O-Glycome Profiling of Breast Cancer Cell Lines to Understand Breast Cancer Brain Metastasis.

Breast cancer is the second leading cause of cancer-related death among women and a major source of brain metastases. Despite the increasing incidence of brain metastasis from breast cancer, the underlying mechanisms remain poorly understood. Altered glycosylation is known to play a role in various diseases including cancer metastasis. However, profiling studies of O-glycans and their isomers in breast cancer brain metastasis (BCBM) are scarce. This study analyzed the expression of O-glycans and their isomers in human breast cancer cell lines (MDA-MB-231, MDA-MB-361, HTB131, and HTB22), a brain cancer cell line (CRL-1620), and a brain metastatic breast cancer cell line (MDA-MB-231BR) using nanoLC-MS/MS, identifying 27 O-glycan compositions. We observed significant upregulation in the expression of HexNAc1Hex1NeuAc2 and HexNAc2Hex3, whereas the expression of HexNAc1Hex1NeuAc1 was downregulated in MDA-MB-231BR compared to other cell lines. In our isomeric analysis, we observed notable alterations in the isomeric forms of the O-glycan structure HexNAc1Hex1NeuAc1 in a comparison of different cell lines. Our analysis of O-glycans and their isomers in cancer cells demonstrated that changes in their distribution can be related to the metastatic process. We believe that our investigation will contribute to an enhanced comprehension of the significance of O-glycans and their isomers in BCBM.

Coping Strategies and Associated Symptom Burden Among Patients With Advanced Cancer.

BACKGROUND: Few studies examine how patients with advanced cancer cope with stress. The objective of our study was to evaluate coping strategies adopted by patients with cancer and their relationship with symptom burden. METHODS: A secondary data analysis of a prospective cross-sectional survey of patients with cancer and tobacco use was conducted, which examined demographics, symptom burden (Edmonton Symptom Assessment System), and coping strategies (the Brief COPE Questionnaire). Demographic characteristics were summarized by standard summary statistics; we also examined associations between patient characteristics and coping strategies using t-test, rank-sum test, chi-squared test, or Fisher's exact test depending on the distribution of data. RESULTS: Among 399 patients, the majority were female (60%), Caucasian (70%), the mean age was 56.5 (±12.0) years, and the most common malignancies were gastrointestinal (21%) and breast (19%). Patients with cancer adopted multiple adaptive coping strategies, most frequently acceptance (86.7%) and emotional support (79.9%), with humor (18.5%) being the least. Common maladaptive strategies included venting (14.5%) and self-distraction (36.6%), while substance use (1.0%) was infrequently reported. Of the adaptive strategies, female gender was significantly associated with higher engagement with emotional and instrumental support, positive reframing, religious coping, and acceptance (P < .05 for all). College educated patients reported significantly higher implementation of humor, planning, and acceptance. Maladaptive coping strategies such as denial were associated with increased pain and depression, while patients adopting emotional-focused strategies rated decreased emotional distress. CONCLUSIONS: The majority of patients with advanced cancer reported adopting multiple, adaptive coping strategies, and a minority utilized maladaptive or avoidant strategies, rarely substance use, and may need additional psychological support.

Midfacial Toddler Excoriation syndrome (MiTES): case series, diagnostic criteria and evidence for a pathogenic mechanism.

