bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation therapy and associated cardiovascular outcomes in patients with Hodgkin’s lymphoma.
Authors: Dalal Shivani , Patel Krunalkumar , Hussein Atif Mahmoud , Gattas Boula , Patel Akash , Dalal Misha , Nguyen Thanh , Patel Umang 
Published: June 2022

e19528 Background: Hodgkin’s lymphoma (HL) is a lymphoid neoplasm, with lymphadenopathy with constitutional symptoms as presenting manifestations. The treatment is guided by the clinical stage of disease, and is curable in about 75% of the patients. Advances in cancer therapeutics have improved survival rates, however treatment-related toxicities have become a competing cause of late mortality. Radiation therapy (RT) and chemotherapy have historically been the pillars of curative treatments for HL. RT to the thorax is associated with substantial risk for the development of cardiovascular (CV) disease including pericardial disease, coronary artery disease, valvular disease, conduction disease, cardiomyopathy. The true incidence of radiation-related cardiovascular disease remains uncertain due to lack of large multi-centre studies with a sufficient duration of CV follow-up. Through this study we aim to determine the CV co-morbidities and outcomes of patients with HL treated with and without RT. Methods: We identified hospitalized adult patients with HL and divided them into patients with and without history of radiation therapy from October 2015 to December 2018 from the National Inpatient Sample Database using ICD 10 codes. We further determined demographics, baseline characteristics, associated CV co-morbidities, mortality, length of stay and hospitalization costs among patients with HL with and without history of RT. SAS 9.4 software was used for statistical analysis. Results: We captured 86,325 patients hospitalized with HL during the study period out of which 11,030 patients had history of RT. The patient cohort with RT was noted to have higher prevalence of hypertension (40.7 vs 37.1%), heart failure with reduced ejection fraction (9.2 vs 6.4%), heart failure with preserved ejection fraction (9.2 vs 5.9%), coronary artery disease (33.6 vs 20.3%), atrial fibrillation (19.2 vs 14%), aortic valve disease (10.1 vs 3.8%), mitral valve disease(5.6 vs 2.7%), pulmonary hypertension (9.6 vs 4.6%), and pleural effusion(9.7 vs 6.8%) as compared to patients without history of RT. The study did not show any statistically significant difference in length of stay or in-hospital mortality in the two groups. Conclusions: This study revealed significantly higher prevalence of multiple CV co-morbidities among HL survivors treated with RT. CV disease is now the most common non malignancy related cause of death in radiation-treated cancer survivors. Awareness and early identification of cardiac complications is crucial survivors. There are currently no consensus guidelines to dictate the optimal surveillance of recipients of thoracic radiation. Therefore through this study we aim to shine light on the importance of early surveillance and collaboration between oncologists and cardiologists in the management of the cancer survivors with history of RT.
Predictors of secondary lung cancer among Hodgkin lymphoma survivors: A nationwide analysis.
Authors: Alnimer Yanal Mufeed , Mustafa Ali Moaath Khader 
Published: June 2022

e19529 Background: There is insufficient data regarding the incidence rate of secondary lung cancer among Hodgkin lymphoma survivors and the predisposing factors. Methods: We analyzed the data from the cohort of subjects who had Hodgkin Lymphoma between 1973 and 2015 using the Surveillance Epidemiology and End Results database (SEER). Data on patient's age, gender, year of diagnosis with Hodgkin lymphoma, Ann-Arbor stage, Histology, racial groups, date of last follow-up, date of death, and treatment modalities were collected. Results: We identified a total of 56,856 subjects with Hodgkin lymphoma; of those, 862 had secondary lung cancer, with an incidence rate of 157 (95%CI: 147-168) per 100,000 person-years. The median overall survival from time of Hodgkin Lymphoma diagnosis for those with secondary lung cancer was 12.1 years (95%CI: 10.7-13) compared to 27.1 years (95%CI: 26.5-27.6) for those who did not develop lung cancer. After propensity score weighting, radiation therapy was associated with a higher risk of secondary lung cancer (HR: 1.23, 95%CI: 1.002-1.55). Older age at the time of Hodgkin lymphoma diagnosis and male gender were associated with higher risk, with an HR of 1.07 (95%CI 1.062-1.073) and an HR of 1.602 (95%CI 1.33-1.94), respectively. Furthermore, chemotherapy increases the risk only among older age groups. Conclusions: Older age at the time of Hodgkin Lymphoma diagnosis, male gender, radiation therapy and chemotherapy only among older age groups were associated with higher risk for secondary lung cancer, with 50% of the cases occurring within 9.1 years following Hodgkin lymphoma diagnosis.[Table: see text]
Neutropenia and neutropenic fever with polatuzumab vedotin for diffuse large B-cell lymphoma: Meta-analysis of randomized clinical trials.
Authors: Gupta Varsha , Singh Vinit , Khalid Farhan , Eltoukhy Hussam , Meghal Trishala 
Published: June 2022

