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Purpose The single-session dose tolerance of the spinal nerves has been observed to be similar to that of the spinal cord in pigs, counter to the perception that peripheral nerves are more tolerant to radiation. This pilot study aims to obtain a first impression of the single-session dose-response of the brachial plexus using pigs as a model. Methods and Materials Ten Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiotherapy. A 2.5-cm length of the left-sided brachial plexus cords was irradiated. Pigs were distributed in 3 groups with prescription doses of 16 (n = 3), 19 (n = 4), and 22 Gy (n = 3). Neurologic status was assessed by observation for changes in gait and electrodiagnostic examination. Histopathologic examination was performed with light microscopy of paraffin-embedded sections stained with Luxol fast blue/periodic acid-Schiff and Masson's trichrome. Results Seven of the 10 pigs developed motor deficit to the front limb of the irradiated side, with a latency from 5 to 8 weeks after irradiation. Probit analysis of the maximum nerve dose yields an estimated ED50 of 19.3 Gy for neurologic deficit, but the number of animals was insufficient to estimate 95% confidence intervals. No motor deficits were observed at a maximum dose of 17.6 Gy for any pig. Nerve conduction studies showed an absence of sensory response in all responders and absent or low motor response in most of the responders (71%). All symptomatic pigs showed histologic lesions to the left-sided plexus consistent with radiation-induced neuropathy. Conclusions The single-session ED50 for symptomatic plexopathy in Yucatan minipigs after irradiation of a 2.5-cm length of the brachial plexus cords was determined to be 19.3 Gy. The dose-response curve overlaps that of the spinal nerves and the spinal cord in the same animal model. The relationship between the brachial plexus tolerance in pigs and humans is unknown, and caution is warranted when extrapolating for clinical use.

Introduction Paraspinal stereotactic body radiotherapy (SBRT) involves risks of severe complications. We evaluated the safety of the paraspinal SBRT program in a large academic hospital by applying failure modes and effects analysis. Methods The analysis was conducted by a multidisciplinary committee (two therapists, one dosimetrist, four physicists, and two radiation oncologists). The paraspinal SBRT workflow was segmented into four phases (simulation, treatment planning, delivery, and machine quality assurance (QA)). Each phase was further divided into a sequence of sub‐processes. Potential failure modes (PFM) were identified from each subprocess and scored in terms of the frequency of occurrence, severity and detectability, and a risk priority number (RPN). High‐risk PFMs were identified based on RPN and were studied for root causes using fault tree analysis. Results Our paraspinal SBRT process was characterized by eight simulations, 11 treatment planning, nine delivery, and two machine QA sub‐processes. There were 18, 29, 19, and eight PFMs identified from simulation, planning, treatment, and machine QA, respectively. The median RPN of the PFMs was 62.9 for simulation, 68.3 for planning, 52.9 for delivery, and 22.0 for machine QA. The three PFMs with the highest RPN were: previous radiotherapy outside the institution is not accurately evaluated (RPN: 293.3), incorrect registration between diagnostic magnetic resonance imaging and simulation computed tomography causing incorrect contours (273.0), and undetected patient movement before ExacTrac baseline (217.8). Remedies to the high RPN failures were implemented, including staff education, standardized magnetic resonance imaging acquisition parameters, and an image fusion process, and additional QA on beam steering. Conclusions A paraspinal SBRT workflow in a large clinic was evaluated using a multidisciplinary and systematic risk analysis, which led to feasible solutions to key root causes. Treatment planning was a major source of PFMs that systematically affect the safety and quality of treatments. Accurate evaluation of external treatment records remains a challenge.

BACKGROUND: Dynamic contrast agent–enhanced (DCE) perfusion MRI may help differentiate between nonneoplastic and malignant lesions in the spine. PURPOSE: To investigate the correlation between fractional plasma volume (V(p)), a parameter derived from DCE perfusion MRI, and histopathologic diagnosis for spinal lesions. MATERIALS AND METHODS: In this retrospective study, patients who underwent DCE perfusion MRI and lesion biopsy between May 2015 and May 2018 were included. Inclusion criteria were short time interval (

Background Over the last 2 decades, advances in systemic therapy have increased the expected overall survival for patients with cancer. It is unclear whether the same survival benefit has been conferred to patients requiring surgery for metastatic spinal disease. Objective To examine trends in postoperative survival over a 20-yr period for patients surgically treated for spinal metastatic disease. Methods Data were obtained for 1515 patients who underwent surgery for metastatic epidural spinal cord compression or tumor-related mechanical instability. Postoperative overall survival was calculated for all included patients using Kaplan-Meier methodology from date of surgery until death or last follow-up for those who were censored. Trends were analyzed using Cox proportional hazards modeling. Results Patients with renal, breast, lung, and colon cancers experienced a statistically significant improvement in survival over time based on the year of surgery (40%-100% improvement over the study period), whereas the overall survival trend for the entire cohort did not reach statistical significance (P = .12, median survival 0.71 yr, 95% CI 0.63-0.78). Patients presenting with synchronous metastatic disease had better survival compared to those presenting with metachronous disease (median overall survival: 0.94 vs 0.63 yr, respectively; log-rank P-value = .00001). Conclusion The postoperative survival among patients with spinal metastases has improved over the past 20 yr, particularly in patients with kidney, breast, lung, and colon tumors metastatic to the spine. The observed survival improvement emphasizes the need for long-term outcome consideration in treatment decisions for patients undergoing surgery for spinal metastatic tumors.

When treating solid tumor spine metastases, stereotactic high-dose-per-fraction radiation, given in a single fraction or in a hypofractionated approach, has proved to be a highly effective and safe therapeutic option for any tumor histology, in the setting of de novo therapy, as salvage treatment of local progression after previous radiation, and in the postoperative setting. There are variations in practice based on the clinical presentation, goals of therapy, as well as institutional preferences. As a biologically potent therapy, a thoughtful and careful attention to detail with patient selection, treatment planning, and delivery is crucial for treatment success.

Surgery alone provides suboptimal local control of spine and sacral chordomas. Radiotherapy (RT) may improve local control in patients undergoing surgery and be used as definitive-intent treatment in patients not undergoing surgery. Although conventional-dose RT is inadequate for these radioresistant tumors, newer techniques allow treatment of the tumor to higher, more effective doses while limiting spinal cord dose to safe levels. The best local control is achieved when RT is delivered in the primary setting; RT dose is a critical determinant of local control. RT should be considered for all spine and sacral chordoma patients.

OBJECTIVEThe current treatment of chordomas is associated with significant morbidity, high rates of local recurrence, and the potential for metastases. Stereotactic radiosurgery (SRS) as a primary treatment could reduce the need for en bloc resection to achieve wide or marginal margins. Spinal SRS outcomes support the exploration of SRS’s role in the durable control of these conventionally radioresistant tumors. The goal of the study was to evaluate outcomes of patients with primary chordomas treated with spinal SRS alone or in combination with surgery.METHODSClinical records were reviewed for outcomes of patients with primary chordomas of the mobile spine and sacrum who underwent single-fraction SRS between 2006 and 2017. Radiographic local recurrence-free survival (LRFS), overall survival (OS), symptom response, and toxicity were assessed in relation to the extent of surgery.RESULTSIn total, 35 patients with de novo chordomas of the mobile spine (n = 17) and sacrum (n = 18) received SRS and had a median post-SRS follow-up duration of 38.8 months (range 2.0–122.9 months). The median planning target volume dose was a 24-Gy single fraction (range 18–24 Gy). Overall, 12 patients (34%) underwent definitive SRS and 23 patients (66%) underwent surgery and either neoadjuvant or postoperative adjuvant SRS. Definitive SRS was selectively used to treat both sacral (n = 7) and mobile spine (n = 5) chordomas. Surgical strategies for the mobile spine were either intralesional, gross-total resection (n = 5) or separation surgery (n = 7) and for the sacrum en bloc sacrectomy (n = 11). The 3- and 5-year LRFS rates were 86.2% and 80.5%, respectively. Among 32 patients (91%) receiving 24-Gy radiation doses, the 3- and 5-year LRFS rates were 96.3% and 89.9%, respectively. The 3- and 5-year OS rates were 90.0% and 84.3%, respectively. The symptom response rate to treatment was 88% for pain and radiculopathy. The extent or type of surgery was not associated with LRFS, OS, or symptom response rates (p > 0.05), but en bloc resection was associated with higher surgical toxicity, as measured using the Common Terminology Criteria for Adverse Events (version 5.0) classification tool, than epidural decompression and curettage/intralesional resection (p = 0.03). The long-term rate of toxicity ≥ grade 2 was 31%, including 20% grade 3 tissue necrosis, recurrent laryngeal nerve palsy, myelopathy, fracture, and secondary malignancy.CONCLUSIONSHigh-dose spinal SRS offers the chance for durable radiological control and effective symptom relief with acceptable toxicity in patients with primary chordomas as either a definitive or adjuvant therapy.

