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Phase II study of ceralasertib (ATR inhibitor) plus durvalumab in patients with advanced gastric cancer (AGC) who progressed on prior anti-PD-(L)1 therapy.
4062 Background: The standard first-line therapy for advanced gastric cancer (AGC) now includes immune checkpoint inhibitors (ICIs), but resistance is inevitable. ATR inhibition may sensitize tumors to ICIs by enhancing DNA damage and activating the cGAS-STING pathway. We evaluated the efficacy and immunologic impact of ceralasertib (ATRi) plus durvalumab in IO-pretreated AGC. Methods: This open-label phase II trial (NCT03780608) enrolled patients with metastatic gastric adenocarcinoma who progressed on prior anti-PD-(L)1 therapy. Patients received ceralasertib (240mg BID, Days 1–7) and durvalumab (1500mg IV, Day 8) every 28 days. The primary endpoint was ORR (RECIST v1.1). Serial endoscopic biopsies were collected at baseline (BL), post-ATRi monotherapy (FU1), and post-durvalumab combination (FU2) for multi-omics analysis (WES/WTS/scRNA-seq). Results: Thirty patients were enrolled (median 4 prior lines; all HER2-negative). ORR was 33.3% (10/30) and DCR was 56.7%. Median PFS was 4.3 months (95% CI, 1.45–7.10); median OS was not reached. Patients receiving study treatment immediately after prior IO failure had significantly longer PFS than those with intervening non-IO lines (p < 0.05). Grade 3 TRAEs occurred in 10% (3/30) of patients, with no new safety signals identified. Dose reductions of ceralasertib occurred in 4 patients. Multi-omics revealed that higher baseline scarHRD scores correlated with shorter PFS (p = 0.031). scRNA-seq showed that responders (R) had significant depletion of aneuploid clones post-treatment, whereas non-responders (NR) exhibited clonal persistence. Mechanistically, R showed baseline enrichment of the ATR-ATRIP axis, indicating functional dependency on replication stress tolerance. ATR inhibition in R induced replication fork collapse and ATM-CHEK2-mediated apoptosis. Conversely, NR displayed base excision repair deficiency signatures and adaptive G1-phase retention, facilitating evasion of ATRi-induced lethality. Conclusions: Ceralasertib plus durvalumab is efficacious and well-tolerated in IO-refractory AGC. The higher efficacy observed in patients treated immediately after prior IO failure suggests that ATR inhibition may effectively reverse acquired resistance to PD-1 blockade. This biomarker-driven approach warrants further validation in a larger cohort. Clinical trial information: NCT03780608 .
Importance of where you die: Lung cancer mortality trends in homeless-proxy settings across the U.S.
e13755 Background: Homelessness significantly impacts health, contributing to worse cancer outcomes and higher death rates. However, national cancer datasets usually don't include housing status. This study utilized location of death as a proxy for housing instability to assess demographic patterns and trends in lung cancer mortality among potentially homeless individuals in the United States. Methods: We conducted a retrospective population-level study using CDC WONDER Multiple Cause of Death data from 1999 to 2020, focusing on adults aged 25 and older. Lung cancer deaths were identified using the ICD-10 code C34. Deaths that occurred in "other," "public place," "dead on arrival," or "unknown" settings were considered deaths that indicated homelessness. We calculated age-adjusted and crude mortality rates, separating the data by race, sex, and age. We used linear regression to find trends over time. We used multivariable logistic regression to determine the odds of death in homeless-proxy settings, using American Indian/Alaska Native populations as a comparison group. The CDC WONDER database did not have information on late-stage cancer, which limited direct comparisons of cancer stages. Results: Among the 3.36 million lung cancer deaths, 59,680 (1.8%) were in homeless-proxy settings, a number that increased from 45.3% in 1999 to 66.7% in 2020 (p < 0.001). The largest group of deaths was in adults aged 45–64. Age-adjusted mortality rates in “other” settings were highest in White individuals (76.7/100,000), followed by Black (41.3/100,000) and Asian/Pacific Islander individuals (38.0/100,000). In regression models, odds of dying in homeless-proxy settings were highest in Black (OR 2.94, 95% CI 2.85–3.04), White (OR 2.51, 95% CI 2.43–2.59), and Asian/Pacific Islander (OR 1.84, 95% CI 1.72–1.96) individuals relative to American Indian/Alaska Natives. Although the total death rates were higher for Whites, the adjusted odds ratio shows the chances of dying in a homeless-proxy setting for each group, rather than overall population rates, which clarifies the seeming difference. Conclusions: Lung cancer mortality in potentially homeless individuals is rising, with significant racial disparities and a burden concentrated in middle-aged adults. Policy and care delivery frameworks must recognize housing instability as a critical component of cancer outcomes. Integrated oncology-housing interventions are urgently needed to reduce structural inequities and support at-risk populations.
Glucagon-like peptide-1 injectable medication uptake among United States cancer survivors with diabetes: National estimates and socioeconomic patterns from 2024.
e23094 Background: Use of glucagon-like peptide-1 (GLP-1) receptor agonists has expanded rapidly for diabetes and obesity management, but real-world uptake among cancer survivors, who often have high cardiometabolic risk, remains poorly characterized. We evaluated national prevalence and correlates of GLP-1 injectable medication use among United States (U.S.) cancer survivors with diabetes. Methods: We conducted a cross-sectional analysis of the 2024 National Health Interview Survey (NHIS) adult sample using IPUMS NHIS. Cancer survivorship was defined as a self-reported history of cancer. The primary cohort included adult cancer survivors with diabetes; a secondary cohort included survivors with diabetes or prediabetes. The outcome was self-reported use of GLP-1 injectable medication. We estimated survey-weighted prevalence overall and by insurance, poverty level (Federal Poverty Level [FPL] categories), and obesity status (Body mass index [BMI] ≥30 vs < 30). Adjusted prevalence ratios (aPR) were estimated using survey-weighted Poisson regression with log link, adjusting for insurance, poverty, obesity, age, sex, race/ethnicity, education, insulin use, diabetes pill use, and diabetes duration. Results: The primary cohort included 692 cancer survivors with diabetes (unweighted; GLP-1 users n = 148). The weighted prevalence of GLP-1 injectable use was 21.2% (95% confidence interval [CI] 17.3–25.0). Uptake varied by insurance (Private 25.5%, Medicare 17.6%, Medicaid 36.3%, Uninsured 28.9%, Other 11.0%) and poverty ( < 100% FPL 16.8% vs ≥400% FPL 25.0%). GLP-1 use was higher among survivors with obesity (BMI ≥30, 27.6% vs BMI < 30, 16.2%). In adjusted models, obesity (BMI ≥30) was independently associated with greater GLP-1 use (aPR 1.65, 95% CI 1.16–2.33, p = 0.005), as was higher income (≥400% FPL vs < 100% FPL: aPR 2.09, 95% CI 1.09–3.98, p = 0.026). In the secondary cohort of survivors with diabetes or prediabetes (n = 1273), weighted GLP-1 injectable use was 14.1% (95% CI 11.7–16.5). Conclusions: Approximately 1 in 5 U.S. cancer survivors with diabetes reported GLP-1 injectable use in 2024. Uptake was higher among survivors with obesity and higher socioeconomic status, suggesting potential access or prescribing disparities in this high-risk population. Future work should evaluate longitudinal patterns and cancer-type–specific differences as newer agents diffuse into routine survivorship care.
