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Chunzi Jenny Jin, John Berry-Candelario, Anne S. Reiner, Ilya Laufer, Daniel S. Higginson, Adam M. Schmitt, Eric Lis, Ori Barzilai, Patrick Boland, Yoshiya Yamada and Mark H. Bilsky

OBJECTIVE

The current treatment of chordomas is associated with significant morbidity, high rates of local recurrence, and the potential for metastases. Stereotactic radiosurgery (SRS) as a primary treatment could reduce the need for en bloc resection to achieve wide or marginal margins. Spinal SRS outcomes support the exploration of SRS’s role in the durable control of these conventionally radioresistant tumors. The goal of the study was to evaluate outcomes of patients with primary chordomas treated with spinal SRS alone or in combination with surgery.

METHODS

Clinical records were reviewed for outcomes of patients with primary chordomas of the mobile spine and sacrum who underwent single-fraction SRS between 2006 and 2017. Radiographic local recurrence-free survival (LRFS), overall survival (OS), symptom response, and toxicity were assessed in relation to the extent of surgery.

RESULTS

In total, 35 patients with de novo chordomas of the mobile spine (n = 17) and sacrum (n = 18) received SRS and had a median post-SRS follow-up duration of 38.8 months (range 2.0–122.9 months). The median planning target volume dose was a 24-Gy single fraction (range 18–24 Gy). Overall, 12 patients (34%) underwent definitive SRS and 23 patients (66%) underwent surgery and either neoadjuvant or postoperative adjuvant SRS. Definitive SRS was selectively used to treat both sacral (n = 7) and mobile spine (n = 5) chordomas. Surgical strategies for the mobile spine were either intralesional, gross-total resection (n = 5) or separation surgery (n = 7) and for the sacrum en bloc sacrectomy (n = 11). The 3- and 5-year LRFS rates were 86.2% and 80.5%, respectively. Among 32 patients (91%) receiving 24-Gy radiation doses, the 3- and 5-year LRFS rates were 96.3% and 89.9%, respectively. The 3- and 5-year OS rates were 90.0% and 84.3%, respectively. The symptom response rate to treatment was 88% for pain and radiculopathy. The extent or type of surgery was not associated with LRFS, OS, or symptom response rates (p > 0.05), but en bloc resection was associated with higher surgical toxicity, as measured using the Common Terminology Criteria for Adverse Events (version 5.0) classification tool, than epidural decompression and curettage/intralesional resection (p = 0.03). The long-term rate of toxicity ≥ grade 2 was 31%, including 20% grade 3 tissue necrosis, recurrent laryngeal nerve palsy, myelopathy, fracture, and secondary malignancy.

CONCLUSIONS

High-dose spinal SRS offers the chance for durable radiological control and effective symptom relief with acceptable toxicity in patients with primary chordomas as either a definitive or adjuvant therapy.

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Ori Barzilai, Lily McLaughlin, Eric Lis, Yoshiya Yamada, Mark H. Bilsky and Ilya Laufer

OBJECTIVE

As patients with metastatic cancer live longer, an increased emphasis is placed on long-term therapeutic outcomes. The current study evaluates outcomes of long-term cancer survivors following surgery for spinal metastases.

METHODS

The study population included patients surgically treated at a tertiary cancer center between January 2010 and December 2015 who survived at least 24 months postoperatively. A retrospective chart and imaging review was performed to collect data regarding patient demographics; tumor histology; type and extent of spinal intervention; radiation data, including treatment dose and field; long-term sequelae, including local tumor control; and reoperations, repeat irradiation, or postoperative kyphoplasty at a previously treated level.

RESULTS

Eighty-eight patients were identified, of whom 44 were male, with a mean age of 61 years. The mean clinical follow-up for the cohort was 44.6 months (range 24.2–88.3 months). Open posterolateral decompression and stabilization was performed in 67 patients and percutaneous minimally invasive surgery in 21. In the total cohort, 84% received postoperative adjuvant radiation and 27% were operated on for progression following radiation. Posttreatment local tumor progression was identified in 10 patients (11%) at the index treatment level and 5 additional patients had a marginal failure; all of these patients were treated with repeat irradiation with 5 patients requiring a reoperation. In total, at least 1 additional surgical intervention was performed at the index level in 20 (23%) of the 88 patients: 11 for hardware failure, 5 for progression of disease, 3 for wound complications, and 1 for postoperative hematoma. Most reoperations (85%) were delayed at more than 3 months from the index surgery. Wound infections or dehiscence requiring additional surgical intervention occurred in 3 patients, all of which occurred more than a year postoperatively. Kyphoplasty at a previously operated level was performed in 3 cases due to progressive fractures.

