Hardware failure in patients with metastatic cancer to the spine

Journal of Clinical Neuroscience xxx (2017) xxx–xxx

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Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn

Case Study

Hardware failure in patients with metastatic cancer to the spine Rachel Pedreira a, Nancy Abu-Bonsrah a, A. Karim Ahmed a, Rafael De la Garza-Ramos a, C. Rory Goodwin a, Ziya L. Gokaslan b, Justin Sacks c, Daniel M. Sciubba a,⇑ a

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, RI, USA c Department of Plastic Surgery and Reconstruction, The Johns Hopkins University School of Medicine Baltimore, MD, USA b

a r t i c l e

i n f o

Article history: Received 23 March 2017 Accepted 22 May 2017 Available online xxxx Keywords: Hardware failure Spinal metastases Radiation

a b s t r a c t Background: The spine is the most common site of skeletal metastases, affecting approximately 30% of individuals with cancer. The aim of surgical treatment for metastatic spine disease is generally palliative to address pain and/or neurologic compromise, significantly improving patients’ quality of life. Patients with metastatic spine disease, however, represent a vulnerable cohort and may have comorbidities or previous treatments that impair the structural integrity of spinal hardware. As such, identifying factors that may contribute to hardware failure is an essential component in treating individuals with metastatic spine disease. Objective: The aim of this study was to identify pre-operative risk factors associated with hardware failure in patients undergoing surgical treatment for metastatic spine disease. Methods: A retrospective cohort study was conducted to include patients surgically treated for metastatic spine tumors between 2003 and 2013, at a single institution. A univariate analysis was initially performed to identify associated factors. Any associated factor with a p-value <0.20 was included in the multivariate analysis. Results: 3 patients (1.9%), of the 159 patients included in the study, had failure of the spine instrumentation. 1 patient had metastatic prostate cancer, and 2 had metastatic breast cancer. Patient demographics, co-morbidities, tumor location, and primary tumor etiology were not found to be statistically significant, with respect to hardware failure. Predictive factors included in the multivariate model were other bone metastasis, visceral metastasis, brain metastasis, Modified Rankin scale, previous systemic chemotherapy, previous radiation to the spine, and mean survival. Previous radiation to the spine was the only factor to be significantly associated (p = 0.029), present in all three patients with hardware failure. Of note, there was a trend indicating that patients with longer life expectancies were more likely to experience hardware failure (mean survival of 16.7 months in non-failure cohort vs. 33 months in failure cohort), though this did not achieve statistical significance due to the limited sample size of patients with hardware failure. Conclusion: Hardware failure is a risk for all patients who undergo instrumentation following resection for metastatic spine tumors. This study identified that pre-operative radiation may increase the risk for hardware failure in this population. Ó 2017 Elsevier Ltd. All rights reserved.

1. Introduction The spinal column is the most common site of skeletal metastases and approximately 30% of individuals with cancer develop metastatic lesions [1,2]. Treatment for metastatic lesions to the spine is generally palliative and may include radiation, chemotherapy, analgesia, hormonal therapy, and surgery [1]. Surgical ⇑ Corresponding author at: 600 North Wolfe Street, Meyer 5-185, Baltimore, MD 21287, USA. Fax: +1 410 502 5768. E-mail address: [email protected] (D.M. Sciubba).

treatment for metastatic spine disease can address pain and/or neurologic compromise, significantly improving patients’ quality of life [2,3]. Despite the best attempt by surgeons to alleviate pain and improve functionality for patients with metastatic spine disease, adverse events requiring reoperation may occur [4,5]. These include hardware failure, CSF leakage, wound infection, and nonunion [6–8]. As such, patients with metastatic spine disease represent a vulnerable cohort and may have comorbidities or previous treatments that impair the structural integrity of spine hardware.

http://dx.doi.org/10.1016/j.jocn.2017.05.038 0967-5868/Ó 2017 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Pedreira R et al. Hardware failure in patients with metastatic cancer to the spine. J Clin Neurosci (2017), http://dx.doi. org/10.1016/j.jocn.2017.05.038

