Log file-based patient specific quality assurance (PSQA) in scanned particle therapy relies on the consistency of spot position information recorded by the spot position monitor (SPM), but practical methods for routine independent verification of these coordinates remain limited.

This study describes a practical framework for routine verification of SPM coordinate consistency using independent scintillator-based measurements in raster-scanning carbon-ion radiotherapy.

Reference spot positions were measured at the isocenter plane using a scintillator-based detector. Corresponding SPM-recorded spot coordinates were extracted from delivery log files. The two coordinate sets were aligned using a similarity transformation accounting for translation, rotation, and isotropic scaling. Post-transformation root-mean-square (RMS) residuals were used as a practical consistency metric reflecting the agreement between SPM-reported and independently measured spot positions under routine QA conditions.

After similarity transformation, the median RMS residual across all investigated accelerator energies and irradiation ports was 1.45 mm, with an interquartile range of 1.36-1.63 mm. No statistically significant difference was detected across accelerator energies, whereas a significant difference was observed among irradiation ports.

The proposed framework provides a practical approach for routine verification of SPM coordinate consistency and for establishing facility-specific baselines through longitudinal monitoring. The RMS residual should not be interpreted as the intrinsic positional error of the SPM alone, but to provide a framework for establishing a facility-specific baseline for monitoring the agreement between SPM-reported and independently measured spot coordinates under routine QA conditions.

Liver metastasis represents one of the frequent drivers for cancer-related mortality in lung adenocarcinoma. For advanced lung adenocarcinoma harboring wild-type oncogene drivers, chemotherapies in combination with immune checkpoint inhibitors (ICIs) and/or bevacizumab (named IC, BC, and IBC, respectively) are alternative first-line schemes as recommended by canonical treatment guidelines. However, due to the immunosuppressive tumor microenvironment in the liver, patients with liver metastases are less effective to ICIs. For this subpopulation, the optimal regimen is still undetermined.

In this retrospective multicenter cohort study, treatment-naïve lung adenocarcinoma patients with wild-type oncogene drivers and liver metastases were enrolled from 4 cancer centers between January 2018 and December 2023. All these patients received BC, IC, or IBC as the first-line therapies. Propensity Score Matching (PSM) was applied to balance baseline covariates. Kaplan-Meier survival analysis, log-rank tests, and Cox proportional-hazards regression were used to compare PFS and OS among groups.

A total of 191 Patients were enrolled, in which 70 (36.6%) received IC treatment, 70 (36.6%) received BC and 51 (26.7%) received IBC treatment. After PSM, 135 eligible patients were selected, including 45 Patients in each group. IBC group showed a slightly higher ORR (44.4%) and significantly higher DCR (95.6%, p = 0.013) compared with BC (ORR = 37.2%, DCR = 81.4%) and IC (ORR = 38.5%, DCR = 71.8%) groups, as evaluated by the primary lung lesions. When liver metastases were used as target lesions, similar response was observed. The median progression-free survival (mPFS) in patients receiving IBC (8.48 months, 95% CI: 5.98-16.10 months) was significantly longer than those receiving BC (5.09 months, 95% CI: 3.55-7.46 months) and IC (4.86 months, 95% CI: 3.06-7.82 months) (IBC vs. BC: HR = 0.477, 95% CI: 0.295-0.772, p = 0.002; IBC vs. IC: HR = 0.479, 95% CI: 0.292-0.784, p = 0.003). IBC also showed a numerically longer OS than IC (18.99 months vs. 12.52 months; HR = 0.692, 95% CI: 0.429-1.114, p = 0.128), although this difference did not reach statistical significance. Subgroup analyses, conducted as pre-specified exploratory analyses, showed that patients with male gender, smoking history, brain metastasis, polymetastases and low PD-L1 expression (< 50%) displayed superior PFS when treated with IBC compared with their counterparts. Besides, IBC showed comparable adverse events relative to IC and BC treatments.

