Biological Drivers of Wilms Tumor Prognosis and Treatment
Abstract
:1. Introduction
2. Genomic and Molecular Alterations with Prognostic Significance in WT
2.1. Chromosome 11
2.2. Loss of Heterozygosity at 1p and 16q
2.3. Copy Number Gain at 1q
2.4. Alterations at 17p
2.5. Loss of Heterozygosity at 4q and 14q
2.6. MYCN Amplification
2.7. LOH at 11q
3. Current Risk Assignment and Treatment Strategies for Wilms Tumor
3.1. Very Low Risk
3.2. Low Risk
Stage I and II FHWT without LOH at 1p/16q
3.3. Standard Risk
3.3.1. Stage I and II FHWT with LOH at 1p/16q
3.3.2. Stage III FHWT without LOH at 1p/16q
3.3.3. Stage IV FHWT with Isolated Lung Metastases Responding Completely to Chemotherapy but without LOH at 1p/16q
3.4. Higher Risk
3.4.1. Stage III or IV FHWT with LOH 1p/16q
3.4.2. Stage IV FHWT without LOH at 1p/16q but with Isolated Lung Metastases Responding Incompletely to Chemotherapy
3.4.3. Stage IV FHWT with Extrapulmonary Metastases
3.5. High Risk
3.6. Bilateral, Multicentric, or Bilaterally-Predisposed Unilateral Wilms Tumor
3.6.1. Bilateral WT
3.6.2. Genetically Predisposed WT and Diffuse Hyperplastic Perilobar Nephroblastomatosis (DHPLN)
4. Conclusions
Funding
Conflicts of Interest
References
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Stage | Criteria |
---|---|
Stage I | Confined to kidney |
Complete excision with renal capsule intact and negative resection margins | |
Lymph nodes negative for Wilms tumor spread | |
Stage II | Regional extension beyond kidney capsule, but confined to flank |
May include: | |
Tumor penetration through capsule but confined to Gerota’s fascia | |
Infiltration into renal vein | |
Complete excision with negative resection margins | |
Lymph nodes negative for Wilms tumor spread | |
Stage III | Residual tumor, but confined to abdomen |
May include: | |
Regional lymph node involvement | |
Peritoneal contamination: | |
Biopsy | |
Pre- or intraoperative tumor rupture | |
Tumor growth through peritoneal surface | |
Positive resection margins | |
Stage IV | Distant metastases: Lung, liver, bone, brain |
Stage V | Involvement of bilateral kidneys at diagnosis |
Risk | Patient/Tumor Characteristics | Current Therapy | Results | Citation |
---|---|---|---|---|
Very low | Stage I FHWT | Nephrectomy only | 4-yr EFS: 89.7% (84.1–95.2%) | [48] |
Age <2 YO | 4-yr OS: 100% | |||
Tumor weight <550g | ||||
Low | Stage I or II FHWT − LOH 1p/16q | Nephrectomy Regimen EE-4A | 4-yr EFS: 91.2% (CI not provided) 4-yr OS: 98.4% (CI not provided) | [18] |
Standard | Stage I or II FHWT | Nephrectomy | 4-yr EFS: 83.9% (64.9–93.1%) | [49] |
+ LOH 1p/16q | Regimen DD-4A | 4-yr OS: Not published | ||
Stage III FHWT | Nephrectomy | 4-yr EFS: 88% (85–91%) | [50] | |
− LOH 1p/16q | Regimen DD-4A | 4-yr OS: 97% (95–99%) | ||
RT tumor bed + involved sites | ||||
Stage IV FHWT | Nephrectomy | 4-yr EFS: 79.5% (71.2–87.8%) | [51] | |
− LOH 1p/16q | Regimen DD-4A | 4-yr OS: 96.1% (92.1–100%) | ||
Isolated lung mets, RCR | RT tumor bed | |||
Higher | Stage IV FHWT | Nephrectomy | 4-yr EFS: 88.5% (81.8–95.3%) | [51] |
− LOH 1p/16q | Regimen M | 4-yr OS: 95.4% (90.9–99.8%) | ||
Isolated lung mets, SIR | RT tumor bed + involved sites | |||
Stage IV FHWT | Not published | |||
Extrapulmonary mets | ||||
Stage III or IV FHWT | 4-yr EFS: 91.5% (78.5–96.8%) | [49] | ||
+ LOH 1p/16q | 4-yr OS: Not published | |||
High | Any DAWT | Nephrectomy | 3-yr EFS: 69% (56–80%) | [52] |
Regimen UH-1 | 3-yr OS: Not published | |||
RT tumor bed + involved sites | ||||
Stage IV DAWT | Nephrectomy | 4-yr EFS: 57% (28–78%) | [52] | |
Irinotecan/Vincristine window | 4-yr OS: Not published | |||
Regimen UH-2 | ||||
RT tumor bed involved sites | ||||
Bilateral, Multicentric, Predisposed | Bilateral WT | Induction with Regimen VAD | 4-yr EFS: 82.1% (73.5–90.8%) | [53] |
(Partial) nephrectomy | 4-yr OS: 94.9% (90.1–99.7%) | |||
Adjuvant therapy depends on path | ||||
Unilateral tumors bilaterally predisposed | Induction with Regimen VA | Not published | ||
(Partial) nephrectomy | ||||
Adjuvant therapy depends on path | ||||
DHPLN | Regimen VA | Not published |
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Phelps, H.M.; Kaviany, S.; Borinstein, S.C.; Lovvorn, H.N., III. Biological Drivers of Wilms Tumor Prognosis and Treatment. Children 2018, 5, 145. https://doi.org/10.3390/children5110145
Phelps HM, Kaviany S, Borinstein SC, Lovvorn HN III. Biological Drivers of Wilms Tumor Prognosis and Treatment. Children. 2018; 5(11):145. https://doi.org/10.3390/children5110145
Chicago/Turabian StylePhelps, Hannah M., Saara Kaviany, Scott C. Borinstein, and Harold N. Lovvorn, III. 2018. "Biological Drivers of Wilms Tumor Prognosis and Treatment" Children 5, no. 11: 145. https://doi.org/10.3390/children5110145