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Ronny Kalash, Scott M. Glaser, John C. Flickinger, Steven Burton, Dwight E. Heron, Peter C. Gerszten, Johnathan A. Engh, Nduka M. Amankulor and John A. Vargo

OBJECTIVE

Akin to the nonoperative management of benign intracranial tumors, stereotactic body radiation therapy (SBRT) has emerged as a nonoperative treatment option for noninfiltrative primary spine tumors such as meningioma and schwannoma. The majority of initial series used higher doses of 16–24 Gy in 1–3 fractions. The authors hypothesized that lower doses (such as 12–13 Gy in 1 fraction) might provide an efficacy similar to that found with the dose de-escalation commonly used for intracranial radiosurgery to treat acoustic neuroma or meningioma and with a lower risk of toxicity.

METHODS

The authors identified 38 patients in a prospectively maintained institutional radiosurgery database who were treated with definitive SBRT for a total of 47 benign primary spine tumors between 2004 and 2016. SBRT consisted of 9–21 Gy in 1–3 fractions using the CyberKnife (n = 11 [23%]), Synergy S (n = 21 [45%]), or TrueBeam (n = 15 [32%]) radiosurgery platform. For a comparison of SBRT doses, patients were dichotomized into 1 of 2 groups (low-dose or high-dose SBRT) using a cutoff biologically effective dose (BED10Gy) of 30 Gy. Tumor control was calculated from the date of SBRT to the last follow-up using Kaplan-Meier survival analysis, with comparisons between groups completed using a log-rank method. To account for potential indication bias, a propensity score analysis was completed based on the conditional probabilities of SBRT dose selection. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4.0 with a focus on grade 3+ toxicity and the incidence of pain flare.

RESULTS

For the 38 patients, the most common histological findings were meningioma (15 patients), schwannoma (13 patients), and hemangioblastoma (7 patients). The median age at SBRT was 58 years (range 25–91 years). The 47 treated lesions were located in the cervical (n = 18), thoracic (n = 19), or lumbosacral (n = 10) spine. Five (11%) lesions were lost to follow-up after SBRT. The median follow-up duration for the remaining 42 lesions was 54 months (range 1.2–133 months). Six (16%) patients (with a total of 8 lesions) experienced pain flare after SBRT; no significant predictor of pain flare was identified. No grade 3+ acute- or late-onset complication was noted. The 5-year local control rate was 76% (95% CI 61%–91%). No significant difference in local control according to dose, fractionation, previous radiation, surgery, tumor histology, age, treatment platform, planning target volume, or spine level treated was found. The 5-year local control rates for low- and high-dose treatments were 73% (95% CI 53%–93%) and 83% (95% CI 61%–100%) (p = 0.52). In propensity score–adjusted multivariable analysis, no difference in local control was identified (HR 0.30, 95% CI 0.02–5.40; p = 0.41).

CONCLUSIONS

Long-term follow-up of patients treated with SBRT for benign spinal lesions revealed no significant difference between low-dose (BED10Gy ≤ 30) and high-dose SBRT in local control, pain-flare rate, or long-term toxicity.

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Nitin Agarwal, Prateek Agarwal, Ashley Querry, Anna Mazurkiewicz, Zachary J. Tempel, Robert M. Friedlander, Peter C. Gerszten, D. Kojo Hamilton, David O. Okonkwo and Adam S. Kanter

OBJECTIVE

Previous studies have demonstrated the efficacy of infection prevention protocols in reducing infection rates. This study investigated the effects of the development and implementation of an infection prevention protocol that was augmented by increased physician awareness of spinal fusion surgical site infection (SSI) rates and resultant cost savings.

METHODS

A cohort clinical investigation over a 10-year period was performed at a single tertiary spine care academic institution. Preoperative infection control measures (chlorohexidine gluconate bathing, Staphylococcus aureus nasal screening and decolonization) followed by postoperative infection control measures (surgical dressing care) were implemented. After the implementation of these infection control measures, an awareness intervention was instituted in which all attending and resident neurosurgeons were informed of their individual, independently adjudicated spinal fusion surgery infection rates and rankings among their peers. During the course of these interventions, the overall infection rate was tracked as well as the rates for those neurosurgeons who complied with the preoperative and postoperative infection control measures (protocol group) and those who did not (control group).

