wilms’ tumor – indications for radiotherapy tasha mcdonald m.d. parag sanghvi m.d. department of...

Wilms’ Tumor – Wilms’ Tumor – Indications for Indications for RadiotherapyRadiotherapy

Tasha McDonald M.D. Tasha McDonald M.D.

Parag Sanghvi M.D. Parag Sanghvi M.D.

Department of Radiation Department of Radiation MedicineMedicine

TreatmentTreatment

Based on cooperative group Based on cooperative group philosophiesphilosophies

3 major groups3 major groups National Wilm’s Tumor Study (NWTS)National Wilm’s Tumor Study (NWTS) Societe Internationale d’Oncologie Societe Internationale d’Oncologie

Pediatrique (SIOP)Pediatrique (SIOP) United Kingdom Children’s Cancer United Kingdom Children’s Cancer

Study Group (UKCCSG)Study Group (UKCCSG)

NWTS StrategyNWTS Strategy

Assess local extent, degree of Assess local extent, degree of anaplasia, presence of unusual anaplasia, presence of unusual histology, presence of LN histology, presence of LN involvementinvolvement

Assess without preoperative Assess without preoperative treatmenttreatment Gather prognostic cluesGather prognostic clues Avoid misdiagnosisAvoid misdiagnosis Customize therapyCustomize therapy

NWTS 1 – 4 SchemaNWTS 1 – 4 Schema

NWTS 1 (1969 – 1974)NWTS 1 (1969 – 1974) D’Angio GJ, et al. Cancer 64:349-360, 1989D’Angio GJ, et al. Cancer 64:349-360, 1989

• Is postoperative radiotherapy necessary Is postoperative radiotherapy necessary in group I disease?in group I disease?

• Is single agent chemo with vincristine or Is single agent chemo with vincristine or actinomycin D equivalent to combining actinomycin D equivalent to combining these drugs for group II and III disease?these drugs for group II and III disease?

• Is preoperative vincristine of value in Is preoperative vincristine of value in group IV disease?group IV disease?

• Radiation doses adjusted for ageRadiation doses adjusted for age Birth – 18 mo 18 to 24 GyBirth – 18 mo 18 to 24 Gy 18 – 30 mo 24 to 30 Gy18 – 30 mo 24 to 30 Gy 31- 40 mo 30 to 35 Gy31- 40 mo 30 to 35 Gy 41 mo or older 35 – 40 Gy41 mo or older 35 – 40 Gy

NWTS 1 ResultsNWTS 1 Results

Post-op XRT not needed for group I <2 Post-op XRT not needed for group I <2 yoyo

Actino/Vincr better than either agent Actino/Vincr better than either agent alone for group II and IIIalone for group II and III

Preop vincristine not useful in group IVPreop vincristine not useful in group IV RFS for group I patients >2 yo w/Actino RFS for group I patients >2 yo w/Actino

+RT 84%+RT 84% RFS for group II/III w/Actino/Vincr/XRT RFS for group II/III w/Actino/Vincr/XRT

84%84%

NWTS 1 ResultsNWTS 1 Results 2-year relapse free survival2-year relapse free survival

Favorable histology 89%Favorable histology 89% Unfavorable histology 29%Unfavorable histology 29%

Poor prognostic factorsPoor prognostic factors Large tumor sizeLarge tumor size Lymph node involvementLymph node involvement Age >2 yearsAge >2 years

No radiation dose response between 10-40 GyNo radiation dose response between 10-40 Gy Delays of up to 10 days for post-op tx found Delays of up to 10 days for post-op tx found

acceptableacceptable Whole abdominal XRT not necessary for Whole abdominal XRT not necessary for

tumor spills confined to the flanktumor spills confined to the flank

NWTS 2 1974- 1979NWTS 2 1974- 1979

Can Vincr & Actino substitute for Can Vincr & Actino substitute for RT in older children with Group I RT in older children with Group I disease?disease?

Are protracted periods of adjuvant Are protracted periods of adjuvant Vincr & Actino helpful for Groups II Vincr & Actino helpful for Groups II – IV?– IV?

Is addition of Adriamycin to Actino Is addition of Adriamycin to Actino and Vincr of value in Groups II – IV?and Vincr of value in Groups II – IV?


