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. 2024 Dec 2;12(12):CD007110.
doi: 10.1002/14651858.CD007110.pub4.

Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early-stage Hodgkin's lymphoma

Marius Goldkuhle  1 , Nina Kreuzberger  1 , Bastian von Tresckow  2   3 , Dennis A Eichenauer  2 , Lena Specht  4 , Ina Monsef  1 , Nicole Skoetz  1
Affiliations

Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early-stage Hodgkin's lymphoma

Marius Goldkuhle et al. Cochrane Database Syst Rev. .

Abstract

Background: Early-stage Hodgkin's lymphoma in adults is commonly treated with combined modality treatment of chemotherapy followed by radiotherapy. The role of radiotherapy has been questioned due to potential long-term adverse effects.

Objectives: To assess the effects of chemotherapy compared to chemotherapy plus radiotherapy in adults with early-stage Hodgkin's lymphoma.

Search methods: We updated all previous searches for randomised controlled trials (RCTs) on the databases Cochrane Central Register of Controlled Trial, MEDLINE and Embase, in trial registries and in relevant conference proceedings until November 2023.

Selection criteria: We included RCTs comparing chemotherapy alone with chemotherapy plus radiotherapy in adults with early-stage Hodgkin's lymphoma and excluded trials with more than 20% of participants with advanced Hodgkin's lymphoma. We considered immunotherapy in addition to chemotherapy eligible if both were applied similarly in the comparator groups, but did not identify such trials. For our comparisons, we separated RCTs with the same number of chemotherapy cycles in both arms and RCTs with a different number of cycles, when the chemotherapy regimens were the same. We separated RCTs which compared participants with a favourable, mixed or unfavourable risk profile.

Data collection and analysis: Two review authors independently screened search results, extracted data and assessed the quality of included trials. A third review author resolved discrepancies. We analysed time-to-event outcomes (overall survival, progression-free survival) as hazard ratios (HR) and binary outcomes (adverse events) as risk ratios (RR). We assessed the certainty of evidence using the GRADE approach.

Main results: We included nine comparisons of eight RCTs involving 3840 participants in this updated review. Same number of chemotherapy cycles in both trial arms Favourable disease For overall survival in individuals with favourable Hodgkin's lymphoma, the evidence is uncertain and inconclusive (HR 0.92, 95% confidence interval (CI) 0.11 to 7.92; 2 RCTs, 1245 participants; very low-certainty evidence due to study limitations, inconsistency and imprecision). Additional radiotherapy to chemotherapy is likely to improve progression-free survival (HR 0.36, 95% CI 0.20 to 0.68; 2 RCTs, 1245 participants; moderate-certainty evidence due to study limitations). The evidence was uncertain and inconclusive for second-cancer-related mortality (RR 0.93, 95% CI 0.01 to 74.24; 2 RCTs, 1245 participants; very low-certainty evidence due to study limitations, inconsistency and substantial imprecision) and suggests little to no difference in cardiac disease-related mortality (RR 0.89, 95% CI 0.06 to 14.16; 1 RCT, 667 participants; low-certainty evidence due to substantial imprecision). There were no data on infection-related mortality or infertility. Mixed population For a population of mixed risk profile, the evidence on overall survival is uncertain and inconclusive (HR 0.79, 95% CI 0.13 to 4.80; 2 RCTs, 572 participants; very low-certainty evidence due to study limitations, inconsistency and imprecision). It indicates that additional radiotherapy may lead to an improvement in progression-free survival (HR 0.71, 95% CI 0.43 to 1.17; 2 RCTs, 572 participants; low-certainty evidence due to study limitations and imprecision). The evidence is uncertain and inconclusive for infection-related mortality (RR 1.35, 95% CI 0.17 to 10.87; 2 RCTs, 572 participants) and second-cancer-related mortality (RR 0.52, 95% CI 0.09 to 2.98; 2 RCTs, 572 participants) (both very low-certainty evidence due to study limitations and substantial imprecision), but suggests that additional radiotherapy may increase cardiac disease-related mortality (RR 3.03, 95% CI 0.12 to 73.92; 1 RCT, 420 participants; low-certainty evidence due to substantial imprecision). There were no data on infertility. Unfavourable disease For individuals with unfavourable disease, the evidence on overall survival is uncertain and inconclusive (HR 0.69, 95% CI 0.20 to 2.44; 2 RCTs, 688 participants; very low-certainty evidence due to study limitations and substantial imprecision), but additional radiotherapy probably improves progression-free survival (HR 0.55, 95% CI 0.19 to 1.60; 1 RCT, 651 participants; moderate-certainty evidence due to imprecision). The evidence was uncertain and inconclusive for cardiac disease-related mortality (RR 2.85, 95% CI 0.12 to 65.74; 1 RCT, 37 participants; very low-certainty evidence due to study limitations and substantial imprecision). There were no data on infection-related mortality, second-cancer related mortality or infertility. Different number of chemotherapy cycles in both trial arms Favourable disease The evidence for overall survival in individuals with favourable disease treated with different numbers of chemotherapy cycles in both arms is uncertain and inclusive (HR 0.36, 95% CI 0.04 to 3.38; 1 RCT, 357 participants; very low-certainty evidence due to study limitations and substantial imprecision), yet it suggests a likely improvement in progression-free survival with additional radiotherapy (HR 0.08, 95% CI 0.02 to 0.32; 1 RCT, 357 participants; moderate-certainty evidence due to study limitations). For second-cancer-related mortality, the evidence is uncertain and inconclusive (RR 0.21, 95% CI 0.01 to 4.34; 1 RCT, 465 participants; very low-certainty evidence due to study limitations and substantial imprecision). There were no data on infection-related mortality and infertility and data for cardiac disease-related mortality were not estimable (no events in either group). Unfavourable disease For individuals with an unfavourable risk profile, additional radiotherapy may decrease overall survival slightly (HR 1.66, 95% CI 0.95 to 2.90; 2 RCTs, 698 participants; low-certainty evidence due to study limitations and imprecision), but may slightly improve progression-free survival (HR 0.84, 95% CI 0.53 to 1.33; 2 RCTs, 698 participants; low-certainty evidence due to study limitations and imprecision). The evidence is uncertain and inconclusive for infection-related mortality (RR 6.90, 95% CI 0.36 to 132.34; 1 RCT, 276 participants), second-cancer-related mortality (RR 2.19, 95% CI 0.77 to 6.19; 2 RCTs, 870 participants) and cardiac disease-related mortality (RR 1.60, 95% CI 0.31 to 8.22; 2 RCTs, 870 participants) (all very low-certainty evidence due to study limitations and substantial imprecision). There were no data on infertility.

