256 research outputs found

    Development and Validation of Nomograms Predictive of Overall and Progression-Free Survival in Patients With Oropharyngeal Cancer

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    Purpose Treatment of oropharyngeal squamous cell carcinoma (OPSCC) is evolving toward risk-based modification of therapeutic intensity, which requires patient-specific estimates of overall survival (OS) and progression-free survival (PFS). Methods To develop and validate nomograms for OS and PFS, we used a derivation cohort of 493 patients with OPSCC with known p16 tumor status (surrogate of human papillomavirus) and cigarette smoking history (pack-years) randomly assigned to clinical trials using platinum-based chemoradiotherapy (NRG Oncology Radiation Therapy Oncology Group [RTOG] 0129 and 0522). Nomograms were created from Cox models and internally validated by use of bootstrap and cross-validation. Model discrimination was measured by calibration plots and the concordance index. Nomograms were externally validated in a cohort of 153 patients with OPSCC randomly assigned to a third trial, NRG Oncology RTOG 9003. Results Both models included age, Zubrod performance status, pack-years, education, p16 status, and T and N stage; the OS model also included anemia and age × pack-years interaction; and the PFS model also included marital status, weight loss, and p16 × Zubrod interaction. Predictions correlated well with observed 2-year and 5-year outcomes. The uncorrected concordance index was 0.76 (95% CI, 0.72 to 0.80) for OS and 0.70 (95% CI, 0.66 to 0.74) for PFS, and bias-corrected indices were similar. In the validation set, OS and PFS models were well calibrated, and OS and PFS were significantly different across tertiles of nomogram scores (log-rank P = .003;\u3c .001). Conclusion The validated nomograms provided useful prediction of OS and PFS for patients with OPSCC treated with primary radiation-based therapy

    A Prospective Study to Validate the Functional Assessment of Cancer Therapy (FACT) for Epidermal Growth Factor Receptor Inhibitor (EGFRI)-induced Dermatologic Toxicities FACT-EGFRI 18 Questionnaire: SWOG S1013

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    Background Papulopustular rash is a common class effect of epidermal growth factor receptor inhibitors (EGFRI) that can affect patients’ health-related quality of life and cause disruptions to treatment. SWOG S1013 (NCT01416688) is a multi-center study designed to validate the Functional Assessment of Cancer Therapy EGFRI 18 (FACT-EGFRI 18) using 7-items from the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 to assess EGFRI-induced skin-related toxicities and their impact on functional status. Methods Patients with a diagnosis of colorectal or lung cancer to receive EGFRI therapies for at least 6 weeks were enrolled. Patient self-assessments using the FACT-EGFRI 18 were completed prior to undergoing CTCAE assessment by trained clinicians at baseline, weekly × 6, and then monthly × 3. The psychometric properties of the FACT-EGFRI 14 (skin toxicity items only) and 18 (plus 2 nail and 2 hair items) were established based on criterion validity, known groups validity, internal consistency reliability, and responsiveness to change. Results Of the 146 registered patients, 124 were evaluable. High Cronbach’s alpha (\u3e 0.70) for both FACT-EGFRI 14 and FACT-EGFRI 18 scores across assessment times were observed. Although agreement (i.e. criterion validity) between individual and summary scales of the FACT-EGFRI 18 for assessing skin toxicity was good, agreement with the clinician-reported CTCAE was only fair. The minimal important difference was determined to be 3 points. The results also demonstrated responsiveness to symptom change. Discussion Based on the results of this multi-center validation study, the FACT-EGFRI 18 patient-reported outcome instrument provided data from the patient’s perspective yielding unique information as well as complementing clinician-rated CTCAE grades, especially for the symptoms of pain, pruritus, and paronychia. Conclusions Good to excellent psychometric properties for the FACT-EGFRI 18 were demonstrated, supporting further use of this patient-reported outcomes measure. Additional validation with a more diverse group of patients should be conducted

