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1. Introduction
The lung cancer remains one of the most common cancers, and 80% of lung cancers account for non-small cell lung cancer (NSCLC) [1]. Patients diagnosed at a locally advanced stage represent 20 to 30%, and radical surgery is challenging for those patients [1]. Definitive chemoradiotherapy is a well-established treatment option for unresectable locally advanced NSCLC [2, 3]. Treatment outcomes in such patients have improved over the last few decades. Several treatment regimens have been shown to be effective and safe. Moreover, modern radiotherapy technologies have been developed along with the development of optimal chemotherapy and immunotherapy to improve outcomes and minimize radiation-induced toxicity. This chapter summarizes historical results of key clinical studies in the past in terms of various regimens of chemoradiotherapy. In addition, we discuss definitive radiotherapy, which is recommended for locally advanced NSCLC. Specifically, we address future perspectives of definitive radiotherapy for locally advanced NSCLC.
2. History of the development of definitive radiotherapy for locally advanced NSCLC
Radiotherapy alone was a standard treatment for inoperable lung cancer up to the 1980s based on the results of a randomized controlled trial in the 1960s [4]. Perez et al. showed the dose–response efficacy up to 60 Gy, which had been a standard dose from the combined results of the RTOG 7101 and 73–02 study [5]. After the 1990s, definitive radiotherapy, using ≥60Gy in a conventional fractionated regimen, combined with chemotherapy, has been used as a standard treatment for unresectable locally advanced NSCLC. In the early 1990s, sequential cisplatin-based chemotherapy followed by radiotherapy had been proven to have a survival benefit over definitive radiotherapy alone and chemotherapy alone for unresectable stage III NSCLC [6, 7, 8, 9]. Then, from the late 1990s to the 2000s, several randomized clinical trials revealed that the concurrent approach of chemoradiotherapy enhanced survival compared to the sequential approach [10, 11, 12, 13]. After 2000, the usefulness of several new agents, such as paclitaxel, gemcitabine, vinorelbine, and docetaxel, which are called third-generation chemotherapy agents, have been studied. They have been usually administered in combination with platinum compounds, and demonstrated increased survival in patients with metastatic NSCLC [14, 15]. Although there has been no significant improvement in survival achieved with chemoradiotherapy using third-generation regimens, it has become a standard treatment with a favorable toxicity profile [16, 17].
Some clinical studies conducted between 1990s and 2000s showed that hyperfractionated, accelerated radiotherapy was superior to the conventional fractionated radiotherapy with a feasible toxicity [18, 19, 20, 21]. However, the benefit of hyperfractionated, accelerated radiotherapy is controversial, with high risk of acute esophageal toxicity; and has been less accepted in clinical practice [2, 21, 22]. After 2000, the utility of consolidation chemotherapy following chemoradiotherapy has failed to prove a significant survival benefit [23, 24, 25]. A dose escalation of radiotherapy has been investigated because loco-regional tumor control might be associated with better survival; and there is a potential dose–response efficacy in the control of NSCLC using this approach [5, 26]. However, RTOG 0617 trial failed to prove benefits on overall survival (OS) and progression-free survival (PSF) using the escalated doses of 74 Gy compared to the standard dose of 60 Gy in an open-label randomized phase 3 study [27]. Volume prescriptions such as D95 using updated calculation algorithms in recent clinical trials could reveal a slightly escalated dose for the target, in comparison with the point prescription that has been used in previous studies. However, the standard regimen of definitive radiotherapy has been 60 Gy in 30 fractions.
As shown in Figure 1, the median survival time after treatment has improved with the development of chemoratiotherapy. However, the 5-year survival rate has been unsatisfactorily, reaching only up to 20%. Recently, immune checkpoint inhibitors (ICIs) have been applied in the treatment of advanced malignancies, including lung cancer [29]. ICIs block checkpoint proteins that can weaken immune responses by T cells to cancer cells. Recent systematic reviews have demonstrated the beneficial effects of ICIs on OS and PSF in advanced NSCLC [30]. The PACIFIC trial, a randomized, double-blind, placebo-controlled multi-center trial, has tested the efficacy of dulvalumab, which is a human monoclonal antibody directed against programmed cell death-ligand 1 (PD-L1), in patients with stage III NSCLC as sequential treatment following standard concurrent chemoradiotherapy [19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32]. Dulvalumab has brought a breakthrough in the treatment of locally advanced NSCLC in decades, and median survival after treatment has not reached with a median follow-up of 33.3 months in a recent updated result [28]. The transition of standard definitive radiotherapy for locally advanced NSCLN and representative of the clinical outcomes of selected prospective clinical trials with time are shown in Table 1 and Figure 1.
Figure 1.
Improvement of survival outcome of locally advanced NSCLN. (A) Median survival and (B) 3-year overall survival per selected prospective clinical studies and meta-analyses [4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 17, 23, 24, 27, 28]. Each bar indicates the mean value of the results. Radiotherapy group included locally advanced NSCLC patients who underwent treatment with standard radiation doses such as ≥60Gy in a conventional schedule. Abbreviations: Con-CRT, concurrent chemoradiotherapy; Con-CRT-ICI, concurrent chemoradiotherapy with consolidation immune checkpoint inhibitor; RT, radiotherapy; Seq-CRT, sequential chemoradiotherapy.
