Oncology Research and Treatment最新文献

Introduction: Specialist palliative care (SPC) is rarely integrated into the management of patients with an allogeneic hematopoietic stem-cell transplantation, despite considerable symptom burden and mortality. We aimed to assess hematologists' and nurses' views on SPC integration.

Methods: Multi-center cross-sectional survey with exploratory character. We asked when to best integrate SPC, with three vignettes of patients with good (90% chance of cure/10% risk of death), "fifty-fifty," or poor (10%/90%) prognosis, and assessed preferences regarding integration models and support. We calculated descriptive statistics and associations with chi2/Fisher's exact tests and non-parametric tests.

Results: There were 80 respondents (56% females; mean age: 36.2 years, SD = 7.7; 47 physicians and 33 nurses; 42 in transplant setting, 28 in general oncology/hematology, 9 in intensive care unit, 1 unknown; mean experience: 6 years, SD = 0-25). Participants, regardless of profession, highly agreed to integrate SPC for patients with poor prognosis (Yes = 96%), but a majority would not do so for good prognosis patients (No = 63%). In "fifty-fifty" prognosis, there was no agreement among physicians, whereas nurses would mostly integrate SPC. The preferred integration model for patients with poor or "fifty-fifty" prognosis was a co-management for specific patients' needs. Participants primarily wanted palliative care specialists to support them in addressing life threat with patients.

Conclusion: This study highlights the need to develop accurate integration criteria of SPC in the transplant trajectory, taking multi-professional perspectives into account.

Introduction: Maintenance of subjective well-being and health-related quality of life (HRQoL) play a crucial role in the treatment of metastatic cancer. The metronomic chemotherapy (MCT) may be a favorable treatment option in metastatic breast cancer (MBC) and platinum-resistant recurrent ovarian cancer (ROC). The aim of this study was to evaluate the HRQoL of MBC and ROC patients treated with MCT.

Methods: PROmetronomic was a prospective, monocentric study evaluating the HRQoL in MBC and ROC patients treated with oral cyclophosphamide 50 mg daily (+ oral methotrexate 2.5 mg every other day for MBC) from August 2020 to August 2022. The data were obtained using EORTC QLQ-C30, BR23, OV28, and HADS-D via the eHealth-based platform CANKADO. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

Results: A total of 5 MBC patients and 9 ROC patients were evaluated. The mean global health status was 47.2 at baseline and 36.1 at the end of MCT (p = 0.350). Functional scales and symptoms remained stable during MCT except for the significant increase of fatigue (51.9 vs. 77.8, p = 0.038). Anxiety and depression were without significant alteration (9.1 and 8.1 at baseline vs. 9.3 and 8.1 after MCT). The median PFS and OS were 10.0 weeks and 28.0 weeks, respectively. No ≥grade 3 toxicities were reported.

Conclusion: MCT had no significant impact on HRQoL of our small cohort of heavily pretreated MBC and ROC patients and may represent a valuable treatment option for maintaining HRQoL in selected patients.

Background: With 1:280 carriers, Lynch syndrome (LS) is the most prevalent tumor predisposition syndrome and the most important cause for hereditary colorectal cancer (CRC). Tumors from affected individuals usually present with a deficient expression of mismatch repair (MMR) proteins leading to a high microsatellite instability (MSI).

Summary: With the update of the German S3 guideline CRC, universal MSI/MMR testing is going to be implemented, thus leading to a fundamental change in detection of patients belonging to the risk group of LS. From now on, there is a strong recommendation for performing MMR/MSI diagnostics for every CRC patient regardless of tumor stage not only in the surgical specimen but in the initial tumor biopsy. The subsequent algorithm for germline mutational testing is simplified. For CRC patients under the age of 50 years, multigene panel testing is recommended regardless of MSI/MMR status. Therapeutic considerations leading to MMR/MSI testing in other entities should warrant the same diagnostic approach. Surveillance measures are individualized, especially regarding upper and lower GI endoscopy considering mutational status.

