Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection.

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Quality-of-life outcomes in metastatic spinal cord compression: findings from the SCORAD trial.

PURPOSE: This article reports detailed quality-of-life data including preferred and actual place of care from SCORAD, the only large prospective randomized trial in metastatic spinal cord compression (MSCC). METHODS: SCORAD compared 2 doses of radiotherapy in patients with MSCC: 8 Gy single fraction and 20 Gy in 5 fractions. In total, 686 patients were randomized, of whom 590 had Health-Related Quality of Life (HRQoL) data collected at baseline and at least 1 later time point. HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 supplemented with the QLU-C10D and data on place of care at weeks 1, 4, 8, and 12 postrandomization. Quality-of-Life Adjusted Survival was computed by multiplying Kaplan-Meier survival probabilities with the UK utility weights obtained from the QLU-C10D. RESULTS: Patients with a baseline physical functioning score of above 50 demonstrated a 28% reduction in the risk of death (hazard ratio [HR] = 0.72, 99% confidence interval [CI] = 0.54 to 0.95; P = .003). An increased risk of death was associated with fatigue (HR = 1.35, 99% CI = 1.03 to 1.76; P = .0040), dyspnea (HR = 1.61, 99% CI = 1.24 to 2.08; P < .001), and appetite loss (HR = 1.25, 99% CI = 0.99 to 1.59; P = .014). The preferred place of care for the majority was at home or with relatives (61%-74% across the 12 weeks) but achieved by only 53% at 8 weeks. CONCLUSIONS: Prolonged survival in patients with MSCC was associated with better HRQoL. More than 60% of patients preferred to be cared for at home or with relatives, but only half were able to achieve this. There was no difference in HRQoL between the multifraction and single-fraction groups. TRIAL REGISTRATION: ISRCTN97555949 and ISRCTN97108008.

The Perioperative Effects of Preoperative Radiotherapy in Metastatic Spinal Tumor Patients.

OBJECTIVE: Radiotherapy is one of the important treatment options for metastatic spinal tumors but is not the definite intervention in all cases, as there are patients who still require surgical treatment because of severe pain or neurologic events after this treatment. We evaluated the perioperative effects of preoperative radiotherapy in these cases as a future guide for surgeons on critical considerations in this period. METHODS: We included 328 patients in this study who had undergone decompression and fusion surgery for metastatic spinal tumors. Patients who underwent surgery with preoperative radiotherapy were designated as the radiotherapy group (group RT, n = 81), and cases of surgery without preoperative radiotherapy were assigned to the non-radiotherapy group (group nRT, n = 247). We compared the demographic, intraoperative, and postoperative factors between these 2 groups. RESULTS: In terms of intraoperative factors, statistically significant differences were evident in operation time, estimated blood loss, and transfusion (RT vs. nRT: 188.1 ± 80.7 minutes vs. 231.2 ± 106.1 minutes, 607.2 ± 532.7 mL vs. 830.1 ± 1324.7 mL, and 30.9% vs. 43.3%, P < 0.001, P < 0.031, and P < 0.048, respectively). With regard to postoperative factors, the incidence of infection, wound problems, and local recurrence were statistically higher in group RT (RT vs. nRT: 6.2% vs. 0.8%, 12.3% vs. 0.8%, 23.4% vs. 13.7%, P = 0.004, P < 0.001, and P = 0.038, respectively). CONCLUSIONS: Preoperative radiotherapy has the intraoperative advantages of reducing bleeding and shortening the operating time, but postoperative caution is needed because of the possibility of infection, wound problems, and local recurrence increases.

Dose averaged linear energy transfer optimization for large sacral chordomas in carbon ion therapy.

