Anticancer research最新文献

Background/aim: NF2-related schwannomatosis is a rare hereditary tumor predisposition syndrome, formerly known as Neurofibromatosis type 2 (NF2), and is characterized by the development of multiple schwannomas. The hallmark manifestation is the occurrence of bilateral vestibular schwannomas (VSs). Disease progression and clinical outcomes vary widely among patients, and conventional magnetic resonance imaging (MRI) metrics-such as tumor size-do not fully account for these differences. Radiomic analysis offers a quantitative approach to extract advanced imaging biomarkers that may capture tumor microstructure and growth behavior more accurately, potentially improving prognostication and individualized management in NF2.

Patients and methods: A retrospective cohort of 32 patients with NF2 was analyzed, comprising 170 cranial MRI scans of 232 VSs (112 left, 120 right) acquired at different time points over the course of disease, with previously treated tumors excluded. Tumor growth was quantified as absolute and percentage growth rates per month. Radiomic features were extracted from segmented tumors and correlated with Common Terminology Criteria for Adverse Events (CTCAE) graded clinical findings. Hearing impairment was graded based on subjective function due to limited audiometric data.

Results: In this exploratory analysis, no Spearman |ρ| >0.40 correlations were observed between radiomics features and tumor growth rates, nor among clinical parameters (excluding depression and anxiety). Right-sided tumors were associated with significantly greater hearing impairment compared to left-sided tumors despite comparable volumes (p=0.030). Age-stratified analyses revealed distinct patterns: in younger patients (<30 years), fast-growing tumors displayed more homogeneous texture profiles, while in older patients (>30 years), rapid growth was linked to greater heterogeneity.

Conclusion: Radiomic profiling indicates that both tumor laterality and patient age influence the relationship between imaging features and clinical outcomes in NF2-associated VS. Homogeneity was linked to aggressive growth in younger patients, heterogeneity characterized progression in older patients. These findings suggest that radiomic biomarkers may complement volumetric measures and support individualized monitoring and treatment strategies in NF2.

Background/aim: T-cell priming within tumor-draining lymph nodes (TDLNs) is essential for optimal immune checkpoint inhibitor (ICI) activity. Because neck dissection (ND) removes cervical lymph nodes that may function as TDLNs in head and neck cancer (HNC), its impact on subsequent ICI efficacy remains clinically relevant. This study investigated whether prior ND influences treatment outcomes with nivolumab in recurrent or metastatic HNC.

Patients and methods: Fifty-four patients with recurrent or metastatic HNC treated with nivolumab between 2017 and 2025 were retrospectively analyzed. Patients were stratified into locoregional disease (LRD; n=41) and distant metastasis (DM; n=13) cohorts. Within each cohort, outcomes were compared between patients with and without prior ND.

Results: In the LRD cohort (n=41), the median progression-free survival was 2.3 vs. 4.0 months (p=0.089) and median overall survival was 9.8 vs. 18.8 months (p=0.044) for the ND and non-ND groups, respectively. In the DM cohort (n=13), outcomes were unaffected by ND. Multivariate analysis showed a non-significant trend toward worse outcomes in the ND group.

Conclusion: Prior ND was associated with inferior survival in LRD but not in DM-only disease, suggesting that an ND-related loss of TDLN function reduces ICI efficacy.

Background/aim: Human epidermal growth factor receptor 2 (HER2) status assessment is subdivided according to trastuzumab-deruxtecan (T-DXd) suitability, and there is a discrepancy in HER2 staining depending on reagents. This study investigated HER2 status by HercepTest and PATHWAY 4B5 immunohistochemical assays in breast cancer.

Patients and methods: We reviewed the HER2 test data for breast cancer from the institutional pathology database between January 2020 and December 2024. The HercepTest was used in the early period (January 2020 to April 2023), and 4B5 was used in the late period (May 2023 to December 2024). The HER2 status of 2,328 breast cancer tissues (2,313 fresh and 15 archived tissues) was analyzed.

Results: The HER2 statuses by HercepTest and 4B5 in fresh samples were as follows: positive 9.5% and 8.6%, low 59.5% and 48.5%, ultralow 18.2% and 21.8%, and zero 12.9% and 21.1%, respectively. Eight (53.3%) archived samples from the same cases had changed HER2 status (1 upgraded and 7 downgraded).