IBC treatment showed superior efficacy in oncogene wild-type lung adenocarcinoma patients with liver metastases, especially in those with male gender, smoking history, brain metastasis, polymetastases, and low PD-L1 expression.

Proton pump inhibitors (PPIs) raise stomach pH, leading to reduced bioavailability of many tyrosine kinase inhibitors (TKIs), thereby affecting treatment outcomes. To what extent this interaction occurs in clinical practice remains underexplored.

To determine the frequency of clinically relevant interactions between TKIs and PPIs in clinical practice and the duration of concomitant prescription.

A retrospective observational study was performed using the IADB.nl prescription database. Clinically relevant drug-drug interactions between TKIs and PPIs were assessed using four drug compendia (i.e., KNMP Kennisbank, Health Base, Lexidrug and Merative Micromedex). Patients who were prescribed a TKI and PPI with a clinically relevant DDI concomitantly, between 1 January 2013 and 31 December 2024, were included. Concomitant prescription was defined as ≥ 7 days of simultaneous prescription.

In total, 60 TKIs were registered in the Netherlands; 19 TKIs had clinically relevant interactions reported by at least one compendium. Overall, 393 of 1759 (22.3%) TKI users had a clinically relevant interaction. The median duration of concomitant prescription was 43 days (IQR = 81), with 91.1% of episodes lasting at least 30 days.

PPIs and TKIs are frequently prescribed concomitantly in clinical practice. Prescribers should be more cautious when co-prescribing PPIs with TKIs and adapt the dosing regimens when appropriate.

Xeroderma pigmentosum (XP) is an inherited photoaging syndrome caused by mutations in genes involved in the nucleotide excision repair (NER) pathway. XP patients exhibit hypersensitivity to ultraviolet (UV) radiation, leading to accelerated skin aging and requiring lifelong sun avoidance. In this study, we aimed to investigate UV-induced cellular senescence in XP melanocytes and explore potential senotherapeutic strategies.

Melanocytes differentiated from iPSCs derived from an XP-A patient and a healthy individual, respectively, were used to induce senescence. Senescence was assessed by SA-β-gal and γH2AX staining. The drug screening tested a panel of 12 senolytic agents and 15 senomorphic agents for their ability to target senescent XP-iMCs. The effects of these agents were evaluated through cell viability assays and SPiDER-βGal staining followed by flow cytometry. RNA sequencing was performed to analyze transcriptional changes induced by senomorphic treatments.

We demonstrate that UV-induced DNA damage triggers cellular senescence and up-regulates senescence-associated secretory phenotype (SASP) genes in melanocytes derived from an XP patient. The drug screening identified JAK inhibitors and curcuminoids as promising senomorphic agents. In addition, two classes of senolytic agents, BCL-2-like protein inhibitors and HSP90 inhibitors, effectively eliminate senescent melanocytes. Further analysis demonstrates that senomorphic treatment effectively counteracts senescence and reduces SASP gene expression in XP-derived melanocytes. Moreover, genes in senescence-related pathways, including the cytokine-cytokine receptor interaction, JAK/STAT, and PI3K/AKT pathways, which are activated in senescent cells, are down-regulated by senomorphic treatment.

This study highlights a potential senotherapeutic strategy for XP, which may help alleviate photoaging symptoms in XP patients.

Ovarian steroid cell tumor (SCT) is a rare ovarian neoplasm with uncertain malignant potential. This study aimed to evaluate the oncologic and reproductive outcomes of patients with ovarian SCTs.

We retrospectively reviewed patients with ovarian SCTs who underwent surgery at Peking Union Medical College Hospital between January 2008 and August 2025. Patients were classified into fertility-sparing surgery (FSS) and non-FSS groups according to surgical approach. Clinical features, oncologic outcomes, hormonal recovery, and reproductive outcomes were analyzed.

