bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antidepressant adherence trajectory before cancer diagnosis and risk of antidepressant discontinuation after cancer diagnosis among middle-aged US adults.
Authors: Onasanya Oluwadamilola , dosReis Susan , Damachi Udim , Camelo Castillo Wendy 
Published: June 2023

e18890 Background: For middle-aged adults taking antidepressants before cancer diagnosis, concerns exist about drug-drug interactions between antidepressants and antineoplastics. Clinical guidelines recommend detailed assessment of the new cancer survivor's past history of antidepressant use before considering antidepressant discontinuation. We aimed to determine whether, in real-world settings, the risk of antidepressant discontinuation after cancer diagnosis is associated with survivors’ past antidepressant adherence trajectories. Methods: A retrospective cohort of 45 to 64-year old individuals with incident cancer diagnosis (index date) and ≥2 antidepressant fills in the 9 months before index date, IQVIA PharMetrics Plus for Academics claims, 2006-2020. Antidepressant adherence in the 9-month baseline was measured as monthly proportion of days covered (PDC) before tamoxifen initiation. Group-based trajectory modeling (GBTM) was used to identify clusters of survivors with distinct antidepressant adherence trajectories pre-index date i.e., we calculated polynomial functions of monthly PDCs and compared 2 to 6-group finite mixture models to determine which model best fit the data, based on the Bayesian Information Criterion, expert-adjudged parsimony and ≥10% of the sample in each trajectory group. Antidepressant discontinuation after cancer diagnosis was defined as a 45-day gap in antidepressant supply. Survivors were censored at first of either antidepressant discontinuation, loss of enrollment or 1 year post-index date. Cox regression compared the hazard of antidepressant discontinuation by trajectory group, adjusted for demographics, mental disorder and cancer type. Results: We identified 7,293 middle-aged cancer survivors with prior antidepressant use; females 72%, mean age (SD) 56 (7) years. GBTM identified 4 adherence trajectory groups (consistently high, steady increase, declining, and recent start); metastatic cancer being characteristic of the latter 3 groups relative to the consistently high group. Antidepressant discontinuation was lowest in the consistently high group (26% [mean months-to-discontinuation: 9]) and highest in the declining (68% [5]) and recent start (51% [6]) groups, p < .01. Hazard ratios [95% CI] of discontinuation were significantly higher in the declining (2.7 [2.3 – 3.2]), recent start (1.9 [1.7 – 2.0]) and steady increase (1.5 [1.4 – 1.6]) groups, relative to the consistently high group. Conclusions: Middle-aged cancer survivors with past trajectories of consistently high adherence to antidepressants experience lower risk of antidepressant discontinuation after cancer diagnosis in real-world practice. However, concern remains about the unintended health outcomes of relatively higher antidepressant discontinuation among survivors diagnosed with metastatic cancer.
Difference in persistence between tablets and capsules.
Authors: Zaidi Shehla , Rutter Cliff , Avalos-Reyes Elisea , Shah Dipti , McAuliff Kelly , Grover Rashmi , Feczko Lucia , Liu Chen , Kipping Emily , Johnson Kjel Andrew 
Published: June 2023

e18894 Background: More recently, pharmaceutical companies have developed capsule and tablet forms of their drugs to allow a choice on dosage form. As both capsules and tablets should be bioequivalent, adherence rates between members prescribed capsules and tablets should be the same. This study compares persistency between capsule and tablet forms of enzalutamide and palbociclib. Methods: This retrospective cohort study included adult Caremark members who received enzalutamide and palbociclib between 03/01/2021 and 03/01/2022 with continuous eligibility for six months prior and 12 months post-index into the study. Members were excluded if they had a > 60-day gap in fill or switched from a capsule to a tablet or vice versa during the study period. Adherence was measured using the prescription-based proportion of days covered (PDC) and defined as the sum of days with medication on hand divided by the number of days between index fill and exhaust of last fill. Continuous variables were compared with the student’s t-test and Mann-U tests; categorical variables were compared with a chi-square test. Logistic regression was utilized to assess adherence differences in capsules vs. tablets; p-values < 0.05 were significant. Results: 5,997 members were included in the enzalutamide cohort; there were no insurance type or region differences (all p > 0.05) between members receiving capsules and tablets. There were no significant differences in mean PDC (mean (SD) 0.963 (0.080) vs. 0.964 (0.073); p = 0.521) or adherence rates (94.2% vs. 95.2%); p = 0.215) between members receiving capsules and tablets. After adjusting for the variables in the model, there was no difference in adherence rates between tablets and capsules. Members less than 65 years of age had significantly lower adherence rates (odds ratio (OR)) 0.5 (95% confidence interval (CI), 0.35-0.71) compared to those aged 65-74. 5,361 members were included in the palbociclib cohort; there were significant differences in age, gender, type of insurance and region (all p < 0.05) between members receiving capsules and tablets. There were no significant differences in PDC (0.962 (0.072) vs. 0.960 (0.072); p = 0.534) or adherence rates (94.9% vs. 94.9%); p = 1.0) between members receiving capsules and tablets. Conclusions: In this study, capsule and tablet forms of enzalutamide and palbociclib had similar adherence rates when adjusting for confounders.
