Oncology Research and Treatment最新文献

Introduction: Brain metastases are a common risk in non-small cell lung cancer (NSCLC) patients. Generally, brain metastases are associated with reduced survival rates, and brain imaging is recommended during tumour staging. Here, we assess the incidence and survival among patients with non-curative advanced NSCLC (aNSCLC) with brain metastases, as well as the use and timing of brain imaging based on German claims data.

Methods: Our study was based on claims data from about 4.5 million patients in Germany who are insured via statutory health insurance. 28,578 lung cancer patients were identified via ICD-10 code C34 during the study period from 2015 to 2021. Among them, patients with aNSCLC were determined using specific ICD-10 codes in combination with NSCLC disease- and stage-specific treatments. Brain metastases were identified via ICD-10 codes, while brain imaging was detected via OPS (operation and procedure classification system) and EBM (German Uniform Assessment Standard) codes.

Results: The study population comprised 8,111 patients with aNSCLC, of which 7,010 patients (86.4%) had metastatic NSCLC (mNSCLC) and 1,101 patients (13.6%) had locally advanced NSCLC not amenable to curative-intended local therapy. The median overall survival (OS) of the entire study population was 9.2 months (95% CI: 8.9-9.6 months), of which 20.4% presented with brain metastases at initial diagnosis. Patients with brain metastases at diagnosis had a median OS of 6.1 months (5.7-6.6 months), as opposed to patients without brain metastases at diagnosis with a median OS of 9.5 months (9.0-9.9 months). Of the whole study population, 5,394 patients (66.5%) had received brain imaging at initial NSCLC diagnosis. Brain imaging was more common among patients with mNSCLC compared to those with locally advanced NSCLC (69.2% vs. 49.5%). The diagnostic setting (inpatient vs. outpatient, rural vs. urban location) had no apparent impact on the usage of brain imaging.

Conclusion: Our study provides valuable insights into the routine practice of brain imaging in NSCLC patients in Germany. Our findings align with published evidence regarding incidence rates and mortality, again emphasising the prognostic relevance of brain metastases. Therefore, brain imaging at diagnosis should be used more commonly to detect brain metastases early on, which appeared insufficiently used in routine practice.

Background: An evidence-based clinical practice guideline for systemic cancer treatment in pregnant women is lacking.

Summary: The German, Austrian, and Swiss Societies for Hematology and Medical Oncology have provided an updated guideline on systemic cancer treatment in pregnancy.

Key messages: The gestational age and a multidisciplinary team are essential for treatment planning. A risk-benefit analysis is mandatory. Ultrasound and magnetic resonance imaging are preferred for diagnostic imaging during pregnancy. In the first trimester, there is an increased risk of malformations and miscarriages following systemic tumor therapy; therefore, such therapy is generally discouraged during this period. Systemic tumor therapy in the second and third trimester can result in outcomes comparable to a normal course of pregnancy and development. In cases of premature delivery, potential risks for the newborn should be considered. Systemically administered tumor therapeutics are dosed according to current standards. The use of certain medications, such as tyrosine kinase inhibitors, VEGF antibodies, anti-hormonal substances, and immune checkpoint inhibitors, is generally advised against during pregnancy. Supportive therapy agents can predominantly be used in the second and third trimesters without significant late effects for the newborn. The goal is a spontaneous delivery as for non-cancer patients; early induction of labor and Caesarian section (except for patients with cervical cancer) are discouraged. A minimum interval of 3 weeks between myelosuppressive systemic therapy and delivery is recommended to reduce potential complications. As a rule, normal early and late child development can be expected if established treatment recommendations are followed. Patient data should be entered into established registries.

Introduction: The COVID-19 pandemic led to restrictions in public life and significantly impaired treatment processes for oncological treatments. In this trial, we compared breast cancer (BC) patients' psychological stress before and after the availability of vaccines against COVID-19.

