Impact of Pain on Symptom Burden in Chemotherapy-Induced Peripheral Neurotoxicity

Authors:
Fawaz Mayez Mahfouz Brain and Mind Centre, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia

Search for other papers by Fawaz Mayez Mahfouz in
Current site
Google Scholar
PubMed
Close
 BAdvSc
,
Tiffany Li Brain and Mind Centre, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia

Search for other papers by Tiffany Li in
Current site
Google Scholar
PubMed
Close
 MBiostat
,
Hannah C. Timmins Brain and Mind Centre, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia

Search for other papers by Hannah C. Timmins in
Current site
Google Scholar
PubMed
Close
 PhD
,
Lisa G. Horvath Chris O’Brien Lifehouse, Camperdown, Australia
Sydney Medical School, The University of Sydney, Camperdown, Australia
Royal Prince Alfred Hospital, Camperdown, Australia

Search for other papers by Lisa G. Horvath in
Current site
Google Scholar
PubMed
Close
 MBBS, PhD
,
Michelle Harrison Chris O’Brien Lifehouse, Camperdown, Australia

Search for other papers by Michelle Harrison in
Current site
Google Scholar
PubMed
Close
 MBBS
,
Peter Grimison Chris O’Brien Lifehouse, Camperdown, Australia
Sydney Medical School, The University of Sydney, Camperdown, Australia

Search for other papers by Peter Grimison in
Current site
Google Scholar
PubMed
Close
 MBBS, PhD
,
Gavin Marx Sydney Adventist Hospital, Wahroonga, Australia

Search for other papers by Gavin Marx in
Current site
Google Scholar
PubMed
Close
 MBBS
,
David Goldstein Prince of Wales Clinical School, Faculty of Medicine & Health, UNSW Sydney, Randwick, Australia
Department of Medical Oncology, Prince of Wales Hospital, Randwick, Australia

Search for other papers by David Goldstein in
Current site
Google Scholar
PubMed
Close
 MBBS
, and
Susanna B. Park Brain and Mind Centre, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia

Search for other papers by Susanna B. Park in
Current site
Google Scholar
PubMed
Close
 PhD
Restricted access

Background: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects the quality of life of cancer survivors. However, the impact of pain on symptom burden remains undefined. This study aimed to define differences in the clinical symptom profile of patients with painful and nonpainful CIPN. Patients and Methods: A total of 579 participants (median age, 59 years [IQR, 19 years]; F=66%) were assessed cross-sectionally 6 months posttreatment. CIPN severity was graded using multiple methods, including patient-reported outcome measures, a clinically graded scale (NCI-CTCAE), and a neurologic examination score. Participants were classified into subgroups based on patient symptom report, with painful CIPN characterized by the presence of shooting/burning pain, and nonpainful CIPN characterized by the presence of numbness or tingling without shooting/burning pain. Behavioral changes were assessed via structured patient interview regarding symptom impact on sleep, exercise, and treatment-seeking. Results: Among 579 participants, 24% (n=140) reported painful CIPN, 48% (n=280) reported nonpainful CIPN, and 28% (n=159) had no CIPN. Participants with painful CIPN demonstrated higher CIPN severity than those with nonpainful CIPN across multiple measures, including NCI-CTCAE, neurologic grading, and patient report (all P<.05). Participants with painful CIPN were more likely to report that their symptoms affected their ability to exercise (P=.007), produced sleep impairment, and increased treatment-seeking behavior due to their symptoms (both P<.001) compared with participants with nonpainful CIPN. Conclusions: Overall, participants with painful CIPN reported higher scores across all CIPN severity measures, including behavioral changes. This study underlines the need for accurate identification of different CIPN subgroups in hopes of informing better treatment and rehabilitation options for cancer survivors with painful CIPN.

Submitted July 6, 2023; final revision received September 4, 2023; accepted for publication September 5, 2023. Published online February 15, 2024.

Author contributions: Study concept and design: All authors. Data collection: Mahfouz, Li, Timmins, Park. Data analysis and interpretation: Mahfouz, Park. Provision of study participants: Horvath, Harrison, Grimison, Marx, Goldstein. Writing—original draft: Mahfouz. Writing—review and editing: All authors. Final approval of manuscript: All authors.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This study was supported by a Cancer Institute NSW Program Grant (14/TPG/1-05) and a National Health and Medical Research Council of Australia (NHMRC) Project Grant (#1080521). T. Li received a PhD Scholarship from Sydney Cancer Partners through funding from the Cancer Institute NSW (2021/CBG0002). S.B. Park is supported by an NHMRC Career Development Fellowship (#1148595).

