Perspectives of pediatric oncologists and palliative care physicians on the therapeutic use of cannabis in children with cancer

Abstract Background Children with cancer are increasingly using cannabis therapeutically. Aim The purpose of this study was to determine the perspectives and practices of pediatric oncologists and palliative care physicians regarding the use of cannabis for medical purposes among children with cancer. Methods A self‐administered, voluntary, cross‐sectional, deidentified online survey was sent to all pediatric oncologists and palliative care physicians in Canada between June and August 2020. Survey domains included education, knowledge, and concerns about cannabis, views on its effectiveness, and the importance of cannabis‐related research. Data were analyzed using descriptive statistics. Results In total, 122/259 (47.1%) physicians completed the survey. Although 62.2% of the physicians completed some form of training about medical cannabis, nearly all (95.8%) desired to know more about the dosing, side effects, and safety of cannabis. Physicians identified a potential role of cannabis in the management of nausea and vomiting (85.7%), chronic pain (72.3%), cachexia/poor appetite (67.2%), and anxiety or depression (42.9%). Only four (0.3%) physicians recognized cannabis to be potentially useful as an anticancer agent. Nearly all physicians reported that cannabis‐related research for symptom relief is essential (91.5%) in pediatric oncology, whereas 51.7% expressed that future studies are necessary to determine the anticancer effects of cannabis. Conclusions Our findings indicate that most pediatric oncologists and palliative care physicians recognize a potential role for cannabis in symptom control in children with cancer. Well‐conducted studies are required to create evidence for cannabis use and promote shared decision making with pediatric oncology patients and their caregivers.

(95.8%) desired to know more about the dosing, side effects, and safety of cannabis.
Physicians identified a potential role of cannabis in the management of nausea and vomiting (85.7%), chronic pain (72.3%), cachexia/poor appetite (67.2%), and anxiety or depression (42.9%). Only four (0.3%) physicians recognized cannabis to be potentially useful as an anticancer agent. Nearly all physicians reported that cannabisrelated research for symptom relief is essential (91.5%) in pediatric oncology, whereas 51.7% expressed that future studies are necessary to determine the anticancer effects of cannabis.
Conclusions: Our findings indicate that most pediatric oncologists and palliative care physicians recognize a potential role for cannabis in symptom control in children with cancer. Well-conducted studies are required to create evidence for cannabis use and promote shared decision making with pediatric oncology patients and their caregivers.

| INTRODUCTION
Cannabis products are derived from the plant Cannabis Sativa and are available in many forms, including dried flowers; hash; extracts, such as oil and shatter; and edibles. 1,2 Cannabis plant contains more than 100 compounds called phytocannabinoids, many of which are bioactive. 2 The two most prominent cannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). 3 Recent changes in cannabis legislation in Canada have made cannabis products more accessible and have raised public interest in using cannabis for medical purposes, including for children with cancer. 4 Outside of intractable epilepsy, minimal data exist on the therapeutic use of cannabis in children, despite its widespread use and interest. Several clinical trials have examined the therapeutic role of CBD for the treatment of seizures in children with Dravet syndrome, Lennox-Gastaut syndrome or tuberous sclerosis. [5][6][7][8] Overall, these trials demonstrated that CBD significantly reduced the frequency of seizures compared to placebo. 5,6,8 The majority of the adverse effects associated with CBD use were non-severe and included diarrhea, vomiting, fatigue, pyrexia, somnolence, and decreased appetite. 5,6,8 However, limited data exist on the use of cannabis for conditions outside of epilepsy. Despite limited evidence on the safety or efficacy of cannabis in pediatric oncology, parents or caregivers of children with cancer may use cannabis products for various indications, including nausea, vomiting, pain, lack of appetite, mood, and as an anticancer agent. [9][10][11] In a few recently published studies, children and young adults with cancer reported using cannabis products for nausea and vomiting, depressed mood, sleep disturbances, pain, poor appetite and weight loss. 9,10 In a study from Israel, nearly 80% of children and their parents, believed that cannabis alleviated their physical and psychological distress; however, the study used no control group, and outcomes were self-reported. 9 Pediatric oncologists are increasingly facing questions from patients and their caregivers regarding the role of cannabis for symptom control and treatment of cancer. Lack of evidence, concern for adverse psychiatric and cognitive effects, and dosing guidelines have generally limited physician support for using cannabis products in children. [12][13][14] In a recently conducted survey of interdisciplinary providers in pediatric oncology in the United States, 30% of providers received ≥1 request for cannabis in the previous month. 12 A nationwide survey of medical oncologists from the United States showed that despite insufficient information on cannabis, 80% of oncologists discussed and 46% recommended cannabis to their adult patients with cancer. 15 The results of these surveys, however, may not be directly applicable to the Canadian setting due to differences in the healthcare systems, medical cannabis access, and recent legalization of recreational cannabis throughout Canada. 16,17 Therefore, to understand perspectives concerning the therapeutic use of cannabis in Canadian children with cancer and determine the necessity for cannabis-related research, we surveyed pediatric oncologists and palliative care physicians in Canada.

