• Management of potentially curable colorectal lung metastases with synchronous systemic therapy and percutaneous image-guided thermal ablation.
    3 weeks ago
    To assess the survival benefit of synchronous systemic therapy plus thermal ablation (TA) in oligometastatic colorectal lung metastases (CRLM) and identify independent prognostic factors.

    Optimizing the integration of systemic therapy and TA for potentially curable CRLM remains a significant clinical challenge.

    This study employed a retrospective cohort design, including 326 patients who underwent TA treatment at six tertiary medical centers from March 2014 to October 2022. Patients were categorized into synchronous therapy, upfront ablation, delayed ablation, and no systemic therapy groups based on the timing of systemic therapy relative to TA. Kaplan-Meier analysis and log-rank tests were used to assess survival outcomes.

    Synchronous systemic therapy yielded the longest median progression-free survival (PFS) (22.0 months) and overall survival (OS) (61.3 months) compared to delayed ablation (13.0 and 49.2 months, respectively) and no systemic therapy (11.9 and 29.3 months, respectively) (all p < 0.05). Synchronous systemic therapy was an independent protective factor for PFS [hazard ratio (HR) = 0.493] and OS (HR = 0.211). Independent risk factors for local tumor progression included tumor size ≥3 cm (HR = 1.75) and peridiaphragmatic location (HR = 1.48). For PFS, independent predictors included tumor numbers (p < 0.001), synchronous metastases (HR = 1.431), and extrapulmonary metastases (p = 0.001). OS was adversely influenced by tumor burden (p < 0.05), extrapulmonary metastases (p < 0.001), and mediastinal lymph node involvement (HR = 1.518).

    Synchronous systemic therapy combined with TA significantly enhances PFS and OS in potentially curable oligometastatic CRLM patients.
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  • Exploratory Analysis of Candidate Gene SNPs in Relation to Cervical Cancer Susceptibility in Georgian Women.
    3 weeks ago
    IntroductionCervical cancer (CC) is the third most prevalent malignancy among women worldwide. Candidate gene studies have identified multiple single nucleotide polymorphisms (SNPs) that are associated with an increased risk of CC. The objective of this study was to examine the relationship between 8 specific single-nucleotide polymorphisms (SNPs) and the risk of cervical cancer in the Georgian population.MethodsThe present study employed a prospective case-control design, with 40 patients diagnosed with CC and 45 healthy women. A total of 8 single-nucleotide polymorphisms (SNPs) were genotyped using the TaqMan genotyping assay: rs7579014, rs11263763, rs7726159, rs6897196, rs2853672, rs635634, rs231775, and rs2304204.ResultsOur analysis demonstrated that rs7579014 (BCL11A, G/A), rs7726159 (TERT, C/A), and rs6356634 (ABO, T/A) were associated with an increased risk of cervical cancer in Georgian patients. However, following the implementation of the Benjamini-Hochberg correction, only rs6356634 (ABO T/A) and rs7579014 (BCL11A G/A) remained statistically significant. A lack of statistically significant correlation was identified between the genetic variants rs11263763, rs6897196, rs2853672, rs2304204, and rs231775 and susceptibility to cervical cancer.ConclusionsThis study represents the first attempt to investigate SNP associations in women with cervical cancer in Georgia. The findings indicate that SNP-based analysis may hold promise for the early identification of susceptibility to cervical cancer, and potentially to other cancers. Nevertheless, further research involving larger sample sizes is required to validate and strengthen these preliminary observations.
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  • Meeting physical activity guidelines in conjunction with higher protein intake: associations with appendicular lean soft tissue index in middle aged adults with cancer.
    3 weeks ago
    Loss of muscle mass is a common concern among patients with cancer. The aim of this study was to examine whether meeting the World Health Organization physical activity guidelines in combination with a higher vs. lower than the recommended daily allowance (RDA) protein intake is associated with greater appendicular lean soft tissue index (ALSTI) in adults aged 40-59 years with cancer from the National Health and Nutrition Examination Survey.

    Participants were categorized by physical activity levels (moderate ≥ 150 min/week or vigorous ≥ 75 min/week) and protein intake (> 0.8 vs. ≤ 0.8 g/kg/day) assessed via two interviewer-administered 24-h dietary recalls. ALSTI was calculated using dual-energy X-ray absorptiometry (kg/m2). Linear regression models estimated associations, adjusting for demographic, clinical, and dietary covariates.