Vincr & Actino can substitute for RT Vincr & Actino can substitute for RT in Group I diseasein Group I disease

6 months = 15 months Actino/Vincr 6 months = 15 months Actino/Vincr for Group Ifor Group I

Addition of Adria to Actino/Vincr/XRT Addition of Adria to Actino/Vincr/XRT for Groups II-IV provided benefitfor Groups II-IV provided benefit

Worse 2-year survival for lymph node Worse 2-year survival for lymph node + (54% vs 82%) and patients with + (54% vs 82%) and patients with unfavorable histology (54% vs 90%)unfavorable histology (54% vs 90%)

NWTS 3 1979 – 1985NWTS 3 1979 – 1985 Green DM, et al. Pediatr Clin North Am Green DM, et al. Pediatr Clin North Am

38:475-488, 199138:475-488, 1991 Patients stratified by Stage instead of GroupPatients stratified by Stage instead of Group FH & UH incorporated in the treatment algorithmFH & UH incorporated in the treatment algorithm Five questionsFive questions

Can duration of chemotherapy shortened for Stage I Can duration of chemotherapy shortened for Stage I FH? FH?

Can RT be eliminated for Stage II FH?Can RT be eliminated for Stage II FH? What is the minimum effective RT dose for Stage III What is the minimum effective RT dose for Stage III

FH?FH? Is Adriamycin clearly beneficial and necessary for Is Adriamycin clearly beneficial and necessary for

Stages II & III FH?Stages II & III FH? Will Cyclophosphamide improve survival in Stages I – IV Will Cyclophosphamide improve survival in Stages I – IV

UH and Stage IV FH?UH and Stage IV FH?

NWTS 3NWTS 3

• Stage I FH: Vinc/Actino (no RT) 24 vs Stage I FH: Vinc/Actino (no RT) 24 vs 10 weeks10 weeks

• Stage II FH: 3 vs. 2 drugs (? Adriamycin Stage II FH: 3 vs. 2 drugs (? Adriamycin necessity), +/- XRT 20 Gynecessity), +/- XRT 20 Gy

• Stage III FH: 10 vs. 20 Gy, 3 vs. 2 drugsStage III FH: 10 vs. 20 Gy, 3 vs. 2 drugs• Stage IV FH and all UH: XRT/3 drugs Stage IV FH and all UH: XRT/3 drugs

+/- cyclophosphamide+/- cyclophosphamide


Stage I: 10 wks vs. 6 months equivalent Stage I: 10 wks vs. 6 months equivalent (VA)(VA) 4-year RFS 89% OS 96%4-year RFS 89% OS 96%

Stage II: no difference between 2 or 3 Stage II: no difference between 2 or 3 drugs with or without XRTdrugs with or without XRT 4-year RFS 87% OS 91%4-year RFS 87% OS 91%

Stage III: No stat sig difference in Stage III: No stat sig difference in abdominal relapse between 10 and 20 Gy, abdominal relapse between 10 and 20 Gy, trend favored use of Adriamycin or 20 Gytrend favored use of Adriamycin or 20 Gy 4-year RFS 82% OS 91%4-year RFS 82% OS 91%


Stage IV: 4 drugs equal to 3 drugs Stage IV: 4 drugs equal to 3 drugs (both include abdominal and lung XRT)(both include abdominal and lung XRT) 4-year RFS 79% OS 80%4-year RFS 79% OS 80%

AnaplasiaAnaplasia 4 drugs better than 3 drugs for stage II-IV4 drugs better than 3 drugs for stage II-IV Clear cell sarcoma patients had trend Clear cell sarcoma patients had trend

toward improvement with toward improvement with CyclophosphamideCyclophosphamide

25% OS for rhabdoid in both arms25% OS for rhabdoid in both arms

NWTS 4 1986 - 1994NWTS 4 1986 - 1994

Addressed issues of minimization of Addressed issues of minimization of therapy and customization by Stage therapy and customization by Stage & Histology& Histology

Evaluate the role of pulse dosed Evaluate the role of pulse dosed chemotherapychemotherapy

NWTS 4 SchemaNWTS 4 Schema


Pulse–intensive chemotherapy Pulse–intensive chemotherapy feasible, produce less hematologic feasible, produce less hematologic toxicity and allow for increased drug toxicity and allow for increased drug dose-intensitydose-intensity

Cost analysis showed savings of Cost analysis showed savings of $790,000 a year in the US if all $790,000 a year in the US if all Wilms’ patients were treated on Wilms’ patients were treated on pulse-intensive regimenspulse-intensive regimens

NWTS 5 SchemaNWTS 5 Schema

NWTS 5 ResultsNWTS 5 ResultsLOH 1p / 16qLOH 1p / 16q

LOH 1p associated with significantly worse LOH 1p associated with significantly worse RFS in Stage II but not Stage III/IVRFS in Stage II but not Stage III/IV

