Negative PET Scan Research Articles

EPID-33. EPITHELOID SARCOMA IN A LONG-TERM SURVIVOR OF AN ATYPICAL TERATOID / RHABDOID TUMOR WITH RHABDOID TUMOR PREDISPOSITION SYNDROME

Abstract INTRODUCTION Rhabdoid tumor predisposition syndrome (RTPS) predisposes to a high risk of developing Rhabdoid tumors in Brain, kidney; and is defined by a germline mutation in SMARCB1 (rarely SMARCA4) gene. The most frequent pediatric tumor associated with RTPS is atypical teratoid/rhabdoid tumor (ATRT), commonly diagnosed in children < 3 years of age. Epitheloid Sarcoma (ES) is a rare soft tissue sarcoma, arising in any age group and histologically defined by loss of SMARCB1 in tumor cells. METHODS We describe a long- term survivor of ATRT with RTPS presenting 12 years later with ES. Data was collected from medical chart review. RESULTS Our patient was diagnosed with ATRT and RTPS (SMARCB1) at 6 months of age and treated with chemotherapy as per ACNS0333 at diagnosis; by chemotherapy / focal radiation at first relapse and with alisertib on second relapse. At 10yrs of age she presented with multiple firm, skin-colored dermal nodules in both her hands (palms and fingers). She was diagnosed to have palmar warts and treated with topical cantharidin with a waxing and waning course. Subsequently the hand lesions were diagnosed as granuloma annulare and followed up with no therapy. At 12 years of age, lesion in tip of the right thumb increased in size and a punch biopsy was done which revealed ES with IHC showing loss of SMARCB1 in tumor cells. Staging CT of the chest showed multiple bilateral (b/l) small (<1cm) axillary lymph nodes with a negative PET scan. Bilateral axillary lymph node biopsies were negative for ES. She underwent excision of all the hand lesions with negative margins with no further therapy. CONCLUSION Based on our case and single case report in literature, we hypothesize that ES is likely a primary malignancy of RTPS and should be included in the spectrum of malignancies of RTPS.

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.

Abstract PO5-21-01: Carcinoma en cuirasse- a rare, but striking, cutaneous manifestation of metastatic breast cancer

Abstract Introduction: Carcinoma en cuirasse is a rare cutaneous metastatic presentation most commonly arising from primary breast cancers, typically after mastectomy. It appears like cellulitis and later develops into thickened rough patches of skin and even nodules. Carcinoma en cuirasse holds a poor prognosis, and treatment is difficult. Chemotherapeutic agents are unable to reach the tumor cells necessary, and radiation is ineffective because of skin curvature. Case Presentation: We report a female in her 70s with prior history of left breast ductal carcinoma in situ status post-radiation and lumpectomy, who presented with skin thickening of the left breast and solid masses in bilateral breasts 10 years later. Biopsy showed invasive ductal carcinoma of left breast (estrogen receptor [ER]/progesterone receptor positive [PR], human epidermal growth factor receptor-2 [HER2] negative) and ductal carcinoma in situ of right breast (ER/PR positive). She underwent right breast lumpectomy; however, the left breast mastectomy was aborted due to worsening of her skin findings on preoperative examination. An excisional skin biopsy revealed poorly differentiated invasive ductal carcinoma involving the dermis, deep dermis and focally involving the epidermis. Her diagnosis changed to stage 4 breast cancer, specifically carcinoma en cuirasse. Systemic treatment was initiated with palbociclib and letrozole and subsequently, she underwent left breast mastectomy given an excellent response to initial therapy. Surgical biopsy interestingly was HER2 positive and therefore her regimen was changed to taxotere, trastuzumab and pertuzumab. She completed adjuvant treatment and has been on maintenance trastuzumab along with letrozole currently and is doing well 5 years later with negative PET scans. Discussion: Our case is unique due to diagnosis of carcinoma en cuirasse before mastectomy, change in HER2 receptor status during treatment and excellent response to therapy with ongoing response to date. We think that an early diagnosis as well as targeted treatment could be the possible reasons for prolonged survival of more than 5 years. Conclusion: Any unexplained skin findings in breast cancer patients should prompt consideration of carcinoma en cuirasse. With ongoing treatment advances, many newer therapy options are available for metastatic breast cancer. Based on our case, we think that patients with this disease can have better outcomes. Citation Format: Manasi Godbole, Kashmira Wani, Shereen Zia, Vrushali Dabak. Carcinoma en cuirasse- a rare, but striking, cutaneous manifestation of metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-21-01.

Significance of a positive tau PET scan with a negative amyloid PET scan.

The implications of positive tau positron emission tomography (T) with negative beta amyloid positron emission tomography (A) are not well understood. We investigated cognitive performance in participants who were T+ but A-. We evaluated 98 participants from the Mayo Clinic who were T+ and A-. Participants were matched 2:1 to A- and T- cognitively unimpaired (CU) controls. Cognitive test scores were compared between different groups. The A-T+ group demonstrated lower performance than the A-T- group on the Mini-Mental Status Exam (MMSE) (p<0.001), Wechsler Memory Scale-Revised Logical Memory I (p<0.001) and Logical Memory II (p<0.001), Auditory Verbal Learning Test (AVLT) delayed recall (p=0.004), category fluency (animals p=0.005; vegetables p=0.021), Trail Making Test A and B (p<0.001), and others. There were no significant differences in demographic features or apolipoprotein E (APOE) e4 genotype between CU A-T+ and CI A-T+. A-T+ participants show an association with lower cognitive performance.

