Osseous Metastatic Lesions Research Articles

Spinal Diffuse Midline Glioma H3 K27M-Altered: Report of a Rare Tumor with Extracranial Skeletal Metastases and Review of Literature.

Diffuse midline glioma, H3 K27-altered is a rare and aggressive pediatric brain tumor with a grim prognosis. Diffuse midline glioma is characterized by specific molecular alterations, including H3 K27 mutations, and involves deep midline structures such as the brainstem, cerebellum, spinal cord, and thalamus. These tumors present with a classic triad of symptoms and have limited surgical options due to their challenging locations. Extra-neural metastases are an unusual occurrence in diffuse midline glioma and have been rarely described. Here we report a 17-year-old girl with spinal diffuse midline glioma, H3 K27M-mutant, who presented with multiple metastatic osseous lesions confirmed on biopsy of the thoracic vertebral lesion. Due to the rapid disease progression, the patient was recommended palliative therapy. Extra-neural metastases in diffuse midline glioma are rare, with only 16 reported patients, and no standard therapy exists. An accurate and early diagnosis is necessary to develop a personalized plan of treatment. Further research is needed to gain insights into the molecular pathology of diffuse midline glioma, H3 K27-altered, and improve the quality of life and the outcome of patients with this deadly disease.

Osseous tumors of the foot, ankle, and lower leg: a cross-sectional observational study analysing 288 cases

BackgroundOsseous tumors of the foot and ankle are rarely encountered in general orthopaedic practice and represent only 3 % of osseous neoplasms. It can be difficult to distinguish between benign and malignant lesions, leading to misdiagnosis. Delays in diagnosis are the main cause of litigation in sarcoma of the extremities. Poor understanding of how sarcomas present in this region can lead to inappropriate initial procedures, limiting options for limb salvage and increasing rates of local recurrence. Our aim is to improve understanding of these rare tumors to reduce misdiagnosis and decrease the occurrence of inappropriate or unwarranted procedures. MethodsWe retrospectively analysed a prospectively maintained database of 288 new referrals to the West of Scotland regional musculoskeletal oncology service for osseous lesions of the foot, ankle and lower leg over a 10-year period. An analysis of patient demographics, presentation, anatomical location, diagnosis, classification, management and outcomes was performed. ResultsOf all new referrals, 52.4 % were diagnosed with primary benign osseous tumors, 8.7 % with primary malignant osseous tumors, 9.7 % with metastatic osseous lesions, and 29.2 % pseudotumors. The most common primary benign tumor in our population was osteoid osteoma (18.5 %), primary malignant tumor was osteosarcoma (32 %) and metastatic osseous lesions were from small cell lung cancer primary (14.3 %). In the foot and ankle, malignant bone tumors most commonly presented in the distal tibia and fibula (20 %). Rest pain was the most common symptom at presentation in all groups, followed by swelling. The average duration of symptoms was 5 months for malignant lesions before primary referral. ConclusionBone tumors in the foot and ankle remain a diagnostic challenge. We hope to have increased understanding of these rare lesions and have recommended a management protocol in order to reduce the number of inappropriate procedures performed, optimising clinical outcomes and reducing the cost of litigation to healthcare services. Level of EvidenceLevel III- Cross-sectional observational study

18 F FDG PET/CT versus 99m Tc MDP Bone scintigraphy in imaging of metastatic osseous disease in breast cancer patients; Solving the discrepancies in light of serum markers.

To assess the performance of 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) versus 99m Tc MDP bone scan in assessment of metastatic osseous disease in breast cancer patients in relation to serum markers. We reviewed PET/CT studies and bone scans for 37 patients (mean age of 55.38 ± 13.08 years) with metastatic breast cancer to bone. To assess metastatic osseous burden, we used semiquantitative scores derived from PET/CT (PMS) and bone scans (BMS). We used McNemar test to compare lesion detection between both modalities and receiver operator characteristic analysis to define the cutoff value of serum CA 15-3 that best predicts additional value for PET/CT over bone scan. In 13 patients (35.1%), more lesions or higher-intensity lesions were detected on PET/CT, while only 4 patients (10.8%) had more prominent lesions on bone scans ( P = 0.049). Additional lesions seen on PET/CT are predominantly osteolytic or medullary (early phase). Most lesions with higher uptake on bone scans appear sclerotic (late phase). CA 15-3 was positively correlated to PMS ( r = 0.386; P = 0.018) but not to BMS ( r = -0.027; P = 0.874). However, serum alkaline phosphatase was positively correlated to both PMS ( r = 0.389; P = 0.017) and BMS ( r = 0.363; P = 0.027). CA 15-3 value of >47 U/ml best predicted additional findings on PET/CT compared to bone scans (area under the curve = 0.708; P = 0.0261). FDG PET/CT detects metastatic osseous lesions during an earlier phase. A higher CA 15-3 predicts a higher metastatic burden on PET/CT but not on bone scan. Bone scans are less specific, likely by missing early lesions and detecting persistent uptake in healing sclerotic lesions.