Purpose For patients with long bone metastases who undergo orthopedic stabilization surgery followed by radiotherapy (RT), it is unclear what extent of hardware coverage by the radiation field is needed for optimal tumor control. Methods and Materials Long bone metastases treated with surgical intervention followed by radiation between August 2011 to May 2019 from a single institution were reviewed. Local recurrence, defined as any in-bone recurrence, was identified by chart review. Accompanying demographic and treatment characteristics were recorded. Statistical analysis to evaluate factors associated with tumor recurrence included univariate analysis, multivariate analysis, and propensity score matching. Results Among 138 patients with 145 long bone metastases undergoing postoperative RT with a median follow-up of 29.5 months, 36 bone metastases experienced a local recurrence. Most patients (92%) were treated with conventional RT and the median delivered dose was 30 Gy (interquarile range, 20-30 Gy). On univariate analysis, whole hardware RT field coverage and higher dose (biologically effective dose 10 ≥39 Gy) were associated with reduced local recurrence (0.44 hazard ratio [HR]; 95% confidence interval [CI], 0.22%-0.86%; P = .017; 0.5 HR; 95% CI, 0.26%-0.96%; P = .038, respectively). Covariates of time from surgery to RT start, histology of primary tumor (categorized as resistant vs sensitive), intramedullary hardware placement, reaming procedure, and margin status did not reach statistical significance. To adjust for confounding effects, we also conducted a propensity score matched analysis which confirmed that whole hardware coverage was statistically associated with a decreased risk of recurrence on the matched dataset (0.24 HR; 95% CI, 0.07%-0.84%; P = .026). Conclusions In this analysis of mostly patients undergoing conventional radiation, coverage of the whole hardware was associated with reduced local recurrence for patients with long bone metastases, consistent with prior reports. Investigation of approaches to further reduce local recurrence, such as preoperative stereotactic radiation, may be warranted.

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.

Purpose This prospective phase 3 randomized trial was designed to test whether ultra high single-dose radiation therapy (24 Gy SDRT) improves local control of oligometastatic lesions compared to a standard hypofractionated stereotactic body radiation therapy regimen (3 × 9 Gy SBRT). The secondary endpoint was to assess the associated toxicity and the impact of ablation on clinical patterns of metastatic progression. Methods and Materials Between November 2010 and September 2015, 117 patients with 154 oligometastatic lesions (≤5/patient) were randomized in a 1:1 ratio to receive 24 Gy SDRT or 3 × 9 Gy SBRT. Local control within the irradiated field and the state of metastatic spread were assessed by periodic whole-body positron emission tomography/computed tomography and/or magnetic resonance imaging. Median follow-up was 52 months. Results A total of 59 patients with 77 lesions were randomized to 24 Gy SDRT and 58 patients with 77 lesions to 3 × 9 Gy SBRT. The cumulative incidence of local recurrence for SDRT-treated lesions was 2.7% (95% confidence interval [CI], 0%-6.5%) and 5.8% (95% CI, 0.2%-11.5%) at years 2 and 3, respectively, compared with 9.1% (95% CI, 2.6%-15.6%) and 22% (95% CI, 11.9%-32.1%) for SBRT-treated lesions (P = .0048). The 2- and 3-year cumulative incidences of distant metastatic progression in the SDRT patients were 5.3% (95% CI, 0%-11.1%), compared with 10.7% (95% CI, 2.5%-18.8%) and 22.5% (95% CI, 11.1%-33.9%), respectively, for the SBRT patients (P = .010). No differences in toxicity were observed. Conclusions The study confirms SDRT as a superior ablative treatment, indicating that effective ablation of oligometastatic lesions is associated with significant mitigation of distant metastatic progression.

OBJECTIVEAs 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.METHODSThe 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.RESULTSEighty-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.CONCLUSIONSDurable 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.

OBJECTIVE: Dedifferentiated chordomas (DC) are genetically and clinically distinct from conventional chordomas (CC), exhibiting frequent SMARCB1 alterations and a more aggressive clinical course. We compared treatment and outcomes of DC and CC patients in a retrospective cohort study from a single, large-volume cancer center. METHODS: Overall, 11 DC patients were identified from 1994 to 2017 along with a cohort of 68 historical control patients with CC treated during the same time frame. Clinical variables and outcomes were collected from the medical record and Wilcoxon rank sum or Fisher exact tests were used to make comparisons between the two groups. Kaplan–Meier survival analysis and log-rank tests were used to compare DC and CC overall survival. RESULTS: DC demonstrated a bimodal age distribution at presentation (36% age 0–24; 64% age > 50). DC patients more commonly presented with metastatic disease than CC patients (36% vs. 3% p = 0.000). DC patients had significantly shorter time to local treatment failure after radiation therapy (11.1 months vs. 34.1 months, p = 0.000). The rate of distant metastasis following treatment was significantly higher in DC compared to CC (57% vs. 5%, p = 0.000). The median overall survival after diagnosis for DC was 20 months (95% CI 0–48 months) compared to 155 months (95% CI 94–216 months) for CC (p = 0.007). CONCLUSION: DC patients exhibit significantly higher rates of both synchronous and metachronous metastases, as well as shorter overall survival rates compared to conventional chordoma. The relatively poor survival outcomes with conventional therapies indicate the need to study targeted therapies for the treatment of DC.

Purpose This study was performed to determine the dose-related incidence of neuropathy from single-session irradiation of the C6-C8 spinal nerves using a pig model and to test the hypothesis that the spinal nerves and spinal cord have the same tolerance to full cross-sectional irradiation. Methods and Materials Twenty-five Yucatan minipigs received study treatment. Each animal underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 1.5-cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. Pigs were distributed into 5 groups with prescription doses of 16 (n = 7), 18 (5), 20 (5), 22 (5), or 24 (3) Gy with corresponding maximum nerve doses of 17.3, 19.5, 21.6, 24.1, and 26.2 Gy. The neurologic status of all animals was followed for approximately 52 weeks by serial electrodiagnostic examination and daily observation of gait. Histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff staining was performed on bilateral spinal nerves and the spinal cord. Results Marked gait change was observed in 15 of the 25 irradiated pigs. Affected animals presented with a limp in their left front limb, and electromyography demonstrated evidence of denervation in C6 and C7 innervated muscles. Probit analysis showed the ED50 for gait change after irradiation of the spinal nerves to be 19.7 Gy (95% confidence interval, 18.5-21.1). The latency for all responding pigs was 9 to 15 weeks after irradiation. All symptomatic pigs had demyelination and fibrosis in their irradiated nerves, whereas contralateral nerves and spinal cord were normal. Conclusions The ED50 for symptomatic neuropathy after full cross-sectional irradiation of the spinal nerves was found to be 19.7 Gy. The dose response of the C6-C8 spinal nerves is not significantly different from that of full cross-sectional irradiation of the spinal cord as observed in companion studies.

Beginning with basic stereotactic operative methods in neurosurgery, intraoperative navigation and image guidance systems have since become the norm in that field. Following the introduction of image guidance into spinal surgery, there has been a dramatic increase in its utilization across disciplines and pathologies. Spine tumor surgery encompasses a wide range of complex surgical techniques and treatment strategies. Similarly to deformity correction and trauma surgery, spine navigation holds potential to improve outcomes and optimize surgical technique for spinal tumors. Recent data demonstrate the applicability of neuro-navigation in the field of spinal oncology, particularly for spinal stabilization, maximizing extent of resection and integration of minimally invasive therapies. The rapid introduction of new, less invasive, and ablative surgical techniques in spine oncology coupled with the rising incidence of spinal metastatic disease make it imperative for spine surgeons to be familiar with the indications for and limitations of imaging guidance. Herein, we provide a practical, current concepts narrative review on the use of spinal navigation in three areas of spinal oncology: (a) extent of tumor resection, (b) spinal column stabilization, and (c) focal ablation techniques.

