Delay In Administration Of Chemotherapy Research Articles

ENDOSCOPIC DRAINAGE FOR THE MANAGEMENT OF INFECTED SUBCUTANEOUS COLLECTIONS FOLLOWING DIEP FLAP RECONSTRUCTION TECHNIQUE: A CASE REPORT

Abstract Aim The deep inferior epigastric perforator (DIEP) flap procedure is a widely accepted method for immediate breast reconstruction following skin-sparing mastectomy in breast cancer patients. While complications are infrequent, challenges may arise, including surgical wound infection, skin necrosis, seroma, or hematoma. Methods We present the case of a 68-year-old woman with multifocal infiltrating carcinoma of the right breast (T1cN0M0) who underwent DIEP flap breast reconstruction one month before presenting to the emergency room. Her symptoms included a fever of 38°C, abdominal filling in the DIEP scar region, an elevated leukocyte count (23.01 × 10E3/microL), and a C-reactive protein level of 470 mg/L. Abdominal CT revealed a collection in the infraumbilical anterior abdominal wall extending through the subcutaneous cellular tissue of both iliac fossae. The patient underwent surgical intervention, including endoscopic drainage with lavage and drain placement under direct visualization. Results Following surgery, the patient responded positively to intravenous Meropenem, with the resolution of fever and improvement in local cellulitis. She was discharged on the 6th postoperative day with both drains, removed 10 and 15 days after surgery in an outpatient setting. Conclusions In cases where immediate percutaneous drainage is not feasible, endoscopic drainage emerges as an effective strategy for managing extensive infectious collections. This technique, involving lavage, debridement, and drain placement under direct vision, eliminates the need to reopen substantial surgical wounds. Notably, this approach aids early recovery in patients undergoing active chemotherapy, preventing delays in chemotherapy administration.

Hepatitis B Reactivation without Hepatitis Is a Common Event in Adolescent/Adult Patients of Acute Lymphoblastic Leukemia with Occult Hepatitis B (OHBI) Treated on Pediatric Protocols and Warrants Prophylactic Antivirals: A Prospective Cohort Study

Introduction: Patients with occult Hepatitis B infection(OHBI) (HBsAg negative but HBcIgG &/or anti-HBs positive in the absence of immunization) are at an increased risk of Hepatitis B(HBV) reactivation while on and after chemotherapy. It can present over a spectrum ranging from asymptomatic or mild transaminitis to fatal hepatitis, affect the dose intensity of chemotherapy and compromise outcomes. The reported risk of reactivation is variable (1-24%, Yeo, 2009), and depends on the type of therapy and the method used to detect reactivation. Antiviral prophylaxis is recommended in patients with OHBI who are treated with antiCD20 monoclonal antibodies and those who undergo allogeneic stem-cell transplant, however this has not been evaluated in patients treated on pediatric-inspired ALL protocols comprising of several immunosuppressive drugs.. Methods: This was a prospective longitudinal cohort study conducted at a single tertiary care center in India between October 2017 to July 2021 (CTRI/2017/01/007747). The primary objective was to study the incidence of HBV reactivation in patients with OHBI on ALL protocol, and secondary objectives were to study the incidence of OHBI, HBV related hepatitis and its impact on chemotherapy intensity. Newly diagnosed patients with ALL/LBL, aged ≥15 years were screened for the presence of OHBI. Patients with OHBI were considered for enrollment into the prospective part of the study if they were treated on intense protocol (modified BFM-90 ALL protocol), had normal liver function tests, and no co-infection with HCV, HIV or history of HBV vaccination. Liver functions were monitored twice weekly during the induction/reinduction phase, prior to the early and delayed intensification and once every 2-3 months during the maintenance phase. HBV DNA copies by quantitative PCR (threshold for detection 20 units/ml), were measured at baseline, week 4, week 8, week 20, 32, week 48, completion of maintenance and every 3-6 months for 1 year. If a patient developed hepatitis, serum was collected for HBV DNA levels, HBsAg, HB core IgM antibody, IgM HAV antibody, IgM HEV, HCV and CMV DNA levels. HBV reactivation was defined as- either increase in serum HBV DNA level to more than 1 log higher than that of baseline or any copy numbers if it was negative at baseline. Seventy five patients with OHBI were to be studied to detect a true incidence of >10% HBV reactivation at a one-sided significance level of 5% and 90% power (Fleming's design) Results: A total of 566 patients were screened for the study, and 172(30.4% (95% C.I. (26.6-34.4)) patients were diagnosed with OHBI. 74 patients were enrolled in the prospective part of the study (Fig 1). The baseline characteristics of the study population are summarized in Table 1. HBV DNA was detectable at baseline in only 2(2.3%) patients. 51 patients (68.9%) completed all phases of treatment. The median follow-up was 21.6 months (range 0.03-53.5 months). A total of 402 HBV DNA tests were done in this cohort with an average of 5 tests per patient. HBV reactivation occurred in 5 patients ((6.7% 95% C.I.(1.03-12.47)), none of these patients developed hepatitis during HBV reactivation. In all the patients, reactivation occurred during the maintenance phase. All of these patients were started on antivirals (Entecavir). Overall 15(20.3%) patients developed hepatitis during the study period and CMV viremia was the cause for hepatitis in 4(26.7%) patients and HCV infection was the cause in 1 (6.6%) patient. Median AST, ALT during the episodes of hepatitis were 363 and 459 respectively (range AST 150-3490, range ALT 218-1950). Two(2.7%) patients had a delay in administration of chemotherapy due to hepatitis and median duration of delay was 21 days (range 18-24). Conclusion: We conclude that the risk of HBV reactivation is significant in adolescent/adult ALL patients with OHBI treated on pediatric inspired ALL protocols. HBV related hepatitis is a late event, and monitoring with liver function tests alone is not sufficient. The use of prophylactic antivirals is justified in patients with ALL.

