Despite TNM (Tumour, Node, Metastasis) classification being the gold standard for estimating the prognosis of early-stage colorectal cancer, significant variability in long-term survival persists among patients within the same TNM stage, underscoring the importance of the disease's biological heterogeneity and the need for novel markers. This study investigates the determinants of 5-year mortality in patients with colon or rectal cancer through the analysis of 448 diagnostic tumour samples from a prospective multicentre cohort. We assessed sociodemographic, clinical, and pathological data, as well as the apoptotic index (AI) measured by the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) technique. Overall survival was the primary outcome, and Cox regression was used to estimate the hazard ratio (HR). Multivariate 5-year survival analysis identified the highest risk associated with TNM stages IV [p<0.001, HR 12.06, confidence interval (CI) 5.75-25.31] and III (p<0.001, HR 3.52, CI 1.88-6.62), followed by an AI >1.8% (p<0.001, HR 2.16, CI 1.46-3.20), male biological sex (p<0.05, HR 1.58, CI 1.05-2.37), tumour location on the right colon (p<0.024, HR 1.55, CI 1.06-2.27), and age (p<0.001, HR 1.05, CI 1.04-1.07). Our findings underscore the long-term prognostic value of a high AI as a determinant of poor prognosis in colorectal cancer and highlight the need to refine conventional prognostic markers to enable more precise risk stratification.

BackgroundColorectal cancer (CRC) continues to be a major health concern in today’s world. Despite conflictive findings, evidence supports systemic inflammation’s impact on CRC patients’ survival rates. Therefore, this study aims to assess the prognostic role of the innate immune system in patients with CRC.MethodA total of 449 patients were included, with a 5-year follow-up period, and absolute neutrophil counts and their related ratios were measured.ResultsThe non-survival group had increased levels of white blood cells, neutrophils (both p<0.001), and monocytes (p=0.038), compared to the survival group, along with other neutrophil-related ratios. We observed increased mortality risk in patients in the highest tertile of white blood cells [HR=1.85 (1.09-3.13), p<0.05], neutrophils [HR=1.78 (95% CI: 1.07-2.96), p<0.05], and monocytes [HR=2.11 (95% CI: 1.22-3.63)], compared to the lowest tertile, after adjusting for all clinicopathological variables. Random forest analysis identified neutrophils as the most crucial variable in predicting survival rates, having an AUC of 0.712, considering all clinicopathological variables. A positive relationship between neutrophil counts and metastasis was observed when neutrophil counts are considered continuous (β=0.92 (0.41), p<0.05) and tumor size (width) when neutrophils were considered as logistic variable (T1 vs T3) [OR=1.42, (95% CI: 1.05-1.98), p<0.05].ConclusionThis study offers comprehensive insights into the immune factors that impact the prognosis of CRC, emphasizing the need for personalized prognostic tools.

Colorectal cancer (CRC) has a 5-year overall survival rate of over 60%. The decrease in the rate of metastatic disease is due to screening programs and the population's awareness of healthy lifestyle. Similarly, advancements in surgical methods and the use of adjuvant chemotherapy have contributed to a decrease in the recurrence of resected disease. Before evaluating a patient's treatment, it is recommended to be discussed in a multidisciplinary tumor board. In stage II tumors, the pathologic characteristics of poor prognosis must be known (T4, number of lymph nodes analyzed less than 12, lymphovascular or perineural invasion, obstruction or perforation, poor histologic grade, presence of tumor budding) and it is mandatory to determine the MSI/MMR status for avoiding administering fluoropyridimidines in monotherapy to patients with MSI-H/dMMR tumors. In stage III tumors, the standard treatment consists of a combination of fluoropyrimidine (oral or intravenous) with oxaliplatin for 6 months although the administration of CAPOX can be considered for 3 months in low-risk tumors. Neoadjuvant treatment is not consolidated yet although immunotherapy is achieving very good preliminary results in MSI-H patients. The use of ctDNA to define the treatment and monitoring of resected tumors is only recommended within studies. These guidelines are intended to help decision-making to offer the best management of patients with non-metastatic colon cancer.

