|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Originally published as JCO Early Release 10.1200/JCO.2005.03.911 on June 27 2005 © 2005 American Society of Clinical Oncology.
Improved Survival for Patients With Follicular LymphomaSt Bartholomew's Hospital, London, United Kingdom It is claimed by Swenson et al1 in this issue that survival for patients with follicular lymphoma improved during the last quarter of the last century. Despite the fact that the improvement is modest, this observation is intriguing, particularly considering similar results from both a single center2 and a cooperative group3 presented during this past year. The findings should be considered in light of our previous knowledge of the natural history of this disease and the impact on it of both irradiation and chemotherapy. There is a relative paucity of information about the natural history of follicular lymphoma because a large proportion of patients, even in the earliest series, received at least irradiation at some point. However, it is undoubtedly a relatively indolent condition in which spontaneous regression may occur and in which, in a proportion of patients, progression may be slow.4-11 Transformation to a more aggressive histologic type may occur and usually carries a poor prognosis. The clinical course of the disease (ie, the natural history modified by therapy) in the 20th century was largely that of a remitting recurring disease, with death usually resulting from the illness after several years. Responsiveness to therapy was the rule rather than the exception, with responders living longer than nonresponders but cure being rare. The median survival, which was reported in large series from major centers during the time when irradiation was almost the only treatment, was 5 years.5,6 Subsequently, with the demonstration of the potential role of chlorambucil,12 chemotherapy became the treatment of choice for advanced disease at the initial presentation, with irradiation reserved for local or locoregional disease. In the setting of trials of initial therapy designed to test the curability of the disease (which failed) with alkylating agent–based combinations with or without anthracyclines and re-treatment at recurrence (usually with chemotherapy), it was established that the median survival time was approximately 10 years, with the average patient having had three episodes of therapy at approximately 3-year intervals.13 Thus, it might be argued that between the mid-1960s and the mid-1980s, chemotherapy had led to a doubling of the median survival time, even if resulting in few cures. In their article, Swenson et al1 present the outcome for several thousand patients with follicular lymphoma reported from nine population-based Surveillance, Epidemiology, and End Results cancer registries between 1978 and 1999. Attractively, the results are not only presented in terms of overall survival of cohorts of patients in sequential time periods, but they are also presented in terms of reduction in the risk of dying relative to the normal population. Detailed analysis of a subset of patients for whom staging was considered adequate suggests that the improvement occurs mainly in patients presenting with advanced disease. What were the differences in the management of follicular lymphoma between the 1970s and the 1990s that could account for an improvement, albeit of less than a year, in survival? One possibility that was not considered is that, with increasing awareness of the curability of some types of lymphoma, painless adenopathy, which might otherwise have been ignored, might have been brought to the attention of the physician and, thus, the diagnosis made sooner, giving a lead time effect. If, as is likely, this is not the case and the improvement is real, what is new? Without doubt, newer chemotherapy regimens, including drugs such as fludarabine, are effective when alkylating agent–based treatments fail. Newer regimens have resulted in high complete remission rates with longer progression-free survival from first-line therapy and have also attained molecular remissions, which may confer a survival advantage. Myeloablative consolidation therapy of second remission induces long responses and, in a small randomized trial,14 resulted in an improvement in overall survival. Interferon alone induces remissions and, in a meta-analysis, has been shown to improve overall survival when combined with moderately intensive chemotherapy.15 Antibody therapy alone will also induce remissions and is showing dramatic improvement in at least progression-free survival when combined with several chemotherapy regimens. Allogeneic hematopoietic stem-cell transplantation, which is only applicable to a small minority of patients, may actually be curative. Most, if not all, of these treatments were not being used before 1990, and all of these treatments either induce remission in at least 50% of patients or prolong remission, when other treatments have failed. Because responsiveness confers a survival advantage and it may be possible to induce more remissions with a larger therapeutic armamentarium, it seems quite plausible that the authors' conclusions are correct. It is appealing that second-, third-, and maybe fourth-line therapy may be shown to have an effect on overall survival of a remitting, recurring disease. It should not detract our attention from making every effort to capitalize on our rapidly increasing understanding of the pathogenesis of follicular lymphoma to develop curative therapy that will lead to unequivocal improvements in survival. Author's Disclosures of Potential Conflicts of Interest The author indicated no potential conflicts of interest. REFERENCES
1. Swenson WT, Wooldridge JE, Lynch CF, et al: Improved survival of follicular lymphoma patients in the United States. J Clin Oncol 23: 5019-5026, 2005 2. Lui Q, Fayad L, Hagmeister FB, et al: Stage IV indolent lymphoma: 25 years of treatment progress. Blood 102: 398a, 2003 (abstr 1446) 3. Fisher RI, LeBlanc M, Press OW, et al: New treatment options have changed the natural history of follicular lymphoma. Blood 104: 168a, 2004 (abstr) 4. Symmers D: Giant follicular lymphadenopathy with or without splenomegaly. Arch Pathol 26: 603-647, 1938 5. Gall EA, Mallor TB: Malignant lymphoma: A clinicopathological survey of 618 cases. Am J Pathol 18: 381-415, 1942 6. Rosenberg SA, Diamond HD, Craver LF: Lymphosarcoma: Survival and the effects of therapy. Am J Roentgenol Radium Ther Nucl Med 85: 521-532, 1961[Medline] 7. Jones SE, Fuks Z, Bull M, et al: Non-Hodgkin's lymphoma: IV. Clinicopathologic correlation in 405 cases. Cancer 31: 806-823, 1973[CrossRef][Medline]
8. Brice P, Bastion Y, Lepage E, et al: Comparison in low-tumour-burden follicular lymphomas between an initial no treatment policy, prednimustine or interferon-alpha: A randomised study from the Groupe d'Etude des Lymphomas Folliculaires. J Clin Oncol 15: 1110-1117, 1997 9. Young R, Longo D, Glatstein E, et al: Watchful waiting vs aggressive combine modality treatment. Semin Hematol 25: 11-6, 1988 (2 suppl 2)[Medline]
10. Advani R, Rosenberg S, Horning S: Stage I and II follicular non-Hodgkin's lymphoma: Long-term follow-up of no initial therapy. J Clin Oncol, 22: 1454-1459, 2004 11. Ardeshna KM, Smith P, Norton A, et al: Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced stage non-Hodgkin's lymphoma: A randomised controlled trial. Lancet 362: 516-522, 2003[CrossRef][Medline] 12. Galton DAG, Israels LG, Nabarro JDN, et al: Clinical trial of p(di-chloroethylamino) phenylbutyric acid (CB 1348) in malignant lymphoma. BMJ 2: 1172-1176, 1955
13. Gallagher CJ, Gregory WM, Jones AE, et al: Follicular lymphoma: Prognostic factors for response and survival. J Clin Oncol 4: 1470-1480, 1986
14. Schouten HC, Qianm W, Kvaloym S, et al: High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin’s lymphoma: Results from the randomised European CUP trial. J Clin Oncol 21: 3918-3927, 2003
15. Rohatiner AZS, Gregory WM, Peterson B, et al: Meta-analysis to evaluate the role of interferon in follicular lymphoma. J Clin Oncol 23: 2215-2223, 2005
Related Article
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
