Protocol Summary National Wilms Tumor Study Group (NWTS) Patty Sponseller, CMD DOS741 Protocols and Studies in Radiation Oncology 2011

History Established 1969 Brought together investigators already participating in cooperative groups Founding Chairman, Dr. Guilio D’ Angio Vision cure childhood cancers, particularly Wilms tumor

History of NWTS Established in 1969 Original Institutions from Children’s Cancer Group and Pediatric Division of SWOG and CALBG In 2001 NWTSG and Intergroup Rhabdomyosarcoma Study Group to form new organization Children’s Oncology Group (COG) Patient entry in NWTSG ended in 2002 Subsequent and future trials for children with renal tumors are conducted by COG NWTS is still a destination used only for studying late effects of patients originally enrolled http://www.nwtsg.org

Combined Efforts Only 500 cases diagnosed annually Single or small groups of institutions not enough patients to study Investigators and Institutions agreed to combine efforts Goal was to get answers in a short period of time

Vision Survivors could lead normal adult lives Free of late effects caused by treatment NWTS pioneer in multi-modal treatment Included all professions as full members

Goals Improve survival Children with Wilms tumors or other renal tumors Study long-term outcomes Study epidemiology and biology of Wilms tumors Make this information available world wide

How would these children benefit? Investigators wanted answers to long standing therapy ?’s Determine risks Gauge outcomes Results – better treatment

NWTS Trials Conducted 5 trials Determine which drugs or combinations Decrease the radiation dose Enrolled more than 400 children/year 70% of Wilms Tumor patients in United States 33 year span

Control Each study identified objectives which included the original objectives New study built on results of previous study Resulted in improvements 1st trial already showed diminished late effects

NWTS-1 October 1969 to February 1975 Accrued 741 patients Results – No RT to low risk Group I Drug combinations more effective Favorable and unfavorable histologic classifications

NWTS-2 January 1975 to April 1979 Accrued 950 patients Results – Group I treated for 6 months ADR improved outcomes for Groups I & II Chemotherapy doses for babies Prognosis for favorable and unfavorable Grouping redefined and new staging

NWTS-3 May 1979 to September 1986 Accrued 2496 patients Results – Patients divided into 2 Groups Stage I FH or focal anaplasia no RT Stage III FH best with 3 drugs Stage III-IV 4 drugs

NWTS-4 August 1986 to August 1995 Accrued 3335 patients Results – “pulse intensive” drug doses Cost of therapy decreased

NWTS-5 August 1995 to May 2002 Accrued 3031 patients Results – Chromosomes tagged to outcome Surgery alone adequate Patients with pulmonary mets may benefit with doxorubicin

Results Radiotherapy Regiment Patients are treated on COG study Result of 5 trials dropped (FH) dose to abdomen to 1080 cGy and 1200 cGy whole lung Post-op RT start 14 days after surgery RT limited to Stages III and IV only Stage IV (FH) with pulmonary nodules after RT receive whole lung RT

Present Day Late effects study Includes only those enrolled in one of the original NWTS trials Determines risks and mortality rates Contributions to genetic epidemiology

Eligibility Participants must have been consented for one of the original trials Participant must have been registered All trial data was submitted to NWTS Tissue sent to central Pathology of NWTS Diagnosis Wilms, clear cell sarcoma of kidney or rhabdoid tumor of kidney

Success Answers to long standing ?’s in a short time frame Accomplished by a multi-modal group Careful data collection and follow up Research continues to lead to improvements Now carried out by COG