Citations

Abstract Purpose The thyroid-stimulating hormone receptor (TSHR) is a cell-surface receptor predominantly expressed on benign and malignant thyroid cells, making it a viable target for developing radiotheranostics for metastatic thyroid cancer imaging and therapy. This study reports the radiosynthesis and preclinical evaluation of a 64Cu-labelled human antibody for positron emission tomography (PET) imaging of TSHR expression in thyroid cancer mouse models. Methods Human anti-TSHR recombinant antibody K1-70™ (TSHR-Ab) was conjugated with a bifunctional chelator, 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA), and then labelled with [64Cu]Cu2+, yielding radiotracer [64Cu]Cu-NOTA-TSHR-Ab. The specificity and binding affinity of the radiotracer to TSHR-positive (THJ529TTSHR(+)) or wild-type (THJ529TWT) cells were assessed in vitro. A series of immnuoPET imaging with [64Cu]Cu-NOTA-TSHR-Ab were conducted in mice bearing dual-flank tumors (THJ529TWT on the left and THJ529TTSHR(+) on the right) at multiple time points (1, 2, 4, 18, 24, and 48 h) post-injection (p.i.). Radiotracer co-injection studies with varying doses of unlabelled (cold) TSHR-Ab (100, 50, 25, 0 µg) were studied to assess its effect on radiotracer uptake in tumors and off-target organs. Biodistribution and immunohistochemistry (IHC) were performed to verify the immnuoPET imaging results. Results [64Cu]Cu-NOTA-TSHR-Ab was synthesised with a radiochemical yield of 46.89 ± 3.74%, radiochemical purity of 98.77 ± 0.89%, and specific activity >1.42 GBq/mg (n = 5). In vitro cell studies demonstrated [64Cu]Cu-NOTA-TSHR-Ab had high specificity and nanomolar affinity for THJ529TTSHR(+) cells, with a dissociation constant (Kd) of 4.74 nM and an inhibition constant (Ki) of 0.92 nM. The immnuoPET imaging studies showed that the radiotracer could reach tumor quickly and showed high uptake in TSHR-positive thyroid tumors (SUVmax: 3.63 ± 0.42, 3.82 ± 0.44, and 4.09 ± 0.56 at 18, 24, and 48 h p.i., respectively). Co-injection with cold TSHR-Ab at doses ranging from 25 to 100 µg effectively reduced background signals, especially in spleen, liver, and bone. Notably, a dose of 25 µg cold TSHR-Ab reduced off-target signals without affecting tumor uptake. The biodistribution and IHC analyses further supported PET imaging findings. Conclusion TSHR-targeted radiotracer [64Cu]Cu-NOTA-TSHR-Ab was synthesized with high radiochemical purity. Our preclinical evaluation results demonstrate it is a promising radiotracer for PET imaging of TSHR-positive thyroid cancer, which may guide and monitor TSHR-targeted therapies. High radiotracer uptake in tumor, prolonged retention time, and favourable pharmacokinetics with the support of cold antibody co-injection, pave the way for the development of paired radiotherapeutics to treat TSHR-positive thyroid cancers.

Background/Objectives: Pneumonitis caused by radiotherapy for lung cancer may be missed since it often occurs only several months later. In a previous trial including patients of any age, a scoring system was tested to facilitate the correct diagnosis of radiation pneumonitis. Since elderly lung cancer patients have a greater risk of developing this complication, a separate scoring system for this group appears useful. Our prospective multi-center trial (NCT06480734) investigates a specific tool for elderly patients irradiated for lung cancer. Methods: Patients aged ≥65 years with lung cancer will complete paper-based questionnaires and rate symptoms potentially caused by pneumonitis weekly during and up to 24 weeks following radiotherapy. The total score of this symptom-based scoring system ranging from 0 to 9 points is correlated to pneumonitis. The discriminative power of the scoring system is evaluated by calculating the area under the receiver operating characteristic curve. Optimality is defined as a cut-off score with sensitivity ≥90% and specificity ≥80%. Moreover, the Youden index will be applied. Fifty-nine patients are required for the full analysis set. Assuming 5% will not qualify for this set, 65 patients should be enrolled. Moreover, patient satisfaction with the scoring system is evaluated. If the dissatisfaction rate is >20%, the system needs modifications; if the dissatisfaction rate is >40%, it is considered not useful. An optimal cut-off score facilitating the diagnosis of pneumonitis and its discrimination from other lung diseases will contribute to a corresponding mobile application to be used by elderly lung cancer patients at home.

