A case of abnormally dilated and tortuous arc of Buhler and pancreaticoduodenal arteries in the absence of celiac trunk stenosis.

INTRODUCTION: The Arc of Buhler is a rare vascular variant describing a persistent remnant of the embryologic ventral anastomosis between the celiac trunk (CT) and superior mesenteric artery (SMA), invariably reported in the context of CT stenosis. PURPOSE: To report a case of (1) a large and tortuous pancreaticoduodenal arcade and (2) a large and tortuous Arc of Buhler in the absence of celiac axis stenosis. METHODS: The variant was discovered during routine cadaver dissection. We acquired transverse biopsies of variant vessels and evaluated their wall thickness. RESULTS: The donor's anterior PDA, posterior PDA, and Arc of Buhler had larger diameters, and the common hepatic artery had a smaller diameter than the literature-reported values of a standard human body. The posterior PDA had significantly increased wall thickness compared to the other investigated vessels. CONCLUSIONS: The Arc of Buhler is a rare remnant of the embryologic ventral anastomosis that is estimated to be hemodynamically active in only half of cases. Previous reports have documented hemodynamically active Arcs of Buhler only in cases of CT stenosis. To the best of the authors' knowledge, this is a unique case of a persistent and hemodynamically active Arc of Buhler in the absence of CT stenosis. Clinicians should be aware of this variant as its abnormal position may increase risk of herniation and surgical complications, and its tortuosity may increase risk of clot formation.

[Burnout syndrome: definition, typology and management]. / Le syndrome d'épuisement professionnel : définition, typologie et prise en charge.

Although burnout syndrome was first described clinically about sixty years ago, it hasn't yet found its place in the classification of mental disorders. The wide range of clinical signs and aetiopathogenic theories has certainly contributed to this situation. There are different clinical forms of burnout and various therapeutic strategies. Psychiatrists play a key role in the multidisciplinary diagnosis of burnout.

Expression, purification and kinetic characterisation of human tissue transglutaminase.

The expression of soluble recombinant transglutaminase (TGase) has proven to be a challenge for many research groups. Herein, we report a complementary method for the expression, in BL21(DE3) Escherichia coli, of recombinant human tissue transglutaminase (hTG2) whose solubility is enhanced through N-terminal fusion to glutathione S-transferase (GST). Moreover, we report the cleavage of the GST tag using PreScission™ Protease (PSP) and purification of hTG2 in its untagged form, distinctively suitable for subsequent studies of its remarkable conformational equilibrium. The effects of co-solvents and storage conditions on stability of purified hTG2 are also reported. Furthermore, we demonstrate for the first time the use of a convenient chromogenic assay to measure the activity of the human enzyme. The utility of this assay was demonstrated in the measurement of the kinetic parameters of a wide variety of substrates and inhibitors of both hTG2 and the extensively studied guinea pig liver TGase. Finally, comparison of these results provides further evidence for the functional similarity of the two enzymes.

Adjuvant treatment for endometrial cancer: literature review and recommendations by the Comité de l'évolution des pratiques en oncologie (CEPO).

OBJECTIVE: Despite the very good prognosis of endometrial cancer, a number of patients with localized disease relapse following surgery. Therefore, various adjuvant therapeutic approaches have been studied. The objective of this review is to evaluate the efficacy and safety of neoadjuvant and adjuvant therapies in patients with resectable endometrial cancer and to develop evidence-based recommendations. METHODS: A review of the scientific literature published between January 1990 and June 2012 was performed. The search was limited to published phase III clinical trials and meta-analyses evaluating the efficacy of neoadjuvant or adjuvant therapies in patients with endometrial carcinoma or carcinosarcoma. A total of 23 studies and five meta-analyses were identified. RESULTS: The selected literature showed that in patients with a low risk of recurrence, post-surgical observation is safe and recommended in most cases. There are several therapeutic modalities available for treatment of endometrial cancers with higher risk of recurrence, including vaginal brachytherapy, external beam radiotherapy, chemotherapy, or a combination of these. CONCLUSIONS: Considering the evidence available to date, the CEPO recommends the following: (1)post-surgical observation for most patients with a low recurrence risk; (2)adjuvant vaginal brachytherapy for patients with an intermediate recurrence risk; (3)adjuvant pelvic radiotherapy with or without vaginal brachytherapy for patients with a high recurrence risk; addition of adjuvant chemotherapy may be considered as an option for selected patients (excellent functional status, no significant co-morbidities, poor prognostic factors); (4)adjuvant chemotherapy and pelvic radiotherapy with or without brachytherapy and para-aortic irradiation for patients with advanced disease;

Site-specific protein propargylation using tissue transglutaminase.

Transglutaminases (TGases) catalyse the transamidation of glutamine residues with primary amines. Herein we report the first FRET-based activity assay for the direct detection of the ligation (transamidation) reaction mediated by tissue TGase (TG2). This novel assay was then used in a microtiter plate-based screen of a library of 18 potential amine substrates. From this screen it was discovered that propargyl amine serves as an excellent substrate for TG2. Subsequently, propargyl amine and 2-azidoethyl amine were validated independently as TG2 substrates with K(M) values of 44 ± 4 µM, and 0.99 ± 0.06 mM, respectively. In a proof-of-principle protein labelling experiment, the protein casein was selectively functionalized with propargyl amine using TG2 and subsequently fluorescently labelled through a dipolar cycloaddition reaction with an azido-fluorescein conjugate. This application demonstrates the strong potential of using TG2 for site-specific protein modification through a combination of enzymatic and bioorthogonal chemistry.

Preferential association between childhood emotional abuse and bipolar disorder.

Childhood trauma has been suggested to be involved in the susceptibility to bipolar disorder. However, case-control studies are lacking, and the preferential implication and the dose-effect of different trauma subtypes remain poorly investigated. Two hundred six bipolar patients and 94 controls completed the Childhood Trauma Questionnaire (CTQ; Bernstein et al., 1994). The CTQ total score was higher for bipolar patients than for controls. The presence of multiple trauma was significantly more frequent in bipolar patients than in controls (63% vs. 33%). Multiple logistic regression suggested that only emotional abuse was associated with bipolar disorder with a suggestive dose-effect. Clinical practice should include systematic assessment of childhood trauma among bipolar patients with a particular focus on emotional abuse.

Photolabeling of tissue transglutaminase reveals the binding mode of potent cinnamoyl inhibitors.

We have recently developed a new class of cinnamoyl derivatives as potent tissue transglutaminase (TG2) inhibitors. Herein, we report the synthesis of a diazirine derivative of these inhibitors and its application to the photolabeling of its binding site on guinea pig liver transglutaminase. Two novel homology models were generated for this commonly studied TG2, which differ in the conformational state they represent. Tryptic digest and mass spectrometric analysis of the photolabeling experiment showed that only residue Cys230 was labeled, and our homology models were used to visualize these results. This visualization suggested that Cys230 is somewhat more solvent-exposed in the "closed" conformation of TG2, compared to the "open" conformation. Docking experiments suggested binding modes consistent with the labeling pattern that would block access to the tunnel leading to the active site, consistent with the observed mode of inhibition. However, while these modeling simulations favored the closed conformation as the target of our cinnamoyl inhibitors, native PAGE experiments indicated the open conformation of the enzyme in fact predominates in the presence of our photolabeling derivative. These results are important for understanding the binding modes of TG2 inhibitors in general and will be critical for the structure-based design of future inhibitors.

Blood pressure and burden of hypertension in Cameroon, a microcosm of Africa: a systematic review and meta-analysis of population-based studies.

OBJECTIVE: To estimate national and geography-based variations in blood pressure and burden of hypertension in Cameroon, generally called 'miniature Africa'. METHODS: PubMed, Medline, EMBASE, CINHAL, Web of Science, Popline, Scopus and BDSP were searched through November 2018, for hypertension studies among Cameroonians aged at least 18 years. Hypertension was measured as SBP at least 140 mmHg or DBP at least 90 mmHg. Random-effects meta-analysis was used. RESULTS: Twenty studies involving 46 491 participants met inclusion criteria. Overall hypertension prevalence was 30.9% [95% confidence interval (CI) 27.0-34.8]: 29.6% (24.1-35.1) and 32.1% (27.2-37.1) in 1994-2010 and 2011-2018, respectively. Of hypertensive participants, only 24.4% (18.9-30.0) - 31.6% (21.0-42.3) and 20.8% (14.0-27.7) in 1994-2010 and 2011-2018, respectively - were aware of their status, 15.1% (10.6-19.6) were taking antihypertensive medications and 8.8% (5.7-11.9) - 10.4% (7.5-13.3) and 8.3% (4.4-12.3) in 1994-2010 and 2011-2018, respectively - were controlled. Hypertension prevalence varied by sex: 34.3% (30.0-38.6) for men and 31.3% (26.5-36.1) for women; ethnicity: from 3.3% (0.4-6.2) among Pygmies to 56.6% (49.4-63.8) among Bamileke; urbanity: 25.4% (17.1-33.7) for rural and 31.4% (27.3-35.5) for urban dwellers; agroecological zone: from 35.1% (28.9-41.3) in Tropical highlands to 28% (20.1-35.9) in Guinea-Savannah; and subnational region: from 36.3% (27.8-44.9) in the West to 17.1% (9.9-44.2) in the South. CONCLUSION: Cameroon's hypertension prevalence is high and increasing whereas awareness, treatment and control are low and declining. Emerging patterns call urgently for effective campaigns to raise hypertension awareness alongside strategies for hypertension prevention and BP control.