Concurrent chemoradiotherapy followed by immune checkpoint inhibitor (dulvalumab)
Table 1.
Transition of standard definitive radiotherapy for locally advanced NSCLN.
3. Utility of intensity-modulated radiotherapy, learning from RTOG 0617 and PACIFIC trials
RTOG 0617 trial failed to demonstrate the benefit of dose-escalation of 74 Gy compared with 60 Gy, but also provided significant information for clinical practice, as it was the first phase III NSCLC study to allow intensity-modulated radiotherapy (IMRT) as a treatment modality for locally advanced NSCLC, and 46% of enrolled patients underwent IMRT [27, 33].
The disadvantage of IMRT in terms of dose distribution is increased volume of lungs receiving low-dose radiation, called “low-dose bath” because the IMRT plan is created using the increased number of beam angles [34]. Low-dose baths represented by large volumes of lung V5 (the volume of the lungs receiving ≥5 Gy) has been reported to increase the risk of acute and late pulmonary toxicity [34, 35, 36]. IMRT was used to treat larger and unfavorable tumors in RTOG 0617 [37]. Lung V5 was significantly higher in the IMRT group than in the 3D-CRT group. However, IMRT was associated with lower rates of severe pneumonitis in the RTOG 0617 prospective clinical trial. In addition, severe pneumonitis was predicted by lung V20, but not V5. Thus, V20 has been confirmed as a well-established risk factor of radiation pneumonitis with high reproducibility [38]. It is difficult to clarify the controversial meaning of V5 as a predictor of radiation pneumonitis. However, IMRT could improve target coverage and reduce the volume of normal lungs irradiated with intermediate doses such as V20 [34]. Grade ≥ 2 pneumonitis after chemoradiotherapy was a significant exclusion criterion in the PACIFIC trial [31]. The reduction of the risk of radiation pneumonitis by using IMRT might maximize the opportunity of receiving consolidation ICI based on the PACIFIC trial, although detailed data on radiotherapy was not collected in the PACIFIC trial [28, 31, 32, 37].
Higher doses to heart and esophagitis were associated with poor survival [37, 39]. In patients receiving heart V50 < 25% versus ≥25, the 1-year OS rates were 70.2% versus 46.8% and the 2-year OS rates were 45.9% versus 26.7% (p < 0.0001) [39]. Heart V40, which has been shown to be a prognostic factor for survival, can be substantially reduced with IMRT compared to 3D-CRT. In addition, the use of IMRT was associated with significantly less decline in quality of life [40]. These toxicities were potentially associated with poor survival in patients treated with escalated radiation doses of 74 Gy [27]. Furthermore, the correlation of institution accrual volume with the treatment outcomes is controversial but can be associated with other malignancies such as head and neck cancers [39, 41, 42, 43]. Quality assurance and institutional experience seem important in radical treatment of locally advanced NSCLC.
The benefits of proton therapy have been reported and included a better dose distribution to the lung and heart in treatment plan than in photon radiotherapy [44]. A randomized control study that compared the utility of proton therapy with that of IMRT showed no significant benefit in terms of the occurrence of radiation pneumonitis and local failure [45]. Modern proton techniques might improve clinical outcomes, but there is no significant evidence of a superiority of proton therapy over IMRT at this moment.
IMRT allows the treatment of challenging cases with dosimetric and clinical benefits. Therefore, IMRT is a current standard technique in the definitive radiotherapy for advanced NSCLC, as the use of IMRT has various advantages over 3D-CRT, which obviously outweighs the disadvantages.
4. Tips for using definitive radiotherapy for locally advanced NSCLC
4.1 Involved-field radiotherapy
The European Society for Radiotherapy and Oncology recommends that metastatic nodes and the applicable margin with no further elective lymph nodes should be included in clinical tumor volume (CTV) [46]. Radiotherapy has been prescribed to the intersection point of the treatment beams [18]. An initial radiotherapy was administered to the anteroposterior parallel–opposed pair of portals and then to a pair of oblique fields during the boosted radiotherapy [16]. Traditionally, definitive radiotherapy for locally advanced NSCLC targets the primary disease and nodal metastases as well as the mediastinum and ipsilateral hilum whether or not there is clinical involvement of all nodal stations [6, 7, 9, 10, 11, 13, 17, 18, 22]. This technique is known as elective nodal irradiation (ENI). Potential dose–response has been reported, and an increased radiation dose has been believed to improve survival in NSCLC before RTOG 0617 [5, 26]. Involved field radiotherapy (IFRT) is a radiation treatment technique that minimizes the radiation dose to uninvolved areas [47]. For example, Figure 2 indicates the difference in planning target volume (PTV) between ENI and IFRT. IFRT allows radiation doses to be increased to the primary tumor and involves mediastinal lymph nodes. Thus, landmark clinical trials testing dose escalation adopted IFRT [27, 48, 49]. Although there are limited data directly comparing IFRT and ENI, the elective nodal failure rate after IFRT has been reported to be <10% in most reports [50, 51, 52, 53, 54, 55, 56]. Generally, EFRT can decrease the risk of severe toxicities, including acute esophagitis and pneumonitis, while showing no significant differences in elective nodal failure rate and survival outcomes in comparison with ENI [54, 55, 56]. Importantly, metastatic nodes should be defined with the guidance of PET images [46, 57]. Thereafter, CTV is generated by adding 5 to 10 mm to the gross tumor volume (GTV) of the primary tumor (typically 8 mm and 6 mm for adenocarcinoma and squamous carcinoma, respectively) and 3 mm for GTV of metastatic nodes of <20 mm [46, 58, 59].
