tbuckley/cabot-search huggingface dataset:
Clinical and molecular characteristics and targeted therapy of pediatric non-infantile fibrosarcoma NTRK rearrangement–related tumors.
Authors: Junting Huang, Mengjia Song, Suying Lu, Yu Zhang, Shan Wang, Yanpeng Wu, Ruiqing Cai, Juan Wang, Jia Zhu, Feifei Sun, Zijun Zhen, Yizhuo Zhang
Journal: Journal of Clinical Oncology (2024)

10048 Background: Neurotrophic tyrosine receptor kinase (NTRK) rearrangement is rare in tumors and relevant to targeted therapy. Pediatric NTRK rearrangement-related tumors have distinct clinical and molecular features compared to adults, and previous studies on pediatric NTRK rearrangement-related tumors has focused on infantile fibrosarcoma (IFS), the most common subtype. However, the clinical behaviors and molecular profiles of other subtypes of pediatric NTRK rearrangement-related tumors are largely unknown. Methods: In this study, we evaluated the molecular features, treatment response, and prognosis of 28 pediatric patients with non-IFS NTRK rearrangement-related tumors. Next-generation sequencing was performed in 21 patients to identify the NTRK fusion types and their co-occurring alterations, and pathway enrichment analysis was performed to explore the potential mechanisms involving NTRK rearrangement and resistance to tyrosine receptor kinase (TRK) inhibitors. Results: The NTRK fusion partners were diverse and tumor-specific. Several novel NTRK fusions were identified, including SNIP1-NTRK1, AGAP1-NTRK2, CRCT1-NTRK1, ZBTB7B-NTRK1, and SLC6A15-NTRK3. RTK-RAS, NOTCH, TP53, and WNT pathways were top 4 significantly enriched in tested samples. Twelve of 17 patients (70.6%) received TRK inhibitors as salvage treatment achieved complete or partial response. Patients who did not develop DDR, NOTCH, or TP53 pathway-related gene mutations had a high objective response rate of 82%, 82%, and 83%, respectively. Conclusions: Our findings may have important implications for the diagnosis and treatment of non-IFS NTRK fusion-positive tumors in pediatric patients. We also provide potential therapeutic targets for tumors resistant to TRK inhibitors. Clinical trials with TRK inhibitors, either alone or in combination, are required to establish the optimal treatment regimen and sequence in large-cohort pediatric patients with non-IFS NTRK rearrangement-related tumors. Clinical trial information: NCT05076071 .
Bismuth Chelate‐Mediated Digital Subtraction Angiography
Authors: Jiaojiao Wang, Dianxun Fu, Cong Tang, Gang Shu, Xuejun Zhang, Xuening Zhang, Jinbin Pan, Shao‐Kai Sun
Journal: Advanced Healthcare Materials (2024)

Digital subtraction angiography (DSA) is considered the "gold standard" for the diagnosis of vascular diseases. However, the contrast agents used in DSA are limited to iodine (I)-based small molecules, which are unsuitable for patients with contraindications. Here, iodine-free DSA utilizing a bismuth (Bi) chelate, Bi-DTPA Dimeglumine, is proposed for vascular visualization for the first time. Bi-DTPA Dimeglumine possesses a simple synthesis process without the need for purification, large-scale production ability (over 200 g in the lab), superior X-ray imaging capability, renal clearance capacity, and good biocompatibility. Bi-DTPA-enhanced DSA can clearly display the arteries of the rabbit's head and lower limbs, with a minimum vascular resolution of 0.5 mm. The displayed integrity of terminal vessels by Bi-DTPA-enhanced DSA is superior to that of iopromide-enhanced DSA. In a rabbit model of thrombotic disease, Bi-DTPA Dimeglumine-enhanced DSA enables the detection of embolism and subsequent reevaluation of vascular conditions after recanalization therapy. This proposed iodine-free DSA provides a promising and universal approach for diagnosing vascular diseases.
Barriers to implementing clinical cancer genetics in sub-Saharan Africa: Perspectives of participants of a virtual cancer genetics course.
Authors: Temidayo Fadelu, Achille Van Christ Manirakiza, Annette Uwineza, Francois Uwinkindi, Diane R. Koeller, Timothy Rebbeck
Journal: Journal of Clinical Oncology (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.
Breast cancer polygenic risk score and patient survival outcomes in the Pathways study.
Authors: Arya Mariam Roy, Nur Zeinomar, Haiyang Sheng, Janise M. Roh, Cecile Laurent, Isaac J. Ergas, Jennifer Delmerico, Qianqian Zhu, Marilyn L. Kwan, Lawrence H. Kushi, Christine B. Ambrosone, Song Yao
Journal: Journal of Clinical Oncology (2024)

10502 Background: Many common, low-penetrance variants have been identified for breast cancer risk through genome-wide association studies, leading to the development of polygenic scores (PGS) to aggregate the effects of individual variants for risk prediction. Much less is known about genetic determinants of breast cancer-related outcomes. We hypothesized that breast cancer patients with high breast cancer PGS are at risk of a second breast-related adverse event, such as recurrence, contralateral breast cancer, or death. Methods: The Pathways Study is a prospective cohort study of breast cancer survivors enrolled shortly after diagnosis in 2006-2013 at Kaiser Permanente Northern California, with ongoing follow-up. Genome-wide genotype data were available from 3,995 patients for calculation of 4 PGS, including PGS 313 , PGS 4k , PGS 5k , and PGS 6m . Scores were categorized into tertiles to investigate their associations with 7 survival outcomes including recurrence, contralateral second primary breast cancer, other second primary cancer, and death. Hazard ratios (HR) and 95% confidence intervals (CI) were derived from multivariable Cox proportional hazards regression models. Results: The median age at diagnosis was 60 (23.6-94.8) years, and most (68%) self-identified as White. Many women had estrogen receptor (ER)+ (83.4%), stage I and II tumors (89%), with 13.3% HER2+ tumors. The majority (60%) received lumpectomy and some type of adjuvant therapy (44.3% radiotherapy, 47.0% chemotherapy, and 74.6% received hormonal therapy). By December 31, 2021, the median follow-up time was 10.5 (0.2-14.2) years, with 504 recurrences, 419 total second primary cancers, 146 contralateral second primary breast cancers, 237 non-breast second primary cancers, and 762 deaths (352 breast cancer-specific deaths) observed. In Table 1, patients with medium (T2) and high (T3) PGS 313 had higher risk of recurrence, but not contralateral breast cancer or other second primary cancer. They also had higher risk of all-cause death, breast cancer-specific death, total breast cancer event, and invasive disease. The other 3 PGS were not associated with survival outcomes examined. Conclusions: Our study reveals that breast cancer patients with higher PGS 313 had higher risk of recurrence, total breast cancer and invasive breast cancer events, and death. These findings highlight a potential role of breast cancer PGS for prognosis, warranting further exploration. [Table: see text]
Budget impact model of LungFlag, a predictive risk model for lung cancer screening.
Authors: Michael K. Gould, Eran Netanel Choman, Nicolò Olghi, Milan Obradovic, Sarika Ogale, Carolina Heuser Sanmartin
Journal: Journal of Clinical Oncology (2024)

10534 Background: Lung cancer screening (LCS) programs using low-dose computed tomography (LDCT) for early detection reduce mortality and have been widely recommended. LungFlag is a machine-learning risk prediction model that uses patient-level data to identify individuals at high risk of developing non-small cell lung cancer (NSCLC), prompting their physician to recommend screening with LDCT. Methods: A budget impact model was developed to estimate the costs associated with adoption of LungFlag as an adjunct to existing US Preventive Services Task Force (USPSTF) screening guidelines for a hypothetical US commercial health plan population of 1 million beneficiaries. The model calculates the total expected annual costs of screening for NSCLC with LDCT in scenarios with and without LungFlag, including healthcare resource utilization for detecting NSCLC and treatment of patients diagnosed with NSCLC. Incremental costs were evaluated over a 5-year period. Results: Among 36,803 USPSTF-eligible persons, we assumed that 4600 (12.5%) had already initiated LCS, leaving 32,203 persons who were candidates for pre-screening with LungFlag. The model estimated that 17 additional NSCLC diagnoses per year would be detected by screening when using LungFlag, with most in stage 1. Over 5 years, LungFlag was estimated to result in 33 fewer patients with stage 3 or stage 4 NSCLC at diagnosis and 22 fewer NSCLC-related deaths. Use of LungFlag increased annual costs during the first 2 years and provided cost savings from Year 4 onwards (Table). Cost savings from LungFlag were attributable to reductions in the costs of advanced NSCLC treatment. Conclusions: In a population of 1 million commercial health plan beneficiaries, the adoption of LungFlag as an adjunct to existing screening guidelines for USPSTF-eligible patients was estimated to prevent 22 additional NSCLC-related deaths, with a cost savings of $2.87 million over 5 years from a US commercial payer perspective. [Table: see text]
Radiation dose escalation and local control for intermediate-risk rhabdomyosarcoma on ARST1431: A report from the Children’s Oncology Group
Authors: Christopher Jackson, Wei Xue, ABHA A. GUPTA, Amira Qumseya, Roshni Dasgupta, Christine E. Hill-Kayser, Aaron Spalding, David A. Rodeberg, Douglas James Harrison, Rajkumar Venkatramani, Suzanne L. Wolden
Journal: Journal of Clinical Oncology (2024)

10007 Background: The objective of this study was to evaluate local failure (LF) rates for patients with intermediate-risk rhabdomyosarcoma (IR-RMS) treated on the Children’s Oncology Group (COG) ARST1431 clinical trial. To improve local control, the radiation therapy (RT) dose was increased to 59.4 Gy for patients with tumors &gt; 5cm at diagnosis and residual gross disease at the time of RT. Methods: The297 patients randomized on ARST1431 were included. LF was defined as progression or relapse at the primary tumor site. Gray’s test was used to compare the cumulative incidence of LF across variables. Results: There was a trend for lower 3-year LF in group III patients with fusion-positive disease (11.1%, 95% confidence interval (CI) 4.5%-21.1%) compared to patients with fusion-negative disease (21.8%, 95% CI 15.8%-28.4%), p = 0.09.There was no difference in the 3-year LF rate for patients who underwent proton RT (16.3%, 95% CI 9.6%-24.7%) compared to photon RT (16.2%, 95% CI 10.2%-23.6%;), p = 0.8. The 3-year LF rate for all patients with tumors &gt; 5cm at diagnosis (24.9%, 95% CI 18.6%-31.7%) was significantly higher than that of patients with tumors ≤5cm at diagnosis (9.9%, 95% CI 5.2%-16.4%), p &lt; 0.01. Of 81 patients with tumors &gt; 5cm and residual gross disease after induction chemotherapy who went on to receive RT, 62 (76.5%) received the protocol-specified boost to 59.4 Gy. Patients who received the boost had a 3-year LF rate of 32.1% (95% CI 20.1%-44%), while patients who did not undergo an RT boost had a 3-year LF rate of 16.1% (95% CI 3.8%-36.2%), p = 0.3. For patients with group III, non-parameningeal disease, those who underwent delayed primary excision (DPE) had a significantly lower LF rate compared to those who did not undergo DPE (3-year rate of 5.6% (95% CI 1.4%-14.0%) vs. 22.0% (95% CI 14.5-30.7%), p &lt; 0.01). Conclusions: On ARST1431, larger tumors ( &gt; 5cm at diagnosis) were associated with increased risk of LF. Dose escalation to 59.4 Gy did not improve local control for patients with tumors &gt; 5cm at diagnosis with residual gross disease at the time of RT. For a select group of non-parameningeal, group III patients who underwent DPE followed by RT, local control was improved. Clinical trial information: NCT02567435 .
Cervical cancer screening in 48000 females over two decades: Feasibility and success of community-based screening in Kerala, India.
Authors: D. Krishnanadha Pai, B.V. Bhat, Harsha Gangadharan, Pankaj Kumar Panda, Ravindran V C, Lopamudra Das Roy, Sujith Kumar Mullapally
Journal: Journal of Clinical Oncology (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.
Associations between metabolic syndrome-related diseases and colorectal cancer risk: A propensity score-matched analysis using the NIH All of Us research program.
Authors: Yong Eun, Rahman Adesoji Olusoji, Noah Osei, Ibrahim Omore, Meena Ahluwalia
Journal: Journal of Clinical Oncology (2024)

10515 Background: The risk of colorectal cancer (CRC) is known to increase in patients with metabolic disorders such as hypertension (HTN), hyperlipidemia (HLD), type 2 diabetes (T2DM), and metabolic associated fatty liver disease (MASLD). Both metabolic disorders and CRC share similar demographic, socioeconomic, geographic, and environmental risk factors. This study aims to examine the associations between metabolic syndrome-related diseases and CRC incidence, controlling for confounding risk factors. Methods: This was a propensity score matched case-control study using NIH All of UsResearch Program, Registered Tier version 7. CRC diagnoses was defined as having two or more diagnosis codes in EHR. We matched CRC patients to participants without CRC diagnosis with 1:2 ratio, aligning age, gender, race/ethnicity, income, education, region, and cigarette exposure. Income level per year ( &lt; $25K, $25-100K, &gt; $100K), education level (grade 12 or less, some college, college graduate), cigarettes exposure ( &gt; 100 cigs per lifetime), region (Northeast, Midwest, South, West) were assessed using the survey. Height and weight measurement collected at the time of enrollment was used to calculate BMI and define obese (BMI ≥ 30 kg/m 2 ) and underweight (BMI &lt; 18.5 kg/m 2 ) status. We compared the average BMI between two groups, and calculated the odds ratios for obesity, underweight status, HTN, HLD, T2DM, and MASLD to assess the likelihood of these conditions being associated with colon cancer. Results: Between the control (n = 3,528) and CRC groups (n = 1,764), there was no significant differences in matched factors. The CRC group had a similar obesity prevalence and a lower mean BMI (28.8, SD 6.9) compared to the control group (29.3, SD 6.9, p = 0.017). Underweight status was linked to a 76% increase in CRC odds (OR 1.76, CI 1.21-2.56, p = 0.003), T2DM to a 26% increase (OR 1.26, CI 1.06-1.49, p = 0.008), HTN to a 58% increase (OR 1.58, CI 1.41-1.78, p &lt; 0.001), HLD to a 32% increase (OR 1.32, CI 1.18-1.49, p &lt; 0.001), and MASLD to over a two-fold increase (OR 2.16, CI 1.78-2.61 p &lt; 0.001). Conclusions: Our study reinforces the significant link between metabolic dysregulation and CRC risk. The higher prevalence of metabolic disorders in the CRC group, despite a lower obesity prevalence and average BMI, suggests that other factors, potentially treatment effects, might contribute to these findings. Further research is warranted to elucidate the causal pathways linking metabolic disorders to the pathogenesis of CRC. [Table: see text]
Utility of colposcopy for the screening and management of cervical cancer in Africa: A cross-sectional analysis of providers’ training and practices.
Authors: Joel Fokom Domgue, Issimouha Dille, Freddy Houéhanou Rodrigue Gnangnon, Sharon Kapambwe, Céline Bouchard, Nomonde Mbatani, Elodie Gauroy, Nathalie Ambounda Ledaga, Robert K Yu, Fatoumata Matokoma Sidibe, Joseph Kamgno, Pierre-Marie Tebeu, Gregory Halle-Ekane, Mohenou Isidore Diomande, Jean-Marie Dangou, Fabrice Lecuru, Isaac Folorunso Adewole, Marie-Elaine Plante, Partha Basu, Sanjay Shete
Journal: Journal of Clinical Oncology (2024)

10555 Background: Cervical cancer is a public health issue in Africa with devastating socioeconomic consequences due to the lack of organized screening programs. The success of screening programs depends on the appropriate investigation and management of women who test positive for screening. Colposcopic assessment following positive screening results is a critical issue in Africa. This study aimed to assess the utilization of colposcopy by providers in the region. Methods: A cross-sectional study was conducted in 2021-2022 among healthcare providers involved in cervical cancer prevention activities in Africa. They were invited to report prior colposcopy training, whether they performed colposcopy and the indications of colposcopy in their practice. Results: Of the 130 providers from 23 African countries who responded to the survey (mean age [SD]: 39.0 years [9.4]), half were female (65 [50.0%]), and 90.7% were working in urban areas. Overall, only 12.6% of respondents indicated having received prior training on colposcopy, and 11.7% reported that they were performing colposcopy in their current practice. Among the providers who reported performing colposcopy in their practice, colposcopy was indicated for routine visual screening in 21.2% of clinicians, to visualize the transformation zone in 15.2% of respondents, to assess vascularization of cervical mucosa in 33.3% of respondents, and to determine treatment modality in 12.1% of respondents. Conclusions: Providers’ training and utilization of colposcopy for cervical cancer screening remain suboptimal in Africa. To address this situation in the region, further training is needed to improve providers' knowledge and engagement. With the development of lower-cost and portable colposcopes, efforts to equip cervical cancer prevention programs and facilities with colposcopy should be enhanced to ensure that women can be screened and managed appropriately.