BACKGROUND: PRDM12 polyalanine tract expansions cause two different disorders; Midfacial Toddler Excoriation Syndrome (MiTES) - itch with normal pain sensation associated with homozygous 18 alanines (18A), and congenital insensitivity to pain (CIP) with normal itch with homozygous 19A. Knowledge of the phenotype, genotype, and disease mechanism of MiTES is incomplete. Why PRDM12 18A versus 19A can cause almost opposite phenotypes is unknown; no other poly-alanine or poly-glutamine tract expansion disease causes two such disparate phenotypes. METHODS: We assessed the genotype and phenotype of 9 new, 9 atypical, and 6 previously reported patients diagnosed with MiTES. Using cell lines with homozygous PRDM12 of 12A (normal), 18A (MiTES) and 19A (CIP) we examined PRDM12 aggregation and subcellular localisation by image separation confocal microscopy and sub-cellular fractionation western blotting. RESULTS: MiTES presents in the first year of life, and in all cases the condition regresses over the first decade leaving scarring. The MiTES phenotype is highly distinctive. Features overlapping with PRDM12-CIP are rarely found. The genotype-phenotype study of PRDM12 polyalanine tract shows that 7A -15A are normal; 16A -18A are associated with MiTES; 19A leads to CIP; and no clinically atypical MiTES cases had an expansion. PRDM12 aggregation and sub-cellular localisation differ significantly between 18A and normal 12A cell lines and between 18A and 19A cell lines. MiTES is a new protein aggregation disease. CONCLUSION: We provide diagnostic criteria for MiTES, and improved longitudinal data. MiTES and CIP are distinct phenotypes despite their genotypes varying by a single alanine in the PRDM12 polyalanine tract. We found clear distinctions between the cellular phenotypes of normal, MiTES and CIP cells.. We hypothesise that the developmental environment of the trigeminal ganglion is unique and critically sensitive to prenatal and postnatal levels of PRDM12.

Reliability of urine drug testing among patients on buprenorphine transdermal patch.

BACKGROUND: Urine drug testing (UDT) plays a significant role in monitoring patients on chronic opioid therapy (COT) for non-medical opioid use (NMOU). UDT, at times, can be inconsistent and misleading. We present a case where a patient on a buprenorphine patch had false negative results. CASE DESCRIPTION: A female in her 70s with metastatic breast cancer presented with uncontrolled pain from a T6 compression fracture. She had no relief with tramadol 50 mg every 6 hours as needed. Due to an allergic reaction to hydromorphone, our team prescribed a buprenorphine patch of 5 µg/h. Subsequently, she expressed excellent pain control, and the clinician confirmed the patch placement on examination. She underwent a UDT during the visit. The UDT was negative for both buprenorphine and its metabolites. The literature review showed that false negative UDT results are relatively common among patients with low-dose buprenorphine patches. The combination of a thorough physical examination, a review of the Prescription Drug Monitoring Program, and reassuring scores on screening tools placed her at low risk for NMOU. DISCUSSION: Buprenorphine has a ceiling effect on respiratory depression and a lower risk for addiction. However, when used in low doses, the drug might not have enough metabolites in the urine, leading to a false negative UDT. Such results might affect patient-physician relationships. CONCLUSION: In addition to the UDT, a thorough history, screening for NMOU, physical exam, a review of PDMP, and a good understanding of opioid metabolism are necessary to help guide pain management.

Interdisciplinary intervention for the management of nonmedical opioid use among patients with cancer pain.

BACKGROUND: Few studies have assessed interventions aimed at managing nonmedical opioid use (NMOU) behavior among patients with cancer. The authors developed the Compassionate High-Alert Team (CHAT) intervention to manage patients receiving opioids for cancer pain who demonstrate NMOU behavior. The objective of this study was to determine the change in frequency of NMOU behaviors, pain intensity, and opioid requirements among those who received the intervention. METHODS: A total of 130 patients receiving opioids for cancer pain that had documented evidence of NMOU and received the CHAT intervention were reviewed. Demographic and clinical information such as NMOU behaviors, pain scores, and morphine equivalent daily dose at baseline, 3, and 6 months post-intervention was obtained. RESULTS: NMOU behaviors significantly decreased from a median (interquartile range) of 2 (1-3) at baseline to 0 (0-1) at both 3 and 6 months post-intervention (p < .001). A total of 45 of 75 (60%) and 31 of 50 (62%) of CHAT recipients achieved complete response to the intervention at 3 and 6 months, respectively. Higher baseline number of NMOU behaviors was independently associated with patient response to the intervention (odds ratio [OR], 1.97; 95% confidence interval [CI],1.09-4.28, p = .049 at 3 months; OR, 2.5; 95% CI, 1.20-6.47, p = .03 at 6 months). The median pain score decreased from 7 at baseline to 6 at both 3 and 6 months (p = .01). Morphine equivalent daily dose did not significantly change during that same period (143 mg/day vs. 139 mg/day, p = .13). CONCLUSIONS: Most patients who received the CHAT intervention improved in their NMOU behaviors and pain intensity scores 3 and 6 months post-intervention. These preliminary findings support the efficacy of CHAT in managing patients receiving opioids for cancer pain who demonstrate NMOU behavior.

