bluuebunny/crossref_metadata_2025 huggingface dataset:
Schlafen 11 (SLFN11), a putative predictive biomarker of platinum/PARPi response, is frequently detected on circulating tumor cells (CTCs) in advanced prostate cancer.
Authors: Scher Howard I. , Fernandez Luisa , Cunningham Kate , Elphick Natalie , Barnett Ethan , Lee Jerry , Gilbertson Cole , Carbone Emily , Bourdon David , Blankfard Martin , Wang Eva , Jones Joshua Timothy , Tubbs Alisa , Anderson Amanda , Schonhoft Joseph D. , Wenstrup Rick
Published: June 2021

e17039

Background: Schlafen 11 (SLFN11) is a DNA repair protein (DNA/RNA helicase homology) that is recruited to stressed replication forks and leads to cell death. Recent ph II trial data in Extensive Stage Small-Cell Lung Cancer (ES-SCLC) [Byers et al. JCO 2018 PMID: 29906251] and a retrospective analysis of Circulating Tumor Cells (CTCs) and tumor tissue in patients (Pts) with advanced prostate cancer [Conteduca et al. Mol Cancer Therapeutics 2020 PMID: 32127465] suggested that SLFN11 expression predicts sensitivity to DNA damage targeting agents. In both contexts, metastatic tumor biopsies may not provide adequate material for profiling. We assessed the frequency of SLFN11 expression in CTCs isolated from blood in men with progressing metastatic Castration Resistant Prostate Cancer (mCRPC) and related expression to Homologous Recombination Repair (HRR) alterations identified in metastatic tumor biopsies profiled by MSK-IMPACT. Methods: 95 patients with progressing mCRPC about to start a new systemic therapy who had undergone pre-treatment metastatic tumor profiling by MSK-IMPACT and a matched blood draw for CTC profiling were selected. Blood was sent overnight to Epic Sciences and processed onto glass pathology slides and bio-banked until analysis. Detected CTCs (cytokeratin (CK) positive and leukocyte (CD45) negative) were analyzed for SLFN11 protein expression by immunofluorescence and correlated to Homologous Recombination Repair (HRR) alterations in metastatic biopsy from the bone, lymph node, or visceral metastases (15 PROFOUND genes). A mean of 1.2 mL of blood was analyzed per patient. Results: CTCs with SLFN11 expression (DAPI+, CK+, CD45-, SLFN11+) were detected in 28.4% (27/95) of the patient sample analyzed. SLFN11 signal was found to overlap with the nuclear DAPI signal. Individual CTC expression of SLFN11 in a sample was heterogeneous and ranged from a minimum of 2.9% to 100%. Seven of 10 (70%) of patients with a BRCA1/2 or ATM alteration had a least one SLFN11 expressing CTC. In contrast, in patients with other HRR alterations, only 20% (1/5) had CTCs with SLFN11. Sequencing of single CTCs is ongoing. Conclusions: SLFN11 expression is detected with high frequency in CTCs in men with progressing mCRPC. In whom CTCs are detected, the majority of patients with BRCA1/2 or ATM altered tumors also had SLFN11 expressing CTCs. The results support the prospective evaluation of CTC SLFN11 expression as a predictive biomarker for PARPi or platinum agents.
Survival outcomes of primary mediastinal germ cell malignancies based on clinicopathological characteristics: A SEER database analysis.
Authors: Shrivastava Trilok , Baral Binav , Pudasaini Garima , Lingamaneni Prasanth , Batra Kunnal , Upadhyay Banskota Shristi Upadhyay , Shrestha Rohit
Published: June 2021

e17055

Background: Primary mediastinal germ cell malignancies (PMGCM) account for up to 5% of all germ cell tumors. Different clinical and epidemiological factors have been known to have important prognostic implications as they contribute to a wide range of long term survival in individuals with PMGCM. Methods: We obtained data from the Surveillance, Epidemiology and End Results (SEER) database from years 1975-2016 to include cases with confirmed primary mediastinal germ cell tumors. After complete gathering of selected data, a total of 1,328 number of cohorts were obtained which were stratified by age, sex, race, type of malignancy, size of primary tumor, site, grade etc. and were analyzed by Cox regression using proportional hazard model. Kaplan Meier curves were also obtained to visualize all cause survival and stratified survival according to the types of malignancy. Results: In our study, we found the incidence of PMGCM to be 0.18 per 1,000 people with malignant cancer with a median age at diagnosis of 28 years, the age range being 21-50 years. 92.9% patients were males and 7.1% were females with more common occurrence in White patients (54.5%). Most common type of PMGCM was found to be Seminoma (23.4%) and 56.32% were poorly differentiated (Grade III), excluding unknown cases. About half (52%) of all was found to arise from the anterior mediastinum. 36% of all cases died from primary cancer. 42.7% underwent surgery, however there was no data for chemotherapy or radiotherapy. Mean survival time among all PMGCM was 37.5 months (p <0.05). A significant negative correlation was observed between survival time & age at diagnosis with Rp of 0.12 (p < 0.001). On survival analysis, age was a significant factor for decreased survival time with patients more than 50 years having a HR of 2 (p<0.001). Similarly, choriocarcinoma was associated with decreased survival time with HR 1.71 (p=0.03). Germinoma and seminoma were found to have higher survival time (HR 0.65 & 0.18; p=0.03 and <0.001 respectively). Patients with grade IV PMGCM had significantly lower survival time (HR 1.74, p<0.001). Patients who had undergone surgery had a better survival time compared to those who didn’t get surgery. There was no significant association of sex, race, tumor size or site with the survival time. Conclusions: Our study concludes that among PMGCM, seminomatous tumors have a favorable prognosis compared to non-seminomatous tumors with higher survival time. Age was found to be a significant contributing factor with ages over 50 having lower survival time. Surgical intervention was found to be associated with increased survival time, although it is important to recognize the lack of chemo-radiotherapeutics data.
Utilization and outcome of systemic chemotherapy for high-risk early-stage cervical cancer.
Authors: Takekuma Munetaka , Matsuzaki Shinya , Matsuo Koji
Published: June 2021

e17521

Background: To examine trends and outcomes of systemic chemotherapy for high-risk early-stage cervical cancer. Methods: This retrospective observational study queried the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from 2000-2016. Surgically-treated women with stage T1-2 cervical cancer who had high-risk factors (lymph node metastasis and/or parametrial invasion) and received adjuvant therapy were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for chemotherapy use versus external beam with chemotherapy (CCRT). Results: Among 2, 462 women with high-risk factor, 185 (7.5%) received systemic chemotherapy. Utilization of chemotherapy has significantly increased over time in multivariable analysis (adjusted-odds ratio per 1-year increment, 1.06, 95% confidence interval [CI] 1.02-1.09). In weighted models, adjuvant chemotherapy and CCRT had comparable survival among women aged < 40 (hazard ratio [HR] for all-cause mortality 0.73, 95%CI 0.41-1.33), adenocarcinoma or adenosquamous histologies (HR 0.90, 95%CI 0.62-1.32), and high-risk group based on nodal metastasis alone (HR 1.17, 95%CI 0.84-1.62). In contrast, chemotherapy was associated with increased all-cause mortality compared to CCRT among women aged ≥40 (HR 1.57, 95%CI 1.19-2.06), squamous histology (HR 1.63, 95%CI 1.19-2.22), and high-risk group per parametrial invasion alone (HR 1.87, 95%CI 1.09-3.20) or parametrial invasion with nodal metastasis (HR 1.64, 95%CI 1.06-2.52). Conclusions: Utilization of systemic chemotherapy for high-risk early-stage cervical cancer is increasing in the United States. Survival effects of adjuvant chemotherapy varied per patient and tumor factors, and this indication may be limited to those who are < 40 years with non-squamous histology and absence of parametrial invasion.
IL-17A and CCL2 in blood serum and circulating neutrophils in patients with ovarian tumors.
Authors: Gening Snezhanna , Abakumova Tatyana , Gening Tatyana
Published: June 2021

e17536

Background: During the ovarian carcinogenesis, circulating neutrophils (Nph) phenotype switches to the pro-tumor, with an increase in the Nph C-C motif ligand 2 (CCL2) expression. Proinflammatory interleukin-17A (IL-17A) is able to induce the CCL2 expression in Nph. The study aimed to evaluate the IL-17A and CCL2 levels in serum and circulating Nph in patients with ovarian tumors. Methods: The study included 97 ovarian cancer (OC) patients, 30 patients with benign ovarian tumors (BT) and the control (n=22). The levels of IL-17A (LLC "Cytokine", Russia) and CCL2 (Vector-Best-Volga, Russia) in serum and Nph lysate were assessed by ELISA. The systemic inflammation was assessed by neutrophil to lymphocyte ratio (NLR). Informed voluntary consent was obtained from all women. Statistical processing was performed using one-way ANOVA, Spearman correlations (Statistica 13.0 (TIBCO, USA)). Results: We found an increase in NLR in BT (4.3 ± 1.0) compared with the control (2.2 ± 0.1) (p = 0.020), a decrease in stage I-II OC (2.4 ± 0.2) compared with BT (p = 0.053), and an increase in stage III (4.5 ± 0.9) and IV (4.6 ± 0.5) compared with stage I-II OC (p = 0.054 and p = 0.046, respectively). The cytokines levels are presented in Table. The serum level of IL-17A in BT was higher than in the control (p = 0.010). In stage I-II OC, the serum IL-17A level was decreased in comparison with the BT (p = 0.004). In stage IV OC, the serum IL-17A was higher than in stage I-II (p = 0.015) and the control (p = 0.017). The level of IL-17A in Nph in BT did not differ from the control. In all stages of the OC, the IL-17A Nph level was lower than in the control (p1, 2, 3 = 0.0001). In stage IV OC, the expression of IL-17A in Nph was lower compared with stage III (p = 0.031). The serum and Nph levels of IL-17A were correlated only in stage I-II OC (r = 0.679, p = 0.011). The CCL2 serum levels in BT (p = 0.0002) and OC stage I-II, III, IV were higher compared with the control (p1 = 0.031, p2 = 0.001, p3 = 0.0005, respectively). The Nph CCL2 level was higher in BT than in the control (p = 0.001). In stage I-II OC, the expression of CCL2 in Nph was higher than in the control (p = 0.034), but lower than in the BT (p = 0.003). In OC stages III and IV, the Nph CCL2 level was higher than in the control, but did not differ from that in BT and stages I-II. In stage III OC, the CCL2 level in Nph negatively correlated with the serum IL-17A level (r = -0.405, p = 0.049). Conclusions: The pro-tumor polarization of circulating Nph is not IL-17A-dependent in patients with ovarian tumors. The patterns of the systemic immune response differ in benign ovarian tumors, early, and advanced ovarian cancer.[Table: see text]
Impact of universal health care on trends of incidence and mortality of cancers with screening recommendations in North America. A GLOBOCAN 2020 study.
Authors: Addula Mounika
Published: June 2021

