Cancer[JOURNAL]
Sun
200 papers
A weakly supervised deep learning-based recurrence prediction and risk stratification of lung adenocarcinoma from pathology whole-slide images.
Xue B, Liu Y, Cai M … +7 more , Gu L, Bai J, Yao L, Li J, Wang L, Huang X, Yao D
BMC Cancer · 2026 Jun · PMID 42286527 · Full text
BACKGROUND: Accurate prediction of postoperative recurrence in lung adenocarcinoma (LUAD) is essential for guiding clinical decision-making and improving patient outcomes. Although various predictive models have been dev...
BACKGROUND: Accurate prediction of postoperative recurrence in lung adenocarcinoma (LUAD) is essential for guiding clinical decision-making and improving patient outcomes. Although various predictive models have been developed, most rely on complex genomic analyses and high-dimensional clinical data. The complexity of these approaches substantially limits their feasibility for routine clinical use. To address this clinical challenge, this study aims to predict postoperative recurrence using routinely available hematoxylin and eosin (H&E)-stained images and characterize the associated biological features. METHODS: A total of 329 patients who underwent curative resection at the First Affiliated Hospital of Wenzhou Medical University (FHWMU) were retrospectively enrolled and randomly assigned to training and internal validation cohorts in a 7:3 ratio. An independent external validation cohort comprising 70 patients from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) was included. Three patch-level feature extractors (Inception_V3, ResNet18, and DenseNet121) were evaluated within a weakly supervised multiple-instance learning (MIL) framework incorporating automated region-of-interest (ROI) detection on segmented whole-slide images (WSIs). Model performance was assessed using the area under the receiver operating characteristic curve (AUC), Kaplan-Meier (KM) survival analysis, and multivariable Cox proportional hazards regression. Transcriptomic profiling and gene set enrichment analysis (GSEA) were conducted to investigate biological differences between risk groups. RESULTS: The model achieved AUCs of 0.923 in the training cohort, 0.891 in the internal validation cohort, and 0.847 in the external validation cohort. The model effectively stratified patients into high- and low-risk groups with significantly different recurrence-free survival (RFS) across all cohorts (all P < 0.001) and retained prognostic value within AJCC stages I-III. Transcriptomic analyses revealed consistent enrichment of cell cycle-related pathways and neutrophil extracellular trap (NET) formation in high-risk patients across both institutional and CPTAC cohorts, aligning with distinct biological profiles of the model-derived risk stratification. CONCLUSIONS: This weakly supervised deep learning framework enables accurate and externally validated prediction of postoperative recurrence in LUAD using routinely available histopathological images, and integration of histopathological features with molecular analyses enhances biological interpretability. This work provides a clinically accessible and cost-effective tool for postoperative risk assessment in LUAD patients.
Factors associated with readmission following reconstruction in head and neck skin cancer: a national readmission database analysis.
Wu CY, Chung MH
BMC Cancer · 2026 Jun · PMID 42286515 · Full text
BACKGROUND: Readmission following reconstructive surgery for head and neck skin cancer is associated with increased morbidity and healthcare costs. However, risk factors in this population are poorly defined. This study...
BACKGROUND: Readmission following reconstructive surgery for head and neck skin cancer is associated with increased morbidity and healthcare costs. However, risk factors in this population are poorly defined. This study aimed to evaluate the incidence, causes, and predictors of 90-day unplanned readmission following reconstructive surgery for head and neck skin cancer. METHODS: This retrospective study included adults with head and neck skin cancer who underwent reconstruction between January and September 2016-2020, extracting data from the National Readmission Database. Patients who died during the index admission or had missing key information were excluded. The primary outcome was 90-day unplanned readmission. Independent predictors were identified using logistic regression analysis. Postoperative acute kidney injury (AKI), identified using International Classification of Disease (ICD) diagnosis codes, was evaluated as a secondary outcome. RESULTS: In total, 5,243 patients (mean age 72 years, 78% male) were included, representing 9,490 hospitalizations nationwide. Overall, 1,046 patients (20.0%) experienced 90-day readmission. Private or HMO insurance was associated with lower odds of readmission (aOR = 0.72, 95% CI: 0.57-0.91). Severe liver disease (aOR = 4.69, 95% CI: 1.65-13.33), sepsis (aOR = 1.93, 95% CI: 1.22-3.08), dysphagia (aOR = 1.70, 95% CI: 1.20-2.41), renal disease (aOR = 1.41, 95% CI: 1.17-1.70), and bleeding/hemorrhage (aOR = 1.44, 95% CI: 1.11-1.88) were significant factors associated with readmission. AKI occurred in 306 patients (5.8%). CONCLUSIONS: This study identified severe liver disease, sepsis, dysphagia, and renal disease as factors independently associated with increased 90-day readmission risk. AKI was not uncommon, underscoring the importance of perioperative optimization and vigilant monitoring in high-risk patients.
AACR 2026.
Senft D
Nat Rev Cancer · 2026 Jul · PMID 42286258 · Publisher ↗
Abstract loading — click title to view on PubMed.
Alcohol consumers' receptivity to artificial intelligence-generated alcohol-cancer risk messages: An experimental study.
Asfar T, Brown EC, Penedo FJ … +7 more , Abrams I, Jayakumaran J, Oluwole OJ, Ferdous T, Naimi T, Avendano D, Maziak W
Cancer · 2026 Jun · PMID 42283352 · Full text
BACKGROUND: Alcohol is a group 1 carcinogen linked to seven cancers, yet awareness of this risk remains low in the United State. Identifying effective alcohol-cancer communication strategies is a public health priority....
