THE SAFETY , FEASIBILITY, ONCOLOGICAL OUT COME OF LIVER FIRST APPROACH FOR LIVER METASTASIS IN COLO RECTAL TUMOR

1. Liver first approach for CRLM
Dr . Mutaz al makhamrah
Surgical oncology fellow
KHCC
Surgical oncology department

2. • Liver first approach also-called reverse treatment of advanced
synchronous colorectal liver metastases
• (ASCRLM).
• a highly effective neoadjuvant chemotherapy directed against the
liver metastases is given first, liver surgery is done next, and the
colorectal resection is performed last.
• The rationale of such a strategy is to control the CRLM at the same
time as the colorectal primary, optimize the chances of a curative liver
resection.
Introduction

3. • The liver-first approach was first described by Mentha et al. in 2008.
• a total of 30 patients have undergone all phases of the program
• (neoadjuvant chemotherapy , liver surgical clearance, pelvic radiotherapy if indicated and
removal of the primary tumour, in that order).

4. • Overall survival rates of the30 patients who completed the program at 1, 2, 3, 4 and 5years were 100, 89, 60, 44
and 31%.

5. • Is the liver first approach feasible??
• perioperative morbidity and mortality rates!!
• Oncological out come !!

6. • Outcomes of patients who underwent a liver-first approach for CRLM between 2005 and 2015 were
retrospectively evaluated from a prospective database.
• In 92 of these patients, a liver-first approach had been planned

7. postoperative morbidity and mortality were 31.5% and 3.3% following liver resection and 30.9% and 0% after
colorectal
surgery, respectively.

8. • Between January 2009 and April 2013,18 synchronous colorectal liver metastases (sCRLMs)
patients with a planned liver-first approach in the Hepatopancreatobiliary Surgery Department Ⅰ of the
Beijing Cancer Hospital were enrolled in this study.
• Clinical data, surgical outcomes, morbidity and mortality
rates were collected.
The feasibility and long-term outcomes of the approach were retrospectively analysed.

12. • At the time of the last follow-up, 16 (88.9%)
patients completed a curative paradigm.
• The median follow-up was 30 months (range:
12-43; mean: 30.54).
• The 1 and 3 year overall survival rates were
94.4% and 44.8%, respectively
• The median disease free survival after surgery
was 11 months (range: 1-40; mean: 13.4).
After the hepatic resection,
• 16 patients had a recurrence during the follow-
up.
• The patterns of recurrence were intrahepatic
only (10, 62.5%) and combined intra and
extrahepatic (6, 37.5%).’
• These surgical outcomes were comparable with
other results associated with the liver-first
approach

13. • A literature search of databases (MEDLINE and EMBASE) to identify published studies of LFA in patients
with colorectal cancer and synchronous CLM was undertaken focussing on the peri-operative regimens of
LFA and survival outcomes.
• Three observational studies and one retrospective cohort study were included for review.
• A total of 121 patients with colorectal cancer and synchronous CLM were selected for LFA.

14. Flow chart showing the search strategy used to identify
studies

18. • prospectively registered data from two nationwide registries.
• Clinical, pathological and survival outcomes were compared between the liver-first strategy and
the classical strategy (2008–2015), Overall survival was calculated.
• A total of 623 patients were identified, of which 246 were treated with the liver-first strategy
and 377 with the classical strategy.

19. Characteristics of resected patients with primary rectal cancerCharacteristics of resected patients with primary colon cancer

20. • The median follow-up time was 40 (27–57) months. No difference in overall survival was found (P = 0.344),
with an overall five-year survival of 54% for the classical group and 49% for the liver-first group.

21. • Systematic review, pairwise meta-analysis and network meta- analysis were performed.
• The primary and secondary outcomes were5-year overall survival and postoperative major morbidity,
respectively.
• No significant differences in long-term survival and major morbidity were found amongst the three
approaches.
• The hazard ratios(95% confidence interval) for 5-year overall survival for the simultaneous, delayed and
liver-first approaches were 0.93 (0.69 - 1.24, P = 0.613), 0.97 (0.87 - 1.07, P = 0.596) and 0.90 (0.67 -
1.22, P = 0.499),respectively.

22. • the liver-first approach with a
surface under the cumulative
ranking area score of 89% was
ranked as the potentially best
treatment option based on
probabilities of treatment ranking.
• The SUCRA score expresses the percentage of
effectiveness or safety of each treatment as compared
with that of an “ideal” treatment that always rank first

23. • Several arguments have been posited against upfront colorectal resection:
• (i) over the past decade, peri-operative chemotherapy followed by a hepatic resection is increasingly
performed in patients with resectable CLM. modern chemotherapy regimens has produced better
response rates with a partial response rate up to 50% and a median survival approaching 2 years in
patients with unresectable metastatic colorectal cancer(Cassidy J et al2000)
• (ii) recent studies demonstrated that colorectal cancer resection in patients with metastatic
colorectal cancer was associated with a significantly higher 30-day mortality of 10% when compared
with a colorectal cancer resection in the non-metastatic settingTemple. Schrag D et al. (2004,Ho YH et al. (2011)
• (iii) the potential colonic complications of leaving the colorectal cancer intact may have been
overstated. The rate of surgical intervention for colonic complications was only 20% in one review of
255 patients with metastatic colorectal cancer treated primarily with 5-FU. Poultsides et al
Conclusion

24. • (iv) even if patients develop symptoms related to advanced colorectal cancer, endoscopic
treatment has been increasingly used.
• (v) an anastomotic leak after colorectal resection is not uncommon. The rate of an anastomotic
leak after a rectal resection in particular was up to 12%,with a morbidity rate of up to 50%. Such
complications could lead to a delay or even cancellation of both hepatic surgery and
chemotherapy.
• (vi) metastatic disease rather than primary colorectal cancer has been proposed to be the main
determinant of patient survival and thus treatment of the CLM should be the first priority.
• the optimal sequence of liver surgery, colonic resection and systemic chemotherapy in
synchronous CLM is as yet unresolved.
• Consideration should be give in particular to liver damage owing to chemotherapy in the form of
steohepatitis (associated with irinotecan exposure) and sinusoidal injury (linked to oxaliplatin
administration), This may increase the risk of liver failure after a resection.