Search Results (817)

Background/Objectives: Stroke remains a leading cause of disability in Japan, and early mobilization is an important strategy to prevent muscle atrophy and promote independence. However, the optimal intensity and duration of early rehabilitation remain unclear. This study aims to examine the association between rehabilitation dose during the acute phase of stroke and functional outcomes at 90 days post-onset. Methods: This multicenter prospective cohort study will enroll patients from twelve acute care hospitals across Japan, beginning in June 2026. Eligible patients are aged ≥ 18 years, expected to be hospitalized for ≥7 days, and initiated rehabilitation by day 2 after stroke onset. Rehabilitation dose will be quantified using the Mobilization Quantification Score (MQS). The primary outcome is functional status measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes include muscle atrophy assessed by ultrasound, the Barthel Index, and physical performance measures. Subgroup analyses will evaluate how stroke severity modifies the dose–response relationship. Results: As this is a study protocol, results are not yet available. The study is designed to clarify the relationship between early rehabilitation dose and functional recovery after stroke. Conclusions: This is the first large-scale Japanese study to assess early stroke rehabilitation dosage using a standardized tool. Findings are expected to provide evidence for individualized, evidence-based mobilization strategies to optimize functional outcomes in stroke patients. Full article

Objectives: This phase Ib study assessed the safety and compatibility of indirect oregovomab immunization and Toll-like-receptor-3 (TLR3) stimulation with immune adjuvant Hiltonol^® (poly-ICLC) and induced clinically relevant CA125-specific anti-tumor immunity in heavily pretreated patients with progressive platinum-resistant ovarian cancer (PROC). Methods: Patients with elevated serum CA125 level >50 U/mL received four intravenous infusions with 2 mg oregovomab followed by 2 mg Hiltonol^® intramuscular 30 min and 48 h post-oregovomab at weeks 0, 3, 6, and 9. At week 12, imaging was performed, and salvage chemotherapy was allowed post-progression per the investigator’s discretion. The Fifth/final oregovomab with Hiltonol^® infusion was given at week 16. Results: Fifteen enrolled patients were analyzed for safety and efficacy. Thirteen (87%) patients completed at least three Hiltonol^® infusions with oregovomab, specifically, two cycles (n = 2), three cycles (n = 2), four cycles (n = 3), and five cycles (n = 8). Adverse events included mild fatigue, flu-like symptoms, chills, axillary pain, and injection site discomfort in 13 (87%) patients. Serious adverse events were reported in seven (47%) patients, including Grade 3 hypertension (n = 2), thrombocytopenia (n = 1), and Grade 3 events attributed to underlying disease (n = 4). Ten (67%) patients had disease progression, three (20%) had stable disease, and two were unevaluable. Early humoral response by week 6 was observed in seven of nine (77%) patients, median progression-free survival was 2.7 months (95% confidence interval [CI]: 2.2, 3.3), and median overall survival was 15.0 months (95% CI: 8.2–23.9). Conclusions: The safety and compatibility of combining oregovomab with Hiltonol^® have been demonstrated in this study. The potential to enhance activity of chemotherapy using oregovomab indirect immunization and Hiltonol^® stimulation is proposed. Full article

Few studies provide insights on how to incorporate community members’ perspectives of genomic research during the early phases of study development. Engaging with community members early and consistently throughout the research lifecycle could help identify and mitigate barriers to genomic research participation, particularly among groups with rare and understudied cancers. Methods: The Washington University Participant Engagement and Cancer Genome Sequencing (WU-PE-CGS) study formed a Participant Engagement Advisory Board (PEAB) consisting of patients, patient advocates, and patient advocacy organizations who represented the three understudied cancer populations: cholangiocarcinoma, early-onset colorectal cancer in Black Americans, and multiple myeloma in Black Americans. PEAB members were involved in PE-CGS from the time of the grant submission and provided input on key study procedures by participating in monthly project meetings and serving on the leadership team. PEAB recommendations are described in this process paper. Results: The PEAB provided key feedback on recruitment, consent, and survey development. Recruitment optimization focused on making the script more concise, tailoring to participant’s locale, and providing clearer participation expectations. Consent improvements prioritized key information, addressed data protection, and clarified the process of returning genetic results. Survey enhancements included refining scientific terminology and ensuring inclusivity across the cancer continuum. Conclusions: The PEAB provided valuable feedback that improved the development and implementation of WU-PE-CGS research processes. Incorporating the PEAB’s suggestions helped ensure that patients with rare and understudied cancers were successfully enrolled into the WU-PE-CGS. The PEAB will continue to contribute throughout all study phases. Full article

