bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding among medical oncologists of the true monetary cost of therapy
Authors: Hoffman K. R. 
Published: August 2020

6629 Background: While oncologists are educated to deal with the medical complexities of their treatment, a new side effect, that of financial toxicity, has arisen over the past several years. One of the major challenges in private practice is explaining the monetary cost of treatment to the patient. Methods: 50 medical oncologists agreed to take a survey judging their knowledge of the financial cost of the treatments used in patients with the five most common tumors treated in the office: breast cancer, non-small cell lung cancer, colorectal cancer, non-Hodgkin's lymphoma, and three other commonly treated cancers: chronic myelogenous leukemia, multiple myeloma and ovarian cancer. Treatment regimens in the adjuvant and first line metastatic setting were used. Physicians were asked to calculate the cost of treatments to the patient and not the acquisition price of drugs. They were asked to calculate the cost based a patient completing their adjuvant therapy or treatment in the first-line metastatic setting, which was defined by each practicioner. If desired, this included the use of maintenance therapy. A body surface area of 1.8 M2 for men and 1.6 M2 for women was used. Results: 39 medical oncologists completed the entire survey. Of these, 11 were in solo practicie. 27/39 were in practice over 15 years, while only 4 were in practice under 5 years. In almost all cases where intravenous or oral targeted therapies were used, the physicians under-estimated the actual cost of treatment to the patient by 25–40%. When ‘conventional‘ intravenous chemotherapy was used, they were either correct or over-estimated the cost of treatment by 25 to 33%, especially when generic substitution of trade name drugs were available. More importantly, the actual dollar difference was up to $50,000 when targeted therapies were in the treatment regimen but only around $5,000 when conventional treatments were considered. Nearly all the physicians were ‘within the ballpark‘ when dealing with the cost of oral medications. Conclusions: Medical oncologists have a poor understanding of the monetary costs of the newer treatments they are prescribing. More education is needed in the economics, including monetary cost-benefit analysis, of oncology practice so that we can better serve our patients and society. No significant financial relationships to disclose.
A novel copay foundation assistance support program for patients receiving cancer therapy in cancer centers
Authors: Rajurkar S. P. , Presant C. , Bosserman L. , McNatt W. 
Published: August 2020

6630 Background: With advent of newer CT (biotherapy, chemotherapy, and supportive care) treatment is becoming increasingly expensive for cancer pts. Pts enrolled with Medicare and commercial insurance plans often have large copay requirements with each treatment cycle. Often, these pts undergo significant financial hardship and some pts decline treatment. We have developed a novel support program to coordinate all copay assistance foundations (FDNs) in order to secure financial assistance to facilitate appropriate CT. Methods: In September, 2008 in our multi-site cancer center (11 oncologists, 6 CT sites), we developed a dedicated support program to coordinate pt applications to copay assistance FDNs including Healthwell, Cancer Care, Patient Access, Chronic Disease Fund, Beckstarnd Cancer, Lilly Cares, and Leukemia and Lymphoma Society. Pts requesting assistance with CT copay were enrolled in this program. A dedicated staff individual obtained information about diagnosis, insurance, income level, CT plan and associated co-pay requirements. Data was given to FDNs who determined the amount of monetary assistance. Responses of FNDs and administrative costs were analyzed. Results: Of 264 pts started initiating CT between September 2008 and December 2008, 25 (9.3%) requested assistance for either IV or PO treatments. The average interval between the submission of FDN application and date of determination of assistance was 10 days. Out of 83 applications (3.32 applications/pt), 50 (60%) were approved. Ultimately 22/25 pts received FDN support of $113,475. The most common reasons for denial were if the pt's income exceeded a certain level, exclusion of coverage of certain medications and the FDN being out of funds. The administrative costs associated with this program were $18,000/yr ($720/pt, or $217/application). Administrative costs were 1.64% of approved support. More difficulties were encountered with applications for oral CT than IV CT. Conclusions: Copay for CT drugs is a financial hardship for a significant number of pts. Coordinated resources must be provided and reimbursed to facilitate appropriate and sustainable cancer care. This program is a successful model for other centers. No significant financial relationships to disclose.
Off-label chemotherapy use in a military treatment facility
Authors: Powers J. F. , Osswald M. B. 
Published: August 2020

