Protocol for a systematic review with prospective individual patient data meta-analysis in EGFR-mutant NSCLC with brain metastases to assess the effect of SRS+osimertinib compared to osimertinib alone: the STARLET Collaboration.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice. METHODS: Randomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform's Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups. ETHICS AND DISSEMINATION: Approved by each trial's ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION: CRD42022330532.

Differential diagnosis of brain lesions in a metastatic endometrial carcinosarcoma patient.

The differential diagnosis of ring-enhancing brain lesions in a patient with metastatic malignancy may initially seem straightforward, and easily attributed to brain metastases. On rare occasions, the physician needs to avoid anchoring bias by re-evaluating the entire clinical context in which these ring-enhancing brain lesions are found. We report a case of cerebral toxoplasmosis mimicking brain metastases in a patient with metastatic cancer and without a prior history of human immunodeficiency virus. A 65-year-old lady with a recently detected relapse of her endometrial carcinosarcoma presented with a 2-week history of fever with no localising symptoms or signs of infection. The initial investigations were unremarkable. She had daily fever despite empirical broad-spectrum antibiotics. A positron emission tomography-computed tomography (PET-CT) was performed to evaluate the pyrexia of unknown origin, which showed metastatic deposits in the pelvis. A magnetic resonance imaging (MRI) of the brain was subsequently performed due to fluctuating mentation, which reported metastatic disease to the brain. Her pyrexia of unknown origin was attributed to malignancy-related fever. The medical oncologist was cautious about starting systemic treatment because the PET-CT had FDG-avid diffuse ground glass opacities in both lung fields, and requested for a bronchoscopic evaluation, which returned positive for Pneumocystis jirovecii. In light of this new finding, a multi-disciplinary discussion and a review of the brain MRI were undertaken, during which it was concluded that the likelihood of cerebral toxoplasmosis was much higher than brain metastases. She was treated with high dose trimethoprim-sulfamethoxazole for both P. jirovecii pneumonia and cerebral toxoplasmosis, with clinical and radiological improvement. This case highlights the importance of (a) clinical input in interpreting imaging findings, (b) entertaining the possibility of multiple concurrent pathologies explaining a patient's symptoms, (c) being open to alternate diagnoses when new information surfaces even though the current working diagnosis is the most plausible and (d) multi-disciplinary communication when faced with diagnostic difficulty.

Visceral obesity in Asian living kidney donors significantly impacts early renal function after donor nephrectomy.

INTRODUCTION: Obesity may be a risk factor for kidney donors to develop reduced renal function. The Framingham heart study suggested that visceral adipose tissue (VAT) confers a more adverse metabolic profile compared with subcutaneous adipose tissue (SAT). Asians tend to have a higher VAT composition and it is unclear if their kidney function is affected differently. We hypothesized that Asian living kidney donors who have visceral obesity are at a higher risk of renal function deterioration 1 year after donation. METHODS: Between 2011 and 2014, we retrospectively evaluated data from 73 consecutive patients (52% male; mean age 44.9 ± 11.7 years) before they underwent donor nephrectomy and at their 1 year routine follow-up. VAT and SAT were measured at the level of the umbilicus on pre-operative computerized tomography (CT). Visceral obesity (VO) was defined as a VAT > 100 cm [2] and patients were then further divided and compared in two subgroups: VAT > 100 and < 100 cm [2]. Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m [2]) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation pre-operatively and 1 year post-operatively. RESULTS: Both subgroups had similar baseline kidney function (P = NS) pre-operatively. At the 1 year follow-up, patients with VO experienced a more significant decline of renal function (109 ± 9 to 89 ± 8 mL/min per 1.73 m2), compared to those without VO (111 ± 12 to 96 ± 11 mL/min per 1.73 m2, P = 0.013). VO was associated with a body mass index (BMI) > 25 kg/m2 (P < 0.001), male gender (P < 0.001) and older age at the time of donor nephrectomy (48.0 vs 39.5 years, P = 0.01). The presence of hypertension or hyperlipidaemia pre-operatively, choice of surgical approach, and post-operative complication rates, did not differ significantly between the subgroups. CONCLUSIONS: Visceral obesity as defined by VAT > 100 cm2 at the level of the umbilicus on cross-sectional imaging, may have a significant impact on early renal function after donor nephrectomy. Adiposity markers, as measured by cross-sectional CT imaging, may be incorporated into routine pre-operative kidney donor workup.

Diagnosis and Management of Radiation Necrosis in Patients With Brain Metastases.

The use of radiotherapy, either in the form of stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), remains the cornerstone for the treatment of brain metastases (BM). As the survival of patients with BM is being prolonged, due to improved systemic therapy (i.e., for better extra-cranial control) and increased use of SRS (i.e., for improved intra-cranial control), patients are clinically manifesting late effects of radiotherapy. One of these late effects is radiation necrosis (RN). Unfortunately, symptomatic RN is notoriously hard to diagnose and manage. The features of RN overlap considerably with tumor recurrence, and misdiagnosing RN as tumor recurrence may lead to deleterious treatment which may cause detrimental effects to the patient. In this review, we will explore the pathophysiology of RN, risk factors for its development, and the strategies to evaluate and manage RN.