Adolescents' and Young Adults' Adherence to Medication During the Transition to Adult Healthcare: A Developmentally Appropriate Framework for Optimising Adherence-Promoting Interventions.

Defining the Genomic Make up of Acute Myeloid Leukemia in Adolescents and Young Adults (AYA): Report from COG AAML03P1, AAML531 and SWOG S0106

Adolescents and Young Adults (AYA) with Myeloproliferative Neoplasms (MPNs): Analysis of Patient Outcomes and Impact of High-Molecular Risk Mutations

Patterns of Care and Outcomes in Adolescents and Young Adults with Myeloproliferative Neoplasms: A Multicenter Population-Based Study

The development of adolescent and young adult (AYA) oncology as a burgeoning discipline that is now into its own adolescence may be best illustrated by the surge in AYA oncology publications in peer-reviewed journals during the past three years. Prior to 2007, the number of articles identified by the search term ‘‘adolescents young adults cancer’’ in the PubMed database ranged from 129 to 381 per year. Since then, the number increased to 598 in 2007, 1971 in 2008, and 4045 in 2009. The dramatic increase is still well short of the 7000–7500 articles per year that the ‘‘children cancer’’ search term identifies, especially when one considers that the number of cancer patients in the AYA age group is four to six times greater, depending on what age range is used for the AYA group. Nonetheless, the change in publication rate of AYA cancer reports and reviews is striking testimony of need and partial success. To understand the history that led to this revolution, several of its pioneers in England, the United States, and Canada were convened for a roundtable discussion to offer their recall. As described below, the original seed appears to have been sowed in England, thanks to Ian Lewis and London’s Teenage Cancer Trust. A root took hold a decade later when national statistics in the United States showed a survival progress gap that was analogized to the famous London Tube gap between the platform and the Underground train. The stems that then broke ground were conferences, organizations, hospital and outpatient programs, scientific reviews, and international collaborations. The participants in this Roundtable undoubtedly neglected many other events along the way, but they are all appreciative of the emerging buds and blossoms of AYA oncology. Most of all, they sense that AYAs around the world will ultimately truly benefit in improved prevention, early detection, and treatment of cancer during the prime of their lives.

Approaches to Increasing Clinical Trial Access and Enrollment for Adolescents and Young Adults with Cancer.

Cancer survival among adolescents and young adults (AYAs) was previously reported as showing little or no improvement compared to younger or older counterparts. The role of the HIV/AIDS epidemic in the AYA survival deficit has not been evaluated. Using cancer registry data from the Surveillance, Epidemiology, and End Results program (SEER 9), we examined sex-specific 5-year relative survival trends for children (0-14 years old), AYAs (15-39 years old), and older adults (40 years and older) diagnosed with cancer during 1973-2009 and followed through the end of 2014. The analysis was conducted with and without Kaposi sarcoma (KS) and lymphomas, and by two time periods: 1973-1977 (before the human immunodeficiency virus/acquired immunodeficiency syndrome [HIV/AIDS] epidemic) and 2005-2009 (after the HIV/AIDS epidemic waned). A total of 3 209 721 invasive cancer cases were included in the study (27 646 children, 213 930 AYAs, and 2 968 145 older adults; 24 803 children, 178 741 AYAs, and 2 844 062 older adults when KS and lymphoma cases were excluded). We found that 5-year relative survival for AYAs exceeded that of children and older adults before the onset of the HIV/AIDS epidemic (eg, during 1973-1979, 0.58-0.67 among male AYAs as compared with 0.47-0.61 for male children and 0.36-0.42 for male older adults; among female AYAs, the numbers were 0.73-0.77 as compared with 0.51-0.65 for female children and 0.52-0.55 for female older adults); substantially declined during 1983-1997 when HIV/AIDS lacked effective treatment among male AYAs; and returned to be higher than most age groups by the late 1990s after HIV/AIDS was controlled. Nonetheless, comparison of survival improvement between 1973-1977 and 2005-2009 demonstrated less progress in AYAs than other age groups, which was due to AYAs' better baseline survival and larger survival gains among children and older adults in recent years. Apart from the temporary impact of HIV/AIDS, survival among AYA cancer patients has shown sustained improvement and superiority relative to other age groups. However, these encouraging findings do not negate the distinctive challenges in cancer diagnosis, treatment, and survivorship faced by AYAs.

