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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Obuchowska I, Pawluczuk B, Mariak Z Exophthalmos as a first manifestation of the systemic spread of small cell lung cancer. Klin Oczna. 2013; 115(2):135-40 [PubMed] Related Publications
Small cell lung cancer is characterized by rapid growth and early metastases. The most frequent locations of the secondary lesions include adrenal glands, brain, liver, and skeleton. On initial diagnosis, up to 70% of patients with small cell lung cancer have metastases. Metastases to the eye or orbit developed approximately 0.7-12% of patients with lung cancer. Clinical signs and symptoms of orbital metastases may include exophthalmos, diplopia, pain, limited ocular motility, blurred vision, swollen eyelid, conjunctival hyperemia and edema, increased ocular pressure and papilledema. Here, we report a rare case of exophthalmos as the first manifestation of a metastatic tumor of orbit due to small cell lung cancer.
Chen CY, Huang KG, Abdullah NA, et al. Successful treatment of isolated fibular bone metastasis in a uterine endometrial cancer of clear cell carcinoma. Eur J Gynaecol Oncol. 2013; 34(4):347-9 [PubMed] Related Publications
Clear cell carcinoma of the endometrium is an uncommon histological subtype and isolated metastasis to bone is rare. The authors present a case of a 61-year-old woman who underwent laparoscopic staging surgery for clear cell carcinoma of uterine endometrium (FIGO Stage IB) and early recurrence with isolated fibular bone metastasis three months later. With salvage radiotherapy (RT), she remains disease-free after 46 months. Curative-intended treatment with RT is possible as in this case.
Zhang XH, Jin X, Malladi S, et al. Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell. 2013; 154(5):1060-73 [PubMed] Related Publications
How organ-specific metastatic traits arise in primary tumors remains unknown. Here, we show a role of the breast tumor stroma in selecting cancer cells that are primed for metastasis in bone. Cancer-associated fibroblasts (CAFs) in triple-negative (TN) breast tumors skew heterogeneous cancer cell populations toward a predominance of clones that thrive on the CAF-derived factors CXCL12 and IGF1. Limiting concentrations of these factors select for cancer cells with high Src activity, a known clinical predictor of bone relapse and an enhancer of PI3K-Akt pathway activation by CXCL12 and IGF1. Carcinoma clones selected in this manner are primed for metastasis in the CXCL12-rich microenvironment of the bone marrow. The evidence suggests that stromal signals resembling those of a distant organ select for cancer cells that are primed for metastasis in that organ, thus illuminating the evolution of metastatic traits in a primary tumor and its distant metastases.
In order to establish themselves in distal sites, metastatic cancer cells need to acquire organ-specific traits. Zhang et al. provide evidence in breast cancer that a tumor cell's acquisition of properties for successful bone metastasis is influenced by signals from the stroma of the primary tumor.
Metastatic spread to the oral cavity of a malignant neoplasm is a rare yet important sign of advanced systemic malignant disease. This manuscript briefly describes the metastatic process and highlights the most common neoplasms that metastasise to the oral cavity as well as their clinical and radiological presentations. The role of the patients' history in suspecting metastatic disease and the importance of a microscopic diagnosis is emphasised.
Wang DC, Wang HF, Yuan ZN Runx2 induces bone osteolysis by transcriptional suppression of TSSC1. Biochem Biophys Res Commun. 2013; 438(4):635-9 [PubMed] Related Publications
Advanced breast cancers frequently metastasize to bone, resulting in osteolytic lesions, however, the underlying mechanisms are poorly understood. Runx2, a bone-specific transcriptional factor, is abnormally expressed in highly metastatic breast cancer cells. Here, we found that TSSC1 inhibits breast cancer cell invasion. Subsequently, TSSC1 is confirmed as a target of Runx2 and is negatively regulated by Runx2. Furthermore, overexpression of Runx2 induces bone osteolysis in a TSSC1-dependent manner. Our results may provide a strategy for the treatment of breast cancer and the prevention of skeletal metastasis.
Singh G, Lim CT, Jonathan TJ, Nathan SS Evaluation of the role and cost-effectiveness of end-of-life orthopaedic interventions in cancer patients with skeletal metastases to the hip. J Palliat Care. 2013; 29(2):83-90 [PubMed] Related Publications
This study aimed to evaluate the effect of hip reconstruction on patients with skeletal metastases to the hip. We investigated the effect of hip reconstruction on quality of life and ambulatory status, as well as cost-effectiveness of hip reconstruction in this group of patients.
Wang JM, Li X A 78-year-old man with rapidly-progressing sarcomatoid renal cell carcinoma. Conn Med. 2013 Jun-Jul; 77(6):343-6 [PubMed] Related Publications
We report a case of metastatic sarcomatoid renal cell carcinoma (SRCC), which presented as nephrotic syndrome with diffuse peripheral edema. At the time of diagnosis, the metastatic disease involved bone, with peritoneal lymphadenopathy. The nephrotic syndrome did not improve after nephrectomy. Systemic disease progressed quickly postoperatively. The sarcomatoid renal cell carcinoma in this case had an aggressive clinical course. CNS metastasis quickly developed, and the patient passed away soon after.
Nagata M, Kudoh S, Mitsuoka S, et al. Skeletal-related events in advanced lung adenocarcinoma patients evaluated EGFR mutations. Osaka City Med J. 2013; 59(1):45-52 [PubMed] Related Publications
BACKGROUND: The rate of lung cancer metastasis to the bone is high and skeletal-related events (SREs) decrease the quality of life in many patients. Recently, it was found that a subgroup of patients with non-small cell lung cancer (NSCLC) have specific mutations in the EGFR (epidermal growth factor receptor) gene. We assessed the SREs in advanced lung adenocarcinoma patients that evaluated EGFR mutations in whom bone metastasis was present. METHODS: We retrospectively investigated the clinical records of 377 patients with advanced NSCLC. Patients were evaluated for the presence of EGFR mutations, bone metastases, the incidence of SREs, and treatment history before the first SRE. RESULTS: A total of 78 patients who were evaluated for EGFR mutations had bone metastasis from lung adenocarcinoma. The most frequent site of bone metastasis was the spine (36.2%). SREs occurred in 37 patients (47.4%), the most common of which was bone radiotherapy (41.0%). Significant differences were not observed in the sites of bone metastases or the patterns of SREs between patients with and without EGFR mutations. The median time from bone metastasis to the first SRE was 5.8 months in all of the subjects, history of EGFR-tyrosine kinase inhibitor (TKI) treatment was significantly associated with longer median time to first SRE (14.2 months vs 1.3 months, p < 0.0001), and the median time to first SRE of patients with PS 0-1 was longer (8.5 months vs 0.9 months, p = 0.0023). CONCLUSIONS: We found that SRE patterns have no difference between EGFR mutation positive and negative, and that the time from bone metastasis to the first SRE was longer in advanced lung adenocarcinoma patients with good PS and history of EGFR-TKI treatment.
Galasso O, Gasparini G, Mariconda M, Signorelli F Isolate metastasis of listhetic vertebra. J Back Musculoskelet Rehabil. 2013; 26(3):255-9 [PubMed] Related Publications
STUDY DESIGN: Case report. OBJECTIVE: To document the case of isolated metastasis in an isthmic spondylolisthesis in the adult. SUMMARY OF BACKGROUND DATA: The progression of isthmic spondylolisthesis occurs infrequently in the adult. Previous reports have pointed out the pathogenic responsibility of the progressive disc collapse. METHODS: A 58-year-old woman was evaluated for severe back and bilateral leg pain. Standing radiographs of her lumbar spine showed L5-S1 spondylolisthesis. CT and MRI scans demonstrated a tumor infiltration of the L5 listhetic vertebra. RESULTS: Bilateral interruption of the posterior arch was noted at surgery. A posterior decompression with an L3-S1 pedicle screw fixation was performed without complication. Leg pain and paraparesis promptly regressed. A solitary localization of an undifferentiated adenocarcinoma of unknown origin was diagnosed. The patient refused further surgery and died three years after the operation. CONCLUSIONS: The progression of isthmic spondylolisthesis occurs infrequently in the adult. This case shows that tumor infiltration is a potential cause for the onset/progression of spondylolisthesis in the adult. An MRI or CT scan of the spine is recommended in skeletally mature patients with isthmic spondylolisthesis who sustain severe and acute exacerbation of their back pain.