e18513

Background: Cancers with screening recommendations in general population include breast, colorectal, cervical and prostate cancers. Our study is aimed at comparing the current and future trends in incidence and mortality amongst two biggest countries in North America (United States of America and Canada) with and without universal health care. Methods: Incidence and mortality data, their trends were obtained from the GLOBOCAN 2020 database. Crude rate and age standardized rate (ASR) data on incidence and mortality was obtained to minimize population-based distribution errors. Age groups were divided as 20-40, 40-49, 50-65 and above 65. Current incidence, mortality and future trends were obtained for both USA and Canada and compared. Results: Breast cancer incidence is higher in USA in all age groups. Mortality in the age groups of 20-39 and 50-64 is comparable in Canada and USA with ASR of 9.6 (Canada), 9.5 (USA) 197.2 (Canada), 195 (USA) respectively. Future trends predict higher increase in incidence and mortality in Canada in age groups of 40-49 (I: Canada +22.5% USA +19.2%. M: Canada +22.8% USA +19.3%) above 65 (I: Canada +52.3% USA +40.8%. M: Canada +70.9%. USA +57.3%). In age group above 65 the mortality is significantly higher in USA compared to Canada (p=0.001). The incidence of colorectal cancer is higher in USA compared to Canada. The ASR mortality of above 65 age group is significantly higher in Canada (p=0.0009) (M: Canada: 835.6 USA: 713.9). Mortality trends for the 2040 year are higher in the age groups of 50-64 and above 65 in Canada (50-64 M: Canada: +25.9% USA: +21.2%) (above 65: M: Canada +70.9% USA: +57.3%). Prostate cancer has higher incidence in 50-64 age group. The mortality is higher in 40-49 age group. The predicted incidence for 2040 is also higher in Canada in above 65 age group (Canada +48.3%, USA: 39.9%). Similarly, mortality is higher in Canada for the above 65 age group (Canada: +112.7%, USA: +90.2%). Both USA and Canada have higher mortality for prostate cancer in age group 40-49 than 50-64. Cervical cancer incidence and mortality ASR are higher in USA for age groups of 20-39 and 40-49. For ages 50-64, while the incidence is higher in the USA, mortality is higher in Canada. For ages above 65 the mortality is significantly higher in Canada (p=0.0022) compared to USA. The predicted percentage change in 2040, incidence and mortality of age group 40-49 is higher compared to 50-64. Conclusions: Though both health care systems have screening recommendations for breast, CRC, prostate and cervical cancers, mortality appears to be higher compared to the world population suggesting need for improvement in screening access/awareness. Younger adults (20-39) and middle age adults (40-49) appear to be more vulnerable population and need for improvement in identifying high risk population.
Do you hear us? Elevating the voice of patients from Asia Pacific (AP) and Middle East (ME) in pharmaceutical research.
Authors: Rihani Julie , Abdelbaky Noha Mohamed Mahmoud , Gulabani Chandra Rekha , Patel Dexter , El Sayegh Rami , Park JungHo , Dinboeck Michaela , Aubel Dawn , Slader Cassandra Alice
Published: June 2021

e18519

Background: Incorporating patient (pt) perspectives in the development of new therapies (from trial design to regulatory & reimbursement decisions) and providing pts with plain language summaries (PLS) of clinical trial results is increasingly important to minimise knowledge and experience disparities. One model to facilitate this in pharmaceutical research is via Patient Expert Panels (PEPs). Aim: To assess the feasibility & impact of PEPs consisting of members from AP&ME on the development of 1. PLS of data presented at ESMO and ASH 2020 for selected Novartis-sponsored clinical trials 2. Disease education material for sickle cell disease (SCD). Methods: Thematic analysis of meeting minutes from PEPs conducted between Sep – Dec 2020 was performed. Data relating to meeting duration were extracted. The responses from an 8-item survey of PEP members were analysed descriptively for 6 items, thematically for 2. Results: Five virtual PEPs were conducted, with a median duration of 60 mins [range 60-120]. In total, 9 PLS were reviewed (8 breast cancer, 1 CML) & 1 SCD education booklet. Five common themes emerged regarding the input & impact of the PEP [Table]. 88% panelists responded they “Definitely will” participate in future PEPs, thereby confirming their feasibility, with the following quote being representative of the panelists’ experience & impact “I appreciated how our input as patients was valued and highly taken into consideration. It felt like our time and feedback was important to everyone.” Conclusions: PEP constituted of pts from countries in AP&ME are feasible and lead to impactful improvements in the development of PLS and disease education information. Given pt advocates in these countries are volunteers from organisations with limited resources, have diverse backgrounds in terms of culture, language & disease awareness, their input is more representative of a broader pt population. As a result, the final versions of the reviewed documents were more inclusive & accessible. [Table: see text]
Epithelial ovarian cancer survival by race/ethnicity in an equal-access healthcare population.
Authors: Arter Zhaohui Liao , Desmond Daniel , Berenberg Jeffrey L. , Merritt Melissa A.
Published: June 2021

