Disclosures 1. None 2. Will only focus on resection as the liver - - PDF document

▶
disclosures
SMART_READER_LITE
LIVE PREVIEW

Disclosures 1. None 2. Will only focus on resection as the liver - - PDF document

Oct 31, 2022 245 likes •518 views

Colon Cancer Liver Metastases: Resection is the Goal Shishir K. Maithel, MD, FACS Assistant Professor of Surgery Division of Surgical Oncology Winship Cancer Institute Emory University Disclosures 1. None 2. Will only focus on resection as the

slide-1
SLIDE 1

1

Colon Cancer Liver Metastases: Resection is the Goal

Shishir K. Maithel, MD, FACS Assistant Professor of Surgery Division of Surgical Oncology Winship Cancer Institute Emory University

Disclosures

  • 1. None
  • 2. Will only focus on resection as the ‘liver

directed therapy of choice’

a) Hepatic arterial infusion therapy b) Ablation c) Trans-arterial Chemoembolization (TACE) d) Yttrium-90 Radioembolization e) SBRT

slide-2
SLIDE 2

2

RESECTABLE DISEASE Outline

  • Rationale for Surgery

– Risk stratification – Patient selection

  • Preoperative Chemotherapy

– Rationale – Morbidity – Duration of therapy – Disappearing lesions – EORTC trial

  • Clinical Strategy

– Metachronous – Synchronous

slide-3
SLIDE 3

3

RATIONALE FOR SURGERY Rationale for surgery

Natural history of unresected hepatic metastases

  • Wagner, et al (Mayo 1983)

Extent of liver mets 3 yr survival 5 yr survival Solitary (n=39) 21% 3% Multiple, one lobe (n=31) 6% 0% Widespread (n=182) 6% 2%

  • Wood, et al (Glasgow 1976)

Extent of liver mets 1 yr survival 3 yr survival Solitary (n=15) 60% 13% Multiple, one lobe (n=11) 27% 10% Widespread (n=87) 6% 0%

slide-4
SLIDE 4

4

Colucci et al. JCO 2005

5 yr Survival: 0%

Hepatic Resection for Colorectal Metastases

Study N Mortality% 5-yr Surv

Hughes, 1986 607 NS 33 Scheele, 1991 219 6 39 Rosen, 1992 280 4 25 Scheele, 1995 469 4 39 Nordlinger, 1995 1568 2 28 Jamison, 1997 280 4 27 Fong, 1999 1001 3 37 Abdalla, 2004 190 NS 58 Adam, 2006 2122 1.2 42

slide-5
SLIDE 5

5

Factors to Consider

  • Number of tumors
  • Size of tumors
  • Unilobar versus bilobar disease
  • Stage of primary cancer
  • Nodal status
  • Response to chemotherapy
  • Presence of extra-hepatic disease
  • Disease-free interval

Risk Stratification: Clinical Risk Score Colorectal Cancer Liver Metastases

Multivariate analysis, n=1001

  • Node (+) colorectal primary
  • Disease-free interval < 1 year
  • More than 1 hepatic tumor
  • Largest hepatic tumor > 5 cm
  • CEA > 200 ng/mL

1 point for each criterion Clinical risk score = sum (0-5)

Fong et al. Ann Surg 1999

slide-6
SLIDE 6

6

Clinical Risk Score (CRS)

Survival Score 1-yr 3-yr 5-yr Median(mos) 93% 72% 60% 74 1 91% 66% 44% 51 2 89% 60% 40% 47 3 86% 42% 20% 33 4 70% 38% 25% 20 5 71% 27% 14% 22

Clinical risk score predicts survival after resection, n=1001

Fong et al. Ann Surg 1999

10 yr Survival Stratified by CRS

60 120 180 240 0.0 0.2 0.4 0.6 0.8 1.0

CRS

1 2 3 4 5

months proportion surviving

Low CRS n = 359 High CRS n = 161

Tomlinson et al. J Clin Onc 2007

slide-7
SLIDE 7

7

10-year survival (n=612)

What precludes long term survival?

