Outcomes of older adults with early-stage triple-negative breast cancer (TNBC) receiving chemotherapy: a single-institution experience.

BACKGROUND: Despite lower chemotherapy use in older triple-negative breast cancer (TNBC) patients, their outcomes match younger counterparts. We compared outcomes in early-stage TNBC patients by age receiving chemotherapy at a major cancer center with a national TNBC database. METHODS: Retrospective study using institutional data on stage I-III TNBC (ER/PR < 10%) women with neoadjuvant/adjuvant chemotherapy. Based on their ages at diagnosis, patients were stratified into four categories: ≤40, 41-59, 60-69, and ≥ 70 years. Demographic and clinical characteristics recorded included race, disease stage, ER/PR positivity, treatment regimen, lymphatic or vascular invasion (LVI), histologic grade, Ki-67 level, body mass index (BMI), and pathologic complete response (pCR) following neoadjuvant treatment and are summarized using descriptive statistics. The primary endpoints were overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS); all were estimated using the Kaplan-Meier method. Both univariate and multivariate (MV) Cox regressions were applied to evaluate the impact of important covariates on these time-to-event endpoints. RESULTS: Of the 2336 patients studied, 492 (21.1%) were ≤ 40 years old, 1239 (53.1%) were 41-59, 461 (19.7%) were 60-69, and 144 (6.2%) were ≥ 70. In the univariate regression model of OS/DFS/DDFS, age ≥ 70 was significantly associated with worse OS (p = 0.0217); other factors associated with worse OS were non-anthracycline-based chemotherapy, higher tumor stage, and neoadjuvant chemotherapy. The multivariate Cox regression model, adjusted for race and stage, showed no significant effects of age on OS; however, patients ≥ 70 years old who received non-anthracycline treatment combinations had worse DFS (hazard ratio = 0.349 vs. 1.049, p = 0.0293) and DDFS (hazard ratio = 0.317 vs. 1.016, p = 0.0251) than patients ≤ 40 years old. DFS from MV model after adjusting for age, race, and disease stage, the hazard ratio between anthracycline + taxane treatments and anthracycline + other treatments in patients ≥ 70 years old was statistically significantly lower than in patients ≤ 40 years old (hazard ratios [HRs] = 0.349 vs. 1.049, p = 0.0293). CONCLUSIONS: Our findings indicate that outcomes such as DFS are less favorable in older compared to younger patients with early-stage TNBC, primarily in those who did not receive an anthracycline based chemotherapy regimen.

Patient Engagement With Early Stage Advance Care Planning at a Comprehensive Cancer Center.

BACKGROUND: Establishing care preferences and selecting a prepared medical decision-maker (MDM) are basic components of advance care planning (ACP) and integral to treatment planning. Systematic ACP in the cancer setting is uncommon. We evaluated a systematic social work (SW)-driven process for patient selection of a prepared MDM. METHODS: We used a pre/post design, centered on SW counseling incorporated into standard-of-care practice. New patients with gynecologic malignancies were eligible if they had an available family caregiver or an established Medical Power of Attorney (MPOA). Questionnaires were completed at baseline and 3 months to ascertain MPOA document (MPOAD) completion status (primary objective) and evaluate factors associated with MPOAD completion (secondary objectives). RESULTS: Three hundred and sixty patient/caregiver dyads consented to participate. One hundred and sixteen (32%) had MPOADs at baseline. Twenty (8%) of the remaining 244 dyads completed MPOADs by 3 months. Two hundred and thirty-six patients completed the values and goals survey at both baseline and follow-up: at follow-up, care preferences were stable in 127 patients (54%), changed toward more aggressive care in 60 (25%), and toward the focus on the quality of life in 49 (21%). Correlation between the patient's values and goals and their caregiver's/MPOA's perception was very weak at baseline, improving to moderate at follow-up. Patients with MPOADs by study completion had statistically significant higher ACP Engagement scores than those without. CONCLUSION: A systematic SW-driven intervention did not engage new patients with gynecologic cancers to select and prepare MDMs. Change in care preferences was common, with caregivers' knowledge of patients' treatment preferences moderate at best.

Definitive demonstration by synthesis of genome annotation completeness.

