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Secondary Bone Cancer (bone metastasis)

Secondary bone cancer is where malignant cells have spread to the bones from other parts of the body. This is different to cancer that actually started in the bones (primary bone cancer). Virtually all types of cancer can spread to bone. Bone metastases are particularly common in people with breast, lung or prostate cancer. Bone metastases are usually multiple, they cause pain and can can lead to other symptoms such as hypercalcemia (abnormally high levels of calcium in the blood).

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    MeSH term: Bone Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Yassaad OM, Nabil R, KacemiInas E, et al.
Primary multiple osseous leiomyosarcomas of the spine metastasizing to the skull.
Pan Afr Med J. 2016; 24:334 [PubMed] Free Access to Full Article Related Publications
Primary osseous leiomyosarcoma of the spine is a very unusual condition, with only few cases being reported in the literature. In fact, this type of tumors arises from the smooth muscle cells and occurs usually in the uterus and the gastrointestinal tracts. If the spine should be involved, it occurs generally as a metastatic location. Location to the spine as a primary site is exceedingly rare. We present the case of a 37 years old female patient, with multiple spine levels involvement - to vertebral body and to posterior aspects of Vertebra, causing spinal cord compression syndrome. A secondary location to the skull was diagnosed one month later. Through a literature review, we analyze various aspects in the diagnosis and management of this rare entity.

Irawan C, Atmakusumah D, Siregar NC, et al.
Expression of Biomarkers CXCR4, IL11-RA, TFF1, MLF1P in Advanced Breast Cancer Patients with Bone Metastatic: a Diagnostic Study.
Acta Med Indones. 2016; 48(4):261-268 [PubMed] Related Publications
AIM: to analyze expression of biomarkers CXCR4, IL11-RA, TFF1 and MLF1P, and clinicopathology in advanced breast cancer patients with bone metastatic.
METHODS: this is a cross-sectional study. Analysis was done against a total of 92 breast cancer patients, including 46 bone metastatic patients and 46 non-bone metastatic patients. Immunohistochemistry and microarray analysis was performed in 81 formalin fixed paraffin embedded (FFPE) samples from 81 patients were used. Data were collected through medical records, immunohistochemistry (IHC), and microarray with nanoString nCounterTM.
RESULTS: this article is part one of a two stage reporting research results. In part one we got the results of the IHC analysis, IL11-RA with cut-off ≥103.5 showed OR 3.803 (95 % confidence interval [CI], 1.375-10.581), p=0.010, MLF1P with cut-off ≥83.0 OR 2.784 (95% CI, 1.009-7.681), p=0.048, and ER+ OR 7.640 (95 % CI, 2.599-22.459), p<0.000, were associated with bone metastastic incidences in advanced breast cancer, and were statistically significantly different. A combination of IL-11RA, MLF1P and ER+, showed an accuracy of approaching 80% to discriminate between bone metastatic and non bone metastatic in advanced breast cancer patients.
CONCLUSION: IL11-RA, MLF1P, and ER+ were the determinants that were associated with increasing bone metastasis incidence.

Yao L, Cao Q, Wang J, et al.
CT-Guided (125)I Seed Interstitial Brachytherapy as a Salvage Treatment for Recurrent Spinal Metastases after External Beam Radiotherapy.
Biomed Res Int. 2016; 2016:8265907 [PubMed] Free Access to Full Article Related Publications
The aim of this study is to evaluate the feasibility, safety, and clinical efficacy of CT-guided (125)I seed interstitial brachytherapy in patients with recurrent spinal metastases after external beam radiotherapy (EBRT). Between August 2003 and September 2015, 26 spinal metastatic lesions (24 patients) were reirradiated by this salvage therapy modality. Treatment for all patients was preplanned using a three-dimensional treatment planning system 3-5 days before (125)I seed interstitial brachytherapy; dosimetry verification was performed immediately after seed implantation. Median actual D90 was 99 Gy (range, 90-176), and spinal cord median Dmax was 39 Gy (range, 6-110). Median local control (LC) was 12 months (95% CI: 7.0-17.0). The 6- and 12-month LC rates were 52% and 40%, respectively. Median overall survival (OS) was 11 months (95% CI: 7.7-14.3); 6-month and 1-, 2-, and 3-year OS rates were 65%, 37%, 14%, and 9%, respectively. Pain-free survival ranged from 2 to 42 months (median, 6; 95% CI: 4.6-7.4). Treatment was well-tolerated, with no radiation-induced vertebral compression fractures or myelopathy reported. Reirradiation with CT-guided (125)I seed interstitial brachytherapy appears to be feasible, safe, and effective as pain relief or salvage treatment for patients with recurrent spinal metastases after EBRT.

