Diagnosis Of Bone Metastases Research Articles

Improved Survival After Multimodal Approach with 131I Treatment in Patients with Bone Metastases Secondary to Differentiated Thyroid Cancer.

Background: The objective of this study was to evaluate the overall survival (OS) of radioiodine (131I) treatments alone or combined with non-131I treatments in patients with bone metastases (BM) of differentiated thyroid cancer (DTC). Methods: This was a retrospective study of patients who were evaluated between 2001 and 2018 at MedStar Washington Hospital Center and who had DTC, BM, and at least one 131I treatment after the diagnosis of BM. The OS was analyzed by Kaplan-Meier survival curves and was compared by log-rank test between two groups: patients who received 131I treatments alone and those who received treatments combining 131I with non-131I treatments (CombTx). Non-131I treatments include surgery, radiofrequency ablation, cryotherapy, arterial embolization, external beam radiation, Cyberknife, systemic targeted therapy, and anti-resorptive medication. Results: A total of 77 patients met the above criteria and were followed up to 41 years. Thirty percent (23/77) of patients received 131I treatment alone, and 70% (54/77) received CombTx. For 131I treatment alone, the median survival was 3.9 years, and the 1-, 2-, 3-, 5-, and 10-year OS rates were 86%, 81%, 61%, 35%, and 23%, respectively. For CombTx, the median survival was 7.7 years, and the 1-, 2-, 3-, 5-, and 10-year OS rates were 96%, 92%, 86%, 69%, and 30%, respectively. Patients who had undergone initial 131I therapy within six months post thyroidectomy demonstrated a better median survival after BM diagnosis than those whose initial 131I therapy was six months or more after thyroidectomy (6.5 vs. 0.5 years; p < 0.001). Patients who received external beam radiation therapy demonstrated a better median survival than those who did not (7.8 vs. 4.4 years; p = 0.016). Patients who received denosumab demonstrated a better median survival than those who did not (7.7 vs. 5.2 years; p = 0.03). Patients who were <55 years of age at the initial diagnosis of DTC or at the initial diagnosis of BM had a better median OS than those diagnosed at ≥55 years of age (both p = 0.01). In the multivariate analysis, only age at initial diagnosis of DTC and initial 131I therapy within six months post thyroidectomy, and multiple 131I treatments were independent prognostic factors. Conclusions: In patients with DTC with BM, 131I treatment in combination with one or more non-131I direct and systemic treatments was associated with a significant increase in OS compared with those patients who were treated by 131I treatment alone.

Bone metastases treated with immune checkpoint inhibitors: A single center experience.

e14105 Background: We conducted a retrospective study to analyze the overall survival (OS) and progression free survival (PFS) among patients with bone metastases (BMs) from Non Small Cell Lung Carcinoma (NSCLC), Melanoma, Head and Neck Squamous Cell Carcinoma (HNSCC) and others (including genitourinary carcinoma) treated with immunotherapy (Nivolumab, Pembrolizumab, Ipilimumab or a combination). Methods: We retrospectively evaluated patients with BMs treated at our institute from 2012-2017 who received either immunotherapy alone or in combination with other therapies for BMs including: medical therapy (zoledronic acid or denosumab), radiation or surgery. Univariate analysis was utilized to analyze OS and PFS. Results: A total of 58 patients were identified, median age at diagnosis of BMs was 61 years (range 29 – 94). 39 patients were male (67.2%) and 47(81%) patients had good performance status (KPS 70-100) at the time of immunotherapy initiation. The median time to diagnosis of BMs was 11.4 months. 20 patients had a single BM, 16 had 2-4 BMs and 22 had ≥5 BMs. Axial-only BMs were seen in 27 patients, appendicular-only in 8 and both in 23 patients. 40 patients were symptomatic and 28 patients had skeletal events (pathological fractures, spinal cord compression or hypercalcemia). 51 patients had other metastatic sites at the time of initiation of immunotherapy. 25 patients received nivolumab, 20 patients received pembrolizumab and 4 patients received combination immunotherapy. 41 patients received additional treatments for BMs. The median OS from the start of immunotherapy was 5.15 months and median PFS was 3 months. On univariate analysis male sex (p = 0.03) and combination immunotherapy (p = 0.06) were associated with better OS. Patients who received additional treatments for BMs (p = 0.04) and combination immunotherapy (p = 0.02) had better PFS. Conclusions: Combination immunotherapy and use of additional treatment modalities for BMs is associated with better survival. Further analysis is required to validate these results. [Table: see text]

