Telemedicine for Ketogenic Dietary Treatment in Refractory Epilepsy and Inherited Metabolic Disease: State of Play and Future Perspectives.

Ketogenic dietary therapies (KDT) are diets that induce a metabolic condition comparable to fasting. All types of KDT comprise a reduction in carbohydrates whilst dietary fat is increased up to 90% of daily energy expenditure. The amount of protein is normal or slightly increased. KDT are effective, well studied and established as non-pharmacological treatments for pediatric patients with refractory epilepsy and specific inherited metabolic diseases such as Glucose Transporter Type 1 Deficiency Syndrome. Patients and caregivers have to contribute actively to their day-to-day care especially in terms of (self-) calculation and (self-) provision of dietary treatment as well as (self-) measurement of blood glucose and ketones for therapy monitoring. In addition, patients often have to deal with ever-changing drug treatment plans and need to document occurring seizures on a regular basis. With this review, we aim to identify existing tools and features of telemedicine used in the KDT context and further aim to derive implications for further research and development.

Etiology-independent activation of the LTß-LTßR-RELB axis drives aggressiveness and predicts poor prognosis in HCC.

BACKGROUND AND AIMS: HCC is the most common primary liver tumor, with an increasing incidence worldwide. HCC is a heterogeneous malignancy and usually develops in a chronically injured liver. The NF-κB signaling network consists of a canonical and a noncanonical branch. Activation of canonical NF-κB in HCC is documented. However, a functional and clinically relevant role of noncanonical NF-κB and its downstream effectors is not established. APPROACH AND RESULTS: Four human HCC cohorts (total n = 1462) and 4 mouse HCC models were assessed for expression and localization of NF-κB signaling components and activating ligands. In vitro , NF-κB signaling, proliferation, and cell death were measured, proving a pro-proliferative role of v-rel avian reticuloendotheliosis viral oncogene homolog B (RELB) activated by means of NF-κB-inducing kinase. In vivo , lymphotoxin beta was identified as the predominant inducer of RELB activation. Importantly, hepatocyte-specific RELB knockout in a murine HCC model led to a lower incidence compared to controls and lower maximal tumor diameters. In silico , RELB activity and RELB-directed transcriptomics were validated on the The Cancer Genome Atlas HCC cohort using inferred protein activity and Gene Set Enrichment Analysis. In RELB-active HCC, pathways mediating proliferation were significantly activated. In contrast to v-rel avian reticuloendotheliosis viral oncogene homolog A, nuclear enrichment of noncanonical RELB expression identified patients with a poor prognosis in an etiology-independent manner. Moreover, RELB activation was associated with malignant features metastasis and recurrence. CONCLUSIONS: This study demonstrates a prognostically relevant, etiology-independent, and cross-species consistent activation of a lymphotoxin beta/LTßR/RELB axis in hepatocarcinogenesis. These observations may harbor broad implications for HCC, including possible clinical exploitation.

Integrated Telehealth Infrastructure for Ambulatory Stroke Pathway Tyrol.

BACKGROUND: The Integrated Treatment Pathway Stroke Tyrol was introduced for the care of people after an acute stroke event and includes four phases: acute prehospital care, inpatient treatment, inpatient rehabilitation and ambulatory, outpatient rehabilitation. For the 4th phase, the ambulatory rehabilitation of patients after discharge, the ICT platform "StrokeNet Tyrol" was established. METHODS: Requirements and processes along the pathway and between the interdisciplinary team were taken into account for implementation based on a modular software architecture. Flexible rights and role concept was developed to support efficient collaboration of the heterogenic professions. RESULTS: The routine usage of 342 users with 8 different roles, 2,219 registered patient cases within the last 4 years and first results of the integrated benchmarking solution give a positive impression regarding feasibility and effectiveness. CONCLUSION: To this point, a comprehensive infrastructure for the Ambulatory Tyrolean Stroke Pathway has been established. Results from outcome analyses and comparative studies could help to further improve usability and to expand the area of application for other indications.

Specific Targeting of Antiapoptotic Bcl-2 Proteins as a Radiosensitizing Approach in Solid Tumors.

