First CLAS12 Measurement of Deeply Virtual Compton Scattering Beam-Spin Asymmetries in the Extended Valence Region.

Deeply virtual Compton scattering (DVCS) allows one to probe generalized parton distributions describing the 3D structure of the nucleon. We report the first measurement of the DVCS beam-spin asymmetry using the CLAS12 spectrometer with a 10.2 and 10.6 GeV electron beam scattering from unpolarized protons. The results greatly extend the Q^{2} and Bjorken-x phase space beyond the existing data in the valence region and provide 1600 new data points measured with unprecedented statistical uncertainty, setting new, tight constraints for future phenomenological studies.

Observation of Correlations between Spin and Transverse Momenta in Back-to-Back Dihadron Production at CLAS12.

We report the first measurements of deep inelastic scattering spin-dependent azimuthal asymmetries in back-to-back dihadron electroproduction in the deep inelastic scattering process. In this reaction, two hadrons are produced in opposite hemispheres along the z axis in the virtual photon-target nucleon center-of-mass frame, with the first hadron produced in the current-fragmentation region and the second in the target-fragmentation region. The data were taken with longitudinally polarized electron beams of 10.2 and 10.6 GeV incident on an unpolarized liquid-hydrogen target using the CLAS12 spectrometer at Jefferson Lab. Observed nonzero sinΔϕ modulations in ep→e^{'}pπ^{+}X events, where Δϕ is the difference of the azimuthal angles of the proton and pion in the virtual photon and target nucleon center-of-mass frame, indicate that correlations between the spin and transverse momenta of hadrons produced in the target- and current-fragmentation regions may be significant. The measured beam-spin asymmetries provide a first access in dihadron production to a previously unexplored leading-twist spin- and transverse-momentum-dependent fracture function. The fracture functions describe the hadronization of the target remnant after the hard scattering of a virtual photon off a quark in the target particle and provide a new avenue for studying nucleonic structure and hadronization.

Observation of Azimuth-Dependent Suppression of Hadron Pairs in Electron Scattering off Nuclei.

We present the first measurement of dihadron angular correlations in electron-nucleus scattering. The data were taken with the CLAS detector and a 5.0 GeV electron beam incident on deuterium, carbon, iron, and lead targets. Relative to deuterium, the nuclear yields of charged-pion pairs show a strong suppression for azimuthally opposite pairs, no suppression for azimuthally nearby pairs, and an enhancement of pairs with large invariant mass. These effects grow with increased nuclear size. The data are qualitatively described by the gibuu model, which suggests that hadrons form near the nuclear surface and undergo multiple scattering in nuclei.These results show that angular correlation studies can open a new way to elucidate how hadrons form and interact inside nuclei.

Multidimensional, High Precision Measurements of Beam Single Spin Asymmetries in Semi-inclusive π

High precision measurements of the polarized electron beam-spin asymmetry in semi-inclusive deep inelastic scattering (SIDIS) from the proton have been performed using a 10.6 GeV incident electron beam and the CLAS12 spectrometer at Jefferson Lab. We report here a high precision multidimensional study of single π^{+} SIDIS data over a large kinematic range in Bjorken x, fractional energy, and transverse momentum of the hadron as well as photon virtualities Q^{2} ranging from 1-7 GeV^{2}. In particular, the structure function ratio F_{LU}^{sinϕ}/F_{UU} has been determined, where F_{LU}^{sinϕ} is a twist-3 quantity that can reveal novel aspects of emergent hadron mass and quark-gluon correlations within the nucleon. The data's impact on the evolving understanding of the underlying reaction mechanisms and their kinematic variation is explored using theoretical models for the different contributing transverse momentum dependent parton distribution functions.