We develop a method for completing the genetics of natural living systems by which the absence of expected future discoveries can be established. We demonstrate the method using bacteriophage øX174, the first DNA genome to be sequenced. Like many well-studied natural organisms, closely related genome sequences are available-23 Bullavirinae genomes related to øX174. Using bioinformatic tools, we first identified 315 potential open reading frames (ORFs) within the genome, including the 11 established essential genes and 82 highly conserved ORFs that have no known gene products or assigned functions. Using genome-scale design and synthesis, we made a mutant genome in which all 11 essential genes are simultaneously disrupted, leaving intact only the 82 conserved but cryptic ORFs. The resulting genome is not viable. Cell-free gene expression followed by mass spectrometry revealed only a single peptide expressed from both the cryptic ORF and wild-type genomes, suggesting a potential new gene. A second synthetic genome in which 71 conserved cryptic ORFs were simultaneously disrupted is viable but with ∼50% reduced fitness relative to the wild type. However, rather than finding any new genes, repeated evolutionary adaptation revealed a single point mutation that modulates expression of gene H, a known essential gene, and fully suppresses the fitness defect. Taken together, we conclude that the annotation of currently functional ORFs for the øX174 genome is formally complete. More broadly, we show that sequencing and bioinformatics followed by synthesis-enabled reverse genomics, proteomics, and evolutionary adaptation can definitely establish the sufficiency and completeness of natural genome annotations.

Naproxen chemoprevention promotes immune activation in Lynch syndrome colorectal mucosa.

OBJECTIVE: Patients with Lynch syndrome (LS) are at markedly increased risk for colorectal cancer. It is being increasingly recognised that the immune system plays an essential role in LS tumour development, thus making an ideal target for cancer prevention. Our objective was to evaluate the safety, assess the activity and discover novel molecular pathways involved in the activity of naproxen as primary and secondary chemoprevention in patients with LS. DESIGN: We conducted a Phase Ib, placebo-controlled, randomised clinical trial of two dose levels of naproxen sodium (440 and 220 mg) administered daily for 6 months to 80 participants with LS, and a co-clinical trial using a genetically engineered mouse model of LS and patient-derived organoids (PDOs). RESULTS: Overall, the total number of adverse events was not different across treatment arms with excellent tolerance of the intervention. The level of prostaglandin E2 in the colorectal mucosa was significantly decreased after treatment with naproxen when compared with placebo. Naproxen activated different resident immune cell types without any increase in lymphoid cellularity, and changed the expression patterns of the intestinal crypt towards epithelial differentiation and stem cell regulation. Naproxen demonstrated robust chemopreventive activity in a mouse co-clinical trial and gene expression profiles induced by naproxen in humans showed perfect discrimination of mice specimens with LS and PDOs treated with naproxen and control. CONCLUSIONS: Naproxen is a promising strategy for immune interception in LS. We have discovered naproxen-induced gene expression profiles for their potential use as predictive biomarkers of drug activity. TRIAL REGISTRATION NUMBER: gov Identifier: NCT02052908.

Palliative care education and research at US cancer centers: A national survey.

BACKGROUND: Palliative care (PC) education and research are essential to developing a skilled workforce and evidence base to support the delivery of quality cancer care. The current state of PC education and research at US cancer centers is unclear. In this national survey, the education and research programs of the National Cancer Institute (NCI)-designated and nondesignated cancer centers and the changes between 2009 and 2018 are compared. METHODS: Between April and August 2018, PC program leaders at all NCI-designated cancer centers and a random sample of nondesignated centers were sent a survey to examine the structure, processes, and outcomes of their programs on the basis of questions from a 2009 national survey. This preplanned analysis focused on education and research. RESULTS: There were 52 of 61 (85%) NCI-designated and 27 of 38 (71%) nondesignated cancer centers that responded. NCI-designated centers were more likely than nondesignated centers to have a PC fellowship program (87% vs 30%; P < .001), training for advanced practice providers (71% vs 44%; P = .03), PC research program (58% vs 15%; P < .001), peer-reviewed funding (43% vs 11%; P = .005), and philanthropic grants (41% vs 7%; P = .002). There were few significant improvements in PC education or research between 2009 and 2018 for both groups, notable exceptions include an increase in PC fellowships (38% vs 87%; P < .001) and mandatory PC rotations for medical oncology fellows (29% vs 55%; P = .02) at NCI-designated cancer centers. CONCLUSIONS: PC education and research are more developed at NCI-designated cancer centers. Despite some progress over the past decade, it is relatively slow and suboptimal.

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.

Patient-Reported Continuity of Care and Functional Safety Concerns After Inpatient Cancer Rehabilitation.

