bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential budget impact of capecitabine versus 5-FU/LV as adjuvant chemotherapy for stage III (SIII) colon cancer in Canada and its provinces
Authors: Virik K. , Skedgel C. , Younis T. 
Published: March 2020

6581 Background: Adjuvant chemotherapy for SIII colon cancer is an accepted standard of care. Oral Capecitabine (CAP) has been shown to be at least equivalent and possibly superior to 5FU/LV (Mayo regimen) with regards to a superior relapse free survival. This new option is associated with a higher drug cost but improved toxicity profile and appears to be cost-effective (CE). An economic analysis was undertaken to examine the potential budget impact for CAP in Canada and its provinces for 2007 onwards. Methods: A previously developed cost-effectiveness model was adapted to a prevalence perspective to project the net budgetary impact of CAP over a 5 year horizon. The projected population and incidence of colon cancer for each Canadian province from 2007–2016 was obtained and the proportion of patients with SIII colon cancer suitable for adjuvant chemotherapy was estimated from the literature. The average budget impact in the first 5 years (start up phase) and subsequent years (steady state) was assessed in Canadian $. Results: The projected average annual impact for Canada is 13.9 million (M) during the start up phase and $11.8 M during the steady state phase (NL $210K, PEI $63K, NS $424K, NB $282K, QC $2.92M, ON $4.66M, MB $464K, SK $336K, AB $993K and BC 1.45M). Budget impact is greater during the initial start-up phase (2007–11), as the steady state impact (2012–16) includes relapses avoided over a 5-year period. Sensitivity analyses for key parameters will be provided. Conclusions: The annual budget impact of CAP decreases over time and reaches a steady state after 5 years when the full impact of decreased recurrences is captured. As CAP appears to be CE, budget impact analysis has the potential to assist in the planning of healthcare funding resources regarding this treatment option. [Table: see text]
Identifying patients at high risk for neutropenic complications during chemotherapy for metastatic breast cancer (MBC) with doxorubicin or pegylated liposomal doxorubicin: Development of a prediction model
Authors: Reardon G. , Rayson D. , Chang J. , Gelmon K. , Dranitsaris G. 
Published: March 2020

6598 Background: Despite the effectiveness of anthracycline (ACH) therapy in the adjuvant and MBC settings, neutropenic complications (NC) remain a common and often unpredictable problem. Consequences may include dose reductions or delays in chemotherapy, or hospitalization for fever or infection. This study describes the development of a cycle-based risk prediction model for NC during chemotherapy with traditional doxorubicin (DOX) or a pegylated liposomal formulation (PLD) for MBC. Methods: Data analyzed was from a randomized clinical trial of MBC patients (n=509), who received chemotherapy with DOX (60 mg/m2 every 3 wks) or PLD (50 mg/m2 every 4 wks) [O'Brien, 2004]. NC were defined as an absolute neutrophil count (ANC) = 1.5 x106 cells/L, febrile neutropenia or neutropenia with infection. Patient, treatment and hematological factors potentially associated with NC were evaluated. Factors with a p-value of ≤ 0.25 within a cycle were included in a generalized estimating equations (GEE) regression model. Using backward elimination, we derived a risk scoring algorithm (range 0–63) from the final reduced model. Results: Risk factors retained in the model included poor performance status, ANC = 2.0 × 106 cells/L at some point in the previous cycle, the first cycle of chemotherapy, DOX vs. PLD and older age. A precycle risk score from = 25 to < 40 for a given patient was identified as being the optimal threshold for sensitivity (58.0%) and specificity (78.7%). Patients with a score at or beyond this threshold would be considered at high risk for developing NC in later cycles. Risk scores below, within, or above this threshold predict a 0.3%–2%, 3%–8% and a 9%–45% probability risk of NC, respectively. Conclusion: This risk prediction tool demonstrated acceptable internal validity and can be readily applied by the clinician prior to a given cycle of chemotherapy. The application of this prediction tool may allow for identification and targeted intervention (such as growth factor support or the use of PLD) for those most likely to experience NC during anthracycline-based chemotherapy for MBC. No significant financial relationships to disclose.