Zheng G, Li H, Li J, et al.
Metastatic renal clear cell carcinoma to the rectum, lungs, ilium, and lymph nodes: A case report.
Medicine (Baltimore). 2017; 96(1):e5720 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Renal cell carcinoma metastasizing to rectum is very rare, and the unusual metastatic sites should be paid attention to during the follow-up of renal cell carcinoma.
CASE SUMMARY: We describe a case of a 65-year-old male who was diagnosed with metastatic renal cell carcinoma to rectum 10 years after the right radical nephrectomy. Histopathology and immunohistochemical examinations contribute to making differential diagnosis between rectal metastasis of renal cell carcinoma and primary rectal clear cell carcinoma. Positron emission tomography-computed tomography with fluorodeoxyglucose shows hypermetabolic activity in upper rectum and other sites of metastasis at the same time.
CONCLUSION: Possibility of unusual metastatic sites of renal cell carcinoma such as rectum indeed exists, which should not be ignored in the surveillance after resection of the primary tumor.

de Ruiter GC, Nogarede CO, Wolfs JF, Arts MP
Quality of life after different surgical procedures for the treatment of spinal metastases: results of a single-center prospective case series.
Neurosurg Focus. 2017; 42(1):E17 [PubMed] Related Publications
OBJECTIVE The performance of surgery for spinal metastases is rapidly increasing. Different surgical procedures, ranging from stabilization alone to stabilization combined with corpectomy, are thereby performed for various indications. Little is known about the impact of these different procedures on patient quality of life (QOL), but this factor is crucial when discussing the various therapeutic options with patients and their families. Thus, the authors of this study investigated the effect of various surgical procedures for spinal metastases on patient QOL. METHODS The authors prospectively followed a cohort of 113 patients with spinal metastases who were referred to their clinic for surgical evaluation between July 2012 and July 2014. Quality of life was assessed using the EQ-5D at intake and at 3, 6, 9, and 12 months after treatment. RESULTS Nineteen patients were treated conservatively, 41 underwent decompressive surgery with or without stabilization, 47 underwent a piecemeal corpectomy procedure with stabilization and expandable cage reconstruction, and 6 had a stabilization procedure without decompression. Among all surgical patients, the mean EQ-5D score was significantly increased from 0.44 pretreatment to 0.59 at 3 months after treatment (p < 0.001). Mean EQ-5D scores at 1 year after surgery further increased to 0.84 following decompression with stabilization, 0.74 after corpectomy with stabilization, and 0.94 after stabilization without decompression. Frankel scores also improved after surgery. There were no significant differences in improvements in EQ-5D scores and Frankel grades among the different surgical procedures. In addition, mortality and complication rates were similar. CONCLUSIONS Quality of life can improve significantly after various extensive and less extensive surgical procedures in patients with spinal metastases. The relatively invasive corpectomy procedure, as compared with alternative less invasive techniques, does not negatively affect outcome.

Himelstein AL, Foster JC, Khatcheressian JL, et al.
Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial.
JAMA. 2017; 317(1):48-58 [PubMed] Article available free on PMC after 03/07/2017 Related Publications
Importance: Zoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain.
Objective: To determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks.
Design, Setting, Participants: Randomized, open-label clinical trial conducted at 269 academic and community sites in the United States. Patients (n = 1822) with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement were enrolled between May 2009 and April 2012; follow-up concluded in April 2014.
Interventions: Patients were randomized to receive zoledronic acid administered intravenously every 4 weeks (n = 911) vs every 12 weeks (n = 911) for 2 years.
Main Outcomes and Measures: The primary end point was the proportion of patients having at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years after randomization and a between-group absolute difference of 7% as the noninferiority margin. Secondary end points included the proportion of patients with at least 1 skeletal-related event by disease type, pain as assessed by the Brief Pain Inventory (range, 0-10; higher scores indicate worse pain), Eastern Cooperative Oncology Group performance status (range, 0-4; higher scores indicate worse disability), incidence of osteonecrosis of the jaw, kidney dysfunction, skeletal morbidity rate (mean number of skeletal-related events per year), and, in a subset of 553 patients, suppression of bone turnover (assessed by C-terminal telopeptide levels).
Results: Among 1822 patients who were randomized (median age, 65 years; 980 [53.8%] women; 855 with breast cancer, 689 with prostate cancer, and 278 with multiple myeloma), 795 completed the study at 2 years. A total of 260 patients (29.5%) in the zoledronic acid every 4-week dosing group and 253 patients (28.6%) in the every 12-week dosing group experienced at least 1 skeletal-related event within 2 years of randomization (risk difference of -0.3% [1-sided 95% CI, -4% to ∞]; P < .001 for noninferiority). The proportions of skeletal-related events did not differ significantly between the every 4-week dosing group vs the every 12-week dosing group for patients with breast cancer, prostate cancer, or multiple myeloma. Pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the treatment groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks.
Conclusions and Relevance: Among patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, the use of zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 weeks did not result in an increased risk of skeletal events over 2 years. This longer interval may be an acceptable treatment option.
Trial Registration: clinicaltrials.gov Identifier: NCT00869206.

Atkinson RA, Jones A, Ousey K, Stephenson J
Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis.
J Hosp Infect. 2017; 95(2):148-153 [PubMed] Related Publications
BACKGROUND: Surgical site infection (SSI) is a serious potential complication of spinal surgery. SSI may impact significantly on inpatient hospitalization and the costs associated with extra care.
AIM: To investigate the management of patients experiencing SSI following surgery for spinal metastatic tumours, and to estimate the costs associated with SSI in this context.
METHODS: Patients experiencing SSI following spinal tumour surgery at a large spinal surgery centre between January 2009 and December 2012 were identified. Existing case notes were reviewed and patient and procedural data, details of the infection, and treatment interventions were recorded. A bottom-up approach to calculating costs associated with infection was used for patients experiencing SSI and compared with a quasi-random sample of similar patients without SSI.
FINDINGS: The mean cost of treating patients with SSI was significantly greater than costs associated with those without SSI (P=0.019). Mean cost of inpatient hospital stay was 60% higher in patients with SSI compared to those without SSI (P=0.004). Inpatient hospital stay alone accounted for 59% of total costs. Return to theatre was the second most costly intervention overall, accounting for 38% of costs, and was the most expensive single intervention involved in the treatment of SSI.
CONCLUSION: SSI significantly increases healthcare costs for patients undergoing surgery for spinal metastasis, with prolonged inpatient hospitalization and return to theatre for wound management being major contributors. The actual total cost to society derived from SSI in this patient group is likely to be far beyond just the direct costs to healthcare providers.

