bluuebunny/crossref_metadata_2025 huggingface dataset:
Creating and developing games throughout interdisciplinarity and patient participation.
Authors: Mozzilli Simone Lehwess , Sassi Elisa , Rossi Ludmilla , Sonaglio Viviane , Francisco Fernanda , Duarte Adriana , dos Santos Lisandra Panzoldo , Yabu Gica , Sredni Simone Treiger
Published: September 2018

e18231

Background: In an increasingly technological world, digital information about childhood cancer that is easily accessible to pediatric patients, their families and healthcare providers is still missing.  In this scenario, we decided to bring all our stakeholders – patients, caregivers, healthcare professionals, creatives and entrepreneurs - together to create an application for tablet and mobile devices that would help children demystify cancer and its treatment. Methods: Materials and platforms used included:  1- Interdisciplinarity: which involves the combination of two or more academic disciplines into one activity; 2- Design Thinking: a human-centered methodology for a rapid ideation (idea generation) with the ability to visualize and adapt the results in near real-time;  3- Agile UX: a methodology which integrates the user experience design team and the developer team;  4- Patient Centered Design;  5- Project Management Platforms; 6- Collaboration and Communication Tools. Results: 1- Development of an application with 20 minigames for iOS and Android platforms, in a language that is easily accessible to children with an attractive an colorful interface where the child can identify him/herself with a custom designed character that guides them through different steps of the treatment. The initiative was highlighted in the AppStore and resulted in almost 4 million views. 2- Acquisition and expansion of interdisciplinarity for all stakeholders.  3- And most importantly, development of empathy and compassion for our patients. Conclusions: The interdisciplinarity and the effective participation of all the stakeholders in the project, allowed an integrated access to information, facilitating the understanding, identification, codification and availability of information that resulted in generation of easily accessible knowledge to our targeted population.  The greatest transformation was not only in the technological advance itself, but in our new way to associate knowledge with human factors in order to educate, empower and improve the quality of life of children fighting cancer. www.beaba.org/games The app is currently available only in Portuguese, but we are raising funding to translate to other languages.
Characteristics of breakthrough therapy designation requests (BTDRs) submitted to the Office of Hematology and Oncology Products (OHOP), FDA.
Authors: Suzman Daniel L. , Kluetz Paul Gustav , McKee Amy E. , Ward Ashley Flynn , Marcus Leigh Jessica , Casak Sandra J. , Pazdur Richard
Published: September 2018

e18236

Background: Breakthrough therapy designation is an FDA program intended to expedite the development of drugs and biologics that provide preliminary clinical evidence of a substantial improvement over existing therapies. The factors needed to demonstrate this improvement in oncologic therapies have not been well-described. Methods: We reviewed the characteristics of BTDRs submitted to OHOP from program initiation to the present. Results: From November 2013 through July 2016, there were 134 BTDRs for 96 drugs submitted to OHOP, not including 14 BTDRs intended for benign hematologic or supportive care indications. The most common drug mechanisms of action (MoA) were tyrosine kinase inhibitor (TKI) (37; 28%), immunotherapy (24; 18%), and targeted antibodies (21; 16%). Of the 134 BTDRs, 56 (42%) were granted. BTDRs were granted most frequently for TKIs (22; 59%) and immunotherapy (14; 58%) and were rarely granted for cytotoxic (1; 10%) or endocrine (0) therapies. BTDRs based on randomized trials were more frequently granted than those based on single-arm trials (49% vs 39%), as were BTDRs based on OS versus ORR or PFS (57% vs 41%). In BTDRs based on single-arm trials, the median number of patients was higher in those granted versus denied or withdrawn (41 vs 26 patients). Among BTDRs granted based on ORR in solid tumors, the ORR ranged from 24% to 94%, reflecting variation in available therapies, MoA, toxicity, and durability of response. Conclusions: The likelihood of a successful BTDR increases with randomized trial design and larger sample size. Additional considerations include MoA, duration of ORR, and choice of endpoint. [Table: see text]
RAS mutation testing and cetuximab use for colorectal cancer at VA Hospitals.
Authors: Lee Steve Young , Becker Daniel Jacob , DuVall Scott , Lynch Julie Ann
Published: September 2018

e18244

Background: Extended RAS testing in colorectal cancer predicts response to therapy with EGFR-directed therapies cetuximab and panitumumab. In 2010 VA policy recommended testing of all potentially treatable metastatic colon cancer patients for KRAS mutations. We explored the uptake of RAS testing within the VA system and characterized mutation frequency and cetuximab use. Methods: We extracted records of VA patients with first primary colorectal cancers diagnosed between 2011 and 2015 from the VA Central Cancer Registry (VACCR). We included patients who had RAS testing from 4 commercial laboratories contracted with the VA . We gathered genomic testing results from the commercial vendors. We calculated descriptive statistics of mutation sites and used multivariable logistic regression to evaluate predictors of mutations and cetuximab use. Results: Colon cancer diagnoses decreased in the VA from 4285 cases in 2011 to 3275 cases in 2015 and we observed a concurrent increase in KRAS testing from 4.7% in 2011 (202 cases) to 10.3% in 2015 (336 cases) (p < 0.001). KRAS tested patients were 65.7% white, 26.1% black, 3.1% Hispanic, and 2.8% female. Among 1717 patients tested, 588 had mutations (34.2%), with 441(75%) in codon 2, 117 (19.9%) in codon 13, 23 (3.9%) in codon 61. There were no differences in mutation rates by age, race, ethnicity, or gender categories. A total of 189 patients received cetuximab; 11 of 558 (1.9%) KRAS mutants and 178 of 1095 (16.2%) KRAS wildtype received cetuximab. Across all patients, increasing age in years predicts for cetuximab non-use (OR 0.983, 95% CI 0.97-0.99); gender, race, and ethnicity did not. Conclusions: We found a significant increase in KRAS testing between 2011 and 2015, with mutation patterns reflective of the US population. We found a low rate of inappropriate cetuximab use among patients with KRAS mutations, as well as an also low rate of cetuximab use among KRAS wild type patients among which it may be indicated. Further study is warranted to understand patterns of appropriate and inappropriate use of targeted agents.
Health care associated infections (HAIs) a growing challenge in low-middle-income countries: A Brazilian prospective cohort study.
Authors: Costa Jose Iran , Mello Maria Julia Gonçalves , Barros Isabella R . da Cunha , Ramos Camila jacó , Neves Naiá de miranda , Telles O Lima Jurema
Published: September 2018

