Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to overcome tyrosine kinase inhibitor (TKI) resistance in epithelial growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) cells in vivo and in vitro. However, little is known about the putative induction of non-apoptotic cell death pathways by statins. We investigated the effects of pitavastatin and fluvastatin alone or in combination with erlotinib in three NSCLC cell lines and examined the activation of different cell death pathways. We assessed apoptosis via fluorometric caspase assay and poly (ADP-ribose) polymerase 1 (PARP) cleavage. Furthermore, annexinV/propidium iodide (PI) flow cytometry was performed. Small molecule inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD), necrostatin 1 (Nec1), ferrostatin 1 (Fer1), Ac-Lys-Lys-Norleucinal (Calp1) were used to characterise cell death pathway(s) putatively (co-)activated by pitavastatin/erlotinib co-treatment. Synergism was calculated by additivity and isobolographic analyses. Pitavastatin and fluvastatin induced cell death in EGFR TKI resistant NSCLC cells lines A549, Calu6 and H1993 as shown by caspase 3 activation and PARP cleavage. Co-treatment of cells with pitavastatin and the EGFR TKI erlotinib resulted in synergistically enhanced cytotoxicity compared to pitavastatin monotherapy. Flow cytometry indicated the induction of alternative regulated cell death pathways. However, only co-treatment with mevalonic acid (Mev) or the pan-caspase inhibitor zVAD could restore cell viability. The results show that cytotoxicity mediated by statin/erlotinib co-treatment is synergistic and can overcome erlotinib resistance in K-ras mutated NSCLC and relies only on apoptosis.

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.

Purpose: Misconceptions regarding activity and toxicity of therapeutic interventions are common among cancer patients. There is little knowledge about the factors that contribute to a more realistic perception by patients. Methods: This pilot study was designed as a prospective questionnaire survey and included 101 therapy-naïve patients treated at the Division of Oncology, Medical University of Vienna. After obtaining written informed consent, patients’ expectations about treatment aims, side effects and the satisfaction with their oncologic consultation were interrogated before the first treatment cycle by questionnaires. Results: Of 101 patients, 53 (53%) were female and 67/101 (66%) were treated with curative attempt in an adjuvant or neo-adjuvant setting. The most common diagnoses were lung cancer (31%) and breast cancer (30%). Although 92% of patients were satisfied with the information given by their oncologist, palliative patients were more likely to declare that not everything was explained in an intelligible manner (p = 0.01). Patients with a first language other than German stated more often that their physician did not listen carefully enough (p = 0.02). Of 30 patients, 26 (87%) receiving chemotherapy with palliative intent believed that their disease was curable. Concerning adverse events, female patients anticipated more frequently hair loss (p = 0.003) and changes in taste (p = 0.001) compared to men. Patients under curative treatment were more likely to expect weight loss (p = 0.02) and lack of appetite (p = 0.01) compared to patients with palliative treatment intent. Conclusion: In conclusion, cancer patients were satisfied with the patient-doctor communication. This prospective study aggregated patients’ concerns on side effects and the perception of therapeutic goals in therapy-naïve patients. Of note, the majority of patients treated in the palliative setting expected their treatment to cure the disease.

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.

Summary: Salivary gland cancers (SGC) are a rare and heterogeneous group of malignancies. Most frequently tumors arise in the parotid gland. The most common histologic subtypes are adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). Rare subtypes include salivary ductal carcinoma (SDC), mammary analogue secretory carcinoma (MASC) and adenocarcinoma not other specified (AC NOS). For locally advanced or metastatic disease, chemotherapy has been the mainstay of therapy. The course of disease differs markedly between the subtypes, especially ACC usually presents as slowly progressing disease. Due to the rarity of these tumors only small phase I/II studies exist, which report efficacy of cytotoxic regimens in advanced SGC. However, due to advances in the understanding of tumor biology and molecular testing, drugable genetic changes like androgen receptor (AR) status, HER2/neu overexpression and neurotrophic tyrosine receptor kinase (NTRK) gene fusion have evolved as potential therapy targets in subsets of SGC. Consequently therapy with androgen receptor blockade (ARB) can be offered to patients with AR expressing tumors. Anti-HER2 therapy with trastzumab is an option for the treatment of tumors with overexpression of HER2/neu and finally NTRAK inhibitors can be used for tumors harboring a NTRK gene fusion. Taken together, due to the small number of patients, data from large phase III studies for the treatment of SGC are missing. However, promising targeted therapy approaches have been recently undertaken.