Sawant A, Ponnazhagan S Myeloid-derived suppressor cells as osteoclast progenitors: a novel target for controlling osteolytic bone metastasis. Cancer Res. 2013; 73(15):4606-10 [PubMed] Article available free on PMC after 01/08/2014 Related Publications
Blume C, von Lehe M, van Landeghem F, et al. Extracranial glioblastoma with synchronous metastases in the lung, pulmonary lymph nodes, vertebrae, cervical muscles and epidural space in a young patient - case report and review of literature. BMC Res Notes. 2013; 6:290 [PubMed] Article available free on PMC after 01/08/2014 Related Publications
BACKGROUND: Extraneural and extracranial metastases of glioblastoma (GB) are very rarely reported in the literature. They occur in only 0.2% of all GB patients. CASE PRESENTATION: We present a 40 year old caucasian male with secondary GB and first diagnosis of an astrocytoma world health organisation (WHO) grade II through stereotactic biopsy in 2006. He presented a new hemiparesis and a progress of the known mass lesion in 2008. Subtotal tumor resection was performed and the histological examination verified a GB. After combined radio- and chemotherapy the adjuvant temozolomide therapy was not started because of non-compliance. In 2011 a second local relapse was resected and 4 month later the patient presented a fast progressing tetraparesis. Cervical CT and MRI scan showed a mass lesion infiltrating the fifth and sixth vertebra with infiltration of the spinal canal and large paravertebral tumor masses. Emergency surgery was performed. By additional screening further metastases were detected in the thoracal and lumbal spine and surprisingly also in the lung and pulmonary lymphnodes. Palliative radio- and chemotherapy of the pulmonal lesions was completed, further antitumor therapy was rejected. The patient died 10 months after diagnosis of the extraneural metastases. CONCLUSION: Especially young "long-term-survivors" seem to have a higher risk of extraneural metastasis from a GB and appropriate staging should be performed in these cases.
Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013; 369(3):213-23 [PubMed] Related Publications
BACKGROUND: Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. METHODS: In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. RESULTS: At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. CONCLUSIONS: In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).
Qiu ZL, Wu CG, Zhu RS, et al. Unusual case of solitary functioning bone metastasis from a "parathyroid adenoma": imagiologic diagnosis and treatment with percutaneous vertebroplasty--case report and literature review. J Clin Endocrinol Metab. 2013; 98(9):3555-61 [PubMed] Related Publications
BACKGROUND: Parathyroid carcinoma is a rare endocrine malignancy that accounts for a small percentage of patients with primary hyperparathyroidism. Here, an unusual patient with parathyroid carcinoma misdiagnosed as a parathyroid adenoma was reported. A solitary L4 vertebral metastasis, which was localized by technetium-99m-labelled methoxyisobutyl isonitrile ((99m)Tc-MIBI) single photon emission computed tomography (SPECT)/computed tomography (CT) fusing images, was successfully treated with percutaneous vertebroplasty (PVP) for the first time. PATIENT AND METHODS: A 53-year-old man with primary hyperparathyroidism and a palpable mass in the right neck was referred. A right unilateral parathyroidectomy was performed. A pathological diagnosis of parathyroid adenoma was made; however, hyperparathyroidism persisted with a serum calcium of 4.51 mmol/L and a PTH of 3235 pg/mL. Early and delayed images of the (99m)Tc-MIBI whole-body scan revealed abnormal (99m)Tc-uptake in the lower abdomen. The delayed (99m)Tc-MIBI SPECT/CT fusion images found that the lower abnormal (99m)Tc-MIBI uptake was located in the area of osteolytic destruction of the L4 vertebra. A bone metastasis from parathyroid carcinoma was diagnosed based on histopathological evaluation and immunohistochemical staining. PVP was performed to treat the osteolytic destruction of the L4 vertebra. The PTH level decreased to normal within 1 week after PVP. CONCLUSION: (99m)Tc-MIBI SPECT/CT scan may be a useful and suitable method by which to localize functioning distant metastases from the parathyroid cancer when serum PTH and calcium levels remain greatly elevated after parathyroidectomy. PVP may be an effective procedure in eliminating cancer cells, reducing serum PTH levels, preventing bone fractures, and improving the quality of life of patients.
