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Background Extended RAS analysis is mandatory in metastatic colorectal cancer (mCRC) patients. The optimal threshold of RAS mutated subclones to identify patients most likely to benefit from antiepidermal growth factor receptor (EGFR) therapy is controversial. Our aim was to assess the clinical impact of detecting mutations in RAS, BRAF, PIK3CA and EGFRS492R in basal tissue tumour samples by using a highly sensitive next-generation sequencing (NGS) technology in mCRC patients treated with chemotherapy plus anti-EGFR or anti-vascular endothelial growth factor. Patients and methods Five hundred and eighty-one tumour samples from untreated mCRC patients from 7 clinical studies were collected. Mutational analysis was carried out by standard-of-care (therascreen pyro) with a sensitivity detection of 5% mutant allele fraction (MAF), and compared with NGS technology using 454GS Junior platform (Roche Applied Science, Germany) with a sensitivity of 1%. Molecular results were correlated with clinical outcomes. Results After quality assessment, 380 samples were evaluable for molecular analysis. Standard-of-care mutational analysis detected RAS, BRAFV600E or PIK3CA mutations in 56.05% of samples compared with 69.21% by NGS (P  =   0.00018). NGS identified coexistence of multiple low-frequency mutant alleles in 96 of the 263 mutated cases (36.5%; range 2–7). Response rate (RR), progression-free survival (PFS) and overall survival (OS) were increasingly improved in patients with RAS wild-type, RAS/BRAF wild-type or quadruple (KRAS/NRAS/BRAF/PIK3CA) wild-type tumours treated with anti-EGFR, assessed by standard-of-care. No additional benefit in RR, PFS or OS was observed by increasing the detection threshold to 1% by NGS. An inverse correlation between the MAF of the most prevalent mutation detected by NGS and anti-EGFR response was observed (P  =   0.039). EGFR S492R mutation was not detected in untreated samples. Conclusions No improvement in the selection of patients for anti-EGFR therapy was obtained by adjusting the mutation detection threshold in tissue samples from 5% to 1% MAF. Response to anti-EGFR was significantly better in patients with quadruple wild-type tumours. [ABSTRACT FROM AUTHOR]

Background: We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC)., Patients and Methods: VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and <3 circulating tumour cells/7.5 ml blood were stratified by BRAF/PIK3CA status (wild-type versus mutated) and number of affected organs (1 versus >1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m 2 then 250 mg/m 2 weekly) plus FOLFIRI [irinotecan 180 mg/m 2 , leucovorin 400 mg/m 2 , 5-fluorouracil 400 mg/m 2 (bolus) then 2400 mg/m 2 (46-h continuous infusion) every 2 weeks]. The primary endpoint was progression-free survival (PFS). All analyses were exploratory., Results: Two hundred and forty patients with BRAF/PIK3CA wild-type (n = 196) or BRAF- and/or PIK3CA-mutated tumours (n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF/PIK3CA wild-type and BRAF/PIK3CA-mutated tumours, respectively [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602]. In the BRAF- and/or PIK3CA-mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF/PI3KCA-mutated (n = 8), BRAF-mutated/PI3KCA wild-type (n = 16) and BRAF wild-type/PI3KCA-mutated (n = 20) tumours, respectively (P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF/PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF/PIK3CA-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups., Conclusions: BRAF/PIK3CA status influences outcomes in patients with RAS wild-type mCRC but does not appear to assist with the selection of first-line targeted therapy., Competing Interests: Disclosure JS has done speaking honoraria for Ipsen, Lilly, Merck, MSD, Pfizer, Roche, Shire and Servier, advisory roles for Amgen, Bayer, Bristol-Myers Squibb, Celgene, Ipsen, Merck, Roche, Sanofi and Servier, and received travelling and accommodation support from Ipsen and Merck. JMV reports grants, personal fees, non-financial support and other from Roche, non-financial support and other from Amgen, and non-financial support from Servier, Bristol-Myers Squibb, BTG and Sanofi outside the submitted work. JJR-Z has done consulting or advisory roles for Amgen, Archimedes, Bayer, Ipsen, Merck, Novartis, Pfizer, Prostrakan, Roche, Sanofi and Servier, and received travel, accommodation and expenses from Amgen, Bayer, Ipsen, Merck, Novartis, Prostrakan, Roche, Sanofi and Servier. MJS has done consulting or advisory roles for Amgen, Merck, Roche, Sanofi and Servier, and received travel, accommodation and expenses from Amgen, Merck and Roche. ALC has received travel, accommodation and expenses from Amgen. EP has done speaking honoraria for Amgen, Ipsen, Servier, Roche, Merck, Sanofi and received travel and accommodation from Merck, Roche, Ipsen, Novartis and Amgen. EAM has done advisory roles for Amgen, Roche, Merck, Bayer and Servier, speaking honoraria for Lilly, Roche and Amgen, and travel and accommodation from Roche, Amgen, Merck, Lilly and Servier. BGP reports personal fees and non-financial support from Sanofi, personal fees from Amgen, Advanced Accelerator Applications, Ipsen Pharma and Merck Serono, personal fees and non-financial support from Servier, Roche and Novartis outside the submitted work. RLL has stock and other ownership interests in MTrap and Nasasbiotech SL, has done consulting or advisory roles for Bayer, Bristol-Myers Squibb, Janssen, Lilly, MSD and Roche, done speakers' bureaus for Novartis and Roche, received institutional research funding from Lilly, Merck and Roche, and received travel, accommodation and expenses from Pierre Fabre, Roche and Tesaro. EA has done consulting or advisory roles for Amgen, Bayer, Celgene, Merck, Roche and Sanofi. EDR has done consulting or advisory roles for Amgen, Bayer, Genomica, Merck Serono and Servier, speakers' bureaus for MSD and Servier, and received research funding from Amgen, AstraZeneca, Merck Serono, Roche and Sysmex. PGA, MTC, FR, AS, GQ, LRD, SG, MG and MVA declare no competing interests. Data sharing The study data (i.e. de-identified participant data and datasets analysed for the present manuscript) are available from the corresponding author, Dr J. Sastre (e-mail: jsastrev@salud.madrid.org), on reasonable request and subject to approval from the lead investigators. Additional, related documents will also be available (study protocol, statistical analysis plan, informed consent form)., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Eighteen sandy beaches were sampled along the 1659 km of the Galician coast (NW Spain) six months after the Prestige oil-spill to study the impact of the fuel and the clean-up activities on the macroinfauna community. A transect was extended at each beach, from above the drift line to below the swash line at five sampled levels; at each level six 0.05 m2 replicates were taken to a depth of 30 cm and sieved through a 1mm mesh, and the organisms collected and preserved. Results were compared with previous data obtained using the same procedures. The macroinfauna was numerically dominated by the amphipod Pontocrates arenarius, the isopod genus Eurydice, the polychaete Scolelepis squamata, and the amphipod Talitrus saltator. As a result of the Prestige oil-spill and the clean-up activities, beach populations were reduced, with Eurydice and S. squamata as the most affected taxa.

Five species of polychaetes (Spionidae) were found associated to Thalassia testudinum meadows in Parque Nacional Morrocoy, Venezuela. We included a guide for their identification and present range extensions for the Venezuelan coasts and Southern Caribbean Sea. The species are: Dipolydora socialis, Prionospio (Minuspio) cirrifera, P. (Prionospio) fallax, P. (P.) steenstrupi, and Spio pettiboneae.