Cattolica, 1/3/07

CSSTUMORE DI WILMS

F. Fossati Bellani

Cattolica, 1/3/07

attività svolte/in corso

Cattolica, 1/3/07

Protocollo TW AIEOP 2003217 casi Tumori Primitivi Rene

204 casi registrati46/204

NON eleggibili:

TW bilaterale, 11nefroma M, 11nefroma C, 4

RCC, 9altro istotipo, 5

pre-trattamento CT, 1età > 18 anni, 5

9/158NON inclusi:

Terapia ≠ Protocollo:Down S, 1WAGR, 1

altro, 2TRR, 2

prima CE INT, 3

149 inclusinello studio

revisioneistologica:100 (67%)

tessuto perstudi biologici:

111 (75%)

diagnosi eleggibiliTW, 146SCCR, 7TRR, 5

Cattolica, 1/3/07

istologia(P Collini)

• 73% revisione diagnosi istologica (151/204)– 67% dei casi eleggibili (CNR-92: 32-40%)

– rivisti 30 vetrini/caso (media), range 3-120– % discordanza su istotipo o anaplasia < 5%– % discordanza su stadio 5%

Cattolica, 1/3/07

TW 2003: sopravvivenza

91.7 (8)59.2 (15)59.2 (15)IV

97 (1.8)94.4 (3) (3-yr)

86 (3.3)83.2 (4.3) (3-yr)

86.7 (3.3)83.8 (4.2) (3-yr)

tutti gli stadi

10087.3 (6.9)87.3 (6.9)III

95 (3.6)89.6 (4.4)91.4 (4.1)II

10090.6 (5.2)90.6 (5.2)I

2-yr OS2-yr EFS2-yr % DFS (SE)TW

fullow-up mediano 24 mesi (range: 2-44)mediana recidiva: 7 mesi (range: 2-31)104/135 casi con f-up ≥ 12 mesi dalla diagnosi

Cattolica, 1/3/07

TW, tutti gli stadi

0

,2

,4

,6

,8

1

Cum

. Sur

viva

l

0 6 12 18 24 30 36 42months

Kaplan-MeierCensor Variable: STATUS 3-year DFS

0

,2

,4

,6

,8

1

Cum

. Sur

viva

l

0 6 12 18 24 30 36 42

months

Kaplan-MeierCensor Variable: STATUS 3-year OS

83.8 ±4.216/135

94.4 ±34/135

Cattolica, 1/3/07

DFS - stadio

0

,2

,4

,6

,8

1

Cum

. Sur

viva

l

0 6 12 18 24 30 36 42

months

Kaplan-MeierCensor Variable: STATUS 2- year DFS

(5 eventi/19)59.2 ±15IV(3 eventi/29)87.3 ±6.9III(3 eventi/36)90.6 ±5.2I(5 eventi/51)91.4 ±4.1II

Cattolica, 1/3/07

DOXO 350 mg/m2

1 anno

Idem come sopra

18 X VCRACTD

∼ 6 mesi

CNR 80

1980-87

DOXO 240 mg/m2

RT da sett. 2(34 sett.)

DOXO 360 mg/m2

RT da sett. 10(40 sett.)

III4 X VCR

2 X DACT8 x VCR

4 X DACT2 X DOXO

CT pre-op

12 X CVR9 X DACT22 sett.

14 X VCR9 X DACT

25 sett.II

6 X VCR3 X DACT

6 sett.

8 X VCR3 X DACT

8 sett.I

AIEOP 2003CNR/AIEOP 92stadio

2003-1992-2000

carico terapeutico

Cattolica, 1/3/07

0

,2

,4

,6

,8

1

Cum

. Sur

viva

l

0 6 12 18 24 30 36 42months

Kaplan-MeierCensor Variable: STATUS 2-year EFS

59.2% (15)IV87.3% (6.9)III89.6% (4.4)II90.6% (5.2)I

Cattolica, 1/3/07

pattern recidiva(TW stadio I, II, III)

5/11 (45%)

13/35 (37%)

solo polmone

3/11 (27%)

20/35 (57%)

intra-addome

TW 2003CNR-92

Cattolica, 1/3/07

rotture tumorali

2.6%

CNR-92

spillagechirurgico

qualsiasi spillage

10,6%10-12%

19%13-16%

NWTS-5J Ped Surg 40:208,2005

TW 2003

Cattolica, 1/3/07

pattern recidiva(TW stadio I, II, III)

5/11 (45%)

13/35 (37%)

solo polmone

3/11 (27%)

20/35 (57%)

intra-addome

TW 2003CNR-92

3/11 rene controlaterale

Cattolica, 1/3/07

attività presente/futuro

Cattolica, 1/3/07

DFS - stadio

0

,2

,4

,6

,8

1

Cum

. Sur

viva

l

0 6 12 18 24 30 36 42

months

Kaplan-MeierCensor Variable: STATUS 2- year DFS

59.2 ±15 (5/19 casi)IV87.3 ±6.9III90.6 ±5.2I91.4 ±4.1II

fattori biologici?≠ fattori istologici?età?