5% 11% 16% 23%

≥ 4 metastases

0% 9% 10% 20%

Margin Positive

35% 41% 41% 53%

Size of hepatic met>5cm

39% 32% 51% 59%

# of hepatic mets >1

36% 36% 46% 51%

DFI < 12mos

7% 8% 11% 16%

Preop CEA > 200

50% 52% 56% 63%

Node positive primary %

7% 5% 11% 13%

Synchronous Dz (%)

68% 62% 63% 63%

Resection: ≥ Lobectomy

<2yr Survival 2-5yr Survival 5-10yr Survival >10yr Survival

Tomlinson et al. J Clin Onc 2007

Partial Hepatectomy is Potentially Curative

Years Proportion surviving

15 10 5 1.0 .8 .6 .4 .2

Median Survival 44mos >10 yr ≈ CURE n=102 5-10 yr 2-5yr <2yr 1985 – 94 n = 612 with 10 yr FU Tomlinson et al. JCO 2007

slide-8
SLIDE 8

8

Shift in Perspective

Surgery is not an adjunct to Chemotherapy

Chemotherapy is an adjunct to Surgery

CHEMOTHERAPY

slide-9
SLIDE 9

9

Preoperative Chemotherapy

  • Rationale

– Eradicate microscopic disease prior to resection – Allows determination of effectiveness of chosen regimen – Time delay to surgery allows declaration of

  • ccult disease (biologic selection)
  • Identify patients who progress

– Patients will not tolerate chemo after surgery

  • Considerations

– Toxicity (patient and hepatic) – Duration of therapy – Disappearing lesions

Adam R et al. Ann Surg 2010

slide-10
SLIDE 10

10

Adam R et al. Ann Surg 2010 No Preop Chemo Preop Chemo

No Difference in Survival

Postop Chemo did NOT influence OS or DFS in patients with tumors < 5 cm in size

Adam R et al. Ann Surg 2010

Identical Recurrence Pattern

slide-11
SLIDE 11

11

Adam R et al. Ann Surg 2004 Blazer DG, Vauthey JN et al. JCO 2008

slide-12
SLIDE 12

12

Gallagher DJ, Kemeny N et al. Ann Surg Onc 2009 Carpizo DR, D’Angelica M et al. Ann Surg Onc 2009

slide-13
SLIDE 13

13

Carpizo DR, D’Angelica M et al. Ann Surg Onc 2009

CHEMOTHERAPY TOXICITY

slide-14
SLIDE 14

14

Overman MJ et al. JCO 2010

Oxaliplatin Toxicity

Sinusoidal Obstruction Portal Hypertension Thrombocytopenia Splenomegaly

Rubbia-Brandt L et al. Ann of Oncology 2004

slide-15
SLIDE 15

15

Vauthey JN et al. JCO 2006

No Preop Chemo Preop Oxaliplatin Postop Complication 18.3% 26.5% Major Complication 9.5% 15.1%

Vauthey JN et al. JCO 2006

No Steatohepatitis Steatohepatitis 90-Day Mortality 1.6% 14.7% Death from postop liver failure 0.8% 5.8%

slide-16
SLIDE 16

16

Neoadjuvant Chemotherapy

  • Study design

– 67 patients

  • Major liver resection for colorectal metastases (≥ 3

segments)

  • 45 (67%) had neoadjuvant chemotherapy
  • 22 (33%) no preoperative therapy

– Chemotherapeutic agents

  • FOLFOX

FOLFIRI

Karoui M et al. Ann Surg 2006; 243(1): 1-7

Neoadjuvant Chemotherapy

  • Results

– No difference in preoperative characteristics

Karoui M et al. Ann Surg 2006; 243(1): 1-7

slide-17
SLIDE 17

17

Neoadjuvant Chemotherapy

  • Results

– No difference in intra-

  • perative

characteristics

Karoui M et al. Ann Surg 2006; 243(1): 1-7

Neoadjuvant Chemotherapy

  • Results

– Increased morbidity in chemotherapy group

Karoui M et al. Ann Surg 2006; 243(1): 1-7

slide-18
SLIDE 18

18

Neoadjuvant Chemotherapy Duration

White, Kemeny et al. J. Surg Onc 2008

Minimal change in tumor response in the 4 – 6 month interval

White, Kemeny et al. J. Surg Onc 2008

Minimal change in tumor response in the 4 – 6 month interval

Neoadjuvant Chemotherapy Duration

slide-19
SLIDE 19

19

Complete Response (CR) after Chemotherapy: Does it mean cure?

