bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analytical and clinical validation of a circulating tumor DNA–based assay for multicancer early detection.
Authors: Tran Le Son , Nguyen Luu Hong Dang , Nguyen Hanh Thi-Hue , Nguyen Duy Sinh , Tang Hung Sang , Giang Hoa , Nguyen Hoai-Nghia , Phan Minh-Duy 
Published: June 2024

10548 Background: The development of multi-cancer early detection (MCED) through a single blood test has emerged as a promising method for improving the efficiency of early cancer detection and benefiting population health. However, the lack of analytical validation and clinical evidence for their utility in diverse populations have prevented their use in clinical practice. To address these challenges, we conducted a comprehensive analytical and clinical validation for an MCED test, SPOT-MAS (Screening for the Presence of Tumor by DNA Methylation and Size). Methods: A prospective cohort study (ClinicalTrials.gov identifier: NCT05227261) was conducted at 13 major hospitals and one research institute in Vietnam. Our study recruited asymptomatic participants aged 40 years or older and followed up for 6 and 12 months. Analytical sensitivity of our assay was assessed by using our healthy and cancer-standard samples with known tumor fraction. The clinical performance was assessed by computing the positive predictive value (PPV), the negative predictive value (NPV) and accuracy in detecting tumor tissue-of-origin (TOO). Results: SPOT-MAS demonstrates the capability to detect at least 50% of cancer samples with a specificity of 98% when the samples have a tumor fraction of 0.049 (95% CI: 0.043-0.059). These results were consistently reproduced in both intra- and inter-batch analyses. Furthermore, our test maintains robustness even in the presence of hemoglobin contamination up to 500 mg/dL and genomic DNA contamination of up to 100%. Our analysis of 10,027 eligible participants demonstrated its ability to detect cancers in asymptomatic individuals with a positive predictive value of 58.14% (95%CI: 43.33- 71.62), an accuracy of 84.00% (95%CI: 65.35-93.60) in predicting tumor location and a negative predictive value of 99.92% (95%CI: 99.83-99.96). Conclusions: To our knowledge, this is the first and largest prospective validation study in Asia supporting the utility of SPOT-MAS as a multi-cancer blood test for early detection in a low- and middle-income country, where a nationwide cancer screening program is urgently needed but currently not available. Clinical trial information: NCT05227261 .
Cervical cancer screening in 48000 females over two decades: Feasibility and success of community-based screening in Kerala, India.
Authors: Pai D. Krishnanadha , Bhat B.V. , Gangadharan Harsha , Panda Pankaj Kumar , V C Ravindran , Das Roy Lopamudra , Mullapally Sujith Kumar 
Published: June 2024

10550 Background: Cervical Cancer is still significant cause of mortality and morbidity among females in India. Various methods of cancer screening are currently practiced for cervical cancer prevention including human papilloma virus (HPV) screening, pap smear, visual inspection with Lugol’s iodine (VILI), visual inspection with acetic acid (VIA) etc. The success of any cancer screening method is based on the feasibility of large-scale implementation at community level and the scientific validity of the screening test. VIA/VILI has been proven to prevent mortality in cervical cancer. This study is based on analysis of prospectively maintained database of community based cervical cancer screening using VIA/VILI in northern Kerala from 2002 to 2020. Methods: Retrospective analysis of prospective database of cervical cancer screening from 2002 to 2020 done by Malabar Cancer Care Society in Kerala, a non-governmental organization with support from governmental bodies like ISRO. Data was collected into excel sheets and were rechecked. The data on demography, type of screening, detection of precancerous and cancerous lesions was analyzed. Descriptive statistics were used to analyze the data using SPSS Version 20.0. Results: A total of 48008 individuals were screened over 18 years. 55% were premenopausal. 33% were fully asymptomatic and remaining 66% had white discharge per vaginum (25%), bleeding per vaginum (14%) or combination of symptoms (25%). 18% had abnormal per speculum findings (bleeds on touch, discharge etc.) 86% had unhealthy cervix.26% (12650) had VIA/VILI and 74% (35658) had pap smear. The pap smear findings were normal (41%), atrophic (17%), inflammatory (40%) and 2% had pre-cancerous/ cancerous changes. Of these lesions, 46% were HSIL, 36% were LSIL, 5% ASUS and 13% were squamous cell carcinoma (52 cases). Screen positive rate was 325 (0.005%) out of 48008. Treatment of precancerous lesions was by Cryotherapy (54%), LEEP (10%) and Surgery (36%). Treatment of invasive carcinoma was by surgery (91%) and radiation (85%). Referral to regional cancer center was done in 26% patients. The screen positive rate shows decreasing trend over the last two decades. Conclusions: Cervical Cancer screening in large scale in low resource setting is feasible in India by both pap smear and VIA/VILI with community based interventions led by NGO with support from governmental bodies. This model can be considered ideal for India and other low middle income countries with logistic difficulties for large scale HPV based screening.