Figure 2.
Differences in radiotherapy target selection in elective nodal irradiation and involved field radiotherapy. Squamous cell carcinoma in the upper lobe of the right lung with nodal metastases (cT3N2M0). Red, green, and blue indicates gross tumor volume (GTV), planning target volume (PTV) for elective nodal irradiation (ENI), and that for involved field radiotherapy (IFRT), respectively. The clinical target volume (CTV) for ENI including the upper mediastinum enlarges the size of the PTV.
4.2 Respiratory management in locally advanced NSCLC
An important challenge for lung cancer radiotherapy treatment is the management of physiological movements related to breathing. The lung tumors can move during breathing. Usually, to ensure adequate dose delivery to the tumor, an appropriate margin is added around the tumor. Four-dimensional computed tomography (4DCT) is a technique that allows to quantify the movement of the tumor with the use of respiratory reduction equipment such as an abdominal compression device. The internal target volume (ITV) is delineated on the 4DCT scan in order to account for tumor motion, and an additional margin is added to generate PTV. However, the target is large as it covers the entire tumor motion, especially in tumors in the lower lobe of the lung [60].
The breath-hold technique has been used to minimize the target volume, which must be irradiated with high-dose radiation and can help to reduce risk of radiation pneumonitis (Figure 3). In particular, the deep inspiration breath hold (DIBH) technique provides an advantage to a free-breathing treatment and could reduce the dosimetric parameters of normal organs such as the lung in dose-volume histograms [61]. DIBH gating has been clinically used in thoracic and upper abdominal radiotherapy [62]. In addition, it has recently been reported that compliance and reproducibility of DIBH was sufficiently high, with a reported compliant rate of 72% in a prospective clinical study [63]. DIBH has a high potential as a standard treatment in definitive radiotherapy for locally advanced NSCLC.
Figure 3.
Breath hold technique can minimize a target volume. Non-small cell lung cancer in the lower lobe of the left lung. Red, orange blue, and green indicate gross tumor volume (GTV), accumulated GTV on four-dimensional computed tomography (4DCT), planning target volume (PTV) using the breath-hold technique (exhale), and PTV, which was generated by accounting tumor motion in 4DCT, respectively. The breath-hold technique reduces the target volume.
4.3 Image-guided radiotherapy in locally advanced NSCLC
In recent years, advancements in image-guided radiotherapy (IGRT) technology have enabled more accurate positioning and precise radiotherapy. IGRT is an essential companion to IMRT and allows the treatment to account for daily changes in target anatomy, motion, and positioning. Megavoltage (MV) portal imaging had been conventionally used to correct the setup errors and limited to verification of bony anatomy. In recent years, the X-ray source for imaging has been evolving from MV imaging to kilovoltage (kV) imaging, and from two-dimensional to three- dimensional imaging. Modern IGRT is performed with either gantry mounted MV or kV cone beam computed tomography (CBCT) or room-mounted kV systems for tracking during treatment. IGRT allows for easier and improved accuracy leading more frequent positioning changes with leading to a therapeutic advantage. Kilburn et al. has reported that IGRT using daily CBCT improved locoregional tumor control than radiotherapy using weekly MV portal images [64].
Three-dimensional images in CBCT are used not only for positioning but also for the evaluation of the radiotherapy planning by dose calculation on the CBCT images. It has recently been reported that dose distribution and dose volume histogram were accurately calculated on CBCT images with a deformable imaging registration [65].
Further, acquired images from CBCT can be used for individualized treatment, called adaptive radiotherapy (ART). Since there are possibe changes of tumor and surround tissues during the treatment courses due to tumor shrinking and anatomical changes, it is necessary to modify the radiotherapy plan with accounting the appropriate margin, positioning, and tumor. CBCT provides significant three-dimensional information to evaluate if the patient would benefit from a re-scanning and re-planning. Indeed, ART can improve locoregional tumor control over radiotherapy without ART [66].
Daily IGRT with CBCT and ART has been reported to reduce toxicity and probably increase tumor response due to a better tumor localization and reduction of an interfraction target miss due to anatomical changes [64, 66, 67]. Further studies should be conducted in order to establish the optimal systemic replanning technique.
