2.WILMS TUMOR - Mahidol University · Wilms Tumor Stage I, Favorable Histology NWTS-1 • Radiotherapy not necessary for Group 1 Wilms’ tumor < 2 years of age • There was a

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ROLE OF RADIOTHERAPY IN WILMS TUMOR

Arnold C. Paulino, M.D.Professor of Radiation Oncology

MD Anderson Cancer Center

Goals and Objectives

To gain an understanding of presentation and work-up of Wilms’ tumorTo determine the role of radiotherapy in localized and metastatic Wilms’ tumorTo gain familiarity with other pediatric renal tumors which may be treated with radiotherapy

Historical Background1814 Rance – first case (Case of fungus haematodes of the kidnies)1828 Gairdner –second case (Agnes B)1899 Max Wilms (Die Mischgeschwuelste)

Historical Background

Wilms’ tumor timeline

Incidence

450 cases/ year in the U.S.7 cases per million children in the U.S.Most common abdominal tumor of childhoodSex ratio 0.92:1(M:F)Median age: 3.5 years

Cases per million children

Epidemiology

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Congenital SyndromesSyndrome Presentation Chromosomal

LocusGenetic Change Incidence of

Wilms’ Tumor

WAGR Aniridia, genitourinary anomalies, mental retardation

11p13 Monoallelic deletion at chromosome 11p13

> 30%

Denys-Drash Intersexual disorders, nephropathy

11p13 WT1 point mutation

> 90%

Beckwith-Wiedemann

Macroglossia, organomegaly, neonatal hypoglycemia, gigantism

11p15 Duplication of paternal allele

< 5%

Breslow N et al. Med Pediatr Oncol 1993; 21:172-81

Aniridia

Incidence: 8.4 per 1000 Wilms tumor casesUsually identified prior to Wilms (median 522 days)Risk of developing Wilms ranges from 18% to 40%


HemihypertrophyIncidence: 24.7 per 1000 Wilms’ tumor casesMost commonly involves leg Hemihypertrophy diagnosed usually 1 day after dx of WilmsHemihypertrophy identified in only 32% of cases > 1 month prior to dx of Wilms

DeBaun MR, Tucker MA. J Pediatr 1998; 132:298-400

Beckwith-Wiedemann Syndrome

Relative risk for Wilms tumor during first 4 years of life: 816Also have a high incidence of hepatoblastoma, neuroblastoma, adrenocortical carcinoma


Genitourinary Abnormalities

Cryptorchidism 27.8*Hypospadias 17.8Double collecting system

15.2Fused kidney 3.7Other urinary 7.3Other genital 2.1

* per 1000 Wilms tumor cases

*Nicholson HS et al. Cancer 1996; 78:887-91.

Other Anomalies in Wilms Tumor Patients

Musculoskeletal system (clubfoot, hip anomalies)Uterine anomalies (septate uterus, unicornuate uterus)*Cardiovascular and Respiratory system (septal defects, accessory or anomalous renal vessels, coarctation of aorta)

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Molecular Biology

WT1 (germline deletion at 11p13)WT2 alteration at one or more loci on band 11p15 underlie development of BWS and Wilms’ tumorLOH 16q found in 20% of casesLOH 1p found in 10% of cases

Grundy P et al. Cancer Res 1994; 54:2331-3

LOH 16q

P = 0.01

Grundy P et al. Cancer Res 1994; 54:2331-3

LOH 1p

P = 0.08

LOH 1p and 16 q (Stage I/II FH, NWTS-5)

P = 0.01

Grundy PE et al. J Clin Oncol 2005; 23:7312-21

LOH 1p and 16 q (Stage III/IV FH), NWTS-5

P = 0.04


Clinical Presentation

Abdominal Mass (in an otherwise healthy child)Abdominal PainHematuriaHypertensionMalaiseVaricocoele

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Work-Up of Abdominal Mass

HistoryPhysical ExaminationAbdominal UltrasoundCBCLiver function , BUN, creatinineUrine catecholamines

