Should Cannabis be Used for Anorexia in Patients With Cancer?

Healthcare professionals are frequently asked about the benefits of cannabis for appetite or anorexia-cachexia syndrome. In popular culture, cannabis has a reputation of causing an increased hunger, slang termed "the munchies," so many patients consume this with the hope that it may improve the loss of appetite associated with serious illness such as cancer. There have only been a few randomized, controlled trials studying the controversial question as to if cannabis improves appetite. These studies are small and show no statistically significant benefit for appetite and one small study showed improvement of taste for foods. Due to regulation barriers, the studies have use synthetic products, not the products that represent what is more commonly used in the population, often whole flower smoked, vaporized or oral products. Despite the popularity of cannabis in culture, often touted as a panacea for all maladies, the evidence and education for several adverse effects and potential drug interactions have has yet to catch up with the cultural craze. International cannabis experts in the United States and Australia do not routinely certify patients for medical cannabis off trial for anorexia-cachexia, but one expert in Canada would consider use in selected cancer patients.

Supporting gut health with medicinal cannabis in people with advanced cancer: potential benefits and challenges.

The side effects of cancer therapy continue to cause significant health and cost burden to the patient, their friends and family, and governments. A major barrier in the way in which these side effects are managed is the highly siloed mentality that results in a fragmented approach to symptom control. Increasingly, it is appreciated that many symptoms are manifestations of common underlying pathobiology, with changes in the gastrointestinal environment a key driver for many symptom sequelae. Breakdown of the mucosal barrier (mucositis) is a common and early side effect of many anti-cancer agents, known to contribute (in part) to a range of highly burdensome symptoms such as diarrhoea, nausea, vomiting, infection, malnutrition, fatigue, depression, and insomnia. Here, we outline a rationale for how, based on its already documented effects on the gastrointestinal microenvironment, medicinal cannabis could be used to control mucositis and prevent the constellation of symptoms with which it is associated. We will provide a brief update on the current state of evidence on medicinal cannabis in cancer care and outline the potential benefits (and challenges) of using medicinal cannabis during active cancer therapy.

Radiation Therapy in the Last Month of Life: Association With Aggressive Care at the End of Life.

CONTEXT: Half of the patients with cancer who undergo radiation therapy do so with palliative intent. OBJECTIVES: To determine the proportion of undergoing radiation in the last month of life, patient characteristics, cancer course, the type and duration of radiation, whether palliative care was involved, and the of radiation with aggressive cancer care metrics. METHODS: One thousand seven hundred twenty-seven patients who died of cancer between January 1, 2018, and December 31, 2019, were included. Demographics, cancer stage, palliative care referral, advance directives, use of home health care, radiation timing, and survival were collected. Type of radiation, course, and intent were reviewed. Chi-square analysis was utilized for categorical variables, and Kruskal-Wallis tests for continuous variables. A stepwise selection was used to build a Cox proportional hazard model. RESULTS: Two hundred thirty-three patients underwent radiation in the last month of life. Younger patients underwent radiation 67.3 years (SD 11.52) versus 69.2 years (SD 11.96). 42.6% had radiation within two weeks of death. The average fraction number was 5.5. Individuals undergoing radiation were more likely to start chemotherapy within the last 30 days of life, continue chemotherapy within two weeks of death, be admitted to the ICU, and have two or more hospitalizations or emergency room visits. Survival measured from the date of diagnosis was shorter for those undergoing radiation, 122 days (IQR 58-462) versus 474 days (IQR 225-1150). Palliative care consultations occurred later in those undergoing radiation therapy. CONCLUSION: Radiation therapy in the last month of life occurs in younger patients with rapidly progressive cancer, who are subject to more aggressive cancer care, and have late palliative care consults.

Should Buprenorphine Be Considered a First-Line Opioid for the Treatment of Moderate to Severe Cancer Pain?