    Among 169 participants (mean age 51.0 ± 5.6 years; 69% women, mean ALSTI 7.74 ± 1.66 kg/m2), those meeting vigorous or moderate physical activity guidelines with higher protein intake did not show a significant association with ALSTI in the fully adjusted models (vigorous: β = 0.08, standard error (SE) 0.12, p = 0.53; moderate: β = -0.05, SE 0.15, p = 0.76). However, a significantly positive link was found in those meeting both vigorous and moderate physical activity (β = 0.40, b SE 0.02, p < 0.01).

    Meeting vigorous or moderate physical activity guidelines in combination with higher vs. lower protein intake was not associated with ALSTI in adults with cancer. However, meeting both was positively linked to ALSTI. Longitudinal and interventional studies using objective measures and longitudinal designs are needed to clarify the role of physical activity with adequate protein intake in preserving muscle health in this clinical population.
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  • PRIME: an interpretable artificial intelligence model based on liquid biopsy improves prediction of progression risk in non-small cell lung cancer.
    3 weeks ago
    Despite the predictive impact of circulating tumor DNA (ctDNA) minimal residual disease (MRD), accurate prediction of failure risk after curative-intent treatments for early-stage or localized non-small cell lung cancer (NSCLC) patients to guide personalized therapy remains challenging. This study aimed to develop and validate an interpretable artificial intelligence-assisted model using global data resources.

    Liquid biopsy data, blood-based genomic alterations, clinicopathological features, and survival outcomes of stage I-III NSCLC patients who underwent surgery or definitive chemoradiotherapy were collected from 6 cohorts. PRIME (Progression Risk prediction by Interpretable Machine learning on ctDNA-MRD, Mutations, and clinical-therapeutic features) was trained by 6 machine learning algorithms across 4 cohorts and validated in 2 independent cohorts. Model performance was evaluated by the area under the curve (AUC) and interpreted by SHapley Additive exPlanations (SHAP). Whole-exome sequencing (WES) or whole-genome sequencing (WGS) of tumor tissue from 430 stage II-III NSCLC patients and RNA-sequencing (RNA-seq) data from 1149 subjects, sourced from The Cancer Genome Atlas, were used to validate the prognostic effect of mutations identified in peripheral blood and investigate the underlying mechanisms.

    A global dataset encompassing 781 blood samples from 493 patients was analyzed. Clinical stage, pre-treatment ctDNA, post-treatment MRD, blood-based Kelch-like ECH-associated protein 1 (KEAP1), serine/threonine kinase 11 (STK11), and cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations, and treatment modality were significantly associated with the risk of disease progression and were thereby included in the model training. WES/WGS and RNA-seq confirmed the poor prognostic effect of KEAP1, STK11, and CDKN2A mutations, which were characterized by the suppressive tumor microenvironment and attenuated humoral immunity. The neural network (NN) model exhibited optimal prediction of treatment failure risk in the training (AUC = 0.85, 95% CI 0.81-0.89) and validation sets (AUC = 0.82, 95% CI 0.74-0.89). SHAP analysis indicated that MRD (+0.306), treatment modality (+0.128), and pre-treatment ctDNA (+0.043) ranked in the top 3 contributions. NN-PRIME outperformed single liquid biopsy biomarkers and clinical-therapeutic signatures, and demonstrated consistent robustness across different clinical scenarios. High-risk patients identified by NN-PRIME had poorer prognoses but derived significant benefits from adjuvant therapy after surgery.

    As an interpretable model integrating readily-accessible and crucial clinical-genomic predictors, PRIME achieves enhanced performance, allowing for early outcome prediction, refined risk stratification, and personalized clinical decision-making.
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  • [Clinical and histopathological characteristics of 19 cases of orbital diffuse large B-cell lymphoma].
    3 weeks ago
    Objective: To investigate the clinical and histopathological characteristics of orbital diffuse large B-cell lymphoma (O-DLBCL). Methods: It was a retrospective case series study. The clinical data of patients diagnosed with O-DLBCL in Xi'an People's Hospital (Xi'an Fourth Hospital) and Shaanxi Eye Hospital from January 2016 to December 2024 were included. The clinical manifestations, imaging and pathological characteristics of the patients were collected. Immunohistochemical indicators such as CD20, C-MYC, CD10, Bcl-2, Bcl-6, MUM1, P53 and CD30 were detected by immunohistochemistry EnVision method, and they were typed according to the Hans method. Fisher's exact probability method was used for data analysis. Results: A total of 19 patients (19 eyes) were included, including 9 males and 10 females. The median age was 56.0 (50.3, 63.0) years, and the range was 30~83 years. There were 9 cases in the left eye and 10 cases in the right eye. Among them, 17 cases were primary O-DLBCL and 2 cases were secondary O-DLBCL. The clinical manifestations of the patients included exophthalmos in 16 cases, eye movement restriction in 14 cases, eyelid swelling in 15 cases, eyelid drooping in 4 cases, orbital swelling and pain in 11 cases, positive intraorbital pressure in 10 cases, conjunctival hyperemia and edema in 9 cases, lacrimation in 5 cases, diplopia in 4 cases, and visual acuity loss in 3 cases. Imaging manifestations showed irregular soft tissue density shadows in the orbit, infiltrative growth, invasive growth that could invade surrounding soft tissues or orbital bones, 3 cases invaded the maxillary sinuses or nasal sinuses, and 6 patients were considered benign lesions on imaging. The median maximum diameter of tumors was 2.2 (1.0, 3.0) cm, and the range was 0.6-5.0 cm. 5 cases involved the lacrimal glands, 2 cases involved the eyelids, 15 cases were histologically typed as centroblasts, and 4 cases were immunoblasts; According to the Hans typing method, there were 13 cases of non-erminal center b-cell-like (non-GCB) type and 6 cases of GCB type. Immunohistochemistry showed that 16 patients were positive for Bcl-2, 11 cases were positive for C-MYC, 9 cases were co-expressed for Bcl-2 and C-MYC, 3 cases were positive for CD30, 11 cases were positive for P53, and 13 cases had a high proliferation index (Ki67≥80%). All 19 patients underwent intraorbital mass resection, of which 8 were partial mass resection, 11 cases were complete mass resection, and 3 patients underwent intranasal or intramaxillary sinus mass resection at the same time. 16 patients were followed up for 2~48 months, of which 10 patients survived, 6 patients died, 1 case developed lung metastasis after 2 months of follow-up, and the rest did not have lymphoma from other sites. There are 8 patients treated with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine combined with prednisone) for 2~9 courses, of which 3 cases had complete remission, 4 cases had partial remission, and 1 case died after treatment. Conclusion: O-DLBCL is mostly a centroblastic type and a non-GCB type, with high Ki67 and high dual expression ratios of Bcl-2 and C-MYC, and should be actively treated to reduce its mortality rate.
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  • [Optical coherence tomography angiography features of choroidal melanotic tumors].
    3 weeks ago
    Objective: To describe and compare the internal vascular features of choroidal melanoma (CM) and choroidal nevus on optical coherence tomography angiography (OCTA). Methods: This cross-sectional study included patients clinically diagnosed with CM or choroidal nevus at Beijing Tongren Hospital between July 2019 and March 2025. Tumor-centered OCTA images were acquired, and the intrinsic tumor vasculature was reconstructed on two en face planes, the choriocapillaris slab and the full-thickness choroid slab. The malignant transformation risk of choroidal nevus was assessed using the multimodal imaging-based TFSOM-DIM criteria. Nevi with two or more high-risk features were classified as high-risk nevi, and the OCTA features of high and low-risk nevi was analyzed. The OCTA features were compared between the CM and nevus groups using the χ² test or Fisher's exact test. Results: A total of 95 eyes (95 patients) were included, consisting of 49 right eyes and 46 left eyes. There were 45 males (47.4%) and 50 females (52.6%), with a mean age of (47.6±14.1) years. All patients had unilateral involvement. The CM group included 67 patients (67 eyes), with 35 right eyes and 32 left eyes, comprising 36 males (53.7%) and 31 females (46.3%), with a mean age of (47.1±14.3) years. The choroidal nevus group included 28 patients (28 eyes), with 14 right eyes and 14 left eyes, consisting of 9 males (32.1%) and 19 females (67.9%), with a mean age of 48.8±13.6 years. There were no significant differences between the two groups in eye laterality (χ²=0.04, P=0.842), age (t=0.53, P=0.299), or sex distribution (χ²=3.69, P=0.055). In the choroid en face slab, disorganized vascular networks and vascular loops were observed in 66 CM cases (98.5%) and 14 nevus cases (50.0%; χ²=34.95, P<0.001). In the choriocapillaris en face slab, patchy avascular areas were detected in 54 CM cases (80.6%) and 9 nevi (32.1%; χ²=20.79, P<0.001), while the intrinsic tumor vasculature was present in 52 CM cases (77.6%) and 8 nevi (28.6%; χ²=20.41, P<0.001). Two distinct vascular patterns were identified within choroidal nevi on the choroid slab: 14 nevi (50.0%) exhibited diffusely attenuated flow signals without identifiable tumor vasculature, whereas the other 14 nevi (50.0%) demonstrated melanoma-like disorganized vascular networks. Among 17 low-risk and 11 high-risk nevi, melanoma-like disorganized vascular networks were present in 9 low-risk nevi (29.4%) and 5 high-risk nevi (81.8%), with a statistically significant difference (χ²=7.34, P=0.018). Conclusion: In OCTA images, CMs and choroidal nevi exhibit different internal vascular networks. CMs typically exhibit disorganized vasculature with vascular networks and loops, whereas choroidal nevi more often show attenuated flow signals or finer, more orderly vascular structures. The presence of melanoma-like disorganized vascular networks in choroidal nevi may significantly predict malignant transformation and serve as an imaging indicator for identifying high-risk nevi.
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  • Nephrotoxicity and associated risk factors in patients treated with pemetrexed.
    3 weeks ago
    Purpose: Pemetrexed causes renal impairment. However, few studies have investigated the risk factors associated with pemetrexed-induced renal impairment. This study aimed to investigate the incidence of nephrotoxicity in patients receiving pemetrexed in combination with carboplatin and to identify the associated risk factors. Methods: This single-center retrospective study included patients with lung cancer (including malignant mesothelioma) who underwent pemetrexed-based treatment between May 2019 and August 2022. Nephrotoxicity incidence was evaluated according to the Kidney Disease Improving Global Outcomes diagnostic criteria, and risk factors for nephrotoxicity during pemetrexed treatment were identified using logistic regression analysis. Results: Renal impairment occurred in 17 of 108 patients (15.7 %), with many experiencing irreversible renal function decline after its onset. The risk factors for nephrotoxicity during pemetrexed-based treatment were identified as the total number of cycles (≥ 10) (odds ratio: 7.94, p < 0.01) and its combination with any two non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs), or diuretics (odds ratio: 6.30, p < 0.01). Conclusion: Patients receiving pemetrexed treatment are at risk of developing renal impairment, with risk potentially increasing with the number of treatment cycles and concomitant use of NSAIDs, ACEIs/ARBs, or diuretics. However, further studies are required to confirm these findings.
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  • NKG2D genetic variants and cancer susceptibility: Integrating case-control evidence with meta-analysis.
    3 weeks ago
    Lymphomas are biologically heterogeneous malignancies with multifactorial etiologies involving genetic, environmental, and immune dysregulation. The functional variant rs1049174 SNP in the KLRK1 gene (encoding NKG2D) regulates NKG2D expression and modulates NK cells immune surveillance pathways, which may influence lymphoma susceptibility. We investigated this association through a two-stage case-control study and meta-analysis. First, we analyzed 246 diffuse large B-cell lymphoma (DLBCL) patients and 599 healthy controls (exploratory cohort), followed by a confirmatory cohort of 234 non-Hodgkin lymphoma (NHL)/Hodgkin lymphoma (HL) patients. Genotype frequencies were assessed via chi-square tests, with odds ratios (ORs) calculated for risk associations. A systematic review and meta-analysis of 10 studies, including our cohorts (3,785 cases and 4,129 controls), testing rs1049174 and cancer risk was also conducted. In the exploratory cohort, the GG genotype showed no significant association with overall lymphoma risk (OR = 0.83; 95% CI: 0.61-1.13; *p* = 0.25). However, in NHL, the GG genotype was underrepresented (OR = 0.75; 95% CI: 0.57-0.99; *p* = 0.02). Pooled lymphoma analysis revealed a protective effect (OR = 0.78; 95% CI: 0.62-0.99; *p* = 0.03). Meta-analysis confirmed a significant protective role of the GG genotype against cancer (OR = 0.71; 95% CI: 0.63-0.79), despite heterogeneity and potential publication bias. Our findings suggest that the rs1049174 GG genotype is associated with reduced lymphoma susceptibility, particularly in NHL, underscoring the importance of immunogenetic variants in lymphomagenesis. Further functional and clinical studies are needed to elucidate the mechanistic basis of this association.
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  • Exploring the influencing factors of subjective cognitive function in patients with advanced cancer pain: a cross-sectional study utilizing latent profile analysis.
    3 weeks ago
