Original Article
Active Therapy and Models of Care for Adolescents and Young Adults With Cancer* Raveena Ramphal, MB, ChB1; Ralph Meyer, MD2; Brent Schacter, MD3; Paul Rogers, MD4; and Ross Pinkerton, MB, ChB, MD5
The reduction in the cancer mortality rate in adolescents and young adults (AYA) with cancer has lagged behind the reduction noted in children and older adults. Studies investigating reasons for this are limited but causes appear to be multifactorial. Host factors such as developmental stage, compliance, and tolerance to therapy; provider factors such as lack of awareness of cancer in AYA and referral patterns; differences in disease biology and treatment strategies; low accrual onto clinical trials; and lack of psychosocial support and education programs for AYA all likely play a role. Recommendations for change from a recent international workshop include education of physicians and patients concerning AYA cancer, improved cooperation between pediatric and adult centers, age-appropriate psychosocial support services, programs to help AYA with issues relevant to them, dedicated AYA hospital space, improved accrual to clinical trials, the use of technology to educate patients and enhance communication between patients and the health care team, and ensuring that resident and fellowship training programs provide adequate education in AYA oncology. The longer term goal is to develop AYA oncology into a distinct subspecialist discipline within oncology. The ideal model of care would incorporate medical care, psychosocial support services, and a physical environment that are age-appropriate. When this is not feasible, the development of ‘‘virtual units’’ connecting patients to the health care team or a combination of physical and virtual models are alternative options. The assessment of outcome measures is necessary to determine whether the interventions implemented result in improved surC 2011 American Cancer vival and better quality of life, and are cost-effective. Cancer 2011;117(10 suppl):2316–22. V Society. KEYWORDS: adolescents, young adults, neoplasms, health care delivery, oncology service, hospital.
Adolescents and young adults (AYA) with cancer are a distinct subgroup of patients within oncology. From the onset of symptoms until the completion of active therapy and beyond, the particular challenges they face have long been overlooked and underestimated. The reduction in the cancer mortality rate in this group has lagged behind the reduction noted in children and older adults.1 As a result, the relatively better prognosis that AYA with cancer had a quarter of a century ago compared with children has now been lost. The current 5-year survival rate in Canadian AYA is similar to that in children.2 Active Care Issues in AYA Compared with younger patients, AYA have a greater delay between the onset of symptoms and diagnosis.3 Possible reasons for this are the developmental stage of AYA, a time when they are more likely to believe themselves invincible. At a stage in life during which body image is paramount, they may delay presentation because of denial or embarrassment. They are transitioning to greater autonomy and may wish to have less parental supervision. They are often preoccupied Corresponding author: Raveena Ramphal, MB, ChB, Division of Hematology/Oncology, Children’s Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON Canada K1H 8L1; Fax: (613) 738-4828;
[email protected] 1 Division of Hematology/Oncology, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada; 2Cancer Clinical Trials Division, Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada; 3Department of Hematology and Medical Oncology, CancerCare Manitoba, Winnipeg, Manitoba, Canada; 4Division of Paediatric Hematology/Oncology, BC Children’s Hospital, Vancouver, British Columbia, Canada; 5Division of Pediatric Oncology, Queensland Children’s Cancer Centre, Royal Children’s Hospital, Hetston, Queensland, Australia
The articles in this supplement represent presentations and discussions at the ‘‘International Workshop on Adolescents and Young Adults with Cancer: Towards Better Outcomes in Canada’’ that was held in Toronto, Ontario, March 11-13, 2010. *Workshop on Adolescents and Young Adults with Cancer: Towards Better Outcomes in Canada, Supplement to Cancer. DOI: 10.1002/cncr.26048, Received: September 20, 2010; Revised: November 26, 2010; Accepted: November 29, 2010, Published online April 27, 2011 in Wiley Online Library (wileyonlinelibrary.com)
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with new life challenges such as increased educational, work, and family demands and new relationships. They are frequently less financially secure and less likely than older adults to be receiving routine medical care or to have medical insurance (a greater problem in countries without nationalized health care).4,5 Treatment delays also occur because physicians who have initial contact with AYA may be less familiar with the symptoms and signs of cancer in AYA and less likely to consider cancer as a possible diagnosis in a patient so young. The results of limited studies regarding whether delay in diagnosis has an impact on health outcomes have been inconclusive.6,7 Given that AYA cancer care is splintered between pediatric and adult oncologists, the referral pattern from the many different medical professionals who are the initial contact (primary