Chemotherapy and COVID-19: Impact on Health, Strength, and Cardiovascular Risk in Cancer Patients

doi:10.21203/rs.3.rs-3731579/v1

Download PDF

Research Article

Chemotherapy and COVID-19: Impact on Health, Strength, and Cardiovascular Risk in Cancer Patients

https://doi.org/10.21203/rs.3.rs-3731579/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Objective: To evaluate and describe the phase angle profile and anthropometric health and fitness indicators of patients undergoing chemotherapy.

Materials and Method: The sample included 106 adult and elderly cancer patients, with different types of cancer, undergoing chemotherapy treatment, of both sexes (71 women and 35 men). They underwent anthropometric assessment, tetrapolar bioimpedance, anthropometry, handgrip dynamometry and the international physical activity questionnaire (IPAQ).

Results: After the analysis, the Body Mass Index (BMI) showed that 49% had changes in ideal body mass indices (13% below and 36% above ideal). The waist-to-hip ratio of most patients (63.7%) indicated a high (36.4%) and very high (27.3%) risk of developing cardiovascular diseases, with only 27.3% being moderate and 9.1% Low %, with higher risk values in women. In body composition, 62.9% of patients showed important changes in body fat percentage (22.9% below and 35% above recommended), in addition to the high prevalence of reduction in skeletal muscle mass, reaching 76% of those evaluated, indicating possible development of sarcopenia, being more evident in women. The majority of patients also had inadequate strength levels (63.6%), both men and women. Men are approximately 4 times more likely to have an insufficient level of strength. The phase angle with an average below the recommended level was found in 94.8% of the sample. The level of physical activity assessed demonstrated 100% sedentary lifestyle.

Conclusion: With the investigation of the variables proposed in this study, we concluded that patients undergoing chemotherapy during the COVID-19 pandemic period had an insufficient level of physical activity, an inadequate level of muscle strength, anthropometric indices and body composition with negative changes, increased cardiovascular risk and low phase angle of reference values in the majority of the sample, with women having the most unfavorable profile.

The research project was approved by the institutional review board, no. 5.069.269.

chemotherapy

cardiovascular risk

physical activity

The year 2020 bore witness to a global healthcare landscape profoundly challenged by two parallel crises: the relentless march of cancer and the emergence of the COVID-19 pandemic. The major international cancer agencies estimate 19.3 million new cases worldwide in 2020, reflecting that one in five individuals stands at risk of a cancer diagnosis in their lifetime^1,2. In this regard, chemotherapy stands as the most used therapy to treat cancer, which is administered in different ways, including intravenously, orally, intramuscularly, subcutaneously, topically and intrathecally³.

Chemotherapy causes toxicity-related side effects, leading to health issues and death. Notably, all organs can be affected by chemotherapy and its chronic effects include drug resistance, carcinogenicity and infertility⁴. The deleterious effects of chemotherapy are well documented among the oncologic population, but how COVID-19 pandemic impacted these subjects remains ill defined.

During COVID-19, several countries reported a considerable delay in cancer diagnosis^1,5. Moreover, Patients with cancer have a higher risk of being admitted to an intensive care unit requiring invasive ventilators or dying from COVID-19 than patients without cancer due to their systemic immunosuppressive state. Cancer patients tend to be older and have other comorbidities, including hypertension, diabetes and cardiovascular diseases. Taken together, a worse prognosis for COVID-19 is related to this scenario, which highlights the importance of self-isolation measures for these patients. However, social isolation policies have reduced follow-up visits for regular pharmacological cancer treatment, as well as adherence to non-pharmacological recommendations such as physical activity⁶.

The pooled consequences of COVID-19 and cancer picture the importance of constant monitoring of some prognostic-related variables, such as body composition⁷, anthropometric, cardiovascular risk indices^8,9, dynapenia and sarcopenia^10,11 as well as phase angle. These variables are non-invasive with simple application in the clinical practice, for example, bioimpedance phase angle (FA) might indicates cellular health and is widely used as a health status to predict different disease severity and survival in different medical conditions, particularly cancer¹². Therefore, a better characterization of these variables can improve the scientific and clinical knowledge on the prognosis of cancer patients during the COVID-19.

