THESES PRINTING DESIGN THESIS MANUAL
Contents CONTENTS 00 01 02 03 04 05 06 07 08 GENERAL INFORMATION 9 SUBMIT THE THESIS YOURSELF 19 THE COVER 35 LAYOUT PACKAGES 43 ONLINE PUBLISHING 53 PAPER TYPES & EXTRA OPTIONS 57 CREATING PDF FILES 67 PROCESS & TIMELINES 7 FREQUENTLY ASKED QUESTIONS 85
3 About Us Who Are We? Ridderprint is a family business with years of experience in printing theses. We believe in close collaboration with PhD candidates to create a beautiful final product. A thesis is more than just a document; it marks the end of an important phase and deserves a unique and personalized design. With the latest techniques, we strive to always deliver the highest quality at fair prices. Together, we discuss the best options for design and printing to make the most out of every budget. We place great value on clear communication. That’s why you’ll have access to an online portal where you can track the entire process of your thesis, including design and planning. At Ridderprint, we make your thesis unique, reflecting your dedication and personal wishes. We look forward to a great collaboration! Pieter Neven Niek Verloop Fred van der Spek Robert Kanters Ellen Wang Proefschrift Specialist Proefschrift Specialist Order Manager Proefschrift Specialist Order Manager Ridderprint Team
THINK WITH US ABOUT OUR FUTURE
5 Our Future Sustainable Business At Ridderprint, we take our responsibility for sustainable business seriously. We are continuously seeking innovative and sustainable production methods to minimize our environmental impact. Our processes are ISO certified, and we use FSC paper, which means our paper comes from responsibly managed forests. Trees for All An important part of our sustainability efforts is the “From Paper to Forest” project, in collaboration with the Trees for All foundation. Through this initiative, we compensate for our organization’s CO2 emissions by planting trees in our own company forest. Additionally, Trees for All supports reforestation projects in Indonesia. Together with partners like Limburgs Landschap and Staatsbosbeheer, we contribute to the greening of Limburg. Thanks to the support of donors and partners, we are making a positive impact on nature and working towards a more sustainable future. Curious? Click on this link to our website for more information.
6 00 Collaboration Do you want to have your thesis printed at Ridderprint? After your approval, we will plan the project. In your personal online portal you will find the planning and all other information about your order. Submitting files You will find the submission guidelines in the online portal. We will check the files on a number of specific points and give you feedback where necessary. Based on this feedback, you can make any adjustments. Layout If you choose a layout package (see chapter 4), there will be an intake with a designer to discuss your wishes for the design and the delivery of files. After we have discussed your wishes, we will start the design process. Once this is completed, we will create files for the proof. Sending the proof When the files are approved and finalized, we will send you a complete proof by mail. As soon as the proof is sent, you will receive an email with track & trace information. For rush orders, we will send the proof digitally by email. Checking the proof Check the proof carefully and give your approval by email. Do you have any changes? Then send us the new files or your corrections to the designer. We will send a digital proof of the corrected files for your final approval. 1 Step 3 Step 4 Step How We Work On our website, www.ridderprint.nl, you can easily request an offer. We will contact you within 2 working days to discuss it. If you do the layout yourself and provide the files, the whole process can take 3 to 4 weeks. If the layout is done by us, the whole process takes 5 to 6 weeks. 5 Step Below you can see step by step how we work in this process: 2 Step
7 0 Process 1 Approval for production After approval of the final proof we will send you an order confirmation by email with the final specifications and costs of your order. After your review and approval we will start the production process. Production The production and delivery of the books takes 8 to 10 working days. If the planning is delayed for any reason due to (unexpected) changes, we will adjust the planning. Please note that this may affect the delivery date of your books. Delivery Your thesis will be carefully packed in boxes and shipped to the address you specified. Please ensure that someone is present between 08:00 and 17:00 on the agreed delivery date to receive the delivery. If no one is present, the shipment will be offered again the next working day. Please note that there are additional costs involved. 7 Step 8 Step 6 Step Process Timeline Planning Planning Files Intake Proof Layout Approval Proof Production Approval Production 1 week 3 weeks 1 week 2 weeks 1 week 2 weeks Submit yourself With a layout
01 GENERAL INFORMATION
01 10 As a thesis specialist, we keep a close eye on the latest developments in the field of production. We always want to have the best in-house. Printing Methods Digital printing Features: • Short delivery time. • Easy to order extra. • Ideal for theses with color pages. You pay per page and are not tied to sections as with offset printing. Offset printing Features: • Delivery time is one week longer than digital printing. • Attractive for quantities over 500. • Color pages can be expensive, depending on their position and quantity. This determines the number of sections that need to be printed in color. Finishing Methods Perfect Bind This is our standard finishing method. Loose sheets are joined together to form a book block, which is roughened in a machine with a milling cutter. The cover is then connected to the book block in flexible glue. Stich bound In this method, sheets are folded into sections, which are sewn together and then glued to the cover. This more sustainable method is less used due to its higher costs and longer production time.
General Information 11 1 Use of Color When you use photos, diagrams or other image elements in color, they are printed in ‘full color’, or CMYK (Cyan, Magenta, Yellow and Key=black). These are the 4 basic colors used for both digital and offset printing. RGB vs CMYK In programs like Word and Publisher, only PDF files can be generated that are in the RGB (red, green and blue) color space. A printer cannot print RGB colors and therefore converts the RGB information into a CMYK color space. Because the CMYK color space is much smaller than the RGB color space (see image below), colors can be converted to the closest color that can be printed. This can lead to color surprises: your file can appear brighter in RGB on your screen than in CMYK on paper. If you use professional software such as Adobe InDesign or Illustrator, try to work in CMYK color mode as much as possible. This gives a better visual representation of the final colors in your print. If your file is set up in RGB, we will automatically convert it to CMYK. Color differences Please note that colors may appear differently on your screen than on paper. This may be due to the brightness and contrast settings of your monitor. Different paper types can also affect how colors appear.
