bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient navigation as an effective way to increase breast, cervical, and colorectal cancer screening among immigrants in the US: A systematic review.
Authors: Mann Katherine , Sun Kennedy , Jang Jeffrey , Khilnani Aneka , Barrett Emmalee , Harrod Thomas , Phillips Serena
Published: June 2024

e22501

Background: Immigrants undergo recommended cervical, breast, and colorectal cancer screening at a lower frequency than U.S.-born patients and face unique language, educational, and cultural barriers. The delay or lack of screening has known implications in the presentation of breast, cervical, and colorectal malignancies, including worse staging at diagnosis. To address the disparity in cancer screening that immigrants experience, various interventions have been studied, including patient navigation (PN) programs. This systematic review aims to determine whether PN increases cervical, breast, and colorectal cancer screening in immigrant populations. Methods: A systematic literature search was conducted using PubMed, Scopus, and Web of Science to identify English-language articles published from January 2000 to November 2023 examining the role of patient navigators in encouraging routine breast, colorectal, and cervical cancer screening among immigrant populations in the United States. For the articles that met the inclusion criteria, details of patient navigation programs and uptake or change in cancer screening behaviors were extracted. Results: We screened 2196 articles, 53 of which met criteria for review, and 18 articles were ultimately included in the analysis. PN programs increased breast, cervical, or colorectal screening within immigrant populations compared to the control or alternative intervention in all 18 studies. In 7 out of 18 (38.9%) studies, the PN intervention group achieved screening rates similar to or above Non-Hispanic White national average screening rates. Two of those studies occurred in the outpatient setting, which resulted in higher screening rates than community-based settings. Two of those 7 studies that matched the Non-Hispanic White screening rates also had a longer duration of over 4 years. The majority of PN programs included educational sessions or materials and screening appointment scheduling assistance delivered from members of the same cultural group. Other services included identification and assistance with overcoming barriers, insurance assistance, reminders, transportation, and accompaniment to screening appointments. Of the 18 studies included, rural areas were underrepresented, and the training of patient navigators was not always described. Conclusions: Our review suggests that PN programs are effective at increasing cancer screening rates among immigrant populations, and certain aspects of PN programs, including outpatient settings and longer navigation duration, may help to further increase screening rates.
Analysis of diagnosis patterns and implications on cancer stage in patients with lung cancer: A single-institution experience.
Authors: Zafar Maha , Arnous Muhammad , Nwankwo Nkolika , Reddy Aswanth
Published: June 2024

e22508

Background: Lung cancer is the most common cause of cancer-related death in the US. Patients are often diagnosed at advanced stages, challenging treatment and improving life expectancy. There has been tremendous progress in developing newer treatments; however, it is crucial to emphasize low-dose CT (LDCT) screening as it may improve earlier diagnosis and ultimately lead to better outcomes. Research Question What is the utilization of LDCT for lung cancer screening in newly diagnosed lung cancer patients? Do patients with lung cancer diagnosed after LDCT have earlier-stage disease when compared to patients who did not have LDCT? Methods: We conducted an observational cohort study on all new lung cancer patients seen in our clinic from January 2022 to July 2023 (18 months). Data collected included the age, type of lung cancer (NSCLC/SCLC), reason and method of initial identification of lung mass/nodule, methodology of biopsy, cancer stage, and if the patient was eligible for LDCT. Results: Over the study duration, 143 newly diagnosed lung cancer patients were seen in our oncology clinic. Of these, only 12% (18) patients had LDCT before diagnosis. Amongst these 18 patients, 44% (8) were diagnosed with stage I, two patients were diagnosed with stage II, and 44% (4+4) were diagnosed with stages III and IV. A total of 56% of patients (combined stage I/II) were eligible for curative treatment in this group. The remaining 82% of patients were diagnosed with lung cancer after imaging for other reasons (non-LDCT group). In this group, the most common stage at diagnosis was stage IV, constituting 39% (56) of the patients, followed by patients diagnosed at stage III with 24% (34). Only 37% (combined stage I/II) were eligible for curative treatment in this group. Conclusions: The USPSTF recommends annual lung cancer screening with LDCT for adults aged 50 to 80 years who have a 20-pack-year smoking history and are current smokers or have quit within the past 15 years. In an observational study conducted in 2021 from our institution, we identified a lower utilization of LDCT in eligible patients. We improved the screening rates by more than 50% from baseline with lung navigation intervention. In this study, we show that patients are getting diagnosed with lung cancer from X-rays and CTs performed for reasons including but not limited to chest pain, shortness of breath, workup for pulmonary embolism, and preoperative X-rays. Most patients diagnosed after LDCT (44%) had stage I disease compared to only 18% of patients in the non-LDCT group. We also observed that a significantly higher percentage (56% vs 37%) of patients are eligible for curative treatment (stage I/II) when diagnosed with LDCT. We highlight the importance of LDCT screening potentially offering a curable treatment in patients with lung cancer.
Recruitment strategies in a lung cancer screening program for Asian women with no smoking history.
Authors: Li Wenyuan , Bell Jaimie , Shum Elaine
Published: June 2024

