tbuckley/cabot-search huggingface dataset:
Optomagnetic imaging spectroscopy (OMIS) as a novel method in the characterization of cervical smears.
Authors: Khalil Razvi, Alexandra Dragicevic, Krishnaswamy Madhavan, Malhotra Anu, Sarah Hemingway, Milena Papic-Obradovic, Djuro Koruga
Journal: Journal of Clinical Oncology (2016)

e23228 Background: OMIS is a novel patented technique that uses optomagnetic spectroscopy principles to discover the differences between the paramagnetic / diamagnetic state of water matter in healthy, pre-cancerous and cancerous tissues with a high degree of accuracy. Using a computerised learning algorithm, a distinction between different cyto-pathological groups is achieved. This system is currently being used under the name TumourTrace. Methods: Archived Liquid Based Cytology samples (132) were selected from 4 main groups: Normal (N), Low Grade (LG), High Grade (HG) and Cancer (C) with 70% used as training sets (TS) to train the algorithm and 30% as a predicting set (PS). All slides with a diagnosis of CIN or cancer had biopsy confirmation to verify the smear result: Normal (N) 23 (TS: 16, PS:7), Low Grade (LG)– Borderline & CIN1 46 (TS:32, PS:14), High Grade (HG)- CIN2&CIN3 35 (TS: 26, PS:9) , Cancer (C) 28 (TS:18, PS:10) Results: 1. OMIS classified Normal and Cancer samples with accuracy of 95%, sensitivity of 100%, specificity of 54%. 2. Classification of Normal and High Grade (CIN2 and CIN3) was with accuracy 89%. Sensitivity was 100%, while specificity was 48% 3. Classification of Normal and Low Grade samples was with accuracy of 74%. Sensitivity was 96%, what means that 1 patient with Low Grade was incorrectly identified as normal, while specificity was 62% what means that 4 normal samples was incorrectly identified as Low Grade Conclusions: This study shows the potential for OMIS to be used as a Point of Care test as an alternative to normal PAP smear testing which does not depend on cytopathology services. The implications for this method of diagnosis in less well resourced economies will be significant.
Exploratory analyses of the BILCAP study.
Authors: John A. Bridgewater, Richard Fox, John Neil Primrose
Journal: Journal of Clinical Oncology (2018)

e16132 Background: The BILCAP study outcome placed adjuvant capecitabine (cape) as the standard of care following curative surgery for biliary tract cancer (BTC). We present exploratory analyses of survival outcome with respect to resection, nodal status and gender. Methods: Patients with completely-resected cholangiocarcinoma (CCA) or gallbladder cancer (including liver and pancreatic resection, as appropriate), with adequate biliary drainage, no ongoing infection, adequate renal, haematological and liver function, and ECOG PS ≤2, were randomized 1:1 to Cape (1250 mg/m2 D1-14 every 21 days, for 8 cycles) or Obs. Randomization was minimized on tumor site, resection status, ECOG PS and surgical center. Overall survival in patient subgroups was explored using Kaplan Meier plots. Planned subgroup analyses tested for heterogeneity through Cox survival models with interaction terms. Results: Planned subgroup analyses revealed no significant heterogeneity in the pre-specified subgroups. However, the observed trends suggest that Cape improves survival in the R0 population, with hazard ratio (HR) favouring Cape 0.73 (95% CI 0.51, 1.04), but less so in the R1 population, with HR 0.90 (95% CI 0.63, 1.29). The local recurrence rate in R1 is 80% with 53% progressing only locally. There is an apparent lack of benefit in peri-hilar CCA, HR 1.08 (95% CI 0.68, 1.71), while extra-hepatic CCA appear to benefit despite a similar R1 rate, HR 0.70 (95% CI 0.47, 1.06). Survival in patients with nodal involvement is considerably worse than for those with negative nodes, with respective 24mo survival of 80% and 50%. The magnitude of benefit from Cape was similar in both groups. It seemed that Cape benefited men, HR 0.70 (95%CI 0.50, 0.99), but less so for women, with HR 0.93 (95%CI 0.64, 1.35). Conclusions: Although not statistically significant, there is a trend for R1 resections, particularly peri-hilar tumors, and women to benefit less from cape. Both node positive and node negative groups benefited from Cape however the overall prognosis for node positive groups was worse. Clinical trial information: 2005-003318-13.
A new prognostic model based on total tumor volume to predict survival rate in locally advanced hepatocellular carcinoma patients.
Authors: Zhan-Hong Chen, Jin-Xiang Lin, Qu Lin, Xing Li, Ying-Fen Hong, Xiang-yuan Wu
Journal: Journal of Clinical Oncology (2017)

