Cancer is a global major public health concern that will be placed at the top of the list of causes of death in the
Traditionally, oncologists in tertiary care hospitals have provided the majority of healthcare to and followed up with cancer patients and survivors [
Conventional treatments using chemotherapeutic agents are associated with significant side effects that limit satisfaction with and adherence to these therapeutic modalities [
Many forms of exercise have evolved as promising CAM modalities that many cancer patients and survivors use as adjuvant therapies to complement conventional therapies, to stimulate their immunity against cancer, and/or to suppress cancerous cells. Some of these modalities have shown promising outcomes in animal,
Despite the growing body of evidence on the potential benefits of exercise on stimulating anticancer immunity and suppression of cancerous cells, little was narrated on what knowledge items explaining how exercise might stimulate anticancer immunity and suppress cancerous cells that primary healthcare providers and CAM practitioners need to be equipped with to expand their roles in cancer control and supporting shared decisions with their patients. Cancer education has been recognized as underdeveloped in medical schools, specialty training, continuous education, and professional development [
Currently, a core list of knowledge items that primary healthcare providers and CAM practitioners in Palestine or elsewhere need to know on how exercise and physical activities might stimulate anticancer immunity is lacking. Therefore, this study was conducted to achieve formal consensus among primary healthcare providers and CAM practitioners on a core list of knowledge items that primary healthcare providers and CAM practitioners in Palestine need to know on how exercise might stimulate anticancer immunity and suppress cancerous cells.
In this study, we used a modified Delphi technique to achieve consensus among a panel of experts on a core list of knowledge items related to the role of exercise in stimulating anticancer immunity and suppression of cancerous cells that primary healthcare providers and CAM practitioners should know to enrich their knowledge and expand their understanding of how exercise related physiologic and endocrine changes might impact occurrence of cancer and enhance therapeutic agents used to treat cancer. Figure
A flow diagram illustrating the different stages of the study.
Since its inception, the Delphi technique has evolved as a tool combining qualitative and quantitative approaches to achieve consensus among a panel of participants with prior knowledge of a topic being investigated [
Before conducting the Delphi iterative rounds, we contacted and invited 4 oncologists, 3 exercise and medicine specialists, and 2 researchers who conducted research on the impact of exercise on cancer, 2 cancer patients, and 3 survivors (Figure
To complement and expand the list of knowledge items provided by the key contact experts, we conducted an extensive literature review to search for and identify all potential effects of exercise on stimulating anticancer immunity and suppressing cancerous cells [
We then identified 20 researchers and experts who conducted research and published articles on exercise and cancer (Figure
All knowledge items provided by the interviewees during the interviews, found in the literature, and those suggested by the researchers and experts were phrased by the authors into statements. The statements were compiled into a questionnaire. The questionnaire was piloted for clarity and understanding with 5 primary healthcare providers and 3 CAM practitioners (Figure
In this study, we used a purposive sampling technique to identify, invite, and recruit panelists to compose a panel of healthcare providers and CAM practitioners (Figure
The panelists received questionnaires that contained 3 sections. In the first section, the panelists were requested to include their practice and sociodemographic variables like gender, age, academic degree/specialty, employer, number of years in practice, and approximate number of cancer patients or survivors interacted with per month.
The second section contained 4 questions to explore the views and opinions of the panelists on educating/training primary healthcare providers and CAM practitioners on the role of exercise in stimulating anticancer immunity and suppressing cancerous cells. The panelists were asked (1) if they agreed that there was lack of training/education about the potential roles of exercise in cancer prevention and therapy in the curricula of primary healthcare providers and CAM practitioners, (2) if they thought that there should be more efforts to increase the knowledge of primary health providers and CAM practitioners on how exercise can stimulate anticancer immunity and suppress cancerous cells, and (3) if they though that such training/education might improve healthcare delivery and promote the wellbeing of cancer patients and survivors.
