5. Grading System For Cirrhosis:
Child-Pugh Score
Barcelona Clinic Liver Cancer staging System
For Hepatocellular cancer
6. Llovet, J. M., Fuster, J., & Bruix, J. (2004). The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transplantation : Official
Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10(2 Suppl 1), S115–S120.
7. SURGERY
Resection
Inclusion criteria
• AJCC Stage 1-2
• Preferable size ≤5 cm, solitary tumor
• No macro vascular, L.N, or distant metastases
• Non cirrhotic or compensated cirrhotic child Pugh A
• Adequate remnant liver
• medically fit
Exclusion criteria
• Advanced stage
• Multiple tumors
• portal hypertension
• Child Pugh B & C
Transplantation
Milan Criteria for inclusion
• Single tumours ≤ 5 cm or ≤3
nodules, each≤ 3 cm
• No vascular invasion or distant
metastases
• Medically fit
In patients with multiple nodules &
chronic liver disease or chirrhosis-
transplantation preferred
8. Types of Hepatic Resections
Non anatomic resection:
wedge resection
Anatomic resection
segmentectomy
lobectomy (right and left)
trisegmentectomy (right and left)
9. Removal of a single segment - Segmentectomy
Small triangular-shaped portion of the liver along with tumor removed– Wedge
Resection.
Indicated for small superficial& peripheral lesions
10. Right lobe which consists of two segments – Right Lobectomy
Left lobe which consists of two segments – Left Lobectomy
Lobectomy: indications
• multiple lesions are located in different areas of one lobe.
11. Removal of the complete left lobe plus the medial segment of the right
lobe – Left Trisegmentectomy (also known as extended left hepatic
lobectomy)
Removal of the complete right lobe plus the medial segment of the left lobe
– Right Trisegmentectomy (also known as extended right hepatic
lobectomy
12. aim of surgery
complete resection with at least 1 cm margin
maximum preservation of normal hepatic parenchyma
Post resection liver volume:
at least 30% in non cirrhotic
At least 40-50% in cirrhotic
if potential remnant liver volume is less then following should be considered
portal vein embolization
trans arterial chemoembolization
Liver resection
13. ICG retention test
ICG is delivered systemically and the hepatic retention is measured at 15 minutes.
It determines the amount of liver resection for patients with impaired liver function
When the retention rate is less than 10%, all resections are possible.
If 10% to 20%, a bisegmentectomy is well tolerated;
if 20% to 29%, a single segment can be excised safely;
if 30% or more, the risk of liver failure with any form of resection is high.
Dynamic liver function test: to guide resection
14. Outcomes of Resection
• With improving patient selection and perioperative care, the outcome of hepatic resection has improved In
past 10 years
perioperative mortality
rate of less than 7%,
5yr overall survival rate
of 30% to 50%
15. Predictive factors determining outcome after liver resection
• TNM stage. 1
• Size
liver resection for >5 cm tumor --more recurrences.
Large HCC :propensity for vascular invasion, intraluminal & intrahepatic satellite mets
• surgical margins2,3,4
1-cm margin associated with 77% 3-year survival vs.21% with <1-cm margin.
• Type of liver resection 2,3,4
improved outcome for anatomic vs. nonanatomic resections 5-year :66% vs. 35%.
for small solitary tumors, anatomic resections less importance
1. Hasegawa K, Kokudo N, Imamura H, et al. Prognostic impact of anatomic resection for hepatocellular carcinoma. Ann Surg 2005;242:252–259
2. Shi M, Guo RP, Lin XJ, et al. Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma: a prospective randomized trial. Ann Surg2007;245:36–43
3. Ikai I, Arii S, Kojiro M, et al. Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey.Cancer 2004;101:796–802.
4. Kang CM, Choi GH, Kim DH, et al. Revisiting the role of nonanatomic resection of small (< or = 4 cm) and single hepatocellular carcinoma in patients with well-preserved liver function. J Surg
Res 2010;160:81–89
17. Liver Transplantation: results
Milan Criteria
Single tumours ≤ 5 cm or no more than 3 nodules, each≤ 3 cm
No vascular invasion or distant metastases
18. excellent outcomes of Milan criteria led to explore more expansive criteria
.
Expanded Criteria for Liver Transplantation: UCSF Criteria
Solitary lesion Within ≤ 6.5 cm
Multiple:≤ 3 nodules,each ≤ 4.5 cm
Total tumor diameter ≤ 8 cm
19. Milan criteria :5 yr survival of ≈ 70%
The UCSF criteria :5 years survival of ≈46%
Transplanted patients with tumours beyond the UCSF criteria had a survival 35%
20. Multimodality Management While Awaiting Transplant: bridge therapy
• major disadvantage with liver transplantation :long waiting time for donor organs.
• high risk of tumor progression
• To reduce tumor progression many local treatments are used such as
TACE
TART
RFA
PEI
• called as bridging therapies .
limits wait list dropout.
downstage HCC beyond transplant criteria.
decreases post transplant recurrence
21. Resection vs. Transplantation for small HCC≤ 2cm
comparable OS rates
patients with normal LFT
should be resected because
No need of immunosuppression
donor organ shortage
In patients with end-stage liver disease
transplant preferred
resection :used as bridging therapy for
transplant
25. Radiofrequency Ablation
• most widely used
• In this technique, the RF electrode placed into tumor (percutaneous or laparoscopic) with imaging
guidance.(CT,USG)
• The percutaneous approach may be limited by structures at risk such as major vessels, bile duct, diaphragm
and other intraabdominal organs
• These structures can be retracted free with a laparoscopic approach.
26. Radiofrequency Ablation
• thin probe (18 gauge) is inserted into middle of a tumor
• needle electrodes are deployed to adjustable distances.
• A.C current (400 to 500 kHz) is delivered through electrodes -agitation of particles of surrounding tissues,
• Generate frictional heat lead to sphere of necrosis.
• Size of the sphere depends on length of deployment of electrodes.
• Currently, the maximum size of probe arrays allows for 7-cm zone of necrosis, adequate for a 5-cm tumor..
27. Advantages:
Well tolerated OPD procedure
best suited to small tumors (3-5 cm) deep within hepatic parenchyma, away from hilum.
repeated easily especially percutaneous approach
Spares uninvolved hepatic parenchyma
Less invasive then resection
Disadvantges
difficulty of positioning probe
Anatomic limitation: large blood vessels may act as heat sinks, preventing adequate cytodestruction
tumors close to main portal pedicles -lead to bile duct injury
local recurrence rate (at the site of ablation) : 5% and 20%.
theoretical risk of needle tract tumor seeding:
29. RFA Vs. Liver Resection
RFA was as effective as surgical resection in the treatment of early HCC
four randomized trials comparing RFA and hepatic resection
30. no significant difference in 1-year overall survival between resection and radiofrequency ablation
long-term efficacy of surgery is better than that of RFA .
31.
32. Microwave Ablation
• Like RFA, microwave ablation (MWA) uses electromagnetic waves to produce heating.
• Unlike RFA, the MW energy is much higher frequency range 300 MHz to 300 GHz.
• Similar safety and efficacy results *
• perceived advantages of MW over RF energy include
broader deposition of MW energy
much larger zone of active heating.
less severe heat sink effects.
larger resultant ablative volume
faster treatment time
• Still not tested in clinical trials
*Wright AS, Lee FT Jr, Mahvi DM. Hepatic microwave ablation with multiple antennae results in synergistically larger zones of coagulation necrosis. Ann
Surg Oncol2003;10:275–283.
*Martin RC, Scoggins CR, McMasters KM. Safety and efficacy of microwave ablation of hepatic tumors: a prospective review of a 5-year experience. Ann
Surg Oncol2010;17:171–178.
