• Real-world Outcomes of Trifluridine/Tipiracil With or Without Bevacizumab in Metastatic Colorectal Cancer: A Retrospective Cohort Study.
    1 week ago
    Trifluridine/tipiracil (FTD/TPI) is an established treatment for refractory metastatic colorectal cancer (mCRC), and recent clinical trials have demonstrated improved survival with the addition of bevacizumab. However, real-world evidence regarding this combination therapy, particularly in patients previously treated with bevacizumab and its positioning in later-line treatment strategies, remains limited.

    We conducted a retrospective cohort study of patients with mCRC treated with FTD/TPI with or without bevacizumab at our institution. Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method and log-rank test. A Cox proportional hazards model was used to estimate hazard ratio (HR). Subgroup analyses were performed according to prior bevacizumab exposure. Additionally, exploratory analyses were conducted to evaluate treatment sequencing with regorafenib.

    A total of 101 patients were included (FTD/TPI: n=42; FTD/TPI plus bevacizumab: n=59). The combination therapy was associated with significantly improved OS (HR=0.53, 95%CI=0.33-0.86, p=0.009) and PFS (HR=0.44, 95%CI=0.28-0.69, p<0.001). These associations remained significant in multivariate analyses. Subgroup analyses showed a consistent benefit of the combination therapy. In exploratory analyses, prior regorafenib use was associated with longer PFS (HR=0.32, p=0.002).

    In this real-world study, the addition of bevacizumab to FTD/TPI was associated with improved survival outcomes in patients with metastatic colorectal cancer, including those previously treated with bevacizumab. These findings support the clinical utility of FTD/TPI plus bevacizumab as an effective later-line treatment option. Further studies are warranted to clarify optimal treatment sequencing strategies.
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  • Molecular Profiling of Archival Tonsillar Squamous Cell Carcinoma in a Korean Pre-HPV-vaccination Cohort.
    1 week ago
    Tonsillar squamous cell carcinoma (TSCC) is a biologically heterogeneous malignancy in which human papillomavirus (HPV) infection, epidermal growth factor receptor (EGFR) alteration, and chromosomal instability represent major oncogenic mechanisms. This study evaluated HPV genotyping, EGFR mutation, and loss of heterozygosity (LOH) at chromosomal loci 17p13 and 9q22 in archival TSCC using conventional polymerase chain reaction (PCR)-based methodologies reproducible without next-generation sequencing infrastructure. The cohort, collected between 2000 and 2006 prior to the implementation of national HPV vaccination programs in Korea, represents a rare pre-vaccination molecular reference dataset from an East Asian population.

    Forty cases of TSCC diagnosed between 2000 and 2006 were analyzed. HPV genotyping was performed using type-specific PCR covering 21 HPV genotypes. LOH analysis was conducted using microsatellite markers targeting 17p13 and 9q22. EGFR mutations in exons 18-21 were assessed by Sanger sequencing. Associations among molecular alterations and clinicopathological parameters were analyzed using chi-squared testing.

    HPV positivity was identified in 18 out of 40 cases (45.0%). HPV-16 and HPV-18 were the predominant genotypes, accounting for 76.2% of all detected HPV genotype identifications. LOH was detected in 57.5% of cases at 17p13 and 45.0% at 9q22. EGFR mutations were identified in 17.5% of tumors. No significant associations were observed among HPV status, EGFR mutation, LOH events, or TNM stage. Notably, EGFR mutations were also observed in a subset of HPV-positive tumors, suggesting partially independent oncogenic pathways.

    This archival Korean TSCC cohort demonstrates molecular heterogeneity involving HPV-associated carcinogenesis, EGFR-mediated signaling, and chromosomal instability. The findings provide a rare pre-vaccination molecular baseline from an East Asian population and demonstrate the feasibility of integrated PCR-based molecular profiling in settings without advanced genomic infrastructure.
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  • Robot-assisted Radical Nephrectomy for Renal Cell Carcinoma With Versus Without Venous Tumor Thrombus.
    1 week ago
    Robot-assisted radical nephrectomy (RARN) for renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is technically demanding and direct comparisons with non-VTT cases in robotic cohorts are limited. We compared the perioperative and pathological outcomes of RARN between patients with and without VTT.

    We retrospectively evaluated patients who underwent RARN for RCC at a single institution between April 2022 and August, 2025. The patients were divided into VTT and non-VTT groups. Baseline characteristics, perioperative outcomes, pathological findings, and postoperative complications were compared between the groups. Multivariate logistic regression analysis was performed to assess the factors associated with postoperative complications.

