Empiric Radiotherapy for Lung Cancer Collaborative Group multi-institutional evidence-based guidelines for the use of empiric stereotactic body radiation therapy for non-small cell lung cancer without pathologic confirmation

The standard of care for managing early stage non-small cell lung cancer (NSCLC) is definitive surgical resection. Stereotactic body radiation therapy (SBRT) has become the standard treatment for patient who are medically inoperable, and it is increasingly being considered as an option in operable patients. With the growing use of screening thoracic CT scans for patients with a history of heavy smoking, as well as improved imaging capabilities, the discovery of small lung nodes has become a common dilemma. As a result, clinicians are increasingly faced with managing lung nodules in patients in whom diagnostic biopsy is not safe or feasible. Herein, we describe the scope of the problem, tools available for predicting the probability that a lung nodule is a malignancy, staging procedures, benefits of pathology-proven and empiric SBRT, considerations of safety based on location of the lesion of concern, and overall efficacy of SBRT

American Radium Society (ARS) and American College of Radiology (ACR) Appropriate Use Criteria Systematic Review and Guidelines on Reirradiation for Non-small Cell Lung Cancer (NSCLC)

Background: Reirradiation (reRT) for locoregional recurrences can provide durable control and improved symptoms and progression-free survival for select NSCLC patients. Thoracic reRT, however, is particularly challenging due to its considerable risk and the current lack of standardized approaches, guidelines and dose constraints. To date, no systematic review on the safety and efficacy of reRT for NSCLC exists, and no dedicated guidelines are available. Objectives: This ARS-ACR Appropriate Use Criteria Systematic Review and Guidelines on Reirradiation for NSCLC provides direct guidance on the safety and efficacy of reRT and recommends consensus dose constraints for thoracic reRT to minimize risks of high grade toxicities. Methods: A PRISMA systematic review assessed all studies published through 3/2019 evaluating toxicities, local control and/or overall survival for NSCLC thoracic reRT. Of 236 articles, 49 remained after exclusions (3 prospective) and formed the basis for these recommendations on: 1) the role of concurrent chemotherapy with reRT, 2) factors associated with toxicity from reRT and 3) what reRT modalities, dose-fractionation schemas and dose rates should be used. Composite dose constraints were also recommended. The available data suggest potential benefit in clinical outcomes with concurrent chemoradiation for reRT, but the decision should be based on patient performance status, tolerance to prior systemic therapy and other individual patient/tumor characteristics. There are no data to guide the use of concurrent targeted therapy or immunotherapy with reRT, and this is not recommended outside of a clinical trial. Acute esophagitis and pneumonitis and late pulmonary, cardiac/great vessel, esophageal, brachial plexus and spinal toxicities are dose limiting for reRT. Limited data exist regarding the use of hyperfractionation and low- or high-dose rate reRT for NSCLC. For conventionally fractionated reRT, intensity-modulated radiation therapy (IMRT) is recommended over 3D conformal radiation therapy (3DCRT) to increase dose conformality. Particle therapy may further reduce toxicities and/or enable safer reRT dose escalation compared with 3DCRT and IMRT. Stereotactic body radiation therapy (SBRT) can provide increased conformality and dose escalation and is optimal for primary-alone failures, but caution is needed for central reRT with SBRT. Recommended reRT composite dose constraints in 2 Gy equivalent dose are: esophagus V60 \u3c40% and DMax \u3c100-110 Gy, lung V20 \u3c40%, heart V40 \u3c50%, aorta/great vessels DMax \u3c120 Gy, trachea and proximal bronchial tree DMax \u3c110 Gy, spinal cord DMax \u3c57 Gy, and brachial plexus DMax \u3c85 Gy. Conclusions: For the first time, consensus dose constraints for thoracic reRT are recommended to minimize the risks of high-grade and potentially fatal toxicities from repeat radiotherapy. Additional prospective data are needed, and toxicities should be correlated with reRT course and composite dose constraints

La deficiencia de zinc prepara al pulmón para las lesiones inducidas por el ventilador