33. Chemical Ablation
chemicals such as ethanol or acetic acid injected into tumor
destroy tumor tissue by dehydration, protein denaturation, coagulation necrosis & vascular thrombosis
advantages:
Inexpensive
Minimally invasive
Favourable at some anatomic location where RFA not suitable due to heat sink
Disadvantages:
Non selective for tumor cell & normal parenchyma
Multiple applications required
15% risk of recurrence at site of injection
RFA is superior to chemical ablation* for early stage
Tsai WL, Cheng JS, Lai KH, et al. Clinical trial: percutaneous acetic acid injection vs. percutaneous ethanol injection for small hepatocellular carcinoma—a long-term follow-up
study. Aliment Pharmacol Ther 2008;28:304–311
34. Lin, S.-M., Lin, C.-J., Lin, C.-C., Hsu, C.-W., & Chen, Y.-C. (2005). Randomised controlled trial comparing percutaneous radiofrequency thermal
ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut, 54(8),
187 patients with HCCs of 3 cm or less
randomly assigned to RFTA (n = 62), PEI (n = 62), or PAI (n = 63).
Tumour recurrence and survival rates were assessed
P valueRFAPEIPAI
NS96.1 %88.1 %92.4Complete Necrosis
RFTA v PEI, p = 0.012;
RFTA v PAI, p = 0.017
14%34%31%3yr local recurrence rate
RFTA v PEI, p = 0.031;
RFTA v PAI, p = 0.038
74%51%53%3yr survival rate
RFTA vs. PAI/PEI
p = 0.035
4.8%nonenoneMajor complications
35. Radiofrequency ablation vs. chemical ablation
RFA : more effective more complication, more expensive,
PEI/PAI: less effective more Sessions, minimally invasive, inexpensive
Lin SM, Lin CJ, Lin CC, et al. Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid
injection to treat hepatocellular carcinoma of 3 cm or less. Gut 2005;54:1151–1156
36. Embolic Therapies
Indications:
• Non surgical HCC
• intermediate stage patients
• multifocal liver-disease
• not candidates for resection, transplantation,
ablation
• no vascular invasion; no shunting; no extra
hepatic disease
Contraindications
Absolute
• Child’s C cirrhosis
• Total bilirubin > 3mg/dl
• Main PV thrombosis
Relative
• Bilirubin ≥2mg/dl
• Cardiac & renal insufficiency
• variceal bleed,thrombocytopenia
37. Arterial directed Embolic Therapies: Principal
• rely on the dual blood supply of the liver: arterial and portal venous.
• portal vein provides 75-80% of the blood to hepatic parenchyma,
• hepatic artery is primary supply of tumor.
• Selectively delivering agents trans arterially into hepatic artery targets the tumor while
sparing the liver.
• portal blood flow protect the noncancerous liver from the treatment agents and
ischemia.
38. Trans arterial embolic therapy: procedure
• interventional radiology
• performed by angiography
• gaining percutaneous access to hepatic artery
• passing catheter into branch supplying tumor.
• selective angiogram performed
• distal most branches supplying the tumor(s) identified
• embolic particles gel foam/microspheres are injected
• At completion catheter and removed & bleeding from
punctured artery controlled by applying pressure to the entry
site
40. Three types of trans arterial therapies
1. bland hepatic artery embolization (HAE)
tumor killing due to ischemia
not very effective
2. Chemoembolization (CE)
kills tumor with ischemia & chemotherapy
mitomycin C, doxorubicin, cisplatin loaded in gelatin ,pvc microspheres most commonly used
DEB: allow more distal occlusion of small vessels and delivery of high-dose chemotherapy to tumor with
low systemic circulation
3. radio embolization (RAE)/TART/internal radiotherapy
involves the administration of radioactive source loaded in glass or resin microspheres intra-arterially.
.
41. Internal radiotherapy
delivery of radioisotopes by
1. direct intra-tumour implantation via percutaneous route
2. injecting radioisotope through the hepatic artery directly into the
tumour or trans-arterial radioisotope therapy (TART).
3. parenteral injection of radiolabelled antibodies specific to HCC
antigens (radio immunotherapy)
42. TART: trans arterial radiotherapy
• Indication
inoperable HCC
Small HCC close to vital structure: ablation contraindicated
as a neoadjuvant therapy before surgery
as an adjuvant therapy, after limited surgery or ablative therapy to
reduce the risk of recurrence
HCC with portal vein thrombosis
Palliative
45. Systemic therapy
large number of clinical trials performed with chemotherapy,
given as single agent or in combination
no proven benefits on survival
Most promising results with gemcitabine1 as single agent & gemcitabine +
oxaliplatin2 or cisplatin, doxorubicin, 5-fluorouracil3 in combination.
