Impact of COVID-19 on teaching and learning by region.
\r\n\t
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He has carried out a great deal of research and technical survey work, and has performed several studies in the above-mentioned areas. He has edited many international books and is an active member of many worldwide architectural associations. 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Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"73505",title:"Is University Education Limited by Globalization and Technology in Developing Countries? An Observation Done during Pandemic",doi:"10.5772/intechopen.94044",slug:"is-university-education-limited-by-globalization-and-technology-in-developing-countries-an-observati",body:'Globalization interconnects the world, making it a small village through time and space where technology is the main and important facilitator of this interconnectivity [1]. This process is marked by speedy, free movement of people, services, capital, goods, ideas and knowledge across borders [2]. A question becomes, how practical is the term globalization in describing educational systems of developing countries? Through technology, globalization facilitates access and sharing of most recent knowledge across the globe. Online classes, scholarly references, and academic communications in higher education and universities provide proof that education is pinned down by both globalization and technology.
During times of minimum physical contacts, like what happened recently due to COVID-19 pandemic; one might expect the benefits of globalization and technology to outshine. In educational systems, this would mean continuation of studies and communication among those involved. Unfortunately, in some developing counties benefits of globalization and technology to university educations had their limitations during the times of pandemic. Some universities had to seize classes completely simply because technology was limited in its application.
Authors of this chapter argue that: the terms globalization and technology are used disproportionately and unfairly when it comes to university education within developing counties. The two terms tend to mask the reality of the limitations they cause. Maybe, if developing countries had accepted that they are not globalized enough as assumed and masked by the term ‘globalization’; and that the available technologies are not advanced enough, they would find ways to continue educating during the times of pandemic. Instead, for developing countries to rely on globalized technology has proven limited during this challenging time.
Globalization or global links are mentioned to have started to form since the early 19th century where rapid interconnectedness across the globe was witnessed [1]. Since the 90’s the term globalization emphasizes on interconnection among nations across the continents, and described as: not limiting investments, production and innovations within one nation’s borders [3]. Authors of this chapter think that a nation must reach a certain level of development technologically before entering the state of being globalized. Such development at national level should not be judged as a complete hindrance in globalization of both education and career rather indicates the need to amend the national approaches to address the population demand of the developing countries preferably in the indigenous manner [4]. Authors of this chapter observed that developing counties are said to be ‘globalized’ and ‘technologically connected with other nations’ but found to be technologically limited within a country. A good example is the observation done at the university educational system during the pandemic. Authors of this chapter observed that university education is limited by the unevenness of the term globalization intersected by the irregularity of technology. The use of the terms when elaborating university education creates assumptions that there is an equal distribution of their benefits.
The term globalization makes authors of this chapter think of importance of nationalization and rationalization [4]. In order to deliver higher education successfully, maybe a country should be termed as ‘nationalized’ first before being globalized. This way we can use the term globalization in the assurance that connection is successful within a nation before spreading global. As a university lecturer, this will mean that I should be able to communicate with my students within my country same way I can use technology to connect with other academicians in foreign countries. To our opinion, when the system of education is said to be modernized and globalized, then its availability and accessibility should not be in a limited context both nationally and globally.
Globalization can strengthen or weaken educational systems in a particular nation: a good example of educational policies. In coping with globalization, developing counties must develop their educational policies not only to serve national needs, but also to be integrated to accommodate the global context with positive impacts. Al’Abri who assessed influence of globalization on educational policy at Oman, argues that; educational policies within developing countries in the context of globalization are strongly influenced by the role of international organizations when compared similar influence to developed ones. Accordingly, education policy is no longer determined by actors within the nation state alone, but through various complex processes occurring globally [2]. International organizations such as the UN, the World Bank, and Organization for Economic Co-operation and Development (OECD) are claimed to have more powerful impact on education policy of low income and developing countries through their practices, programs and policies such as the UN’s Millennium Development Goals, Education for All, and others [5]. Accordingly, education policy in developing countries is globalized.
Educational policy terrain is confirmed to be reformed and redesigned by globalization [2, 6]. Authors at [2, 6] argue that the process of globalization has deeply shifted and changed the ways in which education policies are developed, implemented and evaluated.
Technology can be defined as the use of scientific knowledge for practical purposes or any other life applications, whether in industries or in our everyday lives [7]. Subsequently, we are using technology whenever we use our scientific knowledge to achieve some specific purposes. Generally, Technology can be anything from the discovery of simple things up to complicate ones [8]. Since technology can be so simple or so complex, different colleges/universities have been operating using different technologies in different aspects.