Lymphoma is a common malignancy among adolescents and young adults (AYAs) which is generally defined as 15-39 years. Relative to other age groups, lymphoma in AYAs remains understudied with heterogeneous treatment options. We performed a retrospective review of patients aged 18-60 years in the Australasian Lymphoma and Related Diseases Registry (LaRDR) with new diagnoses of the common subtypes of lymphoma in AYAs between January 2016 and April 2023. The subtypes are classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and Burkitt lymphoma (BL). Patient demographics, disease characteristics, treatment and outcome data were collected, and comparisons were made between AYAs (18-39 years) and older adults (OAs) (aged 40-60). AYAs had higher rates of cHL and PMBCL whereas OAs presented more frequently with DLBCL. AYAs with cHL and PMBCL had higher rates of early-stage and low-risk disease than OAs. In contrast, both AYAs and OAs were more likely to present with advanced-stage DLBCL and BL. AYAs with cHL were more likely to be treated with BEACOPP as compared to OAs who were more commonly treated with ABVD. There was no significant difference in treatment regimens for DLBCL, PMBCL or BL between AYAs and OAs. AYAs with cHL had better overall survival (OS) compared to OAs; specifically, cHL AYAs had better OS and DLBCL AYAs had better progression-free survival (PFS) and OS compared to OAs. The study provides valuable data on patient and disease characteristics, treatments used and outcomes in AYA compared to OA aged 40-60 years. Registry data such as from LaRDR can help improve treatment standardisation and AYA patient outcomes. The authors have confirmed clinical trial registration is not needed for this submission.

Background: Five-year survival rates for those diagnosed with soft tissue sarcoma (STS) have improved significantly among children and older adults (OAs), but these same trends have not been observed for adolescents and young adults (AYAs). While these disparities could be due to differences in biology or treatment, few studies have evaluated STS occurrence and outcome in AYAs. Therefore, the purpose of this study was to evaluate differences between adolescents and young adults (AYAs) and older adults (OAs) diagnosed with STS by stratifying analysis by: (1) clinical presentation; (2) treatment; and (3) survival. Methods: Data were obtained from the Scandinavian Sarcoma Group (SSG) Central Register, which includes information on 5,747 patients from Sweden and Norway, diagnosed with a STS during 1986-2011. Variables included: age at diagnosis, metastasis at diagnosis, tumor size, histology, adjuvant treatment, date of death or last follow-up. AYAs were defined as those diagnosed ages 15-39 years. Categorical variables were analyzed using chi-square tests, and continuous variables were analyzed using t-tests. Overall survival (OS) and recurrence-free survival (RFS) were compared between AYAs and OAs using Kaplan-Meier estimates and log-rank tests. All analyses were conducted overall and by common STS subtypes. Results: Overall and by STS subtype, there were significant differences between AYAs and OAs on presentation, treatment, and survival. The distribution of STS subtypes was different between OAs and AYAs. For example, OAs were more likely to be diagnosed with leiomyosarcoma compared to AYAs (18% vs. 10%, p<0.001), whereas AYAs were more likely to be diagnosed with malignant peripheral nerve sheath tumor (MPNST, 9% vs. 4%, p<0.001). OAs were also more likely to have larger tumors (>5 cm, 67% vs. 52%, p<0.001) and higher malignancy grade (grade IV, 45% vs. 31%, p<0.001). Interestingly, AYAs were more likely to be treated with radiotherapy and chemotherapy compared to OAs (12% vs. 5%, p<0.001). There were also differences within STS subtypes. For example, OAs were more likely to have metastasis compared to AYAs if diagnosed with leiomyosarcoma (18% vs. 10%, p=0.04). In most scenarios AYAs had significantly better OS and RFS compared to OAs, other than for MPNST (OS: p=0.19, RFS: p=0.28). Conclusions: There were several differences between AYAs and OAs on STS presentation, treatment, and outcome. AYAs not only had differences in terms of STS subtypes but also tumor size and malignancy grade within subtypes. Additional work is needed to characterize the biology underlying these differences, which will inform future treatment strategies for both AYAs and OAs with STS. Citation Format: Vidal M. Arroyo, Philip J. Lupo, Beatrice Melin, Emelie Styring, Olga Zaikova, Karin Papworth. Soft tissue sarcoma clinical presentation, treatment, and survival in adolescents and young adults compared to older adults: A report from the Scandinavian Sarcoma Group [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1197.

