Risk Factors for Failure to Rescue in Myocardial Infarction after Noncardiac Surgery: A Cohort Study.

BACKGROUND: Compared to other perioperative complications, failure to rescue (i.e., death after suffering a complication) is highest after perioperative myocardial infarction (a myocardial infarction that occurs intraoperatively or within 30 days after surgery). The purpose of this study was to identify patient and surgical risk factors for failure to rescue in patients who have had a perioperative myocardial infarction. METHODS: Individuals who experienced a perioperative myocardial infarction after noncardiac surgery between 2012 and 2016 were identified from the American College of Surgeons (Chicago, Illinois) National Surgical Quality Improvement Program database. Multivariable logistic regression was used to identify risk factors for failure to rescue. Subgroup and sensitivity analyses evaluated the robustness of primary findings. RESULTS: The authors identified 1,307,884 individuals who had intermediate to high-risk noncardiac surgery. A total of 8,923 (0.68%) individuals had a perioperative myocardial infarction, of which 1,726 (19.3%) experienced failure to rescue. Strongest associations (adjusted odds ratio greater than 1.5) were age 85 yr or older (2.52 [95% CI, 2.05 to 3.09] vs. age younger than 65 yr), underweight body mass index (1.53 [95% CI, 1.17 to 2.01] vs. normal body mass index), American Society of Anesthesiologists class IV (1.76 [95% CI, 1.33 to 2.31] vs. class I or II) and class V (3.48 [95% CI, 2.20 to 5.48] vs. class I or II), and presence of: ascites (1.81 [95% CI, 1.15 to 2.87]), disseminated cancer (1.54 [95% CI, 1.18 to 2.00]), systemic inflammatory response syndrome (1.55 [95% CI, 1.26 to 1.90]), sepsis (1.75 [95% CI, 1.39 to 2.20]), septic shock (1.79 [95% CI, 1.34 to 2.37]), and dyspnea at rest (1.94 [95% CI, 1.32 to 2.86]). Patients who had emergency surgery, high-risk procedures, and postoperative complications were at higher risk of failure to rescue. CONCLUSIONS: Routinely identified patient and surgical factors predict risk of failure to rescue after perioperative myocardial infarction.

A randomized trial comparing vascular access strategies for patients receiving chemotherapy with trastuzumab for early-stage breast cancer.

PURPOSE: Trastuzumab-based chemotherapy is usually administered through either a peripherally inserted central catheter (PICC) or a totally implanted vascular access device (PORT). As the most effective type of access is unknown, a feasibility trial, prior to conducting a large pragmatic trial, was undertaken. METHODS: The trial methodology utilized the integrated consent model incorporating oral consent. Patients receiving trastuzumab-based neo/adjuvant chemotherapy for early-stage breast cancer were randomized to a PICC or PORT insertion. Feasibility was reflected through a combination of endpoints; however, the a priori definition of feasibility was > 25% of patients approached agreed to randomization and > 25% of physicians approached patients. Secondary outcomes included rates of line-associated complications such as thrombotic events requiring anticoagulation, line infections or phlebitis. RESULTS: During the study period, 4/15 (26.7%) medical oncologists approached patients about study participation. Of 59 patients approached, 56 (94.9%) agreed to randomization, 29 (51.8%) were randomized to PICC and 27 (48.2%) to PORT access. Overall, 17.2% (5/29) and 14.8% (4/27) of patients had at least one line-associated complication in the PICC and PORT arms respectively. The study was terminated early due to slow accrual. CONCLUSION: The study met its feasibility endpoints with respect to patient and physician engagement. However, the slow rate of accrual (56 patients in 2 years) means that conducting a large pragmatic trial would require additional strategies to make such a study possible. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02632435.

De-escalation of bone-modifying agents in patients with bone metastases from breast cancer: a systematic review and meta-analysis.

