bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic analysis of prophylactic granulocyte colony-stimulating factor (G-CSF) use based on a risk model for neutropenic complications in breast cancer patients receiving adjuvant chemotherapy
Authors: Dale D. C. , Cosler L. E. , Wolff D. A. , Culakova E. , Poniewierski M. S. , Crawford J. , Lyman G. H. 
Published: March 2020

6107 Background: Although recent economic analyses of prophylactic G-CSF provide cost saving febrile neutropenia (FN) risk estimates of approximately 20%, many regimens have reported rates <20%. A prospective nationwide cohort study was undertaken to develop risk models for neutropenic complications (NC) including severe and febrile neutropenia in patients receiving cancer chemotherapy (Lyman ASCO 2005). A cost-effectiveness model is presented to evaluate the economic impact of G-CSF prophylaxis based on the model. Methods: Data on 974 consecutive breast cancer patients receiving adjuvant chemotherapy at 115 randomly selected practice sites were analyzed. The clinical and cost impact of G-CSF prophylaxis in high-risk patients based on the model was compared with: 1) no G-CSF; 2) primary prophylaxis; and 3) secondary prophylaxis. Pegfilgrastim costs were based on Medicare pricing while hospitalization costs and mortality on national hospitalization data. Results: Independent predictors of first cycle NC included: type and schedule of chemotherapy, diabetes, elevated bilirubin, planned RDI >85%, low glomerular filtration rate and low neutrophil count. Prophylactic G-CSF was associated with a decreased risk. Model R2=0.327 and c-statistic=0.80 [95% CI: 0.78–0.83; P<.001]. At a baseline FN risk of 8.4% per cycle, the expected costs over four cycles of chemotherapy were: no pegfilgrastim: $1,285; primary prophylaxis: $2,573; secondary prophylaxis: $2,040 and model-targeted G-CSF: $1,527. Expected cost varied with FN risk and model performance. Primary prophylaxis was associated with lower cost than no prophylaxis at FN risk >18%, while the model outperformed both strategies at an FN risk >10%. At a baseline cycle risk of FN of 8.4%, model-guided G-CSF was associated with an expected cost of $44,980 per life saved. Cost savings increased as model discrimination increased. The model was consistently associated with lower cost compared to secondary prophylaxis. Conclusions: A risk model for NC has been developed in breast cancer patients receiving adjuvant chemotherapy. Use of the model to guide G-CSF support appears to be cost-effective at an overall FN risk of 10%. [Table: see text]
How much missing data is too much? A single study exploration
Authors: Dueck A. , Atherton P. , Tan A. , Sloan J. 
Published: March 2020

6116 Background: Analyses of patient-reported outcomes rely on the dependability of patients to complete and submit assessments in a timely manner – not all data is obtained. In recent work focusing on quality of life (QOL) data and imputation, it has been found that most methods do not alter study results. But how much data can be missing before study results are affected? Methods: Missing data was investigated using a 2-arm study (109 patients) who completed Linear Analogue Self Assessments at 4 intervals. Patients (11%) had missing data at the second interval. Existing data was analysed for differences in scores between arms, then cases were randomly deleted to create increasing percentages (12%-20%) of missing data. Ten simulations were conducted per percent. Imputation methods applied were carrying forward the last value (LVCF), average value (AVCF), and maximum value (MVCF). Student’s t-tests were performed between arms for each simulation. Results: Imputation did not alter results of our study data which was statistically significant (SS) between arms for overall QOL (p=0.036) and spiritual well-being (SWB) (p=0.006), and not statistically significant (NS) for mental well-being (MWB) (p=0.174). After data deletion and t-test calculations, AVCF did not impact results. For overall QOL, data deletion changed the p-value to NS in 1 of 10 simulations starting at 12% missing data and 5 of 10 simulations starting at 16% missing data. No matter what percentage of missing data, imputation produced a SS p-value over 80% of the time. Data deletion and subsequent imputation did not affect the study decision for SWB. For MWB, all differences between arms were NS prior to imputation. After imputation, there was at most a 7% disagreement in conclusions. LVCF and MVCF performed equally in all simulations. Conclusions: For this particular study, when p-values are close to the study-defined alpha, the increase in missing data can change the study results and imputation methods are more likely to determine SS differences. The further the p-values are from the study alpha, there is little effect from increasing missing data or applying imputation. These results are for one particular study and further research is needed. No significant financial relationships to disclose.
Survival and cost-effectiveness of docetaxel (D) and paclitaxel (P) in patients with metastatic breast cancer (MBC): A population-based evaluation
Authors: Vu T. T. , Ellard S. , Olivotto I. , Taylor S. C. , De Lemos M. L. , Speers C. , Kuik K. , Hu F. 
Published: March 2020