Mechanical ventilation is necessary to support patients with acute lung injury, but also exacerbates injury through mechanical stress–activated signaling pathways. We show that stretch applied to cultured human cells, and to mouse lungs in vivo, induces robust expression of metallothionein, a potent antioxidant and cytoprotective molecule critical for cellular zinc homeostasis. Furthermore, genetic deficiency of murine metallothionein genes exacerbated lung injury caused by high tidal volume mechanical ventilation, identifying an adaptive role for these genes in limiting lung injury. Stretch induction of metallothionein required zinc and the zinc-binding transcription factor MTF1. We further show that mouse dietary zinc deficiency potentiates ventilator-induced lung injury, and that plasma zinc levels are significantly reduced in human patients who go on to develop acute respiratory distress syndrome (ARDS) compared with healthy and non-ARDS intensive care unit (ICU) controls, as well as with other ICU patients without ARDS. Taken together, our findings identify a potentially novel adaptive response of the lung to stretch and a critical role for zinc in defining the lung’s tolerance for mechanical ventilation. These results demonstrate that failure of stretch-adaptive responses play an important role in exacerbating mechanical ventilator–induced lung injury, and identify zinc and metallothionein as targets for lung-protective interventions in patients requiring mechanical ventilation

Proton Therapy for Breast Cancer:A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. (c) 2021 Elsevier Inc. All rights reserved

Prospective evaluation of patient-reported outcomes of invisible ink tattoos for the delivery of external beam radiation therapy: the PREFER trial

IntroductionInvisible ink tattoos (IITs) avoid cosmetic permanence of visible ink tattoos (VITs) while serving as more reliable landmarks for radiation setup than tattooless setups. This trial evaluated patient-reported preference and feasibility of IIT implementation.Methods and materialsIn an IRB-approved, single institution, prospective trial, patients receiving proton therapy underwent IIT-based treatment setup. A survey tool assessed patient preference on tattoos using a Likert scale. Matched patients treated using our institutional standard tattooless setup were identified; treatment times and image guidance requirements were evaluated between tattooless and IIT-based alignment approaches. Distribution differences were estimated using Wilcoxon rank-sum tests or Chi-square tests.ResultsOf 94 eligible patients enrolled, median age was 58 years, and 58.5% were female. Most common treatment sites were breast (18.1%), lung (17.0%) and pelvic (14.9%). Patients preferred to receive IITs versus VITs (79.8% pre-treatment and 75.5% post-treatment, respectively). Patients were willing to travel farther from home to avoid VITs versus IITs (p<0.01). Females were willing to travel (45.5% vs. 23.1%; p=0.04) and pay additional money to avoid VITs (34.5% vs. 5.1%; p<0.01). Per-fraction average +treatment time and time from on table/in room to first beam were shorter with IIT-based vs. tattooless setup (12.3min vs. 14.1min; p=0.04 and 24.1min vs. 26.2min; p=0.02, respectively).DiscussionIn the largest prospective trial on IIT-based radiotherapy setup to date, we found that patients prefer IITs to VITs. Additionally, IIT-based alignment is an effective and efficient strategy in comparison with tattooless setup. Standard incorporation of IITs for patient setup should be strongly considered

ALMA ACA and Nobeyama Observations of Two Orion Cores in Deuterated Molecular Lines

We mapped two molecular cloud cores in the Orion A cloud with the 7 m Array of the Atacama Compact Array (ACA) of the Atacama Large Millimeter/submillimeterArray (ALMA) and with the Nobeyama 45 m radio telescope. These cores have bright N2D+ emission in single-pointing observations with the Nobeyama 45 m radio telescope, have a relatively high deuterium fraction, and are thought to be close to the onset of star formation. One is a star-forming core, and the other is starless. These cores are located along filaments observed in N2H+ and show narrow line widths of 0.41 km s(-1) and 0.45 km s(-1) in N2D+, respectively, with the Nobeyama 45 m telescope. Both cores were detected with the ALMA ACA 7 m Array in the continuum and molecular lines at Band 6. The starless core G211 shows a clumpy structure with several sub-cores, which in turn show chemical differences. Also, the sub-cores in G211 have internal motions that are almost purely thermal. The starless sub-core G211D, in particular, shows a hint of the inverse P Cygni profile, suggesting infall motion. The star-forming core G210 shows an interesting spatial feature of two N2D+ peaks of similar intensity and radial velocity located symmetrically with respect to the single dust continuum peak. One interpretation is that the two N2D+ peaks represent an edge-on pseudo-disk. The CO outflow lobes, however, are not directed perpendicular to the line connecting both N2D+ peaks.Peer reviewe