Characteristics and outcomes of patients with colorectal cancer and bone metastasis.

e15063 Background: Bone metastasis from colorectal cancer is a relatively rare phenomenon. The aim of this study is to identify the risk factors and survival patterns of bone metastasis after colorectal cancer diagnosis. Methods: A total of 23,846 colorectal cancer patients who were diagnosed between 1972 and 2017 at Mayo Clinic were included in the analysis. Freedom from bone metastasis since diagnosis at 5, 10, 15, 25 and 35-years were estimated using Kaplan-Meier method. Multivariable Cox regression models were used to assess the differences in overall survival rate for patients with different cancer sides and cancer locations. All tests were two-sided with alpha level set at 0.05. Results: A total of 798 (3.3%) patients had a diagnosis of bone metastasis after colorectal cancer diagnosis over a median follow up of 3.2 years. Thirty-five year freedom from bone metastasis was 83% (95%CI: 80%-86%) for all patients, and were 87.13%, 82.29% and 77.26% for left colon, right colon and rectal cancer patients. Male gender, recent surgical years, and higher cancer stage were associated with higher risk of developing bone metastasis after colorectal cancer diagnosis. Rectal cancer patients had higher hazard of developing bone metastases compared to left and right colon cancer patients. Conclusions: We were able to identify several patient and tumor-related factors associated with the development of bone metastasis in patients with colorectal cancer. The proportion and factors identified are similar to other studies. Future directions would be to analyze other molecular determinants within this subset of patients.[Table: see text]

Analysis of a neurosurgical directed acute spinal cord compression pathway at Michigan Medicine, a tertiary referral hospital.

e18285 Background: Spinal cord compression (SCC) is considered an oncologic emergency that is likely to severely impair patients’ quality of life if immediate action is not taken. Clinicians need a high suspicion to diagnose SCC, as the presenting symptoms are variable and nonspecific. To expedite the diagnosis and treatment of SCC, we instituted an emergent spine MRI imaging pathway that was led by the neurosurgeons and involved close collaboration with medical oncology and radiation oncology. Methods: The charts of all patients from July 2015 to June 2018 who underwent the “MR Spine Cord Compression Acute” imaging pathway at Michigan Medicine were reviewed. Electronic time stamps provided the time of the initial order, the time to scan completion, the time to scan reading, and the time to definitive intervention. The charts were reviewed for the initial neurosurgical physical exam, a presentation consistent with recent trauma, a previous diagnosis of malignancy, and a previous diagnosis of bone metastases. The type and timing of therapy, and survival following the imaging protocol were assessed. Results: 319 unique MRI exams were done over the three-year span, 155 of the patients had cancer, and 75 patients had SCC. The time from ordering of exam to performance is 2.91 hours (0 to 25.45), from performance to read 8.31 hours (0 to 75.25 hours). Time from MRI to intervention was 63.14 hours (0 to 432 hours) based on complex decision making around surgical vs. radiation vs. medical therapy. For the majority of patients who were diagnosed with SCC, the cause was secondary to tumor growth from contiguous spinal metastasis, and most had previously identified bone metastases. Degenerative disc extrusion was the most common cause of benign SCC. Conclusions: A neurosurgical directed standard imaging protocol is effective at rapidly diagnosing SCC. Malignant SCC is predominately treated surgically, but complex multi-disciplinary patient centered decision-making involving neurosurgery, radiation oncology, and medical oncology is frequently necessary to arrive at the appropriate treatment.