PURPOSE: Bone-modifying agents (BMAs) such as bisphosphonates and denosumab are usually administered every 4 weeks (standard) in patients with bone metastases from breast cancer to prevent skeletal-related events (SREs). Recent randomized controlled trials suggest every 12-week (de-escalated) dosing interval may be non-inferior. The objective of this systematic review and meta-analysis was to compare the efficacy and harms of standard with de-escalated administration of BMA's in patients with bone metastases from breast cancer. METHODS: We searched Medline, PubMed, and the Cochrane Register of Controlled Trials from 1947 to March 14, 2018 and conference abstracts from (2014-March 14, 2018) for randomized clinical trials comparing every 4-week and every 12-week dosing interval of bone-modifying agents. Using PRISMA guidelines, meta-analyses were performed using random-effects models, with findings reported as risk ratios with 95% confidence intervals (CI). RESULTS: From a total of 1311 citations, we identified 8 full-text articles and 1 abstract comprising data from 5 completed randomized clinical trials (n = 1807). Zoledronate administration every 12 weeks compared to every 4 weeks produced a summary risk ratio of 1.05 (95% CI 0.88-1.25) for patients with ≥ 1 on-study SRE indicating similar efficacy. These results did not differ whether patients had received prior intravenous bisphosphonate. De-escalation was associated with a non-statistically significant lower risk of increased creatinine (summary risk ratio 0.41 [95% CI 0.15-1.16]). Currently, there are insufficient data for pamidronate and denosumab de-escalation. CONCLUSIONS: These data are supportive of de-escalation of zoledronate from onset for patients with bone metastases from breast cancer.

A multicentre, randomized pilot trial comparing vascular access strategies for early stage breast cancer patients receiving non-trastuzumab containing chemotherapy.

PURPOSE: All vascular access strategies foradministering chemotherapy in early stage breast cancer (EBC) are associated with risks and benefits. As the most effective type of access is unknown a feasibility trial, prior to conducting a large pragmatic trial, was undertaken. METHODS: The trial methodology utilized broad eligibility criteria and the integrated consent model incorporating oral consent. EBC patients receiving non-trastuzumab-containing chemotherapy were randomized to peripheral access or central line insertion. The a priori definition of feasibility was: > 25% of patients approached agreed to randomisation and > 25% of physicians approached patients. Secondary outcomes included rates of line-associated complications. RESULTS: Of 159 patients approached, 150 (94.3%) agreed to randomisation, 77 (51.3%) were randomized to peripheral and 73 (48.7%) to central access. 6/26 (23.1%) of medical oncologists approached patients. Rates of complications per chemotherapy cycles in the peripheral vs central access groups with risk difference (RD) (95% CI) were: thrombotic events requiring anticoagulation [1 (0.3%) vs. 3 (1.0%), RD - 0.7(- 1.9,0.5)], line infections [0 (0%) vs. 1 (0.3%), RD - 0.3(- 0.9,0.3)], phlebitis [2 (0.6%) vs. 0 (0%), RD 0.3(- 0.3,0.8)], and tissue infiltrations [4 (1.1%) vs. 1 (0.3%), RD 0.8(- 0.4,2.1)]. Overall, 8.0% (6/75) and 7.7% (5/65) of patients had at least one of these complications in the peripheral and central access arms respectively [RD - 0.9(- 9.4,7.6)]. The study was terminated early due to slow accrual. CONCLUSION: While meeting its a priori feasibility criteria for patient engagement, the slow accrual means that conducting a large pragmatic trial would require overcoming the barriers to physician recruitment. TRIAL REGISTRATION: NCT02688998.

Feasibility of using a pragmatic trials model to compare two primary febrile neutropenia prophylaxis regimens (ciprofloxacin versus G-CSF) in patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer (REaCT-TC).

PURPOSE: Optimal primary febrile neutropenia (FN) prophylaxis (i.e. ciprofloxacin or granulocyte-colony stimulating factors [G-CSF]) for patients receiving docetaxel-cyclophosphamide (TC) chemotherapy is unknown. We assessed the feasibility of using a novel pragmatic comparative effectiveness trial to compare these standard-of-care options. METHODS: Early-stage breast cancer patients receiving TC chemotherapy were randomised to either ciprofloxacin or G-CSF. Trial methodology consists of broad eligibility criteria, simply-defined endpoints, integrated consent model incorporating oral consent, and web-based randomisation in the clinic. Primary feasibility endpoints included patient and physician engagement (if > 50% of patients approached agree to participate and if > 50% of physicians approached patients for the study). Secondary clinical endpoints included the following: first occurrence rates of FN, treatment-related hospitalisation, or chemotherapy dose reduction/delay/discontinuation, as well as patient satisfaction with the oral consent process. RESULTS: Of 204 patients approached, 91.2% (186/204) agreed to randomisation. Sixteen of twenty (80%) participating medical oncologists randomised patients. Median patient age was 57.7 (range 31.8-84.1). The 186 patients received 557 cycles of chemotherapy. Overall incidences of first events by patient (n = 186) were as follows: FN (18/186, 21.43%), treatment-related hospitalisation (11/186, 13.10%), chemotherapy reduction (19/186, 22.62%), chemotherapy discontinuation (16/186, 19.05%), and chemotherapy delays (5/186, 5.95%). A total of 37.77% (69/186) of patients and 12.39% (69/557) of chemotherapy cycles had at least one of these first events. Patients were highly satisfied with the oral consent process. CONCLUSION: This study met its feasibility endpoints. This model offers a means of comparing standard-of-care treatments in a practical and cost-efficient manner. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov : NCT02173262.

