Samsung Medical Center

To evaluate the malignancy risk of thyroid incidentalomas (TI) detected on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with cancer and identify factors guiding further evaluation. Among 71,878 patients who underwent 18F-FDG PET/CT between Jan 2019 and Dec 2022, 2185 patients (2202 nodules) received ultrasound for focal thyroid uptake. Final diagnoses were made for 233 patients (234 nodules). The maximum standardized uptake value (SUVmax) on PET, CT features, and cytologic or histopathological results were reviewed. Receiver operating characteristic curve analysis determined optimal thresholds for age, nodule size, and SUVmax. Logistic regression identified independent predictors of malignancy. The malignancy rate of PET/CT-detected TI was 50.4% (118/234). Malignant nodules were associated with younger age (p = 0.03), smaller size (p < 0.001), higher SUVmax (p < 0.001), homogeneous density (p = 0.03), and irregular CT margins (p < 0.001). In multivariable analysis, smaller size (< 1.5 cm; odds ratio [OR], 2.65; 95% CI: 1.45-4.85; p = 0.001), irregular CT margin (OR, 3.04; 95% CI: 1.62-5.70; p = 0.001), and higher SUVmax (≥ 6.25; OR, 2.55; 95% CI: 1.44-4.52; p = 0.001) remained independent predictors of malignancy. In our retrospective cohort, the risk of malignancy in TI detected on ¹⁸F-FDG PET/CT increases with smaller nodule size, higher SUVmax, irregular CT margins, and younger patient age. Combining these imaging and clinical parameters improves malignancy prediction. In oncologic patients, selective ultrasound evaluation of such nodules may facilitate diagnosis while avoiding unnecessary procedures. Question Which clinical and imaging features predict malignancy in TI detected by 18F-FDG PET/CT in cancer patients? Findings Malignancy was associated with smaller nodule size (< 1.5 cm), higher SUVmax (≥ 6.25), and irregular margins on CT among 234 cases. Clinical relevance Cancer patients with metabolically active thyroid nodules showing irregular CT margins may benefit from selective ultrasound to enable early diagnosis and appropriate management.

Amivantamab is an EGFR-MET bispecific antibody approved as an intravenous formulation for EGFR-mutated advanced non-small cell lung cancer (NSCLC). Intravenous delivery is frequently associated with infusion-related reaction (IRRs), which require adopting slow infusion rates and splitting the first dose over 2 days. The PALOMA study assessed the safety and feasibility of subcutaneous amivantamab administration and identified the formulation and recommended phase II doses (RP2Ds) for multiple dosing schedules. PALOMA is a phase Ib dose-escalation study in 158 participants with advanced solid malignancies. Primary objectives included pharmacokinetics, safety, and determining RP2Ds for every-2-week (Q2W), every-3-week (Q3W), and every-4-week (Q4W) administration. The safety profile of subcutaneous amivantamab was largely consistent with intravenous monotherapy; most common toxicities reflected on-target EGFR/MET inhibition. Subcutaneous amivantamab resulted in meaningfully shorter administration time (≤ 10 minutes vs. 2.3 hours for intravenous beyond cycle 3) and lower incidence and severity of IRRs versus historical intravenous data, which eliminates the need for split-dose administration. Pharmacokinetic analyses and population pharmacokinetic modeling/simulation were used to estimate subcutaneous amivantamab RP2Ds of 1600 mg (2240 mg, ≥ 80 kg), 2400 mg (3360 mg, ≥ 80 kg), and 3520 mg (4640 mg, ≥ 80 kg) for Q2W, Q3W, and Q4W schedules, respectively. The observed efficacy was consistent with intravenous amivantamab monotherapy. Subcutaneous amivantamab administration substantially reduced IRRs, obviating the need for prolonged infusions and 2-day split-dosing at first administration. The identified RP2Ds for subcutaneous amivantamab are implemented in ongoing studies evaluating amivantamab regimens in NSCLC, colorectal cancer, and head and neck squamous cell carcinoma.

