tbuckley/cabot-search huggingface dataset:
Exercise and reduced breast cancer risk: A multinational study
Authors: Luke Ratnasinghe, Michael Seddon, Rama Modali, Teresa Lehman
Journal: Cancer Research (2008)

3083   Exercise and physical activity are modifiable risk factors for cancer. There is little data evaluating the relationship between exercise and breast cancer risk comparing different ethnic groups. We evaluated the association between exercise and breast cancer risk among 1468 breast cancer cases and 4865 non-cancer controls in the Global Epidemiology Study (GES). The GES is a multinational study to assess disease risk factors with subjects recruited from countries including the United States, Tunisia and Poland. The GES is linked to the Global Repository® that houses biomaterial including blood, serum, DNA, RNA, frozen tissue, formalin-fixed paraffin embedded tissues, and pathology slides. For breast cancer, newly diagnosed subjects provided informed consent and were asked about exercise activity during in-person interviews. The same survey instrument was used for all subjects in this study, following translation to the local language. For all subjects combined, the multivariate-adjusted adds ratio (OR) was 0.5 (95% confidence interval (95% CI): 0.4-0.7) for women who exercised once per week or more after adjusting for age, race, BMI and packyears of smoking. All ethnic groups in the study population, Caucasian-Americans, African-Americans, Hispanic-Americans, Tunisian-Arabs, and Polish-Caucasians, were at 50% or greater reduced risk for breast cancer if they exercised once or more per week. Women who exercised 4 times per week or more did not gain any additional reduced breast cancer risk. The amount of time spent exercising per session was also significantly associated with reduced breast cancer risk. Women who exercised 15 minutes per session or more were at 40% or greater reduced risk for breast cancer (OR 15-30 mins: 0.5 (95% CI: 0.4-0.7, OR greater than 30 Mins: 0.6 (95% CI 0.5-0.7) in the multivariate model compared to women who exercised less than 15 minutes. Results from our study shows that regular exercise has the potential to reduce breast cancer risk among all women regardless of race.
Pazopanib therapy for adolescent and young adult desmoid tumors.
Authors: Laura Agresta, Rajaram Nagarajan, Sara Szabo, Brian Turpin, Hee Kim, Joel Sorger, Joseph Gerald Pressey
Journal: Journal of Clinical Oncology (2017)

10547 Background: There is a lack of reliably effective medical therapies for desmoid tumors (DT). Surgical resection may be morbid, and even a complete resection does not preclude recurrence. Radiotherapy is associated with potentially severe late-effects, a risk that may be particularly detrimental in young patients. In a previous review of our single institution DT experience, we found that objective treatment responses to medical therapies were rare.However,we have recently observed promising effect from therapy with the tyrosine kinase inhibitor pazopanib in adolescent and young adult (AYA) patients with DT. Methods: Retrospective single institution chart review evaluating all pazopanib treatment in AYA patients with DT. Results: Five AYA patients, ages 15-21 years, with previously treated DT received pazopanib. Four patients with sporadic DT were documented by next generation sequencing to have mutations of CTNNB1, and 1 patient with intra-abdominal tumors following colectomy was known to carry a large germline interstitial chromosomal deletion (5q21.2q23.1) including the APC locus. The median duration of pazopanib treatment was 6 months at the time of analysis (range: 5-21), with treatment ongoing for 4 patients. None of the patients demonstrated progressive disease while on treatment. Best responses by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) were partial response in 3 of 5 and stable disease in 2 of 5 cases. One response was nearly complete. In one case of stable disease, tumor necrosis was evident on magnetic resonance imaging after 2 months on pazopanib. Four patients reported pain relief while on pazopanib, including one patient with stable disease. Pazopanib was discontinued in 1 patient after 18 months due to recurrent facial edema. Other grade 1-2 adverse effects responded to dose reduction. The only grade 3 adverse effect was increasing weakness in a patient with pre-existing myopathy; this patient tolerated pazopanib at a reduced dose. Conclusions: This is the first report of objective responses to pazopanib by RECIST criteria in AYA patients with DT. Given these benefits and relatively mild toxicity, we conclude that pazopanib therapy should be considered in this patient population.
Genome-wide mapping of transcriptional enhancer candidates using DNA and chromatin features in maize
Authors: Rurika Oka, Johan Zicola, Blaise Weber, Sarah N. Anderson, Charlie Hodgman, Jonathan I. Gent, Jan-Jaap Wesselink, Nathan M. Springer, Huub C. J. Hoefsloot, Franziska Turck, Maike Stam
Journal: Genome biology (2017)

