Evaluation Of Bone Lesions Research Articles

Role of MRI Zero Echo Time in the Evaluation of Bone Lesions

Role of MRI Zero Echo Time in the Evaluation of Bone Lesions

AO-176, a Differentiated Clinical-Stage Anti-CD47 Antibody, Demonstrates Potent Anti-Tumor Activity across Multiple Preclinical Models of B Cell Neoplasms

Upregulation of CD47, the “don't eat me” signal, on the surface of tumors to evade immune surveillance is a common escape mechanism utilized during hematological malignancy and solid tumor development, progression, and relapse. We recently reported that AO-176, a clinical stage humanized anti-CD47 IgG2 antibody, possesses differentiated characteristics such as preferential binding of tumor cells compared to normal cells, negligible binding to red blood cells, non-ADCC direct tumor killing and elicits immunogenic cell death and DAMP induction, all in addition to single-agent phagocytosis. In vivo, AO-176 has exhibited broad anti-tumor activity in preclinical xenograft models of multiple myeloma (MM), acute myeloid leukemia, T cell acute lymphoblastic leukemia, and Burkitt lymphoma. In this study, the anti-tumor activity of AO-176 in an expanded set of preclinical models of B cell neoplasms was evaluated. We assessed In vivo anti-tumor activity in a diffuse large B cell lymphoma (DLBCL) preclinical xenograft model by inoculating Toledo cells into NSG mice and treating once weekly with either 25 mg/kg AO-176 or human IgG2 isotype control. Treatment with AO-176 resulted in profound tumor shrinkage, achieved complete responses in 8/10 mice, and extended survival for all treated mice through the 46 day dosing period, compared to all isotype control treated tumors reaching endpoint by day 21.Having previously observed significant tumor shrinkage and extension of survival in subcutaneous xenograft models of MM, we sought to evaluate anti-tumor activity of AO-176 in an orthotopic model of MM. Luciferase expressing RPMI-8226 cells were inoculated via intratibial injection into NOD-SCID mice and treated with either 25 mg/kg of AO-176 or human IgG2 isotype control once weekly. AO-176-treated mice showed significant reductions of bioluminescence on study days 7, 21, 35, and 41, and serum paraprotein at study end. Evaluation of bone lesions by x-ray showed significantly reduced average bone lysis score in the AO-176 treatment group at study day 41. We then compared the anti-tumor activity of AO-176 against the second generation proteosome inhibitor carfilzomib in a myeloma xenograft model. AO-176 dosed at 25 mg/kg once weekly achieved 72% TGI, compared to 47% and 27% TGI for tumors treated with 5 mg/kg and 2.5 mg/kg carfilzomib at day 29 post treatment.To elucidate the pathways and processes that may be underpinning the anti-tumor activity of AO-176, we performed bulk RNA sequencing on AO-176 or isotype control-treated tumors harvested at multiple time points from a MM xenograft model we previously reported as exhibiting profound sensitivity to AO-176 in vivo. Murine transcripts from harvested tumor RNA were evaluated to assess differences in immune infiltrate resulting from AO-176 treatment. Days 3 and 7 post treatment with AO-176 showed the greatest number of differentially expressed genes compared to control treated tumors. The top enriched pathway on day 3 was microglia phagocytosis. Principal component analysis of gene expression indicated partitioning of day 3 post AO-176 treatment from the rest of the groups. Furthermore, deconvolution of abundances of infiltrating immune cells using CIBERSORT via TIMER analytical tool showed an enrichment of macrophages relative to other cell types on day 3 post treatment.To extend our RNA sequencing findings, we then sought to evaluate intratumoral immune cell populations after AO-176 treatment in a subcutaneous MM xenograft model. MM cells were inoculated into NOD-SCID mice, then treated with 25 mg/kg AO-176 or human IgG2 isotype control. At 48 hours post treatment, tumors were harvested, and we observed an increase of macrophages in the AO-176 treated tumors, confirming our previous results.In summary, the robust preclinical data in DLBCL and MM warrants further development of AO-176 for treatment of hematological malignancies. AO-176 is being evaluated in phase 1/2 clinical trials for the treatment of patients with solid tumors (NCT03834948) and with MM (NCT04445701). DisclosuresWilson: Arch Oncology: Current Employment. Richards: Arch Oncology: Current Employment. Andrejeva: Arch Oncology: Current Employment. Capoccia: Arch Oncology: Current Employment. Puro: Arch Oncology: Current Employment. Donio: Arch Oncology: Current Employment. Hiebsch: Arch Oncology: Current Employment. Kashyap: Arch Oncology: Current Employment. Pereira: Arch Oncology: Current Employment.

Cognitive map to support the diagnosis of solitary bone tumors in pediatric patients.

ObjectiveTo present a cognitive map to support the radiological diagnosis of solitary bone tumors, as well as to facilitate the determination of the nature of the tumor (benign or malignant), in pediatric patients.Materials and MethodsWe selected 28 primary lesions in pediatric patients, and we identified the findings typically associated with each of the diagnoses. The method used for the construction of the final cognitive map was the Bayesian belief network model with backward chaining.ResultsWe developed a logical, sequential structure, in the form of a cognitive map, based on the Bayesian belief network model, with the intention of simulating the sequence of human thinking, in order to minimize the number of unnecessary interventions and iatrogenic complications arising from the incorrect evaluation of bone lesions.ConclusionWith this map, it will be possible to develop an application that will provide support to physicians and residents, as well as contributing to training in this area and consequently to a reduction in diagnostic errors in patients with bone lesions.

DESCRIPCIÓN Y EVALUACIÓN ANATÓMICA DE LESIONES ÓSEAS CRÁNEO-MANDIBULARES EN CETÁCEOS ODONTOCETOS DEL MAR PERUANO

A total of 308 skulls and 200 jaws from 20 species and one hybrid of odontocetes cetaceans from the Peruvian Ocean were revised for anatomical description and evaluation of bone lesions. They were grouped into 8 types, plus those at the dental alveoli and osteolitic lesions caused by the nematode Crassicauda sp. From the total bone samples, at least 31.2% showed one type of craneo-mandibular lesion whereas the bottle nosed dolphin (Tursiops truncatus) was the most affected. Dental alveoli lesions were found in 13.3% of the samples and bone lesions caused by Crassicauda sp. were in 17.3% of the skulls. The most frequent lesions were hyperostosis and osteolisis, followed by osteomyelitis, malformations and occipitoatlantoaxial ankylosed joints. Adult males showed higher frequency of bone and dental alveolar lesions and is suggested that the latter type of lesions could be associated with severe cases of osteomyelitis and osteolisis at the maxilar and mandibular level. The pterigoid bone was the most affected by the Crassicauda sp. nematode.

Clinical implication of PET/CT and skeletal bone survey in evaluation of multiple myeloma and related monoclonal disorders.

e18574 Background: Whole body skeletal x-ray is considered a gold standard for detecting bone lesions in patients with plasma cell disorders. PET/CT has been increasingly used but its role is yet to be defined. We conducted this study to compare the role of these two imaging modalities in evaluation of plasma cell disorders. Methods: This is single institution, retrospective study to evaluate the role of skeletal survey and PET/CT in patients with multiple myeloma, smoldering myeloma and MGUS. Patients’ records, imaging reports and subsequent management plan were reviewed and compared. Results: A total of 16 patients were reviewed. Among them, 11 patients had multiple myeloma, 2 had smoldering myeloma, and 3 had MGUS. 7/11 patients with multiple myeloma had concordant findings on skeletal survey and PET. 3 of these patients had negative skeletal surveys but had positive finding on PET/CT. PET/CT also identified plasmacytomas in 2 patients. In 2 patients with smoldering myeloma, both skeletal survey and PET/CT were negative. 2/3 patients with MGUS had lytic lesions on skeletal surveys which were not revealed by subsequent PET/CT’s. Both patients were observed without treatment and at 2 years follow up did not show disease progression. Conclusions: Our retrospective analysis showed that skeletal survey is still important for base-line evaluation of bone lesions in multiple myeloma and related monoclonal disorders. PET/CT is more sensitive for detection of bone lesions and can also detect extraosseous lesions such as plasmacytomas. Using tumor metabolic activity, PET/CT may improve diagnostic accuracy and is complementary to conventional skeletal survey. [Table: see text]

Pulmonary Adenocarcinoma Associated with SAPHO Syndrome Difficult to Differentiate from Multiple Bone Metastasis

The patient was a 57-year-old man with a chief complaint of anterior chest pain who was diagnosed with clinical stage IV (c-T2N2M1) non-small-cell lung cancer (adenocarcinoma). Tenderness in the sternoclavicular joint, acne, periodontitis, and palmoplantar pustulosis were evident, and SAPHO syndrome was diagnosed. SAPHO syndrome is a rare disorder that results in synovitis, acne, pustulosis, hyperostosis, and osteomyelitis. Bone scintigraphy showed tracer accumulation in the costal cartilage, sternoclavicular joint, and cervical vertebrae 6-7. Although the bone lesions of SAPHO syndrome were difficult to differentiate from bone metastasis of pulmonary adenocarcinoma, metastatic bone tumors were ruled out by magnetic resonance imaging, computed tomography, and fluorodeoxyglucose positron emission tomography. There have been no previously reported cases of lung cancer with comorbid SAPHO syndrome. We report such a case and discuss the relevant literature, particularly that concerned with the evaluation of bone lesions.

