Journal of Cancer Research and Clinical Oncology最新文献

Purpose: Acral melanoma (AM), a rare and aggressive melanoma subtype with poor prognosis, presents unique challenges in treatment due to its distinct molecular and immune characteristics. This case report describes a patient with AM harboring an AGK-BRAF fusion mutation, aiming to explore potential mechanisms of resistance to current treatment modalities.

Methods: We analyzed tumor tissue samples from the primary and metastatic lesions of the patient using next-generation sequencing (NGS) for genomic profiling and multiplex immunohistochemistry (mIHC) to assess the immune microenvironment. The patient underwent multiple lines of treatment, including immunotherapy, chemotherapy, and targeted therapy, with their clinical outcomes documented and evaluated.

Results: The AGK-BRAF fusion mutation and its reciprocal BRAF-AGK rearrangement were identified in both primary and metastatic tumors. Immune profiling revealed abundant CD8 + T cells, PD-L1 + cells, and CD68 + macrophages localized predominantly in the tumor interstitial region, potentially explaining the poor response to immunotherapy. Despite initial disease stabilization with trametinib and lenvatinib, rapid progression occurred, highlighting tumor heterogeneity and limited efficacy of combined therapies.

Conclusion: This case underscores the need for personalized approaches in treating AM, especially those with rare molecular alterations like AGK-BRAF fusion. Insights from genomic and immune profiling may inform future therapeutic strategies to overcome resistance and improve outcomes in this challenging melanoma subtype.

Background: Hepatocellular carcinoma is frequently unrecognized in its early stage limiting the access to the first therapeutic steps resulting in a low cure rate. Therefore, an early diagnosis is crucial. In this scenario the analysis of lipidome and metabolome emerged as a promising tool for early detection.

Aims: Aim of the study was to characterize metabolomic profiles as novel markers of early hepatocellular carcinoma.

Methods: Serum basal levels of metabolites, isolated from a cohort of 90 patients (n = 30 early stage; n = 30 advanced stage; n = 30 liver cirrhosis) were analysed using a nuclear magnetic resonance spectroscopy platform. To assess the predictive value of nuclear magnetic resonance profiles, we included the magnetic resonance imaging follow up of control patients with liver cirrhosis.

Results: Significant differences were observed in the levels of individual parameters that included total cholesterol, LDL and HDL subclasses, Isoleucine, Valine, Triglycerides, Lactate, Alanine, Albumin, alpha Fetoprotein, Dimethylamine, Glycerol, and total Bilirubin levels in cancer compared to liver cirrhosis (p < 0.05). Furthermore, a significant difference in glycerol levels (p < 0.05) and a decreasing trend in dimethylamine were observed in cirrhotic patients who later developed HCC (16%, n = 5). Retrospective MRI analysis revealed precursor lesions in 3/5 patients, initially not classified as HCC due to their size and hemodynamic features.

Conclusion: Nuclear magnetic resonance based assessment of lipidomic and metabolomic profiles permit the differentiation of cancer from liver cirrhosis. The data obtained suggests a possible role of lipidomic based serum profiles for early detection.

Purpose: Busulfan is an important myeloablative agent in various conditioning regimens prior to hematopoietic stem cell transplantation (HSCT) in pediatric patients. This retrospective study compares three different routes of busulfan administration and their impact on transplantation-related mortality (TRM) and overall survival (OS).

Methods: The study included 250 pediatric patients with malignant and non-malignant diseases who underwent HSCT at the Department of Pediatrics, Jena University Hospital, Jena, Germany. One hundred forty-eight patients received busulfan orally without therapeutic drug monitoring (TDM) (group 1), 62 patients received busulfan intravenously (i.v.) without TDM (group 2) and 40 patients received busulfan i.v. with additional TDM (group 3).

