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Background: This was a prespecified secondary analysis of a randomized trial that analyzed bone density and pain response following fractionated intensity-modulated radiotherapy (IMRT) versus three-dimensional conformal radiotherapy (3DCRT) for palliative management of spinal metastases., Methods/materials: Sixty patients were enrolled in the single-institutional randomized exploratory trial, randomly assigned to receive IMRT or 3DCRT (30 Gy in 10 fractions). Along with pain response (measured by the Visual Analog Scale (VAS) and Chow criteria), quantitative bone density was evaluated at baseline, 3, and 6 months in both irradiated and unirradiated spinal bodies, along with rates of pathologic fractures and vertebral compression fractures., Results: Relative to baseline, bone density increased at 3 and 6 months following IMRT by a median of 24.8% and 33.8%, respectively (p < 0.01 and p = 0.048). These figures in the 3DCRT cohort were 18.5% and 48.4%, respectively (p < 0.01 for both). There were no statistical differences in bone density between IMRT and 3DCRT at 3 (p = 0.723) or 6 months (p = 0.341). Subgroup analysis of osteolytic and osteoblastic metastases showed no differences between groups; however, mixed metastases showed an increase in bone density over baseline in the IMRT (but not 3DCRT) arm. The 3-month rate of the pathological fractures was 15.0% in the IMRT arm vs. 10.5% in the 3DCRT arm. There were no differences in pathological fractures at 3 (p = 0.676) and 6 (p = 1.000) months. The IMRT arm showed improved VAS scores at 3 (p = 0.037) but not 6 months (p = 0.430). Using Chow criteria, pain response was similar at both 3 (p = 0.395) and 6 (p = 0.732) months., Conclusions: This the first prospective investigation evaluating the impact of IMRT vs. 3DCRT on bone density. Along with pain response and pathologic fracture rates, significant rises in bone density after 3 and 6 months were similar in both cohorts. Future randomized investigations with larger sample sizes are recommended., Trial Registration: NCT, NCT02832830 . Registered 14 July 2016.

Purpose: Radiation therapy (RT) provides an important treatment approach in the palliative care of vertebral metastases, but radiation-induced toxicities in patients with advanced disease and low performance status can have substantial implications for quality of life. Herein, we prospectively compared toxicity profiles of intensity-modulated radiotherapy (IMRT) vs. conventional three-dimensional conformal radiotherapy (3DCRT)., Methods: This was a prospective randomized monocentric explorative pilot trial to compare radiation-induced toxicity between IMRT and 3DCRT for patients with spinal metastases. A total of 60 patients were randomized between November 2016 and May 2017. In both cohorts, RT was delivered in 10 fractions of 3 Gy each. The primary endpoint was radiation-induced toxicity at 3 months., Results: Median follow-up was 4.3 months. Two patients suffered from grade 3 acute toxicities in the IMRT arm, along with 1 patient in the 3DCRT group. At 12 weeks after treatment (t2), 1 patient reported grade 3 toxicity in the IMRT arm vs. 4 patients in the 3DCRT group. No grade 4 or 5 adverse events occurred in either group. In the IMRT arm, the most common side effects by the end of irradiation (t1) were grade 1-2 xerostomia and nausea in 8 patients each (29.6%), and dyspnea in 7 patients (25.9%). In the 3DCRT group, the most frequent adverse events (t1) were similar: grade 1-2 xerostomia (n = 10, 35.7%), esophagitis (n = 10, 35.8%), nausea (n = 10, 35.8%), and dyspnea (n = 5, 17.9%)., Conclusion: This is the first randomized trial to evaluate radiation-induced toxicities after IMRT versus 3DCRT in patients with vertebral metastases. This trial demonstrated an additional improvement for IMRT in terms of acute side effects, although longer follow-up is required to further ascertain other endpoints.

Background: This was a prespecified secondary analysis of a randomized trial, which analyzed bone density following stereotactic body radiotherapy (SBRT) versus conventional three-dimensional conformal radiotherapy (3DCRT) as part of palliative management of painful spinal metastases., Methods: Fifty-five patients were enrolled in this single-institutional randomized exploratory trial (NCT02358720). Participants were randomly assigned to receive SBRT (single-fraction 24 Gy) or 3DCRT (30 Gy/10 fractions). Quantitative bone density was evaluated at baseline, 3 and 6 months in both irradiated and unirradiated spinal bodies, along with rates of pathologic fractures and vertebral compression fractures., Results: As compared to baseline, bone density became significantly higher at 3 and 6 months following SBRT by a median of 33.8% and 72.1%, respectively (p < 0.01 for both). These figures in the 3DCRT cohort were 32.9% and 41.2%, respectively (p < 0.01 for both). There were no statistical differences in bone density between SBRT and 3DCRT at 3 (p = 0.629) or 6 months (p = 0.327). Subgroup analysis of osteolytic metastases showed an increase in bone density relative to baseline in the SBRT (but not 3DCRT) arm. Bone density in unaffected vertebrae did not show substantial changes in either group. The 3-month incidence of new pathological fractures was 8.7% in the SBRT arm vs. 4.3% in the 3DCRT arm., Conclusions: Despite high ablative doses in the SBRT arm, the significant increase in bone density after 3 and 6 months was similar to that of 3DCRT. Our trial demonstrated a moderate rate of subsequent pathological fracture after SBRT. Future randomized investigations with larger sample sizes are recommended., Trial Registration: www.clinicaltrials.gov : NCT02358720 on 9nd of February 2015.

