PET Scan Results Research Articles

5051 Clinical Correlation between TSH levels and TAU Imaging

Abstract Disclosure: S. Sunil: None. Background: Tau-PET Scan measures brain tau deposition. TSH levels related to cognitive impairment. We analyzed the correlation of TSH levels to tau-PET imaging in a memory clinic. Hypothesis: Tau-PET positivity correlates with lower TSH values in the clinic patients. Objectives: To assess the correlation of tau-PET positivity to TSH levels in memory clinic patients. Method: Retrospective observational chart review study of patients attending a memory clinic in Boston, MA, with TSH levels and tau-PET scan included for analysis. No stratification based on initial or final diagnosis, severity of cognitive impairment, or tracer used. Baseline TSH levels and a binary PET scan result were analyzed with covariates age, sex and race. Analysis done on ‘R’ v. 2.4.0. Pearson correlation estimated TSH levels to tau-PET status. Kruskal Wallis/Chi square tests for relationship of age, sex, gender and education with TSH levels and tau-PET status. ROC analyses and sensitivity/specificity were obtained. Results: Tau PET positivity did not correlate significantly with TSH levels (r= 0.0655, 95%CI -0.388 to 0.494, p=0.78). Conclusion: Tau PET does not correlate with TSH levels, possibly due to a ceiling effect in the mild impairment subjects. Presentation: 6/2/2024

Comparative effectiveness of 6x R-CHOP21 versus 6x R-CHOP21 + 2 R for patients with advanced-stage diffuse large B-cell lymphoma

First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice. Utilizing the Netherlands Cancer Registry, we identified 1577 adult patients diagnosed with advanced-stage DLBCL between 2014–2018 who completed either 6x R-CHOP21 (43%) or 6x R-CHOP21 + 2 R (57%). We used propensity scores to assess differences in event-free survival (EFS) and overall survival (OS). At five years, EFS (hazard ratio of 6x R-CHOP21 + 2 R versus 6x R-CHOP21 [HR] = 0.89; 95% confidence interval [CI], 0.72–1.09) and OS (HR = 0.93; 95% CI, 0.73–1.18) were not significantly different between both regimens. In exploratory risk-stratified analysis according to the International Prognostic Index (IPI), high-IPI patients (i.e., scores of 4-5) benefit most from 6x R-CHOP21 + 2 R (5-year absolute risk difference of EFS = 16.8%; 95% CI, −0.4%−34.1% and OS = 12.1%; 95% CI, −5.4–29.6%). Collectively, this analysis reveals no significant differences on average in EFS and OS between the two treatments. However, the potential benefits for high-risk patients treated with 6x R-CHOP21 + 2 R underscore the need for future research.

Lymphocytic Variant of Triple-Negative Breast Cancer Carcinoma Erysipeloides: A Rare Case of Carcinoma Erysipeloides Following TNBC Mastectomy

Background: Carcinoma erysipeloides (CE) is a rare but significant cutaneous manifestation of metastatic breast cancer, often misdiagnosed due to its rarity and nonspecific presentation. This is particularly true in patients with triple-negative breast cancer (TNBC), where the disease may progress undetected by conventional imaging modalities. This manuscript aims to elucidate the challenges and implications of diagnosing CE in breast cancer survivors, emphasizing the insufficiency of PET scans in detecting such cutaneous metastases and the potential for mismanagement due to diagnostic oversight. Case Presentation: We present a detailed case study of a 43-year-old female with a history of metastatic TNBC, who developed suspicious skin lesions post-treatment. Despite initial negative PET scan results, further investigations revealed CE through histopathological examination of skin biopsies. The case highlights the critical need for biopsy in the presence of new skin lesions in breast cancer survivors, irrespective of imaging results. It also underscores the possibility of lymphatic spread of CE, which could lead to life-threatening complications if not properly managed. Conclusion: The diagnosis of carcinoma erysipeloides must be considered in patients with breast cancer presenting with unusual skin lesions. Increased vigilance and dermatological assessment should be integral to the post-cancer follow-up regimen. The findings advocate for revising current treatment protocols and guidelines to better manage and potentially prevent the complications associated with this diagnosis. Enhanced surveillance for dermatological changes and a more aggressive approach to the biopsy of new skin lesions in cancer patients are recommended to improve outcomes and prevent the misdiagnosis of CE.

“There has to be more caring”: patient and care partner experiences of the disclosure of amyloid-β PET scan results

Objectives To explore patient and care partner experiences of receiving an amyloid scan result, with a focus on how clinician disclosure practices influenced patient and care partner emotional responses to the scan result and/or diagnosis. Methods Semi-structured interviews with 38 people with mild cognitive impairment or dementia and 62 care partners who experienced the disclosure of results from an amyloid PET scan as part of the CARE-IDEAS study. We used thematic analysis to analyze interview transcripts. Results We identified four aspects of the disclosure process that could influence patient and care partner emotional experiences of the scan result/diagnosis: (1) mode of delivery, (2) presence of a care partner, (3) clarity of the scan result explanation, and (4) discussion of post-scan treatment and support options. Conclusions Emotional experiences of an amyloid scan result can vary depending on how results are communicated. These findings support previous efforts to develop standard disclosure protocols. Scan results should be delivered in person with the care partner present. Clinicians should give a clear explanation of the result and its implications in an empathetic manner. Options for treatment and support should be discussed for all patients.

