Treatment Strategies
Supportive care
Pain frequently is resistant to standard analgesics. Pain control with opioids as clinically indicated
Steroids to lessen pain, reduce vasogenic cord edema, and avoid radiation-induced spinal edema
Dexamethasone 96 mg; administer intravenously over 15–30 min, followed by:
Dexamethasone 24 mg/dose; administer orally for 4 doses per day (approximately every 6 hours) for 3 days. Gradually decrease doses and increase administration intervals (taper) to discontinue use after 10 days
Note: This regimen was used in a randomized controlled trial in which high-dose dexamethasone was compared to no therapy in 57 patients with metastatic SCC treated with RT alone. Eighty-one percent of the participants in the intervention arm were ambulatory after treatment compared with 63% in the control group. Significant side effects were reported in 11% of those who received high-dose dexamethasone
Sørensen PS et al. Eur J Cancer 1994;30A:22–27
or
Dexamethasone 10 mg; administer as a short intravenous infusion over 10–20 minutes, followed 6 hours later by:
Dexamethasone 4 mg; administer orally every 6 hours. Taper to discontinue use within 2 weeks
Note: Used because of an increased incidence in side effects observed with higher doses
Heimdal K et al. J Neurooncol 1992;12:141–144
Vecht CJ et al. Neurology 1989;39:1255–1257
Radiation therapy
Preferred treatment for most patients with metastatic SCC
If surgery is contraindicated, external beam radiotherapy with corticosteroids remains first-line therapy
Indications for postoperative radiation are not clear: Treatment of tumor relapses versus combining radiotherapy with surgery to improve local control (Lutz et al. 2011); however, RT may increase the risk of pathologic fracture in cases of spinal instability
Important variables:
(1) Early diagnosis
(2) Favorable histology
A prospective analysis of 209 patients treated with radiation and steroids
Among patients who were ambulatory, nonambulatory, or paraplegic before treatment, 98%, 60%, and 11%, respectively, were able to ambulate
Early diagnosis was the most important predictor of success, so a majority of patients able to walk and with good bladder function maintained these capacities
When diagnosis was late, tumors with favorable histologies (ie, multiple myeloma, and breast and prostate carcinomas) responded best to radiation therapy
Duration of response was also influenced by histology. A favorable histology was associated with high median response durations: for multiple myeloma, and breast and prostate carcinomas, 16, 12, and 10 months, respectively
Median survival time was 6 months, with a 28% probability of survival at 1 year
There was a correlation between patient survival and duration of response, with systemic relapse of disease generally being the cause of death
Notes:
Transient myelopathy can develop 2–6 months after radiation therapy secondary to transient demyelination of the posterior columns
The symptoms of transient myelopathy often resolve spontaneously within a year in most cases
Chronic progressive myelitis is a late delayed complication of radiation
Conventional radiation:
Efficacy of conventional radiotherapy is well established with complete or partial responses observed in 65–86% of patients
There is no difference in efficacy and tolerance between different radiation schema but a short schema (8 Gy in 1 fraction) may be preferred in patients with long bone metastases or an estimated life expectancy ≤3 months
Stereotactic radiosurgery (also called stereotactic body radiation therapy [SBRT])
A growing body of literature supports its efficacy in treating spine lesions
Used to deliver a high dose of RT to the target volume while protecting organs at risk, usually with a single fraction
Advocates claim it can partially overcome intrinsic tumor resistance to ionizing radiation, but solid data supporting the strategy is not available
May be applied to any part of the body with stereotactic techniques such as Volumetric-Modulated Arc Therapy (VMAT) or CyberKnife
For a single lesion, 8–24 Gy may be given depending on the distance to the spinal cord
More protracted regimens can deliver 20–30 Gy in 2–6 fractions
The best candidates include: (a) solitary lesion or oligometastatic disease; (b) ≥5 mm between lesion and spinal cord; (c) good general health status; (d) no spinal cord compression; and (e) life expectancy ≥6 months (Chawla S et al. Bone 2009;45:817–821)
