Fengerfallesen6989

New cases of the novel coronavirus, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to rise worldwide. A few reports have showed that mortality due to SARS-CoV-2 is higher in elderly patients and other active comorbidities including cancer. To date, no effective treatment has been identified and management for critically ill patients relies on management in intensive care units. Patients with lung cancer are at risk of pulmonary complications from COVID-19. Furthermore, the use of chemotherapy might have a negative impact in patient's outcome. Therefore, the risk/benefit ratio of systemic anticancer treatment (SACT) has to be considered. For each patient, several factors including age and comorbidities, as well as the number of hospital visits for treatment, can influence this risk. Each hospital around the world has issued some internal policy guidelines for oncologists, aiming to limit risks during this difficult time. We hereby propose a tool to support oncologists and physicians in treatment decision for patients with lung cancer. There are several variables to consider, including the extent of the epidemic, the local healthcare structure capacity, the risk of infection to the individual, the status of cancer, patients' comorbidities, age and details of the treatment. Given this heterogeneity, we have based our suggestions bearing in mind some general factors There is not easy, universal solution to oncological care during this crisis and, to complicate matters, the duration of this pandemic is hard to predict. It is important to weigh the impact of each of our decisions in these trying times rather than rely on routine automatisms. © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.The PD-1 ligands PD-L1 and PD-L2 are commonly expressed on the surface of cells, where they regulate immune system activation. However, the specific role played by each ligand has been unclear. Using site-directed mutagenesis, surface plasmon resonance, and crystallography, Philips et al. explore the distinct features of PD-L2 and identify a specific evolutionary event linked to its appearance. This work provides a deeper understanding of how the immune system adapted to mammalian placental gestation and could be an important consideration in the development of new immune checkpoint therapies. © 2020 Dustin and Zenclussen.PURPOSE We performed a first-in-human clinical trial. The aim of this study was to determine safety and feasibility of PET imaging with 18F-PARPi in patients with head and neck cancer. learn more PATIENTS AND METHODS Eleven patients with newly diagnosed or recurrent oral and oropharyngeal cancer were injected with 18F-PARPi (331 ± 42 MBq) and dynamic PET/CT imaging was performed between 0 min and 25 min post-injection. Static PET/CT scans were obtained at 30 min, 60 min and 120 min post injection. Blood samples for tracer concentration and metabolite analysis were collected. Blood pressure, ECG, oxygen levels, clinical chemistry and CBC were obtained before and after tracer administration. RESULTS 18F-PARPi was well-tolerated by all patients without any safety concerns. Of the 11 patients included in the analysis, 18F-PARPi had focal uptake in all primary lesions (n = 10, SUVmax = 2.8 ± 1.2) and all 18F-FDG positive lymph nodes (n = 34). 18F-PARPi uptake was seen in 18F-FDG negative lymph nodes of three patients (n = 6). Focal uptake of tracer in primary and metastatic lesions was corroborated by CT alone or in combination with 18F-FDG. The overall equivalent dose with 18F-PARPi PET was 3.9 mSv - 5.2 mSv, contrast was high (SUVmax(lesion)/SUVmax(trapezius muscle) = 4.5) and less variable than 18F-FDG when compared to the genioglossus muscle (1.3 versus 6.0, p = 0.001). CONCLUSIONS Imaging of head and neck cancer with 18F-PARPi is feasible and safe. 18F-PARPi detects primary and metastatic lesions, and retention in tumors is longer than in healthy tissues. Copyright ©2020, American Association for Cancer Research.PURPOSE Although cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors significantly extend tumor response in patients with metastatic ER-positive (ER+) breast cancer, relapse is almost inevitable. This may in part reflect the failure of CDK4/6 inhibitors to induce apoptotic cell death. We therefore evaluated combination therapy with ABT-199 (venetoclax), a potent and selective BCL2 inhibitor. EXPERIMENTAL DESIGN BCL2 family member expression was assessed following treatment with endocrine therapy and the CDK4/6 inhibitor palbociclib. Functional assays were used to determine the impact of adding ABT-199 to fulvestrant and palbociclib in ER+ breast cancer cell lines, patient derived organoid (PDO) and patient derived xenograft (PDX) models. A syngeneic ER+ mouse mammary tumor model was used to study the effect of combination therapy on the immune system. RESULTS Triple therapy was well-tolerated and produced a superior and more durable tumor response compared to single or doublet therapy. This was associated with marked apoptosis, including of senescent cells, indicative of senolysis. Unexpectedly, ABT-199 resulted in Rb dephosphorylation and reduced G1/S cyclins, most notable at high doses, thereby intensifying the fulvestrant/palbociclib-induced cell cycle arrest. Interestingly, a CRISPR/Cas9 screen suggested that ABT-199 could mitigate loss of Rb (and potentially other mechanisms of acquired resistance) to palbociclib. ABT-199 did not abrogate the favorable immunomodulatory effects of palbociclib in a syngeneic ER+ mammary tumor model and extended tumor response when combined with anti-PD1 therapy. CONCLUSIONS This study illustrates the potential for targeting BCL2 in combination with CDK4/6 inhibitors and supports investigation of combination therapy in ER+ breast cancer. Copyright ©2020, American Association for Cancer Research.Bone metastases are common, especially in more prevalent malignancies such as breast and prostate cancer. They cause significant morbidity and draw on healthcare resources. Molecular and hybrid imaging techniques, including single photon emission computed tomography with computed tomography (SPECT/CT), positron emission tomography / CT and whole-body MRI with diffusion-weighted imaging (WB-MRI), have improved diagnostic accuracy in staging the skeleton compared to previous standard imaging methods, allowing earlier tailored treatment. With the introduction of several effective treatment options, it is now even more important to detect and monitor response in bone metastases accurately. Conventional imaging, including radiographs, CT, MRI and bone scintigraphy, are recognized as being insensitive and non-specific for response monitoring in a clinically relevant time frame. Early reports of molecular and hybrid imaging techniques, as well as WB-MRI, promise earlier and more accurate prediction of response vs non-response but have yet to be adopted routinely in clinical practice.