Evaluation Of Bone Metastases Research Articles

18F-fluorodeoxyglucose positron emission tomography-computed tomography in the localization of the lesions in the osteogenic region of breast cancer bone metastases after therapy.

Accurate efficacy evaluation of bone metastases (BMs) from breast cancer (BC) is an intractable issue in clinical practice, for which solutions are urgently needed. This study aimed to investigate the utility of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in the response evaluation of bone metastasis of BC. In total, 22 patients diagnosed with BC and BM were enrolled. These patients underwent repeated 18F-FDG PET/CT evaluations. The patients and each BM site were divided into two groups based on their response to treatment: progressive disease (PD) and nonprogressive disease (non-PD). We analyzed and compared the changes in PET and CT images, as well as the serum concentration of carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153), alkaline phosphatase (ALP), and calcium (Ca) over the same time frame. The immunohistochemistry (IHC) of primary lesions between groups and between the primary focus and BM with high 18F-FDG uptake were compared and analyzed. Maximum standard uptake value (SUVmax) after therapy [area under the curve (AUC): 0.932] and Δ-value of SUVmax (AUC: 0.811) on 18F-FDG PET imaging proved significantly valuable for the efficacy of therapy outcomes related to BM lesions (P<0.05). In terms of overall evaluation of BM, age and human epidermal growth factor receptor 2 (HER2) expression were significantly lower in the PD group than in the non-PD group (P<0.05). There were marked differences in CEA after therapy, the changes of CEA, and CA153 (∆-value) between the groups (P<0.05). The SUVmax and Ca concentration after therapy and ∆-value of SUVmax, along with the levels of CA153, CEA, and ALP, were valuable indicators for evaluating the efficacy of individual BMs (P<0.05). IHC of BM in the PD group showed differences compared to primary lesions, with antigen Ki-67 being downregulated in metastatic lesions and HER2 being downregulated in a portion of BMs (2 of 6). Meanwhile, the expression of estrogen receptor (ER) and progesterone receptor (PR) remained relatively unchanged. 18F-FDG PET/CT confers precise assessment of the posttreatment efficacy pertaining to BM in BC. This modality facilitates the identification of poor effect lesions following extant therapies and localization for pathological assessment and may substantially contribute to evaluating therapeutic efficacy, refining treatment strategies, and predicting the disease trajectory of patients with BC and BM.

Diffused Pulmonary Uptake of Tc-99m Methylene Diphosphonate Bone Scan in Patient with Prostate Cancer without Blood Test and Correlative/Cross-Sectional Imaging Abnormalities: A Case Report

Introduction: Bone scan using Tc-99m methylene diphosphonate (MDP) is a commonly used procedure for evaluating bone metastasis in cancer patients. Extra-osseous pulmonary uptake in bone scans is mostly an incidental finding and occurs in a multitude of disorders. Clinicians should be alert to any findings on clinical or complementary diagnostic tools. We presented a case of prostate cancer male patients who demonstrated diffuse pulmonary uptake on Tc-99m MDP bone scan without any blood test and correlative/cross-sectional imaging abnormality Case Presentation: An 80-year-old male with adenocarcinoma of the prostate with a Gleason score of 6 (3+3). The PSA level was 0.009. The patient had a history of recurrent atrial fibrillation (AF), postural dizziness, HTN, Gout, and chronic renal failure, but all of these comorbidities were under control. The patient underwent a bone scan to annually check for the presence of bone metastases. Three hours after administering 740 MBq Tc-99m MDP intravenously. The reports didn’t show any increased uptake that would indicate metastases in the bones. Instead, diffuse bilateral pulmonary uptake and a mild increase in cardiac uptake were present. On the same day, a computed tomography (CT) scan of the thorax revealed 3 micro-nodules in the right upper lung that were described as benign lesions, and a chest X-ray confirmed normal results. The patient’s laboratory results were within normal range, and there were no clinical lung symptoms or complaints. Considering the patient history of persistent AF, chronic renal failure, and a complaint of postural dizziness, the bone scan finding may indicate involvement of amyloidosis. The relationship between amyloidosis and cancer was also widely noted. Conclusions: Tc-99m MDP may play a role in evaluating amyloidosis involvement in an uncommon place such as the lungs. Future research should focus on analyzing diagnostic options in the patient’s condition in this situation. Keywords: cancer, diffused pulmonary uptake, amyloidosis, bone scan

Pretreatment level of serum sialic acid predicts both qualitative and quantitative bone metastases of prostate cancer.

Recently, serum sialic acid (SA) has emerged as a distinct prognostic marker for prostate cancer (PCa) and bone metastases, warranting differential treatment and prognosis for low-volume (LVD) and high-volume disease (HVD). In clinical settings, evaluating bone metastases can prove advantageous. We aimed to establish the correlation between SA and both bone metastasis and HVD in newly diagnosed PCa patients. We conducted a retrospective analysis of 1202 patients who received a new diagnosis of PCa between November 2014 and February 2021. We compared pretreatment SA levels across multiple groups and investigated the associations between SA levels and the clinical parameters of patients. Additionally, we compared the differences between HVD and LVD. We utilized several statistical methods, including the non-parametric Mann-Whitney U test, Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression. The results indicate that SA may serve as a predictor of bone metastasis in patients with HVD. ROC curve analysis revealed a cut-off value of 56.15 mg/dL with an area under the curve of 0.767 (95% CI: 0.703-0.832, P < 0.001) for bone metastasis versus without bone metastasis and a cut-off value of 65.80 mg/dL with an area under the curve of 0.766 (95% CI: 0.644-0.888, P = 0.003) for HVD versus LVD. Notably, PCa patients with bone metastases exhibited significantly higher SA levels than those without bone metastases, and HVD patients had higher SA levels than LVD patients. In comparison to the non-metastatic and LVD cohorts, the cohort with HVD exhibited higher levels of alkaline phosphatase (AKP) (median, 122.00 U/L), fibrinogen (FIB) (median, 3.63 g/L), and prostate-specific antigen (PSA) (median, 215.70 ng/mL), as well as higher Gleason scores (> 7). Multivariate logistic regression analysis demonstrated that an SA level of > 56.15 mg/dL was independently associated with the presence of bone metastases in PCa patients (OR = 2.966, P = 0.018), while an SA level of > 65.80 mg/dL was independently associated with HVD (OR = 1.194, P = 0.048). The pretreatment serum SA level is positively correlated with the presence of bone metastases.

Quantitative vs. Qualitative SPECT-CT Diagnostic Accuracy in Bone Lesion Evaluation-A Review of the Literature.

(1) Background: Considering the importance that quantitative molecular imaging has gained and the need for objective and reproducible image interpretation, the aim of the present review is to emphasize the benefits of performing a quantitative interpretation of single photon emission computed tomography-computed tomography (SPECT-CT) studies compared to qualitative interpretation methods in bone lesion evaluations while suggesting new directions for research on this topic. (2) Methods: By conducting comprehensive literature research, we performed an analysis of published data regarding the use of quantitative and qualitative SPECT-CT in the evaluation of bone metastases. (3) Results: Several studies have evaluated the diagnostic accuracy of quantitative and qualitative SPECT-CT in differentiating between benign and metastatic bone lesions. We collected the sensitivity and specificity for both quantitative and qualitative SPECT-CT; their values ranged between 74-92% and 81-93% for quantitative bone SPECT-CT and between 60-100% and 41-100% for qualitative bone SPECT-CT. (4) Conclusions: Both qualitative and quantitative SPECT-CT present an increased potential for better differentiating between benign and metastatic bone lesions, with the latter offering additional objective information, thus increasing diagnostic accuracy and enabling the possibility of performing treatment response evaluation through accurate measurements.

Nitazoxanide inhibits acetylated KLF5-induced bone metastasis by modulating KLF5 function in prostate cancer

BackgroundCastration-resistant prostate cancer often metastasizes to the bone, and such bone metastases eventually become resistant to available therapies, leading to the death of patients. Enriched in the bone, TGF-β plays a pivotal role in bone metastasis development. However, directly targeting TGF-β or its receptors has been challenging for the treatment of bone metastasis. We previously found that TGF-β induces and then depends on the acetylation of transcription factor KLF5 at K369 to regulate multiple biological processes, including the induction of EMT, cellular invasiveness, and bone metastasis. Acetylated KLF5 (Ac-KLF5) and its downstream effectors are thus potential therapeutic targets for treating TGF-β-induced bone metastasis in prostate cancer.MethodsA spheroid invasion assay was applied to prostate cancer cells expressing KLF5K369Q, which mimics Ac-KLF5, to screen 1987 FDA-approved drugs for invasion suppression. Luciferase- and KLF5K369Q-expressing cells were injected into nude mice via the tail artery to model bone metastasis. Bioluminescence imaging, micro-CT), and histological analyses were applied to monitor and evaluate bone metastases. RNA-sequencing, bioinformatic, and biochemical analyses were used to understand nitazoxanide (NTZ)-regulated genes, signaling pathways, and the underlying mechanisms. The binding of NTZ to KLF5 proteins was evaluated using fluorescence titration, high-performance liquid chromatography (HPLC), and circular dichroism (CD) analysis.ResultsNTZ, an anthelmintic agent, was identified as a potent invasion inhibitor in the screening and validation assays. In KLF5K369Q-induced bone metastasis, NTZ exerted a potent inhibitory effect in preventive and therapeutic modes. NTZ also inhibited osteoclast differentiation, a cellular process responsible for bone metastasis induced by KLF5K369Q. NTZ attenuated the function of KLF5K369Q in 127 genes’ upregulation and 114 genes’ downregulation. Some genes’ expression changes were significantly associated with worse overall survival in patients with prostate cancer. One such change was the upregulation of MYBL2, which functionally promotes bone metastasis in prostate cancer. Additional analyses demonstrated that NTZ bound to the KLF5 protein, KLF5K369Q bound to the promoter of MYBL2 to activate its transcription, and NTZ attenuated the binding of KLF5K369Q to the MYBL2 promoter.ConclusionsNTZ is a potential therapeutic agent for bone metastasis induced by the TGF-β/Ac-KLF5 signaling axis in prostate cancer and likely other cancers.

