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The purpose of this study was to determine the negative predictive value (NPV) of a 12- to 14-wk posttreatment PET/CT for 2-y progression-free survival (PFS) and locoregional control (LRC) in patients with p16-positive locoregionally advanced oropharyngeal cancer (LA-OPC). Study was a secondary endpoint in NRG-HN002, a noncomparative phase II trial in p16-positive LA-OPC, stage T1-T2, N1-N2b or T3, N0-N2b, and ≤10 pack-year smoking. Patients were randomized in a 1:1 ratio to reduced-dose intensity-modulated radiotherapy (IMRT) with or without cisplatin. Methods: PET/CT scans were reviewed centrally. Tumor response evaluations for the primary site, right neck, and left neck were performed using a 5-point ordinal scale (Hopkins criteria). Overall scores were then assigned as negative, positive, or indeterminate. Patients with a negative score for all 3 evaluation sites were given an overall score of negative. The hypotheses were NPV for PFS and LRC at 2-y posttreatment ≤ 90% versus >90% (1-sided P value, 0.10). Results: A total of 316 patients were enrolled, of whom 306 were randomized and eligible. Of these, 131 (42.8%) patients consented to a posttherapy PET/CT, and 117 (89.3%) patients were eligible for PET/CT analysis. The median time from the end of treatment to PET/CT scan was 94 d (range, 52-139 d). Estimated 2-y PFS and LRC rates in the analysis subgroup were 91.3% (95% CI, 84.6, 95.8%) and 93.8% (95% CI, 87.6, 97.5%), respectively. Posttreatment scans were negative for residual tumor for 115 patients (98.3%) and positive for 2 patients (1.7%). NPV for 2-y PFS was 92.0% (90% lower confidence bound [LCB] 87.7%; P = 0.30) and for LRC was 94.5% (90% LCB 90.6%; P = 0.07). Conclusion: In the context of deintensification with reduced-dose radiation, the NPV of a 12- to 14-wk posttherapy PET/CT for 2-y LRC is estimated to be >90%, similar to that reported for patients receiving standard chemoradiation. However, there is insufficient evidence to conclude that the NPV is >90% for PFS.

PurposeReducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven.Patients and methodsIn this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI).ResultsThree hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% (P = .04). For IMRT, 2-year PFS was 87.6% (P = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% v 52.4%; P < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% (P = .56).ConclusionThe IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.

PurposeBecause of the unprecedented disruption of health care services caused by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC) in a time of limited resources and heightened risk for patients and staff.Methods and materialsA panel of international experts from ASTRO, ESTRO, and select Asia-Pacific countries completed a modified rapid Delphi process. Topics and questions were presented to the group, and subsequent questions were developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios, early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated. The panel developed treatment recommendations for 5 HNC cases.ResultsIn total, 29 of 31 of those invited (94%) accepted, and after a replacement 30 of 30 completed all 3 surveys (100% response rate). There was agreement or strong agreement across a number of practice areas, including treatment prioritization, whether to delay initiation or interrupt radiation therapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care.ConclusionsThis urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit.

Radiation therapy (RT) consensus contouring guidelines in the postoperative setting for complex cutaneous squamous cell carcinoma of the head and neck have been developed by expert clinicians in the field of head and neck and dermato-oncology and members of the Head and Neck Cancer International Group to assist radiation oncologists involved in the management of this disease. These guidelines present a set of principles used to define postoperative RT volumes and corresponding minimum doses after resection of all macroscopic tumor with or without microscopic residual disease. It is anticipated they will promote the harmonization of postoperative RT globally and contribute to a reduction in treatment variation among clinicians, allowing for RT quality and outcomes assessment across institutions.

PurposeBecause of the unprecedented disruption of health care services caused by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC) in a time of limited resources and heightened risk for patients and staff.Methods and materialsA panel of international experts from ASTRO, ESTRO, and select Asia-Pacific countries completed a modified rapid Delphi process. Topics and questions were presented to the group, and subsequent questions were developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios, early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated. The panel developed treatment recommendations for 5 HNC cases.ResultsIn total, 29 of 31 of those invited (94%) accepted, and after a replacement 30 of 30 completed all 3 surveys (100% response rate). There was agreement or strong agreement across a number of practice areas, including treatment prioritization, whether to delay initiation or interrupt radiation therapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care.ConclusionsThis urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit.

