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.     

Improved survival in hodgkin's disease.

All patients below the age of 66 whose Hodgkin's disease was treated at the Massachusetts General Hospital between July 1, 1965 and June 30, 1973 were analyzed. The patients were divided into an early group seen before November 1, 1968 and a later group seen after that date. Survival and survival without recurrence were calculated by the actuarial method of Berkson and Gage, and compared with figures obtained from a historical series seen at this institution between 1948 and 1964. In the most recent period (1969-1973), 87% of patients with all stages of Hodgkin's disease were alive five years after diagnosis, a remarkable improvement over the 65% survival of the 1965-1968 group and the 34% survival of the historical series. The excellent survival of the recent group was a result of improved management of patients with advanced disease (Stages III and IV), most plausibly attributed to better appreciation of the extent of disease by surgical staging and to the shift from total nodal irradiation to combination chemotherapy for initial treatment of these patients. Recurrence after irradiation was extremely uncommon in patients in Stage IA and IIA (lymphangiogram-negative, asymptomatic) subjected to aging laparotomy, while similarly staged and irradiated patients in Stages IB and IIB (lymphangiogram-negative, symptomatic) did much less well. Except for the surgically staged patients in Stages IA and IIA, the continuing high relapse rate indicates that five-year survival, even when relapse-free, is not synonymous with cure, and emphasizes the need for caution in predicting the ultimate cure rate with current therapy.     

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.     

Long-term results of a randomised trial of involved field radiotherapy vs extended field radiotherapy in stage I and II Hodgkin lymphoma

Involved field (IF) radiation was compared with extended field (EF) radiation in Hodgkin lymphoma (HL) to ascertain whether reduced radiation fields would reduce the late sequelae of radiation without compromising disease control and survival. A total of 603 patients with stage I or II HL were entered into this trial; laparotomy was carried out in 380 (63%) patients. Stage I or IIA disease patients were randomised to receive IF or EF comprising a mantle or inverted Y fields alone. Stage I and IIB patients were randomised between mantle or inverted Y fields and total nodal irradiation (TNI). The dose was 35 Gy to uninvolved sites and 40 Gy to involved sites. The median followup of surviving patients was 25.2 years with only 3.3% lost to follow-up. The treatment failure rate at 25 years in stage IA and IIA was 44% after EF and 54% after IF (P = 0.01); in stage I and IIB this was 80% (EF) and 82% (TNI) at 25 years. No difference in overall survival between the randomised groups was seen. The incidence of second malignancies was 21% after IF and 20% after EF with a slight excess of lung cancer in the EF group. No significant differences in the causes of death between the randomised arms have emerged. In conclusion, IF radiotherapy for stage I and IIA HL results in a 11% greater risk of relapse compared with EF but has no effect on overall survival, risk of second malignancy or cause of death at 25 years.     

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.     

Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease.

PURPOSE: The management of early-stage Hodgkin's disease in the United States is controversial. To evaluate whether staging laparotomy could be safely avoided in early-stage Hodgkin's disease and whether chemotherapy should be a part of the treatment of nonlaparotomy staged patients, a phase III intergroup trial was performed. PATIENTS AND METHODS: Three hundred forty-eight patients with clinical stage IA to IIA supradiaphragmatic Hodgkin's disease were randomized without staging laparotomy to treatment with either subtotal lymphoid irradiation (STLI) or combined-modality therapy (CMT) consisting of three cycles of doxorubicin and vinblastine followed by STLI. RESULTS: The study was closed at the second, planned, interim analysis because of a markedly superior failure-free survival (FFS) rate for patients on the CMT arm (94%) compared with the STLI arm (81%). With a median follow-up of 3.3 years, 10 patients have experienced relapse or died on the chemoradiotherapy arm, compared with 34 on the radiotherapy arm (P <.001). Few deaths have occurred on either arm (three deaths on CMT and seven deaths on STLI). Treatment was well tolerated, with only one death on each arm attributed to treatment. CONCLUSION: These results demonstrate that it is possible to obtain a high FFS rate in a large group of stage IA to IIA patients without performing staging laparotomy and that three cycles of chemotherapy plus STLI provide a superior FFS compared with STLI alone. Extended follow-up is necessary to assess freedom from second relapse, overall survival, late toxicities, patterns of treatment failure, and quality of life.     

