Treatment of liver tumours current trends
Download as PPTX, PDF9 likes1,148 views
This document discusses current trends in the treatment of liver tumors. It covers various types of liver tumors including primary and secondary tumors. For hepatocellular carcinoma (HCC), the main treatment options discussed are surgical resection, liver transplantation, radiofrequency ablation, transarterial chemoembolization (TACE), radiotherapy, and targeted therapy. For colorectal liver metastases, surgical resection is the main treatment discussed along with ablation, liver directed therapies like TACE, and chemotherapy. The document provides details on patient selection criteria, techniques like portal vein embolization to improve outcomes of resection, and prognostic scoring systems for colorectal liver metastases.
Treatment of liver tumours current trends
- 1. Treatment of Liver Tumours- Current Trends Dr.Venugopal B Dept .of HPB & Liver Transplant KIMS, Thiruvananthapuram.
- 2. Liver Tumours • Benign • Malignant -Primary Hepatocellular ca Cholangio Ca -Secondary Colorectal Neuroendocrine Non colorectal non neuroendocrine
- 3. Hepatocellular carcinoma • 5th most common malignancy • 3rd most common cause of cancer death • 70% occur in Cirrhotic livers • Incidence is increasing
- 4. Treatment options • Surgical resection • Liver transplantation • Radiofrequency ablation • TACE, TARE • Radiotherapy • Targeted therapy
- 5. Treatment selection • Applicability • Safety • Efficacy
- 6. BCLC staging
- 7. Surgical resection • Cirrhotics with HCC (<5%) • HCC without cirrhosis • Criteria -Child-Pugh class A -Normal bilirubin -Absence of portal hypertension - <5cm in diameter
- 8. Postoperative Liver Failure is the commonest cause of mortality
- 9. Risk factors for Liver Resection • Advanced age • Comorbidities • Chronic Liver Disease • Cholestatic liver • Post chemotherapy liver • Extent and complexity of the resection
- 10. Cause of Postoperative Liver Failure • Impaired functional reserve • Inadequate residual volume
- 11. Risk assessment • Clinical • Biochemical • Volumetric • Functional
- 12. Portal hypertension • Previous variceal haemorrhage or ascites • Presence of oesophageal varices • Platelet count <100000 • Radiologically visible portosystemic shunt
- 13. Indocyanine green clearance test < 14% 14-20% >20% Major hepatic resection contraindicated & Adequate liver remnant CT Major hepatectomy
- 14. Child- Pugh score • Child A - major liver resection • Child B - segmental/subsegmental resection • Child C - Absolute contraindication
- 15. Contrast CT scan • Site , Size • Relation to blood vessels • Residual liver volume(FLRV)
- 16. TUMOR VOLUME
- 18. Safe remnant liver volume Residual liver volume • FLRV = Total liver volume - Tumor volume • >30% - Normal liver • > 40% - Cirrhotic
- 21. Strategies to deal with impaired functional reserve • Parenchyma sparing resection • Resection after PVE • Resection in combination with RFA • Two stage resection • Resection after chemotherapy • Resection after TACE
- 22. Augmentation FLRV • PVE • PV ligation • Repeat CT after 3 weeks • FLRV increases by 20-46% • Resectability 70 to 100 % • Can be used as a dynamic test for liver regeneration