Suggests that adverse effects of LOH 1p Suggests that adverse effects of LOH 1p can be overcome by more aggressive can be overcome by more aggressive chemotherapychemotherapy

NWTS 5 Selected Results NWTS 5 Selected Results - FH- FH

Stage I FH 4 y RFS 92% OS 98%Stage I FH 4 y RFS 92% OS 98% Stage II FH 4 y RFS 83% OS 92%Stage II FH 4 y RFS 83% OS 92% Stage III FH (included RT) 4 y RFS Stage III FH (included RT) 4 y RFS

85.3% OS 93.9%85.3% OS 93.9% Stage IV FH 4 y EFS 74.6% (most of Stage IV FH 4 y EFS 74.6% (most of

these patients had lung mets and these patients had lung mets and received pulmonary RT)received pulmonary RT)

NWTS 5 Selected Results NWTS 5 Selected Results UHUH

Diffuse Anaplasia Diffuse Anaplasia 2 y EFS2 y EFS Stage I 64.3 %Stage I 64.3 % Stage II 79.5%Stage II 79.5% Stage III 62.7%Stage III 62.7% Stage IV 33.6%Stage IV 33.6%

CCSKCCSK Stage I –IV 4y RFS Stage I –IV 4y RFS

77.6%77.6% 6/9 Stage IV 6/9 Stage IV

patients relapsedpatients relapsed

Rhabdoid Tumors Rhabdoid Tumors Stage I 50%Stage I 50% Stage II 33.3%Stage II 33.3% Stage III 33.3%Stage III 33.3% Stage IV 21.4 %Stage IV 21.4 % Stage V 0%Stage V 0%

Selected Results from Selected Results from NWTS 5NWTS 5

High rate relapse for Stage I patients with High rate relapse for Stage I patients with diffuse anaplasia (10/29 patients, 5 deaths); diffuse anaplasia (10/29 patients, 5 deaths); 4 y/o RFS 64.3 %4 y/o RFS 64.3 %

High rate of relapse for Stage I focal High rate of relapse for Stage I focal anaplasia (3/9 patients, 2 deaths)anaplasia (3/9 patients, 2 deaths)

Improved control of Stage I CCSK patients 4 Improved control of Stage I CCSK patients 4 y/o RFS 100% (0/14 patients)y/o RFS 100% (0/14 patients)

There was a subset of “very low risk” There was a subset of “very low risk” patients - < 2 years, Stage I FH, <550 g who patients - < 2 years, Stage I FH, <550 g who were initially assigned to NO adjuvant were initially assigned to NO adjuvant therapy; interim analysis showed 2 y EFS therapy; interim analysis showed 2 y EFS 86.5% which was lower than expected; this 86.5% which was lower than expected; this arm was subsequently closedarm was subsequently closed

Current ProtocolsCurrent Protocols

AREN 0532AREN 0532 FH Stage I through FH Stage III FH Stage I through FH Stage III

Standard RiskStandard Risk

AREN 0533 / AREN 0321AREN 0533 / AREN 0321

AREN 0533 AREN 0533 FH Stage III High RiskFH Stage III High Risk FH Stage IVFH Stage IV

AREN 0321AREN 0321 UH Wilms’UH Wilms’ Clear Cell Sarcoma of the KidneyClear Cell Sarcoma of the Kidney Rhabdoid TumorRhabdoid Tumor RCCRCC

AREN 0533AREN 0533

Eliminate pulmonary

RT in Stage IV FH Rapid Responders

Who gets XRT todayWho gets XRT today Favorable HistologyFavorable Histology

Stage I & II NO RTStage I & II NO RT Stage IIIStage III RT to Tumor RT to Tumor

Bed (10.8 Gy) or Whole Bed (10.8 Gy) or Whole Abdomen RT (10.5 Gy**)Abdomen RT (10.5 Gy**)

Stage IVStage IV RT to tumor bed RT to tumor bed or Whole abdomen if the or Whole abdomen if the primary tumor would primary tumor would have otherwise qualified have otherwise qualified as Stage III; RT to as Stage III; RT to metastasesmetastases

Stage VStage V – Stage each side – Stage each side independently; if Stage III independently; if Stage III then treat as abovethen treat as above

Anaplastic HistologyAnaplastic Histology Stage IStage I Localized RT Localized RT

to tumor bed (10.8 Gy)to tumor bed (10.8 Gy) Stage IIStage II – Localized RT – Localized RT

to tumor bed (10.8 Gy)to tumor bed (10.8 Gy) Stage IIIStage III – Localized – Localized

