Bone Lesions Research Articles

Abstract CT222: Efficacy and safety of ceralasertib in the PLANETTE study in patients (pts) with ATM-altered advanced solid tumors (ASTs) or metastatic castration-resistant prostate cancer (mCRPC)

Abstract Background: Ceralasertib, a potent, selective ATR inhibitor, is synthetically lethal in ATM-deficient preclinical models. This Phase 2a study (NCT04564027) assessed ceralasertib monotherapy in previously treated pts with ATM-altered tumors. Methods: Adult pts had ASTs excluding NSCLC (Cohort [Co] A; data cutoff [DCO] Dec 21 2022) or mCRPC (Co B; DCO Apr 28 2023) and germline/somatic ATM pathogenic/likely pathogenic variants (PVs) by local assessment. ATM alterations were centrally confirmed by FMI F1CDx in tumor and/or FMI F1 liquid CDx in circulating tumor DNA, and/or by ATM protein deficiency by immunohistochemistry (cutoff ≤5%). Primary endpoints were objective response rate (ORR) in Co A and composite response rate (CRR) in Co B. Safety was a secondary endpoint. Results: The initial starting dose of 240 mg BID PO ceralasertib on Days 1-14 of a 28-day cycle was reduced to 160 mg BID due to hematologic toxicity. Results are reported for 30 pts in Co A and 15 pts in Co B with a starting dose of 160 mg BID. In Co A, the 28 pts with centrally confirmed ATM alterations (93.3% [28/30] with ATM PV and 36.7% [11/30] ATM-deficient) had an ORR of 7.1% (80% CI: 1.9, 17.9): 1 complete response in breast cancer (ongoing at 12 mos) and 1 partial response in endometrial cancer (ongoing at 9 mos), both ATM-deficient. In Co B, the 13 pts with centrally confirmed ATM alterations (73.3% [11/15] with ATM PV and 46.7% [7/15] ATM-deficient) had a CRR of 7.7% (80% CI: 0.8, 26.8): 1 pt with conversion of circulating tumor cell count from unfavorable to favorable (ongoing at 3 mos) with unknown ATM expression. The safety profile was manageable (Table). Steady-state ceralasertib plasma concentrations exceeded the IC90 for ~23 hrs/day. Conclusion: Responses to ceralasertib monotherapy were limited in ATM-altered tumors, despite reaching target plasma levels. Alternative pt selection and combination treatment strategies are being explored. TABLE 1: NAND Efficacy, safety of ceralasertib 160 mg BID on D1-14 of D28 cycle in pts with ATM-altered ASTs/mCRPC Cohort A: ASTs Cohort B: mCRPC Efficacy Response rate in pts with centrally confirmed ATM alterations, % (80% CI)* N=28 7.1 (1.9, 17.9)† N=13 7.7 (0.8, 26.8)‡ Response rate in pts with centrally confirmed ATM PVs, % (80% CI) N=28 7.1 (1.9, 17.9) N=11 9.1 (1.0, 31.0) Response rate in pts with centrally confirmed ATM-deficiency, % (80% CI) N=11 18.2 (4.9, 41.5) N=7 0.0 (0.0, 28.0) Safety, n (%) N=30 N=15 TEAEs 30 (100) 15 (100) Grade ≥3 TEAEs 15 (50.0) 8 (53.3) TRAEs 21 (70.0) 13 (86.7) Grade ≥3 TRAEs 6 (20.0) 5 (33.3) Serious TEAEs 4 (13.3) 4 (26.7) Serious TRAEs 2 (6.7) 1 (6.7) TEAEs leading to discontinuation 1 (3.3)§ 0 TEAEs leading to death 0 0 TEAEs (any grade) occurring in ≥20% of pts in either cohort, n (%) N=30 N=15 Nausea 13 (43.3) 8 (53.3) Abdominal pain 9 (30.0) 1 (6.7) Anemia 8 (26.7) 7 (46.7) Fatigue 8 (26.7) 5 (33.3) Asthenia 8 (26.7) 2 (13.3) Decreased appetite 7 (23.3) 3 (20.0) *Centrally confirmed ATM-altered patients were patients with either ATM PV confirmed by FMI F1CDx in tumor and/or by FMI F1 liquid CDx in circulating tumor DNA and/or ATM protein-deficient by immunohistochemistry assay at Ventana with cut-off ≤5%. Thus, ATM PV patients could also have ATM protein-deficiency. †Objective response by RECIST v1.1, in centrally confirmed ATM-altered patients. ‡Composite response: by RECIST v1.1 for soft tissue and visceral lesions and PCWG3 criteria for bone lesions; confirmed conversion of circulating tumor cell count from ≥5/7.5 mL blood to <5/7.5 mL; or confirmed prostate-specific antigen decline of >50%, in centrally confirmed ATM-altered patients. §Discontinuation due to decreased appetite classified as a serious adverse event. ASTs, advanced solid tumors; CI, confidence interval; mCRPC, metastatic castration-resistant prostate cancer; PV, pathogenic variant; pts, patients; TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event Citation Format: Rahul Aggarwal, Antoine Italiano, Susan Domchek, Oscar Goodman, Sophie Postel-Vinay, Jesus Garcia-Donas, Tanya Dorff, Zachery Reichert, Philippe Cassier, Neal Shore, Catherine Marshall, Graeme Parr, Itziar Irurzun-Arana, Neel Shah, Natalia Lukashchuk, Olga Murina, Daniel Slade, Bienvenu Loembé, Emma Dean, Elhan Sanai, Wassim Abida. Efficacy and safety of ceralasertib in the PLANETTE study in patients (pts) with ATM-altered advanced solid tumors (ASTs) or metastatic castration-resistant prostate cancer (mCRPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT222.

