bluuebunny/crossref_metadata_2025 huggingface dataset:
Amount of cancer stem cells in tumors of patients with ovarian cancer with different responses to platinum-containing chemotherapy.
Authors: Sagakyants Aleksandr B. , Bondarenko Elena S. , Yakubova Darya Yu. , Ulianova Elena P. , Zhukova Galina V. , Menshenina Anna P. , Novikova Inna A. , Verenikina Ekaterina V. , Adamyan Meri L. , Cherkasova Anna A.
Published: June 2021

e17527

Background: Resistance to chemotherapy is a complex problem in the treatment of patients with ovarian cancer (OC), and this phenomenon is associated, among other things, with the presence of cancer stem cells (CSCs). The purpose of the study was to determine the amount of CSCs in tumors of OC patients with different responses to chemotherapy they receive. Methods: Samples of ovarian tumors were obtained from 100 patients (aged 29-79 years) with advanced ovarian cancer stage IIIC-IV with/without ascites. All patients recruited in 2016-2020 received standard combination treatment with surgery and platinum-containing polychemotherapy (Pt CT). Based on the results of neoadjuvant Pt CT, patients were divided into groups: patients with stabilization or progression–group 1 “without effect”; patients with complete/partial regression–group 2 with positive effect. All patients gave their informed consent for the study. Cell suspension obtained from the tumor fragments was processed using monoclonal antibodies labeled with various fluorochromes: CD45-APC-Cy7, CD44-FITС, CD133–РЕ according to the manufacturer's instructions (BD, USA). The percentage of CSCs was determined using the FACS Canto II flow cytometer (BD, USA). The amount of cells with CSC markers (CD44+, CD133+, CD44+CD133+) was calculated as a percentage from the total amount of CD45--cells. Statistics: STATISTICA 13 (StatSoftInc., USA). Results were presented as Me (LQ; UQ). The significance of differences was assessed using the Mann-Whitney test (the differences were considered significant at p<0.05). Results: The amount of CD45- _cells, as well as CD45-CD44+ cells, in OC tumors did not differ between patients of groups 1 and 2: 79.0 (72.1; 85.9) vs. 82.8 (76.7; 89.0), and 6.2 (3.3; 9.1) vs. 6.6 (3.5; 9.8), respectively. The percentage of cancer cells with the CD45-CD133+ phenotype in group 2 was significantly lower than in group 1: by 52% (p≤0.05), 3.2 (2.4; 3.9) vs. 6.7 (3.8; 9.6), respectively. The amount of CD45-CD44+CD133- CSCs in tumors in group 1 was lower than in group 2: by 82% (p≤0.05), 0.6 (0.3; 0.7) vs. 3.3 (1.8; 4.7), respectively. Conclusions: The results demonstrated certain differences in the distribution of CSCs in tumors of OC patients with different sensitivity to chemotherapy, which may be one of the factors determining the treatment outcomes.
Impact on survival of surgical therapeutic strategy in the initial management of advanced ovarian cancer: A study from the Cote d’Or gynaecological cancer registry from 1998 to 2015.
Authors: Amet Alix , Costaz Hélène , Fumet Jean-David , Arnould Laurent , Favier Laure , Beltjens Françoise , Bengrine Leila , Dabakuyo Tienhan Sandrine , Coutant Charles
Published: June 2021

e17537

Background: The management of ovarian cancer is based on a combination of surgery and chemotherapy. The aim of surgery is to achieve zero residual tumour at the end of the procedure. In advanced stage ovarian cancer, two therapeutic approaches are possible: primary debulking surgery, or primary chemotherapy followed by interval debulking surgery. The primary objective of this study was to describe overall survival (OS) in FIGO stage III and IV ovarian cancers according to the therapeutic sequence (i.e. primary surgery or interval surgery). Methods: We performed a retrospective, observational study using data from the gynecological cancer registry of the Cote d’Or, for patients diagnosed with FIGO stage III or IV ovarian cancer between 1998 and 2015. We recorded FIGO stage, histological type, treatment and completeness of cytoreduction. Results: In total, 460 patients were included. OS at 5 years was 47% in patients with primary surgery, versus 38% in patients with interval surgery (p = 0.06). Five-year OS was 45% in patients with complete cytoreduction, versus 30% in those with incomplete cytoreduction (p < 0.001). The rate of complete cytoreduction was 43% in patients with primary surgery, versus 55% in those with interval surgery. Conclusions: OS appears to be slightly better in patients receiving primary surgery, and when cytoreduction is complete. Every effort should be made during surgery to achieve complete cytoreduction, by an experienced team. Primary surgery should be preferred in these patients.
Characteristics of local inflammation in patients with uterine fibroids and endometrial cancer.
Authors: Zykova Tatiana A. , Zlatnik Elena Yu. , Nikitina Vera P. , Shevyakova Elena A. , Zhenilo Oksana E. , Verenikina Ekaterina V. , Ivanova Viktoria A. , Kruze Polina A. , Ardzha Anna Yu.
Published: June 2021