BACKGROUND: Alcohol is a group 1 carcinogen linked to seven cancers, yet awareness of this risk remains low in the United State. Identifying effective alcohol-cancer communication strategies is a public health priority. The objective of this study was to test the effects of message specificity (general vs. cancer-specific) and visual intensity (text-only, neutral pictorial, graphic pictorial) on message receptivity (attention, emotional reactions) and precursors of behavior (harm perception; intentions to reduce, limit, or stop drinking) among moderate and heavy alcohol consumers. METHODS: Eight evidence-based text messages were created across two topics: general and cancer-specific harm. Artificial intelligence was used to generate pictorial versions at two intensities: neutral (symbolic, no visible disease) and graphic (explicit health consequences). In a 2025 online within-subject/between-subject crossover experiment, 639 US adult consumers (aged 21 years and older; 49.3% female) each viewed two randomly selected messages (one general, one cancer-specific) presented in three formats (text-only, neutral, and graphic; for six total formats), with counterbalanced order. Linear mixed-effects models were used to estimate differences by intensity, specificity, and drinking levels, reporting regression coefficients (β, 95% confidence intervals). RESULTS: Cancer-specific messages produced greater attention, emotional reactions, and intentions to reduce drinking than general messages (β = 0.10-0.19; p < .05). Graphic pictorials outperformed neutral images on emotional and behavioral outcomes (β = 0.19-0.22; p < .05). Moderate consumers showed stronger perceived harm and message responsiveness than heavy consumers (β = 0.29-0.77; p < .05). CONCLUSIONS: Artificial intelligence-generated alcohol-cancer messages are feasible and effective in strengthening precursors to behavior change. Cancer-specific content and higher visual intensity enhance impact, particularly among moderate consumers, highlighting the importance of tailoring alcohol-cancer communication strategies to different audience characteristics.
Ultrasound-based predictive models for response to neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis.
Yi C, Xu T, You R … +3 more , Zhang Q, Liu R, Yang X
BMC Cancer · 2026 Jun · PMID 42277767 · Full text
OBJECTIVE: This meta-analysis aimed to assess the diagnostic efficacy of ultrasound-based prediction models in evaluating the response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: A systematic re...
OBJECTIVE: This meta-analysis aimed to assess the diagnostic efficacy of ultrasound-based prediction models in evaluating the response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: A systematic review was conducted using PubMed, Embase, and Web of Science from inception to May 2025. We focused on studies evaluating ultrasound-based prediction models for NAC response in breast cancer. Two investigators independently performed study selection and data extraction according to predefined eligibility criteria. The risk of bias was assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Meta-analysis was performed using Stata 14.0 software, with the area under the curve (AUC) and its 95% confidence interval (CI) as the primary measure of diagnostic accuracy. RESULTS: Fourteen retrospective studies with a total of 35 prediction models were included. PROBAST assessment indicated a high overall risk of bias in most studies (10 out of 14). The pooled AUC for all ultrasound-based prediction models in predicting NAC response was 0.84 (95% CI: 0.82, 0.86). However, substantial heterogeneity was observed among the studies (I = 69.7%, p < 0.001). Subgroup analyses suggested that model features and the prediction outcomes were major sources of heterogeneity. In the test cohort, the model combining ultrasound with clinical features demonstrated the best performance in predicting pathologic complete response (pCR), with a pooled AUC of 0.88 (95% CI: 0.84-0.92) and no heterogeneity (I = 0.0%). Sensitivity analyses confirmed the robustness of the findings. Although the funnel plot appeared symmetrical, both Begg's and Egger's tests indicated publication bias (p < 0.01). Notably, 10 of 14 included studies (71.4%) were at high overall risk of bias, and all studies were single-center and conducted in China, which substantially limits the immediate clinical translation of these findings. CONCLUSION: Ultrasound-based prediction models show encouraging discriminative ability for predicting pCR (pooled AUC 0.84, 95% CI 0.82-0.86), suggesting preliminary potential. However, given the high risk of bias, substantial heterogeneity, and geographic limitation (all studies from China), the current evidence should be considered exploratory and hypothesis-generating rather than practice-changing. Future prospective, multicenter, and rigorously designed studies are needed to confirm these findings.
Fusion of MRI-radiomics and clinical features to improve pathological T-stage prediction of rectal cancer: a multicenter study.
Zhu H, Sun J, Li X … +4 more , Nie S, Gong J, Tong T, Li X
BMC Cancer · 2026 Jun · PMID 42277750 · Full text
BACKGROUND: Developing a rational model for precise preoperative staging of rectal cancer using magnetic resonance imaging is crucial for improving the therapeutic effect and prognosis of patients. To investigate the fea...
BACKGROUND: Developing a rational model for precise preoperative staging of rectal cancer using magnetic resonance imaging is crucial for improving the therapeutic effect and prognosis of patients. To investigate the feasibility and efficacy of a T2-weighted imaging (T2WI) based radiomics model combined with clinical features for preoperative T1-2/T3 staging prediction in rectal cancer. METHODS: A total of 968 rectal adenocarcinoma patients (T1-2 stage, n = 562; T3 stage, n = 406) were retrospectively enrolled in this study. We randomly divided it into a training cohort (n = 774) and an internal validation cohort (n = 194). Additional 82 patients from another center used as an independent external validation cohort. For each patient, 1210 radiomics features were extracted from T2WI images. Least absolute shrinkage and selection operator were applied for feature selection. Support vector machine classifier was used to develop the radiomics model. Six clinical features were collected and selected to build the clinical model using the recursive feature elimination algorithm. A weighted fusion method was applied to combine the radiomics with clinical model to develop the fusion model. The performances of the above three models were evaluated using ROC, calibration, and decision curves. RESULTS: The radiomics and clinical model yielded AUC of 0.858 (95% CI, 0.801-0.904) and 0.780 (95% CI, 0.715-0.836) in internal validation cohort, while the fusion model generated higher performance with AUC of 0.875 (95% CI, 0.820-0.918). The external validation cohort further validated the effectiveness of the fusion model with AUC of 0.828 (95% CI, 0.729-0.903). The calibration and decision curves confirmed that the fusion model was well calibrated and had clinical utility. CONCLUSIONS: Combined T2WI radiomics features and clinical features modeling can effectively predict T-stage (T1-2/T3) of rectal cancer and provide valuable reference for clinical decision making.
Genome-wide association study of never-smoking non-drinking young adults developing oral squamous cell carcinoma.
Cardin GB, Pellerin-Viger A, Bernard M … +13 more , Kessai F, Ayad T, Bissada E, Guertin L, Tabet P, Gologan OE, Filion E, Nguyen-Tan PF, Desilets A, Cheng AP, Rodier F, Bahig H, Christopoulos A
BMC Cancer · 2026 Jun · PMID 42277742 · Full text
BACKGROUND: Germline risk variants for oral squamous cell carcinoma (OSCC) in never-smoking non-drinking (NSND) young adults (YA) are poorly characterized and genome-wide association studies focusing on NSND YA OSCC are...
BACKGROUND: Germline risk variants for oral squamous cell carcinoma (OSCC) in never-smoking non-drinking (NSND) young adults (YA) are poorly characterized and genome-wide association studies focusing on NSND YA OSCC are lacking. This study aims to evaluate if rare germline variants are associated with NSND YA OSCC. METHODS: We conducted a retrospective, single-center Canadian cohort study of patients who underwent primary surgery for OSCC between 2010 and 2024. Genome-wide association analyses were performed for three comparisons: 1- NSND YA (n = 10) vs. other OSCC (n = 150), 2- all-ages NSND (n = 29) vs. ever-smoker and/or drinker (n = 131), and 3- any risk factor YA OSCC (n = 22) vs. age ≥ 45 (n = 138). A polygenic risk score for age at OSCC diagnosis was derived from clumping + thresholding. RESULTS: We included 160 patients of European ancestry with a diagnosis of OSCC: 22 YA and 29 NSND patients; 10 patients were both YA and NSND. YA cases predominantly involved the oral tongue. One rare variant, rs191595756, showed a suggestive association with NSND YA OSCC (p = 3.3e-06), but did not reach genome-wide significance. This variant is located in an intron of LINC00944 and in an exon of LINC02824. No rare variant signals were supported in the all-ages NSND and any risk factor YA OSCC. None of the identified variants is reported in ClinVar. An exploratory polygenic risk score composed of 13 index variants was constructed. It is independent of NSND or ever-smoker and/or drinker status. It is also independent of oral tongue or other oral cavity primary cancer site. CONCLUSIONS: This is the first study investigating genome-wide associations in NSND YA OSCC. No single germline variant of genome-wide significance associated with NSND YA OSCC occurrence was found, suggesting a polygenic architecture. Larger, multicentric studies are needed to validate a polygenic risk score specifically predictive of NSND YA OSCC risk.
Clinical factors are more strongly associated with prognosis than genetic alterations in early-onset colorectal cancer: a retrospective cohort study.
Le KT, Tran HD, Do MD … +3 more , Nguyen TH, Nguyen TT, Tran TT
BMC Cancer · 2026 Jun · PMID 42277735 · Full text
BACKGROUND: Early-onset colorectal cancer (EOCRC) is increasing globally and exhibits both aggressive clinicopathological features and distinct molecular characteristics. However, the relative contribution of clinical an...
BACKGROUND: Early-onset colorectal cancer (EOCRC) is increasing globally and exhibits both aggressive clinicopathological features and distinct molecular characteristics. However, the relative contribution of clinical and genetic factors to prognosis remains unclear, particularly in underrepresented populations. METHODS: A retrospective cohort study was conducted on 100 colorectal cancer (CRC) patients under 50 years of age, diagnosed and treated between January 2016 and December 2020, with follow-up up to 60 months or until death. Patients were stratified by patient characteristics, oncological features, and genetic mutation status to perform overall survival (OS) analysis. RESULTS: The mean OS was 49.8 months (95% CI: 46.4-53.2), with an estimated 5-year OS rate of 65.2%. The mean disease-free survival (DFS) was 50.1 months (95% CI: 46.2-53.9). In univariate analysis, factors significantly associated with OS included serum CEA level at diagnosis (p = 0.001), histological grade (p = 0.006), mode of surgery (emergency vs. elective) (p = 0.003), curative resection status (p < 0.001), disease stage (p < 0.001), mutations in the POL-MMR DNA repair gene group (p = 0.035), high mutation accumulation (p = 0.020), PIK3CA mutation (p = 0.036), and co-mutation of RAS/RAF and MMR genes (p = 0.011). However, when adjusted for disease stage, only patient and oncological factors remained associated with OS, including elevated CEA (HR = 2.33, 95% CI: 1.2-4.7, p = 0.018), poorly differentiated tumors (HR = 2.57, 95% CI: 1.2-5.7, p = 0.021), emergency surgery (HR = 3.50, 95% CI: 1.5-7.9, p = 0.003), and curative treatment (HR = 0.10, 95% CI: 0.05-0.2, p < 0.001). CONCLUSION: In EOCRC, clinical and treatment-related factors remained independently associated with overall survival after adjustment for disease stage, whereas the evaluated genetic variables did not retain statistical significance. These findings highlight the importance of clinical management strategies, while the prognostic value of genetic alterations requires further investigation.
Granzyme B, HIF-1α, VEGFA and SerpinB9 in the local tumour immune system of immune-stimulated slice cultures of head and neck cancer.
Greier MDC, Dudas J, Federspiel J … +3 more , Ferro F, Bergher P, Hofauer BG
BMC Cancer · 2026 Jun · PMID 42277718 · Full text
BACKGROUND: Even when T-cell activation is successful, head and neck squamous cell carcinoma (HNSCC) often becomes resistant to immunotherapy. This study investigated the molecular factors that influence immune-induced t...
