Conventional External Beam Radiation Research Articles

Stereotactic Body Radiation Therapy vs. Conventional External Beam Radiation Therapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis of Randomized Trials

<h3>Purpose/Objective(s)</h3> The magnitude of benefit and toxicity of stereotactic body radiation therapy (SBRT) compared with conventional external beam radiation therapy (cEBRT) in treating symptomatic bone metastases is unclear due to the conflicting results from randomized controlled trials (RCTs). We performed a systematic review and meta-analysis to compare the efficacy and safety of SBRT and cEBRT in patients with previously unirradiated painful bone metastases. <h3>Materials/Methods</h3> We searched various databases and major oncologic conference proceedings from inception to Oct 2021 for RCTs comparing SBRT with cEBRT for previously unirradiated painful bone metastases. The outcomes of interest were efficacy (overall and complete pain response rates, local progression, overall survival (OS) and quality of life (QoL)) and safety (post-irradiation fractures, pain flares and radiation myelopathy). We assessed the methodologic quality of individual trials using the revised Cochrane risk-of-bias (RoB2) tool. We performed one-stage individual patient data meta-analysis using multilevel logistic regression model. Sensitivity analyses were conducted using two-stage frequentist and Bayesian meta-analyses. We adopted Synthesis Without Meta-analysis (SWiM) approach to summarize adverse events and quality of life outcomes. We assessed the certainty of the evidence for the efficacy outcomes using GRADE approach. <h3>Results</h3> Six RCTs including 894 patients were identified. Five of the included trials had low risk of bias. There was no significant difference in overall pain response rates at 3 months between SBRT and cEBRT (odd ratio (OR), 1.10; 95% confidence interval (CI), 0.84-1.44; P, 0.48; GRADE, moderate certainty). SBRT significantly improved complete pain response rates at 3 months (OR, 3.38; 95% CI, 1.88-6.07; P< 0.01; GRADE, high certainty) and reduced local progression rates (OR, 0.15; 95% CI, 0.04-0.53; P< 0.01; GRADE, high certainty), compared to cEBRT. Sensitivity analyses showed consistent findings. SBRT was associated with a modest increase in pain flare rates, compared to cEBRT. There were no significant differences between the two groups in OS, post-irradiation fracture and radiation myelopathy. The QoL was similar, except for improved perception of financial burden with SBRT at 4 weeks. <h3>Conclusion</h3> Among the patients with previously unirradiated symptomatic bone metastases, SBRT significantly improved complete but not overall pain response rates at 3 months and delayed local progression without adversely impacting on the quality of life and overall survival, compared to cEBRT. SBRT was associated with a modest increase in the pain flare rates, compared to cEBRT.

Dose-Escalated 2-Fraction Spine Stereotactic Body Radiation Therapy: 28 Gy Versus 24 Gy in 2 Daily Fractions

Stereotactic body radiation therapy (SBRT) for spine metastases improves pain response rates compared with conventional external beam radiation therapy; however, the optimal fractionation schedule is unclear. We report local control and toxicity outcomes after dose-escalated 2-fraction spine SBRT. A prospectively maintained institutional database of over 600 patients and 1400 vertebral segments treated with spine SBRT was reviewed to identify those prescribed 28 or 24 Gy in 2 daily fractions. The primary endpoint was magnetic resonance imaging based local failure (LF), and secondary endpoints included overall survival and vertebral compression fracture (VCF). A total of947 treated vertebral segments in 482 patients were identified, of which 301 segments in 159 patients received 28 Gy, and 646 segments in 323 patients received 24 Gy in 2 fractions. Median follow-up per patient was 23.5 months, and median overall survival was 49.1 months. In the 28 Gy cohort, the 6-, 12-, and 24-month cumulative incidences of LF were 3.5%, 5.4%, and 11.1%, respectively, versus 6.0%, 12.5%, and 17.6% in the 24 Gy cohort, respectively (P=.008). On multivariable analysis, 24 Gy (hazard ratio [HR], 1.525; 95% confidence interval, 1.039-2.238; P=.031), paraspinal disease extension (HR, 1.422; 95% confidence interval, 1.010-2.002; P=.044), and epidural extension in either radioresistant or radiosensitive histologies (HR, 2.117 and 1.227, respectively; P=.003) were prognostic for higher rates of LF. Risk of VCF was 5.5%, 7.6%, and 10.7% at 6, 12, and 24 months, respectively, and was similar between cohorts (P=.573). Spinal malalignment (P < .001), baseline VCF (P=.003), junctional spine location (P=.030), and greater minimum dose to 90% of planning target volume were prognostic for higher rates of VCF. Dose escalation to 28 Gy in 2 daily fractions was associated with improved local control without increasing the risk of VCF. The 2-year local control rates are consistent with those predicted by the HypofractionatedTreatment Effects in the Clinic spine tumor control probability model, and these data will inform a proposed dose escalation randomized trial.