The third section contained a list of 49 knowledge items in the form of statements and the panelists were requested to express the level of their disagreement or agreement on a Likert-scale of 1-9. Voting 1-3 indicated that the panelist disagreed with the statement. This meant that the panelist was of the opinion that the knowledge item was not important and it should not be included in the core list of knowledge items to be considered by educators, trainer, and/or regulatory bodies when designing training/educational intervention and/or continuing education to enrich knowledge and expand understanding of primary healthcare providers and CAM practitioners on how exercise might stimulate anticancer immunity and suppress cancerous cells. Voting 7-9 indicated that the panelist agrees with the statement. This meant that the panelist was of the opinion that the knowledge item was important and it should be included in the core list of knowledge items to be considered by educators, trainer, and/or regulatory bodies when designing training/educational intervention and/or continuing education to enrich knowledge and expand understanding of primary healthcare providers and CAM practitioners on how exercise might stimulate anticancer immunity and suppress cancerous cells. The statement was considered equivocal when the panelists voted 4-6. This meant that the panelist was indecisive on the statement either to be considered as important or not. A space was left after each statement and the panelists were encouraged to include comments qualifying and/or justifying their votes.
Statements that were considered equivocal in the first Delphi round were included into a revised questionnaire and were subjected to a second Delphi round. As in previous studies, we provided the panelists with summaries of the comments made by other anonymous panelists on each comment, median and IQR of the votes on each statement, and a reminder of the panelist’s own votes. The panelists were given a chance to change their votes in view of the comments and votes of the other panelists. The votes of the second Delphi round were analyzed using the same definitions of consensus as in the first Delphi round.
This study was approved by the Institutional Review Board (IRB) of An-Najah National University. The panelists provided consent before taking part in the study knowing that the Delphi technique was a semianonymous method. This meant that the identity of the panelists was known to the investigator but not to the other panelists. Votes and comments weighed equally in the analysis.
A total of 10 out of the 20 researchers and experts who were emailed responded and consented to participate in the study. A total of 3 reminder emails were sent to those who did not respond. The questionnaire was returned by 9 researchers and experts giving a response rate of 45% of those initially invited to take part. The participants were of both genders, belonged to different age groups, from different backgrounds, and with variable extensive experience in exercise and cancer. The participants were from the US, UK, Germany, France, Norway, and Palestine. The researchers and experts rated each item and suggested adding additional items. Researchers and experts suggested adding items related to the molecular mechanisms to enrich knowledge and expand the understanding of primary healthcare providers and CAM practitioners on how exercise related physiologic and endocrine changes might impact cancer. Researchers and experts suggested modifying some items for clarity and promoting understanding. The items were revised accordingly and included in the questionnaire for the Delphi rounds.
Responses were obtained from all the 65 healthcare providers and CAM practitioner panelists in the first Delphi round, giving a response rate of 100%. However, in the second Delphi round, responses were obtained from 58 panelists giving a response rate of 89.2%.
The median age of the panelists was 52 with an IQR of 15 years. Of all panelists, 47 (72.3%) were 45 years old and above. More than half (56.9%) of the panelists were male in gender. The majority (73.9%) of the panelists who took part in this study were either primary healthcare or CAM providers. The majority (61.5%) of the participants were employed in primary healthcare facilities (governmental or private). The majority (83.1%) of the panelists were in practice for more than 10 years. More than half (56.9%) of the panelists interacted with 5-9 patients with or survivors of cancer per month. The detailed practice and sociodemographic variables of the panelists who took part in this study are shown in Table
Detailed practice and sociodemographic variables of the panelists who participated in the study (
Variable | n | % |
---|---|---|
| ||
Male | 37 | 56.9 |
Female | 28 | 43.1 |
| ||
< 45 | 18 | 27.7 |
≥ 45 | 47 | 72.3 |
| ||
MD/PhD | 7 | 10.8 |
MD (primary healthcare provider) | 28 | 43.1 |
MD/public health | 4 | 6.2 |
Oncologist | 6 | 9.2 |
CAM provider | 20 | 30.8 |
| ||
Primary healthcare facility (government) | 31 | 47.7 |
Primary healthcare facility (private) | 9 | 13.8 |
Private practice | 25 | 38.5 |
| ||
5-9 | 11 | 16.9 |
10-14 | 23 | 35.4 |
15-19 | 18 | 27.7 |
≥ 20 | 13 | 20 |
| ||
5-9 | 37 | 56.9 |
10-14 | 17 | 26.2 |
≥ 15 | 11 | 16.9 |
CAM: complementary and alternative medicine; MD: Doctor of Medicine; PhD: Doctor of Philosophy.
