Secondary Bone Cancer (bone metastasis)
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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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Bone Cancer

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Latest Research Publications

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

Sugimoto S, Tanaka M, Suzawa K, et al.
Pneumocephalus and chylothorax complicating vertebrectomy for lung cancer.
Ann Thorac Surg. 2015; 99(4):1425-8 [PubMed] Related Publications
Pneumocephalus is a rare, but potentially fatal complication of thoracic surgery. We describe a case of successful management of pneumocephalus complicated by persistent chylothorax developing after en bloc partial vertebrectomy performed after induction chemoradiotherapy for lung cancer invading the spine. Surgical treatment should be considered for pneumocephalus complicated by any condition requiring persistent chest drainage.

Related: Lung Cancer

Bowers B
Recognising metastatic spinal cord compression.
Br J Community Nurs. 2015; 20(4):162-5 [PubMed] Related Publications
Metastatic spinal cord compression (MSCC) is a potentially life changing oncological emergency. Neurological function and quality of life can be preserved if patients receive an early diagnosis and rapid access to acute interventions to prevent or reduce nerve damage. Symptoms include developing spinal pain, numbness or weakness in arms or legs, or unexplained changes in bladder and bowel function. Community nurses are well placed to pick up on the 'red flag' symptoms of MSCC and ensure patients access prompt, timely investigations to minimise damage.

Chan HP, Hu C, Yu CC, et al.
Added value of using a cocktail of F-18 sodium fluoride and F-18 fluorodeoxyglucose in positron emission tomography/computed tomography for detecting bony metastasis: a case report.
Medicine (Baltimore). 2015; 94(13):e687 [PubMed] Related Publications
Current nuclear imaging of the skeletal system is achieved using technetium-99m (Tc-99m) methylene diphosphonate (MDP), F-18 sodium fluoride (NaF), or F-18 fluorodeoxyglucose (FDG). However, comparisons of these are rare in the literature. We present a case of a 51-year-old female with suspicious lung cancer due to main symptoms of dyspnea, nonproductive cough, and pleural pain. Tc-99m MDP whole-body bone scan (WBBS) showed multiple bony metastases. Five days later, positron emission tomography/computed tomography (PET/CT) images using both F-18 NaF and a cocktail of F-18 NaF and F-18 FDG were obtained on the same day 2 hours apart. The former showed more foci and precisely showed bony lesions compared to those obtained using Tc-99m MDP WBBS. However, the latter demonstrated more extensive radiotracer uptake, especially in osteolytic lesions, and additional soft tissue lesions in the left axillary and surpraclavicular nodes as well as the left pleura. Surgical biopsy was performed in left axillary nodes, and the metastatic carcinoma was found to be of breast origin. This case demonstrated that a cocktail of F-18 NaF and F-18 FDG could be useful in PET/CT for not only detecting more skeletal lesions but also guiding biopsies accurately to the affected tissue.

Related: Breast Cancer

Tseng CL, Sussman MS, Atenafu EG, et al.
Magnetic resonance imaging assessment of spinal cord and cauda equina motion in supine patients with spinal metastases planned for spine stereotactic body radiation therapy.
Int J Radiat Oncol Biol Phys. 2015; 91(5):995-1002 [PubMed] Related Publications
PURPOSE: To assess motion of the spinal cord and cauda equina, which are critical neural tissues (CNT), which is important when evaluating the planning organ-at-risk margin required for stereotactic body radiation therapy.
METHODS AND MATERIALS: We analyzed CNT motion in 65 patients with spinal metastases (11 cervical, 39 thoracic, and 24 lumbar spinal segments) in the supine position using dynamic axial and sagittal magnetic resonance imaging (dMRI, 3T Verio, Siemens) over a 137-second interval. Motion was segregated according to physiologic cardiorespiratory oscillatory motion (characterized by the average root mean square deviation) and random bulk shifts associated with gross patient motion (characterized by the range). Displacement was evaluated in the anteroposterior (AP), lateral (LR), and superior-inferior (SI) directions by use of a correlation coefficient template matching algorithm, with quantification of random motion measure error over 3 separate trials. Statistical significance was defined according to P<.05.
RESULTS: In the AP, LR, and SI directions, significant oscillatory motion was observed in 39.2%, 35.1%, and 10.8% of spinal segments, respectively, and significant bulk motions in all cases. The median oscillatory CNT motions in the AP, LR, and SI directions were 0.16 mm, 0.17 mm, and 0.44 mm, respectively, and the maximal statistically significant oscillatory motions were 0.39 mm, 0.41 mm, and 0.77 mm, respectively. The median bulk displacements in the AP, LR, and SI directions were 0.51 mm, 0.59 mm, and 0.66 mm, and the maximal statistically significant displacements were 2.21 mm, 2.87 mm, and 3.90 mm, respectively. In the AP, LR, and SI directions, bulk displacements were greater than 1.5 mm in 5.4%, 9.0%, and 14.9% of spinal segments, respectively. No significant differences in axial motion were observed according to cord level or cauda equina.
CONCLUSIONS: Oscillatory CNT motion was observed to be relatively minor. Our results support the importance of controlling bulk patient motion and the practice of applying a planning organ-at-risk margin.

