Late effects awareness website for pediatric survivors of acute lymphocytic leukemia

Objectives Every day 43 children are newly diagnosed with cancer. Fortunately, almost 90% of these childhood cancer patients will survive. However, 60–90% of these survivors will experience late effects, health problems that occur months or years after treatment has ended. Late effects could occur as a result of the disease, its treatment, and patient-related factors. The two main objectives of this research are to: 1) Examine the existence of all web-based resources for childhood cancer survivors with acute lymphocytic leukemia which focus on medical and psychological aspects of late effects, and 2) Create an innovative website specifically designed to fill this void. Materials and methods A systematic literature review, followed by input from >20 different organizations, resulted in the creation of LEAP3 AHEAD (Late Effects Awareness for Patients, Physicians and the Public; Advancing Health and Eliminating All Disparities), a multi-dimensional website centering on late effects. Results An extensive review revealed 14 pediatric cancer websites, none of which focused exclusively on late effects. LEAP3 AHEAD is the first interactive website for acute lympocytic leukemia childhood cancer survivors and families, as well as physicians, and the public to: a) increase awareness about risks, detection, diagnosis, treatment, and prevention of medical and psychological late effects, b) provide suggestions to successfully reintegrate into schools, careers, and socially, and c) present opportunities including camps, scholarships, and pet therapy programs. Conclusion LEAP3 AHEAD is the first national website to provide a comprehensive, accessible, affordable, and multi-dimensional resource for pediatricians, internists, nurse practitioners, psychologists, survivors and their families, as well as the public about late effects.


Introduction
Each year, cancer kills more children between 1 and 20 years of age than asthma, diabetes, cystic fibrosis, and AIDS combined [1]. In 2014, there were 15,780 new cancer cases in children between the ages of 0-19 years [2].
The most common types of cancer in children 0-14 years of age are acute lymphocytic leukemia (accounting for 29% of all childhood cancers), brain and central nervous system (26%), neuroblastoma (6%), Wilms tumor (5%) and non-Hodgkin lymphoma (5%) [3]. Among adolescents age 15-19 years, Hodgkin lymphoma, thyroid carcinoma, brain and central nervous system and testicular germ cell tumors are the most prevalent [4]. Childhood cancer occurs randomly and cuts across all ethnic groups, socioeconomic classes and geographic regions in the U.S.
While treatment advances have increased the survival rate for many childhood cancers, it is still the leading cause of death by disease past infancy among children in the US [5]. Nevertheless, more than 80% of children and adolescents diagnosed with cancer will live at least five years after their diagnosis [6]. Regular, life-long follow-up care is vital because childhood cancer survivors are at risk for late effects. A total of 60-90% of survivors experience late effects [7]-complications, disabilities or other adverse outcomes as a result of the disease, its treatment, or patient-related factors [8] (Table 1). Late effects can occur months or years after treatment, vary widely, and can be physical, cognitive, or psychological in nature. Common late effects include: neuro-cognitive, cardiac, endocrine, and reproductive disorders, obesity and dyslipidemia, bone issues, second malignant neoplasms, and psychosocial problems (e.g., mood, feelings, actions, thinking, learning and memory, social and psychological adjustment) [7]. Childhood cancer survivors are unaware of where to obtain medical care for health issues such as late effects, which may follow cancer treatment [9]. Additionally, pediatricians and other health care providers (i.e., family physicians, internists, nurse practitioners, and physician assistants) may not be knowledgeable about recognizing or caring for late effects [10][11].
There is also a void in the public's awareness of pediatric cancers and late effects. Currently, there is no resource for physicians, patients or the public that comprehensively address late effects in cancer survivors of different racial/ethnic groups and ages. Given the expanding numbers of pediatric cancer survivors, there is a necessity for developing a mechanism to increase awareness of early detection, treatment, and amelioration of pediatric cancers' late effects.
Thus, the two main objectives of this descriptive study are to 1) Examine the existence of all web-based resources for childhood cancer survivors with acute lymphocytic leukemia which focus on medical and psychological aspects of late effects, and 2) to create an innovative website specifically designed to educate the general public, pediatricians and other health care providers, and childhood cancer survivors (of all ages) about late effects. The name of this website is LEAP 3 AHEAD: Late Effects Awareness for the Physicians, Patients, specifically, survivors with acute lymphocytic leukemia, and the Public: Advancing Health and Eliminating All Disparities.