e17561

Background: Contribution of local inflammation to the course of endometrial cancer (EC) is of interest since it may aggravate the disease. Methods: The study included 25 women aged 62+1.6 years with histologically verified EC (group 1a), 29 women aged 48+8.4 years with uterine fibroids (UF) (group 1b) and 13 non-cancer women aged 42+2.3 years (group 2, controls). Vaginal swabs were taken prior to antitumor treatment. Relative expression of genes encoding the synthesis of IL1B, IL10, IL18, TNFA, TLR4, GATA3, and CD68 in comparison with the reference gene B2M was determined by Real-time PCR using the ImmunoQuantex kit (Russia). An integral parameter of an inflammation index was calculated using binary logistics, and the ratios of the listed indicators were also calculated. 12 parameters were analyzed in total. Groups Ia and Ib were compared with healthy people (p1) and with each other (p2). Results: 4 of 12 studied parameters in EC patients differed from control; no differences were found in UF patients. 7 statistically significant differences were registered between EC and UF. Relative expression of the gene encoding the synthesis of IL10 was maximal in EC (2.8+0.2 vs. 1.8+0.3 in healthy women (p1= 0.006) and 1.8+0.2 in UF (p2= 0.002)). The IL10/IL18 ratio in EC statistically significantly exceeded the ratios in UF patients and in healthy women (61.4+21.7 (p1= 0.003), 46.3+32.2 (p2< 0.001) and 53.7+47.1 respectively). The TNFA/IL18 ratio in EC patients was also higher than in UF patients (1.1+0.7 vs. 0.5+0.2 (p2= 0.035)) due to higher TNFA levels (3.7+0.1 vs. 3.3+0.1 (p2= 0.006)), one of which effects includes stimulation of neoangiogenesis. The ratio of TLR4/GATA3, on the contrary, was lower in EC than in UF (0.7+0.3 and 1.5+0.9 respectively (p2= 0.001). Apparently, it characterized antimicrobial immunity because both of these genes are involved in the response to PAMP (TLR4) and in the genesis of intraepithelial lymphocytes related to innate immunity, as well as in the development of a humoral response via stimulation of Th2 (GATA3). The latter, in addition, is involved in the ontogenesis some organs, including the vagina and uterus. The highest TLR4/GATA3 ratio was found in UF, which, in our opinion, indicated the predominance of the inflammatory process in UF and local immunosuppression in EC. The inflammation index determined with the ImmunoQuantex test system did not differ between the studied groups of women. Conclusions: Some differences were observed in local reactions of immunity and inflammation in benign and malignant uterine tumors, involving the prevalence of immunosuppressive and angiogenic factors in EC and inflammatory factors in UF.
Cost-effectiveness (CE) analysis of pembrolizumab as first-line (1L) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the United States (US).
Authors: Ramakrishnan Karthik , Jain Disha , Gandhi Jyotika , Chirovsky Diana Romana , Borse Rebekah
Published: June 2021

e18013

Background: Pembrolizumab received FDA approval in 1L R/M HNSCC as monotherapy (P) in patients with combined positive score (CPS) ≥1, and in combination with platinum + 5-Fluorouracil (5-FU) chemotherapy (P + C) in the total population, based on KEYNOTE 048 (KN048) trial. Taking a US payer perspective, we evaluated the CE of P and P + C versus KN048 trial comparator cetuximab + platinum + 5-FU (EXTREME regimen), and other comparators commonly used in the US (i.e. cisplatin+docetaxel+cetuximab [TPEx regimen], platinum + paclitaxel/taxane [Pt + T] and platinum+5-FU [Pt + F]). Methods: A 3-state partitioned-survival model was used to project costs and outcomes over 20 years with a 3% annual discount rate. For P, P + C and EXTREME, health state occupancy was based on KN048 trial results with long-term parametric extrapolation of progression-free survival (PFS) and overall survival (OS) guided by statistical criteria. A network meta-analysis (NMA) was applied to the P and P + C interventions in KN048 to project the PFS and OS outcomes for other comparators. The time on treatment (ToT) for P, P+C and EXTREME was derived from the KN048 trial, whereas for other comparators, ToT was approximated by PFS. Costs of 1L and subsequent treatments, disease management, adverse event, and terminal care were included. Utilities were derived using the EuroQoL five-dimension data from KN048 and a US value set. Results: CE ratios, total and incremental costs and quality-adjusted life years (QALYs) from the base case analysis are summarized in the table below. P was more effective and less costly (i.e. dominant) versus EXTREME and TPEx. P + C was highly cost-effective versus EXTREME ($1,789/QALY) and TPEx regimen (dominant). CE ratios for both P and P + C versus all comparators were below a $100,000/QALY willingness-to-pay threshold. Probabilistic sensitivity analysis also showed a 100% CE probability for P and P + C at the $100,000/QALY threshold. Conclusions: P and P + C are cost-effective treatment options in the US with CE ratios below $100,000/QALY gained versus commonly used therapies in 1L R/M HNSCC.[Table: see text]
Prognostic nomogram for pediatric nasopharyngeal carcinoma in the intensity-modulated radiotherapy era.
Authors: Zhang Yizhuo , Hong Ye , Chen Huimou , Wu Yanpeng , Zhu Jia , Huang Junting , Wang Juan , Sun Feifei , Que Yi , Zhang Lian , Chen Binbin , Lu Suying
Published: June 2021

