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Background: Mesenchymal epithelial transition receptor (MET) alterations, including MET exon 14 skipping mutation, are oncogenic in non-small cell lung cancer (NSCLC) and may confer sensitivity to targeted therapy. Given the rarity and the diversity of exon 14 skipping mutations, diagnosis may be challenging on small-biopsy specimens. Methods: Between March 2014 and May 2018, tissue samples from patients with metastatic NSCLC were analysed for MET exon 14 skipping mutation as part of routine practice in the Pathology Department of the Hospices Civils de Lyon, France. Over the study period, Sanger sequencing and/or two different DNAbased next generation sequencing (NGS) assays were used. Results: Genomic alterations of MET exon 14 were detected in 2.6% (62/2,369) samples of NSCLC analysed for MET exon 14 mutations. Patients were mainly women (38/62, 61%) without smoking history (22/39, 56%) and the median age was 75 years. MET exon 14 skipping mutations were diagnosed by NGS in 50 cases and by classical Sanger sequencing in 12 cases. The frequency of MET mutations was 15.4% when Sanger sequencing was performed at the request of the clinician and 4.1% when the DNA-based NGS assay coverage included the 3' and 5' parts of the MET exon 14 and performed systematically. Conclusions: The frequency of genomic alterations is highly dependent on patient selection and the technical approach.

6003 Background: For pts with R/M SCCHN, new standard of care (SoC) has been recently established with pembrolizumab either alone or combined with platin-5FU (KN 048 – median Overall Survival (OS): 13 months when combined). For pts who need chemotherapy, platinum-5FU-pembrolizumab as first-line treatment appears associated with substantial toxicity that precludes its use in fragile patients. In this context, we investigated the efficacy and tolerance of PDL-1 inhibition with durvalumab combined with weekly carboplatin-paclitaxel as first-line treatment in frail R/M SCCHN pts. Methods: This single-arm phase II study enrolled pts in first-line of their R/M SCCHN and not eligible to standard cisplatin-based CT with an ECOG PS of 0 or 1. Pts received 4 cycles of CT (carboplatin AUC2; paclitaxel 80mg/m² both at D1, D8, D15) and durvalumab (D) 1500mg repeated every 4 weeks for a maximum of 12 months. The primary endpoint was OS Rate at 12 months (m). The study used a Fleming A’Hern design (inefficacy boundary: 47% and target efficacy: 65%), requiring 38 successes among 64 pts. Secondary endpoints were Progression-Free Survival (PFS), Time to Treatment Failure (TTF), objective response rate (ORR) and tolerance. Results: 64 pts (median age 69.5y; 90.6% males, 62.5% PS1) were included, regardless of their PDL-L1 status. Primary tumors were mainly located in oropharynx (37.5%) and larynx (28.1%) with 37.3% PD-L1 CPS≥20. 54.9% were metastatic. The efficacy rule for OS was met with 40 pts (62.5%, unilateral 95%CI: [51.5% - ]) alive at 12m. With a median follow-up of 27.1 m, median OS was 18.0 m (95% CI [11.9-NR]) and the 24m-OS rate was 45% [32%-57%]. Median PFS was 7.0 m (95% CI [5.4-9.9]) and median TTF was 6.0 m (95% CI [4.7-9]). 44/62 pts (71%) achieved an OR (11.3% complete response and 59.7% partial response). Median duration of response was 5.9 m (95% CI [3.4-9.6]). 20.3% of pts experienced G≥3 adverse events related to D, Toxicity led to permanent discontinuation of D in 3.1% of pts. No D-related death was reported. Conclusions: This study performed in fragile patients not amenable to cisplatin-based CT met its primary endpoint on OS and showed a 18 months median OS rate. This combination of durvalumab with weekly carboplatin/paclitaxel was associated with a favorable toxicity profile. Clinical trial information: NCT0372967 .

Abstract. Introduction: Histopathological definition of bone and joint infection (BJI) is based on Mirra's criterion (≥ 5 polymorphonuclears (PMNs) per field in 5 high power fields (HPFs)). However, this definition does not seem appropriate for chronic BJIs caused by slow-growing germs such as Cutibacterium acnes (C. acnes). The aim of this study was to confirm that Mirra's criterion is not adequate for diagnosis of BJIs due to C. acnes. The second objective was to determine if plasma cell infiltration could be useful for the diagnosis of chronic BJIs due to C. acnes.Methods: We retrospectively selected 25 consecutive patients from 2009 to 2013 with chronic BJIs due to C. acnes. Histological analysis was performed on the 21 cases with at least two C. acnes positive cultures. In addition of Mirra's criterion, the number of plasma cells (≥5 plasma cells/5 HPFs, defined as “CRIOAc Lyon's criterion”) was implemented in the histopathological analysis. Patients were defined as infected, if at least one of the two criteria were present.Results: According to Mirra's and CRIOAc Lyon's criteria, positive histopathology was observed in 12 (57.1%) and 15 (71.4%) cases respectively. Considering the 9 cases with negative Mirra's criterion, high plasma cell infiltration (≥5 plasma cells per field/5 HPFs) was observed in 5 cases (55.6%), and low plasma cells infiltration (2-5 plasma cells per field/5 HPFs) was observed in 4 other cases (44.4%).Conclusions: Adding CRIOAc Lyon's criterion to Mirra's criterion might restore some histopathological diagnosis of chronic BJIs due to C. acnes when a chronic BJI is clinically suspected.