Semin Respir Crit Care Med 2020; 41(03): 377-385
DOI: 10.1055/s-0040-1712099
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The State of the Science in Patient-Reported Outcomes for Patients with Lung Cancer

Canhua Xiao
1   Smilow Cancer Hospital Care Center, Yale School of Nursing, Orange, Connecticut
,
Newton Hurst
2   Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan
,
Benjamin Movsas
2   Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan
› Author Affiliations
Further Information

Publication History

Publication Date:
25 May 2020 (online)

Abstract

Traditionally, clinicians have assumed the primary responsibility for evaluating disease- and treatment-related outcomes. In the past few decades, however, a series of recommendations and standards promulgated by professional societies and regulatory agencies have resulted in increased use of patient-reported outcome (PRO) measures in cancer clinical trials. PROs, such as quality of life (QOL) measures, are important in establishing overall treatment effectiveness in cancer clinical trials, and they can inform clinical decision making. This article discusses the current state of the science in PRO research for patients with lung cancer, the cancer type with the highest incidence rate and the lowest survival rate worldwide. The discussion focuses on (1) PRO and survival; (2) electronic PRO reporting and interventions; (3) PROs and immunotherapy; (4) PRO, biomarkers, and precision health; (5) key issues in applying PROs in clinical trials; and (6) future directions for research.

 
  • References

  • 1 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69 (01) 7-34
  • 2 Cancer today. 2018 . Available at: http://gco.iarc.fr/today/home . Accessed April 28, 2020
  • 3 Hirsch FR, Scagliotti GV, Mulshine JL. , et al. Lung cancer: current therapies and new targeted treatments. Lancet 2017; 389 (10066): 299-311
  • 4 PRO Measures. Use in Medical Product Development to Support Labeling Claims. 2009 . Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims . Accessed April 28, 2020
  • 5 Kluetz PG, O'Connor DJ, Soltys K. Incorporating the patient experience into regulatory decision making in the USA, Europe, and Canada. Lancet Oncol 2018; 19 (05) e267-e274
  • 6 Damm K, Roeske N, Jacob C. Health-related quality of life questionnaires in lung cancer trials: a systematic literature review. Health Econ Rev 2013; 3 (01) 15
  • 7 Basch E, Jia X, Heller G. , et al. Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes. J Natl Cancer Inst 2009; 101 (23) 1624-1632
  • 8 Basch E. Patient-reported outcomes: an essential component of oncology drug development and regulatory review. Lancet Oncol 2018; 19 (05) 595-597
  • 9 Bottomley A, Efficace F, Thomas R, Vanvoorden V, Ahmedzai SH. Health-related quality of life in non-small-cell lung cancer: methodologic issues in randomized controlled trials. J Clin Oncol 2003; 21 (15) 2982-2992
  • 10 Claassens L, van Meerbeeck J, Coens C. , et al. Health-related quality of life in non-small-cell lung cancer: an update of a systematic review on methodologic issues in randomized controlled trials. J Clin Oncol 2011; 29 (15) 2104-2120
  • 11 Saad ED, Adamowicz K, Katz A, Jassem J. Assessment of quality of life in advanced non-small-cell lung cancer: an overview of recent randomized trials. Cancer Treat Rev 2012; 38 (06) 807-814
  • 12 Braun DP, Gupta D, Staren ED. Quality of life assessment as a predictor of survival in non-small cell lung cancer. BMC Cancer 2011; 11: 353
  • 13 Fiteni F, Vernerey D, Bonnetain F. , et al. Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients. Eur J Cancer 2016; 52: 120-128
  • 14 Ganz PA, Lee JJ, Siau J. Quality of life assessment. An independent prognostic variable for survival in lung cancer. Cancer 1991; 67 (12) 3131-3135
  • 15 Kaasa S, Mastekaasa A, Lund E. Prognostic factors for patients with inoperable non-small cell lung cancer, limited disease. The importance of patients' subjective experience of disease and psychosocial well-being. Radiother Oncol 1989; 15 (03) 235-242
