Oncology最新文献

Background：The incidence of lung cancer remains high worldwide and is still the leading cause of cancer-related deaths globally.The primary reason for this is that the vast majority of patients are diagnosed only when the disease has progressed to an advanced stage or metastasized.Therefore,early diagnosis of lung cancer is crucial.Approximately 85% of lung cancers are non-small cell lung cancer (NSCLC),As a type of non-small cell lung cancer (NSCLC), lung adenocarcinoma is more prone to distant metastasis and has a poorer prognosis.It is often primarily treated with immunotherapy.Currently, immunotherapy mainly focuses on T cells,However, with the deepening of research, plasma cells, which have long been considered non-essential in anti-tumor responses, have been increasingly recognized for their critical role. Methods：This study integrates data from TCGA, Tumor Immune Single-cell Hub 2, and 10X databases, focusing on plasma cells. Through clustering analysis and LASSO regression analysis, it aims to establish a predictive model for high-risk LUAD patients and further explore the relationship between the risk model and immune cells, with the goal of providing potential predictions for the efficacy of immunotherapy for patients.Additionally, we conducted drug sensitivity analysis and immune checkpoint analysis to identify drugs with potential benefits for the clinical management of high-risk patients.At the same time, we performed further immune checkpoint analysis to identify potential therapeutic targets for LUAD.Results：By integrating the TCGA, Tumor Immune Single-cell Hub 2, and 10X databases, and focusing on plasma cells through clustering analysis and LASSO regression analysis, we established a predictive model for high-risk LUAD patients involving four feature genes: BEX5, CASP10, EPSTI1, and LY9. The ROC and results demonstrate that our model has strong predictive performance. Additionally, we found that the risk model is closely related to immune cells, providing potential for predicting the efficacy of immunotherapy for patients. Subsequently, we conducted drug sensitivity analysis and immune checkpoint analysis, revealing that the majority of drugs are more sensitive to low-risk patients, while ABT-888, AS601245, and CCT007093 may have greater potential clinical benefits for high-risk patients. Immune checkpoint analysis showed significant differences in the expression of ADORA2A, BTLA, CD276, CD27, CD28, CD40LG, CD48, and TNFRSF14 between high-risk and low-risk patient groups, suggesting their potential as therapeutic targets for LUAD..

Introduction: The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib is associated with a high incidence of neutropenia. Treatment continuation using the standard dosing schedule (3 consecutive weeks of oral administration followed by 1-week off-treatment: 3/1 schedule) can be difficult and other dosing schedules have been previously adopted. We aimed to investigate whether alternative dosing schedules can be used effectively to continue palbociclib.

Methods: This study included all patients who received palbociclib for hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (HR+/HER2-MBC) at Ogaki Municipal Hospital between January 2018 and November 2023. Reasons for treatment discontinuation, changes in treatment administration, treatment duration, relative dose intensity (RDI), overall response rate (ORR), clinical benefit rate (CBR), and adverse events were retrospectively investigated using electronic medical records.

Results: On November 30, 2023 (a data censor date), patients who discontinued or continued palbociclib on the 3/1 schedule were classified into the 3/1 schedule group (n=20), and those who started a 3/1 schedule (partly on a 2/2 schedule) and then switched to the 3/2 schedule or the 2/2 schedule (2 consecutive weeks of oral administration followed by 2 weeks off) were classified into the 3/2 (n=10) or 2/2 schedule groups (n=18), respectively. For the 3/1, 3/2, and 2/2 schedule groups, respectively, the median treatment duration was 255.5, 1253.0, and 923.0 days (p=0.0013), the median RDI (%) was 71.0%, 69.2%, and 40.8% (p<0.001), and the ORR was 15.0%, 80.0%, and 50.0% (p=0.002), while the CBR was 55.0%, 100%, and 72.2% (p=0.028).

Conclusion: Dosing schedules other than the standard 3/1 schedule can be used to continue palbociclib with HR+/HER2-MBC while ensuring therapeutic efficacy. Alternative dosing schedules look promising and need further research (preferably, prospective studies) with a larger sample size and longer follow-up to validate treatment efficacy.

Introduction: Presence of macroscopic portal vein thrombosis (PVT) in patients with hepatocellular carcinoma (HCC) has been found to be a major poor prognosis characteristic.

Aims: To examine patients with PVT for their clinical characteristics and factors related to both PVT and to survival.

Methods: A large HCC database containing 1094 patients with PVT and 2513 patients without PVT was examined. Patients had routine baseline serum liver parameters and alpha-fetoprotein (AFP) levels measured; radiological assessment of maximum tumor diameter (MTD), tumor number, presence of macroscopic portal vein thrombosis, plus survival.

Results: The percent of patients with PVT increased with increase in both MTD and serum AFP levels and liver parameter levels were worse in patients with PVT than without it. A logistic regression model showed that the combination of MTD>5cm plus AFP >100 IU/mL plus albumin <3.5 g/dL had an odds ratio of 10.988 for the presence of PVT. Normal serum albumin levels significantly reduced the hazard ratio for death in a Cox proportional hazard model and were associated with decreased liver failure.

