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To assess the effectiveness and safety of 5-aminolevulinic acid-based photodynamic therapy (5-ALA PDT) for cervical low-grade squamous intraepithelial lesions (LSIL) patients with high-risk human papillomavirus (HR-HPV) infection and to investigate independent factors that influence the efficacy of PDT treatment. A retrospective analysis was conducted on 530 patients with pathologically confirmed LSIL and HR-HPV infection, treated between March 2017 and January 2024. All patients underwent 5-ALA PDT at an interval of 7-14 days, for a total of 3 to 6 sessions. Follow-ups were conducted 3 and 12 months post-treatment. The efficacy was assessed using HPV genotyping, ThinPrep cytology test (TCT) and colposcopy-directed biopsy. The HPV remission rate was 52.08% at 3 months' follow-up and increased to 69.84% at 12-month follow-up, surpassing the rate at 3-month follow-up (p < 0.001). The LSIL regression rate was 75.85% at 3 months' follow-up and rose to 86.77% at 12-month follow-up, exceeding the rate at 3-months' follow-up (p < 0.001). Multivariate analysis revealed that single HPV infection (OR 2.296 [95%CI 1.550-3.402]) was an independent predictor of HPV remission after 5-ALA PDT treatment. Single HPV infection (OR 1.690 [95% CI 1.077-2.652]), type III transformation zone (OR 3.094 [95% CI 1.899-5.041]), HPV remission after PDT treatment (OR 4.938 [95% CI 3.099-7.870]) were independent predictors of LSIL participants receiving total lesion regression after PDT treatment. Adverse reactions were all mild. 5-ALA PDT is an effective and non-invasive therapy for LSIL patients with HR-HPV infection. Identifying predictors of treatment success may optimize patient selection, ultimately improving clinical outcomes.

The prognostic value of lesion distribution in renal cell carcinoma bone metastasis (RCC-BM) is unclear. This study aimed to quantify the association between BM distribution and prognosis in RCC-BM patients and to employ a predictive model based on the random survival forests (RSF) algorithm. At first BM diagnosis, 122 patients were stratified by Memorial Sloan-Kettering Cancer Center (MSKCC)/Motzer risk score and classified into locoregional (21.3%), stochastic (56.6%), and extensive (22.1%) groups based on bone lesion distribution. Spinal and pelvic involvement was observed in 39.3% and 35.2% of patients. Univariate, logistic regression, and Kaplan-Meier survival analyses indicated that locoregional spread, spinal involvement (odds ratio [OR] 3.30; 95% confidence interval [CI] 1.20-9.09), and advanced age (OR 1.04; 95% CI 1.00-1.08; p < .05) correlated with higher risk stratifications, while pelvic metastasis was linked to shorter median overall survival (32 vs. 49 months; p < .05). The RSF model was trained in 70% and validated in 30% of the series, incorporating spatial lesion involvement (pelvic, spinal, and upper extremities involvement), MSKCC/Motzer score, and age as principal contributing variables. Time-dependent area under the curve (AUC) values achieved in single-split validation for 1- and 3-year survival were 0.90 and 0.87. Consistent performance was observed across 100 repeated splits, with median AUCs of 0.89, 0.86, and 0.89 for 1-, 3-, and 5-year survival, respectively. A cut-off value of 15.03 effectively separated high- and low-risk groups (p < .05). RSF demonstrated superior accuracy over Cox regression (median AUC 0.89 vs. 0.59 for 1-year survival). Overall, integrating bone lesion patterns into RSF modeling facilitates personalized prognosis and supports more precise care in RCC-BM.