Sleep disturbance in cancer patients referred to an ambulatory integrative oncology consultation.

BACKGROUND: Sleep disturbance (SD) is highly prevalent in oncology and negatively affects quality of life and mortality. Evidence supports the use of integrative oncology (IO) practices to treat SD, but there is limited published data on the characteristics of SD and factors associated with SD in IO. We determined the prevalence, severity, and factors associated with SD among cancer patients seen in an ambulatory IO consultation. METHODS: Patients with cancer referred for initial outpatient IO consultation in 2017 were eligible. Patient demographics, clinical characteristics, and patient-reported outcomes (Edmonton Symptom Assessment Scale (ESAS), Measure Yourself Concerns and Wellbeing (MYCaW), PROMIS-10) were retrospectively reviewed. RESULTS: One thousand five hundred twenty patients were included in the analysis. The majority (70%) were women with breast cancer (42%). Nine hundred seventy-one (64%) patients reported significant SD with ESAS Sleep ≥ 4, yet only 11% expressed poor sleep as their primary or secondary concern for the IO consultation. The median SD (IQR) was 5 (3,7). ESAS scores for fatigue (adjusted OR 1.16; CI 1.07-1.26, p < 0.001), pain (adjusted OR 1.07; CI 1.00-1.15, p < 0.05), hot flashes (adjusted OR 1.14; CI 1.07-1.22, p < 0.001), well-being (adjusted OR 1.33; CI 1.22-1.46, p < 0.001), and psychological distress score (anxiety and depression) (adjusted OR 1.16; CI 1.01-1.11, p < 0.01) were independently associated with SD in multivariate analysis. Acupuncture was the most frequent intervention prescribed, 175 (35%). Other modalities included oncology massage (15%), health psychology (5%), and meditation (1%). CONCLUSIONS: Although 64% of patients seeking IO consultation reported clinically significant SD, only 11% were seeking integrative approaches for managing SD. ESAS fatigue, hot flashes, well-being, and psychological symptoms were significantly associated with SD.

Oncology patients' perception of physicians who use an integrated electronic health record (EHR) during clinic visits: PRIME-EHR double-blind, randomized controlled trial.

BACKGROUND: Patients with cancer prefer and positively perceive physicians who communicate face-to-face without the use of a computer. However, the use of electronic health records (EHRs) in the examination room remains a practical necessity. On the basis of existing literature, the authors developed and tested an integration model, PRIME-EHR, that focuses on the best-practice guidelines. To their knowledge, no randomized controlled trials (RCTs) have been conducted to test the effectiveness of such models. METHODS: In this double-blind, crossover RCT, 120 eligible patients with cancer were enrolled between April 1, 2019 and February 15, 2020 at The University of Texas MD Anderson Cancer Center. The objectives were to compare patients' perceptions of physicians' skills and their overall preference after they watched 2 standardized, scripted video vignettes of physicians: 1 portraying the use of a standard EHR and the other portraying the use of a PRIME-EHR. Actors and patients were blinded to the purpose of the study. Investigators were blinded to the sequence of videos watched by the patients. Validated questionnaires to rate physicians' compassion (0 = best, 50 = worst), communication skills (14 = poor, 70 = excellent), and professionalism (4 = poor, 20 = very good) were used. RESULTS: PRIME-EHR, compared with the standard EHR, resulted in better scores for physician compassion (median score, 5 [interquartile range, 0-10] vs 12 [interquartile range, 4-25]; P = .0009), communication skills (median score, 69 [interquartile range, 63-70] vs 61 [interquartile range, 50-69]; P = .0026), and professionalism (median score, 20 [interquartile range, 18-20] vs 18 [interquartile range, 14-20]; P = .0058). The majority of patients preferred physicians who used PRIME-EHR (n = 70 [77%] vs n = 21 [23%]; P < .0001). CONCLUSIONS: The PRIME-EHR approach significantly improved patients' perceptions of and preference for the physicians. This integrated model of health care delivery has the potential to improve communication and compassion in cancer care.

Random urine drug testing among patients receiving opioid therapy for cancer pain.