Sarcoidosis as a cause of chronic back pain: a case report.

While sarcoidosis is typically a multisystem disease, it can, in some instances, exclusively affect the vertebrae, leading to back pain. Additionally, sarcoidosis may manifest with inflammation of the sacroiliac joints, not meeting the criteria for spondyloarthritis, yet contributing to back pain. In this report, we present a case involving a previously healthy 55-year-old woman who sought medical attention due to chronic back pain. She was subsequently diagnosed with spinal sarcoidosis, based on MRI, PET scan, and biopsy results. Furthermore, treatment with prednisolone monotherapy demonstrated substantial improvement in her symptoms.

CLINICAL CORRELATION OF MOCA AND TAU IMAGING

Abstract Background Tau-PET Scan measures brain tau deposition. Montreal Cognitive Assessment (MOCA) is used for cognitive impairment in (MCI) and Alzheimer Disease (AD). We analyzed the correlation of MOCA to tau-PET imaging in a memory clinic. Hypothesis Tau-PET positivity correlates with lower MOCA scores in memory clinic patients Objectives To assess the correlation of tau-PET positivity to MOCA test scores in memory clinic patients To evaluate an MOCA score cut-off that translates optimally to tau-PET positivity Method Retrospective observational chart review study of 34 patients attending a memory clinic in Boston, MA, with MOCA score and tau-PET scan included for analysis No stratification based on initial or final diagnosis, severity of cognitive impairment, or tracer used. Baseline MOCA and a binary PET scan result were analyzed with covariates age, sex and race. Analysis done on ‘R’ v. 2.4.0. Pearson correlation estimated MOCA score to tau-PET status. Kruskal Wallis/Chi square tests for relationship of age, sex, gender and education with MOCA score and tau-PET status. ROC analyses and sensitivity/specificity were obtained. Results Tau PET positivity did not correlate significantly with MOCA score (r= -0.24, 95%CI –0.54 to -0.12, p=0.19). A cut point of 22 on the MOCA estimated tau deposition in the brain by PET scan, with an AUC of 80%, 95% CI –0.6 to –0.99, possibly indicating a ceiling effect on the MOCA. Conclusion Tau PET does not correlate with MOCA scores, possibly due to a ceiling effect in the mild impairment subjects.

Association between results of an amyloid PET scan and healthcare utilization in individuals with cognitive impairment.

The Imaging Dementia Evidence for Amyloid Scanning (IDEAS) study reports that amyloid PET scans help providers diagnose and manage Alzheimer's disease and related dementias (ADRD). Using CARE-IDEAS, an IDEAS supplemental study, we examined the association between amyloid PET scan result (elevated or non-elevated amyloid), patient characteristics, and participant healthcare utilization. We linked respondents in CARE-IDEAS study to their Medicare fee-for-service records (n = 1333). We examined participants' cognitive impairment-related, outpatient, emergency department (ED), and inpatient encounters in the year before compared with the 2 years after the amyloid PET scan. Individuals with a non-elevated amyloid scan had more healthcare encounters throughout the overall study period than those with an elevated amyloid scan. Regardless of the amyloid scan result, cognitive impairment-related and outpatient encounters overall decreased, but ED and inpatient encounters increased in the 2 years after the scan compared with the year prior. There was minimal evidence of differences in healthcare utilization between participants with an elevated and non-elevated amyloid scan. There is no difference in change in healthcare utilization between people with scans showing elevated and non-elevated beta-amyloid.

Disclosure of Amyloid PET results to Cognitively Impaired and Unimpaired Participants Enrolled in Alzheimer’s Disease Research Studies

AbstractBackgroundPrior studies have demonstrated the safety of amyloid PET scan disclosure to research participants. However, existing research has been conducted in predominantly white, cognitively intact, and highly educated samples. The Wake Forest Alzheimer’s Disease Research Center (ADRC) implemented a protocol to provide amyloid PET disclosure to a diverse cohort of participants with and without cognitive impairment.MethodEligible participants who complete an amyloid PET scan at the Wake Forest ADRC may consent to receive amyloid PET scan results. Prior to consent, participants are informed of possible results (elevated/not elevated) and how these results are related to Alzheimer’s disease (AD) risk. The disclosure process involves three phases: 1) pre‐disclosure assessment of anxiety and depression, 2) feedback session with a trained clinician, and 3) post‐disclosure completion of the Impact of Events Scale (IES). Additionally, a qualitative survey was developed to collect participant feedback following the disclosure session.Results170 participants (CN = 103, MCI = 48, dementia = 17, other = 2) have received amyloid disclosure; age: 70.5 (7.9); education: 15.7 (2.7); 62% female; 87% white). There was a statistically significant difference in IES scores between CN/MCI participants (CN = 4.3(7.2), MCI = 8.6(10.7), t(165) = 2.8, p = 0.005). There was no significant difference between IES scores in other cognitive pairs (CN‐Dementia = t(165) = 1.5, p = 0.134, MCI‐Dementia = t(165) = 0.36, p = 0.729).Post‐disclosure feedback surveys were completed by 41 participants (age = 71.7 (6.7) years, education = 15.9 (2.4) years, 63% female, 83% white) who reported (1 = strongly disagree, 5 = strongly agree) that receiving their results was a positive (M = 4.6 (0.6)) and informative (M = 4.78 (0.47)) experience, and given what they now know, they would chose to receive their results again (M = 4.58 (0.87)). There were no significant differences in responses between cognitive groups. Participants also reported that knowledge of their PET results will impact their future thoughts, feelings, and behaviors (M = 4.00 (1.02)).ConclusionAmyloid disclosure is safe and well tolerated by a diverse cohort, though participants with MCI reported higher IES scores post‐disclosure. Participants reported positive experiences on a feedback questionnaire and would choose to receive results again.

