Citations

e18073 Background: Selpercatinib is a highly selective RET inhibitor that is used for the treatment of RET-mutant medullary thyroid cancers, but its efficacy and safety is not fully understood. Our objective is to summarize available literature on the safety and efficacy profile of Selpercatinib. Methods: A search was conducted on PubMed, Embase and Cochrane from foundation to 31st January 2024. Patients aged above 18 with Advanced RET-Altered Medullary Thyroid Cancers who received Selpercatinib were identified. Data abstraction was done based on objective response rate, complete response rate, any grade adverse effect (AE) and grade ≥3 AE. Analysis was done using R (v.4.3) and reported as proportions with respective 95% confidence intervals (CI) on forest plots. Results: Four studies were identified that reported the use of Selpercatinib in Advanced RET-Altered Medullary Thyroid Cancers. Our analysis showed that the pooled proportion of objective response rate and complete response rate was 74.8% (95% CI: 70.1% – 79%) and 4.9% (95% CI: 3.1% – 7.7%) respectively. Pooled proportion of patients experiencing any grade AE and grade ≥3 AE was 93.4% (95% CI: 90.4% – 95.6%) and 46.2% (95% CI: 41.1% – 51.3%) respectively. Conclusions: Selpercatinib is a novel RET inhibitor which has potential use against RET-Altered Thyroid Cancers. It has an overall acceptable safety and efficacy profile. However it requires further studies to establish its adverse effects and clinical application. [Table: see text]

Purpose: We describe the communication challenges of four patients with a neurodegenerative disorder consistent with behavioral variant frontotemporal dementia (bvFTD), characterized by early behavioral and personality changes. By describing their clinical profiles, we identify common barriers to functional communication in this population and provide recommendations for how speech-language pathologists (SLPs) might contribute to minimizing them. Method: Four patients with bvFTD were selected from a cohort of patients with progressive communication impairments. Three of them returned for at least one follow-up visit. Case histories are presented along with the results of comprehensive speech and language, neuropsychological, and neurological testing. Results: At the time of initial evaluation, patients were between the ages of 54 and 66 years and had been experiencing symptoms for 1.5–6 years. Consistent with their bvFTD diagnoses, all patients had prominent behavioral and personality changes that impacted communication. Patients 1 and 2 also had mild aphasia at enrollment, primarily characterized by anomia and loss of word meaning. Patients 3 and 4 both had apraxia of speech and moderate-to-severe aphasia at enrollment with prominent anomia and agrammatism. All four patients had impaired executive functioning and relative sparing of visuospatial skills; episodic memory was also impaired for Patients 2 and 4. Even though functional communication was progressively limited for all patients, none of them received regular support from an SLP. Conclusions: This case series adds to a scant, but growing, literature demonstrating that patients with bvFTD have communication impairments. SLPs are uniquely positioned to identify barriers to functional communication and to provide tailored strategy training to the patients and their care partners over the course of their disease. Systematic evaluation of the efficacy of treatment in this population would be valuable. Supplemental Material: https://doi.org/10.23641/asha.25933762

e16531 Background: Hypoxia-inducible Factor-2α (HIF-2α) is a transcription factor that accumulates in clear cell renal cell carcinoma (ccRCC) and is responsible for genes involved in oncogenesis. Belzutifan is a HIF-2α inhibitor that has shown promising anti-tumor effects in patients with ccRCC. Our objective is to summarize the available literature on the safety and efficacy profile of the drug. Methods: An electronic search was conducted on PubMed, Embase, and Cochrane from inception till January 31st, 2024. We identified patients aged ≥ 18 years with ccRCC who received Belzutifan. We extracted data on objective response rate, complete response rate, any grade adverse effect (AE) and grade ≥3 AE. Data was analyzed using R (v.4.3) and reported as proportions with respective 95% confidence intervals (CI) on forest plots. Results: Three studies (n=168 patients) were identified that reported the use of Belzutifan in ccRCC. Our analysis showed that pooled proportion of objective response rate and complete response rate was 35% (95% CI: 24% – 47%) and 1% (95% CI: 0% – 5%) respectively. Pooled proportion of patients experiencing any grade AE and grade ≥3 AE was 98% (95% CI: 95% – 99%) and 49% (95% CI: 29% – 69%) respectively. Conclusions: Belzutifan is a novel drug that inhibits HIF-2α which in turn results in anti-tumor effects of the drug against ccRCC. The drug has an acceptable safety and efficacy profile from limited data but more studies are needed to establish a complete picture of drug’s adverse effects and clinical benefits. Pooled proportion of patients developing (A) Objective Response, (B) Complete response (C) Any adverse effect and (D) Grade ≥3 adverse effects. [Table: see text]

