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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 Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™) for Wilms Tumor (Nephroblastoma). These NCCN Guidelines^® are currently available as Version 1.2023.

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

Global Changes

• References updated throughout the Guidelines
• "Combined" added to all instances of LOH at 1q and 16q

• Preference Stratification of Chemotherapy Regimens: When two chemotherapy regimens are options for a specific setting, the NCCN Panel has decided which regimen is Preferred and which is an Other Recommended Regimen.

INTRO-1

• Epidemiology of Wilms Tumor
  • 1st bullet modified: ...However, outcome of some groups, particularly those with diffuse anaplastic WT, remains poor. This guideline does notwill include treatment pathways for anaplastic WT at this timein a future version.
• Clinical Presentation
  • 2nd bullet modified: A healthy-appearing child with an abdominal massis more likely to have WT, whereas an ill-appearing child may havea child withneuroblastomatends to be ill-appearing at presentation. (Also WILMS-A)
  • 6th bullet modified: WT is associated with genetic predisposition syndromespredisposing conditions in 10%-15% of cases, such as Denys-Drash Beckwith-Wiedemann syndrome (male pseudohermaphroditism and glomerulopathy); WAGR syndrome (WT, aniridia, genitourinary abnormalities, and range of intellectual disability); andBeckwith-Wiedemann syndrome (macroglossia, hemihyperplasia, gigantism, and umbilical hernia).; WAGR syndrome (WT, aniridia, genitourinary abnormalities, and range of developmental delay); and Denys-Drash syndrome (male pseudohermaphroditism and glomerulopathy), in 10%–15% of cases.
  • 9th bullet modified: If a predispositionpredisposing condition is present, routine screening for WT is recommended with physical exam (PE) and renal US every 3 months until at least 8 years of age (ie, all of year 7).
  • 10th bullet modified: Compared with children with unilateral disease, children with multifocal/bilateral disease present at a younger age than children with unilateral disease, and are often identified as part of a surveillance program for patients with a predisposing condition.

INTRO-2

• Treatment
  • 3rd bullet modified: Imaging studies, pathology, and tumor genetic testing results that are used to determine stage and risk group should be performed byin consultation with experienced specialists.
  • 7th bullet modified: Referral for Cancer Predisposition Consultation is recommended when availableappropriate for all patients with WT and strongly encouraged for patients with multifocal or bilateral WT.
  • 8th bullet modified: Recommend referral to infertility risk/fertility preservation counseling for all patients treated with chemotherapy...

WILMS-1

• Initial Evaluation
  • 3rd bullet, sub-bullet modified Consider PT/PTT and, if abnormal, screen for acquired von Willebrand disease
• Footnote c added: Consider screening for acquired von Willebrand disease if prothrombin time/partial thromboplastin time (PT/PTT) is abnormal
• 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 20%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 at least 8 years of age (ie, all of year 7). Consider germline testing for patients with physical findings consistent with a predisposition condition. (Also WILMS-2)

WILMS-2

• Footnote n modified: Biopsy is not indicated for patients with bilateral WT and/or predisposing condition,Initial biopsy is not recommended for children with imaging findings of bilateral renal tumors, or unilateral tumor and known predisposition syndrome, but biopsy should be considered for children in those categories who also are >10 years of age, or with concern for pathology other than WT.

• Footnote o modified: Perform molecular analysis to identify loss of heterozygosity (LOH) of 1p, 16q, 11p, and 1q gain. If tumor is not WT, refer to appropriate specialist or NCCN Guidelines, if available. Other malignant renal tumors include clear cell sarcoma of the kidney (CCSK), rhabdoid tumor, congenital mesoblastic nephroma, renal cell carcinoma, or renal medullary carcinoma.

WILMS-3

• Footnote p modified: Initial Risk Group based on histology, stage, age, and tumor weight. Risk Assessment for FHWT (WILMS-F) (Also WILMS-4, WILMS-4A)
• Footnote t modified: Radiation therapy (RT) to the primary site is often given 10 to 14 days after surgery. We recognize the concern for overlapping fields if the abdomen and lung are treated at different times and recommend planning for possible abdominal and lung fields with initial abdominal RT planning, even if lung RT ultimately not given, to avoid potential of overlapping fields.However, consider patient factors when deciding about the timing of RT (eg, age of patient, need to assess response of lung metastases to chemotherapy), when giving whole abdomen and whole lung RT. Local stage III refers to staging at the primary tumor regardless of metastases. (Also WILMS-4, WILMS-4A, WILMS-5B, WILMS-6A, WILMS-7A, WILMS-8, WILMS-8B, WILMS-9, WILMS-9B)
• Footnote removed: Regimen M has a greater risk of increased toxicity and late effects, including second cancers and infertility related to cyclophosphamide and etoposide. There are issues with the historical comparison group that has been used to justify augmenting therapy with Regimen M. (Also WILMS-4, WILMS-4A, WILMS-5, WILMS-5A)

