Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

For children and young adults with T-cell immunophenotype acute lymphoblastic leukemia (ALL) does the administration of prophylactic cranial irradiation improve event-free and over-all survival.

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

My question compares survival outcomes among those who do receive prophylactic cranial irradiation versus those who do not receive prophylactic cranial irradiation.

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

Males and females aged 0-30 with T cell immunophenotype acute lymphoblastic leukemia. The question applies patients with any and all coexisting diagnoses.

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

The subgroup is the “T immunophenotype” patients with acute lymphoblastic leukemia.

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

Improvement in event-free and overall survival for these patients.

Describe any health-related risks, side effects, or harms that you are concerned about.

I am concerned that patients who receive prophylactic cranial irradiation will have an increased risk of secondary malignancies, endocrine disorders, and learning disabilities.

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

• Cancer

AHRQ Priority Populations

• Children
• Individuals with special health care needs, including individuals with disabilities or who need chronic care or end-of-life health care

Federal Health Care Program

• Medicaid
• Medicare
• State Children's Health Insurance Program (SCHIP)

Importance

Describe why this topic is important.

This topic is important because there are wide disparities in the use of prophylactic cranial irradiation among national and international pediatric oncology cooperative groups. Withholding prophylactic cranial irradiation may lead to increase relapse rates and deaths among pediatric patients with T cell acute lymphoblastic leukemia. However, the widespread use of prophylactic cranial irradiation may increase secondary malignancies, endocrine disorders, and learning disabilities in these patients without a meaningful gain in event free or overall survival. There is definite clinical equipoise around this question.

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

I am a practicing pediatric oncologist. My clinical work has exposed me to the different approaches by different cooperative groups. I am astounded that we have not sorted out whether T cell patients do or do not benefit from prophylactic irradiation. There is unlikely to be a randomized controlled trial to answer this question.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

There are at least 5 national and international pediatric oncology cooperative groups. Examining their different approaches to prophylactic cranial irradiation (pCRT) demonstrates the variations in clinical care and the controversy regarding what constitutes appropriate care for these patients.

1. The St. Jude’s Children’s Research consortium does not administer pCRT to any T cell patients
2. The Dana Farber ALL consortium administers pCRT to all T cell patients
3. The Berlin-Frankfurt-Munich Group (German cooperative group) administers pCRT to all T cell patients
4. The Dutch cooperative group does not administer pCRT to any T cell patients
5. The largest pediatric cooperative group, the international Children’s Oncology Group (based in the U.S.) administers pCRT to subsets of T cell patients based on the patients’ ages and clinical features

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

The answer will help inform decisions for treatment of T cell patients worldwide.

Describe the timeframe in which an answer to your question is needed.

There is no specific timeframe. We would like an answer as soon as possible.

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

The answer to this question will impact the care, survival rates, and future morbidities from cancer treatment in children with leukemia (a vulnerable population).

Nominator Information

Other Information About You: (optional)

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

The answer will help inform decisions for treatment of T cell patients worldwide.

Are you making a suggestion as an individual or on behalf of an organization?

Please tell us how you heard about the Effective Health Care Program

Tom Trikalinos, MD, PhD, Associate Director of the Tufts Medical Center, Evidence Based Practice Center suggested that I suggest this topic to the Effective Health Care program.