Value of PET/CT Scanning in Detection of Osseous and Marrow Metastatic Lesions in Cancer Patients

Abstract Background Early diagnosis of cancer remains to be of paramount importance to maximize a patient’s long-term survival and reduce various neurological, hematological, and orthopedic complications that may arise. Skeletal metastasis (SM) is a frequently encountered and important complication of cancer which can lead to intolerable pain. Objectives The goal of the study was to illustrate the value of combined 18F-FDG PET/CT over isolated CT for detection of osseous metastases in cancer patients. Patients and Methods The study included 75 patients. 18F-PET/CT scans were performed. In this study, a lesion-based analysis was performed in detailed retrograde manner. Statistical analysis including specificity, Sensitivity, negative predictive value (NPV) and positive predictive value (PPV) of each of these modalities were calculated. A final diagnosis of metastasis was confirmed by biopsy. Results Combined PET-CT examination is highly sensitive imaging modality in detection of early bone marrow metastatic lesions which are not yet evident on conventional CT study. Conclusion Combined 18-F FDG PET/CT significantly improves the sensitivity and specificity of isolated CT for the detection of osseous and bone marrow metastases. Thus, it adds a significant value that can detect lesions and consequently start a treatment course and improve the overall outcome of the disease process.

Evaluating Treatment Response in Breast Cancer: A Case Report on Static Metastatic Disease on Bone Scans

Background: We report a case of a 54-year-old female patient with carcinoma of the left breast with persistent methylene diphosphonate (MDP) uptake in sclerotic osseous lesions. These lesions were finally declared treated osseous metastatic lesions due to non-avidity on the F18 FDG PET-CT scan, normalization of CA-15.3, and resolution of bone pains. To the best of our knowledge, this has not been reported previously. Case presentation: A 54-year-old woman with persistent backache was referred for further evaluation by a Tc99m MDP bone scan. A Tc-99mmMDP bone scan showed wide-spread skeletal metastatic disease. Magnetic resonance imaging (MRI) showed extensive marrow disease involving the spine and iliac bones. A bone marrow biopsy revealed metastatic carcinoma with a tumor phenotype favoring breast primary. On further workup, the patient was diagnosed with invasive ductal carcinoma of the left breast and was treated with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors along with hormone therapy and bisphosphonates, followed by radiation therapy for bone metastasis. The skeletal metastatic disease remains static on three consecutive Tc99m MDP bone scans, despite the clinical improvement and decreased tumor marker levels. The F18-FDG-FDG-CT scan done for monitoring treatment response revealed multiple non-avid sclerotic osseous lesions, favoring treatment response. The patient was continued with the same treatment, and a follow-up Tc99m MDP bone scan after 6 months revealed no interval change in the reported lesions compared to the initial scan. However, a synergistically performed F18 FDG PET-CT scan again showed multiple non-avid sclerotic osseous lesions suggestive of treated metastasis. Conclusion: This case highlights the importance of 18F-FDG PET-CT in evaluating the treatment response, especially in patients with symptomatic improvement and falling tumor marker levels with static disease on repeated Tc99m MDP bone scans.

Treatment Efficacy Outcomes Combining Dual Checkpoint Immunotherapy with Ablative Radiation to All Sites of Oligometastatic Non-Small Cell Lung Cancer: Survival Analysis of a Phase IB trial

Aggressivelocal treatment to a limited number of metastatic sites in patients with oligometastatic NSCLC increases progression free survival (PFS) and overall survival (OS). Prior studies have shown the safety of combining high dose stereotactic body radiation therapy (SBRT) with single agent anti-PD1/PD-L1 therapy. Here, we report secondary survival endpoint outcomes from a phase Ib clinical trial investigating the safety of combining ablative, high dose radiation with dual checkpoint, anti-CTLA-4 and anti-PD-L1 immunotherapy for patients with oligometastatic NSCLC. Patients with up to 6 sites of extracranial metastatic disease were eligible for trial enrollment. All sites of disease were treated with stereotactic body radiation therapy to a dose of 30 - 50 Gy in 5 fractions. Dual checkpoint immunotherapy was started 7 days following completion of radiation utilizing anti-CTLA-4 (Tremelimumab) and anti-PD-L1 (Durvalumab) immunotherapy for a total of four cycles followed by durvalumab alone until dose limiting toxicity or progression was observed. Primary toxicity outcomes were previously reported. Progression free and overall survival was analyzed using Kaplan Meier statistical methods. Fifteen patients were treated with SBRT and received at least one dose of dual agent immunotherapy per protocol. The median follow up was 43 months. The median number of extracranial metastatic sites was 2. Seven patients had 3 or more sites of extracranial disease. The most commonly treated sites were separate metastatic pulmonary lesions or osseous metastatic lesions. Median progression free survival (PFS) was 42 months and median overall survival (OS) was 48 months. Seven patients remain alive without evidence of progressive disease. Prior history of brain metastases was associated with significantly worse PFS (Median PFS 4 months vs 42 months, HR 6.1 (95% CI 1.6 - 37.0) p = 0.0248), but no difference in OS (Median OS 24 vs 42 months, HR 1.9 (95% CI 0.3 - 10.4). Ablative SBRT radiation to up to 6 sites of disease followed by dual checkpoint immunotherapy in oligometastatic NSCLC resulted in a favorable progression free survival (42 months) and overall survival (48 months) compared to historical controls. These findings suggest potential benefit to patient outcomes compared to immunotherapy or radiation alone in this patient population and warrant further investigation.

