Oncology最新文献

Introduction: This study aimed to evaluate the trends in safety signal detection of osimertinib compared with other epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) through volcano plot analysis, using data from the Japanese Adverse Drug Event Report (JADER) and FDA Adverse Event Reporting System (FAERS). The overall objective of this study was to identify the potential risks associated with osimertinib-induced adverse events.

Methods: Data were retrieved from the JADER (Q1 2004-Q1 2024) and FAERS (Q4 1997-Q2 2024) databases. The target drugs were osimertinib, gefitinib, erlotinib, and afatinib. Adverse event reports were standardized by converting all records in the database to the preferred terms of the International Classification of Diseases and subsequently mapping them to the high-level terms (HLTs) of the Medical Dictionary for Regulatory Activities. Volcano plots of odds ratios and z scores were generated to assess variations in detection trends between osimertinib and the abovementioned three EGFR-TKIs. The top 20 HLTs that demonstrated significant safety signals were computed and compared.

Results: The numbers of safety signals detected in the JADER for osimertinib compared to the aforementioned EGFR-TKIs following volcano plot analysis were 24, 20, and 16, whereas detected safety signals were 7, 43, and 14 in FAERS. In the JADER database, the most frequently reported adverse reactions for osimertinib included "poisoning and toxicity" and "heart failure." Conversely, in the FAERS database, the predominant adverse reactions were "death and sudden death" and "marrow depression and hypoplastic anemias."

Conclusion: This study confirmed an increased frequency of reports linking osimertinib to cardiotoxicity, bone marrow suppression, and anemia. However, interstitial pneumonia, previously considered a risk factor, was not identified. When evaluating risks influenced by racial and treatment-related factors, caution must be exercised regarding potential discrepancies between reported rates and true incidence.

Introduction: Among malignant brain tumors, glioblastoma (GB) is one of the most common. An early diagnosis would benefit the prognosis: in this regard, the search for sensitive and specific biomarkers is particularly active. In fact, liquid biopsy has been proposed by many researchers as a valid and repeatable method of studying GB. Among the biomarkers researched in blood patients, microRNAs (miRNAs) are among the most encouraging. The aim of our research was to select blood miRNAs overexpressed in GB patients to establish a reliable biomarker panel for pathology.

Methods: We studied blood expression of 14 miRNAs in 30 subjects with GB, before and after surgery, and 30 healthy controls.

Results: Statistical analysis allowed us to select a panel of 3 miRNAs (miR-340-5p, miR-369-3p, miR-486-5p) that are overexpressed in GB patients.

Conclusion: Our results showed that simultaneous measurement of circulating miR-340-5p, miR-369-3p, and miR-486-5p represents a promising biomarker for the diagnosis and follow-up of GB patients.

Introduction: Our study aimed to identify risk factors associated with the survival of gastric cancer patients with type 2 diabetes mellitus (T2DM) and create a risk-scoring system for predicting their survival probabilities.

Methods: We gathered data from 1,912 individuals with both gastric cancer and T2DM from the Hong Kong Hospital Authority Data Collaboration Laboratory (HADCL), spanning from 2000 to 2020. We used conventional Cox proportional hazards regression and tree-based machine learning algorithms to construct models for prognosis risk prediction. In the best-performing model, risk factors were identified using SHAP (Shapley Additive Explanations) analysis, and the AutoScore-Survival package was used to develop a risk-scoring system.

Results: Our findings indicate that older age at cancer diagnosis, longer duration of T2DM, higher body mass index (BMI), central obesity, lower levels of high-density lipoprotein cholesterol, and reduced serum potassium are associated with poorer prognosis for gastric cancer in patients with T2DM. The Random Survival Forests (RSF) model exhibited the best performance, achieving an AUC of 0.870 and a concordance index of 0.78. Additionally, we developed two risk-scoring systems using predefined and tuned models, which yielded C-indices of 0.672 and 0.654, respectively, in the test set.

Conclusion: This study enhances our understanding of gastric cancer prognosis in patients with T2DM by identifying significant risk factors and developing risk-scoring systems. Further research is needed to elucidate the underlying mechanisms of these risk factors and to validate the risk-scoring systems in clinical settings.

