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Carcinoma of the Lung and Metastatic Disease of the Central Nervous System

We thank Dr. Austin and colleagues for their comments on our article (1), and we concur that adequately powered randomized trials are warranted to evaluate the efficacy of adjuvant therapy following surgery for subgroups of patients with non–small cell carcinoma (2, 3). This would include patients who are currently classified as stage IB. These studies should focus on patients at higher risk of recurrence and on tumors that are more likely to respond to chemotherapy.

We believe that those most likely to benefit would be younger patients with few comorbidities and with large adenocarcinomas that ideally have a genetic profile indicating increased risk of recurrence along with greater susceptibility to adjuvant therapy (i.e., ERCC-1–negative tumors). Younger patients are less likely to have competing diseases, so the impact of late recurring cancers will be greater than that seen in older patients in whom competing diseases limit life expectancy independent of cancer (1). The up-front risks of adjuvant therapy are warranted in this younger population since they are more likely to realize the long-term benefits in terms of a reduction in late recurrences. Similarly, ERCC-1–negative adenocarcinomas are associated with worse survival than ERCC-1–positive tumors, so the risks of chemotherapy are further warranted due to the higher risk of recurrence (3). Adjuvant therapy with cisplatin-containing regimens has also been shown to be more effective in this subset.

In terms of study design, we agree that it is important that these studies have sufficient power, and we would add that the duration of follow-up should be sufficiently long that differences in late recurrence rates can be detected. Insufficient follow-up may bias such studies toward the null.

David Ost

New York University School of Medicine
New York, New York

FOOTNOTES

Conflict of Interest Statement: D.O. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

1. Ost D, Goldberg J, Rolnitzky L, Rom WN. Survival after surgery in stage IA and IB non–small cell lung cancer. Am J Respir Crit Care Med 2008;177:516–523.[Abstract/Free Full Text]
2. Mujoomdar A, Austin JH, Malhotra R, Powell CA, Pearson GDN, Shiau MC, Raftopoulos H. Clinical predictors of metastatic disease to the brain from non-small cell lung carcinoma: primary tumor size, cell type, and lymph node metastases. Radiology 2007;242:882–888.[Abstract/Free Full Text]
3. Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, et al. DNA Repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 2006;355:983–991.[Abstract/Free Full Text]

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