Cancer pain remains a significant problem worldwide, affecting more than half of patients receiving anti-cancer treatment and most patients with advanced disease. Opioids remain the cornerstone of therapy, and morphine, given its availability, multiple formulations, price, and evidence base, is typically considered the first-line treatment for moderate to severe cancer pain. Buprenorphine has emerged in recent decades as an alternative opioid for treating chronic pain and substance use disorder (SUD). However, it remains controversial whether buprenorphine should be considered a first-line opioid for moderate to severe cancer pain. In this "Controversies in Palliative Care" article, three expert clinicians independently answer this question. Specifically, each group provides a synopsis of the key studies that inform their thought process, share practical advice on their clinical approach, and highlight the opportunities for future research. All three groups agree that there is a place for the use of buprenorphine as a first-line opioid in cancer pain. Specifically, they mention populations of elderly patients, patients with renal failure, and those with (SUD). They also underscore many unique and favorable characteristics of buprenorphine, such as the low risk for respiratory depression, lack of adverse effects on testosterone levels in men, no risk of serotonin syndrome when combined with antidepressants, and ease of use given its transdermal, transmucosal, and sublingual formulations. However, further studies are needed to guide the use of buprenorphine for cancer pain-primarily randomized clinical trials (RCTs) comparing buprenorphine with other opioids in various pain syndromes.

MASCC guideline: cannabis for cancer-related pain and risk of harms and adverse events.

BACKGROUND: Approximately 18% of patients with cancer use cannabis at one time as palliation or treatment for their cancer. We performed a systematic review of randomized cannabis cancer trials to establish a guideline for its use in pain and to summarize the risk of harm and adverse events when used for any indication in cancer patients. METHODS: A systematic review of randomized trials with or without meta-analysis was carried out from MEDLINE, CCTR, Embase, and PsychINFO. The search involved randomized trials of cannabis in cancer patients. The search ended on November 12, 2021. The Jadad grading system was used for grading quality. Inclusion criteria for articles were randomized trials or systematic reviews of randomized trials of cannabinoids versus either placebo or active comparator explicitly in adult patients with cancer. RESULTS: Thirty-four systematic reviews and randomized trials met the eligibility criteria for cancer pain. Seven were randomized trials involving patients with cancer pain. Two trials had positive primary endpoints, which could not be reproduced in similarly designed trials. High-quality systematic reviews with meta-analyses found little evidence that cannabinoids are an effective adjuvant or analgesic to cancer pain. Seven systematic reviews and randomized trials related to harms and adverse events were included. There was inconsistent evidence about the types and levels of harm patients may experience when using cannabinoids. CONCLUSION: The MASCC panel recommends against the use of cannabinoids as an adjuvant analgesic for cancer pain and suggests that the potential risk of harm and adverse events be carefully considered for all cancer patients, particularly with treatment with a checkpoint inhibitor.

Validation of the Surprise Question and the Development of a Multivariable Model.

CONTEXT: The Surprise Question (SQ) (would you be surprised if this patient died within a year?) is a prognostic variable explored in chronic illnesses. Validation is limited to sensitivity, specificity, and predictive values. OBJECTIVES: Our objective is to validate the SQ in cancer patients and develop a predictive model with additional variables. METHODS: A prospective cohort study of adult (age>18) cancer patients seen between October 1, 2019, through March 31, 2021, undergoing systemic therapies had the SQ completed by oncologists prior to each change in systemic therapy. The primary outcome was survival for one year. Secondary outcomes were predictions of survival at three, six, and nine months. Patients were grouped into negative SQ (not surprised) and positive SQ (surprised). Sensitivity, specificity, predictive values, and likelihood ratios (LR) were calculated for the SQ. Additional prognostic variables were age, gender, cancer stage, line of therapy, Charleson Comorbid Index (CCI), palliative care consultation (prior to, after the SQ, or not at all), and healthcare utilization (outpatient, inpatient, and emergency department (ED). Logistic regression and receiver operating characteristics (ROC) were used for discrimination and modeling. Akaike information criterion (AIC) was used to compare the model fit as each predictor. RESULTS: 1366 patients had 1 SQ; 784 died within a year. The SQ predicted survival at one year (P = 0.008), with a positive LR of 1.459 (95%CI 1.316-1.602) and a c-statistic of 0.565 (95%CI 0.530-0.600). Additional variables increased the c-statistic to 0.648 (95% CI 0.608-0.686). The total model best predicted survival at three months, c-statistic of 0.663 (95% CI 0.616-0.706). However, the total model c-statistic remained <0.70. CONCLUSIONS: The SQ, as a single factor, poorly predicts survival and should not be used to alter therapies. Adding additional objective variables improved prognostication, but further refinement and external validation are needed.

