1. Review article
Percutaneous image-guided cryoablation of spinal metastases: A
systematic review
Navraj S. Sagoo a,⇑
, Ali S. Haider b
, Ahmad Ozair c
, Christopher Vannabouathong a
, Masum Rahman d
,
Maryam Haider e
, Neha Sharma f
, Karuna M. Raj g
, Sean D. Raj h
, Justin C. Paul i
, Michael P. Steinmetz j
,
Owoicho Adogwa k
, Salah G. Aoun k
, Peter G. Passias l
, Shaleen Vira a
a
Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, United States
b
Texas A&M University College of Medicine, Bryan, TX, United States
c
King George’s Medical University, Lucknow, Uttar Pradesh, India
d
Department of Neurosurgery, Mayo Clinic, Rochester, MN, United States
e
John Peter Smith Hospital, Fort Worth, TX, United States
f
Roseman University of Health Sciences, South Jordan, UT, United States
g
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States
h
Department of Radiology, Baylor University Medical Center, Dallas, TX, United States
i
OrthoConnecticut Orthopedics, Danbury, CT, United States
j
Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH, United States
k
Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX, United States
l
Department of Orthopaedic Surgery, NYU Langone Orthopedic Hospital, New York, NY, United States
a r t i c l e i n f o
Article history:
Received 17 August 2021
Accepted 11 November 2021
Available online xxxx
Keywords:
Cryoablation
Spinal tumor
Spine metastases
a b s t r a c t
Percutaneous cryoablation (PCA) is a minimally invasive technique that has been recently used to treat
spinal metastases with a paucity of data currently available in the literature. A systematic review was
performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines. Prospective or retrospective studies concerning metastatic spinal neoplasms treated
with current generation PCA systems and with available data on safety and clinical outcomes were
included. In the 8 included studies (7 retrospective, 1 prospective), a total of 148 patients (females = 63%)
underwent spinal PCA. Tumors were located in the cervical (3/109 [2.8%], thoracic (74/109 [68.8%], lum-
bar (37/109 [33.9%], and sacrococcygeal (17/109 [15.6%] regions. Overall, 187 metastatic spinal lesions
were treated. Thermo-protective measures (e.g., carbo-/hydro-dissection, thermocouples) were used in
115/187 [61.5%] procedures. For metastatic spinal tumors, the pooled mean difference (MD) in pain
scores from baseline on the 0–10 numeric rating scale was 5.03 (95% confidence interval [CI]: 4.24 to
5.82) at a 1-month follow-up and 4.61 (95% CI: 3.27 to 5.95) at the last reported follow-up (range 24–
40 weeks in 3/4 studies). Local tumor control rates ranged widely from 60% to 100% at varying follow-
ups. Grade I-II complications were reported in 9/148 [6.1%] patients and grade III-V complications were
reported in 3/148 [2.0%]) patients. PCA, as a stand-alone or adjunct modality, may be a viable therapy in
appropriately selected patients with painful spinal metastases who were traditionally managed with
open surgery and/or radiation therapy.
Published by Elsevier Ltd.
1. Introduction
Treatment paradigms for patients with painful spinal metas-
tases have evolved significantly over the past four decades. Con-
ventional management strategies typically employ a combination
of external beam radiation, systemic therapy, and open surgical
techniques [1,2]. However, these measures are often not feasible
in patients with advanced systemic disease and co-morbidities,
leaving these complex patients with limited treatment options.
Percutaneous image-guided ablative techniques have emerged as
less invasive stand-alone or adjunct modalities to combat meta-
static spinal tumors. These novel measures include radiofrequency
ablation (RFA), spinal laser interstitial thermal therapy (sLITT), and
microwave ablation (MWA) [3–5].
https://doi.org/10.1016/j.jocn.2021.11.008
0967-5868/Published by Elsevier Ltd.
⇑ Corresponding author.
E-mail address: navraj.sagoo@utsouthwestern.edu (N.S. Sagoo).