01 12 Image Quality Resolution Make sure the images in your thesis are of high quality. We recommend a resolution of at least 300 dpi (dots per inch). Of course, we check the quality of the images. Take note: Enlarging an image will reduce its resolution. If you double the size of an image with a resolution of 300 dpi, the effective resolution will drop to 150 dpi. However, reducing the size of an image can improve its resolution. Vector figures Vector graphics are scalable without loss of quality. They have no resolution and are not dependent on the number of pixels, which makes them ideal for line art, graphs, logos, etc. Because vector graphics have a small file size, they are also easy to process. Adobe Illustrator is an example of vector-oriented software, while Adobe Photoshop is pixel-oriented software. PowerPoint figures If you have created figures in Microsoft PowerPoint, you can supply them in vector quality. Save the figures as EMF (Enhanced Meta File). You can then easily place this file in your Word document.
General Information 13 1 300 DPI 72 DPI Totaal Zoom An image made up of pixels An image made up of vectors
01 14 Bleed In the submission instructions we ask for print files to include bleed, which is a margin that is necessary for the cutting process. If you have image elements, such as background photos, color areas or tabs, that extend to the edge of the page, these must be supplied with ‘bleed’. This means that these elements must extend at least 3 mm over the edge of the final page format, both top, bottom, left and right. This margin prevents white edges after cutting the printed matter. 149602 Jongeneel BNW.indd 18 04-06-2021 13:47 Page size + bleed 17,6 x 24,6 cm Bleeding background image Safe zone 5 mm (from final size) 3 mm will be trimmed off Final size (trim size) 17 x 24 cm
General Information 15 1 e the large number of RCTs that have evaluated adjuvant treatment effectiveness in colon cancer ts, the effectiveness in the stage II population remains unclear, mainly due to insufficient power studies for the stage II population. Furthermore, over the years the number of examined regional nodes per patients increased as this provides important information about the patients’ osis, which resulted in a migration of disease stage.9 That is, a patient that was classified as stage ore the increasing number of evaluated lymphnodes, could possibly be classified as stage III in a recently conducted study. Secondly, there is no consensus on which high-risk features should be into account to select stage II colon cancer patients for adjuvant chemotherapy. Thirdly, there is onvincing data for the optimal duration of adjuvant treatment in stage II colon cancer patients ared to stage III colon cancer. Moreover, when deliberating on the optimal treatment choice in II colon cancer, it is important to explicitly take into account the fact that there are also health associated with adjuvant chemotherapy. To guide the clinical decision making process, the tial health gain of adjuvant treatment should be carefully balanced against the potential harms. arizing, the identification of patients that require adjuvant chemotherapy as well as the optimal ment duration remains challenging. Below the three knowledge gaps are discussed in more detail. fect of adjuvant chemotherapy in stage II colon cancer eatment effect of adjuvant chemotherapy in stage II colon cancer has been evaluated in several mized clinical trials (RCTs) during the last decades. IMPACT was the first collaboration that cted a pooled analysis of 1,016 patients with stage II colon cancer from 5 RCTs, which compared rouracil-leucovorin (FU-LV) treated group to a control group. The group that was treated with demonstrated a small, statistically non-significant improvement in 5-year DFS and OS. The DFS were 76% versus 73% and the OS rates were 82% versus 80% for the FU-LV group compared to ntrol group, respectively.10 Subsequently, in 2004 another meta-analysis was conducted in which patients were included with stage II or III colon cancer from 7 RCTs (the 5 RCTs included in CT and two additional RCTs), which compared FU-LV to a control group. In a stage II colon cancer oup analysis (n=1,440), a small but significant difference of 4% (76% versus 72%, p=0.049) was for DFS and a small non-significant difference of 1% in OS (81% versus 80%, p=0.113).11 7, results of the QUASAR trial became available. In the QUASAR trial, 3,239 resected stage I (1%), %) and III (8%) patients were included of which 71% was diagnosed with colon cancer and 29% ectal cancer. Patients were randomized to a FU-LV arm (with or without levamisole) or a control The QUASAR trial demonstrated a relative risk of recurrence of 0.78 (95% CI, 0.67-0.91) and a e risk of OS of 0.82 (95% CI, 0.70-0.95) for FU-LV treated patients compared to observation. The rs reported an improvement in OS of 3.6% for FU-LV compared to observation within 5-year -up, which was assessed as having limited clinical impact.5 After the QUASAR trial, the MOSAIC SABP-07 trials were conducted to evaluate the benefit of the addition of oxaliplatin to FU-LV OX) in stage II and III colon cancer. In the secondary analysis of stage II colon cancer patients only 9), the MOSAIC trial reported a statistically non-significant improvement in DFS with a hazard HR) of 0.84 (95%CI: 0.62-1.14) for FOLFOX compared to FU-LV. However, the HR for OS was 1 CI: 0.70-1.41), indicating equal survival probabilities in both groups.12 In the NSABP C-07 trial, 1 General introduction CHAPTER 2 Estimating adjuvant treatment effects in stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data Gabriëlle Jongeneel, Thomas Klausch, Felice N. van Erning, Geraldine R. Vink, Miriam Koopman, Cornelis J.A. Punt, Marjolein J.E. Greuter and Veerle M.H. Coupé International Journal of Cancer. 2020 Jun 1;146(11):2968-2978 Estimating adjuvant treatment effects in stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data Gabrielle Jongeneel, Thomas Klausch, Felice N. van Erning, Geraldine R. Vink, Miriam Koopman, Cornelis J.A. Punt, Marjolein J.E. Greuter and Veerle M.H. Coupé International Journal of Cancer. 2020 Jun 1;146(11):2968-2978 CHAPTER 2 149602 Jongeneel BNW.indd 19 04-06-2021 13:47 Page with bleeding navigation tabs. The number is positioned 5 mm from the final trim size. Bleeding layout element
01 16 Paper Proof During the production process, you will receive a paper proof. You can assess this for content and quality. Please note that special applications, such as spot UV and foil printing, cannot be shown on this proof due to their high start-up costs and longer setup times. Reviewing PDF files We regularly send PDF files as a proof. For the best view, we recommend not opening these in a browser or preview mode, as this does not always provide a correct view. Use Adobe Acrobat Pro or the standard Acrobat version, and set it up so that the inside pages can be properly assessed. Color or Black and White Pages There are differences in costs for color and black and white pages. If you have pages that do not need to be in color, you can convert them to grayscale. If this does not work, we can do this for you. In the process, enter the page numbers of the color pages, for example: 12, 34, 56, etc. Note these page numbers Note these pages if Roman numerals are used in the front matter pages.