Observation of Beam Spin Asymmetries in the Process ep→e

The observation of beam spin asymmetries in two-pion production in semi-inclusive deep inelastic scattering off an unpolarized proton target is reported. The data presented here were taken in the fall of 2018 with the CLAS12 spectrometer using a 10.6 GeV longitudinally spin-polarized electron beam delivered by CEBAF at JLab. The measured asymmetries provide the first opportunity to extract the parton distribution function e(x), which provides information about the interaction between gluons and quarks, in a collinear framework that offers cleaner access than previous measurements. The asymmetries also constitute the first ever signal sensitive to the helicity-dependent two-pion fragmentation function G_{1}^{⊥}. A clear sign change is observed around the ρ mass that appears in model calculations and is indicative of the dependence of the produced pions on the helicity of the fragmenting quark.

Beam Spin Asymmetry in Semi-Inclusive Electroproduction of Hadron Pairs.

A first measurement of the longitudinal beam spin asymmetry A_{LU} in the semi-inclusive electroproduction of pairs of charged pions is reported. A_{LU} is a higher-twist observable and offers the cleanest access to the nucleon twist-3 parton distribution function e(x). Data have been collected in the Hall-B at Jefferson Lab by impinging a 5.498-GeV electron beam on a liquid-hydrogen target, and reconstructing the scattered electron and the pion pair with the CLAS detector. One-dimensional projections of the A_{LU}^{sinϕ_{R}} moments are extracted for the kinematic variables of interest in the valence quark region. The understanding of dihadron production is essential for the interpretation of observables in single-hadron production in semi-inclusive DIS, and pioneering measurements of single-spin asymmetries in dihadron production open a new avenue in studies of QCD dynamics.

Extraction of Beam-Spin Asymmetries from the Hard Exclusive π

We have measured beam-spin asymmetries to extract the sinϕ moment A_{LU}^{sinϕ} from the hard exclusive e[over →]p→e^{'}nπ^{+} reaction above the resonance region, for the first time with nearly full coverage from forward to backward angles in the center of mass. The A_{LU}^{sinϕ} moment has been measured up to 6.6 GeV^{2} in -t, covering the kinematic regimes of generalized parton distributions (GPD) and baryon-to-meson transition distribution amplitudes (TDA) at the same time. The experimental results in very forward kinematics demonstrate the sensitivity to chiral-odd and chiral-even GPDs. In very backward kinematics where the TDA framework is applicable, we found A_{LU}^{sinϕ} to be negative, while a sign change was observed near 90° in the center of mass. The unique results presented in this Letter will provide critical constraints to establish reaction mechanisms that can help to further develop the GPD and TDA frameworks.

Chest wall toxicity after stereotactic radiation in early lung cancer: a systematic review.

Background: Radiation-induced chest wall pain (cwp) and rib fracture (rf) are late adverse effects after stereotactic body radiation therapy (sbrt) for stage i non-small-cell lung cancer (nsclc); however, the literature about their incidence and risk factors shows variability. We performed a systematic review to determine the pooled incidence of cwp and rf in the relevant population. Methods: A literature search using the prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines considered English publications in medline and embase from January 1996 to August 2017. Abstracts were screened, followed by full-text review and data extraction. Results: The database searches identified 547 records. Twenty-eight publications comprising 3892 patients met the inclusion criteria. Median reported ages and follow-up durations fell into the ranges 67-82 years and 12-84 months. Prescriptions fell into the range of 40-70 Gy in 3-10 fractions. Despite study heterogeneity, the pooled incidences of cwp and rf were estimated to be 8.94% and 5.27% respectively. Nineteen studies reported cwp grade: 58 of 308 patients (18.8%) experienced grades 3-4 cwp (no grade 5 events reported). Thirteen studies reported rf grade: grades 3-4 rf were observed in 9 of 113 patients (7.96%). A high chest wall V30 was an important predictor of cwp and rf. Conclusions: In patients with stage i nsclc, rates of cwp and rf after sbrt are low; however, tumour location, accurate toxicity reporting, and dose-fractionation schemes might alter those rates. Prospective correlation with dosimetry and quality of life assessment will further improve the understanding of cwp and rf after sbrt.

Organizational guidance for the care of patients with head-and-neck cancer in Ontario.

