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Aim: This study sought to evaluate the effectiveness of lactate/albumin ratio for ICU mortality prediction in a large cohort of patients with severe Coronavirus Disease-2019 (COVID-19) admitted to an intensive care unit (ICU). Methods: This is a single-center retrospective cohort study of prospectively collected data derived from the COVID-19 dataset for all critically ill patients admitted to an academic ICU. Data were used to determine the relation between lactate/albumin ratio and other laboratory parameters measured on the first day of the ICU stay and to evaluate the prognostic performance for ICU mortality prediction. Results: A total of 805 ICU patients were included, and the median age (IQR) was 67 (57-76) years, with 68% being male. ICU mortality was 48%, and the median lactate/albumin ratio was 0.53 (0.39-0.59). A survival analysis showed that patients with higher lactate/albumin ratio values had significantly lower survival rates (Log Rank p < 0.001). A multivariable analysis revealed that the lactate/albumin ratio was an independent risk factor for ICU mortality with a hazard ratio of 1.39 (CI: 1.27-1.52). The lactate/albumin ratio showed a receiver operating characteristics area under the curve (ROC-AUC) value to predict ICU mortality significantly higher than that of lactate alone (0.71 vs. 0.68, DeLong test p < 0.001). The optimal lactate/albumin ratio cut-off for predicting ICU mortality was 0.57, with 63% sensitivity and 73% specificity. A subgroup analysis revealed that the lactate/albumin ratio was significantly associated with mortality across different patient groups, including age and sex categories, and those with or without hypertension and coronary heart disease. Conclusions : Lactate/albumin ratio is a reliable prognostic marker in critically ill COVID-19 patients and could predict ICU mortality more accurately than lactate alone.

Purpose: The ETOP 10-16 BOOSTER study was a randomized phase II trial of osimertinib and bevacizumab therapy versus osimertinib therapy in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously., Experimental Design: Next-generation sequencing (Guardant360) was conducted in serial plasma samples. The association between ctDNA and efficacy outcomes was explored, and molecular alterations at progression were described., Results: A total of 136 patients (88% of 155 randomized) had plasma samples at baseline (68 per arm), 110 (71%) at week 9, and 65 (42%) at progression. In a multivariable model for progression-free survival (PFS), the treatment effect was found to differ by smoking status (interaction P = 0.046), with the effect of smoking also differing by baseline EGFR T790M (interaction P = 0.033), whereas both TP53 at baseline and the tissue EGFR exon 21 L858R mutation were significantly associated with worse PFS outcome. Smokers (current/former) without baseline EGFR T790M showed a significant improvement in PFS under combination treatment, albeit with small numbers (P = 0.015). Week-9 EGFR T790M clearance was associated with improved PFS in the osimertinib arm (P = 0.0097). Acquired EGFR C797S mutations were detected in 22% and 13% of patients in the combination and osimertinib arms, respectively., Conclusions: The differential effect of treatment by smoking was not explained by TP53 mutations or other molecular alterations examined. Molecular mechanisms of acquired resistance were detected, but no novel molecular alterations were identified in the combination arm., (©2024 American Association for Cancer Research.)

Background: The aim of this study was to investigate the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte count ratio (NLR), and their combination, in distinguishing candidemia from bacteremia in intensive care unit (ICU) patients. Methods: This is a retrospective study in ICU patients with documented bloodstream infections (BSIs) and with both serum PCT and CRP measurements on the day of the positive blood sample. Illness severity was assessed by sequential organ failure assessment (SOFA) score on both admission and BSI day. Demographic, clinical, and laboratory data, including PCT and CRP levels and NLR on the day of the BSI, were recorded. Results: A total of 63 patients were included in the analysis, of whom 32 had bacteremia and 31 had candidemia. PCT, CRP, and NLR values were all significantly lower in candidemia compared with bacteremia (0.29 (0.14-0.69) vs. 1.73 (0.5-6.9) ng/mL, p < 0.001, 6.3 (2.4-11.8) vs. 19 (10.7-24.8) mg/dl, p < 0.001 and 6 (3.7-8.6) vs. 9.8 (5.3-16.3), p = 0.001, respectively). PCT was an independent risk factor for candidemia diagnosis (OR 0.153, 95%CI: 0.04-0.58, p = 0.006). A multivariable model consisting of the above three variables had better predictive ability (AUC-ROC = 0.88, p < 0.001), for candidemia diagnosis, as compared to that of PCT, CRP, and NLR, whose AUC-ROCs were all lower (0.81, p < 0.001, 0.78, p < 0.001, and 0.68, p = 0.015, respectively). Conclusions: A combination of routinely available laboratory tests, such as PCT, CRP, and NLR, could prove useful for the early identification of ICU patients with candidemia.