5. Future perspectives of definitive radiotherapy for locally advanced NSCLC
5.1 Failure pattern and potential salvage after definitive radiotherapy
Approximately 40% and 50% of locally advanced NSCLC patients experience locoregional and distant failures two years after the definitive chemoradiotherapy [27]. Consolidation ICI has been proven to reduce disease progression in both the intrathoracic and extrathoracic areas [32, 68]. Time to death or distant metastasis was longer, and the frequency of new lesions was lower with the use of durvalumab in comparison with placebo [32]. Notably, distant failure occurred in one or two lesions (66.6% in durvalumab arm) in a single organ (95.2% in durvalumab arm) at first progression in both arms of durvalumab and placebo with a median follow-up of 25.2 months [68]. Therefore, there seems to be a window of opportunity for treating these limited failures as a salvage, which might lead to a longer survival [69, 70, 71]. Cutting-edge radiotherapies, such as stereotactic radiotherapy and particle therapy, have the potential to be a prospective option as a salvage modality.
The results of the PACIFIC clinical trial have led to the design of several clinical trials combining radiotherapy with ICIs, including PACIFIC-2 study, where a chemoradiotherapy plus durvalumab arm is currently studied (NCT03519971). In addition, combining chemotherapy, radiotherapy, and ICIs with surgical resection is also under investigation in clinical trials (NCT03694236, NCT03237377, NCT04073745, NCT03348748).
There are oncological differences between pathological subtypes in NSCLC, as widely known in metastatic diseases [72]. Ito et al. showed that adenocarcinoma and squamous cell carcinoma tended to develop distant and locoregional failures, respectively, after chemoradiotherapy for locally advanced NSCLC [73]. In addition, non-squamous cell carcinoma tends to benefit more from adding durvalumab than squamous cell carcinoma, although there is a lack of direct comparison analysis [32]. The effects of histopathological and oncological differences in NSCLC on definitive chemoradiotherapy should be investigated with the aim of developing a precision treatment for locally advanced NSCLC.
5.2 Immune enhancement and preservation in radiotherapy
Recent developments in immunotherapy have started a new era in the treatment of various malignancies, including NSCLC [29, 30, 74]. Induction of the expression of immune checkpoint molecules such as PD-L1 results in the inhibition of T cell function and immune tolerance of tumors.
Radiation may cause immune activation through cytokine signaling and tumor antigen release [75, 76]. However, PD-L1 expression in tumors has been reported to be upregulated by radiation exposure in both pre-clinical and clinical settings and can suppress the immunogenic effect on tumors [75, 76, 77, 78]. ICIs block the immunosuppressive mechanisms of cancer cells and have a synergistic effect in combination with radiotherapy [75, 77]. The addition of durvalumab was proven to benefit disease control and survival after definitive chemoradiotherapy for locally advanced NSCLC [28, 31, 32]. The density of CD8+ tumor-infiltrating lymphocytes was significantly associated with favorable survival in locally advanced NSCLC patients undergoing chemoradiotherapy [79]. In their report, PD-L1 expression, which could be blocked by ICIs, was associated with inferior survival. In addition, radiation-induced lymphopenia has been reported to be associated with inferior survival [80, 81]. Therefore, radiotherapy will be modified to enhance the immune response to tumors. Hypofractionated regimens might have less immunosuppressive effects and are more appropriate than conventional fractionated regimens in terms of immune preservation [82, 83]. A clinical trial has been designed to test the addition of durvalumab to two schedules of radiotherapies of conventional and hypofractionated schedules (NCT03801902). Ongoing clinical trials in terms of definitive radiotherapy combined with ICIs are summarized in Table 2.
ClinicalTrials.gov identifier
Study design
Brief of treatment
NCT04432142
Phase 2
Immune changes after concurrent chemoradiation followed by durvalumab
NCT03589547
Phase 2
Durvalumab and consolidation SBRT following chemoradiation
NCT04092283
Phase 3
Durvalumab as concurrent and consolidative therapy or consolidative therapy alone
NCT03801902
Phase 1
Accelerated or conventionally fractionated radiotherapy combined with durvalumab
NCT03663166
Phase 1, 2
Chemoradiotherapy with ipilimumab followed by nivolumab
NCT04310020
Phase 2
Hypofractionated radiotherapy followed by atezolizumab
NCT03693300
Phase 2
Durvalumab following sequential chemotherapy and radiotherapy
NCT04249362
Phase 2
Durvalumab following radiotherapy (standard or hypofractionated bioequivalent dose)
NCT04392505
Phase 2
Investigating biomarkers related to chemoradiation followed by durvalumab
NCT04505267
Phase 1
Reirradiation with NBTXR3 for locoregional recurrence
Table 2.
Ongoing phase 1 to 3 clinical trials for locally advanced NSCLN in terms of definitive radiotherapy and immune therapy.
Searched for: radiotherapy, immune | Recruiting, Not yet recruiting Studies | Non-small Cell Lung Cancer Stage III at https://clinicaltrials.gov with excluding trials including surgery on Sep. 7, 2020.
PTV size can be associated with circulating blood, including the leukocytes [84]. Thus, IFRT is appropriate in terms of not only reducing the risk of pneumonitis but also preservation of the host immune system. Ladbury et al. have presented a predictive model of the estimated dose of radiation to immune cells, which was calculated using the radiation doses for heart, lung, body, and number of fractions, and was associated with cancer-specific outcomes [85]. Thereafter, sparing the host immune system will be discussed, and new optimizing theory for IMRT should be investigated in the future. Radio-immune therapy strategy is giving a new direction to radiotherapy and is warranted to explore future definitive radiotherapy for locally advanced NSCLC.
