bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality indicators for glioblastoma treatment: An audit from a tertiary care cancer center in India.
Authors: Goyal Love , Chakraborty Santam , Saha Saheli , Roy Paromita , Zameer Lateef , Mishra Deepak , Parihar Mayur , Chandra Aditi , Arunsingh Moses , Chatterjee Sanjoy , Mallick Indranil , Bhattacharyya Tapesh , Biswas Bivas , Basu Achari Rimpa 
Published: June 2021

e18659 Background: Surgery followed by chemoradiotherapy with temozolomide (TMZ) is the standard of care for glioblastoma. There are limited reports of quality metrics in glioblastoma. We present an audit of adherence to selected quality indicators proposed in the PRIME Quality Improvement study. Methods: Retrospective audit of quality indices for glioblastoma patients treated between 2017 - 2020. Patients were treated within a standard protocol of postsurgical integrated molecular diagnosis, radiotherapy with concurrent and adjuvant TMZ. Multiparametric MRI at predefined time-points of pre- and post radiation, interim and end of adjuvant TMZ guided management. Demographic, clinical, pathological, imaging, therapy and outcomes data was abstracted. Numbers with proportions for indices were calculated. Survival was estimated using the Kaplan Meier method. Results: Ninety-four glioblastoma patients were treated from 2017 to 2020. Quality metrics are reported (table). Patients in whom adjuvant TMZ could not be started or continued for 6 cycles had progressive disease and salvage chemotherapy was initiated. The 12 month overall and progression free survival was 74.6% (95% CI : 65.4% - 85.1%) and 43.6% (95% CI : 33.8% - 56.3%) respectively. Conclusions: Our patients met quality indices in most domains; outcomes are comparable with global results. These metrics will be periodically evaluated and updated to include newer standards to assess our continued service appropriateness.[Table: see text]
Real-world trends in biosimilar prescribing among oncology providers, 2019-2021.
Authors: McGlynn Kelly A. , McGarry Jacqueline , Patel Kashyap B. , Clinton Natasha 
Published: June 2021

e18701 Background: The number of approved biosimilars in the United States has increased exponentially in recent years. Within the oncology market, there are currently 14 approved biosimilars, with 11 launched since the start of 2019. The emergence of new oncology biosimilars provides a tool for success in value-based care, and has the potential to lower costs to patients and providers and expand access to care. Methods: Analysis of biosimilar prescribing behavior was performed using 2020 prescription data (Wolters Kluwer, n = 130,836), sales data (IQVIA), and dosage data for patients taking bevacizumab, trastuzumab, rituximab, or an FDA-approved biosimilar for these products (FDA Purple Book), between 2019-2021 (ION Solutions, n = 69,884). Drugs not directly interchangeable with the bevacizumab, trastuzumab or rituximab reference products according to NCCN guidelines were excluded. Results: Biosimilar products are currently available for bevacizumab (2 biosimilars), rituximab (3 biosimilars), and trastuzumab (5 biosimilars). We found that in 2020, 8.2% of new prescriptions for any of these three reference products were for a biosimilar. An analysis of real-world drug administration data revealed that in the 3 months following the 2019 launch of trastuzumab’s first biosimilar (trastuzumab-anns), 7.3% of initiating line 1 patients were prescribed the biosimilar over the reference product. During the same period in 2020, when a total of 5 trastuzumab biosimilars were available, 80.5% of initiating line 1 trastuzumab patients began treatment on a biosimilar, suggesting rapid uptake by providers. However, this differed by product, with the initial uptake for the first rituximab biosimilar (rituximab-pvvr), at only 2.3%. Uptake also occurred within treatment lines, with 11.1% of all patients (bevacizumab: 11.3%, trastuzumab: 14.1%, rituximab: 7.9%) switching from a reference product to a biosimilar during treatment. Uptake was particularly rapid for trastuzumab biosimilars: among patients on trastuzumab at the time of its first biosimilar launch, 18.2% switched to trastuzumab-anns in the first 90 days post-launch. Biosimilars launched at significantly lower prices than their reference products, with cost per prescription at -42.0%, -29.9% and -89.5% relative to the reference product for trastuzumab, rituximab and bevacizumab, respectively. However, biosimilar launches had little impact on reference product pricing, with 2019-2020 year-over-year (YOY) differences in price per prescription close to the YOY averages in previous years (2015-2019) for all three reference products. Conclusions: We conclude that uptake of biosimilars among oncology providers between 2019-2020 was rapid, although the extent of biosimilar prescribing varied among products. Biosimilars offered greatly reduced costs to providers, although reference product prices remained stable despite increased biosimilar competition.
Clinical relevance of comprehensive genomic profiling for advanced cancers in India.
Authors: Elizabeth Joseph Serena , Mathew Aju , Rajappa Senthill J. , Rohatgi Nitesh , Sirohi Bhawna , Jain Reetu , Agarwala Vivek , Shukla Deepak Kumar , Mehta Anurag , Pramanik Raja , Talwar Vineet , Maka Vinayak , Raut Nirmal Vivek 
Published: June 2021