A prospective intervention to improve happiness and reduce burnout in oncologists.

BACKGROUND: There is a paucity of data about effective interventions to improve happiness and reduce burnout in oncologists. Benjamin Franklin developed a 13-week program of "necessary activities" or "virtues" (temperance, silence, order, resolution, frugality, industry, sincerity, justice, moderation, cleanliness, tranquility, chastity, and humility) to follow, in his attempt at self-improvement. In this pilot study, we explored whether using a modified version of this was associated with any discernable impact on physician happiness, burnout, or compliance with each of the virtues. METHODS: Self-reported happiness (Oxford happiness scores) and burnout (Abbreviated Maslach Burnout Inventory) were completed at baseline (pre-study), week 13, and 1 month after completion of the program. Each day during the 13-week program, oncologists were emailed a list of virtues to focus on and scored how they felt they were complying with them. The oncologist's spouses also assessed how they felt the oncologist was complying with the virtues. RESULTS: Thirteen physicians completed the baseline scores, 11 completed Maslach/Oxford scores at the end of the study, and 8 the 1-month post-study assessment. No significant improvements in happiness and burnout (emotional exhaustion, depersonalization, personal accomplishment) scores were observed. Statistically significant changes in self-rated virtue scores were observed for temperance (p = 0.046), order (p = 0.049), and resolution (p = 0.014). Additionally, although not reaching statistical significance, 11 of 13 virtues (excepting sincerity and chastity) assessed by spouses indicated a positive change over time. CONCLUSION: In this hypothesis generating study, daily reflection on personal virtues was not associated with any statistically significant change in happiness or burnout scores. Alternative strategies should be considered.

Postoperative shared-care for patients undergoing non-cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Collaborative ("shared-care") models of postoperative care improve outcomes in patients undergoing surgery for hip fracture. Despite being widely adopted, it is unclear if similar benefits of shared-care models exist for other at-risk surgical patient populations. Thus, we performed a systematic review to understand the impact of shared-care models. METHODS: EMBASE, MEDLINE, CINAHL, and Cochrane Central Register databases were searched for prospective studies examining an in-hospital shared-care approach to postoperative management of adult non-cardiac surgery patients. The primary outcome was a composite of in-hospital mortality and mortality of up to 30 days. Secondary outcomes were long-term mortality (> 90 days) and hospital length of stay. Tertiary outcomes included quality of life and health utility measures. Risk of bias was assessed using Cochrane Collaboration tools. RESULTS: Six thousand eight hundred and ninety-six citations were reviewed and four studies (n = 987 patients) met the inclusion criteria-two randomized-controlled trials (RCT, n = 729 patients) and two non-randomized-controlled trials (NRCT, n = 258 patients). All studies were conducted in the elective surgical setting. There was no association between shared-care and control groups for in-hospital mortality (Peto odds ratio, 1.76; 95% confidence interval [CI], 0.65 to 4.80), or hospital length of stay (mean difference, -1.41; 95% CI, -3.18 to 0.35). Reporting of other outcomes was limited. Both RCTs were judged to be at high risk of bias for blinding and both NRCTs were judged to be at moderate risk of bias for reported outcomes. CONCLUSION: Overall, there was limited high-quality evidence to evaluate the effect of postoperative shared-care. Well-designed interventional studies, perhaps targeting higher risk surgical populations, are needed. REGISTRATION: PROSPERO (CRD42018094943); registered 16 May, 2018.

Optimal vascular access strategies for patients receiving chemotherapy for early-stage breast cancer: a systematic review.