The impact of receipt of systemic anticancer therapy (SACT) near the end of life (EOL) on cost among oncology practices participating in CMS' Oncology Care Model (OCM).
Authors: Adelson Kerin B. , Canavan Maureen , Sheth Karna , Scott Jeffrey A. , Westvold Sarah 
Published: June 2023

e18923 Background: Chemotherapy administered near the EOL is associated with higher costs due to downstream care that occurs when patients do not transition to hospice, such as hospitalizations and ICU use. Since 2015 rates of systemic therapy at the EOL have remained stable, while chemotherapy has been replaced with costly immunotherapy. Recently, we showed receipt of immunotherapy at the EOL is also associated with higher rates of acute care use than among patients who don’t receive by SACT near the EOL. Using data from practices participating in OCM, we evaluated the relationship between receipt of chemotherapy, immunotherapy, or no systemic therapy at the EOL and categories of cost. Methods: We used anonymized Integra Connect data for OCM episode claims attributed to 8 multi-site OCM practices from July 2016-December 2021 to identify decedents capable of making treatment decisions. We stratified patients by SACT type received within 30 days of death (immunotherapy (IO), chemotherapy (CT), or none) and used t-tests to compare the mean episode costs. We evaluated differences in overall costs as well as those billed under Medicare subgroups: Part A, inpatient acute care use and other services including (hospice, SNF, HHA), Part B, infusion drug administered in the ambulatory setting and medical and ED costs, and Part D, oral pharmacy costs. Results: Among 14,169 OCM decedents overall mean cost within 30 days of death was $22,215. Overall cost within 30 days of death was higher for patients receiving some form of SACT (IO: $26,072 or CT: $23,259) compared with no SACT $19,296 (table) all p < 0.01). Patients who received no SACT at EOL had significantly lower Part B and D compared with both IO and CT respectively (all p < 0.01). Additionally, patients who received CT had lower average part B costs $8,081 compared with patients who received IO within 30 days of death $13,951 p < 0.01. Conclusions: Overall costs for patients who received IO or CT within 30 days of death were significantly higher than patients who received no SACT within 30 days of death. While IO patients had nearly twice as high mean Part B costs per episode compared with CT patients, CT patients had higher mean Part D costs per episode. Further research should explore whether these findings are generalizable to patients outside of OCM. [Table: see text]
Cost-effectiveness analysis of a circulating tumor DNA-based molecular residual disease assay to guide adjuvant chemotherapy decisions in patients with resectable early stage colorectal cancer.
Authors: Schneider John , Bresnahan Ryan , Chami Nadine , Brackstone Muriel , Hannouf Malek B. 
