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Survival data support the use of first-line osimertinib as the standard of care for epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC). However, it remains unclear whether upfront osimertinib is superior to sequential first- or second-generation tyrosine kinase inhibitors (TKIs) followed by osimertinib for all patients. It is impossible to predict which patients are at high risk of progression, and this constitutes a major limitation of the sequential TKI approach.A total of 830 plasma samples from 228 patients with stage IV, EGFR-positive NSCLC who were treated with first-line TKIs were analysed by digital polymerase chain reaction (dPCR).The circulating tumour DNA (ctDNA) levels helped to identify patients with significantly improved survival rate, regardless of the treatment. Patients treated with first- or second-generation TKIs (N = 189) with EGFR mutations in plasma at a mutant allele frequency (MAF)7% before treatment initiation (low-risk patients) or who were ctDNA negative after 3 or 6 months of treatment and with an MAF7% at diagnosis (high responders) had two-thirds lower risk of death than patients in the opposite situation (adjusted hazard ratio [HR] = 0.38; 95% confidence interval [CI]: 0.23-0.64 and HR = 0.22; 95% CI: 0.12-0.42, respectively). The median overall survival (OS) for low-risk patients and high responders treated with first- or second-generation TKIs was 34.2 months and not reached, respectively, regardless of second-line treatment. There were no significant difference in OS between low-risk or high-responder patients treated upfront with osimertinib (N = 39) and those treated under a sequential approach with osimertinib (N = 60). Median OS was not reached in both cases.Pre-treatment ctDNA levels identify low-risk patients, who may benefit from sequential TKI treatment. Information regarding EGFR mutation clearance can help to improve patient selection.

Introduction: There are currently no predictive biomarkers for long-term survival after neoadjuvant chemoimmunotherapy. However, the identification of non-small lung cancer (NSCLC) patients who obtain long-term benefit from chemoimmunotherapy is essential to optimize therapies. Methods: Using samples from NADIM clinical trial (NCT03081689), in which resectable stage IIIA NSCLC patients were treated with neoadjuvant chemo-immunotherapy with nivolumab, we have evaluated the capacity of ctDNA levels before treatment initiation to predict overall survival (OS) and progression-free survival (PFS) by calculating Harrell’s C-statistic and we compare its predictive value with classical survival surrogates as the pathological response and clinical response assessed according to RECIST criteria v.1.1. The ctDNA was analyzed by NGS, using the Oncomine Pan-Cancer Cell-Free Assay™ (Thermo Fisher Scientific®). To explore the prognostic value of the amount of ctDNA at baseline, for each positive plasma sample, we calculated the sum of the mutant allele frequency (MAF) for all detected mutations. Patients who died from COVID19 were excluded from this analysis. Results: In our study, clinical responses based on RECIST criteria were not predictive for OS or PFS. On the contrary, in the multivariate analysis, patients with low ctDNA levels (

Background: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored. Materials and methods: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR. Results: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRASG12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRASG12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRASG12C patients tested negative for the presence of p.T790M resistance mutation. Conclusions: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRASG12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical feature, This work was supported by CLARIFY project (https://www.clarify2020.eu/). ES-H was supported by the Consejería de Ciencia, Universidades e Innovación of the Comunidad de Madrid (Doctorados Industriales of the Comunidad de Madrid) [grant number IND2019/BMD-17258]. EG-V was supported by AECC (Asociación española Contra el Cáncer) grant ‘Programa de Prácticas de Laboratorio de curso académico AECC 2020’ (no grant number).

Background: Madrid has been the epicenter of the SARS-CoV2 pandemic in Spain. We analyzed the experience at our hospital with SARS-CoV2 infection and cancer patients (p). Method(s): We analyzed our experience from March 1 to April 30 at the Puerta de Hierro University Hospital in Madrid. Diagnosis of SARS-CoV2 infection was made by RT-PCR, suspected cases not confirmed were excluded. Result(s): Overall in-hospital mortality cancer p with COVID-19 was 15.2% (95%CI, 6.3;5.2), similar to 12.7% (95%CI,11.1;4.4) with p=0.615 of the global COVID-19 hospitalised population and greater than that of patients admitted without SARS-CoV-2 infection during the same period 4.3% (95%CI;3.6;5.2) p0.001. Among 653 patients receiving active cancer therapy during this period, 24 (3.7%) developed COVID-19 and required admission, 4.2% of were receiving chemotherapy, 9.5% immunotherapy and 2.1% targeted therapies. Lung and breast cancer were the most frequent (26.1%), followed by colorectal (19.6%) and breast cancer. No significant differences due to the cancer treatment received were observed. Mortality in lung cancer patients was the highest (25%). The univariate analysis (between p who developed serious event vs. those who did not), showed that higher Brescia, CURB-65 scale, lactate dehydrogenase (LDH) or C-reactive protein (CRP) levels at admission, the greater risk of developing severe complications (p0.05) [Formula presented]. Conclusion(s): Patients with cancer, especially lung cancer, and SARS-CoV2 infection have a worse overall prognosis than the general population. Objective parameters such as LDH, CRP at admission, Brescia index or CURB-65 should alert us to a more serious evolution and suggest early an early intensive care unit (ICU) admission. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2020

