Effect of Electronic Symptom Monitoring on Patient-Reported Outcomes Among Patients With Metastatic Cancer: A Randomized Clinical Trial.

Importance: Electronic systems that facilitate patient-reported outcome (PRO) surveys for patients with cancer may detect symptoms early and prompt clinicians to intervene. Objective: To evaluate whether electronic symptom monitoring during cancer treatment confers benefits on quality-of-life outcomes. Design, Setting, and Participants: Report of secondary outcomes from the PRO-TECT (Alliance AFT-39) cluster randomized trial in 52 US community oncology practices randomized to electronic symptom monitoring with PRO surveys or usual care. Between October 2017 and March 2020, 1191 adults being treated for metastatic cancer were enrolled, with last follow-up on May 17, 2021. Interventions: In the PRO group, participants (n = 593) were asked to complete weekly surveys via an internet-based or automated telephone system for up to 1 year. Severe or worsening symptoms triggered care team alerts. The control group (n = 598) received usual care. Main Outcomes and Measures: The 3 prespecified secondary outcomes were physical function, symptom control, and health-related quality of life (HRQOL) at 3 months, measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference [MCID], 2-7 for physical function; no MCID defined for symptom control or HRQOL). Results on the primary outcome, overall survival, are not yet available. Results: Among 52 practices, 1191 patients were included (mean age, 62.2 years; 694 [58.3%] women); 1066 (89.5%) completed 3-month follow-up. Compared with usual care, mean changes on the QLQ-C30 from baseline to 3 months were significantly improved in the PRO group for physical function (PRO, from 74.27 to 75.81 points; control, from 73.54 to 72.61 points; mean difference, 2.47 [95% CI, 0.41-4.53]; P = .02), symptom control (PRO, from 77.67 to 80.03 points; control, from 76.75 to 76.55 points; mean difference, 2.56 [95% CI, 0.95-4.17]; P = .002), and HRQOL (PRO, from 78.11 to 80.03 points; control, from 77.00 to 76.50 points; mean difference, 2.43 [95% CI, 0.90-3.96]; P = .002). Patients in the PRO group had significantly greater odds of experiencing clinically meaningful benefits vs usual care for physical function (7.7% more with improvements of ≥5 points and 6.1% fewer with worsening of ≥5 points; odds ratio [OR], 1.35 [95% CI, 1.08-1.70]; P = .009), symptom control (8.6% and 7.5%, respectively; OR, 1.50 [95% CI, 1.15-1.95]; P = .003), and HRQOL (8.5% and 4.9%, respectively; OR, 1.41 [95% CI, 1.10-1.81]; P = .006). Conclusions and Relevance: In this report of secondary outcomes from a randomized clinical trial of adults receiving cancer treatment, use of weekly electronic PRO surveys to monitor symptoms, compared with usual care, resulted in statistically significant improvements in physical function, symptom control, and HRQOL at 3 months, with mean improvements of approximately 2.5 points on a 0- to 100-point scale. These findings should be interpreted provisionally pending results of the primary outcome of overall survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03249090.

Cannabis as an Anticancer Agent: A Review of Clinical Data and Assessment of Case Reports.

Background: Pre-clinical studies have demonstrated the potential anticancer activity of cannabinoids, yet little clinical data exist to support this. Nearly 40% of patients with cancer using cannabis believe it will treat their cancer with numerous anecdotal reports shared online through social media platforms. Case reports have been published in peer-reviewed journals, but often lack key clinical information to validate anticancer claims. Methods: We reviewed literature in PubMed and EBSCO databases that evaluated the relationship between cannabis or the endocannabinoid system and potential anticancer activity. We also reviewed online sources, books, and ClinicalTrials.gov for reports or studies on using cannabis as cancer treatment. All case reports published in peer-reviewed journals were compiled and appraised as weak, moderate, or strong based on the quality of evidence provided supporting an anticancer effect. Strong reports met three criteria; (a) active cancer at time of cannabis administration, (b) validated laboratory or radiographic responses were reported, and (c) cannabis used without concurrent anticancer treatments. Results: Of the 207 pre-clinical articles reviewed, 107 (52%) were pre-clinical studies with original data. A total of 77 unique case reports described patients with various cancers (breast, central nervous system, gynecological, leukemia, lung, prostate, and pancreatic) using cannabis. Our appraisal showed 14% of the case reports were considered strong, 5% moderate, and the remaining 81% were weak. Ten percent of cases were in pediatric patients. Cannabidiol use was most often reported as the anticancer cannabinoid with daily doses ranging from 10 to 800 mg. Tetrahydrocannabinol use was reported in six studies, with doses ranging from 4.8 to 7.5 mg. Two small trials published data on survival in patients with recurrent glioblastoma multiforme. Conclusion: This review of clinical data suggests most published, peer-reviewed case reports provide insufficient data to support the claim for cannabis as an anticancer agent, and should not be used in place of evidence-based, traditional treatments outside of a clinical trial. No strong clinical trial data exist to confirm the pre-clinical studies that suggest cannabinoids may have an anticancer benefit. Future studies exploring anticancer potential of cannabis in patients with metastatic cancers who have not responded to traditional therapy are needed.

A randomized trial of medical cannabis in patients with stage IV cancers to assess feasibility, dose requirements, impact on pain and opioid use, safety, and overall patient satisfaction.

PURPOSE: The prevalence of medical cannabis (MC) use in patients with cancer is growing, but questions about safety, efficacy, and dosing remain. Conducting randomized, controlled trials (RCTs) using state-sponsored MC programs is novel and could provide data needed to guide patients and providers. METHODS: A pilot RCT of patients with stage IV cancer requiring opioids was conducted. Thirty patients were randomized 1:1 to early cannabis (EC, n = 15) versus delayed start cannabis (DC, n = 15). The EC group obtained 3 months (3 M) of MC through a state program at no charge, while the DC group received standard oncology care without MC for the first 3 M. Patients met with licensed pharmacists at one of two MC dispensaries to determine a suggested MC dosing, formulation, and route. Patients completed surveys on pain levels, opioid/MC use, side effects, and overall satisfaction with the study. RESULTS: Interest in the study was high as 36% of patients who met eligibility criteria ultimately enrolled. The estimated mean daily THC and CBD allotments at 3 M were 34 mg and 17 mg, respectively. A higher proportion of EC patients achieved a reduction in opioid use and improved pain control. No serious safety issues were reported, and patients reported high satisfaction. CONCLUSION: Conducting RCTs using a state cannabis program is feasible. The addition of MC to standard oncology care was well-tolerated and may lead to improved pain control and lower opioid requirements. Conducting larger RCTs with MC in state-sponsored programs may guide oncology providers on how to safely and effectively incorporate MC for interested patients.

Impact of Pain, Opioids, and the Mu-opioid Receptor on Progression and Survival in Patients With Newly Diagnosed Stage IV Pancreatic Cancer.

OBJECTIVES: Pancreatic adenocarcinoma is frequently associated with pain requiring opioid therapy. Opioids, however, have been implicated in causing tumor progression, ultimately shortening survival. We examined the impact of pain, opioid use, and the mu-opioid receptor (MOP-R) expression in tumor tissue on progression-free survival and overall survival of patients with metastatic pancreatic cancer. METHODS: We identified 103 patients with metastatic pancreatic adenocarcinoma receiving chemotherapy and abstracted data from Tumor Registry, in addition to pain, opioid exposure, carbohydrate antigen 19-9 values, survival, and imaging response. MOP-R expression was evaluated using an immunohistochemistry assay. The association of variables with progression-free survival and overall survival was analyzed in univariate and multivariate models. RESULTS: Patients with low opioid use (<5 mg oral morphine equivalent/d) survived longer than patients with high opioid (HO) use (≥5 mg oral morphine equivalent/d) (median overall survival of 315 vs. 150 d; hazard ratio [HR]=1.79; 95% confidence interval [CI]: 1.13, 2.84). This effect persisted on multivariate models (adjusted HR=2.76; 95% CI: 1.39, 5.48). Low opioid patients tended to respond better to treatment than HO patients, based on carbohydrate antigen 19-9. Patients with low MOP-R expression had longer median survival (230 vs. 193 d), though the HR was not significant (1.15; 95% CI: 0.71, 1.88). Baseline pain was not associated with outcomes. CONCLUSION: In patients with metastatic pancreatic adenocarcinoma, HO use is associated with decreased survival, but the severity of baseline pain and MOP-R expression score in tumor tissue does not correlate with clinical outcomes.