e24003 Background: Cancer patients undergoing chemotherapy suffer from a variable degree of cancer therapy–related cardiac dysfunction and heart failure (HF). It is known that sodium glucose co-transporter 2 (SGLT2) inhibitors improve outcomes in patients with HF independent of diabetes mellitus and left ventricular ejection fraction; our study aims to investigate the potential benefits of SGLT2 inhibitory therapy specifically in cancer patients undergoing chemotherapy. Methods: We performed an electronic search on PubMed, Embase, and Cochrane, from the inception of databases till January 29, 2024, to identify all the articles that compared the use of SGLT2 inhibitors in adult (≥18 years) with type 2 diabetes mellitus and exposure to cardiotoxic antineoplastic therapy, subsequently diagnosed with cardiomyopathy, heart failure, or LVEF < 40%. The data was extracted and pooled using a random effects model to calculate the odds ratio (OR) with a respective 95% confidence interval (CI). R software (v.4.3) was used for all statistical analyses. Results: Our search identified three observational studies with a total of 3,164 patients (SGLT2- inhibitor group: 1,550; Control group: 1,614). We found that the use of SGLT2 inhibitors was associated with a lower risk of all-cause mortality (OR: 0.25 [0.20, 0.31]; I2 = 16%; p < 0.001), hospitalizations from heart failure (OR: 0.25 [0.10, 0.62]; I2 = 0%; p = 0.003), and acute exacerbation of heart failure (OR: 0.35 [0.27, 0.47]; I2 = 0%; p < 0.001). Conclusions: Our findings suggest a favorable association between the use of SGLT2 inhibitors and reduced mortality, as well as improved cardiac clinical outcomes in cancer patients undergoing chemotherapy. However, further validation through large-scale studies and randomized controlled trials across diverse malignancies is warranted to establish the efficacy of these drugs. [Table: see text]

AbstractIntroduction/AimsMany people living with amyotrophic lateral sclerosis (PALS) report restrictions in their day‐to‐day communication (communicative participation). However, little is known about which speech features contribute to these restrictions. This study evaluated the effects of common speech symptoms in PALS (reduced overall speaking rate, slowed articulation rate, and increased pausing) on communicative participation restrictions.MethodsParticipants completed surveys (the Communicative Participation Item Bank‐short form; the self‐entry version of the ALS Functional Rating Scale‐Revised) and recorded themselves reading the Bamboo Passage aloud using a smartphone app. Rate and pause measures were extracted from the recordings. The association of various demographic, clinical, self‐reported, and acoustic speech features with communicative participation was evaluated with bivariate correlations. The contribution of salient rate and pause measures to communicative participation was assessed using multiple linear regression.ResultsFifty seven people living with ALS participated in the study (mean age = 61.1 years). Acoustic and self‐report measures of speech and bulbar function were moderately to highly associated with communicative participation (Spearman rho coefficients ranged from rs = 0.48 to rs = 0.77). A regression model including participant age, sex, articulation rate, and percent pause time accounted for 57% of the variance of communicative participation ratings.DiscussionEven though PALS with slowed articulation rate and increased pausing may convey their message clearly, these speech features predict communicative participation restrictions. The identification of quantitative speech features, such as articulation rate and percent pause time, is critical to facilitating early and targeted intervention and for monitoring bulbar decline in ALS.

AbstractProgressive apraxia of speech (PAOS) is a 4R tauopathy characterized by difficulties with motor speech planning. Neurodegeneration in PAOS targets the premotor cortex, particularly the supplementary motor area (SMA), with degeneration of white matter (WM) tracts connecting premotor and motor cortices and Broca's area observed on diffusion tensor imaging (DTI). We aimed to assess flortaucipir uptake across speech‐language‐related WM tracts identified using DTI tractography in PAOS. Twenty‐two patients with PAOS and 26 matched healthy controls were recruited by the Neurodegenerative Research Group (NRG) and underwent MRI and flortaucipir‐PET. The patient population included patients with primary progressive apraxia of speech (PPAOS) and non‐fluent variant/agrammatic primary progressive aphasia (agPPA). Flortaucipir PET scans and DTI were coregistered using rigid registration with a mutual information cost function in subject space. Alignments between DTI and flortaucipir PET were inspected in all cases. Whole‐brain tractography was calculated using deterministic algorithms by a tractography reconstruction tool (DSI‐studio) and specific tracts were identified using an automatic fiber tracking atlas‐based method. Fractional anisotropy (FA) and flortaucipir standardized uptake value ratios (SUVRs) were averaged across the frontal aslant tract, arcuate fasciculi, inferior frontal‐occipital fasciculus, inferior and middle longitudinal fasciculi, as well as the SMA commissural fibers. Reduced FA (p < .0001) and elevated flortaucipir SUVR (p = .0012) were observed in PAOS cases compared to controls across all combined WM tracts. For flortaucipir SUVR, the greatest differentiation of PAOS from controls was achieved with the SMA commissural fibers (area under the receiver operator characteristic curve [AUROC] = 0.83), followed by the left arcuate fasciculus (AUROC = 0.75) and left frontal aslant tract (AUROC = 0.71). Our findings demonstrate that flortaucipir uptake is increased across WM tracts related to speech/language difficulties in PAOS.

