Anticancer research最新文献

Background/aim: Immuno-oncology (IO) improves the prognosis of advanced renal cell carcinoma (RCC). Since research has so far been limited to clinical trials, we herein focused on the effects of IO-tyrosine kinase inhibitor (TKI) combination therapy in real-world clinical settings.

Patients and methods: We conducted a retrospective study on 125 patients with advanced RCC who received IO-TKI combination therapy or TKI monotherapy. Oncological outcomes were assessed by progression-free survival (PFS) and overall survival (OS), and prognostic factors for PFS and OS were investigated. We then evaluated PFS and OS based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

Results: The IO-TKI group showed significantly longer median PFS (18.6 months vs. 10.1 months, p=0.008) and OS (not reached vs. 34.2 months, p=0.041) than the TKI group. A multivariate analysis identified the Karnofsky performance risk score, first-line therapy (IO-TKI combination therapy or TKI monotherapy), and high C-reactive protein levels as poor prognostic factors for both PFS and OS. PFS did not significantly differ in IMDC favorable-risk patients between the groups but was significantly longer in IMDC intermediate- and poor-risk patients in the IO-TKI group than in the TKI group. OS did not significantly differ in IMDC favorable- and intermediate-risk patients between the groups but was significantly longer in IMDC poor-risk patients in the IO-TKI group.

Conclusion: We demonstrated the advantage of IO-TKI combination therapy compared to TKI monotherapy in real-world clinical settings. However, in IMDC favorable patients PFS and OS did not significantly differ to TKI monotherapy. This may indicate the need for caution when selecting treatment options for IMDC favorable-risk patients.

Background/aim: New treatment agents for advanced non-small cell lung carcinoma (NSCLC) have improved overall survival (OS) in the last 20 years. Nevertheless, treatment strategies for patients with NSCLC and pulmonary fibrosis have not yet been established. This study aimed to evaluate OS improvement in patients with stage IV NSCLC based on the underlying pulmonary diseases.

Patients and methods: This study retrospectively reviewed 581 patients with stage IV NSCLC who received any antineoplastic agents. Patients were categorized into three groups based on their underlying pulmonary conditions: normal lungs, emphysema, and fibrosis. Additionally, patients were divided into four periods: A (2002-2006), B (2007-2011), C (2012-2016), and D (2017-2021). OS of patients with each underlying pulmonary disease was compared across the different periods and treatment agents [cytotoxic agents (CYs) only, molecular-targeted tyrosine kinase inhibitors (TKIs), and immune checkpoint inhibitors (ICIs)].

Results: Emphysema and fibrosis were identified in 205 (35.3%) and 54 (9.3%) patients, respectively. Over the last two decades, the OS (months) of all patients improved (p<0.001), including patients with normal lungs (p=0.004) and patients with emphysema (p<0.001), but with no significant improvement in fibrosis (p=0.605). TKI and ICI improved OS in patients with normal lungs (p<0.001) and emphysema (p<0.001), but had no significant impact on OS in patients with fibrosis (p=0.502).

Conclusion: Patients with advanced NSCLC have improved prognoses in the last 20 years except for patients with pulmonary fibrosis. To improve the prognosis of patients with lung cancer and pulmonary fibrosis, new strategies and treatments should be developed.

Background/aim: Atezolizumab plus bevacizumab (AteBev) is widely used as a first-line treatment for advanced hepatocellular carcinoma (HCC). However, evidence regarding the optimal drug sequence following AteBev treatment is limited. This study aimed to compare the treatment outcomes between tyrosine kinase inhibitors (TKIs) and durvalumab plus tremelimumab (DurTre) following AteBev treatment.

Patients and methods: Overall, 134 consecutive patients who received AteBev for advanced HCC were enrolled in this study. Treatment outcomes were retrospectively compared between TKIs (AteBev→TKI group) and DurTre (AteBev→DurTre group).

Results: The AteBev→TKI and Ate→DurTre groups included 46 and 7 patients, respectively. The AteBev→TKI group had significantly longer median progression-free survival after second-line treatment (3.6 vs. 0.94 months, p<0.001). The disease control rate was significantly higher in the AteBev→TKI group (p=0.020). The serum alpha-fetoprotein levels significantly decreased at one month in the AteBev→TKI group (0.909 vs. 1.435, p=0.035), whereas the albumin-bilirubin score significantly decreased at one month in the AteBev→TKI group (0.875 vs. 0.952, p=0.017). Each group reported no new unmanageable adverse events.

Conclusion: TKIs may be a more optimal drug sequence than DurTre after AteBev treatment from an oncological perspective. TKIs following AteBev treatment require careful monitoring for deteriorating liver function.