Published: June 2023

e18929 Background: An ongoing prospective study in patients with stage II or III colorectal cancer (CRC) has demonstrated ctDNA testing to be prognostic of recurrence risk and predictive of adjuvant chemotherapy (ACT) benefit. From the perspective of a US payer, we aimed to investigate the cost effectiveness of incorporating ctDNA analysis using the commercially available molecular residual disease (MRD) assay (Signatera™) into standard practice to aid in adjuvant chemotherapy decision-making, where traditional high-risk clinicopathological (CP) features have not shown a significant benefit of ACT in Stage II CRC. Methods: We developed a decision model to project lifetime clinical and economic consequences of different adjuvant treatment-guiding strategies. The model was parameterized using a follow-up of up to 2-years from a recently published data from GALAXY study and the cost data from the US literature. GALAXY is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analysed pre-surgical and post-surgical ctDNA in patients with stage II-IV resectable CRC. Costs are presented in 2023 US dollars. Future costs and benefits were discounted at 3%. Results: Compared to the CP predictors alone-based strategy, ctDNA analysis using the MRD assay in combination with CP predictors-based strategy led to an increase of 0.8 life years and 0.7 quality adjusted-Life Years (QALY) and cost savings of $9,771 per patient. Conclusions: The addition of MRD detection by ctDNA to traditional CP predictors aids in adjuvant chemotherapy decision-making in patients with stage II or III resectable CRC and is likely to be cost effective in the US healthcare system. ctDNA testing should therefore be considered for adoption in this disease setting.
Outcomes of myeloid malignancies in patients previously treated with PARP inhibitors for solid malignancies: A single institution experience.
Authors: Almanza-Huante Emmanuel , Bataller Alex , Urrutia Samuel , Gener-Ricos Georgina , Briski Robert , Kanagal-Shamanna Rashmi , Lu Karen H. , Westin Shannon Neville , Yap Timothy A. , Takahashi Koichi , Ravandi Farhad , Alvarado Valero Yesid , Kadia Tapan M. , Sasaki Koji , Kantarjian Hagop M. , Garcia-Manero Guillermo 
Published: June 2023

e19000 Background: Treatment with Poly(ADP-ribose) Polymerase proteins (PARP) has improved the survival of patients (pts) with solid malignancies harboring a homologous recombination deficiency (HRD). The association between PARP inhibitors (PARPi) and the development of myeloid neoplasms post cytotoxic therapy (MN-pCT) has been reported. We aim to describe the characteristics and outcomes of pts who develop MN-pCT after treatment with PARPi. Methods: Pts treated with PARPi at a single institution from July 2014 to August 2022, who developed MN-pCT (AML, MDS or CMML), were retrospectively evaluated. Diagnosis of MN-pCT was defined according to the 5th edition of the WHO criteria. Clinical and demographic characteristics along with cytogenetics and molecular features were analyzed. HRD was assessed by NGS on peripheral blood with a 13-gene panel. Results: 1462 pts were treated with PARPi at MDACC. Of these, 15 (1%) developed MN-pCT. These include 9 (60%) with MDS, 5 (34%) with AML, and 1 (7%) with B/Myeloid Mixed-Phenotype Acute Leukemia (MPAL). The median age was 62 (46-74) years and 14 (93%) were female. The most frequently used PARPi was olaparib in 9 (60%) pts. All pts had also previously received platinum-based agents and taxanes. Pts with 19 different solid tumors were included; 11 (85%) had active concomitant solid tumors at the time of MN-pCT. The median time from PARPi treatment to myeloid neoplasm (TTM) was 20.7 months (9.3-39.9). Cytogenetics and molecular features were available in 14 pts (93%). Eight (57%) had complex karyotype. The median number of mutations were 2 (0-4). TP53mut was present in 9 (64%) pts with a median VAF 47.3% (11.9-76.6%) of whom 6 (67%) were biallelic. The ORR to antileukemic therapy was 66% (n = 8): 3 (38%) had CR, 2 (25%) had PR, 2 (25%) had mCR with HI and 1 (13%) had isolated HI. The patient with B/myeloid MPAL was not evaluable for response. Of the responders, 7 (88%) pts relapsed at a median of 2.8 months (1.5-4.2). The median OS and EFS on the whole cohort were 7.8 (3.2-12.4) and 5.3 (3.8-6.7) months respectively. Conclusions: Development of MN-pCT in pts treated with PARPi is rare but most outcomes are very poor. Prospective analysis to evaluate pts at higher risk of developing MN-pCT is warranted in order to select pts who might benefit from novel therapies without increasing the risk of secondary myeloid malignancies. [Table: see text]
Association of FLT3 and NPM1 mutations in patients with acute myeloid leukemia with metabolomic patterns determined by mass spectrometry.