Journal of Clinical Neuroscience xxx (xxxx) xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience
journal homepage: www.elsevier.com/locate/jocn
Please cite this article as: N.S. Sagoo, A.S. Haider, A. Ozair et al., Percutaneous image-guided cryoablation of spinal metastases: A systematic review, Journal
of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2021.11.008

2. Adding to the armamentarium of minimally invasive treatment
modalities, percutaneous cryoablation (PCA) is a technique that
has been used recently to treat spinal metastases [6]. This tech-
nique involves percutaneous placement of a needle applicator
(i.e., cryoprobe) into a spinal tumor using image guidance. A room
temperature, pressurized gas, most commonly Argon, is used to
rapidly cool the tip of the cryoprobe to temperatures lower than
40 °C, leading to the formation of a hypoattenuating ‘‘ice ball”
which is readily identified by computed tomography (CT) imaging
[7–8]. Active thawing of the ice is then performed by infusing high-
pressure helium through the same system, which sets up an osmo-
tic gradient inducing local tissue necrosis by both cellular and vas-
cular injury. Spinal PCA is a relatively new procedure with a
paucity of data on its usage currently available in the literature.
In comparison to established treatments (e.g., radiotherapy) which
often lead to modest pain and functional outcomes, spinal PCA is
gaining interest as a palliative treatment due to its rapid analgesic
effects and its ability to expedite resumption of systemic therapy
[9–11].
The primary objective of this systematic review is to assess and
report on the growing body of literature that addresses the use of
PCA in the management of metastatic spinal tumors. The clinical
outcomes and safety of this procedure are reviewed.
2. Methods
A systematic review was performed according to the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines [12]. A literature search was conducted using
the electronic databases PubMed, Cochrane Central Register of
Controlled Trials (CENTRAL), and Scopus from their inception to
July 31, 2021. The keywords and medical subject headings (MeSH)
terms included the following search terms: ‘‘spine AND (cryoabla-
tion OR cryosurgery)”. Identified studies were uploaded into End-
noteÒ
and duplicates were removed.
2.1. Study selection
Pre-specified inclusion and exclusion criteria were defined a
priori. Studies were included if they met the following criteria: 1)
metastatic spinal neoplasms treated with current generation PCA
systems alone or in combination with other treatments, 2) avail-
able data on at least one clinical outcome (i.e., pain relief, local
tumor control, functional outcomes, complications), 3) prospective
or retrospective studies with at least 3 patients, 4) English lan-
guage. Exclusion criteria were defined as follows: 1) PCA of tumors
in anatomical regions besides the spine or sacrum, 2) patients trea-
ted with the antecedent ‘‘open system” technique of cryosurgery
involving surgical curettage with direct pouring of liquid nitrogen
into the tumor cavity, 3) PCA of primary or benign spine tumors, 4)
meta-analyses, 5) reviews or editorials, or 6) animal and experi-
mental laboratory studies.
Two authors (N.S.S. and M.R.) independently screened the titles
and abstracts of all articles based on the pre-specified inclusion
and exclusion criteria. Articles that met the inclusion criteria were
then full-text reviewed independently by the same two authors
and eligible articles were selected based on the set criteria. Dis-
agreements between the two authors were resolved via involve-
ment of a third author (A.S.H.). References of relevant articles
were also reviewed in case any were missed via the electronic
search.
2.2. Data extraction and quality assessment
One author (A.O.) initially extracted the data from the studies.
This data was independently confirmed by two other authors (N.
S.S. and A.S.H.). For each study, the following variables were
extracted: 1) baseline study characteristics which included study
design, sample size, gender, age, spinal levels affected, primary
tumor histology, tumor characteristics (e.g. nidus size, radio-
graphic features [lytic or sclerotic]), 2) pain experienced at various
time points and the pain scales that were utilized to measure it, 3)
PCA-related variables (i.e., concurrent cement augmentation, anes-
thetic protocol, imaging guidance, ancillary thermo-protective
measures), 4) local tumor control which was defined as locally
stable or improved disease on computed tomography (CT) or mag-
netic resonance (MR) imaging at the last imaging follow-up, 5)
procedure-related complications which were classified according
to the Common Terminology Criteria for Adverse Events (CTCAE,
version 5.0). Complications were assessed and classified into major
(CTCAE grade 3 – 5) and minor (CTCAE grade 1 – 2).
