Cancers最新文献

Background/Objectives: Molecular subtyping of pediatric B-cell acute lymphoblastic leukemia (B-ALL) has improved patient outcomes through stratification and selection of targeted therapies. Despite extensive genomic and transcriptomic profiling of this cancer, few studies to date have characterized the proteomic landscape, although proteins are the direct targets of many therapeutic agents. Methods: In this study, we demonstrate the utility of multi-omic integration of global transcriptomic, proteomic, and phosphoproteomic profiles of samples from patients diagnosed with either of two B-ALL subtypes-Ph-like (BCR::ABL1-like) and ETV6::RUNX1. Through individual and multi-omic analysis, we recapitulate known transcriptomic findings and identify novel subtype-specific proteomic and phosphoproteomic biomarkers. Conclusions: Our findings suggest a previously undescribed role for calcium-dependent signaling processes in Ph-like B-ALL, which has the potential to serve as a novel avenue for targeted treatments. By integrating multiple -omics modalities, we identify not only features of interest but also begin to unravel the regulatory interactions driving subtype-specific mechanisms of leukemogenesis. This integrated analytic approach paves the way for enhanced precision medicine for precise subtyping and treatment selection for pediatric leukemia patients.

Background/objectives: Treatment delays have been shown to be associated with overall survival (OS) in head and neck squamous cell carcinomas (HNSCCs). Given the slow tumor growth kinetics of adenoid cystic carcinoma (ACC), it is unclear if delays have a similar impact in this tumor histology.

Methods: We queried the National Cancer Database for patients diagnosed with non-metastatic ACC between the years 2004 and 2019 and treated with surgery followed by RT. A multivariable Cox regression model was used to examine the associations between the time from diagnosis to surgery, the duration of RT, and OS.

Results: A total of 1449 patients were included for analysis. Increased time from diagnosis to surgery (HR: 1.02, 95% CI: 1.01-1.03, p < 0.001) and duration of RT (HR: 1.14, 95% CI: 1.04-1.25, p = 0.004) were associated with worse survival on UVA, while time from surgery to RT start was not (p = 0.647). Increased duration of RT (aHR: 1.13, 95% CI: 1.03-1.24, p = 0.012) remained significantly associated with OS on multivariable analysis, while time from diagnosis to surgery (aHR: 1.00, 95% CI: 0.98-1.02, p = 0.979) did not.

Conclusions: Delays in treatment initiation and in the interval from surgery to radiation did not result in clinically significant differences in survival in this analysis, while prolonged duration of radiation therapy was significantly associated with worse survival. These findings are hypothesis-generating and suggest that treatment delays for ACC may have different effects on oncologic outcomes than those for HNSCC; however, prospective data is paramount to verify these results before strong conclusions can be made.

Background: Early identification of small choroidal melanomas is important, as metastatic risk increases with tumor size. However, distinguishing small melanomas from benign choroidal nevi is challenging and may lead to unnecessary referrals and overtreatment. Both the MOLES scoring system and the deep learning algorithm MelAInoma have been developed to support assessment of pigmented choroidal lesions in non-expert settings. This study aims to compare the association between MOLES and MelAInoma scores and to assess their relative association with expert melanoma versus nevus diagnosis. Methods: In this retrospective cohort study, 86 patients with small pigmented choroidal lesions (29 melanomas and 57 nevi) diagnosed at a national ocular oncology referral center were included. MOLES scores were assigned by ocular oncologists based on multimodal examination, whereas MelAInoma scores were generated solely from color fundus photographs. Associations between scores were assessed using linear regression and the Jonckheere-Terpstra test. Univariable and multivariable binary logistic regression was used to evaluate associations with melanoma diagnosis. Results: MelAInoma scores increased monotonically with higher MOLES categories (p = 0.0001). Linear regression showed a statistically significant association between MOLES and MelAInoma scores, but with substantial dispersion (R² = 0.16). In univariable logistic regression, both MOLES and MelAInoma scores were associated with increased odds of melanoma diagnosis. MelAInoma showed a stronger association with diagnosis than MOLES (R² = 0.38 vs. 0.27). In multivariable analysis including both scores, each remained independently associated with melanoma diagnosis. Conclusions: Both MOLES and MelAInoma are effective for differentiating small choroidal melanomas from nevi. Although the scores are statistically associated, they capture partly distinct information. MelAInoma demonstrates slightly stronger association with melanoma diagnosis and provides fully reproducible output, supporting its role as a complementary aid in lesion triage.

Introduction: Neoadjuvant systemic and immunotherapy strategies in non-metastatic colon cancer have demonstrated high pathological response rates, raising interest in surgery-sparing approaches. Circulating tumour DNA (ctDNA) is an emerging biomarker for treatment response and minimal residual disease, but its role in guiding surgical omission in colon cancer remains unclear. This systematic review evaluates the diagnostic and prognostic accuracy of ctDNA in predicting pathological response following neoadjuvant therapy in non-metastatic colon cancer.

Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Embase/MEDLINE, Scopus, and the Cochrane Register were searched from inception to 21 October 2025. Eligible studies included adults with non-metastatic colon cancer treated with neoadjuvant therapy who had serial ctDNA assessment prior to surgery.

