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Background and study aims  Colorectal cancer is one of the most common malignancies, with approximately 20 % of patients having metastatic disease. Local symptoms from the tumor remain a common issue and affect quality of life. Electroporation is a method to permeabilize cell membranes with high-voltage pulses, allowing increased passage of otherwise poorly permeating substances such as calcium. The aim of this study was to determine the safety of calcium electroporation for advanced colorectal cancer. Patients and methods  Six patients with inoperable rectal and sigmoid colon cancer were included, all presenting with local symptoms. Patients were offered endoscopic calcium electroporation and were followed up with endoscopy and computed tomography/magnetic resonance scans. Biopsies and blood samples were collected at baseline and at follow-up, 4, 8, and 12 weeks after treatment. Biopsies were examined for histological changes and immunohistochemically with CD3/CD8 and PD-L1. In addition, blood samples were examined for circulating cell-free DNA (cfDNA). Results  A total of 10 procedures were performed and no serious adverse events occurred. Prior to inclusion, patients reported local symptoms, such as bleeding (N = 3), pain (N = 2), and stenosis (N = 5). Five of six patients reported symptom relief. In one patient, also receiving systemic chemotherapy, clinical complete response of primary tumor was seen. Immunohistochemistry found no significant changes in CD3 /CD8 levels or cfDNA levels after treatment. Conclusions  This first study of calcium electroporation for colorectal tumors shows that calcium electroporation is a safe and feasible treatment modality for colorectal cancer. It can be performed as an outpatient treatment and may potentially be of great value for fragile patients with limited treatment options., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Purpose: The clinical potential of liquid biopsy in patients with advanced cancer is real-time monitoring for early detection of treatment failure. Our study aimed to investigate the clinical validity of circulating tumor DNA (ctDNA) treatment monitoring in a real-life cohort of patients with advanced non-small cell lung cancer (NSCLC)., Experimental Design: Patients with advanced or noncurative locally advanced NSCLC were prospectively included in an exploratory study (NCT03512847). Selected cancer-specific mutations were measured in plasma by standard or uniquely designed droplet digital PCR assays before every treatment cycle during first-line treatment until progressive disease (PD). Correlation between an increase in ctDNA (= molecular progression) and radiologic PD was investigated, defined as lead time, and the corresponding numbers of likely futile treatment cycles were determined. Utility of ctDNA measurements in clarifying the results of nonconclusive radiologic evaluation scans was evaluated., Results: Cancer-specific mutations and longitudinal plasma sampling were present in 132 of 150 patients. ctDNA was detectable in 88 (67%) of 132 patients treated by respectively chemotherapy ( n = 41), immunotherapy ( n = 43), or combination treatment ( n = 4). In 66 (90%) of 73 patients experiencing PD, a ctDNA increase was observed with a median lead time of 1.5 months before radiologic PD. Overall, 119 (33%) of 365 treatment cycles were administered after molecular progression. In addition, ctDNA measurements could clarify the results in 38 (79%) of 48 nonconclusive radiologic evaluations., Conclusions: ctDNA monitoring leads to earlier detection of treatment failure, and clarifies the majority of nonconclusive radiologic evaluations, giving the potential of sparing patients from likely futile treatments and needless adverse events., Significance: Treatment monitoring by ctDNA has the clinical potential to reveal PD before radiologic evaluation and consequently spare patients with advanced cancer from likely ineffective, costly cancer treatments and adverse events., Competing Interests: M.S. Frank reports grants from Changing Cancer Care, funded through Interreg Deutschland-Denmark by the European Regional Development Fund, The ctDNA Research Center, IMK Almene Foundation, Agnethe Løvgreens Legacy, Dagmar Marshalls Foundation, Danish Research Center for Lung Cancer, Fabrikant Einar Willumsens Foundation, Skibsreder Per Henriksen, R. og Hustrus Foundation, The Neye Foundation, Eva and Henry Fr aenkels Foundation, and Naestved, Slagelse and Ringsted Hospitals’ Research Funds during the conduct of the study. N. Pallisgaard reports personal fees from Amgen Denmark outside the submitted work. J. Gehl reports grants from Changing Cancer Care, funded through Interreg Deutschland-Denmark by the European Regional Development Fund and The ctDNA Research Center during the conduct of the study. No disclosures were reported by the other authors., (© 2022 The Authors; Published by the American Association for Cancer Research.)