on therapy relapsed at 12 months (one of eight [12.5%]) and developed anaplastic histology. CONCLUSIONS: Chemotherapy for patients with DHPLN was effective in preserving kidney function. Five-year OS is excellent, however the ideal type and duration of chemotherapy to prevent WT development remains elusive.

Mammary Analogue Secretory Carcinoma of Submandibular Gland: A Case Report with Review of the Literature.

Secretory carcinoma (SC) is a rare salivary gland tumor and has been recently included in the fourth edition of the World Health Organization classification of head and neck tumors. To understand the histopathologic findings and clinical behavior of mammary analogue secretory carcinoma (MASC) of the submandibular gland in a 23 year old female. MASC is an intriguing and rare malignant salivary gland tumor first described in 2010. It shares histologic, immunohistochemical and genetic features with secretory carcinoma of the breast. The clinical behavior of MASC ranges from slowly growing tumors to aggressive tumors that can cause widespread metastasis. Many cases of MASC were discovered in archived cases previously classified as pleomorphic adenoma, acinic cell carcinoma, mucoepidermoid carcinoma, and adenocarcinoma. They are only a few reported in submandibular gland. MASC is a newly recognized variant of salivary gland malignancy. Further research is needed to better delineate its overall prevalence and to define an appropriate treatment algorithm for this new clinical entity.

Idiopathic Pulmonary Hemosiderosis: An Unexplored Cause of Treatment Refractory Pediatric Iron Deficiency Anemia.

Idiopathic pulmonary hemosiderosis (IPH) is an unusual cause of pediatric iron deficiency anemia (IDA) characterized by alveolar hemorrhage leading to hemosiderin deposition and fibrosis in the lungs. Though the typical triad of presentation is hemoptysis, IDA, and lung opacities on thoracic radiographs, often the sole manifestation of IPH may be severe IDA in children.

Impact of the First Generation of Children's Oncology Group Clinical Trials on Clinical Practice for Wilms Tumor.

Refinements in surgery, radiation therapy, and chemotherapy since the mid-20th century have resulted in a survival rate exceeding 90% for patients with Wilms tumor (WT). Although this figure is remarkable, a significant proportion of patients continue to have event-free survival (EFS) estimates of <75%, and nearly 25% of survivors experience severe chronic medical conditions. The first-generation Children's Oncology Group (COG) renal tumor trials (AREN '0'), which opened to enrollment in 2006, focused on augmenting treatment regimens for WT subgroups with predicted EFS <75% to 80%, including those with the adverse prognostic marker of combined loss of heterozygosity (LOH) at chromosomes 1p/16q, pulmonary metastasis with incomplete lung nodule response after 6 weeks of chemotherapy, bilateral disease, and anaplastic histology. Conversely, therapy was reduced for patient subgroups with good outcomes and potential for long-term toxicity, such as those with lung metastasis with complete lung nodule response after 6 weeks of chemotherapy. This article summarizes the key findings of the first-generation COG renal tumor studies and their implications for clinical practice.