IMPORTANCE: Systemic chemotherapy can be administered either through a peripheral vein (IV), or centrally through peripherally inserted central catheter (PICC), totally implanted vascular access devices (PORTs) or tunnelled cuffed catheters. Despite the widespread use of systemic chemotherapy in patients with breast cancer, the optimal choice of vascular access is unknown. OBJECTIVE: This systematic review evaluated complication rates and patient satisfaction with different access strategies for administering neo/adjuvant chemotherapy for breast cancer. EVIDENCE REVIEWED: Ovid Medline, EMBASE and the Cochrane Central Register of Controlled Trials were searched from 1946 to September 2017. Two reviewers independently assessed each citation. The Newcastle-Ottawa scale was used to assess the quality of cohort and case-control studies. FINDINGS: Of 1584 citations identified, 15 unique studies met the pre-specified eligibility criteria. There were no randomised studies comparing types of vascular access. Reports included six single-institution retrospective cohort studies, one retrospective multi-institution cohort, one retrospective cohort database study, five prospective single-institution studies, one prospective multi-institution study and one nested case-control study. Median complication rates were infection: 6.0% PICC (2 studies) versus 2.1% PORT (8 studies); thrombosis: 8.9% PICC (2 studies) versus 2.6% PORT (9 studies); extravasation: 0 PICC (1 study) versus 0.4% PORT (4 studies) and mechanical issues: PICC 3.8% (1 study) versus 1.8% PORT (9 studies). Satisfaction/quality of life appeared high with each device. CONCLUSION: In the absence of high-quality data comparing vascular access strategies, randomised, adequately powered, prospective studies would be required to help inform clinical practice and reduce variation.

A multi-center pragmatic, randomized, feasibility trial comparing standard of care schedules of filgrastim administration for primary febrile neutropenia prophylaxis in early-stage breast cancer.

INTRODUCTION: The most effective duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer (EBC) patients is unknown. Despite significant differences in cost and toxicity, no prospective trial has been performed to optimize practice. We assessed the feasibility of using a novel pragmatic trial model to compare the most commonly used schedules of filgrastim. METHODS: Early breast cancer patients receiving chemotherapy were randomized to 5, 7, or 10 days of filgrastim as primary FN prophylaxis. The trial methodology integrated broad eligibility criteria, simply defined endpoints, an integrated consent model incorporating oral consent, and web-based randomization in the clinic. Feasibility was reflected through a combination of primary endpoints including patient and physician engagement (if > 50% of appropriate patients approached agree to participate, and if > 50% of physicians approached patients for the study). Secondary endpoints included the first occurrence rates of FN, treatment-related hospital admission, or chemotherapy dose reductions/delays/discontinuation. RESULTS: From May 2015 to August 2016, 142/149 (95.3%) patients approached agreed to participate and were randomized. Seventeen of 24 (70.8%) medical oncologists approached and randomized patients. The 142 patients received a total of 495 cycles of chemotherapy. Aggregate incidences of a first event by patient were FN (8/142, 5.6%), treatment-related hospitalization (6/142, 4.2%), chemotherapy discontinuation (7/142, 4.9%), chemotherapy delays (5/142, 3.5%), and chemotherapy dose reduction (18/142, 12.7%). Overall, 31.7% (45/142) of patients and 9.0% (45/495) of chemotherapy cycles were associated with one of these first events. CONCLUSION: This study met its feasibility endpoints. This novel pragmatic trial approach offers a means of comparing standard of care treatments in a practical and cost-effective manner. The trial will now be expanded to compare rates of FN between the three filgrastim schedules. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02428114.

Filgrastim use in patients receiving chemotherapy for early-stage breast cancer-a survey of physicians and patients.