Humm JL, Sartor O, Parker C, et al.
Radium-223 in the treatment of osteoblastic metastases: a critical clinical review.
Int J Radiat Oncol Biol Phys. 2015; 91(5):898-906 [PubMed] Related Publications
The element radium (Ra) was discovered by the Curies in 1898 and within a decade was in broad scientific testing for the management of several forms of cancer. The compound was known to give rise to a series of both high-energy particulate and penetrating γ-emissions. The latter found an important role in early 20th century brachytherapy applications, but the short-range α-particles seemed much less useful. Although highly cytotoxic when released within a few cell diameters of critical cell nuclei, the dense double-strand break damage was poorly repaired, and concerns regarding treatment-related toxicities and secondary malignancies halted clinical development. Moreover, the most common isotope of Ra has an exceptionally long half-life (>1600 years for (226)Ra) that proved daunting when aiming for a systemic cancer therapy. Fortunately, other radium isotopes have more convenient half-lives while still producing cytotoxic α particles. Radium-223 dichloride has a half-life of 11.4 days, and this isotope was identified as an excellent candidate for radionuclide therapy of cancers metastatic to bone. The calcium-mimetic chemical properties of the radium allowed intravenous infusion with rapid uptake to sites of new bone formation. The highly efficient bone localization suggested a potential therapeutic role for osteoblastic bone metastases, and a series of phase 1, 2, and 3 clinical trials was undertaken to explore this possibility. This series of clinical explorations culminated in the ALSYMPCA trial, an international, placebo-controlled, phase 3 study that accrued 921 symptomatic men with bone-metastatic, castrate-resistant prostate cancer. Results of this trial demonstrated a prolongation of overall survival, and regulatory agencies around the world have now approved this product as a treatment for advanced prostate cancer.

Related: Breast Cancer Myeloma Myeloma - Molecular Biology Osteosarcoma

Hardaway AL, Herroon MK, Rajagurubandara E, Podgorski I
Marrow adipocyte-derived CXCL1 and CXCL2 contribute to osteolysis in metastatic prostate cancer.
Clin Exp Metastasis. 2015; 32(4):353-68 [PubMed] Article available free on PMC after 01/04/2016 Related Publications
Increased bone marrow adiposity is a common feature of advanced age, obesity and associated metabolic pathologies. Augmented numbers of marrow adipocytes positively correlate with dysregulated bone remodeling, also a well-established complication of metastatic disease. We have shown previously that marrow adiposity accelerates prostate tumor progression in the skeleton and promotes extensive destruction of the bone; however, the factors behind adipocyte-driven osteolysis in the skeletal tumor microenvironment are not currently known. In this study, utilizing in vivo diet-induced models of bone marrow adiposity, we reveal evidence for positive correlation between increased marrow fat content, bone degradation by ARCaP(M) and PC3 prostate tumors, and augmented levels of host-derived CXCL1 and CXCL2, ligands of CXCR2 receptor. We show by in vitro osteoclastogenesis assays that media conditioned by bone marrow adipocytes is a significant source of CXCL1 and CXCL2 proteins. We also demonstrate that both the adipocyte-conditioned media and the recombinant CXCL1 and CXCL2 ligands efficiently accelerate osteoclast maturation, a process that can be blocked by neutralizing antibodies to each of the chemokines. We further confirm the contribution of CXCR2 signaling axis to adiposity-driven osteoclastogenesis by blocking fat cell-induced osteoclast differentiation with CXCR2 antagonist or neutralizing antibodies. Together, our results link CXCL1 and CXCL2 chemokines with bone marrow adiposity and implicate CXCR2 signaling in promoting effects of marrow fat on progression of skeletal tumors in bone.

Related: CXCL1 CXCL2 Prostate Cancer

Dibekoglu C, Turanli S, Karaman N, et al.
Bone fracture in breast cancer patients with isolated bone metastasis.
Chirurgia (Bucur). 2015 Jan-Feb; 110(1):43-8 [PubMed] Related Publications
AIM: To analyse the incidence of bone fracture of breast cancer patients with isolated bone metastasis and its effect on survival. We tried to find an answer to the question of "Can the development of bone fracture be predicted?"
METHODS: Between 1993-2006, 139 breast cancer patients with isolated bone metastasis were examined. Patients were divided into two groups depending on the development of pathologic bone fracture.
RESULTS: Fractures were developed in 41 patients (29.5%)within 41 months of follow-up. The locations of pathologic bone fracture were vertebral fracture in 26 patients (63.4%),femur fracture in 11 patients (26.8%), and hip fracture in four patients (9.8%). Fracture rates in hormone sensitive and resistant patients were 31.2% and 14.3%, respectively. The fracture rates in 13 triple negative and non triple negative patients were 7.7% and 31.4%, respectively (p=0.07). High CA 15-3 levels at the time of metastasis in patients with and without fractures were 68.4% and 61.1%, respectively. The risk for fracture was also high in Her2-neu positive patients (38.7% vs. 26.5%). While the incidence of fracture with the presence of one factor mentioned above was 22.2%, it was increased to 36.1% in the presence of two or three factors(p=0.13). Median survivals of the patients with and without fractures were 48 and 39 months, respectively (p= 0.65).
CONCLUSION: Hormone sensitivity, high CA 15-3 levels and positive Her2-neu status are slight risk factors for bone fractures. Survival was not different in patients with or without bone fractures.

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Soni A, Ren Z, Hameed O, et al.
Breast cancer subtypes predispose the site of distant metastases.
Am J Clin Pathol. 2015; 143(4):471-8 [PubMed] Related Publications
OBJECTIVES: The distant organs to which breast cancer preferentially metastasizes are of significant clinical importance.
METHODS: We explored the relationship between the clinicopathologic factors and the common sites of distant metastasis in 531 consecutive patients with advanced breast cancer.
RESULTS: Breast cancer subtype as a variable was significantly associated with all five common sites of relapse by multivariate analysis. The luminal tumors were remarkable for their significant bone-seeking phenotype and were less frequently observed in lung, brain, and pleural metastases and less likely to be associated with multiorgan relapse. The HER2 subtype demonstrated a significant liver-homing characteristic. African Americans were significantly less likely to have brain-only metastasis in patients with brain relapse.
CONCLUSIONS: These findings further articulate that breast cancer subtypes differ not only in tumor characteristics but also in their metastatic behavior, thus raising the possibility that this knowledge could potentially be used in determining the appropriate strategy for follow-up of patients with newly diagnosed breast cancer.

