tbuckley/cabot-search huggingface dataset:
<i>NOTCH1</i> Mutation and Survival Analysis of Tislelizumab in Advanced or Metastatic Esophageal Squamous Cell Carcinoma: A Biomarker Analysis From the Randomized, Phase III, RATIONALE-302 Trial
Authors: Zhihao Lu, Wenting Du, Xi Jiao, Yanni Wang, Jingwen Shi, Yang Shi, Yongqian Shu, Zuoxing Niu, Hiroki Hara, Jun Wu, Chih-Hung Hsu, Eric Van Cutsem, Malcolm V. Brock, Zhang Zhang, Ningning Ding, Yun Zhang, Zhirong Shen, Lin Shen
Journal: Journal of Clinical Oncology (2025)

PURPOSE Although multiple agents targeting PD-1 have been approved as second-line treatment for esophageal squamous cell carcinoma (ESCC), only a fraction of patients derive long-term survival. Hence, reliable predictive biomarkers are urgently needed. METHODS Comprehensive tumor genomic profiling and transcriptome sequencing were performed on samples from the RATIONALE-302 study. We also conducted single-cell RNA sequencing analysis on Notch1 knockdown ESCC murine models to further explore the potential molecular mechanisms underlying anti–PD-1 benefit. RESULTS We identified NOTCH1 mutation as a potential predictive biomarker for longer overall survival (OS) with tislelizumab versus chemotherapy (18.4 months v 5.3 months; hazard ratio, 0.35 [95% CI, 0.17 to 0.71]). At the transcriptional level, type I IFN (IFN-I)/toll-like receptor expression signatures were positively associated with OS benefit of tislelizumab, whereas B-cell and neutrophil signatures predicted unfavorable OS. Exploratory analyses showed that the presence of NOTCH1 mutation correlated with enrichment of IFN-I signatures and reduced infiltration of B cells and neutrophils. In murine models, comparative single-cell transcriptome analyses further revealed that Notch1 deficiency facilitated a more immunologically activated tumor microenvironment which potentiated anti–PD-1 treatment. CONCLUSION Our data provide novel insights for anti–PD-1 treatment selection using NOTCH1 mutations and may provide a rationale for combination therapy in ESCC.
Rare Immuno-Induced Keratoacanthomas Showed on 18F-FDG PET/CT in a Metastatic Melanoma Patient
Authors: Naia Oillarburu, Cécile Pages, Vincent Sibaud, Laurence Lamant, Marie Terroir
Journal: Clinical Nuclear Medicine (2025)

Abstract A 76-year-old man managed for stage IV advanced melanoma was treated with nivolumab-ipilimumab, complicated by corticotropic insufficiency, hypothyroidism, and rash. At first evaluation, 18 F-FDG PET/CT clearly showed complete metabolic response allowing continued treatment with nivolumab alone. At 6 months, 18 F-FDG PET/CT fully confirmed the persistence of complete metabolic response but showed the appearance of cutaneous focal uptakes of both lateral thighs and a cutaneous diffuse uptake on lower limbs. Clinically, he had a severe verrucous lichenoid eruption with eruptive keratoacanthomas, confirmed after resection. We report a case of rare immunotherapy-induced keratoacanthomas first showed by 18 F-FDG PET/CT.
Medium-Vessel Vasculitis on FDG-PET/CT at Initial Presentation and Relapse
Authors: Pierre-Adrien Vion, Cindy Marques, Sarah Boughdad
Journal: Clinical Nuclear Medicine (2025)

A 76-year-old man presented with morning facial edema, forearm induration, testicular pain, and a major inflammatory syndrome. Contrast-enhanced CT was inconclusive. Conversely, FDG-PET/CT showed pathological uptake of medium-vessels, particularly in the right arm and facial soft tissues, leading to the diagnosis of medium-vessel vasculitis. Symptoms vanished after methotrexate and corticosteroid initiation. While undergoing progressive corticosteroid dose reduction, he presented with lower limb myalgia. A second FDG-PET/CT confirmed the relapse, with extensive uptake of the intermuscular perforating arteries of the limb. This clinical report illustrates the good correlation between clinical symptoms and FDG-PET/CT findings, in these challenging to diagnose vasculitides.
[18F]FDG PET-CT in Weber-Christian Disease
Authors: Vicky Betech-Antar, Miguel Barrio-Piqueras, Juan J. Rosales, Inmaculada Colina, Macarena Rodriguez-Fraile
Journal: Clinical Nuclear Medicine (2025)

