Osseous Metastases Research Articles

BIOM-04. SINGLE-CELL RNA SEQUENCING PROTOCOL OF THE HUMAN METASTATIC PROSTATE SPINE TUMOR MICROENVIRONMENT

Abstract INTRODUCTION 90% of spine tumor patients can develop metastases with debilitating complications, such as sensorimotor dysfunction, paralysis, and spinal instability. As spine tumor patients have limited eligibility to participate in clinical trials and have heterogenous tumor pathology, there is a distinct lack of therapeutic targets and prognostication markers of disease. Thus, there is a distinct need for molecular profiling of spine tumors. OBJECTIVE We describe an OR-to-bench-top processing of spine tumors for single-cell omic studies, with samples from a metastatic prostate cancer patient to demonstrate the ability to compare molecular markers and microenvironments of difficult-to-process spine tumors and adjacent normal tissue. METHODS Under IRB protocol #Pro00101198, patients undergoing spine surgery with the Department of Neurosurgery at Duke University were consented for tissue collection. Vertebral osseous metastases and adjacent normal tissue were confirmed histologically (H&E, immunohistochemistry) and radiologically (MRI, PET, CT, and x-ray). Tissues were manually and enzymatically homogenized in serum-free media with collagenase A and DNAse I to obtain a single cell suspension. Cells were then filter sterilized, erythrolyzed, counted to determine live-death ratio, resuspended to 10-20 million cells per mL, then cryopreserved for downstream standard library preparation for single-cell sequencing using the 10X genomics platform. Downstream analysis was performed using Seurat pipeline, InferCNV analysis, and SingleR. RESULTS P404S and PSA expression confirmed tumor was prostate in origin. Radiological imaging and H&E staining confirmed the presence of T7 osseous metastasis. Uniform manifold approximation and project (UMAP) plots identified 12 unique clusters of immune cell subpopulations between normal and tumorous vertebrae, with their own subsets of differentially expressed genes. CONCLUSION We have developed a protocol to generate granular single cell molecular profiling for spine tumors and metastases. Applications of this protocol can aid in identifying therapeutic targets, molecular predictors of disease, and potentiate increased eligibility of patients for clinical trials.

6918 A Unique Case of Oncocytic Thyroid Cancer with an NBN Gene Pathogenic Variant

Abstract Disclosure: A. Grover: None. S. Jhawar: None. S. Shekhar: None. S.A. Avadhanula: None. G. Al-Naqeeb: None. G. Thota: None. P. Veeraraghavan: None. C. Cochran: None. M.Y. Kao-Hsieh: None. A. Gharib: None. F.E. Escorcia: None. J. Del Rivero: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Oncocytic thyroid carcinoma (OTC), previously known as “Hürthle cell” carcinoma, makes up less than 5% of all thyroid cancers. OTCs are often aggressive with a high risk of metastasis, and a poorer prognosis compared to other forms of differentiated thyroid carcinoma (DTC). Molecular drivers of OTC include pathogenic variants (PVs) in NRAS, DAXX, CDKN1A, the mitochondrial genome and chromosomal alterations. PVs in the NBN gene in OTC have not been previously reported. Case: A 53-year-old male was noted to have a thyroid nodule on a routine physical examination. Patient denied any hyper/hypothyroid or compressive symptoms, and family history was unremarkable. Cytopathologic analysis of the fine needle aspiration biopsy of the nodule was consistent with a thyroid follicular neoplasm (Bethesda IV). A total thyroidectomy with central compartment neck dissection was performed. Histopathologic examination demonstrated a 7 cm x 4 cm x 4 cm OTC with capsular and lymphovascular invasion, but without extra-thyroidal extension or lymph node metastasis (pT3aN0Mx). Subsequently, adjuvant radioiodine (RAI) I131 therapy with 165 mCi was administered and post-therapy scan revealed neck uptake. One-year post-therapy RAI diagnostic scan was negative. Three years following the initial thyroid surgery, elevated serum thyroglobulin (Tg) levels were noted. A computed tomogram of the chest revealed multiple bilateral lung nodules. Further imaging ruled out involvement of other distant sites. A diagnostic lower lung wedge resection demonstrated metastatic OTC. The tumor stained positive for CK7, PAX8, TG, TTF-1 and negative for CK20 on immunohistochemistry. Next-generation sequencing of the tumor tissue (Oncomine Comprehensive Assay v3) revealed a PV in the NBN gene (c.2166_2167delGCinsAT; p.Trp722Ter). A year later, the serum Tg levels continued to rise, and the lung nodules had increased in size. Due to disease progression, lenvatinib was initiated. A [F18]-fluorodeoxyglucose positron emission tomography performed one year later demonstrated persistent pulmonary tumor burden with new osseous metastasis in the right scapula, left acetabulum, and the sternum. Zoledronic acid was initiated for the treatment of the skeletal metastases, and palliative external beam radiation (2000 cGy in 5 fractions) was administered to the sternal lesion to alleviate the bone pain. Conclusion: The NBN gene encodes for the protein nibrin, a member of the MRE11/RAD50 complex that is involved in DNA repair. PVs in NBN are commonly identified in non-thyroidal malignancies such as breast and lung carcinomas. While NBN PVs are rarely reported in DTCs, as per our knowledge, this is the first described case of OTC with a PV in NBN as the molecular driver, manifesting with an aggressive disease course. Identification of this novel PV therefore adds to the current knowledge of the molecular landscape of OTC. Presentation: 6/3/2024