BACKGROUND: Even when T-cell activation is successful, head and neck squamous cell carcinoma (HNSCC) often becomes resistant to immunotherapy. This study investigated the molecular factors that influence immune-induced tumour cell death in organotypic HNSCC slice cultures (SCs). METHODS: SC samples were obtained from 23 patients (22 with HNSCC and one tumour-free control). Immune stimulation was performed using a T-cell activator kit. The protein levels of granzyme B (GrB), cleaved caspase-3 (CC3), Slug, hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor alpha (VEGFA) and SerpinB9 were assessed using immunohistochemistry (IHC) and immunofluorescence (IF). The patient samples were stratified according to Slug expression and HPV status. Slug, VEGFA, HIF-1α, HPV positivity and baseline SerpinB9 were considered input determinants, whereas GrB, CC3 and induced SerpinB9 were considered response factors. RESULTS: The baseline intensity of HIF-1α was low in most tumour tissue samples, except in two patients who had high levels. SerpinB9 levels were higher in tumour cells from five patients than in a single tumour-free control sample. VEGFA immunofluorescence (IF) levels were clearly higher in several tumour samples, including HPV-positive cases, compared to the single tumour-free control sample. A significant correlation was observed between HIF-1α and VEGFA IF sum intensities. Following immune stimulation, the intensity of GrB increased in 14 out of 22 tumour samples. CC3 was induced in tumour cells in 12 out of 19 samples, particularly in five out of six HPV-positive samples, while SerpinB9 was induced in nine out of 18 samples. Interestingly, this occurred in only two out of six HPV-positive samples. The induction of CC3 and SerpinB9 was significantly correlated (r = 0.67, p < 0.01). No difference in GrB induction was observed between Slug-positive and Slug-negative tumours. However, lower levels of CC3 and SerpinB9 induction were observed in Slug-positive tumours. CONCLUSIONS: The Slug-HIF-1α-VEGFA axis may enable tumour cells to evade the primary immune response by inhibiting apoptosis induced by the immune system. Extensive immune activation induced both the caspase cascade and the protective factor SerpinB9 in tumour cells of HPV-negative HNSCC mainly. GrB, CC3 and SerpinB9 exhibited reduced spatial gradients at increasing distances from the immune-stimulating beads.
Impact of time to ablation on survival outcomes in patients with colorectal liver metastases: an inverse probability-weighted cohort study.
Yue X, Kong Y, Huang X … +3 more , Tang F, Cao X, Zhou X
BMC Cancer · 2026 Jun · PMID 42277707 · Full text
BACKGROUND: The optimal timing for thermal ablation (TA) in patients with colorectal liver metastases (CRLM) eligible for local curative therapy remains undefined. This study aimed to evaluate the impact of time to ablat...
BACKGROUND: The optimal timing for thermal ablation (TA) in patients with colorectal liver metastases (CRLM) eligible for local curative therapy remains undefined. This study aimed to evaluate the impact of time to ablation (TTA) on long-term survival outcomes. METHODS: We retrospectively analyzed 220 patients with ablatable CRLM (≤ 5 liver metastases, maximum diameter ≤ 3 cm) who underwent TA between January 2015 and December 2022. Based on the TTA, patients were stratified into three groups: upfront TA (UTA, ≤ 3 months, n = 113), short-term delayed TA (DTA, 3-6 months, n = 59), and long‑term DTA (> 6 months, n = 48). Inverse probability of treatment weighting (IPTW) was applied to reduce baseline selection bias. The primary endpoint was progression‑free survival (PFS), and the secondary endpoint was overall survival (OS). RESULTS: After IPTW adjustment, the difference in PFS among the three groups was statistically significant (P = 0.012). The 1‑, 3‑, and 5‑year PFS rates were 61.5%, 31.2%, and 30.2% in the UTA; 47.7%, 15.9%, and 4.7% in the short‑term DTA; and 53.4%, 8.5%, and 3.1% in the long‑term DTA. Multivariable Cox regression identified both short-term DTA and long‑term DTA as an independent risk factor for worse PFS (HR = 1.80. 95% CI: 1.20-2.70, PP = 0.005); and HR = 1.99, 95% CI: 1.20-3.31, P = 0.008). No significant difference in OS was observed among the three groups. Subgroup analyses showed that DTA was associated with poorer PFS than UTA in patients with CEA > 5 ng/mL, synchronous metastases, N1-2 stage, or lymphovascular invasion. Moreover, among patients receiving UTA, adding neoadjuvant chemotherapy did not provide additional PFS or OS benefit compared with ablation alone (P > 0.05). CONCLUSION: In patients with ablatable CRLM, UTA significantly improves PFS compared with DTA, and DTA is an independent risk factor for worse PFS. Therefore, for eligible patients, UTA is recommended in preference to prolonged systemic therapy.
Characteristics and hematological indicators predictors of immunotherapy response in advanced non-small cell lung cancer.
Zhao N, Wu X, Zhao W … +3 more , Cheng X, He H, Cao D
BMC Cancer · 2026 Jun · PMID 42277693 · Full text
OBJECTIVE: Immune checkpoint inhibitors (ICIs) have significantly improved the treatment outcomes for advanced non-small cell lung cancer (NSCLC), but patient benefits vary individually. Therefore, identifying biomarkers...