Background: Recurrent laryngeal nerve (RLN) palsy (RLNP) is not uncommon after thyroid surgery and can be debilitating. This is a retrospective cohort analysis of outcomes in patients with RLNP post-thyroidectomy for differentiated thyroid malignancy.

Method: Clinicopathological details as well as outcomes of thyroidectomies for differentiated thyroid cancer in 862 patients performed over a period of 22 years (2001-2023) for nerve palsy were collected. The patients were stratified into two groups based on whether the RLN was amputated or preserved.

Results: Of the 1,520 nerves in 862 patients at risk during thyroidectomy, a total of 71 (8.2%) (20 M:51 F) patients, with a median age of 54 (range: 19-83), suffered RLNP, which was temporary in 14 (1.6%), unilateral in 51 (5.9%), and bilateral in 6 (0.7%) patients. The RLN was amputated in 31 of 62 patients (50%). In 29 of 71 (41%) patients, the nerve was intentionally sacrificed due to gross disease infiltration while the RLN was inadvertently severed during dissection in 2 (3%) patients. Among cases with RLN transection, only five underwent primary repair or ansa cervicalis to RLN anastomosis. The only factor associated with amputation of the RLN was a larger tumour size (40.4 vs. 24.7 mm, p = 0.007). Preservation of voice quality was higher in the shave group in comparison to the amputation group (93.5% vs. 71.0%, p = 0.0426).

Conclusion: Preservation of nerve or reconstruction in transectional injuries should be considered where possible to improve voice outcomes except in cases when the laryngotracheal complex is involved.

Introduction: With expanding indications for chimeric antigen receptor T-cell (CAR-T) therapy, more patients with diverse clinical profiles are receiving treatment, some of whom may not have been eligible to enroll on the pivotal clinical trials. The impact of preexisting cardiovascular diseases (CVDs) on the outcomes of CAR-T recipients remains understudied.

Methods: Our study aimed to evaluate the impact of preexisting CVD on in-hospital outcomes among patients who received CAR-T therapy using the Nationwide Readmissions Database (NRD) from 2018 to 2020. We analyzed patients aged ≥18 and compared outcomes between those with and without preexisting CVD, utilizing sampling weights for national estimates.

Results: After weighting, the cohort included 4,950 patients: 2,312 (46.7%) and 2,638 (53.3%) with and without preexisting CV, respectively. Patients with preexisting CVD experienced significantly higher rates of acute heart failure (2.9% vs. 0.7%; p = 0.01), myocardial infarction (2.2% vs. 0.9%; p < 0.01), cerebrovascular accidents (1.4% vs. 0.7%; p < 0.01), and acute kidney injury (19.2% vs. 13.3%; p < 0.01). Rates of cardiogenic shock, cardiac arrest, and pulmonary embolism were comparable between these 2 groups. Multivariate analysis showed preexisting CVD was not associated with increased odds of early mortality {adjusted odd ratios (aOR) = 1.01 (95% confidence intervals [CIs], 0.69-1.49), p = 0.95}, prolonged index hospitalization (aOR = 0.94 [95% CI, 0.64-1.36], p = 0.73), non-home discharge (aOR 1.04 [95% CI, 0.79-1.38], p = 0.77), and 30-day readmission (aOR 0.99 [95% CI, 0.81-1.20], p = 0.91).

Conclusion: Although there were significant differences in acute complications, our study reinforces that the presence of CVD does not adversely affect early mortality rates.

Introduction: Hepsin is a type 2 transmembrane serine protease, primarily located on the cell membrane, which can degrade the extracellular matrix and modify connections between cells and the extracellular matrix. Given these features, hepsin is thought to play a role in cancer invasion and metastasis. While studied in various other cancers, hepsin's role in pancreatic cancer remains unexamined.

Methods: Our study included 223 patients diagnosed with pancreatic ductal adenocarcinoma. Among these, 66 received neoadjuvant therapy and these were analyzed separately. Tissue microarrays and immunohistochemistry were used to assess the expression of hepsin in pancreatic ductal adenocarcinoma tissue. Hepsin expression intensity, ranging from negative to strong, was evaluated against clinicopathological parameters, including age at surgery, sex, T-stage, N-stage, tumor grade, perivascular and perineural invasion, CA19-9 levels, ASA class, stage, and, in the neoadjuvant-treated group, response to neoadjuvant therapy.