The quality-of-life impact of osteonecrosis of the jaw: Implications for bisphosphonate use in metastatic breast cancer
Authors: Miksad R. A. , Come S. , Weinstein M. 
Published: March 2020

6620 Background: Osteonecrosis of the jaw (ONJ) has been linked to bisphosphonates used to prevent skeletal related events (SREs) in metastatic breast cancer (MBC). The primary aim of this decision-analysis study is to determine the preference threshold at which the quality of life (QOL) impact of ONJ may change bisphosphonate treatment decisions. Methods: We developed a Markov decision- analysis model of bisphosphonate use in MBC that includes the risk of ONJ. For the base case we estimated the QOL impact of ONJ by evaluating published ONJ reports with the Oral Health Impact Profile (OHIP). OHIP scores were transformed to EQ5D utilities and adjusted for MBC (published utility for MBC=0.63). We used published utility values for SRE: 0.46 for the month in which SRE occurs. Based on published data, we estimated that bisphosphonates reduce the incidence of SREs by 41% and that the incidence of SRE rises with increased bisphosphonate exposure: year 1=0.004/month; year 2=0.022/month; year 3=0.034/month. We inspected 2 treatment strategies: treat all patients with bisphosphonates (treat all) and treat no patient with bisphosphonates (treat none). Results: 18 published cases were adequate for evaluation. The mean OHIP score=27 (possible range 14–70), s.d.=1.8. We calculated that patients with MBC and ONJ have a utility=0.53 (s.d.=0.04) for the base-case. The model predicted a mean survival of 22 months for both strategies. In the treat all strategy each patient received a mean of 19 months of bisphosphonates and suffered 2.4 SREs. In the treat none strategy each patient suffered 4.0 SREs. In the base case, the treat all strategy maximized net quality-adjusted life, although by less than 1/2 month per patient. The treat all strategy was optimal for only 33% of patients. The treat all strategy does not maximize net quality-adjusted life if the risk of ONJ is 4.5 times higher than the base case or the ratio of the utility for ONJ to the utility for SRE is less than 0.4 (base-case ratio=1.152). Conclusions: The QOL impact of ONJ alters the decision to use bisphosphonates when 1) the incidence of ONJ is 4.5 times higher than published estimates; or 2) the long-term preference for ONJ is 60% lower than the short-term preference for SRE. Further QOL research may refine these estimates. No significant financial relationships to disclose.
Cost-effectiveness (CE) analysis of CHOP and rituximab for diffuse large B-cell lymphoma (DLBCL) in British Columbia (BC)
Authors: Loh G. W. , Taylor S. C. , Peacock S. , Moravan V. , Krahn M. , Sehn L. 
