99mTc Bone Scan Research Articles

Lipoma arborescence of knee joint in an adolescent male patient: a case report

<p>A very uncommon benign synovial membrane tumor is called lipoma arborescens. It often affects a single articulation, the knee. Despite a conventional imaging assessment, the lesion’s histological analysis is still required for the ultimate diagnosis. A 15-year-old boy attended the outpatient clinic of the Lahore General Hospital Lahore, Pakistan with pain and swelling in his left knee that had been steadily worsening over the previous 4 years. There were no concomitant prodromal symptoms, and the swelling was soft and non-tender while also inhibiting knee flexion. Soft tissue shadows were observed on radiographs. A large amount of subarticular erosion in the nearby tibial and femoral condyle was caused by the frond-like proliferation of fatty synovium, according to magnetic resonance imaging. Only the left knee joint showed focused areas of unusually elevated radionuclide uptake during the Technetium (Tc99m) bone scan. After an open synovectomy, the specimen underwent histological analysis, which revealed villiform fatty tissue, a hallmark of Lipoma arborescens coated by somewhat thicker synovium. Although infrequent, open synovectomy is currently the preferred course of treatment for lipoma arborescens, which should be taken into account when making a differential diagnosis of knee diseases. Approximately 3 months after surgery, the patient underwent his most recent follow-up and was asymptomatic with a small amount of joint effusion.</p>

S2212 A Rare Systemic Illness Presenting With Fever and Abdomen Pain

Introduction: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytic disease. ECD can practically involve any organ system in the body with common organs involved being skeletal system, cardiovascular system and the central nervous system. Rarely, other organs like breast, liver, spleen, kidney, testis and thyroid glands were reported to be involved. Case Description/Methods: A 51-year-old female presented to our emergency with fever and left upper quadrant pain abdomen of 10 days. Historically, she was symptomatic for last 3 years with complaints of intermittent fever, knee joints pain, polyuria, nocturia and polydipsia. Contrast enhanced computer tomography (CECT) chest and abdomen showed bilateral pleural and pericardial effusion, thrombosis in splenic vein and right portal vein, splenic infarct, bilateral urothelial thickening with perinephric fat stranding, soft tissue thickening around the aorta and asymmetrical bulky adrenals. PET-CT revealed Flouro-deoxyglucose (FDG) avid ill-defined lesion in the pericardium which was extending into the inter-atrial and atrioventricular septum and FDG avid asymmetrical mural thickening of aorta extending from ascending thoracic aorta up to the infrarenal abdominal aorta. There was presence of bulky tail of pancreas, bulky left adrenal, lytic lesions involving left femoral head, right sacrum and mandible, FDG avid lesions involving meninges, sella and cranial venous sinuses. Tc-99m bone scan showed increased tracer uptake in maxilla, mandible, bilateral forearm bones, bilateral femurs and bilateral tibia. PET guided biopsy from the lytic bone lesion in the right sacrum showed presence of cluster of atypical histiocytes with occasional multinucleated Touton type giant cells. The cells also showed granular cytoplasmic positivity for BRAFV600E, confirming the diagnosis of Erdheim Chester disease (ECD). She was initiated on oral vemurafenib, BRAF inhibitor, at a dose of 240mg twice a day. Discussion: ECD presenting with splenic infarct has not been described previously. A thorough evaluation and targeted biopsy confirmed the diagnosis. BRAFV600E is the most common mutation noted in these patients, seen in nearly 60% of the patients and the patients with BRAF mutations respond well to vemurafenib, a kinase domain inhibitor of mutant BRAF. Here in, we report a patient of ECD who presented with multisite venous thrombosis and splenic infarct, a rare manifestation of ECD, who was treated successfully with vemurafenib.

Necrotising Otitis Externa: An Overview Of Imaging Modalities.