Many other non- chemotherapeutic agents tried including LHRH agonists, tamoxifen,
IFN, statin, megestrol, vitamin K, thalidomide, interleukin-2, without any definitive
success,
1.Yang TS, Lin YC, Chen JS, et al. Phase II study of gemcitabine in patients with advanced hepatocellular carcinoma. Cancer 2000;89:750–756.
2. Leung TW, Patt YZ, Lau WY, et al. Complete pathological remission is possible with systemic combination chemotherapy for inoperable
hepatocellular carcinoma. Clin Cancer Res 1999;5:1676–1681
3. Louafi S, Boige V, Ducreux M, et al. Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma
(HCC). Cancer2007;109:1384
46. MOLECULAR THERAPY
• vascular endothelial growth factor (VEGF) promotes HCC development and
metastasis,
• Hence antiangiogenic agents studied extensively
• sorafenib is the only molecular agent approved.
• Sorafenib is a multikinase inhibitor that targets VEGF,PDGF receptor, RAF
inhibitor
47. • Phase III, multicentre RCT ,602 patients with advanced HCC Child-Pugh Class A
randomized to either sorafenib 400 mg b.d or placebo.
• primary outcomes: O.S & time to symptomatic progression.
• study was stopped, after 2nd prespecified interim analysis( 321pts.were dead)
• Median OS 10.7 vs.7.9 months in sorafinib vs. placebo (HR=0.69; 95% C.I, 0.55 to 0.87; P<0.001)
• N.S difference in median time to symptomatic progression (4.1 months vs. 4.9 months,
respectively, P=0.77).
• 7pts. in sorafenib (2%) and 2 in placebo (1%) had PR ;no patients had CR
• Diarrhea, weight loss, hand–foot skin reaction, and hypophosphatemia were more frequent
in sorafenib gp.
Llovet et al. (2008)
SHARP-Sorafenib HCC Assessment Randomized Protocol
48. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the
sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001
There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs.
4.9 months, respectively, P=0.77).
The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group
(P<0.001
50. Why RT is not the initial choice in HCC
Late presentation: large tumour-underlying chirrhosis: ONLY palliative care
HCC considered ‘radio-resistant’. Liver is relative radiosensitive; low tolerance
EBRT dose of 30 Gy@ 2Gy/# whole liver considered threshold for RILD: far less than
standard tumoradical doses. Even 25 Gy in 10 # or 32 Gy in 1.5 Gy/# bid was associated
with >5% risk of RILD, particularly with cirrhosis and chronic liver ds.
Difficult to deliver high dose
Difficult to spare liver: moves with respiration: large margin
Technology not available to deliver precise RT
51. RILD: limit dose of RT
RILD can be categorized as classic and non-classic.
Classic RILD :
• anicteric ascites, hepatomegaly, and elevated liver enzymes (particularly alkaline
phosphatase)
• typically occurs within 4 months of therapy
• veno-occlusive disease
Nonclassic RILD:
• in patients with hepatitis and cirrhosis,
• jaundice and markedly elevated serum transaminases (>5 times the upper limit of normal)
• within 3 months of completion of therapy.
• direct hepatocyte rather than endothelial injury
52. Radiotherapy For Unresectable HCC
Dose Response Relationship
higher the radiation doses
given, the higher the tumor
response seen
53. Sem Rad Onc-Dawson L 2013,21; 241-246
portal vein thrombosis
obstructive jaundice
recurrent HCC
54. Klein, J., & Dawson, L. a. (2013). HCC radiation therapy: Review of evidence and future opportunities. IJROBP87(1), 22–32.
55. Klein, J., & Dawson, L. a. (2013). Hepatocellular carcinoma radiation therapy: Review of evidence and future opportunities.
International Journal of Radiation Oncology Biology Physics, 87(1), 22–32.
