This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fillet, G. Articles by Bonnet, C. Search for Related Content PubMed Articles by Fillet, G. Articles by Bonnet, C. Social Bookmarking                            What's this?

In Reply

Department of Hematology, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium

We thank Drs Gemici and Salepci for their interest in our study.¹ We are not opponents of adjuvant radiotherapy in aggressive localized non-Hodgkin's lymphoma. In our article, we analyzed the mature data of a trial initiated in 1993 to compare radiotherapy versus nothing after four cycles of chemotherapy.

According to the comments by Gemici and Salepci, primary failures were twice as common in the group assigned to radiotherapy. Indeed primary failures at the end of treatment were observed in 17 (6%) of 295 assessable patients assigned to the combined modality as compared with nine (3%) of 273 patients assigned to cyclophospha-mide, doxorubicin, vincristine, and prednisone (CHOP) alone. However, these values are not statistically significant (P = .16).

As presented in Table 1, there is no significant difference in relapse rate between the two arms. The death rate related to the lymphoma is the same in both groups (24%). Gemici and Salepci are right when they state that more than 10% of the patients allocated to adjuvant radiotherapy did not receive it. As mentioned in Results section of our article, 12 of 299 patients allocated to chemotherapy could not be irradiated because of progression (according to the protocol) or death during CHOP induction and 23 could not receive radiation because of a medical decision by local investigators or refusal of the patients. Such protocol deviations are inescapable in a trial conducted on a multicenter basis and reflect real medical practice. In our opinion, they legitimize the analysis performed on an intention-to-treat basis. Because one might argue that such protocol deviations might have influenced negatively the results of CHOP plus radiotherapy, we performed an as-treated analysis for patients in complete remission at the end of treatment. The as-treated analysis (not included in our article) compares the outcomes of complete response patients who have or have not received radiotherapy. No significant difference is observed in terms of disease-free or overall survival rates (Table 1).

Finally, we know that the addition of anti-CD20 to CHOP improves the results in term of complete response rate, event-free survival, and overall survival, particularly in a subset of elderly patients with a low-risk age-adjusted International prognostic index score.^2,3 In our study, we observed a 5-year overall survival of 72% after 4 cycles of CHOP repeated at 21-day intervals (CHOP 21). By adding rituximab, we hoped for an increase of approximately 15% in survival.³ Thus, taking into account the percentage of deaths related to natural causes in this elderly population, the demonstration of a potential benefit of radiotherapy will be even more difficult to assess in a study including rituximab.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Bonnet C, Fillet G, Mounier N, et al: CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: A study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 25:787-792, 2007[Abstract/Free Full Text]

2. Coiffier B, Lepage E, Brière J, et al: CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:280-282, 2002[Free Full Text]

3. Feugier P, Van Hoof A, Sebban C, et al: Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma : a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 23:4117-4126, 2005[Abstract/Free Full Text]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fillet, G. Articles by Bonnet, C. Search for Related Content PubMed Articles by Fillet, G. Articles by Bonnet, C. Social Bookmarking                            What's this?