Mark H. Bilsky and Yoshiya Yamada
Ori Barzilai, Lily McLaughlin, Eric Lis, Yoshiya Yamada, Mark H. Bilsky, and Ilya Laufer
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.
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.
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.
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.
Evangelia Katsoulakis, Ilya Laufer, Mark Bilsky, Narasimhan P. Agaram, Michael Lovelock, and Yoshiya Yamada
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.
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.
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).
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.
Presented at the 2009 Joint Spine Section Meeting
Ilya Laufer, Andrew Hanover, Eric Lis, Yoshiya Yamada, and Mark Bilsky
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.
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.
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.
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.
Evangelia Katsoulakis, Nadeem Riaz, Brett Cox, James Mechalakos, Joan Zatcky, Mark Bilsky, and Yoshiya Yamada
The objective of this study was to investigate the feasibility and safety of delivering a third course of radiation to patients with multiply recurrent metastatic disease to the spine.
Between 2009 and 2011, 10 patients received a third course of radiation to spinal metastases at Memorial Sloan–Kettering Cancer Center using image-guided intensity-modulated radiation therapy (IMRT). Patient and tumor characteristics, dosimetry details, and outcomes were obtained using retrospective chart review. Spinal imaging was performed prior to treatment and at regular follow-up intervals. The cumulative biologically effective dose (BED) to the spinal cord and cauda equina was calculated and was normalized to 2 Gy equivalents (Gy2/2). Toxicity and local control were assessed.
The median time between the first and second courses of radiation was 18.5 months and the median time between the second and third courses was 11.5 months. The median follow-up from the third course of radiation was 12 months and the median overall survival was 13 months. Pain or neurological symptoms were improved in 80% of patients. The median spinal cord maximum dose normalized BED (nBED) for the whole cohort was 70.73 Gy2/2 (range 51.9–101.7 Gy2/2). The median dose to 5% of the spinal cord D05 nBED for the entire cohort was 59.4 Gy2/2. Acute toxicity was most commonly fatigue and dermatitis, with 1 patient experiencing Grade 3 fatigue and 1 patient Grade 3 dermatitis. Late toxicity was limited to 2 cases of Grade 1 dysphagia. There was 1 case of Grade 1 neuropathy and 1 case of Grade 2 neuropathy. The crude rate of local control was 80% with 1 in-field failure and 1 marginal failure.
In this cohort of patients, a third course of IMRT to the spine was well tolerated with no significant late toxicities. Used as salvage therapy for select patients, a third course of radiation is a safe and effective treatment strategy.
Athos Patsalides, Yoshiya Yamada, Mark Bilsky, Eric Lis, Ilya Laufer, and Yves Pierre Gobin
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.
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.
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.
These preliminary results support the hypothesis that SIAC is feasible and safe.
Ilya Laufer, J. Bryan Iorgulescu, Talia Chapman, Eric Lis, Weiji Shi, Zhigang Zhang, Brett W. Cox, Yoshiya Yamada, and Mark H. Bilsky
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.
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.
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.
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%).
Ori Barzilai, Natalie DiStefano, Eric Lis, Yoshiya Yamada, D. Michael Lovelock, Andrew N. Fontanella, Mark H. Bilsky, and Ilya Laufer
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.
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.
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.
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.
William Y. Tong, Michael R. Folkert, Jeffrey P. Greenfield, Yoshiya Yamada, and Suzanne L. Wolden
Achieving local control is a crucial component in the management of neuroblastoma, but this may be complicated in the setting of prior radiation treatment, especially when the therapeutic target is in proximity to critical structures such as the spinal cord. The authors describe a pediatric patient with multiply recurrent neuroblastoma and prior high-dose radiation therapy to the spine who presented with progressive epidural disease. The patient was managed with resection and intraoperative high-dose-rate brachytherapy using a phosphorus-32 (32P) plaque previously developed for the treatment of brain and spine lesions.
Michael D. Stubblefield, Katarzyna Ibanez, Elyn R. Riedel, Ori Barzilai, Ilya Laufer, Eric Lis, Yoshiya Yamada, and Mark H. Bilsky
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.
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.
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.
Single-fraction SRS to the spine can result in PNS injury with major implications for function and quality of life.