This randomized study was designed to investigate the superiority of gemcitabine (gem) plus nimotuzumab (nimo), an anti-epidermal growth factor receptor monoclonal antibody, compared with gem plus ...placebo as first-line therapy in patients with advanced pancreatic cancer.
Patients with previously untreated, unresectable, locally advanced or metastatic pancreatic cancer were randomly assigned to receive gem: 1000 mg/m2, 30-min i.v. once weekly (d1, 8, 15; q29) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or gem plus placebo, until progression or unacceptable toxicity. The primary end point was overall survival (OS), secondary end points included time to progression, overall response rate, safety and quality of life.
A total of 192 patients were randomized, with 186 of them being assessable for efficacy and safety (average age 63.6 years). One-year OS/progression-free survival (PFS) was 34%/22% for gem plus nimo compared with 19%/10% for gem plus placebo (HR = 0.69; P = 0.03/HR = 0.68; P = 0.02). Median OS/PFS was 8.6/5.1 months for gem plus nimo versus 6.0/3.4 mo in the gem plus placebo group (HR = 0.69; P = 0.0341/HR = 0.68; P = 0.0163), with very few grade 3/4 toxicities. KRAS wildtype patients experienced a significantly better OS than those with KRAS mutations (11.6 versus 5.6 months, P = 0.03).
This randomized study showed that nimo in combination with gem is safe and well tolerated. The 1-year OS and PFS rates for the entire population were significantly improved. Especially, those patients with KRAS wildtype seem to benefit. The study was registered as protocol ID OSAG101-PCS07, NCT00561990 and EudraCT 2007-000338-38.
The SXP instrument at the European XFEL Grychtol, P.; Kohlstrunk, N.; Buck, J. ...
Journal of physics. Conference series,
12/2022, Letnik:
2380, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
The successful implementation of the baseline instruments at the European XFEL has triggered a second phase of instrument developments aiming to extend the portfolio of available techniques. ...At the soft X-ray undulator (SASE 3), the Soft X-ray Port (SXP) instrument is currently under construction. Conceived as an open port, it focuses primarily on femtosecond time-resolved X-ray photoelectron spectroscopy (TR-XPES), which has proven to be a powerful tool to understand the properties of materials and the interaction between their internal degrees of freedom. The extension of this technique to the soft X-ray energy range is only possible at MHz free electron lasers (FELs) due to space-charge effects which limit the maximum photon flux per pulse on the sample. In this contribution, the SXP instrument at the European XFEL and the implementation of TR-XPES using a momentum microscope are presented. The photon energy range available at SASE 3, 0.25 keV to 3.5 keV, and the variable polarization will allow for the simultaneous characterization of the electronic, magnetic, chemical and structural properties of materials with femtosecond time resolution. To this end, a wide range of laser excitation wavelengths, ranging from the XUV to the THz region, will be available.
The SASE1 X‐ray beam transport system Sinn, H.; Dommach, M.; Dickert, B. ...
Journal of synchrotron radiation,
20/May , Letnik:
26, Številka:
3
Journal Article
Recenzirano
SASE1 is the first beamline of the European XFEL that became operational in 2017. It consists of the SASE1 undulator system, the beam transport system, and the two scientific experiment stations: ...Single Particles, Clusters, and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX), and Femtosecond X‐ray Experiments (FXE). The beam transport system comprises mirrors to offset and guide the beam to the instruments and a set of X‐ray optical components to align, manipulate and diagnose the beam. The SASE1 beam transport system is described here in its initial configuration, and results and experiences from the first year of user operation are reported.
The beam transport system of the European XFEL SASE1 beamline is described together with experiences gained during the first user runs.
Background
An earlier published series of neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. ...Long-term outcome data and predictive factors for pathologic complete response (pCR) were analyzed.
Patients and methods
During 1991–1998, 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or—in case of breast conservation—a 10-Gy interstitial boost with
192
Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow-up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX, and the time interval between end of RT and surgery were examined in multivariate terms with pCR and overall survival as end point.
Results
The total pCR rate after neoadjuvant RT-CHX reached 29.2%, with LABC breast conservation becoming possible in 50.8% of cases. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1.17 95% CI 1.05–1.31, p < 0.01). However, in large tumors (T3–T4) a significantly reduced pCR rate (HR 0.89 95% CI 0.80–0.99, p = 0.03) was obtained. Importantly, pCR was the strongest prognostic factor for long-term survival (HR 0.28 95% CI 0.19–0.56, p < 0.001).