Abstract CT075: A Phase 1 trial evaluating AC699, an orally bioavailable chimeric estrogen receptor degrader, in patients with advanced or metastatic breast cancer

Abstract Background The role of estrogen receptor (ER) signaling in driving breast carcinogenesis is well established, and endocrine therapy has been a mainstay in the treatment of patients with ER-positive advanced or metastatic breast cancer for decades. Aromatase inhibitors, selective estrogen receptor modulators, and selective ER degraders (SERDs) such as fulvestrant, and more recently elacestrant, are integral components of the therapeutic strategy for patients with ER-positive breast cancer. However, unmet medical need persists in this patient population, due to suboptimal clinical outcomes and the development of resistance to therapy. E3 ligase-engaged chimeric degraders represent a technological advance with the potential to induce potent and deeper ER degradation. Utilizing Accutar's proprietary Protein-Protein Interaction Targeting Chimeras (PPI-TAC) platform, AC699 was designed as a novel chimeric degrader targeting ERα. By effectively linking an ER ligand to an E3-ligase recruiting ligand, AC699 brings ERα in proximity to an E3 ligase, resulting in ubiquitination and subsequent degradation of ERα. Chimeric ER degraders possess the unique advantage of degrading the ER protein without the inherent risk of activating an ER signal. Moreover, these molecules are not degraded alongside the target protein, allowing for their efficient recycling within the cell. This direct mechanism enables chimeric ER degraders to achieve potent ER degradation with increased specificity, thereby potentially providing a higher therapeutic index compared to SERDs. Study Description The AC699-001 trial is a first in human Phase 1 dose escalation study (NCT05654532) which will enroll up to 60 patients with locally advanced or metastatic ER-positive, human epidermal growth factor receptor 2-negative, breast cancer. Patients must have received at least two prior lines of endocrine treatment, or at least one prior line, if combined with a CDK4/6 inhibitor. Prior chemotherapy is not required but must not exceed three prior lines of cytotoxic treatment. Patients must have at least one measurable lesion or at least one predominantly lytic bone lesion. AC699 is administered orally, once daily, with doses ranging from 100 mg to 600 mg in a standard 3+3 dose escalation design. The primary objective is evaluation of the safety and tolerability of AC699. Secondary objectives include assessment of preliminary anti-tumor activity and characterization of the pharmacokinetic profile of single and multiple doses of AC699. Enrollment began in December 2022 and a total of 5 sites have been activated in the United States. Citation Format: Rachel M. Layman, Manish R. Patel, David Cosgrove, Michael Danso, Nancy Mota, Marjorie E. Zettler, Katherine C. Pehlivan, Erika Hamilton. A Phase 1 trial evaluating AC699, an orally bioavailable chimeric estrogen receptor degrader, in patients with advanced or metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT075.

Detection of Adenocarcinoma of the Colon on 18 F-Fluciclovine PET/CT.