Related: Breast Cancer

Mandelin J, Cardó-Vila M, Driessen WH, et al.
Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors.
Proc Natl Acad Sci U S A. 2015; 112(12):3776-81 [PubMed] Article available free on PMC after 01/04/2016 Related Publications
We performed combinatorial peptide library screening in vivo on a novel human prostate cancer xenograft that is androgen-independent and induces a robust osteoblastic reaction in bonelike matrix and soft tissue. We found two peptides, PKRGFQD and SNTRVAP, which were enriched in the tumors, targeted the cell surface of androgen-independent prostate cancer cells in vitro, and homed to androgen receptor-null prostate cancer in vivo. Purification of tumor homogenates by affinity chromatography on these peptides and subsequent mass spectrometry revealed a receptor for the peptide PKRGFQD, α-2-macroglobulin, and for SNTRVAP, 78-kDa glucose-regulated protein (GRP78). These results indicate that GRP78 and α-2-macroglobulin are highly active in osteoblastic, androgen-independent prostate cancer in vivo. These previously unidentified ligand-receptor systems should be considered for targeted drug development against human metastatic androgen-independent prostate cancer.

Luedders DW, Steinhoff J, Thill M, et al.
Lack of difference in acute nephrotoxicity of intravenous bisphosphonates zoledronic acid and ibandronate in women with breast cancer and bone metastases.
Anticancer Res. 2015; 35(3):1797-802 [PubMed] Related Publications
BACKGROUND: More than 50% of patients with advanced breast cancer develop bone metastases that may lead to multiple complications such as pathological fractures, bone pain or hypercalcaemia. The standard treatment, besides endocrine, targeted-therapy or chemotherapy, is the use of bisphosphonates. However, one of their main adverse side-effects is bisphosphonate-induced nephrotoxicity. The mechanism by which the latter occurs is not well-understood, although emerging evidence suggests that the effect of bisphosphonates on the kidney may differ between agents.
PATIENTS AND METHODS: The aim of this evaluation was to compare the renal toxicity of 6 mg ibandronate i.v. versus 4 mg zoledronic acid i.v. over a period of six months in women with breast cancer and bone metastases. A prospective randomized trial was carried out to examine specific kidney and other parameters (α1- and β2-microglobulin, albumin, α2-macroglobulin, IgG and C-reactive protein (CRP) generated from spontaneous urine samples from 17 patients of each group.
RESULTS: We were unable to find any significant difference between the two treatment groups with regard to renal toxicity. All patients, independently of the applied bisphosphonate, experienced only temporary renal dysfunction without any evidence of irreversible damage in terms of acute nephrotoxicity during the study period. α1-Microglobulin, a marker for proximal tubular damage, in particular, was not differently elevated in either group.
CONCLUSION: Both applied bisphosphonates were found to be well-tolerated and safe with regard to renal toxicity during a six-month treatment period in patients with otherwise healthy kidneys having advanced breast cancer and bone metastases.

Related: Breast Cancer Bisphosphonates Zoledronic acid (Zometa)

Sosnoski DM, Norgard RJ, Grove CD, et al.
Dormancy and growth of metastatic breast cancer cells in a bone-like microenvironment.
Clin Exp Metastasis. 2015; 32(4):335-44 [PubMed] Related Publications
Breast cancer can reoccur, often as bone metastasis, many years if not decades after the primary tumor has been treated. The factors that stimulate dormant metastases to grow are not known, but bone metastases are often associated with skeletal trauma. We used a dormancy model of MDA-MB-231BRMS1, a metastasis-suppressed human breast cancer cell line, co-cultured with MC3T3-E1 osteoblasts in a long term, three dimensional culture system to test the hypothesis that bone remodeling cytokines could stimulate dormant cells to grow. The cancer cells attached to the matrix produced by MC3T3-E1 osteoblasts but grew slowly or not at all until the addition of bone remodeling cytokines, TNFα and IL-β. Stimulation of cell proliferation by these cytokines was suppressed with indomethacin, an inhibitor of cyclooxygenase and of prostaglandin production, or a prostaglandin E2 (PGE2) receptor antagonist. Addition of PGE2 directly to the cultures also stimulated cell proliferation. MCF-7, non-metastatic breast cancer cells, remained dormant when co-cultured with normal human osteoblast and fibroblast growth factor. Similar to the MDA-MB-231BRMS1 cells, MCF-7 proliferation increased in response to TNFα and IL-β. These findings suggest that changes in the bone microenvironment due to inflammatory cytokines associated with bone repair or excess turnover may trigger the occurrence of latent bone metastasis.

Related: Breast Cancer TNF IL6

Nagasawa M, Johnin K, Hanada E, et al.
Advanced childhood testicular yolk sac tumor with bone metastasis: a case report.
Urology. 2015; 85(3):671-3 [PubMed] Related Publications
We report a case of advanced childhood testicular yolk sac tumor with bone metastasis, which was successfully treated by multimodal treatment. Optimal management of bone metastases from testicular yolk sac tumor in childhood is discussed.

