American College of Nuclear Medicine (ACNM) 2022 ACNM Annual Meeting Abstracts

The proceedings contain 91 papers. The topics discussed include: the new approach of COVID-19 patients with deteriorating respiratory functions using perfusion SPECT/CT imaging;increasing interest in nuclear medicine: evaluation of an educational workshop;cost-benefit analysis recommends further utilization of cardiac PET/MR for sarcoidosis evaluation;development of a nomogram model for predicting the recurrence of differentiated thyroid carcinoma patients based on a thyroid cancer database from a tertiary hospital in China;multi-center validation of radiomic models in new data using ComBat-based harmonization of features;bone scan with Tc99m-MDP, the missing link in the initial staging of muscle-invasive bladder carcinoma;and comparison of absorbed doses to kidneys calculated employing three time points and employing two time points in neuroendocrine patients undergoing Lu-177 DOTATATE therapy using planar images.

Clinical Outcomes of Stage III Non-small Cell Lung Cancer Patients Treated With Radical Radiotherapy in a Institution in Brazil

Introduction: Lung cancer is the leading cause of cancer death. Most cases are diagnosed at advanced stages. Stage III cancers are treated in a curative manner, despite the low success rate. Our objective was to define the clinical and epidemiological profile of stage III non-small cell lung cancer (NSCLC) patients (pts) treated with radiotherapy (RT) and their response to therapy. Method(s): It is a retrospective and observational study of all non-surgical stage III NSCLC pts treated with RT with curative intent at a public cancer center in the south of Brazil between January/2016 and June/2022. Data collected: dates of biopsy, treatment initiation, image progression or relapse, death and last registration;ECOG-PS;sex;smoking status;histology;stage (TNM 7th Ed) and chemotherapy (CT) use. Survival analysis were performed using the Kaplan-Meier method and factors associated with the events were analyzed using Cox regression. Groups were compared with chi-square and Kruskal-Wallis tests. Result(s): Eighty-seven pts were identified;median age 63 years-old;46 (52%) male, 78 (90%) former or present smokers;51 (62%) ECOG-PS 0/1;49 (58%) squamous (sq) histology;48 (60%) stage IIIb;60 (68%) had abdomen, bone and brain scans;64 (73%) had concurrent CT, 11(13%) sequential and 12 (14%) exclusive RT;64 (74%) concluded RT;53 (60%) had disease progression or relapse and 47 (54%) died. It took a median of 77 days (d) from biopsy to treatment initiation, without difference between pre or during COVID-19 pandemic. The follow-up was of 305d, progression free survival 192d and overall survival 253d (median for all), using the treatment initiation as baseline date. Younger pts and ECOG-PS 0/1 pts were more commonly treated with concurrent CT (X2:8,87;p 0,0054 and X2:10,82;p 0,004 respectively). No factor influenced progression free survival on uni or multivariable analyses. Factors correlated with overall survival on univariable analysis were: ECOG-PS (hazard ratio (HR) 2,02;p 0,010);bone scan (HR 0,5;p 0,028);treatment conclusion (HR 3,53;p<0,0001). Multivariable analysis: ECOG-PS (HR 2,95;p 0,017), non-sq histology (HR 2,26;p 0,044);RT conclusion (HR 4,69;p<0,0001). Conclusion(s): Our study shows shorter overall and progression free survival than literature, with a large portion of patients being treated with ECOG-PS of 2 or greater and without adequate systemic staging. About one-quarter of patients did not conclude the treatment, and this was the most negative factor impacting survival next to ECOG-PS.Copyright © 2023

Lorigerlimab, a bispecific PD-13CTLA-4 DART molecule in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A phase 1 expansion (exp) cohort

