tbuckley/cabot-search huggingface dataset:
Systematic review of response evaluation in gastrointestinal stromal tumors
Authors: S. Verma, B. Macdonald
Journal: Journal of Clinical Oncology (2009)

e21500 Background: Our purpose was to conduct an evidence-based systematic review of the literature on the accuracy of 18FDG PET - CT(PET) and contrast enhanced computer tomography (CT) in assessment of response to imatinib therapy in advanced gastrointestinal stromal tumor (GIST) Methods: A systematic review of the literature between January 2000 and December 2008 was performed on Medline and EMBASE. Inclusion criteria included prognostic studies or diagnostic studies using CT or PET to determine response to imatinib. Only articles with Level 1B or higher were included. The following variables were extracted: imaging modality (PET, In-line PET/CT, CT), response criteria used EORTC,RECIST criteria, or novel criteria), and the clinical outcome (time-to-treatment failure (TTF), time to progression (TTP), progression free survival (PFS), disease specific survival (DSS), and/or overall survival). The number of responders and non-responders was extracted from the data, and the reported log rank statistics for the Kaplan Meier curves were used to determine the strength of correlation between the responders and the clinical outcomes. Results: Five articles met the strict criteria for Level 1B evidence. Four articles met the inclusion criteria for In-line PET/CT. In these four articles the log rank correlation between In-line PET/CT response criteria described by the EORTC and the outcome measure of TTF ranged between. p=0.002 -0.04, a very high degree of positive correlation. A subset of four articles met the strict methodological inclusion criteria for CT using RECIST criteria. The log rank correlation for RECIST ranged from p=0.100 - 0.74, no significant correlation. Only one of the articles met the criteria for prospectively applying novel CHOI criteria with CT in a validating cohort. The log rank correlation with the TTF was p=0.0002, a very high degree of positive correlation. Conclusions: In-line PET/CT using EORTC criteria accurately predicts the response to imatinib in terms of TTF or PFS across four Level 1B studies. CT using RECIST criteria has a poor correlation with TTF in well designed studies and is not a useful predictor of response; consistently poor across four Level 1B studies. CT using CHOI criteria shows promise in a single Level 1B study No significant financial relationships to disclose.
KIT gene molecular analysis distinguishes multiple primary GIST from metastatic disease
Authors: A. P. Dei Tos, S. Rossi, D. Gasparotto, I. Bearzi, G. Gallina, R. Maestro
Journal: Journal of Clinical Oncology (2007)

10048 Background: The occurrence of multiple primary GIST (MPG) has been reported exclusively in children and in NF1 patients. However, sometimes adult GIST patients present at onset with double lesions raising the problem of the differential diagnosis between metastatic and MPG. Morphologic features might help in recognizing MPG. A clear cut distinction is much less obvious when dealing with simultaneous high risk lesions. Molecular analysis of KIT gene may represent an important tool to discriminate among these two possibilities, allowing proper therapeutic strategies. Methods: From a series of 200 GIST we selected 5 non NF1 adult GIST patients, presenting double lesions at onset. Genomic DNA was extracted from both the nodules of each patients and exons 9, 11, 13, 14 and 17 of KIT gene were sequenced. Cases were also investigated for KIT exon 10 and intron 10 and PDGFRA exons 12 and 18. Results: Age ranged from 48 to 82 years. Four patients had a dominant nodule, ranging in size between 3 and 10 cm, and a peritoneal/hepatic nodule ranging in size between 0.8 and 3 cm. One patient had one gastric and one small intestinal nodules of 6 cm. No significant differences in mitotic rate and morphology were seen between the two nodules in each case. In two cases, both nodules showed same molecular profile, confirming the metastatic nature of the disease. In one case, the same KIT mutation was detected in both lesions, but an additional mutation was present only in the intestinal tumor. In contrast, in one case, different KIT mutations were found, suggesting the occurrence of two synchronous GIST. In an additional case, while a PDGFRA mutation was found in the tumor located in the stomach, no mutations were detected in the tumor located in the liver. Conclusions: 1. Molecular analysis proves the existence of exceptional cases of multiple primary GIST in non children, non NF1 patients. 2. Since discrimination between metastatic disease at onset and multiple primaries impacts over therapeutic strategies, it might be useful also in the routine practice to perform molecular analysis of both nodules in cases of double GIST. No significant financial relationships to disclose.
Correlation of epidermal growth factor receptor (EGFR) mutation profile with computed tomography (CT) imaging features in lung adenocarcinomas.
Authors: Benjamin F. Chu, Efe Ozkan, Selnur B Erdal, Weiqiang Zhao, Konstantin Shilo, Gregory Alan Otterson
Journal: Journal of Clinical Oncology (2013)