Purpose: Emergency laparotomy (EL) is a common operation with high risk for postoperative complications, thereby requiring accurate risk stratification to manage vulnerable patients optimally. We developed and internally validated a predictive model of serious complications after EL., Methods: Data for eleven carefully selected candidate predictors of 30-day postoperative complications (Clavien-Dindo grade >  = 3) were extracted from the HELAS cohort of EL patients in 11 centres in Greece and Cyprus. Logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) was applied for model development. Discrimination and calibration measures were estimated and clinical utility was explored with decision curve analysis (DCA). Reproducibility and heterogeneity were examined with Bootstrap-based internal validation and Internal-External Cross-Validation. The American College of Surgeons National Surgical Quality Improvement Program's (ACS-NSQIP) model was applied to the same cohort to establish a benchmark for the new model., Results: From data on 633 eligible patients (175 complication events), the SErious complications After Laparotomy (SEAL) model was developed with 6 predictors (preoperative albumin, blood urea nitrogen, American Society of Anaesthesiology score, sepsis or septic shock, dependent functional status, and ascites). SEAL had good discriminative ability (optimism-corrected c-statistic: 0.80, 95% confidence interval [CI] 0.79-0.81), calibration (optimism-corrected calibration slope: 1.01, 95% CI 0.99-1.03) and overall fit (scaled Brier score: 25.1%, 95% CI 24.1-26.1%). SEAL compared favourably with ACS-NSQIP in all metrics, including DCA across multiple risk thresholds., Conclusion: SEAL is a simple and promising model for individualized risk predictions of serious complications after EL. Future external validations should appraise SEAL's transportability across diverse settings., (© 2023. The Author(s).)

Although coronavirus disease 2019 (COVID-19)-induced changes in laboratory parameters in patients upon admission have been well-documented, information on their temporal changes is limited. The present study describes the laboratory trends and the effect of dexamethasone treatment on these parameters, in patients with COVID-19 in the intensive care unit (ICU). Routine laboratory parameters, namely white blood cell (WBC), neutrophil, lymphocyte and platelet (PLT) counts, fibrinogen, C-reactive protein (CRP), lactate dehydrogenase (LDH) and albumin concentrations, were recorded upon admission to the ICU and, thereafter, on days 3, 5, 10, 15 and 21; these values were compared between survivors and non-survivors, as well as between those who were treated with dexamethasone and those who were not. Among the 733 patients in the ICU, (mean age, 65±13 years; 68% males; ICU mortality rate 45%; 76% of patients treated with dexamethasone), the WBC and neutrophil counts were persistently high in all patients, without significant differences over the first 15 days. Initially, low lymphocyte counts exhibited increasing trends, but remained higher in survivors compared to non-survivors (P=0.01). The neutrophil-to-lymphocyte ratio (NLR) was persistently elevated in all patients, although it was significantly higher in non-survivors compared to survivors (P < 0.001). The PLT count was initially increased in all patients, although it was significantly decreased in non-survivors over time. The fibrinogen and LDH values remained similarly elevated in all patients. However, the increased levels of CRP, which did not differ between patients upon admission, further increased in non-survivors compared to survivors after day 10 (P=0.001). Declining trends in albumin levels over time, overall, with a significant decrease in non-survivors compared to survivors, were observed. Dexamethasone treatment significantly affected the temporal progression of fibrinogen and CRP in survivors and that of NLR in non-survivors. On the whole, the present study demonstrates that patients in the ICU with COVID-19 present persistently abnormal laboratory findings and significant differences in laboratory trends of NLR, CRP, PLT and albumin, but not in WBC and neutrophil count, and fibrinogen and LDH levels, between survivors and non-survivors. The temporal progression of fibrinogen, CRP and NLR is affected by dexamethasone treatment., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Kokkoris et al.)

Introduction: Pleural mesothelioma (PM) is an aggressive malignancy with increasing prevalence and poor prognosis. Real-life data are a unique approach to reflect the reality of PM epidemiology, treatment, and prognosis in Europe., Methods: A joint analysis of the European Thoracic Oncology Platform Mesoscape and the European Society of Thoracic Surgeons (ESTS) databases was performed to better understand the characteristics and epidemiology of PM, including histologic subtype, staging, and treatment. Overall survival (OS) was assessed, adjusting for parameters of clinical interest., Results: The analysis included 2766 patients (Mesoscape: 497/10 centers/ESTS: 2269/77 centers). The primary histologic subtype was epithelioid (71%), with 57% patients on stages III to IV. Within Mesoscape, the patients received either multimodality (59%) or palliative intention treatment (41%). The median follow-up was 47.2 months, on the basis of 1103 patients (Mesoscape: 491/ESTS: 612), with 823 deaths, and median OS was 17.4 months. In multivariable analysis, female sex, epithelioid subtype, and lower stage were associated with longer OS, when stratifying by cohort, age, and Eastern Cooperative Oncology Group Performance Status. Within Mesoscape, multimodality treatment including surgery was predictive of longer OS (hazard ratio = 0.56, 95% confidence interval: 0.45-0.69), adjusting for sex, histologic subtype, and Eastern Cooperative Oncology Group Performance Status. Overall, surgical candidates with a macroscopic complete resection had a significantly longer median OS compared with patients with R2 (25.2 m versus 16.4 m; log-rank p < 0.001)., Conclusions: This combined European Thoracic Oncology Platform/ESTS database analysis offers one of the largest databases with detailed clinical and pathologic outcome. Our finding reflects a benefit for selected patients that undergo multimodality treatment, including macroscopic complete resection, and represents a valuable resource to inform the epidemiology and treatment options for individual patients., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Accurate preoperative risk assessment in emergency laparotomy (EL) is valuable for informed decision making and rational use of resources. Available risk prediction tools have not been validated adequately across diverse health care settings. Herein, we report a comparative external validation of four widely cited prognostic models., Methods: A multicenter cohort was prospectively composed of consecutive patients undergoing EL in 11 Greek hospitals from January 2020 to May 2021 using the National Emergency Laparotomy Audit (NELA) inclusion criteria. Thirty-day mortality risk predictions were calculated using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), NELA, Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (P-POSSUM), and Predictive Optimal Trees in Emergency Surgery Risk tools. Surgeons' assessment of postoperative mortality using predefined cutoffs was recorded, and a surgeon-adjusted ACS-NSQIP prediction was calculated when the original model's prediction was relatively low. Predictive performances were compared using scaled Brier scores, discrimination and calibration measures and plots, and decision curve analysis. Heterogeneity across hospitals was assessed by random-effects meta-analysis., Results: A total of 631 patients were included, and 30-day mortality was 16.3%. The ACS-NSQIP and its surgeon-adjusted version had the highest scaled Brier scores. All models presented high discriminative ability, with concordance statistics ranging from 0.79 for P-POSSUM to 0.85 for NELA. However, except the surgeon-adjusted ACS-NSQIP (Hosmer-Lemeshow test, p = 0.742), all other models were poorly calibrated ( p < 0.001). Decision curve analysis revealed superior clinical utility of the ACS-NSQIP. Following recalibrations, predictive accuracy improved for all models, but ACS-NSQIP retained the lead. Between-hospital heterogeneity was minimum for the ACS-NSQIP model and maximum for P-POSSUM., Conclusion: The ACS-NSQIP tool was most accurate for mortality predictions after EL in a broad external validation cohort, demonstrating utility for facilitating preoperative risk management in the Greek health care system. Subjective surgeon assessments of patient prognosis may optimize ACS-NSQIP predictions., Level of Evidence: Diagnostic Test/Criteria; Level II., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Emergency laparotomy (EL) is accompanied by high post-operative morbidity and mortality which varies significantly between countries and populations. The aim of this study is to report outcomes of emergency laparotomy in Greece and to compare them with the results of the National Emergency Laparotomy Audit (NELA)., Methods: This is a multicentre prospective cohort study undertaken between 01.2019 and 05.2020 including consecutive patients subjected to EL in 11 Greek hospitals. EL was defined according to NELA criteria. Demographics, clinical variables, and post-operative outcomes were prospectively registered in an online database. Multivariable logistic regression analysis was used to identify independent predictors of post-operative mortality., Results: There were 633 patients, 53.9% males, ASA class III/IV 43.6%, older than 65 years 58.6%. The most common operations were small bowel resection (20.5%), peptic ulcer repair (12.0%), adhesiolysis (11.8%) and Hartmann's procedure (11.5%). 30-day post-operative mortality reached 16.3% and serious complications occurred in 10.9%. Factors associated with post-operative mortality were increasing age and ASA class, dependent functional status, ascites, severe sepsis, septic shock, and diabetes. HELAS cohort showed similarities with NELA patients in terms of demographics and preoperative risk. Post-operative utilisation of ICU was significantly lower in the Greek cohort (25.8% vs 56.8%) whereas 30-day post-operative mortality was significantly higher (16.3% vs 8.7%)., Conclusion: In this study, Greek patients experienced markedly worse mortality after emergency laparotomy compared with their British counterparts. This can be at least partly explained by underutilisation of critical care by surgical patients who are at high risk for death., (© 2022. The Author(s).)

