tbuckley/cabot-search huggingface dataset:
Potential role of serial liquid biopsies to guide treatment decisions in NSCLC.
Authors: Todd Cory Knepper, Theresa A. Boyle, Jhanelle Elaine Gray, James Kevin Hicks
Journal: Journal of Clinical Oncology (2018)

e21079 Background: The use of blood based next-generation sequencing (liquid biopsy) to identify genomic alterations (GAs) in patients (pts) with cancer is increasingly widespread. However, there is a paucity of information describing the clinical utility of performing serial liquid biopsies at various time intervals to guide treatment course through the detection of targetable GAs and gain/loss of GAs associated with resistance. This retrospective study assessed the use of serial liquid biopsies in pts with NSCLC to determine the changes in detectable GAs between serial tests and the frequency in which those GAs were targetable or predictive of resistance. Methods: Moffitt’s Clinical Genomic Action Committee database, which curates clinical variables and NGS results, was used to identify pts with NSCLC who had serial liquid biopsies from 9/1/2015 and 11/31/2017. Results: 17 pts with NSCLC had serial liquid biopsies (35 total tests) performed. GAs were detected in 14 pts (82.4%) (median = 4 GAs per test; range = 0-13). The median time between serial sampling was 126 days (range 56 – 564). Of the 14 pts with GAs detected, none of the intra-patient reports were identical. New GAs were detected in 13 (92.9%) pts and GAs were lost in 4 (28.6%). 11 (78.6%) received EGFR TKI’s. 2/11 (18.2%) had known resistance GAs detected on the first liquid biopsy and an additional 3 (27.3%) had known resistance GAs detected on the second liquid biopsy. 6/14 (42.9%) pts had a GA detected on a subsequent liquid biopsy that was potentially targetable with agents on clinical trials or commercially available agents. Conclusions: The results of serial liquid biopsies performed on pts with NSCLC are not static with none having identical results between tests. Serial liquid biopsies revealed clinically important results with known resistance alterations detected on the subsequent test in 27.3% of cases treated with EGFR inhibitors and previously undetected potentially targetable alterations detected in 42.9% of cases. Gene # (%) of pts with GA detected on subsequent testing EGFR 6 (42.9) ERBB2 3 (21.4) RET 3 (21.4) KRAS 2 (14.3) TP53 2 (14.3) BRAF 2 (14.3) PIK3CA 2 (14.3) ALK 1 (7.1) RAF1 1 (7.1) FGFR1 1 (7.1) CDK4 1 (7.1) CCNE1 1 (7.1) NOTCH1 1 (7.1) AR 1 (7.1) NF1 1 (7.1) TSC1 1 (7.1) MET 1 (7.1)
Cumulative burden of chronic disease in adult survivors of childhood cancer: The St. Jude Lifetime (SJLIFE) cohort.
