bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer risk and characteristics in older female BRCA1/2 mutation carriers.
Authors: Ghimire Bipin , Karki Ujjwal , Shrotriya Shiva , Rangarajan Tara , Zakalik Dana 
Published: June 2023

10610 Background: Cancer risk and characteristics in older females with BRCA1/2 mutations are less well studied, and the role of risk-reducing strategies in this population remains unclear. Methods: From a database of 1070 female carriers of BRCA1/2 pathogenic (PV) or likely pathogenic variants (LPV) seen at Nancy and James Grosfeld Cancer Genetics Center in Beaumont Health from January 2006 to December 2021, we identified 283 females who lived to age 65 or older. We analyzed cancer risk and clinical characteristics, focusing on females with cancer diagnosed at age 65 or older. Results: Of the 283 BRCA1/2 carriers, 229 (81%) had a cancer diagnosis, out of which 84 (37%) were diagnosed at age 65 or older. Of all the breast cancer diagnoses (n = 173), 45 (26%) were diagnosed at age 65 or older. Among these 45 patients, median age at diagnosis was 69 years (65-87); majority were BRCA2 carriers (62%), with invasive ductal carcinoma (80%), ER-positive (58%), PR-negative (55%), HER2-negative (97%), high grade (55%) and had stage I or II disease (78%). Fifteen patients (38%) were triple-negative. A minority (32%) received adjuvant chemotherapy, 43% received adjuvant endocrine therapy, and 54% received adjuvant radiation. During a median follow-up of 205 months for all breast cancers (n = 173), there were 52 recurrences, 28 of these (54%) were diagnosed at age 65 or older, of which 13 were contralateral (median time to recurrence: 140 months); 5 were local/regional (median time: 186 months) and 10 were metastatic (median time: 76 months). Ten of the 13 contralateral recurrences (77%) were in BRCA1 carriers. Of the ovarian cancer diagnoses (n = 69), 27 (39%) were diagnosed at age 65 or older. Among these 27 patients, median age at diagnosis was 71 years (65-87); majority were BRCA2 carriers (74%), had serous carcinoma (84%), with stage III or IV disease (96%). Of all ovarian cancers (n = 69), there were 15 recurrences (22%), 9 of them (60%) were diagnosed at age 65 or older. Of the 8 pancreatic cancers, 6 were diagnosed at age 65 or older. Of the 283 BRCA1/2 carriers, 249 still had at least one breast at the time of genetic testing, and 34% elected for risk-reducing mastectomy (RRM). Of the 177 patients with intact ovaries, 71% opted for risk-reducing salpingo-oophorectomy (RRSO). Compared to BRCA carriers with cancer diagnosed under age 65, a smaller proportion of those diagnosed at age 65 or older opted to undergo RRM (26% vs. 40%) or RRSO (67% vs. 78%). Conclusions: Our study reveals that female BRCA1/2 mutation carriers over age 65 continue to retain a significant risk of cancer, including breast, contralateral breast, ovarian, and pancreatic cancer. This finding supports the importance of continued high-risk surveillance and risk-reducing interventions in this growing demographic. Further studies are needed to better define the cancer risks and optimal management of older females with BRCA1/2 mutations.
Perceived mental and physical health in patients with common cancers: A study using the PROMIS framework in All of Us database.
