Background: Patients undergoing cancer treatment experience global stress and cancer-specific stress. Both types of stress are associated with a higher symptom burden.

Objective: In this cross-sectional study, we used a comprehensive set of demographic, clinical, and symptom characteristics to evaluate their relative contribution to the severity of global and cancer-specific stress.

Methods: Patients (N = 941) completed study questionnaires before their second or third cycle of chemotherapy.

Results: Consistent with our a priori hypothesis, we found both common and distinct characteristics associated with higher levels of global stress and cancer-specific stress. A significant proportion of our patients had scores on the Impact of Event Scale-Revised suggestive of subsyndromal (29.4%) or probable (13.9%) posttraumatic stress disorder. Four of the 5 stepwise linear regression analyses for the various stress scales explained between 41.6% and 54.5% of the total variance. Compared with various demographic and clinical characteristics, many of the common symptoms associated with cancer and its treatments uniquely explained a higher percentage of the variance in the various stress scales. Symptoms of depression made the largest unique contribution to the percentage of total explained variance across all 5 scales.

Conclusion: Clinicians need to assess for global stress, cancer-specific stress, and depression in patients receiving chemotherapy.

Implications for practice: Patients may benefit from integrative interventions (eg, mindfulness-based stress reduction, cognitive behavioral therapy, acupuncture) that simultaneously address stress and symptoms commonly associated with cancer and its treatments.