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WCP symposium – Chirurgendagen – 22 mei 2014 Orde in de volgorde bij synchrone levermetastasen bij een colorectaal carcinoom Pieter Tanis, chirurg Academisch.

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Presentatie over: "WCP symposium – Chirurgendagen – 22 mei 2014 Orde in de volgorde bij synchrone levermetastasen bij een colorectaal carcinoom Pieter Tanis, chirurg Academisch."— Transcript van de presentatie:

1 WCP symposium – Chirurgendagen – 22 mei 2014 Orde in de volgorde bij synchrone levermetastasen bij een colorectaal carcinoom Pieter Tanis, chirurg Academisch Medisch Centrum, Amsterdam

2 WCP symposium – Chirurgendagen – 22 mei 2014 Mulitmodality treatment stage IV CRC Radiotherapy ChemotherapySurgery Synchronous CRCLM Cure Local ablation Stereotactic RTx SIRT

3 WCP symposium – Chirurgendagen – 22 mei 2014 Gereviseerde richtlijn colorectaal carcinoom 2014

4 WCP symposium – Chirurgendagen – 22 mei 2014 Gelijktijdig opereren van de primaire tumor en synchrone metastasen is geen standaard bij patiënten met synchrone levermetastasen. De werkgroep is van mening dat deze behandeling na zorgvuldige selectie in centra met veel ervaring op zowel colorectale chirurgie als leverchirurgie kan worden overwogen.

5 WCP symposium – Chirurgendagen – 22 mei 2014 Het medisch beleid bij synchrone levermetastasen en extrahepatische afwijkingen is niet eenduidig. Niveau 4: D Mening van de werkgroep Er zijn aanwijzingen dat overleving bij gelijktijdig opereren van primaire tumor en synchrone metastasen vergelijkbaar is met opereren van synchrone levermetastasen na 2 of 3 maanden. Niveau 3: C Yin 2013 (39); Li 2013 (26); Slesser 2013 (34) …..Timing is afhankelijk van expertise van het centrum.

6 WCP symposium – Chirurgendagen – 22 mei Geen perioperatieve chemotherapie bij resectabele metastasen 2.Inductiechemotherapie met targeted agent bij potentieel resectabele metastasen EORTC 40983; Nordlinger et al. Lancet Oncol 2013

7 WCP symposium – Chirurgendagen – 22 mei 2014 Level of evidence Only cohort studies Expert centers

8 WCP symposium – Chirurgendagen – 22 mei 2014 Multidisciplinary team discussion Individualize!

9 WCP symposium – Chirurgendagen – 22 mei 2014 Background Timing of multimodality treatment in stage IV CRC Biological behaviour of the tumour Loss of control at the primary site Loss of control at metastatic site(s) Treatment related toxicity –Preventing completion of treatment –Worsening physical condition / immune status leading to disease progression

10 WCP symposium – Chirurgendagen – 22 mei 2014 Biological behaviour prognostic implications of response to neo-adjuvant chemotherapy Adam Ann Surg 2004

11 WCP symposium – Chirurgendagen – 22 mei 2014 Biological behaviour Failure to complete 2-stage liver resection Chua JSO 2012

12 WCP symposium – Chirurgendagen – 22 mei 2014 Responses occur early……Toxicity occurs later Kishi et al. Ann Surg Oncol 2010 ) Induction chemotherapy

13 WCP symposium – Chirurgendagen – 22 mei 2014 Decision making Primary tumour characteristics –Right vs left sided / rectum –Symptomatic / asymptomatic –Locally advanced Type of liver metastases –Resectable vs potentially resectable –Minor (1-2 segments) vs major or complex resection –Requiring two-stage hepatectomy / PVE Patient condition / comorbidities