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While more probable in primary tumor patients given their longer life expectancy [9], patients with metastatic tumors face the undesirable possibility of construct hardware failure. This is a very costly [10] and painful complication that comes with the possibility of neurological compromise, and may necessitate larger revision operations. Cited rates of hardware failure in the literature range from 2.8% [11] to 37% [12] and vary according to the type and location of the resection performed. Identifying factors that may contribute to hardware failure is an essential component in treating individuals with metastatic spine disease. In this study we have explored possible variables associated with hardware failure in patients undergoing resection of metastatic spinal tumors and subsequent spinal column reconstruction. 2. Methods 2.1. Study design and inclusion criteria A retrospective chart review was conducted, after IRB approval (IRB number NA_00067508), of all patients who underwent surgery for metastatic spinal tumors presenting to a single institution between 2003 and 2012. The inclusion criteria consisted of patients (1) aged 18–100 years at the time of surgery; (2) at least 3 months of follow-up after the initial spine operation; (3) complete electronic medical record; and (4) surgical resection of a metastatic spine lesion with a tumor etiology frequently seen during this time period (n  5 patients). This included lung, breast, kidney, bone marrow (multiple myeloma or plasmacytoma), prostate, colorectal, gynecological (uterus or cervix), and skin (melanoma). 2.2. Recorded data Patient data including age, gender, race, and co-morbidities were collected by reviewing patient charts. Tumor specific data (location, type, number of metastatic sites) and treatment history such as previous chemotherapy and/or radiation were also extracted through review of patient charts and surgical records. The primary outcome measures evaluated in this study were mean post-operative survival time and the incidence of hardware failure, defined as acute or subacute deformity (kyphosis, fracture) or pain as a result of broken rods, broken/loosened/pulled out screws, or displacement of implanted hardware, that eventually led to operative revision. 2.3. Statistical analysis Demographic data is reported as means with standard deviations. Frequencies were compared with chi-squared testing and means were compared with one-way analysis of variance. A multivariate Cox proportional hazards model was used to identify independent factors associated with hardware failure; factors with a pvalue <0.200 on univariate analysis were included in this model. A p-value of <0.05 was considered significant. All analyses were performed using STATA SE 12 (StataCorp LP, College Station, Texas), or GraphPad Prism 6 (GraphPad Software Inc., La Jolla, California). 3. Results 3.1. Patient demographics 159 patients treated surgically for metastatic cancer to the spine were identified, 3 of which exhibited hardware failure requiring reoperation, suggesting an overall incidence of 1.8%. The average age of the patients reviewed without failure was

60 ± 12 and 65 ± 9 in patients with failure. 53.9% of the patients without hardware failure were male while two-thirds of the patients without hardware failure were female. All of the patients with hardware failure were of Caucasian ethnicity while within the non-failure group the 71.2% were Caucasian, 21.8% were African American, and the remaining patients were of other ethnicities (Table 1). Among all 159 patients, hypertension, coronary artery disease, and thromboembolic disease were the most common comorbidities observed. 3.2. Location and tumor etiology The most common location for metastases in patients without hardware failure was in the thoracic spine (51.9%) followed by the lumbar spine (20.5%). In the hardware failure cohort, metastases were either within the thoracic (66.7%) or thoracolumbar (33.3%) regions. Among the patients that did not experience hardware failure, the most common primary tumor etiology was lung (22.4%) followed closely by breast (18.6%) and kidney (16.7%) (Table 2). In hardware failure patients all the females presented with metastases from breast cancer and the male presented with prostate cancer metastases. 3.3. Factors affecting hardware failure All patients with hardware failure had undergone pre-operative radiation, which was found to be a significant factor related to hardware failure (p = 0.029). No other factors were found to be statistically significant predictors of hardware failure, however other trends were evident in the data. Mean survival in the patients without hardware failure was 16.7 ± 22.6 months, while in the cohort with hardware failure, mean survival was found to be 33 ± 30 months (Table 3). 3.3.1. Case 1 A 60-year-old female, with a five-year history of metastatic breast cancer (ER/PR negative, HER 2 positive), first presented to the neurosurgical spine service with persistent back pain at the level of T7–T8. Two years prior to this, she developed low back pain and was diagnosed with metastatic disease at T9–T10, for which she received radiation to the region. One year prior to her presentation to the neurosurgical service, she was diagnosed with metastatic disease at T7 and received stereotactic radiosurgery to T7.

Table 1 Patient demographics. 159 patients treated surgically for metastatic cancer to the spine were identified, 3 of which exhibited hardware failure requiring reoperation, suggesting an overall incidence of 1.8%. Parameter

No hardware failure

Hardware failure

p-Value

Patient data Number of cases Average age, years Age above 60 (%) Male sex (%)

156 60 ± 12 36.5 53.9

3 65 ± 9 33.3 33.3

Race Caucasian (%) African American (%) Other (%)

71.2 21.8 7.1

100.0 0.0 0.0

0.547

Co-morbidities Hypertension (%) Coronary artery disease (%) Thromboembolic disease (%) Renal disease (%) Diabetes mellitus (%) Hyperlipidemia (%) COPD (%)

