PIPAC Training course Unit 1

Transcription

PIPAC:
Pressurized IntraPeritoneal Aerosol Chemotherapy
PD Dr. Martin Hübner
Médecin associé
Service de Chirurgie Viscérale
Centre Hospitalier Universitaire Vaudois
www.chirurgieviscerale.ch
Roadmap
Rationale for intraperitoneal chemotherapy
CHIP and
PIPAC:
Technique
Results
Limitations
Staging of peritoneal carcinomatosis
RECIST, imaging
Tumor markers
PCI
Biopsies
Staging
+
-
Tx response
+
Gold standard: laparoscopy+biopsies before and after tx
Treatment of advanced cancer
live longer
live better (QoL)
Few side effects
Costs?
initial treatment
Systemic treatment for PC
The Eindhoven experience
1995-2008: all patients with synchronous colorectal PC
≈ 13% overall colorectal
N=904
Klaver Ann Concol 2011
Systemic chemotherapy
for peritoneal carcinomatosis (PC)
median 66 weeks
Platinum-resistant situation
Live longer
live better (QoL)
side effects
costs
The ideal treatment for PC
Systemic HIPEC PIPAC
Efficacy
Administration of a large range of active molecules
Repetitive administration
Homogeneous drug distribution (peritoneal cavity)
Effective/deep drug penetration into tumor nodes
Potential for cure
No negative impact on QoL
Objective and early assessment of tumor response
Safety
Non- or minimally invasive
Low systemic drug uptake = low systemic toxicity
Low dose of drug = low local toxicity
No need for previous cytoreductive surgery
Feasibility
Applicable for most patients / few contraindications
Efficacy in the presence of diffuse small bowel invasion
Combination with systemic chemotherapy possible
X
X
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?
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X
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X
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X
-
?
-
X
na
?
X
X
X
X
?
X
?
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?
X
X
X
X
X
X
X
Peritoneal carcinomatosis
Locoregional disease
Relative Chemoresistance
Bad prognosis
Stage IV: all the same?
Characteristics
Liver
Lung
Chemo regimens
PC
N=364
non-PC
N=1731
=
63%
27%
=
=
82%
34%
=
Franco JCO 2012
Systemic chemo: PC vs. other
Franco JCO 2012
PC has worse prognosis
OS (months)
HR
PC
N=364
12.7
1.3 (1.2-1.5)
non-PC
N=1731
17.6
PFS (months)
HR
5.8
1.2 (1.1-1.3)
7.2
Consistent after adjustment for age, performance status, liver mets …
Franco JCO 2012
Peritoneum-plasma barrier
= problem for systemic chemotherapy
= friend of intraperitoneal administration
PIPAC: MA Reymond, DE GRUYTER 2014
The solution:
intraperitoneal treatment
Cytoreductive surgery, peritonectomy +
Hyperthermic Intraperitoneal Chemotherapy
Peritoneal carcinomatosis index
Complications
†
52
4.1%
Glehen Cancer 2010
Oncological outcome
Glehen Cancer 2010
Survival: independent predictors
Glehen Cancer 2010
Eligibility for CRS+HIPEC
HOTs
NOTs
detectable carcinomatosis
bowel obstruction
IV chemotherapy: ≥1 line
Rapid progression under
≥2 months systemic treatment
age <75 years
Refractory ascites
good performance: ECOG≤2 Extraabominal extension*
* except ≤3 easily resectable liver metastases
Elias Ann Surg 2011
… but there is always …
Fick’s law
homogenous distribution of gas molecules
Adolf Eugen Fick 1829-1901
Intraperitoneal pressure =
intratumoral platin concentration
A
B
C
D
IV
HIPEC PIPAC
Esquis Ann Surg 2006: rodent
Facy Ann Surg 2012: pig
The ideal approach:
Pressurized IntraPeritoneal Aerosol Chemotherapy
3 applications within 3 months
Reymond Surg Endoscopy 2000
Solass Ann Surg Oncol 2014
Systemic toxicity
Peak doxorubicin plasma concentrations
PIPAC: Doxorubicin 1,5 mg/m2 KOF, 30 min, 12mmHg
Solass Ann Surg Oncol 2014
Overview: efficacy and toxicity
Biodisponibility of chemotherapy (tumor nodules):
PIPAC > HIPEC > systemic
(animal model and human patient)
Pharmacokinetics: ↓ systemic drug concentration
Organ function
Liver: no relevant cytolysis, no metabolic/synthetic dysfunction.
Renal: normal range.
No cumulative toxicity!
Occupational health safety
Clinical outcomes:
wish = reality?
Results: the Herne experience
11‘11 – today: nearly 1000 procedures
Selection: Peritoneal carcinomatosis
Pretreated, platin-resistant
No indication for CRS + HIPEC
Non-access rate ≈ 15%
unpublished data, courtesy Prof. Reymond
Safety
Grade 1
Trocar hernia
0
Abdominal pain
53/53 (100%)
Bowel obstruction
0
Haemorrhage
0
Intraoperative bleeding
0
Cystitis
0
Urosepsis
0
Cardiac
6 (11%)
Neurological
1 (2%)
Renal
1 (2%)
Pulmonary
0
Inflammatory*
10 (19%)
Grade 2 Grade 3 Grade 4 Grade 5
0
0
0
0
0
1 (2%)
0
0
0
1 (2%)
5 (9%)
25 (47%)
2 (4%)
2 (4%)
1 (2%)
1 (2%)
1 (2%)
0
1 (2%)
0
0
0
0
0
0
ovarian
Tempfer 2015 Gynecologic Oncology
Quality of life
EORTC QLQ-30; GPH
ovarian
Tempfer 2015 Gynecologic Oncology
Efficacy: pathological response
29%
25%
21%
13%
12%
6388%
CR
PR
SD
PD
N/A
gastric
Summary: clinical results
N=
Access
PIPAC
CTCAE Efficacy Survival
≥2
3-5
Ovarian
64
83%
53% ≥3
17%
62-88%
+
Gastric
24
84%
71%
29%
63-88%
+
Colorectal
17
87%
76%
23%
64-84%
+
Mesothelioma
10
100%
80%
10%
60-75%
+
Feasible ≈ 70%
Efficace ≈ 75%
Safe ≈ 80%
QoL = ☺
HIPEC or PIPAC?
Carcinosis
CRS+
HIPEC
PIPAC
Indications for PIPAC
suggested
Colorectal
Isolated peritoneal
Peritoneal + limited other metastases
High risk for peritoneal carcinomatosis
2nd look after CRS+HIPEC
Gastric
Isolated peritoneal, palliative
Isolated peritoneal, neoadjuvant
Peritoneal + limited other metastases
High risk for peritoneal carcinomatosis
Ovarian
Platinum-resistant disease
Incomplete debulking, early 2nd look
Mesothelioma
Contraindication CRS+HIPEC
Pseudomyxoma
Contraindication CRS+HIPEC
to evaluate
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Acknowledgements
Chirurgie:
N Demartines, MA Reymond (D)
Oncology:
S Faivre, E Raymond, G Coukos,
T Boussaha, A Wolfer
Gynecology: P Mathevet, C Achtari
Anesthesia: M Cachemaille, C Blanc
… and all the others
martin.hubner@chuv.ch

PIPAC Training course Unit 1

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