COVID-19 and Cancer Center Operations: Lessons Learned From the NCCN Best Practices Committee.

The NCCN Best Practices Committee, which is composed of senior physician, nursing, and administrative leaders from NCCN Member Institutions, evaluated the status of cancer center operations after 1 year of operating during the COVID-19 pandemic. Two major initiatives stood out: the increase in the utilization of network sites, and the gains made in telemedicine operations and reimbursement. Experts from NCCN Member Institutions participated in a webinar series in June 2021 to share their experiences, knowledge, and thoughts on these topics and discuss the impact on the future of cancer care.

Safety and feasibility of outpatient high-dose cytarabine and intermediate-dose cytarabine for consolidation therapy in acute myeloid leukemia.

INTRODUCTION: The standard of care consolidation therapy for acute myeloid leukemia is high-dose cytarabine or intermediate-dose cytarabine, which are traditionally given inpatient. At Moffitt Cancer Center, we have moved the administration of high-dose cytarabine and intermediate-dose cytarabine to the outpatient setting through the inpatient/outpatient program. To facilitate outpatient administration, high-dose cytarabine and intermediate-dose cytarabine are given in a shorter interval of every 10 h instead of 12 h. The safety of a shorter duration interval of high-dose cytarabine and intermediate-dose cytarabine is unknown. This study aims to assess the safety and feasibility of administering high-dose cytarabine and intermediate-dose cytarabine consolidation therapy in the inpatient/outpatient setting. METHODS: This is a retrospective chart review to analyze acute myeloid leukemia patients treated with inpatient/outpatient high-dose cytarabine or intermediate-dose cytarabine consolidation therapy at Moffitt Cancer Center from January 1, 2015, through November 1, 2018. The primary objective was to determine the incidence of hospitalization during the inpatient/outpatient administration of high-dose cytarabine or intermediate-dose cytarabine. RESULTS: Two hundred fifty-three of 255 cycles of high-dose cytarabine/intermediate-dose cytarabine were delivered outpatient over the reviewed time period to 118 patients. No patients receiving outpatient high-dose cytarabine/intermediate-dose cytarabine consolidation required hospitalization during chemotherapy. Our incidence of hospitalization (24%) after chemotherapy is consistent with the reported literature. Through the inpatient/outpatient administration of high-dose cytarabine and intermediate-dose cytarabine, 1265 inpatient days were saved with an approximate revenue of $3,135,176 generated in our study period. CONCLUSION: Inpatient/outpatient administration of high-dose cytarabine and intermediate-dose cytarabine is both safe and feasible. Moving high-dose cytarabine/intermediate-dose cytarabine administration to the outpatient setting resulted in significant additional revenue vs. inpatient administration.

Safety and financial analysis of outpatient dose-adjusted EPOCH for B-cell lymphoma at a tertiary comprehensive cancer center.

INTRODUCTION: Dose-adjusted (DA-) EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) is a front-line treatment option for aggressive B-cell lymphomas. Due to regimen complexity, inpatient administration of DA-EPOCH has been historically required. Moffitt Cancer Center (MCC) developed an Inpatient/Outpatient (IPOP) program to facilitate administration of complicated regimens in the outpatient setting. We hypothesized that outpatient administration of DA-EPOCH at a comprehensive cancer center is both safe and cost-effective. METHODS: We conducted a single-center, retrospective chart review including B-cell lymphoma patients who were 18 years or older and who had received DA-EPOCH at MCC from April 26, 2017 through August 10, 2019. The primary endpoint was hospital admissions during outpatient chemotherapy administration. Additional safety endpoints included hospitalizations between cycles, infectious complications, extravasations, drug spills, pump-malfunctions, and drug-related adverse events. Financial analysis included drug cost, resource utilization, and impact of hospital bed backfill. RESULTS: 56 patients received 219 cycles of DA-EPOCH with 193 cycles administered outpatient. Zero patients required hospitalization during outpatient administration of DA-EPOCH, resulting in 965 saved hospital days. 23 patients (41%) were hospitalized between cycles, most commonly due to neutropenic fever (52%). No extravasations were documented throughout the study period. There were few incidences of drug spills or pump malfunctions. Based on current regimen utilization, the annual transition of 84 cycles of DA-EPOCH to the outpatient setting has a positive impact on margin of $1,444,548. CONCLUSIONS: Routine outpatient administration of DA-EPOCH is both safe and feasible with a positive annual impact on margin of $1,444,548 at a comprehensive cancer center.

