DOI:10.2214/AJR.05.1106
AJR 2006; 187:746-750
© American Roentgen Ray Society
Percutaneous Radiofrequency Ablation of Ovarian Cancer Metastasis to the Liver: Indications, Outcomes, and Role in Patient Management
Debra A. Gervais1,
Ronald S. Arellano1 and
Peter R. Mueller1
1 All authors: Department of Radiology, Massachusetts General Hospital, 55 Fruit
St., White 270, Boston, MA 02114.
Received June 28, 2005;
accepted after revision August 12, 2005.
Address correspondence to D. A. Gervais.
Abstract
OBJECTIVE. Stages III and IV ovarian cancer are treated with a
combination of chemotherapy and resection, in some cases including second and
third surgical procedures, to achieve cytoreduction. Percutaneous
radiofrequency ablation has proved effective in local control of hepatic
tumors. We report early experience with percutaneous radiofrequency ablation
in the management of isolated foci of metastatic ovarian cancer and assess the
efficacy of the technique in achieving and maintaining local control by
percutaneous cytoreduction.
CONCLUSION. Percutaneous radiofrequency ablation is effective in
achieving local control in selected patients with metastasis from ovarian
cancer. In patients with limited macroscopic disease, cytoreduction can be
achieved without surgery.
Keywords: oncology • ovarian neoplasm • percutaneous ablation • radiofrequency ablation
Introduction
Standard management of advanced (stages III and IV) ovarian cancer involves
surgical resection and chemotherapy. Cytoreduction has been shown to have
survival benefit in some studies. The results of these studies support the
practice of repeated surgery to remove recurrent or new disease in the
abdomen, pelvis, and retroperitoneum
[1-4].
Since the mid 1990s, radiofrequency ablation of selected primary and secondary
hepatic tumors has had promising results in local control of these tumors
[5]. Because of the potential
benefits of cytoreductive surgery, radiofrequency ablation in selected
patients with ovarian cancer may achieve similar cytoreduction without
repeated open surgical resection
[6-9].
We report our experience with a series of consecutively treated patients with
ovarian cancer involving the liver who underwent percutaneous radiofrequency
ablation with the goal of local control of the target tumor. Ovarian cancer
involving the liver can signify stage III (surface lesions) or stage IV
(parenchymal lesions) disease.
Materials and Methods
Patient Demographics and Medical Record Review
Over a 6-year period, six women (age range, 44-80 years; mean age, 61
years) with six tumors (1.5-5.3 cm; mean diameter, 2.7 cm) underwent
percutaneous radiofrequency ablation for ovarian cancer metastatis to the
liver. Retrospective review of medical records and imaging findings was
performed with permission from the institutional human studies review
committee. Imaging studies were reviewed for tumor site, tumor size, size of
zone of ablation, evolution of the zone of ablation, and development of local
recurrence or new distant disease. Medical records were reviewed for
histopathologic features of the tumor, tumor markers, patient outcome,
development of distant disease, therapy before and after radiofrequency
ablation, results of radiofrequency ablation, and complications of
radiofrequency ablation.
Radiofrequency Ablation
All patients were referred from the gynecologic oncology service, so
continuing consideration for chemotherapy or surgery was possible. All
patients had undergone surgery and chemotherapy before radiofrequency
ablation. Five patients had solitary metastatic lesions without other imaging
evidence of disease, and one patient had a dominant liver mass in the setting
of a small soft-tissue peritoneal nodule in the hepatorenal recess. Five of
the six tumors were along the periphery of the liver and were considered
implants from peritoneal seeding (International Federation of Gynecology and
Obstetrics stage III). The other tumor was intraparenchymal (stage IV). Three
of the six tumors were biopsy proven. The other three liver tumors were new
enlarging tumors in patients with ovarian cancer known to have previously
spread beyond the ovaries and out of the pelvis with the typical CT appearance
of low-density tumors at or adjacent to the liver surface.
In all cases the treatment rationale was to achieve local control.
