Patient-reported outcomes in the evaluation of toxicity of anticancer treatments

Journal name:
Nature Reviews Clinical Oncology
Volume:
13,
Pages:
319–325
Year published:
DOI:
doi:10.1038/nrclinonc.2015.222
Published online
Corrected online

Abstract

Symptomatic toxicities associated with anticancer treatments, such as nausea and vomiting, are frequently underreported by clinicians, even when data are prospectively collected within clinical trials. Such underreporting can result in an underestimation of the absolute rate of toxicity, which is highly relevant information for patients and their physicians in clinical practice, and for regulatory authorities. Systematic collection of patient-reported outcomes (PROs) has been demonstrated to be a valid, reliable, feasible and precise approach to tabulating symptomatic toxicities and enables symptoms that are missed by clinicians to be detected. In this Perspectives, the barriers and challenges that should be addressed when considering broad integration of PRO toxicity monitoring in oncology clinical trials are discussed, including challenges related to data collection logistics, analytical approaches, and resource utilization. Instruments conceived to enable description of treatment-related adverse effects, from the patient perspective, bring the potential to improve risk-versus-benefit analyses in clinical research, and to provide patients with accurate information, on the basis of previous experiences of their peers.

At a glance

Figures

  1. Underreporting of treatment-related toxicities by physicians, relative to patients with either advanced-stage lung cancer, or early-stage breast cancer.
    Figure 1: Underreporting of treatment-related toxicities by physicians, relative to patients with either advanced-stage lung cancer, or early-stage breast cancer.

    Underreporting of toxicities is defined as the proportion of patients with self-reported treatment-associated toxicities in any of the treatment cycles that were not reported at all by their physician. Data are from three randomized controlled trials25.

  2. Underreporting by physicians of specific treatment-associated symptoms by physicians in the TORCH trial.
    Figure 2: Underreporting by physicians of specific treatment-associated symptoms by physicians in the TORCH trial.

    In this phase III randomized controlled trial, relative efficacies of chemotherapy (cisplatin plus gemcitabine) versus erlotinib as first-line treatments of patients with advanced-stage non-small-cell lung cancer were investigated. These data suggest that physicians are more accurate in reporting adverse effects that are expected with each specific treatment — nausea and vomiting with cisplatin plus gemcitabine, and diarrhoea with erlotinib25.

  3. Possible modalities for reconciliation of patient's and physician's report of symptomatic treatment-associated toxicities.
    Figure 3: Possible modalities for reconciliation of patient's and physician's report of symptomatic treatment-associated toxicities.

    a | Patient reports are shared with investigators in real time during the patients' visit to the clinic. b | Patient and investigator reports are collected separately and reconciled at the time of analysis. c | Patient and investigator reports are collected and reported separately without any reconciliation.

Change history

Corrected online 27 January 2016
In the original version of this article published online, the title and doi of reference 43 was incorrect. These errors have been corrected in the online and print versions of the article.

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Author information

Affiliations

  1. Massimo Di Maio is at the Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Regione Gonzole 10, 10043 Orbassano (TO), Italy.

  2. Ethan Basch is at the Cancer Outcomes Research Program, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

  3. Jane Bryce and Francesco Perrone are at the Clinical Trials Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori - Fondazione G. Pascale IRCCS, via Mariano Semmola, 80131 Napoli, Italy.

Contributions

All authors researched data for this article, made a substantial contribution to discussions of content, wrote the manuscript and reviewed and/or edited the manuscript prior to submission.

Competing interests statement

E.B. has received research funding from the US National Cancer Institute for developing the PRO–CTCAE. The other authors declare no competing interests.

Corresponding author

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Author details

  • Massimo Di Maio

    Massimo Di Maio is an Associate Professor of Medical Oncology at the Department of Oncology, University of Turin, Italy. He previously worked at the Clinical Trials Unit of the National Cancer Institute 'G.Pascale' Foundation, in Naples, Italy, where he was involved in the planning, conducting and analysis of clinical trials. His main areas of interest are the treatment of solid tumours, methodology of clinical trials in oncology and meta-analyses based on individual patients' data. He has authored more than 150 publications in international peer-reviewed journals.

  • Ethan Basch

    Ethan Basch is a medical oncologist and health services researcher who directs the Cancer Outcomes Research programme at the University of North Carolina, USA. He leads a research programme focused on the development and implementation of patient-reported outcomes (PROs) in oncology drug development, comparative effectiveness research, and routine clinical care. His group developed the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO–CTCAE) under a contract with the US National Cancer Institute, and has tested PROs in myriad trials. His research has determined that clinicians under-detect adverse events and that patient reporting improves the quality of adverse event data.

  • Jane Bryce

    Jane Bryce is a Research Nurse at Istituto Nazionale Tumori – Fondazione G. Pascale in Naples, Italy. Jane is an active researcher in the Clinical Trials Unit, and coordinates its activities in international clinical trials sponsored by the Institute. She completed her graduate education at the University of Pittsburgh, USA, and is a certified Advanced Oncology Clinical Nurse Specialist (AOCNS), an active member of ESMO, ESGO, the European and US Oncology Nursing Societies, International Society of Nurses in Cancer Care (ISNCC) and Multinational Association of Supportive Care in Cancer.

  • Francesco Perrone

    Francesco Perrone is a medical oncologist and Director of the Clinical Trials Unit at the National Cancer Institute of Naples, Italy. From 2005 to March 2012, he served as an adviser to the Italian Drug Agency (the governmental body in charge of reimbursement of new drugs). His main research interest is in lung, gynaecological and breast cancers and, more generally, in clinical trials (including phase I) of innovative drugs for solid tumours. He is the author or co-author of 225 peer-reviewed publications.

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