Authors: Toprak Selami Kocak , Gerekci Yesilyurt Selin , Koyun Derya , Ozcan Muhit , Özen Can 
Published: June 2023

e19003 Background: Patients diagnosed with Acute Myeloid Leukemia (AML) are categorized into risk groups based on cytogenetic and molecular abnormality tests, which determine the specific treatment regimes. Since mutation tests take time and some emergency patients require immediate treatment, a method to provide fast clinical data that will be the basis for initial treatment regime is needed. Aim of the study is to discover patterns associated with FLT3 and NPM1 mutations in AML patients, which will provide a fast clinical information to clinicians. The hypothesis is based on the previous studies which indicate a link between NPM1 and FLT3 mutations with metabolism. The mutations were chosen based on their high frequency in AML patients and their critical role in risk group determination. Methods: All AML patients (n = 42) and healthy individual samples (n = 16) were obtained from Ankara University Hematology Department. Patient groups were divided into five groups based on the mutation status. Pattern determination of the mutations was achieved by LC-MS/MS measurements of amino acid and acyl carnitine panels that are highly associated with metabolism. After preprocessing of the raw data, univariate (ANOVA) and multivariate analyses (PCA and PLS-DA) were performed to define class discrimination between sample groups. The remarkable analytes that have significant power in the discrimination were determined by VIP analysis. The developed model was validated with K-Fold cross validation method and permutation test. The most significant pathways in class discrimination were identified with pathway analysis. Visualization was accomplished via Metaboanalyst 5.0 software. Results: Principal Component Analysis (PCA) showed that 79% of the total variance of the sample groups was explained by the model. In order to increase class discrimination, Partial Least Squares-Discriminant Analysis (PLS-DA) was performed. R2Y and Q2 were found as 0.845 and 0.619, respectively. PLS-DA model was validated with K-fold analysis and permutation test. In all the validation experiments, a low cross-validation error was observed. In VIP analysis, the most significant analytes that cause the class discrimination were found as C0 carnitine, glutamic acid, aspartic acid, respectively. In the pathway enrichment analysis performed with these analytes, aminoacyl t-RNA biosynthesis, arginine biosynthesis, valine-leucine-isoleucine biosynthesis were found as statistically significant pathways responsible for the class discrimination. Conclusions: A preliminary model based on the targeted metabolomics approach was developed for the prediction of mutation status of NPM1 and FLT3 proteins in AML patients. Proposed model has a high fit value, validity, and strong predictive power. The reliability and validity of the model can be further increased by future multicenter studies.
Molecular and cytogenetics abnormalities in acute myeloid leukemia at Puerto Rico.
Authors: Marrero-León William Doel , Cintron-Colon Hector R. , Cruz-Rodriguez Steven , Caceres William , Rodriguez-Arocho Cristian I. , Cruz Alexis 
Published: June 2023

e19005 Background: Acute myeloid leukemia (AML) is a highly heterogeneous disease. Specific cytogenetic and molecular features permit stratification of this disease. Prognosis within these categories varies widely. Determining optimal management has been complicated by the multiple molecular disease subsets with different responses to standard therapeutics. The comprehensive genetic analysis of AML in the past 10 years has revealed recurrent, somatically mutated genes, leading to the development of new targeted therapies including inhibitors of FLT3 and IDH. Decisions about the choice of therapy in patients with AML currently depend on the identification of a selected set of genetic markers at diagnosis. At Puerto Rico, AML data of cytogenetic and molecular markers is lacking. According to the Puerto Rico Cancer Registry from 2015 to 2019 a total of 551 cases of AML were reported. The San Juan City Hospital-hematology oncology department is one of the major referral centers on the island for initial evaluation and management of AML. The objective of our retrospective study was to identify the most common cytogenetic and molecular abnormalities present in our population. Patient conditions were stratified as favorable, intermediate, or high risk, in terms of prognosis using the ELN revised 2022 stratification. Methods: This study examined the frequency of molecular markers in newly diagnosed (ND) patients with AML. We evaluated patients that were at least 18 years of age or older with cytogenetic and molecular analysis in a period of 4 years (2019-2022). All data regarding demographic, bone marrow biopsy, cytogenetics, and molecular markers were obtained from electronic medical record at our institution with institutional review board approval. Results: A total of 140 patients with ND AML were identified during the study period. 58% female and 42% male with a median age of 57 years old at time of diagnosis. In terms of molecular markers, the most common were RUNX1 (22%), follow by IDH2 (14%), FLT3-ITD (14%) and TP53 (11%). Complex cytogenetics was identified in 40% patients, and 34% had Myelodysplasia related cytogenetic. Using the ELN 2022 criteria to classify AML patients in terms of risk with cytogenetics and molecular markers, our study revealed 21% favorable risk, 31% intermediate, and 48% adverse. Conclusions: Our study suggests that our population has higher prevalence of AML with myelodysplasia-related gene mutations and molecular related to adverse risks, such as RUNX1. Further studies with appropriate sub-group analysis need to be followed to determine if there is any genetical predisposition on the puertorrican population for myelodysplasia related genes or for RUNX1.
