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.

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.

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.

A Comprehensive Review of Cannabis in Patients with Cancer: Availability in the USA, General Efficacy, and Safety.

PURPOSE OF REVIEW: As the legalization of medical cannabis continues across the USA, oncology care providers will be increasingly asked to provide recommendations regarding its use in the cancer setting. In this article, we review recent literature that analyzes cannabis use specifically in patients with cancer and provide an accessible guide for clinicians, researchers, and patients. RECENT FINDINGS: We aimed to answer questions about the availability of cannabis in the USA, the trials supporting its use in the cancer setting, and the important factors to consider related to safety. Thirty states plus the District of Columbia have established comprehensive medical cannabis programs, each with different regulations and products available. In June 2018, Epidiolex, a cannabis extraction product containing 99% CBD, was approved to treat refractory seizures; however, whole-plant products and non-prescription extraction products dominate the market. Recent randomized, placebo-controlled studies of nabiximols (Sativex) in patients with refractory cancer-pain have largely shown no significant benefits. Conversely, large observational studies suggest patients with cancer using cannabis report significant improvement of many common symptoms. Cannabis use appears well tolerated, with few serious adverse effects reported. Though prospective clinical trials are needed to provide the robust data required to establish the proper role of cannabinoid and cannabis-based therapy in cancer patients, physicians can draw upon the knowledge currently available to have informed discussions with their patients.

Impact of opioid use on health care utilization and survival in patients with newly diagnosed stage IV malignancies.

PURPOSE: Patients with advanced cancers frequently experience pain. Opioids are commonly prescribed to treat cancer-related pain, but their use might be associated with undesirable consequences including adverse effects and tumor progression, resulting in increased heath care utilization and shorter survival. We examined these possibilities in a large cohort of patients diagnosed with ten common advanced malignancies. METHODS: We identified 1386 newly diagnosed patients with stage IV non-hematologic malignancies from 2005 to 2013 and ascertained opioid utilization within 90 days of starting anti-cancer treatment using electronic medical record and tumor registry data. Opioid utilization was stratified into low opioid (LO; < 5 mg oral morphine equivalents (OME)/day) and high opioid (HO; ≥ 5 mg OME/day). Health care utilization included tallies of emergency room, urgent care, and inpatient visits. The association of opioid use, tumor type prognosis, age, and gender with overall survival was analyzed in univariate and multivariate models. RESULTS: HO use patients (n = 624) had greater health care utilization compared to LO use patients (n = 762; p < 0.05). HO use patients also had shorter survival (median survival, 5.5 vs 12.4 months; p < 0.0001). On multivariate analysis, HO use remained associated with shorter overall survival (HR 1.4; 95% CI, 1.3-1.6; p < 0.0001) after adjusting for age, gender, and prognostic group. CONCLUSIONS: In advanced cancer patients, HO use is associated with greater health care utilization and shorter survival. Prospective studies using opioid-sparing approaches are indicated, to confirm these retrospective findings and to evaluate if these undesirable effects associated with opioid use can be mitigated.

A systematic review of the impact of pain on overall survival in patients with cancer.

PURPOSE: Pain commonly occurs in cancer patients, and has been associated with shorter survival. However, the importance of pain is less clear when analyzed with other known prognostic variables. This systematic review was performed to better understand how pain impacts overall survival (OS) in common cancers when key clinical variables are included in multivariate analysis. METHODS: A Medline search was completed to find studies examining the relationship between pain, clinical variables, and OS in patients with breast, colorectal, lung, or prostate cancer. Multivariate analysis included known prognostic variables including age, performance status, disease burden, and laboratory parameters. RESULTS: Fifty studies met inclusion criteria. In patients with breast, colorectal, and lung cancer, pain was not a significant prognostic factor for OS on multivariate analysis in most studies. In contrast, several studies suggest that pain is an independent prognostic factor for OS in advanced prostate cancer, even when relevant clinical prognostic variables are included. However, analgesic use was often used as a surrogate for prostate cancer pain, making it difficult to determine whether pain or opioid exposure was more important in influencing survival. CONCLUSIONS: Pain may be associated with shorter survival in patients with cancer, but the mechanism for this relationship is unknown. The available evidence is insufficient to definitively determine if pain independently influences survival in patients with breast, colorectal, or lung cancer. The majority of studies in prostate cancer show pain to be an independent prognostic factor for OS, and often also incorporate opioid analgesic use in multivariate analysis. Prospective studies are needed to better understand how opioid utilization and pain may affect cancer progression and survival in diverse malignancies.