A 46-year-old woman with relapsing fever and painful pelvic subcutaneous nodules was referred to our center for a second opinion. Despite antibiotic and corticoid treatment, inflammation markers remained high. FDG-PET/CT was performed to evaluate the possible cause of her clinical condition, exclude systemic disease and evaluate the extension and inflammation of the nodules. FDG-PET/CT showed multiple abdominopelvic subcutaneous soft tissue foci without visceral involvement. The review of a previous nodule biopsy revealed Weber-Christian Disease (WCD), a rare disorder characterized by idiopathic nodular panniculitis, fever, and systemic inflammation. WCD is a diagnosis of exclusion when no other cause of panniculitis can be identified
Significant 99mTc-FAPI-46 Uptake in 2 Cases of TENIS Syndrome With Negative Tc-OCTREOTIDE Scan, a New Hope in Theranostic Applications
Authors: Mitra Ghahraman, Kamran Aryana, Seyed Rasoul Zakavi, Farivash Karamian, Atena Aghaee
Journal: Clinical Nuclear Medicine (2025)

The role of fibroblast activation protein inhibitor (FAPI) as a novel radiopharmaceutical in the field of cancer diagnosis and treatment (theranostic) is still under investigation. We present 2 patients of differentiated thyroid cancer with thyroglobulin elevation and negative iodine scintigraphy (TENIS syndrome) who underwent 99 mTc-OCTREOTIDE scan and 99mTc-FAPI SPECT/CT to evaluate possible sites for metastasis. 99 mTc-OCTREOTIDE scan showed no remarkable uptake in these patients. On the other hand, foci of metastatic disease were found, with intense 99 mTc-FAPI-46 uptake. Malignant FAPI uptake was evident in the lungs, liver, adrenal, and abdominal lymph nodes in a patient and in the lungs of another one. Due to proper uptake in diagnostic scans, these patients were recognized as a suitable candidate for treatment with 177 Lu-FAPI-46.
Below-the-Radar: A Case of Extensive Osseous Metastasis of Prostate Cancer Confined Exclusively to One Lower Limb
Authors: Jan Heilinger, Dominic Ufton, Uta Drebber, Matthias Schmidt, Alexander Drzezga
Journal: Clinical Nuclear Medicine (2025)

Osseous metastases are a common finding in prostate cancer, usually affecting the central skeleton. Metastases in the peripheral skeleton are less frequent but can occur as isolated findings as well. Therefore, imaging protocols limited to the trunk may miss such lesions and extended range (total-body) PSMA-PET/CT may be helpful for comprehensive evaluation, especially when peripheral metastases are suspected, for example, due to clinical symptoms.
Ectopic Right Kidney Imaged With Dynamic 82Rb PET/CT
Authors: Nasir Gözlügöl, Hasan Sari, Ali Afshar-Oromieh, Axel Rominger, Federico Caobelli
Journal: Clinical Nuclear Medicine (2025)

Ectopic kidney in the thoracic region are infrequent in clinical practice. A 64-year-old man underwent a Rubidium ( 82 Rb) positron emission tomography/computed tomography (PET-CT) scan for the evaluation of myocardial ischemia due to a diagnosed 2-vessel coronary artery disease. While no myocardial perfusion abnormalities were detected, the scan showed the presence of a diaphragmatic high stand on the right side, with evidence of an ectopic kidney. We here present static and flow dynamic images of this rare finding 1–3 .
Unsuspected Spondylolysis on FDG PET/CT in a Pediatric Patient With Osteosarcoma
Authors: Pensiree Attaseth, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2025)