e18036

Background: There was no prognostic nomogram model exclusive for pediatric nasopharyngeal carcinoma (NPC). This study aimed to establish a nomogram, incorporating clinical characteristics and MRI features, for predicting progression-free survival (PFS) and overall survival (OS) in pediatric NPC. Methods: Children with nonmetastatic NPC treated with intensity-modulated radiotherapy (IMRT) in Sun Yat-sen University cancer center in China between 2004 to 2018 were enrolled and separated in a 3:1 ratio into a training cohort and a validation cohort. The data of the training cohort were analyzed to identify the variables independently associated with PFS and OS, and these variables were used to construct the prognostic nomogram. The predictive accuracy and discriminative capability of the nomogram were evaluated by the calibration curve and the concordance index (C-index). The nomogram was validated in the validation cohort. Results: A total of 200 patients were enrolled: 152 in the training cohort and 48 in the validation cohort. Age, serum lactate dehydrogenase level, and invasion of the clivus were the independent prognostic factors for PFS in the training cohort. The C-index of the nomogram constructed using these variables was 0.86. The calibration curve showed consistency between the nomogram prediction and the actual observation for 5-, 6- and 7-year PFS. In the validation cohort, the C-index of the nomogram was 0.64, and the calibration curve showed good consistency between the nomogram and actual observation for 5-, 6- and 7-year PFS. For OS, no independent prognostic factors were identified. Conclusions: The prognostic nomogram could be a useful tool for predicting PFS in pediatric NPC patients treated with IMRT.
Neoadjuvant intraarterial cytoreductive chemotherapy for lacrimal gland adenoid cystic carcinoma: A 33-year single-institution experience.
Authors: Costa Philippos Apolinario , Pelaez Daniel , Tse David , Benedetto Pasquale W.
Published: June 2021

e18051

Background: Lacrimal gland adenoid cystic carcinoma (LGACC) has historically been associated with a poor prognosis even in localized disease, with the survival of 56% at 5 years and 49% at 10 years. In 1988, our group treated the first patient with neoadjuvant intra-arterial chemotherapy (IACC) followed by adjuvant chemoradiation. Since then, we use this protocol as the standard approach for localized LGACC. Herein, we aim to analyze the clinical characteristics and outcomes of LGACC patients at a single academic institution treated with the protocol to provide information on this approach's efficacy. Methods: We prospectively assessed all patients with pathologically confirmed LGACC treated at Bascom Palmer, Sylvester Comprehensive Cancer Center, or Jackson Memorial Hospital between 1988 and 2021. We calculated overall survival (OS) using the Kaplan-Meier and Cox proportional-hazards modeling methods with Log-Rank Test to estimate the 95% confidence interval. Results: 42 LGACC patients were identified, and 37 (88%) underwent IACC, with 2 (5%) being metastatic at the time of the protocol. In our cohort, the median follow-up was 10 years, 21 (56%) were men, and the median age at diagnosis was 42 (range 20-72). The average tumor size was 3cm (range 0.8-7.6). The dominant histological pattern was cribriform (n = 23, 54%), followed by basaloid (n = 6, 14%) and solid (n = 6, 14%). 16 patients underwent whole genome sequencing, and the most common mutations found were NOTCH1 (n = 7, 41%), ATM (n = 4, 25%), BPTF (n = 4, 25%), FGFR 2 (n = 3, 18%), Frem3 (n = 3, 18%), and NOTCH2 (n = 3, 18%), with additional biomarker data forthcoming. The 5, and 10-year survival rates were 85% (95% CI 73–97) and 71% (95% CI 53-89), respectively, giving and overall mean survival of 23 years (95% CI 19–28). The risk of death was higher with a tumor size larger than 3 cm and with bone invasion (HR: 6.5 and 7.5 respectively; P < 0.05). Conclusions: Despite the historically described poor prognosis, patients with LGACC treated with IACC have an excellent prognosis. Future research on tumor molecular characteristics might identify susceptibility to targeted therapies such as NOTCH or FGFR inhibitors that could be incorporated into the IACC protocol, further extending its benefits.
Racial/ethnic disparities in oropharyngeal cancer outcomes among males in the United States (2005-2016): A population-based retrospective cohort study.
Authors: Villalona Seiichi , Stroup Antoinette , Villalona Satsuki , Ferrante Jeanne
Published: June 2021

e18576

Background: The incidence of male oropharyngeal cancers (OPCa) has increased rapidly during the past two decades in the United States. Little is known regarding differences in OPCa incidence and outcomes by race/ethnicity and human papillomavirus (HPV) status. Methods: Population-based retrospective cohort study of 175,843 males diagnosed in U.S. with OPCa from 2005-2016 in the North American Association of Central Cancer Registries. Outcomes included: incidence trends of OPCa by race/ethnicity [Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Hispanic, Other] and histology-based HPV status; late-stage diagnosis; 5-year cumulative and mean survival; and mortality (cause-specific, all cause). Results: The majority of male OPCa were HPV-related (92.2%) and in NHW (83.6%), with marked increase in late-stage HPV-related OPCa among NHW. No difference in late-stage diagnosis was observed between NHW, NHB (aOR, 0.99, 95% CI, 0.94-1.04), and Hispanics (aOR, 0.98, 95% CI, 0.92-1.04), while other race had lower odds of late-stage diagnosis (aOR 0.87, 95% CI, 0.79-1.01). HPV-related cancers (aOR, 3.47, 95% CI, 3.33-3.62), Medicaid (aOR, 1.37, 95% CI, 1.28-1.46) and no insurance (aOR, 1.44, 95% CI, 1.32-1.56) were independent predictors of late-stage diagnosis. NHB (69.72 months, 95% CI, 68.14-71.31) and Hispanics (91.89 months, 95% CI, 89.87-93.91) had lower unadjusted mean survival in HPV-related OPCa relative to NHW (99.63 months, 95% CI, 99.18-100.07; p < 0.01). Higher cancer-specific mortality was observed among NHB (aHR, 1.79, 95% CI, 1.71-1.86), Hispanics (aHR, 1.07, 95% CI, 1.01-1.14), HPV-related OPCa (aHR, 1.17, 95% CI, 1.11-1.24), age > 54 years, insurances other than private, residence in counties with higher poverty, and geographic regions other than the Northeast. Adjusting for treatment attenuated associations but did not eliminate the observed cancer-specific mortality, except in Hispanics and residence in the South. Conclusions: There has been a sharp increase in HPV-related late-stage OPCa among NHW males over the past decade. Despite no racial/ethnic differences in late-stage diagnosis, NHB had highest mortality that was not explained by treatment. HPV vaccination and possibly, oral cancer screening should be promoted, especially in NHW males. Further research is needed to elucidate comorbidities and possible biologic mechanisms responsible for the higher OPCa mortality among NHB males.
Patient adherence to LungRADS recommendations at an academic institution.
Authors: Lin Yannan , Zhang Tianran , Hsu William , Aberle Denise R. , Prosper Ashley
Published: June 2021

e18592

Background: The National Lung Screening Trial (NLST) demonstrated a 20% reduction in lung cancer mortality when screened with low dose computed tomography (LDCT) as opposed to chest radiography. Notably, participants’ adherence to the screening protocol was 90%. To date, published evidence on the adherence of patients enrolled in clinical lung cancer screening (LCS) programs to LungRADS recommendations is limited. We investigate the adherence rate at our institution and determine the predictors of non-adherence to LungRADS recommendations. Methods: We performed a retrospective analysis on patients aged 50-80 years at time of baseline screen with initial screening exam at our institution between Jan 1, 2015 and Jan 12, 2021. Patients were excluded if 1) their follow-up period was insufficient to determine adherence as of Jan 28, 2021, 2) the follow-up recommendation was inconsistent with LungRADS guidelines, or 3) they died before the expected follow-up date. Adherence was defined as completion of recommended or more invasive follow-up at our institution within 12 months for LungRADS 0, 15 months for LungRADS 1/2, 9 months for LungRADS 3, 5 months for LungRADS 4A, and 3 months for LungRADS 4B/4X. A univariate logistic regression was used to determine predictors of non-adherence. Results: Among the 2120 eligible patients, 1266 (60%) were male and 854 (40%) were female with a median age of 65 at the baseline screen. One thousand four hundred and seventy-seven (70%) patients identified as White, 286 (13%) declared another racial group, and 357 (17%) did not disclose their race. One hundred and nine (5%) patients identified as Hispanic and 165 (8%) patients did not state their ethnicity. There were 1113 (53%) former smokers, 748 (35%) current smokers, and 259 (12%) patients of unspecified smoking status. Median tobacco exposure was 30 pack years (range 0.15 to 240). Fifty-seven percent of patients had private or commercial insurance while 39% had Medicare as primary insurance (3 patients were unspecified). The distribution of baseline LungRADS scores was 0: < 1%, 1: 14%, 2: 71%, 3: 7%, 4A: 4%, 4B: 2%, and 4X: < 1%. Overall adherence was 31% with 0: 38%, 1: 21%, 2: 27%, 3: 46%, 4A: 68%, 4B: 80%, and 4X: 100%. Of the 1463 non-adherent patients, 528 completed a follow-up exam beyond the expected date while 935 did not have any follow-up before the end of the study. Patients who were over 65 at baseline screen (OR = 1.34, 95% CI: 1.11, 1.61), former smokers (OR = 1.24, 95% CI: 1.02, 1.52), had Medicare insurance (OR = 1.35 95% CI: 1.12, 1.63), or had LungRADS 3/4 (referent: LR 1/2, OR = 4.29, 95% CI: 3.32, 5.55) were more likely to be adherent. Conclusions: Patient adherence to LungRADS recommendations at time of baseline screen in clinical practice is suboptimal, particularly among those with negative screens (LungRADS 1/2), with a non-adherence rate of > 70%. Baseline LungRADS scores, age, smoking status, and insurance are predictive of LCS non-adherence.
A Retrospective audit comparing the neutropenic complications in the Pre-COVID and COVID era from a tertiary care center.
Authors: Warrier Narayanankutty , Chandramohan Deepa , Vallathol Dilip Harindran , Parameswaran Prasanth V. , K. V. Sajeevan , P. S. Sreedharan
Published: June 2021

e18619

Background: The COVID era has shown a rise in Intensive Care Unit (ICU) admissions. This is mainly due to COVID related complications. On the contrary, the public around the world have become more aware about maintaining proper hygiene by wearing masks , using hand wash and keeping themselves clean. As an audit, we conducted a retrospective analysis comparing neutropenic complications during the pre COVID and COVID times at our tertiary care cancer hospital. Methods: We collected data of febrile neutropenia admissions in ICU from March to July 2019-Non Covid (NC) and March to July 2020-Covid (C). The data collection was done including data on nadir total WBC count, use of GCSF, positive cultures, type of malignancy and deaths. The statistical analysis was done using SPSS software version 22. Results: There were 15 patients in the NC dataset and 18 patients in the C dataset. The mean age of NC was 59 (SD-9.2) and that of C was 57. 3 (SD-14). The age and sex were comparable in both the groups. The number of solid organ malignancies constituted 5 (33.33%) in NC set and 8 (44.44%) in C set. The hematological malignancies constituted 10 in each of C and NC sets. Gram negative sepsis was seen in 26.67% and 22.22% in NC and C dataset respectively. There were 4 (26.67%) deaths in NC group and 5 (27.28%) C group. Growth factors were received by 9 (60%) patients in NC group and 15 (83.3%) patients in the C group (p=0.0005). There was no significant difference in the admission, complication and death rates in ICU when comparing the two groups. These results have been depicted in Table. Conclusions: Despite the precautions taken by community during the COVID times, we conclude that there was no significant difference in the neutropenic complications. It also suggests that most of the neutropenic infections are related to the person’s immunity rather than community transmission. The study limitation is that this is a single center study but further audits and prospective studies are warranted in this regard. Keywords - COVID, Non COVID, Neutropenia, Intensive Care Unit. [Table: see text]
30-day readmission after TAVR (Transcatheter Aortic Valve Replacement (TAVR) in patients with malignancy.
Authors: Upadhyay Banskota Shristi Upadhyay , Salazar Miguel , Gauto Estefania , Macchi Hugo , Shrestha Prajwal , Khanal Nabin
Published: June 2021