Supplementary material: Supplementary material associated with this article is available online at https://doi.org/10.6004/jnccn.2023.7083. The supplementary material has been supplied by the author(s) and appears in its originally submitted form. It has not been edited or vetted by JNCCN. All contents and opinions are solely those of the author. Any comments or questions related to the supplementary materials should be directed to the corresponding author.

Correspondence: Susanna B. Park, PhD, IN FOCUS Research Team, Level 4, Brain and Mind Centre, The University of Sydney, 94 Mallett Street, Camperdown, 2050, NSW, Australia. Email: susanna.park@sydney.edu.au

Supplementary Materials

    • Supplemental Materials (PDF 1.59 MB)
  • Collapse
  • Expand
  • 1.

    Park SB, Goldstein D, Krishnan AV, et al. Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J Clin 2013; 63:419437.

  • 2.

    Bonhof CS, Trompetter HR, Vreugdenhil G, et al. Painful and non-painful chemotherapy-induced peripheral neuropathy and quality of life in colorectal cancer survivors: results from the population-based PROFILES registry. Support Care Cancer 2020; 28:59335941.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Battaglini E, Goldstein D, Grimison P, et al. Chemotherapy-induced peripheral neurotoxicity in cancer survivors: predictors of long-term patient outcomes. J Natl Compr Canc Netw 2021; 19:821828.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Mols F, Beijers T, Lemmens V, et al. Chemotherapy-induced neuropathy and its association with quality of life among 2- to 11-year colorectal cancer survivors: results from the population-based PROFILES registry. J Clin Oncol 2013; 31:26992707.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Bennedsgaard K, Ventzel L, Themistocleous AC, et al. Long-term symptoms of polyneuropathy in breast and colorectal cancer patients treated with and without adjuvant chemotherapy. Cancer Med 2020; 9:51145123.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Hershman DL, Weimer LH, Wang A, et al. Association between patient reported outcomes and quantitative sensory tests for measuring long-term neurotoxicity in breast cancer survivors treated with adjuvant paclitaxel chemotherapy. Breast Cancer Res Treat 2011; 125:767774.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Wolf SL, Barton DL, Qin R, et al. The relationship between numbness, tingling, and shooting/burning pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) as measured by the EORTC QLQ-CIPN20 instrument, N06CA. Support Care Cancer 2012; 20:625632.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Bennedsgaard K, Grosen K, Attal N, et al. Neuropathy and pain after breast cancer treatment: a prospective observational study. Scand J Pain 2022; 23:4958.

  • 9.

    Pachman DR, Qin R, Seisler D, et al. Comparison of oxaliplatin and paclitaxel-induced neuropathy (Alliance A151505). Support Care Cancer 2016; 24:50595068.

  • 10.

    Selvy M, Kerckhove N, Pereira B, et al. Prevalence of chemotherapy-induced peripheral neuropathy in multiple myeloma patients and its impact on quality of life: a single center cross-sectional study. Front Pharmacol 2021; 12:637593.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Albany C, Dockter T, Wolfe E, et al. Cisplatin-associated neuropathy characteristics compared with those associated with other neurotoxic chemotherapy agents (Alliance A151724). Support Care Cancer 2021; 29:833840.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Kanzawa-Lee GA, Knoerl R, Donohoe C, et al. Mechanisms, predictors, and challenges in assessing and managing painful chemotherapy-induced peripheral neuropathy. Semin Oncol Nurs 2019; 35:253260.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Park SB, Alberti P, Kolb NA, et al. Overview and critical revision of clinical assessment tools in chemotherapy-induced peripheral neurotoxicity. J Peripher Nerv Syst 2019; 24(Suppl 2):S1325.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Postma TJ, Aaronson NK, Heimans JJ, et al. The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20. Eur J Cancer 2005; 41:11351139.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Haefeli M, Elfering A. Pain assessment. Eur Spine J 2006; 15(Suppl 1):S1724.

  • 16.

    Bouhassira D, Attal N, Alchaar H, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005; 114:2936.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Bennett BK, Park SB, Lin CS, et al. Impact of oxaliplatin-induced neuropathy: a patient perspective. Support Care Cancer 2012; 20:29592967.

  • 18.

    Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003; 13:176181.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Cavaletti G, Jann S, Pace A, et al. Multi-center assessment of the total neuropathy score for chemotherapy-induced peripheral neurotoxicity. J Peripher Nerv Syst 2006; 11:135141.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Cornblath DR, Chaudhry V, Carter K, et al. Total neuropathy score: validation and reliability study. Neurology 1999; 53:16601664.

  • 21.

    Park SB, Goldstein D, Lin CS, et al. Acute abnormalities of sensory nerve function associated with oxaliplatin-induced neurotoxicity. J Clin Oncol 2009; 27:12431249.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Rolke R, Baron R, Maier C, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 2006; 123:231243.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Van Boven RW, Johnson KO. The limit of tactile spatial resolution in humans: grating orientation discrimination at the lip, tongue, and finger. Neurology 1994; 44:23612366.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Schmidt SL, Oliveira RM, Rocha FR, et al. Influences of handedness and gender on the grooved pegboard test. Brain Cogn 2000; 44:445454.