Given that all included studies had a non-randomized, cohort
design, the risk of bias assessment was carried out using the New-
castle Ottawa Scale (NOS) [13]. The NOS for cohort studies utilizes
a star-based system for rating the methodological quality of the
study and is comprised of three major domains: selection, compa-
rability, and outcome. Two reviewers (N.S.S. and A.O.) indepen-
dently assessed the quality of each study with disagreements
resolved via involvement of a third author (S.V.) (Supplementary
Table 1). Articles scoring at least five stars were retained in our
analysis.
2.3. Data synthesis
Studies reporting pain changes following PCA of metastatic
spinal tumors were calculated according to a 0- to 10-point
numeric rating scale (NRS). Single-arm meta-analyses were con-
ducted to calculate the pooled mean difference (MD) from baseline
in pain scores at 1-month and at the last recorded follow-ups.
Meta-analyses were conducted in R (R Foundation for Statistical
Computing; Vienna, Austria), using the meta package. The 95% con-
fidence interval (CI) was calculated for each meta-analysis. Hetero-
geneity between studies was assessed using the I2
statistic, where
I2
values greater than 40% indicated statistically significant hetero-
geneity. The results of both the fixed- and random-effects models
were presented in the forest plot. All other outcomes (e.g., demo-
graphics, nidus size, radiographic features, local tumor control,
complications, and procedure-related parameters) were reported
descriptively due to significant heterogeneity across studies and
the limited number of studies reporting these outcomes.
3. Results
The initial literature search yielded 254 articles (PubMed: 92,
Scopus: 161, CENTRAL: 1). Seven additional articles were found
based on review of relevant references. After the removal of dupli-
cates, there were 175 articles. 117 studies were excluded based on
screening of the title and abstract. 58 full-text articles were then
assessed for inclusion. Of these, 50 articles failed to meet inclusion
criteria and were subsequently excluded. Eight non-randomized
studies (seven retrospective and one prospective) were included
in this systematic review (Fig. 1) [8,14–20].
All included studies reported exclusively on metastatic spinal
tumors [8,14–20]. Based on the Newcastle-Ottawa Scale, all studies
were rated to have three stars in the ‘selection’ domain, zero stars
in the ‘comparability’ domain, and three stars in the ‘outcome’
domain (Supplementary Table 1). Loss to follow-up in all studies
N.S. Sagoo, A.S. Haider, A. Ozair et al. Journal of Clinical Neuroscience xxx (xxxx) xxx
2

3. was either absent or minimal. Demographics and baseline charac-
teristics of included studies are summarized in Table 1.
3.1. Patient Demographics and clinical characteristics
In the 8 included studies, a total of 148 patients (55 males and
93 females) underwent spinal PCA. The mean age of patients ran-
ged between 53 and 73.3. Tumors were located in the cervical
(3/109 [2.8%], thoracic (74/109 [68.8%], lumbar (37/109 [33.9%],
and sacrococcygeal (17/109 [15.6%] regions across 7/8 studies with
available data. Overall, 187 metastatic spinal lesions were treated.
Breast was the most common primary tumor origin for metastatic
tumors (32/187[(17.1%%]), followed by lung (23/187 [(12.3%]) and
thyroid (19/187 [(10.2%]). Three studies reported the radiographic
appearance of 131 (131/187 [(70.1%]) lesions [8,14,16]: 90/131
[(68.7%] were osteolytic, 30/131 [(22.9%] were sclerotic, and
11/131 [(8.4%] were both lytic and sclerotic. Mean lesion diameters
ranged between 2.09 mm and 35.5 mm. Six studies reported on the
anatomical location of 160/187 [(85.6%] lesions [8,14–18]: 108/160
[(67.5%] lesions were located exclusively in the vertebral body,
27/160 [(16.9%] lesions were located exclusively in the posterior
elements, and 16/160 [(10.0%] lesions involved both. 35/156
[(22.4%] lesions invaded the epidural space across seven studies
with available data.
