Review Article CURRENT RELEVANCE OF HEPATIC ARTERIAL THERAPY (HAT) IN THE ERA OF ROUTINE MOLECULAR TARGETED THERAPY FOR TREATMENT OF HEPATIC MALIGNANCY-A PRACTICE BASED APPROACH Puneet Gupta* , Shikha Roy ** , Om Prakash Singh*** and Harsh Rastogi**** *Senior Consultant Medical Oncology, **Resident Medical Oncology, ***Resident Medical Oncology, Senior Consultant Radiology; Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi-110076, India. Correspondence to: Dr Puneet Gupta, Senior Consultant Medical Oncology Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi-110076, India. HAT has survived it’s comparators as it has successfully evolved from hepatic artery chemotherapy(HAC), bland embolization (HAE) , chemo-embolization (HACE) to;chemo bead embolization(HACBE) , radioactive bead embolization(HARBE).The HAC is only indicated routinely in selected post hepatic metastatectomy patients with colorectal cancer whereas HACE and HARBE are routine choice for selected unresectable HCC. Key words: Hepatic arery chemotherapy, Bland embolization, Chemo-embolization, Chemo bead embolization, Radioactive bead embolization INTRODUCTION HEPATIC arterial therapy (HAT) is a drug delivery system to infuse an agent on a bolus or continuous basis directly into the hepatic arterial system; it can be selective or superselective.The rationale for HAT is that the vascular hepatic malignancy whether primary or metastatic are perfused mainly by the hepatic artery, whereas normal hepatocytes derive their blood supply from the portal vein as well as the hepatic artery. The Infusion of agents directly into the hepatic artery thus exposes the cancer to high concentrations of the agent while reducing exposure of normal liver tissue to the medications. (a) HAC form of HAT in colorectal cancer hepatic dominant disease The liver metabolizes up to 99 percent of the FUDR chemotherapy drug given by HAT, thereby reducing systemic exposure. This is how hepatic artery chemotherapy (HAC) allows a greater concentration of the agent to reach the tumor in the liver with a lower drug exposure to tissues outside of the liver and potential decrease in side effects [1,2]. HAC is an effective option because it delivers agent directly to the site of the tumor, making it appropriate as an adjuvant treatment with or without systemic chemotherapy in post expirtated or ablated colorectal hepatic metastatic disease. In unresectable hepatic metastatic disease from colorectal carcinoma (Fig. 1 & Table1) (b) HACE and HARBE form of HAT in hepatic primary cancer HCC The use of Hepatic Arterial Therapy (HAT) in hepatic primary and metastatic cancer has changed it usage in last few months due to recommendation and availability of routine molecular targeted therapy agents (MOTA) in India like Nexavar, Erbitux, Avastin etc. to be used in above situations.HAT can be executed with chemo-embolization (HACE) or radioactive bead embolization(HARBE) for unresectable hepatic metastases therapy from colorectal cancer under clinical trial setting [1]. However for unresectable, symptomatic, child pugh score A, hepatic primary carcinoma (HCC) patients the HAT is recommended in routine setting as HACE or HARBE (not as HAC) [1]. (Table 2-3 & Fig 2-3). c) HAT as HAE and HACE for Other Sites (i) From Ocular or Cutaneous Melanoma Hepatic arterial chemoembolization (HACE) for liver- dominant metastasis of melanoma is a safe treatment that results in longer survival than has occurred among historical controls. Tumor pattern on angiography was characterized as either nodular or infiltrative on the basis of angiographic appearance. Patients with lesions that have a nodular tumor appearance on angiography survive significantly longer than patients with lesions that have an infiltrative appearance on angiography [3]. Apollo Medicine, Vol. 5, No. 3, September 2008 172
Transcript
Review Article
CURRENT RELEVANCE OF HEPATIC ARTERIAL THERAPY (HAT) IN THE ERA OFROUTINE MOLECULAR TARGETED THERAPY FOR TREATMENT OF
HEPATIC MALIGNANCY-A PRACTICE BASED APPROACH
Puneet Gupta* , Shikha Roy ** , Om Prakash Singh*** and Harsh Rastogi*****Senior Consultant Medical Oncology, **Resident Medical Oncology, ***Resident Medical Oncology,Senior Consultant Radiology; Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi-110076, India.
Correspondence to: Dr Puneet Gupta, Senior Consultant Medical OncologyIndraprastha Apollo Hospitals, Sarita Vihar, New Delhi-110076, India.
HAT has survived it’s comparators as it has successfully evolved from hepatic artery chemotherapy(HAC),bland embolization (HAE) , chemo-embolization (HACE) to;chemo bead embolization(HACBE) , radioactivebead embolization(HARBE).The HAC is only indicated routinely in selected post hepatic metastatectomypatients with colorectal cancer whereas HACE and HARBE are routine choice for selected unresectable HCC.
HEPATIC arterial therapy (HAT) is a drug delivery system toinfuse an agent on a bolus or continuous basis directly intothe hepatic arterial system; it can be selective orsuperselective.The rationale for HAT is that the vascularhepatic malignancy whether primary or metastatic areperfused mainly by the hepatic artery, whereas normalhepatocytes derive their blood supply from the portal vein aswell as the hepatic artery. The Infusion of agents directly intothe hepatic artery thus exposes the cancer to highconcentrations of the agent while reducing exposure ofnormal liver tissue to the medications.
(a) HAC form of HAT in colorectal cancer hepaticdominant disease
The liver metabolizes up to 99 percent of the FUDRchemotherapy drug given by HAT, thereby reducingsystemic exposure. This is how hepatic artery chemotherapy(HAC) allows a greater concentration of the agent to reachthe tumor in the liver with a lower drug exposure to tissuesoutside of the liver and potential decrease in side effects[1,2]. HAC is an effective option because it delivers agentdirectly to the site of the tumor, making it appropriate as anadjuvant treatment with or without systemic chemotherapyin post expirtated or ablated colorectal hepatic metastaticdisease. In unresectable hepatic metastatic disease fromcolorectal carcinoma (Fig. 1 & Table1)
(b) HACE and HARBE form of HAT in hepaticprimary cancer HCC
The use of Hepatic Arterial Therapy (HAT) in hepaticprimary and metastatic cancer has changed it usage in lastfew months due to recommendation and availability ofroutine molecular targeted therapy agents (MOTA) in Indialike Nexavar, Erbitux, Avastin etc. to be used in abovesituations.HAT can be executed with chemo-embolization(HACE) or radioactive bead embolization(HARBE) forunresectable hepatic metastases therapy from colorectalcancer under clinical trial setting [1]. However forunresectable, symptomatic, child pugh score A, hepaticprimary carcinoma (HCC) patients the HAT isrecommended in routine setting as HACE or HARBE (notas HAC) [1]. (Table 2-3 & Fig 2-3).
c) HAT as HAE and HACE for Other Sites
(i) From Ocular or Cutaneous Melanoma
Hepatic arterial chemoembolization (HACE) for liver-dominant metastasis of melanoma is a safe treatment thatresults in longer survival than has occurred amonghistorical controls. Tumor pattern on angiography wascharacterized as either nodular or infiltrative on the basis ofangiographic appearance. Patients with lesions that have anodular tumor appearance on angiography survivesignificantly longer than patients with lesions that have aninfiltrative appearance on angiography [3].
Apollo Medicine, Vol. 5, No. 3, September 2008 172
Review Article
173 Apollo Medicine, Vol. 5, No. 3, September 2008
Table 1 Management of Colon Carcinoma Metastatic to Liver only
Resectable Resectable after downstaging Unresectable
Post hepatic metastatectomy hepatic Post hepatic metastatectomy Hepatic artery radioactive beadarterial FUDR + dexamethasone chemo- hepatic arterial FUDR + embolization(HARBE)-undertherapy x 6 months (HAC ) with or dexamethasone chemotherapy clinical trial setting [1]without systemic 5FU-leucovorin (HAC) with or without systemicchemotherapy if surgical and medical chemotherapy if surgical andexpertise available [1] medical expertise available [1]
Fig. 1. Super-selective right hepatic artery chemo embolization (HACE) (a) Shows intense tumor blush in this known case ofmetastatic adenocarcinoma of the right lobe of liver. The tumor had invaded the middle hepatic vein. (b) Post embolizationimage shows near complete devascularisation of the metastatic adenocarcinoma of the right lobe of liver.