Related: Testicular Cancer

Gurrieri L, Longhi A, Braghetti A
Lung cancer presenting as a metastasis to the tibial bones: a case report.
Tumori. 2015 Jan-Feb; 101(1):e18-20 [PubMed] Related Publications
AIMS AND BACKGROUND: Bone metastasis below the knee from primary lung cancer is rare. Discussion of such cases in a multidisciplinary team is important to establish the correct treatment approach.
CASE REPORT: We analyzed the diagnostic pathway of a 53-year-old female patient with a 5-month history of pain in the right foot. The patient underwent several radiological examinations for the pain. An initial diagnosis of osteoporotic syndrome was made, followed by a diagnosis of primary sarcoma. Only when the patient continued to have pain were other radiological examinations performed and a biopsy of the right ankle taken. This revealed a metastasis from undifferentiated pulmonary adenocarcinoma. A total-body computed tomography scan did not show any tumor locations apart from the primary lung cancer. The patient underwent chemotherapy and palliative therapies. This case has been reported for its rarity.

Kim H, Rajagopalan MS, Beriwal S, et al.
Cost-effectiveness analysis of single fraction of stereotactic body radiation therapy compared with single fraction of external beam radiation therapy for palliation of vertebral bone metastases.
Int J Radiat Oncol Biol Phys. 2015; 91(3):556-63 [PubMed] Related Publications
PURPOSE: Stereotactic body radiation therapy (SBRT) has been proposed for the palliation of painful vertebral bone metastases because higher radiation doses may result in superior and more durable pain control. A phase III clinical trial (Radiation Therapy Oncology Group 0631) comparing single fraction SBRT with single fraction external beam radiation therapy (EBRT) in palliative treatment of painful vertebral bone metastases is now ongoing. We performed a cost-effectiveness analysis to compare these strategies.
METHODS AND MATERIALS: A Markov model, using a 1-month cycle over a lifetime horizon, was developed to compare the cost-effectiveness of SBRT (16 or 18 Gy in 1 fraction) with that of 8 Gy in 1 fraction of EBRT. Transition probabilities, quality of life utilities, and costs associated with SBRT and EBRT were captured in the model. Costs were based on Medicare reimbursement in 2014. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and effectiveness was measured in quality-adjusted life years (QALYs). To account for uncertainty, 1-way, 2-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay (WTP) threshold of $100,000 per QALY gained.
RESULTS: Base case pain relief after the treatment was assumed as 20% higher in SBRT. Base case treatment costs for SBRT and EBRT were $9000 and $1087, respectively. In the base case analysis, SBRT resulted in an ICER of $124,552 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of the utility of unrelieved pain; the utility of relieved pain after initial treatment and median survival were also sensitive to variation. If median survival is ≥11 months, SBRT cost <$100,000 per QALY gained.
CONCLUSION: SBRT for palliation of vertebral bone metastases is not cost-effective compared with EBRT at a $100,000 per QALY gained WTP threshold. However, if median survival is ≥11 months, SBRT costs ≤$100,000 per QALY gained, suggesting that selective SBRT use in patients with longer expected survival may be the most cost-effective approach.

Akram M, Baig MA, Ali S
Sister Mary Joseph nodule, a forgotten nodule.
J Ayub Med Coll Abbottabad. 2014 Jul-Sep; 26(3):416-8 [PubMed] Related Publications
Metastatic cancer of the umbilicus, known as Sister Mary Joseph nodule, is typically associated with visceral malignancy. It is an uncommon and rare presentation. It indicates disseminated disease and poor prognosis. Physicians need to be aware of this rare clinical condition so that they can promptly diagnose the primary cancer.

Related: Stomach Cancer Gastric Cancer

Basit A, Siddiqui N, Hameed A, et al.
Factors affecting outcome of patients with multiple myeloma.
J Ayub Med Coll Abbottabad. 2014 Jul-Sep; 26(3):376-9 [PubMed] Related Publications
BACKGROUND: Multiple myeloma is a heterogeneous disease, with wide survival range and multiple risk factors and staging systems linked to survival. The objective of this study was to assess the overall survival of patients with multiple myeloma (MM) diagnosed and treated at Shaukat Khanum Memorial Cancer Hospital (SKMCH), Lahore with respect to various prognostic factors.
METHODS: This was a survival analysis with data collected retrospectively on 82 patients fulfilling the diagnostic criteria of multiple myeloma. Overall survival was studied in relation to International Staging System (ISS), renal failure (Serum creatinine >2 mg/dl), anaemia (Hemoglobin <10 mg/dl), bone involvement (presence of lytic lesion on skeletal survey) and hypercalcemia (serum calcium >11mg/dl) due to multiple myeloma at the time of diagnosis.
RESULTS: Mean age of patients was 61 years, including 67% males and 33% females. Median overall survival for ISS stage-I (24%), stage-II (44%) and stage-III (32%) was 58, 41 and 12 months respectively (p=0.01). Patients with renal impairment (16% of total) had median overall survival of 13 months compared to 41 months in patients without renal involvement (p=0.02). Hypercalcemia was noted in 27% patients with median overall survival of 32 months versus 38 months in patients without hypercalcemia, but its impact on survival was statistically insignificant (p=0.79). Similarly no significant impact on survival was noted in patients with bone involvement or anaemia found in 74 % and 38% of patient's respectively.
CONCLUSIONS: ISS stage and renal failure due to multiple myeloma at presentation have a significant impact on survival. However, other prognostic factors like bone involvement, anaemia and hypercalcemia were not shown to influence survival significantly.