  • 16 Langendijk H, Aaronson NK, de Jong JM, ten Velde GP, Muller MJ, Wouters M. The prognostic impact of quality of life assessed with the EORTC QLQ-C30 in inoperable non-small cell lung carcinoma treated with radiotherapy. Radiother Oncol 2000; 55 (01) 19-25
  • 17 Maione P, Perrone F, Gallo C. , et al. Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study. J Clin Oncol 2005; 23 (28) 6865-6872
  • 18 Movsas B, Hu C, Sloan J. , et al. Quality of life analysis of a radiation dose-escalation study of patients with non-small-cell lung cancer: a secondary analysis of the Radiation Therapy Oncology Group 0617 Randomized Clinical Trial. JAMA Oncol 2016; 2 (03) 359-367
  • 19 Movsas B, Moughan J, Sarna L. , et al. Quality of life supersedes the classic prognosticators for long-term survival in locally advanced non-small-cell lung cancer: an analysis of RTOG 9801. J Clin Oncol 2009; 27 (34) 5816-5822
  • 20 Qi Y, Schild SE, Mandrekar SJ. , et al. Pretreatment quality of life is an independent prognostic factor for overall survival in patients with advanced stage non-small cell lung cancer. J Thorac Oncol 2009; 4 (09) 1075-1082
  • 21 Quinten C, Coens C, Mauer M. , et al; EORTC Clinical Groups. Baseline quality of life as a prognostic indicator of survival: a meta-analysis of individual patient data from EORTC clinical trials. Lancet Oncol 2009; 10 (09) 865-871
  • 22 Herndon II JE, Fleishman S, Kornblith AB, Kosty M, Green MR, Holland J. Is quality of life predictive of the survival of patients with advanced nonsmall cell lung carcinoma?. Cancer 1999; 85 (02) 333-340
  • 23 Ediebah DE, Coens C, Zikos E. , et al. Does change in health-related quality of life score predict survival? Analysis of EORTC 08975 lung cancer trial. Br J Cancer 2014; 110 (10) 2427-2433
  • 24 Eton DT, Fairclough DL, Cella D, Yount SE, Bonomi P, Johnson DH. ; Eastern Cooperative Oncology Group. Early change in patient-reported health during lung cancer chemotherapy predicts clinical outcomes beyond those predicted by baseline report: results from Eastern Cooperative Oncology Group Study 5592. J Clin Oncol 2003; 21 (08) 1536-1543
  • 25 Gupta D, Braun DP, Staren ED. Association between changes in quality of life scores and survival in non-small cell lung cancer patients. Eur J Cancer Care (Engl) 2012; 21 (05) 614-622
  • 26 Basch E, Deal AM, Dueck AC. , et al. Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. JAMA 2017; 318 (02) 197-198
  • 27 Brunelli A, Salati M, Refai M. , et al. Development of a patient-centered aggregate score to predict survival after lung resection for non-small cell lung cancer. J Thorac Cardiovasc Surg 2013; 146 (02) 385-90.e1 , 2
  • 28 Chung AE, Shoenbill K, Mitchell SA. , et al. Patient free text reporting of symptomatic adverse events in cancer clinical research using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). J Am Med Inform Assoc 2019; 26 (04) 276-285
  • 29 Schoen MW, Basch E, Hudson LL. , et al. Software for administering the National Cancer Institute's Patient-Reported Outcomes Version of the common terminology criteria for adverse events: usability study. JMIR Human Factors 2018; 5 (03) e10070
  • 30 Read K, LaPolla FWZ. A new hat for librarians: providing REDCap support to establish the library as a central data hub. J Med Libr Assoc 2018; 106 (01) 120-126
  • 31 Harris PA, Taylor R, Minor BL. , et al; REDCap Consortium. The REDCap consortium: building an international community of software platform partners. J Biomed Inform 2019; 95: 103208
  • 32 Maguire R, Fox PA, McCann L. , et al. The eSMART study protocol: a randomised controlled trial to evaluate electronic symptom management using the advanced symptom management system (ASyMS) remote technology for patients with cancer. BMJ Open 2017; 7 (05) e015016
  • 33 Ciani O, Cucciniello M, Petracca F. , et al. Lung Cancer App (LuCApp) study protocol: a randomised controlled trial to evaluate a mobile supportive care app for patients with metastatic lung cancer. BMJ Open 2019; 9 (02) e025483