Authors: Nickhill Bhakta, Qi Liu, Kirsten K. Ness, Malek Jawad Baassiri, Hesham Eissa, Frederick Yeo, Wassim Chemaitilly, Matthew J. Ehrhardt, Johnnie Bass, Michael William Bishop, Kyla C. Shelton, Lu Lu, Sujuan Huang, Zhenghong Li, Eric Caron, Jennifer Lanctot, Deo Kumar Srivastava, Melissa M. Hudson, Yutaka Yasui, Leslie L. Robison
Journal: Journal of Clinical Oncology (2016)

10523 Background: A substantial proportion of childhood cancer survivors develop chronic health conditions. However, the cumulative burden (CB) of multiple organ system morbidity among survivors has not been described. Methods: 3026 childhood cancer survivors (mean age 35.3 yrs, range 19-68; time from diagnosis 27.0 yrs, range 11-53) were enrolled in the SJLIFE cohort (eligibility: survived > 10 yrs and > 18 yrs of age) and clinically evaluated for 166 chronic health conditions. Results from prospective and retrospective clinical assessments were used to grade outcomes using a modified Common Terminology Criteria for Adverse Events. Mean cumulative count per 100 survivors was used to estimate CB with 95% confidence intervals (CI). Results: At 35 yrs post-diagnosis the estimated cumulative incidence of survivors experiencing a Grade 1-4 (mild to life-threatening) or Grade 3-4 (severe or life-threatening) chronic condition was 98.5% and 87.2%, respectively. At 35 yrs, the estimated CB was 1,065 (CI 1029-1100) Grade 1-4 conditions per 100 survivors and 300 (CI 285-314) Grade 3-4 conditions per 100 survivors. The CB for Grade 1-4 conditions ranged from 566 per 100 retinoblastoma survivors to 1,741 per 100 CNS survivors (Table). Substantial increases in Grade 1-4 CB occurred from 10 and 20 yrs to 35 yrs post-diagnosis, rising from 138 (CI 131-145) and 417 (CI 401-435) to 1,065 per 100 survivors, respectively. Conclusions: At 35 yrs from initial cancer diagnosis, 99% of survivors will experience at least one chronic condition. However, the true impact of surviving cancer is reflected in the 35 year CB, when it is estimated that, on average, a survivor will experience 11 non-fatal chronic health conditions including an average of 3 severe or life-threatening conditions. N 20 yr. Cumulative Burden (Mean per 100 survivors) 35 yr. Cumulative Burden (Mean per 100 survivors) Grade 1-4 Grade 3-4 Grade 1-4 Grade 3-4 All Cancers 3026 417 107 1065 300 Acute Lymphoblastic Leukemia 1008 294 73 956 255 Acute Myeloid Leukemia 104 543 147 1239 418 Hodgkin 368 481 111 1387 400 Non-Hodgkin 223 309 82 1166 296 CNS 312 989 201 1741 529 Sarcomas 398 479 164 1112 350 Wilms 202 237 59 741 204 Neuroblastoma 138 237 82 723 200 Retinoblastoma 90 158 51 566 198
Abstract P268: Impact of Overweight and Obesity in Prevalence and Management of Hypertension
Authors: Hong Seok Lee, Yong-Moon Park, Kyungdo Han, Jin Hong Yang, Sung Rae Kim
Journal: Circulation (2017)

Background: Obesity defined by body mass index (BMI) and waist circumference (WC) can affect the epidemiology of hypertension differently, however, there were not enough large national wide hypertension studies using two measurements. Some research reported both were associated with diseases including hypertension in a different way such as gender-specifically. So, we will evaluate the prevalence, awareness, treatment, and control of hypertension according to obese status using nationally representative data Materials and Methods: Among adults aged ≥19 years who participated in the Korean National Health and Nutrition Examination Survey between 2008 and 2010, a total of 20,578 subjects (8,777 men and 11,801 women) were analyzed according to BMI and WC. General obesity was defined as BMI ≥ 25 kg/m 2 and abdominal obesity was defined as WC ≥ 90 cm in men and ≥ 80 cm in women, both of which were based on the Asian-pacific criteria. We applied a blood pressure goal of less than 150/90 mmHg for patients 60 years of age or older who did not have diabetes or chronic kidney disease. Patients 18 to 59 years of age without major comorbidities, and those 60 years of age or older who had diabetes, chronic kidney disease, or both conditions, the new blood pressure goal is less than 140/90 mmHg. Results: There was the significant increase in the prevalence of hypertension as BMI and WC increased in both genders. Prevalence of hypertension in men was 21.1%, 30.7%, 39.6%, 51.6% with BMI less than 23 kg/m 2 (normal weight), less than 25 kg/m 2 and more than 23 kg/m 2 (overweight), less than 30 kg/m 2 and more than 25 kg/m 2 (obese grade I), more than 30 kg/m 2 (obese grade II), respectively. Prevalence of hypertension in women was 13.1%, 27.4%, 40.2%, and 49.2% in each BMI group. In addition, a prevalence of hypertension was higher in obese individuals than non-obese individuals in all age groups. In women, awareness increased as BMI and WC increased ( p for trend &lt;0.001), whereas, control rate has been significantly decreased with increasing BMI ( p for trend = 0.02). With increasing WC in women, control of blood pressure among treated persons also tended to decrease ( p for trend = 0.04). However, control rate was not different according to both general and abdominal obese status in men. Compared to those in other age groups, young obese adults less than 40 years had the relatively lower prevalence of hypertension (34.3%) but also had lower awareness (16.8%) and treatment (60.7%). Conclusion: Our findings show that prevalence of hypertension was associated with increasing BMI and WC in both genders, suggesting that obese persons were prone to have hypertension. Control of blood pressure in women was decreased with increasing BMI and WC, suggesting that obese women might be an important target for hypertension control. Lower awareness and treatment of hypertension in young obese adults are not negligible.
