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

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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.

    Oncolink's ASH Coverage made possible by an unrestricted Educational Grant from Amgen.



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