Background: While the benefits of physical activity (PA) for cancer survivors are well-documented, there is limited research specifically exploring its effects on health-related quality of life (HRQoL) among testicular cancer (TC) survivors. This review aims to examine the available literature on the relationship between PA and HRQoL in TC survivors post-treatment. Objective: To identify and synthesize existing studies on the effects of PA on HRQoL outcomes in TC survivors. Eligibility criteria: Studies that examined the relationship between PA, TC survivorship, and HRQoL across various phases of survivorship were included. Only peer-reviewed articles and gray literature addressing these topics were considered. Sources of evidence: A systematic search was conducted across seven databases and gray literature. Articles were evaluated based on titles, abstracts, and full-text reviews for inclusion. Charting methods: Following Arksey and O’Malley’s scoping review framework and PRISMA-ScR guidelines, studies were charted for key findings regarding the effects of PA on cancer-related fatigue, psychosocial outcomes, and HRQoL in TC survivors. The search also focused on identifying barriers to PA adherence and gaps in the current literature. Results: Three studies were examined: one experimental study, one feasibility study, and one cross-sectional study. Findings suggested that PA interventions could reduce cancer-related fatigue, improve psychosocial well-being, and enhance HRQoL indicators such as vitality, self-esteem, and social functioning. High-intensity interval training showed short-term benefits, while low-intensity activities demonstrated feasibility for broader adoption. Adherence barriers included treatment side effects and psychosocial factors. Limitations included small sample sizes, self-reported data, and lack of long-term follow-up. Conclusion: The findings suggest that PA can improve HRQoL in TC survivors, but significant gaps remain, particularly in terms of longitudinal studies, diverse populations, and tailored interventions. Future research should focus on developing scalable, sustainable PA interventions that address adherence and long-term health outcomes for TC survivors.

AbstractBackgroundLGI1‐antibody encephalitis (LGI1‐Ab‐E) is a common form of autoimmune encephalitis where most patients demonstrate ‘good’ clinician‐rated outcomes. However, more targeted questionnaires reveal numerous debilitating symptoms for many years. To better quantify these persistent features, we designed the LGI1‐Antibody Encephalitis Rating (LANTERN) scale, a quantified, disease‐specific patient‐reported outcome measure (PROM), adhering to FDA guidelines.MethodsA participant‐driven mixed‐methods approach to develop a clinically valid questionnaire over three stages: (1) Item generation through semi‐structured interviews; (2) Repeated cognitive debriefing rounds to advance comprehensibility, relevance and comprehensiveness; (3) Psychometric survey to condense the most sensitive and valid questions. Analyses incorporated sensitivity testing with multiple internal and external validations.ResultsFrom 73 items across six domains (Stage 1; n = 18), a questionnaire assessing the frequency and severity of 43 symptoms (80 questions), plus nine activities of daily living (ADL), was developed through cognitive debriefing (Stage 2; n = 15). This 89‐question survey was completed (Stage 3; n = 66 patients and 32 relatives) and distilled, using exploratory factor analyses, to a three‐factor symptom‐burden questionnaire comprising 41 questions (19 symptoms and 6 ADL), separated into physical, cognitive/behavioural and ADL domains. These factors demonstrated strong internal reliability (Cronbach alpha: 0.85–0.91), correlations with relative‐completed questionnaires (R = 0.73–0.85; p < 0.001), good‐to‐excellent intraclass re‐testing correlations (0.81–0.98; n = 19) and strong associations with numerous predefined external measures.DiscussionLANTERN represents a PROM for LGI1‐Ab‐E, with initial content, structural and construct validity and test–retest reliability. It can be used as a reliable, tailored, efficient and sensitive method to establish symptom burden in people with LGI1‐Ab‐E, both in clinical practice and trials.

