bluuebunny/crossref_metadata_2025_split huggingface dataset:
Off study utilization of an unpublished trial regimen: A real-world analysis of GOG258-eligible cohorts.
Authors: Lee Sarah S. , Weil Christopher R. , Boyd Leslie R. , DeCesaris Cristina , Gaffney David K. , Suneja Gita 
Published: June 2022

e18763 Background: Practice patterns in the management of advanced endometrial cancer are widely variable and treatment paradigms are rapidly changing given the evolving clinical trial landscape. Prior studies have demonstrated “medical reversals” where clinicians favor or utilize the experimental approach only to find inferiority on publication of results. The objective of this study was to examine the utilization of the GOG 258 arms-- (adjuvant chemotherapy (CT) vs chemoradiotherapy (CRT)-- for patients with advanced or high-risk endometrial cancer. Methods: Patients 18 years or older who underwent staging surgery with stage III/IVA endometrial carcinoma of any histology or stage I/II clear cell or serous histologies with positive washings diagnosed between 2004 and 2018 were identified in the National Cancer Database. Utilization of adjuvant CT and CRT were examined in the pre-GOG 258 era (before 2009), during GOG 258 enrollment (2010-2017), and after publication of results (2018). Two-sided Cochrane-Armitage test assessed trends over time. T-test and chi-square tests assessed differences in groups receiving CT alone vs CRT. Multivariable logistic regression assessed factors associated with receipt of CRT. Propensity score matching accounted for baseline differences in groups receiving CT vs CRT. Results: 40,028 patients were included. 16,342 (41%) received adjuvant CT and 23,686 (59%) received adjuvant CRT. The majority of patients (39,185, 98%) were advanced stage and 19,616 (49%) were endometrioid histology. 90% of patients receiving both CT and CRT received multiagent therapy. Utilization of CRT was 54% before GOG 258 opening, 60% during GOG 258 enrollment, and 67% after publication of results (p < 0.001). Factors associated with receipt of CT alone were age greater than 70 (adjusted odds ratio [aOR] 0.68, 95% confidence interval [CI] 0.46-0.99), non-Hispanic Black race (aOR 0.84, CI 0.77-0.92), serous and clear cell histologies (aOR 0.68, CI 0.59-0.77; aOR 0.74, CI 0.57-0.95), living greater than 50 miles from treatment facility (aOR 0.84, CI 0.77-0.92), and receiving care in the Midwest, South, and West regions (aOR 0.84, CI 0.78-0.90; aOR 0.69, CI 0.64-0.76; aOR 0.72, CI 0.66-0.78). Compared to an academic medical center, receiving care at a comprehensive community cancer center was associated with receipt of CRT (aOR 1.2, CI 1.2-1.3). Compared to pre-GOG 258 opening in 2009, patients were more likely to receive CRT during GOG 258 enrollment (aOR 1.2, CI 1.1-1.3) and immediately after results announcement in 2018 (aOR 1.7, CI 1.5-1.8), despite results showing that CRT was not associated with longer relapse-free or overall survival. Conclusions: For patients with advanced endometrial cancer, there was significant use of both study arms with increases in CRT use during the study enrollment period and immediately after reporting of GOG 258 results, despite lack of benefit in the CRT arm.
Real-world data comparing third and subsequent line regimens for treatment of metastatic triple-negative breast cancer in the United States.