e18718 Background: Comprehensive genomic profiling (CGP) assay, a next-generation sequencing (NGS) based technique generates a large amount of genomic information about a cancer. While CGP is increasingly used in low-middle income countries (LMIC), little is known about the extent to which these benefits patients. Here we describe the proportion of patients with advanced cancer in India who eventually receive targeted therapy for an actionable genetic alteration identified on CGP assays. Methods: This was a multicenter, retrospective cohort study in adult patients with advanced non-hematological malignancies who underwent a CGP test. We excluded patients who were identified to have a genetic alteration that has a well-validated targeted standard-of-care therapy (e.g.; EGFR exon 18, 19, 21 mutations for lung cancer, HER2 amplification for breast cancer). Participating oncologists provided anonymized information of consecutive CGP test reports through an online data capture form. Descriptive statistics were used to describe the proportion of patients with subsequent targeted therapy. Results: During 2019-20, 12 medical oncologists provided CGP reports for 297 patients; 235 met the inclusion criteria. Fourteen different testing panels were used by the oncologists. Among the study cohort, 45% were male. Eighty nine percent underwent tumor tissue biopsy and 11% had liquid biopsy. The most common cancers were lung (19%), breast (18%), pancreatobiliary (9%) and colorectal (6%). Patients received a median of 2 lines (range: 0-5) of prior systemic therapy. Based on the CGP assay, 35 patients (15%) received targeted therapy. Among them, 29% was for HER2 amplification (non-breast cancer), 26% for PIK3CA mutation, 11% for HER2 or EGFR exon 20 insertion mutation (lung cancer), 5% each for BRAF mutation (non-melanoma), EGFR mutation (non-lung cancer) and MET mutation. Conclusions: In a LMIC setting, 15% patients received a targeted therapy based on CGP assay. This is comparable to reports from high income countries. Considering the limited access to new drugs and clinical trials, this finding requires further analysis.
Seminomatous and non-seminomatous mediastinal germ cell tumors (MGCT): A real-world analysis from two tertiary care centers in India.
Authors: Sharma Aparna , Biswas Bivas , Reddy Rohit , Thumbudorai Robin , Ganguly Sandip , Dabkara Deepak , Pramanik Raja , Kumar Sunil , Sahoo Ranjit Kumar , Sharma Atul , Kumar Lalit , Batra Atul 
Published: June 2021

e18726 Background: Mediastinal germ cell tumor (MGCT) is a rare entity and comprises 10-15% of all mediastinal tumors. We describe the real-world treatment patterns and outcomes of MGCT treated at two tertiary care centres in India. Methods: Patients diagnosed with GCT (any site) at two large tertiary care centres from January 2010 to December 2020 in India were identified using the ICD-09 code (C-62) from prospectively kept databases. From these databases, a manual search was performed to identify MGCT patients. A chart review was done to retrieve demographic, tumor-related (serum tumor marker levels as per International germ cell cancer consensus (IGCCC)) and treatment details. Relapse free survival (RFS) and overall survival (OS) were estimated and compared for seminomatous and non-seminomatous MGCT. Results: A total of 54 patients were identified and all were males with a median age of 25 years (interquartile range, 18-45). Common presenting symptoms included cough (81.4%) shortness of breath (64.8%), chest pain (25.9%), superior vena cava obstruction (20.3%), pleural effusion (18.5%) and pericardial effusion (5.6%). Approximately one-thirds (n = 17) were seminomatous, while two-thirds were non-seminomatous (n = 37). Serum tumors markers levels were S0 (7.4%),S1 (42.6%),S2 (29.6%) and S3 (20.4%). Treatment was primarily by multiagent chemotherapy [ Bleomycin/Etoposide/cisplatin(BEP) 63.0%, EP (Etoposide/Cisplatin) 18.5%, VIP (etoposide/ifosfamide/cisplatin) 13.0%). Median number of cycles administered was 3 (Range 1-6). Three patients did not receive chemotherapy (all seminoma) and were treated with upfront surgery. In total, 11 patients (20.4%) underwent surgery, and eight (14.8%) received radiation. Three patients were not evaluable for response, 33.3% achieved complete response (CR),44.4% achieved partial response (PR), 9.3% had SD (stable disease) and 7.4% progressed on first line chemotherapy. Median follow up was 14.4 months (95% confidence interval [CI] 9.03 -26.16). Three year relapse free survival was 64.0% in overall population, and 100% in seminoma vs 41.5% in non-seminoma (P < 0.001). Three year OS was 80.2% in all patients and 94.1% for seminoma versus 70.0% in non-seminoma (P = 0.178). Conclusions: In this largest real-world analysis of MGCT, we found excellent long-term survival rates for patients with seminomatous MGCT, while further optimization of treatment is needed for those with non-seminomatous MGCT.
Costs, throughput time, and proportion of valid test results, a model-based analysis of liquid biopsies for stage IV non-small cell lung cancer.
Authors: Koole Simone N. , Schouten Robert , Vessies Daan , Schuurbiers Milou , Bosch Linda J.W. , van den Heuvel Michel , van Harten Wim , van den Broek Daan , Monkhorst Kim , Retel Valesca P. 
Published: June 2021