7542 Background: Imaging studies provide essential clinical information for lung cancer diagnosis, treatment and management. Features such as ground glass opacity (GGO) or internal air bronchogram (IAB), while commonly seen in early stage lung cancer, have minimal clinical implication. By examining a cohort at a single institution, we explored the hypothesis that radiographic characteristics correlates with the molecular signatures. Methods: Since 2009, our institution has prospectively characterized the EGFR status of all non-squamous lung carcinomas. Our inclusion criteria included tumor size &lt; 3 cm and positive EGFR mutation. We randomly selected wild type (WT) patients matched by age and tumor size. The CT imaging of these patients was evaluated by a single radiologist (EO). Results: Imaging features were extracted from 20 WT and 19 EGFR-mutated tumors. Of the EGFR-mutated tumors, 7 had the exon 21 L858R point mutation and 12 had in-frame exon 19 deletion. There were 68% (13) solid nodules in EGFR-mutated and 90% (18) in WT tumors. While solid nodule was the primary feature seen in both WT and EGFR-mutated tumors, exon 21 mutation was associated with mixed ground glass/solid nodule (MGGS) (p = 0.005). This tendency, however, is not present in the exon 19 mutated tumors. No pure GGO was identified in either EGFR or WT group. IAB was present in 62% (24), pleural attachment (PA) in 87% (34), and spiculated (SP) as opposed to lobulated (LO) nodules in 90% (34) of the tumors, which do not differ significantly among groups. Conclusions: Early stage lung adenocarcinomas show a spectrum of imaging features that can be correlated with tumor’s genetic mutations. MGGS is a distinct imaging characteristic differentiating exon 19 and exon 21 EGFR-mutated tumors. [Table: see text]
Outcome of interventions to identify family history and risk management for women with breast cancer in the ambulatory setting
Authors: N. J. Washburn, S. Simmons, V. Sommer, B. Adkins, P. Gerken, M. Rogers, B. Wilson, B. Lang, B. Hickman, C. Barnhart, S. Ethirajan
Journal: Journal of Clinical Oncology (2006)

6121 Background: In 2002, Kansas City Cancer Center (KCCC) performed a quality improvement (QI) project to evaluate how breast cancer patients were being assessed for family history and cancer risk management. A self-administered family history questionnaire was developed to improve the thoroughness of family history collected and education of clinicians was completed to improve the recognition of risk factors based on ASCO guidelines. Methods: Chart audits on 210 women with breast cancer at KCCC, were completed in the second quarter of 2005. All patients were under the age of 65, not undergoing chemotherapy. A risk management tool was developed. Scoring criteria for 2002 was replicated in 2005 as listed in the table . Results: In 2002, 171 pts (89%) had level 1 or 2 family history assessed compared to 207 pts (99%) in 2005, p&lt;0.0001. In 2002, 47% had 3 generations assessed compared to 84% in 2005, p&lt;0.0001. In 2002 and 2005, some risk factor management occurred in both groups, and was equal, 78% and 80% respectively (p=ns). Of those that had risk management 33% had level 1 in 2002 compared to 3% in 2005 (p&lt;0.0001) a 91% reduction in identifying risk without subsequent management. In 2002, 58% had level 2, compared to 71% in 2005 (p=0.02) a 23% improvement in identification &amp; management of risk. In 2002, 9% had level 3 compared to 26% in 2005 (p&lt;0.0001) a 183% improvement in patients with a detailed risk assessment and/or genetic referral. Conclusions: By improving the assessment of family history and education of providers, women with breast cancer are receiving more information to reduce their risk for recurrence and complications. Patients who were identified as high risk for BRCA1 or BRCA2 mutations were referred to either a nurse practitioner or genetic counselor. [Table: see text] No significant financial relationships to disclose.
Synthetic miRNA Switch Technology Elucidates Heterogeneity in Regulation of Immortalized Megakaryocyte Cell Lines, Associated with Improvement of Platelet Generation Efficiency for Clinical Use
Authors: Kazuya Hashimoto, Satoshi Matsuura, Yoshihiko Fujita, Karin Hayashi, Naoshi Sugimoto, Takuya Yamamoto, Hirohide Saito, Koji Eto
Journal: Blood (2016)
Impact of interferon-γ release assay on the latent tuberculosis cascade of care: a population-based study
Authors: David Z. Roth, Lisa A. Ronald, Daphne Ling, Leslie Y. Chiang, Victoria J. Cook, Muhammad G. Morshed, James C. Johnston
Journal: European Respiratory Journal (2017)