RT to tumor bed (19.8 RT to tumor bed (19.8 Gy) or Whole Abdomen Gy) or Whole Abdomen (19.5 - 21 Gy)(19.5 - 21 Gy)

Stage IV – If primary – If primary tumor would qualify as tumor would qualify as Stage I then no RT; if Stage I then no RT; if Stage II or III as above; Stage II or III as above; RT to metastasesRT to metastases

Who gets XRT todayWho gets XRT today

Clear Cell Sarcoma of the Kidney Clear Cell Sarcoma of the Kidney Stage I – NO RT except for if LN Stage I – NO RT except for if LN

sampling or pathology review not sampling or pathology review not performed (0 -10.8 Gy)performed (0 -10.8 Gy)

Stage II – Localized RT to tumor bed (10.8 Stage II – Localized RT to tumor bed (10.8 Gy)Gy)

Stage III – Localized or Whole Abdomen** Stage III – Localized or Whole Abdomen** akin to FH Stage III (10.8 Gy/10.5 Gy**)akin to FH Stage III (10.8 Gy/10.5 Gy**)

Stage IV – Treat primary tumor again Stage IV – Treat primary tumor again based on Stage; treat metastasesbased on Stage; treat metastases

Who gets XRT today?Who gets XRT today?

Rhabdoid Tumor Rhabdoid Tumor Stage I – Localized RT to tumor bedStage I – Localized RT to tumor bed Stage II – Localized RT to tumor bedStage II – Localized RT to tumor bed Stage III – Localized or Whole Stage III – Localized or Whole

Abdomen** akin to FH Stage IIIAbdomen** akin to FH Stage III Stage IV – Treat primary tumor again Stage IV – Treat primary tumor again

based on Stage; treat metastasesbased on Stage; treat metastases All stages get RT!!! Dose is age-All stages get RT!!! Dose is age-

dependentdependent <12 months 10.8 Gy<12 months 10.8 Gy ≥ ≥ 12 months 19.8 Gy /19.5 - 21 Gy**12 months 19.8 Gy /19.5 - 21 Gy**

M.K.M.K.

20 mo girl with Rhabdoid Tumor of 20 mo girl with Rhabdoid Tumor of the kidney with presumed metastases the kidney with presumed metastases to bone and lungs; intraop tumor to bone and lungs; intraop tumor spillagespillage

Dx: 4/3/07Dx: 4/3/07 Treated per protocol AREN0321Treated per protocol AREN0321 Recommendations would be for RTRecommendations would be for RT

Whole lung to 12 GyWhole lung to 12 Gy Femur met to 25.2 GyFemur met to 25.2 Gy Whole abdomen to 19.5-21 GyWhole abdomen to 19.5-21 Gy

Current Radiotherapy Current Radiotherapy GuidelinesGuidelines

Tumor Bed/Flank RTTumor Bed/Flank RT XRT should start by day 10 post-op (surgery XRT should start by day 10 post-op (surgery

day is day 1) but no later than day 14day is day 1) but no later than day 14 Fraction size is 1.8 Gy unless large fieldFraction size is 1.8 Gy unless large field Radiation dose for flank/tumor bed is 10.8 Gy Radiation dose for flank/tumor bed is 10.8 Gy

exceptexcept Stage III Diffuse Anaplasia & Rhabdoid Tumor 19.8 Stage III Diffuse Anaplasia & Rhabdoid Tumor 19.8

GyGy Boost gross residual disease with additional 9 -Boost gross residual disease with additional 9 -

10.8 Gy10.8 Gy Limit dose to more than ½ of uninvolved liver Limit dose to more than ½ of uninvolved liver

to 19.8 Gyto 19.8 Gy

Current Radiotherapy Current Radiotherapy GuidelinesGuidelines

Tumor Bed/Flank RTTumor Bed/Flank RT Dose to more than 1/3 of the contralateral Dose to more than 1/3 of the contralateral

kidney or residual kidney for bilateral kidney or residual kidney for bilateral Wilms’ should not exceed 14.4 GyWilms’ should not exceed 14.4 Gy

Tumor Bed is determined by pre-operative Tumor Bed is determined by pre-operative CTCT

Includes kidney + tumor + 1 cm marginIncludes kidney + tumor + 1 cm margin Treat all of the vertebral body to avoid Treat all of the vertebral body to avoid

scoliosisscoliosis Recommend AP/PA for fields; IMRT allowed Recommend AP/PA for fields; IMRT allowed

for boostfor boost

Treatment Fields - FlankTreatment Fields - Flank

Treatment Fields – Whole Treatment Fields – Whole AbdomenAbdomen

Used for patients with diffuse peritoneal seeding, Used for patients with diffuse peritoneal seeding, gross tumor spillage within the abdominal cavity gross tumor spillage within the abdominal cavity during surgery or pre-op intraperitoneal ruptureduring surgery or pre-op intraperitoneal rupture

Portals Portals Superior – 1 cm above diaphragm Superior – 1 cm above diaphragm Inferior – Bottom of obturator foramenInferior – Bottom of obturator foramen Lateral – 1 cm beyond lateral abdominal wallLateral – 1 cm beyond lateral abdominal wall Shield femoral headsShield femoral heads

Total Dose 10.5 Gy (1.5 Gy / fx) except for patients Total Dose 10.5 Gy (1.5 Gy / fx) except for patients with Diffuse Anaplasia or Rhabdoid Tumors (19.5 – with Diffuse Anaplasia or Rhabdoid Tumors (19.5 – 21 Gy)21 Gy)

If need to boost for diffuse unresectable peritoneal If need to boost for diffuse unresectable peritoneal implants then can treat whole abdomen to 21 Gy; implants then can treat whole abdomen to 21 Gy; shield remaining kidney to not get more than 14.4 shield remaining kidney to not get more than 14.4 GyGy

Treatment Fields – Whole Treatment Fields – Whole AbdomenAbdomen

A.M.A.M.

3 yo 10 month girl3 yo 10 month girl Presented with one day of severe abd painPresented with one day of severe abd pain Outside ED: UA + blood, Tx to OHSU EDOutside ED: UA + blood, Tx to OHSU ED U/S 12 x 12 cm abd massU/S 12 x 12 cm abd mass CT c/a/p: 12 x 12 x 13.6 cm RUQ mass CT c/a/p: 12 x 12 x 13.6 cm RUQ mass

arising from upper pole of kidney with arising from upper pole of kidney with evidence of tumor rupture; no evidence of evidence of tumor rupture; no evidence of metsmets

Admitted to DCHAdmitted to DCH

A.M.A.M.

A.M.A.M.

4/6/07: Taken to OR for attempted 4/6/07: Taken to OR for attempted resection but biopsy only secondary to resection but biopsy only secondary to size of tumor; then developed size of tumor; then developed compartment syndromecompartment syndrome

Path: favorable histology Wilm’sPath: favorable histology Wilm’s 4/9/07: Resection with spillage of tumor 4/9/07: Resection with spillage of tumor

into abdomen; + bx’s of diaphragm, liver, into abdomen; + bx’s of diaphragm, liver, adrenal and rectocaval fibrous tissueadrenal and rectocaval fibrous tissue

STAGE III Favorable Histology Wilm’sSTAGE III Favorable Histology Wilm’s

A.M. TreatmentA.M. Treatment

Resection: 4/9/07Resection: 4/9/07 Tumor spillageTumor spillage

ChemotherapyChemotherapy DD4ADD4A

RT: 4/18/07RT: 4/18/07 Whole AbdomenWhole Abdomen AP:PAAP:PA Dose: 1050 cGy (150 cGy x 7)Dose: 1050 cGy (150 cGy x 7)

A.M. DRRA.M. DRR

A.M. DVHA.M. DVH

Current Radiotherapy Current Radiotherapy Guidelines – Lung Guidelines – Lung

IrradiationIrradiation AREN 0533 allows for omission of Lung RT AREN 0533 allows for omission of Lung RT

in FH patients who achieve CR with 3 drug in FH patients who achieve CR with 3 drug chemotherapy (based on CT scan at Week 6)chemotherapy (based on CT scan at Week 6)

Whole Lung XRT for patients with CXR & CT Whole Lung XRT for patients with CXR & CT defined pulmonary metastases is 12 Gy / 8 fx (1.5 defined pulmonary metastases is 12 Gy / 8 fx (1.5 Gy /fx); 10.5 Gy if < 12 months oldGy /fx); 10.5 Gy if < 12 months old

Localized foci of lung disease persisting 2 weeks Localized foci of lung disease persisting 2 weeks after 12 Gy can be excised or given additional 7.5 after 12 Gy can be excised or given additional 7.5 GyGy

Treat both lungs regardless of the number or Treat both lungs regardless of the number or location of visible metastaseslocation of visible metastases

Patients with CT only pulmonary mets – at the Patients with CT only pulmonary mets – at the discretion of the treating institutiondiscretion of the treating institution