The present study evaluated and described the phase angle profile and anthropometric health and strength indicators essential for a good prognosis of patients undergoing chemotherapy during the COVID-19 pandemic period.

This is an observational study carried out at the chemotherapy outpatient clinic collected between May 2021 to June 2022. The research project was approved by the institutional review board, no. 5.069.269.

Sample

This study included 106 patients, 71 females and 35 males, with different types of cancer, all undergoing chemotherapy treatment.

Inclusion Criteria

The following were considered based on the proposed: (1) voluntary and consented participation; (2) being undergoing chemotherapy treatment; (3) not present musculoskeletal and neurological conditions that prevent the performance of tests and evaluations (4) not have any type of medical contraindication that would make collection unfeasible (5) not have cognitive impairment that makes them unable to understand the commands and perform the tests and exams; (6) not undergoing palliative procedures.

Analysis Protocols

Anthropometry

Anthropometric and body composition parameters were collected before medication administration. For circumference measurements, an anthropometric tape (Sanny®) was used, with a measuring range of 2m, made of flat and flexible steel. Waist, hip and calf circumference measurements were collected. We calculated Body Mass Index (BMI) by dividing the weight by the square of the height. Cardiovascular risk was verified based on the Waist-Hip Ratio (WHR), obtained by dividing the waist (cm) and hip (cm) perimeters. To measure waist circumference, the measuring tape was positioned at the smallest curvature located between the ribs and the iliac crest. To measure the hip perimeter, the measuring tape was positioned in the area with the greatest gluteal protuberance.

Body composition and angle phase (BIA)

The tetrapolar Bioimpedance (BIA) used was Sanny (Model 1011), with the use of electrodes. For measurements using bioimpedance, the subject remained lying on a non-conductive surface (stretcher), in the supine position, with arms and legs abducted at 45° from the body.

The assessment of peripheral muscle strength was carried out using a Lafayette Hydraulic manual dynamometer (Biometrics Ltd), following the current guidelines for handgrip strength (REF).

Physical Activity

The level of general physical activity was analyzed according to the short format of International Physical Activity Questionnaire (IPAQ) and normal week, version 8, validated and used in Brazil¹³.

Statistical analysis

The Shapiro-Wilk and Levene tests were used to verify the nature and homogeneity of data distribution, respectively. The T test for independent samples was used to compare continuous variables, while Fisher's exact test was applied to compare categorical variables between groups (sex and dynamometry). A p value < 0.05 was used for statistical significance. All analyzes were performed using R and RStudio software version 4.2.2.

The main characteristics of the sample were described in Table 1.

Table 1

Demographic data of the sample
Variable	N	Mean	Standard Deviation	Maximum	Minimum
Age (years)	98	54.12	16.18	89	18
Height (meters)	89	1.57	0.94	1.79	1.34
Weight (kg)	90	61.02	13.13	111.3	34
BMI	89	24.79	5.09	49.47	13.62
WHR	87	0.89	0.07	1.12	0.72
Calf Circumference	92	30.66	3.98	43	21
Fat (%)	83	24.09	8.44	43.53	6.77
Phase Angle	78	5.22	1.13	7.98	2.55
Dynamometry	102	27.45	8.5	50	8

106 patients participated in the study, 71 (67%) female and 35 (33%) male. The average age found was 54.10 years. The most frequent diagnosis among the patients analyzed was cancer of the digestive system (23%), hematological cancer (21%), breast cancer (20%), genital cancer (19%), among others (17%).

Patients were found to be thin (13%), eutrophic (51%), overweight (24%) and obese (12%). Our sample showed most patients with altered BMI, below ideal (9.1%) and above ideal (27.3%). Notably, women have a higher BMI than men. Calf circumference is indicative of the possible development of sarcopenia and loss of muscle mass. In our sample, we found most individuals with indexes below normal, 51% of women and 25% of men.

The results related to cardiovascular risk, assessed by the waist-hip ratio, indicated a moderate to very high risk for developing cardiovascular diseases in most patients (63.7%), as shown in Table 2. Moreover, the cardiovascular risk among men is bigger. The strength level of patients is, in the majority (63.6%), at inadequate levels. Only 6% of men had an ideal strength level compared to 30.4% of women.