Background: Lorigerlimab (MGD019) is an investigational, bispecific Fc-bearing (IgG4) DART molecule designed to enhance CTLA-4 blockade on dual expressing, tumor infiltrating lymphocytes, while maintaining maximal PD-1 blockade on PD-1 expressing cells. Lorigerlimab has approximate dose proportional PK across 1-10 mg/kg IV dosing Q3W, with sustained PD-1 receptor occupancy evident at doses >=1 mg/kg Q3W. MGD019-01 is a global first-in-human dose finding and activity estimating study of lorigerlimab in advanced solid tumors (AST). Method(s): The exp phase of MGD019-01 evaluates single agent safety, PK, and antitumor effects of lorigerlimab at the recommended dose for exp of 6 mg/ kg IV Q3W in 4 tumor specific cohorts. Confirmed responses were noted in each cohort. Preliminary results of the mCRPC cohort are reported here. Response evaluable pts received >=1 dose and had >=1 postbaseline imaging evaluation. Measurable lesions were evaluated per RECIST v1.1 and skeletal metastases assessed by bone scan. Prostate specific antigen (PSA) response was defined as a >=50% (PSA50) or>=90% (PSA90) PSA decline from baseline with confirmation>=3 weeks later. Expression of proliferation marker, Ki67, and inducible costimulator (ICOS) by peripheral T cells was assessed by flow cytometry. Result(s): At data cutoff (9/10/22), 127 pts with AST received >=1 dose of lorigerlimab 6 mg/ kg. Median exposure was 10 weeks (range, 0.1, 94.4) with median of 4 infusions. 6 pts remain on therapy;36 discontinued for PD (n=13), AEs (n=17), or patient/physician decision (n=6). Treatment related adverse events (TRAE) occurred in 109/127 (85.8%) pts. TRAEs occurring in>=15% of pts were fatigue, pruritus, hypothyroidism, pyrexia. Rates of grade >=3 TRAEs and immune-related AEs were 32.3% and 7.9%, respectively. AEs leading to drug discontinuation occurred in 22.8% of pts. There were no fatal AEs related to lorigerlimab. In the mCRPC exp cohort (n=42), pts had a median of 2 prior lines of therapy for CRPC, >80% received prior ART or taxanes;88% had visceral (liver, 26%;lung, 26%) or nodal disease and 95% had bone metastases. 42 pts were PSA response evaluable;35 were RECIST evaluable. ORR was 25.7% (9/35;9 confirmed PRs). Median duration of response was 16.1 weeks (range 6-25+ weeks). 5 responders remain on study, 4 discontinued for unrelated fatal AEs: COVID-19 (2) cardiac arrest (1) C. difficile infection (1). Confirmed PSA50 and PSA90 response rates were 28.6%(12/42) and 21.4% (9/42), respectively. Increased frequencies of Ki67+ and ICOS+ T cells were observed on day 8 posttreatment compared to pretherapy per the flow cytometry analyses from 35 pts. Conclusion(s): Lorigerlimab demonstrates a manageable safety profile with evidence of encouraging and durable antitumor activity in a chemotherapy refractory mCRPC population. Randomized evaluation of lorigerlimab in mCRPC is warranted.

Accommodating ''History Effects'' in Long Duration, Multisite Clinical Trials to Ensure Relevant and Compelling Evidence

