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.     

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.     

Is pelvic irradiation necessary in stage III1A Hodgkin's disease?

Eighteen patients with pathologic Stage (PS) III1A Hodgkin's disease were treated with mantle and para-aortic field radiation therapy alone between 1973 and 1988. The median follow-up time is 84 months (range 20-174 months). The 5-year survival and relapse-free survival rates are 76 and 82%. Six patients had extensive splenic involvement or bulky mediastinal adenopathy, and three have relapsed and are dead of disease. Of the other 12 patients, only one has had recurrence of disease and died. Patients with PS III1A Hodgkin's disease are good candidates for mantle and para-aortic radiation therapy only, provided that they do not have extensive splenic involvement or large mediastinal adenopathy.     

Clinical evaluation of combined treatment of stage III(B) Hodgkin's disease

Patients with stage III Hodgkin's disease (110) received 2-3 courses of combination chemotherapy followed by total or subtotal irradiation, or exposure of primarily involved lymph nodes. The study did not include patients with persistent symptoms of intoxication. Overall 5- and 10-year survival rates were 78 and 68%, recurrence-free--75 and 74% respectively.     

Treatment of advanced stage Hodgkin's disease

Hodgkin's disease remains one of the few malignant diseases which can be cured by modern chemotherapy in most cases even in advanced stages. Adriamycin-containing chemotherapy regimens are considered as the standard therapy which induce long-term remission in about 60-70% of patients. The ABVD scheme, developed by Bonadonna and colleagues in Milan, has a favorable toxicity profile and causes less myelotoxicity, acute leukemia or sterility relative to many previous treatment programs containing alkylating agents. However, 20- 30 % of patients eventually relapse and are then frequently treated with high-dose programs including stem cell transplantation. There are two major goals in advanced Hodgkin's disease: (1) to improve the cure rate and (2) to reduce acute and long-term toxicities. The recent definition of prognostic factors identified patients who are at a high risk of treatment failure as well as those in whom less toxic approaches can be applied. The optimal approach or program has not yet been defined, although new chemotherapy regimens such as BEACOPP and Stanford V with increased tumor response rates have been identified. These new drug combinations are currently analyzed and compared with ABVD in several international trials. While the addition of radiotherapy improved disease control in some trials a survival benefit was not identified and the role of radiotherapy remains controversial. High dose programs remain experimental in advanced stage Hodgkin's disease and should be restricted to prospective clinical trials.     

Suprahyoid Hodgkin's disease stage IA.

From 1973 to 1987, 71 patients (age greater than or equal to 16 years) with stage IA supradiaphragmatic Hodgkin's disease were treated with radiotherapy alone. 23 patients (20, clinical stage; 3, pathological stage) had disease localised to the suprahyoid region of the neck (upper deep cervical, 11; submandibular, 6; submandibular and upper deep cervical, 5; submental, 1). The age range was 17 to 64 (median 33). The male to female ratio was 2.8:1. The histological types were: lymphocyte predominant, 11; nodular sclerosis grade I, 8; mixed cellularity, 4. The 5 and 10 year cause-specific survival was 100% with a disease-free survival of 90% at 5 and 10 years. The proportion of patients with suprahyoid Hodgkin's disease IA was constant over the 15-year period. This only became apparent when the histology of patients with suprahyoid non-Hodgkin's lymphoma stage IA was reviewed.     

Radiotherapy of patients with stage III Hodgkin's disease using the method of continuous fractionated irradiation

Clinical rationale for alternating split-course radiotherapy for stage III Hodgkin's disease is discussed. The procedure was employed in 54 such patients. It proved useful in total nodal irradiation for advanced disease, resulting in improved survival. The technique involves a shorter duration of treatment than that of the standard one.     

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.     

Hilar irradiation in early stage Hodgkin's disease

We conclude that inclusion of the hilar region adds little morbidity, while failure to treat is associated with a finite risk of hilar recurrence. It therefore would seem advisable to include the lung roots in "mantle" field techniques in patients with good pulmonary reserve. Our experience with this group of patients, and with others not included here, suggests that the risk of hilar involvement may be particularly pronounced in patients who present with intradiaphragmatic disease. On the other hand, the relapse rate in the hila is sufficiently small that straight-edged mediastinal fields can be used with relative safety in patients with emphysema or other pre-existing dysfunction for whom inclusion of the additional volume might lead to pulmonary insufficiency.     

