Hodgkin's disease in children: treatment with low dose radiation and MOPP without staging laparotomy: a preliminary report.

Twenty-seven children with previously untreated Hodgkin's disease (CS I-2, II-13, III-3, IV-9) were given three cycles of MOPP to induce a remission which was consolidated with extended field radiation (2000--3500 rad) and three cycles of MOPP. Surgical staging was discontinued. Twenty-five of 27 children have not relapsed (range 15+--64+ months; median 39+ months); two children have died, one of uncontrolled Hodgkin's disease and one of acute infection while in complete remission. Actuarial 3 and 5 year survival rates and relapse-free rates are 91%. The merits of this treatment approach are discussed.     

Postchemotherapy staging laparotomy in Hodgkin's disease.

Seventeen patients with Hodgkin''s disease who had a staging laparotomy (SL) within 2 months of the completion of initial chemotherapy are presented. Only 1 patient had a positive laparotomy. Postchemotherapy SL allows any residual active disease to be assessed, but the incidence of positive finding may be small, and such findings are unlikely to alter subsequent management. SL following chemotherapy is therefore not recommended either for patients in clinical remission or for patients with evidence of relapsed disease.     

Costs and effectiveness of staging and treatment options in early-stage Hodgkin's disease.

PURPOSE: Using a cost-effectiveness analysis, to weigh the costs and benefits of the different staging and treatment options in early-stage Hodgkin's disease. METHODS: We constructed a decision-analytic model for a hypothetical cohort of 25-year-old patients with early-stage Hodgkin's disease. Markov models were used to simulate the lifetime costs and prognosis of each staging and treatment strategy. Baseline probabilities and cost estimates were derived from published studies and bills of relevant patient cohorts. RESULTS: Among the six management strategies considered, the incremental cost-effectiveness ratio of laparotomy and tailored treatment compared with mantle and para-aortic-splenic radiation therapy in all clinical stage I-II patients was $24,100/quality-adjusted life year, while that of the strategy of combined modality therapy in all clinical stage I-II patients compared with laparotomy was $61,700/quality-adjusted life year. All the remaining strategies were dominated by one of these three strategies. Sensitivity analysis showed that the cost-effectiveness ratios were driven predominantly by the effectiveness rather than the cost of each strategy. In particular, the analysis was heavily influenced by the utility of the post-laparotomy health state. CONCLUSIONS: In considering the various alternative management strategies in early-stage Hodgkin's disease, even very small gains in effectiveness were enough to justify the additional costs of more expensive treatment options.     

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.     

The staging of Hodgkin's disease

The approach to staging patients with Hodgkin's disease has changed over the last 20 years. Although careful physical examination, chest radiograph, and bipedal lymph-angiogram remain the mainstays of the clinical evaluation, computed tomography (CT) scanning of the chest and abdomen is rapidly gaining acceptance as a useful ancillary procedure. In addition, the initial enthusiasm for the staging laparotomy and splenectomy as a necessary part of the staging evaluation is now coming into question. Recent studies raise legitimate concerns about this procedure's overall impact upon survival as well as the potential long-term consequences of splenectomy. Select situations do exist, however, where a staging laparotomy remains appropriate. An approach to the staging of newly diagnosed Hodgkin's disease is suggested and supported by recent studies of this disease.     

Long-term results of polychemotherapy for Hodgkin's disease in children

In 1974-2000, 49 patients (up to 15 years), with Hodgkin's disease at different stages, for different reasons, received polychemotherapy alone. Overall 5-year survival was 72.4%; 10 years-64.5%, and 15 years--52.7%. A correlation was established between survival, on the one hand, and stage and general symptoms, on the other: stages--I-IIIA--76.8%; IIIB-IVAB--37.7%; polychemotherapy--6 cycles--67.9%; more than 6 cycles--100%; age up to 10 years--75.8%; more than 10 years--45%.     