Authors: Aran Dvir , Klein-Brill Avital , Fisch Michael Jordan , Amar-Farkash Shlomit 
Published: June 2022

e18765 Background: Eribulin is a commonly prescribed regimen for metastatic triple negative breast cancer (mTNBC) patients pre-treated with one or more chemotherapy regimens, although no clear survival benefit has been shown when compared to treatment of physician's choice (TPC) [1]. Here, using real-world oncology data we compare the impact of treatment with Eribulin vs. other common chemotherapies as third and subsequent lines of therapy on overall survival and post-treatment hospitalizations. Methods: We performed a retrospective cohort study of third and subsequent lines (3L+) treatment of patients with mTNBC between 1/2016 and 6/2021 using administrative claims data from the Anthem Cancer Care Quality Program. Real-world overall survival (rwOS) was defined as time from diagnosis to death. Real-world overall survival (rwOS) was defined as time from diagnosis to death. A Cox model with inverse probability of treatment weighting was used to adjust for age, ECOG, socioeconomic status, comorbidity, and liver and bone metastatic sites. Median rwOS was estimated using the weighted Kaplan-Meier method. Adjusted hazard ratios (aHR) were estimated using weighted Cox proportional hazards models. Results: We identified 210 (52%) individuals with mTNBC who received Eribulin (E) for 3L+, compared to 189 patients treated with other chemotherapies (O), which include carboplatin+gemcitabine, nab-paclitaxel, vinorelbine, paclitaxel, carboplatin and nab-paclitaxel+atezolizumab, ordered by frequency. We found no significant difference in any of the demographic and clinical features tested between the groups (Table). Median rwOS in the E group was 6.4 months, compared to 7.6 months in the O group (p-value = 0.4). In adjusted survival analyses to known confounders, E showed no significant difference in mortality (aHR: 1.09, 95% Confidence Interval [CI]: 0.87-1.37, p-value = 0.46). Furthermore, we found no significant difference in hospitalizations following the treatment between the E to the O group (36% vs. 39%, p-value = 0.6), length of stay (7 vs. 8 days, p-value = 0.8) and classes of associated severe adverse events. Conclusions: Our analysis of real-world oncology data aligns with National Institute for Health and Care Excellence (NICE) recent recommendation in showing no survival benefit or reduction in post-treatment adverse events when treating with Eribulin at 3L+ in metastatic TNBC patients.[Table: see text]
Smoking and COVID-19 in patients with cancer: Novel analysis from CCC19 registry.
Authors: Kulkarni Amit , Hennessy Cassandra , Wilson Grace , Ramesh Vidhyalakshmi , Hwang Clara , Awosika Joy , Bakouny Ziad , Vilar-Compte Diana , Khan Hina , McKay Rana R. , Jani Chinmay , Puc Matthew , Kasi Anup , Berg Stephanie A. , Castillo Dan Ran , Hayes-Lattin Brandon M. , Hosmer Wylie , Flora Daniel Blake , Duma Narjust ,   COVID-19 and Cancer Consortium
Published: June 2022

e18766 Background: Patients (pts) with thoracic cancers have a high rate of hospitalization and death from COVID-19. Smoking has been associated with increased risk for severe COVID-19. However, there is limited data evaluating the impact of smoking recency on COVID-19 severity in pts with cancer. We aimed to characterize the clinical outcomes of COVID-19 based on the recency of smoking in pts with thoracic cancers (TC) and all other cancers (OC). Methods: Adult pts with cancer and lab-confirmed SARS-CoV-2 and smoking history recorded in the CCC19 registry (NCT0435470) were included. Pts were stratified by cancer type (TC or OC) and further stratified into subgroups based on the recency of smoking cessation: current smoker; former smokers who quit < 1 yr. ago; 1-5 yr. ago; 6-10 yr. ago; quit > 10 yr. ago; and never smoker. 30-day all-cause mortality was the primary endpoint. Secondary endpoints were any hospitalization; hospitalization with supplemental O2; ICU admission; and mechanical ventilation. Results: From January 2020 to December 2021, 752 pts from TC group and 8,291 pts from OC group met the inclusion criteria. 78% of patients in TC group ever smoked compared to 36% patients in the OC group. In both groups, the majority of never-smokers were females (70% and 60% in TC and OC respectively). The burden of smoking and the rate of pulmonary comorbidities (PC) was higher in the TC group (PC 22-69%) compared to OC group (PC 12-26%) across all smoking strata. Overall, 30-day all-cause mortality was 21% and 11% in pts with TC and OC respectively. Former smokers who quit < 1 year ago in TC group had the highest rate of mortality and severe COVID-19 outcomes. However, in the OC group, there was no consistent trend of higher mortality or severe COVID-19 outcomes in specific subgroups based on smoking recency. Conclusions: To our knowledge this is the largest study evaluating the effect of granular phenotypes of smoking recency on COVID-19 outcomes in pts with cancer. Recent smokers who quit < 1 year ago in TC group had the highest rate of mortality and severe COVID-19. Further analysis exploring the factors (e.g., smoking pack years) associated with severe outcomes in this subgroup is planned.[Table: see text]
A comparison of dosimetry and clinical outcomes in patients receiving photon external beam therapy to the pelvis: A two-year experience with 6MV and 10MV photon energies in cervical cancer patients at Parirenyatwa Radiotherapy Centre in Harare, Zimbabwe.