35.3 12.5 7.9 2.7 16.5 21.7 9.9

66.7 33.3 0.0 0.0 0.0 0.0 0.0

0.262 0.286 0.612 0.775 0.443 0.363 0.566

0.386 0.909 0.480

Please cite this article in press as: Pedreira R et al. Hardware failure in patients with metastatic cancer to the spine. J Clin Neurosci (2017), http://dx.doi. org/10.1016/j.jocn.2017.05.038

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Table 2 Primary tumor etiology of 159 patients surgically treated for metastatic spine disease at a single institution. Parameter Location Cervical (%) Cervicothoracic (%) Thoracic (%) Thoracolumbar (%) Lumbar (%) Sacral (%) Tumor type Lung (%) Breast (%) Kidney (%) Bone marrow-multiple myeloma/plasmacytoma (%) Prostate (%) Colorectal (%) Gynecological (%) Skin (%)

No hardware failure

Hardware failure

p-Value

14.7 7.1 51.9 3.9 20.5 1.9

0.0 0.0 66.7 33.3 0.0 0.0

0.202

22.4 18.6 16.7 13.5

0.0 66.7 0.0 0.0

0.438

10.9 9.0 4.5 4.5

33.3 0.0 0.0 0.0

Table 3 Multivariate analysis of factor affecting hardware failure from 159 patients surgically treated for metastatic spine disease. Parameter

No hardware failure

Hardware failure

p-Value

Other bone metastasis Visceral metastasis Brain metastasis Modified Rankin scale, average Previous systemic chemotherapy Previous spine radiation Mean survival (months)

39.1 41.3 12.9 2.1 ± 1.1

33.3 0.0 0.0 2.0 ± 1.7

0.839 0.149 0.506 0.962

46.2

0.0

0.193

37.8 16.7 ± 22.6

100.0 33 ± 30

0.029* 0.450

However, the progressive back pain warranted further neurosurgical evaluation. At this time, she underwent posterior arthrodesis from T5 to T10 with an en bloc spondylectomy of T7–T8. Anterior reconstruction with a distractible titanium cage was performed from T6 to T9 and she did well following that operation. 18 months following her first spine surgery, she was found to have a highly unstable instrumentation failure with bilateral rod fractures and a kyphotic deformity (Fig. 1). The posterior hardware from T5 to T10 was replaced with left T5–T10 and right T4–T10 instrumentation. 47 months after her second spine surgery, she was found to have a fracture of the right-sided rod at the level of T8 with worsening kyphosis at T11 and back pain (Fig. 2). At that time, posterior arthrodesis from T5 to L3 was performed with a T11 corpectomy and T10–T12 titanium cage reconstruction (Fig. 3). She passed away 3 months later. 3.3.2. Case 2 A 60-year-old male with a 7-year history of prostate cancer presented to the neurosurgical spine service with back pain and myelopathy. Upon diagnosis of the primary tumor, he underwent prostatectomy with radiation. 6 months prior to his presentation to neurosurgery, he was diagnosed with a symptomatic pathological fracture at L1 for which he underwent a kyphoplasty (Fig. 4). The biopsy revealed adenocarcinoma, although his PSA level at that time was zero. Three months following kyphoplasty, he received focal radiation therapy to L1 and did well during the following weeks. Upon presentation to neurosurgery, the patient had been nonambulatory for two weeks, with bilateral lower extremity numbness, paresthesias, weakness, myelopathy, and T12 radiculopathies.

Fig. 1. A 60-year-old female underwent posterior T5–T10 arthrodesis and T6–T9 distractible titanium cage reconstruction for a solitary T7 metastatic breast cancer lesion (A). Sagittal topogram (B). Coronal topogram (C). Sagittal CT without contrast (D). Volume Rendered Technique (VRT) of bilateral fractured rods and kyphotic deformity, 18 months post-operatively (E). Sagittal CT without contrast of hardware failure.