Lumbar spondylolysis can be asymptomatic but is a common cause of low back pain in adolescent athletes. We report a rare case of focal increased FDG uptake at the left pars interarticularis of L5 vertebra, along with an associated transverse fracture line on 18 F-FDG PET/CT, in a 15-year-old boy with newly diagnosed osteosarcoma. This led to the incidental diagnosis of L5 spondylolysis. Attention to CT findings and history-taking is prerequisite to avoid misinterpretation of the FDG PET/CT in this clinical setting.
Collagen Vascular Disease–Associated Interstitial Pneumonia With Accumulation of 18F-fluoroestradiol
Authors: Sumika Yasumura, Kanae K. Miyake, Yoichi Shimizu, Tomomi Nobashi, Yuji Nakamoto
Journal: Clinical Nuclear Medicine (2025)

18 F-fluoroestradiol ( 18 F-FES) is a PET radiotracer that binds to the estrogen receptor (ER) in the nucleus of ER-expressing cells and is increasingly used clinically in breast cancer patients to visualize ER expression in lesions. Although 18 F-FES accumulation is generally specific, radiation-induced pneumonitis can produce false-positive results, but the underlying mechanisms remain largely unclear. Here, we report the case of a 72-year-old woman with known collagen vascular disease–associated interstitial pneumonia and the accumulation of 18 F-FES on 18 F-FES-PET/CT, which was conducted to investigate suspected recurrent breast cancer.
Rosai-Dorfman Disease Mimicking Metastasis to the Spleen From Breast Cancer
Authors: Zamaan Hooda, Yang Lu, Reza John Mehran, Cesar Moran, Carlos Hernando Barcenas
Journal: Clinical Nuclear Medicine (2025)

Rosai-Dorfman disease is a non-Langerhans cell histiocytosis with ubiquitous distribution. Although more common in lymph nodes, it has been described in many organ systems. The current case depicts a 54-year-old woman with a history of estrogen receptor-positive breast carcinoma who showed different image features of metastatic lymph nodes and splenic Rosai-Dorfman disease on FDG and FES PET/CT scans.
Taletrectinib in <i>ROS1</i> + Non–Small Cell Lung Cancer: TRUST
Authors: Maurice Pérol, Wei Li, Nathan A. Pennell, Geoffrey Liu, Yuichiro Ohe, Filippo De Braud, Misako Nagasaka, Enriqueta Felip, Anwen Xiong, Yongchang Zhang, Huijie Fan, Xicheng Wang, Shuanglian Li, Rose K. Lai, Feiwu Ran, Xianyu Zhang, Wenfeng Chen, Lyudmila Bazhenova, Caicun Zhou
Journal: Journal of Clinical Oncology (2025)

PURPOSE Taletrectinib is an oral, potent, CNS-active, selective, next-generation ROS1 tyrosine kinase inhibitor (TKI). We report integrated efficacy and safety from registrational taletrectinib studies in ROS1 + non–small cell lung cancer. METHODS TRUST-I and TRUST-II were phase II, single-arm, open-label, nonrandomized, multicenter trials. Efficacy outcomes were pooled from TRUST-I and TRUST-II pivotal cohorts. The safety population comprised all patients treated with once-daily oral taletrectinib 600 mg pooled across the taletrectinib clinical program. The primary end point was independent review committee–assessed confirmed objective response rate (cORR). Secondary outcomes included intracranial (IC)-ORR, progression-free survival (PFS), duration of response (DOR), and safety. RESULTS As of June 7, 2024, the efficacy-evaluable population included 273 patients in TRUST-I and TRUST-II. Among TKI-naïve patients (n = 160), the cORR was 88.8% and the IC-cORR was 76.5%; in TKI-pretreated patients (n = 113), the cORR was 55.8% and the IC-cORR was 65.6%. In TKI-naïve patients, the median DOR and median PFS were 44.2 and 45.6 months, respectively. In TKI-pretreated patients, the median DOR and median PFS were 16.6 and 9.7 months. The cORR in patients with G2032R mutation was 61.5% (8 of 13). Among 352 patients treated with taletrectinib 600 mg once daily, the most frequent treatment-emergent adverse events (TEAEs) were GI events (88%) and elevated AST (72%) and ALT (68%); most were grade 1. Neurologic TEAEs were infrequent (dizziness, 21%; dysgeusia, 15%) and mostly grade 1. TEAEs leading to discontinuations (6.5%) were low. CONCLUSION Taletrectinib showed a high response rate with durable responses, robust IC activity, prolonged PFS, favorable safety, and low rates of neurologic adverse events in TKI-naïve and pretreated patients.
Interpreting regulatory mechanisms of Hippo signaling through a deep learning sequence model
Authors: Khyati Dalal, Charles McAnany, Melanie Weilert, Mary Cathleen McKinney, Sabrina Krueger, Julia Zeitlinger
Journal: Cell Genomics (2025)

