International Journal of Clinical Oncology最新文献

Background: Sequential therapy with different novel androgen receptor signaling inhibitors (ARSIs) is a possible treatment option for patients who have increased prostate-specific antigen (PSA) levels. The aim of the present study was to investigate cross-resistance among ARSIs and its predictors in non-metastatic castration-resistant prostate cancer (nmCRPC).

Methods: In this multicenter retrospective study, we evaluated 75 patients with nmCRPC who had progressed after treatment with one ARSI and were subsequently treated with a second ARSI. The primary endpoint was cross-resistance among ARSIs, which was identified by comparing PSA responses to treatment with first and second ARSIs. The secondary endpoints were changes in PSA doubling time (PSADT) from diagnosis of nmCRPC to initiation of treatment with a second ARSI and predictors of PSA non-responsiveness to treatment with that second ARSI.

Results: The rates of any PSA response, PSA decline ≥ 50%, and PSA decline ≥ 90% to treatment with a second ARSI were significantly lower than those to the first ARSI administered (45% vs. 88%, P < 0.001; 9.3% vs. 71%, P < 0.001; 2.7% vs. 33%, P < 0.001; respectively). The PSADT shortened to some degree in 31 patients (41%). According to multivariable analysis, only PSADT before initiation of treatment with a second ARSI was significantly associated with no PSA response to treatment with that second ARSI.

Conclusions: We identified significant cross-resistance among ARSIs in patients with nmCRPC. The PSADT before initiation of treatment with a second ARSI may be useful for predicting the efficacy of treatment with a second ARSI.

Background: The incidence of early-onset colorectal cancer (EoCRC), defined as a CRC diagnosed in individuals younger than 50 years, has been increasing globally. The clinicopathological differences between EoCRC and late-onset CRC (LoCRC: diagnosed in individuals older than 50 years) are suggestive of distinct genomic landscapes. The aim of this study was to assess the differences in genomic alterations in Japanese patients with EoCRC and LoCRC from multiple institutions across Hokkaido using comprehensive genomic profiling data.

Methods: The patient's background, CRC location, pathological findings, clinical stage at presentation, prognosis, and genomic alterations of the EoCRC and LoCRC groups were compared.

Results: A total of 317 CRC patients were analyzed, including 61 with EoCRC and 256 with LoCRC. Right-sided CRC and differentiated histology were significantly less common in the EoCRC group. There was no significant difference in the median survival duration between the two groups. Genomic profiling revealed significantly higher frequency of SMAD4, FLT3, and CDK8 alterations in EoCRC patients compared to LoCRC patients (p = 0.016, p = 0.023, and p = 0.035, respectively). Cell cycle pathway alterations were also significantly enriched in the EoCRC group (p = 0.003). Additionally, SMAD4 mutations were associated with poor prognosis in both groups.

Conclusions: SMAD4, FLT3, and CDK8 alterations were significantly more prevalent in EoCRC patients, suggesting that these genes likely contribute to the distinct molecular pathogenesis of EoCRC, and may also serve as potential therapeutic targets. Further studies are warranted to elucidate their biological significance and explore their potential in the development of targeted therapies for Japanese patients with EoCRC.

Background: The morphological classification of perihilar cholangiocarcinoma (pCCA) may influence survival outcomes following curative resection. This study aimed to evaluate the impact of different morphological subtypes on long-term survival.

Methods: We conducted a retrospective analysis of 167 patients with pCCA who underwent curative resection between 2013 and 2018. Patients were classified into three morphological subtypes: intraductal growth (IG-type), periductal infiltrating (PI-type), and mass-forming/mixed (MF-type).

Results: Among the 167 resected patients, the PI-type was most prevalent (53.3%), followed by the IG-type (25.7%) and MF-type (21.0%). Within this surgical cohort, the IG-type was associated with the most favorable prognosis, exhibiting a significantly longer median OS (21.0 months) compared to the PI-type (15.9 months) and MF-type (14.5 months). Multivariable analysis identified positive RM and LNM as the independent predictors of both poor OS and RFS. A critical interaction was observed: in LNM-negative patients, achieving an R0 resection conferred a significant survival benefit across all morphological subtypes. However, in LNM-positive patients, survival was uniformly poor, and the prognostic impact of RM status was completely attenuated.