Neoadjuvant apatinib plus camrelizumab in renal cell carcinoma with inferior vena cava tumor thrombus: Results of a phase II study.
4536 Background: Renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVCTT) remains a surgically challenging condition, and evidence supporting neoadjuvant systemic therapy is still evolving. We conducted a phase II study to evaluate the efficacy and safety of apatinib combined with camrelizumab as neoadjuvant treatment in this population. Methods: This single-arm phase II trial enrolled patients with histologically confirmed, resectable RCC with IVCTT (cT3b-T4, N0-1, M0-1; ECOG performance status 0-1). Patients received camrelizumab 200 mg i.v. every 2 weeks for six cycles plus oral apatinib 250 mg once daily, followed by surgical resection when feasible. The primary endpoint was downgrading of Mayo level of tumor thrombus (TT). Secondary endpoints included TT response (RECIST 1.1), response of primary renal tumor, safety (CTCAE v5.0), progression-free survival, and overall survival. Results: Nine patients were included in the intention-to-treat analysis. TT response was observed in 4 patients (44.4%), with disease control achieved in 8 patients (88.9%); one patient (11.1%) experienced progression. Mayo level downgrading occurred in 3 patients (33.3%), all of whom subsequently underwent surgery. Overall, 7 of 9 patients (77.8%) successfully completed neoadjuvant therapy and underwent robotic-assisted radical nephrectomy with thrombectomy. For primary renal tumor, partial response was observed in 1 patient (11.1%), and stable disease in 8 patients (88.9%), resulting in a disease control rate of 100%. Treatment-related adverse events were manageable and consistent with known safety profiles, with grade ≥3 events including hypertension, proteinuria, pneumonitis, and immune-related myasthenia gravis. At a median follow-up of 45 weeks, survival outcomes remain immature. Conclusions: Neoadjuvant apatinib plus camrelizumab demonstrated promising antitumor activity and acceptable safety in patients with RCC and IVCTT, achieving meaningful TT response and Mayo level downgrading, thereby facilitating surgical resection. These findings support further investigation of neoadjuvant combination therapy in this high-risk population. Clinical trial information: ChiCTR2300069990. Patient baseline characteristics. Characteristic N=9 Median age, years, (IQR) 58 (54-66) Sex, n (%) Male 6 (67) Female 3 (33) ECOG PS, n (%) 0 7 (78) 1 2 (22) Clinical T stage, n (%) cT3b 2 (22) cT3c 3 (33) cT4 4 (44) Clinical N stage, n (%) cN0 3 (33) cN1 6 (67) Clinical M stage, n (%) cM0 3 (33) cM1 6 (67) Primary tumor size, cm (IQR) 12.4 (7.3-17.3) Length of the tumor thrombus, cm (IQR) 11.3 (7.2-13.8) Histological subtype on baseline biopsy, n (%) Clear cell RCC 8 (89) TFE3 translocation RCC 1 (11) Mayo level of TT at baseline I 0 II 4 (44) III 2 (22) IV 3 (33) IQR interquartile range, ECOG Eastern Cooperative Oncology Group, PS performance status, RCC renal cell carcinoma.
Demographic and socioeconomic patterns of malignant melanoma in junctional nevus: An NCDB analysis.
e21572 Background: Malignant melanoma in junctional nevus (MMJN) is a rare type of cutaneous melanoma that originates in melanocytes located at the dermoepidermal junction. Although uncommon, malignant transformation in a junctional nevus is aggressive, with documented cases progressing to parotid and cervical lymph nodes as well as distant sites. Nevus-associated melanomas, including those arising in junctional nevi, have shown better overall prognosis independent of sentinel lymph node status. Due to MMJN being grouped with broader melanoma categories, we conducted a large-scale analysis of the NCDB to clarify demographic and socioeconomic factors influencing diagnosis and outcomes. Methods: A retrospective cohort analysis using NCDB data (2004–2020) was performed to evaluate demographic and socioeconomic characteristics of patients with MMJN (ICD-O-3 code 8740/3). Variables included age, sex, race, Hispanic origin, income, insurance, facility type, region, tumor features, surgical procedures, primary site, treatment, and Charlson-Deyo comorbidity score. Incidence trends were analyzed using descriptive statistics. Results: A total of 612 patients were identified with a stable incident trend over the study period (R²=0.18). Most were male (56.7%), White (97.5%), and non-Hispanic (93.0%), and had a mean age at diagnosis of 56.14 years (SD=16.83). The largest proportion were treated at academic/research programs (43.7%), in the Pacific region (35.0%), and lived in metro areas ≥250k population (78.8%). Private insurance (66.3%) and Medicare (27.1%) were most common. Nearly half lived in the highest income quartile (49.2%), and the mean travel distance was 32.4 miles. The trunk (37.8%) and lower limb/shoulder (25.4%) were the most frequent anatomical sites. Most tumors were Stage 0 (23.5%) or Stage I (28.4%); Stage II–IV disease were rare. The mean tumor size was 18.37 mm. Most patients had a Charlson–Deyo score of 0 (91.2%). Survival beyond thirty days (98.8%) and ninety days (98.5%) was high. Wide local excision (26.3%) and wide excision with sentinel node biopsy (24.5%) were the most common procedures. Few received radiation (1.5%), chemotherapy (0.5%), or immunotherapy (0.8%). Survival rates were 96.5% at two years, 92.0% at five years, and 78.1% at ten years. Conclusions: To our knowledge, this is the first NCDB analysis focused on MMJN, addressing a major gap in the literature on this rare neoplasm. Consistent with prior case studies describing nevus-associated melanoma, most patients were non-Hispanic, White, and presented with early-stage disease. This study also provides the first large-scale evaluation of socioeconomic characteristics, showing that most lived in higher-income metro regions and received care at academic centers. Further research is needed to determine how these demographic and socioeconomic patterns impact detection, treatment decisions, and long-term survival.
Real-world efficacy and safety of photoimmunotherapy for recurrent nasopharyngeal carcinoma: A nationwide multicenter study in Japan.
6030 Background: Treatment options for locally recurrent or residual nasopharyngeal carcinoma (NPC) after definitive radiotherapy remain limited. Salvage surgery is often challenging due to anatomical constraints, while re-irradiation and systemic therapies provide modest efficacy with substantial toxicity. Photoimmunotherapy (PIT) is a light-activated anticancer treatment targeting epidermal growth factor receptor (EGFR) that has been approved in Japan since September 2020 for unresectable locally advanced or locally recurrent head and neck cancers. However, real-world clinical data on PIT for recurrent NPC are limited. We conducted the NPC-PIT Study, a nationwide observational study evaluating the real-world efficacy and safety of PIT in patients with recurrent NPC. Methods: Patients with recurrent or residual NPC treated with PIT were enrolled from 26 institutions. Patients with at least 3 months of follow-up after initial PIT were evaluated. Clinical characteristics, prior treatments, PIT illumination techniques, treatment response, overall survival, EBV-DNA levels, and treatment-related adverse events were analyzed. Results: As of November 2025, 46 patients were enrolled. The four cases with follow-up <2 months were excluded from the evaluation. The median follow-up duration was 18.6 months. Seventeen patients received one PIT cycle, 14 received two, 6 received three, and 5 received four sessions. Among the 42 evaluable patients, 29 (69.0%) achieved a complete response (CR) lasting ≥2 months. Twenty patients remain alive with no evidence of disease. Disease-related deaths occurred in 3 patients, and 2 patients died from carotid artery rupture after treatment. Grade ≥3 adverse events were observed in 9 patients (21.4%). The 1-year overall survival rate was 89.7%. Among cases where pre-treatment blood samples were collected, 80% (4/5) showed elevated EBV-DNA levels on Cycle 1 Day 7, suggesting that EBV-DNA levels may reflect biological changes associated with PIT treatment. Conclusions: In this nationwide real-world cohort, PIT provided meaningful and long-lasting local control with a manageable safety profile for recurrent NPC. These findings support PIT as a clinically meaningful local treatment option for recurrent NPC and warrant further optimization of patient selection and risk mitigation strategies.
IL7-IL15 fusion cytokine (fusokine)–secreting iPSC-derived mesenchymal stromal cells to convert immunosuppressive into highly immune-activated tumor microenvironments (TMEs), potentiate antitumor immunity, and synergize with PD-1 inhibition in ovarian cancer.
e14522 Background: Mesenchymal stromal cells (MSCs) exhibit inherent tumor-homing properties and can be programmed to produce therapeutic proteins in situ (Andreeff M.Cancer Res. 2002, JNCI 2004, ASCO 2018). Methods: Here we reprogrammed adult dermal fibroblasts into induced pluripotent stem cells (iPSCs) using a synthetic, non-integrating mRNA transfection system. These iPSCs were stably modified to express interleukin-7 and interleukin-15 as fusion construct, prior to mesodermal lineage specification into MSCs (hereafter referred to as IL7-IL15-iMSCs). Results: Functionally, IL7-IL15-iMSCs secreted supraphysiologic levels of cytokines and induced potent CD8 and CD4 T cell activation (incl. CD25,pAKT,pS6, pSTAT5) and proliferation sustaining the long-term expansion of T cells in vitro and of macrophages in vivo, thus converting immune-suppressive MSCs into immune-activating cells. IL7/IL15-modified iMSCs induced ID8 tumor cell death in vitro in triple co-culture systems comprising iMSCs, and human PBMCs. In a syngeneic mouse model of ovarian cancer (ID8 and platinum-resistant ID8 cells in C57BL/6 mice), intraperitoneal administration of IL7-IL15-MSCs resulted in reduced tumor burden and extended survival of 58%. Immunohistochemical and CyTOF analyses revealed massive infiltration of activated T cells, macrophages, and other immune cells into the tumor microenvironment (TME) as well as enrichment of tumoricidal M1-type macrophages, with no detection of regulatory T cells, in contrast to controls. Remarkably, the combination of IL7-IL15 iMSCs combined with PD1 mAB in the ID8-Luc-Ova model resulted in 100% survival with no detectable tumor by BLI on day 160, relative to a median survival of 66 days in untreated controls, 75 days in IL7/IL15 iMSCs treated mice, 139 days inPD1 mAB. Intra-venously (IV) injected MSC in the orthotopic 4T1 triple-negative breast cancer model, six weeks post IL7-IL15-iMSC IV administration, showed robust iMSC engraftment in the TME, infiltration of immune cells and tumor reduction. Hence, IV injected iMSC also home to tumors. Conclusions: These data establish IL7/IL15-iMSCs as a novel, immunologically active stromal cell platform capable of remodeling the TME and amplifying both innate and adaptive anti-tumor responses. IL7-IL15 iMSC convert an immune-suppressive into an highly immune-activated TME in diverse tumor types. Combination of IL7/IL15 iMSC with PD1 mAB resulted in apparent cures in the ID8 ovarian cancer model. The scalability of iPSC-derived MSCs, combined with synthetic mRNA reprogramming and stable cytokine expression, renders this platform well-suited for clinical translation and a first clinical trial in ovarian cancer is under development.
Clinicopathological features and prognosis analysis of 11 patients with TFE3-rearranged perivascular epithelioid cell tumors.
e23551 Background: To explore the clinicopathological features and prognostic analysis of TFE3 -rearranged PEComas. Methods: FISH data from PEComas patients diagnosed with TFE3 gene disruption between January 2014 and October 2024 were collected. The clinical features and pathology of the patients were analyzed. Results: A total of 11 patients with confirmed TFE3 rearrangement detected by FISH were included in the study, including 7 females and 4 males aged 25-70 years at diagnosis. The primary tumor sites were as follows: the retroperitoneum and abdominal cavity, kidney, transverse colon, urachal duct, uterus, and left lung. The maximum diameter of the tumor was 18 cm, the minimum diameter was 0.5 cm (accidentally discovered during other surgeries), the median value was 6 cm, and the mean value was 8.46 cm. The imaging manifestations of TFE3 -rearranged PEComas vary depending on the location and size of the tumor. RNA sequencing was performed on samples from 4 patients, revealing that 2 patients had SFPQ::TFE3 fusion, 1 patient had ASPSCR1::TFE3 fusion, and 1 patient had no known gene fusions. As of December 31, 2024, 2 patients were lost to follow-up after diagnosis, and among the 9 patients followed up, the median follow-up time was 31 months (4-139). With regard to treatment, all nine patients who completed follow-up underwent resection of the primary tumor. During follow-up, 6 patients achieved disease-free survival (4-94 months). Patient 1 developed liver metastasis 80 months after surgery. After that, the patient received surgical treatment for the liver metastasis. When the disease progressed, the patient was treated with everolimus. Patient 3 was diagnosed with lung metastasis following surgery for a renal lesion and did not undergo any further treatment. Patient 4 had multiple recurrences and underwent 4 surgeries. She successively received treatments of apatinib, everolimus, anlotinib combined with tislelizumab. She died 34 months after diagnosis. Conclusions: TFE3 -rearranged PEComas have unique clinicopathological features, with the majority of primary lesions occurring inside the abdominal cavity. After TFE3 rearrangement, PEComas are highly invasive, with potential for recurrence and metastasis, and the overall disease progression is relatively slow. At present, the primary treatment is surgery, and pharmacotherapy can increase the survival time of some patients. This study provides new clinical and molecular insights into TFE3 rearrangement in PEComa, emphasizing its significant role in the development of PEComa. It supports TFE3 rearrangement as a poor prognostic biomarker for PEComa and offers potential targets for the development of new therapeutic strategies. Future research is needed to further explore the molecular mechanisms of TFE3 rearrangement and to assess the efficacy of new treatment strategies.
Comparative outcomes of FLAG-based versus standard 3+7 induction therapy in adults with newly diagnosed acute myeloid leukemia: A systematic review and meta-analysis.
e18518 Background: Standard induction therapy for fit adults with newly diagnosed acute myeloid leukemia (AML) remains daunorubicin–cytarabine (3+7). FLAG-based regimens are increasingly used in high-risk AML, but their comparative efficacy and safety in the frontline setting remain uncertain. We performed a systematic review and meta-analysis to compare FLAG-based induction with standard 3+7 in newly diagnosed AML. Methods: A PRISMA 2020–compliant systematic review was conducted across PubMed, Embase, Cochrane Library, and Web of Science from inception through September 2025. Comparative studies evaluating FLAG or FLAG-IDA versus standard 3+7 induction in adults with newly diagnosed AML were included. Pooled odds ratios (ORs) were calculated using random-effects models. Outcomes included overall response rate (ORR), early mortality (30–60 days), survival outcomes, and treatment-related toxicity. Results: Five retrospective, double-arm cohort studies comprising 534 patients were included (322 FLAG-based; 212 standard 3+7). FLAG-based induction was associated with a significantly higher ORR compared with 3+7 (OR 1.83, 95% CI 1.03–3.22; I² = 34%). There were no significant differences in 30-day (OR 0.56, 95% CI 0.12–2.69) or 60-day mortality (OR 0.79, 95% CI 0.29–2.14). Overall survival outcomes were heterogeneous and could not be pooled; individual studies reported mixed survival results, with benefit observed in selected high-risk cohorts. FLAG-based induction was not associated with increased infectious complications, bacteremia, ICU admission, or prolonged hospitalization compared with standard induction. Patients receiving FLAG were more likely to proceed to consolidation therapy, while rates of allogeneic transplantation were similar between groups. Conclusions: FLAG-based induction therapy improves response rates compared with standard 3+7 in adults with newly diagnosed AML without increasing early mortality or major toxicity. However, survival benefits remain inconsistent and appear influenced by patient selection and post-remission strategies. Prospective randomized trials are required to define the optimal role of FLAG-based induction in contemporary AML treatment algorithms.
Neuropsychiatric symptom and biomarker changes with electroacupuncture in adolescent and young adult (AYA) cancer survivors: Results from a randomized controlled trial.
10054 Background: Electroacupuncture (EA) shows promise for managing neuropsychiatric symptoms, yet its role in adolescent and young adult (AYA) cancer survivors remains unclear. We conducted a randomized, controlled, patient- and assessor-blinded pilot trial comparing two EA regimens to evaluate effects on neuropsychiatric symptoms and associated biomarkers in AYA cancer survivors (ClinicalTrials.gov: NCT05283577). Methods: AYA cancer survivors aged 16–39 years who self-reported cognitive impairment, fatigue, insomnia, or psychological distress were randomized (1:1) to receive ten weekly EA sessions targeting either neuropsychiatric-specific acupoints (nEA) or non-neuropsychiatric-specific acupoints (sham EA; sEA). Blood collection, neurocognitive testing (CANTAB), and patient-reported outcomes (FACT-Cog, MFSI-SF, EORTC QLQ-C30) were obtained at four timepoints. Sixteen plasma cytokines were measured using ProcartaPlex immunoassays, and brain-derived neurotrophic factor (BDNF) concentrations were quantified using ELISA. Between-group effects were evaluated with linear mixed models and expressed as Cohen's d (positive values favor nEA). Adverse events (AEs) were graded using CTCAE v5.0. Results: Thirty-four AYAs participated (mean age 20.9 ± 3.5 years; 59% Hispanic/Latino; 59% hematologic and 21% CNS cancers). Most (82%) reported ≥2 neuropsychiatric symptoms at baseline. Completion of all EA sessions was comparable between study arms (nEA: 64.7%; sEA: 70.6%). A positive dose-response relationship was observed, with approximately half reporting at least one improved symptom after 5 weeks of treatment (nEA: 53.8%; sEA: 60.0%) and >80% reporting improvement at 4 weeks post-treatment (nEA: 80.0%; sEA: 92.3%). At 4-week follow-up, greater improvement in self-reported cognitive function favored sEA ( d = −1.017, p < 0.05), accompanied by between-group differences in BDNF ( d = −1.073, p < 0.05), IL-10 ( d = 1.378, p < 0.05), and RANTES ( d = 1.058, p < 0.05). All AEs were grade ≤ 2; tremors and pain were the most commonly reported. Conclusions: AYAs across both EA regimens demonstrated meaningful improvements in neuropsychiatric symptoms, accompanied by corresponding biomarker changes. However, maximal benefit occurred among participants who completed all scheduled sessions, underscoring the importance of strategies to optimize EA session adherence in this population. These findings support the feasibility of EA in AYAs and inform the design of larger trials. Clinical trial information: NCT05283577 .
