Time intervals between U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) new cancer therapy approvals.

1575 Background: Novel therapies are transforming cancer care. Regulatory review and approval are essential to deliver safe and efficacious innovations to patients. Studies prior to 2010 describe quicker approval decisions for new oncology drug registrations with the FDA compared to the EMA (median delay 238 days). Both regulatory agencies have subsequently improved procedures to expedite approval times. We compared regulatory market authorisation dates at the FDA and EMA for new oncology therapies from 2010-2020. Methods: New oncology therapeutic approvals between 2010-2020 were identified from the FDA and EMA regulatory databases. We analysed only initial approvals (not supplementary licenses) for active anti-cancer therapies (excluding biosimilars and supportive drugs). The delay in regulatory approval between the FDA and EMA was calculated in calendar days. We further analysed therapies by therapeutic class, evaluating for significant differences. Results: We identified 108 new therapy registrations during the study period. 104 (96.3%) therapies were approved by the FDA and 90 (83.3%) had EMA market authorisation. 4 (3.7%) drugs were not FDA registered, including 3 unsuccessful applications and 1 which sought licensing in a different indication. 18 (16.5%) drugs were not EMA registered, including 9 (8.8%) which did not pursue EMA licensing, 3 (2.9%) withdrawn licensing applications, 3 (2.9%) sought licensing in different tumour group/indication, 1 (0.9%) rejected application and 2 (1.9%) with applications under review at submission date. Of the 86 drugs approved by both agencies, 80 were approved first by the FDA and 6 by the EMA. The median delay in approval between the FDA and EMA was 227 days (IQR:124-354 days). Table shows approvals by therapeutic class. The shortest median time difference for approval was for monoclonal antibodies (171 days) with the longest for kinase inhibitors (281 days). Conclusions: This study shows more new oncology therapies are approved by the FDA than the EMA. Patients in the US typically have access to approved therapies earlier than in Europe. From 2010 to 2020 the median delay between FDA and EMA approval was 227 days, falling by 11 days compared to 2003-10, [non-statistically significant]. Such lengthy delays could exceed the life expectancy of many patients with advanced cancer. Innovations for accelerated approval at both the FDA (e.g. Project Orbis) and EMA (e.g., PRIME) have potential to lead to faster approval.[Table: see text]

The Management of Peutz–Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline

The scientific data to guide the management of Peutz–Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane. Evidence levels and recommendation strengths were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A Delphi process was followed, with consensus being reached when ≥80% of the voting guideline committee members agreed. Recommendations and statements: The only recent guidelines available were for gastrointestinal and pancreatic management. These were reviewed and endorsed after confirming that no more recent relevant papers had been published. Literature searches were performed for additional questions and yielded a variable number of relevant papers depending on the subject addressed. Additional recommendations and statements were formulated. Conclusions: A decade on, the evidence base for recommendations remains poor, and collaborative studies are required to provide better data about this rare condition. Within these restrictions, multisystem, clinical management recommendations for PJS have been formulated.

Hepatic perivascular epithelioid cell tumours in children with tuberous sclerosis

Perivascular epithelioid cell tumours are a novel histological description of mesenchymal tumours consisting of perivascular and epithelioid cells. Angiomyolipomas are one of the commoner types of this tumour group. They are typically associated with the inherited condition tuberous sclerosis (TS). In TS they are often seen arising in the kidneys and brain, although much more rarely can be seen in the liver. While usually thought of as benign tumours there is little evidence to predict whether they will progress to malignancy. Currently, there is no recommended best management strategy between resection and surveillance. We report two patients with TS seen in our centre with these described PEComa liver lesions histologically, however only one required a resection. On review of the literature, features such as increased size, rapid growth and vascular invasion would be concerning for possible malignant potential and therefore merit resection, as well as significant symptoms.

QOL-21. DEVELOPMENT AND UTILISATION OF A NEURO-ONCOLOGY REHABILITATION TEAM: 2018–2019 UPDATE

INTRODUCTION A multi-disciplinary Neuro-Oncology Rehabilitation Team (NORT) was established at our institution in 2014. We reviewed NORT inputs, processes and outputs in 2018 to 2019 compared to our previously presented data from 2015, soon after service inception. METHODS Retrospective analysis of patients who received NORT input June 2018 - May 2019 compared to 2015 data. Descriptive analysis of changes to NORT operational processes and structure. Complexity of rehabilitation needs was measured using the Rehabilitation Complexity Scale-Extended V13 (RCS). RESULTS 54 children received NORT input in 2018–2019 (10 children in 2015) with total of 129 outputs. NORT input was highest in children with high grade glioma (median reviews: 3; median RCS: 5) and ependymoma (median reviews: 3; median RCS: 5). Pilocytic astrocytoma formed the largest tumour group (n = 11; median reviews: 2; median RCS: 7). 11% patients were referred to neurologist (9% already known); 17% referred to community services (44% already known); 31% referred to neuropsychology. In 2015, outputs were predominantly referral to occupational therapy and physiotherapy. 6 patients (11% of 54) were discharged in 2018–2019 (40% of 10 patients in 2015). 4 patients died. Between 2015 and 2019, developments included: clarifying referral and discharge pathways, use of screening measures, neuropsychology integration, therapy-led drop-in clinics, use of RCS-E. DISCUSSION: There has been a clear increase in utilisation and scope of work of NORT over last 4 years. The strength of this team is multidisciplinary working and expertise. Further developments planned: multidisciplinary rehabilitation interventions and NORT outcome tools.

Nonlinear analysis of scalp EEGs from normal and brain tumour subjects

Measurement of features from the chaos theory or as popularly known, the concept of nonlinear dynamics, as indicatives of several pathological conditions and cognition states using the electroencephalography (EEG) signal is very popular. In this paper, the analysis of scalp EEG signals of normal subjects and brain tumour patients using the nonlinear dynamic features has been presented. The nonlinear dynamic features that represent the dimensional and waveform complexities of the signal being analyzed have been considered. The statistical analysis of the selected nonlinear dynamic features has been presented. The results show that the nonlinear dynamic features significantly discriminate the brain tumour group from the normal group.

The outcome of Pregnancy with Fetal Primitive Neuroectodermal Tumor

BACKGROUND: Fetal intracranial tumours are very rare. The overall incidence is 0.34 per one thousand live birth newborns. According to the new classification of central nervous system tumour (2016), a primitive neuroectodermal tumour of (PNETs) is an embryonal tumour group; these are tumours with high malignancy and belong to group IV (WHO). In our case, we will present a case of PNETs in 28 gestation week old fetus, diagnosed antenatally and confirmed postnatally.CASE REPORT: We present the third pregnancy in 29 years old patient, with two previous term deliveries of healthy newborn. She came to University clinic at 27+3 gestational week for fetal hydrocephalus. After an ultrasound and MRI scan, possibilities were explained to the parents. During the medico-ethical counselling, explain to the parents the need for operation and the possibility of postoperative adjuvant therapy, quality of life with potential future disabilities. They choose to terminate the pregnancy. Postmortem the diagnosis was PNETs. Summary of analysis: peripheral neuroectodermal tumour with ganglion and neuronal differentiationCONCLUSION: Antenatal management depends on the gestational week in the time of diagnosis and the decision of parents. If the lesion is before viability fetus, it should be offered termination of pregnancy. Another important factor is the mode of delivery, because of increased intracranial pressure although this aggressive combined modality of treatment, recurrence is often. Tree year of survival is between 53% and 73% when the adjuvant radiotherapy is included. For that, they should be diagnosed as soon as possible before achieving fetal viability. Only 18% of those tumours presenting in the first year of life are diagnosed before or at delivery.