The Role of Imaging in Relapse Detection During Follow up: a Fifteen-Year Single Center Experience.

Non Hodgkin Lymphoma represent a category of hematological malignances which are chemo and radio-sensitive; improvements in their treatment had been achieved by immunotherapeutic approaches. However some patients will relapse after achieving complete remission (CR). Obviously, in order to detect and possibly treat them as soon as possible, a follow up strategy has to be planned. The more diffuse follow up have been planned years before the introduction of innovative methods and imaging techniques, suggesting the opportunity to revise these programs. In particulary it is not still clear which is best techniques useful to properly follow this patient. Recently new interesting methods are available like PET, CT-PET and minimal residual disease (MRD) monitoring.

418 NHL patients -both low and high grade- treated at our institution from 1995 to 2005 who achieved a CR status according to Cheson criteria have been evaluated. LH NHL included follicular lymphoma, lymphoplasmocytic lymphoma, Marginal zone lymphoma, and small lymphocytes lymphoma. In the HG NHL, we included T-cells lymphomas, diffuse large cell lymphoma, lymphoblastic lymphoma, Mantle cell lymphoma, anaplastic lymphoma, Burkitt lymphoma. Patient characteristics are summarized in Table 1. Follow up is planned for 5 years divided in two periods: in the first two years patients are evaluated every 3 months and in the following three years every sixth month. At each visit physical examinations, blood testing (blood count, chemistry) are performed; for imaging techniques we alternate a whole body CT scans to ultrasounds and chest X-ray coupled. Bone marrow samples for both pathological and molecular analysis are collected every six months in the first period and once a year afterwards. PETs were usually performed when CT showed uncertain findings.

There were 431 events, with 188 first relapses, 86 second, 18 third, 4 fourth and 1 fifth relapses. Relapse rate was similar among high and low grades, (37% and 35 % respectively) but time to relapse was longer for low grades (18.2 months vs 8.9 months). There was not relationship between IPI status and relapse rate. 72 % of relapse was at the same site of diagnosis. Relapses were detected by ultrasound in 139 cases (32 %), CT scans in 110 (25.5%) and by physical examination in 62 (14.4%). Remaining patients' relapse were diagnosed with other techniques (lab test, gastroscopy, NRM) New techniques as MRD monitoring, PET or PET/CT were not available for many patients, anyway MRD monitoring was able to detect disease re-appearance in 2%, and we had a total of 28 cases (6,5%) of relapse diagnosis with PET, but we noted a total of 18,5 % of false positive.

Many papers from literature raised many questions about which is the best techniques to follow patients. Many authors showed how symptoms onset and clinical findings appeared to be the more important for relapse detection compared to imaging before and during CT era. Some works pointed out also that even when CT detected earlier a relapse that do not translate in a survival advantage. Recently much interest has been focused on PET, CT-PET and MRD. They two appeared to be very important as prognostic tolls but their role for follow up purpose is still debatable. On the basis of clinical data and of these consideration routine PET is not recommended during follow up. Unfortunately PETs and MRD monitoring were not available for the majority of our patients, diagnosed in the nineteen's. In conclusion in our experience we observed some usefulness of CT scans and ultrasounds but we must recall that the majority of literature is not consistent with our results. Considering our experience and data from literature probably imaging should be performed routinely at the end of therapy, and during follow up only on the basis of presentation and clinical suspicion. As a matter of fact NCCN reviewed its guidelines do not suggesting a wide use of routine imaging. Further investigation by clinical and randomized trials are certainly needed to better understand, in particular the role of PET-PET/CT for follow up purpose.

No relevant conflicts of interest to declare.