Background: The causes for delays during the COVID19 pandemic and their impact on head and neck cancer (HNC) diagnosis and staging are not well described. Methods: Two cohorts were defined a priori for review and analysis—a Pre‐Pandemic cohort (June 1 to December 31, 2019) and a Pandemic cohort (June 1 to December 31, 2020). Delays were categorized as COVID‐19 related or not, and as clinician, patient, or policy related. Results: A total of 638 HNC patients were identified including 327 in the Pre‐Pandemic Cohort and 311 in the Pandemic Cohort. Patients in the Pandemic cohort had more N2‐N3 category (41% vs. 33%, p = 0.03), T3‐T4 category (63% vs. 50%, p = 0.002), and stage III‐IV (71% vs. 58%, p < 0.001) disease. Several intervals in the diagnosis to treatment pathway were significantly longer in the pandemic cohort as compared to the Pre‐Pandemic cohort. Among the pandemic cohort, 146 (47%) experienced a delay, with 112 related to the COVID‐19 pandemic; 80 (71%) were clinician related, 15 (13%) were patient related, and 17 (15%) were policy related. Conclusions: Patients in the Pandemic cohort had higher stage disease at diagnosis and longer intervals along the diagnostic pathway, with COVID‐19 related clinician factors being the most common cause of delay. [ABSTRACT FROM AUTHOR]

Understanding the socioecological contexts of gay men living with HIV is critical to addressing the environmental conditions that influence their lifetime experiences of housing insecurity and homelessness. In line with the strategies of the US Center for Disease Control and Prevention to end the HIV epidemic, it is of utmost importance to recognize how the allocation of available resources impacts health inequities affecting gay men living with HIV who experience housing insecurity and homelessness. Drawing from the World Health Organization's social determinants of health (SDoH) framework, we used an exploratory, community-based research (CBR) approach to examine the lifetime experiences and important sources of support of gay men living with HIV at midlife who have experienced housing insecurity in Southern Nevada. Thematic analysis of our semi-structured interviews with 12 gay men living with HIV at midlife revealed three overarching themes: (1) challenges to obtaining housing and related support, (2) informal support from friends, and (3) formal support from community-based sources employing diverse support strategies. In this article, we discuss the different sub-themes we identified under these overarching themes and the implications of our findings from an SDoH perspective. We conclude with a discussion on the dire need to (1) highlight the considerable value of both informal and formal sources of support for the housing insecure, and (2) generate recommendations for interventions to address housing insecurity and homelessness with greater consideration for the impacts of SDoH in the work dedicated to helping gay men living with HIV at midlife overcome housing insecurity as they age. [ABSTRACT FROM AUTHOR]

Many geoscience educators have noted the difficulty that students experience in transferring their classroom knowledge to the field environment. The Geoscience Garden, on the University of Alberta North Campus, provides a simulated field environment in which Earth Science students can develop field observation skills, interpret features of Earth's crust in three dimensions, and discover Earth history. The garden consists of large (1-5 m) boulders and rock slabs arranged in a landscaped layout that represents the geology of western and northern Canada. The project adds a unique capability for teaching basic field skills to students in a local environment and prepares them for field courses at more remote locations. Students work in the garden in a second-year introductory structural geology class that precedes a field school. Student perceptions of the effectiveness of the installation were evaluated using surveys of students returning from field school. Initial responses were positive; students returning from field school after the introduction of the garden reported significantly greater satisfaction with their ability to collect field data.

