tbuckley/cabot-search huggingface dataset:
CD40 agonist-induced IL-12p40 potentiates hepatotoxicity
Authors: Caroline Bonnans, Graham Thomas, Wenqian He, Breanna Jung, Wei Chen, Min Liao, Jonathan Heyen, Bernard Buetow, Smitha Pillai, Diane Matsumoto, Javier Chaparro-Riggers, Shahram Salek-Ardakani, Yan Qu
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background CD40 is a compelling target for cancer immunotherapy, however, attempts to successfully target this pathway have consistently been hampered by dose-limiting toxicity issues in the clinic that prevents the administration of efficacious doses. Methods Here, using cytokine and cytokine receptor depletion strategies in conjunction with a potent CD40 agonist, we investigated mechanisms underlying the two primary sources of CD40 agonist-associated toxicity, hepatotoxicity and cytokine release syndrome (CRS). Results We demonstrate that CD40 agonist -induced hepatotoxicity and CRS are mechanistically independent. Historical data have supported a role for interleukin-6 (IL-6) in CRS-associated wasting, however, our findings instead show that an inflammatory cytokine network involving TNF, IL-12p40, and IFNγ underlie this process. Deficiency of TNF or IFNγ did not influence CD40-induced hepatitis however loss of IL-12p40 significantly decreased circulating concentrations of liver enzymes and reduced the frequency of activated CD14 + MHCII + myeloid cells in the liver, indicating a role for IL-12p40 in liver pathology. Conclusions As clinical research programs aim to circumnavigate toxicity concerns while maintaining antitumor efficacy it will be essential to understand which features of CD40 biology mediate antitumor function to develop both safe and efficacious agonists.
Spironolactone dose in heart failure with preserved ejection fraction: findings from <scp>TOPCAT</scp>
Authors: João Pedro Ferreira, Xavier Rossello, Stuart J. Pocock, Patrick Rossignol, Brian L. Claggett, Jean‐Lucien Rouleau, Scott D. Solomon, Bertram Pitt, Marc A. Pfeffer, Faiez Zannad
Journal: European Journal of Heart Failure (2020)
Single nucleotide polymorphisms (SNPs) as predictors of efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Daniel Herrero Rivera, Ignacio Duran, Laura Marcos Kovandzic, Javier Puente, Begona Mellado, Enrique Grande, Juan Antonio Virizuela, Juan Francisco Rodriguez-Moreno, Ainara Azueta, Lucia Andrea Alonso Buznego, Raquel Luque, Carmen Garrigos
Journal: Journal of Clinical Oncology (2020)

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p&lt;0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.
Analytical validation of digital cytometry (iSort) for leukocyte enumeration using stored blood.
Authors: Aaron M. Newman, Aki Nakao, Kathy Li, Chih-Long Liu, Kavita Mathi, Natalia Sigal, Holden Maecker, Maximilian Diehn, Ash A. Alizadeh
Journal: Journal of Clinical Oncology (2020)