e18253

Background: Healthcare associated infections (HAIs) are responsible for morbidity and mortality among oncologic patients. The aim of this study was to determine the risk factors and the profile of HAI in patients admitted in cancer center. Methods: a prospective cohort study approved by the institution’s ethics committee.It was completed standardized initial assessment and conducted telephone follow-up after thirty days and sixty days from hospital discharge records and supplemented with analysis and hospital information system.Data were analyzed using Cox proportional hazards models. Results: 220 patients between 20 and 87 years of IMIP Adult Oncology service, from December 2015 to June 2016. Among the 220 cancer patients included in the study, the prevalence of HAI was 73.6% and the mortality was 40.4%. 90% percent of patients were initially treated at emergency service. Elderly patients had a higher risk of developing HAI(p < 0.001) as well as people who had longer period of hospitalization(p < 0.001), advanced cancer, people who reported fever on admission, who were diagnosed with Febrile neutropenia(p < 0.001) .The most frequent infections were urinary tract infection, followed by pneumonia and bloodstream infections, which are caused most commonly by Gram-negative microorganisms, and Klebsiella pneumoniae ESBL the most common.Conclusions: HAI is a prevalent problem in the whole course of cancer care with significant morbidity and mortality. Health professionals, especially in the emergency department, must be able to identify and appropriately treat HAI. Bacterial multidrug resistance was prevalent, and may be in the future because of great loss of scientific advances made in the oncology area to date. Institutional policies for prevention, surveillance and HAI therapy must be priority in cancer population.
Safety and efficacy of direct oral anticoagulants (DOAC) in cancer patients: Meta-analysis of randomized controlled trials (RCT).
Authors: McBride Ali , Katragadda Chinmayee , Abraham Ivo
Published: September 2018

e18264

Background: The DOACs apixaban, edoxaban, rivaroxaban, dabigatran offer advantageous alternatives for venous thromboembolism (VTE) treatment in cancer patients, however, there lacks a prospective assessment in this population. We conducted a meta-analysis of RCTs comparing these DOACs to controls to evaluate the safety and efficacy of these new agents for patients with active cancer. Methods: We systematically searched PUBMED, EMBASE, Cochrane Reviews, CINAHL and Clinicaltrials.gov. Two authors (CK, IA) screened and reviewed abstracts and full text, with disagreements resolved by third author (AB). Data extracted included major bleeding and clinically relevant nonmajor bleeding for safety; recurrent VTE and VTE death for efficacy. Analyses included Mantel-Haenszel random effects risk ratios (RR); I2 for heterogeneity; and meta-regression by publication year. Results: Of 2307 records reviewed, 8 RCTs were retained. Pooled analysis yielded safety RR 0.82 (95%CI = 0.56-1.21, I2 = 44% ) and efficacy RR 0.94 (95%CI = 0.68-1.31; I2 = 0%). Meta-regression revealed no publication year bias. Conclusions: Current guidelines have not supported the use of DOACs in clinical cancer practice due to the paucity of data in this setting. Our results indicate no differential efficacy and no increased bleeding risk for DOACs in cancer patients. Additional prospective research is required to determine long term effects in subgroups of cancer patientss at higher risk for VTE or bleeding events. [Table: see text]
Potentially avoidable hospitalizations in patients with advanced cancer.
Authors: Johnson Connor , Xiao Yian , El-Jawahri Areej , Wong Risa , D'Arpino Sara , Moran Samantha M.C. , Lage Daniel E , Temel Brandon , Ruddy Margaret , Pirl William F. , Traeger Lara , Lennes Inga Tolin , Cashavelly Barbara J. , Martinson Holly S , Jackson Vicki , Greer Joseph A. , Ryan David P. , Hochberg Ephraim P. , Temel Jennifer S. , Nipp Ryan David
Published: September 2018