e18620

Background: Hospital readmissions after cardiac procedures are increasingly the major focus of quality improvement efforts. Although some reflect appropriate care, others are potentially preventable readmissions (PPRs). We aim to describe the burden, timing, and factors associated with readmissions after transcatheter aortic valve replacement (TAVR) in patients with malignancy. Methods: We performed a retrospective study of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an index admission for TAVR with a concomitant diagnosis of malignancy. We aimed to identify 30-day readmission rate, mortality, healthcare related utilization of resources and other independent predictors of readmission. Results: A total of 2,213 patients with malignancy underwent TAVR. The 30-days readmission rate was 16% (n=355). Main causes of readmissions were found to be heart failure, sepsis, acute hypercapnic respiratory failure, coronary artery disease with angina, and AKI with ATN. Readmitted patients were more likely to come from small metropolitan areas (43.1% vs 33.6, p≤0.01), micropolitan areas (1.4% vs 0.35%, p≤0.01), rural hospital (20.3% vs 8.8%, p≤0.01), non-teaching hospital (23.5% vs 9.1%, p≤0.01), and small sized hospitals (11.5% vs 4%, p≤0.01). Patients re-admitted were more likely to have malnutrition (8% vs 3.2%, p≤0.01), new VTEs (3.8% vs 0.6, p≤0.01), AKI (26% vs 13.6%, p≤0.01) and deaths (4.6% vs 1.7%, p≤0.01). The total health care in-hospital economic burden of readmission was $5.9 million in total charges and $25 million in total costs. Independent predictors of readmission were disposition to short-term skilled nursing facilities, home-health care, and sepsis. Conclusions: We concluded that readmissions after TAVR in patients with malignancy are associated with higher in-hospital mortality rate and pose a higher health care burden. We also identified risk factors that can be targeted to decrease readmissions after TAVR, health care burden, and patient mortality.[Table: see text]
Cardiotoxic safety communications after FDA approval of novel cancer therapies.
Authors: Bonsu Janice , Kola-Kehinde Onaopepo , Kim Lisa , Ruz Patrick , Lustberg Maryam B. , Brammer Jonathan Edward , Addison Daniel
Published: June 2021

e18629

Background: Proliferation of novel anticancer therapies has dramatically improved survival. However, in practice, cardiovascular disease (CVD) events have become an increasing concern. Post-market safety communications by the US Food and Drug Administration (FDA) are a primary source of new safety information for patients and providers. Yet, the prevalence and factors associated with the issuance of CVD warnings among cancer therapies are unknown. Methods: Leveraging the Drugs@FDA database and publicly available FDA drug reviews, we identified all anticancer drugs given new-drug applications from 1998-2018. Characteristics related to approval, including drug class, therapeutic area, priority review status, accelerated approval status, orphan product status, regulatory review times, near-regulatory deadline approval status, and post-market safety events were evaluated. Post-market safety communications were defined as the composite of safety-related drug withdrawals and the issuance of black box label warnings or precautions. CVD was defined as heart failure, hypertension (HTN), coronary disease, myocardial infarction, stroke, thromboembolic disease, arrhythmia/electrocardiographic change, or sudden cardiac death. Multivariable logistic regression was used to assess for characteristics associated with the need for CVD safety communications. Results: Overall, there were 125 novel anticancer therapies, including 24 biologics, 10 immunotherapies, and 48 targeted drugs. There were 177 safety communications (41 black box warnings, 7 withdrawals, 4 dose adjustments, and 84 general warnings). Cardiac safety warnings were issued for 63 (51.2%) of therapies, including 23 (36.5% of all) black box warnings. CVD was the most common reason for a black box warning; Table. Among all CVD warnings, arrhythmias (21.6%) followed by heart failure (13.9%), thromboembolic disease (13.9%), uncontrolled HTN (11.8%), sudden CVD death (9.0%), ischemic disease (6.9%), stroke (4.9%), and other CVD events (12.5%) were found. In a multivariable model, only therapeutic class and prior in-class cardiotoxicity were associated with the issuance of CVD safety communications. Conclusions: Among novel cancer therapies, cardiac safety communications are prevalent.[Table: see text]
Pathway use and concordance in affiliated academic and community oncology practices.
Authors: Edge Stephen B. , Liu Lu , Stefaniak Nessa , Soucise Allison , Soniwala Saifuddin , George Saby , Kuvshinoff Boris W. , Tear David , Murphy Monica L. , McKinney Mishellene
Published: June 2021

