Clinical Outcomes of Dose-Escalated Hypofractionated External Beam Radiation Therapy (5 Gy × 5 Fractions) for Spine Metastasis.

Purpose: The objective of this study was to determine the toxicities and outcomes of patients with spinal metastasis treated with external beam radiation therapy (EBRT) to 25 Gy in 5 fractions. Methods and Materials: Data were extracted from an institutional tumor registry for patients with spinal metastasis who were treated with EBRT to 25 Gy in 5 fractions to their spinal lesion(s). Cox regression and Kaplan-Meier analyses to determine local control and overall survival (OS) were employed. Results: Seventy-five patients with 86 total treated spinal metastatic tumors were identified. The median follow-up was 7 months. The median age was 66 years. Fifty-six patients (75.7%) experienced partial or complete pain relief for a median duration of 6 months (range, 1-33). Fifty-one (59.3%) cases were planned using intensity modulated radiation therapy while 19 (22.1%) employed 3-dimensional conformal radiation therapy and 16 (18.6%) cases used nonconformal radiation technique. Greater than 90% of cases had a point dose maximum to the spinal cord/cauda equina <27.5 Gy. No patient experienced treatment-related myelopathy. The most common toxicities were fatigue (23.3%), pain flare (14.0%), and nausea (8.1%). There were no grade 3 toxicities. One-year local control was 80.6%, and 1-year OS was 38.4%. Higher Karnofsky performance status (P = .001) and radiosensitive tumor histology (P = .014) were significant predictors for better OS. Conclusions: Our single-institutional retrospective analysis of patients with spinal metastasis suggested that palliative EBRT to 25 Gy in 5 fractions is safe, with a low toxicity profile and minimal risk for myelopathy with an achievable dose maximum to the spinal cord and cauda equina ≤27 Gy (equivalent total dose in 2-Gy fractions ≤50 Gy), and it may provide durable palliation and local control in cases where stereotactic body radiation therapy may not be indicated.

Personalized Treatment Selection Leads to Low Rates of Local Salvage Therapy for Bone Metastases.

PURPOSE: Local therapy for patients with nonspine bone metastases is evolving, with data supporting the use of single-fraction treatments, and more recently, showing possible benefit from stereotactic body radiation therapy (SBRT). However, the rate of local salvage therapy (LST) after each technique has not been characterized in real-world clinic settings where patients are selected at physician discretion. We examined rates of LST in patients with nonspine bone metastases. METHODS AND MATERIALS: We reviewed records of RT for nonspine bone metastases at our institution from January 1, 2016, to December 31, 2018. We defined LST as the first occurrence of RT or surgery for oncologic progression to a bone metastasis after initial RT. Cumulative incidence functions for retreatment were generated. We conducted multivariate analysis to identify variables associated with LST. RESULTS: A total of 1754 patients were analyzed, with median follow-up of 16.2 months (range, 0-36.8 months). Of all episodes of RT, 51.5% were multifraction external beam radiation therapy (EBRT), 7.0% were single-fraction EBRT, and 41.4% were SBRT. Altogether, 88 patients (5.0%) required LST, with an incidence at 6 months of 2.5%. Incidence of LST at 6 months was 2.1% for SBRT, 5.3% for single-fraction conventional regimens, and 2.4% for multifraction conventional regimens (P = .26). Patients of younger age, who had a higher Karnofsky performance status, and/or who had lesions in the pelvis had a higher risk of retreatment. CONCLUSIONS: In this large institutional cohort, the rate of LST was low, with no difference between RT techniques. The findings indicated that SBRT for patients at high risk for treatment failure may reduce the rate of retreatment overall. When treatment modality was selected based on patient characteristics, rates of LST were lower than when treatment was randomly selected.

Multidisciplinary Treatment of Non-Spine Bone Metastases: Results of a Modified Delphi Consensus Process.

Purpose: Local treatment for bone metastases is becoming increasingly complex. National guidelines traditionally focus only on radiation therapy (RT), leaving a gap in clinical decision support resources available to clinicians. The objective of this study was to reach expert consensus regarding multidisciplinary management of non-spine bone metastases, which would facilitate standardizing treatment within an academic-community partnership. Methods and Materials: A multidisciplinary panel of physicians treating metastatic disease across the Memorial Sloan Kettering (MSK) Cancer Alliance, including community-based partner sites, was convened. Clinical questions rated of high importance in the management of non-spine bone metastases were identified via survey. A literature review was conducted, and panel physicians drafted initial recommendation statements. Consensus was gathered on recommendation statements through a modified Delphi process from a full panel of 17 physicians from radiation oncology, orthopaedic surgery, medical oncology, interventional radiology, and anesthesia pain. Consensus was defined a priori as 75% of respondents indicating "agree" or "strongly agree" with the consensus statement. Strength of Recommendation Taxonomy was employed to assign evidence strength for each statement. Results: Seventeen clinical questions were identified, of which 11 (65%) were selected for the consensus process. Consensus was reached for 16 of 17 answer statements (94%), of which 12 were approved after Round 1 and additional 4 approved after Round 2 of the modified Delphi voting process. Topics included indications for referral to surgery or interventional radiology, radiation fractionation and appropriate use of stereotactic approaches, and the handling of systemic therapies during radiation. Evidence strength was most commonly C (n = 7), followed by B (n = 5) and A (n = 3). Conclusions: Consensus among a multidisciplinary panel of community and academic physicians treating non-spine bone metastases was feasible. Recommendations will assist clinicians and potentially provide measures to reduce variation across diverse practice settings. Findings highlight areas for further research such as pathologic fracture risk estimation, pre-operative radiation, and percutaneous ablation.

