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PURPOSETo better understand immigration disparities among a Spanish Early-Onset Colorectal Cancer (SECOC) subset, according to the country of origin.PATIENTS AND METHODSWe selected 250 consecutive participants from the SECOC consortium. Data on baseline patient and tumor characteristics, family history of colorectal cancer (CRC), and follow-up were collected. The presence of mismatch repair deficiency was also assessed. Special data regarding country of origin, time of stay in Spain in case of other different country, and a 10-year cutoff that specifies the obtaining of Spanish nationality defined the variables of interest for comparison.RESULTSSeventy-five percent of patients with early-onset CRC (EOCRC) (188) were born in Spain, whereas the other 25% were born outside of Spain. The mean time of living in Spain until the EOCRC diagnosis was 16.5 years. Comparatively, most of the analyzed features showed equivalent proportions between cohorts. Only Spanish patients appeared to have more familial cancer component in first degree in general (32.3%; P = .01), compared with non-Spaniards, which showed a predominant sporadic component (56.4%; P < .001). Among immigrants, those patients living in Spain before CRC diagnosis ≤10 years were younger at diagnosis (39.1 v 42.5), more frequently male (77.8 v 47.7), were in more advanced stages (88.8% diagnosed at stage III and IV [P = .01]), and had a worse prognosis regarding recurrence rates (29.4% v 6.3%).CONCLUSIONAlthough there were few differences between Spanish and non-Spanish EOCRC, the most remarkable difference was that linked with the situation of those immigrants who have recently arrived in Spain, in relation to their lower health coverage, which could be associated with the delay in the diagnosis and their subsequent worse prognosis.

Abstract Differential presence of exons (DPE) by next generation sequencing (NGS) is a method of interpretation of whole exome sequencing. This method has been proposed to design a predictive and diagnostic algorithm with clinical value in plasma from patients bearing colorectal cancer (CRC). The aim of the present study was to determine a common exonic signature to discriminate between different clinical pictures, such as non-metastatic, metastatic and non-disease (healthy), using a sustainable and novel technology in liquid biopsy. Through DPE analysis, we determined the differences in DNA exon levels circulating in plasma between patients bearing CRC vs. healthy, patients bearing CRC metastasis vs. non-metastatic and patients bearing CRC metastasis vs. healthy comparisons. We identified a set of 510 exons (469 up and 41 down) whose differential presence in plasma allowed us to group and classify between the three cohorts. Random forest classification (machine learning) was performed and an estimated out-of-bag (OOB) error rate of 35.9% was obtained and the predictive model had an accuracy of 75% with a confidence interval (CI) of 56.6–88.5. In conclusion, the DPE analysis allowed us to discriminate between different patho-physiological status such as metastatic, non-metastatic and healthy donors. In addition, this analysis allowed us to obtain very significant values with respect to previous published results, since we increased the number of samples in our study. These results suggest that circulating DNA in patient’s plasma may be actively released by cells and may be involved in intercellular communication and, therefore, may play a pivotal role in malignant transformation (genometastasis).

Ovarian cancer is the seventh most common cancer worldwide in women and the most lethal gynecologic malignancy due to the lack of accurate screening tools for early detection and late symptom onset. The absence of early-onset symptoms often delays diagnosis until the disease has progressed to advanced stages, frequently when there is peritoneal involvement. Although ovarian cancer is a heterogeneous malignancy with different histopathologic types, treatment for advanced tumors is usually based on chemotherapy and cytoreduction surgery. CAR T cells have shown promise for the treatment of hematological malignancies, though their role in treating solid tumors remains unclear. Outcomes are less favorable owing to the low capacity of CAR T cells to migrate to the tumor site, the influence of the protective tumor microenvironment, and the heterogeneity of surface antigens on tumor cells. Despite these results, CAR T cells have been proposed as a treatment approach for peritoneal carcinomatosis from colorectal and gastric origin. Local intraperitoneal administration of CAR T cells has been found to be superior to systemic administration, as this route is associated with increased tumor reduction, a more durable effect, protection against local relapse and distant metastases, and fewer systemic adverse effects. In this article we review the application of CAR T cells for the treatment of ovarian cancer and peritoneal carcinomatosis from ovarian cancer.

