tbuckley/cabot-search huggingface dataset:
Ideal Body Mass Index (BMI) difference between curatively resected and metastatic colorectal cancer (CRC) patients on chemotherapy.
Authors: Vincenzo Formica, Stefania Pellicori, Hendrik-Tobias Arkenau, Cristina Morelli, Jessica Lucchetti, Antonella Nardecchia, Silvia Riondino, Patrizia Ferroni, Vittore Cereda, Mario Roselli
Journal: Journal of Clinical Oncology (2015)

e20675 Background: Increased BMI is associated with a higher risk of developing polyps and subsequently CRC. In patients (pts) with curatively resected CRC (crCRC) the relationship between post-surgical BMI and prognosis is unknown and BMI status in metastatic pts (mCRC) is not well established Methods: Between 2006 and 2012 consecutive pts (n = 500) were treated with either adjuvant oxaliplatin/fluorouracil for crCRC (n = 270) or first-line fluorouracil-based chemotherapy for mCRC (n = 230) and evaluated for the relationship between BMI and OS. Kaplan-Meier method with log-rank test and Cox-regression hazard model were used to determine BMI values with favourable prognosis. Smooth flexible hazard ratio curves of BMI were constructed using R 3.1.1 to identify BMI with the best prognosis Results: Percentage of females, median age, 2-year-survival rate (2-y-OS) were 41%, 65(35-85) years, 92% and 41%, 67 (29-85) years, 48% for crCRC and mCRC, respectively. Median BMI was 25 kg/m2 for both crCRC and mCRC, range 15-35 and 15-41, respectively, t-test p value 0.189. In mCRC however there was a direct relationship between BMI and OS, with a 5% increase in the risk of death for 1-unit decrease in BMI (HR 0.95, 95%CI 0.92-0.99, p 0.02), 2-y-OS for the lowest BMI quartile (15-22 kg/m2) vs the highest (29-35 kg/m2), 42% vs 65%, respectively, HR 1.90, p 0.01. In crCRC there was no association between BMI and OS (HR 1.00, 95%CI 0.92-1.07, p 0.90), 2-y-OS for the lowest BMI quartile (15-23 kg/m2) vs the highest (29-41 kg/m2), 97% vs 93%, respectively, HR 0.97, p 0.96. The interaction test between BMI and disease status (crCRC vs mCRC) for OS was significant, p < 0.0001. Gender did not impact on OS and interaction between gender and BMI was not significant for both crCRC and mCRC (p 0.14 and 0.32), respectively. Smooth flexible HR curves revealed that ideal BMI associated with the longest OS in mCRC was > 30 for both males and females Conclusions: In pts with mCRC an increased BMI is associated with improved OS possibly owing to additional energetic reserve counteracting cachexia. Further studies will need to address whether intensified nutritional support to achieve weight gain is warranted to improve OS.
Analysis of inactivation of PI3K/AKT/mTOR signaling pathway using neoadjuvant BKM120 in PI3KCA mutated early breast cancer.