Results: A strong hepsin expression was observed in 105 (67%) patients who did not receive neoadjuvant therapy, while 27 (42%) neoadjuvant-treated patients exhibited a strong expression. Hepsin expression did not associate with survival in either group. In the neoadjuvant-treated group, a strong positivity was, however, associated with a lower T-stage (p = 0.005) and higher N-stage (p = 0.048). Among those receiving gemcitabine-based chemotherapy, a weaker hepsin expression was associated with a better treatment response (p = 0.011).

Conclusions: A low hepsin expression following neoadjuvant therapy is associated with a better treatment response among those receiving gemcitabine-based treatment. Thus, hepsin does not appear to influence prognosis in pancreatic cancer patients, regardless of whether they received neoadjuvant therapy or not.

Background: Patients with biliary tract cancers (BTC) often require antibiotic therapy before starting systemic treatment that includes an immune checkpoint inhibitor. This study aims to evaluate the prognostic impact of antibiotic therapy administered in the 15 days prior to the start of chemoimmunotherapy in patients with BTC.

Material and methods: The study population included patients with metastatic or locally advanced BTC from western and eastern populations treated with first-line chemoimmunotherapy. The aim of the study is to evaluate the impact of antibiotic therapy in the 15 days prior to starting oncological treatment (AT population) compared to patients who did not receive antibiotic therapy (NAT). Univariate and multivariate analyses were used to evaluate predictive factors for overall survival (OS) and progression free survival (PFS) while prognostic factors were analyzed by univariate and multivariate analysis using Cox regression model.

Results: 666 patients were enrolled in the study: 93 (14%) in AT cohort and 573 (86%) in NAT cohort. In the AT population, the incidence of cholangitis (p = 0.0017), ALT elevation (p = 0.0009), fever (p = 0.0021), decreased appetite (p = 0.0007), itching (p = 0.0081), and rash (p = 0.012) was significantly higher compared to the NAT. The median OS was 15.9 months (95% CI 13.8 - 18.3) in NAT cohort vs 10.1 months (95% CI 7.9 - 12.4) in AT cohort (NAT vs AT, HR 0.43,95% CI 0.27 - 0.70-15.6 p=0.0006) while median PFS was 8.5 months in NAT cohort vs 5.4 months in AT cohort (NAT vs AT, HR 0.49 ,95% CI 0.34 - 0.71 p=0.0001). Multivariate analysis confirmed the prognostic role of antibiotic for OS and PFS. Finally, NAT cohort showed better overall response rate compared with AT cohort (31.4% vs 20.4 %, p=0.03).

Conclusions: The use of antibiotic therapy in the 15 days prior to starting chemoimmunotherapy is an independent unfavorable prognostic factor for survival in our cohort of patients with advanced BTC treated with cisplatin, gemcitabine and durvalumab.

Introduction: Systemic therapy options for hepatocellular carcinoma (HCC) have rapidly expanded, transforming the treatment landscape. However, real-world changes in treatment choices remain unclear. This study aimed to determine the current treatment choices for HCC in Japan, considering age and liver functional reserves.

Methods: We conducted an interrupted time series analysis using electronic medical records in Japan to assess the overall changes in the proportions of systemic therapy among the initial treatments for HCC following the approval of lenvatinib in 2018 and atezolizumab plus bevacizumab (atezo/bev) in 2020, stratified by age and modified albumin-bilirubin (mALBI) grade. This study included patients who were diagnosed with HCC between 2015 and 2022. We also assessed 2-year survival rates.

Results: In the interrupted time series analysis, the proportions of systemic therapy among the initial treatments for HCC increased by 3.96% (95% confidence interval: 2.75, 5.17, p < 0.001) following lenvatinib approval, with a 1.00% (0.45, 1.55, p = 0.002) slope change per 6 months. There was a 4.27% (1.69, 6.86, p = 0.004) increase in systemic therapy use following atezo/bev approval and a 0.27% (-0.66, 1.20, p = 0.53) slope change. In age subgroups with a cutoff of 75 years, the largest increase in systemic therapy use was 6.94% (4.46, 9.42) in the elderly group following atezo/bev approval (p = 0.189). Increases in systemic therapy use following lenvatinib approval in patients with mALBI grades 2b or 3 and 1 or 2 were 10.0% (6.70, 13.42) and 0.80% (-1.16, 2.77), respectively (p < 0.001). There was no apparent change in the overall 2-year survival or in any subgroup before and after approval.