General Information 17 1 Submitting Files If you submit files yourself, we would like to receive technically correct PDF files. In chapter 7 you will find an explanation of how to create these files from various software packages. Ridderprint Online Portal At the start of the collaboration, you will receive login details for our online portal. Here you can upload files, view the planning and track the order status. Delivery options • Online Portal: www.ridderprint.nl/portal (you will receive login details). • WeTransfer Channel: ridderprint.wetransfer.com. • Email: Send files up to 20 MB to orders@ridderprint.nl stating your name and order number. File Names When Uploading When uploading, it is important to use clear file names to avoid confusion. Use a new version number or date when uploading a new version. File Name Examples: - “order number_last name_inside pages.pdf” - “order number_last name_inside pages_v2.pdf” - “order number_last name_cover.pdf” - “ordernr_complete.zip”
02 SUBMIT THE THESIS YOURSELF
02 20 In general, Microsoft Word is used to format the inside pages, because this program is standard on most computers. For a more professional format, you can also use Adobe InDesign. Below is an explanation of how to prepare your document in both programs. Layout of the Inside Pages Points of attention • White Margins: The white margins determine the width and height of the text block, excluding headers and footers, which may fall outside of this range. • Recommended white margin: A 2 cm white margin is recommended for all sides of a page (top, bottom, left and right). • Headers and Footers: Make sure that the headers and footers are at the same height on every page. • Page Numbers: Place page numbers on the left on even pages and on the right on odd pages. • Titles and Chapter Starts: Make sure title pages and new chapter start pages are on a right (odd) page. • Order of Front Matter: Please note the correct order of the front matter (see page 22). • File format: If you submit your file in A4 format, we will reduce it to 81% of the original size, resulting in a final size of 17 x 24 cm. The recommended minimum font size is 12 points, which after reduction is 10 points. • Bleed: If you have images that need to extend to the edge of the page, allow for bleed. (see page 14). • Images and Tables: Place images, tables, etc. as much as possible within the width of the text block. • Landscape pages: These are rotated 90 degrees counterclockwise. Note that this will cause the side margins to become the top and bottom margins and vice versa. • Image quality: Make sure that inserted images have a high resolution (see page 12).
2 Submit Yourself 21 Chapter 1 (header) 4 (footer) 5 Even page (left-side in the book) Odd page (right-side in the book) Page-layout inside inside Chapter Title Outside Outside TOP TOP BOTTOM BOTTOM RIGHT LEFT Margins in Microsoft Word LEFT RIGHT
02 22 The Front Matter The front matter must be in the correct order, although the content may vary per university. Consult the PhD regulations of your university for this. Page I - Title page Here you usually place a short title and possibly the name of the author. Page II - Colophon page Information such as ISBN, printer, copyright and any sponsors can be included here. Page III - Promotion page This is mandatory; consult your university’s promotion regulations for the correct text. Page IV - Doctoral Committee List the members of the doctoral committee here, in accordance with the guidelines of your university. The front matter pages do have page numbers, but the numbers are not visible.