e18275

Background: Cancer patients and their clinicians often wish to avoid preventable hospital admissions, but efforts to understand the predictors of avoidable hospitalizations are lacking. We sought to examine reasons for hospital admissions in patients with advanced cancer, identify potentially avoidable hospitalizations (PAH), and explore predictors of PAH. Methods: We prospectively enrolled hospitalized patients with advanced cancer from 9/2014 - 11/2014 as part of a longitudinal data repository to define symptom burden in this population. Upon admission, we assessed patients’ symptom burden (Edmonton Symptom Assessment System [ESAS]; scored 0-10). We created a summated ESAS physical symptom variable. We used consensus-driven medical record review to identify the primary reason for each hospital admission and categorize it as PAH or not based on of an adaptation of Graham’s criteria for PAH. We used mixed multivariable logistic regression analyses to identify predictors of PAH. Results: We assessed 477 hospital admissions in 200 consecutively admitted patients (mean age = 64.6; 47% female; 67% married). Over half of admissions came through the emergency department (56%). The most common reasons for admissions were fever/infection (30%), symptoms (26%), and planned admission for chemotherapy or procedure (10%). We identified 149 (31%) as PAH. Among these PAH, 45 (30%) were readmissions due to failure of timely outpatient follow-up (within 7 days of discharge) and 44 (30%) were due to premature discharge from prior hospitalization. In a mixed logistic regression model, being married (odds ratio [OR] 0.48 [0.28-0.81]; p < 0.01) was associated with lower likelihood of PAH, while higher physical symptom burden (OR 1.02 [1.00-1.04]; p = 0.04) was associated with greater likelihood of PAH. Conclusions: We identified that a substantial proportion of hospitalizations in patients with advanced cancer are potentially avoidable, often related to failure of timely outpatient follow-up and premature hospital discharge. Our results demonstrate that patients’ symptom burden predicts PAH, thus underscoring the need to address patients’ symptoms in order to reduce preventable hospital admissions.
Risk of gastrointestinal and hepatic toxicities in patients with hormone receptor-positive HER2-negative breast cancer treated with CDK 4/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials.
Authors: Tun Aung , Thein Kyaw Zin , Thar Yu Yu , Nayak Asha , Guevara Elizabeth
Published: September 2018

e18284

Background: CDK4/6 inhibitors are proven to be beneficial in patients with hormone receptor-positive HER2-negative breast cancer. Studies have suggested an increased risk of gastrointestinal (GI) events. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the risk of GI and hepatic toxicities. Methods: We systematically conducted a comprehensive literature search using MEDLINE and EMBASE databases through January 1, 2017. RCTs that mention GI symptoms and/or elevation of liver enzymes as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Results: Five RCTs with a total of 2021 patients were eligible for analysis. The study arm used palbociclib-letrozole, palbociclib-fulvestrant, and ribociclib-letrozole while the control arm used placebo with letrozole or fulvestrant. The relative risks of all-grade elevated AST was 2.6 (95% CI: 1.15–5.86; p = 0.02); all-grade elevated ALT: 2.82 (95% CI: 1.25–6.36; p = 0.01); all-grade stomatitis: 3.32 (95% CI: 2.09-5.28; p < 0000.1); all-grade nausea: 1.79 (95%CI: 1.25-2.58; p = 0.002); all-grade vomiting:1.55 (95% CI: 0.92-2.63; p = 0.10); and all-grade diarrhea: 1.59 (95% CI 1.28-1.98; p < 0.0001). The relative risks of high-grade elevated AST was 3.08 (95% CI: 1.42–6.67; p = 0.004); high-grade elevated ALT: 7.2 (95% CI: 2.81–18.43; p < 0.0001); high-grade stomatitis: 2.01 (95% CI: 0.22-18.02; p = 0.53); high-grade nausea: 0.76 (95%CI: 0.12-4.78; p = 0.77); high-grade vomiting: 0.88 (95% CI: 0.19-4.13; p = 0.87); and high-grade diarrhea: 1.23 (95% CI 0.52-2.92; p = 0.64). Conclusions: Our meta-analysis demonstrated that CDK 4/6 inhibitor-based regimens are associated with a higher risk of all-grade and high-grade elevated AST and ALT. Moreover, the regimen is associated with increased risk of all-grade stomatitis, nausea and diarrhea. Recognizing these adverse effects may help clinicians in delivering proper supportive care and thereby enhancing patients’ quality of life.
Comparison of incidence and average cost per toxicity in patients treated with nivolumab and pembrolizumab.
Authors: Mason Neil Thomas , Antonia Scott Joseph , Khushalani Nikhil I. , McLeod Howard L.
Published: September 2018

e18292

Background: PD-1 inhibitors such as nivolumab and pembrolizumab have demonstrated efficacy in numerous metastatic cancers. However, these drugs are also some of the most expensive and can have severe adverse side effects. However, most available data comes from clinical trials rather than patients treated in clinical practice as standard-of-care. This study reports the incidence of severe toxicities in a number of cancer types and estimates the per patient cost of managing these toxicities. Methods: All patients treated with nivolumab or pembrolizumab between January 1, 2014 through April 30, 2016 were identified at Moffitt Cancer Center (nivolumab N=74, pembrolizumab N=134). Toxicities occurring during or within 2 months of stopping treatment were identified and graded using the CTCAE 4.0 criteria. A cost of care analysis was performed comparing patients with Grade 3-5 toxicities to patients with Grade 0-2 toxicities. Results: The most common severe toxicities were anemia, dyspnea, dermatitis, hepatitis, and renal failure (Table 1). The average cost of care for patients experiencing Grade 3-5 toxicities was $640 and $4,784 higher than those without toxicity in nivolumab and pembrolizumab, respectively. Conclusions: Primary cost drivers differed between the two drugs with outpatient visits and additional pharmacy costs driving nivolumab cost while inpatient stays and radiation therapy drove costs with pembrolizumab. The large difference between the toxicity cost of each group could be due to the heterogeneity of cancer types treated with nivolumab versus primarily melanoma in the case of pembrolizumab or the smaller sample size of nivolumab patients. [Table: see text]
Value of life and time: A survivorship perspective.
Authors: Hinkel Jennifer M. , Sexton Daniel B. , Egan-Kunicki Justine
Published: September 2018