Management and Outcomes for Primary Mediastinal B-Cell Lymphoma Patients with Partial Metabolic Response

Background: The optimal management of patients with primary mediastinal B-cell lymphoma (PMBCL) who experience a partial metabolic response (PMR) on FDG-PET after initial systemic therapy is unclear. This study aimed to investigate different management strategies and outcomes for PMBCL patients who achieved PMR following primary systemic therapy, utilizing a single-center retrospective design. Methods: We reviewed the electronic medical records of 121 PMBCL patients who underwent post-chemotherapy PET scans at the Princess Margaret Cancer Center, Toronto, from January 2009 to September 2021. Using Modified Lugano criteria (2014), post-chemotherapy PET scan results were evaluated, with Deauville score (DS) 0-3 considered a complete metabolic response. Demographic, clinical, and imaging characteristics of the PMBCL population were analyzed. The Kaplan-Meier method was used to estimate progression-free survival (PFS), measured from the time of the post-systemic therapy PET. Results: A total of 121 patients with PMBCL underwent post-chemotherapy PET scans. Among them, 49 patients (40%) demonstrated incomplete metabolic response (DS4-5) Among these 49 patients, 12 showed primary refractory disease, while 37 demonstrated a partial metabolic response (PMR, DS4). The median age at diagnosis of the 37 patients with PMR was 30.8 years (range:18.4 - 52.8 years), and 20 (54%) were female. The median length of follow-up for these patients was 3.7 years (range: 0.4 to 9.2 years). Most PMR patients were stage I/II (26 patients, 70.3%), while the remaining were stage III (2 patients, 5.4%), or stage IV (8 patients, 21.6%), and 26 (70.3%) had a large mediastinal mass (maximum diameter exceeding 10cm). Initial systemic treatment was R-CHOP-21 (34 patients, 91.9%), R-CHOP combined with dose-adjusted R-EPOCH (2 patients, 5.4%), and dose-adjusted EPOCH (1 patient, 2.7%). Thirty one patients (83.8%) received 6 cycles. Following treatment strategies were employed to manage PMR: 1) radiation therapy (RT) only with or without biopsy in 30 patients (80.1%); 2) an observational approach (repeating PET scans without immediate treatment) in 3 patients (8.1%); 3) salvage chemotherapy in 3 patients (8.1%) and other approach in 1(2.7%) patient. The 2-year progression-free survival (PFS) rate for all patients with incomplete metabolic response (n=49) was 74.5% (95% CI = 62.5% to 88.9%). For patients with primary progression on post-chemotherapy PET scans the 2-year PFS (ie free of 2nd progression) was 40% (18.7% to 85.5%), while the 2-year PFS for patients with PMR was 85.4% (74.3% to 98.1%). PMR patients who underwent radiotherapy (RT) had the 2-year PFS rate of 92.7% (95% CI: 83.5% to 100.0%). No progression or relapsed occurred among the 3 patients with PMR who were managed with repeating PET scans without immediate further treatment. Conclusion: This study replicates prior work demonstrating a higher rate of incomplete metabolic response for PMBCL patients following R-CHOP-21 than typically reported for DLBCL. RT to persistent PET-avid sites is associated with excellent PFS. The favorable outcome of PMR patients without any additional treatment illustrates the non-trivial risk of false-positive PET scans following systemic therapy, and the need to identify criteria that can distinguish those who need additional treatment from those who can be safely observed.

Visual reading for [18F]Florzolotau ([18F]APN-1607) tau PET imaging in clinical assessment of Alzheimer's disease.

