Colorectal Peritoneal Carcinomatosis Patient …...Colorectal Peritoneal Carcinomatosis Patient...
Transcript of Colorectal Peritoneal Carcinomatosis Patient …...Colorectal Peritoneal Carcinomatosis Patient...
Colorectal Peritoneal CarcinomatosisPatient selection for CRS+HIPEC
A D’Hoore MD PhD, AM Wolthuis MD PhD, G.Bislenghi MDE Van Cutsem, S Tejpar, J Dekervel
RC Dresen, V Vandecaveye
Department of Abdominal Surgery, Digestive Oncology and Radiology
No related disclosures
Franko J et al. Lancet Oncology 2016
Oligometastasis in spectrum concept
- Unique group of patientslimited burden of metastatic disease
- Ablative therapy of the metastases in combination with systemic therapycould lead to
prolonged disease - free survival and even cure
Treatment strategy
Limited peritoneal spread eligible for locoregional treatment in combination with systemictreatment
Two components
HIPEC
Complete cytoreductiveSurgery
Prodige 7 : patients’ outcome depends on our capacity to obtain a macroscopically complete resection
Prospective comparative trial
Elias D etal. J Clin Oncol 2008; 27
Median survival : 23.9 mo (standard) vs 62.7 mo (HIPEC) p<.055 year overall survival rates : 13% (standard) vs 51% (HIPEC)
No ∆ systemic CHT : mean 2.3 lines
A systematic review and meta-analysisCRS + HIPEC
Huang CQ-Oncotarget 2017
15 controlled studies 76 HIPEC related studies
Cytoreductive surgery = standardised- Extraperitoneal resection
- Diaphragma stripping
- Radical omentectomy
- …
HIPEC modalities: heterogeneity in protocols- Different chemotherapeutic drugs
Mitomycin C – Oxaliplatin
- Carrier solution- Perfusate Volume- Open versus closed technique- Duration of the perfusion
Impact on Pk and Pd of the drug
Leuven prospective HIPEC database
Selection
Resectability : complete cytoreductive surgery ?- accuracy whole-body DW MRI
Role of ‘neoadjuvant’ systemic chemotherapy- improve patient selection for CRS- borderline resectable/unresectable disease
Systemic disease a (relative) contra-indication
Quantitative intra-operative assessmentPeritoneal Carcinomatosis Index (P Sugarbaker)
Simplified PCI 7-region count(Dutch Cancer Institute) (Dutch Cancer Institute)
Jacquet P. et al. Cancer treat Res 1996; 82:359-74Verwaal VJ et al. Br J Surg 2004; 91:739-746
extent of disease relates toability of obtaining complete cytoreduction
Eur J Surg Oncol 2008
Median survival (mo)
0
5
10
15
20
25
30
35
40
45
50
Loggie Glehen Verwaal Yan
CC-0
CC-1
CC-2
Optimised Chemomedian survival : 2
extensive disease : radix infiltration apparently limited disease
Role of laparoscopy-Obviate unnecessary laparotomy (20%)
- extensive small bowel involvement- extensive diaphragm involvement
-Understages Resectable disease
- coeliac axis and hepatic pedicle- retroperitoneal extension
-Hampered by previous laparotomy/adhesions
Whole-body DW MRI for operability assessment
DresenRC et al. Cancer Imaging 2019
97.8% sensitivity to detect PC
88.9% PPV; 98.7% NPV
Exclude patients with extensive small bowel disease
Retroportal N+
N+P+
P+
Primary
Kruckenberg
Leuven data (60 patients)
distant/nodal metastases : 18 of patients had unresectable distant metastases WB-DWI detected in 17 of 18 (94%).
Correct assessment of operability in 54 of 60 patients (90%)
Understaging extent disease 6 ptsNo overestimation of PCI
Only laparoscopy in 16 patients
Whole body MR-DWI based PCI versus PCI at laparotomy
N = 42Linear correlation : R2 = 0,84p < 0.0001
* WB-DWI - 5 underestimated3 evaluated by laparoscopy2 Futile attempt of surgery
* No erroneous overestimation of disease
22
2
1 2
2
0
0
0
0 2
0PCI = 11Operable
0
Patient 56 years old.
3.5 years after primary treatment of T3N1 SigmoidCa
Treated with neo-adjuvant chemotherapyfor peritoneal carcinomatosis
FDG-PET CT shows excellent response withregression of peritoneal metastasesand no distant metastases
CEA level significantly decreased
Eligible for HIPEC?
33
2
1
2
2
21
1
3 3
11PCI = 24Inoperable
Resectability (complete cytoreductive )
T biology
Adapted from ESMO guidelines , Ann of Oncol 2016.
Bad
Good
easy difficult
PCI < 12Limited small
bowelWell,mod
differentiation, Node -
PCI > 15Extensive small bowel involvementHepatic hilum involvement
Non-differentiatedSignet-cellExtensive nodal diseaseRapid progression under systemic therapyBRAF mutation
patient-relatedBiological age - significant comorbidity
overall median survival = 29 mo
P<.001
multivariate analysis of overall survival
HR 95%CI p
Well/moderate differentiation 4.011 1.024- 8.826 0.045
Complete cytoreduction 5.152 1.185-10.179 0.023
Yan TD et al. Ann Surg 2008; 248:829-835
Prognosis of metastatic colorectal cancer is affectedboth by number of disease sites and presence of peritoneal involvement
liver M+ and PC : median survival 5 moa more aggressive strategy for selected patients ?
Thomassen I. et al.Dis Colon Rectum 2013
PC and limited resectable liver M+ ?any better than systemic chemotherapy ?
PDSS peritoneal disease severity score
Ann Surg Oncol 2016
COMPASS nomogram
PDSS COMPASS
External validation of COMPASS
Demey K, Wolthuis A, de Buck van Overstraeten A, Fieuws S, Vandecaveye V, Van Cutsem E, D'Hoore A.Ann Surg Oncol. 2017 Nov;24(12):3604-3608
RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity ScoreAnn Surg Oncol 2019
Ongoing Clinical Research
1. Role of prophylactic HIPEC in high risk advanced CR cancerpT4aperforated tumorsKrukenberg
2. Induction chemotherapy before debulking surgery
Risk for PC in deep serosal involvement and T4a
159 T4 colorectal cancer patients
Synchronous PC n=29
Synchronous distant
metastases, other than PC:
n=11
No Synchronous PC n=130
Metachronous PC n=30
Disease (recurrence)
other than PC at time of
diagnosis of PC: n=18
Peritoneal disease T3 (<1mm) T4aAt the time of surgery
9.3% 22% 0.076
Subsequent 13% 28% 0.069
p T4a
pT3 ≤ 1 mm
Klaver C et al. Ann of Surg Oncology 2018
Advantages of induction systemic treatment
- 50 % systemic relapse
- further selection
progression under chemo/beva : excludes CRS + HIPEC
- Increase resectability ?
Role of ‘neoadjuvant’ chemotherapy in unresectable disease
Pilot study
N = 10 patients
laparoscopic mapping (7 regions)
start systemic chemotherapy : Folfox + Beva
results : 1 pt. developped small bowel perforation : palliative treatment
7 pts. progressive disease
only 2 : stable diseasemedian overall survival 8.3 mo (1.4-16.8)
Hompes D. et al. Colorectal Dis 2014
Conclusion
Patients with limited PC from colorectal origin shouldundergo complete cytoreductive surgery (+ HIPEC)
but HIPEC protocol needs standardisation
pT4a (and deep serosal invasion) tumours need intensifiedfollow-up (Whole Body-DW MRI)
prophylactic HIPEC = investigational