Related: Myeloma Myeloma - Molecular Biology

Milojkovic N, Homsi S
Polymethylmethacrylate pulmonary embolism as a complication of percutaneous vertebroplasty in cancer patients.
J Ark Med Soc. 2014; 111(7):140-2 [PubMed] Related Publications
Percutaneous vertebroplasty is frequently used in the treatment of vertebral body fractures due to osteoporosis, vertebral body metastasis, or myeloma. Acrylic cement of polymethylmethacrylate injected into the vertebral body can leak into the paravertebral venous system and reach the pulmonary artery via the azygos vein leading to a cement pulmonary embolism. We are presenting a case of a 78 year old woman who was found to have polymethylmethacrylate pulmonary embolism as a result of vertebroplasty used for vertebral collapse from metastatic breast cancer. The appearance of new intrapulmonary artery tubular opaque density on CXR performed post procedure is highly suggestive of the diagnosis. In this case, we are exploring the importance of clinical and radiographic correlations, as well as evaluation of the hemodynamic and perfusion effect of the cement pulmonary embolism as essential steps in the management of this condition.

Related: Breast Cancer

Ito S, Yoshimura T, Kondo T, et al.
Long-term survival with chest wall resection and pulmonary metastasectomy for hepatocellular carcinoma.
Ann Thorac Surg. 2015; 99(2):695-8 [PubMed] Related Publications
A case of rib and pulmonary metastases of hepatocellular carcinoma (HCC) successfully treated with transcatheter arterial embolization (TAE) followed by surgery is reported. A 66-year-old male with a history of HCC treated previously with hepatectomy was admitted to our hospital for examination of a chest wall tumor. Before the admission, TAE targeting the chest wall tumor was performed. TAE followed by surgery for postresection metastases of HCC was performed and provided an excellent result with long-term survival. The combination of TAE plus salvage surgery could be an option in select patients with limited disease.

Related: Liver Cancer

Bate BG, Khan NR, Kimball BY, et al.
Stereotactic radiosurgery for spinal metastases with or without separation surgery.
J Neurosurg Spine. 2015; 22(4):409-15 [PubMed] Related Publications
OBJECT: In patients with significant epidural spinal cord compression, initial surgical decompression and stabilization of spinal metastases, as opposed to radical oncological resection, provides a margin around the spinal cord that facilitates subsequent treatment with high-dose adjuvant stereotactic radiosurgery (SRS). If a safe margin exists between tumor and spinal cord on initial imaging, then high-dose SRS may be used as the primary therapy, eliminating the need for surgery. Selecting the appropriate approach has shown greater efficacy of tumor control, neurological outcome, and duration of response when compared with external beam radiotherapy, regardless of tumor histology. This study evaluates the efficacy of this treatment approach in a series of 57 consecutive patients.
METHODS: Patients treated for spinal metastases between 2007 and 2011 using the Varian Trilogy Linear Accelerator were identified retrospectively. Each received SRS, with or without initial surgical decompression and instrumentation. Medical records were reviewed to assess neurological outcome and surgical or radiation-induced complications. Magnetic resonance images were obtained for each patient at 3-month intervals posttreatment, and radiographic response was assessed as stability/regression or progression. End points were neurological outcome and local radiographic disease control at death or latest follow-up.
RESULTS: Fifty-seven patients with 69 lesions were treated with SRS for spinal metastases. Forty-eight cases (70%) were treated with SRS alone, and 21 (30%) were treated with surgery prior to SRS. A single fraction was delivered in 38 cases (55%), while a hypofractionated scheme was used in 31 (45%). The most common histological entities were renal cell, breast, and lung carcinomas. Radiographically, local disease was unchanged or regressed in 63 of 69 tumors (91.3%). Frankel score improved or remained stable in 68 of 69 cases (98.6%).
CONCLUSIONS: SRS, alone or as an adjunct following surgical decompression, provides durable local radiographic disease control while preserving or improving neurological function. This less-invasive alternative to radical spinal oncological resection appears to be effective regardless of tumor histology without sacrificing durability of radiographic or clinical response.

Related: Breast Cancer Kidney Cancer Lung Cancer

Arellano J, Hauber AB, Mohamed AF, et al.
Physicians' preferences for bone metastases drug therapy in the United States.
Value Health. 2015; 18(1):78-83 [PubMed] Related Publications
OBJECTIVE: Several characteristics of bone-targeted agents are considered when making treatment decisions. This study evaluated physicians' therapy preferences for preventing skeletal-related events (SREs) in patients with bone metastases secondary to solid tumors.
METHODS: A Web-enabled, discrete-choice experiment online survey was conducted among physicians who treated patients with bone metastases and solid tumors in the United States. Respondents chose between pairs of hypothetical medications defined by combinations of six attributes at varying levels for two hypothetical patients. Preference weights for attribute levels were estimated using a random-parameters logit model.
RESULTS: In total, 200 physicians completed the survey. Their mean age was 52 years, 57% were in practice for more than 15 years, 37% were oncologists, and 65% treated 10 or fewer patients with bone metastases weekly. Out-of-pocket cost to patients was the most important attribute overall. Among clinical outcomes, time to first SRE and risk of renal impairment were the most important attributes. Statistically significant preferences were observed for all attribute levels for time to first SRE, risk of renal impairment, and mode of administration. Predicted choice probability analysis showed that physicians preferred a hypothetical medication with attributes similar to those of denosumab over one with attributes similar to those of zoledronic acid.
CONCLUSIONS: Physicians indicated that clinical attributes are important when considering bone-targeting therapy for bone metastases, but consistent with the current health care landscape, patient out-of-pocket cost was the most important. With health care costs being increasingly shifted to patients, physicians require accurate information about co-pays and assistance programs to avoid patients receiving less costly, yet potentially inferior, treatment.