BACKGROUND: Carbon ion beams are well accepted as densely ionizing radiation with a high linear energy transfer (LET). However, the current clinical practice does not fully exploit the highest possible dose-averaged LET (LETd) and, consequently, the biological potential in the target. This aspect becomes worse in larger tumors for which inferior clinical outcomes and corresponding lower LETd was reported. PURPOSE: The vicinity to critical organs in general and the inferior overall survival reported for larger sacral chordomas treated with carbon ion radiotherapy (CIRT), makes the treatment of such tumors challenging. In this work it was aimed to increase the LETd in large volume tumors while maintaining the relative biological effectiveness (RBE)-weighted dose, utilizing the LETd optimization functions of a commercial treatment planning system (TPS). METHODS: Ten reference sequential boost carbon ion treatment plans, designed to mimic clinical plans for large sacral chordoma tumors, were generated. High dose clinical target volumes (CTV-HD) larger than 250 cm 3 $250 \,{\rm cm}^{3}$ were considered as large targets. The total RBE-weighted median dose prescription with the local effect model (LEM) was D RBE , 50 % = 73.6 Gy $\textrm {D}_{\rm RBE, 50\%}=73.6 \,{\rm Gy}$ in 16 fractions (nine to low dose and seven to high dose planning target volume). No LETd optimization was performed in the reference plans, while LETd optimized plans used the minimum LETd (Lmin) optimization function in RayStation 2023B. Three different Lmin values were investigated and specified for the seven boost fractions: L min = 60 keV / µ m $\textrm {L}_{\rm min}=60 \,{\rm keV}/{\umu }{\rm m}$ , L min = 80 keV / µ m $\textrm {L}_{\rm min}=80 \,{\rm keV}/{\umu }{\rm m}$ and L min = 100 keV / µ m $\textrm {L}_{\rm min}=100 \,{\rm keV}/{\umu }{\rm m}$ . To compare the LETd optimized against reference plans, LETd and RBE-weighted dose based goals similar to and less strict than clinical ones were specified for the target. The goals for the organs at risk (OAR) remained unchanged. Robustness evaluation was studied for eight scenarios ( ± 3.5 % $\pm 3.5\%$ range uncertainty and ± 3 mm $\pm 3 \,{\rm mm}$ setup uncertainty along the main three axes). RESULTS: The optimization method with L min = 60 keV / µ m $\textrm {L}_{\rm min}=60 \,{\rm keV}/{\umu }{\rm m}$ resulted in an optimal LETd distribution with an average increase of LET d , 98 % ${\rm {LET}}_{{\rm {d,}}98\%}$ (and LET d , 50 % ${\rm {LET}}_{{\rm {d,}}50\%}$ ) in the CTV-HD by 8.9 ± 1.5 keV / µ m $8.9\pm 1.5 \,{\rm keV}/{\umu }{\rm m}$ ( 27 % $27\%$ ) (and 6.9 ± 1.3 keV / µ m $6.9\pm 1.3 \,{\rm keV}/{\umu }{\rm m}$ ( 17 % $17\%$ )), without significant difference in the RBE-weighted dose. By allowing ± 5 % $\pm 5\%$ over- and under-dosage in the target, the LET d , 98 % ${\rm {LET}}_{{\rm {d,}}98\%}$ (and LET d , 50 % ${\rm {LET}}_{{\rm {d,}}50\%}$ ) can be increased by 11.3 ± 1.2 keV / µ m $11.3\pm 1.2 \,{\rm keV}/{\umu }{\rm m}$ ( 34 % $34\%$ ) (and 11.7 ± 3.4 keV / µ m $11.7\pm 3.4 \,{\rm keV}/{\umu }{\rm m}$ ( 29 % $29\%$ )), using the optimization parameters L min = 80 keV / µ m $\textrm {L}_{\rm min}=80 \,{\rm keV}/{\umu }{\rm m}$ . The pass rate for the OAR goals in the LETd optimized plans was in the same level as the reference plans. LETd optimization lead to less robust plans compared to reference plans. CONCLUSIONS: Compared to conventionally optimized treatment plans, the LETd in the target was increased while maintaining the RBE-weighted dose using TPS LETd optimization functionalities. Regularly assessing RBE-weighted dose robustness and acquiring more in-room images remain crucial and inevitable aspects during treatment.

Intraoperative radiotherapy combined with spinal stabilization surgery-a novel treatment strategy for spinal metastases based on a first single-center experiences.