NWTS-5 Pretreatment Evaluation

Work-up of Wilms’ tumor

Computed tomography of abdomen and pelvisComputed tomography of chestSkeletal survey (CCSK only)Radionuclide bone scan (CCSK only)MRI of brain (CCSK and Rhabdoid tumor)Bone marrow aspiration and biopsy (CCSK only)

Computed tomography of abdomen Differential Diagnosis

Pathology Favorable Histology

StromalEpithelialBlastemal

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Relapses after Preoperative Chemotherapy According to Pathology (SIOP-9/GPOH)

Histologic Subtype

Stage I (%) Stage II (%) Stage IIN+/III(%)

Total (%)

Epithelial predominant

0/7 (0) 0/1 (0) - 0/8 (0)

Stromal predominant

0/25 (0) 0/8 (0) 0/3 (0) 0/36 (0)

Blastemal predominant

5/11 (45.4) 2/8 (25.0) 2/5 (40.0) 9/24 (37.5)

Mixed 5/54 (9.3) 3/16 (18.8) 0/6 (0) 8/76 (10.5)Regressive-

change predominant

4/52 (7.7) 1/22 (4.5) 5/23 (21.7) 10/97 (10.3)

Completely necrotic

0/9 (0) 0/5 (0) 0/3 (0) 0/17 (0)

Weirich A et al. Ann Oncol 2001; 12:311-9

North American Approach

North AmericaImmediate nephrectomyChemotherapy +/-Radiotherapy Depending on Stage and histology

European Approach

Preoperative chemotherapy followed by nephrectomyAdditional chemotherapy +/-radiotherapy according to stage and histology

NORTH AMERICAN(POSTOPERATIVE)

EUROPEAN(PREOPERATIVE)

Diagnosis and stage known Decrease Tumor Rupture/SpillageLess Children Receiving Radiotherapy

Staging System for Wilms’ TumorI Tumor confined to kidney and completely resected. No

penetration of the renal capsule or involvement of renal sinus vessels

II Tumor extends beyond kidney but completely resected. (a) penetration of renal capsule (b) invasion of renal sinus vessels

III Gross or microscopic residual remains postoperatively (inoperable tumor, positive surgical margins, tumor spillage either before or during surgery, regional lymph node metastases, tumor is removed greater than one piece, penetration through peritoneal surface)

IV Hematogenous or lymph node metastases outside abdomenV Bilateral Wilms’ tumor at onset

Stage Distribution

43%

20%

21%

11%5%

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Wilms Tumor Stage I, Favorable Histology

NWTS-1• Radiotherapy not necessary for Group 1 Wilms’ tumor < 2

years of age• There was a benefit for radiotherapy for Group 1 Wilms’

tumor > 2 years of age (2 yr DFS: 77% vs. 58%, p = 0.04). These pts were treated with Regimen A (AMD alone)

NWTS-2• Radiotherapy not used in Group I patients. VCR was added

to regimen. Randomization was 6 mos vs. 15 mos. Of AMD + VCR. 3-yr RFS was 89% and 84% respectively

D'Angio GJ et al. Cancer 1976, D'Angio et al. Cancer 1981

Wilms Tumor Stage II, Favorable Histology

NWTS-3 Treatment Percent alive at 2 years

AMD + VCR 98.6%

AMD + VCR + 2000 cGy 98.4%

AMD + VCR + ADR 95.5%

AMD + VCR + ADR + 2000 cGy 93.5%

D'Angio GJ et al. Cancer 1989; 64:349-60

Wilms Tumor Stage III, Favorable Histology

NWTS-3 Treatment Percent alive at 2 years

AMD + VCR + 1000 cGy 88.3%

AMD + VCR + 2000 cGy 91.0%

AMD + VCR + ADR + 1000 cGy 92.7%

AMD + VCR + ADR + 2000 cGy 93.1%

D'Angio GJ et al. Cancer 1989; 64:349-60

Shamberger RC et al. Ann Surg 1999; 229:292-7

Spill and Local Recurrence: The Case for Radiation Therapy

Stage II Stage III

No Spill RR = 1.0 RR = 1.0

Spill RR = 4.5 RR = 1.9

SIOP-1, -5 and Tumor Rupture

In SIOP-1, tumor rupture occurred in 32% of patients who had primary surgery (n =63) and in 4% who had 20 Gy preoperative RT (n=73) (p = 0.001)In SIOP-5, tumor rupture was 6% with preoperative VCR + AMD chemotherapy (n =88) and 8% with 20 Gy preoperative RT (n=76) (p=n.s.)