Preliminary Study on Establishing a Heart Rate Variability–Based Method for Objectively Evaluating Bone Metastasis Pain

<h3>Purpose/Objective(s)</h3> No standardized method objectively evaluates cancer pain. In this case, measuring heart rate variability (HRV) using fluctuations in heartbeat interval (statistical software) may be useful because pain activates sympathetic nerve activity. Fluctuation analysis of RRI frequency demonstrates a high frequency (HF) and low frequency (LF) component. HF represents parasympathetic nerve activity, while the LF-to-HF ratio (LF/HF) represents sympathetic nerve activity. We hypothesized that HRV measurement is an effective and objective evaluation tool for bone metastases pain. <h3>Materials/Methods</h3> This prospective study enrolled patients receiving radiotherapy for painful bone metastases. Pain was assessed using a numerical rating scale (NRS), and anxiety and depression were evaluated based on Hospital Anxiety and Depression Scale (HADS). The average, maximum, and minimum NRS scores were separately evaluated. Autonomic and physical activities were evaluated by measuring HRV through a wearable device (Union Tool Co., Tokyo, Japan). Through a three-dimensional conformal technique, radiotherapy was delivered as 20–30 Gy doses in 5–10 fractions. Alternatively, stereotactic body radiotherapy (SBRT) was delivered as doses of 24 Gy in two fractions or 35 Gy in five fractions. In principle, the values of NRS, HADS, and RRI were obtained upon starting, completing, and 3–5 weeks after radiotherapy. RRI were obtained over approximately 24 h. <h3>Results</h3> Between July 2020 and July 2021, 11 patients were enrolled. The median age was 65 years (range: 50–83 years). Seven of 11 patients were treated with SBRT. We analyzed 27 NRS scores and heart rate interval measurements and 26 HADS scores. The median, average, maximum, and minimum NRS scores were 5 (range: 2–10), 6 (range: 2–10), and 3 (range: 0–8), respectively. HADS-assessed median anxiety and depression scores were both 8 (ranges: 1–13 and 2–21 respectively), and mean HF and LF/HF values were 0.52 ms² (SD: 1.66 ms²) and 2.45 (SD: 1.20), respectively. For all samples, NRS score had no significant relationship with mean LF/HF or HF (p = 0.66 and p = 0.74, respectively). However, for samples with NRS scores ≥ 4, NRS score had a significant association with LF/HF (p = 0.03). Heart rate during physical activity was significantly higher than the resting heart rate; however, mean resting LF/HF was significantly higher than LF/HF during physical activity. During rest, mean LF/HF was not associated with NRS score across all samples, including those with NRS scores ≥ 4 (p = 0.61 and p = 0.49, respectively). In samples excluding those with NRS scores < 4 and HADS depression scores ≥ 7, NRS score had a weak significant relationship with mean LF/HF (p = 0.07). <h3>Conclusion</h3> HRV measurements could objectively evaluate bone metastases pain. However, the effects of mental status, such as depression, on LF/HF affects HRV in cancer patients with mild pain.

Evaluating prostate cancer bone metastasis using accelerated whole-body isotropic 3D T1-weighted Dixon MRI with compressed SENSE: a feasibility study.

