tbuckley/cabot-search huggingface dataset:
Effectiveness of mobile computerized tomographic (CT) lung scanning unit for early diagnosis of lung cancer in under-served populations.
Authors: Derek Raghavan, Darcy L Doege, Mellisa S Wheeler, John D Doty, James Oliver, Edward S. Kim, Kathryn Finch Mileham, Daniel R. Carrizosa
Journal: Journal of Clinical Oncology (2019)

6567 Background: The National Lung Screening Trial (NLST) demonstrated that screening high-risk patients with low-dose CT (LDCT) of the chest reduces lung cancer mortality compared to screening with chest x-ray. Uninsured and Medicaid patients lack access to this hospital-based screening test due to geographic isolation/socio-economic factors. We hypothesized that a mobile screening unit would improve access and confer benefits demonstrated by the NLST to this under-served group, which is most at risk of lung cancer deaths. Methods: In collaboration with Samsung Inc, we inserted a BodyTom portable 32 slide low-dose CT scanner into a 35-foot coach, reinforced to avoid equipment damage, to function as a mobile lung scanning unit. The unit includes a waiting area, high speed wireless internet connection for rapid image transfer, and electronic tablets to deliver smoking cessation and health education programs and shared decision-making video aids. It has been certified as a lung cancer screening Center of Excellence by Lung Cancer Alliance. We employed the LUNG RADS approach to lesion classification, yielding high sensitivity and specificity in assessment. All films were reviewed by a central panel of oncologists, pulmonologists and radiologists. The protocol was approved by Chesapeake IRB, which oversees all LCI cancer trials. Interim analysis at this time was approved by the Oversight Committee. Results: We screened 470 under-served smokers between 4/2017-1/2019; M:F 1.1:1, mean age 61 years (range 55-64), with average pack year history of 45.7 (30-150) (25% African-American; 3% Hispanic; 65% rural; 100% uninsured, under-insured or Medicaid - NC Medicaid does not cover lung cancer screening). Patients over the age of 64 years were excluded as they are covered by Medicare for lung cancer screening. We found at initial screen 35 subjects with LUNG RADS 4 lesions, 49 subjects with LUNG RADS 3 lesions, 10 lung cancers (2.1%), including 4 at stage I-II. 4 non-lung cancers were identified and treated. Other incidental non-oncologic findings are the subject of another presentation. Conclusions: In this small sample using the first mobile low dose CT lung screening unit in the United States, the initial cancer detection rate is comparable to that reported in the NLST but with marked improvement of screening rates in underserved groups and with better anticipated outcomes at lower cost than if they had first presented with metastatic disease.
The association between female hormonal supplementation and molecular types in colorectal cancer.
Authors: Seung Won Chung, Michael J. Overman, Van K. Morris, David R. Fogelman, Bryan K. Kee, Arvind Dasari, Kanwal Pratap Singh Raghav, Imad Shureiqi, Zhi-Qin Jiang, Patricia A. Jensen-Loewe, Robert A. Wolff, Cathy Eng, David Menter, Scott Kopetz, Jennifer S. Davis
Journal: Journal of Clinical Oncology (2019)

e15133 Background: In the US, colorectal cancer is the third most common malignancy in women. Postmenopausal hormone use has been associated with decrease in incidence of colorectal cancer however few studies have evaluated the relationship between hormone use and molecular profiles of advanced colorectal cancer. The aim of this study is to evaluate correlations between female hormonal supplementation use and colorectal cancer molecular, clinical, and pathologic features. Methods: We conducted a retrospective case-case study of female patients with metastatic or unresectable, locally advanced colorectal cancer on the Assessment of Targeted Therapies Against Colorectal Cancer (ATTACC) protocol from 2010 to 2017. Post-menopausal hormone use was self-reported in an environmental survey as part of the ATTACC protocol. Molecular, clinical, and pathologic features were obtained through medical record review. Results: Among 258 female patients, 163 (63%) patients reported ever use of female hormonal supplementation. Ever use was significantly associated with BRAF V600E mutant tumors (OR 2.63, p-value 0.04). There was no association with KRAS, NRAS, PIK3CA mutations, microsatellite instability, or CpG island methylation. The mean age at diagnosis of ever users was 54.4 and mean of no supplement was 56.5 (p-value 0.07), indicating no age difference between ever and never users. Conclusions: Despite the overall protective effects of postmenopausal hormone use on colorectal cancer incidence, among those who develop colorectal cancer, our data suggest an association between female hormonal supplementation and BRAF mutation. Further studies are needed to evaluate this relationship in additional cohorts, interrogate the biological basis, and identify whether there is an association with survival of patients with metastatic or locally advanced colorectal cancer with estrogen or progestin supplement use.