Zheng W, Wu J, Xiao JR, Guo Q Survival and health-related quality of life in patients with spinal metastases originated from primary hepatocellular carcinoma. J Evid Based Med. 2013; 6(2):81-9 [PubMed] Related Publications
BACKGROUND: In recent years, there have been more and more clinical trails focused on patient-reported outcomes (PRO), especially in the assessment of quality of life (QOL). Previous report on QOL assessment on patients with spinal metastases from primary hepatocellular carcinoma (HCC) is rare. And there is no standard treatment for those patients. OBJECTIVE: The purpose of the current study is to determine whether spinal surgery could improve QOL in HCC patients with spinal metastases and prolong their survival. METHODS: We conducted a single-center, non-randomized, prospective, longitudinal study in two groups: surgery group and non-surgery group. When diagnosed, all eligible patients completed a baseline QOL assessment using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. All patients' quality of life was subsequently assessed again at another 4 time points: 1, 3, 6 and 9 months after diagnosis. RESULTS: From July 1, 2007 to March 31, 2009, we identified 62 patients (surgery group n = 29, non-surgery group n = 33) who were eligible for the observational study. Only 21 patients in the surgery group and 22 patients in the non-surgery group survived more than 9 months and completed all 5 follow-up QOL assessments. The median survival time was 12.6 months in the surgery group and 13.7 months in the non-surgery group (P = 0.530). The results suggested that whether in the surgery or non-surgery group, QOL scores in 9-month period after diagnosis decreased in the same mode, and surgical treatment for spinal metastases could improve neither patients' QOL nor survival. CONCLUSION: Spinal surgery could not provide benefits for patients with spinal metastases from HCC in QOL or survival. We do not recommend surgical treatment for patients with metastases from HCC to the spine.
Ahmadnia H, Amirmajdi NM, Mansourian E Renal cell carcinoma presenting as mandibular metastasis. Saudi J Kidney Dis Transpl. 2013; 24(4):789-92 [PubMed] Related Publications
Renal clear cell carcinoma (RCC) has different manifestations, including uncommon metastasis and paraneoplastic syndromes. Here we report a rare case of RCC presenting as metastasis to the mandible. A 57-year-old patient with mandibular swelling was referred to the dentist. After necessary evaluations, an incisional biopsy of mandible showed metastatic RCC. The patient was referred to the urologist. The patient underwent right radical nephrectomy. Pathological examination showed clear renal cell carcinoma. Every abnormal bone lesion in the oral cavity should be evaluated carefully and the possibility of a malignant lesion should always be considered.
D'Amico L, Patanè S, Grange C, et al. Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature. Br J Cancer. 2013; 108(12):2525-36 [PubMed] Article available free on PMC after 25/06/2014 Related Publications
BACKGROUND: Bone metastases represent a common and severe complication in breast cancer, and the involvement of cancer stem cells (CSCs) in the promotion of bone metastasis is currently under discussion. Here, we used a human-in-mice model to study bone metastasis formation due to primary breast CSCs-like colonisation. METHODS: Primary CD44⁺CD24⁻ breast CSCs-like were transduced by a luciferase-lentiviral vector and injected through subcutaneous and intracardiac (IC) routes in non-obese/severe-combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The CSCs-like localisation was monitored by in vivo luciferase imaging. Bone metastatic CSCs-like were analysed through immunohistochemistry and flow cytometry, and gene expression analyses were performed by microarray techniques. RESULTS: Breast CSCs-like colonised the human-implanted bone, resulting in bone remodelling. Bone metastatic lesions were histologically apparent by tumour cell expression of epithelial markers and vimentin. The bone-isolated CSCs-like were CD44⁻CD24⁺ and showed tumorigenic abilities after injection in secondary mice. CD44⁻CD24⁺ CSCs-like displayed a distinct bone tropism signature that was enriched in genes that discriminate bone metastases of breast cancer from metastases at other organs. CONCLUSION: Breast CSCs-like promote bone metastasis and display a CSCs-like bone tropism signature. This signature has clinical prognostic relevance, because it efficiently discriminates osteotropic breast cancers from tumour metastases at other sites.