Published: March 2020

6623 Background: The BC Cancer Agency (BCCA) provides province-wide, population-based care. Outcomes are monitored to verify therapeutic effectiveness and justify funding for systemic treatment policies. The CE of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (CHOP-R) for DLBCL was compared to its predecessor, CHOP alone. Methods: This was a pragmatic population-based CE analysis based on the original cohort of advanced DLBCL patients described by Sehn et al (JCO 2005) who received either CHOP or CHOP-R between Sept 1999 and Aug 2002 (18-months pre and post availability of rituximab in BC) according to standard BCCA treatment policy at the time. The primary endpoint was CE in terms of life-expectancy (LE) at a median follow-up of 4 years (cost-per-life-year-gained). Costs were incorporated into a decision analysis including primary systemic therapy and downstream chemotherapy, radiotherapy, and stem-cell transplant (SCT). Actual incidence of each downstream therapy was converted to a probability for each group. Downstream therapy costs were then multiplied by these probabilities and added to the respective primary treatment costs. The CE analysis took the BCCA perspective which includes all direct costs for active cancer treatment, and hospitalization for SCT, but not ambulatory supportive care. Sensitivity analyses varying LE to the extremes of its 95% CI, modeling out to 15 years and discounting at 0, 3, and 5% were performed. Results: 292 patients were included and categorized to treatment received: 148 CHOP and 144 CHOP-R (median follow- up 5.4 and 4 years respectively). LE to 4 years was 30.18 months for CHOP and 39.44 for CHOP-R. OS at 4 years was 48.8% and 70.1% for CHOP and CHOP-R respectively (p<0.0001) Respective costs of primary and downstream therapy were $4,682 and $7,198 for CHOP versus $26,366 and $6,228 for CHOP-R. The incremental CE ratio at 4 years median follow-up was $26,844 CDN per life year gained. Results were robust across univariate sensitivity analyses conducted. Conclusions: At 4 years median follow-up, CHOP-R improves LE and appears to be economically attractive at conventional thresholds. CE is an increasingly useful tool for the BCCA in making decisions about new cancer therapies. No significant financial relationships to disclose.
Overhead costs (OC) associated with quality oncology care (QOC) monitoring to ensure compliance with national treatment guidelines (TG)
Authors: Vakil R. , Bosserman L. D. , Presant C. , McNatt W. , Der A. , Greenburg A. , Estrella A. , Upadhyaya G. , Vakil M. 
Published: March 2020

6637 Background: QOC is a goal of all oncology practices (op), healthcare insurance plans (hip), HMOs, and payers for health insurance. In order to ensure compliance with TG and maintain QOC in a multi-site op, we adapted an electronic medical record (EMR) to evaluate tumor and stage specific compliance in oncology treatments. This report evaluates the OC associated with development and operation of that monitoring system and its application to an HMO patient population of 75,000 covered lives. Methods: OC included 25% (proportion of HMO to total patients )of the emr system developmental costs (DC) and operational costs (OpC). Personnel time included entering data and treatments, training, data coordination, and data analysis. Salaries were based on regional averages for physicians, administrators, clerks, and nurses. Time estimates were made for monitoring quality data only, excluding standard patient care. Compliance data is reported separately. Results: 1,250 patients over 18 months were treated by 5 of the op physicians. DC for this program included computer hardware $25,000, personnel training $10,900, and EMR licensing $12,500. Annualized operational costs (OpC) included emr maintenance fees $1000, IT consultants $4500, physician time to enter individual patient data at first consultation and follow up visits $58,000, nursing time to enter treatment data and continued training $7650, physician continued training $11,250, senior administrator coordination $30,000, administrative supervision $17,900, clerical data analysis $22,500, and senior physician supervision $50,000. Costs per covered life for DC were $0.645 and for OC were $2.704 per year. Conclusions: The costs to maintain QOC and ensure TG compliance are substantial and must be reimbursed by hips and HMOs. Understanding these costs is essential to negotiating care contracts with hips that will monitor care appropriately. Investing in EMR methods to ensure QOC will be important to patients and op, as well as hips. Monitoring continuing OC to determine if they decrease with additional experience is essential. Standardizing EMR data sets aad op methodologies for compliance monitoring will further improve efficiencies and cost efficacy in documenting delivered QOC. No significant financial relationships to disclose.
Prognostic factors for response to second induction course in patients showing persistent disease after first course of standard induction chemotherapy for de novo acute myeloid leukemia (AML)
Authors: Lee J. , Sym S. , Choi S. , Lee J. , Lee Y. , Seol M. , Ryu S. , Lee J. , Kim W. , Lee K. 