e18298

Background: Common tools to quantify value of life years after a cancer diagnosis include the Quality Adjusted Life Year (QALY). This measure is partly based on health utility states derived from Quality of Life (QoL) survey instruments such as the EQ-5D. Research has identified shortcomings in applying the QALY, including the potential for underestimating value. QoL surveys may fail to capture the full range of potential health states, or the values derived may fail to reflect patient perspectives of value. Methods: An online survey was piloted with a convenience sample of cancer survivors via two US survivor Facebook groups over two weeks in Jan. 2017 to explore these themes. Results: 116 complete responses were analyzed (of 123 respondents). Original diagnoses included solid tumors and hematologic malignancies, and respondents were between one and 32 years post-diagnosis (PoD). Most (101, 87%) had completed active treatment. A majority (85, 73%) rated PoD years as having more value than years pre-diagnosis (PreD). 83% (98) indicated that they felt their time is more valuable since their diagnosis. While the majority of respondents (57%) assigned a lower value to the 12 months immediately following diagnosis compared to the value of a PreD year, a majority (55%) also valued the most recent twelve months to have equal or greater value than a PreD year. Many assigned higher valuations to PoD years even when simultaneously reporting limitations in Activities of Daily Living (ADLs). Conclusions: Comparing survivor valuations of PoD life years to valuations derived by utility state instruments has not been heavily researched. This survey generates additional hypotheses. First, assuming PoD years hold lower value than PreD years may underestimate value compared to a survivor’s view. Second, QoL instruments may not be capturing positive changes in PoD years, some of which have been documented in psychology research, such as Post-Traumatic Growth or increased feeling of meaningfulness. Further investigation is imperative to ensure that value determinations have a solid evidentiary basis and reflect patient-centered viewpoints, particularly as the “value debate” influences patient access to care.
The impact of pricing strategy on the cost of oral anti-cancer drugs during dose reductions.
Authors: Truong Judy , Chan Kelvin K. , Mai Helen , Chambers Alexandra , Sabharwal Mona , Trudeau Maureen E. , Cheung Matthew C.
Published: September 2018

e18312

Background: The pricing strategy of oral medications can affect their costs. The strategy of flat pricing per tablet may increase drug costs in the event of dose reductions requiring more tablets, as there is a single price for different tablet strengths, but the impact is largely unknown. With the strategy of linear pricing, the tablet price increases with its strength. We sought to determine the impact of pricing strategy on the cost of oral anti-cancer drugs during dose reductions. Methods: Oral anti-cancer drugs reviewed by the pan-Canadian Oncology Drug Review were identified between July 2011 to January 2015. The pricing strategy of these drugs was reviewed. We examined the percentage change in cost per mg and cost per 28 days as a result of dose reduction from dose level 0 to -1 and -2 for each drug. Results: Seventeen drugs for use in 20 indications were included in the analysis. There were 3 drugs for hematological malignancies and 14 drugs for solid cancers. Fifty-nine percent (10/17) of these drugs were available in multiple strengths; five of them utilized fixed pricing per tablet strategy and the other 5 utilized linear pricing. The remaining drugs (7/17) were available in a single strength tablet. Dose reductions generally increased the cost per mg for drugs using flat pricing per tablet, with a mean increase of 82% (range: 25%-200%) at dose level -1 and 100% (range: 0%-200%) at dose level -2. Dose reduction had no effect on the cost per mg of drug for drugs using linear pricing apart from lenalidomide, which had increased costs due to minimal price variation between the highest and lowest tablet strengths. In general, dose reduction did not decrease the cost per 28 days of drug for drugs using flat pricing per tablet, but was proportionally reduced in drugs using linear pricing. Conclusions: While there is a general expectation that the cost of drugs should decrease with dose reduction, oral anti-cancer drugs using flat pricing per tablet have increased cost per mg and no decrease in cost per 28 days despite dose reduction. Future economic evaluations should account for the impact of dose reductions for oral drugs using the flat pricing per tablet strategy on cost-effectiveness and budget.
Cost-effectiveness of genotype-guided aspirin use for colorectal cancer prevention.
Authors: Biltaji Eman , Au Trang H. , Walker Brandon , Ose Jennifer , Ulrich Cornelia M , Stenehjem David D. , Brixner Diana I.
Published: September 2018

e18318

Background: Colonoscopy is the “gold standard” for colorectal cancer (CRC) screening. However, adherence rates are low and detection is not optimal. Concomitant aspirin chemoprevention is recommended by US Preventive Task Force, but bleeding complications can be limiting. Variant genotypes in aspirin metabolism can modify CRC and adenoma risk. Genotype guided aspirin (ggASA) use will identify a targeted average-risk population for maximal aspirin benefit while minimizing adverse events rates compared to the general population. We conducted a cost-effectiveness analysis (CEA) of primary chemoprevention in CRC using ggASA compared to no intervention, and colonoscopy ±general aspirin in healthy average-risk individuals. Methods: Our Markov decision analytical model consisted of 5 possible health states: no CRC/polyps, adenoma, pre-clinical CRC, CRC, and death. Model probabilities for CRC and its prevalence were estimated using SEER database and published literature. A microsimulation of 10,000 individuals aged 50-64 years was used to estimate cost-effectiveness from US payer perspective over lifetime. One way and probabilistic sensitivity analyses and model validation results will be reported in the final poster. Results: Our results suggest that compared to colonoscopy and no intervention, ggASA was associated with fewer CRC cases, and CRC-related deaths and MI cases. Compared to colonoscopy + general aspirin, ggASA was associated with fewer bleeding events, similar rates of CRC and CRC-related deaths, and fewer MI cases prevented. From a cost-effectiveness standpoint, ggASA use over a lifetime had the lowest costs and highest quality adjusted life years gained compared to other strategies, if testing costs were ignored. Once genetic testing costs exceeds $63, colonoscopy + general aspirin becomes the most cost effective strategy. Between genetic testing cost of $63-283, the costs of using ggASA per quality adjusted life year gained is below $100,000. Conclusions: Genotype-guided aspirin use precisely identifies an average-risk population, and lowers adverse events rates compared to general aspirin. The economic value of genotype-guided aspirin is dependent on the genetic testing costs.
Financial toxicity of cancer treatment at a large academic cancer center.
Authors: Ahuja Parikh Divya , Amin Krunal , Hall Evan Thomas , Patel Manali I.
Published: September 2018