Background: Following SARS-CoV-2 infection, the necessity of vaccination after natural infection remains uncertain. However, many asymptomatic individuals who test negative virologically may nevertheless receive vaccination without being aware of their prior infection. Investigating the implications for vaccine safety and efficacy is crucial. Methods: We analyzed the daily fluctuations in anti-SARS-CoV-2 IgG antibody levels during the enrollment period of a phase 3 randomized, double-blinded, placebo-controlled clinical trial of a tetravalent COVID-19 protein vaccine, SCTV01E. Additionally, we investigated the relationship between baseline IgG levels and their protection against COVID-19 in participants who received placebo. Results: The daily enrolled participants with different baseline IgG levels (<338 BAU/mL, 338–1000 BAU/mL, >1000 BAU/mL) showed dynamic changes with the enrollment date. Among participants with baseline IgG levels < 338 BAU/mL, vaccination conferred a relative protective efficacy of 69.15% (95% CI: 51.14–80.52%) against symptomatic SARS-CoV-2 infection compared with the control group. Conversely, in those with higher baseline IgG levels (≥338 BAU/mL), vaccination did not confer additional benefit. In the placebo group, the relative protection in participants with baseline IgG levels ≥ 338 BAU/mL was 93.79% (87.60%, 96.89%) compared to that of those with baseline IgG levels < 338 BAU/mL. The safety profile of SCTV01E in participants with baseline IgG ≥ 338 BAU/mL was comparable to that in participants with <338 BAU/mL, with favorable safety profiles. Conclusions: During the SCTV01E phase 3 clinical trial, an anti-SARS-CoV-2 IgG antibody IgG level of 338 BAU/mL was suitable for screening individuals in the early phase post-infection alongside virological tests. Vaccinating the infected population was safe and did not compromise efficacy. Clinical Trial: NCT05308576. Full article

Background: The outcomes of patients with peritoneal metastases from gastric cancer (GCPMs) remain dismal, with an overall survival (OS) of less than 1 year. Approaches reported from East Asia include normothermic intraperitoneal systemic chemotherapy, aimed at downstaging the disease, allowing an R0 resection. This is the first Western study evaluating a bidirectional regimen in a neoadjuvant setting of GCPMs. This phase II study evaluates the tolerability, efficacy and conversion surgery rate. Methods: Patients with PCI < 13 without ascites or HER2 overexpression and no extraperitoneal spread were enrolled starting in January 2018. After staging laparoscopy combined with PIPAC (cisplatin + doxorubicin), NIPS began following Yonemura’s schedule: cisplatin (30 mg/m²) + docetaxel (30 mg/m²), intraperitoneally (day 1); capecitabine 1000 mg/m², orally (days 2–15); and cisplatin (30 mg/m²) + docetaxel (30 mg/m²), intravenous (day 8). After three cycles, patients with no progressive disease and negative peritoneal cytology underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Three additional NIPS cycles were reserved for patients who underwent surgery. Results: Among the 25 treated patients with 17.3-month (95%CI: 10.4; NA) OS, no adverse events (CTCAE) ≥ G3 arose. With a 52% conversion surgery rate, 13 patients underwent CRS combined with HIPEC (cisplatin 100 mg/m²), 10 with CC0 status 3 with CC experienced no operative mortality, and major complications rated Clavien–Dindo IIIB occurred in 2 patients (15.4%). The median OS for patients undergoing surgery was 26 (95%CI: 23.1; NA) months, with progression-free survival of 20 (95%CI: 16.7–NA) months. Conclusions: NIPS is safe and effective. The conversion rate in our Western patients is comparable to that reported in Eastern Asian countries. Full article

