Skip to main content
Log in

Patient-reported (EORTC QLQ-CIPN20) versus physician-reported (CTCAE) quantification of oxaliplatin- and paclitaxel/carboplatin-induced peripheral neuropathy in NCCTG/Alliance clinical trials

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript



Clinical practice guidelines on chemotherapy-induced peripheral neuropathy (CIPN) use the NCI Common Terminology Criteria for Adverse Events (CTCAE), while recent clinical trials employ a potentially superior measure, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (QLQ-CIPN20), a patient-reported outcome (PRO). Practitioners and researchers lack guidance, regarding how QLQ-CIPN20 results relate to the traditional CTCAE during the serial assessment of patients undergoing chemotherapy.


Two large CIPN clinical trial datasets (538 patients) pairing QLQ-CIPN20 and CTCAE outcomes were analyzed using a multivariable linear mixed model with QLQ-CIPN20 score as the outcome variable, CTCAE grade as the main effect, and patient as random effect (accounting for internal correlation of serial measures).


The association between QLQ-CIPN20 scores and CTCAE grades was strong (p < 0.0001), whereby patients with higher CTCAE grade had worse QLQ-CIPN20 scores. Some variation of QLQ-CIPN20 scores was observed based on drug, treatment, and cycle. While there was a marked difference in the mean QLQ-CIPN20 scores between CTCAE grades, the ranges of QLQ-CIPN20 scores within each CTCAE grade were large, leading to large overlap in CIPN20 scores across CTCAE grades.


A strong positive association of QLQ-CIPN20 scores and CTCAE grade provides evidence of convergent validity as well as practical guidance, as to how to quantitatively interpret QLQ-CIPN20 scores at the study level in terms of the traditional CTCAE. The present results also highlight an important clinical caveat, specifically, that conversion of a specific QLQ-CIPN20 score to a specific CTCAE score may not be reliable at the level of an individual patient.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others


  1. Kottschade LA, Sloan JA, Mazurczak MA, Johnson DB, Murphy BP, Rowland KM, Smith DA, Berg AR, Stella PJ, Loprinzi CL (2011) The use of vitamin E for the prevention of chemotherapy-induced peripheral neuropathy: results of a randomized phase III clinical trial. Supportive Care Cancer 19:1769–1777

    Article  Google Scholar 

  2. Hershman DL, Unger JM, Crew KD, Minasian LM, Awad D, Moinpour CM, Hansen L, Lew DL, Greenlee H, Fehrenbacher L, Wade JL III, Wong SF, Hortobagyi GN, Meyskens FL, Albain KS (2013) Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. J Clin Oncol 31:2627–2633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zimmerman C, Atherton PJ, Pachman D, Seisler D, Wagner-Johnston N, Dakhil S, Lafky JM, Qin R, Grothey A, Loprinzi C (2015) MC11C4: a pilot randomized, placebo-controlled, double-blind study of venlafaxine to prevent oxaliplatin-induced neuropathy. Support Care Cancer, 1–8

  4. Mols F, Beijers T, Vreugdenhil G, van de Poll-Franse L (2014) Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review. Support Care Cancer 22:2261–2269

    Article  PubMed  Google Scholar 

  5. Hershman DL, Lacchetti C, Dworkin RH, Smith EML, Bleeker J, Cavaletti G, Chauhan C, Gavin P, Lavino A, Lustberg MB, Paice J, Schneider B, Smith ML, Smith T, Terstriep S, Wagner-Johnston N, Bak K, Loprinzi C (2014) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol, JCO – 2013

  6. Postma TJ, Heimans JJ, Muller MJ, Ossenkoppele GJ, Vermorken JB, Aaronson NK (1998) Pitfalls in grading severity of chemotherapy-induced peripheral neuropathy. Ann Oncol 9:739–744

    Article  CAS  PubMed  Google Scholar 

  7. Pachman DR, Barton DL, Watson JC, Loprinzi CL (2011) Chemotherapy-induced peripheral neuropathy: prevention and treatment. Clinical Pharmacology & Therapeutics 90:377–387

    Article  CAS  Google Scholar 

  8. Cavaletti G, Cornblath DR, Merkies ISJ, Postma TJ, Rossi E, Frigeni B, Alberti P et al (2012) The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings. Ann Oncol 0:1–9

    Google Scholar 

  9. Gilchrist L (2012) Chemotherapy-induced peripheral neuropathy in pediatric cancer patients. Semin Pediatr Neurol 19:9–17

    Article  PubMed  Google Scholar 

  10. Visovsky C (2013) Challenges in the conduct of research: chemotherapy-induced peripheral neuropathy. J Adv Pract Oncol 4:369–371

    PubMed  PubMed Central  Google Scholar 

  11. Liu H, Tan AD, Qin R, Sargent DJ, Grothey A, Buckner JC, Schaefer PL, Sloan JA (2015) Comparing and validating simple measures of patient-reported peripheral neuropathy for oncology clinical trials: NCCTG N0897 (Alliance) a pooled analysis of 2440 patients. SOJ Anesthesiol Pain Manag 2:1–9

    Google Scholar 

  12. Stephens RJ, Hopwood P, Girling DJ, Machin D (1997) Randomized trials with quality of life endpoints: are doctors’ ratings of patients’ physical symptoms interchangeable with patients’ self-ratings? Qual Life Res 6:225–236

