|Year : 2020 | Volume
| Issue : 2 | Page : 127-133
Chemotherapy-induced peripheral neuropathy and its correlation with activities of daily living, psychological well-being, grip strength, and quality of life in cancer subjects: An observational study
Renu B Pattanshetty, Anagha Kulkarni, Chinmayi Kulkarni, Manjiri Kulkarni
Department of Oncology Physiotherapy, KAHER Institute of Physiotherapy, Belagavi, Karnataka, India
|Date of Submission||07-Feb-2020|
|Date of Decision||11-Feb-2020|
|Date of Acceptance||08-Sep-2020|
|Date of Web Publication||04-Jan-2021|
Dr. Renu B Pattanshetty
Department of Oncology Physiotherapy, KAHER Institute of Physiotherapy, Nehru Nagar, Belagavi - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
Background and Objective: The incidence of cancer is rapidly rising, resulting in an increase in the number of patients opting for chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the adverse and long-lasting side effects which evidently affects the activities of daily living (ADLs), quality of life, and psychological status. The objective of the present study was to assess for CIPN and find its correlation with grip strength, ADL, psychological variables, and quality of life.
Settings and Design: This was an observational study undertaken in a tertiary care centre and cancer hospital for a period of 6 months.
Materials and Methods: 102 subjects aged between 18 and 70 years were recruited. Subjects were evaluated using Modified Total Neuropathy Score (mTNS), Hand dynamometer, KLE University Institute of Physiotherapy (KLEU-IPT) Objective Functional Assessment Scale, Depression Anxiety Stress Scale (DASS-42), and functional assessment of cancer therapy-general (FACT-G).
Results: CIPN seemed to be more evident in lower limbs than the upper limbs when assessed using mTNS scale. There was a statistical significance in reduction of grip strength (P = 0.00), KLEUIPT-OFS, DASS-42, and FACT-G with significant positive correlation (r = 0.05) with mTNS scores.
Conclusion: CIPN demonstrated to be more pronounced in lower limbs than upper limbs. CIPN has shown to have significant correlation with the grip strength, quality of life, ADLs, depression, and anxiety, suggesting an early physical therapy intervention to avoid such complications.
Keywords: Activity of daily living, Chemotherapy, Chemotherapy-induced peripheral neuropathy, Depression, Grip strength, Quality of life
|How to cite this article:|
Pattanshetty RB, Kulkarni A, Kulkarni C, Kulkarni M. Chemotherapy-induced peripheral neuropathy and its correlation with activities of daily living, psychological well-being, grip strength, and quality of life in cancer subjects: An observational study. Indian J Phys Ther Res 2020;2:127-33
|How to cite this URL:|
Pattanshetty RB, Kulkarni A, Kulkarni C, Kulkarni M. Chemotherapy-induced peripheral neuropathy and its correlation with activities of daily living, psychological well-being, grip strength, and quality of life in cancer subjects: An observational study. Indian J Phys Ther Res [serial online] 2020 [cited 2021 Apr 14];2:127-33. Available from: https://www.ijptr.org/text.asp?2020/2/2/127/190047
| Introduction|| |
Cancer is the uncontrolled growth and spread of cells which invades surrounding tissue and can metastasize to distant sites. The world's population is expected to be 7.5 billion by 2020, with an approximate prediction of about 15.0 million cancer patients, along with death of 12.0 million cancer cases. These figures are likely to grow because of the increase in life span and shift from acute to chronic illness. The treatment options for cancer include hormone therapy, stem cell transplants, radiation therapy, surgery, chemotherapy, and palliative care. Cancer therapies with targeted chemotherapeutic agents make the patient vulnerable for long-term treatment-related side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is a type of neuropathic pain that is a major dose-limiting side effect that develops in alteration to neuromusculoskeletal system.
CIPN is one of the severe side effects, most commonly seen with several chemotherapeutic drugs including platinum agents, taxanes, vinca-alkaloids, and thaladomides. The pathophysiology of development of CIPN includes disrupted microtubule-mediated transport, axonal degeneration; direct damage to dorsal root ganglion (DRG), and mitochondrial dysfunction.,,
CIPN is generally thought to arise as a result of the axoplasmic microtubule-mediated transport disruption and anterograde axonal degeneration, which cause direct damage to sensory nerves of DRG. These pathophysiological changes also affect the daily activities of patient receiving the chemotherapeutic drugs. Loss of muscle power interferes with the independent activities of the patient. However, there is limited literature on assessment of CIPN and its correlation with grip strength, quality of life, psychological variables, and activities of daily living (ADLs). Hence, the present study was undertaken to assess the CIPN and its correlation to the above-mentioned variables.
| Materials and Methods|| |
The study was conducted at a tertiary care hospital and cancer hospital in Belagavi, India. An ethical clearance was obtained from the Institutional Review Committee prior to the commencement of the study. Written informed consent was obtained with detailed explanation in local language including the risks and benefits to all subjects.