Tau-targeted positron emission tomography (tau-PET) is a potential tool for the differential diagnosis of Alzheimer's disease (AD) and to clarify the distribution of tau deposition. In addition to the quantitative analysis of tau-PET scans, visual reading supports the assessment of tau loading for clinical diagnosis. This study aimed to propose a method for visually interpreting tau-PET using the [18F] Florzolotau tracer and investigate the performance and utility of the visual reading. A total number of 46 individuals with 12 cognitively unimpaired subjects (CU), 20 AD patients with mild cognitive impairment (AD-MCI), and 14 AD with dementia (AD-D) patients with both [18F]Florbetapir amyloid PET and [18F]Florzolotau tau PET scans were included. Clinical information, cognitive assessment, and amyloid PET scan results were recorded. For visual interpretation, a modified rainbow colormap was created and a regional tau uptake scoring system was proposed to evaluate the degree of tracer uptake and its spatial distribution within five cortical regions. Each region was scored on a scale of [0, 2] as compared to the background, and that resulted in a global scale range of [0, 10]. Four readers interpreted [18F]Florzolotau PET using the visual scale. The global and regional standardized uptake value ratios (SUVr) were also calculated for analysis. The result indicates the average global visual scores were 0 ± 0 in the CU group, 3.43 ± 3.35 in the AD-MCI group, and 6.31 ± 2.97 in the AD-D group (p < 0.001). The consensus among the four observers on image scores was high with an intraclass correlation coefficient of 0.880 (95% CI: 0.767-0.936). The average global visual score was significantly associated with global SUVr (r = 0.884, p < 0.0001) and with the CDR-sum of box (r = 0.677, p < 0.0001). The visual reading method generated a visual score of [18F]Florzolotau tau-PET with good sensitivity and specificity to identify AD-D or CU individuals from the other patients. The preliminary result also showed that the global visual scores are significantly and reliably correlated with global cortical SUVr, and associated well with the clinical diagnosis and cognitive performance.

Effect of Amyloid PET on Clinical Management of Alzheimer’s Disease Medication Therapy: The Khatib Study (P11-6.009)

<h3>Objective:</h3> Evaluate the role of amyloid-beta PET scans as a diagnostic tool in clinical settings and its influence on patient care management with respect to Alzheimer’s disease drug therapy. <h3>Background:</h3> The NIA-AA 2018 guidelines for clinical research define Alzheimer’s disease (AD) on a biological basis, requiring the presence of amyloid deposition in the brain. This framework helps to more precisely define the processes underlying cognitive impairment, and is particularly poignant given the advent of amyloid-beta PET scans which allow the visualization of amyloid-beta in vivo. It is unclear how this framework may lead to changes in management of patients, particularly in an ethnically and culturally diverse location such as in South Florida. <h3>Design/Methods:</h3> We included 102 cognitively impaired patients from the multi-site Khatib Study (mean age 77+/−7 years, 45% women, 15% Hispanic). Patients were evaluated for AD drug therapy (cholinesterase inhibitors and memantine) before and after amyloid-beta PET scan by neurologists. The probabilities of change in AD drug therapy by amyloid-beta PET scan results were estimated using Wilson intervals for binomial proportions and tested using the McNemar test. <h3>Results:</h3> For amyloid PET positive patients (n=68), the use of AD drug therapy increased significantly (<i>p</i>&lt;.05), from 78% (95%CI [67,86]) to 91% (95% CI [82,96]). A total of 15% (95%CI [8,25]) started AD drug therapy and 2% (95%CI [0.3,8]) stopped AD drug therapy. For amyloid PET negative patients (n=34), the use of AD drug therapy decreased significantly (<i>p</i>&lt;.05), from 76% (95%CI [60,88]) to 53% (95%CI [37,69]). A total of 29% (95%CI [17,46]) stopped AD drug therapy and 6% (95%CI [2,19]) started AD drug therapy. <h3>Conclusions:</h3> Clinical confirmation of patients’ amyloid PET status resulted in increases in prescribed AD drug therapy for amyloid positive patients and decreases in the amyloid negative patients. This study highlights the significant bidirectional influence of amyloid PET scans on patient care management. <b>Disclosure:</b> Ms. Ariko has nothing to disclose. Miss Modjeski has nothing to disclose. Dr. Chang has nothing to disclose. Ms. Merrifield has received personal compensation for serving as an employee of The Council on Aging of Martin County - The Kane Center. Ms. Ripper has received personal compensation for serving as an employee of the council on aging of Martin County Inc. Mrs. Clark Dowd has nothing to disclose. James Galvin has nothing to disclose. Dr. Camargo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Camargo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GE Health. The institution of Dr. Camargo has received research support from American Academy of Neurology.

EDEN (Etude Désescalade sEmiNome): Prospective therapeutic de-escalation and miRNA-M371 biomarker evaluation phase II study for stage IIa/IIb &lt; 3 cm seminomas.

TPS434 Background: At diagnosis, 10 to 15% of testicular pure seminomas have a stage II defined by the presence of retroperitoneal lymph node metastases. The optimal choice of treatment modalities are associated with excellent efficacy but also acute and late toxicities. De-escalating treatment for seminoma patients with stage IIb, IIc and III and good prognosis according to IGCCCG (International Germ Cell Cancer Collaborative Group) based on negative FDG-PET (Fluorodeoxyglucose Positron Emission Tomography) after 2 cycles of EP (etoposide, cisplatine) chemotherapy seems feasible and safe according to SEMITEP cohort 2 results (Loriot Y, and al GETUG SEMITEP Trial: Eur Urol. 2022 Aug;82(2):172-179). Serum levels of microRNA (miR)-371a-3p (miRNA-M371) have been significantly associated with clinical stage and response to treatment in testicular germ cell tumors, with sensitivity and specificity higher than those of classic markers. The aim of the study NCT05529251 is to propose a new therapeutic approach for the stages IIa/IIb. Methods: This phase II, multicenter, prospective, randomized, non-comparative, de-escalation study will include patient with primary testicular seminomatous germ cell tumor with stage IIa/IIb &lt; 3 cm in largest diameter seminoma, histologically proved after orchiectomy and good prognosis according to IGCCCG and LDH (Lactate DesHydogenase) &lt; 2.5 x Upper Limit of Normal (ULN). They must have progressive disease and no prior treatment with radiotherapy or chemotherapy. In case of negative week-3 (after 1 EP cycle) PET-scan, patients will be randomized according to 2 arms ARM A: Boost of radiotherapy 20 to 30 Gray (Gy); ARM B Carboplatin AUC7 chemotherapy. In case of positive week-3 PET-scan: 3 courses of EP chemotherapy (ARM C). Primary outcome will include progression-free rate at 36 months. Secondary Outcome Measures will be serum level of miRNA M371, correlation with response to treatments and PET scan results, overall survival (OS), quality of life and tolerance to treatment. Blood samples (miRNA-M371) will be collected at screening, at the time of randomization before second cycle of chemotherapy or radiotherapy, at the end of treatment and at relapse. Enrollment has started in October 2022. A total of 90 patients will be included in the interventional study, leading to approximately 60 patients with negative FDG-PET randomized. Clinical trial information: NCT05529251 .

