|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 24, No 35 (December 10), 2006: pp. 5612-5613 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.09.1819
In ReplyWake Forest University, School of Medicine, Winston-Salem, NC
Yale Cancer Center, New Haven, CT
Yale University, New Haven, CT
Robert Wood Johnson Medical School, Piscataway, NJ
Yale University, New Haven, CT
Yale University School of Medicine, New Haven, CT We appreciate the comments from Drs Nasser and Einhorn and believe that several important points merit additional discussion. We feel the need to begin by restating "our report demonstrated that PORT [postoperative radiotherapy] is associated with an increase in survival for N2 patients and a decrease in survival for N0 and N1 patients."1 The respondents state that in our analysis we showed "modern radiation techniques and CT [computed tomography] planning still resulted in a detrimental effect on survival for patients with stage I and II disease. Therefore, one conclusion which is clear is that radiation is detrimental in the postoperative setting for patients with stage I or II disease." We note that (1) the title of our report states "Postoperative radiotherapy for stage II or III non–small-cell lung cancer" and (2) that our methods state "stage I patients were excluded." The respondent's confusion over the patients included in our analysis is likely a simple oversight and not preconceived bias against our analysis. The primary reason we performed this analysis was because of the lack of quality prospective evidence defining the role of PORT. We wanted our analysis to be relevant to assist clinicians with the dilemmas they face on a daily basis until accurate prospective data are available. As we state in our report, we excluded patients who died within 4 months of diagnosis to account for perioperative mortality. Failure to do so would bias our report in favor of PORT. At the request of the editorial staff of the Journal of Clinical Oncology, we performed the analysis regarding disease-specific survival, and we excluded 80 patients who died of unknown causes. This accounted for 1% of the cohort, and as stated in our report, did not affect the results presented. We chose to simply present our analysis and did not make any conclusions not definitively supported by the evidence. We feel that examination of the entire report is necessary to allow clinicians to draw accurate conclusions for use in practice and generate new hypothesis for improved treatment strategies. The purpose of our analysis was not to investigate trends in the use of PORT2 but instead investigate if PORT improved survival. The approach of the majority of the radiotherapy community is to not offer PORT for stage N0/N1 patients unless there are certain high-risk characteristics (ie, chest wall invasion or residual disease). Such information was unavailable within the SEER database. However, we do suspect that such high-risk patients are within out cohort, especially since we only selected N0 patients if they were T3/T4. While the respondents selectively point out that PORT was associated with a decrease in survival for N0/N1 patients, they failed to emphasize two other key points: (1) the disease-specific survival was lower for the patients who received PORT, and (2) the survival curves for N0/N1 patients diverged early. When we evaluate this evidence collectively, we speculate that PORT may be a surrogate for patients with macroscopic disease, thus representing a more aggressive phenotype. In the N2 population, the survival curves diverge after almost 3 years. Such would suggest that the benefit with PORT is a late effect, which is possibly secondary to sterilization of microscopic disease. Intercurrent death was not an end point of this study. We do agree that prior evidence has shown cardiac disease to be the largest source of intercurrent death.3 An analysis investigating the risk of death from cardiac disease associated with PORT and if this has changed with time, has been completed. The report for this analysis has been submitted for publication and is currently under review. We do agree with the respondents that "there is phase III evidence-based medicine that this [adjuvant chemotherapy] will achieve a 5% to 15% actual survival increase." However, we express concern with their interpretation that "given the previously negative US Intergroup trial of adjuvant therapy with concurrent chemoradiotherapy and the multiple positive adjuvant chemotherapy trials (in which either a minority of patients or no patients received PORT), chemotherapy (without concurrent radiation) does represent standard adjuvant therapy." We feel it is important to interpret these trials paying careful attention to critical details; only two of the trials included patients whom we would consider candidates (N2) for PORT. The International Adjuvant Lung trial allowed PORT but did not report the results of PORT outcomes.4 The Adjuvant Navelbine International Trialist Association trial reported PORT outcomes and most interestingly, patients with N2 involvement who received PORT (predetermined by treatment centers), and chemotherapy had a 5-year overall survival of 47% compared with 34% for those who received chemotherapy alone.5 However, after reviewing our report with the insight gained from both the accompanying Editorial6 and the respondents' letter, we have identified one particular flaw. All failed to mandate a prospective adjuvant phase III chemoadjuvant radiation therapy trial. This trial needs to be properly designed with appropriate end points (survival and morbidity) and adequate power. Radiotherapy dose and treatment planning techniques must be the current standard with proper centralized quality assurance of the radiation technique utilized. Failure to do so will not only result in more controversy but also fail to improve the standard of care for lung cancer patients following surgery. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Lally BE, Zelterman D, Colasanto JM, et al: Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the Surveillance, Epidemiology, and End Results database. J Clin Oncol 24:2998-3006, 2006 2. Bekelman JE, Rosenzweig KE, Bach PB, et al: Trends in the use of postoperative radiotherapy for resected non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 66:492-499, 2006[Medline] 3. Wakelee HA, Stephenson P, Keller SM, et al: Post-operative radiotherapy (PORT) or chemoradiotherapy (CPORT) following resection of stages II and IIIA non-small cell lung cancer (NSCLC) does not increase the expected risk of death from intercurrent disease (DID) in Eastern Cooperative Oncology Group (ECOG) trial E3590. Lung Cancer 48:389-397, 2005[CrossRef][Medline] 4. Arriagada R, Bergman B, Dunant A, et al: Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 350:351-360, 2004 5. Douillard JY, Rosell R, De LM, et al: Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): A randomised controlled trial. Lancet Oncol 7:719-727, 2006[CrossRef][Medline] 6. Bonner JA: The role of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma: Seeking to optimize local control and survival while minimizing toxicity. Cancer 86:195-196, 1999[CrossRef][Medline]
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