3.2. Procedure-related parameters
Image guidance for PCA procedures exclusively involved com-
puted tomography (CT) in seven studies [8,14–17,19–20]; a combi-
nation of CT and C-arm fluoroscopy was used in two studies
[14,18]; Cone beam CT was used to guide PCA in two studies
[14,16]. With regards to anesthetic protocol, general anesthesia
was used in 69/148 [(46.6%] patients. Conscious sedation and local
anesthetic were used in 79/148 [(53.4%] patients. In addition to
PCA, four studies employed the use of vertebral consolidation by
percutaneous vertebroplasty in 70/187 [(37.4%] lesions, in the
same interventional session (45/70 [(64.3%] lesions) or up to two
weeks postoperatively (25/70 [(35.7%] lesions). Ancillary protec-
tive measures to prevent thermal-mediated injuries to the spinal
cord and nerve roots (e.g., carbo-/hydrodissection, thermocouples,
somatosensory evoked potentials) were used in 115/187 [61.5%]
procedures (Table 2).
Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Flow Diagram.
N.S. Sagoo, A.S. Haider, A. Ozair et al. Journal of Clinical Neuroscience xxx (xxxx) xxx
3

4. 3.3. Pain outcomes
In order to assess the efficacy of PCA as a palliative intervention,
pain scales were utilized in six of the eight studies. In the studies
reporting on metastatic spinal tumors, a 1-month meta-analysis
of the MD in pain scores following PCA demonstrated statistically
significant heterogeneity (I2
= 90%, p < 0.01). In the random-
effects model, the pooled MD in pain scores from baseline on the
0–10 NRS was 5.03 (95% CI: 4.24 to 5.82). A similar meta-analysis
at the last reported follow-up (range 24–40 weeks in three studies;
60 weeks in one study) demonstrated statistically significant
heterogeneity across studies (I2
= 95%, p < 0.01). In the random-
effects model, the pooled MD in pain scores from baseline was
4.61 (95% CI: 3.27 to 5.95) (Fig. 2).
3.4. Local tumor control
Six studies assessed the ability of PCA to achieve local tumor
control (i.e., no evidence [stable or improved] of local tumor pro-
gression based on imaging at last follow-up), accounting for
108/187 [57.8%] lesions. At a 7- to 12-month follow-up, 4/6 studies
reported local control (LC) rates ranging from 60% to 100%
[8,16,17,19]. Autrusseau et al. [14] reported stable or improved dis-
ease in 6/10 [60%] metastatic lesions (median 25-month follow-
up). Gravel et al. [15] reported an LC rate of 100% at a 2-week
follow-up.
3.5. Complications
Overall, complications were reported in 12 patients (12/148
[8.1%]) across the included studies. Specifically, three patients
(3/148 [2.0%]) had major complications which included, in one
patient each, postoperative persistent paraparesis, intraoperative
cardiac arrhythmia requiring a pacemaker, and periprocedural
takotsobu cardiomyopathy in a patient with metastatic paragan-
glioma. Nine patients (9/148 [6.1%]) had minor complications of
which the most common event was transient nerve root radicu-
lopathy of a lower extremity. Complications are further listed in
detail in Table 3.
4. Discussion
In the 1960s, the field of cryosurgery involved open surgical
curettage with direct application of liquid nitrogen into the tumor
cavity [21]. Subsequent technological advancements have led to
the emergence of image-guided percutaneous placement of cry-
oprobes allowing for room temperature, pressurized argon and
helium gases to be transmitted through a sealed, segmentally insu-
lated probe, thereby inducing localized tissue freezing and thaw-
Table 1
Demographics and Clinical Characteristics.
Author
& Year
Study
Design
No. of
patients
treated
with
spinal PCA
No. of
Lesions
Treated
with
PCA
M, F Mean
age at
ablation
(SD)
Spinal
level
affected
Anatomic
Location
within spine
(number of
lesions)
No. of
lesions
with
Epidural
Extension
Radiographic
Characteristics
Type of
Tumor
Primary Histology
[19] P 14 14 6,8 54.5
(14.37)
1C/10 T
/1L/2S
n/s 7 lesions
with
epidural
extension
n/s Metastases 4 Lung, 3 RCC, 3 breast, 1
rectal, 1 tongue, 1 thyroid, 1
melanoma
[8] R 14 31 5,9 53
(range
20–73)
1C/8 T/
14L/6S/
2Cx
12 Vertebral
body
5 Pedicle
4 Lamina
1 Spinous
process
n/s 9 sclerotic; 22
lytic
Metastases 4 lung, 3 CRC, 2 breast, 2
thyroid, 1 HNSCC, 1
pancreatic adenocarcinoma,
1 hemangioendothelioma
[20] R 11 13 5,6 53
(range
52–81)
0C/2 T/
3L/7S
n/s 2 lesions
with
epidural
extension
n/s Metastases 4 breast, 2 HCC, 1 RCC, 1
bladder, 2 ovarian, 1
prostate
[18] R 23 23 3,20 73.3
(4.1)
0C/
17 T/
6L/0S
23 Vertebral
body
0 lesions
epidural
extension
n/s Metastases n/s
[16] R 39 54 15,24 Range
24–75
n/s 49 Vertebral
body
5 Pedicle and
Vertebral
body
4 lesions
with
epidural
extension
12 Sclerotic,
42 lytic
Metastases 16 thyroid, 7 breast, 5 lung,
3 paraganglioma/
phaeochromocytoma, 8
misc.