  • 586 patients treated
  • 38 patients with CR of at least 1 lesion
  • 66 sites disappeared on imaging
  • Surgery 4 weeks after imaging

Benoist S et al. JCO 24(24) 2006

66 Sites with CR

Radiologic Response Does NOT Equal Pathologic Response

20 sites seen at surgery 46 sites no lesion found 15 sites resected 31 sites left in place 12 (80%) viable tumor cells In situ recurrence in 23 (74%) 55/66 (83%) not cured

Benoist S et al. JCO 24(24) 2006

slide-20
SLIDE 20

20

mCRC with Liver

  • nly Metastases

(up to 4 lesions) (N=364) Chemo  Surg  Chemo (n=182) R A N D O M I Z A T I O N Endpoint 3-yr PFS Surgery (n=182) Nordlinger et al. Lancet 2008 Chemotherapy = FOLFOX4 X 6 cycles before and after surgery

Progression Free Survival

Nordlinger et al. Lancet 2008 Chemo + Surgery Surgery alone

slide-21
SLIDE 21

21

Details of the EORTC Trial

  • Not a trial of preoperative vs postoperative

chemotherapy

  • Only 7% progressed on preoperative

chemotherapy

  • 36 patients not given postoperative

chemotherapy

– 6 patients: toxic effects from preop chemo – 8 patients: perioperative complications

Nordlinger et al. Lancet 2008

Details of the EORTC Trial

  • 7.3% improvement in 3-yr PFS

– 6% difference in unresectability rate (4% vs 10%) – 1 patient not resected due to liver damage from chemotherapy – Survival curves remain parallel after time point of resection

  • No difference in OS at 8-year follow up

Nordlinger et al. Lancet 2008

Preop Chemo Surgery Postop Complications 25% 16% Preop Chemo Surgery 3-yr PFS 35.4% 28.1%

slide-22
SLIDE 22

22

CLINICAL STRATEGY METACHRONOUS

Resectable Disease Resection Postoperative Chemotherapy Preoperative Chemotherapy (limited duration

  • f 2 months)

Resection Postoperative Chemotherapy Low CRS (≤ 2) High CRS (> 2)

slide-23
SLIDE 23

23

CLINICAL STRATEGY SYNCHRONOUS Asymptomatic Primary Lesion

Poultsides et al. JCO 2009

slide-24
SLIDE 24

24

  • Study design

– 240 patients with synchronous metastases – Retrospective review

  • Sep 1984 – Nov 2001
  • Results

– Group I: 134 patients with simultaneous resection

  • Small and fewer liver metastases
  • Less extensive liver resection

– Group II: 106 patients with staged resection

Blumgart L et al. JACS 2003

Simultaneous Resection

  • Results

– Postoperative outcomes

  • Fewer complications in Group I

– 49% versus 67%

  • Decreased hospital stay (10 versus 18 days)
  • No difference in perioperative mortality (< 3%)
  • Conclusions

– Simultaneous resection is safe and efficient in selected patients

Simultaneous Resection

Blumgart L et al. JACS 2003

slide-25
SLIDE 25

25

Resectable Disease Resection (Simultaneous or Staged) Chemotherapy (limited duration

  • f 2 months)

Preoperative Chemotherapy (limited duration

  • f 2 months)

Resection (Primary ± Liver) Postoperative Chemotherapy Symptomatic Asymptomatic Liver Resection Postoperative Chemotherapy

Conclusions

  • Patient selection is key
  • Complete resection is the goal
  • Perioperative chemotherapy is individualized
slide-26
SLIDE 26

26

Colon Cancer Liver Metastases: Resection is the Goal

Shishir K. Maithel, MD FACS Assistant Professor of Surgery Division of Surgical Oncology Winship Cancer Institute Emory University

August 10, 2014