For the or i ginal version of this review, we searched MEDLINE, Embase and CENTRAL as well as conference proceedings (American Society of Hematology, American Society of Clinical Oncology and International Symposium of
Hodgkin Lymphoma) from January 1980 to November 2010 for randomised controlled trials (RCTs) comparing
chemotherapy alone versus
chemotherapy regimens plus
radiotherapy. For the updated review we searched MEDLINE, CENTRAL and conference proceedings to December 2016.
SELECTION CRITERIA: We included RCTs comparing
chemotherapy alone with
chemotherapy plus
radiotherapy in patients with early stage HL. We excluded trials with more than 20% of patients in advanced stage. As the value of
radiotherapy in addition to
chemotherapy is still not clear, we also compared to more cycles of
chemotherapy in the control arm. In this updated review, we also included a second comparison evaluating trials with varying numbers of cycles of
chemotherapy between intervention and control arms, same
chemotherapy regimen in both arms assumed. We excluded trials evaluating children only, therefore only trials involving adults are included in this updated review.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of trials. We contacted study authors to obtain missing information. As effect measures we used hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RR) for response rates. Since not all trials reported PFS according to our definitions, we evaluated all similar outcomes (e.g. event-free survival) as PFS/tumour control.
MAIN RESULTS: Our search led to 5518 potentially relevant references. From these, we included seven RCTs in the analyses involving 2564 patients. In contrast to the first version of this review including five trials, we excluded trials randomising children. As a result, we excluded one trial from the former analyses and we identified three new trials.Five trials with 1388 patients compared the combination of
chemotherapy alone and
chemotherapy plus
radiotherapy, with the same number of
chemotherapy cycles in both arms. The addition of
radiotherapy to
chemotherapy has probably little or no difference on OS (HR 0.48; 95% confidence interval (CI) 0.22 to 1.06; P = 0.07, moderate- quality evidence), however two included trials had potential other high risk of bias due to a high number of patients not receiving planned
radiotherapy. After excluding these trials in a sensitivity analysis, the results showed that the combination of
chemotherapy and
radiotherapy improved OS compared to
chemotherapy alone (HR 0.31; 95% CI 0.19 to 0.52; P <0.00001, moderate- quality evidence). In contrast to
chemotherapy alone the use of
chemotherapy and
radiotherapy improved PFS (HR 0.42; 95% CI 0.25 to 0.72; P = 0.001; moderate- quality evidence). Regarding
infection- related mortality (RR 0.33; 95% CI 0.01 to 8.06; P = 0.5; low- quality evidence),
second cancer- related mortality (RR 0.53; 95% CI 0.07 to 4.29; P = 0.55; low- quality evidence) and
cardiac disease- related mortality (RR 2.94; 95% CI 0.31 to 27.55; P = 0.35;low- quality evidence), there is no evidence for a difference between the use of
chemotherapy alone and
chemotherapy plus
radiotherapy. For complete response rate (CRR) (RR 1.08; 95% CI 0.93 to 1.25; P = 0.33; low- quality evidence), there is also no evidence for a difference between treatment groups.Two trials with 1176 patients compared the combination of
chemotherapy alone and
chemotherapy plus
radiotherapy, with different numbers of
chemotherapy cycles in both arms. OS is reported in one trial only, the use of
chemotherapy alone (more
chemotherapy cycles) may improve OS compared to
chemotherapy plus
radiotherapy (HR 2.12; 95% CI 1.03 to 4.37; P = 0.04; low- quality evidence). This trial also had a potential other high risk of bias due to a high number of patients not receiving planned
therapy. There is no evidence for a difference between
chemotherapy alone and
chemotherapy plus
radiotherapy regarding PFS (HR 0.42; 95% CI 0.14 to 1.24; P = 0.12; low- quality evidence). After excluding the trial with patients not receiving the planned
therapy in a sensitivity analysis, the results showed that the combination of
chemotherapy and
radiotherapy improved PFS compared to
chemotherapy alone (HR 0.24; 95% CI 0.070 to 0.88; P = 0.03, based on one trial). For
infection- related mortality (RR 6.90; 95% CI 0.36 to 132.34; P = 0.2; low- quality evidence),
second cancer- related mortality (RR 2.22; 95% CI 0.7 to 7.03; P = 0.18; low- quality evidence) and
cardiac disease-related mortality (RR 0.99; 95% CI 0.14 to 6.90; P = 0.99; low-quality evidence), there is no evidence for a difference between the use of
chemotherapy alone and
chemotherapy plus
radiotherapy. CRR rate was not reported.
AUTHORS' CONCLUSIONS: This systematic review compared the effects of
chemotherapy alone and
chemotherapy plus
radiotherapy in adults with early stage HL .For the comparison with same numbers of
chemotherapy cycles in both arms, we found moderate- quality evidence that PFS is superior in patients receiving
chemotherapy plus
radiotherapy than in those receiving
chemotherapy alone. The addition of
radiotherapy to
chemotherapy has probably little or no difference on OS . The sensitivity analysis without the trials with potential other high risk of bias showed that
chemotherapy plus
radiotherapy improves OS compared to
chemotherapy alone.For the comparison with different numbers of
chemotherapy cycles between the arms there are no implications for OS and PFS possible, because of the low quality of evidence of the results.