    A total of 131 patients were included (30 with VTT and 101 without VTT). Patients in the VTT group had significantly larger tumors and more advanced clinical stages. The operative time tended to be longer, and the estimated blood loss was significantly higher in the VTT group; however, no patient in either group required perioperative blood transfusion. The length of hospital-stay and postoperative complication rates did not differ between groups. Pathological T stage was more advanced in the VTT group. In the multivariate analysis, VTT status was not independently associated with postoperative complications.

    Although patients with VTT had more advanced disease and required more technically demanding procedures, RARN was associated with comparable perioperative outcomes in the selected cohort. These findings support the feasibility and perioperative safety of RARN in carefully selected patients with RCC with limited VTT.
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  • From Genomic Insight to Clinical Impact: Dramatic Response in RET Fusion-positive Pancreatic Cancer.
    1 week ago
    Pancreatic cancer remains one of the deadliest solid malignancies despite advances in systemic treatment. Outcomes with current therapies remain modest, with a 5-year overall survival rate of no more than 20%. Although rare, oncogenic RET fusions represent a clinically actionable alteration and may predict substantial benefit from selective RET inhibition.

    A 48-year-old woman with pancreatic ductal adenocarcinoma developed liver metastases after first-line modified FOLFIRINOX. Comprehensive genomic profiling of the initial biopsy identified an NCOA4-RET fusion involving NCOA4 exon 6 and RET exon 12. Selpercatinib was initiated through a compassionate-use program at 160 mg twice daily. After approximately three months, the patient achieved a reduction of more than 50% in the sum of target-lesion diameters according to RECIST version 1.1. The response was sustained for more than 12 months despite dose reduction for persistent grade 2 hypertransaminasemia. The most recent assessment showed continued regression, including complete disappearance of some liver metastases. The patient remains clinically well, with an ECOG performance status of 0 and ongoing treatment.

    This case demonstrates the potential for durable and clinically meaningful responses to RET-targeted therapy in RET fusion-positive pancreatic cancer. It also supports the use of comprehensive genomic profiling to identify rare but actionable molecular alterations in patients with advanced pancreatic cancer.
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  • Interleukin-4 Genetic Polymorphisms Predict Susceptibility to Childhood Acute Lymphoblastic Leukemia.
    1 week ago
    Interleukin-4 (IL-4) is a key T-helper 2 cytokine involved in immune regulation, allergic responses, and hematological malignancies. Although aberrant IL-4 expression has been implicated in acute lymphoblastic leukemia (ALL), the contribution of IL-4 genetic polymorphisms to childhood ALL susceptibility has never been investigated. This study investigated the associations of IL-4 rs2243248 (T-1099G), rs2243250 (T-589C), and rs2070874 (T-33C) genotypes with childhood ALL risk in a Taiwanese population.

    The study was conducted at China Medical University Hospital (Taichung, Taiwan), involving 266 children diagnosed with ALL and 266 age- and sex-matched cancer-free controls. Genotypes of IL-4 rs2243248, rs2243250, and rs2070874 were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Odds ratios (ORs) and 95% confidence intervals (CIs) in addition to chi-square tests were utilized to evaluate the potential association.

    The genotypic distributions of all three IL-4 polymorphisms in controls conformed to Hardy-Weinberg equilibrium (all p>0.05). For rs2243248, neither the GT genotype (OR=1.18, 95%CI=0.73-1.92, p=0.5836) nor the GG genotype (OR=2.07, 95%CI=0.51-8.39, p=0.3341) was significantly associated with childhood ALL susceptibility. Similarly, rs2243250 CT (OR=1.18, 95%CI=0.82-1.71, p=0.4324) and CC genotypes (OR=1.93, 95%CI=0.83-4.49, p=0.1790) showed no significant effects. For rs2070874, both CT (OR=0.92, 95%CI=0.64-1.33, p=0.7294) and CC genotypes (OR=0.83, 95%CI=0.37-1.84, p=0.7936) were unrelated to ALL risk. Allelic analyses yielded consistent findings, with no significant associations observed for rs2243248 (OR=1.29, 95%CI=0.84-1.97, p=0.2823), rs2243250 (OR=1.27, 95%CI=0.95-1.72, p=0.1294), or rs2070874 (OR=0.91, 95%CI=0.68-1.23, p=0.5962).