6631 Background: Off-label prescribing of chemotherapeutics is thought to be frequent but scant data exist to quantify its occurrence. The few studies evaluating off-label drug use in oncology show that the frequency ranges from 6.7% to 75%. This is the first known evaluation of oncology prescribing practices in a military treatment facility. Methods: After approval by the institutional review board, all outpatient chemotherapy orders from 2006 given in our clinic were reviewed. The date, drug name, dose, diagnosis, intention of therapy (curative, adjuvant, or palliative), and provider status (staff or fellow) were entered into an Excel spreadsheet. Package inserts for each drug were reviewed to determine if the medication was given on- or off-label. The dates of approval and label updates were further defined from FDA press releases. The percentage of courses and individual doses given off-label were calculated. Results: 186 patient charts were included in the analysis. Of 1,341 courses of chemotherapy, 50.48 % (n = 677) were given off-label. Of 3,299 doses of chemotherapy, 47.9% (1,581) were given off-label. Of the drugs prescribed, the most frequently dosed off-label were fluorouracil (n = 334), capecitabine (n = 229), traztuzumab (n = 123), leucovorin (n = 119), and carboplatin (n = 112). Of the 1,581 doses given off-label, 49% (n = 779) were given adjuvantly, 34% (n = 543) were given palliatively, and 16% (n = 259) were given curatively. Conclusions: Based on the current FDA labeling of chemotherapeutics, nearly half of the doses given in our outpatient clinic were off-label. However, the vast majority of our off-label use, such as adjuvant fluorouracil-based therapy, is considered standard of care and is supported by National Comprehensive Cancer Network practice guidelines and compendium listings. This retrospective analysis adds to the scant literature regarding off-label prescribing practices in oncology. No significant financial relationships to disclose.
Treatment-related deaths (TRD) in investigator-initiated cancer cooperative group trials: From the datasets of 44 studies (4,964 patients) by the Japan Clinical Oncology Group (JCOG)
Authors: Kanato K. , Nakamura K. , Saito I. , Takashima A. , Tomii Y. , Kaba H. , Shibata T. , Fukuda H. , Sato A. , Shimada Y. 
Published: August 2020

6632 Background: The proportion of Serious Adverse Events (SAE) including TRDs has a critical impact on choosing a new standard therapy as well as the efficacy of treatment in clinical trials. The proportion of TRD (%TRD) has been reported in a single clinical trial, but an overall % TRD in plural clinical trials has merely been evaluated so far. Methods: The JCOG trials which met both of the following criteria were included in this analysis: i) started after 1995 by 2008, ii) primary analysis was completed. In JCOG, attribution of all reported SAE are classified by Data and Safety Monitoring Committee into 5 categories (definite, probable, possible, unlikely, not related) according to causality to protocol treatment, and the death with causality judged as definite, probable, or possible is defined as TRD. The total number of any deaths and TRD were counted in all included trials and the incidences (%) of TRD were calculated. The association between %TRD and the following trial profiles was evaluated: arm (standard vs. testing), phase, modality and median survival time of each arm. Results: In total, 44 JCOG trials (67 arms) with 4,964 patients were included in the analysis. The number of all deaths and TRD were 2,974 and 60. Thus, the overall %TRD for all enrolled patients was 1.2% (95%CI, 0.9–1.6%), and %TRD among all deaths was 2.0% (95%CI, 1.5–2.6%). Major results of the association between %TRD and trial profiles are shown in the table. The later phase trials showed the lower %TRD, and the trials with shorter MST tended to have higher %TRD. Conclusions: When the trial is in earlier phase and includes more advanced disease, the trial should be planned and performed more carefully about minimization of patient risk. [Table: see text] No significant financial relationships to disclose.
Subcutaneous or intravenous administration of romiplostim in thrombocytopenic patients with myelodysplastic syndrome (MDS)
Authors: Sekeres M. , Kantarjian H. , Fenaux P. , Becker P. , Boruchov A. , Guerci-Bresler A. , Hu K. , Franklin J. , Berger D. 
Published: August 2020

7009 Background: Thrombocytopenia is common in patients (pts) with MDS, and treatment options are currently limited to platelet (plt) transfusions. Romiplostim is an Fc-peptide fusion protein (peptibody) that stimulates plt production by the same mechanism as thrombopoietin. Methods: This was a phase II, multicenter, single arm, open-label study. Eligibility criteria included IPSS low or intermediate-1 risk MDS and a mean baseline plt count ≤50x109/L. Safety and efficacy of romiplostim were evaluated in pts receiving 750μg romiplostim according to one of 3 schedules: weekly or biweekly subcutaneous injections (QWSC or Q2WSC), or biweekly intravenous injections (Q2WIV). Plt responses were measured per IWG 2006 criteria. Results: Of the 28 pts enrolled, 17 (61%) completed the study; 22 (79%) were male and the mean (±SD) baseline plt count was 29 (±10) x 109/L. The mean age was 71 years and 19 pts (68%) had received plt transfusions in the past year. Mean duration of exposure to romiplostim was 12 (±8) weeks. The most common adverse events (AEs) were fatigue and headache (both 18%). Five pts experienced serious AEs, and there were 2 cases of disease progression to AML: one pt in the QWSC cohort who received romiplostim for 4 weeks and one in the Q2WSC cohort who received romiplostim for 20 weeks. For pts who completed 8 weeks treatment, 15/23 (65%) achieved a plt response, defined by IWG 2006 criteria, and 14/23 (61%) did not require a plt transfusion during this period. The small number of pts limited the ability to compare administration schedules; minor differences were observed in plt responses and plt transfusions, and the incidence of AEs appeared similar among cohorts. Conclusions: IV and SC romiplostim appeared well-tolerated and effective in raising plt counts and avoiding plt transfusions in low and intermediate-1 risk MDS pts. The dose recommendation for future studies is 750μg, given QW or Q2W SC. [Table: see text] [Table: see text]
Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia (AML)
Authors: Santos F. P. , Qiao W. , Cortes J. E. , Jones D. , Ravandi F. , Verma D. , Kantarjian H. , Borthakur G. 
Published: August 2020

7015 Background: Mutations of the FLT3 gene (in special internal tandem duplication -ITD) are common in normal karyotype AML (NK-AML) and are associated with shorter relapse free and overall survival (OS). The frequency of FLT3 mutations is lower in other cytogenetic subgroups and the impact on outcome is unclear. Methods: The records of patients (pts) with newly diagnosed AML (from 2003 to 2007) were reviewed. Pts were divided among three cytogenetic subgroups: Good-risk (t(8;21), Inv(16)/t(16;16)) Intermediate-Risk (Diploid,-Y) and Poor Risk (-5,-7, 11q abnormalities). FLT3 ITD and tyrosine kinase domain (TKD) mutations were determined on baseline DNA samples by a PCR based method with 1% sensitivity. Since the frequencies of FLT3 mutations were lower in good- and poor-risk subgroups, ITD/TKD mutations were considered together in the analysis, while in the intermediate risk group they were analyzed separately. Survival curves stratified by FLT3 mutation were estimated by Kaplan Meier plots and compared by logrank test. A Cox model was fit for OS, and non-significant variables were eliminated in a step-down fashion with a p- value cut-off of p = .10. Results: A total of 481 pts were included (65 pts=good risk, 272 pts=intermediate risk and 144 pts= poor risk). Prevalence of FLT3 mutations is shown in the Table. No difference was found in median OS between FLT3-mutated and FLT3- wild type pts in the good risk group (not reached (NR) vs NR, P = 0.57) nor in the poor risk group (55 vs 24 weeks, P = 0.44). In intermediate risk, OS was worse in FLT3-ITD positive pts (33 vs 89 weeks, P < 0.0001) but not in FLT3-TKD positive pts (77 vs 70 weeks, P = 0.89). In the Cox model, FLT3 mutations were prognostic for OS only in intermediate risk pts with FLT3-ITD (HR 2.63, P < 0.0001). Conclusions: In our cohort of pts, FLT3 mutations did not have a prognostic impact in AML with good and poor risk karyotype. [Table: see text] No significant financial relationships to disclose.
Results of a phase I study of clofarabine (CLO) plus cyclophosphamide (CY) in adult patients (pts) with relapsed and/or refractory acute lymphoblastic leukemia (ALL)
Authors: Faderl S. , Thomas D. A. , Gandhi V. , Huang X. , Borthakur G. , O'Brien S. , Ravandi F. , Plunkett W. , Bretz J. L. , Kantarjian H. M. 
Published: August 2020

7020 Background: CLO is a second generation nucleoside analog with FDA approval for children with ALL relapse. Single agent CLO in adult ALL was less active so that combinations of CLO with other active agents are pursued. As CLO inhibits DNA repair following exposure to DNA damaging agents, we designed a phase I study of the combination of CLO with CY. Methods: Pts ≥ 21 years (yrs) with primary refractory or relapsed ALL, NYHA class < 3, and a cardiac ejection fraction ≥ 45% were eligible. The continual reassessment method (CRM) was used to determine the maximum tolerated dose (MTD) from 4 pre-defined dose levels. The starting dose level was CLO 40 mg/m2 i.v. daily x 3d and CY 200 mg/m2 i.v. q12h x 3d. For cohort 2, CY was 300 mg/m2 and cohorts 3 and 4 maintained these doses with the treatment duration extended to 4 and 5 days, respectively. Results: Thirty pts have been enrolled. Median age was 28 yrs (range 21–72). Twenty-one pts had pre-B ALL, 5 pts pre-T/T ALL, 1 pt mature B ALL, and 3 pts biphenotypic acute leukemias. Karyotype was diploid in 10 pts and 2 pts had Ph+ ALL. Median number of prior regimens was 2 (1–5). Seven (23%) pts were primary refractory. Among the remainder, preceding median remission duration was 8.6 mos (1–39 mos). Five pts were treated in cohort 1 and 25 in cohort 2. One (20%) pt in cohort 1 and 9 (36%) in cohort 2 experienced DLTs (≥ grade 3) including transaminase elevations, diarrhea, hyperbilirubinemia, and (1 pt each) elevation of creatinine/renal failure, lipase elevation, rash, nausea/vomiting. Evaluable for response were 28 pts: 3 CR (one pt in cohort 1) and 1 marrow CR (OR 14%). All pts had pre-B ALL. One pt had Ph+ ALL, and one was primary refractory to HCVAD. Three early deaths due to infectious complications occurred (all in cohort 2). Conclusions: The MTD for this combination is CLO 40 mg/m2 i.v. daily x 3d and CY 200 mg/m2 i.v. q12h x 3d. DLT are mainly GI-related. A phase II extension is ongoing and will focus on efficacy data. [Table: see text]
A randomized phase II study of sapacitabine, an oral nucleoside analogue, in elderly patients with AML previously untreated or in first relapse or previously treated MDS
Authors: Garcia-Manero G. , Luger S. , Venugopal P. , Maness L. , Wetzler M. , Coutre S. , Stock W. , Borthakur G. , Chiao J. , Kantarjian H. 
Published: August 2020

7021 Background: Sapacitabine is a novel nucleoside analogue with a unique ability to cause irreparable single-strand DNA breaks and induce G2 cell cycle arrest. It is orally administered and has demonstrated promising anti-leukemic activity against relapsed or refractory AML and MDS in a phase 1 trial. We are conducting a multi-center, open-label, randomized phase 2 study to evaluate 3 dosing regimens of this drug. Methods: Eligible patients must be ≥70 years with AML previously untreated or in first relapse or ≥60 years with MDS previously treated with hypomethylating agents. The planned sample size is 60 AML patients and 60 MDS patients. Patients are to be randomized 1:1:1 to receive one of the 3 dosing regimens. The primary efficacy endpoint is 1-year survival. Secondary efficacy endpoints include rate of CR, CRi, or hematological improvement (HI) and response durations. Results: As of December 2008, 60 AML and 13 MDS patients were enrolled and had ≥ 30 days of follow-up. Preliminary efficacy data were available for the AML stratum. Overall response rate is 31% (13% CR/CRp, 5% PR and 13% HI). Median time to CR/CRp is 3–4 cycles (range 1–7). Eight deaths of all causes occurred within 30 days of randomization and all were in the AML stratum (13%). One death was considered to be possibly related to sapacitabine. Common adverse events (all grades, regardless of causality) included fatigue, nausea, vomiting, diarrhea, constipation, anemia, leukopenia, febrile neutropenia, neutropenia, thrombocytopenia, dyspnea and peripheral edema, most of which were mild to moderate in intensity. Conclusions: These interim data suggest that sapacitabine is safe and active across all 3 dosing schedules. Updated data will be presented at the meeting. [Table: see text] No significant financial relationships to disclose.
Effect of antithymocyte globulins (ATG) as part of the myeloablative conditioning (MAC) regimen on the risk of severe graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) from matched-unrelated donors (MUD)
Authors: Mohty M. , Balere M. , Socie G. , Milpied N. , Ifrah N. , Harousseau J. L. , Michallet M. , Blaise D. , Esperou H. , Yakoub-Agha I. 
Published: August 2020