Imaging revealed tumor infiltration from T9 to L3 vertebral bodies, with epidural spinal cord compression, most notably at T10–T11. He also had retropulsed fragments causing compression of the thecal sac at L1 and L3. He underwent bilateral laminectomies, decompression, and resection of the tumor at T10, T11, L1, and L3. Posterior transpedicular instrumentation was performed bilaterally at T8, T9, T10, T12, L2, and L4, skipping T11, L1 and L3. Two months following surgery, the patient presented with excruciating back pain and persistent proximal lower extremity weakness. He was found to have hardware failure at the bottom of L4, with a screw pulling out at one side and contralateral rod-screw dissociation. The posterior hardware was removed and a repeat fusion was performed extending from T8 to pelvis. He passed away 4 months later. 3.3.3. Case 3 A 74 year-old female with a 24-year history of breast cancer presented to the neurosurgical service for a solitary T5 metastatic lesion, with no other sites of distant metastasis. This was an incidental finding as she was not neurologically compromised, and was completely asymptomatic. For this reason, she underwent radiation therapy to the spine lesion and was subsequently followed. 11 months following radiation therapy, imaging revealed growth of the lesion with a compression fraction of the T5 vertebral body, and epidural spinal cord compression. Despite the imaging findings, the patient did not complain of any pain or weakness. Given the progression of the tumor, she underwent T3–T8 posterior arthrodesis with a T5 corpectomy, tumor resection, and anterior cage reconstruction (Fig. 5). A routine radiograph, 1 month post-operatively, demonstrated instrumentation failure consisting of cage migration and worsening kyphosis. The patient was

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Fig. 3. Third spine surger; revision of posterior hardware with T5–L3 instrumented arthrodesis, T10 corpectomy, and T10–T12 titanium cage reconstruction (A). Sagittal CT without contrast (B). Volume Rendering Technique (VRT).

Fig. 2. Revision of posterior hardware with left-sided T5–10 and right-sided T4– T10 instrumented arthrodesis (A). Sagittal CT without contrast (B). Coronal topogram (C). Sagittal plain radiograph of fractured right-sided rod, 47 months following second spine surgery (D). Sagittal CT without contrast of hardware failure and worsening kyphosis.

asymptomatic but underwent surgical revision for the highly unstable construct. The original hardware was removed, and replaced with instrumentation from T1 to T11. Methyl methacrylate augmentation and vertebroplasty of T1, T2, T3, T4, T7, T8, T9, and T10 were also performed (Fig. 6). She did well following this and passed away 48 months later.

Fig. 4. A 60-year-old male with a 7-year history of prostate cancer presented to the neurosurgical spine service for symptomatic pathologic fracture of L1. (A). Sagittal plain radiograph of L1 kyphoplasty. (B). Sagittal CT without contrast of L1 kyphoplasty. (C). Sagittal CT without contrast of T8–L4 fusion, with epidural tumor resection.

4. Discussion In patients with metastatic cancer to the spine, treatment is generally palliative and focused on improving quality of life by addressing the symptoms resulting from tumor growth and invasion [13]. These patients may undergo tumor resection and spinal column reconstruction as a means of providing pain relief, alleviating neurological symptoms, and gaining local tumor control. However, for patients with metastatic spinal cancer undergoing surgical treatment, hardware failure is a painful and highly morbid complication necessitating re-operation to prevent further neurologic compromise [14]. In an effort to gain an increased understanding of the need for revision surgery, the complications, and quality of life impairment associated with hardware failure, we investigated

Fig. 5. A 74 year-old female with a 24-year history of breast cancer presented to the neurosurgical service for a solitary T5 metastatic lesion (A). Sagittal plain radiograph of T5 compression fracture (B). Sagittal CT without contrast, 1 month post-op. (C). Coronal topogram, 1 month post-op.

Please cite this article in press as: Pedreira R et al. Hardware failure in patients with metastatic cancer to the spine. J Clin Neurosci (2017), http://dx.doi. org/10.1016/j.jocn.2017.05.038

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Fig. 6. Hardware failure consisting of distractible cage migration in a 75 year-old female with metastatic breast cancer, 11 months post-operatively (A). Lateral plain radiograph of distractible cage migration, 11 months post-op (B). AP radiograph of hardware failure (C). Lateral plain radiograph of revision surgery, T1–T11 posterior arthrodesis (D). AP plain radiograph of revision surgery.

key factors that may contribute to hardware failure in the population with metastatic spine disease. Hardware failure occurs due to application of stress that overcomes the biomechanical strength of the construct, and is a rare but potentially debilitating complication. In a retrospective clinical study by Amankulor et al. [15–21], 318 patients who received separation surgery for metastatic epidural spinal cord compression (MESCC) were reviewed for potential risk factors associated with hardware failure. The study found that rib resection leading to chest wall instability, and construct lengths longer than 6 contiguous vertebral segments were associated with hardware failure— factors that did not achieve statistical significance in the current study. The incidence of hardware failure was 2.8% (9/318), compared to 1.9% in the present study. Although the survival for patients with hardware failure was not reported in this study, the 309 patients without hardware failure had a mean overall survival of 399 days (13.3 months), comparable to a mean survival of 16.7 months seen in the non-failure cohort of the current study. 100% of the hardware failure patients in the current study had undergone prior radiation therapy to the spine as compared to 37.8% of patients in the group that did not experience hardware