[14] R 41 46 19,22 59.7
(4.4)
0C/
33 T/12
L/0S
19 Vertebral
body
16 posterior
arch
11 Both
22 lesions
with
epidural
extension
26 Lytic, 9
Sclerotic, 11
Mixed
Metastases 16 breast, 9 lung, 5 renal
[17] R 3 3 1,2 55.7 1C/2 T 1 posterior
elements
2 Vertebral
body
0 lesions
with
epidural
extension
n/s Metastases 1 lung, 1 adenoid cystic
carcinoma, 1uterus
[15] R 3 3 1,2 61.7 2 T/1L 3 Vertebral
body
0 lesions
with
epidural
extension
n/s Metastases n/s
No. – number; P - prospective; R - retrospective; PCA - Percutaneous Cryoablation; M - male; F - female; C - cervical; T - thoracic; L -lumbar; S - sacrum; Cx - coccyx; RCC -
renal cell carcinoma; CRC - colorectal cancer; HNSCC - head and neck squamous cell carcinoma; HCC - hepatocellular carcinoma; DLBCL - diffuse large B-cell lymphoma; OO-
osteoid osteoma; OB-osteoblastoma; n/s - not specified.
N.S. Sagoo, A.S. Haider, A. Ozair et al. Journal of Clinical Neuroscience xxx (xxxx) xxx
4

5. ing, respectively. Considering the novelty of its use in the spine,
only eight non-randomized studies were included for a final anal-
ysis in our review. This is reflective of the paucity of literature and
the low diffusion of PCA as a palliative and curative technique for
spinal metastases.
In our findings, there was a significant improvement in pain
across all meta-analyzed studies at both a 1-month and last
recorded follow-ups, demonstrating the effective analgesic proper-
ties of this modality in metastatic spinal tumors at the short- to
mid-term period. Similar short-term improvements in pain out-
comes have been observed in other systematic reviews examining
both RFA and MWA of spinal metastases, respectively [4,5]. Gen-
naro et al. [22] compared the efficacy of RFA, MWA, PCA, and mag-
netic resonance (MR)-guided focused ultrasound in reducing pain
from metastatic bone disease, with all techniques achieving pain
relief after 1 and 3 months, in up to 91% and 95% of patients,
respectively. Although the actual mechanism of pain relief from
these ablation modalities remains elusive, the significant palliative
effects observed are likely due, in part, to the resultant reduction in
tumor burden following application of heat- or cold-based modal-
ities. In PCA specifically, short-term pain relief may additionally be
related to the cooling mechanism of cryoablation which provides
Table 2
Procedure-related Variables.