Published: March 2020

7056 Background: Standard induction chemotherapy for AML consists of cytarabine plus daunorubicin or idarubicin (‘7+3' regimen). For patients showing persistent leukemia after first induction course (IND1) of the induction, usual practice is to give a second course (IND2) of similar regimen (‘7+3' or 5+2'). This strategy, however, has not been well evaluated. We investigated prognostic factors for response to IND2. Methods: We performed a retrospective study in 110 patients with de novo AML. All patients received cytarabine (100 or 200 mg/m2/d) for 7 days plus daunorubicin (45–60 mg/m2/d) or idarubicin (12 mg/m2/d) for 3 days as IND1. Patients who showed persistent leukemia after IND1 were given the same doses and drugs as ‘5+2’ (n = 85) or ‘7+3’ (n = 25) for IND2. We collected the clinico-pathologic data of the patients at diagnosis and at IND2, and analyzed prognostic factors for response to IND2. Results: Sixty-one (55.5%) of 110 patients, who received IND2, achieved complete remission (CR). The causes of treatment failure were resistant disease in 35, complication of aplasia in 8, and indeterminated in 6. Five-year probabilities of overall and relapse-free survival were 25% and 21%, respectively. Multivariate analysis demonstrated that cellularity at interim BM biopsy > 30% (p = 0.015), blast percentage at interim BM aspiration > 30% (p = 0.031), presence of circulating blasts at IND2 (p = 0.011), and unfavorable chromosomal abnormalities (p = 0.014) were independent risk factors for failure to induce CR. The CR rates were significantly different according to the number of the risk factors: 73% for 0–1 factor, 48% for 2 factors, and 11% for 3–4 factors (p< 0.001). Conclusions: We identified 4 independent poor risk factors for CR in patients who showed persistent disease after standard induction chemotherapy and who received similar second induction course. Other treatment strategies such as high-dose cytarabine rather than standard regimens seem to be needed for the patients with 3–4 risk factors before IND2. No significant financial relationships to disclose.
Older-age AML: Disease biology and dose response
Authors: Buchner T. , Berdel W. E. , Haferlach C. , Haferlach T. , Schnittger S. , Serve H. L. , Sauerland M. C. , Heinecke A. , Wörmann B. , Hiddemann W. 
Published: March 2020

7058 Background: In 2602 pts entering two sequential trials the 47% pts of 60+y compared to the younger pts achieved 55 vs 71% CR, 19 vs 41% OS and 77 vs 54% RR (relapse risk) at 3 years. While the trials addressed various options for both de-novo and secondary AML understanding the age related biology of AML required restriction to pts comparable in history, therapy and availability of risk factors. Methods: We therefore selected from the two trials pts with de-novo AML and known karyotype assigned to one of two different intensity induction regimens, either TAD-HAM (HAM, high-dose araC 3(age <60) and 1(age 60+) g/m2x6), or HAM-HAM. All pts received TAD consolidation and monthly reduced TAD maintenance. Results: In the 1284 selected pts the CR rate is 60% in pts of 60+y and 70% in those of 16 −<60y (p<.001), the OS is 23 vs 41% (log rank p<0.001) and the RR is 73 vs 50% (p<.001). There are advantages for younger pts in favorable (16 vs 7%) and unfavorable (18 vs 24%) karyotypes (p<.001) whereas WBC (p=.002) and LDH (p=.002) are lower in the older pts. Among normal karyotypes (52%) the favorable NPM mutation in absence of Flt3 mutation account for 33% of NPM/Flt3 combinations in older and 37% in younger pts (n.s.). The inferior CR, OS and RR in the older vs younger pts is seen in all prognostic subgroups. Thus, the OS at 3 years is 36 vs 62% in favorable (p=.001), 2 vs 14% in unfavorable karyotypes (p=.001), 25 vs 42% in low WBC (p<.001), 21 vs 38% in high WBC (p<.001), 23 vs 42% in low LDH (p<.001), 16 vs 38% in high LDH (p<.001), 30 vs 43% in low day 16 blasts (p<.001), 19 vs 38% in high day 16 blasts (p<.001) and even 50 vs 63% in pts with NPM+/Flt3- mutation (p=.020). In contrast, outcome does not vary by randomization for TAD-HAM vs HAM-HAM chemotherapy. Conclusions: The lack of dose response and the modest age related differences in defined risk profiles suggest hitherto unknown determinants of the poor outcome in older age AML across all subsets. These experiences may indicate the way toward novel experimental options instead of further escalation. No significant financial relationships to disclose.