Background: At the request of the Head and Neck Cancers Advisory Committee of Ontario Health (Cancer Care Ontario), a working group and expert panel of clinicians with expertise in the management of head-and-neck cancer developed the present guideline. The purpose of the guideline is to provide advice about the organization and delivery of health care services for adult patients with head-and-neck cancer. Methods: This document updates the recommendations published in the Ontario Health (Cancer Care Ontario) 2009 organizational guideline The Management of Head and Neck Cancer in Ontario. The guideline development methods included an updated literature search, internal review by content and methodology experts, and external review by relevant health care providers and potential users. Results: To ensure that all patients have access to the highest standard of care available in Ontario, the guideline establishes the minimum requirements to maintain a head-and-neck disease site program. Recommendations are made about the membership of core and extended provider teams, minimum skill sets and experience of practitioners, cancer centre-specific and practitioner-specific volumes, multidisciplinary care requirements, and unique infrastructure demands. Conclusions: The recommendations contained in this document offer guidance for clinicians and institutions providing care for patients with head-and-neck cancer in Ontario, and for policymakers and other stakeholders involved in the delivery of health care services for head-and-neck cancer.

Bone Health and Bone-targeted Therapies for Prostate Cancer: a Programme in Evidence-based Care - Cancer Care Ontario Clinical Practice Guideline.

AIMS: To make recommendations with respect to bone health and bone-targeted therapies in men with prostate cancer. MATERIALS AND METHODS: A systematic review was carried out by searching MEDLINE, EMBASE and the Cochrane Library from inception to January 2016. Systematic reviews and randomised-controlled trials were considered for inclusion if they involved therapies directed at improving bone health or outcomes such as skeletal-related events, pain and quality of life in patients with prostate cancer either with or without metastases to bone. Therapies included medications, supplements or lifestyle modifications alone or in combination and were compared with placebo, no treatment or other agents. Disease-targeted agents such as androgen receptor-targeted and chemotherapeutic agents were excluded. Recommendations were reviewed by internal and external review groups. RESULTS: In men with prostate cancer receiving androgen deprivation therapy, baseline bone mineral density testing is encouraged. Denosumab should be considered for reducing the risk of fracture in men on androgen deprivation therapy with an increased fracture risk. Bisphosphonates were effective in improving bone mineral density, but the effect on fracture was inconclusive. No medication is recommended to prevent the development of first bone metastasis. Denosumab and zoledronic acid are recommended for preventing or delaying skeletal-related events in men with metastatic castration-resistant prostate cancer. Radium-223 is recommended for reducing symptomatic skeletal events and prolonging survival in men with symptomatic metastatic castration-resistant prostate cancer. CONCLUSIONS: The recommendations represent a current standard of care that is feasible to implement, with outcomes valued by clinicians and patients.

Approach to evaluation of fever in ambulatory cancer patients receiving chemotherapy: A systematic review.

PURPOSE: To define the optimal model of care for patients receiving outpatient chemotherapy who experience a fever. Fever is a common symptom in patients receiving chemotherapy, but the approach to evaluation of fever is not standardized. METHODS: We conducted a search for existing guidelines and a systematic review of the primary literature from database inception to November 2015. Full-text reports and conference abstracts were considered for inclusion. The search focused on the following topics: the relationship between temperature and poor outcome; predictors for the development of febrile neutropenia (FN); the timing, location, and personnel involved in fever assessment; and the provision of information to patients receiving chemotherapy. RESULTS: Eight guidelines and 38 studies were included. None of the guidelines were directly relevant to the target population because they dealt primarily with the management of FN after diagnosis. The primary studies tended to include fever as one of many symptoms assessed in the setting of chemotherapy. Temperature level was a weak predictor of poor outcomes. We did not find validated prediction models for identifying patients at risk of FN among patients receiving chemotherapy. Several studies presented approaches to symptom management that included fever among the symptoms, but results were not mature enough to merit widespread adoption. CONCLUSION: Despite the frequency and risks of fever in the setting of chemotherapy, there is limited evidence to define who needs urgent assessment, where the assessment should be performed, and how quickly. Future research in this area is greatly needed to inform new models of care.