Introduction: The mitogen-activated protein kinase (MAPK) signalling network aberrations in metastatic colorectal cancer (mCRC) generate intrinsic dynamic effects and temporal variations that are crucial but often overlooked in clinical trial populations. Here, we investigate the time-varying impact of MAPK pathway mutation genotype on each treatment line's contribution to the overall clinical course.Methods: The PROMETEO study focused on mCRC patients undergoing second-line treatment at 20 hospitals. We evaluated genotypes and employed flexible models to analyse the dynamic effect of each mutation.Results: We examined data derived from 1160 patients. The effects of KRAS G12C or G12V, and BRAF V600E are clearly time-varying, with unexpected consequences such as the deleterious effect of BRAF V600E vs other genotypes dissipating over time when subjects receive antiangiogenics, or KRAS G12V and G12C showing increasing aggressiveness over time. Thus, contrary to expectations, the 12-month survival rate from the second line for those who survived >6 months was 49.9% (95% CI, 32.7-67.3) for KRAS G12C and 59% (95% CI, 38.5-80.6) for BRAF V600E.Conclusions: The dynamic perspective is essential for understanding the behaviour of tumours with specific genotypes, especially from the second line onward. This may be relevant in patient monitoring and treatment decision-making, particularly in cases with distinct mutations.

Introduction: The initial SARS-CoV-2 pandemic wave in Spain in 2020 precipitated significant paradigm shifts in gastrointestinal oncology patient management. This study captures the "Zeitgeist" of this period by analyzing adaptive strategies, treatment modifications, and survival outcomes, leveraging a 3-year follow-up perspective to extract insights from this unprecedented experience. Methods: We conducted a multicenter, retrospective cohort study utilizing the RETUD-TTD registry, encompassing 703 patients across 19 Spanish centers in April 2020. We evaluated alterations in clinical practice, therapeutic approaches, coronavirus disease 2019 (COVID-19)-related impacts, and patient survival. A Bayesian hierarchical model was employed to identify potential regional-specific frailties. Results: The peak of the pandemic in April 2020 catalyzed substantial shifts in oncological care delivery. Outpatient consultations decreased by 13%, with a notable selection bias toward cases with more favorable prognostic indicators. Multidisciplinary tumor board discussions were significantly curtailed (eg, mean monthly colorectal cancer cases discussed was reduced from 40 to 23), compromising qualitative care measures. This occurred concurrently with an average of over 3 oncologists per center on medical leave. Contrary to initial concerns, the healthcare system demonstrated remarkable resilience. The majority of patients received standard-of-care therapies with regulatory approval, albeit with regimen modifications in 15% of cases. These adaptations included extended dosing intervals, dose intensity modulations, and transitions to oral formulations while maintaining unexpectedly stable long-term survival outcomes. The Bayesian frailty model detected minimal unmeasured prognostic factors related to geographic location, and the type of pandemic-induced adaptation did not significantly impact survival. The model revealed that coronavirus disease 2019's impact was less pronounced than other core prognostic variables. Conclusions: The decentralized Spanish healthcare system exhibited substantial robustness in managing pre-pandemic diagnosed gastrointestinal malignancies, despite asymmetrical, and occasionally severe organizational disruptions. The insights gleaned from this experience could inform future crisis preparedness strategies and optimize care provision during subsequent public health emergencies.

DNA damage has been extensively studied as a potentially helpful tool in assessing and preventing cancer, having been widely associated with the deregulation of DNA damage repair (DDR) genes and with an increased risk of cancer. Adipose tissue and tumoral cells engage in a reciprocal interaction to establish an inflammatory microenvironment that enhances cancer growth by modifying epigenetic and gene expression patterns. Here, we hypothesize that 8-oxoguanine DNA glycosylase 1 (OGG1)-a DNA repair enzyme-may represent an attractive target that connects colorectal cancer (CRC) and obesity. In order to understand the mechanisms underlying the development of CRC and obesity, the expression and methylation of DDR genes were analyzed in visceral adipose tissue from CRC and healthy participants. Gene expression analysis revealed an upregulation of OGG1 expression in CRC participants (p < 0.005) and a downregulation of OGG1 in normal-weight healthy patients (p < 0.05). Interestingly, the methylation analysis showed the hypermethylation of OGG1 in CRC patients (p < 0.05). Moreover, expression patterns of OGG1 were found to be regulated by vitamin D and inflammatory genes. In general, our results showed evidence that OGG1 can regulate CRC risk through obesity and may act as a biomarker for CRC.

