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PDF - 63KB, Prospective studies combining ipilimumab and radiation therapy for patients with unresectable and/or metastatic melanoma.

PDF - 59KB, Frequency of immune-related adverse events (irAEs) in the present study and in a previous study.

Ipilimumab and radiotherapy are commonly used to treat unresectable and metastatic melanoma. Results from preclinical studies and case reports suggest a biologic interaction between these two treatments. To understand the clinical implications of the interaction, we carried out a retrospective study reviewing records of patients treated with ipilimumab and radiotherapy for melanoma at our institution between 2005 and 2011. The review included details of treatment, response, adverse events (AE), and overall survival (OS). Twenty-nine patients underwent 33 courses of non-brain radiotherapy between their first and last dose of ipilimumab. Immune-related AEs (ir-AEs) were observed in 43% of patients receiving ipilimumab at 10 mg/kg and in 22% of patients receiving 3 mg/kg; the frequency of ir-AEs was not significantly different compared with previous studies of ipilimumab alone. Radiotherapy-related AEs were significantly more common in patients receiving higher doses of radiation. Palliation of symptoms was reported by 77% of patients after radiotherapy. Median OS was 9 and 39 months in patients receiving radiotherapy during induction and maintenance with ipilimumab, respectively. In this retrospective study, concurrent ipilimumab and radiotherapy was neither associated with higher than expected rates of AEs nor did it abrogate palliative effects of radiotherapy or survival benefits of ipilimumab. Further studies to prospectively explore the efficacy of this therapeutic combination are warranted. Cancer Immunol Res; 1(2); 92–98. ©2013 AACR.

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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.

Radiation treatment summary

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.

Chordomas are rare tumors of the embryologic spinal cord remnant. They are locally aggressive and typically managed with surgery and either adjuvant or neoadjuvant radiation therapy. However, there is great variability in practice patterns including radiation type and fractionation regimen, and limited high-level data to drive decision making. The purpose of this manuscript was to summarize the current literature specific to radiotherapy in the management of spine and sacral chordoma and to provide practice recommendations on behalf of the Spine Tumor Academy. A systematic review of the literature was performed using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) approach. Medline and Embase databases were utilized. The primary outcome measure was the rate of local control. A detailed review and interpretation of eligible studies is provided in the manuscript tables and text. Recommendations were defined as follows: (1) consensus: approved by >75% of experts; (2) predominant: approved by >50% of experts; (3) controversial: not approved by a majority of experts. Expert consensus supports dose escalation as critical in optimizing local control following radiation therapy for chordoma. In addition, comprehensive target volumes including sites of potential microscopic involvement improve local control compared with focal targets. Level I and high-quality multi-institutional data comparing treatment modalities, sequencing of radiation and surgery, and dose/fractionation schedules are needed to optimize patient outcomes in this locally aggressive malignancy.

PURPOSE: Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted community-based partner sites with a high potential to improve diverse population accrual. This study evaluates the effectiveness of a set of implementation strategies for increasing overall community-based enrollment and the resulting proportional enrollment of Hispanic patients on trials on the basis of availability in community-based partner sites. METHODS: An interrupted time series analysis evaluating implementation strategies was conducted from April 2018 to September 2021. Descriptive analysis ofHispanic enrollment on investigator-initiated randomized therapeutic radiation trials open at community-based sites was compared with those open only at themain academic center. RESULTS: Overall, 84 patients were enrolled in clinical trials in the MSK Alliance, of which 48 (56%) identified as Hispanic. The quarterly patient enrollment pre- vs postimplementation increased from 1.39 (95% CI, –3.67 to 6.46) to 9.42 (95% CI, 2.05 to 16.78; P5 .017). In the investigator-initiated randomized therapeutic radiation trials open in the MSK Alliance, Hispanic representation was 11.5% and 35.9% in twometastatic trials and 14.2% in a proton versus photon trial. Inmatched trials open only at the main academic center, Hispanic representation was 5.6%, 6.0%, and 4.0%, respectively. CONCLUSION: A combination of practice-level and physician-level strategies implemented at community-based partner sites was associated with increased clinical trial enrollment, which translated to improved Hispanic representation. This supports the role Q:2 of strategic community-academic partnerships in addressing disparities in clinical trial enrollment.