A phase I study of the combination of a DNA topoisomerase inhibitor, idarubicin, with the histone deacetylase inhibitor vorinostat, in advanced acute leukemia
Authors: Kadia T. M. , Borthakur G. , Wierda W. , Ravandi F. , Faderl S. , Newsome W. , Zwiebel J. , Egorin M. , Garcia-Manero G. 
Published: March 2020

7066 Background: Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase inhibitor (HDACi) with single agent activity in patients with advanced leukemia. HDACi lead to the acetylation of histones and facilitate an open chromatin configuration. Idarubicin potently inhibits DNA topoisomerase (topo) II by forming stable complexes with it, and eventually leading to ds-DNA breaks and apoptosis. Because of their effect on the chromatin of dividing cells, we postulated that the pairing of an HDACi with a topo II inhibitor, would have antileukemia activity. We tested this in vitro in leukemia cell lines and have shown that the combination of idarubicin and SAHA is synergistic. Methods: To test this clinically, we developed a phase I trial of the combination of idarubicin and SAHA, given in 2 different schedules, in advanced leukemia. In schedule A, idarubicin 12 mg/m2 daily for 3 days is given concurrently with SAHA, orally TID for 14 days (starting at 100 mg). In schedule B, SAHA is only given for 3 days. Only SAHA was dose-escalated, following a classic 3+3 schema, with the plan to treat 10 patients at the MTD. If both schedules were open at any given time, patients were randomized among them. Results: So far, 20 patients have been treated: 8 in schedule A and 12 in B. Median age of the patients is 56 (21–80). Of the patients enrolled thus far, 19 (95%) had relapsed, refractory AML, 1 had MDS, and 8 out of the 20 (40%) had diploid cytogenetics. In schedule A, a dose of idarubicin at 12 mg/m2 and SAHA at 100 mg was found to be above the MTD, with the DLT's being myelosuppression, encephalopathy, and dysphagia. Dose escalation of schedule B continues currently at a dose of SAHA at 400 mg. No severe grade 3 or 4 toxicities have been observed on this schedule. No cardiac toxicity has been observed. So far, 2 CR and 2 complete marrow responses have been observed. All of these patients had failed previous anthracycline-based chemotherapy. Induction of γ-H2AX, histone acetylation, and induction of topo II and p21CIP1 mRNA expression are being evaluated, as well as pharmacokinetic characteristics of both agents. Conclusion: The combination of idarubicin with SAHA is safe and active, and SAHA could be incorporated in the treatment of front-line AML. No significant financial relationships to disclose.
Treating the anemia of MDS with erythropoietin: Impact of higher dose compared to combination with G/GM-CSF
Authors: Moyo V. M. , Lefebvre P. , Duh M. , Yektashenas B. , Mundle S. 