Stereotactic Body Radiotherapy vs. Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

<h3>Purpose/Objective(s)</h3> As the superiority of stereotactic body radiotherapy (SBRT) over conventional external beam radiotherapy (cEBRT) remains controversial for pain palliation, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). <h3>Materials/Methods</h3> A systematic review of literature was conducted in PubMed on January 22, 2022, which included prospective RCTs published to date. The inclusion criteria were as follows: (i) RCT comparing SBRT with cEBRT for bone metastases, and (ii) endpoint including pain response. The primary outcome of interest was the overall pain response (OR) rate of bone metastases at 3 months in intention-to-treat analysis. As a subgroup analysis, the analyses on OR were performed in spinal metastases. Pooling of effect sizes across studies was conducted using random-effects models in a meta-analysis of risk ratios. <h3>Results</h3> After 1,246 articles were screened, seven articles comprising 964 patients (522 and 442 patients in the SBRT and cEBRT arms, respectively) met the inclusion criteria. The OR rates of bone metastases at 3 months were 45% (95% confidence interval [CI], 31–60%) and 36% (95% CI, 25–49%) in the SBRT and cEBRT arms, respectively. These studies showed no significant difference between the two groups (risk ratio = 1.19; 95% CI, 0.93–1.53; p = 0.14). In the four studies included for the calculation of OR rates of spinal metastases at 3 months, the SBRT and cEBRT arms included 390 and 307 patients, respectively. The OR rates were 40% (95% CI, 21–62%) and 35% (95% CI, 26–44%) in the SBRT and cEBRT arms, respectively. There was no significant difference between the two groups (risk ratio = 1.14; 95% CI, 0.71–1.84; p = 0.44). The incidence of adverse effects and outcomes of health-related quality of life were comparable between the two arms. <h3>Conclusion</h3> The superiority of SBRT for bone metastases and spinal metastases over cEBRT for pain palliation was not confirmed in this meta-analysis. Although SBRT is a standard of care, treatment indications should not be blindly expanded.

Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiotherapy to Conventional Palliative External Beam Radiotherapy

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) improves complete pain response for painful spinal metastases compared to conventional external beam radiotherapy (cEBRT). We report mature local control and reirradiation rates in a large cohort of patients treated with SBRT vs. cEBRT enrolled previously in the Canadian Clinical Trials Group Symptom Control (SC).24 phase II/III trial. <h3>Materials/Methods</h3> 137/229 (60%) patients randomized to 24 Gy in 2 SBRT fractions or 20 Gy in 5 cEBRT fractions were retrospectively reviewed. By including all treated spinal segments, we report on 66 patients (119 spine segments) treated with SBRT, and 71 patients (169 segments) treated with cEBRT. The primary outcomes were MR-based local control and reirradiation rates for each treated spine segment. <h3>Results</h3> The median follow-up was 11.3 months (IQR:5.3-27.7 months), and median OS in the SBRT and cEBRT cohorts were 21.6 and 18.9 months (p=0.428), respectively. The cohorts were balanced with respect to radioresistant histology and presence of "Mass" (paraspinal and/or epidural disease extension). Risk of local failure after SBRT vs. cEBRT at 6, 12 and 24 months were 2.8% vs. 11.2%, 6.1% vs. 28.4% and 14.8% vs. 35.6%, respectively (p<0.001). cEBRT (HR:3.48, 95%CI:1.94-6.25, p<0.001) and presence of "Mass" (HR:2.07, 95%CI:1.29-3.31, p=0.002) independently predicted local failure on multivariable analysis. The 1-year reirradiation rates and median times to reirradiation after SBRT vs. cEBRT, were 2.2% vs 15.8% (p=0.002) and 22.9 months vs. 9.5 months respectively. Radioresistant histology (HR:2.66, 95%CI:1.43-4.94, p=0.002) and cEBRT (HR:2.34, 95%CI:1.14-4.78, p=0.002) independently predicted for reirradiation. 8/12 iatrogenic vertebral compression fractures (VCFs) were after SBRT and 4/12 after cEBRT; Grade 3 toxicities were isolated to the SBRT cohort (5/12). <h3>Conclusion</h3> Risk of local failure and reirradiation is lower with SBRT compared to cEBRT for spinal metastases. Although the iatrogenic VCF rates were within expectations, Grade 3 VCF were isolated to the SBRT cohort.