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failure, suggesting that pre-operative spine radiation may be a factor associated with hardware failure (p = 0.029). In a systematic review by Mesfin et al. [23] to determine potential contributing factors for adverse events in the surgical management of patients with metastatic spine disease, fourteen articles identified preoperative radiation to be associated with surgical site infections and wound complications following surgery. Jandali et al. [24] published a case series of patients with hardware failure following surgical resection of primary spine tumors. All patients in the series received preoperative radiation to the lesion and required revision surgery after instrumentation failure. More specifically, radiation exposure has been shown to cause osteoradionecrosis – dysvascular bone necrosis and fibrous replacement [25,26]. Poorly vascularized and necrotic bone lacks integrity and as such provides an unstable foundation for hardware fixation, thus predisposing these irradiated patients to post-operative hardware failure. In addition to contributing to poor bony fusion, there is emerging evidence in the literature associating pre-operative radiation with poor post-operative paraspinous muscle healing [27]. Decreased strength in these muscle groups puts greater strain on spinal constructs therefore possibly contributing further to hardware failure. Notably, the literature shows that when combined with surgery, post-operative radiation spinal metastases is associated with improved patient quality of remaining life [22,28,29]. Thus, timing of radiotherapy appears to impact outcomes in this patient population and strong consideration must be given to the risk of hardware failure if radiation is delivered pre-operatively. The patients reviewed in this study that experienced hardware failure had a mean post-operative survival time of 33 months compared to 17 months for patients without hardware failure. While not a statistically significant difference in survival time (p = 0.450), this trend may explain why hardware failure was so rare in this population – with metastatic disease, patients tend to die before constructs have withstood stress significant enough to fail. Limitations of this study include those inherent in retrospective analysis of a small cohort investigated at a single institution. Though significant, we only saw three patients with failure. A larger cohort will need to be investigated to more definitively delineate causation. These patients were not treated with a uniform treatment algorithm and thus variations may have existed in their care that could have confounded the data. Particularly, the extent of resection was not controlled for in this population and no data was collected detailing pre and post-operative spinal instability. In addition, patients that had non-symptomatic hardware failure or patients too ill to undergo surgery are not represented in this cohort – as such there may have been cases of asymptomatic or untreated hardware failure. Finally, this study examined only a subset of potential factors thought to be associated with failure – other literature has cited additional factors like smoking, multiple comorbidities, and constructs greater than six levels as causes of mechanical failure [11,12,23,30].

5. Conclusions Patients with metastatic cancer to the spine experience tremendous morbidity and have limited life expectancies. Surgical resection of tumors can improve quality of life for these patients by reducing pain and alleviating neurological compromise. For these patients, the primary goal of surgery is palliative, thus survival prognosis and potential complications are weighed heavily in the decision to pursue surgery [31]. Instrumentation of the spine, however, introduces the potential for further morbidity related to hardware failure. In the current study, we found that preoperative radiation was significantly associated with hardware failure

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(p = 0.029). Data also revealed that survival for patients without hardware failure is, on average, nearly twice as long as for patients with hardware failure. While not significant in this data set, this trend suggests longer survival times may put patients with metastatic tumors at higher risk for experiencing this complication. Finally, within hardware failure patients, breast and prostate cancer were the most common primary tumor etiologies while lung cancer was the most common source of metastasis in the patients that did not suffer from hardware failure.

[11]

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General disclosures unrelated to the present work [15]

Rachel Pedreira, BA: None Nancy Abu-Bonsrah, BS: None A. Karim Ahmed, BS: None Rafael De la Garza-Ramos, M.D: None C. Rory Goodwin, MD, PhD is a UNCF Merck Postdoctoral Fellow and has received an award from the Burroughs Welcome Fund and the Johns Hopkins Neurosurgery Pain Research Institute. Ziya L. Gokaslan, MD: Stock ownership in US Spine and Spinal Kinetics, consulting, speaking and teaching for the AO Foundation and Research support from Depuy, NREF, AOSpine and AO North America. Justin Sacks, MD: Consulting relationship with LifeCell. Daniel M. Sciubba, MD has consulting relationships with Medtronic, Globus, DePuy, and Stryker.

[16]

[17]

[18]

[19]

[20]

[21]

Conflict of interest The manuscript submitted does not contain information about medical device(s)/drug(s). This research did not receive any specific grant from funding agencies in the public, commercial, or notfor-profit sectors. The authors have no conflicts of interest.

[22]

[23]

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Please cite this article in press as: Pedreira R et al. Hardware failure in patients with metastatic cancer to the spine. J Clin Neurosci (2017), http://dx.doi. org/10.1016/j.jocn.2017.05.038