Final Report of E1484: CHOP vs CHOP + Radiotherapy (RT) for Limited Stage Diffuse Aggressive Lymphoma

Reviewer: Mary Kara Bucci, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 10, 2001

Presenter: Sandra J. Horning
Presenter's Affiliation: Stanford University
Type of Session: Scientific

Background
The objectives of this study were threefold: to determine the rate of complete response (CR) to, and toxicity of, eight cycles of CHOP chemotherapy; to compare 8 cycles of CHOP with 8 cycles of CHOP + involved field radiotherapy (IFRT), with respect to duration of response, survival, toxicities, and sites of relapse; to determine the ability of IFRT to convert non-responders to complete responders.

Materials and Methods

352 patients with limited stage diffuse aggressive lymphoma were randomized to receive CHOP x 8 or CHOP x 8 + IFRT, 30Gy, for complete responders. Patient from both arms who achieved only a partial response received 40 Gy IFRT.

Eligible patients had bulky Stage I, Stage IE, or Stage II diffuse aggressive lymphoma.

69% of pts had Stage II/IIE disease, 82% were large cell histology, 24% had B symptoms, median age = 59.

Results

Complete response (CR) and partial response (PR) to 8 cycles of CHOP were 61% and 28%, respectively.

28% of patients with a PR who received 40 Gy converted to a CR.

In an intent-to-treat analysis, 2-, 5-, and 10-year disease-free survivals were 83%, 74%, and 57% for the IFRT arm and 68%, 56%, and 46% for the chemo alone arm (p=.04).

Overall Survival (OS) in the intent to treat analysis at 5-, 10-, and 15- years was 87%, 68%, and 60% for the IFRT arm and 73%, 68%, and 44% for the CHOP only arm (p=.24).

In an as-treated analysis, DFS (p=.05)and TTP (p=.06) were borderline significant in favor of the IFRT arm.

10-year disease-specific survival (DSS) was 81% for both arms.

In the as-treated analysys, 15/31 relapses in the CHOP only arm occurred in sites of prior disease, compared to 3/17 in the IFRT arm.

Author's Conclusions

CHOP chemotherapy was well-tolerated.

CHOP + IFRT showed improved DFS and TTP when compared to CHOP alone.

There was no significant change in overall survival between the two groups, perhaps because the small number of patients did not power this study to detect a small change.

Patterns of failure were different between the two groups, with fewer patients in the IFRT arm having recurrence in a site of previous disease.

Clinical/Scientific Implications
Low dose IFRT provides excellent local control even at 15 years. This study demonstrates the benefit of IFRT with regard to local control. Patients who achieve a PR with CHOP only can be converted to a CR with the addition of involved-field radiotherapy. The benefit of IFRT with regard to TTP and FFS is of borderline significance.

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