This study aimed to develop a patient-centered and partner-centered core outcome set (COS) reflecting the health-related quality of life (HRQoL) outcomes most important to patients with vulvar cancer following surgical treatment and their partners. Identifying these outcomes enables healthcare professionals to better support patients' HRQoL during and after treatment.

A mixed-methods study conducted in the Netherlands from December 2021 to March 2024 among patients with vulvar cancer, their partners, and healthcare professionals involved in their care. The study followed a three-step approach: (1) a literature review to identify HRQoL concepts and existing questionnaires; (2) interviews with patients, partners, and healthcare professionals to extract important outcomes; and (3) an online Delphi study, followed by an online consensus meeting, to prioritize outcomes. The primary outcomes were the development of patient-centered and partner-centered COS and the identification of validated questionnaires for HRQoL assessment.

The patient-centered COS comprised 45 outcomes in the domains of physiological functioning, including physical symptoms, as well as physical, sexual, and emotional functioning. The COS also included topics that are less often included in studies, i.e., wound healing, body image, and fear of recurrence. The partner-centered COS included six outcomes only focusing on information provision, not on their own HRQoL. Recommended patient HRQoL questionnaires were (scales from) EORTC QLQ-C30/VU34/SH22/INFO25 and WOUND-Q.

This is the first patient-centered COS for vulvar cancer, enabling targeted HRQoL assessments and improved daily clinical care. The provision of information was the only aspect deemed important as an outcome for partners.

Multiple population pharmacokinetic (PopPK) models have been developed across diverse populations and disease groups for high-dose methotrexate (HDMTX), and published external evaluations of PopPK models have demonstrated limited transferability across populations. This study aims to develop a PopPK model describing HDMTX pharmacokinetics in Malaysian adults with hematological malignancies via routine clinical data.

Methotrexate (MTX) plasma concentrations at 48, 72, and 96 h were retrospectively collected from 91 HDMTX administrations with a total of 206 concentrations. Concentrations below the lower limit of quantification (BLQ) were handled using M3. Potential covariates evaluated included demographic factors (age, sex, body surface area), renal function, liver function parameters, hematocrit and treatment-related factors (protocol and infusion duration). Renal function was explored via the estimated glomerular filtration rate (eGFR), BSA-adjusted eGFR (GFR), and creatinine clearance derived from the Cockcroft-Gault equation, to assess their relative influence on clearance. Forward inclusion followed by backwards elimination was used for covariate selection. Model adequacy was assessed using goodness-of-fit plots and visual predictive check (VPC).

A two-compartment model with literature-informed distribution parameters, first-order elimination and combined residual error best described the current data. Limited information during the distribution phase was mitigated by fixing V1, V2, and Q to the literature-derived values. Clearance (CL), normalized to the median covariate values was parameterized as: CL (L/h) = 11.13 × (Alb/39)^0.7. Albumin was a significant predictor of CL (ΔOFV = -41.81 from 119.92 in base model).

This model characterizes HDMTX pharmacokinetics in Malaysian adults with hematological malignancies, with albumin identified as a significant covariate on clearance. Simulation findings suggest that albumin may support risk stratification for delayed MTX elimination across different dosing scenarios.

Mercaptopurine (6-MP) is a cornerstone drug for acute lymphoblastic leukemia (ALL) maintenance therapy. As a prodrug and purine analog, 6-MP is converted into the active cytotoxic product through a series of metabolic processes in the body. Its cytotoxic effects are mediated by the overactivation of deoxyribonucleic acid (DNA) mismatch repair mechanisms. The metabolism of 6-MP is influenced by multiple enzymes, and genetic polymorphisms encoding these enzymes affect drug tolerance and adverse reactions. Owing to significant individual variability, therapeutic drug monitoring (TDM) during 6-MP therapy has gained increasing attention, although no consensus has yet been established. Therefore, optimizing 6-MP maintenance regimens to mitigate adverse reactions and increase efficacy during this phase is critically important. Currently viable strategies include thiopurine enhanced ALL therapy (TEAM) and combination therapy with allopurinol. Finally, the issue of 6-MP resistance is attracting attention. Identifying methods for early detection of acquired resistance and developing corresponding strategies is important for improving the prognosis of ALL patients.

Robotic-assisted surgery (RAS) for rectal cancer is increasingly adopted. However, a recent systematic review highlighted a significant gap in the literature regarding quality of life (QOL) after different total mesorectal excision (TME) techniques, with open TME being particularly underrepresented. This study aimed to compare QOL and anorectal function between robotic-assisted and open low anterior rectal resection with TME.

Patients who underwent low anterior rectal resection with TME and primary anastomosis between 2006 and 2021 at a single tertiary centre were identified. Propensity score matching was performed based on sex, age, BMI, UICC stage and tumour height. After excluding patients without QOL follow-up or with a persistent diverting stoma, 40 patients per group were available. QOL was assessed using the EORTC QLQ-C30, QLQ-CR29, and LARS score.