When Less Is More: The indications for MIS Techniques and Separation Surgery in Metastatic Spine Disease.

STUDY DESIGN: Systematic review. OBJECTIVE: The aim of this study was to review the techniques, indications, and outcomes of minimally invasive surgery (MIS) and separation surgery with subsequent radiosurgery in the treatment of patients with metastatic spine disease. SUMMARY OF BACKGROUND DATA: The utilization of MIS techniques in patients with spine metastases is a growing area within spinal oncology. Separation surgery represents a novel paradigm where radiosurgery provides long-term control after tumor is surgically separated from the neural elements. METHODS: PubMed, Embase, and CINAHL databases were systematically queried for literature reporting MIS techniques or separation surgery in patients with metastatic spine disease. PRISMA guidelines were followed. RESULTS: Of the initial 983 articles found, 29 met inclusion criteria. Twenty-five articles discussed MIS techniques and were grouped according to the primary objective: percutaneous stabilization (8), tubular retractors (4), mini-open approach (8), and thoracoscopy/endoscopy (5). The remaining 4 studies reported separation surgery. Indications were similar across all studies and included patients with instability, refractory pain, or neurologic compromise. Intraoperative variables, outcomes, and complications were similar in MIS studies compared to traditional approaches, and some MIS studies showed a statistically significant improvement in outcomes. Studies of mini-open techniques had the strongest evidence for superiority. CONCLUSIONS: Low-quality evidence currently exists for MIS techniques and separation surgery in the treatment of metastatic spine disease. Given the early promising results, the next iteration of research should include higher-quality studies with sufficient power, and will be able to provide higher-level evidence on the outcomes of MIS approaches and separation surgery. LEVEL OF EVIDENCE: N/A.

Stereotactic Body Radiotherapy for Spinal Metastases: What are the Risks and How Do We Minimize Them?

STUDY DESIGN: Systematic literature review. OBJECTIVES: To summarize the risks of 3 key complications of stereotactic body radiotherapy (SBRT) for spinal metastases, that is, radiation myelopathy (RM), vertebral compression fracture (VCF), and epidural disease progression, and to discuss strategies for minimizing them. SUMMARY OF BACKGROUND DATA: RM, VCF and epidural disease progression are now recognized as important risks following SBRT for spine metastases. It is unclear at this stage exactly how large these risks are and what strategies can be employed to minimize these risks. METHODS: A systematic review of the literature using MEDLINE and a review of the bibliographies of reviewed articles on SBRT for spinal metastases were conducted. RESULTS: The initial literature search revealed a total of 376 articles, of which 38 were pertinent to the study objectives. The risk of RM following SBRT was found to be dependent on the maximum dose to the spinal cord and estimated to be ≤5% if the recommended published thecal sac dose constraints are adhered to. The crude risk of VCF was 13.7% (range: 0.7%-40.5%), and, on average, 45% were surgically salvaged. It has been shown that the risk of VCF is dependent on several anatomic and tumor-related factors including the SBRT dose per fraction. The crude risk of local failure at 1 year was 21.4% (range: 12%-27%) of which 67% (range: 38%-96%) occurred within the epidural space. The grade of epidural disease has been shown to be associated with the risk of local failure. CONCLUSION: The risk of RM after spinal SBRT is low in particular if recommended dose metrics are adhered to. There is a significant risk of both VCF and epidural disease progression after spinal SBRT. These risks can potentially be minimized by identifying the risk factors for these complications, and performing careful radiotherapy and surgical planning. LEVEL OF EVIDENCE: 2.

Safety and Local Control of Radiation Therapy for Chordoma of the Spine and Sacrum: A Systematic Review.

