Cancer diagnosis & prognosis最新文献

Background/aim: Tumor intrinsic β-catenin signaling has been reported to influence the tumor immune microenvironment and may be a resistance mechanism to immune checkpoint inhibitors in various cancers.

Patients and methods: We studied the association between tumor β-catenin expression and survival in 50 patients with non-small cell lung cancer (NSCLC) treated with anti-programmed death-1 antibody monotherapy. Tumor β-catenin expression was evaluated by immunohistochemistry.

Results: Patients with positive tumor β-catenin expression (20% of all patients) had worse progression-free survival and overall survival compared with those with negative tumor β-catenin expression. Patients with positive tumor β-catenin expression had reduced CD8⁺ cell and CD11c⁺ cell infiltration into tumor nests than those with negative tumor β-catenin expression. RT-PCR of tumor tissue revealed that patients with positive tumor β-catenin expression showed lower gene expression of CD8A, CD4, IFN-γ, BATF3, and CCL4. Knockdown of CTNNB1 tended to increase CCL4 expression, likely mediated by ATF3, in a lung cancer cell line with positive β-catenin expression.

Conclusion: NSCLC patients with positive tumor β-catenin expression that were treated with anti-programmed death-1 antibody monotherapy had poor prognosis.

Background/aim: The high mortality rate associated with colon cancer in patients with diabetes is well-established; however, the underlying mechanisms have not been fully elucidated. Here, we investigated the efficacy of modified FOLFOX6 (mFOLFOX6) therapy, which is frequently used in colon cancer treatment, in patients with and without comorbid diabetes.

Patients and methods: The participants in this retrospective cohort study received mFOLFOX6 therapy as a first-line treatment for incurable/ unresectable and advanced/recurrent colon cancer. We compared patient background characteristics; number of mFOLFOX6 courses; total dose of each drug; reasons for dose reduction, deferment, or discontinuation; and survival time.

Results: Data of six patients with diabetes and 26 without diabetes were assessed. There was no significant difference in background characteristics between the patient groups, with the exception of blood glucose levels. There was no significant difference in the planned number of mFOLFOX6 courses between the groups; however, the total number of completed courses was significantly lower in patients with diabetes than in those without diabetes. Discontinuation rates due to adverse events were similar between the groups; however, discontinuation due to progressive disease or death was significantly higher in patients with diabetes than in those without diabetes. No significant differences were observed in the total dose of each anticancer drug or survival time between the groups.

Conclusion: mFOLFOX6 may not have sufficient therapeutic effects in patients with diabetes. Therefore, in patients with concurrent diabetes and colon cancer, alternative therapeutic options for cancer treatment should be considered.

Background/aim: Perianal Paget's disease (PPD) is an intraepithelial invasion of the perianal skin that is frequently associated with anorectal carcinoma. Rectal canal carcinoma with Pagetoid spread (PS) is a relatively rare disease, and few reports on its outcomes are available. The relatively rare nature of this disease makes the development of treatment recommendations difficult. This study aimed to clarify the characteristics of the disease and factors related to prognosis. We present a case report and review of 89 cases, including those from the existing literature and our own experience.

Case report: The patient was an 81-year-old man who was referred to our hospital for surgery after endoscopic examination of the lower gastrointestinal tract revealed cancer of the anal canal with PS. Physical examination revealed erythema and erosions around the anus. Lower gastrointestinal endoscopy revealed an erythematous area and a continuous raised lesion in the anal canal. We diagnosed the patient with anal canal carcinoma with PS, and robot-assisted abdominoperineal resection was performed.

Conclusion: Our findings indicate that the five-year survival rate for PPD patients was 63%, comparable to that of anal canal cancer without PS. The histological type and presence of lymph node metastasis may be related to the prognosis. The study suggests that early-stage patients with favorable histological types and no lymph node involvement may benefit from less invasive treatment options, such as endoscopic submucosal dissection.

Background/aim: Metastatic prostate cancer is a recalcitrant disease. Our laboratory has previously treated prostate-cancer patients with methionine restriction effected by a low methionine diet and oral recombinant methioninase (o-rMETase), both alone and in combination with other agents. The present case is a 66-year-old patient who had a radical prostatectomy in 2019 with a Gleason score 3+3 and 3+4. The patient subsequently was treated with immunotherapy in 2021 and salvage proton-beam therapy in 2022, and subsequently treated only with o-rMETase and a low-methionine diet. The aim of the present study was to determine the long-term efficacy of methionine restriction on the patient's prostate cancer.