Exclusion criteria: Canal narrowing >25%, instability requiring surgical treatment, and a life expectancy =3 months (Lutz S et al. Int J Radiat Oncol Biol Phys 2011;79:965–976)
May be valuable when considering treatment of a recurrence after RT such as spinal tumors where retreatment is limited by tolerance of the spinal cord
Intensity modulated radiotherapy (IMRT)
Can significantly reduce the incidence and severity of iatrogenic complications by improving radiation conformation around the target volumes, with more accurate dose distributions using intensity modulation of multiple-beam irradiation (Veldeman L et al. Lancet Oncol 2008;9:367–375)
Because IMRT requires precise repositioning devices and correction of setup errors (particularly for spinal or paraspinal lesions), it must be associated with repositioning techniques guided by imaging (IGRT) (Guckenberger M et al. Radiother Oncol 2007;84:56–63)
IMRT can deliver high doses of radiation within a few fractions, mimicking stereotactic radiosurgery
Single-fraction image-guided IMRT may also be used
A retrospective analysis of 62 patients reported fracture progression in 39% of patients treated with IMRT. Risk factors for fracture were: (a) Lesions located between T10 and sacrum; (b) lytic features; and (c) percent involvement of a vertebral body. Local tumor progression occurred in only 7 patients (Rose PS et al. J Clin Oncol 2009;27:5075–5079)
3. Surgery ± Radiation
Surgery should be considered in patients with:
Note:
(Patchell R et al. Proc Am Soc Clin Oncol 2003;22:1 [abstract 2])
The first phase III randomized trial in which the efficacy of direct decompressive surgery was evaluated in patients with metastatic SCC compared the standard 30 Gy in 3-Gy, uninterrupted, daily fractions with decompressive and stabilization surgery within 24 hours after diagnosis followed by the same radiotherapy started within 2 weeks. The trial was terminated early at interim analysis when early stopping rules were met regarding the primary end points of ambulatory rate and time ambulatory after treatment. Regarding the primary end point of ambulation, the combined treatment had a median ambulation time of 126 days, compared with 35 days for radiation alone (P = 0.006). Furthermore, baseline ambulatory and nonambulatory patients who had surgery and radiation had one-half the likelihood of being nonambulatory compared with those who had radiation alone. For nonambulatory patients, the combined-treatment patients had a significantly higher chance of regaining the ability to walk after therapy (56% vs. 19%; P = 0.03). Although the study included only 101 patients the results of this study challenges the accepted status quo of radiation alone in the management of metastatic SCC
Note:
(Shehadi JA et al. Eur Spine J 2007;16:1179–1192)
One-hundred twenty-five interventions in 87 patients with vertebral metastases in a population of 479 patients with breast cancer. Indications for spinal surgery (in patients able to tolerate it, and a life expectancy ≥3 months):
Results:
Of 76 patients who were ambulatory before surgery, 98% were also ambulatory after surgery
6/10 with pain before spinal surgery reduced to 2/10 with pain control for ≥12 months (p <0.001, significant compared to the population of patients without intervention)
Median follow-up of 13 months
Median survival after the first spinal surgery was 21 months (95% CI, 16–27 months)
39% of patients had complications; 26% considered significant
4. Chemotherapy ± Radiation
Chemotherapy can be used in combination with radiotherapy for treatment of SCC or alone for chemosensitive tumors including neuroblastoma, Ewing sarcoma, osteogenic sarcoma, germ cell tumors, and lymphomas in patients who are not candidates for surgery or radiation
5. Vertebroplasty (injecting cement percutaneously to treat a spinal metastasis with a risk of fracture [Anselmetti GC et al. Cardiovasc Intervent Radiol 2007;30:441–447; Bròdano GB et al. Eur Rev Med Pharmacol Sci 2007;11:91–100])
Effective at relieving pain
Increases spinal stability
Can help prevent the risk of fracture
Allows for radiotherapy to be delivered within a few days
6. Balloon kyphoplasty
(Berenson J et al. Lancet Oncol 2011;12:225–235)
For painful vertebral compression fractures, can provide rapid pain relief
Can improve neurological function when compared with a nonsurgical strategy
Allows for radiotherapy to be delivered within a few days