Bone Metastases Research Papers - Academia.edu (original) (raw)

1 From the Department of Nuclear Medicine (UT, CG, HWDY, HAM) and Division of Breast Medical Oncology (SD, MC), University of Texas MD Anderson Cancer Center, Unit 1263, 1515 Holcombe Blvd, Houston, TX 77030. Received March 27, 2007;... more

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- Radiology, Metastatic Breast Cancer, Bone Metastases, Medical and Health Sciences

The evaluation of response of osseous metastases to systemic treatments is often low as a consequence of the different radiologic appearances that make objective assessment not only difficult but sometimes impossible. Radiographic evidence of recalcification, the UICC criterion of response, is often evident for 6 months and sometimes may be delayed even more. This accounts for lower response rates in bone with respect to other metastatic sites in clinical trials. A transient rise in bone formation indices may provide an early indication of bone healing and, along with measurement of symptomatic changes, could ameliorate the response evaluation. Among the biochemical markers of bone formation, total alkaline phosphatase (TALP) is widely employed, but it lacks specificity. Estimation of bone isoenzyme (E-BALP) by electrophoretic techniques is time consuming and semiquantitative. The immunoradiometric assay (I-BALP) seems to overcome these limitations. In this study, we compared the two methods of bone isoenzyme estimation with each other and with the levels of bone gla protein (BGP) and carboxyterminal propeptide of type I procollagen (PICP) in a group of 136 cancer patients with bone metastases stratified as having lytic or mixed and blastic lesions at X-ray, and in 62 cancer patients without apparent bone involvement. The same indices were also evaluated prospectively in a patient subset submitted to chemotherapy associated with pamidronate. The aims of the study were to evaluate whether I-BALP is superior to E-BALP and whether both methods of bone isoenzyme estimation are more advantageous than TALP, BGP, and PICP in the assessment of osteoblast activity either in baseline conditions or in response to treatment. In bone metastatic patients with lytic appearances, values above the cut-off limit were observed in 32.1%, 23.3%, 48.9%, 32.9%, and 14% for, TALP, E-BALP, I-BALP, PICP, and BGP, while the corresponding percentages in those with blastic/mixed appearances were 74.0%, 84.8%, 76.9%, 51.9%, and 43.8%, respectively. In the patients without bone involvement, values within the normal range were 90.2%, 98.2%, 89.6%, 71.7%, and 90.2%, respectively. Levels of TALP, E-BALP, and I-BALP were reciprocally correlated in the three groups examined. In bone metastatic patients, however, the degree of correlation of the enzymes with PICP and BGP was weak. Liver isoenzyme of alkaline phosphatase (LALP) was

- by P. Sperone and +1
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- Biomedical Engineering, Clinical Trial, X Rays, Liver

A stochastic entirely mechanistic model of metastatic progression of cancer is developed. Based on this model the joint conditional distribution of the ordered sizes of detectable metastases given their number, n, is computed. It is shown that this distribution coincides with the joint distribution of order statistics for a random sample of size n derived from some probability distribution, and a formula for the latter is obtained. This formula is specialized for the case of exponentially growing primary and secondary tumors and exponentially distributed metastasis promotion times, and identifiability of model parameters is ascertained. These results allow for estimation of the natural history of cancer. As an example, it is estimated for a breast cancer patient with 31 bone metastases of known sizes. The proposed model for the sizes of detectable metastases provided an excellent fit to these data.

- by Marco Zaider
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- Mathematics, Breast Cancer, Natural History, Medicine

A prospective double-blind randomized trial was conducted on 184 cancer patients with moderate to severe chronic pain to evaluate the analgesic efficacy and tolerability of diclofenac alone (50 mg q.i.d.) or in combination with a weak opioid (codeine 40 mg q.i.d.), or with an anti-depressant (imipramine, 10 or 25 mg t.i.d.). All demographic and clinical characteristics including cancer type, presence of bone metastases, baseline pain severity, neuropathic and nociceptive pain, and depressive state, were well balanced between the three treatment groups. The main analysis of the study was on the VAS scores at visit 2 (day 4). The mean VAS values for both associations imipramine plus diclofenac and codeine plus diclofenac were similar to the association placebo plus diclofenac. Patients on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn mainly for inadequate efficacy, while patients on codeine plus diclofenac discontinued equally for inadequate efficacy or adverse events. In conclusion, in a short-term evaluation the addition of a tricyclic anti-depressant or a weak opioid to diclofenac did not provide further analgesia with respect to diclofenac administration alone.

- by andres castro
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- Pain, Nonparametric Statistics, Chronic Pain, Cancer pain

Patients with bone metastases may experience pain, fatigue, and decreased mobility. Multiple medications for analgesia are often required, each with attendant side effects. Although palliative-intent radiotherapy (RT) is effective in decreasing pain, additional supportive care interventions may be overlooked. Our objective was to describe the feasibility of multidisciplinary assessment of patients with symptomatic bone metastases attending a dedicated outpatient palliative RT clinic. Consecutive patients referred for RT for painful bone metastases were screened for symptoms and needs relevant to their medications, nutritional intake, activities of daily living, and psychosocial and spiritual concerns from January 1 to December 31, 2007. Consultations by appropriate team members and resulting recommendations were collected prospectively. Patients who received RT were contacted by telephone 4 weeks later to assess symptom outcomes. A total of 106 clinic visits by 82 individual patients occurred. As determined by screening form responses, the clinical Pharmacist, Occupational Therapist, Registered Dietician and Social Worker were consulted to provide assessments and recommendations within the time constraints presented by 1-day palliative RT delivery. In addition to pain relief, significant improvements in tiredness, depression, anxiety, drowsiness and overall well-being were reported at 4 weeks. Systematic screening of this population revealed previously unmet needs, addressed in the form of custom verbal and written recommendations. Multidisciplinary assessment is associated with a high number of recommendations and decreased symptom distress. Our findings lend strong support to the routine assessment by multiple supportive care professionals for patients with advanced cancer being considered for palliative RT.