care physicians, emergency room physicians, gynecologists, dermatologists, surgeons, etc) is often based on physician preference or familiarity with a specific referral institution. From the limited number of studies conducted on this subject, patient age and diagnosis appear to be important considerations for the referring physician. For adolescents, a patient with a diagnosis of leukemia appears to be referred more frequently to a pediatric center whereas those with carcinomas, lymphoma, and germ cell and other solid tumors are referred more often to adult centers.8-10 With regard to age, studies in Canada and the state of Utah in the United States have demonstrated that approximately one-third of patients ages 15 to 19 years are treated at pediatric centers.8,9 In the Canadian study, adolescents treated in an adult oncology center were found to be significantly older at the time of diagnosis compared with those treated in a pediatric oncology center (median age, 17.4 years vs 16.5 years).9 Whether other important factors are considered by the referring physician is unclear; these include a patient’s level of maturity; the promptness with which the patient is likely to be assessed at the referral center; whether there is access to clinical trial participation; and the level of support that the referral center is able to provide for educational, occupational, financial, and psychosocial needs. In 1 Canadian study, the median number of days between the onset of symptoms and first health care contact was significantly longer at adult centers compared with pediatric centers (92 days vs 57 days).9 In a study surveying adult oncologists who were members of the Association of Community Cancer Centers in the United States, once an adoles-
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cent was referred to an adult institution, subsequent transfer of care to a pediatric institution rarely occurred.11 The main reasons identified by the study were that adult oncologists appear to regard patients ages 16 to 21 years as adults and are comfortable treating the specific cancer or because of patient/family preference. Hospital age restrictions and other institutional barriers may also dictate referral patterns. In both pediatric and adult institutions, there is often a lack of awareness or focus on the many unique psychosocial issues AYA face and how this impacts compliance, adherence to therapy, and quality of life. A national Canadian survey (unpublished data) revealed that only a small number of both pediatric and adult centers had psychosocial support staff (such as social workers, psychologists, and psychiatrists) who had special expertise or interest in AYA. The results of the study also indicated that very few centers had resources such as peer mentoring, support groups, or counseling services dedicated to AYA. Given that AYA are going through a challenging developmental stage, exacerbated by having to deal with a life-threatening illness, focused age-appropriate psychosocial support would be beneficial in many cases. Data from the same national Canadian survey found that very few pediatric and adult centers have programs that assist AYA with important issues such as education, fertility, establishing financial independence, or navigation of the health care system and only a minority of centers provided inpatient and outpatient space reserved for AYA patients. This means that AYA are surrounded by patients much older or younger than themselves, which increases their sense of isolation and reinforces their perception that they are different from their peers. In most pediatric or adult oncology training programs, there is a lack of education and focus on AYA, which likely reduces an oncologist’s ability to understand AYA issues. Several courses in adolescent medicine are in place or currently under development, including some Internet-based programs. One such course is the Coventry University (Coventry, United Kingdom) course ‘‘Contemporary Health Care - Cancer Care for Teenagers and Young Adults,’’ which is an international World Wide Web-based course for health or social care professionals aimed at preparing students for advanced level practice in cancer care for AYA. However, adolescent medicine courses may not deal adequately with cancer-specific issues and, conversely, oncology courses that include modules on AYA may have insufficient depth with regard to adolescent medicine. It may also be difficult to design
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courses that meet the broad multidisciplinary needs of medical, nursing, and allied health disciplines. Participation of AYA in either pediatric or adult clinical trials is low. This may partially explain why, in many countries, survival among adolescents is improving at a slower rate than in children and older adults. The Canadian Childhood Cancer Surveillance and Control Program estimates that only 10% to 20% of adolescents with cancer participate in clinical trials in Canada.9 The participation rate of young adults in the United States is even lower at < 2%, compared with 60% in children and 3% to 5% in older adults.12 To our knowledge, the reasons for this low accrual rate have not been well studied to date, but may include treatment of patients in centers that do not have open clinical trials, a lack of awareness by the treating physician of open trials, patients