DISCUSSION
Primary pediatric spinal tumors are rare, however, up to 5% of children
with extra-spinal solid malignancies develop metastasis to the spine
secondary to contiguous invasion or hematogenous spread8. When curative intent is no longer achievable in
patients with spinal malignancies, the main goals of treatment shift
towards preservation of function and improving quality of life via pain
control. Cancer-related pain can pose significant psychological and
physical burden to pediatric patients, resulting in a negative impact on
quality of life 9. Adequate palliative pain management
can be challenging, requiring multimodality treatment strategies to
provide adequate control. This may include oral or intravenous
medications, surgery, radiotherapy (RT) and minimally invasive
procedures such as thermal ablation or cementoplasty10.
Prescribing opioids is a valid initial strategy and is recommended by
the World Health Organisation in their two-step approach for the
treatment of severe cancer-related pain in children10,11. However, opioids have a well-established side
effect profile including constipation, drowsiness, pruritis and nausea12. In addition, opioids pose other risks, such as
tolerance, withdrawal, and dependence syndrome. For patients with pain
refractory to optimized opioid dose escalation and despite other
adjuvant medications (e.g., gabapentin or amitriptyline), alternatives
become limited.
Continuous intravenous infusions of lidocaine or ketamine have been used
to treat pain that is refractory to opioids 13,14.
Lidocaine infusion, unfortunately, requires admission to the intensive
care unit for continuous monitoring during drug initiation and dose
titration due to risks of bradycardia, respiratory depression and
seizure 13. Courade et al . recently published a
prospective multicentric trial to evaluate the efficacy of continuous
infusion of low-dose ketamine through the course of three days as
adjunctive therapy in 38 children and adolescents with persistent pain14. Most of the patients in this study were being
treated palliatively for solid malignancies and 97% of them were
already receiving intravenous morphine for pain management. The
continuous infusion of ketamine significantly reduced the visual analog
scale of pain (VAS) in 50% of the studied population. However,
opioid-sparing effect was only achieved in four of the 38 patients. More
worrisome, 23% of the enrolled patients experienced poor tolerance to
the trialed treatment. Even though these studies included patients with
different tumor histologic types, they show that even non-invasive
therapies may have complications and limitations. The potential
advantages of vertebroplasty over infusion therapy might include
shortened hospital stay after the procedure, elimination of the need for
intensive care monitoring, the procedure being well tolerated even in
young children, and the reduction in dose or elimination of the need for
opioids following the intervention. Nevertheless, comparative
prospective trials are needed to confirm these benefits.
Surgery for patients with advanced spinal tumors usually does not have a
curative intent 15. The most common surgical
techniques in this population include laminectomy for spinal cord
decompression, resection of metastatic intraspinal tumors to prevent
neurological compromise, or removal of epidural disease to allow
radiotherapy. Surgery frequently requires posterior stabilization with
instrumentation to prevent instability 16. Overall,
invasive spine surgery in children poses a significant morbidity with
reported complication rates at 19-21% and include spinal cord shock and
nerve root damage, with an inpatient mortality rate of 3%16,17. In patients with refractory pain and with poor
oncological prognosis, minimally invasive techniques may provide a more
reasonable option, especially if life expectancy is thought to be short.
In this study, recurrent pain was observed only after disease
progression and few weeks before the patients passing.
RT has an important role in the palliative treatment of pediatric spinal
tumors 18. A survey involving an international
research consortium found that the most common indication for palliative
radiation was pain management (43%), with the spine being the second
most common targeted area (14%) 19. Rao et al.20 described pain relief in 83% of their treated
patients, with 43% able to decrease their daily dose of opioids20. When compared to curative RT, palliative RT is
better tolerated and has fewer side effects, with a grade ≥3 toxicity
occurring in only 4% of patients 20,21.
Nonetheless, palliative RT still represents a small percentage of the
indications in children when compared to the adult population19. Part of this may be explained by the fact that
fewer investigations have been published in the pediatric literature and
most practices are translated from the adults guidelines22. Another potential factor limiting the use of
palliative RT in children may be the logistics involved in treatment.
Younger patients may require anesthesia for adequate immobilization, and
parents may face economic challenges involving travel costs and time
away from work 19,23. These can be problematic since
palliative RT regimens frequently require multiple sessions21. It is also important to note that, as the median
survival after palliative RT is 3.6 months, a patient having to
repeatedly come to hospital for RT may not be ideal20. Vertebroplasty has the advantage of being able to
be performed in a single setting, thereby decreasing the number of
hospital visits and potential costs involved. Future cost-analysis
studies are necessary to confirm this hypothesis.
Percutaneous vertebroplasty is a minimally invasive image-guided
procedure that injects PMMA cement within a collapsed vertebral body, to
provide pain relief and mechanical stabilization. The cement
polymerisation generates an exothermic reaction, destroying tumor and
bone nerve endings within a 3 mm margin of the cement7. Additionally, the cement consolidates and
stabilizes fractured fragments and prevents further vertebral body
collapse 7. Vertebroplasty is recommended by several
adult medical societies for the palliative treatment of painful
oncologic fractures or weakened vertebral bodies secondary to neoplasms,
with a reported clinical success of 92% and major complication rate
< 1% 24–29. Vertebroplasty can be
performed under conscious sedation or general anesthesia and takes
approximately 15-30 minutes, with an increment of 5-15 minutes for any
additional vertebral level treated 7.
Vertebroplasty is associated with significant pain reduction and
increase in the level of function, with sustained long-term benefit. A
recently published systematic review included 1445 adults with spinal
malignancies that underwent palliative vertebroplasty alone for the
treatment of painful pathologic fractures 30. Baseline
weighted average Oswestry Disability Index (ODI) was 74.7, with a Visual
Analog Scale (VAS) of 7.5. Both scores significantly decreased following
intervention and demonstrated sustained long-term benefit, with ODI of
28.9 and VAS of 3.0 after 1-year follow-up 30. This
publication also confirmed the safety profile of the procedure, with a
very low incidence of symptomatic complications (1.4%), which included
radiating pain, transient chest pain, radiculopathy without palsy,
hemothorax, hematoma, radicular neuritis, asymptomatic and symptomatic
pulmonary embolisms, bilateral leg motor deficits, cauda equina, and
complete paraplegia. Pain might increase immediately after the procedure
and is likely related to muscular spasm, and the full pain relief
benefit following intervention may take up to two weeks. Cement leak can
occur but the vast majority are asymptomatic and usually of no clinical
significance 30. Since these studies were performed in
adults, the true benefit and complication risks in the pediatric
population still needs further investigation.
All three patients treated with vertebroplasty in this retrospective
study described significant pain improvement, with Patient 1 and 2 no
longer requiring oral medications. Few cases of vertebral augmentation
for pain control have been reported in pediatric patients and are
summarized in Table 2 31–35. Patients were treated
with kyphoplasty and vertebroplasty in four of the five case reports and
only two of the eight patients that were treated had an underlying
malignancy 33,34. There is no evidence of clinical
superiority of kyphoplasty over vertebroplasty, nor demonstration of
lower incidence of complications 36. Kyphoplasty may
require longer procedural times due to its increased technical
complexity, has higher equipment costs, and typically requires larger
needles for access which theoretically could increase complication risks36.
Vertebroplasty in the pediatric setting could potentially affect the
normal development of the vertebral body due to mechanical restriction
of growth or thermal disruption of the growth plate. Nonetheless, this
has not been observed by other authors after a mean follow-up of 3 years
(ranging from 3 months to 8 years) [34]. In pediatric patients with
spine metastasis, the median survival of those who have the need to
undergo radiation therapy or surgery, or who develop a pathologic
fracture or spinal cord compression, is less than one year37. Therefore, the theoretical concerns of growth
restriction should be weighed against the patient’s symptoms and
potential benefit of the procedure.
Although the patients in the current study had pain secondary to
metastatic disease to the spine, vertebroplasty could be useful in
managing pain in other pediatric oncological scenarios. For instance, in
patients with acute lymphoblastic leukemia (ALL) since up to 16% may
have vertebral fractures at the time of diagnosis 38.
Additionally, vertebroplasty could be a useful treatment in patients who
develop painful vertebral fractures due to treatment-induced
osteoporosis 39. Since these indications were not
assessed on the current study, further investigation is required.
This study has several limitations. First, it is retrospective and did
not allow for homogeneous assessment of patient reported outcomes or
quality of life measures to capture the overall impact of the
intervention. Second, the number of patients included is very small. In
addition, all three patients had metastatic disease to the spine rather
than a primary bone-based malignancy, and the application of this
intervention in patients with primary spine tumors is still unknown.
Patient 1 received neoadjuvant chemotherapy at the time of
vertebroplasty, and Patients 2 and 3 had received recent palliative
radiation prior to the procedure. This may confound the reported
improved pain post vertebroplasty and make it challenging to truly
quantify the overall impact of the intervention. However, in all three
cases where vertebroplasty was performed, there was significant
reduction in pain and medication use, and there was evidence of
sustained tumor and pain response in two cases. This improvement would
be consistent with published data in the adult literature.
In conclusion, vertebroplasty in children with spinal bony metastases
may provide improved pain control with attendant reduction in the need
for pain medications. This procedure could provide an additional option
to accompany medical or radiation therapies for pain control in the
palliative context and increased awareness of this treatment option
could improve the quality of life for children and adolescents with
vertebral tumors.
Conflict of Interest StatementThe authors have nothing to disclose.