  • 34 Basch E, Artz D, Iasonos A. , et al. Evaluation of an online platform for cancer patient self-reporting of chemotherapy toxicities. J Am Med Inform Assoc 2007; 14 (03) 264-268
  • 35 Basch E, Deal AM, Kris MG. , et al. Symptom monitoring with patient-reported outcomes during routine cancer treatment: a randomized controlled trial. J Clin Oncol 2016; 34 (06) 557-565
  • 36 Denis F, Viger L, Charron A. , et al. Detection of lung cancer relapse using self-reported symptoms transmitted via an internet web-application: pilot study of the sentinel follow-up. Support Care Cancer 2014; 22 (06) 1467-1473
  • 37 Denis F, Basch E, Septans AL. , et al. Two-year survival comparing web-based symptom monitoring vs routine surveillance following treatment for lung cancer. JAMA 2019; 321 (03) 306-307
  • 38 Denis F, Lethrosne C, Pourel N. , et al. Randomized trial comparing a web-mediated follow-up with routine surveillance in lung cancer patients. J Natl Cancer Inst 2017; 109 (09) 109
  • 39 Lizée T, Basch E, Trémolières P. , et al. Cost-effectiveness of web-based patient-reported outcome surveillance in patients with lung cancer. J Thorac Oncol 2019; 14 (06) 1012-1020
  • 40 Westeel V, Choma D, Clément F. , et al. Relevance of an intensive postoperative follow-up after surgery for non-small cell lung cancer. Ann Thorac Surg 2000; 70 (04) 1185-1190
  • 41 Calman L, Beaver K, Hind D, Lorigan P, Roberts C, Lloyd-Jones M. Survival benefits from follow-up of patients with lung cancer: a systematic review and meta-analysis. J Thorac Oncol 2011; 6 (12) 1993-2004
  • 42 Movsas B, Hunt D, Watkins-Bruner D. , et al. Can electronic web-based technology improve quality of life data collection? Analysis of Radiation Therapy Oncology Group 0828. Pract Radiat Oncol 2014; 4 (03) 187-191
  • 43 Brahmer J, Reckamp KL, Baas P. , et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015; 373 (02) 123-135
  • 44 Gandhi L, Rodríguez-Abreu D, Gadgeel S. , et al; KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 2018; 378 (22) 2078-2092
  • 45 Rittmeyer A, Barlesi F, Waterkamp D. , et al; OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 2017; 389 (10066): 255-265
  • 46 Herbst RS, Baas P, Kim DW. , et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2016; 387 (10027): 1540-1550
  • 47 Reck M, Rodríguez-Abreu D, Robinson AG. , et al; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; 375 (19) 1823-1833
  • 48 Gettinger S, Horn L, Jackman D. , et al. Five-year follow-up of nivolumab in previously treated advanced non-small-cell lung cancer: results from the CA209-003 study. J Clin Oncol 2018; 36 (17) 1675-1684
  • 49 Horn L, Spigel DR, Vokes EE. , et al. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol 2017; 35 (35) 3924-3933
  • 50 Vokes EE, Ready N, Felip E. , et al. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Ann Oncol 2018; 29 (04) 959-965
  • 51 Fehrenbacher L, Spira A, Ballinger M. , et al; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 2016; 387 (10030): 1837-1846
  • 52 Bordoni R, Ciardiello F, von Pawel J. , et al. Patient-reported outcomes in OAK: a phase III study of atezolizumab versus docetaxel in advanced non-small-cell lung cancer. Clin Lung Cancer 2018; 19 (05) 441-449.e4
  • 53 Brahmer JR, Rodríguez-Abreu D, Robinson AG. , et al. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol 2017; 18 (12) 1600-1609
  • 54 Reck M, Brahmer J, Bennett B. , et al. Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. Eur J Cancer 2018; 102: 23-30
  • 55 Reck M, Taylor F, Penrod JR. , et al. Impact of nivolumab versus docetaxel on health-related quality of life and symptoms in patients with advanced squamous non-small cell lung cancer: results from the CheckMate 017 study. J Thorac Oncol 2018; 13 (02) 194-204
  • 56 King-Kallimanis BL, Kanapuru B, Blumenthal GM, Theoret MR, Kluetz PG. Age-related differences in patient-reported outcomes in patients with advanced lung cancer receiving anti-PD-1/PD-L1 therapy. Semin Oncol 2018; 45 (04) 201-209
