Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study

Càncer de coll uterí; Platí; TopotecanCáncer de cuello uterino; Platino; TopotecanCervical cancer; Platinum; TopotecanObjective To determine whether a non‑platinum chemotherapy doublet improves overall survival (OS) among patients with recurrent/metastatic cervical carcinoma. Methods Gynecologic Oncology Group protocol 240 is a phase 3, randomized, open-label, clinical trial that studied the efficacy of paclitaxel 175 mg/m2 plus topotecan 0.75 mg/m2 days 1–3 (n = 223) vs cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2 (n = 229), in 452 patients with recurrent/metastatic cervical cancer. Each chemotherapy doublet was also studied with and without bevacizumab (15 mg/kg). Cycles were repeated every 21 days until progression, unacceptable toxicity, or complete response. The primary endpoints were OS and the frequency and severity of adverse effects. We report the final analysis of OS. Results At the protocol-specified final analysis, median OS was 16.3 (cisplatin-paclitaxel backbone) and 13.8 months (topotecan-paclitaxel backbone) (HR 1.12; 95% CI, 0.91–1.38; p = 0.28). Median OS for cisplatin-paclitaxel and topotecan-paclitaxel was 15 vs 12 months, respectively (HR 1.10; 95% CI,0.82–1.48; p = 0.52), and for cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab was 17.5 vs 16.2 months, respectively (HR 1.16; 95% CI, 0.86–1.56; p = 0.34). Among the 75% of patients in the study population previously exposed to platinum, median OS was 14.6 (cisplatin-paclitaxel backbone) vs 12.9 months (topotecan-paclitaxel backbone), respectively (HR 1.09; 95% CI, 0.86–1.38;p = 0.48). Post-progression survival was 7.9 (cisplatin-paclitaxel backbone) vs 8.1 months (topotecan-paclitaxel backbone) (HR 0.95; 95% CI, 0.75–1.19). Grade 4 hematologic toxicity was similar between chemotherapy backbones. Conclusions Topotecan plus paclitaxel does not confer a survival benefit to women with recurrent/metastatic cervical cancer, even among platinum-exposed patients. Topotecan-paclitaxel should not be routinely recommended in this population.This study was supported by the following National Cancer Institute and Genentech grants: NRG Oncology (1U10CA180822), NRG Operations (U10CA180868) and NCORP grant UG1CA189867

Radiative Corrections to Electron-Proton Scattering

The radiative corrections to elastic electron-proton scattering are analyzed in a hadronic model including the finite size of the nucleon. For initial electron energies above 8 GeV and large scattering angles, the proton vertex correction in this model increases by at least two percent the overall factor by which the one-photon exchange (Rosenbluth) cross section must be multiplied. The contribution of soft photon emission is calculated exactly. Comparison is made with the generally used expressions previously obtained by Mo and Tsai. Results are presented for some kinematics at high momentum transfer.Comment: 31 pages, 4 figure

Effect of recent R_p and R_n measurements on extended Gari-Krumpelmann model fits to nucleon electromagnetic form factors

The Gari-Krumpelmann (GK) models of nucleon electromagnetic form factors, in which the rho, omega, and phi vector meson pole contributions evolve at high momentum transfer to conform to the predictions of perturbative QCD (pQCD), was recently extended to include the width of the rho meson by substituting the result of dispersion relations for the pole and the addition of rho' (1450) isovector vector meson pole. This extended model was shown to produce a good overall fit to all the available nucleon electromagnetic form factor (emff) data. Since then new polarization data shows that the electric to magnetic ratios R_p and R_n obtained are not consistent with the older G_{Ep} and G_{En} data in their range of momentum transfer. The model is further extended to include the omega' (1419) isoscalar vector meson pole. It is found that while this GKex cannot simultaneously fit the new R_p and the old G_{En} data, it can fit the new R_p and R_n well simultaneously. An excellent fit to all the remaining data is obtained when the inconsistent G_{Ep} and G_{En} is omitted. The model predictions are shown up to momentum transfer squared, Q^2, of 8 GeV^2/c^2.Comment: 14 pages, 8 figures, using RevTeX4; email correspondence to [email protected] ; minor typos corrected, figures added, conclusions extende

Extended Gari-Krumpelmann model fits to nucleon electromagnetic form factors

Nucleon electromagnetic form factor data (including recent data) is fitted with models that respect the confinement and asymptotic freedom properties of QCD. Gari-Krumpelmann (GK) type models, which include the major vector meson pole contributions and at high momentum transfer conform to the predictions of perturbative QCD, are combined with Hohler-Pietarinen (HP) models, which also include the width of the rho meson and the addition of higher mass vector meson exchanges, but do not evolve into the explicit form of PQCD at high momentum transfer. Different parameterizations of the GK model's hadronic form factors, the effect of including the width of the rho meson and the addition of the next (in mass) isospin 1 vector meson are considered. The quality of fit and the consistency of the parameters select three of the combined HP/GK type models. Projections are made to the higher momentum transfers which are relevant to electron-deuteron experiments. The projections vary little for the preferred models, removing much of the ambiguity in electron-nucleus scattering predictions.Comment: 18pp, 7 figures, using RevTeX with BoxedEPS macros; 1 new figure, minor textual changes; email correspondence to [email protected]