BACKGROUND: There is limited information regarding the true frequency of nonmedical opioid use (NMOU) among patients receiving opioid therapy for cancer pain. Data to guide patient selection for urine drug testing (UDT) as well as the timing and frequency of ordering UDT are insufficient. This study examined the frequency of abnormal UDT among patients with cancer who underwent random UDT and their characteristics. METHODS: Demographic and clinical information for patients with cancer who underwent random UDT were retrospectively reviewed and compared with a historical cohort that underwent targeted UDT. Random UDT was ordered regardless of a patient's risk potential for NMOU. Targeted UDT was ordered on the basis of a physician's estimation of a patient's risk for NMOU. RESULTS: In all, 552 of 573 eligible patients (96%) underwent random UDT. Among these patients, 130 (24%) had 1 or more abnormal results; 38 of the 88 patients (43%) who underwent targeted UDT had 1 or more abnormal results. When marijuana was excluded, 15% of the random group and 37% of the targeted group had abnormal UDT findings (P < .001). It took a shorter time from the initial consultation to detect 1 or more abnormalities with the random test than the targeted test (median, 130 vs 274 days; P = .02). Abnormal random UDT was independently associated with younger age (P < .0001), male sex (P = .03), Cut Down, Annoyed, Guilty, and Eye Opener-Adapted to Include Drugs positivity (P = .001), and higher Edmonton Symptom Assessment System anxiety (P = .01). CONCLUSIONS: Approximately 1 in 4 patients receiving opioids for cancer pain at a supportive care clinic who underwent random UDT had 1 or more abnormalities. Random UDT detected abnormalities earlier than the targeted test. These findings suggest that random UDT is justified among patients with cancer pain.

Effects of glutamine for prevention of radiation-induced esophagitis: a double-blind placebo-controlled trial.

Purpose Acute radiation-induced esophagitis (ARIE) leads to treatment delays, decreased quality of life (QOL), and secondary adverse events such as weight loss. Grade 3 ARIE occurs in 15%-30% of patients undergoing radiotherapy to the esophagus, leading to disruption or discontinuation of treatment. The purpose of this study was to assess the effects of glutamine, a common nutritional supplement, on ARIE in patients with thoracic malignancies. Patients and methods This double-blind, placebo-controlled trial enrolled patients with advanced thoracic malignancies receiving concurrent chemotherapy/radiotherapy or radiotherapy alone, with radiation doses to the esophagus ≥45 Gy. Patients were randomized (1:1) to receive 4 g of glutamine or glycine placebo twice daily. The primary objective was to determine whether glutamine decreases the severity of ARIE in these patients. Secondary objectives included assessment of the effects of glutamine on other measures of ARIE, weight, symptom burden measure assessed by the MD Anderson Symptom Inventory (MDASI-HN) questionnaire and the toxicity profile of glutamine. Results At the time of interim analysis, 53 patients were enrolled: 27 in the glutamine arm and 26 in the placebo arm. There was no difference in the incidence of esophagitis in the first 6 weeks of radiotherapy between the glutamine and placebo arms (74% versus 68%; P = 1.00). There were no significant differences between the two arms for time to onset of esophagitis. The duration of ARIE was shorter (6.3 versus 7.1 weeks; P = 0.54) and median weight loss was lower (0.9 kg versus 2.8 kg; p = 0.83) in the glutamine arm versus the placebo arm. The groups differ significantly in core symptom severity (2.1 vs 1.5, p < .03) but not in head and neck specific symptom severity (1.2 vs 1.1, p < .60) nor in symptom interference (2.1 vs 1.7, p < .22). There was no grade 3 or higher adverse event at least possibly related to glutamine. The study was terminated for futility following interim analysis. Conclusion Oral glutamine was not associated with significant improvement in severity of ARIE, weight loss, head and neck specific symptoms or symptom interference compared with placebo in patients with advanced thoracic malignancies receiving radiotherapy to the esophagus.Clinical trial information. NCT01952847, and date of registration is September 30, 2013.

Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit: a single-centre, double-blind, parallel-group, randomised trial.

BACKGROUND: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium. METHODS: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486. FINDINGS: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h -3·6 [95% CI -5·0 to -2·2]), rotation group (n=11, -3·3 [-4·4 to -2·2]), and combination group (n=10, -3·0 [-4·6 to -1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths. INTERPRETATION: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group. FUNDING: National Institute of Nursing Research.

How to Use Methadone in an Era of an Opioid Epidemic.

OPINION STATEMENT: The opioid epidemic is one of the most important public health crises as opioid-related deaths have become a leading cause of accidental death in the USA. Various efforts have been made to understand how to safely and appropriately prescribe opioids for patients with chronic pain, including those with cancer-related pain. We find the guidelines proposed by the Expert Consensus White Paper on the use of methadone to be current, comprehensive, and practical. While methadone is a complex medication with unique pharmacokinetics and pharmacodynamics, it remains a superior choice for many patients with cancer pain given its cost and applicability in a variety of situations. Methadone should be prescribed in the context of experienced clinicians as well as an interdisciplinary team. At a critical time when preventing opioid-related deaths is a priority, we recommend implementing additional precautions for monitoring including universal screening for risk of non-medical opioid use, education on proper storage and disposal, as well as discussing a plan with patients and caregivers in the case of serious complications such as opioid overdose.

Opioids and Cancer Mortality.

OPINION STATEMENT: Opioids are the gold standard for the treatment of cancer-related pain. Preclinical studies have associated opioids with cancer progression and overall survival. In mice models, opioids have been shown to possess pro-tumor activity secondary to immunosuppression, migration of tumor cells, increased activity of vascular endothelial growth factor receptors, and angiogenesis leading to tumor progression. In contrast, opioids have also been associated with having antitumor activity by activation of apoptosis and phagocytosis. However, high-quality randomized controlled trials in humans that are focused on the association between opioids and survival in cancer patients are lacking, which underscores the importance of being cautious when interpreting the results of the preclinical studies. Cancer-related pain is complex and multifactorial and may worsen as the disease progresses leading to higher opioid utilization. Moreover, cancer pain by itself has been associated with poor survival. The survival in these advanced cancer patients taking opioids may be more likely to be associated with cancer progression and not the opioid use. Adequate treatment of cancer pain has the potential to improve quality of life and performance status, highlighting the importance of continuing to use opioids to manage pain efficiently. More research is clearly needed.

Association between tobacco use, pain expression, and coping strategies among patients with advanced cancer.

BACKGROUND: The objective of the current study was to evaluate the association between tobacco use, symptom expression, and coping strategies in patients with advanced cancer. METHODS: The authors prospectively enrolled patients with advanced cancer and collected data regarding patient demographics, cancer diagnosis, morphine equivalent daily dose, cigarette smoking status using the Behavioral Risk Factor Surveillance System, symptom expression as measured by the Edmonton Symptom Assessment System, the Cut down/Annoyed/Guilty/Eye opener alcoholism questionnaire, the Screener and Opioid Assessment for Patients with Pain-short form survey, and the Brief COPE Questionnaire. RESULTS: Among 399 patients, 195 (49%) were never-smokers, 158 (40%) were former smokers, and 46 (11%) were current smokers. The most common malignancies were gastrointestinal (21%) and breast (19%). Current smokers demonstrated significantly higher pain scores at the time of consultation compared with former or never-smokers (mean 6.4 vs 5.9 vs 5.1, respectively; P = .015), demonstrated increased morphine equivalent daily dose (median 90 mg/day vs 60 mg/day vs 50 mg/day, respectively; P = .002), were more likely to screen as positive on the Cut down/Annoyed/Guilty/Eye opener questionnaire (33% vs 24% vs 8.7%, respectively; P < .0001) and were more likely to screen as positive (≥4) on the Screener and Opioid Assessment for Patients with Pain-short form survey (74% vs 13% vs 9.3%, respectively; P < .0001). Compared with former and never-smokers, current smokers were significantly more likely to cope maladaptively with substance use (P = .02), denial (P = .007), and self-blame (P < .0001). CONCLUSIONS: Among patients with advanced cancer, current and former smokers appear to be significantly more likely to have higher pain expression and thus require higher opioid doses, and to have more risk factors for using opioids in a nonprescribed manner. The results of the current study highlight the need to provide closer monitoring and increased psychosocial support for patients with cancer who smoke while receiving chronic opioid therapy.