AB1376-HPR ROLE OF NURSE-LED TELEPHONE FOLLOW UP TO ENHANCE AND SUBSEQUENTLY MAINTAIN HIGH LEVEL OF ADHERENCE TO OSTEOPOROSIS PROPHYLAXIS MEDICATIONS: A PROSPECTIVE COHORT STUDY OF PATIENTSWITH POLYMYALGIA RHEUMATICA AND GIANT CELL ARTERITIS
Authors: Pia Toftegaard, Amir Emamifar, Alexandra Brink Walling, Susanne Højmark Jakobsen, Peter Thye-Rønn
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Poor adherence to the osteoporosis prophylaxis medications has been reported before, which may result in treatment failure.<sup>1</sup> However findings of previous studies are controversial.<sup>1,2</sup> <h3>Objectives</h3> To investigate the role of nurse-led telephone follow-up to increase the level of adherence to osteoporosis prophylaxis medications in patients with newly diagnosed Polymyalgia Rheumatica/Giant Cell Arteritis (PMR/GCA). <h3>Methods</h3> This is an ongoing 1-year prospective cohort study. 37 consecutive steroid treated patients with newly diagnosed PMR/GCA were included. Patients were seen by the physicians at baseline, 1<sup>st</sup> and 4<sup>th</sup> month, where they were interviewed about their compliance towards osteoporosis prophylaxis medications, i.e. Calcium/Vitamin D supplements and Bisphosphonates (if Tscore ≤−1), using a standardized questionnaire. Patients were therefore categorized as 100%, 50-100%, &lt;50% adherent or non-adherent to the prescribed drugs. Every individual patient were contacted by our nurses one week after treatment initiation, and subsequently one month after physician visit to evaluate the effect of treatment, compliance to the medications and possible drugs side effects. <h3>Results</h3> 85.3% and 75.8% of the patients were completely adherent to their osteoporosis medications at 1<sup>st</sup> and 4<sup>th</sup> months of treatment initiation, respectively. (figure 1) The difference between level of adherence to the osteoporosis medications at 1<sup>st</sup> (=week 4) and 4<sup>th</sup> month (=week 16) was not statistically significant. (P value:0.369). Decreased adherence in the patients was mainly due to forgetfulness. <h3>Conclusion</h3> Compared to the earlier findings we found a higher level of adherence in this group of patients. Nurse-led telephone follow up as well as educating the patients respecting the importance of the osteoporosis medications for preventing steroid related side effects, may enhance and subsequently maintain high level of adherence to the osteoporosis medications. Our findings are in line with our earlier study indicating a high level of adherence to the osteoporosis medications in PMR/GCA patients.<sup>2</sup> <h3>References</h3> [1] Rossini M, et al. Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos Int. 2006;17:914-21. [2] Emamifar A, et al. Level of Adherence to Prophylactic Osteoporosis Medication amongst Patients with Polymyalgia Rheumatica and Giant Cell Arteritis: A Cross-Sectional Study. International Journal of Rheumatology. 2015;2015:783709. <h3>Disclosure of Interests</h3> None declared
SAT0471 HIGH-RESOLUTION MELTING CURVE ANALYSIS: A RAPID AND PRAGMATIC APPROACH FOR SCREENING OF MULTIDRUG RESISTANT OSTEOARTICULAR TUBERCULOSIS (OATB)
Authors: Kusum Sharma, Aman Sharma, Mandeep Dhillon
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Emergence of MDR in extrapulmonary tuberculosis (EPTB) is a major concern in endemic areas. Timely diagnosis and screening of multidrug resistance in patients of Osteoarticular Tuberculosis (OATB) is a challenge. <h3>Objectives:</h3> To evaluate the rpoB gene real time PCR (RT PCR) in synovial fluid/pus samples and its comparison with MPB64 and IS6110 RT PCR for diagnosis of OATB. <h3>Methods:</h3> Real time PCR using IS6110, MPB64 and <i>rpo</i>B genes was carried out in 150 cases of OATB and in100 non TB control group. Out of these, 20 OATB cases were culture confirmed and 130 were clinically suspected cases. Phenotypic susceptibility testing for culture isolates was performed by standard proportion method.DNA extracted from samples of the culture confirmed cases and the suspected OATB cases confirmed by RT PCR were subjected to <i>rpo</i>B and <i>kat</i>G HRM analysis for screening of