Conclusion: Newly developed drugs for HCC would expand the population for systemic therapy. The optimal population for systemic therapy should be explored based on long-term survival considering age and liver functional reserve heterogeneity.

Aims: Sustained virological response (SVR) is a favorable prognostic factor for patients with hepatocellular carcinoma (HCC) caused by hepatitis C virus (HCV) treated curatively. This study aimed to evaluate the impact of SVR on atezolizumab plus bevacizumab (Atez/Bev) therapy for unresectable HCC (uHCC) caused by HCV.

Methods: A retrospective analysis of 364 uHCC patients treated with Atez/Bev (September 2020-April 2025) and divided into SVR (n = 284) and non-SVR (n = 80) groups was performed, with clinical characteristics, prognosis, and adverse events compared.

Results: There were no significant differences between the groups for age, sex, platelet count, AFP, or BCLC stage. However, the SVR group showed a significantly better ALBI score (-2.50 vs. -2.16) and lower AST (33 vs. 57 IU/L) and ALT (23 vs. 40 IU/L) levels (p < 0.01). Median progression-free survival (PFS) was 7.1 months in the SVR group and 6.1 months in the non-SVR group (p = 0.443), and median overall survival (OS) was 20.9 months in the SVR group and 18.9 months in the non-SVR group, with no significant differences between the groups (p = 0.560). Following IPW adjustment for factors related to OS, there was no significant difference regarding PFS (p = 0.921) and OS (p = 0.927). Multivariate analysis identified age ≥75 years and poor hepatic function (mALBI grade 2b/3) as independent predictors of poor OS; SVR status was not an independent factor. Changes in ALBI and Child-Pugh scores over time were not significantly different between the groups. In the non-SVR group, adverse events were more common as compared to the SVR group, including liver dysfunction (27.5% vs. 13.0%, p < 0.001) and edema/ascites (12.5% vs. 9.2%, p = 0.015).

Conclusions: Although SVR was not independently associated with better survival, patients with SVR had preserved liver function and experienced fewer adverse events. These factors may indirectly support improved tolerability and therapeutic options during Atez/Bev therapy for HCV-related uHCC.

Introduction: The DESTINY-B01 trial led to trastuzumab deruxtecan (T-DXd) approval for human epidermal growth factor receptor-2 (HER2+) metastatic breast cancers (mBCs), with efficacy further confirmed by DESTINY-B03, demonstrating improved progression-free and overall survival versus trastuzumab emtansine. Despite its efficacy, T-DXd had notable adverse events (AEs), including interstitial lung disease, necessitating real-world studies on safety and tolerability. Findings from such studies may help guide treatment selection and inform risk-benefit discussion in routine clinical practice.

Methods: A real-world cohort study evaluated the safety and tolerability of T-DXd in patients with HER2+ mBC. De-identified patient data, tumor characteristics, AEs, dose modifications, and discontinuation rates due to AEs were analyzed.

Results: Between January 2020 and June 2024, 85 predominantly non-Hispanic white patients with a median age of 57 years were treated. Notably, 17.6% had an ECOG performance status of 2-3, 69.4% had 1-2 prior metastatic treatments, 94% had visceral involvement, and most received primary prophylaxis with dexamethasone and palonosetron. Approximately 29.4% initiated treatment at a reduced dose; 40% required further dose reductions, primarily due to fatigue (9.4%). Permanent discontinuation due to AEs occurred in 10.6%. Common AEs included fatigue (95.3%), alopecia (14.1%), and peripheral neuropathy (14.1%). Grade ≥3 AEs were infrequent and included neutropenia (10.6%), elevated aspartate aminotransferase (2.4%), elevated alkaline phosphatase (2.4%), and interstitial lung disease (1.2%). No grade 5 events were observed.

Conclusion: T-DXd demonstrated acceptable tolerability with manageable AEs in real-world patients with HER2+ mBC, aligning with clinical trial outcomes and supporting its continued use in clinical practice.