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.
During clinical practice, it can be challenging, given the lack of response biomarkers, to identify the patients with metastatic breast cancer (mbca) who would benefit most from the addition of ...bevacizumab to first-line standard chemotherapy. The aim of the present review was to summarize the relevant scientific evidence and to discuss the experience of a group of experts in using bevacizumab to treat mbca.
A panel of 17 Spanish oncology experts met to discuss the literature and their experience in the use of bevacizumab as first-line treatment for mbca. During the meeting, discussions focused on three main issues: the profile of the patients who could benefit most from bevacizumab, the optimal bevacizumab treatment duration, and the safety profile of bevacizumab.
The subset of mbca patients who would benefit the most from the addition of bevacizumab to first-line standard chemotherapy are those with clinically defined aggressive disease. Treatment with bevacizumab should be maintained until disease progression or the appearance of unacceptable toxicity. In the mbca setting, the toxicity profile of bevacizumab is well known and can be managed in clinical practice after adequate training.
This expert group recommends administering bevacizumab as first-line treatment in patients with clinically aggressive disease.
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.
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.
Abstract only
e11581
Background: Preoperative chemotherapy(CT) with trastuzumab(H)improves pathologic complete responses(pCR) in patients(ps)with Her-2+locally advanced breast cancer(LABC). Methods: ...This is an unicenter phaseII trial of a new neoadjuvant CT with H(without anthracyclines)in Her-2+LABC.Primary end-point was pCR.Secondary endpoints were:clinical response rate(CRR);breast conservative surgery rate(BCSR);pathologic tumoral size(pTS);disease-free survival(DFS);overall survival(OS)and toxicity profile.Ps with histologically confirmed Her-2+LABC, PS ≤2, LVEF >50%,and adequate bone marrow, renal and hepatic function were eligible.Treatment:docetaxel(T)36 mg/m
2
IV d1,8 and 22;capecitabine(X)750 mg/m
2
/12h PO d1- 14;and H 4mg/kgIV 1ºd,followed by weekly 2mg/kg in a 4-week course repeated for up to 4cycles,followed by surgery.Ps received a maximum of 6 cycles,according to investigator criteria.Radiotherapy(RT)and hormonetherapy(Ht) were allowed after surgery.Expression of markers was determined by immunohistochemistry(IHC)before CT. Results: The trial was closed due to poor accrual on March 2008.N=16ps:median age=47years(30–68); premenopausal=69%; ductal carcinoma=94%; left side=37,5%; clinical(c)stage:IIA=6.2%,IIB=43.8%;IIIA=31.2%;IIIB=18.8%;c node+=50%; median c tumoral size= 5cm(2- 10);grade:G2=53%and G3=47%;ER+ =75%;PgR+=62.5%;RP+/RE+ =62.5%;EGFR negative =87.5%;p53+=37.5;median KI67=22.5%(2- 79%);Her2+ by IHC+++ =87.5%and IHC++/FISH+ =12.5%;RT= 50%;median dose=50Gy;Ht=75%;and all ps received adjuvant H. 1º End Point: Three ps(18.8%) had pCR in breast and nodes;4ps(25%)had pCR in primary site,and among ps with c node+ 37.5%(3ps)had pCR in nodes. 2º End-Points: 1)CRR=81.2%(complete response=25%;partial=56.2%;no response=18.8%);2)BCSR=6.2%;3)Median pTS=2cm(0–5cm);4)Safety:TXH is very well tolerated:dose delays=14%;dose reductions=7%;no p had a decreased LVEF after neoadjuvant CT.Three ps had decreased LVEF during adjuvant H(median=43%).5)Only 2 events had occurred.Survival data will be reported in the meeting. Conclusions: Neoadjuvant TXH is a new active regimen in Her- 2+LABC with a manageable toxicity profile.
No significant financial relationships to disclose.
