Should We Use COMM (Current Opioid Misuse Measure) to Screen for Opioid Abuse in Patients With Cancer Pain?

BACKGROUND: Growing concerns about opioid use disorder (OUD) and the resulting decrease in opioid availability for patients with cancer pain highlight the need for reliable screening tools to identify the subset of patients at increased risk for aberrant opioid use. Our study examines the utility of Current Opioid Misuse Measure (COMM) recommended by the NCCN Clinical Practice Guidelines in Oncology for Adult Cancer Pain. PATIENTS AND METHODS: We analyzed prospectively collected patient-reported outcomes of 444 consecutive patients with cancer seen in pain clinics of a cancer center at 2 time points within 100 days. The relationship of COMM to other OUD screening tools, pain, opioid doses, patient demographics, and mortality was examined using univariate and multivariable logistic regression. We also examined individual items of COMM for face validity. RESULTS: Among 444 patients who completed pain surveys at 2 time points, 157 (35.4%) did not complete COMM surveys. Using a COMM cutoff of ≥13, a total of 84 patients (29.3%; 84/287) scored positive for aberrant drug use. As patients remained on opioids for 49 to 100 days, the likelihood of improving COMM score (turning from positive to negative) was 6.1 times greater than the reverse. The number of patients with COMM ≥13 was 3.8 times higher than the number of patients with CPT diagnostic codes for OUD, 5.3 times higher than those with a positive urine drug screening, and 21 times higher than those with a positive CAGE (Cut Down, Annoyed, Guilty, Eye-Opener Questionnaire) score. COMM ≥13 was not associated with pain relief response (worst pain intensity score ≥2 points on the Brief Pain Inventory), opioid doses, gender, or age. Contrary to the intended use of COMM to identify aberrant opioid use, COMM ≥13 predicted mortality: patients with COMM ≥13 were 1.9 times more likely to die within 12 months. CONCLUSIONS: Our study found that using COMM in a cancer population may significantly overestimate the risk of opioid misuse. Using COMM without modifications can create an additional barrier to cancer pain management, such as limiting appropriate opioid use.

NCCN Guidelines® Insights: Survivorship, Version 1.2023.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals address the complex and varied needs of cancer survivors. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for psychosocial and physical problems resulting from adult-onset cancer and its treatment; recommendations to help promote healthy behaviors and immunizations in survivors; and a framework for care coordination. These NCCN Guidelines Insights summarize recent guideline updates and panel discussions pertaining to sleep disorders, fatigue, and cognitive function in cancer survivors.

NCCN Guidelines® Insights: Survivorship, Version 1.2022.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals who work with survivors to ensure that the survivors' complex and varied needs are addressed. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for the consequences of adult-onset cancer and its treatment; recommendations to help promote physical activity, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes updates to the NCCN Guidelines pertaining to preventive health for cancer survivors, including recommendations about alcohol consumption and vaccinations.

Pharmacologic Management of Persistent Pain in Cancer Survivors.

Improvements in screening, diagnosis and treatment of cancer has seen cancer mortality substantially diminish in the past three decades. It is estimated there are almost 20 million cancer survivors in the USA alone, but some 40% live with chronic pain after completing treatment. While a broad definition of survivorship that includes all people living with, through and beyond a cancer diagnosis-including those with active cancer-is often used, this narrative review primarily focuses on the management of pain in people who are disease-free after completing primary cancer treatment as adults. Chronic pain in this population needs a different approach to that used for people with a limited prognosis. After describing the common chronic pain syndromes caused by cancer treatment, and the pathophysiologic mechanisms involved, the pharmacologic management of entities such as post-surgical pain, chemotherapy-induced neuropathy, aromatase inhibitor musculoskeletal syndrome and checkpoint inhibitor-related pain are described. The challenges  associated with opioid prescribing in this population are given special attention. Expert guidelines on pain management in cancer survivors now recommend a combination of pharmacologic and non-pharmacologic modalities, and these are also briefly covered.

Safety of opioid prescribing among older cancer survivors.

BACKGROUND: Cancer survivors receive more long-term opioid therapy (LTOT) than people without cancer, but the safety of LTOT prescribing is unknown. METHODS: Opioid-naive adults aged ≥66 years who had been diagnosed in 2008-2015 with breast, lung, head and neck, or colorectal cancer were identified with data from Surveillance, Epidemiology, and End Results cancer registries linked with Medicare claims. Survivors with 1 or more LTOT episodes (≥90 consecutive days) occurring ≥1 year after their cancer diagnosis and before censoring at hospice entry, another cancer diagnosis, 6 months before death, or December 2016 were included. The safety of prescribing during the first 90 days of the first LTOT episode was measured during follow-up. As a positive safety indicator, the proportion of survivors with concurrent nonopioid pain management was measured. Indicators of less safe prescribing were the proportion of survivors with a high average daily opioid dose (≥90 morphine milligram equivalents) and the proportion of survivors with concurrent benzodiazepine dispensing. Multivariable logistic regression analyses were conducted to identify clinical predictors of each safety outcome. RESULTS: In all, 3628 cancer survivors received LTOT during follow-up (median duration, 4.9 months; interquartile range, 3.5-8.0 months). Seventy-two percent of the survivors received multimodal pain management concurrently with LTOT. Eight percent of the survivors had high-dose opioid prescriptions; 25% of the survivors received benzodiazepines during LTOT. Multivariable analyses identified variations in safety measures by multiple clinical factors, although none were consistently significant across outcomes. CONCLUSIONS: To improve safe LTOT prescribing for survivors, efforts should focus on increasing multimodal pain management and reducing inappropriate benzodiazepine prescribing. Different clinical predictors of each outcome suggest different drivers of safe prescribing.

Fostering Trust With a Young Man Experiencing Homelessness and Advanced Cancer.

Persons experiencing homelessness (PEH) face countless barriers to equitable health, social, and palliative care across all settings. Brandon was a 23-year-old male, well-spoken, groomed, and polite despite difficult circumstances. He was severely abused then abandoned as a child, living in multiple foster homes until 18. With no consistent caring adult figure, he predictably fell into a chaotic lifestyle, had 3 children by different mothers, and became homeless in New York City. He presented with newly diagnosed renal cell carcinoma metastatic to lung, lymph nodes, and bone. Spine and pelvic metastases caused paralyzing somatic pain that interfered with walking and sitting and prevented Brandon from performing the activities of daily living essential for his survival on the streets and safekeeping of opioids. Lack of basic social support and a history of multiple abandonments made a care plan for this young, homeless, and truly isolated man very challenging. The inpatient and outpatient interdisciplinary team members partnering with Brandon each earned his trust with time. A "safe place" opened hearts on all sides of the therapeutic relationship and led to a plan that was acceptable for both the patient and the palliative care team. Clinicians are often challenged to provide sustained and pragmatic palliative care services for PEH due to complex barriers. Continued advocacy for equitable and tailored services that ensure high-quality palliative care for PEH is critical at individual, institutional, and system levels to promote health equity and dignified care.

Survivorship, Version 1.2021.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals working with cancer survivors to ensure that each survivor's complex and varied needs are addressed. The Guidelines provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment; recommendations to help promote healthful lifestyle behaviors, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes the recommendations regarding employment and return to work for cancer survivors that were added in the 2021 version of the NCCN Guidelines.

A Phase II, Nonrandomized Open Trial Assessing Pain Efficacy with Radium-223 in Symptomatic Metastatic Castration-resistant Prostate Cancer.

BACKGROUND: Prostate Cancer Working Group 3 and FDA guidelines recommend a standardized approach to pain assessment in preapproval trials. No prior trial has examined pain palliation of Radium-223 using standard dosing and contemporary PRO pain-assessment tools. METHODS: In this multicenter phase II trial, patients with Brief Pain Inventory (BPI) ≥3 were eligible for Radium-223 per its label. Primary endpoint was a 30% decrease in BPI Worst Pain from baseline to Week 8, sustained at Week 12 without escalation of medication on the World Health Organization (WHO) analgesic ladder. Secondary endpoints included changes in Brief Fatigue Inventory (BFI) Worst fatigue and BPI pain interference. If six of 27 subjects (22%) met the primary endpoint, the trial would expand by another 36 subjects. RESULTS: Twenty-nine subjects were accrued. Nine of 29 (31%) subjects met the primary endpoint, with 21 (72%) evaluable for the primary endpoint. Among responders: median worst pain declined 62% (range 36-100) at Week 8 and 63% (range 38-100) at Week 12; median reduction of pain interference with general activity and sleep at Week 12 was 62% (range 18-100) and 53% (range 8-100) respectively; median reduction in worst fatigue of 45% (range 10-85) at Week 12. CONCLUSIONS: In the first prospective trial using standard Ra-223 doses, contemporary pain endpoints and PRO collection tools, Ra-223 palliated pain, reduced fatigue, and improved pain interference. The pain response rate easily exceeded the requirements for expansion to the second phase, but the trial was closed due to slow accrual.

