Oncology Research and Treatment最新文献

Introduction: This study aimed to evaluate the effectiveness of GPT-4o, with and without Retrieval-Augmented Generation (RAG), in responding to soft tissue sarcoma (STS)-related queries.

Methods: The study used a 20-question dataset derived from clinical scenarios related to adult STS. The responses were generated by GPT-4o with and without the RAG approach. The RAG system incorporated the English version of German evidence-based S3 guidelines through an embedding-based retrieval system. Two sarcoma experts evaluated the responses for accuracy, comprehensiveness, and safety using a Likert scale. Statistical analyses were conducted to compare the performances.

Results: GPT-4o with RAG outperformed the model without RAG across all evaluated areas (p<0.05). GPT-4o without RAG had a 40% error rate, which was reduced to 10% by the RAG approach. In 90% of the questions, the pages with the relevant information that addressed the questions were correctly cited using the retrieval system.

Conclusion: The RAG approach significantly enhanced the performance of GPT-4o in answering STS-related questions. However, the model still produced incorrect responses in certain complex scenarios. GPT-4o, even with RAG, should be used cautiously in clinical settings, particularly for rare diseases like sarcoma. Human expertise remains irreplaceable in medical decision-making.

Introduction: The COVID-19 pandemic has impacted the treatment of prostate cancer (PCa). The study examines any predictions that could point to future models.

Methods: Two interrupted time series analyses were conducted: one for the pre-COVID period (January 2017 to December 2019) and another for the post-COVID period during 2022. Information on age, total prostate-specific antigen (PSA), abnormal digital rectal exam (DRE), prostate volume (PV), previous negative biopsy, number of positive biopsies, Gleason score, and biopsy outcome were collected for all patients. The categories for the results were no cancer, insignificant, low and intermediate, high-risk, and very high-risk PCa. Using a generalized linear model (GLM), the outcomes are modeled. The area under the curve (AUC) and accuracy were used to assess how well multi-class predictions performed.

Results: 244 patients who had biopsies following the COVID-19 pandemic and 832 patients who had biopsies before the pandemic were compared. The accuracy of the GLM model was only 0.635. The AUC for category no cancer, low and intermediate-risk, and very high-risk patients was 0.821, 0.716, and 0.926. With scaled relevance values, PSA was the most critical test. The two features that significantly influenced the treatment model prediction for PCa were biopsy PSA level and DRE, respectively.

Conclusion: Advanced age and a very high-risk group appear to have a detrimental impact on the results of biopsies conducted after the first wave of the COVID-19 era. At the same time, PSA levels and abnormal DRE are the most significant predictors in GLM.

Introduction: Epidural anesthesia is a standard procedure to mitigate pain during surgery for endometrial cancer (EC). Little data exist about the influence of epidural anesthesia on the oncological outcome in elderly patients with EC. This retrospective study aims to investigate potential correlations between epidural anesthesia and cancer recurrence in patients with EC.

Methods: We screened the medical records of patients ≥ 60 years treated surgically for EC at the University Medical Center Mainz between January 2008 and December 2019. All women underwent general anesthesia (GA) alone or combined with epidural anesthesia (EGA). Cox regression, the Kaplan-Meier method and propensity score matching were used to analyze the prognostic influence of the anesthesiologic regime on survival.

Results: A total of 152 women with EC were included. 29 patients (19.1%) formed the EGA cohort. The median time of follow-up (FU) was 31 months [interquartile range (IQR): 8-67.5]. The EGA cohort showed more in-hospital complications (27.6 vs. 8.9%; p=0.006), especially thromboembolic events (3 vs. 0 events; p=0.006), as well as a longer hospital stay (11 (IQR: 8-13) vs. 7 (IQR: 4-9) days; p <0.001). 26 patients (17.1%) developed a recurrence in the follow-up at a median of 13 months [IQR: 7.75-29.5]. 32 patients died during FU (21.1%). The EGA cohort showed higher FIGO stages and a higher histological grading than the GA cohort. In Kaplan-Meier analysis, EGA showed a significantly reduced 5-year recurrence-free survival (RFS) (36.5% vs. 72.6%, p<0.001) and overall survival (OS) (58.6% vs. 79.9%, p=0.008). However, in multivariate Cox regression analysis including FIGO stages and histological grading, EGA did not influence RFS (HR: 2.02; 95%-CI [0.99-4.12], p=0.054), and OS (HR: 1.03; 95%-CI [0.40-2.66], p=0.951). This was backed up by the propensity score matched analysis for survival (RFS: p=0.604, OS: p=0.86).

Conclusion: Considering risk factors, epidural anesthesia in combination with GA did not differ in recurrence-free and overall survival compared to GA. Prospective randomized trials are warranted in order to further evaluate this topic.

Background: Current breast cancer (BC) surveillance is limited to the detection of local, locoregional or contralateral recurrence. This is based on two outdated studies from the 1990s and ignores current evidence on liquid biopsies, particularly circulating tumor DNA (ctDNA).

Summary: ctDNA has been shown to be a reliable prognostic biomarker in early BC surveillance. It can be detected using a tumor-informed or a tumor-agnostic approach. However, conclusive evidence for a survival benefit from ctDNA-guided follow-up, as needed for a paradigm shift in BC surveillance, is still lacking. According to current studies, the lead time, i.e. the time from biomarker detection to clinically overt relapse, can be up to several months. This stage of MRD (minimal or molecular residual disease) offers a new therapeutic window, and, currently, several studies are evaluating the efficacy of treatments initiated within this therapeutic window, based on a positive biomarker finding. Liquid biopsy might also open up the possibility of de-escalating therapy in patients with a negative biomarker result.

Background: Adoptive cellular therapy (ACT) is a promising treatment approach aiming at enhancing T cell antitumor immune response. ACT includes tumor-infiltrating lymphocytes (TILs), chimeric antigen receptor (CAR) and T-cell receptor (TCR) gene-modified T cells. Despite a milestone achievement with CAR-T cells in hematopoietic malignancies, ACT has shown modest clinical responses in refractory solid cancers and durable responses remain limited to a minor fraction of patients.

Summary: In this review, we highlight major advances, limitations and current developments of T cell therapies for solid cancers. We discuss emerging promising strategies as next-generation ACT, exploring local delivery routes to maximise efficacy and improve safety, integrating predictive biomarkers to optimize selection of patients who most likely would benefit from ACT, using combination therapy to overcome the immunosuppressive tumor microenvironment, targeting multiple tumor antigen to avoid tumor antigen escape, selection of the most potent T cell product to overcome T cell dysfunction and incorporating cutting edge new technologies, such as gene-editing to further improve anti-tumor T cell functions and reduce therapy-related toxicity.

Key messages: Advances made in ACT trials have move the field of immunotherapy for refractory solid cancers to a new stage, by constantly incorporating new strategies to develop next-generation therapies designed to enhance efficacy and improve safety and to allow a broaden access to a large numbers of patients.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a challenging malignancy and precision oncology treatment options may improve patient outcomes. Next-generation sequencing (NGS) is an established tool that enables multi-gene panel analysis.

Methods: This NGS tissue-based analysis, conducted at a German pancreatic cancer center, included 128 patients between January 2016 and January 2021.

Results: A targetable lesion was detected in 15.6% of patients. BRCA1/2 mutations were identified in 16 patients, of whom 13 had germline mutations; eight of these patients received Olaparib. In 41.4% of patients, homologous recombination repair (HRR) genes were affected. Two cases of ATP1B1-NRG1 fusions and seven cases of dMMR tumors were found, leading to individualized treatment. KRAS mutations were present in 70.3%, and TP53 mutations in 63.3%. A total of 80.5% of patients received platinum-based chemotherapy, predominantly FOLFIRINOX.

Conclusion: The high frequency of targetable alterations in our cohort underscores upfront NGS testing in PDAC. Younger patients, those with a positive FH and KRAS WT patients should be of particular interest.

Introduction: Although different risk factors for oxaliplatin-associated chronic peripheral neuropathy have been identified and the predictive value of neuroinflammatory cytokines has often been emphasized, a clearly accepted predictive biomarker with economical, reproducible, and easily accessible properties has not yet been identified. In this study, we aimed to determine the relationship between serum uric level measured at the time of diagnosis and oxaliplatin-related peripheral neuropathy, based on literature information on the relationship between diabetic neuropathy and serum uric acid level.

Methods: In the study, 166 patients with colon adenocarcinoma, who were clinically thought to have grade 1-2 neuropathy in their follow-up after completing the adjuvant mFOLFOX6 regimen without dose reduction for 6 months, were grouped as those with or without peripheral neuropathy according to electromyography results. Demographic, clinical, laboratory and treatment-related characteristics, as well as serum uric acid levels at diagnosis, were determined as study variables and the groups were compared. Based on the presence of peripheral neuropathy, an ROC curve was drawn for serum uric acid level, cut-off was determined and multivariable logistic (binary) regression analysis was also applied to determine independent risk factors that may affect peripheral neuropathy. If the P value was below 0.05, it was considered statistically significant.

Results: It was determined that 29% of the patients (n = 48) had peripheral neuropathy proven by electromyography. It was determined that the majority of patients with peripheral neuropathy were women, above 65 years of age, low body mass index, high body surface area, and smokers. While the serum uric acid level of all patients was 5.1 mg/dl (1.9- 9.1), it was significantly higher in patients with peripheral neuropathy than in those without neuropathy (p = 0.0012). We found that ORPN may develop in patients with SUA levels higher than 5.96 mg/dL in men and 6.04 mg/dL in women at the time of diagnosis, and these cut-off values had a sensitivity of 40% and a specificity of 95.40% in men, respectively, while the sensitivity in women was 84.6% and the specificity was 83.87%. In multivariable analysis, female gender, smoking, high body surface area and high serum uric acid level were determined to be independent predictors for all patients.

Conclusion: Despite the limitations of the study, it was concluded that the possibility of developing oxaliplatin-induced peripheral neuropathy may be high in patients with high serum uric acid levels. This study needs to be repeated prospectively and evaluated in larger cohorts.

Background: Allogeneic hematopoietic cell transplantation (alloHCT) is an established curative treatment for hematologic malignancies and other severe blood disorders. However, alloHCT is also known for its significant side-effects.

Summary: Here we review recent advances in targeted molecular therapy, immunotherapy, infectiology and diagnostics that have enhanced the tolerability and the efficacy of alloHCT, expanding its use to less fit and elderly patients. We analyze developments in conditioning regimens, donor selection and the management of graft versus host disease (GVHD) and infections and discuss post-transplantation strategies to prevent relapse.

Key message: In a fresh perspective alloHCT can serve as a platform to enhance the potential of emerging targeted and immune therapies.

Introduction: Multidisciplinary team (MDT) oncology meetings foster collaboration among healthcare practitioners to determine the most appropriate course of action for cancer patient care. Defining what is "best" for a patient is complex, involving clinical guidelines, patient needs, evidence-based practices, and available treatment options. Patient participation offers unique insights into cultural and psychosocial preferences, shifting away from the paternalistic healthcare model. This study aimed to explore the benefits, barriers, and challenges associated with integrating patient preferences (PPs) into oncology MDT decision making.

Methods: Thirty participants from two major UK oncology centers completed questionnaires, with eight participating in the follow-up interviews.

Results: The key benefits of incorporating PPs included improved patient satisfaction, treatment adherence, and decision-making efficiency. The major barriers were lack of clinical information, insufficient knowledge of preferences, and time constraints. Challenges within MDT meetings include poor attendance of key clinicians, inadequate chairing, and physical constraints.

Conclusion: This is the first UK-based study to explore physicians' perspectives on incorporating PPs into oncology decision-making. While PPs are valued, integration is often hindered by systemic pressure within the NHS. The findings highlight the complex interplay between patient-centered care ideals and practical implementation challenges, suggesting areas for improvement that incorporate patient voices into cancer care decision-making.