Multinational Association of Supportive Care in Cancer (MASCC) guidelines: cannabis for psychological symptoms including insomnia, anxiety, and depression.

PURPOSE: During the treatment of cancer, 18% of patients use cannabis for symptom management. Anxiety, depression, and sleep disturbances are common symptoms in cancer. A systematic review of the evidence for cannabis use for psychological symptoms in cancer patients was undertaken to develop a guideline. METHODS: A literature search of randomized trials and systematic reviews was undertaken up to November 12, 2021. Studies were independently assessed for evidence by two authors and then evaluated by all authors for approval. The literature search involved MEDLINE, CCTR, EMBASE, and PsychINFO databases. Inclusion criteria included randomized control trials and systematic reviews on cannabis versus placebo or active comparator in patients with cancer and psychological symptom management (anxiety, depression, and insomnia). RESULTS: The search yielded 829 articles; 145 from Medline, 419 from Embase, 62 from PsychINFO, and 203 from CCTR. Two systematic reviews and 15 randomized trials (4 on sleep, 5 on mood, 6 on both) met eligibility criteria. However, no studies specifically assessed the efficacy of cannabis on psychological symptoms as primary outcomes in cancer patients. The studies varied widely in terms of interventions, control, duration, and outcome measures. Six of 15 RCTs suggested benefits (five for sleep, one for mood). CONCLUSION: There is no high-quality evidence to recommend the use of cannabis as an intervention for psychological symptoms in patients with cancer until more high-quality research demonstrates benefit.

Likelihood Ratios: An Important Concept for Palliative Physicians to Understand.

Palliative care has several tools and questionnaires which are commonly used for patient-related outcomes and prognosis. As an example, the Surprise Question (I would or would not be surprised that this person would have died in a year) has been used as a screen for palliative care referral but also used as a prognostic tool. Diagnostic tests, prognostic tools, and tools for gauging outcomes have certain sensitivity and specificity in predicting a diagnosis or outcome. Clinicians often use positive and negative predictive values in judging the merits of a diagnostic tool or questionnaire. However positive and negative predictive values are highly dependent on the prevalence of disease or outcome in a population and thus are not portable across studies. Likelihood ratios are both portable across populations but also provide the strength of the diagnostic or predictive measure of a test or questionnaire. In this article, we review the value and limitations of likelihood ratios and illustrate the value of using likelihood ratios using 3 studies centered on the Surprise Question published in 2022.

The Financial Impact of Palliative Care and Aggressive Cancer Care on End-of-Life Health Care Costs.

BACKGROUND: Medicare cancer expenditures in the last month of life have increased. Aggressive cancer care at the end-of-life (ACEOL) is considered poor quality care. We used Geisinger Health Plan (GHP) last month's costs for cancer patients who died in 2018 and 2019 to determine the costs of and influence of Palliative Care (PC) on ACEOL. METHOD: Patients with GHP ages 18-99 who died in 2018 and 2019 were included. Demographic, clinical characteristics, and Charlson Comorbid Index were compared across care groups defined as no ACEOL indicator, 1 or more than 1 indicator. Differences between groups were compared with Kruskal-Wallis tests and one-way ANOVA for 3 groups. Median two-sample tests and independent t-tests compared groups of 2. A P-value 1. There were incremental cost increases with each additional ACEOL indicator (p = < .0001). Palliative Care <90 days before death was associated with increased costs while consultations >90 days before death lowered cost (P < .0001) due to reduced chemotherapy in the last month. Completed ADs reduced cost by $4000. DISCUSSION: ACEOL indicators multiply costs during the last month of life. Palliative care instituted >90 days before death reduces chemotherapy in the last month of life and AD reduces health care costs. CONCLUSION: Cancer health care costs increase with indicators of ACEOL. Palliative care consultations >90 days before death; ADs reduce cancer health care costs.