Murillo J, Bagan JV, Hens E, et al. Tumors metastasizing to the oral cavity: a study of 16 cases. J Oral Maxillofac Surg. 2013; 71(9):1545-51 [PubMed] Related Publications
PURPOSE: An analysis was performed of the clinical and epidemiologic characteristics of a group of patients diagnosed with oral metastases of distant primary tumors or unknown primary malignancies. MATERIAL AND METHODS: The study series consisted of 16 patients with oral metastatic lesions seen in the Department of Stomatology and Maxillofacial Surgery, Valencia University General Hospital (Valencia, Spain) that had been diagnosed in the previous 15 years. A retrospective analysis was made of patient age and gender, clinical characteristics of metastatic lesions, location of the primary tumor, and time elapsed from diagnosis to the death of a patient. RESULTS: There were 13 male and 3 female patients (mean age, 58.8 years). Ten patients had been diagnosed previously and were being treated for a primary tumor; 2 patients were diagnosed with a primary malignancy in the department; and 4 patients presented with an unidentified primary tumor (metastatic disease diagnosed from biopsy study). The predominant clinical presentation was mixed soft tissue and bone metastases followed by solely soft tissue lesions and solely bone lesions. Some patients showed no apparent oral lesions. Primary malignancies originated mainly from the lung followed by the prostate, gastrointestinal tract, thyroid gland, breast, and liver. Mean survival from diagnosis of oral metastases was 8.25 months. CONCLUSION: Oral metastatic lesions are infrequent, can affect male and female patients equally, can manifest at any age, and may constitute the first manifestation of a still unidentified primary malignancy. According to the literature, bone metastases are more common than soft tissue metastases. Nevertheless, in the present series, there was a clear male predominance, and the oral metastases showed a predominance of mixed presentations followed by solely soft tissue lesions and solely bone metastases.
Jamal-Hanjani M, Karpathakis A, Kwan A, et al. Bone metastases in germ cell tumours: lessons learnt from a large retrospective study. BJU Int. 2013; 112(2):176-81 [PubMed] Related Publications
OBJECTIVE: To determine the characteristics of patients with germ cell cancer and bone metastases. PATIENTS AND METHODS: The case records of patients with known germ cell tumours (GCTs) within the Anglian Germ Cell Cancer Group database between January 2005 and March 2011 were reviewed retrospectively. Data were collected for histopathology, presence of bone metastases at diagnosis or relapse, site of bone metastases and imaging method used to confirm bone metastases, treatment received, response to treatment and overall survival. We present here the largest unselected cohort of bone metastases in patients with GCTs. RESULTS: In all, 2550 cases of GCTs were reviewed and there was bone involvement in 19 cases. The primary site was either testicular (13/19), mediastinal (1/19) or unknown (5/19). Most cases were non-seminomatous GCTs (11/19, 58%) and only three cases of seminomatous GCTs (3/19, 16%) with five cases in which diagnosis was based on clinical history and significantly raised GCT markers (5/19, 26%). In all of these five cases β-human chorionic gonadotrophin was raised and in three α-fetoprotein was raised, consistent with non-seminomatous GCT. There were bone metastases at diagnosis (0.51%, 13/2550) or at relapse (0.24%, 6/2550). The sites of bone metastases were the vertebrae (15/19, 79%), pelvis (3/19, 16%), ribs (3/19, 16%) and femur (2/19, 11%). Ten patients (53%) had solitary, and nine patients (47%) had multiple, sites of bone metastases. In patients presenting with bone metastases at diagnosis compared with relapse, the mortality rate was 23% (3/13) and 50% (3/6), respectively. After receiving one line of chemotherapy, nine patients (47%) remained in remission not requiring further treatment, six (32%) required further chemotherapy due to subsequent relapse, three (16%) died after first-line chemotherapy and one was lost to follow-up. At the time of data collection and based on the last clinic follow-up, six patients (32%) had died with a median (interquartile range, IQR) follow-up of 11.5 (4.3, 24.8) months and 10 (53%) remained alive with a median (IQR) follow-up of 26 (13.5, 48) months Three patients were lost to follow-up. Of the known patients alive, eight (42%) remained in remission and two (11%) had recurrent disease requiring further treatment. CONCLUSION: Although bone disease in germ cell cancer is rare, awareness of this condition is important and there is a need for prospective evaluation of patient characteristics, treatment approaches and survival outcome in this group of patients.
Calderón Alicea E, Santiago-Casiano M, Cáceres-Perkins W, Almodovar A Metastatic lymphoepithelioma to the orbit: an aggressive rare nasopharygeal tumor in a Hispanic patient. Bol Asoc Med P R. 2012 Sep-Dec; 104(4):37-40 [PubMed] Related Publications
A 64 year-old Hispanic male patient presented to our institution with a three-month history of frontal headaches, reduced vision, retroorbital pain, photophobia, sinus congestion, bloody nasal discharge, and decreased audition in the left ear. The diagnosis of metastatic lymphoepithelioma to the orbit was made based on clinical history, histopathological examination of an orbital biopsy, and imaging studies. Lymphoepithelioma rarely develops in Hispanic populations. However, it is endemic in certain areas, including North Africa, Southeast Asia. China and the far north hemisphere. Radiotherapy is th treatment of choice of localized lymphoepithelioma and concurrent chemotherapy-radiotherapy with neoadjuvant chemotherapy has been used in locally advanced metastatic settings.
