bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of first-line pembrolizumab treatment in individuals with advanced non-small cell lung cancer and poor performance status.
Authors: Veluswamy Rajwanth , Ji Jiayi , Hu Liangyuan , Wang Xiaoliang , Smith Cardinale B. , Kale Minal 
Published: June 2021

e18796 Background: There is limited evidence supporting the optimal use of immune checkpoint inhibitors (ICIs) in NSCLC patients with poor performance status (PS), as clinical trials exclude these patients. In this study, we use real-world oncology data to determine the impact of first line pembrolizumab vs. no treatment in high PD(L)-1 expressing cancers in individuals with advanced NSCLC and ECOG PS ≥2. Methods: We performed a retrospective cohort study of patients with advanced NSCLC with ECOG PS ≥2 between 09/01/2014 and 02/18/2020, using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Patients were included if they were PD(L)-1 high (≥50%) and had clinical and treatment information recorded within 90 days of diagnosis. Real-world overall survival (rwOS) was defined as time from diagnosis to death (censored at last EHR activity). Median rwOS was estimated using weighted Kaplan-Meier methods. A marginal Cox structural model with inverse probability of treatment weighting was used to adjust for selection bias and estimate the effectiveness of pembrolizumab. The inverse probability weights were estimated using an ensemble machine learning technique, Super Learner, based on age, gender, race, practice type and smoking history. Adjusted hazard ratios (aHR) were estimated using weighted Cox proportional hazards models. Stratified analysis was conducted by ECOG PS (2 vs >2). Results: 217 (16%) individuals with advanced NSCLC and high PD(L)-1 expression received no treatment, compared to 546 (39%) individuals who received 1L pembrolizumab. The no-treatment group had a lower proportion of ECOG 2 compared to the pembrolizumab group (Table). Median rwOS in the no-treatment group was 2.4 months, compared to 7.1 months in the pembrolizumab group (p<0.001). In unadjusted survival analyses in the entire cohort and in cohorts stratified by ECOG status, treatment with pembrolizumab was associated with a significantly lower risk of death (hazard ratio [HR]: 0.38, 95% Confidence Interval [CI]: 0.31-0.45). In adjusted analyses, individuals treated with pembrolizumab had improved survival (HR: 0.40, 95% CI: 0.35-0.45). Conclusions: Our analysis of real-world clinical oncology data demonstrated that 1L treatment with pembrolizumab was associated with significantly improved rwOS among individuals with ECOG ≥ 2. [Table: see text]
The COVID-19 pandemic led to a reduction in cancer services in Australia.
Authors: Biondi Christine , Milch Vivienne , Nguyen Van , Ryan Regina , Roder David , Woods Alan , Cooper Kristie , Wang Rhona , Anderiesz Cleola , Keefe Dorothy Mary Kate 
Published: June 2021

e18812 Background: Australian oncologists reported dramatic decreases in cancer referrals during the pandemic. As real time data were difficult to acquire, Cancer Australia used surrogate measures to infer where reductions in medical services occurred. We analysed data available through the Medicare Benefits Schedule (MBS), a list of the medical services and professional attendances subsidised by the Australian Government, for the five highest incidence cancers: breast, colorectal, lung, prostate, and skin cancers. Methods: We identified over 500 MBS item codes for diagnostic and treatment procedures for malignancies and pre-cancerous conditions. Item codes were categorised into analysis groups based on cancer type and/or similarities in type of service. Data were examined at national and jurisdictional levels for 2020 to determine reductions during the initial COVID-19 period and to monitor subsequent recovery. Data were compared to 2019 to account for normal seasonal variation. Results: Australia’s first wave of the pandemic ran from March to May, and a second wave in the state of Victoria alone ran from July to September 2020. We observed notable reductions across all diagnostic and surgical procedure groups examined, with initial reductions observed between March and April for diagnostic procedures, and a one-month delay for surgical procedures, between April and May. Some services showed an initial recovery in May, with many showing partial or full recovery by June. For some groups, analyses showed sustained reductions over the 12-month period. While COVID-19 case numbers were greater during the second wave, the impact on services was less pronounced, likely owing to more refined policy approaches to managing health system and workforce capacity. There was further recovery by September for some but not all services. Similar patterns of change were observed across all Australian states and territories, with some variation by jurisdiction. Conclusions: The pandemic has impacted the delivery of cancer care. Any potential delays in diagnoses and treatment due to these reductions in services may lead to more advanced cancer stage at diagnosis and poorer patient outcomes including recurrence and survival. Impact of COVID-19 on selected cancer services in Australia in 2020.[Table: see text]
Patient out-of-pocket savings with lower-dose trastuzumab.
Authors: Dreyer Marie S. , Kacew Alec , Hsieh Po-Hung , Serritella Anthony , Knoebel Randall W. , Nanda Rita , Strohbehn Garth William , Ratain Mark J. 
Published: June 2021

