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Varese, 13-‐03-‐15 Prof. A Donini
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
2
Sasako M, H Van de Velde, et al, Lancet Oncol ,2010
3
Gastric Cancer Pa9ern of Recurrence
Roviello, et al. BrJSurg, 2003 Maehara Y. et al. Br J Surg,2003
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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1995 - 2012 : 5,220 patients were diagnosed with gastric cancer in the Eindhoven Cancer Registry.
- 2,029 patients (39%) presented with metastatic disease
PC was present in 706 patients (14% of total, 35% of patients with metastatic disease)
Of these patients, 491 patients (9% of total, 24% of patients with metastatic disease) had PC as the only metastatic site
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Median survival of patients with PC as the only metastatic site was 4.6 and 3.3 months in patients with PC combined with other metastases
Resection of the primary tumor in the presence of PC resulted in a longer median survival (9.9 vs. 3.7 months)
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
Int J Cancer 2014
6
Is There a Possibility of a Cure in Patients with Gastric Peritoneal Carcinomatosis ?
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
7La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
Chemotherapy and Gastric carcinomatosis
-‐Chu (Cancer 1989) : n=100 (prospective) Palliative treatment / 5-‐FU.
0% at 10 months
-‐Sadeghi EVOCAPE 1 (Cancer 2000) : n=127. (prospective) Palliative systemic chemotherapy. Median survival : 3 months1/3 of synchronous carcinomatosis
03 La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
Patients with stage IV disease should be considered for palliative chemotherapy, which improves survival compared with best supportive care alone [28 [I, A].
“Irrespective of the positive impact of any presently available chemotherapy, the prognosis of patients with advanced gastric cancer remains desperate, with a median survival of only 7 to 10 months in most of the larger clinical studies.”
9La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
Acta Oncologica 2013
10
Median survival of patients with PC was 4 months.
In conclusion, the usage of chemotherapy increased in patients with PC of gastric origin but this did not result in prolongation of survival on a population-based level.
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
Acta Oncologica 2013
11La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
Chemotherapy and Surgey ?
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Scopus -‐ HIPEC from 1985 -‐ Present: 886 document
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Scopus -‐ HIPEC and Gastric Cancer from 1980 -‐ Present : 296
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Ann of Surg Onc Jul 2007
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Author,year year Country N Med. surv Comparison Type study
Loggie, 2000 USA 22 10,1 case serie
Rossi, 2003 Italy 13 15 case serie
Hall, 2004 USA 34 11,2 vs 3,3 R0/1 vs R2 case serie
Glehen, 2004 France 49 21,3 vs 6,6 R0/1 vs R2 case serie
Scaringi, 2008 France 26 15 vs 3,9 R0/1 vs R2 case serie
Glehen, 2010 France 159 15 vs 5 R0/1 vs R2 case serie
Hultman, 2012 Sweden 10 17,1 vs 11,1 HIPEC vs sCTx match case control
Hultman, 2013 Sweden 18 19,1 vs 10,2 R0/1 vs R2 case serie
Magge, 20014 USA 23 9,5 case serie
Konigsrainer, 2014 Germany 18 8,9 vs 1,1 R0/1 vs R2 case serie
Rudloff, 2014 USA 16 11,3 vs 4,3 HIPEC vs sCTx RCT
Levine, 2014 USA 46 6,1 case serie
HIPEC in gastric cancer in Western Studies
16
Which PaXents may be considered for HIPEC treatment?
PaXents at high risk of development of PC: -‐ Serosal Invasion of Gastric Wall (Advanced T-‐Stage)
PaXents with occult peritoneal carcinomatosis : -‐ Posi?ve Cytology at Peritoneal Washing
PaXents with peritoneal carcinomatosis macroscopically evident
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Indipendent Risk Factors according to recurrent pa9ern by logisXc regression
BJS,2000
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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BJS,2002
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Median OS of paXents with CY1 with no macroscopic evident desease is similar to that of paXents with CY1 and gross metastaXc desease at laparoscopy
Ann Surg Onc, 2008
3y OS P0C1 is the same of P1C0
Lee S.D. et al, BJS, 2012
21
January, 2014
Mortality at 1 year
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Mortality at 2 year
F. Coccolini et al. / EJSO 40 (2014)
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Mortality at 3 year
F. Coccolini et al. / EJSO 40 (2014)
24
Mortality at 5 year
F. Coccolini et al. / EJSO 40 (2014)
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Which PaXents may be considered for HIPEC treatment?
PaXents at high risk of development of PC: -‐ Serosal Invasion of Gastric Wall (Advanced T-‐Stage)
PaXents with occult peritoneal carcinomatosis : -‐ Posi?ve Cytology at Peritoneal Washing
PaXents with peritoneal carcinomatosis macroscopically evident
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
26La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
Gastric Carcinomatosis
Randomisation
Cytoreduc?ve Surgery +
HIPEC with CDDP and MMC Cytoreduc?ve Surgery
27
Ann Surg Oncol (2011)
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Ann Surg Oncol (2011)
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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30La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
31La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Survival rates
1-‐year: 43%
3-‐year: 18%
5-‐ year: 13%
Disease-‐free survival rates 1-‐year: 31%
3 years: 12%
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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Glehen, Elias D., et al, 2010
34
2013
Grade 3–4 morbidity and mortality in series using
Common Terminology Criteria for Adverse Events (CTCAE)
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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O. Glehen, , Ann Surg Oncol (2010)
Mortality 10 paXents (6.5%)
Major complicaXons (grade 3–4 complicaXons) occurred in 38 paXents (27.8%)
Diges?ve fistula : 16% • Reopera?on: 14%
Mean post-‐operaXve stay : 24,2 ± 19 days
159 paXents from 15 insXtuXons
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
36La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
Morbidity
January, 2014
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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OUR EXPERIENCEVariables N° pts %
n° of cases 21
M/F 12/9
Median age (y) 60,52
Average PCI 3.33 ± 6.01 (range0 -‐ 19)
CC 0 18 85.71
CC 1 2 9.52
CC 2 1 4.77Neoadjuvant chemo 12 57.14
Adjuvant chemo 16 76.19Prophylactic HIPEC 12 57.14
Therapeutic HIPEC 9 42.86
Morbidity (grade I-‐II-‐III) 2 9.52
Morbidity (grade IV) 1 4.77
Mortality 1 4.77
38
5 y -‐ OS = 58 %5y-0S Stage III: 18%
5Y-OS Stage IV: 13%
Advances stages OS No HIPEC
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
Advances stages OS HIPEC
5y-0S : 58%
39La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
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“The patient is killed by what the surgeon doesn’t see” P.H.Sugarbaker
La Carcinosi Peritoneale : Indicazioni e Limiti del Trattamento HIPEC Prof. A Donini
Varese 13-‐03-‐15
CytoreducXve surgery and HIPEC should be considered as it is the only treatment that may offer long-‐term survival in paXents with gastric carcinomatosis
Which paXents? •Young paXents with very good general status ︎
•Possibility of complete cytoreducXve surgery (Only independant prognosXc factor )
•Limited carcinomatosis (PCI 12) PROPHYLACTIC HIPEC
Conclusion