Therapeutic strategies to overcome EGFR mutations as acquired resistance mechanism in ALK-rearranged non-small-cell lung cancer: Case Reports

IntroductionALK tyrosine kinase inhibitors (ALK TKIs) have improved prognosis in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC). However, drug resistance mechanisms occur inevitably during the course of treatment leading to disease progression. Activation of epidermal growth factor receptor (EGFR) bypass signaling pathway is an uncommon cause of acquired resistance to ALK TKIs.MethodWe present two patients with EML4-ALK rearranged NSCLC, developing an acquired EGFR resistance mutation after receiving multiple lines of ALK TKIs.ResultsWhile preclinical models have showed encouraging data, there is a critical need for clinical studies on treatment strategies to overcome this drug resistance. Three real-life therapeutic approaches were used in this report: i) using brigatinib, an inhibitor targeting both ALK and EGFR tyrosine kinases; ii) combining two ALK TKIs together; and iii) delivering doublet platinum chemotherapy. In case 1, time to treatment failure (TTF) was 9.5 months with brigatinib; in case 2, TTF was 10 months with combined TKIs (osimertinib and brigatinib), whereas TTF with chemotherapy was only 2 months. Tolerability profile TKIs combotherapy was acceptable.ConclusionThese case reports underline the therapeutic complexity of EGFR-acquired resistance mutation in ALK+ NSCLC and offers some leads to solve this real-life clinical challenge

Teaching neuroimages: Burkitt dural lymphoma mimicking a subacute subdural hematoma.

International audienceA 59-year-old woman with no history of trauma presented with severe headaches and right-sided weakness. A CT scan showed a left hemispheric isodense subdural collection thought to be consistent with a subacute subdural hematoma (figure 1A). The patient underwent a single parietal burr hole for evacuation, but the neurosurgeon found subdural fleshy tissue and performed a biopsy. Immediate postoperative MRI showed a homogeneous hypercellular subdural mass (figure 1, B–F).1 Pathology was consistent with Burkitt lymphoma (figure 2). Retrospectively, the homogeneous density of the collection argued against hematoma. In nonemergent situations, an atypical radiologic appearance of a subdural hematoma may suggest the need for further radiologic investigations before surgical evacuation.

Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas

Item does not contain fulltextBACKGROUND: Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs. METHODS: We characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis. RESULTS: Our study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs. CONCLUSION: Novel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings