Clinical outcome data for symptomatic breast cancer: the Breast Cancer Clinical Outcome Measures (BCCOM) Project.
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ABSTRACT:
SUBMITTER: Bates T
PROVIDER: S-EPMC2720241 | biostudies-other | 2009 Aug
REPOSITORIES: biostudies-other
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Project description:BackgroundDespite its first description over 40 years ago, knowledge of the clinical course of isovaleric acidemia (IVA), a disorder predisposing to severe acidotic episodes during catabolic stress, is still anecdotal. We aimed to investigate the phenotypic presentation and factors determining the neurological and neurocognitive outcomes of patients diagnosed with IVA following clinical manifestation.MethodsRetrospective data on 21 children and adults with symptomatic IVA diagnosed from 1976 to 1999 were analyzed for outcome determinants including age at diagnosis and number of catabolic episodes. Sixteen of 21 patients were evaluated cross-sectionally focusing on the neurological and neurocognitive status. Additionally, 155 cases of patients with IVA published in the international literature were reviewed and analyzed for outcome parameters including mortality.Results57% of study patients (12/21) were diagnosed within the first weeks of life and 43% (9/21) in childhood. An acute metabolic attack was the main cause of diagnostic work-up. 44% of investigated study patients (7/16) showed mild motor dysfunction and only 19% (3/16) had cognitive deficits. No other organ complications were found. The patients' intelligence quotient was not related to the number of catabolic episodes but was inversely related to age at diagnosis. In published cases, mortality was high (33%) if associated with neonatal diagnosis, following manifestation at an average age of 7 days.ConclusionsWithin the group of "classical" organic acidurias, IVA appears to be exceptional considering its milder neuropathologic implications. The potential to avoid neonatal mortality and to improve neurologic and cognitive outcome under early treatment reinforces IVA to be qualified for newborn screening.
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Project description:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with an average survival of 3-5 years. While therapies for ALS remain limited, basic and translational ALS research has been host to numerous influential discoveries in recent years. These discoveries have led to a large pipeline of potential therapies that await testing in clinical trials. Until recently, ALS clinical trials have relied on a limited cadre of 'traditional' outcome measures, including survival and measures of function. These measures have proven useful, although imperfect, in Phase III ALS trials. However, their utility in early-phase ALS trials is limited. For these early trials, outcome measures focused on target engagement or biological pathway analysis might improve trial outcomes and better support the drug development process.
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Project description:Breast cancer outcome can be predicted using models derived from gene expression data or clinical data. Only a few studies have created a single prediction model using both gene expression and clinical data. These studies often remain inconclusive regarding an obtained improvement in prediction performance. We rigorously compare three different integration strategies (early, intermediate, and late integration) as well as classifiers employing no integration (only one data type) using five classifiers of varying complexity. We perform our analysis on a set of 295 breast cancer samples, for which gene expression data and an extensive set of clinical parameters are available as well as four breast cancer datasets containing 521 samples that we used as independent validation.mOn the 295 samples, a nearest mean classifier employing a logical OR operation (late integration) on clinical and expression classifiers significantly outperforms all other classifiers. Moreover, regardless of the integration strategy, the nearest mean classifier achieves the best performance. All five classifiers achieve their best performance when integrating clinical and expression data. Repeating the experiments using the 521 samples from the four independent validation datasets also indicated a significant performance improvement when integrating clinical and gene expression data. Whether integration also improves performances on other datasets (e.g. other tumor types) has not been investigated, but seems worthwhile pursuing. Our work suggests that future models for predicting breast cancer outcome should exploit both data types by employing a late OR or intermediate integration strategy based on nearest mean classifiers.
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Project description:BackgroundMastectomy is the first-line treatment approach for more than 90% of breast cancer patients. The numerous physical impairments associated with this surgical procedure negatively impact the patient's quality of life. To date, rehabilitation resources available for breast cancer patients undergoing mastectomy within the institutions affiliated to the Centre intégré universitaire de soins de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec (CIUSSS-MCQ) are lacking and do not always seem to reflect the particularities of breast cancer care pathways. The purpose of this review was to identify and describe the conservative interventions and the clinical outcome measures used in the perioperative physical rehabilitation of women with breast cancer who are awaiting or have undergone mastectomy. We also aimed to report on the barriers and facilitators to study participation and completion.MethodsMEDLINE, CINAHL, and the Cochrane Library were searched from inception to January 2021, and we updated the search on July 11, 2022. We included peer-reviewed English and French literature with quantitative designs, describing conservative interventions and clinical outcome measures used within rehabilitation programs designed for women who were awaiting or had undergone mastectomy. Paired reviewers independently reviewed all citations and articles using a two-phase screening process and independently extracted the data.ResultsOf the 6080 articles identified, 57 met the inclusion criteria. Most interventions were multimodal, which combined exercise with patient education, manual therapy, and/or lymphatic drainage. The most frequently used objective measures of physical function were shoulder range of motion, muscle strength, and signs of lymphedema. In contrast, the primary patient-reported outcome measures were quality of life, shoulder function, and pain. Undergoing another breast surgery, death, and cancer recurrence were the most reported barriers to study completion.ConclusionThis scoping review reports on the heterogeneity and wide range of conservative interventions and clinical outcome measures used in the physical rehabilitation of breast cancer patients who had undergone or were scheduled to undergo mastectomy. Tailoring interventions to breast cancer patients' needs and promoting outpatient rehabilitation interventions appear to be better suited to the particularities of breast cancer care pathways. Further research is needed to better identify barriers and facilitators to study participation and completion.
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Project description:The inositol hexakisphosphate kinase (IP6K) 1 and 2 genes are localized at 3p21.31, a highly altered gene-dense chromosomal region in cancer. The IP6Ks convert IP6 to IP7, which inhibits activation of the tumor-promoting PI3K/Akt/mTOR signaling pathway. IP6K2 has been suggested to be involved in p53-induced apoptosis, while IP6K1 may stimulate tumor growth and migration. The present study aimed to elucidate the role of the two IP6Ks in predicting outcome in patients with breast cancer. To the best of our knowledge, the role of IP6K was analyzed for the first time in tumors from three cohorts of patients with breast cancer; one Swedish low-risk cohort, one Dutch cohort and the TCGA dataset. Analyses of gene -and protein expression and subcellular localization were included. IP6K2 gene expression was associated with ER positivity and nuclear p-Akt. Improved prognosis was detected with high IP6K2 gene expression compared with low IP6K2 gene expression in systemically untreated patients in the Swedish low-risk and Dutch cohorts. In the TCGA dataset, IP6K2 prognostic value was significant when selecting for tumors with wild-type TP53. A multivariable analysis testing IP6K2 against other cancer-related genes at 3p.21.31, including IP6K1 and clinical biomarkers, revealed that IP6K2 was associated with decreased risk of distant recurrence. IP6K1 was associated with increased risk of distant recurrence in the multivariable test and protein analysis revealed trends of worse prognosis with high IP6K1 in the cytoplasm. The expression levels of IP6K1 and IP6K2 were associated to a high extent; however, a diverging prognostic value of the two genes was observed in breast cancer. The present data suggest that IP6K2 can be a favorable prognostic factor, while IP6K1 may not be.
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