    Article  CAS  PubMed  Google Scholar 

  13. Shimozuma K, Ohashi Y, Takeuchi A, Arnishi T, Morita S, Kuroi K et al (2009) Validation of the Patient Neurotoxicity Questionnaire (PNQ) during taxane chemotherapy in a phase III randomized trial of breast cancer: N-SAC BC 02. Support Care Cancer 17:1483–1491

    Article  PubMed  Google Scholar 

  14. Smith EML, Barton DL, Qin R, Steen PD, Aaronson NK, Loprinzi CL (2013) Assessing patient-reported peripheral neuropathy: the reliability and validity of the European Organization for Research and Treatment of Cancer QLQ-CIPN20 Questionnaire. Qual Life Res 22:2787–2799

    Article  Google Scholar 

  15. Postma TJ, Aaronson NK, Heimans JJ, Muller MJ, Hildebrand JG, Delattre JY, Hoang-Xuan K, Lantéri-Minet M, Grant R, Huddart R, Moynihan C (2005) The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20. Eur J Cancer 41(8):1135–1139

    Article  CAS  PubMed  Google Scholar 

  16. Pace A, Nisticó C, Cuppone F, Bria E, Galié E, Graziano G, Natoli G, Sperduti I, Jandolo B, Calabretta F, Tomao S, Terzoli E (2007) Peripheral neurotoxicity of weekly paclitaxel chemotherapy: a schedule or a dose issue? Clinical Breast Cancer 7:550–554

    Article  CAS  PubMed  Google Scholar 

  17. Wenzel LB, Huang HQ, Armstrong DK, Walker JL, Cella D (2007) Health-related quality of life during and after Intraperitoneal versus intravenous chemotherapy for optimally debulked ovarian cancer: a gynecologic oncology group study. J Clin Oncol 25:437–443

    Article  CAS  PubMed  Google Scholar 

  18. Loprinzi CL, Reeves BN, Dakhil SR, Sloan JA, Wolf SL, Burger KN, Kamal A, LeLindqwister NA, Doori GS, Jaslowski AJ, Novotny PJ, Lachance DH (2011) Natural history of paclitaxel-associated acute pain syndrome: prospective cohort study NCCTG N08C1. J Clin Oncol 29:1472–1478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Shinde SS, Seisler D, Soori G, Atherton PJ, Pachman DR, Lafky J, Ruddy KJ, Loprinzi CL (2015) Can pregabalin prevent paclitaxel-associated neuropathy?—An ACCRU pilot trial. Support Care Cancer, 1–7

  20. Barton DL, Wos EJ, Qin R, Mattar BI, Green NB, Lanier S et al (2011) A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA. Support Care Cancer 19:833–841

    Article  PubMed  Google Scholar 

  21. Loprinzi CL, Qin R, Dakhil SR, Fehrenbacher L, Flynn DA, Atherton P, Seisler D, Qamar R, Lewis GC, Grothey A (2014) Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance). J Clin Oncol 32:997–1005

    Article  CAS  PubMed  Google Scholar 

  22. Leal AD, Qin R, Atherton PJ, Haluska P, Behrens RJ, Tiber CH, Watanaboonyakhet P, Weiss M, Adams PT, Dockter TJ, Loprinzi CL, for the Alliance for Clinical Trials in Oncology (2014) North Central Cancer Treatment Group/Alliance trial N08CA—the use of glutathione for prevention of paclitaxel/carboplatin-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled study. Cancer 120:1890–1897

    Article  CAS  PubMed  Google Scholar 

  23. Alberti P, Rossi E, Cornblath DR, Merkies ISJ, Postma TJ, Frigeni B, Bruna J, Velasco R, Argyriou AA, Kalofonos HP, Psimaras D, Ricard D, Pace A, Galiè E, Briani C, Dalla Torre C, Faber CG, Lalisang RI, Boogerd W, Brandsma D, Koeppen S, Hense J, Storey D, Kerrigan S, Schenone A, Fabbri S, Valsecchi MG, Cavaletti G, the CI-PeriNomS Group (2014) Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin. Ann Oncol 25:257–264

    Article  CAS  PubMed  Google Scholar 

  24. Dueck AC, Mendoza TR, Mitchell SA et al (2015) 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 1(8):1051–1059. doi:10.1001/jamaoncol.2015.2639

    Article  PubMed  PubMed Central  Google Scholar 

Download references


The authors wish to thank Dr. Cynthia Lynch from the Mayo Clinic for the accrual contribution to NCCTG N08CA and Dr. Nassim Nabbout from the Wichita NCI Community Oncology Research Program for the accrual contribution to NCCTG N08CB.

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Charles L. Loprinzi or Andreas S. Beutler.

Ethics declarations


Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under the Award Number UG1CA189823 (to the Alliance for Clinical Trials in Oncology NCORP Grant) and U10CA180790 and by the National Institute of Nursing Research (NINR) of the National Institutes of Health (NIH) under Award Number R01NR015259 (to A.S.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of interest

The authors declare that they have no conflicts of interest.

Electronic supplementary material

Table S1

(DOCX 16 kb)

Table S2

(DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Le-Rademacher, J., Kanwar, R., Seisler, D. et al. Patient-reported (EORTC QLQ-CIPN20) versus physician-reported (CTCAE) quantification of oxaliplatin- and paclitaxel/carboplatin-induced peripheral neuropathy in NCCTG/Alliance clinical trials. Support Care Cancer 25, 3537–3544 (2017).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: