VAMP and low-dose, involved-field radiation for children and adolescents with favorable, early-stage Hodgkin's disease: results of a prospective clinical trial.

PURPOSE: To evaluate outcome and assess toxicity of children and adolescents with early-stage, favorable Hodgkin's disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and low-dose, involved-field radiation. PATIENTS AND METHODS: One hundred ten patients with clinical stages I and II, favorable (nonbulky) Hodgkin's disease were treated with four cycles of VAMP chemotherapy and 15 Gy involved-field radiation for those who achieved a complete response, or 25.5 Gy for those who achieved a partial response to two cycles of VAMP. RESULTS: With a median follow-up of 5.6 years (range, 1.1 to 10.4 years), the 5-year survival and event-free survival were 99% (lower confidence limit [CL], 97.4%) and 93% (lower CL, 88.6%), respectively. Factors associated with event-free survival of 100% were complete response to two cycles of VAMP and histology other than nodular sclerosing Hodgkin's disease (NSHD). No serious early or late toxicity has been observed. Patients presenting with clinical stages I and IIA, nonbulky disease involving fewer than three nodal sites have a projected survival and event-free survival of 100% and 97% (lower CL, 93%), respectively, at 5 years. CONCLUSION: Risk-adapted, combined-modality therapy using only four cycles of VAMP chemotherapy with 15 to 25.5 Gy of involved-field radiation for patients with early-stage/favorable Hodgkin's disease is highly effective and without demonstrable late effects. These results indicate that pediatric patients with stages I and II favorable Hodgkin's disease can be cured with limited therapy that does not include an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiation therapy.     

What is the optimal treatment volume in Hodgkin's disease patients undergoing high-dose chemotherapy and adjuvant radiation therapy?

To determine the optimal treatment volume in Hodgkin's disease patients undergoing high-dose chemotherapy (HDCT) and radiation therapy (RT), failure sites were reviewed in 56 patients. Twenty-one (38%) received involved-field RT (IFRT) before or after HDCT encompassing sites of prior disease. Failure sites were designated as previously involved (old) or uninvolved (new) sites. Seven patients (12%) died in the immediate post-HDCT period, leaving 49 evaluable (median follow-up, 41 months). Twenty-five patients (51%) relapsed (14 HDCT, 11 HDCT + IFRT): seven (28%) in old, eight (32%) in new, and ten (40%) in old and new sites. Six of the seven who relapsed in old sites received HDCT alone, whereas seven of the eight who relapsed in new sites received IFRT. Relapse in old sites was particularly common in patients failing to achieve a complete response. The most common new failure site was nodal, occurring in 11 patients and was primarily (10/11) adjacent to an old site. Although it controls prior disease, IFRT is insufficient in Hodgkin's disease patients undergoing HDCT. Relapse is common in new nodal sites and is primarily adjacent to prior sites. These results suggest that extended-field RT encompassing old and adjacent uninvolved nodal sites may be the optimal treatment volume in these patients.     

Analysis of treatment results in advanced Hodgkin's disease: the case for adjuvant radiotherapy

PURPOSE: To assess the treatment results in patients with advanced Hodgkin's disease in a single center and to evaluate the clinical and therapeutic prognostic factors, including verification of the significance of the prognostic score. METHODS AND MATERIALS: Treatment results were analyzed in 133 patients with newly diagnosed Stage IIIB and IV Hodgkin's disease. Treatment consisted of six courses of hybrid chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone [MOPP]/doxorubicin (adriamycin), bleomycin, and vincristine [ABV]) followed by irradiation (RT) in patients with an indication for RT (84 patients). Chemotherapy was then continued for another two cycles. The indications for consolidation RT included bulky disease and/or partial response after six cycles of chemotherapy. In 31 patients, extended-field RT was performed, and in 53, limited fields were irradiated. The median radiation dose was 39 Gy. RESULTS: The median follow-up was 78 months. Complete remission after whole treatment was achieved in 88.7% of patients. The actuarial overall survival rate was 78% and 71%, and relapse-free survival rate was 73% and 65% at 5 and 10 years, respectively. The independent adverse prognostic factors in multivariate analysis appeared to be older age, low serum albumin, low serum gammaglobulin, lower number of chemotherapy cycles, and no RT. The value of the prognostic score was confirmed; the higher the prognostic score, the worse the survival. CONCLUSION: In patients with advanced Hodgkin's disease, consolidation RT improved survival. The best results were achieved with the use of large-volume RT.     

