Evidence (Albeit Modest) of Improved Survival for AR Lymphoma Patients over the Last Quarter Center
Evidence (Albeit Modest) of Improved Survival for AR Lymphoma Patients over the Last Quarter Center
Abstract & Commentary
By William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC and is Editor of Clinical Oncology Alert. Dr. Ershler is on the speaker’s bureau for Amgen and does research for Ortho Biotech.
Synopsis: Although remissions have been more frequent and treatments more aggressive, there are little data in the literature that overall survival for follicular lymphoma has been improved. Examination of the SEER database, however, clearly demonstrates that over the last quarter century, overall survival for follicular lymphoma patients has improved. Explanations could include the sequential application of more effective therapies and/or improvement in supportive care.
Source: Swenson WT, et al. Improved survival of follicular lymphoma patients in the United States. J Clin Oncol. 2005;23:5019-5026.
Over the past 2 decades, new treatment strategies have been developed for patients diagnosed with follicular lymphoma. With greater availability of new and effective therapies, it has not been difficult to demonstrate improved tumor response, in terms of remission rate and even remission duration. However, improved survival has not been unequivocally demonstrated.
Swenson and colleagues at the University of Iowa have queried the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database to get at this question. They obtained survival data for 14,564 patients diagnosed with follicular lymphoma (FL) between 1978 and 1999 from the 2002 SEER registry. This national registry derives data from a number of geographically diverse locales within the United States and provides an excellent resource for epidemiological studies.
After stringent exclusionary criteria were applied, 8788 patients were identified for extensive multivariate analysis. The patients were first divided into 4 sub-groups based on year of diagnosis: 1978 to 1985, 1986 to 1992, and 1993 to 1999, and then subsequently divided into 2 groups from 1983 to 1989 and 1990 to 1999 as more accurate staging data became available in 1983.
This analysis involved calculations using observed median survival times, Kaplan-Meier survival curves, proportional death hazard ratios, and relative survival rates. The trends in annual adjusted death hazard ratios were analyzed using Joinpoint regression. Among patients with stage-specific data, the median survival time improved from 84 months in 1983 to 1989 to 93 months in the 1993 to 1999 era. Thus, there was an 11 percent improvement in overall survival for follicular lymphoma patients in the last quarter of the 20th century.
Commentary
Advances in overall survival are difficult to demonstrate when the natural history of a disease is indolent and survival relatively long. A notable exception occurs when a highly effective new therapy is introduced, such as imatinib mesylate for chronic myelogenous leukemia (discussed next in this issue of Clinical Oncology Alert). No such dramatic advances have been made in the treatment of follicular lymphoma, although new drugs and drug combinations, refined radiotherapy technology and innovative, aggressive approaches (eg, auto- and allogeneic stem cell or marrow transplants) for selected cases have certainly improved responses and response durations. Furthermore, more effective supportive care including better antibiotics, growth factors and antiemetics and analgesics have reduced adverse consequences and allowed the administration of more intensive therapy without prohibitive impact on quality of life. Thus, the findings from the SEER database should come as no surprise and provide some reassurance that the field is moving in the right direction.
A cynic might point to the fact that it took a large database of greater than 14,000 patients to demonstrate any difference in survival, and this was only modest (less than a year improvement in overall survival over a 25- year span). Furthermore, the survival gain might be due to an increased effort to diagnose earlier (lead-time artifact). Yet, this was a rigorous and careful analysis, and as mentioned above, the disease is chronic, heterogeneous and with relatively long survival, even at the beginning of the evaluation period. In fact, as pointed out in the accompanying editorial,1 the largest increment in survival enhancement probably occurred in the preceding quarter century when radiotherapy and systemic chemotherapy were first applied. Furthermore, in 2 reports published in abstract form, similar survival improvement was demonstrated in smaller studies, one from a single institution and another from a cooperative group.
Although there has been a modest improvement in survival, the disease remains, for the most part, incurable. Examination of the survival curves sprinkled throughout the article leaves the clear impression of a missing plateau. Perhaps in the modern era in which targeted therapies are being developed at a rapid pace and older therapies are being reconfigured into new and more logical combinations, the next quarter century will witness the appearance of a plateau in survival and a more robust demonstration of improved overall survival.
Reference
1. Lister TA. Improved survival for patients with follicular lymphoma. J Clin Oncol. 2005;23:4830-4831.
Although remissions have been more frequent and treatments more aggressive, there are little data in the literature that overall survival for follicular lymphoma has been improved. Examination of the SEER database, however, clearly demonstrates that over the last quarter century, overall survival for follicular lymphoma patients has improved. Explanations could include the sequential application of more effective therapies and/or improvement in supportive care.Subscribe Now for Access
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