Cancer stigma negatively impacts diagnosis, quality of life, and survival outcomes, yet stigma reduction efforts are hindered by the lack of a valid and universal scale to measure cancer stigma. This study aimed to develop and validate a global cancer stigma scale, the Cross-Cultural Oncology Measure for Perception and Awareness of Stigma Scale (COMPASS), which measures internalized, anticipated, and enacted stigma. The scale was developed using mixed methods in two phases: (1) feedback from experts and people with cancer on an initial pool of items, and (2) psychometric validation with people with cancer. Data were collected from two cancer centers in Salt Lake City, Utah, USA, and Lilongwe, Malawi. We examined the scale's initial psychometric properties, including item-total correlation, reliability, factorial validity, and construct validity. Initial qualitative interviews informed the generation and refinement of 50 items, which were then administered to 209 individuals with cancer. Psychometric analysis reduced the scale to 28 items distributed across three stigma domains: anticipated (8 items), internalized (8 items), and enacted (12 items). The refined scale demonstrated satisfactory psychometric properties, with confirmatory factor analysis supporting a three-factor model fit (CFI = 0.859, RMSEA = 0.112, SRMR = 0.063) and strong reliability (Cronbach's alpha: 0.92 to 0.97). Validity was confirmed through strong correlations with related constructs. COMPASS offers a reliable, valid, and cross-culturally applicable tool to measure the magnitude and impact of cancer stigma globally and facilitate the evaluation of stigma reduction interventions.

The DNA methylation-based WID-qEC test, applied to cervico-vaginal samples, has been validated for the accurate detection of endometrial and cervical cancers. However, a small proportion of women test positive despite the absence of these cancers. The aim of this study was to explore the biological and clinical characteristics associated with such WID-qEC-positive cases to inform potential follow-up strategies. We analyzed 1269 cervico-vaginal samples from women without endometrial or cervical cancer, including healthy controls (n = 624), women with benign gynecological conditions (n = 324), and ovarian cancer cases (n = 321). Of the 80 WID-qEC-positive results, 43 (54%) were from women with ovarian cancer. WID-qEC positivity was associated with the presence of ovarian cancer (adjusted odds ratio [OR] 2.93; 95% CI 1.75-4.95) and with a higher number of lifetime ovulatory cycles (adjusted OR 2.67; 95% CI 1.06-7.50), a known ovarian cancer risk factor. Both associations were independent of age, menopausal status, hormone replacement therapy usage, or family history of breast or ovarian cancer. Our findings suggest that in the absence of endometrial or cervical cancer, WID-qEC positivity may indicate an elevated risk or presence of ovarian cancer. While the standalone positive predictive value (PPV) for ovarian cancer detection remains low in the general population, we outline how WID-qEC could be used in a two-step triage approach. In women presenting with abnormal bleeding, combining WID-qEC positivity with a highly specific plasma-based cell-free DNA methylation test (e.g., with 60%-80% sensitivity and ~98.4% specificity) could theoretically yield a PPV of around 30%-40%. This hypothetical modeling is intended solely to illustrate how WID-qEC positivity might inform future triage research, rather than to propose a clinical diagnostic algorithm.

Minimal residual disease (MRD) assessment using circulating nuclear DNA (cir-nDNA) testing has demonstrated strong prognostic value in patients with operable stage III colon cancer (CC). However, further clinical research is needed to optimize the use of adjuvant therapy in this context. Since the sensitivity of variant allele frequency (VAF)-based MRD detection depends on total cirDNA concentration, we investigated its variation in 67 stage III CC patients over 8 weeks following surgery. A majority of patients showed significantly higher post-surgical cir-nDNA levels compared to their pre-surgical baseline-71.1% during the first month and 51.4% during the second. Cir-nDNA levels tended to considerably vary (up to 18-fold), especially during the first 3 weeks after surgery. We also observed a strong correlation between cir-nDNA levels and neutrophil extracellular traps (NETs) markers throughout the 2-month post-operative period. While previous studies have generally assumed that cir-nDNA levels decrease significantly within 1 month post-surgery in MRD-negative stage III patients, our findings challenge this paradigm. NETs appear to be a substantial source of cir-nDNA and represent a major confounding factor in interpreting total cir-nDNA, given the high inter-individual variability in NETs production after surgery. Our data suggest that defining a single optimal time point for MRD testing may be misleading. Instead, we propose a sampling window between fourth and sixth week post-surgery. Additionally, our results call into question the reliance on VAF as a standalone metric for MRD detection. The most robust strategy would involve integrated monitoring of total cir-nDNA concentration, absolute mutant DNA levels, and NETs-associated inflammation.