Methods: Patients that received preoperative, postoperative, or palliative treatment for their BC diagnosis during the COVID-19 pandemic between 2020 and 2022 were included. Cohort 1 comprised patients prior to the availability of vaccines and Cohort 2 comprised patients from 2021 when vaccines against COVID-19 were available. We evaluated differences in mental state, influencing factors on quality of life (QoL) and factors causing distress during their BC treatments by several questionnaires.

Results: When comparing 82 BC patients (Cohort 1) with 91 patients (Cohort 2), we found quite similar psychosocial parameters and secondary diagnoses. Eighty-five patients (93.41%) in Cohort 2 had been vaccinated. The cohorts did not differ regarding their concern toward the pandemic. We found that stress caused by insecurity (19.00 [11.00-26.00] in Cohort 1 vs. 16.00 [10.00-21.00] in Cohort 2 [p = 0.050]) and stress by loss (11.00 [9.00-16.00] in Cohort 1 vs. 10.00 [7.00-13.00] in Cohort 2 [p = 0.047]) decreased in Cohort 2, while all other parameters of distress did not show differences. Patients in Cohort 2 felt moderate burden due to restriction of accompanying persons and visits during hospitalization without corresponding changes to the QoL. In contrast, their own vaccination and the vaccination of their relatives showed positive impact on their QoL. Vaccination appeared to only minimally affect everyday behavior.

Conclusion: This trial shows positive psychological vaccination effects with only a limited influence on the distress of BC patients.

Introduction: Pharmacogenetics (PGx) plays a crucial role in precision medicine by identifying genetic variations that influence drug metabolism. For example, variants in dihydropyrimidine dehydrogenase (DPYD) have an impact on DPD enzyme activity and consequently on the metabolization of 5-fluorouracil, which can lead to severe adverse drug reactions. Therefore, pre-emptive DPYD genotyping was endorsed by the European Medicines Agency (EMA) in mid-2020 and subsequently included in national guidelines. In this study, we evaluated the impact of these guidelines on the request behavior for DPYD genotyping at a German university hospital in Mannheim (UMM) and on participation in external quality assessment (EQA) schemes in the European setting.

Methods: A retrospective analysis was conducted on 386 DPYD genetic tests performed as part of standard care at the University Medical Center Mannheim from 2015 to 2021. Patient data, including demographics, diagnosis, and treatment, were obtained from electronic health records. Additionally, EQA data from the Reference Institute for Bioanalytics from 2015 to 2023 were analyzed to evaluate the adoption of DPYD testing across European laboratories.

Results: The study observed a significant increase in DPYD genotyping requests at UMM following the EMA recommendation in 2020, with an up to 29-fold increase compared to previous years. Furthermore, a shift from post-treatment to pre-treatment genotyping was observed. DPYD variants were detected in 6.5% of cases, with DPYD HapB3 being the most frequent. EQA data from 23,114 genotypes demonstrated a growing participation in proficiency testing across Europe, indicating broader clinical adoption, and confirmed the impact on testing requirements in national guidelines on integration into clinical workflows.

Conclusion: The integration of DPYD testing into national guidelines has significantly increased its clinical adoption, enhancing patient safety in oncology. However, standardization challenges remain. Further harmonization of guidelines and expansion of PGx testing may further optimize chemotherapy safety in the future.

Introduction: Pneumonia is a common and serious complication during high-risk neutropenia in patients with cancer. Even though sex differences were described in patients with infectious diseases or cancer in general, sex-specific analyses for pneumonia are lacking. This exploratory study aimed to compare epidemiology and outcome of pneumonia between men and women in this high-risk cohort.

Methods: Patient data were harmonized from four primary databases collected by our research group at two tertiary care centers in Germany. High-risk neutropenia was either defined by duration of neutropenia or assumed for autologous or allogeneic hematopoietic stem cell transplantation. All patients who developed pneumonia associated with febrile neutropenia were stratified by sex, and their characteristics during the first observed pneumonia case were compared. Additionally, all identified causative pathogens were stratified by sex and described.