The phase angle is below that recommended in most patients, with the lowest average prevailing among women. The level of physical activity, assessed by the International Physical Activity Questionnaire (IPAQ), shows that 100% of the sample does not perform enough physical activity to escape a sedentary lifestyle.

Table 2

describes the sex differences among the studied variables. Women presented higher BMIs when compared to men. While men presented higher strength levels, they also presented an increased cardiovascular risk than women.
Table 2. Comparison of variables according to gender
Variables	Female	Male	P Value
Age (years)	52.15 ± 15.58	58.32 ± 17.06	0.08
BMI	25.81 ± 5.38*	22.46 ± 3.59*	0.004*
Strength	23.53 ± 5.55*	35.59 ± 8.35*	0.001*
WHR	0.87 ± 0.07*	0.94 ± 0.07*	0.007*
Calf Circumference	30.59 ± 4.26	30.81 ± 3.48	0.8
WHR = Waist-to-Hip Ratio

Table 3

describes the comparison according to dynamometry. Patients with sufficient dynamometry had greater weight, fat percentage and strength level. For the other variables, no significant differences were observed.
Table 3. Comparison of variables according to dynamometry
Variables	Sufficient	Insufficient	P value
Age (years)	53.06 ± 14.55	54.47 ± 17.42	0.688
BMI	26.04 ± 3.99	24.25 ± 5.64	0.120
Fat (%)	27.04 ± 8.24*	22.24 ± 8.12*	0.004*
Strength	30.86 ± 7.14*	25.66 ± 9*	0.002*
Waist Circumference	86.37 ± 10.05	85.03 ± 10.65	0.561
Hip Circumference	98.98 ± 9.65*	94.12 ± 8.7*	0.01*
WHR	0.88 ± 0.07	0.91 ± 0.08	0.085
Calf Circumference	32.26 ± 3.65*	29.73 ± 3.9*	0.003*

Figure 1 shows the comparison of categorical variables according to gender. Female patients have a higher frequency of normal force than men, but still have a high frequency of low force. Men have a higher frequency of low strength. They are 3.91 times more likely to have an insufficient level of strength compared to women. Both men and women presented insufficient strength values in the majority. The frequency of cardiovascular risk (by WHR) in women indicates the total sample with increased cardiovascular risks. Most men have an increased cardiovascular risk, however, there are individuals with no cardiovascular risk.

Insert Fig. 1 here

Figure 1. Comparison of categorical variables according to sex

Overweight and obesity have become a global problem associated with increased incidence of neoplasms, worsening the prognosis and increasing mortality in cancer patients. Notably, these issues are correlated with metabolic and inflammatory changes that occur in adipose tissue¹⁴. Our study found an increased fat percentage, and decreased lean mass in most of women patients, indicating the possible development of sarcopenia.

Similar to the findings of the present study, a study found that chemotherapy with curative intent had a negative impact on the composition body, physical function, insulin resistance and lipid markers associated with atherosclerotic cardiovascular diseases (ASCVD) in women with breast cancer. They showed that women had changes in adiposity markers, changes in body weight and BMI¹⁵. A single-center retrospective study demonstrated that more than 81% of cancer patients had low muscle mass, 58.8% had low handgrip strength, 68 .2% had low gait speed, and 48.2% were classified as sarcopenic. This scenario is predominant due to frequent weight loss caused by low food intake, increased catabolic pathways, increased inflammation, increased lipolysis and increased proteolysis¹⁶.

A key finding of our study was the increased cardiovascular risk in most patients evaluated, especially female subjects. In contrast to the scientific literature, our study suggested that women generally have a more favorable cardiovascular risk factor profile than men¹⁷.

A prospective observational study evaluated the level of strength of 351 patients admitted to the Oncology Inpatient Unit of the Regional University Hospital of Málaga, to determine the prevalence of malnutrition, low muscle strength, among other health parameters. The number of patients with malnutrition reaches 82%, low BMI in 26.8% and low muscle strength and low fat-free mass reaching 42.2%¹⁸.

