Christoph Minichsdorfer

Febrile neutropenia (FN) remains a frequent complication of cytotoxic chemotherapy despite G-CSF prophylaxis and is associated with substantial morbidity and mortality. This study characterized FN presentations to the emergency department (ED) and identified patient-, treatment- and microbiological factors associated with patient outcome. This retrospective single-centre real-world cohort study included adult patients (≥18 years) with histologically confirmed malignancies who had received at least one line of systemic therapy and presented to the ED of the Medical University of Vienna with FN between August 2016 and December 2019. Demographic, clinical, microbiological, treatment-related and outcome data were extracted from electronic medical records. Univariable and multivariable logistic regression models were used to identify variables associated with in-hospital and 3-month mortality. Ninety patients with FN were analysed (median age 65 years, range 18-87, 42% female). The most common malignancies were lymphoma (22%), hematologic malignancies (11%) and lung cancer (11%). In-hospital and 3-month mortality rates were 18% and 29%, respectively. Non-survivors more frequently presented with hepatic or pulmonary metastases (both p = 0.009), palliative treatment intent (p < 0.001) and lower rates of therapeutic G-CSF administration (p = 0.013). Elevated CRP on admission was associated with in-hospital mortality (p = 0.007), whereas higher LDH levels were associated with 3-month mortality (p = 0.016). Blood culture positivity was common (33/84; 39%) and associated with higher in-hospital mortality (p = 0.007) and reduced 3-month survival (p = 0.006). In the multivariable analysis, no single factor was significantly associated with in-hospital mortality, whereas elevated LDH (aOR 1.01 per U/L, p = 0.008), positive blood culture (aOR 6.71, p = 0.010) and curative treatment intent (aOR 0.085, p = 0.036) were associated with 3-month mortality. FN remains associated with substantial short-term mortality, particularly in patients with palliative treatment setting, elevated inflammatory markers or positive blood cultures. Therapeutic G-CSF use showed a protective association, whereas higher CRP and LDH levels were associated with adverse outcomes.

Background: Breast cancer (BC) is the most common malignancy in women, and the subtype is a key prognostic factor. In HER2-positive disease, HER2-directed therapies have significantly improved outcomes, though they carry the risk of cardiotoxicity which could cause emergency department (ED) visits.Objectives: To assesses reasons for ED presentations by BC subtype, 3-month mortality (3MM) and cardiologic side effects of HER2-directed therapy.Methods: In this retrospective study, visits of BC patients at an Austrian tertiary care ED were evaluated. Frequency rates of BC subtypes and subtype-specific 3MM rates were calculated using a Chi-Square test (separately for early and advanced BC patients). An association between HER2-directed therapies and cardiologic ED visits was investigated using a Fisher’s exact test and a multinomial logistic regression controlling for age.Results: There was a total of 463 ED visits among 322 patients between August 2016 and December 2019. Subtype distribution was as follows: 42% (n=135) luminal B/HER2-negative, 23% (n=74) triple negative, 16% (n=50) luminal B/HER2-positive, 10% (n=33) luminal A and 9% (n=30) HER2-positive (non-luminal). Subtype was significantly associated with 3MM after ED visits in advanced BC patients (p=0.006), with the highest mortality rate in TNBC (54%). Active HER2-directed therapy (n=70) was associated with increased cardiologic ED visits (OR = 4.536 [95%CI, 1.850-11.125]).Conclusions: BC subtype influenced both the frequency of ED visits and survival. HER2-directed therapy was associated with an increased risk of cardiologic ED visits among real-world cancer patients, indicating the need for tailored cardio-oncology care strategies to optimize tolerability and reduce healthcare burdens.

Purpose: Cancer represents the leading cause of mortality in high-income countries. In the last years, the rate of emergency department (ED) visits by cancer patients has increased 5.5-fold. These ED visits impose a significant economic burden and may indicate the progression of the oncologic disease. The goal of this retrospective study was to identify patient-derived risk factors, especially focusing on serum albumin and body mass index (BMI) for 90-day mortality following unplanned ED visits by cancer patients. Methods: A retrospective chart review of all patients with an ICD-10 diagnosis for cancer undergoing palliative treatment presenting at the ED between 2016 and 2018 at the General Hospital of Vienna was performed. Laboratory values, emergency severity index (ESI), and BMI were collected at the ED presentation. 90-day mortality (90MM) was calculated from the ED presentation. Results: A total of 448 cancer patients were included. Lung cancer (19.2%) and pancreaticobiliary cancer (15.6%) were the most frequent diagnoses. The main reasons for ED visits were pain (20.5%) and fever (17.4%). Sixty-nine percent of patients had to be admitted and 17.5% of patients died during hospitalization. 90MM was highest for patients with low albumin (< 35 g/L vs. > 35 g/L: 60.4% vs. 31.4%; p < .0001). When incorporating albumin levels and BMI, patients with both values below the cutoff had the highest risk for death (HR 4.01, 95% CI 2.30–7.02). Conclusion: Cancer patients face a high risk for hospitalization when presenting at the ED. The 90MM rate is highest in patients with low BMI and albumin levels. This highlights an especially vulnerable cohort of cancer patients for whom supportive care and palliative care have to be optimized.