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.

The management of spinal metastatic renal cell carcinoma (mRCC) is controversial regarding extent of resection and radiation dosing. OBJECTIVE: To determine outcomes in patients treated with hybrid therapy (separation surgery plus adjuvant stereotactic body radiation therapy [SBRT]) for mRCC. METHODS: A retrospective study of a prospectively collected cohort of patients undergoing hybrid therapy for mRCC between 2003 and 2017 was performed. SBRT was delivered as high-dose single-fraction, high-dose hypofractionated, or low-dose hypofractionated. Extent of disease, clinical and operative outcomes, and complications data were collected, and associations with overall survival (OS) and progression-free survival were determined. RESULTS: Ninety patients with mRCC with high-grade epidural spinal cord compression (ESCC grades 2 and 3) were treated. Metastases were widespread, oligometastatic, and solitary in 56%, 33%, and 11% of patients, respectively. SBRT delivered was high-dose single-fraction, high-dose hypofractionated, and low-dose hypofractionated in 24%, 56%, and 20% of patients, respectively. The 1-yr cumulative incidence of major complications was 3.4% (95% confidence interval [CI]: 0.0%-7.2%). The median follow-up was 14.2 mo for the entire cohort and 38.3 mo for survivors. The 1-yr cumulative incidence of progression was 4.6% (95% CI: 0.2%-9.0%), which translates to a local control rate of 95.4% (95% CI: 91.0%-99.8%) 1 yr after surgery. The median OS for the cohort was 14.8 mo. CONCLUSION: These data support the use of hybrid therapy as a safe and effective strategy for the treatment of renal cell spine metastases.

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.

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.

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.

Tumor cure with conventional fractionated radiotherapy is 65%, dependent on tumor cell-autonomous gradual buildup of DNA double-strand break (DSB) misrepair. Here we report that single-dose radiotherapy (SDRT), a disruptive technique that ablates more than 90% of human cancers, operates a distinct dual-target mechanism, linking acid sphingomyelinase-mediated (ASMase-mediated) microvascular perfusion defects to DNA unrepair in tumor cells to confer tumor cell lethality. ASMase-mediated microcirculatory vasoconstriction after SDRT conferred an ischemic stress response within parenchymal tumor cells, with ROS triggering the evolutionarily conserved SUMO stress response, specifically depleting chromatin-associated free SUMO3. Whereas SUMO3, but not SUMO2, was indispensable for homology-directed repair (HDR) of DSBs, HDR loss of function after SDRT yielded DSB unrepair, chromosomal aberrations, and tumor clonogen demise. Vasoconstriction blockade with the endothelin-1 inhibitor BQ-123, or ROS scavenging after SDRT using peroxiredoxin-6 overexpression or the SOD mimetic tempol, prevented chromatin SUMO3 depletion, HDR loss of function, and SDRT tumor ablation. We also provide evidence of mouse-to-human translation of this biology in a randomized clinical trial, showing that 24 Gy SDRT, but not 3×9 Gy fractionation, coupled early tumor ischemia/reperfusion to human cancer ablation. The SDRT biology provides opportunities for mechanism-based selective tumor radiosensitization via accessing of SDRT/ASMase signaling, as current studies indicate that this pathway is tractable to pharmacologic intervention.

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) 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) 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.

Background Leptomeningeal metastasis (LM) involves cerebrospinal fluid (CSF) seeding of tumor cells. Proton craniospinal irradiation (pCSI) is potentially effective for solid tumor LM. We evaluated whether circulating tumor cells (CTCs) in the CSF (CTCCSF), blood (CTCblood), and neuroimaging correlate with outcomes after pCSI for LM. Methods We describe a single-institution consecutive case series of 58 patients treated with pCSI for LM. Pre-pCSI CTCs, the change in CTC post-pCSI (Δ CTC), and MRIs were examined. Central nervous system progression-free survival (CNS-PFS) and overall survival (OS) from pCSI were determined using Kaplan Meier analysis, Cox proportional-hazards regression, time-dependent ROC analysis, and joint modeling of time-varying effects and survival outcomes. Results The median CNS-PFS and OS were 6 months (IQR: 4–9) and 8 months (IQR: 5–13), respectively. Pre-pCSI CTCCSF < 53/3mL was associated with improved CNS-PFS (12.0 vs 6.0 months, P < .01). Parenchymal brain metastases (n = 34, 59%) on pre-pCSI MRI showed worse OS (7.0 vs 13 months, P = .01). Through joint modeling, CTCCSF was significantly prognostic of CNS-PFS (P < .01) and OS (P < .01). A Δ CTC-CSF≥37 cells/3mL, the median Δ CTC-CSF at nadir, showed improved CNS-PFS (8.0 vs 5.0 months, P = .02) and further stratified patients into favorable and unfavorable subgroups (CNS-PFS 8.0 vs 4.0 months, P < .01). No associations with CTCblood were found. Conclusion We found the best survival observed in patients with low pre-pCSI CTCCSF and intermediate outcomes for patients with high pre-pCSI CTCCSF but large Δ CTC-CSF. These results favor additional studies incorporating pCSI and CTCCSF measurement earlier in the LM treatment paradigm.