- 23. not randomized but alternatively assigned 28 pts with PVE 27 pts without PVE Portal Vein Embolization Before Right Hepatectomy Farges O, Belghiti J et al, Ann Surg 2003;237:208-17 future liver remnant volume after PVE 4419% in normal liver 3528% in chronic liver disease the postoperative course and complications similar between PVE(+) and (-) in normal liver significantly decreased in PVE(+) with chronic liver diseases, but no difference in surgical mortality
- 31. Surgical resection -Result • 5 yr survival: 60-70% • Tumour recurrence: 50% at 3 yrs
- 32. Liver transplantation for HCC • Ideal treatment for small HCC in Cirrhotics -Widest possible surgical margin! -Cure of underlying liver disease (denovo tumorogenesis)
- 33. Early Results Survival(%) Recurrence (%) Center 1 yr 2 yr 3 yr Cincinnati 45 30 20 39 UCLA 40 22 – 67 Cambridge 45 38 – 65 Pittsburgh 64 47 48 43 Liver Transplantation for Hepatocellular Carcinoma
- 34. Liver Transplantation for HCC • Early experience in 1980s- disappointing • Paul Brousse > 50% DFS 3yrs Single <3cm, < 3tumour Bismuth etal. Ann Surg 1993 • Milan group 4yr OS 75% DFS 83% Single <5cm, <3 tumours <3cm Mazaffero etal. NEJM 1996
- 35. UCSF Criteria • Lesion <6.5cm • 2-3 lesions -Largest <4.5cm -total dia <8cm • No vascular invasion • No extrahepatic metastases • One yr survival 90% • Five yr survival 75% Yao FY etal.Hepatology2001;33: 1394-403
- 38. Radiofrequency Ablation • Local application of thermal energy generated by high frequency electric current • Complete ablation in tumours up to 4cm
- 40. • 148 pts, single, small (< 4cm) • RFA: 55 pts, Resection: 93 pts • Recurrence: RFA: 58.2%---- 40% remote, 18.2% local Resection: 45.2%---- 43% remote, 2.2% local • Survival: RFA: 100%, 72.7% at 1 & 3 yrs Resection: 97.9%, 83.9% at 1 & 3 yrs SN Hong et al. J Clin Gastroenterol 2005;39:247 Samsung Medical Center, Seoul, Korea Hepatocellular Carcinoma Resection vs RFA
- 41. BEFORE RF AFTER RF
- 42. Resection vs RF ablation • Similar results for tumours < 3cm • Comparable for 3 to 5 cm • Resection better for >5cm
- 43. Transarterial chemoembolisation- Contrindications • Serum bilirubin >2mg/dl • LDH >425 U/L • AST >100 U/L • Tumour burden >50% of the Liver • Cardiac or renal insufficiency • Ascites,recent variceal bleed or significant thrombocytopenia
- 44. Transarterial Chemoembolization Meta-analysis of 7 randomized controlled trials • 2 yr survival: 41% (19-63%) • Treatment response: 35% (16-61%) • Average no. of sessions: 1-4.5 • Risks: – Infection – Tumor lysis syndrome – Hepatic failure • Llovel J He aloI2003"37:429
- 45. Radioembolization • Similar to TACE • Use radiation particles eg Yttrium, Rhenium • Results slightly better than TACE
- 46. Targeted therapy • Sorafenib -increases survival -Disease progression delayed
- 48. Introduction Liver is the most common site for hematogenous metastasis from colorectal carcinomas. ~ 25% synchronous. Bengmark S. Cancer 23: 198- 202 ~ 50% metachronous Bozzetti F. Ann Surg 205:264- 270 In patients with isolated liver metastasis, the extent of liver disease is the prime determinant of survival.
- 49. Natural History of CRM Stangl R et al –Lancet 1994 Prospective study 1980-1990 484 consecutive untreated patients Avg survival(yr) 31%-1 ,7.9%-2, 2.6%-3, 0.9%-4 (Median survival 7.5 months) The prosnosis is most closely related to the extent of liver replacement by tumor.
- 50. Natural History of CRM • Wagner JS Ann Surg 1984 Study comparing outcome in potentially operable but not resected metastases with those who underwent surgery 5- year survival 25% in the operated group compared to 2%in the nonoperated group.
- 51. Colorectal liver met-treatment options • Resection • Ablation • Liver directed therapy • Chemotherapy
- 52. Rationale for treatment • Spread to liver is via portal circulation before systemic spread. • Stepwise spread provides an opportunity to prevent dissemination of tumor to other sites by treatment of hepatic metastasis. • This way hepatic colorectal metastasis differ from other metastasis. • Regenerative capacity of liver has allowed major resections to be possible with increasing frequency
- 53. • Hepatic resection has become standard treatment after Foster et al showed survival after hepatic resection to be consistently above 20% as compared to 0% with no treatment. • With improvement in surgery, resection of hepatic metastatic tumors have been increasingly undertaken • 5 year survival after margin negative hepatic resection have been 24-58%(40%) with 10 year survival of 15-20%.
- 54. Prognostic scoring • Fong et al Ann Surg 1999 Data base of 1001 consecutive patients undergoing hepatic resection for CR metstases 5 preoperative clinical criteria for clinical risk score • Disease free survival <12 months • Number of mets >1 • Preoperative CEA level>200U/ml • Size of largest lesion >5cm • Lymphnode positive primary tumor
- 55. Clinical risk score • Presence of any one characteristic was associated with 5 year survival of 24-34% • Score of 2 or less –good prognosis (ideal for resection) • 3-4 outcome less favorable so aggressive trial of adjuvant therapy required • 5- long term survivors are rare so adjuvant treatment trials are required
- 56. Patient selection -Imaging • CECT • MRI • PET Scan
- 57. Effect of PET Before Liver Resection on Surgical Management for Colorectal Adenocarcinoma Metastases A Randomized Clinical Trial Carol-Anne Moulton, MB, BS; Chu-Shu Gu, MSc; Calvin H. Law, MD; Ved R. Tandan, MD; Richard Hart, MD; Douglas Quan, MD; Robert J. Fairfull Smith, MB; DiederickW. Jalink, MD; Mohamed Husien, MD; Pablo E. Serrano, MD; Aaron L. Hendler, MD; Masoom A. Haider, MD; Leyo Ruo, MD; Karen Y. Gulenchyn, MD; Terri Finch, BA; Jim A. Julian, MMath; Mark N. Levine, MD; Steven Gallinger,MD CONCLUSIONS AND RELEVANCE Among patients with potentially resectable hepatic metastases of colorectal adenocarcinoma, the use of PET-CT compared with CT alone did not result in frequent change in surgical management. These findings raise questions about the value of PET-CT scans in this setting. JAMA. 2014;311(18):1863-1869. doi:10.1001/jama.2014.3740
- 58. Patient selection –Criteria for unresectability • Nontreatable extrahepatic disease • Unfitness for surgery • Involvement of >70 % of liver or 6 segments
- 59. Resectability • Currently, hepatic colorectal metastases should be defined as resectable when – Disease can be completely resected – 2 adjacent liver segments can be spared – Adequate vascular inflow and outflow and biliary drainage can be preserved – Volume of the liver remaining after resection (i.e., the ‘‘future liver remnant’’) will be adequate (at least 20% of the total estimated liver volume). • Instead of resectability being defined by what is removed, decisions regarding resectability should now focus on what will remain following resection.
- 60. Who cannot be operated
- 61. Resection for CRLM- Clinical situation • Synchronous lesions • Metachronous lesions
- 62. Timing of resection and synchronous lesion • Best timing not yet defined • Most investigators recommend staged approach 2-3 months after resection of primary • Recently few series have shown equal results with simultaneous resections
- 63. • Staged or simultaneous resections can be considered depending on – Complexity of resections – Symptoms – Comorbid disease – Available surgical expertise
- 64. Extrahepatic disease • No longer be considered an absolute C/I to hepatic resection – If the patient is carefully selected – Complete (margin-negative) resection of both intra- and extrahepatic disease is feasible. • Survival rate was significantly higher in patients with – fewer than five liver metastases – Who received neoadjuvant chemotherapy – In whom a complete resection could be achieved.