Data quality in a survey of registered medical cannabis users with cancer: nonresponse and measurement error.

Cannabis use among individuals with cancer is best understood using survey self-report. As cannabis remains federally illegal, surveys could be subject to nonresponse and measurement issues impacting data quality. We surveyed individuals using medical cannabis for a cancer-related condition in the Minnesota Medical Cannabis Program (MCP). Although survey responders are older, there are no differences by race and ethnicity, gender, or receipt of reduced cannabis registry enrollment fee. Responders made a more recent purchase and more recently completed an independent symptom assessment for the registry than nonresponders, suggesting some opportunity for nonresponse error. Among responders, self-report and MCP administrative data with respect to age, race, gender, registry certification, and cannabis purchase history were similar. Responders were less likely to report receipt of Medicaid than would be expected based on registry low-income enrollment eligibility. Although attention should be paid to potential for nonresponse error, surveys are a reliable tool to ascertain cannabis behavior patterns in this population.

Effective Strategies for the Prevention and Mitigation of Phosphatidylinositol-3-Kinase Inhibitor-Associated Hyperglycemia: Optimizing Patient Care.

Hyperglycemia is a common adverse event (AE) associated with phosphatidylinositol-3-kinase inhibitors (PI3Kis) and considered an on-target effect. Presence of hyperglycemia is associated with poor outcomes in patients with cancer, and there is need for further refinement of hyperglycemia prevention and mitigation strategies in patients receiving PI3Kis. In this review, the authors highlight effective strategies for preventing PI3Ki-induced hyperglycemia before and during treatment as well as hyperglycemia management. Prior to initiating treatment with PI3Ki, identify baseline risk factors of patients at increased risk for developing hyperglycemia, which include older age, obesity, and glycosylated hemoglobin (HbA1c) 5.7%-6.4% (prediabetes or Type 2 diabetes). To prevent new-onset hyperglycemia, optimize blood glucose, and recommend a low-carbohydrate (60-130 g/day) diet along with regular exercise to all patients prior to initiating the PI3Ki. Prophylactic metformin may be considered in all patients starting a PI3Ki with HbA1c ≤6.4%. Although existing recommendations support monitoring fasting blood glucose (FBG) once weekly (twice-weekly for intermediate-risk, daily for high-risk patients) and HbA1c every 3 months upon initiation of PI3Ki, more frequent FBG monitoring may be considered for prompt detection of hyperglycemia. Experts also recommend considering postprandial glucose monitoring because it is an early indicator of glucose intolerance. If hyperglycemia develops, metformin (first-line) and/or sodium glucose co-transporter 2 inhibitors or thiazolidinediones (second-/third-line) are the preferred agents; consider early referral to an endocrinologist. In conclusion, hyperglycemia is a common but manageable AE associated with PI3Kis. Multidisciplinary approach to the prevention, monitoring, and management of hyperglycemia optimizes patient care and allows patients to maintain therapy on PI3Ki.

Perceptions, prevalence, and patterns of cannabis use among cancer patients treated at 12 NCI-Designated Cancer Centers.

BACKGROUND: The legal climate for cannabis use has dramatically changed with an increasing number of states passing legislation legalizing access for medical and recreational use. Among cancer patients, cannabis is often used to ameliorate adverse effects of cancer treatment. Data are limited on the extent and type of use among cancer patients during treatment and the perceived benefits and harms. This multicenter survey was conducted to assess the use of cannabis among cancer patients residing in states with varied legal access to cannabis. METHODS: A total of 12 NCI-Designated Cancer Centers, across states with varied cannabis-access legal status, conducted surveys with a core questionnaire to assess cannabis use among recently diagnosed cancer patients. Data were collected between September 2021 and August 2023 and pooled across 12 cancer centers. Frequencies and 95% confidence intervals for core survey measures were calculated, and weighted estimates are presented for the 10 sites that drew probability samples. RESULTS: Overall reported cannabis use since cancer diagnosis among survey respondents was 32.9% (weighted), which varied slightly by state legalization status. The most common perceived benefits of use were for pain, sleep, stress and anxiety, and treatment side effects. Reported perceived risks were less common and included inability to drive, difficulty concentrating, lung damage, addiction, and impact on employment. A majority reported feeling comfortable speaking to health-care providers though, overall, only 21.5% reported having done so. Among those who used cannabis since diagnosis, the most common modes were eating in food, smoking, and pills or tinctures, and the most common reasons were for sleep disturbance, followed by pain and stress and anxiety with 60%-68% reporting improved symptoms with use. CONCLUSION: This geographically diverse survey demonstrates that patients use cannabis regardless of its legal status. Addressing knowledge gaps concerning benefits and harms of cannabis use during cancer treatment is critical to enhance patient-provider communication.

