• Arginase 2 Downregulation in High-Grade Prostate Adenocarcinoma and Its Spatial Inverse Association with Tumor-Infiltrating Lymphocytes.
    1 week ago
    The interaction between metabolic enzymes and the immune microenvironment in prostate cancer is still complex. This study aimed to examine the relationship between Arginase 2 (ARG2) expression and tumor-infiltrating lymphocytes (TILs) in prostate adenocarcinoma patients, as well as its correlation with histopathological grading, thereby elucidating immunometabolic mechanisms within the Indonesian patient population.

    This observational analytic study utilized a cross-sectional design, incorporating 105 formalin-fixed paraffin-embedded (FFPE) tissue blocks of prostate adenocarcinoma obtained from referral hospitals in Makassar, Indonesia. Immunohistochemistry was used to find out how much ARG2 was expressed, and digital image analysis (QuPath) was used to get an objective H-Score. According to the International Immuno-Oncology Biomarkers Working Group guidelines, the density of TILs was measured on H&E-stained slides. Statistical analyses encompassed Spearman's rank correlation, the Kruskal-Wallis test, and the Wilcoxon Signed-Rank test for spatial analysis.

    The study population was predominantly characterized by high-grade tumors, with 45.7% categorized as Grade Group V (Gleason Score 9-10). The digital quantification of ARG2 was validated by manual scoring (r = 0.768, p < 0.001). There was no statistically significant correlation between ARG2 expression and TILs density on a global scale (r = 0.048, p = 0.630). Nonetheless, paired spatial analysis indicated a significant local disparity; tumor regions infiltrated by TILs demonstrated substantially diminished ARG2 expression relative to adjacent non-infiltrated regions (p = 0.009). Moreover, ARG2 expression exhibited a significant inverse correlation with WHO Grade Group (p < 0.001), indicating substantial downregulation in high-grade tumors.

    The expression of Arginase 2 is significantly reduced in high-grade prostate adenocarcinoma, signifying tumor dedifferentiation. Although ARG2 does not universally forecast immune infiltration, it influences the tumor microenvironment locally, with increased expression correlating with immune exclusion.
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  • Study of the Role of Circulating Cell-Free DNA in the Diagnosis of Cholangiocarcinoma.
    1 week ago
    Cholangiocarcinoma (CCA) is an aggressive biliary malignancy usually diagnosed at advanced stages because early symptoms are vague. Conventional serum markers, including carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), have limited sensitivity and specificity. Circulating cell-free DNA (cfDNA), particularly ALU-115, ALU-247 and DNA integrity index, may provide improved diagnostic accuracy by reflecting tumor-derived DNA fragmentation.

    A case-control study enrolled 160 subjects divided into four groups, each comprising 40 individuals: CCA (Group I), other hepatobiliary malignancies including hepatocellular carcinoma and pancreatic head cancer (Group II), benign biliary disorders (Group III), and healthy controls (Group IV). Clinical data, biochemical parameters, tumor markers, and cfDNA fragments were assessed. cfDNA was quantified by real-time PCR using ALU-115 (short fragments) and ALU-247 (long fragments). The DNA integrity index was calculated. Receiver operating characteristic (ROC) curves were used to determine diagnostic performance.

    Serum CEA and CA19-9 were significantly higher in Groups I and II compared with Groups III and IV (p < 0.001), but they showed limited discrimination between CCA and other malignancies. cfDNA markers demonstrated significantly higher values in CCA than in other groups (p < 0.001). Against Group II, ALU-247 >800 copies/ml yielded 80% sensitivity and 75% specificity, while DNA integrity >0.89 achieved 70% sensitivity and 90% specificity. Against Group III, ALU-115 >700 copies/ml showed 85% sensitivity and 90% specificity. Versus controls, an ALU-115 >580 copies/ml reached 95% sensitivity and 95% specificity.

    cfDNA concentrations and integrity indices outperform CEA and CA19-9 for distinguishing CCA from other malignancies, benign biliary disease, and healthy subjects. These findings support the incorporation of cfDNA-based assays as minimally invasive diagnostic adjuncts for CCA pending larger validation studies.
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  • Determinants of System and Patient Delays in Breast Cancer Diagnosis and Treatment: A Multi-Level Observational Analysis in a Tertiary Care Setting.
    1 week ago
    Delays in breast cancer diagnosis and treatment significantly impact patient outcomes. Understanding the determinants of system-related and patient-related delays is crucial for improving cancer care pathways.

    To identify and analyse the sociodemographic, clinical, psychological, and awareness factors associated with system and patient delays in breast cancer diagnosis and treatment in a tertiary care setting.