Authors: Estevez G Laura, Suarez Ana, Calvo Isabel, Maria Fernandez Abad, Sofia Perea, Manuel Hidalgo
Journal: Journal of Clinical Oncology (2014)

2611 Background: The PI3K/AKT/mTOR signaling pathway plays a key role for the growth and survival of breast cancer cells and aberrations such as phosphatidylinositol-3-kinase (PIK3CA) mutations are common. BKM120 is an oral pan-class I PIK3CA inhibitor. The aim of this study was to evaluate neoadjuvant BKM120 in PIK3CA mutated early breast cancer in order to assess the effect in PI3K/Akt/mTOR signalling pathway. Methods: Patients (pts) with previously untreated invasive, non-metastatic histologically confirmed breast cancer, with a tumor size ≥ 1,5cm and non-urgent surgical treatment were enrolled. Only women with ER+ / HER2- and PIK3CA gene mutated were eligible. PIK3CA as well as KRAS mutation were evaluated at the diagnosis core biopsy .Patients received treatment with BKM120 (100mg/day; administered orally) during 4 weeks. Subsequently, surgery was performed. Inmunohistochemical analysis of pAkt and pRS6 (the H-score intensity x %) were evaluated on tumor tissue at surgery. H score < 150 was related with inactivation of PI3K signalling pathway. Results: To date 54 patients has been included (median age, 52,5 years; range 38-69 years;). 20 out of 54 (37%) had PIK3CA mutated and 19 have completed BKM120 treatment. PIK3CA mutation: Exon 20, 9 pts; exon 9, 7 pts; exon 4, 2 pts, exon 7, 1 pts and exon 1, 1 pts. None of the tumors had mutations in KRAS at the core biopsy. One patient discontinued treatment due to adverse event (nausea grade 2). The most relevant adverse events included transitory increase of transaminases. No serious or grade 4 adverse events were observed. Preliminary results of 19 pts showed inactivation of pRS6 (H score < 150) in 14 pts (74%) with no change in the reminder 5 pts. Inactivation of pAkt was only observed in 4 out of 11 tumors. Conclusions: Four weeks of neoadjuvant BKM120 produced a noticeable decrease level of the downstream effector pRPS6 in 74% of the tumors. However, decrease level of pAkt was only observed in 4 out of 11 tumors. In our experience, measurement of pAkt in tissue required very stringent conditions for sampling and handling. Thus, assessment of pRS6 seems more reliable and a more appropriate target. Final pAkt analysis will be presented along with updated results. Clinical trial information: CBKM120XES01T.
Outbreak of brainstem encephalitis associated with enterovirus-A71 in Catalonia, Spain (2016): a clinical observational study in a children's reference centre in Catalonia
Authors: D. Casas-Alba, M.F. de Sevilla, A. Valero-Rello, C. Fortuny, J.-J. García-García, C. Ortez, J. Muchart, T. Armangué, I. Jordan, C. Luaces, I. Barrabeig, R. González-Sanz, M. Cabrerizo, C. Muñoz-Almagro, C. Launes
Journal: Clinical Microbiology and Infection (2017)
The Prevention of Gestational Diabetes Mellitus With Antenatal Oral Inositol Supplementation: A Randomized Controlled Trial
Authors: Maria Farren, Niamh Daly, Aoife McKeating, Brendan Kinsley, Michael J. Turner, Sean Daly
Journal: Diabetes Care (2017)

This study investigated if inositol in a combination of myo-inositol and D-chiro-inositol would prevent gestational diabetes mellitus (GDM) in women with a family history of diabetes.This was a randomized controlled trial that examined whether inositol from the first antenatal visit prevents GDM. The trial was carried out in a single-center tertiary referral center. Women with a family history of diabetes were enrolled at the first antenatal visit. They were randomized to the intervention group, which received a combination of 1,100 mg myo-inositol, 27.6 mg D-chiro-inositol, and 400 μg folic acid, or to the control group, which received 400 μg folic acid only. All women had an oral glucose tolerance test between 24 and 28 weeks' gestation. The primary end point was the incidence of GDM. Statistical analysis was carried out using SPSS Statistical Package version 20.Two hundred forty women, 120 in each arm, were recruited between January 2014 and July 2015. There were no differences in characteristics between the groups. The incidence of GDM was 23.3% (n = 28) in the intervention group compared with 18.3% (n = 22) in the control group (P = 0.34). The mean fasting plasma glucose at the glucose tolerance test was 81 mg/dL in both groups.Commencing an inositol combination in early pregnancy did not prevent GDM in women with a family history of diabetes. Further studies are required to examine whether inositol supplements at varying doses may prevent GDM.
U.S. patients receiving resin <sup>90</sup>Y microspheres for unresectable colorectal liver metastases: A multicenter study of 506 patients.
