A pilot study of same-day MRI-only simulation and treatment with MR-guided adaptive palliative radiotherapy (MAP-RT)

We conducted a prospective pilot study evaluating the feasibility of same day MRI-only simulation and treatment with MRI-guided adaptive palliative radiotherapy (MAP-RT) for urgent palliative indications (NCT#03824366). All (16/16) patients were able to complete 99% of their first on-table attempted fractions, and no grades 3-5 toxicities occurred

Association of Disease Recurrence With Survival Outcomes in Patients With Cutaneous Squamous Cell Carcinoma of the Head and Neck Treated With Multimodality Therapy

IMPORTANCE It has previously been demonstrated that immunosuppressed patients with cutaneous squamous cell cancer of the head and neck (cSCC-HN) treated with surgery and postoperative radiotherapy have significantly inferior disease-related outcomes compared with immunocompetent patients, but data on outcomes after disease recurrence are limited. OBJECTIVES To report survival outcomes in patients with cSCC-HN after disease recurrence after surgery and postoperative radiotherapy and to investigate the association of immune status with disease-related outcomes. DESIGN, SETTING, AND PARTICIPANTS A multi-institutional study of 205 patients treated at the Cleveland Clinic, Washington University in St Louis, and the University of California, San Francisco, in which patients who underwent surgical resection and postoperative radiotherapy for primary or recurrent stage I to IV (nonmetastatic) cSCC-HN between January 1, 1995, and December 31, 2014, were identified. Patients with any disease recurrence, defined as local, regional, and/or distant failure, were included. Patients were categorized as immunosuppressed if they received a diagnosis of chronic hematologic malignant neoplasm or HIV or AIDS, or were treated with immunosuppressive therapy for organ transplantation 6 months or more before diagnosis. Statistical analysis was conducted from January 1, 1995, to December 31, 2015. MAIN OUTCOMES AND MEASURES Overall survival calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS Of the 205 patients in the original cohort, 72 patients (63 men and 9 women; median age, 71 years [range, 43-91 years]) developed disease recurrence after surgery and postoperative radiotherapy. Forty patients (55.6%) were immunosuppressed, and 32 patients (44.4%) were immunocompetent. Locoregional recurrence was the most common first pattern of failure for both groups (31 immunosuppressed patients [77.5%]; 21 immunocompetent patients [65.6%]). After any recurrence, 1-year overall survival was 43.2%(95% CI, 30.9%-55.4%), and median survival was 8.4 months. For patients for whom information on salvage treatment was available (n = 45), those not amenable to surgical salvage had significantly poorer median cumulative incidence of survival compared with those who were amenable to surgical salvage (4.7 months; 95% CI, 3.7-7.0 months vs 26.1 months; 95% CI, 6.6 months to not reached; P=.01), regardless of their immune status. CONCLUSIONS AND RELEVANCE Results of this study suggest that patients with cSCC-HN who experience disease recurrence after definitive treatment with surgery and postoperative radiotherapy have poor survival, irrespective of immune status. Survival rates are low for patients with recurrent disease that is not amenable to surgical salvage. The low rate of successful salvage underscores the importance of intensifying upfront treatment to prevent recurrence.12 month embargo; published online: 27 February 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma

In serum, the major part of vascular endothelial growth factor derives from in vitro degranulation of granulocytes and platelets. Therefore, plasma may be preferred for vascular endothelial growth factor measurements. However, which specimen is the best predictor of survival is still debated. The present study analyzed the prognostic value of matched preoperative serum and plasma vascular endothelial growth factor concentrations in patients with colorectal cancer. To establish the reference range among healthy people, vascular endothelial growth factor was analyzed in 50 matched EDTA-plasma and serum samples from healthy blood donors. Preoperatively, in 524 patients with colorectal cancer, matched plasma and serum vascular endothelial growth factor concentrations were analyzed. In the colorectal cancer patients, the median plasma vascular endothelial growth factor concentration (44 pg ml−1) was significantly (P=0.01) higher than the median plasma vascular endothelial growth factor concentration (30 pg ml−1) in the healthy blood donors. In serum, no significant (P=0.30) difference in the median vascular endothelial growth factor concentration was found between colorectal cancer patients (268 pg ml−1) and healthy blood donors (220 pg ml−1). The preoperative vascular endothelial growth factor concentrations were dichotomized by the 95th percentile of the healthy blood donors (plasma=112 pg ml−1, serum=533 pg ml−1). In univariate survival analyses, both high plasma vascular endothelial growth factor (>112 pg ml−1) and high serum vascular endothelial growth factor (>533 pg ml−1) predicted a reduced survival. In multivariate survival analyses, high serum vascular endothelial growth factor (>533 pg ml−1) independently predicted a reduced survival (HR=1.65, P=0.015), while high plasma vascular endothelial growth factor (>112 pg ml−1) did not (HR=1.27, P=0.23). This study indicates that preoperative serum vascular endothelial growth factor apparently is a better predictor of overall survival than the preoperative plasma vascular endothelial growth factor