Necrotising Otitis Externa (NOE) has often posed some challenges in view of diagnosis and management by clinicians. One such challenge is the appropriate and timely use of imaging techniques, since its use is critical not only in diagnosis but also determining the extent and resolution of the disease. Hence, doctors in both primary and secondary health care need to be familiar with presenting symptoms, while specialists need to be appraised of advances in imagining techniques in management of NOE. Whilst there is a general consensus amongst clinicians on some aspects of management of NOE, there is very limited consensus on the use of imaging modalities. There is no single modality of imaging that can provide a complete picture of diagnosis, disease progression and resolution. There are some advantages and limitation of each methodology, which indicate that a multi-modal imaging technique at particular stages of the disease may provide better management outcomes. However, further research in this area is required, as there is not yet an established 'gold standard' for imaging in NOE.

Central Skull Base Osteomyelitis: Multimodality Imaging and Clinical Findings from a Large Indian Cohort.

Central or atypical skull base osteomyelitis (CSBO) often presents with severe unrelenting headache and progressive mono or polyneuritis cranialis. MRI and CT are used as initial imaging techniques but have a poor specificity and sensitivity. To analyze our cohort of CSBO. Over a 5-year period [2015-2020], we retrospectively analyzed the records of all patients with CSBO who had undergone a 3T MRI Brain, MR angiography, regional FDG PET-CT, and skeletal scintigraphy with 99mTc MDP/SPECT-CT. Surgical biopsy specimens were sent for bacterial and fungal cultures. In total, 17 patients with CSBO were identified. Typically, 88% of patients presented with severe unilateral headache. All patients had at least a cranial mono or polyneuritis. The majority of patients were diabetic [64%]. MRI was normal in 42% of patients, whereas PET-CT and with 99mTc MDP scan and SPECT-CT were abnormal in all patients. Our series of CSBO showed a 40% mortality rate with significant morbidity and relentless progression. Patients required repeated PET CT and bone scans to detect regression of disease activity. The average duration of IV therapy ranged from 3 weeks to 9 months and oral therapy for around 2-3 months. Cure was defined after taking into account the original diagnosis, symptom resolution, and concordant reduction of tissue uptake on PET CT and 99mTc bone scan. The combination of MRI, FDG PET CT, and 99mTc bone scan with concurrent SPECT CT was able to detect disease and disease progression in all patients.

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.

A Prospective Study Comparing the Role of 18 FDG PET-CT with Contrast-Enhanced Computed Tomography and Tc99m Bone Scan for Staging Locally Advanced Breast Cancer

Locally advanced breast cancer (LABC) patients require an accurate staging of the disease to rule out distant metastases. Various imaging investigations are used to stage LABC patients. The present study is a prospective comparison of conventional imaging (CI) with fusion positron-emission tomography and computed tomography (PET-CT) scans in the staging of LABC patients. Seventy-three consecutive LABC patients presenting to the breast cancer clinic of the tertiary care cancer institute were included in the study. All patients underwent contrast-enhanced computed tomography, Tv99m bone scintigraphy, and fusion PET-CT. Histology of the metastatic site was confirmed wherever possible. The disparity between the two imaging findings was compared. Doubtful lesions were observed clinically for at least 2 years to confirm their nature. PET-CT detected a higher number of lymph nodes in the axilla, internal mammary, and supraclavicular region as compared to CI. PET-CT upstaged 36.98% and downstaged 5.4% of the patients respectively leading to a change in the management in 30.13% of the patients. Sensitivity, specificity, positive predictive value, and negative predictive value of CI and PET-CT were 71.87%, 87.80%, 82.14%, and 80%, and 90.90%, 90%, 88.23%, and 92.30% respectively. PET-CT was more accurate in staging the LABC patients as compared to CI. PET-CT is more accurate then contrast-enhanced CT and bone scintigraphy for staging locally advanced breast carcinoma patients. It can replace multiple organ-directed imaging in staging breast cancer. It can provide accurate staging of the disease so that patients can be prognosticated and can be directed to the most appropriate treatment plans.

Self-inflicted finger cold injury leading to amputation: Report of a case.