Do We Have Structure, Process and Outcomes to Support Cannabis as Supportive Therapy in Cancer?

Cannabis is becoming more popular and more available in the United States. It has been approved for use by multiple states for various conditions and several states now allow recreational cannabis. We explore the structure of cannabis distribution, the process of acquisition, outcomes, and the safety of cannabis in the United States.

Telemedicine family meetings in palliative care: etiquette.

The use of telemedicine in healthcare settings has continued to increase over the last few years. This has led to new communication-based concerns in palliative care settings. To date, there are no specific guidelines on telemedicine etiqettes relating to conducting online family meetings. This case report discusses some etiquette-failures in a telemedicine family meeting, and offers suggestions to improve communication etiqettes or 'webside manners' in these settings.

Characteristics of Patients with Cancer Readmitted Within 30 Days to an Acute Palliative Care Unit.

OBJECTIVE(S): For patients with cancer, the emergence of acute palliative care units (APCU) may hold promise in curtailing hospital readmissions. The study aims to describe the characteristics of patients readmitted to an APCU. METHODS: This retrospective study examined patients with cancer readmitted within 30 days to an APCU. Readmissions were further classified as either potentially preventable or non-preventable. RESULTS: Out of 734 discharges from July 1, 2014 to July 1, 2015, 69 (9%) readmissions were identified and analyzed. For index admissions, median length of stay was five days, and one (1%) was discharged home with hospice care. For readmissions, median time from index admission to readmission was nine days, median length of stay was six days, three (4%) patients died, and 20 (30%) went home with hospice. Ten (14.5%) readmissions were deemed potentially preventable (95% CI 7.2-25.0%). Race/ethnicity-White/Black/Hispanic/Others-was 60%, 10%, 20% and 10%, respectively, among potentially preventable readmissions and 76%, 22%, 2% and 0%, respectively, among potentially non-preventable readmissions (P = .012). Potentially preventable readmissions were more likely to have venous thromboembolism (40% vs. 12%, P = .046) and more reasons for readmission (median 2 vs. 1, P = .019). CONCLUSIONS: Among patients with cancer readmitted to an APCU, one out of seven was potentially preventable and a far larger proportion was discharged with hospice care compared to the index admission. Recognition of disease course, meaningful goals of care discussions and timely transition to hospice care may reduce rehospitalization in this population.

Is Weight Loss During Chemotherapy for Pancreatic Cancer Prognostic?

BACKGROUND: Predicting poor survival outcomes early in palliative chemotherapy is important to the timing of palliative care. Weight loss during chemotherapy if prognostic would lead to early palliative care. METHOD: We collected demographics, stage, chemotherapy, chemotherapy cycles, weight, healthcare utilization, comorbidities (Charleson Comorbid Index), tumor markers, and weight changes over 60 days. We defined 3 groups of patients: 1. Weight gain to <.5% weight loss, 2. Weight loss< 2% and 3. Weight loss of >2%. A Chi-square test assessed differences in weight during treatment. Time-to-event analysis was expressed in a Kaplan Meier curve. RESULTS: 93 individuals died of pancreatic cancer in 2018 and 2019. The median age was 71.2 years. Forty-three had stage I and II, 40 stages III and IV cancers, and 10 had unknown stages. Most received FOLFIRINOX and gemcitabine/nab-paclitaxel chemotherapy. Thirty-six gained to lost < .5% during chemotherapy,8 lost < 2% and 49 patients lost > 2% of their weight. Mortality was available in 55 of 93 patients. Median survival was 16.6 months in those with weight gain to < .5% weight loss, 17.28 months for those with < 2% weight loss, and 20.5 months for those with > 2% weight loss (P = .42). DISCUSSION: Weight loss over 60 days did not predict a poor prognosis in this small retrospective study; larger prospective studies may clarify the prognostic importance of weight loss during chemotherapy. CONCLUSION: In this small retrospective study, weight loss over 60 days did not predict poor survival.