Poorer outcome of elderly patients treated with extended-field radiotherapy compared with involved-field radiotherapy after chemotherapy for Hodgkin's lymphoma: an analysis from the German Hodgkin Study Group.

BACKGROUND: The optimal treatment of elderly patients with Hodgkin's lymphoma (HL) is still a matter of debate. Since many of these patients receive combined modality treatment, we evaluated the impact of different radiation field sizes, that is extended-field (EF) or involved-field (IF) technique when given after four cycles of chemotherapy. PATIENTS AND METHODS: In the multicenter HD8 study of the German Hodgkin Study Group, 1204 patients with early-stage unfavorable HL were randomized to receive four cycles of chemotherapy followed by either radiotherapy (RT) of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B). A total of 1064 patients were assessable for the analysis. Of these, 89 patients (8.4%) were 60 years or older. RESULTS: Elderly patients had a poorer risk profile. Acute toxicity from RT was more pronounced in elderly patients receiving EF-RT compared with IF-RT [World Health Organization (WHO) grade 3/4: 26.5% versus 8.6%)]. Freedom from treatment failure (FFTF, 64% versus 87%) and overall survival (OS, 70% versus 94%) after 5 years was lower in elderly patients compared with younger patients. Importantly, elderly patients had poorer outcome when treated with EF-RT compared with IF-RT in terms of FFTF (58% versus 70%; P = 0.034) and OS (59% versus 81%; P = 0.008). CONCLUSION: Elderly patients with early-stage unfavorable HL generally have a poorer risk profile and outcome when compared with younger patients. Treatment with EF-RT instead of IF-RT after chemotherapy has a negative impact on survival of elderly patients and should be avoided.     

早期霍奇金病综合治疗中受累野照射的临床疗效

目的 评价Ⅰ、Ⅱ期霍奇金病（HD）患者综合治疗时受累野照射的疗效和毒副作用,并与扩大野照射进行比较。方法 早期HD 88例,根据Ann Arbor分期,ⅠA期12例（13．7％）,ⅡA期56例（63．6％）,ⅡB期20例（22．7％）。全部患者接受化疗和放疗综合治疗,先化疗后放疗患者83例,先放疗后化疗患者5例。化疗多采用ABVD或ABVD／MOPP方案;受累野照射42例,扩大野照射46例。结果 全组有6例膈上原发HD治疗后复发,受累野组和扩大野组各3例。扩大野组有1例照射野内复发,受累野组有1例在邻近照射部位的腋窝复发,其余4例患者均表现为结外器官或膈下淋巴结受侵。全组患者1、2、3年总生存率分别为100．0％、98．6％和96．3％,受累野组患者分别为100．0％、97．1％和97．1％,扩大野组患者分别为100．0％、100．0％和95．8％,两组生存率差异无统计学意义（P=0．86）。受累野组1、2、3年无进展生存率分别为97．6％、94．8％和91．7％,扩大野组分别为97．8％、93．2％和93．2％,两组无进展生存率差异无统计学意义（P=0．65）。发生Ⅰ度和Ⅱ度白细胞减少症者,受累野组3例（7．2％）,扩大野组9例（19．5％,P=0．089）。结论 Ⅰ、Ⅱ期HD患者进行综合治疗时,采用受累野照射可获得与扩大野照射相同的疗效,且能减少并发症的发生。     

A meta-analysis of stages I and II Hodgkin's disease

To compare radiotherapy alone to chemotherapy plus radiotherapy in the treatment of early stage Hodgkin's disease, the English language medical literature was searched for reports on randomized clinical trials in Stages I and II Hodgkin's disease from 1975 through 1986. Twenty-three reports with 2999 patients were entered into matched study analysis. Data on extended-field radiotherapy (EF), involved-field (IF), chemotherapy alone, combination chemotherapy and radiotherapy (CM), disease stage, laparotomy staging, and complications were gathered. A proportional hazard rate was used to estimate and compare relapse-free (RFS) and overall survival rates (S). Iteratively reweighted least square analysis was used to estimate survival curves. Twelve-year RFS for CM (889 patients) was significantly superior to EF (1350 patients) (P less than 0.01). Twenty-year RFS in EF was better than IF (760 patients) (P less than 0.01). Twelve-year S for CM was not significantly different than for EF but was better than for IF (P less than 0.05).     

Risk-adapted, combined-modality therapy with VAMP/COP and response-based, involved-field radiation for unfavorable pediatric Hodgkin's disease.

PURPOSE: To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease. PATIENTS AND METHODS: From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or "B" symptoms and all stage III and IV. RESULTS: Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% +/- 2.5% and 75.6% +/- 4.1%, respectively. CONCLUSION: Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease.     

Can elective nodal irradiation be omitted in stage III non-small-cell lung cancer? Analysis of recurrences in a phase II study of induction chemotherapy and involved-field radiotherapy

PURPOSE: To establish the recurrence patterns when elective mediastinal irradiation was omitted, patients with Stage III non-small-cell lung cancer were treated with sequential chemotherapy (CHT) and involved-field radiotherapy (RT). METHODS AND MATERIALS: Fifty patients were treated with either two or four cycles of induction CHT, followed by once-daily involved-field RT to 70 Gy, delivered using three-dimensional treatment planning. The contoured gross tumor volume consisted of the pre-CHT tumor volume and nodes with a short-axis diameter of > or = 1 cm. Patients were reevaluated at 3 and 6 months after RT using bronchoscopy and chest CT. Elective nodal failure was defined as recurrence in the regional nodes outside the clinical target volume, in the absence of in-field failure. RESULTS: Of 43 patients who received doses > or = 50 Gy, 35% were disease free at last follow-up; in-field recurrences developed in 27% (of whom 16% had exclusively in-field recurrences); 18% had distant metastases exclusively. No elective nodal failure was observed. The median actuarial overall survival was 18 months (95% confidence interval 14-22) and the median progression-free survival was 12 months (95% confidence interval 6-18). CONCLUSION: Omitting elective mediastinal irradiation did not result in isolated nodal failure. Future studies of concurrent CHT and RT for Stage III non-small-cell lung cancer should use involved-field RT to limit toxicity.     

The residual mediastinal mass following radiation therapy for Hodgkin's disease

Thirty-two patients with mediastinal involvement by Hodgkin's disease (HD), treated with an isocentric technique of extended-field radiation therapy (RT) with or without chemotherapy, are described. Twenty-nine patients (91%) had a complete response to therapy and four patients subsequently relapsed, with a median follow-up of 54 months. Five of seven patients not in continuous complete remission were salvaged, with one additional salvage therapy. Ten patients had persistent mediastinal masses at 1 year, following completion of planned therapy; only one of these has had recurrent disease. Of those who achieved complete response, only one patient has had disease recurrence in the mediastinum. We conclude that extended-field RT, using an isocentric technique, provides excellent local disease control in HD; however, persistent mediastinal widening after therapy is frequent, and additional therapy should not be given in the absence of conclusive evidence of disease progression.     

Prospective study of combined modality treatment or radiotherapy alone in the management of early-stage adult Hodgkin's disease

PURPOSE: To determine the efficacy and toxicity of combined modality treatment (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult Hodgkin's disease patients. METHODS AND MATERIALS: Forty-seven patients with supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky mediastinal lymphadenopathy were enrolled into this prospective study between September 1997 and February 2002. Patients with very favorable criteria presenting with one or two nonbulky nodal areas involved, an erythrocyte sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant or nodular sclerosing histologic findings were treated by RT alone. Patients missing any of these favorable criteria were classified as the other favorable group and were treated with three courses of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by involved-field RT. The median age was 36 years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men. Only 3 patients were classified as the most favorable group and treated with mantle RT alone; the remaining 44 were treated with CMT. RESULTS: The median follow-up was 51 months (range, 20-74 months). Only 2 patients developed recurrence, both out of the irradiated field, one in the contralateral neck and the other in the abdomen. The 5-year relapse-free and overall survival rate was 95.4% and 97.8%, respectively. Although none of the prognostic factors were statistically significant for relapse-free survival, a trend was noted for the response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related complications. One patient treated with mantle RT alone developed severe ischemic heart disease and one in the CMT arm developed subclinical hypothyroidism. CONCLUSION: Despite the short follow-up, CMT or RT alone tailored according to the clinical prognostic factors were successful in terms of disease control in clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make definitive conclusions.     