Background: This study aimed to analyse the frequency and clinical relevance of sacral insufficiency fractures (SIFs) after high-dose carbon-ion based irradiation of sacral chordomas., Methods: A total of 56 patients were included in this retrospective study. Twenty one patients (37%) were treated with definitive radiotherapy (RT), and 35 patients (63%) received postoperative RT using carbon ions, either in combination with photons or as single-modality treatment (median radiation dose 66 Gy RBE, range 60-74 Gy). Follow-up examinations including MRI of the pelvis were performed at 3-monthly intervals in the first year and consecutively at 6-monthly intervals. Median follow-up was 35.5 months (range 2-83)., Results: SIFs were diagnosed in 29 patients (52%) after a median follow-up of 11 months (range 1-62 months). Most sacral fractures (79%) occurred within 2 years after RT. For the overall study population, the fracture-free survival probability amounted to values of 0.68 (95% CI, 0.53-0.79) after 1 year, 0.46 (95% CI, 0.31-0.60) after 2 years, and 0.31 (95% CI, 0.16-0.47) after 5 years. Statistical analysis showed no significant difference regarding the fracture rates between patients who received an operation and postoperative RT and patients treated with definitive RT. About one third of the patients with SIFs (34%; 10 of 29 patients) had associated clinical symptoms, most notably pain. All patients with symptomatic fractures required strong analgesics and often intensive pain management., Conclusions: Sacral fractures after high-dose carbon ion-based RT of sacral chordomas were shown to be a considerable radiogenic late effect, affecting about half of the treated patients. However, only one third of these fractures were clinically symptomatic requiring regular medical care and pain therapy. Further hazard factor analysis in the future with larger patient numbers will possibly enable the identification of high-risk patients for developing SIFs with the ultimate goal to prevent symptomatic fractures.

Background/aim: Quality of life (QOL) is becoming increasingly important to appraise the value of a particular oncologic intervention. This was a prespecified secondary analysis of a randomized trial (NCT02832830) of intensity-modulated radiotherapy (IMRT) versus conventional three-dimensional conformal radiotherapy (3DCRT) as part of palliative management of symptomatic spinal metastases. This study examined QOL, fatigue, emotional distress, and late toxicities between patients having received IMRT versus 3DCRT., Materials and Methods: Sixty patients were enrolled in this single-institutional randomized exploratory trial in which all patients received 30 Gy in 10 fractions. The EORTC QLQ-BM22, EORTC QLQ-FA13, and QSC-R10 questionnaires were utilized to evaluate QOL, fatigue, and emotional distress, respectively; endpoints were evaluated at baseline, and at 3, and 6 months. Late (6 months) toxicities were assessed according to the LENT-SOMA criteria., Results: Mean follow-up was 192 days (IQR=77-285). Although QOL was similar between groups, patients in the IMRT arm experienced lower physical (p=0.011) and emotional (p=0.017) fatigue at 6 months. Emotional distress was also lower in IMRT-treated patients after six months (p=0.039). Cohen's effect size confirmed the clinically significant improvement of these findings. Late toxicities occurred infrequently and were similar between arms., Conclusion: This is the first randomized study evaluating QOL between IMRT and 3DCRT to palliate vertebral metastases. IMRT resulted in reduced physical and emotional fatigue as well as emotional distress. IMRT should be further studied for these patients given these outcomes., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This was a prespecified secondary analysis of a randomized trial, which analyzed quality of life (QOL), fatigue, and emotional distress following stereotactic body radiotherapy (SBRT) versus conventional three-dimensional conformal radiotherapy (3DCRT) as part of palliative management of painful spinal metastases., Materials and Methods: Fifty-five patients were enrolled in this single-institutional randomized exploratory phase II trial (NCT02358720). Participants were randomly assigned to receive SBRT (single-fraction 24 Gy) or 3DCRT (30 Gy/10 fractions). QOL (EORTC QLQ-BM22), fatigue (EORTC QLQ FA13), and emotional distress (QSC-R10) at the end of radiotherapy, along with 3- and 6-month follow-up were assessed., Results: At all recorded time points, there were no significant QOL differences between cohorts, including painful sites, pain characteristics, functional impairment, or psychosocial aspects (p>0.05 for all). There were also no differences in all dimensions of fatigue between groups at each recorded time point (p>0.05 for all). Emotional distress was also similar at three (p=0.248) and six months (p=0.603)., Conclusion: Although these results demonstrate that SBRT does not cause worse QOL deteriorations compared to 3DCRT, larger randomized investigations are recommended to corroborate these findings., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: To report the primary endpoint of a randomized trial comparing pain response following palliative stereotactic body radiation therapy (SBRT) versus conventionally-fractionated 3D-conformal radiotherapy (3DCRT) for previously untreated spinal metastases., Methods: Fifty-five patients with histologically/radiologically confirmed painful spinal metastases were analyzed in this single-institutional, non-blinded, randomized explorative trial. Participants were randomly assigned (1:1) to receive single-fraction SBRT (24 Gy) or 3DCRT (30 Gy in 10 fractions). The primary endpoint was pain relief of >2 points on the visual analog scale (VAS) measured within the irradiated region at 3 months following radiotherapy completion. Other recorded parameters included pain response (per International Bone Consensus response definitions), use of concurrent medications and opioid usage (oral morphine equivalent dose, OMED). All parameters were assessed at baseline and at three and six months after RT. Intention-to-treat analysis was applied. This trial is registered with ClinicalTrials.gov, number NCT02358720., Findings: Despite no significant differences for VAS at 3 months between groups (p = 0.13), pain values decreased faster within this time period in the SBRT arm (p = 0.01). At 6 months following RT, significantly lower VAS values were reported in the SBRT group (p = 0.002). There were no differences in OMED consumption at 3 (p = 0.761) and 6 months (p = 0.174). There was a trend toward improved pain response in the SBRT arm at 3 months (p = 0.057), but significantly so after 6 months (p = 0.003). No patient in the SBRT group experienced grade ≥3 toxicities according to the Common Terminology Criteria for Adverse Events v.4.03., Conclusions: This randomized trial demonstrates the utility of palliative SBRT for spinal metastases, which was associated with a quicker and improved pain response. Larger ongoing randomized studies will assist in further addressing these endpoints., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The effect of radiotherapy, in particular the application of different multi-fraction schedules in the management of unstable spinal bone metastases (SBM), is incompletely understood. This study aims to compare the radiological response regarding various dose and fractionation schedules of radiotherapy in the palliative treatment of SBM., Methods: We retrospectively assessed 1047 patients with osteolytic SBM, treated with palliative radiotherapy at our department between 2000 and 2015. Lung cancer (40.2%), breast (16.7%) and renal cancer (15.2%) were the most common solid tumors in this study. Different common multi-fraction regimen (5x4Gy, 10x3Gy, 14 × 2.5Gy and 20x2Gy) were compared with regard to radiological response and recalcification at 3 and 6 months after radiotherapy. The Taneichi score was used for classification of osteolytic SBM., Results: Median follow up was 6.3 months. The median overall survival (OS) in the short-course radiotherapy (SCR) group using less than 10 treatment fractions was 5.5 months vs. 9.5 months in the long-course radiotherapy (LCR) group using in excess of 10 fractions (log rank p < .0001). Overall survival (OS) in the SCR group after 3 and 6 months was 66.8 and 49.1%, respectively vs 80.9 and 61.5%, respectively in the LCR group. 17.6% (n = 54/306) and 31.1% (n = 89/286) of unstable SBM were classified as stable in the SCR group at 3 and 6 months post radiotherapy, respectively (p < .001 for both). In the LCR group, 24.1% (n = 28/116) and 34.2% (n = 38/111) of unstable SBM were stabilized after 3 and 6 months, respectively (p < .001 for both)., Conclusions: Our study shows no significant difference in stabilization achieving recalcification rates between multi-fraction schedules (SCR vs. LCR) in the palliative management of unstable SBM. Both groups with multi-fraction regimen demonstrate a stabilizing effect following 3 and 6 months after radiotherapy.

Background: Stereotactic body radiation therapy (SBRT) using intensity-modulated radiotherapy (IMRT) with dose escalation by simultaneous integrated boost (SIB) can be a safe modality for treating spinal bone metastases with enhanced targeting accuracy and improve local tumor control., Methods/design: This is a single-center, prospective, randomized, controlled trial. One hundred and twenty patients with spinal bone metastases will receive palliative radiation therapy at the Heidelberg University Hospital. SBRT will be given in five or ten fractions with or without SIB. Four treatment arms are planned: IMRT with 30 Gy in ten fractions, IMRT with 30 Gy in ten fractions and SIB to 40 Gy, IMRT with 20 Gy in five fractions, and IMRT with 20 Gy in five fractions and SIB to 30Gy in five fractions will be compared. The target parameters will be measured at baseline level and at three and six months after radiation., Discussion: The primary endpoint of this study was to assess and compare the local tumor control (by means of different fractionation schedules and biological doses to the tumor area). Secondary endpoints are acute and chronic adverse events, pain relief, quality of life, and fatigue., Trial Registration: ClinicalTrials.gov, NCT02832765 . Registered on 27 July 2016.

Background: This retrospective analysis aimed to analyse the stability of spinal bone metastases in colorectal cancer (CRC) patients following radiotherapy (RT) by use of a validated score and to assess prognostic factors for stability and survival., Methods: Ninety-four patients with osteolytic spinal bone metastases from CRC were treated at the Department of Radiation Oncology at the University Hospital Heidelberg between 2000 and 2014. The stability of each affected vertebral body was assessed according to the validated Taneichi bone stability score on the basis of the treatment planning CT scan prior to RT and also based on the follow-up CT examinations at 3 and 6 months after RT. Additionally, bone survival rates (time between first day of RT and death from any cause) as well as prognostic factors for bone survival were evaluated for all study patients., Results: Before RT, 59 patients (63%) were rated unstable according to the Taneichi score. Pathological fractures within the irradiated region were diagnosed in 43 patients (46%) prior to RT. New fractures or progression of previously collapsed vertebrae were diagnosed in 4 patients (4%) after irradiation. Significant re-calcification and stabilization of former unstable bone metastases was only observed in 3/59 patients (3%) and 5/59 patients (9%). The median bone survival was 4.2 months (range 0.5-67.3 months) and 6 months after RT 61% of the patients were dead. Karnofsky performance score (KPS) (< 70% vs. ≥ 70%), chemotherapy and bisphosphonate therapy were predictive prognostic factors for bone survival., Conclusions: Our study population is characterized by poor bone survival and low re-calcification rates of unstable spinal bone lesions 3 and 6 months after RT. To avoid unnecessary hospitalisation and improve remaining QoL, short fractionated treatment schedules of RT may be prefered in this highly palliative situation, particularly for patients with a KPS < 70%.

Background: Metastatic bone disease is a common and severe complication in patients with advanced cancer. Radiotherapy (RT) has long been established as an effective local treatment for metastatic bone disorder. This study assesses the effects of RT combined with muscle-training exercises in patients with unstable bone metastases of the spinal column from solid tumors. The primary goal of this study is to evaluate the feasibility of muscle-training exercises concomitant to RT. Secondly, quality of life, fatigue, overall and bone survival, and local control will be assessed., Methods/design: This study is a single-center, prospective, randomized, controlled, explorative intervention study with a parallel-group design to determine multidimensional effects of a course of exercises concomitant to RT on patients who have unstable metastases of the vertebral column, first under therapeutic instruction and subsequently performed by the patients themselves independently for strengthening the paravertebral muscles. On the days of radiation treatment the patients will be given four different types of exercises to ensure even isometric muscle training of all the spinal muscles. In the control group progressive muscle relaxation will be carried out parallel to RT. The patients will be randomized into two groups: differentiated muscle training or progressive muscle relaxation with 30 patients in each group., Discussion: Despite the clinical experience that RT is an effective treatment for bone metastases, there is insufficient evidence for a positive effect of the combination with muscle-training exercises in patients with unstable bone metastases. Our previous DISPO-1 trial showed that adding muscle-training exercises to RT is feasible, whereas this was not proven in patients with an unstable spinal column. Although associated with several methodological and practical challenges, this randomized controlled trial is needed., Trial Registration: ClinicalTrials.gov, identifier: NCT02847754 . Registered on 27 July 2016.

