Search

Background: Beyond programmed death ligand 1 (PD-L1), no other biomarkers for immunotherapy are used in daily practice. We previously created EPSILoN (Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)) score, a clinical/biochemical prognostic score, in 154 patients treated with second/further-line immunotherapy. This study's aim was to validate EPSILoN score in a different population group., Methods: 193 patients were included at National Cancer Institute of Milan (second-line immunotherapy, 61%; further-line immunotherapy, 39%). Clinical/laboratory parameters such as neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels were collected. Kaplan-Meier and Cox hazard methods were used for survival analysis., Results: Overall median progression-free survival and median overall survival were 2.3 and 7.6 months, respectively. Multivariate analyses for Progression-Free Survival (PFS) identified heavy smokers (hazard ratio (HR) 0.71, p = 0.036) and baseline LDH < 400 mg/dL (HR 0.66, p = 0.026) as independent positive factors and liver metastases (HR 1.48, p = 0.04) and NLR ≥ 4 (HR 1.49, p = 0.029) as negative prognostic factors. These five factors were included in the EPSILoN score which was able to stratify patients in three different prognostic groups, high, intermediate and low, with PFS of 6.0, 3.8 and 1.9 months, respectively (HR 1.94, p < 0.001); high, intermediate and low prognostic groups had overall survival (OS) of 24.5, 8.9 and 3.4 months, respectively (HR 2.40, p < 0.001)., Conclusions: EPSILoN, combining five baseline clinical/blood parameters (ECOG PS, smoking, liver metastases, LDH, NLR), may help to identify advanced non-small-cell lung cancer (aNSCLC) patients who most likely benefit from immune checkpoint inhibitors (ICIs)., Competing Interests: F.M.d.B.: provided consultation, attended advisory boards and/or provided lectures for the following organizations, from whom received honoraria or education grants: Amgen, AstraZeneca, Boehringer-Ingelheim, B.M.S, Eli Lilly, F. Hoffmann-La Roche, Ignyta, Merck Sharp and Dohme, Merck Serono, Novartis, Pfizer. M.C.G: declares personal financial interests with the following organizations: AstraZeneca, MSD International GmbH, BMS, Boehringer Ingelheim Italia S.p.A, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda; she also declares Institutional financial interests with the following organizations: Eli Lilly, MSD, Pfizer (MISP), AstraZeneca, MSD International GmbH, B.M.S., Boehringer Ingelheim Italia S.p.A, Celgene, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda, Tiziana, Foundation Medicine; at the end, she has received research funding from the following organizations: AIRC, AIFA, Italian Moh, TRANSCAN. G.L.R. declares personal fees from Eli Lilly, B.M.S. and AstraZeneca, outside the submitted work. C.P. declares personal fees from B.M.S. and M.S.D., outside the submitted work. D.S. declares personal fees from AstraZeneca, Boehringer Ingelheim and B.M.S., outside the submitted work. All the authors declare no conflict of interest.