QLTI-10. STANDARD WORK FOR ORAL CHEMOTHERAPY IMPROVES SAFETY WITHOUT INCREASING DELAYS

Abstract Purpose Oral chemotherapy in the outpatient setting does not have the same level of oversight as chemotherapies delivered in an infusion treatment area. This project aimed to create a standardized process to prescribe outpatient oral chemotherapy to improve patient safety. The primary process-measure was laboratory data review prior to ordering therapy, with primary outcome-measure being number of days between approval to administer therapy and actual administration. A secondary process-measure was documentation quality, and counterbalance-measure was delay in ordering due to lab review. METHODS A Failure Mode Effects Analysis was performed. Standard work was developed for each step of prescribing and roles and responsibilities were assigned for each step in the process. A checklist was developed within the medical record to review and document essential steps in the process allowing for greater visibility. Fifty-three patient encounters were reviewed prior to intervention and 39 post-intervention. RESULTS FMEA identified 7 high-risk points. For the primary process measure, prior to intervention, 34/53 (64%) encounters had laboratory data review prior to chemotherapy order. After intervention, 38/39 (97%). The change did not delay ordering; we observed a mean 2-day delay between laboratory data review and chemotherapy order (significant difference from zero [p = 0.001]) pre-intervention. After intervention, there was no statistically significant delay (mean -0.74 days, p = 0.376). Documentation improved after intervention; 23/53 (43%) chemotherapy encounters contained complete data pre-intervention, and 36/39 encounters (92%) post-intervention. CONCLUSIONS As part of our standardized process, we developed a new chemotherapy checklist and flowsheet in the medical record. While the fraction of patients with zero delay in chemotherapy administration after approval did not change, patient safety improved with more patients having laboratory review prior to chemotherapy order. This review did not increase delays in ordering therapy. Documentation quality also improved. Having a standard process increases patient safety while prescribing outpatient oral chemotherapy.

Impact of Physician Dual Practices on a Pediatric-Oncology Outreach-Program.

Physician dual practices (PDP) can be defined as 'doctors combining clinical work in public and private health-sector.' This study explores the impact of PDP on a long-term pediatric-oncology outreach-program between large referral hospitals in the Netherlands, Indonesia and Kenya. This cross-sectional descriptive study used a self-administered semi-structured survey. The most senior doctor from each partner site was interviewed in June 2022. The survey contained 70 closed-ended and 7 open-ended questions and took 30-45 minutes to complete. Closed-ended questions were evaluated on 2-5 point rating scales. Informed consent was acquired and respondents endorsed the final report. In the Netherlands an estimated 0-20% of senior doctors combine work in public and private-sector, while 60-80% do so in Indonesia and Kenya according to the respondents. In Indonesia and Kenya, most of doctors are involved in PDP to augment low government salaries. Impact of PDP on pediatric-oncology care is minimal in the Netherlands, but detrimental in Indonesia and Kenya: shortage of experienced doctors, limited supervision of junior staff, slow diagnostics and delays in chemotherapy administration ultimately lead to undermining of the quality of care and adverse patient outcomes. PDP adversely impact patient care at the Indonesian and Kenyan partner sites of a pediatric-oncology outreach-program. Strategies addressing PDP in resource-poor settings are required to improve treatment outcomes and survival of children with cancer.

Factors influencing treatment delays in a safety net hospital: teachable moments?

<h3>Objectives:</h3> Delays in diagnosis and treatment of ovarian cancer contribute to decreased overall survival. A post-hoc analysis of a GOG study demonstrated that initiation of chemotherapy more than 25 days after surgery adversely affected survival. Furthermore, previous studies have shown that socio-demographic factors also play a role in treatment delays. We sought to determine factors contributing to delays in treatment initiation and reasons for delay in chemotherapy administration in patients receiving primary treatment of epithelial ovarian cancer at our safety net hospital. <h3>Methods:</h3> All patients with epithelial ovarian cancer seen between 1/1/2009 and 12/1/2019 were identified. Only patients who had primary chemotherapy at our safety net hospital were included. Demographic variables included race, ethnicity, median household income (MHI), and age for patients undergoing both primary cytoreductive surgery (PCRS) and neoadjuvant chemotherapy (NACT). A delay in initiation of chemotherapy was defined as > 25 days post surgery (whether undergoing PCRS or interval cytoreduction after NACT). Time to treatment initiation (TTI) was defined as date of gynecologic oncology consult to surgery (for PCRS) or first cycle of chemotherapy (for NACT). Delays between cycles of chemotherapy were noted through chart review. Linear regression analyses were performed using demographic variables as predictors for treatment duration (with p value set at 0.05). <h3>Results:</h3> 101 patients were identified that met inclusion criteria. The median age in this cohort was 61 years (range 25-82). 18 (17.8%) were Black and 75 (74.3%) were Hispanic. 81 (80.2%) patients had a MHI less than $60,000. 63 (62.4%) patients underwent PCRS and 38 (37.6%) patients underwent NACT. 77.2% of patients did not initiate adjuvant chemotherapy until > 25 days post surgery. The median TTI in the PCRS group was 15 days; however, 53 (84.1%) patients undergoing PCRS received their first cycle of chemotherapy > 25 days post surgery. The median TTI in the NACT group was 19 days, and 25 (65.8%) patients who completed NACT received their first cycle of adjuvant chemotherapy > 25 days after surgery. Black patients undergoing PCRS experienced a 30 day longer TTI than White patients (p=0.013). TTI for patients undergoing PCRS and living in an area with a median household income < $30,000 was 42 days versus 14 days in patients living in an area with median household income >$60,000 (p=0.033). In patients greater than 65 years old undergoing NACT, the time from interval cytoreductive surgery to adjuvant chemotherapy start was longer: 27 days for patients age < 65 years versus 39 days for patients ≥65 years (p=0.005). There were 76 total delays in chemotherapy administration identified. 39 (60.9%) of these were due to medical reasons and 37 (48.6%) were due to non-medical reasons. Specifically, 5 (6.5%) were due to regimen intolerance; 11 (14.5%) were due to hospitalizations or surgeries; 15 (19.7%) were due to patient factors such as transportation; 22 (28.9%) were due to scheduling barriers; and 23 (30.1%) were due to lab abnormalities. <h3>Conclusions:</h3> Significant delays exist in initiation of treatment and completion of treatment in patients receiving first line therapy for epithelial ovarian cancer. Race, income, and age were predictors of delays in treatment. Both medical as well as non-medical factors precluded timely delivery of treatment. Future quality studies at our institution will investigate whether these changes decrease delays in cancer care.