e19576 Background: Polatuzumab vedotin (POLA) is an antibody–drug conjugate composed of an anti-CD79b monoclonal antibody conjugated by a protease-cleavable linker to monomethyl auristatin E, a microtubule inhibitor. POLA has shown efficacy in patients with relapsed or refractory Diffuse large B-Cell lymphoma (DLBCL) and recently shown better progression free survival in previously untreated DLBCL as well. We conducted a meta-analysis of randomized controlled trials (RCTs) to determine the relative risk of neutropenia and febrile neutropenia associated with use of POLA regimens for DLBCL. Methods: We conducted a systematic search at PUBMED, EMBASE, and meeting abstracts as per PRISMA guidelines from 2010 until December 2021. Randomized controlled trial utilizing POLA for DLBCL were included. We used the Mantel-Haenszel (MH) method utilizing random effects model to calculate pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value. All statistical analyses were performed with Review Manager Version 5.4. Results: A total of 1073 patients from 3 RCT (1 Phase III and 2 Phase II Studies) were included in this study. The study arm used POLA-R-CHP (Rituximab, Cyclophosphamide, Doxorubicin, Prednisone), POLA-Rituximab, and POLA-BR (Bendamustine-Rituximab). The control arm used R-CHOP, Pinatuzumab-R, and BR respectively The overall incidence of neutropenia was 31.54% in POLA Group vs 32.94% in control group with RR 0.99 (95% CI: 0.69 – 1.42, P=0.97, I2=16%) whereas grade 3-4 neutropenia incidence was 29.24 vs 30.82 with RR 0.95 (95% CI: 0.79 – 1.16, P=0.65, I2=2%). The overall febrile neutropenia incidence was 12.87% in Polatuzumab group vs 7.90% in the control group with RR 1.62 (95% CI: 1.12 – 2.35, P = 0.01, I2=0%). Conclusions: Our study demonstrated that there was no statistical difference in risk ratio of any grade neutropenia (including grade 3-4) in both the arms. However, there was significantly increased risk of febrile neutropenia among patients who received Polatuzumab vedotin based treatment compared to those who did not. Further studies and long term follow up are necessary to define the actual relation and definitive incidence.[Table: see text]
Geographic disparity between patients with multiple myeloma (non-Whites and Whites).
Authors: Cheung Christian S. , Sweeney Nathan W. , Molina Thomas H. , Ahlstrom Jennifer M. 
Published: June 2022

e20003 Background: People that live in rural areas experience significant health disparities from higher incidences of disease and disability, increased mortality rates, and lower life expectancies. Rural risk factors for health disparities include geographic isolation, lower socioeconomic status, limited access to healthcare specialists and sub-specialists, and limited job opportunities. Interestingly, we often see other, non-white, races experience delays in care, are under-treated, and lack of access to MM specialists. We, therefore, investigated whether there was a relationship between race and where one lives geographically. Methods: Validated real-world (RW) MM patient data was collected through HealthTree Cure Hub for Multiple Myeloma (healthtree.org). We examined the patient’s race which was either Caucasian American (White) or any other race (Black American, Asian, American Indian, East Indian, Middle Eastern, or Native Hawaiian) which was categorized as “non-White” and where they lived geographically (Rural, Urbanized Cluster, or Urban Areas). The association between race and geographic classification was compared by using a chi-squared test. Results: In this retrospective analysis of 2,687 MM patients, we compared the geographical classification of Whites (n = 2403) and non-Whites (n = 284). Our analysis revealed a significant association between the two groups and where they lived with a chi-square value of 20.455 (2, n = 2,687, p < 0.001). We found that Whites are 1.9 times more likely to live in urbanized cluster areas and 2.7 times more likely to live in a rural area compared to non-Whites. Conclusions: The results of this RW analysis identified a disparity among races and where one lives geographically. While there is strong evidence of health disparities our findings revealed that where one lives geographically is not a probable reason why non-Whites experience delays in care, are under-treated, or lack access to MM specialists.
Smoldering multiple myeloma progression to multiple myeloma in a community-based population.
Authors: Fatoki Raleigh Ayoolu , Carpenter Diane M. , Ramalingam Nirmala D. , Khan Adnan Ahmed , Nair Bijay P. , Stevenson Ryan Lloyd , Green Michael M. , Lo Joan C. , Baer David M. 
Published: June 2022