Purpose Island blocking occurs in single‐isocenter multiple‐target (SIMT) stereotactic radiotherapy (SRS) whenever targets share multi‐leaf collimator (MLC) leaf pairs. This study investigated the effect on plan quality and delivery, of reducing island blocking through collimator angle optimization (CAO). In addition, the effect of jaw tracking in this context was also investigated. Methods For CAO, an algorithm was created that selects the collimator angle resulting in the lowest level of island blocking, for each beam in any given plan. Then, four volume‐modulated arc therapy (VMAT) SIMT SRS plans each were generated for 10 retrospective patients: two CAO plans, with and without jaw tracking, and two plans with manually selected collimator angles, with and without jaw tracking. Plans were then assessed and compared using typical quality assurance procedures. Results There were no substantial differences between plans with and without CAO. Jaw tracking produced statistically significant reduction in low‐dose level parameters; healthy brain V10% and mean dose were reduced by 9.66% and 15.58%, respectively. However, quantitative values (108 cc for V10% and 0.35 Gy for mean dose) were relatively small in relation to clinical relevance. Though there were no statistically significant changes in plan deliverability, there was a notable trend of plans with jaw tracking having lower gamma analysis pass rates. Conclusion These findings suggest that CAO has limited benefit in VMAT SIMT SRS of 2–6 targets when using a low‐dose penalty to the healthy brain during plan optimization in Eclipse. As clinical benefits of jaw tracking were found to be minimal and plan deliverability was potentially reduced, a cautious approach would be to exclude jaw tracking in SIMT SRS plans.

Purpose/Objective(s) Leptomeningeal metastasis (LM) is associated with limited survival and treatment options for patients with solid tumor malignancies. While photon involved-field radiotherapy (IFRT) is effective for local palliation, it lacks durability. Craniospinal irradiation (CSI), in contrast, treats the entire central nervous system (CNS) compartment, thus potentially improving disease control. We previously reported the safety and tolerability of proton CSI (pCSI) in a completed phase IB study, and we are now reporting the mature survival outcomes of these patients. Materials/Methods We enrolled 24 patients with solid tumor LM to receive hypofractionated pCSI of 30 Gy (RBE) in 10 fractions in this phase I prospective trial between June 2018 and May 2019 (NCT03520504). The primary endpoint is dose-liming toxicity (DLT) within 1 month of treatment. Secondary endpoints, including time to CNS progression (CNS TTP), CNS progression-free survival (PFS), and overall survival (OS), were assessed using Kaplan-Meier analysis with median survival estimates and 95% confidence intervals (CI) reported. Correlations between cerebrospinal fluid (CSF) circulating tumor cells (CTCs) and survival outcomes were evaluated using Kaplan-Meier analysis. An optimal cutoff for CTCs was determined through maximally selected rank statistics using CNS PFS. Results Of the 24 patients enrolled, 3 did not complete treatment due to systemic disease progression and were excluded from this analysis. The majority of patients had metastatic lung (52%) and breast (33%) malignancies. The median age was 52 years (range 30-67 years) and the median Karnofsky performance status was 70 (range 60-90). The majority of patients had LM that progressed on other therapies prior to enrollment (57% vs. 43% of patients with newly diagnosed LM), and all patients with molecularly driven disease had CNS progression on small-molecule tyrosine kinase inhibitors prior to enrollment. Only 1 patient was censored at 24 months of follow-up, while 20 patients were followed until death with a median OS of 9 months (95% CI 6-22 months). The median CNS TTP was 8 months (95% CI 7-18 months), with 5 (24%) patients with durable CNS control for > 12 months after pCSI. The median CNS PFS was 7 months (95% CI 5-13 months). In the 18 patients with CSF CTCs evaluation at baseline, having a pre-pCSI CSF CTCs Conclusion We reported that pCSI is a safe treatment for patients with solid tumor LM. In this analysis, we demonstrated durable disease control and prolonged survival in some patients. Lower CSF CTCs at baseline, a potential biomarker of response, was associated with improved survival outcomes. An ongoing randomized phase II trial will determine the efficacy of pCSI compared to photon IFRT in patients with solid tumor LM.

Purpose/Objective(s) Optimal control of brain metastases (BM) from renal cell carcinoma (RCC) with stereotactic radiosurgery (SRS) is critical as tyrosine kinase inhibitors (TKI) and immunotherapy has significantly prolonged overall survival (OS), emphasizing the importance of minimizing potential morbidity from treatment-associated edema. Clinically, we have observed that RCC BM-associated edema seems to be less prominent when VEGF-targeted agents (VEGFi) such as axitinib are administered contemporaneously with SRS. We therefore investigated the role of VEGFi in intracranial edema reduction in pts treated with SRS. Materials/Methods We conducted a single institution retrospective analysis of all clear cell or unknown RCC pts with BM treated with SRS from 2013 onwards. We excluded non-clear cell RCC, lack of post-SRS imaging, and failure to complete SRS. The SRS plus VEGFi cohort was defined as VEGFi within 6 months of SRS. Volumetric data was obtained from SRS plans, edema was contoured on MR Brain T2 Flair, and paired t-test was performed. Multivariate analysis for OS performed with the Cox proportional hazards model. Results We identified 38 pts who received 78 courses of SRS + VEGFi and 18 pts who received 29 courses of SRS alone. For the SRS + VEGFi and SRS groups, median OS was 4.1y and 6.0y, median SRS dose was 21 Gy and 27 Gy with comparable pre-SRS steroid use of 52% and 57% (HR 0.51, P = 0.200) and baseline neurologic symptoms 50% and 74% (HR 0.943, P = 0.904), respectively. Among the SRS + VEGFi group, the mean intact tumor volume decreased from pre-SRS 1.89cc to 0.42cc at 6m post-SRS, compared to a decrease from 1.82cc to 1.28cc in the SRS group. Edema volume decreased from 17.65cc to 3.28cc in the SRS + VEGFi group with an increase from pre-SRS 5.78cc to 6.39cc at 6mo post-SRS in the SRS alone group (95% CI -3.67, 1.15, P = 0.154). Conclusion Despite similar pre-SRS steroid use and increased edema volume, VEGFi appeared to improve post-SRS edema with a notable reduction of neurological symptoms. Our data suggest VEGFi may offer symptomatic benefit for significant peritumoral edema even without overt disease progression, and that re-challenge or continuation of VEGFi with SRS should be considered in such patients.

Purpose/objective(s) Although clinical trial enrollment is critical to development of new cancer therapies, Materials/methods All patients enrolled on radiation oncology therapeutic clinical trials at community-based partner sites from Q2 2018 - Q1 2021 were included in this analysis. Guided by Expert Recommendation for Implementing Change (ERIC), strategies to increase trial enrollment were implemented prior to Q2 2020, and included: 1) altered incentive structure (per-patient cost paid to partner site, leaderboards), 2) building a coalition of physicians in metastatic disease, and 3) practice facilitation. An interrupted time series analysis included a two-tailed student's t-test to compare mean trial enrollments per quarter pre- and post-implementation. Protocol deviations were assessed in quality assurance (QA) review. Results Among 52 total patients enrolled in community-based, partner sites, 28 (54%) identify as Black or Hispanic. The number of clinical trials open to enrollment pre- and post-implementation was 5 vs. 8, respectively, while the number of patients enrolled was 6 vs. 46, respectively, representing an overall increase in mean number of quarterly patient enrollments from 1 to 11 (P Conclusion These implementation strategies were associated with increased therapeutic trial enrollment in community-based partner sites. With high variation in enrollment between physicians and prior research suggesting limited impact of site-level financial incentives, qualitative research will further investigate non-financial incentives and other facilitators to clinical trial enrollment within community-academic partnerships. Over-representation of minority patients further supports the benefit of enrolling patients on clinical trials in the community-based setting.

