BACKGROUND: [Lu]Lu-PSMA-617 has been an approved treatment modality for metastatic castration-resistant prostate cancer (mCRPC). Recent studies have shown PSMA upregulation following enzalutamide, which may enhance the outcomes with [Lu]Lu-PSMA-617. This study aims to evaluate the efficacy and safety of short-course enzalutamide priming with [Lu]Lu-PSMA-617 in mCRPC patients. METHODS: This investigator-initiated, single-arm phase 2 trial recruited men with mCRPC, having progressed on ≥one line of taxane and androgen-receptor pathway inhibitors (ARPIs), and fit for [Lu]Lu-PSMA-617. Enzalutamide (160 mg/day) was administered orally for 7 days before and after [Lu]Lu-PSMA-617 (7.4 GBq/cycle, up to 6 cycles, at 6-8 week intervals). The primary end-point was proportion of patients achieving ≥ 50% decline in prostate-specific antigen (PSA50-response rate, PSA50-RR). A sample size of 20 patients was calculated using Simon's two-stage design with at least 12/20 PSA50-responses required for rejection of null hypothesis. Secondary end-points included objective radiographic response rate (ORR), PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS), overall survival (OS), and adverse events (AEs). RESULTS: Between May 2023 and January 2025, 20 mCRPC patients (median age 67 years) were enrolled. The PSA50-RR was 40% (8/20, 95% CI: 19-64), thus the null hypothesis was not rejected. The ORR was 25% (5/20, 95% CI: 10-49). Over a median follow-up of 24 months, median PSA-PFS, rPFS, and OS were 4.0 months (95% CI: 3.0-7.5), 4.0 months (95% CI: 4.0-7.5), and 12.6 months (95% CI: 6.2-17.0), respectively. Grade 3 AEs were observed in four patients (20%, 95% CI: 6-44). CONCLUSION: The addition of short-course enzalutamide to [Lu]Lu-PSMA-617 did not meaningfully improve treatment outcomes of taxane and ARPI-exposed mCRPC patients in this trial. TRIAL REGISTRATION: Clinical Trials Registry-India, CTRI/2023/05/053301. Registered 31 May 2023.

BACKGROUND: Intermediate-risk prostate cancer (IR-PCa) is a heterogeneous disease with variable clinical outcomes despite established risk classification. We evaluated whether pretreatment tumor apparent diffusion coefficient (ADC) derived from multiparametric MRI was associated with long-term outcomes and provided additional prognostic information beyond established clinical risk classification in patients treated with definitive radiotherapy. METHODS AND MATERIALS: We retrospectively analyzed 238 patients with IR-PCa treated with definitive radiotherapy. Tumor ADC values were obtained from pre-treatment diffusion-weighted MRI. Patients were stratified according to ADC levels and clinical risk subgroups, including favorable and unfavorable intermediate-risk disease. Survival analyses and Cox regression models were used to assess associations between ADC and clinical outcomes, including biochemical failure and distant metastasis. RESULTS: At a median follow-up of 10.3 years, 22 patients developed biochemical failure, and 12 developed distant metastases. Lower ADC values (≤ 0.668 × 10mm/s) were associated with inferior outcomes, with a significant impact on freedom from distant metastasis (FFDM) (HR 3.94, 95% CI 1.14-13.62; p = 0.03). When ADC was combined with clinical risk classification, outcomes differed across the four resulting subgroups for both FFDM (p = 0.02) and FFBF (p = 0.02). However, the FIR-low ADC subgroup included only seven patients, and these subgroup findings should be considered exploratory. CONCLUSIONS: Lower tumor ADC was associated with an increased risk of distant metastasis and provided exploratory prognostic information beyond established clinical risk classification. Given the limited number of events and the data-derived cutoff, these findings require external validation before ADC can be used to guide treatment selection.

Cell division is an essential process required to maintain homeostasis. It must be tightly coordinated to allow the faithful transmission of the genetic material, and its regulation involves numerous partners. While some of them are well-characterized (e.g. Cyclin-Dependent Kinases, Aurora Kinases, …), others are still poorly understood. Citron Kinase (CitK) plays key roles during mitosis and cytokinesis, although its functions remain to be fully elucidated. In addition, its roles are not restricted to cytokinesis, and CitK also comes into play at earlier stages of cell division. Furthermore, emerging evidence suggests a role for CitK during tumorigenesis. Several studies have pointed to the potential of targeting CitK in the context of cancer treatment and hopefully this will bring attention to this largely understudied kinase. This review focuses on the different functions of Citron Kinase throughout the cell cycle to highlight its importance during cell division as well as its significance in cancer and its potential as a target for cancer therapy.

