Complete genomic characterization in patients with cancer of unknown primary origin in routine diagnostics.

BACKGROUND: In ∼3%-5% of patients with metastatic disease, tumor origin remains unknown despite modern imaging techniques and extensive pathology work-up. With long diagnostic delays and limited and ineffective therapy options, the clinical outcome of patients with cancer of unknown primary (CUP) remains poor. Large-scale genome sequencing studies have revealed that tumor types can be predicted based on distinct patterns of somatic variants and other genomic characteristics. Moreover, actionable genomic events are present in almost half of CUP patients. This study investigated the clinical value of whole genome sequencing (WGS) in terms of primary tumor identification and detection of actionable events, in the routine diagnostic work-up of CUP patients. PATIENTS AND METHODS: A WGS-based tumor type 'cancer of unknown primary prediction algorithm' (CUPPA) was developed based on previously described principles and validated on a large pan-cancer WGS database of metastatic cancer patients (>4000 samples) and 254 independent patients, respectively. We assessed the clinical value of this prediction algorithm as part of routine WGS-based diagnostic work-up for 72 CUP patients. RESULTS: CUPPA correctly predicted the primary tumor type in 78% of samples in the independent validation cohort (194/254 patients). High-confidence predictions (>95% precision) were obtained for 162/254 patients (64%). When integrated in the diagnostic work-up of CUP patients, CUPPA could identify a primary tumor type for 49/72 patients (68%). Most common diagnoses included non-small-cell lung (n = 7), gastroesophageal (n = 4), pancreatic (n = 4), and colorectal cancer (n = 3). Actionable events with matched therapy options in clinical trials were identified in 47% of patients. CONCLUSIONS: Genome-based tumor type prediction can predict cancer diagnoses with high accuracy when integrated in the routine diagnostic work-up of patients with metastatic cancer. With identification of the primary tumor type in the majority of patients and detection of actionable events, WGS is a valuable diagnostic tool for patients with CUP.

A project for the evaluation of awareness of under-aged patients involved in clinical trials. Development of the IGG- Awareness Scale.

AIM: Most very sick, under-aged children express a desire or need for information about their illness and therapy. Most of them are being treated with experimental trials, and their parents/ tutors have been requested to provide informed consent. The need to understand, mostly by the older patients, may differ depending on age and gender, but it always involves psychology. Although the literature is full of guidelines and papers about assent of under-aged patients, there is a lack of data about their awareness. METHODS: The authors report a project for the evaluation of awareness of under-aged patients in their involvement in clinical trials; a simple investigative instrument that consists of a short, simple, semistructured interview which includes a questionnaire of 11 items is presented. A preliminary investigation was performed with a convenience sample of 15 school-aged children with cancer. The interview project was accomplished after this evaluation. The main aim was to evaluate the degree of awareness of sick youngsters between 11 and 18 years of age with regards to the experimental trial they are undergoing. RESULTS AND CONCLUSIONS: The study is a monocentric, transversal and descriptive survey, approved by the Research Ethics Committee of our institution. A complete analysis of the total scores of awareness will be performed.

[Microcalcification and breast pathology: differential diagnosis and oncogenic risk assessment]. / Le microcalcificazioni nella patologia mammaria: diagnosi differenziale e valutazione del rischio oncogeno.

Breast cancer is one of the first cause of death in women. The investigation and the study of microcalcifications can discover about half of hidden breast carcinomas and this is an excellent help for the diagnosis. The aim of this study is to give some guidelines for a correct interpretation of these microcalcifications.

[Supraventricular tachycardia in children]. / Le tachicardie sopraventricolari nell'infanzia.

Supraventricular tachycardia is one of the most frequent arrhythmias in childhood. It may accompany congenital heart disease. W.P. W. syndrome, or a normal state of health. A re-entry circuit is the most commonly observed electrophysiological mechanism. Persistence is followed by decompensation. Drug management is based on digitalis, ATP, amiodarone, and verapamil. Atrial and ventricular pacing and surgery are alternatives when other means fail. Persistent tachycardia (i.e. its presence over long periods) is much less frequent that the paroxysmal form, and its aetiology is generally unknown. Even here, the clinical picture is substantially related to decompensation. Digitalis + amiodarone is the best treatment, though the arrhythmia may resolve spontaneously.