PURPOSE: Despite its widespread use as primary febrile neutropenia (FN) prophylaxis during chemotherapy for early-stage breast cancer, the optimal duration of daily filgrastim is unknown. Using the minimum effective duration may improve patient comfort and acceptability while reducing costs. Yet, suboptimal dosing may also negatively impact patient care. A survey was performed to obtain information regarding current practices for granulocyte colony-stimulating factor (G-CSF) use. METHODS: Canadian oncologists involved in the treatment of breast cancer patients, as well as patients who had received neo/adjuvant chemotherapy for breast cancer, were surveyed. Standardized surveys were designed to collect information on perceived reasons for G-CSF use and current practices. RESULTS: The surveys were completed by 38/50 (76%) physicians and 95/97 (98%) patients. For physicians, there was variability in the choice of chemotherapy regimens that required G-CSF support, the dose of filgrastim prescribed and the number of days prescribed. The majority of physicians reported using 5 (31.6%), 7 (47.4%), or 10 (13.2%) days of therapy. Nearly half of the patients (46.3%) recalled having experienced at least one of the chemotherapy-related complications including chemotherapy delays, dose reductions, and FN. While on filgrastim, 66.3% of patients reported myalgia and bone pain. Both physicians and patients expressed interest in participating in clinical trials designed to optimize the duration of filgrastim administration. CONCLUSIONS: Significant variability in practice exists with respect to filgrastim administration. Definitive studies are therefore required to standardize and improve care, as this has the potential to impact treatment outcomes, patient quality of life, and cost savings.

Predatory Invitations from Journals: More Than Just a Nuisance?

Physicians and academic researchers are frequently targeted with spam invitations to submit manuscripts to predatory journals. This study was conducted to understand the nature and characteristics of these invitations. All spam e-mails received by an academic medical oncologist over a 3-month period were collected and categorized. Presumed predatory journal invitations were analyzed and cross-checked against Beall's list of "potential, probable, or possible predatory" journals and publishers. Invitations to submit to predatory journals were the most common single type of spam received. The Oncologist 2017;22:236-240.

Optimal primary febrile neutropenia prophylaxis for patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer: a systematic review.

BACKGROUND: Due to the high rate of febrile neutropenia (FN) with docetaxel-cyclophosphamide (DC) chemotherapy, primary FN prophylaxis is recommended. However, the optimal choice of prophylaxis [i.e., granulocyte-colony stimulating factors (G-CSF) or antibiotics] is unknown. A systematic review was performed to address this knowledge gap. METHODS: Embase, Ovid Medline, Pubmed, the Cochrane database of systematic reviews, and Cochrane register of controlled trials were searched from 1946 to April 2016 for studies evaluating primary prophylactic FN treatments in breast cancer patients receiving DC chemotherapy. Outcome measures evaluated included: incidence of FN and treatment-related hospitalizations, chemotherapy dose reduction/delays/discontinuations, and adverse events. Screening and data collection were performed by two independent reviewers. RESULTS: Of 2105 identified records, 7 studies (n = 2535) met the pre-specified eligibility criteria. Seven additional studies (n = 621) were identified from prior systematic reviews. There were 3 randomized controlled trials (RCTs) (n = 2256) and 11 retrospective studies (n = 900). Study sample sizes ranged from 30 to 982 patients (median 99.5), evaluating pegfilgrastim (n = 1274), filgrastim (n = 1758), and oral ciprofloxacin (n = 108). Given the heterogeneity of patients and study design, a narrative synthesis of results was performed. Median FN rates with and without primary prophylaxis were 6.6 % (IQR 3.9-10.6 %) and 31.3 % (IQR 25-33 %), respectively. No FN-related deaths were reported. No RCT directly compared G-CSF with antibiotic interventions. CONCLUSIONS: Primary FN prophylaxis reduces the incidence of FN. Despite considerable cost and toxicity differences between G-CSF and antibiotics, there is insufficient data to make a recommendation of one strategy over another.

A cost-utility analysis of risk model-guided versus physician's choice antiemetic prophylaxis in patients receiving chemotherapy for early-stage breast cancer: a net benefit regression approach.

PURPOSE: We assessed the cost-effectiveness of a risk model-guided (RMG) antiemetic prophylaxis strategy compared with the physician's choice (PC) strategy in patients receiving chemotherapy for early-stage breast cancer. METHODS: We conducted a cost-utility analysis based on a published randomized controlled trial of 324 patients with early-stage breast cancer undergoing chemotherapy at two Canadian cancer centers. Patients were randomized to receive their antiemetic treatments according to either predefined risk scores or the treating physician's preference. Effectiveness was measured as quality-adjusted life years (QALYs) gained. Cost and utility data were obtained from the Canadian published literature. We used generalized estimating equations to estimate the incremental cost-effectiveness ratios (ICERs) and 95% confidence intervals (CIs) over a range of willingness-to-pay values. The lower and upper bounds of the 95% CIs were used to characterize the statistical uncertainty for the cost-effectiveness estimates and construct cost-effectiveness acceptability curves. RESULTS: From the health care system's perspective, the RMG strategy was associated with greater QALYs gained (0.0016, 95% CI 0.0009, 0.0022) and higher cost ($49.19, 95% CI $24.87, $73.08) than the PC strategy, resulting in an ICER of $30,864.28 (95% CI $14,718.98, $62,789.04). At the commonly used threshold of $50,000/QALY, the probability that RMG prophylaxis is cost-effective was >94%; this probability increased with greater willingness-to-pay values. CONCLUSION: The risk-guided antiemetic prophylaxis is an economically attractive option for patients receiving chemotherapy for early-stage breast cancer. This information supports the implementation of risk prediction models to guide chemotherapy-induced nausea and vomiting prophylaxis in clinical practices.