RESULTS

With the implementation of postoperative surgical dressing infection control measures and physician awareness, the postoperative spine surgery infection rate decreased by 45% from 3.8% to 2.1% (risk ratio 0.55; 95% CI 0.32–0.93; p = 0.03) for those in the protocol cohort, resulting in an estimated annual cost savings of $291,000. This reduction in infection rate was not observed for neurosurgeons in the control group, although the overall infection rate among all neurosurgeons decreased by 54% from 3.3% to 1.5% (risk ratio 0.46; 95% CI 0.28–0.73; p = 0.0013).

CONCLUSIONS

A novel paradigm for spine surgery infection control combined with physician awareness methods resulted in significantly decreased SSI rates and an associated cost reduction. Thus, information sharing and physician engagement as a supplement to formal infection control measures result in improvements in surgical outcomes and costs.

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Kristin J. Redmond, Simon S. Lo, Scott G. Soltys, Yoshiya Yamada, Igor J. Barani, Paul D. Brown, Eric L. Chang, Peter C. Gerszten, Samuel T. Chao, Robert J. Amdur, Antonio A. F. De Salles, Matthias Guckenberger, Bin S. Teh, Jason Sheehan, Charles R. Kersh, Michael G. Fehlings, Moon-Jun Sohn, Ung-Kyu Chang, Samuel Ryu, Iris C. Gibbs and Arjun Sahgal

OBJECTIVE

Although postoperative stereotactic body radiation therapy (SBRT) for spinal metastases is increasingly performed, few guidelines exist for this application. The purpose of this study is to develop consensus guidelines to promote safe and effective treatment for patients with spinal metastases.

METHODS

Fifteen radiation oncologists and 5 neurosurgeons, representing 19 centers in 4 countries and having a collective experience of more than 1300 postoperative spine SBRT cases, completed a 19-question survey about postoperative spine SBRT practice. Responses were defined as follows: 1) consensus: selected by ≥ 75% of respondents; 2) predominant: selected by 50% of respondents or more; and 3) controversial: no single response selected by a majority of respondents.

RESULTS

Consensus treatment indications included: radioresistant primary, 1–2 levels of adjacent disease, and previous radiation therapy. Contraindications included: involvement of more than 3 contiguous vertebral bodies, ASIA Grade A status (complete spinal cord injury without preservation of motor or sensory function), and postoperative Bilsky Grade 3 residual (cord compression without any CSF around the cord). For treatment planning, co-registration of the preoperative MRI and postoperative T1-weighted MRI (with or without gadolinium) and delineation of the cord on the T2-weighted MRI (and/or CT myelogram in cases of significant hardware artifact) were predominant. Consensus GTV (gross tumor volume) was the postoperative residual tumor based on MRI. Predominant CTV (clinical tumor volume) practice was to include the postoperative bed defined as the entire extent of preoperative tumor, the relevant anatomical compartment and any residual disease. Consensus was achieved with respect to not including the surgical hardware and incision in the CTV. PTV (planning tumor volume) expansion was controversial, ranging from 0 to 2 mm. The spinal cord avoidance structure was predominantly the true cord. Circumferential treatment of the epidural space and margin for paraspinal extension was controversial. Prescription doses and spinal cord tolerances based on clinical scenario, neurological compromise, and prior overlapping treatments were controversial, but reasonable ranges are presented. Fifty percent of those surveyed practiced an integrated boost to areas of residual tumor and density override for hardware within the beam path. Acceptable PTV coverage was controversial, but consensus was achieved with respect to compromising coverage to meet cord constraint and fractionation to improve coverage while meeting cord constraint.