SBRT has comparable
effectiveness in treating
HCC compared with
other local therapies
56. Klein, J., & Dawson, L. a. (2013).HCC therapy: Review of evidence and future opportunities. IJROBP 87(1), 22–32.
57. Klein, J., & Dawson, L. a. (2013). Hepatocellular carcinoma radiation therapy: Review of evidence and future
opportunities. International Journal of Radiation Oncology Biology Physics, 87(1), 22–32.
SBRT as bridge to transplant
RT has been delivered safely as a bridge to liver transplant, especially if other bridging therapies are
contraindicated.
58. Klein, J., & Dawson, L. a. (2013). Hepatocellular carcinoma radiation therapy: Review of evidence and future
opportunities. International Journal of Radiation Oncology Biology Physics, 87(1), 22–32.
60. Klein, J., & Dawson, L. a. (2013). Hepatocellular carcinoma radiation therapy: Review of evidence and future opportunities.
International Journal of Radiation Oncology Biology Physics, 87(1), 22–32.
61. Klein, J., & Dawson, L. a. (2013). Hepatocellular carcinoma radiation therapy:
Review of evidence and future opportunities. International Journal of Radiation Oncology Biology Physics, 87(1), 22–32.
62. Klein, J., & Dawson, L. a. (2013). Hepatocellular carcinoma radiation therapy: Review of evidence and future opportunities.
International Journal of Radiation Oncology Biology Physics, 87(1), 22–32
63. Soliman, H.,Dawson, L. a. (2012). Phase II Trial of Palliative Radiation Therapy for Symptomatic Hepatocellular Carcinoma and Liver Metastases.
International Journal of Radiation Oncology*Biology*Physics, 84(3), S10.
N=40 (21 HCC)
tumors unsuitable for resection, transplantation, RFA, systemic therapy, conformal RT, or SBRT
Eligible patients had ≥ 1 of following symptoms attributed to liver cancer: pain, abdominal
discomfort, nausea, or fatigue.
ECOG 0 to 2, expected survival > 3 months,Child Pugh A-B
8Gy SFRT
The Brief Pain Inventory (BPI), EORTC QoL completed
by patients at baseline & each follow-up
At 1 month,
48% had an improvement in symptom (primary end point)
25% had improvement of QoL (sec. end point)
65. EBRT TECHNIQUES
Simulation And Field Design
CT-based treatment planning recommended
Position: Supine with arms above head
Immobilization: wing board, alpha cradle
Contrast: oral and I.V
The CT scan taken 3- to 5-mm-thick slices from the level of the carina to L5-S1.
Treatment plans individualized
multiple fields used to precisely irradiate the tumor and spare normal tissues
66. Treatment volumes
Whole Liver (palliation only).
• AP/PA, chose borders based on CT scan
• 3DCRT reasonable because permits generation of DVHs
Partial Liver (definitive option).
• For 3DCRT/IMRT treatment planning
• GTV: defined by a arterial phase CT scan & MRI scan , fusion preferred
• CTV = GTV+ 1 cm in all directions
• PTV = CTV + 0.5 cm for setup error + margin for organ motion error
67. SBRT
Indications
One to three lesions, Maximum tumor diameter ≤ 6 cm
no extra hepatic disease.
Child-Pugh A or selective B liver disease
Comprehensive, N., & Network, C. (2015). Hepatobiliary Cancers. NCCN Clinical Practice Guidelines in Oncology, I, 1–94.
68. For SBRT treatment planning
• breathing motion should be less than 5 mm or controlled with external compression or an
ABC device.
• The CTV for SBRT should include the GTV + 0.5–1 cm.
• The PTV should include the CTV + 0.5 cm for set-up uncertainty and an additional
margin for breathing motion.
• fiducials such as gold seeds placed in the tumor by CT or US guidance can sometimes be
used to track tumor motion during respiration
• Normal tissues to be delineated include bilateral kidneys, normal and diseased liver,
spinal cord, stomach, and small bowel.
• Dose volume histograms should be used to outline dose to these structures.
69.