Role of 68Ga-PSMA PET/CT in Initial Staging of Prostate Cancer and Correlation with PSA and Gleason Score

Background Prostate cancer is the second most common male malignancy. Its prognosis depends on the tumor stage as well as its aggressiveness; expressed histopathologically by Gleason scores. Furthermore, optimal patient management depends on the tumor stage. 68Ga PSMA PET/CT has a wide spectrum of uses in prostate malignancy, some of them are comprehensively studied while others are still under investigation. The most widely accepted use is the accurate initial staging of cancer prostate as well as predicting the long-term outcome, with SUVmax being a promising prognostic parameter correlating significantly with other established prognostic parameters, including the Gleason score and the PSA levels. Objective To evaluate the role of 68GA- PSMA PET/CT in initial staging of prostate cancer and correlate with PSA level and Gleason score. Methods A prospective descriptive study over the course of 6 months. It included patients with pathologically proven prostate cancer referred for a PSMA PET/CT scan for initial staging without any treatment or interventions. Results 68Ga-PSMA PET/CT scans of 36 patients were evaluated for local staging (primary prostatic lesions, extra-prostatic spread, and seminal vesicle invasion), regional nodal staging, and metastatic spread (extra-regional lymph nodes, osseous lesions, and visceral lesions). PET/CT findings as well as the SUVmax of the most avid lesions were correlated with PSA level, Gleason scores, as well as Gleason grade risk groups. A statistically significant relationship was found between PSA level and SUVmax of prostatic lesion as well as that of the most avid metastatic regional lymph node, the presence of extra-regional lymph nodal spread, the presence of osseous metastatic lesions, the presence of seminal vesicle invasion, extra-prostatic extension, and the presence of PSMA-avid regional lymph nodal spread. On the other hand, a statistically significant relationship was found between Gleason scores and the presence of regional lymph nodal spread and osseous metastatic lesions. Lastly, a statistically significant relationship was found between Gleason grading risk groups and the presence of regional lymph nodal spread and osseous metastatic lesions. Conclusion 68Ga-PSMA PET/CT is a powerful staging and stratifying tool for the majority of prostate cancer patients, being significantly correlated with PSA level and Gleason scores. However, patients with low PSA scores still pose a dilemma as they showed significantly low PSMA uptake, rendering the use of 68Ga-PSMA PET/CT for staging in such patients controversial. 68Ga-PSMA PET/CT based imaging findings should ideally be supported with histopathological documentation and/or follow-up imaging results in order to confirm the nature of detected lesions and help establish accurate sensitivity and specificity of 68Ga-PSMA PET/CT.

FDG PET/CT and NaF PET/CT imaging quantification of osseous metastatic lesions in patients with metastatic genitourinary (mGU) cancer and their association with survival outcomes.