3597 Background: There are no randomized trials comparing the addition monoclonal antibodies (MAB: bevacizumab, cetuximab, panitumumab) to first line chemotherapy (upfront use) versus deferring their addition to the second-line chemotherapy (deferred use) in pts with metastatic colorectal cancer (mCRC). We emulated a target trial comparing upfront vs deferred use of MAB using the GEMCAD 14-01 observational registry. Methods: We first specified the (hypothetical) target trial to fully articulate the research question and then emulated it using real-world data. The eligibility criteria of the target trial were a diagnosis of mCRC, being treatment naïve, and a ECOG PS <2. The target trial would randomize pts to the following strategies: (1) initiation of MAB within 2 months of starting first line chemotherapy (“upfront MAB”) and (2) initiation of MAB within 2 months of starting second line chemotherapy (“deferred MAB”). The primary outcome of the target trial would be overall survival and the causal contrast (or estimand) would be the effect under complete adherence. We emulated this target trial using data from the GEMCAD 1401 registry (ClinicalTrials.gov identifier: NCT02254941), which collected data prospectively from 47 Spanish centers from June 2014 to June 2018. The emulation used the same definitions of eligibility criteria and treatment strategies, and classified individuals according to their baseline data using clones. The effect under complete adherence was estimated by censoring pts when they deviated from the assigned treatment strategy and by using time-varying weights to adjust for baseline and post-baseline confounding. Results: A total of 627 pts were eligible in the ‘’upfront MAB’’ and 397 pts in the ‘’deferred MAB’’. Median age was in the ‘’upfront vs deferred’’ 64.6 (interquartile range: 56-71) vs 67.8 (61-75) years, 96% vs 87% had an ECOG 0-1, 80% vs 79% had a Charlson score < 3, 46% vs 60% had a RAS mutation, 6% vs 4% had a BRAF mutation, 72% vs 69% had left side primary location, 74% in both strategies had liver metastasis and 42% vs 50% had LDH levels above the normal threshold. Pts in the “upfront MAB” group contributed a total 16,057 months of follow-up and 502 if them died. Pts in the “deferred MAB” contributed a total of 7,774 months of follow-up, and 222 of them died. The 48-month overall survival was 26.7% (95% CI 21.4-38.2%) in the “upfront MAB” group and 21.6% (14.2-41.7%) in the “deferred MAB” group, corresponding to a 48-month survival difference (“upfront MAB” is the reference) of -5.0% (95% CI -17.9 to 17.95) and a hazard ratio or 1.15 (0.88-1.40). Conclusions: Our study suggests little or no survival detrimental effect of deferring the use of MAB to the second line of treatment compared with the use of MAB as part of the first line of treatment among pts with mCRC. Clinical trial information: NCT02254941 .

Esophageal cancer is an aggressive tumor, and is the sixth-leading cause of death from cancer. Incidence is rising in Spain, particularly among men. Two main pathological different subtypes have been described: squamous cell carcinoma and adenocarcinoma. Growing evidence of their epidemiology and molecular differences explains their different response to novel treatments, and they are therefore likely to be treated as two separate entities in the near future. The best results are obtained with a multidisciplinary therapeutic strategy, and the introduction of immunotherapy is a promising new approach that will improve prognosis. In these guidelines, we review the evidence for the different methods of diagnosis and therapeutic strategies that form the basis of our standard of care.