being unaware of or reluctant to participate in trials, age limits on open trials, fewer trials for tumors common to this age group, and a lack of collaboration between pediatric- and adultbased cooperative groups. For example, constraints or barriers to recruitment in adult units to Children’s Oncology Group (COG) trials may be because of a lack of formal site approval of the adult unit, even if there is close interaction between adult and pediatric centers and the age limit for the COG study extends well into the AYA range. Although the survival benefit to an individual participating in a clinical trial may be debated, there is no doubt that the knowledge and experience gained from clinical trials benefits future patients.13 There are many aspects of the AYA population that are understudied and require further research. These include age- related differences in tumor biology, late sequelae of therapy, and chemotherapy pharmacokinetics and pharmacodynamics. More refined and individualized dosing regimens may be required to allow for effective dose delivery in AYA. Compared with older and younger patients, AYA have a different prevalence and spectrum of malignancies, and even for the same tumors the disease biology is often different. In children, embryonal tumors such as Wilms tumor, neuroblastoma, and hepatoblastoma predominate, whereas in adults epithelial cancers such as breast, prostate, colon, and lung cancer are more common. This transition of cancer prevalence occurs over several decades, from adolescents through to young adulthood. For example, in leukemia, there is a trend away from the overwhelming acute lymphoblastic leukemia (ALL) predominance in childhood toward a more equal distribution of ALL and acute myeloid leukemia (AML) in the AYA population. Moreover, the biology of ALL in AYA
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changes to worse prognostic subtypes. For non-Hodgkin lymphoma, the subtype distribution changes with age from a predominance of lymphoblastic and Burkitt lymphomas during early childhood to a predominance of diffuse large cell lymphoma in AYA. The types of soft tissue sarcomas also differ considerably by age, changing from a predominance of rhabdomyosarcoma in childhood to nonrhabdomyosarcoma soft tissue sarcomas in adolescence. Furthermore, host factors such as compliance with and tolerance to therapy are generally worse in the AYA group compared with children. There are also differences between adult and pediatric institutions with regard to AYA treatment regimens for specific tumor types. For some cancers, outcomes for adolescents with cancer appear to be more favorable when treatment is provided in a pediatric compared with an adult oncology center.1417 Moreover, clinical trials offered in pediatric centers may be more appropriate for certain types of cancer in AYA than those offered at adult centers. For patients ages 16 to 20 years with ALL who are treated on concurrently conducted trials, the 7-year event- free survival rate was 63% for those treated on the pediatric Children’s Cancer Group study and 34% for those treated on the adult Cancer and Leukemia Group B regimen.18 During a similar period, the 5-year event-free survival rate for patients ages 15 to 18 years who were treated on the pediatric DanaFaber Cancer Institute ALL Consortium protocols was 78%.19 In France, patients ages 15 to 20 years who were treated on a pediatric ALL protocol had a 5-year eventfree survival rate of 67% compared with 41% for those treated on the adult protocol.20 The survival of adults with ALL also improved significantly after treatment derived from pediatric trials was introduced into the trials at The University of Texas MD Anderson Cancer Center.21 For non-Hodgkin lymphoma, data from 13 Surveillance, Epidemiology, and End Results registries indicated that young adults (those ages 20 to 29 years) had a significantly lower 5-year overall survival rate than children and adolescents (those ages birth to 19 years) (hazard ratio, 2.06; 95% confidence interval, 1.65-2.56). In Canada, a study comparing pediatric patients (median age, 13.4 years) with adult patients (median age, 26.1 years) with localized Ewing sarcoma who were treated on different regimens found significantly better 3-year event-free and overall survival rates in the pediatric group.22 Treatment outcomes are known to be worse in adults with Ewing sarcoma compared with children.23,24 However, adults are able to tolerate the more intensive Ewing sarcoma
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pediatric protocols and are able to achieve similar outcomes to children when treated on pediatric protocols.2527 Whether different treatment regimens, differences in disease biology in different age groups, or both accounted for the survival differences in some of these studies is unclear. More recently, collaboration between pediatric and adult cooperative groups both in the United States and Europe (eg, the Southwest Oncology Group opening the COG trial for metastatic Ewing sarcoma to adult patients) will help clarify the role of biology versus treatment with regard to differences in outcome. Conversely, there is good evidence that AYA with adult-type cancers fare better at adult institutions, possibly because of adult oncologists having more familiarity and greater expertise with these tumors.28 Survival alone may not be the only significant endpoint. In AML, there have been significant improvements in survival noted in AYA, in part because of the use of allogeneic bone marrow transplantation (BMT) procedures. It is possible that, in certain risk groups, the inevitable risks of acute and late morbidity of such procedures may not be necessary, as has been demonstrated in children.29 The same has been shown to apply to the role of allogeneic BMT in AYA with ALL.30 Recommendations for Change To address the issues outlined above, an international workshop entitled ‘‘Adolescents and Young Adults with Cancer: Towards Better Outcomes in Canada’’ was convened in Toronto, Ontario, Canada. This workshop brought together health professionals from pediatric and adult oncology, as well as former AYA cancer patients. The following is a synopsis of the key issues discussed. It should be noted that there are currently limited data with regard to the benefit of implementing some of the measures outlined below, but many of the recommendations come from established experts in the field. Moreover, data obtained before and after the implementation of these measures can be compared and will provide a useful source of information for future research. The following recommendations, with the most important listed first, may help to improve survival and quality of life in AYA with cancer.
•
Improve accrual onto clinical trials. Combine pediatric and adult clinical trials with removal of ‘‘artificial’’ age restrictions to improve accrual. Increase collaboration between pediatric and adult cooperative groups, includ-
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•
•
•
•
ing large intergroup trials. Explore mechanisms to facilitate enrollment from adult centers into pediatric trials and vice versa. Recognize contributions of peer-reviewed research facilities and satellite centers. Provide access to a single comprehensive registry to track outcome of trials in relation to treatment and location of treatment. Improve communication, collaboration, and cooperation between adult and pediatric centers. Introduce more flexible institutional policies to ensure more efficient patient transfer. Create joint clinical and educational meetings, shared AYA clinics, and shared resources. Educate physicians and patients about factors to consider to ensure referral to the center best equipped to deal with the patient’s needs. Support programs to educate trainees about the unique needs of AYA (eg, reciprocal rotations of resident and fellowship trainees between pediatric and adult centers). Stimulate research in AYA oncology by mentoring trainees to develop a focused interest in AYA care. Educate primary health care workers about AYA cancer. Increase awareness of the signs and symptoms of AYA cancer. Develop programs/resources to facilitate referrals to cancer programs to reduce the referral time. Enhance supportive care services and resources for AYA cancer patients. Provide specific programs and services to help with AYA issues (education, finance, sexuality, fertility preservation, peer support, psychosocial support, etc.). Develop programs to encourage multidisciplinary care teams to focus on the medical and psychosocial issues of AYA. Reorganize staff duties to allow certain staff to develop a focus and interest in AYA patients. Optimize the clinical environment. Provide dedicated AYA space to encourage AYA to socialize with their cancer peers. Supply World Wide Web-based programs featuring information regarding cancer and cancer-related health risks, and World Wide Web-based psychosocial programs to extend support beyond the clinical care environment.
Models of Care Table 1 outlines the features of the ideal model of care. When the ideal model is not feasible because of geographic, economic, political, or other reasons, tradeoffs may be necessary. If the maximum level of support is not available in all 3 domains (quality subspecialty medical care, psychosocial support services, and ideal physical environment), new resources may need to be focused initially on one area or another. Access to medical expertise
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Original Article Table 1. Features of the Ideal Model of Care
Table 2. Barriers to Change
The ideal model proposed would incorporate the 3 domains of a quality subspecialty: medical care, psychosocial support services, and an appropriate physical environment. It would include, but not be restricted to, the following features: Expert medical care for the full spectrum of cancer that affects this age group. This would involve access to domains and tumor groupspecific expertise that could be either pediatric or adult medical/radiation oncologists. Access to clinical trials and dedicated research strategies. Enhanced psychosocial support by a multidisciplinary team trained to work with patients at this developmental stage. A physical environment, both inpatient and outpatient, that is age appropriate and patient friendly. Access of patients to education and information regarding the cancer type affecting them, as well as the acute and late effects of treatment. The use of technology to enhance communication between patients and the health care team, between individual members of the health care and psychosocial teams, and between patients themselves. The model chosen should be accessible, affordable, available, and patient friendly.