An academic multimodal ctDNA strategy for minimal residual disease detection and therapy monitoring in advanced epithelial ovarian cancer: Insights from the phase IV IOLANTHE trial.
e17547 Background: Sensitive detection of minimal residual disease (MRD) and longitudinal monitoring of treatment response remain critical unmet needs in advanced epithelial ovarian cancer (EOC). ALMA (Agnostic Liquid Biopsy Multi-modal Advancement) is a tumor-agnostic circulating cell-free DNA (cfDNA) platform that integrates multiple orthogonal features—tumor fraction (TF), fragmentomic profile, methylation patterns, and somatic copy number alterations (SCNAs)—to improve MRD detection and disease monitoring. Here, we assessed the clinical feasibility of ALMA in patients with advanced EOC who underwent cytoreductive surgery and were treated with platinum-based chemotherapy plus bevacizumab, with or without olaparib as maintenance therapy within the phase IV IOLANTHE trial (NCT06121401). Methods: Plasma samples were prospectively collected at predefined longitudinal time points. Baseline samples were obtained from all patients prior to any surgical intervention or chemotherapy. A second time point was collected following surgery, either primary debulking (PD) or interval debulking (ID). Additional samples were collected at the end of chemotherapy and at 12 weeks after initiation of maintenance therapy. Whole-genome cfDNA sequencing was performed using a dual strategy: low-pass WGS for TF estimation, fragmentomic profiling, and SCNA detection, and bisulfite-free methylation sequencing (cf-MBD-seq) for genome-wide methylation analysis. To date, the enrollment of IOLANTHE trial has been completed, and 192 patients were included. Results: A total of 55 longitudinal plasma samples were analyzed from 32 patients. Following size-based ctDNA enrichment, TF detection was achieved in 100% of analyzed samples. Mean TF decreased longitudinally from 17.28% at baseline (n=25), to 6.31% after PD or ID surgery (n=19), 5.08% at completion of chemotherapy (n=8), and 3.80% at 12 weeks of maintenance therapy (n=3). Genome-wide methylation profiling identified 2857 differentially methylated regions (adjusted p<0.01), of which 68% were located within CpG islands, predominantly in promoter regions. Conclusions: The ALMA approach proved to be feasible. Analyses of further cases are in progress and the results are expected to be presented at the meeting. Clinical trial information: NCT06121401 .
Clinical benefit of oral selective estrogen receptor degraders in <i>ESR1</i> -mutant, HR-positive, HER2-negative advanced breast cancer: A systematic review and meta-analysis.
e13058 Background: ESR1 mutations are a key mechanism of acquired endocrine resistance in hormone receptor-positive, HER2-negative advanced breast cancer (ABC). Next-generation oral selective estrogen receptor degraders (SERDs) were developed to suppress mutant estrogen receptor signaling more effectively. Individual randomized trials have yielded heterogeneous results. We conducted a systematic review and meta-analysis to quantify the clinical benefits of oral SERDs, with a particular emphasis on the ESR1-mutant population. Methods: Phase II–III randomized trials comparing oral SERD monotherapy versus standard endocrine therapy (ET) in HR-positive, HER2-negative ABC after prior endocrine therapy were identified through systematic searches of PubMed, Embase, and CENTRAL through October 2025. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), grade ≥3 treatment-related adverse events, and overall survival (OS). Random-effects models with Hartung-Knapp adjustment were used. Results: Six randomized trials including 2,808 patients were analyzed. In the overall population, oral SERDs improved PFS versus standard ET (HR 0.82; 95% CI 0.72–0.93; I² 9.5%). In patients with ESR1-mutant tumors, oral SERDs demonstrated a pronounced PFS benefit (HR 0.58; 95% CI 0.39–0.87; I² 50%) and a significant OS improvement (HR 0.57; 95% CI 0.36–0.89; I² 0%). In contrast, no PFS benefit was observed in ESR1 wild-type disease (HR 0.93; 95% CI 0.77–1.13). Among ESR1-mutant patients, consistent PFS benefit was observed across clinically high-risk subgroups, including visceral metastases (HR 0.70; 95% CI 0.51–0.96), liver metastases (HR 0.55; 95% CI 0.34–0.88), prior fulvestrant exposure (HR 0.66; 95% CI 0.56–0.79), and ≥2 prior lines of therapy (HR 0.70; 95% CI 0.51–0.96). ORR was higher with oral SERDs in the overall population (OR 1.67; 95% CI 1.23–2.28). Oral SERDs increased rates of low-grade gastrointestinal adverse events, including diarrhea and nausea, without excess grade ≥3 toxicity. Conclusions: Oral SERDs provide clinically meaningful improvements in PFS and OS predominantly in patients with ESR1-mutant HR-positive, HER2-negative ABC, supporting ESR1 mutation status as a predictive biomarker for therapeutic selection. These findings reinforce a biomarker-driven approach to post-endocrine treatment sequencing.
