A Pooled Analysis of Datopotamab Deruxtecan in Patients With EGFR-Mutated NSCLC.

Background: This exploratory analysis assessed datopotamab deruxtecan (Dato-DXd) in pretreated patients with advanced or metastatic NSCLC and EGFR mutations.

Methods: Data were pooled from the phase II TROPION-Lung05 (NCT04484142) and phase III TROPION-Lung01 (NCT04656652) trials. Patients with EGFR-mutated advanced or metastatic NSCLC, who had received previous targeted therapies and platinum-based chemotherapy, received Dato-DXd 6 mg/kg (TROPION-Lung05) or were randomized to Dato-DXd 6 mg/kg or docetaxel 75 mg/m (TROPION-Lung01) once every 3 weeks.

Exploring new frontiers in LAG-3 biology and therapeutics.

Lymphocyte activation gene-3 (LAG-3) has emerged as a critical immune checkpoint receptor primarily modulating T-cell responses through distinct immune regulatory mechanisms. Recent advances have elucidated LAG-3's complex receptor-ligand interactions, structure-function relationships, and unique signaling pathways. LAG-3 antagonistic antibodies, such as relatlimab approved for melanoma, have shown promising efficacy with favorable toxicity profiles, though only in combinational therapies.

Importance of Prior Patient Interactions With the Healthcare System to Engaging With Pretest Cancer Genetic Services via Digital Health Tools Among Unaffected Primary Care Patients: Findings From the BRIDGE Trial.

Objective: To examine whether patient sociodemographic and clinical characteristics and prior interactions with the healthcare system were associated with opening patient portal messages related to cancer genetic services and beginning services.

Study Setting And Design: The trial was conducted in the University of Utah Health (UHealth) and NYU Langone Health (NYULH) systems. Between 2020 and 2023, 3073 eligible primary care patients aged 25-60 years meeting family history-based criteria for cancer genetic evaluation were randomized 1:1 to receive a patient portal message with a hyperlink to a pretest genetics education chatbot or information about scheduling a pretest standard of care (SOC) appointment.

Approaching an Undiagnosed Pleural Effusion.

Pleural effusions are commonly encountered in the practice of pulmonary medicine, and their clinical evaluation is usually straightforward. However, up to 20% of pleural effusions are not diagnosed despite clinical evaluation and pleural fluid analysis. Further investigation of the undiagnosed pleural effusion requires a systematic evaluation using clues from a patient's history, physical examination, imaging, and pleural fluid analysis help narrow down the differential diagnosis.

In-depth characterization of vaccine-induced neoantigen-specific T cells in patients with IDH1-mutant glioma undergoing personalized peptide vaccination.

Isocitrate dehydrogenase (IDH) mutant glioma is a malignant primary brain tumor diagnosed in adults. In recent years, there has been significant progress in understanding the molecular pathogenesis and biology of these tumors. The first targeted IDH-inhibitor was approved by the US Food and Drug Administration in August 2024 for grade 2 gliomas, in light of results of a phase III trial which showed significant advantages in progression-free survival.

Macrophages: sentinels, warriors, and healers.

Macrophages are versatile innate immune cells that act as sentinels, warriors, and healers in virtually every tissue. This review synthesizes current insights into their developmental origins and the organ-specific cues that imprint diverse tissue-resident and monocyte-derived programs. We detail how pattern-recognition pathways, metabolic and epigenetic rewiring, and environmental signals govern macrophage plasticity, steering transitions between pro-inflammatory and reparative phenotypes during homeostasis, infection, and sterile injury.

Inherited mitochondrial genetics as a predictor of immune checkpoint inhibition efficacy in melanoma.

Response to immune checkpoint inhibitors (ICIs) in metastatic melanoma (MM) varies among patients, and current baseline biomarkers predicting treatment outcomes are limited. As mitochondrial (MT) metabolism has emerged as an important regulator of host immune function, we explored the association of host MT genetics (MT haplogroups) with ICI efficacy in 1,225 ICI-treated patients with MM from the clinical trial CheckMate-067 and the International Germline Immuno-Oncology Melanoma Consortium. We discovered and validated significant associations of MT haplogroup T (HG-T) with resistance to anti-programmed cell death protein-1-based ICI (both single-agent and combination) and have shown that HG-T is independent from established tumor predictors.

Computationally integrating radiology and pathology image features for predicting treatment benefit and outcome in lung cancer.