Key messages: Universal MMR/MSI testing is recommended for any CRC patient in the tumor biopsy. Subsequent germline mutational testing should be performed automatically in case of suspicious findings. The detection rate of LS carriers thus will be improved compared to current clinical criteria.

Background: Ovarian cancer (OC) accounts for the most cancer deaths in women worldwide, despite it being the 8th most common one. Almost two-thirds or OC cases present in advanced stages (III/IV) and will require maintenance therapy lasting for up to 36 months in some patients. Despite the introduction of innovative treatments, OC recurs in about 80% of cases in advanced stage disease. Management of recurrent OC is based on multiple factors and includes either surgery, in suitable candidates, followed by chemotherapy or systemic treatment alone. Due to its heavy physical, psychological and economic burden, reducing mortality of OC through prevention and early diagnosis is of utmost importance.

Summary: Prolonged maintenance treatment period in advanced OC led to a more complex follow-up care, which will start during active treatment and hence include management of therapy side effects. Intensifying follow-up through routine measurements of serum CA-125 and the consequent early induction of treatment in asymptomatic relapsed patients failed to improve overall survival compared to symptom oriented follow-up. In recurrent OC patients with a long treatment-free interval, good performance status, low ascitic fluid volume and completely operable tumor in the first diagnosis were found to benefit form a secondary cytoreductive surgery. Several drug classes were heavily tested in recurrent OC, antibody-drug conjugates (ADCs) have been showing some promising results in platinum-resistant recurrent OC. Studies investigating Immunotherapy on the other hand have been much less encouraging. Despite achieving a stage shift toward early stage detection in some trials, large, well-designed studies have so far failed to develop an effective OC screening program that reduces mortality.

Key messages: Managing long-term treatment side effects has become an indispensable part of follow-up care in OC. Symptom oriented follow-up with tumor marker measurement and imaging reserved for symptomatic patients is the standard of care. Allocating the right therapy plan in patients with recurrent OC, to secondary cytoreductive surgery versus systemic treatment will significantly impact progression-free (PFS) and OS. To date, there is no effective screening program for prevention and early detection of OC.

Introduction: This study aimed to investigate the predictive effect of peripheral blood inflammatory indexes on total pathologic complete response (tpCR) in patients with breast cancer receiving neoadjuvant systemic therapy (NST).

Methods: We identified significant prognostic factors for tpCR in the training cohort using univariate and multivariate logistic analysis to build a nomogram based on multicenter data. The performance of the model underwent 1,000-bootstrap resample internal validation and external validation. The area under the receiver operating characteristic (AUC) curve and the calibration curve were used to measure predictive accuracy and discriminative ability. This study was conducted under the Declaration of Helsinki and the approval and supervision of the Ethics Review Committee (2020-SR-053) retrospectively registered.

Results: This retrospective study included 353 patients with breast cancer receiving NST, including 244 and 109 patients in the training and the external validation cohort. Multivariate logistic regression analysis revealed ER status, PR status, HER2 status, T stage, baseline lymphocyte, and percentage change in neutrophil-to-lymphocyte ratio (NLR, an immune system status-associated indicator) as independent predictors of tpCR. Baseline NLR in the tpCR group was significantly lower than that in the non-tpCR group, but percentage change in the NLR was significantly higher in the tpCR group, exhibiting opposite predictive trends. A nomogram was developed based on these results. The AUC curve of the training cohort, bootstrap resampling internal validation, and external validation cohort were 0.832, 0.806, and 0.814, respectively. The calibration curve for the probability of tpCR revealed optimal agreement between the probability and the actual probability. The subgroup analysis revealed that baseline NLR was significantly correlated with tpCR in patients with HER2 overexpression and luminal breast cancer.

Conclusion: A nomogram based on the dynamic change in the NLR was developed, thereby helping adjusting treatment plans because NST may change the functional phenotype of some inflammatory cells and affect tumor microenvironment.

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.