(a) (b)
Table 2 Inoperable HCC: Management According to NCCN 2008 Guidelines [1]
Asymptomatic Symptomatic
Modalities of Treatment
Sorafinib(Child-Pugh score A or B) Sorafinib(Child-Pugh score A or B)
Apollo Medicine, Vol. 5, No. 3, September 2008 174
Review Article
Table 3 Radioactive bead HAT experience in hepato cellular carcinoma (hepatic primary)
Author Source Year Treatment (number of patients=n) Outcome
Kulik et al ([12] Pts with unresectable HCC(T3) underwent Y90 66% benefited in view ofJ.Surg Oncol 2006 therasphere treatment; n=35 downstaging to surgical
resection/RFA
Salem et al [13] Treatment of unresectable hepatocellular with Safe and effectiveJournal of Vascular and portal vein thrombosis carcinoma using Y-90 ;Interventional Radiology (Therasphere) n=152005
Goin et al [14] Treatment of HCC with intrahepatic Y-90 Median survivalJournal of Vascular and microsphere in Okuda low risk group n=21 731days ResponseInterventional Radiology rate 47%2005 Treatment of HCC with intrahepatic Y-90 Median survival
microsphere in Okuda high risk group n=22 374 days
Geschwind et al [15] Treatment of unresectable HCC with intrahepatic Median survivalJournnal of Surgical microsphere Y-90 in low risk group N1+n 2=121 466 daysOncology2004
Treatment of unresectable HCC with intrahepatic Median survivalmicrosphere Y-90 in high risk group N1+n2=121 108 days
Carr et al [16] Treatment of unresectable HCC in Okuda low Median survival at CLIPJournal of Liver risk group via hepatic arterial Therasphere n=54 1 2 3Transplantation 2004 812 452 216
Treatment of unresectable HCC in Okuda high risk days days daysgroup via hepatic arterial Therasphere n=26
Dancey et al [17] Treatment of unresectable HCC with intrahepatic Median survival Response rateJournal of Nuclear microsphere in Okuda low risk group n=42 649 days 38%medicine 2000 QOL Improved
Treatment of unresectable HCC with intrahepatic 302 days Over TACEmicrosphere in Okuda high risk group n=21
Treatment of unresectable HCC with intrahepatic Fewer toxicitiesmicrosphere in Okuda very high risk group n=2 than TACE
Lau et al [18] Treatment of unresectable HCC with selective Response rate 20%Journal of Int ernal Rad internal radiation using intra arterial infusion of Median survival 377 daysOncol. Biol Physics 1998 Y-90 microsphere in Okuda low risk group n=9
Treatment of unresectable HCC with selective Better survivors in low riskinternal radiation using intra arterial infusion of Can deliver higher radiation than XRTY-90 microsphere in Okuda high risk group n=11
(ii) From non-colorectal gastrointestinal tumourslike GIST, neuroendocrine tumors
HAT is effective in each of these diseases because thetumors tend to be hypervascular (like primary GIST tumors)and derive most of their blood supply from the hepaticartery. HAE is performed by instilling microscopic particlesinto a lobar hepatic artery or selectively into one of itsbranches in order to occlude the major arterial supply to thetumors. Embolization is done in stages (usually twotreatments several weeks apart) if there is bilobar disease [4-8]. No chemotherapeutic agent has been reported to haveany substantial activity against GIST when administeredsystemically.
Overall, the results of HAE compare favorably withtraditional chemotherapy in patients with disease isolated tothe liver. Nevertheless, while HAE often produces dramaticreductions in tumor burden, there is no conclusive evidencethat it prolongs survival. There are still other notableindications for HAE. It can be used to palliate patients withliver metastases who have pain refractory to medication.HAE is the treatment of choice in patients who experiencebleeding in a liver metastasis from GIST, including thosepatients who bleed on imatinib [4-8].The overall survivaltime after HAE among patients with neuroendocrine tumorsis approximately 3.5 years. The progression-free survivaltime approaches 1.5 years. The presence of extrahepaticmetastasis or an unresected primary tumor should not limit
⎫⎬⎭
⎫⎬⎭
Review Article
175 Apollo Medicine, Vol. 5, No. 3, September 2008
(a) (b)
(c)
Fig.2 A 48 year old male presented with HCC of the right lobe of the liver involving segment VIII. He underwent HACE.(a & b) Super-selective angiogram of the right hepatic artery shows numerous tumoral branches and intense tumorblush below the right dome of diaphragm. (c) Shows the tumor cast formed by the capillary bed filled with Lipiodol andthe chemotherapeutic agents after HACE.
the use of HACE or HAE [9-11].