e18844 Background: Tissue diagnostics for metastasized non-small cell lung cancer (NSCLC) is hampered by the difficulty of obtaining tissue biopsies, and sequential testing. This leads to patient burden, and a time-consuming diagnostic trajectory, sometimes without valid test results. We analyzed the diagnostic process of liquid biopsies (ctDNA) as an addition to tissue diagnostics, for patients with stage IV NSCLC. Methods: Data was retrieved from stage IV patients (N=209) included in the observational, Lung cancer Early Molecular Assessment trial (LEMA; NCT02894853). Within this study, plasma and tissue was collected upfront. Sequencing of ctDNA was performed retrospectively, and compared to results from tissue diagnostics, as performed in the including hospital, including test results, success-rates, and identified targets per patient. Throughput time for tissue, and costs for diagnostics were calculated within a single specialized institute. Because of the retrospective nature of the ctDNA assessment, diagnostics for implementation of ctDNA was modelled (1 run per week), based on estimations for the trajectory and throughput time. A discrete-event simulation model was developed with three scenarios: 1) diagnostics with tissue biopsy alone (comparator); 2) diagnostics with ctDNA first, and tissue biopsy if required; 3) ctDNA if biopsy failed. The process scope ranged from tissue/blood retrieval to outcome in terms of targets. Simulation analysis was performed, calculating mean price per patient (pp), median throughput time pp, and targets found per scenario. Results: In scenario 1, 85% of the patients had a clinically relevant test result, compared to 93% and 92% when ctDNA was added in scenario 2 and 3, respectively. Scenario 2 was the fastest, but also the costliest scenario: median throughput time 15 days pp (IQR 8-30) and mean costs of €2.716 pp (standard deviation [SD] €789) (Table). In this scenario, 9.9% of the biopsies could be cancelled, and in 39.6% a simple biopsy with immunohistochemistry was sufficient. Conclusions: The addition of ctDNA may lead to better informed treatment decisions in patients with stage IV NSCLC. Discrete-event simulation analysis showed that the addition of ctDNA in the diagnostic process increased proportion of patients with a clinically relevant test-result in both scenarios. Throughput time is faster, and additional costs per patient are limited, especially when ctDNA is added after biopsy failure. Clinical trial information: NCT02894853. [Table: see text]
Event free survival in adults with relapsed ALL who underwent front-line therapy with CALGB 10403.
Authors: Raychaudhuri Suravi , Yurkiewicz Ilana , Mannis Gabriel N. , Medeiros Bruno C. , Coutre Steve E. , Muffly Lori S. , Liedtke Michaela 
Published: June 2021