Affective lability and affect intensity as core dimensions of bipolar disorders during euthymic period.

Bipolar disorders are usually defined by alternative mood states, but a more precise characterization of the euthymic period could provide further insights into the pathophysiology of bipolar disorders. Surprisingly, few studies have investigated core affective dimensions in euthymic bipolar patients. In this study, we assessed 179 euthymic bipolar patients (score<12 on the Montgomery-Asberg Depression Scale and a score<6 on the Bech-Rafaelsen Mania Scale) compared with 86 control subjects using French versions of the Affective Lability Scale (ALS) and the Affect Intensity Measure (AIM). Data were analyzed by logistic regression. Our results showed that euthymic bipolar subjects reported having more intense emotions than controls and also had a higher affective lability. High scores in both affective dimensions were associated with a significantly higher risk for psychiatric axis I comorbidity. Moreover, a high affective lability score was associated with an earlier age of onset for bipolar disease. Affective lability and affect intensity might be two core dimensions of bipolar disorder during euthymic periods, suggesting that bipolar disorder is not circumscribed to mood episodes but also affects emotional reactivity between episodes. Both dimensions could account for the stress reactivity of bipolar patients that may lead to relapses.

Handedness and schizotypal features in healthy subjects.

BACKGROUND: An excess of mixed-handedness has been repeatedly reported in schizophrenia and schizotypy. Handedness is a measure of atypical cerebral lateralization, which is considered as a risk factor for schizophrenia. Several studies have attempted to identify correlations between handedness and dimensions of psychosis but the results obtained so far remain inconclusive. OBJECTIVE: To explore a possible link between mixed-handedness and the three classical dimensions of psychosis. As speech and language disorders may be associated with cerebral lateralization, we predicted a correlation between mixed-handedness and disorganized dimension. METHODS: We used the Schizotypal Personality Questionnaire (SPQ) and the Edinburgh Handedness Inventory (EHI) to study the correlation between mixed-handedness scores and positive, negative or disorganized dimensions in a sample of 62 healthy subjects. RESULTS: We found a negative correlation between mixed-handedness and the disorganized dimension of schizotypy, as individuals with prominent mixed-handedness showed more severe disorganization. CONCLUSION: We have identified a link between mixed-handedness and the disorganized dimension that may help to identify genetic vulnerability factors involved in psychosis.

Executive deficits in psychotic and bipolar disorders - implications for our understanding of schizoaffective disorder.

OBJECTIVE: Schizoaffective disorder could be considered as a form of schizophrenia, a form of bipolar disorder, an independent disorder or a disorder intermediate between bipolar disorder and schizophrenia, within a psychotic continuum. The study of cognitive deficits in subjects with those diagnoses could help differentiate between these possibilities. METHODS: We compared cognitive performances of schizoaffective (SZAff) subjects with those of subjects with schizophrenia (SZ), bipolar disorder with psychotic symptoms (life-time) (BDP), bipolar disorder without life-time occurrence of psychotic symptoms (BD) and normal controls (NC). We used two tests of executive functions - the Wisconsin Card Sorting Test (WCST) and the Trail-making Test (TMT) - that are known to be impaired in those disorders. RESULTS: The number of perseverative errors on WCST was highest in SZ subjects and gradually decreased in SZAff, BDP and, finally in BD subjects. By contrast, SZ and SZAff subjects obtained similar scores in the TMT, as did BD and BDP patients. CONCLUSIONS: These results suggest that, for some deficits, there may be a continuum between SZ, SZAff and affective disorders, whereas SZAff patients most closely resemble SZ patients for other deficits. This implies that different conceptual views about schizoaffective disorder should be seen as complementary, rather than mutually exclusive.

