Hybrid Therapy (Surgery and Radiosurgery) for the Treatment of Renal Cell Carcinoma Spinal Metastases

BACKGROUND:

The management of spinal metastatic renal cell carcinoma (mRCC) is controversial regarding extent of resection and radiation dosing.

OBJECTIVE:

To determine outcomes in patients treated with hybrid therapy (separation surgery plus adjuvant stereotactic body radiation therapy [SBRT]) for mRCC.

METHODS:

A retrospective study of a prospectively collected cohort of patients undergoing hybrid therapy for mRCC between 2003 and 2017 was performed. SBRT was delivered as high-dose single-fraction, high-dose hypofractionated, or low-dose hypofractionated. Extent of disease, clinical and operative outcomes, and complications data were collected, and associations with overall survival (OS) and progression-free survival were determined.

RESULTS:

Ninety patients with mRCC with high-grade epidural spinal cord compression (ESCC grades 2 and 3) were treated. Metastases were widespread, oligometastatic, and solitary in 56%, 33%, and 11% of patients, respectively. SBRT delivered was high-dose single-fraction, high-dose hypofractionated, and low-dose hypofractionated in 24%, 56%, and 20% of patients, respectively. The 1-yr cumulative incidence of major complications was 3.4% (95% confidence interval [CI]: 0.0%-7.2%). The median follow-up was 14.2 mo for the entire cohort and 38.3 mo for survivors. The 1-yr cumulative incidence of progression was 4.6% (95% CI: 0.2%-9.0%), which translates to a local control rate of 95.4% (95% CI: 91.0%-99.8%) 1 yr after surgery. The median OS for the cohort was 14.8 mo.

CONCLUSION:

These data support the use of hybrid therapy as a safe and effective strategy for the treatment of renal cell spine metastases.

ABBREVIATIONS:

cEBRT

conventional external beam radiation therapy

DOS

date of surgery

ECOG

Eastern Cooperative Oncology Group

ESCC

epidural spinal cord compression

LC

local control

mRCC

metastatic renal cell carcinoma

OS

overall survival

POD

progression of disease

PORT

postoperative radiation therapy

RCC

renal cell carcinoma

SBRT

stereotactic body radiation therapy

SMD

spinal metastatic disease.

Renal cell carcinoma (RCC) is responsible for nearly 15 000 deaths annually in the United States.¹ Over the past 30 years, the incidence of RCC has increased, partly due to the increased frequency of imaging allowing for early detection.² Advances in immunotherapy and biologicals have profoundly affected prognosis for RCC, although the overall 5-yr survival rate remains poor.^3-8

RCC metastases develop in approximately 35% of patients, with 15% presenting with synchronous disease at the time of diagnosis and 20% with metachronous disease developing over the course of their illness.⁹ Bone is a common target for metastatic RCC (mRCC), seen in 30% of patients, of which 30% present with symptomatic tumors in the spine.^10-12 Despite tremendous promise regarding disease control, mRCC to the spine has consistently demonstrated poor responses to systemic therapies.^7,13 However, the effective treatment and long-term outcomes of mRCC to the spine have improved dramatically with the integration of stereotactic body radiotherapy (SBRT)^3,5,7,8,14 into treatment paradigms.

Historically, patients with spinal mRCC have been treated with en bloc resections to achieve wide margins. These procedures carry significant morbidity,^15-19 and the utility in the metastatic population has long been questioned. Radiotherapy now plays a critical role in the multimodal approach to metastatic spinal lesions.^20,21 RCC is among the subtype of cancers recognized as relatively resistant to conventional external beam radiation therapy (cEBRT).^22,23 Conversely, SBRT, in which ablative doses of highly conformal radiation are delivered in 1 to 5 fractions, has demonstrated improved local tumor control compared with cEBRT.¹⁴ However, in cases of high-grade spinal cord compression, the ability to safely deliver SBRT is limited by spinal cord dose constraints. Furthermore, underdosing the tumor because of concerns for spinal cord toxicity has led to high rates of tumor progression or recurrence in the epidural space.²⁴ This concern led to the development of hybrid therapy, consisting of separation surgery followed by SBRT.²⁵ This therapy is gaining wide acceptance for radioresistant spine metastases with studies demonstrating >90% local disease control and improved patient-reported outcomes.^26-28 In this study, we analyzed patients presenting with high-grade epidural spinal cord compression (ESCC) from mRCC who have undergone hybrid therapy to assess tumor control, clinical outcomes, and morbidity.