Objective The prevalence of depressive symptoms immediately after the diagnosis of colorectal cancer (CRC) is high and has important implications both psychologically and on the course of the disease. The aim of this study is to analyse the association between depressive symptoms and CRC survival at 5 years after diagnosis. Methods This multicentre, prospective, observational cohort study was conducted on a sample of 2602 patients with CRC who completed the Hospital Anxiety and Depression Scale (HADS-D) at 5 years of follow-up. Survival was analysed using the Kaplan-Meier method and Cox regression models. Results According to our analysis, the prevalence of depressive symptoms after a CRC diagnosis was 23.8%. The Cox regression analysis identified depression as an independent risk factor for survival (HR = 1.47; 95% CI: 1.21-1.8), a finding which persisted after adjusting for sex (female: HR = 0.63; 95% CI: 0.51-0.76), age (>70 years: HR = 3.78; 95% CI: 1.94-7.36), need for help (yes: HR = 1.43; 95% CI: 1.17-1.74), provision of social assistance (yes: HR = 1.46; 95% CI: 1.16-1.82), tumour size (T3-T4: HR = 1.56; 95% CI: 1.22-1.99), nodule staging (N1-N2: HR = 2.46; 95% CI: 2.04-2.96), and diagnosis during a screening test (yes: HR = 0.71; 95% CI: 0.55-0.91). Conclusions There is a high prevalence of depressive symptoms in patients diagnosed with CRC. These symptoms were negatively associated with the survival rate independently of other clinical variables. Therefore, patients diagnosed with CRC should be screened for depressive symptoms to ensure appropriate treatment can be provided.

Colorectal cancer affects men and women alike. Sometimes, due to clinical-pathological factors, the absence of symptoms or the failure to conduct screening tests, its diagnosis may be delayed. However, it has not been conclusively shown that such a delay, especially when attributable to the health system, affects survival. The aim of the present study is to evaluate the overall survival rate of patients with a delayed diagnosis of colorectal cancer. This observational, prospective, multicenter study was conducted at 22 public hospitals located in nine Spanish provinces. For this analysis, 1688 patients with complete information in essential variables were included. The association between diagnostic delay and overall survival at five years, stratified according to tumor location, was estimated by the Kaplan–Meier method. Hazard ratios for this association were estimated using multivariable Cox regression models. The diagnostic delay ≥ 30 days was presented in 944 patients. The presence of a diagnostic delay of more than 30 days was not associated with a worse prognosis, contrary to a delay of less than 30 days (HR: 0.76, 0.64–0.90). In the multivariate analysis, a short delay maintained its predictive value (HR: 0.80, 0.66–0.98) regardless of age, BMI, Charlson index or TNM stage. A diagnostic delay of less than 30 days is an independent factor for short survival in patients with CRC. This association may arise because the clinical management of tumors with severe clinical characteristics and with a poorer prognosis are generally conducted more quickly.

3500 Background: In the phase III, randomized open-label KEYNOTE-177 (NCT02563002) study 1L pembrolizumab (pembro) versus chemotherapy (chemo) provided superior progression-free survival (PFS) at second interim analysis (IA2) in patients (pts) with MSI-H/dMMR mCRC. The study continued to final analysis of overall survival (OS), planned after 190 OS events or 12 months after IA2, whichever occurred first. We present results of the final analysis of OS, 12 months after IA2. Methods: A total of 307 pts with MSI-H/dMMR mCRC and ECOG PS 0 or 1 were randomized 1:1 to 1L pembro 200 mg Q3W for up to 2y or investigator’s choice of mFOLFOX6 or FOLFIRI Q2W ± bevacizumab or cetuximab. Treatment continued until PD, unacceptable toxicity, pt/investigator decision to withdraw, or completion of 35 cycles (pembro only). Pts receiving chemo could crossover to pembro for up to 35 cycles after confirmed PD. Primary end points were OS and PFS (RECIST v1.1, central review). Secondary end points included ORR, duration of response (DOR) (RECIST v1.1, central review), and safety. For OS significance, the p-value had to meet a prespecified α of 0.0246 (one-sided). Sensitivity analyses to adjust for crossover effect were performed. Data cut-off for final analysis was Feb 19, 2021. Results: Median (range) study follow-up was 44.5 mo (36.0-60.3) with pembro vs 44.4 mo (36.2-58.6) with chemo. 56 (36%) pts crossed over from chemo to pembro, with 37 more receiving anti-PD-1/PD-L1 therapies off study (60% effective crossover rate in the ITT). The HR for OS favored pembro vs chemo with a trend toward reduction in the risk of death (HR 0.74; 95% CI, 0.53-1.03; P=0.0359; median not reached [NR] vs 36.7 mo); this difference did not reach statistical significance. Sensitivity analysis by the rank-preserving structure failure time model and inverse probability of censoring weighting showed OS HRs of 0.66 (95% CI 0.42-1.04) and 0.77 (95% CI 0.44-1.38), respectively. Pembro vs chemo met the prespecified criteria for PFS superiority at IA2. At final analysis, median PFS was 16.5 mo vs 8.2 mo (HR 0.59; 95% CI, 0.45-0.79), but was not formally tested per analysis plan. Confirmed ORR was 45.1% (20 CR, 49 PR) vs 33.1% (6 CR, 45 PR). Median (range) DOR was NR (2.3+ to 53.5+) vs 10.6 mo (2.8 to 48.3+), respectively. Treatment-related adverse events (TRAEs) occurred in 79.7% vs 98.6% of pts; 21.6% vs 66.4%, respectively, had grade ≥3 TRAEs. Conclusions: As 1L therapy for pts with MSI-H/dMMR mCRC, pembro vs chemo provides statistically superior PFS with fewer TRAEs, and is associated with a trend toward reduced mortality that did not meet statistical significance likely due to the high crossover rate from chemo to anti-PD1/PD-L1 therapies. Together these data confirm pembro as a new standard-of-care in the 1L for pts with MSI-H/dMMR mCRC. Clinical trial information: NCT02563002.