Enhancing accrual to chemotherapy trials for patients with early stage triple-negative breast cancer: a survey of physicians and patients.

PURPOSE: The optimal chemotherapy regimen for patients with early stage triple-negative breast cancer (TNBC) remains unknown. The purpose of the study is to survey physicians and breast cancer patients about preferred chemotherapy regimens for early stage TNBC and clinical trial strategies. METHODS: A standardised online questionnaire was developed and circulated to medical oncologists known to treat breast cancer. A separate questionnaire was given to patients who had received chemotherapy for breast cancer. RESULTS: The questionnaire was completed by 41/84 medical oncologists (48.8% response rate) and 74 patients. The most commonly used neoadjuvant and adjuvant chemotherapy regimens for TNBC were dose-dense doxorubicin and cyclophosphamide (AC)-paclitaxel (P), dose-dense AC followed by weekly P and fluorouracil, epirubicin, cyclophosphamide-docetaxel (FEC-D). The majority of medical oncologists (80%) would be willing to enrol patients in trials evaluating the most effective chemotherapy regimen for TNBC. Oncologists favoured a three arm trial design comparing currently available standard of care treatments (36%) and trials of novel or non-standard of care agents 22% (9/41). Sixty percent (41/74) of patients indicated that they would be willing to be enrolled in trials evaluating various adjuvant regimens for TNBC. Both oncologists and patients were interested in novel consent approaches such as using the integrated consent model. CONCLUSION: Optimisation of chemotherapy for TNBC is an important and unmet clinical need. It is apparent that various chemotherapy regimens are used for patients with early stage TNBC. The majority of medical oncologists and patients are interested in entering trials to optimise chemotherapy choices.

Choice of study endpoint significantly impacts the results of breast cancer trials evaluating chemotherapy-induced nausea and vomiting.

Multiple endpoints can be used to evaluate chemotherapy-induced nausea and vomiting (CINV). These endpoints reflect the various combinations of vomiting, nausea and rescue antiemetic use in the acute (0-24 h), delayed (>24-120 h) and overall (0-120 h) periods after chemotherapy. As the choice of outcome measure could potentially change the interpretation of clinical trial results, we evaluated CINV rates using different endpoints on a single dataset from a prospective cohort. Data from 177 breast cancer patients receiving anthracycline and cyclophosphamide-based chemotherapy was used to calculate CINV control rates using the 15 most commonly reported CINV endpoints. As nausea remains such a significant symptom, we explored the frequency at which pharmaceutical and non-pharmaceutical company-funded studies included measures of nausea in their primary study endpoint. CINV control rates ranged from 12.5 %, 95 % (CI 7.6-17.4 %) for total control (no vomiting, no nausea and no rescue medication) in the overall period to 77.4 %, 95 % (CI 71.2-83.6 %) for no vomiting in the overall period. Similar differences were found in the acute and delayed periods. Non-pharmaceutical company-funded trials were more likely to include a measure of nausea in the primary study outcome (9/18, 50 %) than pharmaceutical-funded trials (1/12, 8.3 %). The choice of trial endpoint has an important impact on reported CINV control rates and could significantly impact on interpretation of the results. Primary endpoints of studies, including those mandated by regulatory bodies, should account for nausea to reflect patient experience. Reporting of endpoints should be more comprehensive to allow for cross-trial comparisons.

Measuring the impact of guideline-based antiemetic therapy on nausea and vomiting control in breast cancer patients with multiple risk factors.