Radiofrequency ablation was performed by one of three interventional
radiologists with experience in radiofrequency ablation of abdominal tumors.
Radiofrequency ablation was performed with CT (n = 5) or sonographic
(n = 1) guidance at the discretion of the radiologist performing the
procedure. Two radiofrequency ablation systems were available during this
period. The choice of system was at the discretion of the operator. A 200-W
generator with straight internally cooled single electrodes and pulsed current
was used in procedures on three patients (Cool-tip, Valleylab). A 150-W
generator with multitined expandable electrodes was used in procedures on four
patients (model 1500X, RITA). The choice of electrode was based on tumor size.
All tumors treated with straight internally cooled electrodes were 2.5 cm in
diameter or smaller, and a single electrode with a 2.0-cm active uninsulated
tip was used. Tumors treated with multitined 5-cm electrodes (StarBurst XL,
RITA) were smaller than 4 cm. For the tumor larger than 5 cm, a 7-cm electrode
allowing interstitial 3% saline instillation was used (StarBurst XLi, RITA).
For current dispersal, proprietary grounding pads were placed on both of the
patient's thighs according to manufacturer recommendations.
For both generator systems, overlapping ablations were performed, ranging
from one to three ablations per tumor (mean, 2.2 ablations). The electrode was
repositioned to cover the entire volume of tumor, including a small margin of
normal liver parenchyma for tumors in the liver. For liver tumors, the
radiofrequency ablation algorithm with internally cooled electrodes consisted
of pulsed current, each ablation lasting 12 minutes. With the 5-cm expandable
electrode, a temperature-based algorithm was used, the target temperature
being set at 105°C. Initial electrode deployment was set at 2 cm.
Subsequent deployments were expanded in 1-cm increments after the target
temperature was reached. At 4-cm and 5-cm deployment, the target temperature
was maintained for 7 minutes for each deployment. With use of the
saline-enhanced expandable electrode, 3% saline solution was infused through
the electrode at a rate of 0.05 mL/s for the duration of the ablation. An
incremental deployment algorithm, similar to that for the smaller electrode,
was used with 7-minute ablations at 6-cm and 7-cm diameters each.
If imaging after ablation showed residual disease as evidenced by residual
enhancement, additional ablation was considered in consultation with the
gynecologic oncology service. The decision to observe or to proceed with
additional ablation sessions was based on the prognosis of other disease when
present.
Radiofrequency ablation was generally performed as an outpatient procedure
with IV sedation consisting of 100-300 µg of fentanyl (Sublimaze, Janssen)
and 2-5 mg of midazolam (Versed, Baxter). In addition, 0.625 mg of droperidol
(Inapsine, Akorn) was used before 2001, when droperidol became unavailable.
Subsequent patients received 25-50 mg of meperidine (Demerol, Abbott
Laboratories) if needed. Radiofrequency ablation was performed early enough in
the day to allow time for most patients to recover completely from sedation
after 2-4 hours in the interventional radiology recovery area. One patient
needed admission after the procedure because of incomplete recovery from
sedation with persistent nausea.
Definitions for Reporting Results
Reporting of results was performed according to Society of Interventional
Radiology and Radiological Society of North America standards
[10]. Technique effectiveness
was defined as complete ablation of macroscopic tumor determined on imaging 3
months after treatment, thereby allowing additional ablation sessions if
needed to achieve complete necrosis. Primary effectiveness was defined as the
percentage of tumors successfully eradicated during the initial course of
treatment. Secondary effectiveness was defined as successful eradication by
repeated treatment of local tumor recurrence after complete ablation with the
initial treatment. Major complications were defined as those necessitating
unplanned hospitalization or intensive care unit admission, prolonging
hospital stay, or additional surgical or interventional procedures. Minor
complications were those managed conservatively but not necessitating or
prolonging a hospital stay.
Imaging
Postprocedure imaging was contrast-enhanced CT of the abdomen in all cases.