Authors: Banda Chimwemwe Moses , Ndlovu Ntokozo , Nyamhunga Albert 
Published: June 2022

e18768 Background: Radiotherapy efficacy depends on the ability of the treatment machine to deliver optimal radiation dose to target volume while sparing normal tissue using different techniques. The photon energy determines penetrative power. Higher photon energies are generally preferred over low photon energies when treating deep tumours using 3-dimensional conformal radiotherapy (3DCRT). In most low income settings, availability of higher energies (≥10MV) is limited. Elsewhere protocols do not recommend use of lower energies for deep pelvic tumours. There is paucity of data comparing 10MV and 6MV photon energy plans and outcomes for treatment of pelvic tumours with 3DCRT. This study aimed to compare dosimetric and clinical tumour outcomes between the two photon energies which are available in our setting when treating locally advanced cervical cancer (LACC). Methods: We retrospectively analysed medical records for LACC patients who received definitive concurrent chemoradiotherapy (CCRT) at Parirenyatwa Group of Hospitals Radiotherapy Centre for the period between 1st January 2017 and 31st December 2018. Patient’s treatment plans were stratified into two arms according to the photon energies used (10MV and 6MV) and their respective dosimetric and clinical tumour outcomes at three months post-treatment were compared. Results: A total 875 cervical cancer patients were seen during the study period, of these 82 met the inclusion criteria and were evaluated. Out of these, 20(24.4%) and 62(75.6%) patients were planned and/or treated with 10MV and 6MV photon energy respectively. The differences in minimum doses to the planned target volume and dose homogeneity index between the two photon energies were statistically significant (p-values 0.027 and 0.028 respectively), whereas the other dosimetric parameters (maximum & average doses to the planned target volume, conformity index and maximum doses to rectum, bladder, femoral heads and bowel) were not statistically significant (p-values of 0.245, 0.309, 0.130, 0.19, 0.35 and 0.42, and 0.16 respectively). Complete clinical tumour response at 3 months post treatment was 95% in the 10 MV arm compared to 91% in the 6 MV arm. Conclusions: This study showed that the dosimetric and clinical tumour outcomes in LACC patients receiving 3DCRT definitive CCRT using 10MV or 6MV photon energy in our setting are comparable. Follow-up prospective studies to further characterise the application of these photon energies in resource constrained settings is recommended.
Methods used to generate safety-related evidence in real-world oncology settings: A systematic literature review.
Authors: Henderson Mackenzie , Cueto Jenilee , Yalamanchili Priyanka , Salas Maribel 
Published: June 2022

e18769 Background: With the increasing availability of real-world data (RWD) as a valuable healthcare data source, there have been large shifts in how a drug’s properties can be evaluated over its life cycle. RWD can be used for many evidence generation purposes, including the evaluation of a drug’s safety in real-world settings outside of clinical trials. Traditional methods (e.g., cohort and case-control studies) are often used to analyze RWD, but novel methods have emerged as the field advances with access to more diverse data sources. The extent to which these newer methods are being used is unclear. The aim of this systematic review is to identify methods that have been used in recent years to generate safety-related evidence in real-world oncology settings. Methods: A search of literature published between 1/1/2016-8/10/2021 (Embase, Ovid) was performed to identify studies describing methods used to generate evidence related to the real-world safety of oncology products. Each article was independently screened by two researchers in two levels (title/abstract and full text screening). Data extracted included, but was not limited to, study design, cancer type, data source, and statistical methods. Results: Out of 845 publications identified, 44 were included for review (742 excluded after level 1 screening; 59 excluded after level 2 screening). The most common method used was the retrospective cohort study (n = 26), followed by prospective cohort study (n = 8), literature review (n = 4), cross-sectional study (n = 3), artificial intelligence (AI) methods (n = 3), data mining analysis (n = 2), case-series, and case-control study (n = 1 each). Some publications used multiple methods. While traditional methods (e.g., cohort study, literature review) were the most common throughout the search period, newer methods (e.g., AI methods) were identified in the latter part of the search period (2019-2020). The majority of studies that used traditional methods relied on medical records or claims data (e.g., Optum), which often provided structured RWD to evaluate physician-documented drug safety data. In contrast, articles that used newer methods like AI analyzed large amounts of patient-reported data (e.g., chatbot conversations; social networks), which allowed researchers to evaluate patients’ own experiences with drug safety. Conclusions: The most common evidence generation methods identified involved traditional methods, but novel methods were also identified, especially in recent years. This indicates a trend towards increased use of innovative methods like AI that allow for the analysis of data in ways not possible before. Taken together with more traditional methods and data sources, these findings can provide clinicians with a more comprehensive and patient-focused understanding of drug safety, which will ultimately improve patient care.