Author
& Year
Imaging Guidance Anesthesia
Protocol
(number of
patients)
Nidus size,
diameter (mm)
LC rates Imaging
Follow-up
Number of lesions
treated with Cement
Augmentation
Ancillary Protective Measures
[19] CT GA (14) n/s 5/7 lesions with
epidural
extension (71.4%)
Mean
7.1 months
0 lesions n/s
[8] CT Conscious
sedation and LA
(13); GA (1)
n/s 30/31 lesions
(96.8%)
Median
10 months
2 lesions treated
during same
interventional session
Carbodissection or
hydrodissection + thermocouple
in all procedures
Intraprocedural motor-evoked
potential monitoring in 1
procedure
Cutaneous application of warm
saline solution in all procedures
[20] CT LA (11) Mean 2.09
(SD = 0.54)
n/s Median
7.4 months
0 lesions n/s
[18] CT/fluoroscopy LA (23) n/s n/s 6 months 23 lesions treated
during same
procedure
n/s
[16] CT or Cone Beam CT Conscious
sedation and LA
(29); GA (10)
Mean 18.4 mm
(range 6–
38 mm)
32/54 lesions
(59.3%)
1 year 25 lesions treated at
median 15 days
postoperatively
Carbodissection 35 procedures
(64.8%)
[14] CT/fluoroscopy
(62%);
CT guidance (34%);
Cone-beam CT
guidance (4%)
GA (41) Mean 35.5 mm
(SD = 15.4 mm)
6/10 (60%) lesions Median
25 month
20 lesions treated
during same
interventional session
Hydrodissection (28 procedures)
Carbodissection (12 procedures)
Thermocouple (36 procedures)
Somatosensory evoked
potentials (1 procedure)
[17] CT GA (3) Mean 25 mm 3/3 metastatic
lesions (100%)
Mean
7.5 months
0 lesions n/s
[15] CT Conscious
sedation (3)
Mean 21 mm 3/3 (100%) 2 weeks 0 lesions Carbodissection (3 procedures)
CT – computed tomography; SD - standard deviation; LC – local tumor control; mm - millimeter; n/s - not specified; min - minute; GA - general anesthesia; LA - local
anesthesia
Fig. 2. Forest plots demonstrating pooled reduction in pain scores across studies reporting on percutaneous cryoablation of metastatic spine tumors at the 1-month and final
reported follow-ups.
N.S. Sagoo, A.S. Haider, A. Ozair et al. Journal of Clinical Neuroscience xxx (xxxx) xxx
5

6. an anesthetic effect on treated tissues and nerves [2,8]. In addition,
when compared to heat-based techniques (e.g., RFA, sLITT), PCA
may also offer rapid analgesia due to its lower propensity to induce
post-ablation edema and pain rebound in the early postoperative
period [19,23]. Furthermore, no studies have yet directly compared
the analgesic efficacy of PCA to more established treatments such
as conventional radiation therapy. However, based on the current
evidence, it is recommended to use PCA as an additional therapeu-
tic option in combination with more established treatments (e.g.,
radiotherapy), with the final goal of improving pain relief and local
tumor control.
Several patients (35%) across the included studies also under-
went cement augmentation in the same interventional session or
within two weeks postoperatively; Cement augmentation is often
necessary for stabilization and/or pain palliation as cryoablation
itself may induce collateral damage to adjacent trabeculated bone,
leading to compression fractures and pain [18]. With this in mind,
it would be challenging, with the current dataset, to differentiate
whether the improvement in pain in these particular patients
was due to PCA alone or due to cement augmentation, or a syner-
gistic effect of combined therapies. Higher quality studies with
longer follow-ups are warranted to investigate the long-term
effects of PCA on analgesia in metastatic spinal tumors, though this
may be difficult considering the typically shorter life expectancies
and comorbidities of the target population.
Local tumor control was investigated across most studies in this
analysis, and high rates of success (60–100%) were seen at widely
varying follow-ups. Variation in tumor control is possibly attribu-
ted to patients presenting at varying time points in their disease
course, thus leading to some discrepancies in response to treat-
ment. Heterogeneity in tissue properties due to differing primary
histology may have also played a role in responsiveness to PCA.
Importantly, most spinal lesions in the present analysis were
located within the vertebral body as opposed to the posterior ele-
ments, with only a limited number of tumors exhibiting epidural
extension; As such, LC rates in patients with epidural tumor exten-
sion remains to be fully understood. Moses et al. [19] assessed LC
rates exclusively in lesions with epidural extension; in this study,
71.4% of lesions were reported to be stable or improved at the last
imaging follow-up (mean 7.1-month); However, only seven
tumors with epidural extension were analyzed in this series with
no comparative group. Gravel et al. [16] found a LC rate of 59.3%
in 54 metastases at a follow-up of one year; however, for metas-
tases measuring<25 mm and at least 2 mm or more away from
the spinal canal, the LC rate was 95.8%. Thus, although these results
are encouraging, a curative role for PCA can only be suggested
emphasizing the need for large prospective studies to corroborate
these results and analyze the efficacy of PCA as a method of treat-
ing tumors with epidural extension and compression of the thecal
sac. Furthermore, a comprehensive and standardized follow-up
interval regimen for imaging should be established which would
allow for direct comparisons of outcomes within the literature.
