bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of prospective review of medical oncology treatment plans (TPs) on quality of care, payer denial, and cost.
Authors: Flood William A. , Yedwab Erik , Alley Evan W. , Gilman Paul , Frick Kevin D. , Forastiere Arlene A. 
Published: March 2020

e17565 Background: Retrospective review of chemotherapy TPs for compliance with expected care presents financial and quality risks to providers, patients and payers. Prospective assessment of TPs before oncology care is delivered may limit these risks. Methods: Through the eviti web-based decision support platform, oncologists/staff submit TPs for review. The eviti Evidence-Based Library incorporates all recognized guidelines (ASCO, NCI, ASTRO, NCCN and others), the supporting literature and NCI registered clinical trials. Evidence-based treatments are approved while unexpected variances are not reported to the payer until medical record review and peer to peer (P2P) discussion when records are insufficient. The eviti data base was queried for all off-study treatment plans submitted by medical oncology providers in a single state from January 2011 through October 2012. The nature of variation, results of P2P discussion and final recommendation to the payer were then determined. Net cost differences between the proposed and expected care were calculated using ASP+6% in November 2012. Results: Of a total of 202 TPs submitted on 116 individual patients, 89 TPs (44%) included 92 unexpected variations of care at initial submission, 11 of which (12%) presented safety issues documented in the peer reviewed literature and guidelines. The total net cost difference for one cycle of the proposed care and expected standard was $304,055. Of these 92 unexpected variations, only 29 (32%) of the variations could not be unjustified and referred for probable denial by the payer. After review of medical records, 21 (23%) were referred to the payer as medical justified variations (MJV), while after P2P 17 (18%) were considered MJV’s and 25 (27%) were modified to fit expected patterns of care. Additional analysis by drug classes and cost will be presented. Conclusions: In this TPs set, prospective review of treatment plans decreased the incidence of non-EBM care, the rate of potential denials, and the cost of care. Prospective TPs review can limit risk to all parties in cancer care.
A national survey on patients’ enrollment rate in oncology clinical trials: The French experience.
Authors: Pauporte Iris , Thibaudeau Valerie , Calvo Fabien M. , Buzyn Agnes 
Published: March 2020

e17567 Background: The rate of patients enrolled in clinical trials (CT) is one of the main indicators of clinical research and care activity. The successive French Cancer Plans (2003-2007 and 2009-2013) aimed at quantifiable targets of patients to be enrolled in high-quality clinical trials. To help investigators achieving this objective, a substantial financial support for clinical research associates (CRA) recruitment was given to University Hospitals (UH), Comprehensive Cancer Centers (CCC) and public or private community hospitals (CH). In the meantime, significant public investment was allocated to competitively selected academic projects through the Clinical Research National Program. Methods: From 2006 to 2011, we carried out annual national surveys on clinical research activities in oncology in France. A questionnaire was sent to cancer care institutions. Number of CT open for enrolment, number of CT sponsored by the institution, number of patients enrolled and human resources (CRA) were collected. Academic and industry-sponsored trials were analyzed separately. Results: We showed that the number of patients enrolled in CT increased continuously over this period: from 21,500 in 2002 to 35,400 in 2011 (+47%). Based on these figures and assuming that there were 420,000 to 472,000 patients eligible for CT over this period, the enrolment rate for patients in CT is estimated to be 7.5 to 8.5% in 2011 versus 5.8 to 6.7% in 2003. Nearly 80% of all enrolled patients were recruited in academic CT; over 75% of patients in therapeutic trials. UH and CCC equally contributed for 80% of enrolment, CH for the residual 20%. At last, the number of CT increased by more than 35% over the same period, while the number of CRA was multiplied by 3 over the French territory. Conclusions: Our results show that public intervention for improving enrolment to cancer CT seems to be efficient. Other types of intervention are being considered, i.e., targeted on investigators, on patients, or on both. Future work should also consider the impact of CT enrolment on patients’ outcome.
Efficacy and safety of balugrastim in chemotherapy-induced neutropenia: Integrated analysis of two randomized phase III studies.
Authors: Gladkov Oleg , Volovat Constantin D. , Barash Steven , Buchner Anton , Avisar Noa , Bias Peter , Mueller Udo W. 
Published: March 2020