Minimal residual disease (MRD) detection using liquid biopsy is an emerging tool for risk stratification and monitoring for recurrence in resected early stage NSCLC. There is increasing need for clear guidance on its optimal clinical implementation. The Asian Thoracic Oncology Research Group (ATORG) convened a multidisciplinary panel of 27 experts to develop a consensus statement on the clinical application of circulating tumor DNA-based MRD testing in early stage resected NSCLC, using a structured Delphi methodology. Statements were organized into the following broad thematic domains: assay validity and standardization; harmonization in research and trials; clinical application; challenges in implementation; consensus recommendations; infrastructure for regional MRD adoption; and roadmap for pragmatic trials. A total of 23 position statements were developed, of which all except one achieved strong consensus. The consensus highlighted the need to define minimum analytical performance thresholds for MRD assays, improve standardization of reporting metrics, and clear guidelines for pre-analytical handling. Harmonization of blood sampling time points and terminology across clinical trials is also essential to confirm the prognostic value of MRD assays. Although current MRD assays demonstrate high specificity and positive predictive value, variable sensitivity precludes routine use for adjuvant therapy de-escalation outside clinical trials. Broader access, sustainable funding, ongoing consensus building, and collaborative real-world data generation are also critical to support clinical implementation and adoption. Future clinical trials must account for the distinct biology and changing standards of care associated with different driver genes. These consensus recommendations provide a pragmatic framework to guide the responsible integration of MRD testing into clinical research and practice.

Background Chlorogenic acid (CGA) and taurine are well-known antioxidant compounds reported to reduce skin cellular senescence. However, the biological mechanisms underlying their skin-protective effects remain unclear. Methods In this study, we conducted transcriptome-wide RNA sequencing to profile gene expression changes in human epidermal keratinocytes, melanocytes, and fibroblasts following treatment with CGA, taurine, or their combination. To identify aging-related genes, we integrated evidence from aging databases, perceived-age GWAS, enrichment in aging-related gene ontology and pathways, and drug-gene interaction annotations. Validation of representative genes was performed using quantitative real-time PCR. Results A total of 197 differentially expressed genes (DEGs) were identified, of which 62 were prioritized as aging-related DEGs (AR-DEGs) based on their relevance to skin aging anti-senescence-associated pathways, highlighting regulatory transcription factors including TGFB2 , ETS1 , and EGR1 . Co-treatment enhanced the transcriptional effects of CGA and taurine, with several genes exhibiting synergistic responses. Targeted transcriptome-wide association analysis indicated potential links between specific AR-DEGs, such as FST, and phenotypes including perceived age and skin pigmentation. Conclusion By identifying key genes and pathways that contribute to cellular longevity in human skin, this study provides molecular insights for developing anti-aging strategies with potential applications in dermatology.

Metastasis-directed therapy (MDT) offers the potential to delay systemic treatment in oligometastatic renal cell carcinoma (OM-RCC); however, outcomes in clinical practice, particularly with repeat MDT in patients naïve to systemic therapy, are not well characterized. We analyzed 133 patients with OM-RCC who were naïve to systemic therapy (with up to five lesions) and treated with MDT: metastasectomy, stereotactic body radiotherapy, or radiofrequency ablation. In total, 38 patients underwent a second MDT for subsequent relapse without systemic therapy. Kaplan-Meier and Cox regression analyses evaluated progression-free survival (PFS), systemic therapy-free survival (STFS), and overall survival (OS). A time-varying Cox model accounted for intrapatient correlation when comparing PFS between MDT sessions. A two-factor risk score was constructed using disease-free interval (DFI < 1year) and metastatic burden (two or more lesions). With a median follow-up of 49.8months, 5-year STFS and OS were 44.9 and 85.0%, respectively. Two-year PFS was similar between the first (47.9%) and second MDT (39.9%, P = 0.996). After the first MDT, DFI < 1year and two or more lesions independently predicted inferior PFS, STFS, and OS. After the second MDT, only DFI < 1year remained significant for PFS. The composite risk score, assigning one point each for DFI < 1year and two or more lesions, effectively stratified outcomes, with 2year PFS rates of 63.6% (score 0), 33.5% (score 1), and 9.1% (score 2) after the first MDT. MDT provides durable disease control and defers systemic therapy in systemic therapy-naïve OM-RCC. Repeat MDT offers comparable outcomes to initial treatment in selected patients. A simple risk score integrating DFI and metastatic burden may guide patient selection and shared decision-making. In systemic therapy-naïve oligometastatic RCC, metastasis-directed therapy (MDT) provides durable systemic therapy-free and overall survival. Repeat MDT, when applied to carefully selected patients, achieves progression control comparable to that of the initial treatment. A simple two-factor risk score incorporating a disease-free interval of < 1year and ≥ 2 effectively stratifies patients into favorable and poor prognostic groups. This tool offers clinicians a practical means of triaging candidates, optimizing the timing of MDT, and determining when early systemic therapy should be considered.