• Artificial Intelligence/Machine Learning-Driven cfDNA Methylation Blood Test for Early Cancer Detection in Military Personnel With Environmental Toxin Exposure.
    2 weeks ago
    Military personnel face heightened cancer risks from exposure to burn-pit emissions, per- and polyfluoroalkyl substances (PFAS), jet fuel, and radiation. Veterans show elevated malignancy rates, and active-duty personnel remain vulnerable because of ongoing operational exposures, underscoring the need for early detection. Traditional screening methods are invasive and have limited sensitivity for early-stage disease. This study evaluates the feasibility of artificial intelligence/machine learning (AI/ML)-based cell-free DNA (cfDNA) methylation analysis for early cancer detection using publicly available civilian datasets, to inform future application in high-risk military populations.

    A Machine-Learning driven cfDNA methylation classifier framework was developed for early, minimally-invasive detection of cancers associated with toxic and occupational exposures. The platform uses bisulfite-sequenced data to identify differential methylation signatures that distinguish early stage hepatocellular carcinoma (HCC) from chronic liver disease and healthy controls. Proof-of-concept studies were conducted on public datasets for hepatocellular carcinoma (HCC) and esophageal cancer. Three cfDNA datasets (GSE93203, GSE63775, and PRJCA001372) were used for model training and k-fold cross-validation, and an independent WGBS liver-tissue dataset (PRJNA984754) served as a blind cross-assay validation set. Framework extensibility to other cancers was assessed through the EpiPanGI-Dx esophageal-cancer dataset (ESCC training, EAC validation).

    Across 3 HCC models, internal cross-validation achieved 84%-94% accuracy (AUC 0.80-0.88). On the independent WGBS dataset validated against the 3 trained models, classifiers generalized with 83%-100% accuracy (AUC 0.80-1.00). Clinical validation using biobank cfDNA plasma samples from early-stage hepatocellular carcinoma and cirrhosis controls is ongoing. The esophageal cancer model reproduced published performance (AUC 0.94 for ESCC, 0.90 for EAC), demonstrating generalizability beyond HCC.

    The cfDNA methylation-based AI/ML platform is promising for early multi-cancer detection in environmentally exposed military populations. Early results demonstrate feasibility and justify expansion to additional cancers, and larger clinical validation studies, potentially enhancing survivability through earlier intervention.
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  • Impact of dopants on X‑ray attenuation of 3D‑printed polymers for mammography and tomosynthesis spectra.
    2 weeks ago
    3D-printing enables the production of anthropomorphic breast phantoms for assessing image quality in digital mammography (DM) and breast tomosynthesis (DBT). 3D-printing materials must be selected carefully to mimic breast tissue attenuation for clinical spectra.

    This study investigates the impact on the effective X-ray attenuation coefficient (µeff) of polymer formulation and dopants (e.g., colorants) used in 3D-printing materials. It also analyses the impact on their equivalent glandular ratios (BR) relative to commercial materials (CIRS).

    Five base polymers (PLA, ABS, PETG, HIPS, RESIN) were selected among the catalogue of five manufacturers. A collection of nineteen variants (base polymer + color) was 3D-printed as step-wedges with thicknesses (t) from 0.5 to 5.5 cm and imaged on a clinical mammography system (DM: W/Rh with the anti-scatter grid, DBT: W/Al without grid, at 27, 29 and 31 kVp). The µeff(t) values were derived from the mean pixel value measured at each step of the logarithmically transformed images. As reference, µeff values were measured for the CIRS materials with well-known BR. A two-parameter empirical model was used to fit the values as: µeff(t) = µ0 /(1+kt), where µ0 corresponds to µeff at thickness tending to zero, and k is the decrease rate with thickness due to beam hardening and scatter. The impact of dopants on polymer attenuation was evaluated by analyzing both µeff and µ0 values. Based on µ0-BR relationships of CIRS materials, the corresponding BR values were computed for the investigated materials.

    For all acquisition conditions, some color variants of 3D-printed materials with the same base polymer exhibit noticeable differences in µeff, independently of the thickness, particularly for DM. For this modality, the maximum differences within µeff values of materials sharing polymer base decreased by 62% for PLA-based, 44% for PETG-based and 30% for ABS-based materials, when the thickness increases from 1.5 to 5.5 cm. For DBT, a lower variability of µeff values was observed. The materials best mimicking purely glandular and adipose tissues were selected based on µeff, µ0 and BR results. Specifically, relative differences in µ0 (averaged across kVp), reported as paired values (DM, DBT) were: (-3%, +1%) and (-1%, +4%) for PLA crystal silver and PLA blue versus CIRS with BR = 100% (glandular tissue); (+3%, +1%) for ABS white versus CIRS with BR = 0% (adipose tissue). According to the BR values derived for all acquisition conditions, PLA blue and PLA crystal silver mimicked glandular tissue (BR: 101%-109%, 95%-100%, respectively), while ABS white mimicked adipose tissue (BR: -2% to 8%). PETG translucent blue and RESIN corresponded to intermediate glandular ratios (BR ≈ 50%-70%).

    3D-printed materials sharing the same polymer base can exhibit substantially different attenuation for DM/DBT spectra, resulting in different BR equivalences due to formulation variations (e.g., pigments and dopants). Therefore, phantom developers should not rely solely on base polymer designations and declared density when selecting materials for production of breast phantoms; instead, the attenuation of each specific formulation needs to be verified and periodically re-evaluated under the intended mammography conditions.
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  • Commissioning and clinical positioning assessment of a novel surface-guided radiation therapy (SGRT) system at a C-Arm linear accelerator.
    2 weeks ago
    Surface-guided radiation therapy (SGRT) has been increasingly adopted in modern radiotherapy, enabling radiation-dose-free, marker-free patient positioning with high accuracy. A novel SGRT system, LUNA 3D (LAP, Lüneburg, Germany), featuring a browser-based interface, GPU-accelerated surface reconstruction, high frame rates, large field-of-view and virtual laser projection capabilities, has been commissioned and implemented clinically.

    This study reports comprehensive commissioning procedures and the associated results for the LUNA 3D system and evaluates its clinical impact on patient positioning accuracy for breast and pelvic cancer treatments.

    Commissioning tests were performed, including thermal drift, reproducibility, translational and rotational shift accuracy, camera occlusion assessment during gantry rotation, radiographic verification against cone-beam computed tomography (CBCT), and End-to-End dosimetric testing. Test results were compared using two reference surfaces: one captured by LUNA 3D (SGRT-reference) and the other derived from the CT external structure (SIM-reference). A clinical evaluation was conducted to compare CBCT-derived positioning corrections from 192 breast and 259 pelvic treatment datasets acquired in the periods before and after the clinical implementation of LUNA 3D, employing Welch's two-sample t-test and Cohen's d effect size.

    The thermal drift within the operating temperature range is ≤0.4 mm for all three axes. Across the reproducibility and translational/rotational shift tests, maximum deviations were ≤0.3 mm translational and ≤0.2° rotational with the SGRT-reference, and ≤0.8 mm translational and ≤0.2° rotational with the SIM-reference, the latter attributable to the difference introduced by the CT-derived reference surface. Radiographic verification showed agreement within 1.0 mm between LUNA 3D and CBCT corrections for both reference surfaces. End-to-End testing yielded CBCT residuals of 0.9-1.3 mm with 1.2% dosimetric deviation. All evaluated performance metrics are compared to the ESTRO-ACROP and AAPM TG-302 guidelines' tolerances. Clinical implementation resulted in significant positioning improvements: for breast treatments, 3D translational vector decreased 28.7% from 7.00 ± 4.35 mm to 4.99 ± 2.75 mm (p < 0.001, Cohen's d = 0.54); for pelvic treatments, 3D rotational vector decreased 24.0% from 2.31 ± 0.96° to 1.76 ± 0.67° (p < 0.001, Cohen's d = 0.66).

    LUNA 3D was successfully commissioned, meeting international SGRT guidelines. Clinical implementation produced statistically significant and clinically meaningful improvements in patient positioning accuracy with anatomical site-specific benefits. These findings establish LUNA 3D as a reliable SGRT technology that enhances positioning accuracy in routine clinical practice.
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  • Construction and Validation of a Risk Prediction Model for Cancer-Related Cognitive Impairment in Lung Cancer Patients.
    2 weeks ago
    Cancer-related cognitive impairment (CRCI) is a major clinical challenge faced by lung cancer patients during or after treatment. Early identification of at-risk populations by healthcare professionals is inadequate, and little is known about measures that can be taken to enhance their prevention. Existing systematic reviews and meta-analyses have summarized common risk factors for CRCI in lung cancer patients, but integrated predictive models based on holistic theoretical frameworks remain scarce.

