Body Composition in Advanced Non-Small Cell Lung Cancer Treated With Immunotherapy.

Importance: The association between body composition (BC) and cancer outcomes is complex and incompletely understood. Previous research in non-small-cell lung cancer (NSCLC) has been limited to small, single-institution studies and yielded promising, albeit heterogeneous, results. Objectives: To evaluate the association of BC with oncologic outcomes in patients receiving immunotherapy for advanced or metastatic NSCLC. Design, Setting, and Participants: This comprehensive multicohort analysis included clinical data from cohorts receiving treatment at the Dana-Farber Brigham Cancer Center (DFBCC) who received immunotherapy given alone or in combination with chemotherapy and prospectively collected data from the phase 1/2 Study 1108 and the chemotherapy arm of the phase 3 MYSTIC trial. Baseline and follow-up computed tomography (CT) scans were collected and analyzed using deep neural networks for automatic L3 slice selection and body compartment segmentation (skeletal muscle [SM], subcutaneous adipose tissue [SAT], and visceral adipose tissue). Outcomes were compared based on baseline BC measures or their change at the first follow-up scan. The data were analyzed between July 2022 and April 2023. Main Outcomes and Measures: Hazard ratios (HRs) for the association of BC measurements with overall survival (OS) and progression-free survival (PFS). Results: A total of 1791 patients (878 women [49%]) with NSCLC were analyzed, of whom 487 (27.2%) received chemoimmunotherapy at DFBCC (DFBCC-CIO), 825 (46.1%) received ICI monotherapy at DFBCC (DFBCC-IO), 222 (12.4%) were treated with durvalumab monotherapy on Study 1108, and 257 (14.3%) were treated with chemotherapy on MYSTIC; median (IQR) ages were 65 (58-74), 66 (57-71), 65 (26-87), and 63 (30-84) years, respectively. A loss in SM mass, as indicated by a change in the L3 SM area, was associated with worse oncologic outcome across patient groups (HR, 0.59 [95% CI, 0.43-0.81] and 0.61 [95% CI, 0.47-0.79] for OS and PFS, respectively, in DFBCC-CIO; HR, 0.74 [95% CI, 0.60-0.91] for OS in DFBCC-IO; HR, 0.46 [95% CI, 0.33-0.64] and 0.47 [95% CI, 0.34-0.64] for OS and PFS, respectively, in Study 1108; HR, 0.76 [95% CI, 0.61-0.96] for PFS in the MYSTIC trial). This association was most prominent among male patients, with a nonsignificant association among female patients in the MYSTIC trial and DFBCC-CIO cohorts on Kaplan-Meier analysis. An increase of more than 5% in SAT density, as quantified by the average CT attenuation in Hounsfield units of the SAT compartment, was associated with poorer OS in 3 patient cohorts (HR, 0.61 [95% CI, 0.43-0.86] for DFBCC-CIO; HR, 0.62 [95% CI, 0.49-0.79] for DFBCC-IO; and HR, 0.56 [95% CI, 0.40-0.77] for Study 1108). The change in SAT density was also associated with PFS for DFBCC-CIO (HR, 0.73; 95% CI, 0.54-0.97). This was primarily observed in female patients on Kaplan-Meier analysis. Conclusions and Relevance: The results of this multicohort study suggest that loss in SM mass during systemic therapy for NSCLC is a marker of poor outcomes, especially in male patients. SAT density changes are also associated with prognosis, particularly in female patients. Automated CT-derived BC measurements should be considered in determining NSCLC prognosis.

Early knee OA definition-what do we know at this stage? An imaging perspective.

While criteria for early-stage knee osteoarthritis (OA) in a primary care setting have been proposed, the role of imaging has been limited to radiography using the standard Kellgren-Lawrence classification. Standardized imaging and interpretation are critical with radiographs, yet studies have also shown that even early stages of radiographic OA already demonstrate advanced damage to knee joint tissues such as cartilage, menisci, and bone marrow. Morphological magnetic resonance imaging (MRI) shows degenerative damage earlier than radiographs and definitions for OA using MRI have been published though no accepted definition of early OA based on MRI is currently available. The clinical significance of structural abnormalities has also not been well defined, and the differentiation between normal aging and structural OA development remains a challenge. Compositional MRI of cartilage provides information on biochemical, degenerative changes within the cartilage matrix before cartilage defects occur and when cartilage damage is potentially reversible. Studies have shown that cartilage composition can predict cartilage loss and radiographic OA. However, while this technology is most promising for characterizing early OA it has currently limited clinical application. Better standardization of compositional MRI is required, which is currently work in progress. Finally, there has been renewed interest in computed tomography (CT) for assessing early knee OA as new techniques such as weight bearing and spectral CT are available, which may provide information on joint loading, cartilage, and bone and potentially have a role in better characterizing early OA. In conclusion, while imaging may have a limited role in diagnosing early OA in a primary care setting, there are advanced imaging technologies available, which detect early degeneration and may thus significantly alter management as new therapeutic modalities evolve.

Bridging disciplines, knowledge systems and cultures in pest management.

The success of research in integrated environmental and natural resource management relies on the participation and involvement of different disciplines and stakeholders. This can be difficult to achieve in practice because many initiatives fail to address the underlying social processes required for successful engagement and social learning. We used an action research approach to support a research-based group with a range of disciplinary and stakeholder expertise to critically reflect on their engagement practice and identify lessons around how to collaborate more effectively. This approach is provided here as a guide that can be used to support reflective research practice for engagement in other integration-based initiatives. This paper is set in the context of an integrated wildlife management research case study in New Zealand. We illustrate how multi-, inter- and trans-disciplinary approaches can provide a framework for considering the different conversations that need to occur in an integrated research program. We then outline rubrics that list the criteria required in inter- and trans-disciplinary collaborations, along with examples of effective engagement processes that directly support integration through such efforts. Finally, we discuss the implications of these experiences for other researchers and managers seeking to improve engagement and collaboration in integrated science, management and policy initiatives. Our experiences reaffirm the need for those involved in integrative initiatives to attend to the processes of engagement in both formal and informal settings, to provide opportunities for critical reflective practice, and to look for measures of success that acknowledge the importance of effective social process.

Innovative developments for long-term mammalian pest control.

BACKGROUND: Invasive mammalian pests have inflicted substantial environmental and economic damage on a worldwide scale. RESULTS: Over the last 30 years there has been minimal innovation in the development of new control tools. The development of new vertebrate pesticides, for example, has been largely restricted due to the costly and time-consuming processes associated with testing and registration. CONCLUSION: In this article we discuss recent progress and trends in a number of areas of research aimed to achieve long-term population suppression or eradication of mammalian pest species. The examples discussed here are emerging from research being conducted in New Zealand, where invasive mammalian pests are one of the greatest threats facing the national environment and economy.