A cold injury can result in devastating outcomes, leading to significant morbidity and loss of distal extremities. Amputations are common after severe frostbite injuries with delayed presentation, often mediated by post-injury arterial thrombosis. Ischemic injuries are managed according to the ischemia time. The most controversial aspect of treating a salvage injury is the time of surgical intervention, which used to be based on the previous management dogma freeze in January, amputate in July. Recently, the paradigm has shifted to early surgical management if the level of viability of the deep structure can be ascertained using 99mTc pertechnetate scintigraphy (99mTc bone scans). We present a case of a finger amputation resulting from a cold injury secondary to a crush injury.

A novel artificial intelligence biomarker: Validation of the automated bone scan index (aBSI) in veterans with metastatic prostate cancer.

e17507 Background: Prostate cancer commonly metastasizes to the bone and is associated with reduced survival, pathologic fractures and bone pain. The assessment of bone lesions is made with the technetium Tc99m(99mTc) bone scan, which relies on the subjective interpretation of radiologists and has a wide interobserver variability. There is an unmet need for a more objective and quantifiable measurement tool. Progenics Pharmaceuticals has introduced an automated bone scan index (aBSI), which employs artificial intelligence to quantify skeletal tumor burden. The automated bone scan index has been prospectively validated and is reproducible in large Phase III studies. The aBSI was validated by our study in the Veteran population at the West LA VA Medical Center. Methods: The first positive technetium 99 Tc99m bone scans of veterans diagnosed with metastatic, castration-sensitive prostate cancer were evaluated. Since 2011, a total of 107 evaluable patient bone scans were studied (n = 107). Patients with visceral metastases were excluded to evaluate only those with skeletal metastases. An automated bone scan index (aBSI) was generated for each scan using the Progenics Pharmaceuticals’ artificial intelligence platform. Multivariate analysis of aBSI with overall survival, prostate cancer specific survival, time from diagnosis to first positive bone scan, age at diagnosis, ethnicity, and Gleason score was assessed. Results: The study demonstrated a wide range of aBSI values (Range 0-16.84). Values calculated above the Median aBSI value (1.0) were prognostic for Overall Survival (p = 0.0009) and Prostate Cancer-Specific Survival (p = 0.0011). Patients in the highest quartile of aBSI values (range 5.2-16.84) showed a statistically significant Prostate Cancer-Specific Mortality (p = 0.0300) when compared to the lowest two quartiles (Range 0-1.07). The time from diagnosis to the first positive Tc99m bone scan statistically correlated with aBSI values (p = 0.0016). Multivariate analysis using Cox regression was utilized in the final statistical analysis of prostate cancer-specific mortality and overall survival. Conclusions: The automated Bone Scan Index provides a quantifiable and validated artificial intelligence biomarker to address an unmet need among metastatic prostate cancer patients. This tool was validated among Veterans, a pertinent population that is commonly affected by metastatic prostate cancer.

Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole\u2013body magnetic resonance imaging in radio-recurrent prostate cancer

BackgroundAccurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer.Methods/designThe LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort.DiscussionThe LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway.Trial registrationLOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.

P2725Transthyretin cardiac amyloidosis in heart failure with preserved ejection fraction: Imaging by Tc-99m bone scan

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome with multiple underlying causes. Transthyretin amyloidosis (ATTR) is an underdiagnosed cause of HFpEF. Extraosseous uptake, in particular, myocardial uptake, was observed in a number of ATTR patients examined with the bone scan tracers. Objectives We sought to determine the prevalence of ATTR as detected by the bone scan among the patients admitted due to HFpEF. Methods We screened all consecutive patients ≥60 years old admitted due to HFpEF (left ventricular ejection fraction ≥50%). All eligible patients were offered an echocardiogram and a bone scan (a 99mTc-DPD/MDP/HMDP scintigraphy). Echocardiographic and clinical variables were gathered in all the subjects. The intensity of the myocardial uptake was graded according to a visual scale ranging from 0 to 3 points, in which the absence of uptake was assigned a score of 0 points; uptake less than that of bone (referred to as the adjacent rib), 1 point; uptake similar to that of bone, 2 points; and uptake greater than that of bone, 3 points. The distribution of the uptake in myocardium was defined as focal uptake, diffuse uptake, uptake in a ventricular wall segment, diffuse ventricular uptake, or diffuse biventricular uptake. Results The study included 62 HFpEF patients (52% women, 73±9 years). The bone scintigraphic analysis revealed relatively intense myocardial uptake in 7 of 62 patients (11.2%). 7 patients had intense Tc-99m uptake (score of 2–3) in the cardiac region, showing deposition in both right and left ventricles in every case. Patients with amyloid deposition were older (78±6 vs. 70±12 years, p&lt;0.05), had a lower systolic blood pressure (118±23 vs. 148±28 mmHg, p&lt;0.05), and left ventricular ejection fraction (52±11 vs. 58±6%, p&lt;0.05). Both groups had at least moderate left ventricular hypertrophy and abnormal global longitudinal strain with no significant difference between groups. In 6 all the cases, the final diagnosis of amyloidosis was based on the results of abdominal fat aspiration biopsy. Conclusion ATTR is an underdiagnosed disease that accounts for a significant number (11.2%) of HFpEF cases. These findings create an opportunity for further investigation in the targeted therapy of patients with HFpEF.

Oncological Outcome of Cytoreductive Radical Prostatectomy in Prostate Cancer Patients With Bone Oligometastases

ObjectiveTo explore the role of cytoreductive radical prostatectomy (CRP) for locally resectable and distant oligometastatic prostate cancer (CaP). Patients and MethodsOligometastases were defined as the presence of 5 or fewer metastatic lesions detected on 99mTc bone scan and no suspicious visceral involvement at pretreatment imaging. Clinical data on 111 consecutive patients who were diagnosed as oligometastatic CaP in our center from 2005 to 2016 was retrospectively collected. In this retrospective cohort study, 35 patients underwent CRP and androgen deprivation therapy, and 76 patients underwent androgen deprivation therapy alone. Oncological outcomes were analyzed by employing Kaplan-Meier method. ResultsThe median follow-up of both groups was 35 months. In whole cohort analyses, prostate-specific antigen (PSA) decrease velocity (P = .167), PSA half-time (P = .263), and PSA nadir (P = .196) were not significantly different between 2 groups. Meanwhile, the differences in oncological outcomes between 2 groups did not reach statistical significance with regard to PSA relapse-free survival (P = .184), clinical progression-free survival (P = .118), and cancer-specific survival (P = .773). In addition, similar results were also observed in prespecified subgroup analyses (lower PSA group [0-100 ng/mL, P = .543], lower Gleason score group [6-7, P = .266], lower clinical T stage group [2-3 stage, P = .962], lower radiological N stage group [0 stage, P = .364]). ConclusionIn our study, significant benefit from CRP has not been detected in patients with oligometastatic CaP. Facing current trend, it demands deliberate consideration to select candidates for cytoreductive surgery, and the selection criteria should be further refined by incorporating additional prognostic factors.

A phase II study for prostate cancer monitoring using 18F-DCFPyL and blood-based biomarkers.

TPS3154 Background: Assessing treatment response in castrate resistant prostate cancer (CRPC), remains a challenge due to the limited sensitivity and specificity of existing imaging modalities. Understanding prostate cancer biology with tumor biopsies does not address the issue of tumor heterogeneity or cellular degradation during the decalcification process of bone biopsies. Next generation positron emission tomography (PET) imaging and circulating biomarkers might provide additional insights on treatment responses and inform clinical decision-making earlier in therapy. 18F-DCFPyL (PyL) is a second-generation fluorinated PSMA PET tracer that has superior sensitivity and specificity to detect prostate cancer compared to standard imaging. Its role in assessing tumor response to therapy has not been evaluated. Circulating tumor DNA (ctDNA) in blood can provide tumor genomic information, while exosomes in serum and urine may provide data on the proteomic landscape of tumors. Methods: We are conducting a prospective study of 15 men with metastatic CRPC who are scheduled to start a new systemic therapy for their disease. Upon enrollment, subjects will have baseline assessments with standard cross-sectional imaging, 99mTc bone scan, and blood work. Standard scans will be performed every 8-12 weeks until progression of disease. PyL PET/CT scans and liquid biopsies (ctDNA and exosomes) will occur at baseline, 6 weeks after starting their new therapy, and at disease progression. Lesions seen on PET/CT images will be identified by a certified reader. The maximum standardized uptake value (SUVmax) will be measured and recorded in up to the five hottest lesions and normalized to a background SUVmean measured in the liver, spleen, kidney, mediastinum, and parotid glands. Changes in the normalized SUV from baseline to the 6-week PyL PET scan will be correlated to PSA response by the Pearson’s correlation coefficient. The Kaplan-Meier method will be used to evaluate progression free survival and overall survival dichotomized by the median value of SUV change. Blood for ctDNA and exosomes will be stored for future analysis. The study is open with two patients enrolled at the time of submission. One patient has completed his initial PyL PET/CT scan. Clinical trial information: NCT03585114.