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Sodium/myo-Inositol Transporters: Substrate Transport Requirements and Regional Brain Expression in the TgCRND8 Mouse Model of Amyloid Pathology

Inositol stereoisomers, myo- and scyllo-inositol, are known to enter the brain and are significantly elevated following oral administration. Elevations in brain inositol levels occur across a concentration gradient as a result of active transport from the periphery. There are two sodium/myo-inositol transporters (SMIT1, SMIT2) that may be responsible for regulating brain inositol levels. The goals of this study were to determine the effects of aging and Alzheimer's disease (AD)-like amyloid pathology on transporter expression, to compare regional expression and to analyze substrate requirements of the inositol transporters. QPCR was used to examine expression of the two transporters in the cortex, hippocampus and cerebellum of TgCRND8 mice, a mouse model of amyloid pathology, in comparison to non-transgenic littermates. In addition, we examined the structural features of inositol required for active transport, utilizing a cell-based competitive uptake assay. Disease pathology did not alter transporter expression in the cortex or hippocampus (p>0.005), with only minimal effects of aging observed in the cerebellum (SMIT1: F2,26 = 12.62; p = 0.0002; SMIT2: F2,26 = 8.71; p = 0.0015). Overall, brain SMIT1 levels were higher than SMIT2, however, regional differences were observed. For SMIT1, at 4 and 6 months cerebellar SMIT1 levels were significantly higher than cortical and hippocampal levels (p<0.05). For SMIT2, at all three ages both cortical and cerebellar SMIT2 levels were significantly higher than hippocampal levels (p<0.05) and at 4 and 6 months of age, cerebellar SMIT2 levels were also significantly higher than cortical levels (p<0.05). Inositol transporter levels are stably expressed as a function of age, and expression is unaltered with disease pathology in the TgCRND8 mouse. Given the fact that scyllo-inositol is currently in clinical trials for the treatment of AD, the stable expression of inositol transporters regardless of disease pathology is an important finding

Molecular Cloud Cores with a High Deuterium Fraction : Nobeyama Single-pointing Survey

We present the results of a single-pointing survey of 207 dense cores embedded in Planck Galactic Cold Clumps distributed in five different environments (lambda Orionis, Orion A, Orion B, the Galactic plane, and high latitudes) to identify dense cores on the verge of star formation for the study of the initial conditions of star formation. We observed these cores in eight molecular lines at 76-94 GHz using the Nobeyama 45 m telescope. We find that early-type molecules (e.g., CCS) have low detection rates and that late-type molecules (e.g., N(2)H(+)and c-C3H2) and deuterated molecules (e.g., N(2)D(+)and DNC) have high detection rates, suggesting that most of the cores are chemically evolved. The deuterium fraction (D/H) is found to decrease with increasing distance, indicating that it suffers from differential beam dilution between the D/H pair of lines for distant cores (>1 kpc). For lambda Orionis, Orion A, and Orion B located at similar distances, D/H is not significantly different, suggesting that there is no systematic difference in the observed chemical properties among these three regions. We identify at least eight high-D/H cores in the Orion region and two at high latitudes, which are most likely to be close to the onset of star formation. There is no clear evidence of the evolutionary change in turbulence during the starless phase, suggesting that the dissipation of turbulence is not a major mechanism for the beginning of star formation as judged from observations with a beam size of 0.04 pc.Peer reviewe