Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease. Effect of ABVD chemotherapy with and without mantle or mediastinal irradiation on pulmonary function and symptoms in early-stage Hodgkin's disease. Randomized comparison of consolidation radiation versus observation in bulky Hodgkin's lymphoma with post-chemotherapy negative positron emission tomography scans A prospective clinical trial comparing chemotherapy, radiotherapy and combined therapy in the treatment of early stage Hodgkin's disease with bulky disease. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage I-II Hodgkin's disease. The concept of the GPOH-HD 2003 therapy study for pediatric Hodgkin's disease: evolution in the tradition of the DAL/GPOH studies. Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group. Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. POG 8625: A Randomized Trial Comparing Chemotherapy With Chemoradiotherapy for Children and Adolescents With Stages I, IIA, IIIA1 Hodgkin Disease: A Report from the Children's Oncology Group The EORTC trials for limited stage Hodgkin's disease. The EORTC Lymphoma Cooperative Group. Consolidation radiation after complete remission in Hodgkin's disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need? Randomized trial of CVPP for three versus six cycles in favorable-prognosis and CVPP versus AOPE plus radiotherapy in intermediate-prognosis untreated Hodgkin's disease. Initial chemotherapy and low-dose radiation in limited fields in childhood Hodgkin's disease: results of a joint cooperative study by the French Society of Pediatric Oncology (SFOP) and Hôpital Saint-Louis, Paris. Language bias in randomised controlled trials published in English and German
PURPOSE Current st and ard therapy for children and adolescents with Hodgkin 's disease includes combination chemotherapy and low-dose involved-field radiation ( LD-IFRT ) . Because radiation may be associated with adverse late effects , the Children 's Cancer Group ( CCG ) investigated whether radiation could be omitted in patients achieving a complete response to initial chemotherapy without jeopardizing the excellent outcome obtained with combined-modality therapy . PATIENTS AND METHODS Between January 1995 and December 1998 , 829 eligible patients were enrolled onto CCG 5942 . A total of 501 patients who achieved an initial complete response after risk-adapted combination chemotherapy were r and omized to receive LD-IFRT or no further treatment .  Event-free survival ( EFS ) and overall survival were assessed from the date of study entry or the date of r and omization , as appropriate . RESULTS The projected 3-year EFS from study entry for the entire cohort was 87 % + /- 1.2 % . Among patients who achieved a complete response to initial chemotherapy , 92 % + /- 1.9 % of those r and omized to receive LD-IFRT were alive and disease free 3 years after r and omization , versus 87 % + /- 2.2 % for patients r and omized to receive no further therapy ( stratified log-rank test ; P = .057 ) . With an " as-treated " analysis , 3-year EFS after r and omization for the radiation cohort was 93 % + /- 1.7 % versus 85 % + /- 2.3 % for patients receiving no further therapy ( stratified log-rank test ; P = .0024 ) . Three-year survival estimates for patients treated with and without LD-IFRT were 98 % + /- 1.1 % for patients who received radiation and 99 % + /- 0.5 % for patients who did not receive radiation . CONCLUSION LD-IFRT after an initial complete response to risk-adapted chemotherapy improved EFS . At this time , there is no survival advantage for LD-IFRT , but follow-up remains short PURPOSE To investigate whether combined-modality treatment ( CMT ) with two cycles of doxorubicin , bleomycin , vinblastine , and dacarbazine ( ABVD ) followed by extended-field radiotherapy ( EF-RT ) is superior to EF-RT alone in patients with early favorable Hodgkin 's lymphoma ( HL ) . PATIENTS AND METHODS Between 1993 and 1998 , 650 patients with newly diagnosed , histology-proven HL in clinical stages IA to IIB without risk factors were enrolled onto this multicenter study and r and omly assigned to receive 30 Gy EF-RT plus 10 Gy to the involved field ( arm A ) or two cycles of ABVD followed by the same radiotherapy ( arm B ) . Results At a median observation time of 87 months , there was no difference between treatment arms in terms of complete response rate ( arm A , 95 % ; arm B , 94 % ) and overall survival ( at 7 years : arm A , 92 % ; arm B , 94 % ; P = .43 ) . However , freedom from treatment failure was significantly different , with 7-year rates of 67 % in arm A ( 95 % CI , 61 % to 73 % ) and 88 % in arm B ( 95 % CI , 84 % to 92 % ; P < or= .0001 ) . This was due mainly to significantly more relapses after EF-RT only ( arm A , 22 % ; arm B , 3 % ) . No patient treated with CMT experienced relapse before year 3 . Relapses were treated mainly with bleomycin , etoposide , doxorubicin , cyclophosphamide , vincristine , procarbazine , and prednisone , or with the combination cyclophosphamide , vincristine , procarbazine , and prednisone/ABVD ;  treatment of relapse was significantly more successful in arm A than in arm B ( P = .017 ) . In total , there were 39 second malignancies , with 21 in arm A and 18 in arm B , respectively . The incidence was approximately 0.8 % per year during years 2 to 9 and was highest in older patients ( P < .0001 ) and those with " B " symptoms ( P = .012 ) . CONCLUSION CMT consisting of two cycles of ABVD plus EF-RT is more effective than EF-RT alone PURPOSE In early-stage Hodgkin 's lymphoma ( HL ) , subtotal nodal irradiation ( STNI ) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity . The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy ( IF-RT ) without jeopardizing disease control . PATIENTS AND METHODS Patients with stage I or II HL were stratified into two groups , favorable and unfavorable , based on the following four prognostic factors : age , symptoms , number of involved areas , and mediastinal-thoracic ratio . The experimental therapy consisted of six cycles of epirubicin , bleomycin , vinblastine , and prednisone ( EBVP ) followed by IF-RT . It was r and omly compared , in favorable patients , to STNI and , in unfavorable patients , to six cycles of mechlorethamine , vincristine , procarbazine , prednisone , doxorubicin , bleomycin , and vinblastine ( MOPP/ABV hybrid ) and IF-RT . RESULTS Median follow-up time of the 722 patients included was 9 years . In 333 favorable patients , the 10-year event-free survival rates ( EFS ) were 88 % in the EBVP arm and 78 % in the STNI arm ( P = .0113 ) , with similar 10-year overall survival ( OS ) rates ( 92 % v 92 % , respectively ; P = .79 ) . In 389 unfavorable patients , the 10-year EFS rate was 88 % in the MOPP/ABV arm compared with 68 % in the EBVP arm ( P < .001 ) , leading to 10-year OS rates of 87 % and 79 % , respectively ( P = .0175 ) . CONCLUSION A treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients . In favorable patients , the combination of EBVP and IF-RT can replace STNI as st and ard treatment . In unfavorable patients , EBVP is significantly less efficient than MOPP/ABV PURPOSE Chemoradiotherapy has been considered st and ard treatment for patients with limited-stage aggressive lymphoma on the basis of trials conducted before the introduction of the International Prognostic Index . To evaluate this approach in elderly patients with low-risk localized lymphoma , we conducted a trial comparing chemoradiotherapy with chemotherapy alone . PATIENTS AND METHODS Previously untreated patients older than 60 years with localized stage I or II histologically aggressive lymphoma and no adverse prognostic factors of the International Prognostic Index were r and omly assigned to receive either four cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) plus involved-field radiotherapy ( 299 patients ) or chemotherapy alone with four cycles of CHOP ( 277 patients ) . RESULTS With a median follow-up time of 7 years , event-free and overall survival did not differ between the two treatment groups ( P = .6 and P = .5 , respectively ) . The 5-year estimates of event-free survival were 61 % for patients receiving chemotherapy alone and 64 % for patients receiving CHOP plus radiotherapy ; the 5-year estimates of overall survival were 72 % and 68 % , respectively . In a multivariate analysis , overall survival was affected by stage II disease ( P < .001 ) and male sex ( P = .03 ) . CONCLUSION In this large prospect i ve study , CHOP plus radiotherapy did not provide any advantage over CHOP alone for the treatment of low-risk localized aggressive lymphoma in elderly patients To determine whether combined modality therapy ( CMT ) is superior to chemotherapy ( CT ) alone , 152 untreated Hodgkin disease patients with clinical stages ( CSs ) IA , IB , IIA , IIB , and IIIA without bulk disease were prospect ively r and omized to 6 cycles of doxorubicin , bleomycin , vinblastine , dacarbazine ( ABVD ) alone or 6 cycles of ABVD followed by radiation therapy ( RT ) ( 3600 cGy : involved field for 11 patients , modified extended field for the rest ) . Of 76 patients r and omized to receive RT , 65 actually received it , and 11 did not ( 4 progressed , 1 had bleomycin toxicity , 6 refused ) . For ABVD + RT , the complete remission ( CR ) percentage was 94 % and no major response , 6 % . For ABVD alone , 94 % achieved a CR ; 1.5 % , a partial response ( PR ) ; and 4.5 % , no major response . At 60 months CR duration , freedom from progression ( FFP ) , and overall survival ( OS ) for ABVD + RT versus ABVD alone are 91 % versus 87 % ( P = .61 ) , 86 % versus 81 % ( P = .61 ) , and 97 % versus 90 % ( P = .08 ) , respectively ( log-rank ) . The 95 % confidence intervals for CR duration , FFP , and OS differences at 5 years were -8 % to 15 % , -8 % to 18 % , and -4 % to 12 % , respectively . Although significant differences were not seen , it is possible that a benefit in outcome of less than 20 % for CMT might be seen in a larger trial PURPOSE To evaluate the effect of doxorubicin , bleomycin , vinblastine , and dacarbazine ( ABVD ) chemotherapy alone and of ABVD with mantle or mediastinal irradiation ( RT ) on the pulmonary function of patients with early-stage Hodgkin 's disease . PATIENTS AND METHODS Between 1989 and 1993 , 60 patients with clinical stage I to IIIA HD enrolled onto r and omized trials at Memorial Sloan-Kettering Cancer Center ( MSKCC ) underwent prospect i ve evaluation of pulmonary function . All patients received six cycles of ABVD , and 30 patients received mantle or mediastinal RT .  Pulmonary function tests ( PFTs ) and symptom evaluation were conducted before , during , and after completion of chemotherapy and RT , and at various intervals thereafter . The median follow-up time was 30 months . RESULTS During chemotherapy , symptoms of cough and dyspnea on exertion developed in 32 of 60 patients ( 53 % ) and declines in pulmonary function occurred in 22 of 60 patients ( 37 % ) . Discontinuation of bleomycin was necessary in 14 of 60 patients ( 23 % ) . Following chemotherapy , there was a significant decline in median forced vital capacity ( FVC ) and diffusing capacity of carbon monoxide ( DLCO ) . In patients who received mantle or mediastinal RT , there was a further decline in FVC following radiation therapy . At the most recent follow-up evaluation , five of 29 patients ( 18 % ) who received ABVD alone and nine of 30 ( 30 % ) who received ABVD and RT reported persistent mild pulmonary symptoms ( P = .36 ) , which did not significantly affect normal daily activity . CONCLUSION ABVD chemotherapy induced acute pulmonary toxicity that required bleomycin dose modification in a substantial number of patients . The addition of RT result ed in a further decrease in FVC ; however , this did not significantly affect the functional status of patients This study aim ed at evaluating the role of consolidation radiation in a setting of Hodgkin 's lymphoma ( HL ) patients , using event-free survival ( EFS ) as end point . Among 260 patients treated with induction chemotherapy for bulky HL , 160 patients achieved negative residual masses at 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography ( FDG-PET ) scans .  They were r and omly divided into two well-matched groups to receive either 32 Gy radiotherapy to bulky area or no further therapy . At a median follow-up of 40 months , histology showed a malignancy in 14 % of patients in the chemotherapy-only group ( HL , 11 patients ) and in 4 % of patients in the chemotherapy + radiotherapy group ( HL , 2 patients ; carcinoma in previously irradiated area , 1 patient ) ( P = 0.03 ) . All the relapses in the chemotherapy-only group involved the bulky site and the contiguous nodal regions . Thus , the overall diagnostic accuracy of FDG-PET to exclude future relapses in the patients nonprotected by radiotherapy was 86 % with a false-negative rate of 14 % . Our study suggests that the addition of irradiation helps improve EFS in HL patients with post-chemotherapy FDG-PET-negative residual masses We performed a r and omized clinical trial to assess the usefulness and toxicity of combined therapy compared with chemotherapy and radiotherapy in the treatment of early stage Hodgkin 's disease with bulky disease as an adverse prognostic factor . Three-hundred and seven patients were enrolled into the study . They were r and omized to receive either radiotherapy ( extended field , generally mantle , 3500 cGy ) , or chemotherapy ( adriamycin , bleomicin , vinblastine and dacarbazine : ABVD , 6 monthly ) cycles or combined therapy ( three cycles of ABVD , followed by irradiation therapy and three more cycles of chemotherapy ) . The median follow-up duration from start of treatment was 11.4 years . Complete response rates were similar in the three arms : 83 % for radiotherapy ( 95 % confidence interval [ CI ] 67 - 92 % ) , 80 % for chemotherapy ( CI 69 - 88 % ) and 87 % for combined therapy ( CI 74 - 94 % ) . However , disease-free survival and overall survival were better in the patients treated with combined therapy . At 12 years 76 % ( CI 51 - 93 % ) of the patients treated with combined therapy remained alive in the first complete remission compared with 42 % ( CI 26 - 61 % ) in patients treated with radiotherapy and 48 % ( CI 31 - 57 % ) in patients who had received chemotherapy alone ( P < 0.01 ) . Improvement in overall survival was also evident at 12 years : 88 % ( CI 59 - 93 % ) in those who had received combined therapy , compared with 53 % ( CI 36 - 67 % ) in the radiotherapy arm and 59 % ( CI 35 - 67 % ) in the chemotherapy group . Acute toxicity was more frequent in patients treated with combined therapy , but no death related treatment was observed in the three groups . Late toxicity was similar in the three treatment groups . Combined therapy with extended field radiotherapy and six cycles of chemotherapy is an effective treatment of patients with early stage bulky Hodgkin 's disease compared with chemotherapy or radiotherapy alone A total of 277 patients with untreated Hodgkin 's disease , clinical stages I-II , were r and omized to cyclophosphamide , vinblastine , procarbazine , and prednisone ( CVPP ) alone for 6 monthly cycles or to CVPP plus radiation therapy ( RT ) , 3,000 rad , to involved areas ( CVPP plus RT ) . One or more of the following factors were considered as unfavorable prognosis : age greater than 45 years , more than two lymph node areas involved , or bulky disease . In the favorable group , disease-free survival ( 77 % vs. 70 % ) or overall survival ( 92 % vs. 91 % ) at 84 months for CVPP versus RT plus CVPP was similar . Patients with unfavorable prognosis treated with RT plus CVPP had longer disease-free survival ( 75 % vs. 34 % ) ( P = .001 ) and overall survival ( 84 % vs. 66 % ) than patients treated with CVPP alone Today it is possible to cure more than 90 % of children and adolescents with Hodgkin 's disease with a combination of radiotherapy and chemotherapy . Since the DAL-HD 82 study , the main scientific focus has been on avoiding late effects such as the OPSI syndrome , late complications involving the heart , lungs , thyroid and /or gonads particularly sterility in men and premature onset of menopause in women , and the prevention of secondary malignancies . The GPOH-HD 2003 study will introduce FDG-PET to the initial diagnostic program and the assessment of response to therapy in order to evaluate further possibilities for reducing therapy . In this context , the central review of all clinical and radiological findings , systematic ally done since the DAL-HD 90 study , will be increasingly relevant in maintaining st and ardised stage classification and therapy group assignment which was established by the preceding studies . Continuing in the direction of the earlier studies , the indications for radiotherapy will be restricted even further . In the early stages ( treatment group 1 ) patients with CR or a negative FDG-PET at the end of chemotherapy will receive no radiotherapy in order to reduce the risk of a secondary malignancy . In a r and omized comparison , procarbazine will be replaced by dacarbazine in the COPP cycles to determine whether sterility in men and premature onset of menopause in women can be avoided by elimination of procarbazine while retaining the same clinical efficacy . Finally , relapse therapy is to be tailored according to the time of relapse , the initial therapy group , and the patient 's response to the relapse therapy with more patients receiving autologous transplantation in order to further improve the results of relapse treatment PURPOSE To investigate whether radiotherapy can be reduced without loss of efficacy from extended field ( EF ) to involved field ( IF ) after four cycles of chemotherapy . PATIENTS AND METHODS Between 1993 and 1998 , patients with newly diagnosed early-stage unfavorable HD were enrolled onto this multicenter study . Patients were r and omly assigned to receive cyclophosphamide , vincristine , procarbazine , and prednisone ( COPP ) + doxorubicin , bleomycin , vinblastine , and dacarbazine ( ABVD ) for two cycles followed by radiotherapy of 30 Gy EF + 10 Gy to bulky disease ( arm A ) or 30 Gy IF + 10 Gy to bulky disease ( arm B ) . RESULTS Of 1,204 patients r and omly assigned to treatment , 1,064 patients were informative and eligible for the arm comparison ( 532 patients in arm A ; 532 patients in arm B ) . The median observation time was 54 months . Five years after r and om assignment , the overall survival ( OSran ) for all eligible patients was 91 % and freedom from treatment failure ( FFTFran ) was 83 % . Survival rates at 5 years after start of radiotherapy revealed no differences for arms A and B , respectively , in terms of FFTF ( 85.8 % and 84.2 % ) and OS at 5 years ( 90.8 % and 92.4 % ) . There also were no differences between arms A and B , respectively , in terms of complete remission ( 98.5 % and 97.2 % ) , progressive disease ( 0.8 % and 1.9 % ) , relapse ( 6.4 % and 7.7 % ) , death ( 8.1 % and 6.4 % ) , and secondary neoplasia ( 4.5 % and 2.8 % ) . In contrast , acute side effects including leukopenia , thrombocytopenia , nausea , gastrointestinal toxicity , and pharyngeal toxicity were more frequent in the EF arm . CONCLUSION Radiotherapy volume size reduction from EF to IF after COPP + ABVD chemotherapy for two cycles produces similar results and less toxicity in patients with early-stage unfavorable HD PURPOSE We report results of a r and omized trial comparing ABVD ( doxorubicin , bleomycin , vinblastine , and dacarbazine ) chemotherapy alone with treatment that includes radiation therapy in patients with limited-stage Hodgkin 's lymphoma . PATIENTS AND METHODS Patients with nonbulky clinical stage I to IIA Hodgkin 's lymphoma were stratified into favorable and unfavorable risk cohorts . Patients allocated to radiation-containing therapy received subtotal nodal radiation if favorable risk or combined-modality therapy if unfavorable risk . Patients allocated to ABVD received four to six treatment cycles . RESULTS We evaluated 399 patients . Median follow-up is 4.2 years . In comparison with ABVD alone , 5-year freedom from disease progression is superior in patients allocated to radiation therapy ( P = .006 ; 93 % v 87 % ) ; no differences in event-free survival ( P = .06 ; 88 % v 86 % ) or overall survival ( P = .4 ; 94 % v 96 % ) were detected . In a subset analyses comparing patients stratified into the unfavorable cohort , freedom from disease progression was superior in patients allocated to combined-modality treatment ( P = .004 ; 95 % v 88 % ) ; no difference in overall survival was detected ( P = .3 ; 92 % v 95 % ) . Of 15 deaths observed , nine were attributed to causes other than Hodgkin 's lymphoma or acute treatment-related toxicity . CONCLUSION In patients with limited-stage Hodgkin 's lymphoma , no difference in overall survival was detected between patients r and omly assigned to receive treatment that includes radiation therapy or ABVD alone . Although 5-year freedom from disease progression was superior in patients receiving radiation therapy , this advantage is offset by deaths due to causes other than progressive Hodgkin 's lymphoma or acute treatment-related toxicity To determine if 6 courses of chemotherapy alone could achieve the same or better outcome than 