Case report: Starting in September 2022, the patient started methionine restriction with a low methionine-diet and o-rMETase, twice a day, after meals, at 250 units/dose. Since the start of methionine restriction, the patients' prostate-specific antigen (PSA) has remained stable, under 2 ng/ml. Positron emission tomography/computed tomography (PET/CT) and prostate specific membrane antigen (PSMA)-PET imaging indicated in September 2023 a right pelvic-side-wall metastatic lymph node that was stable when the PSMA-PET scan was repeated in March 2024, with the standardized uptake value (SUV) decreasing from 19.39 to 14.98. A very small possible metastatic external-iliac lymph node was detected in March 2024. Thus, the lymph-node metastases were stable and did not increase.

Conclusion: During the time the patient was on methionine restriction alone, effected by a low-methionine diet and o-rMETase, the metastatic prostate cancer did not progress. Further clinical studies of methionine restriction and metastatic prostate cancer are needed, including randomized clinical trials.

Background/aim: Atezolizumab, one of the anti-PD-L1 antibodies, targets PD-L1 expressed on cancer cells and antigen-presenting cells. This immune checkpoint inhibitor is now commonly used in combination with chemotherapy. The objectives of this study were to confirm the treatment outcomes of combined atezolizumab plus chemotherapy, and to identify prognostic factors, with a particular focus on the impact of the site of metastasis in real-world clinical practice.

Patients and methods: A retrospective review of clinical information on non-small cell lung cancer patients who received combined atezolizumab plus chemotherapy from May 2018 to August 2024 at our 11 hospitals was conducted.

Results: The 141 patients evaluated had a median progression-free survival of 8.0 months and a median overall survival of 19.0 months. Multivariate analyses showed that 'absence of liver metastases', 'absence of adrenal metastases', 'first-line combined atezolizumab plus chemotherapy', and 'good performance status' were associated with progression-free survival and overall survival. Immune-related adverse events were observed in 27.7% of patients, with grade 3 or higher in 9.9% of patients, and grade 5 in 2.1% of patients.

Conclusion: Efficacy and immune-related adverse events associated with the combination of atezolizumab and chemotherapy in non-small cell lung cancer patients were comparable to previous clinical trials. To ensure that appropriate patients receive the most effective treatment, it is important to identify detailed prognostic factors, including clinical information, such as the affected metastatic organs. Continued research and further accumulation of knowledge in this area are eagerly anticipated.

Background/aim: The incidence of biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, has been increasing worldwide. Approximately 70% of BTC patients have advanced disease at diagnosis, leading to a poor survival rate. Recent clinical trials have demonstrated that the addition of immune checkpoint inhibitors, such as durvalumab or pembrolizumab, to gemcitabine plus cisplatin chemotherapy significantly improves survival rates, making triple therapy the current standard for first-line treatment of BTC. Few models with predictive value exist for BTC. Lymphocyte-to-monocyte ratio (LMR) is a relatively new inflammation-related score and translational biomarker and has prognostic value for survival of patients with other cancers. This study assessed the prognostic value of LMR in patients with advanced BTC and analyzed the risk factors associated with overall survival (OS).

Patients and methods: This prospective study enrolled 75 patients with advanced BTC who were treated with gemcitabine-based chemotherapies at Aso Iizuka Hospital, Japan. The cutoff value of LMR for predicting 6-month survival was 3.27.

Results: OS was longer for patients with high LMR compared with low LMR (median 32.4 months and 8.6 months, respectively; p=0.0069). Multivariate analysis identified LMR >3.27 [hazard ratio (HR)=0.427, p=0.0339] and objective response rate (HR=0.210, p=0.0116) as independent factors associated with OS.

Conclusion: Despite some limitations, such as the single-center design and small sample size, the results of this study suggest a potential role for LMR in predicting survival outcomes for BTC patients treated with gemcitabine-based chemotherapies.

Background/aim: Karyopherin alpha 2 (KPNA2) has been reported to be associated with cancer aggressiveness and treatment resistance via transporting several cargo proteins into the nucleus, such as cancer-promoting E2F and DNA repair-related MRN complex. Recent studies have highlighted the KPNA2 functions in tumorigenesis and the progression of various cancers. However, the importance of KPNA2 expression has yet to be elucidated in clinical neuroblastoma patients. This study aimed to analyze the clinical impact of KPNA2 expression in neuroblastoma.

