Characteristics of patients with GBM – ASTRO- II- IV treated with CFRT+ HT
\r\n\tThe aim of this book will be to describe the most common forms of dermatitis putting emphasis on the pathophysiology, clinical appearance and diagnostic of each disease. We also will aim to describe the therapeutic management and new therapeutic approaches of each condition that are currently being studied and are supposed to be used in the near future.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"278931ae110500350d8b64805c70f193",bookSignature:"Dr. Eleni Papakonstantinou",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/7934.jpg",keywords:"Atopic eczema, Interleukin, Topical corticosteroids, Hand eczema, Blisters, Pruritus, Irritant contact dermatitis, Allergic contact dermatitis, Discoid eczema, Sebaceous glands, Inflammatory dermatitis, Facial rash",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 5th 2019",dateEndSecondStepPublish:"March 19th 2019",dateEndThirdStepPublish:"May 18th 2019",dateEndFourthStepPublish:"August 6th 2019",dateEndFifthStepPublish:"October 5th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"203520",title:"Dr.",name:"Eleni",middleName:null,surname:"Papakonstantinou",slug:"eleni-papakonstantinou",fullName:"Eleni Papakonstantinou",profilePictureURL:"https://mts.intechopen.com/storage/users/203520/images/system/203520.jpg",biography:"Dr. med. Eleni Papakonstantinou is a Doctor of Medicine graduate and board certified Dermatologist-Venereologist. She studied medicine at the Aristotle University of Thessaloniki, in Greece and she continued with her dermatology specialty in Germany (2012-2017) at the University of Magdeburg and Hannover Medical School, where she completed her dissertation in 2016 with research work on atopic dermatitis in children. During this time she gained wide experience in the whole dermatological field with special focus on the diagnosis and treatment of chronic inflammatory skin diseases and also the prevention and treatment of melanocytic and non-melanocytic skin tumors. Her research interests were beside atopic dermatitis and pruritus also the pathophysiology of blistering dermatoses. In addition to lectures at german and international congresses, she has published several articles in german and international journals and her work has been awarded with various prizes (poster prize of the German Dermatological Society for the project: 'Bullous pemphigoid and comorbidities' (DDG Leipzig 2016), 'Michael Hornstein Memorial Scholarship' (EADV Athens 2016), travel grant (EAACI Vienna 2016). Since 2017, she works as a specialist dermatologist in private practice in Dortmund, in Germany. Parallel she co-administrates an international dermatologic network, Wikiderm International and she writes a dermatology public guide for patients, as she is convinced that evidence-based knowledge has to be shared not only with colleagues but also with patients.",institutionString:"Private Practice, Dermatology and Venereology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"270941",firstName:"Sandra",lastName:"Maljavac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/270941/images/7824_n.jpg",email:"sandra.m@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"44350",title:"Glioblastomas, Astrocytomas: Survival Amelioration Adding Hyperthermia to Conformal Radiotherapy and Temozolomide — Use of Pegylated Doxorubicin and Hyperthermia in the Treatment of a Recurrent Case",doi:"10.5772/55966",slug:"glioblastomas-astrocytomas-survival-amelioration-adding-hyperthermia-to-conformal-radiotherapy-and-t",body:'Fifty per cent of primary brain tumours are Glioblastoma (GBM), the rest is constituted by astrocytomas and less aggressive tumours [1,2]. GBM is biologically an aggressive tumor quickly developing genetic hetereoneity and therapeutic resistance [2,3]. No specific markers exist for GBM at the moment as reported by Kesari [4], but new imaging techniques including diffusion weighted imaging (DWI), perfusion weighted imaging (PWI or MR), are aiding in better defining disease development and progression. According to the World Health Organization (WHO), astrocytomas are classified into four prognostic grades [4,5]. Grade I and two are classified as low grade gliomas whereas grade III and IV are classified as high grade gliomas, despite the fact that these grades indicate tumor aggressiveness they have not been reliable in predicting the response to therapy. Kesari has outlined that other factors such as overexpression of some growth factors and their receptors have prognostic relevance [4]. Overexpression of Platelet derived growth factor (PDGF) and its receptors indicates a tumor is less aggressive and has a better prognosis compared to GBM expressing the Epidermal Growth Factor (EGFR) [4,6].
Almost 45% of GBM have molecular alterations of the enzyme 06-methylguanine-DNA methyltransferase(MGMT) and mutations of isocitrate dehydrogenase 1 (IDH1) [7]. MGMT, affects signalling pathways and has an important role with alkylating cytostatic drugs such as Temozolomide (TMZ). Methylation of MGMT is associated to a better prognosis and response to TMZ [8]. More recently, a specific and target therapy has been suggested by authors such as Reardon and Wen [3] who have provided a complete list of these inhibitors for this disease including: Gefitinib (Iressa®), Ernolitib (Tarceva®),Thalidomide (Thalidomid®), Bezacizumab (Avastin®), and proteasome inhibitors (bortezomid).
Another approach at the moment not completely in use is immunotherapy [9, 10]. EGFR is expressed in near the 50% of patients with GBM [11]. Inhibitors of EGFR, like Iressa and Tarceva have been used with limited success [12]. A phase II study with Gefitinib has been conducted by Rich et al. in which fifty-seven patients have been treated orally once daily with 500 mg of oral Iressa®. No objective responses were seen, possibly because only 21% of patients had measurable disease at treatment initiation. Iressa® was well tolerated and a dose increase was thus suggested [13]. Studies with Tarceva® has given similar results with a minimum benefit not superior to standard treatment of care with radiotherapy and TMZ [14]. Another modest response has been obtained inhibiting the PDGF receptors using imatinib (Gleevec®) [10, 16].
Lasty, as angiogenesis due tumor hypoxia is a common processes in GBM [17,18], the inhibitor of Vascular Endothelial Growth Factor (VEGF) bevacizumab (Avastin) has been studied extensively in treating resistant GBM [17, 19]. Avastin has recently been used as single agent or in combination with several drugs, such as carboplatin [20], Ectoposide [21], Lomustine and TMZ [17]. Avastin, is a recombinant monoclonal immunoglobulin able to inhibit VEGF and to normalize tumor vasculature [21,22], but, the promises on GBM have not been confirmed and 98.8% of patients experienced adverse effects such as fatigue, headache, hypertension, thromboembolism, cerebral haemorrhage, convulsion and infarction [22]. Another antiangiogenetic factor Thalidomide has been used in GBL [23]. Thalidomide exert its anti tumoral activity through several mechanisms, such as: inhibition of angiogenesis, cytokine-mediated pathways and adhesion molecules modulation, inhibition of cyclooxygenase-2 and stimulation of immuno response [24]. Another approach is immunotherapy. As known GBL is an immunogenic tumor exerting an immunosuppressive effects on cell mediated immunity partially by regulatory T cells [25,26,27]. This kind of therapy is however experimental and dependent on laboratory skilled personal.
However, none of these association are really superior to TMZ + radiotherapy, regarding survival, and are also becoming cost - prohibitive [28]. Understanding this issue we have started to add hyperthermia (HT) to TMZ and Conformal Radiotherapy (CRT). The basis for adding HT together radiotherapy have been described since 2006 [29]. Hypoxia, the increased apoptosis induced by heat and the additive response to CRT are the most important reasons for adding HT in the treatment of GBM [29]. Animal and human studies have also indicated that there are significant chemosensitizing effects of adding HT to chemotherapy such as nitrosureas derivates [29, 30]. Previous studies not yet published by our group have shown that HT with TMZ is additive. We have thus be (TMZ) (5F,11 M median age 44.64 ± 9.95 yr), and were eligible to be compared with 15 patients with (GBM) treated with CFRT plus TMZ (see table 2)( 15 GBM, 7F,8M; 52.13±16.17 yr). Four of them (Astrocytoma IV ) were previous treated with CCNU, with disease progression (see. Table. 1). All patients had a histological proven malignant GBM or anaplastic astrocytomas. Since 2001, we have begun to use capacitive HT in association to TMZ and conformal radiotherapy. Follow up of patients was collected at a mean interval of 65 days, with a large range [40-90] days for those patients with a disease stabilization.
PTS | \n\t\t\tYear | \n\t\t\tGender | \n\t\t\tHistology | \n\t\t\tTMZ | \n\t\t\tCCNU | \n\t\t\tECOG | \n\t\t\tGy | \n\t\t\tRTV | \n\t\t\t\n\t\t\t\tNer HT\n\t\t\t\t Cycle | \n\t\t\tA/D | \n\t\t\t\n\t\t\t\tSurvival\n\t\t\t\t Ms | \n\t\t
1 | \n\t\t\t36 | \n\t\t\tF | \n\t\t\tGBM | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | 45 | \n\t\t\t65.6 | \n\t\t\t2 | \n\t\t\tD | \n\t\t\t25 | \n\t\t
2 | \n\t\t\t52 | \n\t\t\tM | \n\t\t\tGBM | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | 42 | \n\t\t\t101 | \n\t\t\t1 | \n\t\t\tD | \n\t\t\t12 | \n\t\t
3 | \n\t\t\t54 | \n\t\t\tF | \n\t\t\tGBM | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | 60 | \n\t\t\t\n\t\t\t | 1 | \n\t\t\tA | \n\t\t\t75 | \n\t\t
4 | \n\t\t\t57 | \n\t\t\tM | \n\t\t\tGBM | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | 14 | \n\t\t\t42 | \n\t\t\t3 | \n\t\t\tA | \n\t\t\t51 | \n\t\t
5 | \n\t\t\t51 | \n\t\t\tM | \n\t\t\tGBM | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | 20 | \n\t\t\t57 | \n\t\t\t2 | \n\t\t\tA | \n\t\t\t20 | \n\t\t
6 | \n\t\t\t45 | \n\t\t\tF | \n\t\t\tGBM | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | 65 | \n\t\t\t43.4 | \n\t\t\t1 | \n\t\t\tA | \n\t\t\t20 | \n\t\t
7 | \n\t\t\t70 | \n\t\t\tM | \n\t\t\tGBM | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | 28 | \n\t\t\t28.4 | \n\t\t\t5 | \n\t\t\tA | \n\t\t\t96 | \n\t\t
8 | \n\t\t\t31 | \n\t\t\tM | \n\t\t\tGBM | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | 14 | \n\t\t\t64 | \n\t\t\t1 | \n\t\t\tD | \n\t\t\t7 | \n\t\t
9 | \n\t\t\t41 | \n\t\t\tF | \n\t\t\tGBM | \n\t\t\t\n\t\t\t | \n\t\t\t | 3 | \n\t\t\t41 | \n\t\t\t64 | \n\t\t\t1 | \n\t\t\tD | \n\t\t\t12 | \n\t\t
10 | \n\t\t\t33 | \n\t\t\tM | \n\t\t\tGBM | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | 28 | \n\t\t\t28.4 | \n\t\t\t2 | \n\t\t\tA | \n\t\t\t83 | \n\t\t
11 | \n\t\t\t60 | \n\t\t\tF | \n\t\t\tGBM | \n\t\t\t\n\t\t\t | \n\t\t\t | 1 | \n\t\t\t65 | \n\t\t\t64 | \n\t\t\t1 | \n\t\t\tD | \n\t\t\t12 | \n\t\t
