Robert Förster

The effect of resistance training during radiotherapy on spinal bone metastases in cancer patients – A randomized trial

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.

High-dose single-fraction IMRT versus fractionated external beam radiotherapy for patients with spinal bone metastases: study protocol for a randomized controlled trial

BackgroundStereotactic 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/designThis 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.DiscussionThe 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 registrationClinicalTrials.gov identifier NCT02358720 (June 2, 2015).

Stability of spinal bone metastases and survival analysis in renal cancer after radiotherapy.

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.

Stability, prognostic factors and survival of spinal bone metastases in malignant melanoma patients after palliative radiotherapy

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) <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 <70%, visceral metastases and multiple bone metastases. Given the limited life expectancy, short fractionated treatment schedules of RT may be preferred in this population.

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

Micro‐Abstract This retrospective analysis evaluated the response regarding bone density and stability of patients with osteolytic spinal bone lesions due to multiple myeloma after palliative radiotherapy. The rate of unstable lesions decreased from 51% to 24%, and the bone density showed a significant increase 6 months after radiotherapy. Palliative radiotherapy is an effective method resulting in a significant increase for local response and stability without severe RT‐related toxicity. 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 &kgr; 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.

Intensity-modulated radiotherapy versus proton radiotherapy versus carbon ion radiotherapy for spinal bone metastases: a treatment planning study

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 5 Gy (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. PACS number: 87.55.dkOutcomes 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 5 Gy (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. PACS number: 87.55.dk.

Radiation-induced toxicity after image-guided and intensity-modulated radiotherapy versus external beam radiotherapy for patients with spinal bone metastases (IRON-1): a study protocol for a randomized controlled pilot trial

BackgroundRadiation 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/designIn 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.DiscussionThe 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 registrationClinicalTrials.gov, NCT02832830. Registered on 12 July 2016.

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

BackgroundMetastatic 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/DesignThis 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.DiscussionDespite 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 registrationClinicalTrials.gov, identifier: NCT02847754. Registered on 27 July 2016.

Adjuvante IMRT beim Endometriumkarzinom

benutzen. Die Dosis des vaginalen und nodalen Planungszielvolumen betrug 45 Gy in 25 Fraktionen. Um die Compliance mit den Protokollleitlinien der einzelnen Zentren zu bestimmen, wurden diese gebeten, eine Testprozedur vor dem Einschluss der ersten Patientin durchzuführen. GIund urogenitale (GU) Toxizitäten wurden nach CTCAE v3.0 klassifiziert und während der Bestrahlung prospektiv wöchentlich sowie zu den Brachytherapiesitzungen und bei der Nachsorgeuntersuchung in Woche 15 erfasst. Besondere Aufmerksamkeit galt Veränderungen jeglichen Grads der Nebenwirkungen zwischen Woche 5 und 15.

Quality of Life Following Stereotactic Body RadiotherapyVersusThree-Dimensional Conformal Radiotherapy for Vertebral Metastases: Secondary Analysis of an Exploratory Phase II Randomized Trial

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.