tbuckley/cabot-search huggingface dataset:
Prognostic impact of MSI in stage II colon cancers: An additional translational study of the SACURA trial.
Authors: Toshiaki Ishikawa, Megumi Ishiguro, Eiji Nakatani, Hiroyuki Uetake, Hideki Ueno, Kenta Murotani, Shigeyuki Matsui, Naohiro Tomita, Yasuhiro Shimada, Keiichi Takahashi, Kenjiro Kotake, Masahiko Watanabe, Hidetaka Mochizuki, Satoshi Teramukai, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2017)

e15155 Background: The SACURA trial is a phase III study to evaluate the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone for stage II colon cancer. Superiority of adjuvant treatment with UFT to surgery alone was not demonstrated (ASCO2016 abst#3617). In an additional translational study, we assessed microsatellite instability (MSI) status of cancer tissues and prospectively examined the association of MSI with prognosis in stage II colon cancer patients. Methods: Formalin-fixed, paraffin-embedded samples were prospectively collected from 1026 patients enrolled in the SACURA trial. MSI was evaluated using 5 markers; BAT25, BAT26, D2S123, D5S346, and D17S250. MSI-high (MSI-H) was defined as the presence of instability in more than 20% of the markers. Median follow-up time was 69.6 months. Results: MSI-H, MSI-low (MSI-L) and microsatellite-stable (MSS) was observed in 74 (7.2%), 24 (2.3%), and 928 (90.5%) samples, respectively. Patients with MSI-H was significantly frequent in female, right-sided colon cancers, &gt; 5cm tumors, poor histological type, and elevated CEA. Relapse rate for MSI-H patients (4.1%) was significantly lower than that for MSI-L/MSS cancer (13.4%, p = 0.02). Relapse free survival (RFS) in MSI-H patients was significantly better than in MSI-L/MSS patients (hazard ratio: 0.40, 95%CI: 0.17-0.98, p = 0.045), as well as adjusted results by prognostic factors. The 5-year RFS rates in MSI-H and MSI-L/MSS patients were 92.9% and 84.1%, respectively. Although there was no statistical significance, the 5-year RFS rate in MSI-H patients was tended to be better than that in MSI-L/MSS patients in the surgery alone group (94.3% vs. 83.1%, p = 0.086) as well as in the UFT group (91.7% vs. 85.1%, p = 0.233). Conclusions: MSI was an independent prognostic factor in stage II colon cancers. By considering their favorable RFS, adjuvant chemotherapy for stage II colon cancer patients with MSI-H may be unnecessary. Clinical trial information: NCT00392899.
Survival impact of adjuvant regimens for advanced gastric cancer after radical D2 resection in a Peruvian population.
Authors: Patricia Elizabeth Rioja, Daniel Enriquez, Christian Pacheco, Zaida Morante, Andres Guevara, Victor Castro, Paola Catherine Montenegro, Eduardo Payet
Journal: Journal of Clinical Oncology (2017)

