Pediatric Leukemia/Lymphoma Patients Have Worse Patient-Reported Health Status Than Pediatric Solid Tumor and CNS Tumor Patients during Intensive Treatment

Introduction: Children receiving treatment for cancer experience impaired health status. Health status during treatment can be systematically quantified using patient-reported outcome measures (PROs). PROs are any report of a patient's health status that comes directly from the patient and provide composite scores from a series of questions around a central concept to quantify the level of distress or impairment caused by a patient's symptoms, disease, or treatment. Previous work in pediatric leukemia patients and brain tumor patients measuring PROs over time demonstrated no change in patient-reported health status late in therapy compared to the end of therapy. Changes in patient function over the early, intensive phases of treatment have not been studied. Additionally, the impact of cancer disease type (Leukemia/Lymphoma, CNS Tumor, Solid Tumor) on patient-reported health status during intensive cancer therapy is not known.

The objective of this study was to characterize the impact of disease type on patient function related to mobility, fatigue, pain, anxiety, depression, and peer relationships over the initial six months of therapy. We hypothesized that CNS/Solid Tumor patients have worse self-reported health status than Leukemia/Lymphoma patients and that patient function worsened over time for all domains measured.

Methods: We conducted a prospective cohort study of children ages 5-21 yearsold with a new diagnosis of cancer. Patients were enrolled in the study for six months or until their treatment completed, whichever time period was shorter. Our primary outcome was patient function as measured using the Patient-Reported Outcome Measurement Information System (PROMIS) for impaired mobility, pain, fatigue, anxiety, depressive symptoms, and peer relationships. PROMIS is a validated PRO that provides separate scores for each domain measured (reported as T score) with a mean score of 50. Self-report participant assessments were obtained twice monthly on electronic tablets, at the beginning of a treatment cycle and approximately 1 week later. Intensity of therapy was determined using the Intensity of Treatment Rating (ITR-3) scale and classified as moderate, very, and most intensive treatments.

Patient demographics were analyzed using simple statistics. Analysis of changes in patient function used a generalized linear mixed model (GLMM) using predictors of type of cancer and time from diagnosis.

Results: Forty patients completed the study and had a mean age of 11.7 years (SD 4.7). Fifty-eight percent of the patients were male and 60% of patients had Leukemia/Lymphoma. Forty percent of patients received moderate intensity treatment, 47.5% received very intensive, and 12.5% received most intensive treatment. The intensity of treatments was similar in the Leukemia/Lymphoma group and the CNS/Solid Tumor group (p=0.21).

Disease Group: CNS/Solid Tumor patients have better self-reported health status for all domains measured compared to Leukemia/Lymphoma patients. CNS/Solid Tumor patients report better mobility (higher T scores) compared to Leukemia/Lymphoma patients by a factor of 1.1 (p<0.001), less fatigue (lower T scores) by a factor of 0.83 (p<0.001), less pain (lower T scores) by a factor of 0.83 (p<0.001), less anxiety (lower T scores) by a factor of 0.83 (p<0.001), less depressive symptoms (lower T scores) by a factor of 0.85 (p<0.001), and better peer relationships (higher T scores) by a factor of 1.11 (p=0.0036).

Time from diagnosis: Time from diagnosis has a significant effect on patient-report of pain for both Leukemia/Lymphoma and CNS/Solid Tumor patients, with improved pain over time. At 100 days from diagnosis, pain scores decrease by a factor of 0.91 (p=0.008). Time from diagnosis did not have a significant effect on patient function in any other domain measured.

Conclusion: Leukemia/Lymphoma patients experience significantly worse patient functioning compared to patients with CNS/Solid Tumors over the first six months of cancer treatment.In addition, as time from diagnosis increases patient function related to pain improves. The significant burden of disease for Leukemia/Lymphoma patients demonstrated in this study is a surprising finding and perhaps reflects an underestimation of the burden of Leukemia/Lymphoma treatment because of the overall favorable prognosis for most of the children with these diagnoses.