2 Submit Yourself 23 Promotiecommissie Promotoren: Prof.dr. P.A.E. Sillevis Smitt Prof.dr. P. Heutink Overige leden: Prof.dr.ir. C.M. van Duijn Dr. V. Bonifati Dr. T. van Laar I IV II III Progressive Supranuclear Palsy expanding the clinical and genetic spectrum Laura Donker Kaat Progressive Supranuclear Palsy expanding the clinical and genetic spectrum Progressieve supranucleaire verlamming: verbreding van het klinisch en genetisch spectrum Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof. dr. H.G. Schmidt en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op vrijdag 2 december 2011 om 9:30 uur door Laura Donker Kaat geboren te Haarlem Financial support for the printing of this thesis was kindly provided by Erasmus University Rotterdam Parkinson Vereniging Boehringer Ingelheim B.V. UCB Pharma B.V. Teva Nederland B.V. Abbott B.V. GRIPP B.V. ISBN: 978-90-5335-481-0 The studies in this thesis were financially supported by the Prinses Beatrix Fonds (grant number 01-0128). Cover design: Ridderprint, the Netherlands Printing: Ridderprint, the Netherlands Copyright © 2011 by L. Donker Kaat
02 24 Subsequent Pages The order of the pages after the front matter is not fixed, but here are some tips to make your thesis clear and neat: Always place important pages, such as the start of a chapter, the preface, and your resume, on an odd page. This is the right side in a book and ensures a logical reading flow. Blanco Pagina This thesis focuses on the evaluation of the optimal allocation and duration of adjuvant chemotherapy in stage II colon cancer. Using decision-analytic modelling, we evaluated the cost-effectiveness of different strategies to allocate adjuvant chemotherapy in stage II colon cancer patients. In addition, we evaluated the optimal treatment duration in these patients. This chapter briefly describes colon cancer epidemiology and the importance of optimizing treatment strategies in stage II colon cancer. Subsequently, it explains why adjuvant chemotherapy allocation is considered as a medical dilemma in stage II colon cancer by discussing treatment effectiveness, the selection of high-risk patients, the optimal treatment duration and the health risks of adjuvant chemotherapy. Furthermore, the advantages of decision-analytic modelling to address the challenge of adjuvant chemotherapy allocation and optimal treatment duration in stage II colon cancer are discussed. Finally, the aims and outline of this thesis are described. Colon cancer Colon cancer is the fourth most commonly diagnosed cancer worldwide, after lung-, breast- and prostate cancer, with around 1.1 million new cases and 0.6 million deaths in 2018.1 The incidence of colon cancer varies widely by world region and is highest in western countries, which is probably due to differences in lifestyle compared to non-Western countries.1 Worldwide, the incidence and mortality rates are higher in men compared to women. In the Netherlands, colon cancer is an important health problem as well. The incidence has more than doubled in the last thirty years; from 4,600 new cases in 1989 to 9,800 cases in 2018.2 The average age of a colon cancer patient is 69 years at the moment of diagnosis. In addition, more than 30% of all newly diagnosed patients are aged 75 or older.2 Thus, colon cancer mainly affects elderly patients. Given the aging population in the Netherlands in combination with an unfavourable change in lifestyle, such as a decrease in physical activity and an increase in alcohol consumption, the risk to develop colon cancer is increasing. On the other hand, the Dutch colorectal cancer screening program was introduced in 2014, which hopefully will ensure a decrease in colon cancer mortality in the long term. Shift in colon cancer stage distribution Using the tumor-node-metastasis (TNM) system, four disease stages are distinguished to classify the extensiveness of colon cancer.3 In this thesis, we focus on stage II colon cancer, which means that the tumor has grown through the colon wall, but has not spread to regional lymph nodes or distant organs. The proportion of stage II colon cancer patients was 26% in 2018 in the Netherlands. Due to the introduction of the Dutch national colorectal cancer screening program, the proportion of stage II colon cancer patients slightly decreased. To illustrate, in 2013 28% of the colon cancer patients were diagnosed with stage II disease.4 Medical dilemma’s in stage II colon cancer treatment The standard treatment of stage II colon cancer patients is surgical resection. The overall prognosis after surgical resection is relatively good. To illustrate, the QUASAR trial reported in 2007 5-year survival rates of 76% and 80% for disease-free survival (DFS) and overall survival (OS), respectively.5 However, the stage II colon cancer population is heterogeneous regarding the risk to develop a recurrence. Therefore, adjuvant chemotherapy is recommended in national and international guidelines to optimize survival probabilities for those patients with a high risk of recurrence.6-8 Notwithstanding these recommendations, there are still three important knowledge gaps. Firstly, 8 1 Chapter 1 149602 Jongeneel BNW.indd 8 04-06-2021 13:47 This thesis focuses on the evaluation of the optimal allocation and duration of adjuvant chemotherapy in stage II colon cancer. Using decision-analytic modelling, we evaluated the cost-effectiveness of different strategies to allocate adjuvant chemotherapy in stage II colon cancer patients. In addition, we evaluated the optimal treatment duration in these patients. This chapter briefly describes colon cancer epidemiology and the importance of optimizing treatment strategies in stage II colon cancer. Subsequently, it explains why adjuvant chemotherapy allocation is considered as a medical dilemma in stage II colon cancer by discussing treatment effectiveness, the selection of high-risk patients, the optimal treatment duration and the health risks of adjuvant chemotherapy. Furthermore, the advantages of decision-analytic modelling to address the challenge of adjuvant chemotherapy allocation and optimal treatment duration in stage II colon cancer are discussed. Finally, the aims and outline of this thesis are described. Colon cancer Colon cancer is the fourth most commonly diagnosed cancer worldwide, after lung-, breast- and prostate cancer, with around 1.1 million new cases and 0.6 million deaths in 2018.1 The incidence of colon cancer varies widely by world region and is highest in western countries, which is probably due to differences in lifestyle compared to non-Western countries.1 Worldwide, the incidence and mortality rates are higher in men compared to women. In the Netherlands, colon cancer is an important health problem as well. The incidence has more than doubled in the last thirty years; from 4,600 new cases in 1989 to 9,800 cases in 2018.2 The average age of a colon cancer patient is 69 years at the moment of diagnosis. In addition, more than 30% of all newly diagnosed patients are aged 75 or older.2 Thus, colon cancer mainly affects elderly patients. Given the aging population in the Netherlands in combination with an unfavourable change in lifestyle, such as a decrease in physical activity and an increase in alcohol consumption, the risk to develop colon cancer is increasing. On the other hand, the Dutch colorectal cancer screening program was introduced in 2014, which hopefully will ensure a