e18323

Background: Many studies have shown that patients with cancer are at higher risk of financial difficulty than those without cancer. Given the rising cost of cancer therapy it is important to study the financial distress associated with cancer care. Therefore, we assessed patient reported financial toxicity at a large tertiary academic cancer institute. Methods: From July 2014 to August 2014, we asked 300 patients at the Stanford Cancer Center to participate in an 11-item questionnaire about costs incurred with cancer care. We calculated patient-reported financial toxicity using the COST score, validated at the University of Chicago (scores range from 0-44 with higher values indicating higher financial burden). We obtained demographic information including sex (male or female), education level (high school or less, associates/bachelors degree, or masters/professional degree), race (white or non-white) and annual household income ( < $49,999, $50,000-$99,999, or > $100,000) and used multivariable logistic regression to analyze the association between demographic factors and COST score. Results: Out of the 300 patients approached 254 patients (84.7%) participated in the survey. Nearly half (46%) responded that they “worry about the financial problems in the future as a result of illness or treatment“ quite a bit (4) or very much (5). More than half (52%) reported “I feel I have no choice about the amount of money I spend on care” quite a bit (4) or very much (5). Of patients without missing data (n = 184, 61.3%), the mean COST score was 21 (range 2-41). There were no significant differences in COST score by sex, education level, or race. However, there was a significant difference in COST score by annual household income with a higher degree of financial burden in the lowest income group (OR = 1.04, CI = 0.69-1.38, p < 0.001). Conclusions: Financial toxicity is an unmet concern among patients in our single institution study, with increased burden expressed by those in lower income groups. Our results demonstrate that financial toxicity is a critical concern despite our limited sample. Multicenter studies should be conducted to better characterize the risk factors and serve as a basis for interventions for patients at risk for financial toxicity.
Cost effectiveness in a supportive care unit.
Authors: Morin Sophie , Leroy Pauline , Aubaret Christophe , Legeay Karine , Saadi Alexandre , Brami Cloé , Gervais Claire , Herve Christian , Mamzer Marie-France , Sauvajot Clarisse , Guillou Anne , Garnier Barbara , Lecuru Fabrice , Waechter Lorraine , Scotte Florian
Published: September 2018

e18326

Background: Supportive care in cancer (SCC) may create a financial burden, compared to a standard cancer department. In 2011, a specific SCC inpatient unit was developed in an academic hospital, based on a multidisciplinary approach in order to anticipate patient’s disability and limit emergency hospitalization. Assess the cost effectiveness of the SCC unit expenses and benefits compared to Medical (MO) and Gastro-Intestinal (GI) oncology departments. Methods: Data were analyzed over a six year period (2011-2016). Cost of hospital stays and cost per year were calculated based on the hospital’s standard cost accounting method. Hospital benefits were calculated as the difference between total incomes and total expenses (cost and Diagnosis Related Group tariffs for the stay) and results were compared (period available for comparison 2011 to 2014). Results: Total costs for the hospital, primarily due to staff expenses, were lower for the SCC unit compared to MO and GI in 2011 and 2014, as well as the daily cost per stay (DCS). Benefit per year was also higher for the SCC unit permitting it, to benefit financially compared to the two other oncology units (Table). Incomes reimbursed by the National Health system for SCC unit were 1,632,601 euros in 2015 and 2,096,285 euros in 2016 with a total of 357 and 408 patients admitted in the 8 bed SCC unit in 2015 and 2016 respectively. Conclusions: The SCC unit was less expensive to operate compared to our other oncology units. Our results suggest that its development permitted the oncology department to enhance its quality of care without any additional expenses. [Table: see text]
Cancer antigen 125 (CA125) and the law of unintended consequences.
Authors: Alken Scheryll Paula , Coate Linda E. , Woulfe Bernie , O'Leary NIamh , Capin Ivana M , Blake Ophelia , Gupta Rajnish K.
Published: September 2018