Measurement of amyloid beta in nasal secretions as a potential biomarker for Alzheimer’s disease

AbstractBackgroundWe investigated the level of amyloid beta (Aβ) in nasal secretions of patients with Alzheimer’s disease using multichannel impedance analyzer (ToAD) and electrical‐immunosorbent assay (El‐ISA), and determined the predictive value of Aβ in nasal secretions for AD diagnosis.MethodNasal secretions were obtained from 84 participants with probable AD dementia (ADD), 83 with amnestic mild cognitive impairment (MCI), 22 with cognitive decline associated with other neurological disorders (OND), and 62 cognitively unimpaired (CU) participants. Aβ oligomers in nasal secretions were analyzed using ToAD / El‐ISA analytical systems. Capture antibodies in El‐ISA kits specifically capture Aβ oligomer in nasal secretion, and then detection probes for El‐ISA method bind with amyloid beta oligomer sequentially. Finally, unbound free detection probes in solution was electrochemically measured by ToAD analyzer for quantifying Aβ oligomers. Because this analytical method is based on the back‐titration, the change of electrical signal is inversely proportional with the concentration of detectable Aβ oligomers. Electrical signals finally expressed to Cantis AD Index (CAI, 0∼99) which normalized by standards for system calibration.ResultThe CAI was higher in the probable ADD group than in the CU group (p &lt; 0.05). The accuracy of the CAI was fair in separating into the probable ADD and CU groups (AUC of the ROC curve = 0.665, 95% CI = 0.572‐0.758, SE = 0.047, p = 0.001). The accuracy of the CAI was fair in separating into the participants with positive amyloid PET scan and those with negative amyloid PET scan (area under curve [AUC] of the receiver operating characteristic [ROC] curve = 0.697, 95% confidence interval [CI] = 0.629‐0.766, SE = 0.035, p &lt; 0.001). The CAI has a negative correlation with Mini‐Mental State Examination score and positive correlations with Clinical Dementia Rating scale‐Sum of Boxes and amyloid PET centiloid scale scores.ConclusionThese results demonstrate that the level of Aβ in nasal secretions increases in AD and the detection of Aβ in nasal secretions using ToAD / El‐ISA analytical systems may be possible in predicting ADD.

Significance of a positive tau pet scan with a negative amyloid pet scan

AbstractBackgroundThe implications of a positive tau (T) Positron Emission Tomography (PET) with a negative beta amyloid (A) PET are not well understood. We investigated cognitive performance in participants who were positive on tau PET but negative on beta amyloid PET.MethodWe evaluated 98 participants from the Mayo Clinic Study of Aging (MCSA) and the Mayo Clinic Alzheimer’s Disease Research Center (ADRC) who were positive for Flortaucipir (FTP) and negative for PiB PET. Participants were classified as A‐ and T+ based on Standardized Uptake Value Ratios (SUVr) of FTP and PiB PET scans, and were matched 2:1 to amyloid negative and tau negative cognitively unimpaired controls from the MCSA. Cognitive test scores were compared between the combined ADRC/MCSA group and MCSA only group. We also examined clinical diagnoses in our cohort. The most common were Alzheimer’s Disease, mild cognitive impairment (MCI), Dementia with Lewy Bodies (DLB) and Frontotemporal dementia (FTD) amongst others.ResultThere were no significant differences in demographic features or PiB SUVr between groups. There were significant differences in APOE genotype between groups. In the combined ADRC/MCSA group, 25% of A‐T‐ and 13% of A‐T+ were APOE e4 carriers (p = 0.016), and in the MCSA only group, 27% of A‐T‐and 10% of A‐T+ were APOE e4 carriers (p = 0.010). In the combined ADRC/MCSA group, the A‐T+ group demonstrated lower performance than the A‐T‐ group on the Mini Mental Status Exam (MMSE) (p&lt;0.001), Wechsler Memory Scale‐Revised Logical Memory I (p&lt;0.001) and Logical Memory II (p&lt;0.001), Auditory verbal Learning Test Delayed Recall (AVLT) (p = 0.004), Category fluency animals (p = 0.005), Category fluency vegetables (p = 0.021), Trailmaking test A (p&lt;0.001), Trail making test B (p&lt;0.001), Wechsler Adult Intelligence Scale‐IV (WAIS‐IV) (p = 0.002), and Unified Parkinson’s Disease Rating Scale part III (UPDRS III) (p = 0.003). In the MCSA only group, the A‐T+ group had lower scores on Logical Memory II (p = 0.022), AVLT delated recall (p = 0.04), and WAIS‐R block design (p = 0.035) compared to the A‐T‐group.ConclusionPositive tau PET in the absence of beta‐amyloid positivity is associated with lower cognitive performance.

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Truly Refractory Hodgkin Lymphoma Patients Is Highly Effective and Responses Are Mediated By NK Cells