Opioid requirement, opioid receptor expression, and clinical outcomes in patients with advanced prostate cancer.

BACKGROUND: Preclinical studies show that opioids stimulate angiogenesis and tumor progression through the mu opioid receptor (MOR). Although MOR is overexpressed in several human malignancies, the effect of chronic opioid requirement on cancer progression or survival has not been examined in humans. METHODS: We performed a retrospective analysis on 113 patients identified in the Minneapolis VA Tumor Registry (test cohort) and 480 patients from the national VA Central Cancer Registry (validation cohort) who had been diagnosed with stage IV prostate cancer between 1995 and 2010 to examine whether MOR expression or opioid requirement is associated with disease progression and survival. All opioids were converted to oral morphine equivalents for comparison. Laser scanning confocal microscopy was used to analyze MOR immunoreactivity in prostate cancer biopsies. The effects of variables on outcomes were analyzed in univariable and multivariable models. RESULTS: In patients with metastatic prostate cancer, MOR expression and opioid requirement were independently associated with inferior progression-free survival (hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.33-2.07, P<.001 and HR 1.08, 95% CI 1.03-1.13, P<.001, respectively) and overall survival (HR 1.55, 95% CI 1.20-1.99, P<.001 and HR 1.05, 95% CI 1.00-1.10, P = .031, respectively). The validation cohort confirmed that increasing opioid requirement was associated with worse overall survival (HR 1.005, 95% CI 1.002-1.008, P = .001). CONCLUSION: Higher MOR expression and greater opioid requirement are associated with shorter progression-free survival and overall survival in patients with metastatic prostate cancer. Nevertheless, clinical practice should not be changed until prospective randomized trials show that opioid use is associated with inferior clinical outcomes, and that abrogation of the peripheral activities of opioids ameliorates this effect.

Pneumococcal pyomyositis: report of 2 cases and review of the literature.

Streptococcus pneumoniae is an uncommon cause of pyomyositis. It is unclear whether the clinical presentation and outcome of pneumococcal pyomyositis differ depending on the host's underlying immune status. We describe 2 patients with pneumococcal pyomyositis, review all published cases, and compare characteristics between apparently healthy hosts and at-risk hosts. A total of 35 cases of pneumococcal pyomyositis were identified, 11 in apparently healthy hosts and 24 in at-risk hosts. Two-thirds of the patients had an antecedent respiratory illness or meningitis. At-risk hosts tended to have a longer interval between the development of symptomatic muscle infection and the diagnosis of pyomyositis and a significantly higher risk of disseminated disease at presentation, as manifested by involvement of multiple noncontiguous muscles or presence of meningitis. Overall, other than 1 death, all patients recovered with antibiotics and surgical drainage, but as might be expected there was a significantly higher rate of complications among at-risk hosts.

Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an American College of Physicians Clinical Practice Guideline.

