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Skeletal Radiol (2006) 35: 1–15
DOI 10.1007/s00256-005-0003-2
REVIEW ARTICLE
Matthew R. Callstrom
J. William Charboneau
Matthew P. Goetz
Joseph Rubin
Thomas D. Atwell
Michael A. Farrell
Timothy J. Welch
Timothy P. Maus
Received: 28 December 2004
Revised: 6 June 2005
Accepted: 7 July 2005
Published online: 5 October 2005
# ISS 2005
Image-guided ablation of painful metastatic
bone tumors: a new and effective approach
to a difficult problem
Abstract Painful skeletal metastases
are a common problem in cancer pa-
tients. Although external beam radia-
tion therapy is the current standard of
care for cancer patients who present
with localized bone pain, 20–30% of
patients treated with this modality do
not experience pain relief, and few
further options exist for these patients.
For many patients with painful meta-
static skeletal disease, analgesics
remain the only alternative treatment
option. Recently, image-guided
percutaneous methods of tumor
destruction have proven effective for
treatment of this difficult problem.
This review describes the application,
limitations, and effectiveness of
percutaneous ablative methods
including ethanol, methyl methacry-
late, laser-induced interstitial thermo-
therapy (LITT), cryoablation, and
percutaneous radiofrequency ablation
(RFA) for palliation of painful skeletal
metastases.
Keywords Metastases
.
Bone
.
Palliation
.
Ablation
.
Percutaneous
Introduction
Image-guided percutaneous methods of tumor destruction
have rapidly evolved and proven effective for treatment of
benign skeletal lesions and, more recently, for palliation of
painful metastatic skeletal disease. Treatment of primary
bone tumors is largely restricted to benign lesions, such as
osteoid osteomas, as a single modality treatment or as an
adjunct to surgical resection [1–4]. The use of ablation
techniques for treatment of painful metastatic disease has
evolved because of the often disabling pain cancer patients
experience, despite the use of conventional therapies
including external beam radiation and narcotic analgesics.
Skeletal metastases are a common problem in cancer
patients. Autopsy studies have shown that up to 85% of
patients that die from breast, prostate and lung cancer have
bone metastases at the time of death [5]. Complications due
to skeletal metastases, including pain, fractures, and de-
creased mobility, can often affect a patient’s quality of life,
ultimately reducing performance status [5, 6]. In addition,
these complications can affect a patient’s mood, leading to
associated depression and anxiety [5]. Current treatment
for patients with bone metastases are primarily palliative
and include localized therapies (radiation and surgery), sys-
temic therapies (chemotherapy, hormonal therapy, radiophar-
maceuticals, and bisphosphonates) and analgesics (opioids
and non-steroidal anti-inflammatory drugs).
Skeletal metastases that cause pain but that are also at
risk for impending fracture may be treated surgically with
an intramedullary rod or other internal fixation in an
extremity. However, lesions located in the spine and peri-
acetabular regions require greater surgical intervention to
effect stabilization. Recently, percutaneous methods have
been developed to stabilize these types of lesions through
the administration of methyl methacrylate into the tumor,
with or without prior treatment with ablative methods.
The causes of pain in patients with bone metastases are
not fully understood, and the presence of pain is not
correlated with the type of tumor, location, number or size
of metastases [6–8]. Possible mechanisms of pain include
(1) stretching of the periosteum secondary to tumor growth,
(2) fractures (both micro-fractures and macro-fractures),
(3) cytokine-mediated osteoclastic bony destruction, re-
sulting in stimulation of nerve endings in the endosteum
M. R. Callstrom (*)
.
J. W. Charboneau
.
T. D. Atwell
.
M. A. Farrell
.
T. J. Welch
.
T. P. Maus
Department of Radiology, Mayo Clinic,
Rochester, MN, USA
e-mail: callstrom.matthew@mayo.edu
M. P. Goetz
.
J. Rubin
Department of Oncology, Mayo Clinic,
Rochester, MN, USA
[9–15], and (4) tumor growth into surrounding nerves and
tissues.
External beam radiation therapy (RT) is the current
standard of care for cancer patients who present with
localized bone pain. This treatment results in a reduction in
pain for the majority of these patients; however, 20–30% of
patients treated with this modality do not experience pain
relief, and few options exist for these patients [16–21].
Unfortunately, patients who have recurrent pain at a
metastatic site previously irradiated are often not eligible
for further RT secondary to limitations in normal tissue
tolerance. Additionally, metastatic disease in this patient
population is often refractory to standard chemotherapy or
hormonal therapy. Surgery, which is usually reserved for
impending fracture, is not always an option when patients
present with advanced disease and poor functional status.
Radiopharmaceuticals, which have known benefit in
patients with diffuse painful bony metastases, are not
considered a standard of care for patients with isolated,
painful lesions. For many patients with painful metastatic
disease, analgesics remain the only alternative treatment
option. Unfortunately, in order to obtain sufficient pain
control for many of these patients, side effects such as
constipation, nausea, and sedation, can be significant.
Percutaneous therapies for palliation of painful
metastases
Because of the shortcomings of the currently available
therapies for many patients with painful metastatic disease,
investigators have explored alternative treatment strategies.