e18828 Background: Trastuzumab-related costs of human epidermal growth factor receptor 2 (HER2) positive breast cancer treatment are significant, approaching $70,000 per patient in the adjuvant setting alone. Recently developed population pharmacokinetic models demonstrate that therapeutic levels of trastuzumab are maintained despite decreased maintenance dose or dose frequency, potentially improving trastuzumab’s value proposition. In this observational study, we evaluate the potential patient- and health system-level financial implications of low-dose trastuzumab. Methods: We identified 196 individuals who received treatment for HER2-positive breast cancer with trastuzumab or its biosimilars at a single urban comprehensive cancer center between January 1, 2017 and October 31, 2019. We estimate, using publicly available information, patient-experienced out-of-pocket costs using deterministic modeling under different conditions corresponding to changes in dosing practices, geographic site of trastuzumab administration, patient employment status, intent of treatment, and billing procedures, as well as Medicare cost-savings estimates. Results: Both reducing the maintenance dose of trastuzumab from the FDA-labeled dose of 6 mg/kg to 4 mg/kg Q3W and reducing maintenance dose frequency of trastuzumab from 6 mg/kg Q3W to Q4W were each associated with significant patient savings on drug- and administration-related out-of-pocket costs. Depending on billing practice and clinical scenario, patient savings as a percentage of total costs were 9-20% (neoadjuvant), 17-22% (adjuvant), and 14-19% (metastatic) with 6 mg/kg Q4W dosing. Similarly, 4 mg/kg Q3W dosing had savings of 15-25% (neoadjuvant), 19-28% (adjuvant), and 13-28% (metastatic). Utilization of off-label dosing regimens could result in $2.69 billion USD in annual Medicare spending on trastuzumab, an estimated savings of $670-810 million USD. Conclusions: Meaningful patient-level and system-level financial savings in the treatment of HER2-positive breast cancer can be achieved using pharmacokinetically near-equivalent low-dose or reduced frequency maintenance trastuzumab dosing. Given the significant potential savings, further prospective studies aimed at reducing dose or frequency of monoclonal antibodies in the treatment of cancer are warranted.
Evaluating differential cost growth across individual cancers: Insights from Oncology Care Model data.
Authors: Chaudhry Basit Iqbal , Gordan Lucio N. , Yue Andrew , Tran Lisa , Connor Nora 
Published: June 2021

e18853 Background: Analyzing cost growth in oncology often faces significant challenges, including fragmentation of data for infused vs. oral agents and ascertaining the cost of inpatient care. How differential cost growth at the individual cancer level contributes to aggregate cost growth in oncology is often opaque. We leverage the integrated claims data provided by Medicare for its Oncology Care Model (OCM) pilot to analyze variations across individual cancers with respect to cost growth. Methods: OCM’s innovative methodology creates a natural experiment where costs are compared against a counterfactual comprised of Medicare patients seen in non-OCM practices. Leveraging this differential counterfactual provides an opportunity to gain insight into cost growth for individual cancers compared to oncology as a whole. Specifically, cost growth is measured each Performance Period (PP) with respect to the Baseline Period, from 2012 to 2015. We analytically decomposed and remodeled key quantitative factors in OCM associated with cost dynamics in oncology, including the Trend Factor (TF), which represents non-OCM cost growth. From 124,896 episodes, we sampled with replacement 19,191 episodes from 17 practices between PP1 and PP6 using empirical data distributions. We assumed neutral novel therapy and experience adjustments and then compared the overall TF to the remodeled cancer-level TF, reaggregated from the individual episodes. Results: Reallocating the TF reveals that cost growth among cancer types is highly variable in the broader Medicare population. Cost growth at the individual cancer level varied from +99.3% to -14.3%. Of the 21 OCM cancers, 18 have TFs greater than zero, indicating cost growth in the non-OCM Medicare population since the Baseline Period. Four have a TF greater than 50%. Three cancer types show decreasing costs relative to the baseline period: intestinal cancer, MDS, and CNS tumor. Conclusions: Significant variation exists across individual cancer subtypes in terms of cost growth. Aggregate analyses of cancer at large have insufficient specificity to rationalize payment mechanisms. Payment reform efforts within cancer care should directly address dynamics at the individual cancer or cancer subtype level in order to provide more valid considerations for expected resource utilization, including in future payment policies. [Table: see text]
A population-based study of acute panmyelosis with myelofibrosis in the United States: 2004 to 2015.
Authors: McLaughlin Nicole , Ruan Gordon , Day Courtney N. , Harmsen William S. , Smith Caleb J. , Binder Moritz , Gangat Naseema , Go Ronald S. , Tefferi Ayalew , Shah Mithun Vinod 
Published: June 2021

