International Journal of Clinical Oncology最新文献

Background: Fat-free mass index (FFMI) is a prognostic influence in cancer patients. However, for the prognosis of Chinese lung cancer (LC) patients, the threshold and impact of FFMI are not known. The aim of the present study was to examine the association between FFMI and the prognosis of Chinese patients with LC.

Methods: Totally 1,881 adult patients with LC were enrolled. During a median follow-up of 41.0 months (range 23.8-64.3), we reported 938 deaths. The optimal stratification method was used to determine the gender-specific optimal threshold for FFMI. Cox regression model and Kaplan-Meier curve were used to evaluate the relationship between FFMI and prognosis. Mediation analysis was used to determine the mediating effect of inflammation.

Results: The optimal cutoff points for low FFMI in males and females were 17.27 kg/m² and 14.84 kg/m², respectively. Low FFMI was an independent prognostic indicator for LC patients. Patients who experienced a low FFMI were 29% more likely to die than patients who did not have a low FFMI (P < 0.001, HR = 1.29, 95%CI: 1.12-1.49). The impact of low FFMI on prognosis in LC patients exhibited significant staging dependence, particularly in advanced non-small cell LC and extensive-stage small cell LC. NLR mediated 9.2% of the associations between FFMI and LC all-cause mortality.

Conclusion: In this prospective study, low FFMI, as determined by cutoff values, was an independent prognostic factor for patients with LC in both males and females. The association between FFMI and LC prognosis was significantly mediated by NLR.

Background: The conventional histomorphology-based risk classification for endometrial cancer (EC) does not consider the molecular heterogeneity that influences prognosis and treatment response. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) system uses next-generation sequencing to assess DNA polymerase epsilon (POLE) mutations, but its high cost limits its accessibility. This study evaluated the prognostic value of a novel algorithm that combined immunohistochemistry (IHC) testing with conventional risk factors.

Methods: This retrospective study included 237 patients with stage I-III EC who underwent surgery. Low-risk patients were classified without IHC, while intermediate- and high-risk patients were categorized as MMR-deficient (MMRd), p53-abnormal (p53abn), or nonspecific molecular profile (NSMP) groups based on IHC. Additionally, L1CAM expression was also evaluated. Survival outcomes were analyzed using Kaplan-Meier curves and Cox regression models.

Results: Data from 233 cases were analyzed; the median follow-up duration was 63 months. Among 87 low-risk patients, only 1 experienced recurrence. The intermediate- and high-risk groups were subdivided into 42 MMRd, 16 p53abn, and 88 NSMP patients. The 5-year disease-free survival (DFS) rates were 98.8% (low-risk), 94.7% (NSMP), 80.6% (MMRd), and 59.8% (p53abn), highlighting the poorer prognosis of p53abn. p53abn independently predicted recurrence (hazard ratio [HR], 10.1) and mortality (HR, 25.6). L1CAM positivity correlated with worse DFS but was not an independent prognostic factor.

Conclusion: Conventional risk classification combined with IHC classification using p53 and MMR is a cost-effective prognostic tool that enables risk stratification and personalized treatment decisions, even when genetic testing is unavailable.

Background: Niraparib is approved for maintenance treatment of tubo-ovarian cancer patients, but data on older patients are limited. This retrospective study evaluated its safety and efficacy in primary advanced tubo-ovarian cancer, focusing on patients ≥ 75 years.

Methods: Women aged ≥ 50 years diagnosed with primary high-grade serous tubo-ovarian cancer, treated with niraparib between 2019-2023, were enrolled. Patients were stratified into three groups: A (50-64 years), B (65-74 years), and C (≥ 75 years). The primary outcome was progression-free survival. The secondary outcomes were toxicity and dose reduction.

Results: 127 patients were identified: 62 (48.8%) group A, 26 (20.5%) group B, and 39 (30.7%) group C. Baseline characteristics were comparable across groups, excluding a higher proportion of interval cytoreductive surgeries (p = 0.001), residual tumor (p = 0.01) and Eastern Cooperative Oncology Group (ECOG) > 1 (p = 0.01) in group C. Most patients started niraparib at 200 mg/day with dose reductions primarily occurred within fourth cycle. Dose reductions were observed in 77.4%, 69.2% and 56.4% of patients in groups A, B, and C, respectively (p = 0.08). In patients ≥ 75 years, 26 (66.7%) discontinued treatment due to disease progression (48.7%) or toxicity (17.9%). There were no significant differences in common or grade ≥ 3 adverse events between groups. Progression-free survival was 12 months (95%CI: 2.0-25.0) for group A, 29 months (95%CI: 11.0-52.0) for group B, and 16 months (95%CI: 1.0-31.0) for group C (p = 0.78).