In the matched cohort, baseline characteristics were well balanced except for tumour height (p = .002), with more lower-third tumours in the open group. No significant differences were observed in any EORTC QLQ-C30 domain, including global health status (66.5 vs. 71.7, p = .197). QLQ-CR29 showed comparable outcomes for most domains; however, sexual interest was significantly lower in the RAS group for women (88.1 vs. 55.6, p = .008). LARS scores were similar between groups (24.4 vs. 25.6, p = .765). Perioperative outcomes including morbidity (10.0% vs. 22.5%, p = .130) and anastomotic leakage (2.5% vs. 5.0%, p = .526) did not differ significantly.

Robotic-assisted and open low anterior rectal resection with TME resulted in comparable QOL and anorectal function across all assessed domains. Notably, approximately one third of patients in both groups reported major LARS, underscoring the persistent functional burden irrespective of surgical approach. By providing direct comparative data on open TME - an approach underrepresented in the literature - these findings contribute to closing an important evidence gap.

Special treatment of very important persons (VIPs) is widely believed to cause deviation from standard care and worse outcomes, but has rarely been tested objectively, especially in surgery. We examined whether VIP status is associated with worse outcomes after robot-assisted radical prostatectomy and the burden surgeons report when operating on such patients.

In a single-centre retrospective study, 75 patients flagged as VIP among 571 men undergoing robot-assisted radical prostatectomy for non-metastatic prostate cancer were matched 1:4 to 300 controls by a propensity score from eight covariates, with exact matching on surgeon (analytic cohort, 375). Perioperative outcomes, complications, and readmission were compared, and six surgeons completed an exploratory eight-item burden survey.

After matching, covariates were well balanced (all standardised mean differences below 0.10 except operative year, 0.130). Surgical and complication outcomes showed no difference (complications: risk difference +8.0 points, 95% confidence interval -2.0 to +18.0). The exception was inpatient antibiotic days, longer in VIPs by 0.87 days (95% confidence interval +0.17 to +1.57), though concentrated in one surgeon and non-significant once that surgeon was excluded (interaction p < 0.001). Surgeons reported higher cognitive strain and a greater defensive-prescribing impulse, yet their reported intent and actual prescribing correlated only weakly and non-significantly.

VIP status was not associated with worse objective outcomes, but a few surgeons prolonged antibiotics defensively without clear benefit, while their reported burden stayed high, dissociating perception from outcome. Maintaining standard, protocol-based care and antimicrobial stewardship for every patient is the safe and equitable response; the small sample limits precision.

Background Previous studies on imaging of hepatocellular carcinoma (HCC) have shown inconsistency in the growth of tumor vascularity and gross morphologic features. Contrast-enhanced US (CEUS) is one of the few methods that can depict both features simultaneously, making it valuable for assessing this inconsistency and its potential clinical influence. Purpose To evaluate and establish a new CEUS feature representing inconsistency between vascularity and gross morphologic features (perfusion beyond margin [PBM]) and analyze its underlying biologic mechanisms and prognostic influence. Materials and Methods This multicenter retrospective study included patients with HCC from January 2015 to August 2023. Three radiologists (5-8 years of experience) measured tumor diameter using gray-scale US and CEUS. Mathematic, prognostic, and bioinformatics analyses were used to quantify the PBM diagnostic standard. Prognostic analysis included recurrence-free survival after laparoscopic hepatectomy and local tumor progression-free survival after thermal ablation. Bioinformatics analysis included pathologic and immunohistochemical evaluation and RNA sequencing. Results This study included 1076 patients (mean age ± SD, 60 years ± 10.5; 854 men, 1166 HCCs). PBM was defined as the tumor diameter on arterial phase exceeding that at gray-scale US by 5 mm. PBM was associated with worse recurrence-free survival (hazard ratio [HR], 1.76 [95% CI: 1.05, 2.94]; P = .03); worse local tumor progression-free survival (HR, 2.40 [95% CI: 1.84, 3.13]; P < .001); and higher rates of microvascular invasion (52.2% [12 of 23] vs 25.0% [29 of 116]; P = .02), cytokeratin-7 positivity (26.2% [11 of 42] vs 11.3% [14 of 124]; P = .04), and cytokeratin-19 positivity (26.9% [seven of 26] vs 8.8% [13 of 148]; P = .02) compared with the non-PBM group. PBM occurrence was related to upregulation of genes for angiogenesis (VEGA, PIGF), epithelial-mesenchymal transition (TGFB1, MMP2), and immunosuppressive tumor microenvironment (CD163). PBM was more common in patients with cirrhosis (26.8% [236 of 880]; P = .04; odds ratio, 1.41), recurrent tumors (28.4% [161 of 567]; P = .02; odds ratio, 1.38), and tumors greater than 3 cm (30.8% [92 of 298]; P = .01; odds ratio, 1.46). Conclusion Perfusion beyond margin, a new imaging feature, was identified through contrast-enhanced US in patients with hepatocellular carcinoma; it was associated with greater invasive potential and poorer prognosis. © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Shafaat and Reis in this issue.

To compare the efficacy of an estriol-lactobacilli combination vaginal tablet (E3/L) and polycarbophil-based vaginal moisturizer (PBVM) in women with post-radiation vaginitis following cervical cancer treatment.