Accessory ossicles of the foot-an imaging conundrum.

Various anatomical variations can be found in the foot and ankle, including sesamoid bones and accessory ossicles. These are usually incidental findings and remain asymptomatic; however, they may cause complications resulting in painful syndromes or degenerative changes secondary to overuse or trauma. They can also lead to fractures or simulate fractures. These complications are challenging to diagnose on radiographs. Advanced imaging with US, CT, MRI, or Tc-99m bone scan is useful for definitive diagnosis. This study aims to illustrate how imaging modalities can be used to diagnose complications of common sesamoids and accessory ossicles of the ankle and foot (hallux sesamoids, os trigonum, accessory navicular, os supranaviculare, os peroneum, os intermetatarseum, and os calcaneus secundarius) and demonstrate the imaging differences between fractures and their mimics.

Phase 3 Assessment of the Automated Bone Scan Index as a Prognostic Imaging Biomarker of Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer

Prostate cancer commonly metastasizes to bone, and bone metastases are associated with pathologic fractures, pain, and reduced survival. Bone disease is routinely visualized using the technetium Tc 99m (99mTc) bone scan; however, the standard interpretation of bone scan data relies on subjective manual assessment of counting metastatic lesion numbers. There is an unmet need for an objective and fully quantitative assessment of bone scan data. To clinically assess in a prospectively defined analysis plan of a clinical trial the automated Bone Scan Index (aBSI) as an independent prognostic determinant of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). This investigation was a prospectively planned analysis of the aBSI in a phase 3 multicenter randomized, double-blind, placebo-controlled clinical trial of tasquinimod (10TASQ10). Men with bone metastatic chemotherapy-naïve CRPC were recruited at 241 sites in 37 countries between March 2011 and August 2015. The statistical analysis plan to clinically evaluate the aBSI was prospectively defined and locked before unmasking of the 10TASQ10 study. The analysis of aBSI was conducted between May 25, 2016, and June 3, 2017. The associations of baseline aBSI with OS, radiographic progression-free survival (rPFS), time to symptomatic progression, and time to opiate use for cancer pain. Of the total 1245 men enrolled, 721 were evaluable for the aBSI. The mean (SD) age (available for 719 men) was 70.6 (8.0) years (age range, 47-90 years). The aBSI population was representative of the total study population based on baseline characteristics. The aBSI (median, 1.07; range, 0-32.60) was significantly associated with OS (hazard ratio [HR], 1.20; 95% CI, 1.14-1.26; P < .001). The median OS by aBSI quartile (lowest to highest) was 34.7, 27.3, 21.7, and 13.3 months, respectively. The discriminative ability of the aBSI (C index, 0.63) in prognosticating OS was significantly higher than that of the manual lesion counting (C index, 0.60) (P = .03). In a multivariable survival model, a higher aBSI remained independently associated with OS (HR, 1.06; 95% CI, 1.01-1.11; P = .03). A higher aBSI was also independently associated with time to symptomatic progression (HR, 1.18; 95% CI, 1.13-1.23; P < .001) and time to opiate use for cancer pain (HR, 1.21; 95% CI, 1.14-1.30; P < .001). To date, this investigation is the largest prospectively analyzed study to validate the aBSI as an independent prognostic imaging biomarker of survival in mCRPC. These data support the prognostic utility of the aBSI as an objective imaging biomarker in the design and eligibility of clinical trials of systemic therapies for patients with mCRPC. ClinicalTrials.gov Identifier: NCT01234311.