Lung cancer, the leading cause of cancer-related deaths globally, includes non-small cell lung cancer (NSCLC) (85% of cases) and small cell lung cancer (SCLC) (13-15%). While accurate diagnosis and treatment selection are critical, the absence of reliable predictive or prognostic biomarkers remains a significant challenge. This study explored the combined use of radiomics from CT scans and pathomics from H&E slides in three contexts: (1) predicting disease recurrence in early-stage NSCLC, (2) predicting immunotherapy response in advanced-stage NSCLC, and (3) predicting chemotherapy response in SCLC.

Bladder filling dynamics during online adaptive prostate stereotactic body radiotherapy: Rationale for using an empty bladder workflow for treatment.

Purpose: To evaluate the degree and rate of bladder filling during magnetic resonance imaging-guided linear accelerator (MRL) prostate stereotactic body radiotherapy (SBRT), and to determine the association of degree of bladder filling with intra-fractional prostatic motion requiring positional shifts during therapy. The impact of bladder filling on post-treatment target and normal tissue dosimetry was also evaluated.

Methods: Sixty-two consecutive prostate SBRT patients treated on the MRL with an empty bladder and a five-fraction regimen were evaluated.

OVATION-2: A randomized phase I/II study evaluating the safety and efficacy of IMNN-001 (IL-12 gene therapy) with neo/adjuvant chemotherapy in patients newly-diagnosed with advanced epithelial ovarian cancer.

Objective: OVATION-2, a randomized, controlled, open label phase 1/2 study, evaluated the safety and efficacy of IMNN-001, an IL-12 immune gene therapy, with neo/adjuvant chemotherapy (N/ACT) compared to N/ACT in newly-diagnosed advanced epithelial ovarian cancer (EOC).

Methods: IMNN-001 is an immunotherapeutic nanoparticle comprising a DNA plasmid encoding the IL-12 gene encased in a lipopolymer. High-grade EOC patients were randomized 1:1 to carboplatin/paclitaxel IV every 21 days for 3 cycles, before and after interval debulking surgery (IDS) or to intraperitoneal (IP) IMNN-001, given weekly concurrently with chemotherapy for 8 weeks before and 9 weeks after IDS.

Impaired Decision-Making Capacity in a Patient With Oral Squamous Cell Carcinoma: Weighing the Benefits and Harms of Treatment Against Objection.

Impairment of medical decision-making capacity is common in acutely ill patients especially those with solid malignancies. Many of these patients lack advance directives and healthcare proxies leaving clinicians with unclear guidance on subsequent treatment decisions and few existing mechanisms to address this issue. We present a case of a 55-year-old man with recurrent oral squamous cell carcinoma who lacked decision-making capacity due to cognitive impairment.

Long-term Efficacy and Safety of Lifileucel Tumor-infiltrating Lymphocyte (TIL) Cell Therapy in Patients with Advanced Melanoma: A 5-year Analysis of the C-144-01 Study.

Patients with advanced melanoma resistant to immune checkpoint or BRAF/MEK inhibitors have treatment options with relatively low efficacy. Lifileucel, a one-time autologous tumor-infiltrating lymphocyte cell therapy, was approved in the US based on the pivotal C-144-01 study. A 5-year follow-up of the C-144-01 trial assessed the long-term efficacy and safety of lifileucel.

Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy.

Background: Tarlatamab, a bispecific delta-like ligand 3-directed T-cell engager immunotherapy, received accelerated approval for the treatment of patients with previously treated small-cell lung cancer. Whether tarlatamab is more effective than chemotherapy in the treatment of patients whose small-cell lung cancer has progressed during or after initial platinum-based chemotherapy is not known.

Methods: We conducted a multinational, phase 3, open-label trial to compare tarlatamab with chemotherapy as second-line treatment in patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy.

Zipalertinib in Patients With Epidermal Growth Factor Receptor Exon 20 Insertion-Positive Non-Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab.

Purpose: To evaluate the safety and efficacy of zipalertinib, an irreversible epidermal growth factor receptor (EGFR) inhibitor, in pretreated patients with non-small cell lung cancer (NSCLC) harboring exon 20 insertion (ex20ins) mutations.

Methods: REZILIENT1 (ClinicalTrials.gov identifier: NCT04036682) is a phase I/II open-label trial enrolling patients with locally advanced or metastatic ex20ins-mutant NSCLC previously treated with platinum-based chemotherapy with/without ex20ins-targeted therapies.