An 85-year-old man with prostate cancer and de novo bone metastases was treated with hormonal therapy with resolution of bone lesions, improved primary disease, and improved serum tumor markers. Although on hormonal therapy, biochemical recurrence prompted performance of 18 F-fluciclovine PET/CT. Fluciclovine PET/CT revealed primary prostate cancer progression with incidental note of avid foci in the colon for which colonoscopy was recommended. Colonoscopy with biopsy was performed with pathology revealing primary colon adenocarcinoma. Before reinitiation of prostate cancer therapy, segmental colon resection was performed with pathology positive for additional sites of colon cancer.

Perceptions regarding the use of a three-dimensionally-printed manufactured educational simulator for periodontal treatment of intraosseous and interradicular lesions.

Treating intraosseous lesions (IOLs) and interradicular bone lesions (IRLs) is an extremely technical dental procedure in periodontics. Instrumentation of these lesions is often perceived as difficult by students and inexperienced dentists before they perform a certain number of procedures on patients in the clinic. The aim of this article is to evaluate a cost-effective three-dimensional (3D)-printed educational simulator for the periodontal treatment of IOLs/IRLs (including scaling, incisions and sutures). The simulators were first developed digitally, and then manufactured using printable resins and specific materials; finally, they were assembled using different bonding systems. To evaluate the simulators, assessments were gathered from two target populations: undergraduate students and periodontics experts. These individuals tested the simulator and completed a cross-sectional questionnaire based on a Likert scale with comparative and pedagogical items scored from one to five. The purpose of the questionnaire was to compare our simulator to clinical reality (i.e., operation on human jaws) and to an animal simulator (i.e., simulation of porcine jaws). The results are expressed as the mean and standard deviation and were statistically analyzed with the Wilcoxon signed-rank test. Overall, the results were satisfactory for both groups of testers (4.70 and 4.61 out of five for students and experts, respectively, for global satisfaction). The overall educational relevance of the simulator designed herein highlights the fact that 3D-printed educational simulators could enable efficient cognitive-functional learning for clinical IOL/IRL treatment.

Weakly-Supervised Detection of Bone Lesions in CT.

The skeletal region is one of the common sites of metastatic spread of cancer in the breast and prostate. CT is routinely used to measure the size of lesions in the bones. However, they can be difficult to spot due to the wide variations in their sizes, shapes, and appearances. Precise localization of such lesions would enable reliable tracking of interval changes (growth, shrinkage, or unchanged status). To that end, an automated technique to detect bone lesions is highly desirable. In this pilot work, we developed a pipeline to detect bone lesions (lytic, blastic, and mixed) in CT volumes via a proxy segmentation task. First, we used the bone lesions that were prospectively marked by radiologists in a few 2D slices of CT volumes and converted them into weak 3D segmentation masks. Then, we trained a 3D full-resolution nnUNet model using these weak 3D annotations to segment the lesions and thereby detected them. Our automated method detected bone lesions in CT with a precision of 96.7% and recall of 47.3% despite the use of incomplete and partial training data. To the best of our knowledge, we are the first to attempt the direct detection of bone lesions in CT via a proxy segmentation task.

Heterogeneity and high prevalence of bone manifestations, and bone mineral density in congenital generalized lipodystrophy subtypes 1 and 2.

Congenital Generalized Lipodystrophy (CGL) is a rare autosomal recessive disease caused by mutations in genes responsible for the formation and development of adipocytes. Bone abnormalities are described. However, there is a scarcity of data. To describe bone characteristics in a large CGL1 and 2 case series. Cross-sectional study that assessed bone radiological features of CGL patients of a reference hospital in Fortaleza (CE), Brazil. Patients underwent clinical and bone mineral metabolism evaluation, radiographs of the axial and appendicular skeleton and bone mineral density (BMD) assessment by DEXA (dual energy X-ray absorptiometry). Nineteen patients were included, fourteen were CGL1 and 5, CGL2. Median age was 20 years (8-42) and 58% were women. Median BMI and percentage of body fat were, respectively, 21 Kg/m² (16-24), and 10.5% (7.6-15). The median leptin concentration was 1 ng/mL (0.1-3.3). Diabetes mellitus and dyslipidemia were present in 79% and 63% of patients, respectively. Median calcium and phosphate were normal in almost all patients (95%). Median parathyroid hormone and 25-OH-vitamin D were 23 pg/mL (7-75) and 28 ng/mL (18-43). Osteolytic lesions, osteosclerosis and pseudo-osteopoikylosis, were present in 74%, 42% and 32% of patients, respectively. Lytic lesions were found predominantly in the extremities of long bones, bilaterally and symmetrically, spine was spared. Osteosclerosis was present in axial and appendicular skeleton. Pseudo-osteopoikilosis was found symmetrically in epiphyses of femur and humerus, in addition to the pelvis. BMD Z-score greater than +2.5 SD was observed in 13 patients (68.4%). BMD was higher in CGL1 compared to CGL2 in lumbar spine and total body in adults. No associations were found between high BMD and HOMA-IR (p=0.686), DM (p=0.750), osteosclerosis (p=0.127) or pseudo-osteopoikilosis (p=0.342), and, between pain and bone lesions. Fractures were found in 3 patients. Bone manifestations are prevalent, heterogeneous, and silent in CGL1 and CGL2. Osteolytic lesions are the most common, followed by osteosclerosis and pseudo-osteopoikilosis. Bone mass is high in most cases. There was no pain complaint related to bone lesions. Thus, systematic assessment of bone manifestations in CGL is essential. Studies are needed to better understand its pathogenesis and clinical consequences.