BACKGROUND: Patients with cancer have been noted to have inadequate continuity of care after discharge from hospital. We sought to assess patient-reported continuity of care and functional safety concerns after acute inpatient rehabilitation. METHODS: This was a prospective study that used cross-sectional surveys at a National Cancer Institute Comprehensive Cancer Center. All patients who were admitted to acute inpatient rehabilitation from September 5, 2018, to February 7, 2020, met the inclusion criteria, and completed two surveys (assessing continuity of care and functional safety concerns) upon discharge and 1 month after discharge were included in the study. RESULTS: A total of 198 patients completed the study, and no major concerns were reported by the patients. The greatest concern was a lack of adequate communication management among different providers, reported by only 10 (5.0%) patients. The combined fall and near-fall rate within 1 month after discharge was (25/198) 13%. Brain metastasis, a comorbidity of depression, and a history of falls were significantly associated with a higher risk of falls or near falls within 1 month after discharge. CONCLUSION: Although overall patients with cancer reported adequate continuity of care and feeling safe to function at home after acute inpatient rehabilitation, it is important to be aware that fall or near-fall events within 1 month after acute inpatient rehabilitation are associated with brain metastasis, comorbidity of depression, and a history of falls. Thus, patients with these risk factors may benefit from including more focused fall prevention education and interventions. IMPLICATIONS FOR PRACTICE: Patients with cancer often have extensive problems that require care from multiple health care providers simultaneously, and a high level of coordination is needed for adequate transition of care from the inpatient to the outpatient setting. This transition of care period is prone to inadequate continuity of care and, for older adults, a particular risk for falls. Assessment for risk of fall is also an important factor to consider when evaluating patients to continue oncology treatments. There is a gap in knowledge regarding patient-reported continuity of care and functional safety concerns after acute inpatient cancer rehabilitation.

Edmonton Symptom Assessment Scale Time Duration of Self-Completion Versus Assisted Completion in Patients with Advanced Cancer: A Randomized Comparison.

INTRODUCTION: To compare the time duration of self-completion (SC) of the Edmonton Symptom Assessment Scale (ESAS) by patients with advanced cancer (ACPs) versus assisted completion (AC) with a health care professional. MATERIALS AND METHODS: In this randomized comparison of ACPs seen in initial consultation at the outpatient Supportive Care Center at MD Anderson, ACPs who have never completed the ESAS at MD Anderson were allocated (1:1) to either SC of the ESAS form versus AC by a nurse. Time of completion was measured by the nurse using a stopwatch. Patients completed the Rapid Estimate of Adult Literacy in Medicine (REALM) test prior to administration of the ESAS. In the SC group, the nurse reviewed the responses to verify that the reported ESAS scores were correct. RESULTS: A total of 126 ACPs were enrolled (69 patients to AC and 57 to SC). Seventy-one patients were female, median age was 60 years, and median REALM score was 65. Median (interquartile range) time (in seconds) of SC was significantly less than AC (73 [42.9-89.1] vs. 109 [79.5-136.7], p < .0001). With nurse review time included, median time of SC increased to 117 seconds, which was not significantly different from AC (p = .28). Lower literacy (REALM) score and shortness of breath were significantly associated with increased completion time (p = .007). CONCLUSION: Regular use of ESAS will have minimal impact on clinical time, as it can be completed in about 1 minute and provides a concise yet comprehensive and multidimensional perspective of symptoms that affect quality of life of patients with cancer. IMPLICATIONS FOR PRACTICE: Because the Edmonton Symptom Assessment Scale can be completed in less than 2 minutes, hopefully the routine use of this simple yet comprehensive and multidimensional symptom assessment tool will be used at all medical visits in all patients with cancer so that the timely management of symptoms affecting patients' lives and treatment courses can occur, further enhancing personalized cancer care.

Combination Therapy of Physical Activity and Dexamethasone for Cancer-Related Fatigue: A Phase II Randomized Double-Blind Controlled Trial.

