bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare utilization and costs associated with first-line treatment with obinutuzumab- and rituximab-based regimens for follicular lymphoma.
Authors: Ta Jamie T. , To Tu My , Sud Cheryl , Shapouri Sheila , Seetasith Arpamas 
Published: June 2021

e19536 Background: Current real-world data on healthcare utilization (HCU) and costs of common first-line (1L) follicular lymphoma (FL) regimens, including obinutuzumab (G), remain limited. The aim of this study was to examine real-world HCU and costs for the most common National Comprehensive Cancer Network (NCCN)-recommended 1L FL treatments. Methods: This was a retrospective cohort study using administrative claims data from the IQVIA PharMetrics Plus and IBM MarketScan Commercial and Medicare Supplemental databases. We identified patients (pts) ≥18 years, who had ≥1 inpatient claim or ≥2 outpatient claims, with a diagnosis of FL from February 1, 2015 to March 31, 2020, and had received 1L FL treatment (per NCCN guidelines) between February 1, 2016 and September 30, 2019. The first claim for FL treatment was the index date. All pts had ≥12 months of pre- and ≥6 months of post-index continuous enrollment in medical and pharmacy benefits. Pts with other primary cancers, FL treatment, or stem cell transplant during the pre-index period, and clinical trial participation or end-stage renal disease during the study period were excluded. All-cause HCU and costs (2020 USD) per pt during the 6-month post-index period were reported for the five most common 1L FL regimens (only complete NCCN regimens were considered). Results: Overall, 1991 pts met the eligibility criteria, and 53% were male. The mean (standard deviation [SD]) age and Charlson Comorbidity Index at index were 58 (10.4) years, and 1.7 (1.0), respectively. The most common 1L regimens were rituximab-bendamustine (R-benda; n=818 [41.1%]), R-monotherapy (R-mono; n=592 [29.7%]), R-CHOP (n=461 [23.2%]), G-benda (n=86 [4.3%]), and R-CVP (n=34 [1.7%]). The proportion of pts who had ≥1 hospitalization or an emergency room visit was highest with R-CHOP (26.7% and 33.6%, respectively) and lowest with R-mono (11.3% and 18.1%, respectively). Mean (SD) all-cause total healthcare costs were highest with R-benda and G-benda, followed by R-CHOP, R-CVP, and R-mono (Table). Mean (SD) all-cause medical and FL treatment costs (drug and administration) were highest for R-benda ($174,407 [$110,520]; $135,520 [$96,492]) and lowest for R-mono ($87,368 [$83,910]; $54,271 [$40,433]). Conclusions: This real-world study provides an update on HCU and costs among pts initiating current NCCN-recommended 1L treatment for FL. Unadjusted 6-month total healthcare costs were highest with R-benda, followed by G-benda, while the lowest costs were seen with R-CVP and R-mono. Future studies with adjustment for pt characteristics are needed to compare HCU and costs between FL regimens.[Table: see text]
Parameters of cellular immunity in patients with lymphomas after COVID-19.
Authors: Kamaeva Inna A. , Lysenko Irina B. , Sagakyants Aleksandr B. , Bondarenko Elena S. , Shulgina Oksana G. , Nikolaeva Nadezhda V. , Kapuza Elena A. , Pushkareva Tatiana F. , Gaysultanova Yakha S. , Kit Oleg I. , Dmitrieva Viktoria V. , Velichko A. V. 
Published: June 2021

e19572 Background: The development of lymphomas is accompanied by disorders in the structural and functional organization of the immune system leading to immune deficiency. Such patients are at greater risk of severe SARS-CoV infection. Our purpose was to assess the parameters of cellular immunity in patients with lymphomas with a history of multi-course chemotherapy, therapy with anti-CD20+ antibodies and PCR-confirmed COVID19. Methods: The study included 12 adult patients with lymphoproliferative diseases (non-Hodgkin's large B-cell lymphomas (NHL) - 7, Hodgkin's lymphomas (HL) - 5) with a history of PCR-confirmed COVID-19. All patients underwent 4 to 6 chemotherapy cycles. The relative numbers of the main populations of leukocytes, T- and B-lymphocytes, as well as subpopulations of T-lymphocytes, were assessed in the whole blood collected in K2EDTA anticoagulant using the BD FACSCanto II flow cytometer with a panel of antibodies according to the manufacturer's instructions (Becton Dickinson, USA). Results: Patients with HL showed a number of changes in the parameters of cellular immunity. The content of total lymphocytes and monocytes was reduced in comparison with patients with NHL by 34% and 56%, respectively: 14.3 (11; 17) vs. 21.7 (15.2; 32), and 6.0 (4.8; 7.1) vs. 13.5 (12.9; 13.7), respectively. An increase in granulocytes by 30% was revealed in patients with HL. No differences were found in the content of both general and main populations (CD3+, CD3+CD4+, CD3+CD8+, central and effector memory cells). However, the content of naive CD3+CD4+ and CD3+CD8+ lymphocytes in patients with HL increased by 43% and 62%, respectively. While the number of CD3+CD4-CD8- lymphocytes was 47% lower, the number of CD3+CD4+CD8+, on the contrary, exceeded the values in patients with NHL by 4.6 times. Patients with HL also showed a tendency towards a decrease in the number of NK and NKT-lymphocytes. Conclusions: The increased levels of naive lymphocytes and both populations of memory cells and a sharp increase in double-negative T-lymphocytes and B-lymphocytes in patients with HL could indicate certain characteristics of the disease course affected by COVID-19. The data require additional research and can be used to assess the condition of patients and to predict the therapy efficacy.
Retrospective study to assess the impact of hepatitis C virus infection on the prognosis and management of multiple myeloma.
Authors: Kaldas David , Wahba Andrew , Azab Radwa Hamdy , Elnakoury Ehab Mostafa , Abdel Karim Nagla Fawzy , Abdel-Malek Raafat 
Published: June 2021

e20001 Background: Multiple Myeloma (MM) is a neoplasm of the post-germinal center, terminally differentiated B-cells. MM accounts for 1% of all types of cancer and 10% for all hematologic malignancies. Chronic hepatitis C virus (HCV) is an infection that affects over 71 million patients worldwide. Cytotoxic agents and immunosuppressive therapy as steroids are the main line of therapy in lymphoid malignancies, but these drugs may exacerbate chronic viral hepatitis and cause uncontrolled replication of hepatitis viruses. The impact of HCV infection on MM patients remains unclear. Objective: To assess the impact of HCV infection on the prognosis and management of MM patients. Methods: A 10-year retrospective study of MM patients was conducted at Cairo University Clinical Oncology Department from January 2009 to April 2019. Results: During this time, 150 patients were diagnosed with MM, 109 (72.7%) were HCV negative, 24 (16%) were HCV positive, and 17 (11.3%) with unknown HCV status. The median age was 51 and 54 years for HCV negative and positive groups respectively, with a statistically insignificant difference (p-value > 0.2). In the multivariate analysis, HCV infection was not an independent factor related to overall survival (OS), however age, creatinine and hemoglobin levels correlated significantly with OS (p < 0.009, 0.008, 0.031 respectively). The median OS for the HCV negative group was 31.11 months (95% CI: 22.62 - 39.61) compared to 37.66 months (95% CI: 7.19 - 68.13) for the HCV positive group. The median progression-free survival (PFS) for all patients was 18.9 months, for HCV positive patients was 15.36 months (95% CI: 13.18 – 17.54), and for HCV negative patients was 20.49 months (95% CI: 14.13 – 26.85). Age below 60 years and creatinine level less than 2 mg/dL were statistically significant for favorable disease-free survival (DFS) (p < 0.030, 0.034 respectively). Conclusions: Age, creatinine and hemoglobin levels are significant prognostic factors in MM but HCV status doesn’t affect the overall survival or progression-free survival. HCV infection should not contraindicate MM therapy.
Profile and management of toxicity of selinexor and belantamab mafodotin for the treatment of relapsed/refractory multiple myeloma: A systematic review.
Authors: Neupane Karun , Ehsan Hamid , Wahab Ahsan , Masood Adeel , Ahmed Tehniat Faraz , Bahram Saman , Hannan Abdul , Haider Mobeen Zaka , Shahzad Moazzam , Mushtaq Muhammad Umair , Anwer Faiz 
Published: June 2021