Conclusion: Among patients with resectable pCCA, morphological subtype is associated with distinct prognostic profiles. However, the ultimate determinants of survival outcome are the RM status and the status of LNM. Achieving an R0 resection is paramount in LNM-negative disease, whereas LNM positivity dictates a poor prognosis regardless of margin status. This underscores the dominant roles of margin status and nodal involvement in risk stratification and in guiding decisions for adjuvant therapy.

Despite advancements in technology and research in clinical oncology, colon cancer remains a leading cause of cancer-related deaths worldwide. Hypoxic conditions, characterized by diminished oxygen levels in the tumor microenvironment, have been implicated in the tumorigenesis of various types of cancer. HIF-1α, as a principal hypoxic transcription factor, promotes tumor progression by interacting with multiple molecular pathways and oncogenic functions. Various studies have demonstrated that HIF-1α can promote the growth and development of colon tumor cells by stimulating downstream target genes through multiple mechanisms, such as immune evasion, cancer stem cell enrichment, metastasis, invasion, angiogenesis, and glycolysis. In this review, we comprehensively discuss the mechanisms and functions of HIF-1α that contribute to the growth and progression of colon cancer in the hypoxic tumor microenvironment.

Background: The 1846C > T polymorphism of the C-reactive protein (CRP) gene is associated with an increased risk of lymph node metastasis in various cancers. This study aimed to examine its association with lymph node metastasis in gastric cancer.

Methods: A retrospective analysis of the 1846C > T CRP polymorphism was conducted in patients with submucosal (SM) gastric cancer from April 2011 to March 2022. Genotyping was performed using polymerase chain reaction fragment length polymorphisms. Patients were categorized into differentiated and undifferentiated groups and then subdivided into C/C + C/T and T/T genotypes. We assessed correlations between polymorphisms, lymph node metastasis, and lymphatic and venous invasion. Two sub-analyses were conducted in the differentiated gastric cancer group.

Results: Among 111 patients with SM gastric cancer, 81 had differentiated tumors, whereas 30 had undifferentiated tumors. In the differentiated group, 4.5% of C/C and C/T genotypes and 18.9% of T/T genotypes exhibited lymph node metastasis, with a 95% negative predictive value. Excluding pT1b1 and tumors ≤ 3 cm, lymph node metastasis occurred in 5.3% of C/C and C/T genotypes and 20.6% of T/T genotypes, with a negative predictive value of 94.7%. For cT1bN0 cases, lymph node metastasis was 0% in C/C and C/T genotypes and 15.8% in T/T genotypes, with a negative predictive value of 100%.

Conclusions: In this exploratory study, the 1846C > T CRP polymorphism suggests that patients with differentiated SM gastric cancer carrying the C/C or C/T genotype have reduced risk of lymph node metastasis, potentially minimizing the need for additional surgery after endoscopic submucosal dissection.

Background: Immune checkpoint inhibitors (ICIs) have improved treatment outcomes for gastric cancer. However, immune-related adverse events (irAEs) pose a major challenge. This study aimed to identify predictive factors for irAE occurrence in patients with advanced or recurrent gastric cancer treated with nivolumab.

Methods: We retrospectively analyzed information of 115 patients with advanced or recurrent gastric cancer treated with nivolumab monotherapy or in combination with chemotherapy. Patient characteristics and laboratory data, including complete blood counts, and clinical outcomes were analyzed. Optimal cutoffs for potential predictive factors were determined using ROC curve analysis.

Results: irAEs developed in 21 patients, with a median onset time of 124 days after treatment initiation. Patients with an eosinophil proportion ≥ 4% showed higher irAE rates compared to those with < 4%. Multivariate analysis identified eosinophil proportion ≥ 4% (odds ratio 5.0) and neutrophil-to-lymphocyte ratio < 1.9 (odds ratio 4.6) as independent predictors of irAE occurrence. Patients with an elevated eosinophil proportion had higher levels throughout the treatment than those without irAEs at baseline, two months, and three months after treatment initiation. Patients with eosinophil proportions ≥ 4% demonstrated better overall survival and a tendency toward improved progression-free survival.

Conclusion: Elevated eosinophil proportion before ICI treatment was a predictor of irAE occurrence and was associated with improved survival in patients with advanced or recurrent gastric cancer. This readily available clinical parameter may help identify patients more likely to benefit from ICI therapy, while enabling closer monitoring of potential irAEs.