Practices and perceptions regarding intravenous opioid infusion and cancer pain management.

BACKGROUND: In view of the recent opioid crisis, ways to promote safe and effective opioid-related practices are needed. Faster intravenous (iv) opioid infusion rates can result in increased adverse effects and risk for nonmedical opioid use. Data on best practices regarding safe iv opioid administration for cancer pain are limited. This study examined iv opioid bolus infusion practices and perceptions about opioids in cancer pain among 4 groups of inpatient oncology nurses. METHODS: An anonymous cross-sectional survey was conducted among oncology nurses working in medical, surgical, intensive care unit (ICU), and emergency department (ED) settings. An iv opioid bolus infusion speed less than 120 seconds was considered too fast. RESULTS: The participant response rate was 59% (731 of 1234). Approximately 58%, 54%, and 58% of all nurses administered morphine, hydromorphone, and fentanyl, respectively, in less than 120 seconds. The median morphine infusion speeds were 55, 60, 60, and 85 seconds for ICU, surgical, ED, and medical unit nurses, respectively (P = .0002). The odds ratios for infusing too fast were 2.04 and 2.52 for ED (P = .039) and ICU nurses (P = .003), respectively, in comparison with medical unit nurses, and they were 0.27 and 0.18 with frequent (P = .003) and very frequent use of a timing device (P = .0001), respectively, in comparison with no use. CONCLUSIONS: More than half the nurses working in the inpatient setting reported administering iv opioids too fast. ICU nurses administered opioids the fastest. Nurses who frequently used a timing device were less likely to infuse too fast. Further research is needed to standardize and improve the safe intermittent administration of iv opioids to patients with cancer.

Concurrent use of opioids with benzodiazepines or nonbenzodiazepine sedatives among patients with cancer referred to an outpatient palliative care clinic.

BACKGROUND: The concurrent use of opioids with benzodiazepines (BZD) or nonbenzodiazepine sedatives (S) recently was found to be associated with an increased risk of overdose death compared with the use of opioids alone. In the current study, the authors examined the frequency and trend of concurrent opioid/BZD-S use and its associated risk factors among patients with cancer. METHODS: Data regarding the frequency and trend of concurrent opioid/BZD-S use were extracted for 1500 randomly selected patients referred to the outpatient palliative care clinic at The University of Texas MD Anderson Cancer Center between the calendar years of 2011 and 2016. To explore associated risk factors, the authors compared the demographic and clinical predictors of 418 patients each in the concurrent opioid/BZD-S group and opioids-only group. RESULTS: In 2011, at the time of referral to the palliative care clinic, 96 of 221 patients with cancer (43%) were prescribed concurrent opioids/BZD-S. This rate progressively declined to 67 of 217 patients (31%) by 2016 (P = .0008). Patients in the concurrent opioid/BZD-S group had a higher percentage of females (233 individuals; 55% [P = .007]) and whites (323 individuals; 77% [P = .002]), and patients reported higher scores regarding depression (P = .0001), anxiety (P ≤ .0001), drowsiness (P = .048), and worst feeling of well-being (P = .001). The morphine equivalent daily dose was significantly higher in concurrent opioid/BZD-S group (median of 67.5 mg/day [interquartile range (IQR), 30-135 mg/day] vs 60 mg/day [IQR, 30-105 mg/day]; P = .034). Multivariate analysis demonstrated that anxiety (P ≤ .0001), white race (P = .0092), and poor Eastern Cooperative Oncology Group performance status (P = .0017) were significantly associated with concurrent use. CONCLUSIONS: The concurrent use of opioids with BZD-S has declined but continues to be frequent among patients with cancer. Anxiety, white race, and poor Eastern Cooperative Oncology Group performance status were associated with its use. More research is needed to explore which medications can replace these agents.

Safe Opioid Use, Storage, and Disposal Strategies in Cancer Pain Management.