e18525

Background: Previous studies in the general population have observed that compared with Non-Hispanic White (NHW) women, Pacific Islander (PI) and Non-Hispanic Black (NHB) women have higher age-adjusted mortality rates from epithelial ovarian cancer (EOC), while Asian Americans (AS) have lower mortality. It is unknown whether these patterns reflect biological differences, environmental exposure or perhaps access to care. Our objective was to investigate whether self-reported race/ethnicity is associated with differences in EOC survival in a Military population where patients have equal access to healthcare. Methods: The study population included women diagnosed with EOC (ovarian, fallopian tube and primary peritoneal cancers) among US Department of Defense beneficiaries reported in the Automated Central Tumor Registry Database (year of diagnosis range: 2001-18). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models following participants from their date of diagnosis until last contact or censoring, whichever occurred first. Multivariable models were adjusted for covariates selected a priori because of their known influence on risk of EOC death; age at diagnosis (continuous), histology, stage and receipt of the first course of chemotherapy treatment. We adjusted for year of diagnosis (continuous) to account for possible changes in treatment over time. Results: The study population included 1151 patients diagnosed with EOC: 796 NHW, 111 NHB, 130 AS, 49 PI and 65 Hispanic (HS). All EOC patients had complete information on age at diagnosis, stage and chemotherapy treatment. During a median (interquartile range) follow-up of 3.5 years (1.8-6.7), 702 EOC patients (61%) died of all causes. When comparing crude EOC patient characteristics by racial/ethnic group, NHW had the highest frequency of EOC leading to death (58% vs. < 49% in other groups). There also were differences in histology; NHW and NHB had a higher frequency of serous tumors ( > 56% of EOCs vs. < 52% in other groups); PI had a high proportion of endometrioid histology (14% of EOCs vs. < 11% in others); 10% of EOCs among AS had clear cell histology (vs. < 9% in others). HS had a high percentage of local disease (23% vs. < 20% in others). In multivariable survival analysis adjusting for clinical factors, we observed that compared with NHW, there were no differences in EOC survival by race/ethnicity: AS, HR = 0.80 (95% CI = 0.61-1.05); NHB, HR = 0.96 (95% CI = 0.72-1.28); PI, HR = 0.92 (95% CI = 0.58-1.46); and HS, HR = 0.82 (95% CI = 0.56-1.21). Conclusions: We observed no racial/ethnic disparities in EOC survival in a Military equal access treatment environment. These results highlight the importance of studying how differences in access to healthcare may impact observed racial/ethnic disparities for EOC.
Measuring the impact and sustainability of a statewide program for identifying minority and underserved clients at risk for hereditary breast and ovarian cancer (HBOC): An eight-year follow up including transitions during the COVID pandemic.
Authors: Kerber Alice S. , Gabram Sheryl G. A. , Durrence Diane , Shin Janet Y. , Paris Nancy M. , Durham Lynn M.
Published: June 2021

e18546

Background: The Georgia Breast Cancer Genomics Program was created with 2011-2014 funding from the Centers for Disease Control and Prevention and the Georgia Department of Public Health (GDPH). In collaboration with GDPH and the Georgia Center for Oncology Research and Education (Georgia CORE), the goal of the program has been to reduce disparities among high-risk minority and underserved women. The objective of this study is to report the 8-year surveillance data for women at increased risk for HBOC in statewide public health centers. The effect of the COVID pandemic on the program and sustainability is also reported. Methods: From 11/1/2012-12/31/2020, the program provided education, outreach and collected surveillance data using an online genetics referral screening tool as recommended by USPSTF. Providers in 159 counties and health centers across Georgia were educated in cancer family history collection and appropriate referral to genetics. When an individual was found to be at high risk, she was referred to the Georgia CORE Genetics Advanced Practice Nurse for additional education, genetic testing and follow-up. Results: Online screenings attributable to GDPH totaled 29,087 with 1,656 positive screens. 28 % of clients were less than 25 years of age and 56 % ranged from 25-54. Race: 33 % white, 41 % black, 15 % Hispanic and 11 % other or N/A. 92 % of referrals were uninsured. Genetic testing was started or completed on 430 clients. 36 individuals declined testing after counseling (reconsideration, insurance, unknown reasons) and were provided with contact information. 47 (11%) pathogenic, clinically significant mutations were identified including 37 (79 %) HBOC related mutations and 10 (21 %) Lynch related mutations. Variants of uncertain significance were identified in 90 (21 %) clients, with multiple variants in 40 of those. 27 clients have been served through GDPH for physician consultation and surveillance. 13 were referred to area resources: one diagnosed with cancer, and 7 chose referral to other health care providers. Because of the pandemic, the program transitioned to telecommunications and remote access to testing in 5/2020. From 5/2020-12/2020, 34 clients completed testing (41% minority, all uninsured). 10 (29%) clinically significant mutations were identified and heightened surveillance initiated. Conclusions: The GDPH and Georgia CORE collaborative genomics program has served clients over the past 8 years, adjusting to changing resources while reaching a significant number of minority and underserved women. The program successfully converted to remote services during the COVID pandemic. Lessons learned from this transition have been incorporated into planning for future program sustainability.
Impact of race and socioeconomic status on breast cancer outcomes within the AJCC staging system.
Authors: Kantor Olga , Wang Monica L. , Bertrand Kimberly , Chavez-MacGregor Mariana , Freedman Rachel A. , Pierce Lori J. , King Tari A. , Mittendorf Elizabeth A.
Published: June 2021