Subdiaphragmatic Hodgkin's disease: laparotomy and treatment results in 49 patients

The clinical records of 1,616 patients with previously untreated Hodgkin's disease were reviewed. Forty-nine of these patients (3%) presented with disease limited to sites below the diaphragm and underwent laparotomy as part of their staging evaluation. The clinical and histological characteristics of this group of patients with subdiaphragmatic Hodgkin's disease are compared with those who presented with supradiaphragmatic disease. Splenectomy in 47 patients revealed splenic involvement in 16 (39%), and bulky splenic involvement (more than five gross nodules) in ten (24%). The final pathological stage (PS) distribution was PS I = 8, PS II = 37, PS IV = 4. No clinical stage (CS) IA patients and only two of 20 patients with negative paraaortic nodes on lymphogram had splenic involvement in contrast to eight of nine CS IIB patients. Freedom from relapse and survival were similar to patients with equivalent stage supradiaphragmatic disease. Splenic involvement and bulky splenic involvement were associated with a significantly decreased survival. Twelve out of 44 PS IA to IIB patients relapsed. In eight of these 12 patients, relapse was limited to sites above the diaphragm and another two patients relapsed both above and below the diaphragm. Patients who received total lymphoid irradiation were less likely to relapse above the diaphragm than patients who received no supradiaphragmatic irradiation. We recommend that CS IA and IIA patients with subdiaphragmatic disease undergo staging laparotomy and receive supradiaphragmatic irradiation as part of their treatment. Laparotomy may not be necessary for CS IIB patients who are at high risk for splenic disease if chemotherapy is planned as part of their treatment program.     

Lymphocyte predominant Hodgkin's disease: clinical presentation and results of treatment

The records of 59 patients with lymphocyte predominant Hodgkin's disease (LPHD) evaluated and treated at Stanford University Medical Center between 1963 and 1983 were reviewed. Of these 59 patients, 92% are alive at 10 years following treatment, 78% are relapse-free, and none have died of Hodgkin's disease. Compared with the other histologic subtypes of Hodgkin's disease, LPHD presents more frequently as stage I or II disease (78% vs. 55%) and less frequently with constitutional symptoms (7% vs. 32%). Despite these factors, there is no statistically significant difference in either survival or freedom-from-relapse (FFR) between the histologic subtypes when comparisons are made on a stage-for-stage basis. Analysis of sites of presentation and relapse reveals that LPHD rarely involves intrathoracic structures. Patients with C.S. I disease presenting in inguinofemoral or high cervical lymph nodes do not require staging laparotomy as none of these patients were upstaged by surgery. Patients with stage I disease involving high cervical lymph nodes may be treated with limited field irradiation employing fields no more extensive than a mantle and Waldeyer's ring field, as no relapses have been seen in such patients treated in this fashion. Although limited field irradiation was used successfully for LPHD presenting in other localized sites, inadequate patient numbers preclude assessment of this treatment for those clinical presentations.     

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.     

Liver and spleen scintigraphy in staging Hodgkin's disease

Liver–spleen scintigraphy is a useful adjunctive procedure in the diagnosis and staging of Hodgkin's disease. Scintigraphy is easily obtained for both the patient and the physician. It usually directs attention to a liver or spleen involved with the disease by revealing organomegaly with or without defects in concentration of radioactive colloid. The information may be diagnostic. Patients are presented who were studied with lymphangiography, diagnostic laparotomy with splenectomy, and liver–spleen scintigraphy among other tests for staging. The routine use of liver–spleen scintigraphy is recommended in the diagnosis and management of Hodgkin's disease.     

Involved field radiation therapy for early stage Hodgkin's disease in children: preliminary results.

Twenty Stage I and II children with Hodgkin's disease were treated with involved field radiation therapy. Twelve patients were Stage I. The histologic types were:nodular sclerosis(seven cases), mixed cellularity (two) and lymphocyte predominant (three). There were eight Stage II patients (six nodular sclerosis and two of mixed cellularity). One Stage I and 4 Stage II patients had class B disease. Involved field irradiation was used in these children after staging laparotomy showed no disease below the diaphragm. Eight of the 20 patients relapsed, five in lymph nodes adjacent to the primary site, two in areas across the diaphragm; the other had both local and distant extension. The median time to relapse after completion of radiation therapy for Stage I and II were 15 and 5 months, respectively. Two of the eight children with recurrent disease are dead. The other six were retreated and are alive and free of disease for periods ranging from 24 to 68 months after original treatment (median, 36 months). Two of the six survivors in this group received irradiation to the site of the recurrent disease only, one was given total nodal irradiation, and three had chemotherapy. The other 12 patients are in continuous first remission. They have been followed for a median time of 26 months. The actuarial relapse-free survival and survival rates at 3 years are 57 and 89%, respectively.