This open-label, randomized controlled trial recruited 34 women with Stages I-III cervical cancer who had completed pelvic radiotherapy and developed vaginal toxicity symptoms. Participants were randomized 1:1 to E3/L (Gynoflor) or PBVM (Regelle) for 4 weeks. The primary outcome was change in vaginal maturation value (VMV). Secondary outcomes included changes in vaginal pH, vaginal toxicity symptom scores, and Female Sexual Function Index (FSFI) scores.

The median improvement in VMV was significantly greater with E3/L than with PBVM (19.65 [IQR: 0-39.5] vs. 2.08 [IQR: 0-20.1] points; p = 0.035; 95% CI: 10.22-32.59). Vaginal dryness and inflammation improved significantly in the E3/L group. Changes in vaginal pH, dyspareunia, and vaginal pain were similar between groups. Although the FSFI change was greater with E3/L (median +6 vs. +2; p = 0.01), absolute FSFI scores at Week 4 were similar, and clinical significance is uncertain. Both treatments were well tolerated.

In women with cervical cancer and radiation-induced vaginitis, E3/L showed greater short-term improvements in vaginal epithelial maturation, dryness, and inflammation than PBVM over 4 weeks. These findings are exploratory given the modest sample size, open-label design, and short follow-up; larger double-blind randomized trials with extended follow-up are needed to confirm these results.

Thai Clinical Trials Registry: TCTR2024051001.

Leptomeningeal disease (LMD) is one of the most devastating complications of advanced non-small cell lung cancer (NSCLC), historically associated with profound neurologic morbidity and poor survival. Advances in cerebrospinal fluid (CSF)-based diagnostics, improved molecular characterization, and the development of central nervous system (CNS)-penetrant targeted therapies have begun to reshape both disease assessment and treatment expectations, particularly in oncogene-driven NSCLC. Available data suggest that outcomes in LMD are highly heterogeneous and are influenced by molecular subtype, performance status, systemic disease control, and access to effective CNS-active therapies. In selected patients, especially those with epidermal growth factor receptor- or anaplastic lymphoma kinase-altered disease, contemporary targeted agents have demonstrated meaningful leptomeningeal and intracranial activity, supporting more durable and compartment-specific disease control. At the same time, diagnosis still relies on imperfect but complementary modalities, including magnetic resonance imaging and CSF cytology, whereas emerging liquid biopsy approaches may improve detection and longitudinal monitoring. Treatment failure is further shaped by the pharmacokinetic constraints of the leptomeningeal compartment, where limited drug penetration contributes to therapeutic resistance. This review highlights the evolving biology, diagnosis, prognostic determinants, and therapeutic landscape of NSCLC-associated LMD, while emphasizing persistent limitations in diagnostic standardization, response assessment, and clinical trial design. It also underscores the need for leptomeningeal-specific end points, longitudinal CSF-based biomarker integration, and more inclusive trial strategies to improve evidence generation and patient outcomes.

Pancreatic ductal adenocarcinoma (PDAC) remains among the most lethal malignancies, and activating KRAS mutations occur in more than 90% of tumors. Direct RAS targeting has moved from proof of concept to randomized clinical benefit: in previously treated metastatic PDAC, daraxonrasib improved median overall survival, progression-free survival, and objective response rate versus chemotherapy. Mutation-selective G12C and G12D inhibitors, targeted degraders, and first-line RAS(ON) combinations further broaden the landscape. Comprehensive germline and somatic profiling remains essential even with the availability of multi-selective KRAS inhibitors. KRAS alleles differ biologically, drug activity against individual alleles is not yet fully characterized, and eligibility for clinical trials often depends on the specific genotype. In addition, KRAS wild-type tumors may harbor actionable alterations, including gene fusions, amplifications, or mismatch-repair deficiency. This review synthesizes RAS biology, molecular-testing implications, clinical efficacy and toxicity data, and ongoing phase 2 and phase 3 trials. Priority questions include optimal sequencing, management of rash and mucositis, resistance, biomarker development, and integration into first-line and curative-intent therapy.

Intracranial solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms, and cases of tumor bleeding are rarely seen. While radiographically similar to meningioma, SFTs exhibit a more aggressive clinical course. The mainstay of treatment is surgical resection followed by adjuvant radiotherapy. We present the first case of a hemorrhagic SFT located at the cerebellopontine (CP) angle, which was successfully treated with multimodal therapy. A 31-year-old man presented with a headache and altered consciousness. Neuroimaging revealed a large dural-based tumor at the left CP angle with subdural hematoma (SDH). The patient underwent preoperative endovascular embolization and near-total surgical resection. Further histopathological analysis confirmed the diagnosis of intracranial SFT. The patient recovered favorably and underwent adjuvant gamma-knife stereotactic radiosurgery (SRS) for the residual tumor. To the best of our knowledge, this is the first reported case of a hemorrhagic SFT treated with a combination of preoperative endovascular embolization and adjuvant SRS. This case illustrates that tailored multimodal treatment is both effective and safe for managing hemorrhagic intracranial SFTs.