tbuckley/cabot-search huggingface dataset:
Multimodal analysis of methylation and fragmentomic profiles in plasma cell free DNA for differentiation of benign and malignant breast tumors.
Authors: Thi Tuong Vi Van, Hanh Thi-Hue Nguyen, Thien-Chi Van Van Nguyen, Dac Ho Vo, Trung Hieu Tran, Trong Hieu Nguyen, Nhu Nhat Tan Doan, Le Anh Khoa Huynh, Xuan Vinh Nguyen, Hoa Giang, Minh-Duy Phan, Hoai Nghia Nguyen, Le Son Tran
Journal: Journal of Clinical Oncology (2024)

7 Background: Breast cancer ranks as the second leading cause of cancer-related mortality among women globally. Early detection of breast cancer is crucial for improving patient outcomes and reducing mortality rates. Liquid biopsy, which relies on circulating tumor DNA (ctDNA) shed by breast tumors into the bloodstream, presents a promising non-invasive approach for early breast cancer detection. However, accurately distinguishing between benign breast abnormalities and malignant tumors remains a significant clinical challenge, as misdiagnosis can lead to unnecessary invasive procedures. Methods: Herein, we employed a multimodal analysis approach, namely SPOT-MAS (Screen for the Presence of Tumor by DNA Methylation and Size), to profile alterations in methylation and fragment length patterns of cell-free DNA (cfDNA) from 169 breast cancer-confirmed patients and 99 patients diagnosed with benign breast lumps including cysts, fibroadenomas, and fibrocystic changes. A robust machine learning model was constructed using these signatures to differentiate between breast cancer patients and individuals with benign lesions. Results: Our genome-wide analyses identified distinct profiles of methylation changes, copy number alterations, and end motifs in cfDNA, enabling discrimination between breast cancer patients and individuals with benign conditions. Notably, we observed a significant enrichment of Thymine and Adenine at cfDNA cleavage sites in breast cancer patients. Moreover, our target sequencing analyses uncovered distinct methylation patterns in the regulatory regions of multiple genes, including hypermethylation in GPR126 or hypomethylation in TOP1 or MAFB in breast cancer cfDNA. Our multi-featured model achieved an AUC of 0.92 (95% CI: 0.88–0.97), a specificity of 97.44% and sensitivities of 57.14% and 61.70% for stage I and stage II–III patients, respectively. Furthermore, our multimodal assay effectively differentiated multiple molecular subtypes of breast tumors from benign lesions, achieving the highest sensitivity of 71.43% with Luminal A, followed by Luminal B, Triple Negative Breast Cancer (TNBC), Luminal B-HER2, and HER2 with sensitivities of 66.67%, 60%, 58.33% and 55.56%, respectively. Conclusions: Our findings demonstrate the potential of cancer-specific methylation and fragmentomic patterns in plasma cfDNA as novel biomarkers for accurately discriminating between breast cancer and benign lesions. This capability reduces the false-positive rate and helps avoid unnecessary biopsies in current clinical practice.
Research and analysis on the situation of diagnosis and treatment capabilities of breast cancer in China county.
Authors: Xiang Tan, Yi Xin, Xiaohong Yu, Huamao Zhang, Youfu Xu, Biyu Shen, Shunen Zhou, Ling Liu, Fengmei Luo, Pengkun Kang, Huarong Zhao, Zuowen Zhang
Journal: Journal of Clinical Oncology (2024)

