Glioblastoma is a grade 4 diffuse astrocytic glioma that is the most aggressive brain malignancy, with poor treatment outcomes and median overall survival (OS) of 10-14 months. Glioblastoma is characterized by upregulation of NAD metabolism, required to maintain rapid proliferation and DNA repair. Nicotinamide phosphoribosyltransferase (NAMPT), is the rate limiting enzyme in the NAD salvage pathway, and has emerged as a promising target in the treatment of glioblastoma. Previously, we reported the crucial role of adaptor protein TRAF3IP2 in glioblastoma tumorigenesis. In this study, we aim to investigate the role of TRAF3IP2 in modulating NAMPT expression and explore its downstream impact on promoting cellular energetics in glioblastoma cells. Our results reveal that inhibition of TRAF3IP2 in glioblastoma cells attenuates metabolic activity, as evidenced by decreased expression levels of NAMPT and the mTOR complex, leading to reduction in NAD synthesis and glycolytic function, decreased expression of NAD-dependent deacetylase SIRT1, and increased presence of cellular ROS and expression of tumor suppressor p53, cumulatively resulting in decreased cell viability in glioblastoma. These outcomes elucidate that inhibition of TRAF3IP2 exerts significant anti-tumor effects on glioblastoma by reducing NAD availability and cancer-cell metabolism, highlighting the therapeutic potential of TRAF3IP2 in glioblastoma.

This study aims to investigate the diagnostic accuracy of prostate health index (PHI) in combination with multi-parametric magnetic resonance imaging (mpMRI) for the detection of prostate cancer (PCa). Furthermore, the study also seeks to evaluate the diagnostic performance of this combined approach across various PSA levels, with the goal of developing a personalized biopsy protocol.

This retrospective study enrolled 120 patients who underwent PSA, PHI, and mpMRI tests prior to prostate biopsy and were divided into the PCa group and the benign prostatic hyperplasia (BPH) group. Patients with ISUP >2 were classified as clinically significant prostate cancer (csPCa). MpMRI images were interpreted according to the Prostate Imaging Reporting and Data System, version 2. Diagnostic accuracy of each indicator was assessed using receiver operating characteristic (ROC) curve analysis. Independent predictors were identified through univariate and multivariate logistic regression analyses. Furthermore, the diagnostic performance of PHI, mpMRI, and their combination was evaluated.

Based on the pathological biopsy results, 48 (40%) were diagnosed with PCa, while 72 (60%) patients had a benign lesion. The area under the curve (AUC) of PHI and PI-RADS score for PCa diagnosis was 0.747 and 0.790, respectively, both significantly higher than that of PSA (0.645) (p < 0.05). When PHI and PI-RADS score were used in combination, the sensitivity and specificity for PCa diagnosis were 81.3% and 68.1%, respectively.. Compared to the use of PSA, PHI or PI-RADS score alone, the specificity is enhanced while maintaining comparable sensitivity, potentially avoiding 50 (69.4%) cases of negative biopsies. Subgroup analysis stratified by PSA level showed that: (1) In the PSA ≤ 10 ng/ml subgroup, the AUC of PHI, PI-RADS score and PSA for PCa diagnosis was 0.698, 0.753 and 0.587 respectively, (p < 0.05). When the PHI and PI-RADS score are used in combination, the diagnostic sensitivity and specificity are 75.0% and 71.2%, respectively, which are superior than those of using either indicator alone; (2) In the PSA>10 ng/ml subgroup, PHI did not provide additional diagnostic benefits when used combined with PI-RADS score, with a diagnostic sensitivity of 65.0% and specificity of 90.0%. Correlation analysis of clinical indicators revealed that PHI was significantly correlated with PI-RADS score, Gleason score, and the number of positive biopsy cores.

This study demonstrates that PHI outperforms PSA in detecting PCa, with elevated PHI levels correlating with more advanced disease. Furthermore, combining PHI with mpMRI significantly enhances the detection rate of PCa, particularly among patients with low PSA levels.

Recent studies show that glioblastoma (GBM) is more sensitive to temozolomide (TMZ) in the morning. In cells, inhibiting O6-Methylguanine-DNA-Methyltransferase (MGMT) abolished time-dependent TMZ efficacy, suggesting that circadian regulation of this DNA repair enzyme underlies daily TMZ sensitivity. Here, we tested the hypotheses that MGMT promoter methylation and protein abundance vary with time-of-day in GBM, resulting in daily rhythms in TMZ efficacy.

We assessed daily rhythms in MGMT promoter methylation in GBM in vitro and retrospectively analyzed MGMT methylation status in human GBM biopsies collected at different times of day. Next, we measured MGMT and BMAL1 protein abundances in GBM cells collected at four-hour intervals. To understand the therapeutic implications of circadian variations in MGMT, we incorporated its daily rhythms into an in vitro mathematical model capturing interactions between MGMT, TMZ, and GBM DNA.