e18327

Background: CA125 is a serum tumour marker used to monitor patients with ovarian cancer (OvCa). Its usefulness as a screening tool remains unproven. There is no restriction in its use at our institution, a university teaching hospital. We sought to establish patterns of testing during one calendar year (2013), focussing on the economic costs of such unrestricted testing. Methods: A lookback of the CA125 reports issued by the Biochemistry Laboratory was undertaken. The CA125 requests were from physicians within the hospital & from the community. Individual requests for CA125 & those part of tumour marker panel were included & correlated with radiology & histopathology records to identify subsequent investigations (invxs) & diagnoses (dxs). Economic costings were provided by hospital finance department. For the purpose of this study we only included the costs of invxs triggered by out of range CA 125 test results. Results: In 2013, 7,132 CA125 measurements were performed. 871 repeat tests, 40 tests performed on men & 16 tests with inadequate patient identifiers were excluded. Of the remaining 6,205 patient tests; median age was 53yrs (range 13 – 96yrs); median CA125 was 5.5 IU/L (range 0.1 – 22452 IU/L). Out of range tests (>35 IU/L) led to 619 ultrasound scans, 339 CT scans. In total, 20 new cases of OvCa were dx. The crude cost per new dx was €11,459.80. Median time to diagnosis was 4 days (range -2 – 251), median CA125 at dx was 271 (range 8.1 - 9444). Median age at dx was 62 (range 40 – 87). 65% of dx were made during inpatient stays;10% by family physicians;25% by gynaecologists. There was a statistically significant difference in median CA125 in patients diagnosed with OvCa, compared to those who were not dx with a malignant condition (p<0.0001); this was not true of age at dx (p=0.27). Conclusions: This study underlines the lack of efficacy in unrestricted serum CA125 testing & that such testing creates a significant economic burden on hospitals, far in excess of the cost of the CA125 test alone. We plan to implement guidelines in our institution & will reassess this issue following an education programme with local clinicians. [Table: see text]
Burden of acute myeloid leukemia (AML) in a U.S. commercially insured population.
Authors: Hagiwara May , Sharma Arati , Chung Karen C , Delea Thomas E.
Published: September 2018

e18330

Background: AML accounts for 25% of acute leukemias in adults worldwide, with an estimated 5-year survival of 26% in the US. Up-to-date information on the clinical and economic burden of AML among US commercially insured patients (pts) is needed to inform reimbursement decisions. Methods: This retrospective study of the burden of AML in a US commercially insured population used the IMS PharMetrics Plus health insurance claims database. Adults with ≥1 claim with a diagnosis (Dx) of AML (ICD-9-CM 205.00, 205.01, or 205.02 or ICD-10-CM C92.00, C92.40, C92.50, C92.01, C92.41, C92.51, C92.02, C92.42, C92.52) during the study period (Jan 2008 through Dec 2015) were identified. To avoid rule-out diagnoses, pts with only 1 outpatient claim (or >1 claim on a single day) with a Dx of AML not in relapse or remission were excluded. Annual incidence and total and AML-related inpatient and outpatient healthcare costs per person year (PY) were calculated by age and gender. For cost analyses, pts with newly diagnosed AML were assessed. To ensure adequate claims history to identify all prevalent cases, prevalence was calculated for the last year of the study period. Results: 26,344 adults with AML were identified during the study period, which covered 228.3 million PY of enrollment. The incidence rate was 4.9 per 100,000 PY. Incidence was greatest in men and pts aged 60+ years. Prevalence was 12.2 per 100,000 persons. Among 11,170 newly diagnosed AML pts, total average costs were $352,138 per PY. 63% of costs were for AML-related care. 70% of AML-related costs were for inpatient care. Costs were greatest for men, pts aged 45-59 years, and during the first 6 months post-diagnosis. Conclusions: Although AML is relatively rare, its economic burden to US commercial insurers is substantial. [Table: see text]
Clostridium difficile infection in acute myeloid leukemia patients.
Authors: Bal Anjali , Morris Amy , Naeem Mohammed Athar , Thomas Tanya , Keng Michael Kenneth
Published: September 2018

e18503

Background: Clostridium difficile infection (CDI) is the most important cause of nosocomial infectious diarrhea. Studies suggest patients (pts) undergoing acute myeloid leukemia (AML) chemotherapy (ctx) are at high risk of contracting CDI, but clinical and disease characteristics are not described. This study reports CDI rates and disease characteristics in AML pts at University of Virginia (UVA). Methods: A retrospective review of consecutive pt-encounters undergoing AML ctx at UVA from 2011-2016 was conducted. The main endpoint was to determine the rate of CDI within 90 days of ctx initiation, while assessing pt characteristics, comorbidities, risk factors, and disease specific indices associated with CDI. Statistical methods include nonparametric Wilcoxon and Fisher’s exact tests, with significance defined as p-value < 0.05. Results: Of 142 pts, 44 (31%) AML pts had CDI. 7 pts (15.9%) had 1 recurrent CDI episode,;2 pts (4.5%) had more than one. 18 pts (40.9%) underwent CT imaging specifically for CDI, revealing 3 pts (6.8%) with typhilitis and 2 pts (4.5%) with toxic megacolon requiring colectomy. There was no CDI associated mortality. At CDI diagnosis, 33 pts (75%) were neutropenic and 14 pts (31.8%) received prophylactic antibiotics. Median time from ctx was 12 days. Treatment for CDI: 38 pts (86.4%) single agent metronidazole or vancomycin and 6 pts (13.6%) combination. Sixteen (36.3%) CDI pts achieved CR, while 18 (40.9%) pts relapsed from AML. Compared to non-CDI pts, CDI pts were younger (50 v 59), less obese (BMI 26 v 29), poor-risk cytogenetics (26.5% v 14.1%), CKD (6.8% v 0.7%), prior cancer (6.8% v 2.8%). No statistical difference was seen in demographics (gender, race), comorbidities (tobacco use, pulmonary and cardiac disorders), or AML characteristics (bone marrow cellularity and blast, length of stay). Conclusions: The study concludes that the incidence of CDI in AML pts undergoing ctx is greater than hospitalized patients with or without malignancy as reported in the literature. CDI incidence is increased in younger, less obese, history of CKD or cancer, and poor-risk cytogenetics, suggesting potential predictive risk factors for CDI in AML pts. Further prospective studies are needed to confirm these potential CDI risk factors.
Quality-adjusted life years (QALY) for inotuzumab ozogamicin vs standard of care for relapsed/refractory acute lymphoblastic leukemia (R/R ALL).
Authors: van Oostrum Ilse , Su Yun , Heeg Bart , Wilke Thomas , Smith Alexander , Loberiza Fausto Rodriguez
Published: September 2018