Authors' conclusions: The chemotherapy regimens in the trials differed and data for regimens commonly used today were limited. Additional radiotherapy may slightly improve progression-free survival. The available data for overall survival and adverse events were of low and very low certainty, and we were unable to draw conclusions about the effects of additional radiotherapy on these outcomes. No studies evaluated infertility. High-quality, longer-term follow-up data are required and data on fertility are needed.

Trial registration: ClinicalTrials.gov NCT02292979 NCT01868451.

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Conflict of interest statement

MG: member of the editorial group of Cochrane Haematology (Editor), but was not involved in the editorial process for this review. No other known conflict of interest.

NK: member of the editorial group of Cochrane Haematology (Editor), but was not involved in the editorial process for this review. No other known conflict of interest.

BvT: declares grant/research funding from Esteve, Merck Sharp & Dohme Corporation, Novartis and Takeda Pharmaceutical Company (all paid to institution). He also declares 1. consulting fees from Allogene, Amgen, Bristol‐Myers Squibb, Cerus Corporation, Gilead Sciences Inc, Incyte Corporation, IQVIA Ltd, Lilly Deutschland, Merck Sharp and Dohme, Miltenyi Biotec, Noscendo GmbH, Novartis Pharma, PentixaPharm GmbH, Pfizer Canada Inc, Pierre Fabre Pharmaceuticals, Inc, Qualworld, Quintiles Transnational Corp, Roche, Sobi, Inc and Takeda Pharmaceutical Company; 2. honoraria for speaking engagements from AbbVie, AstraZeneca, Bristol‐Myers Squibb, Gilead Sciences Inc, Incyte Corporation, Lilly Deutschland, Merck Sharp and Dohme, Novartis, Roche and Takeda Pharmaceutical Company; and 3. travel support from AbbVie, AstraZeneca, Gilead Sciences Inc, Lilly Deutschland, Merck Sharp and Dohme, Novartis, Pierre Fabre Pharmaceuticals, Inc, Roche and Takeda Pharmaceutical Company (all personal payments). BvT is a health professional in haematology and stem cell transplantation at University Hospital Essen and an Editor with Cochrane Haematology. He was not involved in the editorial process for this review. BvT was engaged with studies included in this systematic review (HD16; HD17). Therefore, he was not involved in eligibility decisions, data extraction, risk of bias assessment and GRADE assessments involving these studies.

DAE: honoraria from TAKEDA and Sanofi‐Genzyme.

LS: conflicts of interest: Advisory Board member: Takeda, Kyowa Kirin; Royalties: Springer Verlag, Munksgaard Publishing; research grants: Varian, ViewRay, Danish Cancer Society; employers: Rigshospitalet, Department of Oncology, Capital Region, Denmark; University of Copenhagen, Faculty of Health and Medical Sciences, Denmark; leadership: Vice‐Chairman, International Lymphoma Radiation Oncology Group (ILORG); Board Member, Chairman of Radiotherapy Committee, Danish Lymphoma Group. LS is an Editor with Cochrane Haematology. She was not involved in the editorial process of this review. LS was engaged with the H10F/H10U study included in this review. Therefore, she was not involved in eligibility decisions, data extraction, risk of bias assessment and GRADE assessments involving this study.

IM: member of the editorial group of Cochrane Haematology (Information Specialist), but was not involved in the editorial process for this review. No other known conflict of interest.

NS: member of the editorial group of Cochrane Haematology (Editor) and head of the Germany‐Cochrane Evidence Synthesis Unit, but was not involved in the editorial process for this review. No other known conflict of interest.

