Surgery As Monotherapy for Wilms’ Tumor Lisly Chéry April 15, 2010

TL 15 month old male 15 month old male PMHx PMHx Failure to thrive / small stature Failure to thrive / small stature Developmental delay Developmental delay PSHx PSHx Hypospadias repair Hypospadias repair ROS negative ROS negative

TL Physical Exam Physical Exam Found to be hypertensive to 140s/90s Found to be hypertensive to 140s/90s

TL Physical Exam Physical Exam Found to be hypertensive to 140s/90s Found to be hypertensive to 140s/90s Left abdominal / flank mass Left abdominal / flank mass

TL Physical Exam Physical Exam Found to be hypertensive to 140s/90s Found to be hypertensive to 140s/90s Left abdominal / flank mass Left abdominal / flank mass Work-up Work-up Lab work Lab work

TL Physical Exam Physical Exam Found to be hypertensive to 140s/90s Found to be hypertensive to 140s/90s Left abdominal / flank mass Left abdominal / flank mass Work-up Work-up Lab work Lab work Cr 0.3 / Alb 3.7L / Hct 31L / Plts 281 / WBC 11.5 Cr 0.3 / Alb 3.7L / Hct 31L / Plts 281 / WBC 11.5 PT 12.8 / PTT 30 / INR 1.0 PT 12.8 / PTT 30 / INR 1.0

TL Physical Exam Physical Exam Found to be hypertensive to 140s/90s Found to be hypertensive to 140s/90s Left abdominal / flank mass Left abdominal / flank mass Work-up Work-up Lab work Lab work Cr 0.3 / Alb 3.7L / Hct 31L / Plts 281 / WBC 11.5 Cr 0.3 / Alb 3.7L / Hct 31L / Plts 281 / WBC 11.5 PT 12.8 / PTT 30 / INR 1.0 PT 12.8 / PTT 30 / INR 1.0 Imaging Imaging

TL Treatment Treatment Exploratory laparotomy Exploratory laparotomy Left nephrectomy Left nephrectomy Aortic lymph node dissection Aortic lymph node dissection

TL Returned to floor post-op Returned to floor post-op Nephrology consult for hypertension Nephrology consult for hypertension Normal right renal artery on US Normal right renal artery on US Discharged home on POD 4 Discharged home on POD 4 Tylenol Tylenol Oxycodone Oxycodone Amlodipine Amlodipine

TL Pathology report Pathology report Cystic Wilms’ tumor, favorable histology Cystic Wilms’ tumor, favorable histology Renal capsule intact, margin negative Renal capsule intact, margin negative Renal sinus uninvolved Renal sinus uninvolved Renal vein uninvolved Renal vein uninvolved 0 of 8 lymph nodes involved 0 of 8 lymph nodes involved 387 grams 387 grams

Staging Stage I – confined to kidney, complete resection, no rupture, no residual tumor Stage I – confined to kidney, complete resection, no rupture, no residual tumor Stage II – extra-renal disease, compete resection Stage II – extra-renal disease, compete resection Stage III – residual tumor [incomplete resection, positive margins, spillage, rupture, biopsy, lymph node involvement] Stage III – residual tumor [incomplete resection, positive margins, spillage, rupture, biopsy, lymph node involvement] Stage IV – distant metastasis [lung, liver, bone, brain] Stage IV – distant metastasis [lung, liver, bone, brain] Stage V – bilateral disease on presentation Stage V – bilateral disease on presentation

Staging Stage I – confined to kidney, complete resection, no rupture, no residual tumor Stage I – confined to kidney, complete resection, no rupture, no residual tumor Stage II – extra-renal disease, compete resection Stage II – extra-renal disease, compete resection Stage III – residual tumor [incomplete resection, positive margins, spillage, rupture, biopsy, lymph node involvement] Stage III – residual tumor [incomplete resection, positive margins, spillage, rupture, biopsy, lymph node involvement] Stage IV – distant metastasis [lung, liver, bone, brain] Stage IV – distant metastasis [lung, liver, bone, brain] Stage V – bilateral disease on presentation Stage V – bilateral disease on presentation