BACKGROUND: Despite the high frequency of cancer-related fatigue (CRF) and its debilitating effects on the quality of life of patients with advanced cancer, there are limited treatment options available. Treatments including physical activity (PA) or dexamethasone (Dex) improve CRF; however, they have lower adherence rates (PA) or long-term adverse effects (Dex). The aim of this study was to determine the feasibility of and preliminary results for the combination of PA and Dex in improving CRF. METHODS: In this phase II randomized controlled trial, patients with advanced cancer and CRF scores of ≥4/10 on the Edmonton Symptom Assessment Scale were eligible. Patients were randomized to standardized PA for 4 weeks with either 4 mg of Dex (LoDex arm) or 8 mg of Dex (HiDex arm) twice a day for 7 days. Feasibility and change in the Functional Assessment of Cancer Illness Therapy-Fatigue subscale (FACIT-F) from baseline to day 8 and day 29 (primary outcome) were assessed. Secondary outcomes included changes in fatigue dimensions (FACIT-General, Patient-Reported Outcomes Measurement Information System [PROMIS]-Fatigue). RESULTS: A total of 60 of 67 (90%) patients were evaluable. All patients were adherent to study medication. We found that 84% and 65% of patients in the LoDex arm and 96% and 68% of patients in the HiDex arm were adherent to aerobic and resistance exercise, respectively. The FACIT-F effect size in the LoDex arm was 0.90 (P<.001) and 0.92 (P<.001) and the effect size in the HiDex arm was 0.86 and 1.03 (P<.001 for both) at days 8 and 29, respectively. We found significant improvements in the Functional Assessment of Cancer Therapy-Physical (P≤.013) and the PROMIS-Fatigue (P≤.003) at days 8 and 29 in both arms. Mixed-model analysis showed a significant improvement in the FACIT-F scores at day 8 (P<.001), day 15 (P<.001), and day 29 (P=.002). Changes in the FACIT-F scores were not significantly different between patients in the 2 arms (P=.86). CONCLUSIONS: Our study found that the combination therapy of PA with Dex was feasible and resulted in the improvement of CRF. The improvement was seen for up to 3 weeks after the discontinuation of Dex. Further larger studies are justified. CLINICALTRIALS: gov identifier: NCT02491632.

The development of a nomogram to determine the frequency of elevated risk for non-medical opioid use in cancer patients.

OBJECTIVE: Non-medical opioid use (NMOU) is a growing crisis. Cancer patients at elevated risk of NMOU (+risk) are frequently underdiagnosed. The aim of this paper was to develop a nomogram to predict the probability of +risk among cancer patients receiving outpatient supportive care consultation at a comprehensive cancer center. METHOD: 3,588 consecutive patients referred to a supportive care clinic were reviewed. All patients had a diagnosis of cancer and were on opioids for pain. All patients were assessed using the Edmonton Symptom Assessment Scale (ESAS), Screener and Opioid Assessment for Patients with Pain (SOAPP-14), and CAGE-AID (Cut Down-Annoyed-Guilty-Eye Opener) questionnaires. "+risk" was defined as an SOAPP-14 score of ≥7. A nomogram was devised based on the risk factors determined by the multivariate logistic regression model to estimate the probability of +risk. RESULTS: 731/3,588 consults were +risk. +risk was significantly associated with gender, race, marital status, smoking status, depression, anxiety, financial distress, MEDD (morphine equivalent daily dose), and CAGE-AID score. The C-index was 0.8. A nomogram was developed and can be accessed at https://is.gd/soappnomogram. For example, for a male Hispanic patient, married, never smoked, with ESAS scores for depression = 3, anxiety = 3, financial distress = 7, a CAGE score of 0, and an MEDD score of 20, the total score is 9 + 9+0 + 0+6 + 10 + 23 + 0+1 = 58. A nomogram score of 58 indicates the probability of +risk of 0.1. SIGNIFICANCE OF RESULTS: We established a practical nomogram to assess the +risk. The application of a nomogram based on routinely collected clinical data can help clinicians establish patients with +risk and positively impact care planning.

State of palliative care services at US cancer centers: An updated national survey.

