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Jonathan N. Sellin, William Reichardt, Andrew J. Bishop, Dima Suki, Laurence D. Rhines, Stephen H. Settle, Paul D. Brown, Jing Li, Ganesh Rao, Eric L. Chang and Claudio E. Tatsui

OBJECT

Palliative resection of renal cell carcinoma (RCC) spinal metastasis is indicated in cases of neurological compromise or mechanical instability, whereas conventional external beam radiotherapy (EBRT) is commonly used for pain control. Recently, spinal stereotactic radiosurgery (SRS) has emerged as a safe alternative, delivering higher therapeutic doses of radiation to spinal metastases. To better understand factors affecting survival in patients undergoing spinal SRS for metastatic RCC, the authors performed a retrospective analysis of a consecutive series of cases at a tertiary cancer center.

METHODS

Patients harboring contiguous sites of vertebral body involvement from metastatic RCC who received upfront spinal SRS treatment at The University of Texas MD Anderson Cancer Center between 2005 and 2012 were identified. Demographic data, pain scores, radiographic data, overall survival, complications, status of systemic disease, neurological and functional status, and time between primary diagnosis and diagnosis of metastasis (systemic and spinal) were analyzed to determine their influence on survival.

RESULTS

Thirty-seven patients receiving treatment for 40 distinct, contiguous sites of disease were included. The median overall survival after spinal SRS was 16.3 months (range 7.4–25.3 months). Univariate analysis revealed several factors significantly associated with improved overall survival. Local progression after spinal SRS was associated with worse overall survival compared with sustained local control (HR 3.4, 95% CI 1.6–7.4, p = 0.002). Median survival in patients with a Karnofsky Performance Scale (KPS) score ≥ 70 was longer than in patients with a KPS score < 70 (HR 4.7, 95% CI 2.1–10.7, p < 0.001). Patients with neurological deficits at the time of spinal SRS had a shorter median survival than those without (HR 4.2, 95% CI 1.4–12.0, p = 0.008). Individuals with nonprogressive systemic disease at the time of spinal SRS had a longer median survival than those with systemic progression at the time of treatment (HR 8.3, 95% CI 3.3–20.7, p < 0.001). Median survival in patients experiencing any metastasis < 12 months after primary RCC diagnosis was shorter than in patients experiencing any metastasis > 12 months after primary diagnosis, a difference that approached but did not attain significance (HR 1.9, 95% CI 0.90–4.1, p = 0.09). On multivariate analysis, local progression of disease after spinal SRS, metastasis < 12 months after primary, KPS score ≤ 70, and progression of systemic disease at time of spinal SRS all remained significant factors influencing survival (respectively, HR 3.7, p = 0.002; HR 2.6, p = 0.026; HR 4.0, p = 0.002; and HR 13.2, p < 0.001).

CONCLUSIONS

We identified several factors associated with survival after spinal SRS for RCC metastases, including local progression, time between first metastasis and primary RCC diagnosis, KPS score, presence of neurological deficits, and progressive metastatic disease. These factors should be taken into consideration when considering a patient for spinal SRS for RCC metastases.

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Andrew J. Bishop, Randa Tao, B. Ashleigh Guadagnolo, Pamela K. Allen, Neal C. Rebueno, Xin A. Wang, Behrang Amini, Claudio E. Tatsui, Laurence D. Rhines, Jing Li, Eric L. Chang, Paul D. Brown and Amol J. Ghia

OBJECTIVE

Given the relatively lower radiosensitivity of sarcomas and the locally infiltrative patterns of spread, the authors sought to investigate spine stereotactic radiosurgery (SSRS) outcomes for metastatic sarcomas and to analyze patterns of failure.

METHODS

The records of 48 patients with 66 sarcoma spinal metastases consecutively treated with SSRS between 2002 and 2013 were reviewed. The Kaplan-Meier method was used to estimate rates of overall survival (OS) and local control (LC). Local recurrences were categorized as occurring infield (within the 95% isodose line [IDL]), marginally (between the 20% and 95% IDLs), or out of field.

RESULTS

Median follow-up time was 19 months (range 1–121 months), and median age was 53 years (range 17–85 years). The most commonly treated histology was leiomyosarcoma (42%). Approximately two-thirds of the patients were treated with definitive SSRS (44 [67%]) versus postoperatively (22 [33%]). The actuarial 1-year OS and LC rates were 67% and 81%, respectively. Eighteen patients had a local relapse, which was more significantly associated with postoperative SSRS (p = 0.04). On multivariate modeling, receipt of postoperative SSRS neared significance for poorer LC (p = 0.06, subhazard ratio [SHR] 2.33), while only 2 covariates emerged as significantly correlated with LC: 1) biological equivalent dose (BED) > 48 Gy (vs BED ≤ 48 Gy, p = 0.006, SHR 0.21) and 2) single vertebral body involvement (vs multiple bodies, p = 0.03, SHR 0.27). Of the 18 local recurrences, 14 (78%) occurred at the margin, and while the majority of these cases relapsed within the epidural space, 4 relapsed within the paraspinal soft tissue. In addition, 1 relapse occurred out of field. Finally, the most common acute toxicity was fatigue (15 cases), with few late toxicities (4 insufficiency fractures, 3 neuropathies).

CONCLUSIONS

For metastatic sarcomas, SSRS provides durable tumor control with minimal toxicity. High-dose single-fraction regimens offer optimal LC, and given the infiltrative nature of sarcomas, when paraspinal soft tissues are involved, larger treatment volumes may be warranted.

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Amol J. Ghia, Eric L. Chang, Andrew J. Bishop, Hubert Y. Pan, Nicholas S. Boehling, Behrang Amini, Pamela K. Allen, Jing Li, Laurence D. Rhines, Nizar M. Tannir, Claudio E. Tatsui, Paul D. Brown and James N. Yang

OBJECTIVE

The objective of this study was to compare fractionation schemes and outcomes of patients with renal cell carcinoma (RCC) treated in institutional prospective spinal stereotactic radiosurgery (SSRS) trials who did not previously undergo radiation treatment at the site of the SSRS.

METHODS

Patients enrolled in 2 separate institutional prospective protocols and treated with SSRS between 2002 and 2011 were included. A secondary analysis was performed on patients with previously nonirradiated RCC spinal metastases treated with either single-fraction (SF) or multifraction (MF) SSRS.

RESULTS

SSRS was performed in 47 spinal sites on 43 patients. The median age of the patients was 62 years (range 38–75 years). The most common histological subtype was clear cell (n = 30). Fifteen sites underwent surgery prior to the SSRS, with laminectomy the most common procedure performed (n = 10). All SF SSRS was delivered to a dose of 24 Gy (n = 21) while MF regiments were either 27 Gy in 3 fractions (n = 20) or 30 Gy in 5 fractions (n = 6). The median overall survival duration for the entire cohort was 22.8 months. The median local control (LC) for the entire cohort was 80.6 months with 1-year and 2-year actuarial LC rates of 82% and 68%, respectively. Single-fraction SSRS correlated with improved 1- and 2-year actuarial LC relative to MF SSRS (95% vs 71% and 86% vs 55%, respectively; p = 0.009). On competing risk analysis, SF SSRS showed superior LC to MF SSRS (subhazard ratio [SHR] 6.57, p = 0.014). On multivariate analysis for LC with tumor volume (p = 0.272), number of treated levels (p = 0.819), gross tumor volume (GTV) coverage (p = 0.225), and GTV minimum point dose (p = 0.97) as covariates, MF SSRS remained inferior to SF SSRS (SHR 5.26, p = 0.033)

CONCLUSIONS

SSRS offers durable LC for spinal metastases from RCC. Single-fraction SSRS is associated with improved LC over MF SSRS for previously nonirradiated RCC spinal metastases.

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Dhiego Chaves de Almeida Bastos, Richard George Everson, Bruno Fernandes de Oliveira Santos, Ahmed Habib, Rafael A. Vega, Marilou Oro, Ganesh Rao, Jing Li, Amol J. Ghia, Andrew J. Bishop, Debra Nana Yeboa, Behrang Amini, Laurence D. Rhines and Claudio Esteves Tatsui

OBJECTIVE

The proximity of the spinal cord to compressive metastatic lesions limits radiosurgical dosing. Open surgery is used to create safe margins around the spinal cord prior to spinal stereotactic radiosurgery (SSRS) but carries the risk of potential surgical morbidity and interruption of systemic oncological treatment. Spinal laser interstitial thermotherapy (SLITT) in conjunction with SSRS provides local control with less morbidity and a shorter interval to resume systemic treatment. The authors present a comparison between SLITT and open surgery in patients with metastatic thoracic epidural spinal cord compression to determine the advantages and disadvantages of each method.

METHODS

This is a matched-group design study comprising patients from a single institution with metastatic thoracic epidural spinal cord compression that was treated either with SLITT or open surgery. The two cohorts defined by the surgical treatment comprised patients with epidural spinal cord compression (ESCC) scores of 1c or higher and were deemed suitable for either treatment. Demographics, pre- and postoperative ESCC scores, histology, morbidity, hospital length of stay (LOS), complications, time to radiotherapy, time to resume systemic therapy, progression-free survival (PFS), and overall survival (OS) were compared between groups.

RESULTS

Eighty patients were included in this analysis, 40 in each group. Patients were treated between January 2010 and December 2016. There was no significant difference in demographics or clinical characteristics between the cohorts. The SLITT cohort had a smaller postoperative decrease in the extent of ESCC but a lower estimated blood loss (117 vs 1331 ml, p < 0.001), shorter LOS (3.4 vs 9 days, p < 0.001), lower overall complication rate (5% vs 35%, p = 0.003), fewer days until radiotherapy or SSRS (7.8 vs 35.9, p < 0.001), and systemic treatment (24.7 vs 59 days, p = 0.015). PFS and OS were similar between groups (p = 0.510 and p = 0.868, respectively).