  • 25.

    Velasco R, Navarro X, Gil-Gil M, et al. Neuropathic pain and nerve growth factor in chemotherapy-induced peripheral neuropathy: prospective clinical-pathological study. J Pain Symptom Manage 2017; 54:815825.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Lavoie Smith EM, Cohen JA, Pett MA, et al. The validity of neuropathy and neuropathic pain measures in patients with cancer receiving taxanes and platinums. Oncol Nurs Forum 2011; 38:133142.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Cavaletti G, Cornblath DR, Merkies IS, et al. The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings. Ann Oncol 2013; 24:454462.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Alberti P, Rossi E, Cornblath DR, et al. Physician-assessed and patient- reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin. Ann Oncol 2014; 25:257264.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Timmins HC, Li T, Kiernan MC, et al. Taxane-induced peripheral neuropathy: differences in patient report and objective assessment. Support Care Cancer 2020; 28:44594466.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Timmins HC, Li T, Kiernan MC, et al. Quantification of small fiber neuropathy in chemotherapy-treated patients. J Pain 2020; 21:4458.

  • 31.

    Geber C, Breimhorst M, Burbach B, et al. Pain in chemotherapy-induced neuropathy—more than neuropathic? Pain 2013; 154:28772887.

  • 32.

    Knoerl R, Chornoby Z, Smith EML. Estimating the frequency, severity, and clustering of SPADE symptoms in chronic painful chemotherapy- induced peripheral neuropathy. Pain Manag Nurs 2018; 19:354365.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Ventzel L, Jensen AB, Jensen AR, et al. Chemotherapy-induced pain and neuropathy: a prospective study in patients treated with adjuvant oxaliplatin or docetaxel. Pain 2016; 157:560568.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Ventzel L, Madsen CS, Karlsson P, et al. Chronic pain and neuropathy following adjuvant chemotherapy. Pain Med 2018; 19:18131824.

  • 35.

    Bennedsgaard K, Ventzel L, Andersen NT, et al. Oxaliplatin- and docetaxel-induced polyneuropathy: clinical and neurophysiological characteristics. J Peripher Nerv Syst 2020; 25:377387.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Lavoie Smith EM, Pang H, Cirrincione C, et al. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy- induced painful peripheral neuropathy: a randomized clinical trial. JAMA 2013; 309:13591367.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Lavoie Smith EM, Pang H, Ye C, et al. Predictors of duloxetine response in patients with oxaliplatin-induced painful chemotherapy-induced peripheral neuropathy (CIPN): a secondary analysis of randomised controlled trial - CALGB/alliance 170601. Eur J Cancer Care (Engl) 2017; 26:10.1111/ecc.12421.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Velasco R, Besora S, Argyriou AA, et al. Duloxetine against symptomatic chemotherapy-induced peripheral neurotoxicity in cancer survivors: a real world, open-label experience. Anticancer Drugs 2021; 32:8894.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Gewandter JS, Kleckner AS, Marshall JH, et al. Chemotherapy-induced peripheral neuropathy (CIPN) and its treatment: an NIH Collaboratory study of claims data. Support Care Cancer 2020; 28:25532562.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Loprinzi CL, Lacchetti C, Bleeker J, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: ASCO guideline update. J Clin Oncol 2020; 38:33253348.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Hange N, Poudel S, Ozair S, et al. Managing chronic neuropathic pain: recent advances and new challenges. Neurol Res Int 2022; 2022:8336561.

  • 42.

    Knoerl R, Lavoie Smith EM, Barton DL, et al. Self-guided online cognitive behavioral strategies for chemotherapy-induced peripheral neuropathy: a multicenter, pilot, randomized, wait-list controlled trial. J Pain 2018; 19:382394.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Cata JP, Weng HR, Lee BN, et al. Clinical and experimental findings in humans and animals with chemotherapy-induced peripheral neuropathy. Minerva Anestesiol 2006; 72:151169.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Grisold W, Cavaletti G, Windebank AJ. Peripheral neuropathies from chemotherapeutics and targeted agents: diagnosis, treatment, and prevention. Neuro Oncol 2012; 14(Suppl 4):iv4554.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Jordan B, Margulies A, Cardoso F, et al. Systemic anticancer therapy-induced peripheral and central neurotoxicity: ESMO-EONS-EANO clinical practice guidelines for diagnosis, prevention, treatment and follow-up. Ann Oncol 2020; 31:13061319.

    • PubMed
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 1729 1729 1200
PDF Downloads 995 995 628
EPUB Downloads 0 0 0