A phase 0, window of opportunity study of parasympathetic stimulation with bethanechol in localized pancreatic adenocarcinoma prior to surgery.

Background: The parasympathetic branch of the autonomic nervous system has shown tumor-suppressive effects in preclinical models of pancreatic adenocarcinoma (PDAC) by inhibiting cancer stem cells and suppressing inflammatory cytokine production. Based on these findings, we hypothesized that bethanechol, an FDA-approved parasympathomimetic agent targeting muscarinic receptors, could enhance treatment efficacy in PDAC.

Methods: We conducted a phase 0/window of opportunity study evaluating short-term parasympathetic activation with fixed dose bethanechol (100 mg twice daily) in subjects with resectable or borderline resectable PDAC prior to surgery.

Clinical, molecular and radiological predictors of prognosis in newly diagnosed astrocytoma, IDH-mutant, WHO grade 4.

Background: Astrocytoma, isocitrate dehydrogenase-mutant, WHO grade 4 (Astro4), is a new tumor type in the 2021 WHO classification of central nervous system tumors that has been poorly characterized in the literature. This study evaluates predictors of prognosis in a large cohort of newly diagnosed Astro4.

Methods: We retrospectively identified 128 consecutive adult patients who presented with an initial diagnosis of Astro4 at Dana-Farber Cancer Institute and Massachusetts General Hospital between 2010 and 2021.

Molecular determinants of sotorasib clinical efficacy in KRAS-mutated non-small-cell lung cancer.

Molecular determinants of KRAS(G12C)inhibitor efficacy in KRAS-mutated non-small-cell lung cancer (NSCLC) remain poorly characterized. Here we report one of the largest integrated analyses to date of sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 studies. We reveal differential sotorasib activity and relative benefit compared to docetaxel across KRAS-mutated NSCLC co-mutational subsets and transcriptional subtypes.

Postoperative radiotherapy in subtotally-resected recurrent WHO grade 1 meningiomas with intermediate-/high-risk molecular profiles.

Background: Meningiomas represent the most common primary intracranial tumors in adults, with WHO grade 1 typically associated with favorable outcomes following gross total resection (GTR).

Methods: This retrospective study included patients with CNS WHO grade 1 meningioma and available DNA methylation profiles (n=210). Clinical tumor characteristics and treatment course (e.

MDM2 as a therapeutic target in advanced biliary tract cancers.

Biliary tract cancers (BTCs) are a heterogeneous group of tumors arising from cells in the bile ducts and gallbladder. The 5-year overall survival rate for all BTC stages combined is ~20%, and treatment options for patients with unresectable disease are limited, leaving an unmet clinical need. In recent years, significant efforts have been made to refine and implement targeted therapeutic approaches for patients with BTC.

E-VIRTUE: a study of enfortumab vedotin with or without pembrolizumab in rare genitourinary tumors-design and rationale.

NCT06041503 (ClinicalTrials.gov).

Empowering stroke recovery with upper limb rehabilitation monitoring using TinyML based heterogeneous classifiers.

Stroke is one of the leading causes of disability worldwide, with approximately 70% of survivors experiencing motor impairments in the upper limbs, significantly affecting their quality of life. Home-based rehabilitation offers a cost-effective approach to improving motor function, but it faces challenges, including inaccurate movement reporting, lack of real-time feedback, and the high cost of rehabilitation equipment. Therefore, there is a need for affordable, lightweight home-based rehabilitation monitoring systems.

Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia.

Isocitrate dehydrogenase 1/2 (IDH) mutations are early initiating events in acute myeloid leukemia (AML). The complex clonal architecture and cellular heterogeneity in IDH-mutant AML underlies the heterogeneous clinical presentation and outcomes. Integrating single-cell genotyping and transcriptomics, we demonstrate a stem-like and inflammatory phenotype of IDH-mutant AML and identify clone-specific programs associated with NPM1, NRAS, and SRSF2 co-mutations.

Primary Mental Health Competencies for Hospice and Palliative Medicine Physicians: A Delphi Study.

Context: Psychiatric and psychological care in serious illness is a core domain of hospice and palliative medicine (HPM), encompassing both normative psychosocial responses and mental health comorbidities. While social workers serve as psychosocial leaders on HPM interdisciplinary teams, commitment to supporting whole-person care remains the responsibility of the entire team. However, training and scope of practice for HPM physicians in the mental health domain are poorly standardized.