We evaluated whether CT intensity and texture radiomics provide predictive value beyond simple volume dynamics for lesion-level response prediction in metastatic melanoma treated with immune checkpoint inhibitors.

We conducted a retrospective multicenter study including 158 patients (1,626 lesions) from an internal cohort (n = 129 patients with standardized protocols) and an external cohort (n = 29 patients with heterogeneous protocols). The primary endpoint was binary lesion-level size response (clinical benefit vs. progressive disease) at the second follow-up. We trained and compared Random Forest classifiers to predict this endpoint using clinical variables, volumetric features, radiomics, and combined predictors derived from baseline and first follow-up imaging. Models were trained on the internal cohort using patient-grouped cross-validation and applied unchanged to the external cohort. Paired differences in AUC were assessed against a ± 0.05 equivalence margin.

Baseline-only prediction of first follow-up response was near chance for all models. For predicting response at second follow-up, the volumetric model achieved an internal AUC of 0.84 [95% CI 0.78-0.88] and the radiomics model 0.86 [0.81-0.90]. In the external cohort, with 12 progression events, the volumetric and radiomics models achieved AUCs of 0.68 [0.50-0.85] and 0.68 [0.51-0.88], with no significant difference between any models. Organ-specific analysis showed no significant improvement from adding radiomics for any lesion site. Across all 288 radiomic features, the median absolute correlation with lesion volume was 0.37. Sensitivity analyses contained small or borderline gains that did not replicate externally.

Volumetric features capture the primary predictive information for early lesion-level response, and CT radiomics showed no conclusive improvement over volume dynamics. Confirmation in larger independent cohorts is required before radiomic signatures can be recommended for this task.

Not applicable.

Distinguishing prostate cancer (PCa) from benign prostatic tissue can be challenging in equivocal cases. Gleason grading remains the gold standard, with immunohistochemical (IHC) markers such as androgen receptor (AR), prostate-specific antigen (PSA), and α-methylacyl-CoA racemase (P504S/AMACR) serving as established adjuncts. This study aimed to confirm their diagnostic utility in a retrospective Chinese cohort of PCa and benign controls (primarily benign prostatic hyperplasia [BPH]).

This retrospective analysis included 147 patients (88 PCa, 59 BPH) evaluated between 2020 and 2024 at two Chinese institutions. Gleason scores were extracted from pathology reports. IHC for AR, PSA, P504S (AMACR), and hematopoietic cell kinase (HCK) was performed routinely when clinically indicated. AR staining (when available) was assessed exclusively in tumor cell nuclei, with positivity defined qualitatively by any discernible nuclear staining (typically >1% of cells, including weak intensity). Due to the retrospective design and routine practice, no uniform cutoff or re-scoring was applied. AR and PSA results were available in most cases, whereas P504S was assessed in a subset (40/88 PCa; 19/59 benign), typically diagnostically ambiguous samples. Marker positivity was compared between PCa and benign tissue and correlated with Gleason score components and patient age.

AR and PSA positivity were significantly higher in PCa than benign tissue (AR: 25.0% vs. 8.5%, p=0.011; PSA: 40.9% vs. 20.3%, p=0.009), consistent with prior reports. The lower AR rate in PCa (25.0%) likely reflects routine clinical reporting variability and thresholds. In assessed subsets, P504S was positive in 100% (40/40) of PCa cases versus 26.3% (5/19) of benign cases (p<0.0001), aligning with its established sensitivity. AR positivity peaked in intermediate Gleason grades but declined in high-grade tumors, while PSA showed a modest increasing trend with grade. HCK was uniformly negative in all assessed cases, supporting its limited diagnostic relevance. No significant age association was observed with Gleason categories.

This retrospective analysis corroborates the complementary roles of P504S (in assessed subsets), AR, and PSA as valuable IHC adjuncts to Gleason grading for evaluating prostate tissue, including differentiation from benign conditions such as BPH. HCK negativity further supports its deprioritization in diagnostic panels.