- by Sunita Ghosh
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- Social Work, Occupational Therapy, Pain, Depression

Aim: F-18 fluor choline-positron emission tomography/computed tomography (FCH-PET/CT) has emerged as a new diagnostic tool for the imaging of prostate cancer. In this study, we have evaluated the potential role of FCH-PET/CT for the assessment of bone metastases in patients with prostate cancer. Furthermore, we assessed the pattern of metabolic uptake by FCH in relation to morphologic changes on CT. Methods: Seventy men with biopsy-proven prostate cancer underwent FCH-PET/CT for preoperative staging or follow-up evaluation. Thirty-two patients were evaluated preoperatively, and 38 patients were referred for post operative evaluation of suspected recurrence or progression based on clinical algorithms. PET imaging consisted of a dynamic PET/CT acquisition of the pelvic region during 8 min (1-min frames) starting 1 min after i.v. injection of 4.07 MBq/kg/bw FCH which was followed immediately by a semi whole body acquisition. Results: Overall, 262 lesions showed increased uptake on FCH-PET. Two hundred ten lesions (210/262) were interpreted as bone metastases. The mean standardized uptake values (SUV) in all malignant lesions was 8.1±3.9. Forty-nine lesions (24%) had no detectable morphological changes on CT-probably due to bone marrow metastases. Fifty-six sclerotic lesions (having a Hounsfield unit (HU) level of more than 825) were interpreted as highly suspicious for metastatic bone disease on CT and/or other imaging modalities such as the bone scan but showed no FCH uptake. There was a significant correlation between tracer uptake as assessed by SUV and the density of sclerotic lesions by HU (r=−0.52, pG0.001). The sensitivity, specificity, and accuracy of FCH-PET/CT in detecting bone metastases from prostate cancer was 79%, 97%, and 84%, respectively. Conclusion: FCH-PET/CT showed promising results for the early detection of bone metastases in prostate cancer patients. We have found that a HU level of above 825 is associated with an absence of FCH uptake. Almost all of the FCH-negative sclerotic lesions were detected in patients who were under hormone therapy, which raises the possibility that these lesions might no longer be viable. However, clarification and the prognostic value of such lesions require further research.

- by Josef Hammer
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- Computed Tomography, Medicine, Molecular Imaging, PET imaging

types of cancer with systemic dissemination, especially breast cancer, prostate and lung cancer, with the incidence of approximately 70%, 70% and 35%, respectively. 3 Lesions occurring in breast, lung, prostate and kidney comprise 80% of all metastases to bone. 4 Bone metastases are associated with considerable skeletal morbidity, including severe bone pain, spinal cord or nerve root compression, pathological fractures and hypercalcaemia. Although the skeleton receives only 10% of the cardiac output, metastases in the skeleton are very common as compared to metastases to other tissues receiving a far greater amount of the cardiac output. The bone metastases are found almost invaria-

- by Primož Strojan
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- Bone Metastases

Skeletal metastases occur in many patients with different kinds of malignant tumors, especially in advance stage of breast cancer (in 47%-85% of patients), prostate cancer (33-85%), and lung cancer (32%-60%). The management of painful skeletal metastases is complicated and should be carried out by a multidisciplinary approach including conventional analgesics, antitumor therapy (chemo-and hormone therapy), osteoclast-inhibitory agents (bisphosphonates), corticosteroids, external-beam radiotherapy, surgery, and nuclear medicine therapy. The nuclear medicine therapy for palliation of pain from bone metastases is a systemic radionuclide therapy based on the use of radiopharmaceuticals. In several studies the efficacy of bone-seeking radiopharmaceuticals have been demonstrated in terms of pain reduction from diffuse skeletal metastases. In this review, we will summarize the current literature on bone-seeking radiopharmaceuticals for the treatment of painful bone metastases and the combination therapy with biphosphonates and chemotherapy.

- by 刚石
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- Pharmacology, Pharmacy, Cancer, Cancer Biology
- by Fadila Farsi and +3
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- Decision Making, Decision Trees, Multiple Myeloma, Decision Tree

Several interventional radiology procedures are available for the management of cancer pain. In this article, we will briefly review the different procedures and their value in the setting of cancer pain management under two main categories: indirect action (regional anesthesia from neurolysis) and direct action on the tumor. Percutaneous ablation of bone tumors: alcohol, laser, radiofrequency, microwaves, ultrasound, and cryoablation. Several indications have previously been validated, including thermal ablation of bone metastases with results superior to conventional therapies. Additional applications should be validated over the next few years.