70. No extra hepatic, L.N vascular invasion
Non surgical HCC
intermediate stage patients
multifocal liver-disease
no vascular invasion; no shunting; no extra hepatic disease
Not suitable for lesion > 10cm
Contraindicated in shunting
Same as TACE
Portal vein thrombosis
RESECTION
RF ABLATION
TACE
Y-90 TART
SBRT
TRANSPLANT
73. Acute and Late Complications of RT
• The dose-limiting tissue injuries include the liver, stomach, duodenum,
bowels, and kidneys.
• Acute complications include general fatigue, transient elevation of
LFT, nausea, fever, and pancytopenia.
• Sub acute and late complications include hepatic failure, radiation
pneumonitis, and G.I bleeding
• Hepatic failure can be avoided by an appropriate selection of patients
and careful treatment planning.
Notes de l'éditeur
Changes in behavior with minimal change in level of consciousness+1
Gross disorientation, drowsiness, possibly asterixis, inappropriate behavior+2
Marked confusion, incoherent speech, sleeping most of the time but arousable to vocal stimuli+3
Comatose, unresponsive to pain; decorticate or decerebrate posturing+4
Harris, W. (n.d.). Hepatocellular Carcinoma : Clinical Update and Evolving Treatment Options.
The excision of surface tumors may be best accomplished as a “nonanatomic wedge” excision, in which the tumor is simply excised with a 1-cm margin.The hepatic parenchyma can be divided using a variety of techniques, with the goal to minimize blood loss and maintain adequate exposure to ensure accurate margins are obtained. This can be performed safely for tumors up to 5 cm in diameter with minimal blood loss.
Deep tumors within the hepatic parenchyma and tumors greater than 5 cm must be managed by an anatomic resection, where the most distal portal triad to the region involved by the tumor is controlled and the segment or segments are resected.
Centrally located tumors may require a lobectomy
large tumors may require an extended hepatectomy.
Lesions confined to the right lobe are amenable to en bloc removal (removal in one piece) with a right hepatectomy (liver resection) surgery.
Smaller lesions of the central or left liver lobe may sometimes be resected in anatomic “segments”.
Large lesions of the left hepatic lobe are resected by a procedure called hepatic trisegmentectomy (see diagram and explanation below).
When lesions are located peripherally (on the edges of the liver), hepatic wedge resection or anatomic segmentectomy are performed.
technetium-99m DTPA human serum albumin [99mTc-GSA] scintigraphy)
ICG binds tightly to plasma proteins and becomes confined to the vascular system.[2] ICG has a half-life of 150 to 180 seconds and is removed from circulation exclusively by the liver to bile juice.[2] fluorescent dye
It is administered intravenously and, depending on liver performance, is eliminated from the body with a half life of approx. 3–4 minutes
Theoretically, ideal therapy for HCC in cirrhotic patients because treats both the cancer & underlying parenchymal disease.
However, early experience with transplants produced dismal results.
Bismuth et al.1 was one of the first groups to consider transplant, in advanced disease,
the likelihood of systemic disease was high
recurrence rates high
long-term outcomes, were unacceptably poor.
This led to development of certain criteria of patient selection for transplantation
(Table 52.5).81–94
using these criteria for selection, patients transplanted had a very favourable outcome, including a 4-year actuarial survival rate of 85% and a recurrence-free survival rate of 92%.
The most accepted of the expanded criteria is that from the University of California San Francisco (UCSF) group.
Limited resection for intermediate stage tumor
Tumors location :accessible for percutaneous/laparoscopic/open approaches for ablation
Caution should be exercised when ablating lesions near major vessels, major bile ducts, diaphragm, and other intra-abdominal organs.
for this track can be thermally ablated while retracting the needle, which decreases this risk.
