Kobe 2018.

Study characteristics
Methods	Secondary citation(s) Borchmann 2017 Language of publication English Study design Open‐label, international, randomised phase 3 trial Study centre(s) 301 hospitals and private practices in five European countries Countries Germany, Switzerland, Austria, the Netherlands, Czech Republic Median follow‐up time (range) Not reported for entire study population
Participants	Number of included participants Total: 2101 Qualified for randomisation: 1945 Inclusion criteria Histologically proven primary diagnosis of HL Advanced stages: stage IIB with one or both of the risk factors large mediastinal mass and extranodal lesions, or stage III or IV No previous treatment for HL Age 18‐60 years at inclusion Normal organ function, except for HL‐related impairments Negative HIV test Negative pregnancy test Life expectancy > 3 months Exclusion criteria Incomplete diagnosis of the disease stage Prior or concurrent disease that prevents treatment according to protocol HL as part of a composite lymphoma Prior chemotherapy or radiation Malignant disease within the last 5 years (exceptions: basalioma, carcinoma in situ of the cervix uteri, completely resected melanoma TNMpT1) Pregnancy, lactation Eastern Cooperative Oncology Group (ECOG) performance status > 2 Long‐term ingestion of corticosteroids or antineoplastic drugs Patient's lack of accountability, inability to appreciate the nature, meaning and consequences of the trial and to formulate his/her own wishes correspondingly Noncompliance: refusal of blood products during treatment, epilepsy, drug dependency, change of residence to abroad, prior cerebral injury or similar circumstances that appear to make protocol treatment or long‐term follow‐up impossible Antiepileptic treatment General intolerance of any protocol medication Unsafe contraceptive methods Relationship of dependence or employer‐employee relationship to the sponsor or the investigator Commitment to an institution on judicial or official order Participation in another interventional trial that could interact with this trial Consent Yes; written, including consent to participate in the trial and to storage of data and tissue samples Recruitment period 14 May, 2008 to 18 July 2014 Age (range, in years) Not reported for entire study population (Borchmann 2017) Ethnic group(s) Not reported Stages of disease Advanced stages: stage III‐IV, or stage II with B symptoms and one or both risk factors of large mediastinal mass Comorbidities None, due to exclusion criteria Therapy regimen 6 or 8 cycles of eBEACOPP (standard arm) 4 cycles of eBEACOPP or 8 cycles of eBEACOPP with rituximab (experimental arm)
Prognostic factor(s)	Prognostic factor(s) Interim PET Definition of prognostic factor(s) Not reported Timing of prognostic factor measurement Between day 17 and day 21 of cycle 2 of chemotherapy Method for measurement (use of specific scale and cut‐off) Deauville 5‐point scoring system PET negative defined as scores 1 or 2, PET positive defined as scores 3 to 5 A multidisciplinary panel of experts centrally interpreted all scans Was the same definition and method for measurement used in all participants? Yes Were prognostic factor(s) assessed blinded for outcome(s), and for each other (if relevant)? No; assessors who were masked to local findings, centrally reviewed PET‐2 and CT scans as well as x‐rays and clinical information (Borchmann 2017)
Outcome(s)	Primary outcome(s) and definition(s) Progression‐free survival (PFS), defined as the time from completion of staging until progression, relapse, or death from any cause Secondary outcome(s) and definition(s) Overall survival (OS), defined as time from completion of staging until death from any cause Timing of outcome measurement At 3 years Was the same definition and method for measurement used in all participants? Yes Was/were outcome(s) assessed blinded for prognostic factor(s), and for each other (if relevant)? Not reported
Missing data	Participants with any missing value? Participants with progressive disease, denoted by DS5 (Deauville score 5), were taken off protocol 505 participants treated before the protocol amendment in June 2011 were excluded from survival analysis If yes, how were missing data handled? Participants with missing data were excluded from analysis
Analysis	Univariable analysis: Yes Total number of participants included in univariable analysis for each outcome OS: 722 PFS: 722 Statistical method Kaplan‐Meier (survival analysis) Cox regression analysis (hazard ratios) How was the prognostic factor treated? Binary Multivariable analysis: Yes Total number of participants included in multivariable analysis for each outcome OS: 722 PFS: 722 Statistical method Kaplan‐Meier (survival analysis) Cox regression analysis (hazard ratios) How was the prognostic factor treated? Binary Number of candidate covariates 9 List of all candidate covariates Clinical stage B symptoms Large mediastinal mass Extra‐nodal involvement Involvement of 3 or more nodal areas Elevated erythrocyte sedimentation rate International Prognosis Score HL subtype PET positivity (DS4 vs. 1‐3)
Risk of bias (QUIPS)	Study participation Low risk Clear description of participants and study characteristics. Study attrition Low risk Length of follow‐up reported. Exclusion of participants due to safety amendment during the study. Prognostic factor measurement Low risk Adequate measurement and description. Outcome: Overall survival Outcome measurement Low risk Clear definition. Outcome measured the same way for all participants. 'Other prognostic factors (covariates)' Low risk Only advanced stages included. Statistical analysis and reporting Low risk Statistical method appropriate for the data. Outcome: Progression‐free survival Outcome measurement Low risk Clear definition. Outcome measured the same way for all participants. 'Other prognostic factors (covariates)' Low risk Only advanced stages included. Statistical analysis and reporting Low risk Statistical method appropriate for the data. Outcome: Adverse events Not reported
Notes	Conflict of interest We declare no competing interests. Funding The HD18 trial was funded by the Deutsche Krebshilfe (No. 107957 and 110617) and the Swiss State Secretariat for Education, Research and Innovation (SERI), and supported by Roche Pharma AG (No. ML‐21683).