Colleges and universities have generally been quick to adopt new technologies, regularly even before their educational value has been confirmed. Throughout history, higher education institutions have investigated with technological advances as diverse as the blackboard and the personal computer [9]. The use of computers, internet and telecommunications are the major technologies reforming higher education. The use of electronic mail, fax machines, the World Wide Web, CDROMs, and commercially developed meeting software apps are altering the daily operations and expanding the duties of colleges and universities. Some technologies such as the use of slides, projectors, and other audio -visual skills have now become permanent parts of higher learning institutions. These technologies are being used in different matters like teaching and communication [10]. This has been of great importance in different college/universities where the traditional teaching and learning process has been revolutionized.
Technology has been able to eliminate the barriers to education imposed by space and time and dramatically expand access to lifelong learning. Students no longer have to meet in the same place at the same time to learn together from instructors, instead, they can use technology to access different sessions, materials and academic meetings/appointments. We can now say that modern technology has transformed the concept of higher learning institutions that is no longer necessary for a college/university to have a physical place/building with classrooms or lecturing theaters but it can use technology to reach students [11]. Through sophisticated communication technologies; higher learning institutions are no longer restricted to have face to face communications between staff and students. They can now communicate via technologies from different geographical locations if and only when all required resources are in place. Technology can also make education a much more interactive and collaborative process to both students and stuff. The use of electrical mails, course-based websites, and computer-based chat rooms are some of the technology-enabled resources that facilitate communication and teamwork among students and their instructors.
Despite of all technology’s promise, its incorporation in some of higher learning institutions in developing countries has not been easy and successfully due to some difficulties including infrastructural settings [12]. Many barriers to technology-based innovations and investment costs have been limiting the total exposure of technological advances for stuff and students [9, 13]. In East-African settings with an example in Tanzania, most of academic institutions are so confined to classroom - centered lecture that make many instructors reluctant to adopt alternative instructional strategies using the computer or telecommunication devices [14].
Technology has also been found of disadvantages in university education settings where it has also brought a number of cold aspects. Among the disadvantages of technology are; many instructional positions have been obsolete, professors and instructors’ control of the curriculum has been lost, cheating on academic matters has been so easier to students, the importance of attending lectures has been ignored, the role of some instructors/mentors has been replaced by technologies and also technology has facilitated laziness for university students [15]. Together with this, the cost of many technological applications also prohibits their easy adoption at many resource-limited institutions.
In response to the coronavirus outbreak, many African governments took the decision to close all schools and higher learning institutions to contain the disease. Consequently, all higher learning institutions had to rethink the approach to become more digitally led and shifted to online platforms [16, 17]. The manifestation of coronavirus pandemic exposed the unpreparedness of many higher learning institutions in Africa to shift to online. The pandemic incidence caused many African governments to temporarily close all educational institutions and other places that gather people in order to contain the spread of COVID-19 in their respective countries. The closures of schools and universities is said to have impacted over 70% of the world’s population. The management of higher learning institutions in Africa have now understood the importance of encouraging students to embrace change in learning and teaching as well as to prepare themselves for any forthcoming events and other troubles that might become part of their lives [16].
The situation of higher education in the COVID-19 era has been an excellent lesson for higher education institutions in Africa to rethink what to consider in planning for future curriculum including steps to be taken towards adopting a blended learning approach in education to improve access and equity. During COVID-19 pandemic, several universities across Africa, such as Egypt, Ghana, South Africa, and Rwanda shifted some of their programmes to online platforms and partnered with Telco’s to zero-rate these platforms [13, 16]. These few universities in some instances made data packages and laptops available to some of their students’ access which was difficult to other African universities due to some geographical and technical challenges.
Nevertheless, even with all the efforts of some universities in Africa to ensure smooth teaching and learning via online platforms, limitation of globalization and technology still affect African university that hinder students from accessing their studies in case of any emergency like pandemic issues. According to UNESCO, 89% of students in sub-Saharan Africa do not have access to household computers and 82% lack internet access and thus even though there will be online classes still they cannot cater for all students in Africa [17].
During this pandemic, many strategies made by universities to make studies continue were observed. Some researchers like Kari Mugo, Naliaka Odera and Maina Wachira did a survey to know the impact of COVID-19 on Africa’s higher education and research sectors. On their survey, they found out that While 83% of respondents reported experiencing disturbance on their ongoing learning, only 39% said they were enrolled in institutions offering e-learning options. Only 17% of West African respondents reported being at institutions with e-learning options, compared to 43% of East African and 41% of respondents in Southern Africa. The survey added that even the research activities were affected whereby, 73% reported a suspension of their lab or field research activities as a result of the COVID-19 crisis. These results of the survey alert us to a broken system that has been worsened by a global pandemic. The researchers pointed out that, even if there were institutions offering e-learning, the trend across the continent was not homogeneous. They also found differences in accessing to e-learning based on a respondent’s gender, age and exposure to technological issues [18].