Occurrence of acute nonlymphocytic leukemia in a prospective randomized study of treatment for Hodgkin's disease

In a prospective randomized study of treatment with radiation therapy (RT) or RT followed by chemotherapy (CT) for patients with Hodgkin's disease stages I-III, four patients developed acute nonlymphocytic leukemia (ANLL) during post-treatment follow-up. There was a significant relationship between the intensity of the treatment and the appearance of this complication: no cases of ANLL were observed among the 128 patients treated with involved field (IF) RT, IF RT followed by CT, total nodal RT alone (TNR), or total lymphoid irradiation alone (TLI) after a follow-up from 21 to 126+ months (median follow-up 76 months). In contrast, four of 36 patients treated with extensive RT followed by CT developed ANLL at 17, 63, 72, and 91 months. Three of these patients had received TLI + CT, the fourth one TNR + CT.     

Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials.

BACKGROUND: Despite several investigations, second malignancy risks (SMR) following radiotherapy alone (RT), chemotherapy alone (CT) and combined chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial. PATIENTS AND METHODS: We sought individual patient data from randomised trials comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF) versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of salvage treatment) were compared using Peto's method. RESULTS: Data for between 53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P = 0.04 and OR = 3.25). CONCLUSIONS: Administration of CT in addition to RT as initial therapy for HL decreases overall SMR by reducing relapse and need for salvage therapy. Administration of RT additional to CT marginally increases overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was substantially higher after EF-RT. Caution is needed in applying these findings to current therapies.     

Upfront chemotherapy and involved-field radiotherapy results in more relapses than extended radiotherapy for intracranial germinomas: modification in radiotherapy volume might be needed

PURPOSE: To retrospectively compare the outcome of upfront chemotherapy plus radiotherapy (CRT) and the outcome of the use of extended radiotherapy (RT) only for intracranial germinoma. METHODS AND MATERIALS: Of 81 patients with tissue-confirmed intracranial germinoma, 42 underwent CRT and 39 underwent RT only. For CRT, one to five cycles of upfront chemotherapy was followed by involved-field or extended-field RT, for which the dose was dependent on the M stage. For RT only, all 39 patients underwent craniospinal RT alone. The median follow-up was 68 months. RESULTS: The 5- and 10-year overall survival rate was 100% and 92.5% for RT alone and 92.9% and 92.9% for CRT, respectively. The 5-year recurrence-free survival rate was 100.0% for RT and 88.1% for CRT (p = 0.0279). No recurrences developed in patients given RT, but four relapses developed in patients who had received CRT -- three in the brain and one in the spine. Only one patient achieved complete remission from salvage treatment. The proportion of patients requiring hormonal replacement was greater for patients who received RT than for those who had received CRT (p = 0.0106). CONCLUSIONS: The results of our study have shown that the better quality of life provided by CRT was compensated for by the greater rate of relapse. The possible benefit of including the ventricles in involved-field RT after upfront chemotherapy, specifically for patients with initial negative seeding, should be addressed in a prospective study.     

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.     

Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin's disease: eight-year update of an Italian prospective randomized study.

PURPOSE: To compare the effectiveness of chemotherapy (CHT) with extended-field radiotherapy (RT) in the treatment of early-stage Hodgkin's disease (ESHD), we report an 8-year updated analysis of a study in which treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) CHT was randomly compared with extended-field RT. PATIENTS AND METHODS: From August 1979 to December 1982, 89 adult patients with pathologic stage I-IIA Hodgkin's disease (HD) were randomly allocated to receive either RT with mantle field followed by periaortic irradiation (n = 45) or six monthly courses of MOPP CHT (n = 44). RESULTS: All patients in the RT arm and 40 of 44 in the CHT arm achieved complete remission. Twelve relapses occurred in each group. Eight patients treated with MOPP and two of the RT arm died of HD. Three other patients of the CHT group died because of a second cancer. With a median follow-up greater than 8 years, the overall survival rate is significantly higher in the RT than in the CHT group (93% v 56%; P less than .001), whereas the rates of freedom from progression and relapse-free survival (RFS) were similar in the two groups (76% v 64% and 70% v 71%, respectively). Of the 12 patients relapsing after RT, 11 (92%) achieved a second CR, compared with only six of the 12 (50%) in the MOPP group. Analysis of the response rate to salvage treatments showed that the type of relapse in the MOPP group was a prognostic indicator for the achievement of a second CR, whereas in the RT group, a second CR was obtained regardless of the characteristics of the relapses. At 80 months, the probability of survival of relapsing patients calculated from time of relapse was 85% and 15% in the RT and CHT groups, respectively (P = .02). CONCLUSION: We conclude that RT alone is the treatment of choice for adult patients with ESHD with favorable prognostic factors.     

ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results.

PURPOSE: Radiation therapy (RT) alone can cure more than 80% of all patients with pathologic stage IA, IB, and IIA Hodgkin's disease, but some prognostic factors unfavorably affect treatment outcome. Combined-modality approaches improved results compared with RT, but the optimal extent of RT fields when combined with chemotherapy warranted additional evaluation. PATIENTS AND METHODS: In February 1990, we activated a prospective trial in patients with early, clinically staged Hodgkin's disease to assess efficacy and tolerability of four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by either subtotal nodal plus spleen irradiation (STNI) or involved-field radiotherapy (IFRT). RESULTS: Main patient characteristics were fairly well balanced between the two arms. Complete remission was achieved in 100% and in 97% of patients, respectively. The 12-year freedom from progression rates were 93% (95% CI, 83% to 100%) after ABVD and STNI, and 94% (95% CI, 88% to 100%) after ABVD and IFRT, whereas the figures for overall survival were 96% (95% CI, 91% to 100%) and 94% (95% CI, 89% to 100%), respectively. Apart from three patients who developed second malignancies in the STNI arm, treatment-related morbidities were mild. CONCLUSION: Present long-term findings suggest that, after four cycles of ABVD, IFRT can achieve a worthwhile outcome. The limited size of our patient sample, however, had no adequate statistical power to test for noninferiority of IFRT versus STNI. Despite this, ABVD followed by IFRT can be considered an effective and safe modality in early Hodgkin's disease with both favorable and unfavorable presentation.     

The intergroup Hodgkin's disease in children. A study of stages I and II

A total of 228 previously untreated and eligible children with pathologic Stage I or II Hodgkin's disease were registered in the Intergroup Study of Hodgkin's Disease in Children between February 1977 and April 1981. Patients were randomized in the Southwest Oncology Group (later the Pediatric Oncology Group [POG] to involved-field (IF) radiotherapy alone or IF radiotherapy followed by six courses of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) chemotherapy; patients in the Children's Cancer Study Group (CCSG) and Cancer and Leukemia Group B (CALGB) were randomized to receive extended-field (EF) radiotherapy or IF radiotherapy followed by six courses of MOPP. An estimated 97% of patients receiving IF + MOPP were relapse-free and surviving (RFS) at 5 years, which was significantly better than 41% for patients receiving IF alone; however there was essentially no overall difference in survival experience between groups. Patients in CCSG and CALGB receiving IF + MOPP had significantly superior RFS at 5 years than patients receiving EF. Survival rate was not different between these two groups, an estimated 93% of patients surviving 5 years or longer. Although patients were not randomized between IF or EF radiotherapy, they were similar with respect to patient characteristics. There was some statistical evidence that RFS was superior at 5 years for patients receiving EF than for IF; however, there was no evidence of a difference in survival experience. The percentages of patients with late effects of therapy were not significantly different by treatment. The most common types of late effects were endocrine dysfunction and impaired resistance to infection. Overall, the response rate to therapy for relapse patients was good, being 83% among all patients who relapsed. Patient characteristics related to poor prognosis were the presence of constitutional (B) symptoms (fever, night sweats, and weight loss) and poor performance status.     

Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's disease: the experience of the French Society of Pediatric Oncology.

PURPOSE: With the aim of decreasing undesirable side effects of therapy, we investigated the reduction of both chemotherapy and radiation therapy (RT) in children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy) after good response to chemotherapy. PATIENTS AND METHODS: A French national study began in 1982 that included 238 pediatric patients with Hodgkin's disease. Initial staging was clinical and without laparotomy. In patients with localized disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP. Patients with more advanced disease (IB-IIB-III-IV) received three courses of MOPP that was alternated with three courses of ABVD. All of the patients who achieved a good remission after chemotherapy were administered 20 Gy RT, which was limited to the initially involved areas for localized disease, and encompassed the paraaortic nodes and the spleen as well for more advanced stages. When a good remission was not obtained, 40 Gy RT was administered. RESULTS: At the completion of chemotherapy, 227 patients (97%) were considered good responders, whereas 11 did not achieve a good remission. With a median follow-up of 6 years, the 6-year actuarial survival was 92% and the disease-free survival was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV patients was discontinued because of poor results. CONCLUSIONS: Present findings indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid therapeutic approach in the vast majority of children with Hodgkin's disease.     