Contrast-enhanced Susceptibility Weighted Imaging (CE-SWI) for the Characterization of Musculoskeletal Oncologic Pathology: A Pictorial Essay on the Initial Five-year Experience at a Cancer Institution

Susceptibility-weighted imaging (SWI) is based on a 3D high-spatial-resolution, velocity-corrected gradient-echo MRI sequence that uses magnitude and filtered-phase information to create images. It SWI uses tissue magnetic susceptibility differences to generate signal contrast that may arise from paramagnetic (hemosiderin), diamagnetic (minerals and calcifications) and ferromagnetic (metal) molecules. Distinguishing between calcification and blood products is possible through the filtered phase images, helping to visualize osteoblastic and osteolytic bone metastases or demonstrating calcifications and osteoid production in liposarcoma and osteosarcoma. When acquired in combination with the injection of an exogenous contrast agent, contrast-enhanced SWI (CE-SWI) can simultaneously detect the T2* susceptibility effect, T2 signal difference, contrast-induced T1 shortening, and out-of-phase fat and water chemical shift effect. Bone and soft tissue lesion SWI features have been described, including giant cell tumors in bone and synovial sarcomas in soft tissues. We expand on the appearance of benign soft-tissue lesions such as hemangioma, neurofibroma, pigmented villonodular synovitis, abscess, and hematoma. Most myxoid sarcomas demonstrate absent or just low-grade intra-tumoral hemorrhage at the baseline. CE-SWI shows superior differentiation between mature fibrotic T2* dark components and active enhancing T1 shortening components in desmoid fibromatosis. SWI has gained popularity in oncologic MSK imaging because of its sensitivity for displaying hemorrhage in soft tissue lesions, thereby helping to differentiate benign versus malignant soft tissue tumors. The ability to show the viable, enhancing portions of a soft tissue sarcoma separately from hemorrhagic/necrotic components also suggests its utility as a biomarker of tumor treatment response. It is essential to understand and appreciate the differences between spontaneous hemorrhage patterns in high-grade sarcomas and those occurring in the therapy-induced necrosis process in responding tumors. Ring-like hemosiderin SWI pattern is observed in successfully treated sarcomas. CE-SWI also demonstrates early promising results in separating the T2* blooming of healthy iron-loaded bone marrow from the T1-shortened enhancement in bone marrow that is displaced by the tumor. SWI and CE-SWI in MSK oncology learning objectives: SWI and CE-SWI can be used to identify calcifications on MRI. Certain SWI and CE-SWI patterns can correlate with tumor histologic type. CE-SWI can discriminate mature from immature components of desmoid tumors. CE-SWI patterns can help to assess treatment response in soft tissue sarcomas. Understanding CE-SWI patterns in post-surgical changes can also be useful in discriminating between residual and recurrent tumors with overlapping imaging features.

Case Report on Brown Tumor: An Unusual Expression of Renal Osteodystrophy and Secondary Hyperparathyroidism

The new term of ‘Chronic Kidney Disease- Mineral and Bone Disorders’ has been introduced to encompass a wide-ranging syndrome, capturing various abnormalities in bone and mineral metabolism seen in patients with chronic kidney disease. Multifactorial disorders affecting mineral metabolism and bone structure emerge early in the progression of Chronic Kidney Disease. Brown tumors, an uncommon type of bone lesion are distinctive manifestations of high-turnover bone disease. In this case, a patient with chronic kidney disease (dialysis dependent) with IgA nephropathy that presented with multiple osseous lesions of bilateral ribs, sternum, scapula, clavicle, mandible and vertebral bodies. The case highlights the significance of considering brown tumors in the differential diagnosis and management of patients with both an osseous mass and chronic kidney disease. Failing to establish an accurate diagnosis may result in unnecessary additional diagnostic procedures and extensive surgery, ultimately increasing patient morbidity. Through this case report, the importance of preventing, early diagnosing, and treating secondary hyperparathyroidism to reduce the prevalence of high-turnover bone disease and associated complications such as brown tumors is emphasized.