Evaluating and Optimizing Prognostic Modeling for Patients Undergoing Stereotactic Body Radiotherapy for Bone Metastases

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) holds an expanding role in the treatment of bone metastases. As compared to conventional external beam radiation (cEBRT), SBRT may be best applied to specific subsets of patients with more favorable prognosis and may prolong survival time. This calls into question the generalizability of survival estimates from prognostic models built from more general patient populations treated with cEBRT. We investigate the external validity of three such models for patients treated with bone-directed SBRT and identify approaches to optimize prognostication for this population. <h3>Materials/Methods</h3> Patients treated with SBRT for bone metastases from 1/2017-12/2019 at 3 radiation oncology facilities were identified through retrospective electronic medical record review. Demographic, disease, and treatment data were collected, including the covariates of 3 previously-validated models built in populations that excluded SBRT: the 27-item Bone Metastases Ensemble Trees for Survival (BMETS) machine-learning model and 2 Cox regression models—Chow's 3-item (C-3) and Westhoff's 2-item (W-2) tools. Individualized estimates for risk of death at various time points after consultation were obtained using each model. Time-dependent area under the curve (tAUC), calibration plots, and Brier scores evaluated model discrimination, calibration, and overall performance when each model was applied to the SBRT validation set. <h3>Results</h3> A total of 192 sites in 168 patients were included. Patients were 65.5% male; 74% white, 17% black and 8% other; with median age of 63 years (range: 18-92), and median Karnofsky Performance Status of 90 (range: 50-100). Histologies were prostate (31%), lung (15%), breast (10%), and other (44%). Estimated median overall survival was 3.3 years. BMETS tAUC was 0.73, 0.81, and 0.81 at 6, 9, and 12 months, with significant outperformance (p<0.05) of C-3 and W-2 models by the 12-month time point (tAUC 0.71 and 0.75, respectively). Calibration plots showed overestimation of risk of death in all 3 models. Brier scores for BMETS, C-3 and W-2 were respectively 0.24, 0.28 and 0.25 at 12 months; the simple baseline model from the Kaplan-Meier curve estimate (Brier score 0.19) outperformed all 3 models. Subsequent analyses identified variables absent from the 3 models strongly predictive of survival in the SBRT cohort, including number of metastatic lesions. <h3>Conclusion</h3> When applied to an SBRT cohort, BMETS maintained excellent discrimination at time points >6 months, outperforming C-2 and W-3 models. Yet, each model underestimated specific survival probabilities, suggesting that tools built from non-SBRT populations may be poorly calibrated for SBRT and supporting use of SBRT-specific prognostic tools. To address this, we have modified the BMETS web platform to permit for users to select for SBRT and non-SBRT specific survival predictions.

Dose-Escalated Two-Fraction Spine Stereotactic Body Radiotherapy: 28 Gy vs. 24 Gy in 2 Daily Fractions

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) for spine metastases improves pain response rates and local control compared to conventional external beam radiotherapy, however, the optimal fractionation schedule is unclear. We report local control and toxicity outcomes after dose-escalated two-fraction spine SBRT. <h3>Materials/Methods</h3> A prospectively maintained institutional database of over 600 patients and 1400 vertebral segments treated with spine SBRT, using an established treatment technique, was reviewed to identify those treated with 28 Gy or 24 Gy in two daily fractions. The primary endpoint was MRI-based local failure (LF), and secondary endpoints included overall survival (OS) and vertebral compression fracture (VCF). <h3>Results</h3> A total of 947 treated vertebral segments in 482 patients were identified, of which 159 patients (301 segments, 31.8%) received 28 Gy and 323 patients (646 segments, 68.2%) received 24 Gy in 2 fractions. Median follow-up was 23.5 months and median OS was 49.1 months. In the 28 Gy cohort, the 6-, 12-, and 24-month cumulative incidences of local failure were 3.5%, 5.4% and 11.1%, respectively, vs. 6.0%, 12.5% and 17.6% in the 24 Gy cohort, respectively (p=0.0075). On multivariable analysis, 24 Gy (HR: 1.572, 95%CI: 1.08-2.30, p=0.0196), epidural disease (HR: 1.522, 95%CI: 1.10-2.10, p=0.0108), and paraspinal extension (HR: 1.517, 95%CI: 1.08-2.12, p=0.0151) predicted for greater rates of local failure. Risk of VCF was 5.5%, 7.6% and 10.7% at 6-, 12- and 24-months, respectively, and similar between the two cohorts (p=0.573). Spinal malalignment (p<0.001), baseline vertebral body collapse (p=0.0027), junctional spine location (p=0.0296), and a greater PTVD90 predicted for greater rates of VCF. <h3>Conclusion</h3> 28 Gy in 2 daily fractions was associated with improved local control without increasing the risk of VCF, and the 2-year local control rates fit the HYTEC spine tumor control probability model.

Stereotactic body radiotherapy versus conventional radiotherapy for painful bone metastases: a systematic review and meta-analysis of randomised controlled trials

BackgroundStereotactic body radiotherapy (SBRT) is a promising approach in treating painful bone metastases. However, the superiority of SBRT over conventional external beam radiotherapy (cEBRT) remains controversial. Therefore, this systematic review and meta-analysis of randomised controlled trials was conducted to compare SBRT and cEBRT for the treatment of bone metastases.MethodsA search was conducted using PubMed on January 22, 2022, with the following inclusion criteria: (i) randomised controlled trials comparing SBRT with cEBRT for bone metastases and (ii) endpoint including pain response. Effect sizes across studies were pooled using random-effects models in a meta-analysis of risk ratios.ResultsA total of 1246 articles were screened, with 7 articles comprising 964 patients (522 and 442 patients in the SBRT and cEBRT arms, respectively) meeting the inclusion criteria. The overall pain response (OR) rates of bone metastases at 3 months were 45% and 36% in the SBRT and cEBRT arms, respectively. The present analyses showed no significant difference between the two groups. In four studies included for the calculation of OR rates of spinal metastases at three months, the OR rates were 40% and 35% in the SBRT and cEBRT arms, respectively, with no significant difference between the two groups. The incidence of severe adverse effects and health-related quality of life outcomes were comparable between the two arms.ConclusionsThe superiority of SBRT over cEBRT for pain palliation in bone metastases was not confirmed in this meta-analysis. Although SBRT is a standard of care for bone metastases, patients receiving SBRT should be selected appropriately.

Fifty-year history of the evolution of spinal metastatic disease management.

Spine metastases are a significant source of morbidity in oncology. Treatment of these spine metastases largely remains palliative, but advances over the past 50 years have improved the effectiveness of interventions for preserving functional status and obtaining local control while minimizing morbidity. While the field began with conventional external beam radiation as the primary treatment modality, a series of paradigm shifts and technological advances in the 2000s led to a change in treatment patterns. These advances allowed for an increased role of surgical decompression of neural elements, a shift in the stereotactic capabilities of radiation oncologists, and an improved understanding of the radiobiology of metastatic disease. The result was improved local control while minimizing treatment morbidity. These advances fit within the larger framework of metastatic spine tumor management known as the Neurologic, Oncologic, Mechanical, and Systemicdisease decision framework. This dynamic framework takes into account the neurological function of the patient, the radiobiology of their tumor, their degree of mechanical instability, and their systemic disease control and treatment options to help determine appropriate interventions based on the individual patient. Herein, we describe the 50-year evolution of metastatic spine tumor management and the impact of various advances onthe field.

Stereotactic Gamma Knife® Radiosurgery of Intraocular Retinoblastoma: Six-Year Experience.

BackgroundExternal beam radiotherapy for resistant retinoblastoma is now seen as a last resort to saving the eye because of the risk of severe side effects: secondary cancers and cosmetic problems of orbital bone growth retardation. To reduce such complications, treatment modalities have shifted towards new radiation therapy techniques. No information on single fraction Gamma Knife® radiosurgery (GKRS) for intraocular retinoblastoma exists.Materials and methodsEighteen children (19 eyes) with retinoblastoma were treated with GKRS. The mean age at the time of treatment was 35 months (from 12 to 114 months). Before GKRS, all routes of chemotherapy delivery were held in all cases. The eligibility criteria for GKRS were retinoblastomas not amenable either to systemic or local chemotherapy and local ophthalmological treatment, retinoblastomas too large for conventional local methods, and inability to perform intraarterial chemotherapy. Conventional external beam radiotherapy was excluded in the presented cases, given the possible complications mentioned above. In every case, eye removal was suggested to the child's parents, but they flatly refused. GKRS was proposed as the last chance to save the eye (in four cases, it was performed on the only eye). The median prescribed dose was 22 Gy (interquartile range [IQR]: 18-35 Gy), and the median prescribed isodose was 50% (IQR: 36-90%).ResultsLocal control was achieved in 79% of cases (complete tumor regression in 69%, incomplete regression in 10%). Two eyes (10.5%) could not be preserved and had to be enucleated due to the tumor recurrence. Two eyes (10.5%) developed secondary complications (total vitreous hemorrhage, retinal detachment, and iris neovascularization), making adequate tumor control nearly impossible. Overall, 15 eyes (79%) were preserved, and four eyes (21%) were enucleated after GKRS with no signs of tumor recurrence and metastasis in the mean follow-up of 41 months. No acute radiation side effects occurred in any patient after GKRS. Ten children (10 eyes, 53%) were diagnosed with vitreous hemorrhage from mild to severe. Three eyes presented with optic neuropathy one year after GKRS, and four eyes developed retinopathy. Radiation-induced cataract occurred in two eyes. There were no cases of secondary glaucoma or keratopathy in our study. All patients and eyes treated by GKRS were stable within 41 months (from seven to 74 months).ConclusionsSingle fraction Gamma Knife® radiosurgery may be a reasonable salvage treatment for resistant and recurrent retinoblastoma as an alternative approach to enucleation in selected cases. GKRS should be considered in retinoblastoma management.

47: Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiotherapy to Conventional Palliative External Beam Radiotherapy

47: Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiotherapy to Conventional Palliative External Beam Radiotherapy

Advances in the management of spinal metastases: what the radiologist needs to know.

Spine is the most frequently involved site of osseous metastases. With improved disease-specific survival in patients with Stage IV cancer, durability of local disease control has become an important goal for treatment of spinal metastases. Herein, we review the multidisciplinary management of spine metastases, including conventional external beam radiation therapy, spine stereotactic radiosurgery, and minimally invasive and open surgical treatment options. We also present a simplified framework for management of spinal metastases used at The University of Texas MD Anderson Cancer Center, focusing on the important decision points where the radiologist can contribute.

Palliative Efficacy of High-Dose Stereotactic Body Radiotherapy Versus Conventional Radiotherapy for Painful Non-Spine Bone Metastases: A Propensity Score-Matched Analysis.

Simple SummaryAs the superiority of stereotactic body radiotherapy (SBRT) over conventional external beam radiotherapy (cEBRT) for painful non-spine bone metastases remains controversial, we conducted propensity score-matched analysis. Our results showed that the 3-month pain response rate after SBRT was significantly higher than that after cEBRT. Therefore, these findings suggest that large-scale randomized controlled trials are warranted to compare SBRT with cEBRT for painful bone metastases not involving the spine.(1) Background: The superiority of stereotactic body radiotherapy (SBRT) over conventional external beam radiotherapy (cEBRT) in terms of pain palliation for bone metastases remains controversial. (2) Methods: This propensity score-matched study compared the overall pain response (OR) 3 months after radiotherapy among patients with painful (≥2 points on a 0-to-10 scale) non-spine bone metastases. Patients with lesions that were treated with SBRT or cEBRT and whose pain scores were evaluated 3 months after radiotherapy were included in this study. Pain response was evaluated according to the International Consensus Criteria. (3) Results: A total of 234 lesions (SBRT, n = 129; cEBRT, n = 105) were identified in our institutional database. To reduce the confounding effects, 162 patients were selected using a propensity score-matched analysis (n = 81 for each treatment). The OR rate at 3 months after SBRT was significantly higher than that after cEBRT (76.5% vs. 56.8%; p = 0.012). A noteworthy finding of our study is that the same trend was observed even after 6 months (75.9% vs. 50.0%; p = 0.011). The 1-year local failure rates after SBRT and cEBRT were 10.2% and 33.3% (p < 0.001), respectively. (4) Conclusions: Our findings suggest that SBRT is superior to cEBRT for pain palliation in patients with non-spine bone metastases.

P121. Carbon fiber reinforced PEEK implants for spine tumors: a single center experience

<h3>BACKGROUND CONTEXT</h3> Titanium is the most common material used to manufacture spinal implants; however, its metallic properties are associated with imaging artifacts on CT and MRI scans which impede treatment planning and clinical follow among oncologic patients. Carbon fiber-reinforced Polyether ether ketone (CFR-PEEK) based spinal implants are an alternative to titanium, offering less image artifact as its titanium counterparts while maintaining similar biomechanical and biocompatibility properties. Its use in the management of spinal tumors has been reported, however the perceived advantages related to improved imaging quality, radiation treatment planning, and detection of tumor recurrence have not been fully assessed. <h3>PURPOSE</h3> We report our experience at the MD Anderson Cancer Center with the use of CFR-PEEK implants in the treatment of oncological patients. <h3>STUDY DESIGN/SETTING</h3> Retrospective single-arm single-center study. <h3>PATIENT SAMPLE</h3> All consecutive patients from September 2019 to July 2021 who were operated for spine conditions and had carbon fiber-reinforced implants. <h3>METHODS</h3> We performed a retrospective review of the medical records and imaging studies of patients treated with CFR-PEEK implants from September 2019 to July 2021. Histology type, tumor location, construct features, time of follow up, type of adjuvant radiation, recurrences, overall survival and hardware related complications were recorded. <h3>RESULTS</h3> Seventy-one consecutive patients were assessed (20 primary tumors, 47 metastases, 4 others). The median time for followup was 5.4 months (Q1 1.13, Q3 11.9, IQR 10.77). Of those 6 patients received conventional external beam radiotherapy, 31 received spinal stereotactic radiosurgery with a median time to radiation of 35 days among primary tumors and 30 days among metastatic cases. A total of 4 patients with primary tumors presented recurrence at a median time of 4.7 months (N=4, Q1 2.7, Q3 7, IQR 4.3) and 7 patients with metastatic disease presented recurrence at a median time of 3.4 months (N=6, Q1 2.0, Q3 5.1, IQR 3.1). Hardware complications were observed in a total of 5 cases (7.04%) and included screw loosening, intraoperative screw breakage and loosened set screw. Imaging review demonstrated significant reduction in imaging artifact and enhanced detection of local recurrence when compared to similar cases operated with standard titanium spinal instrumentation. <h3>CONCLUSIONS</h3> Carbon fiber reinforced PEEK implants provided safe and effective spinal stabilization for patients with both primary and metastatic tumors while integrating into postoperative imaging and radiation planning. The associated reduction in imaging artifacts enhanced postoperative radiation planning and the ability to detect local recurrence. <h3>FDA DEVICE/DRUG STATUS</h3> Carbon fiber thoracolumbar screws and rods (Icotec AG, Altstätten, Switzerland) (Approved for this indication)

SPIN-01 RADIATION THERAPY ALONE VERSUS RADIATION THERAPY PLUS RADIOFREQUENCY ABLATION/VERTEBRAL AUGMENTATION FOR SPINE METASTASIS: TRIAL IN PROGRESS

BACKGROUNDSpine metastases are a common occurrence in cancer patients and result in pain, neurologic deficits, decline in performance status, disability, inferior quality of life (QOL), and reduction in ability to receive cancer-directed therapies. Conventional external beam radiation therapy (EBRT) is associated with modest rates of pain relief, high rates of disease recurrence, low response rates for those with radioresistant histologies, and limited improvement in neurologic deficits. The addition of radiofrequency ablation/percutaneous vertebral augmentation (RFA/PVA) to index sites together with EBRT may improve pain response rates and corresponding quality of life. METHODS/DESIGNThis is a single-center, prospective, randomized, controlled trial in patients with spine metastases from T5-L5, stratified according to tumor type (radioresistant vs. radiosensitive) in which patients in each stratum are randomized in a 2:1 ratio to either RFA/PVA and EBRT or EBRT alone. All patients are treated with EBRT to a dose of 20-30 Gy in 5-10 fractions. The target parameters are measured and recorded at the baseline clinic visit, and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments. DISCUSSIONThe primary objective of this randomized trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to palliative EBRT alone for patients with spine metastases, defined as complete or partial pain relief (measured using the Numerical Rating Pain Scale [NRPS]) at 3 months. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall QOL. The results from this study will be used to allow for comparisons to alternative treatment approaches. This trial was activated 5/2020 and is open to accrual.

Radiotherapy for bone metastases of hepatocellular carcinoma: a hybrid systematic review with meta-analyses

Introduction External beam radiation therapy (EBRT) is commonly used as a palliative treatment for bone metastases of hepatocellular carcinoma (HCC). We planned a hybrid systematic review that meta-analyzed the efficacy and feasibility of EBRT and reviewed the literature to answer specific clinical questions. Methods The PubMed, Medline, Embase, and Cochrane Library databases were searched through 1 December 2021. Primary endpoints were overall survival (OS) and response rate (RR). Secondary endpoints were comparative data, including treatment response and survival related to dose escalation, number of metastases, and fractionation scheme. Formal pooled analyses were performed on the primary endpoints, and the secondary endpoints were systematically reviewed. Complications were also reviewed. Results Nineteen studies involving 1613 patients with HCC and bone metastases were included. The median OS was 6 months (range: 3–13 months). The pooled one-year OS was 23.1% (95% confidence interval [CI]: 18.4–28.6); pooled pain RR was 81.5% (95% CI: 76.4–85.7) and of pain complete remission was 26.5% (95% CI: 21.7–32.0). Pain response might be related to dose escalation, considering the moderate consistency of results and plausibility, with a low-quality grade of evidence†. Considering the indeterminate results, we cannot suggest that dose escalation is correlated with OS. The oligometastasis status might be related to better OS, considering the high consistency of results and plausibility with low to moderate quality of evidence. Hypofractionated EBRT might yield comparable efficacy to conventional EBRT, with a low-quality grade of evidence. There were few complications of grade ≥3, except for hematologic complications, which ranged from 11.5to 34%. Conclusion EBRT is an efficient and feasible palliative option. Clinical consideration of hematologic complications is necessary. Future studies are needed to increase the quality of evidence for actual clinical questions. †Reference to a system of the American Society for Radiation Oncology primary liver cancer clinical guidelines.

Holistic Approach to the Diagnosis and Treatment of Patients with Tumor Metastases to the Spine.

Simple SummarySpine metastases constitute a significant social problem. The spine is a frequent site of metastases of various neoplasms. Our goal was to draw attention to the complexity of that problem and the diagnostic possibilities, qualification nuances, and application of the appropriate treatment method. We focused on the holistic approach to patient care. This review comprehensively covers the current knowledge in the field.The treatment of neoplastic spine metastases requires multi-faceted assessment and an interdisciplinary approach to patients. The metastases do not show specific symptoms but are often the first confirmation of the presence of a primary tumor in a patient. The diagnostic process includes imaging and invasive procedures, e.g., biopsy. It is essential to qualify the patient for an appropriate treatment using dedicated scales. Decompression of the spinal cord is a critical issue to save or restore neurological function in a patient with spine metastases. Surgical treatment ought to meet three criteria: release spinal cord and nerve roots, restore the spine’s anatomical relations, and ensure the internal stabilization of the spine. A good result from surgical treatment enables the continuation of radiotherapy, chemotherapy, hormone therapy, and targeted molecular therapy. Stereotactic radiosurgery and stereotactic body radiotherapy are more effective ways of treating spine metastases than conventional external beam radiotherapy. They allow higher doses of radiation, concentrated precisely at the tumor site. Our review summarizes the established and emerging concepts in the treatment of spine metastases. A holistic approach to the patient enables the selection of the appropriate therapy.

Glioblastoma - treatment and obstacles.

BackgroundGlioblastoma is the most common and aggressive primary tumor in adults. A narrative review of all the relevant papers known was conducted.Materials and methodsReviews, clinical trials, and randomized controlled trials published from 1981 through September 2021 and written, or at least abstracted, in English were analyzed.ResultsThe standard of care for glioblastoma is the maximum safe resection possible, followed by radiation therapy and concurrent temozolomide (TMZ) and daily TMZ and tumor treatment fields (TTFields) after irradiation. There is no evidence to date of the benefit of brachytherapy, radiosurgery (SRS), fractional stereotactic radiotherapy (FSRT), and hyperfractionated radiotherapy over conventional external beam radiation therapy (EBRT) for the primary tumor. The assessment of age and performance status before treatment in the elderly enables hypofractionated radiotherapy. The research of tumor molecular signatures contributes to the choice of the best-targeted drug therapy. In recurrent glioblastoma, it is necessary to balance the risks and benefits of re-radiation and association with bevacizumab. Solid data confirming the role of immunotherapy in the treatment of malignant glioma are still lacking.ConclusionsAlthough the treatment of glioblastoma has evolved in terms of local control, mortality remains close to 12 months after diagnosis. To obtain better results and reduce recurrence, future research needs to investigate the frontiers of knowledge, such as the elucidation of the molecular mechanisms related to the tumor, the optimization of drugs to overcome the blood-brain barrier effectively, and the discovery of new therapies aimed at the heterogeneous profile of this neoplasm.

Decision Making in the Management of Metastatic Spinal Tumors

The advent of newer systemic therapies has resulted in improved survival of cancer patients. Increased life expectancy necessitates strategies not only for palliation to improve quality of life but also for lasting local control of the spinal metastasis. In patients with a short life expectancy, palliative surgery involves decompression of neural structures by debulking the tumor and spine stabilization followed by conventional external beam radiotherapy (cEBRT). Ablative surgery involves more aggressive tumor resection followed by cEBRT. The introduction of stereotactic body radiotherapy (SBRT) has challenged traditional paradigms for decision-making further. With SBRT, hitherto radioresistant tumors can also be successfully treated with radiotherapy alone, in selected cases without spinal instability or severe epidural spinal cord compression. Minimally invasive surgical techniques such as percutaneous cement augmentation, percutaneous stabilization, and minimally invasive decompression and tumor resection have further reduced the surgical morbidity, enabling extension of treatment to more sick patients. The eventual decision regarding the treatment strategy is made on a case-by-case basis by a multidisciplinary team along with the patient and his/her family.

Radiation myelopathy following stereotactic body radiation therapy for spine metastases.

Stereotactic body radiation therapy (SBRT) is now considered a standard of care treatment option in the management of spine metastases. One of the most feared complications of spine SBRT is radiation myelopathy (RM). We provided a narrative review of RM following spine SBRT based on review of the published literature, including data on spinal cord dose constraints associated with the risk of RM, strategies to mitigate the risk, and management options for RM. There are limited published data of cases of RM following spine SBRT with detailed spinal cord dosimetry. The HyTEC report provided recommendations for the point maximal dose (Dmax) for the spinal cord that is associated with a < 5% risk of RM for 1-5 fractions spine SBRT. In the setting of spine SBRT reirradiation after previous conventional external beam radiation therapy (cEBRT), factors associated with RM are: SBRT spinal cord Dmax, cumulative spinal cord Dmax, and the time interval between previous RT and SBRT reirradiation. There are various strategies to mitigate the risk of RM, including accurate delineation of the spinal cord (or thecal sac), strict adherence to the recommended spinal cord dose constraints, and robust treatment immobilisation set-up and delivery. Limited effective treatment options are available for patients who develop RM, and these include corticosteroids, hyperbaric oxygen, and bevacizumab; however, none have been supported by high quality evidence. RM is a rare but devastating complication following SBRT for spine metastases. There are strategies to minimise the risk of RM to ensure safe delivery of spine SBRT.

Treatment of Metastatic Spinal Disease; what the Radiologist needs to know.

Advancements in technology and multidisciplinary management have revolutionized the treatment of spinal metastases. Imaging plays a pivotal role in determining the treatment course for spinal metastases. This article aims to review the relevant imaging findings in spinal metastases from the perspective of the treating clinician, describe the various treatment options, and discuss factors influencing choice for each available treatment option. Cases that once required radical surgical resection or low-dose conventional external beam radiation therapy, or both, are now being managed with separation surgery, spine stereotactic radiosurgery/stereotactic body radiation therapy, or both, with decreased morbidity, improved local control, and more durable pain control. The primary focus in determining treatment choice is now on tumor control outcomes, treatment-related morbidity, and quality of life.