When surveyed for their views and opinions, the vast majority (96.6%) of the panelists who took part in this study agreed with the literature that there was a lack of training/education with regard to the potential roles of exercises in stimulating anticancer immunity. Similarly, the vast majority (98.5%) of the panelists were of the opinion that more efforts were needed to increase knowledge of primary health providers and CAM practitioners on how exercise can stimulate anticancer immunity and suppress cancerous cells. The majority (78.5%) of the panelists believed that training/educating primary healthcare providers and CAM practitioners on the roles of exercise would improve healthcare delivery and promote the wellbeing of cancer patients and survivors. The detailed responses of the panelists are shown in Table
Views and opinions of the panelists on educating/training primary healthcare providers and CAM practitioners on the role of exercise in stimulating anticancer immunity and suppressing cancerous cells.
# | Question | n | % |
---|---|---|---|
1 | | ||
Yes | 63 | 96.9 | |
No | 2 | 3.1 | |
2 | | ||
Yes | 64 | 98.5 | |
No | 1 | 1.5 | |
3 | | ||
Yes | 51 | 78.5 | |
No | 14 | 21.5 |
Of the 49 items initially presented to the panelists, consensus was achieved on 29 (59.2%) items in the first Delphi round. Items on which consensus was not achieved in the first Delphi round were included into a revised questionnaire and were subjected to a second iterative Delphi round. In the second Delphi round, consensus was achieved on further 16 (32.7%) items. In total, consensus was achieved on 45 items in 6 categories. Of those, 9 (20.0%) were general items on recommending moderate to vigorous habitual exercise, 16 (35.6%) were related to the effects of habitual exercise on the functions of immune system and exposure to carcinogens, 12 (26.7%) were related to the effects of habitual exercise on anticancer therapies, 3 (6.7%) were related to the effects of habitual exercise on metastasis of cancer, 3 (6.7%) were related to the effects of habitual exercise on metabolism within tumors, and 2 (4.4%) were related to the role of myokines release induced by habitual exercise. Details of these items are shown in Table
The core list of knowledge items on which consensus was achieved to be considered by educators, trainers, and/or health regulatory bodies for designing training/educational course or continuing education for primary healthcare providers and CAM practitioners on the roles of exercise in stimulating anticancer immunity and suppressing cancerous cells.
# | Item | Delphi round on which consensus was achieved |
---|---|---|
| ||
1 | Sedentary lifestyle was observed to be associated with several common types of cancer. | 2 |
2 | Evidence from various epidemiological studies demonstrated that exercise reduced the risks of at least 13 types of cancer including endometrial, colorectal, breast, and lung cancers. | 2 |
3 | Evidence from various epidemiological studies demonstrated that exercise reduced recurrence of colon, prostate, and breast cancer. | 1 |
4 | A growing body of research has demonstrated that exercise improved survival in patients who have developed certain types of cancer. | 2 |
5 | Evidence from various animal studies demonstrated that exercise reduced incidence, growth, and metastasis of tumors. | 1 |
6 | A growing body of research has demonstrated that exercise improved objective physiologic measures related to physical function, body composition, and cardiopulmonary fitness of cancer patients and survivors. | 1 |
7 | A growing body of research has demonstrated that exercise improved reported outcomes related to sleep, fatigue, life satisfaction, and quality of life of cancer patients and survivors. | 1 |
8 | Cancer care providers should know that engaging cancer patients and survivors in exercise might promote their adherence to health life style like healthy diet and quitting smoking. | 1 |
9 | Evidence from various cancer animal models demonstrated that exercise controlled progression of cancer, regulated tumor growth, alleviated side effects of treatment, and improved therapy outcomes. | 1 |
| ||
| ||
1 | Cancer care providers should know that exercise has the potential to reduce the rate of tumor growth. | 1 |
2 | Cancer care providers should know that exercise induced molecular factors that might be capable of interfering with tumor formation. | 1 |
3 | Cancer care providers should know that exercise stimulated the release of catecholamines that activate the Hippo and YAP signaling pathway which is implicated in tumor formation. | 2 |
| ||
| ||
1 | Cancer care providers should know that tumors favored aerobic glycolysis to support high energy demands within rapidly proliferative environments of the tumor. | 1 |
