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Improved clinical trial enrollment in adolescent and young adult (AYA) oncology patients after the establishment of an AYA oncology program uniting pediatric and medical oncology divisions†
Article first published online: 27 DEC 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 14, pages 3614–3617, 15 July 2012
How to Cite
Shaw, P. H., Boyiadzis, M., Tawbi, H., Welsh, A., Kemerer, A., Davidson, N. E. and Kim Ritchey, A. (2012), Improved clinical trial enrollment in adolescent and young adult (AYA) oncology patients after the establishment of an AYA oncology program uniting pediatric and medical oncology divisions. Cancer, 118: 3614–3617. doi: 10.1002/cncr.26634
Presented in abstract and poster form at the Annual Meeting of the American Society of Clinical Oncology; June 4-10, 2010; Chicago, IL.
- Issue published online: 2 JUL 2012
- Article first published online: 27 DEC 2011
- Manuscript Accepted: 12 SEP 2011
- Manuscript Revised: 9 SEP 2011
- Manuscript Received: 7 JUL 2011
- young adult;
- clinical trial;
Since 1975, there has been a dramatic increase in the survival rates of pediatric and older cancer patients, but adolescent and young adult (AYA) patients ages 15 to 40 years have not had a similar improvement. Data indicate a direct correlation between increased cure rates and clinical trial enrollment.
The authors previously published data indicating inferior clinical trial enrollment when AYA patients were treated at an adult oncology center versus a pediatric oncology center. To address this deficit, a joint pediatric and adult AYA Oncology Program was established in July 2006 with the primary objective of improving outcomes by increasing therapeutic clinical trial enrollment in this population. Patients who were referred to that program from July 2006 through June 2010 were examined retrospectively to establish whether clinical trial enrollment increased compared with historic controls.
Fifty-seven patients were referred to the program from 2006 to 2010 (range, 12-16 new patients per year). Eight patients were referred for consultation only and were not treated at the University of Pittsburgh Cancer Institute or Children's Hospital of Pittsburgh. Five of 22 patients (23%) who received treatment at the pediatric cancer center were enrolled onto a clinical trial, whereas 9 of 27 patients (33%) patients who received treatment at the adult cancer center were enrolled. There was superior trial participation compared with the previous 3 years for those shared AYA patients who were treated at the adult center (P < .001).
Data from this study demonstrated that establishing a unified AYA oncology program can lead to improved clinical trial enrollment for patients who are treated at medical oncology centers. Cancer 2012;3614–3617. © 2011 American Cancer Society.
The past 30 years has witnessed a dramatic increase in the survival rates of pediatric and older cancer patients, but adolescent and young adult (AYA) patients ages 15 to 40 years have not experienced the same improvement. The reasons are multifactorial, but data indicate a direct correlation between improving cure rates and clinical trial enrollment.1 Despite this evidence, there is a considerable enrollment gap in the AYA population both in the United States2 and in the United Kingdom.3, 4
Our group previously published data indicating inferior clinical trial enrollment of AYA oncology patients compared with oncology patients aged <15 years at our children's hospital.5 We also noted an even larger disparity in clinical trial enrollment when these patients (ages 15-22 years) were received treatment at an adult oncology center (4% enrolled on trials) versus a children's hospital (26% enrolled on trials).1 To address this deficit, the pediatric oncologists at the Children's Hospital of Pittsburgh (CHP) and medical oncologist colleagues working through the University of Pittsburgh Cancer Institute (UPCI) established a joint AYA Oncology Program in July 2006. Through collaboration, the primary objective of this program was and is to improve outcomes by increasing clinical trial accrual in this population. The main objective of the current study was to determine whether there has been improved clinical trial enrollment in AYA patients who attended both cancer centers since the inception of the program.
MATERIALS AND METHODS
We reviewed patients who were referred to our AYA program from July 2006 through June 2010 to determine whether clinical trial enrollment was increasing versus historic controls from 2003 to 2006 at the same institutions. We examined enrollment in therapeutic clinical trials only. Newly diagnosed oncology patients ages 15 to 22 years who attended CHP or the UPCI through the AYA Oncology Program from 2006 to 2010 were eligible for the analysis. The data on patients ages 15 to 22 years who were not directly referred or discussed through the AYA program and were treated at either center were not included in our analysis. Patients outside of the AYA age range could be evaluated by our program if they had a diagnosis that was more frequent in the pediatric and young adult population versus the adult population (e.g., osteosarcoma), but they were not included in our analysis of clinical trial enrollment.