Evolving burden of lung cancer attributable to occupational carcinogens in 38 OECD countries: Global, national differences, age dynamics and implications for global health.
Authors: Lakkimsetti Mohit , Vanodia Mihir Paresh , Singh Kushagrita , Goel Shrey , Bathvar Pinank , Patel Dhruval Pinalkumar , Vemparala Priyatha , Patel Juhi , Amin Vishrant , Koyani Himanshu Bharatkumar , Gadhiya Dhruvkumar , Desai Hardik Dineshbhai 
Published: June 2024

10576 Background: Lung cancer (LC) remains a predominant cause of global mortality and disability, particularly significant in Organization for Economic Cooperation and Development (OECD) nations. Understanding the evolving burden of LC attributable to occupational carcinogens (OC) is critical due to its prevalence in occupational settings. Methods: Employing a standardized approach from the Global Burden of Disease study, we estimated deaths and disability-adjusted life years (DALYs) caused by lung cancer linked to OC. Our analysis spans age, gender, year, and location across the 38 OECD countries from 1990-2019. Results were presented as absolute counts and age-standardized rates (ASR) per 100,000 person-years, with projections extended to 2040 using regression frameworks. Results: Deaths from LC attributable to OC increased from 120,862 (95%UI: 91,114-148,937) in 1990 to 167,917 (127,888-208,066) in 2019, with DALYs rising from 2.4 million (1.8-3.1) to 2.9 million (2.2-3.6) over the same period. The United States recorded the highest number of deaths (41,075), followed by Japan (20,496) and the United Kingdom (15,223) in 2019. Notably, the Netherlands exhibited the highest age-standardized mortality rate (ASMR) at 12.62 cases per 100,000, with Belgium and the United Kingdom following closely. Asbestos exposure accounted for the highest number of deaths (147,263), followed by silica (15,660), arsenic (3,172), and diesel engine exhaust (2,798). Males bore a significantly higher burden than females over the last three decades, with the 75-79 age group recording the highest number of deaths (32,477) and the 70-74 age group registering the highest DALYs (613,442). Conclusions: The study underscores the escalating burden of LC attributable to occupational carcinogens across OECD countries, highlighting the imperative for robust preventive measures and targeted interventions. Urgent action is warranted to mitigate exposures to known carcinogens in occupational settings, particularly among vulnerable populations, to curb the escalating public health challenge posed by occupational lung cancer.
Barriers to implementing clinical cancer genetics in sub-Saharan Africa: Perspectives of participants of a virtual cancer genetics course.