Inotuzumab ozogamicin (INO) for the treatment of measurable residual disease (MRD) in patients with B-cell acute lymphoblastic leukemia (B-ALL): Results from a phase II study.
Authors: Nasr Lewis Fady , Short Nicholas James , Senapati Jayastu , Alvarado Valero Yesid , Jain Nitin , Konopleva Marina , Macaron Walid , Ravandi Farhad , Dinardo Courtney Denton , Sasaki Koji , Ferrajoli Alessandra , Nasnas Cedric Christophe , Zoghbi Marianne , Jacob Jovitta , Mayor Ejiroghene , Milton Anna , Loiselle Christopher , Garris Rebecca , Kantarjian Hagop M. , Jabbour Elias 
Published: June 2023

e19008 Background: INO is effective in relapsed/refractory B-ALL and may have utility in eradicating MRD in patients (pts) in MRD-positive (MRD+ve) remission. Methods: This is a phase II trial of pts with B-ALL in complete remission (CR) with persistent MRD+ve or with MRD+ve relapse. Eligible pts were required to be MRD+ve at ≥0.01%. MRD negativity (MRD-ve) was defined as undetectable MRD by flow cytometry (sensitivity 10-4) for Philadelphia (Ph)-negative (Ph-) B-ALL and undetectable MRD by both flow and PCR for BCR:ABL1 for Ph-positive (Ph+) B-ALL. INO was given at a dose of 0.6 mg/m2 on D1 and 0.3 mg/m2 on D8 of cycle 1 and 0.3 mg/m2 on D1 and 8 of subsequent cycles (up to 6 total cycles, given every 21-28 days) along with ursodiol prophylaxis. Pts with Ph+ ALL received concomitant TKI. Results: 27 pts with MRD+ve B-ALL were treated between 11/2018 and 6/2022 (Table). 17 pts (63%) had Ph+ B-ALL (15 received ponatinib and 2 dasatinib), and 10 pts had Ph- B-ALL. 20 pts (74%) were in CR1, and 7 pts (26%) were in CR2 or beyond. 14 pts (52%) had received prior blinatumomab and 5 pts (18%) had prior stem cell transplantation (SCT). 18 pts (67%) became MRD-ve (responders), 16 after the 1st cycle and 2 after the 2nd cycle of INO. In the Ph+ group, 10/17 pts (59%) responded; another 3 pts achieved major molecular response. 8/10 (80%) pts with Ph- B-ALL responded. The median number of cycles of INO were 3 (range, 1-6). Rates of MRD response were higher in pts without prior blinatumomab (11/13 pts [80%]), compared with those with prior blinatumomab exposure (7/14 [50%]) ( P=0.06). After a median follow-up of 21 months, 13/18 responding pts (72%) are in ongoing MRD-ve CR. Among the 18 responders, 6 pts underwent allogeneic stem cell transplant (ASCT) after a median of 3 cycles of INO (range, 1-4); all were in MRD-ve CR at the time of ASCT. 4/18 responders (22%) relapsed, 1 of whom relapsed after ASCT. Median RFS and OS for the whole group were not reached; estimated 2-year RFS and OS were 61% and 62%, respectively. 2-year OS for responders and non-responders were 76% and 50% (P=0.34), respectively. 2-year RFS for pts with or without prior blinatumomab was 23% and 91%, respectively; P=0.04. No grade 4 non-hematological toxicities were observed. 1 pt (who had a history of prior ASCT) had grade 3 sinusoidal obstruction syndrome. Conclusions: Low-dose, fractionated INO is effective at eradicating MRD in pts with B-ALL and can result in durable MRD-ve remissions. Clinical trial information: NCT03441061 . [Table: see text]