The caregiving experience can have a significant impact on family caregivers' (caregivers) health and well-being, particularly those of patients with advanced cancer. Interventions to support caregivers through health-promoting strategies are needed. The physical and psychological benefits of physical activity (PA) are well documented, yet the value of PA for caregivers of people with advanced cancer is not well understood. To address this gap, a home-based individually tailored PA intervention was designed with the aim of increasing caregivers' positive affect and health and decreasing their negative affect and fatigue. The objective of this study was to explore the acceptability of the intervention for caregivers.

A descriptive exploratory qualitative research design was used. Caregivers (N = 10) were recruited to participate in the intervention for 6 weeks and provided weekly qualitative feedback on its structure and process. A follow-up individual interview was conducted with caregivers to solicit their overall experience with the intervention. Data were analyzed using content analysis.

Eight of 10 caregivers completed the intervention. Caregivers deemed the PA intervention to be acceptable. No modifications were necessary other than slight changes in formatting to the PA log. Caregivers were appreciative of attention to and support of their own self-care. A home-based PA program allowed them to take breaks from caregiving responsibilities while staying near the patient. Individually tailored PA, goal setting and self-monitoring were helpful for caregivers to engage in and adhere to their PA plans. In addition, weekly telephone calls for feedback and support helped to problem solve any barriers and provided motivation. Given that caregivers often chose to engage in smaller, more frequent bouts of PA, the intervention was named My Ten.

The My Ten PA intervention is acceptable to caregivers of those with advanced cancer, helping them to engage in and adhere to PA as a health-promoting strategy.

In this phase II trial, patients with endometrial cancer (EC) were randomized to everolimus/letrozole with (experimental arm) or without ribociclib (control arm) (ClinicalTrials.gov Identifier: NCT03008408). The primary endpoint was progression-free survival (PFS). Secondary endpoints included toxicity, overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). For all-comers, there was no difference in PFS (HR 0.78, 95% CI 0.4-1.4, p = 0.38), OS (HR 0.8, 95% CI 0.4-1.5, p = 0.46), ORR (44.1% vs 25.7%, p = 0.11), or toxicity-related treatment discontinuation (4 [8.6%] vs 3 [11.4%], p = 0.22). Among those with prior endocrine therapy, ORR was higher in the experimental arm (61.5% vs 0.0%, p < 0.001). Within the experimental arm, CTNNB1_mut tumors were associated with improved PFS (HR 0.27, 95% CI 0.1-0.7, p = 0.006) and OS (HR 0.24, 95% CI 0.1-0.7, p = 0.004) compared to those with non-CTNNB1_mut tumors. Despite no survival improvement in all-comers, addition of ribociclib to everolimus/letrozole may improve efficacy in patients with prior endocrine therapy and cases with CTNNB1_mut tumors may have prolonged response.

Observational, descriptive and retrospective study.

This article's objective is to analyze the epidemiological characteristics, anatomical distribution, and functional status of persons with vertebral tumors treated at a tertiary care center in an emerging country between 2019 and 2023.

January 1, 2019, to December 31, 2023 (5 years), at the Department of Peripheric Nerve, Traumatology and Orthopedic Hospital "Dr. Victorio de la Fuente Narváez", Mexico City, Mexico.

It was conducted an observational descriptive and retrospective study analyzing 358 persons with confirmed vertebral tumors. All cases were evaluated using the ASIA/ISCoS International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) worksheet at admission. Histopathological diagnosis, anatomical location, healthcare level at diagnosis, and ASIA Impairment Scale (AIS) were analyzed using descriptive statistics.

Of the 358 cases analyzed, 88% were malignant lesions, with metastatic tumors-especially from breast, prostate, and kidney-being the most common. The thoracic spine was the most frequently affected region (47.2%). AIS D (moderate motor deficit) was the most prevalent classification (46.6%). Emergency department diagnoses increased over the study period, from 24.4% in 2019 to 57% in 2023, while referrals from primary and secondary care declined. Malignant tumors predominated in persons aged 41-80, while benign tumors were more frequent in younger persons.

Most vertebral tumors were diagnosed at advanced stages and in emergency settings, suggesting a need to improve early detection and referral systems. Enhanced training and integration across healthcare levels are essential to optimize outcomes in individuals with vertebral tumors in resource-limited settings.