Authors: Fadelu Temidayo , Manirakiza Achille Van Christ , Uwineza Annette , Uwinkindi Francois , Koeller Diane R. , Rebbeck Timothy 
Published: June 2024

10597 Background: While clinical cancer genetics remains underutilized in sub-Saharan Africa (SSA) and many low-middle income countries, there are few empiric studies assessing knowledge gaps and perspectives of healthcare providers. We conducted a survey of participants of a virtual short course ( https://www.africanoncogenetics.org/home ). Methods: The comprehensive survey, partly adapted from other published instruments, included multiple-choice knowledge and practice questions on cancer genetics, Likert-scale questions on perspectives, and open-ended questions on barriers. Cancer genetics experts reviewed the survey to ensure face-content validity. The online course was given between October and November 2021; participants were invited through snowball circulation on global oncology listservs. Data were summarized with descriptive analysis. Results: There were 370 participant responses included in this analysis. Participants represented 40 countries, with largest representation from Nigeria (n=106, 29%), South Africa (n=50, 14%), and Uganda (n=39, 13%). Participants represented various medical specialties and research domains: laboratory medicine (15%), medical genetics (14%), biomedical science (10%), general practice (9%), and oncology (8%) were the most common. Participants also represented a spectrum of practice settings, with the highest proportions from national hospitals (29%) and private hospitals (8%). Most of the participants 223 (71%) had some genetics lectures during medical/nursing school or other training, but only 116 (37%) had attended any continuing medical education (CME) activities in cancer genetics since starting practice. Moreover, the overwhelming majority 95% expressed interest and willingness to attend a future CME course. Many participants, 148 (47.2%) rated their knowledge of cancer genetics as poor or very poor, 150 (48%) as fair, while only 15 (5%) rated as good or very good. Most participants 196 (62%) considered themselves not qualified to interpret results of clinical cancer genetics testing, 100 (32%) were somewhat qualified, and 19 (6%) very qualified. Many participants 93 (30%) noted cancer genetics testing was not available to their patients; another 67 (22%) noted testing was only available outside the country; and only 47 (15%) had testing available within their primary institutions. In aggregate, the most common listed perceived barriers to implementing cancer genetics testing were costs (18%), lack of testing infrastructure (17%), lack of personnel (17%), and lack of provider knowledge (16%). Conclusions: Our survey demonstrates several perceived gaps limiting clinical cancer genetics testing implementation in SSA. A multi-pronged approach that addresses testing costs, testing infrastructure, and patient and provider education is urgently needed.
Second neoplasms in patients with hereditary retinoblastoma.
Authors: Corral Dolores , Escudero Adela , Rodriguez Salas Nuria , San Roman Sonsoles , Peralta Jesus , Izquierdo Elisa , Feliú Jaime , Perez Martinez Antonio 
Published: June 2024

10620 Background: Patients with hereditary retinoblastoma have an increased risk of developing second tumors during adolescence and adulthood. The incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the leading cause of death in these patients. This risk is increased in patients who have received external radiation therapy as part of treatment but is also increased in non-radiated patients. Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established. Methods: We present a cohort of patients with hereditary retinoblastoma assessed in our multidisciplinary pediatric and adult genetic predisposition cancer unit (UPGeCI) from September 2018 to December 2023. During this period, 62 patients with retinoblastoma were attended, all with RB1 gene mutation. Of these, 84% of patients had bilateral retinoblastoma, and 16% had unilateral retinoblastoma. They ranged in age from 6 months to 55 years (median 13 years). 18 patients (29%) were treated with external beam radiation therapy. Clinical follow-up and orbital magnetic resonance imaging were performed every two years. Results: Six cases of SMNs were detected in 5 patients (9.3%), all soft tissue sarcomas. The mortality rate was 60% (3/5 patients). Four patients (80%) had received external radiotherapy as part of the treatment of retinoblastoma. Three patients presented 3 sarcomas in the facial region within the irradiated area, of which one was an osteosarcoma and the other two leiomyosarcomas. Two of them presented in adulthood, and one at 9 years old. One of the patients died, the other two are living disease-free. The fourth patient who had received external radiotherapy presented with osteosarcoma of the femur at 15 years of age. She died of septic shock. The patient who had not received external radiotherapy presented with osteosarcoma of the tibia at 6 years of age and later with osteosarcoma of the contralateral femur at 10 years of age. She died of progression. Conclusions: There is an increased risk of SMNs in patients with hereditary retinoblastoma, mainly soft tissue sarcomas, with high mortality. This risk increases if they have received external radiation therapy. Therefore, screening for SMNs is essential for of follow-up in patients with heritable retinoblastoma.
An AI-assisted navigation approach for patients with radiographic suspicion of new pancreas cancer.
Authors: John Kristen M. , Tenner Joseph , Croocks Rolando , Valente Cristina , Bingham Bernadette , Habowski Amber N , McEvoy Tara , Zavadsky Tiffany , Beyer Kristen , Mercieca Rita , Nadella Sandeep , Carvino Anthony , Barish Matthew , King Daniel 
Published: June 2024

11002 Background: The traditional cancer care paradigm relies on passive referral streams, resulting in suboptimal care delivery. Here, we assessed the results of an AI-assisted navigation approach to proactively coordinate specialty cancer care services for patients with radiographically suspected pancreas cancer. Methods: A natural language processing (NLP) classifier was trained to identify radiology reports suspicious for pancreas cancer from imaging reports generated within Northwell Health. The daily workflow consists of the following: the NLP flags reports with suspicion of pancreas cancer, a coordinator validates the finding, a GI oncologist and navigator coordinates specialty oncology and tumor board referral, and a clinical research coordinator pre-screens for research studies. Patients determined to be hospice-bound or with non-PDAC malignancy are excluded. Care delivery metrics were compared by Mann-Whitney U tests. Results: Prior to implementation, patients with new suspicion of pancreas cancer at our institution experienced a mean of 22 days to biopsy, 32 days to oncology visit, and 56 days to treatment initiation from radiology report with 17% referred to pancreatic multidisciplinary clinic (PMDC). Per monthly average, 1.8 patients were approached for biospecimen studies, 1.5 were consented, and 0.9 were enrolled. In the month following implementation of the AI-assisted navigation pilot, reports from 1666 patients were flagged, resulting in 38 patients with new suspicion of pancreas cancer identified (Table). Of these, 53% underwent biopsy, 50% were seen by an outpatient oncologist, 29% were referred to PMDC, and 42% received treatment at our institution. From date of radiology report, these patients underwent biopsy at a mean of 7 days (p<0.01), outpatient oncology visit at 15 days (p=0.285), and treatment initiation at 34 days (p=0.3479). A monthly average of 4 patients were approached for biospecimen studies, 4 were consented, and 3.2 were enrolled. Conclusions: An AI-guided navigation workflow identified patients earlier in the diagnostic timeline; reduced time to biopsy, follow-up, and treatment initiation; increased patient referrals to PMDC; and tripled participation in biospecimen studies at our institution. [Table: see text]
Prescription drug monitoring program mandates and opioid prescriptions received by patients dying of cancer.
Authors: Bao Yuhua , Zhang Hao , Pinheiro Laura C , Hu Allison Ju-Chen , Portenoy Russell K. , Bruera Eduardo , Reid M. Carrington , Tamimi Rulla M. , Zhang Fang , Paice Judith A. , Rosa William E. 
Published: June 2024

11003 Background: Strong consensus supports opioid analgesics as first-line pain management for patients with poor prognosis cancer approaching the end of life (EoL). State legislations that mandate prescriber access of Prescription Drug Monitoring Programs (PDMPs) when prescribing opioids intend to mitigate unsafe opioid prescriptions but may have unintended consequences in restricting access to opioids for patients dying from cancer. This study seeks to assess associations between state implementation of comprehensive PDMP mandates –applicable to all prescribers and all clinical settings and not allowing prescriber discretion – with opioid prescriptions received by patients dying of cancer. Methods: We used SEER cancer registry linked with Medicare fee-for-service claims to identify 184,123 Medicare beneficiaries 66 years or older who died of cancer in 2011-2019 in one of 10 SEER states with an operating PDMP by the beginning of 2011. We measured opioid prescriptions dispensed to patients near the EoL, defined as 30 days prior to death or hospice admission. We exploited staggered implementation of comprehensive PDMP mandates and assessed the association of such implementation with opioid prescriptions dispensed to patients near the EoL. We estimated logistic regressions for dichotomous outcomes and Generalized Linear Models for continuous outcomes. Results: Implementation of comprehensive PDMP mandates was associated with a reduction in the rate of 1 or more opioid days near the EoL from 47.2% to 45.2% (difference, 0.02 [95% CI, -0.027, -0.012]), a reduction in the rate of 1 or more long-acting opioid days from 15.8% to 14.7% (difference, 0.011 [95% CI, -0.016, -0.006]), and a reduction of 130.8 (95% CI, -161.5, -100.2) in total morphine milligram equivalents (MMEs) and of 135.6 (95% CI, -215.1, -56.1) in MMEs from long-acting opioids among patients who received 1 or more days of opioids/long-acting opioids. Conclusions: Comprehensive PDMP mandates were associated with 4-9% reduction in opioid prescriptions dispensed to patients at the EOL. Specific strategies are needed to effectively exempt patients with active cancer from such mandates. [Table: see text]
Payor denial after prior authorization request for long-acting pain medication: Provider and patient perspectives.
Authors: Chino Fumiko , Persaud Sonia , Jinna Sankeerth , Ghazal Lauren Victoria , Salz Talya , Thom Bridgette 
Published: June 2024

11004 Background: For patients with cancer, uncontrolled pain can reduce quality of life, lead to treatment breaks, and result in worse cancer outcomes. Guideline-concordant treatment for chronic, severe pain can include long-acting opioid formulations. Pain medications, however, often face prior authorization (PA), which requires providers to obtain payor pre-approval and may result in delayed or denied care. This analysis characterizes PA-related denials for pain medications for patients with cancer. Methods: At an urban comprehensive cancer center, we identified all PA requests for outpatient long-acting opioid (i.e., buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, tapentadol) prescriptions from 2023 and described frequency of PA approvals and denials. For denials, chart review 2 weeks post-PA was conducted of provider notes and patient communications with results summarized qualitatively. Results: 1752 new long-acting opioids prescriptions for 982 unique patients required PA. Of those, 1567 (89.4%) were approved after PA process, 99 (5.6%) were denied, 81 (4.6%) were cancelled after PA initiation, and 6 (0.3%) were unresolved. Most were prescribed by pain specialists including supportive care (n = 699, 40.0%) and anesthesia/pain medicine (n = 444, 25.3%) with most common indication: “Neoplasm related pain (chronic)” (61.1%). Oxycodone was the most common long-acting opioid requiring PA (n = 551, 31.4% of prescriptions), followed by fentanyl (n = 501, 28.6%), hydromorphone (n = 205, 11.7%), and methadone (n = 137, 7.8%). Long-acting morphine was denied most frequently (16.3% of n = 129 PA requests denied), followed by buprenorphine (12.1% of n = 33), and hydromorphone (7.3%). Fentanyl was denied the least (2.8%). The 99 denials affected 62 unique patients, including a patient with 7 denials. Chart review (n = 62) of the 2 weeks post-denial revealed a median of 2 (range 0-8) provider notes mentioning pain or PA barriers and median of 1 (range 0-5) patient calls or messages about the same. 22.6% (n = 14) patients ended up in the ER or admitted to the hospital for pain crisis or failure to thrive. Providers documented poor pain control, weight loss, need to “try and fail” other medications, and noted 11.3% (n = 7) patients ending up paying out of pocket for their medications. Patient messages document uncontrolled pain and unmanageable side effects with some literally begging for relief; one patient spoke of their fear of “dying in pain”. Conclusions: The vast majority of PA requests for long-acting pain medication result in approvals, suggesting that the process -which can delay essential pain management- is largely unnecessary. For the 1 in 20 requests that were denied, provider and patient concerns highlight the negative impact of uncontrolled pain. An improved, transparent PA process is essential for adequately treating chronic, cancer-related pain.