Figures

1
1
PRISMA flow diagram.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1: Overall survival – same number of chemotherapy cycles – early favourable disease only, Outcome 1: All trials
1.2
1.2. Analysis
Comparison 1: Overall survival – same number of chemotherapy cycles – early favourable disease only, Outcome 2: Subgroup analysis – no interim PET vs interim PET‐negative individuals only
1.3
1.3. Analysis
Comparison 1: Overall survival – same number of chemotherapy cycles – early favourable disease only, Outcome 3: Subgroup analysis – ABVD chemotherapy vs EBVP chemotherapy
2.1
2.1. Analysis
Comparison 2: Progression‐free survival – same number of chemotherapy cycles – early favourable disease only, Outcome 1: All trials
2.2
2.2. Analysis
Comparison 2: Progression‐free survival – same number of chemotherapy cycles – early favourable disease only, Outcome 2: Subgroup analysis – no interim PET vs interim PET‐negative individuals only
2.3
2.3. Analysis
Comparison 2: Progression‐free survival – same number of chemotherapy cycles – early favourable disease only, Outcome 3: Subgroup analysis – ABVD chemotherapy vs EBVP chemotherapy
3.1
3.1. Analysis
Comparison 3: Adverse events‐related mortality – same number of chemotherapy cycles – early favourable disease only, Outcome 1: Second‐cancer‐related mortality
3.2
3.2. Analysis
Comparison 3: Adverse events‐related mortality – same number of chemotherapy cycles – early favourable disease only, Outcome 2: Cardiac disease‐related mortality
4.1
4.1. Analysis
Comparison 4: Overall survival – same number of chemotherapy cycles – mixed population, Outcome 1: All trials
4.2
4.2. Analysis
Comparison 4: Overall survival – same number of chemotherapy cycles – mixed population, Outcome 2: Subgroup analysis – no interim PET vs interim PET‐negative individuals only
4.3
4.3. Analysis
Comparison 4: Overall survival – same number of chemotherapy cycles – mixed population, Outcome 3: Subgroup analysis – involved field radiotherapy vs mixed radiotherapy
5.1
5.1. Analysis
Comparison 5: Progression‐free survival – same number of chemotherapy cycles – mixed population, Outcome 1: All trials
5.2
5.2. Analysis
Comparison 5: Progression‐free survival – same number of chemotherapy cycles – mixed population, Outcome 2: Subgroup analysis – no interim PET vs interim PET‐negative individuals only
5.3
5.3. Analysis
Comparison 5: Progression‐free survival – same number of chemotherapy cycles – mixed population, Outcome 3: Subgroup analysis – involved field radiotherapy vs mixed radiotherapy
6.1
6.1. Analysis
Comparison 6: Adverse events‐related mortality – same number of chemotherapy cycles – mixed population, Outcome 1: Infection‐related mortality
6.2
6.2. Analysis
Comparison 6: Adverse events‐related mortality – same number of chemotherapy cycles – mixed population, Outcome 2: Second‐cancer‐related mortality
6.3
6.3. Analysis
Comparison 6: Adverse events‐related mortality – same number of chemotherapy cycles – mixed population, Outcome 3: Cardiac disease‐related mortality
7.1
7.1. Analysis
Comparison 7: Overall survival – same number of chemotherapy cycles – early unfavourable disease only, Outcome 1: All trials
7.2
7.2. Analysis
Comparison 7: Overall survival – same number of chemotherapy cycles – early unfavourable disease only, Outcome 2: Subgroup analysis – no interim PET vs interim PET‐negative individuals only
7.3
7.3. Analysis
Comparison 7: Overall survival – same number of chemotherapy cycles – early unfavourable disease only, Outcome 3: Subgroup analysis – radiotherapy after chemotherapy vs chemotherapy after radiotherapy
7.4
7.4. Analysis
Comparison 7: Overall survival – same number of chemotherapy cycles – early unfavourable disease only, Outcome 4: Subgroup analysis – CVPP chemotherapy vs eBEACOPP and ABVD chemotherapy
8.1
8.1. Analysis
Comparison 8: Progression‐free survival – same number of chemotherapy cycles – early unfavourable disease only, Outcome 1: All trials
9.1
9.1. Analysis
Comparison 9: Adverse events‐related mortality – same number of chemotherapy cycles – early unfavourable disease only, Outcome 1: Cardiac disease‐related mortality
10.1
10.1. Analysis
Comparison 10: Overall survival – different numbers of chemotherapy cycles – early favourable disease only, Outcome 1: All trials
11.1
11.1. Analysis
Comparison 11: Progression‐free survival – different numbers of chemotherapy cycles – early favourable disease only, Outcome 1: All trials
12.1
12.1. Analysis
Comparison 12: Adverse events related mortality – different numbers of chemotherapy cycles – early favourable disease only, Outcome 1: Second‐cancer‐related mortality
12.2
12.2. Analysis
Comparison 12: Adverse events related mortality – different numbers of chemotherapy cycles – early favourable disease only, Outcome 2: Cardiac disease‐related mortality
13.1
13.1. Analysis
Comparison 13: Overall survival – different numbers of chemotherapy cycles – early unfavourable disease only, Outcome 1: All trials
13.2
13.2. Analysis
Comparison 13: Overall survival – different numbers of chemotherapy cycles – early unfavourable disease only, Outcome 2: Subgroup analysis – no interim PET vs interim PET‐negative individuals only
13.3
13.3. Analysis
Comparison 13: Overall survival – different numbers of chemotherapy cycles – early unfavourable disease only, Outcome 3: Subgroup analysis – bulky disease vs non‐bulky disease
14.1
14.1. Analysis
Comparison 14: Progression‐free survival – different numbers of chemotherapy cycles – early unfavourable disease only, Outcome 1: All trials
14.2
14.2. Analysis
Comparison 14: Progression‐free survival – different numbers of chemotherapy cycles – early unfavourable disease only, Outcome 2: Subgroup analysis – no interim PET vs interim PET‐negative individuals only
14.3
14.3. Analysis
Comparison 14: Progression‐free survival – different numbers of chemotherapy cycles – early unfavourable disease only, Outcome 3: Subgroup analysis – bulky disease vs non‐bulky disease
15.1
15.1. Analysis
Comparison 15: Adverse events‐related mortality – different numbers of chemotherapy cycles – early unfavourable disease only, Outcome 1: Infection‐related mortality
15.2
15.2. Analysis
Comparison 15: Adverse events‐related mortality – different numbers of chemotherapy cycles – early unfavourable disease only, Outcome 2: Second‐cancer‐related mortality
15.3
15.3. Analysis
Comparison 15: Adverse events‐related mortality – different numbers of chemotherapy cycles – early unfavourable disease only, Outcome 3: Cardiac disease‐related mortality
See this image and copyright information in PMC