Summary: Background: Febrile neutropenia (FN) is a relatively common complication of cytotoxic chemotherapy. Prophylaxis with granulocyte colony-stimulating factor (G-CSF) can prevent FN and chemotherapy dose delays and enable the use of the higher dose intensities associated with a survival benefit; however, G‑CSF is not always used optimally. Summary: Five medical oncologists with a special interest in supportive care met to discuss the evidence for prophylaxis with G‑CSF to improve survival in cancer patients, identify reasons why this is not always done, and suggest potential solutions. The dose intensity of chemotherapy is critical for maximizing survival in cancer patients but may be reduced as a result of hematological toxicity, such as FN. Use of G‑CSF has been shown to increase the chances of achieving the planned dose intensity in various cancers, including early-stage breast cancer and non-Hodgkin lymphoma. All physicians treating cancer patients should consider the use of G‑CSF prophylaxis in patients receiving chemotherapy, paying particular attention to patient-related risk factors. Key messages: Strategies to optimize G‑CSF use include educating medical oncologists and pharmacists on the appropriate use of G‑CSF and informing patients about the efficacy of G‑CSF and its potential adverse effects. It is hoped that the evidence and opinions presented will help to encourage appropriate use of G‑CSF to support cancer patients at risk of FN in achieving the best possible outcomes from chemotherapy.

Background: High unmet need of ovarian cancer (OC) suggests the discovery of new targeted therapeutics is crucial to improve patient prognosis. Unlike artificial model systems such as cell lines, primary cancer samples recapitulate the complexity of the original microenvironment consisting of cancer cells as well as stromal and immune cells; this is especially important when evaluating IO targets and signalling pathways. Supported by our previous success predicting therapy for late stage haematological cancer patients in the EXALT-I trial using AI-supported functional single cell quantification of drug action (Kornauth et. al. 2021) we set out to systematically reveal novel targets and pathways in OC using small molecule drugs (SMDs) as tools. Single cell phenotypic screening of OC MPAs (malignant pleural effusion and ascites) was enabled by the quantification of drug effects using an end-to-end scalable deep learning driven image analysis tool chain. This custom state-of-the-art AI software is critical to enable robust primary cell screening given the diversity of cells within each sample. This revealed anaplastic lymphoma kinase (ALK), as well as structurally related targets and pathway associated proteins, as being potential novel targets in a subset of OC patient samples. There is sparse literature evidence for therapeutic utilisation of the ALK pathway in OC, and the diversity of responses indicates a further novel patient selection method. Methods: MPAs from OC patients (n = 20) were collected and the sensitivity of the cancer cells to 85 SMDs was evaluated using high content microscopy. Individual cells were segmented and classified using convolutional neural networks and drug responses were estimated from the resulting cell counts. The integration of these results with whole exome and RNA sequencing guided target and pathway prioritisation. Results: Screening for novel sensitivities using SMDs as tools uncovered inhibitors of ALK and related targets as having strong cancer cell cytotoxic effects, recapitulated in solid tumour biopsies. Transcriptomic profiling revealed pathway correlations to ALK inhibitor sensitivity, however non-annotated polypharmacological effects of each drug cannot yet be excluded. Conclusions: Quantifying SMD sensitivity in a disease relevant model system identified ALK as a promising and overlooked target in OC, providing an upstream and potentially more specific target to the recently suggested MEK, PI3K and STAT3 (Papp et. al. 2018, Izar et al. 2020). While further work to confirm the target is required, this study supports a notion of patient-centric drug development using disease relevant models and deep learning. Our work introduces a novel patient-centric tool to advance understanding of the OC target landscape and provides a resource for the development of novel therapeutic approaches. Citation Format: Irene Gutierrez-Perez, Joost Van Ham, Valentin Aranha, Rin Okumura, Elisabeth Waltenberger, Isabella Alt, Claudia Baumgaertler, Maja Stulic, Edgar Petru, Christoph Minichsdorfer, Lukas Hefler, Judith Lafleur, Nikolaus Krall, Thorsten Füreder, Gregory Ian Vladimer, Robert Sehlke, Bojan Vilagos. Deep learning supported high content analysis of primary patient samples identifies ALK inhibition as a novel mechanism of action in a subset of ovarian cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1893.

Background: We investigated the influence of population‐wide COVID‐19 lockdown measures implemented on 16, March 2020 on routine and emergency care of cancer outpatients at a tertiary care cancer centre in Vienna, Austria.Methods: We compared the number/visits of cancer outpatients receiving oncological therapies at the oncologic day clinic (DC) and admissions at the emergency department (ED) of our institution in time periods before (pre‐lockdown period: 1 January – 15 March 2020) and after (post‐lockdown period: 16 March– 31 May 2020) lockdown implementation with the respective reference periods of 2018 and 2019. Additionally, we analysed Emergency Severity Index (ESI) score of unplanned cancer patient presentations to the ED in the same post‐lockdown time periods. Patient outcome was described as 3‐month mortality rate (3‐MM).Results: In total, 16 703 visits at the DC and 2664 patient visits for the respective time periods were recorded at the ED. No decrease in patient visits was observed at the DC after lockdown implementation (P = .351), whereas a substantial decrease in patient visits at the ED was seen (P < .001). This translates into a 26%‐31% reduction of cancer‐related patient visits per half month after the lockdown at the ED (P < .001 vs. 2018 + 2019). There was no difference in the distribution of ESI scores at ED presentation (P = .805), admission rates or 3‐MM in association with lockdown implementation (P = .086).Conclusion: We demonstrate the feasibility of maintaining antineoplastic therapy administration during the COVID‐19 pandemic. However, our data underline the need for adapted management strategies for emergency presentations of cancer patients.