e18506

Background: Inotuzumab Ozogamicin (InO), an anti-CD22 antibody-calicheamicin conjugate, has demonstrated superior clinical activity versus standard of care (SOC; intensive chemotherapy), including clinically meaningful improvement in overall survival (OS), high rates of complete remission (CR) and stem cell transplantation (SCT), and favorable patient-reported outcomes for R/R ALL in the phase 3 INO-VATE trial. Quality of life is an important consideration for R/R ALL patients in both short- and long-term survival. This study aimed to estimate mean overall survival adjusted for QoL (QALY) for patients treated with InO v SOC. Methods: A Markov model was developed with five health states - No CR, CR, post-SCT, progression, and death. Transition probabilities between health states and mortality rates were based on the InO-VATE trial. These rates were extrapolated to a lifetime horizon using parametric survival curves fitted to available OS data, and published literature for survival after SCT. Utilities (QoL valuations) for each health state were based on the patient-reported EQ-5D scores collected in the InO-VATE trial and a literature review. Adverse events experienced during and after treatments, including as a result of subsequent SCT, were taken into account in overall QoL. Outcomes were discounted at 1.5% and half-cycle corrected. Results: The estimated mean LY and QALY in each health state for InO and SOC and their differences are shown in Table. Most gains in LY and QALY for InO over SOC were from Post-SCT. Conclusions: This analysis taking into account both quantity and quality of life estimates InO offers an average of nearly 2 more years of QALY compared to SOC in R/R ALL, based on higher CR and SCT rates and better QOL. This is mainly driven by long-term gains of SCT. This can help inform patients, physicians and payers in decision making. [Table: see text]
Effect of echocardiogram prior to induction therapy for acute myeloid leukemia on detection of cardiac dysfunction and treatment modifications.
Authors: Yui Jennifer C. , Mudireddy Mythri , Patnaik Mrinal , Gangat Naseema , Al-Kali Aref , Elliott Michelle A. , Hogan William J. , Hook Carl C. , Wolanskyj Alexandra P. , Pardanani Animesh Dev , Villarraga Hector R. , Litzow Mark Robert , Tefferi Ayalew , Begna Kebede
Published: September 2018

e18514

Background: Standard induction therapy for acute myeloid leukemia (AML) includes “cytarabine and anthracycline”. Anthracyclines are known to cause acute, subacute and chronic cardiac complications ( Lefrak , EA et al, Cancer 1973:32(2):302-314; Singal, PK et al, NEJM 1998;339(13):900-905). It is recommended to do base line cardiac function assessment with echocardiogram prior to induction therapy containing anthracycline. This study was done to find the frequency of changes made in avoiding anthracycline usage following this evaluation. Methods: The Mayo clinic data base was interrogated to identify patients with newly diagnosed AML who underwent echocardiogram prior to anthracycline containing induction chemotherapy. Echocardiogram results, including left ventricular ejection fraction (LVEF), diastolic dysfunction, valvular disease, and any resultant treatment alterations were reviewed. Results: Three hundred twenty six patients were identified. The median (range) age was 61 (17-82) years and 62% were male. The median (range) LVEF was 65% (30-87), and 3 (0.9%) patients had LVEF < 50% (range 30-47%). Of these 3 patients, 1 had 4 vessel CABG a decade ago, his EF was 46% and treated with full dose idarubicin; 2 of them presented with blastic crisis, 1 had EF 46% and improved to 51% after 5 days and then given daunorubicin, the other one had an EF of 30% and treated with 50% dose reduced cytarabine alone. Sixty five (23%) patients had previous chemotherapy or radiation exposure, including 24 (7.4 %) with previous anthracycline, 14 (4.3%) had prior radiation to the chest wall. No patient with previous chemotherapy or radiation exposure had a reduced LVEF. Conclusions: Echocardiography prior to anthracycline therapy rarely detects abnormal LVEF. Screening echo may be helpful in those presented with leukemic blastic crisis or had previous exposure to chemo-radiation.
BST-236
Authors: Zuckerman Tsila , Ram Ron , Ben Yakar Ruth , Gengrinovitch Stela , Flaishon Liat , Rowe Jacob
Published: September 2018