Detection of bone metastases through diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) compared with PET/CT 18F-NaF.

e23086 Background: To evaluate a diagnostic test which can allow the comparison between Diffusion-weighted imaging with background suppression (DWIBS) the novel diagnostic modality versus PET/CT 18F-NaF, the gold standard for the diagnosis of bone metastases (BM). Methods: University bioethics committee authorized the protocol. Patients with solid cancer and suspicion of BM (by clinical findings, imaging, and tumor biomarkers), who met inclusion criteria were included and provided their signed informed consent. The DWIBS in a MR 3.0 T was performed first and then the PET/CT 18F-NaF. Each study was interpreted blinded. Statistics to evaluate a diagnostic test were performed. Results: From April 2014 to April 2016, 91 patients (100%) were interviewed, 88 (93.4%) met the inclusion criteria. Nine patients (8%) were excluded: death 3, respiratory failure 2, refused participating 2, pacemaker 1, claustrophobia 1. Seventy-nine patients (86.8%) were included, of which 81.0% (64/79) were women. Primary cancer was: a) breast 73.4 b) prostate 15.2%; c) Non-Hodgkin lymphoma 2.5%; d) cervical 2.5%; e) thyroid 2.5%; f) lung 1.3%; g) colon 1.3%; and h) testicular 1.3%. Diagnostic performance of DWIBS compared to PET/CT 18F-NaF, sensitivity 88.1% (Confidence Interval [CI95%, 73.3-96.0), specificity of 48.7% (CI 95%, 31.9-65.6), PPV of 66.0% (CI 95%, 58.2-73.1), NPV of 78.3% (CI 95%, 59.7-89.7), PLR 1.7 (CI 95%, 1.2-2-4), NLR 0.2 (CI 95%, 0.1-0.6) and prevalence of 53.1% (CI 95%, 41.6-54.5). Results were stratified in quartiles (excellent, good, fair, and poor). Conclusions: DWIBS has excelent sensibility, fair specificity, good PPV, and excellent NPV. These data suggest DWIBS could be used as a proxy of PET/CT 18F-NaF.

Low paravertebral muscle mass in patients with bone metastases from lung cancer is associated with poor prognosis.

Low skeletal muscle mass has been associated with poor prognosis in patients with advanced lung cancer. However, little is known about the relationship between skeletal muscle mass and overall survival in patients with bone metastases from lung cancer. The objective of the present study was to evaluate the prognostic value of low trunk muscle mass in predicting overall survival in these patients. The data from 198 patients who were diagnosed with bone metastases from lung cancer from April 2009 to May 2017 were retrospectively reviewed. The areas of the psoas and paravertebral muscles were measured at the level of the third lumbar vertebra on computed tomography scans taken at the time nearest to the diagnosis of bone metastasis. Muscle area was evaluated for male and female cohorts separately using different cutoff points. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival. The overall survival of patients in the lowest quartile for psoas muscle area or paravertebral muscle area was significantly shorter than that of patients above the 25th percentile for muscle area (p < 0.001). Multivariate analyses showed that paravertebral muscle mass (hazard ratio, 1.73; 95% confidence interval, 1.17-2.56; p = 0.006), epidermal growth factor receptor-targeted therapy, and performance status were independent prognostic factors. Low paravertebral muscle mass was associated with shorter survival, independently of known prognostic factors.

Expert Consensus on the Diagnosis and Treatment of Bone Metastasis in Lung Cancer (2019 Version)

【中文题目：肺癌骨转移诊疗专家共识（2019版）】.

Early detection of bone metastases of hepatocellular carcinoma reduces bone fracture and paralysis.

With the improvement in survival of hepatocellular carcinoma patients, extrahepatic metastases have become a more frequent complication. Although pathological fractures or paralysis due to bone metastases deteriorate the quality of life of patients, no treatment guideline for bone metastases has been established. This study aimed to clarify the risk factors for these events and the clinical course of patients with bone metastases. Out of 783 hepatocellular carcinoma patients treated in our institution between 2009 and 2016, 76 patients with bone metastases were enrolled. They were divided into two groups by the trigger of bone metastases detection. One was those diagnosed by surveillance (surveillance group), and the other was those based on symptom presentation (non-surveillance group). We investigated the clinical features, risk factors for fractures or paralysis and prognostic factors for survival after bone metastases. Baseline characteristics and survival were not significantly different between two groups. Fractures or paralysis occurred in 10 patients (13.2%), and the frequency was significantly higher in the non-surveillance group (20.9%) than the surveillance group (3.0%) in univariate analysis (p = 0.036). The median survival after diagnosis of bone metastases was 11.7 months. Age over 75 years (p = 0.002), hepatitis C-virus etiology (p = 0.007) and Child-Pugh class B/C (p < 0.001) were significantly associated with a shorter survival in multivariate analysis, but fractures or paralysis did not affect the survival. Early diagnosis through surveillance for hepatocellular carcinoma bone metastases may prevent fractures or paralysis and lead to a better quality of life for these patients.