  • 57 King-Kallimanis BL, Howie LJ, Roydhouse JK. , et al. Patient reported outcomes in anti-PD-1/PD-L1 inhibitor immunotherapy registration trials: FDA analysis of data submitted and future directions. Clin Trials 2019; 16 (03) 322-326
  • 58 Basch E, Leahy AB. Commentary on King-Kallimanis et al.: inadequate measurement of symptomatic adverse events in immunotherapy registration trials. Clin Trials 2019; 16 (03) 327-328
  • 59 What is precision medicine?. 2015 . Available at: https://ghr.nlm.nih.gov/primer/precisionmedicine/definition . Accessed April 28, 2020
  • 60 Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med 2015; 372 (09) 793-795
  • 61 Chatterjee N, Shi J, García-Closas M. Developing and evaluating polygenic risk prediction models for stratified disease prevention. Nat Rev Genet 2016; 17 (07) 392-406
  • 62 Lupski JR. Structural variation mutagenesis of the human genome: impact on disease and evolution. Environ Mol Mutagen 2015; 56 (05) 419-436
  • 63 Amos CI, Wu X, Broderick P. , et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 2008; 40 (05) 616-622
  • 64 Chin LJ, Ratner E, Leng S. , et al. A SNP in a let-7 microRNA complementary site in the KRAS 3′ untranslated region increases non-small cell lung cancer risk. Cancer Res 2008; 68 (20) 8535-8540
  • 65 Jin G, Bae EY, Yang E. , et al. A functional polymorphism on chromosome 15q25 associated with survival of early stage non-small-cell lung cancer. J Thorac Oncol 2012; 7 (05) 808-814
  • 66 Pintarelli G, Cotroneo CE, Noci S. , et al. Genetic susceptibility variants for lung cancer: replication study and assessment as expression quantitative trait loci. Sci Rep 2017; 7: 42185
  • 67 Hampton T. Patients' genes may influence quality of life after cancer chemotherapy. JAMA 2004; 292 (06) 673-674
  • 68 Sprangers MA, Sloan JA, Veenhoven R. , et al. The establishment of the GENEQOL consortium to investigate the genetic disposition of patient-reported quality-of-life outcomes. Twin Res Hum Genet 2009; 12 (03) 301-311
  • 69 Sprangers MA, Thong MS, Bartels M. , et al; GeneQol Consortium. Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update. Qual Life Res 2014; 23 (07) 1997-2013
  • 70 Rausch SM, Clark MM, Patten C. , et al. Relationship between cytokine gene single nucleotide polymorphisms and symptom burden and quality of life in lung cancer survivors. Cancer 2010; 116 (17) 4103-4113
  • 71 Rausch SM, Gonzalez BD, Clark MM. , et al. SNPs in PTGS2 and LTA predict pain and quality of life in long term lung cancer survivors. Lung Cancer 2012; 77 (01) 217-223
  • 72 Sloan JA, de Andrade M, Decker P. , et al. Genetic variations and patient-reported quality of life among patients with lung cancer. J Clin Oncol 2012; 30 (14) 1699-1704
  • 73 Dunn LB, Aouizerat BE, Langford DJ. , et al. Cytokine gene variation is associated with depressive symptom trajectories in oncology patients and family caregivers. Eur J Oncol Nurs 2013; 17 (03) 346-353
  • 74 Reyes-Gibby CC, Spitz M, Wu X. , et al. Cytokine genes and pain severity in lung cancer: exploring the influence of TNF-alpha-308 G/A IL6-174G/C and IL8-251T/A. Cancer Epidemiol Biomarkers Prev 2007; 16 (12) 2745-2751
  • 75 Reyes-Gibby CC, Spitz MR, Yennurajalingam S. , et al. Role of inflammation gene polymorphisms on pain severity in lung cancer patients. Cancer Epidemiol Biomarkers Prev 2009; 18 (10) 2636-2642
  • 76 Reyes-Gibby CC, Swartz MD, Yu X. , et al. Symptom clusters of pain, depressed mood, and fatigue in lung cancer: assessing the role of cytokine genes. Support Care Cancer 2013; 21 (11) 3117-3125
  • 77 Wright F, Hammer M, Paul SM. , et al. Inflammatory pathway genes associated with inter-individual variability in the trajectories of morning and evening fatigue in patients receiving chemotherapy. Cytokine 2017; 91: 187-210
  • 78 Flowers E, Miaskowski C, Conley Y. , et al. Differential expression of genes and differentially perturbed pathways associated with very high evening fatigue in oncology patients receiving chemotherapy. Support Care Cancer 2018; 26 (03) 739-750