Current Radiotherapy Current Radiotherapy Guidelines – Lung Guidelines – Lung

IrradiationIrradiation Treatment FieldsTreatment Fields

Superior border – Above the ClaviclesSuperior border – Above the Clavicles Inferior border - Approximately to L1Inferior border - Approximately to L1

Caution with lung boosts; upto 10% rate of Caution with lung boosts; upto 10% rate of pneumonopathy in patients who received 14 pneumonopathy in patients who received 14 Gy whole lung RT or large volume RTGy whole lung RT or large volume RT

In infants < 18 months, trial of In infants < 18 months, trial of chemotherapy alone is suggested; if chemotherapy alone is suggested; if resolution of lung mets does not occur within resolution of lung mets does not occur within 4 weeks of therapy; then give 9 Gy to both 4 weeks of therapy; then give 9 Gy to both lungs with a single 1.5 Gy boost to specific lungs with a single 1.5 Gy boost to specific nodulesnodules

Treatment Fields - LungsTreatment Fields - Lungs

Pulmonary RTPulmonary RT Rationale behind omitting upfront Rationale behind omitting upfront

pulmonary RT comes from several studiespulmonary RT comes from several studies SIOP 9 SIOP 9

Stage IV patients with pre-op chemotherapyStage IV patients with pre-op chemotherapy 57/59 patients had lung metastases; 56 had FH57/59 patients had lung metastases; 56 had FH 40/59 patients had CR in the lung to 40/59 patients had CR in the lung to

chemotherapy or additional metastatectomychemotherapy or additional metastatectomy In these 40 patients, 4 y RFS was 67.5% and OS In these 40 patients, 4 y RFS was 67.5% and OS

was 87.5% 70% of these patients were spared was 87.5% 70% of these patients were spared whole – lung irradiationwhole – lung irradiation

When sub group analysis done by histology; in When sub group analysis done by histology; in FH OS was 82.9%FH OS was 82.9%

CT only Pulmonary CT only Pulmonary Metastases – NWTS 4 & 5Metastases – NWTS 4 & 5

In NWTS 4& 5 pulmonary mets were In NWTS 4& 5 pulmonary mets were defined as presence of nodules on CXRdefined as presence of nodules on CXR

There were 171 patients with CT only There were 171 patients with CT only detected mets but not CXRdetected mets but not CXR

29 were Stage I or II and received 29 were Stage I or II and received Vincr + Actino D Vincr + Actino D 5 y EFS 54% 5 y EFS 54%

58 were Stage III and received Vincr + 58 were Stage III and received Vincr + Actino D + Adriamycin Actino D + Adriamycin 5 y EFS 81% 5 y EFS 81%

84 were Stage IV and majority received 84 were Stage IV and majority received pulmonary XRT pulmonary XRT 5 y EFS 78% 5 y EFS 78%

CT only Pulmonary CT only Pulmonary MetastasesMetastases

Patients who received Lung XRT had Patients who received Lung XRT had 1 pulmonary relapse, 1 pulmonary 1 pulmonary relapse, 1 pulmonary progression and 5 toxic deaths (2 progression and 5 toxic deaths (2 attributed to pulmonary RT)attributed to pulmonary RT)

Patients who did not receive Lung Patients who did not receive Lung XRT had 6 pulmonary relapses; no XRT had 6 pulmonary relapses; no toxic deathstoxic deaths

C.H.C.H.

3 yo girl3 yo girl Presented with one week of fussiness, Presented with one week of fussiness,

abdominal painabdominal pain Mom palpated mass in abdomenMom palpated mass in abdomen Saw PCP-direct admit to DCHSaw PCP-direct admit to DCH U/S abd and CT abd showed Rt renal U/S abd and CT abd showed Rt renal

mass with IVC involvementmass with IVC involvement CXR/CT chest: multiple pulmonary CXR/CT chest: multiple pulmonary

nodulesnodules

C.H.C.H.