6539 Hungry Bone Syndrome & Osteoblastic Metastasis In The Setting Of Prostate Cancer : A Rare Cause Of Hypocalcemia

Abstract Disclosure: B. Sharma: None. M. Khan: None. A. Rao: None. P. Guido: None. Background: Hungry bone syndrome (HBS) is due to excessive calcium and phosphorus sequestration in the bone, manifesting as hypocalcemia and hypophosphatemia.It is most commonly seen as a postoperative complication of parathyroidectomy.Advanced prostate cancer with osseous metastasis has been previously described as is a rare cause of HBS. Clinical Case: A 65 year old male was admitted to the hospital with acute congestive heart failure and severe hypocalcemia.He exhibited symptoms of muscle spasms and perioral paraesthesias. Physical exam was positive for Trousseau's sign.Initial tests were consistent with severe hypocalcemia (corrected non-ionized calcium 6.8 [8.8-10.2] mg/dL), low ionized calcium (0.58 [1.10-1.30] mmol/L). Three weeks prior to admission, corrected non-ionized calcium was 9.8 mg/mL. Other labs showed normal magnesium, normal phosphorus, elevated alkaline phosphatase (1044 [45-117] U/L), low Vitamin D (12 [>30] ng/mL ), elevated iPTH (567 [19-88] pg/mL) and low PTH-rp (9 [11-20] pg/mL]. His electrocardiogram showed regular rate and rhythm with Qtc prolongation (497 ms).He had a significant oncological history of prostate cancer and multiple myeloma in remission.He was previously treated with zoledronic acid, discontinued 1 year prior to admission, for reducing skeletal complications while being treated for multiple myeloma. He had a recent workup with medical oncology for recurrence of prostate cancer due to elevated Prostate-specific antigen (380 [<4.00] ng/mL).Computed tomography imaging showed diffuse osteoblastic metastatic disease in the axial skeleton, pelvis and proximal femur. During hospital admission hypocalcemia was persistent, likely also due to concurrent furosemide use, necessitating the administration of intravenous calcium infusion and use of cholecalciferol and calcitriol.He was discharged on calcium carbonate 4500 mg twice a day, cholecalciferol 50 000 units weekly for 12 weeks and calcitriol 2 mcg twice a day. Conclusion: Hypocalcemia in the setting of prostate cancer is most commonly due to the use of bisphosphonates or Receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitors. Hypocalcemia in this case was due to sequestration of calcium in the bone by osteoblastic metastasis. This case illustrates the importance of recognising osteoblastic metastasis as a differential in protracted and severe hypocalcemia in malignancy.High doses of calcium, vitamin D, and calcitriol replacement are often needed as the hypocalcemia is usually severe and refractory with some cases requiring prolonged IV calcium infusion.Treatment of the underlying cancer and bone metastases with chemotherapy has been shown to improve hypocalcemia and reduce the requirement of calcium and vitamin D supplementation.There is limited data to suggest if bisphosphonates can be safely used in these cases for prevention of skeletal related events. Presentation: 6/1/2024

8104 Rare Case Of Ectopic Cushing’s Syndrome Secondary To Metastatic Parotid Pleomorphic Adenocarcinoma

Abstract Disclosure: B.S. Neutel: None. P. Manroa: None. Background: Pleomorphic adenocarcinoma of the parotid gland is a rare malignancy and ectopic ACTH secretion from these tumors is very rarely described. We report a case of ectopic Cushing’s syndrome (CS) in such a patient and describe the clinical course. Clinical Case: A 69-year-old female with left parotid pleomorphic adenocarcinoma status post surgery and adjuvant radiotherapy presented to her local hospital approximately 7 months after initial treatment with proximal muscle weakness and near-syncope. Workup revealed profound hypokalemia at 1.6 mmol/L (n 3.5-5.3 mmol/L) along with new-onset hypertension (BP 175/110 mm Hg) and hyperglycemia with a HbA1c 6.5 % (n <5.7%), as well as metabolic alkalosis with a bicarbonate level of >40 mmol/L (n 22-32 mmol/L). A CT scan showed multiple liver metastases and a biopsy confirmed metastatic parotid pleomorphic adenocarcinoma. She was then transferred to our comprehensive cancer center for further management. She reported muscle weakness, easy bruising, and facial edema. She denied acne, hirsutism, or abdominal striae. Endocrine workup revealed a random cortisol of 56 mcg/dL (n 3-18 mcg/dL) and ACTH of 378 pg/mL (n 7.2-63.3 pg/mL). Her AM cortisol level remained unsuppressed at 79.2 and 59.4 mcg/dL (n< 1.8 mcg/dL) after 1 mg and 8 mg overnight dexamethasone suppression tests respectively. Late-night salivary cortisol was 7.9 mcg/dL (n <0.112 mcg/dL). An MRI of the sella was negative for any pituitary lesions. After stabilizing her clinical condition and correcting electrolyte abnormalities, she was started on chemotherapy with paclitaxel and carboplatin by the oncologist. Based on clinical suspicion of ectopic CS, ketoconazole was started and titrated upwards with rapid improvement of blood pressure, hypokalemia, and hyperglycemia. She was discharged home and antihypertensives were tapered off. ACTH staining on the liver biopsy was unable to be performed due to paucity of the specimen. A Ga-68-DOTATATE PET CT revealed increased radiotracer uptake in the liver lesion suggestive of SSTR 2 receptor positivity. Despite initial clinical improvement, her disease progressed with widespread liver, lymph node, and osseous metastases within 3 months necessitating escalating doses of ketoconazole, spironolactone, and potassium supplementation. The patient elected to pursue hospice care due to intolerance to chemotherapy and passed away shortly afterward. Conclusion: Although ectopic CS caused by parotid pleomorphic adenocarcinoma is rare, prompt recognition and treatment is necessary because ectopic ACTH production is associated with poor prognosis in these patients. Presentation: 6/3/2024

Immunotherapy and PD-L1 Tumor Expression in Moroccan Non-Small Cell Lung Cancer Patients with Various Metastasis.

The question of whether tumor expression of PD-L1 and the presence of distant metastasis could influence the efficacy of immunotherapy represents a major challenge and needs to be further elucidated. The aim of this study is to evaluate the predictive significance of tumor expression of PD-L1 as well as the number and site of metastasis in non-small cell lung cancer (NSCLC) among Moroccan patients treated with immunotherapy. Between January 2019 and February 2023, we recruited Moroccan patients with metastatic NSCLC. All were treated with immunotherapy, either as monotherapy or in combination with chemotherapy. Immunohistochemistry was used to assess PD-L1 (clone 22C3) and ALK (clone D5F3) status. EGFR status was established by qPCR. Tumor PD-L1 expression was classified into 2 levels: TPS <1% (negative expression) and TPS ≥1% (positive expression). Statistical analysis was performed using SPSS Statistics V.21 software. The median age of patients (N=40) was 67 years (39- 92 years) and the sex ratio was 9. Disease dissemination revealed that 22.5% (N=9) of patients had a metastatic burden ≥ 3 (MB≥3). As for the sites of metastasis, the results showed that 20% (N=8), 10% (N=4), 42.5% (N=17), 22.5% (N=9), 27.5% (N=11), 45% (N=18) and 27.5% (N=11) of patients had developed lymph node, liver, bone, brain, pleural, contralateral lung and adrenal metastasis respectively. Positive PD-L1 expression was significantly associated with shorter overall survival (OS = 17.19 vs. 28.85 months, p=0.01). High metastatic burden (MB ≥ 3) was associated with lower objective response rate (ORR), shorter progression-free survival (PFS), and reduced OS, respectively (ORR = 0 vs. 58.06%, p=0.002; PFS = 10.23 vs. 25.27 months, p=0.001; and OS = 11.60 vs. 27.91 months, p=0.003). Only the presence of osseous metastasis was significantly associated with lower ORR, shorter PFS, and OS compared to other metastatic locations (ORR = 5.88 vs. 73.9%, p=0.000; PFS = 10.72 vs. 31.33 months, p=0.000; and OS = 11.39 vs. 36.17 months, p=0.000). Finally, the presence of hepatic metastasis was significantly associated with shorter PFS (10.75 months) compared to those without hepatic metastasis (22.53 months) (p=0.046). Finally, the results of the multivariate analysis revealed that the presence of bone metastasis was strongly correlated with a significant decrease in progression-free survival (p=0.001) as well as overall survival (p=0.002). Our results suggest that tumor expression of PD-L1 and metastatic burden should play a significant role in predicting the response to immunotherapy. Furthermore, it is important to note that the presence of osseous and hepatic metastasis could negatively influence the clinical outcomes of immunotherapy.

131I-mIBG Therapy in the Management of High-Risk Neuroblastoma: A Retrospective Study from a Tertiary Level Hospital in South India

Abstract Introduction Neuroblastoma is the most common extracranial solid tumor in childhood. The data on the treatment experience with 131iodine-meta-iodo-benzyl-guanidine (131I-mIBG) and clinical outcome data are meager from India. Objectives This article studies the efficacy and treatment outcomes in patients treated with 131I-mIBG in high-risk neuroblastoma. Materials and Methods The study group consisted of 201 consecutive patients (aged between 1 and 15 years) with biopsy-proven neuroblastoma who underwent 131I-mIBG scans from 2012 to 2022. The majority of these children had a disease that was inoperable or had poor response to chemotherapy. Patients with positive scintigraphy were considered for therapy with 131I-mIBG. The findings were analyzed and correlated with the final diagnosis and outcomes obtained from survival during follow-up and reviewing patient records. Results Thirty-nine children, 22 males and 17 females, with a median age of 4 years had positive 131I-mIBG scintigraphy. Intra-abdominal primary lesions and osseous lesions were the most common sites of uptake on 131I-mIBG scan. Of these, 13 had upfront chemotherapy and 26 had surgery followed by chemotherapy. All the patients underwent therapy with 131I-mIBG. Fourteen patients had multiple therapies while the remaining 25 had only one therapy. Eight patients had no follow-up, and 13 had disease relapse. The remaining 18 had regression of disease which was confirmed by follow-up 131I-mIBG scintigraphy and with bone scintigraphy in patients with osseous metastases. Conclusion 131I-mIBG scintigraphy should be preferred in intermediate and high-risk neuroblastoma to know the extent of the disease and also for patient selection for early therapy with 131I-mIBG. It holds significant utility in the management of metastatic neuroblastoma, facilitating palliative pain relief and tumor size reduction in inoperable or metastatic disease.

A case series of osseous metastases in patients with glioblastoma.

Extracranial metastases occur in <2% of cases of glioblastoma (GBM). When metastases do occur, bone is the most common destination. Herein, we review clinical characteristics of GBM patients with osseous metastases and evaluate both potential risk factors and prognostic significance. Using an institutional database, we identified and retrospectively analyzed 6 patients with both GBM and osseous metastases. We collected data on patient demographics, tumor genetics, clinical courses, and outcomes. Given the rarity of metastatic GBM, we conducted historical comparisons using previously published literature. Five patients with osseous metastases (83%) were male, with a median age of 46 years at GBM diagnosis (range: 20-84). All patients had IDH-wildtype, MGMT promoter unmethylated GBM and 5 (83%) had alterations in TP53. All patients underwent surgical resection for GBM followed by radiation with concurrent and adjuvant temozolomide. Four patients (67%) received bevacizumab prior to bone metastasis diagnosis. Bone metastases were discovered at a median of 12.2 months (range: 5.3-35.2) after GBM diagnosis and 4.8 months after starting bevacizumab (range: 3.5-13.2). Three patients (50%) received immunotherapy. After osseous metastasis diagnosis, the median survival was 25 days (range: 13-225). In our cohort, most patients were male and young at the time of GBM diagnosis. All patients had IDH-wildtype, MGMT promoter unmethylated GBM, and most had alterations in TP53, which may be important for osseous metastasis. Most patients received bevacizumab, which has been associated with earlier metastasis. Osseous metastases of GBM occur and portend a dismal prognosis in an already aggressive malignancy.

A rare case of a solitary osseous metastasis from breast carcinoma presenting with fluid-fluid levels on MRI.

Osseous metastatic disease is commonly encountered in breast carcinoma, which typically presents as either osteolytic, osteoblastic, or mixed lesions on imaging. Osseous metastasis presenting as a multiloculated cystic lesion with fluid-fluid levels resembling that of an aneurysmal bone cyst (ABC) is sparsely described in the literature, and even less so in the case of breast carcinoma. We report an unusual case of fluid-fluid levels in a bone metastasis to the spine in a 66-year-old female with a prior history of breast carcinoma. Magnetic resonance imaging (MRI) demonstrated a cystic lesion with fluid levels resembling that of an ABC. Computed tomography (CT)-guided biopsy revealed the lesion to be a metastasis from breast carcinoma. The management of ABCs and osseous metastases differ drastically. Accurate diagnosis and distinction between these lesions is paramount as the management of metastatic disease can have a significant impact on the quality and length of life. The presentation, differential diagnoses and imaging features of this atypical case are discussed.

DIPG-78. OSSEOUS METASTASIS IN DIFFUSE MIDLINE GLIOMA: A CASE REPORT AND REVIEW OF LITERATURE

Abstract BACKGROUND Diffuse midline glioma (DMG), H3K 27M-altered are uniformly fatal CNS tumors with 2-year overall survival of less than 10%. Neuroaxis dissemination with disease progression is well known. However, osseous metastasis is a rare occurrence. METHODS We report a patient with localized DMG at diagnosis with subsequent craniospinal and osseous metastasis. We also performed an updated literature review on DMG with extra-neural metastasis (ENM). RESULTS At 11 years of age, the patient presented with progressively worsening headache and vomiting and was found to have a tumor within the right thalamus with mild mass effect on the right lateral ventricle without hydrocephalus. The patient underwent stereotactic tumor biopsy with pathology consistent with DMG, H3K 27-altered. Whole exome sequencing revealed alterations in H3-3A, TP53 and PTPN11. Treatment consisted of upfront focal radiation therapy with subsequent stabilization of the thalamic lesion. However, within 1.5 months of completing radiotherapy, the patient developed drop metastasis, intracranial leptomeningeal dissemination, and diffuse osseous metastasis within the spine, bilateral iliac wings, and ribs. The patient died from disease progression within 2 months of metastatic progression, 6 months from initial diagnosis. Review of literature yielded 11 cases of ENM in pediatric patients with DMG, H3K 27M-altered. Four patients had ENM at diagnosis. The remaining seven patients developed extra CNS metastasis within 1-6 months of diagnosis. Eight patients received upfront radiotherapy with variation in adjuvant chemotherapy. All patients died with median overall survival of 9 months (range, 0.5-24) from diagnosis and 6 months (range, 0.5-22) from ENM occurrence. CONCLUSION ENM in DMG, H3K 27-altered is uncommon. Mechanisms for development of ENM in DMG is unclear. Biopsy and molecular testing for both primary site and ENM should be considered to help elucidate biologic mechanisms of ENM and potentially guide management.

Ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis: a case report

BackgroundThe diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare.Case presentationA 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis.ConclusionPhysicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.

Parathyroid hormone related-protein (PTHrP) in tissues with poor prognosis in prostate cancer patients.

Parathyroid hormone-related peptide (PTHrP) is known to have a pivotal role in the progression of various solid tumors, among which prostate cancer stands out. However, the extent of PTHrP expression and its clinical implications in prostate cancer patients remain shrouded in obscurity. The primary objective of this research endeavor was to shed light on the relevance of PTHrP in the context of prostate cancer patients and to uncover the potential underlying mechanisms. The expression of PTHrP, E-cadherin, and vimentin in tumor tissues of 88 prostate cancer patients was evaluated by immunohistochemical technique. Subsequently, the associations between PTHrP and clinicopathological parameters and prognosis of patients with prostate cancer were analyzed. Immunohistochemical analysis showed that the expression rates of PTHrP, E-cadherin, and vimentin in prostate cancer tissues were 95.5%, 88.6%, and 84.1%, respectively. Patients with a high level of PTHrP had a decreased expression of E-cadherin (P = .013) and an increased expression of vimentin (P = .010) compared with patients with a low level of PTHrP. Besides, the high expression of PTHrP was significantly correlated with a higher level of initial prostate-specific antigen (P = .026), positive lymph node metastasis (P = .010), osseous metastasis (P = .004), and Gleason score (P = .026). Moreover, patients with a high level of PTHrP had shorter progression-free survival (P = .002) than patients with a low level of PTHrP. The present study indicates that PTHrP is associated with risk factors of poor outcomes in prostate cancer, while epithelial-mesenchymal transition may be involved in this process.

Pearls and Pitfalls in Applying PI-RADS 2.1

AbstractThe use of Prostate Imaging Reporting and Data System (PI-RADS) with multiparametric magnetic resonance imaging (MRI) has significantly improved the detection of clinically significant prostate cancer (csPCa), but there are certain challenges that the reader may face. This review provides an overview of the pitfalls associated with the PI-RADS system for multiparametric prostate MRI (mpMRI), with suggestions/pearls to help overcome these pitfalls.PI-RADS assessment is hindered by several causes of false positives (FPs) and false negatives (FNs). In addition, there is wide variability in the positive predictive value (PPV) of the PI-RADS system across different centers, highlighting the need for improvement. While the negative predictive value (NPV) for csPCa is generally high, variations exist.This review discusses the pitfalls contributing to FNs, including MRI artifacts, such as susceptibility and motion artifacts. Techniques to optimize image acquisition, such as switching the phase encoding direction and reducing bowel peristalsis, are suggested to mitigate these artifacts. Improper b-value selection for diffusion-weighted imaging (DWI) is another pitfall, emphasizing the importance of using high b-values (≥1,400 s/mm2) to optimize neoplasm detection. Similarly, optimizing window settings to visualize csPCa, correctly positioning the endorectal coil, awareness of rare variants like mucinous adenocarcinoma and cribriform adenocarcinoma, and distinguishing central zone tumors from normal central zone are discussed.This article highlights the common pitfalls causing FPs, such as benign pathologies like prostatitis, granulomatous prostatitis, prostatic abscess, stromal BPH nodules, extruded BPH nodules, and prostatic calcifications. It also discusses the pitfalls related to normal anatomical structures, including the central zone, anterior fibromuscular stroma, thickened surgical capsule, neurovascular bundle, and periprostatic venous plexus. Techniques for carefully evaluating these entities' morphology and distribution of signal abnormalities are described to avoid overdiagnosing these as PCa. The article also addresses the pitfalls related to postintervention changes, including postbiopsy hemorrhage and artifacts caused by the UroLift procedure, while providing recommendations for managing these challenges.Finally, the pitfalls that may be encountered during staging, including evaluation for extraprostatic extension, and pelvic nodal and osseous metastases, are highlighted.

Real world outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177-PSMA-vipivotide tetraxetan (Lu177-PVT).

86 Background: Lu177-PVT is a novel radioligand, which was recently approved by the FDA to treat mCRPC. Real world data on its use and efficacy is limited. We aimed to build a new retrospective cohort of patients with mCRPC treated with 177Lu PSMA-617 in order to investigate clinical and pathological variables associated with treatment responses. Methods: We identified patients with a confirmed diagnosis of prostate cancer and were treated at Stanford University Medical Center with at least one dose of Lu177-PVT including trial patients. Data collection included demographic, clinicopathological and outcome variables. Statistical analysis was performed using Chi-squared and log-rank Kaplan-Meier analysis. Results: We identified 85 patients who met study criteria and were treated between March 2021 and June 2023, the median age was 66, 33% were non-white, median PSA at treatment initiation was 60, and 94% had osseous metastasis. Patients were pretreated with a median of six lines (range: 1-10) of prior therapy including local therapies; prostatectomy (28%), radiation (61%), brachytherapy (11%), taxane (78%), immunotherapy including checkpoint inhibitor and Sipuleucel-T (24%), PARP inhibitor (6%), and Radium-223 (15%). A majority of patients also received prior germline or somatic genetic testing (79%), with homologous recombination germline and somatic deficiencies present in 13% of patients. Of the identified cohort, 19 patients were still undergoing active treatment with Lu177-PVT at the time of data collection. Of the 66 patients not currently undergoing active Lu177-PVT treatment, 29 patients discontinued treatment due to progressive disease (44%) and 14 (21%) to toxicity related to 177Lu PSMA-617, completing a median of 4 cycles. 47 patients (71%) had an overall decline in their PSA from baseline, with 32 patients (49%) experiencing a decrease greater than fifty percent. Median overall survival of patients not actively receiving 177Lu PSMA-617 treatment was 366 days. Age, previous lines of therapy, and median time from diagnosis were not predictive of PSA treatment response (greater than fifty-percent reduction from baseline PSA). Conclusions: Lu177-PVT is a promising treatment for mCRPC in patients. Our results confirm ‘real-world’ activity of Lu177-PVT and align well with VISION study results, though real-world overall survival was comparatively shorter (12 months vs 15 months in VISION trial). Further investigation is warranted into predictors of response and toxicity.

Assessment of hematological toxicity in patients with advanced neuroendocrine tumors and extensive/innumerable bone metastases undergoing lutetium-177 DOTATATE treatment.

592 Background: The introduction of peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) DOTATATE has led to a paradigm shift in the treatment of neuroendocrine tumors (NETs). Hematological toxicity is a well-recognized adverse effect (AE) of 177Lu DOTATATE. Most cytopenias are transient, with an estimated incidence of 10-25%, typically mild to moderate in severity (grade G1-2). The most dreaded AE of PRRT is therapy-related myeloid neoplasm (t-MN), with an estimated 2-8% incidence and a higher incidence reported in patients who also received prior chemotherapy. We sought to evaluate the hematological safety of 177Lu PRRT in the setting of NETs with extensive (i.e., innumerable) bone metastases. Methods: We retrospectively reviewed the medical records of all Mayo Clinic patients (pts) with extensive/innumerable osseous metastases, defined as &gt;50% skeletal involvement by positron emission tomography (PET) DOTATATE, who were treated with 177Lu DOTATATE. Pts characteristics and laboratory results were collected before, during, and after 177Lu DOTATATE treatment. Hematotoxicity was graded according to the NCI-CTCAE v5. Results: Out of 27 pts, 13(48%) developed cytopenia(s) of any grade after treatment with one or more cycles of 177Lu DOTATATE. In total, there were 13(48%) pts with anemia, 13(48%) with thrombocytopenia, and 6(22%) with neutropenia. Six (22%) pts had severe hematological toxicity (G3-4). Twelve months post-PRRT, 7(26%) pts continued to experience cytopenia(s) of any grade, of whom 4(15%) had G3-4 hematotoxicity. One pt developed t-MN, and two pts had myelophthisis on bone marrow biopsy from infiltrating NET. 16(59%) pts received cytotoxic chemotherapy before PRRT, and 7(25.9%) developed subsequent cytopenia(s). Overall, 15(55%) pts completed four cycles, while 3 pts didn’t complete four cycles of 177Lu DOTATATE due to hematotoxicity. Conclusions: Pts with advanced NETs and extensive/innumerable bone metastases treated with PRRT could be at higher risk for myelosuppression than historical controls. Our study highlights the importance of carefully monitoring and assessing hematological parameters in pts being considered for 177Lu DOTATATE with extensive/innumerable bone metastasis. [Table: see text]

18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography and 68Ga-prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging in the Evaluation of Rare Entity Adult Embryonal Rhabdomyosarcoma of Prostate.

A 21-year-old male with embryonal rhabdomyosarcoma of the prostate was referred for 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and 68Ga-prostate-specific membrane antigen (PSMA) PET/CT for initial disease staging. The PET scans revealed hypermetabolic and PSMA expressing lobulated mass involving both lobes of the prostate and weakly metabolic and PSMA expressing few bilateral pararectal and external iliac nodes, multiple bilateral lung nodules scattered over the lung parenchyma and multiple bone marrow lesions in both axial and appendicular skeleton. Magnetic resonance imaging prostate showed gross prostatomegaly with large lobulated T2 hyperintense heterogeneously enhancing mass lesion showing restricted diffusion, involving both lobes of the prostate with extraprostatic spread along anterior, posterior, and left lateral margins with evidence of lymph nodal and osseous metastases. The demonstration of increased uptake of 18F-FDG and 68Ga-PSMA in the primary as well as bilateral pararectal and external iliac nodes, multiple bilateral lung nodules, and multiple bone marrow lesions in both axial and appendicular skeleton indicates a potential role of 18F-FDG PET/CT and 68Ga-PSMA PET/CT in disease staging in this rare aggressive tumor of the prostate.

Long-term control with immunotherapy and aggressive re-irradiation for basal cell carcinoma metastatic to the vertebra: A case report and literature review of rare osseous metastasis

BackgroundCutaneous basal cell carcinoma (BCC) is a prevalent malignancy with a rising incidence, though it rarely metastasizes, with an incidence of 0.0028–0.5 %. Hematogenous metastatic BCC (mBCC) is particularly rare and associated with a median survival of 8–14 months. Case detailsThis case report details a 59-year-old male with a primary BCC on his left shoulder metastasizing to the lungs and spine. Despite aggressive multimodal treatment, including surgery, radiation, and systemic therapy with hedgehog inhibitors (vismodegib, sonidegib), the disease progressed. At 55 months post-diagnosis, pembrolizumab was introduced due to the high tumor mutation burden (TMB-H), resulting in a notable therapeutic response and prolonged survival. The patient underwent extensive follow-up, including re-irradiation of spinal metastases and immunotherapy, maintaining stable disease for over 101 months. Results/literature reviewA systematic literature review identified only 26 cases of osseous mBCC, primarily treated with surgery and radiation, with variable survival outcomes. This case stands out due to its prolonged survival and novel use of pembrolizumab, highlighting the potential role of immunotherapy in TMB-H mBCC. The patient’s TMB-H status likely contributed to the favorable response to immunotherapy. ConclusionThis report underscores the importance of genetic profiling in mBCC to identify candidates for emerging immunotherapy treatments. The findings suggest that patients with high mutational burden mBCC may benefit from pembrolizumab, offering a new therapeutic avenue for this rare osseous metastasis.

Abstract 17945: Characterization and Treatment of Primary Cardiac Rhabdomyosarcoma in the Last Three Decades

Introduction: Cardiac rhabdomyosarcomas are rare, aggressive neoplasms comprising 5% of cardiac sarcomas overall. Due to the low prevalence, there is little consensus on the appropriate identification and treatment of this condition. This research aims to characterize trends in the clinical presentation of the disease and identify improvements for therapeutic management. Methods: A literature review was conducted by identifying cases of primary cardiac rhabdomyosarcoma published in English to PubMed between 1993 and 2023 and available via the SUNY Downstate Library. Studies were analyzed for patient demographics, clinical course, treatment, and recovery. Results: The analysis included 31 identified cases. Most cases were reported in male (52%) adults (87%) with an average age of 44 (STD: 21). Patients frequently presented with dyspnea (59%) and cardiac issues (52%), including chest pain (19%) and conduction disorders (19%). Tumors were detected via echocardiogram (79%) and CT (18%) and frequently left-sided (60%), with the most cases arising in the left atrium (47%). There was valvular involvement in 43% of cases. Surgery was performed in 86% of patients, of which 33% were fully resected via sternotomy and 13% were cardiac transplants for unresectable tumors. 56% of patients survived at 12 months follow-up. Surgical management was combined with chemotherapy (46%), such as the VAC regimen (40%), and radiation (14%), which improved patient 1-year mortality by 26%. 26% of patients developed recurrence of the primary tumor and 42% of patients developed metastatic disease; osseous metastases (38%) were the most common. 13% of patients had a prior history of cancer. Conclusions: The rare rhabdomyosarcoma may present as a middle-aged patient with dyspnea and cardiac concerns refractive to standard management. A left atrial mass mimicking a benign lesion such as a myxoma may be seen on echocardiogram, and suspicious lesions should undergo surgical resection to relieve symptoms and confirm the diagnosis. Supplementation of surgical management using chemotherapy and radiation may improve outcomes in patients. Clinicians should closely monitor the patient for osseous and lung metastases. A prior history of cancer may be a risk factor for the disease.

The low and disproportionate utilization of antiresorptive therapy in patients with osseous metastasis

IntroductionAntiresorptive therapies are commonly utilized to mitigate and prevent skeletal-related-events in patients with metastatic osseous disease. However, limited data exists on the incidence or factors associated with prescription of antiresorptives or their effects on the incidence of pathologic fractures in patients with osseous metastatic disease. The aims of this study were to determine 1) the proportion of patients with osseous metastasis who receive antiresorptive therapy and sustain a pathologic fracture within 2-years of a new diagnosis, 2) factors associated with sustaining a pathologic fracture, and 3) factors are associated with the likelihood of receiving antiresorptive therapy. MethodsBetween January 2010 and October 2021, 1,492,301 patients with a new diagnosis of osseous metastasis were captured in the Mariner dataset of the PearlDiver database. Patients were identified using International Classification of Disease (ICD) 10 codes for osseous metastasis. We excluded patients with a prior diagnosis of osseous metastasis and if they had less than two-years of follow-up. There were 696,459 patients (46.7 %) included for analysis. Of these patients, 63 % (N = 437,716) were over the age of 65, 46 % were women, and 5.6 % had Medicaid insurance. We identified patients who were prescribed antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis. Cox proportional hazard ratio models were created to predict factors associated with 1) pathologic fracture and 2) receiving antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis, respectively. ResultsThe incidence of antiresorptive therapy prescription was 7.7 % in our cohort. The incidence of pathologic fracture within 2-years of a new diagnosis was 7.3 %. The risk of sustaining a pathologic fracture was higher for patients aged 35–44 (HR 1.27 [95 % CI 1.08–1.51]; p = 0.004), those with primary kidney cancer (HR 1.78 [95 % CI 1.71–1.85]; p < 0.001), p = 0.005), multiple myeloma (HR 2.49 [95 % CI 2.39–2.59]; p < 0.001), and Medicaid insurance (HR 1.17 [95 % CI 1.13–1.21]; p < 0.001). The risk of sustaining a pathologic fracture was lower for patients on antiresorptive therapy (HR 0.71 [95 % CI 0.66–0.83]; p < 0.001). Increasing age was an independent predictor for antiresorptive therapy prescription (HR 1.77–16.38, all p < 0.05). Male sex as well as diagnosis of primary prostate, lung, or kidney cancer and Medicaid insurance were negative predictors for antiresorptive prescription (HR 0.15–0.87, all p < 0.001). ConclusionsThe utilization of antiresorptive therapy in patients with osseous metastases remains unacceptably low, with only 7.7% patients being prescribed these therapies, despite shown efficacy in reduction of pathologic fractures incidences. This study identified younger patients, males, and those diagnosed with primary prostate, kidney, and lung cancers to be at increased risk of not being prescribed antiresorptive therapy, suggesting possible bias in prescription patterns. Greater efforts are needed by providers who care for this vulnerable population to increase the utilization and reduce disparities of prescribing antiresorptive therapy.

SAT553 A Case of Metastatic Functional Papillary Thyroid Cancer in the Setting of Graves’ Disease

Abstract Disclosure: N. Manuel: None. S.J. Sternlieb: None. J. Dendy: None. Q.Z. Iqbal: None. A Case of Metastatic Functional Papillary Thyroid Cancer In the Setting of Graves’ DiseaseManuel, N., Sternlieb, S., Grissett, B., Iqbal, Q., Dendy, J. Background: Grave’s disease (GD) and papillary thyroid cancer (PTC) can be concomitant diseases. We report a rare case of metastatic PTC with concomitant GD leading to symptomatic hyperthyroidism despite total thyroidectomy. Clinical Case: A 58-year-old woman with longstanding history of thyroid nodules and left dominant nodule with benign biopsy on multiple occasions presented to her PCP with dyspnea, weight loss and globus sensation. CT of the chest was obtained revealing tracheal deviation from neck mass, mediastinal lymphadenopathy and multiple pulmonary nodules. Biopsy of lung nodule showed follicular features consistent with tumor cells of thyroid origin. She had a total thyroidectomy with central neck dissection with a final diagnosis of left sided 5 cm infiltrative follicular variant papillary thyroid carcinoma. Thyroid hormone replacement was initiated and on follow up 4 weeks later she was noted to be tachycardic at weight-based dose. At that time TSH was &amp;lt;0.010 uIU/mL (0.400 - 4.00), free T4 was 1.96 ng/dL (0.71 – 1.51) and Thyroglobulin was found to be 31516 ng/dL (Athyrotic &amp;lt;0.1). Prior to planned RAI she developed symptoms of dyspnea on exertion and edema and was sent to the ER for abnormal D. Dimer. Workup for PE was negative including CTA of the chest. A follow up visit showed further symptoms of hyperthyroidism with worsening fatigue, dyspnea, palpitations and new onset tremor. Levothyroxine dose was decreased further but 2 weeks later she returned to the ER with worsened thyroid function tests, and she was admitted for symptomatic hyperthyroidism. Levothyroxine was held and she was placed on PTU and propranolol. Given the overt symptomatic hyperthyroidism there were concerns for either Jod-Basedow phenomenon from iodine load with recent imaging or for hyperfunctioning PTC metastasis as the cause. Thyrotropin receptor antibody level was checked to further clarify and was elevated at 22 IU/L (0.00 – 1.75) consistent with GD. An I-131 diagnostic whole-body scan demonstrated small foci of right thyroid bed remnant and iodine-avid metastases involving mediastinal nodal disease as well as pulmonary and osseous metastases. She then underwent RAI therapy with 104.5 mCi I-131 without Thyrogen stimulation. Follow up whole body scan showed persistence of iodine-avid metastasis without any new foci of uptake compared to pretreatment scans. Conclusion: Although the coexistence of them is rare, GD should be put into the differential of rapidly progressive metastatic PTC especially if patient markedly hyperthyroid on lower doses of thyroid hormone. While functional thyroid carcinoma is rare, with less than 100 cases in literature, thorough investigation should be completed in order to not miss this concomitant disease process. Presentation Date: Saturday, June 17, 2023

SAT563 Follicular Thyroid Cancer Masquerading as Chest Wall Mass With an Aggressive Course

Abstract Disclosure: I. Goyal: None. E. Punni: None. L. Adhikari: None. Introduction:Follicular thyroid cancers (FTC) are more aggressive than papillary thyroid cancer and usually have more advanced tumor stage at the time of presentation. Musculoskeletal metastases are rare though, but when present can cause various complications like pathological fractures and nerve compression. Clinical case:A 75-year-old female was seen in orthopedics clinic for a left infraclavicular chest wall mass. MRI chest showed a large destructive mass invading the manubrium. Biopsy showed follicular cells consistent with ectopic thyroid tissue. CT neck/chest showed 2x1.8 cm right thyroid lobe nodule and left sternoclavicular joint metastasis. She underwent total thyroidectomy and resection of portions of manubrium, left clavicle and left 1st and 2nd rib. Pathology showed FTC in right thyroid lobe, measuring 2.6 cm in greatest dimension with angioinvasion, and FTC of manubrium, adjacent connective tissue and sternoclavicular joint and ribs, measuring 6.3 cm in greatest dimension. Pathological TNM staging was pT2N0M1. Her 6-week post-op thyroglobulin (Tg) level was 28.7 ng/mL (Beckman Coulter Immunometric Assay, reference value &amp;lt;0.1 athyrotic). She was started on levothyroxine supplementation to achieve a TSH &amp;lt;0.01 uIu/mL. She was subsequently treated with 200 mCi of radio-active iodine (RAI) as adjuvant therapy. Post-therapy whole body scan showed increased activity in the right strap muscle and iodine-avid osseous metastasis in right hemisacrum. She further received radiation therapy to neck and sternal regions, and the right sacroiliac joint. Following this, patient was monitored with serial Tg panel and neck ultrasound (US). Her initial post-op US neck showed a soft tissue fullness in right thyroidectomy bed, concerning for residual disease but this was no longer seen after 3 months. Her Tg level downtrended from 28.7 ng/mL to 12.6 ng/mL and further to 1.8 ng/mL at 1-year follow-up. However, her course was complicated by development of several oral ulcers resulting from high-dose RAI therapy which were treated symptomatically with hydration, topical analgesics and Listerine mouth washes. The patient reported ongoing bowel incontinence since her initial cancer diagnosis. MRI pelvis showed rim-enhancing 4.5cm lesion centered at right sacral ala and extending into adjacent S1/S2 neural foramina. She was re-referred for palliative radiation therapy.Conclusion:This case of FTC is unique due to its uncommon initial presentation. Skeletal metastases to sacrum resulted in bowel incontinence in our patient. When present, skeletal metastases need treatment with high-dose (200 mCi) RAI. RAI therapy can cause xerostomia, hypogeusia and sialadenitis due to reductions in salivary flow. Clinicians should be aware of the early and late-onset complications of RAI therapy, discuss these with the patient before therapy and manage the complications adequately if these occur. Presentation Date: Saturday, June 17, 2023