Background In the relapsed/refractory Hodgkin Lymphoma (HL) setting (RHL), the achievement of complete remission (CR) is fundamental in order to proceed with allogeneic stem cell transplantation (HSCT) consolidation. Immune checkpoint inhibitors (CI) have demonstrated clinical activity in patients relapsing after ASCT, although only 20% CR rate is observed. In order to improve the efficacy of CI in RHL, we previously reported a salvage treatment based on early CI therapy following post-autologous stem cell transplantation (ASCT) with the reinfusion of unselected autologous lymphocytes infusions (ALI). The rationale of this approach is based on the achievement of a disease debulking through ASCT conditioning. Early administration of CI (nivolumab) is performed on a minimal disease burden, while reinfusions of ALI reduce post ASCT immune depression eliciting CI efficacy. Aims The aim of this study was to evaluate the efficacy of the procedure in terms of CR rates and overall survival (OS) after an extended follow up. Biological endpoint was to investigate the lymphocyte subpopulations involved in the mechanism of response and investigate the role of NK-cells mediating anti tumor responses in HL. Methods Patient were eligible to this study after failure to respond to first line treatment (i.e. positive PET2 or PET6 scan) and underwent autologous lymphocyte apheresis upon enrollment. All patients received conventional 2nd line chemo followed by 3rd line chemo-immunotherapy with Brentuximab-Vedotin (BV) in non-responding patients. Patient failing to achieve CR after BV were enrolled in the treatment arm and proceeded to ASCT + CI and ALI, whereas patients responding to 2nd- or 3rd treatment received ASCT followed by ALI alone, as a control cohort (figure 1A). NK cell degranulation assay was evaluated by staining for CD107a (LAMP-1) expression on healthy-donors derived NK cells exposed to HL cell lines (L428 and L250), in the presence or absence of monoclonal antibodies targeting inhibitory or activating receptors. Surface and intracellular staining was performed prior to flow cytometry and analysis was performed on the CD3-/CD56+ gated population. Results Twenty-one patients with RHL (median age 32 years; range 18-65) underwent lymphocyte apheresis after failure of 1st line chemo and then proceeded to salvage therapy. Thirteen patients failed to respond to 2nd and 3rd line therapy and thus received early post-transplant CI supported with four ALI. Eight patients responded to 2nd line chemo (n=6) or 3rd line BV (n=2) and received ASCT followed by ALI alone. No adverse events were recorded, specifically, no immune-related toxicity was observed. All patients receiving ALI + CI (treated patients) achieved negative PET scan CR. Eight of them received HSCT consolidation. One patient refusing HSCT after achieving CR in this study relapsed and responded to CI re treatment followed by HSCT. All patients in the treatment arm are alive and disease-free after a median follow-up of 32 months (95% CI 26.4-51.0). Median disease-free survival (DFS) was not reached in treatment arm (Fig 1B). Four of the patients in the control arm relapsed (50%). Three of them responded to 3rd line therapy and proceeded to HSCT. One patient achieved CR with conventional CI treatment but refused HSCT and the other relapsing patient died because of progressive lymphoma after failure to achieve CR with conventional single agent CI. Median DFS in the control arm was 22 months (Fig 1B). NK cells showed higher expansion and a faster maturation in the treatment arm, compared to the control arm (p&amp;lt;0.05). As expected, HL cells lines do not express HLA class I and II, but express activating NK cells receptors (aNKG2D, aNKp30, aNKp46, aDNAM-1). In vitro, the activation of each of those receptors was able to trigger NK cells degranulation. Similarly, PD-L1 and PD-L2 blockade on HL cell lines significantly increased NK cell degranulation (p&amp;lt;0.05). Taken together, those observations support the role of NK cells in this setting. Conclusions Our data show very high anti-tumor activity of ALI + CI for RHL, allowing most patients to proceed to HSCT. RHL patients in the treatment arm had an excellent outcome if compared to the control arm, which included patient who did respond to conventional treatment. Biological data suggests that this approach may accelerate NK cell development/maturation and suggest that NK cells may mediate response to CI in HL.

57 Clinical Utility of Neuropsychological Evaluation in the Differential Diagnosis Between Late-Onset Primary Progressive Aphasia Semantic Variant (PPA-SV) Versus Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE): A Case Report

Objective:Primary progressive aphasia semantic variant (PPA-SV) is an atypical dementia subtype on the frontotemporal dementia (FTD) spectrum. PPA-SV is clinically defined by naming and semantic deficits, with progressive language decline that generalizes to other domains over time. Typically, it presents as an early-onset dementia with TDP-43 pathology, but 33-46% of PPA-SV cases display initial onset after age 65 with potentially different clinical features. Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE), a more recently discovered neurodegenerative entity, is defined by an older age of onset, hippocampal sclerosis/atrophy, and TDP-43 pathology with a gradually progressive amnestic profile that expands to other cognitive deficits over time. The authors present a case report with overlapping features and suspected TDP-43 neuropathology ante-mortem for two reasons: first, to highlight the need for clinical criteria to formally diagnose LATE, and second, to address a gap in the literature on the possible clinical differences of late-onset PPA-SV.Participants and Methods:The authors present a case of a 78-year-old Indian bilingual man (English dominant) with 18 years of education, noncontributory medical history, and gradually progressive cognitive complaints reported over the past few years who was seen for outpatient neuropsychological evaluation. Prior workup was notable for negative amyloid PET scan, negative p-tau 217 blood test, and abnormal brain MRI revealing marked bilateral hippocampal atrophy with ex vacuo ventriculomegaly and minimal cerebrovascular disease. He scored 23/30 on prior MMSE, was diagnosed with amnestic MCI, prescribed Namenda and Exelon, and complained of minor memory and word-finding difficulties with reportedly intact IADLs and no signs of NPH.Results:Neuropsychological testing revealed a profound dysnomia (RBANS Naming raw score = 1/10), and he provided 0 words on two semantic fluency tasks but 15 words on letter fluency. Receptive vocabulary score was also impaired (PPVT-4, &lt;1st %). Memory performance also demonstrated rapid forgetting of information (RBANS List Recall raw = 0/10, Story Recall raw = 0/12) with no benefit to recognition cues (RBANS List Recognition raw = 12/20), but slightly better visual memory recall, albeit still impaired (RBANS Figure Recall raw = 4/20). Grooved pegboard scores were significantly worse with right-hand than left-hand. Irregular word reading (NAART = 16th %ile) was significantly below expectations and thought to reflect more of a surface dyslexia rather than a cultural confounder given that he has lived in the US for over 50 years and his occupational and educational history was completed in English.Conclusions:Results support the clinical utility of neuropsychological evaluation in the differential diagnosis to support a predominant clinical syndrome of PPA-SV despite overlapping features with LATE and suspected TDP-43 pathology. This case report highlights the diagnostic issue with the lack of literature describing the typical clinical progression or suggested diagnostic criteria of LATE. These findings also indicate that late-onset PPA-SV may include greater memory deficits earlier in the course, but this may also be a clinical masquerade that is more reflective of the extent of language deficits. Further research on late-onset manifestations of PPA-SV and LATE consensus clinical guidelines is advised.