STUDY DESIGN: Systematic literature review. OBJECTIVE: To assess the toxicity, common radiation doses, and local control (LC) rates of radiation therapy for chordoma of the spine and sacrum and identify the difference in LC and toxicity between adjuvant, salvage, and primary therapy using radiation. SUMMARY OF BACKGROUND DATA: Chordoma of the spine is typically a low-grade malignant tumor thought to be relatively radioresistant with a high rate of local recurrence and the potential for metastases. Improved results of modern radiation therapy in the treatment of chordoma support exploration of its role in the management of primary/de novo chordoma or recurrent chordoma. METHODS: We conducted a systematic literature review using PubMed and Embase databases to assess information available regarding the toxicity, LC rates, and overall survival (OS) rates for adjuvant, salvage, and primary radiation therapy for spinal and sacral chordoma. RESULTS: A total of 40 articles were reviewed. Evidence quality was low or very low. The highest rates of LC and OS were with early adjuvant RT for primary/de novo disease. Salvage RT for recurrent disease has very small cohorts and thus strong conclusions were not able be made. CONCLUSION: The use of pre- and/or post-operative photon image-guided radiotherapy (IGRT), proton or carbon ion therapy should be considered for patients undergoing surgery for the treatment of primary and recurrent chordomas in the mobile spine and sacrum, since these RT modalities may improve local control. Preoperative evaluation by the surgeon and radiation oncologist should be used to formulate a cohesive treatment plan.The use of photon IGRT or carbon ion therapy as the primary treatment of chordoma, when currently in its developmental stage, shows promise and requires clear delineation of toxicity profile and long-term local control. LEVEL OF EVIDENCE: 2.

Management of Locally Recurrent Chordoma of the Mobile Spine and Sacrum: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVE: To determine evidence-based guidelines for the management of locally recurrent spinal chordoma. SUMMARY OF BACKGROUND DATA: Chordoma of the spine is a low-grade malignant tumor with a strong propensity for local recurrence. Salvage therapy is challenging due to its relentless nature and refractoriness to adjuvant therapies. There are currently no guidelines regarding the best management of recurrent chordoma. METHODS: We combined the results of a systematic review with expert opinion to address the following research questions: (1) For locally recurrent chordoma of the spine without systemic disease, if surgery is planned, should en bloc resection be attempted if technically feasible with acceptable morbidity? (2) For locally recurrent chordoma without systemic disease, in which wide en bloc excision is not possible, what is the treatment of choice? (2) Should adjuvant or neoadjuvant radiation therapy be used in the treatment of locally recurrent chordoma? RESULTS: A total of nine surgical and seven radiation therapy articles met study criteria. Evidence quality was low or very low. Recurrent disease is associated with predominantly poor outcome, regardless of treatment modality. As for primary chordoma, resection with wide margins appears to confer an advantage with respect to local control, although this effect is attenuated in the setting of relapse. Postoperative radiation therapy likely reduces the rate of further relapse. CONCLUSION: (1) For locally recurrent chordoma of the spine without systemic disease, when surgery is planned, wide en bloc resection should be performed if technically feasible with acceptable morbidity. Strong recommendation, Low Quality of Evidence. (2) For locally recurrent chordoma without systemic disease, in which wide en bloc excision is not possible, partial resection is the treatment of choice. Weak recommendation, Very Low Quality of Evidence. (3) For the treatment of locally recurrent chordoma, high-dose conformal radiation therapy should be administered postoperatively to reduce the risk of further recurrence, and may be considered as a primary therapy. Strong recommendation, Very Low Quality of Evidence. LEVEL OF EVIDENCE: 2.

Fractures of the sacrum after chemoradiation for rectal carcinoma: incidence, risk factors, and radiographic evaluation.

PURPOSE: Sacral insufficiency fractures after adjuvant radiation for rectal carcinoma can present similarly to recurrent disease. As a complication associated with pelvic radiation, it is important to be aware of the incidence and risk factors associated with sacral fractures in the clinical assessment of these patients. METHODS AND MATERIALS: Between 1998 and 2007, a total of 582 patients with locally advanced rectal carcinoma received adjuvant chemoradiation and surgical excision. Of these, 492 patients had imaging studies available for review. Hospital records and imaging studies from all 492 patients were retrospectively evaluated to identify risk factors associated with developing a sacral insufficiency fracture. RESULTS: With a median follow-up time of 3.5 years, the incidence of sacral fractures was 7.1% (35/492). The 4-year sacral fracture free rate was 0.91. Univariate analysis showed that increasing age (≥60 vs. <60 years), female sex, and history of osteoporosis were significantly associated with shorter time to sacral fracture (P=.01, P=.004, P=.001, respectively). There was no significant difference in the time to sacral fracture for patients based on stage, radiotherapy dose, or chemotherapy regimen. Multivariate analysis showed increasing age (≥60 vs. <60 years, hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.22-5.13, P=.01), female sex (HR = 2.64, CI = 1.29-5.38, P=.008), and history of osteoporosis (HR = 3.23, CI = 1.23-8.50, P=.02) were independent risk factors associated with sacral fracture. CONCLUSIONS: Sacral insufficiency fractures after pelvic radiation for rectal carcinoma occur more commonly than previously described. Independent risk factors associated with fracture were osteoporosis, female sex, and age greater than 60 years.