Background/aim: For patients with unresectable locally advanced pancreatic cancer (LAPC), carbon-ion radiotherapy (C-ion RT) can safely deliver higher doses than conventional photon therapy, increasing the potential for long-term survival. However, achieving meaningful improvements in survival rates requires reliable prognostic biomarkers to identify patients likely to benefit from treatment.

Patients and methods: In this study, we measured plasma levels of soluble interleukin-6 receptor (sIL-6R) before C-ion RT and examined their association with the risk of distant metastasis (DM), local recurrence (LR), and overall survival (OS).

Results: Results showed that patients with higher plasma sIL-6R levels had a lower risk of DM [hazard ratio (HR)=0.53; p=0.033] and improved OS (HR=0.55; p=0.037). No significant association was observed between LR and plasma sIL-6R levels (HR=1.47; p=0.273).

Conclusion: These findings suggest that pretreatment plasma sIL-6R levels may serve as a prognostic marker for C-ion RT in LAPC.

Background/aim: Epidermal growth factor receptor (EGFR) exon 19 insertions are very rare mutations and their response to tyrosine kinase inhibitors (TKIs) is uncertain. We report our experience concerning two patients, along with a literature review.

Patients and methods: A total of 1,046 non-small-cell lung cancer tumor tissue samples were screened for EGFR mutations, using direct sequencing or next-generation sequencing. Two patients presented the same insertion of 18 nucleotides in EGFR exon 19 and were treated with afatinib.

Results: Both patients responded to afatinib, showing a stable disease (SD) and a progression-free survival (PFS) of 6 and 10 months along with an overall survival (OS) of 17 and 19 months, respectively. A review of the literature data concerning clinical responsiveness to different generations of TKIs in patients with EGFR exon 19 insertions, including data of our two patients (n=28), showed a response rate of 64% and disease control rate of 92%. The calculated median PFS for the 28 cases, independently of the TKIs administered, was 9 months; median OS (n=15) was 13 months. Median PFS for patients receiving gefitinib and erlotinib was 9 months and 12.5 months, respectively, consistent with the median PFS observed in patients with "classical" EGFR mutations, treated with these agents.

Conclusion: Patients with EGFR insertions in exon 19 have demonstrated sensitivity to treatment with EGFR TKIs, suggesting that patients carrying these mutations should be treated with these inhibitors.

Background/aim: Vascular pain associated with NK1 receptor antagonists, particularly fosaprepitant, remains a significant challenge in cancer chemotherapy. The present study investigated the incidence of vascular pain with the administration of fosaprepitant and fosnetupitant and assessed the psychological burden on nurses performing venipuncture.

Patients and methods: We conducted a prospective observational study involving 115 cancer patients receiving NK1 receptor antagonists via peripheral venous catheters. Vascular pain was evaluated using a numerical rating scale. Nurses' psychological burden was assessed through questionnaires and a qualitative analysis.

Results: Vascular pain occurred in 19% of 304 venipunctures, and its incidence was significantly lower with fosnetupitant (3.1%) than with fosaprepitant (22.9%) (p<0.01). Switching from fosaprepitant to fosnetupitant reduced pain in all cases. Nurses experienced psychological burden in 97% of venipunctures, with severe distress (NRS ≥3) in 19% of cases. The qualitative analysis revealed that nurses' distress was affected by the vascular status, patient behavior, and concerns about drug administration.

Conclusion: The incidence of vascular pain was lower with fosnetupitant than with fosaprepitant. Nurses experienced significant psychological burden during venipuncture, particularly when patients reported pain. These results suggest that fosnetupitant is a preferable option for reducing both patient discomfort and nurses' psychological burden in chemotherapy administration.

Background/aim: Two retrospective studies of prospective cohorts showed doubled odds of birth asphyxia among women with low plasma vitamin D levels, and another study reported a four-fold increased risk of stillbirth. It was not known whether this was related to low sun exposure or to insufficient vitamin D per se. We aimed to assess if it was due to vitamin D status.

Patients and methods: We analyzed the incidence of stillbirth in relation to national vitamin D status for all pregnancies in Finland and Sweden between 1994 and 2021 (n >4.3 million). Due to 50% of the population having low plasma vitamin D, Finland implemented an extensive vitamin D food fortification program in 2003 and doubled it in 2009 because of inadequate results. After 2009, 10% of Finnish women had low vitamin D levels. Stillbirth incidence was related to changes using cross-tabulation with 95% confidence intervals.

Results: The stillborn incidence in Finland decreased from 4.1/1,000 (prior to 2003), to 3.4/1,000 (2004 to 2009), and to 2.8/1,000 after 2009. In the meantime, the Swedish stillbirth rate remained constant at 3.9/1,000 until 2018, when the Finnish food fortification plan was implemented in Sweden. Thereafter, the Swedish stillbirth incidence dropped to 3.2/1,000. The rate of intrahepatic cholestasis of pregnancy, another hypoxic pregnancy complication related to low plasma vitamin D levels, did not drop.

