Dylan Zylla

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

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.

Association of opioid requirement and cancer pain with survival in advanced non-small cell lung cancer

BACKGROUND Pain is associated with shorter survival in non-small cell lung cancer (NSCLC). Lung cancer cells express opioid receptors. Opioids promote angiogenesis, tumour growth, and metastases, and shorten survival in animal models. METHODS We examined retrospectively if long-term opioid requirement, independently of chronic pain, is associated with reduced survival in 209 patients with stage IIIB/IV NSCLC. Opioid doses were converted to average oral morphine equivalents (OME). Patients were stratified by proportion of time they reported severe pain, and required <5 or ≥5 mg day-1 OME. Effects of pain, opioid requirement, and known prognostic variables on overall survival were analysed. RESULTS Severe pain before chemotherapy initiation was associated with shorter survival (hazards ratio 1.39, 95% confidence interval, 1.02-1.87, P=0.035). The magnitude of pain and opioid requirement during first 90 days of chemotherapy were predictive of shorter survival: patients with no/mild pain and requiring <5 mg day-1 OME had 12 months longer median survival compared with those requiring more opioids, experiencing more pain, or both (18 compared with 4.2-7.7 months, P≤0.002). Survival differences (16 compared with 5.5-7.8 months, P<0.001) were similar when chronic pain and opioid requirement were assessed until death or last follow-up. In multivariable models, opioid requirement and chronic pain remained independent predictors of survival, after adjustment for age, stage, and performance status. CONCLUSIONS The severity of chronic cancer-related pain or greater opioid requirement is associated with shorter survival in advanced NSCLC, independently of known prognostic factors. While pain adversely influences prognosis, controlling it with opioids does not improve survival. Prospective studies should determine if pain control using equi-analgesic opioid-sparing approaches can improve outcomes.

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 hosts 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.

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

PurposePain 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.MethodsA 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.ResultsFifty 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.ConclusionsPain 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.

Establishment of Personalized Pain Goals in Oncology Patients to Improve Care and Decrease Costs

PURPOSE Cancer-related pain is common, negatively affects quality of life and survival, and often requires treatment with opioid analgesics. Patient-reported data that describe the incidence and severity of pain, medication use, and patient satisfaction with care are lacking. METHODS We analyzed 18 months of outpatient oncology clinic encounters from the electronic medical record to obtain data on pain levels and opioid and nonopioid treatments. In June 2014, we instituted a pain intervention by creating a pain management information handout for patients, educating clinicians on opioid cost-effectiveness, and implementing a nursing protocol to document personalized pain goals (PPGs). RESULTS Moderate to severe pain was reported in nearly 15% of patient encounters. We observed an increase in the percentage of encounters with a documented PPG of 16% to 71% ( P < .001). On average, PPG was achieved in 84% of patients. Rates of high-cost long-acting opioid prescriptions (oxycodone controlled release and fentanyl patches), as a total of all long-acting opioids, declined from 45% preintervention to 33% postintervention ( P = .005). CONCLUSION Our intervention improved rates of PPG documentation and decreased the number of prescriptions for high-cost long-acting opioids. Oncology clinics can implement simple quality improvement methods, such as asking patients about their PPG and educating clinicians about opioid costs, to improve outcomes and lower treatment costs.

Impact of opioid use on survival in patients with newly diagnosed stage IV non-hematologic malignancies.