6117 Background: A randomized comparison between P and D for MBC reported that overall survival (OS) was significantly superior for D (Ravdin, et al). We report a population-based comparison of P (3-hour infusion) to D (1-hour infusion) in MBC patients with prior exposure to anthracycline in terms of OS and cost-effectiveness (CE). Methods: Data on MBC patients treated with single-agent P or D (January 1999 - December 2002) were retrospectively reviewed. OS, defined as time from initiation of taxane to death from any cause, was compared using a 2-tailed log-rank test and expressed as Kaplan-Meier plots. A CE analysis, including cost of drug (list price $CDN), labour and supplies, was performed using median cost/patient and median OS (MOS). Incremental CE ratios (ICERs) were compared in a sensitivity analysis varying MOS to the extremes of the 95% confidence interval (95% CI). Results: 435 patients met eligibility criteria. MBC prognostic factors were balanced between D and P groups ( table ). MOS was significantly longer for D vs. P. (10.9 vs. 8.3 months; HR 0.76; 95% CI, 0.62 to 0.92; P = 0.006). The median number of cycles administered were 4 (D) and 3 (P). The respective cost/month of MOS is $805 (D) and $303 (P). The ICER of D vs. P was $2,434/month MOS gained. The range of ICERs in the sensitivity analysis was $1,121 to 7,361/month MOS gained. These results were robust except that P dominates when the low end of the 95%CI of MOS for D is compared to the high end for P. Conclusion: This population-based study corroborates the randomized trial’s conclusion that for patients with metastatic breast cancer, D provided superior survival compared to P. Each additional month of survival had an incremental cost of $2,434. [Table: see text] [Table: see text]
Patient characteristics influencing quality of life in gynecologic cancer
Authors: Gil K. , Frasure H. , Jenison E. , Hopkins M. , Von Gruenigen V. 
Published: March 2020

6132 Background: The Functional Assessment of Cancer Therapy general (FACT) questionnaire was developed to assess disease and treatment specific issues affecting patients’ quality of life (QoL). Factors other than cancer and its treatment, such as age, general physical and emotional health, and socio-economic status, may have significant effects on QoL and patients’ response to treatments. This study examined the effect of these variables on the domains of the FACT in gynecologic oncology patients undergoing surgery for pelvic mass suspected to be malignant or endometrial cancer. Methods: Demographic information and patient characteristics were obtained pre-operatively. Patients also completed the FACT and the SF-36, a general health questionnaire that measures physical and mental well-being but is not designed to be sensitive to the detection of small treatment effects. Correlation and multiple regression analysis were used to assess the effect of diagnosis, age, body mass index (BMI), educational level, marital status, smoking status, physical (PCS) and mental (MCS) summary scores of the SF-36 on FACT domain scores. Results: Data were collected on 157 women at their pre-operative visit (endometrial cancer, n=45; benign masses, n=79; ovarian cancer, n=33). PCS, MCS and age were positively correlated with scores on the FACT, while BMI and smoking were negatively correlated ( Table ). Educational level was negatively correlated with scores on the social domain but positively correlated with physical scores on the FACT. PCS and MCS accounted for a significant amount of the variance (R2) in regression models for each of the FACT domains ( Table ). Conclusion: Patients’ QoL, as measured by a questionnaire that is sensitive to their disease and treatment, is affected by their baseline characteristics. As treatment options become more complex, these variables are likely to be of increasing importance in evaluating QoL. [Table: see text] No significant financial relationships to disclose.
Circulating tumor cells (CTCs) in metastatic breast cancer: Biological value beyond tumor burden
Authors: Cristofanilli M. , Guarneri V. , Valero V. , Fritsche H. A. , Broglio K. R. , Reuben J. M. , Lara J. , Krishnamurthy S. , Hortobagyi G. N. 
Published: March 2020

615 Background: The detection of circulating tumor cells (CTCs) can predict progression-free (PFS) and overall survival (OS) in patients with metastatic breast cancer (MBC). We evaluated the prognostic significance of baseline CTCs in relation to standard measures of tumor burden. Furthermore, we assessed if the prognostic value of CTCs was related to any particular molecular phenotype. Patients and Methods: One hundred twenty-three consecutive MBC patients (pts) evaluated prospectively between 12/2000 and 5/2005 were included in this analysis. CTCs from 7.5 mL of whole blood were isolated and enumerated using CellSearch system. Prognostic value was determined by analyzing the following factors, baseline level of CTCs (negative: <5 CTCs/7.5 mL; positive: ≥ 5 CTCs/7.5 mL), age (50 yrs<vs. >/=50 yrs), hormonal receptor (HR), Her-2/neu status, metastatic site (visceral vs. non-visceral), Swenerton score, CA27.29 levels, and previous chemotherapy for MBC (none vs. pre-treated), Results: Median age was 52 years (range 24–88) and the median follow-up was 7.7 months (range 0–53.4 months). The median OS for the alive pts was 17.5 months. Fifty-two pts (42%) had positive CTCs and abnormal CA27.29 was detected in 80 pts (66%). The median OS for patients with negative vs. positive CTCs were 28.3 months (range 1.28 - 31.24) and 12.8 months (range 1.71 to 36.83) respectively (p=0.0001). In the multivariable model, HR status, CTCs, and CA27.29 level were the only factors significantly related to OS. CTCs demonstrated the strongest predictor for OS and were associated with 2.53 times the risk of death (p = 0.003). The prognostic value of CTCs was independent of line of treatment, site of recurrence and phenotype of the disease. Conclusions: CTCs demonstrated prognostic value independent of standard measures of tumor burden and phenotypic characteristics of the disease. CTCs are an important marker of tumor biology in metastatic breast cancer. No significant financial relationships to disclose.
Safety analysis from PACS 04—A phase III trial comparing 6 cycles of FEC100 with 6 cycles of ET75 for node-positive early breast cancer patients, followed by sequential trastuzumab in HER2+ patients: Preliminary results
Authors: Spielmann M. , Roché H. , Delozier T. , Romieu G. , Bourgeois H. , Serin D. , Canon J. , Asselain B. , Roca L. , Genève J. 
Published: March 2020

632 Background: Following the BCIRG 001, PACS 01 and HERA trials, this randomised, multicentre, open-label, Phase III trial was designed to demonstrate the benefit of concomitant docetaxel and epirubicin versus anthracyclines, and evaluate the use of sequential trastuzumab. Methods: Patients (pts) with localised, resectable, unilateral breast cancer who met the following criteria were eligible: age <65 years, ≥1 positive node, M0, adequate heart and organ functions. Pts were randomised to receive either 6 cycles of 5-fluorouracil-epirubicin-cyclophosphamide (FEC100: F and C, 500 mg/m2, E 100 mg/m2) (Arm A) or epirubicin-docetaxel (ET75: E 75 mg/m2, T 75 mg/m2) (Arm B). Primary prophylaxis with G-CSF was not planned. Radiotherapy was mandatory after conservative surgery and tamoxifen was required in pts with hormone receptor-positive tumours. Pts with HER2-positive disease were then further randomised to observation only or to 1 year of trastuzumab monotherapy (6 mg/kg iv every 3 weeks). In HER2-positive pts receiving trastuzumab, left ventricular ejection fraction (LVEF) was determined at Cycles 2, 4, 8, 13, 18 and after 2 years. Otherwise, LVEF was determined at baseline and at 1 year post-surgery. Results: Of the 3010 pts recruited (2622 evaluable for safety to date), 1518 received FEC100 and 1492 received ET75 after the first randomisation. Haematologic toxicity was the most frequent toxicity in both arms. Grade 3–4 toxicities were similar for Arms A and B, except febrile neutropenia (10.3% and 31.4%, respectively) and nausea/vomiting (13.2% and 7.5%, respectively). Grade 2 clinical cardiac toxicity (decreased LVEF) was observed in 4 pts in Arm A and 5 in Arm B, with median LVEF scores of 63% in both arms at the end of chemotherapy. HER2-positive pts (n=500) were then randomised to either receive trastuzumab (n=259) or observation only (n=241). Conclusions: These preliminary safety data indicate that FEC100 and ET75 were both well tolerated, with acceptable cardiac safety values. The trial is ongoing and further analysis regarding the use of trastuzumab in this setting will be presented. [Table: see text]
PIK3CA mutations in breast cancer: A potential predictive marker
Authors: Santarpia M. , Altavilla G. , Margeli M. , Mesiti M. , Cavallari V. , Cirauqui B. , Reguart N. , Barnadas A. , Taron M. , Rosell R. 
Published: March 2020