    To construct a visual assessment tool for the identification of CRCI in lung cancer survivors based on the theory of unpleasant symptoms (TOUS), complementing existing predictive models with a multidimensional theoretical perspective.

    A prospective, observational, single-centre study.

    The present study was conducted in a major hospital in Urumqi, China, between October 2023 and July 2024. A total of 350 lung cancer survivors participated in this survey, which was divided into a training and validation group in a 7:3 ratio. Lasso regression and logistic regression analyses were employed to identify the risk factors for CRCI, construct a nomogram prediction model and test the prediction effect in the validation set. Model performance was evaluated using the area under the curve (AUC) and goodness-of-fit statistics, and the model was internally validated.

    A total of 350 lung cancer patients, comprising 245 in the training and 105 in validation groups, were included. Of these, 117 (33.4%) experienced CRCI. The predictive model identified significant predictors, including age, pathological stage, chemotherapy, post-traumatic stress disorder (PTSD), depression and social support scores. At the 32.3% optimal cut-off, the model had AUC values of 0.863 and 0.818 in the training and validation groups. Calibration plots demonstrated a strong correlation between predicted and observed rates, and decision curve analysis revealed optimal net benefit at threshold probabilities ranging from 10% to 80%.

    The risk prediction model constructed in this study, based on TOUS, demonstrates satisfactory predictive ability superior to some existing models. It integrates physiological, psychological and environmental factors, serving as a valuable complementary tool for healthcare professionals in identifying high-risk groups, particularly in clinical settings emphasizing holistic symptom management.
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  • Efficacy of a Stepped-Care Approach to Cognitive-Behavioural Therapy for Insomnia (Can-Sleep) in Adolescents and Young Adults With Cancer.
    2 weeks ago
    Poor sleep is a common issue among adolescents and young adults (AYA) with cancer. The present study describes the feasibility and impact of the Can-Sleep stepped-care intervention for AYA with cancer.

    A total of 51 AYA with cancer were screened. AYA who reported sleep disturbance (defined as insomnia severity index score [ISI] > 7) received self-managed cognitive behavioural therapy for insomnia (SMCBT-I) in the first instance (Step 1) followed by individual cognitive behavioural therapy for insomnia (ICBT-I) if symptoms continued (Step 2). AYA screened as high risk for intrinsic sleep abnormalities (e.g., obstructive sleep apnoea) were referred to a specialised service.

    Of the 51 AYA, 38 participants reported sleep disturbance. In total, 37 AYA commenced SMCBT-I, four attending the specialised sleep service prior. Thirty-one (84%) completed Step 1. Of these, 45% improved and required no further treatment, and 55% (17) were eligible for ICBT-I (ISI > 7). Following intervention, the SMCBT-I group showed a significant decline in insomnia symptoms (p < 0.001, d = 0.84). Among the 17 AYA continuing to report sleep disturbance, 11 (65%) were referred to ICBT-I, with 8 (73%) accepting and completing Step 2. Those who received the ICBT-I showed a significant reduction in insomnia symptoms (p = 0.007, d = 1.33).

    This study provides preliminary efficacy and acceptability of a stepped-care intervention for sleep disturbances in AYA with cancer. A stepped-care intervention may offer an effective and resource-efficient method for managing sleep disturbance in AYA with cancer.
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  • Real-World Outcomes of Olaparib Treatment in Japanese Patients With Metastatic Castration-Resistant Prostate Cancer Harboring BRCA Pathogenic or Likely Pathogenic Variants.
    2 weeks ago
    Olaparib has demonstrated clinical benefit in patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA pathogenic or likely pathogenic variants (PVs) in randomized clinical trials; however, multicenter real-world data in Japanese patients remain limited.

    This multicenter retrospective study included Japanese patients with mCRPC who received olaparib between 2021 and 2025 at four institutions. Eligible patients had pathogenic or likely pathogenic BRCA1/2 variants identified by comprehensive genomic profiling or BRCA-specific testing (BRACAnalysis). Disease progression was defined as prostate-specific antigen (PSA) progression or radiographic progression. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.

    Among 128 patients undergoing comprehensive genomic profiling, 18 (14%) were identified as having BRCA PVs, of whom 13 received olaparib. Among 239 patients tested by BRACAnalysis, 14 (6%) harbored BRCA PVs and all received olaparib. Overall, 27 patients with mCRPC harboring BRCA PVs were analyzed. The median duration of olaparib treatment was 8 months, with three patients treated for more than 30 months. One-year OS rate was 80.6%, with a median OS of 18.4 months, and 1-year PFS rate was 27.2% with a median PFS of 7.6 months. Grade 3 anemia occurred in 33% of patients and was manageable, with no grade 4 or 5 events observed.

    This multicenter retrospective study provides real-world data on olaparib treatment in Japanese patients with mCRPC harboring BRCA PVs. The observed outcomes and safety profile were generally consistent with previous reports, although interpretation is limited by the small sample size, retrospective design, and heterogeneity of prior treatments.
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  • Up to Four-Year Outcomes of Single-Fraction Stereotactic Radiosurgery for Small Brain Metastases: A Competing-Risk Analysis.
    2 weeks ago
    Single-fraction stereotactic radiosurgery (SRS) is recommended for small brain metastases (< 2 cm). However, long-term outcomes accounting for competing risks-particularly death, which precludes observation of local treatment failure (LTF)-remain limited.

    We retrospectively analyzed cumulative incidences of LTF, defined as tumor regrowth within the planning target volume, following 18 Gy single-fraction SRS (July 2014-December 2021) in patients with brain metastases. Patients with prior radiotherapy or surgery to the index lesion were excluded. Cumulative incidences of LTF, death without prior LTF, overall survival (OS), and progression-free survival (PFS) were estimated. Outcomes were compared between radioresistant (melanoma, sarcoma, renal cell carcinoma) and radiosensitive tumors. Subdistribution hazard ratios (SDHRs) and cause-specific hazard ratios (CSHRs) identified risk factors for each endpoint.

    Seventy-two patients (median age 62 years, IQR 55-68) with median tumor volume 0.3 cc (IQR 0.2-0.7) were followed for a median of 57.2 months (IQR 49.3-85.4). Thirty-three tumors were radioresistant and 39 radiosensitive. At 36 months, cumulative LTF was 62% (95% CI, 42%-77%) versus 31% (95% CI, 17%-46%) in radioresistant versus radiosensitive tumors (p = 0.011), whereas death without prior LTF was 19% (95% CI, 7%-34%) versus 46% (95% CI, 30%-61%) (p = 0.003). OS was 42% (95% CI, 28%-63%) and 36% (95% CI, 24%-55%), and PFS was 19% (95% CI, 9%-40%) and 23% (95% CI, 13%-41%), respectively. Radioresistant histology was associated with higher LTF hazard (CSHR 3.19; SDHR 3.91) and lower hazards of death without prior LTF (CSHR 0.37; SDHR 0.24), with no significant effect on OS or PFS. The 36-month cumulative incidence of radiation necrosis was 10% (95% CI, 4%-18%).

    Local control after 18 Gy SRS is poor in radioresistant brain metastases. Higher LTF incidence is amplified by lower competing mortality, highlighting the interplay between tumor biology and survival. These findings support competing risk-based analyses and consideration of alternative dose-escalation for high-risk tumors.
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  • Transthoracic versus Transhiatal Esophagectomy for Esophageal Squamous Cell Carcinoma.
    2 weeks ago
    Esophageal squamous cell carcinoma (ESCC) is associated with high morbidity and mortality, and esophagectomy remains the mainstay of curative treatment. The optimal surgical technique transthoracic esophagectomy (TTE) versus transhiatal esophagectomy (THE) continues to be debated due to differences in surgical invasiveness and the extent of lymphadenectomy. This study aimed to compare clinical and oncological outcomes of TTE and THE in patients treated for ESCC.

    This retrospective study included patients who underwent curative-intent esophagectomy for histologically confirmed ESCC between 2015 and 2023. Patients were categorized according to surgical approach (TTE vs THE), and demographic characteristics, perioperative data, pathological findings, postoperative complications, and survival outcomes were compared between the 2 groups. Complications were classified according to the Clavien-Dindo system. Disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan-Meier analysis.

    A total of 39 patients were analyzed (21 TTE, 18 THE). Baseline demographic features and most perioperative variables were comparable. TTE was associated with a significantly longer operative time and higher lymph node yield, whereas THE showed higher rates of intraoperative transfusion and pleural effusion. Other postoperative complications were similar between groups. The TTE approach demonstrated significantly better DFS (P = .004). No significant difference in OS was observed between the groups (P = .165). No additional clinical or pathological factors were associated with survival outcomes.

    TTE resulted in a greater lymph node yield and significantly improved DFS, indicating a clear oncologic advantage over the transhiatal approach.
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  • Emergency Gynecologic Surgery Outcomes During Working and Off-Hours.
    2 weeks ago
    To compare perioperative outcomes of emergency gynecologic surgeries performed during working hours and off-hours, and to evaluate temporal trends in surgical approach, particularly laparoscopy.

    This retrospective cohort study included patients who underwent emergency surgery for ovarian torsion, ovarian cyst rupture, or ruptured tubal ectopic pregnancy between January 1, 2020 and October 1, 2025 at a tertiary referral center. Patients were grouped according to surgical timing as working hours or off-hours. Demographic characteristics, surgical approach, operative time, hemoglobin decrease, transfusion requirement, hospital stay, intraoperative and postoperative complications, and reoperation were compared within each diagnostic group. Annual trends in surgical approach were also analyzed, and multivariable linear regression assessed the association of off-hours surgery with operative time and length of hospital stay.

    A total of 386 patients were included: 69 with ovarian torsion, 77 with ovarian cyst rupture, and 240 with ruptured tubal ectopic pregnancy. Most procedures were performed during off-hours. In ovarian torsion and ovarian cyst rupture, perioperative outcomes were comparable between groups. In ruptured tubal ectopic pregnancy, operative time was longer during off-hours than during working hours and remained independently associated with off-hours surgery after adjustment, while hemoglobin decrease, transfusion requirement, hospital stay, complications, and reoperation rates were similar. The proportion of laparoscopic procedures increased from 17.9% in 2020 to 90.0% in the first 9 months of 2025.

    Off-hours emergency gynecologic surgery showed largely comparable outcomes to working-hours surgery. The marked shift toward laparoscopy suggests increasing integration of minimally invasive surgery into emergency gynecologic practice.
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  • Trop2-targeted PET/CT imaging with 68Ga-MY6349 improves diagnostic accuracy and influences clinical management in breast cancer.
    2 weeks ago
    Rationale: Trophoblast cell-surface antigen 2 (Trop2) is an essential therapeutic target in breast cancer, yet non-invasive methods for assessing its expression and predicting response to Trop2-directed antibody-drug conjugates (ADCs) remain limited. We aimed to evaluate the diagnostic accuracy of 68Ga-MY6349 positron emission tomography/computed tomography (PET/CT) in patients with breast cancer and assess its impact on clinical decision-making. Methods: We prospectively enrolled 73 patients with suspected or confirmed breast cancer who underwent both 68Ga-MY6349 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT from December 2024 to April 2025. Lesion-based diagnostic performance was compared using histopathology and follow-up imaging as reference standards. Treatment decisions were recorded before and after 68Ga-MY6349 PET/CT. Serial 68Ga-MY6349 PET/CT was performed to assess the early metabolic response in three patients with triple-negative breast cancer receiving sacituzumab tirumotecan. Results: 68Ga-MY6349 PET/CT identified more malignant lesions (564 vs. 436) and fewer false positives (2 vs. 40) than 18F-FDG PET/CT. In the initial-staging cohort (n = 30), 68Ga-MY6349 PET/CT led to TNM stage upgrades in 6/30 patients (20%) and treatment modifications in 4/30. In the restaging cohort (n = 43), clinical management was altered in 5/43 patients (12%) owing to the identification of additional metastatic lesions or rectification of false-positive findings via 68Ga-MY6349 PET/CT. 68Ga-MY6349 PET/CT yielded higher overall tumor uptake (median maximum standardized uptake value (SUVmax), 5.9 vs. 4.1; P < 0.001) and improved lesion conspicuity, particularly in lymph node and metastatic lesions. Exploratory analysis in three patients receiving Trop2-ADC therapy showed that early changes in 68Ga-MY6349 uptake after two treatment cycles were concordant with the subsequent clinical response. Conclusions: 68Ga-MY6349 PET/CT demonstrated superior diagnostic performance to 18F-FDG PET/CT in breast cancer staging and diagnosis, directly influencing therapeutic strategies. Preliminary findings from the triple-negative breast cancer cases suggest that early changes in SUVmax may be associated with the treatment response to Trop2-targeted ADC therapy, warranting further prospective validation in larger patient populations.
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