Breast density changes over time: Frequency, patterns, and practice implications.
Authors: Maloney Caitlin , Paul Shirlene , Lieberenz Jordan , Levy Mia Alyce , Stempel Lisa , Alvarado Rosalinda 
Published: June 2022

e18772 Background: Dense breast tissue is known to obscure malignancy on mammography and is considered an independent risk factor for breast cancer. Because of its clinical significance, breast density has been incorporated into cancer risk assessment tools, supplemental screening recommendations, and patient notification laws. Changes in density—whether due to intrinsic changes in breast tissue over time or to inter-radiologist variability in interpreting mammographic results—can therefore have significant implications for patients. The purpose of this study was to quantify longitudinal patterns of breast density change. Methods: This retrospective cohort study tracked breast density changes among 37,156 patients who received multiple mammograms at a large academic medical center between October 1, 2015 and June 29, 2021. Breast Imaging-Reporting and Data System (BI-RADS) density categories A (least dense) through D (most dense), visually determined by radiologists at the time of screening, were abstracted from electronic medical records and dichotomized into one of two density statuses: non-dense (categories A and B) and dense (categories C and D). A sequence analysis of longitudinal changes between the two density statuses was performed using SQL. Results: The majority (91.3%, n = 33,920) of patients maintained the same density status (dense or non-dense) throughout the six-year study period, while 8.7% of participants (n = 3,236) experienced between one and six density status changes. Among patients who experienced any density status change, the vast majority (96.7%, n = 3,131) moved exclusively between BI-RADS categories B and C, the intermediate density categories (Table). Frequency of density status change was positively correlated with average number of mammograms performed per patient. Conclusions: Although most patients maintain a consistent breast density status, some will experience multiple status changes even over this relatively short timeframe (< 6 years), with more frequent changes being associated with more frequent mammograms. The overwhelming majority of patients whose density status changed moved exclusively between BI-RADS categories B and C, suggesting a role for inter-radiologist variability in visual assessments of intermediate-density tissue. These findings have implications for how density status changes are incorporated into patient education, risk assessment, and supplemental screening recommendations.[Table: see text]
Evolution of biomarker testing in advanced non-small cell lung cancer (aNSCLC) and metastatic breast cancer (mBC) in U.S. community practices.
Authors: Schwartzberg Lee S. , Yu Elaine , Meyer Craig S. , Shah Anuj , Price Richard , Szado Tania , Vaena Daniel A. , Daniel Davey B. , Slater Dennis , Staszewski Harry , Fang Bruno , Seneviratne Lasika , Ma Esprit 
Published: June 2022

e18778 Background: Biomarker testing has advanced from single-gene to NGS. This study examined aNSCLC and mBC biomarker testing ≤ 90d of advanced (adv) or metastatic (met) diagnosis (Dx) and treatment (tx) patterns at US practices. Methods: A retrospective observational study used Flatiron Health electronic health-record-derived de-identified database at OneOncology (OO) community and non-OO Flatiron Health nationwide (NAT) sites (̃90% community, ̃10% academic). Patients (Pts) ≥ 18y, with Dx of aNSCLC or mBC from 1/1/18 - 4/30/21, with ≥ 1 visit ≤ 90d after adv/met Dx and ≥ 90d follow-up were evaluated. Descriptive analyses and logistic regression were used. Results: A total of 16,882 pts with aNSCLC (2366 OO; 14,516 NAT), and 6500 pts with mBC (1026 OO; 5474 NAT) were included. Overall testing was high and stable (OO: 85% aNSCLC, 98% mBC; NAT: 84%, 97%) with higher NGS testing at OO (58% aNSCLC; 28% mBC) vs NAT (49%; 16%) (Table), which reflected more pts with aNSCLC tested for all 6 mutations (ALK, BRAF, KRAS, ROS-1, EGFR, PD-L1; 54% OO vs 50% NAT, p<0.001) and more pts with mBC tested for PIK3CA (27% OO vs 16% NAT, p<0.001). In aNSCLC, NGS testing increased similarly for