The combination of chemotherapy and nivolumab has become the standard first-line therapy for advanced gastric cancer (AGC) following the results of the CheckMate 649 and ATTRACTION-4 trials. Claudin18.2 (CLDN18.2) and trophoblast cell surface antigen 2 (TROP2) have recently emerged as potential therapeutic targets in AGC. However, their association with the efficacy of nivolumab is not known. The aim of this study was to clarify the efficacy of nivolumab according to CLDN18.2 and TROP2 expression in AGC.

This retrospective study included patients with AGC who had received systemic chemotherapy, with the primary objective of evaluating clinical outcomes in patients treated with nivolumab monotherapy after third-line therapy, by CLDN18.2 and TROP2 expression. The endpoints were overall survival after starting systemic chemotherapy and progression-free survival and overall survival after starting nivolumab monotherapy after third line treatment (Nivo-PFS and Nivo-OS, respectively).

The primary analysis included 69 patients treated with nivolumab monotherapy out of the 121 patients selected from the database. No significant difference in Nivo-PFS or Nivo-OS was found between the CLDN18.2-positive and CLDN18.2-negative populations or between the TROP2-positive and TROP2-negative populations. In the CLDN18.2-positive population, multivariable analysis showed that combined positive score (CPS) ≥1 was associated with significantly longer OS, Nivo-PFS, and Nivo-OS (p=0.03, p=0.03, p<0.01, respectively). In the TROP2-positive population, CPS ≥1 showed a tendency toward better prognosis for Nivo-OS (p=0.31) in the multivariable analysis.

Among patients undergoing nivolumab treatment, CPS ≥1 was significantly associated with longer survival outcomes in CLDN18.2-positive patients, and a tendency toward improved Nivo-OS in TROP2-positive patients.

Colorectal cancer (CRC) remains a major global health challenge with poor survival in advanced disease. Identifying new oncogenic drivers is essential for improving diagnosis and therapy. This study investigated the oncogenic role of nucleophosmin 1 (NPM1) in CRC and its involvement in the AKT/mTOR signaling pathway.

TCGA-COAD datasets were analyzed to compare NPM1 expression in tumor and normal tissues. Functional assays (MTT proliferation, soft agar colony formation, migration, and in vivo xenograft models) were performed after siRNA-mediated NPM1 knockdown in HCT-116 and DLD-1 cells. Western blotting and phospho-kinase arrays were used to evaluate phosphorylation of AKT, mTOR, and p70 S6 kinase.

NPM1 expression was significantly upregulated in CRC tissues. Knockdown of NPM1 suppressed proliferation, migration, anchorage-independent growth, and in vivo tumorigenicity. Mechanistically, NPM1 depletion reduced phosphorylation of AKT, mTOR, and p70 S6 kinase, while total protein levels were unchanged. Downstream oncogenic regulators, including MYC and AP-1 components (c-Jun and c-FOS), were also decreased.

NPM1 acts as an oncogenic driver in colorectal cancer by activating the AKT/mTOR signaling pathway. Elevated NPM1 expression highlights its potential as a diagnostic, prognostic, and therapeutic biomarker in CRC.

Pathologic stage II non-small cell lung cancer (NSCLC) exhibits heterogeneous outcomes despite curative resection. Although adjuvant EGFR-TKI and immunotherapy have improved survival in resected NSCLC, subgroup analyses from major trials show only modest benefit in stage II disease. Given these limited gains and the variable cost-effectiveness of adjuvant therapy across regions, identifying prognostic factors is essential to guide treatment decisions and support value-based precision care.

We retrospectively analyzed 115 patients with pathologic stage II NSCLC (27 IIA, 88 IIB) who underwent complete resection at a tertiary hospital in Taiwan (2016-2023). Clinicopathologic variables-including histologic subtype, spread through air spaces (STAS), and lymphovascular invasion (LVI) - were reviewed. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using Kaplan-Meier and Cox proportional hazards analyses.

The 5-year RFS and OS rates were 50.9% and 67.9%, respectively. Independent predictors of recurrence included tumor size >4 cm [hazard ratio (HR)=2.88, p=0.008], N1 nodal status (HR=3.20, p=0.016), and high-risk adenocarcinoma subtype (micropapillary/solid; HR=2.80, p=0.014). Adjuvant chemotherapy significantly improved OS (76.4% vs. 37.2%, p=0.002).

Tumor size, nodal involvement, and histologic subtype are key prognostic determinants in stage II NSCLC. Identifying high-risk patients is crucial to optimize selection for adjuvant immunotherapy or targeted therapy and to ensure clinical and economic benefit.

Extrapancreatic invasion (EPI) is a well-known adverse prognostic factor in pancreatic cancer; however, whether the absence of EPI defines a distinct clinical entity remains unclear. This study aimed to clarify the clinicopathological features and prognosis of pancreatic ductal adenocarcinoma (PDAC) confined within the pancreas.

