Reduction of fatal complications from combined modality therapy in Hodgkin's disease

A total of 464 pathologically staged IA through IIIB Hodgkin's disease patients were evaluated for the risk of developing acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, or a fatal infection after treatment with radiation therapy (RT) alone, initial combined radiation therapy and chemotherapy (CMT), or RT with MOPP administered at relapse. Patients received a standard six cycles of MOPP, and additional maintenance chemotherapy was not administered. Patients receiving total nodal irradiation (TNI) and MOPP chemotherapy have an 11.9% actuarial risk of developing a fatal complication at ten years, as compared to a 0.8% risk for lesser field irradiation and MOPP (P = .005). The risk with RT alone is 0.6%. Patients 40 years of age or older have a greater risk for complications. These data report a low risk for fatal complication with CMT when less than TNI is administered and when maintenance chemotherapy is not used.     

Treatment selection for stage IIIA Hodgkin's disease patients

Two treatment policies for the therapy of patients with Stage IIIA Hodgkin's disease are compared. From 1969-1976, 49 newly diagnosed and pathologically staged IIIA patients received total nodal irradiation (TNI) alone (no liver irradiation). Although actuarial survival was 80% at 5 years and 68% at 10 years, actuarial freedom from relapse was only 38% at 5 years. Accordingly, a new treatment policy was instituted in 1976. Patients with either CS IIIA disease, multiple splenic nodules, IIIA with a large mediastinal mass or III2, received combined modality therapy (combination chemotherapy and irradiation). All others received TNI. Thirty-six patients have been treated under the new program. The actuarial survival is 90% at 5 years and the relapse-free survival is 87%, suggesting the superiority of this approach.     

An evaluation of total nodal irradiation as treatment for stage III A Hodgkin's disease.

Between April 1969 and December 1974, 37 patients with surgically staged III A Hodgkin's disease were treated with total nodal irradiation (TNI). Their probability of relapse-free survival at 7 years is 51% and overall survival 82% with the majority of patients remaining disease free after retreatment with MOPP (10 of 16). In contrast, 21 stage III B patients treated with TNI and MOPP chemotherapy over the same time period have a relapse-free survival of 74% and overall survival of 91%. Because of superior results in treating stage III B patients with combined modality treatment, we fell that a relapse-free survival of 51% may not justify continuation of TNI as the only modality of treatment for patients with stage III A disease, and we have initiated a trial of combined radiation therapy and MOPP chemotherapy in these patients. The most effective treatment of stage III A Hodgkin's disease, however, remains uncertain and depends both on the ultimate risk of combined modality treatment and the success of retreatment following relapse after radiation.     

Four cycles of chemotherapy and regional radiation therapy for clinical early-stage and intermediate-stage Hodgkin's disease.

To achieve a high percentage of durable complete remissions (CR) and prolonged survivals and reduce toxicity in patients with early-stage and intermediate-stage Hodgkin's disease, a randomized trial of four cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) versus four cycles of thiotepa, bleomycin, and vinblastine (TBV) combined with regional radiation therapy (RT) was conducted. For MOPP and RT, the CR percentage was 98% (60 of 61), and at 5 years, the percentage of patients in CR was 90%, with freedom from progression of 89% and overall survival of 91%. For TBV and RT, the CR percentage was 93% (55 of 59), with a 5-year duration of CR of 83%, freedom from progression of 81%, and overall survival of 91% (P greater than 0.15). The median follow-up was 65 months (range, 7 to 96 months). For 27 patients with clinical Stage IIIA, the CR percentage for MOPP and RT was 75% (12 of 16), with 1 relapse and 4 deaths. For TBV and RT, the CR percentage for clinical Stage IIIA was 73% (8 of 11) with 2 relapses and 2 deaths. Short-term toxicity except for transient leukopenia was less for TBV and RT than for MOPP and RT. Good results are achievable with combined treatment without excessive toxicity.     

