Asia-Pacific Journal of Clinical Oncology

ORIGINAL ARTICLE

Open Access

Physical activity behaviors in cancer survivors treated with neurotoxic chemotherapy

David Mizrahi

The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, New South Wales, Australia

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

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David Goldstein,

Corresponding Author

David Goldstein

[email protected]

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia

Correspondence

David Goldstein, Adult Cancer Program, Level 4, Lowy Bldg, University of New South Wales, Randwick, NSW, 2031, Australia.

Email: [email protected]

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Terry Trinh,

Terry Trinh

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

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Tiffany Li,

Tiffany Li

Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia

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Hannah C. Timmins,

Hannah C. Timmins

Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia

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Michelle Harrison,

Michelle Harrison

Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia

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Gavin M. Marx,

Gavin M. Marx

Sydney Adventist Hospital Clinical School, The University of Sydney, Sydney, New South Wales, Australia

Department of Medical Oncology, Sydney Adventist Hospital, Sydney, New South Wales, Australia

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Elizabeth J. Hovey,

Elizabeth J. Hovey

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia

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Craig R. Lewis,

Craig R. Lewis

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia

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Michael Friedlander,

Michael Friedlander

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia

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Susanna B. Park,

Susanna B. Park

Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia

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David Mizrahi,

David Mizrahi

The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, New South Wales, Australia

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

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David Goldstein,

Corresponding Author

David Goldstein

[email protected]

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia

Correspondence

David Goldstein, Adult Cancer Program, Level 4, Lowy Bldg, University of New South Wales, Randwick, NSW, 2031, Australia.

Email: [email protected]

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Terry Trinh,

Terry Trinh

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

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Tiffany Li,

Tiffany Li

Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia

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Hannah C. Timmins,

Hannah C. Timmins

Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia

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Michelle Harrison,

Michelle Harrison

Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia

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Gavin M. Marx,

Gavin M. Marx

Sydney Adventist Hospital Clinical School, The University of Sydney, Sydney, New South Wales, Australia

Department of Medical Oncology, Sydney Adventist Hospital, Sydney, New South Wales, Australia

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Elizabeth J. Hovey,

Elizabeth J. Hovey

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia

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Craig R. Lewis,

Craig R. Lewis

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia

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Michael Friedlander,

Michael Friedlander

Prince of Wales Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia

Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia

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Susanna B. Park,

Susanna B. Park

Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia

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First published: 25 July 2022

https://doi.org/10.1111/ajco.13834

Citations: 1

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Abstract

Aim

There are many barriers to physical activity among cancer survivors. Survivors treated with neurotoxic chemotherapy may develop chemotherapy-induced peripheral neuropathy (CIPN) and experience additional barriers related to sensorimotor and mobility deficits. This study examined physical activity behaviors, including physical activity predictors, among cancer survivors treated with neurotoxic chemotherapies.

Methods

A cross-sectional study of 252 participants, 3–24 months after neurotoxic chemotherapy, was undertaken. Physical activity was self-reported (IPAQ). CIPN was self-reported (FACT/GOG-Ntx-13), clinically graded (NCI-CTCAE), and objectively measured using neurological grading scales and neurophysiological techniques (tibial and sural nerve conduction studies). Balance (Swaymeter) and fine motor skills (grooved pegboard) were assessed. Regression models were used to identify clinical, demographic and CIPN predictors of walking and moderate–vigorous physical activity.

Results

Forty-four percent of participants did not meet recommended physical activity guidelines (≥150 min/week). Sixty-six percent presented with CIPN. Nineteen percent of participants with CIPN reported that symptoms interfered with their ability to be physically active. A lower proportion of survivors aged ≥60, with grade ≥1 CIPN or BMI ≥30, reported meeting physical activity guidelines (all p < .05). Regression models identified older age, higher BMI, and patient-reported CIPN associated with lower walking, while higher BMI and females were associated with lower moderate–vigorous physical activity. Neurologically assessed CIPN did not associate with walking or moderate–vigorous physical activity.

Conclusion

Cancer survivors exposed to neurotoxic chemotherapy have low physical activity levels. Further work should examine the factors causing physical activity limitations in this cohort and designing interventions to improve physical function and quality of life in survivors.

1 INTRODUCTION

Physical activity participation associates with numerous benefits for cancer survivors, including improved general health, sleep quality, muscle mass, quality of life, and survival.¹ However, there are many barriers to participation among cancer survivors, which may reduce their ability or willingness to participate.² Neurotoxic anticancer agents such as taxanes, platinum drugs, vinca alkaloids, or bortezomib³ are utilized to treat a significant proportion of cancer survivors. These agents are associated with the development of chemotherapy-induced peripheral neuropathy (CIPN), which may impair sensation, physical function, balance, and reduce quality of life.⁴ CIPN represents one potential barrier to physical activity, which may make exercise more challenging for survivors. Importantly, structured exercise and balance training are potential rehabilitative options for cancer survivors with CIPN⁵; and accordingly, participation may be important for cancer survivors treated with neurotoxic agents.