8 Background: 1. In 2016, 306,000 breast cancer cases were newly diagnosed in China, with one-third in rural areas. Breast cancer ranked second in incidence (22.47/10 5 ) among female cancers in Sichuan Province. 2. Health resources are unequally distributed in China, especially in Sichuan Province where 43.27% reside rurally. County hospitals play a vital role in rural patients' diagnosis, treatment, and referrals. Methods: This cross-sectional observational study surveyed 124 county-level hospitals that had treated breast cancer in 183 counties in Sichuan Province from December 2023 to January 2024. Outcomes include: 1) hospital level; 2) oncology certification; 3) availability of dedicated breast department and staffing; 4) breast cancer diagnosis and treatment technology; 5) pre-treatment TNM staging rate; 6) anti-neoplastic drugs and support Accessibility of medicines. Results: Out of 124 hospitals surveyed, 6 excluded for zero breast cancer cases in 2023. The remaining 118 hospitals revealed: 1) 78.81% tertiary, 93.22% public; 2) 75.42% with special outpatient qualifications, 57.63% with concurrent special antineoplastic drug designations, 17.80% with one qualification; 3) 57.63% with dedicated breast units, but only 16.1% with specialized breast cancer staff; 4) 31.36% with full breast imaging modalities, 78.23% lacking mammography; PET-CT and bone scan availability: 5.93% and 9.32%; 5) 71.19% with independent pathology, but only 30.65% providing comprehensive services; 6) Surgeries for breast cancer: 86.44% (44.07% breast conservation), radiation therapy availability: 39.83%; 7) AJCC TNM staging rate: 77.12%; 8) Antineoplastic accessibility: conventional chemotherapy (93.22%), anti-HER2 therapy (28.81%), endocrine therapy (47.46%), CDK4/6 inhibitors (26.27%, with 41.53% having only one); 9) Analgesics: 87.90% (morphine 94.92%, tramadol 88.98%, fentanyl patches 34.75%, oxycodone 46.61%); antiemetics (5-HT3 antagonists 69.49%, NK1 antagonists 72.88%, olanzapine 48.31%, metoclopramide 64.41%); medications for hematologic toxicity: 51.61%. Conclusions: Shortages exist in specialized breast care units and trained personnel among county hospitals in Sichuan, China. Special outpatient qualifications and antineoplastic prescription credentials concentrated mainly at tertiary centers. Enhancing imaging and histopathology capacities for breast cancer diagnosis is an urgent need. While conventional chemotherapies demonstrate good accessibility, anti-HER2 targeted therapies, endocrine therapies, and CDK4/6 inhibitors covered by national insurance have limited availability. Enhanced provision of new antiemetics and analgesics is needed. [Table: see text]
Changes in the treatment landscape of metastatic hormone-sensitive prostate cancer: A multicenter study.
Authors: Fumihiko Urabe, Takahiro Kimura
Journal: Journal of Clinical Oncology (2024)

118 Background: A multicenter database was utilized to examine the current treatment landscape and clinical outcomes among patients with metastatic hormone-sensitive prostate cancer (mHSPC) following approval of upfront androgen receptor signaling inhibitors (ARSIs). Methods: We retrospectively analyzed patients with mHSPC who commenced treatment between February 2018 and June 2023. The Kaplan–Meier method was used to assess oncological outcomes, including time to castration-resistant prostate cancer (CRPC), progression-free survival 2 (PFS2, duration from initial treatment to tumor progression during second-line treatment), cancer-specific survival (CSS), and overall survival (OS). Cox regression analyses were performed to determine the impact of treatment choices on oncological outcomes. In addition, the incidence rate of adverse events was assessed. Results: In total, 829 patients were analyzed; 42.5% received ARSIs with androgen deprivation therapy (ADT), 44.0% received combined androgen blockade (CAB), and 13.5% received ADT alone. Analysis of annual treatment choice trends revealed an increasing preference for ARSIs with ADT. Kaplan–Meier curves and multivariate Cox regression analyses indicated higher rates of CRPC and shorter PFS2 in patients treated with CAB versus ARSIs with ADT. By contrast, CSS and OS were not significantly different between the ARSI with ADT group and the CAB group. Grade 3–4 adverse events occurred in 1.9% of patients receiving CAB and 6.0% of those receiving ARSIs with ADT. Conclusions: For patients with mHSPC, initial treatment with ARSIs in combination with ADT resulted in a longer time to CRPC and longer PFS2 compared to CAB. Although CAB and ADT alone were associated with fewer adverse events, ARSIs with ADT should be considered a first-line treatment option given its superior oncological outcomes.
Nationwide analysis of patients with ovarian cancer: Racial status and risk of metastasis.
Authors: Thanathip Suenghataiphorn, Narathorn Kulthamrongsri, Tuntanut Lohawatcharagul, Chalermkiat Kansuttiviwat, Sakditad Saowapa
Journal: Journal of Clinical Oncology (2024)