Radiation therapy for pathologic stage III Hodgkin's disease with and without chemotherapy

Ninety-eight patients with pathological Stage (PS) III Hodgkin's disease treated between 1969 and 1984 were retrospectively analyzed. Treatment consisted of radiation therapy (RT) alone in 46 patients and combined radiation therapy and chemotherapy (CMT) in 52 patients. The median follow-up was 10 years (range 3-19 years). Fifteen-year year survival for patients with Stage III1-is better than for Stage III2 patients (82% vs 53%; p = .014). Patients with Stage III1A have a favorable prognosis regardless of treatment modality. The probability of freedom from relapse at 15 years for patients with pathological Stage III1A treated with radiation therapy is 70%, compared to 83% for pathological Stage III1A patients treated with combined modality therapy (p = .56). In patients with pathological Stage III2A, III1B, and III2B relapses were less frequent with the use of combined modality therapy compared to radiation therapy. We conclude that pathological Stage III1A patients may be treated with radiation therapy alone; the other subsets of patients benefit from combined radiation and chemotherapy.     

Radiation therapy versus combination chemotherapy in the treatment of early-stage Hodgkin's disease: seven-year results of a prospective randomized trial

The study population included 136 patients with stage IA, IB, IIA, IIB, or IIIA1 Hodgkin's disease. The median follow-up is 7.5 years. Among the 30 patients with peripheral IA disease, all patients achieved a complete response (CR) with radiation therapy, and no patient has relapsed. Patients of other stages were randomized to receive radiation therapy or mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Among the 51 patients randomized to receive radiation therapy, 49 (96%) achieved complete remission, 17 (35%) have relapsed, and 10 (20%) have died. Fifty-two of the 54 (96%) assessable patients randomized to receive MOPP obtained CRs, seven (13%) have relapsed, and four (7%) have died. The projected 10-year disease-free survival of patients randomized to receive radiation therapy is 60%; for those randomized to receive MOPP, it is 86% (P2 = .009 in favor of MOPP). The projected 10-year overall survival for patients randomized to radiation therapy is 76%, and for MOPP-treated patients it is 92% (P2 = .051 in favor of MOPP). When the randomized patients with massive mediastinal disease or stage IIIA1 disease were excluded from the analysis, the disease-free (67% for radiation v 82% for MOPP) and overall survival (85% for radiation v 90% for MOPP) were not significantly different between the two arms. Subset analysis showed significant superiority of MOPP in the treatment of the following patient groups: stage IIIA1 or massive mediastinal disease, no B symptoms, initial erythrocyte sedimentation rate greater than 20 mm, four or more sites of disease, and younger than age 40 years. Preliminary analysis of this ongoing study shows that MOPP chemotherapy is at least as effective as radiation therapy in the treatment of the specific groups of early-stage Hodgkin's disease patients randomized. The final assessment of these two diverse treatment options will depend largely on the long-term survival and the incidence of early- and late-treatment complications for which patients are continuing to be observed.     

Treatment of pathologically staged IIIA Hodgkin's disease

We have reviewed the records of 37 patients with pathologically staged IIIA Hodgkin's disease, treated from 1970 to 1982. Twenty patients were staged IIIA1 and 17 staged IIIA2. Treatment consisted of total nodal irradiation in 33 patients (eight of whom received adjuvant MOPP), and mantle plus para-aortic irradiation in four patients (all of whom received adjuvant MOPP). Five-year relapse-free survival (RFS) in patients without splenic involvement was 77% versus 49% for those with splenic involvement (p = 0.43). Five-year RFS in patients treated with irradiation and chemotherapy (RT/CT) was 76% vs. 47% for patients treated with irradiation alone (p = 0.12). RFS was not influenced by sex, mediastinal involvement by tumor, or anatomic substage. Overall survival (corrected for deaths due to intercurrent disease) for the entire group of patients was 92% at 5 years and 87% at 10 years. Sex, mediastinal or splenic involvement by tumor, therapy (RT vs. RT/CT), or anatomic substage did not significantly influence survival. We currently recommend RT/CT only for those patients with extensive splenic involvement and/or Stage IIIA2 disease. We feel that the poor prognosis of these patients justifies the use of RT/CT and its risk of second malignancies.     