METHODS

A retrospective study of a prospectively collected cohort of patients with high-grade ESCC (grades 2 and 3)²⁹ undergoing hybrid therapy for pathology-proven spinal mRCC at a single tertiary institution between 2003 and 2017 was performed (Figure 1). Institutional review board approval and informed consent were obtained. Patients with previous surgery at the index level, those who underwent percutaneous stabilization procedures without decompression and biopsies, and those who received conventional radiation postoperatively were excluded.

FIGURE 1.

Representative case example of mRCC to the spine. Preoperative A, sagittal T1-weighted and B, axial T1-weighted postcontrast magnetic resonance imaging of a 64-yr-old woman with mRCC. She presented to the emergency department with severe movement-related back pain but no neurological deficit. A magnetic resonance imaging examination demonstrated involvement of the L1 vertebrae with epidural spinal cord compression. The patient underwent hybrid therapy involving separation surgery of the L1 metastasis with instrumented stabilization from T11-L3. C, Axial computed tomography myelogram image demonstrates reconstitution of the thecal sac immediately after surgery. D, Stereotactic body radiation therapy plan involved 9 Gy in 3 fractions delivered in a conformal pattern to maximize dosage to the remaining tumor volume within the vertebral body and pedicles while minimizing dosage to the spinal cord and surrounding non-neoplastic soft and visceral tissues. Four years after hybrid therapy, E, anteroposterior x-ray demonstrated preservation of coronal alignment without evidence of hardware failure. F, Sagittal and G, axial T2-weighted images demonstrated no epidural disease compressing the thecal sac at the L1 level with preservation of the cauda equina nerve roots. H, Sagittal perfusion MRI demonstrates the lack of avid metabolic uptake in the region of the L1 lesion substantiating local control. At the time of this follow-up imaging, the patient remained fully ambulatory and pain free without any neurological deficit. mRCC, metastatic renal cell carcinoma.

Nuances of surgical indications, procedural details, and radiation planning are described in Text, Supplemental Digital Content 1, http://links.lww.com/NEU/A942.

In brief, the indications for surgery were determined using the neurological/oncological/mechanical/systemical paradigm.³⁰ A posterior-only laminectomy and transpedicular approach for circumferential decompression of the neural elements and instrumented stabilization was performed. Patients with anterior vertebral body disease underwent a partial vertebrectomy and resection of the posterior longitudinal ligament. Anterior polymethyl methacrylate reconstruction was routinely used in patients with greater than 50% resection of the vertebral body. No patient underwent en bloc resection.

Over the course of the study, the 3-dose strategies used were stratified by the radiation oncologists based on comparable computed biological equivalent doses as high-dose single fraction (24 Gy), high-dose hypofractionated (9-10 Gy in 3 fractions or 18 Gy in a single fraction), or low-dose hypofractionated (8 Gy in 3 fractions or 6-7 Gy in 5 fractions).

Baseline patient demographic, perioperative, and radiation therapy data were collected. The extent of systemic disease at time of surgery was divided into solitary metastases, oligometastases (ie, 2-5 tumors), or widespread metastases (>5 tumors). Complications were divided into those less or greater than 30 d postoperatively and also as major vs minor. Major complications were defined as those requiring invasive measures or resulting in permanent disability or death.

Statistical Analysis

The associations between variables of interest with overall survival (OS) were investigated with Cox proportional hazards regression modeling. Cumulative incidence and 95% confidence intervals (CIs) were estimated for progression in the competing risks setting where the competing event was death. Cumulative incidence was calculated from date of surgery until progression (event of interest), death (competing event), or last follow-up (censored). Analogous cumulative incidence estimation was performed for complications postoperatively. All tests were 2-sided with an alpha level of statistical significance set at less than 0.05. Additional analyses are described in Text, Supplemental Digital Content 1, http://links.lww.com/NEU/A942.

RESULTS

Patient and Treatment Characteristics

A total of 208 patients were screened of which 90 met inclusion criteria. Baseline and intraoperative variables are summarized in Table 1. The Eastern Cooperative Oncology Group (ECOG) score was used to assess patient function. At baseline, 6 (7%), 50 (55%), and 28 (31%) patients were ECOG 0, 1, and 2, respectively. Six patients were ECOG 3 or 4 (7%). The median time between surgery and postoperative radiation therapy was 25 d (12-134 d). Twenty-two patients (24.4%) received single-fraction SRS, 50 (55.6%) received high-dose hypofractionated SBRT, and 18 (20%) received low-dose hypofractionated SBRT (Table 2). There was no statistically significant difference in median total radiation dose given between patients with solitary lesions, oligometastases, and widespread disease (Table, Supplemental Digital Content 2, http://links.lww.com/NEU/A943).

TABLE 1.

Patient Characteristics

Characteristic	N (%) or median (range)
Sex
Male	75 (83)
Female	15 (17)
Age at surgery (yr)	62.1 (35.6-84.5)
Preoperative ECOG performance status
0	6 (7)
1	50 (55)
2	28 (31)
3	5 (6)
4	1 (1)
Previous RT at index level
Yes	20 (22)
No	70 (78)
Median previous RT dose, Gy	28.5 (18-37.5)
Degree of systemic diseasea
Solitary metastasis	10 (11)
Oligometastatic disease	30 (33)
Widespread disease	50 (56)
Index treatment level(s)
Cervical	8 (9)
Cervicothoracic	2 (2)
Thoracic	52 (58)
Thoracolumbar	2 (2)
Lumbar	26 (29)

ECOG, Eastern Cooperative Oncology Group; RT, radiation therapy.

^aOligometastatic disease defined as 2-5 total metastatic lesions, regardless of site. Widespread disease defined as >5 metastatic lesions regardless of site.

TABLE 2.

Operative and Radiation Details

Characteristic	N (%) or median (range)
Preoperative embolization
Yes	72 (80)
No	18 (20)
Operative time, min	162 (89-495)
Estimated blood loss, mL	1000 (100-6800)
Number of levels decompressed	3 (1-6)
Number of levels instrumentation	5 (3-10)
Days to postoperative RT	25 (12-134)
Radiation treatment
SRS (24 Gy in 1 fraction)	22 (24.4)
High-dose SBRT	50 (55.6)
18 Gy in 1 fraction	2 (2.2)
9 Gy in 3 fractions	44 (48.9)
9.5 Gy in 3 fractions	2 (2.2)
10 Gy in 3 fractions	2 (2.2)
Low-dose SBRT	18 (20)
8 Gy in 3 fractions	4 (4.4)
6 Gy in 5 fractions	10 (4.4)
7 Gy in 5 fractions	4 (4.4)
Postoperative RT total dose, Gy	27 (18-35)
Postoperative RT Biological effective dose, Gy	51.3 (43.2-81.6)

RT, radiation therapy; SBRT, stereotactic body radiation therapy.

Complications

Sixteen patients (18%) had complications related to either surgery or radiation, of which 11 (12.2%) were major requiring a subsequent procedure during the course of the study. The 1-yr and 2-yr cumulative incidences of major complications were 3.4% (95% CI: 0.0%-7.2%) and 9.3% (95% CI: 3.1%-15.6%), respectively. The major complications were hardware failure (7.7%), deep wound infection or dehiscence (3.3%), and esophageal perforation 1 (1.1%) (Text, Supplemental Digital Content 1, http://links.lww.com/NEU/A942 and Table, Supplemental Digital Content 3, http://links.lww.com/NEU/A944). The 4 minor complications included superficial wound infection (1.1%), deep venous thrombosis (DVT) (2.2%), radiation-induced myositis (1.1%), and pneumonitis (1.1%). With the exception of the superficial wound infection and both DVTs, which occurred in the perioperative period, most of the complications occurred >30 d from surgery (Table 3).

TABLE 3.

Surgical and Radiation-Related Complications

Characteristic	N (%)
Total	16 (18)
Major	11 (12)
Minor	5 (6)
Within 30 d	3 (19)
>30 d	13 (81)
Major complications
Hardware complication	7
Deep wound infection/breakdown	3
Esophageal perforationa	1
Minor complications
Superficial wound infection	1
DVT	2
Myositisa	1
Pneumonitisa	1

DVT, deep venous thrombosis.

^aRadiation-related complications.