e22514

Background: The Female Asian Nonsmoker Screening Study (FANSS) is a pilot study for eligible Asian women with no smoking history to provide low-dose CT (LDCT) Chest scans for lung cancer screening annually for 3 years. To recruit for the study, we took into consideration several factors including potential language barriers, low awareness of lung cancer incidence in non-smoking populations, and participant (pt) availability. Here we describe the use of various recruitment strategies to support enrollment to the FANSS study. Methods: Multimodal recruitment strategies for enrollment into FANSS were used. A dedicated phone line answered by receptionists able to speak English and several Chinese dialects was created. Research staff are bilingual or utilized telephonic interpretation services in all pt interactions. Informational flyers available in both English and Chinese were mailed to primary care physicians serving primarily Asian communities and posted in pharmacies and storefronts in NYC Chinatown. A website was developed for interested individuals to submit their contact information for further information. Working with our institutional Epic EMR, a list of all pts with active MyChart accounts was created with criteria “Asian,” “female,” “OK to contact for Research recruitment,” “age 40-74,” and excluded anyone with a smoking history and “Cancer” in the past 5 years. From this list, pts then were sent an IRB-approved recruitment message through MyChart from 3/2023-6/2023. Interested pts who reached out through the above methods were contacted by research staff to determine eligibility. All eligible pts who agreed to participate were consented either in-person or virtually to allow for schedule flexibility to review the consent. Results: From 3/5/21 to 1/27/24, 1518 women inquired about FANSS through our website, dedicated phone line or MyChart messages and were directly contacted by our team. After determination of eligibility, 760 pts had an informed consent discussion either virtually or in-person. From 3/5/21 to 3/2023, 247 pts underwent the consent process and 229 pts had a baseline LDCT. Following the intervention of directed MyChart messaging in 3/2023, 568 pts responded to the MyChart message indicating interest, however 102 pts were not eligible due to inaccurate info in their Epic medical record (i.e. ethnicity or smoking history). Overall, from 3/2023 to 1/27/24, 513 pts underwent the consent process. Among these, 90 subjects (18%) were recruited via MyChart. Conclusions: Recruitment to a lung cancer screening program in non-smokers is feasible, and specific considerations tailored to engage minority populations can improve enrollment such as bilingual staff and translated materials. The use of directed messaging through the Epic EMR is an important tool to identify potential pts which may be applied to aid in recruitment to other clinical trials or lung cancer screening programs.
The effect of advances in management of uterine-serous-carcinoma on population mortality.
Authors: Wang Aifen , Hou Shunyu , Feng Ninghan , Hu Weidong , Zhang Yayun , Xu Jiaqi
Published: June 2024

e22516

Background: Incidence and mortality of uterine cancer has reported to be declining. However, mortality trends of endometrial serous carcinoma remain unclear at a population level. Methods: We applied SEER to evaluate uterine-serous- carcinoma mortality and relevant deaths of this disease to incident cases. We assessed trends of population mortality based on specific causes and races. Incidence of uterine serous carcinoma were evaluated based on ethics and calendar year. Trends of incidence and incidence-based mortality were evaluated by Joinpoint software. Results: Incidence of uterine serous carcinoma decreased by 1.51% from 2000 through 2017, followed by increase of 16.58% from 2017 through 2019. Mortality of women with uterine serous carcinoma due to uterine serous carcinoma decreased by 4.33% annually from 2000 to 2010, and then decreased at a rate of 1.88% every year from 2010 to 2017, and then sharply declined by 44.69% from 2017 to 2019. Mortality of women with uterine serous carcinoma due to other causes increased by 0.94% annually from 2000 to 2016, and then increased at a high rate of 35.18% every year from 2016 to 2019. Incidence-based mortality of women with uterine serous carcinoma due to other causes increased by 39.03% annually from 2000 to 2004, and then increased at a rate of 2.93% every year from 2004 to 2019. Incidence-based mortality of patients due to other causes showed similar pattern. Patients’ incidence-based mortality due to uterine serous cancer increased at rates of 111.02% and 9.80% annually from 2000 through 2002, from 2002 through 2006 respectively, followed by a decrease of 3.87% annually from 2006 through 2019, and then a gradual increase of 6.55% annually from 2002 through 2005. Incidence of white patients with uterine serous cancer decreased at a rate of 4.42% from 2000 through 2017 and then increased by 21.61% from 2017 through 2019. Incidence of Asians patients presented similar pattern. However, incidence of Black patients increased at a rate of 0.93% from 2000 through 2015 and then sharply increased by 8.49%. Incidence-based mortality of white patients with uterine serous cancer increased at a rate of 105.16% from 2000 through 2002, and then increased by 10.93% from 2002 through 2006, followed by a decrease of 3.40% from 2006 through 2019. Incidence-based mortality of Black patients elevated at a rate of 114.03% from 2000 through 2002, and flatten out, increased by 1.94% from 2002 through 2019. Incidence-based mortality of Asian patients showed similar pattern. Conclusions: Declined incidence-based mortality from 2006 through 2019 may associate with management advances of uterine serous carcinoma. Decreased incidence-based mortality of White patients with uterine serous carcinoma from 2006 through 2019 and increased incidence-based mortality of Black patients and Asian patients with uterine serous carcinoma in same period may related to better management resource of White patients.
Patterns and trends in incidence, survival, and treatment among patients with early-onset lung cancer in the U.S.: A population-based study.
Authors: Li Wang-Zhong , Liang Hengrui , Liu Jun , Wang Wei , Huang Ying , Lao Shen , He Miao , Liang Wenhua , He Jianxing
Published: June 2024