INTRODUCTION: The incidence of thyroid cancer has risen significantly worldwide over the past two decades, while mortality rates have remained stable. Early detection and modern treatment protocols are keys to improving patient survival. OBJECTIVE: The primary objective of our study was to map domestic diagnostic and therapeutic practices in differentiated thyroid cancer. Our secondary objectives were to develop background material for national clinical protocols. METHOD: The retrospective study focused on the clinical data of patients diagnosed with thyroid cancer between 2011 and 2024. As there were no exclusion criteria, the results provided a representative picture of current diagnostic and therapeutic practices in Hungary. RESULTS: We analyzed data of 893 patients (75.7% female, 24.3% male). The mean age of the study population was 53.1 ± 14.8 years. Differentiated thyroid cancers were predominant, with the papillary subtype accounting for 82.8% of cases. Most patients (63.5%) were diagnosed at an early stage (T1a-T1b); regional lymph node involvement occurred in 34%, and distant metastasis in 4.7%. Most patients underwent a single surgical procedure; the majority (80.8%) underwent total or near-total thyroidectomy. Procedures targeting regional lymph nodes were common, while radical neck dissection was less frequent, which is consistent with the typical locoregional spread of differentiated thyroid cancer and modern, targeted surgical strategies. Patients receiving radioiodine therapy underwent treatment an average of 1.41 times. Individual radioiodine doses varied significantly, with an average dose of 2,645 MBq, while the range of cumulative doses administered extended from 1,100 MBq to 11,000 MBq. The TSH-suppressive levothyroxine treatment was administered to 57.7% of patients. Systemic therapy was rarely used (in 3.2% of cases). DISCUSSION: The study indicates that diagnostic and therapeutic practices in the management of thyroid cancer in Hungary are in accordance with international standards. CONCLUSION: The study provided a comprehensive overview of the demographic, histological, and treatment characteristics of thyroid cancer patients in Hungary. The results may serve as a basis for further clinical research and follow-up analyses, facilitating the long-term optimization of thyroid cancer treatment and improving patient prognosis. Orv Hetil. 2026; 167(37): 1468-1476.

INTRODUCTION: Oncology tumor boards are key elements in the management of cancer patients. Registration of the patients presented at the tumor boards allows the evaluation of the activity of the working group. METHOD: Patients presented at the uro-oncology tumor board of the Petz Aladár Hospital were registered in the period between 2017 and 2024. Longitudinal patient flow data are analysed in the present manuscript. RESULTS: The number of patients treated for localized prostate, bladder and kidney cancer was increasing step by step, while the incidence of metastatic diseases was decreasing in parallel for prostate and bladder cancer and stable for kidney cancer. The ratio of metastatic to early diseases decreased from 1 : 1.2 to 1 : 4.6 for prostate cancer, from 1 : 3.0 to 1 : 5.4 for bladder cancer and from 1 : 5.4 to 1 : 6.7 for kidney cancer. At the end of the period, there were two years when less than yearly five metastatic bladder cancer patients were lost in our hospital. CONCLUSION: The increasing number of patients managed for localized diseases as well as the decreasing ratio of patients managed for metastatic diseases are both indicators of good quality care. Orv Hetil. 2026; 167(37): 1477-1482.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurotoxicity of cancer treatment with limited diagnostic, monitoring, and treatment options. Neurofilament light chain (NfL) is an axonal cytoskeletal protein released during neuroaxonal injury and a promising biomarker of CIPN, but prospective evidence for NfL as a marker of CIPN from vincristine-containing lymphoma chemotherapy treatment remains limited. To fill this gap, we conducted a pragmatic single-center prospective observational cohort study of adults with non-Hodgkin lymphoma (NHL) receiving first-line vincristine-containing chemotherapy to evaluate NfL dynamics across multiple pre-cycle visits and assess relationships with patient-reported and clinician-graded neuropathy measures. We followed 25 participants during 4-6 months of chemotherapy, and a small subset of those participants (n=6) for 24-42 months post-chemotherapy. Serial plasma NfL was measured and CIPN symptoms were assessed using patient- and clinician-reported measures. Longitudinal changes were analyzed using mixed-effects models. Plasma NfL increased relative to pre-cycle1 at all timepoints (all p<0.001), increasing approximately fourfold by pre-cycle4. Patient-reported CIPN scores and clinician-graded neuropathy also increased during treatment. Exploratory pooled visit-level analyses showed a modest NfL-CIPN association (repeated measures correlation=0.439, p=0.020), while timepoint-specific, lagged, and post hoc sensitivity analyses suggested potential to predict persistent CIPN symptoms from early NfL concentrations. To our knowledge, these findings extend prospective evidence supporting NfL as a biomarker of vincristine exposure in adults with NHL receiving vincristine-containing therapy and may complement patient-reported symptom assessment, clinician grading, and dose-modification context in future CIPN monitoring studies.

