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Ilya Laufer and Mark H. Bilsky

An improved understanding of tumor biology, the ability to target tumor drivers, and the ability to harness the immune system have dramatically improved the expected survival of patients diagnosed with cancer. However, many patients continue to develop spine metastases that require local treatment with radiotherapy and surgery. Fortunately, the evolution of radiation delivery and operative techniques permits durable tumor control with a decreased risk of treatment-related toxicity and a greater emphasis on restoration of quality of life and daily function. Stereotactic body radiotherapy allows delivery of ablative radiation doses to the majority of spine tumors, reducing the need for surgery. Among patients who still require surgery for decompression of the spinal cord or spinal column stabilization, minimal access approaches and targeted tumor excision and ablation techniques minimize the surgical risk and facilitate postoperative recovery. Growing interdisciplinary collaboration among scientists and clinicians will further elucidate the synergistic possibilities among systemic, radiation, and surgical interventions for patients with spinal tumors and will bring many closer to curative therapies.

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Theresa Kraetzig, Lily McLaughlin, Mark H. Bilsky and Ilya Laufer

OBJECTIVE

Myxopapillary ependymoma is a benign WHO Grade I tumor most commonly located in the conus–cauda equina region of the spine. Although this tumor is defined by an overall excellent survival, dissemination throughout the whole neuraxis occurs frequently. The current study evaluated the clinical characteristics and significance of myxopapillary ependymoma metastases.

METHODS

Patients who underwent surgery from 2005 to 2015 for treatment of spinal myxopapillary ependymoma were included in the study. Charts were reviewed for primary tumor symptoms and initial treatment, local recurrence, response to salvage therapy, and presence and behavior of distant metastases.

RESULTS

Nineteen patients with spinal myxopapillary ependymoma were included in the study (52.6% female). The median age at first diagnosis was 32 years old (range 9–58 years old), and 26.3% were ≤ 18 years old. The median follow-up of all included patients was 48 months (range 6–456 months). Of the primary tumors, 84.2% were located in the lower thoracic or upper lumbar spine, spanning 1–3 levels in 94.7%. All patients underwent surgery for initial treatment: in 78.9% a gross-total resection (GTR) was achieved, with adjuvant radiation therapy (RT) in 20%. Of the 21.2% who underwent a subtotal resection (STR), 75% underwent postoperative RT. Tumor progression was noted in 26.3% of patients after a median 36-month follow-up (range 12–240 months). In 57.9% of patients, distant metastases were found, of which 36.4% were present at initial diagnosis. Further metastases occurred within a median of 20 months (range 2–360 months). Following a diagnosis of metastatic tumor, 72.7% did not show progression and no symptoms were observed during a median follow-up of 36 months (range 6–216 months). Metastases occurred in all parts of the neuroaxis, but were principally localized in the thoracic and sacral spine in 38.9% and 33.3%, respectively; the brain was involved in 11.1%. In 54.5%, more than 1 level was affected. Overall survival was 100% with an excellent clinical and neurological outcome in 78.9% of cases.

CONCLUSIONS

Metastatic dissemination within the CNS can be observed in many patients with myxopapillary ependymoma. GTR of the primary tumor should be the primary treatment goal, and additional RT is recommended after STR. For distant metastases of myxopapillary ependymoma without clinical manifestation, close clinical and MRI follow-up represents a sufficient strategy because most of the metastases remain asymptomatic and do not show progression over time. Additional resection or irradiation as salvage therapy would be recommended if metastases become symptomatic.

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Ilya Laufer, Vijay K. Anand and Theodore H. Schwartz

Object

The extended transsphenoidal approach is a less invasive method for removing purely suprasellar lesions compared with traditional transcranial approaches. Most advocates have used a sublabial incision and a microscope and have reported a significant risk of cerebrospinal fluid (CSF) leakage. The authors report on a series of purely endoscopic endonasal surgeries for resection of suprasellar supradiaphragmatic lesions above a normal-sized sella turcica with a low risk of CSF leakage.

