The Prognostic Value for Survival of Patient-Reported Outcomes in Hematological Malignancies: A Systematic Review
Authors: Campinha-Bacote Avrita , Trask Peter C , Efficace Fabio 
Published: October 2019

Abstract
Introduction: Patient-reported outcomes (PROs) are now critical to more comprehensively evaluate treatment outcomes in oncology. There is convincing evidence indicating that, similarly to traditional biomarkers, PROs may also predict survival outcomes. This systematic review examined state of the art literature on the prognostic value of PROs for survival in hematological malignancies.
Methods: We searched PubMed and Google Scholar from 2000-2016 for studies assessing the predictive relationship between PROs and overall survival (OS) in Acute Myelogenous Leukemia (AML), Chronic Lymphocytic Lymphoma (CLL), Diffuse Large B-Cell Lymphoma (DLBCL), indolent Non-Hodgkin's Lymphoma (iNHL), Follicular Lymphoma (FL), marginal Zone Lymphoma (mZL), Myelodysplastic Syndrome (MDS), and Multiple Myeloma (MM). Search terms included but were not limited to: quality of life, physical functioning, predictive/prognostic, survival, patient-reported outcomes, and fatigue. Studies were excluded if they did not use multivariate analyses, did not examine OS as an endpoint, were case reports, did not report results for PROs, were reported in an abstract only, or used only clinician-reported outcomes as a predictor. A pre-defined data extraction form (DEF) was used to assess the following data from each article: disease, sample size, demographics, type of PRO measures included, clinical parameters included as predictors, type of analysis, and outcomes assessed.
Results: 223 articles were reviewed of which 13 met the inclusion criteria (6 AML/MDS, 3 MM, 2 aggressive lymphomas, 1 mixed heme diagnoses, and 1 DLBCL). PROs in these studies were captured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core30 (EORTC QLQ-C30) or the EORTC myeloma module 24 item (MY24), a health-related quality of life questionnaire for patients with myelodysplastic syndromes (QOL-E), Functional Assessment of Cancer Treatment (FACT) or Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and the MD Anderson Symptom Inventory (MDASI). PROs that were independently associated with OS in multivariate analyses from the different studies were: physical function, fatigue, pain, difficulty with strenuous activity, and impaired physical performance in AML patients; physical function and fatigue in MM; fatigue in MDS; global/total QOL and functional well-being in aggressive lymphomas; drowsiness in a mixed group of heme diagnoses; and global QOL, function, and symptoms/signs in DLBCL (see Table). Baseline PROs were obtained following diagnosis of de novo or relapsed disease in 3 studies, within 6 months of registration in 1 study, and prior to any treatment in 6 studies.
Conclusions: PROs related to physical functioning, fatigue, and performance were the most common predictors of OS in hematological malignancies and remained significant indicators even after accounting for clinical variables. This review highlights the prognostic value of PROs in both newly diagnosed and relapsed patients, and argues for their use in clinical decision-making and risk assessment at the time of diagnosis and pre-treatment. It also raises the question of how baseline PROs should be used in assessing new treatments within clinical trials in order to identify patients who may respond better to treatments or be in need of pre-treatment adjuvant therapy.
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Disclosures
Campinha-Bacote: Genentech, Inc.: Employment. Trask:Genentech, Inc.: Employment, Equity Ownership. Efficace:Lundbeck: Research Funding; Seattle Genetics: Consultancy; Bristol Myers Squibb: Consultancy; TEVA: Consultancy, Research Funding.