PURPOSE/OBJECTIVE(S) Carbon fiber composite (CFR-PEEK) implants have been shown to improve image quality in volumetric imaging compared with titanium (Ti). We perform a dosimetric comparison of proton and photon SBRT plans with Ti and CFR-PEEK implants for paraspinal SBRT treatments. MATERIALS/METHODS CT scans of a spine phantom embedded with CFR-PEEK and Ti implants were obtained. PTV and OAR contours for a 24 Gy single fraction plan were generated with dmax spinal cord < 14 Gy. Nine-field IMRT photon plans were optimized on both scans. Three-field pencil beam scanning (PBS) plans using multi-field optimization (MFO) were generated. Robust evaluation for 2 mm setup, ± 3.5% range and ± 10% material density override uncertainties were performed. To evaluate the MR image quality of the carbon fiber implants, an implant set was placed in a water phantom. Spine MRI imaging sequences were acquired at 1.5T and 3T and associated artifacts were evaluated. RESULTS Target V95 coverage statistics for all plans are shown in Table 1. Photon plans with CFR-PEEK vs. Ti implants were not significantly different. Target coverage goals and OAR constraints were met. When the CFR-PEEK optimized photon plan was recalculated on Ti CT, PTV V100% was reduced by 12.4%, demonstrating the dose perturbation induced by Ti implants. The MFO proton plans for both implant scenarios had lower coverage than the IMRT plans due to the sharper gradients on the IMRT plans. The PBS plan for CFR-PEEK had slightly better coverage than for Ti. Cord-constraint-free proton plans were generated to investigate how the cord constraint impacted the proton plan. Without the constraint, PTV V95% was 99.0% for CFR-PEEK and 94.9% for Ti plans. The increased coverage for CFR-PEEK plan suggests that the potential advantage of CFR-PEEK is masked by the tight cord constraints. In robustness analysis, no clear benefit was shown for range and setup uncertainties. However, advantage in target coverage robustness was seen under material density perturbation analysis. Specifically, the perturbed PTV V95% ranged from 88.7% to 88.4%. In contrast, for Ti plan, PTV V95% varied from 86.5% to 82.3% in perturbed scenarios. In MRI studies, no metal signal loss image artifacts were observed around the CFR-PEEK screws at either field strengths. Minor signal pile-up artifacts of < 5 mm can be seen on one side of the screw in high field 3 T studies but were negligible in 1.5 T studies. CONCLUSION For paraspinal SBRT, utilizing CFR-PEEK compared to Ti implants do not significantly affect plan quality for both PBS and IMRT. Proton plans are more robust for material composition uncertainties only. The largest advantage of CFR-PEEK vs. Ti will be in MR image quality improvements, which can translate to more accurate target delineations and improved follow-up image quality.

Purpose:Immune checkpoint inhibition (ICI) alone is not active in mismatch repair–proficient (MMR-P) metastatic colorectal cancer (mCRC), nor does radiotherapy alone result in objective systemic benefit. However, combined radiotherapy plus ICI can induce systemic antitumor immunity in preclinical and clinical models.Patients and Methods:In this single-center, phase II study, patients with chemotherapy-refractory MMR-P mCRC received durvalumab 1,500 mg plus tremelimumab 75 mg every 4 weeks plus radiotherapy. The primary endpoint was objective response rate (ORR) in nonirradiated lesions. Treatment and efficacy were correlated with peripheral immune cell profiles.Results:We enrolled 24 patients, and report outcomes after a median follow-up of 21.8 (range: 15.9–26.3) months. The ORR was 8.3% (2 patients) [95% confidence interval (CI), 1.0–27.0]. The median progression-free survival was 1.8 (95% CI, 1.7–1.9) months, median overall survival was 11.4 (95% CI, 10.1–17.4) months. Twenty five percent of patients (n = 6) had treatment-related grade 3–4 adverse events. We observed increased circulating CD8+ T lymphocyte activation, differentiation, and proliferation in patients with objective response.Conclusions:This combination of radiotherapy plus ICI study did not meet the prespecified endpoint criteria to be considered worthwhile for further study. However, rare instances of systemic immune augmentation and regression in nonirradiated lesions were observed (an abscopal response). Combination durvalumab and tremelimumab plus radiotherapy is feasible in MMR-P mCRC with a manageable safety profile. Further studies of novel immunotherapy combinations, and identification of biomarkers predictive of abscopal response are warranted.

Myositis of the paraspinal muscles can be a clinically significant side effect of spinal radiation surgery. This report describes the typical clinical scenario, relevant radiologic findings, treatment, and management with the best available evidence.

As a radioresistant lesion, chordoma has historically been considered a tumor that is not amenable to radiation therapy. However, beginning in the 1980s, evidence began to develop demonstrating that doses >70Gy could improve local control. Since that time, more advanced technologies have been developed that enable the delivery of therapeutic radiation doses while minimizing toxicities to adjacent tissues, such as the spinal cord and bowel. Evidence from series using these new focused modalities now suggests that radiation therapy in the adjuvant setting may improve local tumor control independent of surgical margin – the classic determinant of local progression-free survival. Evidence is also building that supports the use of focused photon radiation modalities in the neoadjuvant, definitive-intent, and salvage therapy roles. Here we review the new technologies and therapeutic paradigms that have enabled radiotherapy to become a routine part of the therapeutic plan for patients with chordoma of the vertebral column and sacrum.

Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic tumors. Radiotherapy (RT) is integral to LC treatment, and proton craniospinal irradiation (CSI) may make RT more effective by targeting the entire central nervous system (CNS) compartment. We evaluated outcomes in patients treated with proton CSI for LC. We identified 56 patients treated with proton CSI for LC between 2018 and 2020 at our institution. Data on patient demographics, disease and treatment history, cerebrospinal fluid circulating tumor cells (CSF CTCs), and gene alterations were collected. Kaplan Meier analysis and Cox regression models were used to compare correlates with CNS time to progression (TTP), CNS progression-free survival (PFS) and overall survival (OS). Most patients had non-small cell lung cancer (NSCLC, n=27, 48%) or breast cancer (n=21, 38%). The median age was 58 (30-77), and median KPS was 80 (60-90). The median RT dose was 30Gy (25-36). The median follow-up was 12 months (1-22), with 26 (46%) patients alive at the last follow-up. Of 35 (63%) patients who progressed, 6 (11%) progressed in the CNS, 13 (23%) progressed systemically, and 16 (29%) progressed in both. The median TTP, PFS and OS was 8 months (1-21), 6 months (1-21) and 8 months (1-22), respectively. No difference in PFS (7 vs. 6 months, p=0.6) and OS (8 vs. 7 months, p=0.3) was observed between patients with NSCLC and breast cancer. Of patients alive at 3 months, 79% showed stable or improved functional status after CSI. Decreased CSF CTCs immediately post CSI had significantly improved PFS (8 vs. 5 months with no CTC decrease, HR=0.3, p=0.02). Lastly, we identified genetic correlates with survival outcomes. Proton CSI appears to be a promising treatment for LC in select patients, resulting in prolonged CNS disease control and survival. A randomized trial is currently underway to assess its efficacy prospectively.

Purpose We sought to investigate the tumor control probability (TCP) of spinal metastases treated with stereotactic body radiation therapy (SBRT) in 1 to 5 fractions. Methods and Materials PubMed-indexed articles from 1995 to 2018 were eligible for data extraction if they contained SBRT dosimetric details correlated with actuarial 2-year local tumor control rates. Logistic dose-response models of collected data were compared in terms of physical dose and 3-fraction equivalent dose. Results Data were extracted from 24 articles with 2619 spinal metastases. Physical dose TCP modeling of 2-year local tumor control from the single-fraction data were compared with data from 2 to 5 fractions, resulting in an estimated α/β = 6 Gy, and this was used to pool data. Acknowledging the uncertainty intrinsic to the data extraction and modeling process, the 90% TCP corresponded to 20 Gy in 1 fraction, 28 Gy in 2 fractions, 33 Gy in 3 fractions, and (with extrapolation) 40 Gy in 5 fractions. The estimated TCP for common fractionation schemes was 82% at 18 Gy, 90% for 20 Gy, and 96% for 24 Gy in a single fraction, 82% for 24 Gy in 2 fractions, and 78% for 27 Gy in 3 fractions. Conclusions Spinal SBRT with the most common fractionation schemes yields 2-year estimates of local control of 82% to 96%. Given the heterogeneity in the tumor control estimates extracted from the literature, with variability in reporting of dosimetry data and the definition of and statistical methods of reporting tumor control, care should be taken interpreting the resultant model-based estimates. Depending on the clinical intent, the improved TCP with higher dose regimens should be weighed against the potential risks for greater toxicity. We encourage future reports to provide full dosimetric data correlated with tumor local control to allow future efforts of modeling pooled data.

