The management of metastatic seminoma testis

Clinical details of 85 men presenting with previously untreated metastatic seminoma are presented. In Stage II disease relapse rate was related to the size of metastases. In IIA (32 patients) the relapse rate was 9.4%; IIB (11 patients), 18.2%; and IIC (23 patients), 39.1%. The continuous disease-free survival rate was significantly worse for IIC than IIA and IIB patients (P = 0.023). No instance of first relapse in supradiaphragmatic nodes was observed in 13 men with Stage II disease treated with irradiation limited to infradiaphragmatic nodes. In relapsing Stage IIC patients, extralymphatic metastasis was as frequent as abdominal relapse. On the basis of these observations, together with preliminary data in nine men receiving Cis-platinum-containing chemotherapy, all of whom are in complete remission, it is proposed that patients with Stage IIA and IIB disease should receive infradiaphragmatic irradiation with chemotherapy deferred until relapse. Stage IIC patients should receive chemotherapy initially, followed by irradiation. In Stage III and IV disease chemotherapy should be initial therapy with radiotherapy for bulky disease on an individualised basis. Moderate elevation of blood B-HCG levels is not inconsistent with a diagnosis of pure seminoma and does not appear to influence adversely the outcome of radiotherapy.     

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.     

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.     

A randomized study comparing chemotherapy alone with chemotherapy followed by radiotherapy in patients with pathologically staged IIIA Hodgkin's disease

This paper reports the five-year follow-up (range, 1-8 years) of 56 patients with pathologic stage IIIA Hodgkin's disease randomized for chemotherapy alone or chemotherapy followed by radiotherapy to previous areas of disease (26 treated with mustine, vinblastine, procarbazine, and prednisolone [MVPP] alone, 30 with MVPP and radiotherapy). Of the 56 patients 53 (95%) achieved a complete remission with chemotherapy and of these only five (9%) have relapsed; three died of Hodgkin's disease. There was no improvement in relapse-free survival associated with the uses of radiotherapy following chemotherapy but in view of the small numbers of relapses and the excellent results following chemotherapy alone, a significant improvement could not be expected. The use of MVPP alone can be recommended as an alternative therapy for patients with stage IIIA Hodgkin's disease. This avoids both the physical and psychologic morbidity associated with the high relapse rate following extensive primary radiotherapy and the necessity of combined modality treatment for about half these patients. The question of whether radiotherapy should be given to areas of previous bulk following chemotherapy has not yet been answered in this trial which is continuing.     

Stage IIB Hodgkin's disease: the Stanford experience

Between 1968 and 1982, 126 patients with pathologic stage (PS) IIB Hodgkin's disease were treated at Stanford University with either irradiation alone or irradiation combined with chemotherapy. Actuarial survival and freedom from relapse rates at 10 years for the overall group were 81% and 74% respectively, with no statistically significant difference between the treatment approaches. The impact of the severity and number of constitutional (B) symptoms, as defined by the Ann Arbor Conference, was analyzed. Patients who presented with all three B symptoms had significantly poorer survival and freedom from relapse compared with those patients with only one or two B symptoms (for survival differences, P = .005 and .007; for freedom from relapse differences, P = .002 and .04). Male sex was the only other prognostic factor that correlated with a poor outcome. At 10 years, the survival rate was 66% for males v 84% for females (P = .01), and the freedom from relapse rate was 75% for males v 89% for females (P = .02). The presence of extralymphatic sites of involvement, age greater than 40, or involvement of greater than three lymphoid sites had no significant adverse effect on either freedom from relapse or survival. Patients with large mediastinal masses treated with irradiation alone had a 10-year freedom from relapse rate of 54% v 81% for those treated with combined-modality therapy (P = .15), but there was no significant difference in survival rates (85% for irradiation alone v 71% for combined modality therapy). Treatment recommendations for stage IIB Hodgkin's disease are discussed.     

Management of stage II Hodgkin's disease: 15 years experience at St. Bartholomew's Hospital.