Triple-negative breast cancer (TNBC) is best characterized by high aggressiveness and significant biological heterogeneity. Although the current TNBC clinical trials include genomic biomarkers to stratify treatment arms, they are still limited by metabolic heterogeneity within TNBC subtypes. The metabolic reprogramming, a cancer hallmark, in TNBC involves adaptive regulation of glycolysis, lipid metabolism, and oxidative phosphorylation (OXPHOS), with distinct metabolic phenotypes significantly influencing tumor sensitivity to treatment. Mitochondrial heterogeneity exacerbates the metabolic diversity of TNBC, with its dynamic functional regulation closely linked to cellular energy metabolism and signaling pathway adaptation. Interplay between OXPHOS, metabolites, and immune activity creates a self-reinforcing mechanism where metabolic adaptations in TNBC cells not only support their energy demands but also actively construct an immune-privileged niche that shields tumors from immune surveillance and limits the efficacy of treatments. These mechanisms and mitochondrial diversity could be heterogeneous and specific to TNBC subtypes. Thus, metabolic phenotyping of TNBC subtypes could reveal previously unidentified patient subgroups, potentially explaining divergent survival outcomes and offering metabolism-targeted therapeutic strategies that might improve outcomes for patients who currently lack effective treatment alternatives.

The number of deaths from colorectal cancer in Japan continues to rise, with over 50,000 deaths recorded in 2018. In the 2024 edition, revisions to all aspects of treatment were undertaken, with corrections and additions made based on knowledge gained since the 2022 version (drug therapy) and the 2019 version (other treatments). The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2024 for the treatment of colorectal cancer have been prepared to present standard treatment strategies, reduce disparities among institutions, avoid both unnecessary and insufficient treatment, and enhance mutual understanding between healthcare professionals and patients by making these guidelines accessible to the public. These guidelines were developed through consensus by the JSCCR Guideline Committee, following a careful review of evidence retrieved from literature searches and considering the medical insurance system and actual clinical practice in Japan. Therefore, these guidelines serve as a tool for managing colorectal cancer in real-world clinical settings. More specifically, they can be used to support obtaining informed consent from patients and selecting the most appropriate treatment method for each patient. Controversial topics were selected as clinical questions, and recommendations were provided. Each recommendation is accompanied by an evidence classification and a recommendation category, both based on consensus reached by the Guideline Committee members. This article presents the English version of the JSCCR guidelines 2024.

Background: Pathological T1a-muscularis mucosa with lymphovascular invasion and T1b-submucosa are high-risk factors for lymph node metastasis in esophageal squamous cell carcinoma (ESCC). Esophagectomy and chemoradiotherapy are recommended following endoscopic submucosal dissection (ESD) but can lead to complications. Here, we evaluated the efficacy and safety of chemotherapy following ESD.

Methods: This prospective and retrospective study included patients with pathological T1a-muscularis mucosa with lymphovascular invasion or T1b-submucosa who underwent esophageal ESD between June 2006 and August 2023, followed by chemotherapy or chemoradiotherapy. The overall survival, cause-specific survival, recurrence-free survival, hospitalization period, and the occurrence of grade ≥ 3 adverse events were compared between the chemotherapy and chemoradiotherapy groups.

Results: The patient and tumor characteristics and pathological findings did not significantly differ between the chemotherapy (n = 16) and chemoradiotherapy (n = 15) groups. The 5-year overall and recurrence-free survival rates were significantly higher in the chemotherapy group than in the chemoradiotherapy group (100.0% vs. 77.8%, P < 0.001 and 92.3% vs. 84.9%, P = 0.007, respectively; log-rank test). The 5-year cause-specific survival rate did not significantly differ between groups (100.0% vs. 83.3%, P = 0.14, log-rank test). The hospitalization period was significantly shorter in the chemotherapy group than in the chemoradiotherapy group (34 vs. 48 days, P < 0.001). Grade ≥ 3 adverse events occurred in 4 (25.0%) and 11 (73.3%) patients in the chemotherapy and chemoradiotherapy groups, respectively.

Conclusions: Chemotherapy is a safe and effective additional treatment for ESCC (pathological T1a-muscularis mucosa with lymphovascular invasion or T1b-submucosa) after ESD.