Data indicate that earlier initiation of anti-tumor necrosis factor alpha (anti-TNF-α) biologic medicines may prevent progression to irreversible bowel damage and improve outcomes for patients with inflammatory bowel disease (IBD), particularly Crohn’s disease. However, the high cost of such therapies may restrict access and prevent timely treatment of IBD. Biosimilar anti-TNF-α medicines may represent a valuable opportunity for cost savings and optimized patient outcomes by improving access to advanced therapies and allowing earlier anti-TNF-α treatment initiation. Biosimilar anti-TNF-α medicines have been shown to offer consistent therapeutic outcomes to their reference medicines, yet despite entering the IBD treatment armamentarium over 10 years ago, their implementation in clinical practice remains suboptimal. Factors limiting the ‘real’ use of biosimilar anti-TNF-α medicines may include an ongoing lack of understanding and acceptance of biosimilars by both healthcare professionals (HCPs) and patients, as well as systemic factors such as formulary decisions outside of the control of the prescriber. In this review, an expert panel of gastroenterologists discusses HCP-level considerations to improve biosimilar anti-TNF-α utilization in IBD in order to support early anti-TNF-α initiation and maximize patient outcomes.

Abstract INTRODUCTION Limited data exist on the utility of plasma biomarkers to predict incident abnormal amyloid positron emission tomography (PET). In this study we evaluate the association of plasma Alzheimer's disease (AD) biomarkers with amyloid PET progression among initially amyloid PET negative (A−) individuals. METHODS We included 290 A−, cognitively unimpaired Mayo Clinic Study of Aging participants. We estimated the association of each baseline plasma biomarker with progression from A− to A+ and with rate of amyloid PET change. RESULTS Interquartile range differences in amyloid beta 42/40, percent phosphorylated tau 217 (%p‐tau217), and Amyloid Probability Score 2 were associated with 1.29 ( P = 0.09), 1.38 ( P < 0.001), and 1.20 ( P = 0.05) increases, respectively, in the hazard of progression from A− to A+ and 0.27 ( P = 0.16), 0.50 ( P = 0.007), and 0.28 ( P = 0.15) Centiloid/year increases, respectively, in annual rate of amyloid PET change. DISCUSSION Plasma %p‐tau217 may be a useful screening tool to enrich for participants with increased likelihood of progressing from normal to abnormal amyloid PET in a primary prevention trial. Highlights Plasma phosphorylated tau 217 was associated with amyloid positron emission tomography progression, negative to positive. The associations were weaker for amyloid beta 42/40 and Amyloid Probability Score 2. Age and apolipoprotein E ε4 carriership were also important predictors. These markers may be useful for enrichment of a primary prevention trial.

AbstractBackgroundColon cancer patients have inferior overall survival than a matched general population (MGP). It is unknown if physical activity is associated with a reduction in this survival disparity.MethodsData were analyzed from two National Cancer Institute–sponsored postoperative treatment trials in stage III colon cancer, Cancer and Leukemia Group B (CALGB) 89803 and 80702, with 2876 patients who self‐reported physical activity. Physical activity was converted to metabolic equivalents (MET‐hours/week). The MGP was derived from the National Center for Health Statistics and matched on age, sex, and year.ResultsIn CALGB 89803, among patients who were alive at 3 years, those with <3.0 and ≥18.0 MET‐hours/week had subsequent 3‐year overall survival rates that were −17.1% (95% confidence interval [CI], −22.4 to −11.8) and −3.5% (95% CI, −7.7 to 0.3) lower than MGP, respectively. In CALGB 80702, among patients who were alive at 3 years, those with <3.0 and ≥18.0 MET‐hours/week had subsequent 3‐year overall survival rates that were −10.8% (95% CI, −15.4 to −6.9) and −4.4% (95% CI, −7.6 to −1.6) lower than MGP, respectively. In pooled analyses, among patients who were alive and did not have tumor recurrence by year 3 (n = 1908), those with <3.0 and ≥18.0 MET‐hours/week had subsequent 3‐year overall survival rates that were −3.1% (95% CI, −6.2 to −0.3) lower and 2.9% (95% CI, 1.5–4.2) higher than MGP, respectively.ConclusionsPhysical activity is associated with an attenuation of the survival disparity between patients with stage III colon cancer participating in clinical trials and MGP. Colon cancer survivors who are physically active may achieve survival that approximates the MGP.