Background: Leading scientific societies have recommended delaying and/or suspending active cancer treatment during the COVID-19 pandemic. Nevertheless, data on this novel infection in patients with a diagnosis of cancer receiving active treatment are scarce and it is unknown if these recommendations could have repercussions on future progress of the disease. The main objective of this study is to learn the COVID-19 incidence rate in outpatients with cancer receiving active treatment. Methods: This work is a retrospective cohort study that included all patients with a diagnosis of cancer who received active cancer treatment in two Andalusian hospitals between February 26 and May 13, 2020. Variables regarding the patient, tumor, and development of COVID-19 were collected. A descriptive analysis was performed and the cumulative incidence of COVID-19 in these patients was evaluated. Results: A total of 673 patients were included. The median age was 62 years. There was a low rate of comorbidity and 12.1% had an ECOG > 2. Breast cancer was the most common cancer (41%), followed by colorectal and lung cancer. Stage IV cancer was reported in 52.7% of patients. The most common treatment was chemotherapy (53.9%). Treatment was delayed or suspended in 6% of patients. Only three patients developed COVID-19. The cumulative incidence was 0.44% and one person died due to infection. Conclusions: In the present retrospective cohort study we found a low incidence of COVID-19 infection in patients with cancer receiving active treatment in an outpatient setting. The sociodemographic factors of Andalusia may explain why these results differ from those presented by other colleagues in Spain, but raise questions about whether universal recommendations may put the benefits of antineoplastic therapy at risk. (c) 2021 Elsevier Inc. All rights reserved.

Background Adoptive immunotherapy with tumour-infiltrating lymphocytes (TIL) may benefit from the use of selective markers, such as PD-1, for tumour-specific T-cell enrichment, and the identification of predictive factors that help identify those patients capable of rendering tumour-reactive TILs. We have investigated this in ovarian cancer (OC) patients as candidates for TIL therapy implementation. Methods PD-1 − and PD-1 + CD8 TILs were isolated from ovarian tumours and expanded cells were tested against autologous tumour cells. Baseline tumour samples were examined using flow cytometry, multiplexed immunofluorescence and Nanostring technology, for gene expression analyses, as well as a next-generation sequencing gene panel, for tumour mutational burden (TMB) calculation. Results Tumour-reactive TILs were detected in half of patients and were exclusively present in cells derived from the PD-1 + fraction. Importantly, a high TIL density in the fresh tumour, the presence of CD137 + cells within the PD-1 + CD8 + TIL subset and their location in the tumour epithelium, together with a baseline T-cell-inflamed genetic signature and/or a high TMB, are features that identify patients rendering tumour-reactive TIL products. Conclusion We have demonstrated that PD-1 identifies ovarian tumour-specific CD8 TILs and has uncovered predictive factors that identify OC patients who are likely to render tumour-specific cells from PD-1 + TILs.

