Stage III Non–Small-Cell Lung Cancer: Population-Based Patterns of Treatment in British Columbia, Canada

Introduction:Management of Stage III non–small-cell lung cancer (NSCLC) involves surgery, radiotherapy (RT), chemotherapy, and best supportive care. The aims were to describe the patterns of treatment in a population-based cohort of patients, and compare utilization of RT and chemotherapy to model estimates of need.Methods:Patients diagnosed with Stage III NSCLC between January 1, 2000, to December 31, 2007, were identified from the British Columbia Cancer Agency database. Patients who had prior or concomitant malignancy were excluded. Patient demographics, tumor characteristics, and initial treatment were extracted. Survival data were derived from the British Columbia Vital Statistics Death Listings.Results:2365 patients with Stage III NSCLC were referred, of which 212 patients were excluded, leaving 2153 patients in the study population. Median age was 69 years. Disease stage was IIIA in 49% and IIIB in 51%. Histologies were squamous-cell carcinoma (31%), adenocarcinoma (27%), NSCLC not otherwise specified (31%), and other pathology (11%). Initial treatment included surgery in 12%, RT in 78%, and chemotherapy in 31%. Predicted RT utilization was 77% to 87% and chemotherapy 78%. From 2000 to 2007, curative-intent treatment increased from 21% to 35%, chemoradiotherapy from 8% to 18.6%, and concurrent chemoradiotherapy from 5.1% to 17.6%. Median survival was 30 months for patients who had curative surgery, 21 months for curative RT, 8 months for palliative treatment, and 5 months for best supportive care (p < 0.001).Conclusion:RT utilization was similar to that predicted by models whereas chemotherapy utilization was less. During the study period, the proportion of patients receiving curative chemoradiotherapy doubled and of those receiving concurrent chemoradiotherapy trebled

Iskorištavanje hrane, metaboliti u krvi i ponašanje pri unosu hrane u teladi sahival pasmina odabrane s obzirom na visoki ili niski ostatni unos hrane

This study aimed to evaluate differences in feed utilization between low and high residual feed intake (RFI) in Sahiwal calves by comparing performance, ingestive behavior and blood metabolites. Eighteen, growing, female Sahiwal calves (aged 10-14 months; body weight (BW) 100-125 kg) were fed ad libitum on a total mixed ration for 90 d. RFI varied from -0.53 to 0.40 kg dry matter (DM)/d with a mean RFI of -0.27 to 0.17 kg DM/d in low and high RFI Sahiwal calves, respectively. Calves with low RFI consumed 26% less DM and required 35% less metabolizable energy for body maintenance (MEm) compared to high RFI, yet gained at a similar rate. Low RFI calves digest feed more efficiently than less efficient calves. Conventional efficiency measures also showed better efficiency in low RFI than high RFI calves. Low RFI calves spent less time in feeding, rumination, and chewing. Higher plasma concentrations of insulin-like growth factor-1 (IGF-1), growth hormone (GH), and creatinine, and lower concentrations of albumin, plasma urea nitrogen (PUN), and triglycerides were observed in the low RFI group than the high RFI group. However, plasma total protein, glucose, cholesterol, non esterified fatty acid (NEFA), beta-hydroxy butyric acid (BHBA), calcium (Ca), and phosphorus (P) concentrations were similar in both groups. In summary, low RFI calves utilized feed more efficiently by spending less time and energy in feeding, and the variability in blood metabolites might be due to differences in body metabolism.Ovo istraživanje imalo je za cilj, na temelju proizvodnje, ponašanja kod unosa hrane i metabolita u krvi, procijeniti razlike u iskorištavanju hrane između sahival teladi s niskim ostatnim unosom hrane i visokim ostatnim unosom hrane (Residual Feed Intake - RFI). Osamnaest sahival teladi ženskog spola (u dobi od 10 do -14 mjeseci i tjelesnoj masi od 100 do 125 kg) hranjeno je 90 dana, ad libitum, kompletnim mješovitim obrokom. Ostatni unos hrane kretao se od -0,53 do 0,40 kg suhe tvari/d, sa srednjom vrijednošću od -0,27 kod sahival teladi s niskim ostatnim unosom i srednjom vrijednošću od 0,17 kg kod sahival teladi visokim ostatnim unosom hrane. Iako je telad s niskim ostatnim unosom hrane u odnosu na onu s visokim ostatnim unosom hrane konzumirala 26% manje suhe tvari i zahtijevala 35 % manje uzdržne energije za metabolizam tijela, prirast obje skupne teladi kretao se po sličnoj stopi. Telad s niskim ostatnim unosom hrane imala je učinkovitiju hranidbu što su pokazali i standarni pokazatelji prema kojima je ta telad provela hranidbu u kraćem vremenu, uz kraće žvakanje i preživanje. U usporedbi s teladi koja ima viši ostatni unos hrane, telad s niskim ostatnim unosom hrane imala je u plazmi veće koncentracije inzulinu-sličnog faktora rasta-1 (IGF-1), hormona rasta (GH) i kreatinina, te niže koncentracije albumina, dušika iz ureje i triglicerida. Koncentracije ukupnih proteina, glukoze, kolesterola, neesterificirane masne kiseline (NEFA), betahidroksi maslačne kiseline (BHBA), kalcija (Ca) i fosfora (P) bile su slične u obje skupine teladi. Sažeto, telad s niskim ostatnim unosom hrane iskorištavala je hranu učinkovitije, provodeći kraće vrijeme i trošeći manje energije prilikom hranjenja, a varijacije metabolita u krvi mogle bi biti posljedica razlika u metabolizmu