2 | Cancer care providers should know that tumors were susceptible to increased energy stress during exercise. | 1 |
3 | Cancer care providers should know that exercise regulated metabolism within tumors probably through inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (PKB (Akt))/mammalian target of rapamycin (mTOR) (PI3K-Akt-mTOR) signaling pathway. | 2 |
| ||
| ||
1 | Cancer care providers should know that exercise increased the number of natural killer cell and their cytotoxic activity. | 1 |
2 | Cancer care providers should know that exercise increased monocytes and macrophages in number and function. This included increasing their antitumor cytotoxic activity and their ability to produce cytokines that suppressed cancerous cells. | 1 |
3 | Cancer care providers should know that exercise decreased the number and function of proinflammatory monocytes and proinflammatory cytokines. | 1 |
4 | Cancer care providers should know that exercise enhanced T-cell priming and antigen presenting by increasing expression of dendritic cells, interleukin (IL-4), and interferon (IFN- | 1 |
5 | Cancer care providers should know that exercise improved adaptive immunity by increasing the number of naïve CD8+ T-cells, decreasing the number of senescent/exhausted CD4+ and CD8+ T-cells. | 2 |
6 | Cancer care providers should know that exercise mobilized and redistributed cytotoxic immune cells. | 1 |
7 | Cancer care providers should know that exercise increased the levels of chemokines attracting immune cells, natural killer cell-activating receptor ligands, and ligands that reduce blockade check-points of immune cells. | 1 |
8 | Cancer care providers should know that exercise increased the number of neutrophils and their production of antitumor peroxides and free radicals. | 1 |
9 | Cancer care providers should know that exercise increased interferon levels and cytotoxic natural killer and T-cells infiltration of tumors. | 1 |
10 | Cancer care providers should know that exercise decreased levels of lactate resulted from high aerobic glycolysis and thus, reduced suppressive effects of lactate on the functions of cytotoxic immune cells like T-cells. | 2 |
11 | Cancer care providers should know that exercise increased mobilization of cytotoxic immune cells through different mechanisms that involved shear stress induced by blood flow and adrenergic signaling. These immobilized cytotoxic immune cells might identify and eradicate cancerous cells. | 2 |
12 | Cancer care providers should know that habitual exercise might induce hyperthermia which can regulate and delay growth of tumors and increase infiltration of tumors by natural killer cells by increasing the diameter of blood vessels within the tumor. | 1 |
13 | Cancer care providers should know that exercise increased body temperature which in turn induced interleukin (IL-6) trans-signaling and subsequently made blood vessels within the tumor more permissible to cytotoxic cells. | 1 |
14 | Cancer care providers should know that exercise speeded up the passage of food through the large intestine and thus reduced exposure of the colon to carcinogens. | 1 |
15 | Cancer care providers should know that exercise altered fecal pH and modified the intestinal flora and thus reduced formation of carcinogens. | 1 |
16 | Cancer care providers should know that exercise might reduce the conversion of steroids to more potent carcinogens. | 1 |
| ||
| ||
1 | Cancer care providers should know that exercise stimulated skeletal muscles to release myokines. Released myokines like Oncostatin M, Irisin, and SPARC have the potential to inhibit cancer cells | 2 |
2 | Cancer care providers should know that myokines released during exercise stimulated the release of cytokines, which in turn induced the release of interleukins. Interleukins (for example IL-6) were known to promote proliferation, differentiation, and maturation of natural killer and T-cells. | 2 |
| ||
| ||
1 | Cancer care providers should know that exercise had the potential to reduce tumor-induced muscle mass loss. | 2 |
2 | Cancer care providers should know that exercise might help reduce intramuscular protein degradation associated with chemotherapeutic agents. | 2 |
3 | Cancer care providers should know that exercise might induce the hormone ghrelin which induced appetite and reduced anorexia. | 2 |
4 | Cancer care providers should know that exercise had the potential to stimulate the release of anti-inflammatory cytokines and reduce the levels of proinflammatory factors in cancer states. | 1 |
5 | Cancer care providers should know that exercise have the potential to reduce body fats and cardiovascular risk factors in cancer states. | 1 |
6 | Cancer care providers should know that exercise had the potential to reduce the symptoms of anxiety, depression, and cognitive problems associated with cancer itself and anticancer therapies. Symptoms of depression were seen when kynurenine, which is a metabolite of tryptophan, crossed the blood-brain barrier. During exercise, PGC-1 | 2 |