Introduction and Objectives: Cancer patients are more susceptible to infections because of the active treatmentthat they need to treat their disease A new coronavirus, called SARS-CoV-2, has caused a global pandemic wherecancer patients have an increased risk of morbidity and mortality associated with COVID-19 However, the incidencedata of COVID-19 in cancer patient with active treatment are not known, although the main oncology societiesrecommend a delay and/or stop in active cancer treatment during this pandemic Whether this stop will have animpact on the future evolution of their disease is also not known Therefore, a study of the incidence of COVID-19 inthis type of patient can help us to organize the protocols and the treatment in these high-risk patient group Materials and Methods: We conducted a prospective clinical study of cancer patients within active treatment(chemotherapy, palliative hormonotherapy, radiotherapy, target therapies, or immunotherapy), analyzing the numberof COVID-19 diagnoses between February 26 and May 13 in two oncology services of the Andalusian community Adescriptive analysis of 692 patients with active treatment was carried out In addition, the cumulative incidence andthe differences between groups were calculated using the SPSS vs 18 Results: A total of 692 cancer patients undergoing active treatment at the Hospital Costa del Sol (Marbella) and atthe Hospital San Cecilio (Granada) were analyzed Sixty four percent were men with a mean age of 60 years Fortyone percent had a breast cancer diagnosis, 12 9% had lung cancer, and 14 5% had colorectal tumor Fifty threepercent of them received treatment for stage IV disease, and up to 43% were delayed treatment due to pandemic The total number of infections was 9, a cumulative incidence of 1 3%, 95% CI (0 384-2 217), and 22% of them diedafter developing the infection Advanced age (p = 0 011), an admission in the 3 months prior to the diagnosis ofCOVID-19 (p = 0 031), and active treatment with chemotherapy (p = 0 003) were the factors that were associated with an increased risk of developing COVID-19 Conclusions: The incidence of SARS-CoV-2 in cancer patients on active treatment is low but the mortality is high, as previously reported for these patients Given that the incidence of COVID-19 in patients with treatment is low, wecannot conclude any role of treatment delay in the development of COVID-19 in these patients

Abstract Introduction and Objectives: Cancer patients are more susceptible to infections because of the active treatment that they need to treat their disease. A new coronavirus, called SARS-CoV-2, has caused a global pandemic where cancer patients have an increased risk of morbidity and mortality associated with COVID-19. However, the incidence data of COVID-19 in cancer patient with active treatment are not known, although the main oncology societies recommend a delay and/or stop in active cancer treatment during this pandemic. Whether this stop will have an impact on the future evolution of their disease is also not known. Therefore, a study of the incidence of COVID-19 in this type of patient can help us to organize the protocols and the treatment in these high-risk patient group. Materials and Methods: We conducted a prospective clinical study of cancer patients within active treatment (chemotherapy, palliative hormonotherapy, radiotherapy, target therapies, or immunotherapy), analyzing the number of COVID-19 diagnoses between February 26 and May 13 in two oncology services of the Andalusian community. A descriptive analysis of 692 patients with active treatment was carried out. In addition, the cumulative incidence and the differences between groups were calculated using the SPSS vs 18. Results: A total of 692 cancer patients undergoing active treatment at the Hospital Costa del Sol (Marbella) and at the Hospital San Cecilio (Granada) were analyzed. Sixty four percent were men with a mean age of 60 years. Forty one percent had a breast cancer diagnosis, 12.9% had lung cancer, and 14.5% had colorectal tumor. Fifty three percent of them received treatment for stage IV disease, and up to 43% were delayed treatment due to pandemic. The total number of infections was 9, a cumulative incidence of 1.3%, 95% CI (0.384-2.217), and 22% of them died after developing the infection. Advanced age (p = 0.011), an admission in the 3 months prior to the diagnosis of COVID-19 (p = 0.031), and active treatment with chemotherapy (p = 0.003) were the factors that were associated with an increased risk of developing COVID-19. Conclusions: The incidence of SARS-CoV-2 in cancer patients on active treatment is low but the mortality is high, as previously reported for these patients. Given that the incidence of COVID-19 in patients with treatment is low, we cannot conclude any role of treatment delay in the development of COVID-19 in these patients. Citation Format: Celia Martin Bravo, Isabel Blancas López-Barajas, Raúl Quirós López, Marta Robles Lasarte, Rosa Villatoro Roldán, Julia Alcaide García, Victor Navarro Pérez, Diego Perez Martín, Irene Zarcos Pedrinaci, Elisa Mañas Mora, Nicolás Jiménez García, Santiago Vico Cabra, Irati de Urrutia Undabarrena, Isabel Barragan Mallofret, Cristina Quero Blanco, Elisabeth Pérez-Ruiz. Incidence of SARS-COV-2 infection in cancer patients undergoing active treatment [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-024.