Methods

A purely endoscopic endonasal approach was used to remove suprasellar lesions in a series of 10 patients. Five lesions were prechiasmal (three tuberculum sellae and two planum sphenoidale meningiomas) and five were post-chiasmal (four craniopharyngiomas and one Rathke cleft cyst). The floor of the planum sphenoidale and the sella turcica was reconstructed using a multilayer closure with autologous and synthetic materials. Spinal drainage was performed in only five cases. Complete resection of the lesions was achieved in all but one patient. The pituitary stalk was preserved in all but one patient, whose stalk was invaded by a craniopharyngioma and who had preoperative diabetes insipidus (DI). Vision improved postoperatively in all patients with preoperative impairment. Six patients had temporary DI; in five, the DI became permanent. Four patients with craniopharyngiomas required cortisone and thyroid replacement. After a mean follow up of 10 months, there was only one transient CSF leak when a lumbar drain was clamped prematurely on postoperative Day 5.

Conclusions

A purely endoscopic endonasal approach to suprasellar supradiaphragmatic lesions is a feasible minimally invasive alternative to craniotomy. With a multilayer closure, the risk of CSF leakage is low and lumbar drainage can be avoided. A larger series will be required to validate this approach.

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Ilya Laufer, Murray Engel, Neil Feldstein and Mark M. Souweidane

✓Chiari malformations may present with a wide range of symptoms and signs. Nevertheless, focal foot weakness as a presentation of a Chiari malformation has not been described in the pediatric neurosurgical literature. Two children with Chiari malformations and holocord syringomyelia presented with manifestations of a supposed isolated lumbar radiculopathy. Neurological deficits completely resolved after decompressive suboccipital craniectomy and cervical laminectomy. These cases emphasize the importance of imaging the entire craniospinal axis and avoidance of therapeutic intervention specifically aimed at a radiculopathic process when initial imaging fails to show a structural abnormality at the spinal level of deficit. The possible pathophysiological origins for this unusual presentation are discussed. Based on the experience gained with these patients, recommendations are made regarding the diagnostic workup and management of this entity in children presenting with focal deficits that are not supported by imaging of the affected root levels. Chiari malformations may rarely masquerade as lower motor and sensory deficits, and appropriate treatment may result in excellent recovery of function.

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Repeat decompression surgery for recurrent spinal metastases

Presented at the 2009 Joint Spine Section Meeting

Ilya Laufer, Andrew Hanover, Eric Lis, Yoshiya Yamada and Mark Bilsky

Object

In this paper, the authors' goal was to determine the outcome of reoperation for recurrent epidural spinal cord compression in patients with metastatic spine disease.

Methods

A retrospective chart review was conducted of all patients who underwent spine surgery at the Memorial Sloan-Kettering Cancer Center between 1996 and 2007. Thirty-nine patients who underwent reoperation of the spine at the level previously treated with surgery were identified. Only patients whose reoperation was performed because of tumor recurrence leading to high-grade epidural spinal cord compression or recurrence with no further radiation options were included in the study. Patients who underwent reoperations exclusively for instrumentation failure were excluded. All patients underwent additional decompression via a posterolateral approach without removal of the spinal instrumentation.

Results

Patients underwent 1–4 reoperations at the same level. A median survival time of 12.4 months was noted after the first reoperation, and a median survival time of 9.1 months was noted after the last reoperation. At last follow-up 22 (65%) of 34 patients were ambulatory at the time of last follow-up or death, and the median time between loss-of-ambulation and death was 1 month. Functional status was maintained or improved by one Eastern Cooperative Oncology Group grade in 97% of patients. A major surgical complication rate of 5% was noted.

Conclusions

Reoperation represents a viable option in patients with high-grade epidural spinal cord compression who have recurrent metastatic tumors at previously operated spinal levels. In carefully selected patients, reoperation can prolong ambulation and result in good functional and neurological outcomes.

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Athos Patsalides, Yoshiya Yamada, Mark Bilsky, Eric Lis, Ilya Laufer and Yves Pierre Gobin

OBJECT

Despite advances in therapies using radiation oncology and spinal oncological surgery, there is a subgroup of patients with spinal metastases who suffer from progressive or recurrent epidural disease and remain at risk for neurological compromise. In this paper the authors describe their initial experience with a novel therapeutic approach that consists of intraarterial (IA) infusion of chemotherapy to treat progressive spinal metastatic disease.

METHODS

The main inclusion criterion was the presence of progressive, metastatic epidural disease to the spine causing spinal canal compromise in patients who were not candidates for the standard treatments of radiation therapy and/or surgery. All tumor histological types were eligible for this trial. Using the transfemoral arterial approach and standard neurointerventional techniques, all patients were treated with IA infusion of melphalan in the arteries supplying the epidural tumor. The protocol allowed for up to 3 procedures repeated at 3- to 6-week intervals. Outcome measures included physiological measures: 1) periprocedural complications according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events; and 2) MRI to assess for tumor response.