Published: March 2020

7082 Background: Recombinant human erythropoietin (EPO) is extensively used to improve erythropoiesis and reduce transfusions in anemic MDS pts. The addition of G/GM-CSF to EPO alfa or beta has been associated with higher erythroid response (ER) rates vs. EPO alone. Studies suggest higher ER rates could be achieved with EPO monotherapy if higher initiation doses were used. To study this question a meta-analysis was performed on studies of MDS pts treated with EPO alfa or beta + G/GM-CSF. Methods: Data extraction was performed on studies from PubMed, ASCO and ASH proceedings from 1990–2006 in MDS pts treated with EPO (alfa or beta) ± G/GM-CSF. To allow for cross comparisons, only studies including IWG or IWG-like ER criteria were selected for analysis. Pooled estimates of ER rates were calculated using fixed-effect (F-E) meta-analysis methods. Results were stratified by: (i) EPO-alfa at standard doses, (ii) EPO- alfa at high doses, (iii) EPO-alfa + G/GM-CSF, and (iv) EPO-beta + G/GM-CSF. Results: From 39 studies identified, 19 met inclusion criteria. Most pts (>55%) had RA/RARS. Studies using EPO-alfa at standard doses showed comparable ER rates to studies using EPO- alfa + G/GM-CSF (49.0% vs. 50.6%; p=0.731) ( Table ). Among EPO-alfa studies, those using higher EPO doses had higher ER rates vs. studies using standard EPO doses (p<0.001) or EPO + G/GM-CSF combination (p=0.007). Overall ER rates were not available for studies using EPO- beta + G/GM-CSF, however, 52 pts (37.7%) had major ER, similar to that observed in all EPO-alfa monotherapy studies (195/589=33.1%). Conclusions: These findings suggest increasing EPO-alfa dose may have a greater impact on ER than addition of G/GM-CSF. Further validation is warranted. [Table: see text] [Table: see text]
Correlation of high CD49d expression with disease progression and need for therapy in chronic lymphocytic leukemia (CLL) patients
Authors: Gattei V. , Bulian P. , Del Principe M. I. , Zucchetto A. , Niscola P. , Bomben R. , Dal Bo M. , Buccisano F. , Amadori S. , Del Poeta G. 
Published: March 2020

7091 Background: CD49d mediates interaction of lymphocytes with microenvironmental components. We and others reported the correlated expression of CD49d and CD38 by CLL cells, and the complementary value of these molecules in predicting overall survival for CLL patients. However, nothing is known on the relationship of CD49d with other prognosticators and its impact in predicting disease progression and need for therapy in CLL. Methods: The study includes 232 CLLs (median age 64 yrs), all characterized for Rai stages, lymphocyte doubling time (LDT), CD49d, CD38 and ZAP-70 expression, serum levels for sCD23 and beta2-microglobulin (beta2-m), IgVH mutations (139/232), cytogenetics (151/232; FISH for 17p, 11q, 13q, 12). CD49d was measured in CD19/CD5 cells by three-color flow cytometry, choosing a 30% cut-off to discriminate CD49d-low vs. CD49d-high CLLs. NCI-working group criteria were used for CLL diagnosis, progression and therapy need. Results: Median time-to-progression (TTP) was 136 and 56 months in CD49d-low and CD49d-high CLL patients (p=0.00008), respectively; similarly, median time-to-treatment (TTT) was 108 and 46 months for the same patient groups (p=0.000008). Correlations were also observed among CD49d and CD38 (p=2.2x10exp-16) or ZAP-70 (p=0.00009) expression, sCD23 serum level (p=0.0017), LDT (p=0.0037), Rai stages (p=0.019), cytogenetics (p=0.011), IgVH mutations (p=0.00008). TTT and TTP were significantly shorter in CLLs in advanced Rai stages, or with high CD38 and ZAP-70 or low IgVH mutations. Within these cases, significantly longer TTP/TTT were observed in subsets expressing low CD49d. Serum levels of sCD23 and beta2-m, LDT, and FISH analyses had also predictive value for progression and treatment in our series. Within the better prognosis groups (i.e. <70 U/ml sCD23, 12 months, or a normal karyotype), high CD49d expression identified a subset of patients with significantly shorter TTP/TTT. Overall, the capability of CD49d to predict disease progression and need for therapy was statistically significant in younger patients (<64 y.o.; 115 cases; p=0.0001), but not in those older than 64 yrs (117 cases; p=0.09). Conclusions: We propone to include evaluation of CD49d expression in the prognostic assessment of CLL patients. No significant financial relationships to disclose.