Background/Objectives: Spontaneous intracranial hypotension (SIH), caused by spinal cerebrospinal fluid (CSF) leakage, commonly presents with orthostatic headache and CSF hypovolemia. While CSF dynamics in the cerebral aqueduct are well studied, alterations in spinal CSF flow remain less defined. We aimed to quantitatively assess spinal CSF flow at C2 using phase-contrast (PC) MRI enhanced by artificial intelligence (AI) and to evaluate its utility for diagnosing SIH and predicting responses to epidural blood patch (EBP). Methods: We enrolled 31 patients with MRI-confirmed SIH and 26 age- and sex-matched healthy volunteers (HVs). All participants underwent ECG-gated cine PC-MRI at the C2 level and whole-spine MR myelography. AI-based segmentation using YOLOv4 and a pulsatility-based algorithm was used to extract quantitative CSF flow metrics. Between-group comparisons were analyzed using Mann–Whitney U tests, and receiver operating characteristic (ROC) analysis was used to evaluate diagnostic and predictive performance. Results: Compared to HVs, SIH patients showed significantly reduced CSF flow parameters across all metrics, including upward/downward mean flow, peak flow, total flow per cycle, and absolute stroke volume (all p < 0.001). ROC analysis revealed excellent diagnostic accuracy for multiple parameters, particularly downward peak flow (AUC = 0.844) and summation of peak flow (AUC = 0.841). Importantly, baseline CSF flow metrics significantly distinguished patients who required one versus multiple epidural blood patches (EBPs) (all p < 0.001). ROC analysis demonstrated that several parameters achieved near-perfect to perfect accuracy in predicting EBP success, with AUCs up to 1.0 and 100% sensitivity/specificity. Conclusions: AI-enhanced PC-MRI enables the robust, quantitative evaluation of spinal CSF dynamics in SIH. These flow metrics not only differentiate SIH patients from healthy individuals but also predict response to EBP treatment with high accuracy. Quantitative CSF flow analysis may support both diagnosis and personalized treatment planning in SIH. Full article

Objectives: The varicella vaccine (VarV) produced by Sinovac (Dalian) obtained World Health Organization (WHO) prequalification in November 2022. However, no direct comparative studies have been conducted between VarV and other WHO-prequalified varicella vaccines. The study aimed to assess the immunogenicity and safety of Sinovac’s VarV compared with Merck Sharp & Dohme’s (MSD) VARIVAX^® (Moorgate, London, UK) following a single dose administration. Methods: This Phase III, randomized, double-blind, active-controlled, non-inferiority trial was conducted in the Philippines. Healthy children aged 12 to 15 months were enrolled. Eligible participants were randomly assigned (1:1) to receive a single dose of varicella vaccine either manufactured by Sinovac (Test group) or MSD (Active control group). Immunogenicity was evaluated 6 weeks after vaccination by enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity endpoint was seroresponse rate 6 weeks after vaccination. Seroresponse rate was defined as varicella-zoster virus (VZV) antibody concentration ≥ 10 mIU/mL in participants who were seronegative (antibody concentration < 10 mIU/mL) at baseline. The secondary endpoint was the corresponding geometric mean concentration (GMC). Adverse events (AEs) and serious adverse events (SAEs) were monitored for 6 weeks after vaccination. Results: Among the 484 participants analyzed, the seroresponse rates 6 weeks after vaccination were 98.85% and 98.88% in the Test group and Active control group, respectively, with a difference of −0.03% (95% CI: −3.10%, 2.99%), which exceeded the predefined non-inferiority margin of −10%. The corresponding GMCs were 35.73 mIU/mL and 37.34 mIU/mL, respectively, with the ratio of 0.96 (95% CI: 0.86, 1.06), also exceeding the predefined non-inferiority margin of 0.67. Furthermore, the incidence of adverse reactions (ARs) in the Test group was lower than that in the Active control group (38.08% vs. 55.51%). Conclusions: Sinovac’s VarV demonstrated non-inferior immunogenicity to WHO-prequalified comparator vaccine (VARIVAX^®) and favorable safety profile. These findings indicated that VarV (Sinovac, Beijing, China) met WHO standards for varicella vaccine evaluation, supporting its global use consideration. Full article