BACKGROUND: Aplastic anaemia (AA) and paroxysmal nocturnal haemoglobinuria (PNH) are closely related acquired bone marrow failure syndromes sharing an immune-mediated pathogenesis. Cytogenetic abnormalities are uncommon in AA-PNH overlap syndrome, and their significance remains uncertain. We report a case of non-severe AA-PNH overlap syndrome harbouring a low-level chromosome 17p deletion in the absence of morphologic or molecular evidence of myeloid neoplasm. CASE PRESENTATION: A 56-year-old female presented with recurrent aphthous ulcers and pancytopenia. Complete blood count revealed haemoglobin of 6.3 g/dL, total leukocyte count of 2800/µL with an absolute neutrophil count of 982/µL, and platelet count of 10,000/µL. Bone marrow aspirate showed adequate erythropoiesis with normoblastic to megaloblastic maturation and active myelopoiesis. Bone marrow biopsy revealed a markedly hypocellular marrow (10% cellularity) with focal erythroid prominence. No dysplasia, excess blasts, ring sideroblasts, and abnormal topography were identified. Flow cytometric PNH evaluation demonstrated a large type III clone involving 78% of neutrophils and 64% of monocytes. FISH analysis using TP53/CEP17 probes revealed chromosome 17p deletion in 12 of 200 nuclei (6%). Next-generation sequencing did not identify TP53 or other myeloid-associated mutations. The patient was treated with horse anti-thymocyte globulin, cyclosporine, romiplostim, erythropoietin, and irradiated blood products. She achieved transfusion independence and remains clinically stable on follow-up of 27 months. CONCLUSION: Low-level chromosome 17p deletion may occur in AA-PNH overlap syndrome without morphologic or molecular evidence of myeloid neoplasm. Careful clinicopathologic correlation and long-term surveillance are essential before attributing such abnormalities to clonal evolution.

PURPOSE: To describe a lower detrusor apron-sparing (LDAS) modification of robot-assisted radical prostatectomy (RARP) adapting anterior-compartment preservation to side-specific oncological risk, and report perioperative, functional and oncological outcomes. METHODS: We retrospectively analysed a prospectively maintained, single-surgeon cohort of 167 men with localised prostate cancer undergoing RARP with unilateral or bilateral LDAS nerve-sparing (2019-2025). On the LDAS side the lower detrusor apron and anterior periurethral support were preserved without opening the endopelvic fascia, with conventional dissection contralaterally when risk was higher. Patient-reported outcomes were collected electronically. Continence was defined as 0-1 safety pad/24 h (strict, 0 pad), erectile recovery as penetrative intercourse with or without phosphodiesterase-5 inhibitors, and biochemical recurrence (BCR) as two consecutive PSA values ≥ 0.2 ng/mL. RESULTS: Clavien-Dindo ≥ III complications occurred in 1.2%; mean stay 0.6 days (46% same-day discharge). Continence (0-1 pad) was 85%, 97%, 99% and 100% at 6 weeks, 6, 12 and 24 months; strict (0-pad) continence was 51%, 84%, 92% and 97%. Intercourse capability reached 71% at 12 months. Outcomes did not differ by LDAS laterality. Positive surgical margins (PSM) occurred in 16% overall and 8.2% of LDAS-preserved sides. Over a median follow-up of 37 months (IQR 19-55), BCR-free survival rates were 99%, 96%, 94% and 89% at 1, 2, 3 and 5 years; BCR did not differ by LDAS-side PSM status (p = 0.7). CONCLUSION: Side-specific LDAS RARP was associated with rapid continence recovery, low morbidity and favourable mid-term oncological outcomes. Lacking a contemporaneous comparator, these single-surgeon findings are hypothesis-generating and require prospective, multicentre, comparative validation.

BACKGROUND AND OBJECTIVE: Malnutrition in cancer patients is a complex and multifactorial condition. Validated nutritional screening instruments are essential to ensure diagnostic, accuracy and guide effective nutritional interventions. This study aimed to validate the NUTRISCORE instrument in cancer patients undergoing outpatient treatment. MATERIALS AND METHODS: This cross-sectional observational study included 194 patients with neoplasia receiving outpatient care. Clinical data (tumor location, treatment, metastasis, and palliative care) and nutritional information were collected through interviews and electronic medical records. Validation was performed using the Patient-Generated Subjective Global Assessment (PG-SGA) as the reference standard, calculating sensitivity, specificity, positive and negative predictive values (NPVs), area under the curve (AUC), and agreement using the Kappa coefficient (κ), with a 5% significance level. RESULTS: NUTRISCORE identified 47 patients (24.2%) at nutritional risk, whereas the PG-SGA classified 110 (56.7%). Leukemia, breast cancer, and colorectal cancer were the most frequent tumor types. NUTRISCORE showed 34.55% sensitivity, 89.29% specificity, AUC of 0.71, and Kappa agreement of 0.22. CONCLUSIONS: Despite high specificity, NUTRISCORE showed low sensitivity and weak agreement with PG-SGA, indicating it was not validated for this population. Factors as tumor location may contribute to non-indentification of nutritional risk by the tool.