Sukackiene et al., (2022)¹⁹ demonstrated that the phase angle is a good predictor of nutritional status and clinical prognosis in several health conditions, including aging, kidney transplant, and cancer. The phase angle of the patients evaluated in this study was below the recommended level. However, women presented lower values than men. Male patients did not present any phase angle that was normal or above the recommended average. The scientific literature has shown that a low phase angle is related to compromised nutritional profile, functional status, decreased quality of life, and increased morbidity and mortality. Taken together, it might be a pivotal indicator of health and integrity, especially in cancer patients²⁰.

This study showed that the sample analyzed has a sedentary profile, where 100% of the sample is in a sedentary state as the goal stipulated by American College of Sports Medicine (ACSM) for cancer patients²¹. This result can be explained by the decrease in physical activity levels and an increase in screen time provoked by the period of social isolation (i.e. time spent in computer, tablet, or watching TV). This behavior is associated with the increase in the consumption of ultra-processed foods, numbers of cigarettes and alcohol intake, indicating a worsening of lifestyles and an increase in health risk behaviors²².

Although the results of the present study highlight a worrying scenario for this population, we cannot affirm that the COVID-19 pandemic was uniquely responsible for these results, but we believe that the lack of physical activity, due to the insecurity caused during the pandemic period, as well as the harmful effects of the disease itself are factors to be investigated and clarified.

Our study had some limitations, including not controlling previous food intake or the type of food ingested; the moment of medication administration, the type of chemotherapy administered during the evaluations, as it was not monitored whether or not the patient being evaluated had taken their medication and which medication they took; the clothing worn by the patient, not being checked if it was unsuitable for collection; the ambient temperature of the location; the sample number could be larger, but during the pandemic access to patients was limited and the number of patients was reduced; At times entry was not permitted.

However, our results show an unfavorable profile in most of the analyzes carried out, making it necessary to advance monitoring to infer whether the pandemic period influenced the results found as well as what consequences they will have on the clinical prognosis. Thus, the analysis instruments used in this research proved to be valuable for monitoring these important variables with effective potential in clinical practice.

Patients undergoing chemotherapy treatment during the COVID-19 pandemic period exhibited insufficient levels of physical activity, presenting concerning values in muscular strength, anthropometry, body composition, cardiovascular risk, and phase angle. Determining whether this phenomenon is a consequence of the pandemic or an evolution of the natural course of the disease in combination with inadequate healthcare measures is a question that needs to be addressed.

ACMS

American College of Sports Medicine

ASCVD

atherosclerotic cardiovascular diseases

BIA

tetrapolar bioimpedance

BMI

body mass index

bioimpedance phase angle

IPAQ

International Physical Activity Questionnaire

WHR

Waist-Hip Ratio

The research project was approved by the Ethics and Research Committee of the University Hospital of the Federal University of Maranhão / HU-UFMA, with embodied opinion no. 5,069,269, following the ethical principles established in Resolution no. 466/12 of the Council National Health Service (CNS) and its supplements. Data collection took place after agreeing to sign the free and informed consent form (TCLE)

Consent for publication.

Not applicable.

Availability of datas and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Competing Interests

The authors declare no competing interests.

Funding

This study was carried out with the authors' own resources

Authors’ contributions

Giérisson Brenno Borges Lima - Data collection, manuscript writing and data analysis

Gabriel Santos de Castro e Lima - Data collection

Flaviana Santos de Sousa Silva - Data collection

Luis Felipe Castro Araújo - Data collection

Thaís da Conceição Tavares Pereira - Data collection

Michel Macedo Monteiro - manuscript review and data analysis

Thiago dos Santos Rosa - manuscript review and data analysis

Hugo de Luca Correa - manuscript review and data analysis

Carlos Eduardo Neves Amorim - Study coordination, manuscript review and data analysis