We found daily rhythms in MGMT promoter methylation and protein levels in GBM in vitro, and in patient biopsies peaking at midday. Further, MGMT protein levels peaked at CT4, corresponding to the time of maximal TMZ efficacy in vitro. When we incorporated cell-intrinsic circadian rhythms in MGMT protein into a mathematical model for GBM chemotherapy, we found that dosing when daily MGMT levels peaked and began to decline produced maximum DNA damage.

Our findings suggest that the likelihood of diagnosis of MGMT promoter methylation may vary with time of biopsy in GBM. Furthermore, theoretical modeling predicts that efforts to deliver TMZ after the daily peak of MGMT activity, with exact time being dose-dependent, may significantly enhance its therapeutic efficacy.

Overall side-effect impact, the aggregated experience of multiple toxicities, can be captured with the single Functional Assessment of Cancer Therapy (FACT) item GP5 ("I am bothered by side effects of treatment"). The objective of this study was to evaluate the ability of item GP5 to indicate treatment tolerability by examining its association with early treatment discontinuation (ETD) due to adverse events (AEs) in four cancer trials.

The authors analyzed data from four clinical trials coordinated by the ECOG-ACRIN Cancer Research Group, covering breast cancer (E1Z11, all patients received anastrozole; E1Z03, compared anastrozole vs. exemestane), melanoma (E1609, compared ipilimumab vs. high-dose interferon α), and chronic lymphocytic leukemia (E1912, compared ibrutinib-rituximab bs. standard chemoimmunotherapy). In each trial, GP5 responses were categorized as severe bother (i.e., "very much"/"quite a bit") versus moderate/low bother ("somewhat"/"a little bit"/"not at all").

At 3 months, significant associations were observed in each trial, indicating approximately 2.8-6.8 times greater odds of ETD among patients reporting severe bother (E1Z03: adjusted odds ratio [aOR], 2.82; 95% confidence interval [95% CI], 1.10-7.28; E1Z11: aOR, 4.10; 95% CI, 1.69-10.00; E1609: aOR, 6.77; 95% CI, 2.88-15.92; E1912: aOR, 4.15; 95% CI, 1.64-10.49).

These results support prior research demonstrating an association between severe side-effect bother, as reported on responses to the GP5 item, and ETD among patients with newly diagnosed multiple myeloma. The consistent association between GP5 responses and ETD suggests the GP5's ability to capture how well patients tolerate treatment, especially when side-effect bother is observed early in the course of treatment, and signals an opportunity to develop interventions to promote treatment adherence.

Decision regret (DR) (distress or remorse after a treatment decision) has received limited examination in older adults with advanced cancer. The authors hypothesized that DR would change over time and be associated with worse patient-reported outcomes (PRO) and clinician-rated tolerability metrics over 6 months.

Adults aged 70+ with advanced cancer planning to receive systemic treatment were recruited from a national trial (GAP70+, NCT02054741). DR level (none (0), mild [1-25], and moderate/severe [>25]) and PROs (symptoms, functional status, and satisfaction with treatment) were assessed at 4-6 weeks, 3 months, and 6 months after treatment initiation and compared with ANOVA. Associations between clinician-rated grade >3 toxicities, and treatment-related hospitalizations and DR were examined with longitudinal linear mixed modeling.

Data from 623 patients (M = 77 years, 43% female, mixed diagnoses) who completed the DR scale at least once were analyzed. At 4-6 weeks, mean DR was 17.1 (SD = 15.7), with 50% reporting mild DR and 21% moderate/severe DR. Patients experiencing higher DR reported significantly higher concurrent symptom severity, lower functional scores, and lower treatment satisfaction (all p < .05). At 6 months, mean DR was 3.9 points higher (95% confidence interval [CI], 1.1-6.7, p = .006) in patients with any grade >3 toxicities and 6.8 points higher (95% CI, 3.4-10.2, p < .001) in patients with treatment-related hospitalization.

DR changes over time and is associated with worse PROs and clinician-rated toxicity. Clinicians can discuss DR and poor tolerability in conversations about high-risk cancer treatment with older adults who have advanced cancer.

NCT02054741.

The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed by the US National Cancer Institute to allow patients to directly report their side effects, enhancing the accuracy and patient-centeredness of cancer clinical trial adverse event reporting. Clinician-based reporting often misses the full range of patient symptoms, resulting in underreporting of side effects. The selection of adverse events for patient reporting must be defined in advance and consistently applied across all study arms. Investigators can use core symptom sets, including diarrhea, fatigue, and nausea, alongside tailored items specific to the treatments being studied. PRO-CTCAE has demonstrated similar scores across electronic, paper-based, and automated telephone administration methods. PRO-CTCAE administration typically occurs before start of treatment and regularly throughout treatment, with the administration frequency tailored to the expected trajectory of side effects. Ensuring high survey completion rates is essential for PRO-CTCAE success. Standard reporting can include tabular reporting of the proportion of patients with any (score ≥1) and high (score ≥3) levels of symptoms at the individual item level. A baseline-adjustment approach should be applied to account for symptoms before start of treatment to isolate treatment-emergent adverse events. The distribution of PRO-CTCAE scores at each time point can be visualized using stacked bar charts. PRO-CTCAE integration into cancer clinical trials is crucial for capturing a comprehensive range of treatment-related symptomatic adverse events and improving the evaluation of therapy tolerability. Ongoing research continues to refine its implementation, supported by regulatory guidance.

To evaluate the prognostic role of pan-immune-inflammation value (PIV) in patients with oesophageal squamous cell carcinoma (ESCC) receiving chemoradiotherapy (CRT) combined with anti-programmed cell death 1 (PD-1) immunotherapy, and to explore the underlying mechanisms and dosimetric parameters that affect PIV zenith.

In this pooled analysis, 86 patients from two phase II trials who received toripalimab plus CRT were analysed. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The optimal cut-off value was determined using the receiver operating characteristic curve. Survival analysis was conducted using the Kaplan-Meier method and Cox regression models. Univariate and multivariable logistic regression analyses identified predictors of high PIV zenith. Pretreatment tumour samples from 46 patients were subjected to RNA and whole-exome sequencing (WES). Gene set enrichment analysis was performed on RNA sequencing (RNA-seq) data, and somatic mutations were assessed using WES to further explore molecular correlates.

Significant changes in immuno-inflammatory biomarkers were observed during CRT, which gradually normalized post-radiotherapy. After a median follow-up of 35.5 months, patients with high PIV zenith during CRT exhibited significantly poorer progression-free survival (p = 0.007) and overall survival (p = 0.015). In multivariable analysis, high PIV zenith remained a significant prognostic indicator for survival. Mean lung dose (MLD) was identified as an independent predictor of high PIV zenith. Patients with high PIV zenith had decreased interferon α response, interferon γ response, transforming growth factor-β signalling and more frequent mutations in the Hippo pathway genes, resulting in pathway downregulation.

High PIV zenith during CRT strongly predicts poorer survival outcomes in patients with ESCC treated with combined immunotherapy and CRT. These peaks are associated with higher MLD, reduced interferon α response, interferon γ response and increased prevalence of Hippo pathway mutations.

To assess the occurrence of oral mucositis in Chinese patients with cancer undergoing treatment and analyze its influencing factors.

From November 2023 to March 2024, a survey of 208 patients with cancer was conducted.

Data were collected through survey questionnaires and salivary pH testing. Demographic characteristics were analyzed using descriptive statistics. The Mann-Whitney U test was used to compare mucositis occurrence, and ordered logistic regression was used to identify predictive factors.

Among 208 surveyed patients, 56 (27%) experienced oral mucositis, with severity grades distributed as follows: grade 1 (n = 37, 18%), grade 2 (n = 12, 6%), and grade 3 (n = 7, 3%). Salivary pH level, dry mouth, mouth rinsing, and primary disease were identified as key factors.

Chinese patients with cancer have a high occurrence of oral mucositis. Lower salivary pH levels and higher dry mouth scores increase the risk. Oncology nurses can prioritize early preventive strategies, salivary pH testing and xerostomia assessment, and targeted hygiene guidance. A risk-stratified prevention model can be implemented to enable precision management of oral mucositis.

To investigate the mediating effect of self-efficacy (SE) on the relationships among patient-provider partnership (PPP), pain, and quality of life (QOL) in individuals with cancer.

Individuals with cancer were recruited online through cancer organizations and social media support groups in 2023.

This cross-sectional survey collected data on demographic/clinical characteristics, cancer pain outcomes, PPP, SE for cancer pain management, and QOL. Mediation analyses assessed the role of SE in the relationships among PPP, pain, and QOL.

Most participants were female, White, and aged 18-60 years. SE mediated the relationships between PPP and pain severity, pain interference, QOL function, and QOL symptoms. Greater PPP was associated with higher SE.

A supportive PPP is essential for improving pain outcomes and QOL in individuals with cancer by strengthening their SE.

To assess whether the use of patient-reported outcomes (PROs) is associated with patient empowerment (PE) in cancer survivors in early survivorship.

A convenience sample of 83 adult cancer survivors participated in a quantitative repeated-measures study at a community-based cancer center, and 33 participants who received chemotherapy as the last treatment modality of their primary cancer treatment completed a questionnaire immediately following treatment and at three months.

Participants were recruited from the medical oncology clinic by oncology nurse research assistants and completed an electronic or paper survey composed of three instruments.

A significant relationship was found between PE and self-efficacy, and a significant negative correlation was observed between self-efficacy and symptoms. PRO self-efficacy predicted PE following chemotherapy treatment. PE decreased at three months post-treatment.

Clinician-driven assessment is less sustainable in survivorship care. The use of PROs for symptoms and self-efficacy is related to PE. A qualitative study for conceptual clarification of PE in cancer survivors is needed. Oncology nurses are key to envisioning how to implement survivor-reported symptom assessment that builds empowerment.