C.H.C.H. Surgery on 4/20/07: Complete resection/ Surgery on 4/20/07: Complete resection/

Rt nephrectomy with minimal tumor Rt nephrectomy with minimal tumor spillage confined to the renal hilumspillage confined to the renal hilum

Dx: Stage IV favorable histology Wilm’sDx: Stage IV favorable histology Wilm’s Chemo: per NWTS-5, regimen DD4AChemo: per NWTS-5, regimen DD4A RT:RT:

Whole lung/Rt flank began on 4/30/07Whole lung/Rt flank began on 4/30/07 AP:PAAP:PA 1200 cGy (150 cGy x 8 fx)1200 cGy (150 cGy x 8 fx) Will get CT chest 2 weeks out (5/24) and if Will get CT chest 2 weeks out (5/24) and if

persistent bulky disease may boost with 750 persistent bulky disease may boost with 750 cGycGy

Hicks DRRHicks DRR

Hicks DVHHicks DVH

Current Radiotherapy Current Radiotherapy Guidelines - MetastasesGuidelines - Metastases

LiverLiver Use RT only if lesions unresectable Use RT only if lesions unresectable

because of location or extentbecause of location or extent Tumor + 2 cm margin; 1.8 Gy / fractionTumor + 2 cm margin; 1.8 Gy / fraction Treat to 25.2 Gy to 39.6 GyTreat to 25.2 Gy to 39.6 Gy Limit dose to 75 % of liver to less than Limit dose to 75 % of liver to less than

30.6 Gy30.6 Gy If whole liver involved, treat to 19.8 GyIf whole liver involved, treat to 19.8 Gy Limit dose to remaining kidney to 14.4 Gy Limit dose to remaining kidney to 14.4 Gy

with a posterior blockwith a posterior block

Current Radiotherapy Current Radiotherapy Guidelines - MetastasesGuidelines - Metastases

BrainBrain Whole Brain XRT to 21.6 Gy then boost of Whole Brain XRT to 21.6 Gy then boost of

10.8 Gy (1.8 Gy/fx)10.8 Gy (1.8 Gy/fx) Bone Bone

25.2 Gy25.2 Gy Entire bone does not need to be treatedEntire bone does not need to be treated 3 cm margin3 cm margin

Lymph Node (Not Surgically removed)Lymph Node (Not Surgically removed) 19.8 Gy19.8 Gy

Adolescent and young adults (≥ 16 years) Adolescent and young adults (≥ 16 years) receive 30.6 Gy to sites of metastasesreceive 30.6 Gy to sites of metastases

Treatment of RelapseTreatment of Relapse

Children with relapsed FH Wilm’s Children with relapsed FH Wilm’s can have a favorable outcome based can have a favorable outcome based on on Initial StageInitial Stage Time from initial diagnosisTime from initial diagnosis Site of relapseSite of relapse Previous therapyPrevious therapy

Treatment of RelapseTreatment of Relapse

Adverse factors for relapsed Wilms’Adverse factors for relapsed Wilms’ Prior Adriamycin based chemotherapyPrior Adriamycin based chemotherapy Relapse < 12 months from initial Relapse < 12 months from initial

diagnosisdiagnosis Intra-abdominal relapse after previous Intra-abdominal relapse after previous

abdominal RTabdominal RT

Treatment of RelapseTreatment of RelapseRestagingRestaging

Stage 1R – Localized Disease, completely Stage 1R – Localized Disease, completely excisedexcised

Stage 2R – Gross total resection with Stage 2R – Gross total resection with evidence of regional spreadevidence of regional spread

Stage 3R – Residual non-hematogenous Stage 3R – Residual non-hematogenous tumor present and confined to abdomentumor present and confined to abdomen

Stage 4R – Hematogenous mets presentStage 4R – Hematogenous mets present Stage 5R – bilateral Renal involvementStage 5R – bilateral Renal involvement

Treatment of Relapse – Treatment of Relapse – Radiotherapy GuidelinesRadiotherapy Guidelines

Radiotherapy is administered to Radiotherapy is administered to patients at site of relapsepatients at site of relapse

Dose to infradiaphragmatic sitesDose to infradiaphragmatic sites Complete Remission after Surgery Complete Remission after Surgery

(1R/2R) who have either received no (1R/2R) who have either received no previous RT or have received 10.8 Gyprevious RT or have received 10.8 Gy Birth – 12 months – 12.6 - 18 GyBirth – 12 months – 12.6 - 18 Gy 13 months or older – 21.6 Gy13 months or older – 21.6 Gy

Gross Residual Disease after SurgeryGross Residual Disease after Surgery Should get a boostShould get a boost Total dose including boost should not exceed Total dose including boost should not exceed

30 Gy30 Gy


Dose to infradiaphragmatic sitesDose to infradiaphragmatic sites Total Nominal Dose (including previous RT)Total Nominal Dose (including previous RT)

<36 months – should not exceed 30.6 Gy<36 months – should not exceed 30.6 Gy >36 months – should not exceed 39.6 Gy>36 months – should not exceed 39.6 Gy

