Metastatic Bone Disease In Patients Research Articles

Multi-field-of-view SPECT is superior to whole-body scanning for assessing metastatic bone disease in patients with prostate cancer.

The aim of this study was to compare the diagnostic performance of whole-body bone scintigraphy (WBS) and multi-field-of-view single photon emission tomography (multi-FOV SPECT) with 99mTc-oxidronate (99mTc-HDP) in patients with prostate cancer (PCa). In a prospective study, WBS and SPECT acquisitions were performed in 194 patients with histologically confirmed PCa and serum prostate-specific antigen (PSA) levels above 10 ng/mL. Scans obtained using the two modalities were interpreted separately. Clinical and biochemical follow-up, radiological studies and biopsies served as benchmarks for the assessments. The impact of PSA level on WBS and SPECT results was also evaluated. The patient-based sensitivity, specificity, accuracy, PPV and NPV values of SPECT examinations were higher than those of WBS, especially in patients with serum PSA levels <40 ng/mL. Multi-FOV SPECT proved to be more sensitive and specific than WBS in detecting bone metastases in PCa patients.

Burden of symptoms associated with development of metastatic bone disease in patients with breast cancer.

PurposeWomen with breast cancer frequently develop painful bone metastases. This retrospective study was designed to longitudinally characterize patterns of patient-reported symptoms among patients with breast cancer relative to the diagnosis of bone metastases.MethodsPatient records were identified from the Oncology Services Comprehensive Electronic Records (OSCER) database which includes outpatient oncology practices across the USA. Symptom burden was assessed by Patient Care Monitor (PCM) assessments, which are administered as part of routine care in a subset of these practices. Eligible patients were women diagnosed with breast cancer (ICD-9-CM 174.xx) who developed bone metastases (ICD-9-CM 198.5) and had ≥1 PCM assessment between January 2007 and December 2012. The pre-specified endpoint was the occurrence of moderate to severe symptom burden, defined as PCM score ≥4 (0–10 scale).ResultsOne thousand one hundred five women (median age, 61) met the eligibility criteria. Worsening of symptoms, particularly fatigue and pain, occurred in the months leading up to the diagnosis of bone metastases. After bone metastases diagnosis, the rate of increase in the proportion of patients experiencing moderate/severe symptoms slowed, but continued to climb during follow-up. Median time to moderate/severe symptoms was 0.9 month for fatigue, 1 month for pain, 2.9 months for trouble sleeping, and 7.7 months for numbness/tingling. Half of the patients received bone-targeted agents after diagnosis of bone metastases.ConclusionsSymptom burden, especially pain and fatigue, increased both before and after the diagnosis of bone metastases, highlighting the need for proactive monitoring and management of symptoms in breast cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s00520-016-3154-x) contains supplementary material, which is available to authorized users.

Metastatic bone disease in patients with neuroendocrine tumors

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract P3-10-01: Burden of symptoms associated with development of metastatic bone disease in patients with breast cancer

Abstract Background: Bone is the most common site of distant metastasis in advanced breast cancer patients (pts). Development of bone metastases (mets) is associated with substantial morbidity including skeletal complications, decreased quality of life, increased pain, and shortened lifespan. Pt burden of symptoms associated with bone mets has been assessed in tumor types other than breast or in metastatic disease not specific to bone. This study characterizes patterns of pt-reported symptoms over time among breast cancer pts with bone mets. Methods: The Oncology Services Comprehensive Electronic Records (OSCER) database was used to retrospectively identify women with breast cancer who developed bone mets during their care and had ≥1 ACORN Patient Care Monitor (PCM) assessment. The PCM summarizes symptoms on an 11-point scale (0 = not a problem to 10 = as bad as possible). Moderate/severe symptoms were defined by a PCM score ≥4. PCM items relevant to metastatic disease (fatigue, physical pain, trouble sleeping, numbness/tingling, anxious, loss of interest in others) were assessed. A generalized linear mixed model was used to evaluate symptom progression before and after bone mets diagnosis (dx). Kaplan-Meier methods were used to estimate time to development of and proportion of pts with moderate/severe symptoms after bone mets dx. Results: 1105 pts with breast cancer and bone mets were included. In general, the proportion of pts with moderate/severe symptom burden increased in the months (mos) before bone mets dx (Table 1). The odds (risk) of pts experiencing moderate/severe symptom burden increased in the mos leading up to bone mets dx, with a 9% increase per mo for both fatigue and physical pain, and a 19% increase per mo for numbness/tingling (P&amp;lt;0.001 for all). Non-significant changes were observed in the risk of pts experiencing trouble sleeping (3%), anxiousness (0%), or loss of interest in others (16%). After bone mets dx, the cumulative proportion of pts with moderate/severe symptom burden increased with time (Table 2). Median time to moderate/severe symptoms after bone mets dx was 1.4 mos for fatigue, 1.9 mos for physical pain, 3.9 mos for trouble sleeping, 9.3 mos for numbness/tingling, 20.6 mos for anxious, and was not reached for loss of interest in others. Table 1. Unadjusted proportion of pts with moderate/severe symptom burden before or at time of bone mets dxSymptom12 mos before dx6 mos before dxAt bone mets dxFatigue35%37%52%Physical pain29%34%47%Trouble sleeping22%25%28%Numbness/tingling16%18%19%Anxious14%16%23%Loss of interest in others4%6%6% Conclusions: These data from a large number of breast cancer pts treated at community oncology practices show that pts experience increasing symptom burden for a substantial period of time before bone mets dx. Most pts continue to experience burdensome symptoms after bone mets dx. These findings reinforce the need for multiple symptoms to be proactively monitored and managed in these pts. Table 2. KM estimate: cumulative proportion of pts with moderate/severe symptom burden after bone mets dxSymptom2 mos after dx12 mos after dxFatigue58%82%Physical pain51%74%Trouble sleeping39%64%Numbness/tingling26%53%Anxious27%46%Loss of interest in others9%22% Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-10-01.

Multi-field-of-view SPECT is superior to whole-body scanning for assessing metastatic bone disease in patients with prostate cancer

The aim of this study was to compare the diagnostic performance of whole-body bone scintigraphy (WBS) and multi-field-of-view single photon emission tomography (multi-FOV SPECT) with 99mTc-oxidronate (99mTc-HDP) in patients with prostate cancer (PCa). In a prospective study, WBS and SPECT acquisitions were performed in 194 patients with histologically confirmed PCa and serum prostate-specific antigen (PSA) levels above 10 ng/mL. Scans obtained using the two modalities were interpreted separately. Clinical and biochemical follow-up, radiological studies and biopsies served as benchmarks for the assessments. The impact of PSA level on WBS and SPECT results was also evaluated. The patient-based sensitivity, specificity, accuracy, PPV and NPV values of SPECT examinations were higher than those of WBS, especially in patients with serum PSA levels <40 ng/mL. Multi-FOV SPECT proved to be more sensitive and specific than WBS in detecting bone metastases in PCa patients.

Biochemical indices of bone turnover in stroke patients is comparable to that of hip fracture patients

Metastatic bone disease in patients with advanced cancer is frequently associated with skeletal complications. These can be debilitating, causing pain, impaired functioning and decreased quality of life, as well as reduced survival. This review considers how the management of metastatic bone pain might be optimised, to limit the considerable burden it can impose on affected patients. Cancer-related pain is notoriously under-reported and under-treated, despite the availability of many therapeutic options. Non-opioid and opioid analgesics can be used; the latter are typically administered with radiotherapy, which forms the current standard of care for patients with metastatic bone pain. Surgery is appropriate for certain complicated cases of metastatic bone disease, and other options such as radiopharmaceuticals may provide additional relief. Treatments collectively referred to as bone-targeted agents (BTAs; bisphosphonates and denosumab) can offer further pain reduction. Initiation of therapy with BTAs is recommended for all patients with metastatic bone disease because these agents delay not only the onset of skeletal-related events but also the onset of bone pain. With evidence also emerging for pain control properties of new anticancer agents, the potential to individualise care for these patients is increased further. Optimisation of care depends on physicians' thorough appreciation of the complementary benefits that might be achieved with the various agents, as well as their limitations. Appropriate anti-tumour treatment combined with early initiation of BTAs and adequate analgesia plays a key role in the holistic approach to cancer pain management and may minimise the debilitating effects of metastatic bone pain.

Metastatic Bone Disease in Patients with Solid Tumors–-Burden of Bone Disease and the Role of Zoledronic Acid

Bisphosphonates have become an integral component of the therapeutic repertoire for cancer patients at risk for skeletal-related events (SREs) such as pathologic fractures, bone pain requiring palliative radiotherapy, the need for orthopedic surgery, spinal cord compression, and hypercalcemia of malignancy because of bone metastases. Administered via monthly 15-minute infusion of up to 4 mg (depending on creatinine clearance rate), zoledronic acid (ZOL) has been approved for preventing SREs in patients with bone metastases from any solid tumor or bone lesions from multiple myeloma. Although there have been limited head-to-head comparison trials between bisphosphonates, ZOL displayed benefits beyond pamidronate in a large-scale comparative trial in patients with bone metastases from breast cancer. Monitoring of serum creatinine levels and oral health is important to ensure safety and comfort during treatment. In addition to the established benefits of bisphosphonates in the advanced cancer setting, there is a strong preclinical rationale and emerging clinical evidence that ZOL has antitumor activities and can delay metastasis in patients with early breast cancer. Studies are underway in patients with other tumor types, and the role of bisphosphonates is likely to evolve.

Ibandronate reduces skeletal morbidity in patients with breast cancer

Three phase III studies have assessed the efficacy of intravenous (IV) and oral ibandronate over 96 weeks for metastatic bone disease in patients with breast cancer. The primary endpoint for each trial was the skeletal morbidity period rate, defined as the number of 12-week periods with new bone complications, adjusted for the time spent on study. Both IV ibandronate 6 mg every 3 to 4 weeks and oral ibandronate 50 mg once daily significantly reduced the skeletal morbidity period rate compared with placebo ( P = .004 in each case). The studies were not powered to detect statistical significance on individual components of the skeletal morbidity period rate. Nevertheless, IV ibandronate significantly reduced vertebral fractures and the need for radiotherapy, while oral ibandronate led to significantly fewer bone events needing radiotherapy or surgery than placebo. Using a multivariate Poisson regression model, the mean reduction in the relative risk of new bone events compared with placebo was 40% with IV ibandronate 6 mg ( P = .0033), and 38% with oral ibandronate 50 mg ( P <.001). The clinical equivalence of IV and oral ibandronate was confirmed by a post-hoc Anderson-Gill analysis of time to multiple skeletal events. These results show that IV and oral ibandronate effectively reduce skeletal morbidity in breast cancer patients with bone metastases.

Effects of bisphosphonates and insulin-like growth factor-1 (IGF-1) on prostate cancer cells in vitro

4758 Background: The bisphosphonate (BP) zoledronic acid (Zol) reduces skeletal morbidity from metastatic bone disease in patients with prostate cancer, presumably through inhibition of osteolysis. Osteolysis undermines skeletal integrity and releases IGF-1, thus stimulating prostate cancer growth. In addition, BPs have been shown to inhibit cancer cell growth. Therefore, we investigated the effects of BPs on prostate cancer cell growth in vitro. Methods: The effects of clodronate (Clod), pamidronate (Pam), ibandronate (Iban), and Zol on human PC-3 cell growth and survival were investigated after 1–6 days in culture. Cells were grown in media containing 1 to 100 microM BPs in the absence or presence (for Clod and Zol only) of 100 ng/mL IGF-1. Cell survival and growth were assessed by MTT assay, DNA content, and crystal violet staining. Proportion of cells in G0/G1 phase was determined by fluorescent staining, and apoptotic cells were identified by annexin staining. Results: Cell survival was not affected by Clod, but decreased in a time- and dose-dependent manner with Pam, Iban, and Zol. The largest effect was observed after 6 days with 100 microM Zol. Clod and Pam had no significant effect on cell cycle distribution. In contrast, 100 microM Zol or Iban produced cell accumulation in G0/G1 after 1, 2, and 4 days. The percentage of apoptotic cells was increased 2-fold by both Pam and Zol, and 1.3-fold by Iban. Clod had no effect. In the presence of IGF-1, cell growth increased by 28% (standard error of the mean [SEM] = 5%) at day 2 and by 23% (SEM = 7%) at day 6 (P < .001). These mitogenic effects were blocked by 1 microM Zol. Cell proliferation in the presence of IGF-1 was blocked by 10 microM Zol, and 100 microM Zol resulted in 85% cell death at day 6. Mitogenesis by IGF-1 was blocked by 10 microM Clod, but cell growth was not inhibited even at 100 microM Clod. Conclusions: Therefore, BPs, especially Zol, have direct effects on prostate cancer cells, inhibiting growth through cytostatic, apoptotic, and antimitogenic activities. These activities could contribute to the beneficial effects of Zol in the treatment of prostate cancer-induced bone disease. No significant financial relationships to disclose.

Effects of bisphosphonates and insulin-like growth factor-1 (IGF-1) on prostate cancer cells in vitro

4758 Background: The bisphosphonate (BP) zoledronic acid (Zol) reduces skeletal morbidity from metastatic bone disease in patients with prostate cancer, presumably through inhibition of osteolysis. Osteolysis undermines skeletal integrity and releases IGF-1, thus stimulating prostate cancer growth. In addition, BPs have been shown to inhibit cancer cell growth. Therefore, we investigated the effects of BPs on prostate cancer cell growth in vitro. Methods: The effects of clodronate (Clod), pamidronate (Pam), ibandronate (Iban), and Zol on human PC-3 cell growth and survival were investigated after 1–6 days in culture. Cells were grown in media containing 1 to 100 microM BPs in the absence or presence (for Clod and Zol only) of 100 ng/mL IGF-1. Cell survival and growth were assessed by MTT assay, DNA content, and crystal violet staining. Proportion of cells in G0/G1 phase was determined by fluorescent staining, and apoptotic cells were identified by annexin staining. Results: Cell survival was not affected by Clod, but decreased in a time- and dose-dependent manner with Pam, Iban, and Zol. The largest effect was observed after 6 days with 100 microM Zol. Clod and Pam had no significant effect on cell cycle distribution. In contrast, 100 microM Zol or Iban produced cell accumulation in G0/G1 after 1, 2, and 4 days. The percentage of apoptotic cells was increased 2-fold by both Pam and Zol, and 1.3-fold by Iban. Clod had no effect. In the presence of IGF-1, cell growth increased by 28% (standard error of the mean [SEM] = 5%) at day 2 and by 23% (SEM = 7%) at day 6 (P < .001). These mitogenic effects were blocked by 1 microM Zol. Cell proliferation in the presence of IGF-1 was blocked by 10 microM Zol, and 100 microM Zol resulted in 85% cell death at day 6. Mitogenesis by IGF-1 was blocked by 10 microM Clod, but cell growth was not inhibited even at 100 microM Clod. Conclusions: Therefore, BPs, especially Zol, have direct effects on prostate cancer cells, inhibiting growth through cytostatic, apoptotic, and antimitogenic activities. These activities could contribute to the beneficial effects of Zol in the treatment of prostate cancer-induced bone disease. No significant financial relationships to disclose.

Zoledronic acid: a review of its use in patients with advanced cancer.

Zoledronic acid (Zometa), a parenteral bisphosphonate, is an inhibitor of osteoclast-mediated bone resorption and is used in the management of patients with cancer. Zoledronic acid 4 mg is administered as an intravenous infusion over 15 minutes. In the treatment of bone metastases, zoledronic acid is the first and only bisphosphonate to demonstrate efficacy in patients with a broad range of tumour types and in multiple myeloma. In well-designed trials, a single 4 mg dose of zoledronic acid showed good efficacy in the treatment of patients with hypercalcaemia of malignancy. Zoledronic acid 4 mg was superior to pamidronic acid 90 mg, administered as a 2-hour infusion, as assessed by normalised serum calcium concentrations 10 days after administration. In conjunction with antineoplastic therapy, zoledronic acid was an effective long-term (up to 25 months) treatment for skeletal-related events in patients with bone metastases associated with multiple myeloma or solid tumours. In patients with bone metastases secondary to breast cancer or bone lesions from myeloma, zoledronic acid was at least as effective as pamidronic acid, based on assessments of skeletal-related events 25 months after the start of treatment. In addition, compared with pamidronic acid, the overall risk of developing skeletal complications, including hypercalcaemia of malignancy, was significantly reduced in recipients of zoledronic acid. Compared with pamidronic acid, zoledronic acid reduced the risk of patients with breast cancer developing a skeletal-related event by an additional 20%. Zoledronic acid was significantly more effective than placebo on most efficacy measures in patients with bone metastases secondary to other solid tumours (e.g. lung, prostate) and showed sustained efficacy for up to 15 months. Preliminary data indicate that its efficacy in these patients is sustained for up to 24 months. Estimates of the cost effectiveness of zoledronic acid in the treatment of prostate cancer were consistent with those of other bisphosphonates, and cost-effectiveness ratios were within limits considered acceptable economic value. Zoledronic acid was generally well tolerated, with a tolerability profile similar to that of pamidronic acid and placebo. As with other bisphosphonates, deterioration of renal function has occasionally been reported in patients receiving zoledronic acid and monitoring of serum creatinine is recommended during treatment. The efficacy of zoledronic acid is therefore well established in patients with hypercalcaemia of malignancy and, for up to 25 months, in the treatment of complications arising from metastatic bone disease in patients with multiple myeloma or solid tumours. The clinical profile of zoledronic acid compares favourably with that of pamidronic acid in patients with cancer and zoledronic acid has a more convenient administration schedule with the potential for better compliance. Thus, zoledronic acid is an effective bisphosphonate and is positioned to play an important role in the management of advanced cancer patients with bone metastases.