e16573 Background: Identifying osseous lesions and quantifying their response to therapy is challenging. 18F-fluorodeoxyglucose (FDG) and 18F-sodium Fluoride (NaF) PET/CT are both functional imaging modalities with increased sensitivity and specificity for detecting osseous lesions. This study analyzed the association of baseline FDG PET/CT and NaF PET/CT semi-quantitative parameters of bone lesions with or without additional visceral metastasis with survival for patients (pts) with non-prostate mGU malignancies treated on a phase I study with Cabozantinib (Cabo), Nivolumab (Nivo) +/- Ipilimumab (Ipi). Methods: Patients underwent sequential FDG PET/CT and NaF PET/CT scans at baseline. Semi-quantitative imaging parameters were measured including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for FDG and fluoride uptake tumor volume (FTV) and total lesion fluoride uptake (TLF) for NaF. Total bone lesion number was captured for all scans. Bone lesion CT characteristics were grouped into 4 categories (0 = normal, 1 = osteolytic, 2 = osteoblastic and 3 = mixed). Semi-quantitative parameters were divided to create two equally sized groups (low vs high) and the association of imaging parameters and survival was determined with Kaplan-Meier curves. Results: We analyzed 40 pts with non-prostate mGU cancers and osseous metastases with or without additional visceral metastasis. Thirty-four (85%) were males; median age was 56 (range 23-81); Histologically, 19 (48%) had urothelial carcinoma, 8 renal carcinoma, 5 testicular, 2 penile cancer, 2 renal medullary, 2 urachal/adenocarcinoma, 1 mucinous and 1 bladder clear cell. Eighteen pts had mixed bone lesion CT characteristic, 8 osteolytic, 4 osteoblastic and 10 normal. A total of 111 osseous lesions were detected on FDG PET/CT while 251 lesions were detected on NaF PET/CT. FDG PET/CT low vs high SUVmax and low vs high TLG were associated with improved OS [25 months(mo) (95% CI: 14.0 – not estimable) vs 8.8 mo (2.9-25.4), p = 0.034], and [25.4mo (17.0 – not estimable) vs 8.8 mo (2.9 -24.9), p = 0.018], respectively. There was no difference in OS for pts with bone only disease compared to pts with bone and visceral disease [21mo (8.4-37.2 vs 14 mo (3.2-25.4), p = 0.12] though there was a difference in PFS [13.4mo (4.8-18.3) vs 4.5 mo (1.7-5.8), p = 0.044]. There were no NaF PET/CT semi-quantitative parameters that were associated with survival outcomes, and CT characterization of osseous lesions was also not found to be associated with survival outcomes. Conclusions: FDG PET/CT semi-quantitative parameters showed potential prognostic capabilities in pts with non-prostate mGU malignancies with bone +/- visceral metastases treated on a phase I study with CaboNivo +/- Ipi. Additional parameters and histologic subsets will be presented.

Interdisciplinary management of a patient with medication-related osteonecrosis of the jaw: A clinical report

Medication-related osteonecrosis of the jaw (MRONJ) can be induced by Bisphosphonates (BRONJ), Denosumab, and other antiresorptive or antiangiogenic medications. The number of affected patients with MRONJ is increasing worldwide including in Japan. The treatment often includes surgical resection of necrotic bone and the resulting oral defect impairs oral functions which requires consultation with a maxillofacial prosthodontist before and after surgery for prosthetic rehabilitation. Therefore, there is an urgent need to improve collaboration among different institutions for better patient care. In this report, we emphasize the benefits of such collaboration during the treatment of a female patient with BRONJ in the right maxilla. This patient had breast cancer and received zoledronic acid therapy for the treatment of metastatic osseous lesions. The successful team-based collaboration allowed early restoration of oral functions after surgery using an immediate surgical obturator as well as after delivery of the definitive prosthesis. (Int J Maxillofac Prosthetics 2023;6:16-19)

MP45-17 CORRELATION BETWEEN CTC COUNTS AND RADIOMIC METRICS FROM MULTIPLE OSSEOUS METASTATIC LESIONS IN METASTATIC PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022MP45-17 CORRELATION BETWEEN CTC COUNTS AND RADIOMIC METRICS FROM MULTIPLE OSSEOUS METASTATIC LESIONS IN METASTATIC PROSTATE CANCER Bino Varghese, Steven Cen, Gareth Morrison, Jonathan Buckley, Dejerianne Ostrow, David Quinn, Timothy Triche, Amir Goldkorn, and Vinay Duddalwar Bino VargheseBino Varghese More articles by this author , Steven CenSteven Cen More articles by this author , Gareth MorrisonGareth Morrison More articles by this author , Jonathan BuckleyJonathan Buckley More articles by this author , Dejerianne OstrowDejerianne Ostrow More articles by this author , David QuinnDavid Quinn More articles by this author , Timothy TricheTimothy Triche More articles by this author , Amir GoldkornAmir Goldkorn More articles by this author , and Vinay DuddalwarVinay Duddalwar More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002611.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Identify CT radiomic correlates for liquid biopsy metrics such as circulating tumor cells (CTC) counts in patients with metastatic prostate cancer (PC). Together, CT radiomics and liquid biopsy could detect clonal heterogeneity and aid in improved patient management. METHODS: Under IRB-approved informed consent, blood was collected from 22 patients with metastatic castrate resistant PC (mCRPC). CTC counts were enumerated using CellSearch platforms. Five osseous metastatic lesions were manually segmented from CT scans in the same patients using ITK-SNAP by an experienced radiologist. Cancer imaging phenomics toolkit (CaPTk) was used for radiomics analysis. A panel of 6 metrics representing first-order statistical measures: Intensity and second-order statistical measures: Greylevel cooccurrence matrix (GLCM) were calculated from each segmented lesion per patient. Mixed model correlation was used to examine correlation between weighted average of radiomic features from the five bone lesions per patient and their CTC counts. Benjamini-Hochberg Procedure was used to control false discovery rate from multiple comparisons. RESULTS: The distribution of CTC counts was 102±198 (min: 0, max: 692). Among the 69 texture features extracted from the bone lesions, the weighted average of Intensity-based inter-quartile-range and GLCM-based kurtosis, variance and standard-deviation extracted from the 5 bone lesions per patient showed statistically significant correlation with CellSearch enumerated CTC counts ranged between 0.71 to 0.79 with adjusted p-value < 0.01). Radiomics and liquid biopsy have theoretically comparable advantages: they are both noninvasive, can be quantified and followed serially to evaluate disease progression. While their exact role in clinical practice is yet to be established, we conducted a preliminary integrative assessment of the two, within a small cohort. We show that the weighted average of select radiomic metrics extracted from multiple bone lesions (N=5) provide strong correlates for CTC counts. CONCLUSIONS: Post validation in larger cohorts, radiomic corelates of liquid biopsy parameters such as CTC counts may provide surrogates for assessment of the likelihood of recurrence and metastasis in PC. With the widespread applicability of artificial intelligence in healthcare, diverse information about tumor behavior based on its genotype and phenotype decoded via imaging, may predict treatment failures earlier than with conventional methods. Source of Funding: NCI: 1R01CA257610-01 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e769 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bino Varghese More articles by this author Steven Cen More articles by this author Gareth Morrison More articles by this author Jonathan Buckley More articles by this author Dejerianne Ostrow More articles by this author David Quinn More articles by this author Timothy Triche More articles by this author Amir Goldkorn More articles by this author Vinay Duddalwar More articles by this author Expand All Advertisement PDF DownloadLoading ...