Background: As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer., Methods: In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19., Findings: The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR 30 ) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR 30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p<0.0001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.0030), COVID-19 complication rate (11.9% vs 34.6%, p=0.0040), with a reduced need for COVID-19-specific therapy (26.3% vs 57.9%, p=0.0004) compared with unvaccinated patients. Inverse probability of treatment weighting (IPTW)-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated patients experienced a decreased risk of death at 30 days (adjusted OR, aOR 0.08, 95% CI 0.01 to 0.69).Overall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR 30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 10 9  cells/L, p=0.0098)., Conclusion: Anti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2., Competing Interests: Competing interests: KJH declares research funding from AstraZeneca, Boehringer-Ingelheim, MSD, Replimune and advisory board fees/honoraria from Arch Oncology, AstraZeneca, BMS, Boehringer-Ingelheim, Codiak Biosciences, Inzen Therapeutics, Merck-Serono, MSD, Pfizer, Replimune. DA reports consultation/advisory role for AstraZeneca, Bristol Myers Squibb, Merck Sharp reports speaker’s engagement from AstraZeneca, Bristol Myers Squibb, Merck Sharp reports serving as local PI for Bristol Myers Squibb, Pierre Fabre Pharma and coordinating PI for OncoLytics; reports grant funding from AbbVie; reports being/been DSMB chair of Sanofi (Genzyme); reports being/been a steering committee member of Roche. Olivier Michielin reports personal fees from Bristol-Myers Squibb, MSD, Novartis, Roche, Amgen, NeraCare, outside the submitted work. JR received speaker or advisory fees from Roche, Astra Zeneca, Merck, Ferrer, Persan Farma, Teva Pharma, Leo Pharma, Fresenius kabi, MSD, BMS. Travel expenses support from BMS, MSD, RocheUrania Dafni reports honorarium as Member of the Tumor Agnostic Evidence Generation Working Group of Roche, outside the submitted work. GP reports grants from Amgen, Lilly; grants, personal fees and nonfinancial support from Merck; grants and non-financial support from AstraZeneca; grants and personal fees from Roche, Bristol Myers Squibb, MSD, Novartis, outside the submitted work. Solange Peters reports consultation/advisory role for AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol- Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody; talk in a company’s organized public event for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda; receipt of grants/research supports from being a (sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics. Emanuela Rromano reports investigator-initiated trial (funds paid to the institution) supported by Astra-Zeneca, BMS; serves on the consultancy/advisory board for Astra-Zeneca, Merck, Roche, Pierre Fabre. ML acted as consultant for Roche, Novartis, Lilly, AstraZeneca, Exact Sciences, MSD, Pfizer, Seagen and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, Ipsen and Sandoz outside the submitted work.Alessandra Gennari has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, EISAI, and Daichii Sankyo; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; research funds: EISAI, Eli Lilly, and Roche. CMV has received travel grants and other honoraria from BMS, MSD, Novartis and Roche. Joan Brunet has declared consulting/advisory role for MSD and Astra Zeneca. Aleix Prat has declared personal honoraria from Pfizer, Roche, MSD Oncology, Eli Lilly, and Daiichi Sankyo; travel, accommodations, and expenses paid by Daiichi Sankyo; research funding from Roche and Novartis; and consulting/advisory role for NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb. Mark Bower received speakers’ fee from EISAI pharma, Gilead Sciences, Merck and ViiV. JT reports consulting fees from Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Scandion Oncology, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, and TheraMyc; speaker’s fees from Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource; and institutional research