Avoidance of therapy-induced apoptosis is a hallmark of acquired resistance towards radiotherapy. Thus, breaking resistance still challenges modern cancer therapy. The Bcl-2 protein family is known for its regulatory role in apoptosis signaling, making Bcl-2, Mcl-1 and Bcl-xL promising targets. This study evaluates the effects of highly specific inhibitors for Bcl-xL (WEHI-539), Bcl-2 (ABT-199) and Mcl-1 (S63845) as radiosensitizers. Covering a broad spectrum of solid tumors, Non-Small-Cell Lung Cancer (NSCLC), Head and Neck Squamous Cell Carcinoma (HNSCC) and synovial sarcoma cell lines were exposed to fractionated radiation as standard therapy with or without Bcl-2 protein inhibition. Protein expression was detected by Western blot and cell death was assessed by flow cytometry measuring apoptosis. In contrast to NSCLC, a high level of Bcl-xL and its upregulation during radiotherapy indicated radioresistance in HNSCC and synovial sarcoma. Radioresistant cell lines across all entities benefited synergistically from combined therapy with Bcl-xL inhibition and fractionated radiation. In NSCLC cell lines, Mcl-1 inhibition significantly augmented radiotherapy independent of the expression level. Our data suggest that among antiapoptotic Bcl-2 proteins, targeting Bcl-xL may break resistance to radiation in HNSCC, synovial sarcoma and NSCLC in vitro. In NSCLC, Mcl-1 might be a promising target that needs further investigation.

µRA-A New Compact Easy-to-Use Raman System for All Hydrogen Isotopologues.

We have developed a new compact and cost-efficient Laser-Raman system for the simultaneous measurement of all six hydrogen isotopologues. The focus of this research was set on producing a tool that can be implemented in virtually any existing setup providing in situ process control and analytics. The "micro Raman (µRA)" system is completely fiber-coupled for an easy setup consisting of (i) a spectrometer/CCD unit, (ii) a 532 nm laser, and (iii) a commercial Raman head coupled with a newly developed, tritium-compatible all-metal sealed DN16CF flange/Raman window serving as the process interface. To simplify the operation, we developed our own software suite for instrument control, data acquisition, and data evaluation in real-time. We have given a detailed description of the system, showing the system's capabilities in terms of the lower level of detection, and presented the results of a dedicated campaign using the accurate reference mixtures of all of the hydrogen isotopologues benchmarking µRA against two of the most sensitive Raman systems for tritium operation. Due to its modular nature, modifications that allow for the detection of various other gas species can be easily implemented.

Accurate Reference Gas Mixtures Containing Tritiated Molecules: Their Production and Raman-Based Analysis.

Highly accurate, quantitative analyses of mixtures of hydrogen isotopologues-both the stable species, H2, D2, and HD, and the radioactive species, T2, HT, and DT-are of great importance in fields as diverse as deuterium-tritium fusion, neutrino mass measurements using tritium ß-decay, or for photonuclear experiments in which hydrogen-deuterium targets are used. In this publication we describe a production, handling, and analysis facility capable of fabricating well-defined gas samples, which may contain any of the stable and radioactive hydrogen isotopologues, with sub-percent accuracy for the relative species concentrations. The production is based on precise manometric gas mixing of H2, D2, and T2. The heteronuclear isotopologues HD, HT, and DT are generated via controlled, in-line catalytic reaction or by ß-induced self-equilibration, respectively. The analysis was carried out using an in-line intensity- and wavelength-calibrated Raman spectroscopy system. This allows for continuous monitoring of the composition of the circulating gas during the self-equilibration or catalytic evolution phases. During all procedures, effects, such as exchange reactions with wall materials, were considered with care. Together with measurement statistics, these and other systematic effects were included in the determination of composition uncertainties of the generated reference gas samples. Measurement and calibration accuracy at the level of 1% was achieved.

Extracranial Stereotactic Body Radiotherapy in Oligometastatic or Oligoprogressive Breast Cancer.

