CLEVER: Clinical Large Language Model Evaluation by Expert Review (Preprint)

Опубликована: Фев. 4, 2025

The proliferation of both general-purpose and healthcare-specific Large Language Models (LLMs) has intensified the challenge effectively evaluating comparing them. Data contamination plagues validity public benchmarks; self-preference distorts LLM-as-a-judge approaches; there’s a gap between tasks used to test models those in clinical practice. In response, we propose CLEVER: A methodology for blind, randomized, preference-based evaluation by practicing medical doctors on specific tasks. We demonstrate GPT-4o against two LLMs, with 8B 70B parameters, over three tasks: text summarization, information extraction, question answering biomedical research. Medical prefer Small LLM 45% 92% more often dimensions factuality, relevance, conciseness. show comparable performance open-ended Q&A, suggesting that LLMs can outperform much larger require understanding context. CLEVER evaluations conducting inter-annotator agreement, inter-class correlation, washout period analysis. n/a

Язык: Английский

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Metastatic Head and Neck Cancer: Immunotherapy and Beyond

Seminars in Radiation Oncology, Год журнала: 2025, Номер 35(2), С. 259 - 270

Опубликована: Март 14, 2025

Head and neck cancer is estimated to result in 71,000 new diagnoses 16,000 deaths 2024. Of these cases, approximately 14% will be metastatic. Recent changes treatment paradigms have established immunotherapy as a cornerstone of the metastatic recurrent setting. While has undoubtedly improved outcomes can lead long term durable responses select patients, overall response rates remain suboptimal, with 13%-20% patients responding most studies. This review aims provide an overview current landscape immunotherapies head malignancies. Additionally, we aim discuss future immunotherapy, well novel targets therapeutic platforms that may continue change paradigm this disease.

Язык: Английский

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UV1 vaccination in pembrolizumab-treated patients with recurrent or metastatic head and neck cancer: A randomized multicenter phase 2 trial

Med, Год журнала: 2025, Номер unknown, С. 100647 - 100647

Опубликована: Апрель 1, 2025

Язык: Английский

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Breaking Ground in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Novel Therapies Beyond PD-L1 Immunotherapy

American Society of Clinical Oncology Educational Book, Год журнала: 2024, Номер 44(3)

Опубликована: Май 8, 2024

The treatment for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors (anti-PD1) or without chemotherapy has led to an improvement in survival. Yet, despite this therapeutic advancement, only 15%-19% of patients remain alive at four years, highlighting the poor survival unmet need improved therapies patient population. Some key evolving novel therapeutics beyond anti-PD1 R/M HNSCC have included vaccine therapies, bispecific antibodies/fusion proteins multitargeted kinase inhibitors, antibody-drug conjugates (ADCs). Multiple concurrent investigations anti-PD(L)1 inhibition are currently underway some promising early results. Beyond inhibition, immunotherapeutic strategies including vaccines ranging from targeting human papillomavirus-specific epitopes personalized neoantigen ongoing efficacy signals large, randomized trials. Other weapons antibodies, fusion proteins, leverage multiple targets modulation tumor microenvironment harness antitumor immunity protumorigenic signaling pathways emerging Finally, as other solid tumors, ADCs a intervention either alone combination immunotherapy HNSCC. With enthusiasm across HNSCC, results larger trials eagerly awaited.

Язык: Английский

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UV1 cancer vaccine in pembrolizumab-treated patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma: results from the randomized phase 2 FOCUS trial

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 24, 2024

Abstract Background Human telomerase reverse transcriptase (hTERT) is highly expressed (75-100%) in head and neck squamous cell carcinoma (HNSCC). The FOCUS study examines the role of hTERT-directed vaccine UV1 combination with pembrolizumab patients recurrent or metastatic (R/M) HNSCC. Methods trial, a two-armed, open-label, non-comparative, randomized, multicenter phase 2 study, was designed to assess efficacy feasibility as an add-on first-line treatment R/M PD-L1 positive A progression-free survival rate at 6 months (PFSR@6) 40% deemed promising for further development 3 setting. trial conducted 10 centers Germany. Results From August 2021 July 2023, 25 were enrolled calibration arm 50 B. Median age 65 years 18% had ECOG performance score 2. PFSR@6 30% arm. No specific safety signals observed apart from reversible allergic reaction that appeared one patient. At median follow-up almost year (11.3 months), overall 13.1 12.6 Clinical identification number NCT05075122 . Conclusions addition safe but did not show signal this population.

Язык: Английский

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Head and neck cancer care: advanced molecular and genetic diagnostics.

PubMed, Год журнала: 2024, Номер 23, С. 1229 - 1231

Опубликована: Янв. 1, 2024

Язык: Английский

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Preclinical in vitro models of HNSCC and their role in drug discovery - an emphasis on the cancer microenvironment and microbiota

Expert Opinion on Drug Discovery, Год журнала: 2024, Номер unknown, С. 1 - 21

Опубликована: Дек. 15, 2024

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide. Treatment options patient outcomes have not improved significantly over past decades, increasing need for better preclinical models. Holistic approaches that include an intact functional immune compartment along with patient's individual tumor microbiome will help improve predictive value of novel drug efficacy.

Язык: Английский

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