Background: The persistence of non-neonatal tetanus (non-NT) highlights the necessity of adult booster vaccines and post-traumatic prophylaxis. This Phase I/III clinical trial aimed to evaluate the safety and immunogenicity of a new adsorbed tetanus vaccine. Methods: A randomized, double-blind, positive-controlled clinical trial was conducted in Henan Province, China. A total of 1258 healthy participants aged 18–44 years (60 in Phase I and 1198 in Phase III) were enrolled, with no history of tetanus infection, or tetanus toxoid-containing vaccines (TTCVs) vaccination within the past 10 years. The participants were randomly assigned at a 1:1 ratio to receive a single dose of either the investigational vaccine or the licensed control vaccine. The Phase III clinical trial was initiated subsequent to the 7-day safety observation period following vaccination in the Phase I trial. The objective of the Phase III clinical trial was to assess the non-inferiority of the seroconversion rate of tetanus antibodies at 30 days post-vaccination with the investigational vaccine compared to the control vaccine. Serum samples were collected prior to and at 30 days post-vaccination. Adverse events were monitored for 30 days, with serious adverse events (SAEs) followed up for 6 months post-vaccination. Results: The investigational group achieved a seroconversion rate of 99.48%, which was non-inferior to that of the control group (99.66%), with a negligible rate difference of −0.17% (95% confidence interval [CI]: −1.20%, 0.78%). The investigational group exhibited a significantly higher geometric mean concentration (GMC) of antibodies (4.721 IU/mL vs. 3.627 IU/mL, p < 0.0001). Among the susceptible participants, the seroconversion rates were 99.78% in the investigational group and 99.79% in the control group, respectively, with a non-inferior rate difference of −0.01% (95%CI: −1.06%, 0.97%). Furthermore, the investigational group showed a low incidence of adverse reactions (ARs) within 30 days post-vaccination (12.26%), which was comparable to that of the control group (13.65%). All the reported ARs were mild or moderate, and no SAEs were associated with the vaccination. Conclusions: The new adsorbed tetanus vaccine demonstrated favorable safety and comparable immunogenicity to the marketed control vaccine, with a significantly higher antibody GMC, supporting its clinical application in tetanus prevention. Full article

Background: Elevated BMI in women is linked to metabolic and endocrine imbalances that impair fertility and increase pregnancy risks. While >10% weight loss before an Assisted reproductive technology (ART) treatment may improve outcomes, sustained results through conventional diets are challenging. A very-low calorie ketogenic diet (VLCKD) promotes rapid fat loss while preserving lean mass and may offer long-term benefits. This study evaluated the efficacy (≥10% weight loss without lean mass reduction), adherence, metabolic effects, and pregnancy outcomes of a meal replacement VLCKD in women with overweight or obesity scheduled for ART. Methods: This monocentric, prospective case-series was conducted at the Obesity and Work Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan (September 2019–September 2023). Eligible women underwent a three-phase dietary program: a 3-month VLCKD (<800 kcal/day), a 6-month transition with gradual carbohydrate reintroduction, and a Mediterranean-style maintenance diet. Participants were monitored for safety, body composition, adherence, and biochemical changes. Results: Of 52 women enrolled, 40 initiated the VLCKD; 27 (68%) achieved ≥10% weight loss while preserving lean mass. Eleven conceived naturally during or after the diet; 22 underwent ART, with 12 additional pregnancies. This corresponds to a 58% pregnancy rate among those who began the VLCKD. Significant improvements were observed in body mass index (BMI), fat mass, waist circumference, glucose metabolism, lipid profile, and liver function. No adverse events were reported. Conclusions: A meal replacement VLCKD protocol is feasible, well-tolerated, and associated with significant improvements in weight, especially in body composition, metabolic health, and potentially outcomes in women with overweight or obesity awaiting ART. Full article

Background/objectives: MDG1011 is a Preferentially Expressed Antigen in Melanoma (PRAME)-specific autologous T cell receptor (TCR) T cell therapy for HLA-A*02:01-positive patients. Data from the first-in-human (FIH) clinical trial, CD-TCR-001, are reported here regarding treatment feasibility, safety, tolerability, and clinical activity of MDG1011 in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). Methods: Nine of thirteen enrolled patients received MDG1011 at dose levels ranging from 0.1 to 5 × 10⁶ TCR-T cells per kg body weight. In addition to clinical assessments, immune monitoring of cytokines associated with cytokine release syndrome (CRS), presence and persistence of MDG1011, and changes in levels of PRAME mRNA were used to assess safety and potential biological activity at defined time points. Results: The treatment was well tolerated. No dose-limiting toxicities (DLTs) were observed, and the most common serious adverse events were associated with lymphodepleting chemotherapy and/or disease progression. Various parameters, such as measurable clinical responses in two patients, the occurrence of CRS in two additional patients, and reductions in PRAME mRNA levels in bone marrow (BM) or peripheral blood (PB) in seven patients, served as signs of the clinical and biological activity of MDG1011 TCR-T therapy. Conclusions: Patients enrolled in the phase 1 part of CD-TCR-001 displayed signs of potential clinical and biological activity of MDG1011 among the small number of patients studied. Advanced disease stage and rapid progression in the r/r AML patients limited clinical impact. The acceptable safety profile of MDG1011 merits further investigation of this TCR-T therapy, potentially in patients at an earlier stage of their disease and with lower tumor burden. Full article