e17572 Background: Balugrastim is a recombinant fusion protein composed of human serum albumin and human granulocyte colony-stimulating factor, which allows for once-per-chemotherapy cycle administration. We present a combined analysis of two double-blind, randomized Phase III studies comparing efficacy and safety of balugrastim vs pegfilgrastim in breast cancer patients receiving myelosuppressive chemotherapy (CTx). Methods: All patients were treated with doxorubicin 60 mg/m2 followed by docetaxel 75 mg/m2 administered by i.v. infusion on Day 1 of a 21-day cycle for up to 4 cycles. For each cycle, patients received a single s.c. injection of balugrastim approximately 24 hours after administration of CTx. The primary endpoint for both studies was duration of severe neutropenia (DSN) in Cycle 1. Safety of balugrastim was assessed by evaluating the type, frequency, and severity of adverse events (AEs); changes in laboratory parameters and vital signs, and immunogenicity over time. Analyses were performed in the per-protocol population. Results: A total of 469 patients were randomized to receive balugrastim 40 mg (N=235) or pegfilgrastim 6 mg (N=234). Mean DSN in Cycle 1 was 1.1±1.11 days in patients receiving balugrastim (n=236) and 1.0±1.14 days in patients receiving pegfilgrastim (n=234). Non-inferiority was demonstrated by statistical analysis for balugrastim vs pegfilgrastim for reduction in DSN across studies. Patients treated with balugrastim had a significantly shorter time to ANC recovery in Cycle 1 vs pegfilgrastim (2.0 vs 2.3 days; P=0.015). No other significant differences were seen between treatment groups in either study for any other secondary endpoints in Cycles 1–4. The safety profile was similar for both drugs, with the incidence of AEs consistent with the underlying medical condition and administration of myelosuppressive CTx. Conclusions: In both Phase III studies, non-inferiority was clearly demonstrated for balugrastim 40 mg vs pegfilgrastim 6 mg. Balugrastim is a safe and effective alternative to long-acting pegfilgrastim for reducing DSN in breast cancer patients receiving myelosuppressive chemotherapy. Clinical trial information: 2010-019001-42.
Dosing of chemotherapy for solid tumors based on ideal body weight versus actual body weight: Review of a military oncology clinic’s practice.
Authors: Miller Lonnie D. , Henderson Aaron , Vietor Nicole , George Benjamin Jacob 
Published: March 2020

e17575 Background: Dose-reductions or “capping” of the body surface area (BSA) at 2.0m2 for chemotherapy due to obesity has been widely practiced throughout oncology due to the concerns about AE in obese patients. In 2012 ASCO published guidelines recommending that full weight-based dosing of chemotherapy be used. This retrospective review was undertaken to evaluate the dosing practices at a major U.S. Army oncology clinic. Methods: Retrospective, random sampling of patients with breast, lung, gastrointestinal and testicular cancer and lymphoma treated at a tertiary military medical center within the last three years. Basic demographic data, cancer type, stage, actual and ideal BSA , incidence of dose-reduction, hematologic data before and after cycle 1, incidence of grade 3-4 toxicity and use of granulocyte-colony stimulating factor was recorded. Results: 231 patients (61.9% female, 38.1% male) were included in the analysis (breast 36.4%, lung 19.5%, GI 21.2%, testicular 6.5%, lymphoma 16.5%). The majority of patients were white, 70.6%, with asian, black, hispanic and other making up 2.6%, 13.4%, 1.7% and 11.7% respectively. Seventy-eight had a BSA >2.0m2. No incidences of dose-reduction were identified. Analysis did not show a correlation between differences in actual vs. ideal BSA and toxicity. When other variables were considered, there was a statistically significant inverse relationship between age and grade 3-4 toxicity (p=0.02) although this was deemed clinically insignificant (coefficient of determination <0.25). Conclusions: In a retrospective review of chemotherapy dosing practices in a major military medical center, we found no cases of dose-reduction based on obesity. There was also no significant increased toxicity when patients were dosed according to actual vs ideal body weight in keeping with previously published literature. There was a significant inverse relationship between age and grade 3-4 hematologic toxicity.
Effect of availability of oral iron chelation therapy (ICT) on initiation, duration, and dose adequacy in patients with myelodysplastic syndromes (MDS) and transfusional iron overload (TIO).
Authors: Gore Steven , Davidoff Amy J. , Hendrick Franklin , Duong Vu , Stuart Bruce C. , Baer Maria R. , Shenolikar Rahul , Zeidan Amer 
Published: March 2020

