The online version of this article has a supplementary appendix.Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication. We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were hazard ratios for OS and tumor control as well as relative risks for complete response (CR). Meta-analyses were performed using RevMan5. Five randomized controlled trials involving 1,245 patients were included. The hazard ratio (HR) was 0.41 (95% confidence interval (CI) 0.25 to 0.66) for tumor control and 0.40 (95% CI 0.27 to 0.59) for OS for patients receiving CMT compared to chemotherapy alone. CR rates were similar between treatment groups. In sensitivity analyses another 6 trials were included that did not fulfill the inclusion criteria of our protocol but were considered relevant to the topic. These trials underlined the results of the main analysis. In conclusion, adding radiotherapy to chemotherapy improves tumor control and OS in patients with early stage Hodgkin's lymphoma.Key words: combined modality treatment, chemotherapy, Hodgkin's lymphoma.Citation: Herbst C, Rehan FA, Brillant C, Bohlius J, Skoetz N, Schulz H, Monsef I, Specht L, and Engert A. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review. Haematologica. 2010.95:494-500. doi:10.3324/haematol.2009 This is an open-access paper. ABSTRACT therapy.The main objective of this systematic review was to compare chemotherapy alone with identical chemotherapy plus radiotherapy in patients with early stage HL with respect to overall survival, tumor control and complete response rates.

Adding radiotherapy to chemotherapy improves tumour control and overall survival in patients with early stage Hodgkin lymphoma.

Both chemotherapy (CT) alone and combined modality therapy (CMT) are effective modalities for the treatment of early stages of Hodgkin lymphoma (HL). However, the optimal choice of treatment is still being discussed. Different research groups reported that ABVD-like CT followed by radiotherapy is highly effective for early favourable and early unfavourable (intermediate) stage HL. A recently conducted randomized trial aimed at determining whether CMT is superior to CT alone in early stages, showed no significant difference in 5 year overall survival (OS) and event-free survival in patients treated with either 4–6 cycles of ABVD alone or 2 cycles of ABVD plus radiotherapy. Thus, this systematic review and meta-analysis was performed for a more comprehensive comparison. Methods: Only randomized controlled trials (RCT) comparing CT alone with CMT in newly diagnosed adults with early stages of HL (CS IA, IB, IIA, IIB) were included. Medline and Cochrane Library were systematically searched for randomized controlled trials from 1975 to 2007. Patients who received CMT were considered as experimental group and patients who received ABVD-like CT alone were considered as control group. Data were collected from full text publications or abstracts and treatment effects for OS were calculated as hazard ratios (HR). Results: A total of 590 references were screened. Four eligible RCTs were identified, including 1207 patients with early-stage HL (early favourable and early unfavourable stages). Between 1983 and 2004, 765 patients where treated with CMT and 442 patients with CT alone. The OS for the CMT group was significantly better than the OS for the CT-alone group (HR: 0.54; 95% CI [0.35 - 0.84]; p = 0.006), but there was evidence for a substantial heterogeneity between the studies (I2 = 69%, p=0.02). Discussion: First results of this systematic review showed improved OS for patients treated with CMT in early-stage HL compared to patients treated with CT alone. The substantial heterogeneity between the trials should be clarified. Further comprehensive analyses are ongoing and will provide more detailed information.

Background Combined modality treatment (CMT) consisting of chemotherapy followed by localised radiotherapy is standard 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 questioned recently and some clinical study groups advocate chemotherapy only for this indication. Objectives We performed a systematic review with meta-analysis of randomised 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). Search strategy We searched MEDLINE, EMBASE and CENTRAL as well as conference proceedings from January 1980 to November 2010 for randomised controlled trials comparing chemotherapy alone to the same chemotherapy regimen plus radiotherapy. Selection criteria Randomised controlled trials comparing chemotherapy alone with CMT in patients with early stage HL. Trials in which the chemotherapy differed between treatment arms were excluded. Trials with more than 20% of patients in advanced stage were also excluded. Data collection and analysis Effect measures used were hazard ratios (HR) for tumour control and OS as well as relative risks for response rates. Two review authors independently extracted data and assessed quality of trials. We contacted study authors to obtain missing information. Since none of the trials reported progression-free survival according to our definitions, all similar outcomes were evaluated as tumour control. 1 Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma (Review)