Anticancer research最新文献

Background/aim: The first-line treatment for platinum-sensitive recurrent or metastatic head and neck cancer (R/M HNSCC) is pembrolizumab with or without chemotherapy. The decision to combine chemotherapy largely depends on programmed death-ligand 1 (PD-L1) expression; however, chemotherapy is often difficult to administer in older adult patients because of reduced physiological reserve and comorbidities. Therefore, we analyzed real-world data to evaluate the effectiveness of pembrolizumab monotherapy according to age and PD-L1 combined positive score (CPS).

Patients and methods: This multicenter retrospective observational study analyzed the medical records of patients who received pembrolizumab monotherapy for R/M HNSCC. Patients with unknown CPS were excluded. This study was approved by our institutional review board. Overall survival (OS), progression-free survival (PFS), response rates, and immune-related adverse events were evaluated. All analyses were exploratory, and statistical significance was set at p<0.05.

Results: A total of 130 patients were included (median age, 72.5 years; range=40-89 years). Patients were classified into a young group (<75 years, n=75) and an older adult group (≥75 years, n=55). Median OS and PFS did not differ significantly between the young and older adult groups. Among older adult patients, those with high CPS (≥20) showed a trend toward improved OS compared with those with low CPS. Response rates and the incidence of immune-related adverse events were comparable between age groups.

Conclusion: Pembrolizumab monotherapy demonstrated clinically meaningful real-world effectiveness and acceptable tolerability in older adult patients with R/M HNSCC, particularly in those with high PD-L1 expression (CPS≥20). In contrast, the benefit appeared limited in older adult patients with low CPS, underscoring the importance of careful patient selection and timely consideration of alternative strategies in real-world practice.

Background/aim: Adrenocortical carcinoma (ACC) is an endocrine tumor arising in the adrenal cortex. Although its incidence is extremely low, it is highly malignant, rapidly proliferating, and infiltrating surrounding organs, resulting in a poor prognosis. YME1 Like 1 ATPase (YME1L1) is an ATP-dependent metalloprotease that regulates mitochondrial proteostasis. Recently, a correlation between YME1L1 expression and the prognosis of several cancers has been reported. However, no studies have examined the expression level of YME1L1 mRNA in ACC tissues or the relationship between YME1L1 expression and the prognosis of ACC patients. Therefore, there is a need to investigate the relationship between YME1L1 expression and the prognosis of ACC patients.

Materials and methods: YME1L1 mRNA expression and survival in ACC patients were analyzed using the TCGA database with the UALCAN and GEPIA platforms.

Results: YME1L1 mRNA expression was significantly increased in ACC tissues from stage IV patients compared with stage I, II, and III patients (p<0.0005, p<0.05, and p<0.05, respectively). Furthermore, increased YME1L1 mRNA expression was inversely correlated with survival and disease-free interval in ACC patients (p<0.01).

Conclusion: YME1L1 is highly expressed in ACC tissues and inversely correlated with patient prognosis, suggesting its potential as a prognostic biomarker for ACC patients and providing new insights into its role in tumor biology. Further studies are needed to elucidate its therapeutic significance and mechanistic contribution to the malignant progression of ACC.

Background/aim: Liquid nitrogen-treated autografts are increasingly used in limb-salvage surgery because they preserve bone strength, maintain biological activity, and may enhance antitumor immunity. However, the true clinical performance of this technique remains controversial, particularly regarding graft survival and postoperative limb function.

Patients and methods: We retrospectively analyzed 10 patients (11 limbs) who underwent reconstruction with liquid nitrogen-treated autografts. Graft survival was assessed using Kaplan-Meier analysis, and postoperative function was evaluated using the International Society of Limb Salvage (ISOLS) score. Potential risk factors were analyzed using univariate statistics.

Results: At four years postoperatively, 72.7% of grafts remained available. Kaplan-Meier analysis demonstrated an impressively long mean graft survival of 156.5 months (95% confidence interval=96.1-217), underscoring the durability of this technique. No clinical variable - including age, diagnosis, fixation method, blood loss, or operative time - showed any significant association with graft failure. In contrast, graft length emerged as the sole parameter strongly linked to functional impairment, demonstrating a significant negative correlation with ISOLS scores.

Conclusion: The primary weakness of this technique lies not in graft survival but in functional decline associated with longer graft segments. These results emphasize the need for careful patient selection and strategic planning yet firmly support liquid nitrogen-treated autografts as a promising reconstructive option - especially in anatomical regions unsuitable for endoprosthesis replacement and in younger patients requiring joint-preserving strategies.

Background/aim: Iodine-Hoechst (IH) is a derivative of Hoechst dye that binds minor grooves of DNA. This chemical has been used for cell labeling studies such as nuclear staining; however, its use in radiation therapy has not been explored fully. We investigated enhancement of X-ray sensitivity of cancer cells by IH.