Background: Liquid biopsy has evolved from being a promising line to becoming a validated approach for biomarker testing. However, its utility for individualization of therapy has been scarcely reported. In this study, we show how monitoring levels of EGFR mutation in plasma can be useful for the individualization of treatment. Results: Longitudinal EGFR mutation levels in plasma always correlated with tumor response ascertained by RECIST criteria. Moreover, decreasing EGFR mutation levels were detected in all patients benefiting from locoregional radiotherapy, whereas the opposite occurred when a patient progressed soon after radiotherapy treatment. Similarly, increasing EGFR mutation levels anticipated disease progression after TKI dose reduction, discontinuation of treatment, or reduced bioavailability due to drug interactions. In addition, EGFR mutation levels were useful to monitor treatment outcome of new therapies and constituted a decisive factor when the clinical situation of the patient did not correlate with responses ascertained by radiologist. Finally, our results indicate that cancer associated body fluids (pleural, pericardial or cerebrospinal fluid) are certainly a suitable source for biomarker testing that can extend EGFR mutation detection to biofluids other than blood. Materials and Methods: A total of 180 serial plasma samples from 18 non-smallcell lung cancer patients who carried an activating EGFR mutation were investigated by digital PCR. Conclusions: Monitoring levels of EGFR mutation in plasma allows resolving doubts that frequently arise in daily clinical practice and constitutes a major step towards achieving personalized medicine, This study was supported by Carlos III Institute of Health, Spanish Ministry of Science and Innovation, and European Regional Development Fund (grant number: PI16/01818 and PIE14/00064), A Romero is supported by Joan Rodés fellowship (grant number: JR14/00017) and CP pre-doctoral studies are supported by Jose Luís Castaño Foundation

Background PET/CT is an essential component in the initial assessment of locally advanced NSCLC. However, the role of PET/CT in the assessment of response to therapies is not well established. Methods We reviewed all stage III NSCLC patients assessed at our centre between January 2009 and March 2018, selecting those with PET/CT evaluation at diagnosis and after treatment (chemotherapy and/or radiotherapy). We evaluated the prognostic differences between mayor PET/CT response (reduction of ≥ 50% of initial SUVmax), minor PET response (reduction of Results We reviewed 249 patients. In 92,3% an initial PET/CT evaluation was carried out. 117 patients (46.9%) had a PET/CT re-evaluation after an initial chemotherapy and/or radiotherapy treatment. We observed a higher risk of disease progression in patients with a minor PET/CT response (HR 1.97; IC95% 1.2-3.2) and without a response (HR 2.3; IC95% 1.4-4.6, p 2.5 presented a sensitivity of only 42.9% and a specificity of 87.5%. Conclusions PET/CT response after induction therapy was a good prognosticator for PFS and OS in stage III NSCLC patients. However, response evaluation by PET/CT should be interpreted with caution due to its lack of precision. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure V. Calvo de Juan: Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self): Boerhinger; Honoraria (self): Roche. M. Provencio: Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Boerhinger. All other authors have declared no conflicts of interest.

Objective TO assess the prognostic value of a series of clinicopathological variables in stage I nonsmall cell lung cancer, for tumors up to 3 cm in diameter. Patients and method The study included 271 patients. Survival was analyzed with the Kaplan-Meier method. The Cox model was used for multivariate analysis. Results Five- and ten-year survival were 78.63% and 67.59%, respectively. Survival did not significantly depend on sex, age, extent of resection, histology, visceral pleural invasion, level of bronchial invasion or T1 versus T2. The decade in which resection was performed did affect survival ( P =.0037). Five-year survival was 58% for operations between 1970 and 1980, 77% for operations between 1981 and 1990, and 84% for operations between 1991 and 2000. Tumor size also affected survival ( P =.0046), which was 86% for patients with tumors of less than or equal to 2 cm in diameter and 73% for those with tumors of more than 2 cm in diameter. In the multivariate analysis both variables entered into regression, remaining predictive of survival. Conclusion We found evidence for a prognostic stage migration (Will Rogers phenomenon) according to the decade in which resection was performed and that tumor size affected survival in our population. Finally, the current system of TNM staging fails in conforming groups of patients with a homogenous prognosis.

Background: The aim of this work is to estimate the prognostic value of a set of clinical–pathological factors in patients resected for non-small cell lung cancer (NSCLC) and classified as stage IB, in order to create a prognostic model for establishing risk groups, and to validate that model. Methods: Among 637 patients resected and classified as stage IB, we analyzed sex, age, symptoms, location, type of resection, cell type, histology, and tumor size. The Kaplan–Meier method was used to estimate the survival. The results were compared using the log-rank test. All the significant variables from this univariable method were then included in a multivariable method of estimation of the proportional risk for survival data developed by Cox, using the variables selected, a regression model was developed for accurately predicting survival. To validate the predictive capability of the regression model, we randomly divided our patients into training and test subsets, containing 322 and 315 cases, respectively. Results: The overall 5-year survival rate of the series was 60%. The cell type, the squamous or non-squamous and the tumor size showed a significant influence on survival in the univariable analysis, while, according to the Cox model, only the tumor size and the squamous or non-squamous type entered into regression. Hazard rates were calculated for each patient. The mean risk was 0.87±0.25 (range 30–1.94). The series was divided into three risk groups (low, intermediate, and high risk) according to the fitted hazard rates, using cut-off points (one standard deviation from the mean). The 5-year survival rates were 85, 59, and 44%, respectively. To validate the model, we repeated the analysis for training and test subsets. Only the tumor size had a significant influence on survival in the univariable analysis. Using the Cox model, also the tumor size entered into regression. The mean risk was 0.79±0.29 (range 0.09–2.12). Cut-off points were 0.50 and 1.08 for the low, intermediate, and high-risk groups. The 5-year survival rates were 83, 58, and 40%, respectively. We validated the regression model obtained in the training subset by demonstrating its capacity in identifying risk groups in the test subset. The 5-year survival rates were 83, 61, and 49.5% for the low, intermediate, and high-risk groups, respectively ( P =0.0104). Conclusions: Stage IB does not succeed in configuring a group of patients with a homogeneous prognosis, as there is a wide variability in a 5-year survival. The estimation of prognosis derived from a multivariable analysis can obviate the limitations of the actual staging system for NSCLC.