6. Conclusions
In this chapter, the historical improvement and the current recommendation of definitive radiotherapy for locally advanced NSCLC are described. The current standard treatment for locally advanced NSCLC is definitive radiotherapy, concurrently combined with chemotherapy, followed by anti-PD-L1 treatment. In order to improve outcomes and minimize radiation-induced toxicity, IMRT using an involved-field under modern management of respiration is a present recommendation in this chapter. An optimal combination of radiotherapy and immunotherapy should be warranted in a future investigation.
Acknowledgments
This work was supported by JSPS KAKENHI Grant Number JP20K08093.
\n',keywords:"lung cancer, radiotherapy, chemoradiotherapy, intensity modulated radiation therapy, dulvalumab",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/73359.pdf",chapterXML:"https://mts.intechopen.com/source/xml/73359.xml",downloadPdfUrl:"/chapter/pdf-download/73359",previewPdfUrl:"/chapter/pdf-preview/73359",totalDownloads:62,totalViews:0,totalCrossrefCites:0,dateSubmitted:"July 13th 2020",dateReviewed:"September 8th 2020",datePrePublished:"September 25th 2020",datePublished:null,dateFinished:null,readingETA:"0",abstract:"Lung cancer remains one of the most common cancers, and the mortality rate is still high. Radiotherapy plays an important role in radical treatment for locally advanced non-small cell lung cancer. Treatment outcomes in lung cancer have improved over the last few decades. Several treatment regimens have been shown to be effective and safe. Further, modern technological approaches of radiotherapy have been developed along with advanced imaging and immunotherapy in order to improve outcomes and minimize radiation-induced toxicity. This chapter summarizes the historical results of the key clinical studies that were conducted in the past with the focus on various regimens of chemoradiotherapy used. In addition, we discuss future perspectives of definitive radiotherapy for locally advanced non-small cell lung cancer.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/73359",risUrl:"/chapter/ris/73359",signatures:"Hiroshi Doi and Kozo Kuribayashi",book:{id:"10437",title:"Lung Cancer - Modern Multidisciplinary Management",subtitle:null,fullTitle:"Lung Cancer - Modern Multidisciplinary Management",slug:null,publishedDate:null,bookSignature:"Dr. Henry S. Park",coverURL:"//cdnintech.com/web/frontend/www/assets/cover.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:[{id:"96610",title:"Dr.",name:"Henry",middleName:"S.",surname:"Park",slug:"henry-park",fullName:"Henry Park"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. History of the development of definitive radiotherapy for locally advanced NSCLC",level:"1"},{id:"sec_3",title:"3. Utility of intensity-modulated radiotherapy, learning from RTOG 0617 and PACIFIC trials",level:"1"},{id:"sec_4",title:"4. Tips for using definitive radiotherapy for locally advanced NSCLC",level:"1"},{id:"sec_4_2",title:"4.1 Involved-field radiotherapy",level:"2"},{id:"sec_5_2",title:"4.2 Respiratory management in locally advanced NSCLC",level:"2"},{id:"sec_6_2",title:"4.3 Image-guided radiotherapy in locally advanced NSCLC",level:"2"},{id:"sec_8",title:"5. Future perspectives of definitive radiotherapy for locally advanced NSCLC",level:"1"},{id:"sec_8_2",title:"5.1 Failure pattern and potential salvage after definitive radiotherapy",level:"2"},{id:"sec_9_2",title:"5.2 Immune enhancement and preservation in radiotherapy",level:"2"},{id:"sec_11",title:"6. Conclusions",level:"1"},{id:"sec_12",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Walters S, Maringe C, Coleman MP, et al. Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004-2007. Thorax. 2013;68:551-564'},{id:"B2",body:'NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Non-Small Cell Lung Cancer Version 6. 2020 https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf [Accessed: 2020-Aug-01]'},{id:"B3",body:'Park K, Vansteenkiste J, Lee KH, Pentheroudakis G, Zhou C, Prabhash K, et al. 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Continuous, hyperfractionated, accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer: mature data from the randomised multicentre trial. CHART Steering committee. Radiotherapy and Oncology. 1999;52:137-148'},{id:"B19",body:'Nyman J, Friesland S, Hallqvist A, Seke M, Bergström S, Thaning L, et al. How to improve loco-regional control in stages IIIa-b NSCLC? Results of a three-armed randomized trial from the Swedish Lung Cancer Study Group. Lung Cancer. 2009;65:62-67'},{id:"B20",body:'Haslett K, Pöttgen C, Stuschke M, Faivre-Finn C. Hyperfractionated and accelerated radiotherapy in non-small cell lung cancer. J Thorac Dis. 2014;6:328-335'},{id:"B21",body:'Mauguen A, Le Pechoux C, Saunders MI, Schild SE, Turrisi AT, Baumann M, et al. Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis. 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Multinational Randomized Phase III Trial With or Without Consolidation Chemotherapy Using Docetaxel and Cisplatin After Concurrent Chemoradiation in Inoperable Stage III Non–Small-Cell Lung Cancer: KCSG-LU05-04. Journal of Clinical Oncology. 2015;33:2660-2666'},{id:"B25",body:'Tsujino K, Kurata T, Yamamoto S, Kawaguchi T, Kubo A, Isa S, et al. Is consolidation chemotherapy after concurrent chemo-radiotherapy beneficial for patients with locally advanced non-small-cell lung cancer? A pooled analysis of the literature. J Thorac Oncol. 