Barriers to change include but are not limited to: Lack of awareness by primary health care providers, the public, administrators, and politicians of the prevalence of AYA cancer and its longterm consequences. The top-down approach of many health organizations, which makes it difficult to implement change. Health authorities are not well educated regarding the basic needs of patients in this age group. Lack of communication between pediatric and adult oncologists who may both be responsible for the management of patients in this age group. Lack of funding and resources to develop appropriate programs. Lack of involvement of the patient cohort. Geographical challenges such as distance from the treatment center.
for a specific cancer is generally recognized as the first priority. The development of ‘‘virtual units’’ that use technology to connect patients to medical experts and multidisciplinary teams or a combination of physical and virtual models may be alternative options. Using the basic elements, each geographic area can develop a system that works best for them. Many of the recommendations can be implemented, often at minimal cost, at a local level. Examples include opening pediatric trials in adult centers and vice versa (when eligibility criteria allow); increasing communication and collaboration between local pediatric and adult centers; creating joint AYA meetings, clinics, and shared resources between pediatric and adult centers; implementing specific AYA supportive care programs; and focusing the efforts of multidisciplinary teams on addressing AYA psychosocial issues and creating World Wide Web-based programs for AYA. Other recommendations may require assistance in terms of funding and support at a provincial, state, or national level. Examples include providing AYA dedicated space, which may require physical restructuring; changing the curriculum for trainees to include more AYA oncology training; and educating health care workers concerning the signs and symptoms of cancer in AYA and guidelines regarding referral. Barriers to Change Table 2 outlines some of the barriers to change. The following are suggestions as to how these barriers may be
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Abbreviations: AYA, adolescents and young adults.
overcome. Education of primary health care providers, the public, health authorities, and politicians regarding the prevalence of AYA cancer, its long-term consequences, and the benefits of early recognition and treatment is needed. The assistance of advocacy groups to spread this message and help with fundraising for specific AYA oncology initiatives has proved invaluable in countries such as the United States and the United Kingdom. Better communication at a local level between pediatric and adult oncologists can be achieved by ensuring more opportunities for contact between these 2 groups. Combined AYA clinics, education sessions, conferences, clinical trials, and multidisciplinary team meetings as well as reciprocal rotations of resident and fellowship trainees between pediatric and adult centers all help to improve communication and nurture professional relationships. Inviting current and former patients to participate in conferences, fundraising, and educational events so that their voices are heard will help to encourage involvement by the patient cohort. Geographical challenges such as distance from the treatment center can be attenuated through the use of technology such as Web sites, teleconferences, and video links for both educational purposes and to provide expert advice to local physicians. Conclusions To obtain public, political, and financial backing, it is important to justify the need for change and to have ongoing evaluation to demonstrate that these changes make a difference. Outcome measures should be defined and quantified. Comparison of outcome measures before and after implementation of an intervention could include changes in health-related quality of life, recurrence-free and overall survival, patient satisfaction, lag time from symptoms to
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diagnosis, productivity levels, and levels of AYA oncology research activities and collaboration. Health economics should also be included to demonstrate that the potential benefits are worth the cost.
11. 12.
FUNDING SOURCES Funding for the workshop was provided by C17; the Advisory Board of the Institute for Cancer Research at the Canadian Institutes for Health Research (CIHR); the Public Health Agency of Canada; the Ontario Institute for Cancer Research; the Meetings, Planning and Dissemination Grants program of the CIHR; the Terry Fox Research Institute; LIVESTRONG, formerly the Lance Armstrong Foundation; the Canadian Cancer Society Research Institute; Young Adult Cancer Canada; Hope and Cope; and the Comprehensive Cancer Centre at the Hospital for Sick Children, Toronto, in addition to the support provided by the Canadian Partnership Against Cancer to the Task Force on AYA Cancer.
13.
14. 15. 16.
CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures.
17.
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