e15622 Background: Many HCC patients are diagnosed as locally advanced and loco-regional therapies improved the prognosis of these patients. Survival rates of these patients vary differently. We want to research on the prognostic factors and establish a new prognostic model based on total tumor volume(TTV) to predict the survival rate in locally advanced hepatocellular carcinoma patients who receive loco-regional therapy. Methods: 214 locally advanced HCC patients who received TACE or PEJ were retrospectively studied. Univariate and multivariate analyses were used to assess the variables. A new prognostic model based on TTV was developed with independent prognostic factors. The predictive value was evaluated using receiver operator characteristic curve (ROC) analyses. Results: The median survival is 23.4 months. Univariate and multivariate analyses showed that total tumor volume (TTV), child-pugh garde, protal vein thrombosis and antivirus therapy were independent factors of overall survival. A risk model was establsihed and it is consisted of 4 factors mentioned above. 214 patients were classified into 5 stages by the new staging system. We researched on the predictive value of the new prognostic system by comparing it with CLIP, BCLC and TNM. When predicting 1-year OS, AUC of the new prognostic system, CLIP, BCLC and TNM is 0.620, 0.735, 0.527 and 0.655, respectively; CLIP is best when predicting 1-year os. When predicting 2-year OS, AUC of the new prognostic system, CLIP, BCLC and TNM is 0.623, 0.671, 0.516 and 0.577, respectively;The new prognostic system is as good as CLIP. When predicting 3-year OS, AUC of the new prognostic system, CLIP, BCLC and TNM is 0.623, 0.645, 0.504 and 0.593, respectively; The new prognostic system is as good as CLIP and is better than BCLC(P &lt; 0.05). Conclusions: Total tumor volume is independent prognotic factors of locally advanced hepatocellular carcinoma patients who received locoregional therapies.The new prognostic system based on TTV is as good as CLIP in predicting 2-year OS and 3-year OS. A new prognostic system based on TTV TTV(CM3) &lt; 22.5(0) ≥22.5(1) Antivirus therapy No(0) Yes(1) Child pugh Grade A(0) B(1) Portal vein thrombosis No(0) Yes(1)
Single-center experience with intimal sarcoma, an ultra-orphan, commonly fatal mesenchymal malignancy.
Authors: Julie Van Dievel, Raf Sciot, Marion Delcroix, Raf Vandeweyer, Maria Debiec-Rychter, Barbara Dewaele, Jasmien Cornillie, Thomas Van Cann, Bart Meyns, Patrick Schöffski
Journal: Journal of Clinical Oncology (2017)

e22532 Background: Intimal sarcoma is a rare malignancy that, clinically and radiographically, often mimics pulmonary embolism. The intravascular tumor tends to disseminate rapidly and metastases can be present at first diagnosis. Methods: We reviewed all cases of intimal sarcoma which were diagnosed, treated and followed at the University Hospitals Leuven between April 2006 and April 2016. Results: We identified 13 patients with a median age of 51. In 6 patients initial findings were suggestive of thromboembolic disease. PDGFRA amplification was the most prevalent molecular finding, present in 11 patients. The MDM2 gene was amplified in 9 cases, the EGFR gene in three patients. The median overall survival was 13 months. Eleven patients underwent surgery. In 5 cases with inoperable and/or metastatic disease chemotherapy was given. Treatment with imatinib was initiated in 4 patients. Conclusions: Intimal sarcoma is an extremely rare and aggressive malignancy that has a very poor prognosis. Mimicking thromboembolic disease, diagnosis and treatment can be delayed. Surgery is the mainstay of treatment but is seldom curative. The disease is highly resistant to cytotoxic and targeted treatment. Given the fact that intimal sarcoma commonly expresses more than one molecular target, combination therapy might be an option, though toxicity may be a limitation.
Immunotherapeutic approaches for soft-tissue sarcoma: Augmentation of natural killer cell cytotoxicity by <i>e</i>x-vivo expansion and use of an anti-GD2 antibody.
Authors: Veit Buecklein, Tobias Jorg, Desiree Pass, Christina Krupka, Patrick Schlegel, Peter Lang, Hans Hoffmeister, Lars Lindner, Wolfgang Hiddemann, Marion Subklewe
Journal: Journal of Clinical Oncology (2016)