Over the course of a clinical trial, changes in the practice environment have the potential to reduce internal and external validity and impact change in patient outcomes. Such ''history effects''1 can take the form of changes in standard of care, clinical guidelines and recommendations, new drug/device availability in the marketplace, testing and screening procedures, and, as recently experienced, a global pandemic. Clinical trials conducted over many years are particularly susceptible to history effects. Such effects can impact foundational ability to continue a trial, including clinician equipoise and ability to implement trial interventions, necessitating awareness and action planning. For example, Curtis et al.2 acknowledged challenges with clinical guideline history effects and issued recommendations for addressing them such as consideration of participant wellbeing, stakeholder engagement, safety monitoring, review of guideline and policy changes, and development of rules for protocol changes. This session will explore how four multisite clinical trials conducted with VA Cooperative Studies Program sponsorship and coordination have weathered history effects during prolonged periods of enrollment. Topics to be covered include the implementation of pragmatic designs, monitoring of clinical guidelines, assessing control group treatment conditions, modifying protocols, adjusting quality assurance procedures, refining recruitment pathways, and training site investigators. The speakers, Study Chairs, will describe best practices and provide recommendations for navigating history effects in prolonged multisite clinical trials that can ensure outcomes remain relevant and compelling to inform public health at trial commencement. The CSP 2008/PTXRx study is a pragmatic, randomized, double-blind, placebo-controlled, multicenter clinical trial of Veteran patients with diabetic kidney disease (DKD) examining whether pentoxifylline (PTX), when added to usual care, can delay time to end-stage renal disease or death. Enrollment for the study began in 2019, and it is anticipated that 9 years of follow-up will be required to observe the required number of primary events. Given the long duration of the study, changes in clinical guidelines were anticipated and have occurred, including the approval of new DKD therapies and introduction of a new formula for estimated glomerular filtration rate (eGFR) calculation. In anticipation of these changes, the study design allows for whatever standard of care is extant at any time during the course of the study. PTXR's pragmatic trial design and protocol leverage the VA's research infrastructure and remote platforms allowing the study to be responsive to external changes and to safely continue during a global pandemic. The CSP 596/OPTION study is a randomized, double- blind, multicenter trial of Veteran patients with a first or second recurrent Clostridium difficile infection (CDI) comparing (1) fidaxomicin and (2) vancomycin, followed by a taper and pulse to (3) a standard vancomycin regimen. Since enrollment began in 2016, significant changes in CDI epidemiology and clinical management have impacted the study. The COVID-19 pandemic also resulted in an administrative hold on all trial activity followed by staggered reopening of sites due to variable COVID-19 activity and clinical priorities. Many clinical laboratories switched to algorithms that included free toxin assays in addition to polymerase chain reaction (PCR) tests out of concern for overdiagnosis based on PCR testing alone, reducing the number of potentially enrollable cases. There has been increased empirical vancomycin treatment for recurrent CDI without confirmation by stool testing, a requirement for enrollment, and a recruitment strategy for identifying potential cases. Finally, conflicting clinical guidelines for recurrent CDI has created potential equipoise when considering enrollment. Ongoing educational efforts have been made to clarify the protocol and emphasize the validity of the research question as well as protoco changes to allow safe enrollment and follow-up of participants in the face of the ongoing COVID-19 pandemic. The CSP 2005/VALOR is a phase III randomized, open label, multicenter clinical trial of Veteran patients with operable stage I non-small cell lung cancer that compares stereotactic radiotherapy and anatomic pulmonary resection with a primary outcome measure of overall survival. The study was activated in 2017 and recruitment to the trial has been affected by ongoing changes in public and clinician perceptions about stereotactic radiotherapy and surgery that have interfered with equipoise and willingness of participants to enroll. The study team perpetually addresses this challenge through group conversations with local site investigators, study coordinators, and other research personnel to preserve group equipoise across the study. Since the study's activation, new safety information about stereotactic radiotherapy has emerged necessitating protocol modifications while aiming to preserve internal and external validity. The includes modifying standard operating procedures for the study's centralized quality assurance program that has had to adapt its process to remain contemporary. STARPORT, funded by VA CSRD with CSP collaboration, is a randomized, open label, multicenter clinical trial of Veteran patients with oligorecurrent prostate cancer comparing the effects of standard systemic therapy (SST) alone or with PET-directed local therapy using surgery or radiation. Although enrollment was initiated in 2021, changes are already evident in clinical practice guidelines regarding the use of imaging in workup in this patient population. Shortly before the start of accrual, 18F-DCFPyL PSMA PET/CT received FDA-approval. Consequently, it is being rapidly adopted at the STARPORT VA medical centers and the use of conventional imaging using CT or bone scan prior to PET/CT imaging-part of the original eligibility criteria-quickly is falling out of favor. Furthermore, shortly after the start of enrollment, NCCN guidelines adopted the stance that conventional imaging was no longer required in the setting of PSMA PET/CT imaging, solidifying the transition away from conventional imaging. Thus, the protocol is being amended to remove the requirement for conventional imaging as part of workup for oligorecurrence. In addition, to be generalizable, the study is designed to integrate future PSMA radiotracers that are incorporated into practice as well as changes in SST regimens over the time of the study.