Feasibility of free breathing Lung MRI for Radiotherapy using non-Cartesian k-space acquisition schemes

Objective: To test a free-breathing MRI protocol for anatomical and functional assessment during lung cancer radiotherapy by assessing two non-Cartesian acquisition schemes based on T1 weighted 3D gradient recall echo sequence: (i) stack-of stars (StarVIBE) and (ii) spiral (SpiralVIBE) trajectories. Methods: MR images on five healthy volunteers were acquired on a wide bore 3T scanner (MAGNETOM Skyra, Siemens Healthcare, Erlangen, Germany). Anatomical image quality was assessed on: (1) free breathing (StarVIBE), (2) the standard clinical sequence (volumetric interpolated breath-hold examination, VIBE) acquired in a 20 second (s) compliant breath-hold and (3) 20 s non-compliant breath-hold. For functional assessment, StarVIBE and the current standard breath-hold time-resolved angiography with stochastic trajectories (TWIST) sequence were run as multiphase acquisitions to replicate dynamic contrast enhancement (DCE) in one healthy volunteer. The potential application of the SpiralVIBE sequence for lung parenchymal imaging was assessed on one healthy volunteer. Ten patients with lung cancer were subsequently imaged with the StarVIBE and SpiralVIBE sequences for anatomical and structural assessment. For functional assessment, free-breathing StarVIBE DCE protocol was compared with breath-hold TWIST sequences on four prior lung cancer patients with similar tumour locations. Image quality was evaluated independently and blinded to sequence information by an experienced thoracic radiologist. Results: For anatomical assessment, the compliant breath-hold VIBE sequence was better than free-breathing StarVIBE. However, in the presence of a non-compliant breath-hold, StarVIBE was superior. For functional assessment, StarVIBE outperformed the standard sequence and was shown to provide robust DCE data in the presence of motion. The ultrashort echo of the SpiralVIBE sequence enabled visualisation of lung parenchyma. Conclusion: The two non-Cartesian acquisition sequences, StarVIBE and SpiralVIBE, provide a free-breathing imaging protocol of the lung with sufficient image quality to permit anatomical, structural and functional assessment during radiotherapy. Advances in knowledge: Novel application of non-Cartesian MRI sequences for lung cancer imaging for radiotherapy. Illustration of SpiralVIBE UTE sequence as a promising sequence for lung structural imaging during lung radiotherapy

A review of segmentation and deformable registration methods applied to adaptive cervical cancer radiation therapy treatment planning

Objective: Manual contouring and registration for radiotherapy treatment planning and online adaptation for cervical cancer radiation therapy in computed tomography (CT) and magnetic resonance images (MRI) are often necessary. However manual intervention is time consuming and may suffer from inter or intra-rater variability. In recent years a number of computer-guided automatic or semi-automatic segmentation and registration methods have been proposed. Segmentation and registration in CT and MRI for this purpose is a challenging task due to soft tissue deformation, inter-patient shape and appearance variation and anatomical changes over the course of treatment. The objective of this work is to provide a state-of-the-art review of computer-aided methods developed for adaptive treatment planning and radiation therapy planning for cervical cancer radiation therapy. Methods: Segmentation and registration methods published with the goal of cervical cancer treatment planning and adaptation have been identified from the literature (PubMed and Google Scholar). A comprehensive description of each method is provided. Similarities and differences of these methods are highlighted and the strengths and weaknesses of these methods are discussed. A discussion about choice of an appropriate method for a given modality is provided. Results: In the reviewed papers a Dice similarity coefficient of around 0.85 along with mean absolute surface distance of 2-4. mm for the clinically treated volume were reported for transfer of contours from planning day to the treatment day. Conclusions: Most segmentation and non-rigid registration methods have been primarily designed for adaptive re-planning for the transfer of contours from planning day to the treatment day. The use of shape priors significantly improved segmentation and registration accuracy compared to other models

Psychological distress and quality of life in lung cancer: The role of health-related stigma, illness appraisals and social constraints