Commodités familiales et santé des enfants de moins de cinq ans en Haïti.

OBJECTIFS: Évaluer le rôle des commodités familiales dans l'occurrence de la diarrhée chez les enfants de moins de 5 ans en Haïti, selon leur type (eau potable, toilettes et réfrigérateur) et leur nombre.MÉTHODE : Nous avons mis en commun les données de quatre Enquêtes démographiques et de santé réalisées en Haïti entre 1994-1995 et 2012. Nous avons retenu un échantillon de 14 481 enfants de 1-59 mois. Nous avons évalué le rôle des commodités familiales dans l'occurrence de la diarrhée selon le groupe d'âge d'enfants à risque (1-5; 6-11; 12-23; 24-59 mois), au moyen des modèles de régression logistique.RÉSULTATS : La prévalence de la diarrhée chez les enfants de 1-59 mois en Haïti est estimée à 29,31 %. Elle atteint 42,14 % chez les enfants de 6-11 mois. Elle est plus faible pour les enfants dont les familles ont accès à une eau potable améliorée, des toilettes améliorées ou un réfrigérateur. Elle est d'autant plus faible que les familles possèdent au moins deux commodités simultanément. Nous ne trouvons pas de différences significatives dans l'occurrence de la diarrhée infanto-juvénile selon l'accès à l'eau potable (p > 0,10). Prenant en compte l'effet de période, une occurrence réduite de la diarrhée est significativement associée aux toilettes améliorées chez les enfants de 24-59 mois (RC : 0,62; p < 0,05) et au réfrigérateur chez les 6-11 mois (RC : 0,11; p < 0,05). Pour le nombre de commodités, seuls les 24-59 mois ayant au moins deux commodités ont une occurrence de la diarrhée statistiquement inférieure de celle des plus défavorisés (RC : 0,45; p < 0,05). CONCLUSION: Augmenter l'accès aux commodités familiales et leur nombre par ménage demeure essentiel dans la lutte contre la diarrhée en Haïti. Une intervention intégrée serait donc à préconiser dans l'environnement sociosanitaire haïtien.

Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder.

BACKGROUND: Executive dysfunctions have been studied as a potential endophenotype associated with the genetic basis of autism. Given that recent findings from clinical and molecular genetic studies suggest that autism and obsessive-compulsive disorder (OCD) could share a common pattern of heritability, we assessed executive functions as a possible common cognitive endophenotype in unaffected family members of individuals with either autism or OCD. METHODS: Five tests assessing executive functions (Tower of London, verbal fluency, design fluency, trail making and association fluency) were proposed to 58 unaffected first-degree relatives (parents and siblings) of probands with autism and 64 unaffected first-degree relatives of OCD patients. Results were compared with those of 47 healthy controls matched for age, sex, and level of education. RESULTS: In the Tower of London test, both groups of unaffected relatives showed significantly lower scores and longer response times compared with controls. No differences were observed between autism and OCD relatives and healthy controls in the four other tasks (verbal fluency, design fluency, trail making test and association fluency). CONCLUSIONS: Our findings show the existence of executive dysfunction in the unaffected first-degree relatives of probands with OCD, similar to those observed in the relatives of patients with autism. These results support and extend previous cognitive studies on probands indicating executive dysfunctions in autism and OCD. Planning and working memory processes could thus represent a common cognitive endophenotype in autism and OCD that could help in the identification of genes conferring vulnerability to these disorders.

Limitations of Personalized Medicine and Gene Assays for Breast Cancer.