e15576 Background: The benefit of chemoradiotherapy(CRT) or chemotherapy (CT) for gastric cancer with high metastatic lymph node involvement after complete radical D2 resection is still controversial, previous studies had reported better disease free survival (DFS) but no differences in overall survival (OS). Our aim was to compare DFS and OS between CRT and CT. Methods: Retrospectively, 201 medical records were reviewed from patients with advanced gastric cancer (nodes +ve) after complete radical D2 resection between 2008 and 2012 at Instituto Nacional de Enfermedades Neoplasicas (Peru). Patients received CRT (5FU and RT as Macdonald’s protocol) or CT (capecitabine 2g/m2/14days + oxaliplatin 135mg/m2/day1 q21d for 6months). We describe clinical and pathological characteristics, DFS/OS with univariate and multivariate cox analysis were performed. Results: Mean age was 54.4years [19-83] and 17.9% were &lt; 40years. Distal localization (46%), high histological grade (69.7%) and poorly cohesive subtype (38.3%) were most frequent characteristics among patients, 140(69.7%) and 130(64.7%) were T4 and N3, respectively. From 201 patients, 134 underwent to CRT and 67 to CT, with no clinical differences between groups. We observed a significant higher nodal ratio in CT group (0.27 vs 0.35, p = 0.009). 69.5% patients completed treatment with CRT, while only 54.5% in CT (p = 0.04). At 5years median of follow-up, 66 (49.3%) and 26(38.8%) recurrences were documented in CRT and CT groups, respectively. Median DFS were 19 and 23 months in CRT and CT group (HR:1.04, 95%CI:0.7-1.4, p = 0.8), while median OS were 25 and 26 months, respectively (HR:1.07, 95%CI:0.75-1-5, p = 0.6). At multivariate analysis, higher T stage and nodal ratio were associated to worse DFS, and patients who completed treatment were associated to better DFS (HR:0.59, 95%CI:0.4-0.8, p = 0.004). Higher T stage and nodal ratio had significant negative impact on OS. Conclusions: We found a benefit of CT over CRT in gastric cancer with high metastatic lymph nodes, however in our population it was not statistically significant, indeed further larger clinical trials are needed. In this study, higher T stage and nodal ratio were associated to worse prognosis.
TCT-76 Long-term outcomes following transcatheter tricuspid valve repair with the FORMA system
Authors: Lluis Asmarats, Gidon Perlman, Fabien Praz, Mark Hensey, Michael Chrissoheris, François Philippon, Jian Ye, Rishi Puri, Philippe Pibarot, Adrian Attinger, Robert Moss, Elisabeth Bédard, Aris Moschovitis, Sandra Lauck, Philipp Blanke, Jonathon Leipsic, Konstantinos Spargias, Stephan Windecker, John Webb, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2018)
A quality improvement project to address oncofertility in children and adolescents with cancer: Development of an oncofertility roadmap.
Authors: Lindsay Hoogenboom, Rachel Phelan, Neel Bhatt, Sarah K. Dobrozsi
Journal: Journal of Clinical Oncology (2018)

e18536 Background: Cancer treatment has known effects on male and female fertility. Governing bodies advocate for fertility counseling prior to initiation of chemotherapy; however there is no standard recommendation to address this throughout cancer treatment. Rates and documentation of fertility discussions remain suboptimal, with barriers related to patient factors (poor prognosis), physician discomfort, time constraints, and lack of institutional resources or guidelines. The objective of this quality improvement (QI) project was to 1) identify institutional barriers to fertility counseling; and 2) develop a roadmap to standardize counseling for pediatric oncology patients before, during, and after therapy. Methods: As part of an institutional QI project to standardize education to newly diagnosed pediatric oncology patients, a multidisciplinary team of physicians, advanced practice providers, nurses, and psychologists reviewed literature, mapped current practice, and identified gaps. Expertise was provided by reproductive medicine and endocrinology disciplines. Knowledge was synthesized to create a roadmap to define options available to patients, clarify referral process, and clarify provider roles. This delineated time points before, during and after cancer treatment with recommendations for monitoring and counseling. Results: Institutional barriers to fertility counseling are: 1) provider confusion with fertility preservation options; 2) no standard approach to counseling or monitoring; 3) inadequate institutional referral guidelines; and 4) unclear delegation of roles amongst providers. Roadmaps addressed these barriers and the needs of pre- and post-pubertal males and females. Training sessions and documents were created to improve provider comfort with content. Conclusions: Development of roadmaps to address fertility preservation from diagnosis through survivorship is a necessary step to standardize and improve practice. Opportunity remains for continued refinement using standard QI methodology and measured patient outcomes. We believe that publishing these roadmaps can help other institutions to apply similar QI processes.
Concordance between comprehensive cancer genome profiling in plasma and matched tumor specimens.
Authors: Roopika Menon, Judith N Müller, Markus Falk, Sotirios Lakis, Erika Mariotti, Frauke Leenders, Miriam Bertrand, Nicole Neemann, Maria Netchaeva, Lukas C. Heukamp, Christian Gloeckner, Markus Tiemann, Johannes Heuckmann, Frank Griesinger
Journal: Journal of Clinical Oncology (2017)

e23146 Background: The importance and clinical use of liquid biopsies to identify somatic, targetable alterations in the plasma of cancer patients is steadily increasing. However, their concordance with alterations identified in cancer specimens tested in routine diagnostics is not being monitored. In a cohort of non-squamous cell lung cancer patients, our aim was to systematically compare alterations found by a massively parallel sequencing liquid biopsy assay covering 39 cancer related genes (NEOliquid) with alterations identified by routine diagnostics in a certified central pathology laboratory. Methods: Routine Diagnostics: DNA mutational analysis was performed using cobas or Sanger-Sequencing. Rearrangements were identified using immunohistochemistry or FISH. NEOliquid assay: Cell-free DNA from plasma was subjected to hybrid-capture based next-generation sequencing to detect point mutations, small insertions and deletions, copy number alterations and genomic translocations in 39 clinically relevant genes in a single assay. To evaluate and compare the performance of liquid biopsies, we applied the NEOliquid tests on blood samples of 82 non-squamous NSCLC patients and correlated them with results of routine diagnostics of matched tissue samples. Results: Routine diagnostics for lung cancer related oncogenes (EGFR, ALK, ROS1, KRAS, BRAF) identified a total of 50 somatic alterations of which 37 were point mutations, 11 InDels and 2 gene fusions. NEOliquid analysis of the corresponding plasma sample revealed a total of 34 alterations, including 21 targetable driver alterations. Overall, the concordance of mutation calls between routine diagnostic testing and NEOliquid was 97.6%, with a sensitivity of &gt; 70% and a specificity of 100%. Importantly, NEOliquid identified additional clinically relevant genomic alterations, not covered by routine testing. Conclusions: We have shown high concordance of genomic alterations identified from liquid biopsies and tumor tissue specimens. The excellent specificity of actionable alterations identified by NEOliquid offers analytical performance for routine diagnostic use.
Evaluation of the concordance between the stage of the disease and Ki-67 proliferation index in GEP-NETs.
Authors: Veli Berk, Ersin Ozaslan
Journal: Journal of Clinical Oncology (2016)

e15646 Background: To demonstrate the degree of concordance between TNM staging used in the determination of the prognosis ofgastroenteropancreatic neuroendocrine tumor(GEP-NET) patients and Ki-67 proliferation index value used in the grading of these tumors and investigate the most reliable prognostic parameter among them. Methods: The medical files of the patients with GEP-NET were retrospectively examined and demographic characteristics, survival times, grade of these tumors and histopathologically detected Ki-67 values, microscopic and macroscopic histopathological characteristics were recorded and evaluated statistically. Results: Patient population consisted of 72 (51.1%) female and 69 (48.9%) male. The most frequently seen primary sites were stomach (33.3%), then in decreasing number of frequency pancreas (27%), colon-rectum (15.6%), small intestine (12.8%) and appendix (11.3%). The GEP-NET of the patients was in Grade 1 (G1) (n:103; 73%), Grade 2 (G2) (n:24; 17%) and Grade 3 (G3) (n:14; 10%). The GEP-NET of the patients was of Stage 1 (n:66; 46.8%), Stage 2 (n:14; 9.9%), Stage 3 (n:12; 8.5%) and Stage 4 (n:49; 34.8%). In statistical analysis performed, Ki-67 increased in parallel with the stage of the disease (p < 0.001). Statistically significant differences were detected between Stages 1 and 4 and also Stages 2 and 4 in terms of Ki-67 values (p < 0001). Five-year survival rates of the patients were 88% in G1, 44% in G2 and 24% in G3. Survival rates of Stage 4 patients were 5.6 times lower relative to Stages 1 and 2 patients, respectively (p < 0.001). Median 5-year survival rates of the patients were 90% in Stage 1, 100% in Stage 2, 47% in Stage 3 and 46% in Stage 4. In univariate analysis, age of the patients, grade, stage of the tumor and lymph node metastases were found to be parametres effective on overall survival. Conclusions: Decrease in average survival rate in parallel with an increase in the grade of the tumor was more prominent when compared with decrease in survival rates in accordance with increase in stage of the tumor. This phenomenon shows us that in the prediction of prognosis in patients with GEP-NET, Ki-67 value can be more important evaluation factor relative to staging.
Feasibility intervention to increase exercise outcome expectations among breast cancer survivors.
Authors: Rachel Hirschey, Wei Pan, Gretchen Genevieve Kimmick, Marilyn Hockenberry, Ryan Shaw, Isaac Lipkus
Journal: Journal of Clinical Oncology (2017)

e21584 Background: Exercise is associated with decreased mortality and recurrence risk and improved quality of life for breast cancer survivors (BCS). Roughly 1/3 of BCS exercise enough to experience these benefits. A promising strategy to increase exercise among BCS is to target outcome expectations (OEs), or what one expects to obtain or avoid from a behavior. OE dimensions include 1) importance – value placed on the outcome(s); 2) certainty - perceived probability outcome(s) will occur; and 3) accessibility – the frequency with which outcome(s) are considered. Methods: This RCT tested the feasbility and effects of a self-directed booklet designed to increase OEs and exercise. It was created in collaboration with BCS who successfully use exercise to manage long term side effects. OEs were measured through online surveys and exercise was measure with a Fitbit accelerometer. Data was collected at baseline, 4, 8 and 12 weeks post intervention. Feasibility was defined as the extent to which participants made use of intervention materials and was assessed through 9 researcher related questions. Results: The sample is mean age of 58, 74% white, 26% black, an average 2.5 years post treatment and about 1/3 take an AI or SERM. The booklet “somewhat” (mean = 3.24, SD = 1.8 on 1-5 Likert scale) made use of the booklet, as intended. OEs increased 0.01 points over time in the intervention arm, compared to the control arm ( p = 0.3555); 0.4 points more for black participants compared to white ( p = 0.0003); 0.2 points per every unit of increased exercise self-efficacy ( p &lt; 0.0001), and 0.01 points per month participants were closer to their time of cancer surgery ( p = 0.0037). Intervention arm participants increased their weekly steps by 970, every 4 weeks, compared to participants in the control arm ( p = 0.0283). Conclusions: Overall the intervention was well received by participants, had positive effects on OEs and exercise and can easily be translated into practice with need for minimal resources. Significant differences were noted for black compared to white participants, thus it is necessary to understand racial differences in exercise beliefs when designing future exercise interventions. Clinical trial information: NCT02348710.
Letter by Hnid Regarding Article, “Low-Calorie Vegetarian Versus Mediterranean Diets for Reducing Body Weight and Improving Cardiovascular Risk Profile: CARDIVEG Study (Cardiovascular Prevention With Vegetarian Diet)”
Authors: Karim Hnid
Journal: Circulation (2018)

I read with great interest the article by Sofi and colleagues 1 about the CARDIVEG trial.I congratulate the authors for their prophylactic work, which effectively contributes to the fight against cardiovascular disease worldwide.Synergistic and interactive combinations of nutrients in Mediterranean diets confer a beneficial effect against cardiovascular disease. 1,2Lacto-ovo vegetarian diets also contribute to lower obesity, lower blood pressure, and decreased incidents of diabetes mellitus. 1,2This study compares the 2 diets in terms of primary and secondary outcomes.I think that an essential factor of both diets is pesticide residues, the causalities of which in relation to cardiovascular morbi-mortalities and diabetes mellitus have been confirmed, and these could interfere with these results. 3Pesticides are widely used in food production to control pests.This standard agricultural practice of using plant-protection products cannot protect food from pesticide residues, which create a health risk to consumers and animals. 3,4All treated food can transmit harmful chemical products resistant to biotic and abiotic degradation to humans through pesticide residues. 3,4ndeed, food contamination has been a worldwide public health concern, and the contaminations of food with pesticides is an important subject for scientific researchers in their respective studies. 3This has contributed to the fact that several countries impose draconian measures to limit those contaminations.However, in the United States, where the Food and Drug Administration is uncompromising, the 2004 study of National Health and Nutrition Examination Survey (NHANES) data 5 by Dana B. Barr and colleagues clearly showed that 70% of children presented detectable levels of ≥1 pesticide, of which the essential source was diet.Therefore, integrating an analysis of patients' pesticide residue levels, and including above-normal levels as study exclusion criteria, would have allowed a better performance of both diets in terms of primary and secondary outcomes.
Leukotriene B4 receptors as a therapeutic target for triple-negative breast cancer
Authors: A.I. Kalinkin, V.V. Strelnikov, E.O. Ignatova, T.V. Kekeeva, M.V. Nemtsova, D.V. Zaletaev, E.V. Poddubskaya, E.B. Kuznetsova, A.S. Tanas
Journal: Annals of Oncology (2018)

Background: Lipid mediators of inflammation, leukotrienes, are involved in tumour development and progression. Leukotriene B4 receptors 1 and 2 (LTB4R and LTB4R2) have been suggested to regulate tumor progression by promoting cell proliferation, survival, migration and metastasis. LTB4R2 was reported to increase invasiveness of breast cancer (BC) cells through IL-8 (interleukin-8) pathway. The inhibitors of leukotriene receptors have been suggested for use in anti-cancer therapy. Methods: We conducted Xma1-RRBS (Reduced Representation Bisulfite Sequencing) protocol for genome-wide DNA methylation assessment on 170 BC samples and 10 normal breast tissue samples as a reference material. Methylation status was determined by Bismark software, and identification of epigenetic BC molecular subtypes was carried out using hierarchical cluster analysis. Results: One of the BC epigenetic subtypes identified by genome-wide DNA methylation analysis appeared to be enriched with triple-negative breast cancer (TNBC) samples demonstrating LTB4R and LTB4R2 genes abnormal demethylation that is potent of initiating ectopic gene expression. Bisulfite Sanger sequencing has confirmed abnormal demethylation of the cytosine residues at positions +117, +121, +148, +184 and +186 relative to the LTB4R transcription start site. Conclusions: By the present day no diagnostic panels to assess the methylation status of leukotriene B4 receptors have been published. Fine mapping of abnormal DNA methylation in the genomic region adjacent to LTB4R and LTB4R2 genes reported here allows development of a simple methylation sensitive PCR laboratory test that would identify tumours prone to leukotriene B4 receptors ectopic expression and thus potentially responsive to their inhibitors. An easy means to select such tumours promotes clinical trials aimed to improve TNBC individualized therapy by introducing the inhibitors of leukotriene receptors as anticancer agents. Legal entity responsible for the study: Research Center for Medical Genetics RAMS. Funding: Russian Science Foundation (project No.18-15-00430). Disclosure: All authors have declared no conflicts of interest.
Cost-effectiveness analysis of cytoreductive surgery and HIPEC compared to systemic chemotherapy in isolated peritoneal carcinomatosis from metastatic colorectal cancer.
Authors: Trevor D Hamilton, Howard John Lim, Andrea J MacNeill, Myriam Hunink
Journal: Journal of Clinical Oncology (2018)

e18897 Background: Cost-effectiveness evaluations of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for the treatment of peritoneal carcinomatosis (PC) from metastatic colorectal cancer (mCRC) in the United States are lacking. Methods: We developed a Markov Model to evaluate the cost-effectiveness of CRS/HIPEC compared to systemic chemotherapy for isolated PC from mCRC from the societal perspective in the United States. Systemic treatment regimens consisted of FOLFOX, FOLFIRI, bevacizumab, cetuximab and pantitumumab. Model inputs including costs, probabilities, survival, progression and utilities were taken from the literature. The cycle length for the model was 2 weeks and the time horizon was 7 years. A discount rate of 3% was applied. The model was tested for internal/external validation and robustness was established with univariate sensitivity and probabilistic sensitivity analyses (PSA). Primary outcomes were total costs, quality-adjusted life years (QALY), life-years (LY), and incremental cost-effectiveness ratio (ICER). A willingness-to-pay (WTP) threshold of $100,000/QALY was assumed. Results: The ICER for treatment with CRS/HIPEC compared to systemic chemotherapy was $91,034/QALY gained ($74,098/LY gained). On univariate sensitivity analysis, total costs for treatment with CRS/HIPEC had the largest effect on the calculated ICER. CRS/HIPEC was a cost-effective strategy over the majority of simulations in the PSA. The average ICER of from 100,000 simulations in the PSA was $70,807/QALY gained. The likelihood of CRS/HIPEC being a cost-effective strategy at the WTP threshold was 87%. Conclusions: CRS/HIPEC is a cost-effective treatment for isolated PC from mCRC in the United States.