Management Algorithms for Primary and Metastatic Liver Cancer

Transcription

1 Management Algorithms for Primary and Metastatic Liver Cancer Chief, Division of Surgical Oncology Head Hepatobiliary & Pancreatic Surgery City of Hope Comprehensive Cancer Center

2 Cancer statistics, 2018, Volume: 68, Issue: 1, Pages: 7-30, First published: 04 January 2018, DOI: ( /caac.21442)

3 Less than 10% of HCC arises in normal liver More than 80% of HCC is associated with liver cirrhosis from Hepatitis B and C 90% 10% Other risk factors: Hemochromatosis, Alcoholic liver disease, Tyrosinosis, Aflatoxin (Africa), Vinyl Polymer, NASH HCC is present in 20-40% of patients with cirrhosis and HBV and HCV at autopsy

4 Ascites Umbilical Hernia Hematemesis Melena / Bleeding per rectum Muscle Wasting Hypoalbuminemia Encephalopathy

5 Most patients with HCC die from liver failure (15-20% Mortality) HCC is multicentric in >80% of patients with cirrhosis

6 Primary Tumor TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Solitary tumor 2 cm or less in greatest dimension without vascular invasion T2 Solitary tumor 2 cm or less in greatest dimension with vascular invasion, or Multiple tumors limited to one lobe, none more than 2 cm in greatest dimension, without vascular invasion, or A solitary tumor more than 2 cm in greatest dimension without vascular invasion T3 Solitary tumor more than 2 cm in greatest dimension with vascular invasion, or Multiple tumors limited to one lobe, none more than 2 cm in greatest dimension, with vascular invasion, or Multiple tumors limited to one lobe, any more than 2 cm in greatest dimension, with or without vascular invasion T4 Multiple tumors in more than one lobe, or tumor involves a major branch of portal or hepatic veins Lymph Node Involvement NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis Distant Metastasis MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis STAGE GROUPING Stage I T1, N0, M0 Stage II T2, N0, M0 Stage III T1, N1, M0 T2, N1, M0 T3, N0, M0 T3, N0, M0 Stage IVA T4, any N, M0 Stage IVB Any T, any N, M1

7 CHILDS Classification Ascites None Easily controlled Poorly controlled Albumin > <3.0 Bilirubin < >3.0 Encephalopathy None Mild Advanced Nutritional Status Excellent Good Poor Modified CHILD-PUGH Classification Ascites None Controlled medically Poorly controlled Albumin > <2.8 Bilirubin < >3.0 Encephalopathy None Controlled medically Poorly controlled INR < >2.25 Childs A: 5-7 pnts Childs B: 8-10 points Childs C: points

8 MILAN CRITERIA 1 UCSF CRITERIA 2 Solitary lesion 5 cm or 3 lesions none > 3 cm Solitary lesion 6.5 cm or 3 lesions none > 4.5 cm and total tumor diameter 8 cm MELD Score R = (0.957 X log e (creatinine mg/dl) X log e [total bilirubin mg/dl] X log e [INR] ) X 10 (1) Mazzaferro et. al. N Engl J Med 1996; 334: (2) Yao et.al. Hepatology 2001;33:

9 Metabolic 4% Fulminant 6% PSC 11% Other 2% Hep C 24% PBC 12% Hep B 7% Cryptogenic 13% Alcohol 21%

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11 1967

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14 1981: Didier Houssin & Henri Bismuth- First Reduced Size Liver Graft 1987: Rudolf Pichlmayer- First Split Liver Transplantation Gridelli, B. (2013). Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro

15 Living Donor Liver- Dissection & Transection Truly a pleasure

16 Duct- Duct Roux-en-Y

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18 Colon & Rectal Cancer 140, 000 New Cases 20-30% Synchronous Liver Mets 70-80% No Liver Mets 25% Liver Mets Untreated <1% Alive 5 yrs Resected 60% Alive 5 yr

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22 Greek Mythology- Prometheus Prometheus had stolen fire from Zeus and given it to the mortals in their dark caves. He had Hepheistos shackle Prometheus to the side of a crag, high in the Caucasus mountains. Each day, Prometheus would be tormented by Zeus eagle as it tore at his immortal flesh and tried to devour his liver. Each night, as the frost bit it s way into his sleep, the torn flesh would mend so the eagle could begin anew at the first touch of Dawn.