The practice of HAT
1. Selecting the patient and tumor type(hepatic primary;hepatic metastatic)
2. Hepatic artery access
3. Selecting the HAT type ( chemo embolization, chemobead embolization, radioactive bead embolization).
4. Managing complications
(1) Patient Selection Criteria
The successful results depend on careful patientselection. Candidates for HAT should:
• have resected liver metastases from; primarycolorectal cancer (HAT under routine use)[1]
• have unresectable liver dominant metastases from;primary colorectal cancer (HAT not under routinebut trial use) [1]
• have unresectable primary liver cancer (HCC)
Apollo Medicine, Vol. 5, No. 3, September 2008 176
Review Article
(HAT under routine use) [2]
• Have resectable or unresectable liver dominantmetastases from; ocular or cutaneous melanoma;non colorectal gastrointestinal tumors like GIST,neuroendocrine [2-10]
• preferably show an absence of tumors outside theliver
• have demonstrated portal vein patency except in afew procedures of HARABE with TheraSphere.
• show no evidence of active infection.
• willing to participate in frequent pump refillappointments if required.
The procedure had fallen out of favor as not suitable todeliver chrono-modulated, long hour infusions, inconve-nience of procedure and complications like bleeding andthrombosis. However with the advent of microcatherters,availability and approval of radioactive bead (HARBE) forHepatocellular carcinoma; the technique has been revisited.The radioactive beads; chemoembolizing agents aredelivered by bolus method via femoral hepatic route. Theprocedure is done in DSA Lab at Apollo Hospital Delhi.
HAT commonly uses a small, surgically implantablepump and a catheter that carries the drug from the pump tothe hepatic artery. This allows the long term, hepatic arterialinfusion or ease of repeated spaced arterial infusionswithout need for repeated arterial access as for hepaticarterial catheter. The pump is surgically placed beneath theskin of the abdomen and its catheter is immobilized in thehepatic artery by two non-absorbable ties. The pump isfilled after the surgery with chemotherapy that is thenpumped directly into the liver through the catheter in thehepatic artery. The pump delivers a constant, prescribeddose of chemotherapy through the catheter and is refillableduring a relatively quick and painless outpatient procedure.To refill the pump, a syringe is inserted through the skin andinto the refill septum in the pump. When the syringe isdepressed, the agent (chemotherapy or radioactive bead)flows from the syringe into the pump’s drug reservoir.
(c) Hepatic Arterial Port (Percutaneous, Open)
Percutaneous implantation of an arterial (Port a Cath ) is
inserted by getting the distal left subclavian arterypunctured under the clavicle and an angiographic study ofthe hepatic district performed. Gastroduodenal artery oranomalous hepatic arteries are embolised with Gianturcocoils if required . Then a polyurethane catheter is inserteddistally into the hepatic artery and connected to the reservoirthrough a 3-4 cm subcutaneous tunnel. The port needs to beconnected to an outside arterial electronic pump.
(3) Managing Complications
The major problems with HAT of different types arevariable however in general are not surgical. They includegastritis, duodenitis, and biliary sclerosis. The mostcommon problems with HA – CT are hepatic toxicity andulceration of the stomach and duodenum. Clinically, biliarytoxicity is manifested as elevations of aspartatetransaminase, alkaline, phosphatase and bilirubin. In theearly stages of toxicity, hepatic enzyme elevations return tonormal when the drugs is discontinued and the patient isgiven a rest period. Also the bile ducts derive their bloodsupply almost exclusively from the hepatic artery and thusare too perfused with intra arterialy perfused drugs.The bileducts may develop sclerosis and stricture.Drug toxicity andmedication side effects may occur. The most commonlyreported side effects for intra-arterial FUDR are nausea andvomiting, diarrhea, and intestinal inflammation [1,2,11].