Correlation between CRAB Symptoms and Antioxidant Enzyme Activity in Patients with Multiple Myeloma

To investigate the relationship between clinical indicators of CRAB symptoms and antioxidant enzyme activity in patients with multiple myeloma (MM). The activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in the bone marrow supernatants of 44 patients with MM and 12 patients with non-malignant hematological diseases was detected by colorimetric assay, and then the differences in the activity of antioxidant enzymes between the two groups were compared. Furthermore, the relationship between the activity of antioxidant enzymes in the MM group and the levels of serum calcium, serum creatinine (Scr), hemoglobin (Hb), alkaline phosphatase (ALP) as well as bone lesions were analyzed. The antioxidant enzyme activity was lower in MM patients compared with the control group (P < 0.05). When the concentrations of serum calcium and ALP were higher than the normal levels, Hb was lower than 85 g/L, and there were multiple bone lesions, the activity of CAT, SOD and GPX was significantly declined (P < 0.05); When the concentration of Scr≥177 μmol/L, the activity of GPX was significantly declined (P < 0.05). Regression analyses showed that CAT, SOD and GPX were negatively correlated with serum calcium (r =-0.538, r =-0.456, r =-0.431), Scr (r =-0.342, r =-0.384, r =-0.463), and ALP (r =-0.551, r =-0.572, r =-0.482). The activity of antioxidant enzymes, including CAT, SOD and GPX, were decreased in patients with MM and they were negatively correlated with some clinical indicators of CRAB symptoms (such as serum calcium, Scr, and ALP), which suggests that promoting the activity of antioxidant enzymes may be beneficial to treat the CRAB symptoms of the patients with MM.

Comparison of Ga-68 PSMA PET/CT and Multiparametric MRI for Initial Detection and Staging of Prostate Cancer

Abstract Background Multiparametric magnetic resonance imaging (mpMRI) is widely used for the evaluation of prostate cancer and is known to have better accuracy. Gallium-68 prostate-specific membrane antigen (Ga-68 PSMA) is a radiotracer that shows high localization in prostate cancer cells. Purpose The purpose of this study was to assess the sensitivity and utility of Ga-68 PSMA positron emission tomography/computed tomography (PET/CT) in comparison with mpMRI as a noninvasive imaging technique for the initial diagnosis and locoregional staging of prostate cancer using transrectal ultrasound (TRUS)-guided biopsy as gold standard. Materials and Methods This prospective observational study conducted from August 2017 to April 2020 evaluated 60 men (n = 60) with biopsy-proven prostate carcinoma. They underwent mpMRI and Ga-68 PSMA PET/CT scans within 14 days with TRUS biopsy being gold standard. T staging of disease, N staging of lymph nodes within the pelvis, and M staging of lesions in pelvic bones (within the imaging field of mpMRI) were compared using PSPP version 1.0.1 statistical software. Results All 60 men with a mean age of 69.9 ± 9.35 years showed Ga-68 PSMA avid disease, whereas 55 were detected by mpMRI. The sensitivity in detection of prostate lesions (with 95% confidence interval) was 99.08% for Ga-68 PSMA PET/CT and 84.40% for mpMRI. Ga-68 PSMA PET/CT detected greater number of patients with regional lymph nodal involvement (19/60) as compared with mpMRI (12/60). Ga-68 PSMA PET/CT showed PSMA avid pelvic skeletal lesions in nine patients, whereas mpMRI detected pelvic lesions in six patients. In addition, four other patients showed extrapelvic skeletal lesions on Ga-68 PSMA PET/CT. Conclusion Ga-68 PSMA PET/CT has superior sensitivity in detection of primary prostate tumor, as compared with mpMRI. Both modalities correlate well in detection of seminal vesicle involvement. Ga-68 PSMA PET/CT outperformed mpMRI in detection of lymph nodal and skeletal metastases. Hence, Ga-68 PSMA PET/CT should be considered as first-line diagnostic modality for carcinoma prostate. Summary Statement: Ga-68 PSMA PET/CT shows superior diagnostic performance than mpMRI in the evaluation of prostate cancer.

Can 18F-FES PET Improve the Evaluation of 18F-FDG PET in Patients With Metastatic Invasive Lobular Carcinoma?

Invasive lobular carcinoma (ILC) exhibits a low affinity for 18F-FDG. The estrogen receptor (ER) is commonly expressed in ILCs, suggesting a potential benefit of targeting with the ER probe 18F-FES in this patient population. The objective of this study was to evaluate the diagnostic performance of 18F-FES imaging in patients with metastatic ILC and compare it with that of 18F-FDG. We conducted a retrospective analysis of 20 ILC patients who underwent concurrent 18F-FES and 18F-FDG PET/CT examinations in our center. 18F-FES and 18F-FDG imaging were analyzed to determine the total count of tracer-avid lesions in nonbone sites and their corresponding organ systems, assess the extent of anatomical regions involved in bone metastases, and measure the SUVmax values for both tracers. Among 20 ILC patients, 65 nonbone lesions were found to be distributed in 13 patients, and 16 patients were diagnosed with bone metastasis, which was distributed in 54 skeletal anatomical regions. The detection rate of 18F-FDG in nonbone lesions was higher than that of 18F-FES (57 vs 37, P < 0.001). 18F-FES demonstrated a superior ability to detect nonbone lesions in 4 patients, whereas 18F-FDG was superior in 5 patients (P > 0.05). Among 9/16 patients with bone metastasis, 18F-FES demonstrated a significant advantage in the detection of bone lesions compared with 18F-FDG (P = 0.05). Furthermore, patients with only 18F-FES-positive lesions (12/12) were administered endocrine regimens, whereas patients lacking 18F-FES uptake (2/3) predominantly received chemotherapy. 18F-FES is more effective than 18F-FDG in detecting bone metastasis in ILC, but it does not demonstrate a significant advantage in nonbone lesions. Additionally, the results of examination with 18F-FES have the potential to guide patient treatment plans.

A Lytic Bone Lesion in a 23-month-old Boy from Kenya.

A Lytic Bone Lesion in a 23-month-old Boy from Kenya.

Gorham–Stout disease started with recurrent bilateral exudative pleuritis: case description and literature review

Gorham–Stout disease is an extremely rare skeletal disorder of unknown etiology manifested by multiple foci of osteolysis (“vanishing bone disease”) and lymphangiomatosis. Osteolysis can occur in any part of the skeleton (skull, facial skeleton, ribs, clavicula, spine, pelvic bones, bones of the upper and lower extremities). Approximately half of the patients develop pleural effusion, accompanied by respiratory abnormalities. We describe a case of Gorham-Stout disease with recurrent bilateral exudative pleuritis as a first and most prominent sign, while the bone lesions at the vertebral bodies, ribs and sternum proceeded without active complaints and were an accidental finding during chest computer tomography. Timely diagnosis of the disease depends on the awareness of doctors of various specialties and careful reading of imaging results.

An Uncommon Presentation of Chronic Myeloid Leukemia: Osteolytic Bone Lesion as the Initial Manifestation

An Uncommon Presentation of Chronic Myeloid Leukemia: Osteolytic Bone Lesion as the Initial Manifestation

Multiple Myeloma

The second most common hematologic malignancy is the clonal proliferation of neoplastic plasma cells within the bone marrow. There is the presence of monoclonal immunoglobulins in the serum and/or urine. This results in anemia, myelosuppression, bone destruction, and clinical consequences of para-proteinemia on kidney function and other organ systems. The disease manifests through the acronym CRAB (hypercalcemia, renal impairment, anemia, and bone lesions). Less frequent manifestations of multiple myeloma are of extramedullary localizations. Myeloma cells can become independent of the bone marrow microenvironment, circulate freely in the blood, and infiltrate organs. This results in a high-risk state characterized by increased proliferation, evasion of apoptosis, and treatment resistance. It can affect any area of tissue. Most commonly it involves the pleura, lymph nodes, chest wall, liver, skin/soft tissue, lungs, CNS, genitourinary system, breast and pancreas. In patients with confirmed multiple myeloma, the diagnosis of extramedullary involvement is typically established by the presence of pathological soft tissue masses using radiological methods such as computed tomography (CT) scan, positron emission tomography/CT (PET/CT), magnetic resonance imaging (MRI), or ultrasound, along with biopsy or physical examination. The molecular mechanisms underlying the development of extramedullary multiple myeloma (EMM) have not been fully defined. Various cytogenetic abnormalities are observed, and some studies have generated genomic sequencing profiles that distinguish EMM from classic multiple myeloma. While plasma cell leukemia (PCL) and central nervous system (CNS) EMM indicate a poor prognosis, outcomes for other manifestations can be highly heterogeneous. Sensitive imaging modalities including PET/CT and MRI (Fig.1) are integral components of diagnosis and response assessment. Patients with extramedullary multiple myeloma (EMM) have a clear survival disadvantage.

Ultrasound as a Tool for Initial Diagnosis of Bone Lesions in Children Has Good Predictive Values: A Prospective Study From a University Hospital.

Pediatric bone injuries are traditionally diagnosed using radiography. However, ultrasonography is emerging as an alternative due to its speed and minimal invasiveness. This study assessed the diagnostic capabilities of ultrasound before radiography in a group of 186 children with suspected long bone fractures at Saint Etienne University Hospital (Saint-Priest-en-Jarez, France). Patients with open trauma and severe deformity were excluded. Ultrasonography demonstrated 88.2% sensitivity and 86.4% specificity, with better results for forearm injuries. Of the 186 cases, 162 were consistent with radiography and 24 varied. Factors influencing an accurate diagnosis included the presence of indirect signs, operator experience, and examination duration, while indirect signs often led to misinterpretation. Although ultrasound cannot completely replace radiography due to its limitations in identifying deeper fractures, this study revealed its substantial efficacy and ease, supporting its potential utility in pediatric trauma emergencies.

Effect of a microencapsulated phyto/phycogenic blend supplementation on growth performance, processing parameters, meat quality, and sensory profile in male broilers.

Powered by consumer taste, value, and preferences, natural products including phytogenics and algae are increasingly and separately used in the food systems where they have been reported to improve growth performance in poultry and livestock. The present study aimed to determine the effects of a new feed additive, microencapsulated NUQO© NEX, which contains a combination of phytogenic and phycogenic, on broiler growth performance, blood chemistry, bone health, meat quality and sensory profile. Male Cobb500 chicks (n = 1,197) were fed a 3-phase feeding intervals; 1-14d starter, 15-28d grower, and 29-40d finisher. The dietary treatments included a corn-soy basal Control (CON), basal diet supplemented with NUQO© NEX at 100 g/ton from 1 to 28d then 75 g/ton from d 28 to 40 (NEX75), and basal diet supplemented with NUQO© NEX at 100 g/ton from 1 to 40d (NEX100). The NEX100 supplemented birds had 62 g more BWG increase and 2.1-point improvement in FCR compared with CON in the finisher and overall growth phase (p < 0.05), respectively. Day 40 processing body weights and carcass weights were heavier for the NEX100 supplemented birds (p < 0.05). The incidences of muscle myopathies were also higher in NEX treatments, which could be associated with the heavier weights, but the differences were not detected to be significant. The NEX75 breast filets had more yellowness than other dietary treatments (p = 0.003) and the NEX 100 treatment reduced the levels of breast filet TBARS at 7 days-post harvest (p = 0.053). Finally, both NEX treatments reduced the incidence of severe bone (tibia and femur) lesions. In conclusion, the supplementation of the phytogenic NUQO© NEX improved finisher performance parameters, whole phase FCR, processing carcass weights, and breast filet yellowness, at varying inclusion levels.

Repeatability of 18F-FDG uptake in metastatic bone lesions of breast cancer patients and implications for accrual to clinical trials

BackgroundStandard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases.MethodsFor this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified by the most commonly used PET parameter, the maximum tumor voxel normalized by dose and body weight (SUVmax) and also by the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals for SUVmax and SULpeak were used to determine the limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment.ResultsThe mean relative difference of SUVmax and SULpeak in 38 bone tumors of the first cohort were 4.3% and 6.7%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and − 16.3% for SUVmax, and 21.2% and − 17.5% for SULpeak. 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification using SULpeak for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria for SULpeak changed the status of 3 patients compared to the standard Positron Emission Tomography Response Criteria in Solid Tumors of ± 30% SULpeak.ConclusionIn evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG SUVmax, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions in these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response.

Giredestrant for Estrogen Receptor-Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study.

To compare giredestrant and physician's choice of endocrine monotherapy (PCET) for estrogen receptor-positive, HER2-negative, advanced breast cancer (BC) in the phase II acelERA BC study (ClinicalTrials.gov identifier: NCT04576455). Post-/pre-/perimenopausal women, or men, age 18 years or older with measurable disease/evaluable bone lesions, whose disease progressed after 1-2 lines of systemic therapy (≤1 targeted, ≤1 chemotherapy regimen, prior fulvestrant allowed) were randomly assigned 1:1 to giredestrant (30 mg oral once daily) or fulvestrant/aromatase inhibitor per local guidelines (+luteinizing hormone-releasing hormone agonist in pre-/perimenopausal women, and men) until disease progression/unacceptable toxicity. Stratification was by visceral versus nonvisceral disease, prior cyclin-dependent kinase 4/6 inhibitor, and prior fulvestrant. The primary end point was investigator-assessed progression-free survival (INV-PFS). At clinical cutoff (February 18, 2022; median follow-up: 7.9 months; N = 303), the INV-PFS hazard ratio (HR) was 0.81 (95% CI, 0.60 to 1.10; P = .1757). In the prespecified secondary end point analysis of INV-PFS by ESR1 mutation (m) status in circulating tumor DNA-evaluable patients (n = 232), the HR in patients with a detectable ESR1m (n = 90) was 0.60 (95% CI, 0.35 to 1.03) versus 0.88 (95% CI, 0.54 to 1.42) in patients with no ESR1m detected (n = 142). Related grade 3-4 adverse events (AEs), serious AEs, and discontinuations due to AEs were balanced across arms. Although the acelERA BC study did not reach statistical significance for its primary INV-PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1-mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies.

Quantitative analysis of standardized uptake values (SUV) of metastatic bone lesions in scintigraphy with [99mTc]Tc-EDDA/HYNIC-Tyr3-octreotide in patients with neuroendocrine tumours.

Neuroendocrine tumours (NETs) are a group of cancers that can produce hormones and other metabolically active compounds. The majority of NETs have specific tissue characteristics, such as the expression of somatostatin receptors (SSTR). Metabolic testing with [99mTc]Tc-EDDA/HYNIC-Tyr3-octreotide ([99mTc]Tc-EDDA/HYNIC-TOC) can be used in patients with NETs to visualize the presence of receptors in different locations of pathological lesions, including the skeletal system. The study aimed to calculate the body weight maximum standardized uptake value (SUVbwmax) of pathological bone lesions and healthy bone tissues, estimate the size of lesions, and identify a relationship between the SUVbwmax of the bone tissues, age and body mass of the study participants. The somatostatin receptor scintigraphies (SRS) with [99mTc]Tc-EDDA/HYNIC-TOC were carried out at the Department of Nuclear Medicine, University Clinical Hospital No. 1, Pomeranian Medical University (PMU) in Szczecin from 2019 to 2022. Whole body and single photon emission computed tomography/computed tomography (SPECT/CT) scans were performed four hours after the injection of 700-800 MBq of [99mTc]Tc-EDDA/HYNIC-TOC in 344 patients with neuroendocrine tumours of various primary lesion locations. In 19 patients, who showed foci of increased radiopharmaceutical accumulation in bone location, the SUVbwmax was measured. The SUVbwmax of pathological bone lesions and healthy tissues were determined on SPECT/CT cross-sectional images using Xeleris 4 software. The total number of foci with increased SSTR expression in bone regions seen on scintigraphic images was 89. Among them, 32 bone lesions were visible on the corresponding CT scans. The mean SUVbwmax of these lesions was 31.39 [standard deviation (SD) 34.31]. For the other 57 lesions that were not visible on corresponding CT scans, the mean SUVbwmax was 19.12 (SD 24.24). The smallest bone lesion detected on the scintigram and visible on the corresponding CT location was 5 mm × 5 mm, measured in cross-section, and was located in the Th8 vertebral body; the largest, measuring 20 mm × 22 mm, was detected in the L3 vertebral body. The SUVbwmax of these lesions was 24.70 and 142.40, respectively. Bone lesions seen on SPECT/CT in [99mTc]Tc-EDDA/HYNIC-TOC scintigraphy can be quantitatively analysed using the SUV index. Even a very small pathological bone lesion can be detected on [99mTc]Tc-EDDA/HYNIC-TOC scintigraphy. It was shown that in cases where bone lesions were visible on CT scans, the SUVbwmax of bone tumour lesions was higher than when lesions were not visible on CT. Body mass does not affect the SUVbwmax of bone lesions. SUVbwmax of healthy bone tissue decreased with age.