Prior studies have investigated the impact of physical activity participation on quality of life in cancer patients treated with neurotoxic chemotherapy.⁶ Colorectal cancer survivors who developed CIPN due to their treatment were less likely to achieve physical activity targets, compared to survivors without CIPN.⁷ However, limited data exist regarding risk factors for reduced general physical activity behaviors in cancer patients treated with neurotoxic anticancer agents. The primary aim of our study was to quantify physical activity behaviors among survivors treated with neurotoxic chemotherapy. Our secondary aim was to investigate whether CIPN symptoms interfered with physical activity, and to identify predictors of walking and moderate–vigorous physical activity among cancer survivors who have been treated with neurotoxic chemotherapy.

2 METHODS

2.1 Participants

Participants treated for stage I–III cancer with neurotoxic anticancer agents were recruited from hospitals in Sydney and Brisbane, Australia, between July 2018 and February 2020. Participants were assessed cross-sectionally from 3 up to 24 months after completing neurotoxic chemotherapy. The study was approved by South-Eastern Sydney Local Health District and Sydney Local Health District (RPAH zone) Human Research Ethics Committees, with informed written consent obtained from each participant. Clinical data were obtained from medical records, including cancer diagnosis information and diabetes status.

2.2 Assessment tools

Participants self-reported physical activity over the previous week using the International Physical Activity Questionnaire (IPAQ) - Short Form, validated in patients with cancer.⁸ Total weekly minutes of physical activity energy expenditure (metabolic equivalent of tasks [MET]) were determined by multiplying weekly minutes of walking (×3), moderate intensity (×4), and vigorous intensity (×8) activity. Total MET-minutes per week were calculated for each intensity and summed together for the total value. One item assessed sedentary behaviors regarding daily sitting hours.⁸

Patient-reported CIPN symptoms were assessed using a validated patient-reported outcome measure (FACT/GOG-Ntx-13), comprising 13-items rated from “not at all” to “very much” (total score 0–52), and reverse scored, with lower scores indicating more severe CIPN.⁹ Participants with symptomatic CIPN were asked an additional single-item question regarding whether their CIPN symptoms impacted their ability to exercise. CIPN severity was clinically graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 neuropathy sensory subscale, which graded CIPN as: grade 0 (no symptoms), grade 1 (symptomatic, not interfering with daily function), grade 2 (moderate sensory symptoms, limiting daily function), grade 3 (severe sensory symptoms, limiting daily function and self-care), and grade 4 (disabling).¹⁰ CIPN was also neurologically graded using the Total Neuropathy Score-clinical and reduced versions (TNSc, TNSr, Johns Hopkins University). TNSc is a composite tool assessing upper and lower limb pin-prick sensory and vibration sensibility, deep tendon reflexes, strength, and patient-reported symptoms.^{11, 12} Each component is graded from 0 (normal) to 4 (severe), with the total score ranging from 0 (no symptoms) to 24 (severe symptoms). Additionally, TNSr included a neurophysiological assessment of tibial motor and sural sensory nerves, using standard nerve conduction protocols,¹³ graded from 0 to 4, with a total composite score of 0–32.

Fine motor skills and manual dexterity were assessed using the grooved pegboard test to assess the time taken (seconds) for participants to place 25 pegs into grooved holes using the dominant hand, with two attempts taken to calculate an average time.¹⁴ Balance was assessed using a Swaymeter (NeuRA [Neuroscience Research Australia], Sydney, Australia) to calculate postural sway,¹⁵ as per prior studies.¹⁶ Participants wore a belt attached to a 50-cm rod, which recorded movements as a surrogate marker of the center of mass on an iPad, calculating total path length (mm). Participants completed four 30-s conditions with the eyes open or closed and on a flat or unstable surface (standing on a piece of foam). Total path length was calculated by summing path lengths from all conditions. For participants unable to complete any condition due to instability, a score of the cohort mean plus 3 standard deviations was utilized to calculate path length as per previous protocols.¹⁷