BACKGROUND: Venous thromboembolism prophylaxis has been recommended for nonsurgical patients, but its effectiveness remains uncertain. PURPOSE: To assess the benefits and harms of prophylaxis in hospitalized adult medical patients and those with acute stroke. DATA SOURCES: MEDLINE and the Cochrane Library from 1950 through April 2011, reference lists, and study authors. STUDY SELECTION: English-language randomized trials were included if they provided clinical outcomes and evaluated therapy with low-dose heparin or related agents or mechanical measures compared with placebo, no treatment, or other active prophylaxis in the target population. DATA EXTRACTION: Two independent investigators extracted data on study characteristics and clinical outcomes up to 120 days after randomization. The primary outcome was total mortality. DATA SYNTHESIS: In medical patients, heparin prophylaxis did not reduce total mortality but did result in fewer pulmonary embolisms (PEs) (odds ratio [OR], 0.69 [95% CI, 0.52 to 0.90], but with evidence of publication bias) and an increase in all bleeding events (risk ratio [RR], 1.34 [CI, 1.08 to 1.66]). Heparin prophylaxis had no statistically significant effect on any outcome in patients with acute stroke except for an increase in major bleeding events (OR, 1.66 [CI, 1.20 to 2.28]). When trials of medical patients and those with stroke were considered together (18 studies; 36,122 patients), heparin prophylaxis reduced the incidence of PE (OR, 0.70 [CI, 0.56 to 0.87]; absolute reduction, 3 events per 1000 patients treated [CI, 1 to 5 events]) but increased the incidence of all bleeding (RR, 1.28 [CI, 1.05 to 1.56]) and major bleeding events (OR, 1.61 [CI, 1.23 to 2.10]), with an absolute increase of 9 bleeding events per 1000 patients treated (CI, 2 to 18 events), 4 of which were major (CI, 1 to 7 events). A reduction in total mortality approached statistical significance (RR, 0.93 [CI, 0.86 to 1.00]; P = 0.056; absolute decrease, 6 deaths per 1000 patients treated [CI, 0 to 11 deaths]). No statistically significant differences in clinical outcomes were observed in the 14 trials that compared unfractionated heparin with low-molecular-weight heparin. No improvements in clinical outcomes were seen in the 3 studies of mechanical prophylaxis in patients with stroke, but more patients had lower-extremity skin damage (RR, 4.02 [CI, 2.34 to 6.91])-an increase of 39 events per 1000 patients treated (CI, 17 to 77 events). LIMITATION: Non-English-language studies were not included, but these were few and small. CONCLUSION: Heparin prophylaxis had no significant effect on mortality, may have reduced PE in medical patients and all patients combined, and led to more bleeding and major bleeding events, thus resulting in little or no net benefit. No differences in benefits or harms were found according to type of heparin used. Mechanical prophylaxis provided no benefit and resulted in clinically important harm to patients with stroke. PRIMARY FUNDING SOURCE: American College of Physicians.

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.

Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216).

PURPOSE: Orteronel (TAK-700) is a nonsteroidal 17,20-lyase inhibitor suppressing androgen synthesis. We evaluated the clinical benefit of orteronel when added to androgen deprivation therapy (ADT) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer. METHODS: In this open-label randomized phase III study, patients with metastatic hormone-sensitive prostate cancer were randomly assigned 1:1 to ADT with orteronel (300 mg oral twice daily; experimental arm) or ADT with bicalutamide (50 mg oral once daily; control arm). The primary objective was the comparison of overall survival (OS), targeting a 33% improvement in median survival. A stratified log-rank test with a one-sided P ≤ .022 would indicate statistical significance. Secondary end points were progression-free survival (PFS), prostate-specific antigen (PSA) level at 7 months (≤ 0.2 v 0.2 to ≤ 4 v > 4 ng/mL), and adverse event profile. RESULTS: Among 1,279 patients included in the analysis, 638 were randomly assigned to the ADT plus orteronel arm and 641 to the control arm. The median age was 68 years; 49% had extensive disease. After a median follow-up of 4.9 years, there was a significant improvement in PFS (median 47.6 v 23.0 months, hazard ratio 0.58; 95% CI, 0.51 to 0.67; P < .0001) and PSA response at 7 months (P < .0001), but not in OS (median 81.1 v 70.2 months, hazard ratio 0.86; 95% CI, 0.72 to 1.02; P = .040, one-sided). More grade 3/4 adverse events occurred in the experimental versus the control arms (43% v 14%). Postprotocol life-prolonging therapy was received by 77.4% of patients in the control arm and 61.3% of patients in the orteronel arm. CONCLUSION: The study did not meet the primary end point of improved OS with orteronel. The lack of correlation of PFS and PSA response with OS raises concerns over assumption of their consistent surrogacy for OS in the context of extensive postprotocol therapy in this setting.

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.

Multisite, Randomized Trial of Early Integrated Palliative and Oncology Care in Patients with Advanced Lung and Gastrointestinal Cancer: Alliance A221303.