e19003 Background: Acute panmyelosis with myelofibrosis (APMF) is a rare subtype of acute myeloid leukemia characterized by acute panmyeloid proliferation with increased blasts, cytopenias with bone marrow fibrosis, and absence of splenomegaly. There is a paucity of population-based studies of APMF. Methods: We queried the United States Surveillance, Epidemiology, and End Results (SEER) database and National Cancer Database (NCDB) using the ICD-O-3 code 9931/3. The SEER 17 registries (2004-2015) were used to find data on incidence. For NCDB data, comorbid disease burden was calculated using the Charlson-Deyo Score (CDS). Hazard ratios (HR) with confidence intervals (CI) were calculated using a Cox proportional hazards model. Overall survival (OS) was estimated with the Kaplan-Meier method. Variables significant in univariable analysis were included in a multivariable analysis. Results: We identified 260 APMF patients using the SEER database. Incidence was 0.3 cases/million individuals and did not change significantly from 2004-2015. With a median follow up of 6.9 years (95% CI 6.1-7.8), the median OS was 2.3 years (95% CI 1.7-2.8). We identified 530 APMF patients using the NCDB. The median age at diagnosis was 67 years (range 22-90) and 311 (59%) were male. With a median follow up of 5.0 years (95% CI 3.0-7.6), the median OS was 2.3 years (95% CI: 0.8-6.5). OS was 69%, 31%, and 18% at 1-, 5-, and 10- years, respectively. Patients diagnosed in 2012-2015 had a significantly improved OS compared to those diagnosed in 2004-2007 (HR 0.65, 95% CI 0.49-0.85; p=0.002). 271 patients (53%) patients received chemotherapy. The OS for those that received chemotherapy was 70% at 1 year and 30% at 5 years versus 70% and 32% at 1- and 5- years for those who did not ( p=0.99). The median time to chemotherapy from time of diagnosis was 25 days (range 0-532 days). 52 patients (10%) underwent transplantation and the OS of those patients was 90% at 1 year and 45% at 5 years versus 67% and 29% at 1- and 5- years for those who did not (HR: 1.7 (95% CI: 1.2-2.6), p=0.006). In univariable analysis, factors predicting inferior OS were age ≥ 65 years old at diagnosis (HR 1.8, 95% CI 1.5-2.3; p<0.001), male sex (HR 1.5, 95% CI 1.2-1.8; p<0.001), CDS ≥ 1 (HR: 1.5 (95% CI: 1.2-2.0), p<0.001), government insurance (HR 1.8, 95% CI 1.4-2.3; p<0.001), diagnosis at a non-academic facility (HR 1.6, 95% CI 1.2-2.0, p<0.001), and not receiving a hematologic transplant (HR 1.7, 95% CI 1.2-2.6; p=0.006). Multivariable-adjusted analysis is shown in the Table. Conclusions: The overall incidence of APMF has not changed between 2004 and 2015, but OS for 2012-2015 was improved compared to 2004-2007. Age ≥ 65 years old, male sex, CDS ≥ 1, and diagnosis at a nonacademic facility predicted inferior OS. Multivariable-adjusted analysis.[Table: see text]
Code status transitions in patients with high-risk acute myeloid leukemia (AML).
Authors: Abrams Hannah Rebeccah , Nipp Ryan David , Traeger Lara , Lavoie Mitchell W. , Reynolds Matthew J. , LeBlanc Thomas William , El-Jawahri Areej 
Published: June 2021