The ca. 355 Ma Fountain Lake Group in the Cobequid Highlands of Nova Scotia, is part of the transtensional basin fill that formed during dextral strike-slip motion between Avalonia and the Meguma terranes following the Acadian Orogeny. Paleomagnetic analysis of the Fountain Lake Group offers a paleolatitude estimate for the Laurentian accretionary margin in the Early Carboniferous as well as locality-specific paleomagnetic directions, which indicate clockwise-sense block rotations during dextral strike-slip motion along the Cobequid Fault zone. Stepwise demagnetization of 142 specimens from 20 sites in three Fountain Lake Group localities across the Cobequid Highlands (Squally Point, West Moose River, and Wentworth exposures) reveals remanence consisting of an easily removed component of probable recent origin, and more persistent components carried by magnetite and hematite, which in petrographic and electron beam analysis appear to be of primary igneous and volcanic oxidation origins, respectively. Sites from all three localities carry stable characteristic remanent magnetization (ChRM) directions that assume similar moderate downward inclinations when tilt-corrected. A Block Rotation Fisher analysis inclination-only fold test demonstrated best agreement at 90% unfolding, showing that remanence acquisition pre-dates Alleghenian deformation in the Late Carboniferous and is most likely of primary 355 Ma age. Paleomagnetic results for the Squally Point, West Moose River, and Wentworth localities show relative rotations between the blocks that are variously clockwise-rotated compared with a Laurentia cratonic reference frame. Inclinations at all three localities imply a subtropics paleolatitude for the margin (at Squally Point, 27.2[degrees] [+ or -] 9.4[degrees]; N = 7 sites), directly supporting the depicted location of Laurentia and its Appalachian accretionary margin in most Devonian to Early Carboniferous reconstructions. Key words: Avalonia, tectonic rotation, Appalachian, Laurentia, paleolatitude, Meguma terrane. Le Groupe de Fountain Lake d'environ 355 Ma des terres hautes de Cobequid, en Nouvelle-Ecosse, fait partie des depots de remplissage du bassin de transtension qui s'est forme durant le coulissage dextre des terranes dAvalonie et de Meguma l 'un par rapport a l'autre apres l'orogenese acadienne. L'analyse paleomagnetique du Groupe du Fountain Lake fournit une estimation de la paleolatitude de la marge accretionnaire laurentienne au Carbonifere precoce et des directions paleomagnetiques pour differentes localites qui indiquent des rotations horaires de blocs durant le coulissage dextre le long de la zone de la faille de Cobequid. La desaimantation par etapes de 142 specimens provenant de 20 sites dans trois localites du Groupe de Fountain Lake dans les terres hautes de Cobequid (affleurements de Squally Point, West Moose River et Wentworth) revele une remanence consistant en une composante facile a enlever probablement d'origine recente et des composantes plus persistantes portees par la magnetite et l'hematite qui, selon les analyses petrographiques et a faisceau electronique, semblent respectivement etre de source ignee primaire et avoir ete formee par oxydation volcanique. Des sites dans les trois localites presentent des directions d'aimantation remanente caracteristique (MRCh) stables qui, apres correction pour l'inclinaison, indiquent des plongees moderees semblables. Un essai de plissement integrant seulement l'inclinaison jumele a l'analyse de rotation de blocs de Fisher demontre une bonne concordance pour un depliage de 90 %, ce qui montre que l 'acquisition de la remanence est anterieure a la deformation alleghanienne au Carbonifere tardif et que son age primaire est fort probablement de 355 Ma. Les resultats paleomagnetiques pour les localites de Squally Point, West Moose River et Wentworth montrent des rotations relatives entre les blocs, qui presentent une rotation horaire variable par rapport au cadre de reference du craton laurentien. Les inclinaisons dans les trois localites indiqueraient une paleolatitude subtropicale pour la marge (a Squally Point, 27,2[degrees] [+ or -] 9,4[degrees]; N = 7 sites), ce qui appuie directement l'emplacement indique de la Laurentie et de sa marge accretionnaire appalachienne dans la plupart des reconstitutions pour l'intervalle du Devonien au Carbonifere precoce. [Traduit par la Redaction] Mots-cles: Avalonie, rotation tectonique, Appalaches, Laurentie, paleolatitude, terrane de Meguma., Introduction The amalgamation of Pangea marks the assembly of the most recent, and best-known supercontinent in Earth history. The final stages of Pangea assembly took place in the late Paleozoic [...]

