Stability and survival analysis of elderly patients with osteolytic spinal bone metastases after palliative radiotherapy : Results from a large multicenter cohort.

PURPOSE: This retrospective study aimed to evaluate the stability and fracture rates of osteolytic spinal bone metastases (SBM) in elderly patients following palliative radiotherapy (RT) and to derive prognostic factors for stability and survival. METHODS: A total of 322 patients aged at least 70 years received palliative RT at two major German academic medical centers or at the German Cancer Research Center. Stability assessment was based on the validated Taneichi score prior to RT and at 3 and 6 months after RT. The survival time following RT was assessed, and prognostic factors for stability and survival were analyzed. RESULTS: Prior to RT, 183 patients (57%) exhibited unstable SBM and 68 patients (21%) pathological fractures. At 3 and 6 months after RT, significant recalcification and stabilization were evident in 19% (23/118) and 40% (31/78) of surviving patients, respectively. Only 17 patients (5%) experienced new pathological fractures following RT. Tumor histology was found to significantly influence stabilization rates with only breast cancer patients exhibiting increased stabilization compared to patients with other histologies. The median survival time and 6­month survival rates following RT were 5.4 months (95% confidence interval 4.4-7.2 months) and 48%, respectively. The patients' performance status was found to be the strongest predictor for survival after RT in this patient cohort; further factors demonstrating a significant association with survival were the application of systemic treatment, the number of SBM and the primary tumor histology. To analyze the influence of age on survival after RT, study patients were stratified into 3 age groups (i.e., 70-74 years, 75-79 years, and ≥80 years). The subgroup of patients aged at least 80 years showed a strong trend towards a worse survival time following RT compared to younger patients (i.e., 6­month survival rate 39% vs. 51%; p = 0.06, log-rank test). CONCLUSIONS: Prognostic factors influencing overall survival such as performance status and histology should guide the choice for palliative RT for SBM. Strongly hypofractionated RT regimes may be advisable for most elderly patients considering the overall poor prognosis in order to reduce hospitalization times.

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.

Local response and pathologic fractures following stereotactic body radiotherapy versus three-dimensional conformal radiotherapy for spinal metastases - a randomized controlled trial.

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.

Survival and Stability of Patients with Urothelial Cancer and Spinal Bone Metastases after Palliative Radiotherapy.

BACKGROUND: The aim of the study was to analyze survival and stability of patients with urothelial cell cancer and spinal bone metastases (SBM) after radiotherapy (RT). Furthermore, to assess the effects of RT on bone mineral density (BMD) as a local response in SBM after RT. PATIENTS AND METHODS: Survival of 38 patients with 132 SBM from urothelial cancer, treated from January 2000 to January 2012, was calculated. Stability of irradiated thoracic and lumbar SBM was retrospectively evaluated in computed tomography (CT) scans using the validated Taneichi et al. score. Difference in BMD, measured in Hounsfield units (HU), of the SBM before and at 3 and 6 months after RT was analyzed. RESULTS: All patients died during follow-up. Overall survival (OS) after 6 months, 1 year and 2 years was 90%, 80% and 40%, respectively. Bone survival (BS) was 85%, 64% and 23% after 6 months, 1 year and 2 years, respectively. Survival from start of RT (RTS) was 42% after 6 months, 18% after 1 year and 5% after 2 years. Only 11% received bisphosphonates. Stability did not improve at 3 or 6 months after RT. BMD increased by 25.0 HU ± 49.7 SD after 3 months (p = 0.001) and by 24.2 HU ± 52.2 SD after 6 months (p = 0.037). Pain relief (> 2 points on the visual analogue scale) was achieved in only 27% of patients. CONCLUSIONS: Benefit from palliative RT of painful or unstable SBM is limited in these patients and they should be carefully selected for RT. Shorter fractionation schedules may be preferred and outcome may improve with concomitant bisphosphonates.

Prognostic factors for long-term quality of life after adjuvant radiotherapy in women with endometrial cancer.