No funding sources influenced the design, execution, or interpretation of the research presented in this article.

Homologous recombination deficiency (HRD) has been reported to be associated with increased sensitivity to platinum-based treatment and radiotherapy in some solid tumors.

This study investigated the correlation between HRD score and treatment response to neoadjuvant short-course radiotherapy combined with sequential chemotherapy and tislelizumab in mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC).

Thirty-two pMMR LARC patients from clinical trial NCT05515796 were enrolled. Pretreatment biopsy samples were analyzed for HRD scores and tumor immune microenvironment (TIME) gene expression profiles. Using receiver operating characteristic (ROC) analysis, patients were stratified into low (0-8), intermediate (9-37), and high (> 37) HRD score groups to compare pathological complete response (pCR) rates. Abundance of immune cells and immune-related pathways were assessed with MCPcounter and single sample gene set enrichment analysis (ssGSEA) respectively and compared among the three HRD score groups. The entire cohort demonstrated pCR rate of 40.62% (13/32) with a median HRD score of 9 (range: 0-70). ROC analysis showed that HRD score as a continuous variable did not reach statistical significance in distinguishing pCR patients from non-pCR patients, nor did TMB and HR mutation. However, the proportion of categorized HRD score was significantly different between pCR and non-pCR groups (low, intermediate, high HRD score: 61.54%, 23.08%, 15.38% vs. 31.58%, 68.42%, 0%, p = 0.017). High-HRD tumors exhibited the highest CD8+ T-cell abundance followed by low-HRD and intermediate-HRD groups.

HRD score may be associated with efficacy of neoadjuvant radioimmunotherapy in pMMR LARC patients, potentially mediated through enhanced CD8+ T-cell recruitment. These findings support precision patient selection, though mechanistic validation is required.

BACKGROUNDSmall-cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis and marked transcriptional heterogeneity that may drive distinct therapeutic vulnerabilities. Clinical translation of molecular subtyping has been limited by restricted access to tumor biopsies, particularly at relapse.METHODSWe applied chromatin immunoprecipitation of cell-free nucleosomes carrying active histone modifications followed by sequencing (cfChIP-seq) to 441 plasma samples from individuals with advanced SCLC, other neuroendocrine carcinomas, or non-SCLC cancers, as well as from healthy controls. Plasma cfChIP-seq profiles were integrated with matched tumor transcriptomes from 73 samples, including 41 time-matched pairs.RESULTScfChIP-seq captured the epigenetic and transcriptional landscape of tumor-derived cell-free DNA (cfDNA), including SCLC tissue- and cell-of-origin signatures. A quantitative cfChIP-seq-derived SCLC score tracked radiographic tumor burden and was associated with prognosis. Signals at promoters of lineage-defining transcription factor genes, including ASCL1, NEUROD1, POU2F3, and ATOH1, correlated strongly with matched tumor RNA expression and supported noninvasive inference of SCLC transcriptional subtypes directly from plasma.CONCLUSIONPlasma cfChIP-seq provides a practical liquid biopsy platform for real-time assessment of tumor burden, tumor state, and molecular subtype in SCLC. These findings support further development of cfChIP-seq for precision monitoring and subtype-informed therapeutic stratification in SCLC.TRIAL REGISTRATIONClinicalTrials.gov NCT02484404, NCT02487095, NCT02769962, NCT03554473, NCT03896503, and NCT02146170.FUNDINGCenter for Cancer Research; Intramural Program of the NCI (ZIA BC 011793); European Research Council (ERC) (Adg no. 101019560 "cfChIP").

Bladder-preserving therapies are increasingly important for patients with bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS) who are unfit for or decline radical cystectomy. Because sustained complete response (CR) is critical for bladder preservation, we compared duration of response (DoR) among CR responders treated with TAR-200 or nadofaragene firadenovec using reconstructed individual patient data from published Kaplan-Meier curves.

Published DoR Kaplan-Meier curves for CR responders were digitized from SunRISe-1 cohort 2 evaluating TAR-200 monotherapy and from the phase III NCT02773849 CIS cohort evaluating nadofaragene firadenovec. Reconstructed individual patient data (rIPD) were reconstructed using IPDfromKM package. Restricted mean survival time (RMST) for DoR was estimated at 6, 12, 18, and 24 months. A Weibull mixture cure model was fitted as an exploratory analysis to estimate the durable CR fraction.