Opioids are required by a majority of patients with advanced cancer. Oncologists and palliative care clinicians are faced with the challenge of safely prescribing opioids in the current environment of an opioid crisis. Many patients with cancer use opioids unsafely, store them in unsecure locations, and do not dispose of unused opioids, leading to increased availability of these opioids for others to misuse. More than 50% of people who misuse opioids obtain the drugs from a friend or relative with or without their consent. Patient and provider education has been shown to improve safe opioid use, promote secure storage, and also increase disposal of unused opioids safely in drug take-back programs that are now widely available. This article highlights the importance of patient education and cautious opioid prescribing in patients with cancer. IMPLICATIONS FOR PRACTICE: The current opioid crisis makes it challenging to effectively manage cancer pain. Providers play a prominent role in minimizing opioid misuse. Cautious prescribing with limits enforced on the quantity of opioids prescribed, close follow-up, and consistent and frequent provision of opioid education are a must. Evidence points to the impact of patient education in promoting safety around opioid use. Most people who misuse prescription opioids obtain them from family or friends. Storing opioids in the open or not disposing of unused opioids increases the availability of these opioids for misuse by others. The importance of not sharing, always locking up, and disposing of unused and expired opioids must be highlighted as part of the opioid education that must be delivered every time that opioids are prescribed. Information about local drug take-back programs may also help increase disposal of unused opioids.

Minimally Invasive Cordotomy for Refractory Cancer Pain: A Randomized Controlled Trial.

BACKGROUND: Up to 30% of patients with cancer continue to suffer from pain despite aggressive supportive care. The present study aimed to determine whether cordotomy can improve cancer pain refractory to interdisciplinary palliative care. MATERIALS AND METHODS: In this randomized controlled trial, we recruited patients with refractory unilateral somatic pain, defined as a pain intensity (PI) ≥4, after more than three palliative care evaluations. Patients were randomized to percutaneous computed tomography-guided cordotomy or continued interdisciplinary palliative care. The primary outcome was 33% improvement in PI at 1 week after cordotomy or study enrollment as measured by the Edmonton Symptom Assessment Scale. RESULTS: Sixteen patients were enrolled (nine female, median age 58 years). Six of seven patients (85.7%) randomized to cordotomy experienced >33% reduction in PI (median preprocedure PI = 7, range 6-10; 1 week after cordotomy median PI = 1, range 0-6; p = .022). Zero of nine patients randomized to palliative care achieved a 33% reduction in PI. Seven patients (77.8%) randomized to palliative care elected to undergo cordotomy after 1 week. All of these patients experienced >33% reduction in PI (median preprocedure PI = 8, range 4-10; 1 week after cordotomy median PI = 0, range 0-1; p = .022). No patients were withdrawn from the study because of adverse effects of the intervention. CONCLUSION: These data support the use of cordotomy for pain refractory to optimal palliative care. The findings of this study justify a large-scale randomized controlled trial of percutaneous cordotomy. IMPLICATIONS FOR PRACTICE: This prospective clinical trial was designed to determine the improvement in pain intensity in patients randomized to either undergo cordotomy or comprehensive palliative care for medically refractory cancer pain. This study shows that cordotomy is effective in reducing pain for medically refractory cancer pain, and these results can be used to design a large-scale comparative randomized controlled trial that could provide the evidence needed to include cordotomy as a treatment modality in the guidelines for cancer pain management.

Opioid Prescribing in an Opioid Crisis: What Basic Skills Should an Oncologist Have Regarding Opioid Therapy?

OPINION STATEMENT: Although clinical evidence supports the use of opioids for cancer-related pain, doing so amidst the current opioid crisis remains a challenge. A proportion of opioid-related deaths in the USA are attributable to prescription opioids, which implicates health care providers as one of the major contributors. It is therefore even more important now for all clinicians to follow safe and effective opioid prescribing practices. Oncologists are often in the frontline of cancer pain management. They are encouraged to use validated tools to screen all patients receiving opioids for high risk behaviors. Those identified as high risk for potential abuse of opioids should be monitored closely. When aberrant behavior is detected, the clinician will need to openly discuss the issue and its possible implications. Oncologists may then implement measures such as limiting the dose and quantity of opioids prescribed, shortening interval between follow-ups for refills to allow for increased monitoring, setting boundaries/limitations, weaning off opioid analgesics, or/and referring to a pain or palliative medicine or drug addiction expert for co-management when necessary. These efforts may aid oncologists in safely managing cancer pain in the environment of national opioid crisis.