The study aimed to assess the efficiency of whole-body high-resolution compressed sensing-sensitivity encoding isotropic T1-Weighted Dixon (CSI-T1W-Dixon) scans in evaluating bone metastasis. Forty-five high-risk prostate cancer patients with bone metastases were enrolled prospectively and underwent whole-body MRI sequences, which included the following: pre- and post-contrast CSI-T1W-Dixon and conventional multi-planar T1-Weighted Dixon (CMP-T1W-Dixon) (coronal, sagittal, and axial scans), short tau inversion recovery (STIR), and DWI. Comparison between the CMP-T1W-Dixon and CSI-T1W-Dixon images was done for the subjective image quality, the quantitative contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR). Furthermore, the diagnostic performance based on per-lesion and per-patient basis utilizing non-contrast T1-weighted (T1)/T1+ contrasted T1-weighted (T1C)/T1 + T1C + STIR + DWI sequences was compared between the CSI-T1W-Dixon and CMP-T1W-Dixon methods using reference standards (combining biopsy data and 6-month imaging follow-up). The CSI-T1W-Dixon images produced fewer image artifacts in the axial and coronal planes compared to the CMP-T1W-Dixon images. Also, the CSI-T1W-Dixon images provided better a CNR in fat-only images of all three planes and water-only images of the axial plane (p < 0.05). The CSI-T1W-Dixon showed a higher sensitivity than the CMP-T1W-Dixon techniques in analyzing T1-only images on a per-lesion basis (82.7% vs. 53.8% for sensitivity, p = 0.03). On a per-patient basis, no difference was found in the diagnostic capacity between the CSI-T1W-Dixon and CMP-T1W-Dixon sequences either alone or in combinations (p = 0.57-1). High-resolution CSI-T1W-Dixon with higher image quality and diagnostic capacity can replace the CMP-T1W-Dixon method in evaluating bone metastasis in clinical practice. • Compressed sensing isotropic acquisition for 3D T1-weighted Dixon images can improve the image quality with fewer artifacts compared to the anisotropic multiplanar acquisition. • Compressed sensing isotropic acquisition can save 67% of scanning time compared to anisotropic multiplanar acquisition. • Compressed sensing isotropic 3D T1-weighted Dixon images can offer better diagnostic performance with higher sensitivity compared to anisotropic multiplanar images.

Bone-specific response according to MDA criteria predicts immunotherapy efficacy among advanced non-small cell lung cancer (NSCLC) patients

PurposeThe presence of bone metastasis at baseline has been associated with dismal prognosis under immunotherapy in advanced non-small cell lung cancer (NSCLC). Response Evaluation Criteria in Solid Tumors (RECIST) criteria may be limited for bone-specific response evaluation. Whether their assessment through MD Anderson (MDA) criteria predict immunotherapy efficacy is unknown.Materials and methodsWe conducted a single-center retrospective study to assess the use of MDA criteria in evaluating bone metastasis in NSCLC treated with immunotherapy. Radiological imaging were reviewed to classify bone lesions as osteolytic, osteoblastic, or mixed. Bone response to treatment data was classified according to MDA criteria.Results222 patients received single-agent immunotherapy. The presence of bone metastasis increased the risk of death both in the univariate (HR: 1.46, 95% CI, 1.05–2.03, p = 0.024) and in the multivariate model (HR: 1.61, 95% CI, 1.10–2.36, p = 0.015). According to MDA criteria, 57.3% of patients had progressive disease as best response, 29.5% stable disease, 11.4% partial response and 1.6% complete response. Bone-specific objective response was associated with a significantly increased median overall survival (11.3 vs. 3.1 months, p = 0.027) and longer median progression-free survival (6 vs. 2.1 months, p = 0.056). The median time to bone failure (TBF) was 2.4 months (IQR, 1.67–3.0). In 25.7% of cases, TBF was shorter than progression-free survival according to RECIST 1.1 criteria. TBF was positively correlated with overall survival (HR = 0.73, p = 0.00019).ConclusionsMDA criteria represent a reliable tool in assessing bone-specific response, offering a more accurate evaluation with the aim to earlier predict survival outcomes or treatment failure compared to RECIST criteria for advanced NSCLC patients receiving immunotherapy.

Therapy-induced bone changes in oncology imaging with 18F-sodium fluoride (NaF) PET-CT.

18F-Sodium fluoride (18F-NaF) is a PET tracer that is mostly used in the evaluation of bone metastasis in oncology cases. Recently, 18F-NaF PET/CT is gaining wide popularity owing to its higher sensitivity over the other conventional bone tracer with higher and rapid single-pass extraction, negligible plasma protein binding, rapid blood, and renal clearance. In the era of constant evolution of cancer therapy regimens, considerable bone health impact is seen in the form of avascular necrosis, insufficiency fractures, among others. A significant number of these therapy-induced changes show high bone turnover and thereby 18F-NaF accumulation, mimicking metastatic lesions. This article summarizes and illustrates the pattern and morphological features of 18F-NaF PET/CT findings in these changes in the context of clinical and therapeutic history.