3542 Background: Blood leukocyte enumeration is a cornerstone for clinical diagnosis and immune monitoring of diverse cancers and immunotherapies. Existing methods rely on intact/living cells and can thus be limiting due to handling time constraints and need for predefined antibody panels. While indirect cytometry methods including digital cytometry can overcome this limitation on archival specimens, their clinical performance has not been extensively characterized. We developed iSort, a novel transcriptome deconvolution method based on CIBERSORTx. Here, we comprehensively evaluated iSort and validated it against established diagnostic standards. Methods: We recruited 36 healthy adult blood donors and characterized their blood leukocyte profiles. We used several established clinical cytometry methods requiring intact cells in a CLIA laboratory including Complete Blood Count [CBC] and 6-color TBNK [TBNK]. We also immunophenotyped leukocytes by a research flow cytometry panel (FACS) and by mass cytometry (CyTOF). We then used these techniques as standards for validating leukocyte populations enumerated by iSort. iSort was performed on whole blood through deconvolution of 22 subsets from RNA-Seq. We assessed iSort’s analytical detection performance by spiking purified lymphocyte subsets into lymphodepleted human blood and by simulating blood mixtures using defined leukocyte mixtures within latin square designs. We assessed iSort concordance with an FDA approved IVD assay (TBNK) comparing distinct RNA-Seq library preparation chemistries. Results: iSort was highly correlated with TBNK/CBC across CD4 T, CD8 T, B cells, NK cells, monocytes, and neutrophils (r≥0.95). When comparing correlations to TBNK/CBC, we found no significant differences between iSort, CyTOF, and FACS, nor between RNA-Seq library chemistries. iSort demonstrated high linearity at low abundance levels (0.1 - 1%, r = 0.99, B-cells spiked into lymphodepleted blood samples after Rituximab) and at higher abundance levels (0.5 - 90%, r &gt; 0.99) across lymphoid and myeloid subsets. iSort also showed high reproducibility among triplicate blood tubes for each population (median CV = 11%). Conclusions: iSort digital cytometry achieves highly accurate and robust leukocyte enumeration for diverse hematopoietic subsets. Given its favorable performance against existing clinical standards that require intact/living cells, iSort is a promising approach for the development of immunotherapy biomarkers.
Call for evidence-based medication
Authors: 刘岚, 姜民慧, 朱丽琳
Journal: BMJ (2007)

在疾病的各种临床治疗方法中,药物治疗是最基础、最普遍、最方便的.有资料显示,全球的患者有1/3是死于不合理用药,而不是疾病本身.近年来,许多疾病的药物治疗发生了巨大的变化,新药的研发及临床应用层出不穷,尤其是相关药物的大规模、多中心、随机对照的临床试验(RCT)结果相继问世,使得相关疾病的药物治疗指南不断更新。
Efficacy and safety of nivolumab for malignant mesothelioma in the real world.
Authors: Koji Mikami, Takashi Yokoi, Ryo Takahashi, Eisuke Shibata, Maiko Niki, Yasuhiro Nakajima, Yoshiki Negi, Hirotoshi Ishigaki, Akio Tada, Tomoki Higashiyama, Takao Kamei, Toshiyuki Minami, Kozo Kuribayashi, Takashi Kijima
Journal: Journal of Clinical Oncology (2020)

9052 Background: Until recently, the standard treatment for advanced malignant pleural mesothelioma (MPM) was only cisplatin plus pemetrexed. Nivolumab, an anti-programmed death-1 monoclonal antibody, shows efficacy against pretreated MPM and has been approved in Japan, but the data regarding the efficacy and safety of nivolumab in MPM are limited to those from a small number of patients of the MERIT study. Therefore, it is important to accumulate real-world data on the efficacy and safety of nivolumab for MPM. Methods: We retrospectively analyzed all patients with MPM who received nivolumab at Hyogo College of Medicine Hospital from August 2018 to December 2018. Results: A total of 77 patients (61 males and 16 females) were included. There were 62, 10, and 5 patients with performance statuses of 0–1, 2, and 3, respectively. There were 63, 8, and 6 patients with epithelioid, sarcomatoid, and bi-phasic histologies, respectively. Nivolumab was administered as second-, third-, and ≥fourth-line treatment to 48, 15, and 11 patients, respectively. In 66 patients who were examined for efficacy, the response rate (RR) was 24.2% and the disease control rate (DCR) was 63.6%. By the histology type, the RR and DCR were 15.1% and 62.3% for the epithelioid type, 62.5% and 87.5% for the sarcomatoid type, and 20.0% and 40.0% for the bi-phasic type, respectively. The median progression-free survival (mPFS) was 4.1 months and the median overall survival (mOS) was 13.3 months. Analyzing the efficacy based on the neutrophil-to-lymphocyte ratio (NLR) in the peripheral blood, the RRswere 14.7% in the NLR≥3.5 group and 25.8% in the NLR &lt; 3.5 group. The mPFS and mOS in the NLR≥3.5 group were 3.1 months and 11.4 months, respectively,whereas those in the NLR &lt; 3.5 group were 5.6 months and not reached, respectively. There were no significant differences in the RR, PFS, and OS between the groups, but a trend of better RRs and longer survivals wasobserved in the NLR &lt; 3.5 group than in the NLR≥3.5 group. Regarding adverse events, fatigue (grades 1−2) was observed in 8, hypothyroidism (grade 1–2) in 11, renal dysfunction (grade 1–3) in 6, loss of appetite (grade 1–2) in 2, pneumonitis (grade 3) in 1, rash (grade 1) in 2, and hypopituitarism (grade 3) in 1 patient(s). Conclusions: This retrospective study revealed the effectiveness and safety of nivolumab for MPM in the real-world setting.Nivolumab can be used as a standard second-line treatment for MPM. Furthermore, it has been suggested that the NLR may be a predictive marker of the effect of nivolumab for MPM, as pointed out in other carcinomas.
AcceleRET Lung: A phase III study of first-line pralsetinib in patients (pts) with RET-fusion+ advanced/metastatic non-small cell lung cancer (NSCLC).
Authors: Benjamin Besse, Enriqueta Felip, Corinne Clifford, Melinda Louie-Gao, Jennifer Green, Christopher D. Turner, Sanjay Popat
Journal: Journal of Clinical Oncology (2020)

