Peds - Wilms Tumor

About this video

• Video Title: Peds - Wilms Tumor
• Channel: Rad Onc Talks
• Speakers: Ria
• Duration: 01:08:39

Overview

This video provides a comprehensive overview of Wilms tumor, a common embryonic kidney cancer in children. It covers the tumor's background, epidemiology, comparison with neuroblastoma, staging, histological classifications (favorable and unfavorable), risk stratification, and treatment paradigms including surgery, chemotherapy, and radiotherapy. The presentation emphasizes the importance of understanding these factors for effective management and patient outcomes.

Key takeaways

• Wilms Tumor vs. Neuroblastoma: The video differentiates Wilms tumor from neuroblastoma, highlighting their distinct origins, appearances, clinical presentations, and metastatic patterns, which are crucial for accurate diagnosis and management.
• Genetics and Risk Factors: It explains the genetic underpinnings of Wilms tumor, including specific syndromes like WAGR and Denys-Drash, and discusses genetic markers (WT1, WTX, 1p/16q loss of heterozygosity) that influence prognosis and treatment intensity.
• Staging and Risk Stratification: The presentation details the POSTOP (post-operative) staging system (Stages 1-5) for Wilms tumor and outlines a risk stratification system for favorable histology, which guides treatment intensity.
• Treatment Paradigm: The standard US approach involves upfront radical nephrectomy followed by risk-adapted chemotherapy (e.g., E4A, DD4A regimens) and radiation therapy, with indications and doses clearly specified for different stages and histologies.
• Evidence-Based Management: The video reviews key clinical trials (e.g., ARNT0532, ARNT0533, ARNT0534) that support the current treatment strategies for various risk groups of Wilms tumor, including bilateral disease.

Wilms tumor is staged post-operatively based on the extent of disease and surgical findings, following the standard Group Staging system. The stages are as follows:

• Stage 1: The tumor is completely resected with negative surgical margins, limited to the kidney, with no involvement of renal sinus vessels. The renal capsule is intact, and there was no tumor rupture or biopsy performed during surgery.
• Stage 2: The tumor is completely resected with negative margins, but there is some extension beyond the kidney. This includes penetration of the tumor capsule or invasion into the soft tissues of the renal sinus. If tumor is present in blood vessels within the nephrectomy specimen that are outside the renal parenchyma (including renal sinus vessels), it is also considered Stage 2.
• Stage 3: This stage applies if there is residual tumor confined to the abdomen following surgery. Specific criteria that lead to Stage 3 include:
  • Subtotal resection or positive surgical margins.
  • Involvement of abdominal lymph nodes.
  • Unresectable disease at the time of surgery.
  • Rupture of the tumor capsule or spillage of tumor into the abdomen during surgery.
  • Peacemeal resection (removing the tumor in pieces rather than en bloc).
  • Requirement for pre-operative chemotherapy (indicating unresectable disease initially).
  • Peritoneal implants or involvement of the peritoneum.
  • A biopsy was performed, leading to spillage into the abdomen.
• Stage 4: This stage is defined by distant metastases, which can include lymph nodes outside the abdomen or pelvis.
• Stage 5: This stage is specifically for bilateral renal involvement present at the time of diagnosis.

Primary Indications for Radiation Therapy in Wilms Tumor:

Flank Radiation:

Flank radiation is the standard treatment for localized residual disease in the flank after surgery. The primary indications include:

• Stage 3 or 4 Favorable Histology Wilms Tumor: These stages indicate residual disease in the abdomen, involvement of lymph nodes, or distant metastases, all of which warrant radiation to the affected flank.
• Any Stage Unfavorable Histology Wilms Tumor: Unfavorable histology, characterized by anaplasia, is considered a high-risk feature, and patients with this histology generally receive radiation regardless of stage.
• Focal Anaplasia: Even if the overall stage is lower, the presence of focal anaplasia (a component of unfavorable histology) can be an indication for flank radiation.

Whole Abdomen Radiation:

Whole abdomen radiation is reserved for more extensive disease or specific complications to ensure complete coverage of potentially affected areas. The indications are:

• SPAR mnemonic: This acronym represents the conditions that necessitate whole abdomen radiation:
  • Spillage: If there was spillage of tumor cells into the peritoneal cavity during surgery (e.g., from a biopsy or tumor rupture).
  • Peritoneal Seeding: Evidence of tumor cells spread within the peritoneal cavity.
  • Ascites: Presence of malignant ascites.
  • Rupture: Pre-operative rupture of the tumor capsule.
• Peritoneal Implants: Gross disease or peritoneal implants are also indications for whole abdomen radiation.

It's important to note that the decision to use whole abdomen radiation is carefully considered due to the potential long-term side effects, and it's typically reserved for cases with a high risk of intra-abdominal recurrence or spread.

Topics and Tags for Detailed Exploration:

Topics:

• Pediatric Oncology: Focus on cancers specific to children.
• Nephrology/Urology: Understanding kidney anatomy and function in relation to tumors.
• Medical Imaging: Interpretation of ultrasound, CT, and MRI in diagnosing abdominal masses.
• Pathology: Histological subtypes, genetic markers, and their prognostic significance.
• Radiation Oncology Techniques: Planning, dose delivery, and field setup for abdominal and thoracic irradiation.
• Medical Genetics: Role of genetic syndromes and mutations in cancer development.
• Clinical Trial Design: Understanding how research studies inform treatment protocols.
• Differential Diagnosis: Distinguishing between similar pediatric abdominal tumors.
• Cancer Staging Systems: Application and interpretation of staging for therapeutic decisions.
• Treatment Modalities: Surgery, chemotherapy, and radiotherapy in pediatric cancer care.