Application of SPECT Combined with CT and MRI in Malignant Tumors Clinical Value in the Diagnosis of Bone Metastasis

Introduction: Bone is the most common site of hematogenous metastasis of malignant tumors. Patients with bone metastasis can have a series of bone related adverse events, which seriously affect the quality of life and survival time of patients. Imaging examination is the main means of clinical diagnosis and evaluation of bone metastasis. Aim of the Work: To evaluate the value of single-photon emission computerized tomography (SPECT) combined with CT and MRI in the diagnosis of bone metastasis of malignant tumors. Subjects and Methods: Eighty patients with bone metastasis from malignant tumors who were admitted to Affiliated Hospital of Chengde Medical College were selected from March 2019 to June 2021. They underwent bone scan with SPECT imaging, CT and MRI separately. The distribution of bone metastasis from primary tumors as well as efficacy of the above three detection methods for bone metastasis was analyzed. Results: A total of 464 lesions were detected by SPECT and CT in the same scanning field, with SPECT detection rate of 92.5% (429/464) and CT detection rate of 77.8% (361/464) (P P P P < 0.05). Conclusion: SPECT may be the preferred screening modality for uspected bone metastases, and when combined with CT and MRI, it can clarify the regional distribution of bone metastasis from malignant tumors and improve the sensitivity, specificity and accuracy of diagnosis with high clinical significance.

Diagnostic Performance of CT Compared to PET/CT in Evaluating Bone Metastasis - An Initial Experience from Nepal

Introduction: Bone metastasis is frequently encountered in different cancers. Computed tomography (CT) is commonly used to detect bone metastasis. Positron emission tomography (PET) has only recently been introduced in Nepal. Various studies have shown PET/CT to be superior to CT alone in identifying bone metastasis. This study aims to compare the utility of CT scan compared to F-18 FDG PET/CT for detecting bone metastasis in common non-hematological malignancies. Methods: The medical records of cancer patients referred to us between from September 2019 to April 2020 were reviewed retrospectively. Two radiologists and two nuclear medicine physicians read the CT and PET/CT scans respectively, performed as part of the same study. Results were categorized as positive, negative of equivocal. The sensitivity, specificity and accuracy of CT alone was evaluated compared to PET/CT. Results: A total of 365 patients were included in the study. Out of 365 patients, bone metastasis was detected in 53 patients (14.5%). CT alone was true positive in 40 patients, true negative in 311 patients, false positive in 1 patient and false negative in 13 patients. (5 equivocal cases considered as negative). On per-patient analysis, CT alone when compared to PET/CT had sensitivity, specificity, and overall accuracy of 75.4%, 99.6% and 96.1% respectively for detection of bone metastasis. Conclusions: Our study highlights that metabolic alteration in bone metastasis are identified by F-18 FDG PET/CT even before morphological changes are apparent on CT. Further, F-18 FDG PET/CT is extremely helpful if CT findings are equivocal for bone metastasis.

747 IS 99MTC BONE SCINTIGRAPHY NECESSARY IN THE PREOPERATIVE WORKUP FOR PATIENTS WITH POTENTIALLY RESECTABLE ESOPHAGEAL SQUAMOUS CELL CANCER?

Abstract 99mTc bone scintigraphy(BS) is still the most widely used method to evaluate bone metastasis in China. The aim of this study was to investigate the necessity of the 99mTc bone scintigraphy in the preoperative workup for patients with potentially resectable esophageal squamous cell cancer (ESCC,cT1-4aN0–3). Methods This was a prospective cross-section clinical trial (ChiCTR1800020304). There were a total of 471 patients who were diagnosed ESCC in Thoracic Surgery Clinic from October 2018 to September 2020. Of these 471 patients, 385 patients with cT1-4aN0–3 who were potentially candidates for surgical resection were consecutively enrolled into the study. BS was performed preoperatively. The treatment strategy could be changed if the bone metastasis was confirmed. The primary endpoint was the incidence rate of the treatment regimen being changed because of bone metastasis. The secondary endpoint was the rate of positive BS findings. Results In all 385 patients, there are only 2(0.5%) patients changed their treatment regimen because of bone metastasis proved by BS. The rate of positive BS findings is 1%. The number of patients with false positive and false negative was 2(0.5%) and 2 (0.5%), respectively. The BS diagnostic performance for bone metastasis was as follows: sensitivity, 50%; specificity, 99.5%; positive predictive value, 50%; negative predictive value, 99.5% and accuracy, 99.0%. There were no significant difference of bone metastasis among the Age, Sex, Tumor location and Clinical stage. Conclusion 99mTc bone scintigraphy is unnecessary in the preoperative workup for patients with potentially resectable esophageal squamous cell cancer.

