Abstract
Context
Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal.
Objective
To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC ...survival.
Design
MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999.
Patients
Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT.
Main Outcome Measure
Overall survival (OS) and progression-free survival determined by Kaplan-Meier method.
Results
Median OS and 1-year survival for the later cohort were 9 months 95% confidence interval (CI), 4 to 22 months and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort hazard ratio (HR), 0.32; P = 0.0006. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy.
Conclusion
MMT appears to convey longer survival in ATC among patients with stage IVA/B disease.
Intensive multimodal therapy appears to convey improved survival among patients with stage IVA/B ATC and should be considered among those accepting of substantial therapy-related toxicities.
We present an improved Global Sky Model (GSM) of diffuse Galactic radio emission from 10 MHz to 5 THz, whose uses include foreground modelling for cosmic microwave background (CMB) and 21 cm ...cosmology. Our model improves on past work both algorithmically and by adding new data sets such as the Planck maps and the enhanced Haslam map. Our method generalizes the principal component analysis approach to handle non-overlapping regions, enabling the inclusion of 29 sky maps with no region of the sky common to all. We also perform a blind separation of our GSM into physical components with a method that makes no assumptions about physical emission mechanisms (synchrotron, free-free, dust, etc). Remarkably, this blind method automatically finds five components that have previously only been found 'by hand', which we identify with synchrotron, free-free, cold dust, warm dust, and the CMB anisotropy. Computing the cross-power spectrum between these blindly extracted components and Planck component maps, we find a strong correlation at all angular scales. The improved GSM is available online at http://github.com/jeffzhen/gsm2016.
Astronomical wide-field imaging of interferometric radio data is computationally expensive, especially for the large data volumes created by modern non-coplanar many-element arrays. We present a new ...wide-field interferometric imager that uses the w-stacking algorithm and can make use of the w-snapshot algorithm. The performance dependences of casa's w-projection and our new imager are analysed and analytical functions are derived that describe the required computing cost for both imagers. On data from the Murchison Widefield Array, we find our new method to be an order of magnitude faster than w-projection, as well as being capable of full-sky imaging at full resolution and with correct polarization correction. We predict the computing costs for several other arrays and estimate that our imager is a factor of 2–12 faster, depending on the array configuration. We estimate the computing cost for imaging the low-frequency Square Kilometre Array observations to be 60 PetaFLOPS with current techniques. We find that combining w-stacking with the w-snapshot algorithm does not significantly improve computing requirements over pure w-stacking. The source code of our new imager is publicly released.
We present first results from radio observations with the Murchison Widefield Array seeking to constrain the power spectrum of 21 cm brightness temperature fluctuations between the redshifts of 11.6 ...and 17.9 (113 and 75 MHz). 3 h of observations were conducted over two nights with significantly different levels of ionospheric activity. We use these data to assess the impact of systematic errors at low frequency, including the ionosphere and radio-frequency interference, on a power spectrum measurement. We find that after the 1–3 h of integration presented here, our measurements at the Murchison Radio Observatory are not limited by RFI, even within the FM band, and that the ionosphere does not appear to affect the level of power in the modes that we expect to be sensitive to cosmology. Power spectrum detections, inconsistent with noise, due to fine spectral structure imprinted on the foregrounds by reflections in the signal-chain, occupy the spatial Fourier modes where we would otherwise be most sensitive to the cosmological signal. We are able to reduce this contamination using calibration solutions derived from autocorrelations so that we achieve an sensitivity of 104 mK on comoving scales k ≲ 0.5 h Mpc−1. This represents the first upper limits on the 21 cm power spectrum fluctuations at redshifts 12 ≲ z ≲ 18 but is still limited by calibration systematics. While calibration improvements may allow us to further remove this contamination, our results emphasize that future experiments should consider carefully the existence of and their ability to calibrate out any spectral structure within the EoR window.
To investigate the relationship between nutritional supplementation and radiation dose to the pharyngeal constrictor muscles and larynx for head and neck (HN) cancer patients undergoing radiotherapy.
