Sarcomatoid carcinoma is a subtype of non-small cell lung cancer (NSCLC) characterized by mesenchymal – epithelial transition component and awful prognosis. In this report, based on a case of stage IV lung sarcomatoid carcinoma with an extraordinary evolution and survival over 4 years, we address unresolved questions about the treatment of this cancer. We also make a literature review about the key factors that characterize this histology and that should be considered when treating those patients. Sarcomatoid carcinoma presents with mutations as KRAS, EGFR, ALK or MET in up to 70% of cases, and an important expression of PD-L1 (also called B7-H1), which can influence treatment of those patients with new drugs as immune checkpoint inhibitors. Immunotherapy has changed the horizon of patients with stage IV lung cancers without driver mutations, as their survival has improved extraordinary. Moreover, radical treatments are being considered in long survivors with oligometastatic disease. In this report, we review targeted and radical therapy, treatment duration and the mechanisms responsible of disease evolution of sarcomatoid tumors.
Methods: Patients treated with an immune checkpoint inhibitor at the Medical University of Vienna from 2015-2018 have been identified using the in-house pharmacy records (n¼580; most frequent entities: 35.6% melanoma, 29.3% lungcancer; 89% stage-IV-disease). A retrospective chart-review was performed to screen for VTE and/or ATE. Cumulative incidences and between-group differences were analysed within a competing-risk framework. Multi-state modelling was applied to study the impact of VTE/ATE on clinical outcomes (mortality & progression of disease).Results: Over a median follow-up of 8.0 months, 39 VTE and 7 ATE were observed. Cumulative incidences of VTE and ATE were 12.9% [95%CI: 7.7-19.5)] and 1.9% [0.7-4.0]. Occurrence of VTE was associated with increased mortality (transition hazardratio (THR): 3.16 [95%CI: 2.06-4.86]) and an increase in risk of early disease progression (THR: 3.51 [95%CI: 2.25-5.48]). Disease-stage (all VTE occurred in stage IV tumors) and history of ) predicted VTE occurrence. No association of VTE with ECOG performance-status, Charlson-Comorbidity-Index or the Khorana-score was observed, and rates of VTE were comparable among subgroups of tumour types and checkpoint-inhibitory agents.Conclusions: Patients with cancer under immune checkpoint inhibitor therapy are at high risk of thromboembolism, especially VTE. Clinical predictors of VTE were advanced disease and history of VTE. Furthermore, VTE occurrence under immunotherapy was associated with increased risk of mortality and disease progression.Legal entity responsible for the study: The authors.
Background: The implementation of liquid biopsy for biomarker testing and response to treatment monitoring in cancer patients would presumable increase laboratory throughput, requiring the development of automated methods for circulating free DNA (cfDNA) isolation. Kit using 57 plasma samples from cancer patients. cfDNA concentration was measured using the Qubit fluorometer. DNA fragments lengt were assessed using the Agilent 2100 Bioanalyzer. Circulating tumor DNA (ctDNA) was quantified by digital PCR (dPCR).Results: Firstly, we observed that MPC method significantly extracted less cfDNA than MR (P<0.0001).However, there were no significant differences in extraction yields of QCNA and MR kits. cfDNA isolation yield was also associated with tumor stage but not with tumor location. Secondly, an oligonucleosomal DNA ladder pattern was observed in 88% of the samples and significant differences in the recovery of mono-, diand tri-nucleosomes DNA fragments were observed between MPC and MR methodologies. Finally, tumor mutation quantification on cfDNA was performed on 38 paired samples using digital PCR. Mutant allele fractions (MAFs) between paired samples were not significantly different.Conclusions: Methods for isolation of cfDNA can affect DNA yield and molecular weight fractions recovery. These observations should be taken into account for cfDNA analysis in routine clinical practice.
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