Use of guideline-recommended adjuvant therapies and survival outcomes for people with colorectal cancer at tertiary referral hospitals in South Australia

Rationale, aims and objectives: Adjuvant care for colorectal cancer (CRC) has increased over the past 3 decades in South Australia (SA) in accordance with national treatment guidelines. This study explores the (1) receipt of adjuvant therapy for CRC in SA as related to national guideline recommendations, with a focus on stage C colon and stage B and C rectal cancer; (2) timing of these adjuvant therapies in relation to surgery; and (3) comparative survival outcomes. Methods: Data from the SA Clinical Cancer Registry from 4 tertiary referral hospitals for 2000 to 2010 were examined. Patterns of care were compared with treatment guidelines using multivariable logistic regression. Disease‐specific survivals were calculated by treatment pathway. Results: Four hundred forty‐three (60%) patients with stage C colon cancer and 363 (46%) with stage B and C rectal cancer received guideline‐recommended care. While an overall increase in proportion receiving adjuvant care was not evident across the study period, the proportion having neoadjuvant care increased substantially. Older age was an independent predictor of not receiving adjuvant care. Patients with stage C colon cancer who received recommended adjuvant care had a higher 5‐year survival than those not receiving this care, ie, 71.2% vs 53.2%. Similarly adjuvant therapy was associated with better outcomes for stage C rectal cancers. The median time for receiving adjuvant care was 8 weeks. Conclusions: Survival was better for stage C CRC treated according to guidelines. Adjuvant care should be provided except where clear contraindications present. Other possible contributors to guideline adherence warranting additional investigation include co‐morbidity status, multidisciplinary team involvement, and choice.Pamela Adelson, Kellie Fusco, Christos Karapetis, David Wattchow, Rohit Joshi, Timothy Price, Greg Sharplin, David Rode

Healthy Living after Cancer: A dissemination and implementation study evaluating a telephone-delivered healthy lifestyle program for cancer survivors

© 2015 Eakin et al. Background: Given evidence shows physical activity, a healthful diet and weight management can improve cancer outcomes and reduce chronic disease risk, the major cancer organisations and health authorities have endorsed related guidelines for cancer survivors. Despite these, and a growing evidence base on effective lifestyle interventions, there is limited uptake into survivorship care. Methods/Design: Healthy Living after Cancer (HLaC) is a national dissemination and implementation study that will evaluate the integration of an evidence-based lifestyle intervention for cancer survivors into an existing telephone cancer information and support service delivered by Australian state-based Cancer Councils. Eligible participants (adults having completed cancer treatment with curative intent) will receive 12 health coaching calls over 6 months from Cancer Council nurses/allied health professionals targeting national guidelines for physical activity, healthy eating and weight control. Using the RE-AIM evaluation framework, primary outcomes are service-level indicators of program reach, adoption, implementation/costs and maintenance, with secondary (effectiveness) outcomes of patient-reported anthropometric, behavioural and psychosocial variables collected at pre- and post-program completion. The total participant accrual target across four participating Cancer Councils is 900 over 3 years. Discussion: The national scope of the project and broad inclusion of cancer survivors, alongside evaluation of service-level indicators, associated costs and patient-reported outcomes, will provide the necessary practice-based evidence needed to inform future allocation of resources to support healthy living among cancer survivors. Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12615000882527(registered on 24/08/2015

CAR T in patients with large B-cell lymphoma not fit for autologous transplant

Large B-cell lymphoma (LBCL) patients with comorbidities and/or advanced age are increasingly considered for treatment with CD19 CAR T, but data on the clinical benefit of CAR T in the less fit patient population are still limited. We analysed outcomes of consecutive patients approved for treatment with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) by the UK National CAR T Clinical Panel, according to fitness for autologous stem cell transplant (ASCT). 81/404 (20%) of approved patients were deemed unfit for ASCT. Unfit patients were more likely to receive tisa-cel versus axi-cel (52% vs. 48%) compared to 20% versus 80% in ASCT-fit patients; p < 0.0001. The drop-out rate from approval to infusion was significantly higher in the ASCT-unfit group (34.6% vs. 23.5%; p = 0.042). Among infused patients, response rate, progression-free and overall survival were similar in both cohorts. CAR T was well-tolerated in ASCT-unfit patients with an incidence of grade ≥3 cytokine release syndrome and neurotoxicity of 2% and 11%, respectively. Results from this multicentre real-world cohort demonstrate that CD19 CAR T can be safely delivered in carefully selected older patients and patients with comorbidities who are not deemed suitable for transplant