Are pelvic irradiation and routine staging laparotomy necessary in clinically staged IA and IIA Hodgkin's disease?

Thirty-nine patients with clinically staged IA and IIA Hodgkin's disease were treated with mantle plus paraaortic/splenic irradiation between 1968 and 1975. All patients had supradiaphragmatic presentations, and none had staging laparotomies. With a follow-up time of 1 to 9 years, mean 4.3 years, the overall relapse-free survival is 92% (100% for stage IA and 89% for stage IIA). The absolute relapse-free 5-year survival is 91% There were no pelvic recurrences. These data show that routine staging laparotomy and pelvic irradiation are not indicated for clinically staged IA and IIA Hodgkin's disease with supradiaphragmatic presentation. The criteria for staging laparotomy in early-stage Hodgkin's disease are discussed.     

Long-term follow-up of patients treated with primary radiotherapy for supradiaphragmatic Hodgkin's disease at St. Jude Children's Research Hospital.

OBJECTIVE: To assess disease control, patterns of relapse, factors predictive of relapse, and late effects of treatment, we reviewed all cases of supradiaphragmatic (SD) Hodgkin's disease (HD) treated with primary radiation therapy (RT) at our institution. METHODS: We retrospectively reviewed the disease characteristics, treatment history, and long-term outcome of the 106 patients with Stage I and II supradiaphragmatic HD who received definitive irradiation at St. Jude Children's Research Hospital between 1970 and 1995. As of the date of analysis, 95 patients are alive, with a median follow-up of 13.3 years (range, 1.9-24.2 years). RESULTS: The median age at diagnosis was 14.7 years (range, 3.7-22.7). Involved-field RT was given to 13 patients (12%), whereas 37 (35%) had mantle RT, 51 patients (48%) had subtotal nodal irradiation, and 5 (5%) had total nodal irradiation. Relapsed disease developed in 26 patients at a median of 1.8 years (range, 0.2-9.3 years). The 5- and 10-year estimated cumulative incidences of relapse were 20.9% +/- 4.0% and 25.1% +/- 4.3%, respectively. With a median dose of 36 Gy (range, 32-40), in-field failure rate was 6.2%, whereas subdiaphragmatic relapse in sites irradiated prophylactically was 1.5%. There was a trend toward an increased incidence of relapse with higher ESR (p = 0.088) and greater number of sites of disease (p = 0.087). Age, stage, histology, nodal disease > or = 6 cm, the presence of bulky mediastinal disease, and the method of staging did not affect the incidence of relapse. The pattern of failure could not be predicted based on the stage of disease, the extent of subdiaphragmatic staging, the extent of radiation therapy, or the sequence of RT fields-"ping pong" vs. sequential. Subset analysis of Stage II patients revealed significantly more relapses in clinically staged patients. Excluding Stage IA patients with high cervical disease or peripheral nodal disease, nodal extension failures were more common for patients undergoing limited-volume RT, whereas extranodal relapses were likely after STNI or TNI. The estimated 10- and 15-year cumulative incidences of second malignancies were 2.9% +/- 1.6% and 7.9% +/- 3.3%, respectively. Our patients are at increased risk of second malignancies (11-fold), and fatal cardiac (68-fold) and infectious (33-fold) complications. Overall survival at 10 years was 90.8% +/- 3.2%; event-free survival was 72.1% +/- 5.0%. CONCLUSIONS: The current analysis confirms the curative potential of RT for HD in children and adolescents. Despite successful salvage therapy, relapsed disease remained the principal cause of death in our cohort. Excess risk of septic death in asplenic patients, fatal heart disease, and second malignancies may further compromise the ultimate cure of HD in long-term survivors.     

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.     