OS and Progression-Free Survival

The median follow-up time for the cohort was 14.2 mo. The median OS for the entire cohort was 14.8 mo (95% CI: 11.5-30.0). At the conclusion of the study, 22 patients (24.4%) were still alive and 68 (75.6%) had died. For patients still alive, the median time to last follow-up was 38.3 mo. For patients who died, the median time to death was 11.5 mo. The 1-yr and 2-yr incidences of progression were 4.6% (95% CI: 0.2%-9.0) and 8.2% (95% CI: 2.3%-14.1%), respectively (Table 4). This translates to cumulative local control (LC) rates of 95.4% and 91.8% at 1 yr and 2 yr after surgery, respectively (Figure 2). Of the 7 patients who demonstrated local progression of disease (POD), the median time to POD requiring treatment was 13.9 mo (3.9-23.4 mo). There were 3 patients who had marginal paraspinal progression that did not require additional treatment to the index level and therefore were not included as progression of disease. At the 6-mo follow-up, 31% of patients died, with 61% of surviving patients demonstrating ECOG performance scores ranging from 0 to 2 (Table 4). There was no statistically significant association between any baseline or operative variable with OS or progression-free survival (PFS) (Tables, Supplemental Digital Content 4, http://links.lww.com/NEU/A945 and 5, http://links.lww.com/NEU/A946).

TABLE 4.

Clinical Outcomes

Characteristic	N (%) or median (range)a
Hospital length of stay, d	5 (3-27)
Vital statusb
Alive	22 (24.4)
Dead	68 (75.6)
Progression (overall)
No	83 (92.2)
Yes	7 (7.8)
Cumulative incidence of progression
1 yr after surgery	4.6% (95% CI: 0.2%-9.0%)
2 yr after surgery	8.2% (95% CI: 2.3%-14.1%)
Median time to progression (mo)	13.9 (3.9-23.4)
Management of progression
Surgery + PORT	5
RT alone	2
Median follow-up from date of surgery (mo)
Total	14.2 (1.3-86.3)
Alive	38.3 (1.9-86.3)
Deceased	11.5 (1.3-76.1)
Overall survival from date of surgery, median and 95% CI (mo)	14.8 (11.5-30.0)
Discharge destination
Home	78 (87)
Rehabilitation	12 (13)
ECOG performance status at 6 mo postoperatively
0	10 (11)
1	29 (32)
2	16 (18)
3	1 (1)
4	0 (0)
5 (dead)	28 (31)
Unknown	6 (7)
ECOG 12 mo postoperatively
0	11 (12)
1	22 (24)
2	7 (8)
3	4 (4)
4	0 (0)
5 (deceased)	40 (44)
Unknown	6 (7)

ECOG, Eastern Cooperative Oncology Group; CI, confidence interval; PORT, postoperative radiation therapy.

^aUnless otherwise specified.

^bVital status at the end of study period.

FIGURE 2.

Kaplan–Meier curve demonstrating A, overall survival and B, progression-free survival from DOS. C, Cumulative incidence curve of cases that demonstrated progression of disease. DOS, date of surgery.

Upfront vs Salvage Therapy

A subgroup analysis comparing patients who underwent upfront hybrid therapy with those who received salvage treatment was performed. Twenty patients (22%) had previous RT at the index level, with a mean initial dose of 28.5 Gy (range 18-37.5 Gy). Of the most regimens used by outside institutions, 8 patients received 30 Gy in 10 fractions (ie, conventional radiation) and 4 patients received 27 Gy in 3 fractions. The median time from the completion of initial RT to surgery at our institution was 12.5 months (0.1-60.3 mo). All these patients undergoing salvage therapy received either low-dose hypofractionated (60%) or high-dose hypofractionated SBRT (40%). Of the 70 RT-naive patients, 31% received single-fraction SRS and 60% received high-dose hypofractionated SBRT. Of the 7 patients who demonstrated POD, 4 were in the upfront group, of which 3 received additional RT (30 Gy in 5 fractions, 35 Gy in 5 fractions, and 27 Gy in 3 fractions). The complication risk between the salvage and upfront groups was 10% and 20%, which was not statistically significant.

DISCUSSION

Key Results and Interpretation

To the best of our knowledge, these data represent the largest series of symptomatic mRCC with high-grade ESCC treated with separation surgery combined with SBRT. This hybrid therapy demonstrates a cumulative LC rate of 95.4% and 91.8% at 1 yr and 2 yr after surgery, respectively (Figure 2). The median time to progression was 14.1 mo. Sixty-one percentage of patients had ECOG performance scores ranging from 0 to 2 at the 6-mo follow-up. The 2-yr cumulative postoperative major complication rate was 9.3%.