Early administration of IL-6RA does not prevent radiation-induced lung injury in mice

<p>Abstract</p> <p>Background</p> <p>Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6) is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA) could ameliorate radiation-induced lung injury in mice.</p> <p>Methods</p> <p>BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1) or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA). Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline.</p> <p>Results</p> <p>The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control.</p> <p>Conclusions</p> <p>Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.</p

Effekte von Morphin, Fentanyl und Ketamin auf leukozytäre Funktion, Transkriptionsfaktoren und Interleukin-8-Synthese

In der hier vorliegenden Arbeit wird der Einfluß der in der Anästhesie gebräuchlichen Analgetika Morphin, Fentanyl und Ketamin auf die Funktion neutrophiler Granulozyten dargelegt. Dazu wurden immunologische, durchflußzytometrische und molekularbiologische Untersuchungsverfahren eingesetzt. Die untersuchten Substanzen modulieren die Funktion, transkriptionelle Regulation und Proteinexpression von Granulozyten in unterschiedlicher Weise. Morphin hemmt die Funktion neutrophiler Granulozyten konzentrations- und zeitabhängig. Erstmals wird dargestellt, daß der inhibitorische Effekt von Morphin auf die Phagozytose und den Oxidativen Burst durch die Freisetzung von NO als second messenger hervorgerufen wird. Die verminderte Expression von Komplement-, Fcg- und CD14-Rezeptoren korreliert mit diesen Funktionseinschränkungen. Zudem reguliert Morphin die intrazelluläre Signaltransduktion und führt dadurch zu einer Minderung der LPS-induzierten DNA-Bindungsaktivität der Transkriptionsfaktoren NF-kB und AP-1. Die hemmende Wirkung von Morphin auf transkriptionsregulierende Proteine wird in dieser Arbeit erstmals an humanen Leukozyten nachgewiesen. Dabei stellt die Morphin-abhängige Freisetzung von NO das Schlüsselereignis für die hemmenden Effekte von Morphin dar: Durch NOS-Antagonisten kann die Morphin-induzierte Hemmung von Rezeptorenexpression, Granulozytenfunktion und Transkriptionsfaktoren verhindert werden, während NO-Donoren die Morphin-Wirkung imitieren. Die Blockade von Opiatrezeptoren mit Naloxon hebt die inhibierende Wirkung von Morphin ebenfalls auf, so daß eine Bindung an NO-freisetzende µ-Rezeptoren auf Granulozyten als kausaler Mechanismus angesehen werden kann. Die Inhibierung der Transkriptionsfaktoren NF-kB und AP-1 korreliert im Vollblut nicht mit einer verminderten Produktion von IL-8 als NF-kB- bzw. AP-1-abhängigem Mediator. Die exakten intrazellulären Mechanismen und die funktionelle Bedeutung dieser Granulozyten-inhibierenden Effekte von Morphin auf das Entzündungsgeschehen müssen in zukünftigen Untersuchungen geklärt werden. Fentanyl zeigt weder aktivierende noch inhibierende Wirkungen auf Granulozytenfunktion und Expression von Oberflächenrezeptoren. Grundlage hierfür kann die mangelnde Affinität von Fentanyl für die auf Leukozyten exprimierten Opiatrezeptoren sein. Basierend auf der Annahme, daß diese Substanz immunologisch inert ist, wurden Effekte auf transkriptionelle Regulation und Proteinsynthese nicht untersucht. Ketamin hemmt die Granulozytenfunktion und die Expression von Komplement-, Fcg- und CD14-Rezeptoren konzentrationsabhängig, wobei die Dauer der Ketamin-Inkubation nicht von Bedeutung ist. Erstmals wird in dieser Arbeit ein inhibitorischer Effekt von Ketamin auf die LPS-induzierte DNA-Bindungsaktivität der Transkriptionsfaktoren NF-kB und AP-1 beschrieben, wobei konsekutiv die leukozytäre