Lemerle J et al. J Clin Oncol 1983; 1:604-9

Intraoperative Spill

135/1131 (11.9%) of unilateral Wilms tumor on AREN03B2 had intraoperative spillage of tumor110 were secondary to the primary tumor while 20 occurred due to renal vein thrombectomyTwo factors associated with intraoperative spill: tumor size > 12 cm and right laterality

Gow KW et al. J Pediatr Surg 2013; 48:34-8

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Tefft M et al. Int J Radiat Oncol Biol Phys 1980; 6:663-7

Local Recurrence Risk Factors (NWTS-1)

Delay Favorable Histology

Unfavorable Histology

P-value

< 10 days 13/220 (6%) 2/29 (7%) 0.25

> 10 days 2/53 (4%) 6/15 (40%) 0.001

Thomas PRM et al. J Clin Oncol 1984; 2:1098-101

Local Recurrence Risk Factors (NWTS-2)

Factor Intraabdominal Relapse

No Intraabdominal

Relapse

P-value

Unfavorable histology

6/10 (60%) 25/249 (10%) 0.001

Field size too small

4/10 (40%) 17/249 (59%) 0.004

Delay > 10 days from surgery

8/10 (80%) 91/249 (37%) 0.005

RT Treatment Delay

Final pathology and stage needed within a few days to determine if child needs RTNeed time to do simulationYounger children may need anesthesiaSimulating all children with renal masses seem to be inappropriate

Kalapurakal JA et al. Int J Radiat Oncol Biol Phys 2003; 57:495-9

RT Treatment Delay (NWTS-3 & 4)

Total of 1226 children with Stage II-IV FH children received flank or abdominal RTMean RT delay: 10.9 days (median: 9 days)59% had RT delay between 8 to 12 days8-year flank/abdominal recurrence rates were 1.9/4.8% for delay < 10 days and 1.2/5.3% for delay > 10 days (p = n.s.)

Pulmonary Lesions and RT

Chest X-ray has traditionally been used to stage patientsCT scan better in detecting nodulesNot all nodules are metastatic Wilms’ tumor although lungs are most common site of metastasis

DIFFERENTIAL DIAGNOSIS

Wilms’ tumor metastasisAtelectasisRound pneumoniaIntrapulmonary Lymph NodeHistoplasma capsulatumHamartomaPseudotumor

Wilimas JA et al. J Clin Oncol 1988; 6:1144-6

St. Jude Study (+ lung mets on CT only)

11/124 (9%) of Wilms’ tumor pts had negative CXR and positive chest CTTreated according to local stage (I.e. no lung RT)4/11 (36%) relapsed – all pulmonary

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Wilimas JA et al. J Clin Oncol 1997; 15:2631-5

Interobserver Variability

CT scan

Reviewer 1 Reviewer 2 Reviewer 3

CXR Present Absent Present Absent Present Absent

Present 3 10 7 4 2 4

Absent 33 153 55 118 22 158

Green DM et al. J Clin Oncol 1991; 9:1776-81

NWTS-3 (+ lung mets on CT only)

Relapses Deaths

N N(r) % RFS N (d) % Survival

Lung RT 18 2 88.1 1 94.0

No RT 9 1 88.9 1 88.0

P = .95 P = .63

Meisel JA et al. Int J Radiat Oncol Biol Phys 1999; 44:579-85

NWTS-3 and –4 Update

N N (relapsed)

4-yr EFS

N (died)

4-yr OS

RT 53 7 89% 6 91%

No RT 37 7 80% 5 85%P =.23 P=.41

UKW2 Study (No Lung XRT)

31/141 children (22%) had positive CT but negative CXR

Owens CM et al. J Clin Oncol 2002; 20:2768-73

Pulmonary Relapse

CT positive 4/31 (13%)

CT negative 8/110 (7.3%)

p = n.s.

