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