Results: Three cohort studies comprising 100 patients met inclusion criteria. Baseline ctDNA detection ranged from 42% to 84%. Across studies, ctDNA clearance following neoadjuvant therapy was consistently associated with major pathological response or pathological complete response, whereas persistent ctDNA strongly predicted residual viable tumour at resection. In the largest prospective cohort, 5 of 26 patients (19%) achieved ctDNA clearance prior to surgery; all were pathological responders, while 19 of 26 patients (73%) with persistent ctDNA demonstrated no pathological response. No study reported pathological complete response in the presence of persistently positive ctDNA. No prospective trial formally evaluated ctDNA-guided surgical omission.

Conclusions: Current evidence does not support the use of ctDNA alone to guide omission of surgery after neoadjuvant therapy in non-metastatic colon cancer-even in patients who show complete pathological response. While persistent ctDNA reliably identifies patients with residual disease, ctDNA clearance lacks sufficient positive predictive value to safely forego surgery. Prospective trials with standardised ctDNA platforms and predefined non-operative management protocols are required before ctDNA-guided organ preservation can be recommended.

Background: Erectile dysfunction is a common late effect of prostate radiotherapy. Hydrogel spacers aim to reduce radiation exposure to nearby structures by increasing the distance between the prostate and surrounding tissues, potentially preserving sexual function. Methods: In this retrospective cohort study of 117 prostate cancer patients who received hydrogel spacers, we compared pre- and post-insertion radiation dose and anatomical positioning of erectile structures using paired t-tests. Longitudinal sexual function, assessed via EPIC scores, was modeled using linear mixed-effects regression with natural splines (df = 3), incorporating random intercepts and slopes to account for within-subject variability. Results: Spacer insertion significantly reduced radiation dose to the left and right neurovascular bundles (mean reductions: 1.66 Gy, 95% CI: 1.32-2.00; and 1.64 Gy, 95% CI: 1.28-2.01, respectively; p < 0.01) and the right perineal artery (1.33 Gy, 95% CI: 0.57-2.09; p < 0.01). No significant dose changes were observed for the penile bulb or left perineal artery, nor in anatomical distances. However, spatial displacement was confirmed by significant overlap and integrated volume changes. Longitudinal modeling showed a significant decline in sexual function between 12 and ≥36 months post-treatment (Spline 2: β = -12.72, 95% CI: -18.52--6.92 and Spline 3: β = -6.68, 95% CI: -10.96--2.40; p < 0.01). Conclusions: Hydrogel spacer insertion was associated with significant reductions in radiation dose to erectile structures, most notably the neurovascular bundles and the right perineal artery. However, longitudinal analyses revealed no corresponding preservation of sexual function. These findings suggest that while hydrogel spacers effectively reduce radiation exposure to key anatomical structures, their clinical benefit for maintaining erectile function remains uncertain.

Background/objectives: SETD2 is a dual-function methyltransferase important for methylation of histone H3 at lysine 36 and α-tubulin in spindle microtubules. Genetic inactivation of SETD2 during oncogenesis drives loss of H3K36me3, genomic instability, and cancer progression. This study asked if disruption of genomic stability was a canonical feature of SETD2 inactivation via different pathways.

Methods: We evaluated the impact of EPZ-719, a pharmacologic SETD2 inhibitor, and an H3.3K36M mutant histone ("oncohistone") that binds and sequesters SETD2, on methylation activity and genomic stability in human cell lines. SETD2 activity was measured using in vitro methylation assays, H3K36me3 loss confirmed by Western analysis, and mitotic defects, specifically micronuclei and chromatin bridges, quantified with cytogenetic analysis.

Results: EPZ-719 caused a dose- and time-dependent reduction in SETD2 activity on both histone and tubulin substrates, accompanied by significant increases in chromatin bridges and micronuclei in retinal pigmented epithelial (RPE-1) and 786-O ccRCC cells. Similarly, oncohistone expression markedly decreased SETD2 function, as determined by H3K36me3 levels, and induced comparable mitotic defects in 786-O cells, and aneuploidy in two chondrocyte cell lines expressing the H3.3K36M oncohistone. Combining EPZ-719 with H3.3K36M expression did not exacerbate mitotic defects beyond either oncohistone or pharmacologic inhibition alone, consistent with inhibition of SETD2 as their shared underlying mechanism of action.

Conclusions: Pharmacologic inhibition and oncohistone-mediated sequestration of SETD2 converge on the induction of mitotic defects, underscoring SETD2's essential role in maintaining genomic stability. Identification of loss of genomic stability as a canonical feature of SETD2 inactivation points to a potential therapeutic liability associated with targeting SETD2 in cancers where it is overexpressed and reveals a mechanism that could contribute to the progression of cancers expressing oncohistone mutations.

We gratefully thank R [...].

Background: With an ongoing debate concerning the optimal timing of advanced ovarian cancer surgical treatment, primary debulking surgery (PDS) versus neoadjuvant chemotherapy followed by interval debulking surgery (IDS), this study aimed to compare survival outcomes between PDS and IDS populations and evaluate prognostic factors in a real-world cohort of patients treated with first-line chemotherapy and bevacizumab.