Clinical benefit of early treatment with bone-modifying agents for preventing skeletal-related events in patients with genitourinary cancer with bone metastasis: A multi-institutional retrospective study.

To evaluate the clinical benefit of bone-modifying agents and identify the risk factors of skeletal-related events in patients with genitourinary cancer with newly diagnosed bone metastasis. This was a multicenter retrospective study including a total of 650 patients with bone metastasis of the following cancer types: hormone-sensitive prostate cancer (n=443), castration-resistant prostate cancer (n=50), renal cell carcinoma (n=80) and urothelial carcinoma (n=77). Clinical factors at the time of diagnosis of bone metastasis were analyzed. Early treatment with bone-modifying agents was defined as follows: administration of bone-modifying agents before the development of skeletal-related events and within 6months from the diagnosis of bone metastasis. During the follow-up period (median 19.0months, interquartile range 6.0-43.8months), skeletal-related events were reported in 88 (20%) patients with hormone-sensitive prostate cancer, 17 (34%) patients with castration-resistant prostate cancer, 58 (73%) patients with renal cell carcinoma and 34 (44%) patients with urothelial carcinoma. Early treatment with bone-modifying agents significantly prolonged the time to the first skeletal-related event in castration-resistant prostate cancer, renal cell carcinoma and urothelial carcinoma, but not in hormone-sensitive prostate cancer. Bone pain and elevated alkaline phosphatase levels were independent predictive risk factors of the first skeletal-related event. The subgroup analysis showed that early treatment with bone-modifying agents was associated with prolonged time to the first skeletal-related events in patients with bone pain or elevated alkaline phosphatase levels. Early treatment with bone-modifying agents should be considered, especially for patients with bone pain and elevated alkaline phosphatase levels, to prevent skeletal-related events in patients with genitourinary cancer with bone metastasis.

Radium-223 (Ra-223) Therapy after Abiraterone: Analysis of Symptomatic Skeletal Events (SSEs) in an International Early Access Program (iEAP) in Patients with Metastatic castration-Resistant Prostate Cancer (mCRPC)

The Ra-223 Phase III study (ALSYMPCA) was conducted before abiraterone became available. The Ra-223 iEAP study included abiraterone-treated patients. Here we assessed SSEs, overall survival (OS) and bone health agent (BHA) use in Ra-223–treated patients who received abiraterone as a prior treatment. This open-label, single-arm trial enrolled patients with bone-predominant mCRPC (≥2 bone metastases). Patients who received prior anti-cancer therapies were included; use of BHAs (bisphosphonates and denosumab) was permitted before/during the study. Median follow-up was 7.5 months. Baseline characteristics, SSEs, (external beam radiation therapy, symptomatic pathological fractures, spinal cord compression or surgical intervention) and OS were analyzed descriptively for patients who completed prior abiraterone therapy and abiraterone-naïve patients. Of 708 mCRPC patients, 85% of prior-abiraterone and 36% of abiraterone-naïve patients had previously received docetaxel. During Ra-223 therapy, 14% and 17% of patients received concomitant bisphosphonates and 20% and 17% concomitant denosumab in the prior-abiraterone and abiraterone-naïve groups, respectively. Median time since diagnosis of bone metastasis and start of Ra-223 was 37 and 21 months in the prior-abiraterone and abiraterone-naïve groups, respectively. Median PSA at baseline in the prior-abiraterone group was 290 μg/l and 100 μg/l in the abiraterone-naïve group. Median OS was 15.9 months overall (11.2 months for prior-abiraterone and 17.1 months for abiraterone-naïve patients). More patients had SSEs in the prior-abiraterone group (26%) than the abiraterone-naïve group (14%); incidence of pathological bone fractures was similar in both groups (5% for both). Patients in the prior-abiraterone group had a longer time from diagnosis of bone metastasis to Ra-223 initiation. These patients seem to have more-advanced disease, as reflected by higher median baseline PSA and more patients with prior docetaxel therapy. Similar rates of pathological and non-pathological fractures were reported in Ra-223–treated patients regardless of prior use of abiraterone.