Related: USA

Menéndez RH, Erice SG, Bas CA, et al.
Spinal cord compression secondary to metastasis of malignant chondroid syringoma: case report.
J Neurosurg Spine. 2015; 22(3):310-3 [PubMed] Related Publications
The authors describe a case of spinal cord compression due to an epidural metastasis of malignant chondroid syringoma. Chondroid syringoma is a rare mixed tumor of the skin composed of both epithelial and mesenchymal elements. Although most are benign, malignant forms have been reported. Malignant chondroid syringoma may progress very slowly and the metastatic spread occurs late, appearing years after the original diagnosis. There is only one other report of spinal cord compression secondary to metastasis of malignant chondroid syringoma, which was finally diagnosed by microscopic examination of an autopsy specimen. This 63-year-old woman presented with a 4-week history of progressive paraparesis. Admission MRI of the thoracic spine showed an extradural mass arising from the posterior elements and left pedicle of T-9, which caused posterior compression of the spinal cord. Surgical decompression resulted in resolution of the neurological impairments. The histological results were consistent with metastasis of malignant chondroid syringoma. The patient underwent adjuvant radiotherapy and a favorable outcome was noted at the 2-year follow-up visit. This represents the first reported case of spinal cord compression from a metastasis of a malignant chondroid syringoma histologically confirmed in vivo. The authors' experience in this case suggests that resection followed by radiotherapy might be an acceptable means for achieving short-term, progression-free survival.

Morishige M, Muramatsu K, Tominaga Y, et al.
Surgical treatment of metastatic femoral fractures: achieving an improved quality of life for cancer patients.
Anticancer Res. 2015; 35(1):427-32 [PubMed] Related Publications
BACKGROUND: The femur is the most common long bone affected by metastatic carcinoma. We report our experience regarding treatment of metastatic femoral fracture using femoral head prosthesis (FHP) or intramedullary nailing (IM nail) with augmentation by polymethylmethacrylate (PMMA).
PATIENTS AND METHODS: Thirty-five complete fractures in 33 patients were treated surgically. Metastatic lesions were present in the femoral head to neck region (n=9), trochanteric to shaft region (n=23) and supracondular region (n=3).
RESULTS: Eight out of 9 patients with proximal femoral metastasis reconstructed by FHP were later able to walk outdoors. For the 11 patients with trochanteric metastasis, the short type of gamma nail was used for bony fixation. In two patients the inserted IM nails were broken. All other cases showed excellent clinical outcomes. For the 12 patients with femoral shaft metastasis, the long type of gamma nail was inserted. Nine cases showed excellent clinical outcomes without any serious complications.
CONCLUSION: FHP is indicated for metastases in the femoral head to neck region. IM nailing is best indicated when the lesion is located in the proximal to mid shaft and the patient's life expectancy is <6 month.

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Rutter CE, Yu JB, Wilson LD, Park HS
Assessment of national practice for palliative radiation therapy for bone metastases suggests marked underutilization of single-fraction regimens in the United States.
Int J Radiat Oncol Biol Phys. 2015; 91(3):548-55 [PubMed] Related Publications
PURPOSE: To characterize temporal trends in the application of various bone metastasis fractionations within the United States during the past decade, using the National Cancer Data Base; the primary aim was to determine whether clinical practice in the United States has changed over time to reflect the published randomized evidence and the growing movement for value-based treatment decisions.
PATIENTS AND METHODS: The National Cancer Data Base was used to identify patients treated to osseous metastases from breast, prostate, and lung cancer. Utilization of single-fraction versus multiple-fraction radiation therapy was compared according to demographic, disease-related, and health care system details.
RESULTS: We included 24,992 patients treated during the period 2005-2011 for bone metastases. Among patients treated to non-spinal/vertebral sites (n=9011), 4.7% received 8 Gy in 1 fraction, whereas 95.3% received multiple-fraction treatment. Over time the proportion of patients receiving a single fraction of 8 Gy increased (from 3.4% in 2005 to 7.5% in 2011). Numerous independent predictors of single-fraction treatment were identified, including older age, farther travel distance for treatment, academic treatment facility, and non-private health insurance (P<.05).
CONCLUSIONS: Single-fraction palliative radiation therapy regimens are significantly underutilized in current practice in the United States. Further efforts are needed to address this issue, such that evidence-based and cost-conscious care becomes more commonplace.

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Shabani M, Binesh F, Behniafard N, et al.
Clinicopathologic characteristics and survival of patients with bone metastasis in Yazd, Iran: a cross-sectional retrospective study.
Medicine (Baltimore). 2014; 93(28):e317 [PubMed] Related Publications
To evaluate the clinico-pathological and survival characteristics in patients with bone metastasis. This cross-sectional study was conducted on patients with bone metastasis who referred to Shahid Ramezanzadeh radiation oncology center. For all of the patients studied, demographic and survival information was recorded. SPSS was used to analyze the data. In this study, 89 men (53.3%) and 78 women (46.7%) with bone metastasis were examined. Most of the patients were in the 66 to 87 age range. Breast cancer was the most common type of cancer in women and prostate cancer was the commonest in men. In most patients, pain was the first manifestation of the disease, and the spine has been most frequently involved areas. The disease was diagnosed by isotope bone scan in the most cases. The mean survival was 31.1 months for patients with breast cancer, 12.9 months for patients with prostate cancer, 13.7 months for patients with lung cancer and the overall survival was 22.5. There was only a meaningful correlation between sex, type of cancer, radiation dose, and survival in patients. We found that age was more effective than the variable of cancer type in survival of patients with bone metastasis. The prognosis of patients with bone metastasis in our center is fair. There was a significant correlation between sex, type of cancer, radiation dose, and survival. Cox proportional hazards model showed that age was a predictor of death.