Adjuvant systemic treatments reduce the risk of breast cancer recurrence following the local treatment of primary stage I-III breast cancers. For patients with hormone-positive breast cancers receiving hormonal therapy, the risk of distant recurrence is under 20% and therefore, many patients may potentially be spared of chemotherapy. Consequently, several molecular signatures based on gene expression were developed to better determine which breast cancer patients would benefit from chemotherapy. We present the case of a 62-year-old woman diagnosed with an early stage hormone receptor-positive breast cancer that was treated with a partial mastectomy. Oncotype DX (Genomic Health, Redwood City, CA) molecular testing was performed on the surgical specimen, which reported a recurrence score of 0. The patient commenced adjuvant radiotherapy during which she developed symptoms suggestive of bone metastasis and was subsequently diagnosed with a spinal cord compression that required neurosurgery and radiotherapy. Pathology review of the specimen from the spine surgery revealed a metastatic breast carcinoma with neuroendocrine differentiation. Molecular assays such as Oncotype DX are increasingly used to prognosticate patient outcomes and help determine who may avoid chemotherapy. This case report seeks to illustrate that such assays should not be used in the presence of rare histological subtypes like neuroendocrine breast cancers, which are often under-reported. The current status of personalized medicine and gene assays in breast cancer is reviewed and potential strategies are suggested to identify these rare cases to better orient diagnostic and treatment decisions.

Radiation therapy quality indicators for invasive breast cancer.

BACKGROUND AND PURPOSE: Radiation therapy (RT) for breast cancer has evolved considerably over the past two decades. A concise list of optimal care indexes is lacking. The purpose of this project was to generate a suite of quality of care indicators for breast cancer RT. MATERIALS AND METHODS: A modified Delphi approach was used including a comprehensive literature and guideline review (1995-2015), an initial review of potential quality indicators (QIs) by a steering committee, a survey of Canadian Radiation Oncologists, and a face-to-face consensus development meeting with breast cancer experts to develop a list of breast RT quality indicators. RESULTS: The literature review identified 163 potential QIs, which was reduced to 73 by the steering committee. After all rounds of the Delphi process the final suite included 33 QIs. Of these, 28 (85%) received at least 80% acceptance from the Radiation Oncologists who participated in the final online survey. CONCLUSIONS: A suite of measureable RT quality indicators to be considered during management of invasive breast cancer was developed. These indicators could be used to assess the quality and consistency of breast cancer RT practices.

Development of new scaffolds as reversible tissue transglutaminase inhibitors, with improved potency or resistance to glutathione addition.

Previous studies within our group have yielded a class of cinnamoyl-based competitive reversible inhibitors for tissue transglutaminase (TG2), with Ki values as low as 1.0 µM (compound CP4d). However, due to the electrophilic nature of their alkene moiety, this class of inhibitors is susceptible to nucleophilic attack by glutathione, a key element in cellular metabolism and toxicity response. To address this issue, we made several modifications to the inhibitor scaffold, ultimately showing that a bis(triazole) scaffold increased resistance to nucleophilic attack, with compound 27d being the most potent (Ki = 10 µM). In the process of reducing reactivity, we also prepared a new class of inhibitors, replacing the alkene of CP4d with an alkyne, leading to a significant increase in potency for compound 22b (Ki = 420 nM).

Familial resemblance for executive functions in families of schizophrenic and bipolar patients.

Executive dysfunctions are considered to be putative markers of familial/genetic vulnerability to both schizophrenia and bipolar disorder. However, familial resemblance must be demonstrated before executive functions are used as a potential endophenotype. The aim of this study was to investigate familial resemblance for executive functions in families of schizophrenic and bipolar subjects. We assessed executive functions by means of two tests - the Wisconsin Card Sorting Test (WCST) and the Trail Making Test (TMT) - in 351 subjects from five populations: schizophrenic patients, bipolar patients, a group of relatives for each patient group and controls. For both tests, cognitive assessment results were consistent with previous studies: schizophrenic patients showed the greatest impairment, followed by bipolar patients and then the two groups of relatives. In families of bipolar patients we observed familial resemblance for the WCST and part A and part B of the TMT. However, by contrast with the classical point of view, considering executive measures to be markers of genetic vulnerability to schizophrenia, we did not demonstrate familial resemblance for either of the two executive tests in families of schizophrenic patients. Thus, executive measures, as assessed by the WCST or the TMT, should not be used as endophenotypes in genetic studies of schizophrenia unless confounders are identified and their effects eliminated.

Vascular Smooth Muscle Sirtuin-1 Protects Against Diet-Induced Aortic Stiffness.