One hundred seventy-seven consecutive patients with newly diagnosed stage II Hodgkin's disease (HD) (supradragmatic 157; infra diaphragmatic 20) were treated at St. Bartholomew's Hospital on the basis of pathologic stage (PS) in 84 (IIA 69; IIB 15) and clinical stage (CS) in 93 (IIA 33, IIB 60) between January 1968 and December 1984. The median follow up is 13 years. Overall, complete remission (CR) was achieved in 143 patients (75%) of whom 53 have had a recurrence. One hundred twenty-seven patients remain alive, the cumulative predicted survival at 15 yrs being 70%. Mantle radiotherapy was prescribed to 88 patients with supradiaphragmatic HD, of whom 75 entered CR and 9 achieved good partial remission (GPR) (95%). The duration of remission correlated strongly with ESR (greater than 50 mm/h) and mediastinal thoracic ratio (less than 33% vs. greater than 33%) in a multivariate analysis (p = 0.05 and 0.02, respectively). 46/88 patients remain in continuous first remission, the median duration of remission having not reached at 15 years. Combined modality therapy or chemotherapy alone was prescribed to 69 patients with supradiaphragmatic HD, CR being achieved in 51 patients and GPR in 8 at the completion of all therapy. 48/59 patients continue in first remission. The duration of remission of patients receiving combined modality therapy or CT alone was significantly longer (p = 0.002) than that of patients receiving RT alone, in spite of the fact that the former group comprised predominantly of patients with unfavourable features.(ABSTRACT TRUNCATED AT 250 WORDS)     

Therapy studies of the German Hodgkin's Study Group. Intermediate results of the study protocols HD1, HD2, and HD3

Between July 1983 and September 1986 358 untreated patients with Hodgkin's lymphoma qualified for the protocols HD1 (stages I to IIIA with risk factors), HD2 (stage IIIA), and HD3 (stages IIIB and IVAB). Patients in HD1 received a combined chemo-radiotherapy (2 X COPP/ABVD + 40 Gy EF vs. 2 X COPP/ABVD + 20 Gy EF). Patients in HD2 were randomized into radiotherapy (TNI 40 Gy) vs. combined chemo-radiotherapy (2 X COPP/ABVD + 20 Gy IF). Patients in HD3 received induction chemotherapy (3 X COPP/ABVD) and were randomized into consolidation by radiotherapy (20 Gy IF) vs. chemotherapy (1 X COPP/ABVD). In HD1, 51 out of 65 evaluable patients (78%) achieved a complete remission. The survival of HD1 patients is as good as the survival of patients in stages I and II without risk factors. In HD3, 58 out of 93 patients (62%) achieved complete remission after induction chemotherapy with COPP/ABVD. This is significantly better than the 31% complete remission rate observed in a pilot study with COPP alone (p less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 X CEVD in case of persisting disseminated disease), a total of 71% complete remissions in stages IIIB/IVAB were achieved. The progression-free survival of HD3 patients who received consolidation therapy is significantly longer than of patients who refused consolidation therapy.     

Stage III Hodgkin's disease: improved survival with combined modality therapy as compared with radiation therapy alone

This is a retrospective analysis of 120 patients with pathologically stage IIIA and IIIB Hodgkin's disease treated from April 1969 to December 1982. The median follow-up was 108 months. Treatment consisted of radiation therapy (RT) alone in 54 patients and combined radiation therapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy (CMT) in 66 patients. Stage III patients treated with CMT have an improved actuarial 12-year survival as compared with patients treated with RT alone with MOPP reserved for relapse (80% v 64%; P = .026). The 12-year actuarial freedom from first relapse by treatment for stage III patients is 83% and 40%, respectively (P less than .0001). Improved survivals following combined modality therapy are seen for the following subgroups of stage III patients: stage III2, 66% (CMT) v 44% (total nodal irradiation; TNI), P = .04; stage III1, 97% (CMT) v 73% (TNI), P = .05; stage III mixed cellularity or lymphocyte depletion histology, 94% (CMT) v 65% (TNI), P = .007; and stage III extensive splenic involvement, 77% (CMT) v 58% (TNI), P = .02. These survival differences are not seen in patients with nodular sclerosis or lymphocyte predominance histology or in patients with minimal splenic involvement. These data indicate that the initial use of CMT in stage III Hodgkin's disease results in an improved survival as compared with initial treatment with RT with MOPP reserved for relapse. Patients with limited Stage IIIA disease may still be candidates for radiation therapy alone.     

