Baseline results from the UK SIGNIFY study: a whole-body MRI screening study in TP53 mutation carriers and matched controls.

In the United Kingdom, current screening guidelines for TP53 germline mutation carriers solely recommends annual breast MRI, despite the wide spectrum of malignancies typically seen in this group. This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomatic TP53 mutation carriers. 44 TP53 mutation carriers and 44 population controls were recruited. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed in TP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. In TP53 mutation carriers, 6 of 44 (13.6, 95% CI 5.2-27.4%) participants were diagnosed with cancer during the study, all of which would be considered life threatening if untreated. Two were found to have two primary cancers. Two participants with cancer had abnormalities on the MRI which were initially thought to be benign (a pericardial cyst and a uterine fibroid) but transpired to be sarcomas. No controls were diagnosed with cancer. Fifteen carriers (34.1, 95% CI 20.5-49.9%) and seven controls (15.9, 95% CI 6.7-30.1%) underwent further investigations following the WB MRI for abnormalities that transpired to be benign (p = 0.049). The cancer detection rate in this group justifies a minimum baseline non-contrast WB MRI in germline TP53 mutation carriers. This should be adopted into national guidelines for management of adult TP53 mutation carriers in addition to the current practice of contrast enhanced breast MRI imaging.

Is radiofrequency ablation more effective than stereotactic ablative radiotherapy in patients with early stage medically inoperable non-small cell lung cancer?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'is radiofrequency ablation more effective than stereotactic ablative radiotherapy in patients with early stage medically inoperable non-small cell lung cancer?' Altogether, over 219 papers were found, of which 16 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Radiofrequency ablation (RFA) and stereotactic ablative radiotherapy (SABR) offer a clear survival benefit compared with conventional radiotherapy in the treatment of early stage non-small cell lung cancer (NSCLC) in medically inoperable patients. Overall survival at 1 year (68.2-95% vs. 81-85.7%) and 3 years (36-87.5% vs. 42.7-56%) was similar between patients treated with RFA and SABR. However, 5-year survival was higher in SABR (47%) than RFA (20.1-27%). Local progression rates were lower in patients treated with SABR (3.5-14.5% vs. 23.7-43%). Both treatments were associated with complications. Pneumothorax (19.1-63%) was the most common complication following RFA. Fatigue (31-32.6%), pneumonitis (2.1-12.5%) and chest wall pain (3.1-12%) were common following SABR. Although tumours ≤ 5 cm in size can be effectively treated with RFA, results are better for tumours ≤ 3 cm. One study documented increased recurrence rates with larger tumours and advanced disease stage following RFA. Another study found increasing age, tumour size, previous systemic chemotherapy, previous external beam radiotherapy and emphysema increased the risk of toxicity following SABR and suggested that risk factors should be used to stratify patients. RFA can be performed in one session, whereas SABR is more effective if larger doses of radiation are given over two to three fractions. RFA is not recommended for centrally based tumours. Patients with small apical tumours, posteriorly positioned tumours, peripheral tumours and tumours close to the scapula where it may be difficult to position an active electrode are more optimally treated with SABR. Treatment for early stage inoperable NSCLC should be tailored to individual patients, and under certain circumstances, a combined approach may be beneficial.