Fadi Najjar

A residual mass after treatment of lymphoma is a clinical challenge, because it may represent vital tumor as well as tissue fibrosis. Metabolic imaging by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) offers the advantage of functional tissue characterization that is largely independent of morphologic criteria. We compared 18F-FDG PET to computed tomography (CT) in the posttreatment evaluation of 54 patients with Hodgkin's disease (HD) or intermediate/high-grade non-Hodgkin's lymphoma (NHL). Residual masses on CT were observed in 13 of 19 patients with HD and 11 of 35 patients with NHL. Five of 24 patients with residual masses on CT versus 1 of 30 patients without residual masses presented a positive 18F-FDG PET study. Relapse occurred in all 6 patients (100%) with a positive 18F-FDG PET, 5 of 19 patients (26%) with residual masses on CT but negative 18F-FDG PET, and 3 of 29 patients (10%) with negative CT scan and 18F-FDG PET studies (P </=.0001). We observed a higher relapse and death rate in patients with residual masses at CT compared with patients without residual masses at CT (progression-free survival at 1 year: 62 +/- 10 v 88 +/- 7%, P =. 0045; overall survival at 1 year: 77 +/- 5 v 95 +/- 5%, P =.0038). A positive 18F-FDG PET study was even more consistently associated with poorer survival: compared with patients with a negative 18F-FDG PET study, the 1-year progression-free survival was 0% versus 86% +/- 5% (P <.0001) and the 1-year overall survival was 50% +/- 20% versus 92% +/- 4% (P <.0001). The detection of vital tumor by 18F-FDG PET after the end of treatment has a higher predictive value for relapse than classical CT scan imaging (positive predictive value: 100% v 42%). This could help identify patients requiring intensification immediately after completion of chemotherapy. However, 18F-FDG PET mainly predicts for early progression but cannot exclude the presence of minimal residual disease, possibly leading to a later relapse.

BACKGROUND AND OBJECTIVES: Accurate staging is essential in order to determine appropriate treatment in Hodgkin's disease (HD). (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) offers the advantage of metabolic imaging that is largely independent of morphologic criteria. In the present study we evaluated the role of (18)F-FDG PET compared to routine procedures for the staging of patients with HD. DESIGN AND METHODS: Thirty-three patients with HD underwent standard staging procedures (clinical examination, laboratory screening, chest X-ray, computed tomography (CT) of the chest and abdomen and bilateral bone marrow biopsies) and a whole-body (18)F-FDG PET study. In clinical examination, an isolated lymph node > 1 cm or multiple lymph nodes > or = 1 cm in size were considered abnormal. Positive findings at both clinical examination or CT and (18)F-FDG PET were regarded as actual locations of disease. Negative findings with both methods were regarded as true negative (no involvement by HD). In cases of discrepancy, response to treatment and follow-up data were used to assess the overall accuracy of the patient's original evaluation. RESULTS: Completely concordant results in lymph node staging were observed in 20 patients. The two staging procedures indicated complementary information in 1 patient. Conventional staging indicated more pathologic lymph node areas in 6 patients (at least 1 false positive). (18)F-FDG PET showed more sites in 6 patients. The sensitivity of (18)F-FDG PET in detecting all known pathologic lymph nodes was 83% for peripheral lymph nodes, 91% for thoracic lymph nodes and 75% for abdominal and pelvic lymph nodes. Conventional staging procedures and (18)F-FDG PET indicated the same tumor stage in 26 patients. Based on (18)F-FDG PET, downstaging was suggested in 4 patients, including a biopsy-proven case. However in 1 of these cases this was incorrect. (18)F-FDG PET suggested upstaging in 3 patients. Based on conventional staging or (18)F-FDG PET the same treatment strategy was defined in 32 patients. In one patient (18)F-FDG PET downstaged disease extension (stage IIIA-->IIA) that would have suggested radiotherapy as a possible treatment option. INTERPRETATION AND CONCLUSIONS: (18)F-FDG PET provides an easy and efficient whole-body method for the evaluation of patients with HD. (18)F-FDG PET never missed tumor masses >1 cm. (18)F-FDG PET detected additional sites of disease not seen by conventional procedures and identified absence of disease in some sites suspected to be involved. However, in our patients this did not translate into changes in treatment strategy.

BACKGROUND AND OBJECTIVE: Early recognition of the ineffectiveness of chemotherapy could result in lower cumulative drug toxicity and tumor burden at the start of salvage therapy, which might improve clinical outcome. Therefore, we studied the value of (18)F-FDG PET for early evaluation of response in patients with non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: We studied 28 patients by (18)F-FDG PET after a median of 3 cycles of polychemotherapy. The presence or absence of abnormal (18)F-FDG uptake was correlated to clinical outcome (median follow-up: 17.5 months, range 4-47 months). RESULTS: Five of 28 patients still had increased (18)F-FDG uptake in one or more sites previously shown to be involved by lymphoma at baseline evaluation. Only one of these five patients entered complete remission (CR), whereas among the 23 patients with negative (18)F-FDG PET studies, two died of toxicity during chemotherapy and all the others entered clinical CR (p<0.00001). All five patients with and 7/21 patients without residual abnormal (18)F-FDG uptake relapsed or reprogressed (positive predictive value for relapse: 100%, negative predictive value: 67%). By Kaplan-Meier analysis, progression-free survival (PFS) at 1 and 2 years was respectively 20+/-18% and 0% for (18)F-FDG PET positive patients and 81+/-9% and 62+/-12% for (18)F-FDG PET negative patients (p=0.0001). Overall survival (OS) at 1 and 2 years was respectively 20+/-18% and 0% for (18)F-FDG PET positive and 87+/-7% and 68+/-11% for (18)F-FDG PET negative patients (p<0.0001). INTERPRETATION AND CONCLUSIONS: Persistent tumoral (18)F-FDG uptake after a few cycles of polychemotherapy is predictive of CR, PFS and OS in NHL. Further studies are warranted to determine whether (18)F-FDG PET has a predictive value independent from conventional prognostic factors. However, the sensitivity of qualitative (18)F-FDG PET imaging in identifying patients with a poor outcome was insufficient. Earlier evaluation after only one cycle of chemotherapy and quantitative analysis might increase the sensitivity of 18F-FDG PET is predicting treatment failure.

Whole-body metabolic information provided by 18F-FDG PET could help in the evaluation of lymphoma patients at diagnosis and follow-up. We studied 60 patients, 42 at initial presentation and 18 for disease recurrence (23 aggressive non-Hodgkin's lymphoma, 21 low-grade non-Hodgkin's lymphoma and 16 Hodgkin's disease). All patients underwent a clinical examination, computed tomography (CT) and a non-attenuated PET scan within 1 week. The patients received 222-296 MBq (6-8 mCi) 18F-FDG intravenously and emission scans were recorded 45-90 min later. 18F-FDG PET detected more lymph nodes than the clinical examination or CT, but this rarely resulted in upstaging (two patients). The concordance between PET and CT for the evaluation of the spleen, liver and digestive tract was quite good. Discordance was noted in 12 patients for the evaluation of bone marrow infiltration, but confirmation by MRI or focal biopsy was not always obtained. We conclude that non-attenuated 18F-FDG PET is an easy and efficient whole-body method for the evaluation of patients with lymphomas. Compared with conventional techniques, however, it does not appear to offer much improvement for staging but provides a satisfactory base for follow-up.