Bio‐Hermes: A Validation Study to Assess a Meaningful Relationship Between Blood and Digital Biomarkers with Aβ PET Scans for Alzheimer’s Disease

AbstractBackgroundThe Global Alzheimer’s Platform Foundation® (GAP) has developed a biomarker study (Bio‐Hermes) that will compare results of blood and digital biomarker tests with the results of brain amyloid PET scans and traditional cognitive tests. The trial will enroll 1,000 participants across three cohorts: Healthy, MCI, and Mild AD. In addition, Bio‐Hermes has a discrete recruiting endpoint that requires enrollment of a minimum of 200 participants (20%) from traditionally underrepresented populations (Black/African American &amp; Latino). Bio‐Hermes will generate a unique, well‐characterized, diverse sample set that will explore the utility of several leading biomarkers. This study will contribute to reducing the time and variability of therapeutic clinical trials in Alzheimer’s disease. Bio‐Hermes will generate a first of its kind, “head‐to‐head” comparison of a broad set of AD biomarkers.Method1. GAP activated 13 sites based on high productivity, access to a large AD population, commitment to recruiting traditionally underrepresented populations, and proof of COVID‐appropriate processes and SOPs.2. 3 cohorts established:• Cohort 1 – Healthy• Cohort 2 – MCI verified• Cohort 3 – Mild AD verified3. Sites collect Aß 42/40, p‐Tau 181/217/231, NfL blood biomarkers, full gene sequencing, including APOE status, traditional cognitive tests, family history, medications, retinal scan, digital cognitive tests, and centrally read Aß PET scans.4. Novel and focused recruitment efforts deployed to prioritize diverse representation.ResultAs of 1/27/2022:1. 6% of enrollment goal achieved (686 out of 1,000)• Cohort 1: 371 enrolled out of 400, (21% Aß Positive)• Cohort 2: 244 enrolled out of 300, (34% Aß Positive)• Cohort 3: 71 enrolled out of 300, (55% Aß Positive)2. 19% from traditionally underrepresented populations3. Screen fail rate of 15.9%4. 208 participants enrolled in the Retispec Sub‐StudyConclusionBio‐Hermes provides a well‐characterized, highly useful dataset including one of the most diversified populations in an AD study, illustrating that traditionally underrepresented populations can be successfully recruited. This study facilitates the discovery of potential biomarkers when compared to Aß PET and validates their predictive value for assessment/screening purposes. Bio‐Hermes is establishing a subset of potential participants for downstream AD therapeutic trials that will significantly lower screen fail rates.

Longitudinal Qualitative Analysis of the Role and Perspective of the Care Partner During and Four Weeks Following Disclosure of Amyloid PET Scan Results

AbstractBackgroundAmyloid PET scans allow for the visualization of amyloid plaque in the brain, which, in the context of mild cognitive impairment (MCI), signal heightened risk for progression to Alzheimer’s dementia (AD). Disclosure of such results can profoundly impact patients as well as their family care partners. The purpose of this study was to examine the role and perspectives of family care partners during and after the return of amyloid PET results.MethodWe used qualitative description to analyze transcripts of audio‐recorded results disclosure sessions and 4‐week follow‐up interviews of participants with MCI and their care partners who were randomized to the disclosure arm of the Return of Amyloid Imaging Scan Results (RAISR) trial. Focusing on care partners (n = 36), we conducted line by line coding and thematic analysis with the goals of 1) categorizing the frequency and nature of the questions raised by care partners during the open‐ended segment of the disclosure sessions, and 2) describing care partners’ perceptions of their loved one’s results in the month following disclosure.ResultAt disclosure, 13 families received positive for amyloid, and 21 received negative scan results. Care partners of those learning of amyloid positivity asked approximately twice as many questions as those receiving negative results (averaging 5.6 vs. 2.8 questions per session). Seven themes were identified in the questions: study logistics, AD/AD care, result clarification, next steps given result, outside resources, requests for scan images, and “other.” The vast majority of questions fell under AD/AD care (n = 47), followed by questions about study logistics (n = 24). The overarching theme of the week 4 interviews was a general sense of acceptance of the scan results. However, instances of inadequate comprehension of the scans’ implications were noted, particularly among partners of amyloid negative patients, some of whom interpreted the result to mean that their loved one’s MCI was nonprogressive.ConclusionFamily care partners play active roles in eliciting information and clarification during amyloid PET results disclosure. However, our findings regarding care partners of amyloid negative patients affirm that disclosing clinicians should not assume that those who ask fewer questions have an adequate understanding of the information presented.