While most cells in multicellular organisms carry the same genetic information, in each cell type only a subset of genes is being transcribed. Such differentiation in gene expression depends, for a large part, on the activation and repression of regulatory sequences, including transcriptional enhancers. Transcriptional enhancers can be located tens of kilobases from their target genes, but display characteristic chromatin and DNA features, allowing their identification by genome-wide profiling. Here we show that integration of chromatin characteristics can be applied to predict distal enhancer candidates in Zea mays, thereby providing a basis for a better understanding of gene regulation in this important crop plant. To predict transcriptional enhancers in the crop plant maize (Zea mays L. ssp. mays), we integrated available genome-wide DNA methylation data with newly generated maps for chromatin accessibility and histone 3 lysine 9 acetylation (H3K9ac) enrichment in young seedling and husk tissue. Approximately 1500 intergenic regions, displaying low DNA methylation, high chromatin accessibility and H3K9ac enrichment, were classified as enhancer candidates. Based on their chromatin profiles, candidate sequences can be classified into four subcategories. Tissue-specificity of enhancer candidates is defined based on the tissues in which they are identified and putative target genes are assigned based on tissue-specific expression patterns of flanking genes. Our method identifies three previously identified distal enhancers in maize, validating the new set of enhancer candidates and enlarging the toolbox for the functional characterization of gene regulation in the highly repetitive maize genome.
Scalp Cooling Alopecia Prevention trial (SCALP) for patients with early stage breast cancer.
Authors: Julie R. Nangia, Tao Wang, Cynthia R. C. Osborne, Polly Ann Niravath, Kristen Otte, Steven W. Papish, Frankie Ann Holmes, Jame Abraham, Shari Beth Goldfarb, Jay G. Courtright, Richard Paxman, Mari Rude, Susan G. Hilsenbeck, C. Kent Osborne, Mothaffar F. Rimawi
Journal: Journal of Clinical Oncology (2017)

10088 Background: Adjuvant chemotherapy decreases the risk of recurrence. However, it has distressing side effects, including alopecia. There are no randomized trials assessing modern scalp cooling to prevent alopecia, and success rates in non-randomized trials have varied. Methods: We conducted a multi-center randomized trial to evaluate the safety and efficacy of the Orbis Paxman Hair Loss Prevention System (OPHLPS) in reducing chemotherapy-induced alopecia. Women with stage I-II breast cancer planned to receive anthracycline- or taxane- based chemotherapy for at least four cycles were eligible and randomized in a 2:1 ratio to scalp-cooling or control. Scalp-cooling was done with the OPHLPS 30 minutes prior to, during and 90 minutes after each chemotherapy. The primary efficacy endpoints were hair preservation and device safety. We planned to enroll 235 subjects to provide 85% power to detect a 20% difference in hair preservation. Secondary endpoints included wig/scarf use and quality of life assessed by the EORTC QLQ-30, HADS and BIS. Subjects will be followed for 5 years for recurrence, overall survival, and site of recurrence. One interim analysis was planned to allow the study to stop early for efficacy after 142 subjects were enrolled and evaluable for the primary endpoint. To maintain the overall type 1 error rate, an O’Brien-Fleming spending function was used (interim boundary p = 0.0061). Results: This is the first randomized trial with modern scalp cooling in the world. For the interim analysis, 142 subjects were evaluable. Among them, 48 (50.5%) out of 95 in the cooling group and 0 (0%) out of 47 in the control group had hair preservation. The one-tailed p-value from the Fisher’s exact test is &lt; 0.0001, which crosses the superiority boundary (p = 0.0061). Thus on 9/26/2016 the DSMB stopped the study early. The interim analysis was presented at SABCS 2016. There are 195 subjects enrolled on this clinical trial, and the final subject will be evaluable for the primary outcome February 2017. The final analysis will be presented. Conclusions: Our trial showed that scalp cooling using OPHLPS is highly effective in hair retention. Paxman Coolers has applied for FDA clearance for the OPHLPS based on the results of the interim analysis. Clinical trial information: NCT01986140.
Potential benefits of hypnosis sedation on different modalities of breast cancer treatment
Authors: Martine Berlière, Sarah Lamerant, Philippe Piette, Aurore Lafosse, Laurence Delle Vigne, Fabienne Roelants, Christine Watremez, Marie-Agnès Docquier, Latifa Fellah, Isabelle Leconte, François Duhoux
Journal: Cancer Research (2014)
Intercalated EGFR TKI and chemotherapy induction therapy in EGFR mt+ NSCLC stage IIIA and IIIB: report of 5 cases.
Authors: Frank Griesinger, Julia Roeper, Maria Netchaeva, Anne Christina Lueers, Markus Falk, Imme Selma Conradi, Wilfried Ernst Erich Eberhardt, Cora Hallas, Markus Tiemann
Journal: Journal of Clinical Oncology (2016)

e20059 Background: EGFR TKI treatment is standard of care in metastatic EGFR mt+ NSCLC. Recently new focus has been shed on intercalated regimens of chemotherapy and TKI, showing improved PFS as well as OS. This concept was used as induction regimen in 5 EGFR mt+ pts in stages IIIA/B and is now continued as a phase II study (NeoIntercal). Methods: Patients were diagnosed and worked up according to standard imaging, histology and IHC methods. EGFR, KRAS, BRAF, ALK and P53 mutation analysis were performed by standard procedures. Regression grading was assessed by Junker criteria. Results: 3 f never smokers (pt #1, #3, #5), ages 59, 62 and 62 y, 2 m light smokers (pt#2 and #4) 58 and 69 years had non-squ. NSCLC, 2 with exon 21 L858R (#1,2) and 3 with exon 19 del (#3,4,5). 4/5 patients carried a p53 mutation, disruptive pt #1, non-disruptive pts.#2-4, p53WT #5. Tumor stages were IIIB in pts. #1, 2, 5, IIIA pt. #3, OMD pt. #4. Induction therapy was erlotinib 150 mg/die p.o. (pts #2,3) /gefitinib 250 mg/die p.o. days -12 to -1 (pts #1, 4, 5). On day 0 PR/SD was achieved in 5 pts. Therapy was continued with 3 cycles of taxane /platin based chemotherapy with TKI (erlotinib d4-20 100 mg/ die p.o. or gefitinib 250 mg d4-20 of each cycle). PR was achieved after 2 cycles in all pts. All 5 pts were resected, regression grade IIB was seen in mediastinal lymph nodes (#1-4), regression III was observed in pt #3, IIA in pts #1,2,4 in the primary tumor. Pt. #5 had regression grade I in lymph nodes and primary tumor. All 5 pts received adjuvant mediastinal RTx. All pts are alive for 10+ to 46+ months. Pts #1, 3 and 5 are in CR, pt #2 developed 1 isolated CNS metastasis which was stereotactically irradiated. Pt #4 relapsed systemically with no resistance mechanism and is responding to afatinib. A phase II trial (NeoIntercal) trial is currently under way in 9 German centers in stages II and III using gefitinib in combination with induction taxane based chemotherapy, supported by AstraZeneca Pharmaceuticals. Conclusions: Intercalated TKI treatment is a promising treatment choice in patients with EGFR mt+ locally advanced NSCLC that is pursued in a prospective phase II Trial in Germany.
A Nationwide Analysis of Cost Variation for Autologous Free Flap Breast Reconstruction
Authors: Jessica I. Billig, Yiwen Lu, Adeyiza O. Momoh, Kevin C. Chung
Journal: JAMA Surgery (2017)

<h3>Importance</h3> Cost variation among hospitals has been demonstrated for surgical procedures. Uncovering these differences has helped guide measures taken to reduce health care spending. To date, the fiscal consequence of hospital variation for autologous free flap breast reconstruction is unknown. <h3>Objective</h3> To investigate factors that influence cost variation for autologous free flap breast reconstruction. <h3>Design, Setting, and Participants</h3> A secondary cross-sectional analysis was performed using the Healthcare Cost and Utilization Project National Inpatient Sample database from 2008 to 2010. The dates of analysis were September 2016 to February 2017. The setting was a stratified sample of all US community hospitals. Participants were female patients who were diagnosed as having breast cancer or were at high risk for breast cancer and underwent autologous free flap breast reconstruction. <h3>Main Outcomes and Measures</h3> Variables of interest included demographic data, hospital characteristics, length of stay, complications (surgical and systemic), and inpatient cost. The study used univariate and generalized linear mixed models to examine associations between patient and hospital characteristics and cost. <h3>Results</h3> A total of 3302 patients were included in the study, with a median age of 50 years (interquartile range, 44-57 years). The mean cost for autologous free flap breast reconstruction was $22 677 (interquartile range, $14 907-$33 391). Flap reconstructions performed at high-volume hospitals were significantly more costly than those performed at low-volume hospitals ($24 360 vs $18 918,<i>P</i> &lt; .001). Logistic regression demonstrated that hospital volume correlated with increased cost (Exp[β], 1.06; 95% CI, 1.02-1.11;<i>P</i> = .003). Fewer surgical complications (16.4% [169 of 1029] vs 23.7% [278 of 1174],<i>P</i> &lt; .001) and systemic complications (24.2% [249 of 1029] vs 31.2% [366 of 1174],<i>P</i> &lt; .001) were experienced in high-volume hospitals compared with low-volume hospitals. Flap procedures performed in the West were the most expensive ($28 289), with a greater odds of increased expenditure (Exp[β], 1.53; 95% CI, 1.46-1.61;<i>P</i> &lt; .001) compared with the Northeast. A significant difference in length of stay was found between the West and Northeast (odds ratio, 1.25; 95% CI, 1.17-1.33). <h3>Conclusions and Relevance</h3> There is significant cost variation among patients undergoing autologous free flap breast reconstruction. Experience, as measured by a hospital's volume, provides quality health care with fewer complications but is more costly. Longer length of stay contributed to regional cost variation and may be a target for decreasing expenditure, without compromising care. In the era of bundled health care payment, strategies should be implemented to eliminate cost variation to condense spending while still providing quality care.
Long-term outcomes of laparoscopic distal gastrectomy compared with open distal gastrectomy for clinical stage I gastric adenocarcinoma (KLASS-01): A multi-center prospective randomized controlled trial.
Authors: Hyung-Ho Kim, Sang Uk Han, Min-Chan Kim, Wook Kim, Hyuk-Joon Lee, Seung Wan Ryu, Gyu Seok Cho, Chan Young Kim, Han-Kwang Yang, Do Joong Park, Kyo Young Song, Sang Il Lee, Seung Yub Ryu, Joo-Ho Lee, Woo Jin Hyung, Korean Laparo-endoscopic Gastrointe Group
Journal: Journal of Clinical Oncology (2016)