Case: A 20-year-old woman presented with a unipolar, 1.8 × 1.8-cm osteochondral defect of the left acetabulum. Osteochondral allograft transplantation was performed using a medial tibial plateau allograft resulting in excellent clinical outcomes across 4 different outcome scores and maintenance of the joint space at 4.3 years postoperatively. Conclusion: Although previous literature has demonstrated long-term clinical success of osteochondral allograft transplantation in knee, excellent clinical outcomes can also be obtained in the hip. Thus, osteochondral allograft transplantation may be a viable treatment option for adolescents and young adults with concomitant cartilage and subchondral bone hip defects.

AbstractBackgroundPassively collected smartphone sensor data provide an opportunity to study physical activity and mobility unobtrusively over long periods of time and may enable disease monitoring in people with amyotrophic lateral sclerosis (PALS).MethodsWe enrolled 63 PALS who used Beiwe mobile application that collected their smartphone accelerometer and GPS data and administered the self‐entry ALS Functional Rating Scale‐Revised (ALSFRS‐RSE) survey. We identified individual steps from accelerometer data and used the Activity Index to summarize activity at the minute level. Walking, Activity Index, and GPS outcomes were then aggregated into day‐level measures. We used linear mixed effect models (LMMs) to estimate baseline and monthly change for ALSFRS‐RSE scores (total score, subscores Q1–3, Q4–6, Q7–9, Q10–12) and smartphone sensor data measures, as well as the associations between them.FindingsThe analytic sample (N = 45) was 64.4% male with a mean age of 60.1 years. The mean observation period was 292.3 days. The ALSFRS‐RSE total score baseline mean was 35.8 and had a monthly rate of decline of −0.48 (p‐value <0.001). We observed statistically significant change over time and association with ALSFRS‐RSE total score for four smartphone sensor data‐derived measures: walking cadence from top 1 min and log‐transformed step count, step count from top 1 min, and Activity Index from top 1 min.InterpretationSmartphone sensors can unobtrusively track physical changes in PALS, potentially aiding disease monitoring and future research.

1037 Background: TBCRC041, a randomized phase 2 trial of alisertib (A) ± fulvestrant (F) in women with HR+/HER2- MBC demonstrated promising clinical activity for alisertib (1). Interrogation of baseline (PreC1) and end of cycle 1 (EOC1) cfDNA and CTCs may identify biomarkers associated with response to A±F. Methods: Plasma cfDNA was sequenced using the Guardant INFINITY platform, which includes genomic and methylated tumor fraction (mTF) analysis. Pathogenic variants were determined using publicly available databases and Mayo Clinic annotation pipelines. CTCs were identified as nucleated, EpCAM+/ cytokeratin+/ CD45- cells and assessed for ER/HER2 staining (RareCyte, Seattle). PFS was defined as the time from randomization to progression or death. EOC1-PFS differs from PFS as time starts at C2D1. Stratified log-rank tests and conditional Cox modeling were used to assess whether PFS or EOC1-PFS differed by mutations in ESR1 or PIK3CA, pre-CTC ≥ 5, or mTF>1%. Results: Of the 91 eligible pts, 84 progressed, and 73 were deceased. In the 86 pts with PreC1-cfDNA results, variants were identified in ESR1 (42; 48.8%), PIK3CA (36; 41.9%), AKT1 (7; 8.1%), PTEN(7; 8.1%), BRCA1 (4; 4.7%), and BRCA2 (7; 8.1%). Pts with a PIK3CAmut had significantly decreased PFS (HR 1.8; 95%CI: 1.1 -2.9, p=0.014) but not by ESR1mut status (p=0.583). PreC1 and EOC1-mTF were determined for 78 and 76 pts, respectively. PreC1-mTF was 0-1% in 21; 1.1-10.0% in 27; and 10.1-100% in 30. mTF levels remained between 0-1% in 17 pts fell to 0-1% in 11 pts, and was 0-1% in 5 pts without a preC1-mTF determination. PFS did not differ with respect to PreC1-mTF (p=0.210), but EOC1-PFS was worse in pts with mTF >1% (HR 3.0; 95%CI: 1.6 -5.2, p<0.001). PreC1 and EOC1-CTC were determined for 78 and 76 pts. 36 (46.2%) pts had a PreC1 CTC count ≥ 5. EOC1-CTC levels remained at (n=17) or increased to (n=1) ≥ 5 and was ≥ 5 in 2 pts without a preC1-CTC determination. EOC1-PFS was not significantly different for EOC1-CTC ≥ 5 (p=0.065), but was significantly decreased in pts with PreC1-CTC≥5 (HR=1.8; 95%CI: 1.1-3.0; p=0.018). Broader cfDNA NGS panel and CTC-derived ER/HER2 staining results will be presented at the meeting. Conclusions: Among patients receiving A±F, PFS varied based on the PIK3CAmutation status. cfDNA and CTC assessment PreC1 and EOC1 provided complementary information. Further validation in larger datasets is needed. 1. JAMA Oncol 2023;9:815. Clinical trial information: NCT02860000 .