WILMS-5

• Neoadjuvant Therapy
  • Resectable, Nephrectomy with regional LN sampling, arm modified: Lung-only metastases (re-image week 6) (Also WILMS-5A)
• Molecular/Imaging Results
  • Lung-only metastases, arm modified: No combined LOH at 1p and 16q, 1q gain positive, and CR of lung metastases at week 6
• Radiation Therapy, bullet removed: Post-op (Also on WILMS-5A, WILMS-6, WILMS-7, WILMS-8, WILMS-9)

WILMS-5B

• Footnote removed: Reimage primary and metastatic sites. (Also WILMS-6A, WILMS-8 and WILMS-8B)
• Footnote removed (and moved to WILMS-G 3 of 4): Regimen M resulted in EFS and OS of 88.5% and 94.5% 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.

WILMS-6

• Neoadjuvant Therapy
  • Treatment modified: Regimen EE4A (re-image week 6), not resectable by partial nephrectomy at 6 weeks (Also WILMS-7)
  • Treatment modified: Resectable by partial nephrectomy week 6, Partial nephrectomy, when feasible, or total nephrectomy with regional LN sampling, Pathology is FHWT

WILMS-6A

• Footnote gg modified: Indications for total complete nephrectomy for unilateral WT (with predisposing condition) are described in Principles of Surgery. (Also WILMS-7A)
• Footnote hh modified: Tumors should be resected at by week 12 at the latest (partial or total nephrectomy), because continued significant tumor shrinkage was not seen after that point in treatment. (Also WILMS-7A, WILMS-8B, WILMS-9B)

WILMS-7

• General: "of renal tumors" added to multiple arms for clarity (Also WILMS-9, WILMS-9A)
• Neoadjuvant therapy, Regimen VAD (re-image at 6 weeks) arm modified: Not resectable by partial nephrectomy at 6 weeks (Also WILMS-8, WILMS-8A, WILMS-9, WILMS-9A)
• Header modified: Histology Results for FHWT (Also WILMS-8 and WILMS-9)

WILMS-8

• Neoadjuvant Therapy
  • Resectable by bilateral partial nephrectomy at 6 weeks arm modified: Partial nephrectomy (one or both sides) when feasible or total nephrectomy (after 12 weeks), with regional LN sampling, Pathology is FHWT (Also WILMS-9)

• Histology Results for FHWT
  • Arm modified: Stage I and not blastemal predominant or Stage I-II with complete necrosis
• Footnote oo modified: Stage I-II with complete necrosis can switch to Regimen EE4A.

WILMS-8A

• Histology Results header removed (Also WILMS-9A)
• Radiation Therapy header removed
• Neoadjuvant Therapy
  • Complete response arm added (Also WILMS-9A)
  • Not resectable by partial nephrectomy at 6 weeks arm modified: Less than a partial response in either kidney or progression (Also WILMS-9A)
    • Arm modified: bilateral open biopsies recommended if partial nephrectomy not feasible (Also WILMS-9A)
• Adjuvant Therapy
  • Less than a complete response arm modified: Partial nephrectomy (one or both sides) when feasible or total nephrectomy (after 12 weeks) with regional LN sampling, Pathology is FHWT (Also WILMS-9A)

WILMS-8B

• Footnote qq added: If 6-week biopsy reveals blastemal predominant (all stages), then use Regimen I and reevaluate at 12 weeks; otherwise continue Regimen VAD for 6 weeks and reevaluate at 12 weeks. (Also WILMS-9B)

WILMS-B

• Goals of Imaging, 3rd bullet modified: Assess for the presence of two kidneys and determine the location of the involved kidneytumor (renal fossa vs. ectopic)

WILMS-D (1 of 4)

• General Principles
  • 1st bullet added: Decisions about complex surgery should be discussed with surgeons/urologists with experience managing such issues as complex venous tumor thrombi or nephron-sparing surgery (NSS).
• Contraindications to Primary Resection
  • 1st bullet modified: High risk of renal failure for those with germline WT1 mutations (Denys-Drash, WAGR) or bilateral WT.Overall risk of long-term renal failure in patients with unilateral, nonsyndromic WTis <1%.

WILMS-D (2 of 4)

• Surgical Management: Abdominal Cavity, 6th bullet modified: Perform LN sampling from renal hilum, pericaval/para-aortic regions. Additionally, regional LNs should be sampled from the renal hilum and paracaval and para-aortic regions. Involved or suspicious LNs should be removed, but a formal LN dissection is not necessary.
• Summary of Surgical Approach in Unilateral Tumors in Patients with Predisposing Conditions, 4th bullet modified: In the unilateral predisposed setting, less than partial response at 6 weeks of chemotherapy required total nephrectomy in AREN0534. Although in AREN0534, radical nephrectomy may have been recommended for unilateral tumors in patients with predisposing conditions who had less than a partial response, the decision about radical versus partial nephrectomy is also based on the anatomic feasibility for partial nephrectomy and less than a partial response is not a contraindication against attempted partial nephrectomy or continuing pre-surgical chemotherapy to week 12.