OBJECTIVE: Immune checkpoint inhibitors (ICIs) have significantly improved the treatment outcomes for advanced non-small cell lung cancer (NSCLC), but patient benefits vary individually. Therefore, identifying biomarkers to predict the efficacy and prognosis of immunotherapy is crucial. Hematological markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin-bilirubin (ALBI) score, and lactate dehydrogenase (LDH) levels may correlate with tumor prognosis. This study aimed to evaluate the prognostic value of these hematological and clinical markers in advanced NSCLC patients treated with ICIs, providing a basis for individualized treatment strategies. METHODS: This retrospective study included NSCLC patients treated with ICIs at the Tumor Centers of Renmin Hospital of Wuhan University and Macheng City People's Hospital between January 2021 and December 2023. Clinical data such as gender, age, ECOG PS score, clinical stage, and treatment details were collected. Patients were stratified based on NLR, PLR, LDH, and ALBI scores. ROC curve analysis assessed the predictive capacity of these markers for mortality risk. Chi-square tests, logistic regression, Kaplan-Meier survival analysis, and log-rank tests were used to analyze short-term efficacy, immune-related adverse events (irAEs), progression-free survival (PFS), and overall survival (OS). Cox regression identified independent prognostic factors for PFS and OS. RESULTS: A total of 198 advanced NSCLC patients (median follow-up: 28.1 months) were included. Median PFS (mPFS) and OS (mOS) were 7.7 months (95% CI: 6.9 ~ 8.5) and 20.1 months (95% CI: 18.2 ~ 21.9), respectively. ROC analysis demonstrated significant predictive value for baseline NLR, PLR, ALBI, and LDH in mortality risk (AUC: 0.804, 0.694, 0.684, 0.726, respectively). Efficacy analysis revealed PD-L1 positivity (OR = 0.361, 95% CI: 0.161 ~ 0.808, P = 0.013) and ALBI < -2.68 (OR = 2.524, 95% CI: 1.148-5.552, P = 0.021) as independent predictors of objective response rate (ORR: 25.8%), while camrelizumab significantly reduced response rates (OR = 0.157, P = 0.006). Baseline NLR, PLR, ALBI, and LDH significantly stratified PFS (P < 0.05): low NLR (8.7 vs. 7.1 months, P = 0.001), low PLR (7.9 vs. 7.4 months, P = 0.007), low ALBI (8.1 vs. 7.0 months, P = 0.028), and low LDH (9.5 vs. 7.1 months; 46.3% risk reduction, P < 0.001). In the adenocarcinoma subgroup, LDH remained an independent prognostic factor (9.5 vs. 6.8 months, P = 0.032). For squamous cell carcinoma, low NLR (9.1 vs. 7.1 months, P = 0.002), low PLR (10.2 vs. 7.4 months, P = 0.002), low ALBI (8.7 vs. 7.1 months, P = 0.022), and low LDH (9.1 vs. 7.5 months, P = 0.002) were significant. Baseline markers also predicted OS: low NLR (21.4 vs. 17.5 months, P < 0.001), low PLR (20.4 vs. 17.7 months, P = 0.009), and low LDH (21.4 months; 42.5% risk reduction, P < 0.001). Subtype analysis showed adenocarcinoma benefited from low NLR (21.4 vs. 16.5 months, P = 0.013) and low LDH (20.1 vs. 17.5 months, P = 0.021), while squamous carcinoma relied on low NLR (21.4 vs. 16.8 months, P = 0.008), low PLR (21.8 vs. 20.1 months, P = 0.024), low ALBI (21.4 vs. 18.2 months, P = 0.047), and low LDH (24.6 vs. 19.8 months, P = 0.001). Multivariate Cox analysis identified radiotherapy, NLR, and LDH as independent predictors of PFS: Radiotherapy reduced risk by 37.5% (HR = 0.625, P = 0.004); NLR ≥ 3.72 (HR = 1.642) and LDH ≥ 226.5 U/L (HR = 1.821) increased risk by 64.2% and 82.1% (P < 0.05). For OS, adenocarcinoma (HR = 0.361) and squamous carcinoma (HR = 0.350) reduced mortality risk by 63.9% and 65.0% (P < 0.05), while NLR ≥ 3.72 (HR = 1.536), and LDH ≥ 226.5 U/L (HR = 1.728) increased risk by 53.6% and 72.8% (P < 0.05). LDH ≥ 226.5 U/L (HR = 2.372) stained highest risk in squamous carcinoma (P < 0.05). CONCLUSIONS: Baseline hematological markers (NLR, PLR, ALBI, LDH) are valuable predictors of efficacy and prognosis in advanced NSCLC patients undergoing immunotherapy. Their prognostic roles vary by pathological subtype: squamous carcinoma relies more on inflammatory markers, while adenocarcinoma emphasizes metabolic markers and genetic mutations. This study provides a hematological biomarker-based stratification framework for individualized immunotherapy decisions in advanced NSCLC, offering critical guidance for optimizing treatment and prognosis management.
Clinical analysis and prognostic factors in children with neuroblastoma-associated opsoclonus-myoclonus syndrome: a multicenter retrospective study.
Zheng C, Wan C, Wang J … +9 more , Wu Y, Cai W, Li T, Gao Q, Wang J, Zhang S, Yuan X, Zhang B, Hai B
BMC Cancer · 2026 Jun · PMID 42277674 · Full text
BACKGROUND: The long-term neurological outcomes for children diagnosed with neuroblastoma associated with Opsoclonus Myoclonus Syndrome (NB-OMS) are not well characterized, primarily due to the infrequency of the conditi...
BACKGROUND: The long-term neurological outcomes for children diagnosed with neuroblastoma associated with Opsoclonus Myoclonus Syndrome (NB-OMS) are not well characterized, primarily due to the infrequency of the condition. This multicenter study sought to evaluate the rate of neurological recovery and the long-term neurodevelopmental sequelae within this patient population. METHODS: A retrospective study at nine Chinese medical centers (January 2015 - January 2025) involved 39 children with NB-OMS. Researchers gathered data on demographics, clinical presentation, tumor traits, treatment, and outcomes. Non-parametric tests and multivariate logistic regression identified prognostic factors. RESULTS: In this study, a cohort of 39 patients was examined, with a median age at onset of 22 months. The retroperitoneum was identified as the most prevalent tumor location, accounting for 79.5% of cases. The majority of tumors were classified within the low-risk and intermediate risk, as determined by the International Neuroblastoma Risk Group Staging System, comprising 87.2% of the sample. Follow-up was conducted for 37 patients, all of whom exhibited symptom improvement, resulting in a 100% survival rate. Nonetheless, neurological sequelae were detected in 16 children (43.2%). A higher OMS severity score at onset demonstrated a strong trend towards significance (OR = 1.42, 95% CI: 1.00-2.01, P = 0.051). Multivariate analysis revealed that delayed initiation of treatment, defined as greater than 30 days, was a significant independent risk factor for the development of sequelae (Odds Ratio [OR] = 22.98, 95% Confidence Interval [CI]: 2.67-197.63, P = 0.004). Additionally, relapse of opsoclonus-myoclonus syndrome emerged as a significant independent risk factor (OR = 13.74, 95% CI: 1.37-137.34, P = 0.026). Furthermore, the use of combination immunotherapy, consisting of corticosteroids and intravenous immunoglobulin (IVIG), was associated with a significantly reduced median time to symptom resolution compared to non-combination therapy (5 months versus 8.5 months, P = 0.001). CONCLUSION: OMS is a chronic immune disorder often misdiagnosed, leading to treatment delays. Prompt first-line immunotherapy can quickly alleviate OMS symptoms. Early treatment and reducing relapses are crucial for better long-term outcomes. Future multicenter studies are needed to confirm the effectiveness of new immunotherapies.