Authors: Mohamed Salih Rajaa , Eun Yong , Olusoji Rahman Adesoji , Osei Noah , Ahluwalia Meena 
Published: June 2023

10619 Background: The self-perception of one's mental and physical health (MH and PH) is of utmost importance for individuals diagnosed with cancer. This study focuses on the assessment of self-perceived mental and physical health (MH and PH) in individuals diagnosed with cancer. The Patient-Reported Outcomes Measurement Information System (PROMIS) framework is used to measure health outcomes, with PROMIS-PH measuring physical well-being and PROMIS-MH measuring mental health status. The study aims to evaluate self-reported mental and physical health of individuals with common cancers in the All of Us database, which includes over 414,000 participants in the US who have completed PROMIS-PH and PROMIS-MH surveys. Methods: We included participants from All of Us dataset version 6, which includes survey data collected between May 6, 2018 and January 1, 2022 who had available electronic health records data (N = 258,188). From the survey data, we calculated PROMIS-PH and PROMIS-MH score in participants with diagnosis code (ICD9/ICD10) of any cancers (N = 36377), breast (N = 5172), prostate (N = 5234), colon (N = 2366), and lung cancer (N = 2338). The study compared scores each cancer groups using Wilcoxon rank sum test, with a significance level of P < 0.05. Analysis was performed in the web-based platform Jupyter Notebook using programming language R. Results: The study calculated PROMIS-MH and PROMIS-PH scores based on two questions, with response options valued from 1 to 5. The higher the score, the higher the level of perceived mental and physical health. Results showed that the mean PROMIS-MH score for all cancers was 7.38, with the highest score of 7.67 in prostate cancer and the lowest score of 7.10 in lung cancer. The mean PROMIS-PH score for all cancers was 7.31, with the highest score of 7.62 in prostate cancer and the lowest score of 6.71 in lung cancer. Prostate cancer group showed the highest PROMIS-PH and PROMIS-MH scores among the four cancer groups (P < 0.05), while participants with lung cancer reported the lowest PROMIS-PH and PROMIS-MH scores (P < 0.05). Additionally, breast cancer had higher PROMIS-MH and PROMIS-PH scores compared to all cancers (P < 0.05), while lung cancer had lower PROMIS-MH and PROMIS-PH scores (P < 0.05). There was no significant difference in PROMIS-MH score between all cancers and colon cancer. Conclusions: These results suggest that individuals with lung cancer may have a lower level of perceived mental and physical health compared to those with other cancers. Further research is needed to understand the underlying causes of these differences and to evaluate the effectiveness of interventions aimed at improving the well-being of individuals with cancer.
Clinical and social importance of follow-up assessment of family members of patients with BRCA mutations.
Authors: Nascimento Ivana Lucia de Oliveira , Freitas Juliana Cortes , Bomfim-Palma Thais Ferreira , Rodrigues Juliana Lima Gomes , Melo Thamara Ferreira , Oliveira Pollyanna Carozo , Landeiro Luciana , Meyer Roberto , Toralles Maria Betania , Lopes Taisa 
Published: June 2023

10621 Background: The identification of BRCA1 and BRCA2 genes mutations are of paramount importance in the treatment and follow-up of hereditary cancer patients. When a pathogenic variant (PV) is identified in one of these genes, the surveillance for new primary tumors becomes individualized. When a pathogenic mutation is identified other family members may also be at high risk for developing tumors. Then the investigation should become familiar. Methods: This study reports the experience of a public oncogenetics service with the identification and follow-up of relatives of patients with BRCA mutations. Of the 1505 patients registered, 773 are probands, of which 71 had a mutation in one of the BRCA genes. A total of 503 family members were evaluated, with an average of 13 relatives per proband. Results: Of the 353 relatives with a BRCA1 mutation, 132 had the familial mutation, and only 18 had cancer diagnosis. The mean age of the evaluated family members was 37 years, lower than the mean age at diagnosis of the probands, which was approximately 41 years, two founder mutations in BRCA1 (NM_007300.4:c.3331_3334del and NM_007300.4:c.211A > G) were more recurrent among index cases, which is associated with the ancestral background of the local population. For the BRCA2 gene, 148 family members were evaluated, of which 77 had a mutation and 23 had a previous cancer diagnosis. The mean age of family members evaluated for BRCA2 mutation was 43 years, similar to the mean age at diagnosis of the proband: 41 years. The NM_000059.4:c.1389_1390del and NM_000059.4:c.7124T > G variants was the most frequent in BRCA2. Conclusions: This data reinforces the importance of genetic counseling and testing of family members when a pathogenic variant is identified in a cancer patient. It is clear that early initiation of surveillance protocols, with screening and prophylactic surgeries are very effective tools for those high risk patients, they just have to be early diagnosed with the PV to benefit from this strategies. In addition, this assessment helps in understanding the mutational profile of the population in order to improve the planning of services in oncogenetics.