SBRT is a well-established treatment for mRCC to the spine with minimal or no ESCC as stand-alone therapy.²⁹ Sohn et al³¹ found PFS rates of SRS vs cEBRT for mRCC to be 86% and 29%, respectively. Thibualt et al³² demonstrated 1-yr LC rates for RCC spinal metastases of 83% using a dose fractionation scheme of 12 Gy × 2 fractions. The median time to local recurrence was 11.5 mo. Ghia et al³³ demonstrated median overall 1-yr LC rates for mRCC of 82%; however, they noted that single-fraction SRS (24 Gy) was significantly better than multifraction regimens (95% vs 71% LC rates). A systematic review of SBRT for RCC spinal metastases demonstrated 1-yr LC rates ranging from 71.2% to 85.7%.³⁴ Blakaj et al³⁵ recently demonstrated that LC of metastatic spine tumors was improved if radiosurgery was performed within 40 d of surgery compared with that after 40 d from surgery, with 1-yr LC rates of 94% vs 75%, respectively (P = .03). The median days from surgery to RT was 25 d in our group. Outliers in our cohort were due to postoperative complications that required stabilization before further treatment (Text, Supplemental Digital Content 1, http://links.lww.com/NEU/A942). Moreover, 18-Gy single-fraction treatment was classified to the high-dose hypofractionated group in our study because of statistically significantly worse local tumor control rates compared with high-dose single-fractionated regimens (ie, 21-24 Gy) in previous studies.^36,37 Thus, we differentiated these 2 single-fraction regimens.

Several reports of outcomes for mRCC cohorts with greater than 30 patients (489 patients in total) who underwent surgery for mRCC have been published,^38-42 but with limited adjuvant radiation data. Tatsui et al⁴¹ reported 267 consecutive patients undergoing surgery for mRCC, but SRS was not available for most patients postoperatively. The median OS was 11.3 mo, and Furhman grade 4 tumors, postoperative neurological deficits, widespread extraspinal metastases, and cervical spine involvement were poor prognostic factors for survival. PFS was 85%, and the complication rate was 13%. Shankar et al⁴² identified 78 patients with spinal mRCC of which only 41% of patients underwent postoperative RT. Notably, their study captured the effect of currently available postoperative systemic therapies that increased OS by 913 d (n = 49) compared with 222 d (n = 29) in those who did not. PFS, however, was not significantly affected by adjuvant radiation or systemic therapy. The median PFS and OS were 179 d and 717 d, respectively. Eight patients (10.3%) experienced complications in this cohort.

More aggressive surgical strategies, including en bloc resection of solitary spinal mRCC, have been advocated by some groups. However, this technique is associated with high rates of complications (41.7%-46.2%) and 1.9% to 4.6% risk of surgical-related mortality.⁴³ In our cohort, which included those with a solitary metastasis, the total complication rate was 18% with hybrid surgery, most commonly due to hardware failure or wound complications with no permanent neurological deficits. A criticism of separation surgery is that the lack of anterior column reconstruction places patients at higher risk of developing hardware/fixation failure. Cement augmentation of fenestrated pedicles screws or concomitant vertebroplasty of affected vertebral bodies are strategies that have been used to mitigate this risk.^44-46 However, without a long-term study, the rate of fixation failure cannot be adequately studied.

Upfront vs Salvage Therapy

Seventy patients in our series underwent hybrid therapy as their primary intervention. Of them, 31% received high-dose single-fraction SRS and 60% received high-dose hypofractionated SBRT. As a postoperative adjuvant, high-dose hypofractionated SBRT is routinely used over high-dose single-fraction SRS to improve the therapeutic window in tumors when clinical conditions will not allow normal tissue dose constraints, such as when the allowable dose to spinal cord and other critical organs cannot be met. For example, high-dose hypofractionated SBRT was used in the case of multilevel vertebral body involvement, large paraspinal masses, previous radiation, and/or close spinal cord margins (eg, ESCC 1c). The decision to use low-dose vs high-dose hypofractionated SBRT for upfront or recurrence treatment is wholly reflective of practice pattern changes over time. High-dose hypofractionated radiation has replaced low-dose regimens because they have demonstrated improved local tumor control without inducing spinal cord toxicity.²⁵ Gerzten et al⁴⁷ followed up patients with RCC spinal metastases retreated with single-fraction SRS and a mean dose of 20 Gy at a mean follow-up of 37 mo. In their study, 88% of patients treated for increase in tumor size on imaging demonstrated LC during the study period with no toxicities reported despite 70% of patients being previously treated with cEBRT. Collectively these findings support the use of SBRT because of the ability to strictly limit the maximum dose to the spinal cord, but not tumor volume as afforded by modern planning systems.