Diagnoses and clinical trial enrollment status for patients who received treatment at the UPCI between 2003 and 2006 were extracted from a billing records database. Cancer diagnoses and clinical trial enrollment status for patients who received treatment at CHP during this period were extracted from a pre-existing cancer registry and from an AYA oncology registry that was started with our program. All patients at CHP who were enrolled on a clinical trial were enrolled on a disease-specific phase 3 Children's Oncology Group (COG) trial. Some patients enrolled at the UPCI were treated on either COG trials or on single-institution medical oncology phase 1 trials. The enrollment of patients on COG trials at the UPCI is made possible through a shared Institutional Review Board (IRB) and a collaboration between oncologists, nurses, and cancer registrars at both centers. We compared the clinical trial enrollment between groups using chi-square tests. The investigators obtained approval from the University of Pittsburgh IRB to perform the database reviews for this study.
From July 2006 through June 2010 (fiscal years [FY] 2006-2009), 57 patients ages 15 to 22 years were referred to our program from 9 different area hospitals. In the first year of the program, FY 2006, there were 16 referrals, followed by 13 referrals in FY 2007, 12 referrals in FY 2008, and 16 referrals in FY 2009. The median age of all patients evaluated was 22 years (range, 13-75 years). Only 6 of the 57 patients were aged >40 years at the time of referral (the mean age of all patients was 24.3 years). Their diagnoses included both solid and hematologic malignancies, as indicated in Figure 1. After diagnosis and initial consultation, not all patients who were referred to our program were treated at 1 of our hospitals, and 8 patients returned to their referring oncologist for treatment. This explains why the total number of patients analyzed for the clinical trial enrollment rate is <57. Sites of treatment by diagnosis are illustrated in Figure 2.
For the patients who received treatment at CHP and the UPCI, we examined and compared clinical trial enrollment rates. Nine of 27 referred patients who received treatment at the UPCI were enrolled on a clinical trial (33%), whereas 5 of 22 referred patients who received treatment at CHP (23%) were enrolled. Two patients with osteosarcoma were enrolled on a trial at each center (a phase 3 trial at CHP and a phase 1 trial at the UPCI) and, thus, were counted separately for each institution. In addition, 3 patients were not enrolled on trials that were open. One patient who received treatment at CHP for acute lymphoblastic leukemia was not placed on an open clinical trial because of parental preference. Two patients with acute myeloid leukemia who received treatment at the UPCI were not enrolled in the open trial—1 because she was not interested and the other because she was rendered ineligible because she was pretreated with hydroxyurea.
The diagnoses of the 14 patients who were enrolled on trials through the AYA Oncology Program are indicated in Figure 1. In the 3 years before the start of the AYA program, 4% of the patients in this age range who received treatment at the UPCI were enrolled on therapeutic clinical trials, whereas those who received treatment at CHP were enrolled at a rate of 26%.1 There was no difference in the enrollment rate for patients who received treatment at CHP compared with historic data or with patients who were considered joint referrals during the study period. After the program was established, there was superior therapeutic clinical trial participation when we compared referred patients versus all new AYA patients who received treatment at the UPCI during the previous 3 years (P < .001).
Survival rates of cancer patients ages 15 to 40 years have remained virtually unchanged over the last 30 year, whereas older patients and younger patients have experienced significant progress in outcome improvement.6 The reason that cure rates in this underserved population have not improved as much as younger patients probably is multifactorial, but there is evidence that a lack of clinical trial enrollment may play a role.6, 7
The availability of clinical trials, in turn, depends on where the patient is treated, and data indicate that most AYA patients are not treated in academic centers, where most cooperative oncology group trials are available. A study of the pattern of treatment of AYA oncology patients in Ohio revealed that patients in this age group often are treated in a variety of different settings, including pediatric, adult academic, and community hospitals. In that study, 76% of oncology patients aged 15 years received treatment at pediatric oncology centers in the state, and that rate which dropped to 36% among patients aged 17 years and to 23% among patients aged 18 years.8 Therefore, most of the patients who fall within the AYA age group were not seen at the centers that offered the most clinical trials for their specific diseases.