Real-world outcomes of first-line pembrolizumab plus chemotherapy in metastatic triple-negative breast cancer with central nervous system metastases: A multicenter cohort from Poland, the Czech Republic, and Slovakia.
e13120 Background: Patients with metastatic triple-negative breast cancer (mTNBC) and central nervous system (CNS) metastases have an exceptionally poor prognosis and very short survival. In the KEYNOTE-355 trial, pembrolizumab in combination with chemotherapy demonstrated a survival benefit in patients with programmed death-ligand 1 (PD-L1) positive (combined positive score [CPS]≥10) mTNBC. Although patients with previously treated and stable CNS metastases were eligible (3% of the intention-to-treat population), efficacy outcomes for this subgroup have not been reported to date. Real-world evidence regarding the effectiveness of pembrolizumab-based chemotherapy in patients with mTNBC and CNS metastases remains limited. Methods: The CEBCC-101 real-world retrospective study evaluated the effectiveness of first-line pembrolizumab plus chemotherapy in patients with PD-L1–positive mTNBC across 20 oncology centers in Poland, the Czech Republic and Slovakia. Among 178 treated women, 14 (7.7%) had brain metastases at treatment initiation, all of which were stable following prior local therapy. Median overall survival (mOS) and progression-free survival (mPFS) were estimated using the Kaplan–Meier method with follow-up summarized descriptively. Results: The median age at initiation of systemic treatment was 52.5 years (IQR 44–67). Up to four metastatic lesions were identified in nine patients (64.3%), while the remaining patients (n = 5, 35.7%) presented with a higher intracranial tumor burden. The median diameter of the largest intracranial metastatic lesion was 20 mm (n = 11; IQR 13-28; range 5-36). All patients received radiotherapy as part of local treatment for brain metastases. Radiotherapy alone was administered in 10 patients (71.4%), while surgery followed by radiotherapy was performed in the remaining four cases (28.6%). Median follow-up was 10.2 months (Q1-Q3, 8.34-14.81; range 0.66–20.8). A total of 10 OS events and 13 PFS events were observed. The median OS was 10.4 months; OS rates at 3, 6, 9, 12, 15 and 18 months were 85.7%, 78.6%, 64.3%, 49%, 39.2% and 13.1%, respectively. The median PFS was 6.7 months; PFS rates at 3, 6, 9, and 12 months were 78.6%, 57.1%, 35.7%, and 7.1%, respectively. Conclusions: Patients with CNS metastases are more frequently encountered in real-world clinical practice than in clinical trial populations. In this multicenter real-world cohort of mTNBC with CNS metastases treated with first-line pembrolizumab plus chemotherapy, mOS and mPFS were markedly shorter than those reported for the overall population in the KEYNOTE-355 trial. These findings underscore the persistent unmet clinical need in mTNBC with CNS involvement and support further prospective evaluation and optimization of multimodal treatment strategies in this population.
Trends of occupational cancer notification in Brazil (2010-2024): A 15-year national database analysis.
e23354 Background: Occupational cancer is a significant yet under-recognized public health issue. While work-related exposures account for approximately 2-8% of all cancer cases in some developed countries, the real incidence in many low- and middle-income countries remains unknown. This study aims to evaluate the reporting frequency and the epidemiological profile of occupational cancer notifications in Brazil. Methods: We conducted a retrospective, national observational study using the Brazilian Notifiable Diseases Information System (SINAN), the official national database for mandatory notification of occupational cancer. Eligibility criteria included all cancer cases officially registered as work-related, from 2010 to 2024. Variables included patient demographics, work-exposure agents, and primary site of cancer, which were analyzed across three 5-year periods. The primary objective was to evaluate the absolute frequency and temporal trends of occupational cancer notifications over the 15-year period. Results: From 2010 to 2024, a total of 7,364 occupational cancer cases were registered. Notifications increased significantly over time, from 540 (2010-2014) to 4,993 (2020-2024). Most patients were male (69.2%), white (68.0%), and aged 50-79 years (73.1%), with 38% being current or former smokers. Skin cancer was the most prevalent cancer diagnosis (38.7%), with non-ionizing radiation being the leading work-exposure identified (34.6%). Other frequent sites included gastrointestinal (9.0%), genitourinary (7.3%), and lung (5.9%). Furthermore, work-exposure agents also included hydrocarbons (8.6%), benzene (7.4%), free silica (6.5%), ionizing radiation (5.7%), and asbestos (5.5%). Conclusions: A significant increase in occupational cancer notifications has been observed in Brazil, suggesting progressive improvement in system sensitivity. Skin cancer was the most frequent work-related cancer registered, with non-ionizing radiation being the major occupational exposure. Findings should be interpreted in light of potential underreporting, highlighting the need for further public policies to continuously improve the quality of national health registries and, ultimately, to ensure effective health prevention strategies for workers. Notifications of occupational cancer in Brazil by site and occupational exposure (2010-2024). Category Variables (n) 2010-2014 2015-2019 2020-2024 Total Overall Notifications 540 1,831 4,993 7,364 Cancer site Skin 294 652 1,907 2,853 Gastrointestinal 27 221 411 659 Genitourinary 12 188 338 538 Lung 25 87 319 431 Exposure Non-ionizing radiation 270 450 1,828 2,548 Hydrocarbons 49 152 430 631 Benzene 33 112 399 544 Free silica 33 112 332 477
Trends and patterns of lung cancer among psychoactive substance–using older adults in the United States 1999-2024: A CDC WONDER analysis.
e20086 Background: Lung cancer remains a leading cause of cancer-related morbidity and mortality in the United States. Cigarette smoking accounts for approximately 80-90% of lung cancer deaths and increases lung cancer risk by 15 to 30 fold compared to never smoking. Growing evidence suggests that other inhaled psychoactive substances may significantly increase the risk of lung cancer. Psychoactive substance use usually co-occurs with tobacco use. Methods: Using the CDC WONDER multiple cause of death (MCOD) database, we reviewed death certificates from 1999 to 2024 to assess lung cancer mortality trends among psychoactive substance-using older adults (≥ 65 years) in the US. We report age-adjusted mortality rates (AAMRs) per 100,000 persons, along with the average annual percent change (AAPC) and annual percent change (APC) using Joinpoint regression. Results: Over the study period, 1,015,383 lung cancer-associated psychoactive substance use deaths were recorded. The AAMR rose from 11.8 in 1999 to 80.7 in 2024, with an AAPC of 8.61 (95 % CI: 6.56 to 10.69). Overall, males had higher AAMRs than females, with a value of 8.6 in 1999, which rose to 99.5 in 2024. NH White individuals had the highest AAMR compared to all other races, rising from 12.0 in 1999 to 92.8 in 2024. The most common place of death was the decedent's home, accounting for 43.6% of the total deaths. Non-metropolitan areas had higher AAMRs compared to metropolitan areas, rising from 14.4 in 1999 to 132.5 in 2020. Regionally, the Midwest recorded the highest overall AAMRs, which increased from 10.9 in 1999 to 118.4 in 2024. States in the top 90th percentile reported AAMRs 20 times higher than those in the bottom 10th percentile. Conclusions: Lung cancer mortality among adults using psychoactive substances in the US is increasing and shows significant demographic and geographic disparities, highlighting the need for integrated prevention efforts. Future research should investigate the independent and combined effects of specific psychoactive substances on lung cancer risk to assess the precision of mortality data.