An H, Tao N, Li J, et al.
Detection of Prostate Cancer Metastasis by Whole Body Magnetic Resonance Imaging Combined with Bone Scintigraphy and PSA Levels.
Cell Physiol Biochem. 2016; 40(5):1052-1062 [PubMed] Related Publications
BACKGROUND/AIMS: The combined role of whole-body magnetic resonance imaging (WB-MRI), bone scintigraphy and prostate specific antigen (PSA) were considered in predicting metastases and prognosis of prostate cancer (PCa).
METHODS: Totally 38 PCa patients underwent WB-MRI, bone scintigraphy and PSA detections, and 34 benign prostate hyperplasia (BPH) patients were checked with PSA. Pearson correlations were performed to determine associations among PSA, apparent diffusion coefficient (ADC) and Gleason scoring. Specificity and sensitivity were for comparison of diagnostic accuracies. Patients' baseline PSA, PSA nadir and time to the prostate-specific antigen nadir (TTPN) were analyzed, and Kaplan-Meier survival curves were also established.
RESULTS: ADC values were negatively correlated with PSA levels (rs = -0.389, P = 0.016) and Gleason scores (rs = -0.432, P = 0.006), while PSA levels were positively correlated with Gleason scoring (rs = 0.493, P = 0.002). Diagnostic efficacy of whole body-diffusion weighted imaging (WB-DWI) combined with PSA seemed the most favorable, and bone scintigraphy was advantageous in identifying bone metastasis. PSA levels (> 61.60 µg/L), Gleason scores (> 6) and ADC (< 0.81 × 10-3 mm2/s) could all predict pessimistic prognosis (HR = 7.65; HR = 6.09; HR = 7.28). Smaller PSA nadir (≤ 1.0 µg/L) and longer TTPN (> 3 months) were associated with increased 5-year survival rate (P < 0.05).
CONCLUSIONS: The combined efficacies of WB-MRI, bone scintigraphy and PSA levels were desired in identifying PCa lesions and prognosis.

Thellenberg-Karlsson C, Nyman C, Nilsson S, et al.
Bone-targeted Novel Cytotoxic Polybisphosphonate Conjugate in Castration-resistant Prostate Cancer: A Multicenter Phase 1 Study.
Anticancer Res. 2016; 36(12):6499-6504 [PubMed] Related Publications
BACKGROUND: Osteodex (ODX) is a cytotoxic bone-targeting polybisphosphonate, intended for treatment of bone metastasis from castration-resistant prostate cancer (CRPC). The primary objective of this study was to describe the tolerability and toxicity of such treatment by defining its maximum tolerated dose (MTD) and dose-limiting toxicity (DLT).
PATIENTS AND METHODS: Twenty-eight patients with castration-resistant prostate cancer and confirmed bone metastasis were assigned to seven infusions of ODX every third week, divided in seven ascending dose cohorts.
RESULTS: No DLT's were observed and as pre-specified, the highest dose administered was defined as MTD. In total, 206 adverse events (AE) were recorded and 13,6% were classified as treatment-related, while none were serious or severe (SAE). No cumulative toxicity and no renal toxicity were recorded.
CONCLUSION: ODX was well tolerated, with few and mild side-effects and with apparent treatment efficacy in the highest dose cohort. Further clinical development is currently in progress.

Grávalos C, Rodríguez C, Sabino A, et al.
SEOM Clinical Guideline for bone metastases from solid tumours (2016).
Clin Transl Oncol. 2016; 18(12):1243-1253 [PubMed] Article available free on PMC after 03/07/2017 Related Publications
Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.

Pyo JY, Kim J, Choi SE, et al.
Extremely Well-Differentiated Papillary Thyroid Carcinoma Resembling Adenomatous Hyperplasia Can Metastasize to the Skull: A Case Report.
Yonsei Med J. 2017; 58(1):255-258 [PubMed] Article available free on PMC after 03/07/2017 Related Publications
We describe herein histologic, immunohistochemical, and molecular findings and clinical manifestations of a rare case of an extremely well differentiated papillary thyroid carcinoma (EWD-PTC). Similarly, it is also difficult to diagnose follicular variant papillary thyroid carcinoma (FVPTC), whose diagnosis is still met with controversy. A recently reported entity of well-differentiated tumor of uncertain malignant potential (WDT-UMP) is added to the diagnostic spectrum harboring EWD-PTC and FVPTC. We report this case, because EWD-PTC is different from FVPTC in its papillary architecture, and also from WDT-UMP in its recurrence and metastatic pattern. These morphologically deceptive entities harbored diagnostic difficulties in the past because the diagnosis depended solely on histology. However, they are now diagnosed with more certainty by virtue of immunohistochemical and molecular studies. We experienced a case of EWD-PTC, which had been diagnosed as adenomatous hyperplasia 20 years ago and manifested recurrence with lymph node (LN) metastasis 7 years later. After another 7 years of follow-up, a new thyroid lesion had developed, diagnosed as FVPTC, with LN metastasis of EWD-PTC. One year later, the patient developed metastatic FVPTC in the skull. Immunohistochemically, the EWD-PTC was focally positive for CK19, negative for galectin-3, and focally negative for CD56. Molecular studies revealed BRAF-positivity and K-RAS negativity. The FVPTC in the left thyroid showed both BRAF and K-RAS negativity. In conclusion, EWD-PTC and FVPTC share similar histologic features, but they are different tumors with different molecular biologic and clinical manifestations. A large cohort of EWD-PTC should be included in further study.