The impact of COVID-19 pandemic was not similar worldwide; different continents were affected differently. African regions were mostly affected by suspending teaching sessions and some teaching were mostly canceled in Africa compared to other continents surveyed. Results are summarized in Table 1.
Continents | Not affected | Classroom teaching replaced by distance teaching and learning | Teaching suspended but the institutions developed solutions | Teaching canceled |
---|---|---|---|---|
3% | 29% | 43% | 24% | |
3% | 72% | 22% | 3% | |
1% | 60% | 36% | 3% | |
Almost zero | 85% | 12% | 3% |
Impact of COVID-19 on teaching and learning by region.
It is through education that nations are termed as developed. An educated nation, using technology and interconnected with other nations is termed as developed. Education does not only speed up development processes, but also make development more linked to people’s needs. Development goals in most developing countries have been changed, related to and influenced considerably by globalization processes. Various authors conclude that education is a necessary component of development in responding to globalization and in achieving economic growth and social development. Education equips people with the new knowledge and skills needed for the acceptance and adoption of globalization [5, 19].
Technological innovations, creativity and output are all contained within an education system. In developing countries, both education and technology correlated together are looking for to provide solutions to both economic and social challenges [20, 21]. Therefore, education becomes crucial to developing countries as a means of creating channeled-opportunities for these countries to engage and integrate with the global economy and development. Education and technological level enable assessment of developing counties in the level of globalization. Clearly one country is termed as globalized based on the quality of education and technology available in that country. Therefore education becomes the core center that holds technology and globalization all together.
The observation was done mainly to university education in East Africa during the time of pandemic. Existence of pandemic forced both students and academicians to stay at home; technology was expected to facilitate the continuation of university education. After all it is a university education we are talking about where terms technology and globalization are highly applicable. Technology in university is used in all aspects of teaching (ICT, internet, modern lab equipment). Globalization is applicable under a notion that in order for a university to be permitted to offer higher education, there must be linkages, flow and continuous exchange of current knowledge and expertise between the universities across countries and sometimes continents. But should not these two terms globalization and technology enable university education to continue during the emergency time of pandemic? One might expect that to be the case. But in most developing countries their limitations were caused by inapplicability.
In Tanzanian universities for example; classes had to be frozen completely during the peak of pandemic. Students went home with minimum educational communication with their academic supervisors. Shouldn’t globalization (connection of the world) and technology (especially ICT) be helpful during this time? Had the globalized technology not being limited by evenness in accessibility, university studies during the pandemic would continue. We cannot deny or dare to overlook the importance and advantages of globalization and technology in the university education. We appreciate the two when we are able to access online classes with visual contact communications from other developed countries. However, to proudly apply the intersection of the two terms, continuity must be maintained during the emergency times of minimum contact.
It is through globalization that education has become a matter of international relation and concern. Technology has been able to facilitate this. But should the terms globalization and technology been used evenly to both developing and developed countries? The authors of this chapter argue that they should not. The evidence behind their arguments is because of what was witnessed on university education in developing countries during the time of pandemic. Even though we appreciate the benefits of the terms as applied to part of educational systems within developing counties, the unevenness usage of the terms create the assumptions that mask the reality of their limitations to university education.
Therefore the lesson learnt during pandemic serves as a call for all higher education institutions in developing countries to rethink and modify their curricular so as to suit a blended learning approach. To ensure equal access of globalized techniques and technologies in higher education institutions, authors recommend investment to improve resources and infrastructures within developing countries.
Authors of this chapter would like to acknowledge their families and Sokoine University of Agriculture for resources and moral support during the writing of this chapter.
“The authors declare no conflict of interest.”
Pancreatic cancer is the 13th most common malignancy worldwide, which was diagnosed in approximately 338,000 people in 2012. Pancreatic cancer is a very aggressive form of malignancy resulting in the seventh leading cause of cancer deaths worldwide, over 331,000 deaths in 2012 alone. The worldwide incidence of new pancreatic cancers was 4.9 in 100,000 persons with an associated mortality rate of approximately 4%. The incidence and deaths of pancreatic cancer is higher in developed countries, 188,000 and 184,000 persons as compared to less developed regions, 150,000 and 146,000 persons [1].
