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Should the use of surveillance imaging in diffuse large B-cell lymphoma be discontinued?

TO THE EDITOR: As a result of ongoing improvements in diagnosis and treatment, the survival rate for patients with lymphoma continues to increase; however, these patients remain at high risk of developing second malignancies. Thompson et al recently published an article describing the results on the utility of post-therapy surveillance imaging in a large, prospectively enrolled cohort of patients with diffuse large B-cell lymphoma (DLBCL) from the upper Midwest of the United States and confirmed their results in an independent cohort of patients from France. The authors concluded that their data do not support the use of routine surveillance imaging for follow-up of DLBCL. Even if these results provide an interestingly overview of this topic, unfortunately, the article fails to emphasize one key concept: the risk of second malignant neoplasm among patients with DLBCL and the potential utility of an early diagnosis of second cancer. Brennan et al studied the occurrence of second primary cancers in 109,000 patients with non-Hodgkin lymphoma (NHL) from 13 cancer registries and showed a 47% (95% CI, 43% to 51%) overall increase in the risk of primary cancer after NHL. Furthermore, five of the cancer sites (lung, bladder, stomach, Hodgkin lymphoma, and myeloid leukemia) showed patterns of risk consistent with treatment effect and a greater risk correlated with young age, when treatment is likely to be more intensive. In a British study of 2,456 patients with NHL, the relative risk (RR) and absolute excess risk (AER) of all malignancies (excluding nonmelanomatous skin cancers and NHL) were 1.3 (95% CI, 1.1 to 1.6) and 15.4 per 10,000 personyears, respectively. Dores et al, in a report that included almost 74,000 patients with NHL in the SEER program, found that the RR and AER of all subsequent cancers (excluding NHL) were 1.14 (P .01) and 19 per 10,000 person-years, respectively. Furthermore, a significantly elevated risk of subtypes of GI cancers, including cancers of small intestine, stomach, anus, pancreas, and colon, have been reported in NHL survivors. Mudie et al found that the risk of colorectal cancer was increased significantly only in chemotherapy-treated patients (RR, 2.1; 95% CI, 1.1 to 3.6), particularly in those treated with CHOP (RR, 2.4; 95% CI, 1.1 to 4.3), but no occurrences were observed in those treated with RT alone. The risk of lung cancer is significantly increased after either radiation therapy alone or chemotherapy alone. The chemotherapy regimens that have been associated with lung cancer risk include cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP). Mudie et al reported that the RR of lung cancer was significantly increased in a CHOP subcohort (RR, 2.1; 95% CI, 1.1 to 3.7), but not in patients given chlorambucil (RR, 1.1; 95% CI, 0.4 to 2.4). Lung cancer risk appears to be higher in male survivors of NHL, potentially as a result of a higher prevalence of smoking in men; however, the contribution of tobacco history to treatment-related lung cancer risk after NHL has not been directly assessed. In addition to lung cancer, population-based studies have shown a significantly increased risk of mesothelioma even when limited to irradiated patients with NHL. Interestingly, patients whose lung tumors were detected incidentally had a significantly longer survival time than those who were symptomatic. In our experience with a median follow-up time of 40 months, the median survival time for patients with incidentally detected lung cancer has not been reached, whereas the median survival time for patients with symptomatic disease at diagnosis was 9.1 months. Most cancers have a better prognosis if diagnosed earlier in their natural history, and even if this basic observation is not in itself sufficient to justify screening in an asymptomatic population, effective screening methods should be included in patients in follow-up for a second cancer. Furthermore, it would seem logical to be able to prospectively identify patients subgroups that might be at heightened susceptibility of developing treatment-associated second cancers to modify planned treatment approaches or select alternative treatment strategies.