Oncology Research and Treatment最新文献

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 multigene 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; 8 of these patients received olaparib. In 41.4% of patients, homologous recombination repair 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 were present 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 family history, and KRAS WT patients should be of particular interest.

Introduction: Significant progress has been made in the targeted therapy of metastatic breast cancer (mBC) in recent years. In this context, new biomarkers enable personalized therapy management and individualized therapy monitoring. Therefore, the systemic treatment is based increasingly on the biological characteristics of the tumor disease. Given the challenges of obtaining fresh tumor tissue through biopsies, the significance of liquid biopsies for assessing circulating tumor cells (CTCs) or circulating tumor DNA is of growing importance for the detection of prognostic and predictive biomarkers. Multiple studies have shown that the number of CTCs decreases under therapy, especially under anti-HER2-targeted therapy, and that the expression of the HER2 status on CTCs could play a role in predicting therapy response and therapeutic monitoring. The aim of this study was to analyze the HER2 status of CTCs in mBC patients before and after 3 months of systemic therapy to evaluate changes in the number of HER2-positive CTCs. The study focuses on HER2-low, which plays an increasingly important role in clinical practice due to new developments of HER2 targeting antibody-drug conjugates. In this context, temporal and spatial heterogeneity of the disease represent a major diagnostic challenge.

Methods: A total of 324 patients with complete immunohistochemistry of biopsied metastases were divided into five groups: HER2 negative (-)/hormone receptor (HR) negative (-), HER2 -/HR positive (+), HER2 +/HR±, HER2-low/HR+, and HER2-low/HR-. Before and after 3 months of a new therapeutic line for mBC, CTCs were enumerated and analyzed for HER2 expression using the CellSearch® system. Overall survival of all subgroups was calculated.

Results: The analyses revealed a discrepancy between the HER2 status of CTCs and corresponding tumor tissues in 98 patients (30.2%). The number of CTCs in general and the number of HER2+ CTCs decreased during systemic treatment, mainly in HER2+ tumors, but also in the other subgroups.

Conclusions: Discrepancy in the HER2 status of the metastases and of CTCs was observed in approximately one-third of patients. Measuring HER2 on CTCs could potentially offer a means to longitudinally monitor HER2 status during therapy and simultaneously address challenges such as tumor heterogeneity. Therefore, the predictive value of HER2 on CTCs should be further investigated in clinical trials.

Introduction: The study evaluates the performance of large language model versions of ChatGPT - ChatGPT-3.5, ChatGPT-4, and ChatGPT-Omni - in addressing inquiries related to the diagnosis and treatment of gynecological cancers, including ovarian, endometrial, and cervical cancers.

Methods: A total of 804 questions were equally distributed across four categories: true/false, multiple-choice, open-ended, and case-scenario, with each question type representing varying levels of complexity. Performance was assessed using a six-point Likert scale, focusing on accuracy, completeness, and alignment with established clinical guidelines.

Results: For true/false queries, ChatGPT-Omni achieved accuracy rates of 100% for easy, 98% for medium, and 97% for complicated questions, higher than ChatGPT-4 (94%, 90%, 85%) and ChatGPT-3.5 (90%, 85%, 80%) (p = 0.041, 0.023, 0.014, respectively). In multiple-choice, ChatGPT-Omni maintained superior accuracy with 100% for easy, 98% for medium, and 93% for complicated queries, compared to ChatGPT-4 (92%, 88%, 80%) and ChatGPT-3.5 (85%, 80%, 70%) (p = 0.035, 0.028, 0.011). For open-ended questions, ChatGPT-Omni had mean Likert scores of 5.8 for easy, 5.5 for medium, and 5.2 for complex levels, outperforming ChatGPT-4 (5.4, 5.0, 4.5) and ChatGPT-3.5 (5.0, 4.5, 4.0) (p = 0.037, 0.026, 0.015). Similar trends were observed in case-scenario questions, where ChatGPT-Omni achieved scores of 5.6, 5.3, and 4.9 for easy, medium, and hard levels, respectively (p = 0.017, 0.008, 0.012).

Conclusions: ChatGPT-Omni exhibited superior performance in responding to clinical queries related to gynecological cancers, underscoring its potential utility as a decision support tool and an educational resource in clinical practice.

Introduction: We aimed to evaluate the relationship between positron emission tomography (PET)/computed tomography (CT) parameters with pathological complete response (pCR) in patients with HER-2-positive breast cancer who received neoadjuvant treatment (NACT).

Methods: This retrospective study included 97 patients. The primary endpoint was pCR. ROC analysis was used to find the cut-off values of PET/CT parameters.

Results: The median age of the patients was 50.8 (24.8-77.6) years. When the factors affecting the pCR of the patients after neoadjuvant treatment were analysed, it was observed that patients with low N stage (p = 0.046), patients with high lymph node (LN) metabolic tumour volume (MTV) value (p = 0.030) and high LN total lesion glycolysis (TLG) value (p = 0.014) had more pCR in their operation pathologies after NACT. Binary logistic regression analysis showed that both low N stage (hazard ratio [HR]: 0.073, 95% confidence interval [CI]: 0.016-0.332, p = 0.001) and high LN-TLG value (HR: 0.106, 95% CI: 0.016-0.727, p = 0.022) were independent risk factors affecting pCR. LN-MTV value was not statistically significant in regression analysis (p = 0.456).

Conclusion: As a result of this retrospective study, it was observed that the group with high LN-TLG, one of the PET/CT parameters, had more pCR.

Introduction: Intrahepatic cholangiocarcinoma has demonstrated a consistently increasing incidence in recent years. In cases of unresectability, palliative chemotherapy often remains the only option, typically associated with a poor prognosis. Liver transplantation might be an option for otherwise unresectable intrahepatic cholangiocarcinoma. We aimed to conduct a prospective, non-randomized study to further explore the effects of living donor liver transplantation in the treatment of unresectable neoadjuvant-treated intrahepatic cholangiocarcinoma.

Methods: Patients with unresectable intrahepatic cholangiocarcinoma having a stable disease or tumor regression after systemic chemotherapy without an extrahepatic tumor burden are suitable for study inclusion. For a local control of the tumor, an additional local ablative therapy in means of a selective internal radiotherapy is mandatory. The main concept of the surgical procedure is a liver transplantation using the left (segments II-IV) or the right lobe (segments V-VIII) of a living donor. In oncosurgical optimal conditions, a two-staged hepatectomy combined with the (initially) auxiliary transplantation of a left lateral lobe of a living donor is the possible. The patient recruitment will start in September 2024.

Conclusion: The design of the LIVINCA study may provide patients with otherwise unresectable intrahepatic cholangiocarcinoma a chance for a curative treatment option. This procedure does not reduce the deceased donor organ supply because living donation is the primary treatment option in these patients.

Introduction: Approximately 50% of cancer patients use practices of complementary and alternative medicine (CAM). However, some of these methods may interact with oncological medication. Despite the generally increasing use of CAM in recent years, its prevalence has been studied insufficiently among cancer patients in Germany. Thus, this study aimed to assess the recent use of CAM among cancer patients, evaluate communication on CAM between patients and healthcare providers, and present an overview of the most frequently used practices.

Methods: A cross-sectional study was conducted using a standardized questionnaire including 19 CAM methods as well as sociodemographic and clinical parameters. Also, aspects of communication and quality of life were assessed. Patients were surveyed between September 2022 and June 2023, involving various entities such as breast cancer, lymphoma, and gastrointestinal malignancies. Data analysis was conducted using the Kruskal-Wallis test and one-factor ANOVA.

Results: In total, 154 patients (65.5% female) were included. 88.3% of patients reported use of CAM practices either before receiving their oncological diagnosis or after or both. Out of all patients, 62.3% of patients stated to have begun using at least one CAM practice post-diagnosis. 36.6% of all patients reported to have received information on potential drug interactions by their attending physician, while 60.8% informed their physician about their use of CAM. The most frequently used CAM methods were dietary supplements, massage therapy, and yoga. Overall, female patients reported use of CAM significantly more often than males.