BACKGROUND: Adjuvant radiotherapy (RT) for endometrial cancer (EC) may affect patients' quality of life (QoL). There is a paucity of data on prognostic factors for long-term QoL and sexual functioning. This study aimed to investigate such factors and assess the role of the vaginal dilator (VD). METHODS: QoL was assessed in 112 EC patients 6 years (median) after RT. QoL was compared to normative data, and the influence of age, tumor characteristics, lymphadenectomy, RT, and acute toxicities was assessed. VD use and its effect on subjective vaginal shortening/tightness was analyzed. RESULTS: QoL was reduced, particularly in younger patients. Vaginal brachytherapy only and intensity-modulated RT (IMRT) were associated with better global health status and reduced chronic gastrointestinal (GI) symptoms. Higher acute GI toxicity was associated with increased chronic GI symptoms, particularly diarrhea, and reduced role functioning. Higher acute urinary toxicity was associated with increased chronic urological symptoms, muscular/pelvic pain, and chronic GI symptoms, as well as with reduced emotional/social functioning and reduced global health status. Sexual interest/activity was increased despite vaginal dryness and dyspareunia. Sexual interest/activity increased with age. Only few, mainly younger patients used the VD. VD use >1 year was found in women with higher sexual interest/activity. Acute vaginal toxicity and chronic pain prevented VD use. Subjective vaginal shortening/tightness was not reduced in VD users. CONCLUSION: RT technique and acute toxicities are prognostic for the extent of chronic symptoms and long-term QoL. Sexuality is important even at a higher age. Few patients use the VD and a reduction of subjective vaginal shortening/tightness was not achieved.

Survival and prognostic factors in patients with stable and unstable spinal bone metastases from solid tumors: a retrospective analysis of 915 cases.

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.

Biochemical markers of bone turnover in patients with spinal metastases after resistance training under radiotherapy--a randomized trial.

BACKGROUND: To compare the effects of resistance training versus passive physical therapy on bone turnover markers (BTM) in the metastatic bone during radiation therapy (RT) in patients with spinal bone metastases. Secondly, to evaluate an association of BTM to local response, skeletal-related events (SRE), and number of metastases. METHODS: In this randomized trial, 60 patients were allocated from September 2011 to March 2013 into one of the two arms: resistance training (Arm A) or passive physical therapy (Arm B) with thirty patients in each arm during RT. Biochemical markers such as pyridinoline (PYD), desoxy-pyridinoline (DPD), bone alkaline phosphatase (BAP), total amino-terminal propeptide of type I collagen (PINP), beta-isomer of carboxy-terminal telopeptide of type I collagen (CTX-I), and cross-linked N-telopeptide of type I collagen (NTX) were analyzed at baseline, and three months after RT. RESULTS: Mean change values of PYD and CTX-I were significantly lower at 3 months after RT (p = 0.035 and p = 0.043) in Arm A. Importantly, all markers decreased in both arms, except of PYD and CTX-I in arm B, although significance was not reached for some biomarkers. In arm A, the local response was significantly higher (p = 0.003) and PINP could be identified as a predictor for survivors (OR 0.968, 95%CI 0.938-0.999, p = 0.043). BAP (OR 0.974, 95%CI 0.950-0.998, p = 0.034) and PINP (OR 1.025, 95%CI 1.001-1.049, p = 0.044) were related with an avoidance of SRE. CONCLUSIONS: In this group of patients with spinal bone metastases, we were able to show that patients with guided resistance training of the paravertebral muscles can influence BTM. PYD and CTX-I decreased significantly in arm A. PINP can be considered as a complementary tool for prediction of local response, and PINP as well as BAP for avoidance of SRE. TRIAL REGISTRATION: Clinical trial identifier NCT 01409720. August 2, 2011.

The influence of orthopedic corsets on the incidence of pathological fractures in patients with spinal bone metastases after radiotherapy.

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.

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 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.

Stability of spinal bone metastases in breast cancer after radiotherapy: a retrospective analysis of 157 cases.

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.

Trimodal therapy for stage III-N2 non-small-cell lung carcinoma: a single center retrospective analysis.