Overview
A systematic literature search of PubMed/Medline and Web of Science core collection databases were performed for studies published until January 2017, using the search terms, childhood cancer, pediatric cancer, pediatric cancer survivors, websites, late effects, long-term effects, childhood cancer resources, and pediatric cancer resources. No relevant articles were identified regarding existing websites on late effects. Hence, Google and Google Scholar were used to locate relevant websites containing information on late effects among childhood cancer survivors. As a final approach, references about existing websites were obtained from our advisory panel, which consisted of community group representatives. They added great richness about how to practically approach, engage, and successfully collaborate with the community in order to develop a meaningful website that appealed to diverse populations. The websites provided in Table 2 are the result of the exhaustive web search and the advisory panel's expertise in the area.
The advisory panel reviewed and critiqued the description and evaluation of the websites. They determined whether the websites were: 1) specific for late effects among childhood cancer survivors, 2) user friendly, 3) attractive, 4) easy to comprehend for the specific sample, and 5) sources for relevant resources. The advisory panel were vigilant about creating a website that appealed to all ages, educational abilities, with the option to translate into several languages. The general public was included to increase awareness about late effects among the entire population.

Development of the LEAP 3 AHEAD website
The LEAP 3 AHEAD website was developed after comprehensively reviewing the literature and receiving input from a coalition consisting of both existing and new organizations in San Diego. The existing group included pediatric oncologists at Rady's Children's Hospital, and members from several established organizations, including American Cancer Society, MANA (short for "hermana," the only national Latino organization that focuses on pediatric oncology), Union Pan Asian Community, and San Diego Black Nurses Association. The new The members of the advisory group were chosen because of their interest and dedication to pediatric cancer, their willingness to participate, their availability to attend meetings, and their location (residing in California). All meetings were held at the Rebecca and John Moores Comprehensive Cancer Center, UCSD from January 2011 to May 2013. The participating organizations provided input and suggestions related to the website contents and layout, cultural and linguistic suitability, educational and outreach materials, translational and cultural adaptation, dissemination of the information, and website evaluation over the course of one year. After multiple revisions, the final website was completed, pilot-tested by cancer survivors, family members, and people in the community, and then refined.
Set up of website. The contents of the website were developed for five different childhood cancer survivor age groups including: youth (0-10 years) and their parents, tweens (11-17 years), young adults (18-25 years), adults (> 25 years), as well as for physicians and the public based on feedback from the advisory committee, people in the community and parents and childhood cancer survivors.
Symptoms and diagnosis, treatment, and prevention of late effects are featured on the website under the physical and emotional health (medical) tab for each age group. By hovering the mouse over a particular part of the body where the individual is experiencing pain or discomfort, the web user can easily identify their symptoms and potential diagnosis. The participant is able to click on dental, cardiac, endocrine, gastrointestinal, musculoskeletal, neurological, pulmonary, reproductive, and sensory systems. For example, if the survivor suffers from a headache, they would move the mouse to the head or neurological part of the diagram and the popup box would lead them from symptoms to a potential diagnosis, treatment, and preventive strategies. At present, the medical information is directed towards acute lymphocytic leukemia, since it is the most common type of pediatric cancer. In the future, other types of pediatric cancers will be included in the website.
Reintegrating back into life after completing cancer treatment can be challenging for childhood cancer survivors. For child, tween, and young adult survivors there are obstacles when interacting with friends, coworkers, and families as well as returning to/re-entering school or university or the professional environment (e.g., work setting). LEAP 3 AHEAD provides potential suggestions for cultivating relationships and achieving success at work and school. Information on other opportunities including pediatric cancer survivor camps, scholarships, alternative care (yoga) and companion animals are also offered on the website. Finally, the website contains music and contributed art and poetry created by pediatric cancer survivors.
Appearance. Efforts were made to create an interactive website with an attractive logo, tag line, bright colors, interactive images, which were approved by the participating organizations. The website has two links entitled "Educate Yourself," and "Educate Your Community." The latter provides a ready-to-use educational outreach packet for community leaders to post, hand out, place in a newsletter, or use in a talk.
All website and written materials were checked for content, literacy demand (e.g., reading grade level, vocabulary, learning aids, graphics, and layout) learning stimulation and motivation, and cultural competence. The messages were consistent, recognizable, and used language that enhanced health literacy. All materials were translated into Spanish. In the future, this website will be translated into additional languages, such as Chinese, Tagalog, Japanese, and Korean.
Target population. The initial target population consisted of San Diego and Imperial County residents, which has a diverse background, characterized by various cultural beliefs, socioeconomic conditions, and languages. The website was targeted towards cancer patients/ survivors and their families, residents who are interested in this information, those at high risk for developing childhood cancer, as well as all individuals who would benefit from an enhanced awareness of childhood cancer late effects. Particular attention was devoted to underserved populations, including those who lack adequate health insurance.
The second audience consisted of the professional community, who also required increased awareness and education. They include groups involved in any aspect of childhood cancer prevention, detection, or treatment, including health practitioners, nurse practitioners and physician assistants, community leaders, and faith-based leaders, as well as professional societies and volunteer organizations such as St. Baldrick's Foundation, LiveStrong, and the American Cancer Society. These groups require increased cultural competency to provide patients with the best standard of care.
Dissemination. In order to effectively reach low income and ethnically diverse segments, media communication venues will be utilized as well such as newspapers, magazines, flyers, radio, and TV. This includes Twitter, Facebook, Instagram, and Snapchat in order to reach younger generations.