2.3 Data and statistical analyses

Descriptive data for non-normally distributed data as identified using the Shapiro–Walk test were presented as medians with interquartile range (IQR). Otherwise, data were presented as mean and standard deviation. Participants’ physical activity levels were classified into recommended guidelines (≥150 min/week of moderate–vigorous activity),¹⁸ and converted to total MET-minutes per week (sum of walking, moderate, and vigorous activities). Independent sample t-tests were used to compare the proportion of survivors meeting activity guidelines by CIPN grade, age, body mass index (BMI), and cancer stage. Linear regression analyses were conducted to identify clinical, functional, and CIPN symptom-based predictors of walking and moderate–vigorous physical activity (using patient-reported and neurologically graded CIPN measures [TNSc and TNSr] in separate models). Missing data were calculated using multiple imputations. All analyses were conducted using SPSS Statistics Software V25 (IBM; Armonk, NY) and followed the STROBE reporting guidelines for observational studies.¹⁹

3 RESULTS

3.1 Participant characteristics

In total, 252 participants were assessed at a median of 12 months (IQR 17) following completion of neurotoxic cancer treatment (75% female, n = 188, median age 58 [IQR 18] years; Table 1). The most common treatment agents were taxanes (62%, n = 156) and platinum agents (25%, n = 64). Sixty-six percent (n = 166) were experiencing CIPN symptoms at the time of assessment, including mild CIPN in 31.3% (n = 79; Grade 1), moderate in 29.8% (n = 75; Grade 2), and severe in 4.8% (n = 12; Grade 3].

TABLE 1. Clinical and physical activity characteristics (n = 252)

	Median	IQR
Age, years	58.0	18
Body mass index (m/kg²)	26.1	7
Months since treatment	12	17
Physical activity (min/week)
Walking	210	330
Moderate	90	240
Vigorous	0	120
Total (MET-mins/week)	1657	2580
Sitting (hours/day)	6	4

	n	%
Meeting physical activity guidelines^a	140	56
Sex (female)	188	75
Cancer type
Breast	112	45
Gastro-intestinal	61	24
Gynecological	34	14
Hematological	31	12
Other^b	14	5
Cancer stage^c
I	25	11
II	81	37
III	104	47
Undefined stage I–III	11	5
Neurotoxic treatment agents
Taxane	156	62
Platinum	64	25
Vincristine	20	8
Bortezomib	11	4
Thalidomide	1	.4
Type 2 diabetes	23	9

Abbreviation: IQR, interquartile range.
^a Recommended physical activity guidelines are ≥150 min/week of moderate–vigorous physical activity (walking, moderate, vigorous).¹⁸
^b Other cancers include testicular (n = 5), lung (n = 3), prostate (n = 3), and urothelial (n = 3).
^c Cancer stage for solid tumors.

3.2 Physical activity levels after neurotoxic anticancer treatment

Forty-four percent of the cohort (n = 112) were not achieving recommended guidelines after receiving neurotoxic agents (Figure 1). When asked about physical activity in the previous week, 40% (n = 102) reported undertaking any vigorous intensity activity, 64% (n = 162) reported any moderate-intensity physical activity, and 94% (n = 238) reported undertaking any amount of walking (for >10 min increments). Twenty-eight percent (n = 70) did not participate in any moderate- or vigorous-intensity physical activity, while 2.8% (n = 7) were completely sedentary.

Details are in the caption following the image — **FIGURE 1**
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Percentage of patients who received neurotoxic anticancer agents who achieved recommended physical activity guidelines (150 min/week of moderate–vigorous physical activity), and participation in ≥10 min/week of vigorous, moderate, or walking physical activity. Sedentary denotes participating in <10 min/week of any physical activity intensity

3.3 CIPN symptoms impairing ability to be physically active

Participants with CIPN were asked whether they perceived that their CIPN symptoms impaired their ability to be physically active. A total of 19% (n = 29) of participants with CIPN reported that they felt their CIPN symptoms affected their ability to exercise. These participants demonstrated more severe CIPN as assessed by clinically graded NCI-CTCAE (p < .001) and patient-reported FACT/GOG-Ntx-13 measures (p = .003), compared with participants with CIPN who did not report exercise interference, despite not experiencing worse balance (p = .10). There were no differences in physical activity participation between participants who reported CIPN interfering with ability to exercise and those who did not across any intensity (walking: p = .71, moderate: p = .21, vigorous: p = .83, total MET-min/week: p = .44), although the impaired exercise group reported higher daily sitting hours (p = .03).