support from Amgen, Array Biopharma, AstraZeneca Pharmaceuticals, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma International, Janssen-Cilag, MedImmune, Menarini, Merck Health, Merck Sharp and has had leadership roles in the European AIDS Clinical Society, UNAIDS, WHO, and The European Hematology Association/ European Society of Medical Oncology. DJP received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, EISAI, Falk Foundation, travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, DaVolterra and Astra Zeneca; research funding (to institution) from MSD and BMS. AC received consulting fees from MSD, BMS, AstraZeneca, Roche; speakers’ fee from AstraZeneca, MSD, Novartis and Eisai. All remaining authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4 + and CD8 + T cells. LDRT elicited predominantly CD4 + cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and immune checkpoint blockade to patients with immune-desert tumors. In responsive patients, the combinatorial treatment triggered T-cell infiltration, predominantly of CD4 + cells with Th1 signatures. Our data support the rational combination of LDRT with immunotherapy for effectively treating low T cell-infiltrated tumors. SIGNIFICANCE: Low-dose radiation reprogrammed the tumor microenvironment of tumors with scarce immune infiltration and together with immunotherapy induced simultaneous mobilization of innate and adaptive immunity, predominantly CD4 + effector T cells, to achieve tumor control dependent on NKG2D. The combination induced important responses in patients with metastatic immune-cold tumors. This article is highlighted in the In This Issue feature, p. 1 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Introduction: KRAS mutations, the most frequent gain-of-function alterations in NSCLC, are currently emerging as potential predictive therapeutic targets. The role of KRAS-G12C (Kr&#95;G12C) is of special interest after the recent discovery and preclinical analyses of two different Kr&#95;G12C covalent inhibitors (AMG-510, MRTX849)., Methods: KRAS mutations were evaluated in formalin-fixed, paraffin-embedded tissue sections by a microfluidic-based multiplex polymerase chain reaction platform as a component of the previously published European Thoracic Oncology Platform Lungscape 003 Multiplex Mutation study, of clinically annotated, resected, stage I to III NSCLC. In this study, -Kr&#95;G12C mutation prevalence and its association with clinicopathologic characteristics, molecular profiles, and postoperative patient outcome (overall survival, relapse-free survival, time-to-relapse) were explored., Results: KRAS gene was tested in 2055 Lungscape cases (adenocarcinomas: 1014 [49%]) with I or II or III stage respective distribution of 53% or 24% or 22% and median follow-up of 57 months. KRAS mutation prevalence in the adenocarcinoma cohort was 38.0% (95% confidence interval (CI): 35.0% to 41.0%), with Kr&#95;G12C mutation representing 17.0% (95% CI: 14.7% to 19.4%). In the "histologic-subtype" cohort, Kr&#95;G12C prevalence was 10.5% (95% CI: 9.2% to 11.9%). When adjusting for clinicopathologic characteristics, a significant negative prognostic effect of Kr&#95;G12C presence versus other KRAS mutations or nonexistence of KRAS mutation was identified in the adenocarcinoma cohort alone and in the "histologic-subtype" cohort. For overall survival in adenocarcinomas, hazard ratio (HR) G12C versus other KRAS is equal to 1.39 (95% CI: 1.03 to 1.89, p = 0.031) and HR G12C versus no KRAS is equal to 1.32 (95% CI: 1.03 to 1.69, p = 0.028) (both also significant in the "histologic-subtype" cohort). For time-to-relapse, HR G12C versus other KRAS is equal to 1.41 (95% CI: 1.03 to 1.92, p = 0.030). In addition, among all patients, for relapse-free survival, HR G12C versus no KRAS is equal to 1.27 (95% CI: 1.04 to 1.54, p = 0.017)., Conclusions: In this large, clinically annotated stage I to III NSCLC cohort, the specific Kr&#95;G12C mutation is significantly associated with poorer prognosis (adjusting for clinicopathologic characteristics) among adenocarcinomas and in unselected NSCLCs., (Copyright © 2021 International Association for the Study of Lung Cancer. All rights reserved.)