4060 Background: Laparoscopic distal gastrectomy (LDG) has numerous advantages over open distal gastrectomy (ODG) for defeating gastric cancer. However, there is no direct evidence regarding oncological safety of LDG due to lack of long-term results from phase III randomized controlled trials. Methods: A phase III, multi-center, open-label, non-inferiority, prospective randomized controlled trial comparing LDG with ODG was conducted. The primary endpoint was 5-year overall survival. Inclusion criteria of patients were pathologically-proven gastric adenocarcinoma and preoperative clinical stage I (AJCC/UICC 6th edition). Results: A total of 1416 patients were randomly assigned to laparoscopic group (n = 705) or open group (n = 711) between Jan. 2006 and Aug. 2010. Among them, 1377 patients including 681 laparoscopic group and 696 open group were eligible for intention-to-treat (ITT) analysis. For per-protocol (PP) analysis, 1203 patients, 618 laparoscopic group and 585 open group, were included. By ITT analysis, the 5-year overall survival (OS) rates were very similar in the two groups (95.8% in the laparoscopic group and 95.9% in the open group; log-rank P = 0.774). The lower limit of the 95% confidence interval for the 5-year overall survival rate difference was greater than the pre-specified non-inferiority margin, 5%. The 5-year relapse-free survival (RFS) rates were also similar in the two groups (92.5% in the laparoscopic group and 94.3% in the open group; log-rank P = 0.317). By PP analysis, the 5-year OS rates (96.4% in the laparoscopic group and 96.3% in the open group; log-rank P = 0.929) and the 5-year RFS rates (92.9% in the LDG and 94.7% in the ODG group; log-rank P = 0.368) were also similar in the two groups. Conclusions: The long–term survival after laparoscopic distal gastrectomy is not inferior to that of open distal gastrectomy in clinical stage I gastric cancer. Our study suggests that the laparoscopic distal gastrectomy is an oncologically acceptable alternative to open distal gastrectomy for clinical stage I gastric cancer. Clinical trial information: NCT00452751.
Effect of home-based exercise intervention on fasting insulin and Adipocytokines in colorectal cancer survivors: a randomized controlled trial
Authors: Mi Kyung Lee, Ji-Young Kim, Dong-Il Kim, Dong-Woo Kang, Ji-hye Park, Ki-Yong Ahn, Hyuk In Yang, Dong Hoon Lee, Yun Ho Roh, Ji-Won Lee, Sang-Hui Chu, Jeffrey A. Meyerhardt, Lee W. Jones, Nam-Kyu Kim, Justin Y. Jeon
Journal: Metabolism (2017)
Distinguishing head and neck cancer metastasis from second primary squamous lung cancer in the genomic era.
Authors: Vipul Pareek, Janaki Neela Sharma, Yoko Eng, Steven M. Keller, Richard V. Smith, Xiaoling Guo, Chirag D Shah, Laurie M Gay, Julia Andrea Elvin, James Suh, Jo-Anne Vergilio, Phil Stephens, Jeffrey S. Ross, Vincent A. Miller, Balazs Halmos, Missak Haigentz
Journal: Journal of Clinical Oncology (2016)

e17506 Background: Patients with head and neck squamous cell carcinoma (HNSCC) are at risk for both lung metastases and secondary primary cancers of the lung. Given the histopathologic similarity between these two lesions, distinguishing metastasis from a second primary lung SCC is often based on clinical grounds. Resection of “oligometastatic” HNSCC lesions may be associated with favorable prognosis, although this remains controversial. We demonstrate the potential of a commercially available genomic platform to resolve this clinical dilemma. Methods: A 64-year-old 20 pack-year former smoking male with history of HPV-associated oropharyngeal (OP) cancer 4 years prior presented with an asymptomatic 4.5 cm right hilar mass on surveillance images. Following surgical resection, the patient was referred for adjuvant chemotherapy for pT2aN1 (stage IIB) presumed lung SCC. To settle concerns this was a late recurrence of HNSCC, the primary OP and resected lung tumors were subjected to histopathologic analysis, p16 immunohistochemistry, in situ hybridization (ISH) for HPV 16/18 DNA, and tumor NGS via FoundationOne. Results: Both tumors showed poor differentiation, had strong nuclear and cytoplasmic p16 staining, and were positive for integrated HPV 16/18 by ISH. Comprehensive genomic profiling (CGP) by NGS for both specimens (OP, lung) reported the same somatic mutation in CYLD (K664*; c.1990 A > T) as the sole genomic alteration; moreover, the OP and lung specimens shared 11 of 12 variants of uncertain significance, confirming metastasis from the original OP. The CYLD mutation, present in 6% of HPV-associated HNSCC, results in C-terminal truncation and disruption of CYLD deubiquitinase activity, and is associated with NFκB pathway activation. No chemotherapy was given, and PET/CT imaging 4 months after resection showed no evidence of disease. Conclusions: This is the first report of CGP by NGS to confirm the etiology of secondary squamous lung tumors in patients with HNSCC. In such cases, CGP applied to both primary and subsequent tumors may serve as a fingerprint for distinguishing SCC origin. The role of metastasectomy for treatment deserves additional evaluation.
PTH-012 Preliminary results of a novel temperature controlled endo luminal radio-frequency ablation (elra) electrode for treatment of blocked biliary stents in patients with inoperable pancreaticobiliary cancers
Authors: M Nayar, K Oppong, N Bekkali, J Leeds
Journal: Endoscopy (2017)

<h3>Introduction</h3> Radiofrequency ablation (RFA) has been used in the treatment of blocked biliary metal stents in patients with pancreaticobiliary (PB) tumours with varying results. Complications have been reported with the commonly used probe. This could be related to lack of temperature control and the inability to establish contact with malignant tissue. We report the preliminary results of a novel temperature controlled probe with better tissue apposition for the treatment of blocked biliary stents in PB tumours. <h3>Method</h3> Patients with a confirmed diagnosis of inoperable cancer and a blocked biliary stent were included in this study. Informed consent was obtained for the procedure. ELRA<sup>TM</sup> RFA electrode (Taewoong Medical) was used for the treatment of these patients (Figure 1). The probe is a bipolar electrode with a temperature sensor which helps with controlled ablation and prevents tissue charring. The catheter is 7Fr in diameter (length=175 cms) with an exposure length of 18 mm. Standard protocol was 10 W at 75 degrees administered for 2 min. The procedure was repeated if stricture resolution was suboptimal. Biliary stent was reinserted if necessary to maintain drainage. Immediate and late adverse events and outcomes at 30 days were recorded. <h3>Results</h3> 8 procedures were done on 7 patients (5 males) from April 2016 to January 2017. Aetiology were pancreatic cancer (2); hilar cholangiocarcinoma (2), gall bladder cancer (1), colorectal metastasis (1) and distal cholangiocarcinoma (1). All patients had one prior ERCP procedure. The median length of the stricture was 17 mm (15–25 mm). In 2 patients the procedure was repeated to ensure definitive treatment. One patient had 2 procedures due to a very tight stricture. 5/7 patients required additional stents to ensure optimal drainage. There were no complications and none of the patients have required repeat procedures. Mean follow up period=82.6 days (32 – 225) and 3/7 (43%) patients died due to end stage disease. <h3>Conclusion</h3> This is the first reported data on the use of a novel temperature controlled RFA catheter for the treatment of blocked biliary stents in patients with inoperable PB tumours. The device appears safe and effective; however further randomised trials with long term follow up and larger numbers are required. <h3>Disclosure of Interest</h3> None Declared