Authors: Andrew S. Kennedy, David Ball, Steven J. Cohen, Michael Cohn, Douglas M. Coldwell, Alain Drooz, Edward Ehrenwald, Samir Kanani, Steven C. Rose, Charles W. Nutting, Fred M Moeslein, Michael Savin, Sabine Schirm, Navesh K Sharma, Eric Wang
Journal: Journal of Clinical Oncology (2012)

3590 Background: Implantation of radioactive microspheres via the hepatic artery with Yttrium-90 ( 90 Y) is termed “radioembolization, (RE)”. Resin microspheres were FDA cleared for use in colorectal liver metastases (mCRC) in 2002. Rapid worldwide acceptance of this therapy has resulted in greater than 30,000 procedures conducted in the past 10 years. This investigator-initiated study focuses on RE treatment outcomes in US-only patients since 2002. Methods: A retrospective multi-institutional study was designed to analyze the outcome of consecutively treated mCRC patients undergoing RE by experienced treatment centers in the USA using resin 90 Y microspheres. IRB approval was obtained by each center with independent data collection and analyses. Primary endpoints: CTC 3.0ae toxicity, RECIST response and survival; baseline treatment parameters, prior chemotherapy, and liver directed therapies. Results: 506 patients at 10 institutions (193 M, 313 F) received 770 RE treatments; median age = 60.4 years (20.8 – 91.9 years); median number of RE treatments per patient = 1.0 (1-5 treatments). Active extrahepatic disease was present at first RE in 34.8% of patients. The majority (90%) of patients received prior chemotherapy, with 30.6% also having undergone prior hepatic surgery/ablative procedures. Median follow up after RE = 8.4 mo. (0.4 – 67.6 mo.) with median survival = 10.1 mo. (95% CI 9.1 – 12.0). For first RE treatment, median tumor volume was 146.0 mL (2.8 – 3228.0 mL). Median radiation activity delivered = 1.18 GBq (0.12 – 2.29 GBq), lung shunt median = 4.8 % (.02 – 45%). Total grade 1-3 events were 32% GI, 44% fatigue and 1% liver failure. Only 2.4% of all treatments required an overnight stay post-procedure. Conclusions: The modern USA experience of 90 Y therapy for unresectable, heavily pretreated mCRC liver metastases is encouraging with a median survival of 10.1 months after first RE procedure. Toxicity was mild and of short duration in most patients. RECIST response is being analyzed currently as are data of additional patients.
First-in-human study of AMG 337, a highly selective oral inhibitor of MET, in adult patients (pts) with advanced solid tumors.
Authors: David S. Hong, Patricia LoRusso, Omid Hamid, Darrin M. Beaupre, Filip Janku, Rabia Khan, Muaiad Kittaneh, Robert D. Loberg, Benny Amore, Isaac Caudillo, Yuying C. Hwang, Rui Tang, Gataree Ngarmchamnanrith, Eunice Lee Kwak
Journal: Journal of Clinical Oncology (2014)

2508 Background: Dysregulation of the MET pathway can promote tumor growth and metastasis, making MET an attractive target for cancer therapy. AMG 337 is an investigational, oral inhibitor of MET kinase activity. This study evaluated the safety, tolerability, pharmacokinetics, and efficacy of AMG 337. Methods: Key eligibility: age ≥ 18 years, advanced solid tumors, measurable disease, ECOG ≤ 2, adequate organ function. AMG 337 was administered orally QD or BID on D1 and D3–28. After 1 week without AMG 337 in the absence of dose-limiting toxicity (DLT) or progression, pts resumed AMG 337 until progression. The starting dose of AMG 337 was 25 mg with planned dose escalation of 50-500 mg QD and 100-200 mg BID (3-9 pts/cohort) until the maximum tolerated dose (MTD, highest dose at which < 33% of pts/cohort had a DLT) was reached or the highest dose was tested. Pts with MET overexpression/amplification/mutation could enroll to the highest dose deemed safe at any time. Results: As of OCT 2013, 66 pts (QD escalation: 3 at 25 mg, 4 at 50 mg, 14 at 100 mg, 9 at 150 mg, 15 at 200 mg, 8 at 300 mg, 