Impact of facility-volume on achieving a textbook oncologic outcome following primary debulking surgery for advanced-stage epithelial ovarian carcinoma

<h3>Objectives:</h3> Composite outcomes have emerged as a more accurate marker of optimal oncologic care. We evaluated the impact of facility-volume on achieving a ‘textbook oncologic outcome' (TOO) among patients diagnosed with advanced stage epithelial ovarian carcinoma (EOC) undergoing primary debulking surgery (PDS) followed by adjuvant chemotherapy. <h3>Methods:</h3> Patients diagnosed between 2004-2015 with stage IIIC-IV EOC who underwent PDS at the reporting facility followed by adjuvant chemotherapy were identified in the National Cancer Database. Annual facility PDS volume was calculated and high-volume facilities were defined those performing at least 12 PDS per year. TOO was defined as achievement of complete gross resection (CGR), no 90-day mortality, no prolonged hospitalization (>10 days), no unplanned readmission within 30-days from discharge, and initiation of adjuvant chemotherapy within 42 days from surgery and evaluated among patients with available data for all variables. Median overall survival (OS) was compared with the log-rank test and a Cox multivariate model was constructed to control for confounders. <h3>Results:</h3> A total of 19875 patients were used to calculate annual PDS facility-volume. Final analysis cohort included 6984 patients with available data for all variables of interest; 14.8% were managed at a high-volume center. A TOO was achieved for 1764 (25.3%) patients. Rate of CGR was 42.8%, while rate of prolonged hospitalization was 15.2%. Unplanned re-admission (8%) and death within 90-days (1.4%) were rare, while 28.6% of patients experienced a delay in chemotherapy administration. Patients managed at high-volume centers were more likely to achieve a TOO (28.1% vs 24.8%, p=0.022). After controlling for age, race, insurance, and comorbidities, PDS at a high-volume center was associated with a higher likelihood of achieving a TOO (OR: 1.17, 95% CI: 1.01, 1.36). Median OS of patients who did and did not achieve a TOO was 58.45 and 42.51 months respectively, p<0.001. After controlling for histology, stage, comorbidities, patient age, race, and type of insurance, TOO was associated with better survival (HR: 0.64, 95% CI: 0.59, 0.70). <h3>Conclusions:</h3> PDS at a high-volume center was associated with superior oncologic outcomes for patients with advanced-stage EOC. Centralization of care of these patients to centers of excellence should be considered.

Clinical Outcomes of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia in a County Hospital System

BackgroundMajor advances in the treatment of acute lymphoblastic leukemia (ALL) over the past decade have resulted in 5-year overall survival (OS) rates of 80% in mature B cell ALL, 50% in precursor B cell ALL, 50% to 60% in T cell ALL, and 60% to 70% in Philadelphia chromosome–positive (Ph+) ALL, as reported in studies from large, specialized centers. However, many patients treated in the community have limited access to novel therapies and stem cell transplantation (HSCT). Patients and MethodsThe purpose of this retrospective cohort analysis was to evaluate the clinical outcomes of patients ≥ 16 years with newly diagnosed ALL treated from October 2007 to June 2019 in the Harris County Health System, Houston, TX. ResultsOne hundred forty-six patients were included, with newly diagnosed pre-B-ALL (n = 127), T-ALL (n = 18), and chronic myeloid leukemia and/or lymphoid blast crisis (n = 1). Median age was 35 years (16-82) at diagnosis, and 81(55%) were male. The majority of patients with pre-B ALL identified as Hispanic (n = 118, or 92%). Ninety-eight (67%) of patients were uninsured or indigent, receiving care under the county's financial assistance programs. Hyper-CVAD-based induction chemotherapy was administered in 134 (92%) of patients, while 9 (6%) were treated on different protocols, and 3 (2%) were not treated due to early death, or patient refusal. Imatinib was the most common TKI used in 17 of 30 or 57% of patients with Ph+ disease. Out of 137 evaluable for response patients, 117 (85%) achieved complete remission (CR + CRi), 19 (14%) had refractory disease, and 1 (1%) died within 4 weeks of diagnosis. Median follow-up time was 50 months (1.5-135). For the entire study cohort, the median duration of CR/CRi was 15.4 months. Out of 62 patients who were eligible for consolidative HSCT at first CR, 52 (89%) did not receive it, with lack of insurance being the most common reason (n = 29, or 56%). Barriers to utilization of novel therapies such as blinatumomab or CAR-T were also observed. Patient-caused delays in administration of chemotherapy and treatment interruptions of at least 30 days were seen in 31(23%) patients. At 1, 2, and 5 years, relapse rates were 37%, 56%, and 70%. Recurrent and/or refractory disease was the cause of death in most patients (n = 69 [85%]). Five-year EFS and OS rates were 22% and 38% for patients with pre-B ALL, 24% and 44% for patients with T ALL, and 13% and 27% for patients with Ph+ ALL. Median OS was significantly increased (not reached [NR] vs. 24 months; P = .00088) in patients with an indication for HSCT in first CR due to high-risk features who underwent HSCT, versus those who did not. ConclusionAddressing barriers raised by socioeconomic disparities, increasing access to effective therapies, and including patients with ALL treated in the community in clinical trials may improve survival for underserved populations.