Immunoglobulin High Throughput Sequencing (Ig-HTS) Minimal Residual Disease (MRD) Analysis Is an Effective Surveillance Tool in Patients with Mantle Cell Lymphoma

Introduction Mantle cell lymphoma (MCL) accounts for 4-6% of B-cell non-Hodgkin lymphoma (NHL), with historically poor outcomes. With the advent of targeted and cellular therapies, responses and durable remissions have improved although cure remains elusive. As patients experience longer remissions, this raises the question of the optimal surveillance modality. For NHL in general, surveillance imaging surveillance does not improve outcomes and is associated with increased radiation exposure, high costs, and anxiety to patients. Peripheral blood minimal residual disease (MRD) analysis offers a potential alternative to surveillance imaging that is more sensitive, less costly, and eliminates the risk of radiation exposure. The clonoSEQ® assay (Adaptive Biotechnologies) is an FDA-cleared Ig-HTS MRD assay which takes advantage of the fact that B-cell lymphomas nearly always have one or more unique clonal immunoglobulin (Ig) gene rearrangements which can serve as a tumor "marker". These sequences can be detected in the peripheral blood, as circulating tumor DNA (ctDNA), with a sensitivity as low as 1 cell in 1,000,000. Starting in 2015, our group has monitored many of our MCL patients using the clonoSEQ® MRD assay. This has been done in lieu of surveillance imaging, or to minimize its use. We performed a retrospective analysis to summarize our experience with this assay to demonstrate its utility as a surveillance tool for MCL patients. Methods We conducted retrospective data collection and analysis of outcomes in patients who underwent first-line treatment for MCL and were then monitored post-treatment using the clonoSEQ® assay. We captured baseline patient characteristics, as well as every time a surveillance imaging or ctDNA (clonoSEQ®) test was performed. We used swimmer plots to display timelines for individual patients, indicating all ctDNA tests (positive or negative), CT or PET scan results, as well as documented clinical relapse. We used Kaplan-Meier curves to show progression-free survival and overall survival of the entire cohort. We compared ctDNA to radiographic surveillance in terms of ability to detect relapse. Results A total of 31 patients were included. The median age of patients was 59, and the majority had low- or intermediate-risk disease by MIPI score, with 58% having a proliferation index above 30%. The majority (81%) underwent high-dose cytarabine-based induction, 77% underwent autologous transplant in first remission, and 42% received rituximab maintenance (see Table 1). With a median follow up of 5.8 years, overall outcomes with this cohort were excellent, with 69% and 60% progression-free at 5 and 10 years, respectively, and 96% and 92% alive at 5 and 10 years, respectively. Among the 12 patients who ultimately sustained a radiographic relapse, peripheral blood became MRD-positive in 11 patients (92%). The first positive MRD test came with a lead time of between 0-24 months (median 70 days) prior to radiographic relapse. Only one patient had a negative MRD result while being found to have progressive disease on imaging. That patient had a single site of disease at the base of tongue which caused symptoms early, despite a very low overall disease burden. Among the 19 patients who have been in continuous clinical remission, 17 have remained MRD-negative. The other 2 had "molecular relapse” (MRD positive without radiographic relapse), which allowed for pre-emptive rituximab treatment, which converted them back to an MRD-negative state. Several patients were able to enjoy 2-4 year intervals without any surveillance imaging, while still getting reassurance every few months from the negative ctDNA test (see Figure 1). Conclusions Our data suggests that the clonoSEQ® MRD assay is an effective surveillance tool for MCL patients following first-line therapy. In our experience, this MRD assay was predictive of relapse prior to imaging in all but one patient. In addition, the assay allowed for minimization of surveillance imaging, and early detection of MRD allowed for pre-emptive rituximab therapy in select patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Advance directives among cognitively impaired persons who had an amyloid PET scan and their care partners: a mixed-methods study

BackgroundLittle research exists on the role of β-amyloid PET scans as part of Alzheimer’s diagnostic tests and documentation of end-of-life preferences for persons with cognitive impairment. The study objectives were to examine the association of amyloid PET scan results (elevated vs. not elevated amyloid levels) and diagnostic category (mild cognitive impairment vs. dementia) with the likelihood of having an advance directive (reported a median of 4.5 months post-scan); to explore perceptions of PET scan results and their influence on planning for the future among persons with cognitive impairment and their care partners.MethodsSequential, explanatory mixed-methods design using data from dyads in the CARE-IDEAS study: advance directives as a factor of diagnostic category and scan result using multivariable logistic regression models; thematic analysis of semi-structured interviews with persons with cognitive impairment and care partners to explore how scan results influenced documentation of future healthcare preferences. Participants included 1784 persons with cognitive impairment and care partners from the CARE-IDEAS study, and a subsample of 100 semi-structured telephone interviews.Results81.6% of dyads reported an advance directive. Non-Hispanic, White participants had higher rates of advance directives. There was no significant association between having an advance directive and scan results. Qualitative analysis provided insight into perceived urgency to have advance directives, evolving healthcare preferences, and the context of completing advance directives.ConclusionsAlthough amyloid PET scans prompted persons with cognitive impairment and care partners to consider progressive cognitive impairment as part of evolving healthcare preferences, we found substantial variability in the perceived urgency of documentation.

