Cancer-related cognitive impairment in patients with non-central nervous system malignancies: an overview for oncology providers from the MASCC Neurological Complications Study Group.

Cancer-related cognitive impairment (CRCI) is commonly experienced by individuals with non-central nervous system cancers throughout the disease and treatment trajectory. CRCI can have a substantial impact on the functional ability and quality of life of patients and their families. To mitigate the impact, oncology providers must know how to identify, assess, and educate patients and caregivers. The objective of this review is to provide oncology clinicians with an overview of CRCI in the context of adults with non-central nervous system cancers, with a particular focus on current approaches in its identification, assessment, and management.

Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field.

Ten-Year Trends in Antiemetic Prescribing in Patients Receiving Highly Emetogenic Chemotherapy.

Purpose: Prevention of chemotherapy-induced nausea and vomiting is essential to preserve quality of life in patients with cancer receiving highly emetogenic chemotherapy (HEC). Recently, new drugs (eg, fosaprepitant, and the newer neurokinin-1 receptor antagonists [NK1RAs] rolapitant and netupitant) and updated antiemetic guidelines have emerged. However, trends in real-world antiemetic use are understudied. Methods: We identified patients treated with an initial dose of HEC (either cisplatin or doxorubicin/cyclophosphamide) from January 2006 to June 2016 using administrative claims data from a US commercial insurance database (OptumLabs). Antiemetic use was determined by identifying intravenous/oral/transdermal administration within ±1 day of the chemotherapy dose and/or prescription fill from 14 days before to 7 days after chemotherapy. We used descriptive statistics to present patient demographics, chemotherapy drugs administered, presence/absence of a central intravenous access device, and antiemetics used. Results: A total of 23,030 patients (67.3%) received doxorubicin/cyclophosphamide and 11,206 (32.7%) received cisplatin. Dexamethasone and 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs) were consistently used by 85% to 95% of patients, consistent with guideline recommendations. NK1RAs were underused early on, but use increased to approximately 80% in the most recently evaluated year. Fosaprepitant use increased precipitously starting in 2009, preceding a sharp decrease in aprepitant use beginning in 2011. Receipt of olanzapine, rolapitant, and netupitant was minimal throughout the study period. Conclusions: Dexamethasone and 5-HT3RAs were used by most patients receiving HEC, in accordance with guideline recommendations. NK1RA use was less adherent with guidelines.

Carba NP as a simpler, rapid, cost-effective, and a more sensitive alternative to other phenotypic tests for detection of carbapenem resistance in routine diagnostic laboratories.

PURPOSE: Resistance to carbapenems due to carbapenemases has been increasingly noticed in Enterobacteriaceae. Clinical and Laboratory Standards Institute (CLSI) has recommended the latest Carba NP (CNP) test as a confirmatory test for carbapenemase production in Enterobacteriaceae. Low sensitivity of disk diffusion (DD) and modified Hodge test (MHT) may result in missing out of resistant strains which can adversely affect clinical management. The present study compares three phenotypic tests - CNP test, DD, and MHT for detection of carbapenemase production. MATERIALS AND METHODS: Four hundred consecutive, nonduplicate Enterobacteriaceae isolates were tested for carbapenem resistance using ertapenem disc (10 µg) by Kirby-Bauer DD method, MHT, and CNP. These tests were performed and interpreted as per the CLSI standards. CNP was considered to be the reference test for comparison. Sensitivity, specificity, and accuracy rates for ertapenem DD and MHT were calculated. RESULTS: One hundred and six out of 400 strains were positive by CNP test. Of the 294 CNP-negative strains, 28 were resistant by DD and 18 were resistant by MHT. Of the 106 CNP-positive strains, 82 were resistant and 16 were intermediate by DD while 76 were positive by MHT ertapenem DD had a sensitivity and specificity of 66.04% and 90.48%, respectively. Sensitivity and specificity of MHT were 54.72% and 93.88%, respectively. There was considerable discordance between all the three tests. CONCLUSION: As a rapid, simple, and cost-effective test with a greater capability greater to detect carbapenemase producers, CNP can be implemented in routine diagnostic laboratories, thereby benefiting patient care and antimicrobial stewardship.

Hope, Symptoms, and Palliative Care.

BACKGROUND: Hope is important to patients with cancer. Identifying factors that influence hope is important. Anxiety, depression, fatigue, and pain are reported to impair hope. The objective of this study was to determine whether age, gender, marital status, duration of cancer, symptoms, or symptom burden measured by the sum of severity scores on the Edmonton Symptom Assessment Scale (ESAS) correlated with hope measured by the Herth Hope Index (HHI). METHODS: Patients with advanced cancer in a palliative care unit participated. Demographics including age, gender, marital status, cancer site, and duration of cancer were collected. Individuals completed the ESAS and HHI. Spearman correlation and linear regression were used to assess associations adjusting for gender (male vs female), age (< 65 vs ≥ 65 years), marital status (married or living with a partner vs other), and duration of cancer (≤ 12 vs > 12 months). RESULTS: One hundred and ninety-seven were participated in the study, of which 55% were female with a mean age of 61 years (standard deviation 11). Hope was not associated with gender, age, marital status, or duration of cancer. In univariable analysis, hope inversely correlated with ESAS score (-0.28), lack of appetite (-0.22), shortness of breath (-0.17), depression (-0.39), anxiety (-0.32), and lack of well-being (-0.33); only depression was clinically relevant. In multivariable analysis, total symptom burden weakly correlated with hope; only depression remained clinically significant. DISCUSSION: This study found correlation between symptom burden and hope was not clinically relevant but was so for depression. CONCLUSION: Among 9 ESAS symptoms, only depression had a clinically relevant correlation with hope.

Allogeneic hematopoietic stem cell transplant in adult patients with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes.

MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative. We describe transplant outcomes of 43 patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median follow-up of 21 months, overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML without BT and 47%, 40%, and 34% respectively in CMML with BT. Higher HSCT-comorbidity index (HSCT-CI >3 versus ≤3; p = 0.015) and splenomegaly (p = 0.006) predicted worse OS in CMML without BT. In CMML with BT, engraftment failure (p = 0.006) and higher HSCT-CI (p = 0.03) were associated with inferior OS, while HSCT within 1-year of diagnosis was associated with improved OS (p = 0.045). In MDS/MPN,U, at median follow-up of 15 months, OS, CIR, and NRM were 62%, 30%, and 14%, respectively.

Can pregabalin prevent paclitaxel-associated neuropathy?--An ACCRU pilot trial.

PURPOSE: Paclitaxel can cause an acute pain syndrome (P-APS), considered to be an acute form of neuropathy and chronic chemotherapy-induced peripheral neuropathy (CIPN). Anecdotal reports suggested that gabapentin may be helpful in the prevention of these toxicities. The purpose of this pilot study was to obtain data to support or refute the utility of pregabalin for the prevention of P-APS and CIPN. METHODS: Patients scheduled to receive weekly paclitaxel (80 mg/m(2)/dose) were randomized 1:1 to receive pregabalin 75 mg or a placebo, twice daily, during the 12 weeks of chemotherapy. Patients completed the European Organization of Research and Treatment of Cancer Quality of Life (EORTC QLQ) CIPN20 questionnaire at baseline, prior to each dose of paclitaxel and monthly for 6 months post-treatment. Patients completed a post-paclitaxel questionnaire for 6 days after each dose of paclitaxel and an acute pain syndrome symptom questionnaire on day 8. The primary end point was to determine the effect of pregabalin on the maximum of the worst acute pain scores for the week following paclitaxel administration for cycle 1. RESULTS: Forty-six patients were randomly assigned to the treatment or placebo arm. There was no suggestion of a difference between the two study arms with regard to P-APS measures. While there was a suggestion that pregabalin decreased numbness, there was no suggestion that it decreased tingling, pain, or the EORTC QLQ-CIPN20 subscale scores. There were no evident toxicity differences between the two study arms. CONCLUSIONS: The results of this pilot trial do not support that pregabalin is helpful for preventing P-APS or paclitaxel-associated CIPN.

Use of non-opioid analgesics as adjuvants to opioid analgesia for cancer pain management in an inpatient palliative unit: does this improve pain control and reduce opioid requirements?

BACKGROUND: Cancer pain is complex, and despite the introduction of the WHO cancer pain ladder, few studies have looked at the prevalence of adjuvant medication use in an inpatient palliative medicine unit. In this study, we evaluate the use of adjuvant pain medications in patients admitted to an inpatient palliative care unit and whether their use affects pain scores or opiate dosing. METHODS: In this retrospective observational study, patients admitted to the inpatient palliative care unit over a 3-month period with a diagnosis of cancer on opioid therapy were selected. Data pertaining to demographics, diagnosis, oral morphine dose equivalent of the opioid at the time of discharge, adjuvant analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and pain scores as reported by nurses and physicians were collected. RESULTS: Seventy-seven patients were eligible over a 3-month period, out of which 65 (84 %) were taking an adjuvant medication. The most commonly prescribed adjuvant was gabapentin (70 %). Fifty-seven percent were taking more than one adjuvant. There were more women in the group receiving adjuvants (57 vs. 17%, p = 0.010). Those without adjuvants compared with those on adjuvants did not have worse pain scores on discharge as reported by physicians (0.8 ± 0.8 vs. 1.0 ± 0.7, p = 0.58) or nurses (2.0 ± 2.7 vs. 2.1 ± 2.6, p = 0.86). There was no difference in morphine equivalent doses of the opioid in both groups (median (min, max); 112 (58, 504) vs. 200 (30, 5,040)) at the time of discharge; 75-80 % of patients had improvement in pain scores as measured by a two-point reduction in numerical rating scale (NRS). DISCUSSION: This study shows that adjuvant medications are commonly used for treating pain in patients with cancer. More than half of study population were on two adjuvants or an adjuvant plus NSAID along with an opioid. We did not demonstrate any benefit in terms of improved pain scores or opioid doses with adjuvants, but this could reflect confounding variables and physician choice. Larger prospective studies are needed to define the opioid-sparing effects of adjuvants. CONCLUSION: Adjuvant agents are used in over 80 % of those treated for cancer pain.

Relationship of ethnicity and CD4 Count with glucose metabolism among HIV patients on Highly-Active Antiretroviral Therapy (HAART).

BACKGROUND: HIV patients on HAART are prone to metabolic abnormalities, including insulin resistance, lipodystrophy and diabetes. This study purports to investigate the relationship of ethnicity and CD4+ T cell count attained after stable highly-active antiretroviral treatment (HAART) with glucose metabolism in hyperrtriglyceridemic HIV patients without a history of diabetes. METHODS: Demographic, anthropometric, clinical, endocrinologic, energy expenditure and metabolic measures were obtained in 199 multiethnic, healthy but hypertriglyceridemic HIV-infected patients [46% Hispanic, 17% African-American, 37% Non-Hispanic White (NHW)] on stable HAART without a history of diabetes. The relationship of glucose and insulin responses to ethnicity, CD4 strata (low (<300/cc) or moderate-to-high (≥ 300/cc)), and their interaction was determined. RESULTS: African-Americans had significantly greater impairment of glucose tolerance (P < 0.05) and HbA1c levels (P < .001) than either Hispanics or NHWs. In multivariate models, after adjusting for confounders (age, sex, HIV/HAART duration, smoking, obesity, glucose, insulin and lipids), African-Americans and Hispanics had significantly higher HbA1c and 2-hour glucose levels than NHW's. Demonstrating a significant interaction between ethnicity and CD4 count (P = 0.023), African Americans with CD4 <300/cc and Hispanics with CD4 ≥300/cc had the most impaired glucose response following oral glucose challenge. CONCLUSIONS: Among hypertriglyceridemic HIV patients on HAART, African-Americans and Hispanics are at increased risk of developing diabetes. Ethnicity also interacts with CD4+ T cell count attained on stable HAART to affect post-challenge glycemic response.

Higher parity and shorter breastfeeding duration: association with triple-negative phenotype of breast cancer.

BACKGROUND: The combination of increased parity and shorter breastfeeding duration might increase the odds of the least differentiated triple-negative breast cancer (BC) phenotype, theoretically because an expanded progenitor cell population from each pregnancy would incompletely differentiate postpartum. METHODS: Subjects consisted of a consecutive case series of 2473 women treated for invasive breast cancer between 2001 and 2006. Breast cancer phenotype (triple-negative BC, vs non-triple-negative BC) was compared with reproductive and demographic information. Odds ratios (OR) with 95% confidence intervals (CIs) for the association of breastfeeding duration (months per child) and parity with triple-negative BC were calculated after adjusting for ethnicity, age at menarche, family history, and age at diagnosis. RESULTS: Compared with non-triple-negative BC, triple-negative BC was associated with shorter duration of breastfeeding per child (OR, 0.93; 95% CI, 0.90-0.97) and with higher parity (OR, 1.12; 95% CI, 1.06-1.20). By using multivariate logistic regression, triple-negative BC was independently associated with higher parity (OR, 2.76 [95% CI, 1.86-4.08] if ≥3 live births; OR, 1.89 [95% CI, 1.30-2.74] if ≤2 live births vs nulliparae), breastfeeding duration (OR, 0.55 [95% CI, 0.41-0.74] if >2 mo/child and OR, 0.58 [95% CI, 0.42-0.82] if ≤2 mo/child vs none), African American ethnicity (OR, 2.10; 95% CI, 1.52-2.92), and younger age at diagnosis (OR, 3.02 [95% CI, 2.03-4.47] if ≤40 years vs >60 years). CONCLUSIONS: Among women with invasive breast cancer, higher parity and the absence or short duration of breastfeeding were independently associated with triple-negative BC. Any duration of breastfeeding was found to be associated with lower probability of triple-negative BC, and the odds of this phenotype decreased with increasing duration of breastfeeding.