Update of

References

References to studies included in this review

CALGB 7751 {published data only}
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EORTC‐GELA H9‐F {published data only}
    1. Eghbali H, Brice P, Creemers GY, Kooji MM, Carde P, Van't Veer MB, et al. Comparison of three radiation dose levels after EBVP regimen in favourable supradiaphragmatic clinical stages (CS) I-II Hodgkin's lymphoma (HL): preliminary results of EORTC-GELA H9-F trial. Blood 2005;106(11 Suppl):abstract 814.
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    1. Thomas J, Fermé C, Noordijk EM, Eghbali H, Henry-Amar M. The EORTC-GELA treatment strategy in clinical stages I–II HL: results of the H9-F and H9-U trials. In: International Symposium on Hodgkin Lymphoma, Cologne, Presentation. 2007.
    1. Thomas J, Fermé C, Noordijk EM, Morschhauser F, Girinsky T, Gaillard I, et al. Comparison of 36 Gy, 20 Gy, or no radiation therapy after 6 cycles of EBVP chemotherapy and complete remission in early-stage Hodgkin lymphoma without risk factors: results of the EORTC-GELA H9-F intergroup randomized trial. International Journal of Radiation Oncology, Biology, Physics 2018;100(5):1133-45. - PubMed
H10F {published data only}
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    1. Aurer I, Neven A, Fiaccadori V, Counsell N, Phillips E, Clifton-Hadley L, et al. Relapses in interim PET negative limited stage Hodgkin lymphoma patients receiving ABVD with or without radiotherapy-analysis of EORTC/FIL/LYSA H10 and UK NCRI Rapid trials. Hematological Oncology 2021;39(Suppl 2):119-20. [DOI: 10.1002/hon.2879] - DOI
    1. Cottereau AS, Versari A, Loft A, Casasnovas O, Bellei M, Ricci R, et al. Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial. Blood 2018;131(13):1456-63. - PubMed
H10U {published data only}
    1. Andre MP, Girinsky T, Federico M, Reman O, Fortpied C, Gotti M, et al. Early positron emission tomography response-adapted treatment in stage I and II Hodgkin lymphoma: final results of the randomized EORTC/LYSA/FIL H10 trial. Journal of Clinical Oncology 2017;35(16):1786-96. - PubMed
    1. Andre MP, Reman O, Federico M, Girinski T, Brice P, Brusamolino E, et al. Interim analysis of the randomized EORTC/LYSA/FIl intergroup H10 trial on early PET-scan driven treatment adaptation in stage I/II Hodgkin lymphoma. Blood 2012;120:549.
    1. Andre MP. An update on the EORTC / LYSA / FIL H10 trial. In: 9th International Symposium on Hodgkin Lymphoma; 2013 Oct 12-15; Cologne, Germany. 2013.
    1. Aurer I, Neven A, Fiaccadori V, Counsell N, Phillips E, Clifton-Hadley L, et al. Relapses in interim PET negative limited stage Hodgkin lymphoma patients receiving ABVD with or without radiotherapy-analysis of EORTC/FIL/LYSA H10 and UK NCRI Rapid trials. Hematological Oncology 2021;39(Suppl 2):119-20. [DOI: 10.1002/hon.2879] - DOI
    1. Cottereau AS, Versari A, Loft A, Casasnovas O, Bellei M, Ricci R, et al. Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial. Blood 2018;131(13):1456-63. - PubMed
HD16 {published data only (unpublished sought but not used)}
    1. Baues C, Goergen H, Fuchs M, Kobe C, Dietlein M, Rosenbrock J, et al. Consolidating involved field radiotherapy prevents early and local recurrences in early stage Hodgkin lymphoma. International Journal of Radiation Oncology Biology Physics 2019;105(1):32-3.
    1. Baues C, Goergen H, Fuchs M, Rosenbrock J, Celik E, Eich H, et al. Involved-field radiation therapy prevents recurrences in the early stages of Hodgkin lymphoma in PET-negative patients after ABVD chemotherapy: relapse analysis of GHSG phase 3 HD16 trial. International Journal of Radiation Oncology, Biology, Physics 2021;111(4):900-6. [DOI: 10.1016/j.ijrobp.2021.07.1697] - DOI - PubMed
    1. Eich HT, Baues C, Fuchs M, Kobe C, Greil R, Sasse S, et al. PET-guided treatment of early-stage favorable Hodgkin lymphoma: final results of the international, randomized phase 3 trial HD16 by the GHSG. International Journal of Radiation Oncology, Biology, Physics 2019;105(1):1.
    1. Eichenauer DA, Buhnen I, Baues C, Kobe C, Kaul H, Greil R, et al. Interim PET-guided treatment for early-stage NLPHL: a subgroup analysis of the randomized GHSG HD16 and HD17 studies. Blood 2023;142(6):553-60. [DOI: 10.1182/blood.2023019939] - DOI - PubMed
    1. Eichenauer DA, Buhnen I, Fuchs M, Greil R, Moccia A, Zijlstra JM, et al. Interim PET-guided treatment of early-stage nodular lymphocyte-predominant Hodgkin lymphoma: a subgroup analysis of the GHSG HD16 and HD17 studies. Hemasphere 2022;6:10.
HD17 {published and unpublished data}
    1. Borchmann P, Kobe C, Plutschow A, Greil R, Meissner J, Topp MS, et al. Positron emission tomography guided omission of radiotherapy in early-stage unfavorable Hodgkin lymphoma: final results of the international, randomized Phase III HD17 trial by the German Hodgkin Study Group. Oncology Research and Treatment 2020;43:32. [DOI: 10.1159/000510995] - DOI
    1. Borchmann P, Kobe C, Plutschow A, Greil R, Meissner J, Topp MS, et al. Positron emission tomography guided omission of radiotherapy in early-stage unfavorable Hodgkin lymphoma: final results of the international, randomized Phase III HD17 trial by the German Hodgkin Study Group. Oncology Research and Treatment 2020;43:32. [DOI: 10.1159/000510995] - DOI
    1. Eichenauer DA, Buhnen I, Baues C, Kobe C, Kaul H, Greil R, et al. Interim PET-guided treatment for early-stage NLPHL: a subgroup analysis of the randomized GHSG HD16 and HD17 studies. Blood 2023;142(6):553-60. [DOI: 10.1182/blood.2023019939] - DOI - PubMed
    1. Eichenauer DA, Buhnen I, Fuchs M, Greil R, Moccia A, Zijlstra JM, et al. Interim PET-guided treatment of early-stage nodular lymphocyte-predominant Hodgkin Lymphoma: a subgroup analysis of the GHSG HD16 and HD17 studies. Hemasphere 2022;6:10.
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HD6 {published data only}
    1. Meyer R, Gospodarowicz M, Connors J, Pearcey R, Bezjak A, Wells W. A randomized phase III comparison of single-modality ABVD with a strategy that includes radiation therapy in patients with early-stage Hodgkin's disease: the HD-6 trial of the National Cancer Institute of Canada Clinical Trials Group (Eastern Cooperative Oncology Group Trial HD06). Blood 2003;11(11):26a. - PubMed
    1. Meyer RM, Gospodarowicz M, Connors JM, Pearcey RG, Wells WA, Winter JN. Final analysis of a randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy (RT) in patients with limited-stage Hodgkin lymphoma (HL): NCIC CTG/ECOG HD.6. Blood 2011;118:21. - PubMed
    1. Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Bezjak A, Wells WA, et al. 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. Journal of Clinical Oncology 2005;23(21):4634-42. - PubMed
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MSKCC trial #90‐44 {published data only}
    1. Straus DJ, Portlock CS, Qin J, Myers J, Zelenetz AD, Moskowitz C, et al. 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 non-bulky Hodgkin disease. Blood 2004;104(12):3483-9. - PubMed
UK NCRI Rapid {published data only}
    1. Adams HJ, Kwee TC. RAPID trial demonstrates low positive predictive value of interim FDG-PET in early-stage Hodgkin lymphoma after three cycles of ABVD. Journal of Pediatric Hematology/Oncology 2016;38(2):165. [DOI: 10.1097/MPH.0000000000000483] - DOI - PubMed
    1. Aurer I, Neven A, Fiaccadori V, Counsell N, Phillips E, Clifton-Hadley L, et al. Relapses in interim PET negative limited stage Hodgkin lymphoma patients receiving ABVD with or without radiotherapy-analysis of EORTC/FIL/LYSA H10 and UK NCRI rapid trials. Hematological Oncology 2021;39(Suppl 2):119-20. [DOI: 10.1002/hon.2879] - DOI
    1. Barrington S, Phillips EH, Counsell N, Hancock B, Pettengell R, Johnson P, et al. Treatment escalation in patients with early stage Hodgkin lymphoma and a positive PET scan after initial chemotherapy is not always required: subsidiary analysis of the UK NCRI Rapid study. British Journal of Haematology 2018;181:24.
    1. Barrington SF, Phillips EH, Counsell N, Hancock B, Pettengell R, Johnson P, et al. Positron emission tomography score has greater prognostic significance than pretreatment risk stratification in early-stage Hodgkin lymphoma in the UK RAPID Study. Journal of Clinical Oncology 2019;37(20):1732-41. - PMC - PubMed
    1. Cutter DJ, Ramroth J, Diez P, Buckle A, Ntentas G, Popova B, et al. Predicted risks of cardiovascular disease following chemotherapy and radiotherapy in the UK NCRI RAPID Trial of positron emission tomography-directed therapy for early-stage Hodgkin lymphoma. Journal of Clinical Oncology 2021;39(32):3591-601. [DOI: 10.1200/JCO.21.00408] - DOI - PMC - PubMed