All in the Marrow - a Case of Primary Bone Marrow Oedema

Introduction/Background: Primary bone marrow oedema syndrome is an elusive and less well-defined entity. Whether Rheumatologists should consider it as a stand alone diagnosis, is debatable. It possibly would be best described as an MRI feature which could be a finding in a number of diseases which would include the initial phases of Osteonecrosis of the bone, Rheumatoid Arthritis, Spondyloarthritis, Enthesitis related, Post traumatic, OA, Infections and Cancers. The treatment options become constricted due to the paucity of evidence. Rheumatologists need to consider this as an area of unmet need with development of consensus classification criteria and treatment approaches. Description/Method: 27-year-old male, Height 174 cms Weight 90 Kgs BMI 29 Kg/m2, became symptomatic in Jan 2022 with complains of pain in the both hip joints & groin regions, pain became excruciating and he became bed-bound, with early morning stiffness lasting approximately 45 mins. Had received steroids for COVID infection in August 2020. Investigations Hb 13.5gm/dl TLC 7000/mm3 Platelet 400 x 103/mm3 Sr Bil 0.8mg/dl AST 16 IU/L. ALT 24 IU/L Sr Creatininine 1.1mg/dl Blood Sugar Levels, Fasting 89 mg/dl Post Prandial 102 mg/dl ESR 10mm in 1st hour by Wintrobes method CRP Quantitative 29.38mg/L HLA B27 by PCR Negative, RF Negative, ACCP Negative Serum, IgG, Beta2 Glycoprotein 1.44 SGU Serum, IgM, Beta2 Glycoprotein 3.44 SGU Serum, IgG, Cardiolipin antibody 8.4 GPL Serum, IgG, Cardiolipin antibody 17.45 GPL Lupus anticoagulant by DRVVT Negative Sr Cholesterol 211mg/dl HDL 29 mg/dl LDL 156mg/dl TGs 130 mg/dl MRI Hips & SI joints Transient bone marrow oedema/osteopenia of bilateral hip. PET CT Increased metabolic activity in both hip joints Bone Scan (99mTcMDP) Increased vascularity in perfusion phase, increased accumulation in soft tissue in blood pool phase and increased uptake in bilateral Hip joints in skeletal phase scan, suggestive of CRPS Type-I. Management Was initially managed with Tab Etoricoxib 90mg BD, also started on Tab Sulphaslazine and Tab Methotrexate. However, when he had no symptomatic relief he was administered Inj Infliximab on 12 May 2022 and a second dose on 9 June 2022. He had excellent pain relief after the 1st dose, however after 10 days of the administration, he again began experiencing pain especially after walking. He also had pain in the knees on this occasion. He was also administered Inj Zoledronic 4mg on 23 May 2022. He is at present not requiring any NSAIDs over the last 1 month. Discussion/Results: The patient having presented with excruciating and debilitating pain was worked up and evaluation revealed features of bone marrow oedema on MRI which was corroborated with bone scan and PET CT imaging. The acute phase reactant CRP was also significantly elevated. The patient also gave history of early morning stiffness lasting approximately 45 mins. Hence an underlying Inflammatory process such as Spondyloarthritis(Peripheral) with enthesitis was considered. The confounding factors were the pain which worsened on mobilization, HLA B27 negative status, Rheumatoid Factor and ACCP negative status and past history of having received IV Corticosteroids for COVID infection in August 2020. In view of the debilitating pain and aworking diagnosis of Spondyloarthritis, hewas started onNSAIDs alongwith rest, initially, followed by conventional synthetic disease modifying agents in Rheumatic disease followed by biologic synthetic diseasemodifying agent - Inj Infliximab. The thought process was to avoid prolonged NSAID use to prevent the associated side effects. However, since Avascular Necrosis of the Femoral head is a very likely possibility, the patient is planned to be kept under close follow up. Key learning points/Conclusion: Collaborative efforts between the Departments of Nuclear Medicine, Radiology, Orthopaedics and Rheumatology are crucial in the early detection and approach to cases of Bone Marrow oedema. Avascular necrosis of head of Femur is a far more common entity and must be kept in ind even when a diagnosis of Bone Marrow oedema syndrome is being entertained. Diagnosis of Bone Marrow oedema syndrome must be entertained only as a diagnosis of exclusion. Continued follow up and regular imaging must be pursued rigorously in patients diagnosed with Bone Marrow oedema syndromes. There is a requirement to document acute phase reactants such as CRP and ESR in patients diagnosed with Avascular necrosis of bone as this data could help us differentiate AVN from Primary Bone marrow oedema in the early stages.

Did the COVID-19 pandemic influence the early diagnosis of bone metastatic disease? Experience in our health area

Aim/Introduction: To analyze the relationship (negative correlation) between the health care delay related with the Covid-19 pandemic and the cases detected of bone scans with multiple bone metastases coinciding with the oncological diagnosis. Material(s) and Method(s): 5849 full-body bone scans with 99mTc-HMDP performed during the periods of March 2018 -February 2020 (2910 cases) and March 2020 -February 2022 (2939 cases), which were evaluated as tumor extension studies. The official commence of the Covid-19 pandemic in Spain (March 2020) was chosen as the temporary time dividing line.In each period, the number of bone scans that presented multiple bone metastases was assessed, and the demographic and clinical characteristics of the patients were compared, searching for statistically significant differences. Result(s): In the pre-Covid19 period, 62 patients (2.13%) with multiple bone metastases were detected (average age 69.7 years;58% men). The tumors with the highest frequency of these findings were prostate cancer (38.8%) and breast cancer (27.4%).In the Covid-19 pandemic period, 70 patients (2.38%) had multiple bone metastases (average age 68.3 years;77.1% men). Prostate cancer was the tumor with the highest frequency of multiple bone metastases (55.7%).The findings have not shown a significant increase in the incidence of bone metastatic disease between these two periods (p=0.259);although, there are statistically significant differences regarding the characteristics of patients with multiple bone metastases at diagnosis, detecting in the pandemic period a higher number of cases in men (p=0.0088) and in patients with prostate cancer (p=0.0237). Conclusion(s): The health care delay caused by the pandemic has not been associated with a significant increase in the number of cancer patients with multiple bone metastases at diagnosis;although, in our health area, early diagnosis for male with cancer does seem to have been delayed, especially in those with prostate cancer.

