Background

Clinical workup and treatment guidelines have been published by the National Comprehensive Cancer Network (NCCN) to ensure patients are treated uniformly and appropriately. This study sought to retrospectively review patients with a new diagnosis of sarcoma who were treated in a National Cancer Institute (NCI) designated center and determine compliance rates with guidelines for sarcoma.

Aim

To evaluate our compliance of NCCN sarcoma guidelines at a major NCI designated center and to report instances of deviation that could be used for future studies to improve patient care.

Methods

Data was collected retrospectively as an internal review and quality assessment of 35 newly diagnosed and treated patients. Demographic data were recorded and information concerning whether patients had appropriate imaging, biopsy and management. Variables of interest were expressed as raw numbers and percentages.

Results

Primary site imaging was obtained in 100% of cases. Chest and full-body imaging were obtained in 97% and 100% of indicated cases, respectively. Tissue was obtained preoperatively in 97% of cases. Imaging was reviewed at multidisciplinary Treatment Planning Conference (TPC) in 97% of cases. Pathology was reviewed in 94% of cases in TPC. Both tumor, node, metastasis staging and plan of care were reviewed in 100% of cases in TPC. Treatment guidelines were followed in 94% of cases reviewed.

Conclusion

This study evaluated the workup and treatment provided by a single NCI designated sarcoma service to a series of patients with pathologies defined with the NCCN sarcoma treatment guidelines. Although adherence to NCCN was reported to be very high future prospective studies are required to investigate whether NCCN guidelines impact patient outcomes.

Natural populations persist in complex environments, where biotic stressors, such as pathogen and insect communities, fluctuate temporally and spatially. These shifting biotic pressures generate heterogeneous selective forces that can maintain standing natural variation within a species. To directly test if genes containing causal variation for the Arabidopsis thaliana defensive compounds, glucosinolates (GSL) control field fitness and are therefore subject to natural selection, we conducted a multi-year field trial using lines that vary in only specific causal genes. Interestingly, we found that variation in these naturally polymorphic GSL genes affected fitness in each of our environments but the pattern fluctuated such that highly fit genotypes in one trial displayed lower fitness in another and that no GSL genotype or genotypes consistently out-performed the others. This was true both across locations and within the same location across years. These results indicate that environmental heterogeneity may contribute to the maintenance of GSL variation observed within Arabidopsis thaliana.

Despite the growing number of studies showing that genotype × environment and epistatic interactions control fitness, the influences of epistasis × environment interactions on adaptive trait evolution remain largely uncharacterized. Across three field trials, we quantified aliphatic glucosinolate (GSL) defense chemistry, leaf damage, and relative fitness using mutant lines of Arabidopsis thaliana varying at pairs of causal aliphatic GSL defense genes to test the impact of epistatic and epistasis × environment interactions on adaptive trait variation. We found that aliphatic GSL accumulation was primarily influenced by additive and epistatic genetic variation, leaf damage was primarily influenced by environmental variation and relative fitness was primarily influenced by epistasis and epistasis × environment interactions. Epistasis × environment interactions accounted for up to 48% of the relative fitness variation in the field. At a single field site, the impact of epistasis on relative fitness varied significantly over 2 yr, showing that epistasis × environment interactions within a location can be temporally dynamic. These results suggest that the environmental dependency of epistasis can profoundly influence the response to selection, shaping the adaptive trajectories of natural populations in complex ways, and deserves further consideration in future evolutionary studies.