Treatment of pediatric Hodgkin's disease with chemotherapy alone or combined modality therapy

Optimal treatment for Hodgkin's disease during childhood is unknown. We report the treatment outcome of patients with Hodgkin's disease <13 years of age seen at the American University of Beirut Medical Center (AUBMC) between 1980 and 1996. A retrospective review of the medical records of 24 children treated for HD at AUBMC was performed. Treatment consisted of chemotherapy alone (n = 15) or chemotherapy plus involved field radiotherapy (n = 9). Chemotherapy consisted of COPP, ABVD, or alternating cycles of each for a total of 6 to 12 cycles, depending on clinical and radiological response; three patients received MOPP. Five patients in the chemotherapy group had clinical stage (CS) I and II and 10 had CS III disease. In the combined modality group, eight patients had CS I and II and one had CS IV disease. At a median follow-up of 5 years, the event-free survival (EFS) for the combined modality group was 100% and the overall survival (OS) 100%. For the chemotherapy alone group, the EFS was 56% and the OS was 79%. Four patients (27%) in the chemotherapy alone group who had Stage IIIB disease relapsed. Mean time to relapse was 4.3 years. In our experience, six cycles of COPP or (COPP plus ABVD) alone were suboptimal for the treatment of Stage IIIB Hodgkin's disease patients, especially those with involvement of lower abdominal nodes (III2B), extensive pulmonary disease, or mixed cellularity histology. Radiation therapy or additional chemotherapy courses are required for these patients.     

Patterns of survival in patients with Hodgkin's disease: Long follow up in a single centre

BACKGROUND:: Prolonged remission can now be induced in the majority of patientswith Hodgkin's disease with chemotherapy and/or irradiation.However, there is a significant proportion of patients in whomthis approach fails, either at presentation or subsequently.Survival is the definitive endpoint to assess treatment efficacy.In this study, the survival patterns of a large group of consecutivepatients treated in a single institution are presented. RESULTS:: The overall median survival was 18.3 years. Clinical remission(complete remission plus good partial remission) was inducedin 443 (85%); the median survival of patients in remission hasnot been reached. Fifty-eight patients achieved responses lessthan clinical remission with initial therapy (partial response)or had progressive disease, the median survival of this groupbeing 1.4 years. With further therapy, remission was subsequentlyinduced in 10; 5 are still alive, 5 have died between 1.9 yearsand 14.3 years. Twenty patients died before completion of therapy.Recurrence has been documented in 147 of the patients in remission(following initial therapy) over a median follow up period of13 years (minimum 5 years). One hundred forty-three of thesepatients were retreated following recurrence (105 chemotherapy,28 radiotherapy, 6 combined modality treatment and 4 surgery).Second remission was induced in 109/143 (76%). There was a trendtowards better second remission induction in patients whosefirst remission was longer than 1 year (p = 0.06). The medianduration of second remission was inferior to first remissionduration (p < 0.001). There was no correlation between durationof first remission and survival following recurrence (p = 0.8)or with duration of second remission (p = 0.54). There was nosignificant difference in duration of second remission betweenpatients who were initially treated with radiotherapy or chemotherapy(p = 0.3). The median survival following second remission was12.0 years, being the same for patients with initially localizeddisease (stages I and II) treated with radiation alone and forpatients with advanced Hodgkin's disease (stages III and IV)treated with chemotherapy. Survival after recurrence is significantlybetter for patients under 50 years at the time of recurrence(p < 0.001). Second recurrence was documented in 46 patients,third remission being reinduced in 22, the median survival ofthe latter being 5.1 years. CONCLUSION:: These results illustrate the importance of prolonged followup in defining the clinical course of patients with HD and arevital for planning experimental chemotherapy at the time oftreatment failure or recurrence. Hodgkin's disease, salvage therapy, recurrence, relapse, resistant disease, chemotherapy, radiotherapy, survival, remission     

Results of a prospective trial of mantle irradiation alone for selected patients with early-stage Hodgkin's disease.

PURPOSE: To determine the efficacy of mantle radiation therapy alone in selected patients with early-stage Hodgkin's disease. PATIENTS AND METHODS: Between October 1988 and June 2000, 87 selected patients with pathologic stage (PS) IA to IIA or clinical stage (CS) IA Hodgkin's disease were entered onto a single-arm prospective trial of treatment with mantle irradiation alone. Eighty-three of 87 patients had > or = 1 year of follow-up after completion of mantle irradiation and were included for analysis in this study. Thirty-seven patients had PS IA, 40 had PS IIA, and six had CS IA disease. Histologic distribution was as follows: nodular sclerosis (n = 64), lymphocyte predominant (n = 15), mixed cellularity (n = 3), and unclassified (n = 1). Median follow-up time was 61 months. RESULTS: The 5-year actuarial rates of freedom from treatment failure (FFTF) and overall survival were 86% and 100%, respectively. Eleven of 83 patients relapsed at a median time of 27 months. Nine of the 11 relapses contained at least a component below the diaphragm. All 11 patients who developed recurrent disease were alive without evidence of Hodgkin's disease at the time of last follow-up. The 5-year FFTF in the 43 stage I patients was 92% compared with 78% in the 40 stage II patients (P =.04). Significant differences in FFTF were not seen by histology (P =.26) or by European Organization for Research and Treatment of Cancer H-5F eligibility (P =.25). CONCLUSION: Mantle irradiation alone in selected patients with early-stage Hodgkin's disease is associated with disease control rates comparable to those seen with extended field irradiation. The FFTF is especially favorable among stage I patients.     