RMST differences for DoR between TAR-200 and nadofaragene firadenovec were not statistically significant through 24 months. RMST differences were -0.29 months at 6 months, -0.04 months at 12 months, +0.60 months at 18 months, and +1.34 months at 24 months, with confidence intervals crossing zero at all timepoints. In the exploratory Weibull mixture cure model, the estimated durable CR fraction was larger for TAR-200 than for nadofaragene firadenovec (0.521 vs. 0.256; difference +0.265).

In this exploratory rIPD-based cross-trial analysis, CR durability among responders did not differ significantly between TAR-200 and nadofaragene firadenovec through 24 months. Later RMST point estimates and model-based durable CR fraction estimates were numerically higher for TAR-200, but these findings require cautious interpretation because of cross-trial comparability limitations, responder-conditioned selection, and limited follow-up.

Immune-nutritional status and gut microbiota composition have been proposed as biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). However, their interrelationship and longitudinal dynamics during immunotherapy remain unclear.

In this multicenter prospective study, patients with advanced or recurrent NSCLC treated with atezolizumab-based immunotherapy were enrolled. Serial fecal samples were analyzed using 16S rRNA gene sequencing. Immune-nutritional status was evaluated using the prognostic nutritional index (PNI). Associations between baseline PNI, gut microbiota composition, treatment response, immune-related adverse events (irAEs), and longitudinal microbiota changes were assessed.

Sixty-five patients were included (27 responders and 38 non-responders). Pretreatment PNI was significantly associated with treatment response (p=0.0048) and improved progression-free and overall survival. During follow-up, 12 patients (18.5%) developed irAEs. Lachnospiraceae UCG-008 was enriched in patients with high PNI and in those without irAEs. Longitudinal analysis showed stable abundance of this taxon during treatment with no significant temporal changes.

Pretreatment gut microbiota composition was associated with immune-nutritional status and clinical outcomes in patients with NSCLC receiving atezolizumab-based immunotherapy. Lachnospiraceae UCG-008 was linked to favorable host status and lower irAE risk, remaining stable during treatment. These findings suggest that baseline gut microbiota may serve as a clinically relevant biomarker for both the efficacy and safety of immunotherapy.

BackgroundCervical cancer incidence remains higher among Latina women in the continental United States (US) and among women in Puerto Rico compared with non-Hispanic White women (NHW). Latinas remain more likely to die from cervical cancer than NHW women. Despite having one of the highest cervical cancer incidence rates, Latina women in the US are significantly less likely to undergo screening than NHW women. Multiple factors contribute to non-screening among Latinas including low access to healthcare services, racism/discrimination, and lack of culturally and linguistically adequate information. Emerging technologies supporting self-sampling for high-risk human papillomavirus (HPV) testing may offer a valuable evidence-based strategy for empowering Latinas to engage in cervical cancer screening.ObjectiveThis study aimed to develop a culturally tailored, theoretically grounded intervention to promote HPV self-sampling among underscreened Latinas.DesignThis was a community-engaged qualitative intervention development study informed by focus groups and Community Advisory Board (CAB) meetings with underscreened Latinas and community stakeholders.MethodsWe conducted three focus groups, two in English with 20 participants and one in Spanish with 10 participants. Further, we convened two CAB meetings with a community-advisory board of 10 community members, including clinicians and behavioral health providers. Triangulation of data from the focus groups and CAB meetings informed the development of Juntas Contra el Virus del Papiloma Humano, a three-session online bilingual English and Spanish intervention to promote self-sampling for HPV testing.ResultsWe discuss the development of a culturally tailored, theoretically grounded HPV self-testing intervention for underscreened Latinas and share the findings from our intervention development process. We describe the content of each session, our protocols, and best practices for engaging Latinas and CAB members.ConclusionIf Juntas Contral El Virus del Papiloma Humano is found to be effective, the intervention will reach a vulnerable population to encourage screening and reduce cervical cancer.