Dietary Antioxidant Micronutrient Intake and Toxicity during Remission Induction in Children with Acute Lymphoblastic Leukemia (ALL): Results from Dana-Farber Cancer Institute (DFCI) ALL Consortium Trial 05-001

Introduction: Treatment related toxicities are a major contributor to morbidity during induction therapy in childhood ALL. Our prior study in 103 children with ALL suggested that low intakes of antioxidant micronutrients were associated with toxicity and delays in chemotherapy administration (Am J Clin Nutr 79:1029, 2004). The objective of this study was to examine whether inadequate antioxidant micronutrient dietary intake in children with ALL is associated with episodes of infection or ≥grade 3 mucositis during Remission Induction.Methods: Assessment of dietary intake was collected in patients (pts) ages 1-17.9 years enrolled on the DFCI ALL Consortium Protocol 05-001 from 2005-2011. Institutional review board approval was obtained by each of the 9 participating centers. Grade 3 or higher (NCI CTCAEvs) mucositis, culture positive bacteremia and fungemia, and radiographic invasive fungal disease were prospectively collected. Dietary intake was assessed with the Harvard Service Food Frequency Questionnaire (FFQ) for children ages 1-5 years and the Youth and Adolescent Harvard FFQ for children ages 5-18 years and queried about intake in the past 30 days at the end of induction. Dietary antioxidant intake from food sources ± supplementation was examined by comparing consumption above and below recommended intake for age and sex as per the Dietary Reference Intake (DRI). Micronutrient intake was summarized with descriptive statistics and plotted by the presence/absence of a given toxicity in induction. Categorical and continuous variables were compared between group with the Fisher's exact test and the Wilcoxon rank sum test respectively. Logistic regression was used to model the probability of a given toxicity univariately and with a multivariable adjustment for sex and age.Results: Among 794 eligible pts, 561 (71%) had analyzable FFQs. The sample with dietary surveys responses was marginally younger (p=0.06) and more often classified as initial standard risk (p=0.01) than those with no end of induction survey. DRI recommendations were not met for vitamin C (18%), vitamin E (67%) and zinc (12%); 39% of pts reported zinc overconsumption. 141 (25%) of pts with dietary data had ≥1 bacterial and/or fungal infection, 131 (23%) had ≥1 bacterial infection, and 19 (3%) had ≥1 fungal infection. 24 (4%) pts experienced at least 1 event of ≥grade 3 mucositis. Female sex was associated with overall and bacterial infection (p=0.02) and marginally with mucositis (p=0.06). The proportion of patients with ≥Grade 3 mucositis was marginally higher (p=0.06) for those not meeting the vitamin C recommendation (OR=2.3; 95% CI 1.0-5.5), but was not significant (p=0.10) in a multivariable model. Supplementation was reported by 88 (16%) for zinc, vitamins C, E, and A in combination, 16 (3%) for β-carotene and total carotene, and 87 (15%) for vitamin E alone. Intake levels of vitamins C, E, and A, zinc and total carotenoids from food sources and total (food + supplementation) were compared for pts with and without infection and mucositis (unadjusted for age/sex) (Figure 1). Bacterial infection was associated with low intake from food only of zinc (p=0.02), vitamin A (p=0.01), and vitamin E (p=0.049). Mucositis was associated with the following: low intakes of vitamin C from food (p=0.04), vitamin E from food (p=0.03), total lycopene (p=0.03), total α-carotene (p=0.01), total β-carotene (p=0.007) and from food (p=0.008), total carotene (p=0.005) and carotene from food (p=0.006), and total vitamin A (p=0.01) and vitamin A from food (p=0.004). Females age <10 had higher rates of bacterial infection with low β-carotene (p=0.05) and vitamin A from food (p=0.004). In males age ≥10, low vitamin E from food was observed in those with bacterial infections (p=0.05). Supplementation did not confer an added benefit for most nutrients.Conclusions: Confirming our pilot study, data from a large prospective cohort show that low dietary intakes of antioxidant vitamins, carotenoids and zinc primarily from food sources predict risk for bacterial infection or mucositis during induction therapy for childhood ALL. Dietary supplementation for most vitamins and minerals did not confer an added benefit for prevention of infection or mucositis over levels obtained from food. Our results suggest a possible modifiable dietary intervention to reduce toxicity during induction therapy for ALL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Surgery as a Viable Option in Neutropenic Appendicitis.