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.

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.

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.

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.

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.

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.

The spine is the third most common site of metastatic disease after the lungs and liver [1–2]. Several imaging modalities exist for the evaluation of epidural disease, namely computed tomography (CT) and magnetic resonance imaging (MRI). CT myelography (CTM) involves the injection of contrast material into the cerebrospinal fluid prior to imaging and requires ionizing radiation. Though previously widely used, CTM has steadily fallen out of favor to MRI at many institutions and in some cases, is used alone in radiation therapy planning. MRI is notable for its non-invasive nature, excellent visualization of soft tissues, and lack of exposure to ionizing radiation. CTM, however, can provide improved visualization of bony structures and is more resistant than MRI to geometric distortion and patient motion due to the rapid acquisition of images [3]. Additionally, CTM can be used in patients with contraindications to MRI and can also provide a direct correlation of electron density to doses used for radiation therapy planning [4]. With recent advances in radiation therapy, including intensity-modulated and image-guided radiation therapy, which aim to improve tumor targeting thereby sparing normal tissue, precise tumor localization for treatment planning often requires the use of CT integrated with MRI [5–7]. A previous study comparing CTM and MRI in the evaluation of degenerative disease in the cervical spine found that MRI was superior in its reliability for assessing the degree of nerve root compression while CTM provided greater reliability in the assessment of bony lesions and foraminal stenosis [8]. Other studies focusing on the lumbar spine also found that CTM provided greater reliability and reproducibility in the assessment of the extent of lumbar stenosis than did MRI [9] and that MRI underestimated the degree of spinal root compression in the lumbar spine [10]. While both imaging modalities have complementary advantages, studies to date have not investigated a composite evaluation of spinal epidural disease. Furthermore, given the limitations of MRI, it has not been studied whether there is merit in continuing to use CTM to complement MRI for radiation therapy planning. This study is the first to investigate whether axial and sagittal projections of the spinal epidural space using both T1 and T2-weighted MRI compared to CTM produce compatible levels of inter- and intra-rater reliability in measuring the extent of epidural disease by neuroradiologists trained in both imaging modalities. The results of this study will be useful in determining whether CTM should continue to be used in conjunction with MRI when evaluating spinal metastases and planning radiation therapy.

PURPOSE: The presence of brain metastases (BM) in patients with non-seminomatous germ cell tumor (NSGCT) is associated with poor prognosis. While radiation therapy (RT) is an important treatment for patients with NSGCT BM, there is a paucity of data on the optimal regimen. We sought to investigate the impact of RT on clinical outcomes in patients with NSGCT BM. METHODS: Patients with NSGCT BM who received RT at our institution from 2002–2017 were included. Sixty-three consecutive patients were identified. Clinical factors associated with intracranial control (ICC) and overall survival (OS) were evaluated using Cox regression analysis and Kaplan Meier method. RESULTS: Median age was 31 years and number of BM was 3. Fifteen patients presented with BM at diagnosis, while 48 developed BM at a median time of 8.4 months from diagnosis. At a median follow-up of 3.6 years, ICC and OS were 39.7% and 30.1%. On multivariate analysis, ICC (hazard ratio [HR]=0.93, p=0.03) and OS (HR=0.93, p=0.005) were both significantly associated with biologically effective dose (BED) of RT. The 4-year OS of patients who received BED