Arterial stiffness, a major cardiovascular risk factor, develops within 2 months in mice fed a high-fat, high-sucrose (HFHS) diet, serving as a model of human metabolic syndrome, and it is associated with activation of proinflammatory and oxidant pathways in vascular smooth muscle (VSM) cells. Sirtuin-1 (SirT1) is an NAD(+)-dependent deacetylase regulated by the cellular metabolic status. Our goal was to study the effects of VSM SirT1 on arterial stiffness in the context of diet-induced metabolic syndrome. Overnight fasting acutely decreased arterial stiffness, measured in vivo by pulse wave velocity, in mice fed HFHS for 2 or 8 months, but not in mice lacking SirT1 in VSM (SMKO). Similarly, VSM-specific genetic SirT1 overexpression (SMTG) prevented pulse wave velocity increases induced by HFHS feeding, during 8 months. Administration of resveratrol or S17834, 2 polyphenolic compounds known to activate SirT1, prevented HFHS-induced arterial stiffness and were mimicked by global SirT1 overexpression (SirT1 bacterial artificial chromosome overexpressor), without evident metabolic improvements. In addition, HFHS-induced pulse wave velocity increases were reversed by 1-week treatment with a specific, small molecule SirT1 activator (SRT1720). These beneficial effects of pharmacological or genetic SirT1 activation, against HFHS-induced arterial stiffness, were associated with a decrease in nuclear factor kappa light chain enhancer of activated B cells (NFκB) activation and vascular cell adhesion molecule (VCAM-1) and p47phox protein expressions, in aorta and VSM cells. In conclusion, VSM SirT1 activation decreases arterial stiffness in the setting of obesity by stimulating anti-inflammatory and antioxidant pathways in the aorta. SirT1 activators may represent a novel therapeutic approach to prevent arterial stiffness and associated cardiovascular complications in overweight/obese individuals with metabolic syndrome.

Analysis of quantitative trait loci for behavioral laterality in mice.

Laterality is believed to have genetic components, as has been deduced from family studies in humans and responses to artificial selection in mice, but these genetic components are unknown and the underlying physiological mechanisms are still a subject of dispute. We measured direction of laterality (preferential use of left or right paws) and degree of laterality (absolute difference between the use of left and right paws) in C57BL/6ByJ (B) and NZB/BlNJ (N) mice and in their F(1) and F(2) intercrosses. Measurements were taken of both forepaws and hind paws. Quantitative trait loci (QTL) did not emerge for direction but did for degree of laterality. One QTL for forepaw (LOD score = 5.6) and the second QTL for hind paw (LOD score = 7.2) were both located on chromosome 4 and their peaks were within the same confidence interval. A QTL for plasma luteinizing hormone concentration was also found in the confidence interval of these two QTL. These results suggest that the physiological mechanisms underlying degree of laterality react to gonadal steroids.

Stereotactic Ablative Radiation Therapy for the Treatment of Early-stage Non-Small-Cell Lung Cancer: CEPO Review and Recommendations.

BACKGROUND: Lung cancer is the second most diagnosed cancer and the leading cause of cancer-related mortality in Canada. Surgical resection is the treatment of choice for patients with stage I non-small-cell lung cancer (NSCLC). However, 20% to 30% of them are deemed medically inoperable and may be offered radiation therapy. Standard external-beam radiation therapy (EBRT) is associated with high rates of local recurrence and poor long-term survival. Stereotactic ablative radiation therapy (SABR) is increasingly being proposed for inoperable patients, and the use of this treatment modality for operable patients is also being contemplated. The objective of this guideline is to review the efficacy and safety of SABR in these two clinical situations and to develop evidence-based recommendations. METHOD: A review of the scientific literature published up to December 2013 was performed. A total of 44 publications were included. RECOMMENDATIONS: Considering the evidence available to date, the Comité de l'évolution des pratiques en oncologie recommends the following: (1) for medically operable patients with stage T1-2N0M0 NSCLC, surgery remains the standard treatment because comparative data regarding the efficacy of SABR and surgery are currently insufficient for SABR to be considered an equivalent alternative to surgery for these patients; (2) for medically inoperable patients with stage T1-2N0M0 NSCLC or medically operable patients who refuse surgery, SABR should be preferred to standard EBRT (grade B recommendation); (3) the biological equivalent dose (BED(10)) used for SABR treatment should be at least 100 Gy (grade B recommendation); (4) for patients with a central tumor, a large-volume tumor (large planning target volume) or severe pulmonary comorbidity, a risk-adaptive schedule should be used (dose reduction or increase in the number of fractions; grade B recommendation); (5) the choice of using SABR to treat NSCLC should be discussed within tumor boards; treatment with SABR (or with standard EBRT) should not be considered for patients whose life expectancy is very limited because of comorbidities (grade D recommendation).