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.     

The EORTC treatment of early stages of Hodgkin's disease: the role of radiotherapy

Since 1964, the European Organisation for Research and Treatment of Cancer has conducted three subsequent clinical trials on clinical Stages (CS) I + II Hodgkin's disease (HD) in which 1059 patients have been entered. The first trial compared regional radiotherapy (RT) with mantle field or inverted Y, versus the same RT followed by a weekly injection of vinblastine for 2 years. The relapse free survival (RFS) and overall survival (S) were higher in patients treated by RT and chemotherapy (CT). This benefit, however, was significant only in patients with a mixed cellularity histologic type. The second trial compared the therapeutic efficacy of splenic irradiation versus splenectomy and found that in both arms, RFS and S were identical. Moreover, it was found that splenic involvement was correlated with an increased incidence of relapse in extranodal sites and in non irradiated lymphatic areas. In this trial, CT was given only to patients with poor histologic types, mixed cellularity or lymphocytic depletion. In the third trial, staging laparotomy was performed only to further delineate a good prognostic group which could be treated by RT alone. In this limited treatment group, there was no difference in RFS and S between mantle field and mantle field + para-aortic RT. In the extensive treatment group, total nodal irradiation (TNI) was compared with RT + MOPP. The RFS was slightly lower in the TNI arm, but there was no significant difference in S. The data of the 3 trials underline the importance of prognostic factors in the choice of optimal treatment and show that their significance depends upon the type of treatment. Multivariate statistical analyses showed that the main prognostic factors, which can help to identify the subsets of patients who can be treated by RT alone, are (1) systemic symptoms and elevated erythrocyte sedimentation rate (ESR), (2) the number of involved lymphatic areas, and (3) staging laparotomy. Extended RT (mantle + para-aortic + spleen treatment) gives satisfactory results in patients without systemic symptoms and/or elevated ESR and one or two involved sites, whereas TNI or combined modality treatment becomes mandatory for patients with 3 or more involved sites or splenic involvement and/or systemic symptoms. With proper adjustment of the irradiated volume, a very large proportion of CS I + II patients can be best treated by RT alone.     

The adjuvant role of two cycles of MOPP and low-dose lung irradiation in stage IA through IIB Hodgkin's disease: preliminary results

Fifty-eight laparotomy-staged I and II patients with upper torso presentations of Hodgkin's disease and 8 patients with lymphangiogram-staged lower torso disease were treated with radiotherapy alone or with 2 cycles of MOPP and radiotherapy. Patients with upper torso disease with either no mediastinal or only small mediastinal disease without hilar involvement and with no "B" symptoms were treated with mantle radiotherapy alone. Patients with large mediastinal masses or hilar disease were treated with 2 cycles of MOPP followed by definitive mantle irradiation and low dose lung irradiation. Those for whom "B" symptoms were the only adverse prognostic feature received 2 cycles of MOPP and mantle radiotherapy. Patients with lower torso disease were treated with radiotherapy alone if the disease was limited to the pelvis. Those with more extensive disease received 2 cycles of MOPP prior to radiotherapy. The 4-year survival for all 66 patients was 97%. The corresponding disease-free and freedom from second relapse figures were 77% and 92%. Survival for the patients with unfavorable presentations who received 2 cycles of MOPP and radiotherapy was 100%. It was 92% for the group with favorable presentations who were treated with radiotherapy only.     

Feasibility of different combinations of chemotherapy (6 MOPP) plus radiotherapy in Hodgkin's disease