Conclusion: Logistic regression showed the significance of MTD, AFP and albumin on presence of PVT and the Cox model highlighted the importance of albumin levels in decreasing death.

Introduction: Cisplatin-based highly emetogenic chemotherapy is recommended in combination with neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytriptamine-3-receptor antagonist (5HT3RA), dexamethasone (DEX), and olanzapine. However, olanzapine is contraindicated in patients with pre-existing diabetes mellitus (DM). This study compared the efficacy of a triplet antiemetic regimen (NK1RA, 5HT3RA, and DEX) in patients with and without pre-existing DM treated with cisplatin-based chemotherapy.

Methods: This retrospective study enrolled patients with esophageal cancer with and without pre-existing DM who received fluorouracil and cisplatin (FP) combination chemotherapy as initial therapy with a triplet antiemetic regimen for antiemetic prophylaxis. This data was compared using propensity score matching (PSM). The primary endpoint was the complete response (CR) rate during the first cycle, which was defined as no emetic episodes and no rescue medication use during the overall period (0-120 h). The CR rate was analyzed using univariate and multivariate logistic regression, including previously reported risk factors. The significance level was set at 5%.

Results: Out of 210 eligible patients, 39 and 39 were patients with DM and non-DM patients after PSM, respectively. The CR rate measured by multivariate analysis during the overall period with DM and non-DM was 56.4% and 41.0% (adjusted odds ratio of 0.566 [95% confidence intervals: 0.209-1.536], P = 0.264), respectively. The CR rate during the delayed period (24-120 h) with DM and non-DM patients was 84.6% and 46.2% (P = 0.002), respectively.

Conclusions: A triplet antiemetic regimen in patients with esophageal cancer with pre-existing DM might be more effective in delayed period compared to non-DM patients.

Introduction: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a retrospective analysis of its first-line treatment outcomes.

Methods: We included patients with unresectable, locally advanced, or metastatic BTC treated with cisplatin, gemcitabine plus durvalumab. The primary endpoint was overall survival (OS).

Results: 33 patients were enrolled. Median OS was NR and median PFS was 7.6 months, after a median follow up of 13.5 months. The investigator-assessed overall response rate was 34.5 %, with stable disease in 53.0 % of patients. High baseline CEA levels were associated with poor survival. Any grade adverse events (AEs) occurred in 97 % of patients. Immune-related AEs (irAEs) occurred in 16 % (grade >2: 6 %). Presence of TP53 mutation was related to a worse OS, conversely the presence of ARID1A genomic alteration was related to a better PFS. A tendence toward a better OS was found for BRCAness patients which did not reach the statistical significance. On the other hand, BRCAness patients showed significantly higher PFS compared to no BRCAness patients Conclusion: This real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.

Introduction Gastric cancer remains one of the leading causes of cancer-related mortality worldwide, with lymph node metastasis (LNM) being an independent prognostic factor. However, there are still challenges in the pathological diagnosis of LNM in gastric cancer (GC). The aim of this meta-analysis is to systematically evaluate the accuracy of artificial intelligence (AI) in detecting LNM in GC from whole-slide pathological images.. Methods As of March 24, 2024, a comprehensive search for studies on the pathological diagnosis of GC LNM AI was performed in the databases of PubMed, Web of Science, Cochrane Library, and CNKI. Meta-analysis of the included data was performed using Meta-Disc 1.4, Review Manager 5.4, and Stata SE 17.0 software to calculate diagnostic metrics such as overall sensitivity and specificity. The overall diagnostic performance of the AI was assessed. Meta-regression analysis explored sources of heterogeneity. Results A total of 7 articles involving 1,669 GC patients were included. The analysis showed that AI had a sensitivity of 0.90 (95% CI: 0.84-0.94) and a specificity of 0.95 (95% CI: 0.91-0.98) for the diagnosis of GC LNM, with significant heterogeneity across studies. The area under the curve was 0.97, indicating an excellent diagnostic value. Meta-regression analysis showed that the sample size and the number of study centers contributed to the heterogeneity. Conclusion AI for diagnosing LNM in GC from whole-slide pathological images demonstrates high accuracy, offering significant clinical implications for improving diagnosis and treatment strategies.

Introduction: The effectiveness and tolerability of triple therapy, which combines regorafenib, a programmed death 1 (PD-1) inhibitor, and transarterial chemoembolization (TACE), were compared to dual therapy consisting of regorafenib and a PD-1 inhibitor in patients with advanced hepatocellular carcinoma (HCC).

Methods: A retrospective analysis was conducted on patients with advanced HCC who underwent second-line therapy from March 2019 to June 2022 at multiple centers. Patients were stratified into two groups: dual therapy (comprising regorafenib and a PD-1 inhibitor) and triple therapy (consisting of regorafenib, a PD-1 inhibitor, and TACE). Propensity score matching (PSM) was used to control for potential confounding variables.