Outcome analysis of localized gastrointestinal lymphoma treated with surgery and postoperative irradiation

One hundred thirteen patients with localized gastrointestinal lymphoma treated by surgery and postoperative irradiation between 1967 and 1985 were reviewed. At 15 years, actuarial survival of this group was 40.6%, with a cause-specific survival of 69.2% and a relapse-free rate of 64%. Two-thirds of relapses occurred at distant sites. In Stage IA and IIA patients with no residuum or with positive resection margins, (N = 90) only site of involvement and stage predicted for relapse. Age, histologic subtype group, and depth of bowel wall invasion did not affect relapse risk. In the very favorable group (Stage IA, IIA, no residuum or microscopic residuum), 8.4% of patients with stomach lymphoma relapsed compared to 25% of patients with small bowel lymphoma. The risk of early relapse was higher in those with Stage IIA small bowel lymphoma than those with Stage IA small bowel lymphoma. We continue to recommend adjuvant abdominal irradiation for patients with Stage IA, IIA completely resected stomach lymphoma and Stage IA completely resected small bowel lymphoma. We recommend combined modality therapy for patients with completely resected Stage IIA small bowel lymphoma and all other localized gastrointestinal lymphoma where visible residual disease is present.     

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.     

Hodgkin's disease stages IA and IIA. A long-term follow-up study on the gains achieved by modern therapy

One hundred forty-nine supradiaphragmatic Stage IA and IIA Hodgkin's disease (HD) patients treated according to one of two different policies, were analyzed to quantitate the therapeutic gains achieved in recent years. Forty-nine patients were managed according to the pre-1969 policy consisting of mantle radiotherapy (XRT) only without laparotomy staging and without subdiaphragmatic treatment. These cases constitute the old series (OS). Ninety-eight patients after 1969 received staging laparotomy-splenectomy and were treated with total or subtotal nodal irradiation, and in a small number also multiagent chemotherapy (MAC). These patients constitute the new series (NS). All prelaparotomy IA and IIA cases are included in the NS even if they became Stage III at laparotomy. Salvage therapy for relapsing disease differed between the OS and NS. The majority of OS relapsing patients received salvage XRT, while the majority of relapsing NS patients received MAC. The NS and OS patient groups are comparable by pretreatment parameters. There is a large and statistically significant improvement in disease-free survival (DFS) and survival (S) in the NS over the OS. At 13 years the NS group had a DFS of 65% compared to 38% in the OS, and S in the NS was 82% compared to 37% in the OS. The improvement in DFS is almost totally due to the addition of prophylactic periaortic XRT in the NS patients. A striking reversal of relapse patterns for the OS and NS was observed. Periaortic nodal relapse occurred in 37% of the OS patients and accounted for 64% of all relapses, while in the NS this failure pattern occurred in only 2% of all cases. Supradiaphragmatic relapse accounted for 74% of all relapses in the NS. Improved salvage of relapsed patients in the NS further added to the overall gain in survival. Whereas no relapsed patient in the OS achieved long-term survival (14% at 10 years, 0 at 25 years), one-half of NS relapses were salvaged by MAC (54% survival at 10 years from relapse). These data clearly document the striking therapeutic gains in Stage IA and IIA supradiaphragmatic HD resulting from the use of prophylactic periaortic XRT and MAC salvage for relapsing patients.     

Total skin electron beam and total nodal irradiation for treatment of patients with cutaneous T-cell lymphoma

Sixteen patients with advanced cutaneous T-cell lymphoma (CTCL) with or without lymph node involvement, but without evidence of extranodal manifestations, were treated with a combination of total skin electron beam therapy (TSEB) and total nodal irradiation (TNI). Fourteen (87%) patients achieved a complete response (CR) lasting from 1 to 84+ months (median, 8+ months) from the completion of treatment. The best results occurred in 6 patients with pretumorous intracutaneous CTCL (Stages IB and IIA) where the CR has lasted in all patients from 8 to 84+ months (median about 27+ months). Conversely, a long-term CR occurred in only one of five patients with tumor-phase intracutaneous CTCL (Stage IIB) and in none of the 5 patients with histopathologically proven nodal involvement (Stage IVA). Radiotherapy was well tolerated with the major toxicity being bone marrow suppression. We conclude that combined TSEB and TNI is a relatively safe and effective treatment for patients with CTCL prior to the development of lymph node involvement. Long-term follow-up is needed to assess the curative potential of this treatment.     

The impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity in early-stage Hodgkin's disease

A retrospective analysis of patients with supradiaphragmatic Stage I-II Hodgkin's disease was performed to assess the impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity. One hundred twenty patients were treated with radiotherapy (RT) alone; 38 received total nodal (including pelvic) irradiation (TNI), 63 received modified total nodal (excluding pelvic) irradiation (MTNI), and 19 received involved-field or mantle irradiation only (less than MTNI). Thirty-three patients received combined-modality therapy. In laparotomy-staged (PS) patients treated with RT alone, the overall treatment failure rate was 13% after TNI, 24% after MTNI, and 43% after less than MTNI. The pelvic failure rate in PS patients was 0% after TNI, 9% after MTNI, and 29% after less than MTNI. Cause-specific deaths in patients treated with RT alone occurred in 10% following less than MTNI, 13% following MTNI, and 10% following TNI. Cause-specific deaths due to pelvic failure in patients treated with RT alone occurred in 5% following IF and 6% following MTNI, and also occurred in 7% of patients receiving combined-modality therapy. The potential disadvantages of elective pelvic irradiation in early-stage Hodgkin's disease include compromise of future tolerance of chemotherapy in the event of treatment failure, and infertility. Gonadal function was assessed in 67 patients less than 35 years old at the time of treatment. Compromise of gonadal function was correlated with the lack of special testicular shielding during pelvic irradiation and chemotherapy in the male, and with no oophoropexy before pelvic irradiation in the female. Twelve of 26 patients with recurrence after either less than MTNI or MTNI, with or without chemotherapy, were alive and without evidence of disease at greater than 2 years after completing salvage therapy, compared with 7 of 11 patients with recurrence after TNI.     

Management of subdiaphragmatic early-stage Hodgkin's disease

Twenty-six patients with Stage IA-IIB Hodgkin's disease confined below the diaphragm were treated at the Mayo Clinic over a 9-year period (1974-1982). Ten of the twenty-six patients presented with intra-abdominal disease alone, and the remaining 16 patients presented with palpable inguinal-femoral adenopathy. One hundred thirty patients with pathologically staged supradiaphragmatic disease were treated over the same period and serve as a comparison group. The median age of 52 years among patients with subdiaphragmatic disease was significantly higher than the median age of 27 years in supradiaphragmatic group. There was no difference in sex distribution between the two groups. One-fifth of the subdiaphragmatic patients presented with B symptoms compared to one-tenth in the supradiaphragmatic group. No significant histological differences were seen. The majority of patients were treated with radiation therapy alone. The overall failure rate was 42% in the subdiaphragmatic group versus 22% in patients with supradiaphragmatic disease. All of the failures occurred in patients treated with radiotherapy alone. Stage and the presence of B symptoms were the most important prognostic factors. The type of subdiaphragmatic presentation (intra-abdominal versus inguinal-femoral) did not influence the outcome. Despite decreased 5-year recurrence-free survival (57% subdiaphragmatic vs. 79% supradiaphragmatic, p = 0.03), the overall 5-year survival rate of 85% is comparable to that of patients with supradiaphragmatic disease. It appears that inverted Y irradiation alone is sufficient for patients with Stage IA disease, but that patients with B symptoms or Stage II disease require more aggressive initial therapy if recurrence-free survival is to be improved.     

Correlation between radiation dose and tumor recurrence and complications in carcinoma of the uterine cervix: stages I and IIA.