    Long-Term Follow-Up of Cardiac Function and Quality of Life for Patients in NSABP Protocol B-31/NRG Oncology: A Randomized Trial Comparing the Safety and Efficacy of Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel With AC Followed by Paclitaxel and Trastuzumab in Patients With Node-Positive Breast Cancer With Tumors Overexpressing Human Epidermal Growth Factor Receptor 2

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    Purpose Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment. Patients and Methods Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2–positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported outcomes using the Duke Activity Status Index (DASI), the Medical Outcomes Study questionnaire, and a review of current medications and comorbid conditions. Results At a median follow-up of 8.8 years among eligible participants, five (4.5%) of 110 in the control group and 10 (3.4%) of 297 in the trastuzumab group had a \u3e 10% decline in left ventricular ejection fraction from baseline to a value \u3c 50%. Lower DASI scores correlated with age and use of medications for hypertension, cardiac conditions, diabetes, and hyperlipidemia, but not with whether patients had received trastuzumab. Conclusion In patients without underlying cardiac disease at baseline, the addition of trastuzumab to adjuvant anthracycline and taxane-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or health-related quality of life. The DASI questionnaire may provide a simple and useful tool for monitoring patient-reported changes that reflect cardiac function

    Planck 2013 results. XXII. Constraints on inflation

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    We analyse the implications of the Planck data for cosmic inflation. The Planck nominal mission temperature anisotropy measurements, combined with the WMAP large-angle polarization, constrain the scalar spectral index to be ns = 0:9603 _ 0:0073, ruling out exact scale invariance at over 5_: Planck establishes an upper bound on the tensor-to-scalar ratio of r < 0:11 (95% CL). The Planck data thus shrink the space of allowed standard inflationary models, preferring potentials with V00 < 0. Exponential potential models, the simplest hybrid inflationary models, and monomial potential models of degree n _ 2 do not provide a good fit to the data. Planck does not find statistically significant running of the scalar spectral index, obtaining dns=dln k = 0:0134 _ 0:0090. We verify these conclusions through a numerical analysis, which makes no slowroll approximation, and carry out a Bayesian parameter estimation and model-selection analysis for a number of inflationary models including monomial, natural, and hilltop potentials. For each model, we present the Planck constraints on the parameters of the potential and explore several possibilities for the post-inflationary entropy generation epoch, thus obtaining nontrivial data-driven constraints. We also present a direct reconstruction of the observable range of the inflaton potential. Unless a quartic term is allowed in the potential, we find results consistent with second-order slow-roll predictions. We also investigate whether the primordial power spectrum contains any features. We find that models with a parameterized oscillatory feature improve the fit by __2 e_ _ 10; however, Bayesian evidence does not prefer these models. We constrain several single-field inflation models with generalized Lagrangians by combining power spectrum data with Planck bounds on fNL. Planck constrains with unprecedented accuracy the amplitude and possible correlation (with the adiabatic mode) of non-decaying isocurvature fluctuations. The fractional primordial contributions of cold dark matter (CDM) isocurvature modes of the types expected in the curvaton and axion scenarios have upper bounds of 0.25% and 3.9% (95% CL), respectively. In models with arbitrarily correlated CDM or neutrino isocurvature modes, an anticorrelated isocurvature component can improve the _2 e_ by approximately 4 as a result of slightly lowering the theoretical prediction for the ` <_ 40 multipoles relative to the higher multipoles. Nonetheless, the data are consistent with adiabatic initial conditions

    Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

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    Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

    Planck 2013 results. III. LFI systematic uncertainties

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    We present the current estimate of instrumental and systematic effect uncertainties for the Planck-Low Frequency Instrument relevant to the first release of the Planck cosmological results. We give an overview of the main effects and of the tools and methods applied to assess residuals in maps and power spectra. We also present an overall budget of known systematic effect uncertainties, which are dominated sidelobe straylight pick-up and imperfect calibration. However, even these two effects are at least two orders of magnitude weaker than the cosmic microwave background (CMB) fluctuations as measured in terms of the angular temperature power spectrum. A residual signal above the noise level is present in the multipole range <20\ell<20, most notably at 30 GHz, and is likely caused by residual Galactic straylight contamination. Current analysis aims to further reduce the level of spurious signals in the data and to improve the systematic effects modelling, in particular with respect to straylight and calibration uncertainties.Comment: Accepted for publication by A&

