Monitoring with circulating tumor cells in the perioperative setting of patients with surgically treated stages I-IIIA NSCLC.

Background: Surgery is regarded as the treatment's cornerstone for early stage and locally advanced non-small cell lung cancer (NSCLC) whenever the tumor is considered resectable. Liquid biopsy is one of the most promising research areas in oncology in the last 10 years, providing a useful non-invasive tool to detect and monitor cancer. The prognostic value of circulating tumor cells (CTCs) has been studied in different cancer types and had been related with a higher risk of relapse and worse prognosis. The aim of this study is to evaluate the prognostic value of CTC detection in patients with stage I-IIIA NSCLC treated with surgery. Methods: We conducted a prospective, single-center study of 180 consecutive patients with resected and pathological confirmed stage I to IIIA (TNM AJCC/UICC 8th edition) NSCLC. Patients' blood samples were processed and CTCs were characterized before and after the surgery. A cohort of patients had CTC determination after chemotherapy and surgery. Cut-off points were established in 1 and 5 CTCs for statistical analysis. Results: A proportion of 76.7% had at least 1 CTC before the surgery, and 30.6% had 5 or more, while 55.9% had at least 1 CTC after surgery, and 8.3% had 5 or more. We found no correlation between preoperative CTC detection for a cut-off of 5 with neither overall survival (OS) [hazard ratio (HR): 0.99, P=0.887], disease-free survival (DFS) (HR: 0.95, P=0.39) nor relapse (32.7% vs. 28.8%, P=0.596). We also did not find a correlation between postoperative CTCs detection for a cut-off of 5 with either OS (HR: 1.01, P=0.808), DFS (HR: 0.95, P=0.952) or relapse (26.7% vs. 29.5%, P=0.83). The mean change in the number of CTCs over time between preoperative and postoperative samples was 2.13, with a standard deviation of 6.78. Conclusions: Despite the large cohort of patients included in this study, CTC monitoring in the perioperative setting was not correlated with relapse, DFS or OS in our study, and therefore cannot be recommended as a reliable biomarker for minimal residual disease (MRD) after surgery.

Long-term outcomes in Hodgkin lymphoma survivors. Temporary trends and comparison with general population.

The high cure rates of Hodgkin lymphoma (HL) make this oncological disease among those with the greatest number of long-term survivors. This single-institution study including 383 HL patients with up to 45 years of follow-up, analyses the morbidity and mortality of this population after treatments in comparison with the overall Spanish population, and investigates whether it has changed over time stratifying by periods of time, as a consequence of therapeutic optimization. The median age was 34.8 years (range 15-87) with median overall survival of 30 years, significantly higher in women (HR 0.58, 95% CI 0.42-0.79) (p = 0.0002). 185 late-stage diseases were noted (35% patients), cardiovascular disease (CVD) being the most frequent (23.2%). 30% of patients developed at least one second malignant neoplasm (SMN) to give a total of 174 SMNs. 20.9% of the patients died from HL and 67.0% died from non-HL causes (32.2% from SMN, 17% from CVD). The overall standardized mortality ratio (SMR) was 3.57 (95% CI: 3.0-4.2), with striking values of 7.73 (95% CI: 5.02-8.69) and of 14.75 (95% CI: 11.38-19.12) for women and patients <30 years at diagnosis, respectively. Excluding HL as the cause of death, the SMRs of those diagnosed before 2000 and from 2000 were proved to be similar (3.88 vs 2.73), maintaining in this last period an unacceptable excess of mortality due to secondary toxicity in patients cured of HL. Our study confirm that HL treatment substantially reduces the life expectancy of patients cured of HL. In recent periods, despite therapeutic optimization, deaths from toxicity continue to occur, mainly from CVD and SMN. Risk-factor monitoring should be intensified, prevention programs developed, and therapeutic optimization of LH investigated, especially in two vulnerable groups: those aged <30 years at diagnosis, and women.

ctDNA from body fluids is an adequate source for EGFR biomarker testing in advanced lung adenocarcinoma.

OBJECTIVES: Epidermal growth factor receptor (EGFR) biomarker testing using blood-based liquid biopsies remains challenging due to the low concentration of circulating tumor DNA (ctDNA) in certain plasma samples. The aim of this study is to evaluate the usefulness for EGFR biomarker testing of ctDNA from pleural effusions, cerebrospinal fluids, ascites and pericardial effusions obtained during the clinical management of lung adenocarcinoma patients. METHODS: For comparison purposes, 23 paired plasma and body fluid samples were collected from 17 patients with EGFR-positive lung adenocarcinoma. After circulating free DNA (cfDNA) isolation, samples were evaluated for the initial EGFR-sensitizing mutation and the p.T790M resistance mutation by array-based digital PCR (dPCR). RESULTS: Body fluids had more cfDNA than plasma samples (1.90 vs. 0.36 ng/µL; p=0.0130), and more samples tested positive for EGFR mutations (21 vs. 16 samples), with a total of 28 vs. 22 variants detected. Furthermore, mutant allele frequencies (MAFs) observed in body fluids were significantly higher than those assessed in the paired plasma samples for EGFR-sensitizing mutations (median MAFs = 15.8 vs. 0.8%; p=0.0004) as well as for the p.T790M resistance mutation (median MAFs = 8.69 vs. 0.16%; p=0.0390). Importantly, two patients who had progressed on first-generation EGFR-tyrosine kinase inhibitors with a dubious result for p.T790M plasma (MAFs = 0.11%) had an indisputably positive result in their respective body fluid samples (MAFs = 10.25 and 9.66%). CONCLUSIONS: ctDNA derived from body fluids is an informative source for EGFR biomarker testing, with greater sensitivity than plasma samples.