Acknowledgements

Not applicable

Sung H, Global Cancer Statistics, Camps-Vilaró A et al. Standardized Comparison of Cardiovascular Risk Factors Prevalence in Spanish Women and Men Living with HIV and in the General Population. Journal of personalized medicine. 2021;11(11):1085. 10.3390/jpm11111085.
Carle C, et al. The risk of contracting SARS-CoV-2 or developing COVID-19 for people with cancer: A systematic review of the early evidence. J cancer policy. 2022;33:100338. 10.1016/j.jcpo.2022.100338.
Chargi N, et al. Sarcopenia is a prognostic factor for overall survival in elderly patients with head-and-neck cancer. European archives of oto-rhino-laryngology: official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology -. Head and Neck Surgery. 2019;276(5):1475–86. 10.1007/s00405-019-05361-4.
Clark A, et al. Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study. The Lancet Global Health. 2020;8(8):e1003–17. 10.1016/S2214-109X. (20)30264-3.
Sukackiene D, et al. Standardized Phase Angle for Predicting Nutritional Status of Hemodialysis Patients in the Early Period After Deceased Donor Kidney Transplantation. Front Nutr. 2022;9:803002. 10.3389/fnut.2022.803002.
Iwase T, et al. Body composition and breast cancer risk and treatment: mechanisms and impact. Breast Cancer Res Treat. 2021;186(2):273–83. 10.1007/s10549-020-06092-5.
Petrelli F, et al. Association of Obesity with Survival Outcomes in Patients With Cancer: A Systematic Review and Meta-analysis. JAMA Netw open. 2021;4(3):e213520. 10.1001/jamanetworkopen.2021.3520.
Bull, Caroline J, et al. Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study. BMC Med. 2020;18(1):396. 10.1186/s12916-020-01855-9.
Rechinelli A, Beatriz, et al. Presence of dynapenia and association with anthropometric variables in cancer patients. BMC Cancer. 2020;20(1):1010. 10.1186/s12885-020-07519-4.
Campbell KL, et al. Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable. Med Sci Sports Exerc. 2019;51(11):2375–90. 10.1249/MSS.0000000000002116.
Cruz-Jentoft, Alfonso J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(4):601. 10.1093/ageing/afz046.
Suzuki Y, et al. The phase angle as a predictor of postoperative complications in patients undergoing lung cancer surgery. Surg Today. 2023;53(3):332–7. 10.1007/s00595-022-02564-x.
Contreras-Bolívar V, et al. GLIM Criteria Using Hand Grip Strength Adequately Predict Six-Month Mortality in Cancer Inpatients. Nutrients. 2019;11(9):2043. 10.3390/nu11092043.
Ferlay J, et al. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021. 10.1002/ijc.33588.
Godinho-Mota, Jordana CM, et al. Chemotherapy negatively impacts body composition, physical function and metabolic profile in patients with breast cancer. Clin Nutr. 2021;40(5):3421–8. 10.1016/j.clnu.2020.11.0203.
Instituto Nacional de Câncer. Quimioterapia: orientações aos pacientes. Rio de Janeiro: INCA; 2022.
Jiang N, et al. The Role of Standardized Phase Angle in the Assessment of Nutritional Status and Clinical Outcomes in Cancer Patients: A Systematic Review of the Literature. Nutrients. 2022;15(1). 10.3390/nu15010050.
Malta D, Carvalho et al. A pandemia da COVID-19 e as mudanças no estilo de vida dos brasileiros adultos: um estudo transversal, 2020. Epidemiologia e Serviços de Saúde: Revista do Sistema Único de Saúde do Brasil. 2020;29(4):e2020407. 10.1590/S1679-49742020000400026.
Matsudo SM et al. Nível de atividade física da população do Estado de São Paulo: análise de acordo com o gênero, idade, nível socioeconômico, distribuição geográfica e de conhecimento. Revista Brasileira de Ciência e Movimento. 2002;10(4).
Schirrmacher V. From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment. Int J Oncol. 2019;54(2):407–19. 10.3892/ijo.2018.4661.
Szczyrek Michał, et al. Diet, Microbiome, and Cancer Immunotherapy-A Comprehensive Review. Nutrients. 2021;13(7):2217. 10.3390/nu13072217.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Chemotherapy and COVID-19: Impact on Health, Strength, and Cardiovascular Risk in Cancer Patients

Status:

Version 1

Abstract

Figures

Introduction

Methods

Sample

Inclusion Criteria

Analysis Protocols

Anthropometry

Body composition and angle phase (BIA)

Physical Activity

Statistical analysis

Results

Discussion

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1