Approach to fever assessment in ambulatory cancer patients receiving chemotherapy: a clinical practice guideline.

BACKGROUND: This guideline was prepared by the Fever Assessment Guideline Development Group, a group organized by the Program in Evidence-Based Care at the request of the Cancer Care Ontario Systemic Treatment Program. The mandate was to develop a standardized approach (in terms of definitions, information, and education) for the assessment of fever in cancer patients receiving chemotherapy. METHODS: The guideline development methods included a search for existing guidelines, literature searches in medline and embase for systematic reviews and primary studies, internal review by content and methodology experts, and external review by targeted experts and intended users. RESULTS: The search identified eight guidelines that had partial relevance to the topic of the present guideline and thirty-eight primary studies. The studies were mostly noncomparative prospective or retrospective studies. Few studies directly addressed the topic of fever except as one among many symptoms or adverse effects associated with chemotherapy. The recommendations concerning fever definition are supported mainly by other existing guidelines. No evidence was found that directly pertained to the assessment of fever before a diagnosis of febrile neutropenia was made. However, some studies evaluated approaches to symptom management that included fever among the symptoms. Few studies directly addressed information needs and resources for managing fever in cancer patients. CONCLUSIONS: Fever in patients with cancer who are receiving systemic therapy is a common and potentially serious symptom that requires prompt assessment, but currently, evidence to inform best practices concerning when, where, and by whom that assessment is done is very limited.

Centrality and Transverse Momentum Dependence of Elliptic Flow of Multistrange Hadrons and ϕ Meson in Au+Au Collisions at √[sNN]=200 GeV.

We present high precision measurements of elliptic flow near midrapidity (|y|<1.0) for multistrange hadrons and ϕ meson as a function of centrality and transverse momentum in Au+Au collisions at center of mass energy √[sNN]=200 GeV. We observe that the transverse momentum dependence of ϕ and Ω v2 is similar to that of π and p, respectively, which may indicate that the heavier strange quark flows as strongly as the lighter up and down quarks. This observation constitutes a clear piece of evidence for the development of partonic collectivity in heavy-ion collisions at the top RHIC energy. Number of constituent quark scaling is found to hold within statistical uncertainty for both 0%-30% and 30%-80% collision centrality. There is an indication of the breakdown of previously observed mass ordering between ϕ and proton v2 at low transverse momentum in the 0%-30% centrality range, possibly indicating late hadronic interactions affecting the proton v2.

Azimuthal Anisotropy in U+U and Au+Au Collisions at RHIC.

Collisions between prolate uranium nuclei are used to study how particle production and azimuthal anisotropies depend on initial geometry in heavy-ion collisions. We report the two- and four-particle cumulants, v_{2}{2} and v_{2}{4}, for charged hadrons from U+U collisions at sqrt[s_{NN}]=193 GeV and Au+Au collisions at sqrt[s_{NN}]=200 GeV. Nearly fully overlapping collisions are selected based on the energy deposited by spectators in zero degree calorimeters (ZDCs). Within this sample, the observed dependence of v_{2}{2} on multiplicity demonstrates that ZDC information combined with multiplicity can preferentially select different overlap configurations in U+U collisions. We also show that v_{2} vs multiplicity can be better described by models, such as gluon saturation or quark participant models, that eliminate the dependence of the multiplicity on the number of binary nucleon-nucleon collisions.

Observation of Transverse Spin-Dependent Azimuthal Correlations of Charged Pion Pairs in p

We report the observation of transverse polarization-dependent azimuthal correlations in charged pion pair production with the STAR experiment in p^{↑}+p collisions at RHIC. These correlations directly probe quark transversity distributions. We measure signals in excess of 5 standard deviations at high transverse momenta, at high pseudorapidities η>0.5, and for pair masses around the mass of the ρ meson. This is the first direct transversity measurement in p+p collisions.