12 | \n\t\t\t40 | \n\t\t\tF | \n\t\t\tAstro IV | \n\t\t\tX | \n\t\t\tX | \n\t\t\t10 | \n\t\t\t25 | \n\t\t\t72.5 | \n\t\t\t1 | \n\t\t\tD | \n\t\t\t9 | \n\t\t
13 | \n\t\t\t43 | \n\t\t\tM | \n\t\t\tAstro IV | \n\t\t\tX | \n\t\t\tX | \n\t\t\t2 | \n\t\t\t47.6 | \n\t\t\t33.6 | \n\t\t\t2 | \n\t\t\tD | \n\t\t\t7 | \n\t\t
14 | \n\t\t\t59 | \n\t\t\tM | \n\t\t\tAstro IV | \n\t\t\tX | \n\t\t\tX | \n\t\t\t4 | \n\t\t\t45 | \n\t\t\t32.9 | \n\t\t\t1 | \n\t\t\tA | \n\t\t\t19 | \n\t\t
15 | \n\t\t\t37 | \n\t\t\tM | \n\t\t\tAstro IV | \n\t\t\t\n\t\t\t | X | \n\t\t\t1 | \n\t\t\t42 | \n\t\t\t101 | \n\t\t\t1 | \n\t\t\tD | \n\t\t\t12 | \n\t\t
16 | \n\t\t\t45 | \n\t\t\tF | \n\t\t\tAstro IV | \n\t\t\t\n\t\t\t | \n\t\t\t | 1 | \n\t\t\t44 | \n\t\t\t113 | \n\t\t\t1 | \n\t\t\tA | \n\t\t\t98 | \n\t\t
17 | \n\t\t\t44 | \n\t\t\tM | \n\t\t\tAstro IV | \n\t\t\t\n\t\t\t | \n\t\t\t | 10 | \n\t\t\t39.6 | \n\t\t\t\n\t\t\t | 3 | \n\t\t\tA | \n\t\t\t82 | \n\t\t
18 | \n\t\t\t44 | \n\t\t\tM | \n\t\t\tAstroII | \n\t\t\t\n\t\t\t | \n\t\t\t | 10 | \n\t\t\t45 | \n\t\t\t65.6 | \n\t\t\t4 | \n\t\t\tA | \n\t\t\t111 | \n\t\t
19 | \n\t\t\t34 | \n\t\t\tM | \n\t\t\tAstroII | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | 39.6 | \n\t\t\t44 | \n\t\t\t1 | \n\t\t\tD | \n\t\t\t23 | \n\t\t
20 | \n\t\t\t44 | \n\t\t\tF | \n\t\t\tAstroII | \n\t\t\t\n\t\t\t | \n\t\t\t | 10 | \n\t\t\t43 | \n\t\t\t112 | \n\t\t\t6 | \n\t\t\tD | \n\t\t\t17 | \n\t\t
21 | \n\t\t\t34 | \n\t\t\tM | \n\t\t\tAstroII | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | 45 | \n\t\t\t\n\t\t\t | 1 | \n\t\t\tA | \n\t\t\t76 | \n\t\t
22 | \n\t\t\t40 | \n\t\t\tF | \n\t\t\tAstro II | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | 4 | \n\t\t\tD | \n\t\t\t12 | \n\t\t
23 | \n\t\t\t30 | \n\t\t\tM | \n\t\t\tAstro II | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | 6 | \n\t\t\tA | \n\t\t\t60 | \n\t\t
24 | \n\t\t\t46 | \n\t\t\tM | \n\t\t\tAstro II | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | 6 | \n\t\t\tA | \n\t\t\t30 | \n\t\t
25 | \n\t\t\t46 | \n\t\t\tM | \n\t\t\tAstro II | \n\t\t\tX | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | 9 | \n\t\t\tA | \n\t\t\t17 | \n\t\t
\n\t\t\t\t25>\n\t\t\t | \n\t\t\t\n\t\t\t | \n\t\t\t\t9F- 16M\n\t\t\t | \n\t\t\t\n\t\t\t\t11GBM, 6 Astro IV, 8 Astro II\n\t\t\t | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t\t39.9±14.39\n\t\t\t | \n\t\t\t\n\t\t\t\t62.91±27.95\n\t\t\t | \n\t\t\t\n\t\t\t | \n\t\t\t\t13A-12D\n\t\t\t | \n\t\t\t\n\t\t\t\t39.44±34.25\n\t\t\t | \n\t\t
Characteristics of patients with GBM – ASTRO- II- IV treated with CFRT+ HT
Pts: Patients; GBM: Glioblastomas, Astro: Astrocytomas; RTV: radiotherapeutic volume; Gy: Gray; D: dead, A: Alive; Ms: months
Computer tomographic (CT) scans using a spiral CT scanner and magnetic resonance scanner (MR) were performed on each patients. These scans are elaborated for determining the cancer size and shape in 3 dimensions (3D). In this way precisely focused, high dose, radiation beams can be delivered to cancer mass in multiple treatment sessions. Before radiation, patients are fitted with a head frame, meantime CT and MR scans are performed to determine treatment planning. After the acquisition of these informations, patients are positioned on treatment couch and the linear accelerator directs arcs of radioactive photon beams to tumor. The pattern of the arc is computer - matched to the tumor shape using specific multileaf collimators. The CT/MR data of patients are sent to a computerized treatment platform. Through, this platform CT/MR images are fused using an image fusion software and the CTV is defined and contoured manually by clinicians and physicists. In our department, an integration of images with metabolic information such as single photon emission computed tomography (SPECT) has also been used. This permits sometimes to obtain a more accurate tumor visualization. The fusion of images is obtained by a commercial software package (Ergo- 3Dline®). Obtained the CTV, normally, a margin over these countered borders must be defined to take into account the possible microscopic extension of the tumour not evidenced on the CT/MR scans. These margins are generally countered 10-30 mm around the CTV obtaining the planned target volume (PTV). After PTV determination a new contour is done ensuring PTV coverage by 95% isodose line with the aim for obtaining a uniform dose homogeneity. Treatment is performed using a Varian Clinac 2100, 6mv. The median dose used for GBM and anaplastic astrocytomas treated with HT were of 36.87±17.75 Gy versus 39.2 ± 15.57 Gy for patients treated with CFRT+TMZ alone. The radiotherapeutic volume were 54.04 ± 22.53 mm3 versus 85.12 ± 50.37 mm3 respectively.