14 WCP symposium – Chirurgendagen – 22 mei 2014 Timing issues Timing of chemotherapy in curable CRC stage IV –Start of multimodality treatment (induction before synchronous resection) –In between treatment modalities (primary - metastatic surgery; metastatic - primary surgery; PVE – liver resection; RTx - surgery) Timing of radiotherapy in stage IV rectal cancer –Short vs long course –Before or after induction chemotherapy Timing of surgery for the primary tumour –Complicated primary (obstruction / perforation) –Simultaneous or staged resection Timing of surgery for metastases –Preceding primary tumour resection (‘reversed’ / ‘liver first’) –Multi-stage resections

15 WCP symposium – Chirurgendagen – 22 mei 2014 Vena porta embolisatie CAVE tumorgroei Fischer JAMA Surg 2013 Overlevingseffect onafhankelijk van resectabiliteit na PVE

16 WCP symposium – Chirurgendagen – 22 mei 2014 Implications of anastomotic leakage after LAR in stage IV N = 123 pts resected with curative intent Smith JD et al. Ann Surg Oncol Overall leak rate 6.5% 3y OS 72% 3y OS 32% Factors identified as significant in univariate analysis for Overall Survival (OS) Multivariate analysis for overall survival

17 WCP symposium – Chirurgendagen – 22 mei 2014 Traditional treatment resectable synchronous CRCLM adjuvant chemotherapy Resection primary CRC Resection LMRadiotherapy

18 WCP symposium – Chirurgendagen – 22 mei 2014 ‘Liver first’ approach advanced synchronous CRCLM (Fong score 3 or higher) Mentha BJS 2006 Mentha Dig Surg 2008 Resection primary CRC Liver first N=35 Induction Chemotherapy 3-6 courses Resection LM adjuvant chemotherapy N=9 two-stage hepatectomy with right PVE / PVL N=7 simultaneous resection N=5 not completed the programme 1 died of sepsis during chemotherapy 2 disease progression 1 rapid regrowth of LM, no rectal surgery RT N=13 primary rectal cancer RT for T3 and/or N+ stage

19 WCP symposium – Chirurgendagen – 22 mei 2014 Two-stage hepatectomy combined with primary tumour resection Karoui BJS 2010

20 WCP symposium – Chirurgendagen – 22 mei 2014 Treatment strategies for synchronous CRCLM the MD Anderson experience Interval chemotherapy (69%) Resection primary CRC Brouquet JACS 2010 Resection LM Classic N=72 Simultaneous N=43 Induction chemotherapy (26%) Resection primary CRC Combined resection of primary CRC and liver metastases Liver first (Reverse) N=27 Induction chemotherapy Resection LM RT Interval chemotherapy (59%) Livermetastases: median no. 3 (1-10), median max diameter 3 (1-10), bilobar 60% Livermetastases: median no. 2 (1-10), median max diameter 2 (1-12), bilobar 30% Livermetastases: median no. 3 (1-10), median max diameter 4 (2-11), bilobar 63%

21 WCP symposium – Chirurgendagen – 22 mei 2014 Treatment strategies for synchronous CRCLM the MD Anderson experience Bouquet JACS 2010

22 WCP symposium – Chirurgendagen – 22 mei 2014 Treatment strategies for synchronous CRCLM the MD Anderson experience Bouquet JACS 2010 Combined/ Simultaneous N=43 Classic N=72 Reverse / Liver first N=27 R0 resection primary 95%94%93% Resection >2 liver segments 35%66%89% RFA 9%33%19% R0 resection metastases 93%86%85% 90-day mortality5%3%4% Major complications 19%17%7% Adjuvant chemotherapy 77%64%78%

23 WCP symposium – Chirurgendagen – 22 mei 2014 Treatment strategies for synchronous CRCLM the MD Anderson experience Bouquet JACS 2010

24 WCP symposium – Chirurgendagen – 22 mei x5 Gy followed by chemotherapy Dutch M1 study 2x CAPOX + bevacizumab SCRT 5x5 Gy Surgery Rectum & liver / lung Van Dijk et al, Ann Oncol x CAPOX + 3x bevacizumab week Primary rectal cancer + synchronous resectable metastases in 1 or 2 organs Re-staging CT