Results: The TRM rate at 5 years after transplantation for all patients was 40.5% for group 1, 25.2% for group 2, and 8.4% for group 3 (p < 0.001). The TRM rate at 5 years after transplantation for patients with malignant diseases only was 40.3% for group 1 compared to 28.4% for group 2 and 15.3% for group 3 (p = 0.051). For patients with non-malignant diseases, group 1 showed a TRM rate of 43.8% compared to 15.4% in group 2 and 4.6% in group 3 (p = 0.009). In addition, the 5-year OS rate for all patients was 39.9% for group 1, 61.2% for group 2, and 83.9% for group 3 (p < 0.001). Regarding the OS of the groups for patients with only malignant or only non-malignant diseases, we obtained similar results with p-values of p = 0.017 and p = 0.007, respectively. The cumulative incidence of hepatic sinusoidal obstruction syndrome (SOS) for patients with malignant diseases and a cumulative AUC > 85.0 mg/L x h was 55.6%, while patients with malignant diseases and a cumulative AUC < 85.0 mg/L x h showed a cumulative incidence of 11.1% (p = 0.038).

Conclusion: In this study, we demonstrate that patients with i.v. administration of busulfan with TDM had a significantly lower rate of TRM and a significantly improved OS compared to patients who received i.v. administration of busulfan without TDM, who, in turn, had a better outcome than patients with oral busulfan administration. Additionally, these data emphasize the clinical relevance of AUC measurements in patients with malignant diseases to prevent hepatic SOS.

Purpose: Receiving treatment in certified oncological centers and obtaining a second medical opinion has been proven to enhance both the quality and cost-effectiveness of care for oncological patients. Interdisciplinary care optimizes the treatment of oncological patients by validating the diagnosis and treatment recommendation, emphasizes translational research, and applies oncological therapies in a more target-oriented manner. This study aims to examine the extent of patient adherence to second medical opinions provided at the Comprehensive Cancer Center Erlangen-Metropolitan Area Nuremberg (CCC Erlangen-EMN) and investigates how specific patient characteristics such as age, gender, and type of cancer diagnosis influence the likelihood of adhering to a second opinion.

Methods: This is a prospective, single-center observational study supported by the local statutory health-insurance body (Allgemeine Ortskrankenkasse, AOK). A total of 584 male and female patients with cancer in the fields of urology, gynecology, gastroenterology, or sarcoma, seeking a second medical opinion were assessed for their adherence to the second opinion. Levels of adherence in patient subgroups were compared using appropriate statistical tests. Correction for multiple testing was not performed, due to the exploratory nature of the study.

Results: Almost 75% of the patients adhered to the second opinion recommendations and an additional 10% partially followed them. Men adhered to the second opinion recommendation slightly more often (79.1%) than women (70.7%; chi-square test, P = 0.01). At 83%, second-opinion adherence was highest among patients who had received an incomplete but guideline-compliant first opinion. If the first opinion was not guideline-compliant, about 67% adhered to the second opinion. Adherence to second opinions was not significantly influenced by whether the initial therapy recommendation adhered to guidelines (Fisher's test, P = 0.16 for all departments, P = 0.27 for the gynecology department). Most patients adhered to the second opinion after primary therapy (92.9%).

Conclusions: More than two-thirds of patients ultimately followed the recommendation provided in the second opinion. The results of this study enhance our understanding of patient adherence to medical advice and treatment regimens. This study demonstrated that the majority of patients adhere to second opinions and highlighted the feasibility of easy access to second opinions from a certified cancer center. Women adhered slightly less to second opinions than men. More detailed and comprehensive therapy recommendations could potentially enhance adherence rates in the future.

Purpose: To investigate the efficacy and safety of radiotherapy combined with targeted therapy and immunotherapy for liver cancer with lymph node metastasis (LNM).

Methods: We analysed patients who received radiotherapy for liver cancer with LNM in our hospital from June 2020 to June 2023. 62 patients were enrolled in this study, who received radiotherapy with a median radiation dose of 60.0 Gy, combined with targeted therapy and/or immunotherapy. The objective response rate (ORR), overall survival (OS), progression free survival (PFS), and adverse events were observed to evaluate treatment efficacy and safety.

Results: With a median follow-up of 18.5 months, the best ORR was 90.3%. The median OS was 26.0 months. The 1-year and 2-year OS rates were 78.93% and 57.37%, respectively. The median PFS was 17.0 months, and the 1-year and 2-year PFS rates were 59.06% and 49.22%, respectively. Multivariate analysis showed that alanine aminotransferase (HR = 2.34, 95% CI 1.07-5.11, P = 0.033), prothrombin time (HR = 4.51, 95% CI 1.76-11.57, P = 0.002), alpha fetal protein (HR = 2.94, 95% CI 1.34-6.45, P = 0.007), and the volume of LNM (HR = 3.05, 95% CI 1.25-7.46, P = 0.014) were independent predictors for OS, while non-regional LNM (HR = 3.19, 95% CI 1.24-8.16, P = 0.016) was an independent predictor for PFS. Toxicity was generally mild and moderate.

Conclusions: Radiotherapy combined with targeted therapy and immunotherapy is an effective treatment option, and expected to become new treatment strategy for liver cancer with LNM.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a gastrointestinal tumor with high morbidity and mortality. Despite advances in diagnostic and therapeutic modalities, the outcome and prognosis of PDAC remain poor. Most patients have locally advanced disease (30%-35%) or distant metastases (50%-55%) at the time of diagnosis. The treatment of unresectable pancreatic ductal adenocarcinoma (UR-PDAC) remains an urgent problem. In this study, we report that a patient with UR-PDAC underwent significant tumor shrinkage after PD-1 inhibitor combination chemotherapy, and obtained R0 (pathologically negative margin) resection and long-term survival.

Case presentation: A 51-year-old woman was diagnosed with pancreatic cancer (stage III). She underwent 3 cycles of preoperative neoadjuvant therapy (NAT) with programmed cell death protein 1 (PD-1) antibody in combination with chemotherapy and the tumor shrank from 4.0 × 3.3 cm to 0.9 cm without significant adverse effects. The patient underwent conversion surgery (CS) and achieved R0 resection, and no tumor cells remained as confirmed by pathology.

Conclusion: PD-1 antibody combination chemotherapy regimens have significant efficacy and do not add additional side effects in UR-PDAC patients, heralding advances in UR-PDAC treatment. We may have a way to give UR-PDAC patients access to curative treatment and long-term survival. This case of UR-PDAC patient with PD-L1-negative and microsatellite stability (MSS) gives us a more comprehensive understanding of the treatment options of immune-combination chemotherapy.

Purpose: Diagnosis with UICC stage IV colorectal cancer often indicates palliative treatment to alleviate symptoms. Data on pain in these patients are still scarce but can help improve symptom management. This study therefore aimed to describe patient-reported pain and quality of life.

Methods: 147 palliatively treated stage IV colorectal cancer patients diagnosed between 2018 and 2023 completed the EORTC QLQ-C30 and QLQ-CR29 before and 12 months after treatment initiation within the EDIUM study. Descriptive results for pain and quality of life were examined and compared to reference values. A logistic regression analysis investigated the relationship between quality of life and pain and 1-year survival.

Results: The mean (SD) for the "overall pain" score was 26 (32) (T0) and 35 (32) (T1) for rectal cancer patients and 34 (33) (T0) and 35 (32) (T1) for colon cancer patients. This is higher than the reference value (24 (30)) and indicates high average pain levels. The "overall quality of life" score showed means below the reference value (61 (23)), indicating poorer quality of life (colon: 51 (25) (T0), 56 (22) (T1); rectum: 52 (24) (T0), 51 (22) (T1)). Higher pain levels persisted at both time points, with no patients reporting absence of pain. The logistic regression results suggest a small relationship between pain and quality of life and 1-year survival.

Discussion: This study reveals high levels of pain among palliatively treated colorectal cancer patients, impacting their quality of life. Effective pain management and close monitoring are necessary to improve the quality of life for these patients.

Trail number: DRKS00008724.