Tyrosine kinase inhibitors (TKIs) improve survival for people with chronic myeloid leukemia (CML) but may cause adverse events (AEs) that impair quality of life (QoL). Adults with CML receiving first- or second-line TKI therapy in the United States (US) completed validated questionnaires to assess AEs (PRO-CTCAE), QoL (PROMIS Global Physical Health [GPH] and Global Mental Health [GMH]), and work productivity and activity impairment (WPAI:SHP). Of 271 participants, 76.4% experienced ≥1 AE (median 3 [range 014]), with the most common being fatigue (53.9%), pain (44.3%), and gastrointestinal symptoms (36.9%). Mean (SD) GPH and GMH T-scores were worse than general population averages (50) at 42.6 (7.0) and 44.4 (7.7), respectively. Mean (SD) activity impairment was 37.3% (24.6). Chronic AEs were associated with worse GPH/GMH T-scores and activity impairment ( < 0.05). The findings demonstrate the relationship between TKI-related AEs and QoL for US patients and the need for improved management strategies.

OBJECTIVE: This study investigated the efficacy of a prophylactic, home-based exercise program administered concomitantly with radiotherapy in patients with head and neck cancer to preserve swallowing function, postural alignment, and cervical range of motion, while assessing lymphedema safety. STUDY DESIGN: Randomized controlled trial. SETTING: Outpatient clinics of an academic university hospital. METHODS: Twenty-four patients undergoing radiotherapy for head and neck cancer were allocated to an exercise group (n = 12; receiving a swallowing, posture, range of motion, and strengthening protocol) or a control group (n = 12; receiving standard care). Baseline and postradiotherapy outcomes were assessed using the Swallowing Quality of Life questionnaire, photogrammetric posture analysis, digital goniometry for cervical mobility, and circumference measurements for lymphedema. RESULTS: Swallowing Quality of Life was maintained in the exercise group but deteriorated significantly in controls (P < .001). The exercise group significantly preserved neck lateral tilt compared to controls (P < .001). Furthermore, the intervention group demonstrated significant preservation of cervical flexion, extension, rotation, and lateral flexion (P < .05). Facial edema metrics increased slightly in both groups with no significant inter-group differences, confirming intervention safety (P > .05). High adherence rates were reported. CONCLUSION: A prophylactic, home-based exercise program is a safe and effective strategy to mitigate functional decline in patients undergoing radiotherapy. The intervention preserves swallowing, posture, and cervical mobility without exacerbating lymphedema, supporting early prehabilitation in oncological care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT07376213.

BackgroundThe use of carbon fiber-reinforced polyetheretherketone (CFR-PEEK) instrumentation in spinal surgery has emerged as an alternative to traditional titanium-based implants in recent years. This study aims to evaluate the use and performance of carbon fiber instrumentation in patients with primary spinal tumors focusing on adverse event (AE) risk, overall survival and oncologic outcomes.MethodsData were collected from the AO Spine Primary Tumor Research and Outcomes Network (PTRON), a multicenter international registry. The primary endpoint was the incidence of AEs, while secondary endpoints included the risk of developing at least one AE, overall survival, local tumor control, and disease progression.ResultsA total of 359 patients enrolled in the PTRON registry met the inclusion criteria and were included in the study. Among them, 84 receiving carbon fiber implants (23%), 243 titanium implants (68%), and 32 a combination of both (9%). Median follow-up times were 1.9 years (IQR: 0.4-3.0), 1.3 years (IQR: 0.5-2.4) and 1.1 years (IQR: 0.5-1.7), in the carbon fiber, titanium and combination groups, respectively. The estimated risk of having at least one postoperative AE, including construct failures with and without loss of correction, wound infection (deep or superficial), non-union and wound dehiscence, was statistically comparable between patients receiving carbon fiber, titanium or a combination of both carbon fiber and titanium implants ( > 0.05). Kaplan-Meier survival analyses and multivariable Cox proportional hazards models showed no significant differences in overall survival, recurrence-free survival, or progression-free survival between the implant groups.ConclusionCarbon fiber spinal implants demonstrate a comparable safety and oncologic profile to traditional titanium implants while allowing for improved tumor surveillance and easier radiation delivery.