(a) There are risks associated with HAT deliveredby implantable pump such as
Complications that can occur with surgery:
• infection
• fluid build up around the implant site
• skin erosion over the site of the implant
• incision breakdown
Other possible complications include:
• Arterial thromboses.
• Catheter dislodgement.
• The catheter may erode through the wall of theduodenum when the pump has been in place formore than a year.
• Overdose or underdose of medication if certainconditions affect the rate at which the pumpdelivers medication, i.e. pump damage due tostrenuous activity, high heat or cold exposure , or achange in air pressure , direct damage by impact tothe body in the area of the pump as in contactsports.
Review Article
177 Apollo Medicine, Vol. 5, No. 3, September 2008
• Disruption in therapy if the pump is damaged byimproper handling or filling.
• Drug delivered to organs other than the liver. Adisruption in therapy if the pump or catheter isdamaged by improper handling or filling; drugs oruses not intended for the pump; plugging or tearingthe catheter; or manipulating the pump or catheterthrough the skin (manipulation can result inmoving the catheter or pump from its intended site)[19-20].
Embolization is usually done in two treatments severalweeks apart if there is bilobar disease. Many patientsexperience a post-embolization syndrome that includesabdominal pain, fever, nausea, and ileus. Hepatic enzymesare often elevated transiently. Rarely, cholecystitis orpancreatitis occurs due to inadvertent embolization of thecystic or gastroduodenal arteries. The most fearedcomplications of HAE are liver abscess and liver necrosis,which are rare [20,21].
To facilitate the practice of HAT the following sampleforms are furnished.
(b) Precautions to avoid complications
• Strict aseptic techniques should be used to preventinfection during all procedures.
• Pump flow rate will vary depending on factorssuch as body temperature, altitude, arterial
pressure at the catheter tip, and solution viscosity.
• Patients should not attempt to resterilize the pump.
• The manufacturer’s instructions should befollowed regarding drug preparation, dosage, andadministration.
• FUDR should be used with added caution inpatients with impaired liver or kidney function.
(c) Complications
HAC has unique toxicities, including chemicalhepatitis and biliary sclerosis, which can be mitigated by theaddition of dexamethasone to therapy. During the course oftreatment, pump pocket infections occur rarely. At the firstsign of infection at the pump pocket, systemic antibioticsneed to be started. The pump needs to be moved to a newlocation in a newly created pocket if the infection does notresolve itself. The old pocket should be opened and drained[11,19-21].
CONCLUSION
In Hepatocellular carcinoma (HCC) the HAT is aroutine option in advance unresectable or surgery non-willing patient only if disease is symptomatic and patient iswith child Pugh score A; otherwise in asymptomaticadvance child Pugh A HCC the MOTA using sorafinib, Amulti kinase inhibitor (oral Tab. Nexavar) is the treatment ofchoice [2]. The HAT is recommended currently in MOTAera for unresectable hepatic colorectal metastatic
(a) (b)
Fig. 3. This 43 year old male is a known case of hepatocellular carcinoma of the left lobe of liver. The tumor had invaded theportal vein. His liver function tests were mildly deranged. He underwent HARBE. (a & b) show fibered coil disconnectingthe gastroduodenal artery from the hepatic vasculature, super-selective left hepatic artery angiogram shows the tumorblush prior to administration of Yttrium-90 beads into the left lobe.
Apollo Medicine, Vol. 5, No. 3, September 2008 178
Review Article
Patient Assessment for HATName : ……………………………………………………………………………….....................................………...
Age/Sex : ……………………………...….I. D. No……………………………………………..................................….
( inj Rantac……….. , inj Granisetron………… ,inj Decadron…………. ) od for 2 days
Steroids
Inj Methyl Prednisolone……………. for ……….days.
Tab Prednisolone …………………….mg daily by mouth and till one day after HAT
Inj. Efcorlin ………………………….for …………days
Analgesics
Inj Tramazac……………..
Inj ……………..
Octreotide for Somatostatin receptor scintigraphy positive tumors
inj Octreotide 24hrs before HAT (SC 100mcg tds for 10 days)………………………
Chemoprotector for CISPLATIN based HAT.
