13 research outputs found
TuberOus SClerosis registry to increase disease Awareness (TOSCA) â baseline data on 2093 patients
Angiomiolipoma; Epilepsia; TOSCAAngiomyolipoma; Epilepsy; TOSCAAngiomyolipoma; EpilĂšpsia; TOSCABackground
Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Many gaps remain in the understanding of TSC because of the complexity in clinical presentation. The TuberOus SClerosis registry to increase disease Awareness (TOSCA) is an international disease registry designed to address knowledge gaps in the natural history and management of TSC. Here, we present the baseline data of TOSCA cohort.
Methods
Patients of any age diagnosed with TSC, having a documented visit for TSC within the preceding 12 months, or newly diagnosed individuals were included. The registry includes a âcoreâ section designed to record detailed background information on each patient including disease manifestations, interventions, and outcomes collected at baseline and updated annually. âSubsectionsâ of the registry recorded additional data related to specific features of TSC.
Results
Baseline âcoreâ data from 2093 patients enrolled from 170 sites across 31 countries were available at the cut-off date September 30, 2014. Median age of patients at enrollment was 13 years (range, 0â71) and at diagnosis of TSC was 1 year (range, 0â69). The occurrence rates of major manifestations of TSC included â cortical tubers (82.2%), subependymal nodules (78.2%), subependymal giant cell astrocytomas (24.4%), renal angiomyolipomas (47.2%), lymphangioleiomyomatosis (6.9%), cardiac rhabdomyomas (34.3%), facial angiofibromas (57.3%), forehead plaque (14.1%), â„ 3 hypomelanotic macules (66.8%), and shagreen patches (27.4%). Epilepsy was reported in 1748 (83.5%) patients, of which 1372 were diagnosed atââ€â2 years (78%). Intellectual disability was identified in 451 (54.9%) patients of those assessed. TSC-associated neuropsychiatric disorders (TAND) were diagnosed late, and not evaluated in 30â50% of patients.
Conclusion
TOSCA is the largest clinical case series of TSC to date. It provided a detailed description of the disease trajectory with increased awareness of various TSC manifestations. The rates of different features of TSC reported here reflect the age range and referral patterns of clinics contributing patients to the cohort. Documentation of TAND and LAM was poor. A widespread adoption of the international TSC assessment and treatment guidelines, including use of the TAND Checklist, could improve surveillance. The registry provides valuable insights into the necessity for monitoring, timing, and indications for the treatment of TSC.This study was funded by Novartis Pharma AG
Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib
This multicentre phase II trial (DOVIGIST) evaluated the antitumour activity of dovitinib as second-line treatment of patients with gastrointestinal stromal tumour (GIST) refractory to imatinib or who do not tolerate imatinib. Patients received oral dovitinib 500mgday1, 5 days on/2 days off, until GIST progression or unacceptable toxicity, with an objective to evaluate efficacy, assessed as the disease control rate (DCR) at 12 weeks. Tumour assessment and response to dovitinib therapy were evaluated by Response Evaluation Criteria In Solid Tumours (RECIST v1.1) and the Choi criteria. Secondary objectives included assessment of progression-free survival (PFS), safety and tolerability, and DCR at the end of treatment. Thirty-eight of the 39 patients enrolled had histologically confirmed GIST. The DCR at 12 weeks was 52.6% (90% confidence interval (CI), 38.2-66.7%) meeting the preset efficacy criterion for the primary end point. The objective response rate (complete responsepartial response) was 2.6% (1 of 38; 90% CI, 0.1-11.9%), and 5.3% (n=2; 90% CI, 0.9-15.7%) at the end of the study. The median PFS was 4.6 months (90% CI, 2.8-7.4 months). Dose interruption was required in 26 patients (66.7%), of which 18 (69.2%) were due to adverse events. The most frequently observed grade 3 adverse events included hypertension (n=7), fatigue (n=5), vomiting (n=4), hypertriglyceridaemia (n=4), and g-glutamyltransferase increase (n=4). Dovitinib is an active treatment for patients with GIST who are intolerant to imatinib or whose GIST progresses on imatinib
EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex
Background: Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to be effective and safe in the treatment of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC). The Everolimus For Fast Expanded aCcess in TSC SEGA (EFFECTS) study was designed to provide everolimus access to patients with SEGA associated with TSC and to mainly assess the safety and also efficacy of everolimus in a real-world setting. Methods: EFFECTS was a phase 3b, open-label, noncomparative, multicenter, expanded access study. Eligible patients wereââ„â3Â years of age, with a definite diagnosis of TSC, and with at least one SEGA lesion identified by MRI or CT scan. Patients received once daily everolimus (dose adjusted to attain a trough level of 5-15Â ng/mL). Safety evaluation was the primary objective and included collection of adverse events (AEs) and serious AEs, with their severity and relationship to everolimus. Efficacy evaluation, which was the secondary objective, was based on the best overall response as per medical judgment. Results: Of the 120 patients enrolled, 100 (83.3%) completed the study. Median age of patients was 11Â years (range, 1-47). Median daily dose of everolimus was 5.82Â mg (range, 2.0â11.8). Median duration of exposure was 56.5Â weeks (range, 0.3â130). The overall incidence of AEs was 74.2%. Aphthous stomatitis (18 [15.0%]), pyrexia (18 [15.0%]), bronchitis (11 [9.2%]), and stomatitis (10 [8.3%]) were the most common AEs reported. Overall, 25 patients had grade 3 AEs; most frequent was stomatitis (4 [3.3%]). Grade 4 AEs were reported in three (2.5%) patients. A total of 62 (51.7%) patients had suspected drug-related AEs, of which 15 (12.5%) were of grade 3 or 4. In eight (6.7%) patients, AEs led to drug discontinuation. With regard to efficacy, 81 (67.5%) patients had a partial response, 35 (29.2%) had a stable disease, and one (0.8%) had progressive disease. The response was unknown in three (2.5%) patients. Conclusion: This study confirms the acceptable safety profile of everolimus in patients with SEGA associated with TSC in a real-world setting. The results further support the efficacy of everolimus in the treatment of SEGA associated with TSC. (EudraCT: 2010-022583-13
TOSCA â first international registry to address knowledge gaps in the natural history and management of tuberous sclerosis complex
Abstract
Background
Tuberous sclerosis complex (TSC) is a rare, multisystem, genetic disorder with an estimated prevalence between 1/6800 and 1/15000. Although recent years have seen huge progress in understanding the pathophysiology and in the management of TSC, several questions remain unanswered. A disease registry could be an effective tool to gain more insights into TSC and thus help in the development of improved management strategies.
Methods
TuberOus SClerosis registry to increase disease Awareness (TOSCA) is a multicentre, international disease registry to assess manifestations, interventions, and outcomes in patients with TSC. Patients of any age diagnosed with TSC, having a documented visit for TSC within the preceding 12Â months, or newly diagnosed individuals are eligible. Objectives include mapping the course of TSC manifestations and their effects on prognosis, identifying patients with rare symptoms and co-morbidities, recording interventions and their outcomes, contributing to creation of an evidence-base for disease assessment and therapy, informing further research on TSC, and evaluating the quality of life of patients with TSC. The registry includes a âcoreâ section and subsections or âpetalsâ. The âcoreâ section is designed to record general information on patientsâ background collected at baseline and updated annually. Subsections will be developed over time to record additional data related to specific disease manifestations and will be updated annually. The registry aimed to enrol approximately 2000 patients from about 250 sites in 31 countries. The initial enrolment period was of 24Â months. A follow-up observation period of up to 5Â years is planned.
Results
A pre-planned administrative analysis of âcoreâ data from the first 100 patients was performed to evaluate the feasibility of the registry. Results showed a high degree of accuracy of the data collection procedure. Annual interim analyses are scheduled. Results of first interim analysis will be presented subsequent to data availability in 2014.