\nSpecifically looking at the USA, pancreatic cancer is the eighth most common type of malignancy and the fourth leading cause of cancer deaths. There are estimated 55,440 new cases of pancreatic cancer that will be diagnosed in the USA in 2018 and result in estimated 44,330 deaths. Incidence rate of pancreatic cancer has increased 1% per year from 2005 to 2014 [2].
\nMost pancreatic cancers develop from the pancreatic exocrine tissue (94%), such as invasive ductal adenocarcinoma, while the remaining 6% of tumors stem from the hormone-producing islet cells, such as insulinomas, gastrinomas, and other pancreatic neuroendocrine tumors (pNETs). Those pNets will typically occur in younger patients with a better overall prognosis. The focus of this chapter will be on invasive pancreatic ductal adenocarcinoma [2].
\nThe overall pancreatic cancer mortality rate has shown only slight improvement over the past 35 years. In 1975, pancreatic cancer mortality rate was observed at 3.1%, and in 2000, it increased to 5.2%. The largest incremental improvement in pancreatic cancer survival has occurred over the past 10 years (2008–2104), with the all stage 5 year survival between 8 and 8.5% [2, 3, 4].
\nFor the small percentage of patients with early-stage localized pancreatic cancer (10%), the 5-year survival is between 32 and 34.3%. Once regional lymph node involvement has developed, the 5 year survival decreases to 11.5–12%. Unfortunately, most pancreatic cancer patients (52%) are diagnosed with distant metastatic disease, and that 5-year survival is only 3% [2, 3].
\nAt this point in the time, the cause of pancreatic cancer is still unknown. Increasing age is a significant risk factor for developing pancreatic cancer. The median age of diagnosis of pancreatic cancer in both sexes is at 70 years old. In addition, men have an increased incidence of developing pancreatic cancer as compared to women, 14.4 vs. 11.2 per 100,000 persons across all race and ethnicity [1, 2, 3].
\nThere have been several risk factors to develop pancreatic cancer associated with race/ethnicity, environmental, dietary, medical, and genetic exposures identified (Table 1). Race is also another significant risk factor. African-Americans have the highest incidence (9.9 per 100,000 persons) and mortality (9.4 per 100,000 persons) of pancreatic cancer as compared to non-African-Americans [4]. In addition, Jews of Ashkenazi heritage also have an increased incidence of pancreatic cancer. The age standardized incidence rate of pancreatic cancer for Israeli Jews (7.2 per 100,000 males and 5.7 per 100,000 females) exceeds the incidence of Israeli non-Jews (4.0 per 100,000 males and 2.9 per 100,000 females) [5].
\nRisk factors for developing pancreatic cancer.
There are also several hereditary conditions associated with increased risk for pancreatic cancer (Table 2). While persons with these genetic syndromes are at increased risk for pancreatic cancer, they only account for 5% of all pancreatic diagnoses. Familial cases of pancreatic cancer are at increased incidence to develop secondary primary cancers as compared to non-familial-based cancers. Of those listed, Peutz-Jeghers and hereditary pancreatitis syndromes have the highest risk of developing pancreatic cancer [6, 7, 8, 9, 10, 11, 12].
\nGenetic syndromes with increased risk of pancreatic cancer.
Tobacco use is the most well-established modifiable risk factor for developing pancreatic cancer and accounts for up to 30% of all pancreatic cancer cases. There is at least a twofold increase in risk for developing pancreatic cancer in cigarette smoker than a non-smoker. The risk also increases with an increase in the number of cigarettes and duration of smoking. It may take up to 20 years after cessation of cigarette smoking for one’s risk of pancreatic cancer to be equal to take of a non-smoker [13].
\nThe current standard in pancreatic cancer staging is by use of a 64-slice multidetector computed tomography (CT). Specific CT pancreatic protocols can accurately stage the cancer and assess for resectability. These protocols include both the use of low-density oral contrast and nonionic iodinated contrast and scanned 30–45 seconds then again 60 seconds after injection to capture both arterial and venous phases. The arterial phase will allow for good visualization of the celiac axis, common hepatic artery, superior mesenteric artery, and gastroduodenal artery. The venous phase will show enhanced visualization of the portal vein, superior mesenteric vein, splenic vein, pancreatic parenchyma, and the liver to assess for metastatic disease [14, 15].
