| Dose-response analysis for radiotherapy delivered to patients with
intermediate-grade and large-cell immunoblastic lymphomas that have completely responded
to CHOP-based induction chemotherapy Richard B. Wilder The University of Texas M. D. Anderson Cancer Center, Houston, TX, Int JROBP 2001;49:17.
Before the 1980s, Stage I–II, Working Formulation intermediate-grade
(follicular large cell, diffuse small cleaved cell, diffuse mixed small and large cell,
and diffuse large cell) and large-cell immunoblastic lymphomas were mainly treated with
radiotherapy alone. Between 1979 and 1987, 4 randomized trials demonstrated an improvement
in 5-year, disease-free survival with the addition of cyclophosphamide, vincristine, and
prednisone chemotherapy. Doxorubicin was later found to be an active agent giving rise to
the current practice of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
chemotherapy followed by involved field radiotherapy Most of the dose-response analyses of lymphoma in the
literature were performed in the era when patients were treated with radiotherapy alone
Lymphomas arising in the brain or bones are more radioresistant
In the above articles, total doses ranging from 30 to 55 Gy were
typically recommended for gross disease. However, after a complete response to
chemotherapy has been achieved, lower doses may be adequate Stryker
et al. reported that the mean dose that produces local control in patients
treated with radiotherapy alone is 48 Gy versus 37 Gy in patients
treated with chemotherapy and radiotherapy. Kamath et al.
at the University of Florida have reported that 30 Gy is sufficient for lymphomas 6
cm that completely respond to induction chemotherapy. For lymphomas that measure 10
cm or only partially respond to induction chemotherapy, radiotherapy doses 40 Gy
appear to be necessary From September 1988 through December 1996, 294 patients with newly diagnosed, Stage I–IV, intermediate-grade or large-cell immunoblastic lymphomas were enrolled on 2 prospective protocols at the M. D. Anderson Cancer Center. Treatment consisted of CHOP-based chemotherapy with or without involved field radiotherapy. One hundred seventy-two patients, with 178 nodal sites and 87 nonbony, extranodal sites of disease achieved a complete response to 2–6 cycles of chemotherapy and underwent involved field radiotherapy. Total radiation doses ranged from 30.0 to 50.4 Gy (mean ± standard deviation: 39.7 ± 2.5 Gy) over 22–49 days using a daily fraction size of 1.3–2.3 Gy. Because various fraction sizes were delivered, the linear-quadratic model was used to convert total radiation doses to biologically equivalent doses given at 1.8 Gy per fraction (D1.8). Results: The median length of follow-up among survivors was 63 months. Regression tree analysis of nodal sites identified 3 distinct groups: (a) lymphomas 10 cm and D1.8 = 29.1–39.1 Gy; (b) lymphomas 10 cm and D1.8 = 39.2–50.8 Gy; and (c) lymphomas > 10 cm. For nonbony lymphomas that measured < 3.5 cm, low doses of radiation resulted in excellent local control (5-year rates: 96% vs. 97% for D1.8 = 29.1–39.1 Gy vs. D1.8 = 39.2–50.8 Gy; p = 0.610). For 3.5–10.0 cm lymphomas, higher doses of radiation resulted in better local control (5-year rates: 40% versus 98% for D1.8 = 29.1–39.1 Gy versus D1.8 = 39.2–50.8 Gy, p < 0.0001). A narrow dose range (D1.8 = 39.2–40.7 Gy) was delivered to the 8 lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, resulting in a 5-year local control rate of only 70%. There was no difference in local control for nodal versus nonbony, extranodal sites of disease. Conclusion: D1.8 ranging from 29.1 to 39.1 Gy yielded excellent local control for nonbony lymphomas measuring < 3.5 cm that had completely responded to a median of 3 cycles of CHOP-based chemotherapy. D1.8 ranging from 39.2 to 50.8 Gy yielded excellent local control for nonbony lymphomas measuring 3.5–10.0 cm that completely responded to either 3 or 6 cycles of chemotherapy. For nonbony lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, D1.8 ranging from 39.2 to 40.7 Gy yielded suboptimal local control, suggesting that higher doses of radiation are indicated. Radiation therapy after a partial response to CHOP chemotherapy for aggressive lymphomas. Richard B. Wilder, Maria A. Rodriguez, Susan L. Tucker, Chul S. Ha, Mark A. Hess, Fernando F. Cabanillas, James D. Cox. International Journal of Radiation Oncology*Biology*Physics, 50:3 : 743-749 From 1988 through 1996, 294 previously untreated patients with Working Formulation
intermediate-grade or large-cell immunoblastic lymphomas underwent CHOP-based chemotherapy
on 2 consecutive protocols at the M. D. Anderson Cancer Center. Forty-four (15%) of these
patients achieved, based on international working group guidelines, a partial
(50–75%) response (n = 25), or unconfirmed complete (76–99%) |