The value of routine CT surveillance monitoring of pediatric patients for recurrence of Hodgkin lymphoma has been unclear. A study of CT surveillance recently reported by Stephan D. Voss, MD, PhD, and colleagues from the Children’s Oncology Group (COG) in the Journal of Clinical Oncology showed that most relapses occurred early or were signaled by clinical changes and that detection of infrequent late relapses by surveillance imaging did not appear to affect survival.

In this study, Dr. Voss and colleagues analyzed data from 216 patients aged ≤ 21 years who were enrolled in the COG Pediatric Oncology Group 9425 trial between 1997 and 2001.¹ All patients had biopsy-proven classical Hodgkin lymphoma and intermediate-risk (25%) or high-risk (75%) disease, and all had responded to ABVE-PC therapy (doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide) followed by radiation therapy. Patients were followed with surveillance CT scans at 0, 6, 12, 24, and 30 months.

Most Relapses Signaled by Clinical Changes

During a median follow-up of 7.4 years, 25 patients (12%) experienced relapse. Relapse was local in 23 patients. The median time to relapse was 7.6 months (range, 0.2-48.9 months). In 19 (76%) of the 25 patients with relapse, relapse was suspected on the basis of reported changes in physical symptoms, lab values, or physical examination findings. Symptoms and clinical findings in patients with relapse included palpable lymphadenopathy in eight patients, recurrent ‘B’ symptoms in two, and combinations of pain, weight loss, adenopathy, and abnormal lab findings in eight.

Relapse Rates

Six patients (24%) with no symptoms at the time of relapse had relapse detected by routine imaging. In these patients, relapses were detected by CT alone (n = 3), gallium scintigraphy alone (n = 1), CT and gallium scintigraphy (n = 1), or gallium scintigraphy, magnetic resonance imaging, and positron emission tomography (PET; n = 1). An additional patient had relapse detected by CT performed as part of a workup for potential pneumonia. Two of the six patients had relapse detected within the first year after completing therapy, and four (16% of patients with relapse) had relapse detected by surveillance imaging later than 1 year after treatment—ie, after the period during which risk of relapse is highest. The late asymptomatic relapses occurred both in patients with intermediate-stage disease (n = 1) and in those with advanced-stage disease (n = 3).

The majority of relapses occurred at previously involved sites or at both previously involved and new sites, with relapse at only new sites occurring in two patients (8%). Relapses occurred with similar frequency in patients with intermediate-stage and advanced-stage disease (11% and 12%) and among patients with slow early response (9 of 77, 12%) and rapid early response (16 of 132, 12%). The investigators defined rapid early response as “≥ 50% reduction in the sum of the products of the perpendicular diameters of measurable lesions and negative gallium scan after three chemotherapy cycles.” Failure to achieve rapid early response was considered slow early response.

Relapses occurred across all Hodgkin lymphoma histologies and did not occur more frequently in patients with bulk disease. The median time to relapse was significantly longer in patients with rapid early response vs those with slow early response (11.5 vs 2.2 months, P = .044).

Most Relapses Occurred in First Year

Overall, 16 (64%) of the 25 relapses occurred within the first year after the end of treatment. Most patients with relapse were successfully treated with salvage therapy, with 5-year event-free survival of 84% and 5-year overall survival of 95% reported in the entire patient population. Six patients died from relapsed disease, with all of these patients having relapse within 1 year of completing treatment. There were no deaths in patients with relapse detected after 1 year, irrespective of how relapse was detected.

Although the numbers of patients involved in the analysis of overall survival in patients with relapse was small, overall survival was significantly greater in patients with relapse after 1 year compared with patients having relapse within 1 year (P = .04). Due to small sample sizes, there were no significant differences between overall survival in patients with relapse during the first year (detected either by imaging or by clinical change) and overall survival in patients with relapse after 1 year detected by clinical change or overall survival in patients with relapse after 1 year detected by imaging.

The study thus showed that approximately 1,080 CT scans (five planned scans per patient) were performed off therapy to detect four late asymptomatic relapses and indicated that the use of surveillance imaging to detect these relapses did not have an impact on overall survival. There is concern that CT scanning in children, even with optimized dosing, may increase risk of cancers later in life. Some data on diagnostic imaging in pediatric patients with cancer indicate that those with neuroblastoma and lymphoma have the highest cumulative radiation doses, primarily from CT scans and nuclear medicine examinations. The authors noted that due to the high curability of Hodgkin lymphoma with current treatment, there has been a renewed emphasis on limiting long-term treatment-related morbidity, including morbidity associated with diagnostic imaging.

Surveillance CT scans are also expensive. The authors estimated that in the recently completed COG intermediate-risk Hodgkin lymphoma study AHOD0031, some 10,000 surveillance CT scans were scheduled, per protocol, to be performed after 1 year post-treatment in the more than 1,700 patients enrolled, with an aggregate cost to the health-care system of at least $3.48 million. This study is now closed to accrual but patients are still being monitored off therapy; an amendment to the original protocol has been submitted to reduce the number of follow-up surveillance imaging examinations required.

Conclusions

As stated by the authors, “On the basis of these findings, it is our conclusion that CT is overutilized for the routine surveillance of [Hodgkin lymphoma], with little impact on overall outcome in patients who do not experience an early relapse…. This study … identifies an opportunity to reduce both unnecessary medical expense and radiation exposure by decreasing the number of imaging studies being routinely performed on patients with [Hodgkin lymphoma]…. [W]e recommend reducing the routine use of CT surveillance imaging to the initial 12 months after therapy.” ■

Disclosure: The authors of the COG study reported no potential conflicts of interest.

Reference

1. Voss SD, Constine LS, Chauvenet A, et al: Surveillance computed tomography imaging and detection of relapse in intermediate- and advanced-stage pediatric Hodgkin’s lymphoma: A report from the Children’s Oncology Group. J Clin Oncol. June 11, 2012 (early release online).