Effectiveness and safety of everolimus treatment in patients with tuberous sclerosis complex in real-world clinical practice.

BACKGROUND: The randomised double-blinded placebo-controlled EXIST-1-3 studies have showed everolimus effective with adverse effects reported as acceptable in treatment of symptoms in patients with tuberous sclerosis complex (TSC), although evidence of outcomes in clinical practice remains limited. This study aimed to investigate, in clinical practice, the effectiveness and safety of everolimus for epilepsy, renal angiomyolipoma (rAML), and subependymal giant cell astrocytoma (SEGA) in patients with TSC. RESULTS: The study included 64 patients with TSC (median age: 19, range 0.9-54 years) receiving everolimus treatment (Norway: n = 35; Denmark: n = 29). Among 45 patients with epilepsy, 14 (31%) were responders experiencing ≥ 50% reduction in seizure frequency in the last 3 months of treatment compared with the last 3 months before treatment. Nineteen (42%) patients changed their anti-seizure medications (ASMs). Responders were more common among patients < 18 years (46%) than among patients ≥ 18 years (14%, p = 0.03). In 29 patients with rAML, everolimus reduced (≥ 30% decrease) and stabilized (< 20% increase, ≤ 30% decrease) longest diameter of rAML in 38% and 59%, respectively, after a mean treatment duration of 37 months. SEGA volume was reduced in three patients by 71%, 43%, and 48% after 39, 34, and 82 months. Adverse effects were reported in 61 of 64 patients (95%) after a median treatment duration of 31 months (range 0-106), with oral ulceration/stomatitis (63%) and upper respiratory tract infections (38%) being the most common. The most common laboratory abnormalities were increased cholesterol (41%), anaemia (30%), and leucopoenia (25%). Grade 3-4 adverse effects were reported in 36% of cases, and life-threatening conditions were reported in two patients. Nine patients discontinued everolimus treatment. CONCLUSIONS: Seizure reduction in this study sample was consistent with results from EXIST, but might be lower than expected, given that changes in concomitant ASMs are part of clinical practice. Seizure reduction was associated with younger age. As with EXIST, everolimus reduced or stabilised rAML size in most patients. SEGA volume was reduced in all three patients. Close follow-up is needed for this group, especially for children and patients who may not be able to report adverse effects.

Resection rates and intention-to-treat outcomes in borderline and locally advanced pancreatic cancer: real-world data from a population-based, prospective cohort study (NORPACT-2).

BACKGROUND: Systemic chemotherapy is the initial treatment strategy for borderline resectable and locally advanced pancreatic cancer to facilitate curative resection. The aim of this study was to investigate the resection rates and overall survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer. METHODS: Consecutive patients with borderline resectable pancreatic cancer/locally advanced pancreatic cancer discussed by Oslo University Hospital multidisciplinary team between 2018 and 2020, serving a population of 3.1 million within a geographically defined area in south-eastern Norway, were included in this prospective Norwegian Pancreatic Cancer Trial-2 study, according to intention-to-treat principles. The total number of patients with pancreatic cancer was sought from the Cancer Registry of Norway. RESULTS: A total of 1178 patients were diagnosed with pancreatic cancer, of whom 618 were referred to Oslo University Hospital. After multidisciplinary team evaluation, 230 patients were considered to have borderline resectable pancreatic cancer/locally advanced pancreatic cancer. The final study group consisted of 188 patients (borderline resectable pancreatic cancer n = 96, locally advanced pancreatic cancer n = 92) who were fit to receive primary chemotherapy. Resection rates were 46.9% (45 of 96) for borderline resectable pancreatic cancer and 13% (12 of 92) for locally advanced pancreatic cancer (P <0.001). Median overall survival was 14.6 months (borderline resectable pancreatic cancer 16.4 months; locally advanced pancreatic cancer 13.7 months, (P = 0.2)). Adjusted for immortal time bias, median overall survival for patients undergoing resection versus only chemotherapy was 24.4 months versus 10.1 months (P <0.001) for borderline resectable pancreatic cancer and 28.4 months versus 12.6 months for locally advanced pancreatic cancer (P = 0.001). CONCLUSION: Resection rates and survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer treated at a high-volume centre in a universal healthcare system compare well with those treated at international expert centres.Registration number: NCT04423731 (http://www.clinicaltrials.gov).

A man in his thirties with right ventricular heart failure, jaundice and abdominal pain. / En mann i 30-årene med høyresidig hjertesvikt, ikterus og magesmerter.

BACKGROUND: The combination of jaundice and acute abdominal pain is a common clinical problem associated with a broad array of aetiologies. CASE PRESENTATION: A 36-year-old male with Down's syndrome and Eisenmenger's syndrome presented with abdominal pain, jaundice and acute liver failure. Initial transabdominal ultrasound and subsequent magnetic resonance cholangiopancreatography (MRCP) revealed gallbladder stones, but no common bile duct stones. During the course of the patient's hospital admission, his liver chemistries were consistently elevated. Thus, endoscopic retrograde cholangiography (ERC) with sphincterotomy was performed, despite the anaesthesiological risk associated with his chronic heart failure. However, the ERC and sphincterotomy did not relieve the patient's symptoms and had no apparent effect on his abnormal liver chemistries. By the end of his hospital stay, the patient recovered spontaneously and was discharged with no final conclusion having been reached. An unexpected turn of events led us to conclude upon a diagnosis a few weeks later. INTERPRETATION: This case illustrates the challenges of a multidisciplinary approach in a complex patient, and an overlooked detail that became a lesson to learn from.