Negative predictive value of PSMA PET scan for lymph node staging in patients undergoing robotic radical prostatectomy and pelvic lymph node dissection

To assess the negative predictive value of PSMA PET scan for lymph node staging in patients undergoing robotic radical prostatectomy and pelvic lymph node dissection. A retrospective analysis of patients who underwent robotic-assisted radical prostatectomy with pelvic lymph node dissection and had a preoperative negative PSMA PET scan for metastasis was performed. The documented pre-operative variables studied included age, BMI, PSA at diagnosis, Gleason score, and biopsy ISUP grades. Patients were categorised as low, intermediate and high risk according to the D Amico classification. The post-op variables included were number of lymph nodes harvested, number of positive nodes, positivity rate, size of the node metastasis, T staging and ISUP grading. The overall negative predictive value of PSMA PET scan was 71.6%. Further sub-classification according to risk stratification demonstrated a NPV of 58.02%, 92.7% and 90% for high, intermediate and low risk, respectively. Pelvic lymph node dissection cannot be excluded based on a negative preop PSMA PET/CT scan.

Clinical authorization of amyloid PET in France: Towards a more precise diagnosis of Alzheimer's disease

The recent clinical authorization of amyloid PET in France represents a crucial step for the nuclear medicine community involved in the diagnosis of Alzheimer's disease (AD). At the era of ATN (Amyloid, Tau, Neurodegeneration) biomarkers, amyloid PET fills a need in patients with an atypical or mixed clinical presentation, in particular young patients (<65 years old), when the lumbar puncture is contraindicated or not feasible for technical reasons. Importantly, a negative amyloid PET scan discards the diagnosis of AD. Furthermore, early phase imaging of amyloid PET allows to estimate the perfusion neuronal state, increasing the diagnostic value of such PET radiotracer. Its role could be further developed in routine care for the selection and monitoring of promising disease modifiers therapies.

PD10-02 USING THE NEGATIVE PREDICTIVE VALUE AND SUVMAX OF PSMA PET/CT FOR AVOIDING PELVIC LYMPH NODE DISSECTION WITH RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023PD10-02 USING THE NEGATIVE PREDICTIVE VALUE AND SUVMAX OF PSMA PET/CT FOR AVOIDING PELVIC LYMPH NODE DISSECTION WITH RADICAL PROSTATECTOMY Amandeep Arora, Archi Agarwal, Mahendra Pal, Ganesh Bakshi, Santosh Menon, Gujela Ajit, and Gagan Prakash Amandeep AroraAmandeep Arora More articles by this author , Archi AgarwalArchi Agarwal More articles by this author , Mahendra PalMahendra Pal More articles by this author , Ganesh BakshiGanesh Bakshi More articles by this author , Santosh MenonSantosh Menon More articles by this author , Gujela AjitGujela Ajit More articles by this author , and Gagan PrakashGagan Prakash More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003250.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The prostate-specific membrane antigen positron-emission-tomography (PSMA-PET) scan is increasingly being utilized for staging prostate cancer (PCa). Here, we sought to evaluate the accuracy of the PSMA-PET scan with the aim of identifying patients who could be spared a pelvic lymph node dissection (PLND) at the time of radical prostatectomy (RP) based on the results of the PSMA-PET scan. METHODS: We retrospectively reviewed records of patients who underwent a PSMA-PET scan followed by an RP with extended PLND (external iliac, obturator and common iliac nodes) at our tertiary cancer care centre from Aug 2015 - September 2022. Patients were classified as clinically node negative or positive (cN0 or cN+) based on the PSMA PET scan. The nodal status in the PSMA-PET scan was compared with the final histopathology of the PLND (pN0 or pN+). RESULTS: A total of 205 patients were included and were stratified as follows based on MRI and PSMA-PET scans: 6 (2.9%) low-risk, 49 (23.9%) intermediate-risk, 46 (22.4%) high-risk localized, 89 (43.4%) locally-advanced node-negative and 15 (7.3%) node-positive patients. The sensitivity, specificity, positive predictive value, and negative predictive value of the PSMA PET scan for nodal status were 37.5%, 98.2%, 80% and 89.4% respectively. The NPV was 89.4%, 93.8%, 87% and 86.6% for overall, intermediate-risk, high-risk localized and locally-advanced node-negative patients respectively. The median SUVmax of the primary prostate lesion in patients who were true negatives for nodes, as identified by the PSMA-PET scan, was significantly lower (12.8 vs 26.4, p<0.001) than that in patients who were false negative (cN0 on PSMA but pN+ in final pathology). Of the 190 cN0 patients, 20 had a false negative PSMA PET scan. Three of the 49 intermediate-risk patients had a false negative PSMA PET scan for nodes; the SUVmax scores of their prostate lesions were 26.59, 40.06 and 54.55 which were much higher than the median SUVmax score (12.8) in patients with a true negative scan. For the 135 high-risk cN0 patients, the 17 false negative patients had a median SUVmax of 24.37 compared to those with a true negative scan (13.57), p<0.001. CONCLUSIONS: The high NPV of PSMA-PET scan coupled with the SUVmax of the primary prostatic lesion can help avoid a PLND in intermediate and high-risk patients with a ‘negative’ PSMA-PET scan. The results can be considered as hypothesis generating and indicate the use of PSMA as a biomarker for predicting nodal disease. Further larger studies can help determine the ideal cut-off values for the SUVmax of the primary lesion. Source of Funding: No © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e326 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amandeep Arora More articles by this author Archi Agarwal More articles by this author Mahendra Pal More articles by this author Ganesh Bakshi More articles by this author Santosh Menon More articles by this author Gujela Ajit More articles by this author Gagan Prakash More articles by this author Expand All Advertisement PDF downloadLoading ...