e14528 Background: Patients with advanced soft-tissue sarcoma (STS) have a poor prognosis with high relapse rates. Immunotherapeutic strategies aim to eradicate quiescent malignant cells as origin of relapse. Tumor-induced immunotolerance leads to dysfunction of Natural Killer (NK) cells in different cancers. Restoring NK cytotoxicity by ex vivo expansion and directing NK cells to the tumor by use of tumor antigen-specific antibodies might be synergistic strategies to convey anti-tumor immunity. Methods: We compared the NK cytotoxicity of STS patients with that of healthy donors (HD) in a 51Cr release assay against K562 cells. NK cell expansion and augmentation of cytotoxicity were evaluated after long-term culture in an Interleukin 2-containing bioreactor, and expression of NK cell antigens was analyzed by flow cytometry. Additionally, effects of ch14.18, an antibody against GD2 (an antigen frequently expressed on STS) on NK cytotoxicity were tested against sarcoma cell lines with diverging GD2 expression (TC-71, SW872, SKUT-1). Results: Patient NK cells showed impaired cytotoxicity against K562, whereas lytic activity against STS cell lines was minimal for both patient and HD NK cells. Expansion of NK cells of patients (n = 4) and HD (n = 3) resulted in cell counts of up to 90-fold of baseline, and led to a significant increase (up to 25-fold) in cytotoxicity against K562 and STS cell lines. Patient NK cells showed altered expression of NK cell receptors (e.g. NKp46, CX3CR1) compared to HD NK cells, and expression of activating receptors (e.g. NKG2D) was upregulated after expansion. Addition of ch14.18 resulted in increased cytotoxicity of unstimulated NK cells of healthy donors and patients against GD2-expressing STS cell lines of up to 7-fold. For expanded NK cells of healthy donors, no additional effect of ch14.18 was seen. Conclusions: NK cells of STS patients show impaired cytotoxicity. Reconstitution of their lytic activity might be a promising immunotherapeutic strategy. Bioreactor-based long-term cell expansion and use of anti-GD2 antibodies are complementary approaches to stimulate anti-STS cytotoxicity in vitro and warrant further evaluation.
MGMT promoter methylation status testing to guide therapy for glioblastoma: refining the approach based on emerging evidence and current challenges
Authors: Alireza Mansouri, Laureen D Hachem, Sheila Mansouri, Farshad Nassiri, Normand J Laperriere, Daniel Xia, Neal I Lindeman, Patrick Y Wen, Arnab Chakravarti, Minesh P Mehta, Monika E Hegi, Roger Stupp, Kenneth D Aldape, Gelareh Zadeh
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is the most common primary malignant brain tumor, with a universally poor prognosis. The emergence of molecular biomarkers has had a significant impact on histological typing and diagnosis, as well as predicting patient survival and response to treatment. The methylation status of the O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter is one such molecular biomarker. Despite the strong evidence supporting the role of MGMT methylation status in prognostication, its routine implementation in clinical practice has been challenging. The methods and optimal cutoff definitions for MGMT status determination remain controversial. Variation in detection methods between laboratories presents a major challenge for consensus. Moreover, consideration of other clinical and genetic/epigenetic factors must also be incorporated into treatment decision making. In this review, we distill the available evidence to summarize our position on the optimal use of available assays, and propose strategies for resolving cases with equivocal methylation status and a framework for incorporating this important assay into research and clinical practice.
Abstract 12809: Abnormal P-Wave Axis is Associated With an Increased Risk of Ischemic Stroke: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Ankit Maheshwari, Faye L Norby, Elsayed Z Soliman, Wesley T O’Neal, Alvaro Alonso, Lin Y Chen
Journal: Circulation (2016)