| MATERIALS AND METHODS
We conducted a cross-sectional study using a self-administered, deidentified online survey. Pediatric oncologists, palliative care physicians, and fellows in both sub-specialties were eligible to participate in this study if they provided clinical care to oncology patients at a Canadian pediatric academic health sciences center. We convened a content expert panel of pediatric oncologists, pediatric palliative care physicians, pharmacologists, and researchers to develop this survey.
The specific survey domains were informed by discussion and consensus among the members of the expert panel. Survey domains included education and desired knowledge about medical cannabis, perspectives on the use of medical cannabis in pediatric oncology, concerns about the use of medical cannabis, and attitudes toward future research. We generated survey questions in each domain by reviewing published survey instruments 12,15 and discussing with the content expert panel. The survey was piloted with five pediatric oncologists and palliative care physicians to test flow, salience, appropriateness, ease of administration, and completion time. Following pilot testing, we modified the survey to enhance its flow, clarity, and response reliability. 18,19 The final survey included 21 items and required approximately 5-6 min to complete. The final survey instrument was translated into French and back-translated into English for accuracy and was offered in both official languages.

| Definitions
We defined cannabis use as authorized and nonauthorized use of any medical and non-medical cannabis product without any distinction between the use of THC or CBD products. Excluded from this survey were pharmaceutically derived nabiximols and synthetic THC analogs, dronabinol and nabilone. Regardless of how or where the cannabis was obtained, the intent had to be for medical purposes; physicians were to exclude considerations for recreational or accidental cannabis exposures.

| Geographic regions
Due to the smaller number of physicians in some provinces, we col- Territories, Nunavut, and Yukon were excluded due to the absence of academic pediatric health centers in these regions.

| Survey administration and dissemination
The survey was created in Research Electronic Data Capture (REDCap). 20 We prepared the list of the eligible physicians from the children oncology group website and by contacting the pediatric centers. All eligible participants received a personalized invitation and a link to the survey by email. We sent three reminders at 3-week intervals to non-responders. Survey completion was voluntary. Data were automatically entered into a deidentified REDCap database. Upon completing the survey, physicians could opt into a raffle to win one of five $100 e-gift cards; contact details for this purpose were not linkable to ensure the anonymity of the survey responses.

| Statistical analysis and ethics approval
We used frequency distribution to depict the frequency or count of the different variables in the data set. Data analysis was performed

| RESULTS
The survey was sent to 259 individuals. A total of 122 (47.1%) physicians completed questions about cannabis. Three participants were excluded because they did not meet the study inclusion criteria. The final study population included 119 participants. Overall, 79% were physicians, 21% were fellows, 50.4% were from Central Canada, 40.4% were from Western Canada, and 9.2% were from Eastern Canada.

| Education and desired knowledge about medical cannabis
In total, 62.2% of physicians reported completing formal or informal training, most commonly with peer-reviewed sources (70.5%) and at conferences or workshops (50.4%; Table S1). Many physicians indicated that other forms of training were preferable to conferences or workshops, including webinars or video lectures (64.7%), peer-  Table S2).  Not mutually exclusive. b Of the five participants reporting "other" concerns, four provided additional details: n = 1 cannabis-drug interactions; n = 1 cost of products and lack of insurance; n = 1 concern about long term side effects; n = 1 inability to assess subjective side effects).

| Perspectives on the use of medical cannabis
Most physicians (91.6%) provided care to at least one child with cancer using cannabis for symptom management within the last 6 months. Additionally, more than half (56.8%) had one patient in their clinical practice using cannabis as an adjuvant anticancer agent in the previous 6 months ( Possible harms Concerns about the harms associated with cannabis use "I worry patients with a good prognosis will get exposed and potentially lead to unnecessary addiction."

Financial burden
Financial concerns related to cannabis use "I think it would be very important to explore the cost/financial implications of cannabis therapy. It's hard to recommend a therapy when the cost is so prohibitive even it's for symptom management." absence of such policies, and the remainder (37.

| Perspectives on future research on the use of medical cannabis
Almost all physicians (91.5%) considered the conduct of studies investigating the role of cannabis in treating cancer-or cancer-related symptoms to be very important or important, and stated that they would likely enroll their patients in such a study (93.2%) (Figure 2). One-half of physicians (51.7%) also conveyed that it is crucial to conduct studies to determine the anticancer effects of cannabis; 47.9% of physicians expressed their desire to enroll their patients in such a study (Figure 2).

| DISCUSSION
In this first Canadian study investigating the perspectives and practices of pediatric oncologists and palliative care physicians regarding the use of cannabis for medical purposes among children with cancer, we found that most physicians provided care to children using medical cannabis, perceived the potential role of cannabis for symptom relief, wanted to learn more about medical cannabis, and considered cannabis-related research to be crucial. such as throat and abdomen pain. 9 In another qualitative study, adolescents and young adults with cancer, and their parents, endorsed cannabis to manage nausea, pain, and anorexia after weighing the risk of potential physiological and psychological side effects of cannabis. 27 The majority of physicians in our study also believed that cannabis has a role in symptom control, especially among children receiving palliative care. The physicians' perspectives likely symbolize the positive benefits observed in their clinical practice or their awareness of the emerging data on the benefits of cannabis for symptom control among children with cancer, especially in a palliative care setting where the risks associated with cannabis are low. [28][29][30] Although the above-mentioned observational studies signal the potential benefits of cannabis use in pediatric oncology, no robust clini-