Clavicular Metastasis as an Initial Presentation of Papillary Thyroid Cancer

Background: Papillary thyroid cancer (PTC) metastases to the clavicular bone is rare. While the lung is considered the most common site of metastases from thyroid malignancy, osseous metastases, if seen, are usually observed at sites such as humerus, pelvis, radius, and scapula. Clinical Case: A 44-year-old man presented with an enlarging right neck mass for six months after light trauma to that area. Other than mild pain in the described area, the patient reported 20 lbs of weight loss. Initial x-ray revealed a large soft tissue density mass that extended to the midline of the right proximal clavicle. Soft-tissue neck ultrasound noted a 5.4 x 3.6 cm mass extending from the thyroid with findings of increased vascularity and calcification. CT scan of the neck depicted the extension of the mass into the adjacent sternoclavicular junction with osteolysis of the middle third of the clavicle as well as the superior aspect of the sternal body. A fine needle aspiration of the mass revealed thyroid neoplasm with follicular features and positive immunostaining consistent with thyroid carcinoma. Chest CT showed invasion into the right proximal clavicle, tracheal deviation and extension into the mediastinum. The patient underwent a composite resection of the tumor, including a segmental osteotomy of approximately two-thirds of the medial clavicle. Post surgically the patient’s serum calcium was low at 7.9 mg/dL with a concurrently low PTH of 9 pg/mL and a low 25-hydroxyvitamin D of 16.8 ng/mL. Thyroglobulin was markedly high at 15655.0 ng/mL (confirmed on dilution), and thyroglobulin antibody < 1.0 IU/mL. Pathology report confirmed PTC with extra-thyroidal extension and involvement of clavicle (staged pT4a pN0), however margins and lymph nodes were negative for carcinoma with further genomic findings showing positive KRAS mutation. The patient’s post-operative course was complicated by a large expanding left neck hematoma after a fall; he was immediately readmitted with the hematoma subsequently safely evacuated. Levothyroxine has been held at this time with plans for radioactive iodine treatment eight weeks after surgery. Conclusion: Bone metastases from differentiated thyroid cancer is rare, especially clavicular metastasis arising from PTC. Bone scintigraphy, x-ray and fine needle biopsy are some of the widely utilized methods employed in the evaluation of bone metastasis in the setting of thyroid malignancy. The prospect of recovery is generally favorable in cases of bone metastases, however various factors can affect prognosis and long-term outcomes. Reference: Krishnamurthy A. Clavicle metastasis from carcinoma thyroid- an atypical skeletal event and a management dilemma. Indian J Surg Oncol. 2015;6(3):267-270. doi:10.1007/s13193-015-0387-y

Superscan: Superiority of xSPECT/CT over OSEM SPECT/CT in bone scans of prostate cancer patients.

Prostate cancer is one of the most common cancers affecting men. Bone scan is part of the staging modality commonly used to evaluate bone metastasis. A bone scan with diffused increased skeletal tracer uptake relative to soft tissue, combined with faint renal activity is known as a superscan. However, a primary concern are false negatives associated with bone scans, where diffuse metastasis is indistinguishable on superscans. In this study, we performed xSPECT/CT Bone and standard OSEM SPECT/CT reconstruction algorithm in ten prostate cancer patients with high PSA levels, where they initially seem relatively unremarkable on planar images. All patients with extensive bone metastases showed either relatively unremarkable scans or did not demonstrate the true extent of metastatic burden as seen on planar images. Uptake was further confirmed by the correlative diffuse bone lesions on CT images. Our reports also indicated that xSPECT/CT reconstructed images were far superior in delineating focal areas of osteoblastic bone metastasis, when compared with whole body planar images or SPECT/CT images. The extent of metastatic evidence is delineated with excellent clarification by xSPECT/CT images. We propose that whole body xSPECT/CT image reconstruction, or at least SPECT/CT, should be performed in patients with high PSA levels, along with planar imaging, to improve diagnostic accuracy of bone scans in prostate cancer staging.

Evaluation of bone metastasis and prognosis of prostate cancer with bone metastasis during standard hormonal therapy and chemotherapy: A report of PROSTAT-BSI multicenter registry in Japan.