CONCLUSIONS

Durable tumor control can be achieved in long-term cancer survivors surgically treated for symptomatic spinal metastases with limited complications. Complications observed after long-term follow-up include local tumor recurrence/progression, marginal tumor control failures, early or late hardware complications, late wound complications, and progressive spinal instability or deformity.

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Ibrahim Hussain, Ori Barzilai, Anne S. Reiner, Lily McLaughlin, Natalie M. DiStefano, Shahiba Ogilvie, Anne L. Versteeg, Charles G. Fisher, Mark H. Bilsky and Ilya Laufer

OBJECTIVE

The Spinal Instability Neoplastic Score (SINS) correlates with preoperative disability and response to stabilization, with patients with higher scores experiencing greater relief after surgery. However, there is a paucity of data demonstrating the extent to which each component contributes to preoperative clinical status and response to stabilization surgery. The objectives of this study were 2-fold. First, to determine how SINS components correlate with pre- and postoperative patient-reported outcomes (PROs). Second, to determine whether patients with higher SINS (10–12) in the “indeterminate” group respond differently to surgery compared to patients with lower SINS (7–9).

METHODS

SINS and PROs were prospectively collected in 131 patients undergoing stabilization surgery for metastatic spinal disease. Association of SINS components and their individual scores with preoperative symptom burden and PRO symptom change after surgery was analyzed using the Spearman rank correlation coefficient (rho) and the Kruskal-Wallis test. SINS and association with preoperative PRO scores and mean differences in post- and preoperative PRO scores were compared for 2 SINS categories within the indeterminate group (7–9 vs 10–12) using the Wilcoxon 2-sample test and Wilcoxon signed-rank test.

RESULTS

The presence of mechanical pain, followed by metastatic location, correlated most strongly with preoperative functional disability measures and lower disability PRO scores following surgical stabilization. Blastic rather than lytic bone lesions demonstrated stronger association with pain reduction following stabilization. Following surgery, patients with SINS 10–12 demonstrated markedly greater improvement in pain and disability PRO scores nearly across the board compared to patients with SINS 7–9.

CONCLUSIONS

The presence of mechanical pain has the strongest correlation with preoperative disability and improvement in pain and disability PRO scores after surgery. Radiographic components of SINS also correlate with preoperative symptom severity and postoperative PRO, supporting their utilization in evaluation of spinal instability. Among patients with indeterminate SINS, patients with higher scores experience greater reduction in pain and disability PRO scores following surgical stabilization, suggesting that the indeterminate-SINS group includes distinct populations.

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Eric Lis, Ilya Laufer, Ori Barzilai, Yoshiya Yamada, Sasan Karimi, Lily McLaughlin, George Krol and Mark H. Bilsky

OBJECTIVE

Percutaneous vertebral augmentation procedures such as vertebroplasty and kyphoplasty are often performed in cancer patients to relieve mechanical axial-load pain due to pathological collapse deformities. The collapsed vertebrae in these patients can be associated with varying degrees of spinal canal compromise that can be worsened by kyphoplasty. In this study the authors evaluated changes to the spinal canal, in particular the cross-sectional area of the thecal sac, following balloon kyphoplasty (BKP) prior to stereotactic radiosurgery (SRS).

METHODS

The authors retrospectively reviewed the records of all patients with symptomatic vertebral compression fractures caused by metastatic disease who underwent kyphoplasty prior to single-fraction SRS. The pre-BKP cross-sectional image, usually MRI, was compared to the post-BKP CT myelogram required for radiation treatment planning. The cross-sectional area of the thecal sac was calculated pre- and postkyphoplasty, and intraprocedural CT imaging was reviewed for epidural displacement of bone fragments, tumor, or polymethylmethacrylate (PMMA) extravasation. The postkyphoplasty imaging was also evaluated for evidence of fracture progression or fracture reduction.

RESULTS

Among 30 consecutive patients, 41 vertebral levels were treated with kyphoplasty, and 24% (10/41) of the augmented levels showed a decreased cross-sectional area of the thecal sac. All 10 of these vertebral levels had preexisting epidural disease and destruction of the posterior vertebral body cortex. No bone fragments were displaced posteriorly. Minor epidural PMMA extravasation occurred in 20% (8/41) of the augmented levels but was present in only 1 of the 10 vertebral segments that showed a decreased cross-sectional area of the thecal sac postkyphoplasty.