For treating our patients we used a device (Synchrotherm) developed by Duer ®, Vigevano, Italy. This device consists of the following components: 1) a Radiofrequency generator (13.56 Mhz) 2) a pair of mobile plates or electrodes with independent superficial cooling system, 3) a heat exchanger, 4) a computerized control console. The thermal profiles to obtain a probable deposition of the energy were obtained by heating patterns produced in a static phantoms. A cylindrical phantom made of 4% agar gel plus 02% NaCl was made and the various isotherms were monitored and reconstructed through computerizations of images obtained by a special film sensible to temperature. A flexible vinyl sheet, forming a space filled with 0.4% NaCl solution, covered the surfaces of the electrodes. The saline solution circulated between the electrode and the heat exchangers. Differently to other cooling system, the two electrodes were independently controlled and were simply adaptable to the contour of the brain patients, thanks to their flexibility These plates are coupled to opposite side of the patient ‘s brain and kept in place thanks to a girdle permitting a better contact over the irregularity of the skull contour. Capacitive hyperthermia treatment were given to the patients 30 ‘ after the CFRT; during the HT session 500cc of mannitol at 19%, plus 4-8 mg of desamethazone were infused. HT treatments lasted for all patients 1 hour, and for five days consecutively. Some of these patients received more than one HT treatment/month (median 3 maximum 5 HT treatments).
TMZ was administered orally 200mg/m2 /day on day one to five, after written informed consent. A full blood examination was performed before each new cycle. The treatment cycles were repeated every 28 days. The patients fasted 4 hours before TMZ use, and were submitted to conformal radiotherapy (CFRT), following our standards supplementation with omega-3 fatty acids and silymarin for preventing radionecrosis.
Temozolomide is an imido-tetrazine readily absorbed orally and able to cross the Blood brain barrier. TMZ has demonstrated activity against Glioblastoma, astrocytoma of various degree and brain metastases [3, 15]. Although TMZ has become the drug of choice in association with radiotherapy for Glioblastoma, many Glioblastoma develop resistance to the drug and become incurable. The reasons for this resistance is at the moment not completely understood and seems linked to the presence of certain subpopulations of cancer- stem cells inside the tumor mass [32]. This possible resistance has forced our group to look for other drugs active on GBM. We have chosed liposomal doxorubicin for various reasons that we will be describe here.
Liposomal doxorubicin (Caelyx®), is a formulation of hydrochloride doxorubicin wrapped by a film composed by phospholipids and polymers of methoxypolyethylene (mPEG) embedded in the lipid surface [33]. This association determines favorable pharmacokinetic profile characterised by an extended circulation time, a reduced volume of distribution, thereby promoting an increased tumour uptake [34, 35]. Tumor abnormal microcirculation and permeability is responsible for the increased uptake and retention of liposomal drugs, see Maeda [36]. This phenomenon is greatly increased by Hyperthermia, as demonstrated by Ponce and Dvorak [37, 38]. Dvorak was one of the first to use the combination of Caelyx® and hyperthermia on hepatocarcinoma and after his study reported that the combination of hyperthermia and doxorubicin itself may be supra-additive, resulting in enhanced antitumor efficacy in the heated region and in decrease of toxicity [38]. Caelyx® has been investigated by Koukoukaris in glioblastoma and in metastatic brain tumours [39]. These authors in agreement with Chua and Lesniak group concluded that liposomal doxorubicin selectively overcome the blood brain barrier and accumulate 13-19 times higher in the Glioblastoma [40, 41]. Furthermore, Chua [40] has demonstated the possibility of using Caelyx® in association with temozolomide in recurrent Glioblastoma. Liposomal doxorubicin was associated with disease stabilization and a modest haematologic toxicity. These studies have convinced our group to use pegylated doxorubicin in a recurrent case of GBM. The case is here briefly described.
The patient (right handed man) was first surgically treated (Dec 2005) for left posterior parietal Glioblastoma then the patient underwent RT (45 Gy CFRT in 18 fractions followed by a boost CFRT to reduced target of 20 Gy in 4 fractions) and started and continued Temodar (10 cycles) until progression (Jan 07) followed by ACNU (2 Cycles) until progression (March 2007) and then we started LD and Radiofrequency Hyperthermia (HT).
During the first period the cycles were done at 45 days interval then, after a initial good response and stabilization, the treatment was done at larger interval up to 9 CT+HT (the last treatment was done in Nov 2007).
The treatment was as follows: 12 mgm2 IV + steroids in glucose solution and assumption of 200 mg of Quercetin in day 1 and one hour of HT at least four hour later. From day 2 to 5 the patient underwent 4 further consecutive days of HT and quercetin (100 mg before and after the completion of treatment).
HT was delivered by means of a 13.56 MHz radiofrequency capacitive device (Synchrotherm Duer) via two opposite plates at the maximum tolerated power for at least one hour for five consecutive days.
Survival curves were calculated according to Kaplan-Meier method, Starting on the first day of HT. Survival was compared using the log-rank test and the K-test. Significance was posed as p ≤ 0.05 [11].
As it is possible to see comparing table 1 and table 2 there is no statistical difference between the two groups regarding age, gy administered and volume of tumour treated. The difference on survival curves (see Fig. 1) using the log-rank test and the K-test are important and more than the 50% of patients treated with CFRT+HT+TMZ are alive at 26 months. We can object than the comparison of the two groups is not completely homogeneous. In fact, the group in table 2 treated with TMZ + CFRT are only GBM, on the contrary in table 1 there is the presence of Astrocytoma of II degree. At a second look at table 1, an important observation emerges however, the GBM group has a long survival that is sometimes 3 times that of table 2, see pts 1, 3 table 2 and pts 3,7,10 of table1. It seems clear that HT adds something regarding survival and no side effects have been reported by patients. The patient treated with Caelyx® after surgery Dec 2005, had progression of the disease. He received CFRT in February 2006 and 10 cycles of Temodal. The patient on March 2009 shows progression and possible resistance to Temodal, we decided to treat the patient with 11 cycles of Caelyx + HT. The patient situation is illustrated in Fig 1( progression of disease after 10 cycle of Temodal, 2006) and Fig 2 after 11 cycles of Caelyx + HT (2009). The decrease of volume is evident. The patient is still alive and in treatment with a dose of 80 mg of Talidomide taken orally at evening, as a single dose.