decrease in colon cancer mortality in the long term. Shift in colon cancer stage distribution Using the tumor-node-metastasis (TNM) system, four disease stages are distinguished to classify the extensiveness of colon cancer.3 In this thesis, we focus on stage II colon cancer, which means that the tumor has grown through the colon wall, but has not spread to regional lymph nodes or distant organs. The proportion of stage II colon cancer patients was 26% in 2018 in the Netherlands. Due to the introduction of the Dutch national colorectal cancer screening program, the proportion of stage II colon cancer patients slightly decreased. To illustrate, in 2013 28% of the colon cancer patients were diagnosed with stage II disease.4 Medical dilemma’s in stage II colon cancer treatment The standard treatment of stage II colon cancer patients is surgical resection. The overall prognosis after surgical resection is relatively good. To illustrate, the QUASAR trial reported in 2007 5-year survival rates of 76% and 80% for disease-free survival (DFS) and overall survival (OS), respectively.5 However, the stage II colon cancer population is heterogeneous regarding the risk to develop a recurrence. Therefore, adjuvant chemotherapy is recommended in national and international guidelines to optimize survival probabilities for those patients with a high risk of recurrence.6-8 Notwithstanding these recommendations, there are still three important knowledge gaps. Firstly, 8 1 Chapter 1 149602 Jongeneel BNW.indd 8 04-06-2021 13:47 despite the large number of RCTs that have evaluated adjuvant treatment effectiveness in colon cancer patients, the effectiveness in the stage II population remains unclear, mainly due to insufficient power in the studies for the stage II population. Furthermore, over the years the number of examined regional lymphnodes per patients increased as this provides important information about the patients’ prognosis, which resulted in a migration of disease stage.9 That is, a patient that was classified as stage II before the increasing number of evaluated lymphnodes, could possibly be classified as stage III in a more recently conducted study. Secondly, there is no consensus on which high-risk features should be taken into account to select stage II colon cancer patients for adjuvant chemotherapy. Thirdly, there is less convincing data for the optimal duration of adjuvant treatment in stage II colon cancer patients compared to stage III colon cancer. Moreover, when deliberating on the optimal treatment choice in stage II colon cancer, it is important to explicitly take into account the fact that there are also health risks associated with adjuvant chemotherapy. To guide the clinical decision making process, the potential health gain of adjuvant treatment should be carefully balanced against the potential harms. Summarizing, the identification of patients that require adjuvant chemotherapy as well as the optimal treatment duration remains challenging. Below the three knowledge gaps are discussed in more detail. The effect of adjuvant chemotherapy in stage II colon cancer The treatment effect of adjuvant chemotherapy in stage II colon cancer has been evaluated in several randomized clinical trials (RCTs) during the last decades. IMPACT was the first collaboration that conducted a pooled analysis of 1,016 patients with stage II colon cancer from 5 RCTs, which compared a fluorouracil-leucovorin (FU-LV) treated group to a control group. The group that was treated with FU-LV demonstrated a small, statistically non-significant improvement in 5-year DFS and OS. The DFS rates were 76% versus 73% and the OS rates were 82% versus 80% for the FU-LV group compared to the control group, respectively.10 Subsequently, in 2004 another meta-analysis was conducted in which 3,302 patients were included with stage II or III colon cancer from 7 RCTs (the 5 RCTs included in IMPACT and two additional RCTs), which compared FU-LV to a control group. In a stage II colon cancer subgroup analysis (n=1,440), a small but significant difference of 4% (76% versus 72%, p=0.049) was found for DFS and a small non-significant difference of 1% in OS (81% versus 80%, p=0.113).11 In 2007, results of the QUASAR trial became available. In the QUASAR trial, 3,239 resected stage I (1%), II (91%) and III (8%) patients were included of which 71% was diagnosed with colon cancer and 29% with rectal cancer. Patients were randomized to a FU-LV arm (with or without levamisole) or a control arm. The QUASAR trial demonstrated a relative risk of recurrence of 0.78 (95% CI, 0.67-0.91) and a relative risk of OS of 0.82 (95% CI, 0.70-0.95) for FU-LV treated patients compared to observation. The authors reported an improvement in OS of 3.6% for FU-LV compared to observation within 5-year follow-up, which was assessed as having limited clinical impact.5 After the QUASAR trial, the MOSAIC and NSABP-07 trials were conducted to evaluate the benefit of the addition of oxaliplatin to FU-LV (FOLFOX) in stage II and III colon cancer. In the secondary analysis of stage II colon cancer patients only (n=899), the MOSAIC trial reported a statistically non-significant improvement in DFS with a hazard ratio (HR) of 0.84 (95%CI: 0.62-1.14) for FOLFOX compared to FU-LV. However, the HR for OS was 1 (95% CI: 0.70-1.41), indicating equal survival probabilities in both groups.12 In the NSABP C-07 trial, 2,409 patients (29% stage II and 71% stage III) were included. In a separate stage II analysis (n=695), HRs of 0.94 (95% CI: 0.70-1.26) and 1.04 (95%: 0.72-1.50) for DFS and OS, respectively, were found when comparing FOLFOX to FU-LV.13 1 9 General introduction 149602 Jongeneel BNW.indd 9 04-06-2021 13:47 Blank page
2 Submit Yourself 25 *Blank page or with an image/ illustration This thesis focuses on the evaluation of the optimal allocation and duration of adjuvant chemotherapy in stage II colon cancer. Using decision-analytic modelling, we evaluated the cost-effectiveness of different strategies to allocate adjuvant chemotherapy in stage II colon cancer patients. In addition, we evaluated the optimal treatment duration in these patients. This chapter briefly describes colon cancer epidemiology and the importance of optimizing treatment strategies in stage II colon cancer. Subsequently, it explains why adjuvant chemotherapy allocation is considered as a medical dilemma in stage II colon cancer by discussing treatment effectiveness, the selection of high-risk patients, the optimal treatment duration and the health risks of adjuvant chemotherapy. Furthermore, the advantages of decision-analytic modelling to address the challenge of adjuvant chemotherapy allocation and optimal treatment duration in stage II colon cancer are discussed. Finally, the aims and outline of this thesis are described. Colon cancer Colon cancer is the fourth most commonly diagnosed cancer worldwide, after lung-, breast- and prostate cancer, with around 1.1 million new cases and 0.6 million deaths in 2018.1 The incidence of colon cancer varies widely by world region and is highest in western countries, which is probably due to differences in lifestyle compared to non-Western countries.1 Worldwide, the incidence and mortality rates are higher in men compared to women. In the Netherlands, colon cancer is an important health problem as well. The incidence has more than doubled in the last thirty years; from 4,600 new cases in 1989 to 