Body JJ, Terpos E, Tombal B, et al.
Bone health in the elderly cancer patient: A SIOG position paper.
Cancer Treat Rev. 2016; 51:46-53 [PubMed] Related Publications
More than a third of cancers are diagnosed in people over the age of 75. Androgen deprivation for prostate cancer and aromatase inhibitors in breast cancer accelerate age-related bone loss and increase fracture rates. BMD should be checked by dual energy X-ray absorptiometry at baseline and, dependent on risk, every 12-24months. Sufficient calcium, vitamin D and exercise are part of primary fracture prevention. Resistance exercise in particular may improve functional activity and bone density. In men at increased fracture risk and women with postmenopausal early breast cancer, antiresorptive treatment is warranted to reduce fracture rate and to increase overall survival in breast cancer. Bone metastases (BM) are common in breast and prostate cancer and lytic bone lesions typical of multiple myeloma. They can cause fractures, pain and spinal cord compression, require surgery or radiation for symptom relief, and lead to hypercalcaemia. Multidisciplinary working with patients and carers can improve quality of life for elderly patients with BM and mitigate the adverse consequences of therapy. Bisphosphonates and other osteoclast inhibitors such as denosumab reduce this morbidity, improve quality of life and reduce pain. Especially in the elderly, attention should be paid to renal function and to risk factors for osteonecrosis with bone-modifying agents. Attention should also be paid to hypocalcaemia risk, which can be considerable in elderly men with metastatic prostate cancer and vitamin D deficiency. We urgently need further research specifically directed at assessing risks and benefits of bone targeted treatments in the growing population of elderly cancer patients.

Paulino Pereira NR, Langerhuizen DW, Janssen SJ, et al.
Are perioperative allogeneic blood transfusions associated with 90-days infection after operative treatment for bone metastases?
J Surg Oncol. 2016; 114(8):997-1003 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: We assessed whether allogeneic blood transfusions were associated with infection-within 90 days-after surgery for bone metastatic disease. Furthermore, we assessed other risk factors associated with infection.
METHODS: We included 1,266 patients surgically treated for a bone metastasis at two hospitals between 2002 and 2013. Blood transfusions within 7 days before and after surgery were considered perioperative.
RESULTS: We found no independent association between exposure to blood transfusion and infection (odds ratio [OR] 1.02, 95% confidence interval [CI]: 0.76-1.37, P = 0.889), nor a dose-response relationship (OR 1.02, 95%CI: 0.98-1.07, P = 0.245). Older age (OR 1.01, 95%CI: 1.00-1.02, P = 0.035), a higher modified Charlson comorbidity index (OR 1.13, 95%CI: 1.05-1.22, P = 0.002), surgery to the axial skeleton (OR 1.89, 95%CI: 1.42-2.51, P < 0.001), and previous radiotherapy (OR 1.45, 95%CI 1.07-1.96, P = 0.015) were independently associated with infection.
CONCLUSIONS: There was no association between allogeneic blood transfusion and infection. We found other risk factors that should be taken into consideration when deciding to operate. J. Surg. Oncol. 2016;114:997-1003. © 2016 Wiley Periodicals, Inc.

Li W, Li W, Zhang R
Metastasis to the Medial Cuneiform Bone from Squamous Cell Carcinoma of the Lung Revealed by Bone Scintigraphy.
Clin Nucl Med. 2016; 41(12):946-947 [PubMed] Related Publications
A 61-year-old man with a history of squamous cell carcinoma of the lung presented with a progressive left foot pain for 7 months. Bone scan was acquired to evaluate possible metastasis, which showed abnormal accumulation of Tc-MDP in the left foot, which was seen in the medial cuneiform bone on SPECT/CT images. Histopathological examination from biopsy specimen confirmed cuneiform bone metastasis from lung squamous carcinoma.

Ma Y, Wallace AN, Madaelil TP, Jennings JW
Treatment of osseous metastases using the Spinal Tumor Ablation with Radiofrequency (STAR) system.
Expert Rev Med Devices. 2016; 13(12):1137-1145 [PubMed] Related Publications
INTRODUCTION: Percutaneous ablation is an emerging, minimally invasive therapy for patients with osseous metastases who have not responded or have contraindications to radiation therapy. Goals of therapy are pain relief, and in some cases, prevention of local tumor progression. Areas covered: The epidemiology, pathophysiology, natural history, and traditional management of metastatic bone disease are reviewed. Novel features of the Spinal Tumor Ablation with Radiofrequency (STAR) System (DFINE, San Jose, CA) that facilitate treatment of osseous metastases are described, including the bipolar electrode, extensible distal tip that can be curved up to 90°, and inclusion of thermocouples that enable real-time monitoring of the ablation zone volume. Lastly, research evaluating the safety and efficacy of using this device to treat musculoskeletal metastases is summarized. Expert commentary: Although evidence supporting the efficacy of RFA for the treatment of bone metastases is limited to case series, it is a reasonable therapy when other options have been exhausted, especially given the safety and minimal morbidity of the procedure. The STAR Tumor Ablation System has expanded the anatomic scope of bone metastases that can be safely and effectively treated with percutaneous ablation.