INTRODUCTION: Current treatment of spinal metastases (SM) aims on preserving spinal stability, neurological status, and functional status as well as achieving local control. It consists of spinal surgery followed by radiotherapy and/or systemic treatment. Adjuvant therapy usually starts with a delay of a few weeks to prevent wound healing issues. Intraoperative radiotherapy (IORT) has previously been successfully applied during brain tumor, breast and colorectal carcinoma surgery but not in SM, including unstable one, to date. In our case series, we describe the feasibility, morbidity and mortality of a novel treatment protocol for SM combining stabilization surgery with IORT. METHODS: Single center case series on patients with SM. Single session stabilization by navigated open or percutaneous procedure using a carbon screw-rod system followed by concurrent 50 kV photon-IORT (ZEISS Intrabeam). The IORT probe is placed via a guide canula using navigation, positioning is controlled by IOCT or 3D-fluroscopy enabling RT isodose planning in the OR. RESULTS: 15 (8 female) patients (71 ± 10y) received this treatment between 07/22 and 09/23. Median Spinal Neoplastic Instability Score was 8 [7-10] IQR. Most metastasis were located in the thoracic (n = 11, 73.3%) and the rest in the lumbar (n = 4, 26.7%) spine. 9 (60%) patients received open, 5 (33%) percutaneous stabilization and 1 (7%) decompression only. Mean length of surgery was 157 ± 45 min. Eleven patients had 8 and 3 had 4 screws placed. In 2 patients radiotherapy was not completed due to bending of the guide canula with consecutive abortion of IORT. All other patients received 8 Gy isodoses at mdn. 1.5 cm [1.1-1.9, IQR] depth during 2-6 min. The patients had Epidural Spinal Cord Compression score 1a-3. Seven patients (46.7%) experienced adverse events including 2 surgical site infection (one 65 days after surgery). CONCLUSION: 50 kV photon IORT for SM and consecutive unstable spine needing surgical intervention is safe and feasible and can be a promising technique in selected cases.

Earlier Radiation Is Associated with Improved 1-Year Survival After Metastatic Spine Tumor Surgery.

OBJECTIVE: In patients undergoing metastatic spine surgery, we sought to 1) report time to postoperative radiation therapy (RT), 2) describe the predictive factors of time to postoperative RT, and 3) determine if earlier postoperative RT is associated with improved local recurrence (LR) and overall survival (OS). METHODS: A single-center retrospective cohort study was undertaken of all patients undergoing spine surgery for extradural metastatic disease and receiving RT within 3 months postoperatively between January 2010 and January 2021. Time to postoperative RT was dichotomized at <1 month versus 1-3 months. The primary outcomes were LR, OS, and 1-year survival. Secondary outcomes were wound complication, Karnofsky Performance Status, and modified McCormick Scale (MMS) score. Regression analyses controlled for age, body mass index, tumor size, preoperative RT, preoperative/postoperative chemotherapy, and type of RT. RESULTS: Of 76 patients undergoing spinal metastasis surgery and receiving postoperative RT within 3 months, 34 (44.7%) received RT within 1 month and 42 (55.2%) within 1-3 months. Patients with larger tumor size (ß = -3.58; 95% confidence interval [CI], -6.59 to -0.57; P = 0.021) or new neurologic deficits (ß = -16.21; 95% CI, -32.21 to -0.210; P = 0.047) had a shorter time to RT. No significant association was found between time to RT and LR or OS on multivariable logistic/Cox regression. However, patients who received RT between 1 and 3 months had a lower odds of 1-year survival compared with those receiving RT within 1 month (odds ratio, 0.18; 95% CI, 0.04-0.74; P = 0.022). Receiving RT within 1 month versus 1-3 months was not associated with wound complications (7.1% vs. 2.9%; P = 0.556) (odds ratio, 4.40; 95% CI, 0.40-118.0; P = 0.266) or Karnofsky Performance Status/modified McCormick Scale score. CONCLUSIONS: Spine surgeons, oncologists, and radiation oncologists should make every effort to start RT within 1 month to improve 1-year survival after metastatic spine tumor surgery.

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

BACKGROUND: The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS: This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS: Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS: Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months.

Changes in Spinal Instability After Conventional Radiotherapy for Painful Vertebral Bone Metastases.

OBJECTIVE: Precise assessment of spinal instability is critical before and after radiotherapy (RT) for evaluating the effectiveness of RT. Therefore, we retrospectively evaluated the efficacy of RT in spinal instability over a period of 6 months after RT, utilizing the spinal instability neoplastic score (SINS) in patients with painful spinal metastasis. We retrospectively evaluated 108 patients who received RT for painful vertebral metastasis in our institution. Mechanical pain at metastatic vertebrae, radiological responses of irradiated vertebrae, and spinal instability were assessed. Follow-up assessments were done at the start of and at intervals of 1, 2, 3, 4, and 6 months after RT, with the pain disappearing in 67%, 85%, 93%, 97%, and 100% of the patients, respectively. The median SINS were 8, 6, 6, 5, 5, and 4 at the beginning and after 1, 2, 3, 4, and 6 months of RT, respectively. Multivariate analysis revealed that posterolateral involvement of spinal elements (PLISE) was the only risk factor for continuous potentially unstable/unstable spine at 1 month. In conclusion, there was improvement of pain, and recalcification results in regaining spinal stability over time after RT although vertebral body collapse and malalignment occur in some irradiated vertebrae. Clinicians should pay attention to PLISE in predicting continuous potentially unstable/unstable spine.