Materials and methods: Cell survival was examined over a range of X-ray doses, survival curves were generated, and the enhancement ratio (ER) was calculated. Double-strand DNA breaks were examined by a γH2AX assay. We then investigated whether the radiosensitivity-enhancing effect of IH occurs under low oxygen conditions. Additionally, reactive oxygen species (ROS) production was measured using dichlorodihydrofluorescein diacetate. As a first step to investigate the effect of IH on X-ray inhibition of tumor growth, we employed the chorioallantoic membrane (CAM) assay, a simple, versatile cancer model.

Results: IH enhanced X-ray sensitivity of cancer cells, with an ER of 1.29 based on 10% survival values. X-ray-induced DNA double-strand breaks were increased by IH. Upon exposing cells to low oxygen conditions, X-ray sensitivity decreased, consistent with the idea that X-ray sensitivity decreases under low oxygen. Even under this condition, IH enhancement persisted, revealing that the radiosensitivity-enhancing effect was not significantly affected by oxygen. This enhancement does not involve ROS, as X-ray-induced ROS production was unchanged by IH. In the CAM assay, transplantation of cancer cells led to tumor formation within the egg. Intravenous injection of IH resulted in the delivery of IH to the tumor. X-ray irradiation of the tumor inhibited tumor growth, and this was enhanced by IH.

Conclusion: Our results reveal that IH enhances radiation sensitivity of cancer cells, and this effect is observed even under low oxygen conditions.

Background/aim: Vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. However, the clinicopathological and prognostic significance of VEGF expression gallbladder cancer (GBC) remains incompletely defined. This study evaluated the significance of VEGF expression in resected GBC specimens.

Patients and methods: We retrospectively reviewed 53 patients who underwent curative resection for GBC between 2001 and 2019. VEGF expression was evaluated using immunohistochemistry (IHC) in carcinoma tissues and paired non-cancerous mucosa.

Results: VEGF positivity was more frequent in carcinomas than in non-cancerous mucosa [24/53 (45%) vs. 6/46 (13%); p<0.001]. VEGF-positive carcinomas had higher recurrence rate than VEGF-negative cases [11/24 (46%) vs. 4/29 (14%); p=0.0145] and more frequent perineural invasion [9/24 (38%) vs. 2/29 (7%); p=0.0145). Five-year overall survival was lower in the VEGF-positive group than in the VEGF-negative group (64.7% vs. 88.2%; p=0.0218).

Conclusion: VEGF expression in GBC was associated with adverse pathological features and poorer survival after curative resection. VEGF immunostaining in resected specimens may provide prognostic value and help identify patients at higher postoperative risk stratification.

Background/aim: The improved overall survival rates associated with advanced-stage ovarian cancer primarily reflect the surgeon's capacity to remove all residual disease following either primary debulking surgery (PDS) and chemotherapy or via neoadjuvant chemotherapy and interval debulking surgery (IDS). The aim of this study was to compare the survival rates in ovarian cancer following either PDS or IDS.

Materials and methods: We conducted an extensive PubMed search incorporating review articles, retrospective studies, and randomized control trials on the topic of ovarian cancer, with specific terms that included ovarian cancer, PDS, IDS, overall survival, and intraoperative outcomes.

Results: While several investigations have indicated that PDS and IDS confer equivalent survival outcomes, additional results suggested that PDS is associated with improved survival compared to IDS, especially in patients amenable to a gross total resection.

Conclusion: Despite the reportedly similar overall survival outcomes in ovarian cancer, IDS is indicated with elderly or frail patients and in the presence of significant co-morbidities; alternatively, PDS may be preferable in ovarian cancer cases wherein an upfront gross total resection can be readily achieved.

Background/aim: Neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is the standard treatment for locally advanced esophageal squamous cell cancer (ESCC) in Japan; however, reliable markers for early treatment efficacy prediction remain unclear.

Patients and methods: Seventy-one consecutive patients underwent NAC-DCF followed by esophagectomy in September 2012-October 2024. Tumor reduction rate (TRR), defined as the percentage decrease in the tumor area (short diameter×long diameter) after two courses of NAC-DCF, was evaluated using computed tomography (CT). We analyzed the relationship between TRR, clinicopathological parameters, and survival.

Results: The median TRR was 29.91% (-34.2 to 74.2%). The optimal cut-off value of TRR for predicting pathological response was 20% [area under the receiver operating characteristic curve (ROC)=0.717]. Patients with TRR ≥20% showed a significantly higher proportion of ypT0-2 (68% vs. 33%), ypN0-1 (82% vs. 57%), and R0 resection rate (90% vs. 67%) than those with TRR <20%. In multivariable analyses, TRR ≥20% (HR=8.01, 95%CI=2.21-28.89) was an independent predictive factor for pathological response, and clinical response (HR=4.95, 95% CI=1.08-22.55) and TRR ≥20% (HR=3.03, 95% CI=1.01-13.38) were independent prognostic factors for R0 resection. TRR ≥20% showed a significantly higher 3-year RFS rate than TRR <20% (65.8% vs. 44.4%, respectively; p=0.02).