Survival outcomes with first-line platinum–etoposide plus durvalumab versus platinum–etoposide alone in extensive-stage small cell lung cancer with metastatic disease including brain metastases: A real world analysis.
e20138 Background: Patients with extensive-stage small cell lung cancer (ES-SCLC) frequently present with metastatic disease, including brain metastases, and have poor survival outcomes. Immune checkpoint inhibitors combined with platinum–etoposide chemotherapy are widely used. However, real-world data on how well they work in patients with central nervous system involvement and other metastatic sites is still limited. We compared survival outcomes associated with first-line platinum–etoposide with versus without durvalumab in a large real-world ES-SCLC population with metastatic disease, including brain metastases. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adult patients (≥18 years) with documented ES-SCLC and metastatic disease, including brain and extracranial metastases, who initiated first-line platinum–etoposide chemotherapy between March 2018 and January 2025 were identified. They were then stratified based on whether they received durvalumab. In order to balance baseline demographics and clinical comorbidities, a 1:1 nearest-neighbor propensity score-matching approach was used. Overall survival (OS) was the primary endpoint, and survival was estimated using the Kaplan–Meier method, while hazard ratios (HRs) were derived from Cox proportional hazards models. Results: Among 19,322 eligible patients, 1,087 received platinum–etoposide plus durvalumab while 18,235 received platinum–etoposide alone. Post propensity score matching, 1,087 patients were included in each cohort with well-balanced baseline characteristics (standardized differences < 0.1). Median OS was significantly longer in the durvalumab cohort than in the chemotherapy-alone cohort (643 vs 406 days). Survival probability at the end of follow-up was 34.4% versus 24.1%, respectively. Durvalumab-based therapy was associated with a significantly lower risk of death (HR 0.71; 95% CI 0.63–0.80; log-rank p < 0.001). Conclusions: In this comprehensive real-world analysis of ES-SCLC with advanced metastatic disease, including brain metastases, first–line platinum–etoposide plus durvalumab was associated with markedly improved overall survival compared with platinum–etoposide alone. These outcomes support the effectiveness of durvalumab-based chemo-immunotherapy in routine clinical practice among high-risk ES-SCLC populations.
Circulating heat shock protein 90 alpha (Hsp90α) as a biomarker for cancer cachexia.
12042 Background: Cancer cachexia is defined clinically by a consensus definition of ≥5% unintentional weight loss in cancer patients over previous 6 months. There is a need to develop blood-based biomarkers for more accurately identifying patients with cancer cachexia. Tumor-cell derived Hsp90α has been shown to be a key driver for muscle wasting and systemic inflammation in pre-clinical models of cancer cachexia. Methods: We conducted a prospective case control study between April 2020 and February 2025 to identify biomarkers of cancer cachexia. Cases were newly diagnosed patients with stage III/IV cancers with ≥5% unintentional weight loss and serum albumin of < 3.5g/dl (Cachexia group). Controls were newly diagnosed patients with stage I-III cancers without weight loss and serum albumin of ≥3.5g/dl (non- cachexia group). We collected 5ml of blood at first visit and analyzed plasma Hsp90α levels using Enzyme linked immunosorbent assay (ELISA). We performed univariable comparisons of geometric means of Hsp90α between the groups using two sample t-test . To evaluate the classification performance of Hsp90α for identifying cancer cachexia, we used receiver operating characteristic (ROC) analysis with area under the curve (AUC). Results: A total of 200 patients were consented and 171 were included in final analysis. There were 110 cases and 61 controls. Mean age of cases was 68 years and of controls 62 years (p=0.003). 64% of cases were males as opposed to 30% in controls (p <0.001). There was no significant difference in race between the groups. Cancer types included lung, gastro-intestinal, breast and other cancers in both cases and controls. Mean plasma Hsp90α at diagnosis was significantly higher in cases 40.60 ng/mL than in controls 32.47 ng/mL (p < 0.001). On up to one year follow up (6 visits total) the mean Hsp90α remained significantly elevated in cases as compared to controls (p <0.001). Mean Hsp90α levels among cases was highest in patients with GI cancers (49.98 ng/mL) followed by Lung cancer (40.67 ng/mL) and other cancer types (27.92 ng/mL), p <0.001. Based on ROC analysis, Hsp90α level of ≥35 ng/mL has AUC of 94% for differentiating cancer patient with cachexia from those without cachexia. When stratified by sex, Hsp90α ≥35 ng/mL remained significantly higher in cases than in controls for both men and women (p<0.001). Conclusions: Hsp90α is a blood-based biomarker that is significantly elevated in cancer patients with cachexia as opposed to those without cachexia. Plasma Hsp90α ≥35 ng/mL accurately identifies cancer patients with cachexia and represents a promising biomarker for cancer cachexia both in clinical care and research. Distribution of Hsp90α amongst case-control based on optimal cutoff (≥35 ng/mL). Variable Study group Cutoff category Number of patients Hsp90 Case < 35 20 Hsp90 Case ≥ 35 90 Hsp90 Control < 35 61 Hsp90 Control ≥ 35 0
SEZanne: A phase 2 randomized, open-label, multicenter study to evaluate the optimal dose, safety, and efficacy of ABBV-706 in combination with atezolizumab (atezo) versus standard of care (SOC) in patients (pts) with previously untreated extensive-stage (ES) small cell lung cancer (SCLC).