25 WCP symposium – Chirurgendagen – 22 mei 2014 Dutch M1 study - interim results Conclusions Primary endpoint: radical resection and/or RFA of primary tumour and metastatic lesions in 72% –64 % 2-year recurrence –80% 2-year survival Locoregional control: –26% pCR –2/36 local recurrence at a median of 32 months Van Dijk et al, Ann Oncol 2013

26 WCP symposium – Chirurgendagen – 22 mei 2014 Induction chemotherapy first – rectal cancer Gall Colorectal Dis 2014 N=54 3-year OS 59%

27 WCP symposium – Chirurgendagen – 22 mei 2014

28 prognostic factors relevant for decision making Capussotti Ann Surg Oncol Number of metastases 2.Bulky primary tumor

29 WCP symposium – Chirurgendagen – 22 mei 2014 major hepatectomy

30 WCP symposium – Chirurgendagen – 22 mei 2014 Synchronous versus staged resection meta-analysis Lykoudis BJS 2014 ¶ = In favour of simultaneous Major hepatectomy series In favour of staged =primary first

31 WCP symposium – Chirurgendagen – 22 mei 2014 Synchronous versus staged resection meta-analysis The median MINORS score was 10, with incomplete follow-up and outcome reporting accounting primarily for low scores. Conclusion: None of the three surgical strategies for synchronous colorectal liver metastases appeared inferior to the others.

32 WCP symposium – Chirurgendagen – 22 mei 2014 Synchronous versus staged resection meta-analysis Intraoperative blood loss Colorectal Dis 2013

33 WCP symposium – Chirurgendagen – 22 mei 2014 Synchronous versus staged resection meta-analysis Hospital stay Colorectal Dis 2013

34 WCP symposium – Chirurgendagen – 22 mei 2014 Synchronous versus staged resection meta-analysis Overall complications Colorectal Dis 2013

35 WCP symposium – Chirurgendagen – 22 mei 2014 Synchronous versus staged resection meta-analysis Overall survival Disease free survival Colorectal Dis 2013

36 WCP symposium – Chirurgendagen – 22 mei 2014 Synchronous versus staged resection meta-analysis Selection criteria for patients undergoing simultaneous or delayed resections differs resulting in a discrepancy in the metastatic disease severity being compared between the two groups. The comparable intra-operative parameters, post-operative complications and survival found between the two groups suggest that delayed resections may result in better outcomes. Simultaneous resections can only be recommended in patients with limited hepatic disease until prospective studies comparing similar disease burdens between the two resection groups are available.

37 WCP symposium – Chirurgendagen – 22 mei 2014 Minimally invasive approaches Simultaneous laparoscopic approaches (near) pCR rectal primary –Local excision –‘Wait and see’ protocol

38 WCP symposium – Chirurgendagen – 22 mei 2014 One-stage total laparoscopic major hepatectomy + colorectal resection Ando Surg Today 2013 Spampinato Surg 2013

39 WCP symposium – Chirurgendagen – 22 mei 2014 Decision making Symptomatic primary Resection primary CRC (+minor liver resection) (laparoscopic) liver resection Radiotherapy / chemotherapy Decompressing stoma / stent Chemotherapy Simultaneous / staged resection Asymptomatic primary Major hepatectomy (>2 segments) Need for induction chemotherapy “Low risk” primary resection + minor hepatectomy (laparoscopic) simultaneous resection (laparoscopic) liver first approach Radiotherapy / chemotherapy

40 WCP symposium – Chirurgendagen – 22 mei 2014 Conclusies Orde in de volgorde van CRCLM Geindividualiseerd beleid Simultaan: ‘minor’ leverresectie met ‘laag risico’ primaire tumor Staged (‘liver first’): ‘major’ leverresectie / ‘hoog risico’ primaire tumor Inductie / interval chemotherapie ter voorkoming ziekteprogressie Meer mogelijkheden met laparoscopisch gecombineerde procedures / rectumsparende behandeling


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