2013;8:1181-1189'},{id:"B26",body:'Martel M. Estimation of tumor control probability model parameters from 3-D dose distributions of non-small cell lung cancer patients. Lung Cancer. 1999;24:31-37'},{id:"B27",body:'Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16:187-199'},{id:"B28",body:'Gray JE, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC. J Thorac Oncol. 2020;15:288-293'},{id:"B29",body:'Granier C, De Guillebon E, Blanc C, Roussel H, Badoual C, Colin E, et al. Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. ESMO Open. 2017;2:e000213'},{id:"B30",body:'Wagner G, Stollenwerk HK, Klerings I. Efficacy and safety of immune checkpoint inhibitors in patients with advanced non–small cell lung cancer (NSCLC): a systematic literature review. 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Alteration in tumoural PD-L1 expression and stromal CD8-positive tumour-infiltrating lymphocytes after concurrent chemo-radiotherapy for non-small cell lung cancer. Br J Cancer. 2019;121:490-496'},{id:"B79",body:'Tokito T, Azuma K, Kawahara A, Ishii H, Yamada K, Matsuo N, et al. Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy. Eur J Cancer. 2016;55:7-14'},{id:"B80",body:'Tang C, Liao Z, Gomez D, Levy L, Zhuang Y, Gebremichael RA, et al. Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer patient outcomes. Int J Radiat Oncol Biol Phys. 2014;89:1084-1091'},{id:"B81",body:'Wang W, Huang L, Jin J-Y, Jolly S, Zang Y, Wu H, et al. IDO Immune Status after Chemoradiation May Predict Survival in Lung Cancer Patients. Cancer Research. 2018;78:809-816'},{id:"B82",body:'Wang W, Huang L, Jin J-Y, Pi W, Ellsworth SG, Jolly S, et al. A Validation Study on IDO Immune Biomarkers for Survival Prediction in Non-Small Cell Lung Cancer: Radiation Dose Fractionation Effect in Early-Stage Disease. Clin Cancer Res. 2020;26:282-289'},{id:"B83",body:'Crocenzi T, Cottam B, Newell P, Wolf RF, Hansen PD, Hammill C, et al. A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma. Journal for ImmunoTherapy of Cancer. 2016;4:45'},{id:"B84",body:'Yovino S, Kleinberg L, Grossman SA, Narayanan M, Ford E. The etiology of treatment-related lymphopenia in patients with malignant gliomas: modeling radiation dose to circulating lymphocytes explains clinical observations and suggests methods of modifying the impact of radiation on immune cells. Cancer Invest. 2013;31:140-144'},{id:"B85",body:'Ladbury CJ, Rusthoven CG, Camidge DR, Kavanagh BD, Nath SK. Impact of Radiation Dose to the Host Immune System on Tumor Control and Survival for Stage III Non-Small Cell Lung Cancer Treate d with Definitive Radiation Therapy. International Journal of Radiation Oncology*Biology*Physics. 2019;105:346-355'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Hiroshi Doi",address:"h-doi@med.kindai.ac.jp",affiliation:'
Department of Radiation Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Japan
'}],corrections:null},book:{id:"10437",title:"Lung Cancer - Modern Multidisciplinary Management",subtitle:null,fullTitle:"Lung Cancer - Modern Multidisciplinary Management",slug:null,publishedDate:null,bookSignature:"Dr. Henry S. Park",coverURL:"//cdnintech.com/web/frontend/www/assets/cover.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:[{id:"96610",title:"Dr.",name:"Henry",middleName:"S.",surname:"Park",slug:"henry-park",fullName:"Henry Park"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"199850",title:"Dr.",name:"Lin",middleName:null,surname:"Jing",email:"jinglin_426@163.com",fullName:"Lin Jing",slug:"lin-jing",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"2",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:{name:"Southwest Jiaotong University",institutionURL:null,country:{name:"China"}}},booksEdited:[],chaptersAuthored:[{title:"Wheel-Rail Impact by a Wheel Flat",slug:"wheel-rail-impact-by-a-wheel-flat",abstract:"The finite element method (FEM)-based wheel-rail rolling contact model with a fresh wheel flat was built to investigate the wheel-rail impact responses, where a comprehensive dynamic explicit algorithm was employed. Two basic dynamic effects (i.e., inertia effect and strain-rate effect) and temperature effect during the wheel-rail sliding process were considered. Influences of train speed, flat length and axle load on the wheel-rail impact responses were discussed in terms of wheel-rail impact force, von Mises equivalent stress, equivalent plastic strain and XY shear stress. Simulation results demonstrate that the FEM-based wheel-rail rolling contact model can well describe the strong nonlinearities in geometry, contact and material. The strain rate effect contributes to elevate the maximum von Mises equivalent stress and restrain the plastic deformation. The initial thermal stress can decrease the maximum von Mises equivalent stresses and maximum XY shear stresses, but can aggravate the plastic deformation. Furthermore, the flat-induced wheel-rail impact force, von Mises equivalent stress, equivalent plastic strain and XY shear stress are revealed to be sensitive to train speed, flat length and axle load.",signatures:"Lin Jing",authors:[{id:"199850",title:"Dr.",name:"Lin",surname:"Jing",fullName:"Lin Jing",slug:"lin-jing",email:"jinglin_426@163.com"}],book:{title:"Modern Railway Engineering",slug:"modern-railway-engineering",productType:{id:"1",title:"Edited Volume"}}},{title:"Single-Curvature Sandwich Panels with Aluminum Foam Cores under