Purpose/Objective: Oligometastatic disease (OMD) and oligoprogressive disease (OPD) describe tumor states with a limited metastasization. In contrast to other disease states, treatment of OMD or OPD has not yet become common for breast cancer. We sought to understand the outcomes and toxicities of this treatment paradigm. Material/Methods: We retrospectively analyzed female breast cancer patients with OMD (≤3 metastases) or OPD (1 progressive lesion) who received stereotactic body radiotherapy (SBRT) for their respective extracranial metastatic lesions between 01/2002 and 07/2019. Survival analysis was performed using the Kaplan-Meier method with log-rank test being used for evaluation of significance. Cox regression was used to detect prognostic outcome factors. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). Results: Forty-six patients (70% OMD; 30% OPD) with 58 lesions met criteria for inclusion. The majority of treatments (34 out of 58; 58.6%) were delivered from 2017 to 2018. Treatment sites were bone, liver, lung [n = 19 (33%) for each site], and adrenal gland [n = 1 (1%)]. Median biologically effective dose (BED at α/ß = 10) was 81.6 Gy (range: 45-112.5 Gy) and median planning target volume was 36.60 mL (range: 3.76-311.00 mL). At 2 years, local control (LC) was 89%, distant control (DC) was 44%, progression free survival (PFS) was 17% and overall survival (OS) was 62%. Multivariate analysis identified the diagnosis of a solitary metastasis as an independent prognostic factor for superior DC (HR = 0.186, CI [0.055; 0.626], p = 0.007) and PFS (HR = 0.363, CI [0.152; 0.863], p = 0.022). OS was independently inferior for patients treated at a higher age (HR = 5.788, CI [1.077; 31.119] p = 0.041). Nine (15.5%) grade I° and one (1.7%) grade II° toxicities were recorded, with no grade III° or higher toxicities. Conclusion: Extracranial SBRT in breast cancer patients with OMD or OPD was well-tolerated with excellent LC. SBRT should especially be offered to younger OMD and OPD breast cancer patients with only one metastasis. The increase in utilization since 2017 points toward a growing acceptance of SBRT for OMD and OPD in breast cancer.

Percutaneous Endoscopic Gastrostomy Tube Placement in Patients with Head and Neck Cancer Treated with Radiotherapy.

BACKGROUND AND AIM: The primary aim of our study was to evaluate percutaneous endoscopic gastrostomy (PEG) tube placement depending on body weight and body mass index in patients undergoing radiotherapy (RT) for head and neck cancer (HNC). A secondary aim was to evaluate the course of weight change following PEG placement. METHODS: We retrospectively reviewed the medical records of 186 patients with HNC undergoing radiotherapy (RT) or chemoradiotherapy (CRT) at our institution between January 2010 and August 2017. Initial weight and nutritional intake were analyzed prior to RT initiation and then followed throughout treatment until completion. Based on these data, the indication of PEG placement was determined. Medical records were also reviewed to analyze PEG-related acute toxicities. RESULTS: A total of 186 patients met inclusion criteria. Patients were most commonly male (n=123, 66.1%) with squamous cell carcinoma (n=164, 88.2%). Patients who had dysphagia prior to treatment initiation as well as patients with a BMI <18.5 kg/m2 needed PEG placement earlier during the treatment course. Low-grade toxicities related to PEG insertion were observed in 10.7% patients, with peristomal pain and redness adjacent to the PEG tube insertion site being most common. High-grade toxicities, such as peritonitis and organ injury, were found in 4.9% of patients. CONCLUSION: Underweight patients and those with preexisting dysphagia should be closely screened during RT for weight loss and decreased oral intake. For weight loss greater than 4.5% during the treatment of HNC, early PEG-tube placement should be considered. Further prospective studies are needed to confirm these findings, and delineate a scoring system for timing of PEG use (prophylactic vs reactive) as well as assess the quality of life in patients with HNC who receive PEG placement.

Age-dependent hemato- and nephrotoxicity in patients with head and neck cancer receiving chemoradiotherapy with weekly cisplatin.