e18639

Background: Clinical oncology pathways (COP) provide treatment (Rx) decision support and allow detailed quality oversight. There are limited data on use of COP and the proportion of patients receiving COP recommended Rx (concordant / “On Pathway” Rx – OnP) and on the reasons for COP non-concordant “Off Pathway” Rx (OffP). Methods: COP concordance and reasons for OffP Rx were evaluated and compared at an NCI-designated cancer center (Roswell Park Comprehensive Cancer Center – RP) and its 5 affiliated community practice sites (Roswell Park Care Network – RPCN) for COP Rx decisions from 10/1/19 – 9/30/20. Elsevier ClinicalPath Oncology COPs (formerly Via Oncology) were implemented in 2018 at RP and RPCN and are completed at initiation of any systemic Rx. COPs cover about 85% of cancers, excluding most hematologic cancers. COP Rx decisions are classified as OnP (including Rx on a clinical trial) or OffP. All OffP decisions are reviewed retrospectively to identify the reasons for OffP Rx. Differences in OnP rates at RP and RPCN were compared by chi square test or Fisher’s test overall and for 7 cancer type groups and for adjuvant Rx (ADJ) and metastatic disease (MET). ADJ/MET comparison excluded gynecologic cancer (GYN), myeloma and myelodysplastic syndrome (MDS) because COPs do not classify ADJ vs MET for these. Results: At RP there were 4,291 Rx decisions for 3,361 patients and at RPCN 1,349 Rx decisions for 1,198 patients. Breast cancer was the most common cancer type (18% of patients at RP and 36% at RPCN). Proportions of patients with GYN, melanoma, sarcoma, and GU cancers were higher at RP and similar for GI, thoracic and myeloma/MDS. Among 3,153 ADJ and MET Rx decisions at RP, 55% were for METS vs. 36% of 1,096 decisions in the RPCN. Pathway decision concordance (OnP) rates overall were 85% at RP and 89% at RPCN (p < 0.01- Table). OnP rates for ADJ Rx were 89% at RP and 92% at RPCN (p = 0.05), and for MET 84% at RP and 86% at RPCN (p = 0.53). Most OffP Rx was for medically valid reasons including comorbidity, new/targeted therapies, and prior Rx precluding COP recommended Rx. Conclusions: COP concordance was slightly higher in community practice, potentially because newer therapies, patients with greater morbidities and more complex cancers are in the academic practice. RP had a higher proportion of MET cases consistent with the tertiary practice treating more advanced cancer. OffP Rx was higher with MET, likely related to the nuances of Rx of MET cancer and new therapies not yet in pathways. OffP Rx was fully justified in most cases.[Table: see text]
Mental health care utilization among veterans with castration-resistant prostate cancer receiving abiraterone or enzalutamide.
Authors: Tsao Phoebe A. , Burns Jennifer A. , Entenman Shami , Kumbier Kyle , Sparks Jordan , Bohnert Amy S. B. , Skolarus Ted A. , Caram Megan Veresh
Published: June 2021

e18680

Background: Abiraterone and enzalutamide are oral therapies widely used to treat men with castration-resistant prostate cancer (CRPC). Recent data have suggested potentially worsened quality of life and depression with use of enzalutamide compared to abiraterone. Because Veterans are at a higher risk for mental health conditions, we sought to compare mental health service utilization in Veterans with CRPC receiving enzalutamide to those receiving abiraterone. Methods: The Veterans Health Administration Corporate Data Warehouse was used to identify men with CRPC who received abiraterone or enzalutamide for ≥ 30 days as first-line treatment between 2010-2017. We compared the rate of mental health visits per 100 patient-months for men on abiraterone versus enzalutamide using an exact rate ratio test, assuming Poisson counts. Results: Among 2902 male Veterans, 68.6% (n=1992) received abiraterone and 31.4% (n=910) enzalutamide as first-line therapy. Men who received enzalutamide were older (76 vs 74, p<0.01) and had a higher comorbidity burden (Charlson Comorbidity Index [CCI] ≥ 2 in 28.7% vs 21.6%, p<0.01); no differences were noted in race or prevalence of preexisting documented mental health diagnoses. Median time on drug was 8 months for both medications. There was no difference in the rate of mental health visits per 100 patients-months on enzalutamide versus abiraterone (6.6 v. 6.7, p=0.66). However, within patient sub-groups, men who were age 75 or older, not married, or without notable comorbidities had lower rates of mental health visits with enzalutamide compared to abiraterone; whereas those who were younger than 75, married, had higher comorbidities, or a preexisting mental health diagnosis had higher rates of mental health visits with enzalutamide (Table). Conclusions: Among Veterans with CRPC who received a novel antiandrogen therapy first-line, there was no difference in engagement in mental health care between those who received abiraterone versus enzalutamide. Sub-group analysis revealed significant differences between patients on the two medications in demographic and diagnostic characteristics associated with number of visits, suggesting that vulnerability for mental health symptoms may vary by medication type. Further work in understanding the long-term impact of novel antiandrogens on mental health is needed.[Table: see text]
Real-world overall response rate and other outcomes related to originator and biosimilar rituximabin patients with chronic lymphocytic leukemia or non-Hodgkin’s lymphoma in the United Kingdom.
Authors: McBride Ali , Daniel Shoshana , Driessen Maurice T. , Szende Agota , Choudhry Azhar , Tian Marc , Ariely Rinat , Thompson Stephen
Published: June 2021

e18696

Background: Rituximab is a chimeric anti-CD20 monoclonal antibody therapy, used primarily for treating chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). Rituximab-abbs, the first rituximab biosimilar, was approved in the UK in 2017 and was expected to significantly reduce drug acquisition costs, but there is a lack of real-world evidence regarding patient outcomes with rituximab-abbs. This non-interventional study assessed the real-world effectiveness and tolerability of rituximab-abbs and rituximab in treatment-naive patients with CLL or NHL. Methods: Anonymized data on patient characteristics, response to treatment, healthcare resource utilization and costs were abstracted retrospectively via an online physician survey. UK-registered hematologists and oncologists reported on randomly selected patients aged ³18 years from four cohorts with documented CLL or NHL, who had received rituximab-abbs or rituximab as first-line immunotherapy (between January 1, 2018 and June 30, 2019). Patient outcomes data were provided from first treatment to the last date of follow-up available in the medical records. Results: In total, 46 physicians abstracted data from 201 patient charts. Demographic profiles of the cohorts were similar. For both treatments, the overall response rate (ORR) was very high for patients with CLL or NHL (Table) along with rates for six-month progression-free survival (96–98% across cohorts) and one-year survival (98–100% across cohorts). Most patients did not experience a grade ≥3 adverse event during treatment (54–66% across cohorts); the most common grade ≥3 adverse events were neutropenia, fatigue, anemia and infusion reactions. Healthcare resource utilization was similarly high across cohorts, driven by drug costs, diagnostic testing, oncologist office visits, and day case hospital admissions. Mean annual savings of approximately £1,000 per patient were seen with rituximab-abbs, attributable to first-line treatment costs. Conclusions: The originator (rituximab) and biosimilar (rituximab-abbs) products yielded comparable efficacy and tolerability in treating CLL and NHL in routine UK clinical practice, with rituximab-abbs demonstrating cost-savings. These findings should inform decision-makers on the potential for cost reductions where the biosimilar rituximab-abbs is available as a treatment alternative.[Table: see text]
Evaluation of cardiotoxicity related to cancer treatment in an urban safety-net hospital.
Authors: Lee Michelle Jeung-Eun , Chang Eric , Onwuanyi Anekwe , Jain Sanjay R.
Published: June 2021

e18804

Background: Improvements in survival of cancer patients has led to an increased awareness of the long-term cardiac effects of chemotherapy. American Society of Clinical Oncology (ASCO) Clinical Practice Guideline emphasizes the needs of identifying patients with higher risk for cardiovascular toxicity prior to treatment initiation. African American (AA) race has been associated with higher incidence of cardiotoxicity and resultant incomplete adjuvant therapy compared to white patients. Here, we investigate the utilization of various imaging modalities to monitor chemotherapy-induced cardiotoxicity in a predominantly AA breast cancer population at the safety-net hospital. Methods: This study was a retrospective analysis of breast cancer patients (n = 33) who received trastuzumab, doxorubicin, and/or paclitaxel between year 2018 and 2020 at the safety-net hospital in Atlanta, Georgia. Patient demographics, clinical characteristics, pathologic variables as well as utilization of echocardiography, echocardiography with global longitudinal strain (GLS), and multigated acquisition scans (MUGA). Results: The majority of patients were AA female (27/33, 81.8%) and the mean age at diagnosis was 52 ± 13.2 years. 11/33 (33%), 24/33 (72.7%), and 20/33 (33.3%) were treated with trastuzumab, paclitaxel, and doxorubicin respectively. Baseline left ventricular ejection fraction (LVEF) was assessed in 32/33 (96.7%) of patients: MUGA 21/32 (65.6%), echocardiography 10/33 (31.3%), and echocardiography with GLS 1/32 (3.1%). 13/32 (40.6%) patients underwent repeated imaging, with the average time between repeat MUGA and echocardiography being 254.3 and 147 days respectively. LVEF decrease of > 10% was noted in 4 patients with repeat MUGA but in none of the repeat echocardiography group. Only 5 patients had echocardiography with GLS over the study period, of which 2/5 (40%) had a drop in GLS in the setting of normal ejection fraction, consistent with occult LV systolic dysfunction. Conclusions: Our study suggests that African American patients at a safety net hospital receive the equivalent level of cardiac surveillance during cancer treatment. However, GLS imaging is underutilized in the detection of subclinical cardiac dysfunction in breast cancer patients receiving chemotherapy. Larger, long terms prospective studies are needed to assess the implications of abnormal GLS and progression to clinical left ventricular systolic dysfunction in the AA breast cancer population.
Impact of COVID-19 in the screening and treatment of breast cancer in the Brazilian public health system: Data from a healthcare data warehouse.
Authors: Morelle Alessandra Menezes , Venero Fernando Castilho , Dal Ponte Ferreira Rafael , Santanna Pedro Tofani , da Silva Rommel Fabricio Pereira , Zieguelmann Patrícia
Published: June 2021

e18807

Background:Since December 2019, the world is facing a pandemic caused by a novel coronavirus (SARS-CoV-2). We sought to analyze the behavior of cancer treatments and procedures in breast cancer in Brazil after the beginning of the COVID-19 pandemic through an artificial intelligence platform with real life data. Methods:Data evaluation was performed using the TechTrials platform. This platform created a unique healthcare data warehouse containing hundreds of different publicly available data sources about Brazilian Public Health System and with proprietary technology, developed several analytics products that explore and release real-world data (RWD) insights. For this analysis data were extracted from DATASUS – SIA (outpatients information system). For each outcome, data from January 2011 to February 2020 were used to adjust a time series to predict values for March to November 2020. Those values were compared with the observed ones. Results: Biopsies, mammograms and procedures showed a sharp decrease (41.9%, 73.7% and 31.1%, respectively), in April 2020 (following month of the first COVID-19 case in Brazil) with some recovering in the following months. All observed values of biopsies, the number of mammograms from March to October and the number of procedures in April and May were significantly smaller than the predicted ones. Number of women undergoing chemotherapy began to decline in August and remained falling until the last month of available data.(Table). Conclusions: This study is the first one that analyzes RWD of breast cancer screening, diagnosis and treatment in Brazil as a result of the COVID-19 pandemic. The impact of the decrease observed in screening and diagnosis is already evident in the number of women undergoing chemotherapy. These data will continue to be monitored in the coming months when only then will data be available for staging at diagnosis.[Table: see text]
U.S. budget impact analysis of an intravenousrituximab biosimilar versus subcutaneous rituximab for the treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL).
Authors: James Elizabeth , Trautman Holly , McBride Ali , Choudhry Azhar , Thompson Stephen
Published: June 2021

e18821

Background: Rituximab-abbs is a CD20-directed monoclonal antibody and the first rituximab biosimilar approved in the US, expected to significantly reduce drug acquisition costs. This budget impact model (BIM) estimated budgetary impact of replacing a proportion of rituximab/hyaluronidase human subcutaneous injection (SC-R) utilization for NHL (diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL]) and CLL with rituximab-abbs (IV-R-BIOSIM). The objective was to project incremental cost differences between IV-R-BIOSIM and SC-R over one year for a hypothetical 5-million-member US healthcare insured (Medicare) population. Methods: An illustrative BIM was developed to estimate 1-year drug and administration costs for a one-quarter shift in SC-R market utilization to IV-R-BIOSIM, with equal efficacy and safety assumed. Values for epidemiology, market share, drug dosing, administration, and costs were derived from scientific literature, product labels, and publicly available cost resources. Infused rituximab (IV-R) dosing assumed a mean body surface area (BSA) of 1.8m2. Annual dose counts of IV-R-BIOSIM or SC-R per patient were: 10 untreated FL with maintenance; 8 untreated FL (without maintenance), relapsed/refractory FL, or untreated DLBCL; 6 CLL. IV-R infusion duration was 3 hours. Drug acquisition and infusion/subcutaneous administration costs were from 2020 Average Sales Price pricing file and Centers for Medicare and Medicaid Services Physician Fee Schedule. SC-R costs included an initial IV-R originator dose. Patient cost share was based on 2020 Medicare Part B 20% cost-share for office visits and drugs. Univariate sensitivity analyses were conducted. A scenario analysis used 2-year dosing to estimate costs for further FL maintenance treatment. Results: For a 5-million-member insured population, an estimated 972 patients would receive rituximab for NHL or CLL; 49 would receive SC-R. Estimated total incremental savings for one year for a 13-patient shift from SC-R to IV-R-BIOSIM were $57,864, equating to $0.02 per enrolled member per year (PMPY). Per-patient incremental annual savings with IV-R-BIOSIM for one year ranged between $2,359–$8,186 (Table). The model was most sensitive to low or high BSA dosing and proportion of patients with CLL. Conclusions: This BIM estimated annual savings of over $57,000 ($0.02 PMPY) for a 5-million-member US payer following a 25% shift of current SC-R use to IV-R-BIOSIM. These findings demonstrate the potential economic benefits of IV-R-BIOSIM vs SC-R that may result in expanded access to rituximab therapy.[Table: see text]
Health care cost impact associated with adverse events (AEs) among treatments in third-line+ (3L+) relapsed/refractory follicular lymphoma (R/R FL).
Authors: Gaballa Sameh , Levy Moshe Y. , Keith Michael , Wong Alex , Proudman David , Nellesen Dave , Mamlouk Khalid
Published: June 2021

e18836

Background: Tazemetostat, a first-in-class oral, selective methyltransferase inhibitor of enhancer of zeste homolog 2 (EZH2) activity, was approved by the US Food and Drug Administration for treatment of patients with R/R FL after demonstrating single-agent antitumor activity in patients with wild-type or mutant EZH2. Phosphoinositide 3-kinase inhibitors (PI3Kis; idelalisib, duvelisib, and copanlisib) are also indicated for 3L+ R/R FL, but these drugs are associated with serious toxicities, such as neutropenia, infection, and immune-mediated toxicities. A matching-adjusted indirect comparison (MAIC) of tazemetostat with these 3 PI3Kis was previously presented in 3L+ R/R FL, showing that tazemetostat is associated with more favorable safety, and similar efficacy compared to each of the PI3Kis. The objective of this study was to estimate the difference in AE-related health care costs for each treatment. Methods: AE-related costs were sourced from a study of costs in patients hospitalized with AEs, using oncology-specific data when available. Matching-adjusted AE incidence was multiplied by costs related to each AE. Grade ≥3 AEs with incidence ≥5% for any of the evaluated treatments were included. Cost differences were estimated per treatment episode, based on duration of exposure in the tazemetostat clinical trial (9.3 months for tazemetostat, <7 months for the 3 comparators). Incidence rates were then converted to a monthly basis using an exponential curve. Results: The PI3Kis are estimated to incur $13,534 to $18,737 higher AE-related management costs per episode compared with tazemetostat. Adjusting for duration of exposure, each of the PI3Kis is project to cost $2,563 to $3,820 more per month than tazemetostat in AE-related costs. These estimates indicate that the AE-related cost impact of PI3Kis compared with tazemetostat is 3.4- to 6.1-fold higher on a per-episode basis, and 5.0- to 10.4-fold higher on a monthly basis. Conclusions: Quantifying the AE cost impact of tazemetostat based on AE incidence rates estimated by MAIC analysis adjusts for population differences and allows for more direct cost savings comparisons when accounting for duration of exposure to different treatments. Patients with 3L+ R/R FL who are treated with tazemetostat are estimated to incur substantially lower AE-related costs compared with PI3Kis (idelalisib, duvelisib, and copanlisib). [Table: see text]