No baseline or perioperative variables (surgical and radiation-related) demonstrated statistically significant associations with OS or PFS. Previous reports demonstrate worse prognosis for patients with increasing number of metastatic spinal tumors^48,49 or presence of a preoperative neurological deficit on prognosis.^{39,41,48,50,51} The importance and independent impact of the extent of the local disease treated and baseline neurological status on overall prognosis is unclear but warrants further study.

In summary, combinatorial strategy between spine surgeons and radiation oncologists for delivering hybrid surgery in the setting of broader multidisciplinary mRCC management is a safe and effective treatment strategy. This treatment paradigm can be performed with low morbidity and acceptable LC and even as a salvage procedure in those who have been previously irradiated. Further long-term survival analyses and head-to-head comparison with more aggressive surgical intervention strategies are required to adequately demonstrate the effectiveness of this approach.

Limitations

There are a number of limitations of our study. First, given the retrospective design, no aspects of care were randomized. Second, data collection did not include chemotherapy/immunotherapeutic treatments before or after surgery. This limits our ability to interpret the impact chemotherapy/immunotherapy may play in the development of operative mRCC to the spine and outcomes beyond hybrid surgery. Third, patients at our institution do not undergo en bloc resection of solitary metastases; therefore, there was no comparison group for analysis. Fourth, survival bias may be influencing our outcomes because we cannot surmise if burden of disease from mRCC contributed to death or if POD was present at the time of death. Fifth, we did not collect data pertaining to pain improvement or quality of life measures, which would aid in determining further benefits of hybrid therapy.

CONCLUSION

Hybrid spinal surgery for mRCC resulting in high-grade spinal cord compression demonstrates a high rate of LC and low major complication risk. This approach is effective regardless of previous radiation or degree of systemic disease. Further studies are required to understand the multivariable influence of systemic therapies on hybrid surgery for mRCC.

Funding

This work was funded by NIH/NCI Cancer Center (Grant No. P30 CA008748).

Disclosures

The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. Dr Laufer receives consulting fees from DePuy/Synthes, Globus, Spine Wave, and Medtronic. Dr Bilsky receives consulting fees from Varian and Stryker and royalties from Globus and DePuy/Synthes.

COMMENT

The authors are commended for a well-written manuscript describing outcomes for patients with renal cell carcinoma (RCC) undergoing separation surgery followed by stereotactic body radiation therapy (SBRT) for spinal metastases. This is a particularly timely article as major advances have been made in the systemic control of RCC using targeted therapy. There are expanded surgical indications for RCC spinal metastatic disease (SMD) patients due to improved overall survival in this patient population.

A standard, repeatable separation surgery operative approach to most patients with SMD can be used to achieve decompression and stabilization. Separation surgery can offer advantages over en bloc resection, including shorter operative time and familiar anatomical positioning, and obviate the need for an exposure surgeon. A caveat of separation surgery is that without removing the entire tumor, hemostasis can be challenging as residual tumor does not clot when compared with healthy tissue. This is a particular concern in highly vascular RCC tumors, and thus, preoperative embolization is recommended when feasible.

While operative techniques are most interesting to the neurosurgeon, it is most likely that advances in spinal SBRT resulted in the improved local control (LC) rates reported in this study. Even in cases of en bloc resection, residual microscopic disease often remains when removing metastatic tumor, and gross residual disease may occur. Whether en bloc surgical resection or separation surgery is performed, the postoperative radiotherapy and systemic therapy will have a major impact on long-term LC. This study supports a comprehensive Spinal Oncology Program for SMD patients.

Andrew J. Fabiano

Buffalo, NY, USA

Supplemental Digital Content

Supplemental Digital Content 1. Text. Expanded methods and results.

Supplemental Digital Content 2. Table. Association between degree of systemic disease and postoperative RT dose.

Supplemental Digital Content 3. Table. Hardware failure cases.

Supplemental Digital Content 4. Table. Association between baseline and operative variables with OS and PFS from date of surgery.

Supplemental Digital Content 5. Table. Association between RT variables with OS and PFS from date of PORT.