    Planck 2015 results. V. LFI calibration

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    We present a description of the pipeline used to calibrate the Planck Low Frequency Instrument (LFI) timelines into thermodynamic temperatures for the Planck 2015 data release, covering four years of uninterrupted operations. As in the 2013 data release, our calibrator is provided by the spin-synchronous modulation of the cosmic microwave background dipole, but we now use the orbital component, rather than adopting the Wilkinson Microwave Anisotropy Probe (WMAP) solar dipole. This allows our 2015 LFI analysis to provide an independent Solar dipole estimate, which is in excellent agreement with that of HFI and within 1σ (0.3% in amplitude) of the WMAP value. This 0.3% shift in the peak-to-peak dipole temperature from WMAP and a general overhaul of the iterative calibration code increases the overall level of the LFI maps by 0.45% (30 GHz), 0.64% (44 GHz), and 0.82% (70 GHz) in temperature with respect to the 2013 Planck data release, thus reducing the discrepancy with the power spectrum measured by WMAP. We estimate that the LFI calibration uncertainty is now at the level of 0.20% for the 70 GHz map, 0.26% for the 44 GHz map, and 0.35% for the 30 GHz map. We provide a detailed description of the impact of all the changes implemented in the calibration since the previous data release

    Planck 2015 results. VI. LFI mapmaking

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    This paper describes the mapmaking procedure applied to Planck Low Frequency Instrument (LFI) data. The mapmaking step takes as input the calibrated timelines and pointing information. The main products are sky maps of I, Q, and U Stokes components. For the first time, we present polarization maps at LFI frequencies. The mapmaking algorithm is based on a destriping technique, which is enhanced with a noise prior. The Galactic region is masked to reduce errors arising from bandpass mismatch and high signal gradients. We apply horn-uniform radiometer weights to reduce the effects of beam-shape mismatch. The algorithm is the same as used for the 2013 release, apart from small changes in parameter settings. We validate the procedure through simulations. Special emphasis is put on the control of systematics, which is particularly important for accurate polarization analysis. We also produce low-resolution versions of the maps and corresponding noise covariance matrices. These serve as input in later analysis steps and parameter estimation. The noise covariance matrices are validated through noise Monte Carlo simulations. The residual noise in the map products is characterized through analysis of half-ring maps, noise covariance matrices, and simulations

    Planck 2013 results. IX. HFI spectral response

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    The Planck High Frequency Instrument (HFI) spectral response was determined through a series of ground based tests conducted with the HFI focal plane in a cryogenic environment prior to launch. The main goal of the spectral transmission tests was to measure the relative spectral response (including out-of-band signal rejection) of all HFI detectors. This was determined by measuring the output of a continuously scanned Fourier transform spectrometer coupled with all HFI detectors. As there is no on-board spectrometer within HFI, the ground-based spectral response experiments provide the definitive data set for the relative spectral calibration of the HFI. The spectral response of the HFI is used in Planck data analysis and component separation, this includes extraction of CO emission observed within Planck bands, dust emission, Sunyaev-Zeldovich sources, and intensity to polarization leakage. The HFI spectral response data have also been used to provide unit conversion and colour correction analysis tools. Verifications of the HFI spectral response data are provided through comparisons with photometric HFI flight data. This validation includes use of HFI zodiacal emission observations to demonstrate out-of-band spectral signal rejection better than 10^8. The accuracy of the HFI relative spectral response data is verified through comparison with complementary flight-data based unit conversion coefficients and colour correction coefficients. These coefficients include those based upon HFI observations of CO, dust, and Sunyaev-Zeldovich emission. General agreement is observed between the ground-based spectral characterization of HFI and corresponding in-flight observations, within the quoted uncertainty of each; explanations are provided for any discrepancies.Comment: 27 pages, 28 figures, one of the papers associated with the 2013 Planck data releas
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