Observation of Charge Asymmetry Dependence of Pion Elliptic Flow and the Possible Chiral Magnetic Wave in Heavy-Ion Collisions.

We present measurements of π(-) and π(+) elliptic flow, v(2), at midrapidity in Au+Au collisions at √[s(NN)]=200, 62.4, 39, 27, 19.6, 11.5, and 7.7 GeV, as a function of event-by-event charge asymmetry, A(ch), based on data from the STAR experiment at RHIC. We find that π(-) (π(+)) elliptic flow linearly increases (decreases) with charge asymmetry for most centrality bins at √[s(NN)]=27 GeV and higher. At √[s(NN)]=200 GeV, the slope of the difference of v(2) between π(-) and π(+) as a function of A(ch) exhibits a centrality dependence, which is qualitatively similar to calculations that incorporate a chiral magnetic wave effect. Similar centrality dependence is also observed at lower energies.

Systemic therapy in men with metastatic castration-resistant prostate cancer: a systematic review.

AIMS: Since 2004, docetaxel-based chemotherapy has been the standard of care for men with metastatic castration-resistant prostate cancer (mCRPC), but recently randomised controlled trials (RCTs) of novel agents have shown promise in extending overall survival. These trials have evaluated agents delivered before chemotherapy, to replace or supplement docetaxel, or addressed treatment options for men who have progressed on docetaxel therapy. This review was undertaken to determine which systemic therapies improve cancer- or patient-related outcomes in men with mCRPC. MATERIALS AND METHODS: Searches were carried out in MEDLINE, EMBASE, the Cochrane Library and relevant conference proceedings. Eligible articles included RCTs comparing systemic therapy or combination (excluding primary or secondary androgen deprivation therapy, bone protective agents or radionuclides) with placebo or other agents in men with mCRPC. RESULTS: Twenty-five RCTs met the selection criteria. In chemotherapy-naive patients, targeted therapy with tasquinimod conferred a benefit in progression-free survival. Immunotherapy with sipuleucel-T extended overall survival and was well tolerated, but had no effect on the time to disease progression. Hypercastration with abiraterone extended progression-free survival, whereas overall survival was improved but not statistically proven. In the chemotherapy setting, updated and new trials of docetaxel alone confirmed the survival benefit seen in previous studies. A survival benefit with the addition of estramustine to docetaxel shown in a previous study did not lead to an improvement in pain palliation or quality of life. Trials of combining targeted therapies with docetaxel generally did not extend survival. The addition of bevacizumab improved progression-free survival, but not overall survival. The addition of GVAX immunotherapy or calcitriol was harmful. In the post-chemotherapy setting, progression-free and overall survival benefits were detected with cabazitaxel, abiraterone and enzalutamide. Cabazitaxel was associated with greater toxicity, whereas abiraterone and enzalutamide had less severe adverse effects. Satraplatin and sunitinib both extended progression-free survival, but did not improve overall survival. CONCLUSION: Docetaxel-based chemotherapy remains the standard of care in men with mCRPC who are candidates for palliative systemic therapy. Promising results are emerging with sipuleucel-T and abiraterone in the pre-docetaxel setting and cabazitaxel, abiraterone and enzalutamide in patients who progress on or after docetaxel. Further research to determine the optimal choice, sequence or even the combination of these agents is necessary.

Evidence-based guideline recommendations on the use of positron emission tomography imaging in head and neck cancer.