CT was performed 1 month after treatment for assessment of the initial result
of ablation and identification of residual tumor necessitating additional
radiofrequency ablation sessions. Absence of enhancement was considered to
represent complete necrosis on the basis of previous results with liver and
renal tumors and was assessed both visually and quantitatively. Residual tumor
enhancement within or at the periphery of the target tumor was considered
viable tumor. Additional CT was performed 3 months after treatment and then at
3-month intervals with the timing altered if needed to accommodate management
of new disease. The evolution of the size of the zone of ablation was
monitored with serial CT and is reported as orthogonal diameter in the axial
plane in which the zone of ablation was the largest. In the single case in
which CT scans were difficult to interpret definitively, FDG PET was
performed. Images were reviewed by consensus of two experienced
radiologists.
Results
Local Control and Imaging Findings
Tumor details, duration of follow-up, and evolution of the zone of ablation
are shown in Table 1. After a
single session, radiofrequency ablation resulted in complete necrosis (Figs.
1A,
1B,
1C, and
1D) according to imaging
criteria in five of the six patients for a technique effectiveness rate of
83%. The one patient with persistent peripheral nodular enhancement at the
edge of a 3.2-cm tumor also had new metastasis in the hepatorenal recess, left
upper quadrant, and pelvis at the first CT examination after radiofrequency
ablation. Because the disease was so extensive, ablation was not repeated.
On subsequent imaging, four of the five tumors had no evidence of local
progression over a follow-up period of 8 months to 3.3 years (mean, 23 months)
for a primary efficacy rate of 80%. The patient with the 5.3-cm hepatic
metastatic lesion had marked involution of the zone of ablation, but a small
area of possible enhancement along the inferior margin was confirmed with FDG
PET 9 months after treatment (Figs.
2A,
2B,
2C,
2D,
2E,
2F, and
2G). The patient underwent
repeated treatment with single placement of a straight internally cooled
electrode with a 2-cm active tip. There was no tumor enhancement for another
16 months, for a secondary efficacy rate of 100%.
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Fig. 2D —80-year-old woman with 5.3-cm hepatic metastatic lesion from
ovarian cancer. Enhanced CT scan 9 months after radiofrequency ablation along
caudal aspect of zone of ablation (arrow) shows that this area is
slightly denser, raising possibility of enhancement versus volume-averaging
artifact.
|
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Fig. 2F —80-year-old woman with 5.3-cm hepatic metastatic lesion from
ovarian cancer. FDG PET scan after second ablation session shows absence of
uptake in zone of ablation (arrow), confirming complete
treatment.
|
|
Tumor Markers
CA 125 results were available before and after radiofrequency ablation in
five cases. In four of the five patients CA 125 level was normal both before
and after ablation. In the fifth patient, CA 125 level was elevated before
radiofrequency ablation and was even higher 4 months after ablation, when she
presented with adenopathy.
Patient Outcome
The patient with incomplete necrosis and early development of new
metastasis underwent chemotherapy and died 7.8 months after ablation. Of the
five patients with complete ablation of the target lesion, one had limited
adenopathy at the time of ablation, for which she underwent chemotherapy. In
the other four patients, new foci of disease developed remote from the target
tumor 1 month to 4 years after ablation. These additional sites of disease
were not amenable to radiofrequency ablation because of diffuse extent of
disease or proximity to bowel or ureter and were managed with surgery
(n = 1) or chemotherapy (n = 3). One patient died 2.3 years
after radiofrequency ablation. Four patients were alive 8 months to 3.3 years
after ablation.
Complications
There were no major complications. The one minor complication was a small
second-degree skin burn in the anterior abdomen just anterior to the target
liver tumor. This complication occurred with use of the 7-cm expandable
electrode with saline instillation but not at the skin entry site. Instead, a
small portion of the ablation zone extended to the skin surface, presumably
from diffusion of saline solution to the subcutaneous tissues. The burn healed
with conservative treatment provided in consultation with the burn
service.