4 courses of chemotherapy followed by radiation therapy ( chemoradiotherapy ) in pediatric and adolescent patients with Hodgkin disease . Children ≤21 years old with biopsy-proven , pathologically staged I , IIA , or IIIA1 Hodgkin disease were r and omly assigned 6 courses of alternating nitrogen mustard , oncovin , prednisone , and procarbazine/doxorubicin , bleomycin , vinblastine , and dacarbazine ( treatment 1 ) or 4 courses of alternating nitrogen mustard , oncovin , prednisone , and procarbazine/doxorubicin , bleomycin , vinblastine , and dacarbazine + 2550 cGy involved-field radiotherapy ( treatment 2 ) . The complete response rate was 89 % , with a complete response and partial response rate of 99.4 % . There was no statistically significant difference in event-free survival ( EFS ) or overall survival between arms . The EFS for those who achieved an early complete response was significantly higher than for those who did not . For pediatric patients with asymptomatic low-stage and intermediate-stage Hodgkin disease  , chemotherapy and chemoradiotherapy both result ed in 3-year EFS of approximately 90 % and statistically indistinguishable 8-year EFS and overall survival , without significant long-term toxicity . Early response to therapy was associated with higher EFS , a concept that has led to the Children 's Oncology Group paradigm of response-based risk-adapted therapy for pediatric Hodgkin disease SINCE 1964 , all the efforts of the Lymphoma Group of the EORTC ( European Organisation for Research and Treatment of Cancer ) have been devoted to the task of tailoring treatment to the presentation of Hodgkin ’s disease ( HD ) for any given patient [ l-12 ] . We will first briefly review the results of the four controlled studies conducted by the group from 1964 to 1988 for stages I and II HD . We will then present in detail the design s of the on-going H7 r and omised trials for these same subsets of Hodgkin ’s disease patients PURPOSE Combined modality treatment using multidrug chemotherapy ( CTh ) and radiotherapy ( RT ) is currently considered the st and ard of care in early stage Hodgkin 's disease . Its role in advanced stages , however , continues to be debated . This study was aim ed at evaluating the role of consolidation radiation in patients achieving a complete remission after six cycles of doxorubicin , bleomycin , vinblastine , and dacarbazine ( ABVD ) chemotherapy  using event-free survival ( EFS ) and overall survival ( OS ) as primary end points . PATIENTS AND METHODS Two hundred and fifty-one patients with Hodgkin 's disease attending the lymphoma clinic at the Tata Memorial Hospital ( Mumbai , India ) from 1993 to 1996 received induction chemotherapy with six cycles of ABVD after initial staging evaluation . A total of 179 of 251 patients ( 71 % ) achieved a complete remission after six cycles of ABVD chemotherapy and constituted the r and omized population . Patients were r and omly assigned to receive either consolidation radiation or no further therapy . RESULTS With a median follow-up of 63 months , the 8-year EFS and OS in the CTh-alone arm were 76 % and 89 % , respectively , as compared with 88 % and 100 % in the CTh+RT arm ( P = .01 ; P = .002 ) . Addition of RT improved EFS and OS in patients with age < 15 years ( P = .02 ; P = .04 ) , B symptoms ( P = .03 ; P = .006 ) , advanced stage ( P = .03 ; P = .006 ) , and bulky disease ( P = .04 ; P = .19 ) . CONCLUSION Our study suggests that the addition of consolidation radiation helps improve the EFS and OS in patients achieving a complete remission after six cycles of ABVD chemotherapy , particularly in the younger age group and in patients with B symptoms and bulky and advanced disease PURPOSE To evaluate in a r and omized trial the impact of three versus six cycles of cyclophosphamide , vinblastine , procarbazine , and prednisone ( CVPP ) chemotherapy in favorable-prognosis and  CVPP versus doxorubicin , vincristine , prednisone , and etoposide ( AOPE ) plus involved-field radiotherapy ( RT ) in intermediate-prognosis previously untreated Hodgkin 's disease . PATIENTS AND METHODS Of 256 patients evaluated , 80 with a favorable prognosis according to a prognostic index design ed by the Grupo Argentina de Tratamiento de Leucemia Aguda ( GATLA ) were r and omized to three versus six cycles of CVPP without RT and 176 with intermediate risk to CVPP versus AOPE  , both for six cycles with RT between the third and fourth cycles of 30 Gy to the involved areas at diagnosis . CVPP consisted of intravenous ( I.V. ) cyclophosphamide and vinblastine on days 1 and 8 , and oral procarbazine and prednisone on days 1 to 14 , every 28 days . AOPE consisted of I.V. doxorubicin and vincristine on day 1 , oral prednisone on days 1 to 5 , and I.V. etoposide on days 1 and 3 , every 28 days . RESULTS Complete remission was obtained in 39 of 41 ( 95 % ) patients treated with three cycles of CVPP and 36 of 39 ( 92 % ) treated with six cycles in the favorable-risk group ( difference not significant [ NS ] ) . In the intermediate-risk group , 89 of 92 ( 97 % ) treated with CVPP plus RT versus 75 of 84 ( 89 % ) treated with AOPE plus RT achieved a complete remission ( P = .05 ) . At 60 months , the event-free survival ( EFS ) and overall survival rates in the favorable-risk group were 80 % and 91 % for CVPP x 3 and 84 % and 97 % for CVPP x 6 , respectively ( P = NS ) . In the intermediate-risk group , 60-month EFS rate for CVPP plus RT was 85 % , compared with 66 % for AOPE plus RT ( P = .009 ) . The overall survival rate was 95 % versus 87 % respectively ( P = .157 ) . CONCLUSION Three cycles of CVPP without RT are equally effective as six cycles in the favorable-risk group . However , in the intermediate-group , CVPP plus RT is superior to AOPE plus RT , with significantly fewer events before and after induction ( P = .009 ) , without a difference in overall survival To minimize the drawbacks of treatment we had shown in a previous study that it was possible after chemotherapy to limit the radiation fields to the involved areas only . Pursuing our policy of deescalation , we started in January 1982 a study in 29 French pediatric and hematologic centers , with two aims : ( 1 ) To compare the efficacy of 4 cycles of two different chemotherapeutic regimens ( 4 ABVD vs 2 MOPP + ABVD ) in early stages ( CSIA and II A ) while other stages would receive 6 cycles of the same regimen ( 3 MOPP + 3 ABVD ) ; ( 2 ) To evaluate the efficacy of irradiation given at a low dose ( 20 Gy ) in the patients who had a minimum 70 % reduction of the size of their nodes ( good responders ) . From January 1982 to March 1987 , 174 patients were entered in this study , of whom 157 completed their treatment program at the time of analysis . On completion of chemotherapy , 94 % were considered as good responders and were irradiated to 20 Gy . Only 6 patients received a mediastinal boost ( up to 40 Gy ) . Of the 6 % ( 10/157 ) poor responders a complete remission was obtained in 6 after 40 Gy . Among the good responders , 5 patients relapsed , with only 3 within an area irradiated to 20 Gy . So that 4 nodal relapses occurred among 364 involved lymph areas . The actuarial survival at 42 months ( median 30 months ) is 95 % ( IA + IIA = 100 % , IB + IIB + III = 94 % and IV = 80 % ) and the disease-free survival 88 % ( respectively 94 , 93 and 54 ) . Until now there is no statistically significant difference between the 2 r and omized arms . This study shows that it is possible to achieve a durable remission in most children treated with a less toxic protocol eliminating or reducing Nitrogen Mustard and reducing the dose of irradiation . Less late complications and sequelae are expected with a longer follow-up BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline .  Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias
BACKGROUND Combined modality treatment ( CMT ) consisting of chemotherapy followed by localised radiotherapy is st and ard treatment for patients with early stage Hodgkin lymphoma ( HL ) .
However , due to long term adverse effects such as secondary malignancies , the role of radiotherapy has been question ed recently and some clinical study groups advocate chemotherapy only for this indication .
OBJECTIVES We performed a systematic review with meta- analysis of r and omised controlled trials ( RCTs ) comparing chemotherapy alone with CMT in patients with early stage Hodgkin lymphoma with respect to response rate , progression-free survival ( alternatively tumour control ) and overall survival ( OS ) .