Radiotherapy treatment plan comparisons often utilize structure doses, tumor control probabilities (TCPs), and normal tissue complication probabilities (NTCPs), but such metrics do not reflect the duration for which a patient suffers from a developed toxicity. Markov models allowing for the simulation of the patient's entire lifetime post-treatment and the determination of quality-adjusted life expectancy (QALE) have been developed but generally disregard important considerations such as additional treatments received and second primary malignancies (SPMs). Clinical validation also largely remains outstanding.

This study aims to expand and clinically validate a Markov model focusing on head-and-neck cancer patients.

A Markov model considering tumor control, healthy tissue toxicities, distant metastases, radiation-associated secondary cancer, and death from various causes was expanded to further include additional treatments received, SPMs, and the patient's smoking history. For each of 148 head-and-neck cancer patients, 437,000 simulations of the patient's entire lifetime post-treatment were performed and compared to the patient's clinically-documented outcomes (wherever available).

94.4% of simulations exhibited locoregional control, compared to 89.9% of patients in clinical reality. Simulated death with locoregional failure was 4.9%, compared to 5.4% in real life. Patients developed and died with distant metastases in 8.0% of simulations, while 10.8% of patients developed distant metastases in real life and 5.7% of patients passed away with distant disease. The simulated second primary cancer rate was 13.5%. Patients exhibited at least one healthy tissue toxicity in 43.8% of simulations, and simulated life expectancy and QALE were 76.5 ± 11.6 years and 74.3 ± 11.0 quality-adjusted life years (QALYs), respectively.

Agreement between simulation results and available clinically-documented outcomes was generally excellent, enabling the evaluation of prospective clinical outcomes and comparisons between different patient populations along with variable treatment combinations.

Clinical trial enrollment is essential to advancing cancer care, yet participation among patients with advanced cancer remains low. While patient-level barriers are frequently cited, the role of health care delivery factors-specifically physician- and practice-level variation-has been poorly quantified.

To quantify variation in clinical trial participation and identify associated delivery system factors among patients with advanced cancer.

This cohort study included adults with advanced or metastatic cancers diagnosed and treated between January 1, 2011, and December 31, 2024, by 1664 physicians across 107 trial-available oncology practices across the US. Data were obtained from the Flatiron Health Research Database. Analyses were conducted between January and April 2025.

Patient-level (eg, demographic characteristics, cancer type, and performance status), physician-level (eg, patient volume, subspecialization, and prior trial enrollment activity), and practice-level (eg, size, research engagement, and patient composition) factors.

The primary outcome was clinical trial participation, defined as receipt of a clinical study drug. Mixed-effects logistic regression models were used to decompose the proportion of variation attributable to patient-, physician-, and practice-level factors. Multivariable logistic regression was used to identify characteristics associated with trial participation.

Among the 205 743 patients with advanced or metastatic cancer (mean [SD] age at advanced cancer diagnosis, 67.5 [11.3]; 107 370 males [52.2%]), 10 785 (5.2%) participated in a clinical trial over the study period, increasing from 235 of 5964 (3.9%) in 2011 to 638 of 9336 (6.8%) in 2024. Participation remained highly concentrated: of 1664 physicians, 389 (23.4%) accounted for 9018 (83.6%) of all enrollments (10 785), while 21 of 107 practices (19.6%) accounted for 8686 (80.5%) of all enrolled patients. Additionally, 494 of 1664 physicians (29.7%) enrolled no patients. Physician-level (12.3%) and practice-level (15.1%) factors explained a greater share of variation in trial participation than observable patient-level characteristics (11.4%), with physician- and practice-level contributions increasing over time. Physician's subspecialization (treated 1-2 cancer groups: odds ratio [OR], 4.11 [95% CI, 2.53-6.68], P = .002; treated 3-4 cancer groups: OR, 2.38 [95% CI, 1.37-4.14], P < .001), physician's prior trial enrollment activity (enrolled patients in the 2 previous years: OR, 1.58; 95% CI, 1.43-1.76; P < .001), and practice's research engagement (OR, 2.68; 95% CI, 2.12-3.39; P < .001) were associated with higher odds of trial participation.

In this cohort study of patients with advanced cancer, clinical trial participation increased moderately but remained low over the study period, with physician- and practice-level factors consistently accounting for a substantial share of participation variation. Improving trial accrual requires interventions targeting structural factors in enrollment, including research infrastructure and physician engagement.

The Promoting Informed Decisions About Colorectal Cancer Screening in Older Adults (PRIMED) cluster randomized trial found that 2-hour online training combined with a pre-visit reminder for primary care physicians (PCPs) increased shared decision making (SDM) among patients aged 76-85 years who were due for colorectal cancer screening (CRC) screening discussions. However, the best way to translate findings from the clinical trial setting into routine primary care remains unclear.

To explore PCPs' experiences with the PRIMED SDM training and reminders, and to identify barriers, facilitators, and recommendations for implementation in routine primary care.

A qualitative study using semi-structured interviews was conducted. 59 PCPs from 35 primary care practices affiliated with five hospitals in Massachusetts and Maine who participated in the PRIMED trial were invited to be interviewed. Interviews were conducted between April and July 2021, transcribed verbatim, and analyzed by two independent researchers using a Framework Analysis-informed approach.

Of 59 PCPs, 43 participated. Themes included: (i) Training and Reminders Supported SDM; (ii) Real-World Constraints Challenged SDM Implementation, but PCPs Made Efforts to Adapt despite challenges such as time pressures, competing priorities, and the COVID-19 pandemic; and (iii) Scaling and Sustaining SDM Requires a System-Level Approach, such as automated reminders, patient decision aids, concise training, and interprofessional SDM.

Overall, PCPs perceived the SDM training and reminders as supporting a more nuanced and individualized approach to CRC screening conversations with older adults. To enable broader scale-up in primary care, these interventions should minimize burden on PCPs by streamlining integration into existing workflows.

Phosphaturic mesenchymal tumors (PMTs) are exceptionally rare neoplasms that secrete fibroblast growth factor 23 (FGF23), leading to tumor-induced osteomalacia (TIO). Owing to their nonspecific clinical manifestations and deceptively bland morphology, diagnosis is frequently delayed unless there is a high index of clinical suspicion or recognition of characteristic histopathological features. While PMTs predominantly arise in the appendicular skeleton, involvement of the sinonasal tract is uncommon, and pediatric sinonasal PMTs have not been reported previously. Although most PMTs follow a benign course, a subset demonstrates local recurrence, and predictors of recurrence remain poorly defined.

All cases of sinonasal PMTs diagnosed at our institution over a 10-year period were retrospectively reviewed. Clinical, radiological, histopathological, immunohistochemical, and molecular findings were analyzed. Immunohistochemistry was performed for SATB2, ERG, SMA, CD56, desmin, SSTR2, SSTR5, FGFR1, and Ki-67. Fluorescence in situ hybridization (FISH) was performed using FGFR1 dual-color break-apart and CDKN2A/CEP9 dual-color locus-specific probes.

Seven sinonasal PMTs were identified, including two pediatric cases (both 10-year-old females) and five adult cases (age range: 32-68 years; overall range: 10-68 years). Patients presented with non-specific symptoms, most commonly related to tumor-induced osteomalacia, while a minority presented with local sinonasal complaints. Histologically, all tumors were unencapsulated and composed of ovoid cells embedded within a characteristic pale eosinophilic stroma with prominent, often dilated vasculature. Adipose tissue was present in 6/7 (85.7%) cases, osteoclast-like giant cells and hemosiderin-laden macrophages in 4/7 (57.1%) each, whereas grungy calcification, osteoid-like matrix, and aneurysmal bone cyst-like areas were infrequent. Tumors showed diffuse expression of SATB2, ERG, SMA, CD56, and SSTR2, while FGFR1 immunohistochemistry lacked specificity. FGFR1 gene rearrangement was identified by FISH in two cases. Notably, both pediatric tumors demonstrated CDKN2A homozygous deletion and developed local recurrence, whereas none of the adult tumors showed CDKN2A loss or recurred.

Sinonasal PMTs are rare neoplasms that pose significant diagnostic challenges because of their rarity and morphological overlap with other mesenchymal tumors. Recognition of their characteristic histological features, supported by an appropriate immunohistochemical panel and FGFR1 FISH, facilitates accurate diagnosis. This study represents the first report of pediatric sinonasal PMTs and identifies CDKN2A homozygous deletion as a potential marker of recurrent behavior, warranting further investigation in larger cohorts.

Spinal ependymomas are rare tumors of the central nervous system characterized by distinct anatomical, histological, and molecular subtypes. This review aims to synthesize current evidence regarding the presentation, diagnosis, surgical management, adjuvant therapy, and outcomes of spinal ependymomas, with a focus on the pediatric population.

We conducted a narrative review of contemporary literature, consensus recommendations, and relevant treatment-related molecular classifications. Key topics included preoperative evaluation, neuraxis imaging, intraoperative strategies, extent of resection, histopathologic and molecular risk stratification, adjuvant radiotherapy and chemotherapy, recurrence patterns, and long-term surveillance. Representative clinical cases illustrating the surgical management of intramedullary spinal ependymomas and myxopapillary ependymomas are provided in the supplementary material.

Spinal ependymomas encompass spinal ependymoma, spinal ependymoma with MYCN amplification, spinal subependymoma, and spinal myxopapillary ependymoma. The primary therapeutic goal is maximal safe gross total resection, which is the most consistent modifiable predictor of progression-free survival. Molecular classification enhances risk stratification, especially for the aggressive MYCN-amplified subgroup. However, histologic grade and the extent of resection remain critical to management. Adjuvant radiotherapy is generally recommended for cases involving subtotal resection, grade 3 disease, tumor dissemination, capsular violation in myxopapillary tumors, or high-risk biology. Chemotherapy does not have a well-established role as a first-line treatment. Much of this evidence is extrapolated from adult or mixed-age cohorts, however, and pediatric-specific data remain limited across nearly every management domain, a gap we characterize systematically.

Management of spinal ependymomas is centered around surgery and adapted to individual risk factors. Overall survival is generally favorable for spinal ependymomas, but recurrence risk remains substantial and varies by extent of resection and molecular subtype. Lifelong surveillance is crucial, as both local recurrence and craniospinal dissemination may occur long after treatment.

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.