Creative Strategies Implemented During the Coronavirus Pandemic That Will Impact the Future of Cancer Care.

The coronavirus pandemic has significantly impacted operations at leading cancer centers across the United States. In the midst of the chaos, at least one silver lining has emerged: the development of new, creative strategies for delivering cancer care that are likely to continue post pandemic. The NCCN Best Practices Committee, which is composed of senior physician, nursing, and administrative leaders at NCCN Member Institutions, conducted a webinar series in June 2020 highlighting the most promising and effective strategies to date. Experts from NCCN Member Institutions participated in the series to share their experiences, knowledge, and thoughts about the future of cancer care.

Safety at the Time of the COVID-19 Pandemic: How to Keep our Oncology Patients and Healthcare Workers Safe.

The novel coronavirus, SARS-CoV-2, was first detected as a respiratory illness in December 2019 in Wuhan City, China. Since then, coronavirus disease 2019 (COVID-19) has impacted every aspect of our lives worldwide. In a time when terms such as social distancing and flattening the curve have become a part of our vernacular, it is essential that we understand what measures can be implemented to protect our patients and healthcare workers. Undoubtedly, healthcare providers have had to rapidly alter care delivery models while simultaneously acknowledging the crucial unknowns of how these changes may affect clinical outcomes. This special feature reviews strategies on how to mitigate transmission of COVID-19 in an effort to reduce morbidity and mortality associated with the disease for patients with cancer without infection, for patients with cancer with COVID-19 infection, and for the healthcare workers caring for them, while continuing to provide the best possible cancer care. [Editor's Note: This article includes the most current information available at time of publication; however, recommendations regarding public safety and practice may change rapidly in this situation. Individuals should get the most up to date information from the CDC website.].

How I treat newly diagnosed acute myeloid leukemia in an outpatient setting: a multidisciplinary team perspective.

Historically, patients with acute myeloid leukemia received intensive chemotherapy requiring hospitalization, which can diminish quality of life and increase healthcare costs. The introduction of new therapies facilitated a shift toward outpatient therapy, which requires coordination of a multidisciplinary team, thorough patient evaluation, careful preparation and rigorous patient monitoring. Many patients are candidates for multiple treatment approaches; we generally employ CPX-351 (Vyxeos®) as an intensive outpatient approach and venetoclax (Venclyxto/Venclexta®) plus hypomethylating agents as a lower-intensity approach, with 2-3 visits/week during treatment. Treatment infusions are scheduled in the morning to leave sufficient time for transfusions and other supportive care later the same day, to prevent additional visits. With careful planning and patient monitoring, acute myeloid leukemia treatment can be successfully administered in the outpatient setting.

Bone marrow cellularity at day 14 is the most important predictive factor for response in patients with AML who require double-induction chemotherapy: Analysis from a large, single institution experience.

In patients with acute myeloid leukemia (AML), the presence of residual disease at day 14 after primary induction therapy warrants consideration of a second induction cycle. However, data to guide retreatment decisions in such patients are presently limited. Here, we retrospectively reviewed data from 176 patients with AML treated at our institution with a second induction chemotherapy regimen because of day 14 residual disease. Clinical variables and nadir bone marrow features were assessed for correlations with complete remission (CR) and overall survival (OS). In our patient group, 59% achieved CR after a second induction course. Median OS for the entire group was 12.40 months (95% CI, 9.90-14.90) but 19.07 months (95% CI, 13.13-25.01) for those who attained a CR. Nadir marrow hypocellularity (P < 0.001) at day 14, absolute blast reduction of >50% (P = 0.030), and de novo disease status (P = 0.018) were significantly correlated with CR achievement after re-induction. Marrow hypocellularity at day 14 was the most significant predictor of CR on multivariate analysis (P < 0.001). Nadir marrow features did not independently correlate with OS when accounting for CR status. Re-induction was successful in achieving CR in most patients. Study patients who did not achieve CR were more likely to have nonhypocellular marrows.