Impulsive Loading",slug:"single-curvature-sandwich-panels-with-aluminum-foam-cores-under-impulsive-loading",abstract:"Single-curvature sandwich panels combine the advantages of the shell and sandwich structure and are therefore envisaged to possess good potential to resist blast and shock or impact loads. This study presents a comprehensive report on the dynamic response and shock resistance of single-curvature sandwich panels, comprising two aluminum alloy face-sheets and an aluminum foam core, subjected to air-blast loading, in terms of the experimental investigation and numerical simulation. The deformation modes, shock resistance capability, and energy absorption performance are studied, and the influences of specimen curvature, blast impulse, and geometrical configuration are discussed. Results indicate that the deformation/failure, deflection response, and energy absorption of curved sandwich panels are sensitive to the loading intensity and geometric configuration. These results are significant to guide the engineering applications of sandwich structures with metallic foam cores subjected to air-blast loading.",signatures:"Lin Jing, Zhihua Wang and Longmao Zhao",authors:[{id:"199850",title:"Dr.",name:"Lin",surname:"Jing",fullName:"Lin Jing",slug:"lin-jing",email:"jinglin_426@163.com"},{id:"202005",title:"Prof.",name:"Zhihua",surname:"Wang",fullName:"Zhihua Wang",slug:"zhihua-wang",email:"wangzh@tyut.edu.cn"},{id:"202006",title:"Prof.",name:"Longmao",surname:"Zhao",fullName:"Longmao Zhao",slug:"longmao-zhao",email:"zhaolongmao@tyut.edu.cn"}],book:{title:"Contact and Fracture Mechanics",slug:"contact-and-fracture-mechanics",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"140822",title:"Dr.",name:"Fouzia",surname:"Elbahhar",slug:"fouzia-elbahhar",fullName:"Fouzia Elbahhar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/140822/images/3817_n.png",biography:"Dr. Fouzia Elbahhar Boukour was born in 1975. She received the M.S and Ph.D degrees form the University of Valenciennes (France) in 2000 and 2004, respectively. She is actually employed as researcher at IFSTTAR/LEOST, Villeneuve d’Ascq, France. Fouzia Boukour is author or coauthor of more than 50 research papers, including journal articles, book chapters and conference proceedings. She participates at many national and European projects dedicated to transport applications. She serves also as a reviewer for several journals and international Conference. She is involved in signal processing especially Ultra wide band technology. Her major research interests are land transportation like Communication Vehicle to Vehicle and vehicle to Infrastructure, localisation.",institutionString:null,institution:{name:"French Institute of Science and Technology for Transport, Spatial Planning, Development and Networks",institutionURL:null,country:{name:"France"}}},{id:"144884",title:"Dr.",name:"Muzaffer",surname:"Metin",slug:"muzaffer-metin",fullName:"Muzaffer Metin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/144884/images/5943_n.jpg",biography:"Muzaffer Metin spent 3 years in industrial research before he took up an academic position at Yildiz Technical University, where he is currently Assist.Professor of Machine Theory, System Dynamics and Control Department. He is also a part-time professor in the Istanbul Aydin University. His research is concerned with a variety of practical applications of railway system dynamics and advanced control of vibrations. Specific projects are concerned with vibration control of railway superstructures and active railway vehicle suspensions. His projects are characterized by strong industrial collaboration, having worked with companies such as Metro Istanbul, Tüvasaş, Tüdemsaş, and TCDD-Datem.\nHe undertook a PhD in the dynamics of light railway vehicles sponsored by the Metro Istanbul AŞ in Istanbul. For 4 years, he gave consultancy on dynamic analysis and vibration and acoustic tests of rail vehicles at Istanbul Tram project to the Metro Istanbul R & D team. He spent 12 years as Researcher and Lecturer at Yildiz Technical University teaching and carrying out research into the railway system dynamics and vibration insulation where, in 2016, he set up the Railway System Investigation Laboratory which provided expert advice and solutions for the railway industry.",institutionString:null,institution:null},{id:"171013",title:"Dr.",name:"Cesar",surname:"Briso",slug:"cesar-briso",fullName:"Cesar Briso",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"206138",title:"Dr.",name:"Ade",surname:"Ogunsola",slug:"ade-ogunsola",fullName:"Ade Ogunsola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Parsons (United States)",institutionURL:null,country:{name:"United States of America"}}},{id:"207255",title:"Dr.",name:"Davod",surname:"Poreh",slug:"davod-poreh",fullName:"Davod Poreh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/207255/images/system/207255.png",biography:"Dr. Davod Poreh Ph.D. is a member of DIETI Department of Electrical Engineering in University of Naples Federico II. He has been working in radar satellite/airborne remote sensing, laser remote sensing, and passive satellite remote sensing in many European countries including Germany and Italy, consequently studying and producing many radar interferograms, persistent scatterers, polarimetiric data sets, airborne/sea laser data, topographic data, etc. His main research interests are in the field of electromagnetic, microwave