In our review, patients generally tolerated PCA well, with an
overall incidence of 8.1%. In comparison, complications following
sLITT and RFA of spinal metastases have been reported as 18.3%
and 16%, respectively [3,4]. The slight discrepancy in complications
between different ablative modalities is multifactorial. The rela-
tively higher prevalence of tumors treated exclusively in the verte-
bral body in our analysis understandably led to lesser
complications due to the safer distance from critical neurovascular
structures. In addition, the observed lower complication incidence
may also be partially attributed to the fact that freeze-induced cel-
lular injury related to PCA may be less destructive to some neu-
rovascular structures as compared to other heat-based ablative
modalities [7]. Thermal protective measures were additionally
implemented in conjunction with PCA in the majority (62%) of
patients in our review. These measures included epidural or neuro-
foraminal injection of sterile carbon dioxide or warmed 5% dex-
trose water to displace the spinal cord or foraminal nerve root,
cutaneous protection by surface application of warm saline, or
intraprocedural motor-evoked potential monitoring. Collectively,
these ancillary protective procedures are particularly important
in lesions with close proximity to the spinal canal. Understandably,
to prevent neurological complications and enhance the likelihood
of complete tumoral ablation, such nerve-protective methods
should be implemented in PCA cases. Despite the low percentage
of complications seen in our review, careful selection of candidates
as well as intermittent monitoring of the ablative zone is necessary
to avoid injury of adjacent neurovascular structures.
This study has several important limitations, particularly
related to the fact that there were few, non-randomized single-
arm studies that were available for inclusion. In addition to major
heterogeneity across the eight included articles, the aggregate
patient cohort remained small overall and the majority of studies
reported varied and short-term follow ups. This places emphasis
on standardization of reported follow-up to allow comparisons
between modalities across the literature. Many patients undergo-
ing PCA also had advanced systemic disease and co-morbidities
which may potentially confound treatment outcomes. Definitive
conclusions about local tumor control are difficult to make due
to a paucity of assessment data and minimal follow-up. With this
in mind, randomized controlled studies at multiple institutions
are needed to compare open surgery, radiation therapy, and other
ablative modalities to PCA to determine the relative impact of PCA
as a standardized means of reducing tumor burden and inducing
effective pain palliation.
5. Conclusion
PCA, as a stand-alone or adjunct modality, may be a viable ther-
apy in appropriately selected patients with painful spinal metas-
Table 3
Complications
Post-Ablation Complications
Author
& Year
Major Complications (CTCAE
Grade 3 – 5)
Minor Complications (CTCAE
Grade 1 – 2)
[19] 0 0
[8] 0 2 post-procedure radicular LE
nerve pain successfully treated
with transforaminal nerve root
block
[20] 0 2 transient unilateral LE
radiculopathy and weakness
[18] 0 0
[16] 1 post-procedure persistent
paraparesis
1 periprocedural Takotsubo
cardiomyopathy in patient
with metastatic
paraganglioma
1 transient nerve root
radiculopathy with persistent
dysesthesia
1 transient nerve root
radiculopathy
[17] 0 0
[14] 1 intraoperative cardiac
arrhythmia requiring
pacemaker
1 distended bladder requiring
catheterization
1 post-ablation pain requiring
analgesics
1 brachial plexus injury secondary
to positioning patient in the
supine position during PCA with
spontaneous resolution at
3 months
[15] 0 0
CTCAE - Common Terminology Criteria for Adverse Events; PCA - percutaneous
cryoablation; LE - lower extremity.
N.S. Sagoo, A.S. Haider, A. Ozair et al. Journal of Clinical Neuroscience xxx (xxxx) xxx
6

7. tases who were traditionally managed with open surgery and/or
radiation therapy. Our review showed that PCA is effective in
achieving pain relief in the short- to mid-term period. In addition,
findings of sustained local tumor control and minimal major and
minor complications were noted. However, larger prospective
studies with longer follow-ups investigating the palliative and
curative roles of spinal PCA are warranted.
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.jocn.2021.11.008.
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