Recent studies suggest that long-interspersed nucleotide element-1 (LINE-1) hypomethylation is commonly found in colorectal cancer (CRC), and is associated with worse prognosis. However, the utility of LINE-1 methylation on the prognosis of CRC is still controversial, and may be due to the fact that some clinical and pathological features may affect LINE-1 methylation. Thus, the aim of this study was to assess the prognostic value of tumor LINE-1 methylation in CRC, through their association with the CRC clinical and pathological characteristics. Survival of sixty-seven CRC patients was evaluated according to the median of tumor LINE-1 methylation, as well as pathological and oncological variables. We also studied the association between LINE-1 methylation and pathological features, and finally, we assessed the overall and disease-free survival of LINE1 methylation, stratified by neoadjuvant treatment and further checked by multivariate Cox regression to assess the statistical interactions. LINE-1 was hypomethylated in the CRC tumor with respect to the tumor adjacent-free area (p < 0.05), without association with any other clinical and oncological features, nor with overall and disease-free survival rates for CRC. Relevantly, in neoadjuvant treatment, LINE-1 methylation was associated with survival rates. Thus, disease-free and overall survival rates of treated CRC patients were worse in the hypomethylated LINE-1 tumors than those with normal LINE-1 methylation (p = 0.004 and 0.0049, respectively). Indeed, LINE-1 was hypermethylated more in the treated patients than in the non-treated patients (p < 0.05). The present study showed that tumor LINE-1 hypomethylation was associated with worse survival rates in only treated patients. Our data suggest an interactive effect of neoadjuvant treatment and tumor LINE-1 methylation, which could be a specific-tissue biomarker to predict survival of the treated patients, and help to personalize treatment in CRC.

15 Background: Accurate genotyping is mandatory for the management of mCRC pts. Tissue-based testing is still the SoC; however, is not available for all pts. and may be exhausted by serial testing, resulting in incomplete genotyping. We aimed to establish the validity of comprehensive non-invasive ctDNA testing in 1L mCRC pts for whom SoC tissue genotyping was available. Methods: 1L mCRC pts were tested with a comprehensive ctDNA test (Guardant360), a RAS ctDNA test (OncoBeam), and SoC tissue testing at the time of diagnosis. The primary endpoint was NCCN guideline biomarker discovery rate ( KRAS, NRAS, and BRAF mutations, ERBB2 amplification, and microsatellite instability). Results: In 91 evaluable pts, the biomarker discovery rate was 54.9% (50/91) for SoC tissue testing, 59.3% (54/91) for comprehensive ctDNA testing ( p= 0.0318 for non-inferiority vs. SoC), and 42.9% (39/91) for RAS ctDNA testing (inferiority not rejected vs. SoC). Both comprehensive and RAS ctDNA testing showed high positive agreement (85%, 44/52, and 86%, 31/36) and negative agreement (96%, 268/279, and 93%, 93/100) relative to SoC tissue testing at the gene level. Expanding genotyping beyond KRAS codon 12/13 mutations increased biomarker discovery rate by 56% for tissue testing (50/91 vs. 32/91, McNemar’s p< 0.0001) and by 64% for comprehensive ctDNA (54/91 vs. 33/91, McNemar’s p< 0.0001). Turnaround time was significantly shorter for comprehensive ctDNA testing vs. SoC tissue testing (mean 11.7 days vs. 23.0 days, paired T-test p= 0.0002). On retrospective analysis, 92% of biomarker-positive pts would have been identified at 2 weeks using the comprehensive ctDNA test for initial genotyping with reflex to tissue for biomarker-negative pts, whereas initial use of SoC tissue testing would have identified only 85% of positive pts at 4 weeks (Fisher’s exact p< 0.0001). Conclusions: As previously reported for lung cancer, comprehensive ctDNA testing in 1L mCRC identifies at least as many biomarker-positive pts as SoC tissue genotyping with high concordance to tissue and in half the turnaround time.

