COGNITION: a prospective precision oncology trial for patients with early breast cancer at high risk following neoadjuvant chemotherapy.

BACKGROUND: COGNITION (Comprehensive assessment of clinical features, genomics and further molecular markers to identify patients with early breast cancer for enrolment on marker driven trials) is a diagnostic registry trial that employs genomic and transcriptomic profiling to identify biomarkers in patients with early breast cancer with a high risk for relapse after standard neoadjuvant chemotherapy (NACT) to guide genomics-driven targeted post-neoadjuvant therapy. PATIENTS AND METHODS: At National Center for Tumor Diseases Heidelberg patients were biopsied before starting NACT, and for patients with residual tumors after NACT additional biopsy material was collected. Whole-genome/exome and transcriptome sequencing were applied on tumor and corresponding blood samples. RESULTS: In the pilot phase 255 patients were enrolled, among which 213 were assessable: thereof 48.8% were identified to be at a high risk for relapse following NACT; 86.4% of 81 patients discussed in the molecular tumor board were eligible for a targeted therapy within the interventional multiarm phase II trial COGNITION-GUIDE (Genomics-guided targeted post neoadjuvant therapy in patients with early breast cancer) starting enrolment in Q4/2022. An in-depth longitudinal analysis at baseline and in residual tumor tissue of 16 patients revealed some cases with clonal evolution but largely stable genetic alterations, suggesting restricted selective pressure of broad-acting cytotoxic neoadjuvant chemotherapies. CONCLUSIONS: While most precision oncology initiatives focus on metastatic disease, the presented concept offers the opportunity to empower novel therapy options for patients with high-risk early breast cancer in the post-neoadjuvant setting within a biomarker-driven trial and provides the basis to test the value of precision oncology in a curative setting with the overarching goal to increase cure rates.

[Small-cell sarcoma of the esophagus as a fourth malignancy. Its palliative therapy with argon gas coagulation]. / Kleinzelliges Sarkom des Osophagus als viertes Malignom. Palliative Therapie mit Argongaskoagulation.

HISTORY: A prostatic carcinoma, an early gastric carcinoma and a colon carcinoma had occurred over 15 years in a now 82-year-old patient. He was now admitted because of severe dysphagia. INVESTIGATIONS: Gastroscopy revealed an exophytic tumour of the oesophagus, histologically identified as a small-cell sarcoma. It had caused a 12 cm long severe eccentric stenosis of the oesophagus. Tissue from the previous three tumours were examined immunohistochemically for p-53 gene mutation, but only the oesophageal sarcoma gave positive results. TREATMENT AND COURSE: After part of exophytic tumour had been ablated by argon gas coagulation a prosthetic tube was implanted. Bleeding from erosion of a large metastasis in the gastric fundus was successfully treated by argon gas coagulation 4 months after the previous discharge, but the patient died of the malignancy 1/1 and half months later. CONCLUSIONS: The consecutive occurrence of four different malignant tumours is rare even in advanced age. In this case the malignancies were presumably unrelated and it demonstrates the possibility of removing an eccentric tumour stenosis by argon gas coagulation before implanting a prosthesis.

[Spontaneous rupture of an umbilical hernia in decompensated liver cirrhosis]. / Spontanruptur einer Umbilikalhernie bei dekompensierter Leberzirrhose.

The case of a spontaneous rupture of an umbilical hernia of a 52 year old patient, secondary to cirrhosis of the liver, is described as a rare complication of portal hypertension with massive ascites. Additionally a survey of the literature is given.