Using Vignettes to Measure and Encourage Adherence to Clinical Pathways in a Quality-Based Oncology Network: An Early Report on the Moffitt Oncology Network Initiative.

INTRODUCTION: The Moffitt Oncology Network (MON) Initiative demonstrates a way to form a value-based network based upon clinical pathways across a broad geographical area. METHODS: Moffitt Cancer Center (MCC) has developed various cancer-specific pathways. MCC pathways translate evidence-based guidelines into personalized cancer treatment and set a care standard for evaluation and personalized treatment. MCC is using these pathways with other hospital systems and physician groups throughout the MON. Clinical Performance and Value Vignettes, which are virtual patient cases related to the specific clinical pathways, are used to improve the uptake of pathways in the MON. We report here on the baseline data of 66 breast cancer care providers who took 132 breast cancer vignettes. Using the vignettes, variation in care practice is examined, with special attention to use of clinical breast cancer pathways. RESULTS: Pathway-based clinical care was measured at baseline across MON sites.The mean distributions at baseline varied across all sites and were not statistically significantly different (P>.05). Scores varied by domain across sites, although history and physical scores tended to be higher than work-up, diagnosis, and treatment scores. Pathway adherence also varied for specific diagnostic evaluations or treatments: surgery; sentinel/axillary lymph node dissection; radiation therapy; chemotherapy; and hormonal therapy, and also for the prevalence of unnecessary testing. CONCLUSION: Our study suggests that fostering the adoption of breast cancer clinical pathways into an oncology network is feasible; however, adherence to pathways in breast cancer is varied and reducing such variation is a priority as oncology networks continue to grow in popularity.

Rosai-Dorfman disease: tumor biology, clinical features, pathology, and treatment.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, nonmalignant clinical entity characterized by a group of clinical symptoms and characteristic pathological features. METHODS: Articles that reviewed tumor biology, clinical features, pathology, and treatment for RDD were identified in a search of the literature for the years 1990 to 2014. The results from this body of literature were reviewed and summarized. RESULTS: Patients with RDD generally present with massive, painless cervical lymphadenopathy, fevers, and elevated inflammatory markers. Extranodal disease is typical, with the most common sites being the skin and the central nervous system. Rarely, the gastrointestinal tract is involved. Immunohistochemistry remains the mainstay of diagnosis with S100 and CD68 positive cells while CD1a will be negative of involved histiocytes. Histologically, the disease shows the classical characteristic finding of emperipolesis. Many patients do not require treatment; however, surgical resection remains the mainstay of treatment for symptomatic disease. The role of steroids, chemotherapy, and radiation therapy continue to be based on small case series and case reports. CONCLUSIONS: RDD has a variable clinical presentation; therefore, a high degree of suspicion and a thorough pathological review are necessary to diagnose this rare clinical entity. Although some patients will experience spontaneous resolution, others may require surgical resection or steroid therapy and radiation or chemotherapy. Given the rarity of the disease and the lack of a clear therapeutic pathway, referring patients to a tertiary center is recommended for confirming the diagnosis and treatment considerations.

The thorny issue of relapsed acute myeloid leukemia.

PURPOSE OF REVIEW: Acute myeloid leukemia (AML) is a devastating disease, in which the majority of afflicted patients eventually experience relapse and die from their disease. RECENT FINDINGS: Clinical and molecular characterization of the disease have greatly aided in prognostication in both primary and relapsed settings, which may broadly guide therapy, but truly effective standards of care for relapsed AML remain lacking. Traditional chemotherapeutic drugs have modest but limited efficacy in relapsed AML, whereas more novel and potent cytotoxic chemotherapeutic agents hold promise and are entering the advanced phases of testing. Targeted therapies for AML have demonstrated activity, often as single agents, generating enthusiasm for further development in subgroups of patients with appropriate molecular anomalies. Finally, allogeneic stem cell transplantation continues to evolve as an effective and potentially curative therapy for limited numbers of patients with relapsed AML. SUMMARY: The complexity of relapsed AML will dictate the need for continued development of novel chemotherapeutic and targeted therapies that suit the molecular and clinical profiling of individual patients.