TPS9633 Background: RET gene fusions have been identified as oncogenic drivers in multiple tumor types, including 1-2% of NSCLC, but no selective RET inhibitors are approved for use. The investigational RET inhibitor, pralsetinib, potently and selectively targets oncogenic RET alterations, including those that confer resistance to multikinase inhibitors. In the registration-enabling phase 1/2 study (ARROW; NCT03037385), pts with RET-fusion+ NSCLC treated with 400 mg once daily (QD) of pralsetinib (N = 80) after platinum-based chemotherapy achieved an overall response rate (ORR) of 61% (95% CI 50, 72; 2 responses pending confirmation) per independent central review. In addition, a promising ORR of 73% (all centrally confirmed responses) was attained in the treatment naïve cohort (N = 26). Most treatment-related adverse events were grade 1-2 across the entire safety population treated at 400 mg QD (N = 354). AcceleRET Lung, an international, open-label, randomized, phase 3 study, will evaluate the efficacy and safety of pralsetinib versus standard of care (SOC) for first-line treatment of advanced/metastatic RET fusion+ NSCLC (NCT04222972). Methods: Approximately 250 pts with metastatic RET-fusion+ NSCLC will be randomized 1:1 to oral pralsetinib (400 mg QD) or SOC (non-squamous histology: platinum/pemetrexed ± pembrolizumab followed by maintenance pemetrexed ± pembrolizumab; squamous histology: platinum/gemcitabine). Stratification factors include intended use of pembrolizumab, history of brain metastases, and ECOG PS. Key eligibility criteria include no prior systemic treatment for metastatic disease; RET-fusion+ tumor by local or central assessment; no additional actionable oncogenic drivers; no prior selective RET inhibitor; measurable disease per RECIST v1.1. Pts randomized to SOC will be permitted to cross-over to receive pralsetinib upon disease progression. The primary endpoint is progression-free survival (blinded independent central review; RECIST v1.1). Secondary endpoints include ORR, overall survival, duration of response, disease control rate, clinical benefit rate, time to intracranial progression, intracranial ORR, safety/tolerability and quality of life evaluations. Recruitment has begun with sites (active or planned) in North America, Europe and Asia. Clinical trial information: NCT04222972 .
一位神经纤维瘤病病人的上腹痛
Authors: 周仲华
Journal: BMJ (2006)

最近我看了一个病人,18岁,是个高中男孩.这孩子性格憨厚,在学习方面虽然努力,但很吃力,成绩也不理想.出生时,他父母就发现他的躯干和大腿上有几个淡棕色、表面光滑、边界清楚、直径约10 mm的色斑,随着年龄的增长而略长大,但没有不适症状,也未治疗过.5年前他的躯干部和四肢皮肤出现了很多包块,呈肉色,大小不等,直径约0.5～2.0 cm,边界清楚,质地中等,不痛也不痒。
以神经系统症状为首发表现的血栓性血小板减少性紫癜九例
Authors: 李辉华, 丁江华, 张荣艳
Journal: BMJ (2004)

对9例以神经系统症状为首发表现的血栓性血小板减少性紫癜(TTP)患者的临床资料进行总结,显示该病女性较多,起病急且易反复发作,临床表现为微血管血栓所致的多系统损害,初诊时并非同时出现五联征,多变性神经症状可为首发症状,脑CT提示TTP可并发缺血和出血性脑血管损害。
Yap1-Scribble polarization is required for hematopoietic stem cell division and fate
Authors: Mark J. Althoff, Ramesh C. Nayak, Shailaja Hegde, Ashley M. Wellendorf, Breanna Bohan, Marie-Dominique Filippi, Mei Xin, Q. Richard Lu, Hartmut Geiger, Yi Zheng, Maria T. Diaz-Meco, Jorge Moscat, Jose A. Cancelas
Journal: Blood (2020)
Analyses of serum free fatty acid composition and other glucose and lipid metabolic parameters in middle and old-aged patients with metabolic syndrome in community
Authors: 李嘉强, 李妙英, 刘玉敏, 戴颖秀, 郑基, 刘文斌
Journal: BMJ (2007)

目的 探讨社区中代谢综合征(MS)患者血清游离脂肪酸谱特征及与其他糖脂代谢参数间关系.方法 采用国际糖尿病联盟MS的诊断标准,用气相色谱-质谱方法测定社区居民中158例含MS不同组分患者[MS患者61例(MS组),MS高危者97例(MS高危组)]与43例体检正常者(对照组)血清游离脂肪酸组分.结果 MS组多不饱和脂肪酸、n6系多不饱和脂肪酸浓度等高于MS高危与对照组(P＜0.01或P＜0.05).MS组中有糖尿病与无糖尿病者相比,血清游离脂肪酸各组分浓度差异均无统计学意义(P＞0.05).MS高危组中,有糖尿病者亚油酸、n6系多不饱和脂肪酸、总游离脂肪酸(TFA)浓度等高于无糖尿病者,饱和脂肪酸/总脂肪酸值低于无糖尿病者(P＜0.05或P＜0.01).3组单不饱和脂肪酸/总脂肪酸值的均值为0.15左右.TFA、多不饱和脂肪酸与体重指数、平均血压、空腹血糖、甘油三酯呈正相关(r=0.164和0.211,0.217和0.287,0.198和0.275,0.266和0.158,P＜0.05或P＜0.01).结论 游离脂肪酸与MS多种组分相关.TFA、n6系多不饱和脂肪酸升高,单不饱和脂肪酸缺乏,可能在其发病中起重要作用。
Cost-effectiveness of neoadjuvant FOLFIRINOX versus gemcitabine plus nab-paclitaxel in locally advanced/borderline resectable pancreatic cancer patients.
Authors: Myles Ingram, Brianna N Lauren, Yoanna S Pumpalova, Gulam Abbas Manji, Susan Elaine Bates, Chin Hur
Journal: Journal of Clinical Oncology (2020)