Background: Hormone-receptor-positive (HR+)/HER2-negative (HER2−) breast cancer (BC) is characterized by low immunogenicity and an immunosuppressive microenvironment. These features likely contribute to the inconsistent clinical activity of immune checkpoint inhibitors (ICIs) in this BC subtype. We conducted a systematic review of clinical trials evaluating ICIs in HR+/HER2− BC patients, focusing on potential biomarkers of response and resistance to these drugs. Methods: We systematically searched in Medline via PubMed, EMBASE, and CENTRAL for phase II/III clinical trials published between 2013 and 2023, testing ICIs alone or in combination with other agents in HR+/HER2− BC patients at any stage. All the searches were performed up to 27 January 2024. Data on study characteristics, clinical outcomes, and biomarker profiles were extracted, and due to study heterogeneity, a narrative synthesis was performed, without risk-of-bias assessment or meta-analysis. Results: Twenty-five studies were included, with 3298 patients enrolled overall. Eighteen of these trials enrolled patients with advanced disease. All trials investigated ICI combination regimens, more frequently with chemotherapy, CDK4/6 inhibitors, or other immunotherapeutic agents. Most of the studies enrolling patients with advanced disease failed to show a significant clinical activity of ICIs. In the early setting, neoadjuvant chemo-immunotherapy with nivolumab or pembrolizumab increased the rate of complete responses compared to chemotherapy alone. Moreover, high programmed death-ligand 1 (PD-L1) expression, low ER (estrogen receptor), and high tumor-infiltrating lymphocyte (TIL) levels correlated with improved outcomes. Consistently, markers indicating enhanced immune activation, such as the MammaPrint High 2 (MP2) genomic signature, were associated with increased ICI sensitivity. Discussion: Despite the limited overall efficacy, ICIs may represent a viable therapeutic option for a selected subset of HR+/HER2− BC patients. However, this systematic review is limited by study heterogeneity and the inclusion of ongoing or immature trials, which prevents quantitative analysis and may affect future conclusions on ICIs in HR+/HER2− breast cancer. Finally, optimized combination strategies could enhance tumor immunogenicity, while predictive biomarkers such as PD-L1, TILs, or specific genomic signatures could identify responsive patients. Full article

Fibromyalgia (FM) is a complex chronic syndrome characterized by widespread pain, fatigue, and gastrointestinal complaints. Clinical observations and preliminary metabolomic data suggest a possible link between symptom severity and intestinal dysbiosis, including fungal overgrowth. This study investigates whether a carb-free oloproteic diet can beneficially modulate the gut microbiota in FM patients. Thirty-four female patients with diagnosed FM were enrolled in a controlled, parallel-arm nutritional intervention. Group FM1 (n = 22) followed a 45-day carb-free oloproteic diet followed by a 45-day low-glycemic (LOGI) diet. Group FM2 (n = 12) received a continuous LOGI diet for 90 days. They were collected at baseline (T0), after 45 days (T45), and at 90 days (T90). Microbial profiles were analyzed by 16S and 18S rRNA gene sequencing to assess bacterial and fungal composition. In FM1, the oloproteic phase led to a marked reduction in fungal abundance (Ascomycota) and an increase in butyrate-producing bacteria such as Faecalibacterium and Roseburia. These changes were partially reversed after the LOGI phase. In FM2, no significant microbiota shifts were observed. Clinical improvements paralleled microbiota modulation only in FM1. The carb-free oloproteic diet may support gut microbial rebalancing in FM, particularly through transient suppression of fungal overgrowth. These findings support further investigation into nutritional strategies targeting dysbiosis in FM management. Full article