Cancers in adolescents and young adults (AYAs) (age 15-39 years) often present with unique characteristics and poor outcomes. To date, spinal cord glioblastoma, a rare tumor, remains poorly understood across all age groups, including AYAs. This comparative study aimed to investigate the clinical characteristics and outcomes of spinal cord glioblastoma in AYAs and older adults (age 40-74 years), given the limited availability of studies focusing on AYAs. Data from the Neurospinal Society of Japan's retrospective intramedullary tumor registry (2009-2020) were analyzed. Patients were dichotomized on the basis of age into AYAs and older adults. Univariate and multivariate Cox proportional hazards regression models were utilized to explore risk factors for overall survival (OS). A total of 32 patients were included in the study, with a median (range) age of 43 (15-74) years. Of these, 14 (43.8%) were AYAs and 18 (56.2%) were older adults. The median OS was 11.0 months in AYAs and 32.0 months in older adults, and the 1-year OS rates were 42.9% and 66.7%, respectively, with AYAs having a significantly worse prognosis (p = 0.017). AYAs had worse preoperative Karnofsky Performance Status (KPS) than older patients (p = 0.037). Furthermore, AYAs had larger intramedullary tumors on admission (p = 0.027) and a significantly higher frequency of intracranial dissemination during the clinical course (p = 0.048). However, there were no significant differences in the degrees of surgical removal or postoperative radiochemotherapy between groups. The Cox proportional hazards regression model showed that AYAs (HR 3.53, 95% CI 1.17-10.64), intracranial dissemination (HR 4.30, 95% CI 1.29-14.36), and no radiation therapy (HR 57.34, 95% CI 6.73-488.39) were risk factors for mortality for patients of all ages. Worse preoperative KPS did not predict mortality in AYAs but did in older adults. The high incidence of intracranial dissemination may play an important role in the poor prognosis of AYAs, but further studies are needed. The clinical characteristics of AYAs with spinal cord glioblastoma differ from those of older adults. The prognosis of AYAs was clearly worse than that of older adults. The devastating clinical course of spinal glioblastoma in AYAs was in line with those of other cancers in this age group.