Existential distress and demoralization are common among patients with advanced cancer and are associated with impaired psychological well-being, reduced quality of life and difficulties in end-of-life adjustment. Meaning-Centered Psychotherapy (MCP), grounded in Viktor Frankl's logotherapy, was developed to address these existential dimensions of suffering. This narrative review synthesizes evidence from randomized and controlled studies evaluating MCP in adults with advanced cancer and discusses its clinical relevance within supportive and palliative care. Across studies, MCP demonstrated consistent improvements in meaning in life and spiritual well-being, with more modest effects on depressive symptoms and variable effects on anxiety and global quality of life. The available evidence supports MCP as a feasible and clinically relevant intervention for addressing existential distress, demoralization and loss of meaning in advanced cancer. Future research should examine long-term outcomes and implementation within routine oncology care.

Adenoid cystic carcinoma (ACC) of the breast is a rare, typically triple-negative malignancy with an indolent course and a biphasic epithelial and myoepithelial histology that can be mistaken for benign or high-risk lesions on core needle biopsy. We describe a 52-year-old woman with two masses at the 4 o'clock position of the right breast, 5 cm and 7 cm from the nipple, in whom ultrasound-guided core needle biopsy of the anterior lesion yielded atypical ductal hyperplasia and stereotactic core needle biopsy of the posterior lesion yielded adenomyoepithelioma. Surgical excision of both sites revealed invasive ACC with foci measuring 24 mm and 4 mm, and after mastectomy without adjuvant therapy, the patient remained free of recurrence for 10 years. This case illustrates that ACC of the breast can be misclassified as atypical ductal hyperplasia or adenomyoepithelioma on core needle biopsy and underscores the importance of radiologic-pathologic correlation and surgical excision of high-risk or discordant lesions.

Ambient artificial intelligence (AI) scribes are increasingly being adopted to address the clinical documentation burden associated with electronic health records (EHRs), which contributes to physician burnout, after-hours work, and reduced patient-clinician interaction. These systems capture clinician-patient conversations and use speech recognition and natural language processing (NLP) to generate draft clinical notes. Newer platforms are evolving into AI clinical copilots with additional functions such as pre-charting, clinical prompting, and safety checks. This article presents a structured, evidence-informed narrative synthesis and leadership analysis of ambient AI scribe implementation in hospital settings. Using Leavitt's Diamond model of organizational change, we examine the interdependent roles of Structure, Technology, People, and Process/Task in shaping successful adoption. Early evidence suggests meaningful reductions in documentation time, increased same-day note completion, and improvements in clinician-reported workload and engagement. However, certain risks and uncertainties remain, including transcription errors, hallucinated or omitted clinical content, variable performance across specialties, accents, and care settings, unresolved medico-legal liability, privacy/data-use concerns, uneven clinician adoption, and unclear short-term financial return on investment (ROI). We argue that the successful implementation of ambient AI scribes depends less on technical capability alone and more on prudent healthcare leadership and multidisciplinary governance. It also requires robust consent and data-protection frameworks, workflow redesign, clinician training, and ongoing monitoring of quality, safety, and well-being outcomes. Our principal contribution is a structured, domain-by-domain implementation framework that translates these requirements into concrete leadership questions, recommendations, accountable owners, and metrics for hospital leaders adopting ambient AI scribes. While ambient AI scribes promise to reduce administrative burden and restore time for patient-centered care, their potential will only be realized through strategically governed adoption aligned with an organization's culture and broader health-system priorities.

INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive malignancy with poor prognosis, and (Fn) colonization further aggravates tumor progression, immunosuppression and therapeutic resistance. Conventional monotherapies are limited by insufficient tumor targeting, rapid drug clearance and failure to reverse immune suppression. Here, we fabricated cRGD-modified nanoparticles (Ag@GQDs/QUE-siP-c-L) for co-delivery of AgNPs, quercetin (QUE) and PD-L1 siRNA (siP). METHODS: The morphology, particle size, surface metal elements, drug content and QUE entrapment efficiency of Ag@GQDs/QUE-siP-c-L were obtained using particle size analysis, SEM, inductively coupled plasma-optical emission spectrometry (ICP-OES) and HPLC. We further detected cellular uptake, in vitro drug release, cytotoxicity, intracellular reactive oxygen species level, PD-L1 gene silencing efficiency and in vitro anti-Fn activity. Pharmacokinetics and tissue distribution of Ag and QUE were analyzed by ICP-OES and LC-MS/MS, and in vivo antitumor efficacy and biosafety were tested in Fn-colonized orthotopic 4T1 tumor mice. RESULTS: Ag@GQDs/QUE-siP-c-L exhibited uniform spherical morphology (195.87± 15.96 nm) with high encapsulation of QUE. cRGD modification enhanced Ag/QUE cellular uptake in 4T1 cells, with pH-responsive release accelerated under tumor acidic conditions. The nanoparticles exhibited selective tumor cytotoxicity, induced oxidative stress, downregulated PD-L1 mRNA, and exerted potent anti-Fn activity in vitro. Pharmacokinetics revealed increased AUC and reduced clearance compared with free drugs, and cRGD modification promoted tumor accumulation and retention of drugs. In vivo preliminary experiments proved the Ag@GQDs/QUE-siP-c-L formulation suppressed tumor growth with a tumor inhibition rate of 45%, and effectively modulated the tumor immune microenvironment: it increased tumor-infiltrating CD3⁺CD4⁺ T cells, reduced PD-L1⁺CD11c⁺ dendritic cells, and decreased the proportions of immunosuppressive Tregs and MDSCs. Hematoxylin-eosin staining and serum liver-kidney biochemistry confirmed no obvious systemic toxicity. CONCLUSION: Ag@GQDs/QUE-siP-c-L serves as a multimodal nanoplatform for -associated TNBC with combined in vitro antibacterial, gene silencing and in vivo antitumor immunomodulatory effects, showing great potential for future translational research.

Colorectal cancer (CRC) remains a major global health burden, with limited efficacy of conventional treatments due to tumor heterogeneity, drug resistance, and systemic toxicity. Lipid metabolism reprogramming has emerged as a hallmark of CRC progression, influencing tumor growth, metastasis, and therapy resistance. Concurrently, nanomedicine offers innovative platforms for targeted drug delivery to to inhibit tumor progression by intervening in the lipid metabolism, including modulation of lipid synthesis, uptake, storage, and cholesterol metabolism. This review provides an integrated perspective, systematically summarizing therapeutic strategies and research progress on nanodrugs targeting lipid metabolic reprogramming in CRC. We highlight nanoplatforms engineered to deliver inhibitors of key enzymes and signaling pathways, such as PI3K/AKT and Wnt/β-catenin. Representative nanoplatforms are discussed to illustrate diverse strategies for regulating lipid metabolic vulnerabilities in CRC, such as carrier-free nanoparticles, RBC membrane-coated nanocages and cholesterol-responsive nanoparticles. We also discuss the challenges in clinical translation, including tumor heterogeneity, biosafety, large-scale production, and clinical validation. Furthermore, we provide insight into translational challenges, emerging trends, and future directions for integrating lipid-targeted nanotherapies into clinical practice.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have achieved remarkable success in treating advanced cancers, yet the accompanying immune-related adverse events (irAEs) pose a major challenge to their clinical application. Growing evidence suggests an association between irAEs and improved clinical outcomes; however, the heterogeneity in this relationship warrants further exploration. CASE PRESENTATION: This article reports two cases of patients with advanced cancer who achieved long-term disease control after experiencing severe irAEs. Case one involved a patient with heavily pretreated Luminal B1 advanced breast cancer who developed Grade 3 immune-related arrhythmia and heart failure following treatment with Toripalimab combined with chemotherapy. Case two involved a patient with ROS1-fusion advanced lung adenocarcinoma who, after developing resistance to Crizotinib, received chemotherapy and Tislelizumab, leading to Grade 3 immune-related hypopituitarism, adrenal insufficiency, and cutaneous toxicity. Both patients were managed with corticosteroids with or without immunosuppressants and discontinued all antitumor therapies. Despite this, they have achieved a partial response (PR) with a duration of response (DoR) of 22 and 37 months, respectively, and both responses are ongoing at the time of this report. CONCLUSION: In this series, two patients with advanced solid tumors achieved durable tumor responses after developing severe irAEs and discontinuing treatment, suggesting that severe irAEs may herald the establishment of long-term immune memory. However, the association between irAEs and efficacy is not straightforward, as the type and severity of irAEs and the use of immunosuppressive intervention all influence the ultimate clinical benefit. In the absence of reliable predictive biomarkers, clinical decisions should not equate irAEs directly with efficacy markers; rather, the benefits and risks of immune activation should be carefully weighed.

BACKGROUND: Patients with cancer frequently experience sleep-related symptoms and physiological disturbances that may be associated with sleep-disordered breathing (SDB) and nocturnal hypoxia. Although these conditions have attracted increasing attention in oncology, the potential contribution of craniofacial restriction and upper airway dysfunction remains insufficiently recognized in routine clinical practice. OBJECTIVE: To propose a stomatological and upper airway assessment framework for the identification of anatomical factors that may contribute to sleep-disordered breathing and nocturnal hypoxia in adults with cancer. METHODS: This narrative review integrates current evidence on sleep-disordered breathing, nocturnal hypoxia, craniofacial development, and upper airway dysfunction. The proposed framework was developed from recurrent clinical observations in adults with cancer together with a narrative synthesis of the available literature, with emphasis on anatomical findings identifiable during routine stomatological examination. MAIN FINDINGS: Current evidence indicates that anatomical features such as maxillary constriction, nasal airway narrowing, altered craniofacial development, and ankyloglossia may contribute to upper airway dysfunction and nocturnal hypoxia. Despite increasing recognition of the systemic consequences of nocturnal hypoxia, these upstream anatomical factors are rarely incorporated into routine oncological assessment. Based on the available evidence, a practical clinical framework is proposed to facilitate early identification of patients who may benefit from further respiratory evaluation. CONCLUSION: Integrating stomatological and upper airway assessment into the multidisciplinary evaluation of adults with cancer may improve recognition of previously unrecognized sleep-disordered breathing and nocturnal hypoxia. This framework provides a clinically applicable approach for identifying potentially modifiable anatomical contributors to respiratory dysfunction and may support future research evaluating their relevance in supportive cancer care.

OBJECTIVES: Japan NBI Expert Team (JNET) Type 1 classification is used for optical characterization of colorectal lesions with magnifying NBI, but reported Type 1-related findings may differ between readers when assessing serrated lesions. This small-scale post hoc reader-based study explored reported feature-classification patterns associated with JNET Type 1 selection among serrated colorectal lesions and compared them between expert and non-expert endoscopists. METHODS: We analyzed de-identified data from two web-based image-interpretation studies using the same colorectal lesion image dataset. Thirteen histologically confirmed serrated lesions (11 sessile serrated lesions [SSLs] and two hyperplastic polyps [HPs]) assessed by 27 expert and 49 non-expert Japanese endoscopists were included. Simplified JNET responses were dichotomized as Type 1 versus non-Type 1. Classification and regression tree analysis was used to visualize associations between this outcome and predefined features, including Type 1-supportive findings and an anti-Type 1 composite variable. Variability was assessed using entropy. RESULTS: In the expert and non-expert core models, the root splits were anti-Type 1 findings and regular dark or white spots, respectively. These root splits were stable in leave-one-reader-out analyses, but the non-expert root split changed to anti-Type 1 findings after excluding unassessable responses. Median entropy was lower among experts than non-experts (0.229 vs. 0.954). CONCLUSIONS: This exploratory post hoc decision tree analysis suggested relatively stable expert-associated feature-classification patterns, whereas non-expert patterns were influenced by the treatment of unassessable responses. These findings reflect exploratory associations in Type 1 assignment, not cognitive decision sequences, SSL-HP differentiation, or a validated diagnostic algorithm.

Ovarian cancer remains highly lethal due to late diagnosis, frequent recurrence, and rapid development of resistance to platinum-based chemotherapy. Although rational drug combinations targeting multiple oncogenic pathways hold promise, their clinical utility is often compromised by dose-limiting toxicity and tumor heterogeneity. Antibody-drug conjugates (ADCs) offer an alternative by delivering potent agents directly to tumor cells, thereby reducing systemic toxicity. This approach could be further enhanced by the dual targeting of co-expressed tumor-specific cell surface receptor pairs to broaden tumor coverage and enable the precise delivery of synergistically active drugs. Furthermore, nanotechnology-based carriers extend these concepts by enabling the integration of multiple targeting ligands and payloads into a single drug-delivery platform. Systematic identification and validation of novel co-targeting cell surface receptors, such as G protein-coupled receptors (GPCRs), characterized by high tumor relevance and rapid internalization, may improve tumor coverage and drug uptake in therapy-resistant subpopulations. The outlined strategies are very promising to advance precise and personalized treatment strategies for ovarian cancer. However, dual-receptor approaches remain largely investigational, with limited preclinical validation, and their clinical translation is challenged by receptor heterogeneity, uncertain tumor selectivity, potential off-target effects, and inefficient delivery due to tumor-microenvironment barriers. Furthermore, manufacturing, safety, and regulatory requirements need to be addressed.