639 Background: Somatic mutations in phosphoinositide-3-kinase catalytic alpha (PIK3CA) activates Akt, attenuates apoptosis and promotes tumor invasion. The common mutations E545K and H1047R confer resistance to paclitaxel in immortalized breast cancer cell lines. We screened primary breast cancers for PIK3CA mutations in the helical and catalytic domains. Methods: Tumor samples from 61 stage I-III breast cancer patients treated with adjuvant chemo- and/or hormone therapy were examined for PIK3CA mutations E542K, E545K and H1047R by the 5-nuclease assay (TaqMan) using the ABI Prism 7900HT Sequence Detection System. Results: Mutations were found in 17 patients (27.9%): 6 E542K; 5 E545K; 6 H1047R. PIK3CA mutations were not associated with expression of estrogen or progesterone receptors, lymph node metastases, or ERBB2 overexpression. (See table ) Conclusions: PIK3CA mutations occur frequently in breast cancer and could be a novel predictive marker of chemoresistance and an appealing target for therapeutic inhibition, independent of hormone receptors and ERBB2 status. [Table: see text] No significant financial relationships to disclose.
Treatment outcome after induction chemotherapy before allogeneic hematopoietic SCT in patients with advanced MDS
Authors: Ramos C. A. , Jakubowski A. A. , Boulad F. , Papadopoulos E. B. , Young J. W. , Kernan N. A. , Perales M. A. , Small T. N. , Berman E. , O’Reilly R. J. , Castro-Malaspina H. R. 
Published: March 2020

6502 Background: The need for induction chemotherapy (IC) before allogeneic hematopoietic stem cell transplant (alloSCT) in advanced myelodysplatic syndrome (MDS) remains controversial. Methods: This is a retrospective analysis of the remission rate in 99 patients with advanced MDS (≥5% marrow blasts) and acute myeloid leukemia (AML, ≥ 20% blasts) evolving from MDS, who were treated with IC before receiving cytoreduction for SCT. These patients were referred to MSKCC for alloSCT from 6/1980 to 10/2004, and subsequently underwent an unmodified or T cell-depleted (TCD) SCT from a matched or mismatched related or unrelated donor after myeloablative cytoreduction in the majority. Results: All patients had MDS at diagnosis: 33% had high risk (HR), 22% intermediate risk (IR) and 42% good risk (GR) cytogenetics; 38% had HR, 32% IR-2 and 25% IR-1 IPSS. The median age was 43 (range 2–66). 76% had primary and 24% had secondary MDS (chemotherapy or radiation). At the time of IC, 64% had frank AML, 33% RAEB-1 and 2, and 3% CMML-2. A combination of an anthracycline (Ac) and standard dose (SD) cytarabine (AraC) was administered to 53% of the patients. Other regimens included Ac with high dose (HD) AraC (15%), Ac with SD AraC and etoposide (15%), HD AraC alone (8%), and HD AraC with etoposide (4%). 26% of patients required a second line regimen and 4% went on to a third. None of the patients died of complications due to IC. CR was achieved in 60% of patients overall (64% in those receiving Ac + SD AraC ± etoposide and 52% for HD AraC ± Ac ± etoposide). The CR rate was 65% in primary and 42% in secondary MDS, and was similar in adults (60%) and children (56%). CR rates were 44% in HR, 68% in IR, and 65% in GR cytogenetics; 58% in HR, 59% in IR-2, and 60% in IR-1 IPSS. According to disease status at IC, the CR rate was 60% for RAEB-1 and 2 and 59% for AML. 12% of complete responders relapsed prior to cytoreduction for SCT. 49% of all patients underwent a TCD SCT from an HLA identical sibling. There are no long term survivors after SCT in patients who did not achieve CR after IC, in contrast to 47% overall survival at 10 years for responders. Conclusions: IC in advanced MDS is associated with a high rate of CR. IC before cytoreduction for SCT is an effective approach to reduce the burden of disease particularly prior to TCD SCT. No significant financial relationships to disclose.
Dasatinib in patients with chronic phase chronic myeloid leukemia (CP-CML) who are resistant or intolerant to imatinib: Results of the CA180013 ’START-C’ Study
Authors: Hochhaus A. , Kantarjian H. , Baccarani M. , Cervantes F. , Facon T. , Goldberg S. , Erben P. , Countouriotis A. , Ezzedine R. , Druker B. J. 
Published: March 2020