MP11-06 THE PROGNOSTIC ROLE OF 68Ga-PSMA PET/CT AND THE IMPACT OF METASTASIS-DIRECTED THERAPY ON CANCER PROGRESSION IN MEN WITH BIOCHEMICAL RECURRENCE FROM PROSTATE CANCER. RESULTS FROM A LARGE, SINGLE INSTITUTION SERIES

MP11-06 THE PROGNOSTIC ROLE OF 68Ga-PSMA PET/CT AND THE IMPACT OF METASTASIS-DIRECTED THERAPY ON CANCER PROGRESSION IN MEN WITH BIOCHEMICAL RECURRENCE FROM PROSTATE CANCER. RESULTS FROM A LARGE, SINGLE INSTITUTION SERIES

A phase I/II dose-escalation study of fractionated 225Ac-J591 for progressive metastatic castration-resistant prostate cancer (mCRPC) in patients with prior treatment with 177Lu-PSMA.

TPS288 Background: As prostate-specific membrane antigen targeted radiotherapy (PSMA-TRT) is now an active standard-of-care treatment in mCRPC, ongoing studies with alternative approaches to targeting PSMA will increasingly need to consider the consequences of sequential PSMA-TRT exposure. Our past and ongoing investigations into antibody-based targeting (e.g., J591) and potent alpha emitting payloads (e.g., 225Ac) impact drug kinetics, biodistribution, and resultant clinical toxicities. In a first-in-human phase I dose-escalation study of 225Ac-J591, patients with mCRPC were treated with a single dose of 225Ac-J591 on seven dose levels, up to 93.3 KBq/kg without achievement of maximal tolerated dose (MTD). One patient treated at 80 KBq/kg developed dose-limiting toxicity (DLT) of Gr 4 anemia and thrombocytopenia, but 0 of 6 at 93.3 KBq/Kg had Gr &gt; 3 heme toxicity or Gr &gt; 2 non-heme toxicity. Although not intentionally preselected for prior exposure, 55% (12/22) of patients had 177Lu-PSMA previously. With approval of 177Lu vipivotide tetraxetan, we amended an ongoing phase I dose-escalation study to include a post-177-Lu-PSMA cohort. Methods: Entry criteria include progressive mCRPC by PCWG3 criteria, ECOG PS 0-2, intact organ function, and prior receipt of AR pathway inhibitor and chemotherapy (or refused/ineligible). There is no limit to prior lines of therapy except alpha-emitting therapies (i.e., PSMA-TRT, 223Ra) and in this amended dose-escalation cohort, all patients must have had prior treatment with 177Lu-PSMA. Treatment will be given in a single fractionated cycle of 225Ac-J591 administered on D1 and D15. The phase I component is a 3+3 dose-escalation study design with up to 18 patients, with the goal of identifying MTD. The phase II component will include up to 16-19 patients in a Simon 2-stage design with 90% power to exclude the null hypothesis (35% or fewer patients with PSA50). Eligible men with negative PSMA PET scans will be offered treatment with informed consent in an exploratory subgroup but will not be counted towards phase II efficacy. Secondary outcomes include radiographic response by PCWG3-modified RECIST 1.1 criteria and PSMA PET, biochemical and radiographic progression-free survival, circulating tumor cell counts, and overall survival. Patient reported outcomes, genomic, and immune analyses are exploratory. Enrollment to the post-177Lu-PSMA cohort began in August 2022. Clinical trial information: NCT04506567 .

Metastatic Carcinoma to the Brain with Mucinous Features in a Patient in Remission with History of Breast Lobular Carcinoma Triple Positive: A Case Report

Introduction: Breast cancer remains to be the most frequently diagnosed cancer in woman accounting for more than 2 million cases per year where it can metastasize to several organs in the body with brain metastasis being one of the most dreaded sequelae of it. Whole-brain radiosurgery, with or without surgical resection, or stereotactic radiosurgery remains to be the predominant treatment modality whereby surgical resection is limited to cases having a sole lesion identified or when located in excisable cortical regions. Case description: We presented the case of a 71-year old female patient with history of Lobular carcinoma in situ triple positive with brain metastatic carcinoma with mucinous features consistent with breast origin while being in remission after she underwent bilateral mastectomies 6 years prior to presentation with negative PET scan for any lesion other than that in the brain. Conclusion: Finding of brain metastasis with pathological features discordant with primary pathology of breast cancer, in a patient who is in remission years after undergoing bilateral mastectomies raises the question of the histological differentiation between the metastatic lesion and the primary source at the cellular level, and reflects on the relationship with receptor expression be it PR, ER or HER2.