188 Background: Pain is a challenging problem in patients with advanced cancers. Opioids are commonly required to treat cancer-related pain, but may be associated with tumor progression and shorter survival. We recently reported that high opioid use during the first 90 days after diagnosis is associated with shorter survival in patients with advanced lung cancer. METHODS We identified 1386 newly diagnosed stage IV non-hematologic malignancies from 2005-2013 and gathered pain and opioid utilization within 90 days of treatment using data from electronic medical records and the tumor registry. Opioid utilization was stratified into low opioid exposure (LOE; no opioid prescriptions or one prescription for a short-acting opioid) and high opioid exposure (HOE; any long-acting opioid prescription or 2 or more short-acting opioid prescriptions). Pain was analyzed by the proportion of time patients reported levels of moderate-severe pain (i.e., pain level ≥ 4). The effects of opioid exposure, prognosis of tumor type ( < 1 year vs ≥ 1 year), and gender on overall survival were analyzed in univariable and multivariable models. RESULTS Patients in the HOE (n = 887) and LOE (n = 499) groups were well matched for age, gender, and tumor type. Moderate-severe pain was higher in the HOE group compared to the LOE group (29.3% vs 14.0%). HOE was associated with shorter median survival compared to LOE (7.2 vs 13.2 months, p-value < 0.0001). On multivariable analysis, HOE was associated with shorter overall survival after adjusting for age, gender and tumor prognosis (HR 1.4, 95% CI 1.2- 1.6) (Table). CONCLUSIONS Results support prior studies of advanced prostate and lung cancers, and show early utilization of opioids is a strong prognostic factor for survival. Further prospective investigation on the role of opioid receptors and opioid utilization is urgently needed. [Table: see text].

Pain score, analgesic utilization, and patient satisfaction among cancer patients at a community cancer center.

203 Background: Cancer-related pain is common, negatively impacts quality of life and survival, and often requires opioid analgesics. Patient level data describing the incidence and severity of pain, medication utilization, and patient satisfaction associated with care are lacking. An understanding of cancer pain prevalence and analgesic utilization is needed to initiate quality improvement (QI) interventions. METHODS We analyzed 2 months of outpatient oncology clinic encounters from the electronic medical record (EMR) and conducted a patient survey of 163 cancer patients to obtain baseline data on pain levels, opioid and non-opioid treatments, and patient satisfaction. Our survey incorporated questions from the Brief Pain Inventory to validate EMR reports and obtain patient satisfaction data. RESULTS Moderate to severe pain is reported in nearly 1 of every 9 cancer patient encounters (Table 1). On average, we achieved a personal pain goal (PPG) in 83.5 % of all patients (n=109). Among patients receiving opioids, a PPG was achieved in 16 of 29 patients (55.2%). Of the 13 opioid-consuming patients not achieving a PPG, 12 were not on a long-acting opioid, and 5 had never discussed a pain management plan with their physician. Oxycodone CR is the most commonly prescribed long-acting opioid (40.4% versus morphine SR (26.1%), methadone (23.0%), and fentanyl transdermal (10.6%)). CONCLUSIONS Moderate to severe pain is commonly encountered among patients receiving cancer care in the clinic setting. Increasing the proportion of patients achieving a PPG is a critical quality and patient satisfaction goal, and may be improved by creating a pain plan incorporating a long-acting opioid. Our QI intervention aims to improve pain assessment documented in the EMR and educate both patients and staff regarding appropriate pain management. [Table: see text].

Association of opioid requirement and cancer pain with survival in advanced non-small cell lung cancer.

183 Background: Pain is associated with shorter survival in non-small cell lung cancer (NSCLC). Lung cancer cells express opioid receptors. Opioids promote angiogenesis, tumor growth and metastases, and shorten survival in animal models. METHODS To examine if long-term opioid requirement, independently of chronic pain, is associated with survival, we studied 209 patients treated with chemotherapy for stage IIIB/IV NSCLC. Pain was stratified by proportion of time patients reported specific levels of pain. Opioids were converted to oral morphine equivalents (OME) for comparison. The effects of pain, opioid requirement, and known prognostic variables on survival were analyzed in univariable and multivariable models. RESULTS Both severity of pain and greater opioid requirement in first 90 days after starting chemotherapy were strongly predictive of shorter survival on univariable analysis. Patients with no/mild chronic pain and requiring <5 mg/day OME during first 90 days had nearly 12 months longer median survival compared to patients requiring ≥5 mg/day OME and/or experiencing more pain. Differences in survival remained remarkably similar when chronic pain and opioid requirement were assessed over the entire clinical course (until death or last follow-up). In multivariable models, both opioid requirement and chronic pain remained independent predictors of survival, after adjustment for age, stage and performance status. CONCLUSIONS Severity of chronic cancer-related pain or greater opioid requirement are associated with shorter survival in advanced NSCLC, independently of known prognostic factors. While pain adversely influences prognosis, controlling it with opioids does not improve survival. Prospective studies should determine if achieving pain control using opioid-sparing approaches improves outcomes.