215 Background: Quantitative evaluation of the change of bone metastasis (bMet) has not been clearly defined during treatments in prostate cancer (PCa). As therapeutic effects of bMet have become quantified with scintigraphic bone scan index (BSI), we performed a nation-wide observational prospective study in patients who were treated by hormonal therapy (HTx) or chemotherapy (CTx). Methods: A total of 237 patients were recruited at 30 hospitals in Japan, and this report summarized baseline demographics and prognosis of 203 patients. All had bMet and underwent either standard HTx (group H) or docetaxel CTx (group C). Bone scans were performed with 99mTc-MDP. Patients were followed up for 3 years, and changes in biochemical and tumor markers during HTx and CTx were recorded in addition to skeletal-related events, recurrence, and death. Results: The basic characteristics of the patients (n=203) at the time of registration during December 2016 were as follows: mean age 71 ± 8 years; median BSI calculated on-site 3.0 ± 3.2% and median PSA was 265 ng/mL (22-2923 ng/mL) and 33 (3-537 ng/mL), for Group H and C (p=0.0014), respectively. BSI was comparable (H: 3.0 ± 3.4 vs C: 3.0 ± 2.8%, p=n.s.) between the two groups. A total of 54 patients (24%) died from PCa. BSI flare defined as increase at 3 months and decrease at 6 months was 13% and 31% (p&lt;0.0069) for Groups H and C, respectively. When patients were classified into three groups with BSI &lt;0.9 (low), 0.9-3.3 (intermediate), and &gt;3.3% (high). Kaplan-Meier Survival analysis showed that mortality at 1100 days was 8%, 16%, and 35% for Group H (p=0.0097), and 50%, 55%, and 65% for Group C (p=ns) for the low, intermediate and high BSI group, respectively. In addition, patients who showed BSI decline &gt;20% until 6 months showed better prognosis than those who did not (p&lt;0.0001 and p= 0.038 and for Group H and C, respectively). Conclusions: The data of PROSTAT-BSI showed that BSI could be a good biomarker for prognosis in both Groups H and C, in particular for prognostic stratification of patients indicated for HTx. Six-month response of BSI by &gt;20% indicated better prognosis in both groups. Clinical trial information: UMIN000007858.

Whole-Body MRI with Diffusion-Weighted Imaging in Bone Metastases: A Narrative Review.

Whole body magnetic resonance imaging (MRI) with diffusion-weighted imaging (WB-MRI-DWI) is currently emerging as a diagnostic technique in the evaluation of bone metastases from breast, prostate, lung, thyroid, and melanoma tumors. The most relevant articles regarding the detection of solid tumor bone metastases with MRI have been reviewed and cited. The imaging methods currently used in the detection of bone metastases are bone scintigraphy, computed tomography (CT), and positron emission tomography (PET/CT) with 2-deoxy-2-[fluorine-18] fluoro-d-glucose (18F-FDG PET/CT). WB-MRI-DWI allows qualitative and quantitative evaluation of focal lesions through signal intensity evaluation on DWI images and the reconstruction of the apparent diffusion coefficient (ADC) map. In prostate and breast cancer, WB-MRI-DWI is useful in assessing the response of bone lesions to therapy and to detecting early non-responders, while in lung cancer the method shows a similar sensitivity to 18F-FDG PET/CT in the detection of bone metastases. In bone metastases of thyroid tumors and melanoma, the WB-MRI-DWI shows a higher sensitivity when compared to 18F-FDG PET/CT. With a standardization of the WB-MRI-DWI protocol, this method seems to play an important role in the diagnosis of bone solid tumor metastases.

Metabolic imaging in the response assessment of patients treated with 223Ra. What should be

Controversy between current clinical and imaging guidelines about needing to assess response during 223Ra treatment with diagnostic imaging exists, with very restrictive recommendations regarding the use of metabolic imaging. This review summarizes the current evidence and discusses some aspects related to the challenging response evaluation of bone metastases in patients with castration-resistant prostate cancer.

DIAGNOSTIC IMAGING STANDARDS FOR BONE METASTASES

The purpose of the study was an attempt to create universal criteria for the diagnostic imaging of bone metastases allowing biopsy to be avoided. Material and methods. Scans from 90 patients with verified primary malignant tumors and focal bone lesions in the (n=278) were analyzed. The minimal size of the focal bone lesion was 1 cm. All patients underwent multiparameter magnetic resonance imaging with a modified scanning protocol and single-photon emission computed tomography combined with computed tomography. Diagnostic evaluation was performed before starting treatment, 1 month after starting therapy, then every 3 months for 1 year. Results. The original «principle of 8 diagnostic elements» had been created, allowing the assessment of the main pathological conditions and processes occurring in bone structures. Based on the analysis and statistic processing of 236 foci of metastatic lesion, the diagnostic informative value of each of the imaging modalities and the algorithm as a whole were assessed, and the reference values were determined. This approach allowed the accuracy of early diagnosis to be improved due to a more reliable evaluation of bone metastases at an early stage, thus reducing or completely avoiding additional biopsies.