MDR. <h3>Results:</h3> The sensitivity of <i>rpo</i>B RT PCR, MPB64 RT PCR and IS6110 RT PCR was 86.5%, 86.5% and 76.5% respectively. All RT PCR were negative in the control group thus the specificity was 100%. HRM analysis detected rifampicin resistance in 10 cases of which, 8 (80%) were MDR while 2 (20%) had isolated rifampicin resistance. Of the 13 cases of isoniazid resistance detected by HRM analysis, 8(61.5%) were MDR while 5(38.46%) were isolated isoniazid resistant. HRM analysis detected an additional 4 MDR cases directly from the samples which were negative by culture. Subsequently, results of HRM analysis were confirmed by <i>rpo</i>B sequencing and mutation were observed at codon 531 (60%); 533 (16%); 516 (12%) and 526 (12%). <i>kat</i>G sequencing revealed mutation at codon 315(100%). There was 100% concordance in the results of phenotypic DST, sequencing results and HRM analysis. Conclusion: <i>rpo</i>B and <i>kat</i>G HRM analysis is a promising method in reliable and rapid screening of drug resistance in OATB cases in 90 minutes. <h3>Disclosure of Interests:</h3> None declared
Poverty and survival in targeted immunotherapy clinical trials.
Authors: Kira O'Neil Bona, Yimei Li, Lena Winestone, Kelly D. Getz, Yuan-Shung Huang, Brian Fisher, Ami Vijay Desai, Troy Richardson, Matt Hall, Arlene Naranjo, Tara O. Henderson, Richard Aplenc, Rochelle Bagatell
Journal: Journal of Clinical Oncology (2019)

10034 Background: Whether precision medicine trials—which tailor medical treatment to a patient’s individual tumor characteristics—should include poverty as an outcome predictor is unknown. In Children’s Oncology Group (COG) trials ANBL0032 and ANBL0931, targeted immunotherapy resulted in the single greatest survival improvement for high-risk neuroblastoma (HR NBL) in decades. We utilized the ANBL0032/ANBL0931 cohort to investigate the hypothesis that poverty independently predicts inferior survival outcomes in targeted immunotherapy trials. Methods: We retrospectively analyzed outcome data for patients uniformly treated with immunotherapy on ANBL0032/ANBL0931 at Pediatric Health Information System-associated hospitals. Poverty exposure was a priori characterized at the neighborhood and household level. Neighborhood poverty was defined as living in a ZIP code with a median household income in the cohort’s lowest quartile ( &lt; $35,916 vs. $46,324-$60,947). Household poverty was defined as Medicaid insurance (vs. private/other). Multivariable Cox regression evaluated associations between poverty exposures and event-free (EFS) and overall (OS) survival adjusting for demographic, clinical and tumor variables (ethnicity, hospital clustering, disease response, disease stage, MYCN status). Post-hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. Results: Among 371 patients, 25% lived in high-poverty ZIP codes; 35% were Medicaid-insured; 14% were exposed to both. Only Medicaid was independently associated with inferior EFS (hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.28-2.84, p = 0.001). OS was inferior in children with Medicaid (HR 2.79, 95%CI 1.63-4.79, p &lt; 0.001) and less than complete disease response (HR 1.89, 95%CI 1.004-3.56, p = 0.049). In post-hoc analysis, joint poverty exposure had a more pronounced impact on EFS (HR 2.21, 95%CI 1.48 to 3.30, p &lt; 0.001) and OS (HR 3.7, 95%CI 2.08-6.59, p &lt; 0.001) than Medicaid alone. No other covariate remained significantly associated with survival. Conclusions: Poverty independently predicted inferior EFS and OS among a cohort of neuroblastoma patients uniformly treated with targeted immunotherapy. For the full potential of precision medicine to be realized, future clinical trials should systematically investigate and intervene upon poverty as a significant predictor of survival.
The AAA+ATPase RUVBL2 is essential for the oncogenic function of c-MYB in acute myeloid leukemia
Authors: Elena Armenteros-Monterroso, Lu Zhao, Luca Gasparoli, Tony Brooks, Kerra Pearce, Marc R. Mansour, Joost H. A. Martens, Jasper de Boer, Owen Williams
Journal: Leukemia (2019)
Tumor growth rate in metastatic adrenocortical carcinoma using two-dimensional computer tomography scan.
Authors: Sarah N. Fuller, Ahmad Shafiei, Maran Ilanchezhian, Mohammadhadi Bagheri, Jaydira Del Rivero
Journal: Journal of Clinical Oncology (2019)

e16125 Background: Adrenocortical carcinoma (ACC) is a rare tumor with an incidence of 1.5–2 per million people per year. It has a poor prognosis with an overall 5-year mortality of 75-80%. The treatment of choice for a localized primary or recurrent tumor is radical surgical resection. However, patients with recurrent or metastatic disease are infrequently cured by surgery alone and chemotherapy has limited benefits. Little is known about the growth rate of metastatic lesions or how disease burden varies among patients, which poses a considerable obstacle in patient care as 17–53% of patients present with distant metastases at the time of diagnosis. Most ACC metastases are found in the liver, lung, bone, and retroperitoneum. Methods: This study retrospectively analyzed the growth rate of metastatic ACC lesions in the lung, liver, lymph nodes, and adrenal bed using serial two-dimensional segmentation of computer tomography images from 10 patients seen at the National Institutes of Health. All patients were females (mean age of 61 years; range, 49–70 years) who had an ACC diagnosis for a mean of 7 years (range, 3–14 years). Only lesions that exhibited FGD-PET avidity were included with up to five lesions per organ recorded. Results: Of the 10 patients, 7 showed metastatic disease at primary diagnosis, although all patients developed recurrent and/or distant metastatic lesions throughout the course of their disease (3 patients had lung lesions, 6 had liver lesions, 8 had adrenal bed recurrence, and 5 had lymph node involvement). Compared over a 6-month period without treatment alteration (change in chemotherapy, surgical intervention, or ablation) lung lesions increased by 11.6%, liver lesions decreased by 17.9%, retroperitoneal lesions increased by 69.25%, and lymph node lesions increased by 9.2%. Conclusions: Treatment of metastatic lesions, particularly in the liver, can increase long-term survival. Understanding growth rates of metastatic tumors may lead to improved treatment of patients with ACC.
Genomic landscape of HBV-related hepatocellular carcinoma in south China patients with high mutational frequency of TP53 and TERT promoter.
Authors: Jiazhou Ye, Yinguang Wang, Rong Liang, Xue Wu, Yang Shao, Feixiang Wu
Journal: Journal of Clinical Oncology (2019)

e15670 Background: Development of hepatocellular carcinoma (HCC) is a complex process with accumulations of polygene abnormalities and multi-pathway misregulation. Hepatitis B virus (HBV) exposure can cause liver damage and promote hepatocarcinogenesis via various biological effects. We aimed to investigate the molecular mechanisms underlying the etiology of HBV-related HCC development, and provide new insights into novel molecular targets. Methods: 84 HBV-positive HCC patients from Guangxi Province, South China, who underwent hepatic resection, were enrolled in this study. Genomic alterations were analyzed in pair-matched tumor and adjacent normal tissue using a hybridization capture-based next-generation sequencing (NGS) assay targeting 422 cancer-relevant genes. Results: In total, 691 somatic mutations, 166 copy number variations and 10 gene fusions were detected in 81 (96.4%) of 84 tumor samples. The most commonly mutated gene is TP53 in this cohort (84% of the patients), which is much higher than its frequency in the reported overall HCC patients. TERT promoter has somatic mutations in 32% of the patients, reactivation of which has been implicated in multiple cancer types. Dysfunction in the cell cycle control pathway (TP53, RB1, CCND1, CDKN2A and CCNE1) was dominant, followed by PI3K/AKT cascade (PIK3CA, AKT3, MTOR, TSC1 and TSC2), while genes of WNT signaling pathway (CTNNB1, APC and AXIN2) were mutated at a lower frequency. In addition, 69 variants in 25 DNA damage repair (DDR) genes were identified in 37 (45.7%) patients. Patients with DDR mutations had a higher tumor mutation burden (TMB) than those without DDR mutations. Conclusions: This study revealed a unique genomic landscape of HBV-related HCC. Besides TP53 being the highest mutated gene, a significant fraction of patients was identified with TERT promoter mutations, suggesting that TERT may play a role in HBV-related hepatocarcinogenesis as a novel molecular marker. Furthermore, the most common biological processes affected by HBV status in HCC were cell cycle control, PI3K/AKT and WNT signaling pathways. The possible synergistic effects of HBV in hepatocarcinogenesis warrant further investigations.
Implementation and evaluation of video-based tumor board conferencing in Haiti.
Authors: Joarly Kerwick Lormil, Kayleigh Bhangdia, Ludmila Svoboda, Viergela Pierre, Lori Buswell, Lauren Greenberg, Ruth Damuse, Scott Andrew Triedman, Temidayo Fadelu
Journal: Journal of Clinical Oncology (2019)

e18333 Background: Lack of local oncology specialists remains a challenge in delivering cancer care in low-resource areas. Since 2013, Dana-Farber Cancer Institute has partnered with Zanmi Lasante, a Haitian non-profit to support the oncology department at University Hospital Mirebalais, a tertiary government hospital. In an effort to build local capacity, the partnership established weekly remote tumor boards between US oncologists and Haitian clinicians. For five years, the tumor boards were conducted by phone; they were limited by inconsistent participant engagement and suboptimal sound quality. The goal of the project was to enhance the tumor boards by implementing a video-based system, and to evaluate its feasibility and acceptance. Methods: We conducted a baseline mixed-methods assessment of satisfaction among tumor board participants. We trained participants on the new video-platform (ZOOM) and implemented its use. We conducted weekly surveys over an 18-week period, using a Likert 1-5 scale to assess call quality and satisfaction with discussion. We collected general information about cases and call logistics. Lastly, we conducted a post-implementation survey. Two-sample T-test was used to examine changes in satisfaction scores. Results: Over the study period, 12 calls occurred; six calls were cancelled –due holidays (2), lack of cases (4). A total of 32 cases were presented, an average of 2.67/call. The cases by cancer type were: 75% breast, 9.38% gynecologic, 9.38%, hematologic, and 6.26% others. Baseline overall satisfaction ranking from 11 participants (response rate-RR 78.6%) was 3.18, while post-implementation from 8 participants (RR 66.7%) was 4.24, P-value= 0.0025. Summary of Weekly Calls (Averages). Conclusions: There was improved call quality and overall satisfaction with transitioning to video-based tumor boards. During longer video calls with didactics, Haiti participants noted lower call quality and satisfaction, likely due to low internet-bandwidth. Videoconference tumor boards are feasible in low resource settings.[Table: see text]
<i>BRCA1/2</i> and multigene panel testing among metastatic breast, pancreas, prostate, and ovarian cancer patients.
Authors: Meghna S. Trivedi, VanAnh L Vo, Tarsha Jones, Thomas Silverman, Wendy Chung, Rita Kukafka, Katherine D. Crew
Journal: Journal of Clinical Oncology (2019)

e13160 Background: Given the availability of targeted therapies such as PARP inhibitors, patients with metastatic breast, pancreas, prostate, and ovarian cancer are recommended to have germline genetic testing for hereditary cancer syndromes. Completion of genetic testing among this population is understudied. Methods: We performed a retrospective study of 548 patients with stage 4 breast, pancreas, prostate, and ovarian cancer at diagnosis from January 2013-December 2017 identified in the New York Presbyterian Hospital Tumor Registry at Columbia University Irving Medical Center. Data on socio-demographics, clinical factors, and genetic testing completion and results were collected from the medical record. We conducted descriptive statistics. Results: Our study population had a median age of 66 years (range, 23-97) at diagnosis; 61% female; 50% non-Hispanic white/22% Hispanic/15% non-Hispanic black/5% Asian/7% other; 33% private insurance/16% Medicaid/44% Medicare/7% unknown insurance. Primary cancer was 24% breast, 8% ovary, 61% pancreas, and 7% prostate. Only 38 patients were seen by a genetic counselor (7%) and only 50 (9%) had genetic testing performed. Among those who underwent germline testing, 92% had multigene panel testing (median number of genes tested 13.5, range 2-74). Pathogenic variants were detected in 6 patients (12%), of which 4 had a BRCA1/2 mutation, and 26% had a variant of uncertain significance (VUS). Conclusions: We found that only a small percentage of metastatic breast, pancreas, prostate, and ovarian cancer patients underwent genetic testing. Further research is necessary to identify the barriers to genetic testing uptake in metastatic cancer patients. BRCA1/2 and multigene panel testing has important implications in this patient population not only for treatment decisions, but also to increase cascade testing in unaffected family members who may be at risk for malignancy in the future.