TY - JOUR
T1 - Kidney Preservation and Wilms Tumor Development in Children with Diffuse Hyperplastic Perilobar Nephroblastomatosis
T2 - A Report from the Children’s Oncology Group Study AREN0534
AU - Ehrlich, Peter F.
AU - Tornwall, Brett
AU - Chintagumpala, Murali M.
AU - Chi, Yueh Yun
AU - Hoffer, Fredric A.
AU - Perlman, Elizabeth J.
AU - Kalapurakal, John A.
AU - Warwick, Anne
AU - Shamberger, Robert C.
AU - Khanna, Geetika
AU - Hamilton, Thomas E.
AU - Gow, Kenneth W.
AU - Paulino, Arnold C.
AU - Gratias, Eric J.
AU - Mullen, Elizabeth A.
AU - Geller, James I.
AU - Fernandez, Conrad V.
AU - Dome, Jeffrey S.
N1 - Funding Information:
This project was supported by the Chair's Grant (U10CA098543), National Clinical Trials Network (NCTN) Group Operations Center Grant (U10CA180886), Statistics and Data Center Grant (U10CA098413), NCTN Statistics and Data Center Grant (U10CA180899), and Human Specimen Banking in NCI-Sponsored Clinical Trials (U24CA114766 and 1U24-CA196173), and supported by St. Baldrick’s Foundation. Statistics & amp; Data Center Grant, U10CA098413, Human Specimen Banking in NCI-Sponsored Clinical Trials,1U24-CA196173, Human Specimen Banking in NCI-Sponsored Clinical Trials, U24CA114766, NCTN Statistics & Data Center, U10CA180899, Chair's Grant, U10CA098543, NCTN Network Group Operations Center Grant, U10CA180886
Publisher Copyright:
© 2022, Society of Surgical Oncology.
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Child, Preschool
KW - Dactinomycin/therapeutic use
KW - Female
KW - Humans
KW - Infant
KW - Kidney/pathology
KW - Kidney Neoplasms/drug therapy
KW - Male
KW - Nephrectomy
KW - Precancerous Conditions/pathology
KW - Wilms Tumor/drug therapy
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U2 - 10.1245/s10434-021-11266-6
DO - 10.1245/s10434-021-11266-6
M3 - Article
C2 - 35072864
AN - SCOPUS:85123477082
SN - 1068-9265
VL - 29
SP - 3252
EP - 3261
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 5
ER -