102 subjects were recruited from a tertiary health care hospital and cancer hospital in Belagavi, Karnataka, India. The subjects were recruited in the study if they were in the age group of 18–70 years, diagnosed with Stage I, II, III. or IV cancers, and had undergone at least 1 chemotherapy cycle or more and/or were undergoing chemotherapy. The subjects excluded from this study were those who received prior radiation therapy, psychologically unstable subjects, or presence of any central and/or peripheral nervous system.
After finding their suitability as per the inclusion criteria, they were assessed for chemotherapy-induced peripheral neuropathy using the modified total neuropathy score (mTNS) [Figure 1].
Grip strength was measured using a handheld dynamometer with the dominant hand first. The subject was asked to squeeze the dynamometer as much as he/she could and average of 3 readings were taken with 1 min rest in between.
- CIPN was quantified using the mTNS. This scale consists of 5 domains-symptom extension, pin sensibility, vibration sense, muscle strength, and tendon reflexes. These domains are scored from 0 to 4 (minimum to maximum) with the total of this scale being 20. Higher the score, worse is the progression of CIPN
- KLE University-Institute of physiotherapy (KLEUIPT) Objective Functional Scale was used to evaluate the ADLs of subjects postchemotherapy sessions. This scale is divided into two domains, namely, physical (max score-315 and min score-63) and cognitive functions (max score-85 and min score-17). The physical function is further divided into daily ADLs and work-related activities. These domains are scored from 1 to 5, 1 being fully dependent and 5 being fully independent. The total score of this scale is 400, higher the score implies more independence in performing ADLs (r = 0.89)
- Depression Anxiety Stress Scale-42 (DASS-42) analyzed the psychological status of the subjects. This scale comprises 3 domains containing 14 questions each, namely depression, anxiety, and stress. Scoring of the domains ranged from 0 to 3, where 0 implies not applicable whereas 3 implies very much applicable to the subjects. Normative values for depression ranges from 0 to 9, whereas 28 and above indicates extremely severe depression. In case of anxiety, normal values lie between 0–7 while, 20 and above is extremely severe anxiety. Similarly, for stress, 0–14 indicates the normal range whereas 34 and above are extremely stressed (r = 0.85, r = 0.81, r = 0.80) 
- Functional Assessment of Cancer Therapy – General (FACT-G) is a 27 item scale that measures quality of life of an individual within the past 7 days undergoing cancer therapy. It is divided into 4 domains, i.e., physical, social, emotional, and functional well-being. Each domain consists of scoring ranging from 0 to 4, where 0 indicates 'not at all' and 4 indicates 'very much' and is respectively noted. Total score is 108. Higher the score indicates better quality of life.
Statistical analysis was done using SPSS (statistical package of social sciences) Version. 23 to verify the results obtained. Statistical measures such as mean and standard deviation were used to analyze the demographic data. Pearson's correlation coefficient and paired “t” test were used to statistically signify correlation between mTNS and the variables such as grip strength, Functional Assessment of Cancer Therapy-General (FACT-G), and DASS-42. Level of significance was set at Probability value ≤0.05 with power of study 85% and the correlation coefficient set at r = 0.5.
| Results|| |
The demographic data demonstrated that the number of females (61.8%) suffering from cancer were more as compared to males (38.2%). The mean age of males was 52.49 ± 8.91 years and females was 47.87 ± 5.68 years who were undergoing chemotherapy. The average body mass index (BMI) of males was 19.79 ± 2.33 (weight (in kg/height (meters)) and females was 22.13 ± 3.21 [Table 1]. The mean chemotherapy cycles undergone by males was 3.98 ± 2.12 and females was 4.51 ± 2.41 [Table 1]. Overall, mTNS scores when assessed for both upper limbs and lower limbs in all subjects, vibration, and tendon reflex domain of the mTNS scores in both upper limbs and lower limbs showed significant significance (P = 0.00) [Table 2]. Correlation between mTNS scores and the outcome measures demonstrated weak positive correlation with KLEUIPT Objective Functional Scale, DASS-42, and quality of life (QOL) and strong positive correlation with grip strength of high statistical significance (P = 0.00.) [Table 3].