23 Challenges of Liver Surgery Anatomical Challenges No Bloodless plane exists It s deceptive surface anatomy leads into rather than away from the its largest vessels Complex inflow and outflow tracts cross at right angles Metabolic- Post Chemo Histologic Simplicity belies its Metabolic Complexity It has been one of the last organs to yield to the rapid surgical advances made in the 19 th century

24 Claude Couinaud working with his collection of liver casts

25 RP RA 7m

26 CT Scan is always Good- BUT Nothing like a great MRI with EOVIST PET is meaningless for Anatomic Imaging- Great for Extrahepatic Disease

27 Intra-op Ultrasonography detects 25-35% more lesions than CT, MRI and Transabdominal US Now the Standard of Care- However MRI Better

28 1. Surgery 2. Chemotherapy 3. Microwave Ablation/ Radiofrequency Ablation 4. Irreversible Electroporation (NanoKnife) 5. Hepatic Artery Infusion Pump 6. Radiation/ Radioembolization (SIRT) 7. Cryotherapy 8. Ethanol Injection 9. Transplant 10. Gene Therapy

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30 RF ablation- alternating electric current in the radio-frequency range ( khz) Ionic agitation causes frictional heat, thermal injury Spherical Ablation Area up to 7cm Temperatures raised above 90 C (well above the C necessary to destroy tissue.) Percutaneous, Laparoscopic, or Open Approach Microwaves to induce an ultra-high-speed (2450 MHz) alternating electric field Rotation of water molecules Thermal coagulation of tissue Excellent role for mets < 3 cm

31 Reversible Electroporation Irreversible Electroporation Irreversible electroporation (IRE) is a way to increase cell membrane permeability by subjecting it to an electrical field that leads to cell death in soft tissue lesions. It does this by opening permanent, nano-sized pores in the membranes of the lesion s cells. This irreversible damage causes natural cell death.

32 Post-chemo liver is SICK Different Beast Friable Oozy Steatotic Steatohepatitis Sinusoidal Obstruction

33 Schoellhammer HF, Singh G, Leong L. J Natl Compr Canc Netw Sep;11 Suppl 4:S3-8. PMID:

34 Guye ML, Schoellhammer HF, Chiu LW, Kim J, Lai L, Singh G. In J Surg Oncol Dec; 4(4):

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36 ALPPS- Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy 40%-80% within 6-9 days ALPPS- Hypertropy of FLR 8%-27% within 2-60 days PVL/PVE- Hypertropy of FLR 9 Days Later Operative morbidity 16%-64% Mortality 12%-23% Int J Surg. 2014;12(5): doi: /j.ijsu Epub2014 Apr 2.

37 Feb 21 st 2012

38 SS Feb 21 st 2012

39 NCCN Recommendations (2017 Condensed) First Line Second Line 3 rd or 4 th Line 4 th or 5 th Line FOLFOX or FOLFIRI + anti-egfr Alternate chemo +/-anti-angiogenic TAS-102 or Regorafenib RAS-WT Left Colon Treat like 1 st Line RAS-MT Chemo +antiangiogenic FOLFIRI or Irinotecan + Anti- EGFR FOLFIRI or irinotecan + anti- EGFR or ant-egfr TAS-102 or regorafenib TAS-102 or regorafenib MCRC FOLFOX or FOLFIRI or XELOX+/- BEV Alternate chemo +/- antiangiogenics TAS-102 or regorafenib RAS-MT or Right colon with RAS- WT FOLFOXIRI +/- BEV CAP+/- BEV TAS-102 or regorafenib FOLFOX or CAPOX or FOLFIR +/-antiangiogenic Right colon: consider anti- EGFR only 2 nd line and beyond Alternate Chemo TAS-102 or Regorafenib 5-FU +/- BEV FOLFOX or CAPOX or FOLFIRI +/- antiangiogenic Alternate Chemo TAS-102 or regorafenib For MSI-H patients consider pembrolizumab or nivolumab for second line and beyond or 1 st line poor PS

40 Apr 13 th 2012

41 SS June 28 th 2012 C A B Surgery : discharged POD 8 Right Hemicolectomy A: Right Posterior Sectionectomy (Seg 6 & 7) B: Wedge Resection of Seg 4B/ 5 lesion..sitting right on the portal vein. So basically enucleated..no attempt at getting margins C: Wedge Resection of lesions in Seg 2 and 4A. No attempt at getting margins.as this was sitting on the bifurcation of the left hepatic vein. Bed Nanoknifed (Irreversible Electroporation). Grossly all tumor removed.

