The clinical efficacy and immune modulation of neoadjuvant immunochemotherapy for epithelial ovarian cancer (EOC) remain uncertain. To clarify these effects, the NAIVE trial (NCT04815408), a prospective phase II study, evaluated the efficacy of neoadjuvant platinum-based chemotherapy with tislelizumab (NACI) in comparison with chemotherapy alone (NAC) in patients with FIGO IIIC-IV EOC. The primary endpoint was the 1-year progression-free survival (PFS) rate; the secondary endpoints included PFS, R0 resection, clinical and pathological responses, and safety. Between April 2021 and July 2024, 25 patients were included in the final analysis. After a median follow-up period of 30.7 months, NACI was associated with numerically prolonged progression-free survival (27.2 vs. 21.8 months; HR = 0.44, 95% CI 0.15-1.26; P = 0.127), with higher 1-year (92.3% vs. 83.3%) and 2-year (62.3% vs. 31.8%) PFS rates than NAC. NACI also yielded superior tumor responses, including higher ORR (69.2% vs. 58.3%), more R0 resections, and increased CRS3 rates. No unexpected safety signals emerged, and immune-related adverse events were manageable. Immune profiling techniques, such as single-cell RNA sequencing and CyTOF, identified distinct signatures. NACI responders demonstrated heightened CD8⁺ T-cell-mediated toxicity and metabolic fitness, whereas nonresponders exhibited exhaustion phenotypes. Furthermore, the response correlated with enrichment of the CXCL13⁺Th1-GC B-cell-tertiary lymphoid structure (TLS) axis, accompanied by increased TLS activity and differentiation to IgG-producing plasma cells. Overall, NACI yielded PFS trends with acceptable safety, but without statistical significance. The mechanistic analyses highlight the role of the CXCL13⁺Th1-GC B-cell-TLS axis as a potential biomarker and driver of therapeutic response.

Intraductal papillary mucinous neoplasm (IPMN) is a well-recognized precursor of pancreatic cancer; however, the optimal surveillance strategy for IPMN remains controversial. This study aimed to evaluate the clinical impact of semiannual surveillance using endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) for the detection of malignant transformation, including IPMN-derived and concomitant carcinoma.

This multicenter prospective observational study included 360 patients with branch-duct or mixed-type IPMN enrolled between April 2018 and December 2025. Patients underwent surveillance every 6 months with blood tests and EUS or MRI. The primary endpoint was the curative resection rate among patients diagnosed with IPMN-derived or concomitant carcinoma. Secondary endpoints included the incidence of newly developed worrisome features (WF) and high-risk stigmata (HRS), as well as the cumulative incidence of malignancy.

During a median follow-up period of 69 months, newly developed WF and HRS were observed in 30.3% and 2.5% of patients, respectively. Malignant transformation was confirmed in 12 patients (3.3%), including nine with IPMN-concomitant carcinoma and three with IPMN-derived carcinoma. Curative resection was performed in 9 of these patients, resulting in a surgical transition rate of 75.0%. All malignant pancreatic lesions were detected at a resectable or borderline-resectable stage at diagnosis.

Semiannual surveillance using EUS and MRI facilitated the detection of malignant pancreatic lesions at a surgically treatable stage in patients with IPMN. This surveillance strategy may be clinically valuable for identifying IPMN-derived and concomitant carcinoma at stages amenable to surgical treatment in high-risk populations.

Over the past decades, both hypofractionation and (focal) dose escalation have been studied in trials for prostate cancer (PCa) radiotherapy. Several studies have demonstrated a benefit of dose escalation in terms of improved biochemical progression-free survival (bPFS). Whole-gland dose escalation, however, is associated with an increased risk of side effects. The concept of isotolerated focal boosting was tested in the phase III FLAME trial and showed improved bPFS survival in patients with intermediate- and (mainly) high-risk PCa, without significantly increasing side effects. Following this publication, a steady increase in the number of patients treated with focal boosting of the intraprostatic tumour(s) is anticipated. Thus, the current ESTRO recommendation has been developed to provide practical suggestions for the implementation of focal boosting of the intraprostatic tumour(s). We here present an overview of the existing literature and, based on evaluation of the current evidence and expert opinion, we formulate a set of practical 'how-to' recommendations to support the integration of focal boosting of the intraprostatic tumour(s) using either external beam radiotherapy or brachytherapy into routine clinical practice.

Autoimmune encephalitis (AE) is a disorder in which the immune system targets the central nervous system. AE can be paraneoplastic or postinfectious, though many cases lack a clear trigger. AE typically presents acutely or subacutely with altered mental status and psychiatric symptoms, with clinical features varying by the targeted autoantigen. MR imaging is the imaging modality of choice and may show T2 and fluid attenuation inversion recovery (FLAIR) hyperintensities in the medial temporal lobes, characteristic of limbic encephalitis, though imaging can be normal or may extend beyond the limbic system. Key differentials include infectious encephalitis and tumors.

The current landscape of extensive-stage SCLC treatment is dynamic, with exciting active agents including bispecific T-cell engagers, antibody-drug conjugates, and novel combinations. The foundation of SCLC frontline treatment is platinum-etoposide doublet plus anti-PD-L1 inhibitor, but most patients will develop refractory disease. Identifying effective treatments with manageable toxicity remains a major unmet clinical need. The study by Ponce et al, entitled "Combination of Lurbinectedin Plus Irinotecan: Preclinical and Early Clinical Results in Relapsed Small Cell Lung Cancer Patients," made significant contributions to the field. This study revealed that lurbinectedin and irinotecan induced synergistic antitumor activity in specific molecular subtypes of SCLC in preclinical models and then tested this combination in a phase I-II dose-escalation study in 26 patients with relapsed SCLC. This commentary will discuss how this work highlighted several impactful themes in SCLC: (1) innovative use of patient-derived xenografts; (2) synergistic combinations; (3) optimal sequencing of therapies; and (4) appropriate patient selection including the potential for biomarker-directed option for neuroendocrine subtypes.

Since the launch of the Journal of Thoracic Oncology in 2006, interventional radiology has evolved from a predominantly palliative adjunct into a core component of multidisciplinary thoracic oncology. Advances in imaging, device engineering, and procedural techniques have expanded its role across diagnosis, treatment, and symptom control in lung cancer, pleural mesothelioma, and other intrathoracic malignancies. This review summarizes two decades of progress and clinical practice in interventional thoracic oncology.

A narrative review of the published literature from 2006 to 2026 was performed, focusing on image-guided diagnostic techniques, percutaneous and endovascular therapies, pleural interventions, and emerging technologies relevant to thoracic malignancies. Emphasis was placed on clinical outcomes, safety, patient-centered considerations, and integration within multidisciplinary care pathways.

Image-guided biopsy techniques have progressed from fluoroscopic guidance to computed tomography based, navigational, and robotic approaches, achieving high diagnostic accuracy with progressively lower complication rates. Percutaneous thermal ablation techniques, including radiofrequency, microwave, and cryoablation, provide effective local tumor control for selected patients with early stage or oligometastatic lung cancer who are not surgical candidates, with favorable survival and morbidity profiles. Endovascular interventions, such as bronchial artery embolization and chemoembolization, offer important therapeutic options for hemoptysis and advanced disease. In pleural mesothelioma, interventional radiology underpins diagnosis, effusion management, and emerging locoregional therapies. Improvements in safety, outpatient feasibility, and patient experience have been substantial.

Interventional radiology has become indispensable in thoracic oncology, spanning diagnosis, definitive and palliative treatments, and supportive care. Ongoing advances in artificial intelligence, robotics, and precision oncology are likely to further expand its clinical impact.

Fibroblast activating protein (FAP) expressing fibroblasts are an attractive target for cancer therapeutic depletion and while preclinical depletion shows success, previous modalities have had unsuccessful clinical impact. Here, we wanted to comprehensively understand the tumor microenvironmental changes after FAP⁺ fibroblast depletion and unravel potential reasons for resistance and vulnerabilities that appear upon treatment with a FAP-targeted T-cell engager. To unveil the complex changes that occur in the tumor microenvironment (TME) after FAP⁺ fibroblast depletion, we generated comprehensive single-cell RNA-sequencing analysis of FAP⁺ cancer-associated fibroblasts (CAFs) depletion within the TME to understand the key populations and genetic modulations in all cell subtypes.

A CD3 T-cell engager directed against FAP (FAP TcE) was used to deplete FAP⁺ fibroblasts in a preclinical murine model of pancreatic cancer. To understand complex population dynamics on FAP TcE, we performed single-cell RNA-sequencing of treated versus untreated tumors to unveil population and genetic changes.

Administration of FAP TcE resulted in tumor growth control in vivo that was not dependent on T-cell priming and egress via draining lymph nodes. After FAP TcE, T-cell exhaustion was prevalent with an increased T-cell exhaustive state and the emergence of a T-cell progenitor exhausted state, yet the addition of anti-programmed cell death protein 1 (PD-1) failed to enhance tumor efficacy. Within fibroblast populations, FAP TcE depleted FAP⁺ CAFs; however, depletion is compensated by an emergence of a "mixed CAF" population, potentially limiting the efficacy of FAP TcE.

This study highlights the complex and plastic fibroblast changes occurring with stroma-targeted therapies that may limit therapeutic efficacy.