Transcatheter embolization of skeletal neoplasms has been
found as a helpful adjunct to surgery to minimize blood
loss. These treatments may also relieve neurological com-
promise and pain [22–24] and have been reviewed else-
where [25]. Several new treatment strategies have recently
been reported for the treatment of painful metastatic
disease. All these new methods are based on the use of
percutaneous image-guided methods to deliver tissue
ablative materials or devices into focal metastatic lesions.
These methods include the use of ethanol, methyl meth-
acrylate, laser-induced interstitial thermotherapy (LITT),
cryoablation, and percutaneous radiofrequency ablation
(RFA). The device-based ablation methods may also be
combined with the use of methyl methacrylate for stabi-
lization of bones at significant risk of fracture.
Percutaneous ethanol therapy
Gangi and colleagues described the use of CT-guided
percutaneous administration of 95% ethanol for the
palliation of pain from 27 metastatic bone lesions in 25
patients previously treated with radiotherapy and/or che-
motherapy [26]. Sixteen lesions received a single dose of
ethanol, while ten lesions received two doses and one
lesion received three doses. The response of these patients
to this treatment was assessed by the reduction in use of
analgesic medicines 48 h and 2 weeks following therapy.
Complete relief of pain was achieved in four patients, and
very good but incomplete relief (75% analgesic medicine
reduction) in 11 patients. Seven patients received little or
no relief with the treatment.
Percutaneous methyl methacrylate treatment:
acetabular and vertebral body lesions
Percutaneous delivery of methyl methacrylate has been
used to palliate pain in patients with vertebral body
neoplasms and to prevent pathological fractures [27–32].
The injection of bone cement into the vertebral body lesion
results in reduction in pain and also provides stabilization
of the involved bone. The approach used for treatment of
malignant lesions in a vertebral body is identical to that
used for treatment of painful insufficiency fractures of the
spine.
For example, a patient was treated in our center for pain
due to a thoracic vertebral body compression fracture
resulting from metastatic myeloma. Under biplane fluo-
roscopy, a 13 G bone biopsy needle is advanced through
the center of a pedicle into the vertebral body and the
malignant lesion (Fig. 1). Intraosseous venography may be
performed to exclude direct venous continuity to central or
epidural veins, although the benefit of this imaging is
debated due to potential poor visualization of bone cement
from pooled residual contrast [27, 31, 33–38]. Barium
sulfate and possibly an antibiotic are mixed with methyl
methacrylate powder. Liquid monomer is added to the
powder to form a tooth-paste consistency. The material is
then injected under fluoroscopic control until it fills the
lesion without leakage into the disk space or perivertebral
tissues, with constant vigilance for undesired leakage into
veins, neural foramina, epidural space or joints.
Weill and colleagues used percutaneous injection of
methyl methacrylate cement to treat 37 patients with 52
procedures for spinal metastases causing pain (33/37) or in
order to stabilize a vertebral body (4/37). Vertebroplasty
was performed alone in 25 sessions and combined with
surgery and/or radiation therapy in the remainder of
treatments. By Kaplan–Meier analysis, they estimated
that 73% and 65% of the patients had durable pain relief at
6 months and 1 year, respectively, as defined by a 50%
reduction in narcotic analgesic use or the use of non-
narcotic analgesia for pain relief [27]. Gangi and col-
leagues described the treatment of 36 vertebral body and 12
acetabular malignancies, with 85% of patients deriving
moderate relief (decreased pain score ≥2/10) within 12–
48 h of the treatment [29]. Deramond and colleagues
reported the treatment of 101 patients at risk for vertebral
body collapse due to malignancy. They found an improve-
2
ment in patient quality of life in more than 80%. These
authors recommend radiation therapy following adminis-
tration of methyl methacrylate, as radiation complements
the analgesic effect of methyl methacrylate. Local recur-
rence is rare following the procedure, even without
additional radiation therapy [31].
Methyl methacrylate has also been used for the treatment
of periacetabular metastases. In our center we treat
periacetabular metastases for pain or for lesions, that, with
progression, would likely lead to fracture. Our approach for
these periacetabular metastases has been first to ablate the
lesion, with either cryoablation or radiofrequency ablation,
followed the next day by the cementoplasty procedure. For
example, this approach was used to treat a 65-year-old man
with a painful metastatic lesion involving the left periace-
tabular region (Fig. 2). This patient experienced complete
pain relief, which has been sustained for 11 months. He has
also been able to avoid both a fracture and the morbidity
associated with operative acetabular stabilization.
Others have used cementoplasty alone to treat periace-
tabular metastases, lower extremity lesions, and pelvic
bone metastases [29, 39–43]. Cotten and colleagues treated
12 periacetabular metastases in 11 patients that could not
be treated surgically because of the location, extent, or
number of the metastases or because of the patients’
associated comorbidities [ 39, 40]. Each patient also
underwent radiation therapy an average of 21 days fol-
lowing the procedure. The authors found an improvement
in pain in most patients soon after the procedure that was
sustained in nine patients and improved walking in each
patient an average of 3 days following the procedure. One
patient subsequently suffered an acetabular fracture with
increased pain. Bone cement leaked into the joint space in
one patient, with transitory increased pain but with no
impact on subsequent pain relief or walking improvement.