e17584 Background: Most patients with MDS do not receive ICT despite evidence of TIO. Till 2005, the only approved ICT was Deferoxamine (DFO), a drug which requires daily prolonged parenteral administration. In addition to therapeutic equipoise of its efficacy, the logistics of administration of DFO may limit ICT use in MDS. We sought to assess whether the approval of an oral ICT (Deferasirox, DFX) in November 2005 has changed ICT use rates, dose adequacy and adherence in MDS patients with TIO. Methods: Using 100% Medicare enrollment and claims data from 2005-2008, we selected beneficiaries with MDS who were enrolled in Medicare Parts A, B, and D and were ICT-eligible based on RBC transfusions ≥ 20 units. Cox proportional hazard models examined the effect of time period relative to DFX market entry on the probability of ICT initiation and the effect of DFX vs. DFO use on duration and dose adequacy. Results: Of 3,843 ICT-eligible patients, 13.8% received ICT, with 81.6% of those receiving DFX, and 29.5% receiving DFO. Relative to the latter half of 2005, the probability of ICT initiation increased beginning in 2007, with a hazard ratio of 1.793 (CI,1.13-2.84; P=0.012) associated with cohort entry in the latter half of 2008. Treatment duration was longer for beneficiaries using DFX (mean 29.7, median 22 weeks) compared to DFO (mean 19.43, median 9 weeks). Only 7.1% of DFO-users received an adequate dose, compared to 72.8% of DFX-users. Conclusions: Use of oral ICT (DFX), following its approval, was associated with increased use, duration and dose adequacy of ICT, compared to DFO, among Medicare beneficiaries with MDS and TIO. The dramatic increase in use associated with availability of an oral formulation may have implications for other new oral chemotherapy and supportive care drugs.
Awareness of HPV and its vaccine among lesbian, gay, bisexual, transgender, and queer (LGBTQ) populations.
Authors: Ong Caroline , Winer Joel , Margolies Liz , Dai Feng , Patridge Eric , Chagpar Anees B. 
Published: March 2020

e17597 Background: HPV is a sexually transmitted virus that is known to cause of a number of malignancies, including anorectal and oral cancers. However, there is a paucity of data regarding the knowledge of HPV and its now FDA-approved vaccine amongst LGBTQ populations. We sought to compare awareness of HPV and the vaccine in an LGBTQ sample to the general population. Methods: An anonymous electronic survey was conducted through well-known LGBTQ organizations. The survey was designed to replicate verbatim questions regarding HPV fielded in the 2010 National Health Interview Survey (NHIS) Cancer Supplement. Data from the LGBTQ survey was compared to the nationally representative population surveyed in the NHIS. Results: A total of 323 LGBTQ people responded to the survey; 148 were female (90 lesbian, 25 bisexual, and 33 queer/other), 158 were male (141 gay, 5 bisexual and 12 queer/other), 13 were transgender and 4 identified themselves as other/queer in gender. The median age of the cohort was 34.4 (range; 16-74). Of this population, 297 (92.0%) had heard about HPV (vs. 61.5% in the general population in NHIS). Both LGBQ men and women were equally likely to have heard about HPV (92.4% and 91.3%, respectively), whereas knowledge regarding HPV was more disparate between men and women in the general population (47.2% and 75.6%, respectively). Of the 11 transgender people who responded to the questions regarding HPV, all had heard about the virus. 88.5% of the LGBTQ cohort had heard about the vaccine; compared to 51.3% in the general population in NHIS. Again, there was less of a gap in knowledge between men and women in the LGBQ community (90.6% and 87.3%, respectively) than there was in the general population (68.1% and 34.0%, respectively). 10 of the 11 transgendered people who responded to questions regarding HPV (90.9%) were aware of the HPV vaccine. Conclusions: The LGBTQ community appears well-educated regarding HPV and its vaccine, compared to the general population. These findings are gratifying given the potential increase in risk of HPV-related malignancies in these populations, but further work is needed to explore whether this increased awareness translates into increased HPV-vaccination rates.
Efficacy of the hypomethylating agents as frontline, salvage, or maintenance therapy among older adults with acute myeloid leukemia (AML).
Authors: Tawfik Bernard , Sliesoraitis Sarunas , Klepin Heidi D. , Lawrence Julia , Isom Scott , Ellis Leslie R. , Lyerly Susan , Manuel Megan , Dralle Sarah , Berenzon Dmitriy P. , Powell Bayard L. , Pardee Timothy S. 
Published: March 2020