Imaging exams of bone lesions in patients with diffuse cutaneous leishmaniasis (DCL)

We studied bone lesion alterations in three patients with diffuse cutaneous leishmaniasis (DCL) by imaging exams (radiography and scintigraphy) and histopathology. Two patients had bone lesions of distal extremities of hands and feet, and one infiltrating plaques in the skin. The study was conducted at three specialized centers (Presidente Dutra Hospital/Nucleus of Tropical Pathology, UFMA-MA; Gonçalo Moniz Research Center-FIOCRUZ-BA; Laboratory of Pathology of Infectious Diseases (LIM-50), University of São Paulo, SP). Three-phase bone scintigraphy demonstrated high sensitivity and specificity for bone lesions, showing increased uptake of the radiopharmaceutical at sites of active lesions. In contrast, radiography demonstrated lytic lesions, cortical destruction and local osteopenia of the bone extremeties in two patients. Histopathological analysis showed sequestration with presence of amastigote forms of Leishmania (osteomyelitis), mononuclear cells and macrophages containing amastigote forms of Leishmania in one patient. These preliminary data indicate that imaging exams (radiography and scintigraphy) are important in the evaluation of bone lesions in diffuse cutaneous leishmaniasis and should be included in the routine histopathological diagnosis of the disease and follow-up of bone lesions.

Bone remodelation markers are useful in the management of monoclonal gammopathies

The evaluation of bone disease in multiple myeloma (MM) by conventional radiology has low reproducibility. In the last decade, several serum and urine biochemical parameters, for evaluation of bone turnover, have become available. The present study was designed to explore the value of six bone remodelation markers. It was studied in a series of 176 newly diagnosed patients with monoclonal gammopathies (107 MM and 69 monoclonal gammopathies of unknown significance (MGUS)). As control groups we used 25 patients with benign osteoporosis (BO) and 32 healthy individuals (HI). The bone markers analyzed included: bone resorption markers (BRM) (total pyridinoline, total deoxypyridinoline, free deoxypyridinoline and C-terminal telopeptide of collagen I) and bone formation markers (BFM) (bone alkaline phosphatase (bAP) and osteocalcin (OC)). Serum or urinary levels of BRM were significantly higher in MM patients than in MGUS patients, BO patients or HI (P < 0.001, respectively). BRM were higher in MM patients with lytic lesions. However, only C-terminal telopeptide discriminated MM patients without bone lesions from MGUS patients. BFM did not show significant differences in the aforementioned comparisons, although a trend toward higher values of OC and lower values of bAP in patients with early bone affectation was observed. Ratios BRM/BFM that contained bAP exhibited differences that were most significant between the MM group and other entities, as well as between the different MM subgroups. In fact, the ratios BRM/bAP provided discrimination between the MM subgroup without lyses and MGUS group (P < 0.01). BRM and BFM, especially the ratios, are useful in the evaluation of bone lesions in patients with monoclonal gammopathies.

Core needle biopsy for bone tumours

Introduction: Percutaneous core biopsy of bone lesions provides early and definitive diagnosis and guides decisions on management. It is an inexpensive examination technique and has negligible complication rates. Methods: We performed a prospective study of 136 patients who underwent core biopsies for bone lesions over an 18-month period. A Jamshidi (J) needle was used to obtain a core of tissue and specimens were sent for histopathological examination. Biopsy results were analysed for adequacy, ability to yield diagnostic information and for accuracy of diagnosis. Results: The mean age of patients was 27.5 years with a range of 3–72 years. There were 84 males and 52 females in the study. Histopathological diagnosis was obtained in 121 (89%) patients. The specimen was non-diagnostic in 15 patients. Fourteen patients required two attempts and two patients required three attempts at biopsy. Sixty-two of 64 patients (96.9%) who had a confirmed final diagnosis had an accurate J-needle histopathological diagnosis. None of the patients had any major complications. Discussion: Core needle biopsy is an important tool in the evaluation of bone lesions. It is a safe, reliable and accurate procedure and yields diagnostic information in a high proportion of patients. It has several advantages over an open bone biopsy.

The use of rare-earth radionuclides and other bone-seekers in the evaluation of bone lesions in patients with multiple myeloma or solitary plasmacytoma.

Twenty-four patients with multiple myeloma and 4 with solitary plasmacytoma had total-body scans after intravenous injection of 67Ga-citrate alone (17 patients) or combined with other agents (11 patients). The latter included 99mTc-diphosphonate (99mTc-DP), 99mTc-polyphosphate (99mTc-PP), or 99mTc-sulfur colloid (99mTc-SC) given alone or combined with 171Er, 157Dy, or 167Tm as citrate. In some patients more than one agent was compared to 67Ga and radiographic bone surveys. In general, localization of the rare-earth "bone-seekers" was poor except for 157Dy, which compared well with 99mTc-PP and 99mTc-DP; 157Dy was also helpful in studies of the abdomen and pelvis because of its failure to concentrate in the gastrointestinal tract. No toxic or nonspecific effects were noted.