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Ann Thorac Surg 2003;76:979
© 2003 The Society of Thoracic Surgeons
a Department of Radiation Oncology Klinikum , rechts der Isar, Technical University Munich, Ismaninger, Strasse 22 D-81675, Munich, Germany
e-mail: bjeremic{at}lrz.tu-muenchen.de
To the Editor:
In the article by Cyjon and associates [1], induction chemotherapy (CHT) followed by chemoradiotherapy (CHT+RT) and surgical intervention in locally advanced non–small cell lung cancer achieved a median survival time of 16 months and a 3-year survival rate of 22%. The authors provided only survival data and not relapse-free survival data. Therefore, on the basis of statements such as "the pathologic specimen showed no evidence of residual tumor in 5 patients" and "at the time of analysis, 16 patients were alive, 9 of them with no evidence of disease," we are left with between 5 (9%) and 9 (16%) potential long-term survivors. This is an important issue, as these patients are at risk for the development of distant metastases, which would decrease overall results with further follow-up. Also, there was an 11% total mortality rate and substantial toxicity (grades III and IV neutropenia, 61% of patients, and grades III and IV anemia, 18% of patients). Such were the results in achieving no evidence of residual tumor in the pathologic specimens of 5 patients (9% of all patients and 17% of patients having complete resection. The latter (the better) figure is identical to that obtained using induction CHT followed by RT without operation as reported in a French multiinstitutional study [2], which also had much less toxicity.
Another option in these patients is exclusive concurrent CHT+RT, which is superior to RT alone [3, 4] or induction CHT followed by RT [5]. Although CHT+RT is frequently considered too toxic, in various prospective, randomized phase III trials, toxicity was largely dependent on CHT administration [3, 4, 6, 7]. Toxicity was very low with concurrent low-dose daily CHT (no grade 5 toxicity, and infrequent acute and late grade 3 or 4 toxicity [3, 4]. Many consider exclusive concurrent CHT+RT the standard treatment of patients with locally advanced non–small cell lung cancer. This therapy offers median survival times of 20 months or more and 5-year survival rates of 20% or higher [4–6], and provides a target with which to compare various current and future therapies.
Finally, Cyjon and co-workers, like others, believe the theoretical advantages of induction CHT to be (1) a reduction in local-regional tumor burden and (2) a lower systemic failure rate as a result of the increased chemosensitivity of micrometastases, which may have a faster growth rate and a higher proportion of cells in the S phase. Note that points 1 and 2 are in sharp contrast! If the log cell-killing nature of RT and CHT is correct, then point 2 is easier to achieve. The completely opposite situation (again theoretically) pertain at the local-regional level a bigger tumor burden and therefore less chemosensitivity, ie, increased chemoresistance, a slower growth rate, and a lower proportion of cells in the S phase). Therefore, point 1 becomes an impossible goal to achieve. Indeed, induction CHT followed by RT led to a lower rate of systemic failures (not local-regional ones) and improved survival compared with RT alone [2].
References
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