Thirty patients were included, with 19 in the FSS group and 11 in the non-FSS group. The median age of patients was 27 (range: 4-42) in the FSS group and 55 (range: 25-80) in the non-FSS group (P < 0.001). In the FSS group, 63.2% (12/19) of patients had FIGO stage IA disease, 26.3% (5/19) had stage IC1 disease, and 10.5% (2/19) had stage II disease, whereas all patients in the non-FSS group had FIGO stage IA disease (P = 0.029). Elevated serum testosterone levels with virilizing manifestations were observed in all FSS patients and in 45.5% of non-FSS patients. No recurrence was observed among patients with FIGO stage IA disease in either group. Recurrences occurred in a patient with stage IC who underwent ovarian cystectomy and in two patients with stage II in the FSS group, one of whom died of disease. At the last follow-up, only one patient clearly reported an active desire for childbearing and subsequently achieved a spontaneous twin pregnancy with live birth. Median follow-up was 61 months (range: 6-184) in the FSS group and 67 months (range: 4-160) in the non-FSS group.

Ovarian SCTs confined to FIGO stage IA were associated with favorable oncologic outcomes in our cohort, whereas recurrence occurred in patients with stage IC or II disease. For patients with stage IA disease desiring fertility preservation, unilateral salpingo-oophorectomy (USO) may be considered. Fertility preservation in stage IC or II disease should be individualized with caution. Long-term follow-up and multi-institutional studies are needed to better define both oncologic and reproductive outcomes.

Mucinous adenocarcinoma of the colon is defined by extracellular mucin occupying at least 50% of the tumour. Although it is often regarded as a distinct histological subtype, its clinicopathological profile remains variable across published series. We compared mucinous and classic adenocarcinoma in a colon-only surgical cohort.

We retrospectively reviewed patients who underwent oncological resection for colon adenocarcinoma between October 2021 and March 2026. Rectal tumours, neoadjuvant-treated cases and signet ring cell carcinoma were excluded. Clinicopathological variables were compared using Mann-Whitney U, Pearson chi-square or Fisher exact tests. Multivariable analyses were revised as parsimonious logistic regression models, with model size and event counts reported.

The final cohort included 155 colon cancers: 29 mucinous and 126 classic adenocarcinomas. Mucinous tumours were more often right-sided (75.9% vs. 44.4%; p = 0.002) and more frequently poorly differentiated (24.1% vs. 4.8%; p = 0.003). Advanced pT stage was common in both groups (86.2% vs. 82.5%; p = 0.786). Nodal metastasis was numerically less frequent in mucinous adenocarcinoma (31.0% vs. 50.8%; p = 0.055), while lymphovascular invasion was significantly less common (10.3% vs. 32.5%; p = 0.017). Deficient mismatch repair was recorded in 13.8% of mucinous tumours and 8.7% of classic adenocarcinomas (p = 0.484). In parsimonious adjusted models, mucinous histology was not independently associated with advanced pT stage (adjusted OR 1.51, 95% CI 0.46-4.92; p = 0.496) or nodal metastasis (adjusted OR 0.48, 95% CI 0.19-1.19; p = 0.113).

In this colon-only cohort, mucinous adenocarcinoma was associated with right-sided location and poor differentiation, but not with independently higher local invasion or nodal spread. These findings support a cautious, clinicopathology-based interpretation of mucinous histology and should not be extrapolated to prognosis without molecular and survival data.