e16793 Background: The 2019 NCCN guidelines recommend neoadjuvant FOLFIRINOX or neoadjuvant gemcitabine plus nab-paclitaxel (G-nP) for locally advanced and borderline resectable pancreatic ductal adenocarcinoma (BR/LA PDAC). Neoadjuvant FOLFIRINOX and G-nP have yet to be directly compared in a prospective, randomized trial with BR/LA PDAC patients. The purpose of our study was to incorporate treatment outcomes, toxicity profiles, costs, and quality-of-life measures to further inform clinical decision-making. Methods: We developed a decision-analytic mathematical model to compare the total cost and health outcomes of neoadjuvant FOLFIRINOX against G-nP over twelve years. Adjuvant gemcitabine (GEM) was used as a comparator. The inputs for the model were estimated using clinical trial data and published literature. We used single-institution retrospective studies to estimate our survival data in the absence of a prospective trial. The primary endpoint was incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted-life-year (QALY). Secondary endpoints included overall (OS) and progression-free survival (PFS), total cost of care (USD), QALYs, patient resection rate, and monthly treatment-related adverse events (TRAE) costs (USD). Results: FOLFIRINOX was the cost-effective strategy, totaling incremental QALYs of 0.21 at a cost of $52,845.96 per QALY when compared to G-nP. G-nP was also on the efficiency frontier with an ICER of $46,430.73 compared to GEM. More patients received resection with FOLFIRINOX (82.15% vs. 72.40%), but had higher TRAE costs than G-nP ($12,051.26 vs. $4,666.97). A one-way sensitivity analysis found that the FOLFIRINOX ICER exceeds the WTP threshold when TRAE costs are higher and resection rates are lower. Conclusions: Our modeling analysis finds FOLFIRNOX is the cost-effective treatment compared to G-nP for BR/LA PDAC despite having a higher cost of total care due to TRAE costs. Trial data with sufficient follow-up are needed to confirm our findings. [Table: see text]
Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease
Authors: Smith Einar, Ottosson Filip, Hellstrand Sophie, Ericson Ulrika, Orho-Melander Marju, Fernandez Céline, Melander Olle, 冯博
Journal: BMJ (2020)

目的
近期研究发现一种健康饮食模式（HCFP）与降低心脏代谢疾病风险相关，但导致这种相关性的分子机制尚不明确。该研究旨在发现与这种饮食模式相关的血浆代谢物，并研究其与心脏代谢疾病发生和死亡风险的相关性。


方法
从全人群马尔默饮食和癌症研究中，筛选出3 236名无心血管疾病和糖尿病史的参与者。运用液相色谱-质谱法对他们的112种血浆代谢物进行检测。通过多元线性回归和Bonferroni校正分析，发现其中与该饮食模式相关的代谢物。使用多变量Cox比例风险模型进行长期随访分析后，发现这些健康饮食的生物标志物与心脏代谢疾病的发生和死亡风险相关。


结果
平均随访21.4年期间，603人患心血管疾病，362人患糖尿病，843人死亡。基线资料中，5种健康饮食标志物与该饮食模式相关（P<0.000 4），其中4种与至少一项研究终点相关（P<0.05）。麦角硫因是与该饮食模式相关性最强的代谢物，并且与降低冠心病风险（危害比0.85，P=0.01）、心血管死亡风险（危害比0.79，P=0.002）、全因死亡风险（麦角硫因每增加一个标准差的危害比，危害比0.86，P=4e-5）相关。


结论
我们发现高麦角硫因含量是降低心脏代谢疾病发生和死亡风险的独立标志物。而这种高含量很可能是由某种特殊的饮食方式造成的。
Oncologic outcomes of complete transurethral resection prior to neoadjuvant chemotherapy for muscle-invasive bladder cancer.
Authors: Jamie Sungmin Pak, Christopher R Haas, Helena Vila Reyes, Christopher B. Anderson, Guarionex Joel DeCastro, Mitchell C. Benson, James M. McKiernan
Journal: Journal of Clinical Oncology (2020)