Importance: Rising cancer incidence combined with improvements in systemic and local therapies extending life expectancy are translating into more patients with spinal metastases. This makes the multidisciplinary management of spinal metastases and development of new therapies increasingly important. Spinal metastases may cause significant pain and reduced quality of life and lead to permanent neurological disability if compression of the spinal cord and/or nerve root occurs. Until recently, treatments for spinal metastases were not optimal and provided temporary local control and pain relief. Spinal stereotactic ablative radiotherapy (SABR) is an effective approach associated with an improved therapeutic ratio, with evolving clinical application. Objective: To review the literature of spinal SABR for spinal metastases, discuss a multidisciplinary approach to appropriate patient selection and technical considerations, and summarize current efforts to combine spinal SABR with systemic therapies. Evidence Review: The MEDLINE database was searched to identify articles reporting on spinal SABR to September 30, 2018. Articles including clinical trials, prospective and retrospective studies, systematic reviews, and consensus recommendations were selected for relevance to multidisciplinary management of spinal metastases. Results: Fifty-nine unique publications with 5655 patients who underwent SABR for spinal metastases were included. Four comprehensive frameworks for patient selection were discussed. Spinal SABR was associated with 1-year local control rates of approximately 80% to 90% in the de novo setting, greater than 80% in the postoperative setting, and greater than 65% in the reirradiation setting. The most commonly discussed adverse effect was development of a vertebral compression fracture with variable rates, most commonly reported as approximately 10% to 15%. High-level data on the combination of SABR with modern therapies are still lacking. At present, 19 clinical trials are ongoing, mainly focusing on combined modality therapies, radiotherapy prescription dose, and oligometastic disease. Conclusions and Relevance: These findings suggest that spinal SABR may be an effective treatment option for well-selected patients with spinal metastases, achieving high rates of local tumor control with moderate rates of adverse effects. Optimal management should include review by a multidisciplinary care team.

OBJECTIVETo characterize the clinical outcomes when stereotactic body radiation therapy (SBRT) alone is used to treat high-grade epidural disease without prior surgical decompression, the authors conducted a retrospective cohort study of patients treated at the Memorial Sloan Kettering Cancer Center between 2014 and 2018. The authors report locoregional failure (LRF) for a cohort of 31 cases treated with hypofractionated SBRT alone for grade 2 epidural spinal cord compression (ESCC) with radioresistant primary cancer histology.METHODSHigh-grade epidural disease was defined as grade 2 ESCC, which is notable for radiographic deformation of the spinal cord by metastatic disease. Kaplan-Meier survival curves and cumulative incidence functions were generated to examine the survival and incidence experiences of the sample level with respect to overall survival, LRF, and subsequent requirement of vertebral same-level surgery (SLS) due to tumor progression or fracture. Associations with dosimetric analysis were also examined.RESULTSTwenty-nine patients undergoing 31 episodes of hypofractionated SBRT alone for grade 2 ESCC between 2014 and 2018 were identified. The 1-year and 2-year cumulative incidences of LRF were 10.4% (95% CI 0–21.9) and 22.0% (95% CI 5.5–38.4), respectively. The median survival was 9.81 months (95% CI 8.12–18.54). The 1-year cumulative incidence of SLS was 6.8% (95% CI 0–16.0) and the 2-year incidence of SLS was 14.5% (95% CI 0.6–28.4). All patients who progressed to requiring surgery had index lesions at the thoracic apex (T5–7).CONCLUSIONSIn carefully selected patients, treatment of grade 2 ESCC disease with hypofractionated SBRT alone offers a 1-year cumulative incidence of LRF similar to that in low-grade ESCC and postseparation surgery adjuvant hypofractionated SBRT. Use of SBRT alone has a favorable safety profile and a low cumulative incidence of progressive disease requiring open surgical intervention (14.5%).

Spinal meningiomas are the second most common intradural extramedullary tumor and are commonly encountered in neurosurgical practice. In the era of widespread access to magnetic resonance imaging (MRI), these tumors can be encountered incidentally, leaving patients and referring providers anxious for treatment recommendations. This chapter will systematically address considerations for diagnosis and management of spinal meningioma.

The advent of stereotactic radiosurgery (SRS) has revolutionized the management of brain metastases. In contrast to whole-brain radiation therapy, studies evaluating SRS outcomes in radioresistant histologies have consistently shown excellent 1-year local control rates ranging between 70% and 90%. The radiobiology of SRS is not completely understood, and the targets that modulate the therapeutic response to SBRT are the subject of ongoing debate. It is postulated that the greater biologically equivalent dose alone may not fully account for the superior local control rates observed with SRS.

Magnetic resonance imaging (MRI) with gadolinium contrast is the most useful imaging modality to visualize brain metastases. Metastases typically occur at the gray/white matter junction and can occur in any region of the brain. They may exert mass effect on surrounding structures that can produce clinical signs and symptoms, including hydrocephalus. While T1 and T2-weighted images are most commonly used in evaluating brain metastases, spoiled gradient recall echo and susceptibility-weighted imaging are also useful tools to evaluate brain metastases that are not contrast-enhancing, and perfusion imaging is useful for differentiating radiation necrosis. Metastatic disease to the meninges includes leptomeningeal and pachymeningeal disease, which is typically a poor prognostic sign. The 3D characteristics of post-contrast MRI and the various special sequences of MRI should all be used in the diagnosis and delineation of brain metastases.

Intraoperative radiotherapy (IORT) is the delivery of therapeutic radiation at the time of tumor resection to the area at highest risk of recurrence, which is becoming an increasingly important component in the optimal multidisciplinary management of metastatic and primary spinal disease. IORT can be accomplished using several techniques, including intraoperative electron or low-energy photon beam therapy, or using brachytherapy, which entails the placement of radioactive sources directly within a tumor or surgical cavity. These approaches allow for the delivery of high dose radiation in a focal manner, with relative sparing of nearby critical structures. This is of critical importance for the treatment of metastatic or primary spinal disease since the radiation tolerance of the spinal cord and cauda equina often limit the total amount of radiation that can be offered, especially in the setting of prior radiation. IORT is feasible in a variety of settings, including after surgical decompression and either before or after external beam radiotherapy. IORT may be an appropriate option for patients requiring re-treatment of challenging lesions such as radioresistant histologies or those with significant dural involvement. In this chapter, we will highlight various methods used to deliver intraoperative radiation for spinal malignancies and summarize key brachytherapy series to review its use in clinical scenarios.

BACKGROUND: Minimal access surgery (MAS) allows early return to systemic and radiation therapy in patients with cancer leading to its increasing utilization in the treatment of spinal metastases. Systematic examination of surgical indications resulted in the development of an algorithm for implementation of MAS in the treatment of spinal metastases. The object of this study was to evaluate a spine tumor MAS treatment algorithm using patient-reported outcomes in cancer patients undergoing treatment of spinal metastases. METHODS: A prospective cohort study. Patients who underwent spinal percutaneous instrumented stabilization with the addition of MAS cord or nerve root decompression and/or kyphoplasty when indicated at a tertiary cancer center between December 2013 and August 2016 were included. Validated patient reported outcome (PRO) measures including the Brief Pain Inventory (BPI) and the MD Anderson Symptom Inventory – Spine module (MDASI-sp) were utilized. PROs were collected and compared at baseline, 3 month and long-term follow up (4.5–12 months). RESULTS: Fifty-one patients were included. MAS resulted in a statistically significant decrease in the severity of pain, and improved activity, ability to work and enjoyment of life (P

Background The treatment of oligometastatic (≤5 metastases) spinal disease has trended toward ablative therapies, yet to the authors' knowledge little is known regarding the prognosis of patients presenting with oligometastatic spinal disease and the value of this approach. The objective of the current study was to compare the survival and clinical outcomes of patients with cancer with oligometastatic spinal disease with those of patients with polymetastatic (>5 metastases) disease. Methods The current study was an international, multicenter, prospective study. Patients who were admitted to a participating spine center with a diagnosis of spinal metastases and who underwent surgical intervention and/or radiotherapy between August 2013 and May 2017 were included. Data collected included demographics, overall survival, local control, and treatment information including surgical, radiotherapy, and systemic therapy details. Health-related quality of life (HRQOL) measures included the EuroQOL 5 dimensions 3-level questionnaire (EQ-5D-3L), the 36-Item Short Form Health Survey (SF-36v2), and the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ). Results Of the 393 patients included in the current study, 215 presented with oligometastatic disease and 178 presented with polymetastatic disease. A significant survival advantage of 90.1% versus 77.3% at 3 months and 77.0% versus 65.1% at 6 months from the time of treatment was found for patients presenting with oligometastatic disease compared with those with polymetastatic disease. It is important to note that both groups experienced significant improvements in multiple HRQOL measures at 6 months after treatment, with no differences in these outcome measures noted between the 2 groups. Conclusions The treatment of oligometastatic disease appears to offer a significant survival advantage compared with polymetastatic disease, regardless of treatment choice. HRQOL measures were found to improve in both groups, demonstrating a palliative benefit for all treated patients.