e22517

Background: Lung cancer is the second leading cause of cancer-related deaths among young adults. An in-depth investigation into the demographic distribution and temporal trends in early-onset lung cancer (EOLC) incidence and survival, as well as treatment patterns, could help monitor the cancer burden, identify high-risk populations, and develop effective screening and prevention strategies. Methods: This serial cross-sectional study used data from the U.S. Cancer Statistics (USCS) and the Surveillance, Epidemiology, and End Results (SEER) program. EOLC refers to lung cancer diagnosed in individuals aged 20-49 years. USCS database (2001-2019) was used for demographic description and incidence estimation. SEER-17 registries database (2000-2019) was used for survival estimation and treatment patterns examination. Age-adjusted incidence rate per 100,000 population and cancer-specific survival were reported. Changes in rates were assessed with average annual percentage change (AAPC) using Joinpoint regression. Results: There were 4,086,435 lung cancer cases recorded between 2001 and 2019 in the U.S. (USCS: 53.3% male; median age of 70 years). EOLC accounted for 4.1% (169,132) of all lung cancer cases and was more common among females, non-Whites, with higher adenocarcinoma and advanced-stage diagnoses. During this period, the incidence of EOLC decreased from 9.0 to 4.5 per 100,000 population (APC, -4.2; P < 0.001). EOLC incidence continued to decrease across all demographic groups, except for young people aged 20-29. The rate of decline was faster among men than women, blacks than whites, squamous carcinoma than adenocarcinoma, and distant disease than localized disease. The historical higher incidence among young men vs. young women and among blacks vs. whites have been reversed in recent years. A consistent increase in survival rates of EOLC across all demographic groups from 2001 to 2017 (SEER-17) was observed. Despite the increases were more pronounced among men than women and among black individuals than white individuals, gender and racial disparities persisted. EOLC patients received more intensive treatment than late-onset patients. Still, 12.1% of EOLC cases were not treated, and this was most common among black individuals and those with distant disease. Treatment patterns for EOLC have not undergone significant changes in recent decades. Of note, the proportion of untreated patients has not decreased during the study period. Conclusions: EOLC was an uncommon type of disease with distinctive clinical features in the U.S. Substantial decreases in incidence and improves in survival were observed, whereas major treatment pattern remained relatively stable.
Examining the epidemiology of AIDS-defining and HPV-associated cancers in HIV endemic areas of south Florida for development of targeted intervention.
Authors: Leavitt Antonia Pryor , Lee Ming , Nahodyl Lauren , Krenz Till , Kobetz Erin N.
Published: June 2024

e22522

Background: The Miami-Dade and Broward Counties in South Florida (SF) have the highest incidence of HIV infection in the United States, with over 47,000 people living with HIV as of 2021. The epidemiology and burden of cancers associated with HIV in SF have not been fully described, hampering efforts for effective cancer control. This study examines the regional epidemiology of AIDS-defining cancers and HPV-associated cancers, for which HIV+ patients face higher risk. The results are used to develop education and community screening events targeting communities with high incidences of these cancers. Methods: The catchment area of Sylvester Comprehensive Cancer Center, consisting of Miami-Dade, Broward, Palm Beach, and Monroe Counties for a total population of six million was studied. Using the 2015-2019 data from Florida’s official cancer registry, age-adjusted incidences (AAI) for AIDS-defining cancers and HPV-associated cancers were calculated for all census tracts in SF. Geospatial hot spot analysis was then applied to identify statistically significant clusters (hot spots) of census tracts with high AAI of these cancers. Results: We identified two clusters of hot spots for AIDS-defining and HPV-associated cancers in SF. Except for penile cancer in one cluster, both clusters have HPV-associated cancer incidences that are significantly higher than the state averages. Specifically, one cluster has the highest incidence of anal cancer in SF, while the other has a notable concentration of penile cancer. Conclusions: Using the results, we have developed targeted educational and screening events for communities within the hot spots. A screening summit was recently held in a hot spot community where several screening and educational events were offered on a single day. By sharing information about the epidemiology of these cancers, we were able to facilitate community buy-in and develop working relationships with community partners to provide culturally competent and targeted intervention for a population who are less likely to undergo screening. [Table: see text]
Prevalence of HTLV-1 and 2 infection in the blood donor population of Colombia during 2012 to 2022.
Authors: Molina Jaime , Triana Ivan Camilo , Segovia Javier
Published: June 2024