e19005 Background: CALGB 10403 is a pediatric-inspired ALL regimen that has recently been shown to have improved survival rates in adolescents and young adults with ALL when compared to historical outcomes with traditional adult ALL regimens (Stock et. al, 2019). Methods: This is a retrospective cohort study of ALL patients who received induction CALGB 10403 at Stanford University (both on and off trial), achieved CR1, and subsequently relapsed. Primary outcome of interest was event free survival from time of diagnosis. Events were defined as relapse or death. Secondary outcomes were overall survival and event free survival from first relapse. Patients were censored at time of last clinical follow up. Results: 25 patients met inclusion criteria and received front-line CALGB 10403 from April 2010 to September 2018. At the time of initial diagnosis median age was 30 years (range 18 – 39 years). 68% of patients were male. 48% of patients were overweight and 40% were obese. 76% of patients had precursor B cell ALL while 24% had T cell ALL. 12% had CNS disease at diagnosis. 36% of patients had WBC greater than 30k. 12% of patients had CRLF2 rearrangement. 12% of patients were MRD positive after first induction. 20% of patients received rituximab. Median event free survival time from diagnosis was 20 months (range 3 – 79 months) and median overall survival time was 53 months. Blinatumomab was the most common salvage therapy after 1st relapse, followed by inotuzumab. 15 patients (60%) achieved CR2, of which 4 (27%) were MRD positive after 2nd induction. 15 patients (60%) went to HSCT. Of the patients who achieved CR2, 8 relapsed for a second time. Median event free survival time after first relapse was 23 months. Survival 1 year after relapse was 60%. 11 of the 25 patients were alive at last follow up. Median follow up time of survivors was 6 years. Conclusions: This is a descriptive retrospective cohort study of adult patients in a real world setting who received CALGB 10403 induction and subsequently relapsed. Compared to other studies of relapsed ALL patients who were induced with traditional chemotherapy (Fielding et. al, 2007), survival 1 year after relapse was much higher (60% vs. 22%). As CALGB 10403 becomes an increasingly common induction regimen for AYA and adults with ALL, further outcomes study is required.[Table: see text]
Improved transfusion independence rates for momelotinib versus ruxolitinib in anemic JAKi naïve myelofibrosis patients independent of baseline platelet or transfusion status.
Authors: Kiladjian Jean-Jacques , Platzbecker Uwe , Mayer Jiří , Illés Árpád , Prejzner Witold , Woźny Tomasz , Tzvetkov Nikolay , Vannucchi Alessandro M. , Kirgner Ilya , Nagy Zsolt , Grosicki Sebastian , Derolf Åsa , Lazaroiu Mihaela Cornelia , Yoon Sung-Soo , Goh Yeow Tee , von Bubnoff Nikolas , Verstovsek Srdan , Klencke Barbara J. , Donahue Rafe , Mesa Ruben A. 
Published: June 2021

e19039 Background: Momelotinib (MMB) is a potent JAK1, JAK2 and ACVR1 inhibitor with clinical activity against the hallmark features of myelofibrosis (MF), namely anemia, constitutional symptoms and splenomegaly, across the continuum of JAKi naïve or previously JAKi treated intermediate/high risk MF patients as demonstrated in the previously conducted Phase 3 SIMPLIFY-1 & -2 clinical trials (S1, S2). S1 was conducted in JAKi-naïve patients with MF (n = 432) double-blind randomized 1:1 to MMB or ruxolitinib (RUX). MMB demonstrated a statistically non-inferior splenic response rate (SRR) to RUX at the W24 landmark analysis in S1 but did not meet significance for total symptom score (TSS) response. Low SRR and TSS response was observed for RUX in patients with low platelets, while MMB elicited consistent SRR and TSS response across the platelet subsets, comparable to the response in the ITT. Transfusion independence (TI) at W24 was higher for MMB vs RUX patients across all PLT strata. Methods: Progressive anemia is a common occurrence in MF with nearly all MF patients requiring transfusions as their disease advances. Given the prognostic importance of Hgb and transfusion status in MF patients including evidence that achieving or maintaining transfusion independence by Week 24 with momelotinib is associated with improved OS in S1 and S2, we expanded the previously reported retrospective platelet subset analysis to explore the W24 TI response rates for MMB and RUX randomized patients in S1 by baseline Hgb and PLT levels and transfusion status. Results: The data presented here suggest that the prognostically-important W24 TI rate was substantively higher in anemic patients receiving MMB versus RUX, irrespective of the degree of anemia. MMB is also more effective relative to RUX in achieving or maintaining TI in JAKi naïve patients irrespective of baseline PLT count or baseline transfusion status. Conclusions: Together with data suggesting that TI response at W24 with momelotinib is associated with a survival advantage, these data further support the potential TI benefits of inhibiting ACVR1 in addition to JAK1 and JAK2 with MMB in MF patients. Clinical trial information: NCT01969838, NCT02101268. [Table: see text]
Pulmonary fungal infections in acute leukemias and aggressive lymphomas: Analysis of the United States National Inpatient Database.
Authors: Ozoya Oluwatobi , Ayuk Adaeze , Lawal Odunayo , Emole Josephine 
Published: June 2021