Meeting the moment: Addressing racial disparities in cancer survival.
Barber LE, Collin LJ, Bailey ZD … +1 more , Ashad-Bishop KC
Cancer · 2026 Jun · PMID 42272428 · Publisher ↗
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Evaluation of cerebrospinal fluid human epididymis protein 4 for leptomeningeal metastasis in non-small cell lung cancer: a prospective cohort study.
Lin YJ, He MY, Xie Y … +3 more , Yin ZY, Lin XW, Hu LL
BMC Cancer · 2026 Jun · PMID 42271303 · Full text
BACKGROUND: Diagnosing and monitoring leptomeningeal metastasis (LM) presents a significant clinical challenge. This study evaluated cerebrospinal fluid (CSF) Human Epididymis Protein 4 (HE4) as a novel diagnostic and mo...
BACKGROUND: Diagnosing and monitoring leptomeningeal metastasis (LM) presents a significant clinical challenge. This study evaluated cerebrospinal fluid (CSF) Human Epididymis Protein 4 (HE4) as a novel diagnostic and monitoring biomarker for LM in non-small cell lung cancer (NSCLC). METHODS: A prospective cohort study enrolled 117 participants (including 61 NSCLC patients with LM and 56 controls without central nervous system malignancies) from March 2023 to December 2024. Paired CSF and serum levels of HE4, carcinoembryonic antigen (CEA), and Cytokeratin 19 Fragment (CYFRA21-1) were measured using electrochemiluminescence immunoassay. Multivariable binary logistic regression, adjusting for clinical covariates (KPS, ICP, and symptom-to-diagnosis interval), was employed to identify independent diagnostic predictors. Diagnostic performance was quantified using receiver operating characteristic (ROC) curve analysis and compared via the DeLong test. Serial CSF HE4 monitoring was performed in a subset of patients to assess treatment response. RESULTS: CSF HE4 levels were markedly elevated in LM patients compared to controls (median 807.00 vs. 99.35 pmol/L, P < 0.001). Multivariable logistic regression revealed that CSF HE4 was a robust, independent diagnostic factor for LM (Adjusted OR = 1.027; 95% CIs: 1.010-1.044; P = 0.001), along with the CSF-to-serum HE4 ratio (Q; P = 0.046). The multivariable model demonstrated excellent calibration (Hosmer-Lemeshow test, P = 0.366). In ROC analysis, CSF HE4 (AUC = 0.895) significantly outperformed Q (AUC = 0.769), CSF CEA (AUC = 0.701), and CSF CYFRA21-1 (AUC = 0.664) (all P < 0.05). At an optimal cutoff of 173.00 pmol/L, CSF HE4 yielded a sensitivity of 83.21% and specificity of 92.86%. Subgroup analysis indicated higher CSF HE4 in cytology-positive and progressive disease patients. Longitudinal monitoring showed that dynamic fluctuations in CSF HE4 closely mirrored clinical treatment response and disease progression. CONCLUSION: CSF HE4 is a promising biomarker for the diagnosis of NSCLC related LM. For CSF HE4, its robust diagnostic performance and correlation with disease activity support its use for both initial diagnosis and therapeutic monitoring.
Clinical benefit of various HER2-directed regimens in gastrointestinal malignancies: a retrospective cohort study.
Khanna V, Vadde S, Henry AS … +8 more , Johnson TP, Shaheen S, Heestand GM, Holden T, Chong CR, Goyal L, Fisher GA, Chen CT
BMC Cancer · 2026 Jun · PMID 42271289 · Full text
BACKGROUND: Multiple drugs targeting the human epidermal growth factor receptor-2 (HER2) have shown clinical activity in gastrointestinal (GI) cancers. How to best integrate these various options in clinical practice alo...
BACKGROUND: Multiple drugs targeting the human epidermal growth factor receptor-2 (HER2) have shown clinical activity in gastrointestinal (GI) cancers. How to best integrate these various options in clinical practice alongside conventional therapy, however, is unclear. METHODS: We assessed the clinical outcomes of 103 patients with advanced HER2-altered GI malignancies who received ≥ 1 line of anti-HER2 therapy at our institution between 2010 and 2023. RESULTS: Next-generation sequencing (NGS) detected an ERBB2 amplification in 66% (27/41) of tumors that were HER2 + by IHC/ISH. Conversely, all patients with ERBB2 amplification were HER2 + by IHC. In the second-line and beyond, trastuzumab plus pertuzumab had the longest median time to treatment discontinuation (7.9 months), followed by trastuzumab deruxtecan (5.0 months). Among 25 patients who received ≥ 2 anti-HER2 agents, 24% had more durable clinical benefit to their second-line HER2 therapy compared to their first, as measured by the growth modulation index. CONCLUSIONS: Multimodal HER2 testing is needed to accurately identify candidates for HER2-targeted treatment, as NGS alone misses a significant proportion of cases. Patients who develop resistance to one anti-HER2 agent may still achieve benefit from subsequent HER2-directed regimens. Early and serial treatment with HER2-directed agents should be considered for patients with HER2 + GI cancers.
