Peter F Ehrlich1, Brett Tornwall2, Murali M Chintagumpala3, Yueh-Yun Chi2, Fredric A Hoffer4, Elizabeth J Perlman5, John A Kalapurakal6, Anne Warwick7, Robert C Shamberger8, Geetika Khanna9, Thomas E Hamilton8, Kenneth W Gow10, Arnold C Paulino11, Eric J Gratias12, Elizabeth A Mullen8, James I Geller13, Conrad V Fernandez14, Jeffrey S Dome14,15. 1. Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA. pehrlich@med.umich.edu. 2. Department of Biostatistics, University of Florida, Gainesville, FL, USA. 3. Texas Children's Hospital Cancer Center at Baylor College of Medicine, Houston, TX, USA. 4. Fred Hutchison Cancer Center, University of Washington, Seattle, WA, USA. 5. Ann & Robert H. Lurie Children's Hospital, Chicago, IL, USA. 6. Northwestern University, Chicago, IL, USA. 7. Walter Reed National Military Medical Center, Washington, DC, USA. 8. Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA, USA. 9. Washington University of St Louis, St Louis, MO, USA. 10. University of Washington, Seattle, WA, USA. 11. MD Anderson Cancer Center, Houston, TX, USA. 12. Children's Oncology Group, Philadelphia, PA, USA. 13. Cincinnati Children's Hospital, Cincinnati, OH, USA. 14. IWK Children's Hospital, Halifax, NS, Canada. 15. Children National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Abstract
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.
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.
Authors: Jesse K Sandberg; Yueh-Yun Chi; Ethan A Smith; Sabah Servaes; Fredric A Hoffer; Elizabeth A Mullen; Elizabeth J Perlman; Brett Tornwall; Peter F Ehrlich; James I Geller; Paul E Grundy; Conrad V Fernandez; Jeffrey S Dome; Geetika Khanna Journal: AJR Am J Roentgenol Date: 2020-03-11 Impact factor: 3.959
Authors: Robert C Shamberger; Gerald M Haase; Pedram Argani; Elizabeth J Perlman; Cecilia A Cotton; Janice Takashima; Daniel M Green; Michael L Ritchey Journal: J Pediatr Surg Date: 2006-04 Impact factor: 2.545
Authors: Peter Ehrlich; Yuen Y Chi; Murali M Chintagumpala; Fred A Hoffer; Elizabeth J Perlman; John A Kalapurakal; Ann Warwick; Robert C Shamberger; Geetika Khanna; Tom E Hamilton; Ken W Gow; Arnold C Paulino; Eric J Gratias; Elizabeth A Mullen; James I Geller; Paul E Grundy; Conrad V Fernandez; Michael L Ritchey; James S Dome Journal: Ann Surg Date: 2017-09 Impact factor: 12.969
Authors: R Furtwängler; M Schmolze; S Gräber; I Leuschner; G Amann; J-P Schenk; F Niggli; L Kager; D von Schweinitz; N Graf Journal: Klin Padiatr Date: 2014-05-12 Impact factor: 1.349
Authors: E A Eisenhauer; P Therasse; J Bogaerts; L H Schwartz; D Sargent; R Ford; J Dancey; S Arbuck; S Gwyther; M Mooney; L Rubinstein; L Shankar; L Dodd; R Kaplan; D Lacombe; J Verweij Journal: Eur J Cancer Date: 2009-01 Impact factor: 9.162