The anammox-based process ELAN® was started-up in two different sequencing batch reactor (SBR) pilot plant reactors treating municipal anaerobic digester supernatant. The main difference in the ...operation of both reactors was the dissolved oxygen (DO) concentration in the bulk liquid. SBR-1 was started at a DO value of 0.4 mg O2/L whereas SBR-2 was started at DO values of 3.0 mg O2/L. Despite both reactors working at a nitrogen removal rate of around 0.6 g N/(L d), in SBR-1, granules represented only a small fraction of the total biomass and reached a diameter of 1.1 mm after 7 months of operation, while in SBR-2 the biomass was mainly composed of granules with an average diameter of 3.2 mm after the same operational period. Oxygen microelectrode profiling revealed that granules from SBR-2 where only fully penetrated by oxygen with DO concentrations of 8 mg O2/L while granules from SBR-1 were already oxygen penetrated at DO concentrations of 1 mg O2/L. In this way granules from SBR-2 performed better due to the thick layer of ammonia oxidizing bacteria, which accounted for up to 20% of all the microbial populations, which protected the anammox bacteria from non-suitable liquid media conditions.
Background
Surgical resection with adequate lymphadenectomy is regarded the only curative option for gastric cancer. Regarding minimally invasive techniques, mainly Asian studies showed comparable ...oncological and short-term postoperative outcomes. The incidence of gastric cancer is lower in the Western population and patients often present with more advanced stages of disease. Therefore, the reproducibility of these Asian results in the Western population remains to be investigated.
Methods
A randomized trial was performed in thirteen hospitals in Europe. Patients with an indication for total gastrectomy who received neoadjuvant chemotherapy were eligible for inclusion and randomized between open total gastrectomy (OTG) or minimally invasive total gastrectomy (MITG). Primary outcome was oncological safety, measured as the number of resected lymph nodes and radicality. Secondary outcomes were postoperative complications, recovery and 1-year survival.
Results
Between January 2015 and June 2018, 96 patients were included in this trial. Forty-nine patients were randomized to OTG and 47 to MITG. The mean number of resected lymph nodes was 43.4 ± 17.3 in OTG and 41.7 ± 16.1 in MITG (
p
= 0.612). Forty-eight patients in the OTG group had a R0 resection and 44 patients in the MITG group (
p
= 0.617). One-year survival was 90.4% in OTG and 85.5% in MITG (
p
= 0.701). No significant differences were found regarding postoperative complications and recovery.
Conclusion
These findings provide evidence that MITG after neoadjuvant therapy is not inferior regarding oncological quality of resection in comparison to OTG in Western patients with resectable gastric cancer. In addition, no differences in postoperative complications and recovery were seen.
Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast ...cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC.
One-hundred and ninety patients with stage I-III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m
) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan-Meier method.
Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR HR = 0.30; 95% confidence interval (CI), 0.14-0.62;
= 0.0001. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10-0.63;
= 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS.
Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.
•Fiber laser cladding of Ni-based alloy on cast iron was experimentally studied.•Two different types of cast iron have been analyzed: gray and ductile cast iron.•Suitable processing parameters to ...generate a Ni-based coating were determined.•Dilution is higher in gray cast iron samples than in ductile cast iron.•Ni-based coating presents higher hardness than cast iron but similar Young's modulus.
Gray cast iron is a ferrous alloy characterized by a carbon-rich phase in form of lamellar graphite in an iron matrix while ductile cast iron presents a carbon-rich phase in form of spheroidal graphite. Graphite presents a higher laser beam absorption than iron matrix and its morphology has also a strong influence on thermal conductivity of the material. The laser cladding process of cast iron is complicated by its heterogeneous microstructure which generates non-homogeneous thermal fields. In this research work, a comparison between different types of cast iron substrates (with different graphite morphology) has been carried out to analyze its impact on the process results. A fiber laser was used to generate a NiCrBSi coating over flat substrates of gray cast iron (EN-GJL-250) and nodular cast iron (EN-GJS-400-15). The relationship between processing parameters (laser irradiance and scanning speed) and geometry of a single laser track was examined. Moreover, microstructure and composition were studied by Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDS) and X-Ray Diffraction (XRD). The hardness and elastic modulus were analyzed by means of micro- and nanoindentation. A hardfacing coating was generated by fiber laser cladding. Suitable processing parameters to generate the Ni-based alloy coating were determined. For the same processing parameters, gray cast iron samples present higher dilution than cast iron samples. The elastic modulus is similar for the coating and the substrate, while the Ni-based coating obtained presents a significantly superior hardness than cast iron.
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