Trends in chronic opioid therapy among survivors of head and neck cancer.

BACKGROUND: Survivors of head and neck cancer (HNC) have increased risk of opioid misuse. METHODS: Using Surveillance, Epidemiology and End-Results-Medicare data, we matched adults ≥66 years diagnosed with HNC 2008-2015 with cancer-free controls. We computed odds ratios (OR) for receipt of chronic opioid therapy (COT, claims for ≥90 consecutive days) for HNC survivors compared to controls each year after matching through 2016. RESULTS: The cohort of HNC survivors declined from 5107 in the first year after diagnosis to 604 in the sixth year after diagnosis. For 5 years, rates of COT among HNC survivors exceeded that of controls. Differences between survivors and controls declined each year (ORs: year 1, 4.36; year 2, 2.60; year 3, 2.18; year 4, 1.85; and year 5, 1.35; all P-values <.05). CONCLUSIONS: Among older HNC survivors, cancer-associated opioid use in the first years after diagnosis suggests that the benefit of opioids must balance the risk of opioid misuse.

NCCN Guidelines Insights: Survivorship, Version 2.2020.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment, with the goal of helping healthcare professionals who work with survivors, including those in primary care. The guidelines also provide recommendations to help clinicians promote physical activity, weight management, and proper immunizations in survivors and facilitate care coordination to ensure that all of the survivors' needs are addressed. These NCCN Guidelines Insights summarize additions and changes made to the guidelines in 2020 regarding cardiovascular disease risk assessment and screening for subsequent primary malignancies.

Successful use of buprenorphine-naloxone medication-assisted program to treat concurrent pain and opioid addiction after cancer therapy.

Cancer pain is often treated with opioids, a therapeutic regimen that can become a challenge in patients with an opioid use disorder (OUD). While use of the buprenorphine-naloxone combination is an effective medication-assisted treatment (MAT) for OUD, its use in pain patients with OUD has been controversial due to concerns that co-administration of buprenorphine can reduce or block analge-sia and precipitate opioid withdrawal in those patients requiring full opioid agonists. Data on its use in cancer pain patients are lack-ing. In this case series, the authors explore the frequency of buprenorphine-naloxone use and its outcomes in patients in a Compre-hensive Care Center (CCC) Pain Registry. OUD was deduced from an International Classification of Diseases (ICD-10) diagnostic code for opioid-related disorders recorded in the electronic medical records. Of 2,320 chronic cancer pain patients, 125 patients had ICD-10 code for opioid-related disorders, and 43 had a diagnosis of opioid abuse of whom 11 received buprenorphine-naloxone combina-tions. Eight patients on 18 (6-24) mg per day of buprenorphine-naloxone remained in therapy for 4 (2-7) years without opioid abuse relapse. This assessment was based on clinician's notes, the Prescription Monitoring Program, random urine drug screening, and the absence of Urgent Care Center visits for opioid withdrawal or overdose. When short-term opioids were administered for acute pain, these patients were able to taper down and stop them quickly without an opioid abuse relapse. Buprenorphine-naloxone was effec-tive as the sole analgesic in selected patients. Given its success at the CCC, buprenorphine-naloxone should be made available and strongly considered as a treatment for patients suffering from OUD during and following cancer treatment and when cancer pain re-duces or resolves.

Does transdermal fentanyl work in patients with low BMI? Patient-reported outcomes of pain and percent pain relief in cancer patients on transdermal fentanyl.

BACKGROUND: Low body mass index (BMI) is suspected of being associated with low transdermal fentanyl (TDF) blood levels and worse pain relief. Clinical pain data to support this claim are lacking. METHODS: Using a Chronic Pain Registry, we identified 901 cancer patients who received TDF at outpatient pain service clinics of our cancer center from 7/1/2011 to 12/1/2016. Of these, 240 patients had a BMI measure, pain intensity, and pain relief scores documented within 30 days of a TDF order. We examined associations between BMI, TDF dose, Worst and Least pain scores, and pain relief scores using standard statistical tests. RESULTS: In cancer patients receiving TDF, low BMI (<18.5) was significantly associated with greater pain relief irrespective of TDF dose and borderline significantly associated with greater percent pain relief after controlling for age, cancer diagnoses, and pain etiology (P = .073), suggesting that low BMI may independently predict better pain relief in cancer patients. As there were no significant associations between BMI and TDF dose, we find no basis for BMI-dependent dose modification or avoiding TDF in cachectic and low BMI patients. CONCLUSIONS: When predicting percent pain relief, we conclude that there is no basis for avoiding TDF or modifying its dose in cancer patients with low BMI and cachexia.