Management of stage I and II Hodgkin's disease

Early stage Hodgkin's disease is highly curable with radiation therapy alone. Some prognostic factors are associated with increased risk of relapse and may require combined modality treatment. The evolution of treatment of stage I and II Hodgkin's disease is presented.     

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.     

Anatomical substages of stage III Hodgkin's disease: implications for staging, therapy, and experimental design

Twenty-three patients with pathologic stage III Hodgkin's disease were classified with respect to the presence or absence of symptoms (III-A, III-B), the presence or absence of splenic involvement (IIIS+, IIIS-) and anatomic substage--the extent of disease within the abdomen (III1, III2). Stage III1 disease included disease limited to the upper abdomen, i.e., spleen, splenic node, celiac node, and/or portal node. All other more extensive disease was classified as stage III2. Symptoms and splenic involvement did not predict either disease-free survival or survival. However, 5 year actuarial disease-free survival was significantly better in III1 patients as compared to III2 patients (77% vs. 13%, p less than .001). Eight of nine stage III2 patients receiving total nodal radiotherapy alone relapsed. When considered along the previous studies of anatomic substage, these findings suggest that patients in stage III1 and III2 should receive different therapeutic approaches. Analysis of therapeutic results in stage III patients must consider anatomic substage.     

Results of treatment of stage 3A Hodgkin's disease

From 1975 to 1981, 38 patients with Stage 3A Hodgkin's disease (35 patients pathologically staged) underwent mantle and para-aortic irradiation, and in 36 patients this was preceded or followed by at least six cycles of multiagent chemotherapy. Both the 5-year actuarial survival and disease-free survival for all 38 patients were 83%. There have been six treatment failures: two patients have relapsed within irradiated nodal groups, one patient in apical pericardial lymph nodes as a marginal recurrence, one patient concurrently infield and in unirradiated nodal groups, and two patients systemically (concurrently in unirradiated nodal groups). Of these six relapses, three patients have died of Hodgkin's disease, one patient has been salvaged, and two patients currently are under treatment for salvage. One patient has developed acute nonlymphocytic leukemia and died of this disease. Extensive disease, as estimated by the number of sites of involvement at presentation, degree of splenic involvement, extent of intra-abdominal disease or mediastinal involvement, did not reveal statistically significant prognostic subgroups for relapse. It is currently recommended that patients with Stage 3A Hodgkin's disease receive six cycles of multiagent chemotherapy and mantle and para-aortic irradiation.     

Inaugural intra-atrial neoplastic thrombosis in stage II Hodgkin's disease

We report the first case of intra-atrial neoplastic thrombosis discovered in the initial stage of Hodgkin's disease. Considering the course of the case and the recurrence after 18 months we emphasize the necessity of screening cardiac cavities by CT Scan with a bolus, and of treating such a case as an initial stage IV Hodgkin's disease.     

Results of treatment of stage IA and IIA Hodgkin's disease

This study analyzed the 5 year actuarial survival and disease-free survival of 122 patients with Stage IA and IIA Hodgkin's disease, (108 patients laparotomy staged) treated with mantle and paraaortic irradiation from 1975 to 1981. Prognostic subgroups and patterns of treatment failure were investigated. The 5 year actuarial survival and disease-free survival was 91% and 75% respectively for the entire group. For Stage IA patients, the 5 year survival and disease-free survival was 92% and 86% respectively, whereas for those in Stage IIA the respective figures were 86% and 65%. Individuals with greater than four sites of involvement at initial presentation; extensive mediastinal adenopathy; hilar or extramediastinal extension to lung, pleura or pericardium, had a poorer 5 year actuarial disease-free survival (43%-60%) than those without these factors (70%-85%). Of the 122 patients, there were 26 relapses: nine infield failures; two concurrent infield and systemic failures; nine marginal recurrences, and three relapses occurring systemically and three in nodal groups not irradiated. Following relapse, 17 patients were salvaged with chemotherapy. Two patients are alive with disease and seven patients died of Hodgkin's disease. Patients with less extensive mediastinal adenopathy and supradiaphragmatic nonmediastinal presentations can be satisfactorily treated with mantle and paraaortic irradiation, whereas patients with extensive mediastinal adenopathy receive six cycles of multiagent chemotherapy before irradiation.