Analyzing T-cell subsets in and between primary colorectal cancer (pCRC) and adjacent non-tumor mucosa (NM) may reveal distinct prognostic value in stage IV versus stages I-III patients. Specimens of pCRC and NM were collected retrospectively from stage IV patients (n = 55) with synchronous liver metastases (LM), and stages I-III patients (n = 44) who developed metachronous LM. CD3⁺, CD8⁺, CD45RO⁺, CD4⁺, and Foxp3⁺ T-cells were quantified in NM and the tumor center (TC) of pCRC using immunohistochemistry. T-cell densities in NM and TC and their ratios (TC/NM) were tested as prognostic variables for overall survival (OS), along with Foxp3⁺/CD8⁺, Foxp3⁺/CD4⁺ and CD4⁺/CD8⁺ ratios. In stages I-III, associations with the time to occurrence of LM were also evaluated. In both groups, NM exhibited greater densities of CD3⁺, CD8⁺, CD45RO⁺, and CD4⁺ cells compared to TC, whereas Foxp3⁺ cells were more abundant in the TC. In stage IV, high densities of Foxp3⁺ cells, high Foxp3⁺/CD4⁺ and Foxp3⁺/CD8⁺ ratios in the NM, and high CD4⁺ cell densities in the TC were associated with longer OS. Stages I-III patients with a high CD4⁺/CD8⁺ ratio in the NM had longer OS, whereas a high Foxp3⁺/CD8⁺ ratio in the TC was associated with a shorter time to LM. We revealed a significant difference in the T-cell landscape between pCRC and adjacent NM with Foxp3⁺ cells predominating in the TC and other subsets in the NM. Assessing T-cells and their ratios in both regions may improve prediction of survival in CRC patients and the time to LM in stages I-III.

Breast cancer (BC) is the most common malignancy in women worldwide and has a significant impact on younger populations. This study analyses incidence and survival by grade of histological differentiation, molecular subtype, stage at diagnosis and socioeconomic deprivation in young women diagnosed with BC in 2018 in the Community of Madrid (CM) followed up to 2023. Data from invasive BC cases in women aged 20-49 were obtained from the Population-Based Cancer Registry of the CM. Descriptive analyses were conducted for sociodemographic and tumour characteristics. Crude, age-specific and age-standardised incidence rates were calculated. For survival analysis, observed, net and age-standardised net survival using the international cancer survival standard weights were estimated at 1, 3, and 5 years. Flexible parametric models were adjusted to determine differences in the risk of death by molecular subtype. In 2018, 1049 invasive BC cases were registered among 1,432,392 women aged 20-49. The age-standardised BC incidence rate computed was 66 cases/100,000 women-year. Luminal B was the most frequent subtype with 22.9 cases/100,000 (95% CI: 20.6-25.4). Stages I and II had the highest age-standardised incidence rates. Women in less deprived areas showed the highest crude incidence rate: 100.3 cases/100,000 women-year. The 5-year observed survival was 94.8% (95%CI: 93.2-95.9). Poorly differentiated tumours (grade III), triple negative subtype and stage IV at diagnosis had the lowest survival estimates. No significant differences in survival were observed across deprivation status. This study offers comprehensive epidemiological insights into BC incidence and survival in young women in Madrid, offering support for clinical decision-making and prognosis assessment.