Hokotate and colleagues reported percutaneous adminis-
tration of methyl methacrylate for a painful periacetabular
hepatocellular carcinoma metastasis that was unresponsive
Fig. 1 Fluoroscopic spot films
of the lower thoracic spine. A
Bone biopsy device aligned
along the right pedicle of a
slightly compressed vertebral
body. B Bone biopsy device
placed in the mid-vertebral
body, with contrast injection
demonstrating venous commu-
nication. The device is advanced
slightly, with no subsequent ve-
nous enhancement. C,D Injec-
tion of methyl methacrylate with
excellent spread of material
3
to chemoembolization and radiation therapy. This patient
obtained pain relief, within 1 day of the treatment, which
persisted for 3 months until the patient’s death [41]. Marcy
and colleagues described the use of bone cement for the
treatment of 18 patients with painful metastatic lesions in
the acetabulum, iliac bone, and sacrum [42]. They found
mild–moderate pain relief at 1 month follow-up and
improved walking in all but two patients. One patient
suffered an acetabular fracture 15 days following the
procedure. Hierholzer and colleagues reported substantial
immediate pain relief, in five patients with painful
metastases to the pelvis and femur, following injection of
bone cement with elimination of the need for pain
medication in the follow-up period [43].
Percutaneous laser-induced interstitial thermotherapy
Gröenemeyer and colleagues reported the treatment of
three patients, with spinal metastases, using a Nd:YAG
laser with a wavelength of 1,064 and a 400 μm fiber [44].
With local anesthesia and CT guidance, a coaxial system
was used via a transpedicular approach. Laser energy was
applied at a power of 4–10 W with a pulse length of 0.1 –
1.0 s at 1 s intervals. In order to achieve coverage greater
than 7 mm, the fiber was repositioned and the thermal
treatment repeated, completing the procedure in 60–
90 min. Three months after treatment, the patients had
45%, 30%, and 35% pain reduction.
Percutaneous cryoablation
Cryoablation has a long history of successful treatment of
neoplasms in several organs, including prostate, kidney,
liver, and the uterus. First-generation devices were limited
to intraoperative use because of their large diameter, the use
of liquid nitrogen for tissue cooling, and the lack of well-
insulated probes. Newly developed percutaneous cryo-
probes are based on delivery of argon gas through a
segmentally insulated probe, with rapid expansion of the
gas that results in rapid cooling, reaching −100°C within a
few seconds. The use of sealed cryoprobes with small
diameters (1.7 mm and 2.4 mm) and with insulation along
the shaft allows the use of these devices either percuta-
neously or intraoperatively. Active thawing of the ice ball is
achieved by the active instillation of helium gas, instead of
argon gas, into the cryoprobes. The Endocare Incorporated
(Irvine, Calif, USA) system allows the independent oper-
ation of up to eight cryoprobes at a time. A single cryoprobe
Fig. 2 Pain palliation and sta-
bilization of a non-small cell
lung cancer metastatic lesion,
involving the periacetabular re-
gion, using cryoablation fol-
lowed by cementoplasty. A
Non-contrast-enhanced CT of
the pelvis demonstrates an os-
teolytic lesion in the left supra-
acetabular region. The patient
had difficulty walking without
the use of a cane prior to the
procedure. B Non-contrast CT
of the pelvis showing two
cryoprobes placed into the le-
sion. C Non-contrast CT of the
pelvis immediately following
removal of the cryoprobes
shows the low attenuation
ice ball encompassing the ma-
lignant lesion. D 3D volumetric
image showing methyl meth-
acrylate cement filling the
supra-acetabular defect. The pa-
tient also received 3,000 cGy in
ten fractions. The patient con-
tinues to be pain-free and is
walking normally 11 months
after the treatment
4
provides an ice ball of approximately 3.5 cm diameter. A
great advantage of the cryoablation systems is that the use of
multiple cryoprobes allows the generation of large ice balls
(>8 cm diameter), possible shaping of the ablation zone
through varied geometry of probe placement, and decreased
procedure time for large lesions by avoiding the need to
perform the time-consuming overlapping ablations needed
with other ablation techniques. Importantly, synchronous
ablation with several cryoprobes eliminates possible resid-
ual disease that can result from the use of overlapping
ablation at the single ablation interfaces [45].
Cell death from cryoablation is due to two causes. First,
rapid freezing immediately adjacent to the probe results in
intracellular ice formation and subsequent cell destruction.
At a further distance from the probe, relative gradual
cooling causes osmotic differences across the cell mem-
brane, with secondary cellular dehydration and death.
Given relative cellular tolerance to freezing temperatures,
cell death occurs within about 3 mm internal to the ice ball
margin [46, 47].
Preliminary data suggest that cryoablation is effective in
treating painful primary and secondary bone neoplasms
[48]. In this preliminary work, 16 tumors in 14 patients were
treated with percutaneous cryoablation using MR guidance.
These investigators reported a significant reduction in
patients’ pain in the immediate postoperative period. This
pain relief continued over the long term, with associated
significant improvement in patients’ quality of life.
As part of an on-going prospective clinical trial, we have
treated ten patients with painful metastatic disease involv-
ing bone. This effort involves treating patients who have
one or two painful lesions that cause ≥4/10 pain in a 24 h
period. We are assessing patients pain regularly over a 2
year period, using the Cleeland Brief Pain Inventory [49,
50], a validated visual analogue scale for assessment of
patient pain. Although statistical evaluation is premature,
preliminary data are encouraging.