...We retrospectively analyzed radiotherapy (RT) dose for 231 HN cancer patients, focusing on the pharyngeal constrictors and larynx. We defined nutritional supplementation as feeding tube utilization or >10% weight loss from baseline within 90 days after radiotherapy completion. Using deformable image registration (DIR), we mapped each patient's anatomical structures to a reference coordinate system, and corresponding deformations were applied to dose matrices. Voxel doses were utilized as features for ridge logistic regression models, optimized through 5-fold cross-validation. Model performance was assessed with area under the curve of a receiver operating curve (AUC) and F1 score. We built and compared models using 1) pharyngeal constrictor voxels, 2) larynx voxels, 3) clinical factors and mean regional dose metrics, and 4) clinical factors and dose-volume histogram metrics. Test set AUCs were compared among the models, and feature importance was evaluated.
DIR of the pharyngeal constrictors and larynx yielded mean Dice coefficients of 0.80 and 0.84, respectively. Pharyngeal constrictors voxels and larynx voxel models had AUC of 0.88 and 0.82, respectively. Voxel-based dose modeling identified the superior to middle regions of the pharyngeal constrictors and the superior region of larynx as most predictive of feeding tube use/weight loss. Univariate analysis found treatment setting, treatment laterality, chemotherapy, baseline dysphagia, weight, and socioeconomic status predictive of outcome. An aggregated model using mean doses of pharyngeal constrictors and larynx subregions had an AUC of 0.87 and the model using conventional DVH metrics had an AUC of 0.85 with p-value of 0.04. Feature importance calculations from the regional dose model indicated that mean doses to the superior-middle pharyngeal constrictor muscles followed by mean dose to the superior larynx were most predictive of nutritional supplementation.
Machine learning modeling of voxel-level doses enables identification of subregions within organs that correlate with toxicity. For HN radiotherapy, doses to the superior-middle pharyngeal constrictors are most predictive of feeding tube use/weight loss followed by the doses to superior portion of the larynx.
To determine whether N-acetylcysteine rinse was safe and could improve thickened secretions and dry mouth during and after radiotherapy.
We designed a prospective pilot double-blind, ...placebo-controlled randomized clinical trial (Alliance MC13C2). Adult patients (age ≥18 years) were enrolled if they underwent chemoradiotherapy (≥60 Gy). Patients initiated testing rinse within 3 days of starting radiotherapy. With swish-and-spit, they received 10% N-acetylcysteine (2500 mg daily) or placebo rinse solution 5 times daily during radiotherapy and 2 weeks postradiotherapy. The primary aim was to evaluate N-acetylcysteine in improvement of saliva viscosity with the Groningen Radiotherapy-Induced Xerostomia questionnaire. Secondary aims included evaluating xerostomia improvement by the same questionnaire and with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck-35 Questions survey and adverse-event profiles. The type I error rate was 20%.
Thirty-two patients undergoing chemoradiotherapy were enrolled. Baseline characteristics were balanced for placebo (n=17) and N-acetylcysteine (n=15). N-acetylcysteine was better for improving sticky saliva (area under curve, P=.12). Scores of multiple secondary end points favored N-acetylcysteine, including sticky saliva daytime (P=.04), daytime and total xerostomia (both P=.02), pain (P=.18), and trouble with social eating (P=.15). Repeated measures models confirmed the findings. Taste was a major dissatisifer for N-acetylcysteine rinse; however, both testing rinses were safe and well tolerated overall.
Our pilot data showed that N-acetylcysteine rinse was safe and provided strong evidence of potential efficacy for improving thickened saliva and xerostomia by patient-reported outcome. A confirmatory phase 3 trial is required.
clinicaltrials.gov Identifier: NCT02123511.
Interferometric arrays seeking to measure the 21 cm signal from the epoch of reionization (EOR) must contend with overwhelmingly bright emission from foreground sources. Accurate recovery of the 21 ...cm signal will require precise calibration of the array, and several new avenues for calibration have been pursued in recent years, including methods using redundancy in the antenna configuration. The newly upgraded Phase II of Murchison Widefield Array (MWA) is the first interferometer that has large numbers of redundant baselines while retaining good instantaneous UV coverage. This array therefore provides a unique opportunity to compare redundant calibration with sky-model-based algorithms. In this paper, we present the first results from comparing both calibration approaches with MWA Phase II observations. For redundant calibration, we use the package OMNICAL and produce sky-based calibration solutions with the analysis package Fast Holographic Deconvolution (FHD). There are three principal results: (1) We report the success of OMNICAL on observations of ORBComm satellites, showing substantial agreement between redundant visibility measurements after calibration. (2) We directly compare OMNICAL calibration solutions with those from FHD and demonstrate that these two different calibration schemes give extremely similar results. (3) We explore improved calibration by combining OMNICAL and FHD. We evaluate these combined methods using power spectrum techniques developed for EOR analysis and find evidence for marginal improvements mitigating artifacts in the power spectrum. These results are likely limited by the signal-to-noise ratio in the 6 hr of data used, but they suggest future directions for combining these two calibration schemes.
