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Purpose: Relief of symptoms is critical for supportive care in medical oncology.This NCI funded study compared usual care to an educational and systems change intervention in a Comprehensive Cancer Center.Based on the NCCN Pain and Fatigue guidelines, interventions included a four part patient education program, professional education and strategies to integrate symptom management into routine oncology practice comparing the total N=184 patients including Breast (40%), Lung (25%), Colon (20%) or Prostate (15%) cancer.Methods: This trial compared symptom management in outpatient oncology patients experiencing pain and/or fatigue who received either usual care (N=83) or the intervention (N=101).Outcome measures included Pain and Fatigue Knowledge Scales, Psychological Distress Thermometer, City of Hope QOL Tool, Kamofsky Scale and Piper Fatigue Scale.Patients were assessed at baseline and 1 and 3 months post intervention endpoints.Results: To determine the immediate effect of the intervention and differences from the usual care condition, 2×2 repeated measures ANOVAs were conducted on instrument scales and single item measures.Compared to the usual care sample, the intervention had an immediate salutary effect on anxiety, depression, and social support (p=.007, p=.006, and p=.048, respectively).Barriers to pain management decreased significantly only for the intervention sample.Knowledge of pain decreased in the usual care sample but increased significantly in the intervention sample (p<.001).Fatigue decreased significantly in the intervention sample (p=.006 to p<.001) and often increased in the usual care sample.Knowledge of fatigue also increased significantly for the intervention sample (p<.001), while falling in the usual care sample.Conclusions: Structured patient and professional education and systems change efforts can reduce barriers to pain and fatigue management resulting in improved outcomes for patients in treatment for solid tumors.