Accuracy of 68Ga-PSMA PET/CT for lymph node and bone primary staging in prostate cancer.

The aim of this study is to assess the accuracy of the 68Ga-PSMA PET/CT for lymph nodes and bones in the primary stage of prostate cancer. A total of 126 patients who were submitted to 68Ga-PSMA PET/CT from January 2016 to February 2019 for prostate cancer staging, detection of clinically significant lesions or active surveillance were included in this study. All studies were read by 2 experienced physicians (a nuclear physician and a radiologist). The reports were made in consensus and used by one of the authors to classify the exam in positive or negative. We evaluated presence of abnormal uptake in the prostate, lymph nodes, and bone. The reference standards were histopathological confirmation, confirmatory imaging exams and/or clinical follow-up showing lesion(s) regression after specific treatment, or typical osseous metastatic lesions and highly increased PSA levels. Measurement of diagnostic performance indicated a sensitivity, specificity and accuracy of 75%, 96.3%, and 90.8%, respectively, for lymph node involvement, and 90.9%, 50%, and 76.5%, respectively for metastatic bone lesions. This study showed high specificity and accuracy of 68Ga-PSMA PET/CT for lymph node and bone involvement in prostate cancer staging.

Common Skeletal Neoplasms and Nonneoplastic Lesions at 18F-FDG PET/CT.

Numerous primary and metastatic osseous lesions and incidental osseous findings are encountered at fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT. These lesions show varying degrees of FDG uptake. Malignancies are generally more FDG avid than are benign lesions, but many exceptions exist. Although aggressive lesions tend to be more FDG avid than nonaggressive lesions, this concept holds true particularly for lesions of the same histologic subtype. In addition, some benign osseous processes such as Paget disease have variable degrees of FDG avidity on the basis of disease metabolic activity. This creates a diagnostic dilemma for radiologists and clinicians, especially in patients with known malignancies, and can result in unnecessary diagnostic imaging or interventions for incidental osseous lesions. Evaluation of morphologic CT characteristics of osseous lesions at FDG PET/CT can be a valuable adjunct to metabolic analysis to further characterize lesions, enhance diagnostic and staging accuracy, and avoid unnecessary invasive biopsy procedures. The authors review the common primary and metastatic bone lesions at FDG PET/CT, with an emphasis on morphologic CT assessment of lesions to help narrow the differential diagnosis. Imaging manifestations of common incidental nonneoplastic bone lesions at FDG PET/CT are discussed to provide information on differentiation of these lesions from osseous neoplasms. The guidelines of the National Comprehensive Cancer Network (NCCN) for common primary osseous malignancies are also summarized. Online supplemental material is available for this article. ©RSNA, 2021.

