Karen Albritton

Assessing the health care needs of adolescent and young adult cancer patients and survivors

Improvements in cancer outcomes observed for the United States population as a whole are not experienced as such by adolescent and young adult (AYA) patients. The objective of this study was to identify important health and supportive care needs for AYA patients and survivors.

Challenges in the recruitment of adolescents and young adults to cancer clinical trials

The adolescent and young adult (AYA) oncology population has seen inferior progress in cancer survival compared with younger children and older adults over the past 25 years. Previously, AYAs had the best survival rates due to the prevalence of highly curable diseases including Hodgkin lymphoma and germ cell tumors, yet today AYAs have inferior survival rates to children and some adult cohorts. Survival rates are particularly poor for AYA‐specific diseases such as sarcomas. Research involving children and adults diagnosed with common malignancies such as acute lymphoblastic leukemia has resulted in improved survival rates. However, AYAs have not directly benefited from such research due to low rates of access to and accrual on clinical trials. AYAs are less likely to have insurance or access to healthcare, are more likely to see providers who are not part of research institutions, and are less likely to be referred to or to join clinical trials, all of which may contribute to worse outcomes. Few clinical trials target AYA‐specific diseases, leading to little information regarding how these diseases behave and what role the host plays. Tumor samples for this population are underrepresented in national tumor banks. Coupled with the need for more clinical trials that focus on AYA‐specific cancers, better collaboration between adult and pediatric cooperative groups as well as increased education among community oncologists and primary care providers will be needed to enhance participation in clinical trials with the goal to increase survival and improve quality of that survival. Cancer 2007.

Sunitinib Treatment in Pediatric Patients With Advanced GIST Following Failure of Imatinib

Sunitinib inhibits KIT and other members of the split‐kinase‐domain family of receptor tyrosine kinases. Sunitinib prolongs survival in adult patients with imatinib‐resistant gastrointestinal stromal tumor (GIST). We report the experience with sunitinib in pediatric patients with advanced GIST following failure of imatinib.

Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma.

Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose 153Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 ± 0.4 mCi; range, 0.67-1.8 mCi). All patients received autologous stem cell reinfusion 2 weeks after 153Sm to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11 of 11 patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m2) in combination with 153Sm-EDTMP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m2/d × 4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6- to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.

Unmet Support Service Needs and Health-Related Quality of Life among Adolescents and Young Adults with Cancer: The AYA HOPE Study.

Introduction: Cancer for adolescents and young adults (AYA) differs from younger and older patients; AYA face medical challenges while navigating social and developmental transitions. Research suggests that these patients are under or inadequately served by current support services, which may affect health-related quality of life (HRQOL). Methods: We examined unmet service needs and HRQOL in the National Cancer Institute’s Adolescent and Young Adult Health Outcomes and Patient Experience (AYA HOPE) study, a population-based cohort (n = 484), age 15–39, diagnosed with cancer 6–14 months prior, in 2007–2009. Unmet service needs were psychosocial, physical, spiritual, and financial services where respondents endorsed that they needed, but did not receive, a listed service. Linear regression models tested associations between any or specific unmet service needs and HRQOL, adjusting for demographic, medical, and health insurance variables. Results: Over one-third of respondents reported at least one unmet service need. The most common were financial (16%), mental health (15%), and support group (14%) services. Adjusted models showed that having any unmet service need was associated with worse overall HRQOL, fatigue, physical, emotional, social, and school/work functioning, and mental health (p’s < 0.0001). Specific unmet services were related to particular outcomes [e.g., needing pain management was associated with worse overall HRQOL, physical and social functioning (p’s < 0.001)]. Needing mental health services had the strongest associations with worse HRQOL outcomes; needing physical/occupational therapy was most consistently associated with poorer functioning across domains. Discussion: Unmet service needs in AYAs recently diagnosed with cancer are associated with worse HRQOL. Research should examine developmentally appropriate, relevant practices to improve access to services demonstrated to adversely impact HRQOL, particularly physical therapy and mental health services.

Access to Care

Rapid diagnosis, timely initiation of optimal treatment and good supportive care should be the gold standard for all patients who develop cancer, irrespective of age and where they live. This article reviews the evidence that teenagers/adolescents and young adults may be disadvantaged with regard to access to care. Delays in diagnosis and the reasons for them (patient and professional), low enrolment into clinical trials, suboptimal treatment strategies and place of care are addressed. We must access the voice of the young, address their needs, and involve them more in decisions concerning their own health. Progress is being made slowly in several countries and international collaboration linking patients, health care professionals, governmental and non‐governmental agencies is essential. Such international collaboration and focus, with specific research goals are suggested in order to make variation in access to optimal care become a thing of the past. Pediatr Blood Cancer 2008:50:1094–1098.