Pts | \n\t\t\tGender | \n\t\t\tAge | \n\t\t\tRTV(cm3) | \n\t\t\tGy | \n\t\t\tD / A | \n\t\t\tMs Survival | \n\t\t
1 | \n\t\t\tF | \n\t\t\t30 | \n\t\t\t31.6 | \n\t\t\t36.4 | \n\t\t\tD | \n\t\t\t30 | \n\t\t
2 | \n\t\t\tM | \n\t\t\t52 | \n\t\t\t65.4 | \n\t\t\t20 | \n\t\t\tD | \n\t\t\t13 | \n\t\t
3 | \n\t\t\tF | \n\t\t\t64 | \n\t\t\t108 | \n\t\t\t40.5 | \n\t\t\tD | \n\t\t\t37 | \n\t\t
4 | \n\t\t\tM | \n\t\t\t22 | \n\t\t\t56.8 | \n\t\t\t25 | \n\t\t\tD | \n\t\t\t9 | \n\t\t
5 | \n\t\t\tM | \n\t\t\t69 | \n\t\t\t76.9 | \n\t\t\t45.6 | \n\t\t\tD | \n\t\t\t15 | \n\t\t
6 | \n\t\t\tM | \n\t\t\t57 | \n\t\t\t64.1 | \n\t\t\t70 | \n\t\t\tD | \n\t\t\t1 | \n\t\t
7 | \n\t\t\tF | \n\t\t\t61 | \n\t\t\t175 | \n\t\t\t18 | \n\t\t\tD | \n\t\t\t2 | \n\t\t
8 | \n\t\t\tF | \n\t\t\t65 | \n\t\t\t64.5 | \n\t\t\t35 | \n\t\t\tD | \n\t\t\t10 | \n\t\t
9 | \n\t\t\tF | \n\t\t\t47 | \n\t\t\t19.8 | \n\t\t\t54 | \n\t\t\tD | \n\t\t\t25 | \n\t\t
10 | \n\t\t\tM | \n\t\t\t66 | \n\t\t\t136.9 | \n\t\t\t45.5 | \n\t\t\tD | \n\t\t\t4 | \n\t\t
11 | \n\t\t\tM | \n\t\t\t50 | \n\t\t\t226 | \n\t\t\t42 | \n\t\t\tD | \n\t\t\t13 | \n\t\t
12 | \n\t\t\tF | \n\t\t\t45 | \n\t\t\t19.9 | \n\t\t\t54 | \n\t\t\tD | \n\t\t\t19 | \n\t\t
13 | \n\t\t\tM | \n\t\t\t67 | \n\t\t\t67.9 | \n\t\t\t20.4 | \n\t\t\tD | \n\t\t\t26 | \n\t\t
14 | \n\t\t\tM | \n\t\t\t65 | \n\t\t\t119 | \n\t\t\t20 | \n\t\t\tD | \n\t\t\t14 | \n\t\t
15 | \n\t\t\tF | \n\t\t\t22 | \n\t\t\t45 | \n\t\t\t45 | \n\t\t\tD | \n\t\t\t5 | \n\t\t
15 | \n\t\t\t7F- 8M | \n\t\t\t52.13±16.177 | \n\t\t\t85.12±50.37 | \n\t\t\t39.2±15.57 | \n\t\t\t15 D | \n\t\t\t14.87±10.7 | \n\t\t
Characteristics of Patients with GBM treated with CFRT + TMZ
Pts: Patients; RTV: radiotherapeutic volume; Gy: Gray; D: dead, A: Alive; Ms: months
Survival curve of patients treated with HT + CFRT + Temodal, compared with CFRT + Temodal
a. Patient with recurrent and drug resistance before Hyperthermia and Caelyx treatmen. b. Decrease of GBM volume after Hyperthermia and Caelyx treatment
Our study, is in agreement with the previous studies on HT [29], and show that the association with themozolomide is feasible and that this triple treatment (Chemotherapy, Conformal Radiotherapy and hyperthermia) represents a promising new approach to the treatment of glioblastomas. In this initial work we have not analyzed patients treated with hyperthermia without TMZ, so we cannot understand if the increase in life survival must be ascribed simply to HT or to the combination with temozolamide. The quantity of patients is limited but we are encouraged to use external capacitive HT in association with the standard therapy of our institution. In a near future, we hope to be able to distinguish the effects of the two therapies. We hope also to analyze the compliance of the patients to hyperthermia and to be able to study the side effects of HT on brain. We want to point out that most of works done on brain and hyperthermia regards studies with interstitial HT [29]. Interstitial HT represents to our opinion a limit to a larger use of this technique in association with CFRT and chemotherapy, whereas capacitive HT show a simpler use and seems to be well tolerated by patients.
In the coming years, agricultural production will have to face a double challenge, meeting the growing needs of the world’s population while preserving the environment and natural resources. According to [1], the world’s current population of about 6.3 billion people will reach nearly 8.6 billion in 2030. Agricultural production will then have to be significantly higher. This will be achieved by increasing yields. This has been achieved mainly through varietal improvement and associated cultivation techniques, including nitrogen fertilization.
In Algeria, 20% of the agricultural potential is located in the north of the country, which is characterized by poorly fertile soils. These soils are low in nutrients and have a very low rate of organic matter. Fertilization has remained archaic in the country. According to [2], in Algeria, the use of fertilizers in agriculture is not under control, despite the efforts made by farmers in charge of the cereal intensification program and potato farmers.
According to [3], fertilizers are applied in the absence of technical standards, neglecting the initial soil content; consequently, inputs are often poorly fractioned, leading to waste, which is a source of soil and water pollution. As several researchers have shown in their work on Algerian soils. In this context, [4, 5] conducted trials in the same semi-arid climate, respectively, on durum wheat and barley seed production, obtained maximum yields with similar rates (150 kg N/ha). These yields reached the respective values of 33.82 and 33.25 q/ha, i.e. gains of 11.52 and 9.76 q/ha. [6] showed that the interaction of potassium (P) and nitrogen (N) fertilization significantly affects wheat grain yield in the Saharan zone. The maximum yield reached 6.780 Mt./ha with the N250 P180 dose. With regard to nitrogenous fertilization, the observation highlights the need to promote adapted and balanced fertilization. Since urea is the most widely used nitrogen fertilizer in the world [7], it is crucial to assess the nitrogen use efficiency (NUE) by crops, since it is always aimed at achieving higher yields with a minimum application of fertilizer. This indicator (NUE) has been widely studied by several researchers around the world on various crops, including cereals, e.g. rice [8], maize [9], durum wheat [10, 11]; leafy vegetables, e.g. lettuce [12, 13, 14], spinach [15], cabbage [16] and vegetable crops, e.g. Potato [17, 18]; beans [19], tomato [20, 21].
In this perspective, this study uses the isotope approach 15 N to evaluate the nitrogen use efficiency. This new method, used by [22], highlights 15 N isotopic nitrogen, which is the most commonly used stable isotope in agriculture-related studies. It is the direct way to measure nitrogen uptake by applied fertilizer, and the most reliable way to monitor the flow and fate of nitrogen in the soil–plant system [23, 24]. To highlight the monitoring of this system, the chosen plant material is lettuce (Lactuca sativa L.), due to its short growing cycle. But also, because of the socio-economic impact that is beginning to dominate, at the national level. It is a source of wealth and income for producers. The search for decision support tools is essential in order to master agricultural practices and to plan for a sustainable agriculture that respects the environment. In this respect, the AquaCrop model, designed by the FAO, has been chosen as a decision support tool. The objective of this study is essentially oriented toward the search for optimum doses of nitrogenous fertilizers with the aim of contributing to the production of technical references for the efficient use of fertilizers.
The study was conducted at the National Institute of Agronomic Research of Algiers (36°68′ N and 3°1′ E, at an altitude of 18 m), located south-west of Algiers in the eastern part of the Mitidja (Figure 1).
Location of the study area.
Climatic conditions in the study area are characterized by pronounced seasonal variations with mild, wet winters and hot, dry summers. The meteorological data used are from the automatic weather station installed in the field. The measurements taken at daily time steps are: minimum and maximum temperatures (°C), rainfall (mm), wind speed (m/s) at 2 m above ground level, solar radiation (W/m2) and relative humidity (%). The reference evapotranspiration (ET0) was calculated according to the FAO Penman-Monteith method [25]. A soil profile was carried out over a depth of one meter, comprising three horizons. Soil samples were taken from each horizon with an auger for analysis physico-chemical.
The crop taken into consideration is variety lettuce, stubborn from Nîmes, belonging to the lettuce to be applesauce class, which is eaten young, before it goes to seed. Lettuce seeds were sown in the honeycomb plates for 19–25 days in the nursery before being transplanted. The young lettuce plants were transplanted at the 3–4 leaf stage onto well plowed soil in the field.
The experiment was carried out in the open field using a complete randomized block experimental design with four levels of nitrogen, namely: T1 (0 N kg/ha), T2 (60 N kg/ha), T3 (120 N kg/ha) and T4 (180 N kg/ha) arranged in four blocks. Each block has four sub-plots. Each micro plot is 6 m long and 3 m wide, giving a total area of 18 m2, of which 4.5 m2 was used for the 15 N. The trial was repeated for two consecutive years (2014–2015) and (2015–2016). Isotopic nitrogen was used only in the first year because of its high cost. The amounts of nitrogen used were distributed along the crop development cycle, namely: 10% at 15 days after transplanting (DAT), 30% at 40 DAT, 40% at 60 DAT and 20% at 75 DAT. The growing season is from January to April for both companions, coinciding with the winter season, during which irrigation is not necessary.
The parameters measured in the field are essentially the above-ground biomass (B), which represents a parameter that best allows verification of fertilizer efficiency in lettuce where the growth of the above-ground part is a determining factor in agricultural value [26]. Every 10 days, samples of 6 plants/subplot are taken and brought back to the laboratory where they are dried in the open air for 24 h and then in an oven for 48 h at 70 C°. In addition to this, the evolution of the green canopy (CC) cover is monitored by reference to photos taken vertically at a height of 1.8 m above the crop, using a photometric device. The photos were analyzed using ARCgis 10.1 software using the supervised classification by maximum likelihood method (Figure 2). Harvesting was done when the apples were tightly packed and full for each subplot of 1 m × 1 m.
Analyses of the fraction of the green canopy for the growth stage.
To determine the isotopic composition of lettuce plants, lettuce heads receivingan15N were divided into two parts (roots and leaves). Fresh weight was assessed for all parts of the crop. The samples were dried at 70°C for 24 hours, weighed for dry weight determination, ground into a fine powder using a 0.3 mm sieve and homogenized for total nitrogen and excess N15. The isotopic analysis of the lettuce culture samples was carried out at the National Centre for Energy, Science and Nuclear Techniques (CNESTEN-Morocco).
The quantification of fertilizer nitrogen was measured on the basis of the isotope dilution method from fertilizer nitrogen and the rate of nitrogen fertilizer applied, according to the following equation defined by [22]:
AquaCrop requires five important components to be functional: climate, with its thermal regime, rainfall, evaporative demand (ETP) and carbon dioxide concentration; then crop characteristics, including development, growth and yield formation processes (Table 1); then soil, with its hydraulic characteristics (hydraulic conductivity at saturation, moisture at saturation, field capacity and permanent wilting point); and finally management practices, which are divided into two categories: plot management and irrigation practice management; and finally initial conditions.