    A cross-sectional observational study was conducted at a tertiary care hospital involving 95 breast cancer patients. Participants were interviewed using a comprehensive questionnaire assessing sociodemographic factors, barriers and facilitators to care, clinical characteristics, and psychological factors. Bivariate and multivariate logistic regression analyses were performed to identify significant associations.

    Illiteracy (OR = 5.20, p = 0.007) and housewife status (p = 0.036) were significant predictors of patient delay. Major barriers included financial constraints (67.4%), fear of excessive treatment (40%), discomfort with male doctors (67.4%), and transportation challenges (66.3%). Healthcare provider recommendations (58.9%), female doctors (61.1%), and spousal support (62.1%) were key facilitators. Multivariate analysis revealed that the first point of care (p = 0.009), emotional distress (p = 0.041), and personal shyness (p = 0.007) significantly influenced delays. Homeopathy use was associated with delay (p = 0.010), while early breast self-examination practice was protective (p = 0.000).

    Delays in breast cancer care are multifactorial, stemming from sociodemographic disparities, cultural beliefs, psychological factors, and system-level challenges. Interventions addressing health literacy, gender-sensitive care, financial assistance, and family/workplace support are essential for reducing delays and improving treatment outcomes.
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  • Treatment Patterns and Survival Outcomes in a Real-World Cohort of 263 Patients with EGFR L858R-Mutant Non-Small Cell Lung Cancer: Focus on EGFR-TKI Selection.
    1 week ago
    Compare the treatment efficacy of EGFR TKIs in patients with non-small cell lung cancer with the EGFR L858R exon 21 mutation.

    This retrospective analysis included 263 patients with advanced non-small cell lung cancer harboring the EGFR L858R mutation who were treated with EGFR tyrosine kinase inhibitors (TKIs) at Nghe An Oncology Hospital, Vietnam, between January 2018 and June 2025. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and differences between groups were compared using the log-rank test. The association of clinical factors with survival outcomes was assessed using Cox proportional hazards regression models.

    The median progression-free survival (PFS) and overall survival (OS) for the study population were 14.1 months and 24.9 months, respectively. In the entire population (n=263), osimertinib demonstrated superior efficacy compared to first-and second generation EGFR TKIs (PFS: HR = 0.37, 95% CI: 0.21-0.63, p < 0.001; OS: HR = 0.31, 95% CI: 0.15-0.63, p = 0.001). In multivariate analyses (n = 232), afatinib was not associated with a statistically significant improvement in survival outcomes compared to first generation EGFR TKIs (PFS: HR = 0.70, 95% CI: 0.43-1.13, p = 0.143; OS: HR = 0.71, 95% CI: 0.42-1.19, p = 0.199). Subgroup analysis showed that the benefits of osimertinib were maintained in patients with malignant pleural effusion (PFS: HR = 0.40, 95% CI: 0.16-0.95, p = 0.040; OS: HR = 0.31, 95% CI: 0.11-0.87, p = 0.027).

    In patients with the EGFR L858R exon 21 mutation, our real-world data demonstrate that osimertinib is the most effective TKI, while afatinib offers no significant survival advantage over first-generation TKIs. This underscores the importance of mutation-specific treatment strategies.
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  • Cancer Distribution Pattern in the City of Kenitra, Morocco (2017-2022): A Pathology-Based Study.
    1 week ago
    Cancer epidemiological surveillance is essential for implementing an effective prevention policy. In Morocco, only two population-based cancer registries (Rabat and Casablanca), along with a limited number of local studies, provide data on cancer incidence. This report aims to describe the pattern of cancer incidence rates in the region of Kenitra.

    This was a pathology-laboratory-based retrospective and descriptive study of all newly diagnosed cancers in public and private pathology laboratories in Kenitra between January 2017 and December 2022. Data on gender, age, and cancer locations were collected from medical records. Statistical analysis was limited to descriptive statistics, including frequencies, percentages, crude incidence rates, and age-standardized rates.

    2,682 cancer cases were recorded, with 1,535 males (57.23%) and 1,147 females (42.77%). The female-to-male ratio is 0.74. The median age at diagnosis was 59 (55 for females and 62 for males). The crude incidence rate was 254 per 100,000 population (291 per 100,000 for males and 217 per 100,000 for females). The overall age-standardized rate (ASR) was 283 per 100,000 (162 per 100,000 for males and 120 per 100,000 for females). The leading cancers among males were prostate (34.31%), bladder (19.27%), skin (13.54%), non-Hodgkin lymphoma (5.34%), stomach (3.97%), lung (3.84%), and colon (3.84%). The leading cancers among females were breast (27%), skin (15%), cervix (8%), non-Hodgkin lymphoma (5%), thyroid (5.49%), uterus (5%), and stomach (3.83%).