References to studies excluded from this review

Andrieu 1999 {published data only}
    1. Andrieu JM, Jais JP, Escoffre-Barbe M, Delwail V, Desablens B, Kiladjian JJ, et al. Bulky Hodgkin's disease (B-HD): treatment with an initial 7 drug chemotherapy (CT) delivered over 12 weeks followed by high dose extended field irradiation (EF-RT). Seven year results of the GOELAMS H90M multicentric randomized trial. Blood 1999;94(10 Suppl):abstract 528a.
Anonymous 2014 {published data only}
    1. Anonymous. Final analysis of a randomized phase II study with prednisone, vinblastine, doxorubicin, and gemcitabine in patients with early unfavorable Hodgkin lymphoma-PVAG-14 Pilot. Clinical Advances in Hematology and Oncology 2014;12(8 Suppl 16):14-5. - PubMed
Bloomfield 1988 {published data only}
    1. Bloomfield CD, Pajak TF, Glicksman AS, Gottlieb AJ, Coleman M, Nissen NI, et al. Chemotherapy and combined modality therapy for Hodgkin's disease: a progress report on Cancer and Leukemia Group B studies. Cancer Treatment Reports 1982;66(4):835-46. - PubMed
Bonnet 2007 {published data only}
    1. Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, et al. 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. Journal of Clinical Oncology 2007;25(7):787-92. - PubMed
BREACH {published and unpublished data}
    1. Fornecker LM, Lazarovici J, Aurer I, Casasnovas RO, Gac AC, Bonnet C, et al. Brentuximab Vedotin plus AVD for first-line treatment of early-stage unfavorable Hodgkin lymphoma (BREACH): a multicenter, open-label, randomized, phase II trial. Journal of Clinical Oncology 2023;41(2):327-35. [DOI: 10.1200/JCO.21.01281] - DOI - PubMed
Brusamolino 1994 {published data only}
    1. Brusamolino E, Lazzarino M, Orlandi E, Canevari A, Morra E, Castelli G, et al. Early-stage Hodgkin's disease: long-term results with radiotherapy alone or combined radiotherapy and chemotherapy. Annals of Oncology 1994;5(Suppl 2):101-6. - PubMed
Burnelli 2018 {published data only}
    1. Burnelli R, Rinieri S, Rondelli R, Todesco A, Bianchi M, Garaventa A, et al. Long-term results of the AIEOP MH'96 childhood Hodgkin's lymphoma trial and focus on significance of response to chemotherapy and its implication in low risk patients to avoid radiotherapy. Leukemia and Lymphoma 2018;59(11):2612-21. - PubMed
CALGB 50801 {published data only}
    1. LaCasce AS, Dockter T, Ruppert AS, Kostakoglu L, Schoder H, Hsi E, et al. Positron emission tomography-adapted therapy in bulky stage I/II classic Hodgkin lymphoma: CALGB 50801 (Alliance). Journal of Clinical Oncology 2023;41(5):1023-34. [DOI: 10.1200/JCO.22.00947] - DOI - PMC - PubMed
Cheveresan 1998 {published data only}
    1. Cheveresan LF, Roth I, Balan M, Ionita H. Combined modality therapy in early stage Hodgkin's disease – preliminary results of a clinical trial. Leukemia and Lymphoma 1998;29(Suppl 1):72.
Cimino 1990 {published data only}
    1. Cimino G. Chemotherapy alone for the treatment of early-stage Hodgkin's disease. European Journal of Cancer 1990;26(11-12):1115-8. - PubMed
Cosset 1992 {published data only}
    1. Cosset JM, Henry-Amar M, Meerwaldt JH, Carde P, Noordijk EM, Thomas J, et al. The EORTC trials for limited stage Hodgkin's disease. European Journal of Cancer 1992;28A(11):1847-50. - PubMed
Dann 2017 {published data only}
    1. Dann EJ, Bairey O, Bar-Shalom R, Mashiach T, Barzilai E, Kornberg A, et al. Modification of initial therapy in early and advanced Hodgkin lymphoma, based on interim PET/CT is beneficial: a prospective multicentre trial of 355 patients. British Journal of Haematology 2017;178(5):709-18. - PubMed
Desablens 1999 {published data only}
    1. Desablens B, Jais JP, Lacotter-Thierry L, Foussard C, Escoffre-Barbe M, Moreau P, et al. Treatment of CS IA to IIIB non-bulky Hodgkin's disease (NB-HD) with 3 cycles of chemotherapy (CT) (ABVD vs EBVM) followed by high dose irradiation (RT). Results of the GOELAMS H90-NM multicentre randomized trial. Blood 1999;94(10 Suppl 1):abstract 386a.
Dionet 1988 {published data only}
    1. Dionet C, Oberlin O, Habrand JL, Vilcoq J, Madelain M, Dutou L, et al. 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. International Journal of Radiation Oncology, Biology, Physics 1988;15(2):341-6. - PubMed
Ferme 2005 {published data only}
    1. Ferme C, Diviné M, Vranovsky A, Morschhauser F, Bouabdallah R, Gabarre J, et al. Four ABVD and involved­ field radiotherapy in unfavorable supradiaphragmatic clinical stages (CS) I­II Hodgkin's lymphoma (HL): preliminary results of the EORTC­GELA H9­U trial. Blood 2005;106(11):abstract A-813.
Friedmann 2014 {published data only}
    1. Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, et al. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group study AHOD0031. Journal of Clinical Oncology 2014;32(32):3651-8. - PMC - PubMed
GATLA {published data only}
    1. Pavlovsky A, Fernandez I, Kurgansky N, Prates V, Zoppegno L, Negri P, et al. PET-adapted therapy after three cycles of ABVD for all stages of Hodgkin lymphoma: results of the GATLA LH-05 trial. British Journal of Haematology 2019;185(5):865-73. [DOI: 10.1111/bjh.15838] - DOI - PubMed
