Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative.

BACKGROUND: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. MATERIAL AND METHODS: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. RESULTS: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. CONCLUSION: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting.

[Skin eruptions as an adverse reaction to epidermal growth-factor receptor inhibitors]. / Huidafwijkingen als bijwerking van remmers van epidermale-groeifactorreceptor.

Inhibition of the epidermal growth-factor receptor (EGFR) is a new strategy in the treatment of solid malignancies. Two men, aged 65 and 59 years, with a metastasized renal carcinoma and a 51-year-old man with a metastasized melanoma developed an acneiform eruption during EGFR inhibition. The second and third patient also developed paronychia. Treatment in all patients consisted of antiseptics and topical antibiotics; the first and third patient also received an oral antibiotic. Withdrawal of the EGFR inhibitor because of progression of the disease led to complete recovery of the cutaneous lesions in the first and the third patient; both died after several months. In the second patient, the side effects reached an acceptable level during continued EGFR therapy. EGFR inhibition is usually accompanied by cutaneous side effects. An acneiform eruption is seen in up to 90% of all treated patients. Other side effects include dry skin, and nail and hair changes. The pathogenesis of these side effects is related to inhibition of EGFR signalling pathways in the skin, but is not yet fully understood. The treatment of EGFR inhibitor-mediated cutaneous toxicity is based mainly on clinical experience.

Unexpected overdose with diltiazem: value of toxicological screening.

We describe a 59-year-old woman who was admitted in deep coma with bradycardia, hypotension and fixed pupils. The cause of her severe condition was unclear. Cerebral and myocardial infarction was excluded. Temporary transcutaneous pacing was not successful, nor was atropine or norepinephrine (noradrenaline), but the patient responded well to isoprenaline infusion. Since she was known to have a psychiatric history, toxicological screening was performed which showed a severe diltiazem overdose. Later we discovered that she took diltiazem for angina pectoris. The patient survived and was discharged without neurological or cardiological deficits after two days of treatment. This case report emphasises the importance of toxicological screening in unconscious patients with no apparent cause. We review the clinical features and treatment options of diltiazem overdose and discuss the value of toxicological screening.