Myocardial perfusion imaging findings of patients with history of COVID-19 infection: a single-center one-year experience

Aim/Introduction: COVID-19 pandemic has introduced significant new challenges in everyday medical practice, as history of COVID-19 infection becomes increasingly prevalent and its potential long-term effects and interactions with other known or unknown health problems have not been fully clarified. Here, we aimed to characterize patients with a history of COVID-19 infection who underwent myocardial perfusion imaging at the department of nuclear medicine of a tertiary cardiovascular medicine center. Material(s) and Method(s): Records of all patients with a history of COVID-19 infection with/without need for hospitalization who underwent scintigraphy from April, 1, 2021 to March, 31, 2022 at our department were obtained. Patients undergoing scintigraphy for indications other than myocardial ischemia/viability detection (for example lung perfusion scans, bone scans) were excluded. Regarding myocardial perfusion studies, the presence of scar or ischemia was determined, together with basic hemodynamic parameters (blood pressure, systolic-SBP, diastolic-DBP, pulse-PP) and the respective changes from rest to maximal stress, according to stress test applied. Result(s): In total, 152 patients undergoing myocardial perfusion imaging reported previous COVID-19 infection. For 3 patients, data were incomplete, so the remaining 149 formed our study group (94 male, 55 female, age 67>10years, 5>4 months after COVID-19 infection). In 48 of them (32.2%), treadmill stress test according to Bruce protocol was applied. Another 60 received intravenous adenosine infusion (40.3%), the remaining 41 undergoing regadenoson test (27.5%). Patient age differed significantly according to stress test type (treadmill: 63>10 years, adenosine 70>8 years, regadenoson: 66>10 years, p=0.0001). Forty five patients (30.2%) had reversible perfusion defects compatible with ischemia, while 21 (14.1%) showed permanent perfusion defects (myocardial scar). Both ischemia and scar were more common among patients who needed hospitalization due to COVID-19 compared to those with milder symptoms (ischemia: 17/40 among patients with history of hospitalization, 28/109 among those with no hospitalization due to COVID-19, p=0.048;scar: 11/40 among patients with history of hospitalization, 10/109 among those with no hospitalization, p=0.004). Among those undergoing treadmill test, the ones with history of COVID-19 hospitalization showed higher SBP and PP increase during exercise (86>17 versus 60>24mmHg for SBP, 65>18 versus 45>24mmHg for PP, p=0.009 and p=0.048 respectively), while DBP differences were insignificant. Conclusion(s): Abnormal myocardial perfusion findings in the form of both fixed and reversible perfusion defects are more common among patients needing hospitalization for COVID-19 infection. Altered hemodynamic response to exercise is also present in this patient population.

A Case of Bilateral Sequential Optic Neuropathies With Pachymeningitis and Aortitis: Difficulty in Differentiating Erdheim-Chester Disease From IgG4-Related Disease

Objective We describe a case of bilateral sequential optic neuropathies with pachymeningitis and aortitis, with findings that raised suspicion of Erdheim-Chester disease versus IgG-4 related disease. Background Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm characterized by tissue infiltration by foamy histiocytes, and chronic, uncontrolled inflammation. IgG4-related disease (IgG4-RD) is an insidiously progressive immune-mediated fibrotic disease typified by tumour-likemass formation in many affected organs. Neurologic manifestations are diverse. Design/Methods A 58-year-old male was transferred to our centre for acute onset sequential optic neuropathies. His visual acuity was light perception for the right eye and 20/50 in the left eye. Results Enhanced MRI of the brain and orbits showed focal pachymeningeal thickening and enhancement in the anterior cranial fossa and over the left frontal lobe with eccentric enhancement of the right optic nerve sheath. CRP was elevated (23 mmol/L to 62 mmol/L);extensive CSF and serum infectious and inflammatory investigations were unrevealing. PET body demonstrated aortitis and CT angiography suggested coronary artery vasculitis. Bone scan showed symmetric involvement of the long bones. Dural biopsy was delayed due to the Covid-19 pandemic and was completed following a protracted steroid course and a 15 mg/kg dose of cyclophosphamide. Pathology showed mixed inflammatory infiltrate and increased expression of IgG4 neutrophils.Clusters ofCD68+,CD1a, and S100-negative macrophages were seen in all layers of dura. No BRAF mutation was identified. Conclusions This case demonstrates classic imaging findings of ECD including pachymeningitis, symmetric long bone involvement and aortitis. Pathology in ECD may show characteristic foamy histiocytes, that were absent in this case. This case demonstrates the challenge of biopsy interpretation following immunosuppressive and cytotoxic therapy and the difficulty of differentiating ECD from IgG4-RD.