Somatic mutations involving the canonical exon 10 hotspots of the thrombopoietin receptor gene (MPL) are established drivers in myeloproliferative neoplasms (MPNs), whereas the significance of rare, atypical variants remain unclear. We investigated the relevance of three uncommon MPL variants affecting residues Y591 and R592. Among a multicenter cohort with myeloid neoplasms undergoing next-generation sequencing (NGS), eight individuals harbouring MPL p.Y591D, p.Y591H, or p.R592Q variants were identified. Clinical data were integrated with a comprehensive literature review, in silico pathogenicity prediction, and structural bioinformatics modelling of the MPL-JAK2 complex. Clinically, these variants were observed across heterogeneous myeloid disorders and consistently co-occurred with canonical driver mutations in MPN cases. Certain patients with Y591 substitutions seem to exhibit aggressive disease phenotypes and/or suboptimal responses to JAK-inhibitors, whereas R592Q cases showed variable outcomes influenced by co-mutational profiles. Computational predictors yielded discordant pathogenicity assessments. Structural modeling indicated that these substitutions induce minor local rearrangement and do not significantly disrupt the overall MPL-JAK2 complex assembly. However, the Y591 substitutions may lead to loss of critical regulatory motifs by removing a key phosphorylation-dependent docking site and disrupting the YXXφ motif, potentially leading to receptor hypersensitivity to thrombopoietin. Regarding pathogenicity classification, the p.R592Q substitution should be considered as a variant of uncertain significance (VUS), whereas the Y591 alterations may be categorized either as VUS or as "likely oncogenic" depending on the chosen framework. Crucially, current evidence indicates that MPL p.Y591D, p.Y591H, and p.R592Q variants do not act as primary oncogenic drivers but may function only as disease modifiers.

Accurate prognostic assessment is crucial for guiding clinical decisions in meningioma patients. Traditional prognostic indexes have been limited by subjectivity, oversimplification, or lack of specific validation for meningiomas, leading to inaccuracies from misaligned scaling objectives. This study aimed to create a refined weighting system, integrating variables from prior indexes to better reflect prognostic significance in meningioma patients.

The authors retrospectively analyzed the data of 592 patients who underwent intracranial meningioma resection at a single institution (2009-2024). The primary endpoint was lack of functional independence at 6 weeks (modified Rankin Scale [mRS] score ≥ 3). Univariable screening and multivariable logistic regression identified independent predictors, which were translated into a simplified point-based system: Meningioma Functional Outcome Risk and Counseling Estimator (M-FORCE) 6 score. Internal validation was performed using 10,000 bootstrap resamples. Discrimination, calibration, and clinical utility (decision curve analysis) were assessed.

Skull base origin (OR 2.21), infratentorial location (OR 2.12), preoperative dependence (mRS score > 2, OR 2.27), tumor size ≥ 40 mm (OR 3.06), and comorbidity burden (Charlson Comorbidity Index [CCI] score > 2, OR 2.41; CCI score > 6, OR 2.46) independently predicted functional dependence at 6 weeks. These variables were incorporated into the M-FORCE 6 score. Patients were stratified into four risk groups: low (0-3 points, 6.2% risk), intermediate (4-6 points, 26.5% risk), high (7-9 points, 46.9% risk), and very high (10-13 points, 71.4% risk). The optimism-corrected areas under the curve of the multivariable model and the score were both 0.76, with excellent calibration and favorable net benefit on decision curve analysis.

The M-FORCE 6 score provides a transparent, meningioma-specific tool for preoperative risk stratification, integrating demographic, clinical, and radiological features into a simple and reproducible model. External validation is warranted to confirm its generalizability.

The trend of homemade sunscreen recipes has rapidly gained popularity over the last decade, being largely fueled by social media influencers, natural health blogs, and the growing mistrust of large health organizations like the US Food and Drug Administration (FDA). Consumers are increasingly drawn to products labeled "natural," "organic," "vegan," and "cruelty-free," often conflating these terms with safety and effectiveness. However, when applied to sun protection, these assumptions can be dangerously misleading. According to the FDA, there is no verified mathematical formula that can be used to determine an accurate sun protection factor (SPF) rating for the amount of zinc oxide used in many of the recipes found online.

The objective of this review is to examine the rising popularity and efficacy of homemade sunscreens compared to commercial sunscreens and highlight the potential public health implications of skin cancer risk related to homemade sunscreen use.

Multiple databases were searched to find current and relevant literature analyzing the social media impact relating to homemade sunscreens and the efficacy of homemade sunscreens compared to commercially available products. Digital content that included or discussed homemade sunscreen recipes was included as well to provide examples of information trending online.

One study analyzing social media trends found that many strong, unverified claims relating to homemade sunscreen versus commercial sunscreen use are being presented in the media, potentially influencing public knowledge. Additional studies analyzing the components of homemade sunscreen recipes compared to components in commercially available products found that homemade sunscreens offer little to no sun protection, therefore increasing the risk of UV damage for individuals using homemade products.

Based on the presented evidence, the adoption of unregulated homemade sunscreens presents a substantial threat to public health. Misinformation spread through social media and influencer culture may unintentionally contribute to an increase in UV-related skin cancers. Greater efforts are needed from health care professionals, regulatory bodies, and online platforms to educate the public and promote the use of scientifically validated sun protection methods.