  • 79 Bower JE, Ganz PA, Irwin MR, Arevalo JM, Cole SW. Fatigue and gene expression in human leukocytes: increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue. Brain Behav Immun 2011; 25 (01) 147-150
  • 80 Xiao C, Beitler JJ, Higgins KA. , et al. Fatigue is associated with inflammation in patients with head and neck cancer before and after intensity-modulated radiation therapy. Brain Behav Immun 2016; 52: 145-152
  • 81 Xiao C, Beitler JJ, Higgins KA. , et al. Differential regulation of NF-kB and IRF target genes as they relate to fatigue in patients with head and neck cancer. Brain Behav Immun 2018; 74: 291-295
  • 82 Feng LR, Dickinson K, Kline N, Saligan LN. Different phenotyping approaches lead to dissimilar biologic profiles in men with chronic fatigue after radiation therapy. J Pain Symptom Manage 2016; 52 (06) 832-840
  • 83 Hsiao CP, Wang D, Kaushal A, Chen MK, Saligan L. Differential expression of genes related to mitochondrial biogenesis and bioenergetics in fatigued prostate cancer men receiving external beam radiation therapy. J Pain Symptom Manage 2014; 48 (06) 1080-1090
  • 84 Feng LR, Fernández-Martínez JL, Zaal KJM, deAndrés-Galiana EJ, Wolff BS, Saligan LN. mGluR5 mediates post-radiotherapy fatigue development in cancer patients. Transl Psychiatry 2018; 8 (01) 110
  • 85 Smith AK, Conneely KN, Pace TW. , et al. Epigenetic changes associated with inflammation in breast cancer patients treated with chemotherapy. Brain Behav Immun 2014; 38: 227-236
  • 86 Wang A, Ling Z, Yang Z. , et al. Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study. PLoS One 2015; 10 (05) e0126312
  • 87 Lyon DE, Starkweather A, Yao Y. , et al. Pilot study of metabolomics and psychoneurological symptoms in women with early stage breast cancer. Biol Res Nurs 2018; 20 (02) 227-236
  • 88 Fernández-López C, Expósito-Hernández J, Arrebola-Moreno JP. , et al. Trends in phase III randomized controlled clinical trials on the treatment of advanced non-small-cell lung cancer. Cancer Med 2016; 5 (09) 2190-2197
  • 89 Dueck AC, Mendoza TR, Mitchell SA. , et al; National Cancer Institute PRO-CTCAE Study Group. Validity and reliability of the US National Cancer Institute's patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). JAMA Oncol 2015; 1 (08) 1051-1059
  • 90 Movsas B. PROceeding with the Patient-Reported Outcomes (PROs) version of the common terminology criteria for adverse events. JAMA Oncol 2015; 1 (08) 1059-1060
  • 91 Garcia SF, Cella D, Clauser SB. , et al. Standardizing patient-reported outcomes assessment in cancer clinical trials: a patient-reported outcomes measurement information system initiative. J Clin Oncol 2007; 25 (32) 5106-5112
  • 92 Basch E. High compliance rates with patient-reported outcomes in oncology trials submitted to the US Food and Drug Administration. J Natl Cancer Inst 2019; 111 (05) 437-439
  • 93 van der Weijst L, Surmont V, Schrauwen W, Lievens Y. Systematic literature review of health-related quality of life in locally-advanced non-small cell lung cancer: Has it yet become state-of-the-art?. Crit Rev Oncol Hematol 2017; 119: 40-49
  • 94 Rubin DB. Multiple Imputation for Nonresponse in Surveys. Hoboken, NJ: John Wiley & Sons; 2004
  • 95 Calvert M, Blazeby J, Altman DG, Revicki DA, Moher D, Brundage MD. ; CONSORT PRO Group. Reporting of patient-reported outcomes in randomized trials: the CONSORT PRO extension. JAMA 2013; 309 (08) 814-822
  • 96 Bottomley A, Pe M, Sloan J. , et al; Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) consortium. Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards. Lancet Oncol 2016; 17 (11) e510-e514
  • 97 Quené H, Bergh H. On multi-level modeling of data from repeated measures designs: a tutorial. Speech Commun 2004; 43: 103-121
  • 98 Beacon HJ, Thompson SG. Multi-level models for repeated measurement data: application to quality of life data in clinical trials. Stat Med 1996; 15 (24) 2717-2732
  • 99 Bonnetain F, Fiteni F, Efficace F, Anota A. Statistical challenges in the analysis of health-related quality of life in cancer clinical trials. J Clin Oncol 2016; 34 (16) 1953-1956