|Table 2: Comparison of various components of modified total neuropathy score scores in upper limb and lower limbs of all the subjects in the study|
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|Table 3: Correlation between modified total neuropathy score scores and outcome measures of all subjects in the study|
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[Table 4] demonstrates the various chemotherapy drugs administered to the study subjects and their mTNS scores in both lower limbs and upper limbs. However, the results obtained could not be analyzed for statistical significance, since the number of the patients administered with the various drugs were small in terms of sample size.
|Table 4: Chemotherapeutic drugs and their relative modified total neuropathy score scores in upper limb and lower limb of all the subjects in the study|
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Correlation of BMI of study subjects with all outcome measures suggested high statistical significance in terms of grip strength of both the dominant and nondominant hands (P = 0.00), depression (P = 0.024), stress (P = 0.029), and physical and functional well-being of FACT-G (P = 0.009, P = 0.018) [Table 5].
|Table 5: Correlation of body mass index and outcome measures of all subjects in the study|
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| Discussion|| |
In the present study, screening of subjects undergoing chemotherapy for CIPN, grip strength, quality of life, functional ADL, and quality of life was evaluated. The subjects were given respective questionnaire to assess the above-mentioned parameter.
The changes that occur with CIPN may be sensory or motor in nature though motor changes solely without sensory symptoms are rare in CIPN. Progressive distal symmetrically distributed symptoms of tingling, pins and needles sensations, numbness, burning, altered sensation, or increased sensitivity that may be painful in the feet and hands are commonly seen. Motor symptoms include weakness in the extremities that is hands and the feet, especially the muscles.,,,, The present study suggested significant affection of CIPN in subjects undergoing chemotherapy. Most of the subjects in the present study had undergone more than one cycle of chemotherapy. As CIPN is featured by motor weakness and sensory symptoms of pain, tingling or numbness, it is often associated with problems like reduction in grip strength, independent functioning of daily activities further causing a negative impact on the psychological aspects and eventually disturbing the quality of life.
Breast cancer is the most common cancer in women in India accounting for 27% of all the cancers. Majority of the subjects were breast cancer survivors undergoing chemotherapy in the present study, which may explain the reason for CIPN more in them. Prasad et al. assessed the peripheral neuropathy in Type 2 diabetes mellitus subjects and found lower mean age group. This may be attributed to early detection and treatment at a relatively early age of onset.
Though BMI was in normal limits in the present study, studies suggest that as the tumor enlarges, the host's muscle mass and adipose mass is reduced. Progressive muscle wasting and anorexia are frequently seen as complications in cancer subjects and thus, resulting in weight loss. Decrease in weight has been correlated with decrease in performance of activities in cancer subjects. The frequency of weight loss has demonstrated with an increase in metastases with males losing significant weight than females., Higher BMI have demonstrated higher prevalence of Peripheral Neuropathy.
Maximum impairments were noted in subjects receiving a combination of leucovorin and 5FU, equally affecting both upper and lower limbs in the present study. Similarly, cyclophosamide when administrated alone showed a high score on mTNS. Cisplatin when administered solely, demonstrated a higher CIPN score in lower limbs than the upper limbs. Minimal impairment was seen in the combination of Adriamycin and vincristine. Six cycles of vincristine seems to alter neuropathic symptoms along with altered bowel function with inability to go upstairs independently, thus affecting the ADLs. Cisplatin in combination in Vitamin E has demonstrated decreased evidence of CIPN (25%) as compared to Cisplatin and paclitaxel (73%). Paclitaxel related to neuropathy may be due to microtubule disruption which is present in the cytoplasm. Paclitaxel causes proliferation and disruption of normal functions of cells because of the formation of abnormal bundles of microtubules which bring about a desired effect on the tumor but may be harmful to normal tissues. Microtubules are necessary for maintaining structural functions of the nerves.
In present study, mTNS scale was used to assess the CIPN. There was increase in mTNS scores of in lower limb with score of 7 when compared to upper limbs with score of 5.46 suggesting lower limbs affection more than the upper limbs. CIPN has also been studied in association with indices of Berg Balance scale, time up and go and FACT-G. CIPN has shown to be correlated with neurotoxicity demonstrating a positive correlation with psychological status and sleep in cancer though sleep quality was not assessed in present study.