BACKGROUND: Treatment of locally advanced non-small-cell lung cancer is based on a combined approach. To study the impact of trimodal therapy for stage III-N2 NSCLC a single centre retrospective evaluation focusing on survival and therapy-related toxicity was performed. METHODS: 71 patients diagnosed between March 2001 and August 2008 with pathologically confirmed stage III-N2 non-small-cell lung cancer at the University Clinic of Heidelberg were retrospectively analyzed. All patients were treated within trimodal therapy strategies including surgery, induction or adjuvant chemotherapy and postoperative radiotherapy. Overall survival (OS) and disease free survival (DFS) rates were calculated using the Kaplan-Meier method. The log-rank test and Fishers Exact test were applied for univariate analysis and Cox proportional regression model for multivariate analysis. RESULTS: Median survival was 32 months. 1-, 3- and 5-year overall survival (OS) rates were 84.5%, 49.6% and 35.5% respectively. Disease free survival rates at 1, 3 and 5 years were 70.4%, 41.8% and 27.4% respectively. 9 patients (12.6%) were diagnosed with a local recurrence. Multivariate analysis did not reveal any independent prognostic factors for OS, but indicated a trend for pT stage and type of surgery. In regard to toxicity 8.4% of the patients developed a clinically relevant ≥ grade 2 pneumonitis. Evaluation of the forced expiratory volume in 1 second per unit of vital capacity (FEV1/VC) before and 1-3 years post radiotherapy revealed a median decrease of 2.1%. CONCLUSIONS: Our descriptive data indicate that trimodal therapy represents an effective and safe treatment approach for patients with stage III-N2 non-small-cell lung cancer. Further prospective clinical trials are necessary in order to clearly define the impact of multimodal strategies and optimize NSCLC treatment.

Pain response of resistance training of the paravertebral musculature under radiotherapy in patients with spinal bone metastases--a randomized trial.

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.

Feasibility of isometric spinal muscle training in patients with bone metastases under radiation therapy - first results of a randomized pilot trial.

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.

Isometric muscle training of the spine musculature in patients with spinal bony metastases under radiation therapy.

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.

Spinal Stabilization Exercises for Cancer Patients with Spinal Metastases of High Fracture Risk: Feasibility of the DISPO-II Training Program.

Exercise concomitant to radiotherapy for stable spinal metastases was demonstrated to increase bone density and reduce pain. In the DISPO-II study, the feasibility of exercise concomitant to radiotherapy for unstable spinal metastases was investigated. Here, a detailed analysis of the training program is presented. Cancer patients with spinal metastases (Taneichi score ≥ D) were randomly assigned to an intervention group (INT, n = 27, 62 ± 9 years) or control group (CON, n = 29, 61 ± 9 years). INT performed spinal stabilization exercises ("all fours"/"plank"/"swimmer"/"band exercise"), and CON received relaxation, daily concomitant to radiotherapy. Exercise attendance rate was 90% in INT and 80% in CON (p = 0.126). Within INT, exercise dose increased significantly (p < 0.001). 54% of patients could not perform "swimmer" in some or all sessions. 42% could not perform "plank" in some or all sessions. 13 and 25% could not perform "all fours" and "band exercise" in some sessions. "Plank" holding time increased in INT and remained unchanged in CON with different development between groups (p = 0.022). Handgrip strength did not develop differently between groups (p = 0.397). The exercise intervention demonstrated high acceptability but required frequent modifications due to pain, weakness and immobility to be feasible for the majority of participants. It enhanced specific muscle strength. Larger trials should now investigate exercise effects on health.

Comparative Analyses of Two Established Scores to Assess the Stability of Spinal Bone Metastases Before and After Palliative Radiotherapy.