Collection of electronic patient-reported symptoms in patients with advanced cancer using Epic MyChart surveys.

BACKGROUND: Use of electronic patient-reported outcomes (ePROs) in routine cancer care can help identify troublesome symptoms and facilitate discussions between patients and clinicians and has been shown to improve patient satisfaction, quality of life, and survival. METHODS: Eighty patients with stage IV non-hematologic malignancies on chemotherapy participated. Patient-Reported Symptom Monitoring (PRSM) surveys were sent every 14 days via the Epic MyChart system over a 12-week period. Surveys were offered via phone or paper if patients failed to complete the automated MyChart survey by day 16. Severe symptoms or concerning symptom trends were automatically highlighted in reports for clinic staff. Patients reporting severe symptoms were routed to oncology nursing triage for standard symptom care management. RESULTS: Two hundred seventy-one surveys were sent during the 12-week study period. One hundred eighty-three surveys (66%) were completed, with 68% completed electronically via MyChart, 25% by paper, and 7% by phone call from a research coordinator. At least one severe symptom was reported on 36% of all surveys. However, most severe symptoms did not result in urgent triage follow-up because they were already being addressed and/or patients felt they were manageable. Patients and clinicians generally said the ePRO was efficient and helpful for addressing distressing symptoms and would use it in routine oncology care. CONCLUSION: ePROs can be integrated into the electronic health record using the Epic MyChart system. Patients and clinicians gave positive feedback on the system. Monitoring symptoms in real time may soon become part of standard oncology practice and requires seamless methods for collection.

Impact of Medical Cannabis on Patient-Reported Symptoms for Patients With Cancer Enrolled in Minnesota's Medical Cannabis Program.

PURPOSE: Minnesota's medical cannabis program is unique, in that it routinely collects patient-reported scores on symptoms. This article focuses on changes in symptom severity reported by patients with cancer during their first 4 months of program participation. MATERIALS AND METHODS: Patients with cancer in Minnesota's medical cannabis program reported symptoms (anxiety, lack of appetite, depression, disturbed sleep, fatigue, nausea, pain, and vomiting) at their worst over the last 24 hours before each medical cannabis purchase. Baseline scores on each of the eight symptoms were statistically compared with the average symptom scores reported in the first 4 months of program participation. Symptom scores were also calculated as percent change from baseline, with patients achieving and maintaining at least a 30% reduction in symptoms reported in this article. Patients also reported intensity of adverse effects. RESULTS: A significant reduction in scores was found across all symptoms when comparing baseline scores with the average score submitted within the first 4 months of program participation (all Ps < .001). The proportion of patients achieving 30% or greater symptom reduction within the first 4 months of program participation varied from 27% (fatigue) to 50% (vomiting), with a smaller proportion both achieving and maintaining those improvements. Adverse effects were reported in a small proportion of patients (10.5%). CONCLUSION: Patients with cancer enrolled in Minnesota's medical cannabis program showed significant reduction across all eight symptoms assessed within 4 months of program participation. Medical cannabis was well tolerated, and some patients attained clinically meaningful and lasting levels of improvement.