Methods: A retrospective multi-center study was conducted involving 369 patients with newly diagnosed advanced ovarian cancer. Patient data included demographics, histology, treatment details, chemotherapy response, and survival outcomes. Kaplan-Meier estimates with log-rank tests were used for univariate analyses, as well as Cox proportional hazard models for multivariate analyses.

Results: Patients undergoing IDS were older (62.5 vs. 60.0 years), had higher pretreatment CA-125 (1846 vs. 395.6 IU/mL), an increased proportion were at with stage IV (36.25% vs. 21.10%), and they received fewer bevacizumab cycles (12 vs. 18) compared to those undergoing PDS. Median progression-free survival (PFS) was 18.6 months (95% CI: 17.3-20.2) and overall survival (OS) was 45.4 months (95% CI: 41.1-52.1). Multivariate analysis confirmed poor chemotherapy response (HR 1.80, 95% CI: 1.36-2.37; p < 0.0001) and IDS (HR 1.65, 95% CI: 1.37-2.39; p < 0.0001) as independent predictors of shorter PFS. For OS, independent risk factors were age > 70 (HR 1.62; p = 0.0202), poor response (HR 2.03; p < 0.0001), and IDS (HR 1.75; p = 0.0006).

Conclusions: In this real-world cohort treated with first-line chemotherapy and bevacizumab, interval debulking surgery was associated with inferior progression-free and overall survival compared with primary debulking surgery. However, these findings reflect a high-risk population and are strongly influenced by patient selection and treatment pathways, underscoring the need for cautious interpretation.

Background: Robotic-assisted partial nephrectomy (RAPN) is widely used for nephron-sparing surgery. Vessel sealing technologies play a crucial role in these procedures, influencing ischemia time, blood loss, and surgical outcomes. This study compares the efficacy and safety of using a robotic vessel sealer (VS) versus conventional bipolar energy in robotic partial nephrectomy.

Methods: A retrospective analysis was conducted on patients (n = 112) undergoing RAPN using either a robotic VS or bipolar energy grasper between 2023 and 2025. Parameters analyzed included ischemia time, estimated blood loss (EBL), postoperative complications, and functional outcomes. Statistical comparisons were performed to assess differences in perioperative and postoperative metrics.

Results: The vessel sealer (VS) group (n = 54) had significantly lower blood loss (40 mL vs. 132.5 mL, p = 0.037) than the bipolar group (n = 58). Ischemia time was similar (24.5 min vs. 20.46 min, p = 0.444). No significant differences were found in operative time, console time, docking time, or postoperative complications (p > 0.05). The tumor diameter (CT: 28.38 mm vs. 25.5 mm, p = 0.655; pathology: 2.34 cm vs. 1.96 cm, p = 0.375) and Radius-Exophytic/Endophytic-Nearness to collecting system or sinus-Anterior/posterior-Location relative to polar lines (RENAL) score (7.00 vs. 6.17, p = 0.202) were slightly higher in the bipolar group but not statistically significant.

Conclusions: Both techniques seem to be used for tumors of comparable size and complexity, suggesting no strong selection bias. Future research should prioritize randomized controlled trials assessing long-term renal function, cost-effectiveness, and potential refinements of robotic vessel sealing technology. A broader, multicenter analysis could provide further insight into optimal device selection for robotic partial nephrectomy.

Background/objectives: To systematically review and critically appraise AI methods for RECIST-based radiologic treatment response assessment in solid tumors, comparing image-derived and report-derived approaches and summarizing their performance, agreement with reference standards, and validation quality.

Methods: This systematic review followed PRISMA guidelines. We searched Embase, MEDLINE, Web of Science, Scopus, and the Cochrane Library on 6 December 2025. We included English-language original studies (2015-2025) in solid tumors where AI directly assigned RECIST response categories and was validated against a reference standard; studies without RECIST-based response endpoints or non-solid tumor populations were excluded. We distinguished image-based techniques that assign RECIST categories from direct analysis of imaging data from report-based techniques that infer RECIST categories from radiology reports using natural language processing.

Results: Evidence remains sparse; we identified four eligible studies (two image-based and two report-based). DeepSeek-V3-0324 and GatorTron, both report-based approaches, achieved high accuracy (96.5% and 89%, respectively) in treatment response evaluation, with DeepSeek demonstrating higher expert agreement (κ 0.85-0.90). The nnU-Net and 3D U-Net pipelines, both image-based, showed high segmentation performance (DSC 0.85, VS 0.89) and treatment response classification accuracy of 0.77 for R1, with moderate agreement with the manual reference (κ = 0.60); nnU-Net also achieved moderate to almost perfect agreement (Cohen's κ 0.67-0.81) in RECIST 1.1 measurements.

Conclusions: AI-based RECIST-oriented response assessment is feasible and potentially beneficial for standardization, efficiency, and scalability, but current evidence is limited and heterogeneous, requiring larger multi-center studies with rigorous external validation before clinical adoption. Key limitations include data source variability, reference standard inconsistencies, and lack of robust external validation.