Adult Cancer Pain, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

In recent years, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain have undergone substantial revisions focusing on the appropriate and safe prescription of opioid analgesics, optimization of nonopioid analgesics and adjuvant medications, and integration of nonpharmacologic methods of cancer pain management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic interventions, nonpharmacologic interventions, and treatment of specific cancer pain syndromes. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.

Trends in Opioid Use Among Older Survivors of Colorectal, Lung, and Breast Cancers.

PURPOSE: Cancer survivors may be at increased risk for opioid-related harms. Trends in opioid use over time since diagnosis are unknown. METHODS: Using data from SEER and Medicare, we conducted multilevel logistic regression analyses to compare chronic opioid use (≥ 90 consecutive days) among opioid-naïve survivors of colorectal, lung, and breast cancers diagnosed from 2008 to 2013 and matched with noncancer controls. Among cases and controls with chronic use, we compared rates of high-dose opioid use (average ≥ 90 morphine milligram equivalents daily). RESULTS: We included 46,789 survivors and 138,136 noncancer controls. In the first year after the index date (survivor's diagnosis date), chronic use among colorectal and lung cancer survivors exceeded chronic use among controls (colorectal cancer: odds ratio, 1.34; 95% CI, 1.22 to 1.47; lung cancer: odds ratio, 2.55; 95% CI, 2.34 to 2.77). Differences in chronic use between survivors and controls declined each year after the index date. Chronic use among breast cancer survivors was less than that of controls each year after the index date. Survivors with chronic use were more likely to have a high daily dose than controls with chronic use in the first 3 to 5 years. CONCLUSION: Among three large populations of older cancer survivors, chronic opioid use varied by cancer. However, by 6 years after diagnosis, survivors were no longer more likely to be chronic users than controls. Strategies for appropriate pain management during and after cancer treatment should take into account the risks associated with chronic high-dose opioid use.

Patient-Reported Outcomes and Opioid Use by Outpatient Cancer Patients.

The Memorial Sloan Kettering Pain Registry contains patient characteristics, treatments, and outcomes for a prospective cohort of 1,534 chronic pain cancer patients who were seen at outpatient pain service clinics. Average pain intensity (Brief Pain Inventory) was reported as mild by 24.6% of patients, moderate by 41.5%, and severe by 33.9%. The patient's report of average percent pain relief and health state (EuroQOL 5 dimensions) was inversely related to average pain intensity category, whereas measures of pain interference, number of worst pain locations, and physical and psychological distress were directly related to pain intensity category. Eighty-six percent of patients received an opioid at 1 or more clinic encounters. Regression analysis revealed that male sex or being younger (65 years of age or younger) was associated with a greater likelihood of an opioid ordered. Male sex nearly doubled the likelihood of a higher dose being ordered than female sex. Bivariate analysis found that patients receiving opioids reported significantly more pain relief than no-opioid patients. However, patients receiving opioids had higher pain interference scores, lower index of health state, and more physical distress than no-opioid patients Our results identify the need to consider opioid use and dosage when attempting to understand patient-reported outcomes (PROs) and factors affecting pain management. PERSPECTIVE: This report describes the results of the analyses of PROs and patient-related electronic health record data collected under standard of care from cancer patients at outpatient pain management clinics of Anesthesiology and Palliative Care at the Memorial Sloan Kettering Cancer Center. Consideration of sex and age as predictors of opioid use is critical in attempting to understand PROs and their relationship to pain management.

A phase I study of D-methadone in patients with chronic pain.