Optimizing antiresorptive treatment in patients with bone metastases: time to initiation, switching strategies, and treatment duration

PurposeThe aim of this study was to investigate the optimal use of antiresorptive therapy in patients with metastatic cancer in terms of time to treatment initiation, switching strategy in case of skeletal-related event (SRE) or skeletal disease progression, and treatment efficacy beyond 2 years.MethodsWe conducted a single-center retrospective cohort study including consecutive cancer patients with bone metastases that have received antiresorptive treatment between 2009 and 2015. The outcomes of interest were the time to first and subsequent symptomatic skeletal event (SSE), the skeletal morbidity rate, and the incidence of antiresorptive therapy-specific adverse events depending on the research question.ResultsIn total, 255 patients included in our study cohort. The time to treatment initiation (direct (n = 143 patients) vs. delayed (n = 87 patients) defined as > 3 months after diagnosis of bone metastases) was not found to influence the time to SSE in (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.65–1.34) with comparable toxicity. Switching strategy after first SRE or due to skeletal disease progression from bisphosphonates to denosumab was independently associated with longer time to SRE (HR 0.47, 95% CI 0.25–0.88, p value = 0.019) compared with continuation with the same bisphosphonate. Using the landmark approach at 24 months and including 121 patients that survived for more than 2 years, we found that treatment continuation beyond 2 years was associated with longer time to first SSE after 2 years (HR 0.41; 95% CI 0.19–0.93).ConclusionsOur hypothesis-generating results support a more individualized approach on antiresorptive treatment including the lack of detrimental effect when the treatment is delayed, the potential benefit of switching strategy after skeletal disease progression or SSE, and the benefit of continuing antiresorptive treatment beyond 2 years.

Pain prevalence and treatment in patients with metastatic bone disease.

The accomplishment of successful pain treatment requires evaluation, characterization and quantification. The present study characterized pain and survival in a cohort of patients with cancer with bone metastasis who were treated with intravenous bisphosphonates. A total of 84 patients self-completed the Brief Pain Inventory (BPI) and 36-Item Short Form Survey (SF-36), between November 2010 and March 2011 with a 5-year survival follow-up as a surrogate marker of cancer burden. The median age was 62 years old (34–85), 64% of patients were female and 58% of these females had breast cancer. In the population, self-reported pain was 91.6%, with 29 patients (34.5%) reporting severe pain (score 7–10). Among these patients, only 13 (44.8%) presented a similar report to that of their clinical files and 5 were undergoing treatment with strong opioids (17.2%). A total of 45 patients (46%) had not been prescribed analgesic drugs, of these patients, 32 were treated with a weak opioid, and 13 with a strong opioid. An association was observed between pain records and the prescribed analgesic (P=0.031). BPI maximum pain and overall survival data were analyzed, and a significant association was identified between male patients presenting severe pain and decreased survival (P=0.004). Male survival was associated with severe pain, which is consistent with other data. The results revealed a skeletal-related events (SRE)-free survival (time elapsed from diagnosis of the first bone metastasis to the first SRE) of 9 months (4.39–13.73, 95% CI) with a statistically significant difference between subgroups of time since diagnosis of bone metastasis (P=0.005). The added value of the present study is the suggestion that complete and accurate pain narratives are mandatory and may contribute to the optimization of analgesia, and may help to increase survival rates. Optimal pain management for patients with cancer remains an urgent requirement.

Diagnosis of Bone Metastasis in Patients Without a History of Cancer.

Diagnosing bone metastasis in patients without a history of cancer remains challenging. Diagnostic evaluation may be prolonged owing to difficulties in distinguishing between bone metastasis and common orthopedic diseases. We hypothesized that bone metastasis due to occult cancer would be more difficult to diagnose than bone metastasis in patients with a history of cancer. Few studies exist on the difficulty of diagnosing bone metastasis in patients without a history of cancer. Therefore, we reviewed the clinical course of patients with bone metastasis between January 2011 and December 2014. We reviewed patients with bone metastasis to determine the diagnostic rate at first visit, period from symptom-onset to first visit, period from first visit to diagnosis, and presence of severe skeletal-related events at diagnosis, and compared these between 27 patients without a history of cancer (Group A) and 54 patients with a history of cancer (Group B). The diagnostic rate at first visit was significantly lower (11.5% vs. 52.4%, p=0.00069), the period from first visit to diagnosis was significantly longer (median, 7 weeks vs. 3 weeks, p=0.018), and the presence of severe skeletal-related events at diagnosis was significantly higher (81.4% vs. 50.0%, p=0.05) in patients without a history of cancer compared with those with a history of cancer. The results of this study indicate that it is difficult to diagnose bone metastasis in patients without a history of cancer. This must be considered in the early diagnosis of bone metastasis to prevent severe skeletal-related events.

