Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillance.

BACKGROUND: Radiotherapy is a valuable treatment in the management algorithm of pituitary adenomas and craniopharyngiomas. However, the risk of second brain tumour following radiotherapy is a major concern. We assessed this risk using non-irradiated patients with the same primary pathology and imaging surveillance as controls. METHODS: In this multicentre, retrospective cohort study, 4292 patients with pituitary adenoma or craniopharyngioma were identified from departmental registries at six adult endocrine centres (Birmingham, Oxford, Leeds, Leicester, and Bristol, UK and Ferrara, Italy). Patients with insufficient clinical data, known genetic predisposition to or history of brain tumour before study entry (n=532), and recipients of proton beam or stereotactic radiotherapy (n=81) were excluded. Data were analysed for 996 patients exposed to 2-dimensional radiotherapy, 3-dimensional conformal radiotherapy, or intensity-modulated radiotherapy, and compared with 2683 controls. FINDINGS: Over 45 246 patient-years, second brain tumours were reported in 61 patients (seven malignant [five radiotherapy, two controls], 54 benign [25 radiotherapy, 29 controls]). Radiotherapy exposure and older age at pituitary tumour detection were associated with increased risk of second brain tumour. Rate ratio for irradiated patients was 2·18 (95% CI 1·31-3·62, p<0·0001). Cumulative probability of second brain tumour was 4% for the irradiated and 2·1% for the controls at 20 years. INTERPRETATION: Irradiated adults with pituitary adenoma or craniopharyngioma are at increased risk of second brain tumours, although this risk is considerably lower than previously reported in studies using general population controls with no imaging surveillance. Our data clarify an important clinical question and guide clinicians when counselling patients with pituitary adenoma or craniopharyngioma on the risks and benefits of radiotherapy. FUNDING: Pfizer.

COVID-19 and Adenovirus Multi-Lobar Pneumonia on CT Scan in a Patient with Repeatedly Normal Chest X-Rays Despite Severe Hypoxia and the Need for Non-Invasive Ventilation.

The British Society of Thoracic Imaging (BSTI) has published clear guidance on the classification of chest X-ray (CXR) findings in coronavirus disease 2019 (COVID-19) patients, which are summarised in four main categories: COVID-classical, COVID-indeterminate, COVID-normal, or non-COVID. We report the case of a 34-year-old lady who is otherwise fit and well. She presented with typical COVID-19 symptoms requiring supplemental oxygen, with normal CXR and COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) swab on admission. Her condition deteriorated after 24 hours with severe hypoxia requiring up to 60% oxygen. Repeat CXR was normal, which was followed by computed tomography pulmonary angiogram (CTPA) that ruled out pulmonary embolism; however, CTPA confirmed multi-lobar pneumonia consistent with COVID-19. The patient was admitted to the intensive care unit for non-invasive ventilation (NIV) and ongoing care. Extended respiratory screening confirmed positive COVID-19 antibodies and positive adenovirus swabs. The patient also developed COVID-19 related hepatocellular injury and myocarditis in the absence of other causes. These were treated by a multidisciplinary team, and the patient achieved full recovery after three weeks. This case highlights the fact that normal CXR does not rule out COVID-19 pneumonia even in the severely hypoxic patient requiring NIV. Also, it is important to investigate for other potential causes of hypoxia in a deteriorating patient, such as pulmonary embolism and non-COVID causes of pneumonia.