Abstract P5-05-06: Development of advanced pre-clinical in vivo models of metastatic breast cancer

Abstract Backgrounds: The fact that we continue to lose 40,000 women with breast cancer every year in the US despite the recent advance in basic research clearly demonstrate disconnect in translation of basic research findings to clinic. This is largely due to lack of appropriate animal model that mimic clinical conditions for preclinical studies that result in high failure rate of clinical trials. To date, we had established many syngeneic mouse models, which are not free from limitations; 1) few clinically relevant animal models with bone metastasis have been established, 2) syngeneic mouse model cannot address human cancer genomics and tumor heterogeneity. Patient-Derived Xenograft (PDX) model has emerged as pre-clinical model to address these issues, however, it suffers low tumor take rate of around 20-40%, and lack metastatic model. Here, we describe development of orthotopic implantation, and bone and liver metastatic breast cancer mouse models to overcome these limitations. Methods: 1) 4T1.2-luc3 cells that has metastatic potential to the bone were orthotropically inoculated as a syngeneic mouse model, imaged with IVIS and MRI. 2) Patient tumor tissues of 1mm(3) were implanted surgically into dorsal subcutaneous space (SQ), or orthotropically into mammary fat pat #2 and #4 (MFP). Results: 1) We established a syngeneic breast cancer bone metastasis model. Primary tumors were surgically resected days after 4T1.2-luc3 cells were orthotopically implanted under direct vision. Removal of primary tumor allowed bioluminescent visualization and quantification of bone metastasis by IVIS. We found that MRI was effective in evaluating bone metastasis and bone related events in these mice. MRI allows differentiation of bone metastasis from metastasis to the surrounding organs with bone destruction image, whereas conventional bioluminescence imaging shows only existence of cancer cells. 2) The overall tumor take rate of the tumor in PDX model was 46.0% (74/161 implantation site). Take rate from triple-negative breast cancer tumors was 56.1% (74/132), on the other hand, that from ER positive tumors was 0% (0/39). Tumor take rate was significantly better in MFP implantation than SQ (39.5%, 30/76 vs 51.2%, 44/85, p&amp;lt;0.01). Tumor weight were significantly heavier in MFP compared to SQ (0.072g vs 0.328g, p&amp;lt;0.00001). With more passage, the difference in tumor weight between SQ and MFP was significantly increased(p&amp;lt;0.0001). Finally, we developed a PDX breast cancer liver metastasis model by surgically implanting tissue fragment into liver using direct vision technique. We found MRI to be very useful as a living imaging modality to evaluate cancer progression in the deeply located metastatic sites of PDX models. Conclusions: We have established orthotropic syngeneic breast cancer bone metastasis model as well as improved breast cancer PDX model with synchronous liver metastasis utilizing MRI. Our novel models could be powerful tools for preclinical studies. Citation Format: Okano M, Kawaguchi T, Okano I, Katsuta E, Takabe K. Development of advanced pre-clinical in vivo models of metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-05-06.

Bone and calcium metabolism associated with malignancy. Bone metastasis of prostate cancer:overview of clinical features and treatments.

Bones are the most frequent sites in patients with progressive prostate cancer. Spinal column and pelvic bone are vulnerable for metastasis, and osteoblastic lesions are frequently observed. Imaging evaluation is performed using bone scintigrapy with 99mTc, CT or MRI. Extent of disease is categorized as EOD score, and it is still used for evaluation of bone metastasis in clinical trials. Clinical guidelines recommend the uses of bone modifying agents including zoledronic acid and denosumab for bone metastasis in patients with castration-resistant prostate cancer. New androgen targeted agents, enzalutamide and abiraterone, or taxans, docetaxel and cabazitaxel, show clinical efficacy for bone metastasis of prostate cancer. Recently, metastasis free survival(MFS)has been approved as a primary endpoint for nonmetastatic castration-resistant prostate cancer. For this category, enzalutamide and apalutamide have been approved for patients with nonmetastatic castration-resistant prostate cancer. Treatment and follow-up strategy is now dramatically changed in the area of bone metastasis of prostate cancer.