First-In-Human Pilot PET Immunoimaging Study of 64Cu-Anti-Carcinoembryonic Antigen Monoclonal Antibody (hT84.66-M5A) in Patients with Carcinoembryonic Antigen-Producing Cancers.

Background: PET imaging using radiolabeled immunoconstructs shows promise in cancer detection and in assessing tumor response to therapies. The authors report the first-in-human pilot study evaluating M5A, a humanized anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb), radiolabeled with 64Cu in patients with CEA-expressing malignancies. The purpose of this pilot study was to identify the preferred patient population for further evaluation of this agent in an expanded trial. Methods: Patients with CEA-expressing primary or metastatic cancer received 64Cu-DOTA-hT84.66-M5A with imaging performed at 1 and 2 days postinfusion. 64Cu-DOTA-hT84.66-M5A PET scan findings were correlated with CT, MRI, and/or FDG PET scans and with histopathologic findings from planned surgery or biopsy performed postscan. Results: Twenty patients received 64Cu-DOTA-hT84.66-M5A. Twelve patients demonstrated positive images, which were confirmed in 10 patients as tumor by standard-of-care (SOC) imaging, biopsy, or surgical findings. Four of the 8 patients with negative imaging were confirmed as true negative, with the remaining 4 patients having disease demonstrated by SOC imaging or surgery. All 5 patients with locally advanced rectal cancer underwent planned biopsy or surgery after 64Cu-DOTA-hT84.66-M5A imaging (4 patients imaged 6-8 weeks after completing neoadjuvant chemotherapy and radiation therapy) and demonstrated a high concordance between biopsy findings and 64Cu-DOTA-hT84.66-M5A PET scan results. Three patients demonstrated positive uptake at the primary site later confirmed by biopsy and at surgery as residual disease. Two patients with negative scans each demonstrated complete pathologic response. In 5 patients with medullary thyroid cancer, 64Cu-DOTA-hT84.66-M5A identified disease not seen on initial CT scans in 3 patients, later confirmed to be disease by subsequent surgery or MRI. Conclusions: 64Cu-DOTA-hT84.66-M5A demonstrates promise in tumor detection, particularly in patients with locally advanced rectal cancer and medullary thyroid cancer. A successor trial in locally advanced rectal cancer has been initiated to further evaluate this agent's ability to define tumor extent before and assess disease response after neoadjuvant chemotherapy and radiotherapy. clinical trial.gov (NCT02293954).

The Placebo Response in Double-Blind Randomised Trials Evaluating Regenerative Therapies for Parkinson's Disease: A Systematic Review and Meta-Analysis.

In the field of stem cell technologies, exciting advances are taking place leading to translational research to develop cell-based therapies which may replace dopamine releasing neurons lost in patients with Parkinson's disease (PD). A major influence on trial design has been the assumption that the use of sham operated comparator groups is required in the implementation of randomised double-blind trials to evaluate the placebo response and effects associated with the surgical implantation of cells. The aim of the present review is to identify the improvements in motor functioning and striatal dopamine release in patients with PD who have undergone sham surgery. Of the nine published trials, there was at the designated endpoints, a pooled average improvement of 4.3 units, with 95% confidence interval of 3.1 to 5.6 on the motor subscale of the Unified Parkinson's Disease Scale in the 'OFF' state. This effect size indicates a moderate degree of improvement in the motor functioning of the patients in the sham surgical arms of the trials. Four of the nine trials reported the results of 18F-Fluorodopa PET scans, indicating no improvements of dopaminergic nigrostriatal neurones following sham surgery. Therefore, while the initial randomised trials relying on the use of sham operated controls were justified on methodological grounds, we suggest that the analysis of the evidence generated by the completed and published trials indicates that placebo controlled trials are not necessary to advance and evaluate the safety and efficacy of emerging regenerative therapies for PD.

How knowledge of elevated amyloid impacts neuropsychological performance in cognitively normal older adults: Findings from the REVEAL SCAN Study