Plasma phosphorylated tau181 predicts cognitive and functional decline.

To determine if plasma tau phosphorylated at threonine 181 (p-tau181) distinguishes pathology-confirmed Alzheimer's disease (AD) from normal cognition (NC) adults, to test if p-tau181 predicts cognitive and functional decline, and to validate findings in an external cohort. Thirty-one neuropathology-confirmed AD cases, participants with clinical diagnoses of mild cognitive impairment (MCI, N=91) or AD dementia (N=64), and NC (N=241) had plasma collected at study entry. The clinical diagnosis groups had annual cognitive (Mini-Mental State Examination, MMSE) and functional (Clinical Dementia Rating Scale, CDR) measures. NC (N=70), MCI (N=75), and AD dementia (N=50) cases from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used as a validation cohort. Plasma p-tau181 was measured using the Quanterix SiMoA HD-X platform. Plasma p-tau181 differentiated pathology-confirmed AD from NC with negative amyloid PET scans with an AUC of 0.93. A cut point of 3.44 pg/mL (maximum Youden Index) had a sensitivity of 0.77, specificity of 0.96. p-Tau181 values above the cut point were associated with the faster rate of decline in MMSE in AD dementia and MCI and a shorter time to a clinically significant functional decline in all groups. In a subset of MCI cases from ADNI, p-tau181 values above the cut point associated with faster rate of decline in MMSE, and a shorter time to a clinically significant functional decline and conversion to dementia. Plasma p-tau181 differentiates AD pathology cases from NC with high accuracy. Higher levels of plasma p-tau181 are associated with faster cognitive and functional decline.

Behavioral reaction to amyloid beta status disclosure

AbstractBackgroundLimited information exist regarding the reaction of cognitively unimpaired research participants to amyloid status disclosure and even more so in observational studies. We aimed to assess the associations of amyloid status disclosure with reported subjective memory concern, motivation to change lifestyle, anxiety, and depression.MethodResearch participants that take part in two observational studies and two clinical trials that incorporate amyloid‐PET where included. Participants received information regarding amyloid‐PET testing, results, and interpretation. They then performed an interview prior to PET scan and four‐to‐six‐month following result disclosure assessing their subjective memory concern, motivation to change lifestyle, anxiety, and depression from the possibility of a positive amyloid‐PET result.Result130 cognitively normal adults completed both the pre‐PET and post‐PET questionnaires. Only 11 had a positive amyloid‐PET result and thus were excluded from the analyses. Of the 119 subjects with a negative PET scan, 70 (59%) were females, mean age = 62Y (rang 44‐88Y), mean education = 16Y (4‐25), mean MMSE = 29 (24‐30); most (64%) reported no memory concerns or mild memory concerns (1/2 on a scale of 5). This increased to 94% at 4‐6 month following amyloid‐PET disclosure (Figure 1). Most (84%) had high or very high motivation to change lifestyle (4/5 in a scale of 5) in the pre‐PET assessment. This decreased to 30% in the post‐PET assessment. High and very high (4/5 in a scale of 5) anxiety and depression from a positive amyloid scan rates decreased from 25% to 0% and from 10% to 0%, respectively following a negative PET result disclosure (Figure 1). Although most individuals reported favorable post‐PET changes, a few subjects experienced increase in memory decline (N = 8), anxiety (N = 6) or depression (N = 1) following disclosure (Figure 2).ConclusionIn cognitively normal adults, the disclosure of a negative amyloid‐PET scan result was associated with a general “comforting” effect as reflected by less subjective memory concerns, anxiety, and depression, and lower motivation to perform lifestyle changes. By AAIC 2022, we anticipate more participants who are amyloid‐PET positive allowing to compare their behavioral changes after disclosure of amyloid results to the changes of those who are amyloid‐PET negative.

Free from Maintenance Drug Therapy in Multiple Myeloma (The FREEDMM Trial): A Pilot Study of Minimal Residual Disease (MRD)-Driven Discontinuation of Maintenance

