scholarly journals Resource-efficient pooled sequencing expands translational impact in solid tumors

2021 ◽  
Vol 19 (2) ◽  
Author(s):  
Renzo DiNatale ◽  
◽  
Roy Mano ◽  
Vladimir Makarov ◽  
Nicole Rusk ◽  
...  

Intratumoral genetic heterogeneity (ITH) poses a significant challenge to utilizing sequencing for decision making in the management of cancer. Although sequencing of multiple tumor regions can address the pitfalls of ITH, it does so at a significant increase in cost and resource utilization. We propose a pooled multiregional sequencing strategy, whereby DNA aliquots from multiple tumor regions are mixed prior to sequencing, as a cost-effective strategy to boost translational value by addressing ITH while preserving valuable residual tissue for secondary analysis. Focusing on kidney cancer, we demonstrate that DNA pooling from as few as two regions significantly increases mutation detection while reducing clonality misattribution. This leads to an increased fraction of patients identified with therapeutically actionable mutations, improved patient risk stratification, and improved inference of evolutionary trajectories with an accuracy comparable to bona fide multiregional sequencing. The same approach applied to non-small-cell lung cancer data substantially improves tumor mutational burden (TMB) detection. Our findings demonstrate that pooled DNA sequencing strategies are a cost-effective alternative to address intrinsic genetic heterogeneity in clinical settings.

2021 ◽  
Author(s):  
Renzo G DiNatale ◽  
Roy Mano ◽  
Vladimir Makarov ◽  
Nicole Rusk ◽  
Esther Drill ◽  
...  

Intratumoral genetic heterogeneity (ITH) poses a significant challenge to utilizing sequencing for decision making in the management of cancer. Although sequencing of multiple tumor regions can address the pitfalls of ITH, it does so at a significant increase in cost and resource utilization. We propose a pooled multiregional sequencing strategy, whereby DNA aliquots from multiple tumor regions are mixed prior to sequencing, as a cost-effective strategy to boost translational value by addressing ITH while preserving valuable residual tissue for secondary analysis. Focusing on kidney cancer, we demonstrate that DNA pooling from as few as two regions significantly increases mutation detection while reducing clonality misattribution. This leads to an increased fraction of patients identified with therapeutically actionable mutations, improved patient risk stratification, and improved inference of evolutionary trajectories with an accuracy comparable to bona fide multiregional sequencing. The same approach applied to non-small-cell lung cancer data substantially improves tumor mutational burden (TMB) detection. Our findings demonstrate that pooled DNA sequencing strategies are a cost-effective alternative to address intrinsic genetic heterogeneity in clinical settings.


2021 ◽  
pp. 019394592110319
Author(s):  
Wonshik Chee ◽  
Eun-Ok Im

The purpose of the study was to explore the associations of sub-ethnicity to the survivorship experience of Asian American breast cancer survivors and identify the multiple factors that influenced their survivorship experience. This was a secondary analysis of the data among 94 Asian American breast cancer survivors from a larger ongoing study. Instruments included: questions on background characteristics, the perceived isolation scale, the Personal Resource Questionnaire, the Memorial Symptom Assessment Scale-Short Form, and the Functional Assessment of Cancer Therapy-Breast Cancer. Data were analyzed using hierarchical logistic and multiple regression analyses. After controlling for other factors, being a Japanese American (ref. = being a Chinese American) was significantly associated with pain scores (odds ratio [OR] = −0.32, p < .01), symptom distress scores ( β = −0.27, p < .01), and the quality of life scores ( β = 0.22, p = .03). Sub-ethnic variations in cultural attitudes, values, and beliefs need to be considered in future research/practice with Asian American breast cancer survivors.


2021 ◽  
pp. 096452842110557
Author(s):  
Trygve Skonnord ◽  
Arne Fetveit ◽  
Holgeir Skjeie ◽  
Mette Brekke ◽  
Margreth Grotle ◽  
...  

Objective: To assess the cost-effectiveness of a single treatment session of acupuncture, when applied in addition to usual care for acute low back pain (ALBP). Methods: Secondary analysis of a multicentre randomised controlled trial in Norwegian general practice. In total, 171 participants with ALBP ⩽14 days were randomised to a control group (CG) receiving usual care or to an acupuncture group (AG) receiving one additional session of Western medical acupuncture alongside usual care. Primary outcome measures for this cost-effectiveness analysis were quality-adjusted life years (QALYs), health care costs and societal costs at days 28 and 365, the incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB). The NMB was calculated on the basis of the Norwegian cost-effectiveness threshold of NOK 275,000 (USD 35,628) per QALY gained. Missing data were replaced by multiple chained imputation. Results: Eighty-six participants in the CG and 81 in the AG were included in the analysis. We found no QALY gain at day 28. At day 365, the incremental QALY of 0.035 was statistically significant. The differences in health care costs and societal costs were not statistically significant. Three out of four calculations led to negative ICERs (cost saving) and positive NMBs. For the health care perspective at day 365, the ICER was USD –568 per QALY and the NMB was USD 1265, with 95.9% probability of acupuncture being cost-effective. Conclusion: To our knowledge, this is the first cost-effectiveness analysis of acupuncture for ALBP. The findings indicate that acupuncture may be cost-effective from a 1-year perspective, but more studies are needed. Trial registration number: NCT01439412 (ClinicalTrials.gov).