e19009 Background: Patients with high-risk AML often experience aggressive medical care at the end of life (EOL) such as hospitalization and intensive care unit (ICU) admission. Despite this, studies examining code status transitions in this population are lacking. Methods: We conducted a mixed methods study of 107 patients with high-risk AML enrolled in supportive care studies at Massachusetts General Hospital between 2014-2019. High-risk AML was defined as 1) new diagnosis > 60 years or 2) relapsed/refractory AML. Two physicians used consensus-driven medical record review to characterize code status transitions. Code statuses were coded as ‘full’ (confirmed or presumed), ‘restricted’ (i.e., do not resuscitate), or ‘comfort measures only’ (CMO); confirmations of presumed status were not coded as transitions. Results: At diagnosis of high-risk AML, 91.9% of patients were ‘full code’ (48.5% presumed, 43.4% confirmed) and 8.1% had restrictions on life-sustaining therapies. Overall, 55.1% (59/107) of patients experienced a code status transition, with a median of two transitions (range 1-4). Median time from first to last transition was 11 days (range 1-306) and from last transition to death was 1 day (range 0-11). Most of these transitions (79.6%; 48/59) were transitions to CMO near EOL. We identified three processes leading to code status transitions (Table): 1) pre-emptive conversations prior to any clinical change (15.3%; 9/59); 2) anticipatory conversations at the time of acute clinical deterioration (15%; 9/59); and 3) futility conversations after acute clinical deterioration, focused on withdrawing life-sustaining therapy (64.4%; 38/59). Only 55.9% (33/59) of patients participated in their last code status transition and 22.0% (13/59) of these transitions occurred in the ICU or Emergency Room. Conclusions: Most patients with high-risk AML had code status transitions at EOL, often following clinical deterioration that limited their ability to engage in EOL discussions. Interventions to promote earlier and more specific code status conversations are needed to improve patients’ ability to voice their EOL preferences.[Table: see text]
First-line treatment outcomes of CML patients in a real-world data setting in Lebanon.
Authors: Nasr Fadi , Yehia Intissar , El Khoury Reem , Diab Saada , Ghoche Ahmad , Nasr Lewis 
Published: June 2021

e19031 Background: BCR–ABL-targeting tyrosine kinase inhibitors (TKIs) constitute the cornerstone of treatment of CML leading to a life expectancy that is currently very close to that of age matched individuals in the general population. The aim of the current study was to describe aspects of CML in a real world data setting in Lebanon including responses to first lines with a specific focus on the impact of first-line treatment with imatinib compared to that of the second-generation TKI, dasatinib and nilotinib. We also evaluated what proportion of patients become eligible to attempt to stop their TKI treatment. Methods: Chronic myeloid leukemia registry was analyzed to evaluate response rates in the first line and eligibility for a treatment cessation attempt in adults diagnosed between 2003 and 2019. The registry covered 60 patients. 46 eligible patients were included in the study. BCR-ABL1 levels of ≤ 0.1%, ≤0.01% and ≤0.0032% on the international scale were defined as the molecular response end-points major molecular response(MMR), MR4.0 and MR,4.5 respectively. In the case of a switch in TKI therapy, the clinical chart was reviewed for the reason why the treating physician had changed the therapy (‘treatment failure’ or ‘TKI intolerance’). For the determination of eligibility to stop TKI, the inclusion criteria for the EURO-SKI trial were applied. Results: Seventy-two percent of the patients were treated with imatinib, 28% with a second-generation tyrosine kinase inhibitor (nilotinib and dasatinib). 15% of patients had discontinued their first-line treatment, mainly due to intolerance (10%) or treatment failure (5%). At 24 months, deep molecular response (MR 4.0 and MR4.5) were achieved at 16.7% and 38.9% respectively for imatinib, and at 22.2% and 33.3% respectively for second generation (p=1). The 5-year cumulative incidence of eligibility for a tyrosine kinase cessation attempt, according to EURO-SKI criteria, was 37%. Conclusions: In the current study we report the experience in CML from two health care institutions in Beirut, Lebanon. Our findings showed no statistically significant difference in response between the first and second generations. The criteria for an attempt to stop tyrosine kinase inhibitor therapy are met by a third of the patients.
Integrative structural variant and breakpoint detection using optical genome mapping in a patient with a transformed diffuse large B-cell lymphoma from chronic lymphocytic leukemia.
Authors: Wang Jiachi , Pang Andy , Hong Karl , Lai Jill , Roychoudhury Dipa , Murata-Colllins Joyce L 
Published: June 2021