- by G. Tsoumakidou
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- Algorithms, Pain, Ultrasound, Pain Management
- by Deborah Mayer
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- Nursing, Oncology Nursing, Bone Metastases

Image-guided ablation of bone tumors: revue of current techniques. J Radiol 2008;89:461-71 Multiple interventional radiology techniques are available for percutaneous ablation of bone tumors: alcohol, laser, radiofrequency, microwave, ultrasound, and cryogenic ablation. Several indications have already been validated, including radiofrequency ablation of osteoid osteoma and bone metastases, with results superior to conventional treatment. More indications should be added over the coming years. The purpose of this article is to review the principles of the different ablation techniques, summarize their respective indications and results and discuss their implementation and the eventual combination with cementoplasty techniques.

- by Afshin Gangi
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- Ultrasound, Interventional Radiology, Radiofrequency Ablation, Radiofrequency

A number of studies have demonstrated that bone scintigraphy has high sensitivity and efficacy in the early detection of bone metastases from several tumours, including breast cancer. Bone scintigraphy is the most definitive tool for diagnosing and monitoring metastatic spread of breast cancer. However, in the past decade there has been a wide debate on its impact on survival time, morbidity and quality of life. Worldwide economic restrictions and these studies have led to the adoption of an almost minimalist policy for breast cancer follow-up using evidence-based guidelines. The recommended breast cancer surveillance testing includes only a few procedures (history, physical and breast self-examination, patient education on symptoms, pelvic examination). The routine use of additional tests, such as blood cell count, tumour markers, liver ultrasonography, bone scan and chest X-rays, is not recommended. Accordingly, scintigraphy should be reserved for a limited number of patients. On ...

- by Lorenzo Maffioli
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- Computed Tomography, Clinical Trial, Breast Cancer, Quality of life
- by Philippe Clézardin
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- Breast Cancer, Prostate Cancer, Cancer treatment, Tumor microenvironment

In women who develop bone metastases from breast cancer (BC), interactions between tumor cells and osteoclasts within the bone lead to localized bone destruction and increase the risk of skeletal-related events (SREs). Bisphosphonates inhibit osteoclast-mediated bone resorption, and have been used extensively for treating post-menopausal osteoporosis and reducing the risk of SREs in patients with bone metastases. A number of clinical trials in women with early stage BC have demonstrated that adding bisphosphonates to adjuvant endocrine therapy can prevent bone loss and may prevent disease recurrence and improve disease-free survival. In women with bone metastases from BC, bisphosphonates have demonstrated efficacy for reducing skeletal morbidity and pain and improving quality of life. Recent economic analyses have demonstrated that bisphosphonate therapy is a cost-effective use of healthcare resources. This review summarizes the available data for bisphosphonate benefits in both the adjuvant and metastatic settings in the context of evolving clinical practice.

- by Louise Provencher
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- Cancer, Risk factors, Carcinoma, Breast carcinoma

Aims: To assess health-related quality of life (HRQOL) after palliative radiotherapy for painful bone metastases using a palliative questionnaire (European Organization for Research and Treatment of Cancer QLQ-C15-PAL). Materials and methods: Patients scheduled to receive palliative radiotherapy for painful bone metastases (n ¼ 178) completed the QLQ-C15-PAL questionnaire before treatment and at week 1, week 2, month 1 and month 2 after the first day of radiotherapy. A partial response (PR) or a complete response (CR) to radiotherapy was defined according to the International Consensus criteria. General linear regression was used to analyse changes in QOL in the entire cohort and within responders and non-responders to radiotherapy at all follow-up periods. Results: The overall radiotherapy response was 45% at week 1 (n ¼ 21) (41% PR, 4% CR), 62% at week 2 (n ¼ 28) (58% PR, 4% CR), 62% at month 1 (n ¼ 58) (60% PR, 2% CR) and 65% at month 2 (n ¼ 38) (60% PR, 5% CR). In general, a significant decrease in pain (P < 0.0001), insomnia (P < 0.0001) and constipation (P ¼ 0.004) was seen by month 1 after radiotherapy. In patients who responded to radiotherapy, overall QOL significantly improved by month 2 after radiotherapy (P ¼ 0.002). Radiotherapy responders also reported an improvement in emotional functioning together with a decrease in symptoms such as insomnia and constipation at month 1. No improvements were seen in any of the QLQ-C15-PAL scores for patients whose pain did not respond to radiotherapy. Conclusion: Radiotherapy responders showed not only an improvement in pain, but also in HRQOL as assessed by QLQ-C15-PAL. As early as 1 week after radiotherapy for bone metastases, a pain relief response was reported by patients.

- by Edward Chow
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- Pain, Palliative Care, Quality of life, Prospective studies
- by Luis Costa
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- Clinical Trial, Consensus, Bone Metastasis, Bone Disease

Goals of work Radiotherapy (RT) for palliation of pain due to bone metastases (BM) is effective but underutilized likely due to the traditional practice of separate clinic visits for consultation, treatment planning, and RT delivery. However, recent evidence proves one RT treatment is as effective as multiple for analgesia, enabling investigation of an alternative model of RT delivery, the rapid access palliative radiotherapy program (RAPRP). Materials and methods Prior to the start of the program, needs assessment was performed to determine the composition of the optimal team. Screening tools were implemented to streamline holistic, multidisciplinary assessment. An advertising strategy, treatment and research protocols, and mechanisms for patient feedback were established. After RAPRP implementation, patient outcomes such as symptom relief were tracked.

- by Sunita Ghosh
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- Radiation Oncology, Pain, Palliative Care, Quality of life

Background: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions... more

- by Nicolas Hart and +1
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- Bone Biology, Cancer, Breast Cancer, Exercise Science

The canine prostate gland shares many morphological and functional similarities with the human prostate and dogs are the only other large mammals that commonly develop spontaneous prostate cancer. However, the incidence of prostate cancer is much lower in dogs and the precise cell of origin is not known. Dogs with prostate cancer usually present with advanced disease that does not respond to androgen deprivation therapy. Similar to humans, affected dogs often develop osteoblastic bone metastases in the pelvis and/or lumbar spine with associated pain and neurological deficits. Other clinical signs include weight loss, lethargy, and abnormal urination and/or defecation.

- by N. Northrup
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- Surgery, Radiation, Spine, Treatment

The treatment of patients with cancer epitomizes the importance of using a collaborative team approach to optimize patient care. Physician team members most commonly are radiation oncologists, general surgeons, surgical oncologists, thoracic surgeons, neurosurgeons, and orthopedic surgeons. When patients are receiving chemotherapy, their medical oncologist frequently takes responsibility for coordinating care among the various team members and initiating consultations with necessary providers. When patients develop bone metastases or chemotherapy-induced bone loss (CTIBL), the orthopedic surgeon may be able to improve the patient's quality of life greatly. Procedures orthopedists perform most commonly include open reduction and internal fixations and arthroplasties (joint replacement surgery). Less invasive procedures currently being tested include stereotactic radiosurgery, radiofrequency ablation (RFA), and percutaneous cementoplasty. By understanding the options available to ...

- by David Aboulafia
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- Palliative Care, Arthroplasty, Bone Cements, Catheter ablation

Objetive To assess the safety and efficacy of FDG-PET in breast cancer in the diagnostic of primary tumours, lymph node staging, the detection of recurrent disease/metastases, and the assessment of chemotherapy treatment. Methods A systematic review was undertaken. A search was made for primary studies, other systematic reviews, and health technology assessment reports in different databases. Results A total of 73 reports were included. FDG-PET does not appear to be sufficiently accurate to be used in isolation for ruling out the presence of a primary tumour. In lymph gland staging, FDG-PET does not appear to be accurate enough to detect occult axillary metastases or micrometastases (sensitivity 20 and 50%, respectively); sentinel node biopsy is required for confirmation. In the detection of bone metastases, FDG-PET should be complemented with other tests such as bone gammagraphy or SPECT. The assessment of response to chemotherapy, there seems to be no uniform criterion for establishing a standardized uptake value (SUV) for FDG that would allow responders and non-responders to be distinguished. Conclusions FDG-PET is insufficiently sensitive to rule out small primary tumours. Due to the high number of false positives returned, it cannot replace axillary dissection in axillary lymph gland staging. A complete biochemical response identified by FDG-PET should not be relied upon to mean an absence of disease since the technique cannot detect residual microscopic elements.

186g Re]Re-HEDP is a radiopharmaceutical used for pain palliation in bone metastases from various primary tumors. The negatron emitter with <E β > = 357 keV 186g Re is suitable to irradiate cancer and inflammatory cells, but it needs labeling bis-phosphonates as vectors to reach target tissue. Paper radiochromatography was used to evaluate the radiochemical purity of [ 186g Re]Re-HEDP in radiopharmaceutical solution as well as in biological samples (serum and urine) from treated patients, in order to follow bone-targeting and excretion. Following the activity concentration in each sample vs. time it is effective to elaborate a bio-kinetic model of the radiopharmaceutical and to optimize administration protocols.

The Brief Pain Inventory-Short Form (BPI-SF) is widely used for assessing pain in clinical and research studies. The worst pain rating is often the primary outcome of interest; yet, no published data are available on its minimally important difference (MID). Breast cancer patients with bone metastases enrolled in a randomized, double-blind, phase III study comparing denosumab with zoledronic acid for preventing skeletal related events and completed the BPI-SF, FACT-B, and EQ-5D at baseline, week 5, and monthly through the end of the study. Anchor-and distribution-based MID estimates were computed. Data from 1,564 patients were available. Spearman correlation coefficients for anchors ranged from 0.33-0.65. Mean change scores for worst pain ratings corresponding to one-category improvement in each anchor were 0.26-1.04 for BPI-SF current pain, Ϫ1.40 to Ϫ2.42 for EQ-5D Index score, 1.71-1.98 for EQ-5D Pain item, Ϫ2.22 to Ϫ0.51 for FACT-B TOI, Ϫ1.61 to Ϫ0.16 for FACT-G Physical, and Ϫ1.31 to Ϫ0.12 for FACT-G total. Distribution-based results were 1 SEM ϭ 1.6, 0.5 effect size ϭ 1.4, and Guyatt's statistic ϭ 1.4. Combining anchor-and distribution-based results yielded a two-point MID estimate. An MID estimate of two points is useful for interpreting how much change in worst pain is considered clinically meaningful.

- by Susan Mathias
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- Breast Cancer, Medicine, Effect size, Monoclonal Antibodies

We report a patient with DTPA and DMSA uptake on unsuspected bone metastases. He had severe pain due to grade 3 hydronephrosis of his left kidney. When Tc-99m DTPA and DMSA renal scanning were performed for preoperative evaluation, abnormal radiopharmaceutical uptake on the iliac area was noted. Pancreatic adenocarcinoma metastases to bone were subsequently defined. This patient is a very demonstrative case in respect of having all DTPA, DMSA and HDP uptakes in bone metastases. The type of the tumor has to be added to the list of extrarenal uptake of DTPA and DMSA as a rare cause.

- by Tansel Balci
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- Kidney, Incidental Findings, Clinical Sciences, Radiopharmaceuticals

Magnetic resonance imaging (MRI) has become the preferred imaging modality for the evaluation of malignant disease in the bone marrow. Compared to bone marrow aspiration and biopsy, MRI is noninvasive and provides information by sampling a large volume of bone marrow. Due to disease-related alterations in the composition of bone marrow, MRI provides a very high sensitivity, but lacks specificity for most bone marrow disorders. However, MRI can be a very valuable diagnostic tool properly placed within the clinical context.

- by Martin Uffmann
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- Magnetic Resonance Imaging, Bone marrow, Differential Diagnosis, Clinical Sciences
- by Haladhar Dev Sarma
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- Pain, Palliative Care, Nuclear medicine, Gamma Spectrometry

is a new and attractive radiopharm aceutical for the treatment of bone pain due to metastases. As a product of a 188 W/ 188 Re generator it is convenient for clinical use. With a short physical half life of 16.9 hours and a maximal b -energy of 2.1 MeV, it is suitable for therapy. Methods: We investigated the influence of 188 Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function in 15 patients. All patients were interviewed using standardized questions before, and 1, 2, 3, 4, 8, and 12 weeks after therapy. Blood samples were drawn weekly for 12 weeks, and a blood count was performed. Patients underwent gamma camera imaging to determine the radionuclide accumulation 4, 20, and 28 hours after therapy. The patients were treated with 1600 to 3459 MBq of 188 Re-HEDP. Results: Patients showed an improvement of the Karnofsky performance index from 74 6 8% to 84 6 11% 12 weeks after therapy. This improvement was statistically significant (p 5 0.001). Eighty percent of the patients described pain relief and reduction of analgesics. Twenty percent of the patients could discontinue their analgesics. Mean platelet count decreased from (284 6 84)*10 3 /m l to (205 6 62)*10 3 /m l, and mean leukocyte count from (7.5 6 1.5)*10 3 /m l to (5.9 6 2.1)*10 3 /m l after therapy. The maximal differences between the values of platelets and leukocytes before and after therapy were not statistically significant (p 5 0.021 and p 5 0.094). Prostate specific antigen decreased from 95 6 83 ng/ml to 41 6 21 ng/ml, the difference was not statistically significant (p 5 0.443). The bone accumulation 4, 20, and 28 hours after therapy was 1.3 6 0.5%, 0.6 6 0.3%, and 0.45 6 0.2% of the injected dose of a single metastasis, and 57 6 17%, 15.5 6 2% and 11 6 3% in the whole body, respectively. The effective half-life of 188 Re-HEDP was 15.3 6 3.0 hours in the bone metastases, and 11.4 6 2.8 hours in the whole body. This corresponds to a residence time of 0.22 6 0.25 hours in the bone metastases, and of 10.54 6 2.59 hours in the whole body. Conclusion: In a small patient population, 188 Re-HEDP therapy for bone pain palliation was effective and was associated with minimal toxicity.

- by J. Kropp
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- Palliative Care, Rhenium, Aged, Bone Metastases
- by Michael Koutsilieris
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- Prostate Cancer, Dexamethasone, Bone Metastases

s u m m a r y Bone metastases have a major impact on morbidity and on mortality in cancer patients. Despite its clinical relevance, metastasis remains the most poorly elucidated aspect of carcinogenesis. The biological mechanisms leading to bone metastasis establishment have been referred as "vicious circle", a complex network between cancer cells and the bone microenvironment. This review is aimed to underline the new molecular targets in bone metastases management other than bisphosphonates. Different pathways or molecules such as RANK/RANKL/OPG, cathepsin K, endothelin-1, Wnt/DKK1, Src have recently emerged as potential targets and nowadays preclinical and clinical trials are underway. The results from those in the advanced clinical phases are encouraging and underlined the need to design large randomised clinical trials to validate these results in the next future.

- by Daniele Santini
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- Monoclonal Antibodies, Bone Metastases, Antineoplastic Agents, Endothelins

Disponible sur internet le 08 juin 2004

- by Anne Cotten
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- Computed Tomography, Bone Disease, Soft Tissue, Bone Metastases

Introduction Bone pain is a common symptom of metastatic disease in cancer, experienced with various intensities by about 30% of cancer patients, during the development of their disease, up to 60-90% in the latest phases. Discussion In addition to other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy, bone-seeking radiopharmaceuticals are also used for the palliation of pain from bone metastases. Substantial advantages of bone palliation radionuclide therapy include the ability to simultaneously treat multiple sites of disease with a more probable therapeutic effect in earlier phases of metastatic disease, the ease of administration, the repeatability and the potential integration with the other treatments. Conclusion The Therapy, Oncology and Dosimetry Committees have worked together to revise the EANM guidelines on the use of bone-seeking radiopharmaceuticals. The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients undergoing such treatment.