BACKGROUND AND PURPOSE: In cases of simultaneous chemoradiotherapy (CRT), early recognition of toxic side effects is important, as drug discontinuation may prevent further injury. It appears favorable to undertake further steps to investigate whether patient subgroups behave differently depending on their toxicity profile. METHODS: We retrospectively analyzed 125 consecutive patients with non-metastasized carcinoma of the head and neck who were treated with CRT (cisplatin 40 mg/m2 weekly) in 2013/2014. Patients were planned to receive six cycles of cisplatin. Statistical analyses were performed using the chi2 test, t-test, Kaplan-Meier method, and the log-rank test, as appropriate. RESULTS: Eighty-six patients did not reach the intended sixth cycle (68.8%; 60.0% of whom were ≥60 years, p < 0.05). Acute kidney injury (glomerular filtration rate <60 mL/min/1.73m2) was the most common reason for drug discontinuation (26.7%; 82.6% of whom were ≥60 years; p < 0.01), followed by leukopenia <3/nL (23.3%; 75% of whom were <60 years; p < 0.01) and infection (11.6%). Patients who underwent ≥5 cycles were associated with prolonged overall survival and metastasis-free survival after CRT (p < 0.02; median follow-up 24 months), especially patients <60 years. CONCLUSION: Acute kidney injury was the most common side effect in patients ≥60 years, whereas leukopenia characteristically occurred significantly more often in younger patients. Discontinuing cisplatin during CRT was associated with a worse outcome, especially in patients <60 years.

Active-Scanned Protons and Carbon Ions in Cancer Treatment of Patients With Cardiac Implantable Electronic Devices: Experience of a Single Institution.

Background: Ionizing radiation was shown to be able to influence the function of cardiac implantable electronic devices (CIED's) leading to malfunctions with potentially severe consequences. Those effects presumably correlate with beam energy and neutron production. Thus, particle facilities are commonly cautious to treat patients with CIED's with particles, but substantial evidence is lacking. Methods and Materials: In total 31 patients were investigated, who have been treated at the Heidelberg Ion-Beam Therapy Center (HIT) from September 2012 to February 2019 with protons and carbon ions in active-scanning technique. All CIED's were checked after every single irradiation by the department of cardiology. The minimum distance between the CIED and the planning target volume (PTV), the 10% isodose and the single beam in Beam's Eye View (BEV) was analyzed for 12 patients. Results: In total, 31 patients received 32 courses of radiotherapy (RT). Twenty-two received treatment with carbon ion beam and ten with proton beam. The cumulative number of fractions was 582, the cumulative number of documented controls after RT was 504 (87%). Three patients had an implantable cardioverter-defibrillator (ICD) and 28 patients had a pacemaker at the time of treatment. Seven patients had a heart rate of ≤30/min. The majority of patients (69%) were treated for tumors of the head and neck. The median minimum distance between CIED and PTV, 10% isodose and the single beam on BEV was 13.4, 11.6, and 8.3 cm, respectively. There were no registered events associated with the treatment in this evaluation. Conclusion: Treatment of CIED-patients with protons and carbon ions applied with active raster scanning technique was safe without any incidents in our single center experience. Monitoring after almost every fraction provided systematic and extensive data. Further investigations are necessary in order to form reliable guidelines, which should consider different modes of beam application, as active scanning supposedly provides a greater level of safety from malfunctions for patients with CIED undergoing particle irradiation.

eHealth Service for Integrated Care and Outpatient Rehabilitation - Pilot Application of the Tyrol Stroke Pathway.

BACKGROUND: Stroke is one of third most common causes of death and the main cause for permanent disabilities. The Tyrol Stroke Pathway covers, all steps from stroke onset to outpatient rehabilitation. OBJECTIVES: The main objective of this paper is to describe how the paper-based documentation in the outpatient rehabilitation can be implemented in an eHealth service for integrated care. METHODS: First a state analysis followed by a requirement analysis was performed. An interactive mock-up was designed for further discussion with the stakeholders. After the implementation of the system the evaluation was performed in two steps: feedback from a virtual test phase and a pilot operation was analyzed. RESULTS: First experiences during the virtual test phase with key stakeholders of the therapy pathway showed a high level of acceptance. Users reported an improvement in the communication and documentation processes. CONCLUSION: Initial results illustrate how a shift from paper-based documentation to an integrated eHealth service can improve communication and documentation in an independent therapy network.

Radiation-induced acute toxicities after image-guided intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for patients with spinal metastases (IRON-1 trial) : First results of a randomized controlled trial.