9,800 cases in 2018.2 The average age of a colon cancer patient is 69 years at the moment of diagnosis. In addition, more than 30% of all newly diagnosed patients are aged 75 or older.2 Thus, colon cancer mainly affects elderly patients. Given the aging population in the Netherlands in combination with an unfavourable change in lifestyle, such as a decrease in physical activity and an increase in alcohol consumption, the risk to develop colon cancer is increasing. On the other hand, the Dutch colorectal cancer screening program was introduced in 2014, which hopefully will ensure a decrease in colon cancer mortality in the long term. Shift in colon cancer stage distribution Using the tumor-node-metastasis (TNM) system, four disease stages are distinguished to classify the extensiveness of colon cancer.3 In this thesis, we focus on stage II colon cancer, which means that the tumor has grown through the colon wall, but has not spread to regional lymph nodes or distant organs. The proportion of stage II colon cancer patients was 26% in 2018 in the Netherlands. Due to the introduction of the Dutch national colorectal cancer screening program, the proportion of stage II colon cancer patients slightly decreased. To illustrate, in 2013 28% of the colon cancer patients were diagnosed with stage II disease.4 Medical dilemma’s in stage II colon cancer treatment The standard treatment of stage II colon cancer patients is surgical resection. The overall prognosis after surgical resection is relatively good. To illustrate, the QUASAR trial reported in 2007 5-year survival rates of 76% and 80% for disease-free survival (DFS) and overall survival (OS), respectively.5 However, the stage II colon cancer population is heterogeneous regarding the risk to develop a recurrence. Therefore, adjuvant chemotherapy is recommended in national and international guidelines to optimize survival probabilities for those patients with a high risk of recurrence.6-8 Notwithstanding these recommendations, there are still three important knowledge gaps. Firstly, 8 1 Chapter 1 149602 Jongeneel BNW.indd 8 04-06-2021 13:47 CHAPTER 2 Estimating adjuvant treatment effects in stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data Gabriëlle Jongeneel, Thomas Klausch, Felice N. van Erning, Geraldine R. Vink, Miriam Koopman, Cornelis J.A. Punt, Marjolein J.E. Greuter and Veerle M.H. Coupé International Journal of Cancer. 2020 Jun 1;146(11):2968-2978 Estimating adjuvant treatment effects in stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data Gabrielle Jongeneel, Thomas Klausch, Felice N. van Erning, Geraldine R. Vink, Miriam Koopman, Cornelis J.A. Punt, Marjolein J.E. Greuter and Veerle M.H. Coupé International Journal of Cancer. 2020 Jun 1;146(11):2968-2978 CHAPTER 2 149602 Jongeneel BNW.indd 19 04-06-2021 13:47 despite the large number of RCTs that have evaluated adjuvant treatment effectiveness in colon cancer patients, the effectiveness in the stage II population remains unclear, mainly due to insufficient power in the studies for the stage II population. Furthermore, over the years the number of examined regional lymphnodes per patients increased as this provides important information about the patients’ prognosis, which resulted in a migration of disease stage.9 That is, a patient that was classified as stage II before the increasing number of evaluated lymphnodes, could possibly be classified as stage III in a more recently conducted study. Secondly, there is no consensus on which high-risk features should be taken into account to select stage II colon cancer patients for adjuvant chemotherapy. Thirdly, there is less convincing data for the optimal duration of adjuvant treatment in stage II colon cancer patients compared to stage III colon cancer. Moreover, when deliberating on the optimal treatment choice in stage II colon cancer, it is important to explicitly take into account the fact that there are also health risks associated with adjuvant chemotherapy. To guide the clinical decision making process, the potential health gain of adjuvant treatment should be carefully balanced against the potential harms. Summarizing, the identification of patients that require adjuvant chemotherapy as well as the optimal treatment duration remains challenging. Below the three knowledge gaps are discussed in more detail. The effect of adjuvant chemotherapy in stage II colon cancer The treatment effect of adjuvant chemotherapy in stage II colon cancer has been evaluated in several randomized clinical trials (RCTs) during the last decades. IMPACT was the first collaboration that conducted a pooled analysis of 1,016 patients with stage II colon cancer from 5 RCTs, which compared a fluorouracil-leucovorin (FU-LV) treated group to a control group. The group that was treated with FU-LV demonstrated a small, statistically non-significant improvement in 5-year DFS and OS. The DFS rates were 76% versus 73% and the OS rates were 82% versus 80% for the FU-LV group compared to the control group, respectively.10 Subsequently, in 2004 another meta-analysis was conducted in which 3,302 patients were included with stage II or III colon cancer from 7 RCTs (the 5 RCTs included in IMPACT and two additional RCTs), which compared FU-LV to a control group. In a stage II colon cancer subgroup analysis (n=1,440), a small but significant difference of 4% (76% versus 72%, p=0.049) was found for DFS and a small non-significant difference of 1% in OS (81% versus 80%, p=0.113).11 In 2007, results of the QUASAR trial became available. In the QUASAR trial, 3,239 resected stage I (1%), II (91%) and III (8%) patients were included of which 71% was diagnosed with colon cancer and 29% with rectal cancer. Patients were randomized to a FU-LV arm (with or without levamisole) or a control arm. The QUASAR trial demonstrated a relative risk of recurrence of 0.78 (95% CI, 0.67-0.91) and a relative risk of OS of 0.82 (95% CI, 0.70-0.95) for FU-LV treated patients compared to observation. The authors reported an improvement in OS of 3.6% for FU-LV compared to observation within 5-year follow-up, which was assessed as having limited clinical impact.5 After the QUASAR trial, the MOSAIC and NSABP-07 trials were conducted to evaluate the benefit of the addition of oxaliplatin to FU-LV (FOLFOX) in stage II and III colon cancer. In the secondary analysis of stage II colon cancer patients only (n=899), the MOSAIC trial reported a statistically non-significant improvement in DFS with a hazard ratio (HR) of 0.84 (95%CI: 0.62-1.14) for FOLFOX compared to FU-LV. However, the HR for OS was 1 (95% CI: 0.70-1.41), indicating equal survival probabilities in both groups.12 In the NSABP C-07 trial, 2,409 patients (29% stage II and 71% stage III) were included. In a separate stage II analysis (n=695), HRs of 0.94 (95% CI: 0.70-1.26) and 1.04 (95%: 0.72-1.50) for DFS and OS, respectively, were found when comparing FOLFOX to FU-LV.13 1 9 General introduction 149602 Jongeneel BNW.indd 9 04-06-2021 13:47 CHAPTER 3 Chapter Breaks Does a chapter end on an odd page (right)? Add a blank* even page before the start of the next chapter. This way, each new chapter starts again on an odd (right) page. You can also apply this to other sections, such as the preface or your resume. Take note! Adding blank pages will affect page numbering. After adding these pages, always check the table of contents and adjust the numbering where necessary.