Background Induction therapy followed by autologous stem cell transplant (ASCT) and maintenance is the current standard of care for the treatment of newly diagnosed multiple myeloma (NDMM). However, indefinite maintenance therapy after ASCT carries both significant clinical and financial toxicities. While minimal residual disease (MRD) testing has become part of routine standard of care, its use in guiding treatment decisions, in particular cessation of therapy, has not been established in the maintenance setting. We hypothesize that MRD monitoring could be used to guide clinical decision making, justifying cessation of maintenance therapy in a sub-group of patients with sustained MRD-negative remission. Study Design and Methods This is a phase 2 single-arm adaptive design study (NCT 05192122) for decision-making regarding maintenance therapy (Figure 1). Patients are eligible if they have a diagnosis of active MM, have completed at least 2 years of maintenance therapy post-ASCT, and meet International Myeloma Working Group (IMWG) criteria for very good partial response (VGPR) or complete response (CR). MRD testing is performed twice, at least one year apart, on bone marrow aspirate using next-generation sequencing (NGS) and MRD-negative status is defined at a threshold of 10-6. Patients with negative PET scan in VGPR or CR and sustained (i.e., twice, 1 year apart) MRD negative status discontinue maintenance therapy. MRD-positive patients continue continue maintenance and are taken off study. In patients who are MRD-negative and discontinue maintenance therapy, MRD testing will be re-assessed yearly for 3 years. At each time of MRD testing, MALDI-TOF spectrometry and measurement of circulating multiple myeloma cells (CMMCs) will be done in parallel to compare against MRD results. Health-related quality of life (HRQoL) will be assessed throughout and results on maintenance compared with those after discontinuation using the EORTC QLQ-MY20 questionnaire. This study will enroll 50 patients to address the primary objective of assessment for sustained MRD-negative status at 12 months after stopping maintenance therapy. For all patients, a 5-mL peripheral blood and bone marrow sample is collected and stored at the time of each standard of care bone marrow biopsy and will be used to characterize the immune microenvironment by Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) of paired peripheral blood and bone marrow in MRD-negative and MRD-positive patients as well as of patients progressing after stopping therapy. Preliminary Results Enrollment into FREEDMM trial began in December 2021, and to date 20 patients in CR have undergone a first bone marrow for MRD assessment, with results pending in 9 patients. The median age is 66.5 (range: 39-76) years, and the majority of patients are either Black (n=7; 35%) or Hispanic (n=7; 35%). One patient has high risk disease (17p deletion). The median number of years of maintenance therapy completed is 4.2 (range: 2.14-7.9) years. 17 (85%) patients had a negative MALDI-TOF test at the time of the first marrow. Seven (63.6%) of 11 patients were found to be MRD-negative. MALDI-TOF failed to accurately correlate with MRD results in 2 patients. 40 paired peripheral blood (n=20) and bone marrow aspirate (n=20) samples have been collected for CITE-seq analysis. Pilot CITE-seq experiments captured 6,700-11,000 cells with between 38,000-68,000 reads per cell on one MRD-negative and one MRD-positive bone marrow aspirate and paired peripheral blood sample. CITE-seq results for these 20 patients will be presented at the conference. Conclusion: This phase 2 trial applies a novel clinical trial design with an adaptive strategy to explore use of MRD testing as a guide to discontinuing maintenance therapy in myeloma and represents one of the first studies to explore in parallel various measures of disease monitoring (i.e., MRD, MALDI-TOF, CMMCs, CITE-seq). Ongoing results will be reported at the conference. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incorporation of Nelarabine (NEL), Pegylated Asparaginase (PEG) and Venetoclax (VEN) in the Frontline Therapy of Adult Patients with T-Acute Lymphoblastic Leukemia/T-Lymphoblastic Lymphoma (T-ALL/LBL)

Background: NEL is effective for patients (pts) with relapsed T-ALL/LBL, but its incorporation into the front-line therapy has not been investigated extensively in the adult population. In children, the addition of NEL to the induction regimen has shown to improve disease-free survival (DFS) but not the overall survival (OS). VEN has shown preclinical and clinical activity in relapsed T-ALL/LBL. We investigated the addition of NEL and PEG to the hyper-CVAD (HCVAD) regimen in adult pts with T-ALL/LBL. Further on, we explored the safety and efficacy of adding VEN to this regimen. Methods: Pts with previously untreated or minimally pre-treated T-ALL/LBL were eligible if they had an ECOG PS ≤3, creatinine ≤ 2 mg/dL, total bilirubin ≤ 2 mg/dL and ALT/AST ≤ 4 x ULN. Pts received 8 cycles of HCVAD (cycles 1,3, 5, 7) alternating with high dose ara-C and methotrexate (MTX) (cycles 2, 4, 6, 8) at approximately 3-week intervals. Two cycles of NEL (650 mg/m2 daily x 5) were initially administered after cycle 8 (cohort 1). Later, after a protocol amendment, they were administered after cycle 4 and cycle 5 (cohort 2). Subsequently, the protocol was amended to add PEG (1500 IU/m2 capped at 3750 IU) on day 5 of the NEL cycles (cohort 3) and more recently, VEN 400 mg daily was added on the first 7 days of each of 8th cycle of therapy (cohort 4) and this was later modified to be given for 7 days during the induction cycle and reduced to 3 days per cycle post-induction only in pts with ETP-ALL or those with persistent MRD. All other pts did not receive VEN after cycle 1 (cohort 5). Pts with ETP-ALL were referred for allogeneic stem cell transplant in first complete remission (CR). After the completion of the intensive phase, pts in all cohorts received 30 cycles of maintenance therapy with monthly POMP and early intensification with NEL/PEG on cycles 6 and 7 and late intensification with MTX/PEG in cycle 18 and HCVAD on cycle 19. All pts received 8 intrathecal chemotherapy with MTX alternating with ara-C and mediastinal radiation was considered in pts with bulky mediastinal disease. Results: Between 8/2007 and 6/2022, 128 pts were enrolled in the 5 study cohorts sequentially (cohort 1= 30, 2= 49, 3=17, 4=16, 5=16) (Table). Seventy-seven pts had T-ALL, 50 T-LBL and 1 biphenotypic T/myeloid leukemia. Median age was 35 yrs. (range 18-78), 98 pts were male (77%) and 110 pts (86%) had PS 0-1. In pts with T-ALL, median bone marrow blast percentage was 83% (range, 20-97) Six pts (5%) had CNS disease at presentation. Cytogenetics were diploid in 82 pts (64%), abnormal in 36 (28%), and unavailable in 10 pts (8%). Pts were further characterized as early T-cell precursor (ETP; n=24), near ETP (ETP + CD5) (N=19), early-non-ETP (n=3), thymic (n=54), mature (n=12), not otherwise specified (NOS; n=16). Twenty-five pts had received 1-2 cycles of therapy prior to enrollment, with 18 having achieved CR. The 30-day mortality was 0%. One hundred and twelve pts (88%) had ≥ 1 grade 3/4 non-hematological treatment-emergent adverse events (TEAE) with the most frequent grade 3/4 TEAEs being neutropenic infections in 96 pts (75%) and elevated liver enzymes in 25 pts (20%). The overall response rate (CR/CRi/PR) was 98% with CR/CRp in 120/128 pts (94%), PR in 5 (4%), and no response in 3 (2%). The median number of cycles to response (including a negative PET scans) was 1 (range 1-10). CR/CRp rate in T-ALL was 91% and T-LBL was 98%. At a median follow-up of 50 months (1-174), 84 patients (66%) are alive with a 5-year PFS and OS of 60% and 61% (Figure 1) and 79 pts (62%) remain in CR. Conclusion: The addition of NEL/PEG cycles to the HCVAD regimen is feasible. The addition of VEN to each cycle is associated with significant myelosuppression. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated with Expansion and Maturation of NK Cells

ABSTRACT Background. Hodgkin Lymphoma (HL) Hodgkin Lymphoma (HL) is a B-Cell neoplasia characterized by a high degree of response to chemotherapy and an overall favourable outcome in responding patients. Despite the efficacy of first line therapy, however, about 30% of patients affected by HL are either refractory or eventually relapse (R/R) after first or second line therapy followed by autologous hemopoietic stem cell transplantation (ASCT). Immune checkpoint inhibitors (CI) have demonstrated clinical activity in HL patients relapsing after ASCT, although only 20% complete response (CR) rate are usually observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Aims. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI) and to investigate the lymphocyte subpopulation involved in the mechanism of response to CI in HL. Results. Seventeen patients with relapse/refractory (R/R) HL (median age 29 years; range 18-65), underwent lymphocyte apheresis after first line chemotherapy and then proceeded to salvage therapy. Subsequently, 12 patients with progressive disease at ASCT received early post-transplant CI supported with four ALI, whereas 5 responding patients received ALI alone, as a control cohort. Most patients showed CMV seropositivity at the time of enrolment, without signs of active infection (positive anti-CMV IgG, negative IgM and undetectable CMV DNA). No adverse events were recorded, specifically, no immune-related toxicity was observed and none of the patients showed CMV reactivation. All patients receiving ALI + CI (treated patients) achieved negative PET scan CR and 11/12 are alive and disease-free after a median follow-up of 33 months. The only relapse occured 23 months after last ALI. Six of the responding patients underwent subsequent allogeneic SCT in a CR status and 1 patients are currently waiting for transplantation. Two of the patients in the control arm relapsed after a median of 6 months (4-8 months) Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in ALI plus nivolumab-treated patients as compared to control patients (Fig.1). In detail, different patterns of NK cell development could be identified. Indeed, starting from one month after transplantation, in the group of patients undergoing ALI plus nivolumab, a relevant fraction of NK cells displayed a mature phenotype characterized by a CD56dimCD16bright expression (Fig. 1). On the contrary, in control patients, NK cells were characterized by a more immature phenotype (high frequencies of CD56brightCD16neg/dim NK cells) even at late time points (three months) after transplantation (Fig. 1). This event occurred in all the treated (ALI + nivolumab) patients analyzed (Fig. 1). Finally, PB from patients undergoing ALI + nivolumab was enriched in unconventional CD56dimCD16dim NK cells (Fig. 1). One month after transplantation, CD94/NKG2A+ KIR- NK cells were largely predominant in all patients, whereas CD94/NKG2A- KIR+ NK cells were present in low proportions. An increase of CD94/NKG2A- KIR+ subset occurred primarily in treated patients starting from t2. At t3, the significant increase of CD94/NKG2A- KIR+ NK cells occurred in the treated group but not in the control group . This event occurred in all the treated (ALI + nivolumab) patients analyzed, regardless of their serological status for HCMV, but was more evident in treated patients who were seropositive for HCMV. Remarkably, PB from HCMV seropositive patients undergoing ALI + nivolumab became enriched over time in differentiated NK cells characterized by high expression of NKG2C receptor (the activating counterpart of NKG2A), as compared to HCMV+ control patients. This subset represents the so-called "adaptive" NK cell population that usually increases during HCMV infection/reactivation. In this case, however, this event occurred in the absence of HCMV reactivation, and only in HCMV seropositive patients treated with ALI + nivolumab. Conclusions. Our data show anti-tumour activity with good tolerability of ALI + CI for R/R HL and suggest that this setting may accelerate NK cell development/maturation and favour the expansion of the "adaptive" NK cell compartment, especially in patients with CMV seropositivity, in the absence of CMV reactivation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Diagnostic efficacy of positron emission computerized tomography scans in suspicious laryngeal findings postorgan preservation treatment.

Larynx preservation protocols (LPP) for glottic primary squamous cell carcinoma has gained popularity worldwide. Direct laryngoscopy (DL) with biopsy is mandated when recurrence is suspected. The efficacy of 18Fluoro-deoxy-glucose positron emission computerized tomography (PET-CT) as alternative first-line diagnostic investigation in suspected recurrence was evaluated. A retrospective study of patients with suspicious fiber-optic findings at more than 12 weeks after LPP. Sensitivity, specificity, and the negative predictive value (NPV) of DL and PET-CT were compared. Seventy-two patients presenting 105 cases of suspicious events were included in this study. Fifty-two events were initially investigated by DL and 53 events by PET-CT. The sensitivity of DL and PET-CT was 56.25% and 100%, respectively. The NPV was 84% for DL and 100% for PET-CT (p=0.015). Negative PET scans after LPP are highly accurate in ruling out recurrent/persistent disease and may spare the patient from negative biopsies.