Inj. Sodium thiosulphate 9 gm / sq m immediately before chemotherapy as IV bolus
Glucagon
Inj glucagons (0.1mg/hr IV infusion)………………..to be given just before HAT and for 48 hrs
disease(HCRMD) under clinical trial setting and routinelyfor adjuvant use after hepatic colorectal metastatectomy [1].The HAT is also useful in non-colorectal hepatic dominantmetastatic vascular disease from ocular or cutaneousmelanoma; gastrointestinal stromal tumor (GIST) andneuroendocrine cancer [3-10].
REFRENCES
1. National comprehensive cancer network; clinical practice
guidelines in oncology, colon cancer V.2.2008;www.nccn.org.
2. National comprehensive cancer network; clinical practiceguidelines in oncology, hepatobiliary cancers, V.2.2008;www.nccn.org.
3. Karun V. Sharma, Jennifer E. Gould, J. William Harbour,Gerald P. Linette, Thomas K. Pilgram, Pouya N. Dayani,Daniel B. Brown Hepatic Arterial Chemoembolization forManagement of Metastatic Melanoma AJR 2008; 190: 99-104.
Apollo Medicine, Vol. 5, No. 3, September 2008 180
Coil embolization to protect stomach and duodenum potential reflux
Yettrium - 90 microspheres
Iodine - 131 Lipoidol to prepare chemo emulsion
Polyvinyl particles (300, 500, 700/um) for permanent arterial occlusion
Degradable Starch Micro Spheres
Gelatin foam particles for temporary occlusion
Gelatin powder
Catheters
Regular pulses in between chemotherapy
Single lobe embolization
Major hepatic artery branch chemoembolization
Adriamycin … mg/sqm/day one dose of mg over once/ daily for total dose
5FU … mg /sqm/dose one dose of mg over once/ daily for total dose
Mitomycin … mg /sqm/dose one dose of mg over once/ daily for total dose
FUDR … mg /kg/dose one dose of mg over once/ daily for total dose
Inj Decadron … mg /kg/dose; one dose of mg over once/ daily for total dose
Cisplatin … mg /sqm/dose; one dose of mg over once/ daily for totaldose
Mannitol … mg /kg/dose; one dose of mg over once/ daily for total dose
Leucovorin … mg /sqm/dose; one dose of mg over once/ daily for totaldose
Carboplatin … mg /sqm/dose; one dose of mg over once/ daily for totaldose
Water - based contrast to reconstitute chemo.
4. Mavligit GM, Zukwiski AA, Ellis LM, Chuang VP,Wallace S. Gastrointestinal leiomyosarcomametastatic to the liver. Durable tumor regression byhepatic chemoembolization infusion withcisplatin and vinblastine. Cancer 1995; 75:2083-2088.
5. Rajan DK, Soulen MC, Clark TW, Baum RA, Haskal ZJ,Shlansky-Goldberg RD, et al. Sarcomas metastatic to theliver: response and survival after cisplatin, doxorubicin,mitomycin-C, Ethiodol, and polyvinyl alcoholchemoembolization. J Vasc Interv Radiol 2001; 12: 187-193.
Review Article
181 Apollo Medicine, Vol. 5, No. 3, September 2008
HAT Type………...…………………………………………...........................................................…………………..…………..
Antiemetics
………………………. …one dose of mg over once/ daily for total dose
………………………. …one dose of mg over once/ daily for total dose
………………………. …one dose of mg over once/ daily for total dose
Analgesic
………………………. …one dose of mg over once/ daily for total dose
………………………. …one dose of mg over once/ daily for total dose
Inj Morphine sulfate …one dose of mg over once/ daily for total dose
Antimicrobials
………………………. …one dose of mg over once/ daily for total dose
………………………. …one dose of mg over once/ daily for total dose
Syrup Benadryl one dose of mg over once/ daily for total dose
Chemoprotector for CISPLATIN -
Inj Sodium thiosulfate immediately after HAT @ 1.5 mg/sqm/hr as a 6 hr infusion
one dose of mg over once/ daily for total dose
Complications related to HAT
Pain in liver region Event with date
Tiredness , Loss of appetite
Fever , Nausea ;Vomitting , Malaise
Leukemoid reaction (Increased white cell blood count)
Increase in serum bilirubin because of hepatic necrosis
Bacteremia,Pneumonia , Arterial desaturation
Ascites ,Pleural effusion
Encephalopathy , Kidney dysfunction
Intrahepatic abscess , Gall bladder ischemia
Stomach ulcer , Duodenum ulcer
Hypothyroidism because of retained iodine load
Post - HAT evaluation
To repeat chemotherapy after 4/8/12 weeks after assessment by
Non contrast CT scan after………………………………………
Triple phase contrast CT scan after…………………………….