\nOnly 20% of patients who present with pancreatic cancer can undergo surgical resection since most patients present with either unresectable or metastatic disease. The only chance for a curative treatment is with the inclusion of successful surgical removal of the cancer. To determine the patient’s eligibility for pancreatic resection, an experienced pancreatic surgeon is required to review the dedicated pancreatic cross-sectional imaging. The relationship of the tumor to the major intra-abdominal vessels determines the resectability of the pancreatic cancer. Decisions regarding diagnostic and management and resectability should involve multidisciplinary consultation at high-volume center, at least 15–20 pancreatic resections per year [14].
\nIn 2006, the National Comprehensive Cancer Network (NCCN) criteria initially defined pancreatic cancers resectability status into three classifications: resectable, borderline resectable, and unresectable. Since that time, there have been several varying definitions of tumor resectability that have evolved over the past decade. Several international surgical societies such as the American Hepato-Pancreatico-Biliary Association (AHPBA), Society of Surgical Oncology (SSO), Society for Surgery of the Alimentary Tract (SSAT), and International Association of Pancreatology (IAP) have issued consensus statements on the definition and criteria of resectability and borderline resectable pancreatic cancers as illustrated in Table 3 [14, 15, 16].
\nDefinitions and criteria of resectable, borderline resectable and unresectable pancreatic cancer.
For a tumor to be considered resectable, it must not be in contact with the portal vein (PV) or superior mesenteric vein (SMV) per AHPBA/SSO/SSAT and IAP or less than 180° of contact with SMV/PV by NCCN criteria. By meeting these criteria, the surgeon believes there is a high likelihood of removing the cancer without leaving behind any residual tumor (R0 resection). When pancreatic cancers are classified as borderline resectable based on the vascular involvement, it means that there is a higher likelihood of having residual microscopic disease (R1 resection) if one was to proceed with upfront surgery. Borderline resectable means just that it is not quite resectable but not completely unresectable either. The criteria are less than 180° of arterial involvement of the superior mesenteric artery (SMA) or common hepatic artery (CHA) of celiac axis (CA). It also means there can be greater than 180° of involvement of SMV or even complete encasement of SMV or PV but still suitable for resection vascular reconstruction. Unresectable disease has greater than 180° of arterial involvement of SMA, CHA, or CA or non-reconstructable vein involvement including the first jejunal branch [14, 15, 16].
\nThe best outcomes come from margin negative surgical resection with no residual microscopic disease (R0). There is current debate at the true definition of R1 resection as either no microscopic tumor cells at the resection margin or if tumor cells are less than 1 mm from the resection margin. It has been found that the 5-year survival rate has been improved in patients with greater than 1 mm of clearance as compared to those with less than 1 mm. Margins with 0 mm, less than 1 mm, or greater than 1 mm had 5-year survival rates at 16.3, 12.4, and 27.6%, respectively [17]. There is no benefit to performing a surgical resection if gross tumor (R2 resection) will be the result as the prognosis is similar to patients with non-operative management [18].
\nPancreatic surgery should involve high-volume surgeons with the expertise in pancreatic resection. Decisions regarding the management of pancreatic cancer patients require a multidisciplinary team. The location of the tumor and extent of disease will dictate the surgical approaches. Pancreatic head and uncinate tumors require pancreaticoduodenectomy (Whipple procedure) with reconstruction of the pancreas, bile duct, and stomach. If possible, the aim is to preserve the pylorus to limit bile acid reflux and gastric emptying. Tumors that exist in the body and tail of the pancreas will typically require a left-sided surgical resection, distal pancreatectomy, and splenectomy. Borderline resectable and locally advanced cancers may also require venous and/or arterial reconstruction at the time of surgical resection of the pancreatic cancer.
\nIn patients with pancreatic cancer, the overall survival has improved due to systemic chemotherapy and combination therapies. It is still standard treatment to perform upfront surgical resection for resectable pancreatic cancer followed by adjuvant chemotherapy. However, there has been a shift toward upfront neoadjuvant chemotherapy in order to select out patients with latent metastatic disease or to downstage borderline and locally advanced cancers.
\nThe ESPAC-1 (European Study Group for Pancreatic Cancer) showed that there was improvement in overall survival using surgery plus adjuvant 5-fluorouracil (5-FU) plus folinic acid (FA). This three-tracked trial compared patients treated with chemotherapy alone, surgical resection alone, or chemotherapy plus radiation therapy. The highest 5-year survival was seen in the chemotherapy arm 21% as compared to surgery alone 8% and chemoradiation 11%. This revealed the only significant survival benefit was with adjuvant chemotherapy [19].