WILMS-F

• Final Risk Group: Page links added to each risk group

WILMS-G (2 of 4)

• Chemotherapy Toxicity: New section added

WILMS-G (3 of 4)

• Treatment Augmentation
  • 2nd bullet modified: Regimen M includes 4 cycles of cyclophosphamide and etoposide., which significantly increase the risk of infertility and secondary leukemia.
  • 7th bullet added: Regimen M resulted in 4-year EFS and OS of 88.5% and 95.4% 94.5% 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.

WILMS-H (1 of 3)

• Radiotherapy Timing
  • 1st bullet modified: RT should be started by day 10 after definitivesurgery (preferred) but no later than day 14, if surgery is designated day 0. A later radiation start is linked to increased risk of abdominal recurrence in some studies.
  • 2nd bullet added: Consider patient factors when deciding about the timing of RT (eg, age of patient, need to assess response of lung metastases to chemotherapy), when giving whole abdomen and whole lung RT.
• Flank Radiation
  • 1st bullet modified: Indications: Flank RT for patients diagnosed with either local stage III or stage IV with local stage III.Discussion with the surgeon about at-risk areas is necessary for all patients and particularly in the setting of intraoperative spillage, whether focal or diffuse (as determined by the surgeon). If focal spill confirmed to be localized and contained within a flank field, then flank RT is recommended.See ST-1 for staging criteria. Local stage III refers to staging at the primary tumor regardless of metastases.
  • 3rd bullet, sub-bullet modified: Indication: If positive LNs are positivefound and resected, an additional boost is given to unresected nodes.
  • 4th bullet modified: Delivery of RT is recommended with photons for flank, whole abdomen, and whole lung. Shielding of the contralateral kidney should be considered in the flank area. Boost modality should be more conformal with three-dimensional conformal RT (3D-CRT), intensity-modulated RT (IMRT), or protons.
• Whole Abdominal Irradiation (WAI)
  • 1st bullet modified: Indications: Cytology-positive ascites; preoperative tumor rupture; peritoneal seeding; and diffuse surgical spillage. Discussion with the surgeon about at-risk areas is necessary for all patients and particularly in the setting of both intraoperative spillage (whether focal or diffuse) and preoperative rupture (as determined by the surgeon).If preoperative rupture has occurred, then WAI is recommended. See ST-1 for staging criteria.
• Footnote a modified: Recommend fertility counseling for female patients receiving flank RT and/or WAI, which may cause impairment of fertility.
• Footnote b added: For patients with unilateral renal tumor with predisposing conditions or bilateral renal tumors, a local stage III due to biopsy only may not need RT.

WILMS-H (2 of 3)

• Whole Lung Irradiation (WLI)
  • 1st bullet modified: Indications: WLI is recommended in patients with lung metastases and other extra-thoracic metastases (such as liver, bone, or brain), LN metastases in the hilum and/or mediastinum, or cytology-positivepleural effusion regardless of response to chemotherapy. Lung metastases. WLI can be delayed to week 6 in select patients with FHWT who only have metastases in the lungs and do not have 1q gain or combined LOH at both 1p and 16q.If WLI can be omitted if there is a CR to chemotherapy and the tumor did not have the unfavorable biomarkers, 1q gain or combined LOH at 1p and 16q. then WLI can be omitted.
  • 3rd bullet, 2nd bullet added: If possible, 4D imaging for motion assessment with creation of internal target volume (ITV) is recommended.
  • 4th bullet modified: If treating, or potentially treating, whole lung and abdomen/flank, consider planning the entire treatment up front. using one large field to avoid match lines.
• Radiation Doses
  • 1st bullet modified: Flank (10.8 Gyat 1.8 Gy per fraction) for local stage III
  • 2nd bullet modified: Whole abdomen (10.5 Gy at 1.5 Gy per fraction)
  • 3rd bullet modified: Whole lung (12 Gy at 1.5 Gy per fraction or 10.5 Gy at 1.5 Gy per fractionif <12 mo)
  • 4th bullet modified: LN irradiation. (10.8 Gy at 1.8 Gy per fraction) for resected LN metastases and focal boost (to19.8 Gy at 1.8 Gy per fraction)for unresected LN metastases.

WILMS-I (1 of 5)

• Heading Modified: Syndromes and Congenital Anomalies Associated with Wilms Tumor Principles of Cancer Risk Assessment and Counseling [Also WILMS-I (2 of 5), WILMS-I (3 of 5), WILMS-I (4 of 5), WILMS-I (5 of 5)]
• Page extensively revised.

WILMS-I (2 of 5)

• Page extensively revised.

WILMS-I (3 of 5)

• Page extensively revised.

WILMS-I (4 of 5)

• Page extensively revised.

 

 

 

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