Recently, have been reported (Table 52.8).175–178 Two of them, Chen et al. and Huang et al., compared tumors fulfilling the Milan tumor criteria for transplantation. Chen et al.175 compared resection to RFA for tumors less than 5 cm in size. The 1-, 3- and 4-year survivals were 93%, 73% and 64%, respectively, for resection, and 96%, 71%, and 68%, respectively, for RFA. The authors concluded that RFA was as effective as surgical resection in the treatment of solitary HCCs ≤5 cm in terms of overall and disease-free survival after 4 years with no significant difference in outcome between the two groups on follow-up. Huang et al.177 concluded that surgical resections have better outcomes than RFAs. This conclusion was based on a recurrence rate at 5 years of 63% in the RFA group and 41% in the resection group. However, it must be pointed out that more patients in the resected group had tumors less than 3 cm in size. In addition, the overall survival was not statistically different between the two treatment groups.
for small HCC in cirrhotic, RFA has lower morbidity because it is less invasive
drug-eluting microspheres allow more reliable distal occlusion of small vessels and delivery of high-dose chemother‐ apy to the tumor with a very low systemic circulation of the chemotherapeutic agen
Drug is not washed out due to embolization
higher concentration of drug in contact with the tumor for a longer period of time
Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell.[1] In cancer therapy, an antibody with specificity for a tumor-associated antigen is used to deliver a lethal dose of radiation to the tumor cells. The ability for the antibody to specific
The ability for the antibody to specifically bind to a tumor-associated antigen increases the dose delivered to the tumor cells while decreasing the dose to normal tissues
Sealed sources are dose-limited by their effects on surrounding tissues, whereas with unsealed sources the dose of radio-isotope administered is limited by bone marrow suppression.
Iridium-192 wires are most frequently employed as a sealed intracavitary source. They may be inserted surgically, transhepatically or endoscopically. Doses of up to 60 Gy can be delivered to a malignant biliary stricture without damage to the surrounding parenchyma. The incidence of cholangitis is low if treatment is administered after insertion of an endoprosthesis.
Unsealed radio-isotope sources may be injected directly into the tumour, administered embolically via the hepatic artery in the form of microspheres or lipid droplets, or given via parenteral infusion attached to tumour-specific antibodies. Of these vehicles, the lipid agent Lipiodol appears to be the most effective and can deliver a potentially lethal dose of radiation to small tumours. Host reaction to the injected antibody remains a major drawback to the use of monoclonal antibodies as targeting agents. Iodine-131 is a beta- and gamma-emitter, producing a local tumoricidal effect and allowing accurate dosimetry by means of external scintigraphy. Yttrium-90 is a pure beta-emitter with a greater maximum beta energy and cytotoxic range; however, it is retained in bony tissues, resulting in a dose-related risk of marrow suppression. Bone absorption cannot be measured by external imaging owing to the absence of gamma emission. This lack of accurate dosimetry, coupled with the toxic side-effects of yttrium treatment, make iodine-131 the current isotope of choice
although due to their small size have much less embolic effect than a TACE procedure, with less effect on hepatic vascular dynamics[65]. Indeed, continued blood flow to treated tissue is necessary and desirable for radiation to have its intended effect through the production of free radicals. Yttrium-90 is a pure beta-emitting isotope that decays to zirconium-90 with a half-life of 64.1 h. Ninety-four percent of the total radiation dose is delivered within 11 d of the procedure. The emitted radiation penetrates surrounding liver tissue to an average depth of 2.5 mm and a maximum depth of 11 mm, such that there is essentially no expected radiation exposure to non-treated individuals in contact with the patient, and post-procedure isolation precautions are not necessary. Radiation doses delivered to the tumor, however, can be very high due to preferential flow of embolic particles toward hypervascular tumor tissue, in a ratio of between 3:1 and 20:1 compared
RAF RAPIDLY GROWING FIBROSARCOMA
The median time to symptomatic progression (which was defined as either a decrease of 4 or more points from the baseline score on the FHSI8 questionnaire or an ECOG status of 4 or death, whichever occurred first
not suitable for resection,transplantation,ablation therapies
Proximity to diapharagm,large vessel, gall bladder, GI tract
RT WITH TACE CT INTERFERON
Many retrospective and several phase 2 studies have demon- strated responses of HCC with PVT to RT. Outcomes are best in patients with preserved liver function, less extensive PVT, and lower levels of tumor markers. Guidelines