Measuring Advanced Practice Provider Productivity at the National Comprehensive Cancer Network's Member Institutions.

Introduction: The utilization of advanced practice providers (APPs) in oncology has been growing over the last decade; however, there is no standard method for assessing an APP's contributions to oncology care. Methods: The NCCN Best Practices Committee (BPC) created an APP Workgroup to develop recommendations to support the roles of APPs at NCCN Member Institutions. The Workgroup conducted surveys to understand how NCCN centers measure productivity. This article will review the survey results and provide recommendations for measuring APP productivity. Results: Although 54% of responding centers indicated they utilize relative value units (RVU) targets for independent APP visits, 88% of APPs are either unsure or do not believe RVUs are an effective measurement of overall productivity. Relative value units do not reflect non-billable hours, and APPs perform a significant number of non-billable tasks that are important to oncology practices. Sixty-six percent of APPs believe that measuring disease-based team productivity is a more reasonable assessment of APP productivity than measuring productivity at the individual level. Conclusion: Our recommendation for cancer centers is to focus on the value that APPs provide to overall care delivery. Advanced practice provider productivity metrics should consider not only the number of patients seen by APPs, but also the high quality and thorough care delivered that contributes to the overall care of the patient and practice. Advanced practice providers can help improve access to care, deliver improved outcomes, and increase patient and provider satisfaction. Reducing the focus on RVUs, accounting for important non-RVU-generating activities, and incorporating quality and team metrics will provide a better overall picture of APP productivity.

Budget Impact of Adaptive Abiraterone Therapy for Castration-Resistant Prostate Cancer.

BACKGROUND: The use of a novel strategy known as adaptive abiraterone therapy based on mathematical modeling of evolutionary dynamics of tumor subpopulations was shown in a clinical trial to extend the time to disease progression in patients with metastatic castration-resistant prostate cancer (CRPC) and reduced the use of abiraterone therapy. Although the clinical impact of adaptive abiraterone treatment is clear, the economic impact of this strategy has not been investigated. OBJECTIVE: To compare the cost of care with adaptive abiraterone therapy versus standard continuous abiraterone therapy in patients with metastatic CRPC, using patient billing data. METHODS: We performed a retrospective review of billing data for patients with metastatic CRPC who received abiraterone treatment at a large cancer center between June 1, 2012, and August 31, 2018. Patients were divided into 2 groups based on whether they received adaptive abiraterone therapy (N = 15) or continuous abiraterone therapy (N = 21). All patients with refractory, metastatic prostate cancer after castration that was indicated for abiraterone therapy were eligible for this study. Each patient in the adaptive abiraterone therapy cohort received abiraterone plus prednisone treatment until the patient reached a target threshold of 50% or more reduction in prostate-specific antigen (PSA) level compared with his PSA level before abiraterone therapy; treatment was then suspended until the PSA level rose above the 50% of PSA before abiraterone therapy target threshold. The continuous therapy cohort received abiraterone plus prednisone daily until radiographic progression. The primary outcomes were the mean annual cost of care per patient, including and excluding the cost of abiraterone, and the cost of care, by clinical category. RESULTS: The median time to disease progression was 25.8 months for patients who received adaptive abiraterone therapy compared with 12.1 months for patients who received continuous abiraterone therapy. Overall, the mean total, including the cost of drug, annual cost per patient who received adaptive abiraterone therapy was $79,093 compared with $146,782 for patients who received continuous abiraterone therapy (P <.0001). The annual cost of care per patient, excluding the cost of abiraterone, was $13,883 for those who received adaptive therapy versus $22,322 for those who received continuous abiraterone therapy (P = .2757), which was not statistically significant. CONCLUSION: Practical precision medicine strategies, such as adaptive abiraterone treatment or pharmacogenomics-targeted dosing, can use known biomarkers, such as PSA, to tailor therapy, generate improved outcomes, and reduce costs without the need for novel drug and diagnostic discovery and development. The results of this study suggest that a large clinical study of adaptive abiraterone therapy is warranted to validate the potential of this strategy to extend the time to disease progression and reduce costs of treatment of metastatic CRPC.