CONCLUSIONS

In patients with preexisting epidural disease and destruction of the posterior vertebral body cortex who are undergoing BKP for pathological fractures, there is an increased risk of further mass effect upon the thecal sac and the potential to alter the SRS treatment planning.

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Ori Barzilai, Shlomit Ben Moshe, Razi Sitt, Gal Sela, Ben Shofty and Zvi Ram

OBJECTIVE

Cognition is a key component in health-related quality of life (HRQoL) and is currently incorporated as a major parameter of outcome assessment in patients treated for brain tumors. The effect of surgery on cognition and HRQoL remains debatable. The authors investigated the impact of resection of low-grade gliomas (LGGs) on cognition and the correlation with various histopathological markers.

METHODS

A retrospective analysis of patients with LGG who underwent craniotomy for tumor resection at a single institution between 2010 and 2014 was conducted. Of 192 who underwent resective surgery for LGG during this period, 49 had complete pre- and postoperative neurocognitive evaluations and were included in the analysis. These patients completed a full battery of neurocognitive tests (memory, language, attention and working memory, visuomotor organization, and executive functions) pre- and postoperatively. Tumor and surgical characteristics were analyzed, including volumetric measurements and histopathological markers (IDH, p53, GFAP).

RESULTS

Postoperatively, significant improvement was found in memory and executive functions. A subgroup analysis of patients with dominant-side tumors, most of whom underwent intraoperative awake mapping, revealed significant improvement in the same domains. Patients whose tumors were on the nondominant side displayed significant improvement only in memory functions. Positive staining for p53 testing was associated with improved language function and greater extent of resection in dominant-side tumors. GFAP positivity was associated with improved memory in patients whose tumors were on the nondominant side. No correlation was found between cognitive outcome and preoperative tumor volume, residual volume, extent of resection, or IDH1 status.

CONCLUSIONS

Resection of LGG significantly improves memory and executive function and thus is likely to improve functional outcome in addition to providing oncological benefit. GFAP and pP53 positivity could possibly be associated with improved cognitive outcome. These data support early, aggressive, surgical treatment of LGG.

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Ori Barzilai, Natalie DiStefano, Eric Lis, Yoshiya Yamada, D. Michael Lovelock, Andrew N. Fontanella, Mark H. Bilsky and Ilya Laufer

OBJECTIVE

The aim of this study was to evaluate the safety and efficacy of kyphoplasty treatment prior to spine stereotactic radiosurgery (SRS) in patients with spine metastases.

METHODS

A retrospective review of charts, radiology reports, and images was performed for all patients who received SRS (single fraction; either standalone or post-kyphoplasty) at a large tertiary cancer center between January 2012 and July 2015. Patient and tumor variables were documented, as well as treatment planning data and dosimetry. To measure the photon scatter due to polymethyl methacrylate, megavolt photon beam attenuation was determined experimentally as it passed through a kyphoplasty cement phantom. Corrected electron density values were recalculated and compared with uncorrected values.

RESULTS

Of 192 treatment levels in 164 unique patients who underwent single-fraction SRS, 17 (8.8%) were treated with kyphoplasty prior to radiation delivery to the index level. The median time from kyphoplasty to SRS was 22 days. Four of 192 treatments (2%) demonstrated local tumor recurrence or progression at the time of analysis. Of the 4 local failures, 1 patient had kyphoplasty prior to SRS. This recurrence occurred 18 months after SRS in the setting of widespread systemic disease and spinal tumor progression. Dosimetric review demonstrated a lower than average treatment dose for this case compared with the rest of the cohort. There were no significant differences in dosimetry analysis between the group of patients who underwent kyphoplasty prior to SRS and the remaining patients in the cohort. A preliminary analysis of polymethyl methacrylate showed that dosimetric errors due to uncorrected electron density values were insignificant.

CONCLUSIONS

In cases without epidural spinal cord compression, stabilization with cement augmentation prior to SRS is safe and does not alter the efficacy of the radiation or preclude physicians from adhering to SRS planning and contouring guidelines.