02 26 Colophon Page Copyright In the colophon you can place a copyright notice with the symbol ©, the year of publication and the name of the author. This protects your work, and others must ask permission to use parts of it. ISBN If your thesis needs to be registered, an ISBN is required. Please indicate this in your offer request. You can also request an ISBN from your university, so inquire about this first. With an ISBN, your thesis will be included in a globally recognized database, which increases its findability. DOI Nowadays, a DOI is important for the online findability of your thesis. Ask your university if they can request an ISBN or DOI. A DOI is a unique number that is assigned to a digital document and ensures that the document is always findable online, even if the internet address changes. Mention Ridderprint in the colophon If you want to mention Ridderprint as a printer, you can do so as follows: Printing: Ridderprint, www.ridderprint.nl Lay-out: Ridderprint, www.ridderprint.nl
2 Submit Yourself 27 ISBN Request You can request an ISBN via Ridderprint; you can indicate this when requesting an offer. What is an ISBN? An ISBN (International Standard Book Number) is a unique 13-digit code assigned to a book publication. By means of a NUR code, you indicate in which category your book falls when applying. This ensures that your publication can be found worldwide for (online) bookstores and libraries, as well as for people specifically looking for your topic. Is an ISBN required? An ISBN is not required if you sell your book exclusively via your own website or social media. However, the ISBN is a valuable addition to the findability of your work. Why should I apply for an ISBN? For many bookstores and online sales platforms, an ISBN is a requirement to include your work in their assortment. Among other things, it makes inventory management easier. Please note: an ISBN does not automatically mean that a barcode will appear on your book; for sales, a barcode is recommended. Do I need an ISBN for an e-book? Yes, for sales through regular online bookstores (such as iBooks) an ISBN for an e-book is required. However, if you only sell through your own website or social media, an ISBN is not required. Can I use the same ISBN for both the paper version and the e-book? No, each format requires its own ISBN. A paper book, e-book and other variants each get a separate code. When should I apply for a new ISBN? For each new publication form (such as paperback, hardback or e-book) a separate ISBN is required. Also if the content of a reprint changes, a new ISBN must be requested.
02 28 Formatting in Microsoft Word For theses, a standard format of 17 x 24 cm is almost always used. However, the layout is often done in A4 format with the associated standard settings and margins. Formatting a thesis in A4 format We can reduce your document to 81%, so that it matches the final size of 17 x 24 cm. Please note the following points: • Margins: Use recommended margins of 2.5 cm all around on A4 format. • Text size: Keep the base font size at 12 points. After shrinking, this will be about 10 points, which is our recommendation for the final size. • Other text elements: Adjust the size of headers, footers, captions, and text in tables so that they remain legible even after being resized. • Test the end result: Print a few pages at 81% to get an impression of the result. You can then judge whether the font size needs to be adjusted. Here are some examples per format with recommended margins: Format 17 x 24 cm Set the page size to 17 x 24 cm White margins Top 2 cm Bottom 2 cm Inside 2 cm Outside 2 cm Format A4 Set the page size to 21 x 29,7 cm White margins Top 2,3 cm Bottom 2,3 cm Inside 2,3 cm Outside 2,3 cm Format A5 Set the page size to 14,8 x 21 cm White margins Top 2 cm Bottom 2 cm Inside 2 cm Outside 2 cm Format 16 x 24 cm Set the page size to 16 x 24 cm White margins Top 2 cm Bottom 2 cm Inside 2 cm Outside 2 cm
2 Submit Yourself 29 Settings for A4 size with recommended margins 2,8 2,8 2,8 2,8 When using headers and footers, select the option “Different Odd and Even Pages.” This will position them on the outside: for even pages on the left and for odd pages on the right.
