Dataset Information

Is mTOR Inhibitor Good Enough for Treatment All Tumors in TSC Patients?

ABSTRACT: Tuberous sclerosis complex (TSC) is an autosomal dominant and multi-system genetic disorder in humans. TSC affects around 25,000 to 40,000 individuals in the United States and about 1 to 2 million individuals worldwide, with an estimated prevalence of one in 6,000 newborns. TSC occurs in all races and ethnic groups, and in both genders. TSC is caused by defects or mutations in two genes, TSC1 and TSC2. Loss of TSC1/TSC2 leads to dysregulation of mTOR, resulting in aberrant cell differentiation and development, and abnormal enlargement of cells. TSC is characterized by the development of benign and/or malignant tumors in several organs including renal/liver angiomyolipomas, facial angiofibroma, lymphangiomyomatosis, cardiac rhabdomyomas, retinal astrocytic, renal cell carcinoma, and brain subependymal giant cell astrocytomas (SEGA). In addition, TSC disease causes disabling neurologic disorders, including epilepsy, mental retardation and autism. Particularly problematic are the development of renal angiomyolipomas, which tend to be larger, bilateral, multifocal and present at a younger age compared with sporadic forms. In addition, SEGA block the flow of fluid within the brain, causing a buildup of fluid and pressure that leads to blurred vision and seizures. In the current review, we describe the pathology of TSC disease in key organs and summarize the use of mTOR inhibitors to treat tumors in TSC patients.

SUBMITTER: Habib SL

PROVIDER: S-EPMC5039383 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Is mTOR Inhibitor Good Enough for Treatment All Tumors in TSC Patients?

Habib Samy L SL Al-Obaidi Noor Y NY Nowacki Maciej M Pietkun Katarzyna K Zegarska Barbara B Kloskowski Tomasz T Zegarski Wojciech W Drewa Tomasz T Medina Edward A EA Zhao Zhenze Z Liang Sitai S

Journal of Cancer 20160721 12

Tuberous sclerosis complex (TSC) is an autosomal dominant and multi-system genetic disorder in humans. TSC affects around 25,000 to 40,000 individuals in the United States and about 1 to 2 million individuals worldwide, with an estimated prevalence of one in 6,000 newborns. TSC occurs in all races and ethnic groups, and in both genders. TSC is caused by defects or mutations in two genes, TSC1 and TSC2. Loss of TSC1/TSC2 leads to dysregulation of mTOR, resulting in aberrant cell differentiation a ...[more]

PMID: 27698899

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Project description:BackgroundNon-inferiority and equivalence trials aim to determine whether a new treatment is good enough (non-inferior) or as good as (equivalent to) another treatment. To inform the decision about non-inferiority or equivalence, a margin is used. We aimed to identify the current methods used to determine non-inferiority or equivalence margins, as well as the main challenges and suggestions from trialists.MethodsWe developed an online questionnaire that included both closed and open-ended questions about methods to elicit non-inferiority or equivalence margins, underlying principles, and challenges and suggestions for improvement. We recruited trialists with experience of determining a margin by contacting corresponding authors for non-inferiority or equivalence trials. We used descriptive statistics and content analysis to identify categories in qualitative data.ResultsWe had forty-one responses, all from non-inferiority trials. More than half of the trials were non-pharmacological (n = 21, 51%), and the most common primary outcome was clinical (n = 29, 71%). The two most used methods to determine the margin were as follows: a review of the evidence base (n = 27, 66%) and opinion seeking methods (n = 24, 59%). From those using reviews, the majority used systematic reviews or reviews of multiple RCTs to determine the margin (n = 17, 63%). From those using opinion seeking methods, the majority involved clinicians with or without other professionals (n = 19, 79%). Respondents reported that patients' opinions on the margin were sought in four trials (16%). Median confidence in overall quality of the margin was 5 out of 7 (maximum confidence); however, around a quarter of the respondents were "completely unconfident" that the margin reflected patient's views. We identified "stakeholder involvement" as the most common category to determine respondent's confidence in the quality of the margins and whether it reflected stakeholder's views. The most common suggestion to improve the definition of margins was "development of methods to involve stakeholders," and the most common challenge identified was "communication of margins."ConclusionsResponders highlighted the need for clearer guidelines on defining a margin, more and better stakeholder involvement in its selection, and better communication tools that enable discussions about non-inferiority trials with stakeholders. Future research should focus on developing best practice recommendations.

Dataset Information

Is mTOR Inhibitor Good Enough for Treatment All Tumors in TSC Patients?

Publications

Is mTOR Inhibitor Good Enough for Treatment All Tumors in TSC Patients?

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