Introduction: Abnormal P-wave axis (aPWA) has been linked to incident atrial fibrillation (AF) and mortality; however, the relationship between aPWA and stroke has not been reported. Hypothesis: We hypothesized that aPWA is associated with ischemic stroke independent of AF and other stroke risk factors and tested our hypothesis in the Atherosclerosis Risk In Communities (ARIC) study, a community-based prospective cohort study. Methods: We included 15,102 participants (age, 54.2 ± 5.7 yrs, 55.2% women, 26.5% blacks) who attended the baseline exam (1987-89) and without prevalent stroke. We defined aPWA as any value outside 0-75 degrees using 12-lead ECGs obtained during the baseline exam. Incident ischemic stroke was identified by annual phone interviews, hospital discharge records, and death certificates. Each case was classified in accordance with criteria from the National Survey of Stroke by a computer algorithm and adjudicated by physician review. Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of aPWA with stroke. Results: During a mean follow-up of 20.2 years, there were 1027 incident ischemic stroke cases. aPWA was independently associated with a 1.37-fold (95% CI, 1.11-1.69) increased risk of ischemic stroke in the multivariable model. After further adjustment for AF, aPWA remained independently associated with a 1.30-fold (95% CI,1.05-1.61) increased risk of ischemic stroke. Conclusions: aPWA was independently associated with ischemic stroke. This finding suggests that abnormalities in atrial electrical activation are associated with ischemic stroke independent of AF.
Preliminary safety and activity of perioperative triplet chemotherapy plus bevacizumab (bev) in patients with borderline resectable colorectal cancer liver metastases (CLM).
Authors: Alessia Mennitto, Christian Cotsoglou, Marta Caporale, Mauro Scotti, Rosa Berenato, Jorgelina Clara Coppa, Maria Di Bartolomeo, Massimo Milione, Ilaria Bossi, Filippo G. De Braud, Vincenzo Mazzaferro, Filippo Pietrantonio
Journal: Journal of Clinical Oncology (2016)

e15031 Background: FOLFOXIRI and bev achieve high response rate/R0 resections and encouraging PFS in patients with unresectable CLM. Pathological response, a surrogate endpoint of survival, is increased by bev. COI-B (capecitabine, oxaliplatin, irinotecan and bev) is a feasible regimen in pts with advanced colorectal cancer. In this phase II study, we aimed at assessing the perioperative use of this combination in pts with borderline resectable CLM (NCT2086656). Methods: Inclusion criteria: borderline resectability due to technical (need of 2-stage hepatectomy, involvement of > 1 hepatic vein or > 4 segments) and/or biological reasons ( > 4 metastases, CEA > 200, synchronicity). Limited resectable extraepatic disease and in situ primary allowed. Primary endpoint: pathological response according to Rubbia-Brandt et al., with a Simon 2-stage design (first step 22 pts; target 46 pts); secondary endpoints: objective response rate (ORR); R0 resection; safety; progression-free and overall survival. Pts received biweekly irinotecan (180 mg/mq) and bev (5 mg/kg) day 1, oxaliplatin (85 mg/mq) day 2 and capecitabine 1000 mg/mq day b.i.d.) days 2-6; 5 cycles pre-operatively (the last without bev) and 4 post-operatively. Results: we present preliminary data on the first 29 pts (26 resected, 3 still awaiting). M/F: 17/12, median age 57 years (38-76), synchronous disease 79%, multiple nodules 55%, N+ primary tumor (69%), CEA > 200 14%, extrahepatic disease 0.03%, RAS mutation 59%/no BRAF mutation. Two-stage hepatectomy 0.04%, ≥ 4 segments involved 34%, > 1 hepatic veins 14%. ORR was 89% (24/27 restaged patients), with 2 SD and 1 PD. R0 resection in 22 (85%) resected pts. TRG 1-2 was observed in 8 (31%), while TRG 3 in 12 (46%), i.e. pathological response rate 77% (first step reached). Grade ≥ 3 toxicities: diarrhea 2, neutropenia 2, thrombosis 2, neuropathy 1, fatigue 1. At a median follow up of 16 months, only 7 relapses and 2 deaths were observed. Conclusions: COI-B regimen is a feasible neoadjuvant strategy for borderline resectable CLM. This is the first trial to select pathological response as primary endpoint with encouraging activity. Clinical trial information: NCT2086656.
Statistical significance of bevacizumab trials when considering the portfolio of all studies.
Authors: Derrick L Tao, Nathanael D. Gay, Vinay Prasad
Journal: Journal of Clinical Oncology (2018)

6551 Background: Although clinical trials of novel medications have historically been interpreted individually, there is increasing recognition that trials should be considered as part of a broader clinical trials agenda or portfolio. If a single drug is tested in many tumor types, the interpretation of any single trial result must account for the number of times that agent is trialed. We attempted to better understand the effect of the trials portfolio for bevacizumab, an antibody approved in many tumor types. We conducted a systematic review of cancer trials of bevacizumab efficacy when added to a chemotherapy backbone in solid tumors and adjusted results for the number of reported trials. Methods: We queried MEDLINE for “solid tumor”, “bevacizumab” and “meta-analysis” on 2/2/2018, extracting all included randomized controlled trials, their reported improvement in median progression free survival (PFS), overall survival (OS), and accompanying p values. We investigated 1. What percent of individual studies met traditional nominal statistical significance for PFS and OS and 2. What percent retained this significance after adjusting for multiplicity using the Bonferroni correction, a commonly used method. Results: Our search identified 3 meta-analyses, including 48 randomized trials, 47 reported PFS and OS data. Of the 48 trials, 8 (17%) were phase II and 40 (83%) were phase III. Most common tumor types among the 48 trials included colorectal (14; 29%) and breast (9; 19%). A statistically significant PFS benefit (using a p < .05 cutoff) was reported in 30 of 47 trials (64%). After adjusting the p-value for multiplicity using the Bonferroni correction (P < .00106), 21 trials reported statistically significant improvements (45%). A statistically significant OS benefit (using P < .05) was reported in 7 of 47 (15%) trials. After adjusting p-value for multiplicity using the Bonferroni correction (P < .00106), 1 trial (2%) reported statistically significant improvement. Conclusions: The number of statistically significant studies of bevacizumab is reduced when corrected for multiplicity, suggesting that the current analytic plans may overestimate clinical benefit and could benefit from portfolio-based analysis.
Single nucleotide polymorphisms within Mucin-type O-glycan genes are associated with colorectal cancer survival.
Authors: Shun Lu, Calogerina Catalano, Stefanie Huhn, Barbara Pardini, Veronika Vymetalkova, Ludmila Vodickova, Kari Hemminki, Asta Foersti
Journal: Journal of Clinical Oncology (2018)

e15607 Background: Secreted mucins form the physical barrier which play an important role dor maintaining gut homeostasis, while transmembrane mucins contribute to the protective mucous gel. Dysregulation of mucin biosynthesis, especially of Muc2, and loss of core 1 and core 3-derived O-glycans have been shown to induce colitis and CRC in murine models. Intriguingly, loss of core 3 synthase (encoded by the B3GNT6 gene), which plays an important role in the synthesis of mucin-type O-glycans in digestive organs, has also been shown to lead to development of colon cancer in a mouse model. Single nucleotide polymorphisms (SNPs) in the promoter or other regulatory regions may regulate the expression of these genes, or affect the function of the coded protein. Methods: Altogether 123 SNPs were covered by the 23 SNPs genotyped in the MUC1, MUC2, MUC4, MUC5AC, MUC6, and B3GNT6 genes in a hospital-based case-control study of 1532 CRC cases and 1108 healthy controls from the Czech Republic. Moreover, we also analyzed overall survival both in the 672 CRC patients diagnosed between 2003 and 2013 and in a subgroup of 494 patients with non-metastatic disease at the time of diagnosis, using the date of death or last contact with the treating physician as the end point of follow-up. The effects of different genotypes on overall or event-free survival were evaluated using Kaplan-Meier method and they were compared using log-rank testing. Prognostic significance was evaluated using Cox proportional hazard models. Results: We found only one MUC6 5’UTR SNP was nominally associated with the risk of CRC (OR 0.78, 95%CI 0.64-0.96, p = 0.02). In the survival analysis among patients without distant metastasis at the time of diagnosis, two MUC4 SNPs showed associations with overall survival (HR 1.40, 95%CI 1.08-1.82, additive model, log-rank p = 0.004 and HR 0.64, 95%CI 0.42-0.99, recessive model, log-rank p = 0.01, respectively) and event-free survival (HR 1.31, 95%CI 1.03-1.68, log-rank p = 0.004 and HR 0.64, 95%CI 0.42-0.96, log-rank p = 0.006, respectively). Conclusions: Our data suggest that genetic variation especially in the transmembrane mucin MUC4 may play a role in the survival of CRC and further studies are warranted.