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Purpose: A PENTEC (Pediatric Normal Tissue Effects in the Clinic) review was performed to estimate the dose-volume effects of radiation therapy on spine deformities and growth impairment for patients who underwent radiation therapy as children., Methods and Materials: A systematic literature search was performed to identify published data for spine deformities and growth stunting. Data were extracted from 12 reports of children irradiated to the spine (N = 603 patients). The extracted data were analyzed to find associations between complication risks and the radiation dose (conventional fractionation throughout) as impacted by exposed volumes and age using the mixed-effects logistic regression model. When appropriate, corrections were made for radiation modality, namely orthovoltage beams., Results: In the regression analysis, the association between vertebral dose and scoliosis rate was highly significant (P < .001). Additionally, young age at time of radiation was highly predictive of adverse outcomes. Clinically significant scoliosis can occur with doses ≥15 Gy to vertebrae during infancy (<2 years of age). For children irradiated at 2 to 6 years of age, overall scoliosis rates of any grade were >30% with doses >20 Gy; grade 2 or higher scoliosis was correlated with doses ≥30 Gy. Children >6 years of age remain at risk for scoliosis with doses >30 Gy; however, most cases will be mild. There are limited data regarding the effect of dose gradients across the spine on degree of scoliosis. The risk of clinically meaningful height loss was minimal when irradiating small volumes of the spine up to 20 Gy (eg, flank irradiation), except in infants who are more vulnerable to lower doses. Growth stunting was more frequent when larger segments of the spine (eg, the entire spine or craniospinal irradiation) were irradiated before puberty to doses >20 Gy. The effect was modest when patients were irradiated after puberty to doses >20 Gy., Conclusions: To reduce the risk of kyphoscoliosis and growth impairment, the dose to the spine should be kept to <20 Gy for children <6 years of age and to <10 to 15 Gy in infants. The number of vertebral bodies irradiated and dose gradients across the spine should also be limited when possible., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Vertebral Stereotactic ablative body radiotherapy (SABR) involves substantial tumour density heterogeneities. We evaluated the impact of a linear Boltzmann transport equation (LBTE) solver dose calculation on vertebral SABR dose distributions. A sequential cohort of 20 patients with vertebral metastases treated with SABR were selected. Treatment plans were initially planned with a convolution style dose calculation algorithm. The plan was copied and recalculated with a LBTE algorithm reporting both dose to water (D w ) or dose to medium (D m ). Target dose as a function of CT number, and spinal cord dose was compared between algorithms. Compared with a convolution algorithm, there was minimal change in PTV D90% with LBTE. LBTE reporting D m resulted in reduced GTV D50% by (mean, 95% CI) 2.2% (1.9-2.6%) and reduced Spinal Cord PRV near-maximum dose by 3.0% (2.0-4.1%). LBTE reporting D w resulted in increased GTV D50% by 2.4% (1.8-3.0%). GTV D50% decreased or increased with increasing CT number with D m or D w respectively. LBTE, reporting either D m or D w resulted in decreased central spinal cord dose by 8.7% (7.1-10.2%) and 7.2% (5.7-8.8%) respectively. Reported vertebral SABR tumour dose when calculating with an LBTE algorithm depends on tumour density. Spinal cord near-maximum dose was lower when using LBTE algorithm reporting D m , which may result in higher spinal cord doses being delivered than with a convolution style algorithm. Spinal cord central dose was significantly lower with LBTE, potentially reflecting LBTE transport approximations., (© 2021. Australasian College of Physical Scientists and Engineers in Medicine.)

Aim: To explore the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for evaluating early outcomes of CyberKnife radiosurgery for spinal metastases., Materials and Methods: Patients with spinal metastases who were treated with CyberKnife radiosurgery from July 2018 to December 2020 were enrolled. Conventional MRI and DCE-MRI were performed before treatment and at 3 months after treatment. Patients showing disease progression were defined as the progressive disease (PD) group and those showing complete response, partial response, and stable disease were defined as the non-PD group. The haemodynamic parameters (volume transfer constant [Ktrans], rate constant [Kep], and extravascular space [Ve]) before and after treatment between the groups were analysed. Area under the curve (AUC) values were calculated., Results: A total of 27 patients with 39 independent spinal lesions were included. The median follow-up time was 18.6 months (6.2-36.4 months). There were 27 lesions in the non-PD group and 12 lesions in the PD group. Post-treatment Kep, ΔKtrans and ΔKep in the non-PD group (0.959/min, - 32.6% and -41.1%, respectively) were significantly lower than the corresponding values in PD group (1.429/min, 20.4% and -6%; p<0.05). Post-treatment Ve and ΔVe (0.223 and 27.8%, respectively) in the non-PD group were significantly higher than that of the PD group (0.165 and -13.5%, p<0.05). ΔKtrans showed the highest diagnostic efficiency, with an AUC of 0.821., Conclusions: DCE-MRI parameters change significantly at an early stage after CyberKnife stereotactic radiosurgery for spinal metastases. DCE-MRI may be of value in determining the early treatment response., (Copyright © 2021. Published by Elsevier Ltd.)

The authors present a case of delayed radiation myelopathy in a 12-year-old girl with Hodgkin lymphoma and Artemis mutation. This is the first of such a case presented in the literature., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We aimed to clarify the outcomes of re-irradiation stereotactic body radiotherapy for spinal metastases with a uniform dose fractionation schedule at our institution., Methods: Data of patients treated with re-irradiation stereotactic body radiotherapy for spinal metastases (September 2013-March 2020) were retrospectively reviewed. The prescribed dose was 24 Gy in two fractions. The spinal cord dose constraint and dose for previously irradiated cases ≥50 Gy in 25 fractions were 12.2 Gy (maximum dose) and 11 Gy, respectively. The endpoints were pain control, local failure and adverse effects. Pain status was measured on a scale of 0-10 using the patients' self-reports and pain response was defined using international consensus criteria. Local failure was defined as tumor progression on imaging evaluations., Results: We assessed 133 lesions in 123 patients, where 70 (52.6%) had three or more spinal levels treated, 58 (43.6%) had previous irradiation doses of 40 Gy or more and 53 (39.8%) had the targets compressing the cord. The median follow-up was 12 months and the 3-, 6- and 12-month pain response rate was 75, 64 and 59%, respectively. The 1-year local failure rate was 25.8%. Previous irradiation dose was not correlated with local failure rate (P = 0.13). Radiation-induced myelopathy, radiculopathy and vertebral compression fractures were observed in 4 (3.0%), 2 (1.5%) and 17 (13.8%) lesions, respectively. A trend towards an association between any toxicity and previous irradiation dose was not observed., Conclusions: Re-irradiation spine stereotactic body radiotherapy achieved good local control and pain control, with reduced risk of radiation myelopathy., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The phenomenon of a massive vertebral deformity was recorded in the radiating Labeobarbus assemblage from the middle reaches of the Genale River (south-eastern Ethiopia, East Africa). Within this sympatric assemblage, five trophic morphs-generalized, lipped, piscivorous and two scraping feeders-were reported between 1993 and 2019. In 2009, a new morph with prevalence of ~10% was discovered. The new morph, termed 'short', had an abnormally shortened vertebral column and a significantly deeper body. This type of deformity is common in farmed Atlantic salmon and other artificially reared fish, but is rare in nature. In the Genale Labeobarbus assemblage, the deformity was present exclusively within the generalized and lipped morphs. The short morph had between seven and 36 deformed (compressed and/or fused) vertebrae. Their body depth was positively correlated with number of deformed vertebrae. In another collection in 2019, the short morph was still present at a frequency of 11%. Various environmental and genetic factors could contribute to the development of this deformity in the Genale Labeobarbus, but based on the available data, it is impossible to confidently identify the key factor(s). Whether the result of genetics, the environment, or both, this deep-bodied phenotype is assumed to be an anti-predator adaptation, as there is evidence of its selective advantage in the generalized morph. The Genale monstrosity is the first reported case of a massive deformity of the vertebral column in a natural population of African fishes., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Fractures are known to shorten life expectancy and worsen the quality of life. The risk of fractures after radiation therapy in cervical cancer patients is known to be multifactorial. In this study, we examined risk factors for fractures in cervical cancer patients, especially by evaluating bone densities and DVH parameters for fractured bones., Materials and Methods: For 42 patients, clinical characteristics, pretreatment CT bone densities, and radiation dose were compared between patients with and without fractures., Results: Posttreatment fractures occurred in 25 bones among ten patients. Pretreatment CT bone densities were significantly lower in patients with fractures (P < 0.05-0.01 across sites, except for the ilium and the ischium). Although DVH parameters were also significantly associated with fractures in univariate analysis, only CT densities were significantly associated with fractures in multivariate analysis., Conclusion: Pretreatment CT densities of spinal and pelvic bones, which may reflect osteoporosis, have a significant impact on the risk for posttreatment fractures.

Purpose: To monitor intrafraction motion during spine stereotactic body radiotherapy(SBRT) treatment delivery with readily available technology, we implemented triggered kV imaging using the on-board imager(OBI) of a modern medical linear accelerator with an advanced imaging package. Methods: Triggered kV imaging for intrafraction motion management was tested with an anthropomorphic phantom and simulated spine SBRT treatments to the thoracic and lumbar spine. The vertebral bodies and spinous processes were contoured as the image guided radiotherapy(IGRT) structures specific to this technique. Upon each triggered kV image acquisition, 2D projections of the IGRT structures were automatically calculated and updated at arbitrary angles for display on the kV images. Various shifts/rotations were introduced in x, y, z, pitch, and yaw. Gantry-angle-based triggering was set to acquire kV images every 45°. A group of physicists/physicians(n = 10) participated in a survey to evaluate clinical efficiency and accuracy of clinical decisions on images containing various phantom shifts. This method was implemented clinically for treatment of 42 patients(94 fractions) with 15 second time-based triggering. Result: Phantom images revealed that IGRT structure accuracy and therefore utility of projected contours during triggered imaging improved with smaller CT slice thickness. Contouring vertebra superior and inferior to the treatment site was necessary to detect clinically relevant phantom rotation. From the survey, detectability was proportional to the shift size in all shift directions and inversely related to the CT slice thickness. Clinical implementation helped evaluate robustness of patient immobilization. Based on visual inspection of projected IGRT contours on planar kV images, appreciable intrafraction motion was detected in eleven fractions(11.7%). Discussion: Feasibility of triggered imaging for spine SBRT intrafraction motion management has been demonstrated in phantom experiments and implementation for patient treatments. This technique allows efficient, non-invasive monitoring of patient position using the OBI and patient anatomy as a direct visual guide.

Several studies have investigated the effects of the electromagnetic field (EMF) on the central nervous system. However, we encountered no studies of the effects of EMF applied in the prenatal period on the offspring vertebrae. The aim of this study is to investigate the effect of a 900 megahertz (MHz) EMF applied to rat dams in the prenatal period on the vertebrae of rat pups. Female Sprague Dawley rats weighing 180-250 g were used in the experiment. Rats identified as pregnant were divided into two groups, control (n = 3) and EMF (n = 3). No EMF was applied to the control group pregnant rats. EMF was applied to the EMF group rats for 1 h daily on an equal and standard basis on prenatal days 13-21. All newborn rat pups were divided into pup control (n = 6) (PC) and pup EMF (n = 6) (PEMF) groups, and no treatment was performed on either. All animals were decapitated on day 32, and the spinal cord in the upper thoracic region was harvested. Vertebral tissues were subjected to routine histological procedures. Histopathological examination revealed that PEMF group vertebral cartilage had been converted into bone tissue. Comparison of central canal diameter and area values between the PEMF group and the PC group revealed statistically significant increases in the PEMF group (p = 0.000 and p = 0.001, respectively). Statistical analysıs revealed no significant difference in mean body weights between the two groups (p > 0.530). Based on these findings, we think that 900 MHz EMF applied in the prenatal period affects the development of the vertebrae. This effect causes pathological changes in the rat pup vertebrae. These findings now raise the question of whether EMF also has an impact on neurological and neurosurgical diseases involving the vertebrae., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: To evaluate long-term degenerative changes in bone and soft tissue after craniospinal irradiation (CSI)., Procedure: An analysis was performed for 892 vertebral bodies in 220 pediatric patients treated with CSI. To analyze vertebral growth, vertebral body height was calculated. Signal changes for vertebral bodies on MRI, scoliosis and kyphosis, degenerative changes of vertebral bones and discs, and wedging or vertebral height loss were analyzed on images, and factors that influenced these changes were investigated., Results: Vertebral growth was significantly correlated with radiation dose and growth hormone (GH) deficiency. Growth rate was significantly worse at a dose >39 Gy. Fatty marrow change was found in 83% of patients, 31% had disc degenerative changes, 13% had degenerative changes of spinal bones, 17% had wedging or spinal height loss, and 27% had scoliosis., Conclusions: Vertebral bone growth was significantly reduced when high doses were administered, and adequate GH replacement was important for bone growth. Even with symmetrical irradiation, the risk of scoliosis is high after CSI. There was also frequent progression of spinal demineralization and degenerative changes after CSI. Therefore, careful attention should be paid to spinal symptoms as pediatric patients grow into adulthood., (© 2020 Wiley Periodicals LLC.)

This study was aimed at assessing the feasibility and toxicity of using stereotactic body radiation therapy (SBRT) for reirradiation of spinal metastatic tumors. We conducted a retrospective review, from our institutional database, of the data of patients who received reirradiation, with overlap of some prescribed isodose lines to the vertebra from the initial radiation therapy, between 2007 and 2019. We identified 40 patients with spinal metastatic tumors, of whom 2 had 2 metastatic vertebral lesions each, totaling up to 42 target lesions. The median dose to spinal cord at the initial radiation therapy was 30 Gy. SBRT based on the intensity-modulated radiation therapy (IMRT) technique was used for reirradiation to spare the spinal cord. All patients received a prescription dose of 25 Gy in 5 fractions to the planning target volume (PTV). Among the 40 cases who had pain, pain relief was obtained in 24 (60%) after reirradiation. Neurologic improvement was obtained in 8 of 15 cases (53%). The adverse events were evaluated using the Common Terminology Criteria for Adverse Events Version 5.0. Reirradiation was well-tolerated, with only 2 patients experiencing adverse events ≥grade 2 in severity, including 1 patient with grade 3 pain, and another patient with grade 3 spinal fracture. None of the patients developed radiation myelopathy. Our data demonstrated that reirradiation of spinal metastasis using SBRT provided effective pain relief and neurologic improvement, with minimal toxicity., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objectives: Cancer survivors with GH deficiency (GHD) receive GH therapy (GHT) after 1+ year observation to ensure stable tumor status/resolution., Hypothesis: Radiation therapy (RT) to brain, spine, or extremities alters growth response to GHT., Aim: Identify differences in growth response to GHT according to type/location of RT., Methods: The Pfizer International Growth Database was searched for cancer survivors on GHT for ≥5 years. Patient data, grouped by tumor type, were analyzed for therapy (surgery, chemotherapy, RT of the focal central nervous system, cranial, craniospinal, or total body irradiation [TBI] as part of bone marrow transplantation), sex, peak stimulated GH, age at GHT start, and duration from RT to GHT start. Kruskal-Wallis test and quantile regression modeling were performed., Results: Of 1149 GHD survivors on GHT for ≥5 years (male 733; median age 8.4 years; GH peak 2.8 ng/mL), 431 had craniopharyngioma (251, cranial RT), 224 medulloblastoma (craniospinal RT), 134 leukemia (72 TBI), and 360 other tumors. Median age differed by tumor group (P < 0.001). Five-year delta height SD score (SDS) (5-year ∆HtSDS; median [10th-90th percentile]) was greatest for craniopharyngioma, 1.6 (0.3-3.0); for medulloblastoma, 5-year ∆HtSDS 0.9 (0.0-1.9); for leukemia 5-year ∆HtSDS, after TBI (0.3, 0-0.7) versus without RT (0.5, 0-0.9), direct comparison P < 0.001. Adverse events included 40 treatment-related, but none unexpected., Conclusions: TBI for leukemia had significant impact on growth response to GHT. Medulloblastoma survivors had intermediate GHT response, whereas craniopharyngioma cranial RT did not alter GHT response. Both craniospinal and epiphyseal irradiation negatively affect growth response to GH therapy compared with only cranial RT or no RT., (© Endocrine Society 2020.)

Background: Craniospinal irradiation (CSI) of childhood tumors with the RapidArc technique is a new method of treatment. Our objective was to compare the acute hematological toxicity pattern during 3D conformal radiotherapy with the application of the novel technique., Methods: Data from patients treated between 2007 and 2014 were collected, and seven patients were identified in both treatment groups. After establishing a general linear model, acute blood toxicity results were obtained using SPSS software. Furthermore, the exposure dose of the organs at risk was compared. Patients were followed for a minimum of 5 years, and progression-free survival and overall survival data were assessed., Results: After assessment of the laboratory parameters in the two groups, it may be concluded that no significant differences were detected in terms of the mean dose exposures of the normal tissues or the acute hematological side effects during the IMRT/ARC and 3D conformal treatments. Laboratory parameters decreased significantly compared to the baseline values during the treatment weeks. Nevertheless, no significant differences were detected between the two groups. No remarkable differences were confirmed between the two groups regarding the five-year progression-free survival or overall survival, and no signs of serious organ toxicity due to irradiation were observed during the follow-up period in either of the groups., Conclusion: The RapidArc technique can be used safely even in the treatment of childhood tumors, as the extent of the exposure dose in normal tissues and the amount of acute hematological side effects are not higher with this technique.

Stereotactic Body Radiation Therapy (SBRT), alternatively termed Stereotactic ABlative Radiotherapy (SABR) or Stereotactic RadioSurgery (SRS), delivers high dose with a sub-millimeter accuracy. It requires meticulous precautions on positioning, as sharp dose gradients near critical neighboring structures (e.g. the spinal cord for spinal tumor treatment) are an important clinical objective to avoid complications such as radiation myelopathy, compression fractures, or radiculopathy. To allow for dose escalation within the target without compromising the dose to critical structures, proper immobilization needs to be combined with (internal) motion monitoring. Metallic fiducials, as applied in prostate, liver or pancreas treatments, are not suitable in clinical practice for spine SBRT. However, the latest advances in Deep Learning (DL) allow for fast localization of the vertebrae as landmarks. Acquiring projection images during treatment delivery allows for instant 2D position verification as well as sequential (delayed) 3D position verification when incorporated in a Digital TomoSynthesis (DTS) or Cone Beam Computed Tomography (CBCT). Upgrading to an instant 3D position verification system could be envisioned with a stereoscopic kilovoltage (kV) imaging setup. This paper describes a fast DL landmark detection model for vertebra (trained in-house) and evaluates its accuracy to detect 2D motion of the vertebrae with the help of projection images acquired during treatment. The introduced motion consists of both translational and rotational variations, which are detected by the DL model with a sub-millimeter accuracy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Bone-modifying agents (BMAs) are frequently used for the treatment of bone metastases. Both BMA and radiation therapy (RT) are effective; however, there are few studies that have evaluated the efficacy of the combination treatment. We evaluated the effectiveness of RT + BMA in breast cancer-induced osteolytic bone metastasis as compared to BMA alone. A total of 43 lesions in 25 patients were evaluated. The median follow-up period was 18 (range, 2-90) months. None of the lesions was treated with chemotherapy or molecular targeted drugs during the follow-up period for evaluating the local response. Patients with complete or partial response were considered as responders, while those with stable or progressive disease were considered as non-responders. The rate of response with RT + BMA was significantly higher than that with BMA alone (P = 0.001). The cumulative incidence rate of response at 6 months was 54.4% in the RT + BMA group and 27.5% in the BMA alone group. The median time to response was 4 (range, 2-11) months in the RT + BMA group and 6 (range, 4-16) months in the BMA alone group. The overall survival rate in the responder group (83.1% at 1 year) was significantly higher than that in the non-responder group (37.5% at 1 year) (P = 0.029). In conclusion, RT combined with BMA was found to be more effective than BMA alone for the treatment of osteolytic bone metastasis, which thereby improves the prognosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Cranio-spinal irradiation (CSI) using protons has dosimetric advantages compared to photons and is expected to reduce risk of adverse effects. The proton relative biological effectiveness (RBE) varies with linear energy transfer (LET), tissue type and dose, but a variable RBE has not replaced the constant RBE of 1.1 in clinical treatment planning. We examined inter-patient variations in RBE for ten proton CSI patients. Variable RBE models were used to obtain RBE and RBE-weighted doses. RBE was quantified in terms of dose weighted organ-mean RBE ([Formula: see text] = mean RBE-weighted dose/mean physical dose) and effective RBE of the near maximum dose (D 2% ), i.e. RBE D2%  = [Formula: see text], where subscripts RBE and phys indicate that the D 2% is calculated based on an RBE model and the physical dose, respectively. Compared to the median [Formula: see text] of the patient population, differences up to 15% were observed for the individual [Formula: see text] values found for the thyroid, while more modest variations were seen for the heart (6%), lungs (2%) and brainstem (<1%). Large inter-patient variation in RBE could be correlated to large spread in LET and dose for these organs at risk (OARs). For OARs with small inter-patient variations, the results show that applying a population based RBE in treatment planning may be a step forward compared to using RBE of 1.1. OARs with large inter-patient RBE variations should ideally be selected for patient-specific biological or RBE robustness analysis if the physical doses are close to known dose thresholds.

Renal cell carcinoma (RCC) has been traditionally thought to be radioresistant. This retrospective cohort study aims to assess the outcomes of patients with spinal metastases from RCC treated with conventionally-fractionated external beam radiation therapy (cEBRT) in our institution.Patients diagnosed with histologically or radiologically-proven RCC who received palliative cEBRT to spinal metastases, using 3-dimensional conformal technique between 2009 and 2018 were reviewed. Local progression-free survival (PFS), overall survival (OS) and common terminology criteria for adverse events version 4.0-graded toxicity were assessed. Univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate for predictors associated with survivals.Thirty-five eligible patients with forty spinal segments were identified, with a median follow-up of 7 months (range, 0-47). The median equivalent dose in 2 Gy fractions (EQD2) was 32.5 Gy 10 (range, 12-39). Thirty-seven percent of patients underwent surgical intervention. At the time of last follow-up, all but 1 patient had died. Seven patients developed local progression, with the median time to local progression of 10.2 months. The median local PFS and OS were 3.3 and 4.8 months. There was no grade 3 or higher toxicity. A higher radiation dose (equivalent dose to 2 Gy fraction <32.5 Gy 10 vs ≥32.5Gy 10) (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.17-3.18; P-value (P) = .68) and spinal surgery (HR, 2.35; 95% CI, 0.53-10.29; P = .26) were not significantly associated with local PFS on univariable analysis. Multivariable analysis showed that higher Tokuhashi score (HR, 0.41; 95% CI, 0.19-0.88; P = .02), lower number of spinal segments irradiated (HR, 1.18; 95% CI, 1.01-1.37; P = .04) and use of targeted therapy (HR, 0.41; 95% CI, 0.18-0.96; P = .04) were independent predictors for improved OS.For an unselected group of patients with RCC, there is no significant association between higher radiation dose and improved local control following cEBRT. This may be due to their short survivals. With the use of more effective systemic therapy, including targeted therapy and immunotherapy, survival will likely be prolonged. A tailored-approach is needed to identify patients with good prognosis who may still benefit from aggressive local treatments.

Purpose/objective: Stereotactic ablative body radiotherapy (SABR) in multi-centre trials requires rigorous quality assurance to ensure safe and consistent treatment for all trial participants. We report results of vertebral SABR dosimetry credentialing for the ALTG/TROG NIVORAD trial., Material/methods: Centres with a previous SABR site visit performed axial film measurement of the benchmarking vertebral plan in a local phantom and submitted radiochromic film images for analysis. Remaining centres had on-site review of SABR processes and axial film measurement of the vertebral benchmarking plan. Films were analysed for dosimetric and positional accuracy: gamma analysis (>90% passing 2%/2mm/10% threshold) and ≤ 1 mm positional accuracy at target-cord interface was required., Results: 19 centres were credentialed; 11 had on-site measurement. Delivery devices included linear accelerator, TomoTherapy and CyberKnife systems. Five centres did not achieve 90% gamma passing rate. Of these, three were out of tolerance (OOT) in low (<5Gy) dose regions and > 80% passing rate and deemed acceptable. Two were OOT over the full dose range: one elected not to remeasure; the other also had positional discrepancy greater than 1 mm and repeat measurement with a new plan was in tolerance. The original OOT was attributed to inappropriate MLC constraints. All centres delivered planned target-cord dose gradient within 1 mm., Conclusion: Credentialing measurements for vertebral SABR in a multi-centre trial showed although the majority of centres delivered accurate vertebral SABR, there is high value in independent audit measurements. One centre with inappropriate MLC settings was detected, which may have resulted in delivery of clinically unacceptable vertebral SABR plans., Competing Interests: Declaration of Competing Interest Nicholas Hardcastle, Tomas Kron and Shankar Siva receive funding for an unrelated project from Varian Medical Systems., (Copyright © 2020. Published by Elsevier Ltd.)

Leptomeningeal malignancy complicates childhood cancers, including leukaemias, brain tumours, and solid tumours. In leukaemia, such malignancy is thought to invade leptomeninges via the vascular route. In brain tumours, dissemination from the primary tumour, before or after surgery, via CSF pathways is assumed; however, evidence exists to support the vascular route of dissemination. Success in treating leptomeningeal malignancy represents a rate-limiting step to cure, which has been successfully overcome in leukaemia with intensified systemic therapy combined with intra-CSF therapy, which replaced cranial radiotherapy for many patients. This de-escalated CNS-directed therapy is still associated with some neurotoxicity. The balanced benefit justifies exploration of ways to further de-escalate CNS-directed therapy. For primary brain tumours, standard therapy is craniospinal radiotherapy, but attendant risk of acute and delayed brain injury and endocrine deficiencies compounds post-radiation impairment of spinal growth. Alternative ways of treating leptomeninges by intensifying drug therapy delivered to CSF are being investigated-preliminary evidence suggests improved outcomes. This Review seeks to describe methods of intra-CSF drug delivery and drugs in use, and consider how the technique could be modified and additional drugs might be selected for this route of administration., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Significant efforts such as the Pediatric Proton/Photon Consortium Registry (PPCR) involving multiple proton therapy centers have been made to conduct collaborative studies evaluating outcomes following proton therapy. As a groundwork dosimetry effort for the late effect investigation, we developed a Monte Carlo (MC) model of proton pencil beam scanning (PBS) to estimate organ/tissue doses of pediatric patients at the Maryland Proton Treatment Center (MPTC), one of the proton centers involved in the PPCR. The MC beam modeling was performed using the TOPAS (TOol for PArticle Simulation) MC code and commissioned to match measurement data within 1% for range, and 0.3 mm for spot sizes. The established MC model was then tested by calculating organ/tissue doses for sample intracranial and craniospinal irradiations on whole-body pediatric computational human phantoms. The simulated dose distributions were compared with the treatment planning system dose distributions, showing the 3 mm/3% gamma index passing rates of 94%-99%, validating our simulations with the MC model. The calculated organ/tissue doses per prescribed doses for the craniospinal irradiations (1 mGy Gy -1 to 1 Gy Gy -1 ) were generally much higher than those for the intracranial irradiations (2.1 μGy Gy -1 to 0.1 Gy Gy -1 ), which is due to the larger field coverage of the craniospinal irradiations. The largest difference was observed at the adrenal dose, i.e. ∼3000 times. In addition, the calculated organ/tissue doses were compared with those calculated with a simplified MC model, showing that the beam properties (i.e. spot size, spot divergence, mean energy, and energy spread) do not significantly influence dose calculations despite the limited irradiation cases. This implies that the use of the MC model commissioned to the MPTC measurement data might be dosimetrically acceptable for patient dose reconstructions at other proton centers particularly when their measurement data are unavailable. The developed MC model will be used to reconstruct organ/tissue doses for MPTC pediatric patients collected in the PPCR.

Improvements in clinical care and therapy mean that more patients are diagnosed and living longer with vertebral metastases. Thus, they are at risk of the development of recurrence that requires re-irradiation. Normal tissues often recover some of the damage caused by the primary radiotherapy with time and specific normal tissues can tolerate a considerable retreatment radiation dose. However, the risk of normal tissue damage and the impact on the quality of life must be considered and should be done with maximum care and accuracy especially in the vertebral area. For many years conventional external beam radiation therapy was the standard treatment modality. Fortunately, with crucial technological progress in the field of radiation oncology we are able to integrate body imaging with accurate treatment delivery methods as stereotactic body radiotherapy to improve the efficacy, shorten the overall treatment time and potentially reduce treatment-related toxicities. A short description of re-irradiation strategy covering diagnostic procedures, volume delineation, dose reconstructions, treatment planning, and guidelines are outlined. Moreover, publications on vertebral bodies re-irradiation summarizing available knowledge about toxicity, dose-volume constraints, local control, and pain response are followed. Although the knowledge is limited to a series of a single institution, it shows that re-irradiation is an effective treatment for local control and pain response. Furthermore, treatment was also shown to be safe with low risk of spinal cord damage which is one of the most worrisome toxicity., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background: The spine is the most frequent location of bone metastases. Local treatment aims at palliation of pain and, given the increased likelihood of long-term cancer survival, at local control. Kyphoplasty and intraoperative radiotherapy (Kypho-IORT) provided instantaneous pain relief in 70% of patients at the first day after the intervention and resulted in local control rates of > 93% at 1 year in a recently conducted phase I/II trial. To assess its clinical value, we designed a phase III trial which tests Kypho-IORT against the most widespread standard-of-care, external beam radiotherapy (EBRT), in patients with painful vertebral metastases., Methods: This phase III study includes patients ≥50 years of age with up to 4 vertebral metastases and a pain score of at least 3/10 points on the visual/numeric analogy scale (VAS). Patients randomized into the experimental arm (A) will undergo Kypho-IORT (Kyphoplasty plus IORT with 8 Gy prescribed to 13 mm depth). Patients randomized into the control arm (B) will receive EBRT with either 30 Gy in 10 fractions or 8 Gy as a single dose. The primary end point is pain reduction defined as at least - 3 points on the VAS compared to baseline at day 1. Assuming that 40% of patients in the Kypho-IORT arm and 5% of patients in the control arm will achieve this reduction and 20% will drop out, a total of 54 patients will have to be included to reach a power of 0.817 with a two-sided alpha of 0.05. Secondary endpoints are evaluation of the percentage of patients with a pain reduction of at least 3 points at 2 and 6 weeks, local tumor control, frequency of re-intervention, secondary fractures/sintering, complication rates, skin toxicity/wound healing, progression-free survival (PFS), overall survival (OS) and quality of life., Discussion: This trial will generate level 1 evidence on the clinical value of a one-stop procedure which may provide instantaneous pain relief, long-term control and shortened intervals to further adjuvant (systemic) therapies in patients with spinal metastases., Trial Registration: Registered with ClinicalTrials.gov, number: NCT02773966 (Registration date: 05/16/2016).

Objective: Bone-seeking radiopharmaceuticals have the main role in the treatment of painful bone metastases. The aim of this study was to dosimetrically compare radiopharmaceuticals in use for bone pain palliation therapy and bone scan., Methods: The MCNPX code was used to simulate the radiation transport in a vertebral phantom. Absorbed fractions were calculated for monoenergetic electrons, photons and alpha particles. S values were obtained for radionuclides 32 P, 33 P, 89 Sr, 90 Y, 99m Tc, 117m Sn, 153 Sm, 166 Ho, 169 Er, 177 Lu, 186 Re, 188 Re, 223 Ra, 224 Ra and their progenies for target regions including the active marrow and the bone endosteum., Results: The results demonstrated the dependence of dosimetric parameters on the source or target size, particle energy and location of the source. The electron emitters including 33 P, 117m Sn, 169 Er and 177 Lu and 223 Ra as an α-emitter gave the lower absorbed dose to the active marrow. These radionuclides gave the highest values of the Relative Advantage Factor (RAF)., Conclusions: According to the results,  33 P, 117m Sn, 169 Er, 177 Lu and 223 Ra have fewer side effects on the active marrow than other investigated radionuclides. Therefore, these radionuclides may be a better choice for use in palliative radiotherapy.

Background: To evaluate the therapeutic outcomes in patients with bone metastases receiving radiotherapy (RT), it is important to use objective radiological response criteria. The aim of this study was to investigate the changes in pain and re-ossification after RT for painful vertebral bone metastases without paralysis by malignant spinal cord compression., Methods: The participants included 55 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. Bone modifying agents (BMAs) were administered in all patients. Follow-up assessments were done just before the start of RT and at 1, 2, 3, 4, and 6 months after RT. Radiological responses of irradiated vertebrae by RT were assessed by computed tomography (CT) using MD Anderson response classification criteria (MDA criteria) and the pain response was assessed by Numeric Rating Scale (NRS). Response was classified as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD)., Results: The rates of CR were 2%, 7%, 20%, 30%, and 56% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were 15%, 49%, 77%, 91%, and 91% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were significantly higher in patients with breast cancer than in patients with lung cancer (p = 0.043). At one month, there was an association between the NRS and radiological response assessed by MDA criteria. There was a significant trend that, with a better response, there were more patients without pain (p = 0.021)., Conclusions: Under BMAs administration, successful RT for vertebral bone metastases decreased pain and caused re-ossification. The MD Anderson criteria could be useful for assessment of radiological responses of irradiated vertebrae., (Copyright © 2018. Published by Elsevier B.V.)

Background: Tumor osseous pseudoprogression (PP), defined as an imaging-based transient increase in tumor size following treatment, was recently described in patients with spinal metastases following stereotactic body radiation therapy. Distinguishing PP from true tumor progression is critical., Objective: To describe the incidence, time of onset, and time range of PP following stereotactic body radiation therapy in patients treated for spinal metastases from either prostate cancer (PC) or renal cell carcinoma (RCC), and associated predictive factors., Methods: A retrospective study was conducted on our institution's cancer database from 2009 to 2015. Selection was based on single level, no prior radiation or surgery, ≥2 follow-up spine magnetic resonance imaging (MRI), and metastases arising from either PC or RCC. Gross tumor volume was contoured on pre- and up to 5 posttreatment MRIs. Patients were sorted into groups depending on gross tumor volume response: PP, non-PP, or progressive disease. Clinical and dosimetric variables were compared using either Fisher's exact test or Kruskal-Wallis analyses., Results: Forty-three spinal segments from 31 patients were analyzed. RCC and PC patients showed similar incidence of PP (∼37%). Whether the primary was lytic or sclerotic was a significant predictive factor with more PP in the lytic group (P = .0208). There was a trend of earlier PP onset in RCC (within 6-18 mo) as compared to PC; however, PC segments showed more time-confined presentation of PP (9-12 mo)., Conclusion: There was a higher incidence of PP in lytic compared to sclerotic primary tumor type. PP in spinal metastatic sites may have variable presentations depending on the primary cancer., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Background The aim of the study was to evaluate and compare four different external beam radiotherapy techniques of accelerated partial breast irradiation (APBI) considering target coverage, dose to organs at risk and overall plan quality. The investigated techniques were three dimensional conformal radiotherapy (3D-CRT), "step and shoot" (SS) and "sliding window" (SW) intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (RA). Patients and methods CT scans of 40 APBI patients were selected for the study. The planning objectives were set up according to the international recommendations. Homogeneity, conformity and plan quality indices were calculated from volumetric and dosimetric parameters of target volumes and organs at risk. The total monitor units and feasibility were also investigated. Results There were no significant differences in the coverage of the target volume between the techniques. The homogeneity indices of 3D-CRT, SS, SW and RA plans were 0.068, 0.074, 0.058 and 0.081, respectively. The conformation numbers were 0.60, 0.80, 0.82 and 0.89, respectively. The V50% values of the ipsilateral breast for 3D-CRT, SS, SW and RA were 47.5%, 40.2%, 39.9% and 31.6%, respectively. The average V10% and V40% values of ipsilateral lung were 13.1%, 28.1%, 28%, 36% and 2.6%, 1.9%, 1.9%, 3%, respectively. The 3D-CRT technique provided the best heart protection, especially in the low dose region. All contralateral organs received low doses. The SW technique achieved the best plan quality index (PQI). Conclusions Good target volume coverage and tolerable dose to the organs at risk are achievable with all four techniques. Taking into account all aspects, we recommend the SW IMRT technique for APBI.

Purpose: This study aimed to evaluate the impact on spine growth in children with medulloblastoma using either photon or electron craniospinal irradiation (CSI)., Methods and Materials: This was a single institution retrospective review of children who were treated with CSI for medulloblastoma. Spine growth was measured on magnetic resonance imaging scans at defined locations on the basis of a published predictive model of spine growth after CSI. Differences between spine growth in the anterior, middle, and posterior aspect of the designated vertebral segments were also assessed. Differences between the groups treated with photons or electrons were assessed with student's t test., Results: A total of 19 patients (10 patients treated with electrons and 9 with photons) with a median follow-up time of 45.5 months (confidence interval, 34.9-55.1 months) were evaluated. Patients treated with electrons were younger than those who received photons (5.1 years [range, 3.8-9.0 years] vs 9.6 years [range, 3.5-12.9 years]); however, there were no differences in other clinical characteristics, treatment, or follow-up between the groups. Spine growth rate for patients treated with electrons fit the predictive model (104% ± 5.2%), but patients treated with photons had growth that was faster than predicted by the model (150% ± 47%) and different from that observed with electrons. The differences between treatment the modalities were statistically significant (P = .03). For patients treated with photons, there were no statistical differences between the growth rate of the anterior vertebral body compared with the posterior aspect, but for patients treated with electrons, a faster spine growth in the anterior L1-L5 lumbar spine was observed compared with the posterior lumbar spine (3.90 vs 2.52 mm/year; P = .006) without differences in the cervical or thoracic spine., Conclusions: The use of electrons to treat the craniospinal axis in children with medulloblastoma resulted in no significant difference in spine growth compared with the predicted spine growth on the basis of previously published models using photons, but with a clinically insignificant faster spine growth rate in the anterior lumbar spine., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Long-term side effects of the treatments are common in survivors of irradiated pediatric brain tumors. Ionizing radiation in combination with surgery and chemotherapy during childhood may reduce vertebral height and bone mineral density (BMD), and cause growth failure. The aim of this study was to evaluate the late consequences of tumor treatments on vertebrae in survivors of childhood brain tumors., Methods: 72 adult survivors (mean age 27.8 years, standard deviation 6.7) of irradiated childhood brain tumor were studied by spinal magnetic resonance imaging (MRI) for vertebral abnormalities from the national cohort of Finland. Patients were treated in five university hospitals in Finland between the years 1970 and 2008. Subject height and weight were measured and body mass index (BMI) was calculated. The morphology and height/depth ratio of the vertebrae in the middle of the kyphotic thoracic curvature (Th8) and lumbar lordosis (L3) were examined. Vertebrae were analyzed by Genant's semiquantative (SQ) method and spinal deformity index (SDI) was calculated. BMD was measured by using dual X-ray absorptiometry., Results: 4.2% (3/72) of the patients had undiagnosed asymptomatic vertebral fracture and 5.6% (4/72) of patients had radiation-induced decreased vertebral body height. Male patients had flatter vertebrae compared with females. Patient age at the time of irradiation, BMI and irradiation area correlated to vertebral morphology differentially in males and females. BMD had no association with the vertebral shape. Patients who had received craniospinal irradiation were shorter than the general population., Conclusion: Childhood brain tumor survivors had a high number of vertebral abnormalities in young adulthood. Irradiation was associated with abnormal vertebral morphology and compromised final height. Male gender may predispose vertebrae to the side effects of irradiation., Competing Interests: The authors have declared that no competing interests exist.

Microgravity is one of the main threats to the health of astronauts. Pulsed electromagnetic fields (PEMFs) have been considered as one of the potential countermeasures for bone loss induced by space flight. However, the optimal therapeutic parameters of PEMFs have not been obtained and the action mechanism is still largely unknown. In this study, a set of optimal therapeutic parameters for PEMFs (50 Hz, 0.6 mT 50% duty cycle and 90 min/day) selected based on high-throughput screening with cultured osteoblasts was used to prevent bone loss in rats induced by hindlimb suspension, a commonly accepted animal model to simulate the space environment. It was found that hindlimb suspension for 4 weeks led to significant decreases in femoral and vertebral bone mineral density (BMD) and their maximal loads, severe deterioration in bone micro-structure, and decreases in levels of bone formation markers and increases in bone resorption markers. PEMF treatment prevented about 50% of the decreased BMD and maximal loads, preserved the microstructure of cancellous bone and thickness of cortical bone, and inhibited decreases in bone formation markers. Histological analyses revealed that PEMFs significantly alleviated the reduction in osteoblast number and inhibited the increase in adipocyte number in the bone marrow. PEMFs also blocked decreases in serum levels of parathyroid hormone and its downstream signal molecule cAMP, and maintained the phosphorylation levels of protein kinase A (PKA) and cAMP response element-binding protein (CREB). The expression level of soluble adenylyl cyclases (sAC) was also maintained. It therefore can be concluded that PEMFs partially prevented the bone loss induced by weightless environment by maintaining bone formation through signaling of the sAC/cAMP/PKA/CREB pathway. Bioelectromagnetics. 39:569-584, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

The use of routine spinal X-rays within chiropractic has a contentious history. Elements of the profession advocate for the need for routine spinal X-rays to improve patient management, whereas other chiropractors advocate using spinal X-rays only when endorsed by current imaging guidelines. This review aims to summarise the current evidence for the use of spinal X-ray in chiropractic practice, with consideration of the related risks and benefits. Current evidence supports the use of spinal X-rays only in the diagnosis of trauma and spondyloarthropathy, and in the assessment of progressive spinal structural deformities such as adolescent idiopathic scoliosis. MRI is indicated to diagnose serious pathology such as cancer or infection, and to assess the need for surgical management in radiculopathy and spinal stenosis. Strong evidence demonstrates risks of imaging such as excessive radiation exposure, overdiagnosis, subsequent low-value investigation and treatment procedures, and increased costs. In most cases the potential benefits from routine imaging, including spinal X-rays, do not outweigh the potential harms. The use of spinal X-rays should not be routinely performed in chiropractic practice, and should be guided by clinical guidelines and clinician judgement., Competing Interests: Not applicableNot applicableSDF is Deputy Editor-in-Chief of Chiropractic and Manual Therapies. He played no part in the assignment of this manuscript to Associate Editors or peer reviewers, and was blinded in the online editorial system for this manuscript from submission to final decision. Otherwise, the authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objective: This study investigated the influence of spatial overlap and radiographic length (RL) on the effective dose (ED) and organ dose for pediatric patients undergoing whole spine radiography using an auto-stitching digital radiography (DR) system., Methods: First, the system parameters were tested on a 10-year-old pediatric anthropomorphic phantom with a Shimadzu DR system, and the effects of the spatial overlap and RL on radiation doses were validated. The ED and organ dose were calculated on the basis of a Monte Carlo simulation program. Subsequently, 82 patients with adolescent idiopathic scoliosis were recruited. The spatial overlap and RL for each patient were modified to further investigate the dose reduction feasibility., Results: RL and ED were appropriately correlated on the basis of patients' height. For a patient measuring 158 cm, the Shimadzu DR system was equipped with a 17-inch detector with a cut-off RL of 75 cm. The phantom simulations indicated that ED was reduced to a minimum value of 0.188 ± 0.001 mSv with a high RL for RL < 75 cm. The minimum value increased to 0.300 ± 0.002 mSv for an RL of 75 cm and dropped to 0.222 ± 0.001 mSv for the maximum RL. By employing optimized RLs for patients, EDs were significantly reduced (p <  0.05). Moreover, ED reductions were higher when longer RLs were employed., Conclusion: A decrease in the spatial overlap and number of radiographic acquisitions by adjusting RLs when possible could reduce ED and almost all organ doses. This study emphasized the effects of RL on the radiation dose and provided useful guidance for modifying the RL for patients to reduce the whole spine radiography dose using a modern auto-stitching DR system., (Copyright © 2018. Published by Elsevier B.V.)

Thyroid cancer in children, the most common endocrine malignancy, shows aggressive behavior and has a high recurrence rate after surgical ablation. Radioactive iodine (RAI) treatment is the most effective primary modality for medical ablation of juvenile thyroid cancer, and leads to intentional hypothyroidism. Although several negative impacts of hypothyroidism have been reported in children in response to other antithyroid agents, the combined effects of RAI exposure and hypothyroidism, on growing bones specifically, are unknown. In this study, we investigated the effect of RAI-induced hypothyroidism on the long bones during the pubertal growth spurt using immature female rats. Female Sprague-Dawley rats were randomly divided into a control group, and an RAI-treated group fed with RAI (0.37 MBq/g body weight) twice via gavage. After 4 weeks, we observed a significantly-reduced serum free thyroxine level in the RAI group. The latter group also displayed decreased body weight gain compared to the control. In addition, the lengths of long bones, such as the leg bones and vertebral column, as well as bone mineral content, were reduced in the RAI-treated animals. Our results confirm the negative impacts of RAI-induced thyroid deficiency during puberty on longitudinal bone growth and bone mineralization.

Purpose: Assessing the stability of spinal metastases is critical for making treatment decisions. The spinal instability neoplastic score (SINS) was developed by the Spine Oncology Study Group to categorize tumor-related lesions; however, data describing its utility in predicting fractures in patients with spinal metastases are limited. The purpose of this study is to assess the validity of SINS in predicting new or worsening fracture after radiation therapy (RT) to spine metastases., Methods and Materials: This is a retrospective analysis of patients treated with conventional RT alone (median total dose, 30 Gy; range, 8-47 Gy; median number of fractions, 10; range, 1-25) for spinal metastasis at Dana-Farber/Brigham and Women's Cancer Center from 2006 to 2013. SINS was calculated for each lesion (range, 0-18). The primary endpoint was time from RT start to radiographically documented new or worsening fracture or last disease assessment., Results: A total of 203 patients and 250 lesions were included in analysis. The percentages of lesions with SINS of 0 to 6, 7 to 12, and 13 to 18 were 38.8%, 54.8%, and 6.4%, respectively. Of 250 lesions, 20.4% developed new or worsening fractures; 14.4% for SINS 0 to 6, 21.2% for SINS 7 to 12, and 50.0% for SINS 13 to 18. Multivariate analysis adjusted for sex, age, Eastern Cooperative Oncology Group, histology, and total dose indicated that, compared with stable lesions (SINS 0-6), potentially unstable lesions (SINS 7-12) demonstrated a greater likelihood of new or worsening fracture that was not statistically significant (hazard ratio, 1.66; 95% confidence interval, 0.85-3.22; P = .14), and unstable lesions (SINS 13-18) were significantly more likely to develop to new or worsening fracture (hazard ratio, HR,4.37, 95% confidence interval, 1.80-10.61; P = .001)., Conclusions: In this study of patients undergoing RT for spinal metastases, 20.4% developed new or worsening vertebral fractures. SINS is demonstrated to be a useful tool to assess fracture risk after RT., (Copyright © 2018. Published by Elsevier Inc.)

Introduction: The TEACHH score was developed to identify patients with predicted short (< 3 months) and long (> 1 year) life expectancy. We aimed to validate this model in an independent group of patients presenting for palliative spine radiotherapy and to compare it to alternate prognostic models., Methods: We retrospectively reviewed charts of 195 consecutive patients referred for palliative spine radiotherapy. Patients were grouped according to the number of risk factors from the TEACHH model, Chow model, and Oswestry Risk Index., Results: One hundred and eighty patients with a median age of 65 years were included. Follow-up was 5.8 months in all patients and 31.8 months in living patients. For the TEACHH model, patients in groups 1, 2, and 3 had a median (95% CI) overall survival (OS) of 22.3 (15.7-36.1), 4.9 (3.8-6.6), and 1.5 (0.8-5.4) months, respectively. Wilcoxon pairwise comparisons showed statistically different survival between groups 1 and 2, and 1 and 3. In the Chow model, patients in groups 1, 2, and 3 had a median (95% CI) OS of 16.1 (10.0-22.3), 5.9 (3.8-9.2), and 1.9 (1.2-2.5) months, respectively. There was a significant difference between all groups. The Oswestry Risk Index identified five prognostic groups with median OS (95% CI) ranging from 22.2 (12.9-30.2) to 2.1 (0.8-4.0) months. Only group 1 was statistically different from the others. Although the effect of age was small, the TEACHH model performed best with the inclusion of all parameters., Conclusions: The TEACHH model is useful to identify patients with spinal metastases with predicted short, intermediate, and long LE. Its prognostic ability is similar to the Chow model.

Background: The Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ) was developed as the first spine oncology-specific health-related quality of life (HRQOL) measure. This study evaluated the psychometric properties and clinical validity of the SOSGOQ in a diverse cohort of patients with spinal metastases., Methods: An international, multicenter, prospective observational cohort study including patients with spinal metastases who underwent surgery and/or radiotherapy was conducted by the AOSpine Knowledge Forum Tumor. Demographic, tumor, and treatment data were collected. HRQOL was evaluated using the SOSGOQ and Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) at baseline and fixed follow-up times. Construct validity was assessed using multitrait scaling analyses, confirmatory factor analyses, and correlation with the SF-36 and NRS pain score. Test-retest reliability was assessed in a subgroup of patients between 12 weeks after treatment and the retest 4 to 9 days later., Results: A total of 238 patients were enrolled at 9 centers across North America; 153 of these patients had HRQOL data available at 12 weeks after treatment. Multitrait scaling analyses and confirmatory factor analyses resulted in a refined version of the SOSGOQ with 4 domains and 4 single items. The revised SOSGOQ (SOSGOQ2.0) demonstrated strong correlations with SF-36 and the ability to discriminate between clinically distinct patient groups. Reliability of the SOSGOQ2.0 was demonstrated to be good, with an intraclass correlation coefficient ranging from 0.58 to 0.92 for the different domains., Conclusions: The SOSGOQ2.0 is a reliable and valid measure with which to evaluate HRQOL in patients with spinal metastases. It is recommended to use the SOSGOQ2.0 together with a generic HRQOL outcome measure to comprehensively assess HRQOL and increase sensitivity and specificity. Cancer 2018;124:1828-38. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., (© 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Purpose: Stereotactic body radiation therapy (SBRT) is a highly effective and potentially ablative treatment for complex spinal metastases. Recent data have suggested radiobiologic effects of SBRT that expand beyond the traditional concept of DNA damage. Antitumor immunity, vascular damage leading to tumor necrosis, and increased rates of tumor apoptosis have been implied; however, in-human evidence remains scarce. The present study reports unique pathologic confirmation of SBRT-induced biological effects within spinal metastases treated with preoperative SBRT., Methods and Materials: Ten patients with spinal metastases secondary to various solid tumors were treated with preoperative single-fraction SBRT (18 Gy) to the magnetic resonance imaging-defined macroscopic metastasis, followed by spinal stabilization within 24 hours. Perioperative samples of spinal metastases were obtained, and 6 patients also had a pre-SBRT biopsy specimen available for a matched comparison. The samples were stained for tumor necrosis on routine hematoxylin-eosin-stained slices and, subsequently, immunohistochemical staining for T cells (CD3+, CD4+, CD8+), natural killer cells (CD56+), endothelium (CD31+), and apoptotic activity (caspase-3)., Results: Perioperative biopsy specimens were obtained ∼6 hours (range 4.5-7.5) or 21 hours (range 18.5-22.5) after SBRT. Necrosis was observed in 83% of the 21-hour post-SBRT samples (5 of 6) compared with 0% of pre-SBRT biopsies (0 of 6) and 6-hour post-SBRT biopsies (0 of 4). Tumor cell apoptosis had increased greatly in the 21-hour post-SBRT samples compared with before and 6 hours after SBRT. The CD31+ vessel counts decreased after SBRT, as did mitotic activity. Both of the renal cell metastases displayed major decreases in vessel density. Desmoplastic reaction was visible in 67% (4 of 6) of the pre-SBRT samples compared with 100% (10 of 10) the post-SBRT samples. The T-cell and natural killer cell counts were relatively unaffected., Conclusions: High-dose single-fraction SBRT induced tumor necrosis, desmoplasia, and tumor apoptosis and decreased tumor vessel density within 24 hours, even in renal cell metastases. The role of immune cells seems limited in this early phase. These first-in-human results imply direct vascular and DNA damage mechanisms important in the clinical efficacy specific to spinal SBRT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Stereotactic body radiation therapy and stereotactic radiosurgery have become important treatment options for the treatment of spinal malignancies. A better understanding of dose tolerances with more conformal technology have allowed administration of higher and more ablative doses. In this review, the framework for approaching a patient with spinal metastases and primary tumors will be discussed as well as details on the delivery of this treatment.

Background: The objective of the present retrospective analysis was the response evaluation regarding bone density and stability of patients with osteolytic spinal bone lesions due to multiple myeloma after palliative radiotherapy (RT)., Patients and Methods: Patients with multiple myeloma who had undergone spinal RT from March 2003 to May 2016 were analyzed before and 3 and 6 months after RT. Assessment of spinal stability and bone density was performed using the internationally recognized Taneichi scoring system and measurement of bone density using computed tomography imaging-based Hounsfield units. For statistical analysis, we used the Bowker test, McNemar test, and κ statistics to detect possible asymmetries in the distribution of the Taneichi score over time. We used the Student t test for comparison of the density values (Hounsfield units) before and after treatment. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Additionally, overall survival was calculated using the Kaplan-Meier method., Results: We evaluated 130 patients (69% male; 31% female) with multiple myeloma and a median age of 58 years. The median follow-up period was 41 months. Before treatment, 51% of the lesions were classified as unstable. At 3 and 6 months after RT, this rate had decreased to 41% (P = .0047) and 24% (P = .2393), respectively. The computed tomography measurements showed a significant increase in bone density at 3 and 6 months after RT. Acute RT-related grade 1 and 2 complications were detected in 34% of patients. Late side effects (grade 1-2) were detected in 23% of the patients. No severe grade 3 or 4 acute or late toxicities were identified. The median overall survival was 19.7 months for all patients and 6.6 months for patients with a Karnofsky performance score of ≤ 70%., Conclusion: To the best of our knowledge, ours is the first report to analyze the bone density and stability in patients with multiple myeloma after RT using a validated scoring system and computed tomography imaging. Palliative RT is an effective method resulting in a significant increase in bone density for local response and stability without severe RT-related toxicity. Furthermore, recalcification could already be detected at 3 months after treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To compare the diagnostic performance of standard- and low-dose radiographs of the full-length lower extremity and spine., Methods: This study included 223 patients who visited our hospital and received full-length lower extremity standing radiographs and full-spine radiographs. We determined the dose area product (DAP) of each image, and effective doses (ED, mSv) were calculated based on the DAP. Subjective evaluation of the full-length radiographs was based on image quality, which was assessed by bony cortex and trabecula evaluation, and on diagnostic performance, which was assessed by leg length measurement. Subjective evaluation of the full-spine radiographs was based on image quality, which was assessed by viewing the vertebral endplate, pedicle and lateral border of vertebral body, and on diagnostic performance from measurement of Cobb's angle., Results: For the full-length view and the full-spine view both the mean DAP and ED values of the standard-dose group were significantly higher than those of the low-dose group (p < 0.05). Mean scores for subjective values did not significantly differ based on the radiation dosage (p-values, 0.15-0.99). The subjective value scores for the full-length view were 2.94-2.98 in the standard-dose group and 2.91-3.00 in the low-dose group. Of note, both groups had very high scores. Additionally, the diagnostic performance scores between the two groups were also very high (range from 2.92 to 3.00)., Conclusion: Reducing mAs by 50% of the standard dose does not affect the radiograph image quality or its clinical validity. Advances in knowledge: Radiation dose reduction (50% of the standard dose of mAs) in plain radiography of the full-length lower extremity and full spine do not affect the clinical validity and the image quality.

OBJECTIVE Spine stereotactic radiosurgery (SRS) is a safe and effective treatment for spinal metastases. However, it is unknown whether this highly conformal radiation technique is suitable at instrumented sites given the potential for microscopic disease seeding. The authors hypothesized that spinal decompression with instrumentation is not associated with increased local failure (LF) following SRS. METHODS A 2:1 propensity-matched retrospective cohort study of patients undergoing SRS for spinal metastasis was conducted. Patients with less than 1 month of radiographic follow-up were excluded. Each SRS treatment with spinal decompression and instrumentation was propensity matched to 2 controls without decompression or instrumentation on the basis of demographic, disease-related, dosimetric, and treatment-site characteristics. Standardized differences were used to assess for balance between matched cohorts. The primary outcome was the 12-month cumulative incidence of LF, with death as a competing risk. Lesions demonstrating any in-field progression were considered LFs. Secondary outcomes of interest were post-SRS pain flare, vertebral compression fracture, instrumentation failure, and any Grade ≥ 3 toxicity. Cumulative incidences analysis was used to estimate LF in each cohort, which were compared via Gray's test. Multivariate competing-risks regression was then used to adjust for prespecified covariates. RESULTS Of 650 candidates for the control group, 166 were propensity matched to 83 patients with instrumentation. Baseline characteristics were well balanced. The median prescription dose was 16 Gy in each cohort. The 12-month cumulative incidence of LF was not statistically significantly different between cohorts (22.8% [instrumentation] vs 15.8% [control], p = 0.25). After adjusting for the prespecified covariates in a multivariate competing-risks model, decompression with instrumentation did not contribute to a greater risk of LF (HR 1.21, 95% CI 0.74-1.98, p = 0.45). The incidences of post-SRS pain flare (11% vs 14%, p = 0.55), vertebral compression fracture (12% vs 22%, p = 0.04), and Grade ≥ 3 toxicity (1% vs 1%, p = 1.00) were not increased at instrumented sites. No instrumentation failures were observed. CONCLUSIONS In this propensity-matched analysis, LF and toxicity were similar among cohorts, suggesting that decompression with instrumentation does not significantly impact the efficacy or safety of spine SRS. Accordingly, spinal instrumentation may not be a contraindication to SRS. Future studies comparing SRS to conventional radiotherapy at instrumented sites in matched populations are warranted.

Object: Stereotactic body radiotherapy (SBRT) for vertebral metastases has emerged as a promising technique, offering high rates of symptom relief and local control combined with low risk of toxicity. Nonetheless, local failure or vertebral instability may occur after spine SBRT, generating the need for subsequent surgery in the irradiated region. This study evaluated whether there is an increased incidence of surgical complications in patients previously treated with SBRT at the index level., Methods: Based upon a retrospective international database of 704 cases treated with SBRT for vertebral metastases, 30 patients treated at 6 different institutions were identified who underwent surgery in a region previously treated with SBRT., Results: Thirty patients, median age 59 years (range 27-84 years) underwent SBRT for 32 vertebral metastases followed by surgery at the same vertebra. Median follow-up time from SBRT was 17 months. In 17 cases, conventional radiotherapy had been delivered prior to SBRT at a median dose of 30 Gy in median 10 fractions. SBRT was administered with a median prescription dose of 19.3 Gy (range 15-65 Gy) delivered in median 1 fraction (range 1-17) (median EQD2/10 = 44 Gy). The median time interval between SBRT and surgical salvage therapy was 6 months (range 1-39 months). Reasons for subsequent surgery were pain (n = 28), neurological deterioration (n = 15) or fracture of the vertebral body (n = 13). Open surgical decompression (n = 24) and/or stabilization (n = 18) were most frequently performed; Five patients (6 vertebrae) were treated without complications with vertebroplasty only. Increased fibrosis complicating the surgical procedure was explicitly stated in one surgical report. Two durotomies occurred which were closed during the operation, associated with a neurological deficit in one patient. Median blood loss was 500 ml, but five patients had a blood loss of more than 1 l during the procedure. Delayed wound healing was reported in two cases. One patient died within 30 days of the operation., Conclusion: In this series of surgical interventions following spine SBRT, the overall complication rate was 19%, which appears comparable to primary surgery without previous SBRT. Prior spine SBRT does not appear to significantly increase the risk of intra- and post-surgical complications.

The aim of this study is to explore the effect of timing of initiation of pulsed electromagnetic field (PEMF) therapy on bone mass, microarchitecture, and biomechanical properties, and to investigate receptor activator of NF-kB (RANK) expression in ovariectomized (OVX) rats. Sixty female Sprague-Dawley rats were randomly divided into two equal batches of three groups each (10 rats in each group). The first batch comprised of sham-operated (Sham-0 group), ovariectomized (OVX-0 group), and ovariectomized plus treated with PEMF starting from the day of OVX (Early PEMF group). The second batch comprised of sham-operated (Sham-12 group), ovariectomized (OVX-12 group), and ovariectomized plus treated with PEMF starting 12 weeks after OVX (Late PEMF group). Rats (whole body) in the early and late PEMF groups were exposed to PEMF (3.8 mT peak, 8 Hz pulse burst repetition rate). After 12 weeks of PEMF therapy, Early PEMF prevented OVX-induced deterioration in bone mineral density (BMD) and mechanical properties in lumbar vertebral body and femur, and deterioration in bone microarchitecture in lumbar vertebral body and proximal tibia. Late PEMF intervention only inhibited deterioration of BMD, bone microarchitecture, and mechanical properties in lumbar vertebral body. Both early and late PEMF therapy suppressed RANK protein expression in OVX rats without a concomitant effect on RANK mRNA expression. These results demonstrate that timing of initiation of PEMF therapy plays an important role in achieving optimal beneficial effects. The specific PEMF parameters may exert these favorable biological responses, at least partially, via inhibition of protein expression of RANK. Bioelectromagnetics. 38:456-465, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: A substantial number of patients with spinal metastases experience no treatment effect from palliative radiotherapy. Mechanical spinal instability, due to metastatic disease, could be associated with failed pain control following radiotherapy. This study investigates the relationship between the degree of spinal instability, as defined by the Spinal Instability Neoplastic Score (SINS), and response to radiotherapy in patients with symptomatic spinal metastases in a multi-institutional cohort., Methods and Materials: The SINS of 155 patients with painful thoracic, lumbar, or lumbosacral metastases from two tertiary hospitals was calculated using images from radiotherapy planning CT scans. Patient-reported pain response, available for 124 patients, was prospectively assessed. Pain response was categorized, according to international guidelines, as complete, partial, indeterminate, or progression of pain. The association between SINS and pain response was estimated by multivariable logistic regression analysis, correcting for predetermined clinical variables., Results: Of the 124 patients, 16 patients experienced a complete response and 65 patients experienced a partial response. Spinal Instability Neoplastic Score was associated with a complete pain response (adjusted odds-radio [ORadj] 0.78; 95% confidence interval [CI] 0.62-0.98), but not with an overall pain response (ORadj 0.94; 95% CI 0.81-1.10)., Conclusions: A lower SINS, indicating spinal stability, is associated with a complete pain response to radiotherapy. This supports the hypothesis that pain resulting from mechanical spinal instability responds less well to radiotherapy compared with pain from local tumor activity. No association could be determined between SINS and an overall pain response, which might indicate that this referral tool is not yet optimal for prediction of treatment outcome., Implications for Practice: Patients with stable painful spinal metastases, as indicated by a Spinal Instability Neoplastic Score (SINS) of 6 or lower, can effectively be treated with palliative external beam radiotherapy. The majority of patients with (impending) spinal instability, as indicated by a SINS score of 7 or higher, will achieve a (partial) response after palliative radiotherapy; however, some patients might require surgical intervention. Therefore, it is recommended to refer patients with a SINS score of 7 or higher to a spine surgeon to evaluate the need for surgical intervention., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of the article., (© AlphaMed Press 2017.)

Objectives: Contemporary dental radiology offers a wide spectrum of imaging methods but it also contributes to an increase in the participation of dental radiological diagnosis in the patient's exposure to ionizing radiation. The aim of this study is to determine the absorbed doses of the brain, spinal column, thyroid and eye lens for patients during panoramic radiography, cephalometric radiography and cone beam computed tomography (CBCT)., Material and Methods: The thermoluminescent dosimetry and anthropomorphic phantom was used for measuring the doses. The 15 panoramic, 4 cephalometric and 4 CBCT exposures were performed by placing high-sensitivity thermoluminescent detectors (TLD) in 18 anatomical points of the phantom., Results: The maximum absorbed dose recorded during performed measurements corresponds to the point representing the brainstem and it is 10 mGy. The dose value recorded by the TLD placed in the thyroid during CBCT imaging in relation to the panoramic radiography differs by a factor of 13.5., Conclusions: Cone beam computed tomography, in comparison with panoramic or cephalometric imaging technique, provides higher radiation doses to the patients. Int J Occup Med Environ Health 2017;30(5):705-713., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Purpose: Chordoma is a radioresistant tumor that presents a therapeutic challenge with spine involvement, as high doses of radiation are needed for local control while limiting dose to the spinal cord. The purpose of this study is to determine the efficacy and safety of single-fraction spine stereotactic body radiation therapy for the treatment of spine chordoma., Methods: A retrospective review of our institutional database from 2006 to 2013 identified 8 patients (12 cases) with chordoma of the spine who were treated with spine stereotactic body radiation therapy. Surgical resection was performed in 7 of the 12 cases. The treatment volume was defined by the bony vertebral level of the tumor along with soft tissue extension appreciated on magnetic resonance imaging fusion. Medical records and imaging were assessed for pain relief and local control. Treatment toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4.0., Results: Median age was 59 years (range, 17-91). Median target volume was 48 cm 3 (1-304), and median prescription dose was 16 Gy (11-16). Median conformality index was 1.44 (1.14-3.21), and homogeneity index was 1.12 (1.05-1.19). With a median follow-up time of 9.7 months (.5-84), local control was achieved in 75% of the cases treated. One patient developed limited grade 2 spinal cord myelopathy that resolved with steroids. There were no other treatment toxicities from spine stereotactic body radiation therapy., Conclusion: Single-fraction spine stereotactic body radiation therapy can be safely delivered to treat chordoma of the spine with the potential to improve pain symptoms. Although the early data are suggestive, long-term follow-up with more patients is necessary to determine the efficacy of spine stereotactic body radiation therapy in the treatment of chordoma of the spine.

This study investigated a single institution's experience with volumetric modulated arc therapy (VMAT) directed stereotactic ablative body radiotherapy (SABR) for vertebral metastases. From 2010 to 2014, 95 lesions of spinal metastases in 73 patients were treated with SABR using VMAT. Clinical local control, pain level, and use of steroid medication were employed to evaluate treatment responses. The majority (79%) of patients were treated with a radiation dose of 20 Gy in a single fraction. However, when normal tissue constraints could not be achieved, the dose was reduced to 18 Gy (11%) or 16 Gy (8%) in 1 fraction. At the median follow up of 12.7 months (mean 18.0, range 1-56 months), clinical local control was 97% (92 out of 95). There was a mean 81% (median 100%, range 28-100%) decrease in subjective pain score. Seventy-seven percent of patients had a decrease in narcotic pain medication use. Pain was completely resolved at the treatment site for 69% (66/95) of patients. Prior to the SABR treatment, 33% (31/95) of patients had epidural extension of tumor. Among patients with epidural involvement, 45% (14/31) exhibited neurologic impairment prior to treatment. Twenty-three percent (7/31) experienced spinal cord compression. Prior to treatment, 34 patients experienced some form of neurologic impairment. Of these patients, 24% (8/34) experienced improved motor functioning; the remaining 76% (26/34) of patients' neurological dysfunction were stable. Our results indicate the SABR regimen using VMAT technique is clinically effective in achieving clinical local control and palliation. This is the first publication reporting clinical outcomes of VMAT directed SABR.

We conducted a retrospective, nationwide multicenter study to evaluate the clinical outcomes of proton beam therapy for bone sarcomas of the skull base and spine in Japan. Eligibility criteria included: (i) histologically proven bone sarcomas of the skull base or spine; (ii) no metastases; (iii) ≥20 years of age; and (iv) no prior treatment with radiotherapy. Of the 103 patients treated between January 2004 and January 2012, we retrospectively analyzed data from 96 patients who were followed-up for >6 months or had died within 6 months. Seventy-two patients (75.0%) had chordoma, 20 patients (20.8%) had chondrosarcoma, and four patients (7.2%) had osteosarcoma. The most frequent tumor locations included the skull base in 68 patients (70.8%) and the sacral spine in 13 patients (13.5%). Patients received a median total dose of 70.0 Gy (relative biological effectiveness). The median follow-up was 52.6 (range, 6.3-131.9) months. The 5-year overall survival, progression-free survival, and local control rates were 75.3%, 49.6%, and 71.1%, respectively. Performance status was a significant factor for overall survival and progression-free survival, whilst sex was a significant factor for local control. Acute Grade 3 and late toxicities of ≥Grade 3 were observed in nine patients (9.4%) each (late Grade 4 toxicities [n = 3 patients; 3.1%]). No treatment-related deaths occurred. Proton beam therapy is safe and effective for the treatment of bone sarcomas of the skull base and spine in Japan. However, larger prospective studies with a longer follow-up are warranted., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective: To investigate the plan quality of tri-Co-60 intensity-modulated radiation therapy (IMRT) plans for spine stereotactic ablative radiotherapy (SABR)., Methods: A total of 20 patients with spine metastasis were retrospectively selected. For each patient, a tri-Co-60 IMRT plan and a volumetric-modulated arc therapy (VMAT) plan were generated. The spinal cords were defined based on MR images for the tri-Co-60 IMRT, while isotropic 1-mm margins were added to the spinal cords for the VMAT plans. The VMAT plans were generated with 10-MV flattening filter-free photon beams of TrueBeam STx ™ (Varian Medical Systems, Palo Alto, CA), while the tri-Co-60 IMRT plans were generated with the ViewRay ™ system (ViewRay inc., Cleveland, OH). The initial prescription dose was 18 Gy (1 fraction). If the tolerance dose of the spinal cord was not met, the prescription dose was reduced until the spinal cord tolerance dose was satisfied., Results: The mean dose to the target volumes, conformity index and homogeneity index of the VMAT and tri-Co-60 IMRT were 17.8 ± 0.8 vs 13.7 ± 3.9 Gy, 0.85 ± 0.20 vs 1.58 ± 1.29 and 0.09 ± 0.04 vs 0.24 ± 0.19, respectively. The integral doses and beam-on times were 16,570 ± 1768 vs 22,087 ± 2.986 Gy cm 3 and 3.95 ± 1.13 vs 48.82 ± 10.44 min, respectively., Conclusion: The tri-Co-60 IMRT seems inappropriate for spine SABR compared with VMAT. Advances in knowledge: For spine SABR, the tri-Co-60 IMRT is inappropriate owing to the large penumbra, large leaf width and low dose rate of the ViewRay system.

Ibandronate (IBN) and pulsed electromagnetic field (PEMF) have each shown positive effects for treating osteoporosis, but no study has evaluated the relative effects of these treatments combined. This study investigated the effects of IBN + PEMF on bone turnover, mineral density, microarchitecture, and biomechanical properties in an ovariectomized (OVX) rat model of osteoporosis. Fifty 3-month-old rats were randomly apportioned to receive a sham-operation (n = 10), or ovariectomy (n = 40). The latter group was equally divided as the model (OVX control) or to receive IBN, PEMF, or IBN + PEMF. Beginning the day after surgery, the IBN and IBN + PEMF groups received weekly subcutaneous IBN; the PEMF and IBN + PEMF groups were given daily PEMF during the same 12 weeks. After 12 weeks of treatments, biochemical parameters, bone mineral density (BMD), microarchitecture parameters, biomechanical properties, and some metabolic modulators that are involved in bone resorption were compared. The L5 lumbar vertebral body BMDs of the IBN, PEMF, and IBN + PEMF groups were 121.6%, 119.5%, and 139.6%; maximum loads were 111.4%, 112.7%, and 121.9%; and energy to failure was 130.8%, 129.2%, and 154.9% of the OVX model, respectively. The IBN + PEMF group had significantly lower levels of serum tartrate-resistant acid phosphatase 5b, and greater improvement in BMD, bone microarchitecture, and strength of the lumbar spine compared with monotherapy groups. Results showed that IBN + PEMF had a more favorable effect on the lumbar spine in this osteoporosis model than did either monotherapy. Bioelectromagnetics. 38:31-40, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)