Bone-targeted agent treatment patterns and the impact of bone metastases on patients with advanced breast cancer in the United States

Objective: Bone metastases are common among patients with advanced breast cancer, putting patients at increased risk of skeletal-related events (SREs). This study described impact of bone metastases, utilization of bone-targeted agents (BTAs) and physicians’ decision processes for BTA use in advanced breast cancer.Methods: Data were collected using the Adelphi Breast Cancer Disease-Specific Programme in the United States. Physicians completed a detailed record for eligible patients (women ≥18 years, with stage IIIB–IV breast cancer).Results: Data available from 1276 patients with advanced breast cancer included 485 (38%) with bone metastases. Most (80%) reported pain at bone metastasis diagnosis; of those reporting pain, 55% reported moderate to severe pain. Among patients with bone metastasis, 69% received a BTA. Reasons for initiating BTAs were bone pain (32%) and an estimated high risk of SREs (25%). Reasons for not treating with BTAs were very recent diagnosis (37%), poor Karnofsky performance status (14%), perceived low risk of SREs (11%) and short life expectancy (11%). Zoledronic acid (48%) and denosumab (42%) were commonly used BTAs; the main reasons for initiating BTA treatment were long-term safety (28% and 32%, respectively) and efficacy in delaying SREs (15% and 31%, respectively). The analysis was not adjusted for age or other possible confounders.Conclusion: Bone pain is a common and sometimes severe symptom of bone metastases in advanced breast cancer and a common reason for initiating BTA treatment. Safety and efficacy were the main factors considered by physicians when selecting BTAs.

Role of Neutrophil to Lymphocyte Ratio or Platelet to Lymphocyte Ratio in Prediction of Bone Metastasis of Prostate Cancer.

Accumulating evidence has revealed that inflammation might play an important role in the genesis and development of cancer. High levels of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ration (PLR) are parameters of systemic inflammation which have been identified to be associated with poor prognosis in PCa. Bone is one of the most common sites of metastasis from prostate cancer; however, there are few studies concerning the correlation of NLR, PLR, and bone metastases in PCa. The aim of this study was to evaluate the performance of neutrophil to lymphocyte ratio (NLR) or platelet to lymphocyte (PLR) in diagnosis of bone metastasis of prostate cancer (PCa). Data of 74 PCa patients without metastases, 51 PCa patients with bone metastases, and 43 patients with benign prostatic hypertrophy (BPH) were retrospectively reviewed. The difference of patients' clinical and laboratory characteristics of the three groups was comparatively studied. ROC analysis was used to evaluate the benefit of adding NLR or PLR to prostate specific antigen (PSA) in prediction of bone metastases. Depending on this cutoff value, patients were divided into high-NLR or low-NLR group, high-PLR or low-PLR group. There were significant differences in NLR and PLR between groups with bone metastases and without bone metastases (p = 0.044; p = 0.030), while there was no significant difference between NLR and PLR of the patients with localized prostate cancer and BPH (p = 0.462; p = 0.102). NLR and PLR were correlated with PSA level in the patients with prostate cancer (p = 0.006, r = 0.247; p = 0.025, r = 0.200). The distribution of PSA showed significant differences between the high-NLR and low-NLR group, as well as between the high-PLR and low-PLR group. By applying the ROC curve method, the AUC values of PSA with NLR or PLR were 0.725 and 0.838 (0.763 - 0.913), respectively. Although PSA + PLR had the largest area, there was no statistical significance between PSA + PLR and PSA (p = 0.6992). NLR and PLR significantly increase in PCa patients with bone metastases and are valuable in the diagnosis of bone metastases in PCa patients.