2010 ◽  
Vol 4 (4) ◽  
pp. 339-343 ◽  
Author(s):  
Wendi Cross ◽  
Catherine Cerulli ◽  
Heidi Richards ◽  
Hua He ◽  
Jack Herrmann

ABSTRACTObjective: Disaster mental health (DMH) is vital to comprehensive disaster preparedness for communities. A train-the-trainer (TTT) model is frequently used in public health to disseminate knowledge and skills to communities, although few studies have examined its success. We report on the development and implementation of a DMH TTT program and examine variables that predict dissemination.Methods: This secondary analysis examines 140 community-based mental health providers' participation in a TTT DMH program in 2005–2006. Instructors' dissemination of the training was followed for 12 months. Bivariate and multivariate analyses were conducted to predict dissemination of the training program.Results: Sixty percent of the trainees in the DMH TTT program conducted training programs in the 12-month period following being trained. The likelihood of conducting training programs was predicted by a self-report measure of perceptions of transfer of training. The number of individuals subsequently trained (559) was predicted by prior DMH training and sex. No other variables predicted dissemination of DMH training.Conclusions: The TTT model was moderately successful in disseminating DMH training. Intervention at the organizational and individual level, as well as training modifications, may increase cost-effective dissemination of DMH training.(Disaster Med Public Health Preparedness. 2010;4:339-343)


2021 ◽  
Vol 12 ◽  
Author(s):  
Liu Qiao ◽  
Zhen Zhou ◽  
Xiaohui Zeng ◽  
Chongqing Tan

Objective: Camrelizumab is the first domestic PD-1inhibitor approved to be combined with chemotherapy as a first-line therapy for advanced nonsquamous non–small-cell lung cancer (NSCLC) in China. The purpose of this study was to determine whether using camrelizumab in the first-line setting is cost-effective in China when compared with traditional chemotherapy or the imported PD-1inhibitor pembrolizumab.Material and Methods: A Markov model was built to simulate 3-week patient transitions over a 30-year horizon from the perspective of the Chinese healthcare system. Health states included stable disease, first progression, second progression, and death. A direct comparison between first-line camrelizumab in combination with pemetrexed and carboplatin (CPC) and pemetrexed plus carboplatin (PC) was performed by calculating transition probabilities from the CameL trial. An indirect comparison between first-line CPC and pembrolizumab in combination with pemetrexed and platinum (PPP) was performed by calculating transition probabilities using a network meta-analysis. Costs in the Chinese setting were collected from the local public database and literatures. Sensitivity analyses explored the uncertainty around model parameters.Results: In the primary analysis, first-line CPC gained an additional 0.41 quality-adjusted life-years (QALYs) with an incremental cost of $3,486 compared with PC, resulting in an incremental cost-effectiveness ratio (ICER) of $8,378 per QALY gained. In the secondary analysis, first-line PPP yielded an additional 0.10 QALYs at an incremental cost of $6,710, resulting in an ICER of $65,563 per QALY gained.Conclusion: For Chinese patients with advanced nonsquamous NSCLC without targetable genetic aberrations, our primary analysis results supported first-line CPC as a cost-effective treatment compared with traditional PC chemotherapy. The findings of our secondary analysis suggested that first-line PPP would not be a cost-effective option compared with first-line CPC. This analysis provided strong evidence for promoting the widespread use of first-line CPC in China and, to some extent, stimulated the enthusiasm for the development of domestic cancer drugs.


Genetics ◽  
2007 ◽  
Vol 176 (4) ◽  
pp. 2611-2623 ◽  
Author(s):  
A. Korol ◽  
Z. Frenkel ◽  
L. Cohen ◽  
E. Lipkin ◽  
M. Soller

2017 ◽  
Author(s):  
Daniel Vodák ◽  
Susanne Lorenz ◽  
Sigve Nakken ◽  
Lars Birger Aasheim ◽  
Harald Holte ◽  
...  

Sample pooling enabled by dedicated indexes is a common and cost-effective strategy used in high-throughput DNA sequencing. Index misassignment leading to cross-sample contamination has however been described as a general problem of sequencing instruments which utilize exclusion amplification. Using real-life data from multiple tumor sequencing projects, we demonstrate that co-multiplexed samples can induce artifactual calls closely resembling high-quality somatic variant calls, and argue that dual indexing is the most reliable countermeasure.


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