e20014 Background: Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of relapsed/refractory multiple myeloma on July 2019 and August 2020 respectively. The toxicity profile of these drugs is a concern since these are approved for use in patients who have already undergone multiple lines of treatment. Methods: Six studies for Sel and two for belamaf were included after a systematic search of PubMed, Embase, Cochrane, and Clinicaltrials.gov. Results: The most common hematological toxicity associated with these two drugs is thrombocytopenia. The common G-3/4 hematological AEs of Sel were thrombocytopenia (39%-71%), anemia (16%-33%), leukopenia (8%-33%) and neutropenia (9%-33%) whereas common G-3/4 non-hematological AEs were hyponatremia (5%-26%), fatigue (13%-15%), diarrhea (5%-10%), eye disorders (9%-10%), musculoskeletal disorders (4%-10%), elevated liver enzymes (10%), peripheral neuropathy (5%) and vomiting (2-4%). Keratopathy and anemia were the major toxicities of belamaf. Most of these toxicities are manageable. Treatment modifications and dose interruption are usually needed when AEs are more than grade II. REMS program guidelines is recommended for close monitoring and evaluation of Sel and belamaf toxicities and early ophthalmological intervention. Conclusions: As these are newer drugs with limited data, continuous surveillance and monitoring is warranted during the treatment course with early mitigation strategies. The physician should be aware of thrombocytopenia and its management as well as belamaf ocular toxicity which is manageable but if missed could have serious complications.[Table: see text]
Management of light chain deposition disease: A systematic review.
Authors: Masood Adeel , Shahzad Moazzam , Wahab Ahsan , Pachika Pranali Santhoshini , Ahmed Tehniat Faraz , Khanam Razwana , Ehsan Hamid , Neupane Karun , Amin Saher Nasir , Mushtaq Muhammad Umair , Anwer Faiz 
Published: June 2021

e20042 Background: Light-chain deposition disease (LCDD) is part of a wide spectrum of plasma cell proliferation disorders. LCDD predominantly affects kidneys by systemic deposition of congo red negative non-fibrillar light chains. Due to the rarity of disease, no prospective data is available, and clear guidelines don’t exist for the treatment. We reviewed data to summarize effective treatment strategies. Methods: A literature search was conducted on PubMed, Cochrane, and ClinicalTrials.gov with final update in November 2020 using terms ‘light chain deposition disease’, ‘therapy,’ and ‘disease management’. Library was manually screened to remove articles on LCDD in transplant kidneys. We identified 63 case reports/series and 11 retrospective studies n=365. Results: Retrospective Studies: 9 studies (n=283) identified various combinations of LCDD and plasma cell dyscrasias given the rarity of idiopathic LCDD. Lorenz et al. reported 6 patients (pts) that received ASCT with MEL preconditioning with 92% improved proteinuria and 95% improved eGFR. Pozzi et al. reported 63 pts (32% idiopathic LCDD, 65% concurrent MM and 3% concurrent CLL) where all pts received a combination of vincristine, doxorubicin, dexamethasone/methylprednisolone. 5/63 patients received ASCT. The median survival was 4.1 years. Bortezomib (V) based regimens: Most experts favor V based regimens to treat LCDD, but no dedicated trials exist. 26 case reports/case series (37 pts) included; 23 pts with idiopathic LCDD and rest with a concurrent disorder. Daratumumab: Milani et al. treated 8 pts with LCDD and concurrent MM with single agent daratumumab who failed at least one regimen. Autologous stem cell transplant (ASCT): 13 case reports/case series (20 pts) identified who received ASCT with melphalan (MEL) conditioning with/without various combinations of chemotherapies before and after ASCT. 14 pts had LCDD, and 6 pts had concurrent clonal cell dyscrasia. Miscellaneous regimens: Various other regimens showed promising results with improved renal functions but not well studied e.g., thalidomide and dexamethasone (Haruyuki et al.). Conclusions: Dedicated clinical trials are difficult given rarity of LCDD but needed. Bortezomib based regimens seem to be good options, ASCT with MEL conditioning is a suitable choice for younger and fit pts.[Table: see text]
Weekly osimertinib dosing to prevent EGFR mutant tumor cells destined to home mouse lungs.
Authors: Butle Ashwin , Joshi Asim , Noronha Vanita , Prabhash Kumar , Dutt Amit 
Published: June 2021