Description | Units | 2015–16 | Source |
---|---|---|---|
Conservative crop parameters | |||
Base temperature | C° | 7 | Calibrated |
Upper temperature | C° | 30 | Calibrated |
Upper threshold for canopy expansion, Pexp,upper | — | 0.25 | Simulated |
Lower threshold for canopy expansion, Pexp,lower | — | 0.55 | Simulated |
Shape factor for the stress coefficient for canopy expansion | — | 3 | Calibrated |
Upper threshold for stomatal closure, Psto,upper | - | 0.50 | Calibrated |
Shape factor for the stress coefficient for stomatal closure | — | 3 | Calibrated |
Water productivity (WP) | g m−2 | 19 | Calibrated |
Reference harvest index (HIo) | % | 95 | Measured |
Crop coefficient when canopy is complete | — | 0.85 | Simulated |
Non conservative parameters | 2015–16 | ||
Number of plants per m2 | Plant m−2 | 15 | Measured |
CC0 | % | 2.25 | Simulated |
Maximum canopy cover CCx | % | 81 | Measured |
Canopy size of the transplanted seedling | cm2 plant−1 | 15 | Measured |
Time from transplantation to emergence | Days | 7 | Observed |
Time from transplantation to senescence | Days | 80 | Observed |
Time from transplantation to maximum (CCx) | Days | 50 | Observed |
Time from transplantation to maturity | Days | 95 | Observed |
Minimum effective rooting depth | m | 0.20 | Measured |
Maximum effective rooting depth | m | 0.40 | Measured |
Transplantation time at maximum depth of rooting | Days | 55 | Observed |
Date of transplantation | 11/01/16 | ||
Harvest date | 14/04/2016 | ||
Canopy growth coefficient (CGC) | % days−1 | 14.30 | Simulated |
Canopy decline coefficient (CDC) | % days−1 | 8.0 | Simulated |
Input culture parameters to calibrate the AquaCrop model.
Calibration of the model to fertility stress requires coverage of the green canopy (CC) and biomass production (B), recorded on the fertility stressed plot ‘stressed plot’ and the unstressed plot ‘reference plot’ (Table 2). The soil fertility stress in the AquaCrop model is given as follows:
Treatments | Brel (%) | CCx under fertility level (%) | Canopy Decline (-) |
---|---|---|---|
T1 | 51 | 51 | Strong |
T2 | 73 | 55 | Medium |
T3 | 100 | 61 | Little |
T4 | 100 | 58 | Little |
Input data to calibrate the AquaCrop model for soil fertility stress.
Where: Brel is the ratio of total dry above-ground biomass at the end of the growing season in the reference plot (Bref) to that under stress (Bstress). Soil fertility affects water productivity (WP), canopy growth coefficient (CGC), maximum cover (CCx) and canopy senescence.
The evolution of canopy cover, dry above-ground biomass and yield were taken into account in the evaluation of the AquaCrop model, while using the following statistical indicators: the coefficient of determination (R2) of the linear fit, the square root of the normalized root mean square error (nRMSE) and the Willmott’s agreement index (d).
Variations in rainfall and ETP are shown in Figure 3, which illustrates the rainfall distribution during the two years of experience 2014–2015 and 2015–2016.The cumulative rainfall received between September and August is, respectively, of the order of 552 and 551 mm. Those corresponding to the experimental seasons (January to April), they are close to the averages of 211.4 and 303.4 mm. The corresponding potential annual evapotranspiration is of the order of 744.3 and 782.6 mm. Those corresponding to the growing seasons are, respectively, 195.4 and 196.5 mm.
Precipitation, potential evapotranspiration (ETP) on a monthly scale for test years 2014–2015 and 2015–2016.
The study site is characterized by deep and heavy soils with high clay content. Soil analysis revealed the existence of 3 horizons with a silty-clay texture with high clay rates increasing with soil depth. At profiles of 0–25 cm, 25–55 cm and beyond 55 cm depth, these rates are 43, 49, and 52%, respectively. The pH of the station soils is generally slightly basic at 7.8, CEC varies between 17.9 and 15 meq/100 g and total limestone has a rate between 7.9 and 7.8%. The organic matter rate is 1.57% on the surface and 0.49% at depth.
Figure 4 shows the evolution of the nitrogen doses applied at different phenological stages of the plant. This evolution is supported by the analysis of variance, which showed a very highly significant effect (p < 0.001), of the dry biomass, in relation to the increase in the doses of nitrogen supplied. A maximum of dry biomass is reached at the dose of 120 kg N/ha. Above this level, the increase in nitrogen rate is not significant. This result is consistent with that of [27], which showed that fertilization at high doses leads to a decrease in above-ground biomass. This is the case in the first year (2014–2015).
Effect of different levels of fertilization on the evolution of dry above-ground biomass for the two growing seasons.
Figure 5 shows lettuce yields as a function of applied nitrogen rates. In fact, the graph shows that, during the two experimental campaigns, the highest lettuce yields (55.24 and 57.96 t/ha) were obtained by applying the 120 and 180 kg/ha rates. These doses are very highly significant (p < 0.001) compared to those obtained (30.19 and 45.49 t/ha) by applying the minimum doses of less than 60 kg/ha. This result is consistent with those of [28, 29, 30], who reported that increasing the N level from 0 to 120 kg N/ha had a positive effect on lettuce production. Nevertheless, in detail, the T4 treatment from the 2014–2015 trial shows a relatively lower yield of 50.25 t/ha compared to the T3 treatment (54.25 t/ha) from the same year. The difference, evaluated at 3.08 t/ha, can be explained by the toxicity of the plants or by the nonattraction of nitrogen by the plants resulting from the consumption of excess nitrogen fertilizer, as pointed out by [31]. The response of lettuce for yields is considerably higher in 2016 than in 2015. This result is related to the higher rainfall amounts.
Effect of different levels of fertilization on yield for the two growing seasons.
Nitrogen Use Efficiency (NUE) is an important indicator in the application of nitrogen fertilizers. Achieving a higher NUE always becomes a priority in agriculture [8]. In this context, Figure 6 illustrates the variation in the percentage of NUE as a function of defined thresholds. For rates ranging from 60, 120 to 180 kg N/ha, the NUE varies from 65.42, 74.49 to 68.38%, respectively. The NUE decreased from 74.49% to 68.38% by increasing the rate from 120 to 180 kg N/ha. These results are similar to those reported by [32, 33]. The 120 kg N/ha rate provides the best efficiencies. This means that 74.48% of the fertilizer applied is consumed by the lettuce crop. The remaining 25.52% of N is either in the soil or lost through leaching. Lettuce is a short-cycle crop, making the best use of available nitrogen, as reported by [34].
