Karoline Spaepen

Use of Positron Emission Tomography for Response Assessment of Lymphoma: Consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma

PURPOSE To develop guidelines for performing and interpreting positron emission tomography (PET) imaging for treatment assessment in patients with lymphoma both in clinical practice and in clinical trials. METHODS An International Harmonization Project (IHP) was convened to discuss standardization of clinical trial parameters in lymphoma. An imaging subcommittee developed consensus recommendations based on published PET literature and the collective expertise of its members in the use of PET in lymphoma. Only recommendations subsequently endorsed by all IHP subcommittees were adopted. RECOMMENDATIONS PET after completion of therapy should be performed at least 3 weeks, and preferably at 6 to 8 weeks, after chemotherapy or chemoimmunotherapy, and 8 to 12 weeks after radiation or chemoradiotherapy. Visual assessment alone is adequate for interpreting PET findings as positive or negative when assessing response after completion of therapy. Mediastinal blood pool activity is recommended as the reference background activity to define PET positivity for a residual mass > or = 2 cm in greatest transverse diameter, regardless of its location. A smaller residual mass or a normal sized lymph node (ie, < or = 1 x 1 cm in diameter) should be considered positive if its activity is above that of the surrounding background. Specific criteria for defining PET positivity in the liver, spleen, lung, and bone marrow are also proposed. Use of attenuation-corrected PET is strongly encouraged. Use of PET for treatment monitoring during a course of therapy should only be done in a clinical trial or as part of a prospective registry.

Prognostic Value of Positron Emission Tomography (PET) With Fluorine-18 Fluorodeoxyglucose ([18F]FDG) After First-Line Chemotherapy in Non-Hodgkin’s Lymphoma: Is [18F]FDG-PET a Valid Alternative to Conventional Diagnostic Methods?

PURPOSE A complete remission (CR) after first-line therapy is associated with longer progression-free survival (PFS). However, defining CR is not always easy because of the presence of residual masses. Metabolic imaging with fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) offers the ability to differentiate between viable and fibrotic inactive tissue. In this study, we evaluated the value of PET in detecting residual disease and, hence, predicting relapse after first-line treatment in patients with non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS Ninety-three patients with histologically proven NHL, who underwent a whole-body [18F]FDG-PET study after completion of first-line chemotherapy and who had follow-up of at least 1 year, were included. Persistence or absence of residual disease on PET was related to PFS using Kaplan-Meier survival analysis. RESULTS Sixty-seven patients showed a normal PET scan after first-line chemotherapy; 56 of 67 remained in CR, with a median follow-up of 653 days. Nine of these patients with a residual mass considered as unconfirmed CR received additional radiotherapy. Only 11 of 67 patients relapsed (median PFS, 404 days). Persistent abnormal [18F]FDG uptake was seen in 26 patients, and all of them relapsed (median PFS, 73 days). Because standard restaging also suggested residual disease, 12 patients received immediate secondary treatment. In 14 of 26 patients, only PET predicted persistent disease. From these patients, relapse was proven either by biopsy (n = 8) or by progressive disease on computed tomography or magnetic resonance imaging (n = 6). CONCLUSION Persistent abnormal [18F]FDG uptake after first-line chemotherapy in NHL is highly predictive for residual or recurrent disease. In relapsing patients, PFS was significantly shorter after a positive scan than after a negative scan.

Can positron emission tomography with [18F]-fluorodeoxyglucose after first-line treatment distinguish Hodgkin's disease patients who need additional therapy from others in whom additional therapy would mean avoidable toxicity?

To assess the ability of restaging positron emission tomography (PET) scanning to predict clinical outcome after first‐line treatment in patients with Hodgkins disease, we included 60 patients with histologically proven HD, who underwent whole‐body [18F]‐fluorodeoxygenase ([18F]‐FDG)‐PET studies after first‐line treatment and with a follow‐up of at least 1 year. Persistence or absence of residual disease on PET was related to progression‐free survival (PFS) using Kaplan–Meier survival analysis. After treatment, 55 patients showed a normal [18F]‐FDG‐PET scan; 50 of 55 remained in complete remission (CR), with a median follow‐up of 955 d. Only five patients relapsed (median PFS, 296 d). During follow‐up in all five patients, [18F]‐FDG‐PET was the first tool that became positive for relapse. Persistent abnormal [18F]‐FDG uptake was seen in only five patients; all of them relapsed (median PFS, 296 d). In four of five patients, only PET predicted persistent disease. All relapses were proven histologically. Two‐year actuarial PFS rate for negative patients was 91% compared with 0% for positive patients. We concluded that [18F]‐FDG‐PET has an important prognostic role in the post‐treatment evaluation of HD patients.