RESULTS

Nine patients with progressive spinal metastatic disease and cord compression were enrolled in a Phase I clinical trial of selective IA chemotherapy. All patients had metastatic disease from solid organs and were not candidates for further radiation therapy or surgery. A total of 19 spinal intraarterial chemotherapy (SIAC) procedures were performed, and the follow-up period ranged from 1 to 7 months (median 3 months). There was 1 serious adverse event (febrile neutropenia). Local tumor control was seen in 8 of 9 patients, whereas tumor progression at the treated level was seen in 1 patient.

CONCLUSIONS

These preliminary results support the hypothesis that SIAC is feasible and safe.

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Evangelia Katsoulakis, Ilya Laufer, Mark Bilsky, Narasimhan P. Agaram, Michael Lovelock and Yoshiya Yamada

OBJECTIVE

Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may makeit difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery.

METHODS

Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator–based single-fraction (18–24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method.

RESULTS

The mean age at the time of radiosurgery was 59 years (range 36–80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant tumor types, including renal cell carcinoma in 7 (22%), melanoma in 6 (19%), lung carcinoma in 4 (12%), and sarcoma in 3 (9%). The median time to surgical intervention was 24.7 months (range 1.6–50.8 months). The median follow-up and overall survival for all patients were 42.5 months and 41 months (overall survival range 7–86 months), respectively. The majority of assessed lesions showed no evidence of tumor on pathological review (25 of 32, 78%), while a minority of lesions revealed residual tumor (7 of 32, 22%). The median survival for patients after tumor recurrence was 5 months (range 2–70 months).

CONCLUSIONS

High-dose single-fraction radiosurgery is tumor ablative in the majority of instances. In a minority of cases, tumor persists and salvage treatments should be considered.

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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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Ilya Laufer, J. Bryan Iorgulescu, Talia Chapman, Eric Lis, Weiji Shi, Zhigang Zhang, Brett W. Cox, Yoshiya Yamada and Mark H. Bilsky

Object

Decompression surgery followed by adjuvant radiotherapy is an effective therapy for preservation or recovery of neurological function and achieving durable local disease control in patients suffering from metastatic epidural spinal cord compression (ESCC). The authors examine the outcomes of postoperative image-guided intensity-modulated radiation therapy delivered as single-fraction or hypofractionated stereotactic radiosurgery (SRS) for achieving long-term local tumor control.

Methods

A retrospective chart review identified 186 patients with ESCC from spinal metastases who were treated with surgical decompression, instrumentation, and postoperative radiation delivered as either single-fraction SRS (24 Gy) in 40 patients (21.5%), high-dose hypofractionated SRS (24–30 Gy in 3 fractions) in 37 patients (19.9%), or low-dose hypofractionated SRS (18–36 Gy in 5 or 6 fractions) in 109 patients (58.6%). The relationships between postoperative adjuvant SRS dosing and fractionation, patient characteristics, tumor histology–specific radiosensitivity, grade of ESCC, extent of surgical decompression, response to preoperative radiotherapy, and local tumor control were evaluated by competing risks analysis.

Results

The total cumulative incidence of local progression was 16.4% 1 year after SRS. Multivariate Gray competing risks analysis revealed a significant improvement in local control with high-dose hypofractionated SRS (4.1% cumulative incidence of local progression at 1 year, HR 0.12, p = 0.04) as compared with low-dose hypofractionated SRS (22.6% local progression at 1 year, HR 1). Although univariate analysis demonstrated a trend toward greater risk of local progression for patients in whom preoperative conventional external beam radiation therapy failed (22.2% local progression at 1 year, HR 1.96, p = 0.07) compared with patients who did not receive any preoperative radiotherapy (11.2% local progression at 1 year, HR 1), this association was not confirmed with multivariate analysis. No other variable significantly correlated with progression-free survival, including radiation sensitivity of tumor histology, grade of ESCC, extent of surgical decompression, or patient sex.

Conclusions

Postoperative adjuvant SRS following epidural spinal cord decompression and instrumentation is a safe and effective strategy for establishing durable local tumor control regardless of tumor histology–specific radiosensitivity. Patients who received high-dose hypofractionated SRS demonstrated 1-year local progression rates of less than 5% (95% CI 0%–12.2%), which were superior to the results of low-dose hypofractionated SRS. The local progression rate after single-fraction SRS was less than 10% (95% CI 0%–19.0%).