Hashmi A, Guckenberger M, Kersh R, et al.
Re-irradiation stereotactic body radiotherapy for spinal metastases: a multi-institutional outcome analysis.
J Neurosurg Spine. 2016; 25(5):646-653 [PubMed] Related Publications
OBJECTIVE This study is a multi-institutional pooled analysis specific to imaging-based local control of spinal metastases in patients previously treated with conventional external beam radiation therapy (cEBRT) and then treated with re-irradiation stereotactic body radiotherapy (SBRT) to the spine as salvage therapy, the largest such study to date. METHODS The authors reviewed cases involving 215 patients with 247 spinal target volumes treated at 7 institutions. Overall survival was calculated on a patient basis, while local control was calculated based on the spinal target volume treated, both using the Kaplan-Meier method. Local control was defined as imaging-based progression within the SBRT target volume. Equivalent dose in 2-Gy fractions (EQD2) was calculated for the cEBRT and SBRT course using an α/β of 10 for tumor and 2 for both spinal cord and cauda equina. RESULTS The median total dose/number of fractions of the initial cEBRT was 30 Gy/10. The median SBRT total dose and number of fractions were 18 Gy and 1, respectively. Sixty percent of spinal target volumes were treated with single-fraction SBRT (median, 16.6 Gy and EQD2/10 = 36.8 Gy), and 40% with multiple-fraction SBRT (median 24 Gy in 3 fractions, EQD2/10 = 36 Gy). The median time interval from cEBRT to re-irradiation SBRT was 13.5 months, and the median duration of patient follow-up was 8.1 months. Kaplan-Meier estimates of 6- and 12-month overall survival rates were 64% and 48%, respectively; 13% of patients suffered a local failure, and the 6- and 12-month local control rates were 93% and 83%, respectively. Multivariate analysis identified Karnofsky Performance Status (KPS) < 70 as a significant prognostic factor for worse overall survival, and single-fraction SBRT as a significant predictive factor for better local control. There were no cases of radiation myelopathy, and the vertebral compression fracture rate was 4.5%. CONCLUSIONS Re-irradiation spine SBRT is effective in yielding imaging-based local control with a clinically acceptable safety profile. A randomized trial would be required to determine the optimal fractionation.

Kitamura H, Takahashi A, Takei F, et al.
Molecular-targeted Therapy and Surgery May Prolong Survival of Renal Cell Carcinoma Patients with Bone Metastasis: A Multi-institutional Retrospective Study in Japan.
Anticancer Res. 2016; 36(10):5531-5536 [PubMed] Related Publications
AIM: To determine prognostic factors for overall survival (OS) in renal cell carcinoma (RCC) patients with bone metastasis in the targeted-therapy era.
PATIENTS AND METHODS: We conducted a retrospective multi-institutional review of the medical records of 149 RCC patients with bone metastasis. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify independent factors associated with OS.
RESULTS: The median OS was 13.4 months. In multivariate analysis, molecular-targeted therapy, nephrectomy and surgery for bone metastasis were independent prognostic factors. Bone-modifying agents (BMAs) were not associated with OS. The median OS of patients receiving molecular-targeted therapy after diagnosis of bone metastasis was significantly better than that of those who did not receive targeted therapy.
CONCLUSION: Molecular-targeted therapy, nephrectomy and surgery for bone metastasis should be considered for RCC patients with metastasis in the bones.

Janssen S, Bajrovic A, Schild SE, Rades D
A Scoring Instrument to Predict the Survival Prognoses of Patients with Metastatic Epidural Spinal Cord Compression from Gynecological Malignancies.
Anticancer Res. 2016; 36(10):5469-5472 [PubMed] Related Publications
AIM: To design a scoring instrument for rating overall survival (OS) of patients with metastatic epidural sinal cord compression (MESCC) from gynecological malignancies.
PATIENTS AND METHODS: In 22 patients treated with radiotherapy alone for MESCC from gynecological malignancies, ten factors were analyzed for effects on OS. Factors significantly associated with OS on multivariate analysis were included in a scoring instrument.
RESULTS: On multivariate analyses, no visceral metastases (p=0.004) and affection of 1-2 vertebrae (p=0.012) were significant. Scoring points for each factor were 0 or 1, depending on OS rates. After summing, scores of 0 (n=6), 1 (n=9) or 2 points (n=9) were obtained. OS rates were 0%, 78% and 100%, respectively, at 3 months and 0%, 33% and 86%, respectively, at 6 months (p<0.001).
CONCLUSION: An instrument was developed for estimating the lifespan of patients with MESCC from gynecological malignancies. This instrument can support physicians when picking an individual treatment.