Paleomagnetic results and a U--Pb baddeleyite age from the Silurian Mavillette gabbroic sill in southwest Nova Scotia, Canada, provide new evidence about the Paleozoic tectonic evolution of the Meguma terrane. The Mavillette gabbro sill intruded ca. 440-430 Myr old bimodal rift-related metavolcanic and metasedimentary rocks of the White Rock Formation in the Silurian--Devonian Rockville Notch Group. The 426.4 [+ or -] 2.0 Ma Mavillette gabbro age is notably younger than the ca. 440 Ma magmatism, but is part of a geochemically defined suite of within-plate sills and volcanic rocks of the Rockville Notch Group with ages as young as Early Devonian. Paleomagnetic investigation of 13 sites distributed along the Neoacadian (ca. 390 Ma) synclinal limbs of the Mavillette sill reveal magnetization directions that fail a fold test and therefore postdate Silurian emplacement of the gabbro. The post-folding remanence has a mean direction of D = 153.4, I = 17.1[degrees]; [[alpha].sub.95] = 6.5[degrees] (n = 12 sites), with corresponding paleopole 31.9 [degrees]S, 325.2 E; dp = 3.5[degrees], dm = 6.7[degrees] that resembles a pervasive late Carboniferous Kiaman overprint magnetization in North America, but is rotated significantly 22.2[degrees] [+ or -] 8.1[degrees] counter-clockwise (CCW). Mavillette remanence acquisition likely occurred in concert with fluid mobilization related to Alleghanian deformation, recorded locally by ca. 320 Ma muscovite [.sup.40][Ar.sup.-39] Ar ages. Previously published paleomagnetic results from the Meguma terrane also have Carboniferous remanence directions with similar ~24[degrees] CCW discordance. The regional CCW rotation of the southwest Meguma terrane post-dates this ca. 320 Ma tectonothermal remanence acquisition event, likely recording the development of an oroclinal bend of the Meguma terrane during the Alleghanian orogeny. Key words: rift magmatism, terrane accretion, tectonic rotation, Appalachian, overprint magnetization, Meguma orocline, faunal associations.. Les resultats d'analyses paleomagnetiques et un age U-Pb sur baddeleyite du filon-couche gabbroique silurien de Mavillette, dans le sud-ouest de la Nouvelle-Ecosse, Canada, fournissent de nouveaux renseignements sur l'evolution tectonique paleozoique du terrane de Meguma. Le filon-couche gabbro'ique de Mavillette s'est mis en place dans des roches metasedimentaires et metavolcaniques bimodales associees au rifting formees vers 440-430 Ma, de la Formation de White Rock, dans le Groupe siluro-devonien de Rockville Notch. L'age de 426,4 [+ or -] 2,0 Ma du gabbro de Mavillette est sensiblement plus jeune que le magmatisme vers 440 Ma, mais fait partie d'une serie definie par la geochimie de filons-couches et de roches volcaniques intraplaques du Groupe de Rockville Notch, dont les ages vont jusqu'au Devonien precoce. L'etude paleomagnetique de 13 sites repartis le long des flancs du synclinal neoacadien (vers 390 Ma) du filon-couche de Mavillette revele des directions de magnetisation qui echouent une epreuve de plissement et doivent donc etre posterieures a la mise en place du gabbro au Silurien. La remanence post-plissement a une direction moyenne de D = 153,4, I = 17,1[degrees]; [[alpha].sub.95] = 6,5[degrees] (n = 12 sites), avec un paleopole correspondant a 31,9[degrees]S, 325,2E; dp = 3,5[degrees], dm = 6,7[degrees] qui ressemble a une magnetisation penetrante superposee de Kiaman, d'age carbonifere tardif, en Amerique du Nord, mais caracterisee par une rotation antihoraire (AH) significative de 22,2[degrees] 6 8,1[degrees]. L'acquisition de la remanence de Mavillette s'est produite de concert avec la mobilisation de fluides associee a la deformation alleghanienne, dont temoignent localement des ages [.sup.40][Ar.sup.-39]Ar sur muscovite d'environ 320 Ma. Des resultats d'analyses paleomagnetiques publies precedemment pour le terrane de Meguma montrent aussi des directions de remanence carboniferes presentant une discordance semblable de ~24[degrees] AH. La rotation AH regionale du sud-ouest du terrane de Meguma est posterieure a cet episode d'acquisition de remanence tectonothermique, temoignant vraisemblablement du developpement d'une flexion oroclinale du terrane de Meguma durant l'orogenese alleghanienne. [Traduit par la Redaction] Mots-cles : magmatisme de rifting, accretion de terranes, rotation tectonique, Appalaches, magnetisation superposee, oroclinal de Meguma, associations fauniques.., Introduction The Meguma terrane is exposed in the southern half of mainland Nova Scotia (Fig. 1), Canada, and related rocks constituting a larger 'Megumia' (Waldron et al. 2011) also underlie [...]

PurposeDespite significant improvement in locoregional control in the contemporary era of nasopharyngeal carcinoma (NPC) treatment, patients still suffer from a significant risk of distant metastasis (DM). Identifying those patients at risk of DM would aid in personalized treatment in the future. MicroRNAs (miRNAs) play many important roles in human cancers; hence, we proceeded to address the primary hypothesis that there is a miRNA expression signature capable of predicting DM for NPC patients.Methods and resultsThe expression of 734 miRNAs was measured in 125 (Training) and 121 (Validation) clinically annotated NPC diagnostic biopsy samples. A 4-miRNA expression signature associated with risk of developing DM was identified by fitting a penalized Cox Proportion Hazard regression model to the Training data set (HR 8.25; p < 0.001), and subsequently validated in an independent Validation set (HR 3.2; p = 0.01). Pathway enrichment analysis indicated that the targets of miRNAs associated with DM appear to be converging on cell-cycle pathways.ConclusionsThis 4-miRNA signature adds to the prognostic value of the current "gold standard" of TNM staging. In-depth interrogation of these 4-miRNAs will provide important biological insights that could facilitate the discovery and development of novel molecularly targeted therapies to improve outcome for future NPC patients.