The value of human epididymis protein 4 (HE4) as a serum tumor marker for accurate bone metastases finding by whole-body bone scintigraphy in lung cancer patients

The aim of our study was to correlate the serum concentration of human epididymis protein 4 (HE4) in lung cancer patients with the bone metastases detected by whole-body bone scintigraphy. The serum concentrations of HE4 were determined by electrochemiluminescence immunoassay method in 60 patients with lung cancer and in 10 persons without malignant disease (control group). All participants were examined by whole-body bone scintigraphy with hybrid gamma camera of type BrightView XCT. We found bone metastases in 25.0% of patients by whole-body bone scintigraphy and probable bone metastases in 18.3% of patients. We did not observe bone metastases in 56.7% of patients and in nobody from control group. We observed that 73.33% patients with bone metastases had more than 3 bone metastasis deposits. Patients had significantly increased concentration of HE4 (p < 0.0001). All three subgroups of patients (bone metastases, probable bone metastases, no evidence of bone metastases) had significantly increased concentration of HE4 compared to controls. The highest concentration of HE4 had 9 patients with small-cell lung cancer of whose 4 patients had bone metastases, 4 patients had probable bone metastases and one patient was with no evidence of bone metastases. We found that HE4 has a discriminatory ability to differentiate groups of patients and healthy controls, as well as within scaffold scintigraphy in patients with lung cancer (p = 0.0002). The serum concentration of human epididymis protein 4 was significantly increased in patients with lung cancer in comparison with persons of control group. A quarter of lung cancer patients had identified bone metastases by whole-body bone scintigraphy and approximately 20% of patients had probable bone metastases. The increasing serum concentrations of human epididymis protein 4 can have importance in the diagnosis of bone metastases in patients with lung cancer, in particular in small-cell lung cancer.

Diagnostic Value of Plain Radiography for Symptomatic Bone Metastasis at the First Visit.

To prevent and minimize skeletal-related diseases, early diagnosis of bone metastases is important. However, previous reports have shown that plain radiography has low sensitivity and fails to screen multiple asymptomatic lesions. Limited investigations have been reported on the value of plain radiography in the diagnosis of symptomatic bone metastases. Therefore, this study aimed to investigate the diagnostic utility of plain radiography for symptomatic bone metastasis. Two experienced orthopedic surgeons retrospectively evaluated the plain radiographs of 39 patients with symptoms during their first visit between 2011 and 2014 for bone metastases. Another 2 experienced orthopedic surgeons then reviewed the data using 2 reference standards, the clinical results and the retrospectively evaluated results, in a blinded manner. The data were then reviewed by 2 certified orthopedic surgeons and 7 orthopedic surgeons in training with differing years of experience in a blinded manner. The overall sensitivity of diagnosis of symptomatic bone metastasis using plain radiography at the clinic first visit was 71.4%. Upon blinded evaluation, the accuracy, sensitivity, and specificity were 55.8%, 54.3%, and 68.8% and 77.6%, 73.0%, and 85.7% for clinical results and results from 2 experienced orthopedic surgeons as a reference standard, retrospectively. There was a strong and significant correlation between the accuracy and observers' years of experience in orthopedic surgery among the orthopedic surgeons in training (R=0.942, p=0.0015). Plain radiography around the time of the first visit has a definitive role in the early diagnosis of symptomatic bone metastasis.

An Approach to Identify Delivery of Palliative Radiation Therapy Using Health Care Claims Data: A Proof-of-Concept Application of a Visual Analytics Tool.