Objectives: Most trials with Immune Checkpoint Inhibitors (ICIs) for Non-Small Cell Lung Cancer (NSCLC) included only small subgroups of patients aged ≥65. As NSCLC is often diagnosed in patients aged ≥70, real-world data about efficacy and safety of immunotherapy (IO) in elderly patients are essential., Materials and Methods: We retrospectively collected data about all patients with advanced NSCLC treated with IO at our Institution between April 2013 and March 2019. The patients were stratified for age as follows: <70 year-old, 70-79 year-old, ≥80 year-old. Chi-square test was used to compare qualitative variables. Survival was estimated with Kaplan-Meier method. Log-rank test was used to compare curves. Multivariate analyses were performed with Cox model., Results: We reviewed 290 cases, with a median age of 67 (range: 29-89). Patients aged<70, 70-79 and ≥80 year-old were 180, 94 and 16, respectively. Clinical/pathological variables were uniformly distributed across age classes, except for a higher rate of males (p 0.0228) and squamous histology (p 0.0071) in the intermediate class. Response Rate (RR) was similar across age groups (p 0.9470). Median Progression Free Survival (PFS) and Overall Survival (OS) did not differ according to age (p 0.2020 and 0.9144, respectively). Toxicity was comparable across subgroups (p 0.6493). The only variables influencing outcome were performance status (PS) (p < 0.0001 for PFS, p 0.0192 for OS), number of metastatic sites (p 0.0842 for PFS, p 0.0235 for OS) and IO line (p < 0.0001 for both PFS and OS)., Conclusion: Advanced age was not associated to a reduced efficacy of IO in our case series. Furthermore, no toxicity concern emerged even among the eldest pts. To our opinion, ICIs should be considered irrespective of age, provided an optimal PS at baseline. Of note, IO is often the only therapeutic option applicable to these cases considering the toxicity of chemotherapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Global loss of biodiversity is an ongoing process that concerns both local and global authorities. Studies of biodiversity mainly involve traditional methods using morphological characters and molecular protocols. However, conventional methods are a time consuming and resource demanding task. The development of high-throughput sequencing (HTS) techniques has reshaped the way we explore biodiversity and opened a path to new questions and novel empirical approaches. With the emergence of HTS, sequencing the complete mitochondrial genome became more accessible, and the number of genome sequences published has increased exponentially during the last decades. Despite the current state of knowledge about the potential of mitogenomics in phylogenetics, this is still a relatively under-explored area for a multitude of taxonomic groups, especially for those without commercial relevance, non-models organisms and with preserved DNA. Here we take the first step to assemble and annotate the genomes from HTS data using a new protocol of genome skimming which will offer an opportunity to extend the field of mitogenomics to under-studied organisms. We extracted genomic DNA from specimens preserved in ethanol. We used Nextera XT DNA to prepare indexed paired-end libraries since it is a powerful tool for working with diverse samples, requiring a low amount of input DNA. We sequenced the samples in two different Illumina platform (MiSeq or NextSeq 550). We trimmed raw reads, filtered and had their quality tested accordingly. We performed the assembly using a baiting and iterative mapping strategy, and the annotated the putative mitochondrion through a semi-automatic procedure. We applied the contiguity index to access the completeness of each new mitogenome. Our results reveal the efficiency of the proposed method to recover the whole mitogenomes of preserved DNA from non-model organisms even if there are gene rearrangement in the specimens. Our findings suggest the potential of combining the adequate platform and library to the genome skimming as an innovative approach, which opens a new range of possibilities of its use to obtain molecular data from organisms with different levels of preservation., Competing Interests: Daniel J. Lahr is an Academic Editor for PeerJ., (©2019 Trevisan et al.)

Tapeworms of the genus Anindobothrium Marques, Brooks & Lasso, 2001 are found in both marine and Neotropical freshwater stingrays of the family Potamotrygonidae. The patterns of host association within the genus support the most recent hypothesis about the history of diversification of potamotrygonids, which suggests that the ancestor of freshwater lineages of the Potamotrygonidae colonized South American river systems through marine incursion events. Despite the relevance of the genus Anindobothrium to understand the history of colonization and diversification of potamotrygonids, no additional efforts were done to better investigate the phylogenetic relationship of this taxon with other lineages of cestodes since its erection. This study is a result of recent collecting efforts to sample members of the genus in marine and freshwater potamotrygonids that enabled the most extensive documentation of the fauna of Anindobothrium parasitizing species of Styracura de Carvalho, Loboda & da Silva, Potamotrygon schroederi Fernández-Yépez, P. orbignyi (Castelnau) and P. yepezi Castex & Castello from six different countries, representing the eastern Pacific Ocean, Caribbean Sea, and river basins in South America (Rio Negro, Orinoco, and Maracaibo). The newly collected material provided additional specimens for morphological studies and molecular samples for subsequent phylogenetic analyses that allowed us to address the phylogenetic position of Anindobothrium and provide molecular and morphological evidence to recognize two additional species for the genus. The taxonomic actions that followed our analyses included the proposition of a new family, Anindobothriidae fam. n., to accommodate the genus Anindobothrium in the order Rhinebothriidea Healy, Caira, Jensen, Webster & Littlewood, 2009 and the description of two new species-one from the eastern Pacific Ocean, A. carrioni sp. n., and the other from the Caribbean Sea, A. inexpectatum sp. n. In addition, we also present a redescription of the type species of the genus, A. anacolum (Brooks, 1977) Marques, Brooks & Lasso, 2001, and of A. lisae Marques, Brooks & Lasso, 2001. Finally, we discuss the paleogeographical events mostly linked with the diversification of the genus and the protocols adopted to uncover cryptic diversity in Anindobothrium.