6508 Background: Dasatinib (BMS-354825) is a novel, oral, multi-targeted kinase inhibitor of BCR-ABL and SRC kinases with proven preclinical and clinical activity against imatinib resistant BCR-ABL mutations. Methods: CA180013 is an open-label Phase II study of dasatinib in imatinib-resistant (IM-R) or -intolerant (IM-I) patients (pts) with CP-CML. Between February-August 2005, 424 pts were recruited from 75 centers worldwide. Dasatinib was given at 70 mg twice daily (BID) with dose escalation to 90 mg BID in pts lacking response, and dose reductions to 50 and 40 mg BID for toxicity. Evaluations were weekly blood counts for the first 12 weeks; bone marrow cytology and cytogenetics every 3 months. The primary endpoint was rate of major cytogenetic response (MCyR; ≤35% Philadelphia pos. metaphases) in IM-R pts. Results: Data are currently available from the first 186 pts (127 IM-R, 59 IM-I) accrued prior to May 12, 2005. Median age was 59 yrs (range 24–79); 46% were male. Median time from diagnosis of CML was 64 months. Of the IM-R pts, 72% received IM >3 yrs, and 72% had >600 mg/day of IM. Overall, 70% had received prior interferon alpha. 62 (33%) pts achieved a prior MCyR to IM. With ≥6 months of follow up, 168 (90%) pts had a complete hematologic response (CHR). MCyR were achieved in 83 (45%) pts including 40 (31%) of IM-R pts, and 43 (73%) of IM-I pts. Mutations in the BCR-ABL domain were found in 65/176 (37%) pts; 57 (88%) achieved CHR, and 24 (37%) MCyR. Molecular response analysis is ongoing. 160 (86%) pts remain on study without progression. Grade 3/4 neutropenia or thrombocytopenia was reported in 83 (45%) pts and 85 (46%) pts with onset after 4–8 weeks of therapy in most pts. Temporary dose interruptions occurred in 146 (78%), and dose reductions in 96 (52%) pts with a median daily of 108 (range 19–169) mg. Non-hematologic toxicity consisted mainly of Grade 1/2 diarrhea, headache, superficial edema, and pleural effusion, with ≤2% Grade 3/4. There was no cross-intolerance between dasatinib and IM. Conclusions: Dasatinib demonstrated substantial hematologic and cytogenetic activity in IM-R and IM-I pts with CP-CML. An updated analysis of 424 pts with ≥6 months of follow up will be presented. [Table: see text]
Phase II study of lenalidomide (CC-5013) for patients with myelofibrosis
Authors: Verstovsek S. , Cortes J. , Thomas D. , Beran M. , Koller C. , Giles F. , Kantarjian H. 
Published: March 2020

6510 Background: Lenalidomide (CC-5013, Revlimid), analogue of thalidomide, a new drug in a group known as ImiDs, with broad cytokine modulatory activity. Lenalidomide is less toxic than thalidomide without teratogenicity, sedation, or neurotoxicity, and is 50,000-fold more potent in inhibiting, tumor necrosis factor-α, that is involved in the pathophysiology of myelofibrosis (MF). Patients (pts) with MF currently have no approved standard effective therapy. Methods: Phase II study of lenalidomide for MF pts with plts >30×109, performance status ≥3, total bilirubin and creatinine of <3mg/dL, accrued 41 pts. Pts with prior hypersensitivity to thalidomide excluded. Pts received lenalidomide 10mg orally daily (5mg if platelets <100x109). Median age 65 (range, 42–83). 36 pts (88%) had received prior therapy for MF, including thalidomide 13 (32%), hydroxyurea 13 (32%), interferon 11 (27%), anagrelide 10 (24%), and erythropoietin 6 (15%). Baseline hemoglobin was <10g/dl in 19 (46%) (13 or 32% were transfusion dependent), platelets <100x109 in 12 (29%), absolute neutrophils <1.5x109 in 2 (5%), 20/34 (59%) had splenomegaly (median 10cm BCM, range 1–30; 7 with prior splenectomy), and 17 (42%) had cytogenetic abnormality. Results: Median follow is 5 months (range 1–14). Therapy has been well tolerated. Most common toxicities of any grade were rash 6(39%) and pruritus 9 (22%). Grade ≥3 toxicities were neutropenia 13 (32%), thrombocytopenia 11 (27%), fatigue 3 (7%) and rash 2 (5%). 8 (20%) pts required dose reduction; 4 discontinued therapy due to toxicity. Responses have been observed in 19 (46%) pts. These include CR 3(7%; normalization of hemoglobin and WBC), PR 5 (12%; improvement in platelets and hemoglobin ± spleen), and hematologic improvement 11 (27%) pts (improvement in platelets - 4, spleen - 2, WBC - 4, BM blasts - 1). 5 of 13 transfusion-dependent pts have become transfusion-independent. 6 of 12 (50%) pts with platelets <100x109 improved the count by >50%. Median time to response was 6 wks (range 1–22). Responses have been sustained for a median of 31+ wks (range 1+-40+). Conclusions: Lenalidomide has clinical activity in a subset of pts with MF with an acceptable toxicity profile. Studies using lenalidomide in combination with other agents are planned. No significant financial relationships to disclose.