e18002 Background: The hypomethylating agents, azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with AML. Little is known about how AML responds to hypomethylating agents after standard therapy and the use of these agents in the treatment of AML is currently evolving. Methods: We retrospectively examined 76 consecutive AML patients ≥60 years old treated with hypomethylating agents at Wake Forest from 2002-2009 as either 1st-line therapy (n=35), salvage (n=28) or consolidation (n=13). We collected data on age, gender, race, Charleston Comorbidity index (CCI), cytogenetics, type of treatment, Complete Remission (CR), Complete Remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan-Meier estimates and cox proportional hazards models. Results: In the front line setting 11.4% of patients received azacitidine (AZA), 34.3% received 5 days of decitabine (5DD) and 54.3% received 10 days (10DD). In the salvage cohort 3.6% received AZA, 42.8% received 5DD and 53.6% received 10DD. In the consolidation cohort 18.2% received AZA and 81.8% received 5DD. Response rates (CR+CRi) were reduced in the salvage cohort compared to frontline (3.6% versus 25.7%, p=0.033). Despite the reduced response rate, overall survival in the two cohorts was similar when survival was calculated from time of hypomethylating agent (8.2 [CI 4.8-10.3] vs. 3.1 [CI 1.9-12.0] months, p = 0.2967). In the salvage cohort overall survival from the time of relapse was similar to the overall survival of those treated in 1st consolidation (18.3 [CI 15.1 -23.5] vs. 13.7 [CI 8.0 – 21.6] months, p= 0.3346). This suggests that hypomethylating agents given in first remission did not improve survival over patients who received them only after relapse. Comorbidity burden (by the CCI) showed a non-significant trend with prognosis (p= 0.0667). Conclusions: These data suggest prior cytotoxic therapy decreases marrow response rates to hypomethylating agents but not survival. Furthermore, use of hypomethylating agents for consolidation did not result in an increase in median overall survival when compared to their use in salvage.
Imatinib dose hike in suboptimal response and failure in CML CP: Results from a developing nation.
Authors: Gullipalli Muralidhar , Linga Vijay Gandhi , Kota Rajesh , Kalpathi Krishnamani , Maddi Rahul Narayan , Goteke Vamshi Krishna Reddy , Arigela Ravi Sankar , Nasaka Srividya , Ganta Ranga Raman , Gundeti Sadashivudu , Digumarti Raghunadharao 
Published: March 2020

e18003 Background: As perEuropean Leukemia Net (ELN) guidelines Imatinib 400mg/day is the standard of care in CML-CP. Options for patients with suboptimal response and failure are dose hike or change to second line TKIs. In resource poor countries where second line TKIs are expensive, dose hike of Imatinib may be an alternative. Methods: We retrospectively analyzed all CML - CP patients requiring dose hike at our centre from 2003-2009. Mutational analysis could not be performed. The trigger for dose hike to 600mg was suboptimal response or failure as per ELN 2010 guidelines. Event free survival (EFS), transformation free survival (TFS), and overall survival (OS) were analysed. EFS was defined as time from dose escalation to transformation to BC/AP or lost to follow up or death due to any cause. OS was defined as time from dose escalation to death. TFS was defined as progression to BC/AP from dose hike. Cytogenetic response was evaluated. Statistical analysis is done using Graphpad Prism. Results: There were 76 patients with a median age of 35 years (range, 13-68) and M: F ratio of 1.8:1.Trigger for dose hike was failure in 56 patients (73%) and suboptimal response in 27%. In failure group, after dose hike, complete cytogenetic response (CCR) was achieved in 41/56 (73%), partial (PCR) 4/56(7%), minor 5/56(9%), nil cytogenetic response in 6/56(10%). In suboptimal group CCR were seen in15/20(75%). Five year EFS, TFS and OS in both the groups together were 64.3%, 91.9%, and 94.7% respectively. The five year EFS, TFS and OS in failure group were 63.4%, 93.3% and 95.1% respectively. Five year EFS, TFS and OS in suboptimal group were 62.8%, 88.5% and 94.4% respectively. There was no significant difference between suboptimal and failure groups (p values for EFS-0.8414, TFS- 0.446,OS-0.7368). 75% patients experienced manageble toxicities. Conclusions: Dose hike to 600mg is still one of the viable options in CML CP patients with suboptimal response or failure in resource limited countries with an acceptable toxicity profile.
The outcome of acute biphenotypic leukemias in childhood: A single center experience.
Authors: Zulfikar O. Bulent , Cakir Betul , Koc Basak 
Published: March 2020