Latent tuberculosis infection (LTBI) screening and treatment can have a significant impact on TB incidence if a high proportion of at-risk people successfully complete an adequate course of LTBI therapy [1–5]. Patient loss and dropouts occur at multiple points along the LTBI screening and treatment process, ultimately resulting in a minority of high-risk people completing LTBI therapy. To understand the public health impact of new screening and treatment strategies, we need to evaluate the impact of various interventions on the LTBI cascade of care. Sequential TST–IGRA testing may reduce LTBI therapy and improve treatment completion without increasing active TB <http://ow.ly/2Kzr307W1tm>
Phase I study of nivolumab (nivo) + <i>nab</i>-paclitaxel (<i>nab</i>-P) ± gemcitabine (Gem) in solid tumors: Interim results from the pancreatic cancer (PC) cohorts.
Authors: Zev A. Wainberg, Howard S. Hochster, Ben George, Martin Gutierrez, Mark Emery Johns, E. Gabriela Chiorean, Eunice Lee Kwak, Aparna Kalyan, Victoria Manax, Moncy Ye, Tianlei Chen, Nataliya Trunova, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2017)

412 Background: Immune checkpoint inhibitors, such as nivo, an anti−PD-1 antibody, have demonstrated antitumor activity in various cancers. Chemotherapy has demonstrated immune system activation via multiple mechanisms, providing a rationale for combination approaches. nab-P + Gem is a standard of care in PC which does not require immunosuppressive corticosteroids. Here we report interim results from 2 PC cohorts (Arms A and B) of a phase I study in patients (pts) receiving nivo + nab-P ± Gem for locally advanced or metastatic PC. Methods: This 2-part study was designed to identify dose-limiting toxicities (DLTs) of nivo + nab-P ± Gem in Part 1 and assess tolerability and efficacy in Part 2 dose expansion (+ Gem). Pts were DLT evaluable if they received ≥ 2 cycles of treatment and remained on study for 14 days after last dose or discontinued due to a DLT prior to completing 2 cycles. After Arm A, Part 1 was deemed safe, Arm B, Part 1 was initiated. In Arm A, pts with 1 prior chemotherapy regimen received nab-P 125 mg/m 2 on days 1, 8, and 15 of a 28-day cycle (qw 3/4) + nivo 3 mg/kg on days 1 and 15 of a 28-day cycle starting with cycle 1. In Arm B, treatment-naive pts received the same regimen in Arm A + Gem 1000 mg/m 2 qw 3/4. Results: As of June 28, 2016, 11 and 6 pts were treated in Arms A and B in Part 1, respectively. No DLTs were reported in Arm A, and 1 in Arm B (nonimmune hepatitis, suspected to be due to Gem; resolved and pt continued nivo + nab-P without Gem). The most common grade 3/4 teatment-emergent AEs were pulmonary embolism, neutropenia, and anemia in 2/11 pts (18%) in Arm A and anemia in 2/6 pts (33%) in Arm B. Nine patients discontinued due to progressive disease (8 in Arm A, 1 in Arm B). Best overall response is shown in the Table. Median treatment duration was 12.6 and 15.5 weeks for Arms A and B, respectively. Clinical trial information: NCT02309177. Conclusions: These results indicate that adding nivo to nab-P ± Gem is feasible for pts with advanced PC, and antitumor activity of this regimen appears to be encouraging. Based on promising results from Part 1, Arm B, Part 2, is enrolling pts.[Table: see text]
Combined whole genome copy number genotyping and multiplex somatic mutation profiling of FFPE brain tumor specimens for clinical diagnosis and trial selection.
Authors: Brian Michael Alexander, Shakti Ramkissoon, Patrick Y. Wen, David A. Reardon, Eudocia Quant Lee, Mikael Rinne, Andrew David Norden, Lakshmi Nayak, Sandra Ruland, Lisa M. Doherty, Debra C. LaFrankie, Loreal E Brown, Nils D. Arvold, Ian F. Dunn, Sandro Santagata, Barrett J Rollins, Neal Ian Lindeman, Rameen Beroukhim, Azra Ligon, Keith L. Ligon
Journal: Journal of Clinical Oncology (2013)