Produktion von IL-8 auf transkriptioneller Ebene gehemmt wird. Das Ausmaß der Hemmung durch Ketamin hängt dabei von der zur Stimulation eingesetzten LPS-Dosierung ab. Im Gegensatz zu Morphin-induzierten Veränderungen sind diese Effekte unabhängig von NO als second messenger und werden nicht durch Opiat- oder NMDA-Rezeptoren vermittelt. Damit unterscheiden sich die Signaltransduktionswege Ketamin-vermittelter Effekte auf Immunzellen grundlegend von denjenigen, die für die anästhetische und psychomimetische Wirkung dieser Substanz im ZNS verantwortlich sind. Enantiomer-spezifische Effekte spielen für die immunsupprimierende Wirkung von Ketamin nur eine untergeordnete Rolle. Folgestudien sind erforderlich, um die an der Ketamin-abhängigen Inhibierung beteiligten intrazellulären Mediatoren und Stoffwechselwege in Leukozyten zu definieren. Der in dieser Studie erstmals zur Untersuchung von Analgetika-induzierten Veränderungen von Transkriptionsfaktoren angewandte durchflußzytometrische Vollblut-Assay weist eine hohe Reproduzierbarkeit auf, ermöglicht eine verläßliche und schnelle Quantifizierung des nukleären NF-kB- bzw. AP-1-Gehalts und liefert mit klassischen Verfahren vergleichbare Ergebnisse. Bei dieser Technik kann auf eine Zellseparation verzichtet werden, so daß die physiologischen Zustände im Vollblut berücksichtigt werden. Eine eventuelle Anwendung dieses Verfahrens zum Screening von Risikopatienten in Anästhesie und Intensivmedizin sollte in zukünftigen Untersuchungen evaluiert werden. Der differente Einfluß dieser Analgetika auf das Immunsystem sollte bei den verschiedenen Indikationen in Anästhesie, Intensivmedizin und Schmerztherapie Beachtung finden und in klinischen Studien weiter abgeklärt werden, um nicht nur eine effiziente Analgesie zu erzielen, sondern auch um etwaige Vor- bzw. Nachteile einer Immunmodulation durch diese Substanzen berücksichtigen zu können

The relationship between sun protection policies and practices in schools with primary-age students: the role of school demographics, policy comprehensiveness and SunSmart membership

First published online: November 22, 2013Schools can implement evidence-based sun protection policies that guide practices to help protect children from harmful sun exposure. This national study assessed the relationship between the existence and comprehensiveness of written policies and the comprehensiveness of sun protection practices. The impact of school demographics on the strength of the relationship was also examined, as was the possibility that 'SunSmart' membership would have an additional impact on practices, beyond having any formal policy. In 2011-12, staff members of 1573 schools catering to primary-age students completed a self-administered survey about sun protection policies and practices (response rate of 57%). Results showed that schools with a written policy had more comprehensive practices than schools without a written policy. The relationship between having a written policy and sun protection practices was stronger for remote schools compared with metropolitan and regional schools, and for schools catering to both primary and secondary students compared with primary students only. In addition, policy comprehensiveness was associated with practice comprehensiveness, and SunSmart membership was indirectly related to practice comprehensiveness via policy comprehensiveness. These results indicate that written policies relate to practice comprehensiveness, but the strength of the association can vary according to the characteristics of the organization.J. Dono, K. A. Ettridge, G. R. Sharplin and C. J. Wilso