A systematic review and meta-analysis of treatment-induced hypertension risks from androgen receptor pathway inhibitors in randomized controlled trials for prostate cancer.
Gong Q, Ge F, Chen T
BMC Cancer · 2026 Jun · PMID 42271285 · Full text
OBJECTIVE: Androgen receptor pathway inhibitors (ARPIs) have revolutionized prostate cancer treatment, but their cardiovascular safety profile requires comprehensive evaluation. This meta-analysis aims to examine the ass...
OBJECTIVE: Androgen receptor pathway inhibitors (ARPIs) have revolutionized prostate cancer treatment, but their cardiovascular safety profile requires comprehensive evaluation. This meta-analysis aims to examine the association between ARPI use and hypertension risk in prostate cancer patients. METHODS: We systematically searched PubMed, Web of Science, and ClinicalTrials.gov for randomized controlled trials comparing ARPIs with control. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models for all-grade and grade ≥ 3 hypertension. Subgroup analyses were performed by individual ARPI agents and combination therapies. RESULTS: Twenty-two studies (derived from 21 distinct randomized controlled trials) involving 22,420 patients were included for analysis. ARPIs significantly increased the risk of all-grade hypertension (RR 1.82, 95% CI 1.51-2.21, p < 0.001). Combination therapy with abiraterone plus enzalutamide showed the highest risk (RR 3.46, 95% CI 2.96-4.05), followed by enzalutamide monotherapy (RR 2.20, 95% CI 1.67-2.91) and abiraterone monotherapy (RR 1.46, 95% CI 1.20-1.78). For grade ≥ 3 hypertension, ARPIs significantly increased risk (RR 2.17, 95% CI 1.68-2.81, p < 0.001) with similar subgroup patterns. Darolutamide and apalutamide demonstrated relatively favorable cardiovascular safety profile among monotherapies. CONCLUSION: ARPI treatment significantly increases hypertension risk in prostate cancer patients, with substantial variability among specific agents and regimens. Combination therapy poses the highest risk, while darolutamide demonstrated a lower risk profile in this indirect comparison. These findings support routine blood pressure monitoring and aggressive management in patients receiving ARPI therapy, particularly those with pre-existing cardiovascular risk factors.
Estrogen metabolites in premenopausal women living in China, Mongolia, and the United Kingdom.
Houghton LC, Ganmaa D, Dos Santos Silva I … +8 more , Falk R, Lui ML, Ulanday KT, Gierach G, Xu X, Davaalkham D, Zheng W, Troisi R
BMC Cancer · 2026 Jun · PMID 42271280 · Full text
BACKGROUND: Breast cancer incidence is lower in women living in Asia than women living in North America and Northern Europe. However, large differences exist within Asia, for example, Mongolia's breast cancer rate is eve...
BACKGROUND: Breast cancer incidence is lower in women living in Asia than women living in North America and Northern Europe. However, large differences exist within Asia, for example, Mongolia's breast cancer rate is even lower than China's. Endogenous estrogens in Asian populations have been hypothesized to explain the disparity because of their strong positive correlations with breast cancer, though few studies have compared estrogen metabolites (EM) within Asia or between Asia and higher breast cancer risk countries. METHODS: We measured urinary concentrations of estradiol and estrone (parent estrogens) and 13 EM (non-parent estrogens) formed by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring in premenopausal women living in Ulaanbaatar, Mongolia (n = 282), Shanghai, China (n = 121), and the United Kingdom (n = 125). We performed analysis of variance (ANOVA) using a generalized linear model procedure to assess differences in hormone concentrations between British and Asian (Chinese and Mongolian), and Chinese and Mongolian. Exponentiated least square means were used to calculate percent differences. We compared differences in overall means adjusted for age, body mass index, and parity by country during the follicular, peri-ovulatory, and luteal phases. RESULTS: Total, parent, and non-parent estrogen concentrations were generally higher in British than Asian women, while the non-parent to parent ratio was lower. While parent estrogens appeared higher in Chinese compared with Mongolian women, differences did not reach statistical significance except for peri-ovulatory estrone; total estrogen metabolites in the 2-, 4-, and 16-pathways were higher in Mongolian than Chinese women. The non-parent to parent ratio was highest in Mongolian women followed by Chinese women, with British women having the lowest ratio. CONCLUSION: Total urinary estrogens, both parent and their metabolites, were higher in British compared with Asian women. Our data showing the ratio of non-parent to parent estrogens, possibility reflecting greater estrogen metabolism, in women living in Mongolia, with one of the lowest breast cancer rates globally, than in women living in China, and in Chinese compared with British women, are consistent with their relative breast cancer risks and suggestive of a potentially protective metabolic profile.
HEPACAM2 expression for prognostic stratification in rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy.
Shen EY, Yeh HW, Tsan DL … +3 more , Chang YC, Li CF, Yang CC
BMC Cancer · 2026 Jun · PMID 42271277 · Full text
BACKGROUND: Identification of molecular biomarkers associated with treatment response and survival outcomes may facilitate personalized therapeutic strategies in rectal cancer. HEPACAM2 (hepatocyte cell adhesion molecule...