Clinical stages I and II Hodgkin's disease: a specifically tailored therapy according to prognostic factors

The H5 program in clinical stage (CS) I to II supradiaphragmatic Hodgkin's disease (HD) was tailored to prognostic factors identified in former European Organization for the Research and Treatment of Cancer (EORTC) studies. Among the 494 adult patients included in the study, the 237 patients belonging to the favorable group (H5F) underwent a staging laparotomy (Sx) in order to select the patients who could be treated with limited radiotherapy (RT) only. Thus, 198 patients (84%) with negative laparotomy were treated with RT alone and randomized to either mantle irradiation (M) or extended field mantle plus para-aortic (M + PA) irradiation. Complete remission (CR) was achieved in 99% of the patients. There was no difference in the 6-year relapse-free survival (RFS) rate (74% and 72%, respectively) or survival rate (96% and 89%). Therefore, Sx helped to define those patients who could be treated with M alone in contrast to those who required more aggressive therapy. The 39 patients with positive laparotomy were treated as the unfavorable group (H5U) from onset and randomized to either total/subtotal nodal irradiation (TNI/STNI) or a sandwiched mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) X 3, M irradiation, MOPP X 3 protocol (3M). Although the RFS rate was higher in the 3M arm (100% v 53%; P = .002), the 6-year survival was not significantly different between the two arms (overall, 92%). In the 257 patients with initial unfavorable disease, the Sx was avoided. They were randomized to either TNI/STNI or 3M. In complete responders (96%), the 6-year RFS was 91% in the 3M arm and 77% in the TNI/STNI arm (P = .02). The pattern of failure differed in the two arms: the inverted Y and spleen irradiation controlled occult infradiaphragmatic disease better than MOPP; conversely, less patients begun on MOPP recurred in the involved mantle areas. The difference in 6-year actuarial total survival (TS) (89% and 82%; P = .05 in favor of the 3M arm) was not retrieved after exclusion of the unrelated deaths from the analysis. The two arms produced similar TS in patients under 40 years of age. TNI retains interest, especially in young men wishing to preserve fertility. The overall result shows that when treatment is tailored to initial prognostic factors, excellent results can be obtained in all patient subgroups at minimal morbidity and toxic cost.     

Lack of apparent difference in outcome between clinically staged IIIA and IIIB non-small-cell lung cancer treated with radiation therapy

The current American Joint Committee on Cancer (AJCC) staging system for bronchogenic carcinoma, which divides stage III M0 cases into stages IIIA and IIIB, is based on the observation that selected patients with IIIA disease (T3 or N2) can undergo complete surgical resection, in distinction to IIIB patients (T4 or N3). To understand the value of this system when applied to clinically staged (CS) patients treated with a standard nonoperative approach, the records of patients with squamous cell, large-cell, and adenocarcinoma of the lung treated with radiation therapy (RT) at the Fox Chase Cancer Center from 1978 to 1987 were reviewed. Three hundred sixteen patients were identified as having CS III M0 disease treated with single daily fraction RT without chemotherapy or sensitizers. Of these, the distinction between IIIA (166) and IIIB (140) could be made for 306 patients. The median survival time (MST) for all CS III patients was 9.6 months, and the 2-year survival was 17%. No difference was observed in MST between CS IIIA and IIIB patients (9.4 v 9.8 months, P = .78), in 2-year survival (17% v 18%), or in rate of first failure within the RT field (43% v 44%). MSTs for the 157 CS IIIA and IIIB patients with less than 5% weight loss and Zubrod performance status (PS) 0 to 1 were 13.0 and 15.8 months (P = .29), respectively. This lack of difference in outcome for CS IIIA and IIIB patients receiving RT has important implications in the design and stratification of future nonoperative trials for stage III lung cancer.     

The therapeutic implications of splenic involvement in stage IIIA Hodgkin's disease.

In an effort to determine the most appropriate initial therapy for patients with stage IIIA Hodgkin's disease, a comparative analysis was undertaken of 13 pathologically staged IIIA Hodgkin's disease patients whose abdominal disease was localized to the spleen (IIIsA); 17 IIIA patients with spleen and abdominal lymph node involvement (IIIs+n+A) and 44 stage IIA patients. The three groups were treated concurrently with either extended field irradiation alone or limited field irradiation followed by MOPP chemotherapy. Relapse rates after irradiation alone were 17% for the IIIsA patients; 63% for the IIIs+n+A patients and 25% for the stage IIA patients. Following therapy with irradiation and chemotherapy no relapses occurred among the IIIsA and IIIs+n+A patients while 2/16 (13%) stage IIA patients relapsed. After irradiation alone stage IIIs+n+A patients had a significantly shorter remission duration and survival than the stage IIA patients (p = 0.03 and 0.002, respectively) but remission duration and survival were similar for the IIIsA and IIA patients. When therapy was irradiation and chemotherapy no significant differences in remission duration or survival were noted for the three groups. The most common sites of relapse for the IIIs+n+A patients were extralymphatic (60%) while no extralymphatic relapse have occurred among the IIIA patients (p less than 0.02). The only relapse among the IIIsA patients was at an extralymphatic site. These data have shown that patients with IIIsA Hodgkin's disease have a similar prognosis to stage IIIA disease but after therapy with irradiation along stage IIIs+n+A patients have a poorer prognosis. Combined irradiation and chemotherapy should, therefore, be considered for stage IIIs+n+A Hodgkin's disease when abdominal nodal disease cannot be included in the initial radiation port.     