PURPOSE: The objective of this exploratory analysis was to determine if individual patient risk factors could be used to optimize chemotherapy-induced nausea and vomiting (CINV). METHODS: Through validated risk prediction models which quantify patient risk factors, 152 patients with early-stage breast cancer scheduled to received adjuvant anthracycline-based chemotherapy were categorized as being at low (level 0) or high-risk (level 1) for CINV. Prior to the first cycle of chemotherapy, low-risk patients received ondansetron and dexamethasone, while high-risk level 1 patients also received aprepitant. For subsequent cycles, patients who experienced CINV had their antiemetics changed in a stepwise manner to level 2 (extended-duration dexamethasone) or level 3 (extended-duration dexamethasone and low-dose olanzapine). RESULTS: The study enrolled 152 patients who received 484 cycles of chemotherapy. Forty patient cycles were classified as low risk (level 0) compared to 201, 162 and 81 that were classified as high-risk levels 1, 2 and 3, respectively. Complete control of acute and delayed vomiting was comparable and was achieved in over 85 % of patients across all risk levels (p = 0.56 and p = 0.99). In contrast, complete control of acute and delayed nausea was reduced in risk levels 1 to 3 compared to level 0 (acute = 51.2, 58.0, 45.7 vs. 70.0 %; p = 0.013)-(delayed = 32.8, 45.7, 34.6 vs. 62.5 %; p < 0.001). CONCLUSIONS: Despite the addition of aprepitant, extended-duration dexamethasone and olanzapine, patients at high risk for CINV due to personal risk factors failed to achieve good nausea control.

Treatment of taxane acute pain syndrome (TAPS) in cancer patients receiving taxane-based chemotherapy-a systematic review.

BACKGROUND: Taxane acute pain syndrome (TAPS) is characterized by myalgias and arthralgias starting 1-3 days and lasting 5-7 days after taxane-based chemotherapy. Despite negatively impacting patient's quality of life, little is known about the optimal TAPS management. A systematic review of treatment strategies for TAPS across all tumor sites was performed. METHODS: Embase, Ovid MEDLINE(R), and the Cochrane Central Register of Controlled Trials were searched from 1946 to October 2014 for trials reporting the effectiveness of different treatments of TAPS in cancer patients receiving taxane-based chemotherapy. Two individuals independently screened citations and full-text articles for eligibility. Outcome measures included type of treatment and response of myalgias, arthralgias, pain, and quality of life (QoL). RESULTS: Of 1614 unique citations initially identified, five studies met the pre-specified eligibility criteria. Two were randomized placebo-controlled trials (225 patients), two were randomized open-label trials 76 patients), and one was a retrospective study (10 patients). The agents investigated included gabapentin, amifostine, glutathione, and glutamine. Study sizes ranged from 10 to 185 patients. Given the heterogeneity of study designs, a narrative synthesis of results was performed. Neither glutathione (QoL, p = 0.30, no 95 % CI reported) nor glutamine (mean improvement in average pain was 0.8 in both treatment arms, p = 0.84, no 95 % CI reported) were superior to placebo. Response to amifostine (pain response) and gabapentin (reduction in taxane-induced arthralgias and myalgias) was 36 % (95 % CI, 16-61 %) and 90 % (no 95 % CI data reported), respectively. CONCLUSIONS: Despite its prevalence in patients receiving taxane-based chemotherapies, TAPS remains poorly researched and few studies evaluate its optimal management. If the management of patients is to be improved, more prospective trials are needed.

Taxane acute pain syndrome (TAPS) in patients receiving taxane-based chemotherapy for breast cancer-a systematic review.

BACKGROUND: Taxane acute pain syndrome (TAPS) is characterized by myalgias and arthralgias starting 24-48 h after taxane-based chemotherapy and lasting for 5-7 days. Relatively little is known about its incidence and impact on quality of life. OBJECTIVES: A systematic review was conducted evaluating the incidence of TAPS in breast cancer patients receiving taxane-based chemotherapy. METHODS: Embase, Cochrane, and Ovid MEDLINE were searched from 1947 to July 2015. Data was sought from randomized controlled trials (RCTs), prospective and retrospective observational studies. Two reviewers independently screened citations and full text articles. Outcomes of interest were the incidence of TAPS and its impact on quality of life. RESULTS: Of 980 citations identified, 51 relevant studies (27,007 patients) were included. Data came from RCTs (12,357 patients), retrospective (6566 patients) and prospective observational studies (6210 patients). Study sample sizes ranged from 14 to 4149 patients (median 152). Given the significance between study heterogeneity, a meta-analysis was not performed. The incidence of TAPS varied between taxanes: paclitaxel (median 13.1 %, range 0.9-86 %), docetaxel (median 10.5 %, range 3.6-70 %), and nab-paclitaxel (26 %, range 14-43 %). In the metastatic setting, median incidence was 30 % (range 5.4-73 %), compared with 11.3 % (range 0.9-86 %) in the adjuvant setting. Three out of eight studies assessing quality of life demonstrated pain interference with daily activities. CONCLUSIONS: The incidence of TAPS varies between taxanes, regimens, and disease settings. In order to identify patients at the greatest risk of TAPS, and hence optimize its prevention and management, standardized methods of diagnosing and measuring TAPS are needed.