BACKGROUND: This study examined the changes in outpatient palliative care services at US cancer centers over the past decade. METHODS: Between April and August 2018, all National Cancer Institute (NCI)-designated cancer centers and a random sample of 1252 non-NCI-designated cancer centers were surveyed. Two surveys used previously in a 2009 national study were sent to each institution: a 22-question cancer center executive survey regarding palliative care infrastructure and attitudes toward palliative care and an 82-question palliative care program leader survey regarding detailed palliative care structures and processes. Survey findings from 2018 were compared with 2009 data from 101 cancer center executives and 96 palliative care program leaders. RESULTS: The overall response rate was 69% (140 of 203) for the cancer center executive survey and 75% (123 of 164) for the palliative care program leader survey. Among NCI-designated cancer centers, a significant increase in outpatient palliative care clinics was observed between 2009 and 2018 (59% vs 95%; odds ratio, 12.3; 95% confidence interval, 3.2-48.2; P < .001) with no significant changes in inpatient consultation teams (92% vs 90%; P = .71), palliative care units (PCUs; 26% vs 40%; P = .17), or institution-operated hospices (31% vs 18%; P = .14). Among non-NCI-designated cancer centers, there was no significant increase in outpatient palliative care clinics (22% vs 40%; P = .07), inpatient consultation teams (56% vs 68%; P = .27), PCUs (20% vs 18%; P = .76), or institution-operated hospices (42% vs 23%; P = .05). The median interval from outpatient palliative care referral to death increased significantly, particularly for NCI-designated cancer centers (90 vs 180 days; P = 0.01). CONCLUSIONS: Despite significant growth in outpatient palliative care clinics, there remain opportunities for improvement in the structures and processes of palliative care programs.

Challenging the Status Quo of Physician Attire in the Palliative Care Setting.

BACKGROUND, AIM, AND HYPOTHESIS: This randomized controlled trial aimed to compare the impact of a physician's attire on the perceptions of patients with cancer of compassion, professionalism, and physician preference. Our hypothesis was that patients would perceive the physician with formal attire as more compassionate than the physician wearing casual attire. MATERIALS AND METHODS: One hundred five adult follow-up patients with advanced cancer were randomized to watch two standardized, 3-minute video vignettes with the same script, depicting a routine physician-patient clinic encounter. Videos included a physician in formal attire with tie and buttoned-up white coat and casual attire without a tie or white coat. Actors, patients, and investigators were all blinded to the purpose and videos watched, respectively. After each video, patients completed validated questionnaires rating their perception of physician compassion, professionalism, and their overall preference for the physician. RESULTS: There were no significant differences between formal and casual attire for compassion (median [interquartile range], 25 [10-31] vs. 20 [8-27]; p = .31) and professionalism (17 [13-21] vs. 18 [14-22]; p = .42). Thirty percent of patients preferred formal attire, 31% preferred casual attire, and 38% had no preference. Subgroup analysis did not show statistically significant differences among different cohorts of age, sex, marital status, and education level. CONCLUSION: Doctors' attire did not affect the perceptions of patients with cancer of physician's level of compassion and professionalism, nor did it influence the patients' preference for their doctor or their trust and confidence in the doctor's ability to provide care. There is a need for more studies in this area of communications skills. Clinical trial identification number. NCT03168763 IMPLICATIONS FOR PRACTICE: The significance of physician attire as a means of nonverbal communication has not been well characterized. It is an important element to consider, as patient preferences vary geographically, are influenced by cultural beliefs, and may vary based on particular care settings. Previous studies consisted of nonblinded surveys and found increasing confidence in physicians wearing a professional white coat. Unfortunately, there are no randomized controlled trials, to the authors' knowledge, to confirm the survey findings. In this randomized, blinded clinical trial the researchers found that physician's attire did not affect patients' perception of the physician's level of compassion and professionalism. Attire also did not influence the patients' preferences for their doctor or their trust and confidence in the doctor's ability to provide care.

Prognostic Value of HER2 to CEP17 Ratio on Fluorescence In Situ Hybridization Ratio in Patients with Nonmetastatic HER2-Positive Inflammatory and Noninflammatory Breast Cancer Treated with Neoadjuvant Chemotherapy with or without Trastuzumab.

BACKGROUND: We previously reported that in patients with HER2-positive (HER2+) locally advanced breast cancer treated with neoadjuvant trastuzumab-containing regimens, high HER2 to centromere enumerator probe 17 ratio on fluorescence in situ hybridization (HER2 FISH ratio) was an independent predictor of high pathologic complete response (pCR) rate, which translated into improved recurrence-free survival (RFS). We sought to determine whether high HER2 FISH ratio is a predictor of pCR and prognosis in patients with HER2+ nonmetastatic inflammatory breast cancer (IBC) and non-IBC treated with neoadjuvant chemotherapy with or without trastuzumab. MATERIALS AND METHODS: This study included all patients with histologically proven stage III, HER2+ primary IBC, and non-IBC treated with neoadjuvant chemotherapy with or without trastuzumab and definitive surgery during 1999-2012. Univariate and multivariate logistic regression models were applied to assess the effect of covariates on pCR. Kaplan-Meier estimates with log-rank test were employed for survival analysis. Univariate and multivariate Cox proportional hazards models were used to assess the effect of covariates on RFS and overall survival (OS). RESULTS: The study included 555 patients with stage III, HER+ breast cancer, 181 patients with IBC, and 374 with non-IBC. In the IBC cohort, HER2 FISH ratio was not significantly associated with pCR, RFS, or OS. In the non-IBC cohort, higher HER2 FISH ratio was significantly associated with higher pCR rate and longer OS. CONCLUSION: HER2 FISH ratio showed prognostic value among patients with HER2+ non-IBC but not HER2+ IBC treated with neoadjuvant chemotherapy. This disparity may be due to the underlying aggressive nature of IBC. IMPLICATIONS FOR PRACTICE: The findings of this study indicate that the HER2 to fluorescence in situ hybridization ratio as a continuous variable has promise as a predictor of pathologic complete response to neoadjuvant chemotherapy in patients with HER2-positive (HER2+) noninflammatory breast cancer (non-IBC) regardless of the results on HER2 immunohistochemical testing. In the future, some patients with HER2+ non-IBC and a high HER2 FISH ratio might even be offered personalized treatment options, such as nonsurgical treatment.

Examination of referral criteria for outpatient palliative care among patients with advanced cancer.

BACKGROUND: An international panel achieved consensus on 9 need-based and 2 time-based major referral criteria to identify patients appropriate for outpatient palliative care referral. To better understand the operational characteristics of these criteria, we examined the proportion and timing of patients who met these referral criteria at our Supportive Care Clinic. METHODS: We retrieved data on consecutive patients with advanced cancer who were referred to our Supportive Care Clinic between January 1, 2016, and February 18, 2016. We examined the proportion of patients who met each major criteria and its timing. RESULTS: Among 200 patients (mean age 60, 53% female), the median overall survival from outpatient palliative care referral was 14 (95% confidence interval 9.2, 17.5) months. A majority (n = 170, 85%) of patients met at least 1 major criteria; specifically, 28%, 30%, 20%, and 8% met 1, 2, 3, and ≥ 4 criteria, respectively. The most commonly met need-based criteria were severe physical symptoms (n = 140, 70%), emotional symptoms (n = 36, 18%), decision-making needs (n = 26, 13%), and brain/leptomeningeal metastases (n = 25, 13%). For time-based criteria, 54 (27%) were referred within 3 months of diagnosis of advanced cancer and 63 (32%) after progression from ≥ 2 lines of palliative systemic therapy. The median duration from patient first meeting any criterion to palliative care referral was 2.4 (interquartile range 0.1, 8.6) months. CONCLUSIONS: Patients were referred early to our palliative care clinic and a vast majority (85%) of them met at least one major criteria. Standardized referral based on these criteria may facilitate even earlier referral.

Predicting survival in patients with advanced cancer in the last weeks of life: How accurate are prognostic models compared to clinicians' estimates?

BACKGROUND: It is unclear if validated prognostic scores such as the Palliative Performance Scale, Palliative Prognostic Index, and Palliative Prognostic Score are more accurate than clinician prediction of survival in patients admitted to an acute palliative care unit with only days of survival. AIM: We compared the prognostic accuracy of Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival in this setting. DESIGN: This is a pre-planned secondary analysis of a prospective study. SETTING/PARTICIPANTS: We assessed Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival at baseline. We computed their prognostic accuracy using the Concordance index and area under the receiver operating characteristics curve for 7-, 14-, and 30-day survival. RESULTS: A total of 204 patients were included with a median overall survival of 10 days (95% confidence interval: 8-11 days). The Concordance index for Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival were 0.74, 0.71, 0.70, and 0.75, respectively. The areas under the curve for these approaches were 0.82-0.87 for 30-day survival, 0.75-0.80 for 14-day survival, and 0.74-0.81 for 7-day survival. The four prognostic approaches had similar accuracies, with the exception of 7-day survival in which clinician prediction of survival was significantly more accurate than Palliative Prognostic Score (difference: 7%) and Palliative Prognostic Index (difference: 8%). CONCLUSION: In patients with advanced cancer with days of survival, clinician prediction of survival and Palliative Performance Scale alone were as accurate as Palliative Prognostic Score and Palliative Prognostic Index. These four approaches may be useful for prognostication in acute palliative care units. Our findings highlight how patient population may impact the accuracy of prognostic scores.