Positron emission tomography with ( 18 F)FDG for therapy response monitoring in lymphoma patients

Lymphomas are a heterogeneous group of diseases with differing histopathology, clinical behaviour, response to therapy and outcome. Lymphomas are highly sensitive to chemotherapy and radiotherapy, and the recent developments in treatment have considerably improved clinical outcome. However, there is increasing recognition that this has been at the cost of long-term treatment-related effects in a relatively young patient population. Thus, one of the most challenging aspects in the imaging of lymphoma patients is tailoring the intensity of the treatment to the individual patient. This paper reviews recently published data concerning the use of fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) for therapy monitoring in lymphoma patients and highlights the shortcomings and future directions. A temporary strategy for the implementation of [18F]FDG-PET in the management of lymphoma patients is proposed.

Hodgkin lymphoma: Response assessment by Revised International Workshop Criteria

Until recently, response assessment in patients with Hodgkins lymphoma (HL) was primarily performed by computed tomography (CT). Based on CT, International Workshop Criteria (IWC) were developed and widely used. Fluorodeoxyglucose positron emission tomography (FDG-PET) has a higher sensitivity and specificity compared with that of CT, and Revised International Workshop Criteria (IWC + PET) were recently proposed, which combine both imaging techniques. We determined whether these integrated IWC + PET-criteria can more accurately predict outcome compared with IWC-criteria in 56 patients with HL. Of the original 56 patients, nine patients relapsed and 47 are still in remission after a median follow-up of 9 years. Based on IWC-criteria, 15 patients had a complete remission (CR) after chemotherapy, 20 had complete remission unconfirmed (CRu), 19 had partial remission (PR) and two had stable disease (SD). In comparison, by IWC + PET, 47 had CR, seven had PR and two had SD. For IWC, outcome was not significantly different in patients with CR/CRu compared to PR (P = 0.61), while for IWC + PET criteria, time-to-next-treatment was significantly shorter in patients with PR compared to CR (P = 0.01). Therefore, IWC + PET-guidelines provide a more accurate response classification compared with that of IWC-guidelines, and are the preferred method for response assessment in patients with Hodgkins lymphoma.

Aggressive and indolent non-Hodgkin's lymphoma: response assessment by integrated international workshop criteria.

Until recently, response assessment in patients with lymphoma was primarily performed by computed tomography (CT). Based on CT, International Workshop Criteria (IWC) were developed and widely used. Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a more sensitive and specific imaging technique for the detection of residual disease in lymphoma, and Revised Integrated International Workshop Criteria (IWC + PET) were recently proposed by the members of the International Harmonization Project (IHP), which combine both imaging techniques. We determined whether these new IWC + PET-criteria, can more accurately predict outcome compared to IWC-criteria in aggressive and indolent non-Hodgkins lymphoma (NHL), and therefore correlated IWC and IWC + PET response with time-to-next-treatment (TNT) in 69 patients with NHL. We demonstrated that IWC + PET-guidelines are highly recommended over IWC-guidelines for patients with potentially-curable and routinely FDG-avid lymphoma. In contrast, no additional value of IWC + PET was demonstrated in a small group of patients with incurable histological subtypes.

Non-Hodgkin lymphoma: retrospective study on the cost-effectiveness of early treatment response assessment by FDG-PET

PurposeAlthough lymphomas are very chemosensitive, 50% of patients with aggressive non-Hodgkin lymphoma (NHL) are not cured with standard first-line treatment. This consists of six cycles of doxorubicin, vincristine, prednisolone and cyclophosphamide (CHOP), recently complemented with rituximab. Preliminary studies show that PET mid-treatment is a good predictor of the remission status at the end of therapy. As patients with persistent FDG uptake after three cycles are unlikely to gain a complete remission, the remaining three cycles of chemotherapy are useless. We investigated the costs and benefits for the use of PET in this early treatment setting.MethodsWe conceived a model using a conventional arm where patients receive the full regimen of six cycles of CHOP [-rituximab (R)] and an experimental algorithm where patients receive either six cycles (PET response) or only three cycles (PET non-response). Based on a patient sample (2004–2006), we calculated the costs for hospitalisation and treatment. We took into account all costs accrued (including overhead costs). We used a sensitivity analysis by varying the most important parameters.ResultsWith a PET price of 700€ and CHOP price (per cycle) of 1,829€, we can conclude to cost saving of 1,879€ per patient. The PET price can increase up to 2,580€ and the cost for one cycle of CHOP can decrease to 500€ per cycle before cost savings are nil. The percentage of non-responders may be as low as 10%. The implementation of rituximab in first-line therapy only increases benefit (4,900€/pt).ConclusionWe conclude to substantial cost savings if management of NHL patients is based on mid-treatment PET scan. The economical data we used seem to be comparable to those published in other European studies. Implementation of Mabthera in first line only increases cost savings.