BACKGROUND: Identification of molecular biomarkers associated with treatment response and survival outcomes may facilitate personalized therapeutic strategies in rectal cancer. HEPACAM2 (hepatocyte cell adhesion molecule 2), a member of the immunoglobulin superfamily, has been implicated in mitotic regulation and centrosome maturation and may influence tumor progression. Therefore, this study aimed to evaluate the prognostic significance of HEPACAM2 expression in patients with rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy. METHODS: Mining of a publicly available gene expression dataset (GSE35452) identified HEPACAM2 as one of the significantly upregulated in CRT-resistant tumors. Immunohistochemical assessment of HEPACAM2 protein expression was performed on pretreatment biopsy specimens from 343 patients with rectal adenocarcinoma who underwent neoadjuvant CRT between 1998 and 2017. Associations between HEPACAM2 expression and clinicopathological variables were examined using chi-square testing. Survival outcomes were evaluated using Kaplan-Meier estimation and Cox proportional hazards regression. RESULTS: High HEPACAM2 expression was associated with advanced pretreatment stage, nodal involvement, increased posttreatment residual disease, vascular and perineural invasion, and poor tumor regression (all p ≤ 0.005). In both univariable and multivariable analyses, high HEPACAM2 expression independently predicted worse disease-specific survival (HR 2.663, 95% CI 1.280-4.203, p = 0.005), locoregional recurrence-free survival (HR 4.311, 95% CI 1.130-5.960, p = 0.003), and metastasis-free survival (HR 5.711, 95% CI 2.657-12.278, p < 0.001). CONCLUSIONS: These findings suggest that HEPACAM2 expression may represent a novel prognostic biomarker for rectal adenocarcinoma, although prospective studies are required to confirm its clinical utility.
Prognostic significance of therapy-induced senescence and SASP dynamics in acute myeloid leukemia: a retrospective cohort study.
Ma B, Zhang L
BMC Cancer · 2026 Jun · PMID 42271269 · Full text
BACKGROUND: Chemotherapy constitutes the backbone of Acute Myeloid Leukemia (AML) treatment but often induces cellular senescence. While senescence initially halts tumor proliferation, the accumulation of senescent cells...
BACKGROUND: Chemotherapy constitutes the backbone of Acute Myeloid Leukemia (AML) treatment but often induces cellular senescence. While senescence initially halts tumor proliferation, the accumulation of senescent cells and the Senescence-Associated Secretory Phenotype (SASP) may promote leukemic survival and relapse. The clinical correlation between post-treatment senescence burden and AML prognosis remains poorly characterized. METHODS: We conducted a single-center retrospective study analyzing 128 newly diagnosed AML patients treated with standard induction chemotherapy between January 2019 and December 2023. Bone marrow samples were assessed at diagnosis and post-induction. Senescent cell burden was quantified via p16 and p21 expression, alongside Senescence-Associated β-galactosidase (SA-β-gal) activity using flow cytometry. Immune sub-clustering was performed to evaluate senescence in progenitor versus mature populations. SASP factors (IL-6, IL-8, TNF-α) were measured in bone marrow plasma by ELISA. Patients were stratified into High-Senescence and Low-Senescence groups based on median cut-off values. RESULTS: Induction chemotherapy significantly increased the proportion of senescent cells and normalized SASP levels compared to baseline (P < 0.001), with LSC progenitors exhibiting the highest senescence burden. High post-induction senescence burden was positively correlated with adverse cytogenetics and minimal residual disease (MRD) positivity. Senescence markers strongly correlated with IL-6 and IL-8, but not TNF-α. Patients in the High-Senescence group exhibited significantly inferior Event-Free Survival (median EFS: 8.5 vs. 18.2 months, P = 0.002) and Overall Survival (median OS: 14.2 vs. 26.5 months, P = 0.004). Multivariate Cox regression identified high IL-6 levels (HR 2.14, 95% CI 1.32-3.48) and elevated p16 (HR 1.98, 95% CI 1.15-3.40) as independent predictors of poor prognosis. CONCLUSION: Therapy-induced senescence creates a pro-tumoral microenvironment via SASP in AML. High senescence burden post-induction is a robust biomarker for poor outcomes, suggesting that senolytic strategies targeting these cells could improve therapeutic efficacy.
Examining bidirectional longitudinal relationships between physical activity and physical function in older breast cancer survivors: The Thinking and Living with Cancer study.
Artese AL, Zhou X, Small BJ … +22 more , Ahles TA, Ahn J, Bethea TN, Casagrande CC, Choi E, Cohen HJ, Extermann M, Graham D, Hall K, Isaacs C, Jim HSL, Kusters CDJ, McDonald BC, Nakamura ZM, Patel SK, Rentscher KE, Root JC, Saykin AJ, Van Dyk K, Zhai W, Carroll JE, Mandelblatt J
Cancer · 2026 Jun · PMID 42267689 · Full text
BACKGROUND: Older breast cancer survivors are susceptible to cancer- and treatment-related losses in physical function that can negatively affect daily living activities, mobility, and independence. Although physical act...
BACKGROUND: Older breast cancer survivors are susceptible to cancer- and treatment-related losses in physical function that can negatively affect daily living activities, mobility, and independence. Although physical activity can improve physical function, few studies have focused on older survivors or explored interrelationships between physical activity and physical function. Longitudinal bidirectional relationships between physical activity and physical function in breast cancer survivors and noncancer controls aged 60+ years were evaluated. METHODS: Survivors (aged 67 ± 7 years; n = 357) newly diagnosed with nonmetastatic breast cancer (stages 0-III) and noncancer controls (aged 67 ± 9 years; n = 254) were assessed at baseline (postsurgery and pre-systemic therapy among survivors) and annual visits for up to 36 months. Physical activity (steps per day) was assessed via actigraphy. The Timed Up and Go test (longer time indicates lower function) and 12-item Short Form Health Survey Physical Component Score evaluated physical function. Data were analyzed via random-intercepts cross-lagged panel models, with controlling for covariates; p values of ˂.05 were considered statistically significant. RESULTS: Starting from the 12-month visit, higher daily steps predicted better subsequent Timed Up and Go time among survivors and controls, and the magnitude of effect was stronger for survivors than controls at 24 months (post hoc comparison, p = .036; survivors: β = -0.420; p = .003; controls: β = -0.211; p = .032). Timed Up and Go time did not predict later daily steps. Associations between steps and the Physical Component Score showed similar patterns. CONCLUSIONS: Higher daily steps predicted better subsequent physical function, especially in survivors. These results highlight the importance of promoting physical activity during cancer survivorship care to maintain functional independence.
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