e20504 Background: The recent ADAURA trial concludes daily dosing of adjuvant osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), improves disease-free survival with stage IB/II/IIIA EGFR-mutated non-small cell lung cancerpatients in comparison to placebo. We have developed a preclinical orthotopic mouse model, using luciferase tagged lung adenocarcinoma cells harboring EGFR TKI sensitive exon 19 deletion, to model and extend trial implications comparing a weekly vs daily dosing outcome of osimertinib to a first-generation TKI- erlotinib. Methods: We present an assessment of the homing of PC9-luciferase cells to the lungs of mice injected through mouse tail vein. Thirty NOD-SCID mice were divided into five groups as follows: two groups each for daily and weekly treatment and one group for vehicle control. For all the mice in the respective groups, erlotinib (25 mg/kg) and osimertinib (15 mg/kg) was orally administered. Homing of cells in the lungs of mice was assessed by bioluminescence imaging regularly. Results: In the control group, 100% of the mice showed homing and retention of cells in the lungs of mice 18 days post-injection. In mice receiving erlotinib daily, homing of the cells in lungs was absent in all four mice, except in one mouse where emergence was observed after day eight post-injection. In the case of erlotinib weekly group, out of four only one mouse showed absence of homing of cells in the lungs of mice. Interestingly, 100% of the mice in both the groups receiving osimertinib daily or weekly showed complete absence of homing of cells in the lungs of mice from day 3 onwards post-injection (Table). The tumors observed in the lungs, when dissected at day 30, confirmed the colonization of the injected cells homing to the organ. Conclusions: Based on the complete absence of the homing of cells in lungs of osimertinib treated mice, in both weekly and daily regimens, adjuvant osimeritinib may represent a viable treatment option in delaying the onset of disease post resection of early stage tumors or among patients with pre-disposition to EGFR mutant lung cancers harboring germline EGFR mutations. In addition, low-dose once-a-week osimertinib could potentially have several advantages over daily dosing, including lower toxicity, affordability, ease of administration and delaying or preventing acquired resistance that remains to be explored. [Table: see text]
Relationship between loss-of-function mutation of the stromal antigen 2 gene and treatment in non-small cell lung cancer.
Authors: Zhuo Minglei , Liu Xin , Chen Rongrong , Xu Xiong , Ni Bin 
Published: June 2021

e20509 Background: The protein encoded by Stromal Antigen 2 ( STAG2) gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Loss-of-function (LOF) mutations of STAG2 gene are commonly detected in different tumors including non-small-cell lung cancer. However, there is no relevant research on the impact of STAG2 alterations on lung cancer treatment. Here we explored the correlation between the LOF of STAG2 and clinical features, concomitant genetic alterations and treatment in NSCLC pts. Methods: A total of 2882 NSCLC pts were enrolled. All the tissue samples were detected by DNA based next generation sequencing (NGS) with a 1021 gene panel. Clinical information was obtained synchronously from physicians and surgeons. According to whether LOF of STAG2 is detected, pts were divided into LOF subgroup and wild type (WT) group. Results: All pts enrolled are Chinese, and median age at diagnosis of them is 63±11.21. Compared to the WT subgroup, a higher average TMB was observed in the LOF group (12.64muts/Mb vs. 6.66mut/Mb, P＜0.05). Between the LOF group and the WT group, there were no significantly difference in all clinical baseline characteristics including age at diagnosis, gender, tumor stage and pathological type. At the time of sample collection, there was no significant difference between the two groups of pts whether they had received systemic treatment (chemotherapy, targeted therapy or immunotherapy) and systemic treatment, and the number of systemic treatment lines received. Neither significant differences in driver gene alteration and other accompanying mutations were observed in the two groups. Conclusions: In NSCLC pts, LOF of STAG2 is not a change after drug resistance, but it may lead to an increase in TMB, which indicates that these pts may have more benefits from immunotherapy. But the influence on prognosis of NSCLC pts needs further research to clarify.
Overexpression of LILRB2 (ILT4) is correlated with immunosuppressive immune infiltration in lung adenocarcinoma.
Authors: Li Butuo , Jiang Chao , Wang Shijiang , Li Xuanzong , Xu Yiyue , Fan Xinyu , Yu Jinming , Wang Linlin 
Published: June 2021

e20519 Background: Immune checkpoint inhibitors have revolutionized the patterns of tumor treatment with significantly improved survival. However, it’s worth noting that the objective response rate of PD-1/PD-L1 inhibitors monotherapy is just 20% in non-small cell lung cancer (NSCLC) patients, and biomarkers for the prognosis of patients receiving PD-1/PD-L1 inhibitors are urgently needed. LILRB2 (ILT4) is known as an immunosuppressive molecule and promotes the development and progression of NSCLC. However, the relationship between LILRB2 expression and immune microenvironment remains unclear in patients with lung adenocarcinoma. Methods: Expression profile and corresponding clinicopathological data of patients with lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) database. TIMER 2.0 was used to investigate the relationship between LILRB2 expression and immune infiltrates, including T cell subset, macrophage and so on. Cox proportional hazard model was also performed to evaluate the role LILRB2 expression and immune infiltrations in prognostic prediction of patients with lung adenocarcinoma. Results: 515 patients with lung adenocarcinoma were included in analysis from TCGA dataset. LILRB2 expression was found to have significant negative correlation with CD8+ T cell infiltration (P = 0.0012), and positive correlation with CD4+ T cell infiltration (P < 0.001). There were also significant positive correlations between LILRB2 expression and Treg (P = 0.0083), cancer associated fibroblast (P < 0.001), monocyte (P < 0.001), M2 macrophage (P < 0.001) infiltration, which was regarded as the marker of immunosuppressive microenvironment. Notably, there were also significant association between the expression of LILRB2 and PD-1 (P < 0.001) and PD-L1(P < 0.001). In terms of survival analysis, high level of Treg (HR = 0.86, P = 0.03) and M2 macrophage (HR = 0.84, P = 0.017) infiltration was associated with poor prognosis of patients with lung adenocarcinoma. However, the level of CD8+T cell (HR = 0.93, P = 0.298), CD4+ T cell (HR = 0.933, P = 0.321), and LILRB2 expression (P = 0.56) was not associated with the survival of patient with lung adenocarcinoma. Conclusions: The overexpression of LILRB2 is significantly correlated with immunosuppressive immune infiltration and microenvironment in lung adenocarcinoma and might be the potential predictive biomarkers for the PD-1/PD-L1 inhibitors.
Predictors of early hospice or death in patients with inoperable lung cancer treated with curative intent.
Authors: Laucis Anna Mary Brown , Hochstedler Kimberly A. , Boike Thomas Pence , Movsas Benjamin , Stevens Craig William , Kestin Larry Llyn , Dominello Michael M. , Wilkie Joel , Grills Inga S. , Matuszak Martha , Hayman James , Paximadis Peter Alexander , Schipper Matthew J. , Jolly Shruti ,   on behalf of the Michigan Radiation Oncology Quality Consortium
Published: June 2021

e20525 Background: Treatment for inoperable stage II-III non-small cell lung cancer (NSCLC) involves aggressive chemo-radiotherapy (CRT). While outcomes have improved with immunotherapy, some patients transition to hospice or die early in their treatment course. To help identify these patients, we developed a predictive model for early poor outcomes in NSCLC patients treated with curative intent. Methods: In a statewide consortium involving 27 sites, information was collected prospectively on stage II-III NSCLC patients who received curative CRT from April 2012 to November 2019. We defined an early poor outcome as termination of treatment due to hospice enrollment or death within 5 months of initiating radiation therapy. Potential predictors included clinical characteristics and patient reported outcomes (PROs) from validated questionnaires. Logistic regression models were used to assess potential predictors and build predictive models. Multiple imputation was used to handle missing data. We used Lasso regularized logistic regression to build a predictive model with multiple predictor variables. Results: Of the total of 2267 included patients, 128 patients discontinued treatment early due to hospice enrollment or death. The mean age of the 128 patients was 71 years old (range 48-91) and 59% received concurrent chemotherapy. Significant uni-variable predictors of early hospice or death were advanced age, worse ECOG performance status, high PTV volume, short distance to normal tissue critical structures, high mean heart dose, uninsured status, lower scores on the Functional and Physical Well-Being scale and the Lung Cancer Symptoms sub-scale of the FACT-L quality of life instrument, as well as higher levels of patient-reported lack of energy, cough, and shortness of breath. The best predictive model included age, ECOG performance status, PTV volume, mean heart dose, patient insurance status, and patient-reported lack of energy and cough. The pooled estimate of area under the curve (AUC) for this multivariable model was 0.71, with a negative predictive value of 95%, specificity of 97%, positive predictive value of 23%, and sensitivity of 16% at a predicted risk threshold of 20%. Conclusions: Our models identified a combination of clinical variables and PROs that may help identify individuals with inoperable NSCLC undergoing curative intent chemo-radiotherapy who are at a high risk of early hospice enrollment or death. These preliminary results are encouraging and warrant further evaluation in a larger cohort of patients.