BACKGROUND AND AIMS: Cabazitaxel has demonstrated survival benefits in patients with metastatic castration-resistant prostate cancer (CRPC). However, Japanese patients are reported to experience higher rates of hematologic toxicity compared to their Caucasian counterparts. Although primary prophylaxis with pegfilgrastim is now routinely used in clinical practice, febrile neutropenia (FN) may still occur. In this study, we aimed to evaluate the real-world safety of cabazitaxel with universal pegfilgrastim prophylaxis in Japanese patients with CRPC, particularly focusing on FN during the first treatment cycle. METHODS: We retrospectively evaluated 86 patients with CRPC who received cabazitaxel at Showa Medical University-affiliated hospitals between 2015 and 2021. Cabazitaxel was administered every 3-4 weeks at doses determined by the treating physicians, generally 20-25 mg/m, with daily oral prednisolone. Pegfilgrastim was administered to all patients at least 24 h after cabazitaxel. Univariate analyses were performed to identify baseline factors associated with FN occurring during the first cycle of cabazitaxel. Exploratory logistic regression analysis was additionally performed for FN occurring during the entire treatment course. RESULTS: Among the 86 patients, FN occurred in 12 patients (14.0%) during the entire treatment course, including 8 events (9.3%) during the first cycle. In univariate analyses, the only factor significantly associated with first-cycle FN was a longer interval from CRPC diagnosis to cabazitaxel initiation (median, 1194.5 vs. 689 days,  = 0.0094). A similar tendency was observed when FN occurrence during the entire treatment course was analyzed. In exploratory logistic regression analysis for FN during the entire treatment course, the same factor showed a consistent trend toward association with FN development. CONCLUSION: Despite universal pegfilgrastim prophylaxis, approximately 10% of Japanese patients developed FN during the first cycle of cabazitaxel therapy. A longer interval from CRPC diagnosis to cabazitaxel initiation showed a consistent trend toward association with FN risk in Japanese patients across analyses. These findings provide real-world safety data and highlight the importance of careful hematologic monitoring, particularly in patients treated later in the CRPC disease course.

Familial isolated pituitary adenoma (FIPA) accounts for approximately 2%-5% of all pituitary adenomas, with inactivating variants of the aryl hydrocarbon receptor-interacting protein () gene representing the most frequent known genetic cause. Clinically, patients with variants often have young-onset macroadenomas with growth hormone hypersecretion, although disease severity and penetrance are variable. Most reported variants are point mutations, whereas large deletions are rare and potentially underdiagnosed. Accurate detection of copy-number variants requires methods such as multiplex ligation-dependent probe amplification or validated copy-number analysis of next-generation sequencing data, as Sanger sequencing alone may fail to identify these alterations. Due to the rarity of the disease, it is unknown whether large deletions in the ubiquitously expressed gene are associated with potentially more severe phenotype. Available data suggest that large deletions may occur in 8%-10% of mutation-positive pedigrees, highlighting the importance of incorporating copy-number variant detection into testing workflows. We analysed data from all published patients with large deletions ( = 25) and report here two novel large deletions (Exons 3-4 and Exons 2-6 deletions) and three additional three families, including an Albanian kindred associated with metastatic Hürthle cell thyroid carcinoma. No major differences compared with other variants were found in age at diagnosis, tumour size, hormonal profile, sex distribution or presence of other tumours. A role for variants in thyroid carcinogenesis is unlikely.

INTRODUCTION: Polycystic kidney disease (PKD) is a condition that encompasses the development of multiple benign cysts in the kidneys and other organs. Hereditary PKD can be classified as autosomal dominant polycystic kidney disease (ADPKD) or autosomal recessive polycystic disease (ARPKD). These two forms differ primarily in their age of onset and clinical presentation. ADPKD is usually diagnosed during young adulthood, whereas ARPKD presents a wide range of clinical manifestations with approximately one-third of patients presenting before the first year of life, one-third between 1 and 20 years of age, and the remaining one-third after 20 years of age. ARPKD represents the severe form, typically presenting in infancy with significant renal and hepatic involvement. Hereditary and congenital forms are known to be caused by certain genetic defects associated with dysfunction of the primary cilia in the tubular epithelium. To the best of our knowledge, no similar cases have been reported in Jordan or neighboring countries. CASE PRESENTATION: We report a case of ARPKD in one fetus of a twin pregnancy. Prenatal ultrasonography at the 20th week of gestation revealed characteristic findings of ARPKD in one fetus. The twins were delivered at 36 weeks gestation. The affected twin died shortly after birth because of severe respiratory distress. Postnatal exome sequencing (ES) on the deceased infant identified a pathogenic homozygous variant in the polycystic kidney and hepatic disease ( gene, supporting the genetic diagnosis of ARPKD. DISCUSSION: Management of ARPKD requires multidisciplinary care, emphasizing supportive therapy and monitoring for complications. Genetic counseling is pivotal, highlighting the risk of disease transmission and the role of prenatal genetic screening for at-risk families. CONCLUSIONS: Our case highlights the importance of early diagnosis, comprehensive management, and genetic counseling in ARPKD, particularly within the Jordanian population as well as neighboring demographics with high rates of consanguinity.