e19511 Background: The finding of complex karyotypes has been a clinically significant finding in cancers of advanced stage or during cancer progression. Conventional cytogenetic and FISH analyses have been limited by the low-resolution of chromosomes and the number of FISH probes which can be implemented in one assay. Recent study revealed the potential of using optical genome mapping to decipher the architecture of cancer genome at nucleotide level. Methods: Karyotyping, FISH and optical genome mapping of bone marrow specimen. Results: We reported on a 63-year-old female with chronic lymphocytic leukemia for nine years and transformed to diffuse large B-cell lymphoma (DLBCL). The karyotype revealed a hypodiploid chromosomal complement: 42,X,-X,der(2)t(2;?;8)(p25;?;q11.2),t(2;9)(q3?5;p2?2),der(4)t(4;?;8)(p16;?;q11.2)t(4;15)(q35;q15),-8,-15,dic(17;21)(p11.2;p11.2),der(18)t(8;18)(q21.2;p11.32)[12]/46,XX[8]. FISH analysis showed loss of TP53, monosomy 8 with 3-5 copies of the Myc genes. Optical genome mapping analysis revealed 12 insertions, 29 deletions, 8 duplications, 6 intrachromosomal translocations and 12 interchromosomal translocations. Whole genome analysis identified multiple gains of 2p, 8p and 8q, losses of 9p, 15q and 17p. The breakpoints of two unbalanced translocation and one complex chromosomal rearrangement have been narrowed down to nucleotide resolution: ogm[GRCh37] t(2;9)(q34;p21.2) g.[chr2:211,281,003::chr9:26,532,620], ogm t(2;8)(p25.3;p23.3) g.[chr2:15,924::chr8:215,177] and ogm der(4)t(8q24.3→8q21.13→2p24.2→2q34→4p15.2→4q34.3→15q15.1) g.[chr8:80,461,191::chr2:18,079,530→chr2:211,274,379::chr4:26,381,729→chr4:180,989,408::chr15:42,404,514]. Conclusions: Integrative analysis using conventional cytogenetic and molecular cytogenomic methodologies unveil the complex architectural alterations of caner genome. The resolution achieved by optical genome mapping would potentially lead to discovery of carcinogenic mechanisms, new fusion genes, prognostic and therapeutic markers.
A retrospective study of efficacy and safety of mechlorethamine, vindesine, liposomal doxorubicin, and prednisone (MODP) in relapsed/refractory classical Hodgkin lymphoma.
Authors: Zhou Min-Hang , Wang Chunmeng , Liu Yang , Ku Wenjing , Yang Qingming , Han Weidong 
Published: June 2021

e19516 Background: There are few optimized therapeutic options for relapsed and/or refractory classic Hodgkin’s lymphoma (r/rCHL), especially in patients who failed in treatments of autologous stem cell transplantation (ASCT), brentuximab vedotin or even immune checkpoint blockage. Therefore, we developed a chemotherapeutic scheme to evaluate the efficacy in r/rCHL patients with previous various lines of therapies. Methods: Between January, 2014 and December, 2019, a retrospective study was performed on r/rCHL patients from Chinese PLA general hospital who were treated with MOAP regimen consisting of mechlorethamine 6mg/m2, vindesine 4mg, liposomal doxorubicin 15mg/m2 on days 1 and 8, prednisone 1mg/kg per day on days 1 to 10 (MOAP) every 4 weeks. CT or PET/CT were done every two cycles to assess the response. Patients treated with MOAP regimen and complete clinical data were included. Patients with less than two cycles of MOAT or unavailable response assessment were excluded. The primary endpoint were complete remission (CR) and progression-free survival (PFS). Results: A total of 87 patients were included and five patients were excluded, so 82 patients were eligible in the study. The median previous lines and cycles of chemotherapy was 2 (range, 1-7), and 9 (range, 3-31), respectively. All the eligible patients received MOAP regimen for a median 4 cycles (range from 2 to 8), and overall response rate (ORR) was 87.8% including 40 patients in CR (48.8%) and 32 in PR (39.0%). In patients with ≥ 3 lines or ≥ 10 cycles of chemotherapy, up to 50.0% and 41.0% of patients achieved CR, respectively. In patients with previous ASCT, 31.6% of patients also achieved CR. Patients with previous checkpoint inhibitors had even higher CR than those without checkpoint inhibitors, though not significantly (51.6% vs. 47.1%, p = 0.689). Median PFS in patients with CR, PR and SD/PD were 43.8 months, 9.6 months and 6.1 months, respectively (p = 0.000).Patients with < 3 previous lines of chemotherapy had a favorable PFS than those with ≥ 3 previous lines (not reached vs. 14.4 months, (p = 0.032). No differences in PFS were observed in terms of previous cycles of chemotherapy, ASCT and checkpoint inhibitors. Grade ≥ 3 adverse events included 37 leukopenia (45.1%), 16 lung infection (19.5%), 11 anemia (13.4%), 4 thrombocytopenia (4.9%), 3 febrile neutropenia (3.7%) and 3 increased transaminase (3.7%). Conclusions: The MOAP combination regimen produced a favorable CR in r/rCHL failing or progressing on ASCT, checkpoint inhibitors, multiple cycles or lines of chemotherapies. It is an effective salvage regimen in heavily pretreated r/r CHL.