Cancer molecular heterogeneity might explain the variable response of EGFR mutant lung adenocarcinomas to tyrosine kinase inhibitors (TKIs). We assessed the mutational status of 22 cancer genes by next-generation sequencing (NGS) in poor, intermediate or good responders to first-line gefitinib. Clinical outcome was correlated with Additional Coexisting Mutations (ACMs) and the EGFR Proportion of Mutated Alleles (PMA). Thirteen ACMs were found in 10/17 patients: TP53 (n=6), KRAS (n=2), CTNNB1 (n=2), PIK3CA, SMAD4 and MET (n=1 each). TP53 mutations were exclusive of poor/intermediate responders (66.7% versus 0, p=0.009). Presence of ACMs significantly affected both PFS (median 3.0 versus 12.3 months, p=0.03) and survival (3.6 months versus not reached, p=0.03). TP53 mutation was the strongest negative modifier (median PFS 4.0 versus 14.0 months). Higher EGFR PMA was present in good versus poor/intermediate responders. Median PFS and survival were longer in patients with EGFR PMA ≥0.36 (12.0 versus 4.0 months, p=0.31; not reached versus 18.0 months, p=0.59). Patients with an EGFR PMA ≥0.36 and no ACMs fared significantly better (p=0.03), with a trend towards increased survival (p=0.06). Our exploratory data suggest that a quantitative (PMA) and qualitative (ACMs) molecular heterogeneity assessment using NGS might be useful for a better selection of patients.

Purpose -3D printing (3DP), which is technically known as additive manufacturing, is being increasingly used for the development of bespoke products within a broad range of commercial contexts. The purpose of this paper is to investigate the potential for this technology to be used in support of the preparation and response to a natural disaster or complex emergency and as part of developmental activities, and to offer a number of key insights following a pilot trial based in the East African HQ of a major international non-governmental organisation. Design/methodology/approach -Using an illustrative example from the water, sanitation and hygiene (WASH) field this paper demonstrates, from both a theoretical and practical standpoint, how 3DP has the potential to improve the efficiency and effectiveness of humanitarian logistic (HL) operations. Findings -Based on the pilot trial, the paper confirms that the benefits of 3DP in bespoke commercial contextsincluding the reduction of supply chain lead times, the use of logistic postponement techniques and the provision of customised solutions to meet unanticipated operational demandsare equally applicable in a humanitarian environment. It also identifies a number of key challenges that will need to be overcome in the operationalisation of 3DP in a development/disaster response context, and proposes a hub-and-spoke modelwith the design and testing activities based in the hub supporting field-based production at the spokesto mitigate these. Research limitations/implications -In addition to an extensive review of both the HL and additive manufacturing literature, the results of the pilot trial of 3DP in support of humanitarian operations, are reported. The paper recommends further detailed analysis of the underpinning cost model together with further field trials of the recommended organisational construct and testing of the most appropriate materials for a given artefact and environment. Practical implications -3DP has the potential to improve the response to disasters and development operations through the swift production of items of equipment or replacement spare parts. With low capital and running costs, it offers a way of mitigating delays in the supply chain through on site fabrication to meet an identified requirement more swiftly and effectively than via the traditional re-supply route, and it allows for adaptive design practice as multiple iterations of a product are possible in order to optimise the design based on field testing. Social implications -The logistic challenges of responding in a disaster affected or development environment are well documented. Successful embodiment of 3DP as part of the humanitarian logistician's portfolio of operational techniques has the potential to deliver more efficient and effective outcomes in support of the beneficiaries as well as a sense of empowerment in relation to problem solving. In addition, it has the longer term potential for the creation of a new industry (and, hence, income source) for those living in remote loca...

ALK translocation may be found in lung pure squamous cell carcinomas. Our data suggest the opportunity to test ALK rearrangements on biopsy samples harboring squamous cell cancer differentiation.