Factors associated with non-completion of palliative radiotherapy for spinal metastasis in patients with terminal cancer: a retrospective study.

BACKGROUND: Predictors of non-completion of radiotherapy (RT) should be identified to determine the optimal RT dose. Therefore, this study aimed to explore factors associated with non-completion of palliative RT in patients with terminal cancer. METHODS: In this retrospective study, patients with terminal cancer who received RT (not including single-fraction RT) for relief of pain caused by spinal metastasis were categorized into complete and incomplete groups. Baseline characteristics, hematologic test data [e.g., total lymphocyte count (TLC)], performance status, palliative performance scale (PPS) score, psoas muscle index (PMI), Charlson comorbidity index, and age-adjusted Charlson comorbidity index of the patients were compared between the two groups. RESULTS: The complete group comprised 58 patients (median age: 68 years; female/male: 17/41; number of irradiation fractions: ≥2 to <10, 20 patients; 10, 34 patients; and >10, 4 patients), and the incomplete group comprised 9 patients (median age: 68 years; female/male: 3/6; number of irradiation fractions: ≥2 to <10, 2 patients; 10, 7 patients; and >10, 0 patient). The proportion of patient death within 1 week or 1 month was higher in the incomplete group than in the complete group. Compared with that in the incomplete group, TLC measured 1 week before RT (pre-TLC) and PMI recorded before RT were significantly higher in the complete group (P=0.013 and P=0.012, respectively). In multivariable analyses, pre-TLC was significantly associated with the incomplete group (P=0.048). Compared with the complete group, the incomplete group included several patients whose PPS scores rapidly decreased. CONCLUSIONS: Pre-TLC can predict non-completion of palliative RT in patients with terminal cancer.

40 Gray in 5 Fractions for Salvage Reirradiation of Spine Lesions Previously Treated With Stereotactic Body Radiotherapy.

BACKGROUND AND PURPOSE: A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed. METHODS: We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk. RESULTS: Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%. CONCLUSION: In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario.

Stereotactic body radiation therapy for spinal metastases: A new standard of care.

Advancements in systemic therapies for patients with metastatic cancer have improved overall survival and, hence, the number of patients living with spinal metastases. As a result, the need for more versatile and personalized treatments for spinal metastases to optimize long-term pain and local control has become increasingly important. Stereotactic body radiation therapy (SBRT) has been developed to meet this need by providing precise and conformal delivery of ablative high-dose-per-fraction radiation in few fractions while minimizing risk of toxicity. Additionally, advances in minimally invasive surgical techniques have also greatly improved care for patients with epidural disease and/or unstable spines, which may then be combined with SBRT for durable local control. In this review, we highlight the indications and controversies of SBRT along with new surgical techniques for the treatment of spinal metastases.

Utility of molecular markers in predicting local control specific to lung cancer spine metastases treated with stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: We report outcomes following spine stereotactic body radiotherapy (SBRT) in metastatic non-small cell lung cancer (NSCLC) and the significance of programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR) mutation and timing of immune check point inhibitors (ICI) on local failure (LF). MATERIALS AND METHODS: 165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was LF and secondary, overall survival (OS) and vertebral compression fracture (VCF). Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. RESULTS: The median follow-up and OS were: 13.0 months (range, 0.5-95.3 months) and 18.4 months (95% CI 11.4-24.6). 52.1% were male and 76.4% had adenocarcinoma. Of the 389 segments, 30.3% harboured an EGFR mutation and 17.0% were PD-L1 ≥ 50%. The 24 months LF rate in PD-L1 ≥ 50% vs PD-L1 < 50% was 10.7% vs. 38.0%, and in EGFR-positive vs. negative was 18.1% vs. 30.0%. On MVA, PD-L1 status of ≥ 50% (HR 0.32, 95% CI 0.15-0.69, p = 0.004) significantly predicted for lower LF compared to PD-L1 < 50%. Lower LF trend was seen with ICI administration peri and post SBRT (HR 0.41, 95% CI 0.16-1.05, p = 0.062). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84-5.85, p < 0.0001) and ECOG ≥ 2 (HR 1.87, 95% CI 1.16-3.02, p = 0.011) significantly predicted for worse OS and absence of baseline VCF predicted for lower VCF rate (HR 0.20, 95% CI 0.10-0.39, p < 0.0001). CONCLUSION: We report a significant association of PD-L1 ≥ 50% status on improved LC rates from spine SBRT in NSCLC patients.

Assessment of minimum target dose as a predictor of local failure after spine SBRT.

OBJECTIVES: Metastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. METHODS: Spine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20-24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27-36 Gy and 21-24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. RESULTS: 522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3-54.4). The cumulative incidence of local failure was 10.5 % (7.4-13.4) at 1 year and 16.3 % (12.6-19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 - 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6-9.4) vs. 14.2 % (8.3-19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). CONCLUSIONS: Spine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14-15.3 Gy with single fraction SBRT is recommended whenever possible.

Stereotactic Body Radiation Therapy for Sacral Metastases: Deviation From Recommended Target Volume Delineation Increases the Risk of Local Failure.

PURPOSE: Although spine stereotactic body radiation therapy (SBRT) is considered a standard of care in the mobile spine, mature evidence reporting outcomes specific to sacral metastases is lacking. Furthermore, there is a need to validate the existing sacral SBRT international consensus contouring guidelines to define the optimal contouring approach. We report mature rates of local failure (LF), adverse events, and the effect of contouring deviations in the largest experience to date specific to sacrum SBRT. METHODS AND MATERIALS: Consecutive patients who underwent sacral SBRT from 2010 to 2021 were retrospectively reviewed. The primary endpoint was magnetic resonance imaging-based LF with a focus on adherence to target volume contouring recommendations. Secondary endpoints included vertebral compression fracture and neural toxicity. RESULTS: Of the 215 sacrum segments treated in 112 patients, most received 30 Gy/4 fractions (51%), 24 Gy/2 fractions (31%), or 30 Gy/5 fractions (10%). Sixteen percent of segments were nonadherent to the consensus guideline with a more restricted target volume (undercontoured). The median follow-up was 21.4 months (range, 1.5-116.9 months). The cumulative incidence of LF at 1 and 2 years was 18.4% and 23.1%, respectively. In those with guideline adherent versus nonadherent contours, the LF rate at 1 year was 15.1% versus 31.4% and at 2 years 18.8% versus 40.0% (hazard ratio [HR], 2.5; 95% CI, 1.4-4.6; P = .003), respectively. On multivariable analysis, guideline nonadherence (HR, 2.4; 95% CI, 1.3-4.7; P = .008), radioresistant histology (HR, 2.4; 95% CI, 1.4-4.1; P < .001), and extraosseous extension (HR, 2.5; 95% CI, 1.3-4.7; P = .005) predicted for an increased risk of LF. The cumulative incidence of vertebral compression fracture was 7.1% at 1 year and 12.3% at 2 years. Seven patients (6.3%) developed peripheral nerve toxicity, of whom 4 had been previously radiated. CONCLUSIONS: Sacral SBRT is associated with high efficacy rates and an acceptable toxicity profile. Adhering to consensus guidelines for target volume delineation is recommended to reduce the risk of LF.

Stereotactic Radiosurgery for Patients with Spinal Metastases from Thyroid Cancer: A 20-Year Experience.

OBJECTIVE: Primary thyroid cancer metastasizing to the spine portends poor survival and low quality of life. Current management strategies continue to evolve. This single-institution retrospective study analyzes outcomes after spinal stereotactic radiosurgery for patients with spinal metastases from thyroid cancer. METHODS: Nineteen patients (median age: 64.5 years) were treated with stereotactic radiosurgery (SRS) for spinal primary thyroid metastases (40 metastases, 47 vertebral levels) between 2003 and 2023. Nineteen (47.5%) lesions had epidural involvement and 20 (50%) lesions were classified as potentially unstable or unstable via the Spinal Instability Neoplastic Score. The median tumor volume per lesion was 33 cc (range: 1.5-153). The median single fraction prescription dose was 20 Gy (range: 12-23.5). RESULTS: The median follow-up period was 15 months (range: 2-40). Five (12.8%) lesions locally progressed at a median of 9 months (range: 4-26) after SRS. The 1-, 2-, and 3-year local tumor control rates per lesion were 90.4%, 83.5%, and 75.9%, respectively. On univariate analysis, age at SRS >70 years (P = 0.05, hazard ratio: 6.86, 95% confidence interval: 1.01-46.7) was significantly correlated with lower rates of local tumor control. The median overall survival was 35 months (range: 2-141). The 1-, 2-, and 3-year overall survival rates were 73.7%, 50.4%, and 43.2%, respectively. For 33 lesions initially associated with pain, patients reported pain improvement (22 lesions, 66.7%), stability (10 lesions, 30.3%), and worsening (1 lesion, 3.0%) after SRS. One patient developed dysphagia 4 months after SRS treatment. CONCLUSIONS: SRS can be utilized as an effective and safe primary and adjuvant treatment option for primary thyroid metastases to the spine.

