- Email: [email protected]
Surgical treatment and outcomes of metastatic breast cancer to the spine
Journal of Clinical Neuroscience 18 (2011) 1336–1339
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Surgical treatment and outcomes of metastatic breast cancer to the spine Brian P. Walcott a,⇑, Gregory L. Cvetanovich b, Zachary R. Barnard a, Brian V. Nahed a, Kristopher T. Kahle a, William T. Curry a,1 a b
Department of Neurosurgery, Massachusetts General Hospital, 55 Fruit St., White Building Room 502, Boston, MA 02114, USA Harvard Medical School, Boston, MA, USA
a r t i c l e
i n f o
Article history: Received 13 January 2011 Accepted 22 February 2011
Keywords: Breast neoplasms Neoplasm metastasis Spine Surgery
a b s t r a c t Metastatic vertebral body and spinal epidural lesions cause significant pain and neurological morbidity and negatively impact quality of life and survival. In instances of metastatic epidural spinal cord compression, treatment typically involves surgery and radiotherapy. The incidence of spinal metastases in breast cancer patients is high. In the light of recent improvements in survival among some patients with breast cancer, we reviewed the treatments and outcomes for patients with breast cancer who presented to our institution with metastatic epidural spinal cord compression. We identified all patients undergoing open surgery for the treatment of breast cancer metastases to the spine at our center from 1 January 2001 to 31 December 2009. We retrospectively reviewed records for the details of medical history, treatment, surgery, radiographic imaging, and follow-up. The Death Master File from the United States Social Security Administration was queried to identify the date of death where the medical record was incomplete. Outcomes were assessed by overall survival as well as preoperative and postoperative ambulatory status, bladder function, and the American Spinal Injury Association impairment classification system (ASIA). A total of 15 female patients were identified as having surgical intervention directly related to breast cancer metastasis to the spine. Most lesions (12/15) were located in the anterior vertebral column (vertebral body and/or pedicle). Two patients required re-operation, one for epidural fluid collection and one for infection. Roughly half of the patients (8/15) had well-controlled systemic disease at the time of surgery. Five patients had non-contiguous metastatic lesions elsewhere in the spine. Median survival following surgery was 1025 days; control of systemic disease did not predict duration of postoperative survival. Seven patients had documented improvement in their ability to ambulate in the first 30 days following surgery. Bladder function was preserved in all. No patient deteriorated; and five patients had postoperative improvement of their ASIA impairment scale grade. We concluded that aggressive therapy, including surgery, is warranted for patients with symptomatic metastatic epidural spinal cord compression from breast cancer, including in the setting of advanced and progressive systemic disease. Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction The spine is the commonest site for skeletal metastasis in patients with breast cancer,1–4 and up to half of these patients develop pain or neurological deficit related to pathological fracture, direct spinal cord compression, or a combination of the two.5 A recent prospective, randomized controlled trial has firmly established urgent surgery in the treatment paradigm for patients with focal metastatic spinal cord compression.6 Less established recommendations for spinal surgery have been made for metastatic disease associated with pain in non-compressive spinal lesions, multi-focal spinal disease, spinal metastatic disease with poor systemic control, and metastatic disease with impending ⇑ Corresponding author. Tel.: +1 617 726 2000, fax: +1 617 643 4113. 1
E-mail address: [email protected] (B.P. Walcott). Senior author
0967-5868/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2011.02.020
mechanical instability. It is generally accepted that life expectancy drives treatment regimens for spine metastasis.7 Therefore, it is necessary to specifically evaluate the efficacy of spinal surgery for breast cancer metastasis in the light of new therapies such as targeted agents, hormone manipulation, and bisphosphonates. 8–12 Herein, we update the assessment of outcomes for patients undergoing surgery for metastatic breast cancer to the spine.