A total of 199 patients who underwent curative-intent pancreatectomy for PDAC between 2012 and 2022 were retrospectively analyzed. Patients were classified into EPI-negative (n=19) and EPI-positive (n=180) groups. Clinicopathological characteristics, recurrence-free survival (RFS), and overall survival (OS) were compared between the two groups.

EPI-positive tumors were significantly associated with higher CA19-9 levels, larger tumor size, lymph node metastasis, and lymphovascular/perineural invasion. None of the EPI-negative patients experienced recurrence within 3 years or disease-specific death within 5 years. Multivariate analysis identified the absence of EPI as an independent favorable prognostic factor for both RFS and OS.

PDAC confined within the pancreas, without EPI, represents a biologically distinct subset with remarkably favorable outcomes. Assessing EPI status may aid in tailoring perioperative treatment strategies and preventing overtreatment in selected patients.

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.

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.

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.

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.

Metastatic breast cancer remains a major clinical challenge despite the availability of various chemotherapeutic agents. Current metabolic inhibitors have limitations, prompting the need for innovative strategies that selectively target tumor cells while sparing normal tissues. This study aimed to propose a novel approach focused on depriving tumor cells of glucose while ensuring nutrient delivery to normal cells.

A comprehensive literature review was conducted using PubMed and Google Scholar. The proposed strategy involved focusing on studies that deplete glycogen stores in normal tissues through prolonged fasting, followed by administration of total parenteral nutrition (TPN) enriched with essential ingredients encapsulated in specialized liposomes. Three liposomal strategies were outlined: 1-pH-sensitive copolymer coating: liposomes coated with polyethylene glycol-poly-L-histidine (PEG-PLH) selectively release contents in normal tissues by binding glucose transporters (GLUTs) while avoiding tumor cell GLUTs. 2-Superhydrophobic fluorinated compounds: conjugation with trastuzumab targets HER2 ligands on tumor cells, preventing liposome accumulation in tumors. 3-Superhydrophobic Zwitterionic modifications: these create a hydration layer around liposomes, preventing passage through capillary walls and reducing tumor tissue accumulation.

The strategies were designed to selectively reduce glucose availability to tumor cells while preserving normal cellular metabolism. The proposed liposomal modifications theoretically enhance targeted delivery and minimize off-target effects, providing a novel framework for metabolic therapy in metastatic breast cancer.

This novel glucose-targeted liposomal approach shows potential to improve therapeutic specificity and efficacy in metastatic breast cancer. Further in vitro, in vivo, and clinical studies are warranted to validate its effectiveness and explore applicability to other solid tumors.

Immune checkpoint inhibitor (ICI)-based regimens can be associated with prolonged survival and disease control after treatment discontinuation without further anticancer therapy. An integrated, comprehensive partitioned survival analysis describes how patients spend overall survival (OS) time both on/off treatment and with/without toxicity. Previous analysis of first-line (1L) nivolumab+ipilimumab for advanced renal cell carcinoma (aRCC) in CheckMate 214 showed treatment-free survival (TFS; time between 1L and second-line (2L) therapies) was twice as long versus sunitinib. TFS and survival states for ICI plus vascular endothelial growth factor receptor-tyrosine kinase inhibitor are of interest.

In CheckMate 9ER, 651 randomized patients with aRCC received 1L nivolumab+cabozantinib or sunitinib. Minimum follow-up was 4 years. We partitioned area under the Kaplan-Meier OS curve into three survival states defined from randomization: time on 1L protocol therapy, TFS, and survival after 2L subsequent systemic therapy initiation. TFS and protocol therapy were subdivided into mean times with/without grade 2+ treatment-related adverse events. Areas under and between Kaplan-Meier curves were estimated by 48-month restricted mean times to event. Bootstrapped 95% CIs for between-group differences are reported.

At 4 years post-randomization, Kaplan-Meier OS estimates were 49.2% versus 40.2% with nivolumab+cabozantinib and sunitinib, respectively; 17.6% versus 4.7% of patients were in TFS; 15.8% versus 8.2% remained on 1L protocol therapy. The 48-month mean time on protocol therapy for nivolumab+cabozantinib versus sunitinib was 22.6 and 14.1 months; 48-month mean TFS was 7.0 and 4.6 months (difference, 2.4 (95% CI 0.8 to 3.9)); 48-month mean survival after 2L therapy initiation was 5.5 and 12.0 months, respectively. The nivolumab+cabozantinib group spent 8.5 (95% CI 6.2 to 10.8) months more mean survival time on 1L protocol therapy, whereas the sunitinib group had 6.5 (95% CI 4.4 to 8.6) months more mean survival time after 2L therapy initiation. Both treatment groups spent at least half of TFS with grade 2+toxicity, resulting in a difference in mean TFS without toxicity of 0.7 (95% CI -0.4 to 1.8) months.

Partitioned survival analysis over 4 years after initiation of 1L therapy for aRCC indicated that longer OS with nivolumab+cabozantinib versus sunitinib involved more time on 1L therapy and in TFS, and less survival time after 2L therapy initiation.