e18520

Background: Cytarabine, the first-line treatment for acute myeloid leukemia (AML), is associated with severe toxicity and high treatment-related mortality (TRM), especially in older patients. Hence, while AML incidence increases with age, advanced age and comorbidities limit cytarabine administration. BST-236 is a new cytarabine pro-drug, enabling delivery of high dose cytarabine to leukemia cells with lower systemic exposure to the free drug. The aim of this study was to evaluate the safety and optimal BST-236 dose in acute leukemia patients. Methods: A Phase I/IIa prospective open label study enrolled adult relapsed/refractory or newly-diagnosed acute leukemia patients. Patients are enrolled into 6 BST-236 escalating-dose cohorts (0.3 – 6 g/m2/d). Treatment was administered as 1-hour daily infusion for 6 days. To date, 18 patients, median age 77 (27-90), were treated with up to 4.5 g/m2/day: 6 relapsed/refractory AML patients, median age 64 (27-81), and 12 newly-diagnosed, unfit for standard chemotherapy patients (7 secondary AML; 5 de novo AML/ALL), median age 79 (70-90). Results: BST-236 treatment was well-tolerated. Only 6 SAEs were assessed as possibly/probably related to BST-236, all “on-target” hematological toxicity events or bacterial infections. The 8-weeks TRM (including from disease progression) in the newly-diagnosed population was 16%. No neurological events or > grade 2 typical cytarabine events such as mucositis, diarrhea, or alopecia were reported during treatment or within 30 days of follow up. Response to the treatment was observed in 6 of the 12 newly-diagnosed patients, including 4 complete remissions (CR), with increased overall survival (OS). No response was reached in the relapse/refractory patients. Conclusions: BST-236 is safe and very well tolerated, enabling delivery of high dose cytarabine to old patients, resulting in overall response and CR rates of 50% and 33%, respectively and increased OS. Notably, 67% of the responding patients had secondary AML, refractory to hypomethylating agents. A phase II study is planned to confirm these encouraging results. Clinical trial information: NCT02544438.
Treatment patterns and characteristics of acute promyelocytic leukemia (APL) patients receiving arsenic trioxide (ATO) therapy in a real-world setting.
Authors: Tang Boxiong , Gabriel Susan , Zhou Jifang , Pathak Ashutosh K. , Irwin Debra , Riehle Ellen , Lo-Coco Francesco , Tallman Martin S.
Published: September 2018

e18522

Background: Clinical trials have shown that low-risk APL patients had significantly better outcomes when receiving first-line all-trans retinoic acid (ATRA) + ATO compared with standard ATRA + chemotherapy. Few published studies have used real-world data to describe patients using ATO and their current treatment patterns. This study used United States (US) administrative claims data to describe treatment patterns and characteristics of patients receiving first-line ATO. Methods: This retrospective, observational cohort study used claims data from the MarketScan databases. As there is no ICD-9-CM diagnosis code for APL, ATO treatment was used as a surrogate for the diagnosis of APL since ATO is typically used only in APL patients. Patients were selected if they had ≥1 claims for ATO between January 1, 2000, and June 30, 2015. Date of first use was designated the index date. To identify first-line ATO initiation, patients with ATRA or other APL-indicated chemotherapy claims any time before the index date were excluded. Variable baseline and follow-up periods consisting of ≥3 months of pre-index and ≥30 days of post-index continuous enrollment in medical and pharmacy benefit were used. Results: In total, 331 patients were identified with a subset (n = 265) having ≥2 claims for ATO. The analysis focused on these 265 patients, 54% of whom were male. Mean age was 60.6 years; 45% were covered by Medicare. The most common comorbid conditions measured were diabetes (6%), chronic obstructive pulmonary disease (5%), and congestive heart failure (4%). The most commonly selected APL treatments administered during follow-up were ATRA (17%) and daunorubicin (9%) with the use of idarubicin, cytarabine, and mitoxantrone at less than 3%. Maintenance therapy with methotrexate or 6-mercaptopurine was observed in 7% and 6% of patients, respectively. Conclusions: This is one of the first studies to examine patient characteristics and treatment patterns for first-line ATO using real-world data. Further research is needed to evaluate outcomes for patients receiving ATO as first-line therapy and to re-evaluate treatment guidelines in light of these outcomes.
Allogenic stem cell transplant in patients over the age of 70, including octogenarians, with hematologic malignancies: A single institution experience.
Authors: Gaudet Robert E. , Cerny Jan , Ramanathan Muthalagu , Raffel Glen , Zhou Zheng , Shanahan Lindsey , Bednarik Jayde , Nath Rajneesh
Published: September 2018

e18538

Background: Patient age is an important factor when considering allogenic stem cell transplant (aSCT) as a treatment modality for hematologic malignancies. Previous series exploring older age and outcome in aSCT have generally not included fit, older adults beyond the age of 80: a group typically considered ineligible for aSCT. This report describes our single-institution experience with aSCT in patients age 70 and older, including octogenarians, from March 2010 through April 2016. Methods: Retrospective analysis was performed on all patients older than 70 years undergoing aSCT at UMass Memorial Medical Center (UMMMC) between March 2010 and April 2016. The study was approved by the UMMMC IRB. Results: 32 patients were identified: 19 men and 13 women. 1 patient underwent a second aSCT in the study period. Median age at time of aSCT was 73 years (range 70-83). 4 patients were age >80. Diseases treated were AML (19 pts.), MDS (12 pts.), and CLL (1 pt.). 24 transplants were performed with unrelated donors: 17 with 10/10 match, 3 with 11/12 match, 3 with 10/12 match, and 1 with 9/12 match. 9 were performed with umbilical cord blood units. Grade II-IV acute GVHD developed in 9 patients (27%). Day 100 survival by age following the transplant were 11/18 (61%) for patients aged 70-75, 6/10 (60%) for patients aged 75-80 and 4/4 (100%) for patients aged 80-85. Conclusions: Allogenic Stem Cell Transplant is a viable treatment modality in highly-selected elderly patients with hematologic malignancies. Further studies are warranted in a prospective fashion. [Table: see text]