3.4 Physical activity levels by clinical characteristics

Physical activity levels were analyzed by clinical characteristics, including age, severity of CIPN, BMI, and cancer stage (Figure 2). A higher proportion of younger participants met physical activity guidelines compared with older participants (<60 years = 65% [n = 86] vs. ≥60 years = 45% [n = 54], p = .002), despite no difference in CIPN severity (p = .13). Among participants with no CIPN (grade 0), 79% (n = 61) met guidelines. This proportion was higher than those with mild (grade 1; 46% [n = 36], p = .001) and moderate/severe CIPN (grade 2/3; 49% [n = 43], p = .004). There was no statistical difference in proportion of patients meeting guidelines between participants with mild versus moderate/severe CIPN (p = .62). A lower proportion of obese participants (≥30.0 kg/m²; 41% [n = 28]) met guidelines compared with healthy weight (<25.0 kg/m²; 66% [n = 64], p < .001) and overweight participants (25.0–29.9 kg/m²; 59% [n = 44], p = .03). However, there was no difference between healthy weight and overweight participants (p = .33). There was no difference in the proportion of participants diagnosed with stage I/II disease (61%, n = 67) compared to stage III disease (53%, n = 57, p = .28) meeting guidelines. There were no differences in physical activity between patients treated with taxanes compared to platinum agents, the two most common treatment types (p = .85).

3.5 Predictors of physical activity among patients treated with neurotoxic agents

To further examine predictors of walking and moderate–vigorous physical activity, linear regression analyses were conducted. Factors contributing to higher walking levels included younger age (p = .026), lower BMI (p = .021), and lower patient-reported CIPN severity (p = .027; Table 2). Factors contributing to higher moderate–vigorous physical activity included male gender (p = .003) and lower BMI (p = .031). Factors that did not statistically contribute to predicting either intensity model included time since treatment, diabetes, fine motor function, and balance (all p > .05). When analyzing the model using neurologically graded CIPN (TNSc), and accounting for nerve conduction studies (TNSr) instead of a patient-reported questionnaire, there was no significant contribution of CIPN severity in either physical activity intensity models (Tables S1 and S2).

TABLE 2. Linear regression to determine factors the multivariable model influencing walking and moderate–vigorous intensity MET-minutes per week of physical activity

	Walking		Moderate–vigorous
	B (95% CI)	p-Value	B (95% CI)	p-Value
Age	−12.0 (−37.1 to −.5)	.026*	−9.1 (−33.9 to 15.7)	.47
Sex	21.1 (−262.0 to 304.3)	.88	−1002.2 (−1657.9 to −346.5)	.003*
Body mass index	−25.4 (−46.9 to −3.8)	.021*	−53.9 (−102.8 to −5.1)	.031*
Months post treatment	6.3 (−9.7 to 22.4)	.44	14.8 (−22.4 to 51.9)	.44
Diabetes	−58.3 (−519.9 to 403.2)	.80	−203.5 (−1276.0 to 868.9)	.71
Fine-motor skills (grooved pegboard; seconds)	−.67 (−6.3 to 4.9)	.82	−8.9 (−22.1 to 4.2)	.18
Balance (path length, mm)	−.28 (−.87 to .32)	.36	−.64 (−2.4 to 1.1)	.45
Patient-reported CIPN (FACT/GOG-Ntx-13; 0–52)	−22.0 (−41.5 to −2.5)	.027*	−8.9 (−55.6 to 37.7)	.71

Note: Results are presented with regression coefficients (B) and 95% confidence intervals. Negative sex value denotes female gender, positive diabetes indicates presence of condition, lower FACT/GOG-Ntx-13 score indicates greater symptoms, higher balance score indicates poorer balance, higher grooved pegboard time indicates reduced fine-motor skills.
* p < .05.

4 DISCUSSION

The primary aim of this study was to examine physical activity behaviors in cancer survivors treated with neurotoxic chemotherapies. Given the associations between moderate–vigorous physical activity and cancer survival,²¹ physical function,²² quality of life,²² mobility,^{23, 24} cardiorespiratory fitness,^{5, 25, 26} and muscle strength,^{5, 25, 26} it is critical to identify barriers to physical activity in cancer survivors to encourage behavior change.

Importantly, 28% of our cohort did not participate in any moderate–vigorous physical activity. Although this proportion is similar to the general Australian population,^{27, 28} it could be argued that physical activity participation is more crucial among cancer survivors given their medical sequelae from treatment and the potential benefits. Physical activity levels vary widely among cancer survivors based on cancer type, age, and other clinical factors, with previous reports of 22%–93% of cancer survivors meeting physical activity guidelines.^29-31 Overall, comparing physical activity levels between studies is difficult due to limitations, including the use of self-reported physical activity, which may introduce intensity misinterpretation³² or overreporting,³³ although self-reported physical activity has been shown to correlate moderately with accelerometer data.³⁴

A secondary aim of our study was to examine predictors of physical activity, including CIPN. However, it should be noted that a limitation of our study is the cross-sectional design and lack of prediagnosis physical activity levels,³⁹ which likely represents an important predictor of posttreatment activity.