MRI with contrast without contrast after……………………………
PET… after…………………………………………………………………
To consider for surgery…on ……………………………………..
To repeat HAT ……………………………………
To consider RFA on…………….. Unfit for RFA because of heat flush.
Apollo Medicine, Vol. 5, No. 3, September 2008 182
Review Article
6. Calvo DB, III, Patt YZ, Wallace S, Chuang VP, BenjaminRS, Pritchard JD, et al. Phase I-II trial of percutaneousintra-arterial cis-diamminedichloro platinum (II) forregionally confined malignancy. Cancer 1980; 45: 1278-1283.
7. DeMatteo RP, Shah A, Fong Y, Jarnagin WR, Blumgart LH,Brennan MF. Results of hepatic resection for sarcomametastatic to liver. Ann Surg 2001; 234: 540-547.
9. Gupta S, Johnson MM, Murthy R, Ahrar K, Wallace MJ,Madoff DC, McRae SE, Hicks ME, Rao S, Vauthey JN,Ajani JA, Yao JC. Hepatic arterial embolization andchemoembolization for the treatment of patients withmetastatic neuroendocrine tumors: variables affectingresponse rates and survival. Cancer. 2005;104(8):1590-1602.
10. Ho AS, Picus J, Darcy MD, Tan B, Gould JE, Pilgram TK,Brown DB.Long-term outcome after chemoembolizationand embolization of hepatic metastatic lesions fromneuroendocrine tumors. AJR 2007; 188(5):1201-1207.
11. Cancer: Principles and Practice of Oncology: LippincottWilliams & Wilkins Author(s): Vincent T. DeVita, Jr.,Samuel Hellman; and Steven A. Rosenberg, 7th ed. 2005
12. Kulik LM, Atassi B, Holsbeeck LV, Souman T, LewandowskiRJ, Mulchay MF, et al. Yttrium-90 Microspheres(TheraSphere®) Treatment of UnresectableHepatocellular Carcinoma: Downstaging to Resection,
RFA and Bridge to Transplantation. J Surg Oncol. 2006;94: 572-586.
13. Goin, Salem, Carr, et al. Journal of Vascular andInterventional Radiology 2005; 16: 195-203.
14. Salem, Thurston, Carr, et al. Journal of Vascular andInterventinal Radiology 2005; 13(9): S223-S229.
15. Geschwind ,Garren, N.Joseph, et al. Journal of SurgicalOncology 2004;14(4):179-193.
16. Carr R. Salem, R. Hunter, et al. International Journal ofRadiation Oncology Biology Physics 2004, 66 (2): S83-S88.
17. Dancey Dancey JE, Shepherd FA, Paul K, et al. Treatmentof nonresectable hepatocellular carcinoma withintrahepatic 90Y-microspheres. J Nucl Med 2000; 41:1673-1681.
18. Lau WY, Ho S, Leung TW, et al. Selective internal radiationtherapy for nonresectable hepatocellular carcinoma withintraarterial infusion of 90yttrium microspheres. Int JRadiat Oncol Biol Phys1998; 40(3): 583-592.
20. Link, Karl H, Marko Kornmann, et al. ThymidylateSynthase Quantitation and In Vitro ChemosensitivityTesting Predicts Responses and Survival of Patients withIsolated Nonresectable Liver Tumors Receiving HepaticArterial Infusion Chemotherapy. Cancer 89, no 12 (July 15,2000): 288-289.
21. Venook, Alan, Betsy Althaus, et al. Hepatic Arterial Infusionof Chemotherapy for Metastatic Colorectal Cancer. NewEngland Journal of Medicine 2000; 342, (20) : 1524.