ChlVPP therapy for Hodgkin's disease: Experience of 960 patients

BACKGROUND: Combination chemotherapy or combined chemo-radiotherapy is thetreatment of choice for patients with advanced stage Hodgkin'sdisease and for patients failing curative radiotherapy. Increasingly,particularly in Europe, patients with early stage disease withpoor prognostic features are also primarily treated with chemotherapyor combined chemo-radiotherapy. We analyzed the experience of4 research groups which used ChlVPP, with or without radiotherapy,as standard chemotherapy for Hodgkin's disease. PATIENTS AND METHODS: Patients with Hodgkin's disease were treated with ChlVPP chemotherapy:days 1–14: chlorambucil: 6 mg/m²/day, procarbazine: 100mg/m²/day, prednisone or prednisolone: 40 mg/day; Days 1, 8:vinblastine: 6 mg/m²/day. The use of radiotherapy varied acrossresearch groups, with many, but not all, patients receivingradiotherapy. RESULTS: A total of 960 patients were treated. 60% were male, 25% wereaged 50+, 59% had nodular sclerosis histology. Failure-freesurvival (time to first ocurrence of progression, relapse afterresponse or death from any cause) at 5 years by stage was: StageI/IIA (231 patients), 75%; I/IIB (152 patients), 62%; IIIA (180patients), 67%; IIIB/IV (397 patients), 51%. Adverse prognosticfactors for all patients included age 50+ and ‘B’symptoms. Patients aged 50+ of all stages did especially poorlyon ChlVPP therapy. The 34 stage IIIB/IV patients with lymphocytedepleted histology also did poorly. CONCLUSION: These results compare favorably with other reported series.ChlVPP is an appropriate alternative to other chemotherapy regimensfor some Hodgkin's disease patients, often with a reduced toxicityprofile. Other chemotherapy may be preferred in patients greaterthan 50 years of age. chemotherapy, ChlVPP, Hodgkin's disease, longterm results     

Radiation therapy in the management of bulky mediastinal Hodgkin's disease

From July 1981 to July 1985, 20 patients with bulky mediastinal Hodgkin's Disease (maximum mediastinal width divided by the maximum intrathoracic diameter for a mediastinal mass ratio (MMR) greater than 0.33 were treated at Stanford University with definitive radiation therapy alone. The majority of these patients were selected to receive radiation therapy because they had the more favorable characteristics of minimal extralymphatic involvement, mediastinal masses that were superior and central in location, and a MMR less than or equal to 0.50. All 20 patients were laparotomy staged, and 17 received some radiation to the mantle before laparotomy. Seventeen patients had pathologic stage (PS) II disease (13 PS IIA, 4 PS IIB), two had PS IIISA, and one had PS IB. Eleven patients (55%) had extralymphatic involvement. All patients were irradiated to the mantle field using a shrinking field technique (mediastinal dose, 4400 to 5500 cGy, mean 4990 cGy). After completion of the mantle, all patients with good clinical responses received infradiaphragmatic radiation. Treatment complications included two cases of mild radiation pneumonitis, five of hypothyroidism, five of localized Herpes zoster, one of amenorrhea, one of non-Hodgkin's lymphoma, and one of sepsis. Four patients relapsed. All had an intrathoracic component to their failure. All four patients were salvaged with MOP(P) chemotherapy and are currently alive and free of disease. For the entire group, the actuarial freedom from relapse is 80% at 7 years and the survival is 100%. Median follow-up time is 67 months. The authors conclude that radiation therapy alone is effective in the management of selected patients with Hodgkin's disease who have extensive mediastinal involvement, even when the MMR exceeds 1/3.     