    Subjective cognitive function in patients with advanced cancer pain is frequently overlooked in clinical practice. The study employs latent profile analysis to categorize subjective cognitive function subtypes in patients suffering from advanced cancer pain and examines the factors influencing these subtypes. A survey involving 220 patients with advanced cancer pain utilized a general information questionnaire, the functional assessment of cancer therapy-cognitive (FACT-Cog) scale, the numerical rating scale (NRS), the patient health questionnaire-9 (PHQ-9), and the generalized anxiety disorder-7 (GAD-7). Latent profile analysis was applied to classify subjective cognitive function, and multiple logistic regression analysis was used to determine the influencing factors for each category. Out of 220 questionnaires, all were valid. The average FACT-Cog score was 90.20 (SD = 22.69), with 24.5% of patients exhibiting cognitive impairment. The PHQ-9 score averaged 9.21 (SD = 6.17), and the GAD-7 score averaged 8.02 (SD = 4.16). Latent profile analysis identified three subjective cognitive function groups: High subjective cognitive function group (7 patients, 3.2%), medium subjective cognitive function group (162 patients, 73.6%), and low subjective cognitive function group (51 patients, 23.2%). Depression, anxiety, age, education level, average 24-hour NRS score, and breakthrough pain frequency were identified as significant influencing factors across the subjective cognitive function profiles. The subjective cognitive function of patients with advanced cancer pain demonstrates distinct classification characteristics, primarily influenced by depression, anxiety, age, education level, pain scores, and the frequency of breakthrough pain. When devising cancer pain management strategies, it is crucial to develop targeted subjective cognitive interventions tailored to the specific profiles of these patients.
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  • Accuracy of AI-based raman spectroscopy in the diagnosis of gastric cancer: a systematic review and meta-analysis.
    3 weeks ago
    Gastric cancer (GC) remains a significant global health challenge with high mortality rates, often due to late-stage diagnosis. We hypothesize that Raman spectroscopy (RS) (a modern minimally invasive technique that uses light to analyze the molecular composition of tissue, generating a unique "fingerprint" that reveals biochemical details, distinguishing between normal and diseased tissues.) when combined with Machine learning (ML) would provide accurate and expedite approach of detecting GC. We aim to meta-analyze the diagnostic accuracy of ML-enhanced RS in differentiating GC component from normal tissue. This study was conducted following PRISMA-DTA guidelines. We searched PubMed, Scopus, Web of Science, VHL, and Google Scholar up to the end of February 2025. with an updated search conducted on 14 July 2025. We included any peer-reviewed manuscript that assessed ML-based RS technique for detecting GC components against normal control during endoscopy and reported sufficient data to construct 2 × 2 contingency table for assessing basic diagnostic metrics such as the sensitivity and specificity were included. Methodological quality of studies deemed eligible was assessed using QUADAS-2 risk of bias tool. Data on true positives, true negatives, false positives, and false negatives were extracted to calculate pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC) using R software. Heterogeneity was assessed with I2 statistics and Deeks' funnel plot was employed to examine potential publication bias. Moreover, we further subgrouped individual study metrics based on source of sample, RS technique, AI model, and the experimental context to assess their role in solidify results by controlling several confounders for heterogeneity. A total of 28 studies were enrolled comprising 2,392 patients and 8861 gastric spectra. Twenty-one studies (75%) applied per-spectra approach to analyze the diagnostic utility for GC tissue detection from non-pathological tissue. On the other hand, seven studies (25%) approached analysis as of per-patient stratification evaluating GC patients from healthy subjects. The pooled estimates of the sensitivity and specificity of per spectra approach yielded 92% (95% CI: 88-95%) and 93% (95% CI: 89-96%), respectively, and the AUC was 0.955. On the other hand, the pooled analysis of studies implemented per patient assessment approach yielded excellent sensitivity, specificity, and AUC as well with 95% (95% CI: 87-98%), 93% (95% CI: 89-95%), 0.928, respectively. Subgroup analyses showed that studies using the KNN model demonstrated the highest diagnostic accuracy. Conventional Raman spectroscopy also achieved superior performance across most metrics. Serum-based samples yielded higher sensitivity and specificity than tissue samples, though the limited number of serum studies warrants cautious interpretation. In vitro studies showed slightly better diagnostic accuracy than in vivo studies, although the difference was not statistically significant. Substantial heterogeneity was observed across per-spectra studies (I² = 82.1% for sensitivity and 91.2% for specificity), but no significant between-study variation was observed in per-patient analyses (I² = 27.3% for sensitivity and I² = 0% for specificity). No substantial publication bias was detected based on Deeks' funnel plot asymmetry test, with p = 0.394 for the per-spectra analysis and p = 0.858 for the per-patient analysis. Our meta-analyses' results provide strong evidence that ML-enabled RS from different body sources and across various ML algorithms subtypes significantly improve the GC detection rate and is superior at differentiating GC from healthy tissue during upper GI endoscopy. This approach led to a more precise and real-time decision-making regarding biopsy and excision, given our excellent diagnostic accuracy and low between-study heterogeneity that we obtained, integrating ML-enhanced detection of significant spectra into clinical workflows as valuable diagnostic adjunct particularly during the endoscopy will optimize false negative rate and overall patient outcomes.
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