A scalable approach to democratizing cancer risk stratification: One healthcare system’s approach using a patient-facing digital platform.
Authors: Fecteau Heather , Kurbegov Dax , Patel Reena Manhar , Keller Haley , Horton Carolyn , Hoang Lily , Kieran Shannon M. 
Published: June 2023

10622 Background: Access to genetic testing and risk stratification is primarily gated by referrals from non-genetics providers for patients who meet testing criteria. The majority of Americans seek care at community hospitals that are closer to home; community hospitals are faced with the challenge of how to democratize access to precision oncology and cancer prevention. Research has shown that the establishment of such protocols is challenging, requiring organizational buy-in, capital, resources, and the involvement of multiple levels of clinical and nonclinical stakeholders. Here we highlight Sarah Cannon, the Cancer Institute of HCA Healthcare, and their programmatic approach to risk stratification using a digital platform offered universally to all patients undergoing screening mammography. Methods: From February to November in 2022, fourteen sites were assessed to have appropriate provider and facility capabilities to support the implement the CARE program. The web-based risk-stratification tool is sent to individuals before standard ambulatory appointments to assess their lifetime risk for breast cancer based on the Tyrer-Cuzick (version 8.0) risk algorithm and National Comprehensive Cancer Network (NCCN) genetic testing criteria. Testing criteria included hereditary breast, ovarian, pancreatic, and prostate cancers, Lynch syndrome, and familial adenomatous polyposis (FAP). Retrospective data was pulled from patients seen between February 2022 through January 2023. The outcome measures included percentage of individuals who completed the risk-assessment, met genetic testing criteria, pursued germline genetic testing, received a positive germline result, and/or had a breast cancer risk ≥20%. Results: During the 10 months at the 14 community hospitals a total of 25,671 individuals were invited for risk assessment through the CARE program; 19,277 (75.1%) individuals completed assessment. Overall, 5,070 (26.3%) met genetic testing criteria and 1,536 individuals had a ≥20% lifetime risk of breast cancer, for a total of 34% of patients identified as elevated risk. 23.4% (1,187) of those meeting criteria opted to proceed with germline genetic testing. An additional 126 individuals who did not meet criteria pursued genetic testing. Of the 1,313 completed genetic tests, 96 (7%) had positive genetic test results. Fifty-four of 96 (56%) positive results had an impact on medical management and cancer prevention. Conclusions: Sarah Cannon and HCA Healthcare have successfully begun implementing a comprehensive, digital risk stratification program in the community hospital setting to provide standardized access to genomic testing and risk stratification. By identifying patients with an elevated risk for cancer, the potential for increased early cancer detection and precision oncology can be observed in a scalable and sustainable program.
Newly diagnosed lung cancer in hospitalized patients during the COVID-19 pandemic: How well are LDCTs utilized?
Authors: Assis Jonathan , Neerukonda Thanuja , Farooqi Bilal , Haider Mahvish 
Published: June 2023

10624 Background: Medicare covers the cost of lung cancer screening in individuals aged 50-77 years with a high-risk smoking history. The COVID-19 pandemic caused a decrease in outpatient visits and cancer screenings. The objective of this study was to provide a comparison between the multitude of lung cancer diagnoses upon presentation to the hospital predating and during the COVID-19 pandemic in patients with varying insurance types. Methods: We retrospectively reviewed fifteen hospitals in West Florida with newly diagnosed lung cancer during the pre-pandemic period from March 2019-August 2020 and the pandemic period from March 2020- August 2021. These patients were split into subcategories based on insurance type: private medical insurance; Medicare; Medicaid; no insurance; and other. The chi-square test was used for statistical analysis. Results: A total of 1409 inpatients, 676 during the pre-pandemic and 733 during the pandemic, were identified with a new diagnosis of lung cancer upon presentation to the hospital. 74% of the pandemic population and 77% of the pre-pandemic population were patients insured with Medicare. Hospitals without LDCT screening programs were found to have 317 lung cancer diagnoses during the pre-pandemic period and 292 during the pandemic period. Hospitals with LDCT screening programs were found to have 359 lung cancer diagnoses during the pre-pandemic period and 441 during the pandemic period. Chi-square tests comparing pre-pandemic to pandemic did not show a p-value of statistical significance. Conclusions: A substantial number of patients with Medicare were newly diagnosed with lung cancer during the pre-pandemic and pandemic periods compared to patients with other insurance types. Although Medicare provides LDCT screening for lung cancer in high-risk populations at no out-of-pocket cost, about 75% of West Florida’s patients were diagnosed with lung-cancer upon presentation to the hospital. Hospitals with LDCT screening programs had an increase in cancer diagnoses during the pandemic, consistent with prior research data. Instead, the pandemic did not seem to affect hospitals without LDCT screening programs. We need to address the barriers in implementation of LDCT hospital-based screening programs to increase early diagnoses and decrease hospitalization diagnoses, leading to improved lung cancer mortality. [Table: see text]
Immunogenicity after COVID-19 vaccination in patients with solid tumor and hospital staff: A prospective single-center observational study.
Authors: Katsuya Yuki , Yoshida Tatsuya , Yazaki Shu , Yagishita Shigehiro , Nakahama Hiroko , Kobayashi Osamu , Yanagida Masatoshi , Irino Yasuhiro , Hamada Akinobu , Yamamoto Noboru 
Published: June 2023

10626 Background: Patients with tumor are at high risk of severe COVID-19, and vaccination against SARS-CoV-2 is recommended. Impact of cancer treatment on immunogenicity has not been evaluated well. Methods: This prospective study was conducted to assess the seroconversion rate of SARS-CoV-2 vaccines among patients with cancer and hospital staff. Further, we focused on the difference among cancer treatment regimens. SARS-CoV-2 spike protein-specific IgG (S-IgG) were evaluated before the first vaccination, 1–3 months, 4–6 months, and 7–12 months after the second vaccination, and 1–3 months after the third vaccination. The primary endpoint was seroconversion rate measured 1–3 months after the second vaccination. Results: From April 2021 to November 2021, consent was obtained from 629 cancer patients and 210 hospital staff. Excluding missing data and withdrawal of consent, 590 cancer patients and 183 hospital staff without complications was analyzed. At 1–3 months after the second vaccination, S-IgG antibody concentration higher than the cut-off value (20 BAU/mL) was found in 96.1% (567/590) patients with cancer and 100% (183/183) of the healthy controls (p = 0.0024). At 4–6 months after second vaccination, S-IgG antibody concentration higher than the cut-off value was found in 93.1% (461/495) patients with cancer and 100% (170/170) of the healthy controls (p < 0.0001). The significant difference in seroconversion rate between the two groups persisted even after 7-12 months. Patients undergoing treatment regimens such as platinum combination therapy (median: 423.7, 95% CI: 264.2–767.0, p = 0.003) and alkylating agent (median: 57.5, 95% CI: 5.4–748, p < 0.0001) among cytotoxic drugs, and PARP inhibitor (median: 264, 95% CI: 43–690.4, p = 0.0004), mTOR inhibitor (median: 227.4, 95% CI: 5.7–323.4, p = 0.0036), BCR-ABL inhibitor among drugs (median: 124.4, 95% CI: 0.0–288.9, p = 0.005) among target molecule drugs showed lower antibody titer compared to the no-treatment patients with cancer group. Conclusions: SARS-CoV-2 vaccine immunogenicity was low among patients with cancer compared to healthy control. Also, several treatment regimens were found to negatively impact immune response. Clinical trial information: UMIN000049403 , UMIN000049430 . [Table: see text]
AI to characterize patients with lung or ovarian cancer and those with cachexia for discovery of undiagnosed, misdiagnosed, and miscoded patients at scale in a privacy-preserving manner.
Authors: Guo Yike , Zhang Jingqing , Burda Marcin , Falakaflaki Parastoo , Sharma Atri Vivek , Gupta Vibhor 
Published: June 2023

10627 Background: Discovering undiagnosed, misdiagnosed or miscoded patients is critical to ensure suitability for clinical care pathways and for maximizing clinical trial recruitment. Meta-data (e.g. ICD) and generic NLP based approaches fall short due to: lack of scalability, significant miscoding of patient records and searching a pre-empted list of features without understanding their context or relationships between them. This study addresses these limitations through the application of Pangaea’s novel AI product (PIES) to characterize patients, which has discovered 4x more undiagnosed, misdiagnosed and miscoded patients in a scalable and privacy-preserving manner. Methods: PIES was configured on 235 clinically validated lung, ovarian and cachectic cancer patient records from secondary care. First, PIES determines all concepts which are reflected in a patient’s record based on a medical knowledge base. Second, PIES determines key clinical features and actionable relationships between them which help stratify the target patient population. Third, the findings from steps 1 and 2, are validated by clinicians and all feedback is used to refine these steps and evolve the results through a continuous loop. Following these, PIES’s characterization of the target patient population is applied across clinically validated datasets for evaluation and then across multiple healthcare systems behind their firewalls to ensure scalability and privacy compliance. Results: Applied to a dataset of 100 clinically validated patients, ICD codes correctly discovers 48 lung cancer patients and misses 18 patients (i.e. who had a diagnosis of lung cancer but were miscoded). By contrast, PIES discovers 63 lung cancer patients and misses only 3 patients. Similarly, ICD codes correctly discovers 36 ovarian cancer patients and misses 16 patients in a dataset of 100 clinically validated patients. PIES correctly discovers all 52 ovarian cancer patients. Separately, in a dataset of 235 clinically validated patients, ICD codes correctly discovers 39 cachectic cancer patients and misses 122 patients. By contrast, PIES discovers 146 cachectic cancer patients and misses only 15 patients. Conclusions: Pangaea’s AI-driven product for characterizing patients discovered 48% more lung cancer patients, 62% more ovarian cancer patients and 276% more cachectic cancer patients for screening, compared to ICD codes. This includes undiagnosed and misdiagnosed patients. Pangaea’s product platform permits the evolution of knowledge for characterizing different target patient populations through its application across multiple healthcare systems, without the need to move or touch the data, thereby ensuring scalability in a privacy compliant manner.
Overall and non-lung cancer incidence in the national lung screening trial (NLST) as indicators of potential for multi-cancer screening.
Authors: Chang Ellen T. , Janes Sam M. , Hackshaw Allan , Clarke Dur Christina A. , Buist Diana SM , Hubbell Earl A. 
Published: June 2023

10633 Background: Single-cancer screening strategies address only one component of the overall population cancer burden. Even high-risk populations in single-cancer screening trials experience a considerable burden of other cancer incidence; therefore, we assessed non-lung cancer incidence in the NLST to evaluate the proportion of unscreened cancers. Methods: The NLST was a randomized controlled trial of screening for lung cancer in adults aged 55–74 years with ≥30 pack-years of smoking history, enrolled in 2002–2004 and actively followed through 2009. Incident cancers were identified via participant questionnaires, death certificates, and direct notifications, and confirmed by medical record abstraction. The present analysis includes first invasive primary cancers diagnosed after study randomization. Non-lung cancer incidence was similar between the two trial arms, which were therefore combined for analysis. Results: Among 53 229 subjects (median follow-up 6.5 years), the incidence of any first primary cancer was 1941 per 100 000 person-years, of which 1327 per 100 000 (68%) was non-lung cancer. Non-lung cancer incidence rates exceeded that for lung cancer in all 5-year age categories (especially at younger ages) and all quintiles of smoking pack-years (especially with fewer pack-years). After lung cancer, the most common cancers were other leading cancer types in the general US population, as well as other smoking-related cancers (Table). No recommended population-based screens exist for 54% of observed cancer cases (3332 of 6142, excluding lung, colon/rectum, female breast, and cervix). Conclusions: In the NLST, only 32% of first primary cancer incidence was lung; non-lung cancer comprised 68%, and most cases were cancer types with no generally recommended screening strategy. Even in a high-risk population, a single-cancer screening test misses most cancers, illustrating the value of multi-cancer screening tests that can detect a broad spectrum of cancers and, therefore, have the potential to address a currently inaccessible portion of cancer morbidity and mortality. [Table: see text]