First Diagnosis Of Bone Metastases Research Articles

First prospective data on breast cancer patients from the multicentre italian bone metastasis database

Bone metastases (BM) are still the main cause of morbidity in cancer patients because of skeletal-related events (SREs) that reduce quality of life. They have also led to increased social and healthcare costs. At present, data available on BM are insufficient. This was a multicentre prospective observational study of patients with BM from breast cancer (BC) with at least 6 months’ follow-up. Information on patients at the first diagnosis of BM, including demographics and characteristics of the primary tumor and BM. Data were periodically updated by participating centres and reviewed by the coordinator centre. From October 2014 to July 2019, 618 patients with BM from solid tumors were enrolled and 220 were eligible for the present study. Median age was 62 years (range 26–86). Median follow-up was 34 months (range 6–149). At the time of enrolment, 109 (50%) had only BM (BOM) and 109 (50%) had concomitant visceral lesions and BM (BVM). Median time-to-first BM was 47 months (range 0–312) in BOM and 78.6 months in BVM patients. Disease-free interval differed on the basis of BC molecular subtype and stage. Ninety-eight BM patients had at least on SRE. Zoledronate was used in 69.1% of cases and denosumab in 28.3%. First-line treatment was hormone-based (50.7%), chemotherapy-based (38.7%) or chemotherapy- + hormone therapy-based (9.7%). Median progression-free and overall survival were 15.1 months (95% CI 12.6–18.4) and 66.8 months (95% CI 52.1–79.2), respectively. Our prospective study could substantially help to better understand the natural history of BM from BC.

Multicenter Italian bone metastasis database: First prospective data on breast cancer patients.

e13072 Background: Bone Metastases (BM) are still the main cause of morbidity and morbility in cancer patients because of their complications defined as skeletal-related events (SREs).SREs reduce pts quality of life and are associated with an increasing in social and health costs. At present, data concerning BM are mainly obtained retrospectively from monocentric experiences. Methods: We performed a multicentre prospective observational study of patients with BM from breast cancer (BC) with at least 6 month (m)'s follow-up who were registered in a prospective BM database (BMDB). Detailed information on patients at first diagnosis of BM was recorded in a custom-built software system, updated every 6 m by participating centres and reviewed by the coordinator centre.All pts have signed an informed consent. Results: Since October 2014,618 pts with BM from solid tumors were enrolled of whom 220 have BC as primitive site with a 6 m follow-up. Median age was 62 y (range 26-86). Median Follow up was 34 m (6-149). At enrolment 109 (50%) had only BM and 109 (50%) pts had concomitant visceral and BM. Median time to first BM was 47 m (range 0-312) in Bone only disease and 78.6 m in pts with visceral bone metastases. Disease Free interval (DFI) was different according to BC molecular subtypes and stage. The univariate hazard ratio (HR) for visceral or bone metastasis was higher in luminal B tumors (1.56, 95% confidence interval [CI]:1.1-2.3) (p = 0.002), basal-like (2.50, 95% CI:1.1-6.0) (p = 0.043), and HER2-enriched tumors (1.37, 95% CI:0.78-2.4) (p = 0.273). DFI for pts with stage I disease at diagnosis of primary BC was longer than that for stage III pts (median 67.2 m, 95%CI:53.1-96.1, vs. 58.1 m, 95%CI:41.9-73.4), with a HR of 1.84 (95% CI:1.1-3.0) (p = 0.015) for the stage III group, and 0.98 (95% C.I.:0.6-1.5) (p = 0.930) for the stage II group. During BM disease, 98 pts had at least 1 SREs . Zoledronate was used in 69.1% and Denosumab in 28.3% of cases. First line treatment was hormone-based (n = 105, 50.7%) chemo-based therapy (n = 80, 38.7%) and chemo+ormono based (n = 20, 9.7%). During follow up progression disease occurred in 167 pts. Median progression-free (mPFS) and overall survival calculated from metastatic disease diagnosis (mOS) were 15.1 m (95%CI 12.6-18.4) and 66.8 m (95%CI 52.1-79.2),respectively. Conclusions: This study presents prospective data about a cohort of BC pts enrolled at the first BM occurrence and followed over the time, extrapolated by the multicentric observational BMDB in order to better understed the clinical history of breast cancer and bone metastases.

Survival and prognostic factors in patients with stable and unstable spinal bone metastases from solid tumors: a retrospective analysis of 915 cases.