02 30 Formatting in Microsoft Word with Bleed Bleed cannot be set directly in Word, but you can create this effect by enlarging the page by 3 mm on all sides. It is important to compensate for this expansion in the white margins, because the bleed is not part of the content layout. Make sure that any content that needs to extend to the edge of the page, such as images or graphics, is placed close to the edge of the page or enlarged to reach this edge. Please note that these will be cut off 3 mm after printing. Therefore, do not place important text or elements too close to the edge of the page to avoid loss of content. Here are some examples per format to make a file with bleed: Format 17 x 24 cm with bleed Set the page size to 17 x 24 cm (Standard B5 size in Word). White margins Top 2,5 cm Bottom 2,5 cm Inside 2,3 cm Outisde 2,3 cm Set “From Edge” to: Header and footer 1,75 cm. Format A4 with bleed Set the page size to 21 x 29,7 cm. White margins Top 2,5 cm Bottom 2,5 cm Inside 2,5 cm Outisde 2,5 cm Set “From Edge” to: Header and footer 1,75 cm. Format A5 with bleed Set the page size to 15,4 x 21,6 cm. White margins Top 2 cm Bottom 2 cm Inside 2 cm Outisde 2 cm Set “From Edge” to: Header and footer 1,75 cm. Format 16 x 24 cm with bleed Set the page size to 16,6 x 24,6 cm. White margins Top 2 cm Bottom 2 cm Inside 2 cm Outisde 2 cm Set “From Edge” to: Header and footer 1,75 cm.
2 Submit Yourself 31 Settings for size 17 x 24 cm with recommended margins 25 cm 25 cm 23 cm 23 cm When using headers and footers, set both “From Edge” margins to 1.75 cm. This space between the header/ footer and paper edge needs adjustment to compensate for the bleed area.
02 32 Layout in Adobe InDesign When creating a new document in Adobe InDesign, you can set the ‘bleed area’. This is indicated by a red line outside the final format of the document (black line). All elements that should extend to the edge of the page should reach this red line. Please note that the 3 mm space outside the black lines is not part of the content layout and will be cropped later. Make sure that any text or elements that you do not want to lose are at least 5 mm away from the page edge. Once you have finished formatting, export the document as a PDF file with bleed and crop marks. Instructions for this process can be found on page 78 of this manual. Create a document in InDesign: 1. Open a new document with a size of 170 x 240 mm. 2. Check the ‘pages facing each other’ option. 3. Set the margins to 20 mm. 4. Set the bleed area to 3 mm. Make sure headers and footers remain at least 5 mm from the page edge (green line). Tip Keep the base text between 9 and 10 points. Print a few pages at 100% to get an idea of the final result. Adjust the font size if necessary, and take into account the dimensions of other text elements, such as headers, footers, captions, and text in tables.
2 Submit Yourself 33 Page setup in Adobe InDesign Chapter 1 Chapter Title 4 5 margins page edge (document) bleed area Adobe InDesign Document Settings for a 17 x 24 cm book
THE COVER 03
36 03 For cover design, Adobe InDesign, Illustrator, or Photoshop are commonly used. InDesign excels in layout design, Illustrator handles illustrations and vectors, and Photoshop is great for photo editing. This section provides guidelines on using these tools to create a professional cover design that meets the necessary technical specifications. Cover Layout If you are creating the cover yourself, please keep to the following guidelines (see page 38): • The total width of the document is equal to your book size plus the spine thickness and 6 mm (bleed). • Please submit the PDF as a single page (spread). • Make sure that bleed elements extend to the edge of the page, with a 3 mm bleed. • The correct spine thickness depends on the type of paper and the number of pages. Information on calculating the spine thickness can be found in your portal. • Images must be of high quality (minimum 300 DPI, maximum 600 DPI). • Do not place important images or text too close to the edge of the page (see safe area). • Want to print the inside of the cover? See page 39 for specifications. • Interested in a bookmark as an invitation? Look for submission instructions on our website or in your portal. Cover in Adobe InDesign or Illustrator 1. Create a document with a total width equal to the back, spine, and front of the book. 2. Specify the 3 mm bleed in the document. This line will be displayed in red outside the document size (black line). Make sure that background colors or images extend to this line. 3. The dotted lines indicate a safe margin of 10 mm. Use the specifications of the attached screenshots (margins); this line is magenta. Place text and image elements within this margin without any problems. 4. Export the document as PDF with bleed and crop marks. Instructions for this can be found from page 78 of this manual.
37 3 Cover Author Book Title subtitle Book Title back front safe margin 10 mm final book size (after trimming) document size with 3 mm bleed Height + bleed Back + spine + front + bleed Cover Settings for a 17 x 24 cm Book with 11 mm Spine
38 03 Cover | Guidelines for the Front SOFTCOVER GUIDELINES SPINE: YOUR BOOK TITLE GOES HERE YOUR NAME FRONT SIDE BACK SIDE 10 mm 3 mm SPINE WIDTH CLICK HERE TO CALCULATE YOUR BOOK TITLE GOES HERE YOUR NAME BOOK TITLE SUBTITLE fold margin 6 mm 240 mm (after trimming) book height + 6 mm 170 mm (after trimming) book width x2 (front+back) + spine width + 6 mm safe margin 10 mm final size
39 3 Cover Cover | Guidelines for the Inside SOFTCOVER GUIDELINES 170 mm (after trimming) 240 mm (after trimming) 4 mm 3 mm A BACK OF INSIDE FRONT OF INSIDE 4 mm book width x2 (front+back) + spine width + 6 mm book height + 6 mm
40 03 HEALTHY AGEING: HEALTH PROMOTION FOR PEOPLE WITH FRAILTY AND CHRONIC CONDITIONS | Xuxi Zhang HEALTHY AGEING HEALTH PROMOTION FOR PEOPLE WITH FRAILTY AND CHRONIC CONDITIONS Xuxi Zhang 143881 Zhang R14,5 OMS.indd 2-3 27-07-20 08:43 Social Communication in Young Children with Sex Chromosome Trisomy | Evelien Urbanus Social Communication in Young Children with Sex Chromosome Trisomy Neurocognitive Building Blocks of Behavioral Outcomes Evelien Urbanus 155824_Urbanus_R12,5_OMS.indd 2-3 19-07-2022 13:42
www.ridderprint.nlRkJQdWJsaXNoZXIy MTk4NDMw