Citations

TPS9606 Background: For patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) provides important staging and prognostic information that guides surveillance and adjuvant systemic therapy decisions. At most centers, SLNB is indicated for patients with cutaneous melanoma with at least a 5% risk of having nodal metastases, typically melanomas ≥ 0.8 mm in thickness or thinner lesions with high-risk features such as elevated mitotic rate and/or ulceration. SLNB, generally involving a separate incision, does carry a small but measurable risk of complications including seroma, infection and rarely lymphedema, and most patients have negative sentinel lymph nodes. Currently, there is an unmet clinical need to identify patients who may safely forgo SLNB due to a low (<5%) risk of nodal metastasis, who otherwise meet established criteria for SLNB. Previously, a model consisting of gene expression profile (GEP) of the primary tumor combined with clinicopathological features (CP) has been developed to identify melanoma patients with a low risk of having a positive SLNB. The model has also been validated in multiple retrospective studies. The aim of the MERLIN_001 registry study is to prospectively validate the CP-GEP model in an independent multicenter cohort of primary cutaneous melanoma patients who undergo SLNB for standard indications. Methods: In the next two years, a total of 10 centers across the US will enroll 2,340 patients with clinically node-negative cutaneous melanoma undergoing SLNB using current guideline indications and will follow these patients for 5 years (ClinicalTrials.gov identifier: NCT04759781). Enrollment of patients started in September 2021 and 242 patients have been enrolled as of February 1, 2022. FFPE material from the initial melanoma biopsy will be used to assess the GEP of the primary melanoma. The CP-GEP probability scores will be expressed as a binary classification (Low Risk or High Risk for nodal metastasis) and will be compared to SLN pathology. Performance metrics for CP-GEP will be evaluated and will include: Negative Predictive Value, Positive Predictive Value, Sensitivity and Specificity, and the corresponding 95% confidence intervals. Risk for nodal metastasis will be calculated for Low Risk and High Risk CP-GEP patients. Finally, the performance of CP-GEP to stratify patients according to risk of recurrence (local, regional, distant, death) will also be studied, since data will be collected for up to 5 yrs. Clinical trial information: NCT04759781.

518 Background: Body Mass Index (BMI) impacts breast cancer risk and prognosis. Conflicting results have been published regarding BMI as a predictive factor for endocrine therapy benefit. CDK4/6 inhibitors (CDK4/6i) in combination with endocrine treatment (ET) are standard-of-care treatments for metastatic hormone receptor-positive breast cancer. In contrast to cytotoxic chemotherapy, CDK4/6i are given at a fixed dose irrespective of BMI or weight. The PALLAS trial compared the combination of the CDK4/6i palbociclib and adjuvant ET to ET alone in the early breast cancer setting. This analysis investigates the impact of BMI on the efficacy and the side effect profile of palbociclib (P) in the PALLAS trial. Methods: In this pre-planned analysis, patients (pts) enrolled in PALLAS were categorized according to BMI as underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2) and obese (³30 kg/m2), respectively. Adverse event differences were assessed with Chi-squared tests. Time to early discontinuation of P was analyzed with Fine and Gray competing risk models. Cox models were used to investigate the association between BMI category and time to invasive disease-free survival (iDFS). Results: Of a total of 5698 pts included in this analysis, 68 (1.2%) were underweight, 2082 (36.5%) normal weight, 1818 (31.9%) overweight and 1730 (30.4%) obese at baseline. Significantly different rates of all grade neutropenia were observed in normal weight, overweight and obese pts with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese pts was associated with a significant lower treatment discontinuation rate over time when compared to normal weight patients (overweight vs normal weight: HR 0.73 CI 0.63-0.84, p<0.0001, and obese vs normal weight: HR 0.65 CI 0.56-0.75, p<0.0001). In pts treated with P, neutropenia was the primary toxicity leading to treatment discontinuation in 21.1% of normal weight pts, 14.0% of overweight pts and 5.9% obese pts, respectively. Despite these observations, there was no statistically significant improvement in iDFS with the addition of P to ET in any weight category (normal weight HR 0.84 CI 0.63-1.12, overweight HR 1.10 CI 0.82-1.49 and obese HR 0.95 CI 0.69-1.30). Conclusions: This pre-planned analysis of outcomes by BMI in the PALLAS trial demonstrates significantly less frequent and less severe neutropenia in overweight and obese pts compared to those with normal weight, leading to significant lower treatment discontinuation rates. However, no difference in iDFS outcomes by BMI was observed. Additional long-term follow-up will further evaluate whether BMI ultimately impacts outcome. Clinical trial information: NCT02513394.