BackgroundAdequate prediction of survival plays an important role in treatment decisions for patients with spinal bone metastases (SBM). Several prognostic factors are already used in daily clinical practice, but factors related to stability of SBM are still unknown. Therefore, we designed this study to identify these prognostic factors.MethodsWe retrospectively assessed 915 patients from solid tumors with commonly metastased into the bone treated at our department between January 2000 and January 2012. Lung cancer (NSCLC), breast and renal cancer listed in Table 1 are the most common solid tumors with bone metastasis in this study. Prostate carcinoma was excluded due to osteoblastic SBM with no influence for stability. We calculated overall survival (OS) and bone survival (BS; time between first diagnosis of bone metastases until death) with the Kaplan-Meier method and assessed prognostic factors for BS with the log-rank test and a Cox regression model separately for patients with stable and unstable SBM.ResultsMedian follow-up was 9.3 months. OS after 6 months, 1, 2, and 5 years was 81, 62, 42, and 25 % in patients with stable SBM and 78, 57, 38, and 22 % in patients with unstable SBM (p = 0.851). BS was 57, 38, 22, and 5 % in the group of stable SBM after 6 months, 1, 2, and 5 years. For patients with unstable SBM BS after 6 months, 1, 2, and 5 years was 59, 39, 19, and 8 % (p = 0.755). In multivariate analysis we found male gender (HR = 1.27 [95 % CI 1.01–1.60], p = 0.04), Karnofsky performance status (KPS) <80 % (HR = 1.27 [95%CI 1.04–1.55], p = 0.02) and non-small cell lung cancer (NSCLC; HR = 2.77 [95%CI 1.99–3.86], p < 0.0001) to be independent prognostic factors for shortened survival in patients with stable SBM. Independent prognostic factors for unstable SBM were age per year (HR = 1.01 [95 % CI 1.0–1.02], p = 0.025), multiple SBM (HR = 1.35 [95 % CI 1.1–1.65], p = 0.003), and NSCLC (HR = 2.0 [95 % CI 1.43–2.80], p < 0.0001). Additionally, not wearing an orthopedic corset (HR = 0.77 [95 % CI 0.62–0.96], p = 0.02) was associated with prolonged BS in patients with unstable SBM and in both groups BS was significantly longer in patients without liver metastases (stable SBM: HR = 0.72 [95 % CI 0.56–0.92], p = 0.008; unstable SBM: HR = 0.71 [95 % CI 0.54–0.92], p = 0.01).ConclusionsSurvival was equal for patients with stable and unstable SBM. However, prognostic factors differed in both groups and stability should therefore be considered in treatment decision-making.

Prognostic factors for survival of women with unstable spinal bone metastases from breast cancer.

BackgroundBone metastases are an important clinical issue in women with breast cancer. Particularly, unstable spinal bone metastases (SBM) are a major cause of severe morbidity and reduced quality of life (QoL) due to frequent immobilization. Radiotherapy (RT) is the major treatment modality and is capable of promoting re-ossification and improving stability. Since local therapy response is excellent, survival of these patients with unstable SBM is of high clinical importance. We therefore conducted this analysis to assess survival and to determine prognostic factors for bone survival (BS) in women with breast cancer and unstable SBM.MethodsA total population of 92 women with unstable SBM from breast cancer who were treated with RT at our department between January 2000 and January 2012 was retrospectively investigated. We calculated overall survival (OS) and BS (time between first diagnosis of bone metastases until death) with the Kaplan-Meier method and assessed prognostic factors for BS with a Cox regression model.ResultsMean age at first diagnosis of breast cancer was 60.8 years ± SD 12.4 years. OS after 1, 2 and 5 years was 84.8, 66.3 and 50 %, respectively. BS after 1, 2 and 5 years was 62.0, 33.7 and 12 %, respectively. An age > 50 years (p < .001; HR 1.036 [CI 1.015–1.057]), the presence of a single bone metastasis (p = .002; HR 0.469 [CI 0.292–0.753]) and triple negative phenotype (p < .001; HR 1.068 [CI 0.933–1.125]) were identified as independent prognostic factors for BS.ConclusionsOur analysis demonstrated a short survival of women with breast cancer and unstable SBM. Age, presence of a solitary SBM and triple-negative phenotype correlated with survival. Our results may have an impact on therapeutic decisions in the future and offer a rationale for future prospective investigations.

379P - Risk Factors for Developing Skeletal-Related Events Associated with Metastatic Breast Cancer Patients Receiving Bone-Modifying Agents

ABSTRACT Aim: Bone-modifying agents (BMAs) reduce the incidence of skeletal-related events (SREs) and are recommended for breast cancer patients with bone metastasis. However, the risk factors for developing SREs, during BMA treatment, are not adequately studied. This study evaluated the time to first SRE and the time between first and multple SREs in order to identify the factors predicting SREs. Methods: The medical records of 534 women with breast cancer who developed bone metastasis, between 1999 and 2011, were reviewed. SREs were defined as a pathologic fracture, spinal cord compression, or the necessity of bone irradiation or surgery. The factors investigated included the type of primary cancer, performance status, menopause status, presence of extraskeletal metastasis, prior history of bone fractures and palliative radiation therapy, serum levels of lactate dehydrogenase and calcium corrected for albumin level at the time of the initial BMA dose, BMA type, and time between the first diagnosis of bone metastasis and the initiation of BMAs (0-6 months vs. above 6 months). These factors were analyzed using Cox proportional hazard analyses and Andersen-Gill approach. Results: Multivariate analyses indicated that significant baseline risk factors for the time to the first SRE included luminal B type disease (HR = 1.8, P = 0.006), presence of extraskeletal metastasis (HR = 1.7, P = 0.027), prior history of palliative radiation therapy (HR =1.7, P = 0.001), elevation of serum levels of calcium above normal (HR = 1.3, P = 0.002) on administyation of the initial BMA dose, or initiation of BMA treatment above 6 months (HR = 1.4, P = 0.044) after initial detection of bone metastasis. The significance of these factors was also observed in the analyses of multiple SREs. Conclusions: To reduce the risk of SREs, BMAs should be initiated within 6 months of the diagnosis of bone metastasis, and before commencing palliative radiation therapy in breast cancer patients. For patients with luminal B breast cancer and existing extraskeletal metastasis, BMAs should be continued whenever possible. Disclosure: All authors have declared no conflicts of interest.

Pure anti-tumor effect of zoledronic acid in naïve bone-only metastatic and locally advanced breast cancer: proof from the “biological window therapy”

The study investigated the anti-tumour effect of zoledronic acid (ZA) administered alone in a biological window therapy in naïve bone-only metastatic and locally advanced breast cancer (LABC) patients. 33 patients with LABC (Group 1) and 20 patients with a first diagnosis of bone metastasis only (Group 2) received 4 mg single dose of ZA, 14 days (biological window) before starting any treatment. In Group 1, Ki67, CD34, p53/bcl-2 and caspase 3 expression along with the adenosine triphosphate (ATP) levels and RNA disruption index were evaluated as markers of tumor growth in tumour specimens obtained before and after ZA administration (basal, day 14). In Group 2, the total enumeration of circulating tumour cells (CTCs), and of M30+ve CTCs along with the soluble marker of cell death (M30/M65) were carried-out as markers of tumor dissemination at baseline, at 48 h and day 14th. In Group 1, there was a significant reduction in Ki67, CD34, bcl-2 expression after 14 days ZA based-treatment (p = 0.0032; p = 0.0001, p < 0.00001 respectively). ZA showed a significant increase of RNA disruption (p < 0.0076). In Group 2, we observed a significant reduction of CTCs number after 48 h (p = 0.0012), followed by a significant rebound at 14 days (p = 0.012). The apoptotic CTCs/M30+ve and M65 levels significantly increased under treatment (p = 0.018 and p = 0.039 respectively) after drug administration when compared to the baseline. These results are the first prospective in vivo data showing the direct pure anti-tumour effect (either on the tumour cell or on CTCs) of ZA.

Elevated TNFR1 and Serotonin in Bone Metastasis Are Correlated with Poor Survival following Bone Metastasis Diagnosis for Both Carcinoma and Sarcoma Primary Tumors

There is an urgent need for therapies that will reduce the mortality of patients with bone metastasis. In this study, we profiled the protein signal pathway networks of the human bone metastasis microenvironment. The goal was to identify sets of interacting proteins that correlate with survival time following the first diagnosis of bone metastasis. Using Reverse Phase Protein Microarray technology, we measured the expression of 88 end points in the bone microenvironment of 159 bone metastasis tissue samples derived from patients with primary carcinomas and sarcomas. Metastases originating from different primary tumors showed similar levels of cell signaling across tissue types for the majority of proteins analyzed, suggesting that the bone microenvironment strongly influences the metastatic tumor signaling profiles. In a training set (72 samples), TNF receptor 1, alone (P = 0.0013) or combined with serotonin (P = 0.0004), TNFα (P = 0.0214), and RANK (P = 0.0226), was associated with poor survival, regardless of the primary tumor of origin. Results were confirmed by (i) analysis of an independent validation set (71 samples) and (ii) independent bioinformatic analysis using a support vector machine learning model. Spearman rho analysis revealed a highly significant number of interactions intersecting with ERα S118, serotonin, TNFα, RANKL, and matrix metalloproteinase in the bone metastasis signaling network, regardless of the primary tumor. The interaction network pattern was significantly different in the short versus long survivors. TNF receptor 1 and neuroendocrine-regulated protein signal pathways seem to play an important role in bone metastasis and may constitute a novel drug-targetable mechanism of seed-soil cross talk in bone metastasis.

Zoledronic acid effect on circulating RANK/RANK-l/OPG axis in cancer patients.

10615 Background: Bone metastasis disrupts bone integrity through loss of the balance between osteoclastic-mediated osteolysis and osteoblastic osteogenesis. The RANK/RANK-L/OPG axis governs osteoclastogenesis and bone resorption. We evaluated the trend of markers over time. Secondary aims were to study the predictive role of different circulating markers in the response to Zoledronic Acid (ZA) with respect to objective response and to skeletal-related events (SREs). Methods: The study prospectively evaluated levels of RANK, RANKL and OPG transcripts by Real-Time PCR and VEGF and NTX expression by ELISA in the peripheral blood of 49 consecutive patients with advanced breast, prostate or lung cancer (36, 7 and 6, respectively). Enrolled patients were at first diagnosis of bone metastases and had not previously undergone treatment with bisphosphonates. Patients received the standard schedule of ZA (4 mg infusion every 28 days) for about 12 months, undergoing blood tests and instrumental evaluation before the first infusion of ZA and every 4 months thereafter. Results: Median RANKL values after 12 infusions of ZA had decreased by 22% with respect to baseline whereas OPG, had increased by about 96%, with a 56% decrease in the RANKL/OPG ratio. NTX decreased over time (p&lt;0.0001). On the basis of ROC curve analysis, RANKL was the most accurate marker for bone response with an AUC of 0.74 (95% CI 0.54-0.93). No correlations were found between circulating markers and SREs. Conclusions: The present work is one of the few prospective studies carried out on the circulating markers that are potentially associated with bone metastases. Our findings would seem to indicate that ZA decreases osteoclast activity through RANK/RANKL/OPG pathway modulation and that RANKL may play a role in the prediction of objective response to ZA. Confirmation of results is needed in a larger case series.

Circulating levels of RANK/RANKL and OPG in patients with bone metastasis treated with zoledronic acid: A prospective study.

10611 Background: Bone metastases are the most frequent malignant disease of the bone and are responsible for high morbidity and reduced quality of life in cancer patients. Zoledronic acid (Zometa, Zol), routinely used in this subgroup of patients, inhibits bone resorption and has antitumor properties. It has also been reported to have an antiangiogenic effect. Methods: The study prospectively evaluated the levels of RANK, RANKL and OPG transcripts by real-time PCR in the peripheral blood of 49 consecutive patients with advanced breast, prostate or lung cancer (36, 7 and 6, respectively). Patients were eligible if they were at first diagnosis of bone metastases and if they had not previously undergone treatment with bisphosphonates. All patients received the standard Zol schedule of a 4-mg infusion every 28 days. Patients were monitored for about 12 months and blood samples were collected before the first infusion of Zol and every 4 months thereafter. Results: At least 3 blood samples were taken from all 49 patients (4 samples were taken from 29). Baseline RANK, RANKL and OPG median values were 78.3 (range 7.3-620.6), 319.1 (21.4-1884.4) and 1.52 (0.1-58.0), respectively. At 12 months RANKL median value had decreased by 22% with respect to baseline, whereas OPG median value had increased by about 96%. Consequently, the RANKL/OPG ratio decreased by 56% with respect to baseline. These differences, however, did not reach statistical significance, perhaps due to the small case series evaluated. Conversely, although RANK median values had increased by 36% at 8 months with respect to baseline, they had returned to near baseline values at 12 months. OPG, RANK and RANKL/OPG trends were significantly related. Conclusions: The present work is one of the few prospective studies to be carried out on circulating markers that are potentially correlated with bone metastases. It was observed that markers of the RANK/RANKL/OPG pathway in the peripheral blood of bone metastasis patients were probably modulated by Zol treatment. Zoledronic acid would appear to decrease osteoclast activity both directly and also via RANK/RANKL/OPG pathway modulation. Further investigation of the biological results is warranted.

Serum markers to monitor response to zoledronic acid in patients with bone metastases from breast cancer.

1105 Background: Breast cancer is the most frequent tumor in women and 80% of patients with advanced disease have bone metastases (BM), which are responsible for high morbidity and reducedquality of life. Zoledronic acid (Zol), routinely used to treat patients with BM, inhibits bone resorption andhas antitumor and antiangiogenic properties. Methods: The present study evaluated serum levels of vascular endothelial growth factor (VEGF) and cross-linked N-telopeptide of type I collagen (NTX) in 31 consecutive patients at first diagnosis of bone metastases. All received the monthly standard Zol treatment and were monitored for about 9 months with 3-4 blood samples collected from each patient during that time. Results: The baseline VEGF median value of 298 pg/ml (25-1264) increased to 345 pg/ml(62-977)at 3 months and, after falling to 307 pg/ml (112-1307) at 6 months, rose again, reaching 411 pg/ml (172-1004) at 9 months. However, these differences were not statistically significant. In contrast, the baseline ...

Potential usefulness of OPG, a member of the tumor necrosis factor receptor superfamily, for the early diagnosis of bone metastasis in breast cancer patients

e22000 Background: Breast cancer is the most frequent tumor in women. About 80% of patients with metastatic disease present bone involvement, in which the OPG/RANKL/RANK system would seem to play an important role. Our aim was to evaluate the potential usefulness of OPG bone marker for the early diagnosis of bone metastases. Methods: The study was carried out on 120 individuals: 30 healthy donors, with a median age of 40 years (21–76) and 90 breast cancer patients, with a median age of 57 years (30–86). Among patients, 49 were disease-free (median age 52 years) and 41 were at first diagnosis of bone metastases (median age 63 years). OPG transcript was determined in peripheral blood samples using quantitative PCR analysis. A receiver operating characteristic (ROC) curve was used to calculate the diagnostic accuracy of the marker. Results: OPG values were not correlated with age in any of the subgroups. The OPG median value was not statistically different in healthy donors (median=1.9; range 0.6–4.7) and disease-free patients (median=1.7; range 0.4–8.9), whereas it was threefold higher than that observed in relapsed patients (median=0.6; range 0.1–5.2; p&lt;0.001), regardless of the number of metastatic sites. The area under the curve (AUC) in disease-free patients was 0.82 for OPG, with 71% sensitivity and 88% specificity, using a cut off ≤ 0.8. In a parallel analysis of 37 patients (14 disease-free and 23 with bone metastases) for whom CEA and CA15.3 information was available, specificity for each marker was 100%, whereas sensitivity was only 61% and 59%, respectively. When these markers were considered in combination with OPG, an increase in sensitivity, albeit not statistically significant, was observed for CEA (83%) and CA15.3 (82%). Conclusions: Our preliminary data show a potential role of the OPG bone turnover marker for the early diagnosis of bone metastases. Results now need to be confirmed in a larger case series. No significant financial relationships to disclose.

Management of bone metastases in breast cancer

Patients with advanced breast cancer who develop bone metastases suffer an ongoing risk of skeletal complications that can have a significant impact on their quality of life (QoL). These complications include bone pain, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy (HCM), a potentially life-threatening condition. Treatment options include radiotherapy to palliate bone pain and/or prevent impending fracture, orthopedic surgery to prevent or repair fractures, analgesics, and bisphosphonates, which can significantly reduce the risk of skeletal complications and delay their onset. Of the known bisphosphonates, zoledronic acid is the most potent. Since its regulatory approval in the United States and Europe in 2001, zoledronic acid (4 mg by 15-minute infusion) has become widely used and has replaced pamidronate (90 mg by 2-hour infusion) as the standard of care for treating bone metastases from breast cancer and bone lesions from multiple myeloma. Zoledronic acid has also demonstrated significant long-term benefits in randomized trials in prostate cancer and other solid tumors, whereas other bisphosphonates have failed. In long-term, phase III clinical testing, zoledronic acid provided significant treatment benefits beyond those of pamidronate in patients with breast cancer and demonstrated a safety profile comparable with pamidronate. Therefore, zoledronic acid is now recommended from the first diagnosis of bone metastasis. Other intravenous bisphosphonates include clodronate and ibandronate. Both are approved in Europe, but their efficacy relative to pamidronate and zoledronic acid is not known.