Conclusion: HER2 staining was lower in 4B5 testing than in the HercepTest. Companion diagnosis using 4B5 is required to determine indications for T-DXd, especially for HER2-ultralow evaluations.

Background/aim: The introduction of the HER2-low concept has redefined the biological spectrum of breast cancer. However, the clinicopathological and prognostic significance of HER2 expression in ductal carcinoma in situ (DCIS) remains unclear. This study aimed to reassess HER2 expression in DCIS using the HER2-low classification.

Patients and methods: A total of 221 patients who underwent surgery and were pathologically diagnosed with DCIS at Osaka Metropolitan University hospital between June 2007 and December 2023 were retrospectively analyzed. HER2 expression was assessed using immunohistochemistry (IHC) and classified as HER2-0, HER2-low (IHC 1-2+), or HER2-high (IHC 3+). Clinicopathological features were compared among groups, and disease-free survival (DFS) and recurrence-free interval (RFI) were evaluated using Kaplan-Meier and Cox regression analyses.

Results: HER2-0, HER2-low, and HER2-high were observed in 96 (43.4%), 80 (36.2%), and 45 (20.4%) patients, respectively. HER2 expression correlated significantly with estrogen receptor (p=0.011), progesterone receptor (p<0.001), comedonecrosis (p=0.030), calcification (p=0.019), and nuclear grade (p=0.006). Although no significant differences were found among the three groups, the HER2-0 subgroup tended to show longer RFI compared with HER2-positive cases (p=0.051). Multivariate analysis identified tumor size as an independent prognostic factor for DFS (hazard ratio=34.47, p=0.004).

Conclusion: HER2 expression redefined by the HER2-low concept reflects the biological diversity of DCIS. Evaluation of HER2 status as a continuous spectrum may aid in risk stratification and contribute to understanding early HER2-driven tumor evolution.

Background/aim: Myxofibrosarcomas (MFS) are highly infiltrative soft tissue sarcomas that most commonly occur in adults within the sixth to seventh decades. Diagnosis relies on histopathological analysis as no definitive molecular markers have been identified. This study seeks to describe the mutational landscape of MFS, characterize mutations unique to certain populations, and identify mutations that may be of particular utility in diagnosis and treatment.

Patients and methods: Using the AACR Project GENIE database, we identified a cohort of 202 patients with MFS. Patients were stratified by sex, age, race, and ethnicity. Tumors were categorized as primary, metastatic, locally recurrent, or distant organ metastases. Somatic mutations and copy number alterations were identified. Data were analyzed using R and RStudio, with p<0.05 denoting statistical significance.

Results: We are the first to link the following mutations to MFS: NOTCH3, ALOX12B, SDHA, ETV6, NCOA2 and SOS2. The most common somatic mutations included TP53 (27.98%), ATRX (14.68%), NF1 (9.17%), and RB1 (7.80%). Homozygous deletions were most frequent in TP53 (28.7%), CDKN2A (20.5%), CDKN2B (19.48%), and RB1 (15.38%), while amplifications were most frequent in NCOR1 (6.29%) and FLCN (5.13%). Several mutations frequently co-occurred, while NF1 and RB1 demonstrated total mutual exclusivity. NCOA2 mutations were exclusive to White patients and NKX2-1 to non-White patients. Mutations in MAP2K4 and ALOX12B were unique to males, while SDHA mutations were unique to females.

Conclusion: As we enter the era of precision medicine, classifying cancers by molecular markers will become increasingly valuable. Our investigation enriches the literature by identifying novel mutations and mutations exclusive to certain demographic groups. These findings support a shift beyond histology toward molecularly informed diagnostics and pathway-directed therapeutic hypotheses for MFS. Next steps should validate candidate markers in independent cohorts and link genomic profiles to clinicopathologic features, disease course, and treatment response to improve clinical translation. These observations will help shape diagnostics and targeted therapies against MFS.

Background/aim: Human epidermal growth factor receptor 2 (HER2) over-expression occurs in approximately 10-20% of gastric cancers. While HER2-positive tumors tend to behave more aggressively, anti-HER2 therapy has markedly improved outcomes in this subgroup. Trastuzumab (Tmab) and trastuzumab deruxtecan (T-DXd) are key agents, yet real-world data on how these treatments are delivered and tolerated remain scarce.

Patients and methods: We retrospectively reviewed 43 patients with advanced or recurrent HER2-positive gastric or gastroesophageal junction cancer who received chemotherapy between 2014 and 2025. Clinical features, laboratory data, and treatment courses were extracted from medical records. Overall survival (OS) was analyzed using Kaplan-Meier methods and prognostic factors using Cox regression.

Results: The median age was 70 years, and 81% of tumors were HER2 immunohistochemistry (IHC) 3+. Median OS was 29.6 months, with 3- and 5-year survival rates of 36% and 29%, respectively. Longer OS was linked with HER2 3+ status, gastrectomy, single metastatic site, normal lactate dehydrogenase (LDH), low neutrophil-to-lymphocyte ratio, and lower modified Glasgow Prognostic Score (mGPS). Patients maintaining anti-HER2 therapy ≥260 days lived significantly longer than those treated for a shorter duration (p<0.001). On multivariate analysis, elevated LDH, mGPS=2, and short anti-HER2 exposure independently predicted poorer survival.

Conclusion: Sustained anti-HER2 therapy was strongly associated with longer survival. Adjusting the cytotoxic partner to manage toxicity may help patients continue trastuzumab-based treatment and achieve better outcomes.

Background/aim: Methionine addiction is a fundamental and general hallmark of cancer termed the Hoffman effect. Methionine restriction using recombinant methioninase (rMETase) has shown synergistic efficacy with numerous types of chemotherapeutic agents against cancer cells and not normal cells. Methionine adenosyltransferase 2A (MAT2A) is a crucial enzyme converting methionine to S-adenosylmethionine (SAM). A MAT2A inhibitor, AG-270, has been proposed as a potential anti-cancer drug. The present study evaluated whether AG-270 is a cancer-specific agent by comparing its efficacy in combination with rMETase on cancer and normal cells.

Materials and methods: The half-maximal inhibitory concentrations (IC₅₀) of rMETase and AG-270 were determined on HCT116 human colon-cancer cells and Hs-27 human normal fibroblasts in vitro. The efficacy of rMETase combined with AG-270, at their respective IC₅₀ values, on HCT116 and Hs-27 was also determined. Cell viability was evaluated using the WST-8 reagent.

Results: The IC₅₀ values of rMETase were 0.35 U/ml for HCT116 and 1.14 U/ml for Hs-27. The IC₅₀ values of AG-270 were 4.38 μM for HCT116 and 6.55 μM for Hs-27. The combination of rMETase and AG-270, at their respective IC₅₀, had synergistic efficacy on both cancer and normal cells, reducing viability to approximately 20% in both cell lines (p<0.05).

Conclusion: AG-270 showed lack of cancer specificity in combination with rMETase when tested on both cancer and normal cells. The present results contrast with numerous chemotherapy agents, which in combination with rMETase are synergistic on cancer cells but not on normal cells. The present findings suggest that MAT2A inhibition affects crucial metabolic pathways in normal as well as cancer cell types and thus AG-270 may not be suitable as a cancer-specific therapeutic strategy.

Background/aim: Fluorescence ureteral navigation (FUN) using near-infrared devices (e.g., NIRC™ and IRIS) can assist in the visualization of ureters and the prevention of iatrogenic injury during complex colorectal procedures. However, its adoption in Japan remains limited.

Patients and methods: A nationwide anonymous web-based survey was conducted among surgeons in Japan from May 1 to June 30, 2025 to assess awareness, usage, and barriers related to FUN. A total of 124 valid responses were collected.