A retrospective analysis is reported on 330 patients with carcinoma of the uterine cervix, 23 with Stage IA, 233 with Stage IB and 74 with Stage IIA disease treated with irradiation alone. The dose of irradiation delivered to the cervix, paracervical tissues or the pelvic lymph nodes was correlated with tumor control. There were no central or parametrial failures in patients with Stage IA disease. There were 4 local or marginal (central) recurrences (1.6%) and 15 (6.5%) parametrial failures in the patients with Stage IB disease. Of 74 patients with Stage IIA disease, 3 developed cervical failures (3.9%) and 4 had both central and parametrial recurrences (5.2%).A definite correlation was found between the dose of irradiation delivered to the pelvic lymph nodes and the incidence of recurrences in the patients with Stage IB disease, (about 20%) parametrial failures with doses below 4000 rad in contrast to about 5% with 4000–5000 rad and 2% with doses over 6000 rad). Among patients with Stages IB and IIA disease, the survival of those who were treated with radiation alone and who received doses less than 4000 rad was about 10% less than patients who were treated with higher doses. This difference is not statistically significant; however, it suggests strongly that higher doses of irradiation to the parametria correlate with better tumor control in the pelvis and survival. Complications were slightly higher with doses to the bladder or rectum over 8000 rad. Although it was not statistically significant, patients who had non-standard intracavitary insertions had approximately 18% complications in contrast to only 6.6% in 135 patients with adequate insertions. Factors other than total dose of irradiation, such as geometry of the pelvis, characteristics of the tumor, position of the applicator, type of applicators used, loading and dose rate are important in evaluating the effects of irradiation in tumor control and complications of carcinoma of the uterine cervix.     

ABVD plus radiotherapy versus EVE plus radiotherapy in unfavorable stage IA and IIA Hodgkin's lymphoma: results from an Intergruppo Italiano Linfomi randomized study.

BACKGROUND: In 1997, the Intergruppo Italiano Linfomi started a randomized trial to evaluate, in unfavorable stage IA and IIA Hodgkin's lymphoma (HL) patients, the efficacy and toxicity of the low toxic epirubicin, vinblastine and etoposide (EVE) regimen followed by involved field radiotherapy in comparison to the gold standard doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) regimen followed by the same radiotherapy program. PATIENTS AND METHODS: Patients should be younger than 65 years with unfavorable stage IA and IIA HL (i.e. stage IA or IIA with bulky disease and/or subdiaphragmatic disease, erythrocyte sedimentation rate higher than 40, extranodal (E) involvement, hilar involvement and more than three involved lymph node areas). RESULTS: Ninety-two patients were allocated to the ABVD arm and 89 to the EVE arm. Complete remission (CR) rates at the end of treatment program [chemotherapy (CT) + RT] were 93% and 92% for ABVD and EVE arms, respectively (P = NS). The 5-year relapse-free survival (RFS) rate was 95% for ABVD and 78% for EVE (P < 0.05). As a consequence of the different relapse rate, the 5-year failure-free survival (FFS) rate was significantly better for ABVD (90%) than for EVE (73%) arm (P < 0.05). No differences in terms of overall survival (OS) were observed for the two study arms. CONCLUSIONS: In unfavorable stage IA and IIA HL patients, no differences were observed between ABVD and EVE arms in terms of CR rate and OS. EVE CT, however, was significantly worse than ABVD in terms of RFS and FFS and cannot be recommended as initial treatment for HL.     

Total skin electron beam and total nodal irradiation of cutaneous T-cell lymphoma

Nineteen patients with cutaneous T-cell lymphoma (CTCL) limited to the skin and/or lymph nodes were treated at Hahnemann University with a combination of total skin electron beam and total nodal irradiation (TSEB + TNI). The patients were classified as Stage Ib (1 patient), Stage IIa (8 patients), Stage IIb (5 patients), and Stage IVa (5 patients). Treatment resulted in a complete response in 100% (14/14) of patients with Stage Ib, IIa, and IIb disease, and a CR in 60% (3/5) of patients with Stage IVa disease. The Stage Ib and IIa patients had an overall survival of 100% and a disease-free survival of 44% at 6 years. Four of the five patients with Stage IIb CTCL relapsed within 3 months after completing TSEB + TNI with an overall survival in the group of 40% at 5 years. The Stage IVa patients all relapsed within 7 months and died of their disease within 50 months of completing treatment. The acute effects of TSEB + TNI were well tolerated, but three patients developed second malignancy (lung, kidney and skin) and one patient developed myelodysplasia, possibly the result of radiotherapy.     

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.