42 SS Mar 19 th 2018 Schoellhammer HF,., Gagandeep S. BMC Cancer 2015, 15:271.

43 Surgery Chemotherapy Resectable 10% Unresectable 90% 5yr Survival: >60% 5yr Survival: 1-2% 2 Worlds ignoring each other

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45 Anti-Angiogenesis Ramucirumab Regorafenib Aflibercept Anti-EGFR Bevacizumab Panitumumab 2004 Cetuximab TAS-102 Cytotoxics Oxaliplatin Capecitabine 1996 Irinotecan 1960 s 5-Fluorouracil

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47 Stump of Right Hepatic Vein IVC Stump of Rt. Portal Vein

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50 Dec 13 th, 2006

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54 Johns Hopkins Europe John Hopkins: Annals of Surgery. 235(6):759-66

55 Margins are an indicator and NOT a governor of prognosis N= 557 Univariate Analysis 49.6 m Scheele J et al. Surg Onc Clin N Amer; 2003; 12: Pawlik et al. Annals of Surgery: 241: , 2005

56 Japanese Experience Hepatic LN+ does NOT matter- Resect Celiac LN + Maybe/ Maybe Not > 4 LN+ the Survival adv is lost CEA levels matter SIZE does NOT matter (3 or >6cm) Wedge Res = Anatomic Resections Adjuvant Chemo is a must HAI does NOT offer any advantage John Hopkins: Annals of Surgery. 235(6):759-66, 2002 Japanese Multicenter Study: Dis Col & Rec: 46: S22-31, 2003

57 HAI Better response rate for multiple colorectal liver mets

58 HAI = Systemic Chemo ( ) Results showed no evidence of an advantage in progression-free survival or overall survival for the IHA group; Thus continued use of this regimen cannot be recommended outside of a clinical trial Volume 361, Issue 9355, 1 February 2003, Pages

59 Survival data available for 344 patients (98.6%) Liver Resection Synchronous with Hepatic Arterial Infusion Pump (HAIP) for Colorectal Cancer Liver Metastases: Results alone or with Liver Resection. I. Konstantinidis..G. Singh. Regional Cancer Therapies Meeting.2/2017.

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62 Resection Plans for Laparoscopic Resections

63 Meet the Parents Mr. & Mrs. Robot da Vinci Si da Vinci Xi

64 Perfect Cases for the Robot

65 Is Robotics/ MIS the future of Surgery? YES Are we there today? NO Does that mean we stop trying? NO

66 RESECTABLE YES NO Surgery Can it be MADE resectable? Chemo Palliative Resection + MWA Chemotherapy and reassessment Portal Vein Embolization SIRT Staged Hepatectomy HAIP

67 What is Removed BUT What is Left Behind Key surgical question is no longer WHO IS RESECTABLE but rather WHO IS NOT RESECTABLE Future Liver Remnant of 20% (30%) Adequate Inflow and Outflow At least 2 Contiguous Segments Capability of Resecting all visible Dz RFA/ MWA to Compliment or as an Adjunct Nanoknife to Compliment or as an Adjunct ONLY absolute CONTRAINDICATION to surgery for CRLM is the presence of NON-TREATABLE DISEASE ELSEWHERE

68 The Future- is Still Multi-Modality Surgery X Research Radiology RTh X X CTh TEAM SPORT Gene Th X X Imm Th Surgeon Medical Oncologist Radiation Oncologist Gastroenterologist Radiologist Oncology Nurse Specialist Stoma Nurse Social Worker Nutritionist gsingh@coh.org Cell: (310)

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