Related: Breast Cancer Lung Cancer Prostate Cancer

Iwase T, Yamamoto N, Ichihara H, et al.
The relationship between skeletal-related events and bone scan index for the treatment of bone metastasis with breast cancer patients.
Medicine (Baltimore). 2014; 93(28):e269 [PubMed] Related Publications
The aim of the present study was to investigate the relationships between the automated bone scan index (aBSI) and skeletal-related events (SRE) in breast cancer patients with bone metastasis. A computer-aided software (BONENAVI™) that was developed using an Artificial Neural Network (Artificial Neural Network) was used for the present analysis. Forty-five patients diagnosed with bone metastasis due to breast cancer from April 2005 through March 2013 were retrospectively analyzed. Before and after the time of initial treatment, aBSI, Artificial Neural Network score, and hotspot number were calculated, and the relationships between these scores and SRE were analyzed. Twenty cases showed decreased (improved) aBSI values after initial treatment (Group A), and 25 cases showed unchanged/increased (worsened) aBSI values (Group B). Chi-square analysis revealed a significant difference in incident numbers of SRE between the two groups--one case in Group A and 12 in Group B (P<0.001). Event-free survival was significantly shorter in Group B (hazard ratio: 8.31, 95% CI: 1.33-12.14, log-rank test; P<0.05). The groups were also divided by the results of 2 radiologists' visual scan interpretations, and no significant differences were shown in the number of SRE (P=0.82, P=0.10). When correlation analyses were performed between aBSI and bone metabolic or tumor markers, alkaline phosphatase was significantly correlated with aBSI at the time of initial treatment (R=0.69, P<0.05). In conclusion, aBSI is proposed as a useful and objective imaging biomarker in the detection of breast-cancer patients with bone metastasis at high risk of SRE.

Related: Breast Cancer

Young RJ, Khakoo Y, Yhu S, et al.
Extraneural metastases of medulloblastoma: desmoplastic variants may have prolonged survival.
Pediatr Blood Cancer. 2015; 62(4):611-5 [PubMed] Related Publications
BACKGROUND: Extraneural metastases from CNS medulloblastoma are rare and poorly described. The purpose of this study is to describe the clinical and radiological characteristics of a large single institution series of patients with medulloblastoma who developed extraneural metastases.
PROCEDURE: We retrospectively reviewed a departmental database over a 20 year period for all patients with medulloblastoma who developed extraneural metastases. Chart and imaging reviews were performed, and overall survival (OS) estimated by the Kaplan-Meier method.
RESULTS: We found 14 patients with medulloblastoma and extraneural metastases. The median age at initial diagnosis was 16.3 years (range, 3.2-44.2), and the most common subtype was desmoplastic (n = 6, 42.9%). After initial gross total resection, most patients received radiation therapy alone (n = 10, 71.4%). Metastases to bone were most common (n = 11, 78.6%) followed by metastases to bone marrow (n = 6, 42.9%), usually to the spine. The median time from initial diagnosis to first extraneural metastasis was 1.5 years (range, 0.2-17.4), and the median OS from extraneural metastasis to death was 3.3 years (range, 0-18). The Kaplan-Meier estimate of 5 year OS from extraneural metastasis diagnosis was 40.0% (95% CI, 20.2-79.2).
CONCLUSIONS: Extraneural metastases from medulloblastoma may rarely develop after initial diagnosis to involve bone and bone marrow. We found that desmoplastic variant extraneural tumors had longer survival than nondesmoplastic variants, suggesting that histopathological and more recent molecular subtyping have important roles in determining the prognosis of medulloblastoma patients.

Related: Childhood Medulloblastoma / PNET Medulloblastoma

Maroni P, Matteucci E, Drago L, et al.
Hypoxia induced E-cadherin involving regulators of Hippo pathway due to HIF-1α stabilization/nuclear translocation in bone metastasis from breast carcinoma.
Exp Cell Res. 2015; 330(2):287-99 [PubMed] Related Publications
The present study deals with the molecular mechanisms involved in the regulation of E-cadherin expression under hypoxia, because the adjustment of the amount of E-cadherin due to physical stimuli of the microenvironment might influence the colonization of metastasis to skeleton. We analyzed the effect of 1% oxygen tension, that is similar to that encountered in the bone marrow by metastatic cells spreading from breast carcinoma. The purpose was to evaluate the hypoxia-orchestrated control of E-cadherin transactivation via hypoxia inducible factor-1 (HIF-1) and peroxisome proliferator activated receptor-γ (PPARγ), and the involvement of Hippo pathway members, as regulators of transcription factors. To give a translational significance to the study, we took into consideration human pair-matched ductal breast carcinoma and bone metastasis: E-cadherin and Wwox were expressed in bone metastasis but not in breast carcinoma, while HIF-1α and TAZ seemed localized principally in nuclei of metastasis and were found in all cell compartments of breast carcinoma. A close examination of the regulatory mechanisms underlying E-cadherin expression in bone metastasis was done in 1833 clone derived from MDA-MB231 cells. Hypoxia induced E-cadherin only in 1833 clone, but not in parental cells, through HIF-1 and PPARγ activities, while Wwox decreased. Since Wwox was highly expressed in bone metastasis, the effect of ectopic Wwox was evaluated, and we showed E-cadherin transactivation and enhanced invasiveness in WWOX transfected 1833 cells. Also, hypoxia was additive with ectopic Wwox remarkably enhancing HIF-1α nuclear shuttle and accumulation due to the lengthening of the half-life of HIF-1α protein; under this experimental condition HIF-1α appeared as a slower migrated band compared with control, in agreement with the phosphorylation state. The in vitro data strongly supported the almost exclusive presence of HIF-1α in nuclei of human-bone metastasis. Thus, we identified Wwox as a novel molecule in the HIF-1α-HDM2 regulatory loop, necessary for the dynamic regulation of the HIF-1α amount, and we suggested that the reduction of endogenous Wwox free pool under hypoxia might also be due to the interaction with HDM2, sequestering the E3 ubiquitin ligase. We highlighted the importance of nuclear HIF-1α in the biology of metastasis for the mesenchymal-epithelial transition: this phenotype was regulated by Wwox plus hypoxia through E-cadherin target gene, playing a pivotal role in bone metastasis colonization.

Related: Breast Cancer HIF1A PPARG gene MDM2 gene WWOX

Kotecha R, Angelov L, Barnett GH, et al.
Calvarial and skull base metastases: expanding the clinical utility of Gamma Knife surgery.
J Neurosurg. 2014; 121 Suppl:91-101 [PubMed] Related Publications
OBJECT: Traditionally, the treatment of choice for patients with metastases to the calvaria or skull base has been conventional radiation therapy. Because patients with systemic malignancies are also at risk for intracranial metastases, the utility of Gamma Knife surgery (GKS) for these patients has been explored to reduce excess radiation exposure to the perilesional brain parenchyma. The purpose of this study was to report the efficacy of GKS for the treatment of calvarial metastases and skull base lesions.
METHODS: The authors performed a retrospective chart review of 21 patients with at least 1 calvarial or skull base metastatic lesion treated with GKS during 2001-2013. For 7 calvarial lesions, a novel technique, in which a bolus was placed over the treatment site, was used. For determination of local control or disease progression, radiation therapy data were examined and posttreatment MR images and oncology records were reviewed. Survival times from the date of procedure were estimated by using Kaplan-Meier analyses.
RESULTS: The median patient age at treatment was 57 years (range 29-84 years). A total of 19 (90%) patients received treatment for single lesions, 1 patient received treatment for 3 lesions, and 1 patient received treatment for 4 lesions. The most common primary tumor was breast cancer (24% of patients). Per lesion, the median clinical and radiographic follow-up times were 10.3 months (range 0-71.9 months) and 7.1 months (range 0-61.3 months), respectively. Of the 26 lesions analyzed, 14 (54%) were located in calvarial bones and 12 (46%) were located in the skull base. The median lesion volume was 5.3 cm(3) (range 0.3-55.6 cm(3)), and the median prescription margin dose was 15 Gy (range 13-24 Gy). The median overall survival time for all patients was 35.9 months, and the 1-year local control rate was 88.9% (95% CI 74.4%-100%). Local control rates did not differ between lesions treated with the bolus technique and those treated with traditional methods or between calvarial lesions and skull base lesions (p > 0.05). Of the 3 patients for whom local treatment failed, 1 patient received no further treatment and 2 patients responded to salvage chemotherapy. Subsequent brain parenchymal metastases developed in 2 patients, who then underwent GKS.
CONCLUSIONS: GKS is an effective treatment modality for patients with metastases to the calvarial bones or skull base. For patients with superficial calvarial lesions, a novel approach with bolus application resulted in excellent rates of local control. GKS provides an effective therapeutic alternative to conventional radiation therapy and should be considered for patients at risk for calvarial metastases and brain parenchymal metastases.

Related: Breast Cancer Kidney Cancer Lung Cancer

Carter RZ, Micocci KC, Natoli A, et al.
Tumour but not stromal expression of β3 integrin is essential, and is required early, for spontaneous dissemination of bone-metastatic breast cancer.
J Pathol. 2015; 235(5):760-72 [PubMed] Related Publications
Although many preclinical studies have implicated β3 integrin receptors (αvβ3 and αIIbβ3) in cancer progression, β3 inhibitors have shown only modest efficacy in patients with advanced solid tumours. The limited efficacy of β3 inhibitors in patients could arise from our incomplete understanding of the precise function of β3 integrin and, consequently, inappropriate clinical application. Data from animal studies are conflicting and indicate heterogeneity with respect to the relative contributions of β3-expressing tumour and stromal cell populations in different cancers. Here we aimed to clarify the function and relative contributions to metastasis of tumour versus stromal β3 integrin in clinically relevant models of spontaneous breast cancer metastasis, with particular emphasis on bone metastasis. We show that stable down-regulation of tumour β3 integrin dramatically impairs spontaneous (but not experimental) metastasis to bone and lung without affecting primary tumour growth in the mammary gland. Unexpectedly, and in contrast to subcutaneous tumours, orthotopic tumour vascularity, growth and spontaneous metastasis were not altered in mice null for β3 integrin. Tumour β3 integrin promoted migration, protease expression and trans-endothelial migration in vitro and increased vascular dissemination in vivo, but was not necessary for bone colonization in experimental metastasis assays. We conclude that tumour, rather than stromal, β3 expression is essential and is required early for efficient spontaneous breast cancer metastasis to bone and soft tissues. Accordingly, differential gene expression analysis in cohorts of breast cancer patients showed a strong association between high β3 expression, early metastasis and shorter disease-free survival in patients with oestrogen receptor-negative tumours. We propose that β3 inhibitors may be more efficacious if used in a neoadjuvant setting, rather than after metastases are established.

Related: Breast Cancer Signal Transduction

Xin G, Du J, Xu Y
Isolated sacral metastases as the initial presentation from an endometroid ovarian carcinoma: a case report.
Eur J Gynaecol Oncol. 2014; 35(5):589-91 [PubMed] Related Publications
Bone metastases are rarely in ovarian carcainoma. It usually occurrs only when the cancer is advanced or recurrent. A case of endometrioid carcinoma in right ovary with intact capsule is reported. The isolated sacral metastasis was found as the initial presentation, and no distant metastases were reported.

Related: Ovarian Cancer

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