Prevalence of Preoperative Iron Deficiency Anemia: A Case Series Among Patients Undergoing Radical Cystectomy.

Anemia occurs in a significant group of patients with bladder cancer before radical cystectomy. Iron deficiency is a readily identifiable cause of anemia, which can be treated before surgery. The proportion of patients with bladder cancer with iron deficiency anemia is unknown. Laboratory and clinical outcomes were collected on 47 consecutive patients presenting for radical cystectomy. Iron studies found 30% of patients had iron deficiency anemia. These findings present an opportunity to treat anemia before surgery, to reduce blood transfusions during radical cystectomy.

Prospective CYP2C19-Guided Voriconazole Prophylaxis in Patients With Neutropenic Acute Myeloid Leukemia Reduces the Incidence of Subtherapeutic Antifungal Plasma Concentrations.

A risk mitigation strategy was implemented to determine if a higher prophylactic voriconazole dosage in patients with CYP2C19 rapid metabolizer neutropenic acute myeloid leukemia (AML) reduces the incidence of subtherapeutic trough concentrations. Patients with AML (n = 263) were preemptively genotyped for CYP2C19*2, *3, and *17 alleles as part of a single-center prospective, interventional, quality improvement study. CYP2C19 rapid metabolizers (CYP2C19*1/*17) were recommended to receive interventional voriconazole 300 mg twice daily, ultrarapid metabolizers (CYP2C19*17/*17) were recommended to avoid voriconazole, and all others received the standard prophylactic dosage of 200 mg twice daily. In this real-world setting, 202 patients (76.8%) were prescribed prophylactic voriconazole, and of these patients 176 (87.1%) received CYP2C19-guided prophylactic dosing. Voriconazole trough concentrations were obtained for 41 of the 58 (70.7%) CYP2C19 rapid metabolizers prescribed prophylactic voriconazole. Interventional voriconazole resulted in higher plasma trough concentrations (median 2.7 µg/mL) compared with the standard prophylactic dosage (median 0.6 µg/mL; P = 0.001). Subtherapeutic concentrations were avoided in 83.8% of CYP2C19 rapid metabolizers receiving interventional dosage compared to 46.2% receiving standard dosage (P = 0.02). CYP2C19 genotyping to preemptively guide prophylactic voriconazole dosing is feasible and may be a potential strategy for reducing the risk of subtherapeutic trough concentrations that potentiate breakthrough fungal infections.

A Better Pathway? Building Consensus and Engaging Providers with Feedback to Improve and Standardize Cancer Care.

INTRODUCTION: Unwanted clinical variation is common across the United States health care system and is particularly vexing in oncology owing to the complexity, morbidity, and high cost of the disease. Efforts to standardize care including guidelines and continuing medical education have had only limited impact. Disease-specific oncology clinical pathways hold the promise of reducing variation but have been hampered by a lack of ownership and accountability among oncology providers. MATERIALS AND METHODS: We describe the utility of combining a patient simulation-based clinical variation measurement with the in-house development of multidisciplinary breast cancer pathways at a National Cancer Institute-designated cancer center. RESULTS: At baseline, we found high variation in care decisions across the multidisciplinary team and within individual specialties in the management of simulated patients. Development and introduction of breast cancer clinical pathways combined with individual and group feedback on pathway adherence led to significant increases in pathway-aligned care decisions and decreases in measured variation. Overall quality scores increased from 47.5% to 61.1% (P < .001), with the largest improvement in diagnostic accuracy (+22.1%). Providers also ordered fewer unnecessary tests, saving an estimated $305 per patient case. Adherence to preferred chemotherapy regimens increased for both medical oncologists (+16%) and other members of the multidisciplinary team (+19%). CONCLUSION: Our work shows that a structured process to measure clinical variation and provide personalized feedback to an oncology multidisciplinary team drives adoption of evidence-based pathways, less unneeded spending, and higher quality care for patients.