Experiments that pursue detection of signals from the Epoch of Reionization (EoR) are relying on spectral smoothness of source spectra at low frequencies. This article empirically explores the effect ...of foreground spectra on EoR experiments by measuring high-resolution full-polarization spectra for the 586 brightest unresolved sources in one of the Murchison Widefield Array (MWA) EoR fields using 45 h of observation. A novel peeling scheme is used to subtract 2500 sources from the visibilities with ionospheric and beam corrections, resulting in the deepest, confusion-limited MWA image so far. The resulting spectra are found to be affected by instrumental effects, which limit the constraints that can be set on source-intrinsic spectral structure. The sensitivity and power-spectrum of the spectra are analysed, and it is found that the spectra of residuals are dominated by point spread function sidelobes from nearby undeconvolved sources. We release a catalogue describing the spectral parameters for each measured source.
•Compared to VMAT, IMPT is associated with less PEG placement for the treatment of OPC.•IMPT is associated with decreased acute hospitalizations compared to VMAT.•Provider-reported acute toxicities ...show less mucositis, dysphagia, and pain with IMPT.•Patient-reported outcomes improved with IMPT included cough and dysgeusia.•Benefits were predominantly seen in those treated definitively or with adjuvant CRT.
IMPT improves normal tissue sparing compared to VMAT in treating oropharyngeal cancer (OPC). Our aim was to assess if this translates into clinical benefits.
OPC patients treated with definitive or adjuvant IMPT or VMAT from 2013 to 2018 were included. All underwent prospective assessment using patient-reported-outcomes (PROs) (EORTC-QLQ-H&N35) and provider-assessed toxicities (CTCAEv4.03). End-of-treatment and pretreatment scores were compared. PEG-tube use, hospitalization, and narcotic use were retrospectively collected. Statistical analysis used the Wilcoxon Rank-Sum Test with propensity matching for PROs/provider-assessed toxicities, and t-tests for other clinical outcomes.
46 IMPT and 259 VMAT patients were included; median follow-up was 12 months (IMPT) and 30 months (VMAT). Baseline characteristics were balanced except for age (p = 0.04, IMPT were older) and smoking (p < 0.01, 10.9% IMPT >20PYs, 29.3% VMAT). IMPT was associated with lower PEG placement (OR = 0.27; 95% CI: 0.12–0.59; p = 0.001) and less hospitalization ≤60 days post-RT (OR = 0.21; 95% CI:0.07–0.6, p < 0.001), with subgroup analysis revealing strongest benefits in patients treated definitively or with concomitant chemoradiotherapy (CRT). IMPT was associated with a relative risk reduction of 22.3% for end-of-treatment narcotic use. Patients reported reduced cough and dysgeusia with IMPT (p < 0.05); patients treated definitively or with CRT also reported feeling less ill, reduced feeding tube use, and better swallow. Provider-assessed toxicities demonstrated less pain and mucositis with IMPT, but more mucosal infection.
IMPT is associated with improved PROs, reduced PEG-tube placement, hospitalization, and narcotic requirements. Mucositis, dysphagia, and pain were decreased with IMPT. Benefits were predominantly seen in patients treated definitively or with CRT.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
Failure to recognize symptoms of non‐human papillomavirus‐associated oropharyngeal squamous cell carcinoma (HPV(−)OPSCC) at presentation can delay diagnosis and treatment. We aim to ...identify patient factors and provider practice patterns that delay presentation and care in HPV(−)OPSCC.
Methods
Retrospective review at a tertiary care center. Patients with HPV(−)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were ed. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care.
Results
Of 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32–127 days), with a median latency of 30 days (IQR = 12–61 days) from symptom onset to first presentation and 19.5 days (IQR = 4–46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis.
Conclusions
Delays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(−)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(−)OPSCC.
Level of Evidence
4 Laryngoscope, 133:1394–1401, 2023
Delays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(−)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(−)OPSCC.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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