2. Methods The Institutional Review Board (IRB) approval was obtained from the Partners Human Research Committee and the Massachusetts General Hospital IRB for protocol 2009-P-000027/1 (assurance #FWA00003136). A retrospective review was performed covering patients undergoing spinal surgery for metastatic breast cancer between 1 January 2001 and 30 January 2009. The complete
1337
B.P. Walcott et al. / Journal of Clinical Neuroscience 18 (2011) 1336–1339
medical records were reviewed for the details of medical history, treatment, surgery, radiographic imaging, and follow-up. The Death Master File from the United States Social Security Administration was queried to identify the date of death in all instances where the medical record was incomplete.13 The IBM Statistical Package for the Social Sciences Statistics Base software (SPSS Inc., Chicago, IL, USA) was used for data analysis. Patient characteristics analyzed included age and demographics, diagnostic interval, and burden of systemic disease. Patients without evidence of metastases at other sites or who were not undergoing therapy for progressive breast cancer at the time of presentation were considered to have ‘‘stable’’ systemic disease. Ambulatory status and American Spinal Injury Association (ASIA)14 impairment classification were assessed both at the time of presentation and post-operatively. Patients with complete spinal cord injury, ASIA ‘‘A’’, were excluded from analysis. Surgical complications were tallied, and overall survival was calculated from the day of surgery. Comparisons of survival curves were performed with the Log-Rank (Mantel–Cox) Test. Pearson product-moment correlation coefficients were generated to assess the significance of correlation between dataset values and survival.
Table 2 Type of surgery in patients who underwent surgical treatment for metastatic breast cancer to the spine
3. Results A total of 15 female patients were identified as having had surgical intervention directly related to epidural spinal cord compression from breast cancer metastasis (Table 1). The majority of lesions (12/15) were located in the anterior vertebral column (vertebral body or pedicle). Surgical approaches varied according to lesion characteristics, with lesions occurring anterior to the posterior elements being addressed directly (Table 2). More than half of the patients (8/15) had good control of systemic disease. Five patients had non-contiguous metastatic lesions elsewhere in their spine. One patient was lost to follow-up. Fourteen patients were identified for analyses of outcomes. Median survival following surgery was 1025 days (range = 99–2192 days). Seven patients had documented improvement in their ability to ambulate in the first 30 days following surgery. Four patients suffered surgical complications including cerebrospinal fluid leak, pulmonary embolism, wound infection, and hardware failure. Bladder function was pre-
Anterior/ posterior location
Type of surgery
1
Anterior
2
Anterior
3
Anterior
4
Anterior
5
Anterior
6 7 8
Anterior Posterior Anterior
9 10 11
Posterior Anterior Anterior
12
Anterior
13 14 15
Anterior Anterior Posterior
Anterior approach corpectomy, posterior approach fusion Transpedicular corpectomy, posterior approach fusion Transpedicular corpectomy, posterior approach fusion Anterior approach corpectomy, posterior approach fusion Preoperative embolization, corpectomy (retroperitoneal), anterior approach fusion Preoperative embolization, laminectomy Laminectomy, posterior approach fusion Anterior approach corpectomy, anterior and posterior approach fusion Laminectomy Posterior approach fusion Transpedicular corpectomy, posterior approach fusion Transpedicular corpectomy, posterior approach fusion Laminectomy Occipital cervical fusion Laminectomy and posterior approach fusion
served in all. No patient deteriorated neurologically; and five patients improved in terms of their ASIA score (D to E). There was no significant difference in median survival between patient groups with good (1070 days; 95% confidence interval [CI], 823–1114 days) or poor (1007 days; 95% CI, 302–1570 days) systemic control (p = 0.56, Fig. 1A). Change in ambulatory status predicted overall survival. Patients with a preoperative neurological deficit that did not improve had significantly worse median survival (407 days; 95% CI, 99–1114 days), than those who had either no deficit or who improved after decompression (1570 days; 95% CI, 899–1570 days; p < 0.005, Fig. 1B). The presence or absence of a surgical complication also defined two groups with a statistically significant overall survival. The group that had a surgical complication had a median survival of 395 days (95% CI, 99–1025 days)
Table 1 Characteristics of patients who underwent surgical treatment for metastatic breast cancer to the spine Patient No.
*
Age (years)
ER/PR
Her2/neu disease
Primary cancer
Control of systemic disease
Diabetes
Obesity
Smoker (active)
Smoker (pack years)
Neurological symptoms
Location of metastases
1
66
⁄
⁄
Ductal
Good
No
Yes
Yes
40
Lumbar
2 3 4
57 62 58
Yes No Yes
No Yes No
Lobular Ductal Ductal
Good Poor Good
No No No
No Yes No
No Yes Yes
0 40 15
5
61
Yes
No
Ductal
Good
No
No
No
40
Pain, weakness, sensation Pain Pain, sensation Pain, weakness, sensation Pain
6
51
Yes
No
Ductal
Poor
No
No
No
0
Pain, weakness
7
53
Yes
No
Ductal
Poor
Yes
Yes
No
0
Pain, sensation
8 9 0 11
71 55 49 44
Yes Yes Yes Yes
Yes No Yes Yes
Ductal Ductal Lobular Ductal
Good Poor Poor Good
No No No No
No No No Yes
No No No No
0 5 0 0
Pain Pain, weakness Pain Pain
12 13
76 39
Yes Yes
No Yes
Ductal Ductal
Good Poor
No No
Yes No
No No
0 2
14 15
74 81
⁄
⁄
Poor Good
No No
No No
0
No
Lobular Ductal
No
Yes
⁄
⁄
Pain, sensation Pain, weakness, sensation Pain Weakness
Information not available.
Thoracic Thoracic Cervical Thoracic, lumbar Thoracic, lumbar Cervical, thoracic Thoracic Cervical Cervical Cervical, thoracic Thoracic Thoracic Cervical Thoracic
1338
B.P. Walcott et al. / Journal of Clinical Neuroscience 18 (2011) 1336–1339
Fig. 1. Percentage survival graphs for patients who underwent surgical treatment for metastatic breast cancer to the spine showing: (A) no difference in survival between patients with good and poor systemic control (p = 0.56); (B) a significant difference in survival between patients with a deficit and no improvement following surgery compared to the group with no deficit or improvement following surgery (p = 0.0017); and (C) patients suffering surgical complications had significantly poorer survival than those who did not (p = 0.0052).
whereas the remainder had a median survival of 1570 days (95% CI, 407–1570 days; p = 0.005, Fig. 1C). Other variables, such as the length of time between the original breast cancer diagnosis and diagnosis of the epidural metastasis, or age at the time of surgery, did not correlate with survival (p-values 0.4088 and 0.3098, respectively). 4. Discussion The overall survival for a combination of direct surgery and radiation therapy for a compressive spinal epidural metastasis lesion has been reported to be 126 days in a large heterogeneous series.6 This study did report that a primary diagnosis of breast cancer was a significant predictor of enhanced survival but did not disclose the details. Subsequent retrospective reviews looking at breast cancer specifically have estimated a median survival time after initial spinal surgery to be 21 months.15 The survival data in
this report is encouraging and likely reflects the combined effects of aggressive decompressive and reconstructive surgery, radiation, and improved systemic therapies. While it is likely that patients were selected for surgery in our study because of various perceived favorable clinical attributes, the outcomes still reflect a cohort of all patients treated; including those with significant systemic disease, multi-level spinal disease, and advanced age. In these patients, the goal of surgery is to reduce or eliminate spinal cord compression while preserving and/or restoring mechanical stability. By restoring the mechanical needs of the spinal elements destroyed by the cancer, pain is often reduced and mobility increased.16 While stereotactic radiosurgery is also used to treat metastatic spine tumors with favorable outcomes, it has not proven superior to surgery in the immediate treatment of a compressive syndrome.17 Stereotactic radiosurgery for the treatment of breast cancer metastasis to the spine has been specifically studied and found effective, especially for those with solitary sites of spine involvement.18 Radiosurgery remains an option for tumor control in patients who choose not to have surgery or are deemed not to be suitable surgical candidates. There may also be a role for radiosurgery following decompressive surgery.19 Evaluating cancer patients as candidates for major spine surgery must be done in the context of prognosis. A modified Tokuhashi score has been shown to assist in decision-making based on reliable estimators of life expectancy in patients with spinal metastases secondary to breast cancer.20 A 2001 study reports that patients with bony breast cancer metastases undergoing surgery (including 14 spine patients) have an estimated survival of 6 months.21 However, more recently, long-term outcomes in these patients appear to be improving. Although bony metastases clearly reflect the existence of widespread disease, their presence does not necessarily predict disease trajectory. In a 2007 study of 87 patients with breast cancer metastatic to the spine, aggressive surgical management provided significant pain relief and preservation or improvement of neurological function in most patients. Median survival for the 18 patients who underwent surgery was 21 months (95% CI, 16–27 months).15 These data, in conjunction with that presented here, lends support to aggressive surgical management in patients with breast cancer in particular. In congruence with our study, the concomitant presence of visceral lesions or multi-focal bony disease did not have prognostic significance.22 While patients with complete spinal cord injury were excluded from this analysis, they may benefit from surgical stabilization as a means to palliate their pain. There are limitations to this study related to its retrospective nature. Assessment of pain, objective measures of ambulation, and quality of life measures could not be obtained. We could not directly asses the impact of specific post-operative therapies given their variety and the relatively small number of patients. Our analysis was limited to patients who had undergone surgery for symptomatic disease; accordingly, there was no control group with similar characteristics that did not undergo surgery. For instance, surprisingly, none of the patients in this cohort had ‘‘triple-negative’’ (estrogen receptor, progesterone receptor, and Her2/neu) disease. Patients with the most aggressive systemic disease may not have been chosen for surgery. Also, although we were able to stratify patients by systemic disease status, surgical complications, and neurological improvement, we were unable to account for the interplay between these factors and others because the small number of patients reduced the power of multivariate models.
5. Conclusion Decompressive surgery and spine stabilization is effective in patients with breast cancer metastasis to the spine with a tolerable
B.P. Walcott et al. / Journal of Clinical Neuroscience 18 (2011) 1336–1339
rate of complications. Furthermore, surgery is associated with improved neurological function and, likely, overall survival. The existence of progressive systemic disease should not be a contradiction to aggressive surgery. References 1. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin 2007;57:43–66. 2. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006;12:6243s–9s. 3. Asdourian PL, Weidenbaum M, DeWald RL, et al. The pattern of vertebral involvement in metastatic vertebral breast cancer. Clin Orthop Relat Res 1990;164–70. 4. Major P, Cook R, Lipton A, et al. Natural history of malignant bone disease in breast cancer and the use of cumulative mean functions to measure skeletal morbidity. BMC Cancer 2009;9:272. 5. Hortobagyi GN, Theriault RL, Lipton A, et al. Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group. J Clin Oncol 1998;16:2038–44. 6. Patchell RA, Tibbs PA, Regine WF, et al. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet 2005;366:643–8. 7. Tokuhashi Y, Ajiro Y, Umezawa N. Outcome of treatment for spinal metastases using scoring system for preoperative evaluation of prognosis. Spine 2009;34:69–73. 8. Howell A, Cuzick J, Baum M, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 2005;365:60–2. 9. Gnant M, Mlineritsch B, Schippinger W, et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 2009;360:679–91. 10. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357:2666–76.