    This first investigation of IL-4 genetic polymorphisms in childhood ALL demonstrated that rs2243248, rs2243250, and rs2070874 are not significantly associated with childhood ALL susceptibility in Taiwanese individuals. These findings suggest that common IL-4 promoter variants are unlikely to be major genetic determinants of childhood ALL risk, although larger studies in diverse populations are warranted to validate these observations.
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  • Impact of Resection Margin Width on Local Control and Prognostic Factors in HER2-enriched and Triple-negative Breast Cancer in the Modern Systemic Treatment Era.
    1 week ago
    The optimal management of close resection margins after breast-conserving surgery (BCS) remains controversial, particularly in hormone receptor-negative (HR-) breast cancer, which has a relatively high risk of local recurrence (LR). This study evaluated the association between resection margin width and LR and identified high-risk factors among patients with close margins.

    We retrospectively reviewed 842 patients with HR- breast cancer who underwent BCS followed by adjuvant radiotherapy between 2010 and 2020. Resection margins were categorized as clear (≥2 mm) or close (<2 mm). The cumulative incidence of LR was analyzed using competing-risk methods, and disease-free survival (DFS) was also evaluated.

    The 10-year cumulative incidences of LR were 4.5% in patients with clear margins and 4.9% in those with close margins, with no significant difference between the groups (p=0.359). In contrast, the 10-year disease-free survival was significantly lower in patients with close margins than in those with clear margins (87.7% vs. 92.2%; p=0.008), and close margins remained independently associated with worse DFS in multivariable analysis (hazard ratio=1.85, 95% confidence interval=1.13-3.05; p=0.015). In the multivariable analysis of patients with close margins who were treated with a tumor bed boost of 0 to 10 Gy, the presence of an extensive intraductal component (p<0.001), a Ki-67 proliferation index ≥15% (p=0.012), and the omission of HER2-targeted therapy or chemotherapy (p=0.010) were significantly associated with an increased cumulative incidence of LR.

    Close margins were not associated with a significantly increased risk of LR in patients with HR- breast cancer treated with contemporary adjuvant therapy, although they were associated with worse DFS. Patients with close margins and additional adverse factors may represent a subgroup in whom intensified local treatment, including a higher tumor bed boost dose, warrants further investigation.
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  • Multidisciplinary Treatment With Repeated Thermal Ablation for Multisite Metastatic Colon Cancer in an Elderly Patient.
    1 week ago
    Patients with stage IV colorectal cancer and multiple distant metastases are generally treated with systemic chemotherapy. However, treatment options may be limited in elderly patients with severe comorbidities or poor performance status. We report a case of long-term disease-free survival after repeated thermal ablation for metastatic colon cancer in an elderly patient who became unfit for further chemotherapy and conventional surgery.

    An 81-year-old woman with a history of myocardial infarction and cerebral infarction, who was receiving antithrombotic therapy, was diagnosed with cecal colon cancer with lymph node metastases, six liver metastases, and a giant ovarian metastasis. The tumor was RAS-mutant, BRAF-wild-type, and microsatellite stable. She received three courses of bevacizumab plus capecitabine and oxaliplatin, resulting in stable disease. She subsequently underwent right hemicolectomy, right oophorectomy, left lateral sectionectomy of the liver, and microwave ablation for two liver metastases. Approximately one month after surgery, recurrent cerebral infarction occurred, and her performance status deteriorated from 1 to 3. She declined further chemotherapy and major surgery. Three recurrent liver metastases and one lung metastasis were subsequently treated with percutaneous thermal ablation. Five years after treatment initiation and three years after the final local treatment, she remains alive without disease.

    This case illustrates that repeated thermal ablation may provide durable local disease control in carefully selected patients with metastatic colon cancer who are unfit for further chemotherapy or invasive surgery.
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  • Clinical Outcomes and Prognostic Factors of ABCP Therapy in EGFR-mutated NSCLC in the Osimertinib Era.
    1 week ago
    Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) therapy has demonstrated efficacy in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after EGFR-tyrosine kinase inhibitor (TKI) failure. However, real-world evidence in the osimertinib era remains limited. This study aimed to evaluate the efficacy, safety, and prognostic factors of ABCP therapy in patients with EGFR-mutated NSCLC.

    This retrospective study evaluated patients with EGFR-mutated NSCLC who received ABCP therapy after EGFR-TKI failure at two institutions between January 1, 2019 and March 31, 2025. Progression-free survival (PFS), overall survival (OS), treatment response, and safety were evaluated, and prognostic factors were identified.