Background Conventional external beam radiation and stereotactic radiosurgery are common radiation techniques used to treat spinal tumors. Intraoperative brachytherapy (BT) may serve as an alternative when other options have been exhausted or as an adjunct in combination with other therapies. The objective of this study was to systematically review the literature on BT use in spinal tumor surgery. Methods PubMed and Embase databases were systematically queried for literature reporting the use of BT in the surgical treatment of spinal tumors. PRISMA guidelines were followed. A meta-analysis was performed. Results Of the 203 initial articles queried, 15 studies were included. Of the 370 total patients described, 78% were treated for spine metastases. Indications for BT included tumors refractory to previous treatments and inability to tolerate chemotherapy, radiation, and/or open surgery. Seed placement was the most common method of delivery (58%) compared with plaques (42%). BT was placed during an open procedure in 52%, and of the remaining percutaneous procedures, 47% were combined with cement augmentation. Tumor recurrence rates varied from 13% to 49%. Seven studies reporting visual analog scale scores reported significant improvement in pain control. Conclusions BT was used to treat metastatic disease in patients who failed previous therapies and could not tolerate open surgery or further therapy. This review summarizes the major findings in the available literature pertaining to patient background, indications, and outcomes. Spinal BT seems to be a viable option for spine tumor treatment and should be made available at treating centers.

Surgical decompression and stabilization followed by radiosurgery represents an effective method for local tumor control and neurologic preservation for patients with metastatic epidural spinal cord compression (MESCC). We have previously demonstrated improvement in health-related quality of life (HrQOL) after this combined modality treatment ("hybrid therapy").The current analysis focuses on delineation of patient-specific prognostic factors predictive of HrQOL change after combined surgery-stereotactic radiosurgery (SRS) treatment of MESCC.This is a prospective, single-center, cohort study.One hundred and eleven patients with MESCC who underwent separation surgery followed by SRS were included.Prognostic factors associated with improved patient-reported outcome (PRO) measures.Patient-reported outcome tools, that is, Brief Pain Inventory (BPI) and MD Anderson Symptom Inventory-Spine Tumor (MDASI-SP), both validated in the cancer population, were prospectively collected. Numeric prognostic factors were correlated with PRO measures using the Spearman rank correlation coefficient. Categorical prognostic factors were correlated with PRO measures using the Wilcoxon two-sample test (for two categories) or the Kruskal-Wallis test (for three or more categories). All statistical tests were two-sided with a level of significance.05 for correlation of prognostic factors with PRO constructs and a level of significance.0014 for correlation of prognostic factors with PRO items. Statistical analyses were done in SAS (version 9.4, Cary, NC, USA).One hundred and eleven patients were included in this analysis. Patients with lower preoperative Medical Research Council (MRC) motor scores experienced a greater decrease in symptom interference (BPI interference construct (p=.03) and individual functional measures including general activity (p=.001), walking (p=.001), and normal work (p=.006)). Lumbar location was associated with better outcomes than cervical or thoracic as noted on the BPI pain experience construct (p=.03) and MDASI-SP interference (p=.01) and core symptom (p=.002) constructs. Patients with American Spinal Injury Association (ASIA) scores of C or D benefit more than those with ASIA E on BPI interference construct (p=.04). Patients with higher Eastern Cooperative Oncology Group (ECOG) scores at presentation benefit more than those with low ECOG scores on MDASI-SP interference construct (p=.03). Women benefit more than men on BPI interference (p=.03) and pain experience (p=.04) constructs. Patients with prior spinal surgery at the current level of interest benefit less than those who are naïve surgical patients in MDASI-SP interference construct (p=.04).Delineation of patient characteristics associated with HrQOL improvement provides crucial information for patient selection, patient education, and setting treatment expectations. For patients with MESCC treated with hybrid therapy using surgery and radiosurgery, the presence of neurologic deficits and diminished performance status, lumbar tumor level, and female gender were associated with greater PRO improvement.

OBJECTIVESpinal stereotactic body radiation therapy (SBRT) has emerged as an attractive method to deliver high doses of radiation to oligometastatic spinal tumors with radioresistant histology. Because SBRT is a palliative therapy, attention to potential radiation toxicities is paramount when counseling patients. The objective of this study was to report radiation-induced myositis after SBRT, a previously undescribed complication.METHODSA total of 667 patients received 891 spine SBRT treatments (either 24 Gy in 1 fraction or 27 Gy in 3 fractions) from 2011 to 2016 and underwent retrospective review. Eleven patients were identified as having radiographic evidence of myositis following SBRT. Clinical and pathologic results were collected, including receipt of anti–vascular endothelial growth factor (VEGF) therapy, radiation dose, equivalent dose in 2-Gy fractions (EQD2), biologically effective dose (BED), and volume of muscle treated. Treatment toxicities were classified according to the Common Terminology Criteria for Adverse Events (CTCAE; version 4.03). Univariate statistical analyses were performed to evaluate the relationships between radiation fractionation schedule and myositis and between anti-VEGF therapy and myositis.RESULTSThe cumulative incidence of myositis was 1.9% at 1 year. The median of the mean dose administered to muscle with myositis was 17.5 Gy. The median EQD2 was 55.1 Gy, and the median BED was 82.7 Gy. The median time to the development of clinical symptoms was 1.4 months, while the median time to imaging evidence was 4.7 months. Two patients (18.2%) had CTCAE grade 3 complications. Single-fraction spine SBRT (HR 4.5, 95% CI 1.2–16.9; p = 0.027) was associated with increased risk of developing myositis whereas receipt of anti-VEGF therapy was not (HR 2.2, 95% CI 0.6–7.1; p = 0.2).CONCLUSIONSRadiation myositis following spinal radiosurgery is a rare but important complication. Single-fraction treatment schedules may be associated with increased risk of myositis but should be validated in a larger series.

Background and Purpose This study summarizes the cranial stereotactic radiosurgery (SRS) volumetric modulated arc therapy (VMAT) procedure at our institution. Materials and Methods Volumetric modulated arc therapy plans were generated for 40 patients with 188 lesions (range 2–8, median 5) in Eclipse and treated on a TrueBeam STx. Limitations of the custom beam model outside the central 2.5 mm leaves necessitated more than one isocenter pending the spatial distribution of lesions. Two to nine arcs were used per isocenter. Conformity index (CI), gradient index (GI) and target dose heterogeneity index (HI) were determined for each lesion. Dose to critical structures and treatment times are reported. Results Lesion size ranged 0.05–17.74 cm3 (median 0.77 cm3), and total tumor volume per case ranged 1.09–26.95 cm3 (median 7.11 cm3). For each lesion, HI ranged 1.2–1.5 (median 1.3), CI ranged 1.0–2.9 (median 1.2), and GI ranged 2.5–8.4 (median 4.4). By correlating GI to PTV volume a predicted GI = 4/PTV0.2 was determined and implemented in a script in Eclipse and used for plan evaluation. Brain volume receiving 7 Gy (V 7 Gy) ranged 10–136 cm3 (median 42 cm3). Total treatment time ranged 24–138 min (median 61 min). Conclusions Volumetric modulated arc therapy provide plans with steep dose gradients around the targets and low dose to critical structures, and VMAT treatment is delivered in a shorter time than conventional methods using one isocenter per lesion. To further improve VMAT planning for multiple cranial metastases, better tools to shorten planning time are needed. The most significant improvement would come from better dose modeling in Eclipse, possibly by allowing for customizing the dynamic leaf gap (DLG) for a special SRS model and not limit to one DLG per energy per treatment machine and thereby remove the limitation on the Y‐jaw and allow planning with a single isocenter.

OBJECTIVEThe 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.METHODSA 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.RESULTSOf 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.CONCLUSIONSIn 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.