Signaling pathway components are well studied, but how they mediate cell-type-specific transcription responses is an unresolved problem. Using the Hippo pathway in mouse trophoblast stem cells as a model, we show that the DNA binding of signaling effectors is driven by cell-type-specific sequence rules that can be learned genome wide by deep learning models. Through model interpretation and experimental validation, we show that motifs for the cell-type-specific transcription factor TFAP2C enhance TEAD4/YAP1 binding in a nucleosome-range and distance-dependent manner, driving synergistic enhancer activation. We also discovered that Tead double motifs are widespread, highly active canonical response elements. Molecular dynamics simulations suggest that TEAD4 binds them cooperatively through surprisingly labile protein-protein interactions that depend on the DNA template. These results show that the response to signaling pathways is encoded in the cis-regulatory sequences and that interpreting the rules reveals insights into the mechanisms by which signaling effectors influence cell-type-specific enhancer activity.
Identification of a seasonal influenza vaccine–induced broadly protective neuraminidase antibody
Authors: Anders Madsen, Nisreen M.A. Okba, Tossapol Pholcharee, Hanover C. Matz, Huibin Lv, Maria Ibanez Trullen, Julian Q. Zhou, Jackson S. Turner, Aaron J. Schmitz, Fangjie Han, Stephen C. Horvath, Sameer Kumar Malladi, Florian Krammer, Nicholas C. Wu, Ali H. Ellebedy
Journal: The Journal of Experimental Medicine (2025)

Seasonal influenza viruses cause significant global illness and death annually, and the potential spillover of avian H5N1 poses a serious pandemic threat. Traditional influenza vaccines target the variable hemagglutinin (HA) protein, necessitating annual vaccine updates, while the slower-evolving neuraminidase (NA) presents a promising target for broader protection. We investigated the breadth of anti-NA B cell responses to seasonal influenza vaccination in humans. We screened plasmablast-derived monoclonal antibodies (mAbs) from three donors, identifying 11 clonally distinct NA mAbs from 268 vaccine-specific mAbs. Among these, mAb-297 showed exceptionally broad NA inhibition, effectively protecting mice against lethal doses of influenza A and B viruses, including H5N1. We show that mAb-297 targets a common binding motif in the conserved NA active site. Our findings show that while B cell responses against NA following conventional, egg-derived influenza vaccines are rare, inducing broadly protective NA antibodies through such vaccination remains feasible, highlighting the importance of improving NA immunogens to develop a more broadly protective influenza vaccine.
Safety and implementation of phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns
Authors: Avy Violari, Kennedy Otwombe, William Hahn, Shiyu Chen, Deirdre Josipovic, Vuyelwa Baba, Asimenia Angelidou, Kinga K Smolen, Ofer Levy, Nonhlanhla N Mkhize, Amanda S Woodward Davis, Troy M Martin, Barton F Haynes, Wilton B Williams, Zachary K Sagawa, James G Kublin, Laura Polakowski, Margaret Brewinski Isaacs, Catherine Yen, Georgia Tomaras, Lawrence Corey, Holly Janes, Glenda E Gray
Journal: Journal of Clinical Investigation (2025)