Extensive literature review of existing web-based resources
There are several well-established websites and programs for childhood cancer survivorship, but none devoted exclusively to late effects, with resources available to survivors, families, health care providers and the public. Currently, there are fifteen websites in existence ( Table 2) that contain some information on late effects; albeit, this is not the main focus of any of the databases. Rather, they are based on childhood cancer and directed towards diverse audiences including cancer patients and survivors, families and friends, scientists, researchers, professionals, and advocates. Table 2 contains summary information regarding the source, targeted audience(s) (e.g., patients, physicians), population (s) of interest (e.g., cancer patients vs. survivors), translation into additional languages, disparities, medical and psychological late effects, available resources, and overall appearance of the fifteen websites. All websites concentrate on pediatric cancers survivors, primarily in their twenties, apart from the Ulman Foundation, which centers on adolescents and young adults with cancer (AYA) and Children's Oncology Group which encompasses pediatric, adolescent, and young adult cancer survivors. Cure-Search targets the greatest audience, including patient, family, friends, but not the general public.
Only one website, Ulman Foundation, broaches disparity. They describe young adults as an underserved population and provide two pages of statistics. No other website tackles disparity related information. CureSearch contains the greatest detailed information for cancer survivors on the most common late effects, specifically medical complications categorized by organ system (but not by specific type of childhood cancer), finances, and healthcare navigation (e.g., finding a healthcare team, paying for healthcare). In contrast, KidsHealth and National Children's Cancer Society explain late effects specific to the patient's own cancer diagnosis and treatment. Children's Oncology Group is superior for providing extensive information for health care professionals. Cancer.org discusses who is at risk for and what causes late effects, treatment effects on growth and development, fertility, and emotional issues. Fertile Hope deals exclusively with fertility related late effects. The National Coalition for Cancer Survivors contains no specific information for pediatric late effects, other than on blood cancer late effects. Additionally, the Leukemia and Lymphoma Society, Cancer Information Counseling Line, Kids Health have no information on late effects. Limited psychological and emotional late effect information is provided in the following websites: CureSearch, Ulman Foundation, American Childhood Cancer Organization, Cancer.net, and Cancer.org. Additionally, Cure-Search, OncoLink, American Childhood Cancer Organization (Candlelighters), Cancer Information Counseling Line, and Cancer.net offer support group resources. However, these support groups are not specifically for pediatric cancer survivors, apart from the National Children's Cancer Society.

Program evaluation
Individuals visiting the LEAP 3 AHEAD website will have the opportunity to provide feedback using a short, voluntary, pop-up survey where information will be collected about relevant demographics, how the individual discovered this website, and if the information was helpful.
The primary outcomes of interest to assess the impact of the program include (but are not limited to) the following: i) Who is using the website (e.g., public, cancer patients, family members, professionals), ii) Their demographics (e.g., age, race, ethnic background, gender, formal education level, occupation, primary spoken language, use of English or translated version of the website, place of residence, and health status); iii) Perceptions about the ease of use and content of the website; iv) If they will return to the website and reason(s), particularly for recognition of late effects or treatment protocols; and v) If they will refer somebody to the web site. Each of these questions will be examined by overall and racial/ethnic sub group where appropriate.
If the person is a patient/parent, they will be queried about whether the website information: i) assisted them in accessing medical or psychological treatments, ii) resulted in them practicing any of the preventive options; and iii) increased their awareness about opportunities (e.g., camps, dog companionship). In addition, website usage statistics will also be examined. Of particular interest is an evaluation of which content is viewed most frequently and where appropriate, tagged, re-posted or emailed to Facebook or to other friends.