The purpose of this study is to characterize patient-reported taste disturbances, recalled symptom course, nutritional changes, and quality of life in patients with relapsed/refractory multiple myeloma treated with talquetamab. This single-center cross-sectional study combined taste-strip testing with a study-specific questionnaire, EORTC QLQ-C30, and PHQ-4 in 32 patients. Analyses used recorded aggregate correct-identification counts without a normative hypogeusia classification. Symptom timing and changes since treatment initiation were recalled at one assessment. All patients reported taste disturbances during therapy. The median identification count was 2.5 (interquartile range 0.75-7.25); eight patients had no correct identifications. Twenty-three (71.9%) described onset within 14 days. Current appetite reduction was reported by 20 patients (62.5%), whose mean identification count was lower than that of the other 12 patients (2.45 versus 7.83; mean difference - 5.38, 95% confidence interval - 8.20 to - 2.57; p = 0.0006). Sixteen patients (50.0%) reported directional weight loss, with a median loss of 4.5 kg. Ten (31.3%) had considered stopping talquetamab; seven explicitly cited taste disturbance. Mean global health status was 50.5/100 and correlated with identification count (r = 0.406; p = 0.021). Taste disturbances co-occurred with substantial nutritional concerns. Lower taste-identification counts were associated with current appetite reduction and lower global health status. The findings support attention to taste-related burden but do not establish causality, sustained recovery, or effects on adherence. Prospective evaluations of supportive care are needed.

In locally advanced gastric cancer, a substantial number of patients relapse with liver metastasis months after an apparently curative operation, and standard tumor staging offers little warning of who is at risk. Here, we develop the Radiopathomics-Clinical Stratification Assessment (RCSA), an interpretable model that integrates three complementary sources of information: radiomic features from preoperative computed tomography, pathomic features from routine hematoxylin and eosin tumor slides, and conventional clinical features. Trained on patients from one hospital and then tested on separate internal, external, public, and prospective trial groups (NCT02555358), RCSA consistently separates high- and low-risk patients, with area under the curves between 0.862 and 0.909. Tumors it labels low-risk carry a notably more active immune environment, indicating that these patients are the ones most likely to gain from added immunotherapy. RCSA therefore turns existing hospital data into individualized guidance for postoperative follow-up and treatment.

RATIONALE-306 previously demonstrated improved overall survival (OS) in participants treated with tislelizumab plus chemotherapy versus those receiving placebo plus chemotherapy as first-line treatment for advanced/metastatic esophageal squamous cell carcinoma, with a minimum follow-up of approximately 15 months. Exploratory long-term efficacy, safety, and quality of life (QoL) analyses after 36.0 months' minimum follow-up are reported here. Patients (649) were randomized 1:1 to tislelizumab 200 mg or placebo with investigator-chosen chemotherapy. Tislelizumab plus chemotherapy improves OS versus placebo plus chemotherapy in all patients (17.2 versus 10.6 months; hazard ratio, 0.70; 95% confidence interval, 0.59-0.80). At 3 years, 15.0% of patients treated with tislelizumab plus chemotherapy had not progressed versus 2.9% of those receiving placebo plus chemotherapy. No new safety signals have been identified. Median time to deterioration of physical functioning-a key QoL domain-has not been reached with tislelizumab plus chemotherapy versus 18.8 months with placebo plus chemotherapy. With longer follow-up, tislelizumab plus chemotherapy demonstrates long-lasting efficacy, tolerable safety, and favorable patient-reported outcomes, making it a suitable option for this patient population. ClinicalTrials.gov: NCT03783442 .

With the rise of spatially resolved transcriptomics biotechnologies, performing spatially-aware analysis of the resulting data is crucial to maximise advances in biological understanding. Dimensionality reduction is a first step in most analyses of spatial transcriptomics data, and common approaches that preserve total variation of gene expression features do not usually preserve biologically meaningful spatial variation. To this end, we develop weighted sliced inverse regression (wSIR), a sufficient dimension reduction technique that aims to retain the predictive power of the spatial coordinates. wSIR is applicable to multiple distinct spatial transcriptomic datasets and is highly scalable, with over 100, 000 cells processed in under two minutes on a standard laptop. The feature loadings are interpretable, and new non-spatial data can be projected into wSIR's low-dimensional space for downstream analyses. We examine wSIR's performance and demonstrate its biological relevance through two case studies in human breast cancer and mouse early embryonic development.