As an example of the successful use of percutaneous
cryoablation, we treated a patient with a single painful
metastatic focus of paraganglioma involving the left cla-
vicular head. Unfortunately, this patient also suffered from
Fig. 3 Metastatic para-
ganglioma involving the
clavicular head treated with
cryoablation. A Non-contrast
CT demonstrates an osteolytic
lesion involving the left clavicle.
The lesion caused 7/10 worst
pain in a 24 h period prior to
treatment. B 3D volumetric CT
scan showing two cryoprobes
placed into the lesion. C Worst
and average pain scores over a
24 h period at baseline and over
a 2 year follow-up period
5
the systemic effect of the catecholamine-releasing tumor,
with palpitations and elevated blood pressure. Following
appropriate premedication with metoprolol, phenoxyben-
zamine and metyrosine, two crossing probes were placed
into the lesion, with both ultrasound and CT guidance. An
ice ball was generated that completely encompassed the
lesion (Fig. 3). The patient experienced excellent durable
reduction in her pain and also, importantly, her catechol-
amine levels returned to normal and her blood pressure
stabilized.
Another example of the use of cryoablation involved a
patient with metastatic ovarian cancer who presented with
7/10 pain in the right groin region. CT examination found a
small metastatic lesion in the right pelvis (Fig. 4).
Unfortunately, at the time of ablation of this pelvic
metastasis, the right colon was in contact with the lesion.
We attempted to displace the colon with sterile water;
however, the displacement was insufficient to allow a safe
ablation. An important advantage of cryoablation over high
temperature ablation methods is the option to use tissue
displacement devices such as balloons to avoid damaging
adjacent normal tissue. This approach was successful, as
deployment of a small balloon allowed safe ablation to be
performed. This patient experienced mild transient perineal
pain, which resolved over a 4 week period. She also
reported marked improvement in her typical pain, with a
great improvement in her quality of life over a 2 year period
of follow-up.
Percutaneous radiofrequency ablation
Recently, several case reports have appeared that describe
the treatment of painful metastatic lesions with percutane-
ous radiofrequency ablation. Included below are descrip-
tions of several of these case reports. Following this, we
include a summary of results of a completed prospective
clinical trial designed to determine the clinical magnitude
and durability of the use of radiofrequency ablation for the
treatment of painful metastatic disease involving bone.
Fig. 4 Metastatic ovarian can-
cer abutting the right iliac bone,
resulting in 7/10 worst pain in a
24 h period prior to treatment. A
Contrast-enhanced CT of the
pelvis demonstrates a metastatic
mass in the right pelvis. B Non-
contrast CT of the pelvis show-
ing two cryoprobes placed into
the lesion, with an ice ball
encompassing the lesion. A
balloon was deployed at the
time of the procedure to displace
the adjacent ascending colon
(arrows). C Worst and average
pain scores over a 24 h period
at baseline and over a 2 year
follow-up period
6
Percutaneous radiofrequency ablation: case reports
and series
As a prelude to treatment of spinal metastatic disease,
Dupuy and colleagues used a pig model to examine the
temperature distribution within a vertebral body and the
adjacent spinal canal, with the radiofrequency ablation
electrode placed within the vertebral body [51]. They found
decreased heat transmission in cancellous bone and an
insulative effect of cortical bone. Importantly, temperature
elevations in the epidural space were not high enough to
cause injuries to the adjacent spinal cord. Subsequently,
these workers reported the treatment of a woman with a
painful osteolytic focal metastatic hemangiopericytoma
lesion in the anterior aspect of a lumbar vertebral body.
Using local anesthesia and conscious sedation, the authors
accessed the lesion using a far lateral approach, passing
through intact cortex with a 14-gauge Ackermann bone
biopsy needle (Cook, Bloomington, Ind., USA). Subse-
quently, a 3 cm exposed-tip Radionics radiofrequency
electrode (Tyco Healthcare Group LP, Burlington, Mass.,
USA) was used to treat the lesion. The patient had improved
pain control at the latest follow-up evaluation of 13 months.
It is important to note that careful patient selection is
important in the treatment of vertebral body lesions. Intact
bone provides at least partial insulation of the spinal canal
from excessive heat. However, if cortical destruction is
present this insulative barrier is also destroyed, and spinal
cord or major nerve injury may result if ablation is
performed in this region.
Gröenemeyer and colleagues reported the radiofre-
quency ablation treatment of ten patients with 21
unresectable painful spinal metastases, using an expand-
able-type electrode (RITA Medical Systems, Mountain
View, Calif., USA) with a 50 W generator. The patients
were treated with local anesthesia only. Target temperature
for the ablations was chosen on the basis of distance from
the spinal cord and patient tolerance for the procedure.
Four of the patients were also treated with vertebroplasty,
receiving 3–5.5 ml of polymethyl methacrylate 3–7 days
following radiofrequency ablation [52]. At last follow-up,
nine of the ten patients reported reduced pain, with an
average pain reduction of 74%. Although it may be
possible to treat selected patients with local anesthesia, in
most cases a minimum of conscious sedation is necessary,
and, for many patients, general anesthesia is indicated for
adequate pain control.