124 Background: Literature review has found profound disparities in clinical outcomes, for patient with ovarian cancer. Metastasis is the primary cause of cancer morbidity and mortality. However, data on the metastasis risks on hospitalized individuals with ovarian cancer is still limited. Therefore, we aim to assess the association between metastatic ovarian cancer and racial differences using large database analysis. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to explore patients who have ovarian cancer as the primary diagnosis. Additionally, we identified evidence of metastasis, as recorded by ICD-10-CM. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was racial differences in organ metastasis and secondary outcomes included mortality and length of stay. Statistical significance was established at p-value of 0.05. Results: We identified 19,789 patients with primary diagnosis of ovarian cancer at discharge. The mean age was 61.6 years. Caucasians accounted for 68.3%, with Hispanics at 11.1 % and African Americans at 9.7%. We found that 7% of the patients had liver metastasis. In a multivariate analysis adjusting for patient, COVID-19, chemotherapy usage and hospital factors, African Americans and Hispanics had higher risk of liver metastasis (aOR 1.95; 95%CI (1.32, 2.88), p = 0.001) (aOR 1.78; 95%CI (1.19, 2.66), p = 0.004). We also observed reduced length of stay for Asian Americans (b = -0.74; 95%CI (-1.31, -0.17), p = 0.011). We observed an increase in risk of metastasis and mortality but non-statistically significant in some parameters and races, as shown in table provided. Conclusions: In conclusion, our study revealed that racial difference is associated with higher risk of metastasis, as well as other outcomes. More studies following patients over time are needed to determine if race directly affects how ovarian cancer spreads and other clinical outcomes. [Table: see text]
In-hospital outcome of central nervous system malignancy with COVID-19 infection: Analysis from National Inpatient Sample (NIS).
Authors: Thanathip Suenghataiphorn, Phuuwadith Wattanachayakul, Thitiphan Srikulmontri, Sakditad Saowapa, Kochakorn Buasri, Narathorn Kulthamrongsri
Journal: Journal of Clinical Oncology (2024)

29 Background: Previous research highlights central nervous system (CNS) malignancy as significant contributors to disability-adjusted life-years. However, there's a lack of information on the impact of COVID-19 infection in hospitalized CNS malignancy patients. Methods: Using the 2020 U.S. National Inpatient Sample (NIS), we investigated the impact of COVID-19 infection affected patients primarily hospitalized for CNS malignancy. We calculated adjusted odds ratios (aORs) for specific outcomes using multivariable logistic and linear regression analyses. The primary outcome was inpatient mortality, with secondary outcomes including system-based complications. Results: We identified 37,385 patients diagnosed with CNS malignancy, averaging 53.6 years old, with 57.76% being female. Among them, 0.84% (315/37,385) were also diagnosed with COVID-19. After adjusting for patient and hospital factors, COVID-19 infection was linked to higher in-hospital mortality (aOR 4.12, 95% CI: 1.55, 10.89, p = 0.004), longer stays (Beta-coefficient 6.06, 95% CI: 2.97, 9.14, p &lt; 0.001), increased total hospital costs (Beta-coefficient 11,855, 95% CI: 1,410, 22,301, p = 0.026), elevated risks of shock (aOR 3.96, 95% CI 1.03, 15.10, p = 0.018), acute respiratory failure (aOR 4.33, 95% CI: 1.83, 10.22, p = 0.001), and sepsis (aOR 3.96, 95% CI: 1.03, 15.10, p = 0.044). Conclusions: Our study reveals that COVID-19 infection is associated with higher in-hospital mortality and multiple adverse outcomes in patients hospitalized for CNS malignancy. Further longitudinal studies are necessary to thoroughly investigate the causality of these clinical outcomes in this population.
Efficacy of a mountain craft training in improving resilience and psychological well-being and reducing fatigue in childhood cancer survivors.
Authors: Joyce Oi Kwan Chung
Journal: Journal of Clinical Oncology (2024)

TPS167 Background: This pilot study aims to determine the feasibility, acceptability, and preliminary efficacy of mountain craft training in improving resilience and quality of life and reducing fatigue and depressive symptoms in childhood cancer survivors (CCS). Methods: A randomised controlled trial. A sample of 40 CCS, aged 10 to 16, will be invited to participate in this study. Resilience scale, Center for epidemiologic studies depression scale; Paediatric Quality of Life Inventory; and Fatigue Scale – Child will be used to assess resilience, depressive symptoms, health-related quality of life and levels of fatigue, respectively. Participants in the intervention group will receive two 30-45 mins lectures on resilience, physical exercise, knowledge and skills in mountain craft; and a 4-day hiking programme on weekends over a 3-month period. Participants in the control group will participate in 4 day of leisure activities on weekends over a 3-month period. The main outcome measure: The participants’ level of resilience at 6-month post intervention The Statistical Package for Social Sciences (SPSS) software (version 26.0) will be used to analyse the quantitative data. Pearson chi-square test or Fisher’s exact test for categorical variables, and the independent sample t-test for continuous variables. The Generalised Estimating Equation (GEE) will be employed to determine the changes between the intervention and placebo control groups, the within-group (time) effects, and the interaction effects.
Descriptive and content analysis of breast cancer vlogs on YouTube.
Authors: Ari N. Meguerditchian, Elly Htite, Yitzchok Ahisar, Victoria Hayman, Carrie A. Rentschler, Nina Morena
Journal: Journal of Clinical Oncology (2024)

18 Background: Vlogs, or “video blogs,” are personally-created experiential videos based on wide-ranging topics, usually posted to YouTube. Many women with breast cancer (BC) document their cancer experiences in YouTube vlogs. These may have the potential to serve as peer-to-peer support and provide community. This study provides a descriptive and content analysis of vlogs by women with BC. Methods: YouTube was searched in incognito mode in 11/2023 using the search terms “breast cancer vlog.” A maximum of 10 videos/creator were included based on viewership and date created. Video characteristics collected included: title, length, number of views, likes, comments, and playlist inclusion. Videos were assessed for sponsorship, presence of explanation and discussion on BC, type of content, and themes. Creator characteristics included age, location, and engagement approaches. Descriptive and content analysis were performed to assess and analyze video content and potential areas where peer-to-peer support may be provided. Results: 90 vlogs by 13 creators were included, all originating from personal accounts. Mean video length, number of views, and number of comments were 21.4 minutes (SD 9.1), 266,780 (SD 534,465), and 1485 (SD 3422), respectively. 38.9% included hashtags. 12.2% included paid sponsorships. Most common filming location was at home (96.7%), followed by the hospital (31.1%), or in the car (21.1%). Home vlogs were most often set in the living room (44.3%), bedroom (33.0%), or kitchen (20.6%). 56.7% included visuals of treatment as well as physical findings. Creators addressed motivation for vlogging in 48.9%; the two most common reasons were wanting to build a community and helping others in a similar situation. In 46.7%, creators explicitly expressed emotion. Most common themes were treatment (85.6%), mental health (81.1%), side effects (72.2%), appearance (63.3%), and family relationships (36.7%). Subthemes included young age, finances, and the importance of online community support. Patient-directed advice was offered in 60.0%, mostly on treatment-related issues. In 56.7%, creators provided explicit treatment definitions. Chemotherapy was discussed in 70.0%; surgery in 57.8%, primarily mastectomy; radiation in 30.0%; general side effects in 71.1%. 24.4% were about a new diagnosis. When mentioned (44.4%), most common creator location was the USA. When mentioned (30.0%), most common age demographic was 20-29 years old. Conclusions: Vlogs by women with BC receive significant levels of engagement. The dedication to building community demonstrated by vlog creators, and the personal nature of their storytelling, advice, and suggestions, may make these vlogs a potential resource for peer-to-peer support.
Safety analysis by treatment periods from EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization with durvalumab with/without bevacizumab in participants with embolization-eligible unresectable hepatocellular carcinoma.
Authors: Masatoshi Kudo, Stephen Lam Chan, Bruno Sangro, Joseph P. Erinjeri, Shukui Qin, Zhenggang Ren, Yasuaki Arai, Valeriy Vladimirovich Breder, Shi-Ming Lin, Jean-Marie Peron, Tien Quang Nguyen, Lunan Yan, Chang-Fang Chiu, Florinda A. Santos, Anil Veluvolu, Satheesh Chiradoni Thungappa, Claire Morgan, Kerry Parsons, Ioannis Xynos, Riccardo Lencioni
Journal: Journal of Clinical Oncology (2024)

65 Background: The global Phase 3 EMERALD-1 study (NCT03778957) primary endpoint was met: durvalumab (D) + bevacizumab (B) + transarterial chemoembolization (TACE) significantly improved progression-free survival vs placebos (pbos) + TACE (median 15.0 vs 8.2 mo; HR, 0.77; 95% CI, 0.61–0.98; p=0.032 [threshold 0.0435]) in participants (pts) with embolization-eligible unresectable hepatocellular carcinoma (uHCC) with a manageable safety profile. This post hoc, exploratory analysis assessed safety in the study’s two treatment (tx) periods (pds): D-TACE (D-T) and D-B. Methods: Pts were randomized 1:1:1 to D+TACE, D+B+TACE, or pbos+TACE. In the D-T pd, pts received 1–4 TACE (cTACE or DEB-TACE [investigator choice]) plus D (1500 mg Q4W) or pbo for D. In the D-B pd, post-last TACE, pts received D (1120 mg Q3W) plus pbo for B, D (1120 mg Q3W) plus B (15 mg/kg Q3W), or pbos for D and B. Adverse events (AEs), start/end date, maximum/change in CTCAE grade, and causality were assessed in the D-T and D-B pds in pts who received any study tx in the arm to which they were randomized, until end of follow-up. Results: The Table shows duration of exposure (DoE). In the D+TACE, D+B+TACE, and pbos+TACE arms, AEs were reported by 144 (74.6%), 139 (72.0%), and 148 (74.0%) pts in the D-T pd and 133 (68.9%), 147 (76.2%), and 132 (66.0%) pts in the D-B pd; were possibly related (pos rel) to study tx in 59 (30.6%), 56 (29.0%), and 41 (20.5%) pts in the D-T pd and 76 (39.4%), 114 (59.1%), and 69 (34.5%) pts in the D-B pd; and were provoked by TACE in 72 (37.3%), 90 (46.6%), and 85 (42.5%) pts in the D-T pd and 16 (8.3%), 18 (9.3%), and 21 (10.5%) pts in the D-B pd, respectively. Conclusions: D+B+TACE had a manageable safety profile across the D-T and D-B pds, consistent with the individual agents and underlying disease. These data further support D+B+TACE as a new potential standard of care in embolization-eligible uHCC. Clinical trial information: NCT03778957 . [Table: see text]
Feasibility of pretreatment FDG PET radiomics in predicting circumferential margin involvement for esophageal cancer after neoadjuvant concurrent chemoradiotherapy.
Authors: Wei-Chih Shen, Ying-Hsiang Chou, Meng-Wei Chung, Guo-Zhi Wang, Jang-Ming Lee, Yi-Han Liao
Journal: Journal of Clinical Oncology (2024)

203 Background: Involvement of circumferential resection margin (CRM) proves to be a valuable factor in predicting prognosis for patients with esophageal cancer. This study aimed to explore the feasibility of using pretreatment 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in predicting CRM involvement for patient received neoadjuvant concurrent chemoradiotherapy (CCRT). Methods: We retrospectively enrolled patients with esophageal cancer who received neoadjuvant CCRT followed by radical surgery between October 2013 and July 2023. All patients received FDG PET/CT examinations before CCRT. The maximum standardized uptake value (SUV max ) within a tumor was identified, and the metabolic tumor volume (MTV) was calculated by using a fixed SUV threshold method (50 % of SUV max ). Descriptive features and five groups of radiomic features (Gray Level Co-occurrence Matrix [GLCM], Gray Level Dependence Matrix [GLDM], Gray Level Run Length Matrix [GLRLM], Gray Level Size Zone Matrix [GLSZM], and Neighboring Gray Tone Difference Matrix [NGTDM]) were further calculated to describe the heterogeneity of the FDG uptakes within MTV. The CRM involvement status was defined by the Royal College of Pathologists (RCP). Tumor presence at or within 1 mm of the cut margin was considered CRM positive. Finally, we used the area under the receiver operating characteristic curve (AUC) to evaluate the predictive performance of radiomic features for CRM. The significance level was set to 0.05. Results: A total of 71 cases of esophageal tumors, encompassing data from 70 patients were included. Of the 70 patients, 94% were male with a mean age 58 years across the entire cohort. Sixteen tumors were proved as CRM positive (16/71, 22.5%). Finally, 2 descriptive features and 10 radiomic features were selected that can effectively predict CRM status. These ten radiomic features exhibit robust predictive power for CRM status, demonstrating significance across various discretization bin number. The best performing feature is Skewness (AUC=0.716, p-value&lt;0.0001). Conclusions: This preliminary result revealed that CRM involvement for esophageal cancer tumors could be predicted by using radiomic features. Future studies are warranted for clinical application. [Table: see text]