Radiation therapy versus radiation therapy plus chemotherapy

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Clinical trials of limited stage HL have more recently focused on the use of radiation therapy versus combined radiation therapy and chemotherapy. Decades ago, the specific chemotherapy regimen usually employed was MOPP. Given that MOPP has been replaced in the treatment of HL by ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine), these pioneering studies are of only moderate relevance to today's practice. As a general statement, these studies included both pathologically staged and clinically staged patients, and generally compared subtotal lym-phoid radiation therapy or total lymphoid radiation therapy versus MOPP (or a variant of MOPP) combined with limited or extended field radiation therapy. Table 73.2 shows a summary of these studies. Two studies found an advantage (FFR) in combined modality therapy (CMT), whereas the others did not. There was no difference in OS in any study. Other findings of studies of this era are important. Multiple sites of disease were associated with less favorable outcome.8 Several studies

Table 73.2 Selected early trials of extended radiation therapy versus extended radiation therapy + chemotherapy in early stage HL

Author Ref. Year Comment

Jones 6 1982 PS I-II involved field

XRT + MOPP vs extended field XRT—trend toward improved RFS with combined therapy (P = 0.12). No difference in OS. Predominant RFS effect on those patients with B symptoms (P < 0.03)

Nissen 7 1982 PS I-II randomized to extended field XRT or mantle XRT + MOPP. RFS better with combined therapy (P < 0.05). No difference in OS

Rosenberg 3 1985 PS IA—IIB Randomized to

IF XRT + MOPP vs extended field XRT. Combined better RFS but no difference in OS. PS IB- IIB TLI + MOPP vs TLI. No difference in RFS or OS

Tubiana 8 1989 PS I-II Randomized to

MOPP + extended field XRT vs TLI DFS better in combined therapy, but no difference in OS

PS, pathologic stage; XRT, radiation therapy; IF, involved field; TLI, total lymphoid irradiation.

also concluded that large mediastinal masses (LMMs) were an adverse prognostic sign. In particular, patients with bulky mediastinal masses treated with radiation therapy alone had a high incidence of disease relapse, and most of these studies recommended CMT for this group of patients.9-14

An additional early trial used a different approach, as patients with limited stage HL were randomized to chemotherapy with cyclophosphamide, vinblastine, procabazine, and prednisone (CVPP) alone or CVPP plus IFRT. The study found no differences in relapse-free survival (RFS) or OS. Additional prognostic factors were age more than 45 years and more than two lymph node areas involved with HL, as well as bulky disease.15

A meta-analysis of 3500 patients treated on randomized trials of more versus less extensive radiation therapy and trials comparing radiation therapy plus chemotherapy to radiation therapy alone was published in 1998.16 Adding chemotherapy reduced the risk of recurrence by 50% but did not improve OS. This was felt to be a result of an ability to salvage radiation therapy failures with subsequent chemotherapy.

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