Results: After PSM, 112 eligible patients were included, with 56 in the triple therapy group and 56 in the dual therapy group. Median overall survival (OS) was significantly longer in the triple therapy group (15.4 vs. 8.9 months, p < 0.001), as was median progression-free survival (PFS) (6.8 vs. 3.3 months, p < 0.001). The objective response rate (ORR) (37.5% vs. 5.4%, p < 0.001) and disease control rate (DCR) (73.2% vs. 44.6%, p = 0.002) were significantly higher in the triple therapy group compared to the dual therapy group. The incidence and severity of adverse events were similar between the two groups.

Conclusion: Triple therapy demonstrated superior survival benefits compared to dual therapy in patients with advanced HCC. Additionally, the safety profiles of the two treatment regimens were comparable.

Background Oncological therapy is based on multidimensional therapy protocols. The requirements for standardized protocols and digitation are high. These protocols are created through several complex development stages to ensure standardized recording. The process involves analyzing original publications published in international journals and extracting key content. Standardized supportive therapy is then added, and compatibility with current guidelines and quality controls is checked. Summary The Onkopti® website is based on the WordPress content management system and provides protocols in a variety of formats, generated through the use of a relational SQL database (www.onkopti.de, www.onkopti.com, www.oncopti.com). It is continuously updated to include new therapeutic developments or changes to standard therapy. The protocols are stored in a relational database and can be exported to various application systems via a standardized XML format or other formats. The website and protocols are available in both German and English. As of August, 2024, there are over 2600 protocols for parenteral and oral therapies for all oncological specialties.. Key Messages The digitalization of protocol selection, prescription, pharmacy preparation, hospital or practice information system documentation, billing, and prescription creation can accelerate, standardize, and streamline these processes. This optimization can significantly reduce personnel costs, resulting in cost savings and improved quality.

Introduction: Conflicting evidence exists regarding the concurrent use of cyclin-dependent kinase (CDK) 4/6 inhibitors and proton pump inhibitors (PPIs) in the treatment of breast cancer. This study aimed to investigate whether PPI use interferes with the efficacy of CDK4/6 inhibitors.

Methods: This retrospective, multicenter, real-world study included 205 patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Patient data were collected from January 2020 to August 2023. Patients who received either ribociclib or palbociclib, with or without a PPI, were included. Median progression-free survival (mPFS) was estimated using the Kaplan-Meier method, and factors associated with mPFS were analyzed using Cox regression.

Results: Among the patients, 100 received palbociclib and 105 received ribociclib. In the palbociclib group, 40 patients (40%) used a PPI, and 60 (60%) did not. The mPFS was 16.1 months for patients with a PPI versus 22.2 months for those without (p=0.26). In the ribociclib group, 44 patients used a PPI and 61 did not use a PPI. The median PFS was comparable between patients receiving PPIs and those not receiving PPIs. (19.3 months and 20.7 months, respectively). Poor PFS was associated with liver metastasis, brain metastasis, and high Ki-67.

Conclusion: Concomitant use of PPIs with ribociclib or palbociclib did not affect the efficacy of either CDK4/6 inhibitor. PPIs can be administered alongside these medications when clinically indicated.

Introduction: Understanding the metastatic patterns is crucial for the treatment of malignancies. This study aimed to identify the characteristic organ metastases of primary malignancies, including rare malignancies, and classify them according to their metastatic patterns.

Methods: We extracted data on primary malignancies and organ metastases from the Annual of Pathological Autopsy Cases in Japan recorded in 1993-2021. Autopsy findings of the primary and metastatic organs in patients with malignancy were recorded on an organ-by-organ basis. The metastatic frequency (number of metastases per autopsy) and the proportion (percentage of organs with metastases out of the total in a primary malignancy) for 48 organ metastasis sites across 76 primary malignancies were calculated. Metastatic patterns were classified into hierarchical and non-hierarchical clustering classifications based on the standard proportion of organ metastases.

Results: A total of 332,195 autopsy cases and 810,206 organ metastases were analyzed. The metastatic frequency of all malignancies was 2.44. Malignancies of the placenta, eye, and ovary showed a higher propensity for metastasis, whereas central nervous system malignancies showed a lower tendency. Metastasis site was a characteristic of each malignancy, with a particularly high proportion of lung metastasis in parathyroid malignancy and bone metastasis in prostate malignancy. In the hierarchical and non-hierarchical cluster methods, brain, lung, liver, bone, peritoneum, and hematolymphoid organ were key metastatic sites, and this factor divided primary malignancies into seven categories. The unweighted kappa coefficient comparing the two classification methods was 0.84 (95% confidence interval: 0.75-0.93). The proportion of metastatic organs was influenced by anatomical location and/or organ specificity of the primary malignancies.

Conclusion: Our study provides a comprehensive overview of the patterns and frequencies of metastatic organ sites associated with 76 primary malignancies. Our findings will provide useful information for future research and clinical practice.