Prognostic factors for patients relapsing after radiotherapy for early-stage Hodgkin's disease

Prognostic factors were analyzed retrospectively in 109 patients who relapsed after treatment with radiation only for Hodgkin's disease. Factors analyzed included initial stage, age, time to first relapse, histology, sex, extent of initial irradiation, sites of relapse, relapse stage (RS), average relative dose intensity (ARDI) of chemotherapy, and type of salvage therapy. Ninety-three percent of the patients received either standard or modified mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). With a median follow-up of 8.3 years, the actuarial survival and freedom from second relapse (FF2ndR) was 57% at 10 years. The extent of disease at the time of relapse, or so-called RS was found to be the single most important prognostic factor. Nearly 90% of patients with RS IA or IEA (favorable group) were disease free, and nearly 60% of patients with RS IIA, IIEA, or IIIA (intermediate group) were disease free compared with only 34% of patients with B symptoms or stage IV disease (unfavorable group). In a subset analysis, the use of combined modality therapy (CMT) was associated with an improved FF2ndR and survival in patients from the intermediate and unfavorable relapse groups. Age greater than 50 years was associated with an increased risk of second relapse and a lower survival. The other factors analyzed appeared to be of no independent prognostic value.     

Follicular large cell lymphoma: analysis and prognostic factors in 62 patients

Sixty-two patients with follicular large cell lymphoma were treated between 1973 and 1981. The overall median survival was 78 months with a five-year survival of 62%. The complete remission rate was 76%, with a median relapse-free interval of 72 months for responders. Complete remission produced a significantly longer survival than partial response and failure. Patients who tolerated therapy with an intensive doxorubicin-containing regimen had a significantly longer relapse-free interval and survival. Patients with stage I-II disease treated with radiation therapy alone had a higher relapse rate than those treated with radiation and combination chemotherapy. The addition of radiation therapy to combination chemotherapy in stage III-IV disease decreased the incidence of relapse at irradiated sites, but did not translate into improved survival. Pretreatment prognostic factors associated with poor response were thrombocytosis and stage III-IV disease; those associated with shortened survival were thrombocytosis, elevated lactic dehydrogenase level, stage III-IV disease, and bulky abdominal disease. Follicular large cell lymphoma is an aggressive lymphoma. Treatment should be curative in intent, and should include intensive combination chemotherapy even in stage I-II disease. Knowledge of important prognostic factors can be useful for analysis of future trials and planning therapeutic strategies.     

The impact of stage and treatment modality on the likelihood of second malignancies and hematopoietic disorders in Hodgkin's disease

Two hundred patients treated with curative intent for Hodgkin's disease between October 1964 and April 1984 at a single institution were studied retrospectively for development of second malignancies. The minimum follow-up was 2 years (median, 11 years). The staging distribution was IA-B, 61; IIA, 54; IIB, 20; IIIA, 46; and IIIB, 19. Sixty-one percent of the patients had laparotomy. Initial management was irradiation alone (RA) in 143 patients and a combination of chemotherapy and irradiation (CB) in 57 patients. Actuarial 10-year survival rates were 82%, IA-B; 78%, IIA; 66%, IIB; 66%, IIIA; and 24%, IIIB. Cause-specific deaths due to Hodgkin's disease or complications of initial or salvage therapy occurred in 3% of IA-B patients, 18% of IIA-B patients, and 35% of IIIA-B patients. One patient had a prior T3N1 squamous cell carcinoma of the retromolar trigone, and a second was diagnosed with concurrent Hodgkin's disease and granulocytic sarcoma. Subsequent solid tumors have occurred in six patients from 5 to 21 years after treatment, including papillary carcinoma of the thyroid, renal cell carcinoma, unilateral breast carcinoma, cervix carcinoma in situ, and lung carcinoma after RA, and bilateral breast carcinoma after CB. Seven fatal hematopoietic disorders (HPDs) were observed, including four acute leukemias, one dysmyeloproliferative syndrome (DMPS), one autoimmune hemolytic anemia, and one aplastic anemia. Two occurred in patients initially managed with RA who subsequently required chemotherapy for relapse. Five HPDs occurred in patients initially managed with CB who never relapsed. All HPDs were observed between 2 and 7.5 years after administration of chemotherapy. Statistical analysis of the data using a rerandomization test on Gehan ranks of treatment and clinical variables showed significant correlations between development of a secondary HPD and (1) initial management with CB; (2) higher doses of chemotherapy; and (3) more advanced disease, particularly IIIB. When only the five events generally associated with treatment (i.e. the four leukemias and one DMPS) were considered, there was a significant correlation with exposure to chemotherapy and presentation with advanced disease. The patient population was small so that interdependence between treatment factors and initial extent of disease in affecting the risk of a secondary HPD cannot be discounted but should be further investigated with larger patient populations.     