Our analysis found associations between patient-reported CIPN, BMI, age, female gender with physical activity. Less obese patients met guidelines compared with overweight patients, similar to previous research in cancer survivor cohorts.^40-42 Importantly, obese cancer survivors have been shown to experience more severe CIPN symptoms,⁴³ have reduced physical function,⁴² and diminished quality of life,⁴⁰ representing an important group to promote behavior change. Similarly, older survivors may benefit from physical activity interventions to mitigate their risk of muscle deconditioning and falls.^{2, 44, 45} Finally, females performed less moderate–vigorous physical activity than males as previously reported.⁴⁶ It should be noted that our cohort was 75% female, due to the large number of paclitaxel-treated breast cancer patients, which potentially affects the representativeness of our results.

We found that patient-reported CIPN severity was associated with reduced walking activity. CIPN may produce balance and gait dysfunction, loss of sensory feedback in lower limbs, and increased anxiety surrounding falls risk,^{16, 38} which may affect ability to be physically active. CIPN is also often associated with co-morbidities and higher BMI,^{35, 38} which may further compound inactivity. However, while prior cross-sectional studies have identified an association between low physical activity and greater severity of CIPN,^{30, 35, 36}^, this remains an association and further studies would be required to examine causal links. Further, exercising from the onset of chemotherapy may have promising potential to ameliorate the onset or severity of CIPN,³⁷ which is another factor that a large-scale prospective study could address.

Interestingly, while patient-reported CIPN was associated with total walking amount, we did not find this association with neurologically graded CIPN. This discrepancy between patient-reported CIPN and clinically graded tools, including the TNSc, has been identified previously,⁴⁷ suggesting that these tools identify different facets of neuropathy. This highlights the importance of assessing patient-reported symptoms, particularly given functional and psychological factors that may be critical determinants of participation in physical activity.⁴⁸

The present study was a multisite, large-scale sample using validated assessment tools, including objective, clinical, and patient-reported measures. While we included a broad-spectrum cohort of patients exposed to neurotoxic chemotherapy, this limits our ability to make specific cancer- or treatment-based conclusions. Our findings may not be generalizable to patients with other complex medical conditions or who are disabled by therapy and are less able to participate in research. Our findings are limited by using patient-reported physical activity measures, which can be overcome by using objective measures such as accelerometers. We did not investigate prediagnosis physical activity, which has been shown to correlate with posttreatment physical activity regardless of symptoms and barriers presented.⁴⁹ Further, it is also plausible that other factors, including social support and self-efficacy, are key moderators of physical activity behavior.²⁰

In total, cancer survivors treated with neurotoxic agents may be at risk of reduced physical activity participation and should be motivated to safely increase their physical activity levels, given its potential to improve functional deficits and quality of life. Further work should canvas the primary causal factors related to reduced physical activity in this cohort and design appropriate interventions.

ACKNOWLEDGMENTS

The authors thank the participants for providing their time for this study, all In Focus study collaborators, and UNSW Stats Central for assisting with data analysis. Cancer Institute NSW Program, Grant Number: 14/TBG/1-05; National Health and Medical Research Council of Australia (NHMRC) Project, Grant Number: 1080521; NHMRC Career Development Fellowship, Grant Number: 1148595

Open access publishing facilitated by The University of Sydney, as part of the Wiley - The University of Sydney agreement via the Council of Australian University Librarians.

CONFLICT OF INTEREST

The authors have no conflicts of interest to declare that are relevant to the content of this article.

AUTHOR CONTRIBUTIONS

David Mizrahi, Susanna B. Park, and David Goldstein were responsible for the conceptualization and design of the study. David Mizrahi and Susanna B. Park were responsible for data analysis and preparing the tables and figures. David Mizrahi, Terry Trinh, Hannah C. Timmins, Tiffany Li, David Goldstein, Michelle Harrison, Gavin M. Marx, Elizabeth J. Hovey, Craig R. Lewis, Michael Friedlander, and Susanna B. Park were responsible for data acquisition and collection. All authors were responsible for writing and editing of the manuscript.

ETHICS APPROVAL

The study was approved by South-Eastern Sydney Local Health District and Sydney Local Health District (RPAH zone) Human Research Ethics Committees.

Open Research

DATA AVAILABILITY STATEMENT

The datasets generated and/or analyzed during the current study are not publicly available due to conditions set out by the approving ethics committee but are available from the corresponding author upon reasonable request.