CONCLUSIONS

The consensus by spinal radiosurgery experts suggests that postoperative SBRT is indicated for radioresistant primary lesions, disease confined to 1–2 vertebral levels, and/or prior overlapping radiotherapy. The GTV is the postoperative residual tumor, and the CTV is the postoperative bed defined as the entire extent of preoperative tumor and anatomical compartment plus residual disease. Hardware and scar do not need to be included in CTV. While predominant agreement was reached about treatment planning and definition of organs at risk, future investigation will be critical in better understanding areas of controversy, including whether circumferential treatment of the epidural space is necessary, management of paraspinal extension, and the optimal dose fractionation schedules.

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Jesse D. Lawrence, Andrew M. Frederickson, Yue-Fang Chang, Patricia M. Weiss, Peter C. Gerszten and Raymond F. Sekula Jr.

OBJECTIVE

Hemifacial spasm (HFS) is a movement disorder characterized by involuntary spasms of the facial muscles, and it can negatively impact quality of life (QOL). This retrospective study and systematic review with meta-analysis was conducted to investigate the QOL in patients with HFS following intervention with microvascular decompression (MVD) and botulinum toxin (BT).

METHODS

In the retrospective analysis, a QOL questionnaire was administered to all patients undergoing MVD performed by a single surgeon. The QOL questionnaire included unique questions developed based on the authors' experience with HFS patients in addition to the health-related QOL HFS-8 questionnaire. The authors also report on a systematic review of the English literature providing outcomes and complications in patients with HFS undergoing treatment with either MVD or BT.

RESULTS

Regarding the retrospective analysis, 242 of 331 patients completed the questionnaire. The mean score of the 10 QOL questions improved from 22.78 (SD 9.83) to 2.17 (SD 5.75) following MVD (p < 0.001). There was significant improvement across all subscales of the questionnaire between pre- and postoperative responses (p < 0.001). Regarding the systematic review, it is reported that approximately 90% of patients undergoing MVD for HFS experience a complete recovery from symptoms, whereas the mean peak improvement of symptoms following treatment with BT is 77%. Furthermore, patients undergoing MVD reported a greater improvement in the mean supplemental index of QOL as compared with patients receiving BT therapy.

CONCLUSIONS

Microvascular decompression offers a significant improvement in QOL in well-selected patients suffering from HFS, and may offer an increased benefit for QOL over BT injections.

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Mark H. Bilsky, Steven D. Chang, Peter C. Gerszten and Steven Kalkanis

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Andrés Monserrate, Benjamin Zussman, Alp Ozpinar, Ajay Niranjan, John C. Flickinger and Peter C. Gerszten

OBJECTIVE

Cone-beam CT (CBCT) image guidance technology has been widely adopted for spine radiosurgery delivery. There is relatively little experience with spine radiosurgery for intradural tumors using CBCT image guidance. This study prospectively evaluated a series of intradural spine tumors treated with radiosurgery. Patient setup accuracy for spine radiosurgery delivery using CBCT image guidance for intradural spine tumors was determined.

METHODS

Eighty-two patients with intradural tumors were treated and prospectively evaluated. The positioning deviations of the spine radiosurgery treatments in patients were recorded. Radiosurgery was delivered using a linear accelerator with a beam modulator and CBCT image guidance combined with a robotic couch that allows positioning correction in 3 translational and 3 rotational directions. To measure patient movement, 3 quality assurance CBCTs were performed and recorded in 30 patients: before, halfway, and after the radiosurgery treatment. The positioning data and fused images of planning CT and CBCT from the treatments were analyzed to determine intrafraction patient movements. From each of 3 CBCTs, 3 translational and 3 rotational coordinates were obtained.