A major clinical challenge in the care of children with cancer is how to take care of those patients with chemotherapy-induced neutropenia who develop acute appendicitis. How do we weigh the risk of perforation and sepsis against the risk of surgery in these high-risk patients? In this issue of Pediatrics, Many et al1 report a 7-year retrospective review across 15 North American pediatric tertiary-level institutions comparing management strategies and outcomes for 66 children with neutropenia and image-confirmed acute appendicitis. The authors found that those who undergo appendectomy within 24 hours of diagnosis have fewer postoperative complications, shorter length of stay, and fewer delays in chemotherapy compared with those who are initially treated nonoperatively, with the worst outcomes occurring among children with a delayed appendectomy during the admission.1 Although the sample size of this study is relatively small, the authors have amassed the largest study to date to evaluate the management of acute appendicitis in children with neutropenia. A notable strength is that the subjects are similar across treatment groups by factors such as age and important clinical characteristics including malignancy type, symptom duration, maximum temperature, and absolute neutrophil count.In this report, the authors also describe significant practice variability in the rate of upfront appendectomy across institutions (0%–100%). There was also likely heterogeneity across different institutions in the antibiotic choice, duration, and resistance patterns in those managed nonoperatively; we are thus unclear as to how this may have influenced outcomes. The hemodynamic status and degree of systemic sepsis of the patients at the time of diagnosis is not reported and we cannot know (a limitation of a retrospective study of this kind) whether this influenced the choice of management strategy. Also unknown is the impact, if any, of the administration of granulocyte colony-stimulating factor in the 29 patients to whom it was given. Assuming count recovery occurred more frequently in this subpopulation, did that influence outcomes in any way? In this review, those with count recovery who subsequently underwent appendectomy were not analyzed separately from those who had failure of nonoperative management, so we are unable to determine if this subgroup fared better nor if there is any benefit to waiting on count recovery if the outcomes are ultimately equivalent or better. It is also interesting that the majority of patients in this study who successfully completed initial nonoperative management went on to require no further treatment (75%). Prospectively acquired long-term outcomes data comparing this subgroup to those who underwent upfront appendectomy may add strength to the argument for initial surgery.Concerns about operative interventions in patients with neutropenia have been largely focused on wound and infectious complications. Consistent with smaller studies, the authors provide additional evidence that timely appendectomy should be the priority in these patients.2,3Although the authors demonstrate delays in chemotherapy administration among those patients treated nonoperatively, the immediate and long-term effects on oncologic outcomes of these delays are unknown. Given that these children were all receiving chemotherapy and became neutropenic as a result, these likely represent interruptions in treatment as opposed to delays in initiation. Studies in which authors have examined the effects of delays in chemotherapy on oncologic outcomes have been largely focused on delays in initiation, and even among these studies, the data are mixed with some researchers suggesting no effect.4,5 The clinical relevance of the interruptions in treatment shown by the authors is therefore unknown.Nevertheless, we congratulate the authors on tackling an important question on surgery in neutropenic appendicitis. They have nicely laid the groundwork for a potential algorithm for the management of acute appendicitis in children with neutropenia, in which upfront appendectomy can be safely offered and may likely be preferred in those patients most likely to benefit. Decreases in hospital length of stay, postoperative complications, and, as a result, cost of care in this particularly vulnerable population can only serve to improve the overall quality of care that they receive.

Chemotherapy Wait Times in a Network of Pediatric Oncology Clinics.

Patient satisfaction with medical care delivery is an important aspect of value-based health care. Providers strive to provide optimal patient satisfaction. Among a network of ambulatory pediatric oncology affiliate clinics, we conducted patient satisfaction surveys and found that the lowest scores were related to delays in the administration of chemotherapy. To address this shortcoming, we used continuous improvement methodologies to reduce the delay in chemotherapy administration in 3 affiliate clinics. To evaluate the efficacy of the quality improvement interventions implemented at each affiliate clinic, we measured the time from patient arrival to the start of chemotherapy administration over a 2-week period before and after the interventions. Wait times for chemotherapy administration were reduced in each clinic by 7% to 15%, exceeding the preestablished goal of a 5% reduction without affecting patient safety. Patient satisfaction for chemotherapy wait times was also marginally increased. In conclusion, implementation of quality improvement interventions across a clinical network can improve specific aspects of patient satisfaction, thereby improving the overall patient experience.

The clinical utility of baseline cardiac assessments prior to adjuvant anthracycline chemotherapy in breast cancer: a systematic review and meta-analysis.

Cardiac assessment with multi-gated acquisition scan (MUGA) or echocardiography (ECHO) is commonly employed prior to adjuvant anthracycline-based chemotherapy (AA). However, the clinical utility of routine baseline cardiac assessments prior to AA for early-stage breast cancer (EBC) is unknown. To determine: (i) the clinical utility of routine baseline cardiac assessments prior to AA for EBC and (ii) identify patients in whom baseline cardiac assessments may not be warranted. A systematic review of the literature was conducted to identify all relevant studies that met predefined criteria. The clinical utility was defined by: (i) the rates of abnormal baseline left ventricular ejection fraction (LVEF) and (ii) the rates of change in chemotherapy decisions prompted by baseline LVEF results. Eight studies met our criteria, of whom six (n = 2545) reported rates of abnormal LVEF and six (n = 1713) reported rates of change in chemotherapy decision. Overall, 2.5% (95% CI 2.0-4.0%) of patients had abnormal baseline LVEF and 1.6% (95% CI 1.0-3.0%) had a change in chemotherapy decision. In subset analyses, the underlying imaging modality (ECHO vs. MUGA) or inclusion of patients with metastatic disease (YES vs. NO) did not significantly affect these rates. There were no consistently identified underlying predictors of abnormal baseline LVEF across studies. Routine baseline cardiac assessments prior to AA in all EBC patients have low yield and infrequently affect clinical management. Future studies should further examine potential predictors of abnormal cardiac functions in an attempt to identify low risk patients in whom routine baseline LVEF assessment may not be warranted and prevent delay in chemotherapy administration.

Clinical audit to assess delays in chemotherapy administration at daycare oncology center at a tertiary care hospital in Karachi, Pakistan.

There were delays reported by patients in chemotherapy administration in daycare oncology. Therefore, we decided to audit all processes which are involved in chemotherapy administration. The objective was to improve our service by decreasing the time between admission and initiation of chemotherapy and identify the reasons for delays. The audit was conducted in three parts. In Review I, audit tool was developed and information documented of 109 patients receiving chemotherapy at daycare center from April 14 to May 13, 2015. Five processes were assessed out of which delay in initial assessment by the nurse was the only factor identified leading to delay in chemotherapy. Review II was done from March 1 to 31, 2016 of 208 patients after increasing the number of nurses and Review III from June 7 to August 25, 2016 of 287 patients by dividing the initial assessment process at two different areas to decrease delay in initial assessment. Seventy-two percent of patients had their initial assessment done within 15 min of arrival in daycare in the first audit. In the second part of audit this percentage decreased to 55%, and finally, in the third part of the audit, percentage was improved and increased to 75% after separating initial assessment process into two areas (P < 0.001, Kruskal-Wallis test). After separating initial assessment process into two different areas, delays in chemotherapy administration were reduced.