- by Glenn Flux
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- Pain, Palliative Care, Nuclear medicine, Europe

Knochenmetastasen gehen mit einer Reihe von Skelett ereignissen (SREs, skeletal related events) einher, wobei unter diesem Begriff sowohl Komplikationen (pathologische Frakturen, Rückenmarkkompression) als auch die Erforder nis einer therapeutischen Intervention (Radiotherapie, ope rative Eingriffe/chirurgische Intervention am Knochen) im Falle schmerzhafter u/o frakturgefährdeter Knochenläsionen subsumiert werden, welche die Lebensqualität und das Funk tionsniveau der Betroffenen negativ beeinflussen können. In Anbetracht verbesserter therapeutischer Möglich keiten für onkologische Erkrankungen und der damit asso ziierten Ver längerung des durchschnittlichen Gesamtüberlebens muss der Prävention und Verzögerung des Auftretens von SREs und der Vermeidung krankenhausabhängiger Therapien besondere Bedeutung beigemessen werden. In den vergan genen Jahren waren Bisphosphonate in Hinblick auf die Vermeidung von Skelettkomplikationen zusätzlich zu den verfügbaren tumorspezifischen medikamentösen Therapie verfahren (Chemotherapie, Hormontherapie) der Standard in der Behandlung von Patienten mit ossären Metastasen. Mittlerweile steht mit Denosumab, einem vollhumanen monoklonalen Antikörper, der über seine Bindung an den «receptor activator of nuclear factorkB»Liganden (RANKL) die osteoklastenmediierte Knochenresorption verhindert und dadurch spezifisch in den Knochenstoffwechsel einzu greifen vermag, eine zielgerichtete therapeutische Alter native zur Verfügung.

- by Guenther Steger
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- Breast Cancer, Quality of life, Bone Metabolism, Spinal Cord

Prostate cancer is the second leading cause of cancer-related death in men. A typical feature of this disease is its ability to metastasize to bone. It is mainly osteosclerotic, and is caused by a relative excess of osteoblast activity, leading to an abnormal bone formation. Bone metastases are the result of a complex series of steps that are not yet fully understood and depend on dynamic crosstalk between metastatic cancer cells, cellular components of the bone marrow microenvironment, and bone matrix (osteoblasts and osteoclasts). Prostate cancer cells from primary tissue undergo an epithelial-mesenchymal transition to disseminate and acquire a bone-like phenotype to metastasize in bone tissue. This review discusses the biological processes and the molecules involved in the progression of bone metastases. Here we focus on the routes of osteoblast differentiation and activation, the crosstalk between bone cells and tumor cells, and the molecules involved in these processes that are expressed by both osteoblasts and tumor cells. Furthermore, this review deals with the recently elucidated role of osteoclasts in prostate cancer bone metastases. Certainly, to better understand the underlying mechanisms of bone metastasis and so improve targeted bone therapies, further studies are warranted to shed light on the probable role of the premetastatic niche and the involvement of cancer stem cells.

- by Patrizia Serra
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- Cancer, Prostate Cancer, Signal Transduction, Osteoclasts

BACKGROUND: A study for pain relief therapy with 188Re-HEDP was done in patients with bone metastases secondary to breast and prostate cancer. MATERIALS AND METHODS: Patients received 1.3 or 2.2 GBq, in single or multiple doses. Platelets, white and red cells were evaluated during 11 weeks. Pharmacokinetic characterization was done from blood and urine samples for 5 patients along 24 hours. Urinary excretion was evaluated in other 16 patients during 6 hours. Bone uptake was estimated as remaining activity in whole body. Scintigraphic images were acquired at 2 and 24 hs post-administration. Absorbed dose in bone marrow was estimated with Mirdose3. Analgesics intake and pain score were daily recorded. Tumour markers (PSA, and Tn-structure) were monitored in 9 patients during 4 to 6 months. Single doses of low activity (1.3 GBq) were given to twelve patients. Nine patients received multiple doses. RESULTS: All except one patient had normal levels of platelets, white and red cells. Rema...

- by Eduardo Savio and +2
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- Prostate Cancer, Bone marrow, Medical Physiology, Haematological Parameters

Background Short-course radiotherapy is a common treatment for the palliation of painful osseous metastases. Pain flare can be problematic, but its incidence has previously not been well-documented. The objectives of this study were to determine (1) the incidence of pain flare after palliative radiation for painful osseous metastases, and (2) whether single-fraction radiotherapy increases the risk of pain flare. Materials and methods Patients accrued to a prospective randomized control trial comparing 8 Gy in one fraction to 20 Gy in five fractions (the Canadian Bone Metastasis Study) were approached to fill out a daily pain and analgesia diary for the 7 days post-radiotherapy. Patients assessed their average pain at the index site using the Present Pain Intensity (PPI) scale of the McGill–Melzack pain questionnaire and recorded their daily analgesic medications, which were translated into an analgesic score. Pain flare was defined as a two-point increase in the PPI with no decrease in analgesic score or a 50% increase in analgesic score with no decrease in PPI on at least two consecutive days. Results Forty-seven patients agreed to fill out the diary and 44 (94%) completed it. Fifteen of 44 (34.1%) patients experienced a pain flare that lasted a median of 3 days. Ten of 23 (43.5%) and 5/21 (23.8%) of patients who received 8 Gy and 20 Gy had a pain flare, respectively. Conclusions Pain flare is common after palliative radiotherapy for osseous metastases and patients receiving single fraction radiotherapy may be at higher risk. Further study is warranted to determine predictors and preventive interventions.

- by Peter Kirkbride
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- Pain, Palliative Care, Treatment Outcome, Bone Metastasis

To assess the effect of a multimodal group exercise intervention, as an adjunct to conventional care, on fatigue, physical capacity, general wellbeing, physical activity, and quality of life in patients with cancer who were undergoing adjuvant chemotherapy or treatment for advanced disease. Randomised controlled trial. Two university hospitals in Copenhagen, Denmark. 269 patients with cancer; 73 men, 196 women, mean age 47 years (range 20-65) representing 21 diagnoses. Main exclusion criteria were brain or bone metastases. 235 patients completed follow-up. Supervised exercise comprising high intensity cardiovascular and resistance training, relaxation and body awareness training, massage, nine hours weekly for six weeks in addition to conventional care, compared with conventional care. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Medical Outcomes Study Short Form (MOS SF-36), Leisure Time Physical Activity Questionnaire, m...

- by Morten Quist
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- Mental Health, Global Health, Quality of life, Physical Activity

A peripheral primitive neuroectodermal tumor (pPNET), most consistent with a human Ewing's sarcoma, is described in a 5-month-old male Australian Shepherd puppy. The first tumor site detected was in the left frontal bone of the skull with apparent subsequent rapid metastases to multiple sites in the axial and appendicular skeleton and bone marrow, kidneys, and perihyphophyseal meninges. Radiographically, all bone lesions were lytic and there was also a humeral bone fracture. Histologically, the tumor was diagnosed as a small round blue cell tumor. At this stage, the differential diagnosis included a lymphoma, rhabdomyosarcoma, and a PNET of the peripheral nervous system. However, the cells had positive expression of triple neurofilament antigens as detected immunocytochemically. The cells were negative for a broad panel of canine-specific leucocyte cell marker antigens for desmin, smooth muscle actin, synaptophysin, and CD99. Ultrastructurally, the cells contained occasional dense core neurosecretory granules and intermediate filaments with intercellular desmosomal-like junctions and abundant glycogen clusters. Based on the age of the dog, the clinical history, the distribution of gross lesions, histologic characteristics of a small round blue cell tumor, and immunocytochemical and ultrastructural evidence of neuroectodermal differentiation, a diagnosis of a pPNET similar to a human Ewing's sarcoma was made.

- by Andrew Bollen
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- Veterinary Pathology, Immunohistochemistry, Dogs, Fisheries Sciences
- by Markus German
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- Urology, Prostate Cancer, Cell line, Clinical Sciences

Purpose Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often overexpressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue 99m Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Methods Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using 99m Tc-EDDA/ HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, 99m Tc(V)-DMSA, 131 I-MIBG, 99m Tc-MDP, 111 In-DTPA-octreotide and 18 F-FDG-PET) and compared with 99m Tc-EDDA/ HYNIC-TOC.

- by Alberto Signore
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- Computed Tomography, Decision Making, Clinical Practice, Thyroid gland

The radiation absorbed dose in the rabbit bone delivered by 153 Sm±EDTMP (samarium ethylenediaminetetra methylene diphosphonic acid) and 89 SrCl 2 (strontium chloride) was measured by means of electron spin resonance (ESR). These radioisotopes are used in systemic radiotherapy for palliation of painful bone metastases. The knowledge of the dose is important in order to avoid side eects to the bone marrow. The ESR radiation dose signal was calibrated by the additive dose method using cobalt-60 gamma rays. For 153 Sm±EDTMP, the bone doses in three rabbits were (422), (521) and (522) cGy kg/MBq. For 89 SrCl 2 , a dose of (221) cGy kg/MBq was found in one rabbit. 7

- by Carlos F.O. Graeff
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- Palliative Care, Electron Spin Resonance, Strontium, Samarium

All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves, notochord remnants, etc.) can give rise to benign or malignant tumours. Bone metastases and intraosseous sites of haematological malignancies, lymphoma and multiple myeloma are the most frequent aetiologies, while primary bone tumours and meningeal or nerve tumours are less common. Some histological types have a predilection for the sacrum, especially chordoma and giant cell tumour. Clinical signs are usually minor, and sacral tumours are often discovered in the context of nerve root or pelvic organ compression. The roles of conventional radiology, CT and MRI are described and compared with the histological features of the main tumours. The impact of imaging on treatment decisions and follow-up is also reviewed.

- by Sylvia Neuenschwander
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- Biopsy, Multiple Myeloma, Three Dimensional Imaging, Bone marrow

Purpose The aim of this retrospective study was to determine whether patients with previous peptide receptor radionuclide therapy using high-activity 111 In-pentetreotide can be safely treated with 177 Lu-octreotate and whether addition... more

- by Michael S Michael
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- Survival Analysis, Adolescent, Prodrugs, Toxicity

Endovenous bisphosphonate therapy seems associated with osteonecrosis of the jaw. The aim of this study was to evaluate the additional diagnostic value of hybrid SPECT/CT in 99m Tc-methylene diphosphonate 3-phase bone scintigraphy of osteonecrosis of the jaw in bisphosphonate-treated patients. Methods: We studied 15 patients (12 women and 3 men) with extraoral tumors affected by lytic bone metastases and multiple myeloma. All patients were previously treated with intravenous bisphosphonates (zoledronic acid) for 1-3 y, were negative for dental disease at clinical examination, and had suspected osteonecrosis of the jaw. All 15 patients underwent panoramic x-ray orthopantomography, CT or MRI (or both), microbiologic examination, 3-phase bone scintigraphy, and SPECT/CT of the maxillary region. Results: Three-phase bonescintigraphy showed increased perfusion and an increased blood pool in 9 of 12 and 10 of 12 patients, respectively; at the metabolic phase, SPECT was positive in all patients and showed abnormal hyperactivity in the maxilla of 2 patients, in the mandible of 9 patients, and in both the mandible and the maxilla of 4 patients. Hybrid SPECT/CT was of particular value in 8 of 15 patients, allowing discrimination of the osteonecrotic core from nearby hyperactivity due to viable bone. Whole-body scintigraphy showed remote and multiple metastases in all patients. Orthopantomography showed nonspecific bone rarefaction in all patients but was not able to aid diagnosis of osteonecrosis of the jaw. CT and MRI showed anomalies in all symptomatic patients: CT was helpful in evaluating both cortical and trabecular bone aspects, and MRI was able to detect soft-tissue involvement but not cortical bone destruction. Conclusion: In appropriately selected oncology patients treated with bisphosphonates, an increased uptake of 99m Tc-methylene diphosphonate in maxillary bones may suggest probable osteonecrosis of the jaw. In such cases, SPECT/CT may be of value in increasing the diagnostic accuracy of bone scanning, providing a precise functional anatomic correlation for the definition of the extent of disease.

- by Fabio Cavalli
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- Magnetic Resonance Imaging, Nuclear medicine, Nuclear, X Rays

The aim of this prospective study was to determine the diagnostic value of Tc-99m MDP scintimammography (SMG) for the detection of breast cancer in patients with breast masses and to compare the results with Tc-99m MIBI scintimammography. Twenty patients, categorized as suspicious, positive or benign for breast cancer according to the mammographic findings were included in the study. Dual phase Tc-99m MIBI and Tc-99m MDP SMG were performed in the prone lateral position within 5 days of each other. Although early and late Tc-99m MIBI SMG showed equal (90.4%) sensitivity, the specificity of late Tc-99m MIBI (87.5%) was found superior to early (62.5%) imaging. The overall sensitivity and specificity of early Tc-99m MDP SMG were 71.4% and 62.5%, respectively. Although late Tc-99m MDP imaging showed 100% specificity, its sensitivity was only 23.8%. In the patients with palpable masses, both early Tc-99m MDP and Tc-99m MIBI showed equal sensitivity (100%), but the sensitivity of early Tc-99m MIBI (37.5%) was found slightly higher than Tc-99m MDP (25.0%) for nonpalpable breast lesions. The sensitivity of Tc-99m MIBI and Tc-99m MDP SMG in detecting metastatic axillary involvement was 66.6% and 50%, respectively. High sensitivity and specificity together with its low cost, easy availability and the possibility of detecting bone metastases seems to make Tc-99m MDP a contributive agent in the evaluation of breast lesions as an alternative to Tc-99m MIBI.

- by Hikmet BAYHAN
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- Breast Cancer, Clinical Sciences, Dual phase steels, Bone Metastases

We evaluated the hierarchical risk groups for the estimated survival of WHO grade III glioma patients using recursive partitioning analysis (RPA). To our knowledge, this is the first study to address the results of RPA specifically for... more

- by Charles Scott
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- Algorithms, Data Analysis, Palliative Care, Cancer

Prostate and mammary cancer bone metastases can be osteoblastic or osteolytic, but the mechanisms determining these features are unclear. Bone morphogenetic and Wnt proteins are osteoinductive molecules. Their activity is modulated by antagonists such as noggin and dickkopf-1. Differential expression analysis of bone morphogenetic and Wnt protein antagonists in human prostate and mammary cancer cell lines showed that osteolytic cell lines constitutively express in vitro noggin and dickkopf-1 and at least one of the osteolytic cytokines parathyroid hormone-related protein, colony-stimulating factor-1, and interleukin-8. In contrast, osteoinductive cell lines express neither noggin nor dickkopf-1 nor osteolytic cytokines in vitro. The noggin differential expression profile observed in vitro was confirmed in vivo in prostate cancer cell lines xenografted into bone and in clinical samples of bone metastasis. Forced noggin expression in an osteoinductive prostate cancer cell line abolished the osteoblast response induced in vivo by its intraosseous xenografts. Basal bone resorption and tumor growth kinetics were marginally affected. Lack of noggin and possibly dickkopf-1 expression by cancer cells may be a relevant mechanism contributing to the osteoblast response in bone metastases. Concomitant lack of osteolytic cytokines may be permissive of this effect. Noggin is a candidate drug for the adjuvant therapy of bone metastasis. (Am J Prostate and mammary cancer are among the leading cancers diagnosed and the second leading cause of cancer death in men and women, respectively. 1 Both cancers show a high propensity to metastasize to bone. Whereas prostate cancer (CaP) elicits predominantly an osteoblast response resulting in osteosclerotic lesions, mammary cancer (CaM) triggers preferentially an osteoclast reaction with bone resorption and consequent osteolytic lesions. 2 Osteolytic and osteosclerotic lesions are prone to pathological fractures. A better understanding of the mechanism(s) determining the osteoclast and osteoblast response to cancer metastases is essential for the identification of therapeutic strategies for prevention of pathological bone fractures in cancer patients.

- by Clemens Löwik
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- Cytokines, Bone Morphogenetic Proteins, Cell Differentiation, Mice