Discussion
Currently, there are 15 websites that contain some information on late effects. For example, CureSearch has a section, "After Treatment" which discusses various physical complications and side effects of cancer treatment. Children's Oncology Group has a description of only the medical aspects of late effects associated with heart, dental, endocrine, GI, immune, neurological, pulmonary and reproductive systems. The National Children's Cancer Society has a resource where cancer survivors can input information on their own personal cancer diagnosis and receive information on possible late effects specific to them. Late effects are not the sole focus of any of the websites.
Coping with late effects throughout survivorship requires young survivors to continuously appraise their cancer's threat and its potential for change at various times throughout the remainder of their life [12], including negative effects on reproduction, re-interacting with friends or family members and formulating meaningful relationships, adjusting to changes in self-esteem and physical capabilities, and fearing a recurrence or second diagnosis of cancer [12]. LEAP 3 AHEAD addresses all these challenges within the context of the life course. For example, during critical periods of youth, tween, young adulthood, and adulthood, disruptions with peers and school may occur. A 17-year old survivors' sense of well-being may be founded on an ability to establish independence in life or perform well in school, whereas achieving expected life goals such getting married or having children may have greater salience for a 30-year old survivor's well-being [12].
Hence, this website is the first to provide age specific, audience specific, and language specific (bilingual) information to: a) assist childhood cancer survivors, families and their caregivers, and the public about the timely recognition of late effects and medical, emotional, neurocognitive, and psychological signs/symptoms and prevention strategies throughout the lifespan, and b) provide suggestions about how to reintegrate childhood cancer survivors socially with family and friends as well through education and employment prospects. At this point, the evaluation for reintegration has not occurred so it is unclear whether these suggestions will have an impact on childhood cancer survivors.
Nevertheless, it is problematic for childhood cancer survivors to reintegrate socially when they return back to school. Long absences and missed work could result in students feeling unprepared. Moreover, children may experience physical changes (e.g., amputation, hair loss) [13], feel depressed, anxious, rejected by their pears, and isolated. Teachers may lack knowledge about cancer, have unrealistic expectations, and may be unprepared to handle classmates' reactions [13]. Finally, parents may be fearful about sending their children back to school because of concerns about infection, medical emergencies [14], teasing by other children, and over-protectiveness.
The following examples from the website consist of social interactions for Friends-children until age 10, and School-children until age 10.
Regular follow-up care by health professionals who are trained to recognize and treat medical and psychological late effects is also extremely important for the long-term health of childhood cancer survivors. Hence, pediatricians, family physicians, psychosocial providers and internists may utilize this web-based resource within their practices and refer patients to LEAP 3 AHEAD.
Furthermore, childhood cancer survivors may gravitate towards risk-taking behaviors [15]. LEAP 3 AHEAD has a prevention section which educates survivors about indulging in healthy lifestyles (i.e., healthy diet, exercise, regular medical and dental checkups), while avoiding tobacco, alcohol and illicit drug use, and exposure to sunlight.

Conclusion
By 2020, an estimated 500,000 survivors of childhood cancer are expected to be living in the U. S [16][17]. Decisions made by doctors and parents could impact these children throughout their lifespan. Currently, in order for survivors to partake in childhood cancer survivorship programs they must have survived at least 2 years to 5 years since completion of all cancer therapy. If this criteria is met, then participants receive only yearly evaluations by a team of professionals specializing in cancer including, but not limited to, a psychologist, physician, nurse practitioner, and dietician. Because of the paucity of survivorship clinics nationally, strict criteria excluding entry directly after completion of treatment, and limited follow-up (annually), it is advisable to offer other complementary modalities to childhood cancer survivors. Furthermore, lower risk childhood cancer survivors are often transitioned back to their primary care physicians to continue lifelong follow-up. Often, adult -focused primary care providers lack survivorship expertise due to the paucity of survivorship-related content in medical school curricula and residency training.
To date, LEAP 3 AHEAD is the first national website to provide a comprehensive, accessible, affordable, and multi-dimensional approach about late effects for pediatricians, internists, nurse practitioners, psychologists, childhood cancer survivors and their families, as well as the public. This website could be of value to childhood cancer survivors and providers. LEAP 3 AHEAD evaluation is in its beginning; thus, information on its effectiveness and impact will be provided in future reports.
Supporting information S1 Graphic. Friends-children, school-children (until age 10). Important considerations and helpful solutions regarding friends and school, for children until age 10. (DOCX)