- 65. Residual liver volume • 20% of residual liver volume is adequate for normal liver • Most paitents with CRM have received chemotherapy and have CASH • Exact extent of FRLV has not been defined. • PVE helps in improving the resectability by hypertrophy of residual liver and providing adequate FRLV.
- 66. Indications of PVE • FLRV ≤ 20% of TLV in patients with normal liver • FLRV ≤ 30% of TLV in patients who have received extensive chemotherapy; • FLRV ≤ 40% of TLV in patients with hepatic fibrosis or cirrhosis.
- 67. Margin status • Negative resection margin decreases local recurrence rates and improves survival • Cady et al recommended minimum margin of 1 cm • Multicenter study 0f 557 pts. • No difference in 5 yr OS or tumour recurrence rate for tumour free margin of 1-4mm,5-9mm or >10mm Ann Surg 2005: 241:715
- 68. Radiological vs Pathological response • Radiological complete response is rarely associated with complete pathological response • Pathological response only in 4 to 9 % • Mapping and timing of resection are critical. • Resection should encompass segments involved based on pre-chemotherapy imaging.
- 69. Metachronous mets- Timing of sugery Upfront Surgery vs Upfront Chemotherapy
- 70. Upfront surgery indications • Low risk patients -medically fit -four or fewer lesions • Potentially resectable
- 72. EORTC 40983- Perioperative FOLFOX vs. Surgery for resectable CRLM • Eligibility: • 1-4 Liver metastases that were technically resectable • No extrahepatic (non-primary) disease • No prior oxaliplatin • Design: • Experimental arm: 6 cycles (12 weeks) FOLFOX4 pre- and post surgery Lancet. 2008 Mar 22;371(9617):1007-16
- 73. EORTC Trial • Total no 364 Chemo 182 Resection 182 Resection rate 83% vs 84% Nontherapeutic Lap 8/159(5%) vs 18/170(11%) Postop complications 25% vs 16 % Mortality 1 vs 2
- 74. EORTC Result • Media follow-up 8.5 yrs • 5 yr PFS 38% vs 30%( HR 0.81, p= 0.068) • 5 yr OS 51% vs 48% (HR 0.88, 95% CI 0.68- 1.14)
- 75. Aggressive surgical approach • Repeat hepatectomy: 60-70% of operated cases develop recurrance. One third are liver only mets. • Of these 10- 15% candidates for repeat resection. • Periop mortality 1- 9% • Median survival 37 months. Jarnagin. Ann Surg • Recurrence rate ~70%
- 76. Aggressive surgical approach • En bloc vascular (IVC, hepatic vein) resection and Ex vivo surgery: • For liver mets in central and posterior segments. • Significant mortality and morbidity (~30%) • Median survival 19 months. Miyazaki M. Am j Surg
- 78. Conversion chemotherapy • Preoperative chemotherapy permits complete resection in 12-33% of patients who were considered unresectable • Survival in these patients is similar to those who have hepatic resection upfront ( 5yr SR 30 to 35%) • Chemotherapy regimens based on (5-FU) rarely provided sufficient intrahepatic tumoricidal effect to convert hepatic metastases from unresectable to resectable (response rate < 20%). • Actual conversion only 5 to 15%
- 79. Study Phase Regimen Number of patients Response rate Resection rate R0 rate First BEAT IV Chemotherapy+ bevacizumab 1914 704 (liver only) 225 (11.8%) 107 (15.2%) 173 (9.0%) 85 (12.1%) NO16966 III FOLFOX/XELOX+ bevacizumab FOLFOX/XELOX+ placebo 699 211 (liver only) 701 207 (liver only) 38% 38% 44 (6.3%) 24 (11.6%) 34 (4.9%) 24 (11.6%) CRYSTAL III FOLFIRI+cetuxi mab FOLFIRI 599 599 57.3% (WT) 39.7% (WT) 7% 3.7% 4.8% 1.7% OPUS II FOLFOX+cetuxi mab FOLFOX 169 168 57% (WT) 34% (WT) 4.7% 2.4% CELIM II FOLFOX+cetuxi mab FOLFIRI+cetuxi mab 56 55 68% 57% 20 (38%) 16 (30%) Table 2. Conversion rates in unresectable colorectal cancer liver metastases patients treated with bevacizumab or cetuximab containing regimens. WT, KRAS wild-type.
- 80. Intra arterial approaches • Infusion • Chemoembolization • Radioembolization (SIRT)
- 81. • Given the effectiveness of systemic chemotherapy, regional chemotherapy should be used in conjunction with systemic chemotherapy. • Too little data exist to determine an overall advantage of one form of regional therapy over another
- 82. RFA • RFA is indicated in unresectable tumors due to – Size – Location – Number of lesions – Co morbid conditions • Mainly used as palliative therapy • Can be used with resection in borderline resectable tumors
- 84. Metastatic Liver Tumors – Neuroendocrine Tumors • Functional (carcinoid syndrome) • Non functional
- 85. Metastatic Liver Tumors – Neuroendocrine Tumors Workup • CT • MRI • Octeriotide scan • Dota PET scan
- 86. Metastatic Liver Tumors – Neuroendocrine Tumors Treatment modalities • Liver resection and debulking (90% debulking) • Ablation • Liver directed therapy; chemoembolization, radioembolization • Chemotherapy or hormonal therapy • PRRT
- 87. Metastatic Liver Tumors – Neuroendocrine Tumors Hepatic resection surgical resection is the first line treatment Rationale Slow growing tumor (ineffective to radiochemotherapy) Biologically active tumors – mass dependent hormone production 5 yr survival- 85- 100%
- 90. Metastatic Liver Tumors – Neuroendocrine Tumors Hepatic Transplantation • Offers potential for cure or best palliation •Prerequisites – complete excision of primary & regional disease • 5 yr survival- 36- 89%
- 91. Metastatic Liver Tumors – Neuroendocrine Tumors Hepatic Transplantation •Factors increasing survival (Fernandez 2003) – Age less than 50 years –Limited hepatic metastases – low Ki67 index – regular E-cadherin staining – R0 resection of the primary NET with no
- 92. Non colorectal Non neuroendocrine Metastasis (NCNN) • Role of hepatectomy in (NCNN) tumors not well defined • Increasing publications • Overall 5 yr survival: 25- 36% • Tumors of various pathological types resected – Influences the outcome
- 93. Non colorectal Non neuroendocrine Metastasis (NCNN) MSKCC series from 1981- 2002 Tumor pathology %age Breast 20 Melanoma 12 Reproductive tract 28 Testicular 14 Gynecologic (ovarian, endometrial, cervical) 14 Adrenocortical 11 Renal 8 Gastrointestinal ( stomach, duodenum, periampullary, anal) 9 Others (lung, salivary gland, nasophyrangeal, thyroid, tonsil, sweat gland) 9 Unknown 3
- 94. Non colorectal Non neuroendocrine Metastasis (NCNN) MSKCC series from 1981- 2002 Tumor pathology %age Breast 20 Melanoma 12 Reproductive tract 28 Testicular 14 Gynecologic (ovarian, endometrial, cervical) 14 Adrenocortical 11 Renal 8 Gastrointestinal ( stomach, duodenum, periampullary, anal) 9 Others (lung, salivary gland, nasophyrangeal, thyroid, tonsil, sweat gland) 9 Unknown 3 Median follow-up: 35 months 30 day mortality- 0 % 3-year relapse-free survival rate was 30% 3-year cancer-specific survival rate was 57%
- 95. Liver Metastases: Gastric GIST with liver mets • Most common indication among sarcomas • Imatinib changed natural history of the disease • 5-year overall survival rate: 30% in resected patients versus only 4% who do not underwent resection MSKCC data
- 98. Thank you