6 at 400 mg; BID escalation: 5 at 100mg, 1 at 150mg; expansion: 1 at 300 mg) received ≥ 1 dose of AMG 337. Median age, 59 (19-79) years; men, 56%; ECOG ≤1, 96%. See Table for treatment-related AEs in >10% pts. 8 pts had DLTs: grade (G) 3 headache (150 mg QD, n=1; 200 mg QD, n=2; 300 mg QD, n=1; 400 mg QD, n=2); G3 hypertension (200 mg QD, n=1); G3 increased amylase (400 mg QD, n=1). QD MTD is 300 mg; BID MTD not yet reached. AMG 337 exposures increased with dose, with minimal accumulation after 28 days; half-life, 4.6-7.4 h. Tumor-response data (central read) were available for 45 pts: 1 complete response (CR), 4 partial response (PR), 28 stable disease (SD), 12 progressive disease (PD). Of these, 8 pts had known MET amplification, 7 with gastroesophageal cancer (1 CR [duration of response, 100 weeks], 4 PR, 1 SD, 1 PD) and one with renal cell carcinoma (PD). Conclusions: Responses were observed in a subset of pts with MET-amplified tumors. A dose-expansion phase will enroll up to 50 pts at the MTD (300 mg QD). Clinical trial information: NCT01253707. Grade 1/2 n (%) Grade ≥ 3 n (%) All AEs 34 (51.5%) 17 (26%) Headache 30 (45%) 6 (9%) Nausea 21 (32%) 0 Vomiting 14 (21%) 0 Fatigue 9 (14%) 3 (4.5%) Peripheral edema 8 (12%) 0
Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with advanced cancers of the GI tract and anus.
Authors: Alexa Betzig Schrock, Lauren Young, Samuel Jacob Klempner, Rodolfo Bordoni, Jeffrey S. Ross, Philip J. Stephens, Craig E. Devoe, Fadi S. Braiteh, Siraj Mahamed Ali, Vincent A. Miller
Journal: Journal of Clinical Oncology (2017)

618 Background: The treatment of GI carcinomas (CA) is influenced by the presence or absence of prognostic and predictive genomic alterations (GA). Tissue sampling is the historical platform for genomic biomarker assessment, but non-invasive ctDNA assay provides an alternative when tissue is unavailable or cannot be safely obtained. Methods: Hybrid-capture based genomic profiling using a ctDNA assay (FoundationACT) was performed on blood samples from 82 consecutive pts with lower alimentary canal CA. Results: Median age was 62 (range 28-92) and 61% were male. Anatomic breakdown included CRC (n = 51), esophageal (n = 9), gastric (n = 8), gastroesophageal (n = 3) and small bowel adenoCA (SBA, n = 2), anus squamous cell CA (n = 5), and other GI CA (n = 4). At least one GA was reported in 72% of cases. In 23 cases with no GA reported, the average maximum somatic allele frequency was 0.17% (95% CI: 0-0.6%) vs. 16.7% (95% CI: 0-54.4%) for the 59 cases with GAs (P &lt; 0.0001). For the 3 of 18 patients with both blood and tissue testing performed and samples collected within a 30-day interval, 8/9 (89%) GA detected in tissue were also detected in ctDNA. An average of 1.7 GA/sample were detected in ctDNA. The most commonly altered genes were TP53 (61%), KRAS (24%), BRAF (10%) and PIK3CA (10%). Comparative analysis using the tissue-based Foundation Core database showed a similar trend with overall slightly higher frequencies of GAs in individual genes . RAF and RAS short variants (SV) were exclusive to lower GI and anal CA. KRAS and RAF1 amplification (amp) occurred only in esophageal CA (4/11, 36%). FGFR SV or amp was identified in 3 cases across the cohort. Of CRC, 4 (8%) had ≥ 1 ERBB2 activating SV or amp, 2 (4%) had IDH1/2 hotspot SV, and 2 (4%) had BRCA2 inactivating alterations. ERBB2 activating SV and EGFR amp were found in a SBA and an esophagus CA, respectively. A kinase fusion was identified as the sole driver in 1 CRC ( STRN-ALK) and 1 SBA ( GOPC-ROS1). Outcomes to targeted therapies will be presented for the available subset of patients. Conclusions: Our results provide early clinical support and confirm that hybrid-capture based ctDNA testing can reliably detect all 4 classes of GA and provide a molecular profiling option for patients with GI CA.