e20015 Background: Few studies have characterized patients with smoldering multiple myeloma (SMM) in ethnically diverse settings and data regarding progression to multiple myeloma (MM) in real-world clinical populations is limited. Using data from a large healthcare system, we examined a contemporary cohort of adults with confirmed SMM and their progression to MM. Methods: We conducted a retrospective cohort study of SMM cases from 2010-2017 in Kaiser Permanente Northern California (KPNC). We used the KPNC SEER-based Cancer Registry to identify potential SMM cases by ascertaining MM cases with either: 1) “asymptomatic, evolving, or smoldering myeloma” status in the Cancer Registry or 2) mention of “smoldering” in clinical records. Chart review was conducted for potential SMM cases and confirmed SMM status was assigned using the 2014 IMWG criteria. SMM cases were followed for progression to MM and myeloma-directed therapy, excluding those with KPNC membership <1 year after diagnosis. Time to MM progression (or treatment) was examined. SMM cases were classified during follow-up as: a) SMM, no progression to MM (and no receipt of myeloma-directed therapy); b) SMM, progression to MM (and receipt of myeloma-directed therapy); and c) SMM, receipt of myeloma-directed therapy without frank progression to MM (follow-up was censored at treatment). Results: During 2010-2017, we identified 152 adults with confirmed SMM. The median age at diagnosis was 71 years (IQR, 62-78), 56% were male, and 55% were non-Hispanic White, 17% Black, 9% Hispanic, and 18% Asian. During follow-up, 28% of patients progressed to MM, with a median time to progression of 1.2 years (IQR 0.8-2.0). Over half (58%) did not progress during a median follow-up time of 3.4 years, and an additional 14% received treatment before a MM-defining event. Progression data by demographic group is shown in Table. Conclusions: This is one of the first studies to examine SMM progression in an ethnically diverse cohort using the 2014 IMWG criteria. Although follow-up time was limited, we found that over half of the identified SMM cases did not progress to MM. However, patients who did progress to MM generally required treatment within 2 years of SMM diagnosis. These findings support efforts to identify high-risk patients with SMM who may benefit from early initiation of therapy. [Table: see text]
Using electronic health records to derive a synthetic control arm for a historical trial on relapsed/refractory multiple myeloma.
Authors: Bisquera Alessandra , Wallis Jamie , Valencia Ray , Ruau David , Scott-Ram Nicholas , Carpenter Lewis 
Published: June 2022