Purpose/objective(s) Management of recurrent or new primary intracranial tumors in a previously irradiated area presents a significant challenge. For inoperable patients, reirradiation (re-RT) may provide the best chance for prolonged disease control. However, given concerns for excessive morbidity, re-RT with definitive doses (≥ 45 Gy) is not commonly prescribed. Given its dosimetric advantages over photon-based techniques, we hypothesize that intensity-modulated proton therapy (IMPT) may permit safer dose escalation in the re-RT setting. This study examined feasibility of definitive brain re-RT in a cohort of patients treated with IMPT. Materials/methods The electronic medical record of a pencil beam scanning-only proton center was queried for adult patients who developed in-field recurrence or new primary tumor for which they subsequently received definitive-dose (≥ 45 Gy) re-RT. Dosimetric and clinical characteristics were collected. Survival was examined using the Kaplan-Meier method. Toxicities were assessed using the Common Terminology Criteria for Adverse Events v.5.0. Results Between August 2019 and February 2021, 62 consecutive patients received intracranial re-RT with IMPT. Twelve (18%) were treated to ≥ 45 Gy and were included for analysis. Median age at the time of re-RT was 51.5 years, and 83% of patients had an Eastern Cooperative Oncology Group score of 0. The most common histologies were oligodendroglioma (n = 4), astrocytoma (n = 3), and meningioma (n = 3). Median time from prior radiation course to IMPT was 9.4 years (range, 3.6 - 42.0 years). IMPT was delivered with conventional fractionation in 92% and hypofractionation in 8% of cases. Median equivalent dose in 2 Gy fractions (EQD2) for initial course was 53.1 Gy. Median EQD2 for the re-RT course was 54.0 Gy. The entire re-RT course was completed as planned by 83% of patients. Patients received concurrent temozolomide (66%) or temozolomide plus bevacizumab plus nivolumab (8%). Dosimetric data from the initial course were available for 58% of patients. The median cumulative (initial radiation and re-RT combined) maximum EQD2 doses were 116.8 Gy to brain, 66.2 Gy to brainstem, 67.7 Gy to chiasm, 72.0 Gy to ipsilateral optic nerve, and 54.5 Gy to contralateral optic nerve. At a median follow-up of 5.4 months, 58.3% (n = 7) of patients developed grade 2 toxicities including fatigue (n = 6) and alopecia (n = 5). No grade ≥3 neurotoxicities were documented. Median progression free survival was 7 months; median overall survival was not reached. Conclusion Early results of our single-institution experience suggest a potential for safe intracranial re-RT with definitive-dose IMPT for select patients. Based on these findings, we are activating a prospective study to identify subsets of patients who are best fit for IMPT re-RT and formulate optimal dose regimens and normal tissue composite dose constraints. Author disclosure L. Maillie: None. S. Sharma: None. J.T. Yang: None. N. Ohri: Consultant; Merck, AstraZeneca. I.J. Choi: Employee; New York Proton Center. Travel Expenses; Varian; National Association of Proton Therapy, Proton Collaborative Group. Oversee and provide guidance for new and existing research protocols, ensure best practices for organization research endeavors.; Proton Collaborative Group. B.K. Yeh: None. R.H. Press: None. A. Chhabra: None. M.K. Garg: None. Y. Yamada: Consultant; University of Wollongong. Speaker's Bureau; Varian Medical Systems, BrainLab. Medical advisor; Chordoma Foundation. C.B. Simone: Employee; New York Proton Center. Honoraria; Varian Medical System, Novocure. Travel Expenses; Varian Medical System; Proton Collaborative Group (PCG), Annals of Palliative Medicine, American Society for Radiation Oncology. S. Lazarev: None.

Purpose/Objective(s) Local therapy for patients with non-spine bone metastases is evolving, with recent data suggesting that stereotactic body radiotherapy (SBRT) may improve pain response in the palliative setting. However, the rate of local salvage therapy (LST) after SBRT compared to conventional RT is unknown. We therefore characterized rates and risk factors for LST in patients with non-spine bone metastases. Materials/Methods We reviewed records of all courses of RT for non-spine bone metastases at our institution from 1/1/2016 to 12/31/2018. LST was defined as the first occurrence of either RT or surgery for progression to a bone metastasis following initial RT. Functions of the cumulative incidence of re-treatment were generated for each RT technique. We identified associations with various predictors using the Fine and Gray method for competing risk regression. Results Of the 1,754 patients included, 2,648 bone metastases were treated with RT and analyzed with a median follow up of 15 months (IQR = 6.4 – 25.0 months). 51% of episodes were multi-fraction EBRT, 10% were single fraction EBRT, and 39% were SBRT. Of the treated metastases, 120 (4.5%) episodes required LST (median time to LST = 6.2 months, range = 0.3-35.6 months), with a cumulative incidence at 6 and 12 months of 2.4% and 3.9%, respectively. Cumulative incidence of re-treatment at 6 months was 2.6% for SBRT, 3.5% for single-fraction conventional, and 2.1% for multi-fraction conventional regimens (P = 0.76). On multivariable analysis, younger age, higher Karnofsky performance status (KPS), and location of the metastasis in the pelvis had higher hazard of re-treatment (Table 1). There was no significant difference in hazard of LST among RT techniques (P = 0.44), nor was there a significant interaction between RT technique and radioresistant histology (P = 0.33). Conclusion In our large institutional cohort, the rate of LST was low, with no difference between RT techniques. Our results suggest that judicious selection of patients at high risk for eventual treatment failure (i.e., those with longer expected survival) for SBRT may reduce the rate of retreatment rate in the population. When patients are appropriately selected for single fraction conventional RT, such as those who are older or have poor KPS, rates of LST remain low. Further studies to validate our findings are warranted to help clinicians to select the appropriate treatment technique for patients with bone metastases.

Purpose/objective(s) Palliative radiation therapy (RT) can be an effective tool for bone metastases. NCCN guidelines recommend imaging every 3 months after RT for spine metastases (SM), yet no standard surveillance guidelines exist after RT for non-spine bone metastases (NSBM). We sought to evaluate factors associated with radiation oncology-specific follow-up after palliative RT. Materials/methods In a large single-institution retrospective cohort analysis, we identified all patients receiving RT for bone metastases by ICD-10 codes and RT prescription from 2017-2019. Demographic, clinical, and RT data were collected. Overall survival (OS) was calculated using Kaplan-Meier analysis. Factors associated with urgent care (UC) evaluation and radiation oncology follow-up were evaluated with multivariable logistic regression among patients surviving or followed to 3 months post-RT. Results Overall, 3082 patients (39% NSBM, 61% SM) received RT for bone metastases. Within 3 months of RT, 49% had radiation oncology follow-up, 79% underwent imaging, and 27% were seen in the UC. For patients with NSBM, follow-up CT was most common (55%) while for SM, MRI and CT were common (both 54%). Median OS was 10.0 months for SM (95% CI 8.9-11.0) and 13.5 months for NSBM (95% CI 11.5-15.5), with 1343 (71%) SM patients and 923 (77%) NSBM patients surviving to > = 3 months post-RT. Of the 2266 3-month survivors (41% NSBM, 59% SM), 1619 (71%) had radiation oncology follow-up, with higher performance status (OR 2.1, 95% CI 1.44-3.05) and younger patients ( Conclusion After RT for bone metastases, most patients had radiation oncology-specific surveillance, which was associated with younger age and improved performance status. Most patients survived to 3 months post-RT, with a substantial minority receiving a second RT course. Patients with NSBM had longer survival and different time-to-follow-up compared to SM, highlighting the need for further clarification on what the optimal follow-up should be for NSBM. Race was a predictor of UC visits, likely reflecting health disparities that require further investigation. These data support radiation oncology specific follow-up after RT, particularly among younger patients and those with higher performance status with specific attention to racial disparities.

Salvage brachytherapy is a treatment option for patients with locally recurrent prostate cancer after primary radiation therapy. We reviewed our experience using low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy to compare the outcome and toxicity profiles of each approach in the salvage brachytherapy setting.Ninety-eight patients with biopsy-proven locally recurrent prostate cancer who underwent salvage brachytherapy (LDR = 37; HDR = 61) following an initial course of definitive radiotherapy between 4/2003 and 4/2015 were retrospectively reviewed. All patients underwent salvage brachytherapy using LDR or HDR. Androgen deprivation therapy was used in 45% of the patients. Prostate-specific antigen (PSA) failure was determined using the Phoenix (nadir+2) definition. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4 and patient-reported questionnaires.Median followup was 31 months. The 3-year PSA relapse-free survival (RFS) was 60.1% (95% CI, 49.6-72.5%). There was no difference between LDR and HDR brachytherapy in terms of PSA RFS (p = 0.84 by log-rank test). On multivariate analysis, only prostate-specific antigen doubling time (PSADT)12 months was significantly associated with PSA relapse. The 3-year PSA RFS for patients with a PSADT12 months was 39% compared with 73% for PSADT ≥12 months (p = 0.002 by long-rank test). There were no statistically significant differences in toxicity between LDR and HDR brachytherapy. There was a higher peak in urinary symptoms in LDR patients; however by 24-36 months, most patients in both groups returned to baseline.Both LDR and HDR salvage brachytherapy are an excellent treatment options for appropriately selected patients with comparable outcome and toxicity. Patients with a PSADT 12 months seem to have worse outcomes.

Dose-volume tolerance of the spinal cord (SC) in spinal stereotactic radiosurgery (SRS) is difficult to define because radiation myelitis rates are low, and published reports document cases of myelopathy but do not account for the total number of patients treated at given dose-volume combinations who do not have myelitis. This study reports SC toxicity from single-fraction spinal SRS and presents a comprehensive atlas of the incidence of adverse events to examine dose-volume predictors.A prospective database of all patients undergoing single-fraction spinal SRS at our institution between 2004 and 2011 was reviewed. SC toxicity was defined by clinical myelitis with accompanying magnetic resonance imaging (MRI) signal changes that were not attributable to tumor progression. Dose-volume histogram (DVH) atlases were created for these endpoints. Rates of adverse events with 95% confidence limits and probabilities that rates of adverse events were2% and5% for myelitis were determined as functions of dose and absolute volume.Information about DVH and myelitis was available for 228 patients treated at 259 sites. The median follow-up time was 14.6 months (range, 0.1-138.3 months). The median prescribed dose to the planning treatment volume was 24 Gy (range, 18-24 Gy). There were 2 cases of radiation myelitis (rate r=0.7%) with accompanying MRI signal changes. Myelitis occurred in 2 patients, with Dmax13.33 Gy, and minimum doses to the hottest 0.1, 0.2, 0.5, and 1 cc were10.66, 10.9, and 8 Gy, respectively; however, both myelitis cases occurred below the 34th percentile for Dmax and there were 194 DVHs in total with Dmax13.33 Gy.A median SC Dmax of 13.85 Gy is safe and supports that a Dmax limit of 14 Gy carries a low1% rate of myelopathy. No dose-volume thresholds or relationships between SC dose and myelitis were apparent. This is the largest study examining dosimetric data and radiation-induced myelitis in de novo spine SRS.

Background Patient-reported outcomes (PRO) represent an important measure of cancer therapy effect. For patients with metastatic epidural spinal cord compression (MESCC), hybrid therapy using separation surgery and stereotactic radiosurgery preserves neurologic function and provides tumor control. There is currently a paucity of data reporting PRO after such combined modality therapy for MESCC. Delineation of hybrid surgery–radiosurgery therapy effect on PRO validates the hybrid approach as an effective therapy resulting in meaningful symptom relief. Patients and Methods Brief Pain Inventory (BPI) and MD Anderson Symptom Inventory—Spine Tumor (MDASI-SP), PROs validated in the cancer population, were prospectively collected. Patients with MESCC who underwent separation surgery followed by stereotactic radiosurgery were included. Separation surgery included a posterolateral approach without extensive cytoreductive tumor excision. A median postoperative radiosurgery dose of 2700 cGy was delivered. The change in PRO 3 months after the hybrid therapy represented the primary study outcome. Preoperative and postoperative evaluations were analyzed using the Wilcoxon signed-rank test for matched pairs. Results One hundred eleven patients were included. Hybrid therapy resulted in a significant reduction in the BPI items “worst” and “right now” pain (P < .0001), and in all BPI constructs (severity, interference with daily activities, and pain experience, P < .001). The MDASI-SP demonstrated reduction in spine-specific pain severity and interference with general activity (P < .001), along with decreased symptom interference (P < .001). Conclusions Validated PRO instruments showed that in patients with MESCC, hybrid therapy with separation surgery and radiosurgery results in a significant decrease in pain severity and symptom interference. These prospective data confirm the benefit of hybrid therapy for treatment of MESCC and should facilitate referral of patients with MESCC for surgical evaluation.

Patients with metastatic disease including polymetastatic, oligometastatic, and oligorecurrent spinal lesions have extended life expectancy secondary to improvements in systemic agents, and thus require durable local control of spine metastases. Stereotactic body radiotherapy (SBRT), which uses highly conformal treatment planning techniques coupled with image-guided technology, has enabled the safe delivery of tumor-ablative doses of radiotherapy. The NOMS decision framework has been developed as a tool to aid in the determination of the optimal treatment of spinal metastases, incorporating radiosurgery, separation surgery, stabilization techniques, and conventional radiation. Tumor radiosensitivity is critical in determining appropriateness of radiosurgery. In general, higher radiation doses provide significant, more durable tumor control, whether single-fraction or hypofractionated regimens are used. Spine SBRT can provide a high likelihood of durable tumor control with very low rates of serious toxicity, and careful attention should be given to dose constraints of organs at risk. Here, we review the indications for spine SBRT via the NOMS decision framework and provide practical information to the radiation oncologist regarding spine radiosurgery.

Background and purpose Hypofractionated conformal radiotherapy (hfCRT) is used for larger brain metastases or metastases near critical structures. We investigated hfCRT outcomes for newly diagnosed brain metastases. Materials and methods We identified 195 patients with 1–3 brain metastases who underwent 5×6Gy hfCRT for 231 lesions from 2007 to 2013. Associations among clinical factors, local control (LC), distant brain control (DC) and overall survival (OS) were tested using univariate and multivariate (MVA) Cox regression analysis and Kaplan–Meier method. Results Median follow-up was 12.8months. One hundred forty-three (62%) lesions were treated with hfCRT post-operatively, and 88 (38%) with definitive hfCRT. LC for all lesions was 83% at 1year. For lesions treated with post-operative hfCRT, tumor size (HR=4.7, p =0.04) and subtotal resection (HR=2.7, p =0.02) were predictive of local failure on MVA. For lesions ≥2.8cm in size, LC was 61% at 12months for lesions status-post subtotal resection, compared to 84% status-post gross total resection ( p =0.004). Extracranial disease presence was associated with worse DC (HR=1.8, p =0.008) and OS (HR=3.1, p Conclusions We showed 5×6Gy hfCRT provides acceptable LC at 1year for limited brain metastases. For large lesions not grossly resected, more aggressive strategies can be considered to improve LC.

To develop consensus contouring guidelines for postoperative stereotactic body radiation therapy (SBRT) for spinal metastases.Ten spine SBRT specialists representing 10 international centers independently contoured the clinical target volume (CTV), planning target volume (PTV), spinal cord, and spinal cord planning organ at risk volume (PRV) for 10 representative clinical scenarios in postoperative spine SBRT for metastatic solid tumor malignancies. Contours were imported into the Computational Environment for Radiotherapy Research. Agreement between physicians was calculated with an expectation minimization algorithm using simultaneous truth and performance level estimation with κ statistics. Target volume definition guidelines were established by finding optimized confidence level consensus contours using histogram agreement analyses.Nine expert radiation oncologists and 1 neurosurgeon completed contours for all 10 cases. The mean sensitivity and specificity were 0.79 (range, 0.71-0.89) and 0.94 (range, 0.90-0.99) for the CTV and 0.79 (range, 0.70-0.95) and 0.92 (range, 0.87-0.99) for the PTV), respectively. Mean κ agreement, which demonstrates the probability that contours agree by chance alone, was 0.58 (range, 0.43-0.70) for CTV and 0.58 (range, 0.37-0.76) for PTV (P.001 for all cases). Optimized consensus contours were established for all patients with 80% confidence interval. Recommendations for CTV include treatment of the entire preoperative extent of bony and epidural disease, plus immediately adjacent bony anatomic compartments at risk of microscopic disease extension. In particular, a "donut-shaped" CTV was consistently applied in cases of preoperative circumferential epidural extension, regardless of extent of residual epidural extension. Otherwise more conformal anatomic-based CTVs were determined and described. Spinal instrumentation was consistently excluded from the CTV.We provide consensus contouring guidelines for common scenarios in postoperative SBRT for spinal metastases. These consensus guidelines are subject to clinical validation.