Toxicity of (neo)adjuvant chemotherapy for BRCA1- and BRCA2-associated breast cancer.

Treatment with (neo)adjuvant chemotherapy for breast cancer, as currently given, causes cell damage by induction of double-strand DNA breaks. Because BRCA1 and BRCA2 proteins play a role in the repair of DNA damage, the efficacy of (neo)adjuvant chemotherapy may be increased in BRCA1/2-associated breast cancer patients. As a downside, acute chemotherapy-related toxicity may also be increased. We selected all female patients who were treated at the Erasmus MC Cancer Institute, with (neo)adjuvant chemotherapy for primary or locoregional recurrence of breast cancer (PBC/LR) between January 1, 2004 and December 31, 2014. The primary outcome was the relative total dose intensity (RTDI), calculated for anthracyclines and taxanes separately. Secondary outcomes were the occurrence of febrile neutropenia, delay in chemotherapy administration, and switch to another chemotherapy regimen due to toxicity. In total, 701 patients treated for PBC/LR were eligible for data analyses, among which 85 BRCA1/2 mutation carriers (n = 67 BRCA1 and n = 18 BRCA2). The mean RTDI for anthracyclines was not significantly different between both groups (98.7 % in the BRCA1/2, 96.6 % in the sporadic group, p = 0.27). Also the mean RTDI for taxanes was not significantly different between the groups (93.6 % in the BRCA1/2-associated, 90.0 % in the sporadic group, p = 0.12). Linear regression analysis revealed no significant effect of BRCA1/2 mutation carriership on the RTDIs. No significant differences were found in the percentages of patients presenting with febrile neutropenia, having a delay in chemotherapy administration or switching to an altered chemotherapy regimen. Additionally, the odds ratios showed no significant effect of BRCA1/2 mutation carriership on the secondary outcome variables. (Neo)adjuvant chemotherapy-related toxicity was not different between BRCA1/2-associated and sporadic breast cancer patients suggesting that the DNA damage repair mechanism of non-cancer cells with only one normal copy of either the BRCA1 or BRCA2 gene is sufficiently functional to handle acute chemotherapy-associated toxicity.

Innovation in chemotherapy administration process.

This project was started after patient's complaints of increased cost burden on patients with increase stay of patient in hospital for chemotherapy administration for 3-4 days, how to decrease this hospital stay and financial burden and how can we improve services to decrease hospital stay and expedite the process of chemotherapy administration. A total of 100 patients' confidential files reviewed from February 12, 2013 to May 15, 2013, patients, who were admitted for chemotherapy administration only in inpatient area and all services timings, were reviewed and documented on sheet named as delays chemotherapy sheet, nine processes timings checked against their benchmarks. All services process timings analyzed and compared with their benchmarks, results of all services timings are nearly close to benchmark except lab test results of patients who were admitted without labs test for chemotherapy administration delays seen in collecting blood sample and sending this sample to the laboratory, significant delay is seen in chemotherapy order entry by physician if patient is admitted after 4 p.m. for chemotherapy administration. Delays also identified in administration of chemotherapy. After identifying the reasons of delays in chemotherapy administration, improvement and innovation in chemotherapy administration process done which not only decrease hospital stay, but also decrease the cost of chemotherapy administration.

Integrative Approach Successfully Improves Safety of in-Patient Chemotherapy and Reduces Health Care Costs

IntroductionPatients with hematological malignancies often require inpatient chemotherapy treatment to administer continuous infusion of chemotherapy drugs and allow better monitoring. Inpatient setting includes multiple caregivers with different level of expertise - physicians, nursing staff, pharmacy and administrators. Many patients are seen by their hematologist in an outpatient clinic where the chemotherapy plan is written. The patient is then admitted to the inpatient floor for therapy. However in many hospitals there are 2 different electronic medical record systems that don't necessarily communicate properly. In addition, the inpatient setting utilizes more health care resources and is undoubtedly more expensive than the ambulatory care. In this paper we describe an integrative process of establishing safer and better care to hematological patients admitted for inpatient chemotherapy.MethodsA multidisciplinary team was established incorporating physicians, nurses, pharmacists and IT. We conducted focused observations and mapped the process. Failure Mode Effect Analysis (FMEA) was preformed to identify the most important issues needing intervention. An integrated electronic medical record interface was generated to enable online streaming of communication between different entities in the hospital - inpatient floor, outpatient clinic and pharmacy. We established a dedicated time out of the process. To assess the impact of our work we reviewed charts of randomly selected 18 patients who received inpatient chemotherapy prior to the interventions and continued to monitor records post intervention for the following indicators: 1. Percent of patients who received pre-chemo medications and fluids as prescribed by the hematologist; 2. The difference between a patient's weight on the chemotherapy orders and the actual patient weight as measured on admission; 3. The time difference variability between the planned administration time and the actual administration time of chemotherapy drugs.ResultsPrior to intervention, 20% of the pre-chemotherapy orders such as anti-emetics or fluids were not done according to the hematologist's request. Following the intervention, 100% of pre-chemotherapy orders were preformed accurately and timely. In 24% of patients' cases there was more than 10% difference between the weight used for chemotherapy orders and weight on admission. No significant difference was noted following intervention. In 50% of cases there was more than 2 hrs delay in chemotherapy administration on the following day. Following intervention there was no incidence of more than 2 hrs delay in chemotherapy administration. These interventions resulted in a significant decrease in hospital stay (7.4 vs. 4.7 days).ConclusionsThe Multidisciplinary team's approach is critical in a complex process as inpatient chemotherapy administration. FMEA is an essential tool to assess the severity of different failures of a complex process to prioritize interventions. Integrated electronic medical records interface helps improving communication between different providers and results in a better and safer patient care as well as reduces health care costs. DisclosuresNo relevant conflicts of interest to declare.