2030 Background: Multi-dimensional cancer genotyping is increasingly needed for clinical diagnostics and trial selection. Whole genome copy number is relevant for glioblastoma and other brain tumors but routine prospective FFPE-based multiplex copy number and somatic mutation genotyping for clinical trials has not been achieved. Methods: Using novel DNA extraction protocols we implemented whole genome copy number (Agilent aCGH stock 1M feature arrays) and somatic mutation profiling (Oncomap v4.4 Sequenom) assays into a CLIA-certified laboratory setting. Twenty-three copy number aberrations (CNAs) relevant to brain tumors were reported from whole genome data and Oncomap results were reported for 471 cancer-related mutations in 41 genes. Results: During the initial eight months of our combined copy number and mutation-testing program, aCGH and Oncomap were performed prospectively on 239 and 157 brain tumor patients respectively. Copy number was reported in 90% of patients (214/239) and failures were due to insufficient DNA from small biopsies. GBMs (n = 94) harbored gains and losses at expected rates and included amplifications of common drug targets (EGFR, EGFRv3, MET, MDM2, MDM4, PDGFRA, CDK4, CDK6). Emerging candidate drug targets were identified including variant EGFR deletions (e.g. EGFRv2) and FGFR3-TACC3 gains for which other clinical tests are not available. Oncomap results for 78 GBMs revealed mutations in TP53, PTEN and IDH1. Less frequent mutations occurred in BRAF, RB1, PIK3CA, PIK3R1 and KRAS. We integrated copy number and mutation data for 27 GBMs, allowing for improved evaluation of tumor suppressor inactivation status (e.g. PTEN mutation with monosomy 10). In combination, our assays reported data on 10 clinically actionable drug targets relevant for 15 clinical trials open at the time of patient testing. Conclusions: We implemented complementary assays for efficiently detecting genome-wide CNAs and mutations on FFPE brain tumor samples in a CLIA-certified environment. Systematic integration of these results broadens the range of diagnostic and actionable data available to identify patients for trials of targeted therapeutics.
Salvage surgery (SS) versus elective surgery (ES) after chemoradiotherapy (CRT) for locally advanced esophageal cancer
Authors: K. Tsutsumi, H. Udagawa, Y. Kinoshita, M. Ueno, S. Mine, Y. Kajiyama, M. Tsurumaru
Journal: Journal of Clinical Oncology (2004)

4176 Background: Definitive CRT and neoadjuvant CRT followed by esophagectomy are accepted treatments for locally advanced esophageal cancer. SS for local failure of CRT is an option for selected patients (pts), but the morbidity is reported to be high. Methods:We investigated 126 pts receiving CRT for locally advanced esophageal cancer between 1995 and 2002 to clarify the value of SS versus ES and the prognostic factors for esophagectomy after CRT. Among them, 67 pts received definitive CRT (>60Gy) alone, 11 pts underwent CRT plus salvage surgery (SS Group), 48 pts underwent ES with neoadjuvant CRT of 30∼40 Gy (ES Group). Accordingly, 59 pts underwent CRT followed by esophagectomy (CRTS Group ). Results: There were no significant differences of clinical characteristics, response rate, pathological response rate, adverse effects, number of dissected nodes and metastatic nodes, and grade of residual tumor after surgery between SS and ES. The percentage of pts having esophagectomy with D0 (no lymph node dissection) and non curative resection was higher in the SS Group (37.5% and 36.3% respectively) than the ES Group (8.3% and 16.7%). Morbidity was higher in the SS Group (90.9%) than the ES Group (66.7%). Particularly, anastomotic leakage was more common in SS pts (36.3%) than ES pts (12.5%) (p=0.057). Median survival was 853 days in the SS Group and not significantly different from the ES Group (641 days). Distant metastasis was the most frequent failure in both groups. The clinical response was not a significant prognostic factor for CRTS, but the pathological response was significant in univariate analysis (p=0.0284). The residual tumor grade and morbidity had independent prognostic significance for CRTS in multivariate Cox proportional hazards model analysis. Conclusions: SS after local failure of CRT is a useful option for selected pts without distant metastasis, possible curative resection, and a good response to CRT, whereas definitive CRT causes increased morbidity. No significant financial relationships to disclose.
Analysis of PDL1 expression and T cells infiltration in 1014 gastric cancer patients.
Authors: Xiaofang Xing, Ziyu Li, Jiping Wang, Jiafu Ji
Journal: Journal of Clinical Oncology (2017)