Stages IIB and IIIB Hodgkin's disease. Results of combined modality treatment.

Between April 1969, and December 1974, 23 IIB and 26 IIIB surgically staged patients with Hodgkin's disease were treated at the Joint Center for Radiation Therapy. Stage IIB patients received either mantle and para-aortic-splenic pedicle, or total modal irradiation (TNI) alone or with the addition of combination chemotherapy. Relapse-free survival is 83% and overall survival 88%. Eleven patients received combination chemotherapy in addition to mantle and para-aortic irradiation, and both the relapse-free and overall survival are 100%. Of the stage IIIB patients, seven received TNI alone with four relapses, and 19 were treated with TNI and MOPP with two relapses. These relapse rates are significantly different (p less than 0.05). The relapse-free and overall survival for all stage IIIB patients is 66% and 84% respectively. These data imply that irradiation alone is not adequate treatment for stage IIIB Hodgkin's disease, and that with the addition of combination chemotherapy both the disease-free and overall survival is similar to that of early stage Hodgkin's disease without systemic symptoms. The ideal management of stage IIB Hodgkin's disease is less certain; it is our plan to study the efficacy of combined modality treatment.     

Two cycles of MOPP and radiotherapy for stage III1A and stage III1B Hodgkin's disease

One hundred two adult patients with stage III1A (76 patients) and stage III1B (26 patients) Hodgkin's disease were treated with two cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and radiotherapy (XRT) between 1970 and 1984. Sixty-four of the patients were treated between 1970 and 1978 with two cycles of MOPP and XRT to the mantle, upper abdomen, and pelvis. The remaining 38 patients were treated from 1978 to 1984 with a modification of the protocol in which pelvic XRT was omitted and low-dose whole-lung XRT was administered to patients with unfavorable mediastinal disease. The 10-year actuarial freedom-from-progression (FFP) and determinate survival rates at a mean follow-up of 93 months were 84% and 86% for stage III1 disease, 86% and 84% for stage III1A disease, and 78% and 91% for stage III1B disease. Three patients died of treatment-related toxicities without evidence of Hodgkin's disease, two died of complications of myelosuppression and one of acute nonlymphocytic leukemia (ANLL). Neither FFP nor determinate survival rates were significantly influenced by B symptoms, unfavorable mediastinal disease, histologic subtype, extent of abdominal disease, the omission of pelvic XRT, the use of whole-lung XRT, or the number of splenic nodules. Patients 40 years of age or older had a 73% determinate survival rate at 10 years compared with 88% for patients younger than 40 years (P = .01). This survival difference was due to treatment-related toxicity in the older group. This study indicates that two cycles of MOPP and XRT to the mantle and upper abdomen is as effective as more intensive treatment for all patients with stage III1 Hodgkin's disease. This treatment program can preserve fertility and has had only a 1% actuarial incidence of ANLL at 15 years.     

Neoadjuvant chemotherapy and radiation therapy compared with radiation therapy alone in advanced nasopharyngeal carcinoma

PURPOSE: To analyze the impact of neoadjuvant chemotherapy on the treatment of locoregionally advanced nasopharyngeal carcinoma and to assess the outcomes of patients receiving such treatment. METHODS AND MATERIALS: We analyzed 137 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with either radiation therapy only or combined radiation therapy and chemotherapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC Stage III-21, Stage IV-61 in the radiation therapy group (RT group); AJCC Stage III-1, Stage IV-54 in neoadjuvant chemotherapy and radiation therapy group (CT/RT group). The median follow-up for surviving patients was 48 months. RESULTS: The 5-year overall survival (OS) rates were 71% for the CT/RT group and 59% for the RT group (p = 0.04). The 5-year actuarial disease-free survival (DFS) rates were 63% for the CT/RT group and 52% for the RT group (p = 0.04). Distant metastasis (DM) incidence was significantly lower in the CT/RT group. The 5-year freedom from distant metastasis rates were 84% for the CT/RT group and 66% for the RT group (p = 0.01). The incidence of locoregional failures was also lower in the CT/RT group, although this difference did not reach statistical significance (69% vs. 56%, p = 0.09) CONCLUSION: While not providing conclusive evidence, historical evidence from this institution suggests that neoadjuvant chemotherapy significantly improves both overall and the disease-free survival of patients with advanced stage nasopharyngeal carcinoma.     