Abstract CT129: Phase 2 study of cabozantinib in patients with non-breast, non-prostate cancer with bone metastasis

Abstract IntroductionWe sought to test the safety and efficacy of cabozantinib in patients with advanced solid (non-breast, non-prostate) malignancies and bony metastasis (ClinicalTrials.gov Identifier: NCT01588821). Patients with bone metastasis were enrolled in this study. Primary endpoint of the study was change in bone biomarkers in serum and urine. Tumor responses were an additional endpoint and measured by RECIST v1.1. Methods:Participants with progressive metastatic solid tumors other than breast and prostate cancer, age &amp;gt;/= 18 yrs, and with bone metastasis were consented and enrolled onto open label phase II study at Massachusetts General Hospital. The starting dose was 60 mg/d cabozantinib. CT of the tumor, chest, abdomen, and pelvis were performed every 2 cycles (each cycle = 28 days). Serial PET and Tc99m bone scans were performed in a subset of participants. Radiologic tumor responses were evaluated by RECIST. Bone biomarkers were measured at baseline and week 8, with a bony response to treatment defined as ≥ 40% decrease in urinary Ntx, serum Ntx, or serum Ctx at week 8. Results:37 patients enrolled onto this study. 14 had sarcoma, 7 renal cell carcinoma, 5 non-small cell lung cancer, 4 head and neck carcinoma, 2 thyroid cancer, 2 melanoma, 1 adenoid cystic carcinoma, 1 metastatic chondroblastoma, and 1 chordoma. Patient age at enrollment ranged from 18 to 83 years, with an average age of 54.4 years old. 37 % of patients were female. 19 patients were evaluable for determination of response by bone biomarkers. 13 had ≥ 40% decrease in serum Ctx, 9 had ≥ 40% decrease in serum Ntx, and 8 had ≥ 40% decrease in urinary Ntx. These measurements, however, had low correlation with RECIST measurements (r^2 of .05, .00, and .15, respectively).The average time to disease progression was 6.6 months. 3 patients had a partial response by RECIST (with chondroblastoma, head and neck cancer, and thyroid cancer), 16 of 20 radiologically measureable patients had some decrease in tumor size as best response, and 9 of those 16 had decrease in tumor size by 10% or greater by RECIST, and 6 of those 9 had sarcoma or chondroblastoma. The other 17 of 37 enrolled patients had bone only disease or were otherwise not measureable by RECIST. 55% of patients required dose reduction. Most common all grade adverse events were fatigue (59%), nausea (46%), anorexia (32%), and plantar-palmar erythrodysesthesia (27%). Conclusion:Cabozantinib is an active drug for patients with bone metastasis as measured by changes in serum/urine Ntx and Ctx. Plantar-palmar erythrodysesthesias, fatigue, nausea, and anorexia were common adverse events. Adverse events were manageable by dose reduction to 40 mg QD. This is the first study showing that cabozantinib has significant anti-tumor activity in patients with metastatic sarcoma with bone metastasis. Citation Format: Edwin Choy, Gregory M. Cote, M. Dror Michaelson, Lori Wirth, Justin F. Gainor, Lecia V. Sequist, Ryan J. Sullivan, Panagiotis M. Fidias, Alice Shaw, Rebecca S. Heist. Phase 2 study of cabozantinib in patients with non-breast, non-prostate cancer with bone metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT129. doi:10.1158/1538-7445.AM2017-CT129