TPS8135 Background: SCLC is a neuroendocrine tumor accounting for ~15% of lung cancers, with a 5-year survival rate of ~7%. Platinum-based chemotherapy (PCT) remains the 1L SOC, achieving response rates of 60–70% in pts with ES-SCLC, though durable responses are rare. Adding a PD-L1 inhibitor (atezo or durvalumab) to PCT only modestly improves survival, and novel therapies are needed. Seizure-related homolog 6 (SEZ6), a neuroendocrine lineage marker highly expressed in SCLC, represents a promising target. ABBV-706, a SEZ6-directed antibody-drug conjugate with a topoisomerase 1 inhibitor payload, has shown promise as monotherapy in pts with relapsed SCLC, with an ORR of 57.3% (Byers et al. J Thorac Oncol. 2025;10:S23). The phase 2 SEZanne study (NCT07155174) evaluates the dose optimization, safety, and efficacy of ABBV-706 + atezo as a 1L regimen vs SOC. Methods: This global, open-label, randomized phase 2 study (~75 sites; up to 180 pts) compares ABBV-706 + atezo vs SOC. Eligible pts (≥18 years) have ES-SCLC requiring 1L therapy, ECOG 0–1, measurable disease per RECIST v1.1, and are candidates for PCT. Primary objectives are to evaluate safety/tolerability, identify the recommended phase 3 dose, and assess PFS of ABBV-706 in combination with atezo. Secondary objectives are to further evaluate efficacy (ORR, DOR, DCR, OS) and characterize the PK/immunogenicity of the combination. The study consists of 2 parts: a safety lead-in (~30 pts) and a dose optimization (~150 pts) stage. During safety lead-in, pts are randomized 1:1:1 to 2 doses of ABBV-706 Q3W + atezo or SOC. SOC includes 4 cycles of PCT (carboplatin) + etoposide + atezo followed by atezo maintenance; lurbinectedin may also be used in maintenance where locally approved. After the safety lead-in, additional pts will be randomized to the ABBV-706 + atezo arms that were deemed safe, or the SOC arm. Treatment continues until progression, intolerable toxicity, or other discontinuation criteria are met. The study is enrolling. Clinical trial information: NCT07155174 .
Sex-dependent features of primary non-small cell lung cancer course in patients with previous COVID-19.
e20044 Background: According to global statistics, women generally experience a milder response to COVID-19 than men, and moderate relative lymphocytosis, as opposed to relative lymphopenia, is considered a favorable prognostic indicator for this disease. However, the specific features of the malignant process in patients with non-small cell lung cancer (NSCLC) of both sexes who have recovered from COVID-19 hasn´t been sufficiently studied. The aim of the research was to investigate the characteristics of the course of primary NSCLC in patients of different sexes who had COVID-19. Methods: Conventional clinical and laboratory indicators were studied in patients with stage I-III non-small cell lung cancer, men and women aged 36-75 years. The main groups consisted of 32 men and 16 women whose COVID-19 was confirmed by real-time PCR 2-9 months before hospitalization. Control groups involved of 27 men and 16 women of the same age. Cases of NSCLC progression and mortality during the first year after surgery and chemoradiation therapy were recording. The Mann-Whitney U test and Student's t-test were used in the statistical analysis of the results. Results: In almost all patients in the main groups, tumors were detected during chest X-ray examination related to COVID-19 diagnosis. In men with previous COVID-19, contradictory changes were noted: a 2.7-fold increase (p < 0.05) in the incidence of early-stage NSCLC (st. IA, B) with a simultaneous trend towards an increase in the incidence of metastasis and mortality within a year after in-hospital treatment compared with the control group (p < 0.1). Besides, in men who died within the first year after the end of antitumor treatment, the relative lymphocyte counts before the treatment corresponded to the upper limit of normal or moderate lymphocytosis (28-45%) 4 times more often than in those who died in the control group (who more often had lymphopenia, p < 0.01). Women with previous COVID-19 showed clear signs of worsening disease curse and reduced treatment effectiveness (p < 0.05-0.01) with tumor prevalence similar to that observed in the control group. No association between 1-year survival and relative lymphocyte blood count before treatment, as observed in men, was found in women. Conclusions: The obtained results indicate a significant and sex-depended impact of previous COVID-19 on the course of NSCLC. In women, an increase of the malignant process severity and a decrease in treatment effectiveness were observed. In men, a sharp increase in the incidence of NSCLC in the early stages may indicate the possibility of COVID-19-induced tumor process in the lungs. The combination of a normal or moderately elevated relative blood lymphocyte count before treatment with subsequent unfavorable NSCLC dynamics may be due to changes in the functional state of lymphocytes and loss of diagnostic value of this indicator in men under the influence of COVID-19.
The ATLAS study: A first-in-human phase 1/2 trial of [Ac-225]RTX-2358 in patients with relapsed or refractory soft tissue sarcoma.
TPS11598 Background: Fibroblast Activation Protein (FAP) is expressed on the surface of cancer-associated fibroblasts and is involved in the formation, maintenance, and spread of tumors. Sarcoma frequently demonstrates high expression of FAP on the tumor cells themselves in contrast to other solid tumors, where it is mainly expressed on CAFs within the tumor stroma. Radioligand therapies utilizing alpha emitting isotopes such as Ac-225 have emerged as promising treatment strategies across multiple targets and indications in oncology. Ac-225 and its daughter radionuclides emit high-energy alpha particles capable of inducing double-stranded DNA breaks, leading to significant cytotoxic effects within cells. Early clinical data for other Ac-225-labeled compounds have shown promising outcomes, particularly in settings where traditional therapies have failed. [Ac-225] RTX-2358 (Ratio Therapeutics Inc, Boston, MA) is a novel FAP-targeted radioligand designed for specific high-affinity binding, resulting in prolonged tumor residence and limited normal tissue uptake. This sustained tumor retention leads to extended delivery of cytotoxic radiation to FAP-expressing tumors. A beta-emitting analog, [Lu-177]RTX-2358, has been administered to more than 25 patients under the German §13.2b compassionate use framework across multiple tumor types. Longitudinal SPECT imaging performed as late as 14 days after administration demonstrated persistent tumor retention with minimal washout. Based on time–activity curve analysis from these data, tumor biological half-time is estimated to be well in excess of 1,000 hours. Renal clearance was observed to be consistent with that reported for established lutetium-177–labeled radioligand therapies. Methods: This study is a seamless Phase 1 / 2 dose escalation study. The Phase 1 portion consists of a 3 x 3 dose escalation design, with patients treated in 3 planned dose escalation cohorts (7.5, 11.25 and 15 MBq) with up to 6, 8-week cycles of [Ac-225]RTX-2358. Backfill of phase 1 cohorts is permitted to facilitate selection of the recommended administered activity level for the subsequent Phase 2 expansion cohort. Dose escalation / de-escalation decisions will be made by a Safety Review Committee. Patients over 18yrs with a history of histologically confirmed relapsed or refractory soft tissue sarcoma (measurable disease per RECIST v1.1) are eligible if they have a positive [Cu-64]LNTH-1363S FAP PET, an ECOG PS 0 to 1, and adequate organ reserve and renal function. Recruitment of the first cohort was completed in December 2025. The ATLAS Study: NCT07156565 Clinical trial information: NCT07156565 .