The patterns of ADLs in subjects receiving chemotherapy using Karnofsky Performance Status Index, Beck Depression Inventory have demonstrated that women are depressed at the beginning of first cycle demonstrating a significant correlation between ADLs and chemotherapy cycles. However, though ADLs were affected the present study correlation between the chemotherapy cycles and ADLs were not studied.
In case of Functional Assessment of Cancer Therapy-General, a positive correlation was demonstrated between chemotherapy cycle and social-well-being (P = 0.032) domain. Correlating between subject reported QOL and nurse led bedside evaluations of CIPN symptoms demonstrated a weak negative correlation scores with emotional well-being and QOL and following nurse-reported parameters. In the present study, ADLs, work-related activities, and cognitive function were correlated with mTNS scores for Upper Limb and Lower limb as demonstrated in other studies. Chemotherapy is known to cause significant depression in subjects of higher than 50 years of age in both day care centre and in hospital subjects. Postmenopausal women with stage I-III breast cancer and were evaluated for risk factors associated with presence of CIPN reported greater insomnia severity, anxiety and depression Colorectal cancer survivors demonstrated trouble in opening and closing jars due to upper limb muscle weakness leading to loss of grip strength in the upper extremity hence making it difficult to perform domestic activities as observed in the present study.
Grip strength has demonstrated significant positive correlation with the mTNS scores. Grip strength has also been considered as predictors of mortality in elderly suggesting loss of muscle mass and/or increase in adiposity, though the mechanism is not clear. An exploratory study suggests that CIPN results in diverse symptoms being mild to severe, from emotional distress, alterations in functional ability and social role impairment within whole.
| Conclusion|| |
The present study demonstrated increased affection of CIPN in females compared to males due to the heterogeneous distribution of the subjects in the present study with higher affection of neuropathy in the lower limbs than the upper limbs. Overall, the study demonstrated strong correlation with mTNS scores and grip strength and weak correlation with quality of life and ADLs suggesting an early physiotherapy intervention in preventing upper limb neuropathy during the chemotherapy cycles.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Ingole SP, Kakde AU, Bonde PB. A review on statistics of cancer in India. IOSR-JESTFT 2016;10:107-16.
Han Y, Smith MT. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN). Front Pharmacol 2013;4:156.
Chaudhry V, Rowinsky EK, Sartorius SE, Donehower RC, Cornblath DR. Peripheral neuropathy from taxol and cisplatin combination chemotherapy: Clinical and electrophysiological studies. Ann Neurol 1994;35:304-11.
Kautio AL, Haanpää M, Kautiainen H, Kalso E, Saarto T. Burden of chemotherapy-induced neuropathy-A cross-sectional study. Support Care Cancer 2011;19:1991-6.
Smith EM, Cohen JA, Pett MA, Beck SL. The reliability and validity of a modified total neuropathy score-reduced and neuropathic pain severity items when used to measure chemotherapy-induced peripheral neuropathy in patients receiving taxanes and platinums. Cancer Nurs 2010;33:173-83.
Perry MC, Doll DC, Peter C. Chemotherapy-induced peripheral neuropathy. In: Perry's The Chemotherapy Source Book. Ch. 22., 5th
ed. Philadelphia: Lippincott Williams & Wilkins; 2010. p. 257-290.
Volkert W, Hassan A, Hassan MA. Effectiveness of monochromatic infrared photo energy and physical therapy for peripheral neuropathy: Changes in sensation, pain, and balance – A preliminary, multi-center study. Phys Occup Ther Geriatr 2006;24:7-18.
Massy-Westropp NM, Gill TK, Taylor AW, Bohannon RW, Hill CL. Hand Grip Strength: Age and gender stratified normative data in a population-based study. BMC Res Notes 2011;4:127.
Vasquez S, Guidon M, McHugh E, Lennon O, Grogan L, Breathnach OS. Chemotherapy induced peripheral neuropathy: The modified total neuropathy score in clinical practice. Ir J Med Sci 2014;183:53-8.
Kumar S, Fernandes, Sharan R, Mhaske G, Muragod AR, Chitra J. Development of a functional assessment scale for Indian population. Indian J Physiother Occup Ther-An Int J 2017; 11:50-6.
Basha E, Kaya M. Depression, Anxiety and Stress Scale (DASS): The study of validity and reliability. Univers J Educ Res 2016;4:2701-5.