e22528

Background: The HTLV-1 and 2 virus are oncogenic retrovirus with a global distribution. Viral infection is primarily associated with two conditions: HTLV-1-associated myelopathy and adult T-cell lymphoma. Although Colombia is an endemic country for the virus, data on its incidence, prevalence, and the population characterization of infected individuals are limited. Methods: This is a descriptive observational study of a retrospective cohort from a blood donor population of Fundación Hematológica de Colombia from 2012 to 2022, to determine the seroprevalence of HTLV-1 and 2 in this population. Demographic and clinical variables such as age and gender were described to characterize the seropositive population and identify specific populations, such as women of childbearing age who are seropositive for the virus. Results: During the study 1,553,478 patients were recruited, of which 3,484 were seropositive, representing a global prevalence of 0.22% over 10 years. The annual incidences were as follows: from 2012 to 2013, 0.22%; from 2014 to 2015, 0.26%; 2016 to 2017, 0.23%; 2018 to 2019, 0.25%; 2020 to 2021, 0.15%; and in 2022, 0.12%. Among the seropositive individuals, 58% were women, and 42% were men. In the donor population studied, the order of prevalences by city was as follows: Bogotá with 48%, Ibagué 13%, Barranquilla 7%, Pasto 5%, Villavicencio 4%, Pereira 3%, Soacha 3%, Tunja 2%. The average age for seropositive women and men was 22 years. 54% of seropositive women were within the reproductive age. Conclusions: Our cohort has a higher seroprevalence compared to North America. In Colombia, the two cities with the highest prevalence are the capital of the country and the city of Ibagué in our study. From a public health perspective, it is noteworthy that approximately 1100 seropositive women for HTLV-1 and 2 are in reproductive age and could potentially transmit the oncogenic virus through vertical transmission or breastfeeding. With our results it would be in the interest of public health agencies to report positive results to women of child bearing age and positive donors to begin health counseling as soon as possible.
Knowledge, attitudes, and practices of university students towards risk factors, screening, and perceived barriers of screening regarding colorectal cancer: A multi-country study from the eastern Mediterranean region.
Authors: Tarhini Zeinab , Christou Niki , Jost Jeremy
Published: June 2024

e22543

Background: Colorectal cancer (CRC) tends to be diagnosed at a younger age and at a more advanced stage. Knowledge and awareness of CRC and its screening in Middle East are suboptimal, and most countries lack national screening programs. Our objective was to assess the knowledge, attitudes and practices of university students regarding risk factors, screening and perceived barriers to CRC screening in Middle Eastern countries. Methods: A cross-sectional study using a convenience sampling method was done in different universities across ten Middle Eastern countries: Lebanon, Iraq, Syria, Palestine, Egypt, Jordan, Saudi Arabia (KSA), and others (Qatar, United Arab Emirates, Kuwait). Data were collected using a questionnaire shared with students in various universities. It comprised five main sections: socio-demographic characteristics, CRC knowledge, risk factors, symptoms and screening, attitudes, practices and barriers related to CRC screening. The questionnaire developed on the basis of a literature review, was properly translated and validated using factorial and reliability analysis. Results: A total of 4597 students participated in the study with a mean age of 24.28 ± 7.62 years. Participants’ countries of residence were Lebanon 1107 (24.1%), Jordan 811 (17.6%), Iraq 769 (16.7%), Palestine 478 (10.4%), Syria 450 (9.8%), Saudi-Arabia 438 (9.5%), Egypt 499 (10.9%) and others 45 (1.0%). Most participants had heard about CRC (87%). 2491 (54.2%) had first or second -degree relatives diagnosed with cancer. 84.2% of participants intend to undergo CRC screening in the future, however, 25.1% wouldn't pay for the screening if it is not covered by health insurance. The majority of students demonstrated good knowledge of CRC (96.5%), with Egypt demonstrating the highest level (98.2%), followed by Lebanon (97.1%) and Iraq (97.1%), and Jordan the lowest (94%). Factors associated with good knowledge were age (aOR = 1.03; 95%CI: 1.00-1.05), health-related studies (aOR = 2.80; 95%CI = 2.00-3.93), and the participant’s country of residence. The most important barrier to CRC screening in Lebanon was the lack of financial resources with high cost of test (52.6%), lack of health insurance in Syria and Jordan (50.4% and 49.3% respectively), poor counseling from doctors in KSA (52%), and the inadequacy of awareness campaigns in Iraq (57.1%), Egypt (56.1%) and Palestine (55%). Conclusions: Students in the Middle East demonstrate good knowledge of CRC. Nevertheless, they perceive barriers to CRC screening, including limited financial resources, high cost of tests not covered by health insurance, and inadequate awareness campaigns.
Leveraging real-world data from multiple institutions to assess the rate of bilateral mastectomy after cancer genetics evaluations with genetic counselors.
Authors: Daley Ashley , Russell Callan , Stuhlmiller Timothy Joseph , Kaufman Zachary , Davies Jill , Caleshu Colleen
Published: June 2024

e22551

Background: Genetic counselors (GCs) assess patients’ risk of cancer and counsel them on cancer screening and preventative measures, based on national guidelines. Prior studies have found that adherence to guideline-based care is higher after genetic counseling. Thus care provided by GCs leads to a variety of imaging and surgical services that can both improve patient outcomes and generate revenue for health systems, which can in turn help financially support cancer genetics programs. Research that quantifies such downstream services and revenue is lacking. We aimed to address this gap by using real-world data from multiple institutions to quantify the rate of bilateral mastectomies occurring after cancer genetics evaluations performed by GCs. Methods: We studied consecutive patients from a nationwide telehealth practice who underwent genetic counseling and cancer risk assessment with a GC after having germline genetic testing. Structured data obtained from multiple care sites via health information networks and manual chart review of electronic medical records was utilized to determine whether patients had bilateral mastectomies after the GC appointment. Results: Of the 460 consecutive patients seen by a GC, 30 were advised to consider bilateral mastectomy, based on their genetic test results and national guidelines. Data was available from the health information networks for all (29/29 (100%)) of these patients who live in the United States, with a mean follow-up of 2.7 years (SD 0.23). These 29 patients had a mean age of 43.3 years (SD 15.3), were all female, and carried mutations in BRCA2 (18/29 (62%)), BRCA1 (6/29 (21%)), or PALB2 (5/30 (17%)). Clinical data was collected from 468 locations, a median of 23 unique locations per patient. At the time of the GC appointment, 7/29 (24%) had active breast cancer, 19/29 (66%) were unaffected, and 3/29 (10%) had a history of previously treated breast cancer. Two patients were diagnosed with breast cancer after the GC appointment. 15/29 (52%) patients underwent bilateral mastectomy after the GC appointment, including most patients with active breast cancer (7/9 (78%)), 8/17 (47%) unaffected patients, and none (0/3 (0%)) with a previously treated breast cancer. Among those without breast cancer, the mean time from the GC appointment to the bilateral risk-reducing mastectomy was 8.6 months (SD 4.4). Conclusions: Half of patients who had bilateral mastectomy indicated because of their genetic test results elected to have mastectomy done after discussion of this guideline-based care option with a GC. As evidenced in prior research, bilateral mastectomy markedly reduces risk of breast cancer. In addition to improved patient outcomes, the revenue a health system receives from these surgeries can also help to support cancer genetics services.
Baseline surveillance in Li Fraumeni syndrome using whole-body MRI: A systematic review and meta-analysis.
Authors: Dacoregio Maria Inez , Reis Pedro Cotta Abrahão , Celso Davi Said Gonçalves , Escalante Romero Lorena , Altmayer Stephan , Vilbert Maysa , Ynoe de Moraes Fabio , Gomy Israel
Published: June 2024

e22555

Background: Li-Fraumeni syndrome (LFS) is a cancer syndrome associated with early-onset neoplasias. Risk management through a routine cancer surveillance strategy is critical. Since patients with LFS are susceptible to radiation-induced cancers, the use of whole-body MRI (WBMRI) is recommended for regular cancer screening. However, the guidelines for clinical management and the evidence supporting the benefits of WBMRI surveillance in asymptomatic LFS patients are limited. Therefore, this systematic review and meta-analysis assessed the clinical utility of WBMRI in germline TP53 mutation carriers at baseline and at follow up. Methods: We systematically searched Pubmed, Cochrane, and Embase libraries for studies evaluating WBMRI as an early detection method for tumor screening in patients with LFS. We pooled the prevalence and presented the overall rate with 95% confidence intervals (CI) of the individuals found to have one or more investigable lesions, the lesions found to be new cancers among suspicious lesions, and the individuals with one or more new cancers among the total population. Statistical analysis was performed using R software version 4.3.1 and heterogeneity was evaluated with I2 statistics. Results: From 1,547 initial studies, 11 (10 observational cohort and 1 case control) comprising 703 patients (359 females [51%]; mean [SD] age, 29.5 [+/-25] years) were included from 7 different countries. Median follow-up of lesions ranged from 2 to 11 years. We found an estimated detection rate of 31% (95% CI 28-34, I2 55%) of any suspicious lesions in asymptomatic TP53 carriers who underwent baseline WBMRI was found. In total, 277 lesions that required clinical follow-up in 215 patients were identified. Cancer was confirmed in 46 lesions in 39 individuals. Most of the cancers found were Central Nervous System (CNS) tumors (n = 16), followed by sarcomas (n = 12) and breast cancer (n = 11). The estimated cancer diagnosis rate among suspicious lesions was 18% (95%CI 13-25, I2 5%). WBMRI detected 41 of 46 cancers in the early disease stage, with an overall detection rate of 6% (95% CI 5-8, I2 47%). Incidence rate was 2% per patient-round of WBMRI (95% CI 1-4, I2 0%), including baseline plus follow up. Conclusions: Our systematic review and meta-analysis supports that surveillance with WBMRI is effective in detecting cancers in patients with LFS. Additionally, WBMRI surveillance was successful in diagnosing almost 90% of cancers in early-disease stage, which increases the chances os cure in this young population.
Statistical fragility of findings from randomized phase 3 trials in pediatric oncology.
Authors: Olsen Hannah , Kao Pei-Chi , Richmond Caleb , Shulman David Stephen , London Wendy B. , DuBois Steven G.
Published: June 2024

e23003

Background: The fragility index (FI) and survival-inferred fragility index (SIFI) have been proposed as adjunctive metrics to facilitate interpretation of p-values in clinical trials. FI/SIFI is the number of patients on a positive (p < 0.05) trial’s experimental arm who would need to switch from “responder/non-event” to “non-responder/event” to cause p > 0.05. Fragility indices have been reported previously in medical oncology, with median values < 10 often seen in the literature. This metric has not been studied in pediatric oncology trials. Methods: PubMed was used to identify randomized phase 3 pediatric oncology trials published between 1980-2020. We report trial characteristics and calculate FI for trials with a binary outcome and SIFI for trials with a time-to-event outcome. We also report the fragility quotients (FQ and SFQ) to normalize FI and SIFI relative to trial size. Results: 113 trials included sufficient data for analysis. The median FI for trials with a binary outcome (n = 40) was 4.5 (range: 1-33). The median SIFI for trials with a time-to-event outcome (n = 73) was 13 (range: 0-61). The FI or SIFI was less than the number of patients lost to follow-up in 25% of 36 trials. Median FQ = 0.026 and SFQ = 0.03, indicating that revised outcome in 2.6% or 3% of trial participants would be sufficient to alter the trial conclusion. FQ and SFQ did not significantly vary according to trial characteristics. While sample sizes increased over time (mean 187, 1980s; mean 437, 2010s), FQ and SFQ remained stable between 2-3%. Conclusions: The statistical conclusions of pediatric oncology phase 3 trials hinge on a relatively small number and proportion of patients. Despite sample size limitations of low prevalence diseases, pediatric cancer trials appear similarly or less fragile than adult oncology trials. Fragility was similar for large versus small trials and remained constant over four decades. [Table: see text]
Double reading performance and the impact of adjudication on progression-free survival estimations: Findings from a lung clinical trial.
Authors: Beaumont Hubert , Iannessi Antoine
Published: June 2024

e23010

Background: The FDA recommends Blinded Independent Central Review (BICR) with double read for clinical trials with imaging. However, inter-reader variability is a concern in these trials. While studies have investigated the variability of RECIST, the primary response criteria, little attention has been given to the optimal association of readers. The evaluation of therapeutic response in phase III trials relies on the Date of first Progressive Disease (DoPD), with the Discrepancy Rate (DR) as the preferred index for measuring inter-reader variability in DoPD evaluation. Another important index measures readers' bias, assessing their tendency to over or under-estimate diagnoses. In cases of discrepancies, a third reader is brought in for adjudication. However, the impact of adjudication on trials' Progression-Free Survival (PFS) is not well-documented. Our study examines the variability in a lung clinical trial using RECIST, analyzing double reading performance, reader association prediction, and the impact of adjudication on PFS estimations. Methods: We retrospectively analyzed five phase III lung clinical trials using the RECIST 1.1 criteria in BICR with double reads. The trials involved 7 readers organized into 11 teams, each reader having participated in multiple trials and performed over 50 reads, resulting in 1017 patients' reviews. Our analysis included: Calculation of DR and bias for each team, and testing the correlation between DR and bias. Computation of the signed bias for each individual reader. Evaluation of a probabilistic model to predict the DR for each team and the bias for each reader. Comparison of PFS between single and double reads after adjudication and endorsement of one of the readings. Results: A multiple comparisons test did not reveal any difference between teams’ DR (Marascuilo test; q > 0.05). The average DR across all teams was 39.9% [95%CI; 37.8; 41.9]. However, we did find significant differences in bias when comparing 9/55 pairs of teams (Marascuilo test; q < 0.05). The range of absolute bias values was 20% to 100%. We did not find a correlation between bias and DR (p = 0.64). Additionally, when comparing the average bias value per reader, no differences were observed (Marascuilo test; q < 0.05). We failed to predict teams DR and readers' bias. The endorsement rate of readers ranged [18%; 82%]. After adjudication, we found that 27% of the PFS were lower than the minimum value obtained from the single readers, in one case 20.6% shorter. Conclusions: Significant readers' bias has a notable impact on double readings, independent of the DR values. The performance of one reader cannot be generalized based on others. Additionally, adjudication significantly affects the PFS of clinical trials. These findings emphasize the importance of considering readers' bias and the potential consequences of adjudication in clinical trial assessments.
Utility of automated data transfer for cancer clinical trials.
Authors: Altomare Ivy , Shelley Addison , Lu Yichen , Salcuni Paul M. , Graves Nicole , Maiti Abhishek , Govindan Ramaswamy
Published: June 2024

e23011

Background: The burden of data collection on site staff for cancer clinical trials is steadily increasing, and inefficiencies in data entry into electronic data capture (EDC) systems lead to poor data quality and delays in reporting. Software that facilitates automated transfer of mapped structured data from the electronic health record (EHR) to the study EDC system can help to address these challenges. We examined the impact of multi-site usage of an embedded point and click EHR-to-EDC tool on study data capture across multiple cancer clinical trials. Methods: We conducted a retrospective analysis of usage of an EHR-to-EDC tool among research teams at 3 Academic Medical Centers (AMCs) for 4 industry-sponsored Phase 1 cancer clinical trials from the start of use of the tool at each AMC to a cutoff date of 12/31/23. We assessed the types and volume of structured data accessible via FHIR APIs and amenable for transfer (“mapped”) across protocols, the volume of data transferred per protocol, and the time for data transfer, defined as time from case report form (CRF) launch to submission in EDC and time spent in the software application overall. Descriptive statistics were generated for all study metrics. Results: During the 10 month observation period, the EHR-to-EDC tool was used by 8 users to transfer data for 25 patients enrolled across the 4 protocols. Table 1 shows the percentage of total CRF forms mapped and breakdown of proportion of mapped fields per protocol. Overall, 8,597 individual data points (87% labs, 10% vitals and 3% concomitant medications) were pushed for 718 unique CRF submissions. The average number of individual data points and unique CRF submissions per patient were as follows: 400 and 36 (Study A), 420 and 36 (Study B), 251 and 16 (Study C), 270 and 21 (Study D). The average total time spent in the tool per CRF submission was 2.16 minutes (range 1.17-7.00 minutes, inclusive of potential inactive time, application launch and data search). The average time to complete a CRF was 46 seconds (range 15-65 seconds). Conclusions: Use of EHR-to-EDC software facilitated efficient automated transfer of a high volume of study data due to EDC-required repeat use of mapped CRF forms. The impact appeared consistent across protocols, with dozens of unique CRF submissions and hundreds of individual data points pushed per patient for each study. Time for CRF completion was low and uniform across users. This study supports the growing adoption of EHR-to-EDC technology among sites and sponsors, and highlights the evolving potential to further improve and facilitate clinical trial data entry, as tool capabilities are developed beyond structured fields to enable unstructured data capture and transfer. [Table: see text]
A prospective double-blind clinical study: Effect of probiotics and thalidomide on radiation enteritis in patients with pelvic cancer undergoing concurrent chemoradiotherapy.
Authors: Jiang Chunling , Xu Xiaoyan , Wang Xin , Yi An , Li Bin , Li Jingao , Zhang Huaiwen
Published: June 2024

e23013

Background: Radiation induced diarrhea (RID) is one of the commonest and most distressing side effects during and after radiotherapy predominantly in patients whose irradiation region is pelvis. Thalidomide reduces severity as well as the frequency indicated in RID but mechanism of action is not elucidated. Probiotics are beneficial microorganisms that may regulate flora of intestines to increase immunity and have a protective effect on RID. This pilot study was designed to ascertain effects of thalidomide and probiotics on RID in patients being subjected to pelvic irradiation. Methods: A double-blind, single-center, randomized pilot study was conducted. Patients were classified into two groups as thalidomide plus probiotics (Lactobacillus rhamnosus + Probio-M9, ) group (TP group) or plus placebo group (P group).Incidence of grade 3/4 diarrhea, was a primary endpoint of the study. Other secondary endpoints analyzed were rates and severity of diarrhea, antibiotics use, body weight, albumin, and lymphocyte changes. 31 patients undergoing pelvic radiotherapy with or without concurrent chemotherapy were randomly selected from government tertiary general hospital. Results: The incidence of grade 3/4 diarrhea was 9.5% (95% CI: 0 to 24.5%) in TP, which was significantly different from historical data of 30% to 60%. The incidence of grade 3/4 diarrhea in group P was 19.8% (95% CI: 0~41.3%). The frequency and severity of diarrhea in group TP were little less than in group P. There is no significant difference between them. Basically, the time for antibiotic use in groups P and TP was the same, with a slightly longer time from first antibiotic exposure in group TP as compared to group P. The moment of first antibiotics have been prescribed in our study patients, this was better than that of a clinical routine treatment experience and other research data according to the literature. The changes in body weight, albumin level, and lymphocyte at different stages before and after radiotherapy in group TP were not statistically significant, and the level of body weight and albumin in group P was slightly reduced compared with before radiotherapy but increased compared with group TP after radiotherapy. Furthermore, there were no severe adverse effects regarding thalidomide as well as probiotics reported among patients who participated in this study. Conclusions: The combined treatment with thalidomide and probiotics is beneficial to ameliorate RID in patients receiving pelvic radiotherapy, yet this study can't represent whole conclusion due to small size of patients. We will also need larger, multicenter double-blind placebo-controlled trials to confirm exact efficacy and safety of this combined treatment. Clinical trial information: NCT05059613 .
Cancer screening and first-time visits to oncology services during and after COVID-19 pandemic in Uruguay.
Authors: Delgado Lucia Beatriz , Camejo Natalia , Castillo Cecilia , Vacca Nicolas , Camargo Bruno , Krygier Gabriel David
Published: June 2024

e23016

Background: On March 13, 2020, Uruguay confirmed the first cases of COVID-19 and the same day the government declared a Public Health Emergency that was extended until April 4, 2022. The measures implemented to mitigate the transmission included, among others, postponing screening studies and in-person consultations. Added to these measures was the fear of going to health centers and the consequences of the economic crisis, with the increasing difficulties in traveling and facing the co-payments necessary to access health services. This study aims to evaluate the impact of the COVID-19 pandemic on cancer screening and first time- visits to oncology services during the public health emergency and following its lifting. Methods: We compare the number of PAP test, mammograms and fecal immunochemical test (FIT) reported by the same comprehensive health providers during 3 periods: pre-pandemic (2018-2019), public health emergency period (March 13, 2020- April 4, 2022) and post-public health emergency (April 5 2022-June 30,2023). Cancer screening data was obtained from the screening registry of the Honorary Commission to Fight Cancer (CHLCC) and first oncology visits from the Oncology Electronic Health Record (HCEO). Health providers that report PAP, mammograms, and FIT cover around 90%, 30%, and 40% of health system users, respectively, and those that use HCEO, 40%. Results: After two years of COVID-19 public health emergency, the number of reported PAP smears test, mammography and fecal occult blood test, decreased by 26%, 46% and 33% respectively (Table 1). The reduction was greater during the first months of the pandemic and during the peak of the first wave (April-June 2021: PAP -50%, mammography -58%, occult blood test: -70%). Likewise, the number of first-time visits to oncology services decreased by 37%, reaching a 56% decline during the first wave. As shown in Table 1, these declines continued after the health emergency was lifted. Conclusions: Our results show an important decline of cancer screening and first-time visits to oncology services during the pandemic in Uruguay. After emergency was lifted, reported PAP test showed a partial recovery but mammography, occult fecal blood test and first-time visits to oncology services remain well below pre-pandemic levels. [Table: see text]
Pilot study to evaluate automated laboratory data transfer into Medidata Rave for NCI-supported pediatric cooperative group trials in the Pediatric Early Phase Clinical Trials Network (PEP-CTN) and Pediatric Brain Tumor Consortium (PBTC).
Authors: Miller Tamara P. , Aplenc Richard , Minard Charles G. , Wang Yu , Lensing Shelly , Velamuru Prasanna , Foster Jennie Haunani , Silverman Milena , Sung Cheryl , Wong Karina , Beeles Thalia Angelica , Weigel Brenda , Onar-Thomas Arzu , Fox Elizabeth
Published: June 2024

e23017

Background: Electronic data capture (EDC) has the potential to improve data accuracy and efficiency. As an initial step toward improvement in the accuracy and completeness of data acquisition for clinical trials, PEP-CTN and PBTC conducted a pilot project to assess the feasibility of automated transfer of laboratory data from participating institutions’ electronic health records to the NCI Medidata Rave EDC that is housed within each consortium’s Uniform Resource Locator (URL). The pilot aimed to assess feasibility of automated laboratory data extraction and transfer and to evaluate discrepancies between laboratory data obtained retrospectively through automated extraction and data manually ascertained during the original conduct of the study. Methods: Data from patients treated on 7 completed PEP-CTN or PBTC trials at 7 sites were included. Each consortium created a Rave EDC study to receive data. Sites used the ExtractEHR R package or local methods to map and extract laboratory data for designated patients. Post-extraction data were uploaded via a file transfer protocol (FTP) periodically polled by the Rave Batch Uploader (BU) that uploaded data into Rave EDC. After successful upload, extracted data (EHR) were compared to laboratory data that had been manually reported when patients were enrolled on the trials (MANUAL) and discrepancies were identified. Discrepancy types were categorized and 2 sites reviewed discrepancies at their sites to identify reasons. Results: Preparation and support for automated extraction and upload required significant central operations and local site effort. All sites successfully extracted specified laboratory data and had at least one complete upload via BU to Rave EDC. There were more laboratory data in the EHR datasets than MANUAL datasets across most sites. These results were due to multiple EHR results on a given day or from additional days in the study window than specified in MANUAL. Sites verified that laboratory data in MANUAL and not EHR were stored in un-extractable formats (e.g. PDFs) or outside laboratories. Most discrepant results in both EHR and MANUAL were mismatched values or units. Conclusions: This pilot demonstrated the feasibility of implementing automated laboratory data extraction and transfer in the cooperative group setting. Automated data transfer requires significant central operational support as well as detailed protocols, data specifications, and case report forms and engagement of site technical teams to be successful, but also permits collection of more comprehensive data with reduced manual data entry. Clinical trial information: NCT05020951 .