During a preliminary clinical experience (1973-1977) we experimented three different sequences in associating 6 MOPP cycles (CT) with radiotherapy (RT) for the treatment of stage II and III Hodgkin's disease. A total of 55 consecutive previously untreated patients can be estimated to contribute in defining feasibility, immediate results and toxicity of the combined treatment. In this group of patients RT preceded CT in 20 cases (RT-6 MOPP), the opposite sequence (6 MOPP-RT) was preferred in 16 cases, whilst a split-course CT fitting in the RT (3 MOPP-RT-3 MOPP) was employed in 19 cases. Except for the sequence used with respect to irradiation, the CT was carried out in all the cases according to the classical scheme proposed by De Vita et al. (11). RT was effected with 60Co-teletherapy and a wide field or segmental sequential fields, having variable extension depending on the stage ("extended nodal irradiation" for stage II and III cases with lymph node involvement not below L3; "total nodal irradiation" for the remaining cases in stage III). The programmed doses were 45.0 Gy to the involved areas and 40.0 Gy to the clinically uninvolved regions for the RT-6 MOPP and 6 MOPP-RT groups. Doses of 35.0/30.0 Gy were planned for the 3 MOPP-RT-3 MOPP group. The three different groups are not homogeneous with regard to certain important clinical and pathological characteristics; in fact, a higher quota of stage III patients, with systemic symptoms and spleen positivity is present in the 6 MOPP-RT and 3 MOPP-RT-3 MOPP groups. The combined treatment has achieved a complete clinical remission in 18/20 patients in the RT-6 MOPP group (90.0%), in 12/16 patients of the 6 MOPP-RT group (75.0%), and in 17/19 cases in the 3 MOPP-RT-3 MOPP "sandwich" combination (89.5%). The average overall duration of the treatment was 48 weeks for the sandwich combination, 50 weeks for the RT-6 MOPP group, and 56 weeks for the 6 MOPP-RT association. As regards the sandwich combination, both CT and RT took a reasonable length of time to complete. On the contrary, both the medical treatment and irradiation required an excessively long time and were not well tolerated when preceded by either RT or CT in full doses. In particular, myelosuppression was less acute and prolonged in the 3 MOPP-RT-3 MOPP group, whereas the actual doses of CT and RT were higher than those which can be reached with respect to other groups. Three preliminary cycles of CT considerably reduce the target volumes and complications arising from RT. The first CT time gave an objective response greater than 50% in 9/9 cases of the 3 MOPP-RT-3-MOPP group with mediastinal involvement. In this group, rather considerable pulmonary complications were observed in 3/9 patients (33.3%) with respect to the 40% found for the 6 MOPP-RT group (2/5 cases) and the 67.7% for the RT-6 MOPP group (6/9 cases).     

MOPP chemotherapy plus irradiation for Hodgkin's disease, stages IA to IIIB. Long-term results of the prospective trial H72 (1972-1976, 334 patients)

From April 1972 to December 1976, 334 patients with Hodgkin's disease, CS IA-IIIB, were prospectively treated with combined chemotherapy and radiation. The 166 stages IA and II2A were clinically staged only; the 168 other patients were randomized to clinical or pathological staging. All patients received 3 or 6 cycles of MOPP followed by Mantle field with or without mediastinal irradiation and/or inverted Y or lumbo-aortic field according to initial stage, presentation and protocol. At completion of therapy, 317 patients were in complete remission. Twenty-six patients relapsed and 43 died including 5 with leukemia and 6 with infection. Overall 12-year survival and relapse-free rates are 86.6 +/- 3.08 per cent and 91.5 +/- 3.2 per cent respectively (IA: 95.3 and 95.3 per cent; IIA: 87.8 and 92.1 per cent; IIIA: 83.3 and 100 per cent; IB, IIB: 81.7 and 89.2 per cent; IIIB: 67.8 and 73.7 per cent). The randomized comparison between clinical staging plus 6 cycles of MOPP and laparotomy staging plus 3 cycles of MOPP in final stage II3+A, IB, IIB patients showed no significant 12-year survival differences (90.8 versus 85.6 per cent). With this combined modality treatment policy, high survival rates are obtained using only 3 cycles of MOPP and radiotherapy in CS IA, II2A and in PS II3+, IB, IIB. Laparotomy staging may be unnecessary if 6 cycles of MOPP are employed before irradiation in CS IIA, IB, IIB disease and if 3 cycles of MOPP are followed by irradiation in CSIA and II2A disease. Mediastinal irradiation can be avoided in patients with supradiaphragmatic disease without mediastinal involvement.     

Impact of adjuvant radiation on the patterns and rate of relapse in advanced-stage Hodgkin's disease treated with alternating chemotherapy combinations

The role of adjuvant radiation therapy (RT) in the management of advanced-stage Hodgkin's disease (HD) was analyzed in 222 patients who attained a complete remission (CR) with alternating chemotherapy combinations. Mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) or MOPP/ABV alternating with the lomustine, melphalan, and vindesine combination (MOPP/ABV/CAD) were similarly effective in inducing a CR in 222 of 270 (83%) patients. These patients were scheduled to receive consolidative RT to bulky disease or other critical sites of initial nodal involvement to a total dose of 2,000 cGy, with an optional additional boost of 1,000 cGy. However, only 125 (56%) patients received radiation to all initial nodal sites of disease. In 69 (31%) patients, only selected nodal sites were included in the radiation fields, and 28 (13%) did not receive any RT. Of the 222 CR patients, 42 (19%) relapsed during a median follow-up period of 6.5 years (range, 2 to 15 years). Of these, 26 (62%) patients relapsed exclusively in unirradiated nodal sites, six (14%) within irradiated sites, and 10 (24%) both within and outside irradiated fields. The actuarial 10-year relapse-free survival (RFS) and overall survival (OS) for patients receiving radiation to all initially involved nodal sites were 89% and 94%, respectively, compared with 68% and 71% (P less than .0001) for patients who had only partial or no RT. Cox proportional hazards regression analysis showed that RT to all sites of initial disease was the most significant independent covariate (P less than .005) affecting RFS and OS. These data demonstrate that residual microscopic disease is relatively frequent in patients with apparent CR after alternating combination chemotherapy, and that irradiation of all sites of initial nodal involvement decreases relapse and improves survival in advanced-stage HD.     