AbstractBackgroundAlzheimer’s disease (AD) prevention trials enroll cognitively unimpaired persons with AD biomarkers. The REVEAL‐SCAN trial tested whether knowledge of elevated amyloid affects these persons' cognitive test performance.MethodCognitively unimpaired adults age 65‐80 with a first degree relative with AD, intact cognitive and functional status, and no unstable psychiatric or medical conditions received an AD dementia risk estimate and random assigned to either learn their amyloid (18F‐amyvid) PET scan result (D+) or to learn it 6 months later (D‐). At 6 weeks and 6‐months post‐disclosure, participants completed the ADCS‐PACC battery, a composite of 4 measures: Free and Cued Selective Reminding Test (free portion only), Logical Memory IIa test, Digit‐Symbol Substitution test, and Mini Mental State Exam. Scores from each test are standardized to a common Z‐score metric and a composite score is calculated by summing these standardized Z‐scores. We hypothesized that follow‐up ADCS‐PACC scores would be lower among elevated (A+) disclosed participants (D+) than elevated (A+) nondisclosed (D‐) participants.Result315 participants were randomized (84 elevated (41 A+D+/43 A+D‐), 231 not elevated (118 A‐D+, 113 A‐D‐)). We report analyses comparing PACC scores between A+D+ and A+D‐. Table 1 shows no statistically significant between group differences in participant characteristics. Both before and after multiple imputation and dropping outliers that were &gt;2 SD from the mean, PACC scores did not differ between groups at baseline. Linear regression mixed‐effects with repeated measures model (MMRM) adjusted for baseline PACC scores and time point showed that estimated mean scores at 6‐week and 6‐month did not differ between A+/D+ and A+D‐ participants (Model 1: D+ estimated mean 0.35, 95% CI: ‐0.13 to 0.84, compared to D‐ estimated mean 0.84, 95% CI: 0.38 to 1.31). The effect of disclosure on follow‐up PACC scores remained non‐significant after additionally adjusting for gender, race, education, and completion of follow‐up testing during COVID (Model 2: D+ estimated mean ‐0.38, 95% CI: ‐1.10 to 0.33, compared to D‐ estimated mean 0.06, 95% CI ‐0.65 to 0.78).ConclusionKnowledge of elevated amyloid among cognitively unimpaired individuals does not change performance on measures of cognition. Inspection of the variance suggests a dampening of practice effect.

The Impact of the COVID-19 Pandemic on the Diagnosis and Management of Patients with Classical Hodgkin Lymphoma: A Single-Center Experience

Background: The coronavirus disease 2019 (COVID-19) pandemic has brought life to a standstill all over the world. Especially in Istanbul, the most populated city in Turkey, many hospitals served as pandemic hospitals and suspended the examination of patients who were not infected with COVID-19. On the other hand, in this period, lockdown was applied frequently to control the pandemic and to reduce the transmission. It is known that the delay in the diagnosis and treatment of cancer can sometimes be fatal. Initial treatment choice in classical Hodgkin lymphoma (cHL) patients is determined by various factors including the stage of the disease. Therefore, detection of the disease at an early stage has prognostic importance. Our aim was to compare the time from symptom onset to diagnosis and period between diagnosis and treatment initiation, as well as the distribution of stages and treatment responses in cHL patients diagnosed and treated during the COVID-19 pandemic and in the pre-pandemic period.Methods: Patients who were diagnosed within the 2 years before the pandemic (between March 2018 and March 2020) and in a 12-month period during the pandemic (between March 2020 and March 2021) were compared in terms of demographic data, disease related factors, time interval between symptom to diagnosis, and interim treatment response. Clinical data were obtained from manual and electronic medical records retrospectively. PET scans were performed at baseline, after two cycles of chemotherapy, and end of treatment (EOT). The Deauville five-point scale (5-PS) was used in the initial staging and assessment of treatment response. The 5-PS; a score of 1, 2, or 3 was considered negative. The 5-PS score 4 or 5 was positive.Results: This single-center study included 90 newly diagnosed cHL patients, with a median age of 33.5 years (range, 17 - 70 years) and a male predominance (53.3%). The most common presenting symptom was a lump in the neck (41.1%), and also, 61.1% (n=55) of the cases had at least one B symptom. Patient characteristics were summarized in Table 1. Age and sex distributions were similar in both groups. Also, the number of patients >60 years was comparable (p=0.868). The most common histopathological subtype in both groups was nodular sclerosis (47.7% vs. 48%). In the pre-pandemic period and during the pandemic, the percentages of patients with early unfavorable disease were 66.7% and 77.8%, respectively (p=0.526). Although the percentage of patients with advanced-stage disease was higher during the pandemic than that observed in the pre-pandemic period (64% vs. 53.8%), this difference did not reach statistical significance (p=0.384). The median interval between symptom onset to diagnosis was significantly longer during the pandemic than was observed within the pre-pandemic era (16 weeks vs. 8 weeks, p=0.042). The median durations between diagnosis and treatment initiation were similar in both groups (13 days vs. 15 days, p=0.253). The majority of patients in both groups received ABVD as first-line therapy, and IFRT was performed in some patients with early-stage cHL (Figure 1). Among all patients (n=90), 85% of the cases had negative interim PET scan results, and this percentage was similar for both patient groups (84.6% vs. 88%, p=0.999). In the pre-pandemic period, 80% of the patients had complete response at EOT, on the other hand, no comparison was performed between two groups regarding response level at EOT, since nearly half of patients (48%) treated during the pandemic were not evaluated for the EOT response at the time of the analysis.Discussion & Conclusion: In our cohort, the time interval between symptom onset to diagnosis was significantly prolonged during the pandemic. Most probably the patients were afraid of admitting to the hospital due to the fear of contagion, or patients might have experienced difficulties in applying to a health facility, and lastly maybe they had tolerable symptoms, which might all have roles in the diagnostic delay during the pandemic. Higher percentage of patients with advanced-stage disease during the pandemic might also be associated with this delay, however, fortunately, this difference did not translate into a significant difference regarding interim treatment response in both groups. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.