Patti and colleagues reported the treatment of a patient
with metastatic fallopian tube carcinoma with multiple
painful subcutaneous masses [53]. Using conscious seda-
tion and local anesthesia, they treated the lesions for 10 min
at a target temperature of 110°C with a model 70 electrode
and 50 W generator. Immediately following treatment, the
patient had no pain at the treated sites and reported 1–3/10
pain 1 month later.
Ohhigashi and colleagues reported the RF ablation
treatment of painful recurrent rectal cancer in the pelvis
[54]. Notably, recurrent rectal cancer may produce local
pain, rectal bleeding, or bowel obstruction, with resultant
poor quality of life. Although a curative approach, such as
total pelvic exenteration, is possible, few patients are
eligible for this treatment [55]. Unfortunately, radiation
therapy is palliative only and of limited clinical benefit [56].
These workers treated two patients with 4 cm diameter and
6 cm diameter recurrent rectal carcinomas located anterior
to the sacrum, which had not responded to chemotherapy or
radiation therapy. Using epidural catheter mediated anal-
gesia, they placed a LeVeen RF electrode (Boston Scientific
Corp., Tokyo, Japan) into the lesions using CT guidance.
Both patients reported a decrease in pain following the
treatment and a reduction in oral analgesic requirements.
Schaefer and colleagues described the combined use of
percutaneous radiofrequency ablation, with subsequent
administration of bone cement, for a painful pathological
fracture of the tibial plateau. The patient was able to resume
walking 1 day after the procedure, and follow-up imaging
at 3 months showed no change in the position of the bone
cement [57].
Percutaneous radiofrequency ablation: clinical trial
Because of the several reports suggesting the potential
benefits of RFA for palliation of pain from metastatic
disease, we conducted and published the results a feasibility
clinical trial to determine the safety and benefits of RFA in
patients with painful metastatic lesions involving bone [58].
Our preliminary data showed that this procedure was safe
and resulted in significant relief of pain; therefore, the study
was expanded to enroll patients from other centers in the
United States of America and Europe. We reported an
analysis of the multicenter trial data following the treatment
of 43 patients, again finding highly significant reductions in
patient pain following treatment with radiofrequency
ablation [59, 60].
The completed multicenter trial involved the treatment
of 62 patients at five centers in the USA and Europe over a
2 year period. Patients that were included had ≥4/10 worst
pain over a 24 h period from ≤2 painful sites of metastases
based on the Brief Pain Inventory (BPI) [49, 50 ]. In the
BPI, patients are asked to rate their worst, least and average
pain in the past 24 h, with allowed responses ranging from
0 to 10 (0 = no pain, 10 = pain as bad as you can imagine).
Relief of pain secondary to the RFA procedure or to pain
medication is scored on a scale of 0% (no relief) to 100%
(complete relief). Pain interference with daily living is
evaluated by questions concerning general activity, mood,
walking ability, normal work, relations with other people,
sleep, and enjoyment of life, also on a 0–10 scale (0 = no
interference, 10 = completely interferes).
7
Patients were treated under conscious sedation or
general anesthesia at the discretion of the individual
investigator. All patients included in the study were treated
with a Starburst XL model needle (RITA Medical Sys-
tems), a 14 gauge/6.4 Fr device, with an active electrode
trocar tip and nine electrodes spread in a ball-like fashion
that generates up to a 5 cm diameter zone of necrosis
(Fig. 5).
Immediate post-procedural pain has been treated with
epidural or intravenously administered opioid analgesics.
Depending on the size of the treated lesion and the degree
of post-operative pain, patients were typically observed
overnight in the hospital. Patients with persistent post-
procedural pain were switched to oral opioid analgesics at
the time of discharge.
Representative cases and lessons learned
Importance of treatment of the bone–tumor interface
Figure 5 shows the needle fully deployed, and deployment
of the tines into an osteolytic lesion in the periacetabular
region. This figure illustrates that the electrode is advanced
into the soft-tissue portion of the lesion to be treated and the
tips of the tines of the electrode are placed against the soft-
tissue/bone interface. Figure 6 shows another example of
an osteolytic lesion that involves the L5 vertebral body,
with associated partial destruction. The RF electrode is
placed with the tines driven against the bone–soft tissue
interface. Subsequent electrode deployments (not shown)
are performed to completely treat the portion of bone in-
volved in the destructive metastatic lesion. Electrode de-
ployment diameters are chosen to cover the metastatic
lesion adequately without damaging nearby normal, uni-
nvolved tissues.
In other centers some lesions have been treated with
placement of the electrode into the center of the lesion with
resultant debulking of the lesion but with incomplete
ablation of the soft-tissue bone interface. Figure 7 shows a
large osteolytic metastatic lesion involving the sacrum 6
weeks following RF ablation. This image shows central
low attenuation within the metastatic lesion consistent with
necrosis from the RF ablation procedure. Residual tumor is
clearly present along the medial aspect of the sacrum and
against the adjacent iliac bone. Following this treatment,
the patient failed to derive reduction of pain and received
no clear benefit from the procedure.