Case series of diffuse extraneural metastasis in H3F3A mutant high-grade gliomas: Clinical, molecular phenotype and literature review

H3K27M and H3.3G34R/V mutations have been identified in pediatric high-grade gliomas (pHGG), though extraneural metastases are rarely reported and poorly characterized. Three pHGG patients from two institutions were identified with extraneural metastasis, harboring histone mutations. Their clinical, imaging and molecular characteristics are reported here. A 17-year old female presented with supratentorial H3.3G34R-mutant glioma with metastatic osseous lesions in the spine, pelvis, bone marrow, pleural effusion and soft tissue of pelvis. Bone marrow biopsy and soft tissue of pelvis biopsy showed neoplastic cells positive for P53. A 20-year old female was diagnosed with H3F3A H3K27M–mutant thalamic glioma. She developed diffuse sclerotic osseous lesions. Biopsy of an osseous lesion was non-diagnostic. A 17-year old female presented with a H3F3A H3K27M-mutant diffuse midline glioma with diffuse spinal cord metastasis. She further developed multifocal chest lymphadenopathy, pleural effusions, and a soft tissue mass in the abdominal wall. The latter was positive for H3K27M mutation. We present the first case series of pHGG with H3F3A mutation and diffuse extraneural dissemination, describing their clinical and molecular profile.

Denosumab Induced Severe Prolonged Hypocalcemia in Metastatic Prostate Cancer

Background: Denosumab is a RANK-l inhibitor that, in addition to the treatment of osteoporosis, is used in patients with advanced cancer and metastatic bone disease to prevent skeletal-related events. Although denosumab is generally safe and effective, it can cause hypocalcemia which in some patients can be severe and life threatening. We present a case of severe prolonged hypocalcemia after a single dose of denosumab in a patient with metastatic prostate cancer. Case: A 78-year-old male with a past medical history of stage 4 prostate cancer on antiandrogen treatment with GnRH antagonist presented with severe hypocalcemia. Physical exam revealed a blood pressure 125/80 mm Hg, pulse 115 per min and weight 135 lb with negative Chvostek’s and Trousseau’s signs. The electrocardiogram showed supraventricular tachycardia with prolonged QTc interval of 503 ms (<430 ms). Labs showed serum calcium 4.9mg/dL (8.5–10.5), albumin 2.5g/dL (3.6–5.1), corrected calcium 5.7 mg/dL, ionized serum calcium 0.64mmol/L (1.05–1.3), creatinine 1.10mg/dL (0.7–1.2), eGFR >60, phosphorus 2.0mg/dL (2.5–4.5), magnesium 1.9 mg/dL (1.6–2.6), 25-OH vitamin D 29.7 ng/mL (30–100), 1,25 dihydroxy vitamin D 174 pg/mL (18–64), iPTH 244.0 pg/mL (11–68) and PSA 1860 ng/mL. Three weeks prior to presentation, the patient received 120 mg of subcutaneous denosumab. Pre-treatment serum calcium was 9.2 mg/dL (8.5–10.5), and Tc-99m bone scan showed multiple osteoblastic osseous metastatic lesions involving both axial and appendicular skeleton. The patient was diagnosed with denosumab-induced severe hypocalcemia and started on intravenous (IV) calcium gluconate infusion, oral phosphate 250 mg twice daily, and ergocalciferol 50,000 IU twice weekly. He required IV calcium gluconate up to 10 g per day in addition to oral calcium carbonate 2 g t.i.d. for 2 weeks to resolve hypocalcemia and normalize QTc interval. Patient was discharged to nursing home on calcium carbonate 2 g q.i.d. with IV calcium gluconate as needed to keep corrected calcium >8.0 mg/dL. After discharge he required up to 4 g of IV calcium and 8 g of oral calcium per day. Unfortunately, he presented again with severe hypocalcemia 5 weeks after discharge. In addition to current regimen of oral and IV calcium boluses, low dose calcitriol was started. We were only able to maintain his serum calcium>8.0 mg/dL by administering high daily dose of oral calcium carbonate 8 g /day and calcitriol 2 mcg daily. Due to poor prognosis, he was transitioned to hospice care and died 2 weeks later. Discussion: There are not many case reports on severe prolonged hypocalcemia secondary to denosumab in cancer patients but normal kidney function. Our patient remained on high dose of calcium even 101 days after denosumab administration. Reference: 1. Milat F et al. Prolonged hypocalcemia following denosumab therapy in metastatic hormone refractory prostate cancer. Bone. 2013 Aug 1;55(2):305–8.

Accuracy and diagnostic value of diffusion-weighted whole body imaging with background body signal suppression (DWIBS) in metastatic breast cancer

BackgroundBreast cancer is the most common malignant tumor among women. The mortality of the patients could be mainly attributed to metastasis and spread of breast cancer to distant sites. The objective of the current study is to evaluate and express the role of diffusion-weighted whole body imaging with background body signal suppression (DWIBS) in detection of osseous and soft tissue metastatic lesions in patients with cancer breast.ResultsThe current prospective study included 50 female patients with pathologically proven breast cancer. The overall sensitivity of DWIBS and STIR were 97.5% and 92.5%, respectively. DWIBS was the most sensitive sequence with highest negative predictive values. DWIBS and STIR were the most sensitive with the highest negative predictive value. Both DWIBS and STIR detected more vertebral metastatic deposits (100% and 97.8%, respectively) and more soft tissue lesions (94.4% for both) than WB DWI and T1WI.ConclusionDWIBS MRI sequence is an effective method for detection of solid organ, bone and lymph node metastasis but not specific for characterization of lesions.