Müller K, Schlamann A, Seidel C, et al. Craniospinal irradiation with concurrent temozolomide and nimotuzumab in a child with primary metastatic diffuse intrinsic pontine glioma. A compassionate use treatment. Strahlenther Onkol. 2013; 189(8):693-6 [PubMed] Related Publications
Primary metastatic diffuse intrinsic pontine glioma (DIPG) is relatively rare and associated with a dismal prognosis. Combining craniospinal irradiation (CSI) with concurrent temozolomide and nimotuzumab therapy may slightly improve tumor control and overall survival. However, little is known about the feasibility and toxicity of this treatment approach. Here, we describe the case of an 8-year-old girl with primary metastatic DIPG who received craniospinal radiotherapy, a local boost, and concurrent temozolomide and nimotuzumab treatment based on an individual therapy recommendation. Radiotherapy could be completed without any interruption. However, concurrent temozolomide had to be disrupted several times due to considerable acute myelotoxicity (grade III-IV).Maintenance immunochemotherapy could be started with a delay of 5 days and was performed according to treatment schedule. The disease could be stabilized for a few months. A routine MRI scan finally depicted disease progression 5.7 months after the start of irradiation. The patient died 1.9 months later.
Farrell C Bone metastases: assessment, management and treatment options. Br J Nurs. 2013 May 23-Jun 12; 22(10):S4, S6, S8-11 [PubMed] Related Publications
Cancer cells from a primary tumour can spread to other parts of the body through the bloodstream or the lymphatic system. Bone metastases are common in multiple myeloma, where 70-80% of patients have bone metastases at diagnosis. They are also a common feature in solid tumours such as breast, lung, prostate, thyroid and renal carcinomas. The median survival in patients with bone metastases from breast cancer is 24 months; 20% of patients survive for 5 years or more. Pain is the most common symptom of bone metastases, which can often be severe and difficult to control. This article will discuss normal bone physiology and explain the changes that occur when cancer cells spread to bone. It will outline the signs and symptoms of bone metastases and discuss patient assessment, symptom management and treatment options, including different bisphosphonates. The physical and psychological impact of bone metastases should not be underestimated and nurses are well placed to improve the quality of life of patients.
Li AM, Tian AX, Zhang RX, et al. Protocadherin-7 induces bone metastasis of breast cancer. Biochem Biophys Res Commun. 2013; 436(3):486-90 [PubMed] Related Publications
Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer.
Lumachi F, Santeufemia DA, Del Conte A, et al. Carboxy-terminal telopeptide (CTX) and amino-terminal propeptide (PINP) of type I collagen as markers of bone metastases in patients with non-small cell lung cancer. Anticancer Res. 2013; 33(6):2593-6 [PubMed] Related Publications
The early diagnosis of non-small cell lung carcinoma (NSCLC) is difficult, and 30-40% of patients with NSCLC develop bone metastases (BMs) during the course of their disease. Because the delayed demonstration of skeletal involvement may seriously affect survival, there is a need for early diagnosis of BMs. Unfortunately, the sensitivity of common serum tumor markers is low and they are used mainly for monitoring the efficacy of therapy and detection of recurrence. The aim of this study was to evaluate the utility of a panel of serum biomarkers in patients with NSCLC and BMs. Sixteen patients (11 males, 5 females; median age=64 years, range 54-68 years) with NSCLC and BMs (cases), and 18 age- and stage-matched patients without BMs (controls) underwent measurement of serum carboxy-terminal telopeptide of type I collagen (CTX), tartrate-resistant acid phosphatase isoform type 5b (TRAP5b) and amino-terminal propeptide of type I collagen (PINP), carcinoembryonic antigen (CEA) and fragments of cytokeratin 19 (CYFRA 21-1. CTX (443.7 ± 945.1 vs. 402.7 ± 28.4 pg/ml, p=0.003) and PINP (75.9 ± 11.4 vs. 64.1 ± 7.5 μg/l, p=0.001) were significantly higher in patients with BMs, while the mean value of the other markers did not differ (p=NS) between cases and controls. The sensitivity, specificity and accuracy were 73.3%, 86.7% and 79.4% for CTX; 55.5%, 62.5% and 58.8% for CEA; 65.0%, 78.6% and 70.6% for CYFRA; 30.4%, 76.2% and 67.6% for TRAP5b; and 72.2%, 81.2% and 76.5% for PINP, respectively. The area under the receiver operating characteristic curve (AUC) for CTX was 0.68. In conclusion, CTX and PINP measurement can be useful in monitoring patients with NSCLC during follow-up, with the aim of detecting BMs early.
de la Piedra C, Alcaraz A, Bellmunt J, et al. Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study. Br J Cancer. 2013; 108(12):2565-72 [PubMed] Article available free on PMC after 25/06/2014 Related Publications
BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (β-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with β-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, β-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.
Lee JH, Stein M, Roychowdhury S Percutaneous treatment of a sacral metastasis with combined embolization, cryoablation, alcohol ablation and sacroplasty for local tumor and pain control. Interv Neuroradiol. 2013; 19(2):250-3 [PubMed] Article available free on PMC after 01/06/2014 Related Publications
Multiple treatment options have been introduced for the treatment of sacral tumoral bone pain. These options include pre-operative sacral embolization, percutaneous cryoablation, alcohol ablation, and sacroplasty. We intend to show that in the correct clinical scenario, a combination of the four procedures performed as a two-stage process can effectively treat tumoral bone pain refractory to medical therapy.
Uccella S, Morris JM, Bakkum-Gamez JN, et al. Bone metastases in endometrial cancer: report on 19 patients and review of the medical literature. Gynecol Oncol. 2013; 130(3):474-82 [PubMed] Related Publications
OBJECTIVE: Because few cases of bone metastases of endometrial cancer have been reported, and information is scarce on their incidence, treatment, prognosis, and outcomes, we sought to compile a series of bone metastases of endometrial cancer and to systematically review the medical literature. METHODS: We retrospectively reviewed medical records of patients who had osseous metastases of endometrial cancer treated initially at Mayo Clinic (1984-2001), and of all patients who were referred for treatment of primary bone metastases after primary treatment for endometrial cancer elsewhere. RESULTS: Of 1632 patients with endometrial cancer, 13 (0.8%) had primary bone dissemination and 6 (0.4%) were referred after initial treatment. Three (15.8%) of these 19 had bone metastases at presentation; in the rest, median time to recurrence was 19.5 months (range, 3-114). The most common sites were the spine and hip. Median survival after metastasis was 12 months (range, 2-267). Median survival after radiotherapy alone vs. multimodal treatment was 20 months (range, 12-119) vs. 33 months (range, 9-267), respectively (P > .99). Of the 87 cases we reviewed from the literature, all but 1 (98.9%) had diagnoses based on symptoms. Multiple bone involvement and extraosseous dissemination were associated with poor prognosis. Type II endometrial cancer (i.e., serous or clear-cell histology) was associated with shorter life expectancy after diagnosis of bone metastasis compared to Type I tumors. CONCLUSIONS: The incidence of primary bone metastases of endometrial cancer is < 1%. Single bone metastases without extraosseous spread indicate less aggressive disease. Optimal treatment is unclear.
Matteucci E, Maroni P, Bendinelli P, et al. Epigenetic control of endothelin-1 axis affects invasiveness of breast carcinoma cells with bone tropism. Exp Cell Res. 2013; 319(12):1865-74 [PubMed] Related Publications
Here, we report a complex regulation of endothelin-1 (ET-1) axis driven by epigenetic reactions in 1833-bone metastatic cells, emphasizing the importance in skeletal metastasis from breast carcinoma. Inhibitors of histone deacetylases, trichostatin A (TSA), and of DNA methylases, 5'-Azacytidine (Aza), caused, respectively, reduction and increase in 1833 cell invasiveness, without affecting the basal migration of parental MDA-MB231 cells. Of note, in the two cell lines exposed to Aza the blockade of the ET-1 receptor ETAR with BQ-123 oppositely changed invasive properties. Even if in MDA-MB231 cells the ET-1 axis was scarcely influenced by epigenetic reactions, ETAR remarkably decreased after Aza. In contrast, in 1833 cells Aza exposure enhanced ET-1 coupled to ETAR wild type, being also ETAR truncated form increased, and invasiveness was stimulated. Under demethylation, the increase in ET-1 steady state protein level in 1833 clone seemed regulated at transcriptional level principally via Ets1 transcription factor. In fact, actinomycin D almost completely prevented ET-1 mRNA induction due to Aza. Only in 1833 cells, TSA exposure inactivated ET-1 axis, with reduction of the expression of ET-1 and ETAR mutated form, in agreement with Matrigel invasion decrease. This treatment favoured the ET-1 repressional control, taking place at the level of mRNA stability due to the 3'-untranslated region in the ET-1 gene, and also decreased transcription via NF-kB. Environmental conditions that alter the balance between epigenetic reactions might, therefore, affect metastasis migratory mode influencing ET-1 axis.