An unusual recurrent case of Cryptococcal sacroilitis in an immunocompetent elderly female in Rajasthan, India

Background: Cryptococcus lives in the environment all over the globe. Although it spreads via inhalation route still most of the exposed individuals never get sick as the majority of cases are seen in immunocompromised. Objective of this clinical case report is to highlight the rare fungal etiology associated with iliac bone abscess to avoid incorrect diagnosis and prompt management of case. Case Presentation: A 70-year-old elderly female presented with hip pain for a month duration, not relieved with analgesics in September, 2021. In MRI a well-defined irregularly marginated hyperintense focal lesion was found in left iliac bone with joint effusion suggestive of infective etiology, tubercular, or less likely metastasis. CT-guided biopsy reported occasional hyphae-like fragments giving an impression of acute on chronic osteomyelitis with suspicion of fungalinfection.Culture reported Cryptococcus ne oformans.Fungal markers and Beta-dglucan were indeterminate and Galactomannan was found negative for the sample. Extrapulmonary TB was ruled out by AFB staining, MGIT Culture, and GeneXpert MTB. Bone scan, tumor markers, and PET scan ruled out osteolytic lesion secondary to metastasis. Though PET Scan and HRCT thorax confirm pulmonary involvement giving a picture of bilateral interstitial lung disease along with multiple enlarged lymph nodes. Patient serum was found negative for HIV, HBV, and HCV. Liver and renal function tests were within normal range and in hematology, ESR was raised (50;normal range:0-20). Patient is hypertensive with HbA1c of 5.3. There was no history of travel, avian exposure, weight loss, and COVID-19 infection. Patient was started on voriconazole and considering generalized lymphadenopathy, a therapeutic trial of anti-tubercular therapy was started which was stopped within a week on patient non-compliance. Abscess resolved with voriconazole and patient was discharged. In February 2022, Patient presented with similar complaints. CT scan of this fluctuant nodule depicted hypoechoic lesion which was ultrasound-guided drained.Sections show many rounds of oval fungal organism which were found PASpositive with mucicarmine and alcian blue positive capsule.Budding yeast cells were seen on KOH mount and India ink preparation demon-strated capsule which was confirmed by Cryptococcal Antigen test giving an overall impression in favor of Cryptococcosis. Patient was started on oral fluconazole and Injection liposomal amphotericin B 250 mg for 14 days. Discussion and Conclusion(s): This is the first case of skeletal Cryptococcosis at our institution which was managed by antifungals without surgical debridement resulting in resolution of abscess. Isolated focal iliac bone cryptococcosis is unusual but may occur in immunocompetent with everyday exposure to the organism. Herein, Patient had bilateral lung involvement along with multiple lymphadenopathies with no evidence of TB bacilli which inferences that the isolate most likely originated from environmental bird droppings and has disseminated from pulmonary lesion to the iliac bone. The radiological findings of iliac cryptococcosis abscess were nonspecific.A definitive diagnosis was made on histopathological and fungal examinations of ultrasound-guided drained abscess. Patient will be followed in the near future for relapse or any other medical issues related to the case.

A Case of Shoulder Heterotopic Ossification Post COVID-19: Early Rehabilitation Considerations

Case Diagnosis: A case of a patient diagnosed with HO on the shoulder after prolonged immobilization due to COVID-19. Case Description or Program Description: The patient is a 48-year-old female who contracted COVID- 19, complicated by acute hypoxic respiratory failure requiring mechanical ventilation and prone positioning for 6 weeks, dysphagia, tracheostomy, proximal weakness, and functional decline. She was transferred to an LTAC for ongoing care, and once weaned off mechanical ventilation and stabilized, was admitted to inpatient rehabilitation. Her therapies were limited by proximal weakness in all limbs, left foot drop, neuropathic pain, bilateral shoulder pain, with pronounced range of motion restrictions in the left shoulder. Shoulder X-ray series revealed prominent heterotopic ossification inferior to the left glenohumeral joint. Setting(s): Inpatient rehabilitation hospital Assessment/Results: She received indomethacin for 6 weeks and intravenous pamidronate. Therapies included range of motion and stretching exercises, alongside traditional therapy for proximal weakness. After treatment, she had notable improvements in pain, range of motion, performing overhead activities, transfers, and activities of daily living. Critical illness polyneuropathy was confirmed on electrodiagnostic testing. Discussion (relevance): Heterotopic ossification is a debilitating condition usually seen after traumatic brain injury, spinal cord injury, stroke, or burns. It is characterized by bone formation in soft tissues around joints and typically presents with debilitating pain and loss of range of motion with a bony end feel. Plain radiographs fail to visualize HO in the early stage ( < 6 weeks) as bone is not yet ossified, requiring triple phase nuclear bone scan to detect. In some cases, surgical excision to prevent or treat contracture is unavoidable, but prone to bleeding and recurrence. Conclusion(s): This case, and a few recent publications, demonstrate this unusual sequela of COVID-19. Early identification and treatment can reduce severity and improve functional outcomes.