Conclusion: TRR after two courses of NAC-DCF may be a good predictor of pathological response, R0 resection, and prognosis in patients with ESCC undergoing NAC-DCF plus surgery.

Background/aim: Peritoneal surface malignancies, including colorectal peritoneal metastases (CRPM) and peritoneal mesothelioma (PM) carry poor prognoses. The advent of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly altered the treatment landscape, offering selected patients the potential for prolonged survival and improved quality of life. This study evaluated perioperative and oncological outcomes following CRS and HIPEC for CRPM and PM at a single tertiary center.

Patients and methods: A retrospective review was conducted using a prospectively maintained database (CALHN reference Q20160412) from 2012-2024 at the Queen Elizabeth Hospital, South Australia.

Results: A total of 67 CRS procedures on 62 patients with CRPM and 21 procedures on 19 patients with PM were performed. Complete cytoreduction (CC0/CC1) was achieved in 74.6% and 60.0% patients, respectively. Median overall survival for patients with CRPM was 25 months, with a 53% 2-year and a 23% 5-year survival rate. For patients with PM, the 2-year and 5-year overall survival was 58% and 33% respectively. In patients with CRPM, incomplete cytoreduction and high peritoneal carcinomatosis index were independently associated with poorer outcomes.

Conclusion: In our 12-year experience, outcomes were primarily determined by cytoreduction completeness and disease burden, with long-term survival achievable through careful patient selection and specialized surgical care.

Background/aim: Leucine-rich α2-glycoprotein-1 (LRG1), a secreted glycoprotein involved in inflammation, angiogenesis, and tumor progression, has been proposed as a biomarker in several malignancies. However, its clinical relevance in gastric cancer (GC), particularly in curatively resected locally advanced disease, remains unclear. This study aimed to evaluate the prognostic significance of tumoral LRG1 protein expression in patients with pathological stage (pStage) II/III GC after R0 resection.

Patients and methods: A total of 508 patients with pStage II/III GC who underwent R0 gastrectomy with D2 or more extensive lymphadenectomy between 2011 and 2020 were retrospectively analyzed. Tissue microarrays were constructed from three representative tumor regions (tumor center, peripheral area, and invasive front). LRG1 expression in tumor cells was examined by immunohistochemistry and quantified using AI-assisted digital image analysis (HALO^®). Patients were classified into high or low LRG1 expression groups according to the median proportion (42%) of moderately/strongly positive tumor cells. Associations between LRG1 expression, clinicopathological factors, and overall survival (OS) were assessed.

Results: High tumoral LRG1 expression was significantly associated with male sex and poorer prognosis. The 5-year OS rate was significantly lower in the high LRG1 group than in the low LRG1 group (57.5% vs. 68.7%, p=0.0085). In multivariate Cox regression analysis, high LRG1 expression remained an independent adverse prognostic factor for OS (HR=1.472; 95% CI=1.013-2.141; p=0.042).

Conclusion: High LRG1 protein expression in primary tumor cells is an independent predictor of poor survival in patients with pStage II/III GC after curative resection. Quantitative assessment of tumoral LRG1 may serve as a useful prognostic biomarker for risk stratification in locally advanced GC.

Background/aim: For women with early stage, node negative breast cancer undergoing breast conservation, guidelines have shifted towards recommending partial breast radiation (PBI) rather than whole breast radiation. However, application of PBI has been somewhat slow in some settings, particularly in the United States. In this retrospective study, we sought to evaluate tolerance, toxicity and outcomes in women who elected PBI in a large community-based practice.

Patients and methods: A total of 180 women aged 40 years or older were treated with PBI at our institution between 2018-2022 after undergoing lumpectomy with negative margins. Radiation dose regimens included 40 Gy in 15 fractions (Fxs), 35 Gy in 10 Fxs, 30 Gy in 5 Fxs, and 26 Gy in 5 Fxs, all delivered once daily using external beam radiation therapy. Outcome data collected included short and long term toxicities, local recurrence, regional recurrence, distant recurrence, death, endocrine therapy compliance, and follow-up time.

Results: Median follow up was 50.5 months and median age was 65.5 years. Most patients (80%) had invasive cancer and 20% had ductal carcinoma in situ. Of those who were ER+, 89.3% initiated endocrine therapy and 22% stopped endocrine therapy prematurely. Short term grade 2 side effects were noted in 8 women (4.4%). There were no grade 3+ side effects. There were two (1.1%) grade 2 long term side effects consisting of persistent breast pain, and both were in women who received 30Gy/5Fx. There was one local recurrence, diagnosed at 70 months after completion of radiation and one regional and distant metastatic recurrence at 34 months.

Conclusion: Partial breast radiation in this large community-based setting was very well tolerated, with minimal long-term side effects and only one local recurrence.