The Impact of an Educational Program on Patient Practices for Safe Use, Storage, and Disposal of Opioids at a Comprehensive Cancer Center.

BACKGROUND: Improper use, storage, and disposal of prescribed opioids can lead to diversion or accidental poisoning. Our previous study showed a large proportion of cancer patients have unsafe opioid practices. Our objective was to determine whether an improvement occurred in the patterns of use, storage, and disposal of opioids among cancer outpatients after the implementation of a patient educational program. PATIENTS AND METHODS: Our palliative care (PC) clinic provides every patient with educational material (EM) on safe opioid use, storage, and disposal every time they receive an opioid prescription. We prospectively assessed 300 adult cancer outpatients receiving opioids in our PC clinic, who had received the EM, and compared them with 300 patients who had not received the EM. The previously used surveys pertaining to opioid use, storage, and disposal were administered, and demographic information was collected. Sharing or losing their opioids was defined as unsafe use. RESULTS: Patients who received EM were more aware of the proper opioid disposal methods (76% vs. 28%; p ≤ .0001), less likely to share their opioids with someone else (3% vs. 8%; p = .0311), less likely to practice unsafe use of opioids (18% vs. 25%; p = .0344), and more likely to be aware the danger of their opioids when taken by others (p = .0099). Patients who received the EM were less likely to have unused medication at home (38% vs. 47%; p = .0497) and more likely to keep their medications in a safe place (hidden, 75% vs. 70%; locked, 14% vs. 10%; p = .0025). CONCLUSION: The use of EM on opioid safety for patients with advanced cancer was associated with improved patient-reported safe opioid use, storage, and disposal. The Oncologist 2017;22:115-121Implications for Practice: Prescription opioid abuse is a fast-growing epidemic that has become more prominent recently, even in the cancer pain population. A previous study reported that 26% of cancer outpatients seen in the supportive care center either lose their pain medications or share their pain medications with someone else. This study demonstrates that the implementation of an opioid educational program and distribution of educational material on opioid safety brings about an improvement in opioid storage, use, and disposal practices in patients being prescribed opioids for cancer-related pain. Our study highlights the importance of consistent and thorough opioid education at every instance in which opioids are prescribed.

A Double-Blind, Randomized, Placebo-Controlled Trial of Panax Ginseng for Cancer-Related Fatigue in Patients With Advanced Cancer.

Background: Despite the high frequency, severity, and effects of cancer-related fatigue (CRF) on the quality of life (QoL) of patients with cancer, limited treatment options are available. The primary objective of this study was to compare the effects of oral Panax ginseng extract (PG) and placebo on CRF. Secondary objectives were to determine the effects of PG on QoL, mood, and function. Methods: In this randomized, double-blind, placebo-controlled study, patients with CRF ≥4/10 on the Edmonton Symptom Assessment System (ESAS) were eligible. Based on a pilot study, we randomized patients to receive either 400 mg of standardized PG twice daily or a matching placebo for 28 days. The primary end point was change in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale from baseline to day 29. Results: Of 127 patients, 112 (88.2%) were evaluable. The mean (SD) FACIT-F subscale scores at baseline, day 15, and day 29 were 22.4 (10.1), 29.9 (10.6), and 30.1 (11.6) for PG (P<.001), and 24.0 (9.4), 30.0 (10.1), and 30.4 (11.5) for placebo (P<.001). Mean (SD) improvement in the FACIT-F subscale at day 29 was not significantly different in the PG than in the placebo group (7.5 [12.7] vs 6.5 [9.9]; P=.67). QoL, anxiety, depression, symptoms, and functional scores were not significantly different between the PG and placebo groups. Improvement in the FACIT-F subscale correlated with baseline scores (P=.0005), Hospital Anxiety and Depression Scale results (P=.032), and sex (P=.023). There were fewer any-grade toxicities in the PG versus placebo group (28/63 vs 33/64; P=.024). Conclusions: Both PG and placebo result in significant improvement in CRF. PG was not significantly superior to placebo after 4 weeks of treatment. There is no justification to recommend the use of PG for CRF. Further studies are needed. Trial Registration: ClinicalTrials.gov identifier: NCT01375114.