Purpose: To explore the development and validation of automated machine learning (AutoML) models for ¹⁸F-FDG PET imaging-based radiomics signatures to predict treatment response in elderly patients with diffuse large B-cell lymphoma (DLBCL).

Methods: A retrospective analysis was conducted on 175 elderly (≥ 60 years) DLBCL patients diagnosed between March 2015 and March 2023 at two medical centers, with a total of 1010 lesions. The baseline PET imaging-based radiomics features of the training cohort were processed using AutoML model AutoGluon to generate a radiomics score (radscore) and predict treatment response at the lesion and patient levels. Furthermore, a multivariable logistic analysis was used to design and evaluate a multivariable model in the training and validation cohorts.

Results: ROC curve analysis showed that the radscore generated by AutoML exhibited higher accuracy in predicting treatment response at the lesion level compared to metabolic parameters (SUVmax, MTV, and TLG) in both the training group (AUC: 0.791, 0.542, 0.667, 0.651, respectively) and the validation group (AUC: 0.712, 0.616, 0.639, 0.657, respectively). Multivariable logistic analysis indicated that NCCN-IPI (OR = 5.427, 95% CI: 1.163-25.317), BCL-2 (OR = 3.714, 95% CI: 1.406-9.816), TMTV (OR = 4.324, 95% CI: 1.095-17.067), and avg-radscore (OR = 3.176, 95% CI: 1.313-7. 686) were independent predictors of treatment response. The multivariable model comprising NCCN-IPI, BCL-2, TMTV, and avg-radscore outperformed conventional models and clinical-pathological models in predicting treatment response. (P<0.05).

Conclusion: The radscore generated by AutoML can predict the treatment response of elderly DLBCL patients, potentially aiding in clinical decision-making.

Objectives: Lung cancer is a leading cause of global cancer mortality. Clinical observations reveal that histological transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is accompanied by mutations in TP53 and RB1. By applying gradually increasing cisplatin concentrations to mimic the escalating drug pressure within the tumor microenvironment, this study investigated the link between phenotypic transformation to SCLC in cisplatin-resistant human lung adenocarcinoma cells and alterations in cellular energy production pathways.

Materials and methods: We established two cisplatin-resistant NSCLC cell lines with varying resistance levels. RNAseq analyses identified TP53 and RB1 gene mutations. Comprehensive functional assays were performed to characterize A549/DDP1 μg/mL and A549/DDP3 μg/mL cells, focusing on proliferation and migratory capabilities. Cellular bioenergetics were assessed through glycolysis and oxidative phosphorylation analyses. Western blotting was employed to examine epithelial-mesenchymal transition (EMT), glucose metabolism, and lipid metabolism markers. Cell cycle distribution was analyzed by flow cytometry. Additionally, a xenograft mouse model was developed for in vivo validation.

Results: TP53 and RB1 mutations were associated with cisplatin concentration-dependent phenotypic transformation, with A549/DDP cells acquiring a more aggressive SCLC-like phenotype (In the article we call the A549/DDPSCLC cells). Analysis of cell bioenergetics profiling and Western blot analyses revealed enhanced glucose metabolism in A549/DDP1 μg/mL cells, while A549/DDPSCLC cells exhibited predominant lipid metabolism. Compound3K and Etomoxir specifically inhibit the activity of PKM2 and CPT1A, respectively, with Etomoxir demonstrating substantially inhibited A549/DDPSCLC cells growth and more cell cycle arrest in the G0/G1 phase. Combinatorial of Compound3K and Etomoxir effectively induced cell death in A549/DDPSCLC phenotype cells in vitro. Etomoxir alone or combined with Compound3K significantly inhibited tumor growth in vivo, with enhanced efficacy in the combination group.

Conclusions: This study provides the first evidence of cisplatin concentration-dependent metabolic reprogramming during NSCLC-to-SCLC transformation. We identified a phenotypic transition from NSCLC to SCLC accompanied by a metabolic shift from glucose to fatty acid metabolism, offering new insights into therapeutic strategies for treatmentresistant lung cancer.