AbstractIntroductionWe investigated the association of the area deprivation index (ADI) with cognitive decline, mild cognitive impairment (MCI), and dementia in older adults (≥50 years old). ADI is a neighborhood socioeconomic disadvantage measure assessed at the census block group level.MethodsThe study included 4699 participants, initially without dementia, with available ADI values for 2015 and at least one study visit in 2008 through 2018. Using logistic regression and Cox proportional hazards models with age as the time scale, we assessed the odds for MCI and the risk for dementia, respectively.ResultsIn cognitively unimpaired (CU) adults at baseline, the risk for progression to dementia increased for every decile increase in the ADI state ranking (hazard ratio = 1.06, 95% confidence interval (1.01–1.11), P = .01). Higher ADI values were associated with subtly faster cognitive decline.DiscussionIn older CU adults, higher baseline neighborhood socioeconomic deprivation levels were associated with progression to dementia and slightly faster cognitive decline.Highlights The study used area deprivation index, a composite freely available neighborhood deprivation measure. Higher levels of neighborhood deprivation were associated with greater mild cognitive impairment odds. Higher neighborhood deprivation levels were associated with higher dementia risk.

Abstract PET imaging plays an essential role in achieving earlier and more specific diagnoses of dementia syndromes, important for clinical prognostication and optimal medical management. This has become especially vital with the recent development of pathology-specific disease-modifying therapy for Alzheimer disease, which will continue to evolve and require methods to select appropriate treatment candidates. Techniques that began as research tools such as amyloid and tau PET have now entered clinical use, making nuclear medicine physicians and radiologists essential members of the care team. This review discusses recent changes in the understanding of dementia and examines the roles of nuclear medicine imaging in clinical practice. Within this framework, multiple cases will be shown to illustrate a systematic approach of FDG PET interpretation and integration of PET imaging of specific molecular pathology including dopamine transporters, amyloid, and tau. The approach presented here incorporates contemporary understanding of both common and uncommon dementia syndromes, intended as an updated practical guide to assist with the sophisticated interpretation of nuclear medicine examinations in the context of this rapidly and continually developing area of imaging.

Background: Cerebral microbleeds (CMBs) are a common vascular pathology associated with future intracerebral hemorrhage. Plasma biomarkers of amyloid, tau, and neurodegeneration may provide a screening avenue to identify those with CMBs, but evidence is conflicting. Objective: To determine the association between plasma biomarkers (Aβ40, Aβ42, t-tau, p-tau181, p-tau217, neurofilament light chain (NfL)) and CMBs in a population-based study of aging and whether these biomarkers predict higher signal on Aβ-PET imaging in patients with multiple CMBs. Methods: 712 participants from the Mayo Clinic Study of Aging with T2* GRE MRI and plasma biomarkers were included. Biomarkers were analyzed utilizing Simoa (Aβ40, Aβ42, t-tau, NfL) or Meso Scale Discovery (p-tau181, p-tau217) platforms. Cross-sectional associations between CMBs, plasma biomarkers and Aβ-PET were evaluated using hurdle models and multivariable regression models. Results: Among the 188 (26%) individuals with≥1 CMB, a lower plasma Aβ42/Aβ40 ratio was associated with more CMBs after adjusting for covariables (IRR 568.5 95% CI 2.8–116,127). No other biomarkers were associated with risk or number CMBs. In 81 individuals with≥2 CMBs, higher plasma t-tau, p-tau181, and p-tau217 all were associated with higher Aβ-PET signal, with plasma p-tau217 having the strongest predictive value (r2 0.603, AIC –53.0). Conclusion: Lower plasma Aβ42/Aβ40 ratio and higher plasma p-tau217 were associated with brain amyloidosis in individuals with CMBs from the general population. Our results suggest that in individuals with multiple CMBs and/or lobar intracranial hemorrhage that a lower plasma Aβ42/Aβ40 ratio or elevated p-tau217 may indicate underlying cerebral amyloid angiopathy.

