Biospyder (United States)

Adding gene expression profiles (GEPs) to the current diagnostic work-up of aggressive large B-cell lymphomas may lead to the reclassification of patients, treatment changes and improved outcomes. A GEP test is in development using TempO-Seq® technology to distinguish Burkitt lymphoma (BL) and primary mediastinal large B-cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL), and to classify patients with DLBLC and to predict the benefit of (e.g.) adding bortezomib to R-CHOP therapy (RB-CHOP). This study aims to estimate the potential impact of a GEP test on costs and health outcomes to inform pricing and evidence generation strategies. Three decision models were developed comparing diagnostic strategies with and without GEP signatures over a lifetime horizon using a UK health and social care perspective. Inputs were taken from a recent clinical trial, literature and expert opinion. We estimated the maximum price of the test using a threshold of Great Britain Pound (GBP) 30,000 per quality-adjusted life-year (QALY). Sensitivity analyses were conducted. The estimated maximum threshold price for a combined test to be cost effective is GBP 15,352. At base-case values, the BL signature delivers QALY gains of 0.054 at an additional cost of GBP 275. This results in a net monetary benefit at a threshold of GBP 30,000 per QALY of GBP 1345. For PMBCL, the QALY gain was 0.0011 at a cost saving of GBP 406 and the net monetary benefit was GBP 437. The hazard ratio for the impact of treating BL less intensively must be at least 1.2 for a positive net monetary benefit. For identifying patients with the DLBCL subtype responsive to bortezomib, QALY gain was 0.2465 at a cost saving of GBP 6175, resulting in a net monetary benefit of GBP 13,570. In a probabilistic sensitivity analysis using 1000 simulations, a testing strategy was superior to a treat all with R-CHOP strategy in 81% of the simulations and with a cost saving in 92% assuming a cost price of zero. Our estimates show that the combined test has a high probability of being cost effective. There is good quality evidence for the benefit of subtyping DLBCL but the evidence on the number of patients reclassified to or from BL and PMBCL and the impact of a more precise diagnosis and the cost of treatment is weak. The developers can use the price estimate to inform a return on investment calculations. Evidence will be required of how well the TempO-Seq® technology performs compared to the testing GEP technology used for subtyping in the recent clinical trial. For BL and PMBCL elements of the test, evidence would be required of the number of patients reclassified and improved costing information would be useful. The diagnostic and therapeutic environment in haematological malignancies is fast moving, which increases the risk for developers of diagnostic tests.

Abstract Background: Racial/ethnic minority groups, including Hispanic Americans (HAs) and Native Americans (NAs), have a heavier burden of kidney cancer with a higher incidence and mortality than European Americans (EAs). However, HAs and NAs are under-represented in clinical and molecular genomic studies of renal cell carcinoma (RCC), the most common type of kidney cancer, and clinical and molecular characteristics of RCC among them are also unknown. We investigated variations in clinical and molecular characteristics of RCC patients. Methods: A total of 284 patients, including 90 HAs (31.6%) and 22 NAs (7.7%), who were diagnosed with RCC and without prior diagnosis of cancer were included to understand the patients' clinical characteristics. A subset of 51 samples were selected to screen for somatic mutations on the VHL gene, and 33 samples were selected for whole-transcriptome sequencing analysis. Results: Compared to EAs, HA and NA patients were diagnosed with RCC at younger ages (P<0.001). HA had about 5 years younger average age at diagnosis than EAs (55.2 vs. 60.6) and an over 2-fold increased odds of diagnosis before age 60 years (OR 2.50, 95% C.I.: 1.36-4.60). Mean age of diagnosis among NAs was 48.9, and NAs had more than 4-fold higher odds of diagnosis at a younger age (OR 4.12, 95% C.I.: 1.31-12.95). NA patients had higher body mass index than EA patients with 77.3% of NA obese patients. Diabetes was more common in HA (45.6%) and NA (50.0%) patients compared to EA (19.6%) patients. An RCC histologic subtype, clear cell RCC (ccRCC), was more common in HAs and NAs than EAs. Over 90% of HA patients had ccRCC, while only 77.6% of EA patients had ccRCC. HAs had increased odds of diagnosis with ccRCC compared to EAs (OR 2.39, 95% C.I.: 1.01-5.67). Among HAs, older patients were more likely to have advanced-stage RCC diagnosis (OR 7.06, 95% C.I.: 1.46-34.11). HAs who used Spanish as their primary language were more likely to have radical nephrectomy rather than partial nephrectomy (OR 5.13, 95% C.I.: 1.23-21.33). We detected pathogenic somatic mutations on the VHL gene, which is known to cause von Hippel-Lindau syndrome, in 4 patients, and these patients were younger than the patients without these mutations (45.5 vs. 57.1). We were able to assign 32 out of 33 patients into molecular subtypes (ccA and ccB). Molecular subtype could not be assigned to one HA patient with high-grade and advanced-stage ccRCC. Molecular subtype, ccA, was more common in HAs than EAs (64.3% vs. 41.2%), but this difference was not statistically significant. One gene, HABP2, showed evidence of differential expression between HA and EA tumors (PADJ<0.05) and was downregulated in HA tumors with log2 fold change <-2.0. Conclusion: HA and NA RCC patients had different clinical and molecular characteristics from EA patients. Impact: As we move toward a precision medicine approach for RCC care, it is necessary to better understand the clinical and molecular characteristics of these underserved HA and NA populations with high kidney cancer burden. Citation Format: Ken Batai, Alfredo Harb de la Rosa, Francine Gachupin, Elliot Imlaer, Erika R. Bracamonte, Bruce Seligmann, Benjamin R. Lee. Clinical and molecular profile of renal cell carcinoma in Hispanic Americans, Native Americans, and European Americans [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C059.

There is a gap between single-species model predictions, and empirical studies, regarding the effect of habitat fragmentation per se, i.e., a process involving the breaking apart of habitat without loss of habitat. Empirical works indicate that fragmentation can have positive as well as negative effects, whereas, traditionally, single-species models predict a negative effect of fragmentation. Within the class of reaction-diffusion models, studies almost unanimously predict such a detrimental effect. In this paper, considering a single-species reaction-diffusion model with a removal -- or similarly harvesting -- term, in two dimensions, we find both positive and negative effects of fragmentation of the reserves, i.e. the protected regions where no removal occurs. Fragmented reserves lead to higher population sizes for time-constant removal terms. On the other hand, when the removal term is proportional to the population density, higher population sizes are obtained on aggregated reserves, but maximum yields are attained on fragmented configurations, and for intermediate harvesting intensities.