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.     

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.     

Radiation dose selection in Hodgkin's disease patients with large mediastinal adenopathy treated with combined modality therapy

PURPOSE: To determine the effective dose of consolidation radiation in Hodgkin's disease (HD) patients with large mediastinal adenopathy (LMA) treated with combined modality therapy (CMT). METHODS AND MATERIALS: Eighty-three HD patients with LMA receiving CMT between 1983 and 1997 at Duke University and Yale University were identified. Patients underwent complete clinical staging. The staging breakdown was: IA, 4 patients; IB, 1 patient; IIA, 25 patients; IIB, 33 patients; IIIA, 3 patients; IIIB-6 patients; IVA, 2 patients; and IVB, 9 patients. All patients received induction chemotherapy (CT) as follows: MOPP/ABV(D), 31 patients; BCVPP, 15 patients; ABVD, 24 patients; MOPP, 3 patients; and other regimens, 10 patients. Following 6 cycles of CT, patients were restaged and classified as having either complete response (CR) or induction failure (IF). Post-CT gallium scans were obtained in 52 patients. Patients with residual radiographic abnormalities were classified as having CR if they were gallium-negative and clinically well otherwise. Following induction CT, 78 patients had a CR. There were 5 IFs. Consolidation irradiation was administered to all sites of initial involvement in patients who had achieved CR. RT dose varied. Patients were grouped into the following dose ranges: < or = 20 Gy, 12 patients; 20-25 Gy, 24 patients; 25-30 Gy, 30 patients; > or = 30 Gy, 12 patients. RESULTS: Overall survival and failure-free survival were both 76% at 10 years. Of the 78 CR patients, 15 failed. Patterns of failure were in-field alone, 8 patients; out of field alone, 2 patients; and combined, 5 patients. Failure patterns by RT dose were: < or = 20 Gy, 0/12; 20-25 Gy, 7/24; 25-30 Gy, 5/30; > or = 30 Gy, 3/11. There was no apparent correlation between RT dose and subsequent failure. Post chemotherapy gallium scans were helpful in predicting for failure. Of 48 patients in whom the gallium was negative after chemotherapy, there were 6 failures, compared with 9 failures among 30 patients in whom gallium was not done after chemotherapy (p = 0.066). Additionally, patients receiving adriamycin-based chemotherapy regimens had improved outcomes compared to those not receiving adriamycin (p = 0.03.) CONCLUSIONS: These retrospective data suggest that low-dose radiotherapy following CR achieved with induction chemotherapy (particularly when documented with gallium scanning) may be as effective as higher doses for bulky HD at presentation. Phase III trials are necessary for confirmation of this hypothesis.     

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.     

Stages I--III Hodgkin's disease in children: results of staging and treatment.

Fifty-two children with clinical stages I-III Hodgkin's disease were evaluated for disease extent between April 1969 and March 1975. All underwent laparotomy and splenectomy. Two patients with liver involvement were excluded. Thirty of 31 patients with pathologically staged IA-IIA disease have been continuous complete remission after mantle and para-aortic irradiation. There have been no extensions into the untreated pelvis. Fourteen of 15 patients with pathologic stages IIB and IIIB disease show no evidence of relapse after TNI and MOPP. Three of four patients with stage IIIA disease developed nodal relapse after irradiation; all are alive without evidence of disease after re-irradiation (3) and MOPP (2). Thus 45 of 50 patients (90%) have remained continuously free of disease after completion of the planned treatment, and overall 49 of 50 (98%) are alive, without evidence of disease. Such results justify continuation of our staging and treatment philosophy in children with Hodgkin's disease.     

The role of radiation therapy in Hodgkin disease: experience and controversy. The 54th annual Janeway Lecture: 1989.