Importance of localizing source of pain
It is critically important to examine each patient prior to the
RF ablation treatment to determine whether the patient ’s
pain corresponds to an identifiable lesion on CT, MRI, or
US imaging. Figure 8 shows a prone CT scan of a metas-
tatic osteolytic lesion involving the mid-sacrum. The pa-
tient was examined, and a metallic marker was placed on
the skin overlying the site of greatest pain. As shown in
Fig. 8, the site of pain corresponded to a sacral fracture on
Fig. 5 A RF ablation electrode
with full deployment
(Starburst XL electrode, RITA
Medical Systems). B CT scan
with RF ablation electrode de-
ployed in an osteolytic lesion in
the acetabular region
Fig. 6 RF ablation treatment of the bone–tumor interface. CT
demonstrates osteolytic destruction involving the left aspect of the
L5 vertebral body. The electrode is deployed with the tines engaging
the destroyed margin of the involved bone. Incidentally noted is an
old pars interarticularis fracture on the right. The bone–tumor
interface is a key site for electrode deployment in order to destroy
nerve endings that are a likely cause of pain
8
the side opposite the destructive sacral lesion. Because the
patient’s pain likely resulted from the underlying sacral
fracture, we did not treat the adjacent destructive sacral
lesion.
Painful metastases involving the sacrum
Patients who have locally recurrent metastatic rectal
carcinomas involving the sacrum or the presacral space
often have pain associated with their disease. Several
patients were treated for recurrent or residual metastatic
rectal carcinoma centered anterior to the sacrum in the
presacral space, often with associated osteolytic destruc-
tion of the underlying sacrum. Figure 9 shows a typical
lesion in a 38-year-old man, measuring approximately
3 cm in diameter and located at the level of the coccyx,
with 8/10 pain. The patient’s pain had decreased to 2/10
at week 4, and he reported 1/10 pain at the treated site at
the latest follow-up interview, 24 months following
treatment.
Remarkably, even large painful lesions may be treated
effectively with RF ablation. Figure 10 shows a portion of a
destructive infiltrative metastatic rectal carcinoma lesion
involving the sacrum. This lesion measured approximately
11 cm in diameter and involved the majority of the sacrum.
Figure 10A is a CT scan at the level of the lower sacrum
that shows the large destructive lesion. The patient was
unable to sit or lie on his back due to severe pain, which he
rated as 8/10. Prior treatments included resection of the
Fig. 7 Failed palliation of pain due to RF ablation treatment of the
central portion of a metastatic lesion without treatment of the tumor–
bone interface. CT performed 6 weeks after RF ablation demon-
strates necrosis in the treated central portion of the tumor, with
moderate residual tumor involving the sacrum and iliac bone. To be
effective, the RF ablation treatment should be at the tumor–bone
interface. Debulking of the central portion of metastatic lesions is
not effective in reducing pain
Fig. 8 Importance of determining exact site of pain. In this case
pain is due to a sacral fracture rather than osteolytic tumor. Prior to
CT examination, the patient was examined, and a metallic marker
(arrow) was placed on the skin overlying the site of focal pain. CT
scan shows an osteolytic destructive lesion, involving the sacrum,
opposite a sacral fracture (arrowhead). This lesion was not treated,
as the patient’s pain was more likely due to the sacral fracture than to
the adjacent osteolytic lesion
Fig. 9 Metastatic presacral rectal carcinoma. A Prone contrast-
enhanced CT demonstrates a peripherally enhancing soft-tissue
mass anterior to the coccyx. B Prone CT demonstrates the RF
ablation electrode deployed within the mass. The patient’s pain had
decreased from 8/10 to 1/10 4 weeks after treatment. The patient
continued to report 0–1/10 pain at this site 24 months after treatment
9
rectum with a diverting colostomy. The patient had reduced
bladder function that he described as difficulty with
initiation of voiding and incomplete emptying of his
bladder. Because there was the desire to retain the patient’s
bladder function, the lesion was treated in two stages, 6
weeks apart, with a total of 14 electrode deployments, with
the initial treatments focused on the caudal aspect of the
sacrum. Figures 10C and D show two of the seven RF ablation
Fig. 10 RF ablation of a large
sacral metastasis. A,B Prone CT
demonstrates near-complete re-
placement of the sacrum by
metastatic rectal carcinoma. C,D
RF ablation electrodes deployed
to 5 cm. These were two of
seven electrode placements dur-
ing the first of stage of treatment
for the ablation of much of the
caudal aspect of the osteolytic
lesion. The second-stage treat-
ment of the mid-sacrum was
performed 6 weeks later. The
patient was unable to sit prior to
treatment and had resting pain
of 8/10. One day following the
ablation the patient was able to
sit. His pain had decreased to
3/10 following the first stage
and to 0/10 soon after the sec-
ond stage of treatment
Fig. 11 Metastatic colorectal
carcinoma involving rib, verte-
bral body and pleural surface. A
Prone CT demonstrates osteo-
lytic destruction of the lateral
portion of the vertebral body,
with associated soft-tissue mass
anterior to the rib. B Prone CT
scan shows the passive thermo-
couple probe placed near the
vertebral body pedicle with the
RF electrode deployed laterally
in the metastatic lesion. Abla-
tion was discontinued when the
temperature at the passive ther-
mocouple reached 40°C. C
Photograph of the RF ablation
electrode in place, with adjacent
thermocouple located medially.