Implications
The results of TOSCA will assist in filling the gaps in understanding the natural history of TSC and help in planning better management and surveillance strategies. This large-scale international registry to study TSC could serve as a model to encourage planning of similar registries for other rare diseases
From correlation to causation: analysis of metabolomics data using systems biology approaches
TuberOus SClerosis registry to increase disease Awareness (TOSCA) â baseline data on 2093 patients
Abstract Background Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Many gaps remain in the understanding of TSC because of the complexity in clinical presentation. The TuberOus SClerosis registry to increase disease Awareness (TOSCA) is an international disease registry designed to address knowledge gaps in the natural history and management of TSC. Here, we present the baseline data of TOSCA cohort. Methods Patients of any age diagnosed with TSC, having a documented visit for TSC within the preceding 12 months, or newly diagnosed individuals were included. The registry includes a âcoreâ section designed to record detailed background information on each patient including disease manifestations, interventions, and outcomes collected at baseline and updated annually. âSubsectionsâ of the registry recorded additional data related to specific features of TSC. Results Baseline âcoreâ data from 2093 patients enrolled from 170 sites across 31 countries were available at the cut-off date September 30, 2014. Median age of patients at enrollment was 13 years (range, 0â71) and at diagnosis of TSC was 1 year (range, 0â69). The occurrence rates of major manifestations of TSC included â cortical tubers (82.2%), subependymal nodules (78.2%), subependymal giant cell astrocytomas (24.4%), renal angiomyolipomas (47.2%), lymphangioleiomyomatosis (6.9%), cardiac rhabdomyomas (34.3%), facial angiofibromas (57.3%), forehead plaque (14.1%), â„ 3 hypomelanotic macules (66.8%), and shagreen patches (27.4%). Epilepsy was reported in 1748 (83.5%) patients, of which 1372 were diagnosed at †2 years (78%). Intellectual disability was identified in 451 (54.9%) patients of those assessed. TSC-associated neuropsychiatric disorders (TAND) were diagnosed late, and not evaluated in 30â50% of patients. Conclusion TOSCA is the largest clinical case series of TSC to date. It provided a detailed description of the disease trajectory with increased awareness of various TSC manifestations. The rates of different features of TSC reported here reflect the age range and referral patterns of clinics contributing patients to the cohort. Documentation of TAND and LAM was poor. A widespread adoption of the international TSC assessment and treatment guidelines, including use of the TAND Checklist, could improve surveillance. The registry provides valuable insights into the necessity for monitoring, timing, and indications for the treatment of TSC
Efficacy and safety of everolimus in patients with advanced low- or intermediate-grade pancreatic neuroendocrine tumors previously treated with chemotherapy: RADIANT-3 subgroup analysis.
Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib
Background: This multicentre phase II trial (DOVIGIST) evaluated the antitumour activity of dovitinib as second-line treatment of patients with gastrointestinal stromal tumour (GIST) refractory to imatinib or who do not tolerate imatinib. Methods: Patients received oral dovitinib 500 mg day(-1), 5 days on/2 days off, until GIST progression or unacceptable toxicity, with an objective to evaluate efficacy, assessed as the disease control rate (DCR) at 12 weeks. Tumour assessment and response to dovitinib therapy were evaluated by Response Evaluation Criteria In Solid Tumours (RECIST v1.1) and the Choi criteria. Secondary objectives included assessment of progression-free survival (PFS), safety and tolerability, and DCR at the end of treatment. Results: Thirty-eight of the 39 patients enrolled had histologically confirmed GIST. The DCR at 12 weeks was 52.6% (90% confidence interval (CI), 38.2-66.7%) meeting the preset efficacy criterion for the primary end point. The objective response rate (complete response+partial response) was 2.6% (1 of 38; 90% CI, 0.1-11.9%), and 5.3% (n = 2; 90% CI, 0.9-15.7%) at the end of the study. The median PFS was 4.6 months (90% CI, 2.8-7.4 months). Dose interruption was required in 26 patients (66.7%), of which 18 (69.2%) were due to adverse events. The most frequently observed grade 3 adverse events included hypertension (n = 7), fatigue (n = 5), vomiting (n = 4), hypertriglyceridaemia (n = 4), and gamma-glutamyltransferase increase (n = 4). Conclusions: Dovitinib is an active treatment for patients with GIST who are intolerant to imatinib or whose GIST progresses on imatinib.Peer reviewe
HistĂČria grĂ fica de la Segarra
DirecciĂł: Max Turull Rubinat ; coordinaciĂł: Elena Armengol Cera ... [et al.] ; selecciĂł i textos: M. Dolors AlluĂ© Albareda ... [et al.].El volum que teniu a les mans representa i Ă©s, sens dubte, el testimoni grĂ fic mĂ©s complet de la nostra historia recent, reflex fidel d'un temps pretĂšrit, perĂČ no tan allunyant per a nosaltres, entranyable per tot un seguit de raons i, naturalment, emotiu en tots els ordres per a tots aquells que conformen part d'aquesta comunitat segarrenca. Al llarg de les seves pagines, que ens transporten en un viatge imaginen, es pot recĂłrrer el que ha estat la historia de la comarca, els esdeveniments mĂ©s importants que varen succeir, les festes i tradicions, moltes encara avui, sortosament, arrelades i altres, malauradament, desaparegudes. TambĂ© es pot reviure el
desenvolupament de les activitats de tota mena, tant econĂČmiques com industrials, educatives, laborals, etc., que representaven els pilars fonamentals de la vida econĂČmica i social de la Segarra..