Recognizing a current lack of knowledge and effective treatments for adolescents and young adults who are diagnosed with cancer, leaders in the field have launched efforts to address the problem. “Historically, adolescents and young adults have not participated in clinical trials to the same degree as younger children and older adults, yet their cancers are also somewhat different from what we see in these other populations,” says Victor Santana, MD, vice president of clinical trials administration at St. Jude Children's Research Hospital in Memphis, Tennessee, where children and young adults aged up to 21 years receive medical care. Patients with cancer who first are diagnosed between 15 and 39 years of age are considered to be the adolescent and young adult (AYA) population. The reasons for the lower clinical trial participation rates noted among this age group vary, but include the lack of health insurance among many younger adults, particularly those in their 20s, and the fact that a good number of these patients may be seen by community physicians who do not routinely participate in clinical trials. In contrast, note Dr. Santana and other experts, the majority of pediatric patients are treated at academic medical centers that regularly enroll them in clinical trials. For example, at St. Jude, all patients are offered clinical genomic testing of their tumors, and the hospital's patients aged 25 years and younger can be enrolled in clinical trials depending on their specific disease. Responding to this and other disparities, the American Society of Clinical Oncology (ASCO) recently published new guidelines to modernize clinical trial eligibility criteria.1 These guidelines recommend lowering the enrollment age for laterphase trials in diseases that span adult and pediatric populations from 18 to 12 years. The new recommendations are the result of efforts by a working group that included representation from ASCO, Friends of Cancer Research, and the US Food and Drug Administration (FDA). In addition, the US Congress recently approved the reauthorization of 2 laws that are designed to stimulate the development of new drugs for children: the Best Pharmaceuticals for Children Act, which is considered “the carrot” because it provides incentives for drug development in this area, and the Pediatric Research Equity Act, which requires drug companies to comply, and is considered “the stick,” explains Richard Schilsky, MD, chief medical officer of ASCO. Ensuring that ASCO “walk the talk” of its new recommendations, the organization recently lowered the enrollment age of its Targeted Agent and Profiling Utilization Registry (TAPUR) Study from 18 years to 12 years. A basket clinical trial that attempts to learn from the way physicians are applying precision medicine in oncology practice, TAPUR is open to patients with advanced cancer who have undergone genomic profiling of their tumors, and gives patients access to 19 different targeted cancer therapies that already have been approved by the FDA for other indications. Among these are 11 drugs with an established pediatric dose and which would be made available to adolescent patients whose tumors have one of the mutations that are required for patients to be enrolled on the study, says Dr. Schilsky. He adds, “We're seeing a recognition that certainly for children ages 12 and up, they are more physiologically similar to adults than to children, and therefore it is likely to be safe to administer drugs in doses close to those used in adults.” Actually enrolling younger patients on TAPUR is complicated, which is why ASCO leaders have reached out for help. They are working with 2 pediatric oncologists, one in Boston and one in Chicago, to identify large centers around the country that conduct a significant amount of pediatric genomic profiling in order to recruit these patients. “My hope is that by the middle of 2018, we'll start to see some younger patients being enrolled on the study,” Dr. Schilsky says. Noting the need for more research into precision medicine for all pediatric cancers, the National Cancer Institute (NCI) and Children's Oncology Group launched Pediatric MATCH, a nationwide cancer treatment clinical trial for children and adolescents aged 1 to 21 years. This study is modeled after the NCI adult MATCH trial. In the study, patients with solid tumors that are not responding to treatment are assigned to an experimental treatment based on their tumor's genetic mutations. The plan is to screen the tumors of 200 to 300 pediatric patients each year until 1000 have been screened. —Nita Seibel, MD “We hope we'll learn so much more about the biology of tumors that occur in both children and adolescents,” says Nita Seibel, MD, head of Pediatric Solid Tumor Therapeutics in the Clinical Investigations Branch of the Cancer Therapy and Evaluation Program at the NCI. “We also will be collecting germline blood samples to help determine if the tumors were caused by something hereditary.” Currently, there are 8 different treatment arms in the study, with 2 more in development, and the study is expected to run for approximately 3 to 4 years. Researchers want to enroll 20 patients per treatment arm. If at least 3 patients experience tumor shrinkage with a drug, more patients can be added to that arm, she says. Dr. Seibel says that one key question regarding cancers diagnosed in AYA patients is whether and how they are different from the same cancers occurring in other populations. She cites the example of acute lymphoblastic leukemia, which has better outcomes in young children than in adolescents and young adults. Scientists studied tumor specimens from the AYA population and found a unique, Philadelphia chromosome-like genetic signature that is more difficult to treat with standard therapies for the disease. “We're now screening to see if we can identify patients with those mutations and combine newer drugs with standard chemotherapy to determine if we can improve outcomes,” she says. Other common cancers in the AYA population that have yielded good results include thyroid cancer and Hodgkin lymphoma. However, non-Hodgkin lymphoma and acute myeloid leukemia have not been as easy to treat in this age group, and researchers suspect there may be genetic differences in these tumors as well. Similarly, although breast and colon cancer are rarer in adolescents, both diseases tend to result in poorer outcomes among younger adult patients. Nevertheless, it has been difficult to obtain a large number of samples in this age group to study the differences in these tumors, Dr. Seibel notes. “We're not sure if these patients don't do as well because of the biology of the tumor or because they are not getting the most up-to-date treatment,” she says. In an effort to encourage more community oncologists to offer their patients the opportunity to enroll in clinical trials, the NCI has offered 2 workshops to help educate these physicians about the importance of doing so. Dr. Seibel projects that approximately 10% of the tumors screened in the Pediatric MATCH trial will have some type of genetic mutation that can be treated by a drug. The reason is because children do not usually have the same number of mutations in their tumors as adults do. Environmental factors often play more of a role in cancers occurring in adults, whereas tumors in children may have more of an inherited component, she says. Although some of the drugs in the study have never been tested in children, the FDA is allowing them to be included because they have demonstrated safety in phase 2 studies with adults, Dr. Seibel says. She adds that the pediatric dosages will start out lower than adult dosages of these drugs. Both the Pediatric MATCH trial and TAPUR will gather data that could help scientists better understand these “differences in the footprints of tumors across the age spectrum,” Dr. Santana says. At St. Jude, patients are examined “holistically,” says Dr. Santana, and are followed into adulthood through the hospital's survivorship clinics, in which they may be offered the opportunity to enroll in survivorship clinical trials. Moreover, St. Jude provides separate clinic hours, locations, and support for AYA patients, who often feel quite distinct from their younger counterparts, he notes. Researchers are examining ways to reduce treatment toxicity in patients with Hodgkin lymphoma, many of whom are adolescents and young adults, Dr. Santana reports. He notes that, although patients may be cured of the disease, the chemotherapy and radiotherapy administered for it, including anthracyclines and alkylates, can lead to long-term heart problems, reproductive system challenges, and second malignancies. Recently, St. Jude's participated in clinical trials that helped lead to FDA approval of brentuximab, a new targeted agent for Hodgkin lymphoma, with the goal of reducing treatment toxicity in patients. The drug is an antibody that is directed against one of the antigens in the tumor cell and therefore is less likely to produce as many toxic side effects, he notes. It's a good idea that these programs are taking adolescents and young adults seriously,” says Dr. Santana. “And, hopefully, they will address some of the barriers to research in this area.”

371 Background: Identity development is the process that informs how an individual views oneself and develops a sense of self. A cancer diagnosis during adolescence and young adulthood (AYA; ages 15-39) disrupts AYAs’ identity development and creates identity distress. Identity development is a key developmental task during AYA. It is a recognized psychosocial concern and need for diagnosed AYAs but remains an understudied psychosocial need in AYA oncology care. Identity development can be promoted (or inhibited) in AYAs’ social interactions. AYAs’ communication with parents (often their primary source of support) may function adaptively or maladaptively for AYAs’ identity development. A communication skills intervention for diagnosed AYAs and parents could address communication strategies that promote AYAs’ healthy identity development while buffering identity distress. To capture knowledge that will contribute to a communication skill intervention, this study aimed to identify parent – AYA communication that promotes or inhibits identity formation. Methods: We recruited 14 AYAs to participate in audio-recorded, semi-structured, in-depth interviews. Eligibility criteria for AYAs included: 1) must be diagnosed with any type of cancer during adolescence (aged 15-18) or emerging adulthood (aged 19-29) and 2) be in active treatment or up to 32 months since the end of treatment. Interviews were thematically analyzed using constant comparative method. Results: AYAs’ age ranged from 19-29 ( M =24 years old), and their age of diagnosis ranged from 15-27 years ( M =21 years old). Diagnosed AYAs shared four types of identity disruptions that involved communication with their parents: independence, friendships, sexual orientation/behavior, and long-term goals. They also shared how parents’ communication either promoted identity development or contributed to identity distress. Results indicated that parents’ using parental psychological control in communication contributed to AYAs’ identity distress. AYAs shared parents prioritizing the AYA’s voice and engaging in emotionally supportive communication fostered their identity development. Conclusions: This study captures specific communication approaches and behaviors in parent-AYA communication and its promotion of AYAs’ identity development or contribution to identity distress. Findings demonstrate the importance of developing communication skills training and conversation tools to helps both AYAs and parents learn how to communicate to promote AYAs’ identity development and better overall psychological well-being.

Adolescent and Young Adult (AYA) Hematopoietic Cell Transplantation (HCT) Recipients Have Similar Quality of Life (QoL) Compared to Older Adults in the First Year Post-Transplantation

Cancer care and well-being in adolescents and young adults during the coronavirus disease 2019 pandemic: A UK sarcoma perspective.

SY15-02: Health insurance and outcome disparities in adolescents and young adults with cancer

Outcomes in Adolescents and Young Adults with Hodgkin Lymphoma Treated with and without Radiation Therapy On CCG 5942: A Report From the Children's Oncology Group