The neonatal immune system is uniquely poised to generate broadly neutralizing antibodies (bnAbs) and thus infants are ideal for evaluating HIV vaccine candidates. We present the design and safety of a new-in-infants glucopyranosyl lipid A (GLA)-stable emulsion (SE) adjuvant admixed with a first-in-infant CH505 transmitter-founder (CH505TF) gp120 immunogen designed to induce precursors for bnAbs against HIV. HVTN 135 is a phase I randomized, placebo-controlled trial of CH505TF+GLA-SE or placebo. Healthy infants aged ≤ 5 days, born to mothers living with HIV but HIV nucleic acid negative at birth were randomized to five doses of CH505TF + GLA-SE or placebo at birth and 8, 16, 32, and 54 weeks. 38 infants (median age = 4 days; interquartile range 4, 4.75 days) were enrolled November 2020 to January 2022. Among 28 (10) infants assigned to receive CH505TF + GLA-SE (placebo), most (32/38) completed the 5-dose immunization series and follow-up (35/38). Solicited local and systemic reactions were more frequent in vaccine (8, 28.6% local; 16, 57.1% systemic) vs. placebo recipients (1, 10% local, P = 0.25; 4, 40.0% systemic, P = 0.38). All events were Grade 1 except two Grade 2 events (pain, lethargy). Serious vaccine-related adverse events were not recorded. This study illustrates the feasibility of conducting trials of new-in-infants adjuvanted HIV vaccines in HIV-exposed infants receiving standard infant vaccinations. The safety profile of the CH505TF + GLA-SE vaccine was reassuring. gov NCT04607408. The trial was funded through National Institute of Allergy and Infectious Disease of the National Institutes of Health under grants UM1 AI068614 (HVTN Leadership and Operations Center), UM1 AI068635 (HVTN Statistical and Data Management Center), and UM1 AI068618 (HVTN Laboratory Center).
Comparative Evaluation of 68Ga-FAPI-04 PET for Initial N and M Staging in Gastric Cancer: A Study Against Histopathology and Contrast-Enhanced CT
Authors: Yiru Fu, Chunxia Qin, Mengting Li, Xiao Zhang, Yongkang Gai, Weiwei Ruan, Xiaoli Lan
Journal: Clinical Nuclear Medicine (2025)

Purpose: To evaluate the efficiency of 68 Ga-FAPI-04 PET (PET/MRI or PET/CT) for N and M staging in gastric carcinoma and compare outcomes with histopathology and contrast-enhanced computed tomography (CECT). Patients and Methods: Patients with gastric carcinoma who had undergone 68 Ga-FAPI-04 PET/MRI or PET/CT before treatment were retrospectively enrolled. Histopathology post lymphadenectomy was the gold standard for N staging, while histopathology and follow-up data were the reference for overall outcomes. The diagnostic efficiency of 68 Ga-FAPI-04 PET for detecting regional lymph node involvement and distant metastases was compared to that of CECT. Results: Sixty-two patients were enrolled. In 18 patients who underwent 68 Ga-FAPI-04 PET/MRI and lymphadenectomy, 532 lymph nodes were dissected. 68 Ga-FAPI-04 PET/MRI showed similar sensitivity, specificity, and accuracy compared to CECT (28.3% vs. 23.2%, 99.8% vs. 99.3%, and 86.5% vs. 85.2%, all P &gt; 0.05). Fifty-five patients had regional lymph node metastasis, 68 Ga-FAPI-04 PET exhibited comparable diagnostic efficiency to CECT, with sensitivity of 83.6% versus 87.3%, specificity of 100% versus 85.7%, accuracy of 85.5% versus 87.1% (all P &gt; 0.05). Excluding 3 patients with only abdominal CECT, 32 out of 59 patients had distant metastasis, with no significant differences in sensitivity, specificity, and accuracy between 68 Ga-FAPI-04 PET and CECT based on patient (100% vs. 87.5%, 92.6% vs. 96.3%, and 96.6% vs. 91.5%, all P &gt;0.05). Notably, 68 Ga-FAPI-04 PET outperformed CECT in detecting peritoneal, distant lymph nodes, bone, liver, and ovarian metastases by visualizing more lesions or greater lesion extent. Conclusions: 68 Ga-FAPI-04 PET exhibits comparable diagnostic performance to CECT for patient-based N staging and M staging of gastric cancer. However, it surpasses CECT in visualizing distant metastases.
Using mpMRI, PSMA, and GRPR PET to Assess Focal Therapy Eligibility and Plan Treatment in Biopsy-proven Low-/Intermediate-risk Prostate Cancer: A Whole-mount Pathology-based Study
Authors: Yujia Li, Jinhui Yang, Ling Xiao, Ming Zhou, Xiaomei Gao, Axel Rominger, Kuangyu Shi, Robert Seifert, Yi Cai, Yongxiang Tang, Shuo Hu
Journal: Clinical Nuclear Medicine (2025)

Purpose: Focal therapy (FT) is an emerging strategy for selectively ablating prostate cancer (PCa). However, existing challenges comprise conventional techniques inadequately identifying appropriate candidates and insufficient characterization of multifocality and sampling-biases in the biopsy-based trials. We evaluated the value of adding prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPR) PET to multiparametric MRI (PET/mpMRI) in preoperative assessments for FT, with whole-mount pathology as a comprehensive reference. Methods: A total of 38 men with biopsy-proven low-risk/intermediate-risk PCa underwent mpMRI, 68 Ga-PSMA, and 68 Ga-RM26 PET. Any focal lesion uptake (PET FL ) was considered for positive PET results, while PI-RADS for mpMRI interpretation. Index lesion was defined with the highest Gleason score or largest diameter. Detection rates for clinically significant (cs) PCa (lesion-level) and diagnostic performances for localization (segment-level) were assessed. Correct identification of FT-ineligible men (index lesion Grade Group&gt;3 or contralateral csPCa) was documented. Results: For detecting the overall 73 csPCa, both 68 Ga-PSMA and 68 Ga-RM26 PET/mpMRI demonstrated significantly higher detection rates (87.7% and 94.5% vs. 72.6%, P &lt;0.005), as well as higher accuracies for localization (0.87 and 0.90 vs. 0.81, P &lt;0.001) than mpMRI alone. Twenty of 38 (53%) men were confirmed FT-ineligible, of which mpMRI, 68 Ga-PSMA, and 68 Ga-RM26 PET/mpMRI identified 12 (60%), 20 (100%) and 17 (85%), respectively. Finally, 68 Ga-PSMA and 68 Ga-RM26 PET/mpMRI identified csPCa lesions in 88.5% and 100% of FT-eligible men, respectively. Conclusions: Combining PSMA/GRPR PET and mpMRI facilitates enhanced detection rates as well as higher accuracies for localization in localized PCa. 68 Ga-PSMA and 68 Ga-RM26 PET/mpMRI may serve as promising imaging tools to improve the preoperative assessments in FT candidates with low-risk/intermediate-risk PCa.
Epithelioid Rhabdomyosarcoma Demonstrated on 99mTc-MDP Bone Scintigraphy and 18F-FDG PET/CT
Authors: Ziqian Dong, Pengcheng Ren, Wenjun Bao, Lingge Wei, Peng Xie
Journal: Clinical Nuclear Medicine (2025)

A 60-year-old woman presented with the gradual aggravation of left hip pain. 99m Tc-MDP bone scintigraphy and 18 F-FDG PET/CT demonstrated intense radiotracer accumulation at the osteolytic lesion in the left acetabulum and pubis. The pathology confirmed the diagnosis of epithelioid rhabdomyosarcoma, a variant of rhabdomyosarcoma which is characterized by epithelioid morphology.
Squamous Cell Carcinoma of the Tonsil Unmasked by 68Ga-FAPI-46 PET/CT
Authors: Jiaqing Liu, Xiyi Liao, Yizhen Pang, Qin Lin, Haojun Chen
Journal: Clinical Nuclear Medicine (2025)

We reported 18 F-FDG and 68 Ga-FAPI-46 PET/CT findings in a 55-year-old woman with metastatic squamous cell carcinoma of the left neck. 18 F-FDG PET/CT was negative for the detection of primary malignancy. On 68 Ga-FAPI PET/CT, increased radiotracer uptake was noted in the left palatine tonsil, whereas low background uptake was observed in the right palatine tonsil. Based on the PET/CT findings, the patient underwent clinical examination and biopsy of the left tonsil. Histology demonstrated the presence of a squamous cell carcinoma of the tonsil. The case demonstrated the added value of 68 Ga-FAPI-46 PET/CT for locating the primary malignancy in cancer of unknown primary.
Endoscopic submucosal dissection of a rectal lesion using a new flower-shaped multiband traction system
Authors: Fausto Riu Pons, Marta Antón Arnal, Miguel Angel Pantaleón Sanchez, Marc Batlle Garcia, Agustín Seoane Urgorri, Xavier Bessa Caserras, Luis Barranco Priego
Journal: Endoscopy (2025)