Conclusion: Use of CAM methods appears to be common in this sample of cancer patients. To mitigate risks associated with potential drug interactions, enhanced communication and education between patients and healthcare providers is essential. Integrating a standardized questionnaire on CAM methods into routine oncological care may improve patient safety and treatment outcomes.

Introduction: Screening for anal cancer can help in its secondary prevention. We examined follow-up time for anal cancer screening among high-risk women living with HIV (WLHIV) and whether it varies with the number of risk factors for developing anal cancer.

Methods: A retrospective cohort study involving high-risk WLHIV under 65 enrolled in Medicaid for at least 2 years across 16 US states plus D.C. from 2009 to 2012. High risk was defined by a history of abnormal cervical test results or genital warts. Initial anal cancer screening was the first screening after a high-risk diagnosis, with results classified as normal or abnormal. Follow-up was until the next screening. Follow-up time was analyzed using the Kaplan-Meier estimator and the Cox Proportional Hazards model.

Results: Our cohort included 4,340 high-risk WLHIV, mean (±SD) age 41.8 (±10.2) years. About 18% (763/4,340) had both risk factors, while 9% (374/4,340) had abnormal results on their initial anal cancer screening. The median time, or the time at which 50% of the cohort received follow-up screening, was 17.53 (95% CI = 16.13, 18.30) months overall. Follow-up screening was more common in women with both risk factors for developing anal cancer compared to those with one risk factor (median time: 10.13 [95% CI = 8.90, 11.47] vs. 19.56 [95% CI = 18.36, 21.40] months; adjusted hazard ratio [aHR] = 1.53 [95% CI = 1.38, 1.68]). The follow-up was also more common in women with abnormal results on the initial screening compared to those with a normal result (median time: 7.00 [95% CI = 5.40, 9.23] vs. 18.91 [95% CI = 17.92, 20.12] months; aHR = 2.00 [95% CI = 1.76, 2.28]).

Conclusion: Follow-up time for anal cancer screening in high-risk WLHIV was about 1.5 years but varied according to the risk of developing anal cancer. Future research should examine the guideline-concordance of follow-up screening time given the recently issued guidelines for anal cancer screening.

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 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.

Key messages: ctDNA detection predicts clinical breast cancer recurrence with high sensitivity and specificity. The interval between ctDNA detection and clinical recurrence is defined as lead time and represents a stage of molecular residual disease (MRD). ctDNA-based surveillance and adjuvant therapies have the potential to improve patient outcomes and are currently being evaluated in clinical trials.

Introduction: Artificial intelligence (AI) models offer potential benefits in supporting clinical decision-making, diagnosis, and treatment. The study aimed to compare the performance of ChatGPT-4o (Omni) and Gemini Pro in answering clinical questions and case scenarios related to gynecological oncology and to assess the consistency of their long-term responses.

Methods: A two-phase comparative analysis was conducted. 700 clinical questions (350 per model) were developed and categorized into open-ended and case-scenario questions. Three months later, the same set of questions was presented again to evaluate any changes in performance for accuracy, completeness, and guideline adherence.

Results: Omni outperformed Gemini Pro across all question types (p = 0.001). Omni achieved a mean score of 5.9 for the basic open-ended questions, higher than Gemini, which had 5.1 (p = 0.001). It also maintained a clear advantage in complex, open-ended questions, scoring a mean of 5.6 than Gemini AI's 4.2 (p = 0.001). Omni scored a mean of 5.7 for basic case scenarios, while Gemini AI lagged with a mean score of 5 (p = 0.001). Omni showed a modest improvement in complex, open-ended queries, with an increase of 0.2 points (+3.57%) (p = 0.001). Omni provided more accurate and comprehensive responses in guideline adherence than Gemini, particularly in complex cases requiring nuanced judgment and adherence to oncology protocols. Its responses aligned with the latest guidelines, including the American Society of Clinical Oncology and the National Comprehensive Cancer Network.

Conclusion: Omni is a more reliable and consistent model for answering questions related to gynecological cancers than Gemini. The stability of Omni's performance over time highlights its potential as an effective tool for clinical applications requiring high accuracy and consistency.