The patient’s pain had decreased
from 10/10 to 3/10 4 weeks
after the treatment
10
electrodes at the first stage of the treatment. Following the
initial treatment, the patient was able to sit in bed the same
day and described 3/10 pain in the treated region 4 weeks
following the procedure. Because of the patient’s desire for
greater pain relief, and with the understanding that further
RF ablation could lead to loss of bladder function, we
treated the superior portion of the lesion up to the level of
the S2 neural foramina. Within 4 weeks, his pain had
decreased to 0/10 at the treated region, and, fortunately, his
bladder function was not disturbed by the treatment.
RF ablation of painful paraspinal lesions
RF ablation of painful paraspinal metastatic lesions is also
possible. Extreme caution must be used when metastatic
lesions have destroyed the vertebral body with resultant
loss of the insulative effect of the adjacent bone [51].
Figure 11A shows a CT scan of a large metastatic colorectal
carcinoma lesion involving a rib, vertebral body and
pleural surface. So that thermal damage to the spinal cord
could be avoided, a passive thermocouple was placed along
the lateral aspect of the destroyed pedicle (Fig. 11B,C).
Subsequently, the lesion was treated with three electrode
deployments along the involved rib. With the electrode
deployed in the nearest paraspinal location (Fig. 8D),
treatment was discontinued when the passive thermocouple
reached 40°C. This patient reported a reduction in pain
from 10/10 prior to the treatment to 3/10 4 weeks after the
RF ablation procedure.
Pain assessment and follow-up
Patients’ pain was the primary endpoint in the clinical trial
and was measured with the BPI. All patients were inter-
viewed with the BPI just prior to the procedure, the day
following the treatment, weekly for 1 month, and then
every 2 weeks for the second month through the six-month
follow-up. Each patient was asked to answer the questions
with respect to the lesion that was treated.
The type of malignancy, size, and location of the lesions
that were treated are summarized in Table 1. The majority
of lesions treated were renal and colorectal metastases,
with breast and lung also commonly treated. The most
common sites of tumor involvement were in the pelvis,
sacrum, ribs, and vertebrae. Treated lesions were osteo-
lytic, with the exception of those of two patients who had
mixed osteolytic/osteoblastic lesions. The size of the
treated lesion ranged from 1 cm in a rib to approximately
18 cm in the paraspinal region. The median number of
ablations per lesion was 3.0 (range 1–14) with an average
time per ablation of 11.7 min (range 1.1–52.5 min). The
mean total ablation time was 42.2 min (range 8.0–
218.9 min).
Pain response to RF ablation
A total of 59/62 patients (95%) experienced a drop in pain
that was considered clinically significant when a pre-
defined validated endpoint (≥2 point drop in worst pain in a
24 h period) was utilized [61]. Patients experienced highly
significant reductions in worst pain, average pain, and pain
interference, and significant improvements in pain relief
after RFA of painful metastases involving bone (Fig. 12).
Significant decreases were seen, beginning at week 1 and
extending to week 24 for all pain parameters (Table 2).
Prior to RFA treatment, the mean score for worst pain in a
24 h period was 7.7/10, with a range of 4–10/10. Four, 12,
and 24 weeks after treatment, mean worst pain had
decreased to 4.9, 3.5, and 2.4, respectively. These changes
in worst pain over a 24 h period equate to 36%, 55%, and
69% decreases at weeks 4, 12, and 24, respectively.
Average pain prior to treatment was 5.6, which decreased
to 3.2 at 4 weeks, 2.4 at 12 weeks, and 1.8 at 24 weeks.
These changes in average pain over a 24 h period equate to
43%, 57%, and 68% decreases at weeks 4, 12, and 24
weeks, respectively. Mean pain interference decreased
from 6.6 at baseline to 4.1 at week 4, 3.2 at week 12, and
1.3 at week 24. These changes in mean pain interference
over a 24 h period equate to 38%, 52%, and 80% decreases
at weeks 4, 12, and 24 weeks, respectively. Pain relief from
Table 1 Characteristics of patients treated with RFA in a
multicenter trial
Characteristic
Number of patients 62
Female 22 35%
Male 40 65%
Age Median
64 years
Range
28–88 years
Tumor type (number)
Renal CA 14
Colorectal CA 12
Lung CA 4
Breast 4
Sarcoma 3
Other 25
Tumor size (largest diameter) 6.3 cm Range
1.0–18.0 cm
Tumor location
Pelvis 19
Sacrum 12
Rib 6
Vertebrae 4
Other 21
Prior radiation to treated site 44 71%
Concurrent opioid analgesics 52 84%
11
treatments or medication improved from 50% (0– 100%) at
baseline to 71% at 4 weeks, 79% at 12 weeks, and 90% at
24 weeks. Two patients, whose pain responded to initial
RFA, required retreatment after a recurrence of pain (≥4/10
worst pain) at week 8 and week 16, respectively. Both
patients had significant drops in worst pain (≥4 point drop)
following retreatment.
Opioid use was recorded for each patient and converted
into morphine equivalents using standardized conversions
[61]. Following RFA, opioid requirements peaked at
week 1 (Table 2). At week 4, although opioid requirements
were not statistically different from baseline, a trend
towards decreasing requirements was seen. By weeks 8 and
12, significant reductions in opioid usage were seen.