Psycho-Oncology Published by John Wiley &amp; Sons Ltd. Objective Health-related stigma is associated with negative psychological and quality of life outcomes in lung cancer patients. This study describes the impact of stigma on lung cancer patients' psychological distress and quality of life and explores the role of social constraints and illness appraisal as mediators of effect. Methods A self-administered cross-sectional survey examined psychological distress and quality of life in 151 people (59% response rate) diagnosed with lung cancer from Queensland and New South Wales. Health-related stigma, social constraints and illness appraisals were assessed as predictors of adjustment outcomes. Results Forty-nine percent of patients reported elevated anxiety; 41% were depressed; and 51% had high global distress. Health-related stigma was significantly related to global psychological distress and quality of life with greater stigma and shame related to poorer outcomes. These effects were mediated by illness appraisals and social constraints. Conclusions Health-related stigma appears to contribute to poorer adjustment by constraining interpersonal discussions about cancer and heightening feelings of threat. There is a need for the development and evaluation of interventions to ameliorate the negative effects of health-related stigma among lung cancer patients

Impaired regeneration in LGMD2A supported by increased Pax7 positive satellite cell content and muscle specific microRNA dysregulation

Introduction—Recent in vitro studies suggest that CAPN3 deficiency leads initially to accelerated myofiber formation followed by depletion of satellite cells (SC). In normal muscle, upregulation of miR-1 and miR-206 facilitates transition from proliferating SCs to differentiating myogenic progenitors. Methods—We examined the histopathological stages, Pax7 SC content, and muscle specific microRNA expression in biopsy specimens from well-characterized LGMD 2A patients to gain insight into disease pathogenesis. Results—Three distinct stages of pathological changes were identified that represented the continuum of the dystrophic process from prominent inflammation with necrosis and regeneration to prominent fibrosis, which correlated with age and disease duration. Pax7-positive SCs were highest in fibrotic group and correlated with down-regulation of miR-1, miR-133a, and miR-206. Conclusions—These observations, and other published reports, are consistent with microRNA dysregulation leading to inability of Pax7-positive SCs to transit from proliferation to differentiation. This results in impaired regeneration and fibrosis.This work was supported by NIH NIAMS U54 AR050733-05, Jesse’s Journey, and the muscular Dystrophy Associatio

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

Decision making in lung cancer : how applicable are the guidelines?

Modelling demand for radiotherapy is contingent on the uniform application of clinical practice guidelines. However, decision making in lung cancer is a complex process requiring the integration of multimodality treatment in patients who frequently have underlying comorbidities. Population studies have shown that guideline adherence in lung cancer is modest, ranging from 44 to 52%. The application of guideline treatment decreases with increasing age and the presence of comorbidities. Patient and clinician attitudes also impact on this. In some regions, sociodemographic factors, such as lower income and non-White race, have been associated with a lack of guideline treatment. One of the major barriers in treating lung cancer patients according to guidelines is the mismatch between the clinic population and those enrolled in clinical trials from which evidence is derived. The lung cancer clinic population often consists of patients who are older, have multiple comorbidities and are of borderline performance status, all characteristics that are usually exclusion criteria for clinical trials. Hence, there is uncertainty not only about the magnitude of benefit, but also potential toxicities of guideline treatment. Further research is necessary in order to define the best treatment in these patients and thus increase the applicability of guidelines to the general lung cancer population. Lung cancer is an extreme example of the difficulties in translating evidence into clinical practice. The applicability of guidelines to specific cancer populations will affect the modelling of demand for radiotherapy and other treatment modalities

Radiotherapy in lung cancer

Radiotherapy is an important modality in the treatment of lung cancer. In Australia, up to 76% of patients have an indication for radiotherapy at diagnosis. This includes curative radiotherapy for patients with inoperable stage I and II non-small cell lung cancer, and in combination with chemotherapy, for patients with stage III non-small cell lung cancer and limited stage small cell lung cancer. There are challenges in delivering curative radiotherapy to this group of patients, many of whom have smoking-related comorbidities. However, newer technologies allow selection of appropriate patients for treatment, improve identification of the tumour, individualise radiotherapy treatment according to patient specific motion and reduce normal tissue toxicities. Image guided radiotherapy is increasingly becoming the standard of care, whereby the tumour position is confirmed on cone-beam CT performed on the linear accelerator prior to treatment. Intensity modulated radiotherapy is improving dose conformality and avoidance of normal tissue structures. Stereotactic ablative radiotherapy is currently being evaluated as a treatment option for patients with inoperable stage I non-small cell lung cancer. Radiotherapy is also an important palliative treatment for lung cancer, with well-established indications for palliation of thoracic symptoms such as airway obstruction, chest pain, cough and haemoptysis. Bone and brain metastases are common in lung cancer and radiotherapy remains the prime modality for alleviating symptoms from these. Multidisciplinary discussion of lung cancer patients is essential to ensure that appropriate patients receive the evidence-based benefits of radiotherapy