Conclusions: Our findings suggest that niraparib is safe and well-tolerated in aged ≥ 75 years. Concerns about toxicity should not preclude the enrollment of elderly patients in treatment regiments.

Background: Guideline-consistent prophylaxis is more effective in managing chemotherapy-induced nausea and vomiting than non-guideline approaches. However, the extent to which patients undergoing anticancer treatment receive guideline-recommended antiemetic therapy in real-world clinical practice remains unclear. This study evaluated the real-world patterns of antiemetic therapy among patients undergoing high emetic risk chemotherapy (HEC) and carboplatin-based moderate emetic risk chemotherapy (MEC) according to cancer type and treatment regimen and identified factors associated with antiemetic use.

Methods: We used health service utilization data linked to hospital-based cancer registries from 601 hospitals in Japan. Data from patients aged ≥ 18 years diagnosed with cancer in 2020 and 2021 and treated with intravenous HEC or carboplatin-based MEC were analyzed. The percentage of patients prescribed antiemetics was calculated. A multilevel mixed-effects logistic regression was performed to identify factors associated with antiemetic therapy.

Results: A total of 157,705 patients were analyzed (HEC: 100,163; MEC: 57, 542). Triple-drug antiemetics (an NK₁ receptor antagonist, a 5-HT₃ receptor antagonist, and dexamethasone) were prescribed to 70.6% and 71.9% of patients undergoing HEC and MEC, respectively. In the HEC group, 8.9% received olanzapine in addition to triple-drug antiemetics. Antiemetic therapy varied by cancer type and regimen. In multilevel analysis, odds of receiving triple-drug antiemetics were the highest in small-cell lung cancer (OR = 3.065) for HEC and in endometrial cancer (OR = 1.324) for MEC.

Conclusion: Antiemetic therapy for patients receiving HEC or carboplatin-based MEC varies by cancer type and treatment regimen. Future research should explore reasons for and barriers to non-adherence to guidelines.

Background: Several gemcitabine-based regimens are effective as first-line treatments for advanced biliary tract carcinoma (BTC), while fluorouracil, folinic acid, and oxaliplatin (FOLFOX) is commonly used as second-line therapy in Western countries. This study aimed to investigate the efficacy and safety of FOLFOX in Japanese patients.

Methods: We retrospectively reviewed cases of BTC patients who were refractory to or intolerant of at least one gemcitabine-based regimen and subsequently received FOLFOX. Data on clinical characteristics, adverse events, treatment responses, and patient outcomes were collected. Because the FOLFOX regimen have not been approved in Japan, we have followed the appropriate procedures for the off-label use of FOLFOX in accordance with each institution's regulations and relevant laws and regulations.

Results: A total of 50 patients were included. Grade 3 or higher adverse events occurred in 30 patients (60%), 21 patients (42%) requiring dose reduction, and 24 patients (48%) requiring treatment delays. No treatment-related deaths occurred. The objective response rate (ORR) was 6%, with a disease control rate of 56%. The median progression-free survival (PFS) and overall survival (OS) were 3.4 months and 6.8 months, respectively. Among 14 patients who received FOLFOX as second-line treatment after gemcitabine and cisplatin, the ORR, median PFS, and median OS were 14%, 4.6 months, and 7.5 months, respectively.

Conclusion: This study suggested the efficacy and safety of FOLFOX as a second-line or later treatment option also for Japanese patients with advanced BTC.

Background: The preventive effect of physical activity on the risk of thyroid cancer remains inconsistent and unclear. We investigated the association between physical activity and the risk of thyroid cancer using a meta-analysis of prospective cohort studies.

Methods: A systematic search of PubMed and EMBASE was conducted from inception till December 20, 2024. A pooled relative risk (RR) with its 95% confidence interval (CI) was calculated using an adjusted RR with its 95% CI from each study.

Results: A total of nine prospective cohort studies (N = 2 764 014 adults; incident thyroid cancer cases, 15 166) were included in the final analysis. In the meta-analysis of all the studies, highest physical activity was not significantly associated with the risk of thyroid cancer (RR, 0.91; 95% CI 0.76-1.09; I² = 56.5%), compared with lowest physical activity. Physical activity was statistically significantly associated with a decreased risk of thyroid cancer in the studies conducted in Asia (RR, 0.75; 95% CI 0.64-0.88; I² = 4.2%), but not in either Europe or North America. Also, physical activity was statistically significantly associated with a decreased risk of thyroid cancer in the studies published after 2015 (RR, 0.78; 95% CI 0.65-0.93; I² = 22.1) and the high-quality studies (RR, 0.81; 95% CI 0.70-0.94; I² = 5.2).

Conclusions: Physical activity decreased the risk of thyroid cancer in the studies conducted in Asia, published after 2015, and rated as having high methodological quality. Further high-quality prospective cohort studies are warranted to confirm our findings.

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.