Background: Positive cytology has been identified as an independent negative prognostic factor in patients with peritoneal metastases (PM) of colorectal origin. Liquid biopsy in plasma may detect increasing levels of circulating tumor DNA (ctDNA) and could help predict systemic relapse in patients with colorectal cancer, but little is known about the role of liquid biopsy in peritoneal fluid. The aim of this study was to evaluate the prognostic value of peritoneal fluid and plasma liquid biopsy in patients undergoing complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CC-HIPEC). Methods: A longitudinal prospective study was designed in patients with KRAS- mutated colorectal or appendiceal primary tumor, including PM of colorectal origin, pseudomyxoma peritonei and patients at high risk of developing PM (selected for second-look surgery). Eleven patients were recruited according to inclusion and exclusion criteria. ctDNA from plasma and peritoneal fluid before and after HIPEC was studied by droplet digital PCR looking for KRAS mutation. A close follow-up was scheduled (mean of 28.5 months) to monitor for systemic and peritoneal recurrences. Results: All patients with positive plasma postHIPEC had systemic relapse and four patients died as a result, while those with negative plasma postHIPEC did not relapse. Patients with negative peritoneal ctDNA after CC-HIPEC did not present peritoneal relapse. Of six patients with positive peritoneal ctDNA postHIPEC, two presented peritoneal recurrence and four systemic relapses. Conclusions: Treatment with CC-HIPEC does not always neutralize ctDNA in peritoneal fluid, and its persistence after treatment may predict adverse outcome. Despite being a proof of concept, an adequate correlation between liquid biopsy in plasma and peritoneal fluid with both systemic and peritoneal relapse has been observed.

Differential presence of exons (DPE) is a method of interpretation of exome sequencing, which has been proposed to design a predictive algorithm with clinical value in patients with colorectal cancer (CRC). The goal of the present study was to examine the reproducibility in a rat model of metastatic colon cancer. DHD/K12-TRb cells were injected in syngenic immunocompetent BD-IX rats. Cells were from two stocks with low and normal metastatic potential, and injected into two separate groups of rats. Five to ten weeks after injection, blood samples were taken prior euthanasia and whole exome sequencing performed. Through DPE analysis, we identified a set of exons whose differential presence in plasma allowed us to compare both groups of tumor-bearing animals. A verification test was performed to confirm that the algorithm was able to classify extracted samples into their corresponding groups of origin. The highest mean probability was 0.8954. In conclusion, the DPE analysis in tumor-bearing animals was able to discriminate between different disease status, which fully supports previous results in CRC patients.

Background: Acellular pseudomyxoma peritonei ( a PMP) is a rare peritoneal malignancy characterized by the accumulation of large amounts of mucin (lacking tumor cells) in the peritoneum. Many cases account for several kilograms of mucin to be screened by the pathologist. This is a comprehensive study of three patients with a PMP, whose tumors showed KRAS mutation, allowing for the tracking of this marker by liquid biopsy. Methods: Pre and post-surgery plasma, and mucin removed during cytoreductive surgery were collected from the patients. KRAS mutations were analyzed using droplet digital polymerase chain reaction (ddPCR). Mucin was injected in mice. KRAS and cytokine levels were measured in plasma of the mice using ddPCR and a magnetic bead-based assay. Mucin microbiome was analyzed by 16S rRNA sequencing. Results: KRAS mutations were detected in mucin cell-free DNA (cfDNA) from the three patients but not in the pre or post-surgery plasma. Electron microscopy detected microparticles (diameter

Abstract Next‐generation sequencing (NGS) has been proposed as a suitable tool for liquid biopsy in colorectal cancer (CRC), although most studies to date have focused almost exclusively on sequencing of panels of potential clinically actionable genes. We evaluated the clinical value of whole‐exome sequencing (WES) of cell‐free DNA (cfDNA) circulating in plasma, with the goal of identifying differential clinical profiles in patients with CRC. To this end, we applied an original concept, “differential presence of exons” (DPE). We determined differences in levels of 379 exons in plasma cfDNA and used DPE analysis to cluster and classify patients with disseminated and localized disease. The resultant bioinformatics analysis pipeline allowed us to design a predictive DPE algorithm in a small subset of patients that could not be initially classified based on the selection criteria. This DPE suggests that these nucleic acids could be actively released by both tumor and nontumor cells as a means of intercellular communication and might thus play a role in the process of malignant transformation. DPE is a new technique for the study of plasma cfDNA by WES that might have predictive and prognostic value in patients with CRC.