The reliability of molecular diagnostic and prognostic tools is contingent on the quality of biospecimens, which are often collected during surgical procedures. This study investigated the impact of surgical manipulation on gene expression in the urinary bladder mucosa during radical cystectomy. Seventeen patients with urinary bladder cancer were enrolled, and paired pre- and post-surgery biopsies were analyzed. Pre-surgical biopsies were obtained in situ under anesthesia, while post-surgical biopsies were collected ex vivo following bladder removal. Total RNA was extracted, and gene expression was assessed using qPCR arrays, measuring the expression of 374 inflammation-related genes. The findings from the exploratory phase were further validated by analyzing key genes in an independent patient cohort using TaqMan^® gene-specific assays. Exploratory analysis revealed significant differential expression in 27 genes, with key genes such as IL6, FOS, and PTGS2 being upregulated post-surgery. Validation of five selected genes in an independent cohort confirmed these findings. This study reinforces the necessity of accounting for surgery-induced alterations in gene expression when analyzing tissue samples collected intraoperatively. By elucidating the molecular impact of surgical interventions, this work provides critical insights for refining experimental methodologies and enhancing the interpretability of gene expression studies in clinical and research settings. Full article

Background: The etiopathogenesis of IBD is not fully known; however, both genetic and environmental risk factors, including diet, are contributors to the disease. The present study aimed to determine the effect of dietary inflammatory potential, assessed using the Dietary Inflammatory Index (DII), on disease activity and inflammatory markers, such as IL-6, IL-1β, and IL-10, in patients with IBD. Methods: The study enrolled 90 patients with IBD. Dietary intake was assessed based on a 24 h questionnaire interview conducted in each subject three times. Based on these data, the DII for each subject was calculated. The serum levels of IL-6, IL-1 β, and IL-10 were determined with the quantitative sandwich enzyme-linked immunosorbent assay (ELISA). Results: The mean DII value was −0.39 ± 0.52 and did not differ significantly between the groups with CD and UC (−0.42 ± 0.47 vs. −0.37 ± 0.54, p = 0.6452, respectively); however, it was remarkably lower among patients in remission and with mild disease compared to those in the active phase of the disease (−0.45 ± 0.61 vs. −0.23 ± 0.65, p = 0.0217). Considering the DII tertiles, the subjects differed significantly in terms of age and disease activity. Logistic regression analysis of disease severity and DII in the crude model revealed that the probability of severe disease in IBD patients increased with higher DII scores. Conclusions: The results of the present study revealed a significant association between pro-inflammatory diet and IBD severity, which indicates a need to formulate an anti-inflammatory diet to reduce disease severity in patients with CD and UC. Full article

Study Aim: Patients with high-risk Ewing sarcoma (ES) have dismal outcomes despite aggressive multimodal therapy. This phase II, single-institution study evaluated the response rate to two up-front cycles of irinotecan, temozolomide, and temsirolimus (ITT) and assessed the tolerability of maintenance therapy following standard treatment in high-risk ES. Methods: Eligible patients had newly diagnosed high-risk ES (age ≥14 years old, metastatic disease, or primary pelvic tumor). The therapy included two cycles of window therapy (ITT) followed by interval-compressed chemotherapy (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide) and maintenance therapy (cyclophosphamide, sorafenib, and bevacizumab). A two-stage sequential design was employed to assess a >50% WHO response (CR or PR) with 80% power. Patients who required emergent radiation were excluded from receiving window therapy. Results: Sixteen patients (median age 12.2 years; range 4.8–23.6 years) were enrolled (12 evaluable for overall response, 10 for primary tumor response). Only three achieved a PR to window therapy, leading to study closure. All evaluable patients demonstrated a decline in their primary tumor volume (mean decline: 32.5%, standard deviation: 17.6%, p-value: 0.0005) and SUV peak (mean decline: 49.9%, standard deviation: 21.1%, p-value: 0.002). Maintenance therapy was well tolerated, with only 2/13 patients discontinuing due to toxicity. Conclusions: ITT did not achieve the prespecified response rate of 50%, according to WHO criteria; however, all patients exhibited decreased volume and metabolic activity, highlighting the limitations of conventional response assessments. Maintenance therapy was feasible and well tolerated. Although limited by small sample size, heterogeneous disease presentations, and the absence of a control arm, this study supports further evaluation of ITT and a maintenance approach in larger, randomized trials for high-risk ES. Full article