Early FDG-PET response–adapted risk stratification and further therapeutic decision-making in lymphoma: will this replace the established prognostic indices and be the standard-of-care in clinical management?
- First Online:
- Cite this article as:
- Basu, S. Eur J Nucl Med Mol Imaging (2009) 36: 2089. doi:10.1007/s00259-009-1296-5
- 57 Views
The central philosophy of the currently evolving clinical management of lymphoma is tailoring and individualizing treatment according to the need of the patient. The first sentence of the text on Prognostic index for Hodgkin's disease according to Hasenclever  outlined by the European Society of Medical Oncology (ESMO) upholds this very important aspect of clinical management of lymphoma: “Predicting the outcome is important to avoid over-treating some patients with Hodgkin's disease, and to identify others in whom standard treatment is likely to fail.” Over the last decade, molecular imaging with FDG-PET has been extensively employed in almost every decision-making step in lymphoma impacting the initial staging, monitoring therapeutic response, restaging, and follow-up of these patients. Of these, the most novel and promising clinical application has been the early monitoring of response to therapy that has opened up a unique opportunity of risk stratification and individualizing further treatment based upon the interim FDG-PET imaging results. This has not only provided the oncologists with a simple, easy-to-adopt as well as reliable basis for deciding the further course of therapy in an individual but also brought about a paradigm shift in the evidence-based approach in the management of lymphoma. Based on this major change, several newer approaches and chemotherapeutic regimens are being been developed [2–9] or being actively tested in various centers across the world [10–14].
The most important strategy for improving the outcome in lymphoma, hence, has been identifying those who can be cured with minimal treatment and reliably differentiating them from those where the standard treatment is doomed to failure and in whom more intensive strategies should be employed from the outset. Early identification of non-responders to primary chemotherapy by FDG-PET imaging is a major advance in the management of lymphoma since these patients can be moved into the salvage schedules utilizing aggressive strategies at an earlier stage. Also, there is now ample evidence that early PET response even after two/three cycles of chemotherapy may predict ultimate outcome; this will enable to identify those who may require less intensive treatment with early good response to PET.
Similar to the Hasenclever index [1, 2] for HL, the international prognostic index score (IPI score) has been described for NHL that identifies five significant risk factors prognostic of overall survival by taking into account factors such as age, stage of disease, performance status, number of extranodal sites, and the presence or absence of an elevated lactate dehydrogenase (LDH). While these indices are used to identify patients who are at low or high risk for disease recurrence with the conventional therapy, it should be understood that the numbers generated are based on a group of individuals with the same qualities and it is possible for an individual doing better or worse than their classified percentages based upon the above parameters.
The recent development of early PET response–adapted (a) risk stratification in Lymphoma and (b) further therapeutic decision-making has given rise to adopting a number of very promising therapeutic approaches based upon interim FDG-PET results. These include (I) omitting radiotherapy for patients with interim PET-negative results , (II) early treatment intensification with BEACOPP (Bleomycin+etoposide+doxorubicin+cyclophosphamide+vincristine+procarbazine+prednisone) in Hodgkin's lymphoma (HL) [11, 12], and (III) early escalation to a more intensive regimen like R-ICE (Rituximab+Ifosfamide+Carboplatin+Etoposide) or Burkitt lymphoma regimen or even high-dose therapy with autologous stem cell transplant (ASCT) in non-Hodgkin's lymphoma (NHL) [11, 13, 14]. Residuum in the mediastinum is common during or following treatment and are quite frequently encountered in mediastinal HL or rarer sclerosing B-cell NHL. A course of radiotherapy (RT) after chemotherapy is the standard practice in this situation. However, late morbidity from mediastinal RT has been increasingly realized: a reduced life expectancy due to treatment-related illness, including increased risk of cardiopulmonary disease and second malignancies in the breast and lung. This implies that many patients are being put at additional risk, a proportion of whom will already be cured without RT. The interim FDG-PET results can play a pivotal role in this setting.
The study by Gallamani et al.  demonstrated that the prognostic value of early FDG-PET completely overshadowed the role of the international prognostic score (IPS), with equally dismal outcomes for patients with PET-positive results regardless of IPS stratification and correspondingly excellent survival for patients with PET-negative results independent of the IPS. With multiple studies [6, 7] demonstrating the promise of early interim FDG-PET findings, a pressing question to the oncology and imaging community is: will that be stronger than the traditional prognostic indices and be the standard of care in the clinical management of lymphoma? The implication of a positive answer is of great importance to the field of oncology worldwide with regard to the future clinical practice in this setting.