e18565

Background: The persistent racial and socioeconomic status (SES) disparities in breast cancer outcomes are partially attributed to propensity towards more aggressive cancers or presentation at higher stages among these groups. Chronic stressors related to race and SES are another major mechanism underlying these inequities. This study aims to examine the effect of race and SES within the AJCC 8th-edition staging system, which incorporates anatomic extent of disease and tumor biology. Methods: The SEER breast cancer database linked with county-level census data was used to identify patients with invasive breast cancer from 2010-2015. The database includes a composite SES-index which was analyzed in quintiles. Cox proportional-hazards regression was used to estimate disease-specific survival (DSS). Results: 259,852 patients were included: 176,369 (67.9%) non-Hispanic white, 28,510 (11.0%) Black, 29,737 (11.4%) Hispanic, and 22,887 (8.8%) Asian. Black race, lower SES, public insurance, lower education, and increased poverty were associated with decreased DSS. Adjusted survival analysis for patient, SES, tumor, and treatment characteristics demonstrated that patients of black race had inferior DSS within each stage. Fully adjusted models also showed patients residing in lower SES counties had inferior DSS [Table]. Conclusions: Racial and SES disparities in breast cancer-specific mortality were evident across all stages of disease. Future efforts to improve breast cancer outcomes should systematically assess and address racial and socioeconomic factors as fundamental drivers of inequitable outcomes.

Adjusted 5-year DSS Estimates, Stratified by Race and SES.[Table: see text]
Mammography screening disparities in Asian American women: Findings from the California Health Interview Survey 2015-2016.
Authors: Li Yannan , Xie Hui , Theodoropoulos Nicholas , Wang Qian
Published: June 2021

e18568

Background: Foreign-born Asians were less likely to utilize preventive care due to medicine beliefs, language barriers, insurance coverage, and more. Their perceptions of breast cancer risks and screening benefits for asymptomatic conditions may differ from individuals born in the United States. It is urgent for preventive health professionals to understand screening disparities in Asian Americans. Methods: Data from the California Health Interview Survey (CHIS) 2015-2016 were used. Multivariable adjusted logistic regressions were generalized to identify the up-to-date mammography screening in relation to socioeconomic, chronic health condition/health behavior, and preventive care utilization, stratified by race. Results: Of NH-White and Asian American women aged 40 and above (unweighted N = 13,451), 78.41% were NH-White, 25.38% were foreign-born, 56.88% spoke only English at home, and 6.44% were not currently insured. The prevalence for self-reported mammography screening in NH-White and Asian American women were 68.06% and 65.97%, respectively. Among Asian American women, the lowest rate of mammograms was in Koreans (55.29%) and Chinese (72.19%) had the highest rate (p = 0.6438). In NH-White women, place of birth, smoking status, borderline diabetes, high blood pressure, is currently insured, and having a preventive care visit in the past 12 months were significant factors. Within Asian American women, borderline hypertension and having a preventive care visit were significant factors, but not ethnicity. Conclusions: The findings indicate that mammogram disparity in relation to socioeconomics, health behaviors, preventive care utilization, and race. Further development of ethnic-specific cancer prevention strategies and policies that address the subgroup differences within the larger racial/ethnic population are needed. Public health outreach and cancer education should target Asian American women with borderline hypertension and no preventive care visits.
The timeliness of lung cancer care: A systematic review of systematic/scoping reviews on time intervals and their impacts on cancer outcomes.
Authors: Zhang Jianrong , Oberoi Jasmeen , Karnchanachari Napin , Druce Paige , IJzerman Maarten J. , Emery Jon D.
Published: June 2021

e18572

Background: Lung cancer is characterized by the aggressive nature and lack of early noticeable symptoms, highlighting the importance of timely care for lung cancer. This systematic review of systematic and scoping reviews provides the summary of review-level results related to the length of time intervals and the impact of these intervals on oncological outcomes. Methods: Eligible articles included published systematic or scoping reviews and meta-analyses that used systematic searching to investigate the length of time intervals and their impact on patient survival and disease stage at diagnosis in original studies on lung cancer, based on at least one interval involving the date of diagnosis as the start/endpoint. Articles were searched via PubMed, Embase, Web of Science, and the Cochrane Library (date range: from database inception to 6 August 2020) (PROSPERO identifier: CRD42020203530). Results: From 1395 identified publications, we included a total of 8 systematic/scoping reviews published in 2002-2018 (7 on length of intervals, 5 on survival/stage impact). For the length of intervals, these reviews found that intervals across countries/medical facilities are heterogeneous and often longer than recommended by guidelines. For the survival/stage impact, the results from these reviews indicated mixed (positive, negative, or no) associations between time intervals and patient survival/disease stage at diagnosis. We further summarized study-level results and confirmed the finding of mixed associations based on 36 eligible original studies from over 100 studies included in these reviews. Methodologically, review authors pointed out large variations in time intervals (96 unique variations) and methods used to measure intervals. Based on the reviews, we found that the intervals in studies were normally investigated cross-sectionally, rather than temporarily (to demonstrate the trend of intervals’ length over time). Conclusions: Current evidence indicates that patients with lung cancer may experience diagnosis and treatment delays, however, the association results between the length of intervals and lung cancer survival and stage are paradoxical. To minimize avoidable delays, future studies should keep updating the length of intervals and provide the trend analysis of the intervals over time, as part of cancer surveillance to guide future policy making and clinical practice. To improve the quality of future original studies and systematic reviews, specific guidelines and corresponding studies related to study design and methodology (e.g. types of time intervals, measures of time intervals, statistical analysis strategy) are warranted, especially underscoring the effect of “waiting time paradox” when investigating the impact of time intervals on patient outcomes.
Graphical representations of patient tolerability data: Recommendations from the National Cancer Institute (NCI) Cancer Moonshot Standardization Working Group.
Authors: Gresham Gillian , Mazza Gina L. , Langlais Blake , King-Kallimanis Bellinda , Rogak Lauren J. ,   Patient Tolerability Consortia Standardization Working Group
Published: June 2021

e18612

Background: Effective communication of treatment tolerability data is essential for clinical decision making and improved patient outcomes, yet standardized approaches to the analysis and visualization of tolerability data in cancer clinical trials are currently limited. To address this need, the Standardization Working Group (SWG) was established within the NCI Cancer Moonshot Tolerability Consortium. This abstract describes the SWG’s initiative to develop a publicly accessible online toolkit with a comprehensive set of guidelines, references, and resources for graphical displays of tolerability data. Methods: A multidisciplinary group of PRO researchers including biostatisticians, clinicians, epidemiologists, and representatives from the NCI and FDA convened monthly to discuss toolkit development and content. Considerations for standardization of graphical displays of tolerability data included (1) types of graphical displays, (2) incorporation of missing data, (3) labeling and color schemes, and (4) software to produce graphical displays. For consistency, considerations of tolerability relied on the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE), which includes 124 items assessing the frequency, severity, interference, and/or presence of 78 symptomatic adverse events. Graphical displays were generated using simulated PRO-CTCAE data and summarized by composite score (range 0-3).Color schemes that were Section 508 compliant and color blindness accessible were created. Surveys were distributed to 68 consortium members to assess preferences and interpretability of the graphical displays. Results: The SWG created graphical displays for PRO-CTCAE data, including bar charts, butterfly plots, and Sankey diagrams and compiled SAS macros and R functions to do so. Graphical displays made available in the toolkit maximize the use of PRO-CTCAE data, incorporate missingness, support between-arm comparisons, and present data longitudinally over treatment cycles or study timepoints. Survey results for labeling and color schemes were summarized and informed a list of short labels for PRO-CTCAE items (e.g., “radiation burns” for “skin burns from radiation”) and standardized color schemes for use in graphical displays. Survey results were also summarized to provide insight into PRO researchers’ ability to accurately interpret the graphical displays. Conclusions: Standardizinggraphical displays is important for improving the communication and interpretation of tolerability data. The type of graphical display used depends on the purpose of the analysis and should be tailored to the intended audience, including patients. This toolkit will provide a comprehensive resource with best practice recommendations.
Reducing hospitalizations: Implementation of CADD pumps in infusion clinic at a Los Angeles safety net hospital.
Authors: Do Tiffanie Thy , Yeh James Jen-Chi
Published: June 2021

e18648

Background: Computerized ambulatory drug delivery (CADD) pumps introduced in the 1980s made it possible to move infusion delivery from the hospital to the home. At Harbor-UCLA Medical Center, hundreds of scheduled chemotherapy admissions occur annually. The procurement and implementation of CADD pumps was a collaborative effort with members of pharmacy, nursing, physicians and administration. The implementation of CADD pumps for home chemotherapy demonstrated a cost-savings by decreasing the number of inpatient hospital days required for scheduled chemotherapy admissions. Methods: The first outpatient chemotherapy infusion by CADD pump began on 12/5/2017. Records from 12/5/2017 through 12/4/2018 (365 days) were reviewed to assess the benefit of CADD pumps, defined by inpatient hospital days avoided. Eight chemotherapy regimens were administered through outpatient CADD pumps; the equivalent number of inpatient hospital days were estimated based on inpatient hospital records between 2015 and 2017. The average number of hospital days that would have occurred inpatient per chemotherapy regimen was multiplied by the number of outpatient CADD pump chemotherapy infusions to estimate the number of inpatient hospital days avoided. Based on information provided by our hospital’s finance department, including reimbursement for inpatient and similar outpatient care, each hospital day avoided was estimated to provide $1,695 in cost-savings. On average, a typical hospitalization for infusional 5-FU chemotherapy was three days in length. Results: Over one year, 35 patients received a total of 178 outpatient CADD infusions. The average number of CADD infusions per patient was five. We estimated that 642 hospital bed days were saved over a 1-year period following the implementation of outpatient CADD pumps. With the estimate that each hospital bed day saved was valued at $1,695, we concluded a savings of $1.1 million dollars at our hospital through the implementation of CADD pumps within the first year. Conclusions: The implementation of CADD pumps for home chemotherapy demonstrated cost-savings by decreasing the number of inpatient hospital days required for scheduled chemotherapy admissions. This shift provides a superior value for the patient with equivalent treatment outpatient, spending less time in the healthcare setting, and reduced health care costs. [Table: see text]
Transition of dose-adjusted EPOCH therapy into the outpatient healthcare setting, quality and cost considerations under an alternate payment model.
Authors: Savaya Sandra , Villanueva Joselyn , Sharif Atefeh , AlRawashdh Neda , Garcia Andrew , Abraham Ivo , Persky Daniel O , McBride Ali
Published: June 2021

e18655

Background: Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin DA-(EPOCH)-containing regimens are frequently utilized in lymphoma, however, outpatient EPOCH or modified inpatient/outpatient EPOCH has not been described extensively. We transitioned inpatient EPOCH to the outpatient setting and modified EPOCH to be given in the inpatient setting with rituximab outpatient to improve quality of care and access to patient assistance programs. Methods: A single-center, institutional review board-approved retrospective study was conducted for adults receiving EPOCH-based regimens. Data were collected by chart review for each patient between January 2013 and September 2020. The primary outcomes were to determine the incidence of chemotherapy delays due to disease-related reasons as febrile neutropenia (FN), adverse events or abnormal labs and the incidence of FN between patients receiving inpatient (IP), outpatient (OP), or combination inpatient/outpatient DA-EPOCH +/- R (hybrid). Secondary cost analysis including hospital stay cost, chemotherapy and laboratory monitoring costs was performed for the three settings. Results: A total of 43 patients received 175 cycles of an EPOCH regimen (18 [10.3%] IP), 90 [51.4%] OP, and 67 [38.3%] hybrid). The mean maximum dose level achieved with DA-EPOCH+/-R was dose level 2 with the average number of cycles at 4.1 cycles/patient. A total of 15 cycles were delayed due to disease related reasons: 1 (6%) in IP, 12 (18%) in hybrid (P = 0.196, when compared with IP) and 2 (2%) in OP (P = 0.432 when compared with IP). A total of 166 cycles received granulocyte-colony stimulating factor (G-CSF); 16 cycles (9.6%) administered IP with a FN incidence of two (12.5%), 62 cycles (37.4%) administered in the hybrid setting with a FN incidence of seven (11.3%) (P = 0.893 when compared with IP) and 88 cycles (53%) administered OP with a FN incidence of ten (11.3%) (P = 0.896 when compared with IP). The incidence of FN was 9.3% and 12.7% in patients received pegfilgrastim same day versus next day, respectively, P = 0.558. The incidence of FN in patients received reference pegfilgrastim was 9.5% vs 7.7% for patients received pegfilgrastim-cbqv in OP setting (P = 1.00). Transitioning EPOCH to a hybrid IP/OP or OP setting yielded a total cost savings to the health-system of $3,523,174 with 607 hospital bed days saved. Conclusions: EPOCH-containing regimens can be safely transitioned into the outpatient setting or utilized as a hybrid of EPCOH and outpatient Rituximab after chemotherapy side effects can be monitored and outcomes optimized, to better adapt treatment strategies for individualized patient therapies. As new healthcare payment models are developed, outpatient treatments allow for adaptive financial options both for the payor and the patient.
Improving pneumococcal vaccination rates in pediatric acute lymphoblastic leukemia/lymphoblastic lymphoma.
Authors: Chang Simone , Cheerva Alexandra , Huang Michael Angelo , McGowan Kerry , Knapp Esther E , Raj Ashok , Slone Natalie , Zhao Jun , Tse William T , Barbour Mustafa
Published: June 2021

e18666

Background: Pediatric Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma (ALL/LLy) is the most common pediatric cancer. Invasive pneumococcal disease (IPD) is prevalent in this population and the Centers for Disease Control and Prevention recommends pneumococcal vaccination to decrease morbidity and mortality. Despite these recommendations, vaccination rates remain low and the incidence of IPD among children with hematologic malignancy is significantly higher compared to the average pediatric population. An interventional study was designed to improve the vaccination rate and reduce the incidence of IPD in our institution. Methods: A plan-do-study-act (PDSA) model of quality improvement (QI) was used. Chart review at our institute was done for the 6-month period of January 2020 - June 2020 and baseline rates for pneumococcal polysaccharide (PPSV23) vaccination were calculated. Patients were included if they were ≥ 2 years old, diagnosed with ALL/LLy, and undergoing maintenance. A multidisciplinary team performed the root cause analysis. Immunization records were obtained and reviewed and targeted interventions were implemented. The interventions used are outlined in Table. The percentage of pediatric ALL/LLy patients per month in maintenance who received age-appropriate pneumococcal vaccinations was monitored before and after the interventions. Results: Analysis of the 6-month retrospective cohort (n=36) showed a baseline vaccination rate of 5.5%. During the subsequent 6-month phase with interventions, 40 patients were prospectively enrolled. Demographics showed a mean age of 10.2 years (range, 2-21) and a predominantly male (66.7%) cohort. B-cell ALL/LLy comprised the majority (78.9%); the rest included T-cell ALL/LLy and mixed phenotype acute leukemia. As seen in Table, the percentage receiving at least 1 pneumococcal vaccine increased from 5.5% to 84.8% over the first 3 months, this plateaued around 81%. Completion of the series mirrored this and increased to 74.2%. Pre-visit planning and cues proved to be the most helpful interventions. Conclusions: Use of a PDSA model successfully improved pneumococcal vaccination rates in the pediatric ALL/LLy population. We suggest these results can be achieved with planning and implementation of the outlined interventions. [Table: see text]
The efficacy and safety of oral levofloxacin therapy for overall infection prophylaxis in cancer patients with neutropenia in outpatient settings.
Authors: Davenport Lilia , Chin Jamie , Blum Sharon , Akerman Meredith
Published: June 2021

e18681

Background: Patients undergoing chemotherapy treatment are at risk for bacterial infection during their period of neutropenia. However, not all neutropenic patients are at high risk for developing infection. The purpose of this study was to evaluate the efficacy and safety of prophylactic oral levofloxacin in high, intermediate, and low infection risk patients with cancer in the ambulatory care setting. Methods: This was a retrospective chart review of 100 cancer patients with high, intermediate, and low overall infection risk who were prescribed outpatient oral levofloxacin prophylaxis between October 2019 and July 2020. This quality improvement project included adults with a history of malignancy and presence of neutropenia who have received chemotherapy treatment and oral levofloxacin therapy for overall infection prophylaxis. The primary efficacy outcome was the rate of hospital admission due to febrile neutropenia. The primary safety outcome was the occurrence of side effects of levofloxacin therapy. Secondary outcomes evaluated the duration of levofloxacin therapy, the rate of fluoroquinolone resistance in positive bacterial cultures, progression to sepsis in hospitalized patients and the rate of death due to mult-idrug resistance including fluoroquinolones. Results: Hospital admission due to febrile neutropenia after a chemotherapy cycle occurred in 18% of patients prescribed levofloxacin. Among hospitalized patients due to febrile neutropenia, 2% had low to intermediate overall infection risk and 16% had high overall infection risk. The primary safety outcome occurred in 25% of patients. The incidence of QTc prolongation occurred in 8% of patients; dermatologic side effects occurred in 9% of patients; the rate of Clostridioides difficile infection was 6%, and the rate of tendon rupture was 2%. Median duration of levofloxacin prophylaxis in the low overall infection risk group was 7 days, compared to the intermediate overall infection risk group (8.5 days) and the high overall infection risk group (14 days) with Kruskal-Wallis test p-value of 0.0009. The rate of fluoroquinolone resistance in positive bacterial cultures was 10%. Progression to sepsis in hospitalized patients occurred in 17% of patients. The rate of death due to multi-drug resistance including fluoroquinolone was 2%. Conclusions: Our findings signify preserved efficacy of levofloxacin prophylaxis in the ambulatory setting. Our findings should be considered to develop rational strategies to reduce fluoroquinolone overprescribing or limit duration of levofloxacin prophylaxis. If patients present with solid tumors and experience neutropenia, the use of antibacterial prophylaxis is not recommended because in general, patients recover from neutropenia quickly.
Real-world data analysis of the utilization of second-line maintenance therapy for patients with advanced ovarian cancer.
Authors: Reid Robert Lawrence , Xie Yiqiong , Shi Junxin , Wallace Katrine L
Published: June 2021

e18702

Background: Although ovarian cancer (OC) represents about 1% of all new cancer cases in the US, it is the 5th leading cause of cancer death among women. Several maintenance therapies have been introduced (ie, bevacizumab and poly[ADP-ribose] polymerase inhibitors [PARPi]) to extend the time between chemotherapy and relapse (ie, progression-free survival) in this population. Both bevacizumab and PARPi have been recommended as second-line (2L) maintenance treatment by the National Comprehensive Cancer Network for OC patients (pts) with and without BRCA alterations since 2013 and 2017, respectively. We present recent estimates of 2L maintenance utilization. Methods: From the iKnowMed electronic health record database of the US Oncology Network, which includes 1,200 physicians operating in over 470 sites of care in the US, adult females were included if diagnosed with advanced OC, received a 2L platinum-containing regimen for advanced OC, and had ≥2 visits within the database between 1 Jan 2016 and 31 July 2020. Pts were followed longitudinally until 31 Oct 2020, the last pt record, or date of death, whichever occurred earliest. Rates of 2L maintenance therapy (ie, bevacizumab monotherapy or PARPi following discontinuation of 2L platinum-based chemotherapy) were determined for 1) all pts, 2) pts with a BRCA1 or BRCA2 gene alteration (BRCA+), and 3) pts without a BRCA alteration (BRCA-). Results: 11,494 pts were identified with a diagnosis of advanced OC; of those, 1,051 met the study inclusion criteria. Median age at advanced OC diagnosis was 64.2 years. Median follow-up time from discontinuation of 2L platinum chemotherapy until the end of observation was 24.6 mo. Of 1,051 pts who received 2L platinum-based chemotherapy, 513 (49%) subsequently received maintenance therapy (271 [26%] PARPi, 294 [28%] bevacizumab, 32 [3%] a non-platinum chemotherapy) and 538 (51%) did not receive maintenance (ie, underwent “active surveillance”). The proportion of eligible pts receiving 2L maintenance did not increase over the study period, with 53%, 58%, and 56% of pts receiving 2L maintenance versus 47%, 42%, and 44% of pts undergoing active surveillance in the years 2017, 2018, and 2019, respectively. Among the 1,051 pts who received 2L platinum chemotherapy, 662 pts had a documented BRCA test result (94 [14%] BRCA+, 568 [86%] BRCA-). Among BRCA+ pts, 67% received 2L maintenance, while BRCA- pts received significantly less maintenance treatment (53%, p = 0.0104). Conclusions: Despite having several treatment options available for 2L advanced OC maintenance, fewer than half of eligible pts receive maintenance treatment. Although the utilization rate was higher among pts with BRCA alterations versus those without, our data suggest that there is a significant proportion of eligible pts who are not receiving maintenance therapy despite treatment guideline recommendations.