A circulating tumor DNA (ctDNA) assay for methylated BCAT1/IKZF1 can detect rectal adenocarcinoma, but its efficacy after neoadjuvant chemoradiotherapy-commonly used for patients with rectal cancer-is unknown. We determined the effect of radiation treatment on BCAT1/IKZF1 methylation in colorectal cancer (CRC) cell lines and rectal cancer tissues, and determined the value of a ctDNA assay measuring methylated BCAT1/IKZF1 for accurately assessing response to neoadjuvant chemoradiotherapy in patients with rectal cancer. Proof-of-principle experiments assessed CRC cell lines for BCAT1/IKZF1 methylation after irradiation and 5-fluorouracil treatment. Tissue and pre-surgical blood samples were collected from 34 patients diagnosed with rectal cancer, following or without any neoadjuvant treatment, and assayed for BCAT1/IKZF1 DNA methylation using multiplex qPCR. Tissues were scored for histological response, with BCAT1/IKZF1 DNA methylation compared between untreated patients, poor responders, and good responders. Radiation treatment did not affect BCAT1/IKZF1 methylation of CRC cells in vitro. BCAT1/IKZF1 methylation reduced in rectal adenocarcinoma tissues in response to neoadjuvant treatment. Tumor tissue from good responders contained low levels of methylated BCAT1/IKZF1, equivalent to matched normal tissue. The methylated BCAT1/IKZF1 assay had 87% (13/15) sensitivity for rectal cancer in untreated patients. Reduced methylated BCAT1/IKZF1 ctDNA levels were correlated with neoadjuvant therapy-related tumor regression. Radiation does not affect BCAT1/IKZF1 methylation in cancer cells, independent of treatment response. Reduced BCAT1/IKZF1 methylation in rectal tumors and plasma ctDNA reflects reductions in tumor cellularity. These data support future investigations to use methylated BCAT1/IKZF1 ctDNA for monitoring response to neoadjuvant therapy in patients with rectal cancer.

Pancreatic cancer (PCA) is the third leading cause of cancer-related death in Europe. Despite recent therapeutic advances, patients experience rapid health deterioration. Based on previous results, the Platform for Outcome, Quality of Life, and Translational Research on Pancreatic Cancer-PARAGON (NCT04119362) was initiated to investigate the whole life cycle of PCA patients. Between November 2019 and October 2021, 469/479 screened patients were enrolled in 46 sites. Demographic, clinical, and quality of life (QoL) data were collected. The treatment landscape was depicted using Sankey diagrams. Median overall survival (mOS) for all patients in first line was 10.6 months (95% confidence interval [CI], 9.2-11.7 months). With mFOLFIRINOX as first-line treatment, mOS was 11.3 months (95% CI, 8.6-13.5 months), with gemcitabine/nab-paclitaxel 10.5 months (95% CI, 8.3-12.9 months). The mean Global Health Status for patients that proceeded from first to second line did not substantially deteriorate during first line. Predictive variables for proceeding from first to second-line therapy were reasons for ending first-line treatment (patient's wish, toxicity, and progressive disease) and age. In summary, we were able to show in detail patient flows and QoL data throughout all therapy lines, which will help to further understand the major clinical checkpoints of the disease.

Most cutaneous malignant melanomas (CMMs) are thin (≤1.0 mm, stage T1) with an expected 10-year melanoma-specific survival of 93%-97%. The incidence of CMM is higher in groups with high socioeconomic status (SES). We aimed to assess overall survival (OS) and detailed characteristics in individuals with thin CMM as compared to the general population matched on age, sex, and county of residence. Matched cohort study comprising patients diagnosed between 2001 and 2018 with thin CMM (cases) and melanoma-free comparators from the general population. Patients and comparators were identified in the Malignant Melanoma Data Base Sweden. Multivariable Cox regression analyses were applied to compare the mortality risk for cases and comparators with adjustments for SES and comorbidities. We identified 25,843 cases and 127,383 comparators. Cases had higher SES and less comorbidity. No significant differences in OS were found. However, in the T1a subgroup, comprising 16,941 cases, the 5-year OS was significantly better than in comparators (n = 83,510) (92.5% (95% CI 92.1%-93.0%) versus 91.1% (95% CI 90.8%-91.3%), p <.001). The adjusted mortality risk was slightly higher for the whole T1 group (HR 1.05, 95% CI 1.01-1.09), while no difference was found for the T1a subgroup. Deaths attributed to cardiovascular disease, dementia, and chronic obstructive pulmonary disease were less common in CMM patients. Patients diagnosed with thin CMM have an OS similar to or even better than the general population since they are at a lower risk of death from other diseases, likely reflecting socioeconomic and lifestyle factors.