Identifying the patient journey and treatment lines patterns in metastatic pancreatic cancer using patient-reported outcomes (PRO) from a digital patient-powered network (PPN).
Authors: Irad Deutsch, Eliran Malki, Raanan Berger, Maytal Bivas-Benita
Journal: Journal of Clinical Oncology (2018)

e16252 Background: Patient-reported outcomes (PRO) address a critical need in value assessment of cancer treatments, outcomes, costs and quality of life (QOL). It is a broad representation of patients and can provide insights that are not available from clinical trials. Belong PPN is a social network for cancer patients and caregivers. It provides patients with access to other patients, healthcare professionals and disease management tools. In this study, we used PRO from the Belong patient-powered network (PPN) to explore the patient journey and treatment lines patterns of metastatic pancreatic cancer (MPC) patients in Israel. Methods: We conducted a retrospective analysis using real-world evidence (RWE) and PRO collected from Israeli users of the Belong PPN. Data included PRO and medical records provided voluntarily and anonymously. The treatment journeys of 75 patients from Israel, diagnosed with MPC between March 2015 and December 2017 were mapped. Specific treatment lines were identified using Belong’s artificial intelligence (AI) engines. Data was validated manually by the research team to assure accuracy. Results: We were able to map the treatment journeys of 88% (n = 66) of the MPC patients. We detected up to 4 treatment lines and identified extreme survivors within this population (n = 3). The data showed us three first-line treatment choices for MPC patients in Israel: FOLFIRINOX, Gemzar (Gemcitabine) and any treatment combination. FOLFIRINOX was the most abundant first-line treatment choice in MPC and was given to 61% of patients. Gemzar alone was used in 18% and different drug combinations in 11% of patients. Eleven percent of the patients received no treatment following their MPC diagnosis and were admitted to best supportive care. Conclusions: Data from patients using the Belong PPN was able to provide insights into the treatment journeys of MPC patients in Israel, the three first-line treatment prevalence and the following lines of treatment. Continuous evaluation of RWE and PRO from the Belong PPN would allow comparative effectiveness research of cancer treatments and lead to improved evidence-based care and patients’ QOL.
Association between microsatellite instability and <i>BRAF</i>, <i>TP53</i>, <i>PTEN</i>, and <i>KRAS</i> mutations in colorectal cancer.
Authors: Maher Albitar, Sucha Sudarsanam, Wanlong Ma, Shiping Jiang, Wayne Chen, Vincent Anthony Funari, Forrest Blocker, Sally Agersborg
Journal: Journal of Clinical Oncology (2018)

e15604 Background: Microsatellite instability (MSI) and DNA mismatch repair defect (dMMR) are dependable predictive biomarkers of colorectal cancer (CRC) response to checkpoint inhibitors. We explored the correlation between mutations in genes encoding various DNA repair proteins and other genes to PD-L1 expression in CRC. Methods: In this study, 264 CRC tissue samples were collected in a community setting and were evaluated for molecular abnormalities. TP53, KRAS, BRAF, and PTEN mutations were detected with next generation sequencing, PTEN deletions with FISH, PD-L1 expression with IHC, MLH1 promoter methylation and MSI with PCR. Correlations were evaluated using standard statistical Chi Square and Kruskal-Wallis tests. Results: MSI in CRC correlated directly with age (P < 0.0001), MLH1 promoter methylation (P < 0.0001), and BRAF mutation (P < 0.0001), and inversely with PTEN (P < 0.0001), KRAS (P = 0.002), and TP53 (P = 0.005) mutations. PD-L1 expression directly correlated with MSI (P = 0.0047), MLH1 promoter methylation (P = 0.004), and BRAF mutation (P < 0.0001). There was no correlation between PD-L1 expression and TP53 or KRAS mutations. Conclusions: CRC has been shown to express immune checkpoint proteins differently than other cancers. While PD-L1 expression may not be a good predictor of response to checkpoint inhibition, MSI predicts benefit well. The demonstration of a direct correlation between MSI and BRAF and PTEN mutation suggests that therapy targeting these abnormalities may be effective when combined with checkpoint inhibitors. Prevalence and Correlations of Mutations, MSI, and PD-L1 Prevalence Mutant or Expressing MSI Type of correl. PD-L1 Pvalue Pvalue Age N/A 0.04 Positive NS PD-L1 24.9% ( 56/225) 0.005 Positive 0.005 KRAS 52.4% (129/246) 0.002 Negative NS TP53 58.9% (145/246) 0.005 Negative NS BRAF 15.1% ( 31/205) of PD-L1 samples 9.8% ( 21/215) of MSI samples < 0.0001 Positive 0.004 KRAS +/or TP53 81.3% (200/246) < 0.0001 Negative N/A K/RAS 52.4% (129/246) KRAS 0.001 Negative NS MLH1 promoter methylation 20.7% ( 28/135) of PD-L1 samples 23.6% ( 56/237) of MSI samples < 0.0001 Positive 0.01 PTEN Mutation 5.7% ( 14/246) < 0.0001 Positive 0.007
Impact of prior pelvic bone marrow irradiation on toxicity of oxaliplatin-based chemotherapy in rectal cancer.
Authors: Mateusz Spalek, Wojciech Michalski, Krzysztof Bujko, Lucjan Wyrwicz
Journal: Journal of Clinical Oncology (2018)

e15706 Background: Radiotherapy is used in the neoadjuvant setting in majority of rectal cancer patients in order to improve local control in patients with threatened resection margin. Preoperative pelvic irradiation might damage bone marrow and in consequence, relative dose intensity (RDI) and efficacy of further systemic chemotherapy (CT) might be reduced. The aim of the study was to assess whether radiation damage to the pelvic bone marrow influences the tolerance of further oxaliplatin-based CT. Methods: We have performed the cohort analysis of patients with adenocarcinoma of rectum or colon receiving FOLFOX-4 chemotherapy in neoadjuvant, adjuvant or palliative setting between 2011-2016 in M Sklodowska Curie Memorial Cancer Center. Oxaliplatin RDI within 8 and 16 weeks from the beginning of CT was calculated for each patient. The major factors, which can reduce oxaliplatin RDI, were analyzed independently (hemathological toxicity, neurological toxicity, occurrence of hypersensitivity reactions to oxaliplatin). The data regarding the first disruption of oxaliplatin dose within all planned courses of FOLFOX-4 was also collected. The pelvic bone marrow volume within radiation field was calculated for all patients. Results: 220 patients met eligibility criteria. 41 of them received neoadjuvant radio(chemo)therapy (study group), the remaining 179 patients were assigned to control group (n = 179). 8-weeks oxaliplatin RDI did not differ significantly between irradiated and non-irradiated patients (p = 0.794). There were no statistically significant differences in observed oxaliplatin-related toxicities. The median time between the start of chemotherapy and the first disruption of oxaliplatin administration was also not statistically different between the two groups (p = 0.156). The consistent observations were performed for 16-weeks time frame. Conclusions: An impact of preoperative radio(chemo)therapy on RDI for oxaliplatin or tolerance of FOLFOX in general was not found in this cohort of patients.
Survival of patients with pancreatic cancer II-IV stages depending on the stage, regimen used in the first line.
Authors: Kristina A. Novoselova, Liubov Yu Vladimirova, Natalya A Abramova, Anna E Storozhakova, Irina L. Popova, Natalya Mikhailovna Tikhanovskaya, Ludmila A. Ryadinskaya, Aza A. Lyanova, Tatyana A. Snezhko, Sergey N. Kabanov, Irina A. Zhuzhelenko, Elena Aleksandrovna Kalabanova, Jana V. Svetickaja, Irina Kornilova, Nataliya Samaneva, Marina M. Sergeeva, Georgy Salamov
Journal: Journal of Clinical Oncology (2018)

e16211 Background: The purpose of the study was to analyze the survival of patients with pancreatic cancer II-IV stages depending on the regimen used in the first line. Methods: The data of adults treated in 2013-2017 were studied. OS was calculated using the Kaplan Meier method and the log-rank test. Results: 133 pts were recruited: stage IIA – 26 (19.6%), IIB – 32 (24.1%), III – 29 (21.8%), IV – 46 (34.6%). The median survival was 7 mon (95% CI 1-11.8). The 36-month cumulative survival rate (CSR) was 0.2, and the 60-mon CSR – 0. Probability of surviving past 22 mon was 0.22, the standard error 0.09; past 12 mon – 0.45, the standard error 0.08. OS was associated with surgical treatment: 20-mon CSR with surgery – 0.25, without surgery – 0.4; 36-mon CSR – 0.25 and 0, respectively (p = 0.017). The median survival – 7 mon (95% CI 6.4-12.4) and 6 mon (95% CI 6.5-13.7), respectively. The median survival in st IIA was 6 mon (95% CI 4.2-12.3), IIB – 8 mon (95% CI 5.5-18.9), III – 6.5 mon (95% CI 4.1-14.8), IV - 6 mon (95% CI 4.7-13.7). 20-mon CSR in st IIA was 0.75, IIB – 0.4, III – 0.43, IV – 0.15 (p = 0.05). OS depended on the first-line therapy: 20-mon CSR in GEM/GEMCAP – 0.35 (median survival 6.5 mon, 95% CI 6.3-11.1), GEMOX – 0.28 (median survival 9 mon, 95% CI 6.2-16.8), FOLFOX/OXCAP/Capecitabin – 0.18 (median survival 3.5 mon, 95% CI 9.9-33.6), FOLFIRI/FOLFIRINOX – 0.36 (median survival 8 mon, 85% CI 8.5-33.2) (p = 0.01). Conclusions: The highest OS was registered in undergone surgery pts, pts with IIA stage of the disease and in pts with GEM/GEMCAP or FOLFIRI/FOLFIRINOX as the first-line therapy.
Clinical characteristics and EGD surveillance in Lynch-syndrome patients with small bowel/duodenal carcinomas.
Authors: Deepak B. Vangala, Christian Pox, Swetlana Ladigan, Christoph Engel, Robert Hueneburg, Claudia Perne, Verena Steinke-Lange, Nils Rahner, Hans K. Schackert, Matthias Kloor, Stefanie Holzapfel, Judith Kuhlkamp, Christian Strassburg, Monika Morak, Elke Holinski-Feder, Reinhard Büttner, Stefan Aretz, Markus Loeffler, Wolff H. Schmiegel, Karsten Schulmann
Journal: Journal of Clinical Oncology (2018)

1555 Background: Small bowel carcinomas (SBC) account for less than 5% of all gastrointestinal malignancies in the general population. However in patients with Lynch-Syndrome (LS) the life-time-risk for SBC is reported as high as 10%. The aim of this study was to evaluate the effectiveness of esophago-gastro-duodenoscopy (EGD) surveillance for early detection of proximal SBCs. Methods: The German Consortium for Intestinal Cancer database was screened for patients with a diagnosis of SBC. General tumor characteristics such as mutational status and age specific incidence where analyzed. Tumor stage at diagnosis was used as a surrogate parameter for prognosis and correlated to patients being diagnosed by symptoms compared to patients diagnosed by EGD-surveillance. Furthermore, adherence to EGD-surveillance after SBC diagnosis was correlated to survival. Statistics were calculated using Fisher’s exact test. Results: A total of 125 SBC in 112 patients were included in the study (45.6% duodenal, 32% jejunal, 10.4% ileal, 9.6% unclassified). The median age at diagnosis was 51.7 years (15.1 – 80.7) with 62% of patients being male. MLH1 and MSH2 germline mutations were most prevalent with 37 % each. Of all SBCs, 10.4% of patients were younger than 35 years at diagnosis (8.8 % of duodenal cancers). Duodenal cancer patients undergoing surveillance were diagnosed with early stage disease (UICC I-IIa) significantly more often than patients diagnosed because of symptoms (69.2 % vs 26.6%; p = 0.0089). In non-duodenal SBC there was no stage difference between these groups. Adherence to EGD surveillance was better after SBC diagnosis with significantly less cancer deaths among patients undergoing surveillance after SBC. Conclusions: To our knowledge, this is the largest study regarding the role of EGD surveillance for early detection of SBC in LS patients. Our data support the use of EGD as a surveillance instrument for duodenal cancer, which make up nearly half of SBC in LS patients. In contrast to current practice in Germany, the results of this study suggest an earlier beginning of EGD surveillance than at the age of 35.
Conflicts of interest in infection prevention and control research: no smoke without fire. A narrative review
Authors: Mohamed Abbas, Daniela Pires, Alexandra Peters, Chantal M Morel, Samia Hurst, Alison Holmes, Hiroki Saito, Benedetta Allegranzi, Jean-Christophe Lucet, Walter Zingg, Stephan Harbarth, Didier Pittet
Journal: Intensive Care Medicine (2018)

Conflicts of interest (COIs) do occur in healthcare research, yet their impact on research in the field of infection prevention and control (IPC) is unknown. We conducted a narrative review aiming to identify examples of COIs in IPC research. In addition to well-known instances, we conducted PubMed and Google searches to identify and report case studies of COIs in IPC and antimicrobial resistance (AMR), which were chosen arbitrarily following consensus meetings, to illustrate different types of COIs. We also searched the Retraction Watch database and blog to systematically identify retracted IPC and/or infectious disease-related papers. Our review highlights COIs in academic research linked to ties between industry and physicians, journal editors, peer-reviewed journals' choice for publication, and guideline committees participants and authors. It explores how COIs can affect research and could be managed. We also present several selected case studies that involve (1) the chlorhexidine industry and how it has used marketing trials and key opinion leaders to promote off-label use of its products; (2) the copper industry and how reporting of its trials in IPC have furthered their agenda; (3) the influence of a company developing "closed infusion systems" for catheters and how this affects networks in low- and middle-income countries and guideline development; (4) potential perverse incentives hospitals may have in reporting healthcare-associated infection or AMR rates and how government intervention may restrict AMR research for fear of bad publicity and subsequent negative economic consequences. Finally, the analysis of reasons for the retraction of previously published papers highlights the fact that misconduct in research may have other motivations than financial gain, the most visible form of COIs. COIs occur in the field of research in general, and IPC and AMR are no exceptions. Their effects pervade all aspects of the research and publication processes. We believe that, in addition to improvements in management strategies of COIs, increased public funding should be available to decrease researchers' dependency on industry ties. Further research is needed on COIs and their management.