Supporting Information

REFERENCES

1Demark-Wahnefried W, Schmitz KH, Alfano CM, et al. Weight management and physical activity throughout the cancer care continuum. CA Cancer J Clin. 2018; 68(1): 64-89.
10.3322/caac.21441
PubMed Web of Science® Google Scholar
2Clifford BK, Mizrahi D, Sandler CX, et al. Barriers and facilitators of exercise experienced by cancer survivors: a mixed methods systematic review. Support Care Cancer. 2018; 26(3): 685-700.
10.1007/s00520-017-3964-5
PubMed Web of Science® Google Scholar
3Park SB, Goldstein D, Krishnan AV, et al. Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J Clin. 2013; 63(6): 419-437.
10.3322/caac.21204
PubMed Web of Science® Google Scholar
4Kerckhove N, Collin A, Condé S, Chaleteix C, Pezet D, Balayssac D. Long-term effects, pathophysiological mechanisms, and risk factors of chemotherapy-induced peripheral neuropathies: a comprehensive literature review. Front Pharmacol. 2017; 8: 86.
10.3389/fphar.2017.00086
PubMed Web of Science® Google Scholar
5Kanzawa-Lee GA, Larson JL, Resnicow K, Smith EML. Exercise effects on chemotherapy-induced peripheral neuropathy: a comprehensive integrative review. Cancer Nurs. 2020; 43(3): e172-e185.
10.1097/NCC.0000000000000801
PubMed Web of Science® Google Scholar
6Thomaier L, Jewett P, Brown K, et al. The associations between physical activity, neuropathy symptoms and health-related quality of life among gynecologic cancer survivors. Gynecol Oncol. 2020; 158(2): 361-365.
10.1016/j.ygyno.2020.05.026
PubMed Web of Science® Google Scholar
7Packel LB, Prehn AW, Anderson CL, Fisher PL. Factors influencing physical activity behaviors in colorectal cancer survivors. Am J Health Promot. 2015; 30(2): 85-92.
10.4278/ajhp.140103-QUAN-7
PubMed Web of Science® Google Scholar
8Craig CL, Marshall AL, Sjostrom M, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003; 35(8): 1381-1395.
10.1249/01.MSS.0000078924.61453.FB
PubMed Web of Science® Google Scholar
9Calhoun EA, Welshman EE, Chang CH, et al. Psychometric evaluation of the functional assessment of cancer therapy/Gynecologic Oncology Group-neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer. 2003; 13(6): 741-748.
10.1111/j.1525-1438.2003.13603.x
CAS PubMed Web of Science® Google Scholar
10Trotti 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(3): 176-181.
10.1016/S1053-4296(03)00031-6
PubMed Web of Science® Google Scholar
11Cornblath DR, Chaudhry V, Carter K, et al. Total neuropathy score: validation and reliability study. Neurology. 1999; 53(8): 1660-1664.
10.1212/WNL.53.8.1660
CAS PubMed Web of Science® Google Scholar
12Cavaletti 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(2): 135-141.
10.1111/j.1085-9489.2006.00078.x
CAS PubMed Web of Science® Google Scholar
13Liveson JA, Ma DM. Laboratory Reference for Clinical Neurophysiology. Oxford University Press; 1992.
Google Scholar
14Schmidt SL, Oliveira RM, Rocha FR, Abreu-Villaca Y. Influences of handedness and gender on the grooved pegboard test. Brain Cogn. 2000; 44(3): 445-454.
10.1006/brcg.1999.1204
CAS PubMed Web of Science® Google Scholar
15Sturnieks DL, Arnold R, Lord SR. Balance deficits and functional disability in cancer survivors exposed to neurotoxic cancer treatments. BMC Geriatr. 2011; 11(63).
PubMed Web of Science® Google Scholar
16McCrary, Goldstein D, Trinh T, et al. Balance Deficits and Functional Disability in Cancer Survivors Exposed to Neurotoxic Cancer Treatments. 2019; 17(8): 949.
Google Scholar
17Menant JC, Weber F, Lo J, et al. Strength measures are better than muscle mass measures in predicting health-related outcomes in older people: time to abandon the term sarcopenia? Osteoporos Int. 2017; 28(1): 59-70.
10.1007/s00198-016-3691-7
CAS PubMed Web of Science® Google Scholar
18Cormie P, Atkinson M, Bucci L, et al. Clinical oncology society of Australia position statement on exercise in cancer care. Med J Aust. 2018; 209(4): 184-187.
10.5694/mja18.00199
PubMed Web of Science® Google Scholar
19von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Int J Surg. 2014; 12(12): 1495-1499.
10.1016/j.ijsu.2014.07.013
PubMed Web of Science® Google Scholar
20Chung KH, Park SB, Streckmann F, et al. Mechanisms, mediators, and moderators of the effects of exercise on chemotherapy-induced peripheral neuropathy. Cancers (Basel). 2022; 14(5): 1224.
10.3390/cancers14051224
CAS PubMed Google Scholar
21Cannioto RA, Hutson A, Dighe S, et al. Physical activity before, during, and after chemotherapy for high-risk breast cancer: relationships with survival. J Natl Cancer Inst. 2021; 113(1): 54-63.
10.1093/jnci/djaa046
PubMed Google Scholar
22Campbell KL, Winters-Stone KM, Wiskemann J, et al. Exercise guidelines for cancer survivors: consensus statement from international multidisciplinary roundtable. Med Sci Sports Exerc. 2019; 51(11): 2375-2390.
10.1249/MSS.0000000000002116
PubMed Web of Science® Google Scholar
23McCrary JM, Goldstein D, Sandler CX, et al. Exercise-based rehabilitation for cancer survivors with chemotherapy-induced peripheral neuropathy. Support Care Cancer. 2019; 27(10): 3849-3857.
10.1007/s00520-019-04680-w
PubMed Web of Science® Google Scholar
24Kleckner IR, Kamen C, Gewandter JS, et al. Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial. Support Care Cancer. 2018; 26(4): 1019-1028.
10.1007/s00520-017-4013-0
PubMed Web of Science® Google Scholar
25Brayall P, Donlon E, Doyle L, Leiby R, Violette K. Physical therapy–based interventions improve balance, function, symptoms, and quality of life in patients with chemotherapy-induced peripheral neuropathy: a systematic review. Rehabil Oncol. 2018; 36(3): 161-166.
10.1097/01.REO.0000000000000111
Web of Science® Google Scholar
26Mols F, Beijers T, Vreugdenhil G, van de Poll-Franse L. Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review. Support Care Cancer. 2014; 22(8): 2261-2269.
10.1007/s00520-014-2255-7
PubMed Web of Science® Google Scholar
27Bennie JA, Pedisic Z, van Uffelen JGZ, et al. The descriptive epidemiology of total physical activity, muscle-strengthening exercises and sedentary behaviour among Australian adults - results from the National Nutrition and Physical Activity Survey. BMC Public Health. 2016; 16(1): 73.
10.1186/s12889-016-2736-3
PubMed Web of Science® Google Scholar
28 Australian Bureau of Statistics. National Health Survey: First Results, 2014–15 - Exercise. Statistics. Australian Bureau of Statistics; 2015.
Google Scholar
29Neil SE, Gotay CC, Campbell KL. Physical activity levels of cancer survivors in Canada: findings from the Canadian Community Health Survey. J Cancer Surviv. 2014; 8(1): 143-149.
10.1007/s11764-013-0322-6
CAS PubMed Web of Science® Google Scholar
30Mols F, Beijers AJM, Vreugdenhil G, Verhulst A, Schep G, Husson O. Chemotherapy-induced peripheral neuropathy, physical activity and health-related quality of life among colorectal cancer survivors from the PROFILES registry. J Cancer Surviv. 2015; 9(3): 512-522.
10.1007/s11764-015-0427-1
PubMed Web of Science® Google Scholar
31Wilcoxon A, Kober KM, Viele C, et al. Association between physical activity levels and chemotherapy-induced peripheral neuropathy severity in cancer survivors. Oncol Nurs Forum. 2020; 47(6): 703-719.
10.1188/20.ONF.703-719
PubMed Web of Science® Google Scholar
32Götte M, Seidel CC, Kesting SV, Rosenbaum D, Boos J. Objectively measured versus self-reported physical activity in children and adolescents with cancer. PLoS One. 2017; 12(2):e0172216.
10.1371/journal.pone.0172216
PubMed Web of Science® Google Scholar
33Tucker JM, Welk GJ, Beyler NK. Physical activity in U.S.: adults compliance with the physical activity guidelines for Americans. Am J Prev Med. 2011; 40(4): 454-461.
10.1016/j.amepre.2010.12.016
PubMed Web of Science® Google Scholar
34Sloane R, Snyder DC, Demark-Wahnefried W, Lobach D, Kraus WE. Comparing the 7-day physical activity recall with a triaxial accelerometer for measuring time in exercise. Med Sci Sports Exerc. 2009; 41(6): 1334-1340.
10.1249/MSS.0b013e3181984fa8
PubMed Web of Science® Google Scholar
35Battaglini E, Goldstein D, Grimison P, McCullough S, Mendoza-Jones P, Park S. Chemotherapy-induced peripheral neurotoxicity in cancer survivors: predictors of long-term patient outcomes. J Natl Compr Cancer Netw. 2021; 19(7): 821-828.
10.6004/jnccn.2021.7026
CAS PubMed Web of Science® Google Scholar