Clinical outcomes of patients with unresectable primary liver cancer treated with yttrium-90 radioembolization with an escalated dose

PURPOSE: Yttrium-90 (90Y) radioembolization with an escalated dose has been shown to improve clinical outcomes compared with standard dose radioembolization, but there are few data on the local control of primary liver tumors. We reported the clinical outcomes of patients with unresectable primary liver tumors treated with 90Y radioembolization with an escalated dose. METHODS AND MATERIALS: Clinical data of patients with unresectable hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and biphenotypic tumors (cHCC-CC) treated with radioembolization with an escalated dose (≥150 Gy) between 2013 and 2020 with \u3e3 months follow-up were retrospectively reviewed. The primary endpoint was freedom from local progression. Clinical response was defined by Modified Response Evaluation Criteria in Solid Tumours and toxic effects were assessed using Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Fifty-three patients with HCC and 15 patients with CC/cHCC-CC were analyzed. The median dose delivered was 205 Gy (interquartile range, 183-253 Gy) and 198 Gy (interquartile range, 154-234 Gy) for patients with HCC and CC/cHCC-CC, respectively. The 1-year freedom from local progression rate was 54% (95% confidence interval [CI], 38%-78%) for patients with HCC and 66% (95% CI, 42%-100%) for patients with CC/cHCC-CC. For patients with HCC, United Network for Organ Sharing nodal stage 1 ( CONCLUSIONS: Treatment of unresectable primary liver tumors with 90Y radioembolization with an escalated dose was safe and well tolerated. Delivery of \u3e268 Gy may improve local tumor control of HCC. Determination of the maximum tolerated dose needs to be performed in the context of future prospective dose-escalation trials to further evaluate the safety and efficacy of such an approach

Cost-effectiveness of total neoadjuvant therapy with short-course radiotherapy for resectable locally advanced rectal cancer

Importance: Short-course radiotherapy and total neoadjuvant therapy (SCRT-TNT) followed by total mesorectal excision (TME) has emerged as a new treatment paradigm for patients with locally advanced rectal adenocarcinoma. However, the economic implication of this treatment strategy has not been compared with that of conventional long-course chemoradiotherapy (LCCRT) followed by TME with adjuvant chemotherapy. Objective: To perform a cost-effectiveness analysis of SCRT-TNT vs LCCRT in conjunction with TME for patients with locally advanced rectal cancer. Design, Setting, and Participants: A decision analytical model with a 5-year time horizon was constructed for patients with biopsy-proven, newly diagnosed, primary locally advanced rectal adenocarcinoma treated with SCRT-TNT or LCCRT. Markov modeling was used to model disease progression and patient survival after treatment in 3-month cycles. Data on probabilities and utilities were extracted from the literature. Costs were evaluated from the Medicare payer\u27s perspective in 2020 US dollars. Sensitivity analyses were performed for key variables. Data were collected from October 3, 2020, to January 20, 2021, and analyzed from November 15, 2020, to April 25, 2021. Exposures: Two treatment strategies, SCRT-TNT vs LCCRT with adjuvant chemotherapy, were compared. Main Outcomes and Measures: Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio and net monetary benefits. Effectiveness was defined as quality-adjusted life-years (QALYs). Both costs and QALYs were discounted at 3% annually. Willingness-to-pay threshold was set at $50 000/QALY. Results: During the 5-year horizon, the total cost was$41 355 and QALYs were 2.21 for SCRT-TNT; for LCCRT, the total cost was $54 827 and QALYs were 2.12, resulting in a negative incremental cost-effectiveness ratio (-$141 256.77). The net monetary benefit was $69 300 for SCRT-TNT and$51 060 for LCCRT. Sensitivity analyses using willingness to pay at $100 000/QALY and$150 000/QALY demonstrated the same conclusion. Conclusions and Relevance: These findings suggest that SCRT-TNT followed by TME incurs lower cost and improved QALYs compared with conventional LCCRT followed by TME and adjuvant chemotherapy. These data offer further rationale to support SCRT-TNT as a novel cost-saving treatment paradigm in the management of locally advanced rectal cancer