UKW2 Study (No Lung XRT)

Owens CM et al. J Clin Oncol 2002; 20:2768-73

Pulmonary Relapse

CT positive 3/7 (43%)

CT negative 5/48 (10%)P = 0.02

Stage I, N = 55

Stage I pts. treated with VCR chemo only

Lung Mets (NWTS-4 and -5)

All favorable histology without other sites of distant metastasis417 pts (NWTS-4 with 165 and NWTS-5 with 252 pts)

Lung Mets at Diagnosis

Chest X ray positive CT only P-value

Male (%) 36.8 39.2 0.68

Age at dx (mos) 61.6 54.2 0.02

Tumor weight (grams) 610.6 678.8 0.12

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CT Only Lung Mets (NWTS-4 and -5)

Chemotherapy No. of pts 2 yearRFS (%)

5 year RFS (%) P-value

Actinomycin-D and Vincristine 39 58.1 54.4

0.01Actinomycin-DVincristine and Doxorubicin

145 84.2 79.7

Radiotherapy No. of pts 2 yearRFS (%)

5 year RFS (%) P-value

Whole Lung Radiotherapy 67 89.0 84.6

0.38No Whole Lung Radiotherapy 91 73.2 69.6

SIOP Study

36 children with Stage IV Wilms’ tumor and pulmonary metastasisAll diagnosed by chest radiograph. CT scan of chest not requiredReceived 6 weeks of preoperative AMD (1.5 micrograms/kg), VCR (1.5 mg/m2) and ADR (50 mg/m2)

SIOP Study

de Kraker J et al. J Clin Oncol 1990; 8:1187-90

SIOP Study

Maintenance chemo (5 courses of AMD and VCR)26 of 36 children did not receive pulmonary RT5-year recurrence-free survival: 83%

Current COG Guidelines

Pulmonary XRT (1200 cGy in 8 fractions) at 6 weeks post chemotherapy can be omitted if all are satisfiedComplete response in lungs after 3-drug chemotherapyNo LOH 1p AND 16qNo extrapulmonary metastasisFavorable histology

AREN0533 Lung Metastasis

From Feb. 2007 to 2013, 391 Stage IV FH pts enrolled of which 279 had isolated lung mets163 of 279 (58%) did not achieve pulmonary CR and received WLI and Regimen M3-year EFS and OS were 88% and 92% (compared to historical standard, p =0.0001)

Dix DB et al J Clin Oncol 32:5s, 2014 (suppl; abstr 10001)

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Larsen E et al. Cancer 1990; 66:264-6

No Adjuvant Therapy

Dana Farber Cancer Institute/Children’s Hospital Boston pilot studyCassady tumor (age < 24 months with Stage I, unilateral, small (total tumor/kidney weight < 550 g), FH)N = 8, 5-year survival without adjuvant chemotherapy 100%, 5-year event-free survival 88%

Green DM et al. J Clin Oncol 2001; 19:3719-24

NWTS-5 No Adjuvant Therapy

75 children < 24 mos with Stage I FH, < 550 g Wilms’ tumor treated with nephrectomy alone3 children developed a metachronous tumor 1.1-2.3 yrs and 8 relapsed at 0.3-1.05 years after diagnosisRelapse at lung (n=5), abdomen (n=3)2-year survival: 100%, disease-free survival 86.5%

Survival for Favorable Histology Wilms’ Tumor

Relapse-Free

Survival

Overall Survival

Stage I, FH 92% 98%Stage II, FH 85% 96%Stage III, FH 90% 95%Stage IV, FH 80% 90%Stage V, FH 65% 78%