and passive remote sensing, image processing (optical and SAR), radar, polarimetric SAR, interferometreic SAR, sensor design, antenna, polarimetric based radar simulations, InSAR time series (persistent scatterers interferometry, and SBAS), ground penetrating radar, seismic, gravity, electromagnetic geophysics, information retrieval for land, oceanic, and urban area, EO programming, and GIS.",institutionString:"University of Naples Federico II",institution:{name:"University of Naples Federico II",institutionURL:null,country:{name:"Italy"}}},{id:"216915",title:"Dr.",name:"Juan",surname:"Moreno Garcia-Loygorri",slug:"juan-moreno-garcia-loygorri",fullName:"Juan Moreno Garcia-Loygorri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"216916",title:"Dr.",name:"Lei",surname:"Zhang",slug:"lei-zhang",fullName:"Lei Zhang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Shanghai Institute of Microsystem and Information Technology",institutionURL:null,country:{name:"China"}}},{id:"222685",title:"MSc.",name:"Arif",surname:"Ulu",slug:"arif-ulu",fullName:"Arif Ulu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"222686",title:"MSc.",name:"Mahmut",surname:"Paksoy",slug:"mahmut-paksoy",fullName:"Mahmut Paksoy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"222687",title:"M.Sc.",name:"Murat Emre",surname:"Yucel",slug:"murat-emre-yucel",fullName:"Murat Emre Yucel",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"our-story",title:"Our story",intro:"
The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.
",metaTitle:"Our story",metaDescription:"The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.",metaKeywords:null,canonicalURL:"/page/our-story",contentRaw:'[{"type":"htmlEditorComponent","content":"
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\\n\\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\\n\\n
The IntechOpen timeline
\\n\\n
2004
\\n\\n
\\n\\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\\n\\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\\n
\\n\\n
2005
\\n\\n
\\n\\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\\n
\\n\\n
2006
\\n\\n
\\n\\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\\n
\\n\\n
2008
\\n\\n
\\n\\t
Downloads milestone: 200,000 downloads reached
\\n
\\n\\n
2009
\\n\\n
\\n\\t
Publishing milestone: the first 100 Open Access STM books are published
\\n
\\n\\n
2010
\\n\\n
\\n\\t
Downloads milestone: one million downloads reached
\\n\\t
IntechOpen expands its book publishing into a new field: medicine.
\\n
\\n\\n
2011
\\n\\n
\\n\\t
Publishing milestone: More than five million downloads reached
\\n\\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\\n\\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\\n\\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\\n
\\n\\n
2012
\\n\\n
\\n\\t
Publishing milestone: 10 million downloads reached
\\n\\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\\n
\\n\\n
2013
\\n\\n
\\n\\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\\n
\\n\\n
2014
\\n\\n
\\n\\t
IntechOpen turns 10, with more than 30 million downloads to date.
\\n\\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\\n
\\n\\n
2015
\\n\\n
\\n\\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\\n\\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\\n\\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\\n\\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\\n
\\n\\n
2016
\\n\\n
\\n\\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\\n
\\n\\n
2017
\\n\\n
\\n\\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\\n\\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\n\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\n\n
The IntechOpen timeline
\n\n
2004
\n\n
\n\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\n\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\n
\n\n
2005
\n\n
\n\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\n
\n\n
2006
\n\n
\n\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\n
\n\n
2008
\n\n
\n\t
Downloads milestone: 200,000 downloads reached
\n
\n\n
2009
\n\n
\n\t
Publishing milestone: the first 100 Open Access STM books are published
\n
\n\n
2010
\n\n
\n\t
Downloads milestone: one million downloads reached
\n\t
IntechOpen expands its book publishing into a new field: medicine.
\n
\n\n
2011
\n\n
\n\t
Publishing milestone: More than five million downloads reached
\n\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\n\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\n\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\n
\n\n
2012
\n\n
\n\t
Publishing milestone: 10 million downloads reached
\n\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\n
\n\n
2013
\n\n
\n\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\n
\n\n
2014
\n\n
\n\t
IntechOpen turns 10, with more than 30 million downloads to date.
\n\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\n
\n\n
2015
\n\n
\n\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\n\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\n\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\n\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\n
\n\n
2016
\n\n
\n\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\n
\n\n
2017
\n\n
\n\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\n\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
\n
\n"}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). 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