Background: We conducted a multicenter, randomized trial of early integrated palliative and oncology care in patients with advanced cancer to confirm the benefits of early palliative care (PC) seen in prior single-center studies. Methods: We randomly assigned patients with newly diagnosed incurable cancer to early integrated palliative and oncology care (n = 195) or usual oncology care (n = 196) at sites through the Alliance for Clinical Trials in Oncology. Patients assigned to the intervention were expected to meet with a PC clinician at least monthly until death, whereas usual care patients consulted PC on request. The primary endpoint was the change in quality of life from baseline to week 12 per the Functional Assessment of Cancer Therapy-General (FACT-G). Secondary outcomes included anxiety, depression, and communication about prognosis and end-of-life care. Results: Due to significant morbidity and a high proportion of measures that were not completed within the protocol window or for unknown reasons, the rate of missing data was high. We anticipated that 70% of patients (n = 280) would complete the FACT-G at baseline and week 12, but only 49.3% (n = 193/391) completed the measure. Delivery of the intervention was also suboptimal, as 14.9% (n = 29/195) of intervention patients had no PC visits by week 12. Intervention patients reported a mean 3.35 (standard deviation [SD] = 14.7) increase in FACT-G scores from baseline to week 12 compared with usual care patients who reported a 0.12 (SD = 12.7) increase from baseline (p = 0.10). Conclusion: This study highlights the difficulties of conducting multicenter trials of supportive care interventions in patients with advanced cancer. Clinical Trials Registration: NCT02349412.

Performance Measures Based on How Adults With Cancer Feel and Function: Stakeholder Recommendations and Feasibility Testing in Six Cancer Centers.

PURPOSE: Patient-reported outcome measures (PROMs) that assess how patients feel and function have potential for evaluating quality of care. Stakeholder recommendations for PRO-based performance measures (PMs) were elicited, and feasibility testing was conducted at six cancer centers. METHODS: Interviews were conducted with 124 stakeholders to determine priority symptoms and risk adjustment variables for PRO-PMs and perceived acceptability. Stakeholders included patients and advocates, caregivers, clinicians, administrators, and thought leaders. Feasibility testing was conducted in six cancer centers. Patients completed PROMs at home 5-15 days into a chemotherapy cycle. Feasibility was operationalized as ≥ 75% completed PROMs and ≥ 75% patient acceptability. RESULTS: Stakeholder priority PRO-PMs for systemic therapy were GI symptoms (diarrhea, constipation, nausea, vomiting), depression/anxiety, pain, insomnia, fatigue, dyspnea, physical function, and neuropathy. Recommended risk adjusters included demographics, insurance type, cancer type, comorbidities, emetic risk, and difficulty paying bills. In feasibility testing, 653 patients enrolled (approximately 110 per site), and 607 (93%) completed PROMs, which indicated high feasibility for home collection. The majority of patients (470 of 607; 77%) completed PROMs without a reminder call, and 137 (23%) of 607 completed them after a reminder call. Most patients (72%) completed PROMs through web, 17% paper, or 2% interactive voice response (automated call that verbally asked patient questions). For acceptability, > 95% of patients found PROM items to be easy to understand and complete. CONCLUSION: Clinicians, patients, and other stakeholders agree that PMs that are based on how patients feel and function would be an important addition to quality measurement. This study also shows that PRO-PMs can be feasibly captured at home during systemic therapy and are acceptable to patients. PRO-PMs may add value to the portfolio of PMs as oncology transitions from fee-for-service payment models to performance-based care that emphasizes outcome measures.

Impact of diabetes and hyperglycemia on health care utilization, infection risk, and survival in patients with cancer receiving glucocorticoids with chemotherapy.

BACKGROUND: Glucocorticoids are commonly used in chemotherapy regimens and may lead to hyperglycemia and increased infection rates. METHODS: We performed a retrospective analysis on 1781 patients who received intravenous chemotherapy with glucocorticoids between 2010 and 2015. Data was obtained using electronic medical record, billing modules, and tumor registry. We compared new infections and survival between patients with and without diabetes, after adjusting for demographic and cancer-related variables. RESULTS: In the first 12 months following chemotherapy, patients with diabetes (n = 330) had higher rates of hospital admissions (70.9% vs 57.4%), more infection-related admissions (37.0% vs 29.2%), and increased rates of new infections (61.2% vs 49.2%) when compared to patients without diabetes (n = 1451). One-year survival was worse among patients with diabetes (67.3% vs 78.3%), and in patients with at least one elevated glucose following chemotherapy (60.8% vs 78.5). After adjusting for cancer stage, age, and gender, diabetes history increased the odds of dying within one year after diagnosis by 86% (OR 1.86, 95% CI (1.37-2.52)) and of new infections by 68% (OR 1.68, 95% CI (1.26-2.24)). CONCLUSIONS: Among patients with cancer receiving intravenous chemotherapy with glucocorticoids we demonstrate those with diabetes have more hospital admissions, increased rates of infections, and worse survival.

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.