NCI PDQ Summary

Current COG GuidelinesStage Chemotherapy Radiotherapy

Stage I, FH, age < 2 years with tumor and kidney weight < 550 grams

None None

Stage I and II, FH with no LOH 1p and 16q

VCR and AMD(Regimen EE4A)

None

Stage I and II, FH with LOH at 1p and16q

VCR, AMD and DOX(regimen DD4A)

None

Stage III, FH with no LOH at 1p and 16q VCR, AMD and DOX (Regimen DD4A)

Abdominal/Flank RT

Stage III, FH with LOH at 1p and 16q VCR, AMD, DOX, CPM, VP16 (Regimen M)

Abdominal/Flank RT

Stage IV, FH with no LOH at 1p and 16q VCR, AMD and DOX(Regimen DD4A)

Abdominal/Flank RT if Local Stage IIILung XRT if Lung Mets not CR

Stage IV, FH with LOH at 1p and 16q VCR, AMD, DOX, CPM, VP-16 (RegimenM)

Abdominal/Flank RT if Local Stage IIILung XRT if Lung Mets

COG RT Guidelines for FH Wilms’ Tumor

Disease Extent RT Volume Dose

Hilar lymph nodes/Gross or microscopic residual confined to flank/ Local spill

Tumor bed, crossing midline to include entire vertebral bodies

1080 cGy/ 6 fx

Para-aortic lymph nodes Include bilateral para-aortic chains

1080 cGy/ 6 fx

Peritoneal seeding, Preoperative peritoneal rupture, Diffuse operative spill

Whole abdomen 1050 cGy/ 7 fx

COG RT Guidelines for MetastasisDisease site RT Field RT Dose

Liver Involved portion + 2 cm margin

1980 cGy/11 fx

Lung, age > 18mos Bilateral lung 1200 cGy/8 fx

Lung, age < 18 mos Bilateral lung if no response to chemo

900 cGy/ 6 fx

Lymph nodes (Gross tumor, not resected)

Involved nodes 1980 cGy/ 11 fx

Brain Whole brain +/- boost 2160 cGy/ 17 fx (WB)1080 cGy/6 fx (boost) if < 16 yrs3060 cGy/ 17 fx (WB, if > 16 yrs)

Bone Lesion + 3 cm margin 2520 cGy/14 fx (< 16 yrs)3060 cGy/17 fx (> 16 yrs)

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Radiotherapy Fields (Stage IV)3 year old girl with focal anaplastic Wilms’ tumor of right kidney with microscopic margin, positive paraaortic node and pulmonary metastasis1050 cGy in 7 fractions to R hemiabdomen and 1200 cGy in 8 fractions to bilateral lungs

Radiotherapy Fields (Stage IV)2 year old boy with favorable histology Wilms’ tumor of R kidney (capsular penetration only) and pulmonary metastasesHad residual pulmonary mets after 6 weeks of chemotherapy1200 cGy in 8 fractions to bilateral lungs

Radiotherapy Fields (Stage III)

4 year old female with favorable histology Wilms’ tumor and diffuse spillage of tumor during left nephrectomy. Three positive paraaotic lymph nodes with negative margin of resectionPatient received 1050 cGy in 7 fractions to the whole abdomen

Bilateral Wilms’ Tumor

Synchronous Metachronous

NWTS-1 33/606 (5.4%) 20/606 (3.3%)

NWTS-2 and 3 145/3300 (4.4%)

St. Jude 29/328 (8.8%) 7/328 (2.1%)

SIOP 1, 2, 5 42/1043 (4.0%) 25/1043 (2.4%)

Synchronous Bilateral Wilms’ Tumor

SURVIVAL

2 years 5 years 10 years

NWTS-2 and –3Montgomery BT et al. J Urol 1991; 146:514-8

83% 73% 70%

SIOP 1,2,5Coppes MJ et al. J Clin Oncol 1989; 7:310-5

NA NA 69%

St. JudePaulino AC et al. Int J Radiat Oncol Biol Phys 1996; 36:541-8

81% 74% NA

Synchronous Bilateral Wilms’ Tumor

Chemotherapy (AMD, VCR, DOX)

Partial Nephrectomy

Chemotherapy +/- Radiotherapy(XRT given to positive margin, positive lymph node, unfavorable histology)

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Paulino AC et al. Cancer 1998; 82:415-20

Metachronous Bilateral Wilms’ Tumor

Review of 108 cases from 30 studies from 1950-19965- and 10-year overall survivals were 49.1% and 47.2%More than 95% of contralateral tumors occur within 60 months (median 23.1 months)Better survival with contralateral tumors appearing > 18 months from initial ipsilateral tumor (10 yr survival 55.2% vs. 39.6%)

Relapsed Wilms’ TumorN Survival

3 years 5 years

Grundy et al.NWTS-2 and -3

367 30% NA

Dome et al.St. Jude Children’s Hospital

54 NA 21% (prior to 1984)64% (after 1984)

Groot-Loonen et al.UKCCSG WT-1 Study

71 24% NA

Paulino et al.University of Iowa

21 38% 33%

Tannous et al.CCG-4921/POG-9945 HRisk

66 52% NA

Kaplan-Meier curves for (A) event-free and (B) overall survival for local stage III favorable-histology Wilms tumor by microscopic disease, nonmetastatic only.

Ehrlich P F et al. JCO 2013;31:1196-1201

Predictors of Relapse in Stage III FH Wilms Tumor

Grundy P et al. J Clin Oncol 1989; 7:638-47

Relapsed Wilms (3-yr post-RFS > 40%)

Favorable histology tumors with relapse1. Only in lungs2. In abdomen when RT not used3. Originally Stage I4. Treated with only 2 drugs5. Recurred 12 or more months after initial

diagnosis


Patterns of Failure: NWTS-2 and 3

Site Frequency

Lung only 58%

Abdomen +/- lung 29%

Other 13%

Anaplastic Wilms’ Tumor

Unfavorable histology found in 4 to 5% of NWTS and SIOP studiesUncommon in infants, but found in about 10% of patients > 5 years of ageAnaplasia refers to significant enlargement of nuclei in stromal, blastemal or epithelial components to at least 3X, hyperchromatism of enlarged nuclei and multiple mitotic figures

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Faria P et al. Am J Surg Pathol 1996; 20:909-20


Faria P et al. Am J Surg Pathol 1996; 20:909-20


In NWTS-4, Stage I AH pts were treated with AMD and VCR and had 2-yr overall survival estimates of 85.5% to 93.3% depending on AMD administration regimenStage II to IV AH pts were treated with AMD, VCR and DOX and had 4-yr overall survival rate of 27.1% without CPM and 52.2% with CPM (p = 0.04)

Anaplastic Wilms’ Tumor (NWTS-5)

Dome JS et al. J Clin Oncol 2006; 24:2352-8

Anaplastic Wilms’ Tumor (NWTS-5)

Dome JS et al. J Clin Oncol 2006; 24:2352-8

Stage I4-yr EFS: 69.5%4-yr OS: 82.6%

4-yr EFS/OSStage II: 82.6%Stage III: 64.7%Stage IV: 33.3%

p=0.56, Green DM et al. J Clin Oncol 1994; 12:2126-31

RT Dose in Anaplastic Wilms’ Tumor

Dose (Gy) N No. of Tumor Bed Relapses

4-Year Tumor Bed Relapse-free Survival

(%)0 – 18.0 8 1 85.7

18.01-21.6 8 0 100.0

21.61-27.0 4 1 50.0

27.01-32.4 11 1 90.0

32.41-37.8 28 2 89.5

> 37.8 7 0 100.0

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Survival for Anaplastic Wilms’ Tumor

Relapse-Free Survival

Overall Survival

Stage I, FA/DA 69% 83%

Stage II, FA 80% 80%

Stage II, DA 83% 82%

Stage III, FA 71-88% 71-100%

Stage III, DA 46-65% 53-67%

Stage IV, FA 61% 72%

Stage IV, DA 31-33% 33-44%

Stage V, FA/DA 44% 55%

NCI PDQ SummaryArgani P et al. Am J Surg Pathol

2000; 24:4-18

Clear Cell Sarcoma of Kidney

First reported by Kidd in 197020 cases each year in the US (4-5% of all renal tumors)2:1 M:F ratio29% lymph node mets at presentationMost common site of recurrence is bone and lung, followed by abdomen and brain

Clear Cell Sarcoma (NWTS-4)

Seibel NL et al. J Clin Oncol 2004; 22:468-73

Clear cell Sarcoma of Kidney

N 8-yr RFS

8-yr OS

NWTS-4 86 71.6% 83.0%NWTS-3 90 60.2% 66.9%

Seibel NL et al. J Clin Oncol 2004; 22:468-73

p=0.56, Green DM et al. J Clin Oncol 1994; 12:2132-7

RT Dose in Clear Cell Sarcoma

Dose (Gy) N No. of Tumor Bed Relapses

4-Year Tumor Bed Relapse-free Survival (%)

0 – 18.0 16 0 100.018.01-21.6 18 2 85.921.61-27.0 21 0 100.027.01-32.4 21 0 100.032.41-37.8 15 1 91.7> 37.8 8 1 83.3

Rhabdoid Tumor

2% of all renal tumors80% < 2 years old1.5:1 M:F ratioCharacterized by INI-1 gene mutationAssociation with primary intracranial mass or brain metastasisWorst prognosis for renal tumors

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Rhabdoid Tumor

Tomlinson GE et al. J Clin Oncol 2005; 23:7641-5

*Mitchell C et al. Br J Cancer 2000; 83:602-8

RT Dose in Rhabdoid Tumor

In NWTS-5, children received 10.8 GyMany of these children are infants In the UKCCSG Second Wilms’ tumor study, dose used was 30 Gy with vincristine, actinomycin and doxorubicin2-and 4-year EFS (UKCCSG) was 36%*Optimal dose not known

Rhabdoid Tumor

Tomlinson GE et al. J Clin Oncol 2005; 23:7641-5

Current COG GuidelinesStage Chemotherapy Radiotherapy

Stage I-III, FAStage I, DA

VCR, AMD and DOX(Regimen DD4A)

Abdominal/Flank RT

Stage IV, FAStage II-IV, DA (with no measurable disease)Stage IV, CCSKStage I-IV, RTK

VCR,AMD, DOX, CPM, VP16, CARBO(Regimen UH-1)

Abdominal/Flank RTLung RT if lung mets

Stage IV, DA (with measurable disease)

VCR, AMD, DOX, CPM, VP16, CARBO, IRINOTECAN

Abdominal/Flank RTLung RT if lung mets

Stage I-III CCSK VCR, AMD, DOX, CPM, VP16 (Regimen I)

Abdominal/Flank RT except Stage I CCSK

Current COG Guidelines

Stage Radiotherapy Dose

Stage I, CCSK No RTStage I-III, FAStage I-II, DAStage II-III, CCSKRTK, < 1 year old

10.8 Gy in 6 fractionsAbdominal/Flank RT

Stage III DARTK, > 1 year old

19.8 Gy in 11 fractionsAbdominal/Flank RT

FA, DA, CCSK, RTK 12 Gy in 8 fractionsLung Mets

ConclusionsCurrent survival rates for most children with Wilms’ tumor are excellentSuccessive trials have reduced the number of children who will require radiotherapy for Wilms’ tumorTumors with LOH 1p AND 16q have a worse prognosis and are currently being treated with more aggressive therapy

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Conclusions

It is unclear whether whole lung irradiation improves outcome in the setting of CT positive only disease

Documents

2.WILMS TUMOR - Mahidol University · Wilms Tumor Stage I, Favorable Histology NWTS-1 • Radiotherapy not necessary for Group 1 Wilms’ tumor < 2 years of age • There was a