Total Spine dose should not exceed 41.4 GyTotal Spine dose should not exceed 41.4 Gy Total Liver dose should not exceed 30.6 GyTotal Liver dose should not exceed 30.6 Gy Total Remaining Kidney dose should not Total Remaining Kidney dose should not

exceed 19.8 Gyexceed 19.8 Gy


Lung IrradiationLung Irradiation Complete remission & No previous RTComplete remission & No previous RT

≤ ≤ 18 months: 9 Gy; 1.5 Gy/fx18 months: 9 Gy; 1.5 Gy/fx > 18 months: 12 Gy, 1.5 Gy/fx> 18 months: 12 Gy, 1.5 Gy/fx

Gross Residual Disease after surgical Gross Residual Disease after surgical resection & No previous RTresection & No previous RT Can boost gross disease with additional 7.5 Can boost gross disease with additional 7.5

GyGy

Liver, Brain, Bone metsLiver, Brain, Bone mets Follow guidelines from NWTS 5Follow guidelines from NWTS 5

L.L.L.L.

4/06 Dx with Stage I favorable 4/06 Dx with Stage I favorable histology Wilm’s at age 3histology Wilm’s at age 3

S/p complete resection Rt renal S/p complete resection Rt renal mass/nephrectomymass/nephrectomy

Chemo: Chemo: CCG 5941 protocol/regimen EE4ACCG 5941 protocol/regimen EE4A 18 weeks Vincr/Actino18 weeks Vincr/Actino Finished chemo 7/06Finished chemo 7/06

Close f/uClose f/u

L.L.L.L.

Regular F/U appt 3/14/07Regular F/U appt 3/14/07 AsymptomaticAsymptomatic Abd U/S: 5.6 cm mass in Rt renal Abd U/S: 5.6 cm mass in Rt renal

fossafossa CT abdomen: 5.9 x 4.3 cm CT abdomen: 5.9 x 4.3 cm

homogeneous mass in Rt renal fossahomogeneous mass in Rt renal fossa CT chest: no metastatic diseaseCT chest: no metastatic disease

LawsonLawson

L.L.L.L. Surgery on 3/19/07: complete resectionSurgery on 3/19/07: complete resection Pathology: Recurrent favorable histology Pathology: Recurrent favorable histology

Wilm’sWilm’s Stage 1RStage 1R Chemotherapy: Vincristine, Actinomycin Chemotherapy: Vincristine, Actinomycin

D per NWTS-5 relapse protocol, regimen D per NWTS-5 relapse protocol, regimen 11

RT began 4/13/07RT began 4/13/07 2160 cGy to Rt flank2160 cGy to Rt flank 180 cGy x 12 fx180 cGy x 12 fx AP:PAAP:PA

L.L. DRRL.L. DRR

L.L. DVHL.L. DVH

T.B.T.B. 12 yo girl with hx of Stage IV Wilm’s Tumor 12 yo girl with hx of Stage IV Wilm’s Tumor

dx in December 2003dx in December 2003 Tx’ed with chemo (Vincr/Actino/Doxo) and Tx’ed with chemo (Vincr/Actino/Doxo) and

RT (12 Gy to whole lung/whole abd)RT (12 Gy to whole lung/whole abd) 8/2004: relapse with pulmonary nodules tx 8/2004: relapse with pulmonary nodules tx

with carbo/etop/ifos/melphalan w/ stem cell with carbo/etop/ifos/melphalan w/ stem cell rescuerescue

2/06: abdominal relapse s/p resection and 2/06: abdominal relapse s/p resection and carbo/topotecancarbo/topotecan

2/07: 4 x 10 cm mass in left ileopsoas muscle 2/07: 4 x 10 cm mass in left ileopsoas muscle with extension into spinal canal at T12-L1with extension into spinal canal at T12-L1

T.B.T.B.

Tx: Palliative RTTx: Palliative RT RT to left flankRT to left flank 2520 cGy2520 cGy 180 cGy x 14 fx180 cGy x 14 fx Total abd dose = 3720 cGy Total abd dose = 3720 cGy

(including RT in 2003) (including RT in 2003)

Beach DRRBeach DRR

AcknowledgementsAcknowledgements

Dr. Carol Marquez (for teaching us Dr. Carol Marquez (for teaching us everything I know about Wilms’)everything I know about Wilms’)

Dr. Charles Thomas Dr. Charles Thomas Dr. Kamal PatelDr. Kamal Patel Dr. Christopher LeeDr. Christopher Lee

wilms’ tumor – indications for radiotherapy tasha mcdonald m.d. parag sanghvi m.d. department of...

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