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.

Randomized phase II trial evaluating pain response in patients with spinal metastases following stereotactic body radiotherapy versus three-dimensional conformal radiotherapy.

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.

Challenges of a HL7 CDA Guideline for Telehealth Based DMP Systems.

BACKGROUND: Disease management programs (DMP) are a modern way of treating health conditions and are becoming a part of standard care. One telehealth DMP service has been in regular operation since 2017, named "HerzMobil Tirol". OBJECTIVES: This paper investigates, if the electronic health record standard HL7 CDA, which is widely accepted in the health care industry, could be used for telehealth DMP services as well. It is already in use in a legally required integrated element of healthcare in Austria called ELGA. An official guideline from the Austrian Ministry of Health sets the standard for telemonitoring with data logging. METHODS: After the background knowledge was built up, requirements have been gathered through existing official guidelines and interviews and existing documentation by "HerzMobil Tirol". RESULTS: Twenty-five requirements were collected, categorized and analyzed to determine if the existing CDA guidelines are suitable or a new standard must be designed. CONCLUSION: Based on the requirements, it was established that seven specific sections and two different CDA documents are needed.

Intensity-modulated radiotherapy with integrated-boost in patients with bone metastasis of the spine: study protocol for a randomized controlled trial.

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.

HerzMobil, an Integrated and Collaborative Telemonitoring-Based Disease Management Program for Patients With Heart Failure: A Feasibility Study Paving the Way to Routine Care.

BACKGROUND: Heart failure is a major health problem associated with frequent hospital admissions. HerzMobil Tirol is a multidisciplinary postdischarge disease management program for heart failure patients to improve quality of life, prevent readmission, and reduce mortality and health care costs. It uses a telemonitoring system that is incorporated into a network of specialized heart failure nurses, physicians, and hospitals. Patients are equipped with a mobile phone, a weighing scale, and a blood pressure and heart rate monitor for daily acquisition and transmission of data on blood pressure, heart rate, weight, well-being, and drug intake. These data are transmitted daily and regularly reviewed by the network team. In addition, patients are scheduled for 3 visits with the network physician and 2 visits with the heart failure nurse within 3 months after hospitalization for acute heart failure. OBJECTIVE: The objectives of this study were to evaluate the feasibility of HerzMobil Tirol by analyzing changes in health status as well as patients' self-care behavior and satisfaction and to derive recommendations for implementing a telemonitoring-based interdisciplinary disease management program for heart failure in everyday clinical practice. METHODS: In this prospective, pilot, single-arm study including 35 elderly patients, the feasibility of HerzMobil Tirol was assessed by analyzing changes in health status (via Kansas City Cardiomyopathy Questionnaire, KCCQ), patients' self-care behavior (via European Heart Failure Self-Care Behavior Scale, revised into a 9-item scale, EHFScB-9), and user satisfaction (via Delone and McLean System Success Model). RESULTS: A total of 43 patients joined the HerzMobil Tirol program, and of these, 35 patients completed it. The mean age of participants was 67 years (range: 43-86 years). Health status (KCCQ, range: 0-100) improved from 46.2 to 69.8 after 3 months. Self-care behavior (EHFScB-9, possible range: 9-22) after 3 months was 13.2. Patient satisfaction in all dimensions was 86% or higher. Lessons learned for the rollout of HerzMobil Tirol comprise a definite time schedule for interventions, solid network structures with clear process definition, a network coordinator, and specially trained heart failure nurses. CONCLUSIONS: On the basis of the positive evaluation results, HerzMobil Tirol has been officially introduced in the province of Tyrol in July 2017. It is, therefore, the first regular financed telehealth care program in Austria.

Stability of Spinal Bone Lesions in Patients With Multiple Myeloma After Radiotherapy-A Retrospective Analysis of 130 Cases.

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.

Spinal bone metastases in colorectal cancer: a retrospective analysis of stability, prognostic factors and survival after palliative radiotherapy.

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%.

Differentiated resistance training of the paravertebral muscles in patients with unstable spinal bone metastasis under concomitant radiotherapy: study protocol for a randomized pilot trial.

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.