Results: In total, 906 patients contributed 1,511 cases of high-risk neutropenia. Pneumonia occurred in 110/689 (16.0%) of cases in women and 132/822 (16.1%) of cases in men. Patient characteristics such as age, underlying disease, and risk factors like duration of neutropenia did not show significant differences. Intensive care unit treatment was needed by 15/97 (15.5%) women and 22/104 (21.2%) men, and the inhospital mortality was 5/98 (5.1%) in women and 12/113 (10.6%) in men, but this result did not reach statistical significance. Seventy-three causative pathogens were identified. Among them, Gram-positive pathogens were identified in three times as often in women (13/36 [36.1%]) than in men (5/37 [13.5%]; p < 0.001, q = 0.002). In contrast, fungi were identified twice as often in men (13/37 [35.1%]) than in women (7/36 [19.4%]; p < 0.001, q = 0.002).

Conclusion: Our exploratory study suggests that while pneumonia rates are similar in women and men, pathogen patterns differ and outcomes may be different. These findings should be verified prospectively and in larger cohorts.

Introduction: The number of patients requiring anticoagulation, e.g., for cardiovascular diseases, is increasing, even in patients with immune thrombocytopenia (ITP). However, detailed guidelines and studies are lacking. In clinical trials in ITP, patients taking anticoagulants are usually excluded and patients with thrombocytopenia are often excluded from anticoagulation studies. Our main goal was to highlight factors that influence anticoagulation decision-making in the clinical routine.

Methods: We conducted a survey to explore the preferred management of anticoagulation therapy in patients with ITP. It presented common patient scenarios and elicited factors influencing decisions regarding whether to initiate anticoagulation therapy.

Results: We surveyed 235 colleagues in Germany, Austria, and Switzerland. A total of 210 respondents specialized in hematology; 13 had advanced training in hemostaseology. About half (110/210; 55%) of participants treat 5-10 patients with ITP per month. The recommended platelet thresholds for antithrombotic therapy were similar among patients with ITP. Most participants recommended a minimum platelet count of 50 × 109/L for anticoagulation therapy in most scenarios. However, there was great variability in individual practice patterns among the respondents. The psychosocial status of patients was important for decision-making.

Conclusion: Deciding on anticoagulation therapy in patients with ITP remains challenging. Our survey illustrated the diverse perspectives of medical professionals on managing anticoagulation therapy in ITP. A platelet count of >50 × 109/L was considered safe. In patients with lower platelet counts, other influencing factors such as bleeding tendency, comorbidities, and psychosocial status become relevant. Our findings emphasize the importance of balanced clinical judgment, the need for evidence-based guidelines, and open discussions with patients to optimize treatment strategies.

Introduction: Gastrointestinal malignancies account for 25% of all cancer cases and 35% of cancer-related mortality. Next-generation sequencing (NGS) can elucidate the genomic landscape of gastrointestinal cancers; tissue-based genotyping has traditionally been used, but liquid biopsy-based genotyping is a noninvasive alternative. Moreover, geographical variations in the genomic landscape of gastrointestinal cancers have not been fully elucidated. This retrospective study aimed to gain insight into the genomic landscape of patients with gastrointestinal cancers from the Asia and Middle East (AME) region using plasma-derived circulating tumor DNA (ctDNA).

Methods: From routine clinical practice, 2,601 plasma samples were collected from 2,062 patients with gastrointestinal cancers in the AME region. NGS profiling was conducted using the Guardant360® assay. The frequency of biomarkers that can aid decision-making in cancer patients was investigated.