Within Normal Limits

wrist: Frontal radiograph of the wrist performed showing interval development of diffuse lucency seen throughout the carpal bones with severe crowding of the carpal joints.FigureFigureFigureA 67-year-old man with a past medical history of complicated diabetes, hypertension, and hyperlipidemia who presented to the hospital after a fall was found to have methicillin-resistant Staphylococcus aureus (MRSA) bacteremia from endocarditis. He developed wrist pain during his hospital stay, and an initial radiograph showed mild degenerative changes of the wrist. He continued to have worsening right wrist pain, swelling, and soft tissue erythema. A follow-up radiograph was performed two weeks after the initial radiograph, and it showed interval development of diffuse lucency throughout the carpal bones with severe crowding of the carpal joints. (Photo.) His physicians were concerned about septic joint and infection, especially because the lucency developed so quickly. MRI of the wrist confirmed septic arthritis-osteomyelitis involving the distal radius, all of the carpal bones, and the proximal second-fifth metacarpals. Osteomyelitis (OM) may occur from hematogenous seeding, contiguous spread from adjacent infected soft tissues, or direct inoculation. Hematogenous OM is usually monomicrobial, but OM from contiguous spread or direct inoculation is usually polymicrobial. Long bones are usually the most affected in children, favoring the metaphysis over epiphysis over joints. (Diagnostic Imaging: Musculoskeletal Non-Traumatic Disease. Philadelphia: Elsevier; 2016.) The most common location in adults is adjacent to any site of ulceration or in the joints themselves. Complications of untreated OM are severe, and can destroy the epiphyses in children and joints in adults and cause septicemia and death. Most OM is caused by bacterial etiologies, and treatment consists of long-term IV antibiotic treatment tailored to the pathogen. (Overview of Osteomyelitis in Adults. UpToDate.com; April 2017.) Surgery may be necessary if there is evidence of abscess, joint infection, or subperiosteal collections. The approach to diagnosing OM starts with a plain radiograph, and changes include cortical destruction adjacent to a site of soft tissue ulceration and abrupt loss of joint space or periosteal reaction. It is important to note that changes in OM may not be seen on plain radiographs for one to two weeks, and repeat radiographs should be performed. MRI is the modality of choice to diagnose OM due to high sensitivity and specificity, and should be employed emergently for clinical suspicion of infection because bone changes on x-ray lag behind the infection by 10-20 days. MRI changes include confluent T1 low signal intensity, fluid sensitive sequences that show increased signal intensity within bone and adjacent soft tissues, and enhancement of the bone in contrast-enhanced T1 sequences. (Diagnostic Imaging: Musculoskeletal Non-Traumatic Disease. Philadelphia: Elsevier; 2016.) Multiphase nuclear medicine Tc-99m bone scan may be considered when MRI is not possible, and it will show increased radiotracer uptake on all phases in acute OM. (Diagnostic Imaging: Musculoskeletal Non-Traumatic Disease. Philadelphia: Elsevier; 2016.) Direct tissue sampling is usually obtained to identify the causes and further direct treatment. Share this article on Twitter and Facebook. Access the links in EMN by reading this on our website or in our free iPad app, both available at www.EM-News.com. Comments? Write to us at [email protected].

WE-FG-202-05: Quantification of Bone Flare On [F-18] NaF PET/CT in Metastatic Prostate Cancer

Purpose: Bone flare has been observed on Tc-99m bone scans during early assessment in metastatic Castration-Resistant Prostate Cancer (mCRPC) patients receiving select androgen-signaling pathway (AR) targeted treatments, including CYP17-inhibitor Abiraterone. This study investigates the appearance and potential clinical impact of bone flare in mCRPC patients receiving CYP17-inhibitors using 18F-NaF PET/CT. Methods: Twenty-three mCRPC patients being treated with CYP17-inhibitors received NaF PET/CT scans at baseline, week 6, and week 12 of treatment. Individual lesions were identified using a SUV>15 threshold within skeletal regions and articulated bone registration was used to track lesions between scans. Standard SUV metrics were extracted globally for each patient (pSUV) and for each individual lesion (iSUV). Differences in metrics across time-points were compared using Wilcoxon signed-rank tests. Cox proportional hazard regression analyses were conducted between global metrics and progression-free survival (PFS). Results: Nineteen patients (83%) showed increasing NaF PET global metrics at week 6, with pSUVtotal reflecting consensus change across other global metrics with median increase +33% (range +2 to 205%). Of these patients, 14 showed subsequent decrease in pSUVtotal, with a median of −17% (range −76 to −1%), indicating flare phenomenon. Increasing pSUVmean at week 6 correlated with extended clinical PFS (HR = 0.58, p=0.02). New lesions did not account for the initial increase in global NaF metrics. Lesion-level analysis reveals 316 lesions in the 14 patients exhibiting global flare. On average, 75% (sd: 22%) of lesions follow global trends with iSUVtotal increasing at week 6 and 65% (sd: 17%) showing iSUVtotal decrease at week 12. Conclusion: Bone flare was detected on NaF PET/CT in the first 6 weeks of treatment for mCRPC patients receiving CYP17-inhibitors, subsiding by week 12. Characterization provided in this study suggests prolonged PFS in patients showing bone flare early in select AR-directed treatments. Prostate Cancer Foundation