Learning pair-wise gene functional similarity by multiplex gene expression maps

Abstract Background The relationships between the gene functional similarity and gene expression profile, and between gene function annotation and gene sequence have been studied extensively. However, not much work has considered the connection between gene functions and location of a gene's expression in the mammalian tissues. On the other hand, although unsupervised learning methods have been commonly used in functional genomics, supervised learning cannot be directly applied to a set of normal genes without having a target (class) attribute. Results Here, we propose a supervised learning methodology to predict pair-wise gene functional similarity from multiplex gene expression maps that provide information about the location of gene expression. The features are extracted from expression maps and the labels denote the functional similarities of pairs of genes. We make use of wavelet features, original expression values, difference and average values of neighboring voxels and other features to perform boosting analysis. The experimental results show that with increasing similarities of gene expression maps, the functional similarities are increased too. The model predicts the functional similarities between genes to a certain degree. The weights of the features in the model indicate the features that are more significant for this prediction. Conclusions By considering pairs of genes, we propose a supervised learning methodology to predict pair-wise gene functional similarity from multiplex gene expression maps. We also explore the relationship between similarities of gene maps and gene functions. By using AdaBoost coupled with our proposed weak classifier we analyze a large-scale gene expression dataset and predict gene functional similarities. We also detect the most significant single voxels and pairs of neighboring voxels and visualize them in the expression map image of a mouse brain. This work is very important for predicting functions of unknown genes. It also has broader applicability since the methodology can be applied to analyze any large-scale dataset without a target attribute and is not restricted to gene expressions

Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet

Optical Magnetometry

Some of the most sensitive methods of measuring magnetic fields utilize interactions of resonant light with atomic vapor. Recent developments in this vibrant field are improving magnetometers in many traditional areas such as measurement of geomagnetic anomalies and magnetic fields in space, and are opening the door to new ones, including, dynamical measurements of bio-magnetic fields, detection of nuclear magnetic resonance (NMR), magnetic-resonance imaging (MRI), inertial-rotation sensing, magnetic microscopy with cold atoms, and tests of fundamental symmetries of Nature.Comment: 11 pages; 4 figures; submitted to Nature Physic

All-sky search for periodic gravitational waves in LIGO S4 data

We report on an all-sky search with the LIGO detectors for periodic gravitational waves in the frequency range 50-1000 Hz and with the frequency's time derivative in the range -1.0E-8 Hz/s to zero. Data from the fourth LIGO science run (S4) have been used in this search. Three different semi-coherent methods of transforming and summing strain power from Short Fourier Transforms (SFTs) of the calibrated data have been used. The first, known as "StackSlide", averages normalized power from each SFT. A "weighted Hough" scheme is also developed and used, and which also allows for a multi-interferometer search. The third method, known as "PowerFlux", is a variant of the StackSlide method in which the power is weighted before summing. In both the weighted Hough and PowerFlux methods, the weights are chosen according to the noise and detector antenna-pattern to maximize the signal-to-noise ratio. The respective advantages and disadvantages of these methods are discussed. Observing no evidence of periodic gravitational radiation, we report upper limits; we interpret these as limits on this radiation from isolated rotating neutron stars. The best population-based upper limit with 95% confidence on the gravitational-wave strain amplitude, found for simulated sources distributed isotropically across the sky and with isotropically distributed spin-axes, is 4.28E-24 (near 140 Hz). Strict upper limits are also obtained for small patches on the sky for best-case and worst-case inclinations of the spin axes.Comment: 39 pages, 41 figures An error was found in the computation of the C parameter defined in equation 44 which led to its overestimate by 2^(1/4). The correct values for the multi-interferometer, H1 and L1 analyses are 9.2, 9.7, and 9.3, respectively. Figure 32 has been updated accordingly. None of the upper limits presented in the paper were affecte