Efficacious patient-specific QA for Vertebra SBRT using a high-resolution detector array SRS MapCHECK: AAPM TG-218 analysis.

PURPOSE: Patient-specific quality assurance (PSQA) for vertebra stereotactic body radiation therapy (SBRT) presents challenges due to highly modulated small fields with high-dose gradients between the target and spinal cord. This study aims to explore the use of the SRS MapCHECK® (SRSMC) for vertebra SBRT PSQA. METHODS: Twenty vertebra SBRT treatment plans including prescriptions 20 Gy/1 fraction and 24 Gy/2 fractions were selected for each of Millennium (M)-Multileaf Collimator (MLC), and high-definition (HD)-MLC. All 40 plans were measured using Gafchromic EBT3 film (film) and SRSMC, using the StereoPHAN phantom. Plan complexity was assessed using modulation complexity score (MCS), edge metric (EM) (mm-1), modulation factor (MU/cGy), and average leaf pair opening (ALPO) (mm) and its correlation with gamma-pass rate was investigated. The high dose gradient between the target and the spinal cord was analyzed for film and SRSMC and compared against the treatment planning system (TPS). Applying the methodology proposed by AAPM TG-218, action and tolerance values specific to the SRSMC for vertebra SBRT were determined for ß values ranging from 5 to 8. RESULTS: Film and SRSMC gamma-pass rates showed no correlation (p > 0.05). A moderate negative correlation (R = -0.57, p = 0.01) is present between EM and SRSMC 3%/1 mm gamma-pass rate for HD-MLC plans. Both film and SRSMC accurately measured high dose gradients between the target and the spinal cord (R2 > 0.86, p ≤ 0.05). Notably, dose-gradient of HD-MLC plans is 22% steeper and has a smaller standard deviation to M-MLC plans (p ≤ 0.05). Applying TG-218, the film tolerance limit was 96% with action limit 95% for 5%/1 mm (ß = 6) and for the SRSMC tolerance limit was 97% with an action limit of 96% for 4%/1 mm (ß = 6). CONCLUSION: Our findings suggest that universal TG-218 limits may not be suitable for vertebra SBRT PSQA. This study demonstrates that SRSMC is a viable tool for vertebra SBRT PSQA, supported by TG-218 implementation of process-based tolerance and action limits.

Influence of dose calculation algorithms on the helical diode array using volumetric-modulated arc therapy for small targets.

BACKGROUND: For patient-specific quality assurance (PSQA) for small targets, the dose resolution can change depending on the characteristics of the dose calculation algorithms. PURPOSE: This study aimed to evaluate the influence of the dose calculation algorithms Acuros XB (AXB), anisotropic analytical algorithm (AAA), photon Monte Carlo (pMC), and collapsed cone (CC) on a helical diode array using volumetric-modulated arc therapy (VMAT) for small targets. MATERIALS AND METHODS: ArcCHECK detectors were inserted with a physical depth of 2.9 cm from the surface. To evaluate the influence of the dose calculation algorithms for small targets, rectangular fields of 2×100, 5×100, 10×100, 20×100, 50×100, and 100×100 mm2 were irradiated and measured using ArcCHECK with TrueBeam STx. A total of 20 VMAT plans for small targets, including the clinical sites of 19 brain metastases and one spine, were also evaluated. The gamma passing rates (GPRs) were evaluated for the rectangular fields and the 20 VMAT plans using AXB, AAA, pMC, and CC. RESULTS: For rectangular fields of 2×100 and 5×100 mm2, the GPR at 3%/2 mm of AXB was < 50% because AXB resulted in a coarser dose resolution with narrow beams. For field sizes > 10×100 mm2, the GPR at 3%/2 mm was > 88.1% and comparable for all dose calculation algorithms. For the 20 VMAT plans, the GPRs at 3%/2 mm were 79.1 ± 15.7%, 93.2 ± 5.8%, 94.9 ± 4.1%, and 94.5 ± 4.1% for AXB, AAA, pMC, and CC, respectively. CONCLUSION: The behavior of the dose distribution on the helical diode array differed depending on the dose calculation algorithm for small targets. Measurements using ArcCHECK for VMAT with small targets can have lower GPRs owing to the coarse dose resolution of AXB around the detector area.

