eBulletin Newsletter

NCCN Flash Updates: NCCN Guidelines Updated for Wilms Tumor

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™) for Wilms Tumor. These NCCN Guidelines® are currently available as Version 1.2024.

Link directly to the Updates section of the NCCN Guidelines: Wilms Tumor

Global Changes

  • References updated throughout the Guidelines.
  • "Wilms Tumor", "FHWT", and "Wilms Tumor with Anaplasia" specified where needed.
  • Footnote f modified: Conditions that predispose to the development of WT include genetic disorders such as Denys-Drash, WAGR, Beckwith-Wiedemann, Frasier, and Perlman syndromes; contralateral nephrogenic rests in children <12 months. Ten percent to 33% of WT occurs in children with predisposing conditions. Children with known predisposing conditions should be screened for WT with PE and abdominal US every 3 months until 8 7 years of age (ie, all of year 7 6). See Principles of Cancer Risk Assessment and Counseling (WILMS-I).
  • Footnote q modified: Principles of Chemotherapy for FHWT Wilms Tumor (WILMS-G).
  • Footnote s modified: Principles of Radiation Therapy for FHWT Wilms Tumor (WILMS-H).
  • All instances of "predisposition syndrome" have been changed to "predisposing condition" throughout the Guidelines.

INTRO-1

  • Statement removed: The NCCN Guidelines for Wilms Tumor (Nephroblastoma) only address favorable histology Wilms tumor (FHWT) at this time.
  • Epidemiology of Wilms Tumor
    • Bullet 1, modified: WT accounts for 5% of childhood cancers and is the most common primary renal tumor in children (accounts for >90% of renal tumors in patients <20 years). Five-year survival for these patients is >90% with appropriate treatment. However, outcome of some groups, particularly those with diffuse anaplastic WT, remains poor. This guideline will include treatment pathways for anaplastic WT in a future version.
  • Clinical Presentation
    • Bullet 9 modified: If a predisposing condition is present, routine screening for WT is recommended with physical exam (PE) and renal US every 3 months until 8 7 years of age (ie, all of year 7 6).

INTRO-2

  • Bullet 7 modified: Recommend referral to infertility risk/fertility preservation counseling for patients treated with chemotherapy; strongly encourage prior to treatment with regimen M, I, or whole abdominal irradiation (WAI).

WILMS-1

  • Initial Evaluation
    • Bullet 6
      • Footnote d applied
      • Bullet modified: Chest CT with or without contrast
    • Bullet added: Consider oncofertility counseling

WILMS-2

  • Initial Treatment, No predisposing condition
    • Tumor resectable, pathway added: Adjuvant Treatment for unilateral Wilms tumor with anaplasia
    • Tumor not resectable, pathway added: Neoadjuvant Treatment for Unresectable Unilateral Wilms tumor with No Predisposing Condition and with anaplasia

WILMS-4

  • Footnote x modified: Patients with extrapulmonary metastases were switched to Regimen M on AREN0533 trial, but results have not been published. but when compared to outcomes with DD4A on NWTS-5, a significant benefit was not demonstrated (4-year EFS 76% for Regimen M vs. 65% for DD4A [P = .26]; 4-year OS 89% for Regimen M vs. 86.5% for DD4A) (Benedetti DJ, et al. Cancer 2024;130:947-961). (Also for WILMS-5 B)

WILMS-5

  • Pathway added: Wilms tumor with anaplasia

WILMS-5B

  • Footnote aa added: If anaplasia is present in resected specimen, go to WILMS-11.
  • Footnote dd added: If imaging shows tumor progression (increase in size), nephrectomy OR rebiopsy (to evaluate for anaplasia or rhabdomyomatous changes) should be performed.

WILMS-6

  • Histology results, pathway added: Wilms tumor with anaplasia (Also for WILMS-7, WILMS-8, WILMS-9)

WILMS-6A

  • Footnote kk modified: Molecular biomarkers were not used to direct therapy on in the AREN0534 trial. (Also for WILMS-7A, WILMS-8, WILMS-8B, WILMS-9, WILMS-9B)
  • Footnote ll modified: Use of biomarkers from post-chemotherapy tumor has not been established to correlate with outcome, nor has it been used to direct therapy in a prospective trial. Outcomes on of AREN0534 study were excellent despite this. Regimen M was not studied in this population. (Also for WILMS-7A)

WILMS-8

  • Footnote oo added: If any of the resected tumors has anaplasia, see WILMS-13. (Also for WILMS-9)
  • Footnote removed: Stage I–II with complete necrosis can switch to Regimen EE4A.

WILMS-8B

  • Footnote rr modified: If 6-week biopsy reveals blastemal predominant (all stages), then use Regimen I and re-evaluate at 12 weeks; otherwise continue Regimen VAD for 6 weeks and re-evaluate at 12 weeks. Revised Regimen UH-2 if week 6 biopsy shows anaplasia (See WILMS-10) (Also for WILMS-9B)

WILMS-10

  • New page added

WILMS-11

  • New page added

WILMS-12

  • New page added

WILMS-13

  • New page added

WILMS-B

WILMS-D (1 of 4)

  • General Principles
  • Bullet 4, footnote a added: For patients who are enrolled on a clinical trial, review nodal sampling requirements in the protocol.
  • Principles of surgery, figure added: Locations of Suggested Lymph Node Sampling
    • Footnote b added: Aldrink JH, Romao R, Ehrlich PF, et al. Critical elements of radical nephroureterectomy for pediatric unilateral renal tumor. Semin Pediatr Surg 2023;32:151339. With permission from Elsevier.

WILMS-G (1 of 4)

  • Chemotherapy Regimens, bullet added: Revised Regimen UH-2: 19 doses of vincristine, 5 doses of doxorubicin, 5 doses of cyclophosphamide, 5 cycles of 4 daily doses of cyclophosphamide, 5 doses of carboplatin, 5 cycles of 4 daily doses of etoposide, 2 cycles of 5 daily doses of irinotecan. This regimen is used for stage 2–4 Wilms tumor with diffuse anaplasia and for stage 4 Wilms tumor with focal anaplasia.

WILMS-G (2 of 4)

  • Chemotherapy Toxicity
    • Bullet 2 modified: Doxorubicin—which is included in Regimens DD4A, VAD, M, and I, and UH-2—can cause myocardial damage, correlated to the cumulative dose of the drug. Although the cumulative dose of doxorubicin on these regimens is 150 to 225 250 mg/m2, younger children, especially girls, are more susceptible to doxorubicin cardiotoxicity. An echocardiogram to assess cardiac function should be performed prior to the first dose of doxorubicin and then prior to exceeding a cumulative dose of 200 mg/m2 and at the end of treatment to monitor cardiac function.
    • Bullet 3 modified: Cyclophosphamide and etoposide—which are included in Regimens M, and I, and Revised Regimen UH-2—increase the risk of acute toxicities, such as myelosuppression, and of long-term effects, including infertility and secondary cancers later in life. The cumulative dose of cyclophosphamide is lower in Regimen M (8.8 g/m2) than in Regimen I (11.88 g/m2). The cumulative dose of etoposide is 2 g/m2 or less in Regimens M and I. Doses more than 7g/m2 of cyclophosphamideCumulative doses greater than a 4 g/m2 cyclophosphamide equivalent dose are associated with a risk of oligospermia and azoospermia.
    • Bullet 4 added: The UH-1 and UH-2 regimens used to treat anaplastic Wilms tumor are the most toxic regimens used to treat Wilms tumor. Several toxicity-related deaths occurred in patients treated with UH-1, but there were no toxic deaths on the revised UH-2 regimen.
    • Bullet 5 added: 0.8% of patients experience severe hepatopathy, including sinusoidal obstruction syndrome, which presents with abdominal distension, ascites, hepatomegaly, elevated transaminases and bilirubin and thrombocytopenia. Severe hepatopathy occurred most often after a course of vincristine and dactinomycin, but radiation to the liver also contributes. Treatment could be safety reintroduced in the vast majority of patients after recovery.
  • Supportive Care
    • Bullet 2 modified: Colony-stimulating factors (filgrastim or pegfilgrastim) are not necessary after doses of myelosuppressive agents in Regimens EE4A, DD4A, and VAD, but should be considered for cycles of cyclophosphamide and etoposide and cyclophosphamide, doxorubicin, and vincristine and cycles of cyclophosphamide, carboplatin, and etoposide in Regimen M, and Regimen I, and Regimen UH-2.

WILMS-G (3 of 4)

  • Treatment Augmentation for FHWT
    • Bullet removed: EFS for patients with stage IV FHWT and lung metastases only who did not achieve a CR of the lung metastases after 6 weeks of Regimen DD4A on AREN0533 was improved compared to the NWTS-5 historical control, but questions have been raised about the comparability of the control group.
    • Bullet 4 modified: Results from treating patients with stage IV FHWT and extrapulmonary metastases with Regimen M have not been published. Patients with extrapulmonary metastases treated with Regimen M on AREN0533 trial had higher 4-year EFS than patients treated with DD4A on NWTS-5 trial (76% vs. 64%, P = .26), but overall survival was the same.
    • Bullet 6 modified: Regimen M resulted in 4-year EFS and OS of 88.5% and 95.4% for patients with SIR of lung metastases.These outcomes should be balanced against the increased risk of toxicities and concerns with the historical comparison cohort and limitations of using a historical control as a comparator.

WILMS-I (1 of 5)

  • Bullet 5, sub-bullet modified: REST, TRIM28, FBXW7, NYNRIN, KDM3B, XPO5, CHEK2a, PALB2a, and DICER1
  • Bullet 7, sub-bullet modified: The Pediatric Cancer Working Group of the American Association for Cancer Research recommends renal US every 3 mo until 8 7 years (ie, all of year 7 6).

WILMS-I (2 of 5)

  • Footnote b modified: Patients with these syndromes should have surveillance for WT with renal US, including the adrenal glands, every 3 months until 8 7 years (ie, all of year 7 6). (Also for WILMS-I 3)

WILMS-J (1 of 2)

  • New page added

WILMS-J (2 of 2)

  • New page added

 

For the complete updated versions of the NCCN Guidelines, NCCN Guidelines with NCCN Evidence Blocks™, the NCCN Drugs & Biologics Compendium (NCCN Compendium®), the NCCN Biomarkers Compendium®, the NCCN Chemotherapy Order Templates (NCCN Templates®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), please visit NCCN.org.

To view the NCCN Guidelines for Patients®, please visit NCCN.org/patientguidelines.

Free NCCN Guidelines apps for iPhone, iPad, and Android devices are now available! Visit NCCN.org/apps.

About NCCN Flash Updates™

NCCN Flash Updates™ is a subscription service from NCCN that provides timely notification of updated and new information appearing in the NCCN Guidelines, the NCCN Compendium®, and other NCCN Content.

Subscribe to NCCN Flash Updates™

Third Party Content: The NCCN Content may contain content (such as figures, tables or illustrations) that NCCN licenses from third parties as displayed on NCCN Third Party Content site: private.filesanywhere.com/fs/v.aspx?v=8a6d65cfa19ea4bda0a3&C=6241. Licensee shall be solely responsible for obtaining permissions from each such third party to use any such Third Party Content in the Permitted Works. 

Access information on permissions and licensing of NCCN Content

Users may unsubscribe from Flash Updates at any time by contacting us. NOTE: The subscription fee for NCCN Flash Updates™ is non-refundable.

3025 Chemical Road, Suite 100, Plymouth Meeting, PA 19462
Phone: 215-690-0300
Fax: 215-690-0280
Copyright © National Comprehensive Cancer Network, All Rights Reserved.

No portion of this Site or any NCCN Content may be copied, transferred, reproduced, modified, or otherwise used for any purpose without NCCN’s express written permission.
See Legal Notices Section for additional notices and terms governing your use of this Site.