    1. Pavlovsky S, Corrado C, Pavlovsky MA, Prates MV, Zoppegno L, Giunta M, et al. Risk-adapted therapy with three or six cycles of oxorubicin/bleomycin/vinblastine/dacarbazine plus involved-field radiation therapy in Hodgkin lymphoma, based on prognosis at diagnosis and early response: results from the GATLA study. Clinical Lymphoma, Myeloma and Leukemia 2010;10(3):181-5. [DOI: 10.3816/CLML.2010.n.028] - DOI - PubMed
HD0607 {published data only}
    1. Biggi A, Chauvie S, Fallanca F, Guerra L, Bergesio F, Menga M, et al. Predictive value on advance Hodgkin lymphoma treatment outcome of end-of treatment FDG PET/CT in the HD0607 clinical trial. Hematological Oncology 2023;41(3):415-23. [DOI: 10.1002/hon.3117] - DOI - PubMed
    1. Gallamini A, Rambaldi A, Patti C, Romano A, Viviani S, Silvia B, et al. Lesion dissemination in baseline PET/CT (D-MAX) and IPS score predict ABVD treatment outcome in PET-2 negative advanced-stage Hodgkin lymphoma patients enrolled in the prospective GITIL/FIL HD0607 trial. Blood 2021;138:2443. [DOI: 10.1182/blood-2021-152292] - DOI
    1. Gallamini A, Rossi A, Patti C, Picardi M, Romano A, Cantonetti M, et al. Consolidation radiotherapy could be omitted in advanced Hodgkin lymphoma with large nodal mass in complete metabolic response after ABVD: final analysis of the randomized HD0607 trial. Hematological Oncology 2019;37:147-8. - PubMed
HD0801 {published data only}
    1. Fondazione Italiana Linfomi ONLUS. High-dose chemotherapy and stem cell transplantation, in patients PET-2 positive, after 2 courses of ABVD and comparison of RT versus no RT in PET-2 negative patients (HD0801). www.clinicaltrials.gov/study/NCT00784537 (first received 3 November 2008). [CLINICALTRIALS.GOV: NCT00784537]
    1. Ricardi U, Levis M, Evangelista A, Gioia DM, Sacchetti GM, Gotti M, et al. Role of radiotherapy to bulky sites of advanced Hodgkin lymphoma treated with ABVD: final results of FIL HD0801 trial. Blood Advances 2021;5(21):4504-14. [DOI: 10.1182/bloodadvances.2021005150] - DOI - PMC - PubMed
Hirsch 1994 {published data only}
    1. Hirsch A. The effect of ABVD chemotherapy with and without mediastinal irradiation on pulmonary function and symptoms in early-stage Hodgkin's disease. International Journal of Radiation Oncology, Biology, Physics 1994;30(Suppl 1):168.
Hirsch 1996 {published data only}
    1. Hirsch A, Vander EN, Straus DJ, Gomez EG, Leung D, Portlock CS, et al. Effect of ABVD chemotherapy with and without mantle or mediastinal irradiation on pulmonary function and symptoms in early-stage Hodgkin's disease. Journal of Clinical Oncology 1996;14(4):1297-305. - PubMed
Horning 1996 {published data only}
    1. Horning SJ, Bennett JM, Bartlett NL, Williams J, Neuberg D, Cassileth PA. 12 weeks of chemotherapy (STANFORD V) and involved field radiotherapy (RT) are highly effective for bulky and advanced stage Hodgkin's disease (HD): a limited institution ECOG pilot study. Blood 1996;88(10 Suppl (Pt 1)):673a.
Horning 2007 {published data only}
    1. Horning SJ, Hoppe RT, Advani RH, Breslin S, McCormick E, Allen J, et al. A prospective trial of involved field radiation (IFRT) + chemotherapy vs. extended field radiation (EFRT) for favorable Hodgkin's disease (HD): long-term follow-up and implications for current combined modality. Haematologica 2007;92(Suppl 5):53.
INDIE {published data only}
    1. Brockelmann PJ, Kaul H, Fuchs M, Kobe C, Baues C, Borchmann P, et al. Trial in progress: individualized immunotherapy in early-stage unfavourable Hodgkin lymphoma – the investigator-initiated phase II GHSG INDIE trial. Hemasphere 2022;6:29.
    1. University of Cologne. Phase II trial of individualized immunotherapy in early-stage unfavorable classical Hodgkin lymphoma. clinicaltrials.gov/study/NCT04837859 (first received 6 April 2021). [CLINICALTRIALS.GOV: NCT04837859]
KEYNOTE‐C11 {published data only}
    1. IncMerck Sharp & Dohme Corpa subsidiary of Merck & Co. Phase 2 study of pembrolizumab and chemotherapy in patients with newly diagnosed classical Hodgkin lymphoma (KEYNOTE-C11). clinicaltrials.gov/study/NCT05008224 (first received 13 August 2021). [CLINICALTRIALS.GOV: NCT05008224]
Kim 2003 {published data only}
    1. Kim HK, Silver B, Li S, Neuberg D, Mauch P. Hodgkin's disease in elderly patients (> or =60): clinical outcome and treatment strategies. International Journal of Radiation Oncology, Biology, Physics 2003;56(2):556-60. - PubMed
Kobe 2017 {published data only}
    1. Kobe C, Goergen H, Fuchs M, Eich HT, Baues C, Diehl V, et al. Treatment reduction in patients with advanced-stage Hodgkin lymphoma and negative interim FDG-PET: final results of the international, randomized, phase 3 HD18 trial by the German Hodgkin Study Group. European Journal of Nuclear Medicine and Molecular Imaging 2017;44(2):S312.
Körholz 2004 {published data only}