Involved-field radiotherapy for patients in partial remission after chemotherapy for advanced Hodgkin's lymphoma

PURPOSE: The use of radiotherapy in patients with advanced Hodgkin's lymphoma (HL) is controversial. The purpose of this study was to describe the role of radiotherapy in patients with advanced HL who were in partial remission (PR) after chemotherapy. METHODS: In a prospective randomized trial, patients <70 years old with previously untreated Stage III-IV HL were treated with six to eight cycles of mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycine, vinblastine hybrid chemotherapy. Patients in complete remission (CR) after chemotherapy were randomized between no further treatment and involved-field radiotherapy (IF-RT). Those in PR after six cycles received IF-RT (30 Gy to originally involved nodal areas and 18-24 Gy to extranodal sites with or without a boost). RESULTS: Of 739 enrolled patients, 57% were in CR and 33% in PR after chemotherapy. The median follow-up was 7.8 years. Patients in PR had bulky mediastinal involvement significantly more often than did those in CR after chemotherapy. The 8-year event-free survival and overall survival rate for the 227 patients in PR who received IF-RT was 76% and 84%, respectively. These rates were not significantly different from those for CR patients who received IF-RT (73% and 78%) or for those in CR who did not receive IF-RT (77% and 85%). The incidence of second malignancies in patients in PR who were treated with IF-RT was similar to that in nonirradiated patients. CONCLUSION: Patients in PR after six cycles of mechlorethamine, vincristine, procarbazine, prednisone/doxorubicine, bleomycine, vinblastine treated with IF-RT had 8-year event-free survival and overall survival rates similar to those of patients in CR, suggesting a definite role for RT in these patients.     

Long-term results with radiotherapy for stage I–II follicular lymphomas

Purpose: To analyze the long-term results with radiotherapy (RT) for early-stage, low-grade follicular lymphomas.

Methods and Materials: From 1960 to 1988, 80 patients with Stage I (n = 33) or II (n = 47), World Health Organization Grade 1 (n = 50) or 2 (n = 30) follicular lymphoma were treated with RT. The lymph nodes or spleen were involved in 97% of cases. The maximal tumor sizes ranged from 0.5 to 11.0 cm (median 2.0). The RT fields encompassed only the involved Ann Arbor nodal region (involved-field RT) in 9% of the patients. The fields also included 1–3 adjacent, grossly uninvolved nodal regions (regional RT) in 54% of patients but were smaller than mantle or whole abdominopelvic fields. Mantle or whole abdominopelvic fields encompassing up to 6 grossly uninvolved regions (extended-field RT) were used in the remaining 37% of patients. The total RT doses ranged from 26.2 to 50.0 Gy given in daily 1.0–3.0-Gy fractions.

Results: The follow-up of the surviving patients ranged from 3.5 to 28.7 years (median 19.0). No recurrences were found >17.0 years after RT, with 13 patients free of disease at their last follow-up visit 17.6–25.0 years after treatment. In 58% of cases, death was not from follicular lymphoma. The 15-year local control rate was 100% for 44 lymphomas <3.0 cm treated with only 27.8–30.8 Gy (median 30.0 in 20 fractions). Progression-free survival was affected by the maximal tumor size at the start of RT (15-year rate 49% vs. 29% for lymphomas <3.0 cm vs. ≥3.0 cm, respectively, p = 0.04) and Ann Arbor stage (15-year rate 66% vs. 26% for Stages I and II, respectively, p = 0.006). Ann Arbor stage also affected the cause-specific survival (15-year rate 87% vs. 54% for Stages I and II, respectively, p = 0.01). No significant difference was found in overall survival between those treated with extended-field RT and those treated with involved-field RT or regional RT (15-year rate 49% and 40%, respectively, p = 0.51). The 15-year incidence rate of Grade 3 or greater late complications according to the Subjective, Objective, Management, and Analytical scale in patients treated with 26.2–30.8 Gy vs. 30.9–50.0 Gy was 0% and 6%, respectively.

Conclusions: RT can cure approximately one half of Stage I and one quarter of Stage II, World Health Organization Grade 1 or 2 follicular lymphomas. Follicular lymphomas <3.0 cm can be controlled locally with doses of 27.8–30.8 Gy, and there is a trend toward a higher incidence of late complications with doses of >30.8 Gy. Doses of 25–30 Gy delivered in 15–20 fractions should be examined prospectively in patients with follicular lymphomas of <3.0 cm.