Trailblazers in Adolescent and Young Adult Oncology

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.

Discriminate gene lists derived from cDNA microarray profiles of limited samples permit distinguishing mesenchymal neoplasia ex vivo

Background Mesenchymal neoplasia comprises a heterogeneous group of tumors with over 200 benign neoplasms and 100 sarcomas. Currently, tumors are classified using histologic and immunocytologic characteristics, with diagnostic error rates reported as high as 40% of cases. As a feasibility study, our goal was to generate a preliminary discriminatory gene list for selected mesenchymal tumors, including sarcomas. This technique may enable an eventual molecular classification schema based on expression profiles that can complement current clinical and pathologic diagnostic procedures in mesenchymal tumors.Methods cDNA microarray analyses were preformed on connective tissue tumors obtained at time of surgical resection or biopsy. Messenger RNA (mRNA) from four general tumor classes was competitively hybridized against a human dermal fibroblast cell line comparator and the resulting gene expression profiles processed by ANOVA and linear discriminate analysis.Results The tissue classification involved 18 patients with malignant peripheral nerve sheath tumors, giant cell containing tumors, benign spindle cell lesions, or Ewing’s family of tumors. Lymph nodes from two patients served comparative purposes. Twenty-five differentially regulated genes considered most variable among the five tissue classes were identified. The tissues were segregated into five classes by linear discriminate analysis.Conclusions Linear discriminate analysis of cDNA gene expression profiles partitioned mesenchymal tumor classes, even when constrained by limited sample sizes.

Access and Models of Care

In the last ten years, the scientific community has started to pay increasing attention to the adolescent and young (AYA) adult age group. All over the world, dedicated programs have been founded and implemented at single institutions or as national programs, variously involving healthcare providers, national societies, governments and charitable institutions. A major issue to address regards the model of care to be used, as the traditional pediatric and adult health care systems have shown to be inadequate to deal with these patients’ peculiarities. This chapter discusses the possible models of care and whether a single new model should exist for AYA as well as it could feasibly be implemented; the key themes for an ideal AYA model; the various models of AYA cancer care which have been implemented internationally, with similarities or differences reflecting variations in local medical culture and resources. In addition, this chapter aims to address the way in which various barriers and enablers interact with each component of the definition of access to care, i.e. timeliness, utilization, and structure of health services, to influence outcomes for this patient group.

Primary Care Physicians' Decision Making Regarding Initial Oncology Referral for Adolescents and Young Adults With Cancer

PURPOSE The objectives of this study were to determine whether pediatricians are more likely than other primary care physicians (PCPs) to refer newly diagnosed adolescent and young adult patients with cancer to pediatric oncological specialists, and to assess the physician and patient characteristics that affect patterns of referral. METHODS A cross-sectional vignette survey was mailed to PCPs to examine hypothetical referral decisions as a function of physician characteristics and patient characteristics, including diagnosis, age, gender, race/ethnicity, family support, transportation, insurance, and patient preference for site of care. Pediatrician PCPs and nonpediatrician PCPs (family medicine, internal medicine, and emergency medicine physicians) practicing in North Carolina and in Washington State participated in the study. RESULTS A total of 406 surveys were completed (35.8% response rate). Sixty percent of pediatric PCPs referred their hypothetical patients with cancer to pediatric specialists (PSs), compared with only 37% of nonpediatric PCPs. Patient age also influenced referral patterns; 89% of 13-year-olds, 74% of 16-year-olds, 25% of 19-year-olds, and only 9% of 22-year-old patients were referred to a PS. Multivariate logistic regression demonstrated that diagnosis and physician practice setting also were associated with referral patterns. CONCLUSIONS Both patient age and PCP specialty were significant predictors of referral patterns in hypothetical vignettes of newly diagnosed adolescent and young adult patients with cancer. Pediatricians were more likely than nonpediatrician PCPs to refer patients to a PS. Referrals to PSs decreased dramatically between ages 16 and 19. Because the site of oncological care can impact outcomes, these data have the potential to inform awareness and education initiatives directed at PCPs.