Cattolica, 1/3/07

TW 2003: età

< 24 mesi 95% ±3 (2 eventi/43)> 24 mesi 78% ±4 (14 eventi/92)

Logrank p .08

0

,2

,4

,6

,8

1

Cum

. Sur

viva

l

0 6 12 18 24 30 36 42 48Time

Kaplan-Meier Cum. Survival Plot for DFSCensor Variable: STATUS 3-year DFSGrouping Variable: età < 24 mesi

Cattolica, 1/3/07

DFS - stadio

0

,2

,4

,6

,8

1

Cum

. Sur

viva

l

0 6 12 18 24 30 36 42

months

Kaplan-MeierCensor Variable: STATUS 2- year DFS

59.2 ±15 (5/19 casi)IV87.3 ±6.9III90.6 ±5.2I91.4 ±4.1II

fattori biologici?nuovi fattori istologici?età?

Cattolica, 1/3/07

DFS - stadio

0

,2

,4

,6

,8

1

Cum

. Sur

viva

l

0 6 12 18 24 30 36 42

months

Kaplan-MeierCensor Variable: STATUS 2- year DFS

59.2 ±15 (5/19 casi)IV87.3 ±6.9III90.6 ±5.2I91.4 ±4.1II

modulazione intensità terapia sulla risposta

recupero casi mancantirevisione dei casi

Cattolica, 1/3/07

pubblicazioni (2006)

• The murine Pou6f2 gene is temporally and spatially regulated during kidneyembryogenesis and its human homolog is overexpressed in a subset of Wilmstumors. Pediatr Hematol Oncol. 2006 28:791-7

• Non-chromosome 11-p syndromes in Wilms tumor patients: Clinical and cytogeneticreport of two Down syndrome cases and one Turner syndrome case. Am J MedGenet A. 2007 143:85-8

• Malignant renal tumours incidence and survival in European children (1978-1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer. 2006 42:2103-14

Cattolica, 1/3/07

azioni

• breve termine: – “rinnovare” CSS (CSS Tumori del Rene?)

• medio termine: – valutare la cooperazione extra-AIEOP per istotipi/categorie

“rare”:

• Tumore Rabdoide (Intergroup, Genova 27-28/1/07)• TW recidiva “high risk” (COG, M Malogolowkin)

– valutazione fx renale residua in pazienti lungo-sopravviventi;

Cattolica, 1/3/07

AREN0631Treatment of Children with Recurrent Favorable

Histology Wilms Tumor

Marcio H. Malogolowkin, ChairAnne Warwick, Eric Gratias, Conrad Fernandez, Kuang-Yueh Chiang, Jeff Dome, Max Coppes, Jim Anderson

Cattolica, 1/3/07

COG: AREN0631Study Design

HR Recurrent FH-WT

ICE-T

Evaluate PD

No-PD Off StudyRandomize

ICE-TStem Cell Harvest after ICE for

those randomized to HDCT+ASCT

Evaluate SD*/PD

Surgery Off Study

ICE-T HDCT+ASCTICE-T *SD w/o differentiation or necrosis

Cattolica, 1/3/07

TW recidiva “high risk”esperienza Italiana

0

,2

,4

,6

,8

1C

um. S

urvi

val

0 6 12 18 24 30 36Time

Kaplan-Meier Cum. Survival Plot for RFSCensor Variable: DFS-STATUS

66%±14%(4 events/15 pts)

median follow-up 18 months from relapse (9-35 months)

0

,2

,4

,6

,8

1

Cum

. Sur

viva

l

0 6 12 18 24 30 36Time

Kaplan-Meier Cum. Survival Plot for OSCensor Variable: OS-STATUS

49% ± 16%(5 events/15 pts)

Cattolica, 1/3/07

ifosfamideinitially given?

YES NO

CTX / ETO ICE

CTX / ETO

CBDCA/ETO

ICE

CBDCA/ETO

ICE

ICE

PBSC apheresis PBSC apheresis

MEC + PBSC rescue

surgery

radiotherapy

F SpreaficoS Dallorso

Cattolica, 1/3/07

SIOP?

Cattolica, 1/3/07

Wilms tumor genetics: a new, unX-pected twist to the story

V Huff. Cancer Cell 2007 11:105-7