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11. Lewis Phillips GD, Li G, Dugger DL, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody–cytotoxic drug conjugate. Cancer Res 2008;68:9280–90. 12. Di Cosimo S, Baselga J. Management of breast cancer with targeted agents: importance of heterogeneity [corrected]. Nat Rev Clin Oncol 2010;7:139–47. 13. Social Security Death Master File [Internet]. The US Depatment of Commerce National Technical Information Service; Available from: http://www.ntis.gov/ products/ssa-dmf.aspx. 14. Maynard FM, Bracken MB, Creasey G, et al. International standards for neurological and functional classification of spinal cord injury. American Spinal Injury Association. Spinal Cord 1997;35:266–74. 15. Shehadi JA, Sciubba DM, Suk I, et al. Surgical treatment strategies and outcome in patients with breast cancer metastatic to the spine: a review of 87 patients. Eur Spine J 2007;16:1179–92. 16. Fürstenberg CH, Wiedenhöfer B, Gerner HJ, et al. The effect of early surgical treatment on recovery in patients with metastatic compression of the spinal cord. J Bone Joint Surg Br 2009;91:240–4. 17. Gagnon GJ, Nasr NM, Liao JJ, et al. Treatment of spinal tumors using cyberknife fractionated stereotactic radiosurgery: pain and quality-of-life assessment after treatment in 200 patients. Neurosurgery 2009;64:297–306. discussion 306–307. 18. Gerszten PC, Burton SA, Welch WC, et al. Single-fraction radiosurgery for the treatment of spinal breast metastases. Cancer 2005;104:2244–54. 19. Moulding HD, Elder JB, Lis E, et al. Local disease control after decompressive surgery and adjuvant high-dose single-fraction radiosurgery for spine metastases. J Neurosurg Spine 2010;13:87–93. 20. Ulmar B, Richter M, Cakir B, et al. The Tokuhashi score: significant predictive value for the life expectancy of patients with breast cancer with spinal metastases. Spine 2005;30:2222–6. 21. Wedin R, Bauer HC, Rutqvist LE. Surgical treatment for skeletal breast cancer metastases: a population-based study of 641 patients. Cancer 2001;92:257–62. 22. Sciubba DM, Gokaslan ZL, Suk I, et al. Positive and negative prognostic variables for patients undergoing spine surgery for metastatic breast disease. Eur Spine J 2007;16:1659–67.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Surgical treatment and outcomes of metastatic breast cancer to the spine Brian P. Walcott a,⇑, Gregory L. Cvetanovich b, Zachary R. Barnard a, Brian V. Nahed a, Kristopher T. Kahle a, William T. Curry a,1 a b
Department of Neurosurgery, Massachusetts General Hospital, 55 Fruit St., White Building Room 502, Boston, MA 02114, USA Harvard Medical School, Boston, MA, USA
a r t i c l e
i n f o
Article history: Received 13 January 2011 Accepted 22 February 2011
Keywords: Breast neoplasms Neoplasm metastasis Spine Surgery
a b s t r a c t Metastatic vertebral body and spinal epidural lesions cause significant pain and neurological morbidity and negatively impact quality of life and survival. In instances of metastatic epidural spinal cord compression, treatment typically involves surgery and radiotherapy. The incidence of spinal metastases in breast cancer patients is high. In the light of recent improvements in survival among some patients with breast cancer, we reviewed the treatments and outcomes for patients with breast cancer who presented to our institution with metastatic epidural spinal cord compression. We identified all patients undergoing open surgery for the treatment of breast cancer metastases to the spine at our center from 1 January 2001 to 31 December 2009. We retrospectively reviewed records for the details of medical history, treatment, surgery, radiographic imaging, and follow-up. The Death Master File from the United States Social Security Administration was queried to identify the date of death where the medical record was incomplete. Outcomes were assessed by overall survival as well as preoperative and postoperative ambulatory status, bladder function, and the American Spinal Injury Association impairment classification system (ASIA). A total of 15 female patients were identified as having surgical intervention directly related to breast cancer metastasis to the spine. Most lesions (12/15) were located in the anterior vertebral column (vertebral body and/or pedicle). Two patients required re-operation, one for epidural fluid collection and one for infection. Roughly half of the patients (8/15) had well-controlled systemic disease at the time of surgery. Five patients had non-contiguous metastatic lesions elsewhere in the spine. Median survival following surgery was 1025 days; control of systemic disease did not predict duration of postoperative survival. Seven patients had documented improvement in their ability to ambulate in the first 30 days following surgery. Bladder function was preserved in all. No patient deteriorated; and five patients had postoperative improvement of their ASIA impairment scale grade. We concluded that aggressive therapy, including surgery, is warranted for patients with symptomatic metastatic epidural spinal cord compression from breast cancer, including in the setting of advanced and progressive systemic disease. Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction The spine is the commonest site for skeletal metastasis in patients with breast cancer,1–4 and up to half of these patients develop pain or neurological deficit related to pathological fracture, direct spinal cord compression, or a combination of the two.5 A recent prospective, randomized controlled trial has firmly established urgent surgery in the treatment paradigm for patients with focal metastatic spinal cord compression.6 Less established recommendations for spinal surgery have been made for metastatic disease associated with pain in non-compressive spinal lesions, multi-focal spinal disease, spinal metastatic disease with poor systemic control, and metastatic disease with impending ⇑ Corresponding author. Tel.: +1 617 726 2000, fax: +1 617 643 4113. 1
E-mail address: [email protected] (B.P. Walcott). Senior author
0967-5868/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2011.02.020
mechanical instability. It is generally accepted that life expectancy drives treatment regimens for spine metastasis.7 Therefore, it is necessary to specifically evaluate the efficacy of spinal surgery for breast cancer metastasis in the light of new therapies such as targeted agents, hormone manipulation, and bisphosphonates. 8–12 Herein, we update the assessment of outcomes for patients undergoing surgery for metastatic breast cancer to the spine.
2. Methods The Institutional Review Board (IRB) approval was obtained from the Partners Human Research Committee and the Massachusetts General Hospital IRB for protocol 2009-P-000027/1 (assurance #FWA00003136). A retrospective review was performed covering patients undergoing spinal surgery for metastatic breast cancer between 1 January 2001 and 30 January 2009. The complete
1337
B.P. Walcott et al. / Journal of Clinical Neuroscience 18 (2011) 1336–1339
medical records were reviewed for the details of medical history, treatment, surgery, radiographic imaging, and follow-up. The Death Master File from the United States Social Security Administration was queried to identify the date of death in all instances where the medical record was incomplete.13 The IBM Statistical Package for the Social Sciences Statistics Base software (SPSS Inc., Chicago, IL, USA) was used for data analysis. Patient characteristics analyzed included age and demographics, diagnostic interval, and burden of systemic disease. Patients without evidence of metastases at other sites or who were not undergoing therapy for progressive breast cancer at the time of presentation were considered to have ‘‘stable’’ systemic disease. Ambulatory status and American Spinal Injury Association (ASIA)14 impairment classification were assessed both at the time of presentation and post-operatively. Patients with complete spinal cord injury, ASIA ‘‘A’’, were excluded from analysis. Surgical complications were tallied, and overall survival was calculated from the day of surgery. Comparisons of survival curves were performed with the Log-Rank (Mantel–Cox) Test. Pearson product-moment correlation coefficients were generated to assess the significance of correlation between dataset values and survival.