RESULTS

The radiosurgery procedure was successfully completed for all patients. Lesion locations included cervical (22), thoracic (17), lumbar (38), and sacral (5). Tumor histologies included schwannoma (27), neurofibromas (18), meningioma (16), hemangioblastoma (8), and ependymoma (5). The mean prescription dose was 17 Gy (range 12–27 Gy) delivered in 1–3 fractions. At the halfway point of the radiation, the translational variations and standard deviations were 0.4 ± 0.5, 0.5 ± 0.8, and 0.4 ± 0.5 mm in the lateral (x), longitudinal (y), and anteroposterior (z) directions, respectively. Similarly, the variations immediately after treatment were 0.5 ± 0.4, 0.5 ± 0.6, and 0.6 ± 0.5 mm along x, y, and z directions, respectively. The mean rotational angles were 0.3° ± 0.4°, 0.3° ± 0.4°, and 0.3° ± 0.4° along yaw, roll, and pitch, respectively, at the halfway point and 0.5° ± 0.5°, 0.4° ± 0.5°, and 0.2° ± 0.3° immediately after treatment.

CONCLUSIONS

Radiosurgery offers an alternative treatment option for intradural spine tumors in patients who may not be optimal candidates for open surgery. CBCT image guidance for patient setup for spine radiosurgery is accurate and successful in patients with intradural tumors.

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The effect of vancomycin powder on human dural fibroblast culture and its implications for dural repair during spine surgery

Presented at the 2016 AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves

Ezequiel Goldschmidt, Jorge Rasmussen, Joseph D. Chabot, Gurpreet Gandhoke, Emilia Luzzi, Lina Merlotti, Romina Proni, Mónica Loresi, D. Kojo Hamilton, David O. Okonkwo, Adam S. Kanter and Peter C. Gerszten

OBJECTIVE

Surgical site infections (SSIs) are a major source of morbidity after spinal surgery. Several recent studies have described the finding that applying vancomycin powder to the surgical bed may reduce the incidence of SSI. However, applying vancomycin in high concentrations has been shown in vitro to inhibit osteoblast proliferation and to induce cell death. Vancomycin may have a deleterious effect on dural healing after repair of an intentional or unintentional durotomy. This study was therefore undertaken to assess the effect of different concentrations of vancomycin on a human dura mater cell culture.

METHODS

Human dura intended for disposal after decompressive craniectomy was harvested. Explant primary cultures and subcultures were subsequently performed. Cells were characterized through common staining and immunohistochemistry. A growth curve was performed to assess the effect of different concentrations of vancomycin (40, 400, and 4000 μg/ml) on cell count. The effect of vancomycin on cellular shape, intercellular arrangement, and viability was also evaluated.

RESULTS

All dural tissue samples successfully developed into fusiform cells, demonstrating pseudopod projections and spindle formation. The cells demonstrated vimentin positivity and also had typical features of fibroblasts. When applied to the cultures, the highest dose of vancomycin induced generalized cell death within 24 hours. The mean (± SD) cell counts for control, 40, 400, and 4000 μg/ml were 38.72 ± 15.93, 36.28 ± 22.87, 19.48 ± 6.53, and 4.07 ± 9.66, respectively (p < 0.0001, ANOVA). Compared with controls, vancomycin-exposed cells histologically demonstrated a smaller cytoplasm and decreased pseudopodia formation resulting in the inhibition of normal spindle intercellular arrangement.

CONCLUSIONS

When vancomycin powder is applied locally, dural cells are exposed to a concentration several times greater than when delivered systemically. In this in vitro model, vancomycin induced dural cell death, inhibited growth, and altered cellular morphology in a concentration-dependent fashion. Defining a safe vancomycin concentration that is both bactericidal and also does not inhibit normal dural healing is necessary.

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Ahmed Hashmi, Matthias Guckenberger, Ron Kersh, Peter C. Gerszten, Frederick Mantel, Inga S. Grills, John C. Flickinger, John H. Shin, Daniel K. Fahim, Brian Winey, Kevin Oh, B. C. John Cho, Daniel Létourneau, Jason Sheehan and Arjun Sahgal

OBJECTIVE

This study is a multi-institutional pooled analysis specific to imaging-based local control of spinal metastases in patients previously treated with conventional external beam radiation therapy (cEBRT) and then treated with re-irradiation stereotactic body radiotherapy (SBRT) to the spine as salvage therapy, the largest such study to date.

METHODS

The authors reviewed cases involving 215 patients with 247 spinal target volumes treated at 7 institutions. Overall survival was calculated on a patient basis, while local control was calculated based on the spinal target volume treated, both using the Kaplan-Meier method. Local control was defined as imaging-based progression within the SBRT target volume. Equivalent dose in 2-Gy fractions (EQD2) was calculated for the cEBRT and SBRT course using an α/β of 10 for tumor and 2 for both spinal cord and cauda equina.

RESULTS

The median total dose/number of fractions of the initial cEBRT was 30 Gy/10. The median SBRT total dose and number of fractions were 18 Gy and 1, respectively. Sixty percent of spinal target volumes were treated with single-fraction SBRT (median, 16.6 Gy and EQD2/10 = 36.8 Gy), and 40% with multiple-fraction SBRT (median 24 Gy in 3 fractions, EQD2/10 = 36 Gy). The median time interval from cEBRT to re-irradiation SBRT was 13.5 months, and the median duration of patient follow-up was 8.1 months. Kaplan-Meier estimates of 6- and 12-month overall survival rates were 64% and 48%, respectively; 13% of patients suffered a local failure, and the 6- and 12-month local control rates were 93% and 83%, respectively. Multivariate analysis identified Karnofsky Performance Status (KPS) < 70 as a significant prognostic factor for worse overall survival, and single-fraction SBRT as a significant predictive factor for better local control. There were no cases of radiation myelopathy, and the vertebral compression fracture rate was 4.5%.

CONCLUSIONS

Re-irradiation spine SBRT is effective in yielding imaging-based local control with a clinically acceptable safety profile. A randomized trial would be required to determine the optimal fractionation.

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Nathan T. Zwagerman, Michael M. McDowell, Ronald L. Hamilton, Edward A. Monaco III, John C. Flickinger and Peter C. Gerszten

OBJECTIVE

Increased survival time after diagnosis of neoplastic disease has resulted in a gradual increase in spine tumor incidence. Radiosurgery is frequently a viable alternative to operative management in a population with severe medical comorbidities. The authors sought to assess the histopathological consequences of radiosurgery in the subset of patients progressing to operative intervention.

METHODS

Eighteen patients who underwent radiosurgery for spine tumors between 2008 and 2014 subsequently progressed to surgical treatment. A histopathological examination of these cases was performed. Indications for surgery included symptomatic compression fractures, radiographic instability, and symptoms of cord or cauda equina compression. Biopsy samples were obtained from the tumor within the radiosurgical zone in all cases and were permanently fixated. Viable tumor samples were stained for Ki 67.

RESULTS

Fifteen patients had metastatic lesions and 3 patients had neurofibromas. The mean patient age was 57 years. The operative indication was symptomatic compression in 10 cases (67%). The most frequent metastatic lesions were breast cancer (4 cases), renal cell carcinoma (3), prostate cancer (2), and endometrial cancer (2). In 9 (60%) of the 15 metastatic cases, histological examination of the lesions showed minimal evidence of inflammation. Viable tumor at the margins of the radiosurgery was seen in 9 (60%) of the metastatic cases. Necrosis in the tumor bed was frequent, as was fibrotic bone marrow. Vascular ectasia was seen in 2 of 15 metastatic cases, but sclerosis with ectasia was frequent. No evidence of malignant conversion was seen in the periphery of the lesions in the 3 neurofibroma cases. In 1 case of neurofibroma, the lesion demonstrated some small areas of remnant tumor in the radiosurgical target zone.

CONCLUSIONS

This case series demonstrates important histopathological characteristics of spinal lesions treated by SRS. Regions with the highest exposure to radiation appear to be densely necrotic and show little evidence of tumor growth, whereas peripheral regions distant from the radiation dosage are more likely to demonstrate viable tumor in malignant and benign neoplasms. Physiological tissue appears to be similarly affected. With additional investigation, a more homogenized field of hypofractionated radiation exposure may allow for tumor obliteration with relative preservation of critical anatomical structures.