e18006 Background: Acute biphenotypic leukemias is a rare type of leukemia in childhood, expressing both myeloid and lymphoid markers. We evaluated 22 patients having biphenotype leukemia to document the characteristics and outcome. Methods: We reviewed the files of the children with acute leukemia referred to Istanbul University Oncology Institute between May 2000 – May 2011. Results: There were 21 (22%) patients, 11 girls and 10 boys, having biphenotypic features among 93 acute leukemia patients. Of these, 15 were B-lymhoid/myeloid, 6 were T-lymphoid/myeloid patients. Genetic analysis was performed in 18 patients. Two had t(12;21) positivity; philadelphia chromosome or myeloid translocations including 16 inv., t(8;21), t(15;17) were negative. Median follow up time was 65 months (21-109). All the patients were treated with COG high risk acute lymphoblastic leukemia protocols and achieved remission except 2 patients who required myeloid induction treatment (MRC 10 Protocol). Two of the patients relapsed at 30th and 34th months of follow-up. Conclusions: In our series, all the patients are in remission including two relapsed patients who are disease free with stem cell transplantation. The outcome of biphenotypic leukemia patients treated with lymphoblastic leukemia protocols were not lower than acute lymphoblastic leukemia patients. These patients need special care and prompt approach due to their problems during treatment.
Combination HDACi and mTOR inhibitor therapy in poor-risk de novo and refractory elderly patients with AML.
Authors: Sandilya Vijay Krishna , Ghai Vikas , Sharma Kamal , Abbi Kamal Kant Singh , Epner Elliot E 
Published: March 2020

e18012 Background: Valproic acid (VPA, 2-propylpentanoic acid) is a histone deacetylase inhibitors (HDACi), which has in vitro activity against Acute Myeloid Leukemia (AML) blasts. HDACi produce epigenetic modifications, and may have antineoplastic effects in AML by activating transcriptional silenced genes. The mammalian target of rapamycin (mTOR) pathways constitutive activation has been involved in the pathogenesis of various cancers, including AML. We present a series of two cases of poor risk de novo and refractory elderly AML patients treated with a combination of HDACi VPA and mTOR inhibitor sirolimus (S). Methods: This is a retrospective chart review garnered data on two patients with de novo AML and refractory AML who were treated with a combination therapy of VPA 500 mg three times a day with sirolimus 1 mg by mouth daily. Patients continued to receive treatment until disease progression. Results: Patient 1 achieved transfusion independence and a 6 month CR with ECOG PS 1 without hospitalizations. Repeat BM demonstrated no morphologic or immunophenotypic evidence of AML. Persistent disease was still detectable by FISH. Patient 2 was started on the regimen after persistent disease was detected by day 14 bone marrow, post standard 7 + 3 induction. Repeat bone marrow after 23 days of treatment with VPA and Sirolimus showed no immunophenotypic, morphological or cytogenetic evidence of AML. The patient remained in remission for 9 months on therapy with normal blood counts. Conclusions: We postulate that the use of VPA with sirolimus, is an active combination therapy for elderly, poor risk AML patients who may not otherwise tolerate intensive chemotherapy. The mechanism of action may involve activation of the mTORC2 pathway by HDAC1. Given our observations, further studies are warranted to better define the activity of this or similar combination therapies in elderly AML patients. [Table: see text]