    Our study is the first to explore the occurrence of cancers in the city of Kenitra. The high rates of bladder and skin cancer in this area warrant further epidemiological studies to identify etiological factors, develop control programs, and formulate prevention strategies.
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  • Augmented Reality-Based Breast Self-Examination Education and Its Effects on Knowledge and Perceived Behavioral Control Among Indonesian Adolescent Girls: A Quasi-Experimental Study.
    1 week ago
    Breast cancer is the most common malignancy among women, with an increasing burden among adolescents and young adults. Breast self-examination (BSE) is a simple and low-cost method for early detection; yet, its practice remains suboptimal in this age group. Augmented Reality (AR) is a promising approach to enhancing cancer education.

    This study aims to rigorously compare the effects of AR-based education and traditional learning on breast self-examination (BSE) knowledge and perceived behavioral control (PBC) among adolescent girls, with the goal of identifying the more effective approach for empowering this population.

    A quasi-experimental posttest-only non-equivalent control group design was conducted among tenth-grade female students at a public senior high school in Yogyakarta, Indonesia. A total of 140 adolescents were assigned to an intervention group (n = 70) or a control group (n = 70). The intervention group received AR-based BSE education using a three-dimensional mobile application, whereas the control group received lecture-based education with posters and leaflets. Knowledge and PBC were assessed three months after the intervention using validated, self-administered questionnaires, and data were analyzed using appropriate nonparametric tests (α = 0.05).

    The AR group demonstrated a substantially higher proportion of participants with high knowledge compared to the control group (71.4% vs. 28.6%; p < 0.001, r = 0.26), as well as significantly higher total knowledge scores (p = 0.002). Participants in the AR group were significantly less likely to perceive BSE as time-consuming, expensive, complex, or embarrassing (all p < 0.01). Notably, perceived behavioral control (PBC) increased in the AR group (p < 0.001, r = 0.767).

    AR-based education was superior to conventional learning, resulting in significant improvements in BSE-related knowledge, substantial reductions in perceived barriers, and a marked increase in perceived behavioral control among adolescent girls.
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  • Dosimetric Comparison of Three-dimensional Conformal Radiation Therapy (3D-CRT) vs Volumetric Modulated Arc Therapy (VMAT) for Primary Malignant Brain Tumors.
    1 week ago
    Advances in radiotherapy planning have led to better dose delivery and protection of organs at risk (OAR) in malignant brain tumors. Though three-dimensional conformal radiotherapy (3D-CRT) is still commonly used, Volumetric modulated arc therapy (VMAT) delivers highly precise doses with dynamic adjustments. This study compares dosimetric differences prospectively between 3D-CRT and VMAT in primary malignant brain tumors.

    Fifty (50) patients with confirmed malignant primary brain tumors who received postoperative or definitive radiotherapy were assessed. Each patient had CT simulations, target and OAR contouring, and two distinct plans: 3D-CRT and VMAT using 6 MV photons. Treatment was delivered as per VMAT planning. The dosimetric endpoints included PTV coverage (D2%, D50%, D98%), conformity index (CI), homogeneity index (HI), and OAR doses (optic nerves, optic chiasm, brainstem, cochlea, retina, lens, pituitary, and spinal cord).

    VMAT delivered significantly lower doses to some OARs compared to 3D-CRT. The Dmax to the right and left optic nerves was significantly lower with VMAT (24.77 Gy vs. 32.34 Gy, p=0.002; 27.35 Gy vs. 32.86 Gy, p=0.032). For the optic chiasm, both the Dmax and Dmean doses were significantly lower with VMAT (31.28 Gy vs. 36.32 Gy, p=0.036; 24.27 Gy vs. 30.77 Gy, p=0.019). The Dmean  for the right cochlea was greatly reduced (7.27 Gy vs. 15.97 Gy, p=0.007). Differences in doses to the brainstem, pituitary, retina, and lens were minimal and not statistically significant. The PTV metrics (D2%, D50%, D98%) showed no significant differences between the techniques. The conformity index was acceptable for both plans (VMAT 0.903; 3D-CRT 1.089). Homogeneity indices were similar.

    VMAT offers better sparing of several critical OARs, such as the optic pathways and cochleae, while maintaining similar PTV coverage compared to 3D-CRT. Both techniques meet acceptable dose limits, but VMAT may be preferred for tumors near sensitive structures.
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  • Outcomes of an Opportunistic Screening Mammography Program Using the Mobile Mammography Unit in Sindh, Pakistan.
    1 week ago
    This study evaluated opportunistic screening mammography outcomes in a mobile mammography unit (MMU), performed for breast cancer detection among populations with limited access to breast imaging in Pakistan.  Methods: This cross-sectional study was conducted among women undergoing screening at the MMU stationed at two secondary hospitals of Aga Khan University Hospital from March 2019 to March 2021. Women aged ≥40 years and those <40 years at high risk for breast cancer were screened. Performance indicators included the cancer detection rate (CDR), BI-RADS assessment, and recall rate.

    1042 women were screened at the MMU. The median age was 49 years. 76.6% of women underwent screening for the first time. 64.7% of women had dense or heterogeneously dense breasts; however, heterogeneously dense breasts constituted the largest proportion (57.1%). The overall recall rate was 65.5%, out of which breast ultrasound was advised in 59.8% for dense breasts and additional mammographic views in 10.3% because of suspicious findings. Biopsy was advised for 20 women, of whom 13 (65%) completed the biopsy, yielding 11 cancers (CDR 10.6 per 1,000), Of all the diagnosed malignancies, 8 were invasive, 2 were ductal carcinoma in situ and histology of one cancer was unknown, with 72.7% of invasive cancers being node negative.

    This cohort of a largely first-time screened population with dense breasts yielded a high CDR and predominantly early-stage, node-negative cancers. The elevated CDR highlights a substantial reservoir of undiagnosed disease in underserved populations. MMU-based screening is known to be effective at identifying early breast cancers; however, its deficiency in a low-middle-income country (LMIC), such as Pakistan, calls for the immediate establishment of screening programs, preferably in mobile units across the country. Integrating MMUs with targeted outreach, on-site diagnostic tools, and patient navigation may improve follow-up adherence and further enhance early detection efforts.
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  • Superiority of Adjuvant Hyperfractionated Radiotherapy Over Chemotherapy Following Radical Cystectomy.
    1 week ago
    Bladder cancer (LABC) after radical cystectomy (RC) is common, even with chemotherapy, and is associated with high morbidity and mortality. Therefore, this work aimed to investigate the effect and efficacy of adjuvant sandwich chemotherapy plus radiotherapy versus adjuvant chemotherapy alone for LABC after RC.

    This phase III trial was conducted in 125 patients with bladder cancer who underwent RC and were randomized to one of the following two adjuvant treatments. The chemotherapy plus RT arm received 2 cycles of gemcitabine and cisplatin before and after RT, with a 1-week break between chemotherapy and RT. The second arm, receiving chemotherapy alone, had 4 cycles of gemcitabine and cisplatin.

    LRF was significantly reduced in the combined group (P < 0.001); however, DM was comparable between groups (p = 0.3). Furthermore, 64.9% of patients in the combined group were still alive, compared with only 5.9% in the chemotherapy group. Moreover, the mean time to local failure was not significantly different between the two groups (24.0 ± 0.1 vs. 26.5 ± 9.8, p = 0.08, respectively, for the combined group compared with the chemotherapy arm), but the mean time to DM was significantly prolonged in the combined group compared with the chemotherapy group (51.2 ± 14.9 vs. 29.7 ± 12.1, p < 0.001, respectively).

    Adjuvant chemotherapy plus RT was associated with significant improvements in LRFS and improvements in OS compared with chemotherapy alone in LABC.
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  • Assessment of Anatomic Surface Contour Variations During Radiation Therapy in Oral Cavity Cancer Patients with Flap Reconstruction by Co-Registering Planning CT and Cone Beam CT Scan.
    1 week ago
    Oral cavity cancer (OCC) patients undergoing flap reconstruction during surgery present unique anatomical challenges during postoperative radiation therapy (PORT). Variations in body contour and internal anatomy can affect dose distribution and necessitate adaptive radiotherapy (ART). However, limited data is available regarding the frequency, timing, and causes of re-planning.

    To evaluate anatomical surface contour variations and the need for adaptive re-planning in OCC patients with flap reconstruction (OCCwFR) receiving PORT using co-registration of planning CT and cone-beam CT (CBCT).

    This prospective observational study included adult OCCwFR patients treated with curative-intent PORT. Daily portal imaging and weekly CBCTs were analyzed. Variations greater than 1 cm across three or more consecutive CBCTs were considered significant. Changes were categorized as progression, regression, internal target motion, or setup error. Factors associated with adaptive re-planning were recorded.

    Among 111 patients, 39 (35%) required re-planning. Regression was the predominant change (92%), mainly due to weight loss (80%), followed by edema resolution and tumor response. Re-planning occurred mostly around the 20th fraction. Progression-related changes were rare (5%) and occurred earlier (3rd week). No association was found between flap type and re-planning (p= 0.21). Weight loss strongly correlated with re-planning (χ²= 45.5, p< 0.0001) and mean volume reduction of 50 cc.

    Anatomical changes during PORT in OCCwFR patients are frequent, predominantly due to weight loss. Mid-treatment ART around the 5th week and proactive nutritional support are essential to maintain dosimetric accuracy and treatment efficacy.
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