Stage III Hodgkin's disease--long-term results following chemotherapy, radiotherapy and combined modality therapy

215 patients with stage III Hodgkin's disease (HD) were treated at the Royal Marsden Hospital between 1963 and 1985 (median follow-up 9 years). The actuarial 5- and 10-year survival was 77 and 65%, respectively with 55 and 48% 5 and 10 year disease-free survival. Of 13 variables tested, age was the only independent prognostic indicator for survival on multivariate analysis. Patients aged under 40, 40-59 and over 60 years had a 10-year survival of 76, 41 and 8%, respectively (p much less than 0.001). Ninety-one patients were initially treated with combined chemotherapy and radiotherapy (combined modality therapy, CMT), 73 patients with radiotherapy (RT) and 51 patients with chemotherapy (CT) alone. Patients under 40 years treated with CMT achieved the best disease-free survival (10 year disease-free survival: CMT 68%; RT 38%; CT 45%). The observed survival advantage for CMT was not statistically significant. In patients aged greater than 40 there was no survival or disease-free survival advantage following CMT. Analysis of recurrence pattern confirmed that CMT improves initial disease control both at previously involved and uninvolved sites. Recurrences at previously uninvolved sites continued up to 6 years following CT, up to 8 years following CMT and up to 14 years after RT alone. These results indicate that only long-term follow-up gives the true picture of stage III HD.     

Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin's disease: eight-year update of an Italian prospective randomized study.

PURPOSE: To compare the effectiveness of chemotherapy (CHT) with extended-field radiotherapy (RT) in the treatment of early-stage Hodgkin's disease (ESHD), we report an 8-year updated analysis of a study in which treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) CHT was randomly compared with extended-field RT. PATIENTS AND METHODS: From August 1979 to December 1982, 89 adult patients with pathologic stage I-IIA Hodgkin's disease (HD) were randomly allocated to receive either RT with mantle field followed by periaortic irradiation (n = 45) or six monthly courses of MOPP CHT (n = 44). RESULTS: All patients in the RT arm and 40 of 44 in the CHT arm achieved complete remission. Twelve relapses occurred in each group. Eight patients treated with MOPP and two of the RT arm died of HD. Three other patients of the CHT group died because of a second cancer. With a median follow-up greater than 8 years, the overall survival rate is significantly higher in the RT than in the CHT group (93% v 56%; P less than .001), whereas the rates of freedom from progression and relapse-free survival (RFS) were similar in the two groups (76% v 64% and 70% v 71%, respectively). Of the 12 patients relapsing after RT, 11 (92%) achieved a second CR, compared with only six of the 12 (50%) in the MOPP group. Analysis of the response rate to salvage treatments showed that the type of relapse in the MOPP group was a prognostic indicator for the achievement of a second CR, whereas in the RT group, a second CR was obtained regardless of the characteristics of the relapses. At 80 months, the probability of survival of relapsing patients calculated from time of relapse was 85% and 15% in the RT and CHT groups, respectively (P = .02). CONCLUSION: We conclude that RT alone is the treatment of choice for adult patients with ESHD with favorable prognostic factors.     