Detection of micrometastatic prostate cancer cells in the bone marrow of patients with prostate cancer.

Thirty-five patients with prostate cancer were examined for micrometastases to the bone marrow using reverse transcription-polymerase chain reaction (RT-PCR) with primers specific for the prostate-specific antigen (PSA) gene. Of nine patients with bone metastases detectable by bone scan imaging, five patients had PSA mRNA expression in the bone marrow detectable by RT-PCR. Of 26 patients with negative bone scan findings, seven patients had PSA mRNA expression detectable in the bone marrow. RT-PCR could detect micrometastatic prostate cancer cells in the bone marrow that were not detectable by bone scan imaging. Of 16 patients with a serum PSA concentration of 25 ng ml(-1) or greater, only nine (56.3%) had bone metastases detected by bone scans. Of the remaining seven patients, five had micrometastases to the bone marrow detected by RT-PCR. Overall, 14 of 16 patients (87.5%) with a serum PSA concentration of 25 ng ml(-1) or greater had metastatic bone diseases including bone marrow micrometastases. Of 19 patients with a serum PSA concentration of less than 25 ng ml(-1), two (10.5%) had only micrometastatic disease detected by RT-PCR. A significant correlation was observed between the incidence of bone involvement and the serum PSA concentration. This study suggests that RT-PCR will potentially develop into a relevant tool to assess bone involvement including bone marrow micrometastases and establish a precise correlation between serum PSA concentration and metastatic bone disease in patients with prostate cancer.

The cellular basis of metastatic bone disease in patients with lung cancer.

Histologic patterns of tumor-bone interaction were systematically evaluated in 80 cases of metastatic lung cancer involving bone. Patterns of tumor-bone interaction varied with the histologic type of lung cancer, reflecting the biochemical and biologic differences among the different types of lung cancer. Evidence presented here suggests that destruction of bone by metastatic lung cancer is mediated neither by direct contact of tumor cells with bone matrix nor by release of diffusible substances that lyse bone matrix. Among indirect mechanisms, the most prevalent and important was the activation of bone-lining cells by metastatic tumor. Epidermoid carcinomas in particular were associated with histologic patterns of classical bone remodelling, including osteoblastic, osteoclastic, and osteocytic activity. Adenocarcinomas showed a particularly high association with microfractures and manifested a stromal pattern consistent with release of prostaglandins. Ischemic necrosis of bone due to compression of vessels by expanding tumor mass is also a common and important mechanism. Correlation of histologic patterns with reported data on the frequency of metastases and syndromes of ectopic hormone production provides insight into the mechanism(s) of paraneoplastic hypercalcemia in patients with lung cancer.

Monarthric Arthritis Caused by Metastatic Breast Carcinoma

ALTHOUGH breast carcinoma commonly metastasizes to bone, involvement of the knee is unusual. In his review of metastatic bone disease in patients with breast cancer, Galasko¹mentioned no such instance. We report a patient with widespread mammary carcinoma in whom metastatic cancer of the knee was diagnosed by cytologic examination of the synovial fluid. <h3>Report of a Case</h3> In 1962, a woman, then 44 years old, underwent right radical mastectomy with postoperative irradiation for infiltrating ductal carcinoma with metastases to local lymph nodes. She was free of symptoms for five years. In 1967, chest pain, cough, and hemoptysis led to roentgenographic observation of a solitary coin lesion in the right lower lobe of the lung. The lesion regressed in response to estrogen therapy. In 1971, she felt persistent pain in the left knee. Roentgenographic bone survey and radioisotope bone scan showed no abnormality, and the knee showed only minimal degenerative