A universal cell-free DNA approach for response prediction to preoperative chemoradiation in rectal cancer.

The standard treatment approach for stage II/III rectal cancer is neoadjuvant chemoradiation therapy (nCRT) followed by surgery. In recent years, new treatment approaches have led to higher rates of complete tumor eradication combined with organ-preservation strategies. However, better tools are still needed to personalize therapy for the individual patient. In this prospective observational study, we analyzed colon-derived cell-free (cf)DNA (c-cfDNA) using a tissue-specific DNA methylation signature, and its association with therapy outcomes. Analyzing plasma samples (n = 303) collected during nCRT from 37 patients with locally advanced rectal cancer (LARC), we identified colon-specific methylation markers that discriminated healthy individuals from patients with untreated LARC (area under the curve, 0.81; 95% confidence interval, 0.70-0.92; P < .0001). Baseline c-cfDNA predicted tumor response, with increased levels linked to larger residual cancer. c-cfDNA measured after the first week of therapy identified patients with maximal response and complete cancer eradication, who had significantly lower c-cfDNA compared with those who had residual disease (8.6 vs 57.7 average copies/ml, respectively; P = .013). Increased c-cfDNA after 1 week of therapy was also associated with disease recurrence. Methylation-based liquid biopsy can predict nCRT outcomes and facilitate patient selection for escalation and de-escalation strategies.

[THE MAGIC OF IMMUNOTHERAPY - ANTI-PD1 TREATMENT IN ADENOCARCINOMA OF THE GASTROESOPHAGEAL JUNCTION].

INTRODUCTION: Adenocarcinomas of the gastroesophageal junction (GEJ) are tumors whose incidence rates increased significantly in recent years. These tumors have a poor prognosis, and are treated with a palliative approach when diagnosed in an advanced stage. Some tumors overexpress PDL-1 proteins which are partially responsible for the "immune escape" of tumor cells. However, this over-expression enables the use of an immunotherapeutic treatment approach. Immunotherapy using anti-PD1/PDL-1 shows promising results in patients with metastatic GEJ tumors. In the present case report, we describe a young patient who was diagnosed with a non-resectable GEJ adenocarcinoma and was found to have almost 100% positivity for PDL-1 in the tumor biopsy, using standard immunohistochemistry. The patient had rapid and complete response to the anti-PD1 antibody treatment with further development of immune mediated side effects.