Treatment of early stage Hodgkin's disease with radiation therapy plus short-cycle (3 MOPP) adjuvant chemotherapy

Eighty-four consecutive, previously untreated patients with stage I, II A-B and IIIA Hodgkin's disease were treated with combined modality therapy including subtotal or total nodal irradiation, followed by three cycles of MOPP. MOPP was administered before radiotherapy in patients with systemic symptoms or with bulky disease. Seventy-six of 84 patients (90.5%) achieved complete remission, and 8 died from disease progression after a variable period of incomplete remission. Three of 76 (3.9%) relapsed, and 2 of them have been subsequently salvaged. Up to the present time, 70 patients are alive, without evidence of disease; 9 have died from Hodgkin's disease, 2 from acute non-lymphoblastic leukemia, and 3 from intercurrent causes. No death occurred from acute toxicity due to chemotherapy. Actuarial overall survival is 82.3% and freedom from relapse is 81.8% after 48 months' median observation (range: 12-111 months). No significant difference in survival and freedom from relapse has been observed with respect to age, sex, stage, presence or absence of unfavorable prognostic factors. The role of adjuvant chemotherapy and its use in a reduced number of cycles in early stage Hodgkin's disease are discussed.     

Stage IA-IIB Hodgkin's disease: staging and treatment of patients with large mediastinal adenopathy

Ninety-two patients with clinically staged (CS) IA-IIB Hodgkin's disease (HD) with large mediastinal adenopathy (LMA) underwent three different staging and treatment approaches between April 1969 and December 1984. These approaches included: (1) staging laparotomy followed by radiation therapy (RT) alone; (2) staging laparotomy followed by combined RT and chemotherapy (CMT); or (3) clinical staging followed by CMT. Patients treated with CMT were more likely to have "B" symptoms, extension into extranodal sites, or stage III disease. Patients treated with RT alone had a significantly higher risk of relapse as compared to patients receiving CMT. No overall survival differences were seen between the three groups of patients. For patients treated with CMT without RT to the spleen or abdominal nodes, the risk of relapse in the abdomen was low (4%). These data suggest that for those CS I-II HD patients with LMA who are treated with CMT, the role for staging laparotomy and abdominal irradiation is limited. RT alone remains an option for some patients with LMA, but careful assessment of the anatomic extent of thoracic disease as well as staging laparotomy is essential if such treatment is recommended.     

Combined modality therapy for mediastinal Hodgkin's disease. Prognostic significance of constitutional symptoms and size of disease

Combined modality therapy was used in an attempt to increase the complete remission rate and survival of previously untreated patients with Hodgkin's disease. MOPP (nitrogen mustard, vincristine, procabazine, prednisone) chemotherapy was followed by radiotherapy. The median duration of follow-up exceeded 5 years. Complete remissions were achieved in 63 of 71 patients (89%) with mediastinal masses. The actuarial survival of 10 years was 72% for patients with small mediastinal masses (mediastinal mass ratio less than 0.35) and 46% for patients with large mediastinal masses (P less than 0.05). The corresponding disease-free survival figures were 69% and 46%, respectively (P less than 0.05). A small mediastinal mass did not affect prognosis. Systemic symptoms especially affected the prognosis in patients with a large mediastinal mass, since in symptomatic patients the actuarial survival and freedom from relapse were 19%, whereas all asymptomatic patients survived without relapse. In patients with a small mediastinal mass, systemic symptoms had no significant effect on the actuarial survival or disease free survival. Age and stage did not affect the prognosis in patients with large mediastinal masses. It was concluded that MOPP chemotherapy followed by radiotherapy was an adequate treatment for asymptomatic patients with large mediastinal disease. However, in symptomatic patients with large mediastinal masses, this treatment was clearly inadequate.     

Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's disease: the experience of the French Society of Pediatric Oncology.

PURPOSE: With the aim of decreasing undesirable side effects of therapy, we investigated the reduction of both chemotherapy and radiation therapy (RT) in children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy) after good response to chemotherapy. PATIENTS AND METHODS: A French national study began in 1982 that included 238 pediatric patients with Hodgkin's disease. Initial staging was clinical and without laparotomy. In patients with localized disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP. Patients with more advanced disease (IB-IIB-III-IV) received three courses of MOPP that was alternated with three courses of ABVD. All of the patients who achieved a good remission after chemotherapy were administered 20 Gy RT, which was limited to the initially involved areas for localized disease, and encompassed the paraaortic nodes and the spleen as well for more advanced stages. When a good remission was not obtained, 40 Gy RT was administered. RESULTS: At the completion of chemotherapy, 227 patients (97%) were considered good responders, whereas 11 did not achieve a good remission. With a median follow-up of 6 years, the 6-year actuarial survival was 92% and the disease-free survival was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV patients was discontinued because of poor results. CONCLUSIONS: Present findings indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid therapeutic approach in the vast majority of children with Hodgkin's disease.