Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript ...quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular.
The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80.
In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Persistent alopecia (PA) after docetaxel has been recently described. The aim of our study is to establish the incidence and characteristics of PA following adjuvant docetaxel for breast ...cancer (BC) and to test the ability of scalp cooling in prevention.
Patients and methods
BC patients receiving adjuvant chemotherapy followed or not by endocrine therapy (and a control group receiving only endocrine therapy) were interviewed in a single institution at 1.5 to 5 years following primary diagnosis searching for PA. A confirmatory prevalence study was later performed in other two institutions. Finally, a prevention study using prophylactic scalp cooling (PSC) with ELASTO-GEL hypothermia caps in patients receiving adjuvant docetaxel was performed.
Results
In the initial prevalence study (492 patients), minor forms of PA (grade 1) were recorded with all chemotherapy regimens and aromatase inhibitors. Patients receiving docetaxel regimens at cumulative dose (CD) ≥ 400 mmg/m
2
presented a significantly higher prevalence of grades 1 PA (33–52%) and 2 PA (5–12%). Prevalence of grade 2 PA with docetaxel CD ≥ 400 mmg/m
2
was confirmed in two other institutions. Overall, grade 2 PA was seen in 10.06% (95% CI 7.36–13.61) of 358 patients with docetaxel regimens reaching CD ≥ 400 mmg/m
2
, but not in patients with lower docetaxel CD, other chemotherapy regimens, or endocrine therapy alone. In prevention trial, no grade 2 PA occurred among 116 patients receiving adjuvant docetaxel (≥ 400 mmg/m
2
) and PSC followed-up after a 96 months median time. PSC was well tolerated. No scalp relapses were seen among 30 patients (22% of all inclusions) having disease relapse.
Conclusion
Adjuvant treatment with docetaxel (CD ≥ 400 mmg/m
2
) is associated with a significant rate of grade 2 PA, leading to wearing a wig, in around 10% of patients. This toxicity was completely prevented with scalp cooling. Clinical Trial Reference: NCT00515762.
In the original publication of the article, Table 1 was published with incorrect caption and values. The Table 1 with corrected caption and values is given in this Correction.
Background and ImportanceClinical trials are the main source of information to establish new treatments’ efficacy and safety. Patients’ enrolment in these studies may result in economic benefits for ...the participating sites since usually the costs derived from their inclusion are funded by sponsors. However, these economic benefits are rarely quantified.Aim and ObjectivesThe primary object of this study was to calculate the economic benefit obtained from patients’ inclusion in lung cancer clinical trials in two scopes: medication and medical tests. The secondary object was to determine whether avoided costs in medication were significantly different from those in medical tests.Material and MethodsAn observational retrospective study was conducted in all patients enrolled in lung cancer clinical trials from 2017 to 2021 at our hospital.The avoided costs in medication were calculated considering the medication which would have been given to the patient in the standard of care taking into account their specific data.The avoided costs in medical tests per patient were calculated from the prices published and the total number of each test performed on each patient from their first treatment visit until the end of the treatment visit.The homogeneity of the two groups was analysed using a univariate analysis by applying the chi-square test for qualitative variables and the t test or Mann-Whitney test to compare quantitative variables. A p value of <0.05 was considered statistically significant.ResultsThe economic benefit generated from sponsor-provided drugs in the 35 clinical trials was 3,778,393.93€.A total of 642 medical tests were performed in the 117 patients under study. Specifically, 546 were CTs, 58 were MRs, 6 PETs and 32 were gamma graphics. The total economic benefit generated in five years by the sponsor financing these tests was 128,448€.The results from the statistical analysis revealed that the economic differences between sponsors providing the medication and financing the medical tests were significantly different with p<0.05 (p=0.0482).Conclusion and RelevanceIn the 5 years studied, over 3.9 million euros were saved by including patients in lung cancer trials in one site, being 96.7% derived from avoided costs in medication. Thus, the participation of patients in clinical trials is economically beneficial for them and society.References and/or AcknowledgementsConflict of InterestNo conflict of interest.
Abstract
SUMMARY: Over the past two decades significant progress has been made in breast cancer treatment resulting in a substantial improvement in patients' outcome. But we have to think about who ...promotes all this research and the consequences of the type of fundingThis project aims to evaluate the implication of finance in clinical research and the variance according to the type of funding.
OBJETIVES: To evaluate the financial evolvement of breast cancer clinical trials in the past two decades, regarding the phase of development design of the studies, the collaboration between Academy (Acad) and Industry (Ind), the sample size, the study results and the statistical analyses conducted.
METHODS: A systematic review was performed using MEDLINE to identify breast cancer randomized clinical trials published between January1990 and December2010. Studies that involved chemotherapy, endocrine and/or targeted therapies, wherethe primary endpoint was considered adequate to support a drug approval in oncology according to the FDA and EMA (U.S. Food and Drug Administration and European Medicines Agency, respectively), were included.
RESULTS:Data were evaluated 2,211 and 472 met selection criteria comprised in the methodology During the first decade the Acad was the main breast cancer research promoter being replaced by the Inv. throughout the second decade (p <0.0001). Thirty nine percent of the studies evaluated were phase III (39% Acad, 61% Ind), 15% were phase II (30% Acad, 70% Ind) and the remaining 47% were not classified by authors (65% Acad 35% Ind). As for the primary endpoint, 25% of the phase III trials evaluated progression free survival, 15% overall response rate, 1% time to progression and only 5% examined overall survival. Sixty five percent of the trials were national (60% Acad 40% Ind) and 35% international (25% Acad 75% Ind). Single-center studies accounted for 11% of the trial (65% Acad 35% Ind). Most of the national trials were developed by the US. Fifty four percent of the studies were conducted by research groups (67% supported by Ind. and 33% Acad.). The Ind sponsored 26% of the studies in the first decade and 50% during the second. The median number of patients enrolled by research groups was 892 in contrast with 409 included by other organizations. The primary endpoint was achieved in 19% of the Acad trials and 21% of the Ind trials. Only 53% of the studies declared intention to treat based analysis in their statistical workout.
RESULTS ACADEMY(%)INDUSTRY (%)PPROMOTION OF THE STUDY1990-2000121(26)68(14)0,0001 2001-2010105(22)178(38)0,0001STUDY DESIGNUNICENTRIC TRIALS34(7)18(4)0,007 MULTICENTRIC TRIALS191(40)228(48) NATIONAL TRIALS183(39)122(26)0,0001 INTERNATIONAL TRIALS42(9)124(26) COOPERATIVE GROUP95(20)160(34) NOT COOPERATIVE GROUP130(28)86(18) STATISTICAL ANALYSISINTENT OF TREAT86(18)163(35) NOT DECLARATED140(30)83(18)
CONCLUSIONS:There is a significant tendency towards the promotion of research by the pharmaceutical industries during the last two decades, leading a change in the clinical trials design and the endpoints.
Citation Format: Jerez Y, Lopez-Tarruella S, Marquez-Rodas I, Perez S, Ocaña A, Echavarria I, Lobo M, Gallego I, Torres G, Ortega L, Garcia G, Palomero I, Gonzalez Del Val R, Massarrah T, Esteban M, Del Monte-Millan M, Martin M. Implications of financial modeling in breast cancer clinical research from 1990 to 2010 abstract. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-20-01.
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