Risks and Complications After Arthroplasty for Pathological or Impending Pathological Fracture of the Hip

BackgroundTreatment options for metastatic osseous lesions of the proximal femur include hemiarthroplasty (HA) or total hip arthroplasty (THA) depending on lesion characteristics and patient demographics. Studies assessing short-term outcomes after HA/THA in this patient population are limited. Therefore, the purpose of this present study was to identify short-term rates of morbidity and mortality after HA/THA for pathological proximal femur fractures, as well as readmission and reoperation rates and reasons. MethodsThis study utilized a large, prospectively collected registry to identify patients who underwent HA/THA between 2011 and 2018. Patients were stratified by indication for surgery, including pathological fracture, nonpathological fracture, and osteoarthritis. Baseline patient characteristics and postoperative complications were compared using bivariate and/or multivariate analysis. ResultsIn total, 883 patients undergoing HA/THA for a pathological fracture were identified. Relative to an osteoarthritis cohort, these patients tended to be older, had a lower body mass index, and had significantly more preoperative comorbidities. These patients had high rates of total complications (13.93%), including thirty-day mortality (3.29%), unplanned return to the operating room (4.98%), and pulmonary complications (3.85%). Patients with pathological fracture had a longer operative duration relative to osteoarthritis and nonpathological cohorts (+27 and +25 minutes, respectively), despite having high rates of HAs performed. ConclusionPatients undergoing hip arthroplasty for pathologic proximal femur fracture have increased morbidity and mortality relative to an osteoarthritis cohort. However, patients with a pathological fracture have similar rates of morbidity and mortality when compared with a nonpathological fracture cohort, but did experience higher rates of perioperative blood transfusion and unplanned readmissions. Level of EvidenceIII.

Multimodality imaging of greater trochanter lesions.

PurposeGreater trochanter (GT) lesions are relatively uncommon. They can be traumatic, infective including tuber-culosis, inflammatory, and neoplastic (primary and metastatic osseous lesions). Although imaging of greater trochanter lesions remains essential for differential diagnoses, an image-guided biopsy is a mainstay for diagnosis and to guide subsequent management.Material and methodsA retrospective search for the word ‘greater trochanter’ was performed of a computerised radiology information system (CRIS) of a tertiary referral centre for orthopaedic oncology over a period of 12 years (2007-2019). This revealed 6019 reports with 101 neoplasms. The imaging, histology, and demography were reviewed by a dedicated musculoskeletal radiologist.ResultsWe identified 101 GT neoplasms with a mean age of 51.5 years (range 6 to 85 years) and a slight female predominance of 1.2 : 1 (46 males and 55 females). Using 30 years of age as a cut-off, we further segregated the patient cohort into 2 groups: 26 (25.74%) lesions in patients less than 30 years age and the remaining 75 (74.26%) lesions in patients over 30 years old. Chondroblastoma was the most common neoplasm in patients below 30 years of age, and metastases were the most common neoplasms in patients over 30 years of age.ConclusionsGreater trochanter pathologies show a broad spectrum of aetiologies. Imaging including radiographs, computed tomography, magnetic resonance imaging, and nuclear medicine scans help to narrow down the differen-tials diagnosis.

Feasibility of Controlling Metastatic Osseous Pain Using Three Kinds of Image-Guided Procedures for Thermal Microwave Ablation: A Retrospective Study.

ObjectivesTo evaluate the feasibility and safety of treating painful osseous metastases using image‐guided percutaneous thermal microwave ablation.MethodsThis is a retrospective study of patients treated from December 2016 to December 2019 in one institute. A total of 50 patients (35 men, 15 women; mean age 55.24 ± 11.03 years) with 56 osseous metastatic lesions underwent image‐guided percutaneous microwave ablation. There were 7 patients with multiple and 43 patients with single metastases. The numbers of patients with primary cancer were as follows: lung, 13; liver, 17; kidney, 10; prostate, 1; breast, 3; osteosarcoma, 1; and thyroid, 5. Seventeen patients had cancer combined with soft tissue masses. The radiological images for the ablative procedures were obtained by CT, fluoroscopy with ultrasound, and fluoroscopy alone in 16, 11, and 23 patients, respectively. Pain severity was estimated using the visual analogue scale before and after treatment (1 week, 1 month, and 3 months after treatment). Radiological evaluations were performed at baseline and 3 months after the procedure.ResultsIn all patients, pain reduction occurred from the first day after treatment. Pain did not recur during the 3 months of follow up. The mean total ablation time per microwave electrode was 3.99 ± 2.48 min (range, 1–15 min). The mean power of the microwave electrode was 66.40 ± 12.08 W. The average volume of bone (load‐bearing bone, such as vertebra and acetabulum) cement after ablation was 2.82 ± 0.81 mL. There were no significant differences in visual analogue scale pain scores for different imaging techniques or ablation energies. No procedure‐related complications occurred.ConclusionImage‐guided percutaneous thermal microwave ablation of osseous metastases relieves pain and improves mobility. CT remains the first choice for percutaneous ablation. Fluoroscopy combined with ultrasound is effective for cases with soft tissue masses; fluoroscopy is also suitable for combination with vertebroplasty. However, further investigations are required.