e20025 Background: It is increasingly challenging and ethically questionable to recruit patients on control arms when a vast body of information is readily available through electronic health records (EHR). Synthetic Control Arms (SCA) may reduce the time and cost of running a trial, and ultimately alleviate patient burden. This study explores the potential of SCAs derived from EHR to provide additional support for trials investigating treatment efficacy in multiple myeloma (MM). Methods: De-identified EHR from a UK NHS trust were matched with patients from a historical, Phase III randomised control trial investigating the efficacy of elotuzumab therapy in combination with lenalidomide and low-dose dexamethasone in relapsed/refractory MM (ClinicalTrials.gov Identifier: NCT01239797). Trial specific eligibility criteria were applied to the EHR dataset to derive 94 patients for the SCA. The primary outcome was progression free survival (PFS), as defined by the International Myeloma Working Group based on relative and absolute changes in serum M protein or kappa/lambda free light chain assay. The observation period was defined as time from randomisation (Trial) or treatment initiation (SCA) to death or disease progression. Results: In the SCA, the median age was 72 years [range 41, 93], 44% female, 76% white ethnicity, between 1 to 3 prior therapies, and between 0 to 6.3 years since diagnosis. This is in comparison to the trial control arm (n = 325) with a median age of 66 years [range 38, 91], 41% female, 86% white ethnicity, 1 to 4 prior therapies, and 0 to 16.2 years since diagnosis. Median PFS in the SCA was 14.4 months (95% Confidence Interval (CI) 9.5, 22.2), compared to 14.9 months (95% CI 12.1, 17.2) in the trial control arm. The hazards of progression or death in the trial treatment arm (when compared to trial control) was 0.70 (95% CI 0.57, 0.85) and 0.71 (95% CI 0.54, 0.95) when compared to the SCA. Additional sensitivity analysis using Multiple Imputation of missing ECOG values in the SCA yielded similar results, with a median PFS of 16.5 months (95% CI 10.4, 24.0) and hazards that is 0.77 (95% CI 0.57, 1.05) lower in the treatment arm. Conclusions: These results show that SCA can generate valuable additional evidence of efficacy supporting regulatory submission with considerable benefits in term of budget and time. Future work on SCAs aim to further refine the precision of estimates by applying the best performing confounder adjustment techniques.
A systematic review on smoldering multiple myeloma: Whether treatment is beneficial.
Authors: Sathe Sanjivani , Selene Insija Ilyas , Jose Jemin , Adhikari Biplov , Waqar Syed Hamza Bin , Shah Zunairah , Haider Mobeen Zaka , Anwer Faiz 
Published: June 2022

e20029 Background: Smoldering multiple myeloma (SMM) is an asymptomatic proliferative disorder of plasma cells. There are multiple early intervention strategies investigated in the last ten years, including single v/s combination therapy, which can either delay progression or be used as an aggressive therapy to cure SMM. This study aims to summarize the reported outcomes of interventions in SMM within the past decade. Methods: We performed a literature search following PRISMA guidelines and used the following bibliographic databases: PUBMED, EMBASE, Cochrane Library, Web of Science, and clinical trials.gov. A total of 1474 articles were found from the above-mentioned databases and a total of seven articles were included in the final analysis. Results: Seven clinical trials were finalized, which included 599 patients, gender was specified in five studies and constituted 51 percent female patients, and the remaining were males. The median age of patients ranges from 61 (21-89) years. In progression evaluation, four studies, 440 patients were considered. However, significant heterogeneity existed with treatments and the survival analysis hence cumulative PFS was not obtained. PFS greater than 90% was obtained in two studies; 95.5% was obtained with Carfilzomib (K), lenalidomide (R), and dexamethasone(d) regimen after a follow-up period of 31.9 months. PFS of 91% was obtained with Lenalidomide alone for a follow-up of 35 months. Three studies, including 200 patients, were evaluated for response rate. MRD negative CR of 70.4% was obtained with the use of the KRd regimen. Overall response (ORR) of intense and intermediate use of Daratumumab showed a rate of 56.7% and 53.1%, while the complete response in the respective arms was 4.9% and 9.8%. CR, stringent CR of 17.4% and 4.3% was obtained with the use of Isatuximab with Lenalidomide. Conclusions: No definite conclusion can be made due to variability in the data. However, based on the data analyzed from the seven clinical trials, we advocate for early therapeutic intervention in high-risk SMM patients. There are multiple ongoing clinical trials to answer whether we should treat SMM or not.[Table: see text]
Retrospective analysis of vaccine antibody titers in patients with different stages of monoclonal plasma cell disorders.
Authors: Taneja Alankrita , Parker Sarah , Ba Aqeel Sheeba Habeeb , Attwood Kristopher , Hillengass Jens 
Published: June 2022

