CSS TUMORE DI WILMS F. Fossati Bellani
attività svolte/in corso
Protocollo TW AIEOP 2003 217 casi Tumori Primitivi Rene 204 casi registrati 46/204 NON eleggibili: TW bilaterale, 11 nefroma M, 11 nefroma C, 4 RCC, 9 altro istotipo, 5 pre-trattamento CT, 1 età > 18 anni, 5 9/158 NON inclusi: Terapia Protocollo: Down S, 1 WAGR, 1 altro, 2 TRR, 2 prima CE INT, 3 diagnosi eleggibili TW, 146 SCCR, 7 TRR, 5 149 inclusi nello studio revisione istologica: 100 (67%) tessuto per studi biologici: 111 (75%)
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%
TW 2003: sopravvivenza TW 2-yr % DFS (SE) 2-yr EFS 2-yr OS I 90.6 (5.2) 90.6 (5.2) 100 II 91.4 (4.1) 89.6 (4.4) 95 (3.6) III 87.3 (6.9) 87.3 (6.9) 100 IV 59.2 (15) 59.2 (15) 91.7 (8) tutti gli stadi 86.7 (3.3) 83.8 (4.2) (3-yr) 86 (3.3) 83.2 (4.3) (3-yr) 97 (1.8) 94.4 (3) (3-yr) 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
TW, tutti gli stadi Cum. Survival 1,8,6,4,2 0 Kaplan-Meier Censor Variable: STATUS 3-year DFS 0 6 12 18 24 30 36 42 months 83.8 ±4.2 16/135 Cum. Survival 1,8,6,4,2 0 Kaplan-Meier Censor Variable: STATUS 3-year OS 0 6 12 18 24 30 36 42 months 94.4 ±3 4/135
DFS - stadio Kaplan-Meier Censor Variable: STATUS 2- year DFS Cum. Survival 1,8,6,4 II I III IV 91.4 ±4.1 90.6 ±5.2 87.3 ±6.9 59.2 ±15 (5 eventi/51) (3 eventi/36) (3 eventi/29) (5 eventi/19),2 0 0 6 12 18 24 30 36 42 months
carico terapeutico 1980-87 1992-2000 2003- stadio CNR 80 CNR/AIEOP 92 AIEOP 2003 I 18 X VCR ACTD 6 mesi 8 X VCR 3 X DACT 8 sett. 6 X VCR 3 X DACT 6 sett. II Idem come sopra 14 X VCR 9 X DACT 25 sett. 12 X CVR 9 X DACT 22 sett. III DOXO 350 mg/m 2 1 anno DOXO 360 mg/m 2 RT da sett. 10 (40 sett.) DOXO 240 mg/m 2 RT da sett. 2 (34 sett.) CT pre-op 8 x VCR 4 X DACT 4 X VCR 2 X DACT 2 X DOXO
Kaplan-Meier Censor Variable: STATUS 2-year EFS Cum. Survival 1,8,6,4 I II III IV 90.6% (5.2) 89.6% (4.4) 87.3% (6.9) 59.2% (15),2 0 0 6 12 18 24 30 36 42 months
pattern recidiva (TW stadio I, II, III) CNR-92 TW 2003 intraaddome 20/35 (57%) 3/11 (27%) solo polmone 13/35 (37%) 5/11 (45%)
rotture tumorali CNR-92 TW 2003 NWTS-5 J Ped Surg 40:208,2005 qualsiasi spillage 13-16% 19% spillage chirurgico 2.6% 10-12% 10,6%
pattern recidiva (TW stadio I, II, III) CNR-92 TW 2003 intraaddome 20/35 (57%) 3/11 (27%) solo polmone 13/35 (37%) 5/11 (45%) 3/11 rene controlaterale
attività presente/futuro
DFS - stadio Kaplan-Meier Censor Variable: STATUS 2- year DFS fattori biologici? fattori istologici? età? Cum. Survival 1,8,6,4,2 II I III IV 91.4 ±4.1 90.6 ±5.2 87.3 ±6.9 59.2 ±15 (5/19 casi) 0 0 6 12 18 24 30 36 42 months
TW 2003: età Cum. Survival 1,8,6,4,2 Kaplan-Meier Cum. Survival Plot for DFS Censor Variable: STATUS 3-year DFS Grouping Variable: età < 24 mesi < 24 mesi 95% ±3 (2 eventi/43) > 24 mesi 78% ±4 (14 eventi/92) Logrank p.08 0 0 6 12 18 24 30 36 42 48 Time
DFS - stadio Kaplan-Meier Censor Variable: STATUS 2- year DFS fattori biologici? nuovi fattori istologici? età? Cum. Survival 1,8,6,4,2 II I III IV 91.4 ±4.1 90.6 ±5.2 87.3 ±6.9 59.2 ±15 (5/19 casi) 0 0 6 12 18 24 30 36 42 months
DFS - stadio Kaplan-Meier Censor Variable: STATUS 2- year DFS Cum. Survival 1,8,6,4,2 0 0 6 12 18 24 30 36 42 months II I III IV 91.4 ±4.1 90.6 ±5.2 87.3 ±6.9 59.2 ±15 (5/19 casi) modulazione intensità terapia sulla risposta recupero casi mancanti revisione dei casi
pubblicazioni (2006) The murine Pou6f2 gene is temporally and spatially regulated during kidney embryogenesis and its human homolog is overexpressed in a subset of Wilms tumors. Pediatr Hematol Oncol. 2006 28:791-7 Non-chromosome 11-p syndromes in Wilms tumor patients: Clinical and cytogenetic report of two Down syndrome cases and one Turner syndrome case. Am J Med Genet 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
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;
AREN0631 Treatment of Children with Recurrent Favorable Histology Wilms Tumor Marcio H. Malogolowkin, Chair Anne Warwick, Eric Gratias, Conrad Fernandez, Kuang-Yueh Chiang, Jeff Dome, Max Coppes, Jim Anderson
COG: AREN0631 Study Design HR Recurrent FH-WT ICE-T Evaluate No-PD Randomize PD Off Study ICE-T Stem Cell Harvest after ICE for those randomized to HDCT+ASCT Evaluate Surgery SD*/PD Off Study ICE-T ICE-T HDCT+ASCT *SD w/o differentiation or necrosis
TW recidiva high risk esperienza Italiana Kaplan-Meier Cum. Survival Plot for RFS Censor Variable: DFS-STATUS Kaplan-Meier Cum. Survival Plot for OS Censor Variable: OS-STATUS 1 1,8,8 Cum. Survival,6,4,2 66%±14% (4 events/15 pts) Cum. Survival,6,4,2 49% ± 16% (5 events/15 pts) 0 0 0 6 12 18 24 30 36 Time 0 6 12 18 24 30 36 Time median follow-up 18 months from relapse (9-35 months)
F Spreafico S Dallorso YES ifosfamide initially given? NO CTX / ETO ICE PBSC apheresis PBSC apheresis surgery CTX / ETO CBDCA/ETO CBDCA/ETO ICE ICE ICE radiotherapy MEC + PBSC rescue
SIOP?
Wilms tumor genetics: a new, unx-pected twist to the story V Huff. Cancer Cell 2007 11:105-7