ACR Appropriateness Criteria Follow-Up of Malignant or Aggressive Musculoskeletal Tumors

Appropriate imaging modalities for the follow-up of malignant or aggressive musculoskeletal tumors include radiography, MRI, CT, 18F-2-fluoro-2-deoxy-D-glucose PET/CT, 99mTc bone scan, and ultrasound. Clinical scenarios reviewed include evaluation for metastatic disease to the lung in low- and high-risk patients, for osseous metastatic disease in asymptomatic and symptomatic patients, for local recurrence of osseous tumors with and without significant hardware present, and for local recurrence of soft tissue tumors. The timing for follow-up of pulmonary metastasis surveillance is also reviewed.The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Sclerosing Osteomyelitis in the Long Bone

Clinical Presentation: A 26-year-old woman presented with a 5-year history of pain, upper arm swelling, and slight limitation of elbow range of motion. Radiographs indicated marked expansion and sclerosis of the humerus (Figures 1a and 1b). The blood examination findings were normal. 99m-Tc diphosphonate bone scans indicated increased activity in the sclerotic area in the humerus (Figure 1c). A biopsy was performed to confirm the diagnosis. A histopathological examination revealed chronic inflammation, fibrosis, and no malignancy. No growth was noted on bacterial examination. Her parents stated that elbow swelling was present since she was 4 or 5 years old, for which she had received some antibiotics via drip infusion that resolved her symptoms. The treatment of sclerosing osteomyelitis is usually determined on an individual basis. In this case, non-steroidal anti-inflammatory drugs were administered for more than 10 years, and the patient’s condition has not worsened. This disease is also known as Garre’s sclerosing osteomyelitis. Bacterial infection is highly suspected as a cause of this disease, but culture examination is usually negative like this case

Development of a nomogram model predicting current bone scan positivity in patients treated with androgen-deprivation therapy for prostate cancer.

Purpose: To develop a nomogram predictive of current bone scan positivity in patients receiving androgen-deprivation therapy (ADT) for advanced prostate cancer; to augment clinical judgment and highlight patients in need of additional imaging investigations.Materials and methods: A retrospective chart review of bone scan records (conventional 99mTc-scintigraphy) of 1,293 patients who received ADT at the Memorial Sloan-Kettering Cancer Center from 2000 to 2011. Multivariable logistic regression analysis was used to identify variables suitable for inclusion in the nomogram. The probability of current bone scan positivity was determined using these variables and the predictive accuracy of the nomogram was quantified by concordance index.Results: In total, 2,681 bone scan records were analyzed and 636 patients had a positive result. Overall, the median pre-scan prostate-specific antigen (PSA) level was 2.4 ng/ml; median PSA doubling time (PSADT) was 5.8 months. At the time of a positive scan, median PSA level was 8.2 ng/ml; 53% of patients had PSA <10 ng/ml; median PSADT was 4.0 months. Five variables were included in the nomogram: number of previous negative bone scans after initiating ADT, PSA level, Gleason grade sum, and history of radical prostatectomy and radiotherapy. A concordance index value of 0.721 was calculated for the nomogram. This was a retrospective study based on limited data in patients treated in a large cancer center who underwent conventional 99mTc bone scans, which themselves have inherent limitations.Conclusion: This is the first nomogram to predict current bone scan positivity in ADT-treated prostate cancer patients, providing high predictive accuracy.