7025 Here, we report the results of a multicenter retrospective study analyzing the effect of ATG, incorporated within the MAC regimen for MUD-transplants in leukemic patients. The purpose of the study was to compare the incidence and severity of acute and chronic GVHD as well as overall outcome. 171 adult patients with acute leukemia and MDS, for whom detailed allelic HLA typing (4 digits) was available, were included. 81% of patients were transplanted from 10/10 allelic MUD, and 19% from a MUD with at least one allelic difference. 120 patients (70%) did not receive ATG (no-ATG group), while 51 patients received ATG (ATG group; thymoglobuline* in all cases) as part of the MAC regimen. Except for a significantly higher number of allelic differences between recipient and donor (33% vs. 13%; p = 0.002), the no-ATG and ATG groups were strictly comparable. With a median follow-up of 30.3 (range, 2.6–68.1) months, grade 0–1 and 2–4 acute GVHD occurred in 74 (46%) and 88 patients (54%) respectively, with grade 3–4 acute GVHD being significantly lower in the ATG group (18% vs. 32%; p = 0.04). Extensive chronic GVHD was significantly lower in the ATG group (5% vs. 33%; p = 0.001). Patients from the ATG group had a higher incidence of limited chronic GVHD (33% vs. 18%; p = 0.06). Moreover, infection-related mortality was comparable between both groups (23% vs. 27%, p = NS). Also, NRM was comparable between both groups (30% vs. 29%; p = NS). In multivariate analysis, an HLA allelic mismatch and the non-use of ATG were associated with an increased risk of grade 3–4 acute GVHD (RR = 2.80, 95% CI, 1.5–5.3, p = 0.001; and RR = 2.4, 95% CI, 1.1–5.0, p = 0.02 respectively). Similarly, multivariate analysis showed that the absence of use of ATG was the unique parameter associated with an increased risk of extensive chronic GVHD (RR = 6.9; 95% CI, 1.7–29.0, p = 0.008). Finally, LFS and OS at 2 years were not significantly different between the no-ATG and ATG group (48.8% vs. 41.3%, p = NS; and 53.6% vs. 54.3%, p = NS; respectively). These results suggest a global long-term beneficial effect of ATG when used as part of the MAC regimen prior to allo-SCT from MUD (especially in the HLA mismatch setting). No significant financial relationships to disclose.
Usefulness of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) in predicting outcomes for adolescents and young adults (AYAs) with hematologic malignancies (HM) undergoing allogeneic stem cell transplant (alloSCT)
Authors: Wood W. A. , Deal A. M. , Moore D. T. , Whitley J. , Sharf A. , Serody J. S. , Gabriel D. A. , Shea T. C. 
Published: August 2020

7034 Background: The HCT-CI was developed to help predict overall survival (OS) and non-relapse mortality (NRM) in pts undergoing alloSCT, a procedure with significant toxicity. AYAs with cancer (ages 16–40) have been identified by the NCI as a high-risk group, but it is not known whether the HCT-CI is a useful predictor of outcomes in this relatively healthy population. Methods: All pts ages 16–39 at the time of alloSCT from 1992–2008 were included. HCT-CI was retrospectively calculated for pts with complete data available. Univariable Cox regression models were used to examine the association between covariates and OS and NRM. Results: 62 evaluable pts included 38 males and 24 females. 50 (81%) were Caucasian, 9 (15%) African American, and 3 (5%) other. Diseases included AML (23), CML (14), ALL (14), and other (11). All comorbidities had a frequency of <5% in this population except for pulmonary dysfunction (69%), hepatic dysfunction (27%), infection (19%), and psychiatric disturbance (10%). When dichotomized into categories of 0–2 (32) and >3 (30), the HCT-CI was significantly associated with OS (p = 0.0006) and marginally with NRM (p = 0.07). Because pulmonary dysfunction appeared to be the most important contributor to the HCT-CI, the diffusing capacity adjusted for hemoglobin and alveolar volume (DLCO/VA adj) was examined independently. When dichotomized into categories of <80% and >80% of normal, the DLCO/VA adj alone was also significantly associated with OS (p = 0.008), but not with NRM (p = 0.2). Conclusions: AYAs with HM undergoing alloSCT have a limited number of comorbidities in the HCT-CI. Pulmonary dysfunction is most prevalent, and the DLCO/VA adj alone appears to be nearly as predictive for OS as the HCT-CI. The discrepancy between the predictiveness for OS and NRM may reflect pre-treatment or disease status of this population at the time of transplant. No significant financial relationships to disclose.