<div>AbstractPurpose:<p>Response to preoperative chemo-radiotherapy (CRT) varies. We assessed whether circulating tumor DNA (ctDNA) might be an early indicator of tumor response or progression to guide therapy adaptation in rectal cancer.</p>Experimental Design:<p>A total of 243 serial plasma samples were analyzed from 47 patients with localized rectal cancer undergoing CRT. Up to three somatic variants were tracked in plasma using droplet digital PCR. RECIST and MRI tumor regression grade (mrTRG) evaluated response. Survival analyses applied Kaplan–Meier method and Cox regression.</p>Results:<p>ctDNA detection rates were: 74% (<i>n</i> = 35/47) pretreatment, 21% (<i>n</i> = 10/47) mid CRT, 21% (<i>n</i> = 10/47) after completing CRT, and 13% (<i>n</i> = 3/23) after surgery. ctDNA status after CRT was associated with primary tumor response by mrTRG (<i>P</i> = 0.03). With a median follow-up of 26.4 months, metastases-free survival was shorter in patients with detectable ctDNA after completing CRT [HR 7.1; 95% confidence interval (CI), 2.4–21.5; <i>P</i> < 0.001], persistently detectable ctDNA pre and mid CRT (HR 3.8; 95% CI, 1.2–11.7; <i>P</i> = 0.02), and pre, mid, and after CRT (HR 11.5; 95% CI, 3.3–40.4; <i>P</i> < 0.001) compared with patients with undetectable or nonpersistent ctDNA. In patients with detectable ctDNA, a fractional abundance threshold of ≥0.07% mid CRT or ≥0.13% after completing CRT predicted for metastases with 100% sensitivity and 83.3% specificity for mid CRT and 66.7% for CRT completion. All 3 patients with detectable ctDNA post-surgery relapsed compared with none of the 20 patients with undetectable ctDNA (<i>P</i> = 0.001).</p>Conclusions:<p>ctDNA identified patients at risk of developing metastases during the neoadjuvant period and post-surgery, and could be used to tailor treatment.</p></div>
<p>In the Mediterranean region, climatic variations in conjunction to intensive agriculture deteriorates groundwater resources which are over-exploited to cover irrigation demands. A characteristic example is Messara Basin in the island of Crete, Greece. This work presents an integrated suitability assessment study for potential aquifer recharge that considers the availability of water resources, hydro-geological and geomorphological characteristics, climatic scenarios, soil properties and suitability, and socioeconomic analysis under the framework of a suitable aquifer recharge technique.</p><p>The most suitable technique for planning the aquifer recharge was selected according to the area characteristics. The spreading method was assessed as the most suitable technique based on the area characteristics that should typically have a source of excess water available nearby, be located in a relatively flat area with permeable soils and be underlined by an unconfined aquifer. A multi-criteria decision analysis method was applied to identify suitable sites for implementing aquifer recharge type spreading method. The methodology is based on a multicriteria matrix developed in accordance to a relative optimization (weighting) method in terms of hydrogeological and geomorphological criteria, and water availability (reservoir, river). Criteria combining a high relevance and high data availability, and providing unique information, selected to assess the suitability of aquifer recharge in Messara basin such as slope, land use, hydrogeology, rainfall, groundwater level, soil texture and distance to source water.</p><p>All the aforementioned factors were separately studied and analyzed and then were combined under the principles of the spreading method to provide by means of spatial maps the most appropriate locations in the study basin.</p><p>The outcome of this work is a simple framework methodology for selecting the most suitable recharge locations of the underlying aquifers and to demonstrate its socioeconomic and environmental advantages. The results of this work will assist local authorities to consider the applicability of aquifer recharge in the Messara valley while it consists a framework for efficient planning of similar applications in other Mediterranean regions.</p><p>&#160;</p><p>Acknowledgments</p><p>This work was implemented in the framework of the research project Uncertainty-aware intervention design for Mediterranean aquifer recharge. The project: "Uncertainty-aware intervention design for Mediterranean aquifer recharge benefits from the support of the Prince Albert II foundation". http://www.fpa2.org</p><p>&#160;</p><p>References</p><p>Special water secretariat of Greece, 2017. Integrated Management Plans of the Greek Watersheds, Ministry of Environment & Energy, Athens.</p><p>Varouchakis, E.A., 2016. Integrated Water Resources Analysis at Basin Scale: A Case Study in Greece. J. Irrig. Drain. E-ASCE 142(3), 05015012. DOI:10.1061/(ASCE)IR.1943-4774.0000966</p>
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