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.

Phase Angle and the Diagnosis of Impending Death in Patients with Advanced Cancer: Preliminary Findings.

BACKGROUND: Phase angle is a prognostic factor in patients with months of survival, but its accuracy has not been examined in patients with weeks/days of survival. We determined the association between phase angle and survival in patients with advanced cancer admitted to an acute palliative care unit (APCU). SUBJECTS, MATERIALS, AND METHODS: We prospectively assessed phase angle in consecutive patients with advanced cancer admitted to our APCU. We conducted univariate and multivariate survival analyses adjusting for established prognostic factors. Post hoc subgroup analyses examined patients with and without edema. RESULTS: Among 204 patients, the median overall survival was 10 days (95% confidence interval [CI] 8-11 days). Seventy-four (36%) did not have edema. The median phase angle was 3.7° for the entire cohort, 3.9° for the nonedematous subgroup and 3.6° for the edematous subgroup. In univariate analysis, a low phase angle was associated with decreased survival for the entire cohort (≤3° vs. >3°, median survival 7 vs. 10 days, p = .045) and the nonedematous subgroup (5 vs. 18 days, p < .001) but not the edematous subgroup (9 vs. 9 days, p = .84). In multivariate analysis, phase angle did not reach significance for the entire cohort but remained significant in the nonedematous subgroup (hazard ratio 2.46, 95% CI 1.14-5.31, p < .001). Specifically, phase angle ≤3° had an accuracy of 86% (95% CI 77%-93%) for 3-day survival in patients without edema. CONCLUSION: Phase angle had limited prognostic utility in unselected APCU patients but was significant in the nonedematous subgroup. Further studies are required to confirm these preliminary findings. IMPLICATIONS FOR PRACTICE: In this prospective study involving 204 patients with advanced cancer, phase angle as measured by bioelectric impedance analysis was a significant predictor of mortality independent of known prognostic factors in patients without edema but not patients with edema. Among patients without edema, a phase angle ≤3° had an accuracy of 86% for 3-day survival, which may inform the diagnosis of impending death and potentially end-of-life decision making.

Response to Oral Immediate-Release Opioids for Breakthrough Pain in Patients with Advanced Cancer with Adequately Controlled Background Pain.

BACKGROUND: There is limited evidence about the response of breakthrough pain (BTP) to the most commonly used oral immediate-release (IR) opioids. Our aim was to determine response rate to oral IR opioids for BTP control in patients with advanced cancer. MATERIALS AND METHODS: In this prospective study, palliative care outpatients, with advanced cancer and adequately managed background pain, were asked to complete a self-administered survey. We assessed patients' baseline demographics, pain characteristics, alcoholism (CAGE questionnaire), tobacco and substance abuse, and Edmonton Symptom Assessment Scores (ESAS). We determined the effectiveness of oral IR BTP opioids by using a 7-point Likert scale ranging from "very ineffective" to "very effective." "Effective" and "very effective" were defined a priori as a good response to IR opioids for BTP. RESULTS: Of 592 evaluable patients, 192 (32%) had background pain of ≤3 (ESAS pain scale 0-10). Among these 192 patients, 152 (79%) reported BTP, 143/152 (94%) took oral IR opioids for BTP, and 127/143 (89%) responded to a median dose of 10% of the total morphine equivalent daily dose. In univariate logistic regression analysis, younger age (odds ratio [OR], 0.94 per year; p = .008), higher ESAS scores for pain (OR, 1.32; p = .012), anxiety (OR, 1.24; p = .017), and dyspnea (OR, 1.31; p = .007) had statistically significant association with poor response to IR opioids for BTP. In multicovariate logistic regression, adjusted for age, a higher ESAS dyspnea score was significantly associated with poor response to oral IR opioids (OR, 1.44; p = .002). CONCLUSION: The vast majority of patients with advanced cancer with adequately controlled background pain reported a good response to oral IR opioids for BTP, supporting their use in clinical practice. IMPLICATIONS FOR PRACTICE: Oral immediate-release opioids are standard treatment for cancer breakthrough pain. However, information regarding treatment response to these commonly used opioids is limited. This study provides information that the vast majority of patients with advanced cancer, with adequately controlled background pain, reported good response to oral immediate release opioids for managing their breakthrough pain episodes. Results of this study support the use of conventional oral immediate release opioids that are relatively inexpensive and readily available for management of breakthrough pain in patients with advanced cancer.