Discussion
Scattered reports of the use of radiofrequency ablation in the management
of focal metastatic lesions of ovarian cancer have appeared either as case
reports or as cases in larger series of hepatic metastatic lesions, limiting
evaluation of this technique in the management of ovarian cancer
[6-9,
11]. To our knowledge, this
report is the first to describe only isolated metastatic lesions of ovarian
cancer managed with radiofrequency ablation. Our findings confirm an excellent
rate of local control with no local progression of disease over a mean period
of 2.5 years. Absence of enhancement and decrease in the size of the zone of
ablation were seen in all but one patient in our series and provide a useful
imaging marker of success.
As promising as these results are for local control, the role of
percutaneous radiofrequency ablation in ovarian cancer remains limited. The
disease commonly manifests itself along multifocal serosal surfaces, limiting
the utility and safety of local hyperthermic therapy. In addition, there
remains controversy within the gynecologic oncology literature as to the exact
effect of cytoreduction on survival. Rose et al.
[12] found little to no
benefit of surgical cytoreduction in survival or progression-free survival.
Other authors
[1-4]
reached different conclusions. Their findings support cytoreduction and thus
indirectly support local tumor ablation in cases of isolated disease.
Our promising results in achieving local control in selected patients
expand on the few cases described in the literature. Jacobs et al.
[8] reported on a case of
granulosa cell ovarian tumor metastatic to the liver successfully treated with
radiofrequency ablation. In a series of 10 patients with liver metastasis
managed with percutaneous MRI-guided radiofrequency ablation, Mahnken et al.
[7] included one successfully
treated patient with ovarian carcinoma. In the largest series, Bleicher et al.
[11] described radiofrequency
ablation of liver tumors in 153 patients, 3.9% of whom had ovarian cancer.
That report, however, is scant on details specific to patients with ovarian
cancer and includes open, laparoscopic, and percutaneous approaches. We
focused on the percutaneous approach, defining a cohort of patients with
limited macroscopic disease and therefore no other indication for
cytoreductive surgery. Bojalian et al.
[6], in their case report of a
solitary hepatic metastatic lesion managed percutaneously, advocate the
percutaneous approach for patients similar to ours. However, those authors
emphasize that an open approach should be considered in cases of liver
metastasis that would be difficult to resect but in which cytoreduction for
extrahepatic disease necessitates surgery, thereby addressing all of the
disease in a single procedure.
Concerning our cohort of patients, an argument can be made that
radiofrequency ablation allows the test of time approach advocated by Livraghi
et al. [5] in the care of
patients with metastatic colon cancer. The test of time approach involves
management of resectable liver lesions with percutaneous radiofrequency
ablation with close imaging surveillance in an effort to minimize the number
of hepatic resections that prove of little to no benefit to the patient either
because the cancer rapidly progresses at sites remote from the target tumor or
because the patient continues to have no evidence of disease progression
anywhere. In cases of isolated metastatic lesions of ovarian cancer,
percutaneous radiofrequency ablation allows deferral of surgery and
chemotherapy for varying periods. Although most patients in our series did not
undergo subsequent surgery, radiofrequency ablation did allow delay of
chemotherapy in patients with new disease that was slow to manifest
itself.
Our single complication was minor but raises concern about the use of
saline instillation to augment tumor necrosis in radiofrequency ablation.
Saline-augmented ablation zones are known for their irregularity resulting
from inhomogeneous diffusion of saline solution. In tumors close to vital
structures or to the skin surface, saline diffusion to these structures can
predispose them to thermal injury. The manufacturer has decreased the
recommended saline concentration from 3% to 0.9%, but the effect of this
adjustment on the likelihood of burning nontarget tissues is not known.
Despite the limited cohort of patients with ovarian cancer who are
candidates for local ablative therapy, ovarian cancer remains prevalent, and
interventional radiologists can expect to see occasional patients who may
benefit from this therapy. Familiarity with the disease presentation,
treatment options, and treatment rationale allows appropriate patient
selection.
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Abstract
Introduction