e17029 Background: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) is the standard of care for muscle-invasive bladder cancer (MIBC). Prior studies have shown that pT0 response at RC can be attributed to NAC and high-quality transurethral resections (TURBT) prior to NAC. Therefore, we sought to assess the association of completeness of pre-NAC TURBT with response and survival outcomes. Methods: This was a single-institution, retrospective review of patients who received NAC for clinically localized MIBC (≥cT2, N0) from 2000 to 2017. Exclusion criteria were receipt of non-cisplatin-based NAC or radiation (n = 15), and insufficient documentation of TURBT (n = 26). Complete TURBT (cTURBT) was defined as tumor resection in entirety and/or resection to normal appearing muscle in operative reports, or repeat pre-NAC TURBT revealing clinical T0 (cT0). After NAC, patients either underwent repeat TURBT or immediate RC, as per the treating physician. Patients refusing RC were placed on an active surveillance/delayed intervention (ASDI) protocol of cytology, cystoscopy, and imaging at 3-4 month intervals. Primary endpoint was durable complete response (dCR): pT0 at RC or remaining cT0 on ASDI for ≥1 year. Secondary endpoints included OS and durable down-staging (dDS): ≤pT1 at RC or remaining ≤cT1 on ASDI for ≥1 year. Results: Of a total 93 patients, 62 (67%) underwent pre-NAC cTURBT. Those with cTURBT had lower rates of variant histology (13% vs 32%, p = 0.03), hydronephrosis (15% vs 39%, p &lt; 0.01), and more often pursued ASDI (60% vs 26%, p = 0.01). Patients with cTURBT were more likely to attain dCR (37% vs 13%, p = 0.01) and dDS (60% vs. 26%, p &lt; 0.01). On multivariate (MV) analysis, cTURBT was a significant predictor of dCR and dDS; this remained true on subset analysis excluding 11 patients with ≥cT3 on restaging TURBT. On Kaplan-Meier analysis, patients with cTURBT had improved 5-year OS (78% vs. 46%, p &lt; 0.01). On MV analysis controlling for variant histology, lymphovascular invasion, and hydronephrosis, cTURBT was the only significant predictor of OS, also on subset analysis excluding the 11 patients with ≥cT3 on restaging TURBT. Conclusions: A pre-NAC cTURBT is associated with improved oncologic outcomes and OS in this MIBC cohort. The extent to which cTURBT represents a selection criterion for having lower clinical stage or a therapeutic advantage in response to NAC is difficult to isolate from a retrospective study. However, this study suggests cTURBT should be pursued when feasible to potentially optimize outcomes after NAC.
Assessing the significance of KRAS G12C mutation: Clinicopathologic features, treatments, and survival outcomes in a real-world KRAS mutant non-small cell lung cancer cohort.
Authors: Wanyuan Cui, Fanny Franchini, Marliese Alexander, Ann Officer, Hui Li Wong, Maarten J. IJzerman, Jayesh Desai, Benjamin J. Solomon
Journal: Journal of Clinical Oncology (2020)

e19324 Background: KRAS G12C mutations are present in 15% of non-small cell lung cancer (NSCLC) and have recently been shown to confer sensitivity to KRAS(G12C) inhibitors. This study aims to assess the clinical features and outcomes with KRAS G12C mutant NSCLC in a real-world setting. Methods: Patients enrolled in an Australian prospective cohort study, Thoracic Malignancies Cohort (TMC), between July 2012 to October 2019 with metastatic or recurrent non-squamous NSCLC, with available KRAS test results, and without EGFR, ALK, or ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival was compared for KRAS wildtype ( KRAS WT ) and KRAS mutated ( KRAS mut ) patients, and between KRAS G12C ( KRAS G12C ) and other ( KRAS other ) mutations. Results: Of 1386 patients with non squamous NSCLC, 1040 were excluded for: non metastatic or recurrent (526); KRAS not tested (356); ALK, EGFR or ROS1 positive (154); duplicate (4). Of 346 patients analysed, 202 (58%) were KRAS WT and 144 (42%) were KRAS mut , of whom 65 (45%) were KRAS G12C . 100% of pts with KRAS G12C were smokers, compared to 92% of KRAS other and 83% of KRAS WT . The prevalence of brain metastases over entire follow-up period was similar between KRAS mut and KRAS WT (33% vs 40%, p = 0.17), and KRAS G12C and KRAS other (40% vs 41%, p = 0.74). Likewise, there was no difference in the proportion of patients receiving one or multiple lines of systemic therapy. Overall survival (OS) was also similar between KRAS mut and KRAS WT (p = 0.54), and KRAS G12C and KRAS other (p = 0.39). Conclusions: In this real-world prospective cohort, patients had comparable clinical features regardless of having a KRAS mut , KRAS G12C or KRAS other mutation, or being KRAS WT . Treatment and survival were also similar between groups. While not prognostic, KRAS G12C may be an important predictive biomarker as promising KRAS G12C covalent inhibitors continue to be developed.