7 | Cancer care providers should know that exercise improved muscle strength which was a powerful predictor of patient survival after surgery for cancers. | 1 |
8 | Cancer care providers should know that exercise had the potential to improve the potency and efficacy of anticancer drugs. | 2 |
9 | Cancer care providers should know that exercise had the potential to reduce the toxicity of anticancer drugs. | 2 |
10 | Cancer care providers should know that exercise improved blood flow; this might improve delivery of adequate concentrations of anticancer agents to tumors. | 1 |
11 | Cancer care providers should know that exercise improved recovery and reduced postoperative complications in patients undergoing surgery for solid tumors. | 1 |
12 | Cancer care providers should know that exercise could protect patients with and survivors of cancer from comorbidities. | 1 |
Following the two iterative Delphi rounds, consensus was not achieved on 4 (8.2%) of the 49 items presented to the panelists. These items remained equivocal, i.e., might be considered by educators, trainers, and/or regulatory bodies when designing training/educational intervention and/or continuing education to enrich knowledge and expand understanding of primary healthcare providers and CAM practitioners on how exercise might stimulate anticancer immunity and suppress cancerous cells or not depending on the individual needs of the trainers/educators, and/or regulatory bodies. These equivocal items are shown in Table
Items on which consensus was not achieved following the two iterative Delphi rounds.
First Delphi round | Second Delphi round | ||||
---|---|---|---|---|---|
# | Item | Median | IQR | Median | IQR |
1 | Cancer care providers should know that exercise interventions were unable to eradicate or significantly reduce already established tumors. | 5 | 3 | 6 | 3 |
2 | Cancer care providers should know that exercise might deplete reserves in the muscles and amino acids in the plasma. This might limit supply of energy to the immune cells. | 4 | 2 | 4 | 3 |
3 | Cancer care providers should know that exercise might increase production of free radicals, at least for short periods of time. This might promote tumors in genetically predisposed individuals. | 4 | 4 | 5 | 4 |
4 | Cancer care providers should know that exercise increased the need of antioxidant supplements. | 6 | 3 | 7 | 3 |
IQR: interquartile range.
In the present study, we sought for the first time formal consensus on important knowledge items that primary healthcare providers and CAM practitioners need to know on how exercise might stimulate anticancer immunity and suppress cancerous cells. Little guidance exists on what information and knowledge items should be included and discussed during a training/educational and/or continuing educational intervention designed to enrich knowledge and expand understanding of primary healthcare providers and CAM practitioners on how exercise might stimulate anticancer immunity and suppress cancerous cells [
In the present study, 45% of the researcher and experts contacted to rate and comment on the knowledge items responded and returned the questionnaire. Additionally, all invited healthcare providers and CAM practitioners responded and returned the questionnaire in the first Delphi round. In the second Delphi round, the vast majority of the panelists retuned the revised questionnaire. These high response rates add to the validity and strength of the present study. Although the sample size was comparatively small, researchers and experts who rated the knowledge items and commented on the knowledge items were of different backgrounds, had extensive experience in conducting research on the effects of exercise on stimulating anticancer immunity and suppressing cancerous cells, and had experience in caring for cancer patients and survivors. Moreover, the healthcare providers and CAM practitioners who participated in the Delphi rounds were of both genders, belonged to different age groups, were employed by the governmental and private sectors, had different degrees and specialties, and, more importantly, interacted with a considerable number of cancer patients and survivors over an extended years of experience in the field. Such diversity might add validity, strength, and suitability of considering the knowledge items that the panelists finally agreed upon by the end of the Delphi rounds by trainers, educators, and/or regulatory bodies at the time of designing training/educational intervention and/or continuing education for primary healthcare providers and CAM practitioners on the role of exercise in stimulating anticancer immunity and suppressing cancerous cells.