Impact of skeletal complications on total medical care costs in prostate cancer patients with bone metastases

6057 Background: Prostate cancer patients with bone metastases often experience skeletal-related events (SREs) including pathological fracture, spinal cord compression, or pain requiring surgery, radiotherapy, or opioid analgesics. Previous studies have estimated the costs of SREs by tallying costs for services specifically attributable to these events. This approach may underestimate costs if SREs have effects on other services. Methods: We used a large US health insurance claims database (7/94 - 6/02) to quantify impact of SREs on total medical care costs in patients with bone metastases of prostate cancer. Subjects included in this analysis had ≥2 encounters with a diagnosis of primary prostate cancer and ≥2 encounters with a diagnosis of metastases to bone. Expected total medical care costs were compared for propensity-matched samples of patients with SREs versus patients without SREs. SREs were identified based on the occurrence on or after the date of first diagnosis of bone metastases, of (1) ≥1 encounter with a diagnosis of pathological fracture or spinal cord compression, or (2) ≥1 bone surgery or radiotherapy procedure, or (3) initiation of opioid analgesic therapy. Results: We identified 542 prostate cancer patients with bone metastases, including 282 (52%) with ≥1 SRE. After matching, there were 181 patients each in the SRE and no-SRE groups with mean follow-up of 13 and 10 months respectively. In the SRE group, expected costs of care directly attributable to SREs were $9,783 per patient. Expected total medical-care costs were $20,484 greater in SRE patients ($59,522 vs $39,038 in the no-SRE group) Conclusions: The costs of SREs in patients with prostate cancer and bone metastases are substantial and potentially greater than previously estimated. Treatments which prevent SREs, such as the intravenous bisphosphonate zoledronic acid, may reduce these costs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Aventis Oncology

Impact of skeletal complications on total medical care costs in prostate cancer patients with bone metastases

6057 Background: Prostate cancer patients with bone metastases often experience skeletal-related events (SREs) including pathological fracture, spinal cord compression, or pain requiring surgery, radiotherapy, or opioid analgesics. Previous studies have estimated the costs of SREs by tallying costs for services specifically attributable to these events. This approach may underestimate costs if SREs have effects on other services. Methods: We used a large US health insurance claims database (7/94 - 6/02) to quantify impact of SREs on total medical care costs in patients with bone metastases of prostate cancer. Subjects included in this analysis had ≥2 encounters with a diagnosis of primary prostate cancer and ≥2 encounters with a diagnosis of metastases to bone. Expected total medical care costs were compared for propensity-matched samples of patients with SREs versus patients without SREs. SREs were identified based on the occurrence on or after the date of first diagnosis of bone metastases, of (1) ≥1 encounter with a diagnosis of pathological fracture or spinal cord compression, or (2) ≥1 bone surgery or radiotherapy procedure, or (3) initiation of opioid analgesic therapy. Results: We identified 542 prostate cancer patients with bone metastases, including 282 (52%) with ≥1 SRE. After matching, there were 181 patients each in the SRE and no-SRE groups with mean follow-up of 13 and 10 months respectively. In the SRE group, expected costs of care directly attributable to SREs were $9,783 per patient. Expected total medical-care costs were $20,484 greater in SRE patients ($59,522 vs $39,038 in the no-SRE group) Conclusions: The costs of SREs in patients with prostate cancer and bone metastases are substantial and potentially greater than previously estimated. Treatments which prevent SREs, such as the intravenous bisphosphonate zoledronic acid, may reduce these costs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Aventis Oncology

Impact of skeletal complications on total medical care costs in lung cancer patients with bone metastases

6064 Background: Lung cancer patients with bone metastases often experience skeletal-related events (SREs) including pathological fracture, spinal cord compression, hypercalcemia, or pain requiring surgery, radiotherapy, or opioid analgesics . Previous studies have estimated the costs of SREs by tallying costs for services specifically attributable to these events. This approach may underestimate costs if SREs have effects on other services. Methods: We used a large US health insurance claims database (7/94 - 6/02) to quantify impact of SREs on total medical care costs in patients with bone metastases of lung cancer. Subjects included in this analysis had ≥2 encounters with a diagnosis of primary lung cancer and ≥2 encounters with a diagnosis of metastases to bone. Expected total medical care costs were compared for propensity-matched samples of patients with SREs versus patients without SREs. SREs were identified based on the occurrence on or after the date of first diagnosis of bone metastases, of (1) ≥1 encounter with a diagnosis of pathological fracture, spinal cord compression, or hypercalcemia, or (2) ≥1 bone surgery or radiotherapy procedure, or (3) initiation of opioid analgesic therapy. Results: We identified 534 lung cancer patients with bone metastases, including 295 (55%) with ≥1 SRE. After matching, there were 162 patients each in the SRE and no-SRE groups with mean follow-up of 6.3 and 4.5 months respectively. In the SRE group, expected costs of care directly attributable to SREs were $9,494 per patient. Expected total medical-care costs were $28,223 greater in SRE versus no-SRE patients ($59,926 vs $31,704 in the no-SRE group). Conclusions: The costs of SREs in patients with lung cancer and bone metastases are substantial and potentially greater than previously estimated. Treatments which prevent SREs, such as the intravenous bisphosphonate zoledronic acid, may reduce these costs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis Pharmaceutical Corp. Novartis Aventis Oncology Aventis Oncology

Impact of skeletal complications on total medical care costs in lung cancer patients with bone metastases

6064 Background: Lung cancer patients with bone metastases often experience skeletal-related events (SREs) including pathological fracture, spinal cord compression, hypercalcemia, or pain requiring surgery, radiotherapy, or opioid analgesics . Previous studies have estimated the costs of SREs by tallying costs for services specifically attributable to these events. This approach may underestimate costs if SREs have effects on other services. Methods: We used a large US health insurance claims database (7/94 - 6/02) to quantify impact of SREs on total medical care costs in patients with bone metastases of lung cancer. Subjects included in this analysis had ≥2 encounters with a diagnosis of primary lung cancer and ≥2 encounters with a diagnosis of metastases to bone. Expected total medical care costs were compared for propensity-matched samples of patients with SREs versus patients without SREs. SREs were identified based on the occurrence on or after the date of first diagnosis of bone metastases, of (1) ≥1 encounter with a diagnosis of pathological fracture, spinal cord compression, or hypercalcemia, or (2) ≥1 bone surgery or radiotherapy procedure, or (3) initiation of opioid analgesic therapy. Results: We identified 534 lung cancer patients with bone metastases, including 295 (55%) with ≥1 SRE. After matching, there were 162 patients each in the SRE and no-SRE groups with mean follow-up of 6.3 and 4.5 months respectively. In the SRE group, expected costs of care directly attributable to SREs were $9,494 per patient. Expected total medical-care costs were $28,223 greater in SRE versus no-SRE patients ($59,926 vs $31,704 in the no-SRE group). Conclusions: The costs of SREs in patients with lung cancer and bone metastases are substantial and potentially greater than previously estimated. Treatments which prevent SREs, such as the intravenous bisphosphonate zoledronic acid, may reduce these costs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis Pharmaceutical Corp. Novartis Aventis Oncology Aventis Oncology

BONE METASTASIS AFTER AN OPERATION FOR A BREAST CANCER FOR WHICH ADMINISTRATION OF LH-RH AGONIST WAS EFFECTIVE -REPORT OF A CASE

Breast cancer is a hormone dependent disease, and the usefulness of surgical ovariectomy had been established. After that, endocrine therapy has greatly advanced. In January, 1994, indication of goserelin acetate, a LH-RH agonist, for premenopausal women with breast cancer was approved, and is expected to be an alternative of surgical ovariectomy. In this paper our experience with an postoperative case of breast cancer with bone metastasis, in which the usefulness of LH-RH agonist regimen was able to confirm by a long-term observation, is presented with a review of the literature. A 53-year-old premenopausal women had a metastasis to the right intertrochanter of the femur one year and 11 months after an operation for a right breast cancer (T2aN0M0, Stage II). The bone not respond to chemotherapy. So administration of LH-RH agonist was started and CR was attained after one year. Two years later new metastatic lesion was detected in the first lumber vertebra and the patient was reted as PD. Radiation therapy at 40 Gy was added. There has been no sign of recurrence, as of 6 years and 10 months after the operation for the breast cancer or 4 years and 11 months after the first diagnosis of bone metastasis.