e19042 Background: For patients undergoing intensive chemotherapy, pulmonary fungal infections (PFI) represent a major cause of morbidity and mortality. Our study examined predictors and outcomes of PFI in hospitalized patients (pts) with hematological malignancies in the current era of antifungal prophylaxis for high-risk patients. Methods: Using the 2018 National Inpatient Sample (NIS) database, we conducted a retrospective study of hospitalized pts aged ≥ 18 years, with acute leukemias or aggressive lymphomas. Hospitalizations were selected using International Classification of Disease, Tenth Revision (ICD-10) codes for leukemias, lymphomas and PFI (candidiasis, aspergillosis, cryptococcus, and mucormycosis). Demographics, comorbidities, and outcomes were compared between pts with and without PFI using Chi-squared test. Multivariable logistic regression was performed to explore predictors associated with PFI. Results: Of 205,525 hospitalizations that met the inclusion criteria, PFI was diagnosed in 1635 (0.8%). Frequent infections were aspergillosis (80%) and candidiasis (11%). Pts with acute myeloid leukemia (AML) accounted for 64% of all PFI. The PFI group, compared to non-PFI, were more likely to be non-Caucasian (39% vs 32%, p<0.05), have higher Charlson comorbidity index (CI) [64% vs 55%, p<0.01], longer mean length of stay (23 vs 9 days, p<0.001), and more likely to have AML (64% vs 33%, p<0.001). Pts with PFI had higher odds of acute respiratory failure, severe sepsis, and in-hospital mortality. Mortality rates for PFI and non-PFI group were 17% and 6% respectively (p<0.001). Predictors associated with PFI were Hispanic or Native American race, Charlson CI ≥ 3, neutropenia, malnutrition, bone marrow transplant status and diagnosis of AML (Table). Conclusions: Our study identified clinical variables that predicted for PFI in patients with acute leukemias and aggressive lymphomas. Pts with these high-risk characteristics should get priority for close surveillance, mold-specific prophylaxis, and antifungal therapeutic drug monitoring. Selected predictors associated with pulmonary fungal infections. Adjusted Odds ratio (OR).[Table: see text]
Trichostatin A sensitivity signature across hematological cell lines.
Authors: Przychodzen Bartlomiej 
Published: June 2021

e19521 Background: Histone deacetylase inhibitors (HDACi) are small molecules that increase acetylation of lysine residues by blocking histone deactylases. These anticancer agents affect epigenetic and non-epigenetic gene expression resulting in cell cycle arrest of cancer cells. Furthermore HDACi can enhance its anti-tumor effects via the pharmacologic modulation of macrophage. Some HDACi’s such as Trichostatin A (TSA) can also affected the tumor immune microenvironment by suppressing the activity of infiltrating macrophages and inhibiting myeloid-derived suppressor cell recruiement (Li et al.,). Methods: We conducted a high throughput screen comparing gene expression profiles in known hematological cell lines to identify transcriptional signatures associated with TSA sensitivity obtained from GDSC. Results: We selected genes that showed at least 2fold expression difference and were statistically significant (p < 0.05). We identified 49 genes that were upregulated and 85 that were downregulated. The most significant results include multiple genes known to be correlated with the B-cell maturation process. We found that CD24 a small GPI linked glycoprotein expressed at the surface of most B lymphocyte precursors, neutrophils, epithelial cells and frequently found to be highly expressed in various hematological and solid neoplasms, was up/downregulatred by XX. Interestingly, CD24 plays a role in the activation and differentiation of the cells as bone marrow samples lacking CD24 resulted in decreased numbers of both pre-B and immature B-cell populations. We also found that IKZF2, a transcription factor regulating lymphocyte development and queiesence and which is frequently deleted in hypodiploid B-ALLs. This result could revelent as other reports suggest a role of IKZF2 as a tumor suppressor with a central role regulating the balance of self-renewal and differentiation in leukemic stem cells. Conclusions: Our study identified transcriptional profiles which suggest that TSA sensitivity could be related to B cell maturation. Further experiments warrant replication of these findings which could prove useful in creating optimal, TSA-based treatments acting either as potent single agents or in combination enhancing anti-tumor effects of immunotherapies.