Increases in opioid usage were seen at week 24, although
the corresponding pain scores did not increase at that time.
These increases in analgesic requirements likely reflect
pain resulting from other sites, as pain scores that were
Average pain
01234 8612162024
0
2
4
6
8
10
Week 10 14 18 22
62 60 57 56 57 4250 34 30 21 17N= 13171825
Pain interference
8612162024
0
2
4
6
8
10
Week 10 14 18 22
62 60 57 56 57 4250 34 31 21 15N= 13171925
01234 8612162024Week 10 14 18 22
0
20
40
60
80
100
Pain relief (%
)
60 60 57 56 56 3847 30 28 19 15N= 12171723
A
A
C
C
B
B
D
D
Worst pain
01234
01234
8612162024
0
2
4
6
8
10
Week
62 60 58 57 57 4250 34 30 21 16N=
10 14 18 22
12161825
Fig. 12 Mean BPI pain scores over time for patients treated with
RFA. A Worst pain; B) average pain; C interference of pain in daily
activities; D pain relief from RFA and medications. Error bars
represent the 95% confidence intervals. N number of patients
completing BPI at each time point
Table 2 Number of patients, BPI mean pain scores, and opioid requirements at baseline and following RFA
Parameter Baseline Day 1 Week 1 Week 4 Week 8 Week 12 Week 24
Number 62 47
a
60 57 42 34 17
Worst pain 7.7 7.0 5.8 4.9 4.1 3.5 2.4
(0–10) P=0.1330 P<0.0001 P<0.0001 P<0.0001 P<0.0001 P=0.0001
Average pain 5.6 4.3 3.9 3.2 2.8 2.4 1.8
(0–10) P<0.0001 P<0.0001 P<0.0001 P<0.0001 P<0.0001 P=0.0001
Pain interference 6.6 5.5 5.0 4.1 3.9 3.2 1.3
(0–10) P=0.0053 P=0.0001 P<0.0001 P<0.0001 P<0.0001 P=0.0013
Pain relief 50 68 67 71 70 79 90
(0–100) P=0.0004 P<0.0001 P<0.0001 P=0.0002 P<0.0001 P=0.0011
Morphine equivalent dose 66.0 220.0 90.8 84.0 27.5 98.4 44.0
(MED) P=0.05 P=0.01 P=0.02 P=0.27 P=0.74 P=0.62
P values are signed-rank tests of the null hypothesis that the difference in the current time period minus the baseline value is equal to zero
a
US cohort only
12
collected with the BPI were specific to the site that was
treated by RFA. Most patients that were included in this
study had progression of their metastatic disease over the
follow-up period.
Significant adverse events following the procedure were
noted in 4/62 (6.5%) patients. One patient developed an
acetabular fracture 6 weeks following RFA of a breast
cancer metastasis, with significant involvement of the
ilium, ischium and acetabulum. The patient required open
reduction and fixation of the acetabulum. In the absence of
RFA, this fracture would have likely occurred. It is not
known whether RFA treatment of this lesion shortened or
lengthened the time to fracture. Three patients developed
worsening of tumor–cutaneous fistulas within 1–2 weeks of
the procedure. These patients had in common a central
necrotic metastatic colorectal lesion in the presacral space
abutting the sacrum. They all had received prior radiation
therapy. The site of the fistula was not along the probe
placement tract in any of the affected patients. Approxi-
mately 20 other patients were treated for metastatic disease
in the low pelvis or perineum and did not develop tumor–
cutaneous fistulas as a result of the treatment. This com-
plication can most likely be avoided by careful examination
of the perineum prior to ablation. If a fistula is present, RFA
of these lesions should not be performed or the patient
should be advised that the treatment may result in ex-
acerbation of the fistula.
A minor adverse event occurred in 1/62 patients (1.6%),
who developed a second-degree skin burn at the ground-
ing-pad site. This burn resolved with conservative therapy.
As a result of this skin burn, all further RF ablations were
monitored with skin temperature thermometers. Cold-
packs were placed over the grounding pads when skin
temperatures exceeded 38°C. One patient developed tran-
sient bowel and bladder incontinence following RFA of a
previously irradiated leiomyosarcoma metastasis involving
the upper sacrum.
Percutaneous RFA is the most studied of the ablative
methods. However, the results of this multicenter trial can
likely be extended to the use of other ablative methods. This
is important, as centers have different experiences and
comfort with the use of other ablative methods. It is im-
portant, also, because the application of these methods for a
particular lesion may favor one of the methods because of
anatomical location or adjacency of other critical structures.
For example, ablation of a lesion adjacent to the spine
requires careful monitoring of the ablation zone during the
procedure. This is more easily achieved by cryoablation in a
CT or MRI suite, or possibly the use of LITT or RF in an
MRI suite, where the ablation margin can be monitored
while the ablation is being performed.
Summary
Percutaneous ablation techniques are important treatment
alternatives for managing pain due to bony metastatic
disease. Significant pain reduction is possible in patients
who have failed to achieve benefit from conventional
therapies that include chemotherapy and external beam
radiation. Importantly, the pain reduction that is achieved is
durable.
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