Our previously published findings indicated that, within our own pediatric oncology center, patients ages 15 to 22 years had significantly lower clinical trial enrollment (27%) versus younger pediatric patients (38%), and the percentage of patients in this age group who were treated on trials in our affiliated medical oncology center over the same period was even lower (4%).1, 5 To address this discrepancy, we established a cooperative AYA Oncology Program in 2006, in which oncologists at both centers could share expertise and clinical trials through the shared University of Pittsburgh IRB to improve clinical trial availability for the population up to age 40 years. The program was founded by pediatric oncologists who engaged medical oncology colleagues at the adult cancer center to create a formalized collaboration between the pediatric and medical oncology programs at the University of Pittsburgh Medical Center. Patients qualify for inclusion in the AYA program by falling within the group ages 15 to 40 years. Our AYA program meetings occur quarterly in the office of the director of the cancer center and are attended by pediatric oncologists, our designated AYA nurse practitioner at CHP, cancer registrars from both centers, clinical research nurses, as well as several medical oncology attending physicians. These meetings function less as tumor boards and more as programmatic updates, focusing on trials available at both centers, total number of accruals to date, and discussions on new ways to collaborate. We have discussed starting an AYA-specific tumor board, but this has not yet been established. This effort improved communication between the teams to discuss patients both informally and at tumor boards. The shared IRB at the University of Pittsburgh allowed for the addition of medical oncologists as coinvestigators to COG studies, which has facilitated screening and has led to increased opportunities for clinical trial enrollment for our patients as a whole. By making more protocols available to these patients, our ongoing goal is to increase enrollment and, consequently, improve overall survival rates. There is not one model on how to establish an AYA program, because each medical center has its own structure and relationship between pediatric and medical oncology divisions. As long as there is ongoing communication between champions of AYA oncology care on both ends of the age spectrum, better care can be provided to these patients whether they are treated by pediatric, medical, or AYA-specific oncology teams.
Our data from 2006 to 2009 since the founding of our program demonstrate that, for AYA patients who were referred to the program and treated at the adult center, there was a significant increase in clinical trial enrollment compared with historic controls from 4% to 32%. One weakness in our data and analysis is that the overall low total number of patients impairs the statistical power. Therefore, it is impossible to draw broad conclusions even with a P value < .05. Still, we were encouraged by the trend toward improved clinical trial participation. Another weakness of our research is that we compared different databases: one from our AYA Oncology Program and another database based on billing and coding. In addition, for the period from 2006 to 2009 at the UPCI, we do not know the total number of all AYA patients who were treated or their clinical trial enrollment status. This is because patient data were maintained on several databases, which are in the process of being consolidated. To our knowledge, no other study to date has studied the impact of establishing an AYA oncology program on clinical trial enrollment.
Comparing the enrollment rates of the AYA patients who received treatment at CHP versus historic controls at first appears to indicate a decrease in the percentage of AYA patients who were enrolled on trials (23% from 27%), but it is important to keep in mind that the 22 patients who received treatment at CHP through collaboration in the AYA program did not include the new oncology patients ages 15 to 22 years who were seen by the pediatric oncology team at our center over the 4 years we studied. Most new AYA patients at CHP are not discussed with our medical oncology colleagues if they have a common pediatric diagnosis, regardless of whether there is a clinical trial available. These patients were offered all appropriate IRB-approved trials and were enrolled at rates similar to those in the previous 3 years.
Our data demonstrate that establishing a unified AYA oncology program led to improved clinical trial enrollment in patients ages 15 to 22 years who received treatment at a medical oncology center in collaboration with pediatric oncologists. We believe that this approach also may improve enrollment at other tertiary care medical centers that serve these patients. It is too soon to conclude whether enrolling more of these patients on clinical trials will translate into improved disease-free survival, but we hope our collaborative program will serve as a blueprint for other oncology centers to enhance the care provided to AYAs with cancer.
No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES
The authors made no disclosures.
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- 7Young adults with leukemia in the United States: lack of clinical trial participation and mortality reduction during the last decade [abstract]. Proc Am Soc Clin Oncol. 2004; 23: 586., , .