\nThe Charite Onkologie study (CONKO-001) from 2007 compared adjuvant gemcitabine therapy to observation in patients undergoing surgical resection of pancreatic cancer. In the treatment arm, patients received 6 cycles of adjuvant gemcitabine. Patients treated with adjuvant gemcitabine vs. surgery alone had statistically significant increased median overall survival of 22.8 months and 5-year survival of 21% compared to 20.2 months and 5-year survival of 9%. Gemcitabine also significantly delayed the development of recurrent disease as compared to observation alone [20].
\nThe ESPAC-3 was a large randomized controlled trial which compared adjuvant 5-FU plus leucovorin or gemcitabine in patients who underwent RO or R1 resection of pancreatic cancer. This was initially a three-arm study comparing 5-FU plus leucovorin, gemcitabine, and observation; however, once the results of the ESPAC-1 were available, the observation arm was closed. Results of ESPAC-1, ESPAC-1 plus, and ESPAC-3 in subset analysis of 5-FU/FA vs. observation confirmed that adjuvant 5-FU/FA had superior overall survival as compared to observation after surgical resection. The 5 year survival for 5-FU/FA was 24% compared to observation which was 14% [21].
\nESPAC-3 has enrolled 1088 patients and they were followed for over 6.5 years. Median survival for gemcitabine arm was 23.6 months while 5FU/leucovorin arm was 23 months [22]. This had shown that adjuvant gemcitabine had similar survival but less toxicity as compared to 5FU. At this point, there were now two different adjuvant treatment options for resected pancreatic cancer.
\nVan Hoof et al. (2013) performed a phase III trial in which metastatic pancreatic cancer patients were randomized to treatment with either nab-paclitaxel (125 mg per square meter of body surface area) plus gemcitabine (1000 mg per square meter) on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy (1000 mg per square meter) weekly for 7 of 8 weeks and then on days 1, 8, and 15 every 4 weeks. The overall survival in the nab-paclitaxel-gemcitabine was 8.5 months as compared to gemcitabine alone with 6.7 months (p > 0.001). This doublet therapy did result in higher rates of myelosuppression and peripheral neuropathy than gemcitabine alone [23]. While this study was based on patients with metastatic disease, it advanced the adjuvant combined chemotherapy regimen in resected pancreatic cancer.
\nThe ESPAC-4 went on to compare adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer. Capecitabine is an orally active fluoropyrimidine carbamate which can provide prolonged fluorouracil exposure at lower peak concentrations. The 5-year overall survival with gemcitabine and capecitabine compared to gemcitabine alone was 29% vs. 16% [24]. The new standard of care quickly adopted doublet therapy as the new standard of care.
\nThe use of adjuvant FOLFIRINOX [fluorouracil (5-FU), leucovorin, irinotecan, oxaliplatin] has been extrapolated from the treatment of pancreatic cancer in the metastatic setting. In the ACCORD-11 trial, FOLFIRINOX was found to have a superior survival advantage over gemcitabine in metastatic pancreatic patients with median overall survival of 11.1 months vs. 6.8 months [25]. This study ultimately launched FOLFIRINOX into new treatment paradigms in the adjuvant and neoadjuvant settings.
\nThe phase III PRODIGE 24/CCTG PA.6 trial compared a modified FOLFIRINOX regimen against single-agent gemcitabine therapy, as the results of the ESPAC-4 were not known at study design. This study used a modified FOLFIRINOX regimen: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and irinotecan 180 mg/m2 (dose reduced to 150 mg/m2 after patient 162) on day 1 and continuous fluorouracil infusion 2.4 gm/m2 over 46 hours. This regimen was repeated every 2 weeks for 12 cycles. The gemcitabine regimen was 1000 mg/m2 once per 3 of 4 weeks for 6 cycles [26]. The response rate was 31.18% in the mFOLFIRINOX group and 11.3% in the gemcitabine group. The disease-free survival (DFS) and overall survival (OS) in the mFOLFIRINOX arm were 21.6 and 54.4 months, while the gemcitabine arm were 17.7 and 35.0 months repetitively. Grade 3 or 4 adverse events (neutropenia, diarrhea, neuropathy) were significantly higher in the FOLFIRINOX treatment arm than the gemcitabine arm [26].
\nmFOLFIRINOX has been the largest advancement in overall survival for resected pancreatic cancer patients, which more than doubled the previous median overall survival.