Buroni FE, Persico MG, Pasi F, et al.
Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer.
Anticancer Res. 2016; 36(11):5719-5730 [PubMed] Related Publications
(223)Ra prolongs overall survival in symptomatic patients affected by multiple bone-metastatic castration-resistant prostatic cancer, without visceral or nodal involvement. However, many questions remain about its mechanisms of action, and its use in clinical practice is still unresolved. First of all, what is the main target of alpha-particle emission, that is, in what way does it influences the tumor microenvironment? When is the best timing in the course of the disease, extending its use to asymptomatic low-volume or even to the micrometastatic phase? What are suitable biomarkers to be employed as prognostic factors and response indicators? Which associations with other drugs and their sequence can offer the best results, and is their effect additive or synergistic? Ultimately, in the current climate of spending review, what is the optimal cost and benefit ratio regarding available treatments? In this review, we tried to answer these questions by analyzing the available scientific literature.

Janssen SJ, Paulino Pereira NR, Raskin KA, et al.
A comparison of questionnaires for assessing physical function in patients with lower extremity bone metastases.
J Surg Oncol. 2016; 114(6):691-696 [PubMed] Related Publications
OBJECTIVES: To assess, (i) the degree to which the: PROMIS Physical Function Cancer, PROMIS Neuro-QoL Mobility, Toronto Extremity Salvage Score (TESS), Lower Extremity Function Score (LEFS), and Musculoskeletal Tumor Society score (MSTS), measure physical function; (ii) differences in coverage and reliability; and (iii) difference in completion time.
METHODS: One hundred of 115 (87%) patients with lower extremity metastases participated in this prospective study. We used exploratory factor analysis-correlating questionnaires with an underlying trait-to assess if questionnaires measure the same. Coverage was assessed by floor and ceiling effect and reliability by the standard error of measurement (SEM). Completion time was compared using the Friedman test.
RESULTS: All questionnaires measured the same concept; demonstrated by high correlations (>0.7). Floor effect was absent, while ceiling effect was present in all, but highest for the PROMIS Neuro-QoL Mobility (7%). The SEM was below the threshold-indicating reliability-over a wide range of ability levels for the PROMIS-Physical Function, TESS, and LEFS. Completion time differed between questionnaires (P < 0.001) and was shortest for the PROMIS questionnaires.
CONCLUSIONS: The PROMIS Physical Function is the most useful questionnaire. This is due to its reliability over a wide range of ability levels, validity, brevity, and good coverage. J. Surg. Oncol. 2016;114:691-696. © 2016 Wiley Periodicals, Inc.

Xie GL, Guo DP, Li ZG, et al.
Application of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia for controlling refractory pain induced by rib metastasis of lung cancer (a STROBE-compliant article).
Medicine (Baltimore). 2016; 95(40):e4785 [PubMed] Article available free on PMC after 03/07/2017 Related Publications
This study aimed to observe the therapeutic effects and adverse reactions of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia on lung cancer rib metastasis-related refractory pain which has no response to conventional therapy.This study contained 27 patients with lung cancer rib metastasis-related moderate or severe pain which had no response to conventional therapy. Under computed tomography (CT)-guidance, radiofrequency puncture need reached the corresponding intervertebral foramens to ensure needle point near dorsal root ganglia (DRG) by sensory and motor stimulation tests, and then radiofrequency thermocoagulation was performed on each corresponding DRG followed by injection of 0.5 to 1 mL of adriamycin (0.5%). The conditions of pain and complications were observed before management and 3 days, 1 month, and 3 months after management, respectively.Numerical rating scale (NRS) scores and dosage of morphine were all significantly decreased after management as compared with those before management (all P < 0.01). Although the number of patients with chest wall numbness was significantly increased after management as compared with that before management (all P < 0.01), the degree of chest wall numbness was tolerable. There were no statistical differences between before and after management in nausea and vomiting, and constipation.CT-guided radiofrequency thermocoagulation combined with adriamycin injection in DRG can effectively control lung cancer rib metastasis-related pain which has no response to conventional therapy. This combinatory treatment regimen is featured by better therapeutic effects and a few complications, so it is worthy of being recommended in clinical application.

Charles NC, Petris CK, Kim ET
Aggressive esthesioneuroblastoma with divergent differentiation: A taxonomic dilemma.
Orbit. 2016; 35(6):357-359 [PubMed] Related Publications
The authors describe an esthesioneuroblastoma (olfactory neuroblastoma) that occurred within the nasal cavity and brain in a 31-year-old man. Following excision, the tumor recurred in the left orbit and in mediastinal lymph nodes. Treatment included orbital excision and systemic chemotherapy. Histopathology showed a high-grade neuroepithelial tumor with positive immunohistochemical markers for neuroendocrine and epithelial components, an unusual combination raising issues concerning taxonomy.