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.     

Laparotomy-staged IA versus IIA Hodgkin's disease. A comparative study with evaluation of prognostic factors for stage IIA disease

Ninety-one laparotomy-staged (LAP) IA and IIA Hodgkin's disease (HD) patients were analyzed to evaluate the prognostic significance of stage, mediastinal status, extranodal disease and histology. Forty IA patients were treated with radiotherapy (XRT) only; of 51 IIA patients, 44 received XRT only and 7 had additional chemotherapy. Disease-free survival (DFS) at 5 and 10 years was 81% and 70%, respectively, with overall survival (S) of 93% and 86%, respectively. Disease-free survival for IA patients (93% at 5 and 10 years) was significantly superior to IIA (73% at 5 years, 52% at 10 years). Survival differences were not statistically significant. For IIA patients receiving XRT only, large mediastinal disease was an adverse factor for DFS. Small mediastinal disease in IIA was significantly better than no mediastinal disease. For the whole group of LAP IA and IIA treated by XRT only, three prognostic groups were identified: (1) Stage IA and Stage IIA with mediastinal disease, but less than 7.5 cm in width was highly favorable with less than 10% relapse; (2) Stage IIA nonmediastinal had an intermediate prognosis with relapse in about 33%; (3) Stage IIA large mediastinal (greater than or equal to 7.5 cm) had an unfavorable DFS with relapse in about 55%. The third group contained a highly unfavorable subset with mediastinal masses greater than 10 cm, all of whom relapsed. Salvage therapy was successful in 60% of relapsing patients. In the context of relatively effective salvage therapy, the role of adjuvant chemotherapy in adverse prognostic groups is discussed and it is concluded that the only clearly justifiable use for adjuvant chemotherapy is in patients with massive (greater than 10 cm) mediastinal adenopathy.     

Two cycles of MOPP and radiotherapy: effective treatment for stage IIIA and IIIB Hodgkin's disease

Two cycles of MOPP (mechlorethamine, vincristine (Oncovin), procarbazine, prednisone) and radiotherapy were used to treat 197 patients with stage III Hodgkin's disease. Prior to 1980, radiotherapy was delivered to the mantle, abdomen and pelvis; thereafter, pelvic irradiation was deleted for patients with stage III1 disease. Complete remission rates for IIIA and IIIB presentations were 91% and 89%. The 10-year freedom from tumor mortality (FTM) rate for all patients was 81%; for IIIA, it was 87% and for IIIB, it was 72%. Results were not significantly affected by gender, age, pathology, or deletion of pelvic radiotherapy. However, a subgroup of 28 patients with a tumor burden that included pelvic disease who also had B symptoms was identified as having a poor prognosis. Their FTM was 43%, compared with 87% for all other patients combined (P = 0.002). Based on this analysis, we conclude that limited chemotherapy in combination with radiation therapy can yield results similar to programs that use more chemotherapy for all patients with IIIA disease and for most patients with stage IIIB. However, patients with tumor burdens which include pelvic disease and B symptoms require a different approach.     

Treatment with MOPP or ChlVPP chemotherapy only for all stages of childhood Hodgkin's disease

Fifty-three children with Hodgkin's disease were clinically staged and treated with chemotherapy alone. Forty-six received mechlorethamine (Mustargen; Merk Sharpe & Dohme, West Point, PA), vincristine (Oncovin; Eli Lilly and Company, Indianapolis), procarbazine, and prednisolone (MOPP) and 7 chlorambucil, vinblastine, prednisolone, and procarbazine (ChlVPP). There were four events in the 38 children with stage I and II disease. One patient with massive mediastinal disease failed to remit and subsequently failed mantle irradiation and changes of chemotherapy. Another relapsed at the site of local disease and was salvaged with involved field irradiation and further courses of MOPP. Two other children died as a result of acute graft-v-host disease (GVHD) following transfusion. At autopsy there was no evidence of Hodgkin's disease. Fifteen children had stage III and IV disease and 14 achieved complete remission (CR) and none have relapsed. The child who failed to achieve remission died of virus infections. A mediastinal mass greater than 1/3 the thoracic width was present in 19 children of whom 18 achieved remission and none relapsed. An infradiaphragmatic presentation occurred in eight, all achieved remission and none relapsed. Overall at a median follow-up time of 45 months survival was 94%; the percent of patients without treatment failure was 92; and the percent without relapse was 98.