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Sökning: WFRF:(Colleoni M)

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  • Geyer, C. E., et al. (författare)
  • Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer
  • 2022
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 33:12, s. 1250-1268
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDES and DDFS with no new safety signals.
  • Pinsky, L., et al. (författare)
  • Measurement of Fragmentation Products including Angular Distributions for 3, 5, and 10 GeV/A C and Si on several nuclear targets at the AGS
  • 2010
  • Ingår i: 2009 12th International Conference on Nuclear Reaction Mechanisms, NRM 2009; Varenna; Italy; 15 June 2009 through 19 June 2009. - 2078-8835. - 9789290833413 ; 2, s. 431-437
  • Konferensbidrag (refereegranskat)abstract
    • Motivated by differences in the predicted fragmentation of heavy ions at energies around 5 GeV/A as employed in the event generators used by the FLUKA Monte Carlo Code [1], a set of measurements were carried out at the AGS facility at the Brookhaven National Laboratory to determine as much information as possible about the cross sections to allow harmonization of those event generators for these incident lab energies. The FLUKA Code employs the RQMD event generator of Sorge [2] for heavy ion interactions starting at 100 MeV/A and extending into the region around 5 GeV/A. Above those energies the DPMJET code of Ranft and Roesler [3] is typically employed to simulate such interactions. The detailed predictions of these event generators had some disagreement in the vicinity of this crossover energy and in order to tune these codes to be in closer harmony at the transition, and of course to be simulating nature as closely as possible, data were taken at 3, 5 and 10 GeV/A with beams of Fe, Si and C on a variety of targets including C, A1. Fe and Cu. The Fe data have not been fully analyzed, but results from the C and Si beams are available and the forward fragment spectrum along with a measurement of the charged particle angular distribution in a set of Si strip detectors out to about 45 degrees in the lab are available. These include sufficient statistics to provide the charged particle distributions as a function of the major projectile fragment. The detectors used in this measurement were based on what were reasonably available to us, and as such were limited in capability, and required separate data acquisition systems. Nevertheless, spectra were obtained that should be sufficient to enable the harmonization of the event generator codes at the crossover energy. This paper discusses only the experimental results and not the impact of those results on the FLUKA code.
  • Battistoni, G, et al. (författare)
  • FLUKA Monte Carlo calculations for hadrontherapy application
  • 2013
  • Ingår i: CERN-Proceedings-2012-002. ; , s. 461-467
  • Konferensbidrag (refereegranskat)abstract
    • Monte Carlo (MC) codes are increasingly spreading in the hadrontherapy community due to their detailed description of radiation transport and interaction with matter. The suitability of a MC code for application to hadrontherapy demands accurate and reliable physical models for the description of the transport and the interaction of all components of the expected radiation field (ions, hadrons, electrons, positrons and photons). This contribution will address the specific case of the general-purpose particle and interaction code FLUKA. In this work, an application of FLUKA will be presented, i.e. establishing CT (computed tomography)-based calculations of physical and RBE (relative biological effectiveness)-weighted dose distributions in scanned carbon ion beam therapy.
  • Battistoni, G., et al. (författare)
  • The FLUKA code and its use in hadron therapy
  • 2008
  • Ingår i: Nuovo Cimento della Societa Italiana di Fisica C. - Italian Physical Society. - 1124-1896. ; 31:1, s. 69-75
  • Tidskriftsartikel (refereegranskat)abstract
    • FLUKA is a multipurpose Monte Carto code describing transport and interaction with matter of a, large variety of particles over a wide energy range ill complex geometries. FLUKA is successfully applied ill several fields, including, but not only particle physics, cosmic-ray physics, dosimetry, radioprotection, hadron therapy. space radiation, accelerator design and neutronics. Here we briefly review recent model developments and provide examples of applications to hadron therapy, including calculation of physical and biological dose for comparison with analytical treatment planning engines as well as beta(+)-activation for therapy monitoring by means of positron emission tomography.
  • Curigliano, G, et al. (författare)
  • De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.
  • 2017
  • Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 28:8, s. 1700-1712
  • Tidskriftsartikel (refereegranskat)abstract
    • The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.
  • Jerusalem, G, et al. (författare)
  • Continuous versus intermittent extended adjuvant letrozole for breast cancer: Final results of randomized phase 3 SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy.
  • 2021
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 32:10, s. 1256-1266
  • Tidskriftsartikel (refereegranskat)abstract
    • Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in extended endocrine therapy. In animal models, resistance was reversed with restoration of circulating estrogen level during interruption of letrozole treatment. This phase 3 randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen sub-study (SOLE-EST) analyzed the level of estrogen during the interruption of treatment.SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant endocrine therapy. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all year 5).Intention-to-treat population included 4851 women in SOLE (n=2425 in intermittent and n=2426 in continuous letrozole groups) and 103 women in SOLE-EST (n=78 in intermittent and n=25 in continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival was 81.4% in intermittent group and 81.5% in continuous group (hazard ratio: 1.03, 95%CI: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment.Extended adjuvant endocrine therapy by intermittent administration of letrozole did not improve disease-free survival compared to continuous use despite the recovery of circulating estrogen level. The similar disease-free survival coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.
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  • Resultat 1-10 av 25
  • [1]23Nästa

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