AIMS: To provide evidence-based practice guideline recommendations on the use of fluoro-2-deoxy-D-glucose positron emission tomography (PET) for diagnosis, staging and assessing treatment response, restaging or recurrence of head and neck cancer. MATERIALS AND METHODS: A systematic review by Facey et al. (Health Technology Assessment 2007;11(44):iii-iv, xi-267) was used as the evidence base for recommendation development. As the review was limited to August 2005, the evidence base was updated to July 2011 using the same search strategies for MEDLINE and EMBASE used in the original review. The authors of the current systematic review drafted recommendations, which were reviewed, adapted and accepted by consensus by the Ontario provincial Head and Neck Disease Site Group and a special meeting of clinical experts. RESULTS: The results of the Facey et al. review for head and neck cancer included five other systematic reviews and 31 primary studies. The 2005 to 2011 update search included four additional systematic reviews and 53 primary studies. Recommendations were developed based on this evidence and accepted by consensus. CONCLUSIONS: PET is recommended in the M and bilateral nodal staging of all patients with head and neck squamous cell carcinoma where conventional imaging is equivocal, or where treatment may be significantly modified. PET is recommended in all patients after conventional imaging and in addition to, or prior to, diagnostic panendoscopy where the primary site is unknown. PET is recommended for the staging and assessment of recurrence of patients with nasopharyngeal carcinoma if conventional imaging is equivocal. PET is recommended for restaging patients who are being considered for major salvage treatment, including neck dissection.

Evidence-based guideline recommendations on the use of positron emission tomography imaging in oesophageal cancer.

AIMS: To provide evidence-based practice guideline recommendations on the use of fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) for diagnosis, staging, assessing treatment response, liver metastasis and restaging or recurrence of oesophageal cancer. MATERIALS AND METHODS: A systematic review by Facey et al. (Health Technology Assessment 2007;11(44):iii-iv, xi-267) was used as the evidence base for recommendation development. As the review was limited to August 2005, the evidence base was updated to May 2010 using the same search strategies for MEDLINE and EMBASE used in the original review. The authors of the current systematic review drafted recommendations, which were reviewed, adapted and accepted by consensus by the Ontario provincial Gastrointestinal Disease Site Group and a special meeting of clinical experts. RESULTS: The results from the Facey et al. review for oesophageal cancer included four other systematic reviews and six primary studies. The 2005 to 2010 updated search included two additional systematic reviews and 29 primary studies. Recommendations were developed based on this evidence and accepted by consensus. CONCLUSIONS: PET is recommended to improve the accuracy of M staging for the staging work-up of patients with oesophageal cancer who are potential candidates for curative therapy. Due to insufficient evidence, no recommendation was made for or against the use of PET for the assessment of treatment response and the evaluation of suspected recurrence.

Evidence-based guideline recommendations on the use of positron emission tomography imaging in colorectal cancer.

AIMS: To provide evidence-based practice guideline recommendations on the use of fluoro-2-deoxy-d-glucose positron emission tomography (PET) for diagnosis, staging, assessing treatment response, liver metastasis and restaging or recurrence of colorectal cancer. MATERIALS AND METHODS: A systematic review by Facey et al. (Health Technology Assessment 2007;11(44):iii-iv, xi-267) was used as the evidence base for recommendation development. As the review was limited to August 2005, the evidence base was updated to May 2010 using the same search strategies for MEDLINE and EMBASE used in the original review. The authors of the current systematic review drafted recommendations, which were reviewed, adapted and accepted by consensus by the Ontario provincial Gastrointestinal Disease Site Group and a special meeting of clinical experts. RESULTS: The results from the Facey et al. review for colorectal cancer included three other systematic reviews and 24 primary studies. The 2005 to 2010 updated search included 10 additional systematic reviews and 28 primary studies. Recommendations were developed based on this evidence and accepted by consensus. CONCLUSIONS: The routine use of PET is not recommended for the diagnosis or staging of clinical stage I-III colorectal cancers. PET is recommended for determining management and prognosis if conventional imaging is equivocal for the presence of metastatic disease. PET is also not recommended for routine surveillance in patients with colorectal cancer treated with curative surgery at high risk for recurrence. It is recommended to determine the site of recurrence in the setting of rising CEA when conventional work-up fails to unequivocally identify metastatic disease. Finally, PET is recommended in the preoperative assessment of colorectal cancer liver metastasis before surgical resection.