Conclusion
pCR identifies patients with a significantly better prognosis for long-term survival. However, a long time interval to surgery (> 2 months) increases the probability of pCR after NRT-CHX.
Uniaxially oriented polypropylene (PP) is molten in the synchrotron beam and crystallized from the quiescent melt, keeping its orientation in order to study the mechanisms of its crystallization. We ...document the different nanostructures observed as a function of melt-annealing temperature, undercooling, and time. In order to obtain a melt that crystallizes with high preferential orientation again, a melt-annealing temperature between 170 and 176 °C is chosen. Isothermal crystallization at 155 °C results in slow formation of (primary) lamellae placed at random. As the crystallization temperature is decreased (150, 145, and 140 °C), more and more secondary crystallites are observed which develop from a block mesostructure according to Strobl's mechanism. During the isothermal phase the blocks are fusing more or less to form imperfect lamellae. The structure evolution observed in the time-resolved small-angle X-ray scattering (SAXS) data during crystallization and remelting facilitates discrimination between the block structure and another frequently discussed morphology, Keller's cross-hatched structure. While after all our quiescent crystallization experiments most of the crystallites are blocks or incompletely fused lamellae, the hard-elastic precursor material which has been made under extreme gradients of temperature and pressure exhibits the melting of homogeneous and extended lamellae. As we apply a steep temperature gradient (−100 °C/min) to our melt in a nonisothermal crystallization experiment, we initially observe the formation of homogeneous and extended lamellae as well.
An earlier published series of neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. Long-term ...outcome data and predictive factors for pathologic complete response (pCR) were analyzed. During 1991-1998, 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5×2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or--in case of breast conservation--a 10-Gy interstitial boost with ^sup 192^Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow-up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX, and the time interval between end of RT and surgery were examined in multivariate terms with pCR and overall survival as end point. The total pCR rate after neoadjuvant RT-CHX reached 29.2%, with LABC breast conservation becoming possible in 50.8% of cases. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1.17 95% CI 1.05-1.31, p<0.01). However, in large tumors (T3-T4) a significantly reduced pCR rate (HR 0.89 95% CI 0.80-0.99, p=0.03) was obtained. Importantly, pCR was the strongest prognostic factor for long-term survival (HR 0.28 95% CI 0.19-0.56, p<0.001). pCR identifies patients with a significantly better prognosis for long-term survival. However, a long time interval to surgery (>2 months) increases the probability of pCR after NRT-CHX.PUBLICATION ABSTRACT
This randomized study was designed to investigate the superiority of gemcitabine (gem) plus nimotuzumab (nimo), an anti-epidermal growth factor receptor monoclonal antibody, compared with gem plus ...placebo as first-line therapy in patients with advanced pancreatic cancer.
Patients with previously untreated, unresectable, locally advanced or metastatic pancreatic cancer were randomly assigned to receive gem: 1000 mg/m2, 30-min i.v. once weekly (d1, 8, 15; q29) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or gem plus placebo, until progression or unacceptable toxicity. The primary end point was overall survival (OS), secondary end points included time to progression, overall response rate, safety and quality of life.
A total of 192 patients were randomized, with 186 of them being assessable for efficacy and safety (average age 63.6 years). One-year OS/progression-free survival (PFS) was 34%/22% for gem plus nimo compared with 19%/10% for gem plus placebo (HR = 0.69;P = 0.03/HR = 0.68;P = 0.02). Median OS/PFS was 8.6/5.1 months for gem plus nimo versus 6.0/3.4 mo in the gem plus placebo group (HR = 0.69;P = 0.0341/HR = 0.68;P = 0.0163), with very few grade 3/4 toxicities.KRAS wildtype patients experienced a significantly better OS than those withKRAS mutations (11.6 versus 5.6 months,P = 0.03).
This randomized study showed that nimo in combination with gem is safe and well tolerated. The 1-year OS and PFS rates for the entire population were significantly improved. Especially, those patients withKRAS wildtype seem to benefit.
The study was registered as protocol ID OSAG101-PCS07, NCT00561990 and EudraCT 2007-000338-38.
The isothermal amorphous to smectic phase transformation of a polybibenzoate was investigated by simultaneous medium- and wide-angle X-ray scattering (MAXS and WAXS) and dielectric spectroscopy (DS). ...By this experimental approach, simultaneously collected information was obtained about the specific changes occurring in both amorphous and smectic phases during the transformation. The main experimental features can be explained assuming a transformation mechanism involving the initial growth of smectic domains, during a primary time period, and the improvement of order in the smectic domains during a secondary time regime.
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