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Background . Osteosarcoma is a highly malignant bone tumour. After the second relapse, the 12-month postrelapse disease-free survival (PRDFS) rate decreases below 20%. Oral Etoposide is often used in clinical practice after surgery as an “adjuvant” outside any protocol and with only limited evidence of improved survival.  Viscum album fermentatum Pini  ( Viscum ) is an extract of mistletoe plants grown on pine trees for subcutaneous (sc) injection with immunomodulatory activity.  Methods . Encouraged by preliminary findings, we conducted a study where osteosarcoma patients free from disease after second metastatic relapse were randomly assigned to  Viscum  sc or Oral Etoposide. Our goal was to compare 12-month PRDFS rates with an equivalent historical control group.  Results . Twenty patients have been enrolled, with a median age of 34 years (range 11–65) and a median follow-up time of 38.5 months (3–73). The median PRDSF is currently 4 months (1–47) in the Etoposide and 39 months (2–73) in the  Viscum  group. Patients getting  Viscum  reported a higher quality of life due to lower toxicity.  Conclusion .  Viscum  shows promise as adjuvant treatment in prolonging PRDFS after second relapse in osteosarcoma patients. A larger study is required to conclusively determine efficacy and immunomodulatory mechanisms of  Viscum  therapy in osteosarcoma patients.

A Randomized Study on Postrelapse Disease-Free Survival with Adjuvant Mistletoe versus Oral Etoposide in Osteosarcoma Patients