50 Background: Although immune checkpoint inhibitors have demonstrated promising results in melanoma and lung cancer, their effects on gastrointestinal cancer are still under investigation. Understand the prognostic effect of PDL1 expression, infiltration by CD8+ and CD3+ T cells in gastric cancer (GC) might help the identification of candidate patient who might benefit from immunotherapy. Methods: Immunohistochemistry were performed on a tissue microarray including 1,014 GC specimens with PD-L1 antibodies. Immune cell markers CD3 and CD8 were also stained and the quantitative differences were calculated using automated image analysis. Results: 37.8% of the cases showed a membranous PD-L1 expression in tumor cells and 74.9% in tumor infiltrating immune cells. GC patients with high level PDL1 expression in tumor cells or in immune cells were both associated with better survival compared with those with negative expression (5-year OS, 61% vs. 48%, P = 0.000, and 55% vs. 45%, P &lt; 0.0001, respectively). As continuous variables, higher CD3+ and CD8+ cell density were associated with patients’ overall survival and the associations remained as the significant prognostic factors that predict favorable outcomes even after adjusting other unknown confounding factors.(HR: 0.974, 95%CI: 0.963-0.985, P = 0.000; and HR: 0.973, 95%CI: 0.960-0.986, P = 0.000 for CD3 and CD8 respectively). We also observed the close relationship between CD3+, CD8+ cell density and PDL1 expression both in tumor cells and in infiltrating immune cells. Conclusions: This study indicates that PDL1 expression, and TILs in particular, are important prognostic biomarkers. Patients with higher CD8 and CD3 T cell densities also have higher PD-L1 expression, indicating an adaptive immune resistance mechanism may be occurring. The counterintuitive observation that higher PD-L1 expression associating with better patients’ outcome highlights the need to assess both PDL1 expression in all tumor compartments and the characterization of the GC immune microenvironment.
Analysis of overall survival and safety during the course of the phase III VELOUR trial comparing FOLFIRI and ziv-aflibercept or placebo in mCRC patients who progressed on prior oxaliplatin treatment.
Authors: Paul Ruff, Radek Lakomy, Jana Prausová, Guy A. Van Hazel, Vladimir Moiseyenko, Joseph McKendrick, Emmanuelle Boelle, Remi Castan, Teresa Macarulla, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2013)

3574 Background: VELOUR, a large, international, randomized, placebo (pbo)-controlled study, compared efficacy and safety of FOLFIRI with ziv-aflibercept (known as aflibercept outside the United States) or with pbo in 1,226 metastatic colorectal cancer patients who received prior oxaliplatin treatment. Ziv-aflibercept demonstrated statistically significant, clinically meaningful improvements in median overall survival (OS) (13.5 vs 12.06 mos; hazard ratio [HR]=0.817, P=0.0032), progression-free survival, and response rate. This analysis estimates treatment effect and safety over time course of the study. Methods: HRs by 6-mo time periods were estimated using piecewise Cox proportional hazard model. NCI-CTCAE v3.0 was used to grade adverse event (AE) severity. Results: HR improved over time (Table), consistent with survival curves that continue to separate past the median time point, indicating that the magnitude of ziv-aflibercept treatment effect continues to increase over time. Incidence of grade 3 AEs (45.1% vs 62.0%) was higher in the ziv-aflibercept/FOLFIRI arm; incidences of grade 4 AEs were 17.4% (pbo) vs 21.4% (ziv-aflibercept). More common AEs only occurred in a small proportion of ziv-aflibercept/FOLFIRI cycles (eg, grade ≥3 hypertension and diarrhea occurred in 3.6% and 2.8% of cycles, respectively). The majority of grade 3/4 AEs occurred in early treatment (first 3-4 cycles). Most patients experienced only a single episode of grade ≥3 AEs with ziv-aflibercept/FOLFIRI. Importantly, AEs in VELOUR did not impact patients’ ability to receive chemotherapy. Conclusions: Treatment with ziv-aflibercept/FOLFIRI showed continuous, consistent improvement in OS over time. While combined grade 3/4 AEs were higher with ziv-aflibercept, AEs occurred early in treatment in a small proportion of total cycles; the majority were single-episode in nature. Clinical trial information: NCT00561470. [Table: see text]