\nThere are mixed opinions regarding the routine use of radiation therapy in pancreatic cancer. The ESPAC-1 did not reveal any significant survival benefit with chemoradiation [19]. A meta-analysis of five randomized controlled trials using adjuvant chemoradiation in patients who underwent curation resection was performed to assess the survival benefit. It appeared that adjuvant chemoradiation had benefitted the subset of patients with a positive margin status; however, it was not statistically significant [27].
\nThe RTOG study looks to determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation improved survival as compared with fluorouracil. Patients were given either fluorouracil (continuous infusion 250 mg/m2 per day) or 30 minutes infusion of gemcitabine (1000 mg/m2 once a week) for 3 weeks prior to fluorouracil chemoradiation and for 12 weeks following chemoradiation. The median survival for the gemcitabine group was 20.5 months, while the median survival for the fluorouracil group was 16.9 months. There appeared to be a survival benefit, but it was not statistically significant [28].
\nThe LAP07 randomized clinical trial aimed to assess if chemoradiation would improve overall survival after 4 months of gemcitabine and to assess erlotinib’s effect on survival as well as in patients with locally advanced pancreatic cancer. There was no difference in overall survival between the chemotherapy alone vs. the addition of chemoradiation, 16.5 months vs. 15.2 months [29].
\nWhile variations may occur at different institutions, a common approach for resectable pancreatic cancer would include the surgical resection of the cancer followed by adjuvant chemotherapy. The use of radiation may be used in the adjuvant setting for positive margins following chemotherapy after proving no metastatic disease developed.
\nFor patients that present with borderline resectable and locally advanced pancreatic cancer, neoadjuvant chemotherapy with or without chemoradiation allows for systemic control and may improve the likelihood of a R0 resection. The initial rationale for upfront therapies is to potentially downstage tumors to become resectable with a higher R0 resection rate and to allow potential latent metastatic disease to declare itself. In addition, the use of neoadjuvant chemoradiation may be used to “sterilize” the tumor margins near vessel involvement. This allows for selection of the most appropriate patients who have the highest likelihood of long-term survival.
\nBased on the ACCORD-11 trial showing superior response to FOLFIRINOX, this regimen has now been used effectively in the neoadjuvant setting for borderline and locally advanced pancreatic cancers. Several series have been published showing institutional success. The Massachusetts General Hospital reported that patients treated with mFOLFIRINOX have significantly smaller tumors and lower rates of lymphovascular invasion and perineural invasion. The R0 resection was 92% [30]. Similar reports from the Ohio State University were also noted. They were also able to convert locally advanced and unresectable pancreatic cancers to resectable in 51% of patients who underwent neoadjuvant mFOLFIRINOX with R0 resection of 86% [31].
\nWhile patients are undergoing neoadjuvant chemotherapy, serial imaging with pancreatic protocol CT is used to observe for treatment response. In those patients that develop metastatic disease or progression to unresectable disease while undergoing neoadjuvant, their poor biology of disease had declared itself, and they were spared the major morbidity of a surgical resection. For those demonstrating stable or treatment response, the radiologic imaging can be used to predict treatment response. The appearance of the tumor and pancreatic parenchyma interface that becomes more distinct indicates a cytotoxic response which ultimately translates to pathologic response. The ideal response is for the tumor to pull away from the vessels and no longer see haziness around the vessels, which may indicate an infiltrative process. Another prognostic marker of treatment response is normalization of CA 19–9 during neoadjuvant therapy [32].
\nA pathologic complete response (pCR) can be found in approximately 10% of patients treated in the neoadjuvant approach with FOLFIRINOX and chemoradiation. This is also an independent prognostic risk factor for improved overall and disease-free survival [33]. Additionally, small tumor size, negative margins, and negative lymph node metastasis are favorable prognostic indicators for improved overall and disease-free survival.
\nThe consensus for treatment of borderline resectable pancreatic cancer favors the neoadjuvant approach; however, it may vary per institution. After a multidisciplinary review at our hospital, the typical functional patient would undergo neoadjuvant chemotherapy (FOLFIRINOX) for 3–4 cycles followed by restaging with CT and CA 19–9. If stable or responding disease, then the patient would continue additional 3–4 cycles of FOLFIRINOX. The patient would again be restaged with CT and CA 19–9. Barring no metastatic disease developed and there was treatment response, the patient would then undergo surgical intervention. However, if the surgical margins were still threatened and there was concern for R1 resection, then the patient may undergo chemoradiation to “sterilize” the margins. Approximately 4–6 weeks after chemoradiation, the patient would ultimately undergo surgical resection.