Results: The majority of the respondents specialized in lower gastrointestinal surgery (66.1%), and 63.7% had more than 11 years of clinical experience. Among the respondents, 74.2% were aware of FUN, but only 25.8% had used it. Notably, 96.0% of respondents felt that there were cases in which they would like to use FUN, and 89.5% perceived FUN as educationally valuable for junior surgeons. The most desired indications included locally advanced rectal or sigmoid cancer (84.7%), recurrent cancer (77.4%), and diverticulitis (59.7%). Among respondents who were aware of FUN, 42.9% reported having encountered cases for which they wanted to use FUN but could not. The main barriers included difficulty coordinating with urologists (53.8%), high device cost (28.2%), and a lack of compatible fluorescence imaging systems (23.1%). Psychological concerns, such as hesitancy due to the perceived burden on urology departments (51.6%) and scheduling complexity (42.7%), were also notable. Only 7.3% of surgeons had experience inserting ureteral catheters, although 35.5% had assisted with the procedure.

Conclusion: This nationwide survey highlights the strong clinical and educational demand for FUN among Japanese surgeons as well as persistent logistical and institutional barriers. Facilitating surgeon-led implementation through improved access to devices, structured training, and interdisciplinary collaboration may support broader clinical adoption.

Background/aim: Postoperative severe complications (PSC) are key indicators of surgical quality because they increase healthcare costs, delay adjuvant chemotherapy, and impair long-term survival. Hepato-biliary-pancreatic surgeons perform both liver and pancreatic procedures, which differ substantially in technical complexity; therefore, identifying field-specific risk factors for complications is essential. This study aimed to determine perioperative predictors of PSC following major liver and pancreatic surgery.

Patients and methods: This single-center retrospective study included 675 patients who underwent major liver or pancreatic surgery between January 2010 and December 2023 at Gifu University Hospital, Japan. Perioperative variables were analyzed in 328 patients, consisting of those with PSC (n=167; liver n=49, pancreas n=118; Clavien-Dindo ≥III) and those without PSC (n=161; liver n=53, pancreas n=108; Clavien-Dindo

Results: In major pancreatic surgery, PSC were significantly associated with male sex (p=0.01), higher body mass index (p=0.03), smoking history (p=0.02), prior malignancy (p=0.02), respiratory comorbidity (p=0.04), and elevated C-reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) on postoperative day (POD) 3 (p<0.001, p<0.01, and p<0.01). Multivariate analysis identified CAR on POD3 (>5.0) as the sole independent predictor [odds ratio (OR)=4.27; 95% confidence interval (CI)=2.05-9.13; p<0.001]. In major liver surgery, PSC were associated with abnormal CONUT score (p=0.04) and cardiac comorbidity (p=0.04) in univariate analysis, whereas multivariate analysis demonstrated abnormal CONUT score as the only independent predictor (OR=3.40; 95%CI=1.37-8.81; p<0.01).

Conclusion: Postoperative inflammatory markers, particularly CAR on POD3, may function as early indicators of complication severity after major pancreatectomy. Conversely, preoperative nutritional status assessed by CONUT independently predicted PSC following major hepatectomy. These results support inflammation-guided postoperative management in pancreatic surgery and highlight the importance of nutritional optimization before liver surgery.

Background/aim: Urine cyclic guanosine monophosphate (cGMP) has been proposed as a prognostic biomarker for therapy response and the risk of relapse of cervical cancer after treatment with radiotherapy (RT). In the present study, an in vitro model with cervical cancer cells (C4-1) was established to determine whether changes in extracellular cGMP levels were predictive for effects of ionization radiation (IR).

Materials and methods: During exponential growth, C4-1 cells were exposed to IR with doses between 2 and 12 Gy. The cells were harvested at intervals between one and six days.

Results: The effect of IR on cell growth and extracellular cGMP levels was dose- as well as time-dependent. Three and six days after IR, the cell fractions were reduced with identical sensitivity (ED50 of 1.9 and 1.8 Gy, respectively). The extracellular cGMP levels showed a fall from the first day to sixth day, both in control and after irradiation (2 and 4 Gy), but with somewhat higher levels after IR. However, the extracellular cGMP levels increased after 8 and 12 Gy exposure by 100% and 270%, respectively. When the data were presented as extracellular cGMP levels (% above control), a clear dose- and time-dependency were observed.

Conclusion: From a translational perspective, extracellular cGMP levels may be used to monitor effects and be a potential tool for individualization of radiation therapy (RT).