Abstract Although costimulatory molecules have been shown to boost antitumor immune responses, their significance in stomach adenocarcinoma (STAD) is unknown. The purpose of this study was to examine the gene expression patterns of costimulatory molecule genes in STAD and to develop a predictive signature to aid in therapy selection and outcome prediction. We used 60 costimulatory family genes from prior research to conduct the first complete costimulatory molecule analysis in STAD patients. For the two groups discovered, consensus clustering analysis based on these 60 genes indicated unique distribution patterns and prognostic differences. Then, using Lasso and Cox regression analysis, 9 costimulatory molecular gene pairs (CMGPs) of prognostic value were discovered. With these 9 CMGPs, we were able to develop a costimulatory molecule-related prognostic signature, which performed well in an external dataset. For STAD patients, the signature was proved to be a risk factor independent of clinical characteristics, indicating that this may be employed in conjunction with clinical considerations. An further connection between the signature and immunotherapy response was discovered. People who had high mutation rates, an abundance of infiltrating immune cells, and an immunosuppressive milieu were classed as high-risk. It is possible that patients classed as high-risk have a better prognosis for immunotherapy since these patients have greater cytolytic activity scores and immunophenoscores of CTLA4 and PD-L1/PD-L2 blocker As a consequence, clinicians might use our signature to better assess patient prognosis and develop treatment plans.

Introduction: Cerebrovascular disease (CVD) and neuropsychiatric symptoms (NPS) are common in older adults and are independently associated with cognitive impairment. In addition, vascular depression (a late-life depression) is hypothesized to be associated with cerebrovascular pathology. Hypothesis: CVD pathology imaging biomarkers (e.g., white matter hyperintensities (WMH), infarctions) are associated with depression and anxiety, and both (depression/anxiety and CVD imaging biomarkers) are independently associated with mild cognitive impairment (MCI). Methods: This cross-sectional study included 1739 Mayo Clinic Study of Aging participants (≥50 years old) without dementia, with comprehensive cognitive evaluations and available data on the Beck Depression Inventory II (BDI), the Beck Anxiety Inventory (BAI) and imaging CVD biomarkers via FLAIR-MRI (i.e., WMH% of total intracranial volume (TIV) and brain infarctions). We used linear and logistic regression models to examine the associations adjusting for age, sex, education, and apolipoprotein E ε4 status. Results: Participants’ mean age (SD) was 71.11 (10.61) years (53.3% males). Higher WMH% TIV burden was significantly associated with higher BDI (b= 0.082, 95%CI: 0.031, 0.133), p=0.002) and BAI scores (b= 0.088, 95%CI: 0.037, 0.140), p=0.001); the presence of infarctions was also associated with a higher BDI score. Both WMH %TIV burden (OR: 1.20 (95%CI:1.05, 1.38), p=0.008) and BDI score (OR: 1.38 (95%CI:1.21, 1.57), p<0.001) were significantly associated with MCI when included simultaneously in the model. We observed similar associations for CVD biomarkers and BAI score with MCI. Conclusions: CVD imaging biomarkers and NPS, as measured by BDI and BAI scores, could represent two distinct processes associated with cognitive impairment. Studies are ongoing to further examine these associations and delineate how CVD, NPS, and other pathophysiology processes (e.g., Alzheimer’s disease) interact and are associated with cognitive impairment.