BACKGROUND AND PURPOSE: To compare two validated spinal instability scores regarding the stabilizing effects and skeletal-related events (SREs) of palliative radiotherapy (RT) in patients with spinal bone metastases (SBM). MATERIALS AND METHODS: Two hundred eighty-two osteolytic SBM of lung or breast cancer patients were analyzed for stability before and following RT based on the Spinal Instability Neoplastic Score (SINS) or the Taneichi score. Score concordance was quantified by absolute agreement and Cohen's kappa coefficient. SREs were defined as fractures or local progression after RT. OS was quantified as the time between the start of RT and death from any cause. RESULTS: At 3 and 6 months after RT, 35 and 50% of initially unstable SBM were re-stabilized according to SINS in patients still alive. Corresponding Taneichi score-based stabilization proportions were 25 and 46%, respectively. Comparison of both stability scores showed high absolute agreement for all time-points (range 71-78%, kappa range 0.35-0.44). SRE occurred more frequently in initially unstable SBM compared to stable SBM according to SINS (14 vs. 5%), but no such association could be shown for the Taneichi-based instability criterion. Poor general condition of patients was negatively associated with SINS-measured re-stabilization after 6 months, but no predictive factor for re-stabilization could be found for the Taneichi score. CONCLUSIONS: Despite the relatively high agreement between both stabilization scores, the SINS should be considered the standard for future studies on the stabilization effects of RT in SBM.

The Role of Palliative Radiotherapy in the Treatment of Spinal Bone Metastases from Head and Neck Tumors-A Multicenter Analysis of a Rare Event.

This retrospective multi-center analysis aimed to assess the clinical response and stabilizing effects of palliative radiotherapy (RT) for spinal bone metastases (SBM) in head and neck cancer (HNC), and to establish potential predictive factors for stability and overall survival (OS). Patients included in this analysis were treated at the University Hospitals of Mainz, Freiburg, and Heidelberg between 2001 and 2019. Clinical information was taken from the medical records. The stability of affected vertebral bodies was assessed according to the validated spine instability neoplastic score (SINS) based on CT-imaging before RT, as well as 3 and 6 months after RT. OS was quantified as the time between the start of palliative RT and death from any cause or last follow-up. Potential predictive factors for stability and OS were analyzed using generalized estimating equations and Cox regression for time-varying covariates to take into account multiple observations per patient. The mean follow-up time of 66 included patients after the first palliative RT was 8.1 months (range 0.3-85.0 months). The majority of patients (70%; n = 46) had squamous cell carcinomas (SCC) originating from the pharynx, larynx and oral cavity, while most of the remaining patients (26%; n = 17) suffered from salivary glands tumors. A total of 95 target volumes including 178 SBM were evaluated that received a total of 81 irradiation series. In patients with more than one metastasis per irradiated region, only the most critical bone metastasis was analyzed according to the SINS system. Prior to RT, pain and neurologic deficits were present in 76% (n = 72) and 22% (n = 21) of irradiated lesions, respectively, and 68% of the irradiated lesions (n = 65) were assessed as unstable or potentially unstable prior to RT. SBM-related pain symptoms and neurologic deficits responded to RT in 63% and 47% of the treated lesions, respectively. Among patients still alive at 3 and 6 months after RT with potentially unstable or unstable SBM, a shift to a better stability class according to the SINS was observed in 20% and 33% of the irradiated SBM, respectively. Pathological fractures of SBM were frequently detected before the start of irradiation (43%; n = 41), but after RT, new fractures or increasing vertebral body sintering within the irradiated region occurred rarely (8%; n = 8). A pathological fracture before RT was negatively associated with stabilization 6 months after RT (OR 0.1, 95% CI 0.02-0.49, p = 0.004), while a Karnofsky performance score (KPS) ≥ 70% was associated positively with a stabilization effect through irradiation (OR 6.09, 95% CI 1.68-22.05, p = 0.006). Mean OS following first palliative RT was 10.7 months, and the KPS (≥70% vs. <70%) was shown to be a strong predictive factor for OS after RT (HR 0.197, 95% CI 0.11-0.35, p < 0.001). There was no significant difference in OS between patients with SCC and non-SCC. Palliative RT in symptomatic SBM of HNC provides sufficient symptom relief in the majority of patients, while only about one third of initially unstable SBM show re-stabilization after RT. Since patients in our multi-center cohort exhibited very limited OS, fractionation schemes should be determined depending on the patients' performance status.

Paravertebral Muscle Training in Patients with Unstable Spinal Metastases Receiving Palliative Radiotherapy: An Exploratory Randomized Feasibility Trial.