Top Ten Tips Palliative Care Clinicians Should Know About Buprenorphine.

Pain management in palliative care (PC) is becoming more complex as patients survive longer with life-limiting illnesses and population-wide trends involving opioid misuse become more common in serious illness. Buprenorphine, a generally safe partial mu-opioid receptor agonist, has been shown to be effective for both pain management and opioid use disorder. It is critical that PC clinicians become comfortable with indications for its use, strategies for initiation while understanding risks and benefits. This article, written by a team of PC and addiction-trained specialists, including physicians, nurse practitioners, social workers, and a pharmacist, offers 10 tips to demystify buprenorphine use in serious illness.

Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/consensus guidance on the use of cannabinoids for gastrointestinal symptoms in patients with cancer.

BACKGROUND: Gastrointestinal symptoms are common in patients with cancer, whether related to treatment or a direct effect of the disease itself. Patients may choose to access cannabinoids outside of their formal medical prescriptions to palliate such symptoms. However, clinical guidelines are lacking in relation to the use of such medicines for gastrointestinal symptoms in patients with cancer. METHODS: A systematic review of the evidence for the use of cannabinoids for symptom control in patients with cancer was undertaken. Search strategies were developed for Medline, Embase, PsychINFO, and the Cochrane Central Register of Controlled Trials, including all publications from 1975 up to 12 November 2021. Studies were included if they were randomized controlled trials of cannabinoids compared with placebo or active comparator in adult patients with cancer, regardless of type, stage, or treatment status. Articles for inclusion were agreed by all authors, and data extracted and summarized by two authors. Each study was scored according to the Jadad scale. This review was specifically for the purpose of developing guidelines for the use of cannabis for gastrointestinal symptoms, including chemotherapy-induced nausea and vomiting (CINV), chronic nausea, anorexia-cachexia syndrome, and taste disturbance. RESULTS: Thirty-six randomized controlled trials were identified that met the inclusion criteria for this review of gastrointestinal symptoms: 31 relating to CINV, one to radiotherapy-induced nausea and vomiting, and the remaining four to anorexia-cachexia and altered chemosensory disturbance. The populations for the randomized controlled trials were heterogeneous, and many studies were of poor quality, lacking clarity regarding method of randomization, blinding, and allocation concealment. For CINV, eleven RCTs showed improvement with cannabis compared to placebo, but out of 21 trials where cannabis was compared to other antiemetics for CINV, only 11 favoured cannabis. CONCLUSION: Tetrahydrocannabinol (THC) and nabilone were more effective in preventing CINV when compared to placebo but are not more effective than other antiemetics. For refractory CINV, one study of THC:CBD demonstrated reduced nausea as an add-on treatment to guideline-consistent antiemetic therapy without olanzapine. The MASCC Guideline Committee found insufficient evidence to recommend cannabinoids for the management of CINV, nausea from advanced cancer, cancer-associated anorexia-cachexia, and taste disturbance. High-quality studies are needed to inform practice.

Pregabalin for chemotherapy-induced neuropathy: background and rationale for further study.

Chemotherapy-induced neuropathy is difficult to manage, and the pain associated with neuropathy is poorly responsive to gabapentin in a randomized trial. Duloxetine is the only drug that has been found to be effective in reducing pain from chemotherapy neuropathy. In this qualitative review, the use of pregabalin for chemotherapy-induced neuropathy is discussed including the rationale and pharmacological reasons why pregabalin should be considered in a large, randomized placebo-controlled trial.