Table 2 Type of surgery in patients who underwent surgical treatment for metastatic breast cancer to the spine
3. Results A total of 15 female patients were identified as having had surgical intervention directly related to epidural spinal cord compression from breast cancer metastasis (Table 1). The majority of lesions (12/15) were located in the anterior vertebral column (vertebral body or pedicle). Surgical approaches varied according to lesion characteristics, with lesions occurring anterior to the posterior elements being addressed directly (Table 2). More than half of the patients (8/15) had good control of systemic disease. Five patients had non-contiguous metastatic lesions elsewhere in their spine. One patient was lost to follow-up. Fourteen patients were identified for analyses of outcomes. Median survival following surgery was 1025 days (range = 99–2192 days). Seven patients had documented improvement in their ability to ambulate in the first 30 days following surgery. Four patients suffered surgical complications including cerebrospinal fluid leak, pulmonary embolism, wound infection, and hardware failure. Bladder function was pre-
Anterior/ posterior location
Type of surgery
1
Anterior
2
Anterior
3
Anterior
4
Anterior
5
Anterior
6 7 8
Anterior Posterior Anterior
9 10 11
Posterior Anterior Anterior
12
Anterior
13 14 15
Anterior Anterior Posterior
Anterior approach corpectomy, posterior approach fusion Transpedicular corpectomy, posterior approach fusion Transpedicular corpectomy, posterior approach fusion Anterior approach corpectomy, posterior approach fusion Preoperative embolization, corpectomy (retroperitoneal), anterior approach fusion Preoperative embolization, laminectomy Laminectomy, posterior approach fusion Anterior approach corpectomy, anterior and posterior approach fusion Laminectomy Posterior approach fusion Transpedicular corpectomy, posterior approach fusion Transpedicular corpectomy, posterior approach fusion Laminectomy Occipital cervical fusion Laminectomy and posterior approach fusion
served in all. No patient deteriorated neurologically; and five patients improved in terms of their ASIA score (D to E). There was no significant difference in median survival between patient groups with good (1070 days; 95% confidence interval [CI], 823–1114 days) or poor (1007 days; 95% CI, 302–1570 days) systemic control (p = 0.56, Fig. 1A). Change in ambulatory status predicted overall survival. Patients with a preoperative neurological deficit that did not improve had significantly worse median survival (407 days; 95% CI, 99–1114 days), than those who had either no deficit or who improved after decompression (1570 days; 95% CI, 899–1570 days; p < 0.005, Fig. 1B). The presence or absence of a surgical complication also defined two groups with a statistically significant overall survival. The group that had a surgical complication had a median survival of 395 days (95% CI, 99–1025 days)
Table 1 Characteristics of patients who underwent surgical treatment for metastatic breast cancer to the spine Patient No.
*
Age (years)
ER/PR
Her2/neu disease
Primary cancer
Control of systemic disease
Diabetes
Obesity
Smoker (active)
Smoker (pack years)
Neurological symptoms
Location of metastases
1
66
⁄
⁄
Ductal
Good
No
Yes
Yes
40
Lumbar
2 3 4
57 62 58
Yes No Yes
No Yes No
Lobular Ductal Ductal
Good Poor Good
No No No
No Yes No
No Yes Yes
0 40 15
5
61
Yes
No
Ductal
Good
No
No
No
40
Pain, weakness, sensation Pain Pain, sensation Pain, weakness, sensation Pain
6
51
Yes
No
Ductal
Poor
No
No
No
0
Pain, weakness
7
53
Yes
No
Ductal
Poor
Yes
Yes
No
0
Pain, sensation
8 9 0 11
71 55 49 44
Yes Yes Yes Yes
Yes No Yes Yes
Ductal Ductal Lobular Ductal
Good Poor Poor Good
No No No No
No No No Yes
No No No No
0 5 0 0
Pain Pain, weakness Pain Pain
12 13
76 39
Yes Yes
No Yes
Ductal Ductal
Good Poor
No No
Yes No
No No
0 2
14 15
74 81
⁄
⁄
Poor Good
No No
No No
0
No
Lobular Ductal
No
Yes
⁄
⁄
Pain, sensation Pain, weakness, sensation Pain Weakness
Information not available.
Thoracic Thoracic Cervical Thoracic, lumbar Thoracic, lumbar Cervical, thoracic Thoracic Cervical Cervical Cervical, thoracic Thoracic Thoracic Cervical Thoracic
1338
B.P. Walcott et al. / Journal of Clinical Neuroscience 18 (2011) 1336–1339
Fig. 1. Percentage survival graphs for patients who underwent surgical treatment for metastatic breast cancer to the spine showing: (A) no difference in survival between patients with good and poor systemic control (p = 0.56); (B) a significant difference in survival between patients with a deficit and no improvement following surgery compared to the group with no deficit or improvement following surgery (p = 0.0017); and (C) patients suffering surgical complications had significantly poorer survival than those who did not (p = 0.0052).