36Webber K, Carolus E, Mileshkin L, et al. OVQUEST – life after the diagnosis and treatment of ovarian cancer - an international survey of symptoms and concerns in ovarian cancer survivors. Gynecol Oncol. 2019; 155(1): 126-134.
10.1016/j.ygyno.2019.08.009
PubMed Web of Science® Google Scholar
37Lopez-Garzon M, Cantarero-Villanueva I, Postigo-Martin P, González-Santos Á, Lozano-Lozano M, Galiano-Castillo N. Can physical exercise prevent chemotherapy-induced peripheral neuropathy in patients with cancer? A systematic review and meta-analysis. Arch Phys Med Rehabil. 2022. https://doi.org/10.1016/j.apmr.2022.02.008
10.1016/j.apmr.2022.02.008
PubMed Web of Science® Google Scholar
38Winters-Stone KM, Horak F, Jacobs PG, et al. Falls, functioning, and disability among women with persistent symptoms of chemotherapy-induced peripheral neuropathy. J Clin Oncol. 2017; 35(23): 2604-2612.
10.1200/JCO.2016.71.3552
PubMed Web of Science® Google Scholar
39Fassier P, Zelek L, Partula V, et al. Variations of physical activity and sedentary behavior between before and after cancer diagnosis: results from the prospective population-based NutriNet-Santé cohort. Medicine (Baltimore). 2016; 95(40):e4629.
10.1097/MD.0000000000004629
PubMed Web of Science® Google Scholar
40Basen-Engquist K, Scruggs S, Jhingran A, et al. Physical activity and obesity in endometrial cancer survivors: associations with pain, fatigue, and physical functioning. Am J Obstet Gynecol. 2009; 200(3): 288.e1-8.
10.1016/j.ajog.2008.10.010
PubMed Web of Science® Google Scholar
41Beasley JM, Kwan ML, Chen WY, et al. Meeting the physical activity guidelines and survival after breast cancer: findings from the after breast cancer pooling project. Breast Cancer Res Treat. 2012; 131(2): 637-643.
10.1007/s10549-011-1770-1
PubMed Web of Science® Google Scholar
42Blanchard CM, Stein K, Courneya KS. Body mass index, physical activity, and health-related quality of life in cancer survivors. Med Sci Sports Exerc. 2010; 42(4): 665-671.
10.1249/MSS.0b013e3181bdc685
PubMed Web of Science® Google Scholar
43Timmins HC, Mizrahi D, Li T, Kiernan MC, Goldstein D, Park SB. Metabolic and lifestyle risk factors for chemotherapy-induced peripheral neuropathy in taxane and platinum-treated patients: a systematic review. J Cancer Surviv. 2021. https://doi.org/10.1007/s11764-021-00988-x
10.1007/s11764?021?00988?x
Web of Science® Google Scholar
44Tarasenko Y, Chen C, Schoenberg N. Self-reported physical activity levels of older cancer survivors: results from the 2014 national health interview survey. J Am Geriatr Soc. 2017; 65(2): e39-e44.
10.1111/jgs.14589
PubMed Web of Science® Google Scholar
45Schwenk M, Grewal GS, Holloway D, Muchna A, Garland L, Najafi B. Interactive sensor-based balance training in older cancer patients with chemotherapy-induced peripheral neuropathy: a randomized controlled trial. Gerontology. 2016; 62(5): 553-563.
10.1159/000442253
PubMed Web of Science® Google Scholar
46LeMasters TJ, Madhavan SS, Sambamoorthi U, Kurian S. Health behaviors among breast, prostate, and colorectal cancer survivors: a US population-based case-control study, with comparisons by cancer type and gender. J Cancer Surviv. 2014; 8(3): 336-348.
10.1007/s11764-014-0347-5
PubMed Web of Science® Google Scholar
47Alberti 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(1): 257-264.
10.1093/annonc/mdt409
CAS PubMed Web of Science® Google Scholar
48Hiensch AE, Bolam KA, Mijwel S, May AM, Wengström Y. Sense of coherence and its relationship to participation, cancer-related fatigue, symptom burden, and quality of life in women with breast cancer participating in the OptiTrain exercise trial. Support Care Cancer. 2020; 28(11): 5371-5379.
10.1007/s00520-020-05378-0
PubMed Web of Science® Google Scholar
49Granger CL, Connolly B, Denehy L, et al. Understanding factors influencing physical activity and exercise in lung cancer: a systematic review. Support Care Cancer. 2017; 25(3): 983-999.
10.1007/s00520-016-3484-8
PubMed Web of Science® Google Scholar

Citing Literature

Volume19, Issue1

February 2023

Pages 243-249

Filename	Description
ajco13834-sup-0001-tableS1.docx15.5 KB	Table S1
ajco13834-sup-0002-tableS2.docx16.1 KB	Table S2

Physical activity behaviors in cancer survivors treated with neurotoxic chemotherapy

Abstract