Re-irradiation spine stereotactic body radiotherapy following high-dose conventional radiotherapy for metastatic epidural spinal cord compression: a retrospective study.

PURPOSE:  We aimed to evaluate the efficacy and safety of re-irradiation stereotactic body radiation therapy (SBRT) in patients with metastatic epidural spinal cord compression (MESCC) following high-dose conventional radiotherapy. MATERIALS AND METHODS:  Twenty-one patients met the following eligibility criteria: with an irradiation history of 50 Gy2 equivalent dose in 2-Gy fractions (EQD2) or more, diagnosed MESCC in the cervical or thoracic spines, and treated with re-irradiation SBRT of 24 Gy in 2 fractions between April 2018 and March 2023. Prior treatment was radiotherapy alone, not including surgery. The primary endpoint was a 1-year local failure rate. Overall survival (OS) and treatment-related adverse events were assessed as the secondary endpoints. Since our cohort includes one treatment-related death (TRD) of esophageal perforation, the cumulative esophageal dose was evaluated to find the dose constraints related to severe toxicities. RESULTS:  The median age was 68, and 14 males were included. The primary tumor sites (esophagus/lung/head and neck/others) were 6/6/7/2, and the median initial radiotherapy dose was 60 Gy2 EQD2 (range: 50-105 Gy2, 60-70/ > 70 Gy2 were 11/4). Ten patients underwent surgery followed by SBRT and 11 SBRT alone. At the median follow-up time of 10.4 months, 17 patients died of systemic disease progression including one TRD. No radiation-induced myelopathy or nerve root injuries occurred. Local failure occurred in six patients, with a 1-year local failure rate of 29.3% and a 1-year OS of 55.0%. Other toxicities included five cases of vertebral compression fractures (23.8%) and one radiation pneumonitis. The cumulative esophageal dose was recommended as follows: Dmax < 203, D0.035 cc < 187, and D1cc < 167 (Gy3 in biological effective dose). CONCLUSION:  Re-irradiation spine SBRT may be effective for selected patients with cervical or thoracic MESCC, even with high-dose irradiation histories. The cumulative dose assessment across the original and re-irradiated esophagus was recommended to decrease the risk of severe esophageal toxicities.

Definitive single fraction spine stereotactic radiosurgery for metastatic sarcoma: Simultaneous integrated boost is associated with high tumor control and low vertebral fracture risk.

INTRODUCTION: Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS). MATERIALS AND METHODS: A retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective 95 % confidence intervals (CI). RESULTS: 70 patients with 100 lesions underwent SSRS for SSM. Median follow-up was 19.3 months (IQR 7.7-27.8). Median age was 55 years (IQR42-63). Median GTV and CTVs were 14.5 cm3 (IQR 5-32) and 52.7 cm3 (IQR 29.5-87.5) respectively. Median GTV prescription dose and biologically equivalent dose (BED) [α/ß = 10] was 24 Gy and 81.6 Gy respectively. 85 lesions received 24 Gy to the GTV. 27 % of patients had Bilsky 1b or greater disease. 16 of 100 lesions recurred representing a crude local failure rate of 16 % with a median time to failure of 10.4 months (IQR 5.7-18) in cases which failed locally. 1-year actuarial local control (LC) was 89 %. Median overall survival (OS) was 15.3 months (IQR 7.7-25) from SSRS. Every 1 Gy increase in GTV absolute minimum dose (DMin) across the range (5.8-25 Gy) was associated with a reduced risk of local failure (HR = 0.871 [95 % CI 0.782-0.97], p = 0.009). 9 % of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). CONCLUSION: This study represents one of the most homogenously treated and the largest cohorts of patients with SSM treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates.