Page 198 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 11 Interventional Oncology 177

postprocedure for bleeding. In addition, as opposed to humans, Embolization and Chemoembolization
dogs and cats require anesthesia during IA procedures. IA delivery Embolization was first described in the early 1970s when autol-
also exposes the treating clinician and patient to radiation dur-
VetBooks.ir ing the fluoroscopic procedure. Lastly, because of anesthesia and ogous blood clot was used as an embolic agent. Currently,
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embolic agents are generally categorized into permanent and tem-
equipment costs, IA procedures are more expensive than tradi-
tional drug delivery via an IV route. porary, with temporary agents such as gelatin sponge, collagen,
IA chemotherapy can be used as a sole therapy, but in humans and thrombin rarely used to treat neoplastic disease. More com-
this technique is often employed in a neoadjuvant setting as a monly, permanent embolic agents such as particles (e.g., polyvinyl
means of margin sterilization or downstaging, or in combination alcohol beads) and liquid agents (e.g., cyanoacrylate, alcohol, and
with radiation therapy as a radiation sensitizer. 19–24 Cisplatin is ethylene vinyl alcohol copolymer) are used, although there are also
well established as a radiosensitizing agent, although the exact indications for the use of other permanent agents such as coils,
mechanisms of this are still being elucidated. 22,25 Several human plugs, and balloons.
studies have demonstrated improvements in both local tumor Embolization is focused on the principle of directly target-
control rates and survival times when IA chemotherapy is com- ing the specific blood supply of the tumor with the purpose
bined with radiation therapy. 21,23,25 In a study evaluating the com- of slowing or eliminating blood flow to that tumor. Pursuing
bination of IA cisplatin with radiation therapy for the treatment of embolization often stems from the desire to achieve one of
canine bladder cancer, two dogs demonstrated an objective reduc- two goals: (1) treating a tumor primarily by diminishing the
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tion in tumor size. Side effects and toxicity were minimal in blood supply so that tumor death occurs, or (2) preoperatively
these two dogs. 26 treating a tumor to decrease blood loss during a major surgical
IA chemotherapy has been described in the treatment regi- resection. In veterinary patients, the second reason is rarely
men of canine appendicular osteosarcoma in a few studies. 27–29 used; however, further consideration for this option should be
In one study, dogs with extremity osteosarcoma were divided given, especially in tumors that are at particular risk for expe-
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into six groups: untreated, radiation alone, IA cisplatin alone, riencing blood loss such as liver, nasal, and thyroid tumors.
IV cisplatin alone, radiation therapy plus IA cisplatin, and radia- The main reason for embolization currently in companion
tion therapy plus IV cisplatin. After treatment, the tumors were animals is as a primary treatment in cases that are deemed to
resected and evaluated. In all radiation therapy groups, radiation be nonresectable or patients considered to be poor surgical
was delivered in different doses. There was a direct relationship candidates.
between the number of radiation doses (whether given with or The concept of embolization has been most evaluated in the
without cisplatin) on percent necrosis of the tumor. The radia- treatment of liver neoplasia in humans, with the publication of
tion doses predicted to result in 80% or 90% tumor necrosis hundreds of scientific articles. The liver has a unique dual blood
when radiation therapy was the sole treatment were approxi- supply, as it receives a large portion of normal blood flow from the
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mately 42 and 50 Gy, respectively. The radiation doses decreased portal vein as opposed to the hepatic artery. Interestingly, much
to approximately 28 and 36 Gy, respectively, when combined of hepatic tumoral blood supply is arterial in origin, thus allow-
with IA cisplatin. 27 ing the hepatic arterial branches and their subsequent downstream
28
In a second osteosarcoma study, IA cisplatin was admin- branches to be catheterized and treated. The outcomes associated
istered in two doses on days 1 and 21. Dogs in this study were with transarterial embolization of liver masses in humans have
randomized to receive IA cisplatin alone or IA cisplatin plus been favorable, with randomized clinical trials demonstrating a
radiation therapy. Three weeks after treatment, a limb-sparing survival benefit. 33
surgery was performed. This study demonstrated the when IA Many other organs can also be considered for targeting with
cisplatin is administered with moderate doses of radiation, a embolization despite not having a dual blood supply like the
high percent tumor necrosis was achieved. Dogs with less than liver. In humans, embolization has been described in many dif-
75% necrosis had a significantly greater local tumor recurrence ferent organs, and the literature evaluating embolization in other
rate at 1 year, of approximately 65%, compared with a 15% locations is growing. The concept for treatment in many of these
local tumor recurrence rate in dogs with greater than 75% organs is to specifically select the blood supply to the tumor while
necrosis. 28 avoiding normal blood supply to the remainder of the organ.
More recently, the early tumor response of IA chemotherapy Tumors often stimulate neovascularization, and these abnormal
was described in the treatment of lower urinary tract neoplasia in new blood vessels can be targeted by superselective catheteriza-
dogs. In this study, two treatment groups were established: (1) tion. In addition, some organs may not be needed (e.g., prostate),
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NSAID and IA carboplatin and (2) NSAID and IV carboplatin. allowing these tumors to be targeted with embolization without
Arterial access was obtained through either the carotid or femoral major concern for loss of function.
artery. Complications in the IA chemotherapy group were minor, Chemoembolization differs from embolization in that che-
and adverse events such as anemia, lethargy, and anorexia were sig- motherapy is simultaneously delivered to a tumor at the time
nificantly less likely in the group receiving IA chemotherapy com- of embolization. This provides the theoretical advantages of IA
pared with that receiving IV chemotherapy. The dogs in the IA chemotherapy, as described earlier, with the additional aspect
chemotherapy group had a significantly greater decrease in tumor that chemotherapy elimination from the target organ/tumor is
length, length percentage, width percentage, longest unidimen- altered as a result of diminished blood flow. 34,35 After emboliza-
sional measurement, and longest unidimensional measurement tion, hypoxia within tumor cells increases vessel permeability,
percentage after treatment compared with the IV chemotherapy and these factors alter cell membrane function and cause che-
group. It is important to note that this study evaluated only motherapy to be sequestered in higher concentrations within
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short-term outcome, and larger scale studies are needed to fur- tumor cells. This likely plays a major role in reduction of sys-
ther evaluate the use of IA chemotherapy for lower urinary tract temic drug exposure and a reported decrease in side effects and
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neoplasia. toxicity. 34