OO and NAT over time (p>0.05); mBC NGS testing increased faster at NAT vs OO (p<0.05). Of pts tested and treated, 16% aNSCLC (1945 OO; 11,376 NAT) and < 3% mBC (14 OO; 108 NAT) received tx before test results were available. For pts with aNSCLC with ≥ 1 actionable mutation (ALK, BRAF, ROS-1, EGFR), 18% OO and 22% NAT had tx before test results. Cancer immunotherapy plus chemotherapy was the most common tx (36 % OO vs 40 % NAT); after test results, 33% vs 56% OO and 45% vs 44% NAT pts stayed on tx vs switched to targeted tx. For pts with aNSCLC with ≥ 1 aforementioned actionable mutations who waited until test results were available, 65% received targeted tx at OO and NAT. Conclusions: Biomarker testing has become standard of care in aNSCLC and mBC in US community settings. NGS rates increased over time and were higher at OO vs NAT. Differences in pts treated before test results reflects the need to wait for NGS results to inform initial tx in aNSCLC vs non-NGS results for mBC. This study shows NGS testing in US community practices has increased since 2018, particularly in mBC, but opportunities remain to optimize NGS results into tx decisions.[Table: see text]
Defendor: Real-world evidence of primary prolonged G-CSF prophylaxis by empegfilgrastim for relative dose intensity compliance in patients with solid tumors—The primary analysis.
Authors: Snegovoy Anton , Dergunov Alexander , Tatyanenko Anna , Yakuba Darya , Elkova Viktoriya , Shalina Anna , Komoza Yulia , Dmitrochenko Marina , Soroka Svetlana , Shegurova Margarita , Chapko Yana , Dmitriev Vadim , Timin Vladimir , Rossokha Elena , Gronskaya Yulia , Kononenko Inessa , Sorokina Irina 
Published: June 2022

e18788 Background: Maintaining relative dose intensity (RDI) of chemotherapy is important to ensure optimal patient outcomes in a variety of solid cancers. RDI < 85% significantly decrease therapy efficiency (including overall survival) in almost solid tumors (ST). Chemotherapy-induced neutropenia (CIN) is the most common adverse event (AE) leading to low RDI. Proper administration of primary G-CSF prophylaxis (PP) allows to achieve optimal therapy efficiency. There are several trials and meta-analyses have shown a superior efficiency prolonged G-CSF vs short G-CSF. This multicenter prospective observational post-registration study of prolonged G-CSF empegfilgrastim (Extimia) was designed to evaluate the RDI of the cytotoxic therapy course under PP by empegfilgrastim in patients (pts) with ST receiving myelosuppressive therapy in the routine clinical practice. Methods: 2000 pts with ST receiving cytotoxic therapy (4-8 cycles per course are allowed) under PP with empegfilgrastim by investigator choice in the routine clinical practice. RDI of therapy course was primary endpoint and presented here for pts who completed the planned regimen. For each agent, both the planned and actual dose intensity were calculated by dividing the total cumulative dose by treatment duration in days. RDI was calculated for each single agent in chemotherapy-based (CTb) regimen and for CTb regimen in total. These descriptive analyses and RDI calculations were performed for the whole CT based regimen (chemotherapeutic agents, molecular target agents, monoclonal antibodies). Funded by JSC Biocad; Defendor ClinicalTrials.gov No NCT04811443. Results: At the data cut-off 1074 pts from 31 Russian sites underwent ≥ one cycle of CTb regimens combined with empegfilgrastim. Distribution of all-cancer types was in line with epidemiology data in Russia. 526 pts completed the planned CT course. 352 (66,9%) of them have at least onе of FN risk factor. RDI≥85% were achieved in 492 (93,5%) pts. RDI by key nosology is presented in Tab.1. 118 (22,4%) cases of interval prolongation and/or dose reduction was registered. The main reasons of RDI decrease were personal pts’s issues 69 (13,1%), COVID-19 pandemic 26 (4,9%), holidays 9 (1,7%) and others. Neutropenia was in 6 (1,1%) cases as a reason of RDI decrease. Treatment-related AEs of grade 1-2 occurred 12 (2,3%) pts (back pain, ossalgia, myalgia). Conclusions: Thus, PP with prolonged G-CSF empefilgrastim allows effectively maintain RDI in different nosology and treatment groups in pts with ST in the routine clinical practice.[Table: see text]