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Ori Barzilai, Zvi Lidar, Shlomi Constantini, Khalil Salame, Yifat Bitan-Talmor and Akiva Korn

Intramedullary spinal cord tumors (IMSCTs) represent a rare entity, accounting for 4%–10% of all central nervous system tumors. Microsurgical resection of IMSCTs is currently considered the primary treatment modality. Intraoperative neurophysiological monitoring (IONM) has been shown to aid in maximizing tumor resection and minimizing neurological morbidity, consequently improving patient outcome. The gold standard for IONM to date is multimodality monitoring, consisting of both somatosensory evoked potentials, as well as muscle-based transcranial electric motor evoked potentials (tcMEPs). Monitoring of tcMEPs is optimal when combining transcranial electrically stimulated muscle tcMEPs with D-wave monitoring. Despite continuous monitoring of these modalities, when classic monitoring techniques are used, there can be an inherent delay in time between actual structural or vascular-based injury to the corticospinal tracts (CSTs) and its revelation. Often, tcMEP stimulation is precluded by the surgeon’s preference that the patient not twitch, especially at the most crucial times during resection. In addition, D-wave monitoring may require a few seconds of averaging until updating, and can be somewhat indiscriminate to laterality. Therefore, a method that will provide immediate information regarding the vulnerability of the CSTs is still needed.

The authors performed a retrospective series review of resection of IMSCTs using the tip of an ultrasonic aspirator for continuous proximity mapping of the motor fibers within the spinal cord, along with classic muscle-based tcMEP and D-wave monitoring.

The authors present their preliminary experience with 6 patients who underwent resection of an IMSCT using the tip of an ultrasonic aspirator for continuous proximity mapping of the motor fibers within the spinal cord, together with classic muscle-based tcMEP and D-wave monitoring. This fusion of technologies can potentially assist in optimizing resection while preserving neurological function in these challenging surgeries.

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Madeleine Sowash, Ori Barzilai, Sweena Kahn, Lily McLaughlin, Patrick Boland, Mark H. Bilsky and Ilya Laufer

OBJECTIVE

The objective of this study was to review clinical outcomes following resection of giant spinal schwannomas.

METHODS

The authors conducted a retrospective review of a case series of patients with giant spinal schwannomas at a tertiary cancer hospital.

RESULTS

Thirty-two patients with giant spinal schwannomas underwent surgery between September 1998 and May 2013. Tumor size ranged from 2.5 cm to 14.6 cm with a median size of 5.8 cm. There were 9 females (28.1%) and 23 males (71.9%), and the median age was 47 years (range 23–83 years). The median follow-up duration was 36.0 months (range 12.2–132.4 months). Three patients (9.4%) experienced recurrence and required further treatment. All recurrences developed following subtotal resection (STR) of cellular or melanotic schwannoma. There were 3 melanotic (9.4%) and 6 cellular (18.8%) schwannomas included in this study. Among these histological variants, a 33.3% recurrence rate was noted. In 1 case of melanotic schwannoma, malignant transformation occurred. No recurrence occurred following gross-total resection (GTR) or when a fibrous capsule remained due to its adherence to functional nerve roots.

CONCLUSIONS

Resection is the treatment of choice for symptomatic or growing giant schwannomas, frequently requiring anterior or combined approaches, with the goals of symptom relief and prevention of recurrence. In this series, tumors that underwent GTR, or where only capsule remained, did not recur. Only melanotic and cellular schwannomas that underwent STR recurred.

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Michael D. Stubblefield, Katarzyna Ibanez, Elyn R. Riedel, Ori Barzilai, Ilya Laufer, Eric Lis, Yoshiya Yamada and Mark H. Bilsky

OBJECTIVE

The object of this study was to determine the percentage of high-dose (1800–2600 cGy) single-fraction stereotactic radiosurgery (SF-SRS) treatments to the spine that result in peripheral nervous system (PNS) injury.

METHODS

All patients treated with SF-SRS for primary or metastatic spine tumors between January 2004 and May 2013 and referred to the Rehabilitation Medicine Service for evaluation and treatment of neuromuscular, musculoskeletal, or functional impairments or pain were retrospectively identified.

RESULTS

Five hundred fifty-seven SF-SRS treatments in 447 patients resulted in 14 PNS injuries in 13 patients. All injures resulted from SF-SRS delivered to the cervical or lumbosacral spine at 2400 cGy. The overall percentage of SF-SRS treatments resulting in PNS injury was 2.5%, increasing to 4.5% when the thoracic spine was excluded from analysis. The median time to symptom onset following SF-SRS was 10 months (range 4–32 months). The plexus (cervical, brachial, and/or lumbosacral) was affected clinically and/or electrophysiologically in 12 (86%) of 14 cases, the nerve root in 2 (14%) of 14, and both in 6 (43%) of 14 cases. All patients experienced pain and most (93%) developed weakness. Peripheral nervous system injuries were CTCAE Grade 1 in 14% of cases, 2 in 64%, and 3 in 21%. No dose relationship between SF-SRS dose and PNS injury was detected.

CONCLUSIONS

Single-fraction SRS to the spine can result in PNS injury with major implications for function and quality of life.