In this study, the panelists agreed that the cancer curricula of primary healthcare providers and CAM practitioners were deficient. Furthermore, the panelists agreed that more efforts were needed to increase knowledge of primary healthcare providers on how exercise might stimulate anticancer immunity and suppress cancerous cells. These finding were consistent with findings of other studies conducted elsewhere in the world [
Gold standards in considering what knowledge items trainers, educators, and/or regulatory bodies should consider at the time of designing training/educational intervention and/or continuing education for primary healthcare providers and CAM practitioners on the role of exercise in stimulating anticancer immunity and suppressing cancerous cells do not exist. Therefore, consensual core lists might serve as guidance for trainers, educators, and/or regulatory bodies while designing training/educational intervention and/or continuing education for primary healthcare providers and CAM practitioners on the role of exercise in stimulating anticancer immunity and suppressing cancerous cells. Using such consensual core lists might reduce bias, enhance transparency, impart validity, and add strength to judgmental methods while developing concepts [
Primary healthcare providers and CAM practitioners need to know all items presented in Table
Although exercise is generally safe and was shown to significantly improve clinical, functional, and survival outcomes in cancer patients, it is noteworthy mentioning that cancer patients and survivors are vulnerable populations who are at increased risk of morbidity and mortality due to the significant consequences of cancer and its therapy. Therefore, healthcare providers and CAM practitioners should be aware that a one-size-fits-all approach would not be practically feasible for all patients; rather, recommendations for exercise should be personalized to meet the physical and psychosocial needs of the patients and survivors [
In this study, 4 knowledge items remained equivocal following the second Delphi round. These items might be considered or not depending on the preference of trainers/educators at the time of designing training/educational interventions to increase the knowledge of primary health providers and CAM partitions on how exercise might stimulate anticancer immunity and suppress cancerous cells.
The results of the present study might be interpreted after considering the following limitations. First, the survey could have been conducted in one of the conferences on exercise and cancer. Such conferences could have gathered a large number of experts in the field. Second, we did not include patients and or survivors of cancer in the two iterative Delphi rounds. However, inclusion of patients and survivors could have influenced agreements and disagreements on the different statements. Inclusion of patients and survivors was hampered by the nature of the statements explaining molecular mechanisms on how exercise might stimulate anticancer immunity and suppress cancerous cells. Finding cancer patients and survivors with prior sufficient knowledge on how exercise might stimulate anticancer immunity and suppress cancerous cells was difficult. Third, the sample size of the panel was not large. However, the sample size used in this study was in the range of those used in previous studies in healthcare [
In this study, formal consensus was achieved for the first time on a core list of knowledge items on how exercise might stimulate anticancer immunity and suppress cancerous cells. This core list might be considered at the time of developing training/educational interventions and/or continuous education for primary healthcare providers and CAM practitioners. Future studies are still needed to investigate if such consensual lists might improve congruence in cancer care continuum and improve survival rates and wellbeing of cancer patients and survivors.
Data supporting the results reported in this published article can be found in the Results Section and as Supplementary Materials with this manuscript or by contacting the corresponding author.
The authors declare that there are no conflicts of interest.
The authors would like to thank all experts who took part in this study. An-Najah National University is thanked for granting permission to conduct the study. A part of this study was performed when Ramzi Shawahna was receiving support from a Zamala grant offered by Bank of Palestine, Association Welfare, and An-Najah National University.
Supplementary Table S1 provides potential effects of exercise on cancer and its therapy retrieved from the literature.