Background: Isometric paravertebral muscle training (IPMT) may improve mobility, pain, and quality of life (QOL) in cancer patients with spinal metastases. However, this regimen remains unproven in patients with unstable spinal metastases (USM), a population at high risk for clinical exacerbation with such interventions. Thus, we conducted this exploratory, non-blinded, randomized controlled trial (NCT02847754) to evaluate the safety/feasibility of IPMT and secondarily assess pain, bone density, pathologic fracture rate, and QOL. Methods: All patients had histologically/radiologically confirmed USM (per Taneichi score) and underwent non-operative management with 5-10 fractions of palliative radiotherapy (RT). Randomization (1:1) groups were IPMT (intervention, INT) or muscle relaxation (control, CON); both lasted 15 min/day and started concurrently with radiotherapy. The primary endpoint was feasibility (completion of training programs three months post-RT). Secondary endpoints were pain response (Visual Analog Scale) and opioid consumption, bone density and pathologic fracture rate, and QOL (European Organization for Research and Treatment of Cancer, EORTC questionnaires). Results: Sixty patients were randomized and 56 received protocol therapy. Mean survival in both groups was 4.4 months. There were no adverse events with either training regimen. Altogether, ≥80% of the planned sessions were completed by 55% (n = 16/29) in CON and 67% (n = 18/27) in INT. Regarding the post-radiotherapy home-based training, ≥80% of planned sessions were completed by 64% (n = 9/14) of the INT cohort. There were no differences in pain scores, opioid consumption, or bone density between arms (p > 0.05 for all). No difference was observed between groups regarding new pathological fractures (INT: n = 1 vs. CON: n = 3) after three months (p = 0.419). There were no QOL differences between arms (all parameters p > 0.05). Conclusions: IPMT is potentially feasible for high-risk USM patients. Future trials adequately powered for relevant endpoints are thus recommended.

Percutaneous parametrial dose escalation in women with advanced cervical cancer: feasibility and efficacy in relation to long-term quality of life.

Background We analyzed long-term quality of life (QoL) and prognostic factors for QoL as well as clinical outcome in patients with advanced cervical cancer (ACC) treated with primary radiochemotherapy (RChT) consisting of external beam radiotherapy (EBRT) with or without sequential or simultaneous integrated boost (SIB) to the parametria, intracavitary brachytherapy and concomitant chemotherapy (ChT). Patients and methods Eighty-three women were treated with primary RChT between 2008 and 2014. Survival of all patients was calculated and prognostic factors for survival were assessed in univariate and multivariate analysis. In 31 patients QoL was assessed in median 3 years (range 2-8 years) after treatment. QoL was compared to published normative data and the influence of age, tumour stage, treatment and observed acute toxicities was analyzed. Results Thirty-six patients (43.4%) died, 18 (21.7%) had a local recurrence and 24 (28.9%) had a distant progression. Parametrial boost (p = 0.027) and ChT (p = 0.041) were independent prognostic factors for overall survival in multivariate analysis. Specifically, a parametrial equivalent doses in 2-Gy fractions (EQD2) > 50 Gy was associated with an improved overall survival (OS) (p = 0.020), but an EQD2 > 53 Gy did not further improve OS (p = 0.194). Tumour size was the only independent prognostic factor for local control (p = 0.034). Lymph node status (p = 0.038) and distant metastases other than in paraaortic lymph nodes (p = 0.002) were independent prognostic factors for distant progressionfree survival. QoL was generally inferior to the reference population. Age only correlated with menopausal symptoms (p = 0.003). The degree of acute gastrointestinal (p = 0.038) and genitourinary (p = 0.041) toxicities correlated with the extent of chronic symptom experience. Sexual/vaginal functioning was reduced in patients with larger tumours (p = 0.012). Parametrial EQD2 > 53 Gy correlated with reduced sexual/vaginal functioning (p = 0.009) and increased sexual worry (p = 0.009). Whether parametrial dose escalation was achieved by sequential boost or SIB, did not affect survival or QoL. Conclusions Primary RChT is an effective treatment, but long-term QoL is reduced. The degree of acute side effects of RChT correlates with the extent of chronic symptoms. Patients benefit from parametrial SIB or sequential boost, but an EQD2 > 53 Gy does not further improve survival and negatively affects QoL.

Bone density and pain response following intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for vertebral metastases - secondary results of a randomized trial.

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.