Urano M, Maki Y, Nishikawa H, et al.
Diagnostic utility of a computer-aided diagnosis system for whole-body bone scintigraphy to detect bone metastasis in breast cancer patients.
Ann Nucl Med. 2017; 31(1):40-45 [PubMed] Related Publications
OBJECTIVE: To compare the diagnostic ability of planar images (PI) and images obtained by a computer-aided diagnosis (CAD) system (Viewer for Standardized Bone Scintigraphies; VSBONE) of whole-body bone scintigraphy for detecting bone metastases in breast cancer patients.
METHODS: 81 women (median: 56 years; range: 32-79) with a history of breast cancer were included in this study. They underwent whole-body bone scintigraphy after intravenous injection of 740 MBq technetium-99m hydroxymethylene diphosphonate. A total of 1066 bones (162 regions of the skull, 657 regions of the spine and pelvis, 223 regions of the sternum and rib, 18 regions of the upper extremities, and 6 regions of the lower extremities) were analyzed. The PI alone, VSBONE images alone, and both PI and VSBONE images (PI + VSBONE) were interpreted independently by two radiologists to diagnose bone metastases, which were then confirmed by magnetic resonance imaging. The sensitivity and specificity for each modality were analyzed using Fisher's exact and McNemar tests. Inter-reviewer agreement was evaluated using a kappa statistic.
RESULTS: Bone metastases were confirmed in 43 patients with 442 positive lesions. The average sensitivity of PI, VSBONE images, and PI + VSBONE images was 40.8, 50.2, and 61.8 %, respectively. The average specificity was 97.8, 97.5, and 97.6 %, respectively. The kappa scores were 0.62 for PI, 0.69 for VSBONE, and 0.77 for PI + VSBONE.
CONCLUSIONS: VSBONE was superior to PI in regard to sensitivity for detecting bone metastases in breast cancer patients. However, an improved CAD system is required to decrease the number of false-negative results.

Stathopoulos GP, Trafalis D, Kaparelou M
Bone metastasis in breast cancer is treated by high-dose tamoxifen.
J BUON. 2016 Jul-Aug; 21(4):1013-1015 [PubMed] Related Publications
PURPOSE: Bone metastases in breast cancer are quite common, and some patients may have no other site of metastasis. An effective treatment is often endocrine agents administration (tamoxifen or antiaromatases), given mainly to postmenopausal women. Radiation treatment is also effective, although difficult to perform in cases of extensive skeletal disease. Chemotherapy does not help. The purpose of this study was to investigate the effectiveness of high-dose tamoxifen in female patients with breast cancer and bone metastasis.
METHODS: 28 patients with breast cancer were treated with high-dose tamoxifen. All of them had been pretreated with hormonal therapy including low-dose tamoxifen.
RESULTS: The results were extremely positive with clinical amelioration and also disappearance of osteolysis in some patients. Twenty six out of 28 patients responded to the treatment, the criteria being mainly pain reduction and body mobilization (an amelioration which lasted 8 months-4 years).
CONCLUSION: Tamoxifen is efficient when readministered at high dose to breast cancer patient with bone metastasis.

Ambelil M, Sultana S, Roy S, Gonzalez MM
Anaplastic Transformation in Mandibular Metastases of Follicular Variant of Papillary Thyroid Carcinoma: A Case Report and Review of the Literature.
Ann Clin Lab Sci. 2016; 46(5):552-6 [PubMed] Related Publications
Anaplastic transformation of well-differentiated thyroid carcinomas at distant metastatic sites is a rare condition. Most cases described in the literature have occurred in the thyroid or regional lymph nodes. We report a case of anaplastic transformation of the follicular variant of papillary thyroid carcinoma in mandibular metastases. A 76-year-old female presented with a painful and enlarging mandibular mass. She had been treated in the past for the follicular variant of papillary thyroid carcinoma. A palliative hemi-mandibulectomy was performed. Histology revealed a metastatic papillary thyroid carcinoma, follicular variant, with an unusual finding of solid pleomorphic epithelioid and spindle cell areas, consistent with anaplastic transformation.

Donati F, Di Giacomo G, D'Adamio S, et al.
Silver-Coated Hip Megaprosthesis in Oncological Limb Savage Surgery.
Biomed Res Int. 2016; 2016:9079041 [PubMed] Article available free on PMC after 03/07/2017 Related Publications
Silver coating has demonstrated good antimicrobial activity and low toxicity. Silver-coated megaprostheses have been introduced in oncological musculoskeletal surgery considering the high rate of infection. We conducted a retrospective analysis on 68 cases of primary or metastatic bone tumors, affecting the proximal femur, treated between 2005 and 2016 with wide margins resection and tumor implants reconstruction. All patients were treated by the same surgeon, with antibiotic prophylaxis according to a standard protocol. In 55.9% of patients silver-coated hip hemiarthroplasty was implanted; in the remaining 44.1% uncoated megaprostheses were implanted. Patients were reevaluated recording the complications and focusing the analysis on infective complications. The average follow-up was 46.5 months. No patient has shown any sign of local or general silver toxicity. A SEM analysis was conducted on the 3-silver-coated hip hemiarthroplasty explanted confirming a severe degradation with a small amount of residual silver on the coating surface. Silver-coated hip prostheses have a lower rate of early infection than traditional implants but showed a reduction of antimicrobial activity for silver coating wear. We recommend using silver-coated prosthesis as primary implants for limb salvage surgery, in primary or metastatic bone tumors affecting the proximal femur, considering the absence of signs of toxicity and the lower rate of early infection.

Kulshrestha RK, Vinjamuri S, England A, et al.
The Role of 18F-Sodium Fluoride PET/CT Bone Scans in the Diagnosis of Metastatic Bone Disease from Breast and Prostate Cancer.
J Nucl Med Technol. 2016; 44(4):217-222 [PubMed] Related Publications
We describe the role of (18)F-sodium fluoride ((18)F-NaF) PET/CT bone scanning in the staging of breast and prostate cancer. (18)F-NaF PET was initially utilized as a bone scanning agent in the 1960s and early 1970s, however, its use was restricted by the then-available γ-cameras. The advent of hybrid PET/CT cameras in the late 1990s has shown a resurgence of interest in its use and role. After a brief introduction, this paper describes the radiopharmaceutical properties, dosimetry, pharmacokinetics, and mechanism of uptake of (18)F-NaF. The performance of (18)F-NaF PET/CT is then compared with that of conventional bone scintigraphy using current evidence from the literature. Strengths and weaknesses of (18)F-NaF PET/CT imaging are highlighted. Clinical examples of improved accuracy of diagnosis and impact on patient management are illustrated. Limitations of (18)F-NaF PET/CT imaging are outlined.

Tun K, Bulut T
Triple orbital metastases from prostate cancer.
Neurol Neurochir Pol. 2016; 50(5):392-4 [PubMed] Related Publications
Prostate carcinoma, when metastatic, typically involves bone and produces both osteoblastic and osteolytic changes. A 73-year-old man was admitted to our department because of unilateral progressive proptosis and visual blurriness for 3 months. The patient had a history of prostate adenocarcinoma diagnosis 5 years ago. We report a case of orbital involvement presented that intraorbital mass (including periocular structures), temporal bone and temporal muscle from prostate cancer. The mass was removed with total excision. Despite the frequency of bone metastasis in prostatic carcinoma, triple orbital metastases are extremely rare. The best of our knowledge, prostate adenocarcinoma and its triple (temporal bone, temporal muscle and intraorbital mass) orbital metastases have not been published previously. Metastatic orbital tumor secondary to prostate cancer should be considered in patients who have varying degrees of eye symptoms.

Anzidei M, Napoli A, Sacconi B, et al.
Magnetic resonance-guided focused ultrasound for the treatment of painful bone metastases: role of apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) MRI in the assessment of clinical outcome.
Radiol Med. 2016; 121(12):905-915 [PubMed] Related Publications
PURPOSE: To assess the correlation between functional MRI, including ADC values obtained from DWI and DCE, and clinical outcome in patients with bone metastases treated with MRgFUS.
METHODS AND MATERIALS: Twenty-three patients with symptomatic bone metastases underwent MRgFUS treatment (ExAblate 2100 system InSightec) for pain palliation. All patients underwent clinical and imaging follow-up examinations at 1, 3 and 6 months after treatment. Visual Analog Scale (VAS) score was used to evaluate treatment efficacy in terms of pain palliation while ADC maps obtained by DWI sequences, and DCE data were used for quantitative assessment of treatment response at imaging. Spearman Correlation Coefficient Test was calculated to assess the correlation between VAS, ADC and DCE data.
RESULTS: All treatments were performed successfully without adverse events. On the basis of VAS score, 16 (69.6 %) patients were classified as complete clinical responders, 6 (26.1 %) as partial responders and only one (4.3 %) was classified as a non-responder. The mean VAS score decreased from 7.09 ± 1.8 at baseline to 2.65 ± 1.36 at 1 month, 1.04 ± 1.91 at 3 months and 1.09 ± 1.99 at 6 months (p < 0.001). Baseline mean ADC value of treated lesions was 1.05 ± 0.15 mm(2)/s, increasing along follow-up period (1.57 ± 0.27 mm(2)/s 1st month; 1.49 ± 0.3 mm(2)/s 3rd month; 1.45 ± 0.32 mm(2)/s 6th month, p < 0.001). Non perfused volume (NPV) was 46.4 at 1 month, 45.2 at 3 months and 43.8 at 6 months. Spearman Coefficient demonstrated a statistically significant negative correlation between VAS and ADC values (ρ = -0.684; p = 0.03), but no significant correlation between VAS and NPV (ρ = 0.02216, p = 0.9305). Among other DCE data, Ktrans significantly changed in complete responders (3 months Ktrans = 2.14/min; -ΔKt = 52.65 % p < 0.01) and was not significantly different in partial responders (3 months Ktrans 0.042/min; ΔKt = 11.39 % p > 0.01).
CONCLUSION: In patients with painful bone metastases treated with MRgFUS, ADC and Ktrans variation observed in the ablated lesions correlate with VAS values and may play a role as objective imaging marker of treatment response.

Ferreira Ddos S, Faria SD, Lopes SC, et al.
Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis.
Int J Nanomedicine. 2016; 11:3737-51 [PubMed] Article available free on PMC after 03/07/2017 Related Publications
BACKGROUND: Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges.
PURPOSE: To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX) in an acidic environment for future application as a tool for treatment of bone metastases.
MATERIALS AND METHODS: Liposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, ζ-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5), plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was assessed in bone metastasis-bearing animals.
RESULTS: Liposomes presented suitable diameter (~170 nm), DOX encapsulation (~2 mg/mL), controlled release, and good plasma and serum stability. The existence of interactions between DOX and the lipid bilayer was proved through differential scanning calorimetry and small-angle X-ray scattering. DOX release was faster when the pH was in the range of a tumor than at physiological pH. The bone-targeted formulation showed a strong affinity for hydroxyapatite. The encapsulation of DOX did not interfere in its intrinsic cytotoxicity against the MDA-MB-231 cell line. Biodistribution studies demonstrated high affinity of this formulation for tumors and reduction of uptake in the heart.
CONCLUSION: These results suggest that bone-targeted pH-sensitive liposomes containing DOX can be an interesting strategy for selectively delivering this drug into bone-tumor sites, increasing its activity, and reducing DOX-related toxicity.

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