This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bowers, D. C. Articles by Oeffinger, K. C. Search for Related Content PubMed Articles by Bowers, D. C. Articles by Oeffinger, K. C. Related Articles Related Correspondence Social Bookmarking                            What's this?

In Reply:

Department of Pediatrics, University of Texas Southwestern Medical School, Dallas, TX

Kevin C. Oeffinger

Departments of Pediatrics and Internal Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

We appreciate the thoughtful comments by Dorresteijn et al about our article.¹ We agree that mantle radiation in the "atherosclerotic-naive patient" may induce atherosclerotic-like lesions in the carotid artery, similar to changes seen in the coronary arteries.² However, as pointed out by Dorresteijn et al, data on the site and source of the stroke were not available in our study. Thus, some of these strokes could have been cardioembolic or hemorrhagic in nature.

We do not agree with the suggestion of standard screening of the carotid arteries with duplex ultrasound for all Hodgkin's disease survivors who have been treated with mantle radiation. In our study, we reported that the incidence of stroke in the sibling comparison group was 8.0 per 100,000 person-years, and the incidence among Hodgkin's survivors treated with mantle radiation was 109.8 per 100,000 person-years. The adjusted relative risk for stroke in Hodgkin's survivors treated with mantle radiation was 5.62 (95% CI, 2.59 to 12.25; P < .0001). Though this represents a significant increase in relative risk, it remains a rare event in both populations. Based on these figures, the minimum number of Hodgkin's survivors treated with mantle radiation who would need to be screened to prevent a stroke is 982. The number needed to screen is the reciprocal of the absolute difference in incidence between populations.³ This number, however, assumes that 100% of excess potential strokes among Hodgkin's survivors treated with mantle radiation could be accurately identified by duplex screening, or some other form of screening, and then prevented; assumptions that are clinically unrealistic. Thus, the number needed to screen is likely well over a thousand Hodgkin's survivors. Data are not available to determine the false-positive or negative rates or the predictive value of carotid artery duplex ultrasound in this population. Given the rarity of the outcome, if the false-positive rate is appreciable, we may in fact cause more harm than benefit through screening by increasing costs and subsequent morbidity that is associated with further testing and by increasing survivor anxiety. Similarly, if false-negative rates are high, many more subjects may need to be screened in order to identify and subsequently prevent a single stroke.

Therefore, as suggested in our article, further detailed study is warranted to understand this risk and the methods to reduce the risk. Because the outcome is rare, a nested case-control study within a large cohort, such as the Childhood Cancer Survivor Study, is needed to evaluate an ample number of cases to determine the site and source of strokes and potential modifying risk factors. Knowledge regarding additional factors that increase risk, including comorbidities and genetic determinants, could lead to better defining a population where the risk is sufficiently high that the cost-benefit for an appropriate form of screening would be justified. Second, a well-designed and adequately powered multicenter study of asymptomatic young adult Hodgkin's survivors and a population-based comparison group is needed to determine the prevalence of clinically significant carotid artery disease and to assess the measurement metrics (false-positive/negative rates, positive/negative predictive value rates) of carotid artery duplex ultrasound. Without this information, we cannot recommend universal screening in this population at the present time.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Bowers DC, McNeil DE, Liu Y, et al: Stroke as a late treatment effect of Hodgkin's disease: A report from the Childhood Cancer Survivor Study. J Clin Oncol 23:6508-6515, 2005[Abstract/Free Full Text]

2. Brosius FC 3rd, Waller BF, Roberts WC: Radiation heart disease: Analysis of 16 young (aged 15 to 33 years) necropsy patients who received over 3,500 rads to the heart. Am J Med 70:519-530, 1981[CrossRef][Medline]

3. Rembold CM: Number needed to screen: Development of a statistic for disease screening. BMJ 317:307-312, 1998[Abstract/Free Full Text]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Correspondence

• Stroke As a Late Treatment Effect of Hodgkin's Disease
  Lucille Désirée Dorresteijn, Fiona Anne Stewart, and Willem Boogerd
  JCO 2006 24: 1480 [Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bowers, D. C. Articles by Oeffinger, K. C. Search for Related Content PubMed Articles by Bowers, D. C. Articles by Oeffinger, K. C. Related Articles Related Correspondence Social Bookmarking                            What's this?