D-Methadone is the d optical isomer of racemic mixture (DL-methadone) used clinically to treat pain and addiction in the United States. D-Methadone is practically devoid of opioid activity but maintains N-methyl-D-aspartate (NMDA) receptor antagonism. Evidence from extensive preclinical studies suggests that NMDA receptor antagonists attenuate neuronal plasticity, reverse opioid analgesic tolerance, and alleviate chronic pain states. The authors conducted a phase I open label study of D-methadone administered for the first time to patients with chronic pain to determine the safety and tolerability of D-methadone. In addition to their long-term regimen of opioids, the patients received 40 mg of D-methadone twice daily for 12 days. Analgesia and toxicity were recorded by the patients in a daily diary and assessed in clinic on days 1, 8, and 12. Eight patients of the 10 enrolled completed the study. Pain scores on Edmonton Symptom Assessment System (ESAS) did not change between days 1 and 12, but five of eight patients (62.5 percent) characterized D-methadone as moderately or very effective in relieving pain on the Global Assessment for pain. Five of the eight patients (62.5 percent) who completed the study requested to start treatment with commercially available methadone (DL-racemic methadone) after completing the study. D-Methadone at the dose of 40 mg PO Q 12 hours was well tolerated. Perspective: This is the first clinical study of D-methadone in patients suffering from chronic pain. Additional phase I and phase II studies are needed to confirm its safety and analgesic effects. If D-methadone is well tolerated, it is likely to become a useful adjuvant to the treatment of a wide spectrum of pain syndromes.

Methadone Use and the Risk of Hypoglycemia for Inpatients With Cancer Pain.

CONTEXT: Methadone is an important drug in the management of both cancer-related and non-cancer-related pain and is the main pharmacologic agent used in the treatment of opioid addiction. Unexpected hypoglycemia has been observed in patients receiving methadone, prompting a more detailed investigation. OBJECTIVES: To evaluate the incidence of hypoglycemia in a cohort of inpatients receiving methadone versus other opioids including fentanyl, hydromorphone, and morphine. METHODS: Retrospective observational cohort of inpatients in a tertiary cancer center admitted for more than 48 hours from November 1, 2011 to October 30, 2013. The main outcomes were lowest measured daily blood glucose (in mg/dL) and incidence of hypoglycemia (defined as blood glucose < 70 mg/dL, equivalent to 3.9 mmol/L) with variable methadone doses compared with other non-methadone opioids. RESULTS: Of the 641 eligible patients admitted during the study period who received at least one dose of methadone during admission, multivariable logistic regression showed significant associations between methadone and hypoglycemia at doses greater than 40 mg oral equivalents per day or with patient-controlled analgesia use. A dose-response relationship was observed, with an odds ratio of 3.1 (95% confidence interval 2.5, 3.6) when doses greater than 80 mg/day were used. No evidence of increased risk of hypoglycemia or of a dose-response curve was seen for the other opioids. CONCLUSION: The risk of hypoglycemia is increased for patients taking more than 40 mg oral methadone equivalents per day. When starting methadone at or more than 40 mg/day, we recommend blood glucose monitoring.

Pain in cancer survivors.

Pain is a common problem in cancer survivors, especially in the first few years after treatment. In the longer term, approximately 5% to 10% of survivors have chronic severe pain that interferes with functioning. The prevalence is much higher in certain subpopulations, such as breast cancer survivors. All cancer treatment modalities have the potential to cause pain. Currently, the approach to managing pain in cancer survivors is similar to that for chronic cancer-related pain, pharmacotherapy being the principal treatment modality. Although it may be appropriate to continue strong opioids in survivors with moderate to severe pain, most pain problems in cancer survivors will not require them. Moreover, because more than 40% of cancer survivors now live longer than 10 years, there is growing concern about the long-term adverse effects of opioids and the risks of misuse, abuse, and overdose in the nonpatient population. As with chronic nonmalignant pain, multimodal interventions that incorporate nonpharmacologic therapies should be part of the treatment strategy for pain in cancer survivors, prescribed with the aim of restoring functionality, not just providing comfort. For patients with complex pain issues, multidisciplinary programs should be used, if available. New or worsening pain in a cancer survivor must be evaluated to determine whether the cause is recurrent disease or a second malignancy. This article focuses on patients with a history of cancer who are beyond the acute diagnosis and treatment phase and on common treatment-related pain etiologies. The benefits and harms of the various pharmacologic and nonpharmacologic options for pain management in this setting are reviewed.

Adult cancer pain.

Pain is a common symptom associated with cancer and its treatment. Pain management is an important aspect of oncologic care, and unrelieved pain significantly comprises overall quality of life. These NCCN Guidelines list the principles of management and acknowledge the range of complex decisions faced in the management oncologic pain. In addition to pain assessment techniques, these guidelines provide principles of use, dosing, management of adverse effects, and safe handling procedures of pharmacologic therapies and discuss a multidisciplinary approach for the management of cancer pain.