Guenette JP, Lopez MJ, Kim E, Dupuy DE Solitary painful osseous metastases: correlation of imaging features with pain palliation after radiofrequency ablation--a multicenter american college of radiology imaging network study. Radiology. 2013; 268(3):907-15 [PubMed] Article available free on PMC after 01/09/2014 Related Publications
PURPOSE: To identify the correlation of pre- and postablation imaging features with pain relief, pain intensity, and patient mood after radiofrequency (RF) ablation of solitary painful osseous metastases. MATERIALS AND METHods: This prospective, multicenter group trial was approved by each institutional review board. Participants were enrolled between November 1, 2001, and April 6, 2006. Written informed consent was obtained from all subjects, and patient confidentiality protocols were followed in compliance with HIPAA. Computed tomography (CT)-guided RF ablation and contrast material-enhanced 1-month follow-up CT and/or magnetic resonance imaging were performed in 49 subjects (24 men, 25 women; age range, 34-83 years) with a confirmed malignant solitary bone lesion of maximum dimension of 8 cm or smaller that was causing intractable pain. Pain intensity and patient mood were measured before and after RF ablation. Tumor imaging features were recorded. Unadjusted and adjusted linear mixed-effects models, with a random intercept for each subject, were used to model patient mood, pain relief, and pain intensity scores at three times after ablation as a function of each tumor characteristic. RESULTS: Decreased postablation tumor pain correlated with preablation tumor volume (P = .02) and pathologic fracture (P = .01), while pain relief correlated with pathologic fracture (P = .03) and percentage of bone-tumor interface (BTI) ablated (P = .02). Conversely, presence of an irregular rim after ablation (P = .02) and rim thickness (P = .01) correlated with increased pain. There was no evidence in this study that RF ablation of larger tumor percentage or larger volume leads to better pain relief or decreased pain (P > .05). CONCLUSION: Existing pathologic fracture and smaller tumor size appear to be predictive parameters of success when selecting patients for palliative RF ablation of painful solitary osseous metastases. Successful palliation also appears to be related to the percentage of BTI ablated.
Smidt-Hansen T, Folkmar TB, Fode K, et al. Combination of zoledronic Acid and targeted therapy is active but may induce osteonecrosis of the jaw in patients with metastatic renal cell carcinoma. J Oral Maxillofac Surg. 2013; 71(9):1532-40 [PubMed] Related Publications
PURPOSE: To investigate the efficacy and safety of zoledronic acid (ZA) combined with targeted therapy (TT). MATERIALS AND METHODS: A retrospective study was performed in patients with metastatic renal cell carcinoma treated with ZA and TT. RESULTS: Twenty-one patients received ZA and TT to prevent skeletal-related events and no pretherapy oral and maxillofacial (OM) examination (cohort A). Six patients (29%) developed osteonecrosis of the jaw (ONJ), which was observed only in patients receiving sunitinib and ZA. Sixteen patients received TT and ZA for hypercalcemia and no pretherapy OM examination (cohort B). In these patients, no ONJ was observed. Nine patients received ZA and TT and pretherapy OM examination (cohort C). One patient (11%) developed ONJ during sunitinib and ZA treatment. Mean skeletal morbidity rates were 0.8 for cohort A and 1.2 for cohort C. In the combined cohort (A plus C; n = 30), 47% developed skeletal-related events, 7% pathologic fracture, 7% medullary compression, and 37% progression of bone metastases. Patients who developed ONJ had a significantly improved median survival of 31.6 months compared with 14.5 months in patients without ONJ (P = .039). CONCLUSION: The combination of ZA and TT resulted in high, clinically meaningful activity. ONJ may be exacerbated by concomitant ZA and sunitinib. Regular OM examinations before and during treatment are recommended.