Management of urogenital atrophy in breast cancer patients: a systematic review of available evidence from randomized trials.

Symptoms of urogenital atrophy are common in breast cancer survivors. Its optimal management is currently unknown. A systematic review of randomized controlled trials (RCTs) evaluating treatments for urogenital atrophy in breast cancer patients was performed. EMBASE, Ovid Medline and the Cochrane Library were searched from 1946 to November 2014. Outcomes included improvements in both vaginal symptoms (e.g., dryness, pain, dyspareunia and itching) and vaginal hormone response measured by validated scales [e.g., Vaginal Health Index (VHI) and Vaginal Maturation Index (VMI)]. Of 430 unique citations identified, 4 studies (n = 196) met inclusion criteria. Interventions included pH-balanced gel, Replens(®), lidocaine, Estring(®) and Vagifem(®). Sample sizes ranged from 7 to 98 patients. Given the heterogeneity of the studies, a narrative synthesis of results was performed. One study of 98 patients suggested that vaginal pH-balanced gel (mean VHI 5.00 ± 0.816, mean VMI 51.18 ± 3.753) was more efficient than placebo (VHI 16.98 ± 3.875, p < 0.001, VMI 47.87 ± 2.728, p < 0.001) at 12 weeks in providing vaginal symptom relief. In patients who used lidocaine, 90 % had reduced dyspareunia compared to saline in a study of 46 patients. Although increased serum estradiol occurred, both Estring(®) and Vagifem(®) were shown to improve quality of life and VMI in a study of seven patients. Treatment of urogenital atrophy remains a challenging issue and there is a paucity of RCT evidence addressing this knowledge gap. It is evident that more prospective trials are needed.

Optimisation of steroid prophylaxis schedules in breast cancer patients receiving docetaxel chemotherapy-a survey of health care providers and patients.

PURPOSE: Despite the widespread use of steroid prophylaxis schedules for breast cancer patients receiving docetaxel chemotherapy, questions still exist regarding their optimal use. We surveyed health care providers and patients about their experiences with steroid prophylaxis. METHODS: Two questionnaires were developed and circulated. One was presented to health care providers (chemotherapy nurses, pharmacists and medical oncologists) involved in the treatment of breast cancer and the second to patients who had received docetaxel chemotherapy for early stage breast cancer. RESULTS: The health care providers' questionnaire was completed by 184 of 698 invitees: 92/171 (53.8 %) chemotherapy nurses, 56/284 (19.7 %) pharmacists and 36/243 (14.8 %) medical oncologists (overall response rate 26.4 %). Two steroid schedules were found to be the most commonly used: dexamethasone 8 mg BID for 6 doses, with either 3 (79 %) or 2 (11 %) doses taken before docetaxel administration. Suboptimal adherence to steroid premedication had been experienced by 98 % (177/181) of practitioners. Despite the presence of local treatment protocols in 65 % (119/183) of practitioners' institutions, 10 different strategies were commonly used when steroid premedication was taken incorrectly. The patients' questionnaire was completed by 72/87 (82.3 %) invitees. Respondents reported correctly taking their premedication 99 % (70/71) of the time. Patients felt steroids frequently caused side effects, the most common being sleep disturbance (35/72 = 49 %) and skin toxicity (16/72 = 22 %). CONCLUSION: Suboptimal adherence to steroid premedication prior to docetaxel administration is a common clinical challenge. There appears to be discordance between the practitioner and the patient experience. A single, universally accepted and used protocol for both pre- and post-medication and management when premedication is not taken as prescribed could improve adherence.