Association Between Direct-to-Consumer Advertising and Testosterone Testing and Initiation in the United States, 2009-2013
Authors: J. Bradley Layton, Yoonsang Kim, G. Caleb Alexander, Sherry L. Emery
Journal: JAMA (2017)

Testosterone initiation increased substantially in the United States from 2000 to 2013, especially among men without clear indications. Direct-to-consumer advertising (DTCA) also increased during this time.
A randomized phase II trial of epigenetic therapy following adjuvant treatment in patients with resected pancreatic cancer and high risk for recurrence.
Authors: Kim Anna Reiss, Nita Ahuja, Stephen Baylin, Lauren Ann Mauro, Sheila Linden, Sharon White, Daniel A. Laheru, Joseph M. Herman, Christopher Lee Wolfgang, Matthew J. Weiss, John L. Cameron, Martin Makary, Nilofer Saba Azad
Journal: Journal of Clinical Oncology (2015)

TPS4144 Background: Pancreatic ductal adenocarcinoma (PDAC) has the highest disease specific mortality-to-incidence ratio of any malignancy. Even patients who present with potentially curable disease have a median survival of < 2 years. Those with positive nodes or margins at time of resection or with persistent CA 19-9 elevation have > 90% chance of recurrence despite triple modality therapy. Epigenetic abnormalities in PDAC have been shown to increase malignant proliferation, metastasis and resistance to chemotherapy. Preclinical data has identified a number of specific genes that are commonly hypermethylated in PDAC and have an accompanying phenotypic change leading to a more aggressive tumor, greater chemotherapy resistance and increased epithelial mesenchymal transition. Methylation reversal with a DNA methyltransferase inhibitor (DNMTi) and subsequent gene retranscription has been preclinically demonstrated to result in a less aggressive PDAC phenotype. The effects of DNMTi therapy have been shown to persist even after the DNMTi exposure is removed and may prime for sensitization to chemotherapy, including gemcitabine and taxane therapies. We designed a randomized phase II study of oral 5-azacitidine (CC-486) for patients with resected PDAC and high risk of recurrence (node positive disease, margin-positive resection or rising CA 19-9 following resection). Methods: We have enrolled 11/60 patients. Patients must have completed adjuvant therapy (chemotherapy, radiation or a combination thereof) and have no evidence of recurrence at the time of enrollment. Patients are 1:1 randomized to receive standard-of-care (observation and surveillance) or CC-486 (300mg PO daily for days 1-21 of 28 day cycles) until there is evidence of recurrence. At recurrence, patients have fresh biopsies obtained. Correlative work evaluates for global methylation status as well as for the methylation status of a select group of genes known to be aberrantly methylated in PDAC and whose reversal may be associated with a phenotypic change in tumor behavior. These include: SLIT2/3, ROBO1/2, BRCA1, RAR-B, MGMT, hMLH1, EYA2, p16, RASF1A, FOXE1, NPTX2, Reprimo, ARID1B and Dkk3. Clinical trial information: NCT01845805.
Value of surveillance studies for patients (pts) with stage I-II diffuse large B-cell lymphoma (DLBCL) in the rituximab (R) era.
Authors: Susan M. Hiniker, Erqi L. Pollom, Michael S. Khodadoust, Margaret M. Kozak, Ranjana H. Advani, Richard T. Hoppe
Journal: Journal of Clinical Oncology (2014)

8544 Background: The role of surveillance studies in early-stage DLBCL in the R era has not been well defined. The goal of this study is to evaluate the use of imaging (CT and PET-CT) scans and LDH in surveillance of patients with stage I-II DLBCL. Methods: A retrospective analysis was performed of pts who received definitive treatment (Rx) at Stanford from 2000-2013, using Kaplan-Meier analysis to compute estimates of overall survival (OS) and freedom from progression (FFP). Results: 162 pts with stage I-II DLBCL were treated with R-chemotherapy, radiation (RT), or combined modality therapy (CMT). 5-year OS and FFP were 80.7% and 81.5% respectively. 94/162 pts (58%) achieved a complete metabolic response on PET scan after completion of chemotherapy, and this was associated with superior FFP (HR 3.06, p=0.003). 128/162 pts (79%) were followed with at least one surveillance PET scan beyond end-of-treatment scans. 18/162 pts relapsed after initial response to Rx. Of these, 9 relapses were detected initially by surveillance imaging studies (8 PET, 1 CT), and 9 were detected clinically (5 by pt-reported symptoms, and 4 by both symptoms and physical exam). No relapses were detected by surveillance LDH. At the time of relapse, LDH was found to be elevated in 3/13 pts, all of whom had relapse detected clinically. Median duration from initiation of Rx to relapse was 14.3 mos (range 7.8 – 121.1 mos) among pts with relapses detected by imaging, and 59.8 mos (9.3 – 123.3 mos) among pts with relapses detected clinically (p=0.077). There was no significant difference in OS from date of first Rx or OS following relapse between pts whose relapse was diagnosed by imaging vs clinically. 13/18 pts were successfully salvaged; salvage Rx included chemotherapy alone (10 pts), hematopoietic cell transplant (4 pts), CMT (3 pts) and RT alone (1 pt). Conclusions: A complete response on PET scan immediately after initial chemotherapy is associated with superior FFP in stage I-II DLBCL. Use of PET scans as post-treatment surveillance imaging is associated with earlier diagnosis of relapse, but no OS advantage. LDH is not a sensitive marker for relapse. Our results argue for limiting the use of post-Rx surveillance studies in asymptomatic pts.
Clinicopathologic features and treatment outcome of primary intestinal non-Hodgkin lymphoma: A single center experience.
Authors: Wei-Hsun Hsu, Kun-Huei Yeh, Chung-Wu Lin, Chih-Hung Hsu, Ann-Lii Cheng, Sung Hsin Kuo
Journal: Journal of Clinical Oncology (2013)

e19523 Background: Primary intestinal non-Hodgkin lymphoma (NHL) is a rare but heterogeneous disease in East Asia. However, the benefit of multidisciplinary treatment is still in debate. We characterized the clinicopathologic features, and treatment outcome in a single institute database. Methods: Patients with NHL primarily involving the intestine and treated during 1992 to 2008 were selected from the Cancer Registry of National Taiwan University Hospital. The medical charts and pathology records were carefully reviewed. Results: There were 64 men and 17 women with a median age of 51.5 years. Sites involved were colon/rectum (53.2%), small intestine (30.9%), and duodenum (13%). Histopathology subclassification included diffuse large B-cell lymphoma (DLBCL) (61.7%), mucosa-associated lymphoid tissue lymphoma (11.1%), Burkitt’s lymphoma (8.6%), T cell lymphoma (6.2%), follicular lymphoma (2.5%), mantle cell lymphoma (1.2 %) and others (8.6%). Ann Arbor stage IE to IIE accounted for 61.7%, whereas lower IPI score (1-2) were 54.8%. Among them, 27 patients received surgery plus chemotherapy, 60 received chemotherapy, and 4 had radiotherapy. At average follow-up of 48.7 months, 5 year survival rate were 59%, 43% and 51% for colon/rectum, small intestine, and duodenal NHL, respectively (p=0.45). Surgery plus chemotherapy versus chemotherapy alone showed no survival benefit in lower IPI group (p=0.682) nor in higher IPI (3-5) group (p=0.939). A trend of better median overall survival (mOS) was seen in rituximab group than in non-rituximab group in DLBCL subtypes (not reach vs. 39.8mo, p=0.075). In univariate analysis, stage III/IV (p=0.008), IPI score greater than 2 (p=0.011), and T cell histology (p&lt;0.001) were significant prognostic factors for poor OS. In multivariate analysis, T cell histology remained the independent prognostic factor for inferior OS (p&lt;0.001, HR: 20.3, 95% CI: 5.1-80.4). Conclusions: Although B cell NHL was the majority of primary intestinal NHL in our institute, T cell histology has significant inferior survival. Chemotherapy is still the backbone of treatment for primary intestinal NHL. The benefit of rituximab to intestinal DLBCL needs further confirmation.