e20031 Background: Infections occur with up to twofold increased risk in patients with monoclonal gammopathy of undetermined significance (MGUS) and tenfold increased risk in multiple myeloma (MM). To reduce risk, revaccination following autologous hematopoietic cell transplantation (AHCT) is recommended to restore humoral immunity. We have previously shown that vaccine titers after AHCT have prognostic significance. In the COVID era, reliable clinical data about antibody titers is relevant yet scarce. We investigated the significance of different vaccine titers in newly diagnosed patients in different stages of the disease. Methods: The study population comprised of 77 patients with MGUS, smoldering multiple myeloma (SMM) and MM who were seen at a tertiary cancer center from 2018-2022. All patients had antibody titers (B. pertussis, Diptheria, H. Influenzae B, Hepatitis, Influenza, Meningitis, Mumps, Rubeola, Rubella, Poliovirus, S. pneumoniae, Varicella Zoster and Tetanus) tested at the time of diagnosis, prior to start of treatment if indicated. Titers were interpreted in accordance with the manufacturers’ recommendations. Patient characteristics were compared using the Kruskal-Wallis and Fisher’s exact tests. Associations with % titer positivity were evaluated using the Kruskal-Wallis test. Results: There was significant difference in antibody titer positivity between the different patient groups (51.4% in MGUS, 40.5% in SMM and 34.2% in MM) (p < 0.001). There was no difference in antibody titer positivity depending on age, sex or race. Among individual pathogens, there was a significant difference between the three groups in regards to titers for Diphtheria, Mumps, Poliovirus 3, Strep pneumoniae 19, Strep pneumoniae 56 and Varicella Zoster. Conclusions: Antibody titers for vaccine preventable diseases are significantly different between patients with MGUS, SMM and MM at the time of diagnosis, with MGUS having the highest and MM having the lowest positivity. Patient related factors such as age, sex or race were not associated with antibody titer positivity. Current guidelines for revaccination are not extended to patients with MGUS and SMM and can be considered in prospective trials.[Table: see text]
Extended neoadjuvant therapy in NSCLC achieved remarkable pathological complete response (pCR) rate and prolonged disease-free survival.
Authors: Fan Zhaohui , Wang Xiaojunn , Xu Youtao , Li Si , Chen Dong-sheng , Xiao Mingzhe 
Published: June 2022

e20500 Background: Over 50% early stage NSCLC patients would suffer from recurrence and distant metastasis. Neoadjuvant TKI therapy had been explored aiming to reduce recurrence and metastasis. Erlotinib neoadjuvant therapy (NAT) significantly improved ORR, PFS and major pathologic response (MPR) rate in trial EMERGING/CTONG1103. In our hospital, some patients received extended neoadjuvant treatment because of continued lesion remission. These patients eventually received surgery when the lesions stopped remission and achieved remarkable pathologically complete remission (pCR) rate. Herein we analyzed the efficacy of extended NAT. Methods: 9 NSCLC patients who received extended neoadjuvant therapy in Department of Thoracic Surgery, Jiangsu Cancer Hospital from 2013-2020 were enrolled in this study. Extended neoadjuvant therapy was defined as duration of treatment longer than standard regimens (for TKI, longer than 42 days; for chemotherapy, longer than 2 cycles or 6 weeks). Pathological complete response, progression free survival (PFS), overall survival (OS) were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Standard statistical methods, including descriptive statistics, x2 test, two-sided 95% CI were used. Results: Up to 9 patients were enrolled in this study. There were 5 patients in TKI group, 1 (20%) was male and 4 (80%) were female. There were 4 patients in chemo group, 2 (50%) were male and 2 (50%) were female. The median age of TKI and chemotherapy groups were 59 (47-70) and 62 (30-75), respectively. The median duration of treatment (DOT) were 185 (163-248) and 82 (29-98) days, respectively. Among TKI group, 4 patients were EGFR L858R positive and 1 was ALK rearrangement positive and they all received relative TKI treatment based on genetic feature. In the TKI group, all 5 patients achieved pCR, the pCR rate was 100%. In chemotherapy group, 1 out of 4 patients achieved pCR and the other 3 achieved major pathological response (MPR). The pCR rate was 25% and MPR rate was 100%. The pCR rate of TKI group was significantly higher than chemotherapy group (100% vs 25%, p < 0.01). The pCR rate or MPR rate was higher than historical data. For instance, in trial CTONG 1103, neither TKI (Erlotininb) or chemotherapy (Gemcitabine) group achieved pCR, and the MPR rate was only 45% in TKI group and 51% in chemotherapy group. Extended NAT regimen in our study achieved much higher pCR rate (100% vs 0% for TKI and 25% vs 0% for chemotherapy) and MPR rate (100% vs 45%̃51%) than standard 42 days regimens used in CTONG-1103. Conclusions: Extended NAT resulted in better pCR rate and MPR rate than the standard 42-days duration of NAT. For patients with good response to TKI in the neoadjuvant stage, extending the duration neoadjuvant TKI treatment until lesions stopped remission might result in better pCR rate and might extend PFS and OS.