CONCLUSIONS

The authors’ results have shown that SLITT plus XRT is not inferior to open decompression surgery plus XRT in regard to local control, with a lower rate of complications and faster resumption of oncological treatment. A prospective randomized controlled study is needed to compare SLITT with open decompressive surgery for ESCC.

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Kelsey L. Watson, Ghadah A. Al Sannaa, Christine M. Kivlin, Davis R. Ingram, Sharon M. Landers, Christina L. Roland, Janice N. Cormier, Kelly K. Hunt, Barry W. Feig, B. Ashleigh Guadagnolo, Andrew J. Bishop, Wei-Lien Wang, John M. Slopis, Ian E. McCutcheon, Alexandar J. Lazar and Keila E. Torres

OBJECTIVE

Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive group of soft tissue sarcomas that can arise sporadically, in the context of neurofibromatosis Type 1 (NF1) or at a site of prior irradiation. Large series profiling the features and outcomes of sporadic, NF1-associated, and radiation-associated MPNSTs are limited. The goal of this study was to elucidate differences between MPNST etiologies in a large single-institution retrospective study.

METHODS

Patients (n = 317) were identified through the tumor registry of The University of Texas MD Anderson Cancer Center. Clinicopathological features were retrospectively collected. Features were compared among MPNST subtypes for patients who had sufficient clinical history (n = 289), and clinicopathological features were used to identify adverse predictors of recurrence and survival outcomes.

RESULTS

Five-year local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and disease-specific survival (DSS) estimates were 56.6%, 49.6%, and 53.6%, respectively, for the high-grade MPNST cohort. Five-year DSS was lower in NF1-associated and radiation-associated MPNST than in sporadic MPNST (52%, 47%, and 67%, respectively, p = 0.140). Patients with radiation-associated MPNST had worse 5-year LRFS than those with the sporadic and NF1-associated subtypes (RT-associated vs sporadic, p = 0.010; RT-associated vs NF1-associated, p = 0.232). Truncally located tumors, positive surgical margins, local recurrence, and metastasis were predictors of adverse DSS in multivariate analysis.

CONCLUSIONS

Radiation-associated MPNSTs are associated with poorer local recurrence-free and disease-specific survival than sporadic and NF1-associated tumors. NF1-associated MPNSTs may have worse survival outcomes owing to large tumor size, compromising truncal location, and lower rate of negative resection margins compared with sporadic tumors.

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David Boyce-Fappiano, Olsi Gjyshi, Todd A. Pezzi, Pamela K. Allen, Moaaz Solimman, Nicolette Taku, Michael B. Bernstein, Maria E. Cabanillas, Behrang Amini, Claudio E. Tatsui, Laurence D. Rhines, Xin A. Wang, Tina M. Briere, Debra Nana Yeboa, Andrew J. Bishop, Jing Li and Amol J. Ghia

OBJECTIVE

Patients with metastatic thyroid cancer have prolonged survival compared to those with other primary tumors. The spine is the most common site of osseous involvement in cases of metastatic thyroid cancer. As a result, obtaining durable local control (LC) in the spine is crucial. This study aimed to evaluate the efficacy of spine stereotactic radiosurgery (SSRS) in patients with metastatic thyroid cancer.

METHODS

Information on patients with metastatic thyroid cancer treated with SSRS for spinal metastases was retrospectively evaluated. SSRS was delivered with a simultaneous integrated boost technique using single- or multiple-fraction treatments. LC, defined as stable or reduced disease volume, was evaluated by examining posttreatment MRI, CT, and PET studies.

RESULTS

A total of 133 lesions were treated in 67 patients. The median follow-up duration was 31 months. Dose regimens for SSRS included 18 Gy in 1 fraction, 27 Gy in 3 fractions, and 30 Gy in 5 fractions. The histology distribution was 36% follicular, 33% papillary, 15% medullary, 13% Hurthle cell, and 3% anaplastic. The 1-, 2-, and 5-year LC rates were 96%, 89%, and 82%, respectively. The median overall survival (OS) was 43 months, with 1-, 2-, and 5-year survival rates of 86%, 74%, and 44%, respectively. There was no correlation between the absolute biological equivalent dose (BED) and OS or LC. Patients with effective LC had a trend toward improved OS when compared to patients who had local failure: 68 versus 28 months (p = 0.07). In terms of toxicity, 5 vertebral compression fractures (2.8%) occurred, and only 1 case (0.6%) of greater than or equal to grade 3 toxicity (esophageal stenosis) was reported.

CONCLUSIONS

SSRS is a safe and effective treatment option with excellent LC and minimal toxicity for patients with metastatic thyroid cancer. No association with increased radiation dose or BED was found, suggesting that such patients can be effectively treated with reduced dose regimens.