Overcash J, Extermann M, Parr J, Perry J, Balducci L. Validity and reliability of the FACT-G scale for use in the older person with cancer. Am J Clin Oncol 2001;24:591-6.
Quasthoff S, Hartung HP. Chemotherapy-induced peripheral neuropathy. J Neurol 2002;249:9-17.
Hilkens PH, van den Bent MI. Chemotherapy induced peripheral neuropathy. J Perpher Nerv Syst 1997;2:350-61.
Weiss RB. Miscellaneous toxicities. In: DeVita VT Jr., Hellman S, Rosemberg SA, editors. Cancer: Principles and Practice of Oncology. Ch. 54. Vol. 2., 7th
ed. Philadelphia: Lippincott Williams & Wilkins; 2005. p. 8.
Peltier AC, Russell JW. Recent advances in drug-induced neuropathies. Curr Opin Neurol 2002;15:633-8.
Carbo M, Balmaceda C. Peripheral neuropathy in cancer patients. Cancer Invest 2001;19:369-82.
Bao T, Basal C, Seluzicki C, Li SQ, Seidman AD, Mao JJ. Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: Prevalence, risk factors, and fall risk. Breast Cancer Res Treat 2016;159:327-33.
Prasad M, Bronson SC, Warrier T, Badarinath A, Rai S, Baid K, et al
. Evaluation of DNA damage in Type 2 diabetes mellitus patients with and without peripheral neuropathy: A study in South Indian population. J Nat Sci Biol Med 2015;6:80-4.
Lawson DH, Richmond A, Nixon DW, Rudman D. Metabolic approaches to cancer cachexia. Annu Rev Nutr 1982;2:277-301.
Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, et al
. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med 1980;69:491-7.
Palomares MR, Sayre JW, Shekar KC, Lillington LM, Chlebowski RT. Gender influence on weight-loss pattern and survival of nonsmall cell lung carcinoma patients. Cancer 1996;78:2119-26.
Greenlee H, Hershman DL, Shi Z, Kwan ML, Ergas IJ, Roh JM, et al
. BMI, lifestyle factors and taxane-induced neuropathy in breast cancer patients: The pathways study. J Natl Cancer Inst 2017;109:1-8.
Imam EA, Ibrahim A, Palaian S, Ibrahim MI. Prevalence of vincristine induced-peripheral neuropathy among Sudanese cancer patients. J Young Pharm 2016;8:239.
Argyriou AA, Chroni E, Koutras A, Ellul J, Papapetropoulos S, Katsoulas G, et al
. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: A randomized controlled trial. Neurology 2005;64:26-31.
Jain KK. Drug-induced peripheral neuropathies. In: Jain KK, editor. Drug-induced Neurological Disorders. 2nd
ed. Seattle: Hogrefe & Huber; 2001. p. 263-94.
Hong JS, Tian J, Wu LH. The influence of chemotherapy-induced neurotoxicity on psychological distress and sleep disturbance in cancer patients. Curr Oncol 2014;21:174-80.
Kyranou M, Paul SM, Dunn LB, Puntillo K, Aouizerat BE, Abrams G, et al
. Differences in Depression, Anxiety, and Quality of Life Between Women with and without Breast Pain Prior to Breast Cancer Surgery, Eur J Oncol Nurs 2013;17(2):190–5.
Chung C, Kim MJ, Rhee MH, Do HG. Functional status and psychological adjustment in gynecology cancer patients receiving chemotherapy. Korean J Women Health Nurs 2005;11:58-66.
Yoo YS, Cho OH. Relationship between quality of life and nurse-led bedside symptom evaluations in patients with chemotherapy-induced peripheral neuropathy. Asian Nurs Res (Korean Soc Nurs Sci) 2014;8:36-41.
Greene D, Nail LM, Fieler VK, Dudgeon D, Jones LS. A comparison of patient-reported side effects among three chemotherapy regimens for breast cancer. Cancer Pract 1994;2:57-62.
Bhattacharyya S, Bhattacherjee S, Mandal T, Das DK. Depression in cancer patients undergoing chemotherapy in a tertiary care hospital of North Bengal, India. Indian J Public Health 2017;61:14-8.
] [Full text]
Mols F, Beijers T, Lemmens V, van den Hurk CJ, Vreugdenhil G, van de Poll-Franse LV. 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;31:2699-707.
Gale CR, Martyn CN, Cooper C, Sayer AA. Grip strength, body composition, and mortality. Int J Epidemiol 2007;36:228-35.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]