MULTIFOCAL BONE INFARCT AS A LATE SIDE EFFECT OF STEROID IN A PATIENT WITH BILATERAL LUNG TRANSPLANTATION SECONDARY TO COVID-19 PNEUMONIA/ARDS

CASE: A 37-year-old Hispanic female was referred to a tertiary center nine months status-post lung transplant secondary to post-COVID ARDS for evaluation of constant, dull, aching, gradually progressive pain in her bilateral lower extremities that was insidious in onset. Lab work was notable for persistently elevated alkaline phosphatase. 12 months prior to this admission, the patient was admitted for COVID-19 pneumonia for a week of ongoing fever, shortness of breath, and chest discomfort. Her hospital course was complicated by PE, ARDS, pneumothorax, required chest tube placement, intubation and ECMO. She was treated with dexamethasone, remdesivir, ceftriaxone, azithromycin, and convalescent plasma. Unfortunately, the patient developed post-ARDS pulmonary fibrosis and she was unable to wean off ECMO. Three months later, she underwent lung transplantation for postCOVID ARDS. Post- operative course was significant for profound shock intraoperatively, acute blood loss with delayed chest closure, Grade 3 primary graft dysfunction (PGD), critical illness myopathy, AKI with a need for continuous renal replacement therapy (CRRT) / hemodialysis, and Aspergillus pneumonia. She received two doses of COVID-19 vaccination. The patient underwent a bone scan that showed asymmetrically increased uptake in the bilateral femoral metadiaphysis, metaphysis, and proximal tibial metaphysis. There was questionable increased uptake in the humeral heads. MRI of the tibia showed bilateral distal tibial metaphysis/epiphysis heterogeneous T1 and T2 signal intensity lesions compatible with intramedullary infarct. There was no evidence of acute fracture or dislocation. Overall, the findings were consistent with multifocal osteonecrosis secondary to corticosteroid treatment. She is currently managed with analgesics in view of a nonsurgical approach as advised by the orthopedic team. IMPACT/DISCUSSION: Coronavirus disease 2019 (COVID-19) pandemic continues to present critical challenges for public health and medical communities globally. Its manifestations are predominantly respiratory, with multiorgan dysfunction in severe cases. Skeletal involvement is uncommon. Systemic corticosteroids such as dexamethasone are frequently used as the standard of care for critically ill COVID-19 patients to alleviate the hyperinflammatory response and reduce the need for mechanical ventilation. However, long-term treatment with dexamethasone can increase the risk of the development of osteonecrosis. In this case report, to our knowledge, we describe the first case of multifocal bone infarction in a patient treated with corticosteroids status-post lung transplant secondary to COVID-19 pneumonia. CONCLUSION: Recognizing clinical features of multifocal bone infarct as a late effect of corticosteroid treatment may be challenging given a complicated history of transplant and COVID-19. However, it may be prudent to consider osteonecrosis when a patient with prior steroid treatment history presents with musculoskeletal complaints.

Advantages of Positron Emission Tomography/Computed Tomography Over Conventional Computed Tomography in Evaluation of Lymphoma

Background: Lymphoma is one of the most common primary malignancies of the hematopoietic system. Lymphoid neoplasms are classified into Hodgkin’s and Non-Hodgkin’s lymphoma. Non-Hodgkin lymphoma accounts for about 5% of all cases of malignancies, It is less predictable than Hodgkin lymphoma and more liable for extra-nodal spread. Males are slightly more affected than females with higher incidence in white population. B-cell lymphomas have higher incidence in adults while T-cell lymphomas have higher incidence in children. With many imaging modalities that can describe the morphological changes in lymph nodes, it’s almost exclusive for the PET/CT to describe the biological changes in those lymph nodes through their uptake of FDG which has a great value in determining whether those lymph nodes are affected or not, which in turn will play an important role in treatment & management plan. What gives PET/CT scan the upper hand is that it acts on the biological level of the cells which permit early discovering of the affected lymph nodes, much earlier than standard C.T or MRI scan.