Abstract P1-15-21: Safety of eribulin mesylate and concomitant palliative radiotherapy for metastatic breast cancer: A single-center experience

Abstract Background. Eribulin mesylate is a recently approved new therapeutic option for patients with metastatic breast cancer (BC). It is a structurally simplified synthetic analogue of halichondrin B that inhibits the growth phase of microtubule dynamics and sequesters tubulin into non-productive aggregates, inhibiting microtubule polymerization, and inducing irreversible mitotic block at G2-M phases and apoptosis. Three phase II trials of eribulin in chemotherapy pretreated advanced BC patients were completed. In all these studies, eribulin showed a manageable tolerability profile, with most of the common drug-related adverse events being neutropenia, fatigue, alopecia, nausea, and anemia, according to the phase I trials findings. Eribulin was also associated with an overall low incidence of peripheral neuropathy. When new chemotherapy options become available, one of the most important questions regarding the sequence of treatments is to address the safety of concomitant radiation treatments. Recently has been reported a clinical case treated with eribulin mesylate and whole-brain radiotherapy (RT) in a heavily pretreated patient with multiple visceral and bone metastases from triple negative breast cancer. In our knowledge this is the first analysis focusing on the safety of eribulin in patients concomitantly treated with palliative RT. Methods. All patients where heavily pretreated for metastatic breast cancer (≥4 previous chemotherapy lines), including anthracyclines and taxanes-based regimens. Patients received eribulin mesylate (1.4 mg/m2 i. v., on days 1 and 8, of a 21-day cycle). Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST), every 8 weeks, or sooner if disease progression was suspected. Safety was assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Measures of bone-pain scores and analgesic consumption were evaluated at each visit, using a patient-rated scoring system. Results. Concerning 25 consecutive treated patients, median performance status at baseline was 2 (range 1-3). A median of 4 cycles of eribulin (range 2-10) were administered. All patients received palliative bone RT during eribulin treatment. No suspension or delay in chemotherapy administration was necessary. 20/25 cases underwent spinal bone irradiation; 8 Gy in single fraction was given in 13/25 patients, 12 cases received 20 Gy in 5 fractions. The overall response rate was 24% and the clinical benefit rate was 40%. Toxicity was manageable and in line with main published series; the most frequent grade 3 hematologic adverse events were neutropenia (56%), and anemia (20%). Bone pain scores fell within a few weeks and remained below baseline value throughout the analysis. The mean pain score was 2 at baseline and 0.7 at the end of observation period. The mean analgesic score was 1.8 at baseline and 1.6 at the end of follow-up. Conclusions. Our clinical practice experience supports the evidence that eribulin has clinical activity and is characterized by a manageable safety profile, also when combined to palliative RT. Concomitant treatment is feasible also in patients heavily pretreated, and with poor performance status. Citation Format: Icro Meattini, Vieri Scotti, Carla De Luca Cardillo, Beatrice Detti, Vanessa Di Cataldo, Lorenzo Livi. Safety of eribulin mesylate and concomitant palliative radiotherapy for metastatic breast cancer: A single-center experience [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-21.

Delay in chemotherapy administration impacts survival in elderly patients with epithelial ovarian cancer

ObjectivesThe objective of this study was to characterize chemotherapy treatment patterns in elderly patients with epithelial ovarian cancer (EOC) and their impact on overall survival (OS). MethodsWe identified patients age ≥65years with stage II–IV EOC who underwent cytoreduction from 2003 to 2011. Relevant clinical variables were extracted and correlated with OS. Statistical analyses were performed using logistic regression, Kaplan–Meier methods, and multivariable Cox proportional hazard models. ResultsOne hundred and eighty-four patients were included in the analysis. The average age was 73years with American Society of Anesthesiology Physical Status Class 2 or 3. Approximately 78% underwent primary debulking surgery (PDS). OS for the entire cohort was 3.3years. One hundred and fifty-seven patients received adjuvant chemotherapy, of which 70% received initial platinum-based doublet therapy; 67.5% of patients were able to complete the intended six cycles of chemotherapy; of these, 34% experienced a dose reduction and 45% experienced one or more dose delays. Any dose delay was associated with a decrease in overall survival (p=0.02) and remained significant even after controlling for age, stage, and residual disease and number of chemotherapy cycles received (p=0.029). ConclusionsElderly EOC patients frequently required chemotherapy dose reductions and delays in chemotherapy administration. Multivariate analysis confirmed that dose delays are an independent factor associated with decreased OS.

Delay in chemotherapy administration adversely affects overall survival in elderly ovarian cancer patients

Objectives: Elderly patients with ovarian cancer represent a vulnerable population that frequently demonstrates poor outcomes. In this study, we sought to evaluate the impact of treatment modification (dose delays and reduction) on overall survival in the elderly as well as to characterize treatment patterns in this population and how they relate to overall survival (OS).