    Sixty-one patients were evaluated. The median PFS and OS were 6.9 months [95% confidence interval (CI)=4.7-8.2] and 20.2 months (95% CI=12.9-25.5), respectively. The objective response rate was 59.0%. Stage IVB disease [hazard ratio (HR)=2.41, p=0.004] and Eastern Cooperative Oncology Group performance status (ECOG PS) score ≥2 (HR=5.10, p=0.007) were significantly associated with shorter PFS. Stage IVB disease (HR=2.29, p=0.014), ECOG PS score ≥2 (HR=15.06, p<0.001), and liver metastasis (HR=3.21, p=0.007) were significantly associated with shorter OS. Stage IVB disease and ECOG PS score ≥2 were independent prognostic factors for both PFS and OS. Prior osimertinib treatment was not significantly associated with either PFS or OS. No unexpected safety signals were observed.

    ABCP therapy was associated with a median PFS of 6.9 months and median OS of 20.2 months, with no unexpected safety signals in patients with EGFR-mutated NSCLC after EGFR-TKI failure. Stage IVB disease and poor ECOG PS are independent prognostic factors for survival, whereas prior osimertinib treatment is not significantly associated with survival outcomes. Overall, stage IVB disease and poor ECOG PS were associated with survival outcomes, whereas prior osimertinib exposure was not significantly associated with PFS or OS in this cohort.
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  • CTDNEP1 Expression Is Associated With Subtype-dependent Prognostic Patterns in Renal Cell Carcinoma.
    1 week ago
    Renal cell carcinoma (RCC) comprises multiple histological subtypes, such as kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP), each with distinct molecular characteristics. Identifying novel genes involved in the onset and progression of these subtypes is crucial for the development of more effective treatments. This study investigates the role of CTD nuclear envelope phosphatase 1 (CTDNEP1), a phosphatase-encoding gene, in KIRC and KIRP using multi-omics data from The Cancer Genome Atlas (TCGA).

    We analyzed CTDNEP1 expression in KIRC and KIRP using TCGA and Pan-Cancer Atlas datasets. Kaplan-Meier survival and Cox proportional hazard analyses were performed to evaluate the association between CTDNEP1 expression and patient prognosis. We explored biological processes associated with CTDNEP1 expression using GO and KEGG pathway enrichment analyses. Finally, we examined the relationship between CTDNEP1 expression and the tumor immune microenvironment using immune infiltration analysis.

    CTDNEP1 expression was significantly higher in KIRC and KIRP tissues compared to normal tissues, especially in early-stage tumors. Prognostic impact in KIRP was limited and inconsistent, whereas in KIRC, high CTDNEP1 expression correlated with significantly poorer patient prognosis, particularly in Stage III. Functional enrichment analysis revealed associations with immune-related pathways in KIRC, whereas in KIRP, associations were observed with pathways involved in the PI3K-Akt, MAPK, and TGF-β signaling pathways. In the immune infiltration analysis, CTDNEP1 expression showed only weak correlation with immune cell infiltration.

    CTDNEP1 expression was associated with subtype-dependent prognostic patterns in RCC. In particular, high CTDNEP1 expression was associated with adverse survival outcomes in KIRC. These findings suggest that CTDNEP1 may serve as a candidate prognostic biomarker in RCC. Further experimental studies are required to clarify whether CTDNEP1 directly contributes to RCC progression.
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  • First-trimester pregnancy-associated breast cancer managed without pregnancy termination: a report with long-term follow-up.
    1 week ago
    Pregnancy-associated breast cancer (PABC) presents unique challenges requiring a multidisciplinary approach to balance maternal treatment efficacy with fetal safety. This case describes a first-trimester breast cancer diagnosis, managed with a total mastectomy and axillary lymph node dissection, followed by a specialised adjuvant chemotherapy plan. Chemotherapy was initiated after the first trimester, with additional chemotherapy administered post partum. Although the National Comprehensive Cancer Network guidelines suggest considering early termination for first-trimester PABC, the patient opted to continue the pregnancy. A multidisciplinary team carefully planned the treatment sequence to minimise fetal risks while ensuring oncologic efficacy, considering the patient's concerns. A 9-year follow-up demonstrated no cancer recurrence and normal child development. This case underscores the importance of individualised treatment strategies in PABC, considering maternal prognosis, gestational age, treatment timing and patient preferences. With a multidisciplinary and patient-centred approach, pregnancy can safely continue alongside cancer treatment, achieving positive outcomes.
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