Anchoring Bias in Online Voting

Voting online with explicit ratings could largely reflect people's preferences and objects' qualities, but ratings are always irrational, because they may be affected by many unpredictable factors like mood, weather, as well as other people's votes. By analyzing two real systems, this paper reveals a systematic bias embedding in the individual decision-making processes, namely people tend to give a low rating after a low rating, as well as a high rating following a high rating. This so-called \emph{anchoring bias} is validated via extensive comparisons with null models, and numerically speaking, the extent of bias decays with interval voting number in a logarithmic form. Our findings could be applied in the design of recommender systems and considered as important complementary materials to previous knowledge about anchoring effects on financial trades, performance judgements, auctions, and so on.Comment: 5 pages, 4 tables, 5 figure

Octet-Baryon Form Factors in the Diquark Model

We present an alternative parameterization of the quark-diquark model of baryons which particularly takes care of the most recent proton electric form-factor data from the E136 experiment at SLAC. In addition to electromagnetic form factors of the nucleon, for which good agreement with data is achieved, we discuss the weak axial vector form factor of the nucleon as well as electromagnetic form factors of $\Lambda$ and $\Sigma$ hyperons. Technical advance in calculating the pertinent analytic expressions within perturbative quantum chromodynamics is gained by formulating the wave function of the quark-diquark system in a covariant way. Finally, we also comment on the influence of Sudakov corrections within the scope of the diquark model.Comment: 16 pages, WU-B 93-07, latex, uuencoded postscript files of 7 figures appended at the end of the latex fil

Electro-Magnetic Nucleon Form Factors and their Spectral Functions in Soliton Models

It is demonstrated that in simple soliton models essential features of the electro-magnetic nucleon form factors observed over three orders of magnitude in momentum transfer $t$ are naturally reproduced. The analysis shows that three basic ingredients are required: an extended object, partial coupling to vector mesons, and relativistic recoil corrections. We use for the extended object the standard skyrmion, one vector meson propagator for both isospin channels, and the relativistic boost to the Breit frame. Continuation to timelike $t$ leads to quite stable results for the spectral functions in the regime from the 2- or 3-pion threshold to about two rho masses. Especially the onset of the continuous part of the spectral functions at threshold can be reliably determined and there are strong analogies to the results imposed on dispersion theoretic approaches by the unitarity constraint.Comment: 24 pages, (RevTeX), 5 PS-figures; Data points in fig.2 and corresponding references added. Final version, to be published in Z.Physik

Prospective Validation of Pooled Prognostic Factors in Women with Advanced Cervical Cancer Treated with Chemotherapy with/without Bevacizumab: NRG Oncology/GOG Study

PURPOSE: In the randomized phase III trial, Gynecologic Oncology Group (GOG) protocol 240, the incorporation of bevacizumab with chemotherapy significantly increased overall survival (OS) in women with advanced cervical cancer. A major objective of GOG-240 was to prospectively analyze previously identified pooled clinical prognostic factors known as the Moore criteria. EXPERIMENTAL DESIGN: Potential negative factors included black race, performance status 1, pelvic disease, prior cisplatin, and progression-free interval <365 days. Risk categories included low-risk (0-1 factor), mid-risk (2-3 factors), and high-risk (4-5 factors). Each test of association was conducted at the 5% level of significance. Logistic regression and survival analysis was used to determine whether factors were prognostic or could be used to guide therapy. RESULTS: For the entire population (n = 452), high-risk patients had significantly worse OS (P < 0.0001). The HRs of death for treating with topotecan in low-risk, mid-risk, and high-risk subsets are 1.18 [95% confidence interval (CI), 0.63-2.24], 1.11 (95% CI, 0.82-1.5), and 0.84 (95% CI, 0.50-1.42), respectively. The HRs of death for treating with bevacizumab in low-risk, mid-risk, and high-risk subsets are 0.96 (95% CI, 0.51-1.83; P = 0.9087), 0.673 (95% CI, 0.5-0.91; P = 0.0094), and 0.536 (95% CI, 0.32-0.905; P = 0.0196), respectively. CONCLUSIONS: This is the first prospectively validated scoring system in cervical cancer. The Moore criteria have real-world clinical applicability. Toxicity concerns may justify omission of bevacizumab in some low-risk patients where survival benefit is small. The benefit to receiving bevacizumab appears to be greatest in the moderate- and high-risk subgroups (5.8-month increase in median OS)

(EIN)FACH? : Komplexität, Wissen, Fortschritt und die Grenzen der Germanistik

Spätestens seit den gesellschaftlichen Modernisierungsschüben in den sechziger Jahren identifiziert auch die Germanistik Erkenntnis- und Wissenszuwachs, ja allgemeiner den "Fortschritt" ihres Fachs, mit Komplexitätserhöhung. Vor diesem Hintergrund erscheint es mir wenig plausibel, die seitdem erfolgten inneren Ausdifferenzierungen und interdisziplinären Grenzüberschreitungen als durch Identitätsverlust, Zerstreuung und Desintegration gekennzeichnete Niedergangsszenarien zu beschreiben. Die Veränderungen gehorchen der immanenten Logik germanistischer Forschung, einer "disziplinierten", auf Leistung ausgerichteten, an kooperativen Großforschungsvorhaben partizipierenden Wissensproduktion