Combined 18F-naf and fluciclovine administration for PET imaging of prostate cancer.

e17533 Background: 18F-fluciclovine is FDA approved for the detection of recurrent and metastatic prostate cancer. At our institution, 18F-fluciclovine PET had replaced 18F-NaF PET, but fluciclovine has mild to no uptake in dense sclerotic bony lesions. F18-NaF offers increased sensitivity and specificity in detection of osseous metastases and therefore we converted to using a combination of 18F-NaF and 18F-fluciclovine in patients with biochemical recurrence. In this study, we assessed the feasibility of performing a combined F18- fluciclovine and F18-NaF study, and evaluated the biodistribution of the combined radiotracers in patients with prostate cancer. Methods: We retrospectively reviewed 16 consecutive patients over a period of 3 months. 5 mCi of F18-NaF was injected, followed 45 minutes later by a 10 mCi injection of F18-fluciclovine. Patients were asked to hydrate after NaF injection and empty their bladder immediately prior to scanning. A non-diagnostic CT for attenuation correction and an emission PET scan were acquired on a time of flight Discovery 690 PET/CT (GE Healthcare) within 5 minutes of fluciclovine injection. We characterized the extent of soft tissue and osseous disease, as well as assessed the image quality, taking note for F18-NaF excretion in the bladder and the potential scatter artifact limiting evaluation of the prostate bed. Results: On average patients received 5.5 +/- 0.5 mCi of F18-NaF and 10.4 +/- 0.8 mCi of F18-fluciclovine. All 16 patients had diagnostic quality scans. None had limited evaluation of the prostate bed secondary to artifacts from bladder scatter. 10 patients (62.5%) had residual or recurrent prostate cancer within the prostate bed, of which 3 (18.8%) had distant nodal disease in the perirectal, pelvis, retroperitoneal, or periaortic lymph node regions. 7 patients (43.8%) demonstrated osseous metastatic lesions within the clavicle, sternum, iliac wing, vertebra, coccyx, or sacrum. Conclusions: Combined 18F-NaF and 18F-fluciclovine scans in patients with prostate cancer is a feasible method for detecting soft tissue recurrence and osseous disease. Bladder excretion from F18-NaF does not obscure the prostate bed nor degrades the diagnostic quality of the exam. The combined use of 18F-fluciclovine and F18-NaF in one PET/CT acquisition has the potential to increase the sensitivity for detecting prostate cancer and limit the time and radiation dose delivered compared to the conventional, separate acquisitions of the two radiotracers.

Alpha-Particle Therapy for Multifocal Osteosarcoma: A Hypothesis.

Osteosarcoma (OST) is the most common bone tumor in children and adolescents with a second peak of incidence in elderly adults usually diagnosed as secondary tumors in Paget's disease or irradiated bone. Subjects with metastatic disease or whose disease relapses after the initial therapy have a poor prognosis. Moreover, multifocal OST contains tumor-initiating cells that are resistant to chemotherapy. The use of aggressive therapies in an attempt to eradicate these cells can have long-term negative consequences in these vulnerable patient populations. 227Th-labeled molecular probes based on ligands to OST-associated receptors such as IGF-1R (insulin-like growth factor receptor 1), HER2 (human epidermal growth factor receptor 2), and PSMA (prostate-specific membrane antigen) are expected to detect and treat osseous and nonosseous sites of multifocal OST. Published reports indicate that 227Th has limited myelotoxicity, can be stably chelated to its carriers and, as it decays at targeted sites, 227Th produces 223Ra that is subsequently incorporated into the areas of increased osteoblastic activity, that is, osseous metastatic lesions. Linear energy transfer of α particles emitted by 227Th and its daughter 223Ra is within the range of the optimum relative biological effectiveness. The radiotoxicity of α particles is virtually independent of the phase in the cell cycle, oxygenation, and the dose rate. For these reasons, even resistant OST cells remain susceptible to killing by high-energy α particles, which can also kill adjacent quiescent OST cells or cells with low expression of targeted receptors. Systemic side effects are minimized by the limited range of these intense radiations. Quantitative single-photon emission computed tomography of 227Th and 223Ra is feasible. Additionally, the availability of radionuclide pairs, for example, 89Zr for positron emission tomography and 227Th for therapy, establish a strong basis for the theranostic use of 227Th in the individualized treatment of multifocal OST.