There is limited information on the use of data visualization tools for health services research applications. We provide a proof-of-concept application that focuses on claims-based measures of palliative radiation therapy. We investigate whether a guided, data-driven investigation contributes information for subsequent statistical analysis and algorithm development. This retrospective cohort study used linked registry and claims data on men who were diagnosed with stage IV M0 or stage IV M1b prostate cancer between 2005 and 2009, with associated claims from 2005 through 2010, and receiving radiation therapy. Preprocessing of data was accomplished by using EventFlow software to investigate longitudinal patterns in claims for radiation therapy in the 13 months after cancer diagnosis. Guided by results from EventFlow, we developed descriptive statistics to investigate the length of radiation therapy, use of bone metastasis coding, and mortality between M1b and M0 patients. A total of 1,151 patients met the inclusion criteria. Taking advantage of the novel aggregation capability of EventFlow, we observed differences in the length of radiation therapy and the use of bone metastasis coding between men with (M1b) and without (M0) a diagnosis of bone metastasis. Seventy-nine percent of M1b patients received radiation for a duration ≤ 4 weeks, which suggested palliative radiation (to the bone). Seventy-six percent of M0 patients received radiation for ≥ 6 weeks, which suggested radiation to the prostate. Mortality was higher among those who received a shorter duration of radiation therapy compared with those who received a longer duration of therapy. Use of EventFlow, followed by statistical analysis of the linked registry and claims data, identified useful components of a claims-based measure of radiation to the bone.

Examination of burden of skeletal-related events in patients naive to denosumab and intravenous bisphosphonate therapy in bone metastases from solid tumors population

Objectives: Skeletal-related events (SREs), i.e. pathologic fractures, spinal cord compression, surgery and radiation to bone, are serious skeletal complications that occur frequently in patients with bone metastases (BMs) from solid tumors (STs). Clinical guidelines recommend treatment with denosumab and intravenous bisphosphonates (IVBPs) to prevent SREs. However, therapy may be delayed by physicians due to perceived low risk of SREs or for other clinical reasons. This study estimated SRE incidence rates in treatment-naive (i.e. no denosumab or IVBPs) patients with BMs from STs in the US.Methods: In this retrospective cohort study adult patients with diagnoses of BM and ST between 1 January 2008 and 31 March 2015 were identified from MarketScan Databases. All patients had ≥6 months of data before the first BM diagnosis date (index date) and were followed for ≥6 months from the index date until the earliest of inpatient death, initiation of denosumab/IVBP therapy or end of data. The Kaplan–Meier curve was used to estimate cumulative incidence of SREs. The incremental healthcare cost of SREs was estimated and compared to propensity score matched non-SRE patients.Results: A total of 47,052 patients met the study criteria. Using the Kaplan–Meier method the cumulative incidences of SREs among treatment-naïve patients were 39.9% (95% confidence internal [CI]: 39.4–40.4), 46.3% (95% CI: 45.8–46.8), 52.5% (95% CI: 51.9–53.2) and 59.4% (95% CI: 58.6–60.3) by month 6, 12, 24 and 48 post index date, respectively. The SRE group was associated with higher all-cause total healthcare cost per-patient-per-year compared to those without SREs ($168,277 vs. $101,020, p < .001).Conclusions: Almost half (46.3%) of the treatment-naïve population with BMs from STs experience SREs within 1 year of the first BM diagnosis. SREs were associated with an average $67,257 additional healthcare cost annually. Given the high SRE burden in these patients, early initiation of prophylactic therapy should be considered.

Challenges in the Diagnosis of bone Metastasis in Patients without a History of Malignancy at Their First Clinic Visit.

Many patients with bone metastases whose diagnoses came only after they had suffered aggravated conditions are still frequently encountered. However, there have been few studies regarding the early diagnosis of such metastases. We retrospectively reviewed the clinical courses of cases we experienced between 2004 and 2014 to clarify the practical situation of diagnosis of such bone metastases. We undertook a retrospective review of 56 of our patients with bone metastasis who had no history of malignancy at their first visit, who visited our departments between 2004 and 2014. The initial diagnoses at the first visit to any clinic, the period from the first visit to any clinic to diagnosis of bone metastasis, the process to make the diagnosis, the frequency of severe skeletal-related events at diagnosis, and the examination serving as the basis for diagnosis were evaluated. The diagnosis of bone metastasis was made at the first visit in only 6 of the 56 patients. Pathological fractures, paralysis and/or calcemia were seen in 62.5% of the patients at diagnosis of bone metastasis. The median period from the first visit to any clinic to diagnosis was 7.0 weeks. Typically, the diagnosis of bone metastasis was made only after aggravation. The most frequent examination to serve as the basis of diagnosis was magnetic resonance imaging. Diagnosis of bone metastasis is challenging in patients without a history of malignancy at their first visit. For early diagnosis, it is important to recognize this challenge and to keep it in mind together with ongoing observation.