Impact of radiation dose and tumor size on large cell lymphoma patients in complete response after integrated CHOP-Bleo-radiation treatment protocol

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J. Radiation Oncology

Pergamon

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Biol. Phys., Vol. 31, No. 1, pp. 193-194, 1995 Copyright 0 1994 Elsevier Science Ltd Printed in the USA. All rights reserved 036@3016/95 $9.50 + .OO

Editorial IMPACT LYMPHOMA

OF RADIATION DOSE AND TUMOR SIZE ON LARGE CELL PATIENTS IN COMPLETE RESPONSE AFTER INTEGRATED CHOPBLEO-RADIATION TREATMENT PROTOCOL JOHN D. EARLE, M.D. Mayo Medical School, Rochester, MN

These quotations highlight the need for carefully defined,

for randomized clinical trials and assists in the definition and values for some of the variables. For non-bulky disease, 30 to < 40 Gy provided 9 1% permanent local control, while r 40 Gy yielded 98%. For bulky disease, corresponding figures were 7 1 and 88%. Many reports establish a worse prognosis for more bulky disease as compared to less bulky, but this study suggests in this subset analysis that increasing the dose from 30 to < 40 Gy to r 40 Gy yields significant improvement in local control and that the improvement is greater for more bulky disease. This is also suggestive, but only suggestive, evidence of efficacy for the addition of radiation. Thus, through subset analysis, this trial provides a strong argument for testing chemotherapy versus chemotherapy plus radiation therapy. Furthermore, the radiotherapy should be 2 40 Gy in 2 Gy fractions or its equivalent. Further analyses of the patterns of failure suggest some improvement if fields include uninvolved nodes and warn that extranodal failures will be frequent. An estimate of the proportion of carefully evaluated Stage I and II patients who do not recur after modern, combined chemotherapy programs is about 75%. An additional, unknown fraction might not fail after the addition of radiation, but this study reveals that - 16% will suffer distant relapses. Additional radiation treatment could not prevent such recurrence and thus, might improve results about 10%. Certainly, complications, treatment costs, and other risks must be balanced against this potential benefit. Data with which to make such decisions

sufficiently

will require clinical trials designed to allow statistically

In this issue, Fuller et al. (1) report on responses in 190 patients and failures in 162 who were complete responders in the original trial that planned four cycles of cyclophosphamide, vincristine, doxorubicin, prednisone, and bleomycin (CHOP-Bleo), 40 Gy to initial sites of involvement, four cycles of CHOP-Bleo and four cycles of cyclophosphamide, vincristine, and prednisone (COP) in stage I-III diffuse large cell lymphoma (DLCL). (The treatment program was an integrated, combined modality treatment and not chemotherapy with consolidation radiation therapy.) Permanent local control four cycles of CHOP-Bleo rates correlated with dose on 40 patients receiving from 30 to < 40 Gy and 118 patients receiving 2 40Gy. The first three and last two sentences of the second paragraph of their introduction deserve emphasis: Effective first-generation combination chemotherapy programs produced a dramatic improvement in prognosis for patients with clinically staged DLCL. Preliminary reports of second- and thirdgeneration regimens were even more encouraging. However,

longer follow-up and repeat studies by oncology groups indicate that at least scme regimens may be less effective than was suggested originally. . . . Some investigators have suggested that adjunctive radiotherapy is not indicated for most patients in the management of DLCL. Others, in an effort to reduce the incidence of local recurrence and possibly improve survival, have added radiotherapy to their chemotherapy programs, particularly for patients with bulky or other unfavorable Stage II presentations. mature controlled,

randomized,

clinical trials.

The bias inevitable in patient referral, selection, stage migration, and differences in management make anything less only suggestive and unconvincing. This report does not bear on the efficacy of the described treatment compared to other treatment. It does provide insight regarding important variables for this particular treatment program. Table 6 displays compelling data supporting the need

significant conclusions. Finally, this paper does not address the value of consolidation radiotherapy. By definition, consolidation radiation follows a treatment program that has rendered patients free of disease. The authors report an integrated, combined modality treatment program in which fully half of the active treatment follows the radiation therapy.

Accepted for publication 13 October 1994. 193

I. J. Radiation Oncology 0 Biology 0 Physics

Volume 31, Number 1, 1995

REFERENCE

1. Fuller, L. M.; Krasin, M. J.; Velasquez,W. S.; Allen, P. K.; McLaughlin, P.; Rodriquez, M. A.; Hagerneister,F. B.; Swan, F., Jr.; Cabanillas,F.; Palmer,J. L.; Cox, J. D. Significanceof tumor sizeand radiation doseto local control

in stageI-II diffuselargecell lymphomatreatedwith DHOPBleo and radiation. Int. J. RadiationOncol. Biol. Phys. 31: 3-l 1; 1994.