Background: Radiation therapy (RT) of bone metastases provides an important treatment approach in palliative care treatment concepts. As a consequence of treatment, the extent of radiation-induced toxicity is a crucial feature with consequences to a patient's quality of life. In this context this study aims at reducing the extent of radiation-induced side effects and toxicity by assuming a better sparing of normal tissue with the use of intensity-modulated instead of conventionally delivered external beam radiotherapy., Methods/design: In this prospective, randomized, single-center trial for patients with spinal bone metastases, RT is performed as either image-guided intensity-modulated radiotherapy (10x3Gy) or conventionally fractionated external beam radiotherapy (10x3Gy). Afterwards radiation-induced toxicity will be assessed and compared 3 and 6 months after the end of radiation., Discussion: The aim of this pilot study is the evaluation of achievable benefits, with reduced radiation toxicity being the primary endpoint in the comparison of intensity-modulated radiotherapy versus conventional radiotherapy for patients with spinal bone metastases. Secondarily, bone re-calcification, quality of life, pain relief, spinal instability, and local control will be measured and compared between the two treatment groups., Trial Registration: ClinicalTrials.gov, NCT02832830 . Registered on 12 July 2016.

Purpose: To compare the effects of resistance training versus passive physical therapy on bone survival in the metastatic bone during radiation therapy (RT) as combined treatment in patients with spinal bone metastases. Secondly, to evaluate overall survival and progression-free-survival (PFS) as well as to quantify prognostic factors of bone survival after combined treatment., Methods: In this randomized trial 60 patients were allocated from September 2011 until March 2013 into one of the two groups: resistance training (group A) or passive physical therapy (group B) with thirty patients in each group during RT. We estimated patient survival using Kaplan-Meier survival method. The Wald-test was used to evaluate the prognostic importance of pathological fracture, primary site, Karnofsky performance status, localization of metastases, number of metastases, and cerebral metastases., Results: Median follow-up was 10 months (range 2-35). Bone survival showed no significant difference between groups (p = .303). Additionally no difference between groups could be detected in overall survival (p = .688) and PFS (p = .295). Local bone progression was detected in 16.7 % in group B, no irradiated bone in group A showed a local progression over the course (p = 0.019). In univariate analysis breast cancer, prostate cancer, and the presence of cerebral metastases had a significant impact on bone survival in group B, while no impact could be demonstrated in group A., Conclusions: In this group of patients with spinal bone metastases we were able to show that guided resistance training of the paravertebral muscles had no essential impact on survival concomitant to RT. Importantly, no local bone progression in group A was detected, nevertheless no prognostic factor for combined treatment could be evaluated., Trial Registration: Clinical trial identifier NCT 01409720 . Registered 8 February 2011.

Background: Adequate prediction of survival plays an important role in treatment decisions for patients with spinal bone metastases (SBM). Several prognostic factors are already used in daily clinical practice, but factors related to stability of SBM are still unknown. Therefore, we designed this study to identify these prognostic factors., Methods: We retrospectively assessed 915 patients from solid tumors with commonly metastased into the bone treated at our department between January 2000 and January 2012. Lung cancer (NSCLC), breast and renal cancer listed in Table 1 are the most common solid tumors with bone metastasis in this study. Prostate carcinoma was excluded due to osteoblastic SBM with no influence for stability. We calculated overall survival (OS) and bone survival (BS; time between first diagnosis of bone metastases until death) with the Kaplan-Meier method and assessed prognostic factors for BS with the log-rank test and a Cox regression model separately for patients with stable and unstable SBM., Results: Median follow-up was 9.3 months. OS after 6 months, 1, 2, and 5 years was 81, 62, 42, and 25 % in patients with stable SBM and 78, 57, 38, and 22 % in patients with unstable SBM (p = 0.851). BS was 57, 38, 22, and 5 % in the group of stable SBM after 6 months, 1, 2, and 5 years. For patients with unstable SBM BS after 6 months, 1, 2, and 5 years was 59, 39, 19, and 8 % (p = 0.755). In multivariate analysis we found male gender (HR = 1.27 [95 % CI 1.01-1.60], p = 0.04), Karnofsky performance status (KPS) <80 % (HR = 1.27 [95%CI 1.04-1.55], p = 0.02) and non-small cell lung cancer (NSCLC; HR = 2.77 [95%CI 1.99-3.86], p < 0.0001) to be independent prognostic factors for shortened survival in patients with stable SBM. Independent prognostic factors for unstable SBM were age per year (HR = 1.01 [95 % CI 1.0-1.02], p = 0.025), multiple SBM (HR = 1.35 [95 % CI 1.1-1.65], p = 0.003), and NSCLC (HR = 2.0 [95 % CI 1.43-2.80], p < 0.0001). Additionally, not wearing an orthopedic corset (HR = 0.77 [95 % CI 0.62-0.96], p = 0.02) was associated with prolonged BS in patients with unstable SBM and in both groups BS was significantly longer in patients without liver metastases (stable SBM: HR = 0.72 [95 % CI 0.56-0.92], p = 0.008; unstable SBM: HR = 0.71 [95 % CI 0.54-0.92], p = 0.01)., Conclusions: Survival was equal for patients with stable and unstable SBM. However, prognostic factors differed in both groups and stability should therefore be considered in treatment decision-making.

Purpose: This retrospective analysis aimed to evaluate the stability of spinal metastases in malignant melanoma patients following radiotherapy (RT), and to assess prognostic factors for survival., Methods: Forty-one patients with malignant melanoma and osteolytic spinal bone metastases were irradiated at the university clinics of Heidelberg and Mainz between July 2003 and October 2013. Three and six months after palliative RT, only 20 and 15 patients, respectively, were still alive and were therefore assessed for spinal stability using the Taneichi score based on CT imaging. Additionally, overall survival (OS) and bone survival (BS) rates as well as prognostic factors for BS were evaluated for all study patients., Results: Before RT, 19 patients (46.3%) were rated unstable. In the surviving patients, none of the unstable metastases were classified as stable 6 months after RT. Five-year OS was 23.3% and median BS was 4 months (range 0.5-29.8). Accordingly, only 36.6% of the patients were still alive 6 months after RT. Karnofsky performance score (KPS) &lt;70%, visceral metastases and more than one bone metastasis were significantly predictive of poor BS., Conclusions: Our study population was characterized by poor BS and a lack of benefit with regard to stabilization of initially unstable spinal bone metastases 3 and 6 months after RT. This applies in particular to patients with a KPS &lt;70%, visceral metastases and multiple bone metastases. Given the limited life expectancy, short fractionated treatment schedules of RT may be preferred in this population.

Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiotherapy (SBRT). As target geometry is complex, we compared SBRT plans using step-and-shoot intensity-modulated radiotherapy (IMRT), carbon ion RT, and proton RT. We prepared plans treating cervical, thoracic, and lumbar metastases for three different techniques--IMRT, carbon ion, and proton plans--to deliver a median single 24 Gy fraction such that at least 90% of the planning target volume (PTV) received more than 18 Gy and were compared for PTV coverage, normal organ sparing, and estimated delivery time. PTV coverage did not show significant differences for the techniques, spinal cord dose sparing was lowered with the particle techniques. For the cervical lesion spinal cord maximum dose, dose of 1% (D1), and percent volume receiving 10 Gy (V10Gy) were 11.9 Gy, 9.1 Gy, and 0.5% in IMRT. This could be lowered to 4.3 Gy, 2.5 Gy, and 0% in carbon ion planning and to 8.1 Gy, 6.1 Gy, and 0% in proton planning. Regarding the thoracic lesion no difference was found for the spinal cord. For the lumbar lesion maximum dose, D1 and percent volume receiving 5Gy (V5Gy) were 13.4 Gy, 8.9 Gy, and 8.9% for IMRT; 1.8 Gy, 0.7 Gy, and 0% for carbon ions; and 0 Gy, < 0.01 Gy, and 0% for protons. Estimated mean treatment times were shorter in particle techniques (6-7 min vs. 12-14 min with IMRT). This planning study indicates that carbon ion and proton RT can deliver high-quality PTV coverage for complex treatment volumes that surround the spinal cord.

Purpose: This retrospective analysis evaluated the outcome of patients with spinal bone metastases of renal cell cancer after radiotherapy (RT) in terms of stability and survival, using a validated scoring system for spinal stability assessment., Materials and Methods: The survival rates of 155 patients with bone metastases of renal cancer treated from January 2000 to January 2012 were determined. The stability of irradiated osteolytic lesions of the thoracic and lumbar spine was evaluated retrospectively using the Taneichi score and analyzed for predictive factors. The effects of therapy in terms of changes in neurological signs and tumor-related pain were recorded., Results: Follow-up with regular computed tomography (CT) was available for 28 patients, 14 with unstable metastases. One hundred thiry-two patients (85%) died during follow-up. RT could not improve the stability of vertebral bodies after 3 and 6 months. Consequently, none of the examined predictive factors such as age, number of bone metastases and systemic therapy showed a significant correlation with stability 6 months after RT. The median survival of all 155 patients after diagnosis of bone metastases was 12.9 months. Improvement of pain and neurological deficits occurred in 60%, and in 24% of the respective affected in all patients., Conclusions: RT was unable to improve the stability of vertebral metastases, probably due to the short overall survival, which resulted in an insufficient number of patients with evaluable follow-up. RT allowed reduction of pain and neurological deficits. A short fractionation schedule may be preferred in this situation.

Background: Clinical care of unstable spinal bone metastases in many centers often includes patient immobilization by means of an orthopedic corset in order to prevent pathological fractures. The aim of this retrospective analysis was to evaluate the incidence of pathological fractures after radiotherapy (RT) in patients with and without orthopedic corsets and to assess prognostic factors for pathological fractures in patients with spinal bone metastases., Methods: The incidence of pathological fractures in 915 patients with 2.195 osteolytic metastases in the thoracic and lumbar spine was evaluated retrospectively on the basis of computed tomography (CT) scans between January 2000 and January 2012 depending on prescription and wearing of patient-customized orthopedic corsets., Results: In the corset group, 6.8 and 8.0 % in no-corset group showed pathological fractures prior to RT, no significant difference between groups was detected (p = 0.473). After 6 months, patients in the corset group showed pathological fractures in 8.6 % and in no-corset group in 9.3 % (p = 0.709). The univariate and bivariate analyses demonstrated no significant prognostic factor for incidence of pathological fractures in both groups., Conclusions: In this analysis, we could show for the first time in more than 900 patients, that abandoning a general corset supply in patients with spinal metastases does not significantly cause increased rates of pathological fractures. Importantly, the incidence of pathological fracture after RT was small.

Background: Bone metastases are an important clinical issue in women with breast cancer. Particularly, unstable spinal bone metastases (SBM) are a major cause of severe morbidity and reduced quality of life (QoL) due to frequent immobilization. Radiotherapy (RT) is the major treatment modality and is capable of promoting re-ossification and improving stability. Since local therapy response is excellent, survival of these patients with unstable SBM is of high clinical importance. We therefore conducted this analysis to assess survival and to determine prognostic factors for bone survival (BS) in women with breast cancer and unstable SBM., Methods: A total population of 92 women with unstable SBM from breast cancer who were treated with RT at our department between January 2000 and January 2012 was retrospectively investigated. We calculated overall survival (OS) and BS (time between first diagnosis of bone metastases until death) with the Kaplan-Meier method and assessed prognostic factors for BS with a Cox regression model., Results: Mean age at first diagnosis of breast cancer was 60.8 years ± SD 12.4 years. OS after 1, 2 and 5 years was 84.8, 66.3 and 50 %, respectively. BS after 1, 2 and 5 years was 62.0, 33.7 and 12 %, respectively. An age > 50 years (p < .001; HR 1.036 [CI 1.015-1.057]), the presence of a single bone metastasis (p = .002; HR 0.469 [CI 0.292-0.753]) and triple negative phenotype (p < .001; HR 1.068 [CI 0.933-1.125]) were identified as independent prognostic factors for BS., Conclusions: Our analysis demonstrated a short survival of women with breast cancer and unstable SBM. Age, presence of a solitary SBM and triple-negative phenotype correlated with survival. Our results may have an impact on therapeutic decisions in the future and offer a rationale for future prospective investigations.

Background: Stereotactic body radiation therapy (SBRT)using intensity-modulated radiotherapy (IMRT) can be a safe modality for treating spinal bone metastasis with enhanced targeting accuracy and an effective method for achieving good tumor control and a rigorous pain response., Methods/design: This is a single-center, prospective randomized controlled trial to evaluate pain relief after RT and consists of two treatment groups with 30 patients in each group. One group will receive single-fraction intensity-modulated RT with 1 × 24 Gy, and the other will receive fractionated RT with 10 × 3 Gy. The target parameters will be measured at baseline and at 3 and 6 months after RT., Discussion: The aim of this study is to evaluate pain relief after RT in patients with spinal bone metastases by means of two different techniques: stereotactic body radiation therapy and fractionated RT. The primary endpoint is pain relief at the 3-month time-point after RT. Secondly, quality of life, fatigue, overall and bone survival, and local control will be assessed., Trial Registration: ClinicalTrials.gov identifier NCT02358720 (June 2, 2015).

Background: We designed this study to quantify the effects of radiotherapy (RT) on bone density as a local response in spinal bone metastases of women with breast cancer and, secondly, to establish bone density as an accurate and reproducible marker for assessment of local response to RT in spinal bone metastases., Methods: We retrospectively assessed 135 osteolytic spinal metastases in 115 women with metastatic breast cancer treated at our department between January 2000 and January 2012. Primary endpoint was to compare bone density in the bone metastases before, 3 months after and 6 months after RT. Bone density was measured in Hounsfield units (HU) in computed tomography scans. We calculated mean values in HU and the standard deviation (SD) as a measurement of bone density before, 3 months and 6 months after RT. T-test was used for statistical analysis of difference in bone density as well as for univariate analysis of prognostic factors for difference in bone density 3 and 6 months after RT., Results: Mean bone density was 194.8 HU ± SD 123.0 at baseline. Bone density increased significantly by a mean of 145.8 HU ± SD 139.4 after 3 months (p = .0001) and by 250.3 HU ± SD 147.1 after 6 months (p < .0001). Women receiving bisphosphonates showed a tendency towards higher increase in bone density in the metastases after 3 months (152.6 HU ± SD 141.9 vs. 76.0 HU ± SD 86.1; p = .069) and pathological fractures before RT were associated with a significantly higher increase in bone density after 3 months (202.3 HU ± SD 161.9 vs. 130.3 HU ± SD 129.2; p = .013). Concomitant chemotherapy (ChT) or endocrine therapy (ET), hormone receptor status, performance score, applied overall RT dose and prescription of a surgical corset did not correlate with a difference in bone density after RT., Conclusions: Bone density measurement in HU is a practicable and reproducible method for assessment of local RT response in osteolytic metastases in breast cancer. Our analysis demonstrated an excellent local response within metastases after palliative RT.

Background: The aim of this retrospective study was to evaluate the stability of spinal metastases in gynecologic cancer patients (pts) on the basis of a validated scoring system after radiotherapy (RT), to define prognostic factors for stability and to calculate survival., Methods: Fourty-four women with gynecologic malignancies and spinal bone metastases were treated at our department between January 2000 and January 2012. Out of those 34 were assessed regarding stability using the Taneichi score before, 3 and 6 months after RT. Additionally prognostic factors for stability, overall survival, and bone survival (time between first day of RT of bone metastases and death from any cause) were calculated., Results: Before RT 47% of pts were unstable and 6 months after RT 85% of pts were stable. Karnofsky performance status (KPS) >70% (p = 0.037) and no chemotherapy (ChT) (p = 0.046) prior to RT were significantly predictive for response. 5-year overall survival was 69% and 1-year bone survival was 73%., Conclusions: RT is capable of improving stability of osteolytic spinal metastases from gynecologic cancer by facilitating re-ossification in survivors. KPS may be a predictor for response. Pts who received ChT prior to RT may require additional bone supportive treatment to overcome bone remodeling imbalance. Survival in women with bone metastases from gynecologic cancer remains poor.

Purpose: This retrospective analysis was performed to evaluate osteolytic bone lesions of breast cancer in the thoracic and lumbar spine after radiotherapy (RT) in terms of stability using a validated scoring system., Methods: The stability of 157 osteolytic metastases, treated from January 2000 to January 2012, in 115 patients with breast cancer was evaluated retrospectively using the Taneichi score. Predictive factors for stability were analyzed and survival rates were calculated., Results: Eighty-five (54%) lesions were classified as unstable prior to RT. After 3 and 6 months, 109 (70%) and 124 (79%) lesions, respectively, were classified as stable. Thirty fractures were detected prior to RT, and after RT seven cases (4.5%) with pathologic fractures were found within 6 months. None of the examined predictive factors showed significant correlation with stability 6 months after RT. After a median follow-up of 16.7 months, Kaplan-Meier estimates revealed an overall survival of 83% after 5 years., Conclusion: The majority of patients showed an improved or unchanged stability of the involved vertebral bodies after 6 months. The patients showed only minor cancer-related morbidity during follow-up and reached comparably high survival rates.

Background: The aim of this trial was to compare the effects of resistance training versus passive physical therapy on quality of life (QoL), fatigue, and emotional distress outcomes during radiation therapy in patients with spinal bone metastases under radiotherapy (RT)., Methods: In this randomized trial, 60 patients were treated from September 2011 until March 2013 into one of the two groups: isometric resistance training or physical therapy with thirty patients in each group during RT. EORTC QLQ-BM22, EORTC QLQ-FA13, and FBK-R10 were assessed at baseline, three months, and six months after RT., Results: Psychosocial aspects in resistance training group (Arm A) were significantly improved after three (p = 0.001) and six months (p = 0.010). Other rated items of the QLQ-BM22 painful site, and pain characteristics were without significant differences. Functional interference showed a positive trend after six months (p = 0.081). After six months, physical fatigue (p = 0.013), and interference with daily life (p = 0.006) according to the QLQ-FA13 assessment improved in Arm A significantly. Emotional distress was in Arm A lower after six months (p = 0.016). The Cohen's effect size confirmed the clinically significant improvement of these findings., Conclusions: In this group of patients we were able to show that guided isometric resistance training of the paravertebral muscles can improve functional capacity, reduce fatigue and thereby enhance QoL over a 6-months period in patients with stable spinal metastases. The results offer a rationale for future large controlled investigations to confirm these findings., Trial Registration: Clinical trial identifier NCT01409720.

Background: To compare pain response outcomes for patients with spinal bone metastases treated with resistance training of the spinal musculature versus passive physical therapy during radiotherapy (RT)., Methods: In this randomized trial, 60 consecutive patients were treated from September 2011 until March 2013 within one of the two groups: resistance training (Arm A) or passive physical therapy (Arm B) with thirty patients in each group during RT. The course of pain according to visual analog scale (VAS), concurrent medication, and oral morphine equivalent dose (OMED) were assessed at baseline, three months, and six months after RT. Pain response was determined using International Bone Consensus response definitions., Results: The course of VAS in the intervention group (Arm A) was significantly lower both during and after RT (AUC, p < .001). The use of analgetic medication showed the same result, with significantly fewer analgetics being necessary both during and after RT in arm A (p < .001). In the course of time, the OMED decreased in arm A, but increased in arm B. After 6 month, 72.2% of patients in arm A, and 22.2% in arm B were responders (p = .014)., Conclusion: Our trial demonstrated that guided isometric resistance training of the paravertebral muscles can improve pain relief over a 6-months period in patients with stable spinal metastases. Importantly, the intervention was able to reduce OMED as well as concomitant pain medication. The trial is registered in Clinical trial identifier NCT 01409720 (http://www.clinicaltrials.gov/) since 2nd of August 2011.

Purpose: To compare the effects of resistance training versus passive physical therapy on bone density in the metastatic bone during radiation therapy (RT) as combined treatment in patients with spinal bone metastases. Secondly, to quantify pathological fractures after combined treatment., Material and Methods: In this randomized trial, 60 patients were allocated from September 2011 until March 2013 into one of the two groups: resistance training (group A) or passive physical therapy (group B) with thirty patients in each group during RT. Bone density in metastatic and non-metastatic vertebral bone was assessed at baseline, 3 and 6 months after RT., Results: Bone density in all metastases increased significantly by 28.3% (IQR 11.4-139.0) and 80.3% (IQR 32.6-250.6) after 3 and 6 months in group A (both p < 0.01). The bone density in group A was significantly increased compared to control group after 3 and 6months (both p < 0.01, median 59.7; IQR 21.1-98.3 and median 62.9; IQR -9.7 to 161.7). The bone density data in group B showed no significant increase over the course of time (p = 0.289, median 5.5, IQR 0.0-62.2 and p = 0.057, median 52.1, IQR 0.0-162.7). 23.3% of the patients in group A and 30.0% of the patients in group B had pathological fractures, no fracture was assigned to intervention, and no difference between groups after 3 and 6 months was observed (p = 0.592 and p = 0.604)., Conclusions: Our trial demonstrated that resistance training concomitant to RT can improve bone density in spinal bone metastases. This combined treatment is effective, practicable, and without side effects for patients. Importantly, the pathological fracture rate in the intervention group was not increased. The results offer a rationale for future large controlled investigations to confirm these findings., Trial Registration: Clinical trial identifier NCT01409720., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: To evaluate the local response according to stability after radiotherapy (RT) with a special focus on quality-of-life (QoL), fatigue, pain and emotional distress in patients with unstable spinal bone metastases., Methods: In this prospective trial, 30 patients were treated from September 2011 until March 2013. The stability of osteolytic metastases in the thoracic and lumbar spine was evaluated on the basis of the Taneichi-score after three and six months. EORTC QLQ-BM22, EORTC QLQ-FA13, and QSC-R10 were assessed at baseline, and three months after RT., Results: After 3 months, 25% (n = 6) and after 6 months 33.3% (n = 8) were classified as stable. QoL, fatigue, and emotional distress showed no difference over the course. The pain response 3 months after RT showed a significant difference (p < 0.001). Pathological fractures occurred in 8.3% of the patients (n = 2) within six months following RT., Conclusions: Our trial demonstrated that RT can improve stability in one third of patients over a 6-months period with unstable spinal metastases. Importantly, for these patients pain relief was detected but RT had no impact on QoL, fatigue, and emotional distress., Trial Registration: Clinical trial identifier NCT01409720.

Background: Spinal bone metastases are commonly diagnosed in cancer patients. The consequences are pain both at rest and under exercise, impairment of activities of daily life (ADL), reduced clinical performance, the risk of pathological fractures, and neurological deficits. The aim of this randomized, controlled pilot trial was to investigate the feasibility of muscle-training exercises in patients with spinal bone metastases under radiotherapy. Secondary endpoints were local control, pain response and survival., Methods: This study was a prospective, randomized, monocentre, controlled explorative intervention trial to determine the multidimensional effects of exercises for strengthening the paravertebral muscles. On the days of radiation treatment, patients in the control group were physically treated in form of respiratory therapy. Sixty patients were randomized between September 2011 and March 2013 into one of the two groups: differentiated resistance training or physical measure with thirty patients in each group., Results: The resistance training of the paravertebral muscles was feasible in 83.3% of patients (n = 25). Five patients died during the first three months. The exercise group experienced no measurable side effects. "Chair stand test" in the intervention group was significant enhanced with additionally improved analgesic efficiency. Patients in intervention group improved in pain score (VAS, 0-10) over the course (p < .001), and was significant better between groups (p = .003) after 3 months. The overall pain response showed no significant difference between groups (p = .158) There was no significant difference in overall and bone survival (survival from first diagnosed bone metastases to death)., Conclusions: Our trial demonstrated safety and feasibility of an isometric resistance training in patients with spinal bone metastases. The results offer a rationale for future large controlled investigations to confirm these findings.

Background and Purpose: For palliative care of spinal bone metastases, stability assessment is of crucial importance. Pathological fractures, instability-related patient immobility and the extent of bone metastasis have been reported to affect patient outcome and these parameters have therefore been used for treatment stratification. We report on stability-dependent fracture and survival rates in over 300 non-small cell lung cancer (NSCLC) patients., Materials and Methods: Data from 303 patients with 868 osteolytic metastases treated with radiotherapy (RT) between 2000 and 2012 were evaluated retrospectively., Results: In NSCLC patients with bone metastases only, the retrospective 6- and 12-month overall survival (OS) rates were 76.7 and 47.2%, respectively. In patients with additional non-bone distant metastases, these values were 60.0 and 34.0%, respectively. Survival rates were significantly lower in patients with multiple bone metastases and in those suffering pathological fractures (p=0.017). No significant impact of histological type, location of spinal lesions or treatment regime was detected. Furthermore, stability assessment revealed no influence of vertebral column stability on patient outcome (p=0.739)., Conclusion: Our analysis demonstrated a correlation between the pathological fractures of bone lesions, the number of bone metastases, additional distant metastases and survival. The results offer a rationale for future prospective investigations.

Objective: To determine whether preoperative parameters correlate with the postoperative functional outcome in para- and tetraplegic patients with lung, kidney, breast and prostate cancer and metastatic spinal cord compression (MSCC)., Methods: Information on 43 patients undergoing decompressive surgery and rehabilitation for MSCC was reviewed, including primary tumor, age, pre- and postoperative ambulation status, mobility subcategory of the Spinal Cord Injury Measure (mSCIM) and the Tokuhashi score. Differences between groups were analyzed by the nonparametric χ(2) test, and correlation coefficients (Spearman's rho) were computed., Results: Preoperative ambulation (p < 0.001), the American Spinal Injury Association Impairment Scale (p < 0.001) and the type of operation (p = 0.02) influenced the postoperative functional outcome. Any positive change in the mSCIM was influenced by preoperative ambulation (p < 0.001). Patients with breast carcinoma showed significantly more positive changes in the mSCIM compared with other tumors (p = 0.002). No correlation was found between the treatment categories of the Tokuhashi score and the preoperative ambulatory status (p = 0.13) or the change in ambulation status (p = 0.29)., Conclusion: The postoperative functional outcome of MSCC patients shows a linear association between the categories of the Tokuhashi score and the change in ambulation status. We recommend surgical decompression even in a palliative situation (Tokuhashi score 0-8) with the aim of optimizing the short-term rehabilitation outcome.

Background: The objective of this retrospective analysis is to systematically assess osseous lesions on the basis of a validated scoring system in terms of stability and fractures prior to and following radiotherapy in 338 lung cancer patients with bone metastases in the vertebral column., Methods: The stability of 338 patients with 981 osteolytic metastases in the thoracic and lumbar spine was evaluated retrospectively on the basis of the Taneichi-Score between January 2000 and January 2012., Results: 64% (215 patients) were classified stable prior to radiotherapy. Of the stable osseous metastases, none were rated unstable in the further course (p < 0.001, McNemar test). Of the 123 patients in whom the metastases were classified unstable prior to radiotherapy, 21 patients (17%) were classified stable after three months, and 30 patients (24%) stable after six months. A pathological fracture was diagnosed in 62 patients (18%) prior to radiotherapy. Regarding cases of osteolytic metastases of the vertebral bodies in which no fractures could be detected prior to the start of therapy, fractures occurred in 2% of all patients (n = 7) within six months following radiotherapy., Conclusions: Our analysis demonstrated that pathological fractures following radiotherapy occur in the very minority of vertebral lesions for patients with a favorable outcome. The use of a systematic radiological scoring system to classify osteolytic metastases of the vertebral column has shown to be feasible in daily routine. Prospective clinical trials are warranted in order to analyse, to what extent patients with osseous metastases can be mobilized by physiotherapy for strengthening the paravertebral muscles before radiotherapy effects can be measured by means of radiological recalcification.

Background: Osseous metastatic involvement of the spinal column affects many patients with a primary tumour disease of all entities. The consequences are pain both at rest and under exertion, impairments in going about day-to-day activities, diminished performance, the risk of pathological fractures, and neurological deficits. Palliative percutaneous radiotherapy is one of the therapeutical options available in this connection. The aim of this explorative study is to investigate the feasibility of muscle-training exercises and to evaluate the progression- and fracture-free survival time and the improvement of bone density, as well as to assess other clinical parameters such as pain, quality of life, and fatigue as secondary endpoints., Methods/design: This study is a prospective, randomized, monocentre, controlled explorative intervention study in the parallel-group design to determine the multidimensional effects of a course of exercises at first under physiotherapeutic instruction and subsequently performed by the patients independently for strengthening the paravertebral muscles of patients with metastases of the vertebral column parallel to their percutaneous radiotherapy. On the days of radiation treatment the patients in the control group shall be given physical treatment in the form of respiratory therapy and the so-called "hot roll". The patients will be randomized into one of the two groups: differentiated muscle training or physiotherapy with thirty patients in each group., Discussion: The aim of the study is to evaluate the feasibility of the training programme described here. Progression-free and fracture-free survival, improved response to radiotherapy by means of bone density, and clinical parameters such as pain, quality of life, and fatigue constitute secondary study objectives., Trial Registration: ClinicalTrials.gov: NCT01409720.