Neoadjuvant approach in patients with early breast cancer: evaluation of the breast cancer patient (patient assessment, staging, planning)

Neoadjuvant treatment (NAT) has become a standard treatment in locally advanced breast cancer and an option in early stage (stage I–II) breast cancer (EBC). It is known that patients who achieve a pathologic complete response (pCR) have better long-term out comes, especially Her2 positive and triple negative (TN) breast cancer. Selection of patients for NAT in early stage breast cancer rely in several factors, as patient characteristics (i.e., age and comorbid ities), tumor histology, stage at diagnosis and the potential changes in surgical or adjuvant treatments when NAT is administered. Early stage breast cancer patients that are not candidates for breast conservative surgery (BCS) at front, may benefit from NAT to reduce tumor size and facilitate surgery. In other cases, as young patients with TN tumors between 1–2 cm may benefit from NAT, even if BCS can be performed up front, as chemotherapy will be given anyway along the treatment and there is a high likelihood of pCR. Patients with a positive axilla at diagnosis, regardless of tumor size, may also benefit from less axillary surgery if axillary pCR is achieved. Rates of axillary pCR are especially high in TN and Her2 positive tumors. A distinct approach is suggested in luminal tumors subtypes. In these patients, besides the factors already mentioned, intensity of hormone receptor expression would help to decide on neoadjuvant hormone or chemotherapy treatment. Immunohistochemistry differentiation between luminal A and B by Ki67 assessment and in some cases, the use of genomic platforms may help defining type of NAT. Assessing breast cancer patients for NAT include incorporating all factors into the decision making process. In the COVID era, we have witnessed the use of NAT in patients who may be directed to surgery, unable to have it performed, as surgery has been reserved for emergency cases only. In this situation, it has been a great challenge managing breast cancer patients and tailoring individualized treatment decisions. Besides physical examination, breast imaging is performed to assess extent of disease and to determine BCS eligibility before NAT. Breast imaging should include mammogram with tomosynthesis, breast and axillary US and in most of cases MRI. MRI may be omitted in S12 Speakers’ s / The Breast 56S1 (2021) S1–S16 selected cases (i.e. fatty breasts, neoadjuvant hormone therapy). Contrast enhanced mammogram is an emerging technique, whether it will add accuracy to the MRI findings or replace it in selected cases is still to be defined. Shear wave elastography is under investigation for assessment of response to neoadjuvant therapy as well as for predicting response. Generally, in EBC no further body imaging (CT or bone scan) is needed unless metastatic disease is suspected. PET scan is reserved for patients with inconclusive metastatic dissemination or with more advanced disease. Pathology confirmation by core biopsy and evaluation of estrogen and progesterone receptor, Her2, and Ki67 must be obtained before treatment. Axillary US will characterize axillary lymph nodes and will guide biopsy of axillary nodes. If planning NAT, markers need to be placed in breast tumor/s and in biopsy proven positive axillary node. Same breast imaging should be repeated after NAT to assess response and to determine type of breast and axillary surgery. Sentinel lymph node biopsy after NAT is the preferred method. After NAT, surgical plan is delineated taking into account baseline characteristics, tumor response and patient desire. Conflict of Interest: Honoraria: Agendia. Advisory Board: Sirius medical.

A CASE OF ERDHEIM-CHESTER DISEASE IDENTIFIED SIX MONTHS AFTER LUNG TRANSPLANT

TYPE: Case Report TOPIC: Transplantation INTRODUCTION: Erdheim-Chester disease is a rare type of non-Langerhans histiocytosis that can manifest with bone pain, marked elevation of alkaline phosphatase, and osteosclerotic lesions of long bones. CASE PRESENTATION: A 37-year-old female, bilateral lung transplant recipient (10/2020) with a history of post-COVID-19 acute respiratory distress syndrome, complicated by acute cellular rejection, antibody-mediated rejection, and refractory gastroparesis, was found to have Erdheim-Chester disease in the work-up of infiltrative pattern of liver enzymes at 6-months after transplant. DISCUSSION: The early postoperative course was complicated as described above;during her most recent hospital admission, she had an isolated elevation of alkaline phosphatase (208 U/L) with no obvious gastrointestinal symptoms, excluding gastroesophageal reflux or other hepatobiliary pathology. Over the course of one week, her alkaline phosphatase increased to 928 U/L, and the patient described a new onset, mild and non-specific lower tibial pain. A gamma-glutamyl transferase was elevated, necessitating a skeletal work-up. A bone scan and lower extremity radiographs both showed subtle, patchy, intramedullary sclerosis and cortical thickening in the right lower extremity. Together, her bone pain, elevated alkaline phosphatase, and radiologic features were consistent with Erdheim-Chester disease. Although a bone biopsy was warranted, given her guarded prognosis, this intervention was not pursued. CONCLUSIONS: Erdheim-Chester disease generally requires careful observation for disease progression. Unfortunately, in a lung transplant recipient with worsening allograft function and repeated hospitalization, the prognosis is poor. DISCLOSURE: Nothing to declare. KEYWORD: Erdheim-Chester Disease