NCT03141177.

Pathological characteristics and MMR status can be determined from microscopic indicators and immunohistochemical (IHC) staining of surgical specimens, and these approaches are more cost-effective and convenient than genome profiling tests. We aimed to evaluate the impact of MMR deficiency on survival outcomes and build a new prognostic model for early-stage endometrial carcinoma (EC) patients.

Patients with stage I to II EC who underwent hysterectomy followed by adjuvant radiotherapy from Oct. 2017 to Dec. 2020 at our institution were retrospectively reviewed. Tumor MMR status was routinely tested by IHC. According to MMR status, they were classified into intact MMR (MMRp) group and defective MMR (MMRd) group.

Patients were classified into MMRp group (n = 207) and MMRd group (n = 69). Compared with those in the MMRp group, patients in the MMRd group were more likely to have high-grade disease, LVSI, and high-intermediate risk (HIR)-to-high risk (HR) classifications. The 3-year CSS, DFS, and DMFS rates were significantly lower in the MMRd group. When patients were stratified by risk group, DFS and DMFS were significantly worse among MMRd patients in the HIR-to-HR group. Regarding failure patterns, MMRd patients were more likely to experience distant failure. Among 276 patients, multivariate Cox analysis revealed that ER or PR status, myometrial invasion (MI), MMR status, and LVSI were independent prognostic factors for DFS, whereas ER or PR status, MMR status, and MI were significant predictors of DMFS. A prediction model combining the MMR status and the significant prognostic predictors mentioned above in the multivariate analysis was built through nomogram models.

Among early-stage EC patients, MMRd group had poorer survivals. Combination of MMR status and other clinicopathological factors could establish a new prognostic model. Prospective studies with full molecular sequencing to determine the prognostic significance of MMR status are needed.

Niraparib (NIRA) is a poly(ADP-ribose) polymerase inhibitor used as maintenance therapy for ovarian carcinomas. Thrombocytopenia is a common adverse event associated with NIRA. This study aimed to evaluate the frequency of NIRA-induced thrombocytopenia and the associated risk factors in clinical practice.

Data from 30 patients who received NIRA as a first-line or recurrent treatment at our institution were retrospectively analyzed to assess reductions in platelet count (PLT).

The median participant age was 59 (range: 39-75) years, and the median weight was 50 (range: 36-80) kg. NIRA was initiated at a median of 4 (range: 3-8) weeks after the last chemotherapy dose. The prevalence of grade ≥3 thrombocytopenia was 23.3 %, dose interruptions occurred in 53.3 % and dose reductions occurred in 40 %. The median follow-up time was 20 (range: 2-166) months after resumption. Due to thrombocytopenia, one patient discontinued treatment 2 weeks after administration (nadir PLT: 1 × 10⁹/L), and 2 others discontinued treatment after resumption. For the non-interruption and interruption groups, the median nadir PLTs were 194 (91-318) and 57 (1-89) × 10⁹/L (p < 0.001), respectively, the median baseline PLTs were 215 vs. 120 × 10⁹/L (p < 0.001), respectively, and the nadir PLTs during prior chemotherapy were 175 vs. 73 × 10⁹/L (p = 0.007), respectively. Lower baseline PLTs were significantly associated with an increased risk of thrombocytopenia (OR 0.793, 95 % CI 0.654-0.964; p = 0.019).

Our real-world data reaffirmed that thrombocytopenia is a significant adverse event that affects the continuation of NIRA and requires careful monitoring. Adjusting the start time to ensure an adequate baseline PLT may help mitigate this risk, but larger-scale studies are needed to validate these findings.

The methods of laparoscopic staging surgery (LSS) for endometrial cancer can generally be classified into two approaches: laparoscopic-assisted vaginal hysterectomy (LAVH)-based LSS and total laparoscopic hysterectomy (TLH)-based LSS. This study aims to compare perioperative and oncologic outcomes between LAVH-based LSS and TLH-based LSS.

Between January 2019 to December 2024, 118 patients who underwent laparoscopic staging surgery were retrospectively observed. Patient characteristics, such as age, BMI, parity, disease extension, histology subtypes, estimated blood loss, operative time, complications and recurrence were collected and analyzed.

TLH was associated with significantly lower estimated blood loss compared with LAVH (119.0 ± 69.9 vs. 218.5 ± 375.1 mL, p = 0.036). TLH also offered a tendency of shorter operative time but without significance (197.40 ± 50.74 vs. 214.41 ± 66.89 min, p = 0.135). While hospital stay, complication rate, and 30-day re-hospitalization were comparable between groups. Four recurrences were observed, all in the LAVH group. Kaplan-Meier analysis showed no significant difference in progression-free survival (p = 0.300).

TLH-based LSS in early-stage EC appears a safe approach, offering reduced blood loss without compromising perioperative or oncologic outcomes compared with LAVH-based LSS.