Variation in nitrogen use efficiency by lettuce, expressed as a percentage (%).
Figure 7 shows the variation in water productivity (WP), soil evaporation (Es) and transpiration (Tr) of the lettuce crop under different levels of fertilization. This variation is supported by the analysis of variance, which showed a very highly significant effect (p < 0.001) of these parameters (WP, Es and Tr), in relation to the increase in the doses of nitrogen applied. The maximum values of WP and Tr are reached at the dose of 120 kg N/ha, for the two companions 2014–2015 (WP = 8.95 kg/m3; Tr =51.4 mm) and 2015–2016 (9.57 kg/m3; Tr = 55.80 mm). Above this level, the increase in the nitrogen rate is not significant.
Variation in water productivity of lettuce under different levels of fertilization.
Experimental results of yield, canopy cover and dry above-ground biomass under different levels of fertilization are presented in Table 3. The AquaCrop model (V. 6.1) was calibrated using the crop data set obtained from the T3 treatment (120 kg N/ha). The lowest dry yield and dry aboveground biomass observed were 4.021 t/ha and 4.125 t/ha under the T1 treatment (0 kg N/ha), and the highest were 8.854 t/ha and 9.320 t/ha under the T3 treatment (120 kg N/ha), respectively.
Treatments | Biomass (t/ha) | Dry yield (t/ha) | CCx (%) | |||||
---|---|---|---|---|---|---|---|---|
Obs | Sim | Obs | Sim | SD (±%) | Obs | Sim | SD (±%) | |
T1 | 4.125 | 4.785 | 4.021 | 4.546 | (6.70) | 51 | 44.80 | (1.68) |
T2 | 5.872 | 6.806 | 5.234 | 5.785 | (11.68) | 55 | 54.10 | (5.76 |
T3 | 7.969 | 9.320 | 7.834 | 8.854 | (8.27) | 61 | 63.90 | (2.67) |
T4 | 7.788 | 9.100 | 7.626 | 8.645 | (8.40) | 58 | 63.70 | (3.55) |
Biomass calibration results, yield, and maximum canopy cover under different levels of fertilization in 2015–2016.
The AquaCrop model is capable of simulating these parameters. Overall, the agreement between simulated and observed vegetation cover and biomass is satisfactory with 0.64 < R2 < 0.81, 18 < nRMSE > 46.3 and 0.78 < d < 0.94; 0.92 < R2 < 0.94, 21.6 < nRMSE <34.5, 0.91 < d < 0.96 (Table 4).
Indicators | CC (%) | Dry biomass (t/ha) | ||||||
---|---|---|---|---|---|---|---|---|
T1 | T2 | T3 | T4 | T1 | T2 | T3 | T4 | |
R2 | 0.81 | 0.71 | 0.66 | 0.64 | 0.92 | 0.98 | 0.94 | 0.94 |
NRMSE | 18 | 35.5 | 41.4 | 46.3 | 34.5 | 21.6 | 25.6 | 25 |
EF | 0.79 | 0.03 | −0.13 | −0.06 | 0.55 | 0.85 | 0.82 | 0.82 |
d | 0.94 | 0.81 | 0.78 | 0.80 | 0.91 | 0.96 | 0.96 | 0.96 |
Indicators of goodness of fit in estimating canopy cover and dry biomass.
Figure 8 shows the comparison between simulated and observed canopy cover (CC) and dry above-ground biomass (B) for the calibration period (2015–2016). This figure shows that there is a close correspondence between observed and simulated CC and B. It is also important to note that the AquaCrop model correctly simulates CC from seeding to the maximum growth phase at which CCx is reached. This observation has been reported in several studies [35, 36, 37]. From Figure 8, it is clear that both parameters (CC) and B were overestimated by the AquaCrop model. In a recent study [38], it was shown that the AquaCrop model overestimated the cabbage canopy under different irrigation regimes. [39] also noted a slight (10%) but systematic overestimation of the amount of rice biomass conducted under different levels of irrigation and fertilization.
Canopy coverage (a) and dry biomass (b) simulated and measured for the calibration period (2015–2016) under different fertilization levels (T1, T2, T3, and T4).
Observed and simulated lettuce yields are shown in Figure 9. The observed yields for treatments T1, T2, T3 and T4 are, respectively, 4.214; 5.187; 6.942 and 6.214 t/ha, while the simulated yields are 4.897; 5.981; 7.414 and 6.987 for the trial period (2014–2015), with a correlation coefficient R2 = 0.92. On the other hand, the yields observed and simulated under the four treatments for the trial period (2015–2016) are of the order of 4.021; 5.234; 7834 and 7.626 t/ha, while those simulated are of the order of 4.546; 5.785; 8.854 and 8.645, with a correlation coefficient R2 = 0.99. Analysis of statistical tests and linear regression indicated that the values simulated by the AquaCrop model are in good agreement with those observed. [40] reported R2 values >0.80 when simulating above-ground biomass and barley grain yield using AquaCrop.
Simulated and observed lettuce yields under different levels of fertilization.
The management of nitrogen fertilization is a major issue for agricultural production while contributing to water and soil pollution. In this situation, the adoption of fertilization management strategies aimed at using efficient doses and increasing the effectiveness of their use becomes necessary. Crop models simulating yield under such conditions could be important tools for fertilizer management planning. To this end, the parameterization of the AquaCrop model to estimate the effect of fertility constraints on lettuce yield under different levels of fertilization was investigated. The model tended to overestimate canopy coverage for T3 (120 kg N/ha) and T4 (180 kg N/ha) treatments, but with reasonable statistical indices (nRMSE: 14.80 for T3 and 12.50 for T4). AquaCrop has confirmed that it is a very useful tool that can be used to optimize the N rates applied to the crops, to play on the management of the plot in order to maximize yields.
IntechOpen publishes different types of publications
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