Tags:

• Wilms Tumor
• Pediatric Cancer
• Nephroblastoma
• Embryonal Kidney Tumor
• Neuroblastoma
• Pediatric Oncology
• Radiation Oncology
• Chemotherapy
• Pediatric Surgery
• Abdominal Mass
• Childhood Cancer
• Renal Tumors
• WAGR Syndrome
• Denys-Drash Syndrome
• Beckwith-Wiedemann Syndrome
• WT1 Gene
• WTX Gene
• 1p Loss of Heterozygosity
• 16q Loss of Heterozygosity
• Histology (Favorable, Unfavorable, Anaplasia)
• Staging (Stage 1-5)
• Risk Stratification
• Adjuvant Therapy
• Neoadjuvant Therapy
• Radical Nephrectomy
• Nephron-Sparing Surgery
• E4A Regimen
• DD4A Regimen
• UH1/UH2 Regimens
• Flank Radiation
• Whole Abdomen Radiation
• Lung Metastasis
• Claw Sign
• Medical Education
• Rad Onc Talks

The video highlights several key differences in the presentation and imaging of Wilms tumor and neuroblastoma, which are crucial for distinguishing between these two common pediatric abdominal masses:

Presentation:

• Wilms Tumor:
  • Typical Presentation: Usually presents as a painless abdominal mass.
  • Other Symptoms: Can sometimes be associated with abdominal pain, fever, hematuria (blood in urine), anemia, or hypertension (high blood pressure).
  • Age: Most common in children under 5 years old, with a median age of diagnosis around 3-4 years.
  • Laterality: Primarily affects one kidney (unilateral), though bilateral presentation occurs in about 4-8% of cases at a slightly younger age.
• Neuroblastoma:
  • Typical Presentation: Can present with a variety of symptoms due to hormone secretion (catecholamines).
  • Other Symptoms: Associated with specific signs like "raccoon eyes," "blueberry muffin sign," Hutchinson's sign, opsoclonus-myoclonus syndrome, and Horner's syndrome.
  • Age: Most common malignancy in infants and a frequent pediatric solid tumor. The median age of diagnosis is around 1 year old.
  • Laterality: Can originate from adrenal glands or sympathetic ganglia in the abdomen or mediastinum, and frequently crosses the midline.

Imaging:

• Wilms Tumor:
  • Appearance: Typically appears as a well-defined mass within the kidney, often with smoother borders.
  • Calcifications: Less likely to have calcifications, though they can occur due to hemorrhage.
  • Renal Architecture: Disrupts the intrinsic renal architecture because it arises from the kidney itself.
  • "Claw Sign": A characteristic finding where the tumor displaces the enhancing renal tubules, making it appear as if the kidney is forming a "claw" around the tumor.
  • Location: Usually confined to one side of the abdomen and rarely crosses the midline.
• Neuroblastoma:
  • Appearance: Tends to be a heterogeneous mass with less defined, more irregular borders.
  • Calcifications: Often contains calcifications.
  • Renal Architecture: Does not arise from the kidney; it displaces the kidney but does not distort its internal architecture.
  • Invasion: Can extend into surrounding tissues.
  • Location: Frequently crosses the midline and can originate from various sites like the adrenal glands or sympathetic chain.

Wilms tumor is associated with several genetic syndromes, which are linked to specific genetic alterations and confer an increased risk of developing the tumor. The primary syndromes discussed are:

1. WAGR Syndrome:

   • Genetic Underpinning: Caused by a deletion on chromosome 11 at the 11p13 locus. This deletion typically involves the WT1 gene (Wilms Tumor 1 suppressor gene) and the PAX6 gene (also known as the aniridia gene).
   • Presentation: Characterized by a constellation of features: Wilms tumor, Aniridia (absence of the iris), Genitourinary anomalies (such as hypospadias or undescended testes in males), and Retardation (intellectual disability or developmental delays).
   • Risk: The risk of developing Wilms tumor in WAGR syndrome is significant, around 30%.

2. Denys-Drash Syndrome:

   • Genetic Underpinning: Results from a point mutation in the WT1 gene, specifically in its zinc finger regions, located at the 11p13 locus.
   • Presentation: This syndrome presents with:
     • Wilms tumor.
     • Progressive renal disease leading to nephrotic syndrome and eventually renal failure in infancy.
     • Male pseudohermaphroditism (ambiguous genitalia).
   • Risk: Denys-Drash syndrome confers the highest risk of Wilms tumor, with estimates ranging from 50% to 90%.

3. Beckwith-Wiedemann Syndrome:

   • Genetic Underpinning: Associated with alterations in the 11p15 locus, which affects imprinting patterns of several genes, including IGF2 (Insulin-like Growth Factor 2) and H19.
   • Presentation: Characterized by macrosomia (large body size), hemihypertrophy (overgrowth of one side of the body), macroglossia (large tongue), organomegaly (enlarged organs), and sometimes ear pits or creases.
   • Risk: While Beckwith-Wiedemann syndrome is associated with an increased risk of various childhood cancers, the risk specifically for Wilms tumor is lower, estimated at around 5%.

The video emphasizes that WAGR and Denys-Drash syndromes, both linked to alterations at the 11p13 locus and impacting the WT1 gene, carry a substantially higher risk of Wilms tumor development compared to Beckwith-Wiedemann syndrome.