BACKGROUND. Beginning in 1970, a series of patients with Hodgkin disease were treated at the University of Minnesota, after staging laparotomy, with radiation therapy (RT) for Stage I, II, and IIIA Hodgkin disease. This report is an analysis of the results of the treatment and of treatment modifications. METHODS. From 1970 to 1974, all patients were treated with standard RT. In 1975, an analysis of these patients indicated that patients with large mediastinal mass (LMM) and patients with Stage IIIA spleen-positive (IIIAS+) disease had a higher recurrence rates than patients without these factors. Subsequently, a schema of radical radiation therapy (RRT) was devised, which included low-dose lung RT for patients with LMM and low-dose liver RT for patients with IIIAS+ disease. RESULTS. Analysis of the results of the two treatments indicates that the use of low-dose lung RT in patients with LMM and low-dose liver RT in patients with IIIAS+ Hodgkin disease produced survival and recurrence-free survival results equivalent to those achieved by use of combined modality treatment (CMT) or chemotherapy (CT) alone. CONCLUSIONS. The use of RT with whole lung and liver irradiation for patients with LMM and IIIAS+ Hodgkin disease, respectively, produces results that are equivalent to those of CMT or CT alone with the advantage of a decreased incidence of second malignant neoplasms. In addition, patients who do not respond to initial RT have a greater chance of being saved with chemotherapy than do patients initially treated with CMT of being saved with RT. The authors suggest that radical RT is the treatment of choice for patients with LMM and/or IIIAS+ Hodgkin disease.     

Hodgkin's disease in children. Results of therapy in a mixed group of 178 clinical and pathologically staged patients over 13 years

One hundred seventy-eight previously untreated children with biopsy-proven Hodgkin's disease of clinical Stages I and II were treated and followed between 1965 and 1978. Staging laparotomy was performed in 30 patients. Ninety-four percent of the patients obtained a complete remission; 24 patients have died. The actuarial survival rate for all patients was 90% at 5 years, and 81% at 10 years. The disease-free survival rate was 69% at 5 years, and 65% at 10 years. When nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) chemotherapy was added to either extended field or involved field irradiation, the relapse rate was significantly decreased as compared with the protocols without MOPP and prophylactic para-aortic irradiation. The authors believe that surgical staging may not be necessary as splenic involvement may be treated in some patients by MOPP chemotherapy alone or in association with splenic paraaortic radiotherapy. However, the side effects of MOPP need further study by other chemotherapy programs.     

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.     

Prognosis of bulky Hodgkin's disease treated with chemotherapy alone or combined with radiotherapy

The medical records of 396 consecutive patients with a histological diagnosis of Hodgkin's disease were reviewed to assess the prognostic importance of bulky and non-bulky lymphomas. The presence of large lymphadenopathy failed to affect significantly the seven-year results in terms of complete remission (bulky 81.1% v. non-bulky 86.2%), freedom from progression (60.7% v. 65.6%), relapse-free survival (75.1% v. 76.5%) and overall survival (62.7% v. 68.9%). It is noteworthy that in all subsets, ABVD (Adriamycin + bleomycin + vinblastine + dacarbazine), either combined with irradiation or alternated with MOPP (mechlorethamine + vincristine + procarbazine + prednisone), yielded superior results compared with MOPP with or without irradiation. Given the prognostic importance of various bulky sites, the presence of large lymphadenopathy in anatomic regions other than the mediastinum failed to affect results adversely. On the contrary, in patients in stages IIB-IIIA-IIIB, treated with combined modality, the presence of bulky mediastinal involvement did influence prognosis compared with patients with positive but non-bulky mediastinum. At seven years the results were 60.2% v. 79.9% for freedom from progression, 73.2% v. 89.9% for relapse-free survival and 64.8% v. 87.1% for total survival, respectively (P less than 0.03). By contrast, in patients with stage IV disease the extent of mediastinal involvement did not affect results. Nonetheless, the frequency of intrathoracic relapses was higher (26.7%) in patients given chemotherapy alone compared with patients treated with combined modality (11.5%).     

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.     

Radical radiation therapy in the treatment of laparotomy staged Hodgkin's disease patients

In 1970, a policy for the treatment of Stage IIIA Hodgkin's disease patients at the University of Minnesota, which included complete staging procedures and extended field or total nodal irradiation (TNI), was introduced. Evaluation of the results 4 years later indicated that certain patients, especially those with large mediastinal masses and/or hilar disease, or who were spleen positive, were having higher recurrence rates than patients without these characteristics. In 1974, a new approach to treatment for patients with large mediastinal masses or spleen positive disease was instituted which involved treating the whole lung or hemi lung in patients with large mediastinal masses and/or hilar disease, and the liver in patients who had positive spleens. The results of this treatment modification are reported in this study. Long term follow-up reveals that this approach has led to a recurrence free survival and overall survival similar to that noted in patients treated with combined modality treatment without the obvious risk of subsequent leukemia related to combination chemotherapy and radiotherapy. In addition, the complications of the treatment are tolerable and do not demonstrate an increase over patients not treated in this manner. Radical radiation therapy is recommended as a treatment of choice for Stage IA, IIA, and IIIA patients with or without splenic involvement, and with or without hilar disease and/or large mediastinal masses with appropriate radiation field modification to adjust for disease extent.     

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.     

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.     

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.