Safety of Biosimilar Filgrastim in Patients with Haematological Malignancies Undergoing Neutropenia-Inducing Chemotherapy: A Subanalysis of the Next Study

IntroductionFebrile neutropenia (FN) is a major risk factor for infection-related morbidity/mortality as well as a dose-limiting toxicity in patients (pts) undergoing chemotherapy (CT). Biosimilar filgrastim (Nivestim™, Hospira Inc.) is a granulocyte-colony stimulating factor (G-CSF) licensed for the treatment of neutropenia and FN induced by myelosuppressive CT. The NEXT (Nivestim™ safety profile in patiEnts treated with cytotoXic CT in real-life clinical pracTice) study aimed to assess the safety of biosimilar filgrastim in pts undergoing CT for malignancies.MethodsThe NEXT study was a prospective, observational, non-interventional, longitudinal, national, multicentre study conducted in France. The primary objective was to evaluate the safety of biosimilar filgrastim by gathering adverse event (AE) data. Adult pts (n=2114) undergoing cytotoxic CT for malignancies (excluding chronic myeloproliferative and myelodysplastic syndrome) and receiving biosimilar filgrastim as prophylaxis, or as curative treatment, were included. Data collected included pt characteristics, biosimilar filgrastim treatment-related data and treatment emergent AEs, including FN. Pts were monitored for 1–6 CT cycles at three visits: inclusion, a follow-up visit during treatment and the final visit following CT. Here we present data for pts with haematological malignancies.ResultsOf the pts analysed, 525 had haematological malignancies (chronic lymphoid leukaemia [CLL]/acute lymphoid leukaemia [ALL]: 70; lymphoma: 408; myeloma: 47). Overall, the mean age ± standard deviation (SD) of pts with haematological malignancies was 64.8 ± 15.4 years (64.4% male). At inclusion, 88.0% of pts had no prior FN (CLL/ALL: 88.6%; lymphoma: 89.2%; myeloma: 76.6%); 31.1% had prior CT (CLL/ALL: 32.9%; lymphoma: 27.5%; myeloma: 59.6%) and 27.1% had prior G-CSF therapy (CLL/ALL: 21.4%; lymphoma: 26.7%; myeloma: 38.3%). Of the pts prescribed a prior G-CSF therapy, 39.2% received biosimilar filgrastim. The majority of pts (98.9%) received biosimilar filgrastim prophylactically (CLL/ALL: 100.0%; lymphoma: 98.8%; myeloma: 97.9%).Of the group receiving biosimilar filgrastim with curative intent, the median time to initiation of biosimilar filgrastim therapy was 14.0 days after the start of the last CT cycle (lymphoma: 14.0 days; myeloma: 14.0 days); mean treatment duration ± SD was 4.8 ± 1.6 days (lymphoma: 5.2 ± 1.5 days; myeloma: 3.0 ± 0.0 days). In this group, 50.0% of pts received a dose of 30 MIU (lymphoma: 40.0%; myeloma: 100.0%) and biosimilar filgrastim was administered subcutaneously in all pts.In the prophylactic biosimilar filgrastim group, the median time to initiation of biosimilar filgrastim was 6 days after start of the last CT cycle (CLL/ALL: 6.0 days; lymphoma: 6.0 days; myeloma: 6.5 days); mean treatment duration ± SD was 6.7 ± 4.6 days (CLL/ALL: 7.5 ± 7.0 days; lymphoma: 6.6 ± 4.0 days; myeloma: 5.9 ± 4.5 days). In this group, 70.9% of pts received a dose of 30 MIU (CLL/ALL: 57.1%; lymphoma: 72.5%; myeloma: 78.3%) and biosimilar filgrastim was administered subcutaneously in all pts. Anti-infective prophylaxis was reported in 51.2% of pts (CLL/ALL: 88.6%; lymphoma: 42.9%; myeloma: 67.4%). In the prophylactic group, 7.5% (95% confidence interval [CI] 5.5, 10.1) experienced FN (CLL/ALL: 7.1% [2.7, 16.0]; lymphoma: 7.1% [4.9, 10.1]; myeloma: 10.9% [4.3, 23.5]).Of the pts with haematological malignancies, 18.6% experienced ≥1 AE (CLL/ALL: 8.6%; lymphoma: 21.5%; myeloma: 8.5%). The most common AEs (>5.0% of pts) were bone/muscular disorders (total: 13.7% [CLL/ALL: 7.1%, lymphoma: 16.0% myeloma: 4.3%]) and muscle pain (total: 13.4% [CLL/ALL: 7.1%, lymphoma: 15.5% myeloma: 4.3%]). In this analysis, 7.5% of pts were hospitalised for FN and/or infection (CLL/ALL: 7.1%; lymphoma: 7.1%; myeloma: 10.9%). The mean duration of hospitalisation ± SD for FN and/or infection after the first CT cycle was 11.3 ± 16.2 days (CLL/ALL: 10.5 ± 6.4 days; lymphoma: 11.4 ± 17.4 days; myeloma: 0.0 ± 0.0 days), 3.4% of pts had a CT dose reduction (CLL/ALL: 2.1%; lymphoma: 2.8%; myeloma: 2.3%) and 7.7% of pts (CLL/ALL: 15.7%; lymphoma: 5.9%; myeloma: 11.4%) had a delay in administration of CT due to FN and/or infection.ConclusionBiosimilar filgrastim was effective and well-tolerated in pts undergoing CT for haematological malignancies and is an alternative therapeutic option for pts with CT-induced neutropenia. DisclosuresMaloisel:Pfizer: Research Funding; Novartis: Research Funding; Hospira: Research Funding; Amgen: Research Funding. Albrand:Hospira: Employment.

A single-institution analysis of the utility of pre-induction ejection fraction measurement in patients newly diagnosed with acute myeloid leukemia

Anthracyclines, a standard component of induction therapy for acute myeloid leukemia (AML) are known to be cardiotoxic. Existing evidence supporting routine baseline pre-induction cardiac function testing is limited. We conducted a retrospective analysis of 119 consecutive patients diagnosed with AML at our center from 2009 to 2012. In the 76 patients for whom induction chemotherapy was planned, baseline ejection fraction measurements were rarely abnormal (four cases), and in none of these abnormal cases did the result change management decisions. Awaiting LVEF evaluation results led to a delay in chemotherapy administration by a mean of approximately 2 days at significant additional costs to the healthcare system. Routine baseline ejection fraction measurement should be abandoned as it does not change management, results in treatment delay and unnecessary healthcare expenditures. More selective baseline testing, preferentially in patients in whom there is a clinical reason of cardiac disease, should be pursued.