© 2006 European Society for Medical Oncology
editorial |
Is there a place for routine imaging for patients in complete remission from aggressive lymphoma?
University of Nebraska Medical Center, Omaha, NE, USA
* (E-mail: eryan{at}unmc.edu)
Routine imaging of patients with aggressive lymphoma in complete remission is standard practice in most of the United States. The timing (i.e. every 6 months or every year), the duration (i.e. usually for 3–5 years) and the type of image performed (i.e. CT scan, PET scan or both) vary among clinicians. However, these studies are often routinely performed by academic oncologists and private practitioners. In this issue of the Annals, Liedtke et al. describe 108 patients with relapsed aggressive non-Hodgkin's lymphoma who were treated with ifosfamide, carboplatin and etoposide (ICE) followed by an autologous hematopoietic stem cell transplant in responding patients [1
]. Eighty per cent of the patients in the study had their relapse diagnosed as part of an evaluation for new symptoms or physical findings, and 20% of the patients had their diagnosis of relapse made because of findings from routine imaging. They found that patients whose relapse was discovered as a result of routine imaging were more likely to have low risk disease and had a slight, but not significant, increase in 5-year survival (i.e. 54% versus 43%). However, the proportion of detecting relapse based on routine versus non-routine imaging would have been better quantified if the study had included patients who did not develop relapse.
Routine imaging for all patients who achieve a complete remission from aggressive lymphoma is an expensive undertaking. At the University of Nebraska Medical Center biannual CT scans of the chest, abdomen and pelvis for 5 years add approximately $50 000 to a patient's charges and biannual CT scans and PET scans add approximately $100 000 to the cost of their care. It is important that an advantage comes from this investment. One advantage might be the patient's comfort from knowing the scans are normal. However, this would have to be balanced against the anxiety associated with each test, and the disadvantage of teaching patients that they are still ‘patients’ and not well. Some of them end up living from scan to scan.
Given the above issues, it can be argued that routine images in complete remission for a patient with a curable malignancy such as an aggressive lymphoma should provide a survival advantage if they are to be done. Any improved survival would presumably come from early diagnosis of relapse and a better chance for cure with second-line therapy. Support for a better outcome with routine images in complete remission for patients with aggressive lymphoma is not extensive. In studies of patients with aggressive non-Hodgkin's lymphoma and in patients with Hodgkin's disease, a high proportion of relapses are detected at unscheduled visits sought by the patient because of new symptoms [2–5]. Most studies of routine imaging in remission have utilized CT scans but a brief report of the use of PET scans to detect early relapse in patients with Hodgkin's disease does not suggest that it would be more useful [6]. A major difficulty is the infrequency of relapse at any particular point in time and the imperfect specificity and sensitivity of the available tests. Radford et al. [5] found one relapse per 68 visits in patients with Hodgkin's disease. Our experience with patients with aggressive non-Hodgkin's lymphoma is approximately one relapse diagnosed for each 40–45 visits in the first 5 years of follow-up. While PET scans have not been as closely studied, sensitivity and specificity of CT scans in lymphoma have been well studied. Sensitivity (i.e. the chance that the scan will be abnormal in a patient with active disease) has varied from 26% to 100% with an average of 62%. The specificity (i.e. the chance that an abnormal test will reflect active lymphoma) has varied from 35% to 100% with an average of 92%.
Routine imaging is, in fact, screening for early relapse. The value of screening tests has been studied extensively. Any advantage for screening depends on the sensitivity and specificity of the test and the frequency of the event being screened for in the population being screened. Whether screening for early relapse can hope to increase survival will be dependent on the accuracy at finding relapse and the efficacy of second-line therapy. Most relapses for patients with aggressive lymphoma are found because of symptoms, new physical findings or abnormal laboratory tests such as LDH or sedimentation rate. In the majority of patients in most series, discovery of relapse is diagnosed at an unscheduled visit. The probability that a given abnormal screening test done in patients with malignancy in an attempt to discover relapse will represent actual disease can be calculated from the following formula:
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Available data certainly does not show convincingly that routine imaging in complete remission for patients with aggressive lymphoma provides a therapeutic advantage. We would not accept an expensive treatment based on this level of evidence. Given the expense—both financial and emotional—associated with routine images in remission, it is time that a randomized trial be done to test its efficacy as suggested by Liedtke et al. [1]. Until then, routine imaging for patients in complete remission who are asymptomatic, without abnormal physical findings and who have normal laboratory studies is probably not appropriate based on the available data.
References
1. Liedtke M, Hamlin PA, Moskowitz CH, Zelenetz AD. Surveillance imaging during remission identifies a group of patients with more favorable aggressive NHL at time of relapse: a retrospective analysis of a uniformly treated patient population. Ann Oncol 2006; 17: 909–913.
2. Weeks JC, Yeap BY, Canellos GP, Shipp MA. Value of follow-up procedures in patients with large-cell lymphoma who achieve a complete remission. J Clin Oncol 1991; 9: 1196–1203.[Abstract]
3. Elis A, Blickstein D, Klein O et al. Detection of relapse in non-Hodgkin's lymphoma: role of routine follow-up studies. Am J Hematol 2002; 69: 41–44.[Medline]
4. Guppy AE, Tebbutt NC, Normal A, Cunningham D. The role of surveillance CT scans in patients with diffuse large B-cell non-Hodgkin's Lymphoma. Leuk Lymphoma 2003; 44: 123–125.[CrossRef][ISI][Medline]
5. Radford JA, Eardley A, Woodman C et al. Follow up policy after treatment for Hodgkin's disease: too many clinical visits and routine tests? A review of hospital records. BMJ 1997; 314–343.
6. Jerusalem G, Beguin Y, Fassotte MF et al. Early detection of relapse by whole-body positron emission tomography in the follow-up of patients with Hodgkin's disease. Ann Oncol 2003; 14: 123–130.
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