National Comprehensive Cancer Network Infusion Efficiency Workgroup Study: Optimizing Patient Flow in Infusion Centers.

PURPOSE: The National Comprehensive Cancer Network (NCCN) formed an Infusion Efficiency Workgroup to determine best practices for operating efficient and effective infusion centers. METHODS: The Workgroup conducted three surveys that were distributed to NCCN member institutions regarding average patient wait time, chemotherapy premixing practices, infusion chair use, and premedication protocols. To assess chair use, the Workgroup identified and defined five components of chair time. RESULTS: The average patient wait time in infusion centers ranged from 25 to 102 minutes (n = 23; mean, 58 minutes). Five of 26 cancer centers (19%) routinely mix chemotherapy drugs before patient arrival for patients meeting specified criteria. Total planned chair time for subsequent doses of the same drug regimens for the same diseases varied greatly among centers, as follows: Administration of doxorubicin and cyclophosphamide ranged from 85 to 240 minutes (n = 22); of FOLFIRINOX (folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplation) ranged from 270 to 420 minutes (n = 22); of rituximab ranged from 120 to 350 minutes (n = 21); of paclitaxel plus carboplatin ranged from 255 to 380 minutes (n = 21); and of zoledronic acid ranged from 30 to 150 minutes (n = 22) for planned total chair time. Cancer centers were found to use different premedication regimens with varying administration routes that ranged in administration times from zero to 60 minutes. CONCLUSION: There is a high degree of variation among cancer centers in regard to planned chair time for the same chemotherapy regimens, providing opportunities for improved efficiency, increased revenue, and more standardization across centers. The NCCN Workgroup demonstrates potential revenue impact and provides recommendations for cancer centers to move toward more efficient and more standard practices.

Longitudinal cohort study to determine effectiveness of a novel simulated case and feedback system to improve clinical pathway adherence in breast, lung and GI cancers.

OBJECTIVES: This study examined whether a measurement and feedback system led to improvements in adherence to clinical pathways. DESIGN: The M-QURE (Moffitt-Quality, Understanding, Research and Evidence) Initiative was introduced in 2012 to enhance and improve adherence to pathways at Moffitt Cancer Center (MCC) in three broad clinical areas: breast, lung and gastrointestinal (GI) cancers. M-QURE used simulated patient vignettes based on MCC's Clinical Pathways to benchmark clinician adherence and monitor change over three rounds of implementation. SETTING: MCC, located in Tampa, Florida, a National Cancer Institute Comprehensive Cancer Center. PARTICIPANTS: Three non-overlapping cohorts at MCC (one each in breast, lung and GI) totalling 48 providers participated in this study, with each member of the multidisciplinary team (composed of medical oncologists, radiation oncologists, surgeons and advanced practice providers) invited to participate. INTERVENTIONS: Each participant was asked to complete a set of simulated patient vignettes over three rounds within their own cancer specialty. Participants were required to complete all assigned vignettes over each of the three rounds, or they would be excluded from this study. PRIMARY OUTCOME MEASURE: Increased domain and overall provider care adherence to clinical pathways, as scored by blinded physician abstractors. RESULTS: We found significant improvements in pathway adherence between the third and first rounds of data collection particularly for workup and treatment of cancer cases. By clinical grouping, breast improved by 13.6% (p<0.001), and lung improved by 12.1% (p<0.001) over baseline, whereas GI showed a decrease of 1.4% (p=0.68). CONCLUSIONS: Clinical pathway adherence improved in a short timeframe for breast and lung cancers using group-level measurement and individual feedback. This suggests that a measurement and feedback programme may be a useful tool to improve clinical pathway adherence.

Recurrent excitation in the dentate gyrus of a murine model of temporal lobe epilepsy.

Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.