whereas the remainder had a median survival of 1570 days (95% CI, 407–1570 days; p = 0.005, Fig. 1C). Other variables, such as the length of time between the original breast cancer diagnosis and diagnosis of the epidural metastasis, or age at the time of surgery, did not correlate with survival (p-values 0.4088 and 0.3098, respectively). 4. Discussion The overall survival for a combination of direct surgery and radiation therapy for a compressive spinal epidural metastasis lesion has been reported to be 126 days in a large heterogeneous series.6 This study did report that a primary diagnosis of breast cancer was a significant predictor of enhanced survival but did not disclose the details. Subsequent retrospective reviews looking at breast cancer specifically have estimated a median survival time after initial spinal surgery to be 21 months.15 The survival data in
this report is encouraging and likely reflects the combined effects of aggressive decompressive and reconstructive surgery, radiation, and improved systemic therapies. While it is likely that patients were selected for surgery in our study because of various perceived favorable clinical attributes, the outcomes still reflect a cohort of all patients treated; including those with significant systemic disease, multi-level spinal disease, and advanced age. In these patients, the goal of surgery is to reduce or eliminate spinal cord compression while preserving and/or restoring mechanical stability. By restoring the mechanical needs of the spinal elements destroyed by the cancer, pain is often reduced and mobility increased.16 While stereotactic radiosurgery is also used to treat metastatic spine tumors with favorable outcomes, it has not proven superior to surgery in the immediate treatment of a compressive syndrome.17 Stereotactic radiosurgery for the treatment of breast cancer metastasis to the spine has been specifically studied and found effective, especially for those with solitary sites of spine involvement.18 Radiosurgery remains an option for tumor control in patients who choose not to have surgery or are deemed not to be suitable surgical candidates. There may also be a role for radiosurgery following decompressive surgery.19 Evaluating cancer patients as candidates for major spine surgery must be done in the context of prognosis. A modified Tokuhashi score has been shown to assist in decision-making based on reliable estimators of life expectancy in patients with spinal metastases secondary to breast cancer.20 A 2001 study reports that patients with bony breast cancer metastases undergoing surgery (including 14 spine patients) have an estimated survival of 6 months.21 However, more recently, long-term outcomes in these patients appear to be improving. Although bony metastases clearly reflect the existence of widespread disease, their presence does not necessarily predict disease trajectory. In a 2007 study of 87 patients with breast cancer metastatic to the spine, aggressive surgical management provided significant pain relief and preservation or improvement of neurological function in most patients. Median survival for the 18 patients who underwent surgery was 21 months (95% CI, 16–27 months).15 These data, in conjunction with that presented here, lends support to aggressive surgical management in patients with breast cancer in particular. In congruence with our study, the concomitant presence of visceral lesions or multi-focal bony disease did not have prognostic significance.22 While patients with complete spinal cord injury were excluded from this analysis, they may benefit from surgical stabilization as a means to palliate their pain. There are limitations to this study related to its retrospective nature. Assessment of pain, objective measures of ambulation, and quality of life measures could not be obtained. We could not directly asses the impact of specific post-operative therapies given their variety and the relatively small number of patients. Our analysis was limited to patients who had undergone surgery for symptomatic disease; accordingly, there was no control group with similar characteristics that did not undergo surgery. For instance, surprisingly, none of the patients in this cohort had ‘‘triple-negative’’ (estrogen receptor, progesterone receptor, and Her2/neu) disease. Patients with the most aggressive systemic disease may not have been chosen for surgery. Also, although we were able to stratify patients by systemic disease status, surgical complications, and neurological improvement, we were unable to account for the interplay between these factors and others because the small number of patients reduced the power of multivariate models.
5. Conclusion Decompressive surgery and spine stabilization is effective in patients with breast cancer metastasis to the spine with a tolerable
B.P. Walcott et al. / Journal of Clinical Neuroscience 18 (2011) 1336–1339
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