Among the prognostic factors relevant to the condition of oncological patients, nutritional status (NS) has the greatest single impact on quality of life (QL). The goals of our study were to evaluate the influence of NS, weight loss (WL), and the presence of cachexia, prior to the initiation of chemotherapy, on the patient’s QL. Adult patients (aged ≥ 18 years) diagnosed with solid tumours for whom chemotherapy was started between April 2016 and June 2017 were eligible for inclusion in the study. They were asked to complete a QL questionnaire (Functional Assessment of Cancer Treatment (FACT-G)) at the beginning. The presence or absence of cachexia was evaluated at the outset, following the definition proposed by Fearon and nutritional assessment by the Patient-Generated Subjective Global Assessment (PG-SGA) scale. A total of 177 patients completed the FACT-G, the 60% receiving curative therapy. At the start of the treatment, 58.2% of patients had experienced WL, with an average of 4.4 ± 7.4%, and 19% were at risk of malnutrition. Patient who presented cachexia at diagnosis, were treated with palliative intention, had a Nutriscore ≥ 5 points or presented malnutrition in accordance with PG-SGA had a poorer QL (p < 0.05). Greater WL was associated with a worsened QL (p = 0.001). Breast cancer patients presented an inverse correlation between the %WL and the initial score in the FACT-G (r = − 0.304, p = 0.023), whereas no such correlation was observed for the other types of tumour (r = − 0.012, p = 0.892). These results underline the relation of NS before starting chemotherapy and QL. Greater WL was associated with a worsened QL, especially in women with breast cancer.

AIMSthe aim of this study was to examine the possible association between the type of hospital admission and subsequent survival of the patient, as well as the pathological features recorded in a large population of patients with colorectal cancer.METHODSthe study included 1,079 patients diagnosed with colon or rectal cancer in the Hospital Costa del Sol (Marbella, Spain). The relationship between patient survival rate and type of first admission to the hospital (elective or emergency admission) was assessed. The following variables were studied: age, gender, tumor location, pathological stage, differentiation grade, chemotherapy before surgery and survival.RESULTScolon tumors are more common in patients admitted to hospital for the first time via the emergency service (63.7%) and the tumors tend to be poorly differentiated (64.2%) and metastatic (70%). These patients also present a more aggressive disease and a poorer prognosis than patients with an elective admission. With regard to patients from the Emergency Department, a Cox regression analysis showed a risk-ratio (RR) of 1.36 (confidence interval [CI] 95%: 1.11-1.66) for disease-free survival and of 1.41 (95% CI: 1.14-1.76) for overall survival.CONCLUSIONShospital admission via the Emergency Department is an indicator of aggressiveness and poorer prognosis compared to patients who enter via programmed routes.

Introduction: Few studies have been conducted to establish the relationship between colorectal cancer screening programmes and survival adjusting by stage and, to determine whether there are differences, at a biological level, between the tumours of asymptomatic and symptomatic patients. Accordingly, the aim of this study is to evaluate clinical, biological and survival differences between symptomatic colorectal tumours and those detected by screening. Study method: A prospective cohort study was performed of patients subjected to surgical intervention during the period 2010-2012, at different hospitals in Spain. In every case, clinical, pathological, biological and survival-related variables were obtained. Results: A total of 2634 patients from the CARESS-CCR cohort were analysed; of these, 220 were diagnosed through screening. The asymptomatic patients were younger, had a higher Body Mass Index (BMI), a lower degree of perineural invasion and a less advanced T stage and nodular stage, and the tumour was frequently located on the right side of the colon. All of these differences were statistically significant. The serum tumour marker carbohydrate antigen 19.9 (CA 19.9) was found more frequently in the symptomatic patients (p < 0.05). However, no significant differences were found regarding the markers of tumour biology: Ki67 (proliferation), CD105 (angiogenesis) and the Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay (apoptosis). The patients with asymptomatic tumours had a lower mortality at five years than those diagnosed presenting symptoms. Conclusions: The detection method employed influenced the survival of patients with colorectal cancer and there were no significant biological differences between the study groups. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.