\nUnresectable pancreatic cancer means that the tumor cannot safely be removed due to vascular involvement or metastatic disease. Patients may undergo aggressive chemotherapy with FOLFIRINOX, and a few may be able to convert to a resectable cancer. It is of utmost importance for early palliative care interventions in these patients. For those with biliary obstruction, the use of endoscopic biliary stents and percutaneous biliary drains may provide relief from the jaundice. If the tumor is found to be unresectable in the operating room, then palliative hepaticojejunostomy may be performed. Gastric outlet obstruction may also be relieved with endoscopically placed luminal stents. Additionally, surgical bypass may be performed in laparoscopic or open fashion with a gastrojejunostomy.
\nPain can also become quite debilitating in patients with locally advanced unresectable pancreatic cancer. Celiac plexus neurolysis can be performed at the time of surgical exploration, or it may be performed by endoscopic or percutaneous routes.
\nIrreversible electroporation (IRE) is a nonthermal ablative modality which relies on high voltage (maximum 3,000 volts) small microsecond pulse lengths. This is a novel option typically used in locally advanced pancreatic adenocarcinoma of the head or neck that is not amendable to resection. Some institutions are now using IRE to assist with the resection of locally advanced tumors, but this is not standard at this time. The procedure may be performed open or percutaneously. Patients will typical undergo several months of neoadjuvant chemotherapy to not miss occult metastatic disease prior to IRE. IRE can improve progression-free survival from 6 to 14 months and overall survival from 23 to 20 months [34].
\nThere are several active clinical trials investigating additional treatment options for pancreatic cancer. Several phase II trials are looking at the use of targeted agents in addition to systemic chemotherapy. One study is evaluating the safety of niraparib, PARP [poly (ADP-ribose) polymerase] inhibitor, in advanced pancreatic cancer patients [35]. Another clinical trial at the Massachusetts General Hospital is using the checkpoint inhibitor, nivolumab, as programed death-1 (PD-1) inhibition in combination with losartan, FOLFIRINOX, stereotactic body radiation therapy (SBRT), and surgery in advanced pancreatic cancer. This is a three-armed study: Arm 1 with FOLFIRINOX, SBRT, and then surgery; Arm 2 with FOLFIRINOX plus losartan, SBRT plus losartan, and then surgery; and Arm 3 with FOLFIRINOX plus losartan, SBRT plus nivolumab and losartan, and then surgery [36].
\nReviewing the past studies on chemoradiation, one must keep in mind these studies were using monotherapy chemotherapy and conventional fractionated radiation therapy. There are now several clinical trials assessing the role of radiation therapy, specifically SBRT in the setting of FOLFIRINOX. SBRT utilizes high doses of ablative radiotherapy in typically 1–5 fractions.
\nThe ALLIANCE A021501 is a randomized controlled trial using modified FOLFIRINOX regimen (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and infusional 5-fluorouracil 2400 mg/m2 over 2 days for 4 cycles) in borderline resectable pancreatic head adenocarcinomas. Arm 1 is delivering this regimen for 8 cycles, while Arm 2 is receiving 7 cycles followed by SBRT (33–40 Gy in 5 fractions). The patient then undergoes pancreaticoduodenectomy followed 4 cycles of adjuvant-modified FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, bolus 5-fluorouracil 400 mg/m2, and infusional 5-fluorouracil 2400 mg/m2 over 2 days for 4 cycles). The main aim of this study is to assess 18-month overall survival, R0 resection, and event-free survival [37].
\nAnother randomized controlled trial by the Pancreatic Cancer Radiotherapy Study Group (PanCRS) is assessing the progression-free survival between mFOLFIRINOX alone vs. mFOLFIRINOX and SBRT in locally advanced unresectable pancreatic cancer [38].
\nAlso, a novel class of drug, cancer stemness inhibitors, is being investigated as a potential new treatment for pancreatic cancer. Napabucasin is an oral small molecule that blocks stem cell activity by targeting the signal transducer and activator of transcription 3 pathway. This pathway is believed to be an important pathway in the propagation of stem-cell-mediated cancer cells [39].
\nWhile pancreatic cancer is still an aggressive malignancy which is often lethal, there have been significant improvements in the systemic chemotherapy which has improved patients’ overall survival. In addition, the radiographic quality has improved thus we are better able to appropriately stage patients for resectability from the onset. Future research in the use of targeted and immunotherapy and the promise of SBRT may control to improve the outcomes of pancreatic cancer patients. With the use of multidisciplinary treatment teams, aggressive combination chemotherapies and surgical resections, there is hope for the patients with pancreatic cancer.
\nThe authors declare that there are no conflicts of interest.
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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. 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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). 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