Results: Single-nucleotide variants affected most commonly TP53 (70.4%), KRAS (44.0%), APC (25.7%), ATM (15.1%), and PIK3CA (12.3%). Copy number alterations were most often observed in EGFR (13.7%), CCNE1 (5.9%), PIK3CA (5.0%), MYC (4.7%), and FGFR1 (4.6%); fusions were detected in 1.6% of patients and most frequently affected FGFR2, RET, ALK, FGFR3, and NTRK1/3. In patients with pancreatic adenocarcinoma, the most frequently observed clinically informative genomic biomarkers occurred in KRAS (G12C, 1.6%; all others, 67.1%), BRCA1/2 (4.1%), BRAF (V600X, 1.5%), and microsatellite instability-high (MSI-H) (1.0%). In patients with colorectal cancer, the most common clinically relevant alterations were KRAS (49.0%), BRAF (V600E, 7.6%), and NRAS (5.7%) mutations; ERBB2 amplifications (2.5%); and MSI-H (1.8%). In patients with biliary tract cancers, actionable alterations included IDH1 mutations (11.1%), ERBB2 amplifications (4.6%), FGFR2 fusions (2.0%), MSI-H (2.0%), and BRAF V600E (1.5%). In patients with gastric or gastroesophageal junction adenocarcinomas, actionable alterations included ERBB2 amplifications (10.1%) and MSI-H (3.6%).

Conclusion: Our data provide insight into the genomic landscape of patients with gastrointestinal cancers from the AME region using ctDNA analysis. These findings highlight the potential utility of liquid biopsy as a noninvasive tool for characterizing tumor genomic profiles and support its role in clinical practice.

Introduction: Radiotherapy resistance leads to treatment failure and disease progression in patients with cervical cancer. This study aims to elucidate the molecular underpinnings of radiotherapy response in cervical cancer by identifying radiotherapy sensitivity genes (RSGs).

Methods: We utilized two GEO expression profiling datasets (GSE3578 and GSE6213) comprising cervical cancer biopsy samples taken before and during radiotherapy to identify differentially expressed genes (DEGs) using the RankProd meta-analysis approach. Subsequent analysis was conducted using data from the TCGA-CESE project to further determine the RSGs and investigate their associations with survival prognosis, immune cell infiltration, and drug sensitivities. The differential expressions of the candidate RSGs were validated in an independent set of cervical cancer patients by qPCRs.

Results: A total of 518 DEGs were identified, with 305 genes upregulated and 213 genes down-regulated during radiotherapy. Six key RSGs were identified as significantly associated with radiotherapy response. Cox regression analysis revealed that upregulations of IL1RAP and GPR15 were associated with an increased risk of poor survival prognosis. Functional enrichment analysis highlighted the involvement of these genes in critical biological processes such as cytokine signaling and immune regulation. Correlation analyses demonstrated significant associations between RSG expressions and M2 macrophage and γδT cell abundances in tumor microenvironment, as well as drug sensitivities. The expression of IL1RAP was significantly higher in the complete response group, supporting the bioinformatic finding.

Conclusion: Our findings on RSGs could potentially serve as potential biomarkers for predicting radiotherapy response and as therapeutic targets to enhance the efficacy of radiotherapy.

Background: Ovarian cancer is the gynecological cancer with the worst overall survival worldwide. Around 70% of patients are diagnosed in an advanced stage. Since low residual tumor after surgery has been repeatedly observed to deeply affect survival, achieving complete resection of tumor with no macroscopic residual disease through primary debulking surgery (PDS) has become the standard of care in advanced ovarian cancer.

Summary: The concept of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) was introduced in order to improve resectability in patients who otherwise, due to advanced age, poor performance status, or extensive tumor burden, cannot be optimally operated. Patient-related factors like age, performance status, comorbidities, and nutritional status can all affect the survival and are all key factors in the selection process. Accurately assessing tumor extension and therefore allocating a patient to the NACT/IDS strategy is of great importance and can be achieved either through imaging (CT scan, ultrasound, MRI, PET scan) or laparoscopy using different validated laparoscopic scoring systems.

Key messages: There is sizable randomized evidence to support the NACT/IDS as an acceptable strategy in patients with advanced ovarian cancer, in whom a PDS is not possible or would have a suboptimal outcome. Patient- and tumor-related factors play a key role in allocating the right management plan to the right patient.