Very Low Risk Wilms’ Tumor Children less than 24 months at diagnosis Children less than 24 months at diagnosis Favorable histology on final pathology Favorable histology on final pathology Specimen < 550 grams Specimen < 550 grams

Founded in 1969 Founded in 1969 NWTS-1 and NWTS-2 – combined chemotherapy regimens NWTS-1 and NWTS-2 – combined chemotherapy regimens NWTS-3 – appropriate use of XRT NWTS-3 – appropriate use of XRT NWTS-4 – chemotherapy dosing and duration NWTS-4 – chemotherapy dosing and duration NWTS-5 – biological prognostic factors NWTS-5 – biological prognostic factors National Wilms’ Tumor Study Group

NWTS-3 / Case-control NWTS-3 / Case-control 24 relapses of stage I FH Wilms’ Tumor 24 relapses of stage I FH Wilms’ Tumor Associated factors = Microsubstaging Variables Associated factors = Microsubstaging Variables Inflammatory pseudocapsule Inflammatory pseudocapsule Renal sinus invasion Renal sinus invasion Invasion of tumor capsule Invasion of tumor capsule Tumor in intra-renal vessels Tumor in intra-renal vessels

NWTS-4 / retrospective cohort study NWTS-4 / retrospective cohort study 473 patients – Stage I FH 473 patients – Stage I FH 2 tailed Fisher’s exact test 2 tailed Fisher’s exact test Less likely to have positive microsubstaging variables Less likely to have positive microsubstaging variables Age < 2 years Age < 2 years Specimen weight < 550 grams Specimen weight < 550 grams

Small prospective trial Small prospective trial 8 patients, age < 2 years, favorable histology, Unilateral tumor, <550 grams 8 patients, age < 2 years, favorable histology, Unilateral tumor, <550 grams Relapse-free survival 88% Relapse-free survival 88% 1 metasynchronously occurring bilateral tumor 1 metasynchronously occurring bilateral tumor Overall survival 100% Overall survival 100%

NWTS-5 / prospective cohort study NWTS-5 / prospective cohort study 75 patients 75 patients Stage I FH, < age 2, < 550 grams Stage I FH, < age 2, < 550 grams 11 events 11 events 5 lungs relapses 5 lungs relapses 3 operative bed relapses 3 operative bed relapses 3 contralateral kidney 3 contralateral kidney Stopped after 3 years due to relapse-free survival < 90% Stopped after 3 years due to relapse-free survival < 90%

77 surgery only 77 surgery only 111 surgery and chemotherapy 111 surgery and chemotherapy Event free survival Event free survival 84% surgery only 84% surgery only 97% surgery and chemotherapy 97% surgery and chemotherapy Overall survival Overall survival 98% surgery only 98% surgery only 99% surgery and chemotherapy 99% surgery and chemotherapy

Future Histological identification Histological identification Genetic identification Genetic identification

TL Surgery only or adjuvant chemotherapy? Surgery only or adjuvant chemotherapy?

References D’Angio, Giulio. Pediatric oncology refracted through the prism of wilms’ tumor: a discourse. J Urol Dec;164(6): Ritchey et al. Surgical complications after nephrectomy for Wilms' tumor. Surg Gynecol Obstet Dec;175(6): D’Angio, Giulio. The National Wilms’ Tumor Study: a 40 year perspective. Lifetime Data Anal (2007) 13:463–470 Weeks et al. Relapse-associated variables in stage I favorable histology Wilms' tumor. A report of the National Wilms' Tumor Study. Cancer Sep 15;60(6): Green et al. The relationship between microsubstaging variables, age at diagnosis, and tumor weight of children with stage I/favorable histology Wilms' tumor. A report from the National Wilms' Tumor study. Cancer Sep 15;74(6): Larsen et al. Surgery only for the treatment of patients with stage I (Cassady) Wilms' tumor. Cancer Jul 15;66(2): Green et al. Treatment with nephrectomy only for small, stage I/favorable histology Wilms' tumor: a report from the National Wilms' Tumor Study Group. J Clin Oncol Sep 1;19(17): Shamberger et al. Long-term outcomes for infants with very low risk Wilms’ tumor treated with surgery alone in National Wilms’ Tumor Study-5. Ann Surg Mar;251(3):555-8.