Materials and methods: KPNA2 expression in 81 resected neuroblastoma sections was examined using immuno-histochemical staining. The significance and prognostic value of tumoral KPNA2 expression were analyzed using our cohort and R2 database.

Results: The KPNA2 was expressed in the nucleus of neuroblastoma cells. The expression level of nuclear KPNA2 was not associated with clinicopathological factors in neuroblastoma. Among our cohort (n=81), non-radically resected neuroblastoma patients (n=37) with high KPNA2 expression had poorer prognoses than those with low KPNA2 expression. The R2 database analysis validated that the high KPNA2 expression was related to the poor prognosis in the large-scale neuroblastoma cohort.

Conclusion: KPNA2 expression evaluation in neuroblastoma is a promising indicator of prognosis in non-curative resected cases. KPNA2 targeting may be a promising therapeutic strategy against advanced neuroblastoma.

Background/aim: Chronic lymphocytic leukemia (CLL) is currently incurable. CLL is characterized by disordered DNA methylation. The aim of the present study was to target methylation with methionine restriction in a patient with progressive CLL.

Case report: Methionine restriction for the patient was achieved with a low-methionine vegan diet and oral recombinant methioninase (o-rMETase). The patient also received rituximab, once per week for four weeks, and acalabrutinib 100 mg, twice daily (bid) continuously. The patient's white blood cell count decreased by 95% from peak levels and extensive lymphadenopathy disappeared during combination treatment with o-rMETase, rituximab, and acalabrutinib.

Conclusion: The combination of methionine restriction and first-line chemotherapy resulted in an apparent complete response (CR) in a CLL patient, a rare event. The duration of the CR will be monitored, and additional CLL patients will be treated similarly in the future.

Background/aim: Although multiple treatments are available for metastatic castration-resistant prostate cancer, data to determine the optimal treatment sequence are limited. This study aimed to investigate the current status of drug therapy for castration-resistant prostate cancer and clarify the sequential treatment in actual clinical practice.

Patients and methods: This retrospective study included 425 patients diagnosed with castration-resistant prostate cancer at Showa University Hospital and affiliated hospitals between January 2014 and December 2021, who were treated with any of the following four drugs: novel androgen receptor signal inhibitors (abiraterone acetate and enzalutamide) and anticancer drugs (docetaxel and cabazitaxel). We investigated the actual treatment choices for castration-resistant prostate cancer, focusing on the order of administration of the four drugs. This analysis was visualized using a Sankey diagram.

Results: Regarding the number of drugs administered, most patients received one type of drug, with androgen receptor signal inhibitors being the most commonly administered (total, 179; enzalutamide, 139 and abiraterone acetate, 40). Enzalutamide was the most frequently selected first-line drug (58.4%). The most common sequence for second-line treatment was androgen receptor signal inhibitor-androgen receptor signal inhibitor (n=96), followed by androgen receptor signal inhibitor-docetaxel (n=85), docetaxel-androgen receptor signal inhibitor (n=59), and docetaxel-cabazitaxel (n=6).

Conclusion: Androgen receptor signal inhibitors is the most commonly used drug category for first-line treatment of castration-resistant prostate cancer, with enzalutamide being the most commonly used drug. Further investigations are required regarding patient background and prognosis.

Background/aim: The cachexia index (CXI) has been reported to be a useful indicator for predicting the prognosis of cancer patients. However, CXI calculation requires skeletal muscle index (SMI) measurements, which involves an analysis of computed tomography images using an imaging software program, which makes the calculation process highly complex and time-consuming. Recently, the modified cachexia index (mCXI), calculated using the urea-to-creatinine ratio (UCR) instead of SMI, has been reported to be a useful marker that is easier to calculate than CXI. This study aimed to evaluate the correlation between mCXI and the prognosis of patients with colorectal cancer (CRC).

Patients and methods: A total of 291 patients who underwent curative surgery for stage I-III CRC were enrolled. mCXI was calculated as the serum albumin concentration/neutrophil-to-lymphocyte ratio (NLR)/UCR. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value of the mCXI for predicting prognosis.

Results: The median mCXI was 0.089 (range=0.012-0.354). The ROC curve analysis revealed that the appropriate cut-off value for mCXI was 0.113. The low mCXI group had significantly shorter relapse-free and overall survival rates than the high mCXI group (p=0.030 and p=0.014, respectively).

Conclusion: mCXI, which does not require an image analysis, may be closely associated with prognosis in patients undergoing curative surgery for CRC.