Conclusion: In our large study of national vitamin D food fortification, improved vitamin D status was associated with a lower stillbirth rate in a dose-dependent manner.

Background/aim: Liver metastasis (LM), pre-dominant in pancreatic cancer, is associated with a dismal 5-year survival rate. Reports on the presence of fatty liver and liver fibrosis in LM are conflicting. Although liver biopsy is the standard diagnostic method for fibrosis, alternative, less invasive scoring models have been explored. This study examined the relationship between preoperative liver conditions and metachronous LM in patients undergoing pancreaticoduodenectomy (PD) for pancreatic head cancer.

Patients and methods: We conducted a retrospective study on patients with pancreatic head cancer who underwent surgery at a single University Hospital between 2008 and 2023. The primary focus was the effect of preoperative liver conditions on LM recurrence. We compared clinical variables between groups with LM recurrence and those with extrahepatic recurrence. Liver conditions were evaluated using the Fibrosis-4 (FIB-4) index, NAFLD-fibrosis score (NFS), aspartate aminotransferase (AST) to platelet (PLT) ratio index (APRI), and AST to alanine aminotransferase (ALT) ratio.

Results: Fifty patients who underwent macroscopic curative surgery for pancreatic head cancer were analyzed. We observed LM and extrahepatic recurrences in 15 (30%) and 19 patients (38%), respectively. The extrahepatic recurrence group included two patients with viral hepatitis and one with alcoholic chronic pancreatitis. Preoperative factors and plain CT scans revealed significantly lower platelet levels and liver-to-spleen ratios, respectively, in the extrahepatic recurrence group. The FIB-4 index and NFS were significantly higher in the extrahepatic recurrence group than in the LM recurrence group.

Conclusion: High preoperative FIB-4 Index and NFS scores could be potential predictors for reduced metachronous LM following PD for pancreatic head cancer.

Background/aim: In a tongue-submandibular lymph node (SLN) metastasis model, the cystine/glutamate transporter solute carrier family 7, member 11 (Slc7a11), also known as xCT, was found to increase in lymphatic endothelial cells (LECs) within SLNs prior to melanoma cell metastasis. However, the precise mechanism by which xCT influences LECs remains unclear. This study aimed to explore the role of xCT in primary cultured LECs.

Materials and methods: To determine whether xCT is involved in cystine uptake and glutathione (GSH) synthesis in primary cultured LECs, cystine uptake and GSH assays were conducted. The antioxidant role of xCT was evaluated by measuring intracellular reactive oxygen species (ROS). Additionally, xCT expression was analyzed in human melanoma metastatic lymph nodes using immunohistochemical staining.

Results: Slc7a11-knockdown LECs exhibited significantly reduced cystine uptake and intracellular GSH levels. ROS levels in Slc7a11-knockdown LECs were found to be increased compared to those in control LECs under H₂O₂-induced oxidative stress conditions. xCT stability is regulated by CD44v; therefore, we evaluated whether LYVE-1, a hyaluronic acid receptor in LECs, regulates xCT expression. LYVE-1 upregulates Slc7a11 mRNA expression, increasing GSH production in LECs. Furthermore, xCT expression was observed in LECs within human melanoma metastatic lymph nodes.

Conclusion: xCT functions as a cystine transporter, contributing to increased GSH levels in lymphatic fluid in melanoma metastasis.

Background/aim: This study aimed to predict the optimal timing for adaptive radiation therapy (ART) using two-dimensional X-ray image-based water equivalent thickness (2DWET).

Patients and methods: Forty patients with oropharyngeal and hypopharyngeal cancer underwent Computed Tomography (CT) rescanning during treatment. An adaptive score (AS) was proposed to guide ART decisions based on changes in four dose indices: target coverage, spinal cord dose, parotid gland dose, and over-dose volume. Delivered dose distributions were reviewed by two head and neck radiation oncologists, with ART requirement evaluated using a four-point scale. Logistic regression determined the AS cutoff, while receiver operating characteristic analysis assessed 2DWET as a predictor of ART timing.

Results: The AS strongly correlated with the oncologists' ART decisions (Pearson coefficients of 0.74 and 0.64). An AS cutoff of 7.5 optimally indicated ART requirement, matching oncologist decisions with sensitivities of 79.2% and 89.5%, and specificities of 87.5% and 81.0%, respectively. The 2DWET method identified the AS threshold of 7.5 with sensitivity and specificity of 63.2% and 81.0%.

Conclusion: An AS of 7.5 was highly indicative of ART timing, aligning well with oncologists' decisions, and 2DWET demonstrated potential as a low-exposure, efficient tool for predicting ART timing in patients with oropharyngeal and hypopharyngeal cancers.