    1. Körholz D, Claviez A, Hasenclever D, Kluge R, Hirsch W, Kamprad F, et al. The concept of the GPOH-HD 2003 therapy study for pediatric Hodgkin's disease: evolution in the tradition of the DAL/GPOH studies. Klinische Pädiatrie 2004;216(3):150-6. - PubMed
Kumar 2021 {published data only}
    1. Kumar A, Casulo C, Advani RH, Budde E, Barr PM, Batlevi CL, et al. Brentuximab vedotin combined with chemotherapy in patients with newly diagnosed early-stage, unfavorable-risk Hodgkin lymphoma. Journal of Clinical Oncology 2021;39(20):2257-65. [DOI: 10.1200/JCO.21.00108] - DOI - PubMed
Kung 1993 {published data only}
    1. Kung FH, Behm FG, Cantor A, Falletta J, Ferree CR, Leventhal BG, et al. Abbreviated chemotherapy vs chemoradiotherapy in early stage Hodgkin's disease of childhood. Proceedings of the American Society of Clinical Oncology 1993;12:414.
Kung 2006 {published data only}
    1. Kung FH. POG 8625: a randomized trial comparing chemotherapy with chemoradiotherapy for children and adolescents with stages I, IIA, IIIA Hodgkin disease: a report from the children's oncology group. Journal of Pediatric Hematology/Oncology 2006;28(6):362-8. - PubMed
Laskar 2004 {published data only}
    1. Laskar S, Gupta T, Vimal S, Muckaden MA, Saikia TK, Pai SK, et al. Consolidation radiation after complete remission in Hodgkin's disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need? Journal of Clinical Oncology 2004;22(1):62-8. - PubMed
Lemerle 1986 {published data only}
    1. Lemerle J, Oberlin O, Schaison G, Leverger G, Olive D, Duffilot B. Effectiveness of primary chemotherapy and low-dose radiation (RT) in childhood Hodgkin's disease (HD) [abstract]. In: Proceedings of the American Society of Clinical Oncology. 1986.
Longo 1992 {published data only}
    1. Longo DL, DeVita VT. The use of combination chemotherapy in the treatment of early stage Hodgkin's disease. In: De Vita VT, Helman S, Rosenberg SA, editors(s). Important Advances in Oncology. Philadelphia (PA): Lippincott Williams & Wilkins, 1992:155-65. - PubMed
Meyer 2013 {published data only}
    1. Meyer RM. Radiation in early-stage Hodgkin lymphoma. Clinical Advances in Hematology & Oncology 2013;11(3):162-89. - PubMed
Nachman 2002 {published data only}
    1. Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, et al. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. Journal of Clinical Oncology 2002;20(18):3765-71. - PubMed
Noordijk 2006 {published data only}
    1. Noordijk EM, Carde P, Dupouy N, Hagenbeek A, Krol AD, Kluin-Nelemans JC, et al. 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. Journal of Clinical Oncology 2006;24(19):3128-35. - PubMed
O'Dwyer 1984 {published data only}
    1. O'Dwyer PJ, Stewart MB, Wiernik PH. MOPP vs radiotherapy/MOPP for early-stage Hodgkin's disease (HD) – a six year follow-up. 2nd International Conference on Malignant Lymphoma; 1984 Jun 13-16, 1984; Lugano, Switzerland.
O'Dwyer 1985 {published data only}
    1. O'Dwyer PJ, Wiernik PH, Stewart MB, Slawson RG. Treatment of early stage Hodgkin's disease: a randomized trial of radiotherapy plus chemotherapy versus chemotherapy alone. In: Cavilli F, Bonadonna G, Rozencweig M, editors(s). Malignant Lymphomas and Hodgkin's Disease: Experimental and Therapeutic Advances. Boston (MA): Maritinus Nijhoff, 1985:329-36.
Park 2017 {published data only}
    1. Park SI, Olajide O, Reddy NM, Budde LE, Ghosh N, Richards KL, et al. Brentuximab vedotin consolidation to reduce radiation use in patients with limited stage non-bulky Hodgkin lymphoma: an update from a phase 2 clinical trial. Hematological Oncology 2017;35:81-2.
Pavlovsky 1997 {published data only}
    1. Pavlovsky S, Schvartzman E, Lastiri F, Magnasco H, Corrado C, Raslawski E, et al. 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. Journal of Clinical Oncology 1997;15(7):2652-8. - PubMed
Picardi 2007 {published data only}
    1. Picardi M, De Renzo A, Pane F, Nicolai E, Pacelli R, Salvatore M, et al. Randomized comparison of consolidation radiation versus observation in bulky Hodgkin's lymphoma with post-chemotherapy negative positron emission tomography scans. Leukemia & Lymphoma 2007;48(9):1721-7. - PubMed
RADAR {published data only}
    1. Radford J, Adedayo T, Ardavan A, Barrington SF, Berkahn L, Chauvie S, et al. RADAR: an international phase III, PET response adapted, randomised trial in progress, comparing ABVD ± ISRT with brentuximab vedotin + AVD + ISRT in patients with previously untreated limited-stage classical Hodgkin lymphoma. Hemasphere 2022;6:12-3.
Radford 2002 {published data only}
    1. Radford JA, Cowan RA, Ryder WD, Johnson RJ, Bannerjee SS, Deakin DP, et al. Four weeks of VAPEC-B chemotherapy before involved field radiotherapy minimises the relapse rate in early stage low-risk Hodgkin's disease and is not associated with an excess of second malignancy. Annals of Oncology 2002;13(Suppl 2):25.
RAFTING {published data only}
    1. EUCTR2020-002382-33-PL. Radiation-Free therapy for the Initial treatment of Good prognosis early non-bulky HL, defined by a low Metabolic Tumor Volume and a negative interim PET after 2 chemotherapy cycles – RAFTING. www.clinicaltrialsregister.eu/ctr-search/search?query=EUCTR2020-002382-3... (first received 12 April 2021). [EUCTR: EUCTR2020-002382-33-PL]
    1. Gallamini A, Sudria A, Kurlapski M, Gastaud L. Revisiting the predictive role of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography on treatment outcome in early-stage favorable Hodgkin lymphoma. Hematological Oncology 2023;41(4):608-11. [DOI: 10.1002/hon.3158] - DOI - PubMed
    1. Medical University of Gdansk. Radiation free chemotherapy for early Hodgkin lymphoma (RAFTING). clinicaltrials.gov/study/NCT04866654 (first received 22 Apr 2021). [CLINICALTRIALS.GOV: NCT04866654]
Reinartz 2013 {published data only}
    1. Reinartz G, Eich HT. Does involved field radiotherapy improve survival for children with Hodgkin's lymphoma in complete remission after chemotherapy? Strahlentherapie und Onkologie 2013;189(4):344-6. - PubMed
Rüffer 1996 {published data only}
    1. Rüffer U, Brosteanu O, Sieber M, Koch T, Löffler M, Pfreundschuh M. Reduction of radiotherapy in early stage Hodgkin's disease: results of a randomized trial in patients PS I/II. Annals of Oncology 1996;7(Suppl 3):49.
Rüffer 1998 {published data only}
    1. Rüffer U, Sieber M, Pfistner B, Tesch H, Engert A, Bredenfeld H, et al. Reduction of radiotherapy volume in intermediate Hodgkin's disease: interim analysis of a randomized trial in patients CS I/II of the GHSG. Blood 1998;92(10 Suppl 1 (Pt 1)):abstract 626a.
Rüffer 1999 {published data only}
    1. Rüffer JU, Sieber M, Pfistner B, Tesch H, Engert A, Bredenfeld H, et al. For intermediate stage Hodgkin's disease extended field radiation after effective chemotherapy is obsolete: interim analysis of HD9 trial (GHSG). Blood 1999;94(10 Suppl 1):528a.
Sasse 2017 {published data only}
    1. Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, et al. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. Journal of Clinical Oncology 2017;35(18):1999-2007. - PubMed
Specht 1992 {published data only}
    1. Specht L, Carde P, Mauch P, Magrini SM, Santarelli MT. Radiotherapy versus combined modality in early stages. Annals of Oncology 1992;3(Suppl 4):77-81. - PubMed
Straus 1989 {published data only}
    1. Straus DJ, Myers J, Lee BJ, Koziner B, Nisce LZ, Redman J. Limited chemotherapy and radiation therapy (RT) for early clinical stage (CS) Hodgkin's disease (HD). High complete remission (CR) percentage, disease free survival (DFS) and low toxicity. Blood 1989;74(7 Suppl 1):239a.
Straus 2018 {published data only}
    1. Straus DJ, Jung SH, Pitcher B, Kostakoglu L, Grecula JC, Hsi ED, et al. CALGB 50604: risk-adapted treatment of non-bulky early-stage Hodgkin lymphoma based on interim PET. Blood 2018;132(10):1013-21. - PMC - PubMed
Thistlethwaite 2007 {published data only}
    1. Thistlethwaite F, Qian W, Williams MV, Hancock BW, Hoskin P, Sun-Mynt H, et al. Selection of patients for minimal initial chemotherapy (MIC); the impact of Hasenclever score on outcome in patients receiving MIC and involved field radiotherapy for clinical stage IA/IIA supra-diaphragmatic Hodgkin lymphoma in the UK NCRI LY07 trial. Haematologica 2007;92(Suppl 5):52.
Thomas 2004 {published data only}
    1. Thomas J, Ferme C, Noordijk EM, Rieux C, Divine M, Brice P, et al. Six cycles of ABVD + IF­RT vs. four cycles of ABVD + IF­RT vs. four cycles of BEACOPP + IF­RT in unfavourable supradiaphragmatic clinical stages I­II Hodgkin's lymphoma: the EORTC­GELA H9­U randomized clinical trial (20982) in 808 patients. European Journal of Haematology 2004;73(Suppl 65):40.
Weiner 1997 {published data only}
    1. Weiner MA, Leventhal B, Brecher ML, Marcus RB, Cantor A, Gieser PW, et al. Randomized study of intensive MOPP-ABVD with or without low-dose total-nodal radiation therapy in the treatment of stages IIB, IIIA2, IIIB, and IV Hodgkin's disease in pediatric patients: a Pediatric Oncology Group study. Journal of Clinical Oncology 1997;15(8):2769-79. - PubMed
Wolden 2012 {published data only}
    1. Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, et al. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma – a report from the Children's Oncology Group. Journal of Clinical Oncology 2012;30(26):3174-80. - PMC - PubMed
Zubizarreta 2017 {published data only}
    1. Zubizarreta PA, Alfaro E, Guitter M, Sanchez La Rosa C, Galluzzo ML, Millan N, et al. Children and adolescent Hodgkin lymphoma in Argentina: long-